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.

Curcumin nanogel and its efficacy against oxidative stress and inflammation in rat models of ischemic stroke.

Aim: The study was designed to develop and analyze curcumin nanoparticles. Methods: Curcumin nanoparticles were formulated and evaluated. Their efficacy in protecting against brain damage was investigated in a rat model of ischemic stroke, considering motor function, muscle strength and antioxidant enzyme activity. Results: Curcumin nanoparticles displayed a zeta potential of -55 ± 13.5 mV and an average particle size of 51.40 ± 21.70 nm. In ischemic stroke rat models, curcumin nanoparticle treatment significantly improved motor functions, and muscle strength and increased the activities of antioxidant enzymes like glutathione peroxidase, glutathione, glutathione S-transferase, superoxide dismutase and catalase, reducing oxidative stress and inflammation. Conclusion: Curcumin nanoparticles showed significant neuroprotective effects in ischemic stroke models.

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Targeting PD-1/PD-L-1 immune checkpoint inhibition for cancer immunotherapy: success and challenges.

The programmed death-1 receptor (PD-1) acts as a T-cell brake, and its interaction with ligand-1 (PD-L-1) interferes with signal transduction of the T-cell receptor. This leads to suppression of T-cell survival, proliferation, and activity in the tumor microenvironment resulting in compromised anticancer immunity. PD-1/PD-L-1 interaction blockade shown remarkable clinical success in various cancer immunotherapies. To date, most PD-1/PD-L-1 blockers approved for clinical use are monoclonal antibodies (mAbs); however, their therapeutic use are limited owing to poor clinical responses in a proportion of patients. mAbs also displayed low tumor penetration, steep production costs, and incidences of immune-related side effects. This strongly indicates the importance of developing novel inhibitors as cancer immunotherapeutic agents. Recently, advancements in the small molecule-based inhibitors (SMIs) that directly block the PD-1/PD-L-1 axis gained attention from the scientific community involved in cancer research. SMIs demonstrated certain advantages over mAbs, including longer half-lives, low cost, greater cell penetration, and possibility of oral administration. Currently, several SMIs are in development pipeline as potential therapeutics for cancer immunotherapy. To develop new SMIs, a wide range of structural scaffolds have been explored with excellent outcomes; biphenyl-based scaffolds are most studied. In this review, we analyzed the development of mAbs and SMIs targeting PD-1/PD-L-1 axis for cancer treatment. Altogether, the present review delves into the problems related to mAbs use and a detailed discussion on the development and current status of SMIs. This article may provide a comprehensive guide to medicinal chemists regarding the potential structural scaffolds required for PD-1/PD-L-1 interaction inhibition.

A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality.

The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.

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.

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.

Daidzein from Dietary Supplement to a Drug Candidate: An Evaluation of Potential.

Daidzein (DDZ) is a well-known nutraceutical supplement belonging to the class of isoflavones. It is isolated from various sources such as alfalfa, soybean, and red clover. It demonstrates a broad array of pharmacological/beneficial properties such as cardiovascular exercise, cholesterol reduction, and anticancer, antifibrotic, and antidiabetic effects, which make it effective in treating a wide range of diseases. Its structure and operation are the same as those of human estrogens, which are important in preventing osteoporosis, cancer, and postmenopausal diseases. It is thus a promising candidate for development as a phytopharmaceutical. Addressing safety, efficacy, and physicochemical properties are the primary prerequisites. DDZ is already ingested every day in varying amounts, so there should not be a significant safety risk; however, each indication requires a different dose to be determined. Some clinical trials are already being conducted globally to confirm its safety, efficacy, and therapeutic potential. Furthermore, as a result of its therapeutic influence on health, in order to establish intellectual property, patents are utilized. In light of the vast potential of eugenol, this review presents a detailed data collection on DDZ to substantiate the claim to develop it in the therapeutic category.

Exploring EGFR inhibitors with the aid of virtual screening, docking, and dynamics simulation studies.

In humans, Epidermal Growth Factor Receptor (EGFR) is linked to small-cell lung cancer, breast cancer, and glioblastoma. Receptor kinase inhibitors against EGFR have become a standard treatment option for non-small cell lung cancer (NSCLC), breast cancer patients, and even for those with EGFR mutations or resistance. About 2734 FDA-approved medication compounds were subjected to virtual screening for EGFR kinase inhibitory activity. The top 30 molecules were chosen based on the binding affinity scores and subjected to extra-precision docking and binding free energy analysis. The ADMET profile of the top three hit molecules was verified to confirm their druggability nature. Top three hits- compound 1047 (ZINC000001550477), 1302 (ZINC00003781952), and 2332 (ZINC000019632618) were identified on account of their MMGBSA binding affinity values. The top three hit compounds were subjected to molecular dynamics (MD) simulation for 100 ns. The dynamic nature of the ligand-protein complex was analyzed which corroborated the results of molecular docking and MMGBSA analysis studies. All the top three hits were further subjected to steered MD studies for testing the strength of these ligand-receptor binding in the presence of an external force. Compound 2332 (ZINC000019632618) was identified as the best hit molecule that can be used as a lead to develop newer derivatives of EGFR kinase inhibitors.Communicated by Ramaswamy H. Sarma.

Structural Complementarity of Bruton's Tyrosine Kinase and Its Inhibitors for Implication in B-Cell Malignancies and Autoimmune Diseases.

Bruton's tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is also expressed in haematogenic and innate immune cells. Inhibition of BTK hyperactivity is implicated in B-cell malignancies and autoimmune diseases. This review derives the structural complementarity of the BTK-kinase domain and its inhibitors from recent three-dimensional structures of inhibitor-bound BTK in the protein data bank (PDB). Additionally, this review analyzes BTK-mediated effector responses of B-cell development and antibody production. Covalent inhibitors contain an α, ß-unsaturated carbonyl moiety that forms a covalent bond with Cys481, stabilizing αC-helix in inactive-out conformation which inhibits Tyr551 autophosphorylation. Asn484, located two carbons far from Cys481, influences the stability of the BTK-transition complex. Non-covalent inhibitors engage the BTK-kinase domain through an induced-fit mechanism independent of Cys481 interaction and bind to Tyr551 in the activation kink resulting in H3 cleft, determining BTK selectivity. Covalent and non-covalent binding to the kinase domain of BTK shall induce conformational changes in other domains; therefore, investigating the whole-length BTK conformation is necessary to comprehend BTK's autophosphorylation inhibition. Knowledge about the structural complementarity of BTK and its inhibitors supports the optimization of existing drugs and the discovery of drugs for implication in B-cell malignancies and autoimmune diseases.

Exploring the multifocal role of phytoconstituents as antidepressants.

Depression is the most prevalent and devastating neuropsychiatric disorder. There are several conventional antidepressants used for the treatment of depression. But due to their undesired adverse effects, patient compliance is very poor. Thus, developing novel medications for the treatment of depression is a critical strategic priority for meeting therapeutic demands. Current research is looking for alternatives to traditional antidepressants to reduce undesired side effects and increase efficacy. Phytoconstituents provide a wide research range in antidepressant treatments. In the present article, we have conducted a comprehensive assessment of neurological evidence, which supports the usefulness of phytoconstituents in the treatment of the depressive disorder. Secondary plant metabolites including alkaloids, polyphenols, glycosides, saponins, and terpenoids were found to exhibit antidepressant action. Most of the phytoconstituents were found to mediate their antidepressant effect through the upregulation of brain-derived neurotrophic factor (BDNF), serotonin, noradrenaline, and dopamine. Some were also found to exert antidepressant effects by inhibiting the monoamine oxidase (MAO) activity and hypothalamic-pituitary-adrenal (HPA) axis overactivity.

Effect of Drying Temperature on Physical, Chemical, and Antioxidant Properties of Ginger Oil Loaded Gelatin-Sodium Alginate Edible Films.

The drying temperature is one of the crucial parameters that impacts the physical, chemical, and biological properties of edible films (EFs). This parameter determines the degree of crystallinity, which can further impact the film's mechanical, barrier, and optical properties. The present work is designed to investigate the effect of different drying temperature conditions (25 °C and 45 °C) on ginger essential oil (GEO) loaded Gelatin-sodium alginate composite films over their physical, chemical, and antioxidant properties. Results indicated that drying of films at 25 °C had a positive effect on certain properties of the EFs, such as the moisture content (MC), water solubility (S), swelling degree (SD), water vapor permeability (WVP), and mechanical and optical properties. SEM analysis showed that films dried at 25 °C presented more uniform surface properties with fewer cracks and pores compared to films dried at 45 °C. TGA analysis demonstrated the higher thermal stability of the films when dried at 25 °C. Findings obtained from X-ray diffraction (XRD) and fourier-transform infrared spectroscopy (FTIR) showed film crystallinity and electrostatic interactions between GE, SA, and GEO. Results obtained from antioxidant assays revealed that films dried at 25 °C showed comparable antioxidant capacity to that of butylated hydroxytoluene (BHT). Furthermore, it was found that the addition of SA and GEO to the blank GE films improved their physical, chemical, and antioxidant properties. The present work suggests that GEO loaded GE-SA based films showed better physical, chemical, and antioxidant potential when dried at a lower temperature. These novel materials can be utilized as potential packaging materials in the food industry.

Mitochondrial targeting theranostic nanomedicine and molecular biomarkers for efficient cancer diagnosis and therapy.

Mitochondria play a crucial part in the cell's ability to adapt to the changing microenvironments and their dysfunction is associated with an extensive array of illnesses, including cancer. Mitochondrial dysfunction has been identified as a potential therapeutic target for cancer therapy. The objective of this article is to give an in-depth analysis of cancer treatment that targets the mitochondrial genome at the molecular level. Recent studies provide insights into nanomedicine techniques and theranostic nanomedicine for mitochondrial targeting. It also provides conceptual information on mitochondrial biomarkers for cancer treatment. Major drawbacks and challenges involved in mitochondrial targeting for advanced cancer therapy have also been discussed. There is a lot of evidence and reason to support using nanomedicine to focus on mitochondrial function. The development of a delivery system with increased selectivity and effectiveness is a prerequisite for a theranostic approach to cancer treatment. If given in large amounts, several new cancer-fighting medicines have been created that are toxic to healthy cells as well. For effective therapy, a new drug must be developed rather than an old one. When it comes to mitochondrial targeting therapy, theranostic techniques offer valuable insight.

The therapeutic role of nutraceuticals targeting the Nrf2/HO-1 signaling pathway in liver cancer.

Liver cancer (L.C.) is the most common cause of cancer death in the United States and the fifth most common globally. The overexpression of nuclear factor E2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) caused by oxidative stress has been associated with tumor growth, aggressiveness, treatment resistance, and poor prognosis. Nutraceuticals that inhibit Nrf2/HO-1 signaling may become the most effective strategy to treat liver cancer. Phytochemicals found in fruits and vegetables, also known as nutraceuticals, tend to emerge as chemopreventive agents, with the added benefit of low toxicity and high nutritional values. This paper reviews the present scientific knowledge of the Nrf2/HO-1 signaling as a possible target molecule for chemotherapeutic agents, its basic control mechanisms, and Nrf2/HO-1 inducers produced from natural products that might be employed as cancer chemopreventive drugs. The growing interest in the contribution of the Nrf2/ARE/HO-1 signaling in the development of liver cancer and the Use of nutraceuticals to treat liver cancer by targeting Nrf2/ARE/HO-1. PRACTICAL APPLICATIONS: An increase in Nrf2 expression indicates that Nrf2 is the most important player in liver cancer. Cancer patients are more resistant to chemotherapy because of this erroneous Nrf2 signaling. Furthermore, an increasing body of evidence indicates that activation of the Nrf2/HO-1 pathway results in the production of phase II detoxifying and antioxidant enzymes, which serve a defense purpose in cells. As a consequence, treating liver cancer. This master regulator may be a possibility. Nutraceuticals that reduce Nrf2/HO-1 signaling may be the most effective strategy for preventing liver cancer. The methods of action of numerous natural substances are examined in this article.

Expatiating the Pharmacological and Nanotechnological Aspects of the Alkaloidal Drug Berberine: Current and Future Trends.

Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer's disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.

Sulforaphane: A review of its therapeutic potentials, advances in its nanodelivery, recent patents, and clinical trials.

Traditionally, herbal supplements have shown an exceptional potential of desirability for the prevention of diseases and their treatment. Sulforaphane (SFN), an organosulfur compound belongs to the isothiocyanate (ITC) group and is mainly found naturally in cruciferous vegetables. Several studies have now revealed that SFN possesses broad spectrum of activities and has shown extraordinary potential as antioxidant, antitumor, anti-angiogenic, and anti-inflammatory agent. In addition, SFN is proven to be less toxic, non-oxidizable, and its administration to individuals is well tolerated, making it an effective natural dietary supplement for clinical trials. SFN has shown its ability to be a promising future drug molecule for the management of various diseases mainly due to its potent antioxidant properties. In recent times, several newer drug delivery systems were designed and developed for this potential molecule in order to enhance its bioavailability, stability, and to reduce its side effects. This review focuses to cover numerous data supporting the wide range of pharmacological activities of SFN, its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials on SFN are also summarized.

Spectroscopic characterization of the interactions of bovine serum albumin with medicinally important metal ions: platinum (IV), iridium (III) and iron (II).

Serum albumin protein plays a key role in the transportation and distribution of bioactive species including metal ions and metal-based drugs and, therefore, the nature of their binding could provide important insight for the development of new drugs. In the present investigation, binding interactions of bovine serum albumin (BSA) with three biologically important metal ions: Pt4+, Ir3+ and Fe2+ were screened using easy-to-use and cost-effective Fourier-Transform Infrared (FT-IR) and Ultraviolet-Visible (UV-Vis) spectroscopic techniques. Prior to the screening, the protein and metal ions were allowed to interact at physiological pH (7.4) and the spectral changes were monitored upon interaction. In FT-IR spectrum, the position of amide I band (C=O stretching) was shifted from 1652 cm-1 in case of free BSA to 1659, 1657 and 1656 cm-1 in BSA-Pt4+, BSA-Ir3+ and BSA-Fe2+ complexes, respectively. This spectral shifting was due to the binding of metal ions to N and O atoms of BSA peptide bonds. The interaction was further demonstrated by a remarkable reduction in spectral intensities of amide I and II bands. Secondary protein structure analysis revealed conformational changes characterized by a substantial decrease in α-helix (11.29-27.41%) accompanied by an increase in ß-sheet and ß-antiparallel contents. The absorption of BSA at a constant concentration at 280 nm was successively reduced as the concentration of Pt4+ and Ir3+ ions increased. On the other hand, the absorption of BSA-Fe2+ complex successively increased with the increase in the concentration of Fe2+ in the test solution. The binding constants for BSA-Pt4+, BSA-Ir3+ and BSA-Fe2+ complexes were calculated to be 1.55×104, 5.67×104 and 3.78×104 M-1, respectively. The results revealed that the three metal ions showed binding affinities with the BSA protein in the order: Ir3+>Fe2+>Pt4+.

Exploring the Molecular Mechanisms of 17ß-HSD5-induced Carcinogenicity of Catha edulis via Molecular Modeling Approach.

BACKGROUND: The tradition of khat chewing has been deep-rooted in the African and Arabian Peninsula for centuries. Due to its amphetamine-like psycho-stimulant or euphoric effect, khat has been used by millions in Somalia, Ethiopia, Saudi Arabia and Yemen. The long-term use of khat can induce many major health outcomes, which may be serious and irreversible. OBJECTIVE: Prolonged use of khat constituents has been associated with different types of cancers such as prostatic, breast and ovarian cancer. However, it has been very difficult to identify the molecular targets involved in khat carcinogenesis that interact with the Khat constituents by in vitro/in vivo experimental tools. METHODS: In silico tools were used to predict potential targets involved in the carcinogenesis of khat. Pass on-line prediction server was used for the prediction of a potential molecular target for khat constituents. Molecular Dynamics simulation and MM-GBSA calculation of the predicted target were carried out. RESULTS: Molecular Dynamics simulation and MM-GBSA calculation revealed that among khat constituents, ß-sitosterol showed a high binding affinity towards 17ß-HSD5. On the other hand, this study highlights for the first time some new interactions, which were observed in the case of cathine, cathinone and nerol during the simulation. CONCLUSION: In silico molecular dynamic simulation tools were used for the first time to investigate the molecular mechanism of widely used leaves of psychoactive khat (Catha edulis) constituent. The present study provides deep insight to understand the effect of khat constituents involved in the impairment of the reproductive system and its binding to 17ß-HSD5. ADMET profiling also suggested that few khat constituents do not fulfill the requirements of the Lipinski rule of five i.e. poor absorption and blood-brain barrier impermeability.

Bioactive Natural Antivirals: An Updated Review of the Available Plants and Isolated Molecules.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.