2,316 results match your criteria pathways dysfunctional

Patterns of Child Maltreatment and the Development of Conflictual Emerging Adult Romantic Relationships: An Examination of Mechanisms and Gender Moderation.

Child Maltreat 2021 Jun 8:10775595211022837. Epub 2021 Jun 8.

Mt. Hope Family Center, 6927University of Rochester, NY, USA.

Individuals who experienced child maltreatment are at heightened risk for involvement in conflictual romantic relationships. The aim of this study was to examine the effect of patterns of child maltreatment on the development of maladaptive romantic relationships in emerging adulthood (EA), as well as to determine whether childhood physical aggression and disinhibition mediate this risk. Utilizing a longitudinal sample of emerging adult participants ( = 398 emerging adults; M = 19. Read More

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Pathophysiology of Coagulopathy in Hematological Malignancies and in COVID-19.

Marcel Levi

Hemasphere 2021 Jun 1;5(6):e571. Epub 2021 Jun 1.

Department of Medicine and Cardiometabolic Programme-NIHR UCLH/UCL BRC, University College London Hospitals NHS Foundation Trust, London, United Kingdom.

Many severe illnesses with a systemic impact may cause activation of coagulation. While systemic activation of coagulation leads to a coagulopathy that follows many common activation pathways and failure of endogenous regulatory anticoagulant systems, underlying conditions may utilize distinctive pathogenetic routes and may vary in clinical manifestations of the coagulopathy. The coagulation derangement associated with hematological malignancies and the coagulopathy of coronavirus disease 2019 (COVID-19) clearly demonstrate such differences. Read More

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Cancer cell-selective modulation of mitochondrial respiration and metabolism by potent organogold(iii) dithiocarbamates.

Chem Sci 2020 Sep 18;11(38):10465-10482. Epub 2020 Sep 18.

Department of Chemistry, University of Kentucky Lexington KY 40506 USA

Metabolic reprogramming is a key cancer hallmark that has led to the therapeutic targeting of glycolysis. However, agents that target dysfunctional mitochondrial respiration for targeted therapy remains underexplored. We report the synthesis and characterization of ten (10) novel, highly potent organometallic gold(iii) complexes supported by dithiocarbamate ligands as selective inhibitors of mitochondrial respiration. Read More

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September 2020

Altered A-type potassium channel function impairs dendritic spike initiation and temporoammonic long-term potentiation in Fragile X syndrome.

J Neurosci 2021 Jun 1. Epub 2021 Jun 1.

Department of Neuroscience, Institute for Neuroscience, Center for Learning and Memory, University of Texas at Austin, 78712

Fragile X syndrome (FXS) is the leading monogenetic cause of cognitive impairment and autism spectrum disorder. Area CA1 of the hippocampus receives current information about the external world from the entorhinal cortex via the temporoammonic (TA) pathway. Given its role in learning and memory, it is surprising that little is known about TA long-term potentiation (TA-LTP) in FXS. Read More

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Metabolomic Biomarkers in Gestational Diabetes Mellitus: A Review of the Evidence.

Int J Mol Sci 2021 May 24;22(11). Epub 2021 May 24.

Monash Centre for Health Research and Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, Melbourne 3168, Australia.

Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes, affecting between 2 to 38% of pregnancies worldwide, varying considerably depending on diagnostic criteria used and sample population studied. Adverse obstetric outcomes include an increased risk of macrosomia, and higher rates of stillbirth, instrumental delivery, and birth trauma. Metabolomics, which is a platform used to analyse and characterise a large number of metabolites, is increasingly used to explore the pathophysiology of cardiometabolic conditions such as GDM. Read More

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Mitophagy and Oxidative Stress: The Role of Aging.

Antioxidants (Basel) 2021 May 17;10(5). Epub 2021 May 17.

Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early responses to excessive reactive oxygen species (ROS) production is the induction of mitophagy to remove damaged mitochondria. Read More

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CLN5 and CLN3 function as a complex to regulate endolysosome function.

Biochem J 2021 Jun 1. Epub 2021 Jun 1.

INRS-Institut Armand-Frappier, Laval, Canada.

CLN5 is a soluble endolysosomal protein whose function is poorly understood. Mutations in this protein cause a rare neurodegenerative disease, Neuronal Ceroid Lipofuscinosis. We previously found that depletion of CLN5 leads to dysfunctional retromer, resulting in the degradation of the lysosomal sorting receptor, sortilin. Read More

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Model-based analysis uncovers mutations altering autophagy selectivity in human cancer.

Nat Commun 2021 05 31;12(1):3258. Epub 2021 May 31.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, China.

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. Read More

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Diesel exhaust exposure alters the expression of networks implicated in neurodegeneration in zebrafish brains.

Cell Biol Toxicol 2021 May 31. Epub 2021 May 31.

Department of Neurology, David Geffen School of Medicine At UCLA, 710 Westwood Plaza, Los Angeles, CA, 90095, USA.

Neurodegenerative diseases are a major cause of disability in the world, but their etiologies largely remain elusive. Genetic factors can only account for a minority of risk for most of these disorders, suggesting environmental factors play a significant role in the development of these diseases. Prolonged exposure to air pollution has recently been identified to increase the risk of Alzheimer's and Parkinson's diseases, but the molecular mechanisms by which it acts are not well understood. Read More

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Oxidative Modifications of RNA and Its Potential Roles in Biosystem.

Front Mol Biosci 2021 12;8:685331. Epub 2021 May 12.

Biochemistry and Biophysics Center, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States.

Elevated level of oxidized RNA was detected in vulnerable neurons in Alzheimer patients. Subsequently, several diseases and pathological conditions were reported to be associated with RNA oxidation. In addition to several oxidized derivatives, cross-linking and unique strand breaks are generated by RNA oxidation. Read More

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[Stress and pathophysiological mechanisms for the development of psychosomatic disease].

Psychiatriki 2021 May 28. Epub 2021 May 28.

Hellenic Psychiatric Association.

According to the biopsychosocial model, disease is the dysfunctional resultant of various fields of human function (biological, psychological, behavioral, socioeconomic). This article deals with the psycho-biological field of Psychosomatic research, namely, the effect of stress on the body. The human organism, in the prospect of evolution, has developed biological mechanisms for maintaining its homeostasis (ομοιόσταση), in its interchange with the stressor stimuli. Read More

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Loss of Setd2 associates with aberrant microRNA expression and contributes to inflammatory bowel disease progression in mice.

Genomics 2021 May 28;113(4):2441-2454. Epub 2021 May 28.

Shanghai Mental Health Center, School of Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, China. Electronic address:

Both SETD2-mediated H3K36me3 and miRNAs play critical epigenetic roles in inflammatory bowel disease (IBD) and involve in the dysfunctional intestinal barrier. However, little is known about cross-talk between these two types of regulators in IBD progression. We performed small RNA sequencing of Setd2 epithelium-specific knockout mice (Setd2) and wild-type controls, both with DSS-induced colitis, and designed a framework for integrative analysis. Read More

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MMP2 and TLRs modulate immune responses in the tumor microenvironment.

JCI Insight 2021 May 25. Epub 2021 May 25.

The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, United States of America.

The presence of an immunosuppressive tumor microenvironment is a major obstacle in the success of cancer immunotherapies. Because extracellular matrix components can shape the microenvironment, we investigated the role of matrix metalloproteinase 2 (MMP2) in melanoma tumorigenesis. Significantly, we found that MMP2 signals pro-inflammatory pathways on antigen presenting cells which requires both toll-like receptor (TLR) 2 and TLR4. Read More

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MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function.

J Immunol 2021 Jun 21;206(11):2725-2739. Epub 2021 May 21.

School of Immunology and Microbial Sciences, King's College London, London, United Kingdom;

Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor-biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. Read More

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The Dopamine Hypothesis of Autism Spectrum Disorder Revisited: Current Status and Future Prospects.

Dev Neurosci 2021 May 19:1-11. Epub 2021 May 19.

Department of Psychiatry, "Iuliu Hațieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. Read More

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Unearthing the Janus-face cholesterogenesis pathways in cancer.

Biochem Pharmacol 2021 May 16:114611. Epub 2021 May 16.

Department of Biology, Geology, and Physical Sciences, Sul Ross State University, Alpine, TX, USA. Electronic address:

Cholesterol biosynthesis, primarily associated with eukaryotes, occurs as an essential component of human metabolism with biosynthetic deregulation a factor in cancer viability. The segment that partitions between squalene and the C-end cholesterol yields the main cholesterogenesis branch subdivided into the Bloch and Kandutsch-Russell pathways. Their importance in cell viability, in normal growth and development originates primarily from the amphipathic property and shape of the cholesterol molecule which makes it suitable as a membrane insert. Read More

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Ataxin-2 gene: a powerful modulator of neurological disorders.

Curr Opin Neurol 2021 May 25. Epub 2021 May 25.

Department of Clinical Neuroscience (CNS), J5:20 Bioclinicum, Karolinska University Hospital, Stockholm, Sweden.

Purpose Of Review: To provide an update on the role of Ataxin-2 gene (ATXN2) in health and neurological diseases.

Recent Findings: There is a growing complexity emerging on the role of ATXN2 and its variants in association with SCA2 and several other neurological diseases. Polymorphisms and intermediate cytosine adenine guanine alleles in ATXN2 establish this gene as a powerful modulator of neurological diseases including lethal neurodegenerative conditions such as motor neuron disease, spinocerebellar ataxia 3 (SCA3), and peripheral nerve disease such as familial amyloidosis polyneuropathy. Read More

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Modulation of Cellular Fate of Vinyl Triarylamines through Structural Fine Tuning: To Stay or Not To Stay in the Mitochondria?

Chembiochem 2021 May 19. Epub 2021 May 19.

Institut Curie, Université PSL, CNRS UMR9187, Inserm U1196, Chemistry and Modelling for the Biology of Cancer, 91400, Orsay, France.

Mitochondria are involved in many cellular pathways and dysfunctional mitochondria are linked to various diseases. Hence efforts have been made to design mitochondria-targeted fluorophores for monitoring the mitochondrial status. However, the factors that govern the mitochondria-targeted potential of dyes are not well-understood. Read More

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Emerging Roles of Impaired Autophagy in Fatty Liver Disease and Hepatocellular Carcinoma.

Int J Hepatol 2021 22;2021:6675762. Epub 2021 Apr 22.

Julius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University Durham, NC 27707, USA.

Autophagy is a conserved catabolic process that eliminates dysfunctional cytosolic biomolecules through vacuole-mediated sequestration and lysosomal degradation. Although the molecular mechanisms that regulate autophagy are not fully understood, recent work indicates that dysfunctional/impaired autophagic functions are associated with the development and progression of nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), and hepatocellular carcinoma (HCC). Autophagy prevents NAFLD and AFLD progression through enhanced lipid catabolism and decreasing hepatic steatosis, which is characterized by the accumulation of triglycerides and increased inflammation. Read More

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Etiology of Belief-behavior Systems and Hierarchies.

Mihal Emberton

Perm J 2021 May;25

None: Introduction: In order to understand the well documented patterns of mental health, human learning, human behavior, and the mechanics of hierarchies such as academic institutions, political systems, and business organizations, one must discover the rules and pathways that cause those patterns. My Belief-Behavior Systems archetype is the first of its kind to reconcile the theories and insights from social sciences, political science, psychiatry, and evolutionary biology into a unifying paradigm which explains how socialization and human interactions evolved into the patterns we recognized today. More importantly is that this new contribution to our understanding of human behavior within hierarchies provides the key insights to guide the restoration and repair of our dysfunctional hierarchies which, unfortunately, all too often oppress, manipulate and exploit our humanity. Read More

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Polycystic ovary syndrome: Pathways and mechanisms for possible increased susceptibility to COVID-19.

World J Clin Cases 2021 Apr;9(12):2711-2720

Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius LT-03101, Lithuania.

In 75% of women with polycystic ovary syndrome (PCOS), insulin action is impaired. In obesity, visceral adipose tissue becomes dysfunctional: Chronic inflammation is favored over storage, contributing to the development of metabolic complications. PCOS, metabolic syndrome (MetSy) and non-alcoholic fatty liver disease (NAFLD) apparently share common pathogenic factors; these include abdominal adiposity, excess body weight and insulin resistance. Read More

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The Warburg Effect: Historical Dogma Versus Current Rationale.

Adv Exp Med Biol 2021 ;1269:169-177

Center for Translational Cancer Research, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.

Contrary to Warburg's original thesis, accelerated aerobic glycolysis is not a primary and permanent consequence of dysfunctional mitochondria compensating for a poor ATP yield per mole glucose. Instead, the Warburg effect is an essential part of a "selfish" metabolic reprogramming, which results from the interplay between (normoxic or hypoxic) HIF-1 overexpression, oncogene activation (cMyc, Ras), loss of function of tumor suppressors (mutant p53, mutant PTEN, microRNAs and sirtuins with suppressor functions), activated (PI3K/Akt/mTORC1, Ras/Raf/Mek/Erk/c-Myc) or deactivated (AMPK) signaling pathways, components of the tumor microenvironment, and HIF-1 cooperations with epigenetic mechanisms. Molecular and functional processes of the Warburg effect include (a) considerably accelerated glycolytic fluxes; (b) adequate ATP generation per unit time to maintain energy homeostasis; (c) backup and diversion of glycolytic intermediates facilitating the biosynthesis of nucleotides, nonessential amino acids, lipids, and hexosamines; (d) inhibition of pyruvate entry into mitochondria; (e) excessive formation and accumulation of lactate which stimulates tumor growth and suppression of antitumor immunity (in addition, lactate can serve as an energy source for normoxic cancer cells, contributes to extracellular acidosis, and thus drives malignant progression and resistances to conventional therapies); (f) maintenance of the cellular redox homeostasis and low ROS formation; and (g) HIF-1 overexpression, mutant p53, and mutant PTEN which inhibit mitochondrial biogenesis and functions, thus negatively impacting cellular respiration rate. Read More

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A Panel of Five-lncRNA Signature as a Potential Biomarker for Predicting Survival in Gastric and Thoracic Cancers.

Front Genet 2021 13;12:666155. Epub 2021 Apr 13.

Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin, China.

Dysfunctional long non-coding RNAs (lncRNAs) have been found to have carcinogenic and/or tumor inhibitory effects in the development and progression of cancer, suggesting their potential as new independent biomarkers for cancer diagnosis and prognosis. The exploration of the relationship between lncRNAs and the overall survival (OS) of different cancers opens up new prospects for tumor diagnosis and treatment. In this study, we established a five-lncRNA signature and explored its prognostic efficiency in gastric cancer (GC) and several thoracic malignancies, including breast invasive carcinoma (BRCA), esophageal carcinoma, lung adenocarcinoma, lung squamous cell carcinoma (LUSC), and thymoma (THYM). Read More

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Control of T Cell Metabolism by Cytokines and Hormones.

Front Immunol 2021 13;12:653605. Epub 2021 Apr 13.

College of Medical and Dental Sciences, Institute of Immunology and Immunotherapy, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom.

Dynamic, coordinated changes in metabolic pathway activity underpin the protective and inflammatory activity of T cells, through provision of energy and biosynthetic precursors for effector functions, as well as direct effects of metabolic enzymes, intermediates and end-products on signaling pathways and transcriptional mechanisms. Consequently, it has become increasingly clear that the metabolic status of the tissue microenvironment directly influences T cell activity, with changes in nutrient and/or metabolite abundance leading to dysfunctional T cell metabolism and interlinked immune function. Emerging evidence now indicates that additional signals are integrated by T cells to determine their overall metabolic phenotype, including those arising from interaction with cytokines and hormones in their environment. Read More

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Common Principles and Specific Mechanisms of Mitophagy from Yeast to Humans.

Int J Mol Sci 2021 Apr 22;22(9). Epub 2021 Apr 22.

Institute of Biochemistry and Molecular Biology I, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.

Mitochondria are double membrane-bound organelles in eukaryotic cells essential to a variety of cellular functions including energy conversion and ATP production, iron-sulfur biogenesis, lipid and amino acid metabolism, and regulating apoptosis and stress responses. Mitochondrial dysfunction is mechanistically linked to several neurodegenerative diseases, cancer, and ageing. Excessive and dysfunctional/damaged mitochondria are degraded by selective autophagic pathways known as mitophagy. Read More

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Dysregulated Immunological Functionome and Dysfunctional Metabolic Pathway Recognized for the Pathogenesis of Borderline Ovarian Tumors by Integrative Polygenic Analytics.

Int J Mol Sci 2021 Apr 15;22(8). Epub 2021 Apr 15.

Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.

The pathogenesis and molecular mechanisms of ovarian low malignant potential (LMP) tumors or borderline ovarian tumors (BOTs) have not been fully elucidated to date. Surgery remains the cornerstone of treatment for this disease, and diagnosis is mainly made by histopathology to date. However, there is no integrated analysis investigating the tumorigenesis of BOTs with open experimental data. Read More

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Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness.

J Clin Med 2021 Apr 14;10(8). Epub 2021 Apr 14.

Department of Emergency Medicine, College of Medicine-Jacksonville, University of Florida, 655 West 8th Street, Jacksonville, FL 32209, USA.

In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by clearing bacterial toxins, supporting corticosteroid release, decreasing platelet aggregation, inhibiting endothelial cell apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of endothelial cell adhesion molecules. Read More

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Mitophagy in Human Diseases.

Int J Mol Sci 2021 Apr 9;22(8). Epub 2021 Apr 9.

Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain.

Mitophagy is a selective autophagic process, essential for cellular homeostasis, that eliminates dysfunctional mitochondria. Activated by inner membrane depolarization, it plays an important role during development and is fundamental in highly differentiated post-mitotic cells that are highly dependent on aerobic metabolism, such as neurons, muscle cells, and hepatocytes. Both defective and excessive mitophagy have been proposed to contribute to age-related neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, metabolic diseases, vascular complications of diabetes, myocardial injury, muscle dystrophy, and liver disease, among others. Read More

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Motor proteins at the mitochondria-cytoskeleton interface.

J Cell Sci 2021 Apr 13;134(7). Epub 2021 Apr 13.

Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Cambridge Biomedical Campus, The Keith Peters Building, Hills Road, Cambridge CB2 0XY, UK.

Mitochondria are multifunctional organelles that not only produce energy for the cell, but are also important for cell signalling, apoptosis and many biosynthetic pathways. In most cell types, they form highly dynamic networks that are constantly remodelled through fission and fusion events, repositioned by motor-dependent transport and degraded when they become dysfunctional. Motor proteins and their tracks are key regulators of mitochondrial homeostasis, and in this Review, we discuss the diverse functions of the three classes of motor proteins associated with mitochondria - the actin-based myosins, as well as the microtubule-based kinesins and dynein. Read More

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[Immune Microenvironment Comparation Study between EGFR Mutant and EGFR Wild Type Lung Adenocarcinoma Patients Based on TCGA Database].

Zhongguo Fei Ai Za Zhi 2021 Apr;24(4):236-244

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Background: Lung cancer is a malignant with high incidence and mortality and adenocarcinoma is among the most popular subtypes. Epidermal growth factor receptor (EGFR) mutation is one of the most important driver mutations for lung adenocarcinoma and EGFR-tyrosine kinase inhibitor (TKI) will benefit those patients with sensitive EGFR mutations. Recently, immune checkpoint inhibitor (ICI) therapy, provide a new breakthrough treatment for lung cancer patients. Read More

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