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Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture
Polychlorinated biphenyls (PCBs) are persistent and highly toxic pollutants, which can accumulate in organisms and produce toxic effects, especially damaging the function of thyroid hormones. So far, the molecular mechanism of PCBs mixture and their metabolites interfering with thyroid hormones has not been studied thoroughly except for individual compounds. In this study, PubMed, Web of Science, and STITCH databases were used to search PCBs and their corresponding target proteins. The intersection of PCBs and thyroid hormone dysfunction target proteins was obtained from GeneCards. The “compounds-targets-pathways” network was constructed by Cytoscape software. And KEGG and Go analyses were performed for key targets. Finally, molecular docking was used to verify the binding effect. Four major active components, five key targets, and 10 kernel pathways were successfully screened by constructing the network. Functional enrichment analysis showed that the interference was mediated by cancer, proteoglycans, PI3K-Akt, thyroid hormone, and FoxO signaling pathways. The molecular docking results showed that the binding energies were less than -5 kcal·mol-1. PCBs and their metabolites may act on the key targets of MAPK3, MAPK1, RXRA, PIK3R1, and TP53. The toxic effect of sulfated and methyl sulfone PCBs is greater. The method of screening targets based on the simultaneous action of multiple PCBs can provide a reference for other research. The targets were not found in previous metabolite toxicity studies. It also provides a bridge for the toxic effects and experimental research of PCBs and their metabolites in the future.
MicroRNA-34c-5p exhibits anticancer properties in gastric cancer by targeting MAP2K1 to inhibit cell proliferation, migration, and invasion
Purpose. Gastric cancer(GC)is one of the deadliest digestive tract tumors worldwide，existing studies suggest that dysregulated expression of microRNAs (miRNAs) plays an important role in the pathogenesis and progression of GC. This study aimed to investigate the expression, biological function, and downstream mechanism of miR-34c-5p in GC, provide new targets for gastric cancer diagnosis and treatment. Methods. The expression of miR-34c-5p in GC tissues and cell lines was examined by RT-qPCR. Cell wound healing, transwell and cell cloning assays were used to detect the effect of miR-34c-5p on the migration and invasion abilities, respectively, of GC cells. Western blot was performed to detect the expression of related proteins. Bioinformatics analysis was used to predict the binding of MAP2K1 to miR-34c-5p and the targeting relationship was confirmed by dual luciferase reporter assay. Results. The expression level of miR-34c-5p was significantly decreased in GC tissues and cell lines. miR-34c-5p overexpression inhibited migration, invasion, and colony formation of gastric cancer cells, the related protein E-cadherin expression was significantly increased and N-cadherin, vimentin, and PCNA expression were significantly decreased, while miR-34c-5p knockdown exerted the opposite effects. In addition, the targeting relationship between miR-34c-5p and MAP2K1 was predicted and confirmed, and further confirmed by rescue experiments that MAP2K1 alleviated the inhibitory effect of miR-34c-5p in GC. Conclusion. MiR-34c-5p is lowly expressed in GC, and it can target MAP2K1 to exert inhibitory effects on GC proliferation, invasion, and migration. These findings provide a promising biomarker and a potential therapeutic target for gastric cancer.
Mastication Wear of Two Low Profile Attachment Systems for Overdenture: An In Vitro Study
Background. Edentulism is still a major problem in the world’s population today. Implant-retained overdenture has proven to be a valid therapeutic solution in the mandible. This type of rehabilitation requires replacement of the matrices when those reach inadequate retention due to wearing processes. This study is aimed at evaluating the drop in retention of low-profile precision attachments following the application of vertical chewing forces. Two different attachment designs were compared. Methods. This in vitro study simulated an implant-retained overdenture on an edentulous mandible. Two low-profile attachments were compared. Loaded and unloaded sides were considered. Tests were performed by exerting a vertical cyclic force on the prosthesis at the level of the first molar of a hemiarch. Retention tests were performed before and after 400.000 chewing cycles, comparable to one year of use. Results. The presence of vertical load wear was identified and characterized. Retention never fell below the values indicated by the manufacturer. Furthermore, significant differences were identified between the two retention systems. Conclusions. Loss of occlusal load retention is a component that must be evaluated by the clinician during the design of implant-prosthetic rehabilitation, particularly in those cases where elevated occlusal forces or parafunctions are present.
Influence of P(VDF-TrFE) Membranes with Different Surface Potentials on the Activity and Angiogenic Function of Human Umbilical Vein Endothelial Cells
During bone tissue regeneration, neovascularization is critical, and the formation of a blood supply network is crucial for bone growth stimulation and remodeling. Previous studies suggest that bioelectric signals facilitate the process of angiogenesis. Owing to their biomimetic electroactivity, piezoelectric membranes have garnered substantial interest in the field of guided bone regeneration. Nevertheless, the knowledge of their influence due to varying surface potentials on the progression of angiogenesis remains ambiguous. Therefore, we proposed the preparation of an electroactive material, P(VDF-TrFE), and investigated its effects on the activity and angiogenic functions of human umbilical vein endothelial cells (HUVECs). The HUVECs were directly cultured on P(VDF-TrFE) membranes with different surface potentials. Subsequently, cell viability, proliferation, migration, tube formation, and expressions of related factors were assessed through appropriate assays. Our results revealed that the negative surface potential groups exerted differential effects on the modulation of angiogenesis in vitro. The P(VDF-TrFE) membranes with negative surface potential exhibited the greatest effect on cellular behaviors, including proliferation, migration, tube formation, and promotion of angiogenesis by releasing key factors such as VEGF-A and CD31. Overall, these results indicated that the surface potential of piezoelectric P(VDF-TrFE) membranes could exert differential effects on angiogenesis in vitro. We present a novel approach for designing bioactive materials for guided bone regeneration.
In Vitro Evaluation of Extracellular Enzyme Activity and Its Biocontrol Efficacy of Bacterial Isolates from Pepper Plants for the Management of Phytophthora capsici
Phytophthora capsici is one of the most devastating fungal pathogens, causing severe diseases that lead to economic loss in the pepper industry. As a result of the infections, the chemical approach is becoming more popular. Biological control, on the other hand, is better suited to controlling fungal pathogens. The biological control approach significantly reduces the problems associated with chemical applications while restoring natural environmental balance. As a result, the overall findings indicate that certain bacterial isolates play a beneficial role in lytic enzyme production and biocontrol activities against P. capsici. Bacterial isolates obtained from the pepper plants were screened for lytic enzyme and anti-oomycete activity against Phytophthora capsici in Ethiopia. Sixty bacterial isolates were isolated and tested against Phytophthora capsici. From these bacterial isolates, different inhibition zones and hydrolytic enzyme production were detected. Biochemical tests using an automated machine (MALDI-TOF, VITEK 2 compact and 16S rRNA) revealed that three of them, AAUSR23, AAULE41, and AAULE51, showed a high inhibition zone and high production of hydrolytic enzymes and were identified as Enterobacter cloacae (AAUSR23), Pseudomonas fluorescens (AAULE41), and undetermined (AAULE51). The effects of diffusable metabolite isolate AAULE51 has a 66.7% inhibition zone against Phytophthora capsici, followed by AAULE41 and AAUSR23, which have 59.7% and 14.1% inhibition zones, respectively. These bacterial isolates showed high production of hydrolytic enzymes like protease, cellulase, chitinase, and lipase (5-34 diameter of inhibition zone). As a result, the overall findings show that selected bacterial isolates play a beneficial role in lytic enzyme production and for their biocontrol activities against P. capsici.
Network Pharmacology and Molecular Docking Analyses Unveil the Mechanisms of Yiguanjian Decoction against Parkinson’s Disease from Inner/Outer Brain Perspective
Objective. This study aims to explore the pharmacodynamic mechanism of Yiguanjian (YGJ) decoction against Parkinson’s disease (PD) through integrating the central nervous (inner brain) and peripheral system (outer brain) relationship spectrum. Methods. The active components of YGJ were achieved from the TCMSP, TCMID, and TCM@Taiwan databases. The blood-brain barrier (BBB) permeability of the active components along with their corresponding targets was evaluated utilizing the existing website, namely, SwissADME and SwissTargetPrediction. The targets of PD were determined through database retrieval. The interaction network was constructed upon the STRING database, followed by the visualization using Cytoscape software. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on potential targets. Finally, the molecular docking approach was employed to assess the binding affinity between key components and key targets. Results. Overall, we identified 79 active components, 128 potential targets of YGJ, and 97 potential targets of YGJ-BBB potentially suitable for the treatment of PD. GO and KEGG analyses showed that the YGJ treatment of PD mainly relied on PI3K-Akt pathway while the YGJ-BBB was mostly involved in endocrine resistance. The molecular docking results displayed high affinity between multiple compounds and targets in accordance with previous observations. Conclusions. Our study unveiled the potential mechanisms of YGJ against PD from a systemic perspective: (1) for the YGJ, they have potential exerting effects on the peripheral system and inhibiting neuronal apoptosis through regulating the PI3K-Akt pathway; (2) for the YGJ-BBB, they can directly modulate endocrine resistance of the central nervous and holistically enhance body resistance to PD along with YGJ on PI3K-Akt pathway.