In silico analysis of Diosmetin as an effective chemopreventive agent against prostate cancer: molecular docking, validation, dynamic simulation and pharmacokinetic prediction-based studies.

Prostate cancer is the second most dangerous cancer type worldwide. While various treatment options are present i.e. agonists and antagonists, their utilization leads to adverse effects and due to this resistance developing, ultimately the outcome is remission. So, to overcome this issue, we have undertaken an in-silico investigation to identify promising and unique flavonoid candidates for combating prostate cancer. Using GOLD software, the study assessed the effectiveness of 560 natural secondary polyphenols against CDKN2. Protein Data Bank was used to retrieve the 3D crystal structure of CDKN2 (PDB Id: 4EK3) and we retrieved the structure of selected secondary polyphenols from the PubChem database. The compound Diosmetin shows the highest GOLD score with the selected Protein i.e. CDKN2 which is 58.72. To better understand the 2-dimensional and 3-dimensional interactions, the interacting amino acid residues were visualised using Discovery Studio 3.5 and Maestro 13.5. Using Schrodinger-Glide, the Diosmetin and CDKN2 were re-docked, and decoy ligands were docked to CDKN2, which was used to further ascertain the study. The ligands with the highest Gold score were forecasted for pharmacokinetics characteristics, and the results were tabulated and analysed. Utilising the Gromacs software and Desmond packages, 100 ns of Diosmetin molecular dynamics simulations were run to evaluate the structural persistence and variations of protein-ligand complexes. Additionally, our investigation revealed that Diosmetin had a better binding affinity with CDKN2 measuring 58.72, and it also showed remarkable stability across a 100-ns simulation. Thus, following in-vitro and in-vivo clinical studies, diosmetin might lead to the Prostate regimen.Communicated by Ramaswamy H. Sarma.

Lipid-based nanoparticles for treatment of cancer.

Investigators were continuously creating novel nanotechnologies to address unmet requirements throughout the administration of therapeutic medicines & imaging agents for cancer treatment & diagnostics, appropriately. LNPs(Lipid nanoparticles) are legitimate particulates (approx. 100 nm in size) gathered from various lipid as well as other biochemical compounds which overall functionality to resolve biological barriers (biobarriers), allowing LNPs to selectively collect somewhere outside of disease-target cells again for responsive therapeutics. Most pharmaceutically important compounds were insoluble throughout water solutions, were chemical & physiologically unstable, or have toxicities. Among the most potential drug carrier for bioactive organic compounds is LBNPs (Lipid based nanoparticles) technologies. Its present use in chemotherapy have transformed treatment for cancer by increasing the antitumor effect of a number of chemotherapeutics. Because they may be created using naturally occurring sources, LBNPs have great temporal and thermal stability, maximum load potential, simplicity of preparations, cheap manufacturing costs, & big manufacturing output. Furthermore, combining chemotherapeutic drugs with LNPs reduces active therapeutic dosage and toxicities, lowers treatment resistance, & raises drug concentration in tumour cells while reducing concentrations in normal tissue. LBNPs were widely studied in cancer treatment, both in vitro and in vivo, with encouraging outcomes in certain clinical trials. This study provides an overview of the many types of LBNPs which have been created in latest years and their applications and contributions in different types of cancers.

Immune Regulation of Skin Wound Healing: Mechanisms and Novel Therapeutic Targets.

Significance: The immune system plays a central role in orchestrating the tissue healing process. Hence, controlling the immune system to promote tissue repair and regeneration is an attractive approach when designing regenerative strategies. This review discusses the pathophysiology of both acute and chronic wounds and possible strategies to control the immune system to accelerate chronic wound closure and promote skin regeneration (scar-less healing) of acute wounds. Recent Advances: Recent studies have revealed the key roles of various immune cells and immune mediators in skin repair. Thus, immune components have been targeted to promote chronic wound repair or skin regeneration and several growth factors, cytokines, and biomaterials have shown promising results in animal models. However, these novel strategies are often struggling to meet efficacy standards in clinical trials, partly due to inadequate drug delivery systems and safety concerns. Critical Issues: Excess inflammation is a major culprit in the dysregulation of normal wound healing, and further limiting inflammation effectively reduces scarring. However, current knowledge is insufficient to efficiently control inflammation and specific immune cells. This is further complicated by inadequate drug delivery methods. Future Directions: Improving our understanding of the molecular pathways through which the immune system controls the wound healing process could facilitate the design of novel regenerative therapies. Additionally, better delivery systems may make current and future therapies more effective. To promote the entry of current regenerative strategies into clinical trials, more evidence on their safety, efficacy, and cost-effectiveness is also needed.

An update on application of nanotechnology and stem cells in spinal cord injury regeneration.

Spinal cord injury (SCI) is damage to the spinal cord that leads to sudden loss of motor and autonomic function and sensory under the level of the injury. The pathophysiological advancement of SCI is divided into two categories: primary injury and secondary injury. Due to the loss of motor, sensory, or cognitive function, a patient's quality of life is likely reduced and places a great burden on society in order to supply health care costs. Therefore, it is important to develop suitable therapeutic strategies for SCI therapy. Nano biomedical systems and stem cell based therapy have the potential to provide new therapeutic availability and efficacy over conventional medicine. Due to their unique properties, nanomaterials and mesenchymal stem cells can be used to offer efficient treatments. Nanoparticles have a potential to deliver therapeutic molecules to the target tissue of interest, reducing side effects of untargeted therapies in unwanted areas. Mesenchymal stem cells (MSCs) can reduce activating inflammation responses that lead to cell death and promote functional recovery and cell growth. We review recent uses of nanomaterials and stem cells in regeneration of SCI.