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Rios George posted an update 6 months ago
Recent studies have found that microRNA-29a (miR-29a) levels are significantly lower in fibrotic livers, as shown with human liver cirrhosis. Such downregulation influences the activation of hepatic stellate cells (HSC). Phosphoinositide 3-kinase p85 alpha (PI3KP85α) is implicated in the regulation of proteostasis mitochondrial integrity and unfolded protein response (UPR) and apoptosis in hepatocytes. This study aimed to investigate the potential therapeutic role of miR-29a in a murine bile duct ligation (BDL)-cholestatic injury and liver fibrosis model. Mice were assigned to four groups sham, BDL, BDL + scramble miRs, and BDL + miR-29a-mimic. Liver fibrosis and inflammation were assessed by histological staining and mRNA/protein expression of representative markers. Exogenous therapeutics of miR-29a in BDL-stressed mice significantly attenuated glutamic oxaloacetic transaminase (GOT)/glutamic-pyruvic transaminase (GPT) and liver fibrosis, and caused a significant downregulation in markers related to inflammation (IL-1β), fibrogenesis (TGF-β1, α-SMA, and COL1α1), autophagy (p62 and LC3B II), mitochondrial unfolded protein response (UPRmt; C/EBP homologous protein (CHOP), heat shock protein 60 (HSP60), and Lon protease-1 (LONP1, a mitochondrial protease), and PI3KP85α within the liver tissue. An in vitro luciferase reporter assay further confirmed that miR-29a mimic directly targets mRNA 3′ untranslated region (UTR) of PI3KP85α to suppress its expression in HepG2 cell line. Our data provide new insights that therapeutic miR-29a improves cholestasis-induced hepatic inflammation and fibrosis and proteotstasis via blocking PI3KP85α, highlighting the potential of miR-29a targeted therapy for liver injury.Renal cancer would greatly benefit from new therapeutic strategies since, in advanced stages, it is refractory to classical chemotherapeutic approaches. In this context, lysosomal protease cysteine cathepsins may represent new pharmacological targets. In renal cancer, they are characterized by a higher expression, and they were shown to play a role in its aggressiveness and spreading. Traditional studies in the field were focused on understanding the therapeutic potentialities of cysteine cathepsin inhibition, while the direct impact of such therapeutics on the expression of these enzymes was often overlooked. In this work, we engineered two fluoromethyl ketone-based peptides with inhibitory activity against cathepsins to evaluate their potential anticancer activity and impact on the lysosomal compartment in human renal cancer. Molecular modeling and biochemical assays confirmed the inhibitory properties of the peptides against cysteine cathepsin B and L. Different cell biology experiments demonstrated that the peptides could affect renal cancer cell migration and organization in colonies and spheroids, while increasing their adhesion to biological substrates. Finally, these peptide inhibitors modulated the expression of LAMP1, enhanced the expression of E-cadherin, and altered cathepsin expression. In conclusion, the inhibition of cysteine cathepsins by the peptides was beneficial in terms of cancer aggressiveness; however, they could affect the overall expression of these proteases.Poly(methyl-methacrylate) (PMMA) is a biocompatible and non-biodegradable polymer widely used as biomedical material. PMMA microcapsules with suitable dimension and porosity range are proposed to encapsulate live cells useful for tissue regeneration purposes. The aim of this work was to evaluate the feasibility of producing cell-loaded PMMA microcapsules through “high efficiency vibrational technology” (HEVT). this website Preliminary studies were conducted to set up the process parameters for PMMA microcapsules production and human dermal fibroblast, used as cell model, were encapsulated in shell/core microcapsules. Microcapsules morphometric analysis through optical microscope and scanning electron microscopy highlighted that uniform microcapsules of 1.2 mm with circular surface pores were obtained by HEVT. Best process conditions used were as follows frequency of 200 Hz, voltage of 750 V, flow rate of core solution of 10 mL/min, and flow rate of shell solution of 0.5 bar. Microcapsule membrane allowed permeation of molecules with low and medium molecular weight up to 5900 Da and prevented diffusion of high molecular weight molecules (11,000 Da). The yield of the process was about 50% and cell encapsulation efficiency was 27% on total amount. The cell survived and growth up to 72 h incubation in simulated physiologic medium was observed.Sensor networks are essential for the development of the Internet of Things and the smart city. A general sensor, especially a mobile sensor, has to be driven by a power unit. When considering the high mobility, wide distribution and wireless operation of the sensors, their sustainable operation remains a critical challenge owing to the limited lifetime of an energy storage unit. In 2006, Wang proposed the concept of self-powered sensors/system, which harvests ambient energy to continuously drive a sensor without the use of an external power source. Based on the piezoelectric nanogenerator (PENG) and triboelectric nanogenerator (TENG), extensive studies have focused on self-powered sensors. TENG and PENG, as effective mechanical-to-electricity energy conversion technologies, have been used not only as power sources but also as active sensing devices in many application fields, including physical sensors, wearable devices, biomedical and health care, human-machine interface, chemical and environmental monitoring, smart traffic, smart cities, robotics, and fiber and fabric sensors. In this review, we systematically summarize the progress made by TENG and PENG in those application fields. A perspective will be given about the future of self-powered sensors.Background Chikungunya fever is caused by the chikungunya virus. Numerous factors affect the risk of chikungunya transmission. This study explored the epidemiological characteristics, differences, and trends in domestic and imported cases of chikungunya fever in Taiwan in terms of patient sex, age, month of confirmation, and area of residence from 2007 to 2019. Methods Public annual chikungunya data from Taiwan’s Centers for Disease Control (CDC) were analyzed. In total, 21 confirmed domestic and 198 imported cases of chikungunya were reported. Of the domestic cases, one was sporadic and reported in July 2019, and 20 were attributed to a cluster event during August and September 2019. Results In a comparison between domestic and imported cases reported from July to October 2019, differences in sex were nonsignificant (p = 0.555), whereas significant differences were observed for age (p less then 0.001), month of confirmation (p = 0.005), and place of residence (p = 0.001). An age of 69-69 years (odds ratio (OR) = 6.