Molecular Pathogenesis of Preeclampsia: MicroRNA Hypothesis

The discovery of micro RNA (miRNA) in 1993 by Ambros and colleagues has a huge influence in pathogenesis theory, diagnosis and treatment approach of some diseases. Some studies have conducted to seek the association alterations of miRNA expression to incidences and severity of preeclampsia (PE). We have reviewed some studies that conducted to seek the association of miRNA and PE and we discussed the role of various miRNAs in PE pathogenesis. In summary, we have shown that many researchers have given evident that the different placental and plasma miRNA expression is associated with PE. Some studies also identified the novel candidate of miRNAs (and their pathways) that may be of etiologic relevance in the pathogenesis of PE. Base on review, specific miRNA have a role to down regulate of anti apoptosis genes, regulate angiogenics growth factors such as angiogenin, vascular endothelial growth factor (VEGF) B (VEGF-β), cysteine-rich 61 (CYR61), Placental growth factor (PlGF) and VEGF-A that have a role in angiogenesis. miRNA also have a role in survival, migration, and capillary tube formation of HUVEC by targeted of c-kit. Some miRNAs target genes that participate in immunologic dysfunction, cell adhesion, cell cycle, and signaling. miRNA also have a roles in endothelial cell response to hypoxia, cell differentiation, and survival. A miRNA influence calcium signaling through negative regulations of the calmodulin-coding mRNAs, Mef2a and Gata4, mainly in smooth muscle cells that contribute to PE pathogenesis. These investigations provide novel targets for further investigation of the pathogenesis of PE and these differential miRNAs may be potential markers for the diagnosis and provide a potential therapeutic target for PE. Further investigations on posttranscriptional regulation in PE to evaluate biologic effects of identified miRNAs (including confirmations of miRNA and target gene interactions) are neede

Peningkatan Disolusi Rosuvastatin Calsium Dari Sediaan Tablet Dengan Teknik Liquisolid Dan Pembentukan Kompleks Inklusi

Rosuvastatin calcium is a salt form of rosuvastatin with antilipidemia activity. Rosuvastatin Calcium classified in class two of Biopharmaceutics Clasification System (BCS)  has low solubility in water (17.96 mg / L) and high permeability. Based on this, rosuvastatin calcium needs to be formulated appropriately in order to produce high bioavailability and maximum therapeutic effect. The bioavailability of BCS 2 drug is determined by the dissolution rate of the drug in gastrointestinal fluid so that a technique is needed in formulating the drug. This study aims to develop a formulation technique for rosuvastatin calcium tablets through liquisolid technique and formation of inclusion complexes with β-cyclodextrin in order to increase the rate of dissolution. Tablet formulation with liquisolid technique was made with a concentration of 10% rosuvastatin calcium in propylene glycol, with a ratio of US2® (carrier) and Aerosil 200 (coating) made with a ratio of 10: 1 and 20: 1. In addition to the formulation with liquisolid technique, formulations were also carried out with the complex inclusion technique of rosuvastatin calcium-β-cyclodextrin using kneading method and freeze drying method with a mol ratio of 1: 1 and 1: 2. The liquisolid system and inclusion complexes formed were characterized using FTIR and SEM. Characterization results indicated changes in the form of polymorphous rosuvastatin calcium. Tablet formulations were made by direct compression using a liquisolid system and an inclusion complex equivalent to 10 mg of rosuvastatin calcium. Based on the results of the ANOVA statistical test and further LSD tests showed that calcium rosuvastatin tablets made with liquisolid and inclusion complexes can increase the dissolution rate compared to pure rosuvastatin calcium tablets and inovator rosuvastatin calcium tablets. The highest dissolution rate was produced by liquisolid R20: 1 tablet at 60 minutes at 85.53 ± 1.02% in an enzyme-free simulated gastric fluid dissolution medium and 110.02 ± 1.71% in an enzyme-free simulated intestinal fluid dissolution medium

Learning from the Viral Journey: How to Enter Cells and How to Overcome Intracellular Barriers to Reach the Nucleus

Viruses deliver their genome into host cells where they subsequently replicate and multiply. A variety of relevant strategies have evolved by which viruses gain intracellular access and utilize cellular machinery for the synthesis of their genome. Therefore, the viral journey provides insight into the cell’s trafficking machinery and how it can be best exploited to improve nonviral gene delivery systems. This review summarizes viral internalization pathways and intracellular trafficking of viruses, with an emphasis on the endosomal escape processes of nonenveloped viruses. Intracellular events from viral entry through nuclear delivery of the viral complementary DNA are also discussed