Nonalcoholic fatty liver disease (NAFLD) is now a leading cause of chronic liver disease, and there is currently no available treatment strategy. Interleukin-22 (IL-22) has been recognized as a promising agent for alleviating NAFLD, but the efficacy of IL-22 is far from satisfactory because safe dose of IL-22 elicited limited improvement, whereas higher concentration might induce serious side effects and off-target toxicities. Thus, targeted and sustained expression of IL-22 in the liver is necessary. To meet the challenge, we elaborately developed a novel polymetformin carrier by conjugating biguanide to chitosan, termed chitosan–metformin (CM), which could exert advanced gene delivery efficiency and possess intrinsic therapeutic efficacy from metformin for NAFLD. CM accompanied with penetratin and DSPE-PEG2000 could self-assemble to form stable nanocomplexes with IL-22 gene via electrostatic interaction. This nanoparticle (CDPIA) exerted desirable particle size at ∼100 nm, fine morphology, and efficient cellular internalization. Furthermore, CDPIA also demonstrated a unique superiority in endosomal escape capacity and satisfactory biocompatibility as well as predominant liver accumulation. Most importantly, CDPIA distinctly alleviated hepatic steatosis, restored insulin sensitivity, and improved metabolic syndrome in high-fat-diet-fed mice model. This liver-targeted delivery of IL-22 activated STAT3/Erk1/2 and Nrf2/SOD1 signaling transductions as well as modulated lipid-metabolism-related gene expression. These findings altogether demonstrated that the polymetformin and penetratin-based hybrid nanoparticles could be exploited as a novel safe and efficient strategy for the improvement of NAFLD.

BackgroundMethylation of tumor suppressor gene promoter leads to transcription inactivation and is involved in tumorigenesis. Several studies demonstrate a potential association between the Death-Associated Protein Kinase (DAPK) gene promoter methylation and bladder cancer risk, tumor stage and histological grade. Due to inconsistent results of these studies, we performed this meta-analysis to ascertain the association.MethodsStudies were retrieved from the PubMed, Embase, Web of Science and the Cochrane Library databases. Study selection and data extraction were executed by two reviewers independently. Meta-analysis was performed using Stata 13.0 and Review Manager 5.3 software.ResultsA total of 21 articles involving 15 case control and 8 case series studies were included in this meta-analysis. DAPK promoter methylation was associated with bladder cancer risk (OR: 5.81; 95%CI = 3.83–8.82, P<0.00001). The frequency of DAPK promoter methylation was equal in bladder cancer tissue and paired adjacent normal tissue (OR: 0.87; 95%CI = 0.31–2.48, P = 0.794). Furthermore, DAPK promoter methylation was associated with higher histological grade (OR: 1.52; 95%CI = 1.10–2.09, P = 0.011) but not associated with tumor stage (OR: 1.12; 95%CI = 0.67–1.87, P = 0.668).ConclusionsThe result suggests that DAPK promoter methylation is significantly increased in bladder cancer patients compared to normal controls. DAPK promoter methylation could serve as a biomarker for bladder cancer detection and management.

Intense pulsed light combined with lattice CO laser treatment can improve cleft lip surgery scar pliability and appearance, while alleviating children from having to endure the pain of scar massage.

Nephroblastoma, or Wilms tumor, is a primary renal malignant tumor that easily occurs in children. Previous studies have revealed the regulatory functions of LncRNA in nephroblastoma. LncRNA HAGLROS functions as a tumor promotor in various cancers including hepatocellular carcinoma, ovarian cancer and colorectal cancer. In this study, the HAGLROS expression in nephroblastoma cells was assayed through qRT-PCR. Cell proliferation assessment employed CCK-8. Moreover, the migration and invasion of cells were examined separately through wound healing and transwell assay. Moreover, flow cytometric analysis and Western blot assay were applied to evaluate cell apoptosis. Rapamycin and 3-methyladenine were used to serve as autophagy activator or inhibitor, respectively. In addition, autophagy was identified by immunofluorescence staining and Western blot analysis. Experiment results showed that HAGLROS expressed highly in nephroblastoma cell lines. HAGLROS knockdown prevented cells from proliferating, and also showed suppressive impact on migration and invasion in HFWT cells. In addition, knockdown of HAGLROS showed a facilitative effect on apoptosis and an inhibitory effect on autophagy. Stimulation of autophagy alleviated HAGLROS silencing-induced apoptosis, while inhibition of autophagy reversed the effect in nephroblastoma cells. In summary, our results revealed that HAGLROS executed an oncogenic role in the progress of nephroblastoma, offering a new perspective on the strategy for nephroblastoma therapy.