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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]

Introduction: Artemisia absinthium (wormwood) exhibits anticancer properties by inhibiting proliferation and causing cell death in breast cancer. Targeted drug delivery of A. absinthium nanoformulation using N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid-based polymeric nanoparticles (NVA-AA NPs) was ensured by utilizing features of the tumor microenvironment, although their mechanism of action involved in cytotoxicity remains unknown. Methods: The present study employed nano LC-MS/MS to identify differences in secretory protein expression associated with the treatment of breast cancer cell lines (MCF-7; MDA-MB-231) by NVA-AA NPs for the determination of affected pathways and easily accessible therapeutic targets. Different bioinformatics tools were used to identify signature differentially expressed proteins (DEPs) using survival analysis by GENT2 and correlation analysis between their mRNA expressions and sensitivity toward small-molecule drugs as well as immune cell infiltration by GSCA. Results: Analysis by GENT2 revealed 22 signature DEPs with the most significant change in their expression regulation, namely, gelsolin, alpha-fetoprotein, complement component C3, C7, histone H2B type 1-K, histone H2A.Z, H2AX, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1-like, cytochrome c somatic, GTP-binding nuclear protein Ran, tubulin beta chain, tubulin alpha-1B chain, tubulin alpha-1C chain, phosphoglycerate mutase 1, kininogen 1, carboxypeptidase N catalytic chain, fibulin-1, peroxiredoxins 4, lactate dehydrogenase C, SPARC, and SPARC-like protein 1. Correlation analysis between their mRNA expressions versus immune cell infiltrates showed a positive correlation with antitumor immune response elicited by these NPs as well as a correlation with drug response shown by the GDSC and CTRP drugs in different cancer cells. Discussion: Our results suggest that NVA-AA NPs were able to invade the tumor microenvironment; transformed the communication network between the cancer cells; affected potential drivers of microtubular integrity, nucleosome assembly, and cell cycle; and eventually caused cell death. [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]

Network medicine provides network theoretical tools, methods and properties to study underlying laws governing human interactome to identify disease states and disease complexity leading to drug discovery. Within this framework, we investigated the topological properties of ovarian cancer network (OCN) and the roles of hubs to understand OCN organization to address disease states and complexity. The OCN constructed from the experimentally verified genes exhibits fractal nature in the topological properties with deeply rooted functional communities indicating self-organizing behavior. The network properties at all levels of organization obey one parameter scaling law which lacks centrality lethality rule. We showed that |$\langle k\rangle $| can be taken as a scaling parameter, where, power law exponent can be estimated from the ratio of network diameters. The betweenness centrality |$C_B$| shows two distinct behaviors one shown by high degree hubs and the other by segregated low degree nodes. The |$C_B$| power law exponent is found to connect the exponents of distributions of high and low degree nodes. OCN showed the absence of rich-club formation which leads to the missing of a number of attractors in the network causing formation of weakly tied diverse functional modules to keep optimal network efficiency. In OCN, provincial and connector hubs, which includes identified key regulators, take major responsibility to keep the OCN integrity and organization. Further, most of the key regulators are found to be over expressed and positively correlated with immune infiltrates. Finally, few potential drugs are identified related to the key regulators. [ABSTRACT FROM AUTHOR]

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]

Background: Breast cancer is the leading cause of frequent malignancy and morbidity among women across the globe, with an increment of 0.5% incidences every year. The deleterious effects of traditional treatment on off-target surrounding cells make it difficult to win the battle against breast cancer. Hence, an advancement in the therapeutic approach is crucial. Nanotechnology is one of the emerging methods for precise, targeted, and efficient drug delivery in cells. The previous study has demonstrated the cytotoxic effect of Ipomoea turpethum extract on breast cancer cells delivered via NIPAAM-VP-AA nanoparticles (NVA-IT). Manipulating the tumor microenvironment (TME) to inhibit cancer progression, invasion, and metastasis seems to be very insightful for researchers these days. With the help of secretome analysis of breast cancer cells after treatment with NVA-IT, we have tried to find out the possible TME manipulation achieved to favor a better prognosis of the disease. Method: MCF-7 and MDA MB-231 cells were treated with the IC 50 value of NVA-IT, and the medium was separated from the cells after 24 h of the treatment. Nano LCMS/MS analysis was performed to identify the secretory proteins in the media. Further bioinformatics tools like GENT2, GSCA, GeneCodis 4, and STRING were used to identify the key proteins and their interactions. Result: From the nano LCMS/MS analysis, 70 differentially expressed secretory proteins in MCF-7 and 191 in MDA MB-231 were identified in the cell's media. Fifteen key target proteins were filtered using bioinformatics analysis, and the interaction of proteins involved in vesicular trafficking, cell cycle checkpoints, and oxidative stress-related proteins was prominent. Conclusion: This study concluded that I. turpethum extract-loaded NIPAAM-VP-AA nanoparticles alter the secretory proteins constituting the TME to cease cancer cell growth and metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Swami, Mughees, Mangangcha, Kauser and Wajid.)