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关键词： Curcumin   Cartilage endplate   Apoptosis   IL-1 beta   Intervertebral disc degeneration  

摘要： The study aims to investigate the protective effect of curcumin on intervertebral disc degeneration by examining its influence on IL-1 beta-induced apoptosis in rat cartilage endplate cells. The rat primary chondrocytes treated by IL-1 beta at 10 ng /mL was utilized as a rat model in intervertebral disc degeneration, followed by incubation with different concentration of curcumin (10, 15, 20 mu mol/L). Cell apoptosis and cell proliferation were conducted through flow cytometry and CCK-8, respectively. Furthermore, immunofluorescence staining was used to visualize the expression of Bax and Bcl-2 inside the cells. Western blotting was performed to determine the expression of the Bax and Bcl-2. Curcumin promoted proliferation of chondrocytes treated by IL-1 beta, but inhibited the apoptosis. Importantly, curcumin significantly downregulated the expression level of Bax but upregulated the expression level of Bcl-2. Strengths of this study include the use of multiple assays to validate the findings, while limitations include the in vitro nature and lack of in vivo data. Curcumin is capable of ameliorating IL-1 beta -induced intervertebral disc degeneration by Bcl-1 and Bax production. This study provides a foundation for future research into curcumin's therapeutic potential in intervertebral disc degeneration.

关键词： immune escape   HLA   tumor microenvironment   tumor evolution   precancer   immunotherapy resistance  

摘要： Genetic immune escape (GIE) alterations pose a significant challenge in cancer by enabling tumors to evade immune detection. These alterations, which can vary significantly across cancer types, may often arise early in clonal evolution and contribute to malignant transformation. As tumors evolve, GIE alterations are positively selected, allowing immune-resistant clones to proliferate. In addition to genetic changes, the tumor microenvironment (TME) and non-genetic factors such as inflammation, smoking, and environmental exposures play crucial roles in promoting immune evasion. Understanding the timing and mechanisms of GIE, alongside microenvironmental influences, is crucial for improving early detection and developing more effective therapeutic interventions. This review highlights the implications of GIE in cancer development and immunotherapy resistance, and emphasizes the need for integrative approaches.

关键词： Cardiovascular diseases   Cardiovascular disease risk   Cancer risk factors   Cardiovascular therapy   Psoriasis   Medical risk factors   Type 2 diabetes risk   Epidemiology  

摘要： Background Psoriasis is associated with various cardiovascular diseases (CVDs). The aim of this study was to compare the risk of CVD in patients with psoriasis who were prescribed biologics or oral therapies, and to assess the association between different classes of biologics and CVD risk. Methods and Findings This retrospective cohort study utilized the TriNetX Global Collaborative Network (2014-2025). Patients with psoriasis newly prescribed biologics (BIO-cohort) and those newly initiating oral anti-psoriatic drugs without biologic exposure (Non-BIO-cohort) were enrolled. A propensity score-matched analysis was conducted, accounting for age, sex, race, comorbidities, body mass index, serum lipid profile, and inflammatory marker levels. Cardiovascular risk was compared between the BIO- and Non-BIO-cohorts using Cox regression to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). After matching, each cohort comprised 12,732 patients, with approximately 50% being female, a mean age of 57 years, and 55% identifying as White. The 5-year cumulative incidence of any CVDs was significantly lower in the BIO-cohort (10.68%;95% CI [10.03%, 11.36%]) than in the Non-BIO-cohort (16.17%;95% CI: [15.34%, 17.05%]) (p < 0.001). The BIO-cohort had attenuated risks of any CVDs (HR 0.621;95% CI [0.571, 0.676]), cerebrovascular diseases (HR 0.616;95% CI [0.519, 0.731]), arrhythmias (HR 0.632;95% CI [0.565, 0.706]), inflammatory heart diseases (HR 0.566;95% CI [0.360, 0.891]), ischemic heart diseases (HR 0.579;95% CI [0.465, 0.721]), heart failure (HR 0.637;95% CI [0.521, 0.780]), non-ischemic cardiomyopathy (HR 0.654;95% CI [0.466, 0.918]), thrombotic disorders (HR 0.570;95% CI [0.444, 0.733]), peripheral arterial occlusive diseases (HR 0.501;95% CI [0.383, 0.656]), and major adverse cardiac events (HR 0.697;95% CI [0.614, 0.792]). Receiving only anti-tumor necrosis factor (TNF)-alpha (HR 0.886;95% CI [0.807, 0.973]), anti-interleukin (IL)-17 (HR 0.724;95% CI [0.599,

关键词： HLA-C*06:395   next-generation sequencing   novel allele  

摘要： HLA-C*06:395 differs from HLA-C*06:02:01:01 by a single nucleotide substitution at position 520 G>A.

关键词： genome-wide association study   HLA-DQB1   oral squamous cell carcinoma   susceptibility   young age  

摘要： IntroductionEnvironmental exposure to carcinogens causes mucosal damage in the upper aerodigestive tract and can lead to cancers. The susceptibility to carcinogens varies between individuals. To identify susceptibility genes in head and neck cancers, we enrolled patients with early-onset disease and analyzed them by genome-wide association study. Methods and MaterialsThis case-control study included 54 young male patients with oral squamous cell carcinoma (OSCC) who were treated between March 1996 and December 2016, as well as 2400 healthy controls. A single nucleotide polymorphism (SNP) array was used to determine genetic loci that increase susceptibility to OSCC. In another validation cohort, sequencing-based typing (TBG Biotechnology Corp., Taipei, Taiwan) was used to determine the HLA-DQB1 genotype in another 100 OSCC patients. ResultsWe analyzed the allele frequencies of 664,994 autosomal SNPs in 54 OSCC cases. In a genome-wide association analysis, four SNPs on chromosomes 6, 7, 9, and 12 were significantly different between OSCC patients and controls (corrected p < 1.0 x 10-6). HLA-DQB1 was closest to rs28451423 on chromosome 6. In the validation cohort, HLA-DQB1*05:02 in OSCC (18.5%) was significantly different from the normal population (7.0%) (p = 0.009). The influence of disease onset was independently significant after adjusting smoking, alcohol drinking, and areca-quid chewing (p = 0.015, OR: 3.922, 95% confidence interval: 1.311-11.734). Furthermore, HLA-DQB1*05:02 was associated with early-onset OSCC (p = 0.004). ConclusionHLA-DQB1*05:02 increases individuals' risks of OSCC independent of environmental exposures, particularly in cases of early-onset OSCC. This study provides a genetic basis and disease marker for personalized prevention of OSCC.

关键词： Early BPA exposure   Anxiety   Neuroinflammation   Juvenile and adult ages   Pyroptosis   NF-B-k/IL-1 beta/NLRP3/Caspase-1 pathway  

摘要： Bisphenol A (BPA), a common endocrine-disrupting chemical, is found in a wide range of home plastics. Early-life BPA exposure has been linked to neurodevelopmental disorders;however, the link between neuroinflammation, pyroptosis, and the development of psychiatric disorders is rarely studied. The current study attempted to investigate the toxic effect of BPA on inflammatory and microglial activation markers, as well as behavioral responses, in the brains of male rats in a dose- and age-dependent manner. Early BPA exposure began on postnatal day (PND) 18 at dosages of 50 and 125 mg/kg/day. We started with a battery of behavioral activities, including open field, elevated plus- and Y-maze tests, performed on young PND 60 rats and adult PND 95 rats. BPA causes anxiogenic-related behaviors, as well as cognitive and memory deficits. The in vivo and in silico analyses revealed for the first time that BPA is a substantial activator of nuclear factor kappa B (NF-kappa B), interleukin (IL)-1 beta, -2, -12, cyclooxygenase-2, and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, with higher beclin-1 and LC3B levels in BPA rats' PFC and hippocampus. Furthermore, BPA increased the co-localization of caspase-1 immunoreactive neurons, as well as unique neurodegenerative histopathological hallmarks. In conclusion, our results support the hypothesis that neuroinflammation and microglial activation are involved with changes in the brain after postnatal BPA exposure and that these alterations may be linked to the development of psychiatric conditions later in life. Collectively, our findings indicate that BPA triggers anxiety-like behaviors and pyroptotic death of nerve cells via the NF-kappa B/IL-1 beta/NLRP3/Caspase-1 pathway.

关键词： HLA-B   HLA-B*07:528   NGS   novel HLA allele  

摘要： HLA-B*07:528 differs from HLA-B*07:02:01:26 by one nucleotide substitution in codon 286 (GGC>GAC) in exon 5.