Molecular and Enzymatic Characterization of 9-Cis-epoxycarotenoid Dioxygenases from Mulberry

The Protein Journal - Abscisic acid (ABA) is involved in many physiological regulatory processes in plants, such as leaf shedding, stomatal closure, inhibition of cell elongation, as well as...     

中国生物多样性在线数据处理平台的构建

高质量的生物多样性数据能够为生物多样性的研究与保护提供数据支撑。目前研究人员开发了大量的生物多样性数据处理软件或工具, 包括工作流系统、R语言包、Python语言包和Excel工具等, 但是使用这些软件或工具需要用户安装相应的软件客户端, 并掌握一定的编程语言、软件开发和复杂的Excel公式等知识和技能。为降低用户的学习成本和使用门槛, 本文采用了Browser/Server模式设计技术、Web技术、可视化技术、响应式开发技术、网络爬虫技术、数据处理技术和Solr智能检索技术等, 针对不同维度的生物多样性数据设计和开发了相应的数据处理模块, 构建了中国生物多样性在线数据处理平台(http://dp.iflora.cn/)。该平台能够有效地帮助科研人员对物种名称、地理位置、时间日期和经纬度等数据进行处理, 并提供数据格式转换、数据质量评测和资源统计分析等辅助功能, 帮助科研人员实现零代码和低门槛地处理生物多样性数据, 提供便捷、高效和简单的数据清洗、校正、转换和整合等数据处理渠道, 为生物多样性研究和保护提供信息化技术支持与服务。     

基于生物信息学分析KCNQ1OT1在胃癌中的作用

长非编码RNA KCNQ1OT1在多种肿瘤中高表达,但是在胃癌中的研究较少并且研究结果不一致,其在胃癌中具体的作用机制也缺乏相关研究。通过癌症基因组图谱(The Cancer Genome Atlas, TCGA)公共数据库分析发现:KCNQ1OT1在胃癌中普遍高表达,且高表达KCNQ1OT1的胃癌病人预后不良,它与胃癌多种临床因素密切相关,尤其是与TP53的突变有明显的相关性,而且其表达与免疫细胞浸润明显相关;KCNQ1OT1在胃癌肿瘤细胞系中普遍高表达,敲低后可抑制胃癌肿瘤细胞的增殖能力,共表达网络分析发现,其表达与肿瘤代谢有密切的相关性;谷氨酰胺酶1(glutaminase 1, GLS1)在胃癌中普遍高表达,与预后不良密切相关,KCNQ1OT1与GLS1的表达具有明显的相关性,敲低KCNQ1OT1的表达可抑制GLS1 mRNA的表达,而过表达GLS1可以部分逆转敲低KCNQ1OT1造成的胃癌细胞增殖能力的下降,因此推测KCNQ1OT1可能通过GLS1调控胃癌肿瘤细胞的生长。本研究通过大数据及实验验证了KCNQ1OT1在胃癌中的表达及功能,提示KCNQ1OT1有可能通过调控谷氨酰胺代谢来促进了胃癌的发生发展,这为分子靶向治疗胃癌的临床研究提供了新的靶点和思路。     

Inhibition of Nrf2 promotes the antitumor effect of Pinelliae rhizome in papillary thyroid cancer

We previously reported that Xiaotan Sanjie (XTSJ) decoction can prevent the progression of gastric cancer in vitro and in vivo. Pinelliae rhizome (PR), one component of XTSJ decoction, has an inhibitory effect on the growth and proliferation of tumor cells. The present study investigated the underlying mechanisms of action of PR. Using the human papillary thyroid cancer cell lines, TPC-1 and BCPAP, we found that XTSJ decoction and PR alone decreased cell viability to a similar extent in both cell lines, whereas treatment with XTJS decoction without PR [PR (−)] had a lesser effect. PR treatment inhibited the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in a dose-dependent manner. To investigate the role of Nrf2 in the PR-mediated effects of XTSJ, knockdown of Nrf2 in the tumor cell lines using Nrf2 siRNA (siNrf2) was performed and transfected cells were treated with PR. Silencing of Nrf2 amplified the effects on autophagy, cell viability, apoptosis, and colony formation. Similar results were obtained following treatment with the autophagy inhibitor 3-methyladenine (3-MA). Furthermore, treatment with PR, siNrf2, and/or 3-MA inhibited the MAPK pathway, and analysis of the MAPK pathway components confirmed the role of this pathway in the PR-mediated cellular effects. In mice implanted with siNrf2-transfected cells, the effects of PR were amplified. Taken together, these findings indicate that PR is critical for the inhibitory effects of XTSJ decoction on tumor cell viability and that downregulation of Nrf2 promotes the antitumor effects of PR on papillary thyroid cancer cells.     

Retracted: Upregulated microRNA-15b alleviates ovarian cancer through inhitbition of the PI3K/Akt pathway by targeting LPAR3

Ovarian cancer characterizes as the fourth leading consequence of death associated with cancer for women. Accumulating evidence underscores the vital roles of microRNAs (miRNAs) in preventing ovarian cancer development. Besides, induction of the phosphatidylinositol-3 kinase/serine/threonine kinase (PI3K/Akt) pathway associated with the ovarian cancer cell migration and invasion. The study aims to examine the effects of miR-15b on the proliferation, apoptosis, and senescence of human ovarian cancer cells by binding to lysophosphatidic acid receptor 3 (LPAR3) with the involvement of the PI3K/Akt pathway. The positive expression of LPAR3 protein was detected by immunohistochemistry. Then the interaction between miR-15b and LPAR3 was examined. The possible role of miR-15b in ovarian cancer was explored using gain- and loss-of-function experiments. Subsequently, the functions of miR-15b on PI3K/Akt pathway, proliferation, migration, invasion, senescence and apoptosis of ovarian cancer cells were assessed. Furthermore, in vivo tumorigenicity assay in nude mice was performed. LPAR3 was overexpressed, whereas miR-15b was poorly expressed in ovarian cancer tissues. LPAR3 is a direct target of miR-15b. Restored miR-15b promoted Bax expression, apoptosis, and senescence, inhibited expression of LPAR3 and Bcl-2, the extent of PI3K and Akt phosphorylation, as well as ovarian cancer cell proliferation, migration, and invasion. Further, tumor growth was observed to be prevented by miR-15b overexpression. Collectively, our study demonstrates that miR-15b represses the proliferation and drives the senescence and apoptosis of ovarian cancer cells through the suppression of LPAR3 and the PI3K/Akt pathway, highlighting an antitumorigenic role of miR-15b.     

Contrasting patterns of genetic structure and phylogeography in the marine agarophytes Gelidiophycus divaricatus and G. freshwateri (Gelidiales,Rhodophyta) from East Asia

The evolutionary and population demographic history of marine red algae in East Asia is poorly understood. Here, we reconstructed the phylogeographies of two upper intertidal species endemic to East Asia, Gelidiophycus divaricatus and G. freshwateri. Phylogenetic and phylogeographic inferences of 393 mitochondrial cox1, 128 plastid rbcL, and 342 nuclear ITS2 sequences were complemented with ecological niche models. Gelidiophycus divaricatus, a southern species adapted to warm water, is characterized by a high genetic diversity and a strong geographical population structure, characteristic of stable population sizes and sudden reduction to recent expansion. In contrast, G. freshwateri, a northern species adapted to cold temperate conditions, is genetically relatively homogeneous with a shallow population structure resulting from steady population growth and recent equilibrium. The overlap zone of the two species roughly matches summer and winter isotherms, indicating that surface seawater temperature is a key feature influencing species range. Unidirectional genetic introgression was detected at two sites on Jeju Island where G. divaricatus was rare while G. freshwateri was common, suggesting the occurrence of asymmetric natural hybrids, a rarely reported event for rhodophytes. Our results illustrate that Quaternary climate oscillations have left strong imprints on the current day genetic structure and highlight the importance of seawater temperature and sea level change in driving speciation in upper intertidal seaweed species.     

Thioredoxin-interacting protein deficiency alleviates phenotypic alterations of podocytes via inhibition of mTOR activation in diabetic nephropathy

Thioredoxin-interacting protein (TXNIP) is induced by high glucose (HG), whereupon it acts to inhibit thioredoxin, thereby promoting oxidative stress. We have found that TXNIP knockdown in human renal tubular cells helped prevent the epithelial-to-mesenchymal transition (EMT). Here, we studied the potential effect of TXNIP on podocyte phenotypic alterations in diabetic nephropathy (DN) in vivo and in vitro. In conditionally immortalized mouse podocytes under HG conditions, knocking down TXNIP disrupted EMT, reactive oxygen species (ROS) production, and mammalian target of rapamycin (mTOR) pathway activation. Further, Raptor short hairpin RNA (shRNA), Rictor shRNA, and mTOR specific inhibitor KU-0063794 were used to assess if the mTOR signal pathway is involved in HG-induced EMT in podocytes. We found that Raptor shRNA, Rictor shRNA, and KU-0063794 could all restrain HG-induced EMT and ROS production in podocytes. In addition, antioxidant Tempol or N-acetylcysteine presented a prohibitive effect on HG-induced EMT in podocytes. Streptozotocin was utilized to render equally diabetic in wild-type (WT) control and TXNIP ^−/− (TKO) mice. Diabetes did not increase levels of 24-hr urinary protein, serum creatinine, blood urea nitrogen, and triglyceride in TXNIP ^−/− mice. Podocyte phenotypic alterations and podocyte loss were detected in WT but not in TKO diabetic mice. Oxidative stress was also suppressed in diabetic TKO mice relative to WT controls. Also, TXNIP deficiency suppresses the activation of mTOR in glomeruli of streptozotocin-induced diabetic mice. Moreover, TXNIP expression, mTOR activation, Nox1, and Nox4 could be detected in renal biopsy tissues of patients with DN. This suggests that decreased TXNIP could ameliorate phenotypic alterations of podocytes via inhibition of mTOR in DN, highlighting TXNIP as a promising therapeutic target.     

Activation of NFKB-JMJD3 signaling promotes bladder fibrosis via boosting bladder smooth muscle cell proliferation and collagen accumulation

Chronic cystitis is characterized by the hyperplasia and fibrosis of the bladder wall as well as attenuated compliance of the bladder. To further unravel its underlying molecular mechanism, the role of NFκB-JMJD3 signaling pathway in cystitis induced bladder fibrosis was investigated. Jmjd3 and Col1/3 expression was detected in a cystitis mouse model that was developed by intraperitoneal injection of cyclophosphamide (CYP). Human bladder smooth muscle cells (hBSMCs) were stimulated in vitro with lipopolysaccharide (LPS), and the cell proliferation and collagen accumulation were detected using EdU, CCK8, flow cytometry, qPCR, western blotting and immunofluorescence assays. Furthermore, the effects of NFκB and JMJD3 on cell proliferation and collagen accumulation were investigated using its selective antagonists, JSH23 and GSK-J4, respectively. CYP induced cystitis significantly increased Jmjd3, Col1 and Col3 expression in the bladder muscle cells. Furthermore, LPS stimulation markedly activated NFκB signaling and elevated JMJD3 expression in hBSMCs, and the activation of NFκB-JMJD3 signaling significantly promoted cell proliferation and collagen accumulation by upregulating CCND1 and COL1/3 expression, respectively. Our study reveals the critical role of NFκB-JMJD3 signaling in cystitis induced bladder reconstruction by regulating hBSMC proliferation and extracellular matrix (ECM) deposition, and these findings provide an avenue for effective treatment of patients with cystitis.