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Total 12097 results found since Jan 2013.

PCSK9 inhibition in the management of familial hypercholesterolemia.
Abstract Familial hypercholesterolemia (FH) is a frequent hereditary metabolic disease characterized by high serum low-density lipoprotein (LDL) cholesterol concentration and premature atherosclerotic cardiovascular disease (ASCVD). The discovery of the LDL receptor as one of the causative genes of FH enabled us to understand the pathophysiology of FH and paved the way for developing statins. Similar to LDL receptor, discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) also created an opportunity for developing its inhibitors. Since PCSK9 degrades LDL receptor protein, inhibiting PCSK9 will be an eff...
Source: Journal of Cardiology - August 4, 2017 Category: Cardiology Authors: Ogura M Tags: J Cardiol Source Type: research

OPN b and c Isoforms Doubtless Veto Anti-angiogenesis Effects of Curcumin in Combination with Conventional AML Regiment
Authors: Mirzaei A, Ghaffari SH, Nikbakht M, Kamranzadeh Foumani H, Vaezi M, Mohammadi S, Alimoghaddam K, Ghavamzadeh A Abstract Osteopontin (OPN) is an extracellular structural protein that is secreted by osteoblasts and hematopoietic cells. It suppresses the proliferation of hematopoietic stem and also plays an important role in promoting survival and drug resistance in leukemic stem cells (LSCs). Since the role of OPN isoforms in AML angiogenesis are remaining controversial, in the present study, we aimed to evaluate whether curcumin (CUR), as a known natural component with anti-angiogenesis effects, in a combin...
Source: Asian Pacific Journal of Cancer Prevention - September 29, 2017 Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research

Identification of Estrogen-Related Receptor Alpha Agonists in the Tox21 Compound Library.
This study is the first comprehensive analysis in discovering potential endocrine disrupters which affect the ERRα signaling pathway. PMID: 29216352 [PubMed - as supplied by publisher]
Source: Endocrinology - December 4, 2017 Category: Endocrinology Authors: Lynch C, Zhao J, Huang R, Kanaya N, Bernal L, Hsieh JH, Auerbach SS, Witt KL, Merrick BA, Chen S, Teng CT, Xia M Tags: Endocrinology Source Type: research

Fight Aging! Newsletter, April 16th 2018
This study demonstrates that small peptide domains derived from native protein amelogenin can be utilized to construct a mineral layer on damaged human enamel in vitro. Six groups were prepared to carry out remineralization on artificially created lesions on enamel: (1) no treatment, (2) Ca2+ and PO43- only, (3) 1100 ppm fluoride (F), (4) 20 000 ppm F, (5) 1100 ppm F and peptide, and (6) peptide alone. While the 1100 ppm F sample (indicative of common F content of toothpaste for homecare) did not deliver F to the thinly deposited mineral layer, high F test sample (indicative of clinical varnish treatment) formed mainly C...
Source: Fight Aging! - April 15, 2018 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

PCSK9 Inhibitors: Novel Therapeutic Strategies for Lowering LDL-Cholesterol.
Abstract Statins are currently the major therapeutic strategies to lower low-density lipoprotein cholesterol (LDL-C) levels. However, a number of hypercholesterolemia patients still have a residual cardiovascular disease (CVD) risk despite taking the maximum-tolerated dose of statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptor (LDLR), inducing its degradation in the lysosome and inhibiting LDLR recirculating to the cell membranes. The gain-of-function mutations in PCSK9 elevate the LDL-C levels in plasma. Therefore, PCSK9 inhibitors become novel therapeutic appr...
Source: Mini Reviews in Medicinal Chemistry - April 22, 2018 Category: Chemistry Authors: Liu ZP, Wang Y Tags: Mini Rev Med Chem Source Type: research

PCSK9 inhibitors and LDL reduction: pharmacology, clinical implications and future perspectives.
Authors: Fitzgerald G, Kiernan T Abstract INTRODUCTION: PCSK9 inhibitors are monoclonal antibodies to proprotein convertase-subtilisin/kexin type 9 which significantly reduce LDL cholesterol concentration in vivo by inhibiting degradation of the LDL receptor in hepatocytes. The introduction of PCSK9 inhibitors heralded a new era of intensive LDL-C reduction with LDL-C concentrations lowered below levels ever thought possible with conventional treatments such as statins. With their introduction considerations regarding cost, clinical outcomes and long-term safety are paramount. Areas covered: This review examines th...
Source: Expert Review of Cardiovascular Therapy - July 8, 2018 Category: Cardiology Tags: Expert Rev Cardiovasc Ther Source Type: research

ASAP pH-Sensitive Nanocarrier-Mediated Codelivery of Simvastatin and Noggin siRNA for Synergistic Enhancement of Osteogenesis
ACS Applied Materials& InterfacesDOI: 10.1021/acsami.8b10521
Source: ACS Applied Materials and Interfaces - August 16, 2018 Category: Materials Science Authors: Jinsheng Huang, Chaowen Lin, Jintao Fang, Xiaoxia Li, Jin Wang, Shaohui Deng, Sheng Zhang, Wanhan Su, Xiaoreng Feng, Bin Chen, Du Cheng, Xintao Shuai Source Type: research

Fight Aging! Newsletter, December 17th 2018
In this study, we found that TNF-α resulted in an impairment of autophagic flux in microglia. Concomitantly, an increase of M1 marker expression and reduction of M2 marker expression were observed in TNF-α challenged microglia. Upregulation of autophagy via serum deprivation or pharmacologic activators (rapamycin and resveratrol) promoted microglia polarization toward M2 phenotype, as evidenced by suppressed M1 and elevated M2 gene expression, while inhibition of autophagy with 3-MA or Atg5 siRNA consistently aggravated the M1 polarization induced by TNF-α. Moreover, Atg5 knockdown alone was sufficient to trigger...
Source: Fight Aging! - December 16, 2018 Category: Research Authors: Reason Tags: Newsletters Source Type: blogs

Lovastatin attenuates angiotensin II induced cardiovascular fibrosis through the suppression of YAP/TAZ signaling.
Abstract Angiotensin II (ANG II) is associated with fibrosis in both clinical and basic studies. Thus, we aimed to explore a mechanism by which ANG II induces fibrosis. 5 μM of ANG II was used in the in vitro study. The mouse cardiovascular fibrosis model was established by infused with AngII (1000 ng/kg/min) for 7 days and cotreated with lovastatin (10 mg/kg daily) or vehicle control (DMSO in saline). We found that ANG II activated yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), two transcription factors that were shown to induce fibrosis. Inhibition of ras homol...
Source: Biochemical and Biophysical Research communications - March 25, 2019 Category: Biochemistry Authors: Wu P, Liu Z, Zhao T, Xia F, Gong L, Zheng Z, Chen Z, Yang T, Duan Q Tags: Biochem Biophys Res Commun Source Type: research

Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

LRP6 mediated signal transduction pathway triggered by tissue plasminogen activator acts through lipid rafts in neuroblastoma cells.
Abstract LDL receptor-related proteins 6 (LRP6) is a type I transmembrane receptor (C-terminus in cytosol), which appears to be essential in numerous biological processes, since it is an essential co-receptor of Wnt ligands for canonical β-catenin dependent signal transduction. It was shown that tissue plasminogen activator (tPA), physically interacting with LRP6, induces protein phosphorylation, which may have large implication in the regulation of neural processes. In this investigation we analyzed whether LRP6 is associated with lipid rafts following tPA triggering in neuroblastoma cells and the role of raft i...
Source: Journal of Cell Communication and Signaling - February 14, 2020 Category: Molecular Biology Authors: Riitano G, Manganelli V, Capozzi A, Mattei V, Recalchi S, Martellucci S, Longo A, Misasi R, Garofalo T, Sorice M Tags: J Cell Commun Signal Source Type: research

Berberine Promotes OATP1B1 Expression and Rosuvastatin Uptake by Inducing Nuclear Translocation of FXR and LXR α
In conclusion, berberine-induced nuclear translocation of FXR and LXRα could activate OATP1B1 promoter, resulting in enhanced expression of OATP1B1 and increased uptake of rosuvastatin.
Source: Frontiers in Pharmacology - March 26, 2020 Category: Drugs & Pharmacology Source Type: research

Simvastatin Suppresses Human Breast Cancer Cell Invasion by Decreasing the Expression of Pituitary Tumor-Transforming Gene 1
Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been widely used to lower cholesterol and prevent cardiovascular diseases. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer, while the underlying mechanisms remain to be elucidated. Herein, we sought to investigate the effect of statins on the expression of pituitary tumor-transforming gene 1 (PTTG1), a critical gene involved in human breast cancer invasion and metastasis. Our results showed that PTTG1 is highly expressed in malignant Hs578T and MDA-MB-231 breast cancer cel...
Source: Frontiers in Pharmacology - November 4, 2020 Category: Drugs & Pharmacology Source Type: research

New Trends in Dyslipidemia Treatment.
Abstract Dyslipidemia is one of the most important risk factors for cardiovascular (CV) disease. Statin therapy has dramatically improved CV outcomes and is the backbone of current lipid-lowering therapy, but despite well-controlled low-density lipoprotein cholesterol (LDL-C) levels through statin administration, up to 40% patients still experience CV disease. New therapeutic agents to tackle such residual cholesterol risk by lowering not only LDL-C but triglycerides (TG), TG-rich lipoproteins (TRL), or lipoprotein(a) (Lp(a)) are being introduced. Ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) mo...
Source: Circulation Journal - November 12, 2020 Category: Cardiology Authors: Jang AY, Lim S, Jo SH, Han SH, Koh KK Tags: Circ J Source Type: research

Cholesterol synthesis inhibition promotes axonal regeneration in the injured central nervous system.
Abstract Neuronal regeneration in the injured central nervous system is hampered by multiple extracellular proteins. These proteins exert their inhibitory action through interactions with receptors that are located in cholesterol rich compartments of the membrane termed lipid rafts. Here we show that cholesterol-synthesis inhibition prevents the association of the Neogenin receptor with lipid rafts. Furthermore, we show that cholesterol-synthesis inhibition enhances axonal growth both on inhibitory -myelin and -RGMa substrates. Following optic nerve injury, lowering cholesterol synthesis with both drugs and siRNA-...
Source: Neurobiology of Disease - January 9, 2021 Category: Neurology Authors: Shabanzadeh AP, Charish J, Tassew NG, Farhani N, Feng J, Qin X, Sugita S, Mothe AJ, Wälchli T, Koeberle PD, Monnier PP Tags: Neurobiol Dis Source Type: research