27,041 results match your criteria resistance impaired

Repression of the AURKA-CXCL5 axis induces autophagic cell death and promotes radiosensitivity in non-small-cell lung cancer.

Cancer Lett 2021 Apr 10. Epub 2021 Apr 10.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Aurora inase A (AURKA) regulates apoptosis and autophagy in various diseases and has shown promising clinical effects. Nevertheless, the complex regulatory mechanism of AURKA and autophagy in non-small-cell lung cancer (NSCLC) radiosensitivity remains to be elucidated. Here, we showed that AURKA was upregulated in NSCLC cell lines and tissues and that AURKA overexpression was significantly related to a poor prognosis, tumor stage and lymph node metastasis in NSCLC. Read More

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Strain Construction for Intracellular Metabolic Pathway Localization in Y. lipolytica.

Methods Mol Biol 2021 ;2307:147-157

Environmental and Molecular Sciences Laboratory, PNNL, Richland, WA, USA.

Pathway localization by fluorophore or epitope tagging can be accomplished through a multi-staged DNA construct and confirmation process, to generate a series of successfully tagged protein targets. Prerequisite conditions for this process in Y. lipolytica are auxotrophic selection (leu2 or ura3), impaired non-homologous end joining by deletion or impairment of ku70, and plasmids or gene pieces for epitope-selection cassette construction. Read More

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January 2021

Hematopoietic Cell Kinase (HCK) Is a Player of the Crosstalk Between Hematopoietic Cells and Bone Marrow Niche Through CXCL12/CXCR4 Axis.

Front Cell Dev Biol 2021 25;9:634044. Epub 2021 Mar 25.

Hematology and Transfusion Medicine Center-University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, Brazil.

The crosstalk between hematopoietic stem/progenitor cells (HSC), both normal and leukemic, and their neighboring bone marrow (BM) microenvironment (niche) creates a reciprocal dependency, a master regulator of biological process, and chemotherapy resistance. In acute myeloid leukemia (AML), leukemic stem/progenitor cells (LSC) anchored in the protective BM microenvironment, reprogram and transform this niche into a leukemia-supporting and chemoprotective environment. One most important player involved in this crosstalk are CXCL12, produced by the BM mesenchymal stromal cells, and its receptor CXCR4, present onto HSC. Read More

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Insulin Resistance and Pellino-1 Mediated Decrease in the Activities of Vasodilator Signaling Contributes to Sunitinib-Induced Hypertension.

Front Pharmacol 2021 25;12:617165. Epub 2021 Mar 25.

Departments of Cardiology and Clinical Pharmacy, Harbin Medical University Cancer Hospital, Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Heilongjiang key laboratory for Metabolic disorder and cancer related cardiovascular diseases, and Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin, China.

Antiangiogenic tyrosine kinases inhibitors induce hypertension, which may increase the incidents of cardiovascular complications and limit their use. However, the mechanisms by which usage of TKIs results in hypertension have not been fully understood. Here, we report the potential mechanisms of how sunitinib, a widely used TKI, induces hypertension. Read More

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The Role of Mitochondrial Adaptation and Metabolic Flexibility in the Pathophysiology of Obesity and Insulin Resistance: an Updated Overview.

Curr Obes Rep 2021 Apr 10. Epub 2021 Apr 10.

First Department of Propaedeutic Internal Medicine, School of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Purpose Of Review: The term "metabolic flexibility" denotes the dynamic responses of the cellular oxidative machinery in order to adapt to changes in energy substrate availability. A progressive loss of this adaptive capacity has been implicated in the development of obesity-related comorbidities. Mitochondria are dynamic intracellular organelles which play a fundamental role in energy metabolism, and the mitochondrial adaptation to environmental challenges may be viewed as the functional component of metabolic flexibility. Read More

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Glucotoxicity-induced suppression of Cox6a2 expression provokes β-cell dysfunction via augmented ROS production.

Biochem Biophys Res Commun 2021 Apr 8;556:134-141. Epub 2021 Apr 8.

Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita City, Osaka, 565-0871, Japan.

Oxidative stress is a deteriorating factor for pancreatic β-cells under chronic hyperglycemia in diabetes. However, the molecular mechanism underlying the increase in oxidative stress in β-cells under diabetic conditions remains unclear. We demonstrated previously that the selective alleviation of glucotoxicity ameliorated the downregulation of several β-cell factors, including Cox6a2. Read More

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Association of triglyceride-glucose index and lung health: a population-based study.

Chest 2021 Apr 8. Epub 2021 Apr 8.

Section of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX.

Background: Metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease. The triglyceride-glucose index (TyG), a measure of metabolic dysfunction, is associated with metabolic syndrome and insulin resistance, but its relationship to lung health is unknown.

Research Question: What is the relationship of TyG to respiratory symptoms, chronic lung disease, and lung function?

Study Design: and Methods: We analyzed the National Health and Nutrition Examination Survey from 1999-2012. Read More

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Insights into intrauterine growth restriction based on maternal and umbilical cord blood metabolomics.

Sci Rep 2021 Apr 9;11(1):7824. Epub 2021 Apr 9.

Institute of Chemical Biology, National Hellenic Research Foundation, Athens, Greece.

Intrauterine growth restriction (IUGR) is a fetal adverse condition, ascribed by limited oxygen and nutrient supply from the mother to the fetus. Management of IUGR is an ongoing challenge because of its connection with increased fetal mortality, preterm delivery and postnatal pathologies. Untargeted nuclear magnetic resonance (H NMR) metabolomics was applied in 84 umbilical cord blood and maternal blood samples obtained from 48 IUGR and 36 appropriate for gestational age (AGA) deliveries. Read More

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Enhanced antibacterial activity of a novel biocompatible triarylmethane based ionic liquid-graphene oxide nanocomposite.

Colloids Surf B Biointerfaces 2021 Mar 26;203:111729. Epub 2021 Mar 26.

Department of Chemistry, Amity Institute of Applied Sciences, Amity University Kolkata, Major Arterial Road, Action Area II, Kadampukur Village, Rajarhat, Newtown, West Bengal, 700135, India. Electronic address:

Biofilm formation on medical implants and devices has been a severe concern that results in their impaired performance and life-threatening complications. Thus, development of novel functional coatings for infection prone surfaces with biofilm inhibiting characteristics is of prime significance considering the rapid emergence of multidrug resistant bacteria. Herein we present a novel nanocomposite derived from Graphene Oxide (GO) and a newly developed functional Ionic liquid (IL) obtained through a metathesis reaction between a triarylmethane dye hexamethyl pararosaniline chloride or crystal violet (CV) and sodium dodeceyl sulfate (SDS) to yield [CV][DS] (hexamethyl pararosaniline dodecyl sulfate). Read More

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Anisotropic Conductive Reduced Graphene Oxide/Silk Matrices Promote Post-Infarction Myocardial Function by Restoring Electrical Integrity.

Acta Biomater 2021 Apr 6. Epub 2021 Apr 6.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technology, Xi'an Jiaotong University, Xi'an 710049, Shannxi, P.R. China. Electronic address:

Myocardial infarction (MI) remains the leading cause of death globally, often leading to impaired cardiac function and pathological myocardial microenvironment. Electrical conduction abnormalities of the infarcted myocardium not only induce adverse myocardial remodeling but also prevent tissue repair. Restoring the myocardial electrical integrity, particularly the anisotropic electrical signal propagation within the injured area after infarction is crucial for an effective function recovery. Read More

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increased drought resistance 1 Mutation Increases Drought Tolerance Of Upland Rice By Altering Physiological And Morphological Traits And Limiting ROS Levels.

Plant Cell Physiol 2021 Apr 9. Epub 2021 Apr 9.

College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China.

To discover new mutants conferring enhanced tolerance to drought stress, we screened a mutagenized upland rice (O. sativa) population (cv. IAPAR9) and identified a mutant, named idr1-1 (increased drought resistance 1-1), with obviously increased drought tolerance under upland field conditions. Read More

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High phosphate impairs arterial endothelial function through AMPK-related pathways in mouse resistance arteries.

Acta Physiol (Oxf) 2021 Apr 20;231(4):e13595. Epub 2020 Dec 20.

Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.

Aims: In patients with renal disease, high serum phosphate shows a relationship with cardiovascular risk. We speculate that high phosphate (HP) impairs arterial vasodilation via the endothelium and explore potential underlying mechanisms.

Methods: Isolated vessel relaxation, endothelial function, glomerular filtration rate (GFR), oxidative stress status and protein expression were assessed in HP diet mice. Read More

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Tumor Microenvironment Proteomics: Lessons From Multiple Myeloma.

Front Oncol 2021 23;11:563384. Epub 2021 Mar 23.

Department of Experimental and Clinical Oncology, Discipline of Hematology and Hemotherapy, Federal University of São Paulo, UNIFESP, São Paulo, Brazil.

Although the "seed and soil" hypothesis was proposed by Stephen Paget at the end of the 19th century, where he postulated that tumor cells (seeds) need a propitious medium (soil) to be able to establish metastases, only recently the tumor microenvironment started to be more studied in the field of Oncology. Multiple myeloma (MM), a malignancy of plasma cells, can be considered one of the types of cancers where there is more evidence in the literature of the central role that the bone marrow (BM) microenvironment plays, contributing to proliferation, survival, migration, and drug resistance of tumor cells. Despite all advances in the therapeutic arsenal for MM treatment in the last years, the disease remains incurable. Read More

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Molecular mechanisms of lipotoxicity-induced pancreatic β-cell dysfunction.

Int Rev Cell Mol Biol 2021 12;359:357-402. Epub 2021 Mar 12.

Department of Molecular Biophysics, Biofisika Institute (University of Basque Country and Consejo Superior de Investigaciones Científicas (UPV/EHU, CSIC)), Leioa, Spain; Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Leioa, Spain. Electronic address:

Type 2 diabetes (T2D), a heterogeneous disorder derived from metabolic dysfunctions, leads to a glucose overflow in the circulation due to both defective insulin secretion and peripheral insulin resistance. One of the critical risk factor for T2D is obesity, which represents a global epidemic that has nearly tripled since 1975. Obesity is characterized by chronically elevated free fatty acid (FFA) levels, which cause deleterious effects on glucose homeostasis referred to as lipotoxicity. Read More

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Dietary Selenium Requirement for the Prevention of Glucose Intolerance and Insulin Resistance in Middle-Aged Mice.

J Nutr 2021 Apr 8. Epub 2021 Apr 8.

Department of Food Science, Nutrition, and Health Promotion, Mississippi State University, Mississippi State, MS, USA.

Background: Although dietary selenium (Se) deficiency or excess induces type 2 diabetes-like symptoms in mice, suboptimal body Se status usually causes no symptoms but may promote age-related decline in overall health.

Objectives: We sought to determine the dietary Se requirement for protection against type 2 diabetes-like symptoms in mice.

Methods: Thirty mature (aged 4 mo) male C57BL/6J mice were fed a Se-deficient torula yeast AIN-93M diet supplemented with Na2SeO4 in graded concentrations totaling 0. Read More

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COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography.

J Thromb Thrombolysis 2021 Apr 7. Epub 2021 Apr 7.

Department of Anesthesiology, Emory University Hospital, Emory University School of Medicine, 3rd Floor, 1364 Clifton Rd, NE, Atlanta, GA, 30322, USA.

Patients critically ill with COVID-19 are at risk for thrombotic events despite prophylactic anticoagulation. Impaired fibrinolysis has been proposed as an underlying mechanism. Our objective was to determine if fibrinolysis stimulated by tissue plasminogen activator (tPA) differed between COVID patients and controls. Read More

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Metabolic adaptation characterizes short-term resistance to weight loss induced by a low-calorie diet in overweight/obese individuals.

Am J Clin Nutr 2021 Apr 7. Epub 2021 Apr 7.

Translational Research Institute, AdventHealth, Orlando, FL, USA.

Background: Low-calorie diet (LCD)-induced weight loss demonstrates response heterogeneity. Physiologically, a decrease in energy expenditure lower than what is predicted based on body composition (metabolic adaptation) and/or an impaired capacity to increase fat oxidation may hinder weight loss. Understanding the metabolic components that characterize weight loss success is important for optimizing weight loss strategies. Read More

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Polycystic Ovary Syndrome: the Epigenetics Behind the Disease.

Reprod Sci 2021 Apr 7. Epub 2021 Apr 7.

Department of Gynecology and Obstetrics, Ribeirao Preto Medical School, University of Sao Paulo, Av Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, SP, Brazil.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting approximately 5-20% of women of reproductive age. PCOS is a multifactorial, complex, and heterogeneous disease, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries, which may lead to impaired fertility. Besides the reproductive outcomes, multiple comorbidities, such as metabolic disturbances, insulin resistance, obesity, diabetes, and cardiovascular disease, are associated with PCOS. Read More

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Diabetes Mellitus due to Toxic Misfolding of Proinsulin Variants.

Mol Metab 2021 Apr 3:101229. Epub 2021 Apr 3.

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis IN 46202 USA. Electronic address:

Dominant mutations in the human insulin gene (INS) lead to pancreatic β-cell dysfunction and diabetes mellitus (DM) due to toxic misfolding of a mutant proinsulin. Analogous to a classical mouse model of monogenic DM ("Akita"), this syndrome highlights the susceptibility of β-cells to endoreticulum (ER) stress due to protein misfolding and aberrant aggregation. Diverse clinical mutations directly or indirectly perturb native disulfide pairing. Read More

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Population structure, case clusters, and genetic lesions associated with Canadian Salmonella 4,[5],12:i:- isolates.

PLoS One 2021 6;16(4):e0249079. Epub 2021 Apr 6.

Division of Enteric Diseases, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.

Monophasic Salmonella 4,[5]:12:i:- are a major public health problem because they are one of the top five Salmonella serotypes isolated from clinical cases globally and because they can carry resistance to multiple antibiotics. A total of 811 Salmonella 4,[5]:12:i:- and S. Typhimurium whole genome sequences (WGS) were generated. Read More

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Anti-cancer activity and in vitro to in vivo mechanistic recapitulation of novel ruthenium-based metallodrugs in the zebrafish model.

Toxicol Sci 2021 Apr 3. Epub 2021 Apr 3.

Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08854, United States.

Ruthenium is popular as a metal-core for chemotherapeutics, due to versatile molecular coordination. Because new metallodrugs are synthesized at high rates, our studies included assays in zebrafish to expedite the initial evaluation as anti-cancer agents. Here we evaluated novel metallodrugs PMC79 and LCR134), and cisplatin, a widely-used platinum-based chemotherapeutic. Read More

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The fatty acid elongase ELOVL6 regulates bortezomib resistance in multiple myeloma.

Blood Adv 2021 Apr;5(7):1933-1946

Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC.

Resistance to the proteasome inhibitor bortezomib (BTZ) represents a major obstacle in the treatment of multiple myeloma (MM). The contribution of lipid metabolism in the resistance of MM cells to BTZ is mostly unknown. Here we report that levels of fatty acid elongase 6 (ELOVL6) were lower in MM cells from BTZ-nonresponsive vs BTZ-responsive patients and in cultured MM cells selected for BTZ resistance compared with parental counterparts. Read More

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A small cysteine-rich phytotoxic protein of Phytophthora capsici functions as both plant defense elicitor and virulence factor.

Mol Plant Microbe Interact 2021 Apr 5. Epub 2021 Apr 5.

Yangzhou University, 38043, Plant Pathology, 48 Wenhui Eastern Rd, Yangzhou, Jiangsu Province, China, 225009.

Small cysteine-rich (SCR) proteins including fungal avirulence proteins play important roles in the pathogen-plant interactions. SCR protein-encoding genes have been discovered in the genomes of Phytophthora pathogens, but their functions during the pathogenesis remain obscure. Here, we report the characterization of one Phytophthora capsici SCR protein, namely SCR82 with similarity to Phytophthora cactorum phytotoxic protein PcF. Read More

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Inhibition of HSP90 as a Strategy to Radiosensitize Glioblastoma: Targeting the DNA Damage Response and Beyond.

Front Oncol 2021 17;11:612354. Epub 2021 Mar 17.

Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Radiotherapy is an essential component of multi-modality treatment of glioblastoma (GBM). However, treatment failure and recurrence are frequent and give rise to the dismal prognosis of this aggressive type of primary brain tumor. A high level of inherent treatment resistance is considered to be the major underlying reason, stemming from constantly activated DNA damage response (DDR) mechanisms as a consequence of oncogene overexpression, persistent replicative stress, and other so far unknown reasons. Read More

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Long non-coding RNA receptor activator of nuclear factor-κ B ligand promotes cisplatin resistance in non-small cell lung cancer cells.

Exp Ther Med 2021 May 22;21(5):518. Epub 2021 Mar 22.

Department of Radiotherapy, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China.

Non-small cell lung cancer (NSCLC) is a common malignancy associated with poor clinical outcomes and high mortality rate. The association between NSCLC development and long non-coding RNA (lncRNA) expression remains to be elucidated. The current study investigated the role of a novel lncRNA, receptor activator of nuclear factor-κ B ligand (RANKL), in the resistance of NSCLC to chemotherapy. Read More

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Sphingolipids as a Culprit of Mitochondrial Dysfunction in Insulin Resistance and Type 2 Diabetes.

Front Endocrinol (Lausanne) 2021 18;12:635175. Epub 2021 Mar 18.

Department of Medical Biology, Medical University of Bialystok, Bialystok, Poland.

Insulin resistance is defined as a complex pathological condition of abnormal cellular and metabolic response to insulin. Obesity and consumption of high-fat diet lead to ectopic accumulation of bioactive lipids in insulin-sensitive tissues. Intracellular lipid accumulation is regarded as one of the major factors in the induction of insulin resistance and type 2 diabetes (T2D). Read More

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