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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/30178194/high-fat-diet-consumption-reduces-hepatic-folate-transporter-expression-via-nuclear-respiratory-factor-1
#1
Victoria Sid, Yaw L Siow, Yue Shang, Connie W Woo, Karmin O
Folate is an essential micronutrient for biological function. The liver, a primary organ for folate metabolism and storage, plays an important role in folate homeostasis. Proton-coupled folate transporter (PCFT) and reduced folate carrier (RFC) are the major folate transporters responsible for folate uptake at basolateral membrane of hepatocytes. Low serum folate levels are frequently associated with obesity. We investigated the mechanism that regulated folate status in a mouse model with diet-induced obesity...
September 4, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30171265/zika-virus-infection-and-implications-for-kidney-disease
#2
REVIEW
Donald J Alcendor
High-level and persistent viruria observed in patients infected by Zika virus (ZIKV) has been well documented. However, renal pathology in acutely infected, immunocompetent patients remains subclinical. Moreover, the long-term impact of ZIKV infection, replication, and persistence in the renal compartment of adults and infants as well as immunosuppressed patients and solid organ transplant (SOT) recipients is unknown. Mechanisms involving host and viral factors that limit or control ZIKV pathogenesis in the renal compartment are important yet unexplored...
August 31, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30159587/nlrp3-deficiency-accelerates-pressure-overload-induced-cardiac-remodeling-via-increased-tlr4-expression
#3
Fangfang Li, Hao Zhang, Lu Yang, Hui Yong, Qingqing Qin, Mengtong Tan, Luhong Xu, Kai Liang, Jing Zong, Wenhao Qian
NLRP3, a member of the nucleotide-binding oligomerization domain (NOD)-like receptor family, is involved in cardiac inflammation. However, the functional role of NLRP3 in cardiac remodeling is not clear. To investigate the roles of NLRP3 in pressure overload-induced cardiac remodeling, NLRP3 knockout and wild-type mice were subjected to aortic banding to induce cardiac remodeling. The data showed that NLRP3 expression was downregulated in the remodeling process. NLRP3 deficiency accelerated cardiac hypertrophy, fibrosis, and inflammation responses with deteriorating cardiac dysfunction in the pressure overload-induced cardiac remodeling mouse model...
August 29, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30155768/stimulation-of-angiogenesis-using-single-pulse-low-pressure-shock-wave-treatment
#4
Susinder Sundaram, Karthi Sellamuthu, Krishnaveni Nagavelu, Harikumar R Suma, Arpan Das, Raghu Narayan, Dipshikha Chakravortty, Jagadeesh Gopalan, Sandeep M Eswarappa
Endothelial cells respond to mechanical stimuli such as stretch. This property can be exploited with caution to induce angiogenesis which will have immense potential to treat pathological conditions associated with insufficient angiogenesis. The primary aim of this study is to test if low-pressure shock waves can be used to induce angiogenesis. Using a simple diaphragm-based shock tube, we demonstrate that a single pulse of low pressure (0.4 bar) shock wave is enough to induce proliferation in bovine aortic endothelial cells and human pulmonary microvascular endothelial cells...
August 28, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30008018/plasma-micrornas-as-biomarkers-for-lamin-a-c-related-dilated-cardiomyopathy
#5
Rocío Toro, Sara Blasco-Turrión, Francisco José Morales-Ponce, Pablo Gonzalez, Pablo Martínez-Camblor, Amador López-Granados, Ramon Brugada, Oscar Campuzano, Alexandra Pérez-Serra, Felix Rosa Longobardo, Alipio Mangas, Vicenta Llorente-Cortes, David de Gonzalo-Calvo
Lamin A/C gene (LMNA)-related familial dilated cardiomyopathy (fDCM) is an aggressive heart disease that often leads to transplantation and sudden death. The aim of our study was to evaluate the circulating microRNA (miRNA) profiles of patients with LMNA pathogenic mutations. The study population (N = 75) included (i) patients with pathogenic LMNA mutations responsible for fDCM (LMNAMUT ), (ii) age- and sex-matched LMNA wild-type controls (LMNAWT control), and (iii) LMNA wild-type idiopathic DCM (iDCM) patients (LMNAWT iDCM)...
July 14, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30003291/epigenetic-regulation-of-toll-like-receptors-and-its-roles-in-type-1-diabetes
#6
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
#7
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/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/30151738/dietary-phytol-reduces-clinical-symptoms-in-experimental-autoimmune-encephalomyelitis-eae-at-least-partially-by-modulating-nox2-expression
#9
Leonard Blum, Nadja Tafferner, Ilknur Spring, Jennifer Kurz, Natasja deBruin, Gerd Geisslinger, Michael J Parnham, Susanne Schiffmann
Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system. We investigated the effect of phytol in an animal model of MS, experimental autoimmune encephalomyelitis (EAE), as phytol, a plant-derived diterpene alcohol, exerts anti-inflammatory and redox-protective actions. We observed a significant amelioration of clinical symptoms in EAE C57BL/6N mice fed prophylactically with a phytol-enriched diet. Demyelination, DNA damage, and infiltration of immune cells, specifically TH 1 cells, into the central nervous system were reduced in phytol-fed EAE mice...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30140938/microrna-675-cooperates-pkm2-to-aggravate-progression-of-human-liver-cancer-stem-cells-induced-from-embryonic-stem-cells
#10
Yuxin Yang, Qiuyu Meng, Chen Wang, Xiaonan Li, Yanan Lu, Xiaoru Xin, Qidi Zheng, Dongdong Lu
Both miR675 and pyruvate kinase M2 (PKM2) contribute to malignant progression of tumor, but its functions in liver cancer stem cells remain unclear. Herein, our findings indicate that miR675 plus PKM2 strongly promotes the growth of liver cancer stem cells. Mechanistically, miR675 plus PKM2 enhances the transcriptional activity of SUV39h2. On the other hand, the excessive SUV39h2 binds to more substrate histone H3, triggering an increase of tri-methylation of histone H3 on the ninth lysine. Furthermore, the tri-methylation of histone 3 on the ninth lysine (H3K9me3)-heterochromatin protein 1 alpha (HP1α) complex is increased when the complex occupancy ability on the C-myc promoter region is raised, recruiting CREB, P300, and RNApolII to the special position that results in C-myc high abundance...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30128729/translating-emerging-molecular-genetic-insights-into-clinical-practice-in-inherited-cardiomyopathies
#11
REVIEW
Babken Asatryan, Argelia Medeiros-Domingo
Cardiomyopathies are primarily genetic disorders of the myocardium associated with higher risk of life-threatening cardiac arrhythmias, heart failure, and sudden cardiac death. The evolving knowledge in genomic medicine during the last decade has reshaped our understanding of cardiomyopathies as diseases of multifactorial nature and complex pathophysiology. Genetic testing in cardiomyopathies has subsequently grown from primarily a research tool into an essential clinical evaluation piece with important clinical implications for patients and their families...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30109367/regulation-of-il-1-signaling-by-the-decoy-receptor-il-1r2
#12
REVIEW
Thomas Schlüter, Carsten Schelmbauer, Khalad Karram, Ilgiz A Mufazalov
The pleiotropic cytokine IL-1 mediates its biological functions via association with the signaling receptor IL-1R1. Despite an apparent simplicity in IL-1 signaling activation, multiple negative regulators have been identified. The decoy receptor IL-1R2 (also known as CD121b) can suppress IL-1 maturation, sequester its active forms or hinder the signaling complex assembly. IL-1R2 is differentially expressed among numerous cell types and displays cis- and trans- modes of action. In this review, we link different forms of IL-1R2 (membrane-bound (mIL-1R2), secreted (sIL-1R2), shedded (shIL-1R2), cytoplasmic, and intracellular domain (IL-1R2ICD ) restricted) with their ability to interfere with IL-1, thereby regulating immune responses...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30105447/cell-specific-gene-therapy-driven-by-an-optimized-hypoxia-regulated-vector-reduces-choroidal-neovascularization
#13
Manas R Biswal, Howard M Prentice, George W Smith, Ping Zhu, Yao Tong, C Kathleen Dorey, Alfred S Lewin, Janet C Blanks
Aberrant growth of blood vessels in the choroid layer of the eye, termed choroidal neovascularization (CNV), is the pathological hallmark of exudative age-related macular degeneration (AMD), causing irreversible blindness among the elderly. Co-localization of proangiogenic factors and hypoxia inducible factors (HIF) in neovascular membranes from AMD eyes suggests the role of hypoxia in pathogenesis of CNV. In order to utilize hypoxic conditions in RPE for therapeutic purposes, we developed an optimized hypoxia regulated, RPE cell-specific gene therapy to inhibit choroidal neovascularization...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30097674/oxidative-stress-induced-mirnas-modulate-akt-signaling-and-promote-cellular-senescence-in-uterine-leiomyoma
#14
Xiuhua Xu, J Julie Kim, Yinuo Li, Jia Xie, Changshun Shao, Jian-Jun Wei
Uterine leiomyomas (ULM) grow under high oxidative stress due to a hypoxic microenvironment and defects in redox metabolism. AKT is one major pathway activated by reactive oxygen species (ROS) that maintains ULM growth and survival. We previously reported that AKT inactivated by AKT inhibitors can significantly induce cellular senescence in ULM cells. Since some miRNAs are induced by AKT inhibitors in an ROS-dependent manner, we proposed that these miRNAs may modulate AKT function and cellular senescence in ULM...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30090948/interferon-gamma-decreases-intestinal-epithelial-aquaporin-3-expression-through-downregulation-of-constitutive-transcription
#15
Michael A Peplowski, Michael Dicay, Cristiane H Baggio, Filip Wysokinski, Bernard Renaux, Morley D Hollenberg, David Proud, Wallace K MacNaughton
Aquaporin (AQP) 3 expression is altered in inflammatory bowel diseases, although the exact mechanisms regulating AQP abundance are unclear. Although interferon gamma (IFNγ) is centrally involved in intestinal inflammation, the effect of this cytokine on AQP3 expression remains unknown. HT-29 human colonic epithelial cells were treated with IFNγ to assess AQP3 mRNA expression by real-time RT-PCR and functional protein expression through the uptake of radiolabelled glycerol. Transient knockdown of signal transducer and activator of transcription 1 (STAT1), STAT3, Sp1, and Sp3 were performed to determine the involvement of these transcription factors in the IFNγ-induced signalling cascade...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30088035/stim1-deficiency-is-linked-to-alzheimer-s-disease-and-triggers-cell-death-in-sh-sy5y-cells-by-upregulation-of-l-type-voltage-operated-ca-2-entry
#16
Carlos Pascual-Caro, Maria Berrocal, Aida M Lopez-Guerrero, Alberto Alvarez-Barrientos, Eulalia Pozo-Guisado, Carlos Gutierrez-Merino, Ana M Mata, Francisco Javier Martin-Romero
STIM1 is an endoplasmic reticulum protein with a role in Ca2+ mobilization and signaling. As a sensor of intraluminal Ca2+ levels, STIM1 modulates plasma membrane Ca2+ channels to regulate Ca2+ entry. In neuroblastoma SH-SY5Y cells and in familial Alzheimer's disease patient skin fibroblasts, STIM1 is cleaved at the transmembrane domain by the presenilin-1-associated γ-secretase, leading to dysregulation of Ca2+ homeostasis. In this report, we investigated expression levels of STIM1 in brain tissues (medium frontal gyrus) of pathologically confirmed Alzheimer's disease patients, and observed that STIM1 protein expression level decreased with the progression of neurodegeneration...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30088034/genetic-ablation-of-adenosine-receptor-a3-results-in-articular-cartilage-degeneration
#17
Ruzanna Shkhyan, Siyoung Lee, Francesca Gullo, Lei Li, Maria Peleli, Mattias Carlstrom, Andrei S Chagin, Nicholas W Banks, Sean Limfat, Nancy Q Liu, Denis Evseenko
Osteoarthritis (OA), the most common form of arthritis, is characterized by inflammation of joints and cartilage degradation leading to disability, discomfort, severe pain, inflammation, and stiffness of the joint. It has been shown that adenosine, a purine nucleoside composed of adenine attached to ribofuranose, is enzymatically produced by the human synovium. However, the functional significance of adenosine signaling in homeostasis and pathology of synovial joints remains unclear. Adenosine acts through four cell surface receptors, i...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30073573/tumor-necrosis-factor-tnf-modulates-synaptic-plasticity-in-a-concentration-dependent-manner-through-intracellular-calcium-stores
#18
Nicola Maggio, Andreas Vlachos
The role of inflammatory signaling pathways in synaptic plasticity has long been identified. Yet, it remains unclear how inflammatory cytokines assert their pleiotropic effects on neural plasticity. Moreover, the neuronal targets through which inflammatory cytokines assert their effects on plasticity remain not well-understood. In an attempt to learn more about the plasticity-modulating effects of the pro-inflammatory cytokine tumor necrosis factor (TNF), we used two-pathway long-term potentiation (LTP) experiments at Schaffer collateral-CA1 synapses to test for concentration-dependent effects of TNF on synaptic plasticity...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30069746/low-cleaved-caspase-7-levels-indicate-unfavourable-outcome-across-all-breast-cancers
#19
Andreas U Lindner, Federico Lucantoni, Damir Varešlija, Alexa Resler, Brona M Murphy, William M Gallagher, Arnold D K Hill, Leonie S Young, Jochen H M Prehn
Elevated levels of the anti-apoptotic BCL2 protein associate with favourable outcome in breast cancer. We investigated whether executioner caspase activation downstream of mitochondrial apoptosis was associated with, or independent, of BCL2's prognostic signature in breast cancer. Levels of pro- and anti-apoptotic BCL2 family proteins were quantified in triple negative breast cancer (TNBC) samples and utilised to calculate BCL2 profiles of 845 breast cancer patients. Biomarkers including single apoptosis proteins and network-enriched apoptosis system signatures were evaluated using uni- and multi-variate Cox-models...
October 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/30069747/adenosinergic-signaling-as-a-target-for-natural-killer-cell-immunotherapy
#20
REVIEW
Jiao Wang, Sandro Matosevic
Purinergic signaling through adenosine plays a key role in immune regulation. Hypoxia-driven accumulation of extracellular adenosine results in the generation of an immunosuppressive niche that fuels tumor development. Such immunometabolic modulation has shown to be a promising therapeutic target through blockade of adenosine receptors which mediate adenosine's immunosuppressive function, or cancer-associated ectonucleotidases CD39 and CD73 that catalyze the synthesis of adenosine. Adenosinergic signaling heavily implicates natural killer cells through both direct and indirect effects on their cytolytic activity, expression of cytotoxic granules, interferon-γ, and activating receptors...
September 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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