CD8+T cell infiltration-associated barrier function of brain endothelial cells is enhanced by Astragalus polysaccharides via inhibiting PI3K/AKT signaling pathway.

Pathogenic CD8+T cells play an essential role in neuroinflammation and neural injury, which leads to the progression of inflammatory neurological disorders. Thus, blocking the infiltration of CD8+T cells is necessary for the treatment of neuroinflammatory diseases. Our previous study demonstrated that Astragalus polysaccharides (APS) could significantly reduce the infiltration of CD8+T cells in experimental autoimmune encephalomyelitis (EAE) mice. However, the mechanism by which APS suppress CD8+T cell infiltration remains elusive. In this study, we further found that APS could reduce the CD8+T cell infiltration in EAE and lipopolysaccharide (LPS)-induced neuroinflammatory model. Furthermore, we established the mouse brain endothelial cell (bEnd.3) inflammatory injury model by interleukin-1ß (IL-1ß) or LPS in vitro. The results showed that APS treatment downregulated the expression of vascular cell adhesion molecule1 (VCAM1) to decrease the adhesion of CD8+T cells to bEnd.3 cells. APS also upregulated the expression of zonula occluden-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) to reduce the trans-endothelial migration of CD8+T cells. The PI3K/AKT signaling pathway might mediate this protective effect of APS on bEnd.3 cells against inflammatory injury. In addition, we demonstrated the protective effect of APS on the integrity of brain endothelial cells in an LPS-induced neuroinflammatory model. In summary, our results indicate that APS can reduce peripheral CD8+T cell infiltration via enhancing the barrier function of brain endothelial cells, it may be a potential for the prevention of neuroinflammatory diseases.

Validation of an in vivo dual permeability marker technique to characterize regional gastrointestinal tract permeability in mid lactation Holstein cows during short-term feed restriction.

This study evaluated the impact of short-term feed restriction in lactating dairy cows on regional permeability of the gastrointestinal tract (GIT), and the recovery of DMI, ruminal pH, and milk yield. In addition, sampling methods for a novel dual marker technique to characterize total GIT and post ruminal permeability were validated. Six ruminally cannulated lactating Holstein cows were blocked by parity (3 primiparous, 3 multiparous; 189 DIM ± 25.2) and enrolled in a crossover design. Experimental periods included a 5-d baseline phase (BASE), 5-d challenge phase (CHAL), and 2 weeks of recovery (REC1 and REC2). During CHAL cows received either 100% ad libitum feed intake (AL) or 40% of ad libitum feed intake (FR). To assess, total-tract and post-ruminal permeability, equimolar doses of Cr-EDTA and Co-EDTA were infused on d 3 of CHAL into the rumen and abomasum (0.369 mmol/kg BW). Following infusions, total urine and feces were collected every 8 h over 96 h, and blood samples were collected at h 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, and 64. The plasma area under the curve (AUC) for Cr and Co were calculated. By design, DMI for FR was reduced by 60% during CHAL and remained 19% lower than AL during REC1 but was not different from AL in REC2. Mean ruminal pH for FR was greatest during CHAL and the least during REC1, with no differences detected between AL and FR in REC2. The duration that pH was < 5.8 was the least for FR during CHAL and greatest during REC1 which were different from AL and were no longer different between treatments in REC2. Milk yield was the least for FR during CHAL and REC1 and no longer different from AL in REC2. Feed restriction reduced milk fat, protein, and lactose yields by 26, 31% and 31%, respectively. Plasma Cr AUC was 34% greater and Co AUC tended to be 35% greater for FR than AL on d 3 of CHAL. Urinary Cr recovery after 48-h was not affected by treatment; however, urinary Co recovery was 36% greater for FR than AL. Positive correlations between plasma AUC and urinary recovery for Cr and Co were detected. It was determined that blood samples collected at h 2, 8, 20, 40, and 48 could predict the total plasma Cr and Co AUC within 1.9% and 6.2%, respectively. In summary, short-term FR in lactating dairy cows increases permeability of the total GIT and may increase permeability of the post-ruminal regions with more than 60% of the permeability occurring post-ruminally. After FR, cows experienced low ruminal pH and a sustained reduction in milk yield. When utilizing Cr- and Co-EDTA to evaluate regional GIT permeability, plasma AUC can be used as an alternate to urinary Cr and Co excretion. In addition, blood samples collected at h 2, 8, 20, 40, and 48 result in adequate prediction accuracy, at least when comparing GIT permeability for lactating dairy cows exposed to AL and FR.

Intestinal permeability in disorders of gut-brain interaction (DGBI): From bench to bedside.

Intestinal barrier function lies at a critical interface of a range of peripheral and central processes that influence disorders of gut brain interactions (DGBI). While rigorously tested, the role of barrier dysfunction in driving clinical phenotype of DGBI remains to be fully elucidated. In vitro, in vivo and ex vivo strategies can test various aspects of the broader permeability and barrier mechanisms in the gut. Luminal mediators of host, bacterial and dietary origin can influence the barrier function and a disrupted barrier can also influence the luminal milieu. Critical to our understanding is how barrier dysfunction is influenced by stress and other comorbidities that associate with DGBI and the crosstalk between barrier and neural, hormonal, and immune responses . Additionally, the microbiome's significant role in the communication between the brain and gut has led to the integrative model of a microbiome gut brain axis with reciprocal interactions between brain networks and networks comprised of multiple cells in the gut, including immune cells, enterochromaffin cells, gut microbiota and the derived luminal mediators. This review highlights the techniques for assessment of barrier function, appraises evidence for barrier dysfunction in DGBI including mechanistic studies in humans as well as provides an overview of therapeutic strategies that can be used to directly or indirectly restore barrier function in DGBI patients.

Derivatives of postbiotics (cell wall constituents) from Bacillus subtilis (LCBS1) relieve soybean meal-induced enteritis in bullfrog (Aquarana catesbeianus).

Soybean meal (SM) serves as a primary alternative to fish meal in aquafeeds. However, a high-SM diet may result in intestinal injury. Our previous study demonstrated the probiotic effects of heat-inactivated Bacillus subtilis (LCBS1) on bullfrogs (Aquarana catesbeianus) fed a high-SM diet, probably attributed to the bioactive constituent of cell wall. Therefore, in this study, the main constituents of cell wall from LCBS1, including peptidoglycan (PGN), lipoteichoic acid (LTA), cell wall protein (CWP), and whole cell wall (WCW), were extracted and added to a high-SM (~55 %) diet to investigate their probiotic effects on bullfrogs and reveal the possible mechanisms. The results indicated that bullfrogs fed the LTA of LCBS1 showed the highest weight gain, feed efficiency, and protein efficiency ratio. Additionally, the LTA of LCBS1 could activate the humoral immunity and modulate intestinal microbiota. It might activate JAK2-STAT3 and MAPK-ERK pathways, as well as up-regulate tlr5 gene to promote intestinal cell proliferation, thereby alleviating jejunal injury. The WCW of LCBS1 effectively increased the growth performance of bullfrogs by improving the humoral immunity, enhancing intestinal barrier function, and alleviating intestinal inflammatory response. The PGN and CWP of LCBS1 could stimulate the humoral immunity and enhance intestinal barrier function, but had no significant effect on the growth performance of bullfrogs. In conclusion, the LTA might be the primary bioactive constituent of heat-inactivated LCBS1, with the beneficial effects of promoting intestinal cell proliferation and enhancing intestinal barrier function, therefore alleviating the intestinal injury induced by SM on bullfrogs. This study establishes a theoretical basis for the efficient utilization of plant proteins by the application of postbiotics additive in aquafeed, which further saves the feed costs and promotes development of economically sustainable aquaculture.

Molybdenum Nanoparticles Alleviate MC903-Induced Atopic Dermatitis-Like Symptoms in Mice by Modulating the ROS-Mediated NF-κB and Nrf2 /HO-1 Signaling Pathways.

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin condition that can affect individuals of all ages. Recent research has shown that oxidative stress plays a crucial role in the development of AD. Therefore, inhibiting oxidative stress may be an effective therapeutic approach for AD. Nano-molybdenum is a promising material for use as an antioxidant. We aimed to evaluate the therapeutic effects and preliminary mechanisms of molybdenum nanoparticles (Mo NPs) by using a murine model of chemically induced AD-like disease. Methods: HaCaT cells, a spontaneously immortalized human keratinocyte cell line, were stimulated by tumor necrosis factor-alpha /interferon-gamma after pre-treatment with Mo NPs. Reactive oxygen species levels, production of inflammatory factors, and activation of the nuclear factor kappa-B and the nuclear factor erythroid 2-related factor pathways were then evaluated. Mo NPs was topically applied to treat a murine model of AD-like disease induced by MC903, a vitamin D3 analog. Dermatitis scores, pruritus scores, transepidermal water loss and body weight were evaluated. AD-related inflammatory factors and chemokines were evaluated. Activation of the nuclear factor kappa-B and nuclear factor erythroid 2-related factor / heme oxygenase-1 pathways was assessed. Results: Our data showed that the topical application of Mo NPs dispersion could significantly alleviate AD skin lesions and itching and promote skin barrier repair. Further mechanistic experiments revealed that Mo NPs could inhibit the excessive activation of the nuclear factor kappa-B pathway, promote the expression of nuclear factor erythroid 2-related factor and heme oxygenase-1 proteins, and suppress oxidative stress reactions. Additionally, they inhibited the expression of thymic stromal lymphopoietin, inflammatory factors, and chemokines, thereby alleviating skin inflammation. Conclusion: Mo NPs present a promising alternative treatment option for patients with AD as they could address three pivotal mechanisms in the pathogenesis of AD concurrently.

The Skin Acid Mantle: An Update on Skin pH.

The acid mantle concept refers to the buffer system located in the upper stratum corneum of the skin. By sustaining an acidic environment, the acid mantle contributes to the regulation of the microbiome, structural stability, and inflammation. Skin pH is pivotal in maintaining the integrity of the epidermal barrier. Shifts in pH can disrupt barrier properties, and recent studies have emphasized its impact on dermatologic disease processes. This review explores the complex relationship of mechanisms through which skin pH impacts dermatologic pathologies. Furthermore, we highlight the promising potential of pH-targeted therapies for advancing the management of skin conditions.

Extracellular purines in lung endothelial permeability and pulmonary diseases.

The purinergic signaling system is an evolutionarily conserved and critical regulatory circuit that maintains homeostatic balance across various organ systems and cell types by providing compensatory responses to diverse pathologies. Despite cardiovascular diseases taking a leading position in human morbidity and mortality worldwide, pulmonary diseases represent significant health concerns as well. The endothelium of both pulmonary and systemic circulation (bronchial vessels) plays a pivotal role in maintaining lung tissue homeostasis by providing an active barrier and modulating adhesion and infiltration of inflammatory cells. However, investigations into purinergic regulation of lung endothelium have remained limited, despite widespread recognition of the role of extracellular nucleotides and adenosine in hypoxic, inflammatory, and immune responses within the pulmonary microenvironment. In this review, we provide an overview of the basic aspects of purinergic signaling in vascular endothelium and highlight recent studies focusing on pulmonary microvascular endothelial cells and endothelial cells from the pulmonary artery vasa vasorum. Through this compilation of research findings, we aim to shed light on the emerging insights into the purinergic modulation of pulmonary endothelial function and its implications for lung health and disease.

Alginate Oligosaccharides Enhance Antioxidant Status and Intestinal Health by Modulating the Gut Microbiota in Weaned Piglets.

Alginate oligosaccharides (AOSs), which are an attractive feed additive for animal production, exhibit pleiotropic bioactivities. In the present study, we investigated graded doses of AOS-mediated alterations in the physiological responses of piglets by determining the intestinal architecture, barrier function, and microbiota. A total of 144 weaned piglets were allocated into four dietary treatments in a completely random design, which included a control diet (CON) and three treated diets formulated with 250 mg/kg (AOS250), 500 mg/kg (AOS500), and 1000 mg/kg AOS (AOS1000), respectively. The trial was carried out for 28 days. Our results showed that AOS treatment reinforced the intestinal barrier function by increasing the ileal villus height, density, and fold, as well as the expression of tight junction proteins, especially at the dose of 500 mg/kg AOS. Meanwhile, supplementations with AOSs showed positive effects on enhancing antioxidant capacity and alleviating intestinal inflammation by elevating the levels of antioxidant enzymes and inhibiting excessive inflammatory cytokines. The DESeq2 analysis showed that AOS supplementation inhibited the growth of harmful bacteria Helicobacter and Escherichia_Shigella and enhanced the relative abundance of Faecalibacterium and Veillonella. Collectively, these findings suggested that AOSs have beneficial effects on growth performance, antioxidant capacity, and gut health in piglets.

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis. Peroxisome proliferator activated receptor (PPAR) α and δ play a key role in lipid metabolism and intestinal barrier homeostasis, which are major contributors to the pathological progression of ALD. Meanwhile, elafibranor (EFN), which is a dual PPARα and PPARδ agonist, has reached a phase III clinical trial for the treatment of metabolic dysfunction-associated steatotic liver disease and primary biliary cholangitis. However, the benefits of EFN for ALD treatment is unknown. AIM: To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model. METHODS: ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) for 8 weeks. EFN (3 and 10 mg/kg/day) was orally administered during the experimental period. Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis, fibrosis, and intestinal barrier integrity. The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays. RESULTS: The hepatic steatosis, apoptosis, and fibrosis in the ALD mice model were significantly attenuated by EFN treatment. EFN promoted lipolysis and ß-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells, primarily through PPARα activation. Moreover, EFN inhibited the Kupffer cell-mediated inflammatory response, with blunted hepatic exposure to lipopolysaccharide (LPS) and toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses. The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation. CONCLUSION: EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis, enhancing hepatocyte autophagic and antioxidant capacities, and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Astragalus polysaccharides-induced gut microbiota play a predominant role in enhancing of intestinal barrier function of broiler chickens.

BACKGROUND: The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota. Astragalus polysaccharides (APS) have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function. The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed. RESULTS: Dietary polysaccharide deprivation induced intestinal barrier dysfunction, decreased growth performance, altered microbial composition (Faecalibacterium, Dorea, and Coprobacillus), and reduced isobutyrate concentration. The results showed that APS facilitates intestinal barrier function in broiler chickens, including a thicker mucus layer, reduced crypt depth, and the growth of tight junction proteins. We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides, a commensal bacterium that plays a predominant role in enhancing intestinal barrier function. An in vitro growth assay further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis. Dietary APS supplementation increased the concentrations of isobutyrate and bile acid (mainly chenodeoxycholic acid and deoxycholate acid) and activated signaling pathways related to intestinal barrier function (such as protein processing in the endoplasmic reticulum, tight junctions, and adherens junction signaling pathways). CONCLUSIONS: APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis, and increasing the concentrations of isobutyrate and bile acids (mainly CDCA and DCA). These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.

Clinical efficacy of 595 nm pulsed dye laser in combination with supramolecular salicylic acid in the treatment of rosacea.

OBJECTIVE: This research was aimed at ascertaining the clinical effects of 595 nm pulsed dye laser (PDL) in combination with supramolecular salicylic acid (SSA) in the treatment of rosacea. METHODS: Eighty-four patients with rosacea were selected, of which 42 patients treated with PDL alone were considered as the control group, and 42 patients treated with 595 nm PDL in combination with 30% SSA were regarded as the observation group. The treatment continued for 4 months in the two groups. Clinical symptom scores, skin barrier function indicators, serum inflammatory factors, Acne⁃QOL scores and adverse reactions between the two groups were compared. RESULTS: After treatment, levels of inflammatory factors, clinical symptom scores, transdermal water loss, and oil volume were decreased, and epidermal water content and Acne-QOL scores were increased in both groups (all P < 0.05), and the changes in the observation group were more pronounced versus the control group (all P < 0.05). The difference in the incidence of adverse reactions was not statistically significant between the two groups (P > 0.05). CONCLUSION: 595 nm PDL in combination with SSA is safe in the treatment of rosacea.

GSK3ß Substrate-competitive Inhibitors Regulate the gut Homeostasis and Barrier Function to Inhibit Neuroinflammation in Scopolamine-induced Alzheimer's Disease Model Mice.

Alzheimer's disease (AD) is a neurodegenerative disease mainly characterized by cognitive impairment. Glycogen synthase kinase 3 (GSK3ß) is a potential therapeutic target against AD. Isoorientin (ISO), a GSK3ß substrate competitive inhibitor, plays anti-AD effects in in vitro and in vivo AD model. TFGF-18 is an ISO synthetic analog with improved potency, but its neuroprotective effect in vivo remains to be elucidated, and the underlying mechanisms of GSK3ß inhibitor against AD need to be clarified. This study investigated the TFGF-18 and ISO effects on gut homeostasis and neuroinflammation in scopolamine (SCOP)-induced AD mice. And the protection on barrier function was observed in in vitro blood-brain barrier (BBB) model of mouse brain microvascular endothelial cells (bEnd.3). The results show that TFGF-18 and ISO improved cognitive function in SCOP-induced mice, and inhibited cholinergic system disorders and inflammation in the brain and intestine, decreased the level of lipopolysaccharides (LPS) in serum and intestine, protected the diversity and balance of intestinal microbiome, increased the expressions of tight junction protein (ZO-1, occludin), brain derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the mouse brain and intestine. In addition, TFGF-18 and ISO protected against barrier damage in LPS-stimulated BBB model of bEnd.3 cells in vitro. TFGF-18 and ISO increased the ratio of p-GSK3ß/GSK3ß, suppressed toll-like receptors 4 (TLR-4) expression and nuclear factor kappa-B (NF-κB) activation in vivo and in vitro, and increased the expressions of ß-catenin, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in vitro. In conclusion, The GSK3ß inhibitors TFGF-18 and ISO modulate the gut homeostasis and barrier function to inhibit neuroinflammation and attenuate cognitive impairment by regulating NF-κB, ß-catenin and Nrf2/HO-1 pathways.

The role of fiber in modulating plant protein-induced metabolic responses.

The rising consumption of plant protein foods and the emergence of meat alternatives have prompted interest in the health benefits of such products, which contain fiber in addition to protein. This review investigates the effect of fiber on plant-based protein metabolism and evaluates its contribution to gut-derived health impacts. Plant proteins, which often come with added fiber, can have varying health outcomes. Factors such as processing and the presence of fiber and starch influence the digestibility of plant proteins, potentially leading to increased proteolytic fermentation in the gut and the production of harmful metabolites. However, fermentable fiber can counteract this effect by serving as a primary substrate for gut microbes, decreasing proteolytic activity. The increased amount of fiber, rather than the protein source itself, plays a significant role in the observed health benefits of plant-based diets in human studies. Differences between extrinsic and intrinsic fiber in the food matrix further impact protein fermentation and digestibility. Thus, in novel protein products without naturally occurring fiber, the health impact may differ from conventional plant protein sources. The influence of various fibers on plant-based protein metabolism throughout the gastrointestinal tract is not fully understood, necessitating further research.

Caffeic acid modulates intestinal microbiota, alleviates inflammatory response, and enhances barrier function in a piglet model challenged with lipopolysaccharide.

Young animals are highly susceptible to intestinal damage due to incomplete intestinal development, making them vulnerable to external stimuli. Weaning stress in piglets, for instance, disrupts the balance of intestinal microbiota and metabolism, triggering intestinal inflammation and resulting in gut damage. Caffeic acid (CA), a plant polyphenol, can potentially improve intestinal health. Here, we evaluated the effects of dietary CA on the intestinal barrier and microbiota using a lipopolysaccharide (LPS)-induced intestinal damage model. Eighteen piglets were divided into three groups: control group (CON), LPS group (LPS), and CA + LPS group (CAL). On the 21st and 28th day, six piglets in each group were administered either LPS (80 µg/kg body weight; Escherichia coli O55:B5) or saline. The results showed that dietary CA improved the intestinal morphology and barrier function, and alleviated the inflammatory response. Moreover, dietary CA also improved the diversity and composition of the intestinal microbiota by increasing Lactobacillus and Terrisporobacter while reducing Romboutsia. Furthermore, the LPS challenge resulted in a decreased abundance of 14 different bile acids and acetate, which were restored to normal levels by dietary CA. Lastly, correlation analysis further revealed the potential relationship between intestinal microbiota, metabolites, and barrier function. These findings suggest that dietary CA could enhance intestinal barrier function and positively influence intestinal microbiota and its metabolites to mitigate intestinal damage in piglets. Consuming foods rich in CA may effectively reduce the incidence of intestinal diseases and promote intestinal health in piglets.

Preventive effects of dietary fucoxanthin on ultraviolet A induced photoaging in hairless mice.

BACKGROUND: Repeated exposure to ultraviolet A (UVA) irradiation, which can penetrate the epidermis and reach the dermis, is one of the major causes of skin photoaging. Photoaged skin is characterized clinically by generalized wrinkling, a dry and loose appearance, and seborrheic keratoses, along with skin barrier dysfunction. Fucoxanthin, a xanthophyll carotenoid with a specific allenic bond and 5,6-monoepoxide in its structure, has been found to serve various functions as a food supplement. In the present study, the protective effects of orally administered fucoxanthin at relatively low concentrations (0.001% and 0.01%) against UVA induced photoaging were evaluated in vivo using hairless mice. RESULTS: Oral supplementation of 0.001% fucoxanthin was sufficient for its metabolites to accumulate in the skin, thereby inhibiting pathological changes induced by UVA irradiation, including impaired skin barrier function and accelerated wrinkle formation. Analysis of gene expression revealed that dietary fucoxanthin exerted antiphotoaging effects, possibly by modulating natural moisturizing factor (NMF) synthesis, desquamation, and ceramide composition in the epidermis, and by inhibiting the UVA induced degradation of collagen fibers and inflammation in the dermis. CONCLUSION: Taken together, our data indicate the potential application of dietary fucoxanthin as a novel ingredient in nutricosmetics for skin care against photoaging. © 2024 Society of Chemical Industry.

Clinical consequences of age-related skin barrier dysfunction. Part I. Structural, molecular and physiologic changes with cutaneous aging.

Aging is associated with significant changes to skin structure and function. As the United States population ages, dermatologists are increasingly presented with the clinical consequences of these changes. Understanding the biology of aging skin allows dermatologists to best guide patients towards proactive treatment of age-related skin disease. The first article of this 2-part continuing medical education series reviews the structural, molecular and functional changes associated with skin aging.

ß-Adrenoceptor Agonists Attenuate Thrombin-Induced Impairment of Human Lung Endothelial Cell Barrier Function and Protect the Lung Vascular Barrier during Resuscitation from Hemorrhagic Shock.

ß-adrenoceptor (ß-AR) agonists are known to antagonize thrombin-induced impairment (TII) of bovine and ovine lung endothelial barrier function. The effects of adrenoceptor agonists and other vasoactive agents on human lung microvascular endothelial cell (HULEC-5a) barrier function upon thrombin exposure have not been studied. Furthermore, it is unknown whether the in vitro effects of adrenoceptor agonists translate to lung protective effects in vivo. We observed that epinephrine, norepinephrine, and phenylephrine enhanced normal and prevented TII of HULEC-5a barrier function. Arginine vasopressin and angiotensin II were ineffective. α1B-, α2A/B-, and ß1/2-ARs were detectable in HULEC-5a by RT-PCR. Propranolol but not doxazosin blocked the effects of all adrenoceptor agonists. Phenylephrine stimulated ß2-AR-mediated Gαs activation with 13-fold lower potency than epinephrine. The EC50 to inhibit TII of HULEC-5a barrier function was 1.8 ± 1.9 nM for epinephrine and >100 nM for phenylephrine. After hemorrhagic shock and fluid resuscitation in rats, Evans blue extravasation into the lung increased threefold (p < 0.01 vs. sham). Single low-dose (1.8 µg/kg) epinephrine administration at the beginning of resuscitation had no effects on blood pressure and reduced Evans blue extravasation by 60% (p < 0.05 vs. vehicle). Our findings confirm the effects of ß-adrenoceptor agonists in HULEC-5a and suggest that low-dose ß-adrenoceptor agonist treatment protects lung vascular barrier function after traumatic hemorrhagic shock.

Chitosan-Stabilized Selenium Nanoparticles Alleviate High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) by Modulating the Gut Barrier Function and Microbiota.

Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs), a biologically active compound derived from selenium polysaccharides, have demonstrated potential in addressing obesity. However, the mechanism through which LCS-SeNPs alleviate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) remains unclear. Our results elucidated that LCS-SeNPs significantly inhibited fat accumulation and markedly improved the intestinal barrier by increasing mucus secretion from goblet cells. Moreover, LCS-SeNPs reshaped intestinal flora composition by increasing the abundance of mucus-associated microbiota (Bifidobacterium, Akkermansia, and Muribaculaceae_unclassified) and decreasing the abundance of obesity-contributed bacterium (Anaerotruncus, Lachnoclostridium, and Proteus). The modulation of intestinal microbiota by LCS-SeNPs influenced several metabolic pathways, including bile acid secretion, purine metabolites, and tryptophan derivation. Meanwhile, glycocholic acid and tauro-beta-muricholic acid were significantly reduced in the LCS-SeNP group. Our study suggests the crucial role of intestinal microbiota composition and metabolism, providing a new theoretical foundation for utilizing selenium polysaccharides in the intervention of HFD-induced NAFLD.

Ningxiang pig-derived Enterococcus hirae HNAU0516 ameliorates postweaning diarrhoea by promoting intestinal health and modulating the gut microbiota in piglets.

Early weaning-induced stress precipitates diarrhoea, significantly curtailing the growth performance of piglets. A pivotal contributor to this postweaning affliction is the emergence of gut bacterial dysbiosis. Enterococcus hirae, a promising probiotic, has indicated unclear effects and mechanisms on intestinal health. In this study, we investigated the effects and underlying mechanisms of oral supplementation with Ningxiang pig-derived Enterococcus hirae HNAU0516 orally supplementation on the gut bacterial community, immune response and gut barrier function in piglets. 21 d age Duroc × (Landrace × Yorkshire) piglets with a similar BW were randomly allocated to two groups. The Enterococcus hirae HNAU0516 administration group was inoculated orally with Ningxiang pig-derived Enterococcus hirae HNAU0516 throughout the trial period. Conversely, the control group received the same volume of physiological saline. Our findings revealed that Enterococcus hirae HNAU0516 supplementation effectively reduced diarrhoea rates of piglets (P = 0.010). Notably, this probiotic promoted intestinal development and enhanced intestinal barrier function. It also showed potential anti-inflammatory properties. Furthermore, Enterococcus hirae HNAU0516 supplementation significantly remodelled the colonic microbiota and increased the production of acetate (P = 0.007). In conclusion, our study highlights that Ningxiang pig-derived Enterococcus hirae HNAU0516 improves postweaning diarrhoea by promoting intestinal development, enhancing intestinal barrier function, decreasing intestinal permeability, modulating intestinal microbiota, and increasing short-chain fatty acids production.