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Molecular pathology

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https://www.readbyqxmd.com/read/28927263/molecular-and-cellular-basis-of-neurodegeneration-in-alzheimer-s-disease
#1
Sangyun Jeong
The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid beta-peptide (Abeta) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than Abeta plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD...
September 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28927250/gut-microbiota-and-the-liver
#2
Alessandro Federico, Marcello Dallio, Giuseppe G Caprio, Vittorio M Ormando, Carmela Loguercio
Nowadays liver diseases represent one of major healthy problems in the world in terms of morbidity and mortality. The high prevalence of liver pathologies represents the key point to understand the necessity to identify the pathogenetic mechanisms that support these disorders in order to nurse them. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Gut microbiota is considered both as a promoting factor and as a potential therapeutic target of a large number of liver pathologies due to the connection between intestine and liver: the gut-liver axis...
December 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28927226/female-clock%C3%AE-19-%C3%AE-19-mice-are-protected-from-the-development-of-age-dependent-cardiomyopathy
#3
Faisal J Alibhai, Cristine J Reitz, Willem T Peppler, Poulami Basu, Paul Sheppard, Elena Choleris, Marica Bakovic, Tami A Martino
Aims: Circadian rhythms are important for healthy cardiovascular physiology and they are regulated by the molecular circadian mechanism. Previously, we showed that disruption of the circadian mechanism factor CLOCK in male Clock Δ19/Δ19 mice led to development of age-dependent cardiomyopathy. Here, we investigate the role of biological sex in protecting against heart disease in aging female Clock Δ19/Δ19 mice. Methods and results: Female Clock Δ19/Δ19 mice are protected from the development of cardiomyopathy with age, as heart structure and function are similar to 18 months of age versus female WT mice...
September 12, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28926971/mini-review-the-contribution-of-intermediate-phenotypes-to-gxe-effects-on-disorders-of-body-composition-in-the-new-omics-era
#4
REVIEW
Edna J Nava-Gonzalez, Esther C Gallegos-Cabriales, Irene Leal-Berumen, Raul A Bastarrachea
Studies of gene-environment (GxE) interactions describe how genetic and environmental factors influence the risk of developing disease. Intermediate (molecular or clinical) phenotypes (IPs) are traits or metabolic biomarkers that mediate the effects of gene-environment influences on risk behaviors. Functional systems genomics discovery offers mechanistic insights into how DNA variations affect IPs in order to detect genetic causality for a given disease. Disorders of body composition include obesity (OB), Type 2 diabetes (T2D), and osteoporosis (OSTP)...
September 17, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28926890/-progress-of-molecular-subtypes-of-colorectal-cancer
#5
Z Y Chen, X Wang, T Wu, Y C Liu, P Y Wang
Colorectal cancer is one of the leading causes of morbidity and mortality around the world. Although the staging and classification systems, such as tumor/node/metastasis (TNM) staging, are widely used in clinic, there are some limitations. For example, the patients with the same pathological type, TNM stage and treatment regimen show a completely different prognosis and outcome. In the present, molecular subtyping was concerned for a more precise and accurate staging of colorectal cancer. Herein, we reviewed the literature of the molecular subtypes of colorectal cancer in the past decades...
September 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28926867/diabetes-associated-biobanking-more-topical-than-ever
#6
Katharina Lydia Kynast, Nadine Volk, Thomas Fleming, Esther Herpel
The increasing prevalence of diabetes and its accompanying long-term complications, as well as the associated economic burden, calls for a rapid clinical translation of biomedical research to better valid the physiological relevance of the findings from basic research. To meet this condition, the Collaborative Research Center (CRC) 1118 has established the first nationwide diabetes-specific Biomaterialbank (BMB) that permanently preserves solid and liquid specimen retro- and prospectively at the Institute of Pathology and Department of Endocrinology of the University Hospital Heidelberg...
September 19, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28926831/multiparameter-investigation-of-a-46-xx-46-xy-tetragametic-chimeric-phenotypical-male-patient-with-bilateral-scrotal-ovotestes-and-ovulatory-activity
#7
Yolande van Bever, Katja P Wolffenbuttel, Hennie T Brüggenwirth, Eric Blom, Annelies de Klein, Bert H J Eussen, Florijn van der Windt, Sabine E Hannema, Arianne B Dessens, Lambert C J Dorssers, Katharina Biermann, Remko Hersmus, Yolanda B de Rijke, Leendert H J Looijenga
We report on an adult male initially presenting with gynecomastia and a painless scrotal mass without additional genital anomalies. Hyperpigmentation of the skin following the Blaschko's lines was identified. He underwent gonadectomy because of suspected cancer. Histological analyses revealed an ovotestis with ovulatory activity confirmed by immunohistochemistry with multiple markers. Karyotyping of cultured peripheral blood lymphocytes and a buccal smear revealed a 46,XX/46,XY chimeric constitution with different percentages...
September 20, 2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28926803/distribution-of-chromosome-breakpoints-in-benzene-exposed-and-unexposed-aml-patients
#8
Patrick J Kerzic, Richard D Irons
Results of laboratory studies and investigations of occupationally exposed healthy individuals have been used to develop a mode of action for benzene-induced leukemia that mirrors disease following treatment with chemotherapeutic agents. Recently we have described series of AML and MDS cases with benzene exposure history, and have provided cytogenetic, molecular, and pathologic evidence that these cases differ significantly in many features from therapy-related disease. Here we have extended this work, and describe chromosome breakpoints across 441 identifiable regions, in terms of gains or losses, in 710 AML cases collected during the Shanghai Health Study, which include 75 with a history of benzene exposure...
September 1, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28926706/structural-and-kinetic-characterization-of-the-intrinsically-disordered-protein-sev-ntail-through-enhanced-sampling-simulations
#9
Mattia Bernetti, Matteo Masetti, Fabio Pietrucci, Martin Blackledge, Malene Ringkjøbing Jensen, Maurizio Recanatini, Luca Mollica, Andrea Cavalli
Intrinsically disordered proteins (IDPs) are emerging as an important class of the proteome. Being able to interact with different molecular targets, they participate in many physiological and pathological activities. However, due to their intrinsically heterogeneous nature, determining the equilibrium properties of IDPs is still a challenge for biophysics. Herein, we applied state-of-the-art enhanced sampling methods to Sev NTAIL, a test case of IDPs, and constructed a bin-based kinetic model to unveil the underlying kinetics...
September 19, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28926471/role-of-fat-soluble-vitamins-in-osteoarthritis-management
#10
Xiao-Yan Zheng, Jun Liang, Yu-Sheng Li, Min Tu
Osteoarthritis (OA) is a chronic degenerative joint disease, in which metabolic imbalance in bone is observed. The pathological mechanism of metabolic imbalance is not clear yet, but the nutritional factors, particularly the vitamins, might be intrinsic to the development and progression of OA. In this review article, we have explored databases such as PubMed, Scopus, and Google Scholar articles until the beginning of 2017 and reviewed the role of fat-soluble vitamins in pathological and therapeutic aspects of OA...
September 19, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28926133/synthesis-of-thiophene-based-optical-ligands-that-selectively-detect-tau-pathology-in-alzheimer%C3%A2-s-disease
#11
Peter Nilsson, Hamid Shirani, Hanna Appelqvist, Marcus Bäck, Therese Klingstedt, Nigel Cairns
The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the development of molecular ligands able to detect these pathological hallmarks is essential. Here, we report the synthesis of thiophene based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs) that can be utilized for selective assignment of tau aggregates in brain tissue with Alzheimer´s disease (AD) pathology. The ability of the ligands to selectively distinguish tau deposits from the other AD associated pathological hallmark, senile plaques consisting of aggregated amyloid-β (Aβ) peptide, were reduced when the chemical composition of the ligands were altered, verifying that specific molecular interactions between the ligands and the aggregates are necessary for the selective detection of tau deposits...
September 19, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28926093/pulmonary-hypertension-molecular-aspects-of-current-therapeutic-intervention-and-future-direction
#12
Taruna Katyal Arora, Amit KumarArora, Monika Katyal Sachdeva, Satyendra Kumar Rajput, Arun Kumar Sharma
Pulmonary hypertension (PH) is a life-threatening lung disorder with towering prevalence and risk for future has been gradually rising worldwide. Even, no specific medications are available for pulmonary hypertension; various classes of treatment based upon the origin and magnitude of hypertension are still used for the treatment of PH. Consideration of molecular or signaling modulation is the imperative approach that can offer a new notion for prevalent pharmacotherapeutic agents. Instead of concurrent targets, including endothelin receptor antagonists (ETA/ETB), phosphodiesterase 5 inhibitor (PDF-5), calcium channel blockers, anticoagulants, diuretics and long acting prostacyclin analogue, recent scientific reports revealed the numerous potential alternative therapeutic approaches that can significantly target the pathological signaling alteration associated with PH...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925390/alterations-of-micrornas-throughout-the-malignant-evolution-of-cutaneous-squamous-cell-carcinoma-the-role-of-mir-497-in-epithelial-to-mesenchymal-transition-of-keratinocytes
#13
A Mizrahi, A Barzilai, D Gur-Wahnon, I Z Ben-Dov, S Glassberg, T Meningher, E Elharar, M Masalha, J Jacob-Hirsch, H Tabibian-Keissar, I Barshack, J Roszik, R Leibowitz-Amit, Y Sidi, D Avni
Skin carcinogenesis is known to be a multi-step process with several stages along its malignant evolution. We hypothesized that transformation of normal epidermis to cutaneous squamous cell carcinoma (cSCC) is causally linked to alterations in microRNAs (miRNA) expression. For this end we decided to evaluate their alterations in the pathologic states ending in cSCC. Total RNA was extracted from formalin fixed paraffin embedded biopsies of five stages along the malignant evolution of keratinocytes towards cSCC: Normal epidermis, solar elastosis, actinic keratosis KIN1-2, advanced actinic keratosis KIN3 and well-differentiated cSCC...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28925274/-a-case-report-of-peritoneal-tuberculosis-the-diagnostic-role-of-pet-ct-and-laparoscopy
#14
H Macháčková, R Pilka, S Losse, M Žurková, V Lošťáková, T Tichý, Y Lovečková
OBJECTIVE: We present a case of peritoneal tuberculosis of young woman with focus on difficult diagnosis of this low incidence disease in developed countries. DESIGN: Case report. SETTING: Department of Gynaecology and Obstetrics, Faculty Hospital, Olomouc. Department of Obstetric and Gynaecology, Nový Jičín Hospital. Department of Pulmonary Diseases and Tuberculosis, Faculty Hospital, Olomouc. Department of Pathology nad Molecular Medicine, Faculty Hospital, Olomouc...
2017: Ceská Gynekologie
https://www.readbyqxmd.com/read/28925253/novel-trimodal-maldi-imaging-mass-spectrometry-ims3-at-10-%C3%AE-m-reveals-spatial-lipid-and-peptide-correlates-implicated-in-a%C3%AE-plaque-pathology-in-alzheimer-s-disease
#15
Ibrahim Kaya, Dimitri Brinet, Wojciech Michno, Mehmet Baskurt, Henrik Zetterberg, Kaj Blennow, Jörg Hanrieder
Multimodal chemical imaging using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) can provide comprehensive molecular information in situ within the same tissue sections. This is of relevance for studying different brain pathologies such as Alzheimer's Disease (AD), where recent data suggest a critical relevance of co-localizing Aβ peptides and neuronal lipids. We here developed a novel trimodal, high-resolution (10µm) MALDI imaging MS (IMS) paradigm for negative- and positive ion mode lipid analysis and subsequent protein ion imaging on the same tissue section...
September 19, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28924976/spontaneous-generation-of-a-novel-foetal-human-retinal-pigment-epithelium-rpe-cell-line-available-for-investigation-on-phagocytosis-and-morphogenesis
#16
Zhihua Shao, Haiyun Wang, Xuejian Zhou, Baosen Guo, Xuehu Gao, Zengrong Xiao, Meng Liu, Jihong Sha, Chunlian Jiang, Yuping Luo, Zhixue Liu, Siguang Li
OBJECTIVES: Primary retinal pigment epithelium (RPE) cells have a limited capacity to re-establish epithelial morphology and to maintain native RPE function in vitro, and all commercially available RPE cell lines have drawbacks of morphology or function; therefore, the establishment of new RPE cell lines with typical characteristics of RPE would be helpful in further understanding of their physiological and pathological mechanisms. Here, we firstly report a new spontaneously generated RPE line, fhRPE-13A, from a 13-week aborted foetus...
September 18, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28924365/effects-of-hypobaric-hypoxia-on-rat-retina-and-protective-response-of-resveratrol-to-the-stress
#17
Xiaorong Xin, Hong Dang, Xiaojing Zhao, Haohao Wang
High-altitude retinopathy represents retinal functional changes associated with environmental challenges imposed by hypobaric hypoxia, but the detailed cellular and molecular mechanism underlying this process remains unclear. Our current investigation was to explore the effect of hypobaric hypoxia on the rat retina and determine whether resveratrol has a protective efficacy on the hypoxic damage to the retina. Experiment rats were randomly grouped as the control group, hypoxia group and resveratrol intervention group...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28923922/trkb-neurotrophic-activities-are-blocked-by-%C3%AE-synuclein-triggering-dopaminergic-cell-death-in-parkinson-s-disease
#18
Seong Su Kang, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Matthew J Benskey, Xuebing Cao, Jun Xu, Yi E Sun, Keqiang Ye
BDNF/TrkB neurotrophic signaling is essential for dopaminergic neuronal survival, and the activities are reduced in the substantial nigra (SN) of Parkinson's disease (PD). However, whether α-Syn (alpha-synuclein) aggregation, a hallmark in the remaining SN neurons in PD, accounts for the neurotrophic inhibition remains elusive. Here we show that α-Syn selectively interacts with TrkB receptors and inhibits BDNF/TrkB signaling, leading to dopaminergic neuronal death. α-Syn binds to the kinase domain on TrkB, which is negatively regulated by BDNF or Fyn tyrosine kinase...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923905/acute-coronary-syndromes-the-way-forward-from-mechanisms-to-precision-treatment
#19
REVIEW
Filippo Crea, Peter Libby
Well into the 21st century, we still triage acute myocardial infarction on the basis of the presence or absence of ST-segment elevation, a century-old technology. Meanwhile, we have learned a great deal about the pathophysiology and mechanisms of acute coronary syndromes (ACS) at the clinical, pathological, cellular, and molecular levels. Contemporary imaging studies have shed new light on the mechanisms of ACS. This review discusses these advances and their implications for clinical management of the ACS for the future...
September 19, 2017: Circulation
https://www.readbyqxmd.com/read/28923828/attenuated-pdgf-signaling-drives-alveolar-and-microvascular-defects-in-neonatal-chronic-lung%C3%A2-disease
#20
Prajakta Oak, Tina Pritzke, Isabella Thiel, Markus Koschlig, Daphne S Mous, Anita Windhorst, Noopur Jain, Oliver Eickelberg, Kai Foerster, Andreas Schulze, Wolfgang Goepel, Tobias Reicherzer, Harald Ehrhardt, Robbert J Rottier, Peter Ahnert, Ludwig Gortner, Tushar J Desai, Anne Hilgendorff
Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O2). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O2 In the context of MV-O2, attenuated PDGF signaling independently contributes to defective septation and endothelial cell apoptosis stemming from a PDGF-Rα-dependent reduction in lung VEGF-A...
September 18, 2017: EMBO Molecular Medicine
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