Identification of novel scaffolds targeting SIRT3 through molecular modeling techniques for the treatment of Hepatocellular carcinoma.

Hepatocellular carcinoma is one of the top causes of cancer-related death globally. SIRT3 belongs to the Sirtuin family of proteins, a collection of NAD+-dependent enzymes that play a role in controlling several cellular functions, including metabolism, aging, and stress response. SIRT3 expression has been discovered to be often downregulated in HCC tissues relative to normal liver tissues. Hence, SIRT3 may function as a tumor suppressor in HCC. In the present study, pharmacophore-based virtual screening of a small molecule database was performed initially, and then the screened hits were docked to the active site of SIRT3 to choose the best binding modes. One co-crystal ligand (PDB name: 1NQ) was utilized as a template to generate pharmacophore model query. A total of 0.2 million compounds from the VITAS-M Lab database were downloaded and prepared for virtual screening. Following database preparation, ligand-based virtual screening was performed using the pharmacophore query model generated in the previous phase. The compounds with the same pharmacophoric characteristics as the query at the same distance were screened. There were a total of 74 hits that matched the query model. These compounds were then docked to the SIRT3 using the standard precision protocol of the glide tool. To select hits with high binding affinities, a threshold of -8 kcal/mol was used. Based on the glide gscore, two hits were chosen. These two hits were selected to investigate the stability of the protein-ligand complex by molecular dynamics simulation. All of these findings indicate that the selected hit compounds C1 and C2 can serve as lead compounds in inhibiting the biological activity of SIRT3 requiring further detailed investigations.Communicated by Ramaswamy H. Sarma.

Artificial intelligence in cancer diagnosis and therapy: Current status and future perspective.

Artificial intelligence (AI) in healthcare plays a pivotal role in combating many fatal diseases, such as skin, breast, and lung cancer. AI is an advanced form of technology that uses mathematical-based algorithmic principles similar to those of the human mind for cognizing complex challenges of the healthcare unit. Cancer is a lethal disease with many etiologies, including numerous genetic and epigenetic mutations. Cancer being a multifactorial disease is difficult to be diagnosed at an early stage. Therefore, genetic variations and other leading factors could be identified in due time through AI and machine learning (ML). AI is the synergetic approach for mining the drug targets, their mechanism of action, and drug-organism interaction from massive raw data. This synergetic approach is also facing several challenges in data mining but computational algorithms from different scientific communities for multi-target drug discovery are highly helpful to overcome the bottlenecks in AI for drug-target discovery. AI and ML could be the epicenter in the medical world for the diagnosis, treatment, and evaluation of almost any disease in the near future. In this comprehensive review, we explore the immense potential of AI and ML when integrated with the biological sciences, specifically in the context of cancer research. Our goal is to illuminate the many ways in which AI and ML are being applied to the study of cancer, from diagnosis to individualized treatment. We highlight the prospective role of AI in supporting oncologists and other medical professionals in making informed decisions and improving patient outcomes by examining the intersection of AI and cancer control. Although AI-based medical therapies show great potential, many challenges must be overcome before they can be implemented in clinical practice. We critically assess the current hurdles and provide insights into the future directions of AI-driven approaches, aiming to pave the way for enhanced cancer interventions and improved patient care.

Exploring the recent developments of alginate silk fibroin material for hydrogel wound dressing: A review.

Hydrogels, a type of polymeric material capable of retaining water within a three-dimensional network, have demonstrated their potential in wound healing, surpassing traditional wound dressings. These hydrogels possess remarkable mechanical, chemical, and biological properties, making them suitable scaffolds for tissue regeneration. This article aims to emphasize the advantages of alginate, silk fibroin, and hydrogel-based wound dressings, specifically highlighting their crucial functions that accelerate the healing process of skin wounds. Noteworthy functions include self-healing ability, water solubility, anti-inflammatory properties, adhesion, antimicrobial properties, drug delivery, conductivity, and responsiveness to stimuli. Moreover, recent advancements in hydrogel technology have resulted in the development of wound dressings with enhanced features for monitoring wound progression, further augmenting their effectiveness. This review emphasizes the utilization of hydrogel membranes for treating excisional and incisional wounds, while exploring recent breakthroughs in hydrogel wound dressings, including nanoparticle composite hydrogels, stem cell hydrogel composites, and curcumin-hydrogel composites. Additionally, the review focuses on diverse synthesis procedures, designs, and potential applications of hydrogels in wound healing dressings.

Mesenchymal Stem Cells: From Regeneration to Drug Delivery Systems.

Targeting drug delivery has been a focus of researchers in recent years for cancer and other diseases. Many approaches such as liposomes, exosomes, nanoparticles (magnetic), encapsulation etc. have been developed and investigated for their clinical applications. But disadvantages linked to these therapies limit them to be used in clinical settings. Cell based drug delivery systems has emerged as an alternative for these therapies. Among cell types, mesenchymal stem cells (MSCs) proved to a potential cell type for research due to its many characteristics including low immunogenicity, chemotaxis and homing to tumor sites which are considered mandatory for drug delivery. This chapter focuses on the challenges and opportunities in using MSCs as therapeutic carrier of drugs in different ailments.

Multiepitope-Based Subunit Vaccine Design and Evaluation against Respiratory Syncytial Virus Using Reverse Vaccinology Approach.

Respiratory syncytial virus (RSV) is primarily associated with respiratory disorders globally. Despite the availability of information, there is still no competitive vaccine available for RSV. Therefore, the present study has been designed to develop a multiepitope-based subunit vaccine (MEV) using a reverse vaccinology approach to curb RSV infections. Briefly, two highly antigenic and conserved proteins of RSV (glycoprotein and fusion protein) were selected and potential epitopes of different categories (B-cell and T-cell) were identified from them. Eminently antigenic and overlapping epitopes, which demonstrated strong associations with their respective human leukocyte antigen (HLA) alleles and depicted collective ~70% coverage of the world's populace, were shortlisted. Finally, 282 amino acids long MEV construct was established by connecting 13 major histocompatibility complex (MHC) class-I with two MHC class-II epitopes with appropriate adjuvant and linkers. Adjuvant and linkers were added to increase the immunogenic stimulation of the MEV. Developed MEV was stable, soluble, non-allergenic, non-toxic, flexible and highly antigenic. Furthermore, molecular docking and molecular dynamics (MD) simulations analyses were carried out. Results have shown a firm and robust binding affinity of MEV with human pathogenic toll-like receptor three (TLR3). The computationally mediated immune response of MEV demonstrated increased interferon-γ production, a significant abundance of immunoglobulin and activation of macrophages which are essential for immune-response against RSV. Moreover, MEV codons were optimized and in silico cloning was performed, to ensure its increased expression. These outcomes proposed that the MEV developed in this study will be a significant candidate against RSV to control and prevent RSV-related disorders if further investigated experimentally.

Therapeutic Potential of Umbilical Cord Stem Cells for Liver Regeneration.

The liver is a vital organ for life and the only internal organ that is capable of natural regeneration. Although the liver has high regeneration capacity, excessive hepatocyte death can lead to liver failure. Various factors can lead to liver damage including drug abuse, some natural products, alcohol, hepatitis, and autoimmunity. Some models for studying liver injury are APAP-based model, Fas ligand (FasL), D-galactosamine/endotoxin (Gal/ET), Concanavalin A, and carbon tetrachloride-based models. The regeneration of the liver can be carried out using umbilical cord blood stem cells which have various advantages over other stem cell types used in liver transplantation. UCB-derived stem cells lack tumorigenicity, have karyotype stability and high immunomodulatory, low risk of graft versus host disease (GVHD), low risk of transmitting somatic mutations or viral infections, and low immunogenicity. They are readily available and their collection is safe and painless. This review focuses on recent development and modern trends in the use of umbilical cord stem cells for the regeneration of liver fibrosis.