15,146 results match your criteria possibility inhibition


Modelling the anaerobic digestion of wastewater sludge under sulfate-rich conditions.

Water Environ Res 2021 May 15. Epub 2021 May 15.

Department of Civil Engineering, McMaster University, 1280 Main Street West, JHE 301, Hamilton, Ontario, L8S 4L8, Canada.

Anaerobic digestion (AD) is a biological treatment process to stabilize organic solids and produce biogas. If present, sulfate is reduced to sulfide by anaerobic sulfate-reducing bacteria and the sulfide can be toxic to anaerobic microorganisms. Here the effect of high initial sulfate concentration on AD of wastewater sludge was investigated using lab-scale batch experiments. Read More

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Tenascin-C immobilizes infiltrating T lymphocytes through CXCL12 promoting breast cancer progression.

EMBO Mol Med 2021 May 14:e13270. Epub 2021 May 14.

The Tumor Microenvironment Laboratory, INSERM UMR_S 1109, Faculté de Médecine, Hopital Civil, Institut d'Hématologie et d'Immunologie, Strasbourg, France.

Immune checkpoint therapy, where CD8 tumor infiltrating T lymphocytes (TIL) are reactivated, is a promising anti-cancer treatment approach, yet with low response rates. The extracellular matrix, in particular tenascin-C, may generate barriers for TIL. To investigate this possibility, we used a MMTV-NeuNT and syngeneic mammary gland grafting model derived thereof with engineered tenascin-C levels and observed accumulation of CD8 TIL in tenascin-C-rich stroma. Read More

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Chemical Synthesis and Biological Evaluations of Adiponectin Collagenous Domain Glycoforms.

J Am Chem Soc 2021 May 12. Epub 2021 May 12.

Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong, SAR, P. R. China.

The homogeneously glycosylated 76-amino acid adiponectin collagenous domains (ACDs) with all of the possible 15 glycoforms have been chemically and individually synthesized using stereoselective glycan synthesis and chemical peptide ligation. The following biological and pharmacological studies enabled correlating glycan pattern to function in the inhibition of cancer cell growth as well as the regulation of systemic energy metabolism. In particular, hAdn-WM6877 was tested in detail with different mouse models and it exhibited promising antitumor, insulin sensitizing, and hepatoprotective activities. Read More

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Takayasu's arteritis occurring under TNF blockers in a patient with spondyloarthritis: is it an association or a paradoxical effect?

Reumatologia 2021 9;59(2):111-114. Epub 2021 Feb 9.

Department of Internal Medicine, Sahloul Hospital, University of Sousse, Faculty of Medicine of Sousse, Tunisia.

Coexistence of spondyloarthritis (SpA) and Takayasu's arteritis is not a common finding, but such cases have been discussed, particularly in the context of choice of therapy. Inhibition of inflammation by tumor necrosis factor inhibitors (TNFi) is a key aspect of the treatment of SpA and also positive effects of such treatment in concomitant large vessel vasculitis have been reported. However, TNFi is also associated with the possibility of initiating vasculitis. Read More

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February 2021

Determination of Hypochlorite via Fluorescence Change from Blue to Green Based on 4-(1 H-imidazo [4,5-f] [1,10]-phenanthrolin-2-yl) Benzaldehyde Oxime.

J Fluoresc 2021 May 11. Epub 2021 May 11.

School of Chemistry, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, South China Normal University, Guangzhou, 510006, People's Republic of China.

The new design strategy will provide the possibility for preparing a dynamic sensor by employing the inhibition of C = N isomerization. In this work, the functional probe 4-(1 H-imidazo [4,5-f] [1,10]-phenanthrolin-2-yl) benzaldehyde oxime (compound 4) has been synthesized and such molecule gives rise to blue emission. Due to the incorporation of hypochlorite, the oxime group can be oxidized to the structure of aldehyde. Read More

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Physiological concentrations of cyanide stimulate mitochondrial Complex IV and enhance cellular bioenergetics.

Proc Natl Acad Sci U S A 2021 May;118(20)

Chair of Pharmacology, Faculty of Science and Medicine, University of Fribourg, 1700 Fribourg, Switzerland

In mammalian cells, cyanide is viewed as a cytotoxic agent, which exerts its effects through inhibition of mitochondrial Complex IV (Cytochrome C oxidase [CCOx]). However, the current report demonstrates that cyanide's effect on CCOx is biphasic; low (nanomolar to low-micromolar) concentrations stimulate CCOx activity, while higher (high-micromolar) concentrations produce the "classic" inhibitory effect. Low concentrations of cyanide stimulated mitochondrial electron transport and elevated intracellular adenosine triphosphate (ATP), resulting in the stimulation of cell proliferation. Read More

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Temporal summation of mechanical pain prospectively predicts movement-evoked pain severity in adults with chronic low back pain.

BMC Musculoskelet Disord 2021 May 10;22(1):429. Epub 2021 May 10.

Department of Psychology, University of Alabama at Birmingham, 1300 University Boulevard, Campbell Hall, Suite 237, Birmingham, AL, 35294, USA.

Background: Biopsychosocial factors above and beyond pathoanatomical changes likely contribute to the severity of chronic low back pain. A pro-nociceptive endogenous pain modulatory balance (↓inhibition and ↑facilitation) may be an important contributor to chronic low back pain severity and physical function; however, additional research is needed to address this possibility. The objective of this study was to determine whether quantitative sensory tests of endogenous pain inhibition and facilitation prospectively predict movement-evoked pain and cLBP severity self-reported on a validated questionnaire. Read More

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Myeloid lncRNA LOUP Mediates Opposing Regulatory Effects of RUNX1 and RUNX1-ETO in t(8;21) AML.

Blood 2021 05 10. Epub 2021 May 10.

Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, Massachusetts, United States.

The mechanism underlying cell type-specific gene induction conferred by ubiquitous transcription factors as well as disruptions caused by their chimeric derivatives in leukemia is not well understood. Here we investigate whether RNAs coordinate with transcription factors to drive myeloid gene transcription. In an integrated genome-wide approach surveying for gene loci exhibiting concurrent RNA- and DNA-interactions with the broadly expressed transcription factor RUNX1, we identified the long noncoding RNA LOUP. Read More

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Overcoming challenges of HERG potassium channel liability through rational design: Eag1 inhibitors for cancer treatment.

Med Res Rev 2021 May 4. Epub 2021 May 4.

AG Oncophysiology, Max-Planck Institute for Experimental Medicine, Göttingen, Germany.

Two decades of research have proven the relevance of ion channel expression for tumor progression in virtually every indication, and it has become clear that inhibition of specific ion channels will eventually become part of the oncology therapeutic arsenal. However, ion channels play relevant roles in all aspects of physiology, and specificity for the tumor tissue remains a challenge to avoid undesired effects. Eag1 (K 10. Read More

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How Physiological Targets Can Be Distinguished from Drug-binding Proteins.

Mol Pharmacol 2021 May 3. Epub 2021 May 3.

Molecular and Cellular Biology, Kennesaw State University, United States

Some drugs in clinical trial owe their effectiveness to "off-target" activity. This and other observations raise a possibility that many studies to identify targets of drugs are incomplete. If "off-target" proteins are pharmacologically important it will be worthwhile to identify them early in the development process, for a better understanding of the molecular basis of drug action. Read More

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Inhibition of Jumonji histone demethylases selectively suppresses HER2+ breast leptomeningeal carcinomatosis growth via inhibition of GM-CSF expression.

Cancer Res 2021 May 3. Epub 2021 May 3.

Neurosurgery, City of Hope Medical Center

HER2+ breast leptomeningeal carcinomatosis (HER2+ LC) occurs when tumor cells spread to cerebrospinal fluid-containing leptomeninges surrounding the brain and spinal cord, a complication with a dire prognosis. HER2+ LC remains incurable with few treatment options. Currently, much effort is devoted towards development of therapies that target mutations. Read More

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Small molecule Y-320 stimulates ribosome biogenesis, protein synthesis, and aminoglycoside-induced premature termination codon readthrough.

PLoS Biol 2021 May 3;19(5):e3001221. Epub 2021 May 3.

Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.

Premature termination codons (PTC) cause over 10% of genetic disease cases. Some aminoglycosides that bind to the ribosome decoding center can induce PTC readthrough and restore low levels of full-length functional proteins. However, concomitant inhibition of protein synthesis limits the extent of PTC readthrough that can be achieved by aminoglycosides like G418. Read More

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Investigation of an ALDH1A1-specific inhibitor for suppression of weight gain in a diet-induced mouse model of obesity.

Int J Obes (Lond) 2021 May 1. Epub 2021 May 1.

Department of Comparative Medicine, University of Washington, Seattle, WA, USA.

Background: Retinoic acid (RA) controls diverse physiological functions including weight regulation and energy metabolism. It has been reported that mice lacking ALDH1A1, one of the aldehyde dehydrogenases (ALDH) that synthesize RA, are healthy and resistant to weight gain, raising the possibility that inhibiting this enzyme might treat obesity. We previously demonstrated that treatment with a pan-ALDH1A enzyme inhibitor, WIN18446, suppressed weight gain in mice fed a high-fat diet (HFD), but caused increased hepatic lipidosis and reversible male infertility. Read More

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KLF5-induced BBOX1-AS1 contributes to cell malignant phenotypes in non-small cell lung cancer via sponging miR-27a-5p to up-regulate MELK and activate FAK signaling pathway.

J Exp Clin Cancer Res 2021 Apr 30;40(1):148. Epub 2021 Apr 30.

Department of Geriatric Respiratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Background: Non-small cell lung cancer (NSCLC) is a major histological subtype of lung cancer with high mortality and morbidity. A substantial amount of evidence demonstrates long non-coding RNAs (lncRNA) as critical regulators in tumorigeneis and malignant progression of human cancers. The oncogenic role of BBOX1 anti-sense RNA 1 (BBOX1-AS1) has been reported in several tumors. Read More

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Tetramethylpyrazine Ameliorates Peritoneal Angiogenesis by Regulating VEGF/Hippo/YAP Signaling.

Front Pharmacol 2021 13;12:649581. Epub 2021 Apr 13.

Department of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Angiogenesis of human peritoneal vascular endothelial cells (HPVECs), linked to vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) signaling, is a complication of peritoneal fibrosis (PF). Hippo/YAP signaling interacts with VEGF/VEGFR2 signaling, but the effect on peritoneal angiogenesis and PF has not been studied. We tested VEGF/Hippo/YAP inhibition by tetramethylpyrazine (TMP) in PF mice and HPVECs. Read More

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A Soluble Epoxide Hydrolase Inhibitor, 1-TrifluoromethoxyPhenyl-3-(1-Propionylpiperidin-4-yl) Urea, Ameliorates Experimental Autoimmune Encephalomyelitis.

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.

Polyunsaturated fatty acids (PUFAs) are essential FAs for human health. Cytochrome P450 oxygenates PUFAs to produce anti-inflammatory and pain-resolving epoxy fatty acids (EpFAs) and other oxylipins whose epoxide ring is opened by the soluble epoxide hydrolase (sEH/), resulting in the formation of toxic and pro-inflammatory vicinal diols (dihydroxy-FAs). Pharmacological inhibition of sEH is a promising strategy for the treatment of pain, inflammation, cardiovascular diseases, and other conditions. Read More

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Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3'-Disulfate.

Molecules 2021 Apr 13;26(8). Epub 2021 Apr 13.

Institute of Biomedical Chemistry, 10 Building 8, Pogodinskaya Street, 119121 Moscow, Russia.

Widespread pathologies such as atherosclerosis, metabolic syndrome and cancer are associated with dysregulation of sterol biosynthesis and metabolism. Cholesterol modulates the signaling pathways of neoplastic transformation and tumor progression. Lanosterol 14-alpha demethylase (cytochrome P450(51), CYP51A1) catalyzes one of the key steps in cholesterol biosynthesis. Read More

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Identification of Novel Inhibitors of DNA Ligase (LigA).

Molecules 2021 Apr 25;26(9). Epub 2021 Apr 25.

School of Biological Sciences and Institute of Biological and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DY, UK.

Present in all organisms, DNA ligases catalyse the formation of a phosphodiester bond between a 3' hydroxyl and a 5' phosphate, a reaction that is essential for maintaining genome integrity during replication and repair. Eubacterial DNA ligases use NAD as a cofactor and possess low sequence and structural homology relative to eukaryotic DNA ligases which use ATP as a cofactor. These key differences enable specific targeting of bacterial DNA ligases as an antibacterial strategy. Read More

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Tight Junction Protein Claudin-12 Is Involved in Cell Migration during Metastasis.

Biomolecules 2021 Apr 25;11(5). Epub 2021 Apr 25.

Department of Developmental Biology, Plovdiv University "Paisii Hilendarski", 4000 Plovdiv, Bulgaria.

Claudins are important components of the tight junctions determining barrier properties, cell polarity, and paracellular permeability. Although many functions of claudins in cancer cells have not been elucidated, recent studies have shown that claudins play an important role in cell migration and metastasis. Loss of epithelial/endothelial integrity, disruption of tight junctions, and increased paracellular leakage are often observed during metastasis. Read More

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Inhibition of Glycolysis Suppresses Cell Proliferation and Tumor Progression In Vivo: Perspectives for Chronotherapy.

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

Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 842 15 Bratislava, Slovakia.

A high rate of glycolysis is considered a hallmark of tumor progression and is caused by overexpression of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). Therefore, we analyzed the possibility of inhibiting tumor and endothelial cell metabolism through the inhibition of PFKFB3 by a small molecule, ()-1-(pyridin-4-yl)-3-(quinolin-2-yl)prop-2-en-1-one (PFK15), as a promising therapy. The effects of PFK15 on cell proliferation and apoptosis were analyzed on human umbilical vein endothelial cells (HUVEC) and the human colorectal adenocarcinoma cell line DLD1 through cytotoxicity and proliferation assays, flow cytometry, and western blotting. Read More

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Dual Role for Astroglial Copper-Assisted Polyamine Metabolism during Intense Network Activity.

Biomolecules 2021 Apr 19;11(4). Epub 2021 Apr 19.

Functional Pharmacology Research Group, Research Centre for Natural Sciences, Institute of Organic Chemistry, H-1117 Budapest, Hungary.

Astrocytes serve essential roles in human brain function and diseases. Growing evidence indicates that astrocytes are central players of the feedback modulation of excitatory Glu signalling during epileptiform activity via Glu-GABA exchange. The underlying mechanism results in the increase of tonic inhibition by reverse operation of the astroglial GABA transporter, induced by Glu-Na symport. Read More

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Null Effect of Transcranial Static Magnetic Field Stimulation over the Dorsolateral Prefrontal Cortex on Behavioral Performance in a Go/NoGo Task.

Brain Sci 2021 Apr 11;11(4). Epub 2021 Apr 11.

Department of Sensorimotor Neuroscience, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.

The purpose of this pilot study was to investigate whether transcranial static magnetic field stimulation (tSMS), which can modulate cortical excitability, would influence inhibitory control function when applied over the dorsolateral prefrontal cortex (DLPFC). Young healthy adults ( = 8, mean age ± SD = 24.4 ± 4. Read More

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L-Carnitine Tartrate Downregulates the ACE2 Receptor and Limits SARS-CoV-2 Infection.

Nutrients 2021 Apr 14;13(4). Epub 2021 Apr 14.

Institut de Recherche Clinique de Montreal, Montreal, QC H2W1R7, Canada.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Read More

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Viscous Core Liposomes Increase siRNA Encapsulation and Provides Gene Inhibition When Slightly Positively Charged.

Pharmaceutics 2021 Apr 1;13(4). Epub 2021 Apr 1.

Unité des Technologies Chimiques et Biologiques Pour la Santé (UTCBS), CNRS, INSERM, Université de Paris, F-75006 Paris, France.

Since its discovery, evidence that siRNA was able to act as an RNA interference effector, led to its acceptation as a novel medicine. The siRNA approach is very effective, due to its catalytic mechanism, but still the limitations of its cellular delivery should be addressed. One promising form of non-viral gene delivery system is liposomes. Read More

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Promising phytochemicals of traditional Himalayan medicinal plants against putative replication and transmission targets of SARS-CoV-2 by computational investigation.

Comput Biol Med 2021 Apr 20;133:104383. Epub 2021 Apr 20.

Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, 570 020, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India. Electronic address:

Background: Identification and repurposing of therapeutic and preventive strategies against COVID-19 are rapidly undergoing. Several medicinal plants from the Himalayan region have been traditionally used to treat various human disorders. Thus, in our current study, we intended to explore the potential ability of Himalayan medicinal plant (HMP) bioactives against COVID-19 using computational investigations. Read More

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Gluconeogenesis is reduced from alanine, lactate and pyruvate, but maintained from glycerol, in liver perfusion of rats with early and late sepsis.

Cell Biochem Funct 2021 Apr 29. Epub 2021 Apr 29.

Department of Physiological Sciences, State University of Londrina, Londrina, Brazil.

Sepsis induces several metabolic abnormalities, including hypoglycaemia in the most advanced stage of the disease, a risk factor for complications and death. Although hypoglycaemia can be caused by inhibition of hepatic gluconeogenesis, decreased and increased gluconeogenesis were reported in sepsis. Furthermore, gluconeogenesis from glycerol was not yet evaluated in this disease. Read More

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Inhibition of SARS-CoV-2 3CL M by Natural and Synthetic Inhibitors: Potential Implication for Vaccine Production Against COVID-19.

Front Mol Biosci 2021 12;8:640819. Epub 2021 Apr 12.

Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.

COVID-19 has created a pandemic situation all over the world. It has spread in nearly every continent. Researchers all over the world are trying to produce an effective vaccine against this virus, however; no specific treatment for COVID-19 has been discovered -so far. Read More

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PHMB-loaded PDMS and its antimicrobial properties for biomedical applications.

J Biomater Appl 2021 Apr 28:8853282211011921. Epub 2021 Apr 28.

Laboratory of Polymers, Center for Exact Sciences and Technology, University of Caxias do Sul, Rio Grande do Sul, Brazil.

Given the global panorama of demands in the health area, the development of biomaterials becomes irreducible for the maintenance and/or improvement in the quality of life of the human being. Aiming to reduce the impacts related to infections in the healing processes of the dermal structure, the present work proposes the development of polydimethylsiloxane (PDMS) based membranes with the incorporated polyhexamethylenebiguanide (PHMB) antimicrobial agent. In the present study, the antimicrobial and antibiofilm properties of polydimethylsiloxane (PDMS) films incorporated with 0. Read More

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The role of NHE3 (Slc9a3) in oxalate and sodium transport by mouse intestine and regulation by cAMP.

Physiol Rep 2021 Apr;9(7):e14828

Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.

Intestinal oxalate transport involves Cl /HCO exchangers but how this transport is regulated is not currently known. NHE3 (Slc9a3), an apical Na /H exchanger, is an established target for regulation of electroneutral NaCl absorption working in concert with Cl /HCO exchangers. To test whether NHE3 could be involved in regulation of intestinal oxalate transport and renal oxalate handling we compared urinary oxalate excretion rates and intestinal transepithelial fluxes of C-oxalate and Na between NHE3 KO and wild-type (WT) mice. Read More

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