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Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"

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https://www.readbyqxmd.com/read/30003291/epigenetic-regulation-of-toll-like-receptors-and-its-roles-in-type-1-diabetes
#1
REVIEW
Zhiguo Xie, Gan Huang, Zhen Wang, Shuoming Luo, Peilin Zheng, Zhiguang Zhou
The immune system can be divided into adaptive immunity and innate immunity. Adaptive immunity has been confirmed to be involved in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, the role of innate immunity in T1D has only been studied recently. T1D is caused by selective autoimmune destruction of pancreatic islet β cells. A series of studies have suggested that TLRs play a critical role in the pathogenesis of T1D. Aberrant TLR signaling will change immune homeostasis and result in immunopathological conditions such as endotoxin shock and autoimmune responses...
July 12, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29987405/inflammation-a-highly-conserved-janus-like-phenomenon-a-gastroenterologist-perspective
#2
REVIEW
Davide Giuseppe Ribaldone, Rinaldo Pellicano, Giovanni Clemente Actis
Inflammation is the result of the loss of host's resilience towards the surrounding world. At gross tissue level, inflammation coincides with fluid leakage from vessels, swelling, and blood stasis and extravasation of mononuclear/macrophage cells. Biochemically, these events lead to anoxia and dramatic changes: interruption of the mitochondrial oxidative phosphorylation, influx of the M1 macrophage subset, which live on anaerobic glycolysis. Fall of ATP then leads to energy shortage and debt. In their chronic forms, these phenomena are now known to mark a number of degenerative disorders that have invaded the Western World since the last century: Parkinson's disease, Alzheimer's syndromes, rheumatic diseases, metabolic diseases...
July 9, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29959475/the-multisystemic-functions-of-foxd1-in-development-and-disease
#3
REVIEW
Paula Quintero-Ronderos, Paul Laissue
Transcription factors (TFs) participate in a wide range of cellular processes due to their inherent function as essential regulatory proteins. Their dysfunction has been linked to numerous human diseases. The forkhead box (FOX) family of TFs belongs to the "winged helix" superfamily, consisting of proteins sharing a related winged helix-turn-helix DNA-binding motif. FOX genes have been extensively present during vertebrates and invertebrates' evolution, participating in numerous molecular cascades and biological functions, such as embryonic development and organogenesis, cell cycle regulation, metabolism control, stem cell niche maintenance, signal transduction, and many others...
June 29, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29959474/expression-of-il-17f-is-associated-with-non-pathogenic-th17-cells
#4
Florian Wanke, Yilang Tang, Konrad Gronke, Sabrina Klebow, Sonja Moos, Judith Hauptmann, Arthi Shanmugavadivu, Tommy Regen, Ilgiz A Mufazalov, Lauren A Gabriel, Sonja Reißig, Andreas Diefenbach, Florian C Kurschus, Ari Waisman
IL-17A and IL-17F share the highest sequence homology of the IL-17 family and signal via the same IL-17RA/RC receptor heterodimer. To better explore the expression of these two cytokines, we used a double reporter mouse strain (IL-17DR mice), where IL-17A expressing cells are marked by enhanced green fluorescent protein (eGFP) while red fluorescence protein (RFP) reports the expression of IL-17F. In steady state, we found that Th17 and γδ T cells only expressed IL-17A, while IL-17F expression was restricted to CD8 T cells (Tc17) and innate lymphoid cells (ILC type 3) of the gut...
June 29, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29959473/co-targeting-plk1-and-mtor-induces-synergistic-inhibitory-effects-against-esophageal-squamous-cell-carcinoma
#5
Ting-Ting Liu, Kai-Xia Yang, Jing Yu, Ying-Ya Cao, Jian-Song Ren, Jia-Jie Hao, Bei-Qing Pan, Sai Ma, Li-Yan Yang, Yan Cai, Ming-Rong Wang, Yu Zhang
Both polo-like kinase 1 (PLK1) and mammalian/mechanistic target of rapamycin (mTOR) are attractive therapeutic targets for cancer therapy. However, the efficacy of the combined inhibition of both pathways for treating esophageal squamous cell carcinoma (ESCC), an aggressive malignancy with poor prognosis, remains unknown. In this study, we found that suppression of PLK1 by specific siRNA or inhibitor attenuated mTOR activity in ESCC cells. Phosphorylated S6, a downstream effector of mTOR signaling, was significantly correlated with overexpression of PLK1 in a subset of ESCC...
June 29, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29955901/trimetazidine-protects-against-myocardial-ischemia-reperfusion-injury-by-inhibiting-excessive-autophagy
#6
Shiyong Wu, Guanglei Chang, Lei Gao, Dan Jiang, Liyou Wang, Guoxing Li, Xuexiu Luo, Shu Qin, Xueli Guo, Dongying Zhang
Trimetazidine (TMZ) has been demonstrated to have protective effects against myocardial ischemia/reperfusion (MI/R) injury. In the present study, we investigated the effects and the underlying mechanisms of TMZ on autophagy during MI/R in vivo and in vitro. In the in vivo study, an animal model of MI/R was induced by coronary occlusion. TMZ (20 mg/kg/day) protected the rat hearts from MI/R-induced heart failure by increasing ejection fraction and fractional shortening and decreasing end-systolic volume, end-diastolic volume, left ventricular (LV) internal diameter at systole, and LV internal diameter at diastole; it alleviated myocardial injury and oxidative stress by decreasing LDH, creatine kinase MB isoenzyme, ROS, and MDA levels and increasing SOD and glutathione peroxidase levels in plasma...
June 29, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29942976/targeting-glutaminase-mediated-glutamine-dependence-in-papillary-thyroid-cancer
#7
Yang Yu, Xiaohui Yu, Chenling Fan, Hong Wang, Renee Wang, Chen Feng, Haixia Guan
Papillary thyroid cancer is a prevalent endocrine malignancy. Although alterations in glutamine metabolism have been reported in several types of hematological and solid tumors, little is known about the functions of glutamine and glutaminolysis-associated proteins in papillary thyroid cancer. Here, we demonstrated the glutamine dependence of papillary thyroid cancer cells, and with the use of RT2 -PCR arrays, we screened for the aberrant overexpression of glutaminase in human papillary thyroid cancer tissues and cells...
June 25, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29934777/targeted-resequencing-of-a-locus-for-heparin-induced-thrombocytopenia-on-chromosome-5-identified-in-a-genome-wide-association-study
#8
Anika Witten, Juliane Bolbrinker, Andrei Barysenka, Matthias Huber, Frank Rühle, Ulrike Nowak-Göttl, Edeltraut Garbe, Reinhold Kreutz, Monika Stoll
Immune-mediated heparin-induced thrombocytopenia (HIT) is the clinically most important adverse drug reaction (ADR) in response to heparin therapy characterized by a prothrombotic state despite a decrease in platelet count. We conducted a genome-wide association study in 96 suspected HIT cases and 96 controls to explore the genetic predisposition for HIT within a case-control pharmacovigilance study followed by replication in additional 86 cases and 86 controls from the same study. One single nucleotide polymorphism (SNP, rs1433265, P = 6...
June 22, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29967942/restoration-of-mucosal-integrity-and-epithelial-transport-function-by-concomitant-anti-tnf%C3%AE-treatment-in-chronic-dss-induced-colitis
#9
Henrike Lenzen, Jiajie Qian, Michael P Manns, Ursula Seidler, Anne Jörns
Impaired salt and water absorption is a hallmark of diarrhea in IBD. In the present study, the therapeutic effect of continuous anti-TNFα treatment on the progression of inflammation and colonic transport dysfunction during chronic dextran sulfate sodium (DSS)-induced colitis was investigated. Chronic colitis was induced by three DSS exposure cycles. Mice received TNFα monoclonal antibody treatment twice weekly after the end of the first 5-day DSS drinking period. Mice developed chronic DSS-induced colitis characterized by a typical immune cell infiltration composed of CD3+ T cells and CD68+ macrophages, both expressing high levels of the pro-inflammatory cytokines IL-1β and TNFα, a loss of NHE3 and PDZK1 in the brush border region of the absorptive enterocyte and a decrease of colonic fluid absorption in vivo, measured by colonic single pass perfusion...
June 20, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29909462/inhibition-of-semaphorin-3a-suppresses-lipopolysaccharide-induced-acute-kidney-injury
#10
Xiaofang Tian, Hua Gan, Yizhou Zeng, Hongfei Zhao, Rong Tang, Yunfeng Xia
Semaphorin-3a (Sema3A), a soluble axon guidance cue, appears to play an important role in the development of acute kidney injury (AKI) and has been regarded as an early diagnostic marker to evaluate the progression of AKI. However, the role of Sema3A in sepsis-associated AKI remains unknown. In this study, lipopolysaccharide (LPS) was used to simulate sepsis-associated AKI and the role of Sema3A in LPS-induced AKI was investigated in vivo and in vitro. In our in vivo study, Sema3A was found in tubular epithelial cells (TECs), which presented a higher level after LPS treatment...
June 16, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29876588/the-regulation-of-skeletal-muscle-fiber-type-composition-by-betaine-is-associated-with-nfatc1-myod
#11
Jingjing Du, Linyuan Shen, Peiwen Zhang, Zhendong Tan, Xiao Cheng, Jia Luo, Xue Zhao, Qiong Yang, Hao Gu, An'an Jiang, Jideng Ma, Qianzi Tang, Long Jin, Surong Shuai, Mingzhou Li, Yanzhi Jiang, Guoqing Tang, Lin Bai, Xuewei Li, Jinyong Wang, Shunhua Zhang, Li Zhu
Increasing evidence indicates that muscular dysfunction or alterations in skeletal muscle fiber-type composition not only are involved in muscle metabolism and function but also can limit functional capacity. Therefore, understanding the mechanisms regulating key events during skeletal myogenesis is necessary. Betaine is a naturally occurring component of commonly eaten foods. Here, we showed that 10 mM betaine supplementation in vitro significantly repressed myoblast proliferation and enhanced myoblast differentiation...
June 6, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29872866/the-lncrna-mir4435-2hg-promotes-lung-cancer-progression-by-activating-%C3%AE-catenin-signalling
#12
Haiyun Qian, Li Chen, Jiangping Huang, Xianghui Wang, Shengwei Ma, Fenghe Cui, Liyun Luo, Li Ling, Kai Luo, Guopei Zheng
Recently, emerging evidence has suggested that long noncoding RNAs (lncRNAs) have crucial roles in cancer progression. Here, we demonstrated that the lncRNA MIR4435-2HG was highly expressed in lung cancer tissues and correlated with histological grades and lymph node metastasis. Phenotypic analysis indicated that MIR4435-2HG knockdown inhibited lung cancer cell proliferation and invasion in vitro and in vivo. Notably, MIR4435-2HG knockdown suppressed the EMT (epithelial-mesenchymal transition) process and cancer stem cell traits of lung cancer cells...
June 5, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29761302/cftr-prevents-neuronal-apoptosis-following-cerebral-ischemia-reperfusion-via-regulating-mitochondrial-oxidative-stress
#13
Ya-Ping Zhang, Yong Zhang, Zhi-Bin Xiao, Yan-Bo Zhang, Jing Zhang, Zhi-Qiang Li, Yao-Bin Zhu
The cystic fibrosis transmembrane conductance regulator (CFTR) is linked to cell apoptosis and abundantly expressed in brain tissue. Mitochondrial oxidative stress plays a key role in activating apoptotic pathway following cerebral ischemia reperfusion (IR) injury. Reduced glutathione (GSH) is exclusively synthesized in cytosol but distributed in mitochondria. In the present study, we investigated whether CFTR affected mitochondrial oxidative stress via regulating GSH and thereby protected neurons against apoptosis following cerebral IR...
May 14, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29754254/interplay-between-cardiac-transcription-factors-and-non-coding-rnas-in-predisposing-to-atrial-fibrillation
#14
REVIEW
Alexander T Mikhailov, Mario Torrado
There is growing evidence that putative gene regulatory networks including cardio-enriched transcription factors, such as PITX2, TBX5, ZFHX3, and SHOX2, and their effector/target genes along with downstream non-coding RNAs can play a potentially important role in the process of adaptive and maladaptive atrial rhythm remodeling. In turn, expression of atrial fibrillation-associated transcription factors is under the control of upstream regulatory non-coding RNAs. This review broadly explores gene regulatory mechanisms associated with susceptibility to atrial fibrillation-with key examples from both animal models and patients-within the context of both cardiac transcription factors and non-coding RNAs...
May 12, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29736604/selective-inhibition-of-receptor-activator-of-nf-%C3%AE%C2%BAb-ligand-rankl-in-hematopoietic-cells-improves-outcome-after-experimental-myocardial-infarction
#15
Svetlana Slavic, Olena Andrukhova, Kristopher Ford, Stephan Handschuh, Nejla Latic, Ursula Reichart, Soleman Sasgary, Claudia Bergow, Lorenz C Hofbauer, Paul J Kostenuik, Reinhold G Erben
The RANK (receptor activator of nuclear factor κB)/RANKL (RANK ligand)/OPG (osteoprotegerin) axis is activated after myocardial infarction (MI), but its pathophysiological role is not well understood. Here, we investigated how global and cell compartment-selective inhibition of RANKL affects cardiac function and remodeling after MI in mice. Global RANKL inhibition was achieved by treatment of human RANKL knock-in (huRANKL-KI) mice with the monoclonal antibody AMG161. huRANKL-KI mice express a chimeric RANKL protein wherein part of the RANKL molecule is humanized...
May 8, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29736603/psoriasin-a-novel-anti-candida-albicans-adhesin
#16
Annelie Brauner, Cathrin Alvendal, Milan Chromek, Konrad H Stopsack, Sophia Ehrström, Jens M Schröder, Nina Bohm-Starke
Candida albicans belongs to the normal microbial flora on epithelial surfaces of humans. However, under certain, still not fully understood conditions, it can become pathogenic and cause a spectrum of diseases, from local infections to life-threatening septicemia. We investigated a panel of antimicrobial proteins and peptides (AMPs), potentially involved in mucosal immunity against this pathogen. Out of six studied AMPs, psoriasin was most up-regulated during a mucosal infection, an acute episode of recurrent Candida vulvovaginitis, although candidacidal activity has not been demonstrated...
May 7, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29730698/klotho-preservation-by-rhein-promotes-toll-like-receptor-4-proteolysis-and-attenuates-lipopolysaccharide-induced-acute-kidney-injury
#17
Fangfang Bi, Fang Chen, Yanning Li, Ai Wei, Wangsen Cao
Renal anti-aging protein Klotho exhibits impressive properties of anti-inflammation and renal protection, however is suppressed early after renal injury, making Klotho restoration an attractive strategy of treating renal inflammatory disorders. Here, we reported that Klotho is enriched in macrophages and Klotho preservation by Rhein, an anthraquinone derived from medicinal plant rhubarb, attenuates lipopolysaccharide (LPS)-induced acute inflammation essentially via promoting toll-like receptor 4 (TLR4) degradation...
May 5, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29934652/targeted-next-generation-sequencing-improves-diagnosis-of-hereditary-spastic-paraplegia-in-chinese-patients
#18
Cong Lu, Li-Xi Li, Hai-Lin Dong, Qiao Wei, Zhi-Jun Liu, Wang Ni, Aaron D Gitler, Zhi-Ying Wu
Hereditary spastic paraplegia (HSP) is a heterogeneous group of neurodegenerative diseases characterized by progressive weakness and spasticity of lower limbs. To clarify the genetic spectrum and improve the diagnosis of HSP patients, targeted next-generation sequencing (NGS) was applied to detect the culprit genes in 55 Chinese HSP pedigrees. The classification of novel variants was based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. Patients remaining negative following targeted NGS were further screened for gross deletions/duplications by multiplex ligation-dependent probe amplification (MLPA)...
July 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29808244/impact-of-toll-like-receptor-4-stimulation-on-human-neonatal-neutrophil-spontaneous-migration-transcriptomics-and-cytokine-production
#19
Steven L Raymond, Russell B Hawkins, Tyler J Murphy, Jaimar C Rincon, Julie A Stortz, María Cecilia López, Ricardo Ungaro, Felix Ellett, Henry V Baker, James L Wynn, Lyle L Moldawer, Daniel Irimia, Shawn D Larson
Neonates rely on their innate immune system, and neutrophils in particular, to recognize and combat life-threatening bacterial infections. Pretreatment with lipopolysaccharide (LPS), a toll-like receptor (TLR) 4 agonist, improves survival to polymicrobial sepsis in neonatal mice by enhancing neutrophil recruitment. To understand the response of human neonatal neutrophils to TLR4 stimulation, ex vivo spontaneous neutrophil migration, neutrophil transcriptomics, and cytokine production in the presence and absence of LPS were measured directly from whole blood of adults, term neonates, and preterm neonates...
July 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29806073/taraxasterol-suppresses-the-growth-of-human-liver-cancer-by-upregulating-hint1-expression
#20
Tianhao Bao, Yang Ke, Yifan Wang, Weiwei Wang, Yuehua Li, Yan Wang, Xiang Kui, Qixin Zhou, Han Zhou, Cheng Zhang, Dongming Zhou, Lin Wang, Chunjie Xiao
Taraxasterol has potent anti-inflammatory and anti-tumor activity. However, the effect and potential mechanisms of Taraxasterol on the growth of human liver cancer have not been clarified. Histidine triad nucleotide-binding protein 1 (Hint1) is a tumor suppressor and its downregulated expression is associated with the development of cancer. Here, we report that Taraxasterol treatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancer cells, but not in non-tumor hepatocytes...
July 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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