A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer's Disease Risk in Older Men with Prostate Cancer.

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer's disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aß) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aß oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

A comprehensive update on genetic inheritance, epigenetic factors, associated pathology, and recent therapeutic intervention by gene therapy in schizophrenia.

Schizophrenia is a severe psychological disorder in which reality is interpreted abnormally by the patient. The symptoms of the disease include delusions and hallucinations, associated with extremely disordered behavior and thinking, which may affect the daily lives of the patients. Advancements in technology have led to understanding the dynamics of the disease and the identification of the underlying causes. Multiple investigations prove that it is regulated genetically, and epigenetically, and is affected by environmental factors. The molecular and neural pathways linked to the regulation of schizophrenia have been extensively studied. Over 180 Schizophrenic risk loci have now been recognized due to several genome-wide association studies (GWAS). It has been observed that multiple transcription factors (TF) binding-disrupting single nucleotide polymorphisms (SNPs) have been related to gene expression responsible for the disease in cerebral complexes. Copy number variation, SNP defects, and epigenetic changes in chromosomes may cause overexpression or underexpression of certain genes responsible for the disease. Nowadays, gene therapy is being implemented for its treatment as several of these genetic defects have been identified. Scientists are trying to use viral vectors, miRNA, siRNA, and CRISPR technology. In addition, nanotechnology is also being applied to target such genes. The primary aim of such targeting was to either delete or silence such hyperactive genes or induce certain genes that inhibit the expression of these genes. There are challenges in delivering the gene/DNA to the site of action in the brain, and scientists are working to resolve the same. The present article describes the basics regarding the disease, its causes and factors responsible, and the gene therapy solutions available to treat this disease.

Molecular Docking and Network Pharmacology Interaction Analysis of Gingko Biloba (EGB761) Extract with Dual Target Inhibitory Mechanism in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common type of neurodegenerative dementia affecting people in their later years of life. The AD prevalence rate has significantly increased due to a lack of early detection technology and low therapeutic efficacy. Despite recent scientific advances, some aspects of AD pathological targets still require special attention. Certain traditionally consumed phytocompounds have been used for thousands of years to treat such pathologies. The standard extract of Gingko biloba (EGB761) is a combination of 13 macro phyto-compounds and various other micro phytocompounds that have shown greater therapeutic potential against the pathology of AD. OBJECTIVE: Strong physiological evidence of cognitive health preservation has been observed in elderly people who keep an active lifestyle. According to some theories, consuming certain medicinal extracts helps build cognitive reserve. We outline the research employing EGB761 as a dual target for AD. METHODS: This study investigates various inhibitory targets against AD using computational approaches such as molecular docking, network pharmacology, ADMET (full form), and bioactivity prediction of the selected compounds. RESULTS: After interaction studies were done for all the phytoconstituents of EGB761, it was concluded that all four of the phytocompounds (kaempferol, isorhamnetin, quercetin, and ginkgotoxin) showed the maximum inhibitory activity against acetylcholinesterase (AChE) and GSK3ß. CONCLUSION: The highly active phytocompounds of EGB761, especially quercetin, kaempferol, and isorhamnetin, have better activity against AChE and GSK3ß than its reported synthetic drug, according to molecular docking and network pharmacology research. These compounds may act on multiple targets in the protein network of AD. The AChE theory was primarily responsible for EGB761's therapeutic efficacy in treating AD.

Recent Updates on Corticosteroid-Induced Neuropsychiatric Disorders and Theranostic Advancements through Gene Editing Tools.

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.

New phase therapeutic pursuits for targeted drug delivery in glioblastoma multiforme.

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.

Current theranostic approaches for metastatic cancers through hypoxia-induced exosomal packaged cargo.

Tumour cells exhibit numerous defence mechanisms against various therapeutic strategies and help in developing drug resistance. These defence strategies help cancer cells prevent their elimination from an organism and prosper at a specific location. In recent times it's been observed that there is a significant contribution of secreted extracellular vesicles (EVs) from such tumorigenic sites in the development and prognosis of cancer. Amongst the various types of EVs, exosomes behave like biological carriers, play a crucial role in transporting the content between different cells, and had such an underrated defence mode by getting induced due to the hypoxia secreted highly specialised double-membrane structures. These small structure vesicles play a critical part in regulating local microenvironment and intracellular communications, cited by many research studies. Exosomes are a potential carrier of several cargo biomolecules like proteins, lipids, miRNAs, mRNAs etc., facilitating better communication within the microenvironment of cancer cells, enhancing the metastatic rate along with cancer progression. Several studies have extensively researched elucidating exosomes mediated radiation-induced bystander effects: multidrug resistance, epithelial-mesenchymal transition, and help cancer cells escape from the immune system apart from playing a critical role in angiogenesis too. Due to its natural tendency to carry different biomolecules, it can also be used to haul chemical drugs and efficiently deliver the drug molecules to the targeted site of cancer. The current review aims to explore the vivid role of hypoxia-induced exosomes in tumour progression along with its application and challenges in cancer therapeutics.

Neuroprotective Ability of Apocynin Loaded Nanoparticles (APO-NPs) as NADPH Oxidase (NOX)-Mediated ROS Modulator for Hydrogen Peroxide-Induced Oxidative Neuronal Injuries.

Apocynin (APO) is a known multi-enzymatic complexed compound, employed as a viable NADPH oxidase (NOX) inhibitor, extensively used in both traditional and modern-day therapeutic strategies to combat neuronal disorders. However, its therapeutic efficacy is limited by lower solubility and lesser bioavailability; thus, a suitable nanocarrier system to overcome such limitations is needed. The present study is designed to fabricate APO-loaded polymeric nanoparticles (APO-NPs) to enhance its therapeutic efficacy and sustainability in the biological system. The optimized APO NPs in the study exhibited 103.6 ± 6.8 nm and -13.7 ± 0.43 mV of particle size and zeta potential, respectively, along with further confirmation by TEM. In addition, the antioxidant (AO) abilities quantified by DPPH and nitric oxide scavenging assays exhibited comparatively higher AO potential of APO-NPs than APO alone. An in-vitro release profile displayed a linear diffusion pattern of zero order kinetics for APO from the NPs, followed by its cytotoxicity evaluation on the PC12 cell line, which revealed minimal toxicity with higher cell viability, even after treatment with a stress inducer (H2O2). The stability of APO-NPs after six months showed minimal AO decline in comparison to APO only, indicating that the designed nano-formulation enhanced therapeutic efficacy for modulating NOX-mediated ROS generation.

In-Silico Validation and Fabrication of Matrix Diffusion-Based Polymeric Transdermal Patches for Repurposing Gabapentin Hydrochloride in Neuropathic Pain.

BACKGROUND: Gabapentin (GBP) is an FDA-approved drug for the treatment of partial and secondary generalized seizures, apart from being used for diabetic neuropathic pain. GBP displays a highly intricate mechanism of action and its inhibitory response in elevated antagonism of NMDA (N-methyl-D-aspartate receptor) receptor and thus, can be repurposed for controlling neuropathic pain. OBJECTIVE: Therefore, in the present study, we have selected hBCATc (humanPyridoxal 5'-phosphate- dependent branched-chain aminotransferase cytosolic) gene that is highly expressed in silico validation through neuropathic stressed conditions. Thereafter, have analysed the GBP as its competitive inhibitor by in silico validation through homology modelling, molecular docking, also predicting its structural alerts and pharmacokinetic suitability through ADMET. However, and GBP was found to be a potential drug in controlling neuropathic pain, still, it has certain critical and pharmacokinetic limitations; therefore, the need for its targeted delivery was required, and the same was attained by designing a GBP loaded transdermal patch (GBP-TDP). METHODS: A suitable and equally efficacious GBP - TDP was developed by a solvent evaporation method using PVP and HPMC in the ratio of 2:1 as a polymer base for reservoir type of TDP. Also, PEG 400 was used as a plasticizer, and PVA (4%) was taken for backing membrane preparation, and then the optimized GBP-TDP was subjected for physical characterization, optimization and ex vivo release kinetics. RESULTS: The results showed desired specifications with uneven and flaky surface appearance giving an avenue for controlled release of the drugs with 92.34 ± 1.43% of drug release in 10 hours, further suggesting that GBP-TDP can be used as an effective tool against diabetic neuropathy pain. CONCLUSION: In this study, we have repurposed Gabapentin to treat diabetic neuropathy and validated the same by conducting a detailed in silico evaluation starting from homology Modelling of the target protein hBCATc, cross verified by the Ramachandran plot analysis with the most favoured region of 92.1% (encompassing 303 residues out of 386).