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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
Weihua Yu, Kongxi Zhu, Yulong Wang, Hualong Yu, Jianqiang Guo
BACKGROUND: This study aims to investigate the effect of miR-21-5p on process of colon adenocarcinoma (COAD) cells and its connection with neural cell adhesion molecule L1 (CHL1). METHODS: Different expressions of mRNAs and miRNAs were calculated with microarray analysis. QRT-PCR and western blot were performed to quantify miR-21-5p and CHL1 expression. Flow Cytometry, MTT assay, colony formation assay, transwell assay and ELISA were performed to evaluate propagation and invasiveness of COAD cells...
July 16, 2018: Molecular Medicine
Jiaqin Yan, Junhui Zhang, Xudong Zhang, Xin Li, Ling Li, Zhaoming Li, Renyin Chen, Lei Zhang, Jingjing Wu, Xinhua Wang, Zhenchang Sun, Xiaorui Fu, Yu Chang, Feifei Nan, Hui Yu, Xiaolong Wu, Xiaoyan Feng, Wencai Li, Mingzhi Zhang
BACKGROUND: This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia induced-chemoresistance in T-cell non-Hodgkin's lymphoma (T-NHL), as well as the underlying molecular mechanisms. METHODS: Expression of AEG-1, LC3-II, and Beclin-1 were initially examined in human T-NHL tissues (n = 30) and normal lymph node tissues (n = 16) using western blot, real-time PCR and immunohistochemistry. Western blot was also performed to analyze the expression of AEG-1, LC3-II, and Beclin-1 in T-NHL cells (Hut-78 and Jurkat cells) under normoxia and hypoxia...
July 9, 2018: Molecular Medicine
Anna Mandel, Per Larsson, Martuza Sarwar, Julius Semenas, Azharuddin Sajid Syed Khaja, Jenny L Persson
BACKGROUND: Metastatic Prostate cancer (PCa) cells have gained survival and invasive advantages. Epidermal growth factor (EGF) receptor is a receptor tyrosine kinase, which may mediate signalling to promote progression and invasion of various cancers. In this study, we uncovered the molecular mechanisms underlying the interconnection among the androgen receptor (AR), matrix metalloproteinase-9 (MMP9) and EGFR in promoting PCa progression. METHODS: Immunohistochemical analysis of the tissue microarrays consisting of primary and metastatic PCa tissues was performed...
June 27, 2018: Molecular Medicine
Ben Ke, Yanxia Chen, Wei Tu, Ting Ye, Xiangdong Fang, Liping Yang
Histone deacetylase 6 (HDAC6), a cytoplasmic enzyme that plays important roles in many biological processes, is one isoform of a family of HDAC enzymes that catalyse the removal of functional acetyl groups from proteins. HDAC6 stands out from the other members of this family because it almost exclusively deacetylates cytoplasmic proteins and exerts deacetylation-independent effects, which has led to the successful development of relatively isoform-specific inhibitors of its enzymatic action. Numerous studies have recently demonstrated that HDAC6 expression and activity are increased in kidney disease, such as autosomal dominant polycystic kidney disease (ADPKD), renal fibrosis, and acute kidney injury (AKI), among others...
June 26, 2018: Molecular Medicine
Sean F Monaghan, Debasree Banerjee, Chun-Shiang Chung, Joanne Lomas-Neira, Kamil J Cygan, Christy L Rhine, William G Fairbrother, Daithi S Heffernan, Mitchell M Levy, William G Cioffi, Alfred Ayala
BACKGROUND: Critically ill patients with sepsis and acute respiratory distress syndrome have severely altered physiology and immune system modifications. RNA splicing is a basic molecular mechanism influenced by physiologic alterations. Immune checkpoint inhibitors, such as B and T Lymphocyte Attenuator (BTLA) have previously been shown to influence outcomes in critical illness. We hypothesize altered physiology in critical illness results in alternative RNA splicing of the immune checkpoint protein, BTLA, resulting in a soluble form with biologic and clinical significance...
June 18, 2018: Molecular Medicine
Mingzhu He, Marco E Bianchi, Tom R Coleman, Kevin J Tracey, Yousef Al-Abed
After publication of this article (He et al., 2018), the corresponding authors recognised an error in Scheme 1, in particular to section "A. HMGB1/TLR4/MD-2 complex formation". Above "Step 2: B box binding to MD-2", the text incorrectly read: "Low affinity / extremely slow off". In addition, some text was omitted below "TLR4/MD-2". The correct version of Scheme 1 is included in this Correction article. The original article (He et al., 2018) has been corrected.
June 13, 2018: Molecular Medicine
Subhayan Chattopadhyay, Hauke Thomsen, Miguel Inacio da Silva Filho, Niels Weinhold, Per Hoffmann, Markus M Nöthen, Arendt Marina, Karl-Heinz Jöckel, Börge Schmidt, Sonali Pechlivanis, Christian Langer, Hartmut Goldschmidt, Kari Hemminki, Asta Försti
BACKGROUND: Recent identification of 10 germline variants predisposing to monoclonal gammopathy of undetermined significance (MGUS) explicates genetic dependency of this asymptomatic precursor condition with multiple myeloma (MM). Yet much of genetic burden as well as functional links remain unexplained. We propose a workflow to expand the search for susceptibility loci with genome-wide interaction and for subsequent identification of genetic clusters and pathways. METHODS: Polygenic interaction analysis on 243 cases/1285 controls identified 14 paired risk loci belonging to unique chromosomal bands which were then replicated in two independent sets (case only study, 82 individuals; case/control study 236 cases/ 2484 controls)...
June 11, 2018: Molecular Medicine
Dimiter Avtanski, Leonid Poretsky
Breast cancer is the most common cancer among women as metastasis is currently the main cause of mortality. Breast cancer cells undergoing metastasis acquire resistance to death signals and increase of cellular motility and invasiveness.Plants are rich in polyphenolic compounds, many of them with known medicinal effects. Various phyto-polyphenols have also been demonstrated to suppress cancer growth. Their mechanism of action is usually pleiotropic as they target multiple signaling pathways regulating key cellular processes such as proliferation, apoptosis and differentiation...
June 5, 2018: Molecular Medicine
Xiao-Yan Luo, Qun Liu, Huan Yang, Qi Tan, Li-Qiang Gan, Fa-Liang Ren, Hua Wang
BACKGROUND: Chronic autoimmune urticaria (CAU) is a common skin disease and remains unclear understanding of pathogenesis in the vast majority of cases. In order to explore a new therapy for CAU, the current study was performed to investigate the possible functioning of the Oncostatin M receptor (OSMR) gene in the autoimmunity of CAU via regulation of the JAK/STAT3 signaling pathway. METHODS: CAU skin tissues from 24 CAU patients and normal skin tissues from normal subjects were collected...
June 5, 2018: Molecular Medicine
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