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Breast cancer is a prevalent and potentially life-threatening disease that affects women worldwide. Natural products have gained attention as potential anticancer agents due to their fewer side effects, low toxicity, and cost effectiveness compared to traditional chemotherapy drugs. In the current study, the network pharmacology approach was used following a molecular docking study to evaluate the therapeutic potential of N. sativa -derived phytochemicals against breast cancer. Specifically, the study aimed to identify potential anticancer agents targeting key proteins implicated in breast cancer progression. Five proteins (i.e., EGFR, MAPK3, ESR1, MAPK1, and PTGS2) associated with breast cancer were selected as receptor proteins. Fourteen phytochemicals from N. sativa were prioritized based on drug-likeness (DL) and oral bioavailability (OB) parameters (with criteria set at DL > 0.18 and OB > 30%, respectively). Subsequent analysis of gene targets identified 283 overlapping genes primarily related to breast cancer pathogenesis. Ten hub genes were identified through topological analysis based on their significance in the KEGG pathway and GO annotations. Molecular docking revealed strong binding affinities between folic acid, betulinic acid, stigmasterol, and selected receptor proteins. These phytochemicals also demonstrated druggability potential. In vitro experiments in the MDA-MB-231 breast cancer cell line revealed that betulinic acid and stigmasterol significantly reduced cell viability after 24 h of treatment, confirming their anticancer activity. Furthermore, in vivo evaluation using a DMBA-induced rat model showed that betulinic acid and stigmasterol contributed to the significant recovery of cancer markers. This study aimed to explore the mechanisms underlying the anticancer potential of N. sativa phytochemicals against breast cancer, with the ultimate goal of identifying novel therapeutic candidates for future drug development. Overall, these results highlight betulinic acid and stigmasterol as promising candidates to develop novel anticancer agents against breast cancer. The comprehensive approach of this study, which integrates network pharmacology and molecular docking study and its experimental validation, strengthens the evidence supporting the therapeutic benefits of N. sativa -derived phytochemicals in breast cancer treatment, making them promising candidates for the development of novel anticancer agents against breast cancer., Competing Interests: The authors declare no conflicts of interest.

The bending resonance of micro-sized resonators has been utilized to study adsorption of analyte molecules in complex fluids of picogram quantity. Traditionally, the analysis to characterize the resonance frequency has focused solely on the mass change, whereas the effect of interfacial tension of the fluid has been largely neglected. By observing forced vibrations of a microfluidic cantilever filled with a series of alkanes using a laser Doppler vibrometer (LDV), we studied the effect of surface and interfacial tension on the resonance frequency. Here, we incorporated the Young-Laplace equation into the Euler-Bernoulli beam theory to consider extra stress that surface and interface tension exerts on the vibration of the cantilever. Based on the hypothesis that the near-surface region of a continuum is subject to the extra stress, thin surface and interface layers are introduced to our model. The thin layer is subject to an axial force exerted by the extra stress, which in turn affects the transverse vibration of the cantilever. We tested the analytical model by varying the interfacial tension between the silicon nitride microchannel cantilever and the filled alkanes, whose interfacial tension varies with chain length. Compared with the conventional Euler-Bernoulli model, our enhanced model provides a better agreement to the experimental results, shedding light on precision measurements using micro-sized cantilever resonators.

Hearing loss is a genetically heterogeneous disorder affecting approximately 360 million people worldwide and is among the most common sensorineural disorders. Here, we report a genetic analysis of seven large consanguineous families segregating prelingual sensorineural hearing loss. Whole-exome sequencing (WES) revealed seven different pathogenic variants segregating with hearing loss in these families, three novel variants (c.1204G>A, c.322G>T, and c.5587C>T) in TMPRSS3, ESRRB, and OTOF , and four previously reported variants (c.208C>T, c.6371G>A, c.226G>A, and c.494C>T) in LRTOMT , MYO15A , KCNE1 , and LHFPL5 , respectively . All identified variants had very low frequencies in the control databases and were predicted to have pathogenic effects on the encoded proteins. In addition to being familial, we also found intersibship locus heterogeneity in the evaluated families. The known pathogenic c.226C>T variant identified in KCNE1 only segregates with the hearing loss phenotype in a subset of affected members of the family GCNF21. This study further highlights the challenges of identifying disease-causing variants for highly heterogeneous disorders and reports the identification of three novel and four previously reported variants in seven known deafness genes., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Diabetes mellitus is a life threatening disease and scientists are doing their best to find a cost effective and permanent treatment of this malady. The recent trend is to control the disease by target base inhibiting of enzymes or proteins. Secreted frizzled-related protein 4 (SFRP4) is found to cause five times more risk of diabetes when expressed above average levels. This study was therefore designed to analyze the SFRP4 and to find its potential inhibitors. SFRP4 was analyzed by bio-informatics tools of sequence tool and structure tool. A total of three potential inhibitors of SFRP4 were found, namely cyclothiazide, clopamide and perindopril. These inhibitors showed significant interactions with SFRP4 as compared to other inhibitors as well as control (acetohexamide). The findings suggest the possible treatment of diabetes mellitus type 2 by inhibiting the SFRP4 using the inhibitors cyclothiazide, clopamide and perindopril.