Small interfering RNA for cancer treatment: overcoming hurdles in delivery

© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies

Dynamics of Prolyl hydroxylases levels during disease progression in experimental colitis

Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD

Hepatic Mitochondrial Damage Aggravated By Azathioprine: Protective Effect of Quercetin

Mitochondrian play an important role in the production of energy and cell cycle regulation. Administration of azathioprine (AZA), an immunosuppressant drug, adversely affects the hepatic mitochondria which may culminate  hepatotoxicity. The present study was undertaken to evaluate the effect of quercetin (QE), against AZA induced hepatic injury in Wistar rats. AZA (50 mg/kg body weight, i.p.) was administered once on the 7th day of experiment. A significant depletion in the levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase  (GPx) and reduced glutathione (GSH) were observed in AZA alone treated rats. Simultaneous decrease in the levels of tricarboxylic acid (TCA) enzymes such as isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (α-KGDH ), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were observed. Decrease in the levels of these enzymes suggests a loss in mitochondrial function and integrity. Lipids existing in the mitochondrial membrane were peroxidised, and measured by the production of   malondialdehyde (MDA). The supplementation of QE (50mg/kg body weight) restored the depleted levels of enzymes and above hepatic mitochondrial abnormality to near normalcy. The present study highlights the antioxidant property of QE in improving the mitochondrial functions in AZA induced hepatic degradatio

Hepatic Mitochondrial Damage Aggravated By Azathioprine: Protective Effect of Quercetin

Mitochondrian play an important role in the production of energy and cell cycle regulation. Administration of azathioprine (AZA), an immunosuppressant drug, adversely affects the hepatic mitochondria which may culminate  hepatotoxicity. The present study was undertaken to evaluate the effect of quercetin (QE), against AZA induced hepatic injury in Wistar rats. AZA (50 mg/kg body weight, i.p.) was administered once on the 7th day of experiment. A significant depletion in the levels of manganese superoxide dismutase (MnSOD), glutathione peroxidase  (GPx) and reduced glutathione (GSH) were observed in AZA alone treated rats. Simultaneous decrease in the levels of tricarboxylic acid (TCA) enzymes such as isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (α-KGDH ), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were observed. Decrease in the levels of these enzymes suggests a loss in mitochondrial function and integrity. Lipids existing in the mitochondrial membrane were peroxidised, and measured by the production of   malondialdehyde (MDA). The supplementation of QE (50mg/kg body weight) restored the depleted levels of enzymes and above hepatic mitochondrial abnormality to near normalcy. The present study highlights the antioxidant property of QE in improving the mitochondrial functions in AZA induced hepatic degradatio