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Triple-negative breast cancer (TNBC) poses a significant global health challenge due to its highly aggressive nature and invasive characteristics. Dysregulation of the Hippo pathway, a key regulator of various biological processes, is observed in TNBC, and its inhibition holds promise for impeding cancer growth. This in-silico analysis investigates the role of Transcriptional Enhanced Associate Domain 4 (TEAD4) in TNBC and its interaction with Yes Associated Protein (YAP) in cancer progression. Our results demonstrate that TEAD4 upregulation is linked to poor prognosis in TNBC, emphasizing its critical role in the disease. Moreover, we identify CID44521006, an analog of Flufenamic acid, as a potential therapeutic compound capable of disrupting the TEAD4-YAP interaction by binding to the YAP-binding domain of TEAD4. These findings underscore the significance of TEAD4 in TNBC and propose CID44521006 as a promising candidate for therapeutic intervention. The study contributes valuable insights to advance treatment options for TNBC, offering a potential avenue for the development of targeted therapies against this aggressive form of breast cancer. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is second most common form of gynaecological cancer world wide. In this study, we collected and analyzed three ovarian cancer microarray raw datasets from Gene Expression Omnibus, NCBI, and identified a total of 1806 significant DEGs (Differentially expressed genes). The functional analysis of the DEGs showed that the 885 upregulated DEGs were mostly enriched in protein-binding activity, while the downregulated 796 genes were mostly enriched in retinal dehydrogenase activity and GABA receptor binding. We then constructed a protein–protein interaction network of the DEGs DEGs in ovarian cancer datasetsand analyzed the network to find cluster subnets, using molecular complex detection (MCODE). Common genes among top hub gene list, bottleneck gene list and maximum clique centrality (MCC) gene lists were identified as key driver genes, After analyzing the network. The following genes, STK12 (Serine threonine protein kinase), UBE2C (Ubiquitin-conjugating enzyme E2 C), CENPA (Centromere protein A), CCNB1 (Cyclin B1), POLD1 (polymerase delta 1) and KIF11 (Kinesin Family Member 11) were finally identified as driver genes. Higher expression of the key driver genes, STK12, UBE2C, CENPA, CCNB1, POLD1 and KIF11, was associated with lower overall survival (OS) among ovarian cancer patients. Therefore, the identified driver genes could be important diagnostic and prognostic biomarkers for predicting ovarian cancer progression and understanding the mechanism of tumour formation and recurrence. [ABSTRACT FROM AUTHOR]

The plant, Curcuma angustifolia Roxb., belonging to the family Zingiberaceae was subjected to a pot experiment to study the effects of arbuscular mycorrhizal fungi (AMF) on its metabolome. The experiment consisted of two treatments: Mycorrhizal (M), C. angustifolia plants inoculated with a consortium of AMF and non-mycorrhizal control plants (NM), plants not inoculated with AMF. GC-MS analyses revealed that AMF colonization modulated the composition and concentration of metabolites in different plant parts, leaves, rhizomes and roots as compared to their respective NM counterparts. However, n-hexadecanoic acid, 5-Hydroxymethylfurfural, 9, 12-octadecadienoic acid and terpineol were observed in all the parts in higher percentages. Cis-vaccenic acid was found in the highest concentration in rhizomes while roots showed a high concentration of coronarin E. These metabolites were found to possess good characteristics of being therapeutic drugs and their predicted targets are involved in different diseases such as obesity, diabetes mellitus, hypertension, cancers, etc. They also have many structurally similar compounds to the metabolites which are active against various protein targets involved in different diseases. Among them, terpineol has the Androgen receptor (AR) as the highest probable target whose roles have been reported in several cancers, especially prostate cancer. AR showed a thermodynamically favourable binding affinity with terpineol (ΔG = -6.2 kcal/mol). Similarly, other metabolites also showed binding affinities with their predicted targets. Thus, in the study, we report various metabolites of C. angustifolia and their potential characteristic drug-like properties, which may serve as a green alternative for better health care to mankind. [ABSTRACT FROM AUTHOR]

Dicranella pseudosubulata Müll Hal. ex Gangulee is a moss species and a member of the Dicranaceae family, which is known to harbour many secondary metabolites of therapeutic importance. A gas chromatography-mass spectrometry (GC-MS) analysis of the methanolic extract of D. pseudosubulata was obtained to determine the metabolites of the moss. The chromatogram revealed 48 compounds, of which four compounds showed the highest concentrations, constituting 73.86% of all the bioactive chemicals detected. The compound d-Glucitol, 1-O-heptyl-showed the highest area percentage of 45.70 per cent. Other compounds with high concentrations are 9,12-Octadecadienoic acid (Z, Z)-, TMS derivative (13.35%); Palmitic acid, TMS derivative (9.46%) and Butanoic acid, 4-[(trimethylsilyl)oxy]-, trimethylsilyl ester (5.35%). These metabolites were then examined for their drug-like characteristics using SwissADME and predicted for potential target proteins using SwissTargetPrediction tools. Molecular docking analyses with the most probable targets of d-Glucitol, 1-O-heptyl-;9,12-octadecadienoic acid; Palmitic acid, TMS derivative and Butanoic acid, 4-[(trimethylsilyl)oxy]-, trimethylsilyl ester with Beta-glucocerebrosidase (GBA), Peroxisome proliferator-activated receptor gamma (PPARG), fatty acid binding protein (FABP4) and Thymidylate synthase (TYMS), respectively, showed thermodynamically favourable bindings. The target proteins have been reported to be associated with various ailments and their inhibition by these compounds is necessary to control and maintain cell growth in several cancers as well as in treating malaria and leishmania, obesity, lipidosis, kidney necrosis, liver carcinoma, insulin resistance etc. Some of the compounds have been reported to exhibit antimicrobial, antioxidant, and hepatoprotective activities. Thus, the finding suggests that D. pseudosubulata could serve as a potential therapeutic drug against various diseases. [ABSTRACT FROM AUTHOR]

Abstract: Globally only 5–10% of people encountering Mycobacterium tuberculosis have a lifetime risk of active disease indicating a strong host genetic bias towards development of tuberculosis. In the current study we investigated genotype variants pertaining to five cytokine genes namely IFNG, TNFA, IL4, IL10 and IL12 in the north Indian population with active pulmonary tuberculosis (APTB) and correlated the serum cytokine levels with the corresponding genotypes. Twenty five single nucleotide polymorphisms (SNPs) including six loci examined for the first time in tuberculosis were selected for genotyping in 108 patients with APTB from north India and 48 healthy regional controls (HC). Applying exclusion criteria 12 SNPs passed all the filters and were analysed further. The serum cytokine concentrations were measured by ELISA. Compared to HC mean serum IFN-γ, IL-12, IL-4, and IL-10 levels were higher in APTB (p =0.3661, p =0.0186, p =0.003, p =0.7, respectively). In contrast the mean serum TNF-α level was higher in HC (p =0.007). Comparison of genotypes and serum levels of the corresponding cytokine genes reveal that though IFN-γ and IL-4 levels were higher in APTB the genotype variants showed no difference between HC and APTB. In contrast the genotypes of the selected rsIDs in the TNFA, IL12 and IL10 genes showed significant association with the varying serum levels of corresponding cytokines. The variant of the TNFA gene at rs3093662, the IL12 gene at rs3213094 and rs3212220 and the IL10 gene at rs3024498 did show a strong indication to be of relevance to the immunity to tuberculosis. To our knowledge this is the first report from this region relating genotypes and serum cytokine levels in north Indian population. [Copyright &y& Elsevier]

Cordycepin (3′ deoxyadenosine) has been widely researched as a potential cancer therapy, but many diverse mechanisms of action have been proposed. Here, we confirm that cordycepin triphosphate is likely to be the active metabolite of cordycepin and that it consistently represses growth factor‐induced gene expression. Bioinformatic analysis, quantitative PCR and western blotting confirmed that cordycepin blocks the PI3K/AKT/mTOR and/or MEK/ERK pathways in six cell lines and that AMPK activation is not required. The effects of cordycepin on translation through mTOR pathway repression were detectable within 30 min, indicating a rapid process. These data therefore indicate that cordycepin has a universal mechanism of action, acting as cordycepin triphosphate on an as yet unknown target molecule involved in growth factor signalling. [ABSTRACT FROM AUTHOR]