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Development of an Alcohol Dilution-Lyophilization Method for Preparing Lipid Nanoparticles Containing Encapsulated siRNA.
In this study, we report on the development of an "alcohol dilution-lyophilization method" for preparing siRNA-encapsulating LNPs. This method involves the use of a freeze-drying (lyophilization) method to remove the residual alcohol and to simultaneously concentrate the preparation. At first, the compositions of cryoprotectants and polyethylene glycol (PEG)-lipids that were used were optimized from the point of view of particle stabilization. A combination of sucrose and 1-(monomethoxy polyethyleneglycol5000)-2,3-dimyristoylglycerol (DMG-PEG5000) was found to have the most efficient cryoprotective activity for the LNPs. T...
Source: Biological and Pharmaceutical Bulletin - August 3, 2018 Category: Drugs & Pharmacology Authors: Shirane D, Tanaka H, Nakai Y, Yoshioka H, Akita H Tags: Biol Pharm Bull Source Type: research

Suppressing autophagy enhances disulfiram/copper-induced apoptosis in non-small cell lung cancer.
Abstract Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells. The present study is designed to investigat...
Source: European Journal of Pharmacology - March 13, 2018 Category: Drugs & Pharmacology Authors: Wu X, Xue X, Wang L, Wang W, Han J, Sun X, Zhang H, Liu Y, Che X, Yang J, Wu C Tags: Eur J Pharmacol Source Type: research

Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy.
Abstract Hepatic fibrosis is a reversible wound-healing response to either acute or chronic liver injury caused by hepatitis B or C, alcohol, and toxic agents. Hepatic fibrosis is characterized by excessive accumulation and reduced degradation of extracellular matrix (ECM). Excessive accumulation of ECM alters the hepatic architecture leading to liver fibrosis and cirrhosis. Cirrhosis results in failure of common functions of the liver. Hepatic stellate cells (HSC) play a major role in the development of liver fibrosis as HSC are the main source of the excessive production of ECM in an injured liver. RNA interfere...
Source: Pharmacological Reviews - August 17, 2016 Category: Drugs & Pharmacology Authors: Omar R, Yang J, Liu H, Davies NM, Gong Y Tags: Rev Physiol Biochem Pharmacol Source Type: research

RNA Interference as a Therapeutic Strategy for the Treatment of Liver Diseases.
Abstract RNA interference has emerged as an innovative technology for gene silencing that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs (siRNAs). Its therapeutic application has important advantages over small-molecule drugs since offers the possibility of targeting virtually all genes and allows selective silencing of one or several genes. So far, a relative small proportion of cellular proteins can bind and respond to chemical drugs. Based on that, RNA interference-mediated gene silencing is widely considered as a crucial breakthrough in molecular biology with a...
Source: Current Pharmaceutical Design - October 23, 2015 Category: Drugs & Pharmacology Authors: Gonzalez-Rodriguez A, Valverde AM Tags: Curr Pharm Des Source Type: research

Salsalate and Adiponectin Ameliorate Hepatic Steatosis by Inhibition of the Hepatokine Feutin-A.
In conclusion, salsalate and fAd improved palmitate-induced steatosis and impairment of lipid metabolism in hepatocytes via fetuin-A inhibition through the AMPK-NFκB pathway. PMID: 23948064 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - August 12, 2013 Category: Drugs & Pharmacology Authors: Jung TW, Youn BS, Choi HY, Lee SY, Hong HC, Yang SJ, Yoo HJ, Kim BH, Baik SH, Choi KM Tags: Biochem Pharmacol Source Type: research

Quercetin and allopurinol reduce liver thioredoxin‐interacting protein to alleviate inflammation and lipid accumulation in diabetic rats
Conclusions and ImplicationsInhibition of hepatic TXNIP by quercetin and allopurinol contributes to the reduction in liver inflammation and lipid accumulation under hyperglycaemic conditions. The targeting of hepatic TXNIP by quercetin and allopurinol may have therapeutic implications for prevention of type 1 diabetes‐associated NAFLD.
Source: British Journal of Pharmacology - June 21, 2013 Category: Drugs & Pharmacology Authors: Wei Wang, Chuang Wang, Xiao‐Qin Ding, Ying Pan, Ting‐Ting Gu, Ming‐Xing Wang, Yang‐Liu Liu, Fu‐Meng Wang, Shui‐Juan Wang, Ling‐Dong Kong Tags: Research Paper Source Type: research

Sulforaphane protects against ethanol‐induced oxidative stress and apoptosis in neural crest cells by the induction of Nrf2‐mediated antioxidant response
Conclusions and implicationsThese results demonstrated that Nrf2‐mediated antioxidant response plays an important role in the susceptibility of NCCs to ethanol‐induced oxidative stress and apoptosis and that the protection of SFN against ethanol‐induced oxidative stress and apoptosis in NCCs is mediated by the induction of Nrf2 signaling.
Source: British Journal of Pharmacology - February 20, 2013 Category: Drugs & Pharmacology Authors: X Chen, J Liu, S‐Y Chen Tags: Research Paper Source Type: research

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