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Valdecoxib improves lipid-induced skeletal muscle insulin resistance via simultaneous suppression of inflammation and endoplasmic reticulum stress.

Biochem Pharmacol 2021 Apr 9:114557. Epub 2021 Apr 9.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. Electronic address:

Valdecoxib (VAL), a non-steroidal anti-inflammatory drug, has been widely used for treatment of rheumatoid arthritis, osteoarthritis, and menstrual pain. It is a selective cyclooxygenase-2 inhibitor. The suppressive effects of VAL on cardiovascular diseases and neuroinflammation have been documented; however, its impact on insulin signaling in skeletal muscle has not been studied in detail. Read More

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The High Affinity Dopamine D Receptor Agonist MCL-536: A New Tool for Studying Dopaminergic Contribution to Neurological Disorders.

ACS Chem Neurosci 2021 Apr 12. Epub 2021 Apr 12.

Division of Basic Neuroscience, Medicinal Chemistry Laboratory, McLean Hospital, Belmont, Massachusetts 02478, United States.

The dopamine D receptor exists in two different states, D and D; the former is the functional form of the D receptor and associates with intracellular G-proteins. The D agonist [H]MCL-536 has high affinity for the D receptor ( 0.8 nM) and potently displaces the binding of (-(-)---propylnorapomorphine (NPA; 0. Read More

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LncRNA MEG3 Alleviates Diabetic Cognitive Impairments by Reducing Mitochondrial-Derived Apoptosis through Promotion of FUNDC1-Related Mitophagy via Rac1-ROS Axis.

ACS Chem Neurosci 2021 Apr 12. Epub 2021 Apr 12.

Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410078, Hunan, China.

Mitochondrial dysfunction and elevated ROS generation are predominant contributors of neuronal death that is responsible for the diabetes-related cognitive impairments. Emerging evidence has demonstrated that long noncoding RNA-MEG3 can serve as an important regulator in the pathogenesis of diabetes. However, the underlying mechanisms remain to be further clarified. Read More

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Epigallocathechin--3-Gallate Inhibits Trypanothione Reductase of , Causing Alterations in Redox Balance and Leading to Parasite Death.

Front Cell Infect Microbiol 2021 25;11:640561. Epub 2021 Mar 25.

Laboratório de Bioquímica de Tripanosomatideos, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Brazil.

is a protozoan parasite that causes a vector borne infectious disease in humans known as visceral leishmaniasis (VL). This pathology, also caused by , presently impacts the health of 500,000 people worldwide, and is treated with outdated anti-parasitic drugs that suffer from poor treatment regimens, severe side effects, high cost and/or emergence of resistant parasites. In previous works we have disclosed the anti- activity of (-)-Epigallocatechin 3--gallate (EGCG), a flavonoid compound present in green tea leaves. Read More

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A proline-rich motif in the large intracellular loop of the glycine receptor α1 subunit interacts with the Pleckstrin homology domain of collybistin.

J Adv Res 2021 Mar 8;29:95-106. Epub 2020 Oct 8.

Department of Biochemistry, German University in Cairo, Egypt.

Introduction: The inhibitory glycine receptor (GlyR), a mediator of fast synaptic inhibition, is located and held at neuronal synapses through the anchoring proteins gephyrin and collybistin. Stable localization of neurotransmitter receptors is essential for synaptic function. In case of GlyRs, only beta subunits were known until now to mediate synaptic anchoring. Read More

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Febuxostat mitigates IL-18-induced inflammatory response and reduction of extracellular matrix gene.

Am J Transl Res 2021 15;13(3):979-987. Epub 2021 Mar 15.

Department of Rheumatology, Shandong Zibo Central Hospital Zibo 255036, Shandong, China.

Background: Osteoarthritis (OA) is a disease commonly diagnosed in the elderly population. It is reported that the reduction of extracellular matrix and infiltrated inflammation are two main factors responsible for the pathogenesis of OA. This investigation aims to explore the potential protective effects of Febuxostat against IL-18-induced insults in chondrocytes, as well as the possible mechanism. Read More

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Bone marrow mesenchymal stem cells-secreted exosomal H19 modulates lipopolysaccharides-stimulated microglial M1/M2 polarization and alleviates inflammation-mediated neurotoxicity.

Am J Transl Res 2021 15;13(3):935-951. Epub 2021 Mar 15.

Department of Obstetrics, Shandong Provincial Maternal and Child Health Care Hospital, Cheeloo College of Medicine, Shandong University Ji'nan 250014, Shandong, China.

Neuroinflammation is the most common cause of neurological diseases. Exosomes derived from mesenchymal stem cells (MSCs-exos) have been reported to reduce inflammation and neuronal injury. Its underlying mechanism remains poorly unknown. Read More

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Intracellular Progesterone Receptor and cSrc Protein Working Together to Regulate the Activity of Proteins Involved in Migration and Invasion of Human Glioblastoma Cells.

Front Endocrinol (Lausanne) 2021 26;12:640298. Epub 2021 Mar 26.

Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, Mexico.

Glioblastomas are the most common and aggressive primary brain tumors in adults, and patients with glioblastoma have a median survival of 15 months. Some alternative therapies, such as Src family kinase inhibitors, have failed presumably because other signaling pathways compensate for their effects. In the last ten years, it has been proven that sex hormones such as progesterone (P4) can induce growth, migration, and invasion of glioblastoma cells through its intracellular progesterone receptor (PR), which is mostly known for its role as a transcription factor, but it can also induce non-genomic actions. Read More

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GYY4137 and Sodium Hydrogen Sulfide Relaxations Are Inhibited by L-Cysteine and K7 Channel Blockers in Rat Small Mesenteric Arteries.

Front Pharmacol 2021 26;12:613989. Epub 2021 Mar 26.

Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark.

Donors of HS may be beneficial in treating cardiovascular diseases where the plasma levels of HS are decreased. Therefore, we investigated the mechanisms involved in relaxation of small arteries induced by GYY4137 [(4-methoxyphenyl)-morpholin-4-yl-sulfanylidene-sulfido-λ5-phosphane;morpholin-4-ium], which is considered a slow-releasing HS donor. Sulfides were measured by use of 5,5'-dithiobis-(2-nitro benzoic acid), and small rat mesenteric arteries with internal diameters of 200-250 µm were mounted in microvascular myographs for isometric tension recordings. Read More

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Korean Red ginseng prevents endothelial senescence by downregulating the HO-1/NF-κB/miRNA-155-5p/eNOS pathway.

J Ginseng Res 2021 Mar 14;45(2):344-353. Epub 2020 Aug 14.

Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 24341, South Korea.

Background: Korean Red ginseng extract (KRGE) has beneficial effects on the cardiovascular system by improving endothelial cell function. However, its pharmacological effect on endothelial cell senescence has not been clearly elucidated. Therefore, we examined the effect and molecular mechanism of KRGE on the senescence of human umbilical vein endothelial cells (HUVECs). Read More

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Complement receptor 3 mediates both sinking phagocytosis and phagocytic cup formation via distinct mechanisms.

J Biol Chem 2021 Jan 8;296:100256. Epub 2021 Jan 8.

Institut für Molekulare Zellbiologie, Westfälische Wilhems-Universität Münster, Münster, Germany; Department of Physiology, Pathophysiology and Toxicology and ZBAF (Centre for Biomedical Education and Research), Faculty of Health, School of Medicine, Witten/Herdecke University, Witten, Germany. Electronic address:

A long-standing hypothesis is that complement receptors (CRs), especially CR3, mediate sinking phagocytosis, but evidence is lacking. Alternatively, CRs have been reported to induce membrane ruffles or phagocytic cups, akin to those induced by Fcγ receptors (FcγRs), but the details of these events are unclear. Here we used real-time 3D imaging and KO mouse models to clarify how particles (human red blood cells) are internalized by resident peritoneal F4/80 cells (macrophages) via CRs and/or FcγRs. Read More

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January 2021

Trop-2 cleavage by ADAM10 is an activator switch for cancer growth and metastasis.

Neoplasia 2021 Apr 8;23(4):415-428. Epub 2021 Apr 8.

Unit of Medical Genetics, Department of Biomedical Sciences (BIOMORF), University of Messina, Italy. Electronic address:

Trop-2 is a transmembrane signal transducer that can induce cancer growth. Using antibody targeting and N-terminal Edman degradation, we show here that Trop-2 undergoes cleavage in the first thyroglobulin domain loop of its extracellular region, between residues R87 and T88. Molecular modeling indicated that this cleavage induces a profound rearrangement of the Trop-2 structure, which suggested a deep impact on its biological function. Read More

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Silencing long non-coding RNA MEG8 inhibits the proliferation and induces the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis.

Biochem Biophys Res Commun 2021 Apr 8;556:72-78. Epub 2021 Apr 8.

The First People's Hospital of Yunnan Province, Kunming, 650032, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China. Electronic address:

Even though long non-coding RNA (lncRNA) MEG8 plays vital roles in carcinogenesis of malignances, its roles and mechanisms in hemangioma remain unknown. Therefore, we evaluate the oncogenic roles of MEG8 in hemangioma. Small interfering RNA (siRNA)-mediated depletion of MEG8 inhibited the proliferation and increased MDA level in human hemangioma endothelial cells (HemECs). Read More

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Glucocorticoids suppressed osteoblast differentiation by decreasing Sema3A expression via the PIK3/Akt pathway.

Exp Cell Res 2021 Apr 7:112595. Epub 2021 Apr 7.

Department of Operative Dentistry and Endodontics, Guanghua School and Hospital of Stomatology & Institute of Stomatological Research, Sun Yat-sen University, 510055,Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China. Electronic address:

Glucocorticoids(GCs) are extensively used to treat inflammatory and autoimmune diseases. Excessive prolonged exposure to glucocorticoids is associated with an increased risk of osteoporosis. The inhibition of osteoblast differentiation by GCs is suggested as a major cause for GCs-induced osteoporosis (GIO). Read More

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CCR8 marks highly suppressive Treg cells within tumours but is dispensable for their accumulation and suppressive function.

Immunology 2021 Apr 10. Epub 2021 Apr 10.

Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP, Cambridge, UK.

CD4 regulatory T (Treg) cells, dependent upon the transcription factor Foxp3, contribute to tumour immunosuppression but are also required for immune homeostasis. There is interest in developing therapies that selectively target the immunosuppressive function of Treg cells within tumours without disrupting their systemic anti-inflammatory function. High levels of expression of Chemokine (C-C motif) receptor 8 (CCR8) discriminate Treg cells within tumours from those found in systemic lymphoid tissues. Read More

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The relationship between fasting-induced torpor, sleep and waking in laboratory mice.

Sleep 2021 Apr 10. Epub 2021 Apr 10.

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.

Study Objectives: Torpor is a regulated and reversible state of metabolic suppression used by many mammalian species to conserve energy. Whereas the relationship between torpor and sleep has been well-studied in seasonal hibernators, less is known about the effects of fasting-induced torpor on states of vigilance and brain activity in laboratory mice.

Methods: Continuous monitoring of electroencephalogram (EEG), electromyogram (EMG) and surface body temperature was undertaken in adult, male C57BL/6 mice over consecutive days of scheduled restricted feeding. Read More

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Dicer represses the interferon response and the double-stranded RNA-activated protein kinase pathway in mouse embryonic stem cells.

J Biol Chem 2021 Jan 8;296:100264. Epub 2021 Jan 8.

Department of Cell and Molecular Biology, The University of Southern Mississippi, Hattiesburg, Mississippi, USA. Electronic address:

Recent studies have demonstrated that embryonic stem cells (ESCs) are deficient in expressing type I interferons (IFN), the cytokines that play key roles in antiviral responses. However, the underlying molecular mechanisms and biological implications of this finding are poorly understood. In this study, we developed a synthetic RNA-based assay that can simultaneously assess multiple forms of antiviral responses. Read More

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January 2021

Zinc transporter mutations linked to acrodermatitis enteropathica disrupt function and cause mistrafficking.

J Biol Chem 2021 Jan 8;296:100269. Epub 2021 Jan 8.

Department of Chemistry, Michigan State University, East Lansing, Michigan, USA; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA. Electronic address:

ZIP4 is a representative member of the Zrt-/Irt-like protein (ZIP) transporter family and responsible for zinc uptake from diet. Loss-of-function mutations of human ZIP4 (hZIP4) drastically reduce zinc absorption, causing a life-threatening autosomal recessive disorder, acrodermatitis enteropathica (AE). These mutations occur not only in the conserved transmembrane zinc transport machinery, but also in the extracellular domain (ECD) of hZIP4, which is only present in a fraction of mammalian ZIPs. Read More

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January 2021

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J Pharmacol Exp Ther 2021 Apr 9. Epub 2021 Apr 9.

Takeda Development Center Japan, Takeda Pharmaceutical Company Ltd., Japan.

Under healthy condition, more than one urethra-closing reflex, including both bladder afferent-independent and -dependent actions function during momentary elevation of intravesical (bladder) pressure to prevent urinary incontinence In the current study, the effects of a novel selective 5-hydroxytryptamine type 2C (5-HT) receptor agonist, TAK-233, on evoked momentary urethra-closing functions were investigated in female rats and humans to elucidate 5-HT receptor functions. In anesthetized female rats, TAK-233 dose-dependently and significantly increased the urethral resistance during sneezing in rats with distended vaginas and bilaterally transected pelvic nerves. The drug also dose-dependently and significantly increased urethral resistance during momentary intravesical pressure elevation by electrical stimulation of abdominal muscles in rats with a transected spinal cord at the T8-9 level and intact pelvic nerves. Read More

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Characterization of a lysozyme-like effector TseP and secretion co-dependence of the type VI secretion system in SSU.

Appl Environ Microbiol 2021 Apr 9. Epub 2021 Apr 9.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China

The type VI secretion system (T6SS) is a widespread weapon employed by gram-negative bacteria for interspecies interaction in complex communities. Analogous to a contractile phage tail, the double-tubular T6SS injects toxic effectors into prokaryotic and eukaryotic neighboring cells. Although effectors dictate T6SS functions, their identities remain elusive in many pathogens. Read More

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LncRNA small nucleolar RNA host gene 16 (SNHG16) silencing protects lipopolysaccharide (LPS)-induced cell injury in human lung fibroblasts WI-38 through acting as miR-141-3p sponge.

Biosci Biotechnol Biochem 2021 Feb 1. Epub 2021 Feb 1.

Department of oral and maxillofacial surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong, China.

Long noncoding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) is correlated with cell injuries, including pneumonia. However, its role and mechanism remain vague in pneumonia. The interplay among genes was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. Read More

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February 2021

1-Ethyl-β-N-acetylglucosaminide increases hyaluronan production in human keratinocytes by being converted to N-acetylglucosamine via β-N-acetylglucosaminidase-dependent manner.

Biosci Biotechnol Biochem 2021 Apr 9. Epub 2021 Apr 9.

Biological Science Research, Kao Corporation; 5-3-28 Kotobuki-cho, Odawara-shi, Kanagawa 250-0002, Japan.

Regulation of hyaluronan (HA) is important for the maintenance of epidermal homeostasis. Here we examined the mechanism by which 1-ethyl-β-N-acetylglucosaminide (β-NAG2), a newly developed N-acetylglucosamine (NAG) derivative, increases HA production in cultured human epidermal keratinocytes. When keratinocytes were treated with β-NAG2, mRNA expression of HA synthase 3, which is responsible for HA production in human keratinocytes, was not influenced, but the intracellular level of UDP-NAG, a substrate used for HA synthesis, was increased. Read More

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The Effect of Schooling on Women's Overweight and Obesity: A Natural Experiment in Nigeria.

Authors:
Pepita Barlow

Demography 2021 Apr;58(2):685-710

Department of Health Policy, London School of Economics and Political Science, London, UK.

An extensive social scientific literature has documented the importance of schooling in preventing overweight and obesity among women. However, prior quasi-experimental studies investigating the causal effect of schooling on women's overweight and obesity have focused almost exclusively on high-income countries (HICs). Schooling effects may differ in low- or middle-income countries (LMICs), where information about the harms of being overweight is often sparse and where larger body sizes can be socially valued. Read More

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Resveratrol Derivative, Trans-3, 5, 4'-Trimethoxystilbene Sensitizes Osteosarcoma Cells to Apoptosis via ROS-Induced Caspases Activation.

Oxid Med Cell Longev 2021 25;2021:8840692. Epub 2021 Mar 25.

Institute of Advanced Diagnostic and Clinical Medicine, Zhongshan People's Hospital, Guangzhou University & Zhongshan People's Hospital Joint Biomedical Institute, 2 Sun Wen East Road, Zhongshan, Guangdong 528400, China.

Numerous studies have shown that resveratrol can induce apoptosis in cancer cells. Trans-3, 5, 4'-trimethoxystilbene (TMS), a novel derivative of resveratrol, is a more potent anticancer compound than resveratrol and can induce apoptosis in cancer cells. Herein, we examined the mechanisms involved in TMS-mediated sensitization of human osteosarcoma (143B) cells to TNF-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis. Read More

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Resveratrol Alleviates Vascular Endothelial Damage Caused by Lower-Extremity Ischemia Reperfusion (I/R) through Regulating Keap1/Nrf2 Signaling-Mediated Oxidative Stress.

Evid Based Complement Alternat Med 2021 24;2021:5556603. Epub 2021 Mar 24.

Department of Vascular Surgery, Peking Union Medical College Hospital, Beijing 100730, China.

The present study aims to investigate the protective effects of Resveratrol (RSV) against vascular endothelial damage caused by lower-extremity I/R and the underlying preliminary mechanism. The in vitro hypoxia reoxygenation (HR) model was established on HUVECs. Lower-extremity I/R model was established on rats followed by being treated with RSV and the pathological state of artery was evaluated by HE and EVG staining, while the apoptotic state of artery was detected by TUNEL assay. Read More

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COX-2 promotes the osteogenic potential of BMP9 through TGF-β1/p38 signaling in mesenchymal stem cells.

Aging (Albany NY) 2021 Apr 4;13. Epub 2021 Apr 4.

Department of Orthopedics, Children Hospital of Chongqing Medical University, Chongqing 400014, China.

This study investigated the effects of transforming growth factor-β1 (TGF-β1) and cyclooxygenase-2 (COX-2) on bone morphogenetic protein 9 (BMP9) in mesenchymal stem cells (MSCs). We found that BMP9 increased mRNA levels of TGF-β1 and COX-2 in C3H10T1/2 cells. BMP9-induced osteogenic markers were enhanced by TGF-β1 and reduced by TGF-βRI-specific inhibitor LY364947. Read More

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Cyclin A2/cyclin-dependent kinase 1-dependent phosphorylation of Top2a is required for S phase entry during retinal development in zebrafish.

J Genet Genomics 2021 Feb 9. Epub 2021 Feb 9.

Department of Clinical Laboratory Medicine of Shanghai Tenth People's Hospital, Tongji University School of Life Sciences and Technology, Shanghai 200092, China. Electronic address:

Cyclin-dependent kinase 1 (CDK1) plays an essential role in cell cycle regulation. However, as mouse Cdk1 embryos die early, the role of CDK1 in regulating the cell cycle and embryo development remains unclear. Here, we showed that zebrafish cdk1 embryos exhibit severe microphthalmia accompanied by multiple defects in S phase entry, M phase progression, and cell differentiation but not in interkinetic nuclear migration. Read More

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February 2021

The phospholipase D inhibitor FIPI potently blocks EGF-induced calcium signaling in human breast cancer cells.

Cell Commun Signal 2021 Apr 8;19(1):43. Epub 2021 Apr 8.

Institute of Immunology, Center of Biomedical Education and Research (ZBAF), Witten/Herdecke University, Witten, Germany.

Background: Phosphotyrosine kinase (PTK)-mediated phospholipase C-γ1 (PLC-γ1) signaling plays a crucial role in the release of the universal second messenger calcium from intracellular stores, which is mandatory for several cellular processes, including cell migration. However, PLC-γ1 could also be activated in a PTK-independent manner by phospholipase D (PLD)-derived phosphatidic acid (PA). Because both higher PLD expression levels and PLD activity have also been associated with breast cancer cell invasion and migration, we wondered whether there might be a link between PLD and PLC-γ1, which was investigated in this study. Read More

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In vitro and in vivo relaxation and anti-inflammation of Natural Flavonoids from Elaeagnus pungens leaf via L-type Calcium channel and Targeting MAPK signal pathway.

J Ethnopharmacol 2021 Apr 5:114071. Epub 2021 Apr 5.

School of Pharmaceutical Science, South-Central University for Nationalities, Wuhan, 430074, P.R. China. Electronic address:

Ethnopharmacological Relevance: In traditional Chinese medicine (TCM), the leaf of Elaeagnus pungens Thunb. (Family Elaeagnaceae) is an herb documented as an antiasthmatic remedy to treat the severe asthma, bronchitis and other respiratory diseases in the early material medica "Bencao Gangmu" (Ming dynasty, about 442 years ago).

Aim Of The Study: This work is purposed to investigate the pharmacological effects and mechanism of total flavonoids from Elaeagnus pungens leaves (FLA) on asthma in vivo and vitro. Read More

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Serum 25-hydroxyvitamin D, cardiovascular risk markers, and incident cardiovascular disease in a high risk community population.

Clin Biochem 2021 Apr 5. Epub 2021 Apr 5.

Department of Pathology and Laboratory Medicine, Cumming School of Medicine, Health Sciences Centre, Foothills Campus, University of Calgary, 3030 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada; Alberta Precision Laboratories, Diagnostic and Scientific Research Centre, #9 3535 Research Way NW, Calgary, AB, T2L 2K8, Canada; Department of Cardiac Sciences, Cumming School of Medicine, Health Sciences Centre, Foothills Campus, University of Calgary, 3030 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. Electronic address:

Background: It is unclear whether vitamin D status is related to cardiovascular risk beyond that explained by conventional risk markers. We examined the relationship between serum 25-hydroxy (OH) vitamin D and incident cardiovascular disease (CVD; heart attack/stroke) after adjusting for individual- and community-level covariates from laboratory and administrative data.

Methods: Patients receiving their first 25-OH vitamin D test in Calgary, Alberta from 2009-2013 without a past CVD diagnosis but an electrocardiogram and body mass index (BMI) +/- 3 months from testing were included. Read More

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