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https://www.readbyqxmd.com/read/29349588/amphiregulin-enhances-cardiac-fibrosis-and-aggravates-cardiac-dysfunction-in-mice-with-experimental-myocardial-infarction-partly-through-activating-egfr-dependent-pathway
#1
Liang Liu, Xian Jin, Cui-Fen Hu, Ya-Ping Zhang, Zhong'e Zhou, Rong Li, Cheng-Xing Shen
Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF) post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several organs. However, the expression of AR and its role post-MI are yet to be determined. This study aimed to investigate the impact of AR on CF post-MI and related mechanisms. Significantly upregulated AR expression was evidenced in the infarct border zone of MI mice in vivo and the AR secretion was enhanced in macrophages, but not in cardiac fibroblasts...
January 18, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29344510/ablation-of-fgfr2-in-fibroblasts-ameliorates-kidney-fibrosis-after-ischemia-reperfusion-injury-in-mice
#2
Zhuo Xu, Chunsun Dai
Background: Fibroblast growth factors (FGFs) are heparin-binding proteins involved in a variety of biological processes. However, the role and mechanisms of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further investigation. Methods: In this study, a mouse model with fibroblast-specific FGFR2 gene disruption was generated. The knockouts were born normal and no kidney dysfunction or histological abnormality was found within 2 months after birth...
December 2017: Kidney Diseases
https://www.readbyqxmd.com/read/29343458/right-ventricular-fibrosis-and-dysfunction-actual-concepts-and-common-misconceptions
#3
REVIEW
Bakytbek Egemnazarov, Slaven Crnkovic, Bence M Nagy, Horst Olschewski, Grazyna Kwapiszewska
Fibrosis and remodeling of the right ventricle (RV) are associated with RV dysfunction and mortality of patients with pulmonary hypertension (PH) but it is unknown how much RV fibrosis contributes to RV dysfunction and mortality. RV fibrosis manifests as fibroblast accumulation and collagen deposition which may be excessive. Although extracellular matrix deposition leads to elevated ventricular stiffness, it is not known to which extent it affects RV function. Various animal models of pulmonary hypertension have been established to investigate the role of fibrosis in RV dysfunction and failure...
January 14, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29339450/cardiac-macrophages-promote-diastolic-dysfunction
#4
Maarten Hulsmans, Hendrik B Sager, Jason D Roh, María Valero-Muñoz, Nicholas E Houstis, Yoshiko Iwamoto, Yuan Sun, Richard M Wilson, Gregory Wojtkiewicz, Benoit Tricot, Michael T Osborne, Judy Hung, Claudio Vinegoni, Kamila Naxerova, David E Sosnovik, Michael R Zile, Amy D Bradshaw, Ronglih Liao, Ahmed Tawakol, Ralph Weissleder, Anthony Rosenzweig, Filip K Swirski, Flora Sam, Matthias Nahrendorf
Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in humans and mice with diastolic dysfunction, which in mice was induced by either hypertension or advanced age. A higher murine myocardial macrophage density results from monocyte recruitment and increased hematopoiesis in bone marrow and spleen...
January 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29331958/platelet-secretion-defects-and-acquired-von-willebrand-syndrome-in-patients-with-ventricular-assist-devices
#5
Ulrich Geisen, Kerstin Brehm, Georg Trummer, Michael Berchtold-Herz, Claudia Heilmann, Friedhelm Beyersdorf, Johannes Schelling, Axel Schlagenhauf, Barbara Zieger
BACKGROUND: The number of implanted ventricular assist devices (VADs) has increased significantly recently. Bleeding, the most frequent complication, cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD featuring potential improvements over the HeartMate II. METHODS AND RESULTS: In this study, we investigated the prevalence and onset of AVWS in 198 VAD patients...
January 13, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29327586/composite-hydrogel-modified-by-igf-1c-domain-improves-stem-cell-therapy-for-limb-ischemia
#6
Xiaomin Wang, Jimin Zhang, Weilong Cui, Yuan Fang, Li Li, Shenglu Ji, Duo Mao, Tingyu Ke, Xin Yao, Dan Ding, Guowei Feng, Deling Kong
Stem cell treatment for critical limb ischemia yields a limited therapeutic effect due to cell loss and dysfunction caused by local ischemic environment. Biomimetic scaffolds emerge as ideal cell delivery vehicles for regulating cell fate via mimicking the components of stem cell niche. Herein, we prepared a bioactive hydrogel by mixing chitosan and hyaluronic acid that is immobilized with C domain peptide of IGF-1 (IGF-1C), and examined whether this hydrogel could augment stem cell survival and therapeutic potential...
January 12, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29326176/combinatorial-omics-analysis-reveals-perturbed-lysosomal-homeostasis-in-collagen-vii-deficient-keratinocytes
#7
Kerstin Thriene, Björn Andreas Grüning, Olivier Bornert, Anika Erxleben, Juna Leppert, Ioannis Athanasiou, Ekkehard Weber, Dimitra Kiritsi, Alexander Nyström, Thomas Reinheckel, Rolf Backofen, Cristina Has, Leena Bruckner-Tuderman, Joern Dengjel
The extracellular matrix protein collagen VII is part of the microenvironment of stratified epithelia and critical in organismal homeostasis. Mutations in the encoding gene COL7A1 lead to the skin disorder dystrophic epidermolysis bullosa (DEB), are linked to skin fragility and progressive inflammation-driven fibrosis that facilitates aggressive skin cancer. So far, these changes have been linked to mesenchymal alterations, the epithelial consequences of collagen VII loss remaining under-addressed. As epithelial dysfunction is a principal initiator of fibrosis, we performed a comprehensive transcriptome and proteome profiling of primary human keratinocytes to generate global and detailed images of dysregulated epidermal molecular pathways linked to loss of collagen VII...
January 11, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29325930/integrated-study-on-comparative-transcriptome-and-skeletal-muscle-function-in-aged-rats
#8
Jing Zhou, Zhiyin Liao, Jinliang Chen, Kexiang Zhao, Qian Xiao
The present study aimed to reveal aging-related changes in the skeletal muscle of SD rats by comparing transcriptome analysis, integrated with muscle physiological parameters. Ten rats aged 25 months were set as the old group (OG) and ten rats aged 6 months were set as the young group (YG). After 6 weeks of feeding, the body mass, grip strength, and gastrocnemius muscle mass were determined, and the differentially expressed genes were analyzed by transcriptome sequencing, followed by GO enrichment analysis and KEGG analysis...
January 8, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29320534/the-endothelial-specific-isoform-of-type-xviii-collagen-correlates-to-annual-bleeding-rate-in-haemophilia-patients
#9
Nadja Gad Kjeld, Baolai Hua, Morten Asser Karsdal, Shu Sun, Tina Manon-Jensen
INTRODUCTION: The medical need in the haemophilic (HF) field to reduce bleeding incidents requires measurement of the annual bleeding rate (ABR) in haemophiliacs. Vascular rupture is associated with damage to the vascular endothelium causing exposure of the basement membrane. Endothelial cells and matrix impairment may be associated with joint bleeds and later development of HF arthropathy. Imbalanced extracellular matrix turnover is a central pathological feature in many diseases consequent to epithelial or endothelial cell damage...
2018: PloS One
https://www.readbyqxmd.com/read/29313089/first-delivery-and-ovariectomy-affect-biomechanical-and-structural-properties-of-the-vagina-in-the-ovine-model
#10
Iva Urbankova, Geertje Callewaert, Silvia Blacher, Dries Deprest, Lucie Hympanova, Andrew Feola, Laurent De Landsheere, Jan Deprest
INTRODUCTION AND HYPOTHESIS: Animal models are useful for investigating the genesis of pelvic floor dysfunction and for developing novel therapies for its treatment. There is a need for an alternative large-animal model to the nonhuman primate. Therefore we studied the effects of the first vaginal delivery, ovariectomy and systemic hormonal replacement therapy (HRT) on the biomechanical and structural properties of the ovine vagina. METHODS: We examined the gross anatomical properties of nulliparous, primiparous, ovariectomized multiparous, and ovariectomized hormone-replaced multiparous sheep (six animals per group)...
January 8, 2018: International Urogynecology Journal
https://www.readbyqxmd.com/read/29305555/impaired-lymphoid-extracellular-matrix-impedes-antibacterial-immunity-in-epidermolysis-bullosa
#11
Alexander Nyström, Olivier Bornert, Tobias Kühl, Christine Gretzmeier, Kerstin Thriene, Jörn Dengjel, Andrea Pfister-Wartha, Dimitra Kiritsi, Leena Bruckner-Tuderman
Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB), a skin fragility disorder that, unexpectedly, manifests also with elevated colonization of commensal bacteria and frequent wound infections. Here, we describe an unprecedented systemic function of collagen VII as a member of a unique innate immune-supporting multiprotein complex in spleen and lymph nodes. In this complex, collagen VII specifically binds and sequesters the innate immune activator cochlin in the lumen of lymphoid conduits...
January 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29304151/the-role-of-carboxy-terminal-cross-linking-telopeptide-of-type-i-collagen-dual-x-ray-absorptiometry-bone-strain-and-romberg-test-in-a-new-osteoporotic-fracture-risk-evaluation-a-proposal-from-an-observational-study
#12
Fabio M Ulivieri, Luca P Piodi, Enzo Grossi, Luca Rinaudo, Carmelo Messina, Anna P Tassi, Marcello Filopanti, Anna Tirelli, Francesco Sardanelli
The consolidated way of diagnosing and treating osteoporosis in order to prevent fragility fractures has recently been questioned by some papers, which complained of overdiagnosis and consequent overtreatment of this pathology with underestimating other causes of the fragility fractures, like falls. A new clinical approach is proposed for identifying the subgroup of patients prone to fragility fractures. This retrospective observational study was conducted from January to June 2015 at the Nuclear Medicine-Bone Metabolic Unit of the of the Fondazione IRCCS Ca' Granda, Milan, Italy...
2018: PloS One
https://www.readbyqxmd.com/read/29300224/achilles-tendinopathy
#13
Umile Giuseppe Longo, Mario Ronga, Nicola Maffulli
Achilles tendinopathy is a common cause of disability. Despite the economic and social relevance of the problem, the causes and mechanisms of Achilles tendinopathy remain unclear. Tendon vascularity, gastrocnemius-soleus dysfunction, age, sex, body weight and height, pes cavus, and lateral ankle instability are considered common intrinsic factors. The essence of Achilles tendinopathy is a failed healing response, with haphazard proliferation of tenocytes, some evidence of degeneration in tendon cells and disruption of collagen fibers, and subsequent increase in noncollagenous matrix...
March 2018: Sports Medicine and Arthroscopy Review
https://www.readbyqxmd.com/read/29298467/impact-of-preoperative-patient-characteristics-and-flow-rate-on-failure-early-complications-and-voiding-dysfunction-after-a-transobturator-tape-procedure-a-multicentre-study
#14
Andrea Cocci, Giovanni E Cacciamani, Giorgio Ivan Russo, Maria Angela Cerruto, Martina Milanesi, Luis G Medina, Sebastiano Cimino, Walter Artibani, Giuseppe Morgia, Marco Carini, Vincenzo Li Marzi
PURPOSE: To evaluate the impact of preoperative patient characteristics and flow rate on failure, early postoperative complications, and voiding in patients who underwent transvaginal tension-free vaginal tape-obturator (TVT-O) treatment for uncomplicated stress urinary incontinence (SUI). METHODS: We retrospectively reviewed patients who underwent TVT-O for SUI at 3 Italian centres. The exclusion criteria were predominant voiding and storage symptoms suggestive of detrusor overactivity, the presence of grade >1 urogenital prolapse, previous pelvic radiotherapy or other clinical contraindications for surgical procedures, neurogenic bladder dysfunction, and collagen diseases...
December 2017: International Neurourology Journal
https://www.readbyqxmd.com/read/29296914/severe-platelet-dysfunction-in-nhl-patients-receiving-ibrutinib-is-absent-in-patients-receiving-acalabrutinib
#15
Alexander P Bye, Amanda J Unsworth, Michael J Desborough, Catherine A T Hildyard, Niamh Appleby, David Bruce, Neline Kriek, Sophie H Nock, Tanya Sage, Craig E Hughes, Jonathan M Gibbins
The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib. The second-generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with non-Hodgkin lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289557/salidroside-attenuates-endothelial-cellular-senescence-via-decreasing-the-expression-of-inflammatory-cytokines-and-increasing-the-expression-of-sirt3
#16
Sha-Sha Xing, Jian Li, Lin Chen, Ya-Fei Yang, Ping-Lin He, Jun Li, Jin Yang
OBJECTIVE: Endothelial cellular senescence is an important contributor to the endothelial dysfunction and atherosclerosis. Our previous studies suggested that salidroside (SAL) can alleviate atherosclerosis and protect endothelial cells against oxidative stress induced damage. However, the effect and mechanism of SAL on endothelial cellular senescence is still unclear. Here, we investigated the underlying mechanisms of SAL on preventing endothelial cellular premature senescence. METHODS AND RESULTS: We established a hyperhomocysteinemia (HHcy)mouse model via high methionine diet (HMD) to explore the protective effect of SAL...
December 28, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29288034/structural-and-functional-remodelling-of-the-atrioventricular-node-with-ageing-in-rats-the-role-of-hyperpolarization-activated-cyclic-nucleotide-gated-and-ryanodine-2-channels
#17
Yawer Saeed, Ian Temple, Zoltan Borbas, Andrew Atkinson, Joseph Yanni, Michal Maczewski, Urszula Mackiewicz, Mariam Aly, Sunil J R J Logantha, Clifford Garratt, Halina Dobrzynski
BACKGROUND: Ageing is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction. OBJECTIVES: The aim of the study is to identify the structural and functional remodelling in the atrioventricular junction (AVJ) with ageing. METHODS: Electrophysiological, histology and immunohistochemistry experiments on male Wistar-Hanover rats aged 3months (n=24) and 2years (n=15) were performed. AH interval, Wenkebach cycle length (WBCL) and AVN effective refractory period (AVNERP) were measured...
December 26, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29286395/benefits-of-cardiac-resynchronization-therapy-in-an-asynchronous-heart-failure-model-induced-by-left-bundle-branch-ablation-and-rapid-pacing
#18
Jingfeng Wang, Zhenning Nie, Haiyan Chen, Xianhong Shu, Zhaohua Yang, Ruiming Yao, Yangang Su, Junbo Ge
It is now well recognized that heart failure (HF) patients with left bundle branch block (LBBB) derive substantial clinical benefits from cardiac resynchronization therapy (CRT), and LBBB has become one of the important predictors for CRT response. The conventional tachypacing-induced HF model has several major limitations, including absence of stable LBBB and rapid reversal of left ventricular (LV) dysfunction after cessation of pacing. Hence, it is essential to establish an optimal model of chronic HF with isolated LBBB for studying CRT benefits...
December 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29284608/melanocortin-1-receptor-deficiency-promotes-atherosclerosis-in-apolipoprotein-e-mice
#19
Petteri Rinne, James J Kadiri, Mauricio Velasco-Delgado, Salla Nuutinen, Miro Viitala, Maija Hollmén, Martina Rami, Eriika Savontaus, Sabine Steffens
OBJECTIVE: The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis...
December 28, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29280493/the-effects-of-concurrent-chemoradiation-therapy-to-the-base-of-tongue-in-a-preclinical-model
#20
Peter A Benedict, Ryan Ruiz, Avanti Verma, Gregory R Dion, Philmo Oh, Binhuan Wang, Omar H Ahmed, Nao Hiwatashi, Renjie Bing, Kristen Victor, Kenneth S Hu, Aaron Johnson, Ryan C Branski, Milan R Amin
OBJECTIVES/HYPOTHESIS: To develop a clinically relevant model of oropharyngeal concurrent chemoradiation therapy (CCRT) in order to quantify the effects of CCRT on tongue function and structure. CCRT for advanced oropharyngeal cancer commonly leads to tongue base dysfunction and dysphagia. However, no preclinical models currently exist to study the pathophysiology of CCRT-related morbidity, thereby inhibiting the development of targeted therapeutics. STUDY DESIGN: Animal model...
December 27, 2017: Laryngoscope
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