Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics.

Diabetes mellitus is a chronic hormonal and metabolic disorder in which our body cannot generate necessary insulin or does not act in response to it, accordingly, ensuing in discordantly high blood sugar (glucose) levels. Diabetes mellitus can lead to systemic dysfunction in the multiorgan system, including cardiac dysfunction, severe kidney disease, lowered quality of life, and increased mortality risk from diabetic complications. To uncover possible therapeutic targets to treat diabetes mellitus, the in silico drug design technique is widely used, which connects the ligand molecules with target proteins to construct a protein-ligand network. To identify new therapeutic targets for type 2 diabetes mellitus, Azadirachta indica is subjected to phytochemical screening using in silico molecular docking, pharmacokinetic behavior analysis, and simulation-based molecular dynamic analysis. This study has analyzed around 63 phytochemical compounds, and the initial selection of the compounds was made by analyzing their pharmacokinetic properties by comparing them with Lipinskis rule of 5. The selected compounds were subjected to molecular docking. The top four ligand compounds were reported along with the control drug nateglinide based on their highest negative molecular binding affinity. The protein-ligand interaction of selected compounds has been analyzed to understand better how compounds interact with the targeted protein structure. The results of the in silico analysis revealed that 7-Deacetyl-7-oxogedunin had the highest negative docking score of 8.9Kcal/mol and also demonstrated standard stability in a 100ns molecular dynamic simulation performed with insulin receptor ectodomain. It has been found that these substances may rank among the essential supplementary antidiabetic drugs for treating type 2 diabetes mellitus. It is suggested that more in vivo and in vitro research studies be carried out to support the conclusions drawn from this in silico research strategy.

Nanotechnology encompasses a wide range of devices derived from biology, engineering, chemistry, and physics, and this scientific field is composed of great collaboration among researchers from several fields. It has diverse implications notably smart sensing technologies, effective disease diagnosis, and sometimes used in treatment. In medical science, the implications of nanotechnology include the development of elements and devices that interact with the body at subcellular (i.e., molecular) levels exhibiting high sensitivity and specificity. There is a plethora of new chances for medical science and disease treatment to be discovered and exploited in the rapidly developing field of nanotechnology. In different sectors, nanomaterials are used just because of their special characteristics. Their large surface area of them enables higher reactivity with greater efficiency. Furthermore, special surface chemistry is displayed by nanomaterials which compare to conventional materials and facilitate the nanomaterials to decrease pollutants efficiently. Recently, nanomaterials are used in some countries to reduce the levels of contaminants in water, air, and soil. Moreover, nanomaterials are used in the cosmetics and medical industry, and it develops the drug discovery (DD) system. Among a huge number of nanomaterials, Cu, Ag, TiO₂, ZnO, Fe₃O₄, and carbon nanotubes (CNTs) are extensively used in different industries for various purposes. This extensive review study has introduced the major scientific and technical features of nanotechnology, as well as some possible clinical applications and positive feedback in environmental waste management and drug delivery systems.

Dengue is a Flavivirus infection transmitted through mosquitoes of the Aedes genus, which is known to occur in over 100 countries of the world. Dengue has no available drugs for treatment; CYD-TDV is the only vaccine thus far approved for use by a few countries in the world. In the absence of drugs and a widely approved vaccine, attention has been focused on plant-derived compounds to the discovery of a potential therapeutic for DENV. The present study aimed to determine, in silico, the binding energies of the steroidal saponins, melongosides, to NS2B-NS3 activator protease of DENV-2, which plays an essential role in the viral replication. The blind molecular docking studies carried out gave binding energies (ΔG=kcal/mol) of melongosides B, F, G, H, N, O, and P as 7.7, 8.2, 7.6, 7.8, 8.3, 8.0, and 8.0, respectively. All the melongosides interacted with the NS3 protease part of NS2B-NS3. Melongosides B, F, and N showed interactions with His51, while melongoside G interacted with Asp75 of NS3, to be noted, these are important amino acid residues in the catalytic site of the NS3 protease. However, the 200ns molecular dynamic simulation experiment indicates significant stability of the protein-ligand interactions with the RMSD values of 2.5Å, thus suggesting a better docking position and no disruption of the protein-ligand structure. Taken together, melongosides need further attention for more scientific studies as a DENV inhibitory agent, which if proven, in vivo and in clinical trials, can be a useful therapeutic agent against at least DENV-2.

Breast and lung cancer are two of the most lethal forms of cancer, responsible for a disproportionately high number of deaths worldwide. Both doctors and cancer patients express alarm about the rising incidence of the disease globally. Although targeted treatment has achieved enormous advancements, it is not without its drawbacks. Numerous medicines and chemotherapeutic drugs have been authorized by the FDA; nevertheless, they can be quite costly and often fall short of completely curing the condition. Therefore, this investigation has been conducted to identify a potential medication against breast and lung cancer through structural modification of genistein. Genistein is the active compound in Glycyrrhiza glabra (licorice), and it exhibits solid anticancer efficiency against various cancers, including breast cancer, lung cancer, and brain cancer. Hence, the design of its analogs with the interchange of five functional groups—COOH, NH₂ and OCH₃, Benzene, and NH-CH₂-CH₂-OH—have been employed to enhance affinities compared to primary genistein. Additionally, advanced computational studies such as PASS prediction, molecular docking, ADMET, and molecular dynamics simulation were conducted. Firstly, the PASS prediction spectrum was analyzed, revealing that the designed genistein analogs exhibit improved antineoplastic activity. In the prediction data, breast and lung cancer were selected as primary targets. Subsequently, other computational investigations were gradually conducted. The mentioned compounds have shown acceptable results for in silico ADME, AMES toxicity, and hepatotoxicity estimations, which are fundamental for their oral medication. It is noteworthy that the initial binding affinity was only −8.7 kcal/mol against the breast cancer targeted protein (PDB ID: 3HB5). However, after the modification of the functional group, when calculating the binding affinities, it becomes apparent that the binding affinities increase gradually, reaching a maximum of −11.0 and −10.0 kcal/mol. Similarly, the initial binding affinity was only −8.0 kcal/mol against lung cancer (PDB ID: 2P85), but after the addition of binding affinity, it reached −9.5 kcal/mol. Finally, a molecular dynamics simulation was conducted to study the molecular models over 100 ns and examine the stability of the docked complexes. The results indicate that the selected complexes remain highly stable throughout the 100-ns molecular dynamics simulation runs, displaying strong correlations with the binding of targeted ligands within the active site of the selected protein. It is important to further investigate and proceed to clinical or wet lab experiments to determine the practical value of the proposed compounds.