Therapeutic potential of Buddleja Polystachya Fresen (stem and leaves) extracts: antimicrobial and cytotoxic properties for ocular disease management.

This study on Buddleja polystachya highlights its phytochemical composition, antimicrobial activity, and cytotoxic impacts. The study emphasizes the plant's potential to treat ocular diseases by identifying important compounds involved in the bioactivity through GC-MS analysis. This study explores the antimicrobial and cytotoxic potential of Buddleja polystachya (stem and leaves) extracts, with a focus on their application in treating bacterial ocular infections and their efficacy against MCF7, HT29, and HepG2 cancer cells. Through comprehensive GC-MS analysis, a diverse array of phytochemicals was identified within Buddleja polystachya stem and leaves extracts, including carbohydrates, phenolic derivatives, fatty acids, and steroidal components. The extracts were then evaluated for their biological activities, revealing significant antimicrobial properties against a range of bacterial strains implicated in ocular infections. The research findings demonstrate that stem extracts derived from Buddleja polystachya demonstrated high to moderate cytotoxic effects on cancer cell lines MCF7, HT29, and HepG2. Notably, these effects were characterized by varying IC50 values, which suggest distinct levels of sensitivity. In contrast, leaf extracts exhibited reduced cytotoxicity when tested against all these cell lines, although they did so with a significantly higher cytotoxicity aganist HepG2 cells. The results of this investigation highlight the potential therapeutic utilization of Buddleja polystachya extracts in the management of ocular infections and cancer. These results support the need for additional research to elucidate the underlying mechanisms of action of these extracts and explore their potential as drugs.

Initial report on the multiple biological and pharmacological properties of hispolon: Exploring stochastic mechanisms.

The development of natural substances derived from nature poses a significant challenge as technologies for the extraction and characterization of active principles advance. Hispolon has received a lot of attention in recent years, ascribable to its wide range of biological activities. It is a phenolic molecule that was extracted from several mushroom species such as Phellinus igniarius, Phellinus linteus, Phellinus lonicerinus, Phellinus merrillii, and Inonotus hispidus. To provide a comprehensive overview of the pharmacological activities of hispolon, this review highlights its anticancer, anti-inflammatory, antioxidant, antibacterial, and anti-diabetic activities. Several scientific research databases, including Google Scholar, Web of Science, PubMed, SciFinder, SpringerLink, Science Direct, Scopus, and, Wiley Online were used to gather the data on hispolon until May 2024. The in vitro and in vivo studies have revealed that hispolon exhibited significant anticancer properties through modifying several signaling pathways including cell apoptosis, cycle arrest, autophagy, and inhibition of angiogenesis and metastasis. Hispolon's antimicrobial activity was proven against many bacterial, fungal, and viral pathogens, highlighting its potential use as a novel antimicrobial agent. Additionally, hispolon displayed potent anti-inflammatory activity through the suppression of key inflammatory mediators, such as inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), and cyclooxygenases-2 (COX-2), and the modulation of mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. The antioxidant potential of hispolon was attributed to its capacity to neutralize reactive oxygen species (ROS) and to increase the activity of antioxidant enzymes, indicating a possible involvement in the prevention of oxidative stress-related illnesses. Hispolon's antidiabetic activity was associated with the inhibition of aldose reductase and α-glucosidase. Studies on hispolon emphasized its potential use as a promising scaffold for the development of novel therapeutic agents targeting various diseases, including cancer, infectious diseases, inflammatory disorders, and diabetes.

Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances pro-apoptotic factors while decreasing anti-apoptotic factors. Additionally, it regulates the immune response by up-regulating programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression, and can impact proteasome and/or aggresome degradation, endoplasmic reticulum function, cell cycle arrest, apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this study, we sought to elucidate the precise molecular mechanism by which Vorinostat inhibits HDACs. A deeper understanding of these mechanisms could improve our understanding of cancer cell abnormalities and provide new therapeutic possibilities for cancer treatment.

Recent advances and molecular mechanisms of TGF-ß signaling in colorectal cancer, with focus on bioactive compounds targeting.

Colorectal cancer (CRC) is one of the most significant forms of human cancer. It is characterized by its heterogeneity because several molecular factors are involved in contiguity and can link it to others without having a linear correlation. Among the factors influencing tumor transformation in CRC, transforming growth factor-beta (TGF-ß) plays a key promoter role. This factor is associated with human colorectal tumors with a very high prognosis: it increases the survival, invasion, and metastasis of CRC cells, thus functioning as an oncogene. The inhibition of this factor can constitute a major therapeutic route for CRC treatment. Various chemical drugs including synthetic molecules and biotherapies have been developed as TGF-ß inhibitors. Moreover, the scientific community has recently shown a major interest in screening natural drugs inhibiting TGF-ß in CRC. In this context, we carried out this review article using computerized databases, such as PubMed, Google Scholar, Springer Link, Science Direct, Cochrane Library, Embase, Web of Science, and Scopus, to highlight the molecular mechanism of TGF-ß in CRC induction and progression and current advances in the pharmacodynamic effects of natural bioactive substances targeting TGF-ß in CRC.

Precision arrows: Navigating breast cancer with nanotechnology siRNA.

Nanotechnology-based drug delivery systems, including siRNA, present an innovative approach to treating breast cancer, which disproportionately affects women. These systems enable personalized and targeted therapies, adept at managing drug resistance and minimizing off-target effects. This review delves into the current landscape of nanotechnology-derived siRNA transport systems for breast cancer treatment, discussing their mechanisms of action, preclinical and clinical research, therapeutic applications, challenges, and future prospects. Emphasis is placed on the importance of targeted delivery and precise gene silencing in improving therapeutic efficacy and patient outcomes. The review addresses specific hurdles such as specificity, biodistribution, immunological reactions, and regulatory approval, offering potential solutions and avenues for future research. SiRNA drug delivery systems hold promise in revolutionizing cancer care and improving patient outcomes, but realizing their full potential necessitates ongoing research, innovation, and collaboration. Understanding the intricacies of siRNA delivery mechanisms is pivotal for designing effective cancer treatments, overcoming challenges, and advancing siRNA-based therapies for various diseases, including cancer. The article provides a comprehensive review of the methods involved in siRNA transport for therapeutic applications, particularly in cancer treatment, elucidating the complex journey of siRNA molecules from extracellular space to intracellular targets. Key mechanisms such as endocytosis, receptor-mediated uptake, and membrane fusion are explored, alongside innovative delivery vehicles and technologies that enhance siRNA delivery efficiency. Moreover, the article discusses challenges and opportunities in the field, including issues related to specificity, biodistribution, immune response, and clinical translation. By comprehending the mechanisms of siRNA delivery, researchers can design and develop more effective siRNA-based therapies for various diseases, including cancer.

In-vitro Cytotoxicity Investigations for Phytoconstituents of Saudi Medicinal Plants With Putative Ocular Effects.

BACKGROUND: Metastatic secondary ocular tumors spread from systemic malignancies, including breast cancer. This study aimed to evaluate the cytotoxicity of extracts from 5 medicinal plants native to Saudi Arabia. METHODS: For preliminary activity screening, cytotoxicity using the MTT assay and selectivity index determinations were made for medicinal plant extracts against various cancer cell-lines. The most promising extract was subjected to GC-MS analysis to determine the phytochemical composition. Clonogenic assays were performed using the most promising extract to confirm the initial results. Finally, western blot analysis was used to determine the modulation in expression of survivin and P27 suppressor genes in the human breast adenocarcinoma (MCF7) cell-line to understand the potential mechanistic properties of the active plant extract. RESULTS: The 5 plant extracts showed various cytotoxic activity levels using IC50. The most active extract was found to be the leaves of Capparis spinosa L. (BEP-07 extract) against the MCF7 breast cancer cell-line (IC50 = 3.61 ± 0.99 µg/ml) and selectivity index of 1.17 compared to the normal human fetal lung fibroblast (MRC5) cells. BEP-07 extract showed a dose dependent clonogenic effect against the MCF7 colonies which was comparable with the effect of doxorubicin. BEP-07 extract caused a significant decrease of survivin and increase in P27 expression compared to control GAPDH at its highest dose (14 µg/ml). The GC-MS chromatogram of Capparis spinosa L. (BEP-07 extract) revealed the existence of 145 compounds, belonging to the diverse classes of phytoconstituents. Fatty acids and their derivatives represent 15.4%, whilst octadecanoic acid, 2,3-dihydroxypropyl ester was the principal component (7.9%) detected. CONCLUSION: Leaves of Capparis spinosa L. (BEP-07 extract) exhibited a significant cytotoxic effect particularly against breast cancer cells. It exhibited this effect through survivin inhibition and via P27 upregulation. The detected phytoconstituents in the plant extract might be involved in tested cytotoxic activity, while further investigations are required to complete the drug candidate profile.

Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase.

BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations. METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively. RESULTS: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 µM, 28.27 ± 1.52 µM, and 22.93 ± 1.63 µM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 µM). CONCLUSION: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

Pharmacological and Therapeutic Potential of Berbamine: A Potent Alkaloid from Genus Berberis.

Berbamine (Ber) is an active medicinal bisbenzylisoquinoline alkaloid, which is usually obtained from different plants of the genus Berberis (family Berberidaceae) and is used to cure various disorders in traditional Chinese and Ayurvedic systems of medicine. Numerous in-vitro and in-vivo studies revealed the apoptotic and cytotoxic potential of Ber against different cell lines (SMMC-7721, A549, MDA-MB-231, and K562) by upregulating pro-apoptotic (Bax, p53) and downregulating anti-apoptotic (Bcl-2, survivin) proteins. Other pharmacological attributes ascribed to Ber included cardioprotective, anti-diabetic, anti-inflammatory, antimalarial, antioxidant, anti-hypercholesterolemic, and anti-allergic. Moreover, the synergistic effect of Ber improved the therapeutic potential of different drugs (paclitaxel (PTL), gemcitabine, dexamethasone, doxorubicin (DOX), and celecoxib) in different models. Various attempts could fabricate biologically active derivatives of Ber, such as 4-chlorobenzoyl berbamine (CBB) and O-4- ethoxyl-butyl-berbamine (EBB). The review focuses on the medicinal applications of Ber, particularly anti-cancer, cardioprotective, and anti-inflammatory, along with the mechanism of action.

Chemistry, Biological Activities, and Pharmacological Properties of Gastrodin: Mechanism Insights.

Gastrodin, a bioactive compound derived from the rhizome of the orchid Gastrodia elata, exhibits a diverse range of biological activities. With documented neuroprotective, anti-inflammatory, antioxidant, anti-apoptotic, and anti-tumor effects, gastrodin stands out as a multifaceted therapeutic agent. Notably, it has demonstrated efficacy in protecting against neuronal damage and enhancing cognitive function in animal models of Alzheimer's disease, Parkinson's disease, and cerebral ischemia. Additionally, gastrodin showcases immunomodulatory effects by mitigating inflammation and suppressing the expression of inflammatory cytokines. Its cytotoxic activity involves the inhibition of angiogenesis, suppression of tumor growth, and induction of apoptosis. This comprehensive review seeks to elucidate the myriad potential effects of Gastrodin, delving into the intricate molecular mechanisms underpinning its pharmacological properties. The findings underscore the therapeutic potential of gastrodin in addressing various conditions linked to neuroinflammation and cancer.

Prospective virtual screening combined with bio-molecular simulation enabled identification of new inhibitors for the KRAS drug target.

Lung cancer is a disease with a high mortality rate and it is the number one cause of cancer death globally. Approximately 12-14% of non-small cell lung cancers are caused by mutations in KRASG12C. The KRASG12C is one of the most prevalent mutants in lung cancer patients. KRAS was first considered undruggable. The sotorasib and adagrasib are the recently approved drugs that selectively target KRASG12C, and offer new treatment approaches to enhance patient outcomes however drug resistance frequently arises. Drug development is a challenging, expensive, and time-consuming process. Recently, machine-learning-based virtual screening are used for the development of new drugs. In this study, we performed machine-learning-based virtual screening followed by molecular docking, all atoms molecular dynamics simulation, and binding energy calculations for the identifications of new inhibitors against the KRASG12C mutant. In this study, four machine learning models including, random forest, k-nearest neighbors, Gaussian naïve Bayes, and support vector machine were used. By using an external dataset and 5-fold cross-validation, the developed models were validated. Among all the models the performance of the random forest (RF) model was best on the train/test dataset and external dataset. The random forest model was further used for the virtual screening of the ZINC15 database, in-house database, Pakistani phytochemicals, and South African Natural Products database. A total of 100 ns MD simulation was performed for the four best docking score complexes as well as the standard compound in complex with KRASG12C. Furthermore, the top four hits revealed greater stability and greater binding affinities for KRASG12C compared to the standard drug. These new hits have the potential to inhibit KRASG12C and may help to prevent KRAS-associated lung cancer. All the datasets used in this study can be freely available at ( https://github.com/Amar-Ajmal/Datasets-for-KRAS ).

Bioactive compounds from nature: Antioxidants targeting cellular transformation in response to epigenetic perturbations induced by oxidative stress.

Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context.

Innovative Encapsulation Strategies for Food, Industrial, and Pharmaceutical Applications.

Bioactive metabolites obtained from fruits and vegetables as well as many drugs have various capacities to prevent or treat various ailments. Nevertheless, their efficiency, in vivo, encounter many challenges resulting in lower efficacy as well as different side effects when high doses are used resulting in many challenges for their application. Indeed, demand for effective treatments with no or less unfavorable side effects is rising. Delivering active molecules to a particular site of action within the human body is an example of targeted therapy which remains a challenging field. Developments of nanotechnology and polymer science have great promise for meeting the growing demands of efficient options. Encapsulation of active ingredients in nano-delivery systems has become as a vitally tool for protecting the integrity of critical biochemicals, improving their delivery, enabling their controlled release and maintaining their biological features. Here, we examine a wide range of nano-delivery techniques, such as niosomes, polymeric/solid lipid nanoparticles, nanostructured lipid carriers, and nano-emulsions. The advantages of encapsulation in targeted, synergistic, and supportive therapies are emphasized, along with current progress in its application. Additionally, a revised collection of studies was given, focusing on improving the effectiveness of anticancer medications and addressing the problem of antimicrobial resistance. To sum up, this paper conducted a thorough analysis to determine the efficacy of encapsulation technology in the field of drug discovery and development.

Polymorphism of HLA and Susceptibility of Breast Cancer.

Breast cancer (BC) is the second most common malignancy in the world. Numerous studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. The occurrence and development of BC are closely linked to genetic factors. Human leukocyte antigens G and E (HLA-G and HLA-E) are non-classical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting the cytotoxic and natural killer T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases, including tumors. The HLA system plays a key role in the escape of tumor cells from immune surveillance. This review aims to determine the correlation between BC susceptibility and HLA markers specific HLA alleles such as HLA-B07, HLA-DRB111, HLA-DRB113, and HLA-DRB115 are associated with an increased risk of developing BC. Furthermore, HLA-G mutations have been attributed to an elevated likelihood of metastasis in BC patients. Understanding the complex associations between the HLA system and BC development is critical for developing novel cancer prevention, detection, and treatment strategies. This review emphasizes the importance of analyzing HLA polymorphisms in the management of BC patients, as well as the urgent need for further research in this area.

Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies.

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs.

Computational insights into KRAS G12C inhibition: exploring possible repurposing of Azacitidine and Ribavirin.

Kirsten rat sarcoma (KRAS) stands out as the most prevalent mutated oncogene, playing a crucial role in the initiation and progression of various cancer types, including colorectal, lung and pancreatic cancer. The oncogenic modifications of KRAS are intricately linked to tumor development and are identified in 22% of cancer patients. This has spurred the necessity to explore inhibition mechanisms, with the aim of investigating and repurposing existing drugs for diagnosing cancers dependent on KRAS G12C In this investigation, 26 nucleoside-based drugs were collected from literature to assess their effectiveness against KRAS G12C. The study incorporates in-silico molecular simulations and molecular docking examinations of these nucleoside-derived drugs with the KRAS G12C protein using Protein Data Bank (PDB) ID: 5V71. The docking outcomes indicated that two drugs, Azacitidine and Ribavirin, exhibited substantial binding affinities of -8.7 and -8.3 kcal/mol, respectively. These drugs demonstrated stability in binding to the active site of the protein during simulation studies. Root mean square deviation (RMSD) analyses indicated that the complexes closely adhered to an equilibrium RMSD value ranging from 0.17 to 0.2 nm. Additionally, % occupancies, bond angles and the length of hydrogen bonds were calculated. These findings suggest that Azacitidine and Ribavirin may potentially serve as candidates for repurposing in individuals with KRAS-dependent cancers.Communicated by Ramaswamy H. Sarma.

The emerging role of noncoding RNAs in the EGFR signaling pathway in lung cancer.

Noncoding ribonucleic acids (ncRNAs) have surfaced as essential orchestrators within the intricate system of neoplastic biology. Specifically, the epidermal growth factor receptor (EGFR) signalling cascade shows a central role in the etiological underpinnings of pulmonary carcinoma. Pulmonary malignancy persists as a preeminent contributor to worldwide mortality attributable to malignant neoplasms, with non-small cell lung carcinoma (NSCLC) emerging as the most predominant histopathological subcategory. EGFR is a key driver of NSCLC, and its dysregulation is frequently associated with tumorigenesis, metastasis, and resistance to therapy. Over the past decade, researchers have unveiled a complex network of ncRNAs, encompassing microRNAs, long noncoding RNAs, and circular RNAs, which intricately regulate EGFR signalling. MicroRNAs, as versatile post-transcriptional regulators, have been shown to target various components of the EGFR pathway, influencing cancer cell proliferation, migration, and apoptosis. Additionally, ncRNAs have emerged as critical modulators of EGFR signalling, with their potential to act as scaffolds, decoys, or guides for EGFR-related proteins. Circular RNAs, a relatively recent addition to the ncRNA family, have also been implicated in EGFR signalling regulation. The clinical implications of ncRNAs in EGFR-driven lung cancer are substantial. These molecules exhibit diagnostic potential as robust biomarkers for early cancer detection and personalized treatment. Furthermore, their predictive value extends to predicting disease progression and therapeutic outcomes. Targeting ncRNAs in the EGFR pathway represents a novel therapeutic approach with promising results in preclinical and early clinical studies. This review explores the increasing evidence supporting the significant role of ncRNAs in modulating EGFR signalling in lung cancer, shedding light on their potential diagnostic, prognostic, and therapeutic implications.

From inflammation to metastasis: The central role of miR-155 in modulating NF-κB in cancer.

Cancer is a multifaceted, complex disease characterized by unchecked cell growth, genetic mutations, and dysregulated signalling pathways. These factors eventually cause evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, which makes it difficult for targeted therapeutic interventions to be effective. MicroRNAs (miRNAs) are essential gene expression regulators linked to several biological processes, including cancer and inflammation. The NF-κB signalling pathway, a critical regulator of inflammatory reactions and oncogenesis, has identified miR-155 as a significant participant in its modulation. An intricate network of transcription factors known as the NF-κB pathway regulates the expression of genes related to inflammation, cell survival, and immunological responses. The NF-κB pathway's dysregulation contributes to many cancer types' development, progression, and therapeutic resistance. In numerous cancer models, the well-studied miRNA miR-155 has been identified as a crucial regulator of NF-κB signalling. The p65 subunit and regulatory molecules like IκB are among the primary targets that miR-155 directly targets to alter NF-κB activity. The molecular processes by which miR-155 affects the NF-κB pathway are discussed in this paper. It also emphasizes the miR-155's direct and indirect interactions with important NF-κB cascade elements to control the expression of NF-κB subunits. We also investigate how miR-155 affects NF-κB downstream effectors in cancer, including inflammatory cytokines and anti-apoptotic proteins.

Identification of IL-2 inducible tyrosine kinase inhibitors by quantum mechanics and ligand based virtual screening approaches.

Interleukin-2-inducible T-cell kinase (ITK) is a crucial intracellular signaling mediator in normal and malignant T-cells and natural killer cells. Selective inhibition of ITK might be useful for treating a variety of disorders including; autoimmune, inflammatory, and neoplastic disorders. Over the past two decades, the clinical management of ITK inhibitors has progressed dramatically. So far, specific inhibitor with no off-target effects against ITK is available. Herein, we aim to discover potential virtual hits to fasten the process of drug design and development against ITK. In this regard, the key chemical characteristics of ITK inhibitors were identified using ligand-based pharmacophore modeling. The validated pharmacophore comprises one hydrogen bond donor and three hydrogen bond acceptors and was utilized as a 3D query in virtual screening using ZINC, Covalent, and in-house databases. A total of 12 hit compounds were chosen on the basis of their critical interactions with the significant amino acids of ITK. The orbital energies such as HOMO and LUMO of the hit compounds were calculated to evaluate the inhibitor's potencies. Further, molecular dynamics simulation demonstrated the stability of ITK upon binding of selected virtual hits. Binding energy using the MMGBSA method showed the potential binding affinity of all the hits with ITK. The research identifies key chemical characteristics with geometric restrictions that lead to ITK inhibition.Communicated by Ramaswamy H. Sarma.

Unveiling the potential of proteomic and genetic signatures for precision therapeutics in lung cancer management.

Lung cancer's enduring global significance necessitates ongoing advancements in diagnostics and therapeutics. Recent spotlight on proteomic and genetic biomarker research offers a promising avenue for understanding lung cancer biology and guiding treatments. This review elucidates genetic and proteomic lung cancer biomarker progress and their treatment implications. Technological strides in mass spectrometry-based proteomics and next-generation sequencing enable pinpointing of genetic abnormalities and abnormal protein expressions, furnishing vital data for precise diagnosis, patient classification, and customized treatments. Biomarker-driven personalized medicine yields substantial treatment improvements, elevating survival rates and minimizing adverse effects. Integrating omics data (genomics, proteomics, etc.) enhances understanding of lung cancer's intricate biological milieu, identifying novel treatment targets and biomarkers, fostering precision medicine. Liquid biopsies, non-invasive tools for real-time treatment monitoring and early resistance detection, gain popularity, promising enhanced management and personalized therapy. Despite advancements, biomarker repeatability and validation challenges persist, necessitating interdisciplinary efforts and large-scale clinical trials. Integrating artificial intelligence and machine learning aids analyzing vast omics datasets and predicting treatment responses. Single-cell omics reveal cellular connections and intratumoral heterogeneity, valuable for combination treatments. Biomarkers enable accurate diagnosis, tailored medicines, and treatment response tracking, significantly impacting personalized lung cancer care. This approach spurs patient-centered trials, empowering active patient engagement. Lung cancer proteomic and genetic biomarkers illuminate disease biology and treatment prospects. Progressing towards individualized efficient therapies is imminent, alleviating lung cancer's burden through ongoing research, omics integration, and technological strides.

Bioactive substances of cyanobacteria and microalgae: Sources, metabolism, and anticancer mechanism insights.

Cyanobacteria and microalgae contain various phytochemicals, including bioactive components in the form of secondary metabolites, namely flavonoids, phenolic acids, terpenoids, and tannins, with remarkable anticancer effects. This review highlights the recent advances in bioactive compounds, with potential anticancer activity, produced by cyanobacteria and microalgae. Previous in vitro investigations showed that many of these bioactive compounds exhibit potent effects against different human cancer types, such as leukemia and breast cancers. Multiple mechanisms implicated in the antitumor effect of these compounds were elucidated, including their ability to target cellular, subcellular, and molecular checkpoints linked to cancer development and promotion. Recent findings have highlighted various mechanisms of action of bioactive compounds produced by cyanobacteria and microalgae, including induction of autophagy and apoptosis, inhibition of telomerase and protein kinases, as well as modulation of epigenetic modifications. In vivo investigations have demonstrated a potent anti-angiogenesis effect on solid tumors, as well as a reduction in tumor volume. Some of these compounds were examined in clinical investigations for certain types of cancers, making them potent candidates/scaffolds for antitumor drug development.