4,503 results match your criteria inhibited altering


Ganglioside Alters Phospholipase Trafficking, Inhibits NF-κB Assembly, and Protects Tight Junction Integrity.

Front Nutr 2021 5;8:705172. Epub 2021 Jul 5.

Agricultural, Food & Nutritional Science, University of Alberta, Edmonton, AB, Canada.

Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. Read More

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Mutants of human ACE2 differentially promote SARS-CoV and SARS-CoV-2 spike mediated infection.

PLoS Pathog 2021 07 16;17(7):e1009715. Epub 2021 Jul 16.

Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.

SARS-CoV and SARS-CoV-2 encode spike proteins that bind human ACE2 on the cell surface to enter target cells during infection. A small fraction of humans encode variants of ACE2, thus altering the biochemical properties at the protein interaction interface. These and other ACE2 coding mutants can reveal how the spike proteins of each virus may differentially engage the ACE2 protein surface during infection. Read More

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The dual distinct role of telomerase in repression of senescence and myofibroblast differentiation.

Aging (Albany NY) 2021 07 12;13(13):16957-16973. Epub 2021 Jul 12.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Many aging related diseases such as cancer implicate the myofibroblast in disease progression. Furthermore genesis of the myofibroblast is associated with manifestation of cellular senescence of unclear significance. In this study we investigated the role of a common regulator, namely telomerase reverse transcriptase (TERT), in order to evaluate the potential significance of this association between both processes. Read More

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The BRD4 inhibitor JQ1 promotes melanoma cell apoptosis by regulating mitochondrial dynamics.

Cancer Sci 2021 Jul 12. Epub 2021 Jul 12.

Department of Otorhinolaryngology-Head and Neck Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.

Although the role of bromodomain-containing protein 4 (BRD4) in ovarian cancer, pancreatic cancer, multiple lymphoma and many other diseases is well known, its function in cutaneous melanoma is only partially understood. Here, our results show that the BRD4 inhibitor JQ1 promotes the apoptosis of B16 melanoma cells by altering mitochondrial dynamics, thereby inducing mitochondrial dysfunction and increasing oxidative stress. We found that treatment of B16 cells with different concentrations of JQ1 (125 nM or 250 nM), significantly downregulated the expression of protein subunits involved in mitochondrial respiratory chain complexes I, III, IV, and V, increased reactive oxygen species (ROS), induced energy metabolism dysfunction, significantly enhanced apoptosis and activated the mitochondrial apoptosis pathway. Read More

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C-C chemokine receptor type 6 modulates the biological function of osteoblastogenesis by altering the expression levels of Osterix and OPG/RANKL.

Biosci Trends 2021 Jul 11. Epub 2021 Jul 11.

Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Circulating inflammatory factors affect osteoblast and osteoclast formation and activity in osteoporosis. Estrogen affects the migration of Th17 cells via the C-C chemokine receptor type 6 (CCR6) and C-C chemokine ligand 20 (CCL20) signaling pathways to modulate bone metabolism; however, it is unclear whether and how CCR6 modulates bone homeostasis. In the present study, CCR6 knockout (CCR6) mice were selected to investigate the effects of CCR6 in the regulation of homeostasis of osteoblasts and osteoclasts. Read More

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Endothelial cell-derived Apelin inhibits tumor growth by altering immune cell localization.

Sci Rep 2021 Jul 7;11(1):14047. Epub 2021 Jul 7.

Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, 565-0871, Japan.

The Apelin/APJ signalling pathway, involved in multiple physiological and pathological processes, has been attracting increasing interest recently. In our previous study, Apelin overexpression in colon26 tumor cells suppressed tumor growth by inducing vascular maturation. Here, we found that MC38 and LLC tumor growth were greater in the absence of Apelin than in wild-type (WT) mice, suggesting that Apelin acts as a tumor suppressor. Read More

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Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines.

Neuron 2021 Jun 26. Epub 2021 Jun 26.

Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China. Electronic address:

Early-life inflammation increases the risk for depression in later life. Here, we demonstrate how early-life inflammation causes adolescent depressive-like symptoms: by altering the long-term neuronal spine engulfment capacity of microglia. For mice exposed to lipopolysaccharide (LPS)-induced inflammation via the Toll-like receptor 4/NF-κB signaling pathway at postnatal day (P) 14, ongoing longitudinal imaging of the living brain revealed that later stress (delivered during adolescence on P45) increases the extent of microglial engulfment around anterior cingulate cortex (ACC) glutamatergic neuronal (ACC) spines. Read More

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High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats.

Ecotoxicol Environ Saf 2021 Jul 2;222:112461. Epub 2021 Jul 2.

Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address:

This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Read More

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ZEB1 represses biogenesis of circ-DOCK5 to facilitate metastasis in esophageal squamous cell carcinoma via a positive feedback loop with TGF-β.

Cancer Lett 2021 Jun 30;519:117-129. Epub 2021 Jun 30.

Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, People's Republic of China; Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, People's Republic of China. Electronic address:

ZEB1 is an important transcription factor that plays a critical role in TGF-β-induced epithelial-mesenchymal transition (EMT) and tumor metastasis. However, the mechanisms by which ZEB1 regulates metastasis in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here, we identified a novel circular RNA, circ-DOCK5, the biogenesis of which is directly regulated by ZEB1 and ZEB1-repressed RNA-binding protein eIF4A3. Read More

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Eritoran Attenuates Hepatic Inflammation and Fibrosis in Mice with Chronic Liver Injury.

Cells 2021 Jun 21;10(6). Epub 2021 Jun 21.

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Toll-like receptor 4 (TLR4) signaling plays a key role in liver inflammation and fibrosis. The therapeutic effects of eritoran, a TLR4 antagonist, in mice with chronic liver injury remained unclear. C57BL/6 mice were fed a fast-food diet (FFD) or treated with carbon tetrachloride (CCl) to induce chronic liver injury. Read More

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Effects of Nocturnal UV-B Irradiation on Growth, Flowering, and Phytochemical Concentration in Leaves of Greenhouse-Grown Red Perilla.

Plants (Basel) 2021 Jun 20;10(6). Epub 2021 Jun 20.

Graduate School of Horticulture, Chiba University, Matsudo 648, Matsudo, Chiba 271-8510, Japan.

In Japan, red perilla leaves are used in the food and coloring industries, as well as in crude medicine. Perilla leaves contain a high concentration of phytochemicals such as perillaldehyde (PA) and rosmarinic acid (RA). The effects of UV-B radiation intensity (0. Read More

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Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of Nsp5 main protease.

Biochem J 2021 07;478(13):2499-2515

Chromosome Replication Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, U.K.

The coronavirus 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread around the world with unprecedented health and socio-economic effects for the global population. While different vaccines are now being made available, very few antiviral drugs have been approved. The main viral protease (nsp5) of SARS-CoV-2 provides an excellent target for antivirals, due to its essential and conserved function in the viral replication cycle. Read More

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Antiadhesion and antibiofilm potential of Fagonia indica from Cholistan desert against clinical multidrug resistant bacteria.

Braz J Biol 2021 28;82:e239991. Epub 2021 Jun 28.

Government College University, Department of Microbiology, Faisalabad, Pakistan.

High resistance to antimicrobials is associated with biofilm formation responsible for infectious microbes to withstand severe conditions. Therefore, new alternatives are necessary as biofilm inhibitors to control infections. In this study, the antimicrobial and antibiofilm activities of Fagonia indica extracts were evaluated against MDR clinical isolates. Read More

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Enterococcus faecium PNC01 isolated from the intestinal mucosa of chicken as an alternative for antibiotics to reduce feed conversion rate in broiler chickens.

Microb Cell Fact 2021 Jun 28;20(1):122. Epub 2021 Jun 28.

State Key Laboratory of Animal Nutrition, Department of Animal Nutrition & Feed Science, College of Animal Science & Technology, China Agricultural University, Haidian District, Beijing, 100193, China.

Background: The development and utilization of probiotics had many environmental benefits for replacing antibiotics in animal production. Bacteria in the intestinal mucosa have better adhesion to the host intestinal epithelial cells compared to bacteria in the intestinal contents. In this study, lactic acid bacteria were isolated from the intestinal mucosa of broiler chickens and investigated as the substitution to antibiotic in broiler production. Read More

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Traditional Chinese Medicine Xihuang Wan Inhibited Lewis Lung Carcinoma in a Syngeneic Model, Equivalent to Cytotoxic Chemotherapy, by Altering Multiple Signaling Pathways.

In Vivo 2021 Jul-Aug;35(4):2005-2014

Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, P.R. China;

Background/aim: Xihuang Wan (XHW), a traditional Chinese medicine (TCM), has been used in China for a variety of cancers including lung cancer. The present study evaluated the efficacy of XHW on a Lewis lung mouse model and explored the potential mechanism via transcriptomics.

Materials And Methods: The mice were randomized into 6 groups: 1) untreated control (n=10); 2) low-dose XHW; 3) medium-dose XHW; 4) high-dose XHW; 5) cisplatin; and 6) untreated blank (n=4). Read More

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Deubiquitination of MITF-M Regulates Melanocytes Proliferation and Apoptosis.

Front Mol Biosci 2021 9;8:692724. Epub 2021 Jun 9.

College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

Microphthalmia-associated transcription factor-M (MITF-M) is the key gene in the proliferation and differentiation of melanocytes, which undergoes an array of post-translation modifications. As shown in our previous study, deubiquitinase USP13 is directly involved in melanogenesis. However, it is still ambiguous that the effect of USP13-mediated MITF-M expression on melanocytes proliferation and apoptosis. Read More

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Removing chlorinated haloacetaldehydes from drinking water by household heating devices with and without chlorine: Efficiency, influencing factors, and mechanisms.

Chemosphere 2021 Jun 15;284:131202. Epub 2021 Jun 15.

Key Laboratory of Microorganism Application and Risk Control of Shenzhen, Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental Safety, Institute of Environment and Ecology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, 518055, China.

Haloacetaldehyde (HAL) is a type of disinfection byproduct (DBP) commonly detected in disinfected drinking water, and concerns toward its cytotoxic effects have promoted numerous efforts to control it. Given that household water treatment (HWT) process is a promising approach to polish drinking water quality and has been widely used by public, we herein evaluated the performances of two household heating devices (electric kettle and microwave oven) on the removals of three types of chlorinated haloacetaldehydes (Cl-HALs) under varying operating and water conditions. Results showed that the removals of HALs by boiling water to 100 °C were not very efficient (<20%) under automatic switch-off mode when chlorine was absent. Read More

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Pharmacologic modulation of RNA splicing enhances anti-tumor immunity.

Cell 2021 Jul 24;184(15):4032-4047.e31. Epub 2021 Jun 24.

Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USA.

Although mutations in DNA are the best-studied source of neoantigens that determine response to immune checkpoint blockade, alterations in RNA splicing within cancer cells could similarly result in neoepitope production. However, the endogenous antigenicity and clinical potential of such splicing-derived epitopes have not been tested. Here, we demonstrate that pharmacologic modulation of splicing via specific drug classes generates bona fide neoantigens and elicits anti-tumor immunity, augmenting checkpoint immunotherapy. Read More

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Overexpression of Wilms tumor 1 promotes IL-1β expression by upregulating histone acetylation in keratinocytes.

Int Immunopharmacol 2021 Jul 2;96:107793. Epub 2021 Jun 2.

Department of Dermatology, Hunan Key Laboratory of Medical Epigenomes, The Second Xiangya Hospital of Central South University, Changsha 410000, China.

Psoriasis is a common inflammatory skin disease. Infiltration of inflammatory cells and excessive proliferation of keratinocytes are the histopathological markers of psoriasis. The transcription factor Wilms Tumor 1 (WT1) is overexpressed in several tumor types, and plays an important part in the proliferation and apoptosis of cells. Read More

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Dexmedetomidine Ameliorates Postoperative Cognitive Dysfunction in Aged Mice.

Neurochem Res 2021 Sep 23;46(9):2415-2426. Epub 2021 Jun 23.

Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.

Neuroinflammation and oxidative stress coexist and interact in the progression of postoperative cognitive dysfunction (POCD) and other neurodegenerative disease. Mounting studies reveal that Dexmedetomidine (Dex) possesses anti-inflammatory and antioxidant properties. Nevertheless, whether Dex exerts neuroprotective effect on the cognitive sequelae of oxidative stress and inflammatory process remains unclear. Read More

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September 2021

MiR-150 suppressed cell viability, invasion and EMT via HMGA2 in oral squamous cell carcinoma.

Eur Rev Med Pharmacol Sci 2021 Jun;25(11):3981-3989

Department of Stomatology, Yantaishan Hospital, Yantai, China.

Objective: Oral squamous cell carcinoma (OSCC) accounts for 90% of head and neck cancers, and its 5-year overall survival is very poor. MiR-150 is usually downregulated and acts as tumor suppressor in multiple cancers. The aim of our study is to explore the functions of miR-150 in OSCC. Read More

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Basolateral Amygdala Regulates EEG Theta-activity During Rapid Eye Movement Sleep.

Neuroscience 2021 08 17;468:176-185. Epub 2021 Jun 17.

Sleep Research Laboratory, Center for Integrative Neuroscience and Inflammatory Diseases, Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA, USA. Electronic address:

Pharmacological and optogenetic studies have demonstrated that the basolateral amygdala (BLA) plays a pivotal role in regulating fear-conditioned changes in sleep, in particular, rapid eye movement sleep (REM). However, the linkage between BLA and REM regulation has been minimally examined. In this study, we optogenetically activated or inhibited BLA selectively during spontaneous REM, and determined the effects on REM amounts and on hippocampus regulated EEG-theta (θ) activity. Read More

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Molecularly Functionalized Electrodes for Efficient Electrochemical Water Remediation.

ChemSusChem 2021 Jun 18. Epub 2021 Jun 18.

Advanced Materials for Energy-Water Systems (AMEWS) Energy Frontier Research Center, Argonne National Laboratory, Lemont, IL, 60439, USA.

The development and investigation of materials that leverage unique interfacial effects on electronic structure and redox chemistry are likely to play an outstanding role in advanced technologies for wastewater treatment. Here, the use of surface functionalization of metal oxides with a Ru poly(pyridyl) complex was reported as a way to create hybrid assemblies with optimized electrochemical performance for water remediation, superior to those that could be achieved with the molecular catalyst or metal-oxide electrodes used individually. Mechanistic analysis demonstrated that the molecularly functionalized electrodes could suppress the formation of hydroxyl radicals (i. Read More

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The Ethyl Acetate Extract From Promotes Apoptosis of Gastric Cancer Cells Through Mitochondria Regulation by PHB.

Front Pharmacol 2021 28;12:635467. Epub 2021 May 28.

Nanjing University of Traditional Chinese Medicine, Nanjing, China.

To investigate the effect of ethyl acetate extract from (COE) on gastric cancer cell apoptosis and reveal its underlying molecular mechanism. In addition, it was aimed to stablish a theoretical basis for the clinical application of in the gastric cancer treatment. Western blot and RT-qPCR were used to detect mRNA and protein expression of PHB in gastric cancer and adjacent tissues. Read More

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Metabolic alterations mediated by STAT3 promotes drug persistence in CML.

Leukemia 2021 Jun 12. Epub 2021 Jun 12.

Department of Medicine, Division of Hematology/Oncology, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.

Leukemic stem cells (LSCs) can acquire non-mutational resistance following drug treatment leading to therapeutic failure and relapse. However, oncogene-independent mechanisms of drug persistence in LSCs are incompletely understood, which is the primary focus of this study. We integrated proteomics, transcriptomics, and metabolomics to determine the contribution of STAT3 in promoting metabolic changes in tyrosine kinase inhibitor (TKI) persistent chronic myeloid leukemia (CML) cells. Read More

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Q134R: Small chemical compound with NFAT inhibitory properties improves behavioral performance and synapse function in mouse models of amyloid pathology.

Aging Cell 2021 Jul 12;20(7):e13416. Epub 2021 Jun 12.

Sanders-Brown Center on Aging, University of Kentucky College of Medicine, Lexington, KY, USA.

Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer's disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. Read More

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ATP biphasically modulates LLPS of TDP-43 PLD by specifically binding arginine residues.

Commun Biol 2021 Jun 10;4(1):714. Epub 2021 Jun 10.

Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore.

Mysteriously neurons maintain ATP concentrations of ~3 mM but whether ATP modulates TDP-43 LLPS remains completely unexplored. Here we characterized the effect of ATP on LLPS of TDP-43 PLD and seven mutants by DIC and NMR. The results revealed: 1) ATP induces and subsequently dissolves LLPS of TDP-43 PLD by specifically binding Arg saturated at 1:100. Read More

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Effect of 1α,25-Dihydroxyvitamin D3 on the Radiation Response in Prostate Cancer: Association With IL-6 Signaling.

Front Oncol 2021 24;11:619365. Epub 2021 May 24.

College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Radiotherapy (RT) is the main treatment modality for prostate cancer (PCa). This study investigated the role of IL-6 in biological sequelae following irradiation and highlighted the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on the radiation response of PCa and its relationship with IL-6 signaling. Human and murine PCa cell lines were used to examine the response to irradiation and . Read More

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Functional and behavioral effects of de novo mutations in calcium-related genes in patients with bipolar disorder.

Hum Mol Genet 2021 Jun 7. Epub 2021 Jun 7.

Department of Psychiatry & Behavioral Science, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Bipolar disorder is a common mental illness occurring in approximately 1% of individuals and exhibits lifetime prevalence. Although genetic factors are known to contribute to this disorder, the genetic architecture has not yet been completely clarified. Our initial trio-based exome sequencing study of bipolar disorder showed enrichment of de novo, loss-of-function (LOF) or protein-altering mutations in a combined group with bipolar I and schizoaffective disorders, and the identified de novo mutations were enriched in calcium-related genes. Read More

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In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα.

Sci Rep 2021 Jun 3;11(1):11663. Epub 2021 Jun 3.

Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, Canada.

The interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. Read More

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