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https://www.readbyqxmd.com/read/29791859/combining-ngn2-programming-with-developmental-patterning-generates-human-excitatory-neurons-with-nmdar-mediated-synaptic-transmission
#1
Ralda Nehme, Emanuela Zuccaro, Sulagna Dia Ghosh, Chenchen Li, John L Sherwood, Olli Pietilainen, Lindy E Barrett, Francesco Limone, Kathleen A Worringer, Sravya Kommineni, Ying Zang, Davide Cacchiarelli, Alex Meissner, Rolf Adolfsson, Stephen Haggarty, Jon Madison, Matthias Muller, Paola Arlotta, Zhanyan Fu, Guoping Feng, Kevin Eggan
Transcription factor programming of pluripotent stem cells (PSCs) has emerged as an approach to generate human neurons for disease modeling. However, programming schemes produce a variety of cell types, and those neurons that are made often retain an immature phenotype, which limits their utility in modeling neuronal processes, including synaptic transmission. We report that combining NGN2 programming with SMAD and WNT inhibition generates human patterned induced neurons (hpiNs). Single-cell analyses showed that hpiN cultures contained cells along a developmental continuum, ranging from poorly differentiated neuronal progenitors to well-differentiated, excitatory glutamatergic neurons...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29789558/celastrol-alleviates-renal-fibrosis-by-upregulating-cannabinoid-receptor-2-expression
#2
Ming Tang, Xu Cao, Kun Zhang, You Li, Quan-You Zheng, Gui-Qing Li, Qian-Hui He, Shu-Jing Li, Gui-Lian Xu, Ke-Qin Zhang
Renal fibrosis is the final manifestation of various chronic kidney diseases, and no effective therapy is available to prevent or reverse it. Celastrol, a triterpene that derived from traditional Chinese medicine, is a known potent anti-fibrotic agent. However, the underlying mechanisms of action of celastrol on renal fibrosis remain unknown. In this study, we found that celastrol treatment remarkably attenuated unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis. This was evidenced by the significant reduction in tubular injury; collagen deposition; accumulation of fibronectin, collagen I, and α-smooth muscle actin; and the expression levels of pro-fibrotic factors Vim, Cola1, and TGF-β1 mRNA, as well as inflammatory responses...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29789443/low-intensity-pulsed-ultrasound-stimulation-facilitates-in-vitro-osteogenic-differentiation-of-human-adipose-derived-stem-cells-via-up-regulation-of-heat-shock-protein-hsp-70-hsp90-and-bone-morphogenetic-protein-bmp-signaling-pathway
#3
Zhonglei Zhang, Yalin Ma, Shaowen Guo, Yi He, Gang Bai, Wenjun Zhang
Low-intensity pulsed ultrasound (LIPUS) has positive effects on osteogenic differentiation. However, the effect of LIPUS on osteogenic differentiation of human adipose-derived stem cells (hASCs) is unclear. In the present study, we investigated whether LIPUS could promote the proliferation and osteogenic differentiation of hASCs. hASCs were isolated and osteogenically induced with LIPUS stimulation at 20 and 30 mW cm-2 for 30 min day-1 Cell proliferation and osteogenic differentiation potential of hASCs were respectively analyzed by cell counting kit-8 assay, Alizarin Red S staining, real-time polymerase chain reaction, and Western blotting...
May 29, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29789425/a-heterodimer-formed-by-bone-morphogenetic-protein-9-bmp9-and-bmp10-provides-most-bmp-biological-activity-in-plasma
#4
Emmanuelle Tillet, Marie Ouarné, Agnès Desroches-Castan, Christine Mallet, Mariela Subileau, Robin Didier, Anna Lioutsko, Guillaume Belthier, Jean-Jacques Feige, Sabine Bailly
Bone morphogenetic protein 9 (BMP9) and BMP10 are the two high-affinity ligands for the endothelial receptor activin receptor-like kinase 1 (ALK1) and are key regulators of vascular remodeling. They are both present in the blood, but their respective biological activities are still a matter of debate. The aim of the present work was to characterize their circulating forms to better understand how their activities are regulated in vivo. First, by cotransfecting BMP9 and BMP10, we found that both can form a disulfide-bonded heterodimer in vitro and that this heterodimer is functional on endothelial cells via ALK1...
May 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29788434/a-novel-mouse-model-of-testicular-granulosa-cell-tumors
#5
Xin Fang, Nan Ni, Yang Gao, David F Vincent, Laurent Bartholin, Qinglei Li
STUDY QUESTION: What is the role of dysregulated transforming growth factor beta (TGFB) signaling in the development of sex cord-stromal tumors in the testis? SUMMARY ANSWER: Overactivation of TGFB signaling results in the development of testicular tumors resembling granulosa cell tumors (GrCTs). WHAT IS KNOWN ALREADY: In an earlier study, we demonstrated that constitutively active TGFB receptor 1 (TGFBR1) in ovarian somatic cells promotes the development of ovarian GrCTs...
May 21, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29786750/microrna%C3%A2-20b%C3%A2-5p-promotes-ventricular-remodeling-by-targeting-the-tgf%C3%A2-%C3%AE-smad-signaling-pathway-in-a-rat-model-of-ischemia%C3%A2-reperfusion-injury
#6
Zhao-Guang Liang, Hong Yao, Rong-Sheng Xie, Chun-Lin Gong, Ye Tian
Myocardial ischemic injury results from severe impairment of the coronary blood supply and may lead to metabolic and ultrastructural changes, thereby causing irreversible damage. MicroRNA (miR)‑20b‑5p has been demonstrated to be involved in malignancies of the breast, colorectum, stomach, blood and oropharynx. The present study aimed to investigate the effects of miR‑20b‑5p on ventricular remodeling following myocardial ischemia‑reperfusion (IR) injury in rats by targeting small mothers against decapentaplegic homolog 7 (Smad7) via the transforming growth factor‑β (TGF‑β)/Smad signaling pathway...
May 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29785090/semen-brassicae-ameliorates-hepatic-fibrosis-by-regulating-transforming-growth-factor-%C3%AE-1-smad-nuclear-factor-%C3%AE%C2%BAb-and-akt-signaling-pathways-in-rats
#7
Si Cao, Baoping Zheng, Tao Chen, Xinfeng Chang, Bao Yin, Zhihua Huang, Ping Shuai, Limin Han
Purpose: There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. Methods: Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL·kg-1 ) at a dose of 200 mg·kg-1 twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29784997/mechanics-guided-embryonic-patterning-of-neuroectoderm-tissue-from-human-pluripotent-stem-cells
#8
Xufeng Xue, Yubing Sun, Agnes M Resto-Irizarry, Ye Yuan, Koh Meng Aw Yong, Yi Zheng, Shinuo Weng, Yue Shao, Yimin Chai, Lorenz Studer, Jianping Fu
Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo...
May 21, 2018: Nature Materials
https://www.readbyqxmd.com/read/29781524/tgf-%C3%AE-signalling-in-renal-fibrosis-from-smads-to-non-coding-rnas
#9
Patrick Ming-Kuen Tang, Ying-Ying Zhang, Thomas Shiu-Kwong Mak, Philip Chiu-Tsun Tang, Xiao-Ru Huang, Hui-Yao Lan
Transforming growth factor-β (TGF-β) is the key player in tissue fibrosis. However, antifibrotic therapy targeting this multifunctional protein may interfere other physiological processes to cause side effects. Thus, precise therapeutic targets are needed to be identified by further understanding the underlying mechanisms of TGF-β1 signalling during fibrogenesis. Equilibrium of Smad signalling is crucial for TGF-β-mediated renal fibrosis, where Smad3 is pathogenic but Smad2 and Smad7 are protective. The activation of TGF-β1/Smad signalling triggers extracellular matrix deposition, and local myofibroblast generation and activation...
May 21, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29780169/mediator-kinase-cdk8-cdk19-drives-yap1-dependent-bmp4-induced-emt-in-cancer
#10
Anne Serrao, Laura M Jenkins, Alexander A Chumanevich, Ben Horst, Jiaxin Liang, Michael L Gatza, Nam Y Lee, Igor B Roninson, Eugenia V Broude, Karthikeyan Mythreye
CDK8 is a transcription-regulating kinase that controls TGF-β/BMP-responsive SMAD transcriptional activation and turnover through YAP1 recruitment. However, how the CDK8/YAP1 pathway influences SMAD1 response in cancer remains unclear. Here we report that SMAD1-driven epithelial-to-mesenchymal transition (EMT) is critically dependent on matrix rigidity and YAP1 in a wide spectrum of cancer models. We find that both genetic and pharmacological inhibition of CDK8 and its homologous twin kinase CDK19 leads to abrogation of BMP-induced EMT...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29779217/ginsenoside-c-mx-isolated-from-notoginseng-stem-leaf-ginsenosides-attenuates-ultraviolet-b-mediated-photoaging-in-human-dermal-fibroblasts
#11
Xiao-Yi Liu, Eunson Hwang, Bom Park, Hien T T Ngo, Yong-Kun Xiao, Tae-Hoo Yi
Notoginseng is a traditional herbal medicine widely used for medicinal therapy in Asia, as it contains numerous ginsenosides with pharmacological effects. In this study, we submitted Notoginseng stem-leaf (NGL) ginsenosides to an enzyme to create reaction the monomer products of ginsenoside C-Mx and then investigated the ability of ginsenoside C-Mx to protect the skin against ultraviolet B-induced injury in normal human dermal fibroblasts (NHDFs). Ginsenoside C-Mx alleviated UVB-induced intracellular reactive oxygen species (ROS), MMP-1, and IL-6 expression while accelerating TGF-β and procollagen type I secretion...
May 20, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29767852/membrane-tethered-syntaxin-4-locally-abrogates-e-cadherin-function-and-activates-smad-signals-contributing-to-asymmetric-mammary-epithelial-morphogenesis
#12
Yuina Hirose, Kota Shirai, Yohei Hirai
Spatial and temporal epithelial-mesenchymal transition (EMT) is a critical event for the generation of asymmetric epithelial architectures. We found that only restricted cell populations in the morphogenic mammary epithelia extrude syntaxin-4, a plasmalemmal t-SNARE protein, and that epithelial cell clusters with artificial heterogenic presentation of extracellular syntaxin-4 undergo asymmetric morphogenesis. A previous study revealed that inducible expression of cell surface syntaxin-4 causes EMT-like cell behaviors in the clonal mammary epithelial cells, where laminin-mediated signals were abolished so that cells readily succumb to initiate EMT...
May 16, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29767241/transcriptome-sequencing-analysis-reveals-the-effect-of-combinative-treatment-with-low%C3%A2-intensity-pulsed-ultrasound-and-magnesium-ions-on-hfob1-19-human-osteoblast-cells
#13
Haiyue Zu, Xueting Yi, Dewei Zhao
Biodegradable magnesium (Mg) materials are considered ideal as osteosynthesis implants. However, clinical application has proven complex. This is primarily associated with the issue of reducing the extent of implant degradation to a range acceptable for the human body, while simultaneously enhancing osteogenesis or osteoinduction. In the present study, a combination of Mg ions and low‑intensity pulsed ultrasound (LIPUS) treatment was applied in hFOB 1.19 human osteoblast cells as a potential strategy to resolve this issue...
May 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29764993/-smad3-gene-rs12901499-polymorphism-increased-the-risk-of-osteoarthritis
#14
Hao-Yu Yang, Wen-Hao Hu, Tao Jiang, Hui Zhao
A growing body of evidence suggested that smad family member 3 gene rs12901499 polymorphism was associated with the risk of osteoarthritis. However, the results of previous studies were conflicting. In the present study, we assessed whether smad family member 3 gene rs12901499 polymorphism was associated with the risk of osteoarthritis by the meta-analysis. We searched in the databases of PubMed, Embase, and CNKI. Pooled odds ratios and 95% confidence intervals were calculated. Seven papers involving 11 studies (5344 cases and 9080 controls) analyzed the association between smad family member 3 gene rs12901499 polymorphism and osteoarthritis risk...
May 15, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29764006/tectorigenin-promotes-osteoblast-differentiation-and-in-vivo-bone-healing-but-suppresses-osteoclast-differentiation-and-in-vivo-bone-resorption
#15
So-Youn Lee, Gyu-Tae Kim, Hyung-Mun Yun, Youn-Chul Kim, Il-Keun Kwon, Eun-Cheol Kim
Although Tectorigenin (TG), a major compound in the rhizome of Belamcanda chinensis, is conventionally used for the treatment of inflammatory diseases, its effects on osteogenesis and osteoclastogenesis have not been reported. The objective of this study was to investigate the effects and possible underlying mechanism of TG on in vitro osteoblastic differentiation and in vivo bone formation, as well as in vitro osteoclast differentiation and in vivo bone resorption. TG promoted the osteogenic differentiation of primary osteoblasts and periodontal ligament cells...
May 15, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29761840/ginsenoside-rg1-ameliorates-liver-fibrosis-via-suppressing-epithelial-to-mesenchymal-transition-and-reactive-oxygen-species-production-in-vitro-and-in-vivo
#16
Xiaoyu Wei, Yatang Chen, Wenxiang Huang
Liver fibrosis remains a major cause of morbidity and mortality with a complicated etiology and notorious complications, but there is a lack of efficacious therapeutics. Epithelial to mesenchymal transition (EMT) has a central role in the course of liver fibrosis, and thus, prevention of the development of EMT may control and even reverse liver fibrosis. This study aimed to examine the beneficial effect of ginsenoside Rg1, a phrenological active component isolated from Ginseng, and interrogate the mechanism in vitro and in vivo, with a focus on transforming growth factor-β (TGF-β)/Smad and Nrf2-mediated signaling pathways...
May 15, 2018: BioFactors
https://www.readbyqxmd.com/read/29761481/lncrna-nkila-suppresses-tgf-%C3%AE-induced-epithelial-mesenchymal-transition-by-blocking-nf-%C3%AE%C2%BAb-signaling-in-breast-cancer
#17
Wei Wu, Fei Chen, Xiuying Cui, Limei Yang, Jianing Chen, Jinghua Zhao, Di Huang, Jiang Liu, Linbin Yang, Jiayi Zeng, Zhiqing Zeng, Yunbao Pan, Fengxi Su, Junchao Cai, Zhongfu Ying, Qiyi Zhao, Erwei Song, Shicheng Su
TGF-β plays a central role in mediating epithelial-mesenchymal transition (EMT) by activating the Smad pathway. In addition, accumulating evidence suggests that TGF-β-induced EMT is NF-κB-dependent in various cancer types. However, it is largely unclear if NF-κB mediates TGF-β-induced EMT in breast cancer, and if this mediation occurs, the regulatory mechanisms are unknown. In this study, we found that TGF-β activates the NF-κB pathway. Inhibition of NF-κB signaling markedly abrogates TGF-β-induced EMT...
May 15, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29760746/microrna-495-inhibits-the-high-glucose-induced-inflammation-differentiation-and-extracellular-matrix-accumulation-of-cardiac-fibroblasts-through-downregulation-of-nod1
#18
Xiaowei Wang, Haiying Jin, Shifeng Jiang, Yanlan Xu
Background: MicroRNAs (miRNAs) have physiological and pathophysiological functions that are involved in the regulation of cardiac fibrosis. This study aimed to investigate the effects of miR-495 on high glucose-induced cardiac fibrosis in human cardiac fibroblasts (CFs) and to establish the mechanism underlying these effects. Methods: Human CFs were transfected with an miR-495 inhibitor or mimic and incubated with high glucose. The levels of NOD1 and miR-495 were then determined via quantitative RT-PCR...
2018: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/29753111/irak2-counterbalances-oncogenic-smurf1-in-colon-cancer-cells-by-dictating-er-stress
#19
Jingwen Liu, Yuhan Chen, Qingyang Huang, Wen Liu, Xiqing Ji, Fan Hu, Ying Zhu, Lingqiang Zhang, Guanglong Dong
The endoplasmic reticulum (ER) is a cellular organelle with central roles in maintaining proteostasis. The accumulation of misfolded proteins in the ER lumen causes ER stress. Cells evoke an evolutionarily conserved adaptive signaling network "unfolded protein response" to restore ER homeostasis, however, how the signaling network is delicately orchestrated remains largely unrevealed. Meanwhile, the HECT type E3 ligase Smad ubiquitylation regulatory factor 1 (Smurf1) has been reported to play critical roles in several important biological pathways by targeting distinct substrates for ubiquitylation, including WFS1, a critical mediator of ER stress, whereas the regulation of Smurf1 activity and abundance upon ER stress are poorly understood...
May 9, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29752408/interleukin-6-mediated-trans-signaling-inhibits-transforming-growth-factor-%C3%AE-signaling-in-trabecular-meshwork-cells
#20
Miyuki Inoue-Mochita, Toshihiro Inoue, Sachi Kojima, Akiko Futakuchi, Tomokazu Fujimoto, Saori Sato-Ohira, Utako Tsutsumi, Hidenobu Tanihara
Glaucoma is one of the major causes of blindness, and TGF-β2 has been found to be elevated in the aqueous humor of eyes with primary open-angle glaucoma (POAG). TGF-β2 in aqueous humor causes the glaucoma-related fibrosis of human trabecular meshwork (HTM), suggesting an important role of TGF-β in POAG pathogenesis. Here, we sought to elucidate the effects of IL-6 trans-signaling on TGF-β signaling in HTM cells. Using a multiplex immunoassay, POAG patients decreased IL-6 levels and increased soluble IL-6 receptor (sIL-6R) levels compared with the controls...
May 11, 2018: Journal of Biological Chemistry
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