48,608 results match your criteria pharmacology profiling

Discovery of a cell-active SuTEx ligand of prostaglandin reductase 2.

Chembiochem 2021 Apr 16. Epub 2021 Apr 16.

University of Virginia, Chemistry and Pharmacology, McCormick Road, PO Box 400319, 22904-4319, United States, 22904-4319, Charlottesville, UNITED STATES.

Sulfonyl-triazoles have emerged as a new reactive group for covalent modification of tyrosine sites on proteins through sulfur-triazole exchange (SuTEx) chemistry. The extent to which this sulfur electrophile can be tuned for developing ligands with cellular activity remains largely underexplored. Here, we performed fragment-based ligand discovery in live cells to identify SuTEx compounds capable of liganding tyrosine sites on diverse protein targets. Read More

View Article and Full-Text PDF

Proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy: potential targets in calcium regulatory network.

Sci Rep 2021 Apr 15;11(1):8252. Epub 2021 Apr 15.

Department of Medical Physiology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca homeostasis. Read More

View Article and Full-Text PDF

Time-resolved proteomics profiling of the ciliary Hedgehog response.

J Cell Biol 2021 May;220(5)

Center of Human and Molecular Biology, Saarland University School of Medicine, Homburg, Germany.

The primary cilium is a signaling compartment that interprets Hedgehog signals through changes of its protein, lipid, and second messenger compositions. Here, we combine proximity labeling of cilia with quantitative mass spectrometry to unbiasedly profile the time-dependent alterations of the ciliary proteome in response to Hedgehog. This approach correctly identifies the three factors known to undergo Hedgehog-regulated ciliary redistribution and reveals two such additional proteins. Read More

View Article and Full-Text PDF

Long Noncoding RNAs and Their Therapeutic Promise in Diabetic Nephropathy.

Nephron 2021 Apr 14:1-11. Epub 2021 Apr 14.

Section of Nephrology, Division of Internal Medicine, The University of Texas at MD Anderson Cancer Center, Houston, Texas, USA.

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Read More

View Article and Full-Text PDF

Sex-based differences in the activation of peripheral blood monocytes in early Parkinson disease.

NPJ Parkinsons Dis 2021 Apr 13;7(1):36. Epub 2021 Apr 13.

Alabama Morris K. Udall Center of Excellence in Parkinson's Disease Research, University of Alabama at Birmingham, 1719 Sixth Ave. South, Birmingham, AL, USA.

Increasing evidence supports the role of brain and systemic inflammation in the etiology of Parkinson disease (PD). We used gene expression profiling to examine the activation state of peripheral blood monocytes in 18 patients with early, untreated PD and 16 healthy control (HC) subjects. Monocytes were isolated by negative selection, and gene expression studied by RNA-seq and gene set enrichment analysis. Read More

View Article and Full-Text PDF

Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer.

Nucleic Acids Res 2021 Apr 13. Epub 2021 Apr 13.

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.

Castration-resistant prostate cancer (CRPC) is a terminal disease and the molecular underpinnings of CRPC development need to be better understood in order to improve its treatment. Here, we report that a transcription factor Yin Yang 1 (YY1) is significantly overexpressed during prostate cancer progression. Functional and cistrome studies of YY1 uncover its roles in promoting prostate oncogenesis in vitro and in vivo, as well as sustaining tumor metabolism including the Warburg effect and mitochondria respiration. Read More

View Article and Full-Text PDF

Discovery and Pharmacological Evaluation of STEAP4 as a Novel Target for HER2 Overexpressing Breast Cancer.

Front Oncol 2021 26;11:608201. Epub 2021 Mar 26.

Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.

Breast cancer (BC) is a highly heterogeneous disease encompassing multiple subtypes with different molecular and histopathological features, disease prognosis, and therapeutic responses. Among these, the Triple Negative BC form (TNBC) is an aggressive subtype with poor prognosis and therapeutic outcome. With respect to HER2 overexpressing BC, although advanced targeted therapies have improved the survival of patients, disease relapse and metastasis remains a challenge for therapeutic efficacy. Read More

View Article and Full-Text PDF

Using Big Data to Develop a Clinical Decision Support System for Tinnitus Treatment.

Curr Top Behav Neurosci 2021 Apr 11. Epub 2021 Apr 11.

First Department of Otorhinolaryngology, Head and Neck Surgery, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece.

Tinnitus is a common symptom of a phantom sound perception with a considerable socioeconomic impact. Tinnitus pathophysiology is enigmatic and its significant heterogeneity reflects a wide spectrum of clinical manifestations, severity and annoyance among tinnitus sufferers. Although several interventions have been suggested, currently there is no universally accepted treatment. Read More

View Article and Full-Text PDF

Novel preclinical patient-derived lung cancer models reveal inhibition of HER3 and MTOR signaling as therapeutic strategies for NRG1 fusion-positive cancers.

J Thorac Oncol 2021 Apr 8. Epub 2021 Apr 8.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Introduction: NRG1 rearrangements produce chimeric ligands that subvert the ERBB pathway to drive tumorigenesis. A better understanding of the signaling networks that mediate transformation by NRG1 fusions is needed to inform effective therapeutic strategies. However, this has been hampered by a paucity of patient-derived disease models that faithfully recapitulate this molecularly defined cancer subset. Read More

View Article and Full-Text PDF

Development of new therapeutic options for the treatment of uveal melanoma.

FEBS J 2021 Apr 10. Epub 2021 Apr 10.

The University of Sydney, Sydney Pharmacy School, Faculty of Medicine and Health, Sydney, NSW, 2006, Australia.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Important cytogenetic and genetic risk factors for the development of UM include chromosome 3 monosomy, mutations in the guanine nucleotide-binding proteins GNAQ/GNA11, and loss of the BRACA1-associated protein 1 (BAP 1). Most primary UMs are treated conservatively with radiotherapy, but enucleation is necessary for large tumours. Read More

View Article and Full-Text PDF

Hexokinase 2 discerns a novel circulating tumor cell population associated with poor prognosis in lung cancer patients.

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

Institute for Systems Biology, Seattle, WA 98109;

Unlike other epithelial cancer types, circulating tumor cells (CTCs) are less frequently detected in the peripheral blood of non-small cell lung cancer (NSCLC) patients using epithelial marker-based detection approaches despite the aggressive nature of NSCLC. Here, we demonstrate hexokinase-2 (HK2) as a metabolic function-associated marker for the detection of CTCs. In 59 NSCLC patients bearing cytokeratin-positive (CK) primary tumors, HK2 enables resolving cytokeratin-negative (HK2/CK) CTCs as a prevalent population in about half of the peripheral blood samples with positive CTC counts. Read More

View Article and Full-Text PDF

In silico analysis of the potential mechanism of a preventive Chinese medicine formula on coronavirus disease 2019.

J Ethnopharmacol 2021 Apr 5;275:114098. Epub 2021 Apr 5.

Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, China; Hunan Engineering Technology Research Center for Medicinal and Functional Food, Hunan University of Chinese Medicine, Changsha, China; Key Laboratory of TCM Heart and Lung Syndrome Differentiation, Medicated Diet and Dietotherapy, Hunan University of Chinese Medicine, Changsha, China. Electronic address:

Ethnopharmacological Relevance: With the spread of Coronavirus Disease (2019) (COVID-19), combination with traditional Chinese medicine (TCM) has been widely used as a prevention and therapy strategy in China. Xin guan No.1 (XG-1) prescription is a preventive formula recommended by the Hunan Provincial Administration of TCM to prevent the pandemic of COVID-19. Read More

View Article and Full-Text PDF

Transcriptomic Analysis of Mouse Brain After Traumatic Brain Injury Reveals That the Angiotensin Receptor Blocker Candesartan Acts Through Novel Pathways.

Front Neurosci 2021 22;15:636259. Epub 2021 Mar 22.

Graduate Program in Neuroscience, Uniformed Services University of the Health Sciences, Bethesda, MD, United States.

Traumatic brain injury (TBI) results in complex pathological reactions, where the initial lesion is followed by secondary inflammation and edema. Our laboratory and others have reported that angiotensin receptor blockers (ARBs) have efficacy in improving recovery from traumatic brain injury in mice. Treatment of mice with a subhypotensive dose of the ARB candesartan results in improved functional recovery, and reduced pathology (lesion volume, inflammation and gliosis). Read More

View Article and Full-Text PDF

Discovery of potential Q-marker of traditional Chinese medicine based on plant metabolomics and network pharmacology: Periplocae Cortex as an example.

Phytomedicine 2021 May 2;85:153535. Epub 2021 Mar 2.

Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, and International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University, Guangzhou 510632, China. Electronic address:

Background: Quality control exerted great importance on the clinical application of drugs for ensuring effectiveness and safety. Due to chemical complexity, diversity among different producing areas and harvest seasons, as well as unintentionally mixed with non-medicinal parts, the current quality standards of traditional Chinese medicine (TCM) still faced challenges in evaluating the overall chemical consistency.

Purpose: We aimed to develop a new strategy to discover potential quality marker (Q-marker) of TCM by integrating plant metabolomics and network pharmacology, using Periplocae Cortex (GP, the dried root bark of Periploca sepium Bge. Read More

View Article and Full-Text PDF

circRNA expression profiling of colon tissue from mesalazine-treated mouse of inflammatory bowel disease reveals an important circRNA-miRNA-mRNA pathway.

Aging (Albany NY) 2021 Mar 26;13. Epub 2021 Mar 26.

Department of Anal-Rectal Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Mesalazine (5-aminosalicylic acid, 5-ASA) has been widely used to treat inflammatory bowel disease (IBD). However, it remains unclear about the underlying biological mechanisms of IBD pathogenesis and mesalazine treatment, which could be partially clarified by exploring the profiling of circular RNAs (circRNAs) using RNA-seq. A total of 15 mice (C57BL/6) were randomly assigned to three equally sized groups: control, dextran sulfate sodium (DSS, using DSS to induce IBD), and DSS+5-ASA (using mesalazine to treat IBD). Read More

View Article and Full-Text PDF

HPLC-ESI/MS Profiling, Phytoconstituents isolation and Evaluation of Renal Function, Oxidative Stress and Inflammation in Gentamicin-Induced Nephrotoxicity in Rats of Ficus spragueana Mildbr. & Burret.

Biomed Chromatogr 2021 Apr 5:e5135. Epub 2021 Apr 5.

Medicinal and Pharmaceutical Chemistry Department (Pharmacology Group), Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), Dokki, Giza, Egypt.

Ficus spragueana Mildbr. & Burret, (family Moraceae), was reported to have various biological activities. However, its activity in treatment of renal injury was not investigated yet. Read More

View Article and Full-Text PDF

Nilotinib Improves Bioenergetic Profiling in Brain Astroglia in the 3xTg Mouse Model of Alzheimer's Disease.

Aging Dis 2021 Apr 1;12(2):441-465. Epub 2021 Apr 1.

1Division of Neurodegenerative Disorders, St. Boniface Hospital Research, Winnipeg, MB, Canada.

Current treatments targeting amyloid beta in Alzheimer's disease (AD) have minimal efficacy, which results in a huge unmet medical need worldwide. Accumulating data suggest that brain mitochondrial dysfunction play a critical role in AD pathogenesis. Targeting cellular mechanisms associated with mitochondrial dysfunction in AD create a novel approach for drug development. Read More

View Article and Full-Text PDF

Identification and selectivity profiling of small-molecule degraders via multi-omics approaches.

Cell Chem Biol 2021 Mar 29. Epub 2021 Mar 29.

CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Electronic address:

The therapeutic modality of targeted protein degradation promises to overcome limitations of traditional pharmacology. Small-molecule degraders recruit disease-causing proteins to E3 ubiquitin ligases, prompting their ubiquitination and degradation by the proteasome. The discovery, mechanistic elucidation, and selectivity profiling of novel degraders are often conducted in cellular systems. Read More

View Article and Full-Text PDF

CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Pharmacology, University of California San Diego, La Jolla, CA 92093;

Early spliceosome assembly requires phosphorylation of U1-70K, a constituent of the U1 small nuclear ribonucleoprotein (snRNP), but it is unclear which sites are phosphorylated, and by what enzyme, and how such modification regulates function. By profiling the proteome, we found that the Cdc2-like kinase 1 (CLK1) phosphorylates Ser-226 in the C terminus of U1-70K. This releases U1-70K from subnuclear granules facilitating interaction with U1 snRNP and the serine-arginine (SR) protein SRSF1, critical steps in establishing the 5' splice site. Read More

View Article and Full-Text PDF

Acute MDPV Binge Paradigm on Mice Emotional Behavior and Glial Signature.

Pharmaceuticals (Basel) 2021 Mar 16;14(3). Epub 2021 Mar 16.

Institute of Pharmacology and Experimental Therapeutics/IBILI, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.

3,4-Methylenedioxypyrovalerone (MDPV), a widely available synthetic cathinone, is a popular substitute for classical controlled drugs of abuse, such as methamphetamine (METH). Although MDPV poses public health risks, its neuropharmacological profile remains poorly explored. This study aimed to provide evidence on that direction. Read More

View Article and Full-Text PDF

Towards Extending the Detection Window of Gamma-Hydroxybutyric Acid-An Untargeted Metabolomics Study in Serum and Urine Following Controlled Administration in Healthy Men.

Metabolites 2021 Mar 12;11(3). Epub 2021 Mar 12.

Department of Forensic Pharmacology & Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, 8057 Zurich, Switzerland.

In forensic toxicology, gamma-hydroxybutyrate (GHB) still represents one of the most challenging drugs of abuse in terms of analytical detection and interpretation. Given its rapid elimination, the detection window of GHB in common matrices is short (maximum 12 h in urine). Additionally, the differentiation from naturally occurring endogenous GHB, is challenging. Read More

View Article and Full-Text PDF

Ribosome-Profiling Reveals Restricted Post Transcriptional Expression of Antiviral Cytokines and Transcription Factors during SARS-CoV-2 Infection.

Int J Mol Sci 2021 Mar 25;22(7). Epub 2021 Mar 25.

CSIRO Health & Biosecurity, the Australian Centre for Disease Preparedness, Private Bag 24, Geelong 3220, Australia.

The global COVID-19 pandemic caused by SARS-CoV-2 has resulted in over 2.2 million deaths. Disease outcomes range from asymptomatic to severe with, so far, minimal genotypic change to the virus so understanding the host response is paramount. Read More

View Article and Full-Text PDF

Analysis of ADAM12-Mediated Ephrin-A1 Cleavage and Its Biological Functions.

Int J Mol Sci 2021 Mar 1;22(5). Epub 2021 Mar 1.

Department of Pharmacology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.

Accumulating evidence indicates that an elevated ephrin-A1 expression is positively correlated with a worse prognosis in some cancers such as colon and liver cancer. The detailed mechanism of an elevated ephrin-A1 expression in a worse prognosis still remains to be fully elucidated. We previously reported that ADAM12-cleaved ephrin-A1 enhanced lung vascular permeability and thereby induced lung metastasis. Read More

View Article and Full-Text PDF

Glyphosate and AMPA Induce Alterations in Expression of Genes Involved in Chromatin Architecture in Human Peripheral Blood Mononuclear Cells (In Vitro).

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.

We have determined the effect of glyphosate and aminomethylphosphonic acid (AMPA) on expression of genes involved in chromatin architecture in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with glyphosate and AMPA in the concentrations ranging from 0.5 to 100 μM and from 0. Read More

View Article and Full-Text PDF

Solitary Fibrous Tumor/Hemangiopericytoma Metastasizes Extracranially, Associated with Altered Expression of WNT5A and MMP9.

Cancers (Basel) 2021 Mar 7;13(5). Epub 2021 Mar 7.

Departments of Neurosurgery, Chonnam National University Research Institute of Medical Science, Chonnam National University Hwasun Hospital and Medical School, Hwasun 58128, Korea.

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is a mesenchymal tumor originating from various soft tissues and meninges, which carries the - fusion gene. Meningeal/intracranial SFT/HPCs (SFT/HPC) have a poor clinical outcome with metastatic behavior compared to soft tissue/extracranial SFT/HPCs (SFT/HPC), but the underlying genetic factors are unclear. Differentially expressed genes (DEGs) were analyzed by NanoString nCounter assay using RNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue samples. Read More

View Article and Full-Text PDF

Coupling Microplate-Based Antibacterial Assay with Liquid Chromatography for High-Resolution Growth Inhibition Profiling of Crude Extracts: Validation and Proof-of-Concept Study with .

Molecules 2021 Mar 11;26(6). Epub 2021 Mar 11.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

With the identification of novel antibiotics from nature being pivotal in the fight against human pathogenic bacteria, there is an urgent need for effective methodologies for expedited screening of crude extracts. Here we report the development and validation of a simple and dye-free antimicrobial assay in 96-well microplate format, for both determination of IC values and high-resolution inhibition profiling to allow pin-pointing of bioactive constituents directly from crude extracts. While commonly used antimicrobial assays visualize cell viability using dyes, the developed and validated assay conveniently uses OD measurements directly on the fermentation broth. Read More

View Article and Full-Text PDF

Molecular Profiling of Docetaxel-Resistant Prostate Cancer Cells Identifies Multiple Mechanisms of Therapeutic Resistance.

Cancers (Basel) 2021 Mar 14;13(6). Epub 2021 Mar 14.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.

Docetaxel-a taxane-based chemotherapeutic agent-was the first treatment to demonstrate significant improvements in overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, the response to docetaxel is generally short-lived, and relapse eventually occurs due to the development of resistance. To explore the mechanisms of acquired docetaxel resistance in prostate cancer (PCa) and set these in the context of androgen deprivation therapy, we established docetaxel-resistant PCa cell lines, derived from the androgen-dependent LNCaP cell line, and from the LNCaP lineage-derived androgen-independent C4-2B sub-line. Read More

View Article and Full-Text PDF

Network pharmacology to explore the anti-inflammatory mechanism of Xuebijing in the treatment of sepsis.

Phytomedicine 2021 May 17;85:153543. Epub 2021 Mar 17.

Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRist, Department of Automation, Tsinghua University, 100084 Beijing, China. Electronic address:

Background: Xuebijing (XBJ) is a traditional Chinese patent medicine for sepsis. However, the mechanism of action (MoA) of XBJ on sepsis remain unclear.

Purpose: Elucidate the MoA of XBJ for treating sepsis based on network pharmacology. Read More

View Article and Full-Text PDF

A transgenic pig model expressing a CMV-ZsGreen1 reporter across an extensive array of tissues.

J Biomed Res 2020 Dec;35(2):163-173

Department of Animal Science, University of Nebraska-Lincoln, Lincoln, NE 68583-0908, USA.

Since genetic engineering of pigs can benefit both biomedicine and agriculture, selecting a suitable gene promoter is critically important. The cytomegalovirus (CMV) promoter, which can robustly drive ubiquitous transgene expression, is commonly used at present, yet recent reports suggest tissue-specific activity in the pig. The objective of this study was to quantify ZsGreen1 protein (in lieu of CMV promoter activity) in tissues from pigs harboring a CMV-ZsGreen1 transgene with a single integration site. Read More

View Article and Full-Text PDF
December 2020

Identification of disease-promoting stromal components by comparative proteomic and transcriptomic profiling of canine mammary tumors using laser-capture microdissected FFPE tissue.

Neoplasia 2021 Apr 29;23(4):400-412. Epub 2021 Mar 29.

Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. Electronic address:

Cancer-associated stroma (CAS) profoundly influences progression of tumors including mammary carcinoma (mCA). Canine simple mCA represent relevant models of human mCA, notably also with respect to CAS. While transcriptomic changes in CAS of mCA are well described, it remains unclear to what extent these translate to the protein level. Read More

View Article and Full-Text PDF