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关键词： Human dermal fibroblasts   Methylnissolin-3-O-R-D -glucopyranoside   Tumor necrosis factor-alpha   Methylnissolin   Skin-aging  

摘要： Methylnissolin-3-O-R-D-glucopyranoside (MNG) and methylnissolin (MN) are pterocarpan derivatives that are found in plants, such as Astragalus membranaceus. There are limited existing studies on the potential health benefits of MNG, and currently there is no evidence to suggest that MNG has any impact on skin-aging. Tumor necrosis factor-alpha (TNF-alpha) plays a significant role in skin aging by promoting chronic inflammation, damaging skin cells, and impairing the skin's natural repair mechanisms. Targeting TNF-alpha or its downstream signaling pathways may be a promising strategy for preventing or reversing skin-aging. We tested the effect of MNG and MN on skin-aging by inducing cell inflammation and oxidative stress with TNF-alpha in HDFs. MNG and MN significantly reduced the TNF-alpha-induced secretion of matrix metalloproteinase-1 (MMP-1). However, MNG has more beneficial compound for oral administration than MN in pharmacokinetics analysis. The mechanism underlying the anti-skin-aging effect of MNG is related to the suppression of TNF-alpha-induced reactive oxygen species (ROS) generation and mitogen-activated protein kinase (MAPKs) phosphorylation. Our results suggest that MNG is a potential candidate for preventing skin-aging induced by TNF-alpha.

摘要： Activating mutations in STAT6 are common in Follicular Lymphoma (FL) and transformed FL and various other B cell lymphomas. Here, we report RNA-seq based gene expression data on normal human lymph node derived B lymphocytes (NBC;N = 6), and primary human FL WT (N = 11) or mutant (N = 4) for STAT6 before and after ex vivo stimulation with IL4. We found that STAT6 mutants result in broad based augmentation of IL4-induced gene expression. Unexpectedly, in FL with WT STAT6 we measured reduced baseline and IL4-induced gene expression levels when compared with NBC lymphocytes or FL with STAT6 mutations. We tracked the attenuated IL4/JAK/STAT6 response to co-existing CREBBP mutations and experimentally verified that intact CREBBP is required for the induction of many IL4-induced genes. One of the IL4-induced genes here identified is RRAGD, a small G-protein involved in lysosomal mTOR activation. We show that IL4 treatment induced RRAGD expression, that RRAGD is required for mTOR activation in lymphoma cells and that IL4-enhanced BCR signaling induced mTOR activation. The IL4 and BCR-induced mTOR activation was reduced by CREBBP mutants and augmented by mutant STAT6, establishing a link between STAT6 mutations and mTOR regulated pro-growth pathways in lymphoma.

关键词： HLA-C*03:595   new allele   NGS  

摘要： The novel HLA-C*03:595 allele was identified in an individual from the Sichuan province of China.

关键词： PLEK2   PDAC   Migration   Invasion   MMP1  

摘要： Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis primarily due to metastasis. Accumulating evidence suggests that PLEK2 acts as an oncogene in various tumors. This study aimed to investigate the effects of PLEK2 on PDAC. Expression analysis of PLEK2 was conducted using qRT-PCR, Western blot, and immunohistochemistry in PDAC. Wound healing and transwell assays were performed to evaluate the impact of PLEK2 on cell migration and invasion. A xenograft tumor model was employed to assess the in vivo proliferation of PLEK2. Additionally, the downstream pathway of PLEK2 was analyzed through RNA-seq and confirmed by Western blot analysis. The results demonstrated the upregulation of PLEK2 expression in tumor specimens. High PLEK2 expression was significantly associated with poor overall survival and advanced TNM stages. Correlation analyses revealed positive correlations between PLEK2 and TGF-beta, EGFR, and MMP1. Wound healing and transwell assays demonstrated that PLEK2 promoted PDAC cell migration and invasion, potentially through the activation of the epithelial-to-mesenchymal transition process. The in vivo experiment further confirmed that PLEK2 knockdown suppressed tumor growth. RNA-seq analysis revealed PLEK2's regulation of MMP1 and activation of p-ERK and p-STAT3, which were verified by Western blot analysis. Overall, the present study suggests that PLEK2 may play a tumor-promoting role in PDAC. These findings provide valuable insights into the molecular mechanisms of pancreatic cancer and highlight the potential of PLEK2 as a therapeutic target.

摘要： The tuft cell-group 2 innate lymphoid cell (ILC2) circuit orchestrates rapid type 2 responses upon detecting microbially derived succinate and luminal helminths. Our findings delineate key mechanistic steps involving IP3R2 engagement and Ca2+ flux, governing interleukin-25 (IL-25) production by tuft cells triggered by succinate detection. While IL-17RB has a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells. Tuft cells exhibit constitutive Il25 expression, placing them in an anticipatory state that facilitates rapid production of IL-25 protein for ILC2 activation. Tuft cell IL-17RB is crucial for restraining IL-25 bioavailability, preventing excessive tonic ILC2 stimulation due to basal Il25 expression. Supraoptimal ILC2 stimulation by IL-25 resulting from tuft cell Il17rb deficiency or prolonged succinate exposure induces a state of hypoproliferation in ILC2s, also observed in chronic helminth infection. Our study offers critical insights into the regulatory dynamics of IL-25 in this circuit, highlighting the delicate tuning required for responses to diverse luminal states.