Association between urinary metals and prostate-specific antigen in aging population with depression: a cross-sectional study.

Objective: This study aims to investigate the impact of depression and urinary metals on Prostate-Specific Antigen (PSA). Methods: Analysis was conducted on 1901 samples collected from the National Health and Nutrition Examination Survey (NHANES) database between 2001 and 2010. Analytical methods included stepwise multiple linear regression (MLR) analysis of the overall population's urinary metals and PSA relationship, analysis of urinary metals and PSA relationship in older adults and BMI subgroups, analysis of urinary metals and PSA relationship in the depressed population, and restricted cubic spline (RCS) analysis. A significance level of p < 0.05 was considered statistically significant. Results: In the stepwise multiple linear regression, beryllium (Be) showed a dose-response association with PSA (third quartile: ß = 0.05, 95%CI (0.02, 0.09); fourth quartile: ß = 0.07, 95%CI (0.02, 0.12), p trend = 0.048). Subgroup analysis indicated that in individuals aged >60, Be at Q4 level [ß = 0.09, 95%CI (0.05, 0.21)] exhibited a dose-response correlation with PSA. In the population with 25 ≤ BMI < 30, Be might more significantly elevate PSA, with Q4 level having a pronounced impact on PSA levels [ß = 0.03, 95%CI (0.02, 1.27)]. In the depressed population, urinary cadmium (Cd) levels showed a significant positive dose-response relationship, with Q4 level of Cd having the maximum impact on PSA [ß = 0.3, 95%CI (0.09, 0.49)]. Conclusion: Individuals exposed to beryllium (Be), especially the older adults and overweight, should monitor their PSA levels. In depressed patients, cadmium (Cd) levels may further elevate PSA levels, necessitating increased monitoring of PSA levels among males.

Bio-informatics and in Vitro Experiments Reveal the Mechanism of Schisandrin A Against MDA-MB-231 cells.

Schisandrin A (SchA) has been reported to have good anti-cancer effects. However, its anti-cancer mechanism in breast cancer remains unknown. This study aimed to explore the mechanism of SchA in breast cancer treatment using bio-informatics analysis and in vitro experiments. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Cards, and PharmMapper databases were used to screen the candidate targets of SchA against MDA-MB-231 cells selected as the tested cell line through MTT analysis. The functions and pathways of the targets were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and further analyzed using DAVID 6.8.1 database. Network pharmacology analysis revealed 77 candidate targets, 31 signal pathways, and 208 GO entries (P < 0.05). The targets regulated serine-type endopeptidase and protein tyrosine kinase activities, thereby promoting the migration and inhibiting the apoptosis of MDA-MB-231 cells. Comprehensive analysis of the 'Protein-Protein Interaction' (PPI) and 'Component-Targets-Pathways' (C-T-P) networks constructed using Cytoscape 3.7.1 software revealed four core targets: EGFR, PIK3R1, MMP9 and Caspase 3. Their docking scores with SchA were subsequently investigated through molecular docking. The wound healing, Hoechst 33342/PI, and western blot assays confirmed that SchA significantly down-regulated EGFR, PIK3R1, and MMP9, but up-regulated cleaved-caspase 3, thus inhibiting the migration and promoting the apoptosis of MDA-MB-231 cells. Reckoning the findings of the study, SchA is a potential adjuvant treatment for breast cancer.

Geniposide protects pulmonary arterial smooth muscle cells from lipopolysaccharide-induced injury via α7nAchR-mediated TLR-4/MyD88 signaling.

Geniposide is a bioactive iridoid glucoside derived from Gardenia jasminoides that has proven anti-inflammatory effects against acute lung injury. The aim of this study was to determine whether geniposide could protect pulmonary arterial smooth muscle cells (PASMCs) from lipopolysaccharide (LPS)-induced injury and to explore the participation of α7 nicotinic acetylcholine receptor (α7nAChR), which was previously reported to suppress pro-inflammatory cytokine production in LPS-stimulated macrophages. In the present study, rat PASMCs were isolated and stimulated using LPS. The effect of geniposide on LPS-induced PASMC injury was then explored. Geniposide exerted anti-apoptotic and anti-inflammatory effects on LPS-treated PASMCs, as demonstrated by the downregulation of pro-apoptotic proteins and pro-inflammatory cytokines, respectively. Furthermore, the α7nAChR agonist PNU282987 accentuated the protective effect of geniposide against LPS-induced injury in PASMCs by inhibiting toll-like receptor-4/myeloid differentiation primary response 88 (TLR-4/MyD88) signaling and downregulating nuclear factor (NF)-κB expression. Conversely, methyllycaconitine, an inhibitor of α7nAChR, attenuated the effects of geniposide. These findings collectively suggested that in conjunction with geniposide, the activation of α7nAChR may contribute to further mitigating LPS-induced PASMC apoptosis and inflammation. In addition, the underlying mechanisms critically involve the NF-κB/MyD88 signaling axis. These results may provide novel insights into the treatment and management of lung diseases via geniposide administration.

Triflavones from Selaginella Doederllein Inhibited Hypoxia-induced, Pulmonary Vascular Remodeling Through PI3K/Akt.

CONTEXT: Pulmonary hypertension (PH) is a complication of numerous pulmonary conditions. Previous studies have confirmed that Selaginella doederleini has pharmacological effects against many cancers, and triflavones have been newly isolated as one of its active ingredients, with antioxidant and antitumor activities. The chronic hypoxia model is one of the models most used to study PH pathogenesis and treatment. OBJECTIVE: The present study was designed to investigate the protective effects of triflavones from selaginella doederlleini against PH and on the proliferation and apoptosis of ASMCs in a hypoxia-induced PH model in rats. METHODS: The research team performed an animal study. SETTING: The study took place at the Tongji Medical College at the Huazhong University of Science and Technology in Wuhan, Hubei, PR China. ANIMALS: The animals were 40 specific pathogen free (SPF), male SD rats weighing 200 ± 20 g each. INTERVENTION: The animals were divided into 4 groups, with 10 animals in each group: (1) the control group, (3) the hypoxia group (PH group), (3) the control + triflavones group (Tri group) and (4) the hypoxia + triflavones group (PH + Tri group). The rats in 2 hypoxia groups were exposed to 10% oxygen to induce PH, and the animals in the 2 control groups were exposed to room air, both for 3 consecutive weeks. Animals in the 2 triflavones groups were injected with 200 µL of triflavones-100 mg/mL dissolved in 0.9% normal saline-and the animals in the control and PH groups were injected with 200 µL of 0.9% normal saline. OUTCOME MEASURES: In vitro, the primary aorta smooth muscle cells (ASMCs) were isolated, and the proliferation and apoptosis of the ASMCs were assayed by CCK-8 kit and flow cytometry. The expression levels of the alpha-smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-ß1), and phosphoinositide 3-kinases (P13K)/ protein kinase B (Akt) in the ASMCs were also assayed by Western blot. RESULTS: Triflavones effectively decreased mPAP, the ratio of RV/ (LV + S), and the thickness of the arteries of the PH + Tri group. Furthermore, triflavones reversed the increased proliferation and inhibited apoptosis induced by chronic hypoxia for that group. Hypoxia increased TGF-ß1 protein expression and the activation of P13K/Akt, as shown in the PH group, and was abrogated by the triflavones. CONCLUSION: Triflavones are promising protective agents against PH due to their inhibitory effects on vascular remodeling through P13K/Akt signaling.

Rational design to improve activity of the Est3563 esterase from Acinetobacter sp. LMB-5.

Acinetobacter sp. strain LMB-5 can produce a kind of esterase degrading phthalate esters. However, low activity of Est3563 esterase limited its large-scale application. In this study, computer-aided simulation mutagenesis was used to improve the esterase activity with a tightened screening library and enlarged success rate. Two positive mutants, P218R and A242R, were obtained with 2.5 and 2.1 folds higher than the WT Est3563 esterase, with 11.96 ± 0.45 U·mg-1 and 9.90 ± 0.52 U·mg-1, respectively. With the help of bioinformatics analysis and three-dimensional printing technology, it was found that the mutations could increase the 240-280 residues swing distance and make them deviate from the catalytic pocket. The instability and deviation of these residues on the lid-like structure of the esterase could deteriorate the seal of the binding pocket and expose the active site. Thus, the catalytic efficiency of the mutants became higher. This result demonstrates that the instability and deviation of the lid-like structure could expand the binding pocket of the esterase and enhance the esterase activity.

Characterization of antimicrobial activity of three Lactobacillus plantarum strains isolated from Chinese traditional dairy food.

Many Lactobacillus plantarum strains can secrete some antimicrobial substances and be added to food as antimicrobial agents and preservatives. In this study, three L. plantarum strains (P1, S11, and M7) with strong antimicrobial activity against three pathogenic bacteria were isolated from Xinjiang traditional dairy products. Five common organic acids produced by fermentation of strains play a key role in inhibiting three pathogenic bacteria. At the same pH, the antimicrobial activity of the fermentation broth against Escherichia coli and Salmonella is stronger than that of the organic acid alone. Thus, three kinds of antimicrobial agents (P1-1, M7-1, and S11-1) mixed with five common organic acids were produced. Moreover, the antimicrobial activity against Salmonella ASI.1174 of the antimicrobial agents was about 30% higher than that of the fermentation broth. In addition, organic acid antimicrobial agents combined in different proportions can inhibit different pathogenic bacteria. According to this result, it is a potential approach to develop novel antimicrobial agents used in food preservation by mixing different organic acids.

Enhanced l-ornithine production by systematic manipulation of l-ornithine metabolism in engineered Corynebacterium glutamicum S9114.

l-Ornithine is a non-protein amino acid with extensive applications in medicine and the food industry. Currently, l-ornithine is produced by microbial fermentation; however, this process needs to be further improved in terms of l-ornithine productivity and cost reduction. In this study, overexpression of LysE was observed to increase l-ornithine production in engineered Corynebacterium glutamicum S9114. To overcome the drawbacks of using a plasmid to express LysE, Ptac, a strong promoter, was inserted in the upstream region of lysE on the chromosome. This strain was further engineered by attenuating the expression of ncgl2228 and proB, and enhancing the expression of gdh and argCJBD. Combination of those targets resulted in l-ornithine production at a titer of 25 g/L, which was 63.4% higher than that produced by the original strain (15.3 g/L). These results demonstrated the positive effects of overexpressing LysE on l-ornithine production and provided novel targets for developing l-ornithine-producing C. glutamicum strains.