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Protein Kinase C alpha (PKCα) is a critical signaling molecule that plays a crucial role in various physiological processes, including cell growth, differentiation, and survival. Over the years, there has been a growing interest in targeting PKCα as a promising drug target for the treatment of various diseases, including cancer. Targeting PKCα can, therefore, serve as a potential strategy to prevent cancer progression and enhance the efficacy of conventional anticancer therapies. We conducted a systematic search for promising compounds for their anticancer potential that target PKCα using natural compounds from the IMPPAT database. The initial compounds were screened through various tests, including analysis of their physical and chemical properties, PAINS filter, ADMET analysis, PASS analysis, and specific interaction analysis. We selected those that showed high binding affinity and specificity to PKCα from the screened compounds, and we further analyzed them using molecular dynamics simulations (MDS) and principal component analysis (PCA). Various systematic parameters from the MDS analyses suggested that the protein-ligand complexes were stabilized throughout the simulation trajectories of 100 nanoseconds (ns). Our findings indicated that compounds Nicandrenone and Withaphysalin D bind to PKCα with high stability and affinity, making them potential candidates for further research in cancer therapeutics innovation in clinical contexts.Communicated by Ramaswamy H. Sarma.

Tyrosine-protein kinase BLK, also known as B-cell lymphocyte kinase (BLK), is a non-receptor tyrosine kinase that is primarily expressed in B-cells. BLK plays a key role in B-cell signaling, particularly in B-cell development and maturation. The increased expression of BLK has been linked to various complex diseases, including autoimmune disorders, and specific malignancies of B cells, such as lymphomas and leukemias. Due to its significant involvement in B-cell signaling, BLK has emerged as a promising target for drug development, offering the potential for developing novel therapeutics to combat these diseases. Small molecule inhibitors of BLK hold great potential for therapeutic intervention; however, discovering potent and selective inhibitors remains challenging. Within this context, natural compounds hold significant potential as a valuable resource for discovering novel inhibitors of BLK. In the current study, a structure-based virtual screening of the IMPPAT 2 library was employed to identify promising candidates with potential as inhibitors of BLK. The control molecule for this study was the known BLK inhibitor, Dasatinib. After a multi-step filtering process, two molecules (Withanolide I and Mexogenin) demonstrated potential against BLK based on their superior binding affinity, ligand efficiency, and specific interaction. Interaction analysis of these compounds revealed several significant interactions with the active site residues of BLK. Both proposed molecules remained bound to the binding pocket of BLK, as indicated by the molecular dynamics (MD) simulation study. Taken together, these findings provide valuable insights for guiding future research endeavors and translational efforts in developing therapeutics for different complex diseases, such as autoimmune disorders, lymphomas, and leukemias.Communicated by Ramaswamy H. Sarma.

The application of gold nanoparticles (AuNPs) in cancer therapy, particularly targeted therapy of glioblastoma multiforme (GBM), is an up-and-coming field of research that has gained much interest in recent years. GBM is a life-threatening malignant tumour of the brain that currently has a 95 % death rate with an average of 15 months of survival. AuNPs have proven to have wide clinical implications and compelling therapeutic potential in many researches, specifically in GBM treatment. It was found that the reason why AuNPs were highly desired for GBM treatment was due to their unique properties that diversified the applications of AuNPs further to include imaging, diagnosis, and photothermal therapy. These properties include easy synthesis, biocompatibility, and surface functionalization. Various studies also underscored the ability of AuNPs to cross the blood-brain-barrier and selectively target tumour cells while displaying no major safety concerns which resulted in better therapy results. We attempt to bring together some of these studies in this review and provide a comprehensive overview of safety evaluations and current and potential applications of AuNPs in GBM therapy that may result in AuNP-mediated therapy to be the new gold standard for GBM treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hypopharyngeal cancer is a disease that is associated with EGFR-mutated lung adenocarcinoma. Here we utilized a bioinformatics approach to identify genetic commonalities between these two diseases. To this end, we examined microarray datasets from GEO (Gene Expression Omnibus) to identify differentially expressed genes, common genes, and hub genes between the selected two diseases. Our analyses identified potential therapeutic molecules for the selected diseases based on 10 hub genes with the highest interactions according to the degree topology method and the maximum clique centrality (MCC). These therapeutic molecules may have the potential for simultaneous treatment of these diseases., (© 2024 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The discovery of novel therapeutic agents with potent anticancer activity remains a critical challenge in drug development. Natural products, particularly bioactive phytoconstituents derived from plants, have emerged as promising sources for anticancer drug discovery. In this study, we used virtual screening techniques to explore the potential of bioactive phytoconstituents as inhibitors of fibroblast growth factor receptor 1 (FGFR1), a key signaling protein implicated in cancer progression. We used virtual screening techniques to analyze phytoconstituents extracted from the IMPPAT 2.0 database. Our primary objective was to discover promising inhibitors of FGFR1. To ensure the selection of promising candidates, we initially filtered the molecules based on their physicochemical properties. Subsequently, we performed binding affinity calculations, PAINS, ADMET, and PASS filters to identify nontoxic and highly effective hits. Through this screening process, one phytocompound, namely Mundulone, emerged as a potential lead. This compound demonstrated an appreciable affinity for FGFR1 and exhibited specific interactions with the ATP-binding site residues. To gain further insights into the conformational dynamics of Mundulone and the reference FGFR1 inhibitor, Lenvatinib, we conducted time-evolution analyses employing 200 ns molecular dynamics simulations (MDS) and essential dynamics. These analyses provided valuable information regarding the dynamic behavior and stability of the compounds in complexes with FGFR1. Overall, the findings indicate that Mundulone exhibits promising binding affinity, specific interactions, and favorable drug profiles, making it a promising lead candidate. Further experimental analysis will be necessary to confirm its effectiveness and safety profiles for therapeutic advancement in the cancer field.Communicated by Ramaswamy H. Sarma.

Sortilin (SORT1) is a multifunctional protein intricately involved in atherogenesis, coronary artery disease (CAD), and various neurological disorders. It has materialized as a potential pharmacological target for therapeutic development due to its diverse biological roles in pathological processes. Despite its central role under these conditions, effective therapeutic strategies targeting SORT1 remain challenging. In this study, we introduce a drug repurposing strategy guided by structural insights to identify potent SORT1 inhibitors with broad therapeutic potential. Our approach combines molecular docking, virtual screening, and molecular dynamics (MD) simulations, enabling the systematic evaluation of 3648 FDA-approved drugs for their potential to modulate SORT1. The investigation reveals a subset of repurposed drugs exhibiting highly favorable binding profiles and stable interactions within the binding site of SORT1. Notably, two hits, ergotamine and digitoxin, were carefully chosen based on their drug profiles and subjected to analyze their interactions with SORT1 and stability assessment via all-atom MD simulations spanning 300 ns (ns). The structural analyses uncover the complex binding interactions between these identified compounds and SORT1, offering essential mechanistic insights. Additionally, we explore the clinical implications of repurposing these compounds as potential therapeutic agents, emphasizing their significance in addressing atherogenesis, CAD, and neurological disorders. Overall, this study highlights the efficacy of structure-guided drug repurposing and provides a solid foundation for future research endeavors aimed at the development of effective therapies targeting SORT1 under diverse pathological conditions., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Hematopoietic cell kinase (HCK) has emerged as a potential target for therapeutic intervention in cancer and HIV infection because of its critical role in critical signaling pathways. Repurposing FDA-approved drugs offers an efficient strategy to identify new treatment options. Here, we address the need for novel therapies in cancer and HIV by investigating the potential of repurposed drugs against HCK. Our goal was to identify promising drug candidates with high binding affinities and specific interactions within the HCK binding pocket. We employed an integrated computational approach combining molecular docking and extensive molecular dynamics (MD) simulations. Initially, we analyzed the binding affinities and interaction patterns of a library of FDA-approved drugs sourced from DrugBank. After careful analysis, we focused on two compounds, Nilotinib and Radotinib, which exhibit exceptional binding affinities and specificity to the HCK binding pocket, including the active site. Additionally, we assessed the pharmacological properties of Nilotinib and Radotinib, making them attractive candidates for further drug development. Extensive all-atom MD simulations spanning 200 nanoseconds (ns) elucidated the conformational dynamics and stability of the HCK-Nilotinib and HCK-Radotinib complexes. These simulations demonstrate the robustness of these complexes over extended timescales. Our findings highlighted the potential of Nilotinib and Radotinib as promising candidates against HCK that offer valuable insights into their binding mechanisms. This computational approach provides a comprehensive understanding of drug interactions with HCK and sets the stage for future experimental validation and drug development endeavors.Communicated by Ramaswamy H. Sarma.

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC., (© 2024 John Wiley & Sons Ltd.)

Background: Congenital anomalies, representing structural or functional abnormalities present at birth, pose a substantial global health challenge, affecting 8 million newborns annually. With 3.3 million succumbing before age five and 3.2 million facing physical or mental disability, their diverse causes necessitate comprehensive understanding for effective healthcare planning. This study explores the prevalence of congenital anomalies among newborns in the Abha Maternity and Children Hospital (MCH) in Abha, Kingdom of Saudi Arabia. Methodology: A descriptive cross-sectional record-based study was conducted on newborns born between 2018 and 2022. Data were gathered in 4 months from September to December 2023. Purposive sampling was employed to select the case records of newborns with congenital anomalies after careful screening and considering inclusion and exclusion criteria. Data was acquired through a self-designed study tool, and the data were entered into Google Forms. Results: Congenital anomalies' five-year prevalence was 3.21%, and one year, in 2022, the prevalence was 4.02%. Female neonates exhibited higher anomalies (59.3%), and preterm births accounted for 39.6%, emphasizing their vulnerability. The findings indicate that consanguineous marriages are linked to 63.3% of anomalies, notably neural tube defects (25%) and congenital heart diseases (19.7%). Anomalies are not significantly associated with consanguinity or birth order, but maternal age, education, employment, and antenatal maternal medical issues are associated considerably. Conclusions: These study insights contribute to health planners planning targeted interventions and awareness programs that are crucial to mitigate risks associated with preterm births and consanguineous marriages. The promotion of 100% antenatal screening and prophylactic medication for high-risk women and couples is necessary to prevent inherited deformities. In future the Ministry of Health must plan large-group prospective research to better understand the associated risk factors that will help public health initiatives minimize congenital-associated neonatal mortality and improve pregnancy outcomes.

Cancer is a significant global health concern that has a major impact on morbidity and mortality worldwide. Research has demonstrated the involvement of Interleukin-1 beta (IL1β) in various aspects of cancer development and progression, including angiogenesis, tumor growth and metastasis. Consequently, targeting IL1β activity represents a promising approach for cancer therapeutics. In this study, we utilized molecular docking and MD simulations to discover potent IL1β inhibitors for the treatment of cancer. Five thousand compounds from ZINC15 database were screened against IL1β target, and the top ten small molecules were selected based on their binding energy. The small molecule named 'ZINC08101049' was prioritized based on binding energy (-9.1 kcal/Mol) and residual interaction specifically forming seven hydrogen bonds with amino acid residues namely GLN81, GLY136, LEU134, LYS138, SER84, THR137 and TYR24 of IL1β. Next, IL1β alone and in complex with ZINC08101049 was subjected to MD simulations to determine their behavior at atomic level. The results of molecular docking and MD simulation revealed ZINC08101049 as a potential inhibitor of IL1β, reflecting that ZINC08101049 can emerge as a promising small molecule paving for cancer therapeutics.Communicated by Ramaswamy H. Sarma.

Dihydrofolate reductase (DHFR) has gained significant attention in drug development, primarily due to marked distinctions in its active site among different species. DHFR plays a crucial role in both DNA and amino acid metabolism by facilitating the transfer of monocarbon residues through tetrahydrofolate, which is vital for nucleotide and amino acid synthesis. This considers its potential as a promising target for therapeutic interventions. In this study, our focus was on conducting a virtual screening of phytoconstituents from the IMPPAT2.0 database to identify potential inhibitors of DHFR. The initial criterion involved assessing the binding energy of molecules against DHFR and we screened top 20 compounds ranging energy -13.5 to -11.4 (kcal/Mol) while Pemetrexed disodium bound with less energy -10.2 (kcal/Mol), followed by an analysis of their interactions to identify more effective hits. We prioritized IMPHY007679 ( Bismurrayaquinone-A ), which displayed a high binding affinity and crucial interaction with DHFR. We also evaluated the drug-like properties and biological activity of IMPHY007679. Furthermore, MD simulation was done, RMSD, RMSF, Rg, SASA, PCA and FEL explore the time-evolution impact of IMPHY007679 comparing it with a reference drug, Pemetrexed disodium. Collectively, our findings suggest that IMPHY007679 recommend further investigation in both in vitro and in vivo settings for its potential in developing anticancer and antibacterial therapies. This compound holds promise as a valuable candidate for advancing drug research and treatment strategies.Communicated by Ramaswamy H. Sarma.

It is becoming more and more apparent that many of the genetic alterations associated with cancer are located in areas that do not encode proteins. lncRNAs are a class of RNAs that do not code for proteins but play a crucial role in maintaining cell function and regulating various cellular processes. By doing this, they have recently introduced what may be a brand-new and essential layer of biological control. These have more than 200 nucleotides and are linked to several diseases; as a result, they have become potential tools for therapeutic intervention. Emerging technologies suggest the presence of mutations on genomic loci that give rise to lncRNAs rather than proteins in a disease as complex as cancer. These lncRNAs play essential parts in gene regulation, which impacts several cellular homeostasis processes, including proliferation, survival, migration, and genomic stability. The leading cause of death in the world today is cancer. Delays in diagnosis and a lack of standard and efficient treatments are the leading causes of the high death rate. Clinically, surgery is frequently used successfully to remove cancers that have not spread, but it is less successful in treating metastatic cancer, which has a drastically lower chance of survival. Chemotherapeutic drugs are a typical therapy to treat the cancer that has spread to other organs. Drug resistance to chemotherapy, however, presents a significant challenge to achieving positive outcomes and is frequently the cause of treatment failure. A substantial barrier to progress in medical oncology is cancer drug resistance. Resistance can develop clinically either before or after cancer treatment. According to this study, lncRNAs influence drug resistance through several different methods. LncRNAs often impact drug resistance by controlling the expression of a few intermediary regulatory variables rather than by directly affecting drug resistance. Additionally, lncRNAs have a variety of roles in cancer medication resistance. Most lncRNAs induce drug resistance when overexpressed; however, other lncRNAs have inhibitory effects. This study provides an overview of the current understanding of lncRNAs, relevance to cancer, and potential therapeutic applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

Within the realm of soluble factors that have emerged as potential targets for therapeutic intervention, the chemokine interleukin-8 (IL-8) has garnered attention as a potential contributor to treatment responses in various cancer types. The utilization of naturally occurring anticancer compounds for treating cancer patients has shown substantial advancements in survival rates across early and advanced stages of the disease. In silico research findings provide support for the application of phytochemicals as potential inhibitors of IL-8, and phytochemicals exhibiting a high binding free energy and crucial interactions display promising anticancer properties, positioning them as candidates for future drug development. Noteworthy phytochemicals such as IMPHY006634 (Isohydnocarpin), IMPHY007957 (Chitranone) and IMPHY013015 (1-Hydroxyrutaecarpine) were predicted to possess inhibitory activity against IL-8, with calculated energies ranging from -9.9 to -9.1 kcal/mol, respectively. Several hydrogen bonds, including common amino acid residues Lys9 and CYS48, were identified. Molecular dynamics calculations conducted on these potent inhibitors demonstrated their stability throughout a 200 ns simulation, as indicated by metrics such as RMSD, RMSF, Rg, SASA, H-bonds, PCA and FEL analysis. Moreover, PASS analysis and adherence of these natural compounds to drug-likeness rules like Lipinski's further strengthen their candidacy. Considering these calculations and various parameters, these three prominent natural compounds emerge as promising candidates for anti-IL-8 therapy in the management of cancer.Communicated by Ramaswamy H. Sarma.

High blood sugar and insulin insensitivity causes the lifelong chronic metabolic disease called Type 2 diabetes (T2D) which has a higher chance of developing different malignancies. T2D with comorbidities like Cancers can make normal medications for those disorders more difficult. There may be a significant correlation between comorbidities and have an impact on one another's health. These associations may be due to a number of direct and indirect mechanisms. Such molecular mechanisms that underpin T2D and cancer are yet unknown. However, the large volumes of data available on these diseases allowed us to use analytical tools for uncovering their interrelated pathways. Here, we tried to present a system for investigating potential comorbidity relationships between T2D and Cancer disease by looking at the molecular processes involved, analyzing a huge number of freely accessible transcriptomic datasets of various disorders using bioinformatics. Using semantic similarity and gene set enrichment analysis, we created an informatics pipeline that evaluates and integrates Gene Ontology (GO), expression of genes, and biological process data. We discovered genes that are common in T2D and Cancer along with molecular pathways and GOs. We compared the top 200 Differentially Expressed Genes (DEGs) from each selected T2D and cancer dataset and found the most significant common genes. Among all the common genes 13 genes were found most frequent. We also found 4 common GO terms: GO:0000003, GO:0000122, GO:0000165, and GO:0000278 among all the common GO terms between T2d and different cancers. Using these genes and GO term semantic similarity, we calculated the distance between these two diseases. The semantic similarity results of our study showed a higher association of Liver Cancer (LiC), Breast Cancer (BreC), Colorectal Cancer (CC), and Bladder Cancer (BlaC) with T2D. Furthermore we found KIF4A, NUSAP1, CENPF, CCNB1, TOP2A, CCNB2, RRM2, HMMR, NDC80, NCAPG, and IGFBP5 common hub proteins among different cancers correlated to T2D. AGE-RAGE signaling pathway in diabetic complications, Osteoclast differentiation, TNF signaling pathway, IL-17 signaling pathway, p53 signaling pathway, MAPK signaling pathway, Human T-cell leukemia virus 1 infection, and Non-alcoholic fatty liver disease are the 8 most significant pathways found among 18 common pathways between T2D and selected cancers. As a result of our technique, we now know more about disease pathways that are critical between T2D and cancer., Competing Interests: Declaration of competing interest This research was supported by the Deanship of Scientific Research Large Groups at King Khalid University, Kingdom of Saudi Arabia (RGP.2/219/43)., (Copyright © 2023. Published by Elsevier Inc.)

Current genome-wide studies have indicated that a great number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and appeared as crucial regulators in a variety of cellular processes. Many studies have displayed a significant function of lncRNAs in the regulation of autophagy. Autophagy is a macromolecular procedure in cells in which intracellular substrates and damaged organelles are broken down and recycled to relieve cell stress resulting from nutritional deprivation, irradiation, hypoxia, and cytotoxic agents. Autophagy can be a double-edged sword and play either a protective or a damaging role in cells depending on its activation status and other cellular situations, and its dysregulation is related to tumorigenesis in various solid tumors. Autophagy induced by various therapies has been shown as a unique mechanism of resistance to anti-cancer drugs. Growing evidence is showing the important role of lncRNAs in modulating drug resistance via the regulation of autophagy in a variety of cancers. The role of lncRNAs in drug resistance of cancers is controversial; they may promote or suppress drug resistance via either activation or inhibition of autophagy. Mechanisms by which lncRNAs regulate autophagy to affect drug resistance are different, mainly mediated by the negative regulation of micro RNAs. In this review, we summarize recent studies that investigated the role of lncRNAs/autophagy axis in drug resistance of different types of solid tumors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Leishmaniasis is one of the most neglected parasitic diseases worldwide. The toxicity of current drugs used for its treatment is a major obstacle to their effectiveness, necessitating the discovery and development of new therapeutic agents for better disease control. In Leishmania parasites, N-Myristoyltransferase (NMT) has been identified as a promising target for drug development. Thus, exploring well-known medicinal plants such as Azadirachta indica and their phytochemicals can offer a diverse range of treatment options, potentially leading to disease prevention and control. To assess the therapeutic potential of these compounds, their ADMET prediction and drug-likeness properties were analyzed. The top 4 compounds were selected which had better and significantly low binding energy than the reference molecule QMI. Based on the binding energy score of the top compounds, the results show that Isonimocinolide has the highest binding affinity (-9.8 kcal/mol). In addition, a 100 ns MD simulation of the four best compounds showed that Isonimocinolide and Nimbolide have good stability with LmNMT. These compounds were then subjected to MMPBSA (last 30 ns) calculation to analyze protein-ligand stability and dynamic behavior. Nimbolide and Meldenin showed lowest binding free energy i.e. -84.301 kJ/mol and -91.937 kJ/mol respectively. DFT was employed to calculate the HOMO-LUMO energy gap, global reactivity parameters, and molecular electrostatic potential of all hit molecules. The promising results obtained from MD simulations and MMPBSA analyses provide compelling evidence for the potential use of these compounds in future drug development efforts for the treatment of leishmaniasis.Communicated by Ramaswamy H. Sarma.

Leucine-rich repeat kinase 2 (LRRK2) is a promising drug target for the therapeutic management of Parkinson's disease (PD) and other neurodegenerative disorders. LRRK2 inhibitors have the potential to modulate neuroinflammation, reduce alpha-synuclein aggregation and improve motor symptoms in PD patients. Although LRRK2 inhibitors are still in the early stages of clinical development, the identification of potent and selective inhibitors through structure-guided approaches provides a promising avenue for the development of effective therapies for PD and other neurodegenerative disorders. In this study, natural compounds from the IMPPAT database were screened using a state-of-the-art computational virtual screening approach to identify potential inhibitors of LRRK2. We carried out a docking screening on a library of natural compounds and identified a few compounds with strong binding affinity, docking score and specificity towards LRRK2 as the top hits. These hits were then subjected to further analysis based on multiple parameters for the Pan-assay interference compounds and their physicochemical and pharmacokinetics evaluation followed by a detailed interaction analysis. After careful evaluation, one natural compound, Panicutine, was identified as a promising candidate for LRRK2 due to its significant affinity and specificity towards the LRRK2 binding pocket. Additionally, it exhibited drug-like properties with blood-brain barrier permeability as determined by ADMET properties. To gain a deeper understanding of the stability and conformational changes of the LRRK2-ligand complex, MD simulations were conducted for 100 nanoseconds under explicit solvent conditions followed by principal component analysis and free energy dynamics. The simulation results demonstrated that the LRRK2-Panicutine complex remained stable throughout the simulation trajectories. Based on these findings, it is concluded that Panicutine has the potential to act as a LRRK2 inhibitor against PD and other neurodegenerative disorders.Communicated by Ramaswamy H. Sarma.

Simultaneous estimation of folic acid and methotrexate in bulk and tablet dosage form by RP-HPLC-PDA was conducted via Box‒Behnken design application. Three-factor numerical values were finalized from the graphical and numerical optimization with built-in ANOVA in BBD. Sharp and symmetric peaks were observed at 4.138 and 6.929 min for folic acid and methotrexate, respectively. The mobile phase composition was methanol and 0.1% formic acid in water with a ratio of 31:69 and a flow rate of 1.1 ml/min. Both drugs were detected at a wavelength of 291 nm. The developed method was validated according to ICH guidelines. The results of the validation parameters were within acceptable limits. Stress stability studies have been performed under acidic, alkali, oxidation, neutral and photolytic conditions. Three different brand-marketed tablets were assessed with the developed method (MGXT, FOLTNAX and TRUXOFOL). In the tablet formulations, chromatogram percentages of folic acid and methotrexate were calculated at 99.13% and 99.50 in MGXT, 99.17% and 99.47 in FOLTNAX, and 99.91 and 100.05 in TRUXOFOL., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Biomarker-based cancer identification and classification tools are widely used in bioinformatics and machine learning fields. However, the high dimensionality of microarray gene expression data poses a challenge for identifying important genes in cancer diagnosis. Many feature selection algorithms optimize cancer diagnosis by selecting optimal features. This article proposes an ensemble rank-based feature selection method (EFSM) and an ensemble weighted average voting classifier (VT) to overcome this challenge. The EFSM uses a ranking method that aggregates features from individual selection methods to efficiently discover the most relevant and useful features. The VT combines support vector machine, k-nearest neighbor, and decision tree algorithms to create an ensemble model. The proposed method was tested on three benchmark datasets and compared to existing built-in ensemble models. The results show that our model achieved higher accuracy, with 100% for leukaemia, 94.74% for colon cancer, and 94.34% for the 11-tumor dataset. This study concludes by identifying a subset of the most important cancer-causing genes and demonstrating their significance compared to the original data. The proposed approach surpasses existing strategies in accuracy and stability, significantly impacting the development of ML-based gene analysis. It detects vital genes with higher precision and stability than other existing methods.

Mechanistic target of rapamycin (mTOR) is a protein kinase that regulates cellular growth, development, survival, and metabolism through integration of diverse extracellular and intracellular stimuli. Additionally, mTOR is involved in interplay of signalling pathways that regulate apoptosis and autophagy. In cells, mTOR is assembled into two complexes, mTORC1 and mTORC2. While mTORC1 is regulated by energy consumption, protein intake, mechanical stimuli, and growth factors, mTORC2 is regulated by insulin-like growth factor-1 receptor (IGF-1R), and epidermal growth factor receptor (EGFR). mTOR signalling pathways are considered the hallmark in cancer due to their dysregulation in approximately 70% of cancers. Through downstream regulators, ribosomal protein S6 kinase β-1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), mTORC1 influences various anabolic and catabolic processes in the cell. In recent years, several mTOR inhibitors have been developed with the aim of treating different cancers. In this review, we will explore the current developments in the mTOR signalling pathway and its importance for being targeted by various inhibitors in anti-cancer therapeutics.

More research is needed to understand the benefits of environmentally safe and human-friendly herbal-based sunscreen agents against ultraviolet (UV) radiation. Because of the toxicity of synthetic chemicals in photoprotective agents, researchers were increasingly focusing on herbal photoprotective formulations. The photoprotective agent's skin retention can be considerably improved by forming solid lipid nanoparticles (SLN). The study's objective is to evaluate the photoprotective potential of sunscreen cream containing spinach (Spinacia oleracea)-loaded SLN. A solvent emulsification technique was used to develop the spinach-loaded SLN. The various characterization techniques of the developed SLN were performed. Out of all the formulations, the optimized one was fitted into cream and estimated for its photoprotective action. The images obtained from scanning electron microscopy (SEM) revealed the morphological characteristics of the prepared SLN. The sunscreen cream's viscosity, spreadability, extrudability, and release rate were within acceptable limits. The formulation's in vitro and in vivo sun protection factor (SPF) was reported to be 15.9 and 14.75, respectively. The results indicated that the prepared formulation possesses good photoprotective action. The accelerated stability tests were carried out with no noticeable changes in the parameters. Our work demonstrated the possibility of using spinach-loaded SLN as a photoprotective agent in cosmetic formulations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chalcones with methoxy substituent are considered as a promising framework for the inhibition of monoamine oxidase (MAO) enzymes., Methods: A series of nine trimethoxy substituted chalcones (TMa-TMi) was synthesized and evaluated as a multifunctional class of MAO inhibitors. All the synthesized compounds were investigated for their in vitro MAO inhibition, kinetics, reversibility, blood-brain barrier (BBB) permeation, and cytotoxicity and antioxidant potentials., Results: In the present study, compound (2E)-3-(4-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)prop- 2-en-1-one (TMf) was provided with a MAO-A inhibition constant value equal to 3.47±0.09 μM with a selectivity of 0.008, thus comparable to that of moclobemide, a well known potent hMAOA inhibitor (SI=0.010). Compound (2E)-3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2- en-1-one (TMh) show good MAO-B inhibition with inhibition constant of 0.46±0.009 μM. The PAMPA assay demonstrated that all the synthesized derivatives can cross the BBB successfully. The cytotoxicity studies revealed that TMf and TMh have 88.22 and 80.18 % cell viability at 25 μM. Compound TMf appeared as the most promising antioxidant molecule with IC 50 values, relative to DPPH and H 2 O 2 radical activities equal to 6.02±0.17 and 7.25±0.07 μM. To shed light on the molecular interactions of TMf and TMh towards MAO-A and MAO-B, molecular docking simulations and MM/GBSA calculations have been carried out., Conclusion: The lead molecules TMf and TMh with multi-functional nature can be further employed for the treatment of various neurodegenerative disorders and depressive states., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Parkinson's disease is a progressive neurodegenerative disorder that affects mostly elderly people above the age of 60. Previously, we have reported that the ethoxylated chalcone derivative (E)-1-(4-ethoxyphenyl)-3-(fluorophenyl)prop-2-en-1-one (E7) showed potent, reversible, and competitive MAO-B inhibition with an IC 50 value of 0.053 μm. The present study aims to investigate the anti-Parkinson activity of compound E7 in a haloperidol-induced animal model of mice. The disease was induced with haloperidol (1 mg/kg, intraperitoneal route) once daily for 21 days. E7 was given at dose levels of 10, 20, and 30 mg/kg/day for 21 days, consecutively. Behavioural tests were carried out during and at the end of the study. Biochemical analyses such as oxidative stress biomarkers and neurotransmitters were quantified on the brain homogenate at the end of the study. Behavioural results showed that there is a marked improvement in locomotor activity and motor coordination in the treatment group. Oxidative stress biomarkers such as SOD, CAT, and GSH levels were increased dose-dependently with a maximum at 30 mg/kg, whereas the dose-dependent decrease (30 mg/kg) in the MDA and nitrite levels were observed in the treatment groups. Levels of neurotransmitters, such as dopamine, serotonin, and noradrenaline, were increased in the treatment groups while dopamine and noradrenaline levels were more than in the standard treated group. MAO-B level was also decreased dose dependently in the treatment group in comparison with the control group. Based on the findings, it was concluded that the E7 compound exhibited anti-Parkinson activity which was more evident at 30 mg/kg oral dose as evaluated by the haloperidol-induced animal model of mice., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)