Cyclosporine A ameliorates ulcerative colitis by inhibiting cellular senescence, modulating the JAK2-STAT3/NF-κB signaling pathway, and regulating the gut microbiota-metabolite axis.

Thrombospondin-1-mediated macrophage efferocytosis dysfunction exacerbates intestinal pathology in Hirschsprung's disease.

Bioprinted dressing with symbiotic microbes for oxygen supply and antibacterial therapy for enhanced diabetic wound healing.

Thermosensitive porcine acellular dermal matrix hydrogel loaded with umbilical cord mesenchymal stem cell-derived exosomes for diabetic wound healing repair.

Dextran-based microneedle patch Co-delivering safflower polysaccharide and ROS-responsive tetramethylpyrazine micelles for diabetic wound repair.

Comparative analysis of key phagocytic genes in humans and mice using machine learning integrated with single-cell RNA sequencing.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by persistent synovial inflammation, pathological angiogenesis, and progressive joint destruction. Emerging evidence implicates the renin-angiotensin system (RAS) and neuropilin-1 (NRP-1) as key modulators of RA pathogenesis through regulation of inflammatory signaling, vascular remodeling, and osteoclastogenesis. This study explored the mechanistic interplay between RAS and NRP-1 signaling in a rat model of RA induced by complete Freund's adjuvant. Experimental groups received valsartan (VAL), an angiotensin II type-1 receptor (AT-1R) antagonist; ramipril (RAM), an ACE inhibitor or methotrexate (MTX), the standard anti-rheumatic agent. NRP-1 ligand-binding (VEGF-165/Sema3A) and dimerization-associated domain expression were evaluated via immunohistochemistry and western blot. Transcriptional expression of VEGF-165, Sema3A was quantified using qRT-PCR, while RhoA, p-ERK protein levels were assessed by ELISA. Systemic inflammatory mediators (anti-CCP, TNF-α, IL-1β) and the bone resorption marker RANKL were also determined. Histopathological and scanning electron microscopy (SEM) analyses with morphometric evaluation assessed joint integrity. Both VAL and RAM significantly modulated NRP-1 signaling, influencing ligand-receptor interactions, dimerization, and downstream mediators (RhoA, p-ERK). These effects were accompanied by reduced inflammatory activity and preservation of bone and cartilage structure, suggesting that RAS blockade may confer chondroprotective and anti-inflammatory benefits via modulation of the NRP-1 axis. Collectively, the findings highlight a potential mechanistic cross-talk between RAS and NRP-1 pathways, offering a promising direction for future studies aimed at developing novel adjunctive strategies for RA management.

Natural polysaccharide-nucleic acid nanocomplex alleviates myocardial infarction by driving chronologically programmed macrophage polarization.

Earthworm protein extract PVESD promotes diabetic wound healing through synergistic regulation of TLR/NF-κB and AMPK pathways.

Diabetic retinopathy is a primary cause of visual impairment in individuals with diabetes and represents a multifaceted process that transcends glucose dysregulation. This review analyzes the interconnected roles of systemic inflammation, lipid metabolism, and the gut-retina axis in retinal vascular and neuronal damage. A systematic search of PubMed and Scopus spanning January 2014 to August 2025, revealed experimental and clinical research associating inflammatory cytokines, lipid dysregulation, and abnormalities in gut microbiota with diabetic retinopathy. Evidence suggests that persistent low-grade inflammation, characterized by elevated levels of interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta, compromises the blood-retinal barrier and accelerates microvascular degeneration. Alterations in lipid pathways, such as reduced docosahexaenoic acid levels, hinder cholesterol efflux and ceramide buildup, exacerbating oxidative stress and neurovascular impairment. Gut microbial dysbiosis diminishes short-chain fatty acid production and fosters endotoxemia, thereby exacerbating retinal inflammation through systemic immune activation. Novel therapeutic strategies that regulate peroxisome proliferator-activated receptor-alpha and restore the microbiota demonstrate synergistic potential to reduce disease progression. The integration of these systems offers a biological foundation for the prevention and therapy of diabetic retinopathy.

Chronic wounds caused by multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) often stall during the healing process due to persistent inflammation and failed tissue repair. This pathological state primarily results from a vicious cycle formed by the interaction of oxidative stress, chronic inflammation, and impaired angiogenesis. To this end, this study employs network pharmacology to reveal that gallic acid (GA, a polyphenol with potent antioxidant and anti-inflammatory activity) promotes skin wound healing by regulating oxidative stress and apoptosis. Subsequently, based on these findings, a dynamic hydrogel dressing with cascade enzyme-like activity was developed. By synergistically modulating the oxidative stress microenvironment, eliminating bacterial infections, promoting angiogenesis, and accelerating the healing of MRSA-infected wounds, it effectively remodels the wound microenvironment. The core of this system is a metal-phenolic network particle (ZCG) self-assembled from Zn2+ (antibacterial), Cu2+ (angiogenic), and GA. These bioactive particles are embedded in a dynamic hydrogel matrix composed of oxidized fucoidan (OFD) and carboxymethyl chitosan (CMCS), which confer self-healing and injectable properties to the dressing. Simultaneously, by synergistically combining metal ions and GA, the hydrogel dressing functions as a "regenerative niche" that effectively eradicates MRSA. It further scavenges excess reactive oxygen species to alleviate inflammation and protect host cells. The system also releases pro-angiogenic copper ions to reconstruct vascular networks, effectively remodeling the wound microenvironment. This promotes collagen deposition and granulation tissue formation, accelerating wound closure. As a universal therapeutic solution for chronic nonhealing wounds, it holds significant clinical translation potential.

Microglia-independent rAAV-induced inflammation causes persistent ocular immune dysregulation rescued by S1P receptor modulation.

Chronic bacterial-infected wounds are difficult to treat due to persistent inflammation, biofilm formation, and antibiotic resistance. Conventional therapeutic approaches, such as systemic or topical antibiotics, are limited by the inability to dynamically monitor drug release at the wound site. To address this issue, we have designed a dual-functional photonic crystal hydrogel (PP/DG@MOF) that not only promotes wound healing by modulating local immune responses and facilitating tissue regeneration but also enables real-time, noninvasive monitoring of drug release and wound healing progress. The PP/DG@MOF hydrogel is embedded with a metal-organic framework possessing both antimicrobial and anti-inflammatory properties (DG@MOF), combined with photonic crystals (PAM-PCH) for visual monitoring of drug release. The DG@MOF hydrogel responds to collagenase activity at the wound site, releasing a mixture composed of ZIF-8 encapsulating the Salvianolic acid B and antimicrobial quaternary ammonium groups, effectively combating bacterial infection at the wound site. As the drug-loaded hydrogel degrades, the embedded photonic crystal layer undergoes tunable structural color changes, providing real-time, noninvasive feedback on drug release and wound healing. This strategy offers a novel approach for the management of chronic infected wounds and holds significant promise for translation into clinical practice as a next-generation wound care material.

Ulcerative colitis (UC) manifests as persistent inflammation and ulceration within the mucosal and submucosal layers of the colon. The present study sought to elucidate the principal targets of Tongbian Baitouweng Decoction (TBD) in UC. A total of 221 TBD-related and 1,270 UC-related genes were retrieved from public databases, with their intersection as candidate targets. Differential expression, machine learning, expression profiling, MR analysis, network construction, molecular docking, enrichment, and immune infiltration analyses were used to refine key targets and explore their functional associations with UC. PPARG, STAT1, and IL1B emerged as the principal targets of TBD against UC. Among UC samples, IL1B and STAT1 were upregulated, whereas PPARG was downregulated. MR analysis revealed significant causal associations: STAT1 (OR = 1.17), IL1B (OR = 0.50), and PPARG (OR = 0.97). A network comprising three targets and 53 corresponding active compounds was established, with molecular docking demonstrating strong binding affinities, particularly with quercetin. Enrichment analysis indicated that the three targets were jointly involved in pathways such as "Toll-like receptor signaling". Immune infiltration analysis revealed that IL1B and STAT1 correlated positively with activated CD4 T cells, macrophages, and natural killer cells, whereas PPARG displayed an inverse pattern. These findings align with existing evidence linking STAT1, PPARG, and IL1B to UC pathogenesis, highlighting TBD's therapeutic potential by targeting key inflammatory and barrier-regulatory pathways; future studies should validate these targets in preclinical models and explore the formula's clinical efficacy in large-scale trials. STAT1, PPARG, and IL1B were TBD's key UC therapeutic targets, with regulatory roles providing a UC research mechanistic framework.

Salpingitis is a leading cause of female infertility and ectopic pregnancy worldwide. Despite advances in reproductive medicine, its early diagnosis and effective prevention of long-term sequelae remain challenging due to its often silent clinical course and complex pathogenesis. This review synthesizes current knowledge on the infectious, immunological, and molecular mechanisms underlying salpingitis, with an emphasis on diagnostic limitations and therapeutic challenges. A comprehensive evaluation of recent literature was conducted focusing on pathogen-induced inflammation, host immune responses, molecular signaling pathways, and emerging diagnostic and therapeutic strategies, including omics-based biomarkers and molecular imaging approaches. Persistent inflammation, cytokine imbalance, and oxidative stress contribute to tubal scarring and ciliary dysfunction, ultimately leading to reproductive failure. While antibiotics are effective in treating acute infection, they do not prevent chronic complications. Advances in molecular diagnostics and non-invasive imaging show promise for early detection, although biomarker validation remains a major limitation. Rising antimicrobial resistance further complicates clinical management. Integrated approaches combining molecular diagnostics, imaging, and targeted therapies are essential to bridge laboratory research and clinical practice. Standardized diagnostic criteria, validated biomarkers, and improved reproductive health equity are critical to reducing the global burden of salpingitis.

Colitis-associated cancer (CAC) arises from persistent intestinal inflammation, immune dysregulation, and microbiota-driven epithelial injury, representing a major link between inflammatory bowel disease and colorectal malignancy. Despite advances in therapy, colon cancer remains one of the leading causes of cancer-related mortality worldwide, underscoring the urgent need for effective preventive and immunomodulatory interventions. Ardisiacrispin B (AB), a bioactive triterpenoid isolated from the Ardisia genus, has been reported to suppress tumor growth by regulating apoptosis and ferroptosis; however, its role in inflammation-driven colorectal tumorigenesis remains unexplored. In this study, we investigated the protective and antitumor effects of AB in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CAC mouse model, with a focus on inflammatory signaling pathways, epithelial remodeling, and gut microbiota modulation. AB administration markedly alleviated disease severity, as evidenced by a significant reduction in disease activity index, including body weight loss, diarrhea, and rectal bleeding. Histopathological evaluation revealed preserved colonic mucosal architecture, diminished inflammatory cell infiltration, and a pronounced reduction in tumor number and size. AB treatment partially modulated the gut microbiota, with a trend toward enrichment of beneficial taxa and a reduction in inflammation-associated bacterial populations. Concurrently, AB robustly downregulated the colonic expression of pro-inflammatory cytokines and chemokines. AB treatment was associated with increased expression of pro-apoptotic markers, indicative of enhanced apoptotic signaling in colonic epithelial cells, as indicated by increased expression of cleaved PARP, cleaved caspase-3, p53, and BAX, while markedly inhibiting cellular proliferation through suppression of Ki-67. Mechanistically, AB was associated with attenuation of key inflammatory and oncogenic signaling pathways, including IL-6/JAK2/STAT3, LPS/TLR4/MyD88/NF-κB, and MAPK cascades. Collectively, Ardisiacrispin B attenuates colitis-associated cancer by rebalancing gut microbiota, suppressing inflammation, and inducing tumor cell apoptosis through inhibition of key oncogenic signaling pathways.

Myelodysplastic syndrome (MDS) corresponds to a heterogeneous group of myeloid neoplasms characterized by ineffective hematopoiesis, persistent cytopenias, and variable risk of progression to acute myeloid leukemia. Evidence accumulated over time indicates that its etiology is multifactorial, involving the interaction between aging of the hematopoietic system, individual susceptibility, and environmental and occupational factors. In this scenario, chronic exposure to environmental chemical agents has emerged as an important risk factor for the development of MDS, especially in agricultural, industrial, and urban contexts. This study aimed to analyze, through a systematic review of the literature, the association between exposure to environmental chemical agents and the risk of MDS, identifying the main agents involved, the most frequent contexts of exposure, and the influence of the type and duration of exposure. The review was conducted according to PRISMA guidelines, with searches in electronic health databases using controlled descriptors and free terms related to MSD, environmental and occupational exposure, and chemical agents. After removing duplicates, studies were selected by screening titles and abstracts, followed by full-text reading, with standardized extraction of methodological and clinical data. The results demonstrated a consistent association between increased risk of MDS and prolonged exposure to pesticides and agrochemicals, herbicides, benzene, organic solvents, industrial and urban pollutants, dioxins, and other substances with genotoxic potential. Agricultural and industrial contexts were most frequently associated with risk, particularly rural and industrial workers and populations residing in environmentally contaminated areas. The duration of exposure proved to be a determining factor, since chronic and cumulative exposures were more strongly associated with the development of the disease than occasional exposures. The literature supports the biological plausibility of these associations, involving mechanisms such as DNA damage, epigenetic changes, oxidative stress, persistent inflammation, and bone marrow microenvironment dysfunction. It is concluded that exposure to environmental and occupational chemical agents is a relevant component in the etiopathogenesis of MDS, reinforcing the need for preventive strategies, occupational health surveillance, and public policies for environmental control, as well as future studies with longitudinal designs and more accurate exposure assessment. Keywords: myelodysplastic syndrome; environmental exposure; occupational exposure; pesticides; benzene; environmental pollution; genotoxic agents; occupational health

ASO Visual Abstract: Persistent Systemic Inflammation Mediates the Impact of Postoperative Complications on Survival after Gastric Cancer Surgery.

ROS-scavenging photothermal hydrogel to remodel the diabetic wound microenvironment and accelerate healing.

Inflammation-responsive DNA hydrogel integrating probiotic outer membrane vesicles for infection monitoring and precision therapy of diabetic wounds.