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https://www.readbyqxmd.com/read/29780142/diabetes-mellitus-induced-bone-fragility
#1
Ippei Kanazawa, Toshitsugu Sugimoto
Accumulating evidence has shown that the risk of osteoporotic fractures is increased in patients with diabetes mellitus (DM). Thus, DM-induced bone fragility has been recently recognized as a diabetic complication. Because the fracture risk is independent of the reduction in bone mineral density, deterioration of the bone quality may be the main cause of bone fragility. Although its mechanism remains poorly understood, accumulated collagen cross-links of advanced glycation end-products (AGEs) and dysfunctions of osteoblast and osteocyte may be involved...
May 18, 2018: Internal Medicine
https://www.readbyqxmd.com/read/29775412/inhibitor-of-lysyl-oxidase-improves-cardiac-function-and-the-collagen-mmp-profile-in-response-to-volume-overload
#2
Elia C El Hajj, Milad C El Hajj, Van K Ninh, Jason D Gardner
The cardiac extracellular matrix is a complex architectural network that serves many functions including providing structural and biochemical support to surrounding cells, and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of the pro-inflammatory and pro-fibrotic responses induce a vicious cycle which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29769710/jdp2-overexpression-provokes-cardiac-dysfunction-in-mice
#3
Jacqueline Heger, Julia Bornbaum, Alona Würfel, Christian Hill, Nils Brockmann, Renáta Gáspár, János Pálóczi, Zoltán V Varga, Márta Sárközy, Péter Bencsik, Tamás Csont, Szilvia Török, Baktybek Kojonazarov, Ralph Theo Schermuly, Kerstin Böngler, Mariana Parahuleva, Peter Ferdinandy, Rainer Schulz, Gerhild Euler
The transcriptional regulator JDP2 (Jun dimerization protein 2) has been identified as a prognostic marker for patients to develop heart failure after myocardial infarction. We now performed in vivo studies on JDP2-overexpressing mice, to clarify the impact of JDP2 on heart failure progression. Therefore, during birth up to the age of 4 weeks cardiac-specific JDP2 overexpression was prevented by doxycycline feeding in transgenic mice. Then, JDP2 overexpression was started. Already after 1 week, cardiac function, determined by echocardiography, decreased which was also resembled on the cardiomyocyte level...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29767844/comorbidities-associated-with-higher-von-willebrand-factor-vwf-levels-may-explain-the-age-related-increase-of-vwf-in-von-willebrand-disease
#4
Ferdows Atiq, Karina Meijer, Jeroen Eikenboom, Karin Fijnvandraat, Eveline P Mauser-Bunschoten, Karin P M van Galen, Marten R Nijziel, Paula F Ypma, Joke de Meris, Britta A P Laros-van Gorkom, Johanna G van der Bom, Moniek P de Maat, Marjon H Cnossen, Frank W G Leebeek
Some comorbidities, such as hypertension, are associated with higher von Willebrand factor (VWF) levels in the general population. No studies have been conducted to assess this association in patients with von Willebrand disease (VWD). Therefore, we studied this association in patients with type 1 (n = 333) and type 2 (n = 203) VWD from the 'WiN" study. VWF antigen (VWF:Ag) was higher in type 1 VWD patients with hypertension [difference: 0·23 iu/ml, 95% confidence interval (CI): 0·11-0·35], diabetes mellitus (0·11 iu/ml, 95% CI: -0·02 to 0·23), cancer (0·14 iu/ml, 95% CI: 0·03-0·25) and thyroid dysfunction (0·14 iu/ml, 95% CI: 0·03-0·26) than in patients without these comorbidities (all corrected for age, sex and blood group)...
May 16, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29767558/molecular-basis-of-the-counteraction-by-calcium-channel-blockers-of-cyclosporine-nephrotoxicity
#5
Safaa Hicham Hammoud, Sahar Alkhansa, Neamah Mahjoub, Amal Galal Omar, Mahmoud M El-Mas, Assaad A Eid
Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine (CSA). In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorate renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats (n=6/group) were used and received one of the following treatments for 7 consecutive days: vehicle (cremophor EL, i...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29758174/g-protein-coupled-estrogen-receptor-gper-deficiency-induces-cardiac-remodeling-through-oxidative-stress
#6
Hao Wang, Xuming Sun, Marina S Lin, Carlos M Ferrario, Holly Van Remmen, Leanne Groban
Oxidative stress has been implicated in the unfavorable changes in cardiac function and remodeling that occur after ovarian estrogen loss. Using ovariectomized rat models, we previously reported that the cardioprotective actions of estrogen are mediated by the G protein-coupled estrogen receptor (GPER). Here, in 9-month-old, female cardiomyocyte-specific GPER knockout (KO) mice vs sex- and age-matched wild-type (WT) mice, we found increased cardiac oxidative stress and oxidant damage, measured as a decreased ratio of reduced glutathione to oxidized glutathione, increased 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine (8-oxo-DG) staining, and increased expression of oxidative stress-related genes...
April 25, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29753801/a-comparative-study-between-2-different-grafts-used-as-patches-after-plaque-incision-and-inflatable-penile-prosthesis-implantation-for-end-stage-peyronie-s-disease
#7
Marco Falcone, Mirko Preto, Carlo Ceruti, Massimiliano Timpano, Giulio Garaffa, Omidreza Sedigh, Mattia Sibona, Marco Oderda, Paolo Gontero, Luigi Rolle
BACKGROUND: Although many grafts have been used for plaque incision with grafting (PIG) and penile prosthesis (PP) implantation, there is no evidence that favors 1 specific graft over another. AIM: To compare fibrin-coated collagen fleece (TachoSil; Baxter International, Deerfield, IL, USA) with porcine small intestinal submucosa (SIS; Cook Biotech, West Lafayette, IN, USA) as grafts. METHODS: From January 2007 to January 2015, 60 non-randomized consecutive patients affected by end-stage Peyronie disease underwent PIG and PP implantation (AMS 700CX; Boston Scientific, Marlborough, MA, USA)...
May 9, 2018: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29753072/ampk%C3%AE-2-deficiency-exacerbates-long-term-pm-2-5-exposure-induced-lung-injury-and-cardiac-dysfunction
#8
Hongyun Wang, Xiyue Shen, Guoxiong Tian, Xili Shi, Wei Huang, Yongguang Wu, Lei Sun, Can Peng, Shasha Liu, Ying Huang, Xiaoyu Chen, Fang Zhang, Yingjie Chen, Wenjun Ding, Zhongbing Lu
Previous studies have demonstrated that long-term exposure to fine particulate matter (PM2.5 ) increases the risk of respiratory and cardiovascular diseases. As a metabolic sensor, AMP-activated protein kinase (AMPK) is a promising target for cardiovascular disease. However, the impact of AMPK on the adverse health effects of PM2.5 has not been investigated. In this study, we exposed wild-type (WT) and AMPKα2-/- mice to either airborne PM2.5 (mean daily concentration ~64µg/m3 ) or filtered air for 6 months through a whole-body exposure system...
May 9, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29750297/col2a1-mutation-c-3508g-a-leads-to-avascular-necrosis-of-the-femoral-head-in-a-chinese-family-a-case-report
#9
Fang Liu, Zhizheng Xiong, Qi Liu, Jinxi Hu, Wenhua Li, Na Zhang
Avascular necrosis of the femoral head (ANFH) is a consequence of ischemia. Although the majority of cases of ANFH are sporadic, certain familial cases of ANFH have been reported to be associated with collagen type II α1 chain (COL2A1) mutations, which lead to COL2A1 gene dysfunction. The structure of secreted type II collagen contains a core area with a triple helical glycine (Gly)‑X‑Y domain, and the replacement of Gly in this region as a result of COL2A1 mutations may damage the structure of type II collagen...
May 7, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29748291/microrna-129-and-335-promote-diabetic-wound-healing-by-inhibiting-sp1-mediated-mmp-9-expression
#10
Wei Wang, Chuan Yang, Xiao Yi Wang, Li Yan Zhou, Guo Juan Lao, Dan Liu, Chuan Wang, Meng Die Hu, Ting Ting Zeng, Li Yan, Meng Ren
Diabetic wounds are recalcitrant to healing. However, the mechanism causing this dysfunction is not fully understood. High expression of matrix metalloproteinase-9 (MMP-9) is indicative of poor wound healing. Here, we show that specificity protein-1 (Sp1), a regulator of MMP-9, binds directly to its promoter and enhances its expression. Additionally, we demonstrated that Sp1 is the direct target of two miRNAs, miR-129 and -335, which are significantly downregulated in diabetic skin tissues. In vitro experiments confirmed that miR-129 or -335 overexpression inhibits MMP-9 promoter activity and protein expression by targeting Sp1, whereas the inhibition of these miRNAs has the opposite effect...
May 10, 2018: Diabetes
https://www.readbyqxmd.com/read/29748247/reduced-levels-of-stromal-sex-hormone-binding-globulin-and-androgen-receptor-dysfunction-in-the-sperm-storage-region-of-the-rat-epididymis
#11
Fabiane de Santi, Flávia L Beltrame, Barry T Hinton, Paulo S Cerri, Estela Sasso-Cerri
The cauda epididymidis is the major sperm storage region whose androgenic supply, essential for the sperm viability, is provided by the vasculature and is dependent upon testosterone diffusion through the stromal tissue to reach the epithelial cells. We have focused our efforts on examining the regulation of this important epididymal region by evaluating the impact of the androgen disrupter cimetidine on the epithelial-stromal androgenic microenvironment. Male rats received 100 mg/kg cimetidine (CMTG) or saline (CG) for 50 days, serum testosterone levels were measured and the epididymal cauda region was processed for light and transmission electron microscopy...
June 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29747275/-the-mechanism-of-nicotine-on-human-bronchial-smooth-muscle-cell-contraction
#12
W Hong, B W Hao, F Peng, G Y Peng, L M Huang, J Xu, W T Cao, B L Liao, L H Tang, J D Pu, B Li, P X Ran
Objective: To investigate the molecular mechanism of contractility dysfunction of human bronchial smooth muscle cells induced by nicotine. Methods: Primary human bronchial smooth muscle cells were cultured in vitro. The cells were divided into a control group and a nicotine group which was treated with 10(-5) mol/L nicotine for 48 h and transfected with or without α7nAChR-siRNA (The siNC group, siNC + nicotine group and siα7nAChR + nicotine group). The effects of nicotine on the cell contractile function were examined by collagen gel shrinkage assay...
May 12, 2018: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/29745022/restoring-mitochondrial-dna-copy-number-preserves-mitochondrial-function-and-delays-vascular-aging-in-mice
#13
Kirsty Foote, Johannes Reinhold, Emma P K Yu, Nichola L Figg, Alison Finigan, Michael P Murphy, Martin R Bennett
Aging is the largest risk factor for cardiovascular disease, yet the molecular mechanisms underlying vascular aging remain unclear. Mitochondrial DNA (mtDNA) damage is linked to aging, but whether mtDNA damage or mitochondrial dysfunction is present and directly promotes vascular aging is unknown. Furthermore, mechanistic studies in mice are severely hampered by long study times and lack of sensitive, repeatable and reproducible parameters of arterial aging at standardized early time points. We examined the time course of multiple invasive and noninvasive arterial physiological parameters and structural changes of arterial aging in mice, how aging affects vessel mitochondrial function, and the effects of gain or loss of mitochondrial function on vascular aging...
May 9, 2018: Aging Cell
https://www.readbyqxmd.com/read/29741626/functional-analysis-of-a-hypomorphic-allele-shows-that-mmp14-catalytic-activity-is-the-prime-determinant-of-the-winchester-syndrome-phenotype
#14
Ivo J H M de Vos, Evelyn Yaqiong Tao, Sheena Li Ming Ong, Julian L Goggi, Thomas Scerri, Gabrielle R Wilson, Chernis Guai Mun Low, Arnette Shi Wei Wong, Dominic Grussu, Alexander P A Stegmann, Michel van Geel, Renske Janssen, David J Amor, Melanie Bahlo, Norris R Dunn, Thomas J Carney, Paul J Lockhart, Barry J Coull, Maurice A M van Steensel
Winchester syndrome (WS, MIM #277950) is an extremely rare autosomal recessive skeletal dysplasia characterized by progressive joint destruction and osteolysis. To date, only one missense mutation in MMP14, encoding the membrane-bound matrix metalloprotease 14, has been reported in WS patients. Here, we report a novel hypomorphic MMP14 p.Arg111His (R111H) allele, associated with a mitigated form of WS. Functional analysis demonstrated that this mutation, in contrast to previously reported human and murine MMP14 mutations, does not affect MMP14's transport to the cell membrane...
May 8, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29740846/prostatic-collagen-architecture-in-neutered-and-intact-canines
#15
Hannah Ruetten, Kyle A Wegner, Michael F Romero, Michael W Wood, Paul C Marker, Douglas Strand, Sara A Colopy, Chad M Vezina
BACKGROUND: Prostate stiffness and increased collagen content both associate with the presence of urinary symptoms in men but mechanisms responsible, including impact of age and androgens, are unknown. Dogs develop prostate-related urinary dysfunction similar to humans, but mechanisms are also unknown. Mice have been used to examine how prostatic collagen accumulation affects voiding but whether mouse prostatic collagen organization resembles human or dog has not been evaluated. Here, we have constructed the first comprehensive, comparative maps of collagen architecture in canine, human, and mouse prostate and test whether canine prostatic collagen content is increased by aging and reduced by castration...
May 8, 2018: Prostate
https://www.readbyqxmd.com/read/29737246/role-of-ox-ldl-and-lox-1-in-atherogenesis
#16
Ajoe John Kattoor, Sri Harsha Kanuri, Jawahar L Mehta
Oxidized LDL (ox-LDL) plays a central role in atherosclerosis by acting on multiple cells such as endothelial cells, macrophages, platelets, fibroblasts and smooth muscle cells through LOX-1. LOX-1 is a 50 kDa transmembrane glycoprotein that serves as receptor for ox-LDL, modified lipoproteins, activated platelets and advance glycation end-products. Ox-LDL through LOX-1, in endothelial cells, cause increase in leukocyte adhesion molecules, activates pathways of apoptosis, increase reactive oxygen species and cause endothelial dysfunction...
May 7, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29732984/knockout-of-trpv1-exacerbates-left-ventricular-diastolic-dysfunction-induced-by-a-high-fat-diet-in-mice
#17
Beihua Zhong, Jack Rubinstein, Shuangtao Ma, Donna H Wang
BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) channels in sensory nerves have anti-oxidative properties and counteract obesity and diabetes that are associated with diastolic dysfunction with preserved ejection fraction. We tested the hypothesis that TRPV1 knockout exacerbates high-fat diet (HFD)-induced glucose intolerance and diastolic dysfunction. METHOD: Trpv1-/- and wild-type (WT) mice were fed chow diet or HFD for 20 weeks. Then, we performed the intraperitoneal glucose tolerance test, measured the heart function through transthoracic echocardiography and Langendorff heart perfusion system, analyzed cardiac histology, and measured the myocardial superoxide production and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases...
May 3, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29731719/rhace2-therapy-modifies-bleomycin-induced-pulmonary-hypertension-via-rescue-of-vascular-remodeling
#18
Anandharajan Rathinasabapathy, Andrew J Bryant, Toshio Suzuki, Christy Moore, Sheila Shay, Santhi Gladson, James D West, Erica J Carrier
Background: Pulmonary hypertension (PH) is a progressive cardiovascular disease, characterized by endothelial and smooth muscle dysfunction and vascular remodeling, followed by right heart failure. Group III PH develops secondarily to chronic lung disease such as idiopathic pulmonary fibrosis (IPF), and both hastens and predicts mortality despite of all known pharmacological interventions. Thus, there is urgent need for development of newer treatment strategies. Objective: Angiotensin converting enzyme 2 (ACE2), a member of the renin angiotensin family, is therapeutically beneficial in animal models of pulmonary vascular diseases and is currently in human clinical trials for primary PH...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29727629/losartan-prevents-the-imbalance-between-renal-dopaminergic-and-renin-angiotensin-systems-induced-by-fructose-overload-l-dopa-dopamine-index-as-new-potential-biomarker-of-renal-dysfunction
#19
Natalia Lucía Rukavina Mikusic, Nicolás Martín Kouyoumdzian, Ana Uceda, Julieta Sofía Del Mauro, Marcela Pandolfo, Mariela Mercedes Gironacci, Ana María Puyó, Jorge Eduardo Toblli, Belisario Enrique Fernández, Marcelo Roberto Choi
BACKGROUND: The renin angiotensin system (RAS) and the renal dopaminergic system (RDS) act as autocrine and paracrine systems to regulate renal sodium management and inflammation and their alterations have been associated to hypertension and renal damage. Nearly 30-50% of hypertensive patients have insulin resistance (IR), with a strong correlation between hyperinsulinemia and microalbuminuria. OBJECTIVE: The aim of this study was to demonstrate the existence of an imbalance between RAS and RDS associated to IR, hypertension and kidney damage induced by fructose overload (FO), as well as to establish their prevention, by pharmacological inhibition of RAS with losartan...
May 1, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29709099/biomarker-based-phenotyping-of-myocardial-fibrosis-identifies-patients-with-heart-failure-with-preserved-ejection-fraction-resistant-to-the-beneficial-effects-of-spironolactone-results-from-the-aldo-dhf-trial
#20
Susana Ravassa, Tobias Trippel, Doris Bach, Diana Bachran, Arantxa González, Begoña López, Rolf Wachter, Gerd Hasenfuss, Christian Delles, Anna F Dominiczak, Burkert Pieske, Javier Díez, Frank Edelmann
BACKGROUND: Myocardial fibrosis is characterized by excessive cross-linking and deposition of collagen type I and is involved in left ventricular stiffening and left ventricular diastolic dysfunction (LVDD). We investigated whether the effect of spironolactone on LVDD in patients with heart failure with preserved ejection fraction (HFpEF) depends on its effects on collagen cross-linking and/or deposition. METHODS AND RESULTS: We investigated 381 HFpEF patients from the multicentre, randomized, placebo-controlled Aldo-DHF trial with measures of the E:e' ratio...
April 30, 2018: European Journal of Heart Failure
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