1,248,956 results match your criteria inhibitors


Georgian Med News 2021 Mar(312):125-132

Tbilisi State Medical University, Departments of Pharmaceutical Technology and Medical Pharmacology, Georgia.

In the present article is considered antihypertensive and cardioprotective action of epoxieicosatrienoic acids (EETs) analogues and soluble epoxide hydrolase (sEH) inhibitors. Being epoxygenase products of arachidonic acid metabolism EETs provide a wide spectrum of biological activity in different organs implicated in the regulation of arterial pressure, including vascular endothelium (VE), heart and kidney. EETs are acting as autocrine or paracrine agents producing vasodilation, reduction in salt and fluid retention. Read More

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Georgian Med News 2021 Mar(312):7-14

Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of Health of the Russian Federation.

The aim of the study was to study the effectiveness of complex treatment of decompensated chronic venous insufficiency (CVI) using innovative techniques and proteolysis inhibitors with a wide spectrum of activity in patients with SARS-CoV-2 (COVID-19) in COVID hospital. This study was performed in the surgical department of COVID hospital on the basis of the Clinical Hospital No. 4 of the First Moscow State Medical University named I. Read More

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APE1 facilitates PD-L1-mediated progression of laryngeal and hypopharyngeal squamous cell carcinoma.

Int Immunopharmacol 2021 May 6;97:107675. Epub 2021 May 6.

Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China. Electronic address:

Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HSCC) seriously affect the life quality of patients. Nowadays, immunotherapy is widely used in the treatment of cancer. Tumor-infiltrating lymphocytes (TILs), programmed cell death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) play key roles in the immunotherapy of cancer. Read More

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New nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold: Design, synthesis, in silico and in vitro studies.

Biomed Pharmacother 2021 May 6;139:111678. Epub 2021 May 6.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy of Iași, 16 University Street, Iasi, Romania. Electronic address:

In this study we present design and synthesis of nineteen new nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold (NO-IND-TZDs) (6a-s), as a new safer and efficient multi-targets strategy for inflammatory diseases. The chemical structure of all synthesized derivatives (intermediaries and finals) was proved by NMR and mass spectroscopic analysis. In order to study the selectivity of NO-IND-TZDs for COX isoenzymes (COX-1 and COX-2) a molecular docking study was performed using AutoDock 4. Read More

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Targeting the transcription cycle and RNA processing in cancer treatment.

Curr Opin Pharmacol 2021 May 5;58:69-75. Epub 2021 May 5.

Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA, USA; Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

The transcriptional program and RNA splicing machinery are highly and frequently dysregulated in human cancers due to genomic and epigenomic alterations during tumorigenesis. This leads to cancer-specific dependencies on components of the transcriptional program and RNA splicing machinery, providing alternative and targetable 'Achilles' heels' for cancer treatment in the clinic. To target these vulnerabilities in cancer cells, potent and specific transcriptional CDK inhibitors and chemical compounds that impair splicing have been developed and evaluated in preclinical cancer models. Read More

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Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents.

Eur J Med Chem 2021 Apr 28;221:113480. Epub 2021 Apr 28.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan, 250012, China. Electronic address:

With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. Read More

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Efficient conversion of hemicellulose sugars from spent sulfite liquor into optically pure L-lactic acid by Enterococcus mundtii.

Bioresour Technol 2021 Apr 27;333:125215. Epub 2021 Apr 27.

Institute of Microbiology and Microbial Biotechnology, Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, 1190 Vienna, Austria. Electronic address:

Spent sulfite liquor (SSL), a waste stream from wood pulp production, has great potential as carbon source for future industrial fermentations. In the present study, SSL was separated into a hemicellulose derived sugar syrup (HDSS) and a lignosulfonic fraction by simulated moving bed chromatography. The recovery of SSL sugars in the HDSS was 89% and the fermentation inhibitors furfural, 5-hydroxymethylfurfural and acetic acid were removed by 98. Read More

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Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents.

Bioorg Chem 2021 Apr 27;112:104947. Epub 2021 Apr 27.

Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Riyadh, Saudi Arabia; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt. Electronic address:

Vascular endothelial growth factor-2 (VEGFR-2) is considered one of the most important factors in tumor angiogenesis, and consequently a number of anticancer therapeutics have been developed to inhibit VEGFR-2 signaling. Accordingly, eighteen derivatives of thieno[2,3-d]pyrimidines having structural characteristics similar to VEGFR-2 inhibitors were designed and synthesized. Anticancer activities of the new derivatives were assessed against three human cancer cell lines (HCT-116, HepG2, and MCF-7) using MTT. Read More

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Enantiomeric profiling of a chiral benzothiazole necroptosis inhibitor.

Bioorg Med Chem Lett 2021 May 5:128084. Epub 2021 May 5.

School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address:

Necroptosis is a form of programmed cell death that contributes to the pathophysiology of multiple diseases. Development of small-molecule anti-necroptosis agents has great promising clinical therapeutic relevance. The benzothiazole compounds were discovered by our group from an in-house fluorine-containing compound library as potent necroptosis inhibitors. Read More

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Immunotherapy as Single Treatment for Non-small-cell Lung Cancer Patients with Brain Metastases: a systematic review and meta-analysis - the META-L-BRAIN study.

J Thorac Oncol 2021 May 5. Epub 2021 May 5.

AC Camargo Cancer Center, São Paulo, Brazil.

Introduction: Brain metastases (BM) occur in 40% of lung cancer patients. The activity of immunotherapy in these patients, however, remains controversial, as the cornerstone treatment is radiotherapy (RT). Since RT is associated with adverse events that may impair quality of life, the possibility of substituting it by a single systemic approach is attractive. Read More

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Cocktail strategy for 'cold' tumors therapy via active recruitment of CD8+ T cells and enhancing their function.

J Control Release 2021 May 5. Epub 2021 May 5.

College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, PR China. Electronic address:

In immunotherapy, 'cold' tumors, with low T cells infiltration, hardly benefit from the treatment of immune checkpoint inhibitors (ICIs). To address this issue, we screened two 'cold' tumor models for mice with high expression of galectin-3 (Gal-3) and designed a cocktail strategy to actively recruit CD8+ T cells into the tumor microenvironment (TME), which reversed 'cold' tumors into 'hot' and remarkably elevated their ICIs-responsiveness. Gal-3, an important driving force of tumorigenesis, inhibits T cell infiltration into tumor tissue that shapes 'cold' tumor phenotype, and promotes tumor metastasis. Read More

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A Comprehensive Review on Pharmacology of Efflux Pumps and their Inhibitors in Antibiotic Resistance.

Eur J Pharmacol 2021 May 5:174151. Epub 2021 May 5.

Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, UP, India. Electronic address:

The potential for the build-up of resistance to a particular antibiotic endangers its therapeutic application over time. In recent decades, antibiotic resistance has become one of the most severe threats to public health. It can be attributed to the relentless and unchecked use of antibiotics in healthcare sectors, cell culture, animal husbandry, and agriculture. Read More

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Randialic acid B and tomentosolic acid block formyl peptide receptor 1 in human neutrophils and attenuate psoriasis-like inflammation in vivo.

Biochem Pharmacol 2021 May 5:114596. Epub 2021 May 5.

Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan. Electronic address:

Psoriasis is a long-lasting inflammatory skin disease lacking proper cure. Dysregulated activation of neutrophils is a major pathogenic factor in psoriasis. Formyl peptide receptor 1 (FPR1) triggers neutrophil activation in response to bacteria- or mitochondria-derived N-formyl peptides, but its significance in neutrophilic psoriasis remains unknown. Read More

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Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma.

Biochem Pharmacol 2021 May 5:114593. Epub 2021 May 5.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Research Center of Chinese Herbal Resources Science and Engineering, School of Pharmaceutical Sciences, Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address:

Aberrant activation of the Hedgehog (Hh) pathway is implicated in the pathogenesis and development of multiple cancers, especially Hh-driven medulloblastoma (MB). Smoothened (SMO) is a promising therapeutic target of the Hh pathway in clinical cancer treatment. However, SMO mutations frequently occur, which leads to drug resistance and tumor relapse. Read More

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Proteases inhibitors-insensitive cysteine proteases allow Nezara viridula to feed on growing seeds of field-grown soybean.

J Insect Physiol 2021 May 5:104250. Epub 2021 May 5.

Universidad de Buenos Aires, Facultad de Agronomía, Cátedra de Bioquímica, Buenos Aires, Argentina; Instituto de Investigaciones en Biociencias Agrícolas y Ambientales (INBA-CONICET), Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, (CONICET), Buenos Aires, Argentina. Electronic address:

The southern green stink bug, Nezara viridula is one of the primary soybean pests and causes significant economic losses around the world. In spite of the high proteases inhibitor (PI) levels, N. viridula can feed on developing seeds of field-grown soybean and reduce crop yields. Read More

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Monitoring of diverse enteric pathogens across environmental and host reservoirs with TaqMan array cards and standard qPCR: a methodological comparison study.

Lancet Planet Health 2021 May;5(5):e297-e308

Department of Civil Engineering, Monash University, Clayton, VIC, Australia. Electronic address:

Background: Multiple bacteria, viruses, protists, and helminths cause enteric infections that greatly impact human health and wellbeing. These enteropathogens are transmited via several pathways through human, animal, and environmental reservoirs. Individual qPCR assays have been extensively used to detect enteropathogens within these types of samples, whereas the TaqMan array card (TAC), which allows simultaneous detection of multiple enteropathogens, has only previously been validated in human clinical samples. Read More

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Specific inhibition of oncogenic RAS using cell-permeable RAS-binding domains.

Cell Chem Biol 2021 May 4. Epub 2021 May 4.

United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1193, Japan. Electronic address:

Oncogenic RAS proteins, common oncogenic drivers in many human cancers, have been refractory to conventional small-molecule and macromolecule inhibitors due to their intracellular localization and the lack of druggable pockets. Here, we present a feasible strategy for designing RAS inhibitors that involves intracellular delivery of RAS-binding domain (RBD), a nanomolar-affinity specific ligand of RAS. Screening of 51 different combinations of RBD and cell-permeable peptides has identified Pen-cRaf-v1 as a cell-permeable pan-RAS inhibitor capable of targeting both G12C and non-G12C RAS mutants. Read More

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Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis.

Cell 2021 Apr 30. Epub 2021 Apr 30.

Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA; Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA; Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, IL 60637, USA; University of Chicago Comprehensive Cancer Center, The University of Chicago, Chicago, IL 60637, USA; Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA. Electronic address:

Cancer cell genetic variability and similarity to host cells have stymied development of broad anti-cancer therapeutics. Our innate immune system evolved to clear genetically diverse pathogens and limit host toxicity; however, whether/how innate immunity can produce similar effects in cancer is unknown. Here, we show that human, but not murine, neutrophils release catalytically active neutrophil elastase (ELANE) to kill many cancer cell types while sparing non-cancer cells. Read More

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Retinoic acid stimulates transcription of the rat SHARP-2 gene via multiple pathways.

J Biochem 2021 May 8. Epub 2021 May 8.

Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan.

Members of the enhancer of split- and hairy-related protein (SHARP) family, SHARP-1 and SHARP-2, are basic helix-loop-helix transcriptional repressors and belong to the clock genes. In this study, an effect of retinoic acid (RA) on the SHARP family gene expression in the differentiated cells was examined. RA rapidly and temporarily induced the SHARP-2 mRNA expression in hepatic H4IIE cells. Read More

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Pharmacological SARM1 inhibition protects axon structure and function in paclitaxel-induced peripheral neuropathy.

Brain 2021 May 8. Epub 2021 May 8.

Disarm Therapeutics, a wholly owned subsidiary of Eli Lilly & Co., Cambridge MA 02142, USA.

Axonal degeneration is an early and ongoing event that causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems. Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of morbidity and the main cause of dose reductions and discontinuations in cancer treatment. Preclinical evidence indicates that activation of the Wallerian-like degeneration pathway driven by SARM1 is responsible for axonopathy in CIPN. Read More

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SGLT2 Inhibitors in Cardiovascular Medicine.

Eur Heart J Cardiovasc Pharmacother 2021 May 8. Epub 2021 May 8.

Department of Medicine, Einstein-Mount Sinai Diabetes Research Center (ES-DRC), Fleischer Institute for Diabetes and Metabolism (FIDAM), Albert Einstein College of Medicine, New York, NY, 10461, USA.

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Medulloblastoma recurrence and metastatic spread are independent of colony-stimulating factor 1 receptor signaling and macrophage survival.

J Neurooncol 2021 May 8. Epub 2021 May 8.

Division of Hematology/Oncology, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

Purpose: Tumor infiltration by immunosuppressive myeloid cells or tumor-associated macrophages (TAMs) contributes to tumor progression and metastasis. In contrast to their adult counterparts, higher TAM signatures do not correlate with aggressive tumor behavior in pediatric brain tumors. While prominent TAM infiltrates exist before and after radiation, the degree to which irradiated macrophages and microglia support progression or leptomeningeal metastasis remains unclear. Read More

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Effect of epigallocatechin-3-gallate and thermal cycling on the bond strength of resin cements to the root dentin.

Odontology 2021 May 8. Epub 2021 May 8.

School of Dentistry, University of Ribeirão Preto, Avenida Costábile Romano, 2201-Ribeirânia, Ribeirão Prêto, Sao Paulo, 14096-000, Brazil.

This study evaluated the effect of epigallocatechin-3-gallate (EGCG) solution and thermal cycling on the bond strength (BS) of fiber posts to the root dentin using two different resin cements (conventional or self-adhesive). One hundred and forty-four bovine roots were endodontically treated. After post space preparation, specimens were randomly divided into six groups (n = 24) according to dentin pretreatment [distilled water, 0. Read More

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Prognostic value and characterization of NTRK1 variation by fluorescence in situ hybridization in esophageal squamous cell carcinoma.

J Cancer Res Clin Oncol 2021 May 8. Epub 2021 May 8.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.

Purpose: Rearrangement of the neurotrophic tyrosine kinase receptor (NTRK) 1 gene is a target of tropomyosin receptor kinase A (TRKA) inhibitors, and its targeted drug (larotrectinib) has been approved by the US Food and Drug Administration. We investigated the existence and prognostic importance of NTRK1 variation in esophageal squamous cell carcinoma (ESCC).

Methods: Fluorescence in situ hybridization of a NTRK1 rearrangement was conducted on 523 ESCC samples through tissue microarrays. Read More

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StackIL6: a stacking ensemble model for improving the prediction of IL-6 inducing peptides.

Brief Bioinform 2021 May 8. Epub 2021 May 8.

Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand.

The release of interleukin (IL)-6 is stimulated by antigenic peptides from pathogens as well as by immune cells for activating aggressive inflammation. IL-6 inducing peptides are derived from pathogens and can be used as diagnostic biomarkers for predicting various stages of disease severity as well as being used as IL-6 inhibitors for the suppression of aggressive multi-signaling immune responses. Thus, the accurate identification of IL-6 inducing peptides is of great importance for investigating their mechanism of action as well as for developing diagnostic and immunotherapeutic applications. Read More

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3D Interrelationship between Osteocyte Network and Forming Mineral during Human Bone Remodeling.

Adv Healthc Mater 2021 May 8:e2100113. Epub 2021 May 8.

Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, 14476, Germany.

During bone remodeling, osteoblasts are known to deposit unmineralized collagenous tissue (osteoid), which mineralizes after some time lag. Some of the osteoblasts differentiate into osteocytes, forming a cell network within the lacunocanalicular network (LCN) of bone. To get more insight into the potential role of osteocytes in the mineralization process of osteoid, sites of bone formation are three-dimensionally imaged in nine forming human osteons using focused ion beam-scanning electron microscopy (FIB-SEM). Read More

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TRAIL-Armed ER Nanosomes Induce Drastically Enhanced Apoptosis in Resistant Tumor in Combination with the Antagonist of IAPs (AZD5582).

Adv Healthc Mater 2021 May 8:e2100030. Epub 2021 May 8.

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 51006, China.

Although mesenchymal stem cells (MSCs) can be engineered to deliver the TNF-related apoptosis-inducing ligand (TRAIL) as an effective anticancer therapy, the clinical application is hampered by the costly manufacturing of therapeutic MSCs. Therefore, it is needed to find an alternative cell-free therapy. In this study, TRAIL-armed endoplasmic reticulum (ER)-derived nanosomes (ERN-T) are successfully prepared with an average size of 70. Read More

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[Salvianolic acid B and its magnesium salt inhibit SARS-CoV-2 infection of Vero-E6 cells by blocking spike protein-mediated membrane fusion].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Apr;41(4):475-482

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

Objective: The investigate the inhibitory effects of the traditional Chinese medicine (TCM) monomer salvianolic acid B (Sal-B) and its magnesium salt Salvia Miltiorrhiza Polyphenolate Injection (ZDDY) against SARS-CoV-2 infection and explore the molecular mechanism.

Objective: The anti-SARS-CoV-2 activity of Sal-B and ZDDY was assessed using the authentic and pseudotyped SARS-CoV-2 infection assay. The antiviral targets of Sal-B were identified by molecular docking and molecular dynamics simulation. Read More

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Post-Liver Transplant Acute Kidney Injury.

Liver Transpl 2021 May 8. Epub 2021 May 8.

Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada.

Acute kidney injury (AKI) is a common condition following liver transplantation (LT). It negatively impacts patient outcomes by increasing the chances of developing chronic kidney disease (CKD) and reducing graft and patient survival. Multiple definitions of AKI have been proposed and utilized throughout the years with the International Club of Ascites (ICA) definition being the most widely used now for cirrhosis patients. Read More

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Discovery of Novel SecA Inhibitors against 'Candidatus Liberibacter asiaticus' through Virtual Screening and Biological Evaluation.

Chem Biol Drug Des 2021 May 8. Epub 2021 May 8.

Zhejiang Yangshengtang Institute of Natural Medication co. LTD, Hangzhou, 310024, China.

'Candidatus Liberibacter asiaticus' (Ca. L. asiaticus) is the causal agent of Huanglongbing (HLB) disease of citrus and current study focuses on the discovery of novel small-molecule inhibitors against SecA protein of Ca. Read More

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