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关键词： Coixol   Ulcerative colitis   IL17A signaling pathway   Mitophagy   Inflammation   Molecular docking  

摘要： Coicis Semen, a versatile food known for its nutraceutical properties, is valued for its edibility. Coixol, the principal bioactive component of Coicis Semen, exhibits potent anti-inflammatory effects, highlighting its potential in managing inflammatory diseases. This study investigates the efficacy of Coixol in alleviating ulcerative colitis (UC) and describes its underlying mechanisms. By integrating network pharmacology with transcriptome profiling, we demonstrate that Coixol modulates genes involved in interleukin (IL)17 A signaling pathway and autophagy. We also predict the binding potential of Coixol and its target proteins using molecular docking. We found that Coixol notably reduced weight loss, colonic injury, inflammatory cytokines, and mitochondrial damage in dextran sulfate sodium (DSS)-induced mice. Moreover, Coixol greatly inhibited the IL17A signaling pathway and boosted mitophagy-related gene and protein expressions in both DSS-induced mice and IL17Astimulated RAW264.7 cells. Molecular docking further revealed Coixol's ability to bind tightly and stably to IL17A, IL17RA, TNF receptor-associated factor 6 (TRAF6), nuclear factor kappa-B (NF-kappa B), and Inhibitor of Nuclear Factor kappa B alpha (IKB alpha). Taken together, these data suggest that Coixol's therapeutic potential in UC is mediated by its inhibition of the IL17A signaling pathway and interactions with relevant targets, thus promoting mitophagy. This positions Coixol as a functional food candidate for managing UC.

关键词： HLA   Haploidentical stem cell transplant   Donor-specific antibodies   Graft failure   Reduced-intensity conditioning  

摘要： Background: Donor-specific (DSA) anti-HLA antibodies can adversely influence outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Methods: Patients who received a haplo-HSCT from a sibling after reduced-intensity conditioning (RIC) and had a virtual cross match against donor's HLA typing performed and a positive single-antigen microspherebased immunoassay test were studied. DSA were considered positive with a mean fluorescence intensity (MFI) >= 1000. Results: Anti-HLA DSA >= 1000, median 2623 (range 1000-13,235) MFI were documented in 27/65 (42 %) patients. In 14 (21.5 %) patients, antibodies were anti-HLA class I, in 18 (27.7 %) anti-HLA class II, and in 6 (9.2 %) against both. Overall (OS) and event-free survival (EFS) were lower in patients with anti-HLA Class I DSA (p = 0.026 and p = 0.037, respectively). One-year mortality was higher with anti-HLA DSA of any class (p = 0.009). Nine (64.3 %) of 14 patients with DSA anti-HLA class I died, vs. 11/18 (61 %) with class II DSA (p = 0.238). Anti-HLA DSA were not associated with graft failure (GF) in the cohort. There was no difference in relapse or acute or chronic GVHD in patients with and without DSA. Conclusion: Anti-HLA Class I DSA > 1000 MFI after haplo-HSCT was associated with lower OS and EFS and higher one-year mortality, but no with GF, acute or chronic GVHD, or relapse.

关键词： rheumatoid arthritis   influenza   vaccine   bDMARDs  

摘要： Objectives The objectives of this study were to evaluate the effectiveness of short message service (SMS) and/or email reminders in improving influenza vaccination coverage rates among RA patients treated with anti-TNF therapies, and to identify factors associated with *** This study was a nested randomized controlled trial in the ART e-cohort, an ongoing French nationwide multicentre prospective cohort of RA patients treated with anti-TNF therapy. Patients were 1:1 randomized, with stratification on age. The intervention consisted of regular reminders via SMS and/or emails to get vaccinated against influenza during the vaccination campaign. At the end, all participants received a questionnaire. The primary outcome was influenza vaccination coverage. Secondary outcomes included the vaccination coverage before and after the COVID-19 pandemic, and factors associated with *** Between October 2021 and April 2022, 446 participants were randomized (224 to the intervention group and 222 to the control group). Among them, 325 (73%) reported their vaccination status and 221 (68%) were vaccinated against influenza: 116/158 (73%) in the intervention group, vs 105/167 (63%) in the control group (relative risk 1.08;95% CI 0.95-1.23). The vaccination coverage before and after the COVID-19 pandemic did not differ (72% vs 72%;95% CI -8% to 8%). Age >= 65 years [odds ratio (OR) 6.25;95% CI 2.88-13.60] and previous influenza vaccination in the years before inclusion (OR 7.81;95% CI 4.36-14.02) were associated with higher rates of vaccinationConclusion SMS and/or e-mail reminders did not significantly improve influenza vaccination rates in our cohort. The COVID-19 pandemic did not substantially impact the influenza vaccination coverage. Our results might be counterbalanced by an already high vaccination *** registration ***, http://***, NCT05220423, NCT03062865.

关键词： HLA   HLA-B*54:21   novel allele   sequence-based typing   Taiwanese  

摘要： One nucleotide mutation in exon 2 of HLA-B*54:01:01:01 results in the novel allele, HLA-B*54:21.

关键词： Caspase-1   free androgen index   HDL   HOMA-IR   IL-10   LDL   PCOS   total cholesterol   triglycerides   and MDA  

摘要： Introduction:Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by hyperandrogenism, insulin resistance, and dyslipidemia. Inflammation and oxidative stress play critical roles in its pathogenesis. This observational cross-sectional study evaluated the relationship between serum Caspase-1, interleukin-10 (IL-10), homeostatic model assessment of insulin resistance (HOMA-IR), free androgen index (FAI), lipid profiles, and oxidative stress markers in women with *** and Methods:A total of 150 women diagnosed with PCOS participated in this study. Serum levels of Caspase-1, IL-10, HOMA-IR, FAI, lipid profiles (total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides), malondialdehyde (MDA), and superoxide dismutase (SOD) were ***:The results revealed significant elevations in Caspase-1, HOMA-IR, and lipid profiles, while IL-10 levels were lower compared to normal populations. Additionally, oxidative stress markers, including MDA, were significantly increased, while SOD levels showed a decline. Positive correlations were observed between Caspase-1, HOMA-IR, dyslipidemia, and oxidative stress ***:These findings suggest a crucial link between inflammation, insulin resistance, and oxidative stress in PCOS, contributing to its complex pathophysiology.

关键词： gut microbiota   IL-17 signaling pathway   moxibustion   network pharmacology   premature ovarian insufficiency   transcriptome  

摘要： ProblemPremature ovarian insufficiency (POI) is a significant cause of female infertility, severely impacting physical and mental health. Current treatments, primarily hormone replacement therapy, fail to restore ovarian function and may cause adverse effects. Moxibustion, a traditional Chinese medicine therapy, has shown potential in treating POI, but its mechanisms remain unclear. This study investigated the therapeutic effects of moxibustion on POI rats and explored its underlying *** of StudyA POI rat model was established using cyclophosphamide, and moxibustion was applied daily to the CV4 and SP6 acupoints for 4 weeks. We analyzed hormone levels, estrous cycles, follicle count, and gut microbiota. Transcriptomic and metagenomic sequencing were performed to identify potential pathways. Network pharmacology was used to predict active components and *** restored estrous cycles, improved hormonal imbalances, and increased ovarian reserve function. Network pharmacology identified five active components in moxa, and based on the results of network pharmacology and transcriptome sequencing, we believe that the regulation of the IL-17 pathway is the key mechanism. Further experiments showed moxibustion downregulated the Th17/IL-17 pathway, reduced key proteins such as IL-17R, NF-kappa B, MMP3, I kappa B alpha, IL-1 beta, MMP9, TRAF6, and Cox2. Flow cytometry confirmed a decrease in Th17 cell proportion. Gut microbiota analysis revealed that moxibustion enhanced microbial diversity and modulated specific bacterial species, which correlated with improved hormone *** has a therapeutic effect on POI rats by regulating the Th17/IL17 pathway and gut microbiota, which provides evidence for the clinical application of moxibustion.

关键词： HLA   next-generation sequencing   novel allele  

摘要： HLA-C*08:272 differs from HLA-C*08:01:01:01 by one single nucleotide substitution at position 7 G>T in exon 1.