Search Results (303)

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Intestinal inflammation involves barrier impairment, immune hyperactivation, and oxidative stress imbalance. Bioactive polysaccharides universally alleviate inflammation via anti-inflammatory, antioxidant, and microbiota-modulating effects, yet exhibit distinct core mechanisms. Elucidating these differences is vital for targeted polysaccharide applications. This research examines distinct regulatory pathways through which diverse bioactive polysaccharides mitigate lipopolysaccharide-triggered intestinal inflammation in male Kunming (KM) mice. This experiment employed Lentinula edodes polysaccharide (LNT), Auricularia auricula polysaccharide (AAP), Cordyceps militaris polysaccharide (CMP), Lycium barbarum polysaccharide (LBP), and Brassica rapa polysaccharide (BRP). The expression levels of biomarkers associated with the TLR4 signaling pathway, oxidative stress, and intestinal barrier function were quantified, along with comprehensive gut microbiota profiling. The results showed that all five polysaccharides alleviated inflammatory responses in mice by inhibiting inflammatory cytokine release, reducing oxidative damage, and modulating gut microbiota, but their modes of action differed: LBP significantly suppressed the TLR-4/MyD88 signaling pathway and its downstream pro-inflammatory cytokine expression, thereby blocking inflammatory signal transduction and reducing oxidative damage; LNT and CMP enhanced the body’s antioxidant capacity by increasing antioxidant enzyme activities and decreasing malondialdehyde (MDA) levels; AAP and BRP enriched Akkermansia (Akk.) within the Verrucomicrobia (Ver.) phylum, upregulating tight junction protein expression to strengthen the intestinal mucosal barrier and indirectly reduce oxidative damage. This research demonstrates that different polysaccharides alleviate inflammation through multi-target synergistic mechanisms: LBP primarily inhibits inflammatory pathways; AAP and BRP focus on intestinal barrier protection and microbiota modulation; and LNT and CMP exert effects via antioxidant enzyme activation. These data support designing polysaccharide blends that leverage complementary inflammatory modulation mechanisms. Full article

Major Depressive Disorder (MDD) is increasingly linked to disruptions in blood-brain barrier (BBB) integrity, contributing to neuroinflammation and impaired brain homeostasis. While traditional antidepressant therapies often fail to achieve full remission, growing evidence suggests that specific dietary compounds may offer novel avenues for restoring BBB function and improving mental health outcomes. This review explores the potential of selected nutrients—omega-3 fatty acids, vitamin D, sulforaphane, fucoidan, and urolithins—to modulate BBB integrity through anti-inflammatory, antioxidant, and transporter-regulatory mechanisms. These compounds act by reinforcing tight junctions, reducing matrix metalloproteinase activity, and modulating efflux transporters such as P-glycoprotein. Although current evidence is largely preclinical, the mechanistic insights provided in this review support the rationale for integrating nutritional strategies into the management of MDD. Future clinical studies are needed to validate these findings and develop biomarker-driven approaches for targeting the BBB in nutritional interventions for psychiatric disorders. Full article

Glioblastoma is the most common and aggressive malignant primary brain tumour. Patients with glioblastoma have a median survival of only around 14.6 months after diagnosis, despite the availability of various conventional multimodal treatments including chemotherapy, radiation therapy, and surgery. Therefore, photodynamic therapy (PDT) has emerged as an advanced, selective and more controlled therapeutic approach, which has minimal systemic toxicity and fewer side effects. PDT is a less invasive therapy that targets all cells or tissues that possess the photosensitizer (PS) itself, without affecting the surrounding healthy tissues. Polymeric NPs (PNPs) as carriers can improve the targeting ability and stability of PSs and co-deliver various anticancer agents to achieve combined cancer therapy. Because of their versatile tuneable features, these PNPs have the capacity to open tight junctions of the blood–brain barrier (BBB), easily transport drugs across the BBB, protect against enzymatic degradation, prolong the systemic circulation, and sustainably release the drug. Conjugated polymer NPs, poly(lactic-co-glycolic acid)-based NPs, lipid–polymer hybrid NPs, and polyethylene-glycolated PNPs have demonstrated great potential in PDT owing to their unique biocompatibility and optical properties. Although the combination of PDT and PNPs has great potential and can provide several benefits over conventional cancer therapies, there are several limitations that are hindering its translation into clinical use. This review aims to summarize the recent advances in the combined use of PNPs and PDT in the case of glioblastoma treatment. By evaluating various types of PDT and PNPs, this review emphasizes how these innovative approaches can play an important role in overcoming glioblastoma-associated critical challenges, including BBB and tumour heterogeneity. Furthermore, this review also discusses the challenges and future directions for PNPs and PDT, which provides insight into the potential solutions to various problems that are hindering their clinical translation in glioblastoma treatment. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by immune dysregulation, microbiota imbalance, and intestinal barrier dysfunction. Despite its global burden, effective therapies remain limited. This study explores the therapeutic potential of Agrocybe cylindracea polysaccharides (ACP) in a dextran sulfate sodium (DSS)-induced murine colitis model. High-performance liquid chromatography (HPLC)-characterized ACP was administered orally to BALB/c mice following colitis induction. ACP treatment significantly reduced Disease Activity Index (DAI) scores, preserved colon length, and restored intestinal barrier integrity by upregulating tight junction proteins. Mechanistically, ACP modulated immune homeostasis, suppressing pro-inflammatory cytokines (IL-17, IL-23, CRP) while enhancing anti-inflammatory mediators (IL-4, TGF-β). Furthermore, ACP inhibited hepatic TLR4/MyD88/NF-κB signaling, attenuated systemic inflammation, and reshaped gut microbiota composition by enriching beneficial taxa and reducing pathogenic Bacteroides. These findings demonstrate ACP multi-target efficacy in colitis, positioning it as a promising natural therapeutic for UC. Full article

Sarcopenia, the age-related loss of skeletal muscle mass and function, is associated with inflammation, mitochondrial dysfunction, and gut barrier impairment. This study investigates the postbiotic effects of heat-killed Lactiplantibacillus plantarum HY7715 (HY7715) and its extracellular vesicles (EVs) on muscle health and intestinal integrity. In C2C12 myotubes, both treatments enhanced myogenic differentiation by upregulating Myf5 and MYOG, and improved mitochondrial activity and biogenesis via increased PGC1α and mTOR expression. Under TNFα-induced muscle atrophy, they suppressed expression of atrophy-related markers (Fbox32, MuRF1, and myostatin). EVs showed stronger anti-inflammatory effects by reducing IL6 expression in muscle cells. In intestinal Caco-2 cells, HY7715-derived EVs improved barrier function by upregulating tight junction proteins (ZO-1, occludin, and claudins), and effectively reduced LPS-induced inflammation. These findings suggest that heat-killed HY7715 and its EVs may alleviate sarcopenia by enhancing muscle regeneration and maintaining intestinal homeostasis, highlighting their potential as safe, gut–muscle axis-targeting postbiotic interventions for healthy aging. 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

Rosacea is a chronic inflammatory skin condition characterized by persistent erythema and telangiectasia, often accompanied by skin barrier disruption and abnormal angiogenesis. Currently, peptide-based therapies for rosacea are limited, and existing drugs still present certain limitations and side effects. Peptides have the advantage of being relatively safe and exhibiting high target specificity, which can reduce the risk of adverse effects. Considering these points, this study aimed to explore the adhesive peptide AdhPep3 (AYDPGYK) as a potential therapeutic candidate for rosacea. AdhPep3 was designed based on protein sequences with cell junction properties and has the potential to enhance skin barrier-related protein expression by improving cell–cell adhesion and increasing adhesion-related protein levels. In LL-37-stimulated HaCaT cells, AdhPep3 effectively alleviated skin inflammation and inhibited the Toll-like receptor–nuclear factor kappa B (TLR2–NFκB) signaling pathway. Additionally, in LL-37-stimulated human umbilical vein endothelial cells (HUVECs), it reduced cell migration and the expression of angiogenesis-related proteins. Since AdhPep3 demonstrated anti-inflammatory and anti-angiogenic effects at the in vitro level, it may serve as a potential therapeutic agent for rosacea. Moreover, by increasing the expression of skin barrier and tight junction-related proteins, AdhPep3 shows potential for development as a cosmetic ingredient to improve skin health. Full article

Background: Vitamin D is increasingly recognized not only for its role in skeletal development but also for its immunomodulatory and gastrointestinal effects. Maternal and neonatal vitamin D deficiency (VDD) has been associated with alterations in gut microbiota, impaired intestinal barrier integrity, and increased susceptibility to inflammatory conditions in neonates. However, the exact mechanisms linking perinatal vitamin D status to neonatal gastrointestinal morbidity remain incompletely understood. Methods: This review synthesizes current evidence (2015–2024) from clinical studies, animal models, and mechanistic research on the impact of VDD during pregnancy and the neonatal period on gastrointestinal health. Databases such as PubMed, Scopus, and Web of Science were systematically searched using keywords, including “vitamin D”, “neonate”, “gut microbiome”, “intestinal barrier”, and “necrotizing enterocolitis”. Results: Emerging data suggest that VDD in utero and postnatally correlates with dysbiosis, increased intestinal permeability, and elevated inflammatory responses in neonates. Notably, low 25(OH)D levels in mothers and newborns have been linked with a higher incidence of necrotizing enterocolitis (NEC), delayed gut maturation, and altered mucosal immunity. Vitamin D appears to modulate the expression of tight junction proteins, regulate antimicrobial peptides, and maintain microbial diversity through the vitamin D receptor (VDR). Conclusions: Understanding the gastrointestinal implications of early-life VDD opens a potential window for preventive strategies in neonatal care. Timely maternal supplementation and targeted neonatal interventions may mitigate gut-related morbidities and improve early-life health outcomes. Further longitudinal and interventional studies are warranted to clarify causality and optimal intervention timing. Full article

Background/Objectives: Gypenosides (Gps) are the main active compounds of Gynostemma and show promise in managing diabetes; nevertheless, the mechanism by which Gps exert anti-diabetic effects is still not fully understood. The aim of this study is to clarify the molecular mechanisms of Gps in ameliorating glucose dysregulation. Methods: Qualitative and quantitative analyses on the chemical components of Gps were performed, respectively. Type 2 diabetes mellitus mouse models were established, and the mice were subsequently treated with Gps at doses of 200, 100, or 50 mg/kg for 4 weeks. Biochemical markers were measured. Histopathological assessments of hepatic and colonic tissues were conducted. The compositions of the intestinal microbiota, short-chain fatty acids (SCFAs), and bile acids (BAs) in fecal samples were analyzed. Western blotting was applied to examine the activation of relevant signaling pathways. Results: Gps have potent regulatory effects on metabolic homeostasis by improving glucose and lipid profiles and alleviating hepatic tissue damage. Treatment with Gps significantly reduced serum levels of lipopolysaccharides and key pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Moreover, Gps enhanced the integrity of the gut barrier by upregulating the level of tight junction proteins (ZO-1 and occludin). Microbiota profiling revealed that Gps markedly increased microbial diversity and richness, decreased the ratio of Firmicutes/Bacteroidetes, and elevated Bacteroidia abundance from the phylum to the genus level. Targeted metabolomics further demonstrated that Gps modulated gut microbial metabolites by promoting SCFA production and reshaping BA profiles. Specifically, Gps elevated the primary-to-secondary BA ratio while reducing the 12α-hydroxylated to non-12α-hydroxylated BA ratio. Mechanistically, Western blotting demonstrated that Gps triggered the hepatic PI3K/AKT pathway and the intestinal BA/FXR/FGF15 axis, suggesting the coordinated regulation of metabolic and gut–liver axis signaling pathways. Conclusions: Gps significantly ameliorate hyperglycemia and hyperlipidemia through a multifaceted mechanism involving gut microbiota modulation, the restoration of intestinal barrier function, and the regulation of microbial metabolites such as SCFAs and BAs. These findings offer novel insights into their mechanism of action via the gut–liver axis. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), driven by obesity and metabolic syndrome, is increasingly prevalent and a significant contributor to liver fibrosis, cirrhosis, and liver-related mortality. Emerging research implicates the gut microbiome as a critical player in MASLD progression, yet specific microbial drivers remain poorly understood. Here, we explore the role of Prevotella copri (P. copri) in MASLD progression through both human patient cohorts and a mouse model of diet-induced obesity. Methods/Results: Using 16S rRNA sequencing, we identified elevated P. copri abundance in MASLD patients with advanced fibrosis, linked with significant shifts in microbial diversity and bacterial network connectivity. To investigate causality, experimental colonization of P. copri in mice on a high-fat diet worsened MASLD progression, with P. copri-colonized mice showing significant increases in hepatic steatosis, liver triglyceride accumulation, and body weight, independent of caloric intake. At the molecular level, P. copri colonization downregulated key lipid metabolism genes, such as carnitine palmitoyltransferase 1 and adipose triglyceride lipase, and impaired tight intestinal junction integrity through the downregulation of occludin. Collectively, our findings position P. copri as a possible driver of MASLD progression by promoting hepatic steatosis through lipid and triglyceride accumulation and fibrosis through decreased tight junction integrity. These insights suggest a promising therapeutic avenue to target specific microbial signatures like P. copri to curb MASLD progression and mitigate the associated risk of advanced fibrosis. Full article

Background/Objectives: Gastric cancer (GC) is the fifth leading cause of cancer-related mortality. CLDN18.2 is a tight junction protein, expressed in gastric mucosa and is considered as a novel therapeutic target. Even though CLDN18.2 is associated with various components of the tumor microenvironment and the relation with clinical histopathological parameters has been widely studied, there is no sufficient data on the associations of CLDN18.2 expression and the components of the tumor microenvironment. This systematic review aims to gather and present all available data about the correlation of CLDN 18.2 expression and the tumor microenvironment. Methods: The research questions were systematically formulated using the PICO model to ensure clarity and precision, and the PRISMA flow diagram was constructed to detail the study selection process. Results: Sixteen original articles were retrieved. The major finding of this study was the positive correlation between CLDN18.2 expression and CD8+ T cells, neutrophils and cancer-associated fibroblasts. No correlation was found between CLDN18.2 expression and Tregs and B cells. For the remaining components of the microenvironment, there are contradictory data about their correlation with the expression of CLDN18.2. Conclusions: The tumor microenvironment plays a critical role in cancer progression and needs to be studied more thoroughly. Full article

The gut serves as the main site for nutrient digestion and absorption. Simultaneously, it functions as the body’s largest immune organ, playing a dual role in sustaining physiological equilibrium and offering immunological defense against intestinal ailments. Maintaining the structural and functional integrity of the intestine is paramount for ensuring animal health and productivity. Puerarin, a naturally derived isoflavonoid from the Pueraria species, exhibits multifaceted bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Emerging evidence highlights puerarin’s capacity to enhance gut health in farm animals through four pivotal mechanisms: (1) optimization of intestinal morphology via crypt-villus architecture remodeling, (2) augmentation of systemic and mucosal antioxidant defenses through Nrf2/ARE pathway activation, and (3) reinforcement of intestinal barrier function by regulating tight junction proteins (e.g., ZO-1, occludin), mucin secretion, intestinal mucosal immune barrier, the composition of microbiota, and the derived beneficial metabolites; (4) regulating the function of the intestinal nervous system via reshaping the distribution of intestinal neurons and neurotransmitter secretion function. This review synthesizes current knowledge on puerarin’s protective effects on intestinal physiology in farm animals, systematically elucidates its underlying molecular targets (including TLR4/NF-κB, MAPK, and PI3K/Akt signaling pathways), and critically evaluates its translational potential in mitigating enteric disorders such as post-weaning diarrhea and inflammatory bowel disease in agricultural practices. Full article

Probiotics are widely used as dietary additives to strengthen gut barrier function, shape microbiota composition, regulate host metabolism, and promote overall health. To enhance probiotic delivery and microbial viability, this study evaluated a liquid feeding system supplemented with a probiotic consortium (Bifidobacterium infantis, Lactobacillus plantarum, and Pediococcus acidilactici) in nursery piglets. A 60-day trial involving 270 piglets (16.84 ± 0.12 kg) compared three diets: solid feed (Dry), liquid feed (Liq), and probiotic-enriched liquid feed (Pro). Compared to the Dry and Liq groups, probiotic supplementation significantly improved growth performance, with the average daily gain increasing by over 17.86% (p < 0.01) and the average daily feed intake increasing by more than 6.08% (p < 0.05). The feed conversion ratio was reduced by up to 8.08% (p < 0.05), indicating improved feed efficiency. The Pro group also exhibited elevated tight junction protein expression (p < 0.05), increased colonic short-chain fatty acid levels (p < 0.01), and decreased serum biomarkers of intestinal permeability (p < 0.05). The 16 S rRNA sequencing indicated the probiotic-driven colonization of B. infantis and L. plantarum and the suppression of opportunistic pathogens. Metabolomic analyses revealed enhanced colonic tryptophan metabolism, evidenced by elevated kynurenic and xanthurenic acid levels. Additionally, serum-targeted metabolomics and in vitro experiments confirmed that B. infantis and L. plantarum effectively converted tryptophan into indole-3-lactic acid, promoting its accumulation in piglet serum and colons. These results deepen our understanding of the mechanisms by which probiotics and tryptophan metabolism enhance intestinal health, providing a foundational platform for the application of probiotic-based interventions in livestock production. Full article

Background: The blood–brain barrier (BBB) plays a critical role in protecting the central nervous system (CNS) but also limits drug delivery. Insufficient knowledge of how the CNS promotes the onset and maintenance of peripheral neuropathic pain limits therapeutic methods for the treatment of persistent neuropathic pain. Thus, this study aimed to evaluate the ability of a novel combination of Palmitoylethanolamide (PEA) and Equisetum arvense L. (Equisetum A.L.) to cross the BBB and modulate nociceptive pathways. Methods: Using a humanised in vitro BBB tri-culture model, the permeability, cytotoxicity, and integrity of the barrier were assessed after exposure to two different PEA forms, PEA ultramicronized (PEA-um) and PEA80mesh, Equisetum A.L., and a combination of the last two samples. The samples exhibited no cytotoxicity, maintained tight junction integrity, and efficiently crossed the blood–brain barrier (BBB), with the combination displaying the highest permeability. The eluate from the BBB model was then used to stimulate the co-culture of CCF-STTG1 astrocytes and SH-SY5Y neurons pre-treated with H₂O₂ 200 µM. Results: Treatment with the combination significantly increased cell viability (1.8-fold, p < 0.05), reduced oxidative stress (2.5-fold, p < 0.05), and decreased pro-inflammatory cytokines (TNFα, IL-1β) compared to single agents. Mechanistic analysis revealed modulation of key targets involved in pain pathways, including decreased FAAH and NAAA activity, increased levels of endocannabinoids (AEA and 2-AG), upregulation of CB2 receptor expression, enhanced PPARα activity, and reduced phosphorylation of PKA and TRPV1. Conclusions: These findings suggest that the combination of PEA and Equisetum A.L. effectively crosses the BBB and exerts combined anti-inflammatory and analgesic effects at the CNS level, suggesting a possible role in modulating neuroinflammatory and nociception responses. Full article