Conectar
by Congli Jia, Fu Yang
ObjectiveThis study employs integrated network toxicology and molecular docking to investigate the molecular basis underlying 4-nonylphenol (4-NP)-mediated enhancement of breast cancer susceptibility.
MethodsWe integrated data from multiple databases, including ChEMBL, STITCH, Swiss Target Prediction, GeneCards, OMIM and TTD. Core compound-disease-associated target genes were identified through Protein-Protein Interaction (PPI) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were subsequently employed to elucidate the potential molecular functions and biological pathways associated with these key targets. Molecular docking using AutoDock Vina was conducted to investigate the binding interactions between the core genes and 4-NP. Furthermore, the miRDB database was utilized to identify potential microRNAs (miRNAs) that may exert regulatory control over the pivotal genes.
ResultsFive hub breast cancer target genes associated with 4-NP exposure were screened, containing TP53, HDAC1, ESR1, CTNNB1 and MYC. GO and KEGG analyses revealed that intersecting genes mainly influenced PI3K-Akt signaling, MicroRNAs in cancer, Chemical carcinogenesis−receptor activation and MAPK signaling. Molecular docking confirmed strong binding affinities of 4-NP to these hub genes. Subsequently several high-confidence candidate regulatory miRNAs especially miR-22, -148a, -181a and −152 were identified that shed light on miRNA regulatory mechanisms by which 4-NP increases breast cancer risk.
ConclusionOur study demonstrates that 4-NP exposure perturbs protein conformational of hub targets, activating cascades and dysregulating signaling pathway to potentiate breast cancer risk. Furthermore, we identify a novel miRNA-mediated regulatory axis alongside MAPK signaling as critical mechanisms underpinning 4-NP toxicity.
The utilization of 27-G TSV, or 27-Gauge Transconjunctival Sutureless Vitrectomy, poses distinct difficulties in the context of paediatric patients, particularly those younger than 14 years old, on account of the dearth of exhaustive documentation concerning the efficacy and results of these operations. Therefore, this retrospective study was to evaluate the safety and efficacy of 27-G TSV in paediatric patients, with emphasis on management of intraoperative and postoperative complications and postoperative wound healing. A total of 54 eyes of 52 paediatric patients who underwent 27-G TSV at Sichuan Provincial People's Hospital were included in the study. The average duration of follow-up was 9.32 ± 3.35 months. The complication with the highest incidence rate was Rhegmatogenous Retinal Detachment (RRD), which was detected in 27.8% cases. Familial Exudative Vitreoretinopathy (FEVR) and Persistent Fetal Vasculature (PFV) each accounted for 16.7% of the cases. Retinopathy of Prematurity (ROP) and Vitreous Haemorrhage (VH) constituted 11.1% and 14.8%, respectively, of the reported cases. Lens injury (1.9%), cannula slippage (7.4%) and wound leakage (5.6%) were intraoperative complications. Iatrogenic retinal detachment occurred at 3.7%. Hypotony (10.8% of patients), vitreous haemorrhage (9.3%), cataract formation (9.3%), ocular hypertension (8.1%) and retinal detachment (5.6%) were postoperative complications. Effective management strategies were executed, such as performing in situ trocar puncture to address cannula slippage and promptly suturing to address wound leakage. 27-G TSV exhibited promise as the therapeutic alternative for range of vitreoretinal disorders in paediatric patients, accompanied by complications that were controllable during and after the procedure. Strict preoperative planning and precise surgical technique are indispensable in order to maximize patient outcomes and guarantee effective wound healing and recovery within this particular demographic.
This systematic review and meta-analysis evaluate the impact of ultrasound-guided subsheath versus extrasheath sciatic nerve blocks on postoperative wound pain in tibial and foot surgeries, crucial for effective pain management and patient recovery. Adhering to PRISMA guidelines, this study used a PICO framework, focusing on patients undergoing tibial and foot surgeries and comparing the efficacy and safety of subsheath and extrasheath sciatic nerve blocks. The literature search spanned four databases without time restrictions, assessing various outcomes like success rate, onset time, duration of analgesia and complication rates. Quality assessment employed the Cochrane Collaboration's risk of bias tool, and statistical analyses included heterogeneity assessment, fixed-effect and random-effects models, sensitivity analysis and publication bias evaluation using funnel plots and Egger's linear regression test. From an initial pool of 1213 articles, six met the inclusion criteria. The subsheath group showed a significantly higher success rate of complete sensory blockade within 30 min compared with the extrasheath group (OR = 5.39; 95% CI: 2.82–10.28; p < 0.01). No significant differences were found in procedure duration or incidence of nerve-related complications between the two techniques. The subsheath approach also demonstrated a quicker onset time of sensory blockade (MD = −8.57; 95% CI: −11.27 to −5.88; p < 0.01). Sensitivity analysis confirmed the stability of the results, and no significant publication bias was detected. Ultrasound-guided subsheath sciatic nerve blocks are more effective than extrasheath blocks in achieving rapid and complete sensory blockade for tibial and foot surgeries, with a quicker onset time and comparable safety profile. Subsheath injections are thus recommended as a preferred method for anaesthesia and postoperative pain management in these surgical procedures, enhancing overall patient outcomes.
Diabetic foot ulcer, is a chronic complication afflicting individuals with diabetes, continue to increase worldwide, immensely burdening society. Programmed cell death, which includes apoptosis, autophagy, ferroptosis, necroptosis and pyroptosis, has been increasingly implicated in the pathogenesis of diabetic foot ulcer. This review is based on an exhaustive examination of the literature on ‘programmed cell death’ and ‘diabetic foot ulcers’ via PubMed. The findings revealed that natural bioactive compounds, noncoding RNAs and certain proteins play crucial roles in the healing of diabetic foot ulcers through various forms of programmed cell death, including apoptosis, autophagy, ferroptosis and pyroptosis.
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