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https://www.readbyqxmd.com/read/29051788/emerging-oral-targeted-therapies-in-inflammatory-bowel-diseases-opportunities-and-challenges
#1
REVIEW
Marcel Vetter, Markus F Neurath
To improve quality of life and prevent long-term risks in patients with inflammatory bowel diseases (IBDs: Crohn's disease, ulcerative colitis), it is essential to suppress inflammatory activity adequately. However, corticosteroids are only suitable for therapy of acute flares and the evidence for positive effects of immunosuppressive substances like azathioprine or 6-mercapropurine is mainly limited to maintenance of remission. In addition, only subgroups of patients benefit from biologicals targeting tumour necrosis factor α or α4β7 integrins...
October 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29048575/microrna-binding-site-polymorphisms-in-genes-involved-in-colorectal-cancer-etiopathogenesis-and-their-impact-on-disease-prognosis
#2
Michaela Schneiderova, Alessio Naccarati, Barbara Pardini, Fabio Rosa, Cornelia Di Gaetano, Katerina Jiraskova, Alena Opattova, Miroslav Levy, Karel Veskrna, Veronika Veskrnova, Tomas Buchler, Stefano Landi, Pavel Vodicka, Veronika Vymetalkova
According to the Vogelstein's model of colorectal carcinogenesis, genetic variations in highly penetrant genes may be involved in the colorectal cancer (CRC) pathogenesis. Similarly, aberrant function and/or altered expression of microRNAs (miRNAs) often occur in CRC. In this context, polymorphisms in miRNA-binding sites (miRSNPs) may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and increased susceptibility to common diseases. To explore this phenomenon, we have mined the 3' untranslated regions (3'UTRs) of genes known to be frequently mutated in CRC to search for miRSNPs and tested their association with CRC risk and clinical outcome...
October 17, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29044425/smad7-regulates-proinflammatory-and-prolabor-mediators-in-amnion-and-myometrium
#3
Ratana Lim, Gillian Barker, Martha Lappas
Preterm birth continues to be a significant public health problem. Infection (bacterial and or viral) and inflammation, by stimulating proinflammatory cytokines, adhesion molecules, and matrix metalloproteinase 9 (MMP9), play a central role in the rupture of membranes and myometrial contractions. SMAD7 has been implicated in regulating the inflammatory response; however, no studies have been performed with regard to human labor. In this study, we determined the effect of spontaneous human labor and prolabor mediators on SMAD7 expression in myometrium and fetal membranes...
August 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29033951/sphingosine-1-phosphate-receptor-5-modulates-early-stage-processes-during-fibrogenesis-in-a-mouse-model-of-systemic-sclerosis-a-pilot-study
#4
Katrin G Schmidt, Martina Herrero San Juan, Sandra Trautmann, Lucija Berninger, Anja Schwiebs, Florian M Ottenlinger, Dominique Thomas, Frank Zaucke, Josef M Pfeilschifter, Heinfried H Radeke
Systemic sclerosis (SSc) is a rare multi-organ autoimmune disease characterized by progressive skin fibrosis. Inflammation, type 2 immunity, and fibrogenic processes are involved in disease development and may be affected by sphingolipids. However, details about early-stage pathophysiological mechanisms and implicated mediators remain elusive. The sphingolipid sphingosine-1-phosphate (S1P) is elevated in the sera of SSc patients, and its receptor S1P5 is expressed in skin tissue. Nevertheless, almost nothing is known about the dermatological contribution of S1P5 to inflammatory and pro-fibrotic processes leading to the pathological changes seen in SSc...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28992682/nanocurcumin-mediated-down-regulation-of-telomerase-via-stimulating-tgf%C3%AE-1-signaling-pathway-in-hepatocellular-carcinoma-cells
#5
Molood Shariati, Samira Hajigholami, Ziba Veisi Malekshahi, Maliheh Entezari, Narges Bodaghabadi, Majid Sadeghizadeh
Background: Curcumin, extracted from turmeric, represents enormous potential to serve as an anticancer agent. Telomerase is viewed as a prominent molecular target of curcumin, and Transforming growth factor-β1 (TGFβ1) has proven to be a major inhibitory signaling pathway for telomerase activity. In the current study, we aimed to explore suppressive effects of nanocurcumin on telomerase expression through TGFβ1 pathway in a hepatocellular carcinoma cell line (Huh7). Methods: MTT assay was used to determine the effect of nonocurcumin on viability of Huh7 cells...
October 10, 2017: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/28992620/potential-ameliorative-effects-of-qing-ye-dan-against-cadmium-induced-prostatic-deficits-via-regulating-nrf-2-ho-1-and-tgf-%C3%AE-1-smad-pathways
#6
Lifen Du, Yongfang Lei, Jinglou Chen, Hongping Song, Xinying Wu
BACKGROUND/AIMS: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. METHOD: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status...
October 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28988741/smad7-alleviates-glomerular-mesangial-cell-proliferation-via-the-ros-nf-%C3%AE%C2%BAb-pathway
#7
Nana Lin, Zequan Ji
OBJECTIVE: The aim of this study was to demonstrate that altered gene expression of Smad7regulated NF-κB expression and ROS production on Ang II (Angiotensin II)-induced rat glomerular mesangial cell (GMC) proliferation. METHODS: pAdTrack-CMV-Smad7 was transduced into rat GMC by adeno-transduction using an ADV (adenovirus)-mediated vector in vivo. Diphenylene iodonium chloride (DPI) pre-treated GMC, and blocked ROS generation as determined by DCFH-DA method. Altered expressions of IκBα and p65 were monitored by Western blot analysis and immunofluorescence...
October 5, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28983617/creb1-and-smad3-mediate-tgf%C3%A2-%C3%AE-3%C3%A2-induced-smad7-expression-in-rat-hepatic-stellate-cells
#8
Liang Deng, Lu Huang, Qiongya Guo, Xiaoyu Shi, Keshu Xu
Transforming growth factor (TGF)‑β3 has previously been reported to antagonize hepatic fibrosis in vivo and in vitro. The present study aimed to investigate the mechanism underlying the involvement of TGF‑β3 in hepatic fibrosis. Short hairpin (sh)RNA‑cAMP-responsive element binding protein (CREB) 1 and small interfering (si)RNA‑Smad3 were utilized to silence the expression of CREB1 and Smad3 in hepatic stellate cells (HSCs), whereas the vector pRSV‑CREB1 was used to induce CREB1 overexpression in HSCs...
September 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28970517/human-in-vitro-model-reveals-the-effects-of-collagen-cross-linking-on-keratoconus-pathogenesis
#9
Rabab Sharif, Jesper Hjortdal, Henrik Sejersen, Garett Frank, Dimitrios Karamichos
Keratoconus (KC) is a corneal thinning disorder that leads to severe vision impairment As opposed to corneal transplantation; corneal collagen crosslinking (CXL) is a relatively non-invasive procedure that leads to an increase in corneal stiffness. In order to evaluate the effect of CXL on human corneal stromal cells in vitro, we developed a 3-D in vitro CXL model, using primary Human corneal fibroblasts (HCFs) from healthy patients and Human Keratoconus fibroblasts (HKCs) from KC patients. Cells were plated on transwell polycarbonate membranes and stimulated by a stable vitamin C...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28967304/systemic-smad7-gene-therapy-increases-striated-muscle-mass-and-enhances-exercise-capacity-in-a-dose-dependent-manner
#10
Joseph Maricelli, Yemeserach Bishaw, Bo Wang, Min Du, Buel Dantese Rodgers
Striated muscle wasting occurs with a variety of disease indications, contributing to mortality and compromising life quality. Recent studies indicate that the recombinant adeno-associated viral (serotype 6) Smad7 gene therapeutic, AVGN7, enhances skeletal and cardiac muscle mass and prevents cancer-induced wasting of both tissues. This is accomplished by attenuating ActRIIb intracellular signaling and as a result, the physiological actions of myostatin and other ActRIIb ligands. AVGN7 also enhances isolated skeletal muscle twitch force, but is unknown to similarly improve systemic muscle function, especially exercise capacity...
October 1, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28962196/smad7-overexpressing-rat-bmscs-inhibit-the-fibrosis-of-hepatic-stellate-cells-by-regulating-the-tgf-%C3%AE-1-smad-signaling-pathway
#11
Shi-Pin Wu, Zhi Yang, Fu-Rong Li, Xiao-Di Liu, Hong-Tao Chen, Dong-Na Su
Mesenchymal stem cells (MSCs) are able to differentiate into hepatocytes, promote the regeneration of hepatic cells and inhibit the progression of hepatic fibrosis. Transforming growth factor (TGF)-β1 is one of the key factors in the development of liver fibrosis, which also promotes extracellular matrix (ECM) formation. Drosophila mothers against decapentaplegic 7 (Smad7) is an essential negative regulator in the TGF-β1/Smad signaling pathway. In the present study, bone mesenchymal stem cells (BMSCs) were isolated from rat bone marrow and transfected with lentiviral vectors carrying the Smad7 gene...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28958208/copper-zinc-loaded-montmorillonite-influences-intestinal-integrity-the-expression-of-genes-associated-with-inflammation-tlr4-myd88-and-tgf-%C3%AE-1-signaling-pathways-in-weaned-pigs-after-lps-challenge
#12
Lefei Jiao, Chun Chun Wang, Huan Wu, Rong Gong, Fang Hui Lin, Jie Feng, Caihong Hu
This study was aimed at investigating whether dietary copper/zinc-loaded montmorillonite (Cu/Zn-Mt) could alleviate Escherichia coli LPS-induced intestinal injury through pro- and anti-inflammatory signaling pathways (TLRs, NLRs and TGF-β1) in weaned piglets. Eighteen 21-d-old pigs were randomly divided into three groups (control, LPS and LPS + Cu/Zn-Mt). After 21 d of feeding, pigs in the LPS group and LPS + Cu/Zn-Mt group received i.p. administration of LPS, whereas pigs in the control group received saline...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/28948853/tgf-%C3%AE-and-il-6-family-signalling-crosstalk-an-integrated-model
#13
Shabnam Khatibi, Jeff Babon, John Wagner, Jonathan H Manton, Chin Wee Tan, Hong-Jian Zhu, Sam Wormald, Antony W Burgess
Mathematical models for TGF-β and IL-6 signalling have been linked, providing a platform for analyzing the crosstalk between the systems. An integrated IL-6:TGF-β model was developed via a reduced set of reaction equations which incorporate both feedback loops and appropriate time-delays for transcription and translation processes. The model simulates stable, robust and realistic responses to both ligands. Pulsatile (multiple pulses) inputs for both TGF-β and IL-6 have been simulated to investigate the effects of each ligand on the sensitivity, equilibrium and dynamic responses of the integrated signalling system...
June 2017: Growth Factors
https://www.readbyqxmd.com/read/28943901/mir-590-promotes-the-proliferation-of-humscs-and-induces-ecm-synthesis-by-targeting-smad7
#14
Tianming Liu, Yinge Wu, Tengyi Huang, Xuexuan Zhang, Yingmu Cai
MicroRNA (miR)-590 has been established to be a promoter of cell proliferation, migration and invasion, and an inhibitor of apoptosis in numerous cancer cell lines. However, its effects on non-cancer cells remain to be elucidated. miR-590 was transfected into human umbilical cord mesenchymal stem cells (HUMSCs), and the cell proliferation rate was determined using a Cell-Light 5-ethynyl-20-deoxyuridine Apollo 567 kit and the presence of extracellular matrix (ECM) proteins were detected using western blot analysis and immunofluorescence microscopy...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28943430/microrna-21-promotes-osteogenesis-of-bone-marrow-mesenchymal-stem-cells-via-the-smad7-smad1-5-8-runx2-pathway
#15
Xiaoyan Li, Lijia Guo, Yitong Liu, Yingying Su, Yongmei Xie, Juan Du, Jian Zhou, Gang Ding, Hao Wang, Yuxing Bai, Yi Liu
Bone marrow mesenchymal stem cells (BMMSCs) are pluripotent stem cells, and the osteogenic differentiation of BMMSCs has been drawing attention for a long time. Bone formation is regulated by numerous molecular and cellular signaling pathways, and the differentiation of BMMSCs is controlled by a well-defined genetic program. In the present study, we isolated BMMSCs from the bone cavities of wild-type (WT) and microRNA-21 knock-out (miR-21-KO) mice and found that miR-21 was significantly upregulated during the osteogenic differentiation of BMMSCs...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28929107/microrna-195-activates-hepatic-stellate-cells-in-vitro-by-targeting-smad7
#16
Li-Ying Song, Yu-Tao Ma, Cui-Fang Wu, Chun-Jiang Wang, Wei-Jin Fang, Shi-Kun Liu
BACKGROUND AND AIM: Aberrant activation of the TGF-β1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs. The aim of this study was to investigate the role of miRNA-195 in HSCs activation. METHODS: A liver fibrotic rat model induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195. The expression levels of miR-195, Smad7, and α-SMA in HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28928094/identification-of-hypoxia-regulated-angiogenic-genes-in-colorectal-cancer
#17
Shaoqi Zong, Wen Li, Hongjia Li, Susu Han, Shanshan Liu, Qi Shi, Fenggang Hou
The tumour hypoxia would trigger the angiogenesis switch for survival, and increase the ability of cancer cells to invade and metastasis. However, hypoxia regulated genes that invovled in angiogenesis in colorectal cancer (CRC) have not been explored in detail. The aim of this study was to explore angiogenic genes under hypoxia condition in CRC. Here, we found that endothelial cells tube formation and cancer cells invasion ability were promoted even under chronic hypoxia condition (72 h) in colon adenocarcinoma HCT-116 cells...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28926478/characterization-of-spontaneous-hydrocephalus-development-in-the-young-atherosclerosis-prone-mice
#18
Chuanguo Liu, Guorong Li, Pingping Wang, Yan Wang, Jie Pan
Little has been reported on whether abnormal lipid metabolism affects hydrocephalus, although congenital malformations and infectious diseases are major causal factors for hydrocephalus development. In a study on the pathogenesis of atherogenesis in mice, we unexpectedly discovered that hydrocephalus occurred in partial apolipoptotein E (apoE) and low-density lipoprotein receptor (LDLR) double-knockout (apoE/LDLR) mice fed either chow or a high-fat and high-cholesterol diet between the ages of 4 and 12 weeks...
November 8, 2017: Neuroreport
https://www.readbyqxmd.com/read/28905939/curcumin-administration-suppresses-collagen-synthesis-in-the-hearts-of-rats-with-experimental-diabetes
#19
Shuang Guo, Xiang-Wen Meng, Xiao-Song Yang, Xiu-Fen Liu, Chang-Han Ou-Yang, Chao Liu
Cardiac fibrosis is considered the initial change of diabetic cardiomyopathy (DCM). We have shown that curcumin alleviates collagen deposition in DCM, but the mechanism remains unknown. In this study we sought to investigate the effects of curcumin on cardiac fibrosis in vivo and in vitro and to elucidate the underlying mechanisms. Experimental diabetes was induced in rats by injection of low-dose streptozotocin (STZ) combined with high energy diet. The rats were orally treated with curcumin (300 mg·kg(-1)·d(-1)) for 16 weeks...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28888052/mir-21-mediated-suppression-of-smad7-induces-tgf%C3%AE-1-and-can-be-inhibited-by-activation-of-nrf2-in-alcohol-treated-lung-fibroblasts
#20
Lucian T Marts, David E Green, Stephen T Mills, Tamara Murphy, Viranuj Sueblinvong
BACKGROUND: We previously demonstrated that chronic alcohol ingestion augments TGFβ1 expression in the lung fibroblast and increases the risk of fibroproliferative disrepair in a mouse model of acute lung injury. The effect of alcohol on TGFβ1 is mitigated by treatment with sulforaphane (SFP), which can activate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, the mechanisms by which alcohol amplifies, or SFP attenuates, TGFβ1 expression in the fibroblast are not known...
September 9, 2017: Alcoholism, Clinical and Experimental Research
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