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Molecular Medicine

Mary K Herrick, Kristin M Favela, Richard B Simerly, Naji N Abumrad, Nathan C Bingham
BACKGROUND: Exposure of rodents to chronic high-fat diet (HFD) results in upregulation of inflammatory markers and proliferation of microglia within the mediobasal hypothalamus. Such hypothalamic inflammation is associated with metabolic dysfunction, central leptin resistance, and maintenance of obesity. Bariatric surgeries result in long-term stable weight loss and improved metabolic function. However, the effects of such surgical procedures on HFD-induced hypothalamic inflammation are unknown...
October 24, 2018: Molecular Medicine
Cheng-Ye Zhan, Di Chen, Jin-Long Luo, Ying-Hua Shi, You-Ping Zhang
BACKGROUND: Intestinal barrier dysfunction is a significant clinical problem, commonly developing in a variety of acute or chronic pathological conditions. Herein, we evaluate the effect of microRNA-31 (miR-31) on intestinal barrier dysfunction through NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis. METHODS: Male Sprague-Dawley rats were collected and divided into the sham group, and the cecum ligation and perforation group which was subdivided after CACO-2 cell transfection of different mimic, inhibitor, or siRNA...
October 19, 2018: Molecular Medicine
P Möhnle, S Hirschberger, L C Hinske, J Briegel, M Hübner, S Weis, G Dimopoulos, M Bauer, E J Giamarellos-Bourboulis, S Kreth
BACKGROUND: Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. METHODS: RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31)...
October 17, 2018: Molecular Medicine
Neta Gotlieb, Irena Tachlytski, Yelena Lapidot, Maya Sultan, Michal Safran, Ziv Ben-Ari
BACKGROUND: Vitamin D is a key immune-modulator that plays a role in the innate and adaptive immune systems. Certain pathogens impair the immune defense by downregulating the vitamin D receptor (VDR) pathway. Low serum levels of vitamin D are associated with increased hepatitis B virus (HBV) replication. Our study aimed to assess the in-vitro relationship between HBV production and Vitamin D signaling pathway and to explore the associated mechanism(s). METHODS: HBV transcription and replication was evaluated by qRT-PCR of the HBV-RNA and covalently closed circular DNA (cccDNA)...
October 16, 2018: Molecular Medicine
Yuanlin Xu, Xihong Zhang, Xiufeng Hu, Wenping Zhou, Peipei Zhang, Jiuyang Zhang, Shujun Yang, Yanyan Liu
BACKGROUND: For the study, we determine the potential biomarkers and uncover the regulatory mechanisms of lncRNA MALAT1 / miR-145 / SOX9 axis on the abilities of cell growth and cell metastasis of colorectal cancer. METHODS: Previously published dataset GSE18105 from GEO database was used for microarray analysis to identify differential-expressed lncRNAs and mRNAs. The miRNA which had targeted relationships with both lncRNA and mRNA was predicted using miRCode and Targetscan...
October 3, 2018: Molecular Medicine
Georgina Gyetvai, Cieron Roe, Lamia Heikal, Pietro Ghezzi, Manuela Mengozzi
BACKGROUND: The pro-myelinating effects of leukemia inhibitory factor (LIF) and other cytokines of the gp130 family, including oncostatin M (OSM) and ciliary neurotrophic factor (CNTF), have long been known, but controversial results have also been reported. We recently overexpressed erythropoietin receptor (EPOR) in rat central glia-4 (CG4) oligodendrocyte progenitor cells (OPCs) to study the mechanisms mediating the pro-myelinating effects of erythropoietin (EPO). In this study, we investigated the effect of co-treatment with EPO and LIF...
September 27, 2018: Molecular Medicine
Karie Runcie, Daniel R Budman, Veena John, Nagashree Seetharamu
Antibody-based therapy has revitalized the world of cancer therapeutics since rituximab was first approved for the treatment of Non-Hodgkin's Lymphoma. Monoclonal antibodies against cancer antigens have been successful strategies for only a handful of cancer types due to many reasons including lack of antibody specificity and complex nature of tumor milieu which interfere with antibody efficacy. Polyspecific antibodies are promising class of anti-cancer agents which can be directed at multiple tumor antigens to eradicate tumor cells more precisely and effectively...
September 24, 2018: Molecular Medicine
Lei Liu, Xin-Lu Pang, Wen-Jun Shang, Hong-Chang Xie, Jun-Xiang Wang, Gui-Wen Feng
BACKGROUND: MicroRNAs (miRNAs) contribute to the progression of chronic kidney disease (CKD) by regulating renal homeostasis. This study explored the effects of miR-181a on CKD through the Toll-like receptor (TLR)/nuclear factor-kappa B (NF-κB) pathway by binding to CRY1. METHODS: Seventy male rats were selected and assigned into specific groups: miR-181a mimic, miR-181a inhibitor, and siRNA against CRY1, with each group undergoing different treatments to investigate many different outcomes...
September 18, 2018: Molecular Medicine
Heng Jiang, Fu Yang, Tao Lin, Wei Shao, Yichen Meng, Jun Ma, Ce Wang, Rui Gao, Xuhui Zhou
BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common paediatric spinal deformity. The etiology and pathology of AIS remain unexplained, and have been reported to involve a combination of genetic and epigenetic factors. Since paravertebral muscle imbalance plays an important role in the onset and progression of scoliosis, we aimed to investigate transcriptomic differences by RNA-seq and identify significantly differentially expressed transcripts in two sides of paravertebral muscle in AIS...
September 18, 2018: Molecular Medicine
Rui Zhang, Xiaojun Zhou, Xue Shen, Tianyue Xie, Chunmei Xu, Zhiwei Zou, Jianjun Dong, Lin Liao
BACKGROUND: Sulfonylureas (SUs) are widely prescribed for the treatment of type 2 diabetes (T2DM). Sulfonylurea receptors (SURs) are their main functional receptors. These receptors are also found in kidney, especially the tubular cells. However, the effects of SUs on renal proximal tubular epithelial cells (PTECs) were unclear. METHODS: Three commonly used SUs were included in this study to investigate if different SUs have different effects on the apoptosis of PTECs...
September 4, 2018: Molecular Medicine
George H Sack
Serum amyloid A (SAA) proteins were isolated and named over 50 years ago. They are small (104 amino acids) and have a striking relationship to the acute phase response with serum levels rising as much as 1000-fold in 24 hours. SAA proteins are encoded in a family of closely-related genes and have been remarkably conserved throughout vertebrate evolution. Amino-terminal fragments of SAA can form highly organized, insoluble fibrils that accumulate in "secondary" amyloid disease. Despite their evolutionary preservation and dynamic synthesis pattern SAA proteins have lacked well-defined physiologic roles...
August 30, 2018: Molecular Medicine
Tom Skaria, Esther Bachli, Gabriele Schoedon
BACKGROUND: Endothelial barrier dysfunction characterized by hyperpermeability of the vascular endothelium is a key factor in the pathogenesis of chronic inflammatory diseases and affects clinical outcomes. In states of chronic inflammation, mediators secreted by activated immune cells or vascular endothelium may affect the barrier function and permeability of the vascular endothelium. The matricellular R-spondin family member RSPO3 is produced by inflammatory-activated human monocytes and vascular endothelial cells, but its effects in the regulation of vascular endothelial barrier function remains elusive...
August 29, 2018: Molecular Medicine
Hong Chen, Wenjun Zhou, Yuting Ruan, Lei Yang, Ningning Xu, Rongping Chen, Rui Yang, Jia Sun, Zhen Zhang
BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by pancreatic β-cell failure, which arises from metabolic stress and results in β cell dedifferentiation, leading to β-cell death. Pathological activation of the renin-angiotensin system (RAS) contributes to increase cell stress, while RAS intervention reduces the onset of T2DM in high-risk populations and promotes insulin secretion in rodents. In this study, we investigated whether and how RAS induces β-cell dedifferentiation and the mechanism underlying this process...
August 14, 2018: Molecular Medicine
Hélène Cabanas, Katsuhiko Muraki, Natalie Eaton, Cassandra Balinas, Donald Staines, Sonya Marshall-Gradisnik
BACKGROUND: Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) is a debilitating disorder that is accompanied by reduced cytotoxic activity in natural killer (NK) cells. NK cells are an essential innate immune cell, responsible for recognising and inducing apoptosis of tumour and virus infected cells. Calcium is an essential component in mediating this cellular function. Transient Receptor Potential Melastatin 3 (TRPM3) cation channels have an important regulatory role in mediating calcium influx to help maintain cellular homeostasis...
August 14, 2018: Molecular Medicine
Giovanna Marchetti, Nicole Ziliotto, Silvia Meneghetti, Marcello Baroni, Barbara Lunghi, Erica Menegatti, Massimo Pedriali, Fabrizio Salvi, Ilaria Bartolomei, Sofia Straudi, Fabio Manfredini, Rebecca Voltan, Nino Basaglia, Francesco Mascoli, Paolo Zamboni, Francesco Bernardi
BACKGROUND: Multiple sclerosis (MS) is an inflammatory, demyelinating and degenerative disorder of the central nervous system (CNS). Several observations support interactions between vascular and neurodegenerative mechanisms in multiple sclerosis (MS). To investigate the contribution of the extracranial venous compartment, we analysed expression profiles of internal jugular vein (IJV), which drains blood from CNS, and related plasma protein levels. METHODS: We studied a group of MS patients (n = 19), screened by echo-color Doppler and magnetic resonance venography, who underwent surgical reconstruction of IJV for chronic cerebrospinal venous insufficiency (CCSVI)...
August 9, 2018: Molecular Medicine
Zhun Wu, Wei Huang, Xuegang Wang, Tao Wang, Yuedong Chen, Bin Chen, Rongfu Liu, Peide Bai, Jinchun Xing
BACKGROUND: This study aimed to investigate the effect of over-expressing circular RNA CEP128 (circCEP128) on cell functions and explore the molecular mechanism of which in bladder carcinoma. METHODS: The differentially expressed circRNAs and mRNAs in bladder carcinoma cells and cells in adjacent tissues were screened out using microarray analysis. Expression levels of circRNAs and mRNAs in tissues and cells were determined by qRT-PCR. Expression of SOX11 was detected by western blot...
July 31, 2018: Molecular Medicine
Rong Zhou, Shuya Zhang, Xuejiao Gu, Yuanyuan Ge, Dingjuan Zhong, Yuling Zhou, Lingyun Tang, Xiao-Ling Liu, Jiang-Fan Chen
BACKGROUND: Retinopathy of prematurity (ROP) remains a major cause of childhood blindness and current laser photocoagulation and anti-VEGF antibody treatments are associated with reduced peripheral vision and possible delayed development of retinal vasculatures and neurons. In this study, we advanced the translational potential of adenosine A2A receptor (A2A R) antagonists as a novel therapeutic strategy for selectively controlling pathological retinal neovascularization in oxygen-induced retinopathy (OIR) model of ROP...
July 31, 2018: Molecular Medicine
Fuhua Wang, Huan Wang, Xuejing Liu, Haiyi Yu, Bo Zuo, Zhu Song, Ning Wang, Wei Huang, Guisong Wang
BACKGROUND: The protective effect of Neuregulin-1 (NRG-1) on heart failure is well established. In this study, we assessed whether NRG-1 could protect the heart by mimicking the cardioprotective effects of ischaemic postconditioning (IP). METHODS: We used a myocardial reperfusion injury rat model in vivo to compare the cardioprotective effects of NRG-1(3 μg/kg, iv. at the onset of reperfusion) and IP. In Langendorff isolated heart perfusion experiments, we used the erythroblastic leukaemia viral oncogene homolog 4 (ErbB4) inhibitor AG1478, a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and a mitogen-activated protein/extracellular signal regulated kinase (MEK) inhibitor PD98059 to clarify whether the protective effects of NRG-1and IP depend on the NRG-1/ErbB4 signals and the reperfusion injury salvage kinase (RISK) pathway...
July 31, 2018: Molecular Medicine
Valentina Maria Sofia, Cecilia Surace, Vito Terlizzi, Letizia Da Sacco, Federico Alghisi, Antonella Angiolillo, Cesare Braggion, Natalia Cirilli, Carla Colombo, Antonella Di Lullo, Rita Padoan, Serena Quattrucci, Valeria Raia, Giuseppe Tuccio, Federica Zarrilli, Anna Cristina Tomaiuolo, Antonio Novelli, Vincenzina Lucidi, Marco Lucarelli, Giuseppe Castaldo, Adriano Angioni
BACKGROUND: Recurrent (RP) and chronic pancreatitis (CP) may complicate Cystic Fibrosis (CF). It is still unknown if mutations in genes involved in the intrapancreatic activation of trypsin (IPAT) or in the pancreatic secretion pathway (PSP) may enhance the risk for RP/CP in patients with CF. METHODS: We enrolled: 48 patients affected by CF complicated by RP/CP and, as controls 35 patients with CF without pancreatitis and 80 unrelated healthy subjects. We tested a panel of 8 genes involved in the IPAT, i...
July 27, 2018: Molecular Medicine
Ling Zhang, Hao Wang, Yu Zhao, Jianguo Wang, Patrycja M Dubielecka, Shougang Zhuang, Gangjian Qin, Y Eugene Chin, Race L Kao, Ting C Zhao
BACKGROUND: Histone deacetylases (HDACs) play a critical role in modulating myocardial protection and cardiomyocyte survivals. However, Specific HDAC isoforms in mediating myocardial ischemia/reperfusion injury remain currently unknown. We used cardiomyocyte-specific overexpression of active HDAC4 to determine the functional role of activated HDAC4 in regulating myocardial ischemia and reperfusion in isovolumetric perfused hearts. METHODS: In this study, we created myocyte-specific active HDAC4 transgenic mice to examine the functional role of active HDAC4 in mediating myocardial I/R injury...
July 17, 2018: Molecular Medicine
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