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Molecular Medicine

Wen-Chih Chiang, Yu-Chin Huang, Ten-I Fu, Ping-Min Chen, Fan-Chi Chang, Chun-Fu Lai, Vin-Cent Wu, Shuei-Liong Lin, Yung-Ming Chen
BACKGROUND: Damage to the endothelium due to ischemia reperfusion injury (IRI) leads to a disruption of the microvasculature, which could be influenced by angiopoietin 1 via its effects on endothelium. We investigated the physiological and therapeutic roles of angiopoietin 1 in renal IRI using angiopoietin 1 knockout and over-expression mice. METHODS: Renal IRI was induced by clamping the right renal artery seven days after left uninephrectomy for 25 min followed by reperfusion...
February 13, 2019: Molecular Medicine
Vassili Tchaikovskii, Robert J Desnick, David F Bishop
BACKGROUND: X-linked protoporphyria (XLP) (MIM 300752) is an erythropoietic porphyria due to gain-of-function mutations in the last exon (Ducamp et al., Hum Mol Genet 22:1280-88, 2013) of the erythroid-specific aminolevulinate synthase gene (ALAS2). Five ALAS2 exon 11 variants identified by the NHBLI Exome sequencing project (p.R559H, p.E565D, p.R572C, p.S573F and p.Y586F) were expressed, purified and characterized in order to assess their possible contribution to XLP. To further characterize the XLP gain-of-function region, five novel ALAS2 truncation mutations (p...
January 24, 2019: Molecular Medicine
Alexander P de Porto, Zhe Liu, Regina de Beer, Sandrine Florquin, Onno J de Boer, Rudi W Hendriks, Tom van der Poll, Alex F de Vos
BACKGROUND: Streptococcus pneumoniae is a major causative agent in community-acquired pneumonia and sepsis. Overwhelming lung inflammation during pneumococcal pneumonia may hamper lung function. Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk), a key signaling protein controlling the activation of various immune cells, including macrophages and neutrophils. The aim of this study was to determine whether ibrutinib treatment ameliorates acute lung inflammation during pneumococcal pneumonia...
January 15, 2019: Molecular Medicine
Rose A Willemze, Olaf Welting, Patricia van Hamersveld, Caroline Verseijden, Laurens E Nijhuis, Francisca W Hilbers, Sybren L Meijer, Balthasar A Heesters, Joost H A Folgering, Harold Darwinkel, Philippe Blancou, Margriet J Vervoordeldonk, Jurgen Seppen, Sigrid E M Heinsbroek, Wouter J de Jonge
BACKGROUND: Both the parasympathetic and sympathetic nervous system exert control over innate immune responses. In inflammatory bowel disease, sympathetic innervation in intestinal mucosa is reduced. Our aim was to investigate the role of sympathetic innervation to the intestine on regulation of the innate immune responses. METHODS: In lipopolysaccharide (LPS)-stimulated macrophages, we evaluated the effect of adrenergic receptor activation on cytokine production and metabolic profile...
January 7, 2019: Molecular Medicine
Xiaojun Zhou, Chunmei Xu, Zhiwei Zou, Xue Shen, Tianyue Xie, Rui Zhang, Lin Liao, Jianjun Dong
BACKGROUND: Sulfonylurea receptor 1 (SUR1) is primarily responsible for glucose regulation in normal conditions. Here, we sought to investigate the glucose metabolism characteristics of SUR1-/- rats. METHODS: The TALEN technique was used to construct a SUR1 gene deficiency rat model. Rats were grouped by SUR1 gene knockout or not and sex difference. Body weight; glucose metabolism indicators, including IPGTT, IPITT, glycogen contents and so on; and other molecule changes were examined...
January 7, 2019: Molecular Medicine
Yiting Tang, Rui Zhang, Qianqian Xue, Ran Meng, Xiangyu Wang, Yanliang Yang, Lingli Xie, Xianzhong Xiao, Timothy R Billiar, Ben Lu
BACKGROUND: Caspase-11, a cytosolic receptor of bacterial endotoxin (lipopolysaccharide: LPS), mediates immune responses and lethality in endotoxemia and experimental sepsis. However, the upstream pathways that regulate caspase-11 activation in endotoxemia and sepsis are not fully understood. The aim of this study is to test whether TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling is critical for caspase-11-dependent immune responses and lethality in endotoxemia. METHODS: Mice of indicated genotypes were subjected to endotoxemia or cecum ligation and puncture (CLP) and monitored daily by signs of a moribund state for lethality...
December 27, 2018: Molecular Medicine
Yiliang Wang, Rongze Wang, Feng Li, Yun Wang, Zhen Zhang, Qiaoli Wang, Zhe Ren, Fujun Jin, Kaio Kitazato, Yifei Wang
BACKGROUND: Numerous host cellular factors are exploited by viruses to facilitate infection. Our previous studies and those of others have shown heat-shock protein 90 (Hsp90), a cellular molecular chaperone, is involved in herpes simplex virus (HSV)-1 infection. However, the function of the dominant Hsp90 isoform and the relationship between Hsp90 and HSV-1 α genes remain unclear. METHODS AND RESULTS: Hsp90α knockdown or inhibition significantly inhibited the promoter activity of HSV-1 α genes and downregulated virion protein 16(VP16) expression from virus and plasmids...
December 22, 2018: Molecular Medicine
Trinidad Guijarro, Esmeralda Magro-Lopez, Joana Manso, Ricardo Garcia-Martinez, Maria Jesus Fernandez-Aceñero, Isabel Liste, Alberto Zambrano
BACKGROUND: The multiple biological effects of vitamin D and its novel activities on inflammation and redox homeostasis have raised high expectations on its use as a therapeutic agent for multiple fibrogenic conditions. We have assessed the therapeutic effects of 1α,25-Dihydroxyvitamin D3 , the biologically active form of vitamin D, in the context of lung fibrosis. METHODS: We have used representative cellular models for alveolar type II cells and human myofibroblasts...
December 19, 2018: Molecular Medicine
Rafael Y Brzezinski, Eyal Fisher, Noa Cohen, Etti Zwang, Gabi Shefer, Naftali Stern, David Zeltser, Itzhak Shapira, Shlomo Berliner, Ori Rogowski, Shani Shenhar-Tsarfaty
BACKGROUND: Imbalanced autonomic nervous system (ANS) activity is associated with poor cardiovascular outcome. However, clinically validated biomarkers to assess parasympathetic function are not yet available. We sought to evaluate parasympathetic dysfunction by measuring serum cholinesterase activity and to determine its relationship to high sensitive cardiac troponin T (hs-cTnT) as well as traditional non-invasive parameters of ANS function during exercise in apparently healthy individuals...
December 18, 2018: Molecular Medicine
Hui Yang, Libo Du, Guangjun Wu, Zhenyu Wu, Jeffrey A Keelan
BACKGROUND: Gold nanoparticles (AuNPs) have been widely studied for biomedical applications, although their safety and potential toxicity in pregnancy remains unknown. The aim of this study is to explore the effect of AuNPs maternal exposure at different gestational ages on fetal survival and development, as well as the potential mechanism of AuNPs affecting embryos and fetuses. METHODS: Thirty nm polyethylene glycol (PEG)-coated AuNPs (A30) were administered to pregnant mice via intravenous injection (5 μg Au/g body weight) over three days at either early or late pregnancy...
December 3, 2018: Molecular Medicine
Yue Dong, Li-Li Han, Zhong-Xin Xu
BACKGROUND: There have been a number of reports implicating the association of microRNAs (miRs) and the MAPK signaling pathway with the dopaminergic neuron, which is involved in the development of Parkinson's disease (PD). The present study was conducted with aims of exploring the role of miR-96 in the activation of iNOS and apoptosis of dopaminergic neuron through the MAPK signaling pathway in mice with PD. METHODS: The miR and the differentially expressed gene in PD were screened out and the relationship between them was verified...
November 28, 2018: Molecular Medicine
Yi-Ling Chen, Yuan-Ping Lin, Cheuk-Kwan Sun, Tien-Hung Huang, Hon-Kan Yip, Yen-Ta Chen
BACKGROUND: We tested the hypothesis that extracorporeal shockwave treatment (ESWT) can abolish inflammation and restore urothelial barrier integrity in acute interstitial cystitis by upregulating the fatty acid receptor GPR120. METHODS: A total of 30 female Sprague-Dawley rats were categorized into five groups: (1) sham-operated rats (SC); (2) rats treated with ESWT (SC + ESWT); (3) rats with bladder irritation using 150 mg/kg cyclophosphamide through intraperitoneal injection; (4) cyclophosphamide rats treated with ESWT (cyclophosphamide+ESWT); (5) cyclophosphamide rats treated with GPR120 agonist (cyclophosphamide+GW9508)...
November 27, 2018: Molecular Medicine
Bei Sun, Hao Ou, Fei Ren, Ye Huan, Tao Zhong, Min Gao, Hongwei Cai
BACKGROUND: The neuroprotective role of propofol (PPF) in cerebral ischemia-reperfusion (I/R) has recently been highlighted. This study aimed to explore whether the neuroprotective mechanisms of PPF were linked to its regulation of Ca2+ /CaMKKβ (calmodulin-dependent protein kinase kinase β)/AMPK (AMP-activated protein kinase)/mTOR (mammalian target of rapamycin)/autophagy pathway. METHODS: Cultured primary rat cerebral cortical neurons were treated with oxygen-glucose deprivation and re-oxygenation (OGD/R) to mimic cerebral I/R injury in vitro...
November 23, 2018: Molecular Medicine
Sarah Louise Fishman, Halis Sonmez, Craig Basman, Varinder Singh, Leonid Poretsky
BACKGROUND: Traditional risk factors are insufficient to explain all cases of coronary artery disease (CAD) in patients with diabetes mellitus (DM). Advanced glycation end-products (AGEs) and their receptors may play important roles in the development and progression of CAD. BODY: Hyperglycemia is the hallmark feature of DM. An increase in the incidence of both micro-and macrovascular complications of diabetes has been observed with increased duration of hyperglycemia. This association persists even after glycemic control has been achieved, suggesting an innate mechanism of "metabolic memory...
November 23, 2018: Molecular Medicine
Inge Søkilde Pedersen, Mads Thomassen, Qihua Tan, Torben Kruse, Ole Thorlacius-Ussing, Jens Peter Garne, Henrik Bygum Krarup
BACKGROUND: Gene expression profiles of normal and tumor tissue reflect both differences in biological processes taking place in vivo and differences in response to stress during surgery and sample handling. The effect of cold (room temperature) ischemia in the time interval between surgical removal of the specimen and freezing is described in a few studies. However, not much is known about the effect of warm (body temperature) ischemia during surgery. METHODS: Three women with primary operable breast cancer underwent in situ biopsies from normal breast and tumor tissue prior to radical mastectomy...
November 16, 2018: 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
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