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排序方式: 共有2945条查询结果,搜索用时 46 毫秒
941.
Congenital anomalies of the kidney and urinary tract (CAKUT) include vesicoureteral reflux (VUR). VUR is a complex, genetically heterogeneous developmental disorder characterized by the retrograde flow of urine from the bladder into the ureter and is associated with reflux nephropathy, the cause of 15% of end-stage renal disease in children and young adults. We investigated a man with a de novo translocation, 46,X,t(Y;3)(p11;p12)dn, who exhibits multiple congenital abnormalities, including severe bilateral VUR with ureterovesical junction defects. This translocation disrupts ROBO2, which encodes a transmembrane receptor for SLIT ligand, and produces dominant-negative ROBO2 proteins that abrogate SLIT-ROBO signaling in vitro. In addition, we identified two novel ROBO2 intracellular missense variants that segregate with CAKUT and VUR in two unrelated families. Adult heterozygous and mosaic mutant mice with reduced Robo2 gene dosage also exhibit striking CAKUT-VUR phenotypes. Collectively, these results implicate the SLIT-ROBO signaling pathway in the pathogenesis of a subset of human VUR.  相似文献   
942.
Craniofacial abnormality is one of the major clinical manifestations of Smith-Magenis syndrome (SMS). Previous analyses in a mixed genetic background of several SMS mouse models--including Df(11)17/+ and Df(11)17-1/+, which have 2-Mb and 590-kb deletions, respectively, and Rai1(-/+)--revealed that the penetrance of the craniofacial phenotype appears to be influenced by deletion size and genetic background. We generated an additional strain with a 1-Mb deletion intermediate in size between the two described above. Remarkably, the penetrance of its craniofacial anomalies in the mixed background was between those of Df(11)17 and Df(11)17-1. We further analyzed the deletion mutations and the Rai1(-/+) allele in a pure C57BL/6 background, to control for nonlinked modifier loci. The penetrance of the craniofacial anomalies was markedly increased for all the strains in comparison with the mixed background. Mice with Df(11)17 and Df(11)17-1 deletions had a similar penetrance, suggesting that penetrance may be less influenced by deletion size, whereas that of Rai1(-/+) mice was significantly lower than that of the deletion strains. We hypothesize that potential trans-regulatory sequence(s) or gene(s) that reside within the 590-kb genomic interval surrounding Rai1 are the major modifying genetic element(s) affecting the craniofacial penetrance. Moreover, we confirmed the influence of genetic background and different deletion sizes on the phenotype. The complicated control of the penetrance for one phenotype in SMS mouse models provides tools to elucidate molecular mechanisms for penetrance and clearly shows that a null allele caused by chromosomal deletion can have different phenotypic consequences than one caused by gene inactivation.  相似文献   
943.
944.
The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan (Bgn) and fibromodulin (Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases.  相似文献   
945.
Bi  Ying  Shang  Menghui  Xu  Xiaoting  Ma  Yining  Zang  Xiaonan 《Journal of applied phycology》2022,34(5):2477-2487
Journal of Applied Phycology - The phycobilisomes attached to the outer side of the thylakoid membrane absorb and transmit light energy in cyanobacteria and red algae. They consist of...  相似文献   
946.

Brain ischemia reperfusion injury (BIRI) is defined as a series of brain injury accompanied by inflammation and oxidative stress. Astrocyte-derived extracellular vesicles (EVs) are importantly participated in BIRI with involvement of microRNAs (miRs). Our study aimed to discuss the functions of miR-29a from astrocyte-derived EVs in BIRI treatment. Thus, astrocyte-derived EVs were extracted. Oxygen and glucose deprivation (OGD) cell models and BIR rat models were established. Then, cell and rat activities and pyroptosis-related protein levels in these two kinds of models were detected. Functional assays were performed to verify inflammation and oxidative stress. miR-29a expression in OGD cells and BIR rats was measured, and target relation between miR-29a and tumor protein 53-induced nuclear protein 1 (TP53INP1) was certified. Rat neural function was tested. Astrocyte-derived EVs improved miR-29a expression in N9 microglia and rat brains. Astrocyte-derived EVs inhibited OGD-induced injury and inflammation in vitro, reduced brain infarction, and improved BIR rat neural functions in vivo. miR-29a in EVs protected OGD-treated cells and targeted TP53INP1, whose overexpression suppressed the protective function of EVs on OGD-treated cells. miR-29a alleviated OGD and BIRI via downregulating TP53INP1 and the NF-κB/NLRP3 pathway. Briefly, our study demonstrated that miR-29a in astrocyte-derived EVs inhibits BIRI by downregulating TP53INP1 and the NF-κB/NLRP3 axis.

  相似文献   
947.
大熊猫是中国特有的珍稀物种,西氏贝蛔虫是危害大熊猫最为严重的一种肠道寄生性线虫。针对目前长期药物驱虫导致的大熊猫西氏贝蛔虫耐药及生态污染问题,苏力菌(Bacillus thuringiensis,Bt)晶体蛋白Cry5B因其特异的线虫杀灭活性,是一种理想的新型抗蛔虫病药物候选。本研究拟通过原核表达方式产生Bt YBT-1518重组Cry5B蛋白,并评价其对大熊猫西氏贝蛔虫的离体杀灭活性。结果表明,Bt YBT-1518 Cry5B由1 246个氨基酸组成,分子量(MW)为139.889 kDa,包含Endotoxin_N、δ-Endotoxin_C、Endotoxin_C、Endotoxin_C2、Cry1Ac_D5结构域,与Bt PS86Q3晶体蛋白关系最近。重组Cry5B蛋白在IPTG浓度为1.4 mmol/L时表达量最大,表达于菌体上清液。离体杀灭活性实验表明,重组Cry5B蛋白的大熊猫西氏贝蛔虫抑杀效果具有显著的剂量依赖性,对肠道L4期幼虫第3天的ED50值为14.5 μg/mL,第7天的ED50值为0.16 μg/mL;但对成虫更敏感,仅作用2 d便可显著下降虫体活性,直至死亡,证实重组Cry5B蛋白对大熊猫蛔虫具有较强的毒杀作用。这些结果为后续论证Bt YBT-1518重组Cry5B蛋白可以作为一种新型、环保的抗大熊猫西氏贝蛔虫病药物提供了数据参考。  相似文献   
948.
949.
Hepatocellular carcinoma (HCC), the third leading cause of cancer-associated mortality worldwide, is a major public health problem. Zinc finger protein A20 (A20), an acute phase response gene, is a potent inhibitor of NF-κB signaling. A20 serves a critical role in liver protection, including limiting inflammation following hepatic injury, stimulating hepatocyte growth, and preventing hepatic ischemia-reperfusion injury. A20 is also involved in different processes, including tumorigenesis, progression, and metastasis through multiple mechanisms. Accumulated studies have reported the clinical implications and biological relevance of A20 in the development and progression of HCC. The underlying mechanisms of A20 in HCC include inhibition of epithelial–mesenchymal transition, protein tyrosine kinase 2 activation and Rac family GTPase 1 activity. Combining liver protection with tumor inhibition is a unique advantage of A20, which has the potential to be a novel treatment for promoting liver regeneration following liver resection in patients with HCC with liver cirrhosis. This review discusses the hepato-protective effect of A20 on hepatocytes and its potential role in cancer development, particularly its suppressor effect on HCC.  相似文献   
950.
Excessive plasma triglyceride (TG) and cholesterol levels promote the progression of several prevalent cardiovascular risk factors, including atherosclerosis, which is a leading death cause. Perilipin 5 (Plin5), an important perilipin protein, is abundant in tissues with very active lipid catabolism and is involved in the regulation of oxidative stress. Although inflammation and oxidative stress play a critical role in atherosclerosis development, the underlying mechanisms are complex and not completely understood. In the present study, we demonstrated the role of Plin5 in high-fat-diet-induced atherosclerosis in apolipoprotein E null (ApoE−/−) mice. Our results suggested that Plin5 expressions increased in the artery tissues of ApoE−/− mice. ApoE/Plin5 double knockout (ApoE−/−Plin5−/−) exacerbated severer atherogenesis, accompanied with significantly disturbed plasma metabolic profiles, such as elevated TG, total cholesterol, and low-density lipoprotein cholesterol levels and reduced high-density lipoprotein cholesterol contents. ApoE−/−Plin5−/− exhibited a higher number of inflammatory monocytes and neutrophils, as well as overexpression of cytokines and chemokines linked with an inflammatory response. Consistently, the IκBα/nuclear factor kappa B pathway was strongly activated in ApoE−/−Plin5−/−. Notably, apoptosis was dramatically induced by ApoE−/−Plin5−/−, as evidenced by increased cleavage of Caspase-3 and Poly (ADP-ribose) polymerase-2. In addition, ApoE−/−Plin5−/− contributed to oxidative stress generation in the aortic tissues, which was linked with the activation of phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinases pathways. In vitro, oxidized low-density lipoprotein (ox-LDL) increased Plin5 expression in RAW264.7 cells. Its knockdown enhanced inflammation, apoptosis, oxidative stress, and lipid accumulation, while promotion of Plin5 markedly reduced all the effects induced by ox-LDL in cells. These studies strongly supported that Plin5 could be a new regulator against atherosclerosis, providing new insights on therapeutic solutions.  相似文献   
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