Deciphering key genes involved in cisplatin resistance in kidney renal clear cell carcinoma through a combined in silico and in vitro approach.

The low survival rate of Kidney renal clear cell carcinoma (KIRC) patients is largely attributed to cisplatin resistance. Rather than focusing solely on individual proteins, exploring protein-protein interactions could offer greater insight into drug resistance. To this end, a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC chemotherapy. The genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information (NCBI) database using search terms as "Kidney renal clear cell carcinoma" and "Cisplatin resistance". The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape tool. Expression and promoter methylation profiling of the hub genes was done using UALCAN, GEPIA, OncoDB, and HPA databases. Mutational, survival, functional enrichment, immune cell infiltration, and drug prediction analyses of the hub genes were performed using the cBioPortal, GEPIA, GSEA, TIMER, and DrugBank databases. Lastly, expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines (786-O and A-498) and a normal renal tubular epithelial cell line (HK-2) using two high throughput techniques, including targeted bisulfite sequencing (bisulfite-seq) and RT-qPCR. A total of 124 genes were identified as being associated with cisplatin resistance in KIRC. Out of these genes, MCL1, IGF1R, CCND1, and PTEN were identified as hub genes and were found to have significant (p < 0.05) variations in their mRNA and protein expressions and effects on the overall survival (OS) of the KIRC patients. Moreover, an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub genes. In addition to this, hub genes were also linked with different cisplatin resistance-causing pathways. Thus, hub genes can be targeted with Alvocidib, Estradiol, Tretinoin, Capsaicin, Dronabinol, Metribolone, Calcitriol, Acetaminophen, Acitretin, Cyclosporine, Azacitidine, Genistein, and Resveratrol drugs. As the pathogenesis of KIRC is complex, targeting hub genes and associated pathways involved in cisplatin resistance could bring a milestone change in the drug discovery and management of drug resistance, which might uplift overall survival among KIRC patients.

The importance of monitoring endocrine-disrupting chemicals and essential elements in biological samples of fertilizer industry workers.

Exposure to endocrine-disrupting chemicals (EDCs) can lead to adverse health effects, including immune and endocrine system disruption, respiratory problems, metabolic issues, diabetes, obesity, cardiovascular problems, growth impairment, neurological and learning disabilities, and cancer. Fertilizers, which contain varying levels of heavy metals, are known to pose a significant risk to human health, especially for those residing or working near fertilizer industries. This study aimed to investigate the levels of toxic elements in biological samples of individuals working in a fertilizer industry's quality control and production units and those residing within 100-500 m of the industry. Biological samples, including scalp hair and whole blood, were collected from fertilizer workers, individuals living in the same residential area, and control age-matched persons from nonindustrial areas. The samples were oxidized by an acid mixture before analysis using atomic absorption spectrophotometry. The accuracy and validity of the methodology were verified through certified reference materials from scalp hair and whole blood. The results showed that the concentrations of toxic elements, such as cadmium and lead, were higher in biological samples of quality control and production employees. In contrast, lower essential element levels (iron and zinc) were detected in their samples. These levels were higher than those found in samples collected from residents living within 10-500 m of the fertilizer manufacturing facilities and unexposed areas. This study highlights the significance of adopting better practices to reduce exposure to harmful substances and protect the health of fertilizer industry workers and the environment. It also suggests that policymakers and industry leaders should take measures to minimize exposure to EDCs and heavy metals to promote worker safety and public health. These measures could include implementing strict regulations and better occupational health practices to reduce toxic exposure and promote a safer work environment.

Evading the Entrepreneurship: A Study to Discover Implementable Online Approaches to Avoid Greenhouse Consequences.

Greenhouse gases emissions due to climate change are a continuous threat to the global world, mainly relying on the pervasive consumption of numerous products, including synthetic and non-synthetic products. This research focused on the green purchase intentions of students in Pakistan towards different products, which are related to minimising the greenhouse effect and are available for sale on numerous e-commerce websites, ultimately proceeding to green entrepreneurship. The main objective of this study was to determine which methodology was better among product listing, social media advertising, and online virtual community to enhance customer online green purchase intention while considering online information about the greenhouse effect as a mediating variable. The AMOS 24 was used for this research. SEM was performed with the help of bootstrap methodology. The research was conducted on 280 students at different educational institutes in Pakistan, using a simple random sampling technique. A finding of this study suggested that all three methods positively impacted the green purchase intention of consumers and green entrepreneurship, but online virtual communities could be considered in a more effective way to enhance the green purchase intention of its targeted customers.