271,273 results match your criteria inhibitory effects


Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors.

Eur J Med Chem 2021 Apr 24;220:113501. Epub 2021 Apr 24.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.

Lysine-specific demethylase 1 (LSD1) is a FAD-dependent enzyme, which has been proposed as a promising target for therapeutic cancer. Herein, a series of benzofuran derivatives were designed, synthesized and biochemical evaluated as novel LSD1 inhibitors based on scaffold hopping and conformational restriction strategy. Most of the compounds potently suppressed the enzymatic activities of LSD1 and potently inhibited tumor cells proliferation. Read More

View Article and Full-Text PDF

The Role of the Excitation:Inhibition Functional Balance in the mPFC in the Onset of Antidepressants.

Neuropharmacology 2021 May 1:108573. Epub 2021 May 1.

Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing, China; Beijing Institute of Basic Medical Sciences, Beijing, China. Electronic address:

Currently available antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), generally require weeks to months to produce a therapeutic response, but the mechanism of action underlying the delayed onset of antidepressant-like action remains to be elucidated. The balance between excitatory glutamatergic pyramidal neurons and inhibitory γ-aminobutyric acid (GABA) interneurons, i.e. Read More

View Article and Full-Text PDF

Perineuronal net abnormalities in Slc13a4 mice are rescued by postnatal administration of N-acetylcysteine.

Exp Neurol 2021 May 1:113734. Epub 2021 May 1.

The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address:

Disruptions to either sulfate supply or sulfation enzymes can affect brain development and have long-lasting effects on brain function, yet our understanding of the molecular mechanisms governing this are incomplete. Perineuronal nets (PNNs) are highly sulfated, specialized extracellular matrix structures that regulate the maturation of synaptic connections and neuronal plasticity. We have previously shown that mice heterozygous for the brain sulfate transporter Slc13a4 have abnormal social interactions, memory, exploratory behaviors, stress and anxiety of postnatal origin, pointing to potential deficits in PNN biology, and implicate SLC13A4 as a critical factor required for regulating normal synaptic connectivity and function. Read More

View Article and Full-Text PDF

Circ_0017956 promotes the proliferation and metastasis of non-small cell lung cancer through regulating miR-515-5p/ITGB8 axis.

Authors:
Na Li Dan Zhu

Cell Cycle 2021 May 4:1-13. Epub 2021 May 4.

Department of Respiratory, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.

Circular RNAs (circRNAs) have been reported to exert vital roles in the tumorigenesis of non-small cell lung cancer (NSCLC). The study aimed to probe the function of circ_0017956 in NSCLC development. The expression of circ_0017956, microRNA (miR)-515-5p and integrin subunit beta 8 (ITGB8) was gauged by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Read More

View Article and Full-Text PDF

MiR-206 promotes extracellular matrix accumulation and relieves infantile hemangioma through targeted inhibition of DNMT3A.

Cell Cycle 2021 May 4:1-15. Epub 2021 May 4.

Department of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.

MiR-206 is abnormally expressed in infant hemangioma endothelial cells (HemECs), but the mechanism is not clear. We explored the intervention of miR-206 in HemECs in relation to extracellular matrix (ECM) metabolism. We selected 48 cases of infantile hemangioma (IH) from volunteer organizations. Read More

View Article and Full-Text PDF

Inhibitory effect of HTLV-1 infection on the production of B-cell activating factors in established follicular dendritic cell-like cells.

Immun Inflamm Dis 2021 May 4. Epub 2021 May 4.

Division of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Introduction: The low frequency of ectopic germinal center in labial salivary glands of patients with human T-cell leukemia virus type 1 (HTLV-1) antibody-positive Sjögren's syndrome (SS) suggests that HTLV-1 has some effects on follicular dendritic cells (FDCs).

Methods: We used flow cytometry, immunofluorescence, and enzyme-linked immunosorbent assays (ELISAs) to investigate the direct effect of HTLV-1 on B-cell activating factors produced by established FDC like cells obtained from excised human tonsils. We then measured the serum B-cell activating factor (BAFF) and C-X-C motif ligand (CXCL) 13 concentrations of the HTLV-1-seropositive SS patients and the HTLV-1-seronegative SS patients by ELISA. Read More

View Article and Full-Text PDF

lncRNA Mirt2 upregulates miR-1246 through methylation to suppress LPS-induced lung cell apoptosis.

Immun Inflamm Dis 2021 May 4. Epub 2021 May 4.

Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Introduction: Long noncoding RNA Mirt2 has been proven to be a suppressor of lipopolysaccharide (LPS) (a key player in sepsis)-induced inflammation responses. Therefore, Mirt2 may also participate in sepsis. This study was carried out to analyze the interactions between Mirt2 and microRNA-1246 (miR-1246) in sepsis, with a specific focus on sepsis-induced acute lung injury (sepsis-ALI). Read More

View Article and Full-Text PDF

Effect of lncRNA-ATB/miR-651-3p/Yin Yang 1 pathway on trophoblast-endothelial cell interaction networks.

J Cell Mol Med 2021 May 4. Epub 2021 May 4.

Department of Obstetrics and Gynecology, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.

Our previous studies have confirmed that lncRNA-ATB may be involved in the pathogenesis of preeclampsia, however, it is uncertain whether lncRNA-ATB influence the interaction between trophoblast and endothelial cells, which is crucial to the uterine spiral artery remodelling. Scratch wound healing and transwell invasion assay were conducted to test the migration and invasion of trophoblast cells. Co-culture model was used to simulate the physiological environment in vivo. Read More

View Article and Full-Text PDF

Opposing effects of dopamine on agonistic behaviour in crayfish.

J Exp Biol 2021 May 4. Epub 2021 May 4.

Department of Biology, Faculty of Science, Yamagata University, 990-8560 Yamagata, Japan.

The effects of dopamine on the agonistic behaviour of crayfish were analysed. When dopamine concentrations of 1 µM were injected into large crayfish, individuals were beaten by smaller opponents, despite their physical advantage. Injection of 10 µM dopamine into small animals increased their winning rate against larger opponents. Read More

View Article and Full-Text PDF

Plasma Cell Proliferation Is Reduced in Myeloma-Induced Hypercalcemia and in Co-Culture with Normal Healthy BM-MSCs.

Lab Med 2021 May;52(3):273-289

Department of Hematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Objective: In multiple myeloma (MM), stimulation of osteoclasts and bone marrow (BM) lesions lead to hypercalcemia, renal failure, and anemia. Co-culture of the myeloma cells in both hypocalcemia and hypercalcemia concentrations with bone marrow-mesenchymal stem cells were evaluated.

Materials And Methods: Viability and survival of myeloma cells were assessed by microculture tetrazolium test and flow cytometric assays. Read More

View Article and Full-Text PDF

Gold Cluster Capped with a BCL-2 Antagonistic Peptide Exerts Synergistic Antitumor Activity in Chronic Lymphocytic Leukemia Cells.

ACS Appl Mater Interfaces 2021 May 4. Epub 2021 May 4.

Department of Chemistry and Biology, Faculty of Environment and Life Science, Beijing University of Technology, Beijing 100124, China.

Chronic lymphocytic leukemia (CLL) is still incurable by conventional chemotherapy due to the resistance to apoptosis. We have previously found that a peptide-capped gold cluster (AuSv) can target on the aberrant oxidative stress in CLL cells to specially inhibit thioredoxin reductase (TrxR) activity, resulting in significant apoptosis. However, the required doses of the gold cluster for inducing apoptosis are high, restricting its potential for further applications. Read More

View Article and Full-Text PDF

A Phase 1 Study to Investigate the Effects of Cortexolone 17α-Propionate, Also Known as Clascoterone, on the QT Interval Using the Meal Effect to Demonstrate ECG Assay Sensitivity.

Clin Pharmacol Drug Dev 2021 May 3. Epub 2021 May 3.

St George's, University of London, London, United Kingdom.

Cortexolone 17α-propionate, also known as clascoterone, is a potent androgen receptor inhibitor intended for the topical treatment of skin diseases associated with androgenic pathway alterations. In nonclinical studies, cortexolone 17α-propionate was found to have a weak inhibitory effect on human Ether-à-go-go-Related Gene (hERG) potassium channels, which are vital for normal electrical activity in the heart. When used in a cream formulation, little cortexolone 17α-propionate is absorbed. Read More

View Article and Full-Text PDF

Elimination of human cytomegalovirus DNA degradation in urine.

J Med Virol 2021 May 3. Epub 2021 May 3.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Centers of Biological Products, School of Life Science and School of Public Health, Xiamen University, Xiamen, Fujian, China.

Congenital cytomegalovirus infection (cCMVi) is an important cause of sensorineural hearing loss in newborns. Detection of human cytomegalovirus (HCMV) DNA in urine has been used to screen for cCMVi in newborns. However, the matrix effect of urine on HCMV DNA detection is unclear. Read More

View Article and Full-Text PDF

Isorhynchophylline Relieves Ferroptosis-Induced Nerve Damage after Intracerebral Hemorrhage Via miR-122-5p/TP53/SLC7A11 Pathway.

Neurochem Res 2021 May 3. Epub 2021 May 3.

Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Medical University, No. 167 Fangdong Street, Xi'an, 710038, China.

Isorhynchophylline (IRN), a component of traditional Chinese herb Uncaria rhynchophylla, possesses strong antioxidant activity. Ferroptosis induced by iron overload causes cell oxidative stress after intracerebral hemorrhage (ICH). Therefore, this study aims to explore the effects of IRN on the ferroptosis following ICH. Read More

View Article and Full-Text PDF

Inhibitory effects of aprotinin on influenza A and B viruses in vitro and in vivo.

Sci Rep 2021 May 3;11(1):9427. Epub 2021 May 3.

Department of Pharmacy, College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong, 30019, Republic of Korea.

Influenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant strains, thereby necessitating the discovery of new drugs. In this study, we found aprotinin, a serine protease inhibitor, as an anti-influenza candidate through screening of compound libraries. Read More

View Article and Full-Text PDF

Platelet Function in CKD: A Systematic Review and Meta-Analysis.

J Am Soc Nephrol 2021 May 3. Epub 2021 May 3.

Institute for Molecular Cardiovascular Research, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany

Background: Patients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings. Read More

View Article and Full-Text PDF

Long Non-Coding RNA Small Nucleolar RNA Host Gene 1 Alleviates Sepsis-Associated Myocardial Injury by Modulating the miR-181a-5p/XIAP Axis .

Ann Clin Lab Sci 2021 Mar;51(2):231-240

Department of Emergency, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China

Objective: Sepsis is a systemic inflammatory response syndrome that results in severe myocardial injury. This study aimed to explore the role and mechanism of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in sepsis-induced myocardial injury .

Methods: Embryonic rat ventricular myocardial cell line (H9c2) was treated with lipopolysaccharide (LPS) to simulate sepsis-induced myocardial injury . Read More

View Article and Full-Text PDF

Ziyuglycoside II inhibits the growth of digestive system cancer cells through multiple mechanisms.

Chin J Nat Med 2021 May;19(5):351-363

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address:

Digestive system cancers, including liver, gastric, colon, esophageal and pancreatic cancers, are the leading cause of cancers with high morbidity and mortality, and the question of their clinical treatment is still open. Previous studies have indicated that Ziyuglycoside II (ZYG II), the major bioactive ingredient extract from Sanguisorba officinalis L., significantly inhibits the growth of various cancer cells. Read More

View Article and Full-Text PDF

Establishment of an anti-inflammation-based bioassay for the quality control of the 13-component TCM formula (Lianhua Qingwen).

Pharm Biol 2021 Dec;59(1):537-545

Department of Hematology, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China.

Context: Owing to the complexity of chemical ingredients in traditional Chinese medicine (TCM), it is difficult to maintain quality and efficacy by relying only on chemical markers.

Objective: Lianhua Qingwen capsule (LHQW) was selected as an example to discuss the feasibility of a bioassay for quality control.

Materials And Methods: Network pharmacology was used to screen potential targets in LHQW with respect to its anti-inflammatory effects. Read More

View Article and Full-Text PDF
December 2021

Cytotoxicity of filtering respiratory protective devices from the waste sorting industry: A comparative study between interior layer and exhalation valve.

Environ Int 2021 Apr 30;155:106603. Epub 2021 Apr 30.

H&TRC- Health & Technology Research Center, ESTeSL- Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Portugal; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.

Filtering respiratory protection devices (FRPD) are mandatory for workers to wear in the Portuguese waste-sorting industry. Previous results regarding microbial contamination found on FRPD interior layer raised the question of whether microbial contamination from the exhalation valve would also have cytotoxicity effects. Since the FRPD exhalation valves are very close to workers' nose and mouth, they represent a source of exposure to bioburden by inhalation. Read More

View Article and Full-Text PDF

Advanced oxidation of 4-chlorophenol via combined pulsed light and sulfate radicals methods: Effect of co-existing anions.

J Environ Manage 2021 Apr 30;291:112595. Epub 2021 Apr 30.

Department of Chemistry, Karnatak University, Dharwad, 580 003, India. Electronic address:

Pulsed light (PL) technology, which is based on photonic technology involves the application of broadband emission of light with short and high-power pulses is beginning to emerge for the treatment of wastes via advanced oxidation processes (AOP). The present work investigates the efficiency of PL as a light source for persulfate (PS) activation (PL/PS) and 4-chlorophenol)4-CP) degradation, an organic model pollutant. The influencing parameters on 4-CP degradation such as solution pH, reaction time, initial concentration of 4-CP, PS dose, pulse intensity and frequency, and distance from PL source are systematically investigated. Read More

View Article and Full-Text PDF

Dual effects of quercetin on protein digestion and absorption in the digestive tract.

Food Chem 2021 Apr 20;358:129891. Epub 2021 Apr 20.

College of Chemistry, National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, Fuzhou University, Fuzhou, China; College of Biological Science and Engineering, National & Local Joint Biomedical Engineering Research Center on Photodynamic Technologies, Fuzhou University, Fuzhou, China; Fujian Key Laboratory of Marine Enzyme Engineering, Fuzhou University, Fuzhou, China. Electronic address:

Quercetin is a well-studied natural product with multiple pharmacological properties. In this study, we demonstrated that quercetin suppressed protein digestion in the intestinal fluid by inhibiting trypsin, a key digestive enzyme. However, we also observed a previously unknown property of quercetin: promoting the intestinal absorption of proteins. Read More

View Article and Full-Text PDF

GrgA overexpression inhibits Chlamydia trachomatis growth through sigma-and sigma-dependent mechanisms.

Microb Pathog 2021 Apr 30:104917. Epub 2021 Apr 30.

Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers The State University of New Jersey, Piscataway, NJ, 08854, USA. Electronic address:

The obligate intracellular bacterium Chlamydia trachomatis is an important human pathogen with a biphasic developmental cycle comprised of an infectious elementary body (EB) and a replicative reticulate body (RB). Whereas σ, the primary sigma factor, is necessary for transcription of most chlamydial genes throughout the developmental cycle, σ is required for expression of some late genes. We previously showed that the Chlamydia-specific transcription factor GrgA physically interacts with both of these sigma factors and activates transcription from σ-and σ-dependent promoters in vitro. Read More

View Article and Full-Text PDF

Phytochemical properties, biological activities and medicinal use of Centaurium erythraea Rafn.

J Ethnopharmacol 2021 Apr 30:114171. Epub 2021 Apr 30.

Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, And Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco. Electronic address:

Ethnopharmacological Relevance: Centaurium erythraea is an important medicinal plant in many countries, e.g. Morocco, Algeria, Italy, Spain, Portugal, and countries of Balkan Peninsula. Read More

View Article and Full-Text PDF

Effects of Wnt5a overexpression in spinal cord injury.

J Cell Mol Med 2021 May 3. Epub 2021 May 3.

Laboratory of Molecular Neurology, Hospital Nacional de Parapléjicos, Toledo, Spain.

Accordingly to its known function in corticospinal tract (CST) developmental growth, previous reports have shown an inhibitory role of Wnt5a in CST regeneration after spinal cord injury (SCI). Interestingly, it has been subsequently demonstrated that Wnt5a also modulates the developmental growth of non-CST axons and that different Wnt5a receptors are expressed in neurons, oligodendrocytes, NG2+ glial precursors and reactive microglia/macrophages and astrocytes after SCI. However, the role of Wnt5a in the response of these cell types, in the regeneration of non-CST axons and in functional recovery after SCI is currently unknown. Read More

View Article and Full-Text PDF

6-Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species.

J Cell Mol Med 2021 May 3. Epub 2021 May 3.

Medicinal Plants Research Center, Shahed University, Tehran, Iran.

Combination therapies, using medicinal herbs, are broadly recommended to attenuate the chemotherapy adverse effects. Based on our previous findings considering the anti-leukaemic effects of ginger extract on acute lymphoblastic leukaemia (ALL) cells, the present study was aimed to investigate the anti-cancer role of this pharmaceutical plant on ALL mice models. Moreover, we worked towards identifying the most anti-leukaemic derivative of ginger and the mechanism through which it may exert its cytotoxic impact. Read More

View Article and Full-Text PDF

Association of Local Variation in Neighborhood Disadvantage in Metropolitan Areas With Youth Neurocognition and Brain Structure.

JAMA Pediatr 2021 May 3:e210426. Epub 2021 May 3.

Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles.

Importance: Neighborhood disadvantage is an important social determinant of health in childhood and adolescence. Less is known about the association of neighborhood disadvantage with youth neurocognition and brain structure, and particularly whether associations are similar across metropolitan areas and are attributed to local differences in disadvantage.

Objective: To test whether neighborhood disadvantage is associated with youth neurocognitive performance and with global and regional measures of brain structure after adjusting for family socioeconomic status and perceptions of neighborhood characteristics, and to assess whether these associations (1) are pervasive or limited, (2) vary across metropolitan areas, and (3) are attributed to local variation in disadvantage within metropolitan areas. Read More

View Article and Full-Text PDF

Suppressive effect of tamarixetin, isolated from , on degranulation and eicosanoid production in bone marrow-derived mast cells.

Allergol Immunopathol (Madr) 2021 1;49(3):42-49. Epub 2021 May 1.

Division of Korean Medicine Development, National Development Institute of Korean Medicine, Gyeongsan, Republic of Korea;

Background: The aim of this study was to evaluate the inhibitory effect of tamarixetin on the production of inflammatory mediators in IgE/antigen-induced mouse bone marrow-derived mast cells (BMMCs).

Materials And Methods: The effects of tamarixetin on mast cell activation were investigated with regard to degranulation, eicosanoid generation, Ca2+ influx, and immunoblotting of various signaling molecules.

Results: Tamarixetin effectively decreased degranulation and the eicosanoid generation such as leukotriene C and prostaglandin D in BMMCs. Read More

View Article and Full-Text PDF

Thymoquinone reduces mitochondrial damage and death of cardiomyocytes induced by clozapine.

Naunyn Schmiedebergs Arch Pharmacol 2021 May 3. Epub 2021 May 3.

Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.

The generation of a reactive nitrenium ion by microsomal/mitochondrial cytochrome P450 (CYPs) from clozapine (CLZ) has been suggested as the main cause of cardiotoxicity by this drug. Previous studies indicated that thymoquinone (TQ) as an active constituent of Nigella sativa has pharmacological effects such as antioxidant, reactive oxygen species (ROS) scavenger, and inhibitory effect on CYPs enzymes. Therefore, we hypothesized that TQ with these pharmacological effects can reduce CLZ-induced toxicity in isolated cardiomyocytes and mitochondria. Read More

View Article and Full-Text PDF

The antibacterial effects of vitamin D3 against mutans streptococci: an in vitro study.

Eur Oral Res 2021 Jan;55(1):8-15

Faculty of Dentistry, Universiti Teknologi MARA,Selangor,Malaysia.

Purpose: This study aims to evaluate the antimicrobial effects of the cholecalciferol vitamin D3 against Streptococcus sobrinus (Strep. sobrinus) and Streptococcus mutans (Strep. mutans) bacteria in vitro that is considered the main causative bacteria in dental caries development. Read More

View Article and Full-Text PDF
January 2021