Hepatocellular carcinoma frequently exhibits evasion of apoptosis, rendering the anti-apoptotic Bcl-2 protein a pertinent therapeutic target. Steroids from Talaromyces stipitatus were evaluated as Bcl-2 inhibitors using molecular docking, molecular dynamics simulation, MMGBSA free-energy estimation, ADMET prediction, and DFT descriptors. Docking prioritized CPD2 over Paclitaxel. It also indicated accommodation within a conserved pocket supported by hydrogen-bond and hydrophobic interactions. Molecular dynamics suggested sustained stability and compactness for the CPD2-Bcl-2 complex. In contrast, the reference complex exhibited comparatively larger conformational excursions. MMGBSA favored CPD2, with improved net association attributable primarily to a reduced solvation penalty. ADMET profiling indicated limited aqueous solubility and a shared hERG II liability, while predicting no hepatotoxicity alert for CPD2. DFT descriptors were consistent with higher electronic responsiveness for CPD2 relative to the reference. These findings suggest that CPD2 may serve as a promising scaffold for developing Bcl-2-targeted therapeutic strategies against HCC. Future in vitro and in vivo studies are required to validate these computational predictions and guide lead optimization.
Pancreatic cancer remains one of the most lethal malignancies worldwide due to late diagnosis and limited therapeutic response. Gemcitabine is widely used as a first-line chemotherapeutic agent, and SH3D21 has been identified as a gemcitabine sensitizer in pancreatic cancer cells. Here, we investigated whether rs34416442 polymorphism of SH3D21 is associated with overall survival in a cohort of Iranian patients with pancreatic cancer. Peripheral blood samples were collected from 26 patients, and genotyping was performed. Patients were followed and survival outcomes were analyzed using Kaplan-Meier curves and the log-rank test. Three genotypes-TTT/TTT, TTT/T, and T/T-were identified with frequencies of 38%, 54%, and 8%, respectively. Significant differences in survival were observed among genotypes (p = 0.004). Patients carrying the T/T genotype exhibited markedly shorter mean overall survival (135 days) compared with those harboring at least one TTT allele (395 and 450 days). A recessive model further confirmed the reduced survival associated with the homozygous T/T genotype (p = 0.001). Stratified analyses showed that this association persisted in both gemcitabine-received (p = 0.006) and not-received (p = 0.016) subgroups. While different genotype-based survival patterns were observed among patients of the two groups. The TTT/T genotype showed the best survival in patients receiving gemcitabine, while TTT/TTT genotype did so in patients not receiving gemcitabine. These findings suggest SH3D21 rs34416442 as a potential predictive biomarker for pancreatic cancer.
Sirtuin 1 (SIRT1), an NAD⁺-dependent deacetylase, is involved in glucose homeostasis, insulin signaling, and inflammatory regulation, making it a potential molecular target in type 2 diabetes mellitus (T2DM). This case-control study investigated the association between serum SIRT1 levels, the SIRT1 promoter polymorphism rs7895833, and metabolic parameters in 150 patients with T2DM and 150 age- and sex-matched healthy controls. Serum SIRT1 concentrations were measured by ELISA, and rs7895833 genotyping was performed using allele-specific PCR. Clinical and biochemical variables were also assessed. Serum SIRT1 levels were significantly lower in patients with T2DM than in controls (p < 0.001) and showed significant inverse correlations with fasting plasma glucose (p = 0.001) and HbA1c (p < 0.001). Genotypic analysis revealed a significant difference in the distribution of the rs7895833 AG genotype between the two groups (p = 0.03), and under the overdominant model (AG vs. AA + GG), the heterozygous AG genotype was significantly associated with T2DM risk (OR = 1.81, p = 0.011), whereas no significant association was found between SIRT1 genotypes and circulating SIRT1 levels. These findings suggest that reduced SIRT1 is associated with hyperglycemia and poor glycemic control in T2DM. Overall, SIRT1 may serve as a potential biomarker and molecular mediator in T2DM pathogenesis. This study provides original data from a Middle Eastern population and may help inform future mechanistic and comparative studies.
The tribe Arabideae includes various species worldwide with ornamental features; however, it has undergone taxonomic revisions and has been reclassified into different genera. Despite the available literature, the taxonomic assignment of some taxa requires further consideration. This study therefore addresses the true taxonomic position of Arabis verna (L.) W.T.Aiton, which is not phylogenetically nested within other Arabis species but is instead closely related to Aubrieta Adans,. The species is naturally distributed in Southwest Asia, North Africa, and South Europe, and its taxonomic delimitation has remained unresolved. Phylogenetic evidence from previous authorities, together with our morphological observations, supports the distinct status of A. verna from the genus Aubrieta. Consequently, A. verna is excluded from Aubrieta and transferred to a newly established genus, Pseudoarabis A.R. Khosravi & A. Eslami-Farouji gen. nov., and the new combination, P. verna (L.) A.R. Khosravi & A. Eslami-Farouji comb. nov. is proposed.
Psoriasis patients were 4- 5 times more likely to have S. aureus colonize their skin. Psoriasis is caused by staphylococcal infection-induced keratinocyte death, which is maintained by elevated cytokine production of TNF-α and IFN-γ. The study sought to determine the association between the influence of gene expression of certain genes in psoriasis infections in the presence of S. aureus and their effect in Skin Cutaneous Melanoma infections. GEO with accession number (GSE207390) was used to acquire the data. The microarray test was used to perform this investigation. Six sets of keratinocytes, IL-17A, and TNF-α were cultivated together. Several kinds of bioinformatics tools were employed to fulfill the study's objective. Gene hub analysis of 34284 genes was scanned. Six genes demonstrated high expression rates were expressed during the metastatic stage: CCL27, IL19, PAPPA2, UHRF1, IFNAR2, and GLS2. IFNAR2 and UHRF1 had the highest levels of expression. The expression of the COL4A4 gene rose in response to sun exposure, but the expression of the other genes remained same. The existence of cytokine groups with S. aureus in keratinocytes influences the expression difference compared to the other groups. This work adds to our understanding of the molecular alterations that occur in the epidermis of psoriasis patients, as well as their relationship to comorbidities.
