Microbial oases in the ice: A state-of-the-art review on cryoconite holes as diversity hotspots and their scientific connotations.

Cryoconite holes, small meltwater pools on the surface of glaciers and ice sheets, represent extremely cold ecosystems teeming with diverse microbial life. Cryoconite holes exhibit greater susceptibility to the impacts of climate change, underlining the imperative nature of investigating microbial communities as an essential module of polar and alpine ecosystem monitoring efforts. Microbes in cryoconite holes play a critical role in nutrient cycling and can produce bioactive compounds, holding promise for industrial and pharmaceutical innovation. Understanding microbial diversity in these delicate ecosystems is essential for effective conservation strategies. Therefore, this review discusses the microbial diversity in these extreme environments, aiming to unveil the complexity of their microbial communities. The current study envisages that cryoconite holes as distinctive ecosystems encompass a multitude of taxonomically diverse and functionally adaptable microorganisms that exhibit a rich microbial diversity and possess intricate ecological functions. By investigating microbial diversity and ecological functions of cryoconite holes, this study aims to contribute valuable insights into the broader field of environmental microbiology and enhance further understanding of these ecosystems. This review seeks to provide a holistic overview regarding the formation, evolution, characterization, and molecular adaptations of cryoconite holes. Furthermore, future research directions and challenges underlining the need for long-term monitoring, and ethical considerations in preserving these pristine environments are also provided. Addressing these challenges and resolutely pursuing future research directions promises to enrich our comprehension of microbial diversity within cryoconite holes, revealing the broader ecological and biogeochemical implications. The inferences derived from the present study will provide researchers, ecologists, and policymakers with a profound understanding of the significance and utility of cryoconite holes in unveiling the microbial diversity and its potential applications.

Unraveling the potential of environmental DNA for deciphering recent advances in plant-animal interactions: a systematic review.

MAIN CONCLUSION: Environmental DNA-based monitoring provides critical insights for enhancing our understanding of plant-animal interactions in the context of worldwide biodiversity decrease for developing a global framework for effective plant biodiversity conservation. To understand the ecology and evolutionary patterns of plant-animal interactions (PAI) and their pivotal roles in ecosystem functioning advances in molecular ecology tools such as Environmental DNA (eDNA) provide unprecedented research avenues. These methods being non-destructive in comparison to traditional biodiversity monitoring methods, enhance the discernment of ecosystem health, integrity, and complex interactions. This review intends to offer a systematic and critical appraisal of the prospective of eDNA for investigating PAI. The review thoroughly discusses and analyzes the recent reports (2015-2022) employing preferred reporting items for systematic reviews and meta-analyses (PRISMA) to outline the recent progression in eDNA approaches for elucidating PAI. The current review envisages that eDNA has a significant potential to monitor both plants and associated cohort of prospective pollinators (avian species and flowering plants, bees and plants, arthropods and plants, bats and plants, etc.). Furthermore, a brief description of the factors that influence the utility and interpretation of PAI eDNA is also presented. The review establishes that factors such as biotic and abiotic, primer selection and taxonomic resolution, and indeterminate spatio-temporal scales impact the availability and longevity of eDNA. The study also identified the limitations that influence PAI detection and suggested possible solutions for better execution of these molecular approaches. Overcoming these research caveats will augment the assortment of PAI analysis through eDNA that could be vital for ecosystem health and integrity. This review forms a critical guide and offers prominent insights for ecologists, environmental managers and researchers to assess and evaluate plant-animal interaction through environmental DNA.

Synthetic and Natural Bioactive Molecules in Balancing the Crosstalk among Common Signaling Pathways in Alzheimer's Disease: Understanding the Neurotoxic Mechanisms for Therapeutic Intervention.

The structure and function of the brain greatly rely on different signaling pathways. The wide variety of biological processes, including neurogenesis, axonal remodeling, the development and maintenance of pre- and postsynaptic terminals, and excitatory synaptic transmission, depends on combined actions of these molecular pathways. From that point of view, it is important to investigate signaling pathways and their crosstalk in order to better understand the formation of toxic proteins during neurodegeneration. With recent discoveries, it is established that the modulation of several pathological events in Alzheimer's disease (AD) due to the mammalian target of rapamycin (mTOR), Wnt signaling, 5'-adenosine monophosphate activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), and sirtuin 1 (Sirt1, silent mating-type information regulator 2 homologue 1) are central to the key findings. These include decreased amyloid formation and inflammation, mitochondrial dynamics control, and enhanced neural stability. This review intends to emphasize the importance of these signaling pathways, which collectively determine the fate of neurons in AD in several ways. This review will also focus on the role of novel synthetic and natural bioactive molecules in balancing the intricate crosstalk among different pathways in order to prolong the longevity of AD patients.

Clinical Biomarkers and Novel Drug Targets to Cut Gordian Knots of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD), the primary cause of dementia, escalating worldwide, has no proper diagnosis or effective treatment. Neuronal cell death and impairment of cognitive abilities, possibly triggered by several brain mechanisms, are the most significant characteristic of this disorder. METHODS: A multitude of pharmacological targets have been identified for potential drug design against AD. Although many advances in treatment strategies have been made to correct various abnormalities, these often exhibit limited clinical significance because this disease aggressively progresses into different regions of the brain, causing severe deterioration. RESULTS: These biomarkers can be game-changers for early detection and timely monitoring of such disorders. CONCLUSION: This review covers clinically significant biomarkers of AD for precise and early monitoring of risk factors and stages of this disease, the potential site of action and novel targets for drugs, and pharmacological approaches to clinical management.

Dysfunction of ABC Transporters at the Surface of BBB: Potential Implications in Intractable Epilepsy and Applications of Nanotechnology Enabled Drug Delivery.

Epilepsy is a chronic neurological disorder affecting 70 million people globally. One of the fascinating attributes of brain microvasculature is the (BBB), which controls a chain of distinct features that securely regulate the molecules, ions, and cells movement between the blood and the parenchyma. The barrier's integrity is of paramount importance and essential for maintaining brain homeostasis, as it offers both physical and chemical barriers to counter pathogens and xenobiotics. Dysfunction of various transporters in the (BBB), mainly ATP binding cassette (ABC), is considered to play a vital role in hampering the availability of antiepileptic drugs into the brain. ABC (ATP-binding cassette) transporters constitute a most diverse protein superfamily, which plays an essential part in various biological processes, including cell homeostasis, cell signaling, uptake of nutrients, and drug metabolism. Moreover, it plays a crucial role in neuroprotection by out-flowing various internal and external toxic substances from the interior of a cell, thus decreasing their buildup inside the cell. In humans, forty-eight ABC transporters have been acknowledged and categorized into subfamilies A to G based on their phylogenetic analysis. ABC subfamilies B, C, and G, impart a vital role at the BBB in guarding the brain against the entrance of various xenobiotic and their buildup. The illnesses of the central nervous system have received a lot of attention lately Owing to the existence of the BBB, the penetration effectiveness of most CNS medicines into the brain parenchyma is very limited (BBB). In the development of neurological therapies, BBB crossing for medication delivery to the CNS continues to be a major barrier. Nanomaterials with BBB cross ability have indeed been extensively developed for the treatment of CNS diseases due to their advantageous properties. This review will focus on multiple possible factors like inflammation, oxidative stress, uncontrolled recurrent seizures, and genetic polymorphisms that result in the deregulation of ABC transporters in epilepsy and nanotechnology-enabled delivery across BBB in epilepsy.

A Comprehensive Review on Journey of Pyrrole Scaffold Against Multiple Therapeutic Targets.

Heterocyclic compounds are that type of substances that are deeply intertwined with biological processes. Heterocycles are found in about 90% of commercially available medicines. In medicinal chemistry, finding new synthetic molecules with drug-like characteristics is a regular problem, which triggered the development of pharmacological molecules, the majority of which are based on N-heterocyclic motifs. Among the heterocycles, the pyrrole scaffold is the most commonly found heterocycle in both natural and synthetic bioactive compounds. Pyrrole has a fivemembered heterocyclic ring with a plethora of pharmacophores, resulting in a library of different lead compounds. Pyrrole derivatives are physiologically active heterocyclic compounds that can be used as scaffolds for antibacterial, antiviral, anticancer, antitubercular, anti-inflammatory, and as enzyme inhibitors. On account of their extensive pharmacological profile, pyrrole and its various synthetic derivatives have drawn much attention from researchers to explore it for the benefit of humankind. This review presents an overview of recent developments in the pyrrole derivatives against multiple therapeutic targets.

Berberine in the Treatment of Neurodegenerative Diseases and Nanotechnology Enabled Targeted Delivery.

BACKGROUND: Berberine (BBR), an alkaloidal compound found in many plants, is widely used for hundreds of years in the traditional system of Chinese medicine. OBJECTIVE/AIM: The present review is aimed to summarize the potential of Berberine in the amelioration of various neurological disorders. METHODS: The collection of data for the compilation of this review work was searched in PubMed Scopus, Google Scholar, and Science Direct. Of late, researchers are more focused on its beneficial role in neurodegenerative diseases. RESULTS: BBR has proven its protective role in numerous neurotoxicity models including, oxygen-glucose deprivation, mercury-induced, neurodegenerative model by ibotenic acid, and hypoxia caused by COCl2. BBR treatment averts the generation of reactive oxygen species in the oxygen-glucose deprivation model. Further, it subdues cytochrome c along with the divulge of apoptosis-inducing factors that indicate its beneficial action in the management of stroke. BBR diminished hydrogen peroxide-induced neuronal damage by enhancing the PI3k / Akt / Nrf-2 based pathway and showed a preventive impact on neurites of SH-SY5Y cells by averting the formation of ROS and inhibiting apoptosis. The impact of BBR on neurological disorder using a transgenic AD type mouse strain (TgCRND8) showed a reduction in the piling up of amyloid-ß plaque. In mice, administration of BBR in the dose range of 5-10m/kg has been reported to raise the levels of serotonin (47%), dopamine (31%), and norepinephrine (29%) in CNS to allay depression. CONCLUSION: The present review is aimed to summarize the potential of Berberine in the amelioration of various neurological disorders.

Novel Drug Delivery System for Curcumin: Implementation to Improve Therapeutic Efficacy against Neurological Disorders.

BACKGROUND: Curcumin, a hydrophobic polyphenolic compound present in Curcuma longa Linn. (Turmeric), has been used to improve various neurodegenerative conditions, including Amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Prion disease, stroke, anxiety, depression, and ageing. However, the Blood-Brain Barrier (BBB) impedes the delivery of curcumin to the brain, limiting its therapeutic potential. OBJECTIVE/AIM: This review summarises the recent advances towards the therapeutic efficacy of curcumin along with various novel strategies to overcome its poor bioavailability across the bloodbrain barrier. METHODS: The data for the compilation of this review work were searched in PubMed Scopus, Google Scholar, and Science Direct. RESULTS: Various approaches have been opted to expedite the delivery of curcumin across the blood-brain barrier, including liposomes, micelles, polymeric nanoparticles, exosomes, dualtargeting nanoparticles, etc. Conclusion: The review also summarises the numerous toxicological studies and the role of curcumin in CNS disorders.

Plant-Derived Natural Compounds for the Treatment of Amyotrophic Lateral Sclerosis: An Update.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease (MND) that typically causes death within 3-5 years after diagnosis. Regardless of the substantial scientific knowledge accrued more than a century ago, truly effective therapeutic strategies remain distant. Various conventional drugs are being used but are having several adverse effects. OBJECTIVE/AIM: The current study aims to thoroughly review plant-derived compounds with welldefined ALS activities and their structure-activity relationships. Moreover, the review also focuses on complex genetics, clinical trials, and the use of natural products that might decrypt the future and novel therapeutics in ALS. METHODS: The collection of data for the compilation of this review work was searched in PubMed Scopus, Google Scholar, and Science Direct. RESULTS: Results showed that phytochemicals like-Ginkgolides, Protopanaxatriol, Genistein, epigallocatechingallate, resveratrol, cassoside, and others possess Amyotrophic lateral sclerosis (ALS) activity by various mechanisms Conclusion: These plant-derived compounds may be considered as supplements for conventional (ALS). Moreover, further preclinical and clinical studies are required to understand the structureactivity relationships, metabolism, absorption, and mechanisms of plant-derived natural agents.

Bioactive Heterocyclic Compounds as Potential Therapeutics in the Treatment of Gliomas: A Review.

Cancer is one of the most alarming diseases, with an estimation of 9.6 million deaths in 2018. Glioma occurs in glial cells surrounding nerve cells. The majority of the patients with gliomas have a terminal prognosis, and the ailment has significant sway on patients and their families, be it physical, psychological, or economic wellbeing. As Glioma exhibits, both intra and inter tumour heterogeneity with multidrug resistance and current therapies are ineffective. So the development of safer anti gliomas agents is the need of hour. Bioactive heterocyclic compounds, eithernatural or synthetic, are of potential interest since they have been active against different targets with a wide range of biological activities, including anticancer activities. In addition, they can cross the biological barriers and thus interfere with various signalling pathways to induce cancer cell death. All these advantages make bioactive natural compounds prospective candidates in the management of glioma. In this review, we assessed various bioactive heterocyclic compounds, such as jaceosidin, hispudlin, luteolin, silibinin, cannabidiol, tetrahydrocannabinol, didemnin B, thymoquinone, paclitaxel, doxorubicin, and cucurbitacins for their potential anti-glioma activity. Also, different kinds of chemical reactions to obtain various heterocyclic derivatives, e.g. indole, indazole, benzimidazole, benzoquinone, quinoline, quinazoline, pyrimidine, and triazine, are listed.

Depression: An Insight into Heterocyclic and Cyclic Hydrocarbon Compounds Inspired from Natural Sources.

Depression, a well-known mental disorder, has global prevalence, affecting nearly 17% of the population. Due to various limitations of the currently available drugs, people have been adopting traditional herbal medicines to alleviate the symptoms of depression. It is notable to mention that natural products, their derivatives, and their analogs are the main sources for new drug candidates of depression. The mechanisms include interplay with γ-aminobutyric acid (GABA) receptors, serotonergic, dopaminergic noradrenergic systems, and elevation of BDNF levels. The focus of this article is to review the role of signalling molecules in depression and highlight the use of plant-derived natural compounds to counter CNS depression.

Natural Anti-inflammatory Compounds as Drug Candidates in Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative brain disorder characterized by memory impairment, dementia, and oxidative stress in elderly people. Currently, only a few drugs are available in the market with various adverse effects. Therefore, to develop new drugs with protective action against the disease, research is turning to the identification of plant products as a remedy. Natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Phytochemicals, including Curcumin, Resveratrol, Quercetin, Huperzine-A, Rosmarinic acid, genistein, obovatol, and Oxyresvertarol, were reported molecules for the treatment of AD. Several alkaloids, such as galantamine, oridonin, glaucocalyxin B, tetrandrine, berberine and anatabine, have been shown anti-inflammatory effects in AD models in vitro as well as in-vivo. In conclusion, natural products from plants represent interesting candidates for the treatment of AD. This review highlights the potential of specific compounds from natural products along with their synthetic derivatives to counteract AD in the CNS.