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Kayo Seo, Soo Ki Kim, Soo Ryang Kim, Aya Ohtani, Mana Kobayashi, Airi Kato, Eri Morimoto, Yuka Saijo, Ke Ih Kim, Susumu Imoto, Chi Wan Kim, Yoshihiko Yano, Masatoshi Kudo, Yoshitake Hayashi
BACKGROUND: Sofosbuvir plus ribavirin (RBV) therapy showed higher sustained virological response at 12 weeks after treatment (SVR12) than pegylated interferon (peg-IFN) plus RBV; however, liver function, fibrosis, and hepatocellular carcinoma markers have not been assessed so far. SUMMARY: Patients (n = 21) receiving Sofosbuvir plus RBV and those (n = 24) receiving peg-IFN plus RBV were enrolled in this study. Changes in alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels, platelet (PLT) counts, FIB-4, and aspartate aminotransferase-to-platelet ratio index (APRI) in both groups were assessed in patients achieving SVR12...
2017: Digestive Diseases
Ágata C Cevey, Gerardo A Mirkin, Martín Donato, María J Rada, Federico N Penas, Ricardo J Gelpi, Nora B Goren
Trypanosoma cruzi induces serious cardiac alterations during the chronic infection. Intense inflammatory response observed from the beginning of infection, is critical for the control of parasite proliferation and evolution of Chagas disease. Peroxisome proliferator-activated receptors (PPAR)-α, are known to modulate inflammation. In this study we investigated whether a PPAR-α agonist, Fenofibrate, improves cardiac function and inflammatory parameters in a murine model of T. cruzi infection. BALB/c mice were sequentially infected with two T...
October 7, 2017: International Journal for Parasitology, Drugs and Drug Resistance
Long Gao, Bo Liu, Wei Mao, Ruifeng Gao, Shuangyi Zhang, Duritahala, Changqi Fu, Yuan Shen, Ying Zhang, Nan Zhang, Jindi Wu, Yang Deng, Xing Wu, Jinshan Cao
The prostaglandin E2 receptor 2 (PTGER2) is present in the endometrium and its gene expression is accompanied with endometrial growth, however, it is unknown whether there is endometrial repair through stimulation of growth factor gene expression that is promoted by PTGER2 activation in cattle. The aim of this study was to investigate whether PTGER2 activation can induce prostaglandin-endoperoxide synthase-2 (PTGS-2) and growth factor gene expression by activating PKA and ERK signaling pathways in endometrial epithelial cells of cattle...
October 10, 2017: Animal Reproduction Science
Dinorath Olvera, Binulal N Sathy, Simon F Carroll, Daniel J Kelly
The ideal tissue engineering (TE) strategy for ligament regeneration should recapitulate the bone - calcified cartilage - fibrocartilage - soft tissue interface. Aligned electrospun-fibers have been shown to guide the deposition of a highly organized extracellular matrix (ECM) necessary for ligament TE. However, recapitulating the different tissues observed in the bone-ligament interface using such constructs remains a challenge. This study aimed to explore how fiber alignment and growth factor stimulation interact to regulate the chondrogenic and ligamentous differentiation of mesenchymal stem cells (MSCs)...
October 7, 2017: Acta Biomaterialia
Cheng-Ning Yang, Min-Fang Wu, Chung-Chih Liu, Wei-Hung Jung, Yu-Chin Chang, Wang-Pao Lee, Young-Ji Shiao, Chia-Lin Wu, Horng-Huei Liou, Sze-Kwan Lin, Chih-Chiang Chan
Impaired clearance of amyloid-β peptide (Aβ) leads to abnormal extracellular accumulation of this neurotoxic protein that drives neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD patients. However, the role of CTGF in AD pathogenesis remains unclear. Here we characterized the neuroprotective activity of CTGF. We found that CTGF facilitated Aβ uptake and subsequent degradation within primary glia and neuroblastoma cells...
October 15, 2017: Human Molecular Genetics
Roger Hullin, Mélanie Métrich, Alexandre Sarre, Denis Basquin, Marc Maillard, Julien Regamey, David Martin
Aims: Clinical studies suggest beneficial effects of renin-angiotensin system blockade for prevention of left ventricular (LV) dysfunction after chemotherapy. However, the efficacy of this strategy as primary prevention has been poorly studied. This study aimed at identifying the pathophysiological mechanisms by which mineralocorticoid receptor antagonism (MRA) or angiotensin converting enzyme inhibition (ACEi) provide protection against doxorubicin-induced cardiotoxicity (DIC) in mouse models of acute and chronic toxicity...
September 7, 2017: Cardiovascular Research
Shan Liu, Bing H Wang, Darren J Kelly, Henry Krum, Andrew R Kompa
To address the pathophysiological mechanisms underlying chronic kidney disease with comorbid cardiac dysfunction, we investigated renal and cardiac, functional and structural damage when myocardial infarction (MI) was applied in the setting of kidney injury (induced by 5/6 nephrectomy-STNx). STNx or Sham surgery was induced in male Sprague-Dawley rats with MI or Sham surgery performed 4 weeks later. Rats were maintained for a further 8 weeks. Rats (n = 36) were randomized into four groups: Sham+Sham, Sham+MI, STNx+Sham and STNx+MI...
October 10, 2017: Journal of Cellular and Molecular Medicine
Jung-Chien Cheng, Hsun-Ming Chang, Peter C K Leung
Appropriate trophoblast invasion into the maternal endometrium is essential for successful human implantation and placentation. Connective tissue growth factor (CTGF), also known as CCN2, is a matricellular protein that is expressed in the placenta. Interestingly, the CTGF expression levels in the placenta and serum from patients with severe preeclampsia or fetal growth restriction are higher than those from healthy controls. However, to date, the role of CTGF in the regulation of trophoblast cell invasion remains unclear...
October 1, 2017: Endocrinology
Yo-Chen Chang, Chia-Wei Lin, Ming-Chu Hsieh, Horng-Jiun Wu, Wen-Sheng Wu, Wen-Chuan Wu, Ying-Hsien Kao
Hypoxia-induced retinal neovascularization plays a central role in the pathogenesis of diabetic retinopathy. This study aimed to investigate whether hypoxia leads to the release of nuclear high mobility group box 1 (HMGB1) peptides from cultured retinal pigment epithelial ARPE-19 cells, to determine the effect of HMGB1 on angiogenic cytokine production and elucidate the involved signaling pathways. A chemical hypoxia mimetic agent, cobalt chloride, induced SIRT1 downregulation, HMGB1 nucleocytoplasmic relocation and extracellular release from ARPE-19 cells, implicating its autocrine function...
September 29, 2017: Cellular Signalling
Bing Wang, Lianghai Li, Ping Jin, Mengqiu Li, Jianguo Li
Cardiac inflammation and cardiac fibrosis are important parts of cardiac remodeling following myocardial infarction (MI), which may be the basic mechanisms of the development of chronic heart failure. The nuclear factor (NF)-κB signaling pathway promotes cardiac inflammation and fibrosis. It has reported that hesperetin inhibits cardiac remodeling induced by pressure overload in mice. However, it has remained elusive whether and how hesperetin has a role in cardiac fibrosis post-MI. Therefore, a mouse model of MI was established by left anterior descending coronary artery ligation...
September 2017: Experimental and Therapeutic Medicine
Daniela Gentile, Pietro E Lazzerini, Alessandra Gamberucci, Mariarita Natale, Enrico Selvi, Francesca Vanni, Alessandra Alì, Paolo Taddeucci, Silvia Del-Ry, Manuela Cabiati, Veronica Della-Latta, David J Abraham, Maria A Morales, Rosella Fulceri, Franco Laghi-Pasini, Pier L Capecchi
Objectives: Systemic sclerosis (SSc) is a connective tissue disorder presenting fibrosis of the skin and internal organs, for which no effective treatments are currently available. Increasing evidence indicates that the P2X7 receptor (P2X7R), a nucleotide-gated ionotropic channel primarily involved in the inflammatory response, may also have a key role in the development of tissue fibrosis in different body districts. This study was aimed at investigating P2X7R expression and function in promoting a fibrogenic phenotype in dermal fibroblasts from SSc patients, also analyzing putative underlying mechanistic pathways...
2017: Frontiers in Pharmacology
Maharshi Bhaswant, Lindsay Brown, Andrew J McAinch, Michael L Mathai
SCOPE: Dietary intake of beetroot by humans reduces blood pressure but whether this is caused by nitrate or betanin is not well-defined; neither are effects on other signs of metabolic syndrome. METHODS AND RESULTS: Rats fed a high-carbohydrate, high-fat diet (H) for 16 weeks developed abdominal obesity, hypertension, altered cardiovascular and liver structure and function, and impaired glucose tolerance compared to rats fed a corn starch diet (C). H rats treated with ∼16 mg/kg/day of nitrate either from beetroot juice (H+B) or sodium nitrate (H+N) for the last 8 weeks reduced systolic blood pressure by ∼25 mmHg, improved cardiac structure and function, plasma lipid profile and plasma markers of liver function, reduced inflammatory cell infiltration in heart and liver and decreased left ventricular fibrosis...
September 27, 2017: Molecular Nutrition & Food Research
Lorna C Gilligan, Habibur P Rahman, Anne-Marie Hewitt, Alice J Sitch, Ali Gondal, Anastasia Arvaniti, Angela E Taylor, Martin L Read, Dion Morton, Paul A Foster
Context: Estrogens impact the incidence and progression of colorectal cancer (CRC) although precise molecular mechanisms remain ill-defined. Objective: Pre-receptor estrogen metabolism through steroid sulphatase (STS) and 17β-hydroxysteroid dehydrogenase activity and subsequent non-genomic estrogen signaling in human CRC tissue, in the TCGA COAD dataset, and in in vitro and in vivo CRC models was investigated. The study aimed to define and therapeutically target pathways through which estrogens alter CRC proliferation and progression...
September 13, 2017: Journal of Clinical Endocrinology and Metabolism
Xuejing Duan, Mei Ji, Fengying Deng, Zhe Sun, Zhiyong Lin
OBJECTIVE: The aim of this study was to evaluate the effects of different concentrations of connective tissue growth factor (CTGF) on human periodontal ligament fibroblasts(HPLFs). DESIGN: HPLFs were cultured and identified. Then, different concentrations of CTGF (1, 5, 10, 50, 100ng/ml) were added to the HPLF culture. Next, CCK-8 assays, alkaline phosphatase (ALP) assays, hydroxyproline determination, alizarin red staining methods, Transwell chambers and real-time PCR methods were applied to observe the effects of CTGF on the proliferation, ALP activity, synthesis of collagen, formation of mineralized nodules and migration...
September 18, 2017: Archives of Oral Biology
Jung Ho Kim, Byung Cheol Shin, Won Sang Park, Jaehwi Lee, Hyo-Jeong Kuh
We investigated the combinatorial effects of pentoxifylline (PTX) on the efficacy of gemcitabine (GEM) in a human pancreatic tumor xenograft model. PTX significantly improved the efficacy of GEM, as shown by a 50% reduction in tumor growth rate at 4 weeks of treatment compared with that in animals given GEM alone. The fluorescent drug doxorubicin (DOX) was used to test whether drug delivery was improved by PTX, contributing to the improved efficacy of GEM. PTX given for 2 weeks prior to DOX administration improved drug distribution by 1...
September 23, 2017: Cancer Science
John R Montford, Seth B Furgeson
Lymphangiogenesis appears to accompany renal fibrosis, but signals that regulate the lymphangiogenic growth factor vascular endothelial growth factor C are not well understood. Kinashi et al. have shown that conditionally deleting connective tissue growth factor reduces renal fibrosis, vascular endothelial growth factor C, and lymphangiogenesis. Connective tissue growth factor has pleiotropic effects in the setting of renal fibrosis; this study adds a potentially new mechanism for the profibrotic effects of connective tissue growth factor...
October 2017: Kidney International
Philipp Kasper, Christina Vohlen, Katharina Dinger, Jasmine Mohr, Eva Hucklenbruch-Rother, Ruth Janoschek, Jessica Köth, Jan Matthes, Sarah Appel, Jörg Dötsch, Miguel A Alejandre Alcazar
Childhood obesity is associated with renal diseases. Maternal obesity is a risk factor linked to increased adipocytokines and metabolic disorders in the offspring. Therefore, we studied the impact of maternal obesity on renal-intrinsic insulin and adipocytokine signaling and on renal function and structure. To induce maternal obesity, female mice were fed a high-fat diet (HFD) or a standard diet (SD; control group) prior to mating, during gestation, and throughout lactation. A third group of dams was fed HFD only during lactation (HFD-Lac)...
October 1, 2017: Endocrinology
Katarzyna Wójcik-Pszczoła, Bogdan Jakieła, Hanna Plutecka, Paulina Koczurkiewicz, Zbigniew Madeja, Marta Michalik, Marek Sanak
Fibroblast to myofibroblast transition (FMT) contributes to bronchial wall remodelling in persistent asthma. Among other numerous factors involved, transforming growth factor type β (TGF-β) plays a pivotal role. Recently it has been demonstrated that connective tissue growth factor (CTGF), a matricellular protein, combines with TGF-β in the pathomechanism of many fibrotic disorders. However, it is not clear whether this interaction takes place in asthma as well. Primary cultures of human bronchial fibroblasts from asthmatic and non-asthmatic subjects were used to investigate the impact of CTGF and TGF-β1 on the fibroblast to myofibroblast transition...
September 15, 2017: Cytokine
Pengfei Liu, Wenhua Jiang, Huilai Zhang
Patients with lymphoma are at high risk of developing venous thromboembolism (VTE). The purpose of the present study was to identify the target gene associated with VTE for patients with lymphoma. Microarray data was downloaded from the gene expression omnibus database (GSE17078), which comprised the control group, 27 normal blood outgrowth endothelial cell (BOEC) samples, and the case group, 3 BOEC samples of venous thrombosis with protein C deficiency. Differentially expressed genes (DEGs) were identified by the Limma package of R...
September 2017: Oncology Letters
T Ando, D Charindra, M Shrestha, H Umehara, I Ogawa, M Miyauchi, T Takata
Tissue inhibitor of metalloproteinase-1 (TIMP-1), a member of the TIMP family (TIMP-1 to 4), is highly expressed in various types of cancer and forms a complex with its receptor CD63 and Integrin β1. However, the precise oncogenic mechanism of TIMP-1 remains unclear. Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) are transcription co-activators enhancing the transcription of specific genes related to cell proliferation. But the mechanism of aberrant YAP/TAZ activation in cancer is not fully understood...
September 18, 2017: Oncogene
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