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Total 117 results found since Jan 2013.

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

Chemical Approaches for RNAi Drug Development.
This article focuses on our two original approaches. The first involves the groove modification of siRNA duplexes to understand siRNA-protein interactions using 7-bromo-7-deazaadenosine and 3-bromo-3-deazaadenosine as chemical probes, while the second involves the generation of RNAi medicine using chemically modified DNA, known as an intelligent shRNA expression device (iRed). PMID: 32999205 [PubMed - in process]
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 2, 2020 Category: Drugs & Pharmacology Authors: Saito-Tarashima N Tags: Yakugaku Zasshi Source Type: research

β-Estradiol Enhanced Secretion of Lipoprotein Lipase from Mouse Mammary Tumor FM3A Cells.
Abstract The role of β-estradiol (E2) in lipoprotein metabolism in mammary tumors is unclear, therefore, we investigated the effect of E2 on the secretion of lipoprotein lipase (LPL) from mouse mammary tumor FM3A cells. E2-treated cells increased the secretion of active LPL from FM3A cells in a time- and dose-dependent manner. Activity of mitogen-activated protein kinase (MAPK) was increased in the tumor cells treated with E2, and enhanced secretion of LPL was suppressed by MAPK kinase 1/2 inhibitor, PD98059, extracellular signal-regulated kinase (ERK) 1/2 inhibitor, FR180204, p38 MAPK inhibitor, SB202190, and ph...
Source: Biological and Pharmaceutical Bulletin - September 5, 2020 Category: Drugs & Pharmacology Authors: Fujii T, Ogasawara M, Kamishikiryo J, Morita T Tags: Biol Pharm Bull Source Type: research

Sinomenine inhibited Interleukin-1 β-induced matrix metalloproteinases levels via SOCS3 up-regulation in SW1353 cells.
Sinomenine inhibited Interleukin-1β-induced matrix metalloproteinases levels via SOCS3 up-regulation in SW1353 cells. Biol Pharm Bull. 2020 Sep 02;: Authors: Qi W, Gu Y, Wang Z, Fan W Abstract Matrix metalloproteinases (MMPs) are required for collagen degradation which play a key pathological role in arthritis progression. Herein, the effect of sinomenine (SN) on Interleukin 1 beta (IL-1β)-induced MMPs production and its underlying mechanism were explored in SW1353 cells. The MTT assay showed that 200 and 400 µM SN significantly inhibited SW1353 cell proliferation, thus the lower dose of SN (25-100...
Source: Biological and Pharmaceutical Bulletin - September 1, 2020 Category: Drugs & Pharmacology Authors: Qi W, Gu Y, Wang Z, Fan W Tags: Biol Pharm Bull Source Type: research

Single Dose Pharmacokinetics and Pharmacodynamics of Transthyretin Targeting GalNAc-siRNA Conjugate, Vutrisiran, in Healthy Subjects.
Abstract Vutrisiran (ALN-TTRsc02) is a liver-directed, investigational, small interfering ribonucleic acid drug for the treatment of transthyretin (TTR)-mediated amyloidosis. This Phase 1, randomized, single-blind, placebo-controlled, single ascending dose study evaluated the pharmacodynamics, pharmacokinetics, and safety profile of subcutaneously-administered vutrisiran (5-300 mg) in healthy subjects (n = 80). Vutrisiran treatment achieved potent and sustained TTR reduction in a dose-dependent manner, with mean maximum TTR reduction of 57-97%, maintained for ≥90 days post-dose. Vutrisiran was rapidly absorbed (...
Source: Clinical Pharmacology and Therapeutics - June 28, 2020 Category: Drugs & Pharmacology Authors: Habtemariam BA, Karsten V, Attarwala H, Goel V, Melch M, Clausen VA, Garg P, Vaishnaw AK, Sweetser MT, Robbie GJ, Vest J Tags: Clin Pharmacol Ther Source Type: research

Drug Delivery to Various Body Organs via Non-blood Circulatory Pathway.
Abstract Delivery of nucleic acid therapeutics to target body organs requires injection of nanocarriers into the bloodstream. However, as such nanocarriers would also be delivered to non-target organs, low delivery efficiency to target organs and risk of unexpected effects are clear limitations of this technology. We recently applied iontophoresis (IP) for direct delivery of nucleic acid therapeutics to various organs. IP relies on a weak electric current for noninvasive transdermal drug delivery. We found that IP can deliver hydrophilic macromolecules and nanoparticles into the skin. We previously succeeded in tr...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2020 Category: Drugs & Pharmacology Authors: Kogure K, Fukuta T Tags: Yakugaku Zasshi Source Type: research

Rikkunshito attenuates induction of epithelial-mesenchymal switch via activation of Sirtuin1 in ovarian cancer cells.
Authors: Kanda R, Miyagawa Y, Wada-Hiraike O, Hiraike H, Fukui S, Nagasaka K, Ryo E, Fujii T, Osuga Y, Ayabe T Abstract Rikkunshito, a traditional Japanese herbal medicine, improves appetite via activation of gastrointestinal hormone ghrelin pathway. The function of ghrelin is mediated by growth hormone secretagogue receptor (GHSR1a), and ghrelin has been known to possess diverse physiological functions including growth suppression of some cancer cells. Considering that increased ghrelin signaling by Rikkunshito could enhance sirtuin1 (SIRT1) activity in nervous system, we aimed to investigate the effect of Rikkuns...
Source: Endocrine Journal - December 18, 2019 Category: Endocrinology Tags: Endocr J Source Type: research

Development of siRNA Delivery Targeting the Tumor Microenvironment with a New Functional Device.
In conclusion, I succeeded in developing a new therapy based on regulation of the tumor microenvironment. PMID: 31685731 [PubMed - in process]
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 8, 2019 Category: Drugs & Pharmacology Authors: Sakurai Y Tags: Yakugaku Zasshi Source Type: research

Knockdown of sphingomyelin synthase 2 inhibits osteoclastogenesis by decreasing RANKL expression in mouse primary osteoblasts.
Abstract Sphingomyelin is a major lipid of the plasma membrane and is enriched in microdomains of the plasma membrane that are critical for signal transduction. However, the function of sphingomyelin in the cell membrane of osteoblasts has not been clarified. Therefore, we examined how sphingomyelin synthase 2 (SMS2) affects osteoclast differentiation by osteoblasts. We knocked down the expression of SMS2 with siRNA targeting the Sgms2 gene in mouse primary osteoblasts. The effects of SMS2 knockdown in osteoblasts were examined using polymerase chain reaction and western blotting. The knockdown of SMS2 suppressed ...
Source: Biomed Res - October 12, 2019 Category: Research Authors: Yoshikawa Y, Yoshizawa T, Domae E, Hirai Y, Kamada A, Okazaki T, Ikeo T Tags: Biomed Res Source Type: research

GDP-Bound Rab27a Dissociates from the Endocytic Machinery in a Phosphorylation-Dependent Manner after Insulin Secretion.
Abstract Glucose-stimulated insulin secretion is controlled by both exocytosis and endocytosis in pancreatic β-cells. Although endocytosis is a fundamental step to maintain cellular responses to the secretagogue, the molecular mechanism of endocytosis remains poorly defined. We have previously shown that in response to high concentrations of glucose, guanosine 5'-diphosphate (GDP)-bound Rab27a is recruited to the plasma membrane where IQ motif-containing guanosine 5'-triphosphatase (GTPase)-activating protein 1 (IQGAP1) is expressed, and that complex formation promotes endocytosis of secretory membranes after ins...
Source: Biological and Pharmaceutical Bulletin - September 3, 2019 Category: Drugs & Pharmacology Authors: Kimura T, Yamaoka M, Terabayashi T, Kaibuchi K, Ishikawa T, Ishizaki T Tags: Biol Pharm Bull Source Type: research

Reciprocal Regulation of Chaperone-Mediated Autophagy/Microautophagy and Exosome Release.
Abstract Autophagy-lysosome proteolysis is involved in protein quality control and classified into macroautophagy (MA), microautophagy (mA) and chaperone-mediated autophagy (CMA), by the routes of substrate delivery to lysosomes. Both autophagy-lysosome proteolysis and exosome release are strongly associated with membrane trafficking. In the present study, we investigated how chemical and small interfering RNA (siRNA)-mediated activation and inhibition of these autophagic pathways affect exosome release in AD293 cells. Activation of MA and mA by rapamycin and activation of CMA by mycophenolic acid significantly de...
Source: Biological and Pharmaceutical Bulletin - August 3, 2019 Category: Drugs & Pharmacology Authors: Oshima M, Seki T, Kurauchi Y, Hisatsune A, Katsuki H Tags: Biol Pharm Bull Source Type: research

Anti-RelA siRNA-Encapsulated Flexible Liposome with Tight Junction-Opening Peptide as a Non-invasive Topical Therapeutic for Atopic Dermatitis.
Abstract Small interfering RNA (siRNA) has been proposed as a novel treatment for atopic dermatitis (AD) because it suppresses sequence-specific mRNA expression. Indeed siRNA-based therapy achieves an almost complete cure with fewer side effects than currently available treatments. However, the tight junctions in the granular layer of the epidermis in the atopic skin are barriers to siRNA delivery. We previously reported the potential clinical utility of AT1002, a peptide that opens tight junctions. In the present study, we evaluated a topical siRNA-based therapy for AD using AT1002 in combination with a flexible ...
Source: Biological and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Ibaraki H, Kanazawa T, Kurano T, Oogi C, Takashima Y, Seta Y Tags: Biol Pharm Bull Source Type: research

BubR1 Is Essential for Thio-Dimethylarsinic Acid-Induced Spindle Assembly Checkpoint and Mitotic Cell Death for Preventing the Accumulation of Abnormal Cells.
In this study, we showed that thio-DMA promotes the phosphorylation of BubR1 protein, which is one of the constituents of the spindle assembly checkpoint (SAC) complex and accumulates in the cell in mitotic phase. Binding of Mad2 to CDC20, also known as the marker of the mitotic checkpoint complex (MCC) formation during the activation of SAC, was enhanced and mitotic associated cell death by apoptosis was promoted in HeLa cells but not in HepG2 cells. Basal BubR1 protein level in HepG2 was 10-times lower than that of HeLa cells. Consequently, BubR1 knockdown HeLa cells were generated by small interfering RNA (siRNA) techni...
Source: Biological and Pharmaceutical Bulletin - July 3, 2019 Category: Drugs & Pharmacology Authors: Kita K, Imai Y, Asaka N, Suzuki T, Ochi T Tags: Biol Pharm Bull Source Type: research

Impacts of CD40- and CD86-Silenced Antigen-Specific B Cells on the Control of Allergies.
CONCLUSION: This study showed, for the first time, that siRNA-induced CD86-silenced B cells significantly inhibited allergic responses and symptoms antigen-specifically, and that siRNA-induced CD40-/CD86-silenced antigen-specific B cells are a more useful antigen-specific therapy than CD40- or CD86-silenced B cells alone for the control of allergies. Furthermore, it was shown that CD40-/CD86-silenced B cells have stronger inhibition of IgE production and allergic symptoms than CD40-/CD86-silenced DCs. PMID: 31064207 [PubMed - as supplied by publisher]
Source: American Journal of Rhinology and Allergy - May 7, 2019 Category: ENT & OMF Authors: Suzuki M, Matsumoto T, Toyoda K, Nakamura Y, Murakami S Tags: Am J Rhinol Allergy Source Type: research

Naringenin Produces Neuroprotection Against LPS-Induced Dopamine Neurotoxicity via the Inhibition of Microglial NLRP3 Inflammasome Activation
Conclusions: This study demonstrated that NAR targeted microglial NLRP3 inflammasome to protect DA neurons against LPS-induced neurotoxicity. These findings suggest NAR might hold a promising therapeutic potential for PD. Background Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease. It is characterized by slow and progressive loss of dopamine (DA) neurons in the midbrain substantia nigra (SN) with the accumulation of α-synuclein in Lewy bodies and neuritis (1). Although the etiology of PD remains unclear, amounts of studies have suggested that ne...
Source: Frontiers in Immunology - April 30, 2019 Category: Allergy & Immunology Source Type: research