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Control of intestinal epithelial permeability by lysophosphatidic acid receptor 5.

Cell Mol Gastroenterol Hepatol 2021 May 8. Epub 2021 May 8.

Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Gastroenterology Research, Atlanta Veterans Administration Medical Center, Decatur, GA, USA; Winship Cancer Institute, Emory University School of Medicine. Electronic address:

Background & Aims: Epithelial cells form a monolayer at mucosal surface that functions as a highly selective barrier. Lysophosphatidic acid (LPA) is a bioactive lipid that elicits a broad range of biological effects via cognate G protein-coupled receptors. LPA receptor 5 (LPA) is highly expressed in intestinal epithelial cells, but its role in the intestine is not well known. Read More

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Ubiquitin ligases in cancer: functions and clinical potentials.

Cell Chem Biol 2021 Apr 27. Epub 2021 Apr 27.

Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA; Howard Hughes Medical Institute, NYU Grossman School of Medicine, New York, NY, USA. Electronic address:

Ubiquitylation, a highly regulated post-translational modification, controls many cellular pathways that are critical to cell homeostasis. Ubiquitin ligases recruit substrates and promote ubiquitin transfer onto targets, inducing proteasomal degradation or non-degradative signaling. Accumulating evidence highlights the critical role of dysregulated ubiquitin ligases in processes associated with the initiation and progression of cancer. Read More

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Structural Heterogeneity of Human Histone H2A.1.

J Phys Chem B 2021 May 11. Epub 2021 May 11.

Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, United States.

Histones are highly basic chromatin proteins that tightly package and order eukaryotic DNA into nucleosomes. While the atomic structure of the nucleosomes has been determined, the three-dimensional structure of DNA-free histones remains unresolved. Here, we combine tandem nonlinear and linear ion mobility spectrometry (FAIMS-TIMS) coupled to mass spectrometry in parallel with molecular modeling to study the conformational space of a DNA-free histone H2A type 1 (H2A. Read More

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Second-generation hormonotherapy in prostate cancer and bone microenvironment.

Endocr Relat Cancer 2021 May 1. Epub 2021 May 1.

A Guillot, Medical oncology, Institut de Cancérologie de la Loire, Saint Priest en Jarez, France.

Prostate cancer (Pca) is the most commonly diagnosed cancer affecting men in France. Before the age of 75 years old, 1 in 8 French men will have Pca. Androgen deprivation therapies (ADT) remain the standard of care. Read More

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Integrated profiling identifies ITGB3BP as prognostic biomarker for hepatocellular carcinoma.

Bosn J Basic Med Sci 2021 Apr 12. Epub 2021 Apr 12.

Department of Epidemiology and Statistics, School of Public Health, Guangxi Medical University, Nanning, China; Key Laboratory of High-Incidence-Tumor Prevention and Treatment, Guangxi Medical University, Ministry of Education, Nanning, China.

Hepatocellular carcinoma (HCC) is a highly malignant tumor. In this study, we sought to identify a novel biomarker for HCC by analyzing transcriptome and clinical data. The R software was used to analyze the differentially expressed genes (DEGs) in the datasets GSE74656 and GSE84598 downloaded from the Gene Expression Omnibus database, followed by a functional annotation. Read More

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PAL-mediated SA biosynthesis pathway contributes to nematode resistance in wheat.

Plant J 2021 May 11. Epub 2021 May 11.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.

The pathogen cereal cyst nematode (CCN) is deleterious to Triticeae crops and is a threat to the global crop yield. Accession No.1 of Aegilops variabilis, a relative of bread wheat, is highly resistant to CCN. Read More

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Metal Modulation: An Easy-to-Implement Tactic for Tuning Lanthanide Phototheranostics.

J Am Chem Soc 2021 May 11. Epub 2021 May 11.

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.

Phototheranostics constitute an emerging cancer treatment wherein the core diagnostic and therapeutic functions are integrated into a single photosensitizer (PS). Achieving the full potential of this modality requires being able to tune the photosensitizing properties of the PS in question. Structural modification of the organic framework represents a time-honored strategy for tuning the photophysical features of a given PS system. Read More

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Evolution of the world's only alpine parrot - genomic adaptation or phenotypic plasticity, behaviour and ecology?

Mol Ecol 2021 May 10. Epub 2021 May 10.

Department of Anatomy, University of Otago, Dunedin, New Zealand.

Climate warming, in particular in island environments, where opportunities for species to disperse are limited, may become a serious threat to cold adapted alpine species. In order to understand how alpine species may respond to a warming world, we need to understand the drivers that have shaped their habitat specialisation and the evolutionary adaptations that allow them to utilize alpine habitats. The endemic, endangered New Zealand kea (Nestor notabilis) is considered the only alpine parrot in the world. Read More

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Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis.

Front Med 2021 May 11. Epub 2021 May 11.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.

Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism, which is manifested by increased endogenous fat mobilization, hypertriglyceridemia, and increased fatty acid synthesis. Fatty acid synthase (FASN) is a key enzyme for the de novo synthesis of fatty acids, and monoacylglycerol esterase (MGLL) is an important metabolic enzyme that converts triglycerides into free fatty acids. Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways, the most common of which is the PI3K-AKT signaling pathway. Read More

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African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors associated with immunologic functions and environmental exposures.

Sci Rep 2021 May 10;11(1):9905. Epub 2021 May 10.

Bioinformatics and Computational Biology Program, Iowa State University, Ames, IA, 50011, USA.

The COVID-19 pandemic has affected African American populations disproportionately with respect to prevalence, and mortality. Expression profiles represent snapshots of combined genetic, socio-environmental (including socioeconomic and environmental factors), and physiological effects on the molecular phenotype. As such, they have potential to improve biological understanding of differences among populations, and provide therapeutic biomarkers and environmental mitigation strategies. Read More

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Global declines in coral reef calcium carbonate production under ocean acidification and warming.

Proc Natl Acad Sci U S A 2021 May;118(21)

Oceans Graduate School and Oceans Institute, The University of Western Australia, Crawley 6009, WA, Australia.

Ocean warming and acidification threaten the future growth of coral reefs. This is because the calcifying coral reef taxa that construct the calcium carbonate frameworks and cement the reef together are highly sensitive to ocean warming and acidification. However, the global-scale effects of ocean warming and acidification on rates of coral reef net carbonate production remain poorly constrained despite a wealth of studies assessing their effects on the calcification of individual organisms. Read More

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Progress on biosynthesis and function of the natural products of Zi Cao as a traditional Chinese medicinal herb.

Yi Chuan 2021 May;43(5):459-472

State Key Laboratory of Pharmaceutical Biotechnology, Institute for Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing 210023, China.

Zi Cao is an important traditional medicinal plant resource in China. Shikonin and its derivatives, as the purple-red naphthoquinones among natural products of its roots, are commonly used clinically in the treatment of sores and skin inflammations. Over the past few decades, due to their highly effective multiple biological activities, pharmacological effects, good clinical efficacy and high utilization value, shikonin and its derivatives have attracted increasing attention of domestic and foreign researchers. Read More

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Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma.

Cancer Res Treat 2021 May 11. Epub 2021 May 11.

Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.

Purpose: Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and NF-κB pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells. Read More

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Protein expression and purification of G-protein coupled receptor kinase 6 (GRK6), toward structure-based drug design and discovery for multiple myeloma.

Protein Expr Purif 2021 May 7:105890. Epub 2021 May 7.

Center for Applied Structural Discovery, Biodesign Institute at Arizona State University, Tempe, AZ, 85281, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ, 85287, USA. Electronic address:

Human G-protein coupled receptor kinase 6 (GRK6) belongs to the GRK4 kinase subfamily of the G protein-coupled receptor kinase family which comprises of GRK1, GRK2, and GRK4. These kinases phosphorylate ligand-activated G-protein coupled receptors (GPCRs), driving heterotrimeric G protein coupling, desensitization of GPCR, and β-arrestin recruitment. This reaction series mediates cellular signal pathways for cell survival, proliferation, migration and chemotaxis. Read More

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Macrophage activation in the lung during the progression of nitrogen mustard induced injury is associated with histone modifications and altered miRNA expression.

Toxicol Appl Pharmacol 2021 May 7:115569. Epub 2021 May 7.

Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 08854, USA; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA. Electronic address:

Activated macrophages have been implicated in lung injury and fibrosis induced by the cytotoxic alkylating agent, nitrogen mustard (NM). Herein, we determined if macrophage activation is associated with histone modifications and altered miRNA expression. Treatment of rats with NM (0. Read More

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Phosphatidylinositol 3-kinase (PI3K) inhibitors: a recent update on inhibitor design and clinical trials (2016-2020).

Expert Opin Ther Pat 2021 May 10. Epub 2021 May 10.

DSC 362, Department of Chemistry, The University of Nebraska at Omaha, 6001 Dodge Street, Omaha, Nebraska 68182, USA.

Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in regulating cell growth and proliferation and thus have been considered as effective anticancer drug targets. Many PI3K inhibitors have been developed and progressed to various stages of clinical trials and some even have been approved in recent years by the regulatory agency as anticancer treatment. In this review, we discuss the drug design and clinical development of PI3K inhibitors in the past four years. Read More

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Genomic correlates of response and resistance to immune checkpoint inhibitors in carcinomas of unknown primary.

Eur J Clin Invest 2021 May 10:e13583. Epub 2021 May 10.

University of Ioannina, Ioannina, Greece.

Background: Cancers of unknown primary (CUP) are highly aggressive tumours with limited molecular characterization. These tumours can be particularly sensitive to immune checkpoint inhibitors (ICI) by mounting a seemingly more effective anti-tumour immune response. Unlike other tumour lineages, the biological basis and clinical efficacy of ICI in CUP remain largely unknown. Read More

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A highly stable multifunctional aptamer for enhancing antitumor immunity against hepatocellular carcinoma by blocking dual immune checkpoints.

Biomater Sci 2021 May 10. Epub 2021 May 10.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China. and Fujian Institute of Research on The Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, P. R. China.

T-lymphocytes play a potent role in cancer immunotherapy; while, limited tumor infiltrating lymphocytes (TILs) combined with severe immunosuppression always significantly hinder their antitumor immune responses, especially in solid tumors such as hepatocellular carcinoma (HCC). Here, we prepared a highly stable multifunctional aptamer for strengthening antitumor immunity against HCC solid tumors through a dual immune checkpoint blockade of CTLA-4 and PD-L1. The engineered multifunctional aptamer (termed P1/C4-bi-apt) can block both CTLA-4/B7 and PD-1/PD-L1 signaling pathways and thus enhance the antitumor immune responses. Read More

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Glycogen synthase kinase 3β promotes osteosarcoma invasion and migration via regulating PTEN and phosphorylation of focal adhesion kinase.

Biosci Rep 2021 May 10. Epub 2021 May 10.

Harbin Medical University Cancer Hospital, Harbin, China.

Aim: Typical features of human osteosarcoma are highly invasive and migratory capacities. Our study aimed to investigate the roles of glycogen synthase kinase 3β (GSK3β) in human osteosarcoma metastasis.

Methods: GSK3β expressions in clinical osteosarcoma tissues with or without metastasis were examined by immunohistochemical staining. Read More

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Bayesian integrative analysis and prediction with application to atherosclerosis cardiovascular disease.

Biostatistics 2021 May 10. Epub 2021 May 10.

Division of Biostatistics, University of Minnesota, 20 Delaware St SE, Minneapolis, MN 55455, USA.

The problem of associating data from multiple sources and predicting an outcome simultaneously is an important one in modern biomedical research. It has potential to identify multidimensional array of variables predictive of a clinical outcome and to enhance our understanding of the pathobiology of complex diseases. Incorporating functional knowledge in association and prediction models can reveal pathways contributing to disease risk. Read More

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Identification of Prognostic Glycolysis-Related lncRNA Signature in Tumor Immune Microenvironment of Hepatocellular Carcinoma.

Front Mol Biosci 2021 22;8:645084. Epub 2021 Apr 22.

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.

The purpose of this study was to construct a novel risk scoring model with prognostic value that could elucidate tumor immune microenvironment of hepatocellular carcinoma (HCC). Data were obtained through The Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis were carried out to screen for glycolysis-related long noncoding RNAs (lncRNAs) that could provide prognostic value. Read More

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Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer.

Front Oncol 2021 22;11:650453. Epub 2021 Apr 22.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Increasing evidence shows that the extracellular matrix (ECM) is an important regulator of breast cancer (BC). The ECM comprises of highly variable and dynamic components. Compared with normal breast tissue under homeostasis, the ECM undergoes many changes in composition and organization during BC progression. Read More

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Identifying potential drug targets and candidate drugs for COVID-19: biological networks and structural modeling approaches.

F1000Res 2021;10:127. Epub 2021 Feb 18.

Centre of Interdisciplinary Science-Computational Life Sciences, College of Chemistry and Chemical Engineering,, Henan University of Technology, Zhengzhou, Henan, 450001, China.

Coronavirus (CoV) is an emerging human pathogen causing severe acute respiratory syndrome (SARS) around the world. Earlier identification of biomarkers for SARS can facilitate detection and reduce the mortality rate of the disease. Thus, by integrated network analysis and structural modeling approach, we aimed to explore the potential drug targets and the candidate drugs for coronavirus medicated SARS. Read More

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February 2021

Tetraspanins as Potential Therapeutic Candidates for Targeting Flaviviruses.

Front Immunol 2021 21;12:630571. Epub 2021 Apr 21.

Department of Biological Sciences, Old Dominion University, Norfolk, VA, United States.

Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. Read More

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Co-infection of H9N2 Influenza A Virus and in a BALB/c Mouse Model Aggravates Lung Injury by Synergistic Effects.

Front Microbiol 2021 21;12:670688. Epub 2021 Apr 21.

Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.

Pathogens that cause respiratory diseases in poultry are highly diversified, and co-infections with multiple pathogens are prevalent. The H9N2 strain of avian influenza virus (AIV) and () are common poultry pathogens that limit the development of the poultry industry. This study aimed to clarify the interaction between these two pathogens and their pathogenic mechanism using a mouse model. Read More

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Metabolic Homeostasis in Life as We Know It: Its Origin and Thermodynamic Basis.

Front Physiol 2021 23;12:658997. Epub 2021 Apr 23.

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Living organisms require continuous input of energy for their existence. As a result, life as we know it is based on metabolic processes that extract energy from the environment and make it available to support life (energy metabolism). This metabolism is based on, and regulated by, the underlying thermodynamics. Read More

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Effects of Real-Ambient PM Exposure on Lung Damage Modulated by Nrf2.

Front Pharmacol 2021 23;12:662664. Epub 2021 Apr 23.

School of Public Health, Qingdao University, Qingdao, China.

Previous studies have shown that long-term exposure to fine particulate matter (PM) increases the morbidity and mortality of pulmonary diseases such as asthma, chronic obstructive pulmonary disease and pulmonary emphysema. Oxidative stress and inflammation play key roles in pulmonary damage caused by PM. Nuclear factor erythroid 2-related factor 2 (Nrf2) could regulate the expression of antioxidant and anti-inflammatory genes and is pivotal for protection against PM-induced oxidative stress. Read More

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[Molecular mechanisms of highly pathogenic viruses' replication and their applications for a novel drug discovery].

Authors:
Shuzo Urata

Uirusu 2020 ;70(1):69-82

National Research Center for the Control and Prevention of Infectious Diseases (CCPID)/Institute of Tropical Medicine (NEKKEN), Nagasaki University.

Productive (lytic) replication of DNA viruses elicits host cell DNA damage responses, which cause both beneficial and detrimental effects on viral replication. Viruses utilize them and selectively cancel the 'noisy' downstream signaling pathways, leading to maintain high S-phase CDK activities required for viral replication. To achieve this fine tuning of cellular environment, herpesviruses encode many (>70) genes in their genome, which are expressed in a strictly regulated temporal cascade (immediate-early, early, and late). Read More

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January 2020

A Scheme for Inferring Viral-Host Associations based on Codon Usage Patterns Identifies the Most Affected Signaling Pathways during COVID-19.

J Biomed Inform 2021 May 6:103801. Epub 2021 May 6.

Network Reconstruction & Analysis (NetRA) Lab, Department of Computer Applications, Sikkim University, Gangtok, India. Electronic address:

Understanding the molecular mechanism of COVID-19 disease pathogenesis helps in the rapid development of therapeutic targets. Usually, viral protein targets host proteins in an organized fashion. The expression of any viral gene depends mostly on the host translational machinery. Read More

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Future of immunotherapy in pancreas cancer and the trials, tribulations and successes thus far.

Semin Oncol 2021 Apr 17. Epub 2021 Apr 17.

Division of Hematology and Oncology, Columbia University Irving Medical Center, and New York Presbyterian Hospital, New York, NY. Electronic address:

Pancreas ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival rate of 10%. Currently, chemotherapy remains the standard of care for systemic treatment. Immunotherapy with checkpoint inhibitors unfortunately has not been found to be effective in the treatment of PDAC to date, likely due to the highly desmoplastic and immunosuppressive tumor microenvironment (TME). Read More

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