Assessment of lipid metabolism-disrupting effects of non-phthalate plasticizer diisobutyl adipate through in silico and in vitro approaches.

Diisobutyl adipate (DIBA), as a novel non-phthalate plasticizer, is widely used in various products. However, little effort has been made to investigate whether DIBA might have adverse effects on human health. In this study, we integrated an in silico and in vitro strategy to assess the impact of DIBA on cellular homeostasis. Since numerous plasticizers could activate peroxisome proliferator-activated receptor γ (PPARγ) pathway to interrupt metabolism systems, we first utilized molecular docking to analyze interaction between DIBA and PPARγ. Results indicated that DIBA had strong affinity with the ligand-binding domain of PPARγ (PPARγ-LBD) at Histidine 499. Afterwards, we used cellular models to investigate in vitro effects of DIBA. Results demonstrated that DIBA exposure increased intracellular lipid content in murine and human hepatocytes, and altered transcriptional expression of genes related to PPARγ signaling and lipid metabolism pathways. At last, target genes regulated by DIBA were predicted and enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Protein-protein interaction (PPI) network and transcriptional factors (TFs)-genes network were established accordingly. Target genes were enriched in Phospholipase D signaling pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and Epidermal growth factor receptor (EGFR) signaling pathway which were related to lipid metabolism. These findings suggested that DIBA exposure might disturb intracellular lipid metabolism homeostasis via targeting PPARγ. This study also demonstrated that this integrated in silico and in vitro methodology could be utilized as a high throughput, cost-saving and effective tool to assess the potential risk of various environmental chemicals on human health.

Comparison of super-mini-PCNL and flexible ureteroscopy for the management of upper urinary tract calculus (1-2 cm) in children.

OBJECTIVES: To retrospectively evaluate the efficacy and safety of super-mini percutaneous nephrolithotomy (SMP) and retrograde intrarenal surgery (RIRS) for children with upper urinary tract calculus (1-2 cm). PATIENTS AND METHODS: Children with upper urinary tract calculus (1-2 cm) who underwent the SMP or RIRS were enrolled in this study. Patients were divided into two groups: group SMP, 36 patients; and group RIRS, 25 patients. Patients were evaluated with KUB radiography or CT after 1 month. The collected data were analyzed. RESULTS: The mean stone size was 14.18 mm in group SMP, and 14.00 mm in group RIRS (p = 0.812). Group RIRS compared to group SMP showed longer operating time [76.3 vs 53.9 min (p = 0.002)], and postoperative hospital stay [4.2 vs 2.9 days (p = 0.011)]. The overall stone-free rate (SFR) was 94.4% for group SMP, and 60.0% for group RIRS in 1 month after operation (p = 0.001). The re-treatment rate was significantly higher in group RIRS compared to group SMP [20.0% vs 0.0% (p = 0.009)]. The complication rate was 5.6%, and 24.0% for groups SMP, and RIRS, respectively (p = 0.036). CONCLUSIONS: SMP was more effective than RIRS to obtain a better SFR, less re-treatment rate, and complication rate in children with upper urinary tract calculus (1-2 cm).

The structural characterization and UV-protective properties of an exopolysaccharide from a Paenibacillus isolate.

Introduction: Overexposure to ultraviolet (UV) light is known to cause damage to the skin, leading to sunburn and photo-aging. Chemical sunscreen products may give rise to health risks including phototoxicity, photosensitivity, and photosensitivity. Natural polysaccharides have attracted considerable interests due to diverse biological activities. Methods: A novel polysaccharide isolated was purified and structurally characterized using chemical methods followed by HPLC, GLC-MS, as well as 1D and 2D NMR spectroscopy. The photoprotective effect of the EPS on UVB-induced damage was assessed in vitro using cultured keratinocytes and in vivo using C57BL/6 mouse models. Results: The average molecular weight of the EPS was 5.48 × 106 Da, composed of glucose, mannose and galactose residues at a ratio of 2:2:1. The repeating units of the EPS were →3)-ß-D-Glcp (1→3) [ß-D-Galp (1→2)-α-D-Glcp (1→2)]-α-D-Manp (1→3)-α-D-Manp (1→. In cultured keratinocytes, the EPS reduced cytotoxicity and excessive ROS production induced by UVB irradiation. The EPS also exhibits an inhibitory effect on oxidative stress, inflammation, and collagen degradation found in the photodamage in mice. 1H NMR-based metabolomics analysis for skin suggested that the EPS partly reversed the shifts of metabolic profiles of the skin in UVB-exposed mice. Conclusion: The EPS exhibits skin photoprotective effects through regulating oxidative stress both in vivo and in vitro. Our findings highlight that the EPS is a potential candidate in sunscreen formulations for an efficient solution to UVB radiation.

Efficacy of docetaxel combined carboplatin for the treatment of patients with castration-resistant prostate cancer: A protocol of systematic review and meta-analysis.

BACKGROUND: A numerous published studies have reported that docetaxel combined carboplatin (DC) has been utilized for the treatment of patients with castration-resistant prostate cancer (CRPC). However, there are still contradictory results. Therefore, this systematic review and meta-analysis will explore the efficacy and safety of DC for the treatment of patients with CRPC. METHODS: We will systematically and comprehensively search MEDLINE, EMBASE, Cochrane Library, Web of Science, CINAHL, WANGFANG, CBM, and CNKI from the beginning up to the March 1, 2020, regardless language and publication time. We will consider randomized controlled trials that evaluated the efficacy and safety of DC for the treatment of patients with CRPC. The treatment effects of all dichotomous data will be estimated as risk ratio and 95% confidence intervals (CIs), and that of continuous outcomes will be calculated as standardized mean difference or mean difference and 95% CIs. Methodological quality will be appraised by Cochrane risk of bias tool, and quality of evidence will be identified by Grading of Recommendations Assessment Development and Evaluation. Statistical analysis will be undertaken by RevMan 5.3 software. RESULTS: This study will systematically explore the efficacy and safety of DC for the treatment of patients with CRPC. CONCLUSION: This study may provide helpful evidence to determine whether DC is an effective treatment for patients with CRPC or not. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040076.