Search Results (143)

This study aimed to investigate the effects of Pogostemon cablin essential oil (PEO) on rumen development in heat-stressed beef cattle. Eighteen male Jingjiang cattle were randomly assigned to two groups and fed a diet containing PEO at 0 mg/kg (Control) and 50 mg/kg in the feed concentrate (n = 9 per group). The rumen fluid samples had lower ammonia nitrogen and higher cellulase activity, propionate and total volatile fatty acids concentrations in the 50 mg/kg PEO group. Compared with the control group, 50 mg/kg dietary supplementation with PEO increased crude protein and neutral detergent fiber digestibility. Additionally, the ruminal tissue papilla height, the papilla surface area, and the activities of glutathione peroxidase, total superoxide dismutase, and total antioxidant capacity were also higher, while the malondialdehyde content was lower for the heat-stressed cattle in the 50 mg/kg PEO group. Furthermore, PEO increased the average optical density values and mRNA expression of zonula occludens-1 (ZO-1) and occludin (p < 0.05). Transcriptomics analysis of the rumen epithelium showed that PEO upregulated the expression levels of genes related to tight junction proteins and the DNA replication/repair pathways, while it downregulated pro-apoptotic genes. In summary, dietary PEO supplementation improved nutrient digestibility, enhanced rumen antioxidant capacity, and promoted the repair of damaged rumen epithelium in heat-stressed cattle, indicating that PEO exerts a prominent protective effect on rumen function. Full article

Background/Objective: Larazotide acetate (LA) is a synthetic octapeptide under development as a therapeutic candidate for celiac disease, acting to reduce intestinal permeability and regulate tight junctions (TJs). Although several studies have shown barrier-protective effects, the cellular mechanisms underlying LA’s actions in the intestinal epithelium remain unclear. This study aimed to elucidate the mechanistic roles of LA in maintaining intestinal epithelial integrity during cellular injury. Methods: C2BBe1 and leaky IPEC-J2 cell monolayers were pretreated with 10 mM LA and subjected to anoxia/reoxygenation (A/R) injury. Transepithelial electrical resistance (TEER), TJ protein localization, and phosphorylation of myosin light chain-2 (MLC-2) were analyzed. In addition, RNA sequencing was conducted to identify differentially expressed genes and signaling pathways affected by LA treatment. Results: LA pretreatment significantly increased TEER and preserved TJ protein organization during A/R injury. Transcriptomic analysis revealed enrichment of genes related to barrier regulation, small GTPase signaling, protein phosphorylation, proliferation, and migration. LA pretreatment markedly reduced MLC-2 phosphorylation, likely through modulation of the ROCK pathway, consistent with RNA-seq findings. Moreover, LA enhanced cellular proliferation, validating transcriptomic predictions. Conclusions: LA exerts a protective effect on intestinal epithelial integrity by stabilizing tight junctions, reducing MLC-2 phosphorylation, and promoting epithelial proliferation. These findings highlight a novel mechanism for LA and support its therapeutic potential in treating gastrointestinal disorders associated with “leaky gut” and mucosal injury. Full article

A limited supply and price shortages of fishmeal with the expansion of aquaculture make it necessary to seek alternative protein sources. Soybean meal (SM) has been the widely preferred replacer for fishmeal in fish diets. Nevertheless, this substitution, especially when given at high doses, potentially shows adverse impact on fish intestinal health. This study aimed to investigate the effect of replacing fishmeal with SM on intestinal health in olive flounder (Paralichthys olivaceus). A 56-day feeding trial was conducted with 450 juvenile fish (initial weight: 6.32 ± 0.01 g) randomly allocated to five diets with graded SM replacement: 0% (FM), 12% (SM12), 24% (SM24), 36% (SM36), and 48% (SM48). The results demonstrated that concentrations of glucose, total triglyceride, and low-density lipoprotein cholesterol increased, whereas total protein and high-density lipoprotein cholesterol contents, and lysozyme activity decreased in serum with increasing dietary SM levels. Meanwhile, total antioxidant capacity and superoxide dismutase activity significantly decreased at replacement levels exceeding 24%, accompanied by elevated malondialdehyde concentration (p < 0.05). Compared with the FM group, the SM24, SM36, and SM48 groups showed significantly reduced VH and increased lamina propria width (p < 0.05). Increasing dietary SM levels upregulated expression of genes related to endoplasmic reticulum stress (ERS) (chop, perk, and grp78), inflammation (tnf-α and il-6), and apoptosis (bax, casp3, casp6, and casp9), while downregulated anti-inflammatory cytokines (il-10 and tgf-β1) and tight junction-related genes (zo-1, zo-2, claudin-5, ocln, muc-13, and muc-15) in the intestine (p < 0.05). There were significant differences in the abundances of intestinal microbiota at both the phylum and genus levels among the FM, SM24, and SM36 groups (p < 0.05), but the clusters and microbiota composition of the SM24 group were more similar to those of the FM group. In conclusion, replacing 24% of fishmeal with SM induced intestinal dysfunction through evoking ERS, inflammation, barrier disruption, and microbial dysbiosis in olive flounder. Full article

Traumatic brain injury (TBI) disrupts the blood–brain barrier (BBB), resulting in increased permeability, neuronal loss, and cognitive dysfunction. This study investigates the therapeutic potential of thyroid hormone (T4) to reduce BBB dysfunction following moderate fluid percussion injury. T4 injection (intraperitoneal) after TBI restores the levels of pericytes and endothelial cells vital for BBB integrity, reduces edema by downregulating AQP-4 gene expression, and enhances levels of the tight junction protein ZO-1. T4 counteracts the TBI-related increase in MMP-9 and TLR-4, significantly reducing BBB permeability. Furthermore, T4 enhances the neuroprotective functions of astrocytes by promoting the activity of A2 astrocytes. Additionally, T4 treatment increases DHA levels (important for membrane integrity and function), stimulates mitochondrial biogenesis, and leads to a notable improvement in spatial learning and memory retention. These findings suggest that T4 has significant potential to reduce vascular leakage and inflammation after TBI, thereby improving cognitive function and maintaining BBB integrity. Full article

Type 2 diabetes mellitus (T2DM), a metabolic disorder defined by glucose and lipid metabolism dysregulation, has become a major global health issue. Hence, effective measures to prevent T2DM are urgently required. Lophatherum gracile Brongn (LGB) has been used in managing diabetes-related systemic diseases. However, the hypoglycemic bioactive components in LGB and the mechanisms underlying their hypoglycemic activity remain elusive. The current study sought to characterize the bioactive components of LGB and elucidate its mechanism of action against T2DM. Six common characteristic peaks were identified from six batches of LGB, with 39 characteristic chemical components preliminarily identified. Through component–activity correlation analysis, three functional components—namely isoorientin, orientin, and isovitexin—were selected as key candidates. In T2DM mice, LGB effectively improved glucose and lipid metabolic dysfunction. Untargeted metabolomics analysis revealed that LGB modulated pathways related to lipid and carbon metabolism. 16S rRNA gene sequencing and targeted metabolomics analysis revealed that LGB decreased the ratio of Firmicutes to Bacteroidetes and increased the abundance of bacterial groups such as Lactobacillales and Bacteroides. Additionally, LGB elevated the levels of SCFAs, specifically acetic and butyric acid. Moreover, LGB alleviated intestinal inflammation and upregulated the expression of tight junction proteins by inhibiting the LPS/TLR4/NF-κB signaling pathway. This study demonstrated that LGB treated T2DM, with isoorientin, orientin, and isovitexin identified as the main contributing components. The hypoglycemic mechanism is linked to the “gut microbiota−SCFAs−inflammatory response” signaling axis. Full article

Zonula occludens-1 (ZO-1), encoded by the TJP1 gene, is a crucial scaffolding protein within tight junctions that maintains epithelial and endothelial barrier integrity. In addition to its structural role, ZO-1 participates in signal transduction pathways that influence various cellular processes such as proliferation, differentiation, and apoptosis. Increasing evidence suggests that tight junction proteins, including ZO-1, play important regulatory roles in tumor progression, particularly by modulating metastasis, cell polarity, and vascular remodeling. Ovarian cancer, the most lethal gynecologic malignancy, is characterized by rapid growth, peritoneal dissemination, and a strong reliance on tumor angiogenesis. However, the specific role of ZO-1 in regulating angiogenesis within ovarian cancer remains poorly defined. In this study, we used CRISPR-Cas9-mediated gene editing to generate TJP1 knockout (KO) ovarian cancer cell lines and investigated the impact of ZO-1 loss on the expression of angiogenesis-related genes. Transcriptomic and qRT-PCR analyses revealed upregulation of KLF5 and IL-8, both of which are well-established pro-angiogenic factors. Furthermore, functional assessment using a Matrigel™ tube formation assay demonstrated that conditioned media from ZO-1-deficient cells significantly enhanced endothelial tube formation. These findings indicate that ZO-1 loss promotes a pro-angiogenic tumor microenvironment, likely through modulation of key signaling molecules such as KLF5 and IL-8. Therefore, ZO-1 may serve as a potential suppressor of angiogenesis and a therapeutic target in ovarian cancer. Full article

Goats are important producers of meat, milk, hair, and leather. Early-weaned kids may encounter issues such as weaning stress and stress from high-density farming, which can hinder their growth and development. Therefore, exploring feed additives capable of alleviating stress in kids to enhance their growth performance is of particular importance. This experiment aims to investigate the effects of inulin on the growth performance, immune function, and intestinal health of weaned kids. Thirty healthy 60-day-old Leizhou black goat weaned kids with similar body weights (9.00 ± 0.05 kg) were selected and evenly divided into five groups by weight, with six kids in each group. The control group was fed the basal diet, while the AM HCl group received 0.05‰ aureomycin hydrochloride. The inulin groups were supplemented with 0.1%, 0.3%, and 0.5% inulin, respectively. By comparison, the results of the 0.3% inulin group in this experiment were most consistent with those of the AM HCl group, and the final weight of the kids was the highest. The 0.3% and 0.5% inulin groups had significantly enhanced immune-related indicator (such as sIgA, IgA, and IgG) concentrations and antioxidant activities (p < 0.05) in kids. Inulin significantly increased cecal total volatile fatty acids (TVFA) and the activities of jejunal α-amylase, chymotrypsin, and trypsin (p < 0.05); the activities of intestinal antioxidant enzymes, including GSH-PX, SOD, and T-AOC, were significantly increased (p < 0.05); and the intestinal anti-inflammatory factor IL-10 was significantly elevated (p < 0.05). Inulin significantly increased the mRNA expression levels of the tight junction protein genes TJP1 (ZO-1) and OCLN in the jejunum (p < 0.05). It also significantly upregulated the mRNA expression levels of anti-inflammatory factors TGF-β1 and IL-10 while significantly reducing the mRNA level of pro-inflammatory factor IL-6 in the jejunum (p < 0.05). Therefore, inulin enhanced the growth performance and antioxidant capacity of weaned kids, improved the body’s immune response, and reduced inflammatory responses. Specifically, when comparing the growth status, antioxidant enzyme activity, and tight junction protein mRNA level among the groups of kids, the 0.3% inulin supplementation yielded the best results in this experiment. Full article

Citrinin (CTN), a mycotoxin commonly found in contaminated food and animal feed, impairs intestinal barrier integrity through oxidative stress and cytotoxicity. However, its link to ferroptosis, an iron-dependent form of regulated cell death, remains unclear. This study investigated whether CTN induces ferroptosis in intestinal epithelial cells and evaluated the protective role of Euphorbia hypericifolia (EH) against CTN-induced oxidative damage and tight junction (TJ) disruption. Using IPEC-J2 cells exposed to CTN, intracellular ferrous ion (Fe²⁺) levels, reactive oxygen species (ROS) accumulation, and TJ integrity were assessed using FerroOrange and DCFH-DA staining, RT-qPCR, immunofluorescence, and WST-1 assays. Additionally, a high-throughput screen of 459 natural products identified EH extract as a top candidate in mitigating CTN toxicity. The CTN treatment significantly elevated intracellular Fe²⁺ and ROS levels, downregulated antioxidant genes (notably CAT), and disrupted ZO-1 expression and TJ morphology in IPEC-J2 cells, all hallmarks of ferroptosis-like cell death. Co-treatment with EH extract effectively reversed these effects, restoring antioxidant gene expression, reducing Fe²⁺ and ROS accumulation, and preserving TJ structure. Phytochemical profiling of EH extract revealed several bioactive compounds potentially responsible for its protective effects. These findings suggest that CTN induces ferroptosis-related cytotoxicity in IPEC-J2 cells, but EH alleviates this toxicity by modulating oxidative stress and iron homeostasis, supporting its potential use as a natural feed additive for intestinal protection Full article

Background: Clostridium perfringens (C. perfringens) type A is a major cause of enteritis in farmed and wild deer populations, leading to significant economic losses in the deer industry. This bacterium produces toxins that damage the intestine. Methods: In this study, we performed transcriptome analysis by establishing an intestinal circulation model of the intestines of fallow deer (Dama Dama) inoculated with C. perfringens type A versus those not inoculated with C. perfringens type A. In a further step, we determined the protein content of immunoinflammation-related molecules by ELISA and the antioxidant capacity of the intestine to investigate the molecular mechanisms of C. perfringens type A-induced enteritis. Results: Transcriptome analysis revealed significant enrichment of pathways related to the haematopoietic system, oxidative stress, the immune system and intestinal tight junctions. Additionally, C. perfringens α-toxin enters the intestine and may be recognized by TLR6, activating the immune system, increasing the secretion of various cytokines and inflammasome components, inducing oxidative stress and damaging the intestine. Conclusions: This study provides a comprehensive transcriptomic basis for understanding the selective differential expression of genes in deer enteritis induced by C. perfringens type A and provides a broader guide for finding therapeutic approaches to deer enteritis. Full article

Early-life brain injuries are major causes of long-term neurodevelopmental disorders such as cerebral palsy. Emerging evidence suggests these injuries can alter the gut microbiota composition, intestinal integrity, and neuroinflammatory responses. This systematic review evaluated the impact of early-life brain injuries on the gut microbiota in rodent models. A scientific literature search was conducted across Medline/PubMed, Web of Science, Scopus, and Embase. Initially, 7419 records were identified, and 21 eligible studies were included. Eligible studies focused on evaluating the microbiota alterations and related gut–brain axis markers at the neonatal or post-weaning stages. The data extraction and synthesis followed PRISMA guidelines. Most studies reported gut dysbiosis characterized by a decreased abundance of Bacteroidetes, and Lactobacillus. Alterations were associated with an increased gut permeability, reduced tight junction proteins, and elevated pro-inflammatory cytokines. Several studies showed reduced levels of short-chain fatty acids and metabolic pathway disruptions. Brain outcomes included neuroinflammation, white matter injury, altered gene expression, and impaired structural integrity. These results suggest that early-life brain injury induces complex alterations in the gut microbiota and its metabolic products, which may contribute to systemic and neuroinflammatory processes. Understanding these interactions offers insights into the pathophysiology of neurodevelopmental disorders and highlights the gut–brain axis as a potential target for early interventions. Full article

This study aimed to evaluate the effects of dietary supplementation with sodium butyrate (SB) in different forms on the growth performance, antioxidant capacity, immune response, and intestinal health of largemouth bass (Micropterus salmoides). Five diets were formulated: a basal diet (SB0), diets with 1000 (ESB1), 1500 (ESB2), and 2000 mg/kg encapsulated SB (ESB3), and a diet with 2000 mg/kg raw powder sodium butyrate (RSB, non-encapsulated). After 49 days of feeding trials, the ESB2 group exhibited significantly higher weight gain and specific growth rates and a lower feed coefficient than those of the SB0 group (p < 0.05). Compared with the SB0 group, proximal intestinal villus length and width were significantly increased in the ESB1, ESB2, and ESB3 groups (p < 0.05). The expressions of tight junction genes zo-1, claudin-1, and claudin-4 were up-regulated in these SB-supplemented groups and most pronounced in the ESB2 group (p < 0.05). Compared with the SB0 group, antioxidant enzyme activities (catalase and superoxide dismutase) and their gene expressions increased in the ESB1, ESB2, and RSB groups (p < 0.05). Immune-related genes il-10 and tgf-β1 were up-regulated in the ESB1 and ESB2 groups, while their il-8, il-1β, and tnf-α were down-regulated (p < 0.05). The ESB2 group had higher intestinal abundance of Firmicutes and Lactobacillus. In conclusion, dietary supplementation with 1500 mg/kg encapsulated SB (ESB2) improved growth, antioxidant capacity, immunity, and gut health in largemouth bass. Full article

Chickpeas are used as alternative protein sources in healthy snacks due to their bioactive compounds beneficial for gut health. Combining chickpeas with dark chocolate improves palatability and may enhance biological functionality, although mechanistic evidence is still limited. In this explorative research, we evaluate the nutrigenomic, antioxidant and anti-inflammatory properties of a chickpea and chocolate snack using in vitro Caco-2 (colon adenocarcinoma cells) and THP-1 (monocyte-derived macrophages) models. The total polyphenol content and antioxidant activity were measured after in vitro digestion (30.30 mg/mL to 1.9 mg/mL). Caco-2 epithelia and THP-1 were pre-treated for 4 days (2 h/day) with high (15.1 mg/mL) or low (3.8 mg/mL) concentrations of digests. Inflammation was induced for 3 h by LPS (Lipopolysaccharides) and IL-1β (Interleukin-1β). Transepithelial electrical resistance (TEER) was measured to assess barrier integrity. Gene expression related to tight junctions and inflammation was analysed using qPCR (quantitative polymerase chain reaction). Chocolate and snack digests showed the highest total polyphenol content and 2,2-diphenyl-1-picrylhydrazyl activity. Barrier integrity improved with all treatments. Chickpea upregulated tight junction gene expression. Chickpea and chocolate reduced IL-1β expression in both cell types. In THP-1, the chocolate and the snack upregulated CD206 (mannose receptor C-type 1) expression. IL-10 increased with all treatments. These results pave the way for future research that may support the potential use of this snack as a functional food with antioxidant, gut-protective and anti-inflammatory effects. Full article

Objectives: In this study, we investigated the effects of intravenous glutamine (GLN) administration on the Toll-like receptor 3 (TLR3) antiviral pathway and leukocyte migration in mice with poly(I:C)-induced acute lung injury (ALI). Methods: There were four groups in this study: the NC group, mice without an intratracheal injection; the SH group, mice intratracheally injected with endotoxin-free saline; the PS group, intratracheally instilled with 3 mg poly(I:C)/kg body weight (BW), followed by an intravenous (IV) injection of saline; and the PG group, intratracheally injected with poly(I:C) followed by the IV administration of 0.75 g GLN/kg BW. Mice in the SH, PS, and PG groups were sacrificed at 4, 12, and 24 h after intratracheal instillation. Results: The results showed that poly(I:C) stimulation decreased the plasma GLN concentration and increased inflammatory cytokine levels. In bronchoalveolar lavage fluid, concentrations of interferon λ3 and percentages of macrophages and M1 macrophages decreased, while neutrophils increased along with significantly elevated myeloperoxidase activity in lung tissues. The gene expressions of molecules related to leukocyte migration increased, whereas tight/adherens junction expressions in endothelial and epithelial cells were reduced. GLN supplementation upregulated the mRNA and/or protein expressions of TLR3 antiviral pathway-related factors and tight/adherens junctions while reducing inflammatory cytokines and the expressions of leukocyte migration molecules. Histological results also showed that lung injury was attenuated. Conclusions: These findings indicated that intravenous GLN administration after poly(I:C) instillation restored plasma GLN levels and alleviated ALI by activating the TLR3 antiviral pathway, suppressing leukocyte migration and neutrophil infiltration, mitigating inflammation, and improving the integrity of the alveolar–capillary barrier. Full article

Sleep deprivation is a prevalent issue that disrupts the circadian rhythm of estrogen, particularly estradiol, thereby significantly affecting women’s skin health and appearance. These disruptions can impair skin barrier functionality and decrease dermal collagen synthesis. In this study, our results demonstrate that topical taurine supplementation promotes the expression of tight junction (TJ)-related proteins and enhances collagen production, effectively restoring skin homeostasis in sleep-deprived female mice. Mechanistically, taurine upregulates the expression of TMEM38B, a gene encoding the TRIC-B trimeric cation channel, resulting in increased intracellular calcium ion levels. This, in turn, promotes the upregulation of TJ-related proteins, such as ZO-1, occludin, and claudin-11 in epidermal cells, while also enhancing the expression of type III collagen in fibroblasts, thus restoring skin homeostasis. These findings suggest that taurine may serve as an alternative to estradiol, effectively improving skin homeostasis disrupted by sleep deprivation while mitigating the potential risks associated with exogenous estrogen supplementation. Collectively, these results provide preliminary insights into the protective mechanisms of taurine against sleep deprivation-induced skin impairments and establish a foundation for its potential application in treating skin conditions related to estrogen imbalances, such as skin aging in menopausal women. Full article

The objective of this study was to determine whether hydroxy-selenomethionine (OH-SeMet) exerts better protective effects on sows against heat stress than sodium selenite (SeNa) or seleno-yeast (SeY). A total of 60 sows (Landrace × Yorkshire) were randomly allocated into the three groups and fed a base diet supplemented with SeNa, SeY, or OH-SeMet at 0.3 mg Se/kg under a heat stress condition for a reproductive cycle. Compared to SeNa or SeY, OH-SeMet could more effectively sustain offspring growth performance, as evidenced by an increased number of live-born piglets, higher litter weight at day 21, and greater litter body weight gain from days 1 to 21. OH-SeMet was more effective in supporting endogenous redox systems, as shown by enhanced levels of TXNRD and GSH and reduced levels of GSSG in the serum of sows, improved T-AOC, TXNRD, and GSH alongside decreased MDA and GSSG in the serum of piglets, and heightened T-AOC in the jejunum of piglets. Furthermore, among the two tested organic Se sources, OH-SeMet was more effective than SeY in regulating immune responses compared to SeNa. OH-SeMet reduced inflammation-related markers CRP, HP, MAP, LPS, IL-1β, IL-6, and TNF-α, some or all of which were reduced in the serum of sows and their offspring. In addition, OH-SeMet also showed reduced glucose, TG, and NEFA levels, along with elevated insulin levels in the serum of sows. Correspondingly, among the two organic forms of Se, particularly those sows fed OH-SeMet showed better gut protection for the sows’ offspring, as indicated by a reduced crypt depth and increased villus height/crypt depth ratio in the duodenum, jejunum, and ileum than those fed SeNa. Specifically, compared to SeNa or SeY, OH-SeMet upregulated the expression of selenoproteins (GPX6, TXNRD3, GPX4, and SELENON), the tight junction protein (ZO-1), and host defense peptide gene (pBD1, pBD2, pBD3, NPG3, NPG4), along with downregulating levels of inflammation factor (IL-1β, IL-6 and TNF-α) and pro-apoptotic factor (P53) in the jejunum of piglets. Taken together, OH-SeMet more effectively mitigated the adverse effects induced by heat stress in sows and their offspring. Full article