DNA Sequencing Technologies and DNA Barcoding.

DNA barcodes are short, standardized DNA segments that geneticists can use to identify all living taxa. On the other hand, DNA barcoding identifies species by analyzing these specific regions against a DNA barcode reference library. In its initial years, DNA barcodes sequenced by Sanger's method were extensively used by taxonomists for the characterization and identification of species. But in recent years, DNA barcoding by next-generation sequencing (NGS) has found broader applications, such as quality control, biomonitoring of protected species, and biodiversity assessment. Technological advancements have also paved the way to metabarcoding, which has enabled massive parallel sequ.encing of complex bulk samples using high-throughput sequencing techniques. In future, DNA barcoding along with high-throughput techniques will show stupendous progress in taxonomic classification with reference to available sequence data.

Neuroepigenetics of ageing and neurodegeneration-associated dementia: An updated review.

Gene expression is tremendously altered in the brain during memory acquisition, recall, and forgetfulness. However, non-genetic factors, including environmental elements, epigenetic changes, and lifestyle, have grabbed significant attention in recent years regarding the etiology of neurodegenerative diseases (NDD) and age-associated dementia. Epigenetic modifications are essential in regulating gene expression in all living organisms in a DNA sequence-independent manner. The genes implicated in ageing and NDD-related memory disorders are epigenetically regulated by processes such as DNA methylation, histone acetylation as well as messenger RNA editing machinery. The physiological and optimal state of the epigenome, especially within the CNS of humans, plays an intricate role in helping us adjust to the changing environment, and alterations in it cause many brain disorders, but the mechanisms behind it still need to be well understood. When fully understood, these epigenetic landscapes could act as vital targets for pharmacogenetic rescue strategies for treating several diseases, including neurodegeneration- and age-induced dementia. Keeping this objective in mind, this updated review summarises the epigenetic changes associated with age and neurodegeneration-associated dementia.

Therapeutic potential of lipid nanosystems for the treatment of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The degeneration of dopaminergic neurons in the midbrain is primarily responsible for the onset of the disease. The major challenge faced in the treatment of PD is the blood-brain barrier (BBB), which impedes the delivery of therapeutics to targeted locations. To address this issue, lipid nanosystems have been used for the precise delivery of therapeutic compounds in anti-PD therapy. In this review, we will discuss the application and clinical significance of lipid nanosystem in delivering therapeutic compounds for anti-PD treatment. These medicinal compounds include ropinirole, apomorphine, bromocriptine, astaxanthin, resveratrol, dopamine, glyceryl monooleate, levodopa, N-3,4-bis(pivaloyloxy)- dopamine and fibroblast growth factor, which have significant potential to treat PD in the early stage. This review, in a nutshell, will pave the way for researchers to develop diagnostic and potential therapeutic approaches using nanomedicine to overcome the challenges posed by the BBB in delivering therapeutic compounds for PD.

Pharmaceutical prospects of Silymarin for the treatment of neurological patients: an updated insight.

Background: Silymarin is a polyphenolic flavonoid complex extricated from dried fruits and seeds of the plant Silybum marianum L. Chemically, it is a mixture of flavonolignan complexes consisting of silybin, isosilybin, silychristin, silydianin, a minor quantity of taxifolin, and other polyphenolic compounds, which possess different bio medicinal values. Purpose: This review critically looks into the current status, pharmaceutical prospects and limitations of the clinical application of Silymarin for treating neurological disorders. In particular, Silymarin's medicinal properties and molecular mechanisms are focused on providing a better-compiled understanding helpful in its neuro-pharmacological or therapeutic aspects. Methods: This review was compiled by the literature search done using three databases, i.e., PubMed (Medline), EMBASE and Science Direct, up to January 2023, using the keywords-Silymarin, neurological disorders, cognitive disorders, Type 2 Diabetes, pharmaceutical prospects and treatment. Then, potentially relevant publications and studies (matching the eligible criteria) were retrieved and selected to explain in this review using PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) study flow chart. Result: Since its discovery, it has been widely studied as a hepatoprotective drug for various liver disorders. However, in the last 10-15 years, several research studies have shown its putative neuroprotective nature against various brain disorders, including psychiatric, neurodegenerative, cognitive, metabolic and other neurological disorders. The main underlying neuroprotective mechanisms in preventing and curing such disorders are the antioxidant, anti-inflammatory, anti-apoptotic, pro-neurotrophic and pro-estrogenic nature of the bioactive molecules. Conclusion: This review provides a lucid summary of the well-studied neuroprotective effects of Silymarin, its underlying molecular mechanisms and current limitations for its usage during neurological disorders. Finally, we have suggested a future course of action for developing it as a novel herbal drug for the treatment of brain diseases.

Biogenic green metal nano systems as efficient anti-cancer agents.

Metal/metal oxide nano systems (M-NSs) of tunable and manipulative properties are emerging suitable for cancer management via immunity development, early-stage diagnosis, nanotherapeutics, and targeted drug delivery systems. However, noticeable toxicity, off-targeted actions, lacking biocompatibility, and being expensive limit their acceptability. Moreover, involving high energy (top-down routes) and hazardous chemicals (bottom-up chemical routes) is altering human cycle. To manage such challenges, biomass (plants, microbes, animals) and green chemistry-based M-NSs due to scalability, affordability, are cellular, tissue, and organ acceptability are emerging as desired biogenic M-NSs for cancer management with enhanced features. The state-of-art and perspective of green metal/metal oxide nano systems (GM-NSs) as an efficient anti-cancer agent including, imaging, immunity building elements, site-specific drug delivery, and therapeutics developments are highlighted in this review critically. It is expected that this report will serve as guideline for design and develop high-performance GM-NSs for establishing them as next-generation anti-cancer agent capable to manage cancer in personalized manner.

Role of gut microbiota in tumorigenesis and antitumoral therapies: an updated review.

Gut microbiota plays a prominent role in regulation of host nutrientmetabolism, drug and xenobiotics metabolism, immunomodulation and defense against pathogens. It synthesizes numerous metabolites thatmaintain the homeostasis of host. Any disbalance in the normalmicrobiota of gut can lead to pathological conditions includinginflammation and tumorigenesis. In the past few decades, theimportance of gut microbiota and its implication in various diseases, including cancer has been a prime focus in the field of research. Itplays a dual role in tumorigenesis, where it can accelerate as wellas inhibit the process. Various evidences validate the effects of gutmicrobiota in development and progression of malignancies, wheremanipulation of gut microbiota by probiotics, prebiotics, dietarymodifications and faecal microbiota transfer play a significant role.In this review, we focus on the current understanding of theinterrelationship between gut microbiota, immune system and cancer,the mechanisms by which they play dual role in promotion andinhibition of tumorigenesis. We have also discussed the role ofcertain bacteria with probiotic characteristics which can be used tomodulate the outcome of the various anti-cancer therapies under theinfluence of the alteration in the composition of gut microbiota.Future research primarily focusing on the microbiota as a communitywhich affect and modulate the treatment for cancer would benoteworthy in the field of oncology. This necessitates acomprehensive knowledge of the roles of individual as well asconsortium of microbiota in relation to physiology and response ofthe host.

Putative role of mitochondria in SARS-CoV-2 mediated brain dysfunctions: a prospect.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic. Though the virus primarily damages the respiratory and cardiovascular systems after binding to the host angiotensin-converting enzyme 2 (ACE2) receptors, it has the potential to affect all major organ systems, including the human nervous system. There are multiple clinical reports of anosmia, dizziness, headache, nausea, ageusia, encephalitis, demyelination, neuropathy, memory loss, and neurological complications in SARS-CoV-2 infected individuals. Though the molecular mechanism of these brain dysfunctions during SARS-CoV-2 infection is elusive, the mitochondria seem to be an integral part of this pathogenesis. Emerging research findings suggest that the dysfunctional mitochondria and associated altered bioenergetics in the infected host cells lead to altered energy metabolism in the brain of Covid-19 patients. The interactome between viral proteins and mitochondrial proteins during Covid-19 pathogenesis also provides evidence for the involvement of mitochondria in SARS-CoV-2-induced brain dysfunctions. The present review discusses the possible role of mitochondria in disturbing the SARS-CoV-2 mediated brain functions, with the potential to use this information to prevent and treat these impairments.

Emerging MXene-Polymer Hybrid Nanocomposites for High-Performance Ammonia Sensing and Monitoring.

Ammonia (NH3) is a vital compound in diversified fields, including agriculture, automotive, chemical, food processing, hydrogen production and storage, and biomedical applications. Its extensive industrial use and emission have emerged hazardous to the ecosystem and have raised global public health concerns for monitoring NH3 emissions and implementing proper safety strategies. These facts created emergent demand for translational and sustainable approaches to design efficient, affordable, and high-performance compact NH3 sensors. Commercially available NH3 sensors possess three major bottlenecks: poor selectivity, low concentration detection, and room-temperature operation. State-of-the-art NH3 sensors are scaling up using advanced nano-systems possessing rapid, selective, efficient, and enhanced detection to overcome these challenges. MXene-polymer nanocomposites (MXP-NCs) are emerging as advanced nanomaterials of choice for NH3 sensing owing to their affordability, excellent conductivity, mechanical flexibility, scalable production, rich surface functionalities, and tunable morphology. The MXP-NCs have demonstrated high performance to develop next-generation intelligent NH3 sensors in agricultural, industrial, and biomedical applications. However, their excellent NH3-sensing features are not articulated in the form of a review. This comprehensive review summarizes state-of-the-art MXP-NCs fabrication techniques, optimization of desired properties, enhanced sensing characteristics, and applications to detect airborne NH3. Furthermore, an overview of challenges, possible solutions, and prospects associated with MXP-NCs is discussed.

An updated insight into the molecular pathogenesis, secondary complications and potential therapeutics of COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) is an unprecedented disease caused by highly pathogenic SARS-CoV-2 and characterized by extreme respiratory deterrence, pneumonia and immune damage. The phylogenetic analysis demonstrated the sequence similarity of SARS-CoV-2 with other SARS-like bat viruses. The primary source and intermediate host are not yet confirmed, although transmission from human to human is universally confirmed. The new SARS-CoV-2 virus reaches cells via ACE-2 and subsequently down-regulates ACE-2, leaving angiotensin II unbalanced in affected organs primarily in the lungs, heart, brain, and kidneys. As reported recently, numerous secondary complications i.e., neurological, nephrological, cardiovascular, gastrointestinal, immune, and hepatic complications, are associated with COVID-19 infection along with prominent respiratory disease including pneumonia. Extensive research work on recently discovered SARS-CoV-2 is in the pipeline to clarify pathogenic mechanisms, epidemiological features, and identify new drug targets that will lead to the development of successful strategies for prevention and treatment. There are currently no appropriate scientifically approved vaccines/drugs for COVID-19. Nonetheless, few broad-spectrum antiviral drugs, azithromycin were tested against COVID-19 in clinical trials, and finally, FDA approved emergency use of remdesivir in hospitalized COVID-19 patients. Additionally, administration of convalescent plasma obtained from recovered COVID-19 patients to infected COVID-19 patients reduces the viral burden via immunomodulation. This review analysis therefore concentrates primarily on recent discoveries related to COVID-19 pathogenesis along with a full description of the structure, genome, and secondary complication associated with SARS-CoV-2. Finally, a short and brief clinical update has been provided concerning the development of therapeutic medications and vaccines to counter COVID-19.

The temporal effect of hippocampal Arc in the working memory paradigm during novelty exploration.

Arc (activity-regulated cytoskeleton-associated protein) is one of the neuronal Immediate Early Genes (IEG), which is involved in the consolidation of memory and is an essential factor in the induction of Long-term Potentiation (LTP), Long-term Depression (LTD) and homeostatic synaptic plasticity. It has also been implicated in the increased familiarization of novel environments during reference memory paradigms. However, the Arc associated temporal effects in a working memory paradigm during novelty exploration are not well studied. Therefore, in the present study, we used spontaneous alternation behavior (SAB) test along with the expression analysis of Arc to study its temporal effects on the working memory paradigms. Using a modified SAB test, we found that the increase in the duration of exposure to a novel environment in the short time-scale (

Hippocampal Arc Induces Decay of Object Recognition Memory in Male Mice.

Activity-regulated cytoskeleton-associated (Arc) gene is one of the effector neuronal immediate early genes (IEG) that is rapidly upregulated after neuronal activation and is involved in synaptic long-term potentiation and depression. In recent years, it has been implicated in several cognitive disorders, viz. Angelman syndrome, Alzheimer's disease, fragile-X syndrome, etc. It undergoes quick transcription and highly regulated translation after exposure to a novel environment. Previous studies have shown that the presence of Arc mRNA primes mGluR-dependent long-term depression (LTD) in previously activated synapses upon re-exposure to the same environment. These studies suggest that the memory could be affected by the availability of Arc at the re-exposure time. Therefore, to confirm this, we investigated the changes in the temporal order memory and object recognition memory after the re-exposure to an environment in male mice. We studied the involvement of Arc in these changes by inhibiting Arc protein expression via stereotaxic infusions of Arc antisense oligodeoxynucleotides in the hippocampus of mice. We found that both temporal order and object recognition memories are dependent on the inter-familiarization phase interval. Strikingly, we also found that Arc accelerated the memory decay of an object when mice were re-exposed to the environment without that object.

Assessment of Cholinergic Properties of Ashwagandha Leaf-Extract in the Amnesic Mouse Brain.

BACKGROUND: In our earlier study, we have shown the memory enhancing and scopolamine-induced amnesia recovery properties of Ashwagandha leaf extract using behavioral paradigm and expression analysis of synaptic plasticity genes. PURPOSE: However, the exact mechanism through which Ashwagandha demonstrates these effects is still unknown. METHODS: In the present study, we hypothesized that the alcoholic extract of Ashwagandha leaves (i-Extract) possesses cholinergic properties, which in turn inhibit the anti-cholinergic nature of scopolamine. Therefore, the potential of i-Extract to recover from the scopolamine-induced cholinergic deficits was assessed by measuring acetylcholine (neurotransmitter) and Arc (synaptic activity-related gene) expression level in the mouse brain. RESULTS: The enzymatic activity of acetyl cholinesterase and choline acetyltransferase was assessed through colorimetric assays, and expression level of Arc protein was examined by Western blotting. Furthermore, mRNA level of these genes was examined by semi-quantitative reverse-transcriptase PCR. We observed that the treatment of i-Extract in scopolamine-induced amnesic mouse attenuates scopolamine-induced detrimental alterations in the cholinergic system. CONCLUSION: Thus, our study provided biochemical and molecular evidence of cholinergic properties of Ashwagandha leaf extract during brain disorders associated with cholinergic dysfunction.

Alcoholic Extract of Ashwagandha Leaves Protects Against Amnesia by Regulation of Arc Function.

Our earlier report on scopolamine-induced amnesia and its improvement by pre-treatment with i-Extract (alcoholic extract of Ashwagandha leaf) suggested that the i-Extract mediated nootropic effect may involve neuronal immediate early gene, Arc. With a hypothesis that the i-Extract induced expression of Arc protein may cause augmentation in Arc function, we examined the effect of i-extract on a major function of Arc protein, i.e. F-actin expansion, using Arc antisense oligodeoxynucleotides (ODN). Stereotaxic infusion of Arc antisense ODN in the CA1 region of hippocampus decreased the level of Arc protein as demonstrated by immunoblotting. However, this decrease was attenuated when treated with i-Extract prior to infusion of Arc antisense ODN. We noted a significant decrease in the polymerization of F-actin during scopolamine-induced amnesia as well as Arc antisense ODN infusion that was restored rather enhanced when pre-treated with i-Extract in both the cases. We also compared the corresponding changes between CA1 (the infusion site) and CA3 (neighbouring site of infusion) regions of hippocampus, and found more pronounced effects in CA1 than in the CA3 region. The extent of F-actin polymerization, as revealed by changes in the dendritic spine architecture through Golgi staining, showed that both scopolamine as well as Arc antisense ODN disrupted the spine density and mushroom-shaped morphology that was again regained if pre-treated with i-Extract. In conclusion, the findings reveal that the Arc helps in polymerization of F-actin and subsequent changes in the morphology of dendritic spines after pre-treatment with i-Extract in scopolamine-induced amnesic mice, suggesting an important role of Arc in scopolamine-induced amnesia and its recovery by i-Extract.

Bacopa monniera (CDRI-08) Upregulates the Expression of Neuronal and Glial Plasticity Markers in the Brain of Scopolamine Induced Amnesic Mice.

Preclinical studies on animal models have discerned the antiamnesic and memory-enhancing potential of Bacopa monniera (Brahmi) crude extract and standardized extracts. These studies primarily focus on behavioral consequences. However, lack of information on molecular underpinnings has limited the clinical trials of the potent herb in human subjects. In recent years, researchers highlight plasticity markers as molecular correlates of amnesia and being crucial to design therapeutic targets. In the present report, we have investigated the effect of a special extract of B. monniera (CDRI-08) on the expression of key neuronal (BDNF and Arc) and glial (GFAP) plasticity markers in the cerebrum of scopolamine induced amnesic mice. Pre- and postadministration of CDRI-08 ameliorated amnesic effect of scopolamine by decreasing acetyl cholinesterase activity and drastically upregulating the mRNA and protein expression of BDNF, Arc, and GFAP in mouse cerebrum. Interestingly, the plant extract per se elevated BDNF and Arc expression as compared to control but GFAP was unaltered. In conclusion, our findings provide the first molecular evidence for antiamnesic potential of CDRI-08 via enhancement of both neuronal and glial plasticity markers. Further investigations on detailed molecular pathways would encourage therapeutic application of the extract in memory disorders.

Involvement of hippocampal Arc in amnesia and its recovery by alcoholic extract of Ashwagandha leaves.

Arc (Activity-regulated cytoskeletal-associated protein) is a member of the immediate-early gene (IEG) family protein. Because of its critical role in learning and memory, it is widely considered to be an important protein in synaptic plasticity and related neurobiological functions. Alcoholic extract of Ashwagandha leaves (i-Extract) was recently shown to have preventive and therapeutic potential for scopolamine-induced amnesia and glutamate-induced excitotoxicity. In the present study, we investigated the involvement of Arc in scopolamine-induced amnesia and its recovery by i-Extract with particular focus to the changes in Arc expression in the hippocampus and cerebral cortex of mice. Morris water maze test showed that spatial learning and memory of mice were drastically reduced by scopolamine administration but improved with i-Extract treatment as compared to control and scopolamine-challenged mice. Molecular analysis revealed a remarkable decline in Arc expression in both hippocampus and cerebral cortex of amnesic mice, which was recovered after i-Extract treatment. Interestingly, Arc expression showed better recovery in the hippocampus than the cerebral cortex and the pre-treatment with i-Extract was more effective than the post-treatment. These findings suggest that Arc may be involved in i-Extract mediated recovery from amnesia.