دامپزشکی
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جستوجوی دقیقدامپزشکی و سلامت واحد
بیماریهای مشترک، سلامت حیوانات و رویکرد سلامت واحد
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بیماریهای مشترک انسان و دام
مقالهها، منابع و پژوهشهای تازه حوزه بیماریهای مشترک انسان و دام
ورود به زیرشاخهسلامت واحد
مقالهها، منابع و پژوهشهای تازه حوزه سلامت واحد
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مقالهها، منابع و پژوهشهای تازه حوزه مدلهای حیوانی
ورود به زیرشاخهبهداشت عمومی دامپزشکی
مقالهها، منابع و پژوهشهای تازه حوزه بهداشت عمومی دامپزشکی
ورود به زیرشاخهتازهترین رکوردها
شواهد دامپزشکی و سلامت واحد
PubMed2028
Closing the Surveillance-to-Stewardship Gap in antimicrobial resistance: a narrative review of global lessons from WHO GLASS, UK ESPAUR, and low- and middle-income countries.
BACKGROUND: Antimicrobial resistance (AMR) surveillance has expanded faster than any other component of the global response, yet resistance continues to rise. In a growing number of settings, the principal constraint is the failure to translate available data into action, a disconnect we describe as the Surveillance-to-Stewardship (S2S) Gap. OBJECTIVES: To define the S2S Gap and its component gaps, examine where it binds across health systems of different maturity, analyse why it persists, and propose an operationalisable, testable framework for closing it. SOURCES: A cross-sectional analysis of WHO GLASS participation across all 55 South Centre member states; the UK ESPAUR programme (2019-2024); published implementation studies from India, Nigeria, and Bangladesh, read alongside three sector-specific systematic syntheses conducted by our group, all now published; and comparative governance analyses and implementation-science frameworks. CONTENT: Adopting the GLASS conception of surveillance (resistance plus antimicrobial use data), the gap recurs but binds at different stages by system maturity: as incomplete surveillance in many low- and middle-income countries (27% (15/55) of the states report both data types), as absent operational stewardship machinery despite near-universal awareness and policy, and as uncertain policy-to-outcome translation in the mature UK system, where a 2% fall in use has not yet been accompanied by falling resistance, for reasons that current data cannot distinguish. Six structural drivers (multi-level governance, diagnostics, workforce, financing, behaviour, and implementation capacity) explain persistence. South Africa illustrates process-level narrowing. The S2S Framework, a five-stage pathway from surveillance to outcomes aligned with CFIR, RE-AIM, and a One Health perspective, enables stage diagnosis and targeted intervention. IMPLICATIONS: Closing the gap requires funding translation as deliberately as data generation, with actions for WHO, governments, health systems, and funders, and an explicit agenda for empirically evaluating the framework itself.
PubMed2027
A Modelling Approach to Resolve Gene Temporal Dynamics in Intestinal Inflammation.
The intestinal epithelium is maintained by stem cells at the crypt base, however, acute or chronic inflammation can severely disrupt stem cell function and tissue homeostasis. To characterize mucosal inflammation and tissue damage, we evaluated time-course gene expression changes using a dextran sulfate sodium (DSS)-induced mouse model of colitis. By applying normalization, Z-score transformation, and spline curve modeling, we trace the temporal expression dynamics of key intestinal genes. This computational approach offer insights into the molecular responses during inflammation and may help identifying new biomarkers for chronic inflammatory diseases.
PubMed2027
A Straightforward and Reliable Mouse Model of Colorectal Cancer by Orthotopic Transplantation.
Colorectal cancer (CRC) is a major malignancy with significant global implications for human health. The development of a reliable and pathologically relevant orthotopic CRC model is essential for advancing our understanding of its molecular mechanisms and for developing more effective therapeutic interventions. However, the construction of such models is fraught with challenges primarily because of the technical complexities involved in the transplantation of CRC cells into the intestinal epithelium. In this chapter, we describe a recently developed method for generating an orthotopic CRC model within the mouse cecal epithelium. This model enables tumor development and progression within a natural tissue microenvironment and facilitates complex interactions between tumor cells and surrounding normal cells, thereby replicating the intratumor heterogeneity of CRC. All procedures in this method are visualized under stereomicroscopic observation, leading to the efficient engraftment of CRC cells and subsequent tumor development. The establishment of this reliable orthotopic CRC model, which mimics tumor development in a more natural microenvironment, offers new opportunities to explore the molecular mechanisms underlying CRC and to assess novel anticancer therapies in pathologically relevant contexts.
PubMed2027
Global Genomic Surveillance.
Global genomic surveillance has emerged as a foundational pillar of public health in the twenty-first century, enabling real-time tracking of pathogen evolution and informing outbreak response. This chapter examines the strategic architecture of global genomic surveillance, focusing on its application to arboviruses such as chikungunya virus (CHIKV). It explores the integration of genomic data with epidemiological, clinical, and environmental information within a One Health framework, while addressing critical challenges in governance, equity, and interoperability. The discussion covers the entire genomic surveillance workflow, from sample collection and sequencing to bioinformatic analysis and phylogenetic inference, and highlights the transformative role of artificial intelligence (AI) in predictive surveillance. By analyzing global initiatives, operational barriers, and emerging technologies, this chapter underscores the necessity of sustainable, equitable, and interoperable genomic systems to proactively address current and future infectious disease threats.
PubMed2027
Immunophenotyping Studies in Nonhuman Primate Models.
Nonhuman primate (NHP) models are important in biomedical research due to their close evolutionary relationship with humans, which provides a high degree of anatomical, genetic, and physiological similarity. This close resemblance is particularly valuable for studying complex biological processes and diseases that are difficult to model in other animals. NHPs have hematopoietic and immune systems that closely mirror those of humans, making them crucial for researching hematopoietic stem cell biology, immunology, infectious diseases, and vaccine development, offering insights that are more likely to translate to human health. With the rapid development of immunotherapy, the NHP model serves as an invaluable tool for preclinical studies of immunotherapy. Immunophenotyping, the process of characterizing and quantifying hematopoietic cell populations and their functional states, is critical in studies related to the hematopoietic and immune system. While the NHP model is the most relevant animal model for human biology, the immunophenotyping methods used may not always align with those employed for human samples. This chapter provides a comprehensive overview of key considerations for conducting immunophenotyping studies using NHP models, particularly in the rhesus macaque model. It covers methodological aspects, including sample preparation, the selection and validation of appropriate antibody clones, the application of flow cytometry techniques, and the data analysis to ensure high-quality and reproducible results. By providing a comprehensive overview of these considerations, this chapter aims to equip researchers with the knowledge needed to effectively utilize rhesus macaque NHP models in immunophenotyping studies, ultimately enhancing the translational impact of their findings on human health.
PubMed2027
Quantifying Chlamydia in the Mouse Gastrointestinal Tract.
Chlamydia trachomatis (CT) causes genital tract infection in humans, but the clinical significance of C. trachomatis detection in the gastrointestinal (GI) tract is an area of active research. Chlamydia muridarum (CM) is a mouse-adapted species used to investigate chlamydial biology and pathogenicity in both the genital and gastrointestinal tracts. Since chlamydial colonization of different segments of the GI tract may lead to distinct consequences, quantifying chlamydial yields across these regions will facilitate understanding of chlamydial biology and pathogenicity. This chapter describes a step-by-step protocol to isolate and process GI tract tissue in a CM mouse model of infection and quantify the infectious yields of chlamydia.
PubMed2026
A Notch signaling antagonist (DAPT) ameliorates autoimmune arthritis in mice by suppressing Th1 and Th17 immune responses.
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease for which targeted therapies remain limited. The Notch signaling pathway has been implicated in T cell differentiation and autoimmune inflammation. OBJECTIVES: This study aimed to investigate the therapeutic effects of the Notch signaling antagonist DAPT on autoimmune arthritis in mice and to explore its underlying immunological mechanisms. METHODS: A collagen-induced arthritis (CIA) mouse model was established. DAPT (100 ng/kg) or PBS was administered intraperitoneally every other day from day 0 to day 36. Notch pathway activation in CD4+ T cells and synovial tissues was assessed by Western blot and immunohistochemistry. Arthritis severity was evaluated by clinical scoring, radiological examination and histopathology. Th1, Th17 and Treg cell frequencies and absolute numbers in spleen and lymph nodes (LNs) were analyzed by flow cytometry. Plasma cytokine levels were measured by multiplex assay. In-vitro Th17 differentiation assays were performed with DAPT or a Notch agonist. RESULTS: Compared with normal mice, CIA mice showed significant upregulation of NICD expression in CD4+ T cells and synovial tissues. DAPT treatment significantly reduced clinical arthritis scores, joint erosion and cartilage destruction. DAPT also decreased the frequencies and absolute numbers of Th1 and Th17 cells in the spleen and LNs, alongwith reduced plasma levels of IFN-γ and IL-17. In-vitro, DAPT suppressed Th17 differentiation, while Notch agonist enhanced it. Treg cells were not significantly altered by DAPT. CONCLUSION: The Notch signaling antagonist DAPT ameliorates autoimmune arthritis in mice by suppressing Th1 and Th17 immune responses, highlighting Notch signaling as a potential therapeutic target for RA.
PubMed2026
Artemisinin alleviates hippocampal neuronal apoptosis and cognitive impairment in rats after cardiac arrest resuscitation: Association with the PI3K/Akt pathway.
BACKGROUND: Cardiac arrest (CA) is associated with high mortality and severe neurological sequelae. Artemisinin (ARS), a natural product from Artemisia annua, has potential neuroprotective effects, but its role in brain injury after CA resuscitation remains unclear. OBJECTIVES: This study investigated the effects of ARS on hippocampal neuronal apoptosis and cognitive dysfunction in rats after CA resuscitation and explored whether these effects are associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: Sixty male rats were randomly assigned to six groups: sham, model, artemisinin (40 mg/kg), dimethyl sulfoxide ((DMSO, 100 mg/kg), LY294002 (a phosphatidylinositol 3-kinase inhibitor, 25 mg/kg) and artemisinin plus LY294002. Cardiac arrest was induced by transcutaneous electrical stimulation. Outcome assessors were blinded. Neurological function was evaluated using the Neurological Deficit Scale. Hippocampal damage and apoptosis were assessed by hematoxylin and eosin staining and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Learning and memory were tested using novel object recognition and the Morris water maze. Protein expression was measured by Western blot. RESULTS: Artemisinin significantly improved Neurological Deficit Scale scores, reduced terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and alleviated hippocampal damage. Artemisinin also prolonged novel object exploration time, shortened escape latency, increased target quadrant time and upregulated phosphatidylinositol 3-kinase expression and the ratio of phosphorylated protein kinase B to protein kinase B. Co-administration of LY294002 partially reversed these effects. CONCLUSION: Artemisinin alleviates hippocampal neuronal apoptosis and improves neurological deficits and cognitive dysfunction in rats after cardiac arrest resuscitation, suggesting a possible association with activation of the phosphatidylinositol 3-kinase/protein kinase B pathway. Limitations include use of a single pharmacological inhibitor and lack of genetic validation.
PubMed2026
ATI-2341 TFA promotes acquisition of epithelial-like immunophenotype in bone marrow mesenchymal stem cells and alleviates intrauterine adhesion in a rat model.
BACKGROUND: Intrauterine adhesion (IUA) is a common complication of endometrial injury. Bone marrow mesenchymal stem cells (BMSCs) have been implicated in endometrial repair, but strategies to enhance their therapeutic efficacy remain to be optimized. The C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12) axis plays a pivotal role in BMSC homing. OBJECTIVE: This study aimed to test the hypothesis that ATI-2341, a functionally selective allosteric regulator of CXCR4, enhances the therapeutic efficacy of BMSCs in a rat IUA model. METHODS: After establishing the endometrial injury model, rat BMSCs were extracted and treated with ATI-2341 TFA (100 ng/mL). IUA model rats were randomly divided into model control group, BMSCs group, BMSCs+ATI-2341 TFA group, BMSCs+PBS group and Positive control group (n=10 each). Endometrial thickness was assessed by hematoxylin and eosin (HE) staining; cell proliferation by the methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) protein expression by Western blot; and cytokeratin and vimentin expression by immunohistochemistry. RESULTS: ATI-2341 TFA-pre-treated BMSCs significantly increased endometrial thickness compared to untreated BMSCs (P < 0.05) or estrogen (P < 0.05). ATI-2341 TFA enhanced BMSC proliferation at 48 h (P < 0.05) and 72 h (P < 0.05). BMSCs exposed to ATI-2341 TFA or estrogen exhibited strong cytokeratin positivity and vimentin negativity. MMP-9 was downregulated (P < 0.05) and TIMP-1 upregulated (P < 0.05) in the ATI-2341 TFA group relative to controls. CONCLUSION: ATI-2341 TFA promotes acquisition of epithelial-like immunophenotype in BMSCs within the injured endometrial microenvironment and is associated with improved endometrial morphology in IUA rats. These findings provide preliminary evidence for the functional modulation of BMSCs by CXCR4-targeted therapy in endometrial repair.
PubMed2026
Compound Miao medicine Jiuxian Luohan bone-setting decoction improves rat femoral fracture healing: Associations with osteogenic and apoptosis-related markers.
BACKGROUND: Fracture healing is a dynamic biological process involving inflammation, callus formation, mineralization and remodeling. Osteogenic and apoptosis-related markers may reflect changes during repair, but tissue-level marker expression alone does not establish a causal apoptotic mechanism. OBJECTIVES: To evaluate whether Compound Miao medicine Jiuxian Luohan bone-setting decoction is associated with improved femoral fracture healing in rats and with altered expression of runt-related transcription factor 2 (Runx2), Osterix, procollagen type I N-terminal propeptide (PINP), Bcl-2-associated X protein (Bax) and Caspase-3 at the fracture site. METHODS: Twenty-five male specific-pathogen-free (SPF) Sprague-Dawley rats were used to establish a right femoral fracture model and were randomized into five groups (n=5/group): model, low-, medium- and high-dose decoction and orthopedic bone-setting tablet groups. Treatments were initiated 24 h after modeling and administered by gavage twice daily for 30 days. Anteroposterior and lateral radiographs were obtained on day 15 and scored using the Lane-Sandhu system. Fracture-site tissues were collected on day 30 for reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blotting, immunohistochemistry and Alizarin Red staining. RESULTS: Compared with the model group, the high-dose decoction group showed a higher Lane-Sandhu score at week 2 and greater callus formation. Runx2, Osterix and PINP mRNA/protein levels increased, whereas Bax and Caspase-3 mRNA/protein levels decreased in treated groups, particularly in the high-dose group. Alizarin Red staining indicated greater deposition of mineralized matrix in treated tissues. CONCLUSION: Compound Miao medicine Jiuxian Luohan bone-setting decoction was associated with improved radiographic healing and favorable changes in osteogenic and apoptosis-related markers in this rat femoral fracture model.
PubMed2026
Madecassic acid attenuates sepsis-associated acute lung injury by regulating the PI3K/AKT/mTOR pathway to mediate anti-inflammatory, antioxidant and anti-apoptotic effects.
BACKGROUND: Sepsis-induced acute lung injury (ALI) is a critical illness with a high mortality rate. Madecassic acid (MA), a pentacyclic triterpenoid extracted from Centella asiatica, exhibits multiple biological activities, but its role in sepsis-associated ALI remains poorly elucidated. OBJECTIVES: The aim of this study was to investigate the protective effect of MA on lipopolysaccharide (LPS)-induced ALI in mice and to elucidate its potential mechanisms in regulating inflammation, oxidative stress, apoptosis and the PI3K/AKT/mTOR signaling pathway. METHODS: An ALI mouse model was established by intraperitoneal LPS injection. The mice were randomly divided into a sham operation group, an MA alone group, an LPS model group and an LPS combined with MA treatment group. The degree of lung injury was assessed via histopathological examination of the lungs and the lung wet/dry weight ratio; the levels of inflammatory factors (TNF-α and IL-6) and oxidative stress markers (MPO, MDA, SOD and GSH-Px) in the bronchoalveolar lavage fluid (BALF) were measured; and the expression of apoptosis-related proteins and PI3K/AKT/mTOR pathway activation in the lung tissues were detected via Western blotting. RESULTS: MA treatment significantly reduced LPS-induced lung tissue injury, edema and inflammatory cell infiltration; decreased the levels of proinflammatory factors (TNF-α and IL-6); improved oxidative stress parameters (decreased MPO and MDA levels and increased SOD and GSH-Px levels); inhibited apoptosis (downregulated Bax and cleaved caspase-3 expression and upregulated Bcl-2 expression); and inhibited the phosphorylation of PI3K, AKT and mTOR. CONCLUSION: MA attenuates sepsis-associated ALI through anti-inflammatory, antioxidant and anti-apoptotic effects and this mechanism is related to inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. MA has the potential to be a therapeutic agent for sepsis-associated ALI.
PubMed2026
Site-specific transdermal delivery of Qingteng Waifu San in a rheumatoid arthritis rabbit model.
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint swelling, pain, cartilage destruction and bone erosion. Qingteng Waifu San is an external sinomenine-containing preparation, but its site-specific transdermal response requires disease-relevant evaluation. OBJECTIVES: To compare Zusanli (ST36)-site and adjacent non-acupoint transdermal application of Qingteng Waifu San in an ovalbumin/complete Freund's adjuvant-induced RA rabbit model and to evaluate formulation, neuropeptide, inflammatory, behavioural and histopathological outcomes. METHODS: Forty-eight New Zealand white rabbits were allocated into six groups (n=8 each): normal control, vehicle-only transdermal control, acupuncture, acupoint injection, ST36-site transdermal Qingteng Waifu San and adjacent non-acupoint transdermal Qingteng Waifu San. Gel appearance, pH, viscosity, spreadability, sinomenine content and high-performance liquid chromatography (HPLC) fingerprint similarity were assessed. Substance P (SP), calcitonin gene-related peptide (CGRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA). SP and CGRP messenger RNA (mRNA) were analysed by real-time polymerase chain reaction (PCR). Arthritis score, paw volume, mechanical withdrawal threshold and histopathological scores were assessed. RESULTS: The vehicle-only group showed RA-related changes compared with normal controls. ST36-site Qingteng Waifu San reduced arthritis score, paw volume, serum cytokines and histopathological injury scores and improved mechanical withdrawal threshold compared with vehicle-only control. SP and CGRP levels were higher after ST36 application than after adjacent non-acupoint application, indicating site-dependent neurocutaneous modulation. CONCLUSION: ST36-site transdermal Qingteng Waifu San produced stronger neuropeptide modulation and more favourable RA-related outcome profiles than adjacent non-acupoint application.
PubMed2026
A One Health Molecular Investigation and Exploratory Epidemiological Analysis of Cryptosporidium spp. in A Shared Human-Animal Ecosystem.
INTRODUCTION: Cryptosporidium spp. are enteric protozoan parasites of public health importance, particularly in low-resource settings where humans, animals and environmental water sources frequently interact. This study investigated the prevalence, molecular diversity and environmental exposure-related variables in relation to Cryptosporidium infection in a rural community. METHODS: A cross-sectional study was conducted using 180 faecal samples collected from humans, cattle, chickens, fish, cats, dogs, and ducks. Speciation and subtyping were determined through PCR amplification and sequencing of the 18S rRNA and gp60 genes. Epidemiological and environmental data were collected, and univariable analyses were conducted. An exploratory multivariable logistic regression model was subsequently performed for the human subset. RESULTS: The overall prevalence of Cryptosporidium infection was 9.40%, with the highest rates observed in humans (14.8%) and cattle (13.5%). Molecular characterisation identified C. hominis, C. parvum, C. bovis and C. felis. Among humans, C. hominis was the predominant, whereas C. parvum was also detected, including mixed infections. gp60 analysis identified multiple subtype families, including Ia, Ib, IIa, IIc and IId. Phylogenetic analysis demonstrated close genetic relationships between Bangladeshi isolates and previously reported reference strains from South Asia and the Middle East. Higher odds of Cryptosporidium infection were observed among individuals reporting river bathing and consumption of untreated water, whereas lower odds were observed among those reporting regular handwashing. No statistically significant associations were identified between evaluated environmental variables and infection among non-human hosts. CONCLUSION: The study demonstrated the circulation of multiple Cryptosporidium species and subtype families within a shared human-animal ecosystem. The contaminated surface water and inadequate hygiene practices may represent important environmental exposure interfaces for Cryptosporidium infection in the study area. However, given the cross-sectional design and limited number of positive cases, the epidemiological findings should be interpreted as exploratory associations rather than definitive transmission pathways. Further longitudinal One Health investigations are needed.
PubMed2026
AKAP12 Regulates Perivascular OPC Accumulation in the Corpus Callosum During Cerebral Hypoperfusion.
Oligodendrocyte precursor cells (OPCs) have been reported to interact with cerebral microvessels, but the extent and spatiotemporal regulation of this relationship across maturation and hypoperfusion-induced stress remain incompletely defined. Here, we quantified OPC-vessel relationships in the mouse corpus callosum using PDGFR-α/OLIG2/CD31 immunohistochemistry and distance-based spatial analysis, classifying OPCs within 10 μm of CD31+ vessels as perivascular OPCs. We show that while total OPC density decreases from development to adulthood, the proportion of perivascular OPCs increases in the mature brain. Under cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS), OPC density and the enrichment of perivascular OPCs were increased by Day 7 and remained elevated through Days 14-28. Proliferative OPCs (Ki67-positive OPCs) were preferentially observed within the vessel-proximal domain, indicating that the perivascular compartment functions as a stress-responsive proliferative niche. To identify regulators of this response, we focused on A-kinase anchoring protein 12 (AKAP12), a scaffolding protein expressed in vascular cells. In middle-aged Akap12 global knockout mice subjected to BCAS, hypoperfusion-induced OPC increase was preserved, but perivascular accumulation was reduced. This defect was accompanied by increased IgG leakage without a corresponding reduction in vascular area density, suggesting that AKAP12 supports the integrity of the perivascular microenvironment required for OPC niche remodeling. Together, these findings reveal the perivascular niche as a hypoperfusion-responsive compartment for OPC activation and suggest that AKAP12-dependent vascular barrier integrity contributes to the maintenance of this oligovascular niche.
PubMed2026
Astrocytic PDE7B Drives Blood-Brain Barrier Breakdown via Extracellular Vesicles in Demyelinating Disease.
Blood-brain barrier (BBB) dysfunction is a critical driver of neuroinflammation and demyelination, yet its cellular and molecular underpinnings remain poorly defined. Here, we identify a pathogenic subpopulation of astrocytes expressing phosphodiesterase 7B (PDE7B) that contributes to BBB disruption. Using a colitis-induced BBB opening model and single-cell RNA sequencing, we found PDE7Bhigh astrocytes enriched at sites of BBB breakdown. In both human demyelinated lesions and the experimental autoimmune encephalomyelitis mouse model, elevated astrocytic PDE7B expression correlated with vascular leakage. In vivo and in vitro experiments confirmed that astrocytic PDE7B impairs BBB integrity, in part via effects on endothelial cells. Mechanistically, elevated PDE7B promotes BBB disruption through astrocyte-derived extracellular vesicles enriched in miR-155-5p, which disrupts endothelial tight junction integrity and focal adhesion-associated signaling. These findings identify astrocytic PDE7B as a regulatory and therapeutic target of neurovascular integrity and provide new insight into how glial signaling contributes to BBB dysfunction in demyelinating diseases.
PubMed2026
Bone marrow mesenchymal stem cells relieve rheumatoid arthritis by blocking JAK/STAT and TLR-4/NF-κB pathways.
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and joint destruction. Bone marrow mesenchymal stem cells (BMSCs) have shown therapeutic potential in RA, but the underlying mechanisms remain poorly understood. OBJECTIVES: To investigate the effects of BMSCs on human RA fibroblast-like synovial MH7A cells and complete Freund's adjuvant (CFA)-induced arthritis in rats and to explore the involvement of the JAK/STAT and TLR-4/NF-κB signaling pathways. METHODS: BMSCs were isolated and co-cultured with MH7A cells. CFA-induced arthritis rat models were established. MH7A cell viability, inflammatory cytokine levels, paw withdrawal thermal latency (PWTL), gait parameters and the expression of JAK/STAT and TLR-4/NF-κB pathway-related genes and proteins were assessed. RESULTS: In-vitro, BMSC co-culture significantly inhibited MH7A cell viability and reduced TNF-α, IL-6 and IL-8 levels. BMSC treatment also downregulated the expression of JAK2, p-JAK2, STAT3, p-STAT3, TLR4, P65 and p-P65 in MH7A cells. In-vivo, BMSC administration improved PWTL and gait parameters, reduced serum inflammatory cytokine levels and suppressed the expression of JAK/STAT and TLR-4/NF-κB pathway components in synovial tissues of CFA-induced arthritic rats. CONCLUSION: BMSCs alleviate RA by inhibiting inflammatory responses in vitro and in vivo and the underlying mechanism may involve blockade of the JAK/STAT and TLR-4/NF-κB signaling pathways.
PubMed2026
Comparative Evaluation of Plumbagin and Sorafenib in NDEA-TAA-Induced Hepatocellular Carcinoma: Effects on Hepatic Function, Redox Homeostasis and Histopathology.
Hepatocellular carcinoma (HCC) is a major contributor to cancer-related mortality worldwide and is closely linked to oxidative stress and progressive hepatic dysfunction. This study investigated the effects of plumbagin on antioxidant defense systems and hepatic function markers in an N-nitrosodiethylamine-thioacetamide (NDEA-TAA)-induced experimental model of HCC and compared its efficacy with that of sorafenib. Male Wistar rats were assigned to five groups: normal control, plumbagin-only, HCC control, HCC treated with plumbagin, and HCC treated with sorafenib. Hepatocarcinogenesis was induced using NDEA-TAA, after which antioxidant parameters including reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) were evaluated alongside hepatic function markers alanine aminotransferase (ALT) and albumin (ALB). The HCC control group exhibited significant reductions in GSH, GST, GPx, CAT, and SOD activities, accompanied by elevated MDA and ALT levels and decreased ALB concentrations (p ≤ 0.05), indicating severe oxidative stress and hepatic injury. Treatment with plumbagin significantly restored antioxidant enzyme activities, reduced lipid peroxidation, and improved hepatic function relative to the untreated HCC group. These effects were comparable to, and in certain parameters exceeded, those observed following sorafenib administration. The findings demonstrate that plumbagin possesses substantial antioxidative and hepatoprotective properties capable of mitigating oxidative damage and improving liver function in experimental HCC. These findings support further investigation of plumbagin as a redox-modulating candidate in HCC and a basis for future studies incorporating combination treatment, molecular validation and translational models.
PubMed2026
Dichloroacetate Improves Animal Survival, Growth, Neuromuscular Activity, Mitochondrial Stress and Physiology, and Elevated Lactate in C. elegans pdha-1 and dld-1 RNAi Models of Pyruvate Dehydrogenase Complex Deficiency (PDCD).
Pyruvate dehydrogenase complex (PDHc) deficiency (PDCD) is a primary mitochondrial disorder characterized by neurodevelopmental disability, altered intermediary metabolism, and early mortality. Dichloroacetate (DCA), a pyruvate analog, activates PDHc and remains under clinical investigation for treatment of PDCD. Here, we studied the in vivo efficacy of a five-point log concentration range of DCA on animal health and metabolism in C. elegans with feeding RNA interference (RNAi) expression knockdown of either PDHA-1 or DLD-1 homologs at graded degrees to model variable disease severity. These worm models recapitulate phenotypic features of PDCD observed in human patients, including reduced survival, delayed growth, locomotor impairment, and elevated lactate and/or pyruvate tissue levels. DCA treatment appeared well-tolerated, with no gross morphologic toxicity seen at doses up to 25 mM. Significantly improved health, survival, tissue lactate levels, and mitochondrial physiology were observed at 25 mM in pdha-1(RNAi) knockdown animals. DCA treatment in dld-1(RNAi) C. elegans models (undiluted, 1:20 dilution, and 1:100 dilution) significantly improved survival, neuromuscular function, and metabolic phenotypes primarily in the moderate (1:20) and/or mild (1:100) dld-1(RNAi) deficiency strains, but not in full-dose dld-1(RNAi). Importantly, linear growth, neuromuscular activity, and mitochondrial physiology were significantly improved with DCA treatment even in the most severe dld-1(RNAi) undiluted model. Overall, preclinical modeling provides objective evidence of DCA therapeutic efficacy in C. elegans knockdown strains for two well-conserved homologs of PDHA1 and DLD representing distinct genetic etiologies of PDCD, with demonstrated beneficial effects on survival, healthspan, tissue lactate, and mitochondrial physiology. These data further confirm that DCA's therapeutic effect correlates with PDHc disease phenotype severity in dld-1(RNAi) animals.
PubMed2026
Duo Nang Decoction enhances endometrial receptivity in PCOS rats by upregulating caveolin-1 expression.
BACKGROUND: Duo Nang Decoction (DND) is widely used for treating polycystic ovary syndrome (PCOS)-related infertility. However, the molecular mechanisms underlying its action remain unclear. In a previous study, downregulation of caveolin-1 (Cav-1) was shown to impair endometrial angiogenesis, a key determinant of endometrial receptivity. OBJECTIVES: This research study aimed to elucidate the influence and potential molecular mechanisms of DND on endometrial receptivity, specifically focusing on Cav-1 in PCOS rats. METHODS: Sprague Dawley (SD) rats (females, 3-week-old) were randomly categorized into the DND and aspirin cohorts. After successful PCOS modeling, the rats were orally administered DND or aspirin, respectively. Then, ovulation was induced and mating was performed. The rats were euthanized on the 2nd and 5th day of conception and the endometrium was extracted for histological evaluation via hematoxylin and eosin (HE) staining. Furthermore, immunohistochemistry (IHC) staining was carried out to assess Cav-1, vascular endothelial growth factor (VEGF) and β-catenin levels, as well as endometrial microvascular density (MVD). Moreover, reverse transcription polymerase chain reaction (RT-PCR) was used to measure the mRNA levels of VEGF and Cav-1 in the endometrium of both groups. RESULTS: The HE and IHC staining, as well as RT-PCR analysis of endometrial tissue slices, revealed that on the 2nd and 5th day of conception, both groups indicated significantly increased endometrial thickness, MVD and elevated levels of VEGF, Cav-1 and β-Catenin. However, the MVD in the DND group was substantially higher relative to the aspirin group. CONCLUSION: This study revealed that DND significantly enhanced endometrial angiogenesis and improved endometrial receptivity in PCOS rats. Mechanistically, the effects of DND on endometrial receptivity may be associated with the upregulation of Cav-1 and β-catenin. However, the specific mechanism of action warrants further research.
PubMed2026
Glial Dysfunction and Memory Impairments in a Model of Pediatric Obstructive Sleep Apnea.
Pediatric obstructive sleep apnea (POSA) is a common childhood disease that often causes aberrant brain development and cognitive deficits. The pathophysiological underpinnings of cognitive impairments in POSA remain unclear. Here, we examined cellular and molecular aspects of pathology in a mouse model of POSA that features learning and memory deficits. We performed single-nucleus RNA-sequencing (snRNA-seq) of the hippocampus to examine gene expression changes in an unbiased and cell type-specific manner. This dataset revealed a striking perturbation of transcriptomes across all brain cell types, particularly within glia and neural stem cells. We validated reduced expression of several differentially expressed genes at protein level: QDPR and SOX8 in oligodendrocytes, LRRK2 and NDUFS4 in neural stem cells, TFE3 in microglia, and GLUT1 in astrocytes. Comparison of oligodendrocyte gene expression changes with proteomic datasets suggested impairments in myelination, which we confirmed in vivo. Furthermore, cellular level analyses demonstrated aberrant morphology of oligodendrocytes, astrocytes, and microglia in the hippocampus, and diminished numbers of neural stem cells in the subgranular zone. Our study identifies cellular and molecular glial cell dysfunction in POSA, validates gene targets for further study, and provides an snRNA-seq dataset to facilitate further data-driven hypothesis generation.
PubMed2026
Hematopoietic protective effects of Guiqi crucian carp decoction on chemotherapy-induced leukopenia in rats.
BACKGROUND: Chemotherapy-induced leukopenia is a common dose-limiting toxicity that compromises treatment continuity and increases the risk of infection. Current pharmacological interventions are often associated with adverse effects, highlighting the need for safe and effective supportive strategies. Guiqi crucian carp decoction (GQCCD), a traditional dietary therapy derived from the concept of medicine-food homology, has been used to replenish qi and nourish blood; however, its hematopoietic protective effects have not been systematically evaluated. OBJECTIVES: This study aimed to investigate the hematopoietic and immunoprotective effects of GQCCD in a rat model of chemotherapy-induced leukopenia. METHODS: A leukopenia model was established in rats using 5-fluorouracil (5-FU). Rats were divided into a blank control group, model group, positive control group (batyl alcohol) and GQCCD-treated group. Peripheral blood parameters, including white blood cell (WBC), neutrophil (NE UT), lymphocyte (LYMPH) and monocyte (MONO) counts, were measured at different time points. Thymus and spleen indices were calculated and histopathological examinations of bone marrow, spleen and thymus were performed. RESULTS: 5-FU administration induced significant leukopenia, accompanied by reduced thymus and spleen indices and marked histopathological damage in immune organs and bone marrow. Compared with the model group, GQCCD treatment significantly increased WBC and NEUT counts and MONO percentage (P < 0.01), along with significant improvements in thymus and spleen indices (P < 0.01). Histopathological analysis revealed substantial restoration of bone marrow and immune organ structures. No statistically significant improvement in LYMPH counts was observed. CONCLUSION: GQCCD effectively alleviated chemotherapy-induced leukopenia in rats by restoring peripheral blood parameters, improving immune organ indices and ameliorating bone marrow and immune organ damage. These findings support the potential of GQCCD as a complementary dietary therapy for managing chemotherapy-related myelosuppression.
PubMed2026
Maresin 2 Attenuates Hypertensive Vascular Remodeling via Inhibiting Macrophage Infiltration and Pro-fibrotic Polarization.
Immune-inflammatory responses are pivotal regulators of hypertensive vascular remodeling. Specialized pro-resolving mediators (SPMs), including Maresin 2 (MaR2), are endogenous anti-inflammatory molecules. However, the specific role of MaR2 in regulating hypertension and vascular remodeling, as well as its underlying mechanisms, remains unclear. In this study, a murine model of hypertension was induced by continuous infusion of Angiotensin II (AngII) at 1 μg/kg/min. MaR2 intervention (2 μg/kg/day) was administered either prophylactically (before model induction) or therapeutically (after model induction). Prophylactic MaR2 effectively prevented AngII-induced blood pressure elevation and vascular remodeling. Similarly, therapeutic administration after the establishment of hypertension with MaR2 significantly lowered blood pressure and attenuated medial thickening and fibrosis in the aorta and mesenteric arteries. Mechanistic studies revealed that MaR2 significantly inhibited macrophage infiltration and inflammatory responses within vascular tissues. Further in vitro and in vivo experiments confirmed that MaR2 effectively suppressed AngII-induced macrophage polarization toward a pro-fibrotic phenotype and reduced the acquisition of a myofibroblast-like phenotype (i.e., α-SMA expression) by macrophages by blocking the TGF-β/Smad3 signaling pathway. Notably, pharmacological activation of TGF-β/Smad signaling using SRI011381 partially counteracted the protective effects of MaR2 on vascular remodeling. MaR2 attenuates AngII-induced hypertension and vascular remodeling in association with reduced vascular macrophage accumulation and suppression of macrophage pro-fibrotic polarization, at least partly through regulation of TGF-β/Smad3 signaling. These findings identify MaR2 as a candidate pro-resolving intervention in an AngII-induced murine model of hypertension and support further mechanistic and translational evaluation in hypertension-associated vascular remodeling.
PubMed2026
Molecular mechanism of ephedrine-regulated ferroptosis in asthma via PKM2-ACSL4 lactylation.
BACKGROUND: Asthma is a chronic airway inflammatory disease with limited curative options. Ephedrine (EP), a natural alkaloid, has shown anti‑asthmatic effects, but its molecular mechanism remains incompletely understood. Ferroptosis, an iron‑dependent lipid peroxidation cell death pathway, aggravates airway epithelial injury in asthma. Pyruvate kinase M2 (PKM2) generates lactate, which can drive protein lactylation; however, whether EP acts by modulating PKM2-dependent lactylation of acyl-CoA synthetase long-chain family member 4 (ACSL4) to inhibit ferroptosis is unknown. OBJECTIVES: To investigated whether EP attenuates ferroptosis-driven asthmatic progression by suppressing PKM2-dependent lactylation of ACSL4. METHODS: LPS-stimulated BEAS-2B cells and ovalbumin (OVA)-sensitized rats were used as in-vitro and in-vivo asthma models, respectively. Cell proliferation (CCK-8), apoptosis (TUNEL), inflammatory cytokines (ELISA) and oxidative/lipid peroxidation markers (ROS, Fe²⁺, MDA, LPO, SOD) were measured. PKM2 and ACSL4 expression were determined by qPCR and Western blot; ACSL4 lactylation was assessed by co-immunoprecipitation. In-vivo, asthma behavioral scores, airway resistance (RL), dynamic compliance (Cdyn), lung histology (HE) and bronchoalveolar lavage fluid cytokines were evaluated. RESULTS: In-vitro, EP restored cell viability, reduced apoptosis and cytokine release and inhibited ferroptosis (P < 0.05). LPS upregulated PKM2; EP reversed this, whereas PKM2 overexpression abolished EP's protection (P < 0.05). PKM2 overexpression increased ACSL4 transcription and lactylation, effects attenuated by EP. Silencing ACSL4 reversed PKM2 overexpression‑induced injury and ferroptosis (P < 0.05). In-vivo, EP alleviated OVA‑induced asthmatic symptoms and pulmonary pathological changes. CONCLUSION: EP mitigates asthma by down-regulating PKM2, thereby blocking ACSL4 lactylation and ferroptosis-mediated airway epithelial injury. The PKM2‑ACSL4 lactylation axis represents a novel therapeutic target.
PubMed2026
MRI Visualization of Melatonin-Promoted Oligodendrogenesis and Its Neuroprotective Effects in Preterm White Matter Injury Rat Model.
Preterm white matter injury (PWMI) is a serious neurologic condition that threatens neonatal survival and severely impairs the cognitive and motor development of affected children. Melatonin (Mel), a neuroendocrine hormone with anti-inflammatory and antioxidant properties, has shown neuroprotective potential in neonatal brain injury, although the mechanisms underlying its effects in PWMI remain incompletely understood. In this study, we established a neonatal rat model of PWMI and combined multimodal magnetic resonance imaging (MRI) with histological analyses to investigate the effects of Mel on oligodendrocyte precursor cells (OPCs) proliferation, differentiation, and subsequent white matter development. We discovered that Mel administration increased cerebral oxygenation and blood flow, thereby altering the cerebral metabolic microenvironment and mitigating white matter damage caused by hypoxic-ischemic injury. Moreover, Mel promoted the proliferation of OPCs and exerted neuroprotective effects by activating the protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK-3β)/β-catenin signaling pathway. In addition, Mel treatment facilitated neural fiber formation in distant white matter regions of PWMI models, ultimately alleviating cognitive and motor impairments in affected rats. Collectively, these findings suggest that Mel facilitates oligodendrogenesis and white matter repair after PWMI, at least in part through modulation of the AKT/GSK-3β/β-catenin pathway. Multimodal MRI can provide a useful noninvasive approach for monitoring treatment-related changes in white matter injury and development, supporting further investigation of Mel as a potential therapeutic strategy for PWMI.
PubMed2026
Nerandomilast is Associated With Altered Alveolar Epithelial Cell State Dynamics While Attenuating Fibrotic Remodeling in Pulmonary Fibrosis.
Pulmonary fibrosis is a progressive and life-threatening lung disorder characterized by excessive fibrogenesis and impaired respiratory function. Nerandomilast, a preferential phosphodiesterase 4B inhibitor, is currently approved for the treatment of idiopathic pulmonary fibrosis and progressive pulmonary fibrosis in several countries following its demonstrated clinical efficacy in Phase III trials. However, its cellular mechanisms of action remain incompletely understood. In this study, we investigated the effects of nerandomilast on a bleomycin-induced mouse model of lung fibrosis. Nerandomilast treatment attenuates fibrotic remodeling and preserves alveolar epithelial architecture. Single-cell transcriptomic analyses revealed altered alveolar epithelial cell state dynamics accompanied by increased cell cycle-associated pathways in alveolar type 2 cells and an increased relative abundance of alveolar type 2 cells. Consistent with the single-cell findings, nerandomilast was associated with an increased SFTPC-positive area and the preservation of alveolar epithelial architecture in vivo. Collectively, our findings suggest that nerandomilast attenuates fibrotic remodeling while modulating alveolar epithelial cell state dynamics, which may provide a possible cellular explanation for its clinical efficacy in patients with pulmonary fibrosis.
PubMed2026
Persisting Region-Specific Microglia Activation and Synaptic Imbalance During Remission in a DSS-Induced Colitis Model.
Ulcerative colitis (UC) patients experience cycles of active gut inflammation and remission, with neuropsychiatric comorbidities persisting even during clinical remission. While the dextran sulfate sodium (DSS) mouse model was previously applied to study gut-brain interactions, those studies focused on acute protocols missing the chronic, relapsing-remitting nature of human UC, when patients continue to experience central nervous system symptoms. Thus, we employed a chronic DSS treatment regimen comprising three cycles of active intestinal inflammation followed by remission phases to investigate region-specific microglial dynamics and their functional consequences on neuronal synapses. Transient blood-brain barrier alteration was detected during active chronic inflammation that was resolved during remission. Cortical microglia exhibited sustained iNOS-enriched activation state during remission, which coincided with synaptic imbalance: VGLUT1+ glutamatergic synaptosomes increased significantly in remission, while VGAT+ GABAergic vesicles declined, alongside suppressed neuronal c-fos expression. Hippocampal microglia adopted an ARG1-dominant phenotype with enriched TREM2, P2Y12R, and F4/80 expression during remission, indicating a phagocytic, reparative state. Hippocampal synaptosome analysis revealed selective excitatory enhancement with preserved inhibitory markers. Morphological analysis confirmed region-specific remodeling: cortical microglia displayed delayed process elaboration during remission, while hippocampal responses varied from transient (CA1) to persistent (CA3) somatic hypertrophy. These findings establish that remission from peripheral inflammation does not fully restore brain immune homeostasis. Persistent, region-specific microglial reactivity with cortical pro-inflammatory states associated with synaptic dysfunction and hippocampal adaptive responses preserving circuit integrity provides a mechanistic understanding for neuropsychiatric comorbidities in UC and suggests that brain-targeted therapies may be required to address the full disease burden.
PubMed2026
Platycodon grandiflorus decoction against lipopolysaccharide (LPS)-induced acute lung injury via Keap1/Nrf2/ARE signaling pathway.
BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe inflammatory disease with high incidence and mortality rates. The traditional Chinese medicine Platycodon grandiflorus decoction (PGD) exerts protective effects against lipopolysaccharide (LPS)-induced ALI via the PI3K/AKT/NF-κB pathway, but its underlying molecular mechanisms require further elucidation. OBJECTIVES: This study aimed to investigate the molecular mechanism underlying the protective effects of PGD against LPS-induced ALI. METHODS: In-vivo experiments employed an LPS-induced ALI mouse model to assess PGD's therapeutic potential. Complementary in-vitro studies examined the molecular mechanisms of PGD-enriched serum using human pulmonary epithelial (A549) and microvascular endothelial (HPMEC) cell lines. Nrf2 involvement in PGD-mediated protection was verified through siRNA-mediated gene silencing and subsequent functional validation. RESULTS: Both in-vitro and in vivo analyses demonstrated that PGD effectively protects pulmonary tissues from LPS-induced damage. PGD administration notably enhanced Nrf2 nuclear translocation and decreased Keap1 expression at the protein and transcriptional levels, while promoting the expression of HO-1 and NQO1 biomarkers. Notably, Nrf2 gene silencing abolished PGD's therapeutic effects, including its anti-apoptotic properties. CONCLUSIONS: PGD's therapeutic efficacy in LPS-induced ALI is mediated through modulation of the Keap1/Nrf2/ARE signaling pathway.
PubMed2026
Probiotic Intervention With Bacillus coagulans and Lactobacillus acidophilus in Small Animals Experimental Ulcerative Colitis: Insights From a Small Animal Model.
Inflammatory bowel disease is a significant health concern not only in humans but also in companion animals and livestock, where it manifests as chronic diarrhoea, abdominal pain, and mucosal injury. Probiotics have gained increasing attention as potential therapeutic agents due to their immunomodulatory effects and ability to restore intestinal homeostasis. This study investigated the therapeutic efficacy of Bacillus coagulans and Lactobacillus acidophilus in an acetic acid-induced ulcerative colitis model in Wistar rats. Forty male rats were randomly assigned to control, colitis, mesalazine, B. coagulans, and L. acidophilus treatment groups. Disease severity was evaluated by macroscopic and histopathological scoring, colon length and weight, pro-inflammatory cytokine levels (IL-1β, IL-17), and inflammasome-associated gene expression (NLRP3, Caspase-1, IL-18, TNF-α). The results showed that colitis induction significantly increased pro-inflammatory cytokine expression and histological damage compared with controls. Both probiotics markedly reduced inflammatory markers, improved colon morphology, and attenuated inflammasome activation. Their protective effects were comparable to mesalazine, the standard treatment. These findings suggest that B. coagulans and L. acidophilus can serve as effective adjunct therapies for ulcerative colitis in veterinary practice, with potential translational applications for companion animals and livestock.
PubMed2026
Protective effects of Xiaoshi Lipi formula on gastric precancerous lesions via multi-target regulation of inflammation, oxidative stress, ferroptosis and apoptosis.
BACKGROUND: Xiaoshi Lipi formula, a traditional Chinese medicine, may alleviate Gastric precancerous lesion (GPL) progression through multi-target mechanisms. OBJECTIVES: To evaluate the protective effects of Xiaoshi Lipi formula on GPL and its underlying mechanisms. METHODS: GPL was induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine and sodium deoxycholate. Animals were assigned to normal, model, positive control and low-, medium-, or high-dose Xiaoshi Lipi formula groups. Gastric pathology was assessed by HE and AB-PAS staining. Serum inflammatory cytokines (TNF-α, IL-6, IL-1β), gastric function markers (G-17, PG I, PG II, PGE2), oxidative stress indices (ROS, MDA, SOD, GSH), ferroptosis- and antioxidant-related proteins and apoptosis (TUNEL) were analyzed. RESULTS: Xiaoshi Lipi formula markedly alleviated gastric mucosal atrophy and intestinal metaplasia and improved gastric function. In the medium-dose group, G-17, PG I and PGE2 increased by ~90%, 70% and 62%, respectively, while PGⅡ decreased by ~40%. TNF-α, IL-6 and IL-1β were reduced by ~45%. ROS and MDA declined by ~48% and 50%, while SOD and GSH rose by ~38% and 83%. GPX4 and SLC7A11 were restored, Nrf2/HO-1 pathway activated and TUNEL-positive cells reduced by ~68%. Medium-dose effects were comparable to the positive control. CONCLUSION: Xiaoshi Lipi formula ameliorates GPL by targeting inflammation, oxidative stress and ferroptosis, supporting its potential in gastric cancer prevention.
PubMed2026
TGα2β-modified adipose-derived stem cell exosomes regulate collagen synthesis in fibroblasts and enhance chronic ulcerative wound repair through the ILK/AKT signaling pathway.
BACKGROUND: Chronic ulcerative wounds, particularly diabetic foot ulcers, present a significant clinical challenge owing to their complex pathophysiology and limited response to conventional therapies. Although exosomes derived from adipose-derived mesenchymal stem cells (ADSC-exos) have shown promise in promoting tissue repair, the specific mechanisms underlying their effects, particularly their involvement in the integrin-linked kinase (ILK)/AKT signaling pathway, remain poorly elucidated. OBJECTIVES: This study aimed to elucidate whether exosomes from ADSCs modified with ITGα2β (ITGα2β-ADSC-exos) enhance chronic ulcerative wound healing by modulating fibroblast collagen synthesis via the ILK/AKT signaling axis. METHODS: ITGα2β-ADSC-exos were characterized using transmission electron microscopy, nanoparticle tracking analysis and Western blotting. Their effects on ILK/AKT pathway activation, migration and collagen production in fibroblasts were assessed in-vitro. For in-vivo validation, a diabetic rat model with full-thickness skin wounds was established and randomly allocated into five groups: Control (PBS), unmodified exosomes, ITGα2β-Modified exosomes (ITG-Exo), ITG-Exo co-administered with the ILK inhibitor QLT0267 and ITG-Exo co-administered with the AKT inhibitor MK-2206. Wound healing progression, histological changes, microvessel density (via CD31 immunohistochemistry) and the expression of pathway-related proteins (p-AKT, COL1A1, COL3A1) were evaluated. RESULTS: ITGα2β modification enhanced the levels of characteristic markers and the yield of ADSC-exos. These modified exosomes potently activated the ILK/AKT pathway in fibroblasts, subsequently promoting fibroblast proliferation, migration and the synthesis of type I and III collagen. In diabetic rats, ITGα2β-ADSC-exos significantly accelerated wound closure, improved granulation tissue formation and increased microvessel density. Crucially, these therapeutic effects were entirely abrogated by co-administration of either the ILK inhibitor QLT0267 or the AKT inhibitor MK-2206, which instead exacerbated tissue vacuolization and inflammation. Western blot analysis confirmed that the pro-healing effects correlated with upregulation of p-AKT and collagen proteins. CONCLUSION: ITGα2β-modified ADSC-exos regulate collagen synthesis in fibroblasts and facilitate chronic ulcerative wound healing via the ILK/AKT signaling pathway.