289,791 results match your criteria endogenous

Thrombin generation is associated with ischemic stroke at a young age.

Thromb Res 2021 Mar 29;202:139-144. Epub 2021 Mar 29.

Erasmus MC, University Medical Center Rotterdam, Department of Hematology, the Netherlands. Electronic address:

Introduction: Understanding the underlying mechanisms in ischemic stroke (IS) in young adults remains challenging. Thrombin activates processes that contribute to the development and progression of arterial diseases. We investigated the association between thrombin generation (TG) and a first IS or transient ischemic attack (TIA) in young adults. Read More

View Article and Full-Text PDF

Effects of dim artificial light at night on locomotor activity, cardiovascular physiology, and circadian clock genes in a diurnal songbird.

Environ Pollut 2021 Mar 31;282:117036. Epub 2021 Mar 31.

Department of Biology, University of Nevada, Reno, Reno, NV, USA.

Artificial light is transforming the nighttime environment and quickly becoming one of the most pervasive pollutants on earth. Across taxa, light entrains endogenous circadian clocks that function to synchronize behavioral and physiological rhythms with natural photoperiod. Artificial light at night (ALAN) disrupts these photoperiodic cues and has consequences for humans and wildlife including sleep disruption, physiological stress and increased risk of cardiovascular disease. Read More

View Article and Full-Text PDF

Identification of inference fallacies in solid waste generation estimations of developing countries. A case-study in Panama.

Waste Manag 2021 Apr 7;126:454-465. Epub 2021 Apr 7.

Institut de Ciència i Tecnologia Ambientals, Universitat Autònoma de Barcelona, Bellaterra, Spain; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

The absence of sound sampling procedures and statistical analyses to estimate solid waste generation in many developing countries has resulted in incomplete historical records of waste quantity and composition. Data is often arbitrarily aggregated or disaggregated as a function of waste generators to obtain results at the desired spatial level of analysis. Inference fallacies arising from the generalization or individualization of results are almost never considered. Read More

View Article and Full-Text PDF

A Brief History of Carbon Monoxide and Its Therapeutic Origins.

Nitric Oxide 2021 Apr 7. Epub 2021 Apr 7.

Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

It is estimated that 10% of carbon throughout the cosmos is in the form of carbon monoxide (CO) [1]. Earth's earliest prebiotic atmosphere included the trinity of gasotransmitters CO, nitric oxide (NO), and hydrogen sulfide (HS), for which all of life has co-evolved with [2]. Speculation for extraterrestrial life in harsh environments is similarly based on harnessing atmospheric CO as a primary energy source [3]. Read More

View Article and Full-Text PDF

Prolyl Oligopeptidase Inhibition Reduces Oxidative Stress via Reducing NADPH Oxidase Activity by Activating Protein Phosphatase 2A.

Free Radic Biol Med 2021 Apr 7. Epub 2021 Apr 7.

Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, FINLAND; Integrative Physiology and Pharmacology Unit, Institute of Biotechnology, Faculty of Medicine, University of Turku, FINLAND; School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, FINLAND. Electronic address:

Oxidative stress (OS) is a common toxic feature in various neurodegenerative diseases. Therefore, reducing OS could provide a potential approach to achieve neuroprotection. Prolyl oligopeptidase (PREP) is a serine protease that is linked to neurodegeneration, as endogenous PREP inhibits autophagy and induces the accumulation of detrimental protein aggregates. Read More

View Article and Full-Text PDF

Regulation of Nuclear Factor-KappaB (NF-κB) signaling pathway by non-coding RNAs in cancer: Inhibiting or promoting carcinogenesis?

Cancer Lett 2021 Apr 7. Epub 2021 Apr 7.

NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117 600, Singapore. Electronic address:

The nuclear factor-kappaB (NF-κB) signaling pathway is considered as a potential therapeutic target in cancer therapy. It has been well established that transcription factor NF-κB is involved in regulating physiological and pathological events including inflammation, immune response and differentiation. Increasing evidences suggest that deregulated NF-κB signaling can enhance cancer cell proliferation, metastasis and also mediate radio-as well as chemo-resistance. Read More

View Article and Full-Text PDF

Agmatine has beneficial effect on harmaline-induced essential tremor in rat.

Neurosci Lett 2021 Apr 7:135881. Epub 2021 Apr 7.

Kocaeli University, Faculty of Medicine, Department of Physiology, Kocaeli, Turkey. Electronic address:

Essential tremor (ET) is one of the most prevalent movement disorders and the most common cause of abnormal tremors. However, it cannot be treated efficiently with the currently available pharmacotherapy options. The pathophysiology of harmaline-induced tremor, most commonly used model of ET, involves various neurotransmitter systems including glutamate as well as ion channels. Read More

View Article and Full-Text PDF

Starch-lipid interaction alters the molecular structure and ultimate starch bioavailability: A comprehensive review.

Int J Biol Macromol 2021 Apr 7. Epub 2021 Apr 7.

Division of Biochemistry, ICAR - Indian Agricultural Research Institute (IARI), New Delhi 110012, India. Electronic address:

Starch bioavailability which results in eliciting postprandial glycaemic response, is a trait of great significance and is majorly influenced by the physical interaction among the matrix components governed by their molecular structure as well as dynamics. Among physical interactions limiting starch bioavailability, starch and any guest molecules like lipid interact together to alter the molecular structure into a compact V-type arrangement endorsing the processed crystallinity, thus limiting carbolytic enzymatic digestion and further bioavailability. Considering the importance of starch-lipid dynamics affecting bioavailability, intensive research based on endogenous (internal lipids which are embedded into the food matrix) as well as exogenous (those are added from outside into the food matrix during processing like cooking) lipids have been carried out, endorsing physical interactions at colloidal and microstructural levels. Read More

View Article and Full-Text PDF

Preparation of the peroxisome proliferator-activated receptor α polyclonal antibody: Its application in fatty liver hemorrhagic syndrome.

Int J Biol Macromol 2021 Apr 7. Epub 2021 Apr 7.

Jiangxi Provincial Key Laboratory for Animal Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, Jiangxi, China. Electronic address:

Peroxisome proliferator-activated receptor α (PPARα) play a key role in the regulation of metabolic homeostasis, inflammation, cellular growth, and differentiation. To further explore the potential role of PPARα in the energy homeostasis of fatty liver hemorrhagic syndrome (FLHS), we reported the prokaryotic expression and purification of chicken PPARα subunit protein, and successfully prepared a polyclonal antibody against PPARα recombinant protein. The 987 bp PPARα subunit genes were cloned into the pEASY-T3 clone vector. Read More

View Article and Full-Text PDF

Metformin leads to accumulation of reactive oxygen species by inhibiting the NFE2L1 expression in human hepatocellular carcinoma cells.

Toxicol Appl Pharmacol 2021 Apr 7:115523. Epub 2021 Apr 7.

School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China. Electronic address:

Metformin, as the first-line drug for the treatment of type 2 diabetes mellitus, has been shown to possess a capability to activate or inhibit the production of reactive oxygen species (ROS) in different ways. However, the detailed mechanisms of the opposite effect are poorly understood. Here we provide evidence that metformin induces accumulation of ROS by inhibiting the expression of a core antioxidant transcription factor nuclear factor erythroid 2 like 1 (NFE2L1/Nrf1) in human hepatocellular carcinoma HepG2 cells. Read More

View Article and Full-Text PDF

Structural basis of drug recognition by the multidrug transporter ABCG2.

J Mol Biol 2021 Apr 7:166980. Epub 2021 Apr 7.

Institute of Molecular Biology and Biophysics, ETH Zurich, Switzerland. Electronic address:

ABCG2 is an ATP-binding cassette (ABC) transporter whose function affects the pharmacokinetics of drugs and contributes to multidrug resistance of cancer cells. While its interaction with the endogenous substrate estrone-3-sulfate (ES) has been elucidated at a structural level, the recognition and recruitment of exogenous compounds is not understood at sufficiently high resolution. Here we present three cryo-EM structures of nanodisc-reconstituted, human ABCG2 bound to anticancer drugs tariquidar, topotecan and mitoxantrone. Read More

View Article and Full-Text PDF

Prognostic value of total testosterone levels in patients with acute coronary syndromes.

Eur J Prev Cardiol 2021 Apr;28(2):235-242

Cardiology Division, Geneva University Hospitals, Switzerland.

Background: Endogenous testosterone levels decrease in men with aging. Controversies persist regarding the screening and treatment of low testosterone levels in patients with acute coronary syndromes (ACS).

Methods And Results: Total serum testosterone levels were measured in 1054 men hospitalized for ACS that were part of a Swiss prospective cohort. Read More

View Article and Full-Text PDF

An ultra-high affinity protein-protein interface displaying sequence-robustness.

Protein Sci 2021 Apr 10. Epub 2021 Apr 10.

Biochemistry and Structural Biology, Lund University, Lund, Sweden.

Protein-protein interactions are crucial in biology and play roles in for example, the immune system, signalling pathways, and enzyme regulation. Ultra-high affinity interactions (K , <0.1 nM) occur in these systems, however, structures and energetics behind stability of ultra-high affinity protein-protein complexes are not well understood. Read More

View Article and Full-Text PDF

Long non-coding RNA MFAT1 promotes skeletal muscle fibrosis by modulating the miR-135a-5p-Tgfbr2/Smad4 axis as a ceRNA.

J Cell Mol Med 2021 Apr 9. Epub 2021 Apr 9.

Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Fibrosis after skeletal muscle injury is common in sports and can cause irreversible damage to the biomechanical properties of skeletal muscle. Long non-coding RNAs (lncRNAs) have been validated to act as important modulators in the fibrosis of various organs. Here, we reported a novel lncRNA (the skeletal muscle fibrosis-associated transcript 1, lnc-MFAT1), which was highly expressed in skeletal muscle fibrosis. Read More

View Article and Full-Text PDF

A liquid culture cancer spheroid model reveals low PI3K/Akt pathway activity and low adhesiveness to the extracellular matrix.

FEBS J 2021 Apr 9. Epub 2021 Apr 9.

Faculty of Health Sciences, University of Bristol, Bristol, UK.

Three-dimensional (3D) cultures of cancer cells in liquid without extracellular matrix (ECM) offers in vitro models for metastasising conditions such as those in vessels and effusion. However, liquid culturing is often hindered by cell adhesiveness, which causes large cell clumps. We previously described a liquid culture material, LA717, which prevents non-clonal cell adhesion and subsequent clumping, thus allowing clonal growth of spheroids in an anchorage-independent manner. Read More

View Article and Full-Text PDF

Iso-anchorene is an endogenous metabolite that inhibits primary root growth in Arabidopsis.

Plant J 2021 Apr 10. Epub 2021 Apr 10.

King Abdullah University of Science and Technology (KAUST), Biological and Environmental Sciences and Engineering Division, Center for Desert Agriculture, The BioActives Lab, Thuwal, 23955-6900, Saudi Arabia.

Carotenoid-derived regulatory metabolites and hormones are generally known to arise through the oxidative cleavage of a single double bond in the carotenoid backbone, which yields mono-carbonyl products called apocarotenoids. However, the extended conjugated double bond system of these pigments predestines them also to repeated cleavage forming di-aldehyde products, diapocarotenoids, which have been less investigated due to their instability and low abundance. Recently, we reported on the short diapocarotenoid anchorene as an endogenous Arabidopsis metabolite and specific signaling molecule that promotes anchor root formation. Read More

View Article and Full-Text PDF

LINC01123 enhances osteosarcoma cell growth by activating the Hedgehog pathway via the miR-516b-5p/Gli1 axis.

Cancer Sci 2021 Apr 10. Epub 2021 Apr 10.

Department of Orthopedics, The Affiliated Hospital of Nanjing Medical University, People's Hospital, Changzhou, Jiangsu, 213003, China.

The lncRNA LINC01123 has been reported to act as an oncogene in many human cancers. Nevertheless, the function and underlying mechanism of LINC01123 in osteosarcoma (OS) remain unclear. This study aimed to explore the roles and mechanisms of LINC01123 in OS progression. Read More

View Article and Full-Text PDF

A Ratiometric Fluorescent Biosensor Reveals Dynamic Regulation of Long-Chain Fatty Acyl-CoA Esters Metabolism.

Angew Chem Int Ed Engl 2021 Apr 10. Epub 2021 Apr 10.

Central China Normal University, Chemistry, CHINA.

Despite increasing awareness of the biological impacts of long-chain fatty acyl-CoA esters (LCACoAs), our knowledge about the subcellular distribution and regulatory functions of these acyl-CoA molecules is limited by a lack of methods for detecting LCACoAs in living cells. Here, we report development of a genetically encoded fluorescent sensor that enables ratiometric quantification of LCACoAs in living cells and subcellular compartments. We demonstrate how this FadR-cpYFP fusion "LACSer sensor" undergoes LCACoA-induced conformational changes reflected in easily detectable fluorescence responses, and show proof-of-concept for real-time monitoring of LCACoAs in human cells. Read More

View Article and Full-Text PDF

PolyQ-expanded proteins impair cellular proteostasis of ataxin-3 through sequestering the co-chaperone HSJ1 into aggregates.

Sci Rep 2021 Apr 9;11(1):7815. Epub 2021 Apr 9.

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, People's Republic of China.

Polyglutamine (polyQ) expansion of proteins can trigger protein misfolding and amyloid-like aggregation, which thus lead to severe cytotoxicities and even the respective neurodegenerative diseases. However, why polyQ aggregation is toxic to cells is not fully elucidated. Here, we took the fragments of polyQ-expanded (PQE) ataxin-7 (Atx7) and huntingtin (Htt) as models to investigate the effect of polyQ aggregates on the cellular proteostasis of endogenous ataxin-3 (Atx3), a protein that frequently appears in diverse inclusion bodies. Read More

View Article and Full-Text PDF

Role of a thrombin generation assay in the prediction of infection severity.

Sci Rep 2021 Apr 9;11(1):7814. Epub 2021 Apr 9.

Department of Internal Medicine C, Emek Medical Center, Afula, Israel.

Thrombin plays a central role in sepsis pathophysiology. The correlation of thrombin generation (TG) assays with infection severity and prognosis, and whether it can be used as a clinical tool, have been poorly explored and are the subjects of our research. We recruited 130 patients with systemic infection between 2016 and 2019. Read More

View Article and Full-Text PDF

Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice.

Nat Commun 2021 Apr 9;12(1):2121. Epub 2021 Apr 9.

RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.

Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor DNA as a template. PEs facilitate nucleotide substitutions or local insertions or deletions within the genome based on the template sequence encoded within the prime editing guide RNA (pegRNA). However, the efficacy of prime editing in adult mice has not been established. Read More

View Article and Full-Text PDF

IFNg is Critical for CAR T Cell Mediated Myeloid Activation and Induction of Endogenous Immunity.

Cancer Discov 2021 Apr 9. Epub 2021 Apr 9.

Cancer Immunotherapy & Tumor Immunology and Hematology & Hematopoietic Cell Transplantation, Beckman Research Institute of the City of Hope Comprehensive Cancer Center

Chimeric antigen receptor (CAR) T cells mediate potent antigen-specific antitumor activity, however, their indirect effects on the endogenous immune system is not well characterized. Remarkably, we demonstrate that CAR T cell treatment of mouse syngeneic glioblastoma activates intratumoral myeloid cells and induces endogenous T cell memory responses coupled with feed-forward propagation of CAR T responses. IFNy production by CAR T cells and IFNy-responsiveness of host immune cells is critical for tumor immune landscape remodeling to promote a more activated and less suppressive tumor microenvironment. Read More

View Article and Full-Text PDF

Characteristics of insulinopenic and non insulinopenic diabetes related to immune checkpoint inhibitors: A French pharmacovigilance study.

Therapie 2021 Mar 24. Epub 2021 Mar 24.

Regional Pharmacovigilance Center, Department of Pharmacology, Pitié-Salpêtrière Hospital, 47-83, boulevard de l'Hôpital, 75013 Paris, France. Electronic address:

Introduction: Immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) is an immune-related adverse drug reaction (irADR). Hyperglycemia can be linked to endogenous insulin deficiency with ketoacidosis or associated with preserved beta-cell function.

Objectives: We aimed to identify the characteristics of both types of ICI-DM (type 1 and type 2 DM), to improve our understanding of this irADR and its management. Read More

View Article and Full-Text PDF

Comprehensive analyses of correlation and survival reveal informative lncRNA prognostic signatures in colon cancer.

World J Surg Oncol 2021 Apr 9;19(1):104. Epub 2021 Apr 9.

School of Computer Science and Engineering, Northwestern Polytechnical University, Xi'an, People's Republic of China.

Background: Colon cancer is a commonly worldwide cancer with high morbidity and mortality. Long non-coding RNAs (lncRNAs) are involved in many biological processes and are closely related to the occurrence of colon cancer. Identification of the prognostic signatures of lncRNAs in colon cancer has great significance for its treatment. Read More

View Article and Full-Text PDF

OTULIN is a new target of EA treatment in the alleviation of brain injury and glial cell activation via suppression of the NF-κB signalling pathway in acute ischaemic stroke rats.

Mol Med 2021 Apr 9;27(1):37. Epub 2021 Apr 9.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Objective: Ovarian tumour domain deubiquitinase with linear linkage specificity (OTULIN) is a potent negative regulator of the nuclear factor-κB (NF-κB) signalling pathway, and it plays a strong neuroprotective role following acute ischemic stroke. Electroacupuncture (EA) is an effective adjuvant treatment for reducing brain injury and neuroinflammation via the inhibition of NF-κB p65 nuclear translocation, but the underlying mechanism is not clear. The present study investigated whether OTULIN was necessary for EA to mitigate brain injury and glial cell activation in a transient middle cerebral artery occlusion (tMCAO) model in rats. Read More

View Article and Full-Text PDF

Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Vascular Physiology, National Cerebral and Cardiovascular Center Research Institute, 564-8565 Suita, Japan;

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by arteriopathy in the small to medium-sized distal pulmonary arteries, often accompanied by infiltration of inflammatory cells. Aryl hydrocarbon receptor (AHR), a nuclear receptor/transcription factor, detoxifies xenobiotics and regulates the differentiation and function of various immune cells. However, the role of AHR in the pathogenesis of PAH is largely unknown. Read More

View Article and Full-Text PDF

Improved photosynthetic capacity and photosystem I oxidation via heterologous metabolism engineering in cyanobacteria.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

MSU-DOE Plant Research Laboratory, Michigan State University, East Lansing, MI 48824;

Cyanobacteria must prevent imbalances between absorbed light energy (source) and the metabolic capacity (sink) to utilize it to protect their photosynthetic apparatus against damage. A number of photoprotective mechanisms assist in dissipating excess absorbed energy, including respiratory terminal oxidases and flavodiiron proteins, but inherently reduce photosynthetic efficiency. Recently, it has been hypothesized that some engineered metabolic pathways may improve photosynthetic performance by correcting source/sink imbalances. Read More

View Article and Full-Text PDF

Enhanced cytarabine-induced killing in OGG1-deficient acute myeloid leukemia cells.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239;

Human clinical trials suggest that inhibition of enzymes in the DNA base excision repair (BER) pathway, such as PARP1 and APE1, can be useful in anticancer strategies when combined with certain DNA-damaging agents or tumor-specific genetic deficiencies. There is also evidence suggesting that inhibition of the BER enzyme 8-oxoguanine DNA glycosylase-1 (OGG1), which initiates repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy-dG), could be useful in treating certain cancers. Specifically, in acute myeloid leukemia (AML), both the RUNX1-RUNX1T1 fusion and the CBFB-MYH11 subtypes have lower levels of expression, which correlate with increased therapeutic-induced cell cytotoxicity and good prognosis for improved, relapse-free survival compared with other AML patients. Read More

View Article and Full-Text PDF

Effects of aging on surface properties and endogenous copper and zinc leachability of swine manure biochar and its composite with alkali-fused fly ash.

Waste Manag 2021 Apr 6;126:400-410. Epub 2021 Apr 6.

Guangdong Provincial Key Laboratory of Petrochemical Pollution Processes and Control, School of Environmental Science and Engineering, Guangdong University of Petrochemical Technology, Maoming, Guangdong 525000, PR China. Electronic address:

Biochar aging is a key factor leading to the decline of biochar stability and the release of endogenous pollutants. This study investigated the effects of five artificial and simulated aging processes on the surface properties and endogenous copper (Cu) and zinc (Zn) leachability of swine manure biochar and its composite with alkali-fused fly ash. Aging obviously reduced carbon (C) content on the surface of swine manure biochar and increased oxygen (O) content. Read More

View Article and Full-Text PDF

Melatonin application improves berry coloration, sucrose synthesis, and nutrient absorption in 'Summer Black' grape.

Food Chem 2021 Mar 27;356:129713. Epub 2021 Mar 27.

College of Horticulture, Sichuan Agricultural University, Chengdu 611130, China. Electronic address:

In this study, we investigated the effects of melatonin application on berry coloration, sugar accumulation, and nutrient absorption in 'Summer Black' grapes. Melatonin spraying at 100 μmol L on grapes during veraison induced skin coloration earlier than that in controls, as well as higher transcript abundance of anthocyanin biosynthesis-related genes and transcription factors MYBA1 and MYBA2. Melatonin treatment increased the soluble sugar content, especially of sucrose, by promoting the activity of sucrose phosphate synthase, and also increased endogenous melatonin content and the concentrations of mineral nutrients N, K, Cu, Fe, and Zn in grape berries. Read More

View Article and Full-Text PDF