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关键词： Vitiligo   Peripheral blood mesenchymal stem cells   Melanocytes   Oxidative stress   Apoptosis  

摘要： Peripheral blood mesenchymal stem cells (PBMSCs) are a less invasive and more accessible source of adult multipotent stem cells than bone marrow mesenchymal stem cells (BMMSCs), because their collection does not involve anaesthesia and the risk of complications. In the present study, we observed that PBMSCs alone exhibited a higher concentration of IL-10 in the supernatant when cultured independently. Furthermore, the supernatant from the Transwell co-culture system of PBMSCs with H2O2-induced oxidative stress in B16 melanoma cells, which serves as an in vitro model for vitiligo, demonstrated elevated levels of IL-10. Western blot analysis revealed that the PI3K/AKT signaling pathway was activated in B16 melanoma cells, as evidenced by increased phosphorylation of AKT, enhanced expression of the antioxidant enzyme HO-1 and the anti-apoptotic protein Bcl-2, alongside decreased expression of the pro-apoptotic proteins Bax and Cleaved-Caspase 3. Notably, these effects were inhibited by the IL-10 neutralizing antibody (AB9969) and the PI3K inhibitor (LY294002). Collectively, our findings suggest that PBMSCs may mitigate oxidative damage and apoptosis in B16 melanoma cells through the paracrine activation of the PI3K/AKT signaling pathway by IL-10. This approach offers a novel, readily available, and minimally invasive cellular therapeutic strategy for vitiligo while also providing a theoretical basis for targeting antioxidant pathways in treatment.

关键词： pseudorabies virus   DNA polymerase processivity factor   pUL42   cGAS-STING   interferon  

摘要： Pseudorabies (PR), caused by the PR virus (PRV), is an acute infectious disease in livestock and various wild animals. PRV has developed several immune evasion mechanisms to antagonize the host's antiviral immune response. However, the precise role of PRV-encoded proteins in regulating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (IFN) gene (STING) signal for immune evasion remains unclear. In this study, we demonstrate that the PRV UL42 protein (pUL42) inhibited cGAS-mediated antiviral signaling by modulating cGAS recognition of dsDNA. Mechanistically, pUL42 interacts with the DNA-binding domain of cGAS, thereby inhibiting its recognition of double-stranded DNA, leading to the inhibition of its dimerization and oligomerization activation. Furthermore, knocking down the expression of the Ul42 gene in the PRV genome diminishes the antagonistic effect on type I IFN production and inhibits PRV replication. Ultimately, we have established that pUL42 targets cGAS-mediated signaling, thereby inhibiting the production of type I IFN and facilitating viral replication. Overall, our findings suggest that PRV pUL42 functions as an antagonist to evade the host's antiviral response by targeting the cGAS-STING *** GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) axis is essential for host resistance to DNA virus infections by regulating type I interferon production. However, whether pseudorabies virus (PRV) antagonizes the cGAS-STING signaling pathway to immune evasion is not fully investigated. In this study, we clearly demonstrated that the PRV pUL42 protein inhibits the recognition of double-stranded DNA of cGAS, leading to inhibiting the oligomerization and activation of cGAS, thereby suppressing the cGAS-mediated host antiviral immune responses. Taken together, our results reveal a novel strategy employed by PRV to evade host defenses, which will provide theoretical support for the development of anti-PRV drugs for the prevention

摘要： INTRODUCTION & OBJECTIVES: Renal cell carcinoma (RCC) represents the majority of kidney malignancies and is characterized by variable outcomes, even with current systemic therapies. Interleukin-6 (IL-6), a proinflammatory cytokine implicated in tumor progression and immune suppression, has been proposed as a prognostic biomarker in RCC. However, the evidence remains inconsistent due to methodological heterogeneity across studies. Therefore, our study aims to evaluate the prognostic significance of IL-6 in RCC by synthesizing data from published studies, specifically overall survival (OS) and progression-free survival (PFS). METHODS: A systematic meta-analysis was conducted to evaluate the prognostic significance of IL-6 in RCC. Eligible studies were identified through PubMed, ScienceDirect, and ProQuest up to March 2025. Inclusion criteria encompassed original articles measuring pre-treatment serum IL-6 levels in RCC patients and reporting associations with overall survival (OS) or progression-free survival (PFS). Random-effects models were used to compute pooled hazard ratios (HRs) and survival differences. RESULTS: Nine studies comprising 702 RCC patients were included. Patients with low IL-6 levels had significantly longer OS (difference: 5.36 months;95% CI: 2.2-8.53;p<0.001;I² = 0%) and PFS (difference: 6.41 months;95% CI: 1.3-11.53;p=0.01;I² = 48.5%) compared to those with high IL-6. The pooled HR for survival associated with elevated IL-6 was 2.06 (95% CI: -0.23-4.36), with considerable heterogeneity (I² = 89.19%) and borderline statistical significance (p=0.08). Despite variations in study design, sample size, and IL-6 detection methods, elevated IL-6 consistently predicted worse clinical outcomes. CONCLUSIONS: IL-6 is a promising prognostic biomarker in RCC, with elevated levels associated with significantly poorer OS and PFS.

关键词： Molluscs  

摘要： Marine food is well known to be rich in bioactive molecules that can aid in the prevention and treatment of chronic inflammatory diseases. Among them, bivalve mollusks such as the Pacific oyster (Crassostrea gigas) have been receiving growing interest due to their high nutritional and medicinal value. This study evaluated the chemical composition of Pacific oyster soft tissue extract (OE) and investigated its potential anti-inflammatory effects on human intestinal epithelial cells. The nutritional value including moisture, total protein, ash, total lipids, fatty acids (FAs), amino acids and minerals was analyzed, as well as polyphenol and carotenoid contents. The potential anti-inflammatory activity was tested at 5, 50, and 500 mu g mL-1 concentrations of OE against TNF-alpha induced inflammation in the intestinal human epithelial cell line Caco-2. OE was shown to reduce both the TNF-alpha induced activation of the NF-kappa B pathway and the alteration of the epithelial barrier integrity. The present findings might provide evidence for further understanding how whole dried oyster meat can be developed as a low-cost nutraceutical dietary supplement and thus can offer a natural alternative to alleviate intestinal inflammation associated with different chronic diseases.

关键词： Diabetes   Periodontitis   Scaling and root planing   Inflammatory cytokines   TNF-alpha   IL-1 beta   IL-10  

摘要： Objective: To evaluate the effect of scaling and root planing (SRP) on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of TNF-alpha, IL-1 beta, and IL-10 in periodontitis patients with and without diabetes. Methods: A cross-sectional study was conducted involving 76 patients diagnosed with periodontitis, including 38 with diabetes and 38 without diabetes. All participants received standardized SRP treatment. Periodontal clinical parameters and glycated hemoglobin (HbA1c) levels (in diabetic patients) were recorded at baseline and three months post-treatment. GCF samples were collected to assess concentrations of TNF-alpha, IL-1 beta, and IL-10 using ELISA. Changes in inflammatory cytokine levels were compared between the two groups before and after treatment. Results: SRP led to significant improvements in probing depth (PD), clinical attachment loss (CAL), bleeding index (BI), and plaque index (PLI) in both groups, with no significant intergroup differences. Diabetic patients showed a mean HbA1c reduction of 0.30 +/- 1.24%. TNF-alpha levels significantly decreased in both groups post-treatment (P < 0.001);however, post-treatment TNF-alpha levels remained significantly higher in the diabetes group than in the non-diabetes group (P < 0.001). No significant changes were observed in IL-1 beta levels in either group. IL-10 levels increased more in the non-diabetic group than in the diabetic group, though the difference was not statistically significant (P = 0.422). Conclusion: SRP treatment effectively improves periodontal clinical outcomes and modulates local inflammatory mediator levels. These findings highlight the need for individualized treatment strategies and interdisciplinary management in diabetic patients with periodontitis.

关键词： Plant extracts   Oxidative stress   IL-17 pathway   TGF-beta/Smad pathway   Photoaging  

摘要： BackgroundEucommia ulmoides Oliv. (PE), Styphnolobium japonicum (L.) Schott (PS) and Portulaca oleracea L. (PP) are well-characterized medicinal botanicals with established therapeutic profiles. PE exhibits anti-psoriatic and anti-aging properties through bioactive constituents, as demonstrated in vitro and in vivo research. PS flowers contain sophoricoside, a validated modulator of atopic dermatitis pathways, while PP displays broad-spectrum anti-inflammatory and antioxidant activities. Given their complementary mechanisms and the limited efficacy of single-agent approaches against UVB-driven oxidative stress/inflammation, we hypothesized that a tripartite extract (ESP: PE/PS/PP) would demonstrate synergistic photoprotection. This study evaluated the efficacy of ESP through integrated experimental cell models, a murine model of acute UVB-induced photoaging, and transcriptome *** extracts demonstrated synergistic antioxidant and photoprotective activities through multi-target mechanisms, effectively attenuating UVB-induced photoaging in vitro and in vivo. LC-QTOF-MS analysis identified major bioactive components comprising organic acids, polysaccharides, iridoids, and flavonoids. In a paracrine signaling model using conditioned medium from UVB-exposed HaCaT cells to stimulate HFF cells, ESP significantly inhibited UVB-induced secretion of inflammatory mediators (PGE2, TNF-alpha, IL-1 alpha, IL-6). Transcriptome sequencing coupled with RT-qPCR validation revealed that ESP attenuated photoaging via the IL-17 signaling pathway, downregulating key mediators including matrix metalloproteinases (MMP1/3/13), chemokines (CXCL3/8, CCL7), and colony-stimulating factors (CSF2/3). Furthermore, ESP reduced mitochondrial ROS generation, stabilized membrane potential, activated the TGF-beta/Smad pathway, and upregulated COL1A1 and COL3A1 expression. Significantly, in a murine model of acute UVB-induced photoaging, ESP treatment produced dose-dependent restoration o

关键词： Chlamydia pneumoniae   ER stress   IL-10   IRE1α   neutrophil  

摘要： Neutrophils are among the first cells to be recruited to the lungs during Chlamydia pneumoniae infection in mouse models;however, their regulatory functions are not yet fully understood. This study examined the mechanisms and significance of IL-10-producing neutrophils throughout C. pneumoniae pulmonary infection in C57BL/6 mice. Our findings revealed that infection with C. pneumoniae induces IL-10 secretion in bone marrow-derived neutrophils, depending on Toll-like receptor 2 (TLR2) activation. This process involves TLR2-dependent mitochondrial reactive oxygen species (ROS) production, which triggers the endoplasmic reticulum (ER) stress pathway, including IRE1α and subsequent Xbp1 splicing. Inhibition of this pathway or depletion of neutrophils (using the 1A8 monoclonal antibody) significantly reduces IL-10 levels in bronchoalveolar lavage fluid (BALF) in vivo. Conversely, the absence of IL-10-producing neutrophils, whether through depletion or TLR2 deficiency, leads to increased IL-12p70 and IFN-γ-positive NK cells, along with decreased regulatory T cells and M2-like macrophages. This results in a lower bacterial burden in the lungs but causes more severe pulmonary damage and decreased survival rates. These findings highlight that IL-10 produced by neutrophils via the TLR2-mitochondrial ROS-ER stress pathway is essential for modulating pulmonary immune responses and maintaining immune homeostasis during C. pneumoniae infection, thereby preventing excessive inflammation and tissue damage.

关键词： HLA-A*11:494   Indian   next-generation sequencing   novel allele  

摘要： The novel allele HLA-A*11:494 differs from HLA-A*11:01:01:01 by one non-synonymous substitution, c.G589A in Exon 3.

关键词： 胃癌   中医健脾养胃法   癌胚抗原   中医症候积分   临床疗效  

摘要： 研究中医健脾养胃法对胃癌患者癌胚抗原水平及中医症候积分等方面的调控效应。方法 本研究于2023年10月至2025年3月开展,将60例胃癌患者随机分组:参照组(30例)采用常规化疗,调研组(30例)在化疗基础上联合中医健脾养胃疗法,以比较两种方案的疗效差异。结果 疗效对比结果显示,调研组的综合临床疗效显著高于对照组(P<0.05)。在中医症候改善方面,两组治疗前评分相当(P>0.05),但治疗后调研组症候积分明显降低(P<0.05)。肿瘤标志物检测显示,两组在治疗前、后均未呈现统计学差异(P>0.05)。胃肠激素水平分析表明,虽然两组基线数据相近(P>0.05),但治疗后调研组胃肠激素水平提升更为显著(P<0.05)。结论 中医健脾养胃法联合化疗治疗胃癌效果显著,能更快改善临床症状,调节肿瘤标志物和胃肠激素水平,有效延缓疾病进展。

关键词： Azeri population   IL-10   IRF5   Palindromic rheumatism   PTPN22   Rheumatoid arthritis   Single-nucleotide polymorphisms   TNFAIP3  

摘要： ObjectivePalindromic rheumatism (PR) is characterized by frequent and irregular attacks of pain and swelling in the joints and peri-articular structures. In this study, we investigated TNFAIP3, PTPN22, IRF5, and IL-10 genes' single-nucleotide polymorphisms (SNPs) in patients with *** a cross-sectional study, patients with a diagnosis of PR and two control groups, including rheumatoid arthritis (RA) patients and healthy controls (HCs), were recruited. All participants were Azeri. The TNFAIP3 (rs2230926, rs5029937), PTPN22 (rs1217407, rs1217413), IRF5 (rs10954213, rs2004640), and IL-10 (rs1800872, rs1800896) gene SNPs were *** SNPs were genotyped in 25 PR patients, 41 RA patients, and 40 HCs. The TT genotype of TNFAIP3 rs2230926 and GG genotype of IL10 rs1800872 polymorphisms were less common in the PR group compared to the RA and HC groups. The C allele of TNFAIP3 rs2230926 polymorphism was more common in the PR group compared to the RA and HC groups. The TC genotype and C allele of IL10 rs1800896 and AG genotype of IRF5 rs10954213 polymorphisms were more common in the PR group compared to the HCs;however, there were no significant differences between the PR and RA groups. No significant difference was observed in the distribution of TNFAIP3 rs5025937, IRF5 rs2004640, PTPN22 rs1217413, and PTPN22 rs1217407 genotypes and alleles between the studied *** C allele of TNFAIP3 rs2230926, CC and TC genotypes and C allele of IL10 rs1800896, and AG genotype of IRF5 rs10954213 polymorphisms are associated with PR in the Azeri population. Key Points center dot The TT genotype of the TNFAIP3 rs2230926 polymorphism is less common in patients with palindromic rheumatism than in patients with rheumatoid arthritis and healthy *** dot The GG genotype of the IL10 rs1800872 polymorphism is less common in patients with palindromic rheumatism than in patients with rheumatoid arthritis and healthy *** dot The