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关键词： Diabetes   Wound healing   Dermal matrix   Hydrogel   VEGF   IL-10   Microspheres  

摘要： Diabetic wounds are among the most common and costly complications in diabetic patients. As a result, numerous studies have been conducted to explore effective approaches for accelerating the wound healing process. Biological hydrogels are frequently used for wound healing due to their favorable properties compared to other materials. In this study, we evaluated the effect of a bioactive and degradable hydrogel based on dermal matrix (HDM) encapsulated with microspheres containing vascular endothelial growth factor (VEGF) and interleukin (IL)-10 on promoting wound healing in diabetic rats. Forty-five diabetic rats were randomly assigned to three groups (n = 15): control, HDM, and HDM encapsulated with microspheres containing VEGF and IL-10 (HDMM). In addition, non-diabetic untreated rats (healthy group) were considered as control (n = 15). Wound assessments were performed on days 7, 14, and 21. The results demonstrated significant improvements in wound closure rate, fibroblast and blood vessel counts, collagen density, concentration levels of TGF-b and VEGF cytokines, and biomechanical parameters in the treatment groups compared to the control group, with the most pronounced effects observed in the HDMM group. Additionally, the HDMM group exhibited a greater reduction in neutrophil and macrophage counts, as well as decreased levels of TNF-a and IL-1b cytokines compared to the other groups. In conclusion, the HDM loaded with microspheres containing VEGF and IL-10 showed a more significant effect in promoting the healing of diabetic wounds. (c) 2025 The Author(s). Published by Elsevier BV on behalf of The Japanese Society for Regenerative Medicine. This is an open access article under the CC BY-NC-ND license (http://***/ licenses/by-nc-nd/4.0/).

关键词： biological DMARD   Pregnancy and reproduction   Infection  

关键词： Bladder cancer   Cytoskeleton reorganization   TNF-alpha   METTL3   CLASP2   IQGAP1  

摘要： Background: Bladder cancer (BCa) metastasis is a multi-step process triggered by cytoskeleton reorganization. However, the regulation mechanism of cytoskeleton reorganization in BCa remains ambiguous. This study elucidated the influence of tumor necrosis factor-alpha (TNF-alpha) in cytoskeleton remodeling during BCa metastasis and its possible mechanisms. Methods: Colony formation, scratch, transwell, and the nude mouse model were adopted to evaluate the growth and metastasis. Molecular expression was assessed by immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting. The N6-methyladenosine (m6A) level was detected by methylated RNA immunoprecipitation (MeRIP). Protein interaction was validated by Co-immunoprecipitation (Co-IP). Immunofluorescence staining was used to identify rearrangement of actin filament fibers (F-actin) and protein colocalization. Results: TNF-alpha facilitated cytoplasmic linker associated protein 2 (CLASP2) and methyltransferase like 3 (METTL3) expression in a dose (10-50 ng/mL)-dependent manner in BCa. CLASP2 high expression suggested a shorter overall survival of BCa patients. CLASP2 deficiency suppressed BCa cell proliferation, migration, and invasion via disrupting F-actin cytoskeleton. Mechanistically, TNF-alpha promoted METTL3-mediated m6A modification of CLASP2 to enhance CLASP2 mRNA stability. Moreover, CLASP2 directly interplayed with IQ motif containing GTPase activating protein 1 (IQGAP1) to regulate F-actin cytoskeleton remodeling. In vivo data demonstrated that inhibition of METTL3/CLASP2 axis delayed lung metastasis in nude mice. Conclusion: TNF-alpha favors BCa cell metastasis, which involves METTL3-mediated m6A modification of CLASP2 that interacts with IQGAP1, thus leading to F-actin cytoskeleton remodeling. Our findings suggest targeting TNF alpha/METTL3/CLASP2/IQGAP1 axis as a potential avenue for promising treatment for BCa.

关键词： Sarcopenia   Epidemiology   biological DMARD   Disease-modifying Drugs (DMARDs)  

摘要： Background: The Body composition of patients with spondyloarthritis (SpA) appears to differ from that of healthy adults [1]. However, distribution of fat and lean mass has important implications for health. Objectives: To compare prevalence of abnormal body composition phenotypes (sarcopenia, overfat, and sarcopenic obesity) in SpA patients with axial SpA (axSpA) or psoriatic arthritis (PsA), and to identify predictors of these conditions in those receiving conventional treatments (NSAIDs or csDMARDs) or Tumor-necrosis factor inhibitors (TNFi). Methods: Consecutive patients with SpA on either conventional treatments or TNFi underwent a standardized assessment that included patient and disease characteristics. Physical performance was assessed using the short physical performance battery (SPPB) and grip strength measurement. Body composition was assessed with dual-energy x-ray absorptiometry (DXA), which measured body fat and appendicular lean mass (ALM) index (ALMI). ALMI was classified as low if <7 for males and <5.5 for females. Obesity was defined by a DXA body fat percentage ≥30% (male) or ≥40% (female), while sarcopenia was determined by an ALM/BMI <0.789 (male) or <0.512 (female). The combination of sarcopenia and obesity was classified as sarcopenic obesity. Continuous and categorical measures of body composition were compared between patients with axSpA and PsA, stratified by sex according to treatment regimen. Results: A total of 140 axSpA and 73 PsA patients were recruited (Table 1). Compared to PsA, axSpA patients were younger but had a longer disease duration, were more frequently treated with TNFi, and less often with csDMARDs. Male patients on TNFi were more likely to have a diagnosis of axSpA, had lower patient global assessment scores, and were less often obese than male patients on conventional treatment (Table 2). The prevalence of sarcopenia and sarcopenic obesity was significantly higher in men receiving TNFi compared to male patients on conventi

关键词： Anti-IL-23   Biologics   Psoriasis   Real-Life   Tildrakizumab  

摘要： IntroductionTildrakizumab is a monoclonal antibody targeting interleukin (IL)-23 approved for the treatment of moderate-to-severe plaque psoriasis across two different dosages (100 mg and 200 mg). The higher dosage is recommended for patients with a body weight >= 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] >= 16 or the involvement of difficult-to-treat areas). We conducted a 52-week multicenter retrospective study to compare the effectiveness and safety of both dosages and assess their impact on specific patient *** enrolled a total of 540 patients with high disease burden or body weight >= 90 kg;177 and 363 were treated with tildrakizumab 200 mg and 100 mg, respectively. The effectiveness was evaluated in terms of PASI 90, PASI 100, and PASI <= 2 at weeks 16, 28, and 52. We also performed subanalyses according to the body weight (>= 90 kg), PASI >= 16, prior biologic exposure, involvement of difficult-to-treat areas, and the presence of at least one cardiometabolic *** 16 weeks of treatment, a higher proportion of patients in the 200-mg group achieved PASI 90 and PASI 100 compared to those in the 100-mg group (43.5% vs. 34.3% and 36.4% vs. 24.2%, respectively). These results were sustained at 1 year, with PASI 90 and PASI 100 reached by 68.6% and 52.9% of patients in the 200-mg group, respectively, versus 57.3% and 35% in the 100-mg group. All subgroup analyses consistently indicated a trend toward greater effectiveness with tildrakizumab 200 mg, particularly in terms of PASI 90 and PASI 100 achievement at weeks 16 and 52. No differences in the safety profile were observed throughout the study *** findings confirm the superior effectiveness of tildrakizumab 200 mg over 100 mg in specific subgroups of patients with a comparable safety profile across the study period.

关键词： Thioacetamide   Ginkgo-biloba   dandelion   antioxidant   apoptosis  

摘要： Liver injuries, especially those induced by chemical toxins and pharmaceuticals, are increasingly prevalent. This study evaluated the hepatoprotective effects of Ginkgo biloba and dandelion extracts in a rat model of thioacetamide (TAA)-induced liver injury. Twenty-eight male albino rats were randomly assigned to four groups: control, TAA-treated, TAA plus G. biloba (100 mg/kg), and TAA plus dandelion (500 mg/kg). TAA administration over eight weeks significantly elevated serum liver enzymes (AST, ALT, ALP, and GGT), bilirubin, cholesterol, and triglycerides (P < 0.05) while significantly reducing total protein and albumin levels (P < 0.05). TAA also induced oxidative stress, evident by increased hepatic malondialdehyde and reduced glutathione levels (P < 0.05). Co-treatment with G. biloba or dandelion extracts significantly ameliorated these biochemical alterations (P < 0.05), with G. biloba demonstrating slightly stronger effects. Histopathological examination showed reduced necrosis, fibrosis, and inflammatory cell infiltration in treated groups. Immunohistochemical analysis confirmed decreased expression of TNF-alpha and P53 proteins (P < 0.05), indicating anti-inflammatory and anti-apoptotic properties. These findings suggest that G. biloba and dandelion extracts confer protective effects against TAA-induced liver damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

关键词： DNA sequence analysis   HLA-A   new allele   next-generation sequencing   single nucleotide polymorphism  

摘要： The novel HLA-A*03:01:133 allele differs from A*03:01:01:01 by a change of C -> T in exon 4.

关键词： limbal stem cell deficiency   cornea   epithelium   macrophages   monocytes   inflammation   TNF-alpha   therapy  

摘要： Purpose: Ocular chemical injuries often cause uveal inflammation, upregulation of TNF-alpha at the limbus, and subsequent limbal stem cell (LSC) damage. In this study, we investigate the protective role of TNF-alpha suppression in LSC survival. Methods: Corneal alkali injuries were performed using NaOH as previously described by our group. Anterior chamber pH elevation in the absence of corneal alkali exposure was achieved by cannulation. A CX3CR1(+/EGFP)::CCR2(+/RFP) bone marrow chimera was used to study the role of innate immune cells in LSC damage, which was assessed by TUNEL assay, ABCB5, cytokeratin 12 and 13 staining, flow cytometry, in situ hybridization, and qPCR. Corneal neovascularization and conjunctivalization were evaluated by light microscopy. Intraperitoneal injection of 6.25 mg/kg infliximab was administered after irrigation. A TNFR1/2 knockout mouse was used to confirm the findings by a second method. Results: Systemic administration of 6.25 mg/kg infliximab suppressed uveal inflammation after anterior chamber pH elevation or corneal alkali injury and led to reduction of TNF-alpha secreting CCR2(+) and CX3CR1(+) monocytes in the basal limbal tissue. In turn, this led to LSC survival (P < 0.01) and allowed reestablishment of K12(+) epithelium (P < 0.05) on the injured cornea. Moreover, it led to less corneal neovascularization, conjunctivalization, and scarring, as compared with untreated animals. The protective effect of TNF-alpha suppression was confirmed in TNFR1/2 knockout mice. Conclusions: Prompt systemic administration of TNF-alpha inhibitor prevents LSC deficiency and facilitates corneal reepithelialization after alkali burn. TNF-alpha suppression may benefit the outcomes of other ocular injuries that cause LSC deficiency.

关键词： HBV reactivation   rheumatologic patients   TNF-alpha inhibitor potency  

摘要： BackgroundRheumatologic patients who test positive for hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) are at risk of HBV reactivation when treated with TNF-alpha inhibitors. The effect of TNF-alpha inhibitor potency on this risk remains unclear, despite guidelines advising potency-based risk stratification. This study examines how TNF-alpha inhibitor potency influences the risk of HBV *** January 2008 to June 2023, 711 new TNF-alpha inhibitor users with rheumatic diseases were identified, including 39 HBsAg+ patients with antiviral prophylaxis, 72 HBsAg+ patients without antiviral prophylaxis, and 600 HBsAg-/HBcAb+ patients without prophylaxis. A Cox proportional hazards model assessed factors associated with HBV *** 2526 person-years of follow-up, HBsAg+ patients without antiviral prophylaxis had the highest HBV reactivation rate at 104.1 per 1000 person-years, followed by HBsAg-/HBcAb+ patients at 12.9, and HBsAg+ patients with antiviral prophylaxis at 12.6 per 1000 person-years. Multivariate Cox regression revealed that high-potency TNF-alpha inhibitors significantly increased HBV reactivation risk in HBsAg+ patients without antiviral prophylaxis (aHR 3.24, 95% CI: 1.09-9.67, p = 0.04). Adalimumab had a higher reactivation risk compared to etanercept (aHR 3.23, 95% CI: 1.02-10.17, p = 0.04), followed by golimumab (aHR 3.27, 95% CI: 0.91-11.64, p = 0.07). For HBsAg-/HBcAb+ patients, TNF-alpha inhibitor potency did not significantly impact HBV reactivation risk;instead, age over 65 was the only significant risk factor (aHR 3.37, 95% CI: 1.30-8.70, p = 0.01).ConclusionHigh-potency TNF-alpha inhibitors significantly increase HBV reactivation risk in HBsAg+ patients, while HBsAg-/HBcAb+ patients have a uniformly low risk across all inhibitors.