Divya Jindal

Background: According to the WHO projections globally, dementia has afflicted roughly 55 million people worldwide by 2022, with 10 million new cases being identified every year. Thus, from this data information, we can conclude that central nervous system (CNS) disorders are becoming more common and prevalent worldwide. And amongst all CNS‐related diseases, one of the most concerning aspects is the prevalence of Alzheimer’s disease which has become the most common trait in the world’s ageing population. AD is also known as the most challenging kind of dementia to cure. Pathologically in AD, the static loss of cortical neurons causes the deterioration of neuronal connections and circuits, which results in a range of progressive neocortical degeneration linked to the buildup of Aβ plaques. It is challenging to treat AD due to a number of inescapable physiological limits, including circulation blockages, medication permeability and degradation, and other factors. As a result, the drug’s capacity to reach the brain’s afflicted regions is restricted, and the CNS is unable to absorb therapeutic molecules passively.Method: Therefore, the idea of nanotherapeutics has evolved into a feasible technique for CNS‐based drug delivery. In our research, we computationally assessed the efficacy of the traditionally renowned Indian Ayurvedic medicinal plants Bacopa monnieri and Withania somnifera, used for their capacity to provide neuroprotective effects, especially in the case of CNS disorders. After being altered to achieve the nanometric size range, they were then created for the nano‐emulsions system.Result: According to the computational findings, synthetic extracts had a higher binding affinity for CNS‐related biomarkers than conventional medicines. Subsequently, using an aqueous titration approach, an oil‐in‐water (o/w) nano‐emulsion system was devised for Withania somnifera and Bacopa monnieri standard extracts in suitable and optimized excipients (Almond oil, Triacetin, Ethanol). The nanometric size range (100‐300 nm) of the optimized nanoformulations showed a substantially higher level of neuroprotective potential than their extracts, according to the characterization results.Conclusion: In conclusion, the present study demonstrates that the developed formulation has potential therapeutic effects on improving the pathological state of AD, and might be taken further as a promising candidate for clinical research to evaluate its efficacy in human.

Background: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) plays a crucial role in regulating lipid and glucose metabolism, cancer, and inflammation, making it an attractive target for drug development. Meanwhile, β-Carotene, known for its antioxidant, anticancer and antiinflammatory properties, holds promise for modulating PPAR-γ activity. Understanding their interaction is crucial. Objective: This study aims to explore the therapeutic potential of β-carotene in modulating PPAR-γ activity by investigating their binding interactions. Methods: Screening of bioactive compounds from PubChem was conducted using GlideXP to identify potential PPAR-γ (PDB: 2PRG) ligands. During this screening, both protein and bioactive compounds were prepared following established protocols. Subsequently, the compounds were docked into the ligand binding domain (LBD) of the protein using XP docking. Rosiglitazone was used as an internal control. β-Carotene emerged as a lead based on Lipinski’s rule, docking score, free energy, and LBD interactions. Molinspiration analysis assessed its drug likeness. Molecular dynamics (MD) simulations utilizing Desmond with OPLS 2005 force field were employed to examine the dynamics and stability of the PPAR-γ/β-carotene complex. Results: β-carotene had strong hydrophobic interactions with specific residues within the ligandbinding domain of PPAR-γ. The calculated binding affinity (-9.07 kcal/mol) indicated a strong interaction between β-carotene and PPAR-γ, suggesting that β-carotene may modulate the activity of PPAR-γ. On a time scale of 100 ns, the MD simulations provided insights into the conformational changes, flexibility, and intermolecular interactions within the complex. Conclusion: In silico docking and dynamics simulation analyses show that PPAR-γ and β-carotene can form a stable complex, suggesting potential implications for metabolic modulation.

Background: Alzheimer’s disease (AD) is one of the world’s most debilitating diseases, affecting over 24 million people worldwide. Many synthetic medications developed for Alzheimer’s disease were ineffective in treating the disease, however, they were able to control the symptoms to some extent. As a result, effective bioactive chemicals are in high demand. Bacopa monnieri is an Indian herb that has been used to treat a variety of neurological disorders, according to artifacts and literature (NDDs). We want to find bioactive molecules that target distinct indicators involved in the Alzheimer’s hypothesis. The goal of this study was to learn more about Bacopa monnieri’s potential to combat various AD targets.Method: The research involved the in‐silico approach by performing docking studies of all bioactive compounds of Bacopa monnieri and target AChE, BuChE, MAO‐A, BACE1, NMDA & APOE. All the ligands of extract were selected from the database and the protein along with ligand were prepared and docking was performed using the Glide module of Schrodinger. Further, the free energy of the complex was calculated using the MM‐GBSA of the prime module. ADME and Bioactivity scores were also analyzed for further understanding.Result: The results demonstrate free binding and free complex energies for all the phytocompounds of Bacopa monnieri. MAO‐A, AChE, BuChE, and NMDA have shown greater binding affinities than the respective controls. The good scoring compounds were further checked for their Free Energy calculations to ensure their stability. The ADMET properties and bioactivity scores revealed the best stability of the compounds in the human system.Conclusion: The results of the study indicated that the formulations of Bacopa monnieri can be one of the potent therapeutic components against AChE, BuChE, MAO‐A, BACE1, NMDA & APOE, based on the docking scores, free energies, amino acid interactions, ADME, bioactivity, and toxicity. Amongst all, key compounds that showed good binding energies compared to controls for all the targets were L‐Arabinose, DL‐Aspartic acid, L‐Ascorbic acid, DL‐Alanine, and 2,3‐dimethylaniline. Henceforth, it is an effective therapeutic candidate for AD.

The vast use of corticosteroids (CCSs) globally has led to an increase in CCS-induced neuropsychiatric disorders (NPDs), a very common manifestation in patients after CCS consumption. These neuropsychiatric disorders range from depression, insomnia, and bipolar disorders to panic attacks, overt psychosis, and many other cognitive changes in such subjects. Though their therapeutic importance in treating and improving many clinical symptoms overrides the complications that arise after their consumption, still, there has been an alarming rise in NPD cases in recent years, and they are seen as the greatest public health challenge globally; therefore, these potential side effects cannot be ignored. It has also been observed that many of the neuronal functional activities are regulated and controlled by genomic variants with epigenetic factors (DNA methylation, non-coding RNA, and histone modeling, etc.), and any alterations in these regulatory mechanisms affect normal cerebral development and functioning. This study explores a general overview of emerging concerns of CCS-induced NPDs, the effective molecular biology approaches that can revitalize NPD therapy in an extremely specialized, reliable, and effective manner, and the possible gene-editing-based therapeutic strategies to either prevent or cure NPDs in the future.

Glioblastoma multiforme (GBM) is known as the most aggressive and prevalent brain tumor with a high mortality rate. It is reported in people who are as young as 10 years old to as old as over 70 years old, exhibiting inter and intra tumor heterogeneity. There are several genomic and proteomic investigations that have been performed to find the unexplored potential targets of the drug against GBM. Therefore, certain effective targets have been taken to further validate the studies embarking on the robustness in the field of medicinal chemistry followed by testing in clinical trials. Also, The Cancer Genome Atlas (TCGA) project has identified certain overexpressed targets involved in the pathogenesis of GBM in three major pathways, i.e., tumor protein 53 (p53), retinoblastoma (RB), and receptor tyrosine kinase (RTK)/rat sarcoma virus (Ras)/phosphoinositide 3-kinase (PI3K) pathways. This review focuses on the compilation of recent developments in the fight against GBM thus, directing future research into the elucidation of pathogenesis and potential cure for GBM. Also, it highlights the potential biomarkers that have undergone extensive research and have promising prognostic and predictive values. Additionally, this manuscript analyses the advent of gene therapy and immunotherapy, unlocking the way to consider treatment approaches other than, or in addition to, conventional chemo-radiation therapies. This review study encompasses all the relevant research studies associated with the pathophysiology, occurrence, diagnostic tools, and therapeutic intervention for GBM. It highlights the evolution of various therapeutic perspectives against GBM from the most conventional form of radiotherapy to the recent advancement of gene/cell/immune therapy. Further, the review focuses on various targeted therapies for GBM including chemotherapy sensitization, radiotherapy, nanoparticles based, immunotherapy, cell therapy, and gene therapy which would offer a comprehensive account for exploring several facets related to GBM prognostics.

The pathogenesis of COVID-19 is complicated by immune dysfunction. The impact of immune-based therapy in COVID-19 patients has been well documented, with some notable studies on the use of anti-cytokine medicines. However, the complexity of disease phenotypes, patient heterogeneity and the varying quality of evidence from immunotherapy studies provide problems in clinical decision-making. This review seeks to aid therapeutic decision-making by giving an overview of the immunological responses against COVID-19 disease that may contribute to the severity of the disease. We have extensively discussed theranostic methods for COVID-19 detection. With advancements in technology, bioinformatics has taken studies to a higher level. The paper also discusses the application of bioinformatics and machine learning tools for the diagnosis, vaccine design and drug repurposing against SARS-CoV-2.