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https://www.readbyqxmd.com/read/29676832/circulating-mirnas-in-acute-new-onset-atrial-fibrillation-and-their-target-mrna-network
#1
Ananília Medeiros Gomes da Silva, Jéssica Nayara Góes de Araújo, Katiene Macêdo de Oliveira, Ana Eloísa Melo Novaes, Mariana Borges Lopes, Júlio César Vieira de Sousa, Antônio Amorim de Araújo Filho, André Ducati Luchessi, Adriana Augusto de Rezende, Mário Hiroyuki Hirata, Vivian Nogueira Silbiger
BACKGROUND: MicroRNAs (miRNAs) are involved in the pathogenesis of atrial fibrillation (AF), acting on development and progression. Our pilot study investigated the expression of six miRNAs and their miRNA-mRNA interactions in patients with acute new-onset AF, well-controlled AF, and normal sinus rhythm (controls). METHODS AND RESULTS: Plasma of acute new-onset AF patients (n = 5) was collected in the emergency room when patients presented with irregular and fast-atrial fibrillation rhythm...
April 20, 2018: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/29672874/review-article-novel-oral-targeted-therapies-in-inflammatory-bowel-disease
#2
REVIEW
J R White, F Phillips, T Monaghan, W Fateen, S Samuel, S Ghosh, G W Moran
BACKGROUND: There is a great unmet clinical need for efficacious, tolerable, economical and orally administrated drugs for the treatment of inflammatory bowel disease (IBD). New therapeutic avenues have become possible including the development of medications that target specific genetic pathways found to be relevant in other immune mediated diseases. AIMS: To provide an overview of recent clinical trials for new generation oral targeted medications that may have a future role in IBD management...
April 19, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29668937/knockdown-of-smad7-with-a-specific-antisense-oligonucleotide-attenuates-colitis-and-colitis-driven-colonic-fibrosis-in-mice
#3
Roberta Izzo, Gerolamo Bevivino, Veronica De Simone, Silvia Sedda, Ivan Monteleone, Irene Marafini, Martina Di Giovangiulio, Angelamaria Rizzo, Eleonora Franzè, Alfredo Colantoni, Angela Ortenzi, Giovanni Monteleone
Background: In Crohn's disease (CD), the pathogenic immune response is associated with high Smad7, an inhibitor of TGF-β1 signaling. Smad7 knockdown with Mongersen, a specific antisense oligonucleotide-containing compound, restores TGF-β1 activity leading to inhibition of inflammatory signals and associates with clinical benefit in CD patients. As TGF-β1 is pro-fibrogenic, it remains unclear whether Mongersen-induced Smad7 inhibition increases the risk of intestinal fibrosis. We assessed the impact of Smad7 inhibition on the course of colitis-driven intestinal fibrosis in mice...
April 13, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29655688/novel-ras-inhibitor-25-o-methylalisol-f-attenuates-epithelial-to-mesenchymal-transition-and-tubulo-interstitial-fibrosis-by-selectively-inhibiting-tgf-%C3%AE-mediated-smad3-phosphorylation
#4
Hua Chen, Tian Yang, Min-Chang Wang, Dan-Qian Chen, Yang Yang, Ying-Yong Zhao
BACKGROUND: Tubulo-interstitial fibrosis (TIF) is the common pathway in the chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) is a major contributor to the TIF by the increased myofibroblasts. Renin-angiotensin system (RAS) is critical mediator on EMT in progressive CKD. Angiotensin II (ANG) mediates EMT and causes TIF by stimulating transforming growth factor-β1 (TGF-β1). RAS activation could further activate TGF-β1. Inhibition of the RAS is one of the most powerful therapies for progressive CKD...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29652528/erk1-2-dependent-gene-expression-contributing-to-tgf%C3%AE-induced-lens-emt
#5
Magdalena C Wojciechowski, Daisy Y Shu, Frank J Lovicu
PURPOSE: This study aims to highlight some of the genes that are differentially regulated by ERK1/2-signaling in TGFβ-induced EMT in lens, and their potential contribution to this pathological process. MATERIALS AND METHODS: Rat lens epithelial explants were cultured with or without TGFβ over a 3-day-culture period to induce EMT, in the presence or absence of UO126 (ERK1/2-signaling inhibitor), both prior to TGFβ-treatment, or 24 or 48 hours after TGFβ-treatment...
April 13, 2018: Current Eye Research
https://www.readbyqxmd.com/read/29643181/smooth-muscle-cells-differentiated-from-human-mesenchymal-stem-cells-regulated-by-microrna-mir-503-and-mir-222-5p-are-suitable-for-vascular-tissue-engineering
#6
Wenduo Gu, Xuechong Hong, Alexandra Le Bras, Witold N Nowak, Shirin Issa Bhaloo, Jiacheng Deng, Yao Xie, Yanhua Hu, Xiong Z Ruan, Qingbo Xu
Tissue-engineered vascular grafts with long-term patency are greatly needed in the clinical settings, and smooth muscle cells (SMCs) are a critical graft component. Human mesenchymal stem cells (MSCs) are used for generating SMCs and understanding the underlying regulatory mechanisms of the MSC-to-SMC differentiation process could improve SMC generation in the clinic. Here, we found that in response to stimulation of transforming growth factor-β 1 (TGFβ1), human umbilical cord-derived MSCs abundantly express the SMC markers α-smooth muscle actin (αSMA), smooth muscle protein 22 (SM22), calponin and smooth muscle myosin heavy chain (SMMHC) at both gene and protein levels...
April 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29621415/mutual-regulation-between-mir-21-and-the-tgf%C3%AE-smad-signaling-pathway-in-human-bronchial-fibroblasts-promotes-airway-remodeling
#7
Zhi-Wei Yu, Ya-Qin Xu, Xiao-Juan Zhang, Jian-Rong Pan, Hong-Xia Xiang, Xiao-Hong Gu, Shan-Bao Ji, Jun Qian
OBJECTIVE: Airway remodeling is an important pathological feature of asthma. Excessive deposition of extracellular matrix (e.g., collagen) secreted from fibroblasts is a major factor contributing to airway remodeling. Currently, the mechanism by which collagen continues to be oversynthesized in the airway remains unclear. In this study, we investigated the role of the microRNA-21 (miR-21) and TGFβ/Smad signaling pathway in human bronchial fibroblasts (HBFs), and explored the regulatory mechanism of airway remodeling...
April 5, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/29610597/immunohistochemical-expression-of-tgf-%C3%AE-1-smad4-smad7-tgf%C3%AE-rii-and-cd68-positive-tam-densities-in-papillary-thyroid-cancer
#8
Koni Ivanova, Irena Manolova, Maria-Magdalena Ignatova, Maya Gulubova
BACKGROUND: Papillary thyroid carcinoma (PTC) accounts for 80% of the thyroid malignancies that are characterised by slow growth and an excellent prognosis. Over-expression of SMAD4 protein restores TGF-β signalling, determines a strong increase in anti-proliferative effect and reduces invasive potential of tumour cells expressing it. AIM: The study aimed to analyse the immunohistochemical expression of TGF-β1 and its downstream phosphorylated SMAD4, element and of the inhibitory SMAD7 PTC variants and their association with the localisation of TAMs within the tumour microenvironment...
March 15, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29607931/ginsenoside-rg1-protects-against-renal-fibrosis-by-regulating-the-klotho-tgf-%C3%AE-1-smad-signaling-pathway-in-rats-with-obstructive-nephropathy
#9
Sha-Sha Li, Ao-Lin He, Zhi-Yong Deng, Qi-Feng Liu
Ginsenoside-Rg1 (G-Rg1) is an agent isolated from Panax ginseng that exerts anti-fibrotic effects; however, the mechanism is still unclear. Herein, we investigated whether G-Rg1 administration can mitigate or reverse unilateral ureteral obstruction (UUO)-induced renal fibrosis by regulating the Klotho/transforming growth factor (TGF)-β1/Smad signaling pathway in rats. Sprague-Dawley male rats were subjected to UUO, and rats in the treatment group were administered G-Rg1 or G-Rg1 plus Klotho short hairpin RNA interference (shRNA), while rats in the control and model groups were administered vehicle for 14 d...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29575577/smad7-deficiency-decreases-iron-and-haemoglobin-through-hepcidin-up-regulation-by-multilayer-compensatory-mechanisms
#10
Peng An, Hao Wang, Qian Wu, Jiaming Wang, Zhidan Xia, Xuyan He, Xinhui Wang, Yan Chen, Junxia Min, Fudi Wang
To maintain iron homoeostasis, the iron regulatory hormone hepcidin is tightly controlled by BMP-Smad signalling pathway, but the physiological role of Smad7 in hepcidin regulation remains elusive. We generated and characterized hepatocyte-specific Smad7 knockout mice (Smad7Alb/Alb ), which showed decreased serum iron, tissue iron, haemoglobin concentration, up-regulated hepcidin and increased phosphor-Smad1/5/8 levels in both isolated primary hepatocytes and liver tissues. Increased levels of hepcidin lead to reduced expression of intestinal ferroportin and mild iron deficiency anaemia...
March 25, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29568864/protective-effect-of-curcumin-against-ultraviolet-a-irradiation%C3%A2-induced-photoaging-in-human-dermal-fibroblasts
#11
Xiaoming Liu, Ruizhi Zhang, Haixia Shi, Xiaobo Li, Yanhong Li, Ahmad Taha, Chunxing Xu
Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)‑induced photoaging. HDFs were treated with 0‑10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation...
March 20, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29556751/anthocyanins-from-black-soybean-seed-coat-prevent-radiation-induced-skin-fibrosis-by-downregulating-tgf-%C3%AE-and-smad3-expression
#12
Sang Woo Park, Jaehoon Choi, Junhyung Kim, Woohhyeok Jeong, Jun Sik Kim, Bae Kwon Jeong, Sung Chul Shin, Jin Hee Kim
The aim of this study was to evaluate the protective effects of anthocyanins from the black soybean seed coat against radiation injury in dermal fibroblasts and mouse skin. Dermal fibroblasts treated with 50 and 100 µg/mL anthocyanins were irradiated with single doses of 20 Gy. Cell viability, intracellular reactive oxygen species (ROS) production, and mRNA expression were measured. A total of 60 mice were used for an in vivo study. A dose of 100 µg/mL anthocyanins was administered daily for 5 days before or after radiation therapy...
March 19, 2018: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29552196/curcumin-may-serve-an-anticancer-role-in-human-osteosarcoma-cell-line-u-2-os-by-targeting-itpr1
#13
Zhanpeng Luo, Dawei Li, Xiaobo Luo, Litao Li, Suxi Gu, Long Yu, Yuanzheng Ma
The present study aimed to determine the mechanisms of action of curcumin in osteosarcoma. Human osteosarcoma U-2 OS cells was purchased from the Cell Bank of the Chinese Academy of Sciences. RNA sequencing analysis was performed for 2 curcumin-treated samples and 2 control samples using Illumina deep sequencing technology. The differentially expressed genes were identified using Cufflink software. Enrichment and protein-protein interaction network analyses were performed separately using cluster Profiler package and Cytoscape software to identify key genes...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29549584/acetylshikonin-from-zicao-ameliorates-renal-dysfunction-and-fibrosis-in-diabetic-mice-by-inhibiting-tgf-%C3%AE-1-smad-pathway
#14
Zezhao Li, Zhen Hong, Zhiqing Peng, Yongcai Zhao, Rusheng Shao
Diabetic nephropathy (DN) is the major cause of end-stage renal disease in diabetic patients. Zicao, a well-known Chinese traditional medicine, has attracted much attention due to its beneficial effects in various medical fields. In this study, we attempted to investigate the effects and mechanisms of action of acetylshikonin, the main ingredient of Zicao, on renal dysfunction in DN. Our results showed that administration with acetylshikonin not only decreased blood urea nitrogen, urine creatinine and the mean kidney-to-body weight ratio in streptozotocin-induced diabetic mice, but also restored the loss of body weight, whereas the blood glucose was not changed...
March 17, 2018: Human Cell
https://www.readbyqxmd.com/read/29545164/interaction-between-orexin-a-and-bone-morphogenetic-protein-system-on-progesterone-biosynthesis-by-rat-granulosa-cells
#15
Shiho Fujita, Toru Hasegawa, Yuki Nishiyama, Satoshi Fujisawa, Yasuhiro Nakano, Takahiro Nada, Nahoko Iwata, Yasuhiko Kamada, Hisashi Masuyama, Fumio Otsuka
The involvement of orexins in reproductive function has been gradually uncovered. However, the functional role of orexins in ovarian steroidogenesis remains unclear. In the present study, we investigated the effects of orexin A on ovarian steroidogenesis by using rat primary granulosa cells that express both OX1 and OX2 receptors for orexins. Treatment with orexin A enhanced progesterone, but not estradiol, biosynthesis induced by FSH, whereas it did not affect basal levels of progesterone or estradiol. In accordance with the effects on steroidogenesis, orexin A increased the mRNA levels of progesterogenic enzymes, including StAR, P450scc and 3βHSD, but not P450arom, and cellular cAMP synthesis induced by FSH...
March 12, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29545117/microrna-181c-promotes-th17-cell-differentiation-and-mediates-experimental-autoimmune-encephalomyelitis
#16
Zimu Zhang, Zhenyi Xue, Ying Liu, Hongkun Liu, Xiangdong Guo, Yan Li, Hongwei Yang, Lijuan Zhang, Yurong Da, Zhi Yao, Rongxin Zhang
Among T helper (Th) cell subsets differentiated from naive CD4+ T cells, IL-17-producing Th17 cells are closely associated with the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and the MS animal model, experimental autoimmune encephalomyelitis (EAE). The modulation of Th17 differentiation offers a potential avenue for treatment. Although a series of microRNAs (miRNAs) that modulate autoimmune disease development have been reported, further studies on miRNA roles in Th17 differentiation and MS pathogenesis are still warranted...
March 12, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29532228/high-mll2-expression-predicts-poor-prognosis-and-promotes-tumor-progression-by-inducing-emt-in-esophageal-squamous-cell-carcinoma
#17
Abulajiang Abudureheman, Julaiti Ainiwaer, Zhichao Hou, Madiniyat Niyaz, Abdugheni Turghun, Ayshamgul Hasim, Haiping Zhang, Xiaomei Lu, Ilyar Sheyhidin
BACKGROUND: MLL2 has been identified as one of the most frequently mutated genes in a variety of cancers including esophageal squamous cell carcinoma (ESCC). However, its clinical significance and prognostic value in ESCC has not been elucidated. In the present study, we aimed to investigate the expression and role of MLL2 in ESCC. METHODS: Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression profile of MLL2. Kaplan-Meier survival analysis and univariate and multivariate Cox analyses were used to investigate the clinical and prognostic significance of MLL2 expression in Kazakh ESCC patients...
March 12, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29524883/halofuginone-attenuates-intervertebral-discs-degeneration-by-suppressing-collagen-i-production-and-inactivating-tgf%C3%AE-and-nf-%C3%B0%C2%BAb-pathway
#18
Linghui Luo, Yong Gao, Cao Yang, Zengwu Shao, Xinghuo Wu, Shuai Li, Liming Xiong, Chao Chen
Most low back pain is caused by intervertebral discs (IVD) degeneration, a disease that prevalence is increasing with age. Halofuginone, an analog of ferbrifugine isolated from plant Dichroa febrifuga, has drawn much attention in recent years for the wide range of bioactivities in malaria, cancer, fibrotic and autoimmune diseases. In this study, we evaluated the benefit effects of halofuginone in IVD degeneration treatment in a validated rabbit puncture model. Halofuginone treatment could attenuate disc degeneration by suppressing the decrease of discs height and nucleus pulposus signal strength...
March 7, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29522906/daily-therapy-with-a-slow-releasing-h-2-s-donor-gyy4137-enables-early-functional-recovery-and-ameliorates-renal-injury-associated-with-urinary-obstruction
#19
Shouzhe Lin, Dameng Lian, Weihua Liu, Aaron Haig, Ian Lobb, Ahmed Hijazi, Hassan Razvi, Jeremy Burton, Matthew Whiteman, Alp Sener
OBJECTIVES: To assess the effects of slow-releasing H2 S donor GYY4137 on post-obstructive renal function and injury following unilateral ureteral obstruction (UUO) by using the UUO and reimplantation (UUO-R) model in rats and to elucidate potential mechanisms by using an in vitro model of epithelial-mesenchymal transition (EMT). METHODS: Male Lewis rats underwent UUO at the left ureterovesical junction. From post-obstructive day (POD) 1-13, rats received daily intraperitoneal (IP) injection of phosphate buffered saline (PBS, 1 mL) or GYY4137 (200 μmol/kg/day in 1 mL PBS, IP)...
March 6, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29521016/dullard-deficiency-causes-hemorrhage-in-the-adult-ovarian-follicles
#20
Tadayoshi Hayata, Masahiko Chiga, Yoichi Ezura, Makoto Asashima, Hidetaka Katabuchi, Ryuichi Nishinakamura, Masaki Noda
In mammals, the ovarian follicles are regulated at least in part by bone morphogenetic protein (BMP) family members. Dullard (also known as Ctdnep1) gene encodes a phosphatase that suppresses BMP signaling by inactivating or degrading BMP receptors. Here we report that the Col1a1-Cre-induced Dullard mutant mice displayed hemorrhagic ovarian cysts, with red blood cells accumulated in the follicles, resulting in infertility. Cells expressing Cre driven by Col1a1 2.3-kb promoter and their descendants were found in granulosa cells in the ovary and in Sertoli cells in the testis...
March 9, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
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