Targeted delivery of miRNA based therapeuticals in the clinical management of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most aggressive (WHO grade IV) form of diffuse glioma endowed with tremendous invasive capacity. The availability of narrow therapeutic choices for GBM management adds to the irony, even the post-treatment median survival time is roughly around 14-16 months. Gene mutations seem to be cardinal to GBM formation, owing to involvement of amplified and mutated receptor tyrosine kinase (RTK)-encoding genes, leading to dysregulation of growth factor signaling pathways. Of-late, the role of different microRNAs (miRNAs) in progression and proliferation of GBM was realized, which lead to their burgeon potential applications for diagnostic and therapeutic purposes. miRNA signatures are intricately linked with onset and progression of GBM. Although, progression of GBM causes significant changes in the BBB to form BBTB, but still efficient passage of cancer therapeutics, including antibodies and miRNAs are prevented, leading to low bioavailability. Recent developments in the nanomedicine field provide novel approaches to manage GBM via efficient and brain targeted delivery of miRNAs either alone or as part of cytotoxic pharmaceutical composition, thereby modulating cell signaling in well predicted manner to promise positive therapeutic outcomes.

Nanotechnological based miRNA intervention in the therapeutic management of neuroblastoma.

Neuroblastoma (NB) is a widely diagnosed cancer in children, characterized by amplification of the gene encoding the MYCN transcription factor, which is highly predictive of poor clinical outcome and metastatic disease. microRNAs (a class of small non-coding RNAs) are regulated by MYCN transcription factor in neuroblastoma cells. The current research is focussed on identifying differential role of miRNAs and their interactions with signalling proteins, which are intricately linked with cellular processes like apoptosis, proliferation or metastasis. However, the therapeutic success of miRNAs is limited by pharmaco-technical issues which are well counteracted by nanotechnological advancements. The nanoformulated miRNAs unload anti-cancer drugs in a controlled and prespecified manner at target sites, to influence the activity of target protein in amelioration of NB. Recent advances and developments in the field of miRNAs-based systems for clinical management of NBs and the role of nanotechnology to overcome challenges with drug delivery of miRNAs have been reviewed in this paper.

Neuroinflammation: A Potential Risk for Dementia.

Dementia is a neurodegenerative condition that is considered a major factor contributing to cognitive decline that reduces independent function. Pathophysiological pathways are not well defined for neurodegenerative diseases such as dementia; however, published evidence has shown the role of numerous inflammatory processes in the brain contributing toward their pathology. Microglia of the central nervous system (CNS) are the principal components of the brain's immune defence system and can detect harmful or external pathogens. When stimulated, the cells trigger neuroinflammatory responses by releasing proinflammatory chemokines, cytokines, reactive oxygen species, and nitrogen species in order to preserve the cell's microenvironment. These proinflammatory markers include cytokines such as IL-1, IL-6, and TNFα chemokines such as CCR3 and CCL2 and CCR5. Microglial cells may produce a prolonged inflammatory response that, in some circumstances, is indicated in the promotion of neurodegenerative diseases. The present review is focused on the involvement of microglial cell activation throughout neurodegenerative conditions and the link between neuroinflammatory processes and dementia.

Role of triggering receptor expressed on myeloid cells 2 (TREM2) in neurodegenerative dementias.

Neurodegeneration is a debilitating condition that causes nerve cell degeneration or death. Neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and Lewy body dementia (LBD) are posing a larger population burden of dementia worldwide. Neurodegenerative dementia is one of the main challenges in public health with its main characteristics being permanent loss of memory, impairment in cognition, and impaired daily functions. The published literature about genetic studies of these disorders suggests genetic underpinning in the pathogenesis of neurodegenerative dementia. In the process of underlining the pathogenesis of NDD, growing evidence has related genetic variations in the triggering receptor expressed on myeloid cells 2 (TREM2). This review paper aims to provide a detailed information regarding the association of TREM2 and NDDs leading to dementia. A central consideration is AD that accounts for almost 50%-70% of all late-life dementias alone or in combination with other neurological disorders. Other prevalent neurodegenerative conditions that lead to dementia are also discussed. Such studies are important as they can give a comprehensive knowledge of TREM2's role in various NDDs, in order to maximize the potential for developing new therapeutic approaches.

Neuron-glia interactions: Molecular basis of alzheimer's disease and applications of neuroproteomics.

Neurodegenerative disorders present with progressive and irreversible degeneration of the neurons. Alzheimer's disease (AD) is one of the most common neurodegenerative disorders affecting 50 million people worldwide (2017), expected to be doubled every 20 years. Primarily affected by age, AD is the cause for old-age dementia, progressive memory loss, dysfunctional thoughts, confusion, cognitive impairment and personality changes. Neuroglia formerly understood as "glue" of the brain neurons consists of macroglia (astrocytes and oligodendrocyte), microglia and progenitors NG2-glia, and constitute a large fraction of the mammalian brain. The primary functions of glial cells are to provide neurons with metabolic and structural support in the healthy brain; however, they attain a "reactive" state from the "resting" state upon challenged with a pathological insult such as a neurodegenerative cascade. Failure or defects in their homoeostatic functions (i.e. concentration of ions, neurotransmitters) ultimately jeopardize neurons with excitotoxicity and oxidative stress. Moreover, the most common clinical outcome of AD is the cognitive impairment and memory loss, which are attributed mainly by the accumulation of Aß. Failure of glial cells to remove the Aß toxic proteins accelerates the AD progression. The rapidly emerging proteomic techniques such as mass spectrometry (MS), cross-linking mass spectrometry, hydrogen deuterium trade mass spectrometry, protein foot printing and 2-DGE combined with LC-MS/MS present wide array of possibilities for the identification of differentially expressed proteins in AD.

Lipid-based nanoformulations in the treatment of neurological disorders.

The neurological disorders affect millions of people worldwide, and are bracketed as the foremost basis of disability-adjusted life years (DALYs). The treatment options are symptomatic and often the movement of drugs is restricted by a specialized network of endothelial cell layers (adjoined by tight cell-to-cell junction proteins; occludin, claudins, and junctional adhesion molecules), pericytes and astroglial foot processes. In recent years, advances in nanomedicine have led to therapies that target central nervous system (CNS) pathobiology via altering signaling mechanisms such as activation of PI3K/Akt pathway in ischemic stroke arrests apoptosis, interruption of α-synuclein aggregation prevents neuronal degeneration in Parkinson's. Often such interactions are limited by insufficient concentrations of drugs reaching neuronal tissues and/or insufficient residence time of drug/s with the receptor. Hence, lipid nanoformulations, SLNs (solid lipid nanoparticles) and NLCs (nanostructured lipid carriers) emerged to overcome these challenges by utilizing physiological transport mechanisms across blood-brain barrier, such as drug-loaded SLN/NLCs adsorb apolipoproteins from the systemic circulation and are taken up by endothelial cells via low-density lipoprotein (LDL)-receptor mediated endocytosis and subsequently unload drugs at target site (neuronal tissue), which imparts selectivity, target ability, and reduction in toxicity. This paper reviews the utilization of SLN/NLCs as carriers for targeted delivery of novel CNS drugs to improve the clinical course of neurological disorders, placing some additional discussion on the metabolism of lipid-based formulations.

Off-label Medications Use in the Eastern Province of Saudi Arabia: The Views of General Practitioners, Pediatricians, and Other Specialists.

Background: Off-label drug prescribing remains a major pediatric health concern worldwide. The lack of studies in this vulnerable population causes many practitioners to prescribe drugs outside their license. This study aims to investigate and compare the current knowledge and views of general practitioners, pediatricians, and other specialists toward off-label pediatric prescribing. Methods: A descriptive, cross-sectional-based study conducted on a random sample of physicians who work in three different hospitals in the Eastern Province of Saudi Arabia. Results: Data were obtained from three hospitals, comprising a total of 160 practitioners. Overall, more than half of the participated practitioners (54%) were familiar with the definition of off-label prescribing. Thirty percentage of participated practitioners agreed that more than 10% of their prescribed medicines to children were off-labeled. A majority of participants expressed concerns over the efficacy (83%) and safety (92%) of off-label prescribing to children. Importantly, a noticeable proportion of the responders claimed that they sometimes observed an adverse drug reaction (n = 23; 20%) or treatment failure (n = 43; 37%) following off-label prescribing medicines to children. Only 46% participants have always informed the parents or guardian about the off-label prescription of medications to their children. Conclusion: A Large number of physicians are familiar with the concept of off-label prescribing of medicines to children in the Eastern Province of Saudi Arabia. Safety and efficacy are the main concerns of prescribing such medications. Policies toward improving pediatric clinical research and supporting the safety and efficacy of the drugs should be encouraged.

Paclitaxel-loaded Nanolipidic Carriers with Improved Oral Bioavailability and Anticancer Activity against Human Liver Carcinoma.

The poorly water-soluble chemotherapeutic agents, paclitaxel (PTX), exhibit serious clinical side effects upon oral administration due to poor aqueous solubility and a high degree of toxic effects due to non-specific distribution to healthy tissues. In our efforts, we formulated biocompatible dietary lipid-based nanostructured lipidic carriers (NLCs) to enhance the oral bioavailability of PTX for treatment of the liver cancer. A three-factor, three-level Box-Behnken design was employed for formulation and optimization of PTX-loaded NLC formulations. PTX-loaded NLC formulation prepared by melt-emulsification in which glyceryl monostearate (GMS) was used as solid lipid and soybean oil as liquid lipid, while poloxamer 188 and Tween 80 (1:1) incorporated as a surfactant. In vitro drug release investigation was executed by dialysis bag approach, which indicated initial burst effect with > 60% drug release within a 4-h time period. Moreover, PTX-NLCs indicated high entrapment (86.48%) and drug loading efficiency (16.54%). In vitro cytotoxicity study of PTX-NLCs performed on HepG2 cell line by MTT assay indicated that PTX-NLCs exhibited comparatively higher cytotoxicity than commercial formulation (Intaxel®). IC50 values of PTX-NLCs and Intaxel® after 24-h exposure were found to be 4.19 µM and 11.2 µM. In vivo pharmacokinetic study in Wistar rats also indicated nearly 6.8-fold improvement in AUC and Cmax of the drug from the PTX-NLCs over the PTX suspension. In a nutshell, the observed results construed significant enhancement in the biopharmaceutical attributes of PTX-NLCs as a potential therapy for the management of human liver carcinoma.

Nanosuspension-Based Aloe vera Gel of Silver Sulfadiazine with Improved Wound Healing Activity.

The present study focuses on the development and characterization of nanosuspension of a poorly soluble drug, silver sulfadiazine (SSD) incorporated in Aloe vera gel (AV-gel) for improving its therapeutic efficacy. The SSD solution in ammonia was subjected to nanoprecipitation in surfactant solution and particle size was optimized by varying concentration of surfactant. Optimized formulation constituted of 5.5% (w/v) Span 20 and 5.5% (w/v) Tween 80 as a dispersing agent and 0.5% (w/v) Poloxamer 188 as a co-surfactant. The prepared nanosuspension was evaluated for particle size, polydispersity index, surface morphology, and x-ray diffraction study. The optimized nanosuspension was incorporated into nanogel formulation with the addition of 1% AV-gel and 0.5% Carbopol 940 for topical delivery of nanosized SSD. Evaluation of in vitro drug release exhibited a significant enhancement in release rate of the drug from developed nanogel formulation (77.16 ± 3.241%) in comparison to marketed formulation (42.81 ± 1.452%) after 48 h. In vivo histopathological studies in rats for 14 days of application of prepared nanogel showed improvement in the wound healing potential as compared to marketed formulation.

Nanogels as Drug Delivery Carrier: A Narrative Review on Formulation Techniques, Characterization, Applications, and Patents.

Under the umbrella of targeted drug delivery systems, several techniques are unleashed in the market that allow a drug or other pharmacologically active material to be delivered to the target cell to treat a condition or health problem. The improvement of the pharmaceutical delivery systems' effectiveness, safety, and stability is accomplished through the Formulation of the nano-gel-based delivery system. Nanogels are aqueous dispersions of submicronsized, three-dimensional, strongly cross-linked networks of hydrophilic polymers that are inflated by water. Through a variety of delivery routes, such as oral, pulmonary, nasal, parenteral, and intraocular, an active pharmaceutical agent or therapeutic agent with a high or low molecular weight can be easily encapsulated into nanogels. Nanogels have been researched as drug delivery systems due to their beneficial qualities, such as biocompatibility, high stability, flexible particle size, drug loading capacity, and potential surface modification for active targeting by attaching ligands that recognize cognate receptors on target cells or tissues. By responding to internal or external stimuli, including pH, temperature, light, and redox, nano gels can be made to be stimulus-responsive, allowing for regulated drug release. Thus, in the fact of said characteristics' of nano gels, this review manuscript aims to provide an overview of characterization, evaluation, formulation technique, recent applications, and patents of nano gels.

Green Synthesis of Silver Nanoparticles and their Potential Applications in Mitigating Cancer.

In recent years, the field of nanotechnology has brought about significant advancements that have transformed the landscape of disease diagnosis, prevention, and treatment, particularly in the realm of medical science. Among the various approaches to nanoparticle synthesis, the green synthesis method has garnered increasing attention. Silver nanoparticles (AgNPs) have emerged as particularly noteworthy nanomaterials within the spectrum of metallic nanoparticles employed for biomedical applications. AgNPs possess several key attributes that make them highly valuable in the biomedical field. They are biocompatible, cost-effective, and environmentally friendly, rendering them suitable for various bioengineering and biomedical applications. Notably, AgNPs have found a prominent role in the domain of cancer diagnosis. Research investigations have provided evidence of AgNPs' anticancer activity, which involves mechanisms such as DNA damage, cell cycle arrest, induction of apoptosis, and the regulation of specific cytokine genes. The synthesis of AgNPs primarily involves the reduction of silver ions by reducing agents. Interestingly, natural products and living organisms have proven to be effective sources for the generation of precursor materials used in AgNP synthesis. This comprehensive review aims to summarize the key aspects of AgNPs, including their characterization, properties, and recent advancements in the field of biogenic AgNP synthesis. Furthermore, the review highlights the potential applications of these nanoparticles in combating cancer.

Phytochemicals and Nanotechnology: A Powerful Combination against Breast Cancer.

Considerable advancements have been made in breast cancer therapeutics in the past few decades. However, the advent of chemo-resistance and adverse drug reactions coupled with tumor metastasis and recurrence posed a serious threat to combat this lethal disease. Novel anti-cancer agents, as well as new therapeutic strategies, are needed to complement conventional breast cancer therapies. The quest for developing novel anti-cancer drugs caused an upsurge in exploring and harnessing natural compounds, especially phytochemicals. Various research groups have explored and documented the anti-cancer potential of wide variety of phytochemical groups including flavonoids (curcumin, kaempferol, myricetin, quercetin, naringenin, apigenin, genistein epigallocatechin gallate), stilbenes (resveratrol), carotenoids (crocin, lycopene, lutein), and anthraquinone (Emodin). However, low chemical stability, poor water solubility, and short systemic half-life impede their clinical utility. The implication of nano-technological approaches to decode the pharmacokinetic challenges associated with phytochemical usage, as well as selective drug targeting, have markedly enhanced the pre-clinical anti-cancer activity, thus aiding in their clinical translation. This review documented the recent advances in utilizing phytochemicals for breast cancer prevention and lipidbased nanotechnological approaches for circumventing their pharmacokinetic concerns to enhance their systemic availability, cytotoxicity, and targeted delivery against breast cancer alone as well as in combination with conventional therapeutic agents.

Sulfadiazine Exerts Potential Anticancer Effect in HepG2 and MCF7 Cells by Inhibiting TNFα, IL1b, COX-1, COX-2, 5-LOX Gene Expression: Evidence from In Vitro and Computational Studies.

Drug repurposing is a promising approach that has the potential to revolutionize the drug discovery and development process. By leveraging existing drugs, we can bring new treatments to patients more quickly and affordably. Anti-inflammatory drugs have been shown to target multiple pathways involved in cancer development and progression. This suggests that they may be more effective in treating cancer than drugs that target a single pathway. Cell viability was measured using the MTT assay. The expression of genes related to inflammation (TNFa, IL1b, COX-1, COX-2, and 5-LOX) was measured in HepG2, MCF7, and THLE-2 cells using qPCR. The levels of TNFα, IL1b, COX-1, COX-2, and 5-LOX were also measured in these cells using an ELISA kit. An enzyme binding assay revealed that sulfadiazine expressed weaker inhibitory activity against COX-2 (IC50 = 5.27 µM) in comparison with the COX-2 selective reference inhibitor celecoxib (COX-2 IC50 = 1.94 µM). However, a more balanced inhibitory effect was revealed for sulfadiazine against the COX/LOX pathway with greater affinity towards 5-LOX (IC50 = 19.1 µM) versus COX-1 (IC50 = 18.4 µM) as compared to celecoxib (5-LOX IC50 = 16.7 µM, and COX-1 IC50 = 5.9 µM). MTT assays revealed the IC50 values of 245.69 ± 4.1 µM and 215.68 ± 3.8 µM on HepG2 and MCF7 cell lines, respectively, compared to the standard drug cisplatin (66.92 ± 1.8 µM and 46.83 ± 1.3 µM, respectively). The anti-inflammatory effect of sulfadiazine was also depicted through its effect on the levels of inflammatory markers and inflammation-related genes (TNFα, IL1b, COX-1, COX-2, 5-LOX). Molecular simulation studies revealed key binding interactions that explain the difference in the activity profiles of sulfadiazine compared to celecoxib. The results suggest that sulfadiazine exhibited balanced inhibitory activity against the 5-LOX/COX-1 enzymes compared to the selective COX-2 inhibitor, celecoxib. These findings highlight the potential of sulfadiazine as a potential anticancer agent through balanced inhibitory activity against the COX/LOX pathway and reduction in the expression of inflammatory genes.

Cannabis Sativa in Phytotherapy: Reappraisal of Therapeutic Potential and Regulatory Aspects.

Cannabis sativa is widely used as a folk medicine in many parts of the globe and has been reported to be a treasure trove of phytoconstituents, including cannabinoids, terpenoids, and flavonoids. Accumulating evidence from various pre-clinical and clinical studies revealed the therapeutic potential of these constituents in various pathological conditions, including chronic pain, inflammation, neurological disorders, and cancer. However, the psychoactive effect and addiction potential associated with cannabis use limited its clinical application. In the past two decades, extensive research on cannabis has led to a resurgence of interest in the clinical application of its constituents, particularly cannabinoids. This review summarizes the therapeutic effect and molecular mechanism of various phytoconstituents of cannabis. Furthermore, recently developed nanoformulations of cannabis constituents have also been reviewed. Since cannabis is often associated with illicit use, regulatory aspects are of vital importance and this review therefore also documented the regulatory aspects of cannabis use along with clinical data and commercial products of cannabis.

Nutraceuticals and their Derived Nano-Formulations for the Prevention and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the common chronic neurological disorders and associated with cognitive dysfunction, depression and progressive dementia. The presence of ß-amyloid or senile plaques, hyper-phosphorylated tau proteins, neurofibrillary tangle, oxidative-nitrative stress, mitochondrial dysfunction, endoplasmic reticulum stress, neuroinflammation and derailed neurotransmitter status are the hallmarks of AD. Currently, donepezil, memantine, rivastigmine and galantamine are approved by the FDA for symptomatic management. It is well-known that these approved drugs only exert symptomatic relief and possess poor patient-compliance. Additionally, various published evidence showed the neuroprotective potential of various nutraceuticals via their antioxidant, anti-inflammatory and anti-apoptotic effects in the preclinical and clinical studies. These nutraceuticals possess a significant neuroprotective potential and hence, can be a future pharmacotherapeutic for the management and treatment of AD. However, nutraceuticals suffer from certain major limitations such as poor solubility, low bioavailability, low stability, fast hepatic- metabolism and larger particle size. These pharmacokinetic attributes restrict their entry into the brain via the blood-brain barrier. Therefore, to overcome such issues, various nanoformulations of nutraceuticals have been developed, that allow their effective delivery into the brain owing to reduced particle size, increased lipophilicity, increased bioavailability and avoidance of fast hepatic metabolism. Thus, in this review, we have discussed the etiology of AD, focusing on the pharmacotherapeutics of nutraceuticals with preclinical and clinical evidence, discussed pharmaceutical limitations and regulatory aspects of nutraceuticals to ensure safety and efficacy. We have further explored various nanoformulations of nutraceuticals as a novel approach to overcome the existing pharmaceutical limitations and for effective delivery into the brain.

Recent Advancements in CNS Acting Drugs: A Step Towards End of Illness.

Progressive degeneration in the morphology and functions of neuronal cells leads to multifactorial pathogenesis conditions of oxidative stress, mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation to mediate heterogeneous types of neurodegenerative diseases, such as Epilepsy, Alzheimer's (AD) and Parkinson's (PD), more prominently among aging populations. In this editorial, complex mechanisms, challenges, and advancements made in the discovery of new neurotherapeutics, as well as designing approaches being adopted to fabricate brain-targeted delivery systems, are discussed.

Nanotechnological Approaches for the Treatment of Triple-Negative Breast Cancer: A Comprehensive Review.

Breast cancer is the most prevalent cancer in women around the world, having a sudden spread nowadays because of the poor sedentary lifestyle of people. Comprising several subtypes, one of the most dangerous and aggressive ones is triple-negative breast cancer or TNBC. Even though conventional surgical approaches like single and double mastectomy and preventive chemotherapeutic approaches are available, they are not selective to cancer cells and are only for symptomatic treatment. A new branch called nanotechnology has emerged in the last few decades that offers various novel characteristics, such as size in nanometric scale, enhanced adherence to multiple targeting moieties, active and passive targeting, controlled release, and site-specific targeting. Among various nanotherapeutic approaches like dendrimers, lipid-structured nanocarriers, carbon nanotubes, etc., nanoparticle targeted therapeutics can be termed the best among all for their specific cytotoxicity to cancer cells and increased bioavailability to a target site. This review focuses on the types and molecular pathways involving TNBC, existing treatment strategies, various nanotechnological approaches like exosomes, carbon nanotubes, dendrimers, lipid, and carbon-based nanocarriers, and especially various nanoparticles (NPs) like polymeric, photodynamic, peptide conjugated, antibody-conjugated, metallic, inorganic, natural product capped, and CRISPR based nanoparticles already approved for treatment or are under clinical and pre-clinical trials for TNBC.

WITHDRAWN: Cannabis Sativa In Phytotherapy : Reappraisal Of Therapeutic Potential And Regulatory Aspects

The article has been withdrawn at the request of the editor of the journal Current Pharmaceutical Biotechnology.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

An Overview and Therapeutic Promise of Nutraceuticals Against Sports-Related Brain Injury.

Sports-related traumatic brain injury (TBI) is one of the common neurological maladies experienced by athletes. Earlier, the term 'punch drunk syndrome' was used in the case TBI of boxers and now this term is replaced by chronic traumatic encephalopathy (CTE). Sports-related brain injury can either be short-term or long-term. A common instance of brain injury encompasses subdural hematoma, concussion, cognitive dysfunction, amnesia, headache, vision issue, axonopathy, or even death, if it remains undiagnosed or untreated. Further, chronic TBI may lead to pathogenesis of neuroinflammation and neurodegeneration via tauopathy, the formation of neurofibrillary tangles, and damage to the blood-brain barrier, microglial, and astrocyte activation. Thus, altered pathological, neurochemical, and neurometabolic attributes lead to the modulation of multiple signaling pathways and cause neurological dysfunction. Available pharmaceutical interventions are based on one drug one target hypothesis and are thereby unable to cover altered multiple signaling pathways. However, in recent times, pharmacological intervention of nutrients and nutraceuticals have been explored as they exert a multifactorial mode of action and maintain over homeostasis of the body. There are various reports available showing the positive therapeutic effect of nutraceuticals in sport-related brain injury. Therefore, in the current article, we have discussed the pathology, neurological consequence, sequelae, and perpetuation of sports-related brain injury. Further, we have discussed various nutraceutical supplements as well as available animal models to explore the neuroprotective effect/ upshots of these nutraceuticals in sports-related brain injury.

Structural Activity Relationship based Medicinal Perspectives of Pyrimidine Derivatives as Anti-Alzheimer's Agents: A Comprehensive Review.

Pyrimidine is an aromatic and heterocyclic organic compound containing a 6-membered ring consisting of four carbon and two nitrogen atoms on alternative positions. Pyrimidine scaffolds described their existence in the medicinal chemist's cause for their synthesizing practicability and nonpoisonous nature. However, the reason behind neurological disorders is still an open challenge for scientific research and development organizations. Efficacy voids are widespread before researchers, despite high throughput research in the field of anti-Alzheimer's drugs.Researchers have constantly investigated all the probabilities for restraining the unwanted adverse effects of the anti-Alzheimer's agents and are focusing more extensively to rehabilitate neurological disorders. The scientific literature on drug development has been an aspiration to medicinal chemists and other researchers to facilitate further research. Therefore, this review emphasizes the structure-activity relationship (SAR) based approach and the pharmacological advancements of pyrimidine moiety in the new era of therapeutics as anti-Alzheimer's agents.