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ObjectiveTo observe the relationship between the different stages of type 2 diabetes mellitus (T2DM) and the intestinal flora and verify its underlying mechanism.MethodsT2DM rats were generated by high-fat diet (HFD) combined with intraperitoneal streptozotocin (STZ) injection. The rats were divided into four groups: the control group (fed with normal feed for 1 month), the HFD group (fed with HFD for 1 month), the T2DM group (HFD combined with STZ and blood glucose ≥11.1 mM), and the unformed T2DM model (Un-mod) group (HFD combined with STZ and blood glucose <11.1 mM). Feces were collected, and bacterial communities in the fecal samples were analyzed by 16S rRNA gene sequencing. The content of short-chain fatty acids (SCFAs) in feces was measured by gas chromatography. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of G protein-coupled receptor 41 (GPR41) and GPR43.ResultsAt different stages of T2DM, the intestinal flora and SCFAs content of rats were significantly decreased (all P < .05). Our results indicated that g__Prevotella had a significant negative correlation, and g__Ruminococcus_torques_group and g__lachnoclastic had a significant positive correlation with blood glucose. The content of SCFAs, in particular acetate and butyrate, in rat feces of different stages of T2DM were significantly reduced, as well as GPR41 and GPR43 expression. The results in the Un-mod group were similar to the T2DM group, and the expression of GPR41 and GPR43 proteins were significantly higher than those in the T2DM group (both P < .001).ConclusionThe intestinal flora–SCFAs–GPR41/GPR43 network may be important in the development of T2DM. Decreasing blood glucose levels by regulating the intestinal flora may become a new therapeutic strategy for T2DM, which has very important clinical and social values.  相似文献   
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PurposeTo report the 5-year results from the Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula (pAVF) Creation for Hemodialysis Access.Materials and MethodsThe retrospective review of 107 intent-to-treat (ITT) patients from the pivotal trial provided a long-term follow-up population (LTP) of 85 patients with a median follow-up duration of 50 months (range, 12–60 months). Data evaluated in the LTP group were fistula maturation and usage, secondary procedures, and complications. The Kaplan-Meier analysis of primary patency, assisted primary patency, cumulative patency, and functional patency (time from 2-needle cannulation to abandonment) were performed for the ITT population.ResultsIn the LTP, 99% (84 of 85) of fistulae were mature, with 99% (78 of 79) of patients requiring hemodialysis using their pAVF. Sustained fistula use (2-needle cannulation at the prescribed rate, 2 of 3 sessions) was achieved in 92% (78 of 85) of patients, with 7 patients not using their pAVF because they were not on dialysis (n = 4), were on peritoneal dialysis (n = 2), and refused to use fistula (n = 1). Fistula maintenance was required in 31.8% (27 of 85) of patients and included fistula dysfunction (21.2%), thrombosis (5.9%), cannulation injury (12.9%), and arm swelling (4.7%). The number of procedures performed per patient per year to maintain function and patency was 0.32 (91 of 288) for years 2–5. The cumulative patency rates were 89.5%, 88.4%, 88.4%, 85.6%, and 82.0% for years 1, 2, 3, 4, and 5, respectively. The functional patency was 91.8% at the end of the study. There were no major complications related to pAVF during the long-term follow-up.ConclusionsPercutaneous fistulae have provided clinically effective and durable access for hemodialysis with low complications. The continued use and evaluation of pAVF are warranted.  相似文献   
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《Immunobiology》2022,227(6):152298
PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer.  相似文献   
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《Molecular therapy》2022,30(8):2844-2855
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目的 了解长沙地区无偿献血人群隐匿性乙型肝炎病毒感染(occult hepatitis B virus infection,OBI)流行情况,探讨HBV基因型分布特征和S区氨基酸突变的情况。方法 对长沙地区检测结果为HBsAg-/HBV DNA+的无偿献血血液样本进行HBV血清标志物检测,对其中的OBI样本进行HBV病毒载量检测和S区基因扩增,分析血清学标志物抗HBs与病毒载量检出与否的关系,并对扩增产物进行HBV基因分型和突变位点分析。结果 2019年1月—2020年1月长沙地区173 893份无偿献血标本共确认58例OBI样本,OBI流行率为0.033%;共发现7种血清学模式,抗HBc单独阳性最多,占38.98%,所有样本中抗HBc阳性率为89.83%;16例样本能检测出病毒载量,其中14例样本浓度小于100 IU/ml;抗HBs阳性组和阴性组间的病毒载量检出率无统计学差异;75.0%(12/16)样本扩增出S区序列,基因型均为B型,均发生突变,其中11例的HBsAg抗原决定簇及周边主要亲水区域(major hydrophilic region, MHR)发生氨基酸突变。结论 长沙地区无偿献血者中的OBI感染率在全国属于偏低水平;HBV基因型主要是B型,MHR区的氨基酸突变可能是造成OBI的原因,突变有本地特点。  相似文献   
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目的探讨核仁蛋白16(NOP16)在肺腺癌(LUAD)中的表达及其临床意义。 方法收集并比较癌症基因组图谱数据库(TCGA)中445例LUAD和54例正常肺组织样本NOP16 mRNA表达水平的差异,收集、验证并比较基因表达综合数据库(GEO)中226例LUAD和20例正常肺组织样本NOP16 mRNA表达水平的差异;采用Wilcoxon秩和检验和Kruskal-Wallis H检验比较不同临床病理特征的LUAD患者NOP16 mRNA表达水平的差异;通过Kaplan-Meier法评估NOP16在LUAD中的预后价值;采用基因集富集分析(GSEA)探讨NOP16在LUAD中可能参与的生物学通路;通过肿瘤免疫评估资源(TIMER)数据库评估NOP16 mRNA表达水平与肿瘤浸润性免疫细胞(TIICs)的关系。 结果在LUAD中NOP16 mRNA表达水平明显高于正常肺组织(P<0.01),且不同临床分期、T分期、N分期的LUAD患者NOP16 mRNA表达水平均差异有统计学意义(均P<0.05)。Kaplan-Meier生存分析表明NOP16 mRNA的高表达与LUAD患者的不良预后相关(P<0.05)。GSEA显示在NOP16高表达组,核糖体、DNA复制、错配修复、p53信号通路被显著富集(P<0.05,FDR<0.25)。在LUAD中,NOP16 mRNA表达水平与B细胞(r=-0.22)、CD4+ T细胞(r=-0.25)、CD8+ T细胞(r=-0.12)、中性粒细胞(r=-0.18)、巨噬细胞(r=-0.27)和树突状细胞(r=-0.25)的浸润丰度均呈负相关(均P<0.01)。 结论NOP16有望成为LUAD诊断和预后评估的生物标志物以及免疫治疗的新靶点。  相似文献   
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《Clinical breast cancer》2022,22(6):507-514
Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.  相似文献   
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Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.  相似文献   
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