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https://www.readbyqxmd.com/read/29667905/essential-role-of-mohawk-for-tenogenic-tissue-homeostasis-including-spinal-disc-and-periodontal-ligament
#1
Ryo Nakamichi, Kensuke Kataoka, Hiroshi Asahara
Tendons and ligaments play essential roles in connecting muscle and bone and stabilizing the connections between bones. The damage to tendons and ligaments caused by aging, injury, and arthritis induces the dysfunction of the musculoskeletal system and reduces the quality of life. Current therapy for damaged tendons and ligaments depends on self-repair; however, it is difficult to reconstruct normal tissue. Regeneration therapy for tendons and ligaments has not been achieved, partly because the mechanism, cell biology, and pathophysiology of tendon and ligament development remain unclear...
April 18, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29667769/targeting-the-phosphatidylinositol-3-kinase-akt-mechanistic-target-of-rapamycin-signaling-pathway-in-b-lineage-acute-lymphoblastic-leukemia-an-update
#2
REVIEW
Carolina Simioni, Alberto M Martelli, Giorgio Zauli, Marco Vitale, James A McCubrey, Silvano Capitani, Luca M Neri
Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease...
April 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29667730/succinate-decreases-bladder-function-in-a-rat-model-associated-with-metabolic-syndrome
#3
Monica Velasquez Flores, Abubakr H Mossa, Philippe Cammisotto, Lysanne Campeau
AIMS: Succinate and its receptor, GPR91, have been implicated in different aspects of metabolic syndrome. As GPR91 is expressed in the urinary bladder, the aim of this study is to show the effect of chronically increased succinate levels on bladder function. MATERIALS AND METHODS: Healthy Sprague-Dawley (SD) rats and hypertensive Dahl rats received an intraperitoneal injection of either saline or succinate (50 mg/kg) daily for a period of 4 weeks. Conscious cystometry was performed at the end of this period...
April 18, 2018: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29667585/recent-developments-in-the-diagnosis-and-therapy-of-well-differentiated-neuroendocrine-tumours
#4
J Hofland, R A Feelders, T Brabander, G J H Franssen, W W de Herder
Well-differentiated neuroendocrine tumours (NETs) of the digestive tract are being increasingly detected, which is partly explained by the increased use of endoscopic and cross-sectional imaging as well as improved recognition at histopathological evaluation. After the discovery of this relatively indolent type of epithelial malignancy over 100 years ago, their sporadic occurrence and divergent biological behaviour at multiple primary sites have hampered dedicated studies into NET pathogenesis and testing of drug efficacy in well-designed clinical trials...
April 2018: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/29667545/molecular-bases-of-sperm-thermotaxis-old-and-new-knowledges
#5
Luca De Toni, Savina Dipresa, Carlo Foresta, Andrea Garolla
Sperm thermotaxis, namely the temperature-oriented motility of sperm cells, is a key process involved in ejaculated sperm guidance towards the oocyte for fertilization pourposes. Since its discovery in 2003, many studies clarified the dynamic, the sensitivity and the overall weight of this process in the comprehensive context of fertilization. However, the identification of sperm thermosensor/s remained elusive until recently. The most recent cues about the molecular bases of the old known process of thermotaxis are here revised...
April 18, 2018: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29667458/sudden-unexpected-death-in-epilepsy-ongoing-challenges-in-finding-mechanisms-and-prevention
#6
Doungporn Ruthirago, Parunyou Julayanont, Amputch Karukote, Mohamed Shehabeldin, Kenneth Nugent
Patients with epilepsy have a significantly higher risk of death than the general population. Sudden unexpected death in epilepsy (SUDEP) is the leading cause of sudden death among patients with epilepsy. Despite on-going research, there are still deficits in our knowledge about the mechanisms, genetic factors, and prevention of SUDEP. Current evidence suggests that cardiac arrhythmias, respiratory dysfunction, and brainstem arousal system dysfunction are the major mechanisms of SUDEP, and animal models support the role of neurotransmitters, especially serotonin and adenosine, in pathophysiology of SUDEP...
April 18, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29667443/implications-of-structural-and-functional-brain-changes-in-amyotrophic-lateral-sclerosis
#7
Thanuja Dharmadasa, William Huynh, Jun Tsugawa, Yoshimitsu Shimatani, Yan Ma, Matthew C Kiernan
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes progressive muscle weakness and disability, eventually leading to death. Heterogeneity of disease has become a major barrier to understanding key clinical questions such as prognosis and disease spread, and has disadvantaged clinical trials in search of therapeutic intervention. Patterns of disease have been explored through recent advances in neuroimaging, elucidating structural, molecular and functional changes. Unique brain signatures have emerged that have lent a greater understanding of critical disease mechanisms, offering opportunities to improve diagnosis, guide prognosis, and establish candidate biomarkers to direct future therapeutic strategies...
April 19, 2018: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/29667320/flotillin-1-interacts-with-the-serotonin-transporter-and-modulates-chronic-corticosterone-response
#8
Sonali N Reisinger, Eryan Kong, Barbara Molz, Thomas Humberg, Spyros Sideromenos, Ana Cicvaric, Thomas Steinkellner, Jae-Won Yang, Maureen Cabatic, Francisco J Monje, Harald H Sitte, Benjamin J Nichols, Daniela D Pollak
Aberrant serotonergic neurotransmission in the brain is considered at the core of the pathophysiological mechanisms involved in neuropsychiatric disorders. Gene by environment interactions contribute to the development of depression and involve modulation of the availability and functional activity of the serotonin transporter (SERT). Using behavioral and in vivo electrophysiological approaches together with biochemical, molecular-biological and molecular imaging tools we establish Flotillin-1 (Flot1) as a novel protein interacting with SERT and demonstrate its involvement in the response to chronic corticosterone (CORT) treatment...
April 18, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29667298/distinct-chromatin-structures-at-the-monoamine-oxidase-a-maoa-promoter-correlate-with-allele-specific-expression-in-sh-sy5y-cells
#9
M Manca, V Pessoa, P Myers, A Pickles, J Hill, H Sharp, C Murgatroyd, V J Bubb, J P Quinn
Monoamine oxidase-A (MAOA) metabolises monoamines and is implicated in the pathophysiology of psychiatric disorders. A polymorphic repetitive DNA domain, termed the uVNTR (upstream variable number tandem repeat), located at the promoter of the MAOA gene is a risk factor for many of these disorders. MAOA is on the X chromosome suggesting gender could play a role in regulation. We analysed MAOA regulation in the human female cell line, SH-SY5Y, which is polymorphic for the uVNTR. This heterozygosity allowed us to correlate allele specific gene expression with allele specific transcription factor binding and epigenetic marks for MAOA...
April 18, 2018: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29667232/the-pleiotropic-cardiovascular-effects-of-dipeptidyl-peptidase-4-inhibitors
#10
REVIEW
Angelo Avogaro, Gian Paolo Fadini
Patients with Type 2 Diabetes have an excess risk for cardiovascular disease. One of the several approaches, included in the Guidelines for the management of Type 2 Diabetes, is based on dipeptidyl peptidase 4 (DPP-4; also termed CD26) inhibitors (DPP-4-I), also called gliptins. Gliptins inhibit the degradation of glucagon-like peptide-1 GLP-1RA: this effect is associated with increased circulating insulin-to-glucagon ratio, and a consequent reduction of HbA1c. Beside incretin hormones, there are several proteins that may be affected by DPP-4 and its inhibition: among these some are relevant for the cardiovascular system homeostasis such as SDF-1α and its receptor CXCR4, brain natriuretic peptides, neuropeptide Y, and peptide YY...
April 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29667180/pde5-inhibitors-pharmacology-and-clinical-applications-20-years-after-sildenafil-discovery
#11
REVIEW
K-E Andersson
The discovery of the nitric oxide/cyclic cGMP pathway was the basis for our understanding of many normal physiological functions and the pathophysiology of several diseases. Since the discovery and introduction of sildenafil, inhibitors of phosphodiesterase isoenzymes type 5 (PDE5) have been first-line therapy for erectile dysfunction (ED). The success of sildenafil in the treatment of ED stimulated research in the field of PDE5 inhibition and led to many new applications, such as treatment of lower urinary symptoms (LUTS), and pulmonary arterial hypertension, which are now approved indications...
April 17, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29667027/neonatal-overfeeding-impairs-differentiation-potential-of-mice-subcutaneous-adipose-mesenchymal-stem-cells
#12
Isabelle Dias, Ísis Salviano, André Mencalha, Simone Nunes de Carvalho, Alessandra Alves Thole, Laís Carvalho, Erika Cortez, Ana Carolina Stumbo
Nutritional changes in the development (intrauterine life and postnatal period) may trigger long-term pathophysiological complications such as obesity and cardiovascular disease. Metabolic programming leads to organs and tissues modifications, including adipose tissue, with increased lipogenesis, production of inflammatory cytokines, and decreased glucose uptake. However, stem cells participation in adipose tissue dysfunctions triggered by overfeeding during lactation has not been elucidated. Therefore, this study was the first to evaluate the effect of metabolic programming on adipose mesenchymal stem cells (ASC) from mice submitted to overfeeding during lactation, using the litter reduction model...
April 17, 2018: Stem Cell Reviews
https://www.readbyqxmd.com/read/29667012/bone-marrow-adipocyte-developmental-origin-and-biology
#13
REVIEW
Joanna Bukowska, Trivia Frazier, Stanley Smith, Theodore Brown, Robert Bender, Michelle McCarthy, Xiying Wu, Bruce A Bunnell, Jeffrey M Gimble
PURPOSE OF REVIEW: This review explores how the relationships between bone marrow adipose tissue (BMAT) adipogenesis with advancing age, obesity, and/or bone diseases (osteopenia or osteoporosis) contribute to mechanisms underlying musculoskeletal pathophysiology. RECENT FINDINGS: Recent studies have re-defined adipose tissue as a dynamic, vital organ with functions extending beyond its historic identity restricted solely to that of an energy reservoir or sink. "State of the art" methodologies provide novel insights into the developmental origin, physiology, and function of different adipose tissue depots...
April 18, 2018: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/29666995/disturbed-left-and-right-ventricular-kinetic-energy-in-patients-with-repaired-tetralogy-of-fallot-pathophysiological-insights-using-4d-flow-mri
#14
Pia Sjöberg, Sebastian Bidhult, Jelena Bock, Einar Heiberg, Håkan Arheden, Ronny Gustafsson, Shahab Nozohoor, Marcus Carlsson
OBJECTIVES: Indications for pulmonary valve replacement (PVR) in patients with pulmonary regurgitation (PR) after repaired tetralogy of Fallot (rToF) are debated. We aimed to compare right (RV) and left ventricular (LV) kinetic energy (KE) measured by 4D-flow magnetic resonance imaging (MRI) in patients to controls, to further understand the pathophysiological effects of PR. METHODS: Fifteen patients with rToF with PR > 20% and 14 controls underwent MRI. Ventricular volumes and KE were quantified from cine MRI and 4D-flow, respectively...
April 17, 2018: European Radiology
https://www.readbyqxmd.com/read/29666932/-complex-regional-pain-syndrome-crps-an-update
#15
V Dimova, F Birklein
The acute phase of complex regional pain syndrome (CRPS) is pathophysiologically characterized by an activation of the immune system and its associated inflammatory response. During the course of CRPS, central nervous symptoms like mechanical hyperalgesia, loss of sensation, and body perception disorders develop. Psychological factors such as pain-related anxiety and traumatic events might have a negative effect on the treatment outcome. While the visible inflammatory symptoms improve, the pain often persists...
April 17, 2018: Der Schmerz
https://www.readbyqxmd.com/read/29666931/genome-editing-and-induced-pluripotent-stem-cell-technologies-for-personalized-study-of-cardiovascular-diseases
#16
REVIEW
Young Wook Chun, Matthew D Durbin, Charles C Hong
PURPOSE OF REVIEW: The goal of this review is to highlight the potential of induced pluripotent stem cell (iPSC)-based modeling as a tool for studying human cardiovascular diseases. We present some of the current cardiovascular disease models utilizing genome editing and patient-derived iPSCs. RECENT FINDINGS: The incorporation of genome-editing and iPSC technologies provides an innovative research platform, providing novel insight into human cardiovascular disease at molecular, cellular, and functional level...
April 17, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29666881/pathological-factors-contributing-to-crossed-cerebellar-diaschisis-in-cerebral-gliomas-a-study-combining-perfusion-diffusion-and-structural-mr-imaging
#17
Xiaoxue Liu, Jianrui Li, Qiang Xu, Dante Mantini, Peng Wang, Yuan Xie, Yifei Weng, Chiyuan Ma, Kangjian Sun, Zhiqiang Zhang, Guangming Lu
PURPOSE: To investigate imaging features of crossed cerebellar diaschisis (CCD) in cerebral gliomas, and its underlying pathophysiological mechanisms. METHODS: Thirty-three pre-surgical patients with cerebral gliomas and 33 healthy controls underwent arterial spin-labeling, diffusion tensor imaging, and high-resolution T1-weighted imaging using MRI, in order to estimate cerebral blood flow (CBF), white matter integrity, and lesion volume, respectively. Asymmetry indices of CBF in the cerebellum were used for evaluating the level of CCD in the patients...
April 17, 2018: Neuroradiology
https://www.readbyqxmd.com/read/29666878/-methemoglobinemia-after-inhalation-of-poppers
#18
U Janssens, S Hillen, T Janssens, J Grafe
BACKGROUND: This case report presents a case of symptomatic methemoglobinemia (MetHb 31.6%) after inhalation of volatile nitrites (poppers). METHODS: The patient's medical history and symptoms are discussed together with pathophysiology of methemoglobinemia, diagnostics, and antidote therapy. Pulse oxymetry, arterial blood gas analysis, and CO-oximetry receive particular attention as well as antidote therapy with methylene blue. RESULTS: The patient was treated successfully with intravenous methylene blue...
April 17, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/29666786/modeling-neuropsychiatric-and-neurodegenerative-diseases-with-induced-pluripotent-stem-cells
#19
REVIEW
Elizabeth A LaMarca, Samuel K Powell, Schahram Akbarian, Kristen J Brennand
Human-induced pluripotent stem cells (hiPSCs) have revolutionized our ability to model neuropsychiatric and neurodegenerative diseases, and recent progress in the field is paving the way for improved therapeutics. In this review, we discuss major advances in generating hiPSC-derived neural cells and cutting-edge techniques that are transforming hiPSC technology, such as three-dimensional "mini-brains" and clustered, regularly interspersed short palindromic repeats (CRISPR)-Cas systems. We examine specific examples of how hiPSC-derived neural cells are being used to uncover the pathophysiology of schizophrenia and Parkinson's disease, and consider the future of this groundbreaking research...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29666415/canonical-pi3k%C3%AE-signaling-in-myeloid-cells-restricts-trypanosoma-cruzi-infection-and-dampens-chagasic-myocarditis
#20
Maria C Silva, Marcela Davoli-Ferreira, Tiago S Medina, Renata Sesti-Costa, Grace K Silva, Carla D Lopes, Lucas E Cardozo, Fábio N Gava, Konstantina Lyroni, Fabrício C Dias, Amanda F Frade, Monique Baron, Helder I Nakaya, Florêncio Figueiredo, José C Alves-Filho, Fernando Q Cunha, Christos Tsatsanis, Christophe Chevillard, Edecio Cunha-Neto, Emilio Hirsch, João S Silva, Thiago M Cunha
Chagas disease is caused by infection with the protozoan Trypanosoma cruzi (T. cruzi) and is an important cause of severe inflammatory heart disease. However, the mechanisms driving Chagas disease cardiomyopathy have not been completely elucidated. Here, we show that the canonical PI3Kγ pathway is upregulated in both human chagasic hearts and hearts of acutely infected mice. PI3Kγ-deficient mice and mutant mice carrying catalytically inactive PI3Kγ are more susceptible to T. cruzi infection. The canonical PI3Kγ signaling in myeloid cells is essential to restrict T...
April 17, 2018: Nature Communications
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