[This corrects the article on p. 6671 in vol. 7, PMID: 25400746.].
[This corrects the article on p. 6671 in vol. 7, PMID: 25400746.].
Background: Age-related macular degeneration (AMD) is a complex disease with a pathophysiology that remains incompletely understood. PCSK7 is closely related to the normal development of ocular tissues; however, the roles and mechanisms of PCSK7 in AMD have yet to be elucidated. Therefore, the purpose of this study was to investigate the specific manifestations of PCSK7 in AMD.
Methods: An AMD cell model was established by using hydrogen peroxide (H2O2)-treated ARPE-19 cells. The efficiency of PCSK7 overexpression was analyzed by western blotting (WB) and quantitative reverse transcription PCR (RT-qPCR). Subsequently, a Cell Counting Kit 8 (CCK-8) assay was employed to assess the proliferation of ARPE-19 cells, while flow cytometry and immunofluorescence were utilized to examine apoptosis. Iron accumulation and glutathione (GSH) levels in cells were measured using Enzyme-linked immunosorbent assay (ELISA), and WB was conducted to evaluate the expression of anti-ferroptosis protein. Finally, JC-1 staining was performed to assess mitochondrial membrane potential.
Results: Overexpressing of PCSK7 enhanced the proliferation and inhibited the apoptosis of ARPE-19 cells treated with H2O2. Additionally, increased PCSK7 expression suppressed intracellular iron levels and GSH content, thereby inhibiting the ferroptosis process. Furthermore, overexpression of PCSK7 restored mitochondrial membrane potential, alleviating H2O2-induced mitochondrial damage.
Conclusions: PCSK7 might be one of the targets for the treatment of AMD through the regulation of retinal epithelial cell death.
Background: Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators that promote the transcription of genes in the chromatin region associated with acetylated histones. Small molecule BET inhibitor JQ1 suppresses the biologic function of BET proteins in a variety of tumors and inhibits their proliferation.
Methods: We investigated the effect of JQ1 in the treatment of pancreatic cancer. In addition, we evaluated the expression level of BRD4 protein in pancreatic cancer tissues using the Gene Expression Profiling Interactive Analysis (GEPIA) and the Human protein Altas databases and analyzed the correlation between BRD4 and the clinicopathologic features and immune checkpoints of pancreatic adenocarcinoma using UALACN and TIMER databases.
Results: JQ1 significantly inhibited the proliferation of pancreatic adenocarcinoma (PAAD) cells and induced cell senescence but had little effect on Senescence-associated secretory phenotype (SASP). Interestingly, JQ1 inhibited the epithelial-mesenchymal transition (EMT) and Wnt signaling pathways.
Conclusions: These results provide a theoretical basis for new targets in the treatment of pancreatic cancer.
Objective: The aim of the present study was to investigate the expression of erythroblast transformation specific-1 related gene (ERG) in patients with glioblastoma (GB) before and after bevacizumab (Bev) therapy as a predictive and prognostic biomarker.
Methods: The present study used 58 GB tissues from 29 patients in 3 settings. Sixteen tumors were removed after neoadjuvant Bev administration (neoBev) and 13 represented newly diagnosed GB without previous Bev treatment (naïve Bev). Another 29 specimens of recurrence were obtained from salvage surgery or autopsy.
Results: Immunohistochemical analysis showed both vessel density (VD) and ERG score were decreased in neoBev compared with naïve Bev. VD and ERG score tended to be lower at recurrence than at initial surgery (P=0.0026 and P=0.1338, respectively). In the naïve Bev and neoBev cohorts, overall survival (OS) with high and low expressions of ERG was comparable (P=0.7516 and P=0.3862, respectively).
Conclusion: High expression of ERG in GB with naïveBev was significantly reduced with Bev, but not changed in refractoriness. Stratification of ERG expression levels might provide a useful predictive biomarker for GB treated with Bev.
Objective: Copper, an essential metal element for humans, plays vital functions in cancer prognosis and immunity. SLC31A1, a high-affinity copper transporter, helps regulate copper homeostasis and has been implicated in tumor prognosis through mechanisms such as drug resistance, autophagy, ferroptosis, and cuproptosis. However, the role of SLC31A1 in breast cancer (BRCA) and its association with tumor immune infiltration has not been fully elucidated. This study aimed to investigate the expression pattern of SLC31A1, its clinical significance, and its effect on tumor immune infiltration in BRCA.
Methods: We comprehensively analyzed multiple datasets, including Gene Expression Profiling Interaction Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), UALCAN, and Kaplan-Meier (KM) plotter, to assess the expression of SLC31A1 and its prognostic value in BRCA. Additionally, TIMER and TISIDB were used to explore the correlation between SLC31A1 expression and the extent of tumor immune infiltration.
Results: SLC31A1 was significantly upregulated in BRCA tissues compared to adjacent non-tumor tissues. Higher SLC31A1 expression levels were associated with poorer clinical outcome. Multivariate Cox regression analysis confirmed that SLC31A1 served as an independent prognostic indicator. Furthermore, SLC31A1 expression showed significant associations with various immunomodulators, chemokines, chemokine receptors, and tumor-infiltrating lymphocytes (TILs), including CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), follicular helper T cells (Tfh), neutrophils, M2 macrophages, tumor-associated macrophages (TAMs), and monocytes. These findings suggest that SLC31A1 may regulate macrophage polarization and T cell exhaustion in BRCA, contributing to immune evasion and poor prognosis.
Conclusion: Our study underscores the importance of further research to explore the therapeutic potential of targeting SLC31A1 and to uncover its additional roles in BRCA beyond the known mechanisms of drug resistance, autophagy, ferroptosis, and cuproptosis.
The use of medicinal plants in the management or prevention of diseases is one of the oldest human medicinal practices worldwide. Justicia carnea and Jatropha carcus are widely reported for their use in the management of blood disorders, hypertension, and diabetes.
Objective: The study aimed at evaluating the effects of hydroethanolic leaf extracts of Justicia carnea and Jatropha carcus on the biochemical, hematological, and histological parameters of apparently healthy rats.
Methodology: Thirty adult rats (n = 30) with an average weight of 153 g were randomly divided into six groups (A-F). Group A: negative control; Group B: positive control; Group C: Jatropha curcas (low dose); Group D: Jatropha curcas (high dose); Group E: Justicia carnea (low dose); and Group F: Justicia carnea (high dose). Standard and scientifically approved methods were used for sacrifice and laboratory diagnosis.
Results: The study shows a significant increase in body weight across groups administered with the leaf extracts. Elevated levels of serum creatinine were recorded in rats administered with both extracts, indicating nephrotoxicity. The study also observed an increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase across groups, indicating hepatotoxicity. Both extracts caused an increase in white blood cell count and hemoglobin concentration, a significant reduction in bleeding time, increased prothrombin time, and partial thromboplastin time at high dosages. Total iron binding capacity and serum ferritin values were increased in high doses and were statistically significant at P<0.05. Histomorphology of both extracts shows hepatorenal toxicity at high concentrations and none in the lungs or heart. Oral administration of Justicia carnea and Jatropha carcus extracts at high concentrations is not safe for the liver and kidneys.
Conclusion: Biochemical parameters should be monitored regularly in humans exposed to both plants. Therefore, this study scientifically confirms and supports the traditional use of the leaves of Jatropha carcus and Justicia carnea to enhance hematological parameters.
Background: Increasing air pollution has drawn our attention to particulate matter (PM2.5), which has been shown to correlate significantly with respiratory and cardiovascular systems. However, whether PM2.5 is causally associated with Alzheimer's syndrome or delirium is unclear.
Methods: We retrieved the genetic summary data of PM2.5 from genome-wide association studies (GWAS). The genetic information for Alzheimer's disease was obtained from the IEU OpenGWAS project, and that for delirium was obtained from FinnGen. We used two-sample Mendelian randomization analysis (MR) to associate PM2.5 with Alzheimer's disease or delirium.
Results: The odds ratio (OR) for Alzheimer's disease was 0.996 with a p-value of 0.443 using the inverse variance weighted algorithm, and the OR associated with the outcome variable of delirium was 0.393 with a p-value of 0.343.
Conclusion: With the exclusion of confounding factors, our findings do not support a genetic association between PM2.5 and Alzheimer's disease or delirium. Further population-based and experimental studies are needed to dissect the complex correlation between PM2.5 and Alzheimer's disease or delirium.
[This retracts the article on p. 2989 in vol. 12, PMID: 31934136.].
Lung cancer is the most prevalent and lethal disease globally, with approximately 80% of cases being non-small cell lung cancer (NSCLC). NSCLC is primarily composed of lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Despite chemotherapy currently being the primary treatment for NSCLC, chemotherapy resistance remains a significant challenge for patients. Recent studies have proposed immunotherapy as a promising new avenue for treating NSCLC. The association between the lysyl oxidase-like 2 (LOXL2) gene and NSCLC was explored using multiple online tools and bioinformatics analysis software based on the available datasets from TCGA. The immune microenvironment of the tumor was explored by calculating ImmuneScore, StromalScore, and TumorPurity of LUAD and LUSC and analyzing the infiltration of 22 immune cells in lung cancer tissues. LOXL2-related loads were obtained from the Xena database for LUSC and LUAD patients, and relevant prognostic genes were identified by analyzing survival curves. Functional and pathway enrichment analyses of prognostic, predictive genes were performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of LOXL2 in NSCLC was detected by RT-qPCR. LOXL2 may be involved in the progression of LUAD and LUSC and is closely related to the T-lymphocyte subpopulation, T-reg cells. SEMA7A and VEGFC are identified as the genes that interact with LOXL2 and could be used as prognostic signature genes in NSCLC patients. LOXL2 may become a prognostic marker and a new target for immunotherapy.
This study investigates the influence of CYP3A4 gene polymorphisms on postoperative pain sensitivity and analgesic response in lung cancer patients undergoing intercostal nerve block with local anesthetics. Sixty patients (ages 31-74) undergoing thoracoscopic lung cancer surgery were enrolled and divided into two groups based on CYP3A4 gene expression level: Group I (high CYP3A4) and Group II (low CYP3A4). Postoperative pain was assessed using the Visual Analogue Scale (VAS), and patient-controlled intravenous analgesia (PCIA) pump usage, ECG ST-T segment changes, complications, hospital stay, and costs were recorded. Results showed significantly higher VAS scores, PCIA usage, ST-T depression, complications, longer hospital stay, and higher costs in Group I compared to Group II (P < 0.05). These findings suggest that higher CYP3A4 expression is associated with increased postoperative pain, complications, and healthcare cost. According to CYP3A4 gene expression activity, which was determined before surgery, patients with low enzyme activity metabolized local anesthetics slowly, which resulted in better analgesic effect and a longer duration of intercostal nerve block anesthesia. Owing to the impact of CYP3A4 gene expression on local anesthetic metabolism, precise intercostal nerve block anesthesia and individualized pain treatment plans could be formulated for patients undergoing radical thoracoscopic surgery for lung cancer. This may accelerate postoperative recovery from lung cancer and reduce both the length of hospital stay and hospitalization costs.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：