43,303 results match your criteria mechanistic studies

Long intergenic noncoding RNA 00665 promotes proliferation and inhibits apoptosis in colorectal cancer by regulating miR-126-5p.

Aging (Albany NY) 2021 Apr 20;13. Epub 2021 Apr 20.

Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, People’s Republic of China.

Long intergenic noncoding RNAs (lincRNAs) regulate a series of biological processes, and their anomalous expression plays critical roles in the progression of multiple malignancies, including colorectal cancer (CRC). Although many studies have reported the oncogenic function of LINC00665 in multiple cancers, few studies have explored its role in CRC. The aim of this study was to assess the effect of LINC00665 on the malignant behaviors of CRC and explore the underlying regulatory mechanism of LINC00665. Read More

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The effects of myo-inositol vs. metformin on the ovarian function in the polycystic ovary syndrome: a systematic review and meta-analysis.

Eur Rev Med Pharmacol Sci 2021 Apr;25(7):3105-3115

Fertility and Infertility Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Objective: Recent studies have revealed that myo-inositol could be more influential in patients with polycystic ovary syndrome (PCOS). This study was aimed to determine and compare the effects of myo-inositol and metformin on hormonal and metabolic profiles and fertility outcomes.

Materials And Methods: A comprehensive search was carried out among the English-language databases, including PubMed, Scopus, Cochrane Library, Google Scholar, and Web of Science, and the articles published from April 2010 to February 2019 were tracked down. Read More

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Sirtuin Acetylation and Deacetylation: a Complex Paradigm in Neurodegenerative Disease.

Mol Neurobiol 2021 Apr 20. Epub 2021 Apr 20.

Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.

Sirtuins are the class III of histone deacetylases that depend on nicotinamide adenine dinucleotide for their activity. Sirtuins can influence the progression of neurodegenerative disorders by switching between deacetylation and acetylation processes. Histone acetylation occurs when acetyl groups are added to lysine residues on the N-terminal part of histone proteins. Read More

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Inflammation-driven brain and gut barrier dysfunction in stress and mood disorders.

Eur J Neurosci 2021 Apr 20. Epub 2021 Apr 20.

Department of Psychiatry and Neuroscience, Faculty of Medicine and CERVO Brain Research Center, Université Laval, Quebec City, Canada.

Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress vulnerability vs resilience and emotion-related memory encoding. Prevalence of stress and mood disorders such as major depression, bipolar disorder and posttraumatic stress disorder is increasing in our modern societies. Read More

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An Integrated Approach of the Potential Underlying Molecular Mechanistic Paradigms of SARS-CoV-2-Mediated Coagulopathy.

Indian J Clin Biochem 2021 Apr 15:1-17. Epub 2021 Apr 15.

Department of Biochemistry, Maharishi Markandeshwar Institute of Medical Sciences and Research (MMIMSR), Maharishi Markandeshwar University (MMU), Mullana, Ambala, Haryana, India.

Coronavirus disease 2019 (Covid-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic disease which has affected more than 6.2 million people globally, with numbers mounting considerably daily. However, till date, no specific treatment modalities are available for Covid-19 and also not much information is known about this disease. Read More

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Glucagon-Like Peptide 1 Receptor Agonists and Chronic Lower Respiratory Disease Exacerbations Among Patients With Type 2 Diabetes.

Diabetes Care 2021 Apr 19. Epub 2021 Apr 19.

Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL.

Objective: Emerging data from animal and human pilot studies suggest potential benefits of glucagon-like peptide 1 receptor agonists (GLP-1RA) on lung function. We aimed to assess the association of GLP-1RA and chronic lower respiratory disease (CLRD) exacerbation in a population with comorbid type 2 diabetes (T2D) and CLRD.

Research Design And Methods: A new-user active-comparator analysis was conducted with use of a national claims database of beneficiaries with employer-sponsored health insurance spanning 2005-2017. Read More

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The prevalence of occupational exposure to noise: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

Environ Int 2021 Apr 16:106380. Epub 2021 Apr 16.

Workers' Health and Human Ecology Research Center, National School of Public Health Sergio Arouca, Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil. Electronic address:

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of individual experts. Evidence from mechanistic and human data suggests that occupational exposure to noise may cause cardiovascular disease. In this paper, we present a systematic review and meta-analysis of the prevalence of occupational exposure to noise for estimating (if feasible) the number of deaths and disability-adjusted life years from cardiovascular disease that are attributable to exposure to this risk factor, for the development of the WHO/ILO Joint Estimates. Read More

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Frontiers of metal-coordinating drug design.

Expert Opin Drug Discov 2021 May 1;16(5):497-511. Epub 2020 Dec 1.

National Research Council (CNR) of Italy, Institute of Material (IOM) @ International School for Advanced Studies (SISSA), Trieste, Italy.

The occurrence of metal ions in biomolecules is required to exert vital cellular functions. Metal-containing biomolecules can be modulated by small-molecule inhibitors targeting their metal-moiety. As well, the discovery of cisplatin ushered the rational discovery of metal-containing-drugs. Read More

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Construction of 3-Sulfonyl Naphthalenes via Tandem Reaction of 1,4-Diyn-3-yl Esters with Sodium Sulfinates.

J Org Chem 2021 Apr 20. Epub 2021 Apr 20.

Key Laboratory of Functional Molecular Solids (Ministry of Education), Anhui Key Laboratory of Molecular Based Materials, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, China.

Polysubstituted 3-sulfonyl naphthalenes were constructed in good to high yields by AlCl-mediated tandem reaction of 1,4-diyn-3-yl esters and sodium sulfinates. This reaction proceeded under mild reaction conditions and tolerated a variety of functional groups. Moreover, the mechanistic studies indicated that the initial formation of allene under DBU from 1,4-diyn-3-yl ester and a sequence of nucleophilic addition of sodium sulfinate, the formation of allene, and intramolecular cyclization might be involved. Read More

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Rupture, reconstruction, and rehabilitation: A multi-disciplinary review of mechanisms for central nervous system adaptations following anterior cruciate ligament injury.

Knee 2021 Apr 15;30:78-89. Epub 2021 Apr 15.

Ohio Musculoskeletal and Neurological Institute, Ohio University, Athens, OH, USA; Division of Athletic Training, School of Applied Health Sciences and Wellness, College of Health Sciences and Professions, Ohio University, Athens, OH, USA; Division of Physical Therapy, School of Rehabilitation and Communication Sciences, College of Health Sciences and Professions, Ohio University, Athens, OH, USA.

Background: Despite surgical reconstruction and extensive rehabilitation, persistent quadriceps inhibition, gait asymmetry, and functional impairment remain prevalent in patients after anterior cruciate ligament (ACL) injury. A combination of reports have suggested underlying central nervous system adaptations in those after injury govern long-term neuromuscular impairments. The classic assumption has been to attribute neurophysiologic deficits to components of injury, but other factors across the continuum of care (e. Read More

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The upcycled roles of pseudoenzymes in two-component signal transduction.

Curr Opin Microbiol 2021 Apr 16;61:82-90. Epub 2021 Apr 16.

Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, United States. Electronic address:

Upon first glance at a bacterial genome, pseudoenzymes appear unremarkable due to their lack of critical motifs that facilitate catalysis. These pseudoenzymes exist within signal transduction enzymes including histidine kinases, response regulators, diguanylate cyclases, and phosphodiesterases. Here, we summarize recent studies of bacterial pseudo-histidine kinases and pseudo-response regulators that regulate cell division, capsule formation, and the circadian rhythm. Read More

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Vasculitis therapy refines vasculitis mechanistic classification.

Autoimmun Rev 2021 Apr 16:102829. Epub 2021 Apr 16.

Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; Department of Rheumatology, Silkeborg Regional Hospital, Silkeborg, Denmark. Electronic address:

The primary vasculitides constitute a heterogeneous group of immune mediated diseases of incompletely understood pathogenesis currently classified by the size of blood vessels affected (Chapel Hill classification). In recent years, several drugs with well-characterized immunological targets have been tested in clinical trials in large vessel vasculitis and small vessel vasculitis. Such trials provide "reverse translational" or bedside to bench information about underlying pathogenic mechanisms. Read More

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Paricalcitol inhibits oxidative stress-induced cell senescence of the bile duct epithelium dependent on modulating Sirt1 pathway in cholestatic mice.

Free Radic Biol Med 2021 Apr 16. Epub 2021 Apr 16.

Department of Cell Biology, School of Medicine, Taizhou University, Taizhou, PR China. Electronic address:

Background: Clinical studies indicate that vitamin D receptor (VDR) expression is reduced in primary biliary cirrhosis patient livers. However, the mechanism by which activated VDR effect cholestatic liver injury remains unclear.

Methods: Mice were injected intraperitoneally with the VDR agonist paricalcitol or a vehicle 3 days prior to bile duct ligation (BDL) and for 5 or 28 days after surgery. Read More

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The Bisindole Alkaloids Angustilongines M and A from Induce Mitochondrial Apoptosis and G0/G1 Cell Cycle Arrest in HT-29 Cells through Promotion of Tubulin Polymerization.

J Nat Prod 2021 Apr 19. Epub 2021 Apr 19.

Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.

A new linearly fused macroline-sarpagine bisindole, angustilongine M (), was isolated from the methanolic extract of . The structure of the alkaloid was elucidated based on analysis of the spectroscopic data, and its biological activity was evaluated together with another previously reported macroline-akuammiline bisindole from the same plant, angustilongine A (). Compounds and showed pronounced in vitro growth inhibitory activity against a wide panel of human cancer cell lines. Read More

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The "weak base route" leading to transition metal-N-heterocyclic carbene complexes.

Chem Commun (Camb) 2021 Apr 26;57(32):3836-3856. Epub 2021 Mar 26.

Department of Chemistry and Centre for Sustainable Chemistry, Ghent University, Building S3, Krijgslaan 281, 9000 Gent, Belgium.

N-Heterocyclic carbenes (NHCs) are nowadays ubiquitous in organometallic chemistry and catalysis. Recently, a synthetic method which makes use of weak bases and desirable solvents has emerged as a simple, widely applicable and cost-effective pathway to well defined M-NHC complexes. Herein, recent studies devoted to the weak base approach are examined in detail, in order to showcase the simplicity, scope and variations of the method with regards to the azolium salts, bases and the metal sources, as well as the reaction conditions used. Read More

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B(CF)-catalyzed tandem protonation/deuteration and reduction of -formed enamines.

Rongpei Wu Ke Gao

Org Biomol Chem 2021 Apr 19. Epub 2021 Apr 19.

College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan, Hubei, P.R. China.

A highly efficient B(C6F5)3-catalyzed tandem protonation/deuteration and reduction of in situ-formed enamines in the presence of water and pinacolborane was developed. Regioselective β-deuteration of tertiary amines was achieved with high chemo- and regioselectivity. D2O was used as a readily available and cheap source of deuterium. Read More

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A simplified approach for derivation of induced pluripotent stem cells from Epstein-Barr virus immortalized B-lymphoblastoid cell lines.

Heliyon 2021 Apr 3;7(4):e06617. Epub 2021 Apr 3.

Department of Rehabilitation Medicine and the Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA.

Given the limited availability of tissue, especially brain tissue, for neurological diseases and disorders research, the development of alternative biological tools for investigations of underlying molecular and genetic mechanisms is imperative. One important resource for this task is the large repositories that bank immortalized blood cells (i.e. Read More

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No Evidence for Trade-Offs Between Lifespan, Fecundity, and Basal Metabolic Rate Mediated by Liver Fatty Acid Composition in Birds.

Front Cell Dev Biol 2021 29;9:638501. Epub 2021 Mar 29.

Institute of Vertebrate Biology, Czech Academy of Sciences, Brno, Czechia.

The fatty acid composition of biological membranes has been hypothesised to be a key molecular adaptation associated with the evolution of metabolic rates, ageing, and life span - the basis of the membrane pacemaker hypothesis (MPH). MPH proposes that highly unsaturated membranes enhance cellular metabolic processes while being more prone to oxidative damage, thereby increasing the rates of metabolism and ageing. MPH could, therefore, provide a mechanistic explanation for trade-offs between longevity, fecundity, and metabolic rates, predicting that short-lived species with fast metabolic rates and higher fecundity would have greater levels of membrane unsaturation. Read More

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Could We Address the Interplay Between CD133, Wnt/β-Catenin, and TERT Signaling Pathways as a Potential Target for Glioblastoma Therapy?

Front Oncol 2021 1;11:642719. Epub 2021 Apr 1.

Department of Biochemistry, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Malaysia.

Glioblastoma multiforme (GBM) is one of the most lethal forms of primary brain tumors. Glioblastoma stem cells (GSCs) play an undeniable role in tumor development by activating multiple signaling pathways such as Wnt/β-catenin and PI3K/AKT/mTOR that facilitate brain tumor formation. CD133, a transmembrane glycoprotein, has been used to classify cancer stem cells (CSCs) in GBM. Read More

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Association Between Antibiotic Treatment and the Efficacy of Intravesical BCG Therapy in Patients With High-Risk Non-Muscle Invasive Bladder Cancer.

Front Oncol 2021 2;11:570077. Epub 2021 Apr 2.

Department of Urology, Center for Urologic Cancer, National Cancer Center, Goyang, South Korea.

Objective: To investigate the association between antibiotic therapy and the efficacy of intravesical BCG therapy in patients with high-risk non-muscle invasive bladder cancer (NMIBC).

Methods: This study involved the retrospective review of medical records of patients who underwent transurethral resection of bladder tumors for high-risk NMIBC followed by intravesical BCG therapy between 2008 and 2017. Patients were categorized as none, short- (2-6 days), and long-course use (≥7 days) based on the duration of antibiotic treatment concurrent with or initiated ≤30 days before BCG therapy. Read More

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Microbiome dysbiosis and alcoholic liver disease.

Liver Res 2019 Dec 6;3(3-4):218-226. Epub 2019 Sep 6.

Department of Medicine, Department of Pharmacology and Toxicology, Alcohol Research Center, University of Louisville, Louisville, KY, USA.

Microbiome dysbiosis is strongly associated with alcoholic liver disease (ALD). Recent studies on comprehensive analyses of microbiome compositional and functional changes have begun to uncover the mechanistic relation between microbiome and the pathogenesis of ALD. Importantly, targeting the microbiome has become a potential strategy for the prevention and treatment of ALD. Read More

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December 2019

β-asarone suppresses HCT116 colon cancer cell proliferation and liver metastasis in part by activating the innate immune system.

Oncol Lett 2021 Jun 31;21(6):435. Epub 2021 Mar 31.

Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.

Studies have revealed that β-asarone exerts a powerful inhibitory effect on the proliferation of human cancer cells. The authors' previous study demonstrated that β-asarone could induce LoVo colon cancer cell apoptosis and , indicating its anticancer properties. The present study aimed to determine the antineoplastic effect of β-asarone in HCT116 colon cancer cells. Read More

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Antiviral Activity of Interferon Alpha-Inducible Protein 27 Against Hepatitis B Virus Gene Expression and Replication.

Front Microbiol 2021 31;12:656353. Epub 2021 Mar 31.

State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.

Despite the availability of effective vaccines, hepatitis B virus (HBV) is still a major health issue, and approximately 350 million people have been chronically infected with HBV throughout the world. Interferons (IFNs) are the key molecules in the innate immune response that restrict several kinds of viral infections the induction of hundreds of IFN-stimulated genes (ISGs). The objective of this study was to confirm if interferon alpha-inducible protein 27 (IFI27) as an ISG could inhibit HBV gene expression and DNA replication both in cell culture and in a mouse model. Read More

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Betulinic acid inhibits pyroptosis in spinal cord injury by augmenting autophagy via the AMPK-mTOR-TFEB signaling pathway.

Int J Biol Sci 2021 11;17(4):1138-1152. Epub 2021 Mar 11.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.

Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. Read More

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A Mild One-Pot Reduction of Phosphine(V) Oxides Affording Phosphines(III) and Their Metal Catalysts.

Organometallics 2021 Mar 5;40(6):693-701. Epub 2021 Mar 5.

Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Żwirki i Wigury Street 101, 02-089 Warsaw, Poland.

The metal-free reduction of a range of phosphine(V) oxides employing oxalyl chloride as an activating agent and hexachlorodisilane as reducing reagent has been achieved under mild reaction conditions. The method was successfully applied to the reduction of industrial waste byproduct triphenylphosphine(V) oxide, closing the phosphorus cycle to cleanly regenerate triphenylphosphine(III). Mechanistic studies and quantum chemical calculations support the attack of the dissociated chloride anion of intermediated phosphonium salt at the silicon of the disilane as the rate-limiting step for deprotection. Read More

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mTORC1/rpS6 and p-FAK-Y407 signaling regulate spermatogenesis: Insights from studies of the adjudin pharmaceutical/toxicant model.

Semin Cell Dev Biol 2021 Apr 15. Epub 2021 Apr 15.

The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong, Jiangsu 226001, China; The Population Council, Center for Biomedical Research, 1230 York Ave, New York, NY 10065, United States. Electronic address:

In rodents and humans, the major cellular events at spermatogenesis include self-renewal of spermatogonial stem cells and undifferentiated spermatogonia via mitosis, commitment of spermatogonia to differentiation and transformation to spermatocytes, meiosis, spermiogenesis, and the release of spermatozoa at spermiation. While details of the morphological changes during these cellular events have been delineated, knowledge gap exists between the morphological changes in the seminiferous epithelium and the underlying molecular mechanism(s) that regulate these cellular events. Even though many of the regulatory proteins and biomolecules that modulate spermatogenesis are known based on studies using genetic models, the underlying regulatory mechanism(s), in particular signaling pathways/proteins, remain unexplored since much of the information regarding the signaling regulation is unknown. Read More

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Prior transient exposure to interleukin-21 delivered by recombinant adeno-associated virus vector protects mice from hepatitis B virus persistence.

Antiviral Res 2021 Apr 15:105076. Epub 2021 Apr 15.

Key Laboratory of Medical Molecular Virology, Department of Microbiology and Parasitology, School of Basic Medical Sciences, Fudan University, Shanghai, China; Songjiang District Central Hospital, Shanghai, China. Electronic address:

Chronic infection of hepatitis B virus (HBV) is a high risk factor for hepatic diseases, such as liver fibrosis, cirrhosis and hepatocellular carcinoma. Non-responders and hyporesponders to HBV vaccine are not protected from HBV infection. Patients that achieve autonomous or treatment-induced recovery are at risk of reactivation due to persistence of HBV covalently closed circular DNA (cccDNA) in hepatocytes. Read More

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Mechanistic evaluation of a novel cyclohexanone derivative's functionality against nociception and inflammation: an in-vitro, in-vivo and in-silico approach.

Eur J Pharmacol 2021 Apr 15:174091. Epub 2021 Apr 15.

School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB. UK.

The synthesis of a novel cyclohexanone derivative (CHD; Ethyl 6-(4-metohxyphenyl)-2-oxo-4-phenylcyclohexe-3-enecarboxylate) was described and the subsequent aim was to perform an in vitro, in vivo and in silico pharmacological evaluation as a putative anti-nociceptive and anti-inflammatory agent in mice. Initial in vitro studies revealed that CHD inhibited both cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzymes and it also reduced mRNA expression of COX-2 and the pro-inflammatory cytokines TNF-α and IL-1β. It was then shown that CHD dose dependently inhibited chemically induced tonic nociception in the abdominal constriction assay and also phasic thermal nociception (i. Read More

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Mechanistic Insights from REDUCE-IT STRENGTHen the Case Against Triglyceride Lowering as a Strategy for Cardiovascular Disease Risk Reduction.

Am J Med 2021 Apr 14. Epub 2021 Apr 14.

University of Colorado Anschutz Medical Campus, Aurora, CO.

Elevated triglyceride (TG) levels have been linked to residual atherosclerotic cardiovascular risk in patients with controlled low-density lipoprotein cholesterol (LDL-C). However, outcome trials testing TG-lowering agents have failed to demonstrate cardiovascular risk reduction in statin-treated subjects. One such example is the recent STRENGTH trial, which tested mixed omega fatty acids (n3-FAs, 4g/d) in high-risk patients with elevated TGs. Read More

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Combination of resveratrol and green tea epigallocatechin gallate induces synergistic apoptosis and inhibits tumor growth in head and neck cancer models.

Oncol Rep 2021 May 13;45(5). Epub 2021 Apr 13.

Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.

Despite widespread interest in chemoprevention and therapy due to the high margin of safety of dietary natural compounds, clinical intervention with single agents has failed to yield the expected outcomes, mostly due to poor bioavailability and low potency. Combinations of natural agents with synergistic effects are gaining increasing attention. In the present study, and antitumor effects of a combination of two natural dietary agents, green tea epigallocatechin gallate (EGCG) and resveratrol were investigated. Read More

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