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Beyond Heat Stress: Intestinal Integrity Disruption and Mechanism-Based Intervention Strategies

Puqiao Lian, Saskia Braber, Johan Garssen and 4 more

Nutrients · 2020 · Review · CC BY

doi:10.3390/nu12030734

Abstract

The current climate changes have increased the prevalence and intensity of heat stress (HS) conditions. One of the initial consequences of HS is the impairment of the intestinal epithelial barrier integrity due to hyperthermia and hypoxia following blood repartition, which often results in a leaky gut followed by penetration and transfer of luminal antigens, endotoxins, and pathogenic bacteria. Under extreme conditions, HS may culminate in the onset of “heat stroke”, a potential lethal condition if remaining untreated. HS-induced alterations of the gastrointestinal epithelium, which is associated with a leaky gut, are due to cellular oxidative stress, disruption of intestinal integrity, and increased production of pro-inflammatory cytokines. This review summarizes the possible resilience mechanisms based on in vitro and in vivo data and the potential interventions with a group of nutritional supplements, which may increase the resilience to HS-induced intestinal integrity disruption and maintain intestinal homeostasis.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 23, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

1The gastrointestinal (GI) tract is the largest surface of the body that is in contact with the outside environment. The intestinal epithelium is regarded as a physical and biochemical barrier between the luminal commensal and pathogenic microbial communities and the mucosal immune system. Dysfunction of this barrier is caused by various pathological, toxicological, and physical stressors, including heat stress (HS), leading to local or systemic inflammatory reactions. Severe intestinal epithelial damage is considered as a major factor involved in HS-associated mortality. The GI tract is affected by HS due to the thermoregulatory mechanism of the body shifting visceral blood flow towards the peripheral circulation to facilitate heat dissipation. This leads to visceral ischemia, followed by hypoxia, in visceral organs such as the intestines. Recent investigations unraveled the susceptibility of different organs to high body temperatures, demonstrating that the observed multi-organ failure is induced by a combination of heat-induced cytotoxicity, coagulopathies, and a systemic inflammation that affects not only the GI tract, but also other key organs and tissues, including the central nervous system, the kidneys, the liver, and the muscle tissue. HS-induced hypoxic conditions in the intestine result in disturbance of the balance between the production of reactive oxygen species (ROS) and the antioxidant defense system, leading to epithelial damage and an inflammatory response (Figure 1). Intestinal hypoxia can also induce local inflammation via barrier-independent pathways, involving cellular acidification by glycolysis, activation of autophagy and protective innate immune responses elicited by hypoxia-inducible factor (HIF)-1α.

2HS has also been reported to negatively impact on production animal physiology, in particular poultry. Modern poultry genotypes allow rapid growth but is also linked to higher metabolic activity and reduced heat tolerance. This increased susceptibility of chickens to HS leads to multiple pathophysiological alterations also seen in humans, for example, intestinal barrier disruption and inflammation, oxidative stress responses and microbiome changes. Considering the relevance of HS-induced cellular oxidative stress, disruption of intestinal integrity and the local and systemic inflammatory responses in humans and animals (poultry), the main aim of this review is to discuss promising nutritional intervention strategies, which may increase HS tolerance and to discuss their mechanisms of action, possibly explaining their beneficial effects in maintaining and supporting the intestinal homeostasis.

2.1. Heat Shock Response (HSR)

3The heat shock response was initially described as a specific molecular response of cells to adapt to elevated temperature. Later, various environmental and pathophysiological stressors, which cause protein aggregation or misfolding, were found to induce a similar reaction. HSR is regulated by the activation of a family of interacting transcription factors, the so-called “heat shock factors (HSF)”, of which HSF1 is the best-characterized factor that is essential for the HSR. Under physiological conditions, HSF1 is bound to heat shock proteins (HSP) in a monomeric form. Upon activation by cellular stressors, this complex of HSF1 and HSP dissociates and leads to trimerization and translocation of HSF1 into the nucleus and initiates the transcription of more HSP (Figure 2a). HSP fulfil an important role in binding to and protecting misfolded cellular proteins, a typical sign of HS. Among the variety of HSP family members, HSP70 is considered as the most stress-responsive protein, which is usually expressed at low basal levels and increases in response to stressors to protect the cells from proteotoxic damages by binding to damaged proteins and contributing to the refolding of unfolded or misfolded proteins. Subsequently, HSP inhibit apoptosis and even more important, the inflammatory response.

2.2. HSR and Oxidative Stress Response

4Cell survival largely depends on the balance between ROS and cellular antioxidant mechanisms. The high reactivity of ROS can modify several cellular macromolecules, such as nucleic acids, proteins, and lipids. HS is a potent inducer of ROS production, which leads to tissue damages as soon as the cellular redox defense system, consisting of glutathione (GSH), glutathione peroxidase, superoxide dismutase (SOD), and haem oxygenase 1 (HO-1), is exhausted. Hyperthermia can provoke ROS production by adversely affecting mitochondrial membrane integrity and their electron transport chains, but is also able to hamper the antioxidant defense system directly. The expression of the antioxidant system is mainly regulated by nuclear factor erythroid 2 related factor 2 (Nrf2), which is repressed in the cytoplasm by the regulatory protein Kelch-like ECH-associated protein 1 (Keap1) under physiological conditions. Dissociation of Nrf2 from Keap-1 upon oxidative stress, leads to translocation of Nrf2 to the nucleus where it binds to the ARE to induce the transcription of antioxidant proteins improving cell survival under stress conditions (Figure 2b).

5Local hypoxia caused by HS-induced changes in blood flow (from visceral to peripheral circulation) is identified as another major cause of ROS production. The main cellular response to hypoxia is triggered by HIF. Under normal conditions, the α subunit of HIF is rapidly hydroxylated by oxygen-sensitive prolyl hydroxylases (PHD) and then degraded in the proteasome. However, under hypoxic conditions, PHD activity is inhibited, leading to HIF-1α stabilization and transcriptional activity so that cells can adapt to the hypoxic stress. One consequence of hypoxic signaling is the abnormal accumulation of ROS by complex III of the mitochondrial electron transport chain. ROS generated under hypoxic conditions in turn contribute to HIF-1α stabilization and activate the oxidative stress response via Nrf2, as previously discussed.

2.3. Resilience Pathways and Intestinal Barrier Integrity

6Expression of HSP, in particular HSP70, is associated with the stabilization of the actin cytoskeleton of intestinal cells, preventing their aggregation under stress conditions. Elevated levels of HSF1 and HSP70 are crucial in increasing the expression of actin fibers in epithelial cells of the GI tract. Upon activation under HS conditions, HSF1 binds to the occludin promoter region mediating the upregulation of the expression and improving the participation of occludin in junctional complexes. Exogenous HSP70 added to cell cultures prevents HS-induced alteration in permeability. We recently showed that one of the possible mechanisms by which the antioxidant α-lipoic acid (ALA) and the amino acid arginine preserve the intestinal integrity under HS conditions could be related to the enhancement of HSP70 expression. A possible mechanism by which HSP70 attenuates the epithelial barrier dysfunction under stress conditions will be through preventing the activation of conventional protein kinase C (cPKC), thereby reducing the myosin light chain (MLC) protein phosphorylation of the actin cytoskeleton. Another member of the HSP family, the Apg-2 (a member of the HSP110 subfamily), interacts directly with zonula occludens protein-1 (ZO-1), regulating the transcriptional activity of ZO-1-associated nucleic acid binding protein. The upregulation of HSP70 in Caco-2 cells (human epithelial colorectal adenocarcinoma cell line) following exposure to gliadin is associated with a redistribution of HSP70 towards the cytoskeleton, which improves the action of HSP70 in the maintenance of intestinal barrier function by allowing direct interaction with junctional proteins such as ezrin and E-cadherin.

7Nrf2-Keap1 regulation is also linked with preserving intestinal barrier integrity. Jin et al. observed higher intestinal permeability and plasma levels of endotoxin in the Nrf2-/- mice compared with wild-type mice in a traumatic brain injury-induced intestinal mucosa damage model. The upregulation of AhR-Nrf2 pathway and its target gene HO-1 (also known as HSP32) expression enhances the barrier function in the mice with inflammatory bowel diseases (IBD). Moreover, the extracellular signal-regulated kinase (ERK)/Nrf2/HO-1 signaling pathway can prevent the intestinal barrier damage by mediating mitophagy and increasing the expression of tight junctions (TJ) proteins under hypoxic conditions. Interestingly, Nrf2 has two binding sites on the upstream of claudin-4 DNA sequence in the esophageal epithelium, highlighting the importance of Nrf2 in the TJ regulation.

2.4. Resilience Pathways and Immune System

8Translocation of xenobiotics and bacterial products, following intestinal epithelial damage under HS conditions, may evoke an inflammatory response, which results in exaggeration of intestinal barrier dysfunction. The anti-inflammatory properties of HSP70 have been studied extensively in chronic inflammatory disorders, such as IBD and celiac disease, as well as under conditions of hyperthermia. The upregulation of HSP70 in response to HS is involved in the inhibition of pro-inflammatory cytokine expression. HSP block the production of pro-inflammatory cytokines by inhibiting the translocation of Nuclear Factor-κB (NF-κB) to the nucleus. Van Eden reviewed the effect of HSP on expansion of anti-inflammatory regulatory T cells (Treg) and concluded that the introduction of HSP inducers into the diet can be considered as a therapeutic approach against inflammatory disorders. This specificity of HSP is not limited to endogenous (self) HSP, since administration of bacterial HSP is also an effective strategy in treatment of immune-challenging disorders. Anti-inflammatory mechanisms of HSP are beyond the scope of this review and a more complete description of these mechanisms is presented in different review articles.

9The crosstalk between ROS and Nrf2 and/or NF-κB, which activates the inflammatory cascade, is very complex and not yet fully elucidated. Nrf2 and HSF1 regulate overlapping target genes and may compensate for each other. HO-1 is considered as the most important Nrf2 target gene in facilitating NF-κB inhibition, which can be regulated by HSF1 as well. Additionally, exposure of HSF1 mutant cells to HS stimulates (although with delay) the upregulation of HSP70 and HO-1, which is mediated by Nrf2.

10Nrf2 also regulates intestinal immune function by affecting T cell polarization. The activation of Nrf2 inhibits the secretion of the Th1 cytokine IFNγ and interleukin (IL)-2 in early events, thereafter promoting CD4+ Th2 differentiation. Moreover, Keap1 itself seems to be involved as a positive regulator of NF-κB in inflammatory signaling.

11In conclusion, activation of both the heat shock and oxidative stress responses contribute to an increased resilience to heat stress conditions and may help to mitigate the stressful effects of increased body temperature and decreased oxygen accessibility by regulating the expression of protective proteins, such as HSP, Nrf2, and HO-1. HSP, Nrf2 and HO-1 in the intestinal epithelia can interact with junctional complexes and components of the immune system resulting in the restoration of local homeostasis following hyperthermia and hypoxia.

3. Intervention Strategies against HS

12As mentioned earlier, hyperthermia and subsequent hypoxia not only provoke ROS production, but also directly hamper the antioxidant defence system.

13Independent from these direct effects on cells of the intestinal barrier system, the gut microbiota is a common target of HS conditions. Alterations in the composition of the gut microbiota, together with the HS-induced impairment of the barrier function, increase the likelihood of opportunistic intestinal infections. In turn, pre- and probiotics have gained recent interest, as they are able to stabilize the intestinal microbiota under stress conditions. A variety of antioxidant substances, fatty acids, and selected amino acids are also commonly recommended to mitigate disease conditions closely associated with cellular oxidative stress, as will be discussed below.

3.1. Microbiota Modulation

14The gut microbiota, which comprises a vast array of microorganisms, has a key effect on the regulation of host nutrition and metabolism, as well as on the stimulation of gut maturation, development, proliferation, and immune homeostasis. A variety of host conditions, including diet, immune reactions, infections, and usage of antibiotics influences the gut microbiota. Stress conditions, including HS, induce alterations in the microbiota balance, which may result in the colonization of enteric pathogens, and intestinal inflammatory responses. Stabilization of the gut microbiota composition by pro-, pre-, syn-, and postbiotics is considered as an effective strategy to improve gut health and to protect the intestines against stress conditions.

3.1.1. Probiotics

15Probiotic bacteria are defined as “living microorganisms which exert health promoting benefits when administered in adequate amounts”. A large range of bacteria are considered as probiotics, while the most common strains belong to Lactobacillus and Bifidobacterium species. While probiotics were initially identified based on the competitive displacement of pathogens, they have also shown to be protective against non-infective disorders, such as dextran sodium sulfate (DSS)-induced colitis in mice, and influence the morphology and the immunological homeostasis in the GI tracts of animals and humans. Furthermore, the beneficial effects of probiotics are related to the improvement of different components of the gut barrier system, including the regulation of immune reactions, and enhancement of intestinal epithelial cell integrity.

16A clinical study showed that four weeks of daily supplementation with a probiotic mixture containing strains of Lactobacillus, Bifidobacterium, and Streptococcus species maintains the intestinal integrity and reduces the penetration of LPS into the blood in male runners affected by intense exercise-induced HS. Furthermore, supplementation with a matrix and six probiotic strains (B. bifidum, B. lactis, E. faecium, L. acidophilus, L. brevis, and L. lactis) for 14 weeks reduced the concentration of zonulin in feces of athletes, and improved intestinal barrier integrity. It is known that increased zonulin concentration in feces is related to enhanced gut permeability and changes in tight junction competency. Moreover, in vitro evidence demonstrated that a mixture of three different strains of Lactobacillus species increased trans-epithelial electrical resistance (TEER) values, occludin mRNA expression, and mucus production in Caco-2:HT29–MTX epithelial co-cultures. Model experiments in broiler chickens indicate that probiotics successfully alleviate the detrimental effects of HS on the microstructures of the small intestine, such as reduced villus height and density. An ex vivo study from Song et al. showed that 42-day treatment with a L. plantarum, B. licheniformis, and B. subtilis mixture could restore the decreased trans-epithelial electrical resistance (TEER) levels and subsequently increased the paracellular permeability in the jejunal segment of HS-exposed chickens. The beneficial effects of this probiotic mixture was associated with an increase in occludin and ZO-1 protein expression.

17Bacilli are also commonly used as human probiotics for their multi-bioactivity and high bio-safety. Feed supplementation with B. subtilis for 42 days improves the intestinal integrity in chickens by increasing the expression of occludin, claudin-2, and claudin-3 in the jejunum and the ileum. Similarly, pretreatment of B. subtilis for two days diminishes the intestinal morphological changes and bacterial translocation as well as lipopolysaccharides (LPS) penetration to the blood flow in rats exposed to HS.

18Probiotics do not only interact with the bacterial populations in the intestine, but there is also an interplay between microbiota and the host’s defense system. For example, probiotics directly and/or indirectly modulate different signaling pathways that regulate the intestinal integrity, including Rho family GTPases, protein kinase C (PKC), and mitogen-activated protein kinase (MAPK). The protective effect of a Gram-negative E. coli Nissle probiotic on intestinal integrity of T84 cells (colonic adenocarcinoma epithelial cells) challenged by enteropathogenic E. coli, is related to the stabilization of ζ isotype of protein kinase C (PKCζ), thereby preventing the phosphorylation and dissociation of ZO-2 from the TJ network. In agreement with these findings, the epithelial barrier function in T84 cells is enhanced by the four strains of Gram-positive probiotic Lactobacillus species via their effect on adherens junctions (AJs), including E-cadherin and β-catenin, by reducing the abundance of δ isotype of protein kinase C (PKCδ) in membrane junctional complexes, highlighting the notion that probiotics with different Gram-staining status target distinct signaling pathways regulating different intercellular junctions. L. brevis produces a bioactive molecule, polyphosphate, through activation of the integrin–p38 MAPK pathway, which leads to increased HSP expression at protein level and prevention of oxidant-induced intestinal barrier disruption. In addition, the protective effects of the probiotic strains of S. thermophiles and L. acidophilus on occludin phosphorylation in human intestinal epithelial cells challenged with enteroinvasive E. coli, can be inhibited by a Rho kinase inhibitor.

19The probiotic B. licheniformis supports the gut mucosal immunity in broiler chickens exposed to HS, by preventing HS-induced increase in pro-inflammatory cytokines and decrease in intraepithelial lymphocytes, the IgA secreting plasma cells and mucin production. B. subtilis B10 stimulates the mucosal immunity development in broiler chickens by increasing IgA secretion and mRNA expression of the anti-inflammatory cytokine IL-10. Furthermore, clinical studies showed that dietary supplementation with a probiotic mixture increases the post-exercise plasma concentrations of IL-10 in exercise-induced HS.

20The immune-regulatory properties of probiotics have been studied extensively in treatment of diseases affecting the intestinal mucosal immunity, such as IBD. It seems that the mechanism by which probiotics exert anti-inflammatory properties, is through inhibition of NF-κB. Moreover, probiotics stimulate CD103+ dendritic cells to produce IL-10 and IL-27 via the toll-like receptors (TLR)-2/MyD88 pathway.

21Overall, probiotics modulate both the innate system (via natural killer cells, dendritic cells, macrophages, epithelial cells, and granulocytes) and the adaptive system (Th1, Th2, Th17, Treg, Tc, and B cells). The activation of an innate immune response by probiotics is mainly facilitated by microbe-associated molecular patterns, including bacterial cell wall polysaccharides and peptidoglycan, which interact with TLR, C-type lectin receptors, and nucleotide oligomerization domain-like receptors. However, it should be taken into account that as yet no single probiotic is found to exert all the above-mentioned effects.

3.1.2. Prebiotics

22Dietary prebiotics are described as “selectively fermented ingredients that result in specific changes in the composition and/or activity of the GI microbiota, thus conferring benefit(s) upon host health”. Human milk oligosaccharides (HMO), a major component of colostrum, represent the first prebiotic in the human diet. A recent study confirmed the protective action of HMO by supplementing neonatal mice formula and media for Caco-2 cells, and found an improved response against hypoxia-induced injuries. Various attempts have been made to design alternative prebiotic oligosaccharides that mimic the health promoting effects of HMO, including galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS), which are widely used in infant formulas. These non-digestible oligosaccharides are not hydrolyzed by mammalian digestive enzymes and reach the distal intestines, where they modify the autochthonous microbiota and exert a beneficial effect on the gut microbiota. Selective stimulation of beneficial bacteria, such as Lactobacillus and Bifidobacterium species, can induce immunomodulatory effects, enhance the intestinal integrity and preserve the intestinal micro-structures. The gut microbiome targets different intracellular pathways via fermentation of non-digestible oligosaccharides and the subsequent production of short chain fatty acids (SCFA), such as acetate, propionate, or butyrate. The postbiotic, butyrate, increases the antioxidant glutathione and decreases ROS production when applied directly to the human colon cells, which would probably modulate the HS-induced intestinal damage by ROS. Moreover, SCFA, such as propionate and butyrate, activate free fatty acid receptor (FFAR) 2 [also known as G-protein-coupled receptor (GPR) 43] and FFAR3 (GPR41) to stimulate the mucus secretion and facilitate the production of anti-inflammatory cytokine IL-10.

23In vivo investigations in chickens exposed to HS have shown that supplementation of the diet with mannan-oligosaccharides (MOS) and cello-oligosaccharides (COS) mitigated the heat-induced changes in intestinal morphology and intestinal barrier function. Furthermore, MOS enhance the intestinal integrity by increasing villus height, the number of goblet cells, and the populations of lactobacilli and bifidobacteria, while at the same time reducing the E. coli load in the ceca of chickens. HMO incubated with B. longum infantis increased IL-10 expression and ZO-1, occludin and junctional adhesion molecule (JAM)-A mRNA transcription in Caco-2 and HT-29 cells. In turn, an in vitro experiment reported that FOS improved the viability and heat tolerance capacity of two strains of lactobacillus species: L. plantarum and L. acidophilus. Chitosan oligosaccharides attenuate inflammatory infiltrates and epithelial degeneration in mice colon, and increase TEER in T84 cells. Our group showed that dietary GOS supplementation diminishes the disruption of intestinal integrity by preventing the alterations in TJs and AJs in the jejunum of broiler chickens exposed to HS. In addition, GOS increase the number of intestinal bifidobacteria in rats and play a key role in prevention of intestinal integrity disruption by increasing the mRNA and protein expression of occludin.

24Besides the effects on the gut microbiota, microbiota-independent effects and direct interactions of these oligosaccharides with different (immune) cells have raised more attention in recent years. FOS was found to directly promote barrier integrity by increasing ZO-1 and occludin expression, through a protein kinase C (PKC) δ-dependent mechanism, in pathogen-challenged Caco-2Bbe1 cells (a Caco-2 subclone) and human intestinal organoids. Our in vitro investigations highlighted the effect of GOS on direct regulation of the intestinal integrity and junctional complexes to prevent the disruption of intestinal integrity induced by HS. Moreover, pre-treatment with GOS prevents the disruption of intestinal integrity by accelerating TJ reassembly and stabilizing the expression and cellular distribution of claudin-3 TJ protein in Caco-2 cells. The microbiota-independent effect of non-digestible oligosaccharides on intestinal epithelial integrity depends on the oligosaccharide structure, size, and concentration. Although further research is needed to unravel the exact mechanism involved in the direct regulation of intestinal integrity by oligosaccharides, an in vitro study with T84 cells showed that chitosan oligosaccharides promote TJ assembly by activating 5' adenosine monophosphate-activated protein kinase (AMPK) through calcium-sensing receptor-phospholipase C-IP3 receptor channel-mediated calcium release.

25We showed in broiler chickens that dietary GOS prevents the HS-induced mRNA upregulation of IL-6 and IL-8 in the jejunum. This effect could be related to the GOS-preserved intestinal integrity. In addition, GOS prevent the HS-induced TLR-4 upregulation in the jejunum. Disruption of intestinal integrity followed by translocation of luminal antigens and pathogens through the intestinal epithelium exaggerates TLR signaling, facilitates immune responses, and eventually leads to the development of intestinal inflammation and intestinal injury. Another study from Wang et al. also showed that by reducing the expression of TLR-4 and NF-κB, and accelerating the turnover of crypt cells, HMO protect intestinal epithelial cells from necrotizing enterocolitis (NCE) injury in mice. Additionally, TLR-4 is described as a stress-related biosensor in the initial injury responses and may contribute to the intestinal barrier disruption, since it is demonstrated that TLR-4 knockout mice are protected from HS-induced intestinal hyper-permeability and microvascular endothelial barrier dysfunction.

26In recent years, the immune-regulatory effects of prebiotics to prevent intestinal disorders, such as IBD and NCE, (food) allergy, or intestinal damage related to mycotoxin exposure are extensively studied. GOS suppress the mycotoxin-induced increase in CXCL8 in Caco-2 cells as well as the murine CXCL8 analogues (CXCL1 and CXCL2) in the intestine. Moreover, dietary GOS mitigate the inflammation-induced expression of the alarmin IL-33 in two different murine models. Jeurink et al. reviewed the different mechanisms which can underlie the immune effects of dietary oligosaccharides.

27In summary, pro- and pre-biotics exert their therapeutic and prophylactic effects on HS-induced intestinal integrity disruption by modulating immune function, improving gut barrier integrity by stimulating mucus production and modulating junctional proteins, increasing antioxidative capacity, and supporting the resident microbiota. The effects of pro- and pre-biotics on intestinal integrity and immunomodulation are summarized in Table 1.

3.2. Antioxidants

28Preserving the redox balance, by the participation of Nrf2 and Keap1, is crucial to control the overproduction of ROS and maintain intestinal integrity under HS conditions.

29ROS are signaling molecules in physiological levels but are also responsible, at a high concentration, for intracellular damage. Under physiological ROS production levels, proteinaceous antioxidants act as a defence mechanism to neutralize ROS production. However, conditions such as HS are associated with excessive ROS generation. Therefore, supplementation with oral exogenous antioxidant components or pro-oxidants, which can beneficially trigger the Nrf2-Keap1 pathway, may help to alleviate oxidative stress and its contribution to the pathogenesis of HS in the intestine.

3.2.1. α-Lipoic Acid (ALA), a Fatty Acid with Antioxidant Properties

30ALA is synthesized from octanoic acid in the mitochondria and is present in pro- and eukaryotic cells, being identified as a potent cellular antioxidant. Both reduced and oxidized forms of ALA retain the antioxidant potency by scavenging free radicals, exhibiting metal chelating activity, and through their involvement in redox regeneration of other antioxidants (vitamin C and E). ALA is used as treatment for diverse pathologies associated with redox imbalances, including diabetes, ischemia-reperfusion injury, and heavy metal poisoning. However, ALA may act as mild pro-oxidant by slightly increasing ROS concentrations to activate Nrf2 and HSF, and therefore increasing the resilience to stress conditions. In addition to redox-regulating effects, ALA may enhance gut integrity and exert anti-inflammatory properties. ALA hampers the disruption of intestinal integrity and modulates the intestinal inflammation in models of HS, post-weaning diarrhea and ulcerative colitis.

31Although the intestinal integrity-associated effects of ALA are not extensively studied under HS conditions, investigations in Caco-2 cell monolayers exposed to HS showed that ALA prevents the disruption of intestinal integrity by maintaining protein expression and distribution of the AJ, E-cadherin. Furthermore, ALA stimulates proliferation of intestinal epithelial monolayers and facilitates the reassembly of TJs.

32ALA supplementation preserves the intestinal integrity in oxidative and inflammatory disorders associated with intestinal damage. ALA stimulates the recovery of the intestinal epithelial architecture by increasing transcription and translation of occludin and ZO-1 TJ proteins in a rat model for post-weaning diarrhea. These findings are confirmed by in vitro studies with IEC-6 intestinal epithelial cells. ALA mitigates the intestinal morphological damage by preventing the decrease in villus height and increase in crypt depth in glycinin-induced anaphylactic reactions in rats. Additionally, ALA co- and post-treatment decreases ulcerative colitis-induced gut permeability by maintaining the expression of occludin in mice. These effects are, at least in part, related to the regulation of the redox balance since oxidative stress induces a tyrosine-kinase-dependent dissociation of E-cadherin-β-catenin and occludin-ZO1 complexes, which leads to their cellular redistribution and a loss of barrier integrity. Additionally, the pro-oxidant activity of ALA stimulates the transcriptional activity of HSF1 to induce the expression of HSP70. HSP70 may be involved in the maintenance of barrier integrity through direct interaction with TJ proteins and stabilizing the junctional complexes.

33The anti-inflammatory effects of ALA are closely related to its antioxidant properties. As mentioned before, activation of the NRF2 transcription factor by ALA results in the induction of HO-1, which exerts anti-inflammatory effects by degrading intracellular haem to free ion, carbon monoxide and biliverdin. In the last decade, the effect of ALA in the transcriptional regulation of genes associated with inflammatory pathways were highlighted. Exposure of Caco-2 cells to HS increases cyclooxygenase-2 (COX-2) mRNA expression, the inducible COX, which is attenuated by ALA pre-incubation. COX-2 catalyses the rate-limiting step in the conversion of arachidonic acid into inflammatory prostaglandins. Interestingly, inhibition of COX-2 by ALA is speculated to be important in the prevention of ulcerative colitis in rats. ALA, co- and post-treatment in mice with ulcerative colitis, not only prevents the transcription of COX-2, but also significantly reduces various inflammatory markers, such as myeloperoxidase, IL-17, IL-6, and TNF-α in the colon.

34These findings support the hypothesis that the anti-inflammatory and protective effects of ALA under stress conditions are mainly attributable to the inhibition of IκB/NF-κB phosphorylation, hence preventing the activation of NF-κB.

3.2.2. Resveratrol, a Plant Polyphenol Compound

35The polyphenolic compound resveratrol (3,5,4′-trihydroxytrans-stilbene) is present in grape skin, grape seeds, and peanuts. Resveratrol is an important bioactive compound, which displays a strong antioxidant and anti-inflammatory capacity. The significance of resveratrol in ameliorating the deleterious effects of HS has been reviewed previously. Indeed, enhancing resilience to oxidative stress via administration of antioxidants or pro-oxidants (compounds which moderately induce the ROS just enough to activate the antioxidant defence system) has been introduced as an effective strategy in preventing HS-induced gut-associated dysfunction.

36Although the exact underlying mechanism between the antioxidant capacity of resveratrol and the protective effect on gut homeostasis is not fully understood, the induction of HSP, in particular HSP70, HSP90, and HO-1, is one of the major effects of resveratrol to preserve cellular homeostasis under stress conditions. Resveratrol-induced HSP70 expression reduces the temperature threshold of the heat-shock response and preconditions the cells to cope with more severe or lethal stress levels. Resveratrol reduces glutathione disulphide (GSSG) formation, maintaining GSH in its reduced form to prevent ROS-induced cellular damage and, in addition, inhibits the H2O2-induced lipid peroxidation by reducing malondialdehyde (MDA) formation, while increasing SOD activity and inhibiting the elevated intracellular expression of ROS in Caco-2 cells. Resveratrol-induced HO-1 signaling is crucial in common expression of TJ proteins by inhibiting the PKC activity and P38 phosphorylation.

37Resveratrol alleviates the HS-induced intestinal damage by preserving villus height to crypt depth ratio in chickens. In vitro investigations using IPEC-J2 intestinal epithelial cells showed that resveratrol ameliorates intestinal epithelial integrity breakdown by increasing TEER values, reducing bacterial translocation, and decreasing the paracellular permeability. These effects were mainly associated by enhancement of claudin-4 TJ protein assembly. Moreover, in vitro and in vivo studies indicated that pre-treatment with resveratrol significantly hampered H2O2-induced damage to occludin and ZO-1 proteins in a concentration- and time-dependent manner in Caco-2 cells by upregulating HO-1 expression. In models of intestinal integrity disruption in rats, resveratrol treatment attenuated the gut hyperpermeability resulting from oxidative stress. Recent investigations by Mayangsari and Suzuki pointed out that resveratrol ameliorated DSS-induced ZO-1, ZO-2, occludin, JAM-A, claudin-2, claudin-3, claudin-4, and claudin-7 suppression.

38Oxy-resveratrol, an isomer of hydroxylated resveratrol, effectively decreases fluorescein isothiocyanate (FITC)-Dextran transport through the Caco-2 monolayer in a concentration-dependent manner. Occludin, ZO-1 and claudin-1 expression was significantly increased in oxy-resveratrol-treated Caco-2 cells compared to untreated cells, which might improve TJ integrity via PKC and MAPK-mediated pathways.

39Besides preserving the intestinal integrity, the induction of HSP by resveratrol induces immune-regulatory effects, since HSP are activators of anti-inflammatory regulatory T cells and HSP induction blocks the NF-κB activation by stabilizing IκB-α. Resveratrol treatment prevents the HS-induced transcription of NF-κB. In turn, resveratrol exerts an anti-inflammatory capacity by inhibiting COX-2 expression. COX-2 is a heat-responsive gene, upregulated as a HSF1 target gene under HS conditions. In addition, resveratrol reduces the transcription of pro-inflammatory cytokines, such as IL-6 and IL-1β, as well as COX-1 in Caco-2 cells, induced by LPS in combination with a cytokine cocktail. This underlines their safe use as preventative anti-inflammatory agent. As importantly, the immune-related cellular mechanisms modulated by resveratrol are associated with the stress-activated protein kinases/c-Jun N-terminal kinase (SAPK/JNK), ERK 1/2, p38 MAPK and spleen tyrosine kinase (Syk) signaling pathways.

40In conclusion, to restore the imbalance of the antioxidative system, quenching of excessive ROS by antioxidants, such as α-lipoic acid and resveratrol, is key. This process involves the improvement of the antioxidative enzyme system, activation of oxidative stress-modulating proteins, and inhibition of the inflammatory response. The effects of α-lipoic acid and resveratrol on intestinal integrity and immunomodulation are summarized in Table 2.

3.3. Polyunsaturated Fatty Acids (PUFA)

41Polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are members of the omega-3 fatty acid family. In the human diet, these fatty acids are mainly derived from fish and fish oil with high fat content. The importance of adequate EPA and DHA intake for the development of the fetal nervous system has been demonstrated. The effects of fatty acid intake on chronic diseases, including obesity, diabetes, cancer, arthritis, asthma, and cardiovascular diseases, are widely recognized. In addition, low doses of PUFA exert antioxidant activities and are cellular antioxidants that might positively modulate important physiological functions such as antioxidant capacity and enzymatic activities. The modulation mechanism involves quenching of intracellular ROS generation and direct inhibition of Nox4. Low dose EPA/DHA-fed rats displayed a higher activity of the antioxidant machinery, including an enhanced SOD and catalase (CAT) activity in addition to a reduction in total nitrate/nitrite content.

42EPA effectively attenuated the decrease in TEER and impairment of intestinal permeability in HRP flux induced by heat exposure. EPA significantly elevated the expression of occludin and ZO-1 in CaCo-2 cells. The distortion and redistribution of TJ proteins, and disruption of morphology were also effectively prevented by pre-treatment with EPA. A significant reduction in mucosal damage in the gut of rats was observed after an EPA/DHA supplemented diet, as reflected by the maintenance of total protein content. In Caco-2 cells, upon an acute inflammatory stimulus, DHA partially restored the occludin intensity in tight junction complexes, and preserved the ZO-1 localization and function by increasing TEER values and decreasing Lucifer Yellow (LY) flux in a concentration-dependent manner. DHA and EPA counteracted chronic stress-induced dysfunctions, such as the downregulation in ZO-1, occluding, and E-cadherin, and aberrant microbiota composition and their metabolites, mainly acetic acid, propionic acid, and butyric acid.

43DHA and EPA have anti-inflammatory activities and are used as “immunonutrients”. DHA and EPA decreased pro-inflammatory cytokines interferon (IFN)-γ, TNF-α, IL-1β, and IL-6 production in the intestine of mice exposed to chronic stress. This effect was mediated by up-regulating GPR120 and down-regulating TAK1/NF-κB p65 signaling. Zhao et al. reported that in colonic mucosa, DHA pre-treatment decreased immune cell infiltration, down-regulated IL-17, TNF-α, and INF-γ levels, and improved intestinal epithelial barrier function. In human colon cancer HT-29 cells, DHA and EPA inhibited ERK-1 and -2 phosphorylation and HIF-1α protein over-expression by reducing COX-2 expression and prostaglandin (PGE)2 levels. Furthermore, the other cellular mechanisms accounting for immunomodulatory effects also included down-regulation of inducible isoform of NOS (iNOS) and cyclic guanosine monophosphate (cGMP). In addition, EPA and DHA are able to increase cytokeratin 20 and mucin 2 gene and protein expression, which can enhance the intestinal immunological barrier by providing binding sites for antibacterial peptides.

44In summary, PUFA exert protective effects on the intestinal epithelial cell monolayer by protecting the barrier function and by anti-inflammatory activity. However, PUFA seem to have distinct effects at different concentration ranges in different disease models and in different cell lines. More in vivo studies are needed to determine the precise beneficial effects of PUFA on (HS-induced) intestinal disorders. The effects of DHA and EPA on intestinal integrity and immunomodulation are summarized in Table 3.

3.4. Amino Acids

45Nutrition deprivation experiments proved that amino acids are critical to the gut barrier and the gut microbiota. In the last decade, awareness of the nutritional relevance of some amino acids has been broadened from nutritional-only to therapeutically-important agents, due to their ability to modify cell signaling and to modulate gut-associated disorders. Functional amino acids, including arginine and glutamine enhance intestinal mucosal immunity, abolish the oxidative damage, trigger proliferation of enterocytes and enhance gut barrier function. Glutamine is not only the main fuel for enterocytes, but also plays a key role in mitogenesis, cytoprotection and barrier function. In addition, arginine through activation of focal adhesion kinase (FAK), mammalian target of rapamycin (mTOR), as well as nitric oxide (NO) cascades, actively participates in wound healing, and mucosal repair in intestinal epithelium.

3.4.1. Arginine

46Arginine supplementation attenuates the adverse effects of heat stroke in in vivo models. Therapeutic administration of arginine in mice and rats exposed to HS reduces the adverse effects of multi-organ failure, such as circulatory shock and cerebral ischemia, leading to improved survival. Arginine supplementation is also involved in the maintenance of intestinal homeostasis. Oral administration of arginine significantly enhances the intestinal recovery and accelerates the mucosal repair following ischemia-reperfusion injury in rats. In vitro, arginine suppresses apoptosis and cell death induced by LPS in porcine small intestinal cell line IPEC-1 cells. However, arginine in intestinal inflammation is a “double-edged sword”, because supra-physiological concentrations of arginine (>10 mM) may inhibit cell migration in intestinal wound edges and play a deleterious role in the pathogenesis of inflammation. Similarly, supra-physiological concentrations of arginine worsen the mucosal damage and gut barrier function after ischemia/reperfusion injury in rats. However, arginine supplementation in a physiological range plays an important role in the metabolic synthesis pathways, like the polyamine and NO production, which are involved in multiple cellular signaling pathways in enterocytes, including intestinal protein synthesis, blood flow, healing processes and intestinal immunity.

47HS blocks the physiological NO production, which, hence, will significantly increase the body heating rate, reduce the heat dissipation and increase the intestinal epithelial permeability. Therefore, basal NO level is a key factor in the enhancement of resilience to stress conditions. Physiological NO production enhances the tolerance to HS by reducing O2 costs under extensive exercise.

48Dietary arginine supplementation is important in attenuating the intestinal integrity disruption caused by exertional hyperthermia. Pre-treatment of Caco-2 cells with non-toxic arginine concentrations prevents the disruption of intestinal integrity. Arginine supplementation improves the intestinal integrity and preservation of TJs in experimental models of IBD and hypoxia. Arginine supplementation increases the mucus production as well as fluid secretion and inhibits intestinal hyper-motility in rats. Additionally, in vitro and in vivo studies showed that supplementation with arginine prevents bacterial translocation by reducing intestinal necrosis, increasing villus height, and attenuating gut mucosal injury.

49Different mechanisms may be involved in the arginine-induced tolerance of intestinal epithelial cells to HS, including:The NO synthesis pathway: Arginine, as a precursor of NO production, stimulates the enzyme NO synthase (NOS) isoforms to facilitate the synthesis and bioavailability of NO. The constitutive form of NOS (cNOS), which includes endothelial NOS (eNOS) and neuronal NOS (nNOS), generates relatively small amounts of NO, while iNOS produces a quantitatively larger amount of NO and is expressed in cells of the immune system as well as in intestinal epithelial cells.

50The NO synthesis pathway: Arginine, as a precursor of NO production, stimulates the enzyme NO synthase (NOS) isoforms to facilitate the synthesis and bioavailability of NO. The constitutive form of NOS (cNOS), which includes endothelial NOS (eNOS) and neuronal NOS (nNOS), generates relatively small amounts of NO, while iNOS produces a quantitatively larger amount of NO and is expressed in cells of the immune system as well as in intestinal epithelial cells.

51Although the precise mechanisms through which NO protects intestinal integrity is not fully understood, NO regulates the intestinal integrity by modulating intracellular signaling pathways related to protein tyrosine phosphorylation in epithelial cells. Protein tyrosine phosphorylation of TJ and AJ proteins, which can be induced by diverse oxidation-related stimuli including HS, is involved in barrier disruption under oxidative stress conditions. Additionally, NO signaling plays a key role in intestinal re-epithelialization and maintenance of intestinal integrity following mucosal injury. Mammalian target of rapamycin (mTOR) pathway: Maintaining the intestinal epithelial function by arginine can also be related to activation of the mTOR pathway. Arginine induces the downstream mTOR pathway by phosphorylation and activation of the protein synthesis regulator 70-kDa ribosomal protein S6 kinase (p70S6k). Activation of p70S6k by arginine increases protein synthesis, proliferation, and migration in disease conditions that induce intestinal epithelial injury. For instance, oral administration of arginine in a porcine model of enteritis augments intestinal protein synthesis and attenuates intestinal permeability via mTOR signaling and p70S6k activation.Arginase pathway: Metabolism of arginine via the arginase pathway results in the production of ornithine and polyamine, which promote intestinal epithelial repair and restitution processes. Polyamines are involved in the regulation of cell-cell interactions and E-cadherin expression, being critically important for the maintenance of intestinal epithelial integrity. Additionally, polyamines are important stress-responsive molecules, which facilitate the activation of HSF1 to induce HSP expression.

52Mammalian target of rapamycin (mTOR) pathway: Maintaining the intestinal epithelial function by arginine can also be related to activation of the mTOR pathway. Arginine induces the downstream mTOR pathway by phosphorylation and activation of the protein synthesis regulator 70-kDa ribosomal protein S6 kinase (p70S6k). Activation of p70S6k by arginine increases protein synthesis, proliferation, and migration in disease conditions that induce intestinal epithelial injury. For instance, oral administration of arginine in a porcine model of enteritis augments intestinal protein synthesis and attenuates intestinal permeability via mTOR signaling and p70S6k activation.

53Arginase pathway: Metabolism of arginine via the arginase pathway results in the production of ornithine and polyamine, which promote intestinal epithelial repair and restitution processes. Polyamines are involved in the regulation of cell-cell interactions and E-cadherin expression, being critically important for the maintenance of intestinal epithelial integrity. Additionally, polyamines are important stress-responsive molecules, which facilitate the activation of HSF1 to induce HSP expression.

54NO synthesis from arginine and the subsequent production of intestinal secretory immunoglobulin A (sIgA), modulate the expression of Th1/Th2 cytokines and prevent the exaggerated inflammatory responses followed by intestinal damage. One of the beneficial effects of arginine supplementation in preventing the intestinal inflammation in rats exposed to HS, may be mainly attributable to these immune-regulatory effects. Arginine supplementation reduces the expression of pro-inflammatory cytokines in the colon of mice with an experimental sodium dextran sulphate-induced colitis.

55It is likely that the main mechanism of action by which arginine modulates the inflammatory responses is the iNOS-induced NO production, which inhibits NF-κB, since inhibition of iNOS leads to the loss of all clinical benefits of arginine in the intestines.

3.4.2. Glutamine

56Nutritionally supplementary glutamine is traditionally classified as a non-essential amino acid. Glutamine is considered as an important precursor for the synthesis of nucleotides and proteins. Glutamine availability is effective in the maturation of rapidly proliferating intestinal epithelial cells in the gastrointestinal tract. Glutamine is a critically important fuel for the intestinal epithelial cells and is essential for preserving the intestinal mucosal barrier in humans and animals. In addition, circulating or luminal glutamine improves the gut function and mucosal integrity. Glutamine is important in regulating many key metabolic processes, such as protein synthesis, regulation of cellular redox status, and immune responses. One of the most described characteristics of glutamine is the enhancement of cell survival by inducing the expression of HSP.

57Animal research and clinical studies revealed that insufficient intake of glutamine is associated with the development of intestinal diseases and mucosal barrier breakdown, which can be reversed by glutamine supplementation. The effect of glutamine supplementation on gut micro-structures, such as amelioration of villus atrophy, has been previously described in different in vivo studies. Glutamine is essential to preserve the intestinal epithelial integrity, since the depletion of glutamine leads to the loss of TJ proteins and increased intestinal paracellular permeability as observed in epithelial cells. Incubation with L-glutamine significantly enhanced epithelial barrier function in primary porcine jejunal enterocytes by increasing occludin, claudin-4, JAM-A, ZO-1, ZO-2, ZO-3 protein expression. The glutamine-induced upregulation of HSP70 in the intestine prevents intestinal mucosal injury by improving the intestinal antioxidant capacity, such as elevating the superoxide dismutase, glutathione peroxidase, and total antioxidant capacity inhibiting lipid peroxidation. Interestingly, the glutamine-induced HSF-1 and HSP70 gene expressions are associated with a prevention of TJs disruption (ZO-1 and occludin), and thereby with protecting the intestinal epithelial cells from injuries caused by HS. Another mechanism by which glutamine exerts protective effects against intestinal oxidative stress is related to the up-regulation of HO-1. Inhibition of HO-1 abolishes the preventive effect of glutamine against intestinal damage caused by radiation in colon epithelial cells. Glutamine attenuates the disruption of intestinal epithelial tight junctions (ZO-1, claudin-1, occludin) and adherens junctions (E-cadherin and β-catenin) caused by acetaldehyde in Caco-2 cell monolayer. Glutamine is possibly involved in the regulation of apical junction complexes via tyrosine phosphorylation of the epidermal growth factor (EGF) receptor, since the protective effect of glutamine was eliminated by a specific inhibitor of EGF receptor tyrosine kinase. Glutamine can also regulate junctional proteins through the PI3-Kinase/Akt pathway. Differently, glutamine would hamper the methotrexate-induced disruption of tight junction proteins through JNK and ERK. In addition, AMPK could also be involved as a downstream target regulated by calcium/CaMKK2 signaling in response to glutamine supplementation.

58Food-supplemented glutamine upregulated the HSP70 levels in peripheral blood mononuclear cells (PBMC) of human exercise-induced HS. This can result in a reduction of pro-inflammatory cytokine secretion and thus an increased anti-inflammatory capacity and prevention of intestinal integrity disruption. Another human study has supported the role of glutamine in reducing pro-inflammatory cytokine secretion, such as IL-6 and IL-8, while increasing the anti-inflammatory cytokine IL-10 in the exercise-induced “leaky” intestines Moreover, feed supplementation with glutamine is associated with a reduction in LPS-induced intestinal inflammation in infant rats. A review summarized that glutamine can reduce inflammatory responses observed in different animal IBD models. Calves provided with alanyl-glutamine displayed an improvement in gain performance and health status concurrent with increases in blood CD2+ and CD4+ lymphocytes, the ratio of CD4+/CD8+, serum IgA and IgG, intestinal mucosal s-IgA, while decreasing the occurrence of diarrhea. Dietary glutamine supplementation decreased TNF-α levels, D-lactate, serum diamine oxidase (DAO) activity and soluble intercellular adhesion molecule (sICAM)-1 concentration, and increased IL-10 levels in the intestinal mucosa of broilers. The signaling pathway by which glutamine protects against inflammatory conditions is at least in part through stimulation of IκBα by HSP70 and associated suppression of NF-κB cascade.

59In conclusion, amino acids like arginine and glutamine play an important role in protein biosynthesis, but also exert physiological effects on signal transduction pathways that regulate immunity, preserve epithelial integrity, and regulate antioxidation and energy metabolism. Beneficial effects of arginine and glutamine in experimental models of intestinal disorders have been frequently reported. Despite promising data in experimental models, further studies are needed to evaluate amino acid supplementation in clinical practice. The effects of arginine and glutamine on intestinal integrity and immunomodulation are summarized in Table 4.

4. Concluding Remarks

60HS is considered as an important environmental stressor that is of increasing public health concern. Intervention strategies that can prevent, control, and reduce the pathologies (and even mortality) due to HS in humans and animals are therefore gaining increasing attention. Accumulating evidence suggests that the disruption of intestinal integrity followed by a generalized inflammatory response is a key event in human and animal pathologies under HS conditions. Subsequently, an increasing number of studies focus on the understanding of the molecular mechanisms involved in HS-induced inflammation and intestinal barrier disruption with the aim to introduce efficient strategies to preserve the physiologic performance of the gut (Figure 3). Future research needs to focus on the cellular and molecular pathways that act behind hyperthermia and hypoxia-induced pathologies. Currently, only a few classic cellular mechanisms, such as the heat shock and oxidative stress response, are clearly described. Furthermore, there are several gaps within the existing knowledge related to the effect of HS on junctional proteins.

61More than 40 tight junction proteins and more than 20 cadherin proteins have been identified, yet none of the junctional proteins studied have been found to be exclusively responsible for barrier homeostasis under hyperthermia or hypoxia conditions. It has been documented that HSP can bind to TJ proteins, such as ZO-1 and occludin, however, the causality between upregulation of specific HSP and restoration of TJ proteins still needs to be clarified. In addition, apart from a study by Bidmon-Fliegenschnee et al., and some “non-intestinal” studies suggesting a link between HSP/HSF and the catenin/cadherin family, our understanding about the interaction of HSP and AJ proteins is limited.

62As depicted in Figure 3, the described nutritional substances have a broad range of effects on HS-induced intestinal integrity disruption, inflammation, and oxidative stress. Nutritional substances, which have the potency to preserve not only cellular homeostasis by enhancing non-specific cellular defense systems, but also maintain intestinal integrity, are considered as promising feed/food supplements to protect animals and humans against the adverse effects of HS.

63Accumulating evidence indicates that provision of a combination of nutritional substances is more effective than treatment with a single dietary component. Synbiotics, a combination of probiotics and prebiotics, have been shown to exert synergistic effects in the intestinal tract. Microbiota-stabilizing compounds in combination with other nutritional substances can also enhance beneficial health effects and can possibly be used in a broader range of clinical conditions. For example, a prebiotic fiber diet combining with resveratrol and DHA was effective in lessening brain injury in rats. It will be a promising approach in the future to investigate the combination of different nutritional substances in (HS-associated) intestinal problems, offering innumerable possibilities to therapeutic practice.

References 258

1.
Furness J.B., Kunze W.A., Clerc N. Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: Neural, endocrine, and immune responses. Am. J. Physiol. 1999;277:G922-G928.
Not in our library10.1152/ajpgi.1999.277.5.g922
2.
Lambert G.P. Stress-induced gastrointestinal barrier dysfunction and its inflammatory effects. J. Anim. Sci. 2009;87:101-108.
Not in our library10.2527/jas.2008-1339
3.
Peterson L.W., Artis D. Intestinal epithelial cells: Regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 2014;14:141-153.
Not in our library10.1038/nri3608
4.
Bouchama A., Knochel J.P. Heat stroke. N. Engl. J. Med. 2002;346:1978-1988.
Not in our library10.1056/nejmra011089
5.
Leon L.R., Helwig B.G. Heat stroke: Role of the systemic inflammatory response. J. Appl. Physiol. 2010;109:1980-1988.
Not in our library10.1152/japplphysiol.00301.2010
6.
Epstein Y., Roberts W.O. The pathopysiology of heat stroke: An integrative view of the final common pathway. Scand. J. Med. Sci. Sports. 2011;21:742-748.
Not in our library10.1111/j.1600-0838.2011.01333.x
7.
Littmann A.E., Shields R.K. Whole body heat stress increases motor cortical excitability and skill acquisition in humans. Clin. Neurophysiol. 2016;127:1521-1529.
Not in our library10.1016/j.clinph.2015.11.001
8.
Fan H., Zhao Y., Zhu J.-H., Song F.-C., Ye J.-H., Wang Z.-Y., Le J.-W. Thrombocytopenia as a predictor of severe acute kidney injury in patients with heat stroke. Ren. Fail. 2015;37:877-881.
Not in our library10.3109/0886022x.2015.1022851
9.
Heneghan H.M., Nazirawan F., Dorcaratto D., Fiore B., Boylan J.F., Maguire D., Hoti E. Extreme heatstroke causing fulminant hepatic failure requiring liver transplantation: A case report. Transplant. Proc. 2014;46:2430-2432.
Not in our library10.1016/j.transproceed.2013.12.055
10.
Welc S.S., Clanton T.L., Dineen S.M., Leon L.R. Heat stroke activates a stress-induced cytokine response in skeletal muscle. J. Appl. Physiol. 2013;115:1126-1137.
Not in our library10.1152/japplphysiol.00636.2013
11.
Lambert G.P., Gisolfi C.V., Berg D.J., Moseley P.L., Oberley L.W., Kregel K.C. Selected contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. J. Appl. Physiol. 2002;92:1750-1761.
Not in our library10.1152/japplphysiol.00787.2001
12.
Yamoto M., Lee C., Chusilp S., Yazaki Y., Alganabi M., Li B., Pierro A. The role of autophagy in intestinal epithelial injury. Pediatr. Surg. Int. 2019;35:1389-1394.
Not in our library10.1007/s00383-019-04566-2
13.
Shah Y.M. The role of hypoxia in intestinal inflammation. Mol. Cell. Pediatr. 2016;3:1.
Not in our library10.1186/s40348-016-0030-1
14.
Vissenaekens H., Grootaert C., Rajkovic A., Van De Wiele T., Calatayud M. The response of five intestinal cell lines to anoxic conditions in vitro. Biol. Cell. 2019;111:232-244.
Not in our library10.1111/boc.201800076
15.
Belhadj Slimen I., Najar T., Ghram A., Abdrrabba M. Heat stress effects on livestock: Molecular, cellular and metabolic aspects, a review. J. Anim. Physiol. Anim. Nutr. 2016;100:401-412.
Not in our library10.1111/jpn.12379
16.
Settar P., Yalçin S., Türkmut L., Ozkan S., Cahanar A. Season by genotype interaction related to broiler growth rate and heat tolerance. Poult. Sci. 1999;78:1353-1358.
Not in our library10.1093/ps/78.10.1353
17.
Deeb N., Lamont S.J. Genetic architecture of growth and body composition in unique chicken populations. J. Hered. 2002;93:107-118.
Not in our library10.1093/jhered/93.2.107
18.
Tsiouris V., Georgopoulou I., Batzios C., Pappaioannou N., Ducatelle R., Fortomaris P. Heat stress as a predisposing factor for necrotic enteritis in broiler chicks. Avian Pathol. 2018;47:616-624.
Not in our library10.1080/03079457.2018.1524574
19.
Zhu L., Liao R., Wu N., Zhu G., Yang C. Heat stress mediates changes in fecal microbiome and functional pathways of laying hens. Appl. Microbiol. Biotechnol. 2019;103:461-472.
Not in our library10.1007/s00253-018-9465-8
20.
Akerfelt M., Morimoto R.I., Sistonen L. Heat shock factors: Integrators of cell stress, development and lifespan. Nat. Rev. Mol. Cell Biol. 2010;11:545-555.
Not in our library10.1038/nrm2938
21.
Joly A.-L., Wettstein G., Mignot G., Ghiringhelli F., Garrido C. Dual role of heat shock proteins as regulators of apoptosis and innate immunity. J. Innate Immun. 2010;2:238-247.
Not in our library10.1159/000296508
22.
Lee H.-J., Ock C.Y., Kim S.-J., Hahm K.-B. Heat shock protein: Hard worker or bad offender for gastric diseases. Int. J. Proteom. 2010;2010:259163.
Not in our library10.1155/2010/259163
23.
Cellular Stress Responses: Cell Survival and Cell Death · 2010
No notice
24.
Association between heat stress and oxidative stress in poultry; mitochondrial dysfunction and dietary interventions with phytochemicals · 2016
No notice
25.
Superoxide radical production in chicken skeletal muscle induced by acute heat stress. Poult. Sci. 2005;84:307-314.
Not in our library10.1093/ps/84.2.307
26.
Christen F., Desrosiers V., Dupont-Cyr B.A., Vandenberg G.W., Le François N.R., Tardif J.C., Dufresne F., Lamarre S.G., Blier P.U. Thermal tolerance and thermal sensitivity of heart mitochondria: Mitochondrial integrity and ROS production. Free Radic. Biol. Med. 2018;116:11-18.
Not in our library10.1016/j.freeradbiomed.2017.12.037
27.
King M.A., Clanton T.L., Laitano O. Hyperthermia, dehydration and osmotic stress: Unconventional sources of exercise-induced reactive oxygen species. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2015;310:105-114.
Not in our library10.1152/ajpregu.00395.2015
28.
de Roos B., Duthie G.G. Role of dietary pro-oxidants in the maintenance of health and resilience to oxidative stress. Mol. Nutr. Food Res. 2015;59:1229-1248.
Not in our library10.1002/mnfr.201400568
29.
Kovac S., Angelova P.R., Holmström K.M., Zhang Y., Dinkova-Kostova A.T., Abramov A.Y. Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochim. Biophys. Acta. 2015;1850:794-801.
Not in our library10.1016/j.bbagen.2014.11.021
30.
Ivan M., Kondo K., Yang H., Kim W., Valiando J., Ohh M., Salic A., Asara J.M., Lane W.S., Kaelin J. HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science. 2001;292:464-468.
Not in our library10.1126/science.1059817
31.
Guzy R.D., Mack M.M., Schumacker P.T. Mitochondrial complex III is required for hypoxia-induced ROS production and gene transcription in yeast. Antioxid. Redox Signal. 2007;9:1317-1328.
Not in our library10.1089/ars.2007.1708
32.
Chandel N.S., McClintock D.S., Feliciano C.E., Wood T.M., Melendez J.A., Rodriguez A.M., Schumacker P.T. Reactive oxygen species generated at mitochondrial Complex III stabilize hypoxia-inducible factor-1α during hypoxia: A mechanism of O2 sensing. J. Biol. Chem. 2000;275:25130-25138.
Not in our library10.1074/jbc.m001914200
33.
Dokladny K., Zuhl M.N., Moseley P.L. Intestinal epithelial barrier function and tight junction proteins with heat and exercise. J. Appl. Physiol. 2016;120:692-701.
Not in our library10.1152/japplphysiol.00536.2015
34.
Dokladny K., Ye D., Kennedy J.C., Moseley P.L., Ma T.Y. Cellular and molecular mechanisms of heat stress-induced up-regulation of occludin protein expression: Regulatory role of heat shock factor-1. Am. J. Pathol. 2008;172:659-670.
Not in our library10.2353/ajpath.2008.070522
35.
Varasteh S., Braber S., Kraneveld A.D., Garssen J., Fink-Gremmels J. l-Arginine supplementation prevents intestinal epithelial barrier breakdown under heat stress conditions by promoting nitric oxide synthesis. Nutr. Res. 2018;57:45-55.
Not in our library10.1016/j.nutres.2018.05.007
36.
Zuhl M., Schneider S., Lanphere K., Conn C., Dokladny K., Moseley P. Exercise regulation of intestinal tight junction proteins. Br. J. Sports Med. 2014;48:980-986.
Not in our library10.1136/bjsports-2012-091585
37.
Yang P.-C., He S.-H., Zheng P.-Y. Investigation into the signal transduction pathway via which heat stress impairs intestinal epithelial barrier function. J. Gastroenterol. Hepatol. 2007;22:1823-1831.
Not in our library10.1111/j.1440-1746.2006.04710.x
38.
Tsapara A., Matter K., Balda M.S. The heat-shock protein Apg-2 binds to the tight junction protein ZO-1 and regulates transcriptional activity of ZONAB. Mol. Biol. Cell. 2006;17:1322-1330.
Not in our library10.1091/mbc.e05-06-0507
39.
Bidmon-Fliegenschnee B., Lederhuber H.C., Csaicsich D., Pichler J., Herzog R., Memaran-Dadgar N., Huber W.-D., Aufricht C., Kratochwill K. Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells. Pediatr. Res. 2015;78:358-364.
Not in our library10.1038/pr.2015.112
40.
Jin W., Wang H., Ji Y., Hu Q., Yan W., Chen G., Yin H. Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2-deficient mice after traumatic brain injury. Cytokine. 2008;44:135-140.
Not in our library10.1016/j.cyto.2008.07.005
41.
Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway · 2019
No notice
42.
Liu Y., Bao Z., Xu X., Chao H., Lin C., Li Z., Liu Y., Wang X., You Y., Liu N., et al. Extracellular signal-regulated kinase/nuclear factor-erythroid2-like2/heme oxygenase-1 pathway-mediated mitophagy alleviates traumatic brain injury-induced intestinal mucosa damage and epithelial barrier dysfunction. J. Neurotrauma. 2017;34:2119-2131.
Not in our library10.1089/neu.2016.4764
43.
Chen H., Hu Y., Fang Y., Djukic Z., Yamamoto M., Shaheen N.J., Orlando R.C., Chen X. Nrf2 deficiency impairs the barrier function of mouse oesophageal epithelium. Gut. 2014;63:711-719.
Not in our library10.1136/gutjnl-2012-303731
44.
Samborski P., Grzymisławski M. The role of HSP70 heat shock proteins in the pathogenesis and treatment of inflammatory bowel diseases. Adv. Clin. Exp. Med. 2015;24:525-530.
Not in our library10.17219/acem/44144
45.
Sziksz E., Veres G., Vannay A., Prókai A., Gál K., Onody A., Korponay-Szabó I.R., Reusz G., Szabó A., Tulassay T., et al. Increased heat shock protein 72 expression in celiac disease. J. Pediatr. Gastroenterol. Nutr. 2010;51:573-578.
Not in our library10.1097/mpg.0b013e3181ea0092
46.
Pritts T.A., Wang Q., Sun X., Moon M.R., Fischer D.R., Fischer J.E., Wong H.R., Hasselgren P.O. Induction of the stress response in vivo decreases nuclear factor-kappa B activity in jejunal mucosa of endotoxemic mice. Arch. Surg. 2000;135:860-866.
Not in our library10.1001/archsurg.135.7.860
47.
Shi Y., Tu Z., Tang D., Zhang H., Liu M., Wang K., Calderwood S.K., Xiao X. The inhibition of LPS-induced production of inflammatory cytokines by HSP70 involves inactivation of the NF-kappaB pathway but not the MAPK pathways. Shock. 2006;26:277-284.
Not in our library10.1097/01.shk.0000223134.17877.ad
48.
van Eden W. Diet and the anti-inflammatory effect of heat shock proteins. Endocr. Metab. Immune Disord. Drug Targets. 2015;15:31-36.
Not in our library10.2174/1871530314666140922145333
49.
van Puijvelde G.H.M., van Es T., van Wanrooij E.J.A., Habets K.L.L., de Vos P., van der Zee R., van Eden W., van Berkel T.J.C., Kuiper J. Induction of oral tolerance to HSP60 or an HSP60-peptide activates T cell regulation and reduces atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2007;27:2677-2683.
Not in our library10.1161/atvbaha.107.151274
50.
Maron R., Sukhova G., Faria A.-M., Hoffmann E., Mach F., Libby P., Weiner H.L. Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aortic arch of low-density lipoprotein receptor-deficient mice. Circulation. 2002;106:1708-1715.
Not in our library10.1161/01.cir.0000029750.99462.30
51.
Hauet-Broere F., Wieten L., Guichelaar T., Berlo S., van der Zee R., Van Eden W. Heat shock proteins induce T cell regulation of chronic inflammation. Ann. Rheum. Dis. 2006;65:iii65-iii68.
Not in our library10.1136/ard.2006.058495
52.
Borges T.J., Wieten L., Van Herwijnen M.J.C., Broere F., Van derZee R., Bonorino C., Van Eden W. The anti-inflammatory mechanisms of Hsp70. Front. Immunol. 2012;3:95.
Not in our library10.3389/fimmu.2012.00095
53.
Spierings J., van Eden W. Heat shock proteins and their immunomodulatory role in inflammatory arthritis. Rheumatology. 2017;56:198-208.
Not in our library10.1093/rheumatology/kew266
54.
Morgan M.J., Liu Z. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 2011;21:103-115.
Not in our library10.1038/cr.2010.178
55.
Dayalan Naidu S., Kostov R.V., Dinkova-Kostova A.T. Transcription factors Hsf1 and Nrf2 engage in crosstalk for cytoprotection. Trends Pharmacol. Sci. 2015;36:6-14.
Not in our library10.1016/j.tips.2014.10.011
56.
Hensen S.M.M., Heldens L., Van Genesen S.T., Pruijn G.J.M., Lubsen N.H. A delayed antioxidant response in heat-stressed cells expressing a non-DNA binding HSF1 mutant. Cell Stress Chaperones. 2013;18:455-473.
Not in our library10.1007/s12192-012-0400-0
57.
Zagorski J.W., Turley A.E., Freeborn R.A., VanDenBerg K.R., Dover H.E., Kardell B.R., Liby K.T., Rockwell C.E. Differential effects of the Nrf2 activators tBHQ and CDDO-Im on the early events of T cell activation. Biochem. Pharmacol. 2018;147:67-76.
Not in our library10.1016/j.bcp.2017.11.005
58.
Turley A.E., Zagorski J.W., Rockwell C.E. The Nrf2 activator tBHQ inhibits T cell activation of primary human CD4 T cells. Cytokine. 2015;71:289-295.
Not in our library10.1016/j.cyto.2014.11.006
59.
Awuh J.A., Haug M., Mildenberger J., Marstad A., Do C.P.N., Louet C., Stenvik J., Steigedal M., Damås J.K., Halaas Ø., et al. Keap1 regulates inflammatory signaling in Mycobacterium avium -infected human macrophages. Proc. Natl. Acad. Sci. USA. 2015;112:E4272-E4280.
Not in our library10.1073/pnas.1423449112
60.
Mach N., Fuster-Botella D. Endurance exercise and gut microbiota: A review. J. Sport Health Sci. 2017;6:179-197.
Not in our library10.1016/j.jshs.2016.05.001
61.
Suzuki K., Harasawa R., Yoshitake Y., Mitsuoka T. Effects of crowding and heat stress on intestinal flora, body weight gain, and feed efficiency of growing rats and chicks. Jpn. J. Vet. Sci. 1983;45:331-338.
Not in our library10.1292/jvms1939.45.331
62.
Johnson-Henry K.C., Abrahamsson T.R., Wu R.Y., Sherman P.M. Probiotics, Prebiotics, and synbiotics for the prevention of necrotizing enterocolitis. Adv. Nutr. 2016;7:928-937.
Not in our library10.3945/an.116.012237
63.
Farag M.R., Alagawany M. Physiological alterations of poultry to the high environmental temperature. J. Therm. Biol. 2018;76:101-106.
Not in our library10.1016/j.jtherbio.2018.07.012
64.
Ribet D., Cossart P. How bacterial pathogens colonize their hosts and invade deeper tissues. Microbes Infect. 2015;17:173-183.
Not in our library10.1016/j.micinf.2015.01.004
65.
Ducray H.A.G., Globa L., Pustovyy O., Vodyanoy V., Sorokulova I. Prebiotics and probiotics maintain the intestinal barrier function. FASEB J. 2019;33:589.7.
Not in our library
66.
Shokryazdan P., Faseleh Jahromi M., Navidshad B., Liang J.B. Effects of prebiotics on immune system and cytokine expression. Med. Microbiol. Immunol. 2017;206:1-9.
Not in our library10.1007/s00430-016-0481-y
67.
Quigley E.M.M. Prebiotics and probiotics in digestive health. Clin. Gastroenterol. Hepatol. 2019;17:333-344.
Not in our library10.1016/j.cgh.2018.09.028
68.
Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond · 2019
No notice
69.
Reid G. Probiotics: Definition, scope and mechanisms of action. Best Pract. Res. Clin. Gastroenterol. 2016;30:17-25.
Not in our library10.1016/j.bpg.2015.12.001
70.
Shing C.M., Peake J.M., Lim C.L., Briskey D., Walsh N.P., Fortes M.B., Ahuja K.D.K., Vitetta L. Effects of probiotics supplementation on gastrointestinal permeability, inflammation and exercise performance in the heat. Eur. J. Appl. Physiol. 2014;114:93-103.
Not in our library10.1007/s00421-013-2748-y
71.
Shukla G., Sidhu R.K. Lactobacillus casei as a probiotic in malnourished Giardia lamblia -infected mice: A biochemical and histopathological study. Can. J. Microbiol. 2011;57:127-135.
Not in our library10.1139/w10-110
72.
Rowland I.R., Capurso L., Collins K., Cummings J., Delzenne N., Goulet O., Guarner F., Marteau P., Meier R. Current level of consensus on probiotic science-Report of an expert meeting—London, 23 November 2009. Gut Microbes. 2010;1:436-439.
Not in our library10.4161/gmic.1.6.13610
73.
Rao R.K., Samak G. Protection and restitution of gut barrier by probiotics: Nutritional and clinical implications. Curr. Nutr. Food Sci. 2013;9:99-107.
Not in our library10.2174/1573401311309020004
74.
Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial · 2012
No notice
75.
Barnett A., Roy N., Cookson A., McNabb W. Metabolism of caprine milk carbohydrates by probiotic bacteria and caco-2:HT29–MTX epithelial co-cultures and their impact on intestinal barrier integrity. Nutrients. 2018;10:949.
Not in our library10.3390/nu10070949
76.
Ashraf S., Zaneb H., Yousaf M.S., Ijaz A., Sohail M.U., Muti S., Usman M.M., Ijaz S., Rehman H. Effect of dietary supplementation of prebiotics and probiotics on intestinal microarchitecture in broilers reared under cyclic heat stress. J. Anim. Physiol. Anim. Nutr. 2013;97:68-73.
Not in our library10.1111/jpn.12041
77.
Song J., Xiao K., Ke Y.L., Jiao L.F., Hu C.H., Diao Q.Y., Shi B., Zou X.T. Effect of a probiotic mixture on intestinal microflora, morphology, and barrier integrity of broilers subjected to heat stress. Poulty Sci. 2014;93:581-588.
Not in our library10.3382/ps.2013-03455
78.
Lee N.K., Kim W.S., Paik H.D. Bacillus strains as human probiotics: Characterization, safety, microbiome, and probiotic carrier. Food Sci. Biotechnol. 2019;28:1297-1305.
Not in our library10.1007/s10068-019-00691-9
79.
Rajput I.R., Li L., Xin X., Wu B., Juan Z., Cui Z., Yu D., Li W. Effect of Saccharomyces boulardii and Bacillus subtilis B10 on intestinal ultrastructure modulation and mucosal immunity development mechanism in broiler chickens. Poult. Sci. 2013;92:956-965.
Not in our library10.3382/ps.2012-02845
80.
Moore T., Globa L., Pustovyy O., Vodyanoy V., Sorokulova I. Oral administration of Bacillus subtilis strain BSB3 can prevent heat stress-related adverse effects in rats. J. Appl. Microbiol. 2014;117:1463-1471.
Not in our library10.1111/jam.12606
81.
Zyrek A.A., Cichon C., Helms S., Enders C., Sonnenborn U., Schmidt M.A. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair. Cell. Microbiol. 2007;9:804-816.
Not in our library10.1111/j.1462-5822.2006.00836.x
82.
Hummel S., Veltman K., Cichon C., Sonnenborn U., Schmidt M.A. Differential targeting of the E-Cadherin/β-Catenin complex by gram-positive probiotic lactobacilli improves epithelial barrier function. Appl. Environ. Microbiol. 2012;78:1140-1147.
Not in our library10.1128/aem.06983-11
83.
Probiotic-Derived Polyphosphate Enhances the Epithelial Barrier Function and Maintains Intestinal Homeostasis through Integrin–p38 MAPK Pathway · 2011
No notice
84.
Trivedi K., Barrett K.E., Silvia C.R.-L. Probiotic inhibition of the entry of enteroinvasive E. coli into, human intestinal epithelial cells involves both Rho-dependent and -independent pathways. Gastroenterology. 2003;124:A106.
Not in our library10.1016/s0016-5085(03)80524-3
85.
Deng W., Dong X.F., Tong J.M., Zhang Q. The probiotic Bacillus licheniformis ameliorates heat stress-induced impairment of egg production, gut morphology, and intestinal mucosal immunity in laying hens. Poult. Sci. 2012;91:575-582.
Not in our library10.3382/ps.2010-01293
86.
Giorgetti G., Brandimarte G., Fabiocchi F., Ricci S., Flamini P., Sandri G., Trotta M.C., Elisei W., Penna A., Lecca P.G., et al. Interactions between innate immunity, microbiota, and probiotics. J. Immunol. Res. 2015;2015:501361.
Not in our library10.1155/2015/501361
87.
Viladomiu M., Hontecillas R., Yuan L., Lu P., Bassaganya-Riera J. Nutritional protective mechanisms against gut inflammation. J. Nutr. Biochem. 2013;24:929-939.
Not in our library10.1016/j.jnutbio.2013.01.006
88.
Lysate of Probiotic Lactobacillus casei DN-114 001 Ameliorates Colitis by Strengthening the Gut Barrier Function and Changing the Gut Microenvironment · 2011
No notice
89.
Probiotic Bifidobacterium breve Induces IL-10-Producing Tr1 Cells in the Colon · 2012
No notice
90.
Probiotics, Prebiotics and Immunomodulation of Gut Mucosal Defences: Homeostasis and Immunopathology · 2013
No notice
91.
Yahfoufi N., Mallet J., Graham E., Matar C. Role of probiotics and prebiotics in immunomodulation. Curr. Opin. Food Sci. 2018;20:82-91.
Not in our library10.1016/j.cofs.2018.04.006
92.
Remus D.M., van Kranenburg R., van Swam I.I., Taverne N., Bongers R.S., Wels M., Wells J.M., Bron P.A., Kleerebezem M., Van Kranenburg R., et al. Impact of 4 Lactobacillus plantarum capsular polysaccharide clusters on surface glycan composition and host cell signaling. Microb. Cell Fact. 2012;11:149.
Not in our library10.1186/1475-2859-11-149
93.
van Baarlen P., Wells J.M., Kleerebezem M. Regulation of intestinal homeostasis and immunity with probiotic lactobacilli. Trends Immunol. 2013;34:208-215.
Not in our library10.1016/j.it.2013.01.005
94.
Valcheva R., Dieleman L.A. Prebiotics: Definition and protective mechanisms. Best Pract. Res. Clin. Gastroenterol. 2016;30:27-37.
Not in our library10.1016/j.bpg.2016.02.008
95.
Wang C., Zhang M., Guo H., Yan J., Chen L., Teng W., Ren F., Li Y., Wang X., Luo J., et al. Human milk oligosaccharides activate epidermal growth factor receptor and protect against hypoxia-induced injuries in the mouse intestinal epithelium and Caco2 cells. J. Nutr. 2020.
Not in our library10.1093/jn/nxz297
96.
Holscher H.D., Faust K.L., Czerkies L.A., Litov R., Ziegler E.E., Lessin H., Hatch T., Sun S., Tappenden K.A. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. J. Parenter. Enter. Nutr. 2012;36:95S-105S.
Not in our library10.1177/0148607111430087
97.
Roberfroid M., Gibson G.R., Hoyles L., McCartney A.L., Rastall R., Rowland I., Wolvers D., Watzl B., Szajewska H., Stahl B., et al. Prebiotic effects: Metabolic and health benefits. Br. J. Nutr. 2010;104:S1-S63.
Not in our library10.1017/s0007114510003363
98.
Jeurink P.V., van Esch B.C., Rijnierse A., Garssen J., Knippels L.M. Mechanisms underlying immune effects of dietary oligosaccharides. Am. J. Clin. Nutr. 2013;98:572-577.
Not in our library10.3945/ajcn.112.038596
99.
Bhatia S., Prabhu P.N., Benefiel A.C., Miller M.J., Chow J., Davis S.R., Gaskins H.R. Galacto-oligosaccharides may directly enhance intestinal barrier function through the modulation of goblet cells. Mol. Nutr. Food Res. 2015;59:566-573.
Not in our library10.1002/mnfr.201400639
100.
Yang J., Martínez I., Walter J., Keshavarzian A., Rose D.J. Invitro characterization of the impact of selected dietary fibers on fecal microbiota composition and short chain fatty acid production. Anaerobe. 2013;23:74-81.
Not in our library10.1016/j.anaerobe.2013.06.012
101.
Hamer H.M., Jonkers D.M.A.E., Bast A., Vanhoutvin S.A.L.W., Fischer M.A.J.G., Kodde A., Troost F.J., Venema K., Brummer R.J.M. Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. Clin. Nutr. 2009;28:88-93.
Not in our library10.1016/j.clnu.2008.11.002
102.
Wong J.M.W., de Souza R., Kendall C.W.C., Emam A., Jenkins D.J.A. Colonic health: Fermentation and short chain fatty acids. J. Clin. Gastroenterol. 2006;40:235-243.
Not in our library10.1097/00004836-200603000-00015
103.
Slimen I.B., Najar T., Ghram A., Dabbebi H., Ben Mrad M., Abdrabbah M. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review. Int. J. Hyperth. 2014;30:513-523.
Not in our library10.3109/02656736.2014.971446
104.
Brown A.J., Goldsworthy S.M., Barnes A.A., Eilert M.M., Tcheang L., Daniels D., Muir A.I., Wigglesworth M.J., Kinghorn I., Fraser N.J., et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 2003;278:11312-11319.
Not in our library10.1074/jbc.m211609200
105.
Levy M., Blacher E., Elinav E. Microbiome, metabolites and host immunity. Curr. Opin. Microbiol. 2017;35:8-15.
Not in our library10.1016/j.mib.2016.10.003
106.
Song J., Jiao L.F., Xiao K., Luan Z.S., Hu C.H., Shi B., Zhan X.A. Cello-oligosaccharide ameliorates heat stress-induced impairment of intestinal microflora, morphology and barrier integrity in broilers. Anim. Feed Sci. Technol. 2013;185:175-181.
Not in our library10.1016/j.anifeedsci.2013.08.001
107.
Sohail M.U., Hume M.E., Byrd J.A., Nisbet D.J., Ijaz A., Sohail A., Shabbir M.Z., Rehman H. Effect of supplementation of prebiotic mannan-oligosaccharides and probiotic mixture on growth performance of broilers subjected to chronic heat stress. Poult. Sci. 2012;91:2235-2240.
Not in our library10.3382/ps.2012-02182
108.
Baurhoo B., Phillip L., Ruiz-Feria C.A. Effects of purified lignin and mannan oligosaccharides on intestinal integrity and microbial populations in the ceca and litter of broiler chickens. Poult. Sci. 2007;86:1070-1078.
Not in our library10.1093/ps/86.6.1070
109.
Chichlowski M., De Lartigue G., German J.B., Raybould H.E., Mills D.A. Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function. J. Pediatr. Gastroenterol. Nutr. 2012;55:321-327.
Not in our library10.1097/mpg.0b013e31824fb899
110.
Pan X., Wu T., Zhang L., Cai L., Song Z. Influence of oligosaccharides on the growth and tolerance capacity of lactobacilli to simulated stress environment. Lett. Appl. Microbiol. 2009;48:362-367.
Not in our library10.1111/j.1472-765x.2008.02539.x
111.
Yousef M., Pichyangkura R., Soodvilai S., Chatsudthipong V., Muanprasat C. Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: Therapeutic efficacy and possible mechanisms of action. Pharmacol. Res. 2012;66:66-79.
Not in our library10.1016/j.phrs.2012.03.013
112.
Differences in Susceptibility to Heat Stress along the Chicken Intestine and the Protective Effects of Galacto-Oligosaccharides · 2015
No notice
113.
Zhong Y., Cai D., Cai W., Geng S., Chen L., Han T. Protective effect of galactooligosaccharide-supplemented enteral nutrition on intestinal barrier function in rats with severe acute pancreatitis. Clin. Nutr. 2009;28:575-580.
Not in our library10.1016/j.clnu.2009.04.026
114.
Cai Y., Folkerts J., Folkerts G., Maurer M., Braber S. Microbiota-dependent and -independent effects of dietary fiber on human health. Br. J. Pharmacol. 2019.
Not in our library10.1111/bph.14871
115.
Wu R.Y., Abdullah M., Määttänen P., Pilar A.V.C., Scruten E., Johnson-Henry K.C., Napper S., O’Brien C., Jones N.L., Sherman P.M. Protein kinase C δ signaling is required for dietary prebiotic-induced strengthening of intestinal epithelial barrier function. Sci. Rep. 2017;7:40820.
Not in our library10.1038/srep40820
116.
Varasteh S., Braber S., Garssen J., Fink-Gremmels J. Galacto-oligosaccharides exert a protective effect against heat stress in a Caco-2 cell model. J. Funct. Foods. 2015;16:265-277.
Not in our library10.1016/j.jff.2015.04.045
117.
Akbari P., Braber S., Alizadeh A., Verheijden K.A., Schoterman M.H., Kraneveld A.D., Garssen J., Fink-Gremmels J. Galacto-oligosaccharides protect the intestinal barrier by maintaining the tight junction network and modulating the inflammatory responses after a challenge with the mycotoxin deoxynivalenol in human Caco-2 cell monolayers and B6C3F1 mice. J. Nutr. 2015;145:1604-1613.
Not in our library10.3945/jn.114.209486
118.
Akbari P., Fink-Gremmels J., Willems R.H.A.M., Difilippo E., Schols H.A., Schoterman M.H.C., Garssen J., Braber S. Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: Insight into the role of structure and size. Eur. J. Nutr. 2017;56:1919-1930.
Not in our library10.1007/s00394-016-1234-9
119.
Muanprasat C., Wongkrasant P., Satitsri S., Moonwiriyakit A., Pongkorpsakol P., Mattaveewong T., Pichyangkura R., Chatsudthipong V. Activation of AMPK by chitosan oligosaccharide in intestinal epithelial cells: Mechanism of action and potential applications in intestinal disorders. Biochem. Pharmacol. 2015;96:225-236.
Not in our library10.1016/j.bcp.2015.05.016
120.
Gribar S.C., Richardson W.M., Sodhi C.P., Hackam D.J. No longer an innocent bystander: Epithelial toll-like receptor signaling in the development of mucosal inflammation. Mol. Med. 2008;14:645-659.
Not in our library10.2119/2008-00035.gribar
121.
Peterson C.Y., Costantini T.W., Loomis W.H., Putnam J.G., Wolf P., Bansal V., Eliceiri B.P., Baird A., Coimbra R. Toll-like receptor-4 mediates intestinal barrier breakdown after thermal injury. Surg. Infect. (Larchmt). 2010;11:137-144.
Not in our library10.1089/sur.2009.053
122.
Antoni L., Nuding S., Wehkamp J., Stange E.F. Intestinal barrier in inflammatory bowel disease. World J. Gastroenterol. 2014;20:1165-1179.
Not in our library10.3748/wjg.v20.i5.1165
123.
Wang C., Zhang M., Guo H., Yan J., Liu F., Chen J., Li Y., Ren F. Human milk oligosaccharides protect against necrotizing enterocolitis by inhibiting intestinal damage via increasing the proliferation of crypt cells. Mol. Nutr. Food Res. 2019;63:e1900262.
Not in our library10.1002/mnfr.201900262
124.
Mollen K.P., Anand R.J., Tsung A., Prince J.M., Levy R.M., Billiar T.R. Emerging paradigm: Toll-like receptor 4-sentinel for the detection of tissue damage. Shock. 2006;26:430-437.
Not in our library10.1097/01.shk.0000228797.41044.08
125.
Breslin J.W., Wu M.H., Guo M., Reynoso R., Yuan S.Y. Toll-like receptor 4 contributes to microvascular inflammation and barrier dysfunction in thermal injury. Shock. 2008;29:349-355.
Not in our library10.1097/shk.0b013e3181454975
126.
Frye R., Frye R., Slattery J., MacFabe D. The significance of the enteric microbiome on the development of childhood disease: A review of prebiotic and probiotic therapies in disorders of childhood. Clin. Med. Insights Pediatr. 2016.
Not in our library10.4137/cmped.s38338
127.
Ishikawa H., Matsumoto S., Ohashi Y., Imaoka A., Setoyama H., Umesaki Y., Tanaka R., Otani T. Beneficial effects of probiotic Bifidobacterium and galacto-oligosaccharide in patients with ulcerative colitis: A randomized controlled study. Digestion. 2011;84:128-133.
Not in our library10.1159/000322977
128.
Videla S., Vilaseca J., Antolin M., Garcia-Lafuente A., Guarner F., Crespo E., Casalots J., Salas A., Malagelada J.R. Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat. Am. J. Gastroenterol. 2001;96:1486-1493.
Not in our library10.1111/j.1572-0241.2001.03802.x
129.
de Kivit S., Saeland E., Kraneveld A.D., van de Kant H.J.G., Schouten B., van Esch B.C.A.M., Knol J., Sprikkelman A.B., van der Aa L.B., Knippels L.M.J., et al. Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans. Allergy. 2012;67:343-352.
Not in our library10.1111/j.1398-9995.2011.02771.x
130.
Jantscher-Krenn E., Zherebtsov M., Nissan C., Goth K., Guner Y.S., Naidu N., Choudhury B., Grishin A.V., Ford H.R., Bode L. The human milk oligosaccharide disialyllacto-N-tetraose prevents necrotising enterocolitis in neonatal rats. Gut. 2012;61:1417-1425.
Not in our library10.1136/gutjnl-2011-301404
131.
Damaskos D., Kolios G. Probiotics and prebiotics in inflammatory bowel disease: Microflora “on the scope”. Br. J. Clin. Pharmacol. 2008;65:453-467.
Not in our library10.1111/j.1365-2125.2008.03096.x
132.
Nam K.-S., Kim M.-K., Shon Y.-H. Inhibition of proinflammatory cytokine-induced invasiveness of HT-29 cells by chitosan oligosaccharide. J. Microbiol. Biotechnol. 2007;17:2042-2045.
Not in our library
133.
Nam K.-S., Kim M.-K., Shon Y.-H. Chemopreventive effect of chitosan oligosaccharide against colon carcinogenesis. J. Microbiol. Biotechnol. 2007;17:1546-1549.
Not in our library
134.
Verheijden K.A.T., Akbari P., Willemsen L.E.M., Kraneveld A.D., Folkerts G., Garssen J., Fink-Gremmels J., Braber S. Inflammation-induced expression of the alarmin interleukin 33 can be suppressed by galacto-oligosaccharides. Int. Arch. Allergy Immunol. 2015;167:127-136.
Not in our library10.1159/000437327
135.
Faseleh Jahromi M., Wesam Altaher Y., Shokryazdan P., Ebrahimi R., Ebrahimi M., Idrus Z., Tufarelli V., Liang J.B. Dietary supplementation of a mixture of Lactobacillus strains enhances performance of broiler chickens raised under heat stress conditions. Int. J. Biometeorol. 2016;60:1099-1110.
Not in our library10.1007/s00484-015-1103-x
136.
Wu R.Y., Li B., Koike Y., Määttänen P., Miyake H., Cadete M., Johnson-Henry K.C., Botts S.R., Lee C., Abrahamsson T.R., et al. Human milk oligosaccharides increase mucin expression in experimental necrotizing enterocolitis. Mol. Nutr. Food Res. 2019;63:1800658.
Not in our library10.1002/mnfr.201800658
137.
Cherbut C., Michel C., Lecannu G. The prebiotic characteristics of fructooligosaccharides are necessary for reduction of TNBS-induced colitis in rats. J. Nutr. 2003;133:21-27.
Not in our library10.1093/jn/133.1.21
138.
Wen Z., Liu W., Li X., Chen W., Liu Z., Wen J., Liu Z. A protective role of the NRF2-Keap1 pathway in maintaining intestinal barrier function. Oxid. Med. Cell. Longev. 2019;2019:1759149.
Not in our library10.1155/2019/1759149
139.
Role of ROS and RNS Sources in Physiological and Pathological Conditions · 2016
No notice
140.
Blanco A., Blanco G., Blanco A., Blanco G. Chapter 10—Antioxidants. Medical Biochemistry. 2017;205-214.
Not in our library
141.
Li J., Liu Y., Duan P., Yu R., Gu Z., Li L., Liu Z., Su L. NF-κB regulates HSF1 and c-Jun activation in heat stress-induced intestinal epithelial cell apoptosis. Mol. Med. Rep. 2018;17:3388-3396.
Not in our library10.3892/mmr.2017.8199
142.
Yu J., Liu F., Yin P., Zhao H., Luan W., Hou X., Zhong Y., Jia D., Zan J., Ma W., et al. Involvement of oxidative stress and mitogen-activated protein kinase signaling pathways in heat stress-induced injury in the rat small intestine. Stress. 2013;16:99-113.
Not in our library10.3109/10253890.2012.680526
143.
Shila S., Subathra M., Devi M.A., Panneerselvam C. Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: Reversal by DL-alpha-lipoic acid. Arch. Toxicol. 2005;79:140-146.
Not in our library10.1007/s00204-004-0614-8
144.
Rochette L., Ghibu S., Richard C., Zeller M., Cottin Y., Vergely C. Direct and indirect antioxidant properties of α-lipoic acid and therapeutic potential. Mol. Nutr. Food Res. 2013;57:114-125.
Not in our library10.1002/mnfr.201200608
145.
Trivedi P.P., Jena G.B. Role of α-lipoic acid in dextran sulfate sodium-induced ulcerative colitis in mice: Studies on inflammation, oxidative stress, DNA damage and fibrosis. Food Chem. Toxicol. 2013;59:339-355.
Not in our library10.1016/j.fct.2013.06.019
146.
Fan P., Tan Y., Jin K., Lin C., Xia S., Han B., Zhang F., Wu L., Ma X. Supplemental lipoic acid relieves post-weaning diarrhoea by decreasing intestinal permeability in rats. J. Anim. Physiol. Anim. Nutr. 2017;101:136-146.
Not in our library10.1111/jpn.12427
147.
Varasteh S., Fink-Gremmels J., Garssen J., Braber S., Nl S.B. α-Lipoic acid prevents the intestinal epithelial monolayer damage under heat stress conditions: Model experiments in Caco-2 cells. Eur. J. Nutr. 2018;57:1577-1589.
Not in our library10.1007/s00394-017-1442-y
148.
Ma X., He P., Sun P., Han P. Lipoic acid: An immunomodulator that attenuates glycinin-induced anaphylactic reactions in a rat model. J. Agric. Food Chem. 2010;58:5086-5092.
Not in our library10.1021/jf904403u
149.
Rao R.K., Basuroy S., Rao V.U., Karnaky K.J., Gupta A. Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-β-catenin complexes from the cytoskeleton by oxidative stress. Biochem. J. 2002;368:471-481.
Not in our library10.1042/bj20011804
150.
Koriyama Y., Nakayama Y., Matsugo S., Kato S. Protective effect of lipoic acid against oxidative stress is mediated by Keap1/Nrf2-dependent heme oxygenase-1 induction in the RGC-5 cell line. Brain Res. 2013;1499:145-157.
Not in our library10.1016/j.brainres.2012.12.041
151.
Durante W. Protective role of heme oxygenase-1 against inflammation in atherosclerosis. Front. Biosci. 2011;16:2372-2388.
Not in our library10.2741/3860
152.
Park S.J., Lee K.S., Lee S.J., Kim S.R., Park S.Y., Jeon M.S., Lee H.B., Lee Y.C. L-2-Oxothiazolidine-4-carboxylic acid or α-lipoic acid attenuates airway remodeling: Involvement of nuclear factor-κB (NF-κB), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and hypoxia-inducible factor (HIF). Int. J. Mol. Sci. 2012;13:7915-7937.
Not in our library10.3390/ijms13077915
153.
Shay K.P., Moreau R.F., Smith E.J., Smith A.R., Hagen T.M. Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Biochim. Biophys. Acta. 2009;1790:1149-1160.
Not in our library10.1016/j.bbagen.2009.07.026
154.
El-Gowelli H.M., Saad E.I., Abdel-Galil A.G.A., Ibrahim E.R. Co-administration of α-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX-2/miR-210 cascade. Toxicol. Appl. Pharmacol. 2015;288:300-312.
Not in our library10.1016/j.taap.2015.08.002
155.
Sahin K., Orhan C., Smith M.O., Sahin N. Molecular targets of dietary phytochemicals for the alleviation of heat stress in poultry. Worlds. Poult. Sci. J. 2013;69:113-124.
Not in our library10.1017/s004393391300010x
156.
Zhuang H., Kim Y.S., Koehler R.C., Doré S. Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann. N. Y. Acad. Sci. 2003;993:276-286.
Not in our library10.1111/j.1749-6632.2003.tb07534.x
157.
Liu L.L., He J.H., Xie H.B., Yang Y.S., Li J.C., Zou Y. Resveratrol induces antioxidant and heat shock protein mRNA expression in response to heat stress in black-boned chickens. Poult. Sci. 2014;93:54-62.
Not in our library10.3382/ps.2013-03423
158.
Cao S., Shen Z., Wang C., Zhang Q., Hong Q., He Y., Hu C. Resveratrol improves intestinal barrier function, alleviates mitochondrial dysfunction and induces mitophagy in diquat challenged piglets. Food Funct. 2019;10:344-354.
Not in our library10.1039/c8fo02091d
159.
Putics A., Végh E.M., Csermely P., Soti C. Resveratrol induces the heat-shock response and protects human cells from severe heat stress. Antioxid. Redox Signal. 2008;10:65-75.
Not in our library10.1089/ars.2007.1866
160.
Burkitt M.J., Duncan J. Effects of trans-resveratrol on copper-dependent hydroxyl-radical formation and DNA damage: Evidence for hydroxyl-radical scavenging and a novel, glutathione-sparing mechanism of action. Arch. Biochem. Biophys. 2000;381:253-263.
Not in our library10.1006/abbi.2000.1973
161.
Wang N., Han Q., Wang G., Ma W.P., Wang J., Wu W.X., Guo Y., Liu L., Jiang X.Y., Xie X.L., et al. Resveratrol protects oxidative stress-induced intestinal epithelial barrier dysfunction by upregulating heme oxygenase-1 expression. Dig. Dis. Sci. 2016;61:2522-2534.
Not in our library10.1007/s10620-016-4184-4
162.
Liu L., Fu C., Yan M., Xie H., Li S., Yu Q., He S., He J. Resveratrol modulates intestinal morphology and HSP70/90, NF-κB and EGF expression in the jejunal mucosa of black-boned chickens on exposure to circular heat stress. Food Funct. 2016;7:1329-1338.
Not in our library10.1039/c5fo01338k
163.
Ling K.H., Wan M.L.Y., El-Nezami H., Wang M. Protective capacity of resveratrol, a natural polyphenolic compound, against deoxynivalenol-induced intestinal barrier dysfunction and bacterial translocation. Chem. Res. Toxicol. 2016;9:823-833.
Not in our library10.1021/acs.chemrestox.6b00001
164.
Mayangsari Y., Suzuki T. Resveratrol ameliorates intestinal barrier defects and inflammation in colitic mice and intestinal cells. J. Agric. Food Chem. 2018;66:12666-12674.
Not in our library10.1021/acs.jafc.8b04138
165.
Jo H.A., Hwang D., Kim J.K., Lim Y.H. Oxyresveratrol improves tight junction integrity through the PKC and MAPK signaling pathways in Caco-2 cells. Food Chem. Toxicol. 2017;108:203-213.
Not in our library10.1016/j.fct.2017.08.002
166.
Yoo C.-G., Lee S., Lee C.-T., Kim Y.W., Han S.K., Shim Y.-S. Anti-inflammatory effect of heat shock protein induction is related to stabilization of IB through preventing IB kinase activation in respiratory epithelial cells. J. Immunol. 2000;164:5416-5423.
Not in our library10.4049/jimmunol.164.10.5416
167.
Rossi A., Coccia M., Trotta E., Angelini M., Santoro M.G. Regulation of cyclooxygenase-2 expression by heat: A novel aspect of heat shock factor 1 function in human cells. PLoS ONE. 2012;7:e31304.
Not in our library10.1371/journal.pone.0031304
168.
Sengottuvelan M., Deeptha K., Nalini N. Influence of dietary resveratrol on early and late molecular markers of 1,2-dimethylhydrazine-induced colon carcinogenesis. Nutrition. 2009;25:1169-1176.
Not in our library10.1016/j.nut.2009.03.009
169.
Sergent T., Piront N., Meurice J., Toussaint O., Schneider Y.J. Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem. Biol. Interact. 2010;188:659-667.
Not in our library10.1016/j.cbi.2010.08.007
170.
Szajewska H., Horvath A., Koletzko B. Effect of n-3 long-chain polyunsaturated fatty acid supplementation of women with low-risk pregnancies on pregnancy outcomes and growth measures at birth: A meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 2006;83:1337-1344.
Not in our library10.1093/ajcn/83.6.1337
171.
Yates C.M., Calder P.C., Ed Rainger G. Pharmacology and therapeutics of omega-3 polyunsaturated fatty acids in chronic inflammatory disease. Pharmacol. Ther. 2014;141:272-282.
Not in our library10.1016/j.pharmthera.2013.10.010
172.
Giordano E., Visioli F. Long-chain omega 3 fatty acids: Molecular bases of potential antioxidant actions. Prostaglandins Leukot. Essent. Fat. Acids. 2014;90:1-4.
Not in our library10.1016/j.plefa.2013.11.002
173.
Visioli F., Giordano E., Nicod N.M., Dávalos A. Molecular targets of omega 3 and conjugated linoleic fatty acids—“Micromanaging” cellular response. Front. Physiol. 2012;3:42.
Not in our library10.3389/fphys.2012.00042
174.
Brahmbhatt V., Oliveira M., Briand M., Perrisseau G., Bastic Schmid V., Destaillats F., Pace-Asciak C., Benyacoub J., Bosco N. Protective effects of dietary EPA and DHA on ischemia-reperfusion-induced intestinal stress. J. Nutr. Biochem. 2013;24:104-111.
Not in our library10.1016/j.jnutbio.2012.02.014
175.
Xiao G., Tang L., Yuan F., Zhu W., Zhang S., Liu Z., Geng Y., Qiu X., Zhang Y., Su L. Eicosapentaenoic acid enhances heat stress-impaired intestinal epithelial barrier function in Caco-2 cells. PLoS ONE. 2013;8:e73571.
Not in our library10.1371/journal.pone.0073571
176.
Beguin P., Errachid A., Larondelle Y., Schneider Y.J. Effect of polyunsaturated fatty acids on tight junctions in a model of the human intestinal epithelium under normal and inflammatory conditions. Food Funct. 2013;4:923-931.
Not in our library10.1039/c3fo60036j
177.
Cao W., Wang C., Chin Y., Chen X., Gao Y., Yuan S., Xue C., Wang Y., Tang Q. DHA-phospholipids (DHA-PL) and EPA-phospholipids (EPA-PL) prevent intestinal dysfunction induced by chronic stress. Food Funct. 2019;10:277-288.
Not in our library10.1039/c8fo01404c
178.
Grimble R.F. Basics in clinical nutrition: Immunonutrition—Nutrients which influence immunity: Effect and mechanism of action. e-SPEN Eur. e-J. Clin. Nutr. Metab. 2009;1:e10-e13.
Not in our library10.1016/j.eclnm.2008.07.015
179.
Zhao J., Shi P., Sun Y., Sun J., Dong J.-N., Wang H.-G., Zuo L.-G., Gong J.-F., Li Y., Gu L.-L., et al. DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function. Br. J. Nutr. 2015;114:181-188.
Not in our library10.1017/s0007114515001294
180.
Calviello G., Di Nicuolo F., Gragnoli S., Piccioni E., Serini S., Maggiano N., Tringali G., Navarra P., Ranelletti F.O., Palozza P. n-3 PUFAs reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE 2 induced ERK-1 and -2 and HIF-1α induction pathway. Carcinogenesis. 2004;25:2303-2310.
Not in our library10.1093/carcin/bgh265
181.
Narayanan B.A., Narayanan N.K., Simi B., Reddy B.S. Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells. Cancer Res. 2003;63:972-979.
Not in our library
182.
Omega-3 eicosapentaenoic acid decreases CD133 colon cancer stem-like cell marker expression while increasing sensitivity to chemotherapy. · 2013
Not checked
183.
Yang Y., Li W., Sun Y., Han F., Hu C.-A.A., Wu Z. Amino acid deprivation disrupts barrier function and induces protective autophagy in intestinal porcine epithelial cells. Amino Acids. 2015;47:2177-2184.
Not in our library10.1007/s00726-014-1844-6
184.
Genton L., Cani P.D., Schrenzel J. Alterations of gut barrier and gut microbiota in food restriction, food deprivation and protein-energy wasting. Clin. Nutr. 2015;34:341-349.
Not in our library10.1016/j.clnu.2014.10.003
185.
Brake J., Balnave D., Dibner J.J. Optimum dietary arginine:lysine ratio for broiler chickens is altered during heat stress in association with changes in intestinal uptake and dietary sodium chloride. Br. Poult. Sci. 1998;39:639-647.
Not in our library10.1080/00071669888511
186.
Wang W.W., Qiao S.Y., Li D.F. Amino acids and gut function. Amino Acids. 2009;37:105-110.
Not in our library10.1007/s00726-008-0152-4
187.
Morales A., Hernández L., Buenabad L., Avelar E., Bernal H., Baumgard L.H., Cervantes M. Effect of heat stress on the endogenous intestinal loss of amino acids in growing pigs. J. Anim. Sci. 2016;94:165-172.
Not in our library10.2527/jas.2015-9393
188.
Wang B., Wu Z., Ji Y., Sun K., Dai Z., Wu G. L-Glutamine enhances tight junction integrity by activating CaMK kinase 2–AMP-activated protein kinase signaling in intestinal porcine epithelial cells. J. Nutr. 2016;146:501-508.
Not in our library10.3945/jn.115.224857
189.
Marc Rhoads J., Wu G. Glutamine, arginine, and leucine signaling in the intestine. Amino Acids. 2009;37:111-122.
Not in our library10.1007/s00726-008-0225-4
190.
Grishin A., Bowling J., Bell B., Wang J., Ford H.R. Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis. J. Pediatr. Surg. 2016;51:13-17.
Not in our library10.1016/j.jpedsurg.2015.10.006
191.
Chen Y.-C., Liu Y.-C., Yen D.H.-T., Wang L.-M., Huang C.-I., Lee C.-H., Lin M.-T. L-Arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke. Shock. 2007;29:212-216.
Not in our library10.1097/shk.0b013e3180ca9ccc
192.
Chatterjee S., Premachandran S., Sharma D., Bagewadikar R.S., Poduval T.B. Therapeutic treatment with L-arginine rescues mice from heat stroke-induced death: Physiological and molecular mechanisms. Shock. 2005;24:341-347.
Not in our library10.1097/01.shk.0000180983.55623.2b
193.
Chang C.-K., Chang C.-P., Chiu W.-T., Lin M.-T. Prevention and repair of circulatory shock and cerebral ischemia/injury by various agents in experimental heatstroke. Curr. Med. Chem. 2006;13:3145-3154.
Not in our library10.2174/092986706778742945
194.
Sukhotnik I., Helou H., Mogilner J., Lurie M., Bernsteyn A., Coran A.G., Shiloni E. Oral arginine improves intestinal recovery following ischemia-reperfusion injury in rat. Pediatr. Surg. Int. 2005;21:191-196.
Not in our library10.1007/s00383-004-1318-0
195.
Tan B., Yin Y., Kong X., Li P., Li X., Gao H., Li X., Huang R., Wu G. L-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells. Amino Acids. 2010;38:1227-1235.
Not in our library10.1007/s00726-009-0334-8
196.
Rhoads J.M., Chen W., Gookin J., Wu G.Y., Fu Q., Blikslager T., Rippe R.A., Argenzio R.A., Cance W.G., Weaver E.M., et al. Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanism. Gut. 2004;53:514-522.
Not in our library10.1136/gut.2003.027540
197.
Sharma J.N., Al-Omran A., Parvathy S.S. Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2007;15:252-259.
Not in our library10.1007/s10787-007-0013-x
198.
Kozar R.A., Verner-Cole E., Schultz S.G., Sato N., Bick R.J., Desoignie R., Poindexter B.J., Moore F.A. The immune-enhancing enteral agents arginine and glutamine differentially modulate gut barrier function following mesenteric ischemia/reperfusion. J. Trauma. 2004;57:1150-1156.
Not in our library10.1097/01.ta.0000151273.01810.e9
199.
Morris S.M. Enzymes of arginine metabolism. J. Nutr. 2004;134:2743-2747.
Not in our library10.1093/jn/134.10.2743s
200.
Rhoads J.M., Liu Y., Niu X., Surendran S., Wu G. Arginine stimulates cdx2-transformed intestinal epithelial cell migration via a mechanism requiring both nitric oxide and phosphorylation of p70 S6 kinase. J. Nutr. 2008;138:1652-1657.
Not in our library10.1093/jn/138.9.1652
201.
Inoue T., Kwon A., Oda M., Kaibori M., Kamiyama Y., Nishizawa M., Ito S., Okumura T. Hypoxia and heat inhibit inducible nitric oxide synthase gene expression by different mechanisms in rat hepatocytes. Hepatology. 2000;32:1037-1044.
Not in our library10.1053/jhep.2000.18715
202.
Costa K.A., Soares A.D., Wanner S.P., Santos R.D., Fernandes S.O., Martins F.D., Nicoli J.R., Coimbra C.C., Cardoso V.N. L-Arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male swiss mice subjected to physical exercise under environmental heat stress. J. Nutr. 2014;144:218-223.
Not in our library10.3945/jn.113.183186
203.
Lacerda A.C.R., Marubayashi U., Coimbra C.C. Nitric oxide pathway is an important modulator of heat loss in rats during exercise. Brain Res. Bull. 2005;67:110-116.
Not in our library10.1016/j.brainresbull.2005.06.002
204.
Quirino I.E., Cardoso V.N., Santos R.D., Evangelista W.P., Arantes R.M., Fiúza J.A., Glória M.B., Alvarez-Leite J.I., Batista M.A., Correia M.I.T.D. The role of L-arginine and inducible nitric oxide synthase in intestinal permeability and bacterial translocation. J. Parenter. Enter. Nutr. 2013;37:392-400.
Not in our library10.1177/0148607112458325
205.
Bailey S.J., Winyard P.G., Vanhatalo A., Blackwell J.R., DiMenna F.J., Wilkerson D.P., Jones A.M. Acute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise tolerance. J. Appl. Physiol. 2010;109:1394-1403.
Not in our library10.1152/japplphysiol.00503.2010
206.
Vanhatalo A., Fulford J., Bailey S.J., Blackwell J.R., Winyard P.G., Jones A.M. Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia. J. Physiol. 2011;589:5517-5528.
Not in our library10.1113/jphysiol.2011.216341
207.
L-arginine Supplementation Improves Responses to Injury and Inflammation in Dextran Sulfate Sodium Colitis · 2012
No notice
208.
Chapman J.C., Liu Y., Zhu L., Rhoads J.M. Arginine and citrulline protect intestinal cell monolayer tight junctions from hypoxia-induced injury in piglets. Pediatr. Res. 2012;72:576-582.
Not in our library10.1038/pr.2012.137
209.
Tanaka A., Mizoguchi H., Kunikata T., Miyazawa T., Takeuchi K. Protection by constitutively formed nitric oxide of intestinal damage induced by indomethacin in rats. J. Physiol. Paris. 2001;95:35-41.
Not in our library10.1016/s0928-4257(01)00007-9
210.
Viana M., Santos R.G., Generoso S.V., Arantes R.M., Correia M.I., Cardoso V.N. Pretreatment with arginine preserves intestinal barrier integrity and reduces bacterial translocation in mice. Nutrition. 2010;26:218-223.
Not in our library10.1016/j.nut.2009.04.005
211.
Morris S.M. Arginine metabolism: Boundaries of our knowledge. J. Nutr. 2007;137:1602-1609.
Not in our library10.1093/jn/137.6.1602s
212.
Singer I.I., Kawka D.W., Scott S., Weidner J.R., Mumford R.A., Riehl T.E., Stenson W.F. Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology. 1996;111:871-885.
Not in our library10.1016/s0016-5085(96)70055-0
213.
Marcinkiewicz E.W.A., Opicki S.C.H., Marcinkiewicz J. Nitric oxide—A pro-inflammatory and anti-inflammatory mediator. Cent. Eur. J. Immunol. 2003;28:74-78.
Not in our library
214.
Katsube T., Tsuji H., Onoda M. Nitric oxide attenuates hydrogen peroxide-induced barrier disruption and protein tyrosine phosphorylation in monolayers of intestinal epithelial cell. Biochim. Biophys. Acta. 2007;1773:794-803.
Not in our library10.1016/j.bbamcr.2007.03.002
215.
Sheth P., Seth A., Atkinson K.J., Gheyi T., Kale G., Giorgianni F., Desiderio D.M., Li C., Naren A., Rao R. Acetaldehyde dissociates the PTP1B-E-cadherin-beta-catenin complex in Caco-2 cell monolayers by a phosphorylation-dependent mechanism. Biochem. J. 2007;402:291-300.
Not in our library10.1042/bj20060665
216.
Maher P.A., Pasquale E.B. Heat shock induces protein tyrosine phosphorylation in cultured cells. J. Cell Biol. 1989;108:2029-2035.
Not in our library10.1083/jcb.108.6.2029
217.
Gookin J.L., Rhoads J.M., Argenzio R.A. Inducible nitric oxide synthase mediates early epithelial repair of porcine ileum. Am. J. Physiol. Gastrointest. Liver Physiol. 2002;283:157-168.
Not in our library10.1152/ajpgi.00005.2001
218.
Corl B.A., Odle J., Niu X., Moeser A.J., Gatlin L.A., Phillips O.T., Blikslager A.T., Rhoads J.M. Arginine activates intestinal p70(S6k) and protein synthesis in piglet rotavirus enteritis. J. Nutr. 2008;138:24-29.
Not in our library10.1093/jn/138.1.24
219.
Ban H., Shigemitsu K., Yamatsuji T., Haisa M., Nakajo T., Takaoka M., Nobuhisa T., Gunduz M., Tanaka N., Naomoto Y. Arginine and Leucine regulate p70 S6 kinase and 4E-BP1 in intestinal epithelial cells. Int. J. Mol. Med. 2004;13:537-543.
Not in our library10.3892/ijmm.13.4.537
220.
Wang J.Y. Polyamines regulate expression of E-cadherin and play an important role in control of intestinal epithelial barrier function. Inflammopharmacology. 2005;13:91-101.
Not in our library10.1163/156856005774423890
221.
Iwashita Y., Sakiyama T., Musch M.W., Ropeleski M.J., Tsubouchi H., Chang E.B. Polyamines mediate glutamine-dependent induction of the intestinal epithelial heat shock response. Am. J. Physiol. Gastrointest. Liver Physiol. 2011;301:181-187.
Not in our library10.1152/ajpgi.00054.2011
222.
Rhee H.J., Kim E.J., Lee J.K. Physiological polyamines: Simple primordial stress molecules. J. Cell. Mol. Med. 2007;11:685-703.
Not in our library10.1111/j.1582-4934.2007.00077.x
223.
Viana M.L., Dos Santos R.D., Generoso S.D.V., Nicoli J.R., Martins F.D.S., Nogueira-Machado J.A., Arantes R.M., Correia M.I., Cardoso V.N. The role of l-arginine-nitric oxide pathway in bacterial translocation. Amino Acids. 2013;45:1089-1096.
Not in our library10.1007/s00726-013-1558-1
224.
Connelly L., Palacios-Callender M., Ameixa C., Moncada S., Hobbs A.J. Biphasic regulation of NF-kappa B activity underlies the pro- and anti-inflammatory actions of nitric oxide. J. Immunol. 2001;166:3873-3881.
Not in our library10.4049/jimmunol.166.6.3873
225.
Yi G.F., Allee G.L., Knight C.D., Dibner J.J. Impact of glutamine and Oasis hatchling supplement on growth performance, small intestinal morphology, and immune response of broilers vaccinated and challenged with Eimeria maxima. Poult. Sci. 2005;84:283-293.
Not in our library10.1093/ps/84.2.283
226.
Wu G. Functional amino acids in growth, reproduction, and health. Adv. Nutr. 2010;1:31-37.
Not in our library10.3945/an.110.1008
227.
Windmueller H.G., Spaeth A.E. Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for postabsorptive rat small intestine. J. Biol. Chem. 1978;253:69-76.
Not in our library
228.
Daniele B., Perrone F., Gallo C., Pignata S., De Martino S., De Vivo R., Barletta E., Tambaro R., Abbiati R., D’Agostino L. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: A double blind, placebo controlled, randomised trial. Gut. 2001;48:28-33.
Not in our library10.1136/gut.48.1.28
229.
Dai S.F., Gao F., Xu X.L., Zhang W.H., Song S.X., Zhou G.H. Effects of dietary glutamine and gamma-aminobutyric acid on meat colour, pH, composition, and water-holding characteristic in broilers under cyclic heat stress. Br. Poult. Sci. 2012;53:471-481.
Not in our library10.1080/00071668.2012.719148
230.
Ulluwishewa D., Anderson R.C., McNabb W.C., Moughan P.J., Wells J.M., Roy N.C. Regulation of tight junction permeability by intestinal bacteria and dietary components. J. Nutr. 2011;141:769-776.
Not in our library10.3945/jn.110.135657
231.
Li P., Yin Y., Li D., Kim S.W., Wu G. Review Article: Amino acids and immune function. Br. J. Nutr. 2007;98:237-252.
Not in our library10.1017/s000711450769936x
232.
Wischmeyer P.E., Musch M.W., Madonna M.B., Thisted R., Chang E.B. Glutamine protects intestinal epithelial cells: Role of inducible HSP70. Am. J. Physiol. 1997;272:G879-G884.
Not in our library10.1152/ajpgi.1997.272.4.g879
233.
Ropeleski M.J., Riehm J., Baer K.A., Musch M.W., Chang E.B. Anti-apoptotic effects of L-glutamine-mediated transcriptional modulation of the heat shock protein 72 during heat shock. Gastroenterology. 2005;129:170-184.
Not in our library10.1053/j.gastro.2005.05.017
234.
Phanvijhitsiri K., Musch M.W., Ropeleski M.J., Chang E.B. Heat induction of heat shock protein 25 requires cellular glutamine in intestinal epithelial cells. Am. J. Physiol. Cell Physiol. 2006;291:C290-C299.
Not in our library10.1152/ajpcell.00225.2005
235.
Zhou Q., Souba W.W., Croce C.M., Verne G.N. MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut. 2010;59:775-784.
Not in our library10.1136/gut.2009.181834
236.
Chaudhry K.K., Shukla P.K., Mir H., Manda B., Gangwar R., Yadav N., McMullen M., Nagy L.E., Rao R.K. Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice. J. Nutr. Biochem. 2016;27:16-26.
Not in our library10.1016/j.jnutbio.2015.08.012
237.
Bertrand J., Ghouzali I., Guérin C., Bôle-Feysot C., Gouteux M., Déchelotte P., Ducrotté P., Coëffier M. Glutamine restores tight junction protein Claudin-1 expression in colonic mucosa of patients with diarrhea-predominant irritable bowel syndrome. J. Parenter. Enter. Nutr. 2016;40:1170-1176.
Not in our library10.1177/0148607115587330
238.
Shakeri M., Zulkifli I., Soleimani A.F., O’Reilly E.L., Eckersall P.D., Anna A.A., Kumari S., Abdullah F.F.J. Environment, well-being, and behavior: Response to dietary supplementation of L-glutamine and L-glutamate in broiler chickens reared at different stocking densities under hot, humid tropical conditions. Poult. Sci. 2014;93:2700-2708.
Not in our library10.3382/ps.2014-03910
239.
Wu G., Meier S.A., Knabe D.A. Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. J. Nutr. 1996;126:2578-2584.
Not in our library10.1093/jn/126.10.2578
240.
Li N., Lewis P., Samuelson D., Liboni K., Neu J. Glutamine regulates Caco-2 cell tight junction proteins. Am. J. Physiol. Liver Physiol. 2004;287:G726-G733.
Not in our library10.1152/ajpgi.00012.2004
241.
Li N., DeMarco V.G., West C.M., Neu J. Glutamine supports recovery from loss of transepithelial resistance and increase of permeability induced by media change in Caco-2 cells. J. Nutr. Biochem. 2003;14:401-408.
Not in our library10.1016/s0955-2863(03)00071-8
242.
Gu X.H., Hao Y., Wang X.L. Overexpression of heat shock protein 70 and its relationship to intestine under acute heat stress in broilers: 2. Intestinal oxidative stress. Poult. Sci. 2012;91:790-799.
Not in our library10.3382/ps.2011-01628
243.
Zuhl M.N., Lanphere K.R., Kravitz L., Mermier C.M., Schneider S., Dokladny K., Moseley P.L. Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression. J. Appl. Physiol. 2014;116:183-191.
Not in our library10.1152/japplphysiol.00646.2013
244.
Akagi R., Ohno M., Matsubara K., Fujimoto M., Nakai A., Inouye S. Glutamine protects intestinal barrier function of colon epithelial cells from ethanol by modulating Hsp70 expression. Pharmacology. 2013;91:104-111.
Not in our library10.1159/000345930
245.
Giriş M., Erbil Y., Öztezcan S., Olgaç V., Barbaros U., Deveci U., Kirgiz B., Uysal M., Toker G.A. The effect of heme oxygenase-1 induction by glutamine on radiation-induced intestinal damage: The effect of heme oxygenase-1 on radiation enteritis. Am. J. Surg. 2006;191:503-509.
Not in our library10.1016/j.amjsurg.2005.11.004
246.
Seth A., Basuroy S., Sheth P., Rao R.K. L-Glutamine ameliorates acetaldehyde-induced increase in paracellular permeability in Caco-2 cell monolayer. Am. J. Physiol. Liver Physiol. 2004;287:G510-G517.
Not in our library10.1152/ajpgi.00058.2004
247.
Li N., Neu J. Glutamine deprivation alters intestinal tight junctions via a PI3-K/Akt mediated pathway in Caco-2 cells. J. Nutr. 2009;139:710-714.
Not in our library10.3945/jn.108.101485
248.
Beutheu S., Ghouzali I., Galas L., Déchelotte P., Coëffier M. Glutamine and arginine improve permeability and tight junction protein expression in methotrexate-treated Caco-2 cells. Clin. Nutr. 2013;32:863-869.
Not in our library10.1016/j.clnu.2013.01.014
249.
Coëffier M., Marion R., Ducrotté P., Déchelotte P. Modulating effect of glutamine on IL-1β-induced cytokine production by human gut. Clin. Nutr. 2003;22:407-413.
Not in our library10.1016/s0261-5614(03)00040-2
250.
Li N., Liboni K., Fang M.Z., Samuelson D., Lewis P., Patel R., Neu J. Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant rats. Am. J. Physiol. Liver Physiol. 2004;286:G914-G921.
Not in our library10.1152/ajprenal.00073.2004
251.
Cöeffier M., Marion-Letellier R., Déchelotte P. Potential for amino acids supplementation during inflammatory bowel diseases. Inflamm. Bowel Dis. 2010;16:518-524.
Not in our library10.1002/ibd.21017
252.
Zhou Y., Zhang P., Deng G., Liu X., Lu D. Improvements of immune status, intestinal integrity and gain performance in the early-weaned calves parenterally supplemented with l-alanyl-l-glutamine dipeptide. Vet. Immunol. Immunopathol. 2012;145:134-142.
Not in our library10.1016/j.vetimm.2011.10.020
253.
Wu Q.J., Liu N., Wu X.H., Wang G.Y., Lin L. Glutamine alleviates heat stress-induced impairment of intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers. Poult. Sci. 2018;97:2675-2683.
Not in our library10.3382/ps/pey123
254.
Lesueur C., Bôle-Feysot C., Bekri S., Husson A., Lavoinne A., Brasse-Lagnel C. Glutamine induces nuclear degradation of the NF-κB p65 subunit in Caco-2/TC7 cells. Biochimie. 2012;94:806-815.
Not in our library10.1016/j.biochi.2011.11.012
255.
Chatterjee A., Snead C., Yetik-Anacak G., Antonova G., Zeng J., Catravas J.D. Heat shock protein 90 inhibitors attenuate LPS-induced endothelial hyperpermeability. Am. J. Physiol. Lung Cell. Mol. Physiol. 2008;294:L755-L763.
Not in our library10.1152/ajplung.00350.2007
256.
Fanelli M.A., Montt-Guevara M., Diblasi A.M., Gago F.E., Tello O., Cuello-Carrión F.D., Callegari E., Bausero M.A., Ciocca D.R. P-Cadherin and β-catenin are useful prognostic markers in breast cancer patients; β-catenin interacts with heat shock protein Hsp27. Cell Stress Chaperones. 2008;13:207-220.
Not in our library10.1007/s12192-007-0007-z
257.
Shinde T., Perera A.P., Vemuri R., Gondalia S.V., Karpe A.V., Beale D.J., Shastri S., Southam B., Eri R., Stanley R. Synbiotic supplementation containing whole plant sugar cane Fibre and probiotic spores potentiates protective synergistic effects in mouse model of IBD. Nutrients. 2019;11:818.
Not in our library10.3390/nu11040818
258.
Salberg S., Yamakawa G., Christensen J., Kolb B., Mychasiuk R. Assessment of a nutritional supplement containing resveratrol, prebiotic fiber, and omega-3 fatty acids for the prevention and treatment of mild traumatic brain injury in rats. Neuroscience. 2017;365:146-157.
Not in our library10.1016/j.neuroscience.2017.09.053

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Intestinal Barrier in Human Health and Disease · 2021
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