Current Medicinal Chemistry - Online First

This study aimed to construct a diagnostic risk model for Bipolar Disorder (BD) using inflammation-related genes (IRGs) and to explore the role of immune cell infiltration in BD pathogenesis.

BD datasets (GSE23848, GSE124326, GSE39653, and GSE46449) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the edgeR package. The intersection of DEGs and IRGs was defined as differentially expressed IRGs. A LASSO regression model was used to identify optimal biomarkers, which were then utilized to construct a diagnostic risk model. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic accuracy of the biomarkers. Internal validation was performed with GSE124326, while external validation utilized GSE23848, GSE39653, and GSE46449. The xCell module in the IOBR package was employed to assess immune cell infiltration proportions. The relationship between IRGs, the diagnostic risk model, and immune cell dynamics was further analyzed.

A total of 2345 DEGs were identified in GSE124326. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that inflammatory pathways are critically involved in BD pathogenesis. A total of 69 BD-related IRGs were identified. Six key IRGs (IL33, DNASE1L3, IL2RA, CD70, CLEC5A, and SLPI) were identified through LASSO regression analysis and used to develop a diagnostic risk model. Internal and external validations confirmed the robust diagnostic performance of the risk model. Immuno-infiltration analysis showed significant differences in immune cell infiltration between BD patients and healthy controls. The diagnostic risk model and four potential biomarkers (DNASE1L3, IL2RA, CD70, and SLPI) showed strong correlations with various immune cell types.

A diagnostic risk model for BD was constructed based on IRGs, highlighting the critical role of immune cell infiltration in BD pathogenesis.

The precise function of DDX59 Antisense RNA 1 (DDX59-AS1) in lung adenocarcinoma (LUAD) has yet to be fully elucidated.

This study uses bioinformatics analysis and experimental validation to investigate the association between DDX59-AS1 and LUAD.

This study uses statistical analysis and database interrogation to investigate the potential association between DDX59-AS1 expression and various clinical characteristics, prognostic factors, regulatory networks, and immune infiltration in LUAD. The quantification of DDX59-AS1 expression in LUAD cell lines is conducted through the use of quantitative real-time polymerase chain reaction (qRT-PCR).

DDX59-AS1 showed significantly elevated levels of expression in patients with LUAD. High levels of DDX59-AS1 expression were found to be significantly associated with poorer overall survival (OS) in patients with LUAD (p = 0.024). Furthermore, an independent correlation was observed between high DDX59-AS1 expression (p = 0.037) and OS in LUAD patients. DDX59-AS1 was found to be involved in various pathways, including glutathione metabolism, proteasome function, and the cytosolic DNA sensing pathway, among others. A significant correlation was observed between the expression levels of DDX59-AS1 and immune cell infiltration in the context of LUAD. Notably, elevated expression of DDX59-AS1 was observed in LUAD cell lines compared to the non-cancerous Beas-2B cell line.

A significant correlation was observed between elevated DDX59-AS1 expression in patients with LUAD and adverse prognosis, alongside increased immune infiltration. These results indicate that DDX59-AS1 may function as a prognostic marker for LUAD and a potential predictor of immunotherapy response.

A series of benzylidene derivatives of fenobam and its thio analogues (1-22) have been evaluated for their cytotoxicity against breast cancer (MCF-7, MDA-MB-231), ovarian cancer (A2780, SKOV-3) and cervical cancer (HELA) cell lines.

These compounds (1-22) exhibited 72-83% inhibition of Erk activity against the ovarian cancer cell line (A2780). Compounds 3 and 20 showed the highest DNA damage effect in Comet Assay against the A2780 cancer cell line as compared to the other tested analogues (4, 8, 11, 12, and 13) by using % Tail DNA and OTM. Compounds 3, 4, and 11 showed significant activities and selectivity towards COX-2 with 78%, 97%, and 89% inhibition, as compared to 17%, 57%, and 26% inhibition against COX-1 isoenzyme, respectively.

Interestingly, molecular docking scores were also in very good agreement with the experimental results regarding discriminating the selectivity index of the tested compounds against COX-1 & COX-2 enzymes. Further molecular dynamics (MD) simulation study revealed that the most selective compound, 13, binds with the COX-2 enzyme in a similar fashion to that of Rofecoxib, which was further supported by their MD-based free binding energies (MM-GBSA) of -49.76 ± 4.27 kcal/mol, and -44.84 ±3.78 kcal/mol, respectively.

Moreover, in silico ADMET predictions showed adequate properties for these compounds, making them promising leads worthy of further optimization.

Prosopis juliflora has been employed in many traditional treatments. As evidenced by our earlier research, Prosopis juliflora leaf methanol extract (PJME) has a promising future in the fight against lung cancer. It may also be used in conjunction with other treatments to effectively manage lung cancer. Aims and objective: The main objective of this study was to explore the potential of PJME to inhibit lung cancer in A549 cells, along with its underlying mechanisms of action.

The antiproliferative effects were determined using MTT and LDH tests. Apoptosis-inducing capacity was evaluated using the DAPI staining, caspase-3 test, cytochrome C assay, PARP cleavage, and qRT-PCR. To investigate the mechanism of action of PJME in lung cancer, the levels of ROS, MMP, GSH, MDA, and specific ferroptosis indicators were measured.

The experimental data of the current study indicated that exposure of A549 cells to PJME reduced cell viability and increased cellular cytotoxicity. The apoptosis-inducing ability of PJME in A549 cells was validated by enhanced nuclear condensation, level of the caspase-3, cytochrome C, and PARP release. In addition, qRT-PCR investigations verified that the administration of PJME led to a decrease in the expression of anti-apoptotic gene Bcl2 while enhancing the mRNA level of pro-apoptotic genes, such as Bax and caspase-3, in A549 cells.

The study also found that PJME has the ability to activate ferroptosis pathways, as evidenced by elevated reactive oxygen species (ROS) generation, changes in the levels of antioxidant markers (MDA and GSH), and decreased expression of SLC7A11 and GPX4. The results of the present study clearly showed that PJME inhibited the proliferation of A549 cells and induced ferroptosis by reducing the expression of the important targets SLC7A11 and GPX4. Further research is necessary to fully understand the clinical efficacy of PJME before it can be investigated as supplemental or adjuvant therapy for lung cancer.

Menopause symptoms may be distressing, especially when they appear at a time when women are expected to play significant responsibilities in society. Numerous biological systems are influenced by the hormonal changes that start during the menopausal transition. This review attempts to decipher the complex relationship between obesity, menopause, and depression, citing some recent longitudinal and cross-sectional studies. Additionally, this study provides a summary of the different phytoestrogens, their sources, and probable mechanisms of action in addition to available therapeutic alternatives.

For this review purpose, the authors have gone through a vast number of articles from various scientific databases like PubMed, Google Scholar, and Web of Science.

It is becoming clear that the physiological basis for these menopausal symptoms is complicated and connected to estrogen deficiency, but not alone. Other hormones like FSH, LH, progesterone, and inhibin B are the major ones that are both directly and indirectly responsible for most of the menopausal symptoms. Numerous longitudinal and cross-sectional studies have found a direct relationship between the incidence of menopause and depression as well as obesity. Phytoestrogens like stilbene, lignans, isoflavone, and coumestan have been reported to be the alternatives to synthetic estrogen with lesser side effects, as reported in various studies.

The complex relationship between depression, menopause, and obesity presents a complex obstacle to women's health and overall well-being. There might be a lot of promising prospects for revolutionary advancements in women's health during the menopausal stage in the future. Promising drug development that targets not just one but also the three conditions -obesity, menopause, and depression - as well as more thorough research are needed to improve the healthcare system for women who suffer from these conditions.