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Nardostachys jatamansi has long been used to prepare Medhya Rasayana in traditional Indian Ayurveda medicine to treat neurological disorders and enhance memory. Jatamansinol from the N. jatamansi against Alzheimer's disease (AD) showed that it could be a multitargeted drug against AD. Drosophila is an ideal model organism for studying a progressive age-related neurodegenerative disease such as AD since its neuronal organizations and functioning are highly similar to that of humans. The current study investigates the neuroprotective properties of jatamansinol against Tau-induced neurotoxicity in the AD Drosophila model. Results indicate jatamansinol is not an antifeedant for larva and adult Drosophila. Lifespan, locomotor activity, learning and memory, Tau protein expression level, eye degeneration, oxidative stress level, and cholinesterase activities were analyzed in 10, 20, and 30-day-old control (wild type), and tauopathy flies reared on jatamansinol supplemented food or regular food without jatamansinol supplementation. Jatamansinol treatment significantly extends the lifespan, improves locomotor activity, enhances learning and memory, and reduces Tau protein levels in tauopathy flies. It boosts the antioxidant enzyme activities, prevents Tau-induced oxidative stress, ameliorates eye degeneration, and inhibits cholinesterase activities in Tau-induced AD model. This study provides the first evidence that jatamansinol protects against Tau's neurotoxic effect in the AD Drosophila model, and it can be a potential therapeutic drug candidate for AD.

Alzheimer's disease (AD) is a multifactorial progressive and irreversible neurodegenerative disorder characterized by severe memory impairment and cognitive disability in the middle and old-aged human population. There are no proven drugs for AD treatment and prevention. In Ayurveda, medhya plants are used to prepare Rasayana, and its consumption improves memory and cognition. Nardostachys jatamansi (D.Don) DC is a medhya plant used in traditional medicine to treat neurological disorders, and its unique pyranocoumarins can be a potential drug candidate for AD. Given its traditional claims, this study aims to find the multi-target potential efficacy of the ligands (drug molecules) against the AD from N. jatamansi pyranocoumarins using computational drug discovery techniques. Drug likeliness analysis confirms that pyranocoumarins of N. jatamansi, such as seselin, jatamansinol, jatamansine, jatamansinone, and dihydrojatamansin are probable drug candidates for AD. Molecular docking, molecular dynamic simulations, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis confirm that dihydrojatamansin inhibits acetylcholinesterase (AChE), and jatamansinol inhibits butyrylcholinesterase (BuChE), glycogen synthase kinase 3β (GSK3β), and kelch-like ECH-associating protein 1 (Keap1) AD therapeutic targets. Therefore, this study provides potential multi-target inhibitors that would further validate experimental studies, leading to new treatments for AD.Communicated by Ramaswamy H. Sarma.

Tigerinins are antimicrobial peptides (AMPs) derived from the skin secretions of the Indian bullfrog Hoplobatrachus tigerinus.Tigerinin-1 (FCTMIPIPRCY-Am) peptide was synthesized by solid-phase Fmoc chemistry and investigated its antitumor activities.Tigerinin-1 was cytotoxic to human cancer cells. It causes necrosis by damaging the cell membrane and loss of lysosome integrity. Tigerinin-1triggers the expression of necroptosis pathway proteins. It generates reactive oxygen species (ROS) and induces oxidative stress-mediated genotoxicity. Tigerinin-1 inhibits cancer cell proliferation, reduces neovascularization, and down-regulates the vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and fibroblast growth factor (FGF) genes.Tigerinin-1 exhibited its potent antitumor properties in this study.Tigerinin-1 can be beneficial for developing novel therapeutics for cancer.

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterised by three main behavioural symptoms: abnormal social interaction, verbal and non-verbal communication impairments, and repetitive and restricted activities or interests. Even though the exact aetiology of ASD remains unknown, studies have shown a link between genetics and environmental pollutants. Heavy metal lead (Pb), the environmental pollutant, is associated with ASD. Pb may also exhibit sex-specific ASD behaviour, as has been demonstrated in the global human populations. Drosophila melanogaster as a model has been used in the present study to understand the involvement of Pb-induced oxidative stress in developing ASD behaviour. The larval feeding technique has been employed to administer different Pb concentrations (0.2–0.8 mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) antioxidants overexpressed or knockdown flies. Adult Drosophila (5-day old) were used for Pb content, biochemical, and behavioural analysis.Pb accumulated in the Drosophila brain induces oxidative stress and exhibited a human autistic-like behaviour such as reduced climbing, increased grooming, increased social spacing, and decreased learning and memory in a sex-specific manner.Pb-induced autistic-like behaviour was intensified in Sod or Cat-knockdown flies, whereas Sod or Cat-overexpressed flies overcome that behavioural alterations. These results unequivocally proved that Pb-induced oxidative stress causes ASD behaviour of humans in Drosophila. Thus, Drosophila is used as a model organism to analyse ASD-like human behaviour and underlines the importance of using antioxidant therapy in alleviating ASD symptoms in children.

Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus called SARS-CoV-2. It has affected over 200 countries and inflicted significant mortalities as well as disrupted the normal social and economic processes. In the absence of an established effective vaccination, the cornerstone of COVID-19 management largely depends on containment and mitigation strategies. However, it is increasingly felt that digital health can be widely used to facilitate COVID-19 pandemic management effectively, which is otherwise difficult to attain manually. Many countries depended on health technology to contain the impact of the virus. However, Singapore, a small country in the South-East Asian region demonstrated exemplary pandemic preparedness skills coupled with adoption of digital health technology to attain remarkable success in containing the virus.

Biocatalysis has demonstrated to be more sustainable, and the most economical, efficient, and eco-friendly process in the production of active pharmaceutical intermediates (APIs) and pharmaceuticals. Recent developments in biocatalytic reactions are driven by the advances in biochemistry, recombinant DNA technology, enzyme engineering, bioinformatics, random and site-directed mutagenesis, enzyme-directed evolution, high-throughput enzyme screening and analysis, fermentation, and robotic-artificial intelligence technologies. Biocatalysis is one of the most promising technologies, but it needs more innovation for the sustainable synthesis of advanced novel active pharmaceuticals and APIs for the future pharmaceutical. This chapter highlights the history of biocatalysis and recent developments in the production of advanced therapeutic drugs in the pharmaceutical industry.

A pandemic is a global epidemic. Infectious diseases have killed more humans than others in history. The history of global pandemic diseases has shaped human history and has taught us how to manage current and future infectious diseases. Knowledge of past pandemics is ignored and not followed, leading to repeated failure to prevent emerging infectious diseases. Pandemics’ history has highlighted the persistent socioeconomic classes, xenophobia, and pervasive fear of the invisible enemy pathogen. Animals are the reservoir of pandemic disease pathogens; they also act as vectors. Factors such as urbanization, habitat destruction, habitat loss, and trade of high-risk live wild animals and their meat, and unsustainable food systems have been responsible for disease outbreaks. During ancient times, the best containment measures are the same weapons that are used in the 21st century to fight the new global attack. From the prehistoric to 21st-century pandemic, we have not understood many fundamental aspects of emerging infectious diseases. We need to understand the origin and evolution of the novel human emerging infectious diseases. It is critical for tracking pathogenicity, designing useful interventions, developing drug and vaccine, and innovating the technology to produce the necessary medicines and vaccines in bulk quantity rapidly.

Coronaviruses (CoVs) are pathogens that threaten human health. Several CoVs are maintained in nature, recombine, mutate, evolve, and emerge as novel CoVs to cause new zoonotic diseases. CoVs infection displays immense interindividual clinical variability, varying from asymptomatic to severe. Risk factors, such as older age, underlying health conditions, and the human genome could address the disease’s variable symptoms. The possible association between disease severity and DNA polymorphisms in the virus-host factors presents a unique opportunity to reveal human genetic determinants in infection and disease susceptibility. This chapter emphasizes the history, taxonomy, naming, genetic diversity of CoVs, the genome of CoVs, and potential genes for diseases’ pathogenesis. This information can help to prepare countermeasures against future spillover and pathogenic infections in humans with novel CoVs.

The widespread use of lead (Pb) has caused global contamination, inevitable human exposure, and public health problems. Pb neurotoxicity has been linked to various human diseases, but its associated mechanism causing neurotoxicity is unknown. Drosophila melanogaster as a model organism has been used to study the mechanism involved in Pb-caused neurotoxicity and the potential role of antioxidants in ameliorating its harmful effects. The larval feeding technique was adopted to administer different concentrations of Pb (0.2-0.8 mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) overexpressing, and Sod or Cat knockdown flies to analyse Pb load, oxidative stress components, DNA damage, apoptosis and vacuolation in the brain. The results revealed that Pb accumulation in the Drosophila brain induces oxidative stress by generating reactive oxygen species (ROS) and lipid peroxidation (LPO), depleting antioxidant enzymes. Molecular docking studies have evidenced it. Pb directly binds to antioxidants and major grooves of DNA, leading to DNA damage. Increased DNA damage, apoptosis, vacuolation in brains of Pb-treated ORR, Sod, or Cat knockdown flies; and on the contrary, reduced oxidative DNA damage, apoptosis, and vacuolation in brains of Pb treated Sod or Cat overexpressed flies put forward that oxidative stress is the mechanism in Pb caused neurotoxicity.

Background Malathion is the most widely used organophosphate pesticide in agriculture. Increasing cancer incidence in agricultural workers and their children links to the exposure of malathion. Identification of genes involved in the process of carcinogenesis is essential for exploring the role of malathion. The alteration in gene expression by malathion in human lymphocytes has not been explored yet, although hematological malignancies are rampant in humans. Objective This study investigates the malathion induced expression of cancer associated genes in human lymphocytes. Methods Human lymphocyte viability and colony-forming ability were analyzed in malathion treated and control groups. Gene expression profile in control and malathion treated human lymphocytes were performed using a microarray platform. The genes which have significant functions and those involved in different pathways were analyzed using the DAVID database. Differential gene expression upon malathion exposure was validated by quantitative real-time (qRT)-PCR. Results Malathion caused a concentration-dependent reduction in human lymphocyte viability. At low concentration (50 μg/mL) of malathion treatment, human lymphocytes were viable indicating that low concentration of malathion is not cytotoxic and induces the colony formation. Total of 659 genes (15%) were up regulated and 3729 genes (85%) were down regulated in malathion treated human lymphocytes. About 57 cancer associated genes related to the growth and differentiation of B and T cells, immunoglobulin production, haematopoiesis, tumor suppression, oncogenes and signal transduction pathways like MAPK and RAS were induced by malathion. Conclusion This study evidences the carcinogenic nature of malathion. Low concentration of this pesticide is not cytotoxic and induces differentially regulated genes in human lymphocytes, which are involved in the initiation, progression, and pathogenesis of cancer.

Purpose: To understand the role of hyperthermia in adaptive response, Ethyl methanesulfonate (EMS) an anticarcinogenic agent, adapted meiotic cells of Poecilocerus pictus was used. Materials and methods: Based on the pilot toxicity study, the effective higher temperatures of 40 °C and 45 °C for 15 or 30 min were chosen. P. pictus were treated with conditioning (L) or challenging (H) doses of EMS and 2 h time lag (TL) between these doses (L-2 h-H) was employed. Different treatment schedules were used to analyze the influence of hyperthermia on EMS induced adaptive response namely (i) pre treatment; (ii) inter treatment; (iii) post treatment and (iv) cross adaptation. After each treatment schedule, animals were sacrificed at 12, 24, 36 and 48 h recovery times, testes were processed for meiotic chromosome preparations and anomalies were analyzed. Results: The frequencies of anomalies induced by both conditioning and challenging doses of EMS were significantly higher (p

To understand the role of hyperthermia (HT) in adaptive response, methyl methanesulfonate (MMS) adapted meiotic cells of Poecilocerus pictus were used. Poecilocerus pictus were treated with conditioning (L) or challenging (H) dose of MMS and 2-h time lag (TL) between these doses (L-2h-H) (combined) was employed. Different treatment schedules were used to analyse the influence of HT on MMS-induced adaptive response namely pre; inter; post-treatment and cross-adaptation. After each treatment schedules, chromosomal anomalies were analysed. The frequencies of chromosomal anomalies induced by conditioning and challenging doses of MMS were significantly higher (P < 0.0001) compared to that of the control or HT groups. The combined treatments resulted in significant reduction of chromosomal anomalies compared to additive effect of MMS (P < 0.0001). The pre, inter, post and cross-adaptation treatments with HT reduced the frequencies of chromosomal anomalies compared to the challenge and combined treatments with MMS. There is a protection against MMS-induced chromosomal anomalies by HT in in vivo P.pictus. This is the first report to demonstrate that HT enhances the MMS-induced adaptive response in in vivo meiotic cells.

Despite mounting concerns about amphibian population declines, information on impact of pesticides on physiological changes is meager. The present study deals the influence of an organophosphate pesticide—malathion on the lipid metabolism of Limnonectus limnocharis under laboratory conditions. Changes in the lipid metabolism were analyzed in the liver, muscle, ovary, and testis of frogs exposed to lethal (10.67 mg L−1 for 1, 2, 3, and 4 days) and sub-lethal (2.13 mg L−1 for 1, 5, 10, 15, 20, and 25 days) concentrations of malathion. Upon lethal concentration treatment, against the increase of fatty acids, glycerol, and lipase activities in all tested tissues, there was decrease in the total lipids content over different durations. On the other hand, exposure to sub-lethal concentration, the amount of total lipids content, free fatty acids, glycerol and lipase activity increased. Changes in the lipid metabolism due to lethal concentration of malathion exposure could depict the negative impact on the reproductive success, which would result in decline of amphibian population.

The present paper reports the abnormalities recorded among four species of frogs: Limnonectus limnocharis, L. keralensis, L. brevipalmata, and Tomopterna (Spherotheca) rufescens inhabiting forest, water bodies, agriculture (paddy) fields and coffee plantations. The survey and sampling was made over a period of three years in early post monsoon (October) of 2001, 2002 and 2003. Of 6,303 frogs encountered 229 were abnormal (3.63%). Among the four types of habitat, coffee plantation has a high incidence of abnormality (4.64%), followed by agriculture field (paddy) (3.98%) and water bodies (3.92%), while no abnormal frogs were recorded from surveyed forest sites. Among the four species, maximum abnormality was recorded in L. brevipalmata (8.92%) followed by T. rufescens (6.12%), L. limnocharis and L. keralensis (3.26% each). Excepting the forest, in all other sampling areas, large amount of chemical fertilizers and pesticides are being used. Therefore, we suspect chemical contamination as a factor causing the abnormality in this region, but this needs confirmation.

The effects of short-term exposure (28 days) of free-feeding Limnonectus limnocharis (Indian cricket frog) tadpoles to field concentrations of malathion were investigated. This frog species is a major biotic component of the agroecosystems of the Western Ghats (13 degrees 18', 75 degrees 25' and 13 degrees 22', 75 degrees 28'), where malathion (diethyl [(dimethoxy phosphino thioyl] butanediote), an organophosphate pesticide, is being used extensively. Although malathion is known to cause nonreversible acetylcholine inhibition and diminishes activity, growth and development in amphibian tadpoles, such data on Indian amphibian species are lacking. In the present study, increments in the following were used to assess such an impact: tadpole growth; increase in total length, body length, tail length, and body weight; and food consumption. The different concentrations of malathion employed were 500, 1000, 1500, 2000, and 3000 mug L(-1). Malathion exposure produced significant effects on all measured parameters. Tadpole survival decreased from 20 to 6 tadpoles, with an increase in concentration followed by a decrease in growth. Food consumption of surviving tadpoles also decreased (0.067 mg.g(-1).d(-1) to 0.0075 mg.g(-1).d(-1)) with increased malathion. Decreased food consumption, growth, and development of L. limnocharis tadpoles with an increase of malathion concentration (within field concentration range) over temporal scale reveal the possible threat to this species in the agroecosystems of the Western Ghats.

The unprecedented decline in amphibian populations is reported to be caused by several factors, including environmental contaminants of agriculture pesticides. In natural conditions, application of pesticides or other chemicals to crop fields coincides with breeding seasons of many amphibian species inhabiting the agro-ecosystem, resulting in exposure of eggs, tadpoles, and metamorphs. Glycoconjugates are key molecules in cell adhesion and signaling in higher invertebrates and vertebrates. In amphibians, sialic acid of free glycoconjugates in egg jelly facilitates the adherence of spermatozoa to the egg surface. Considering the possibility of exposure of amphibian eggs to pesticides in agro-ecosystems, the present study was undertaken to determine the effect of different concentrations of malathion and methyl parathion pesticides on the eggs of Fejervarya limnocharis (Indian Cricket frog). Following thiobarbituric acid and fertilization assay, changes in sialic acid content and egg hatchability were measured in eggs exposed to the two pesticides, respectively, for different time intervals. Sialic acid content and hatchability were reduced significantly in eggs treated with pesticides. The time of exposure has also an influence on the amount of sialic acid content and egg hatchability. The results demonstrate that exposure to pesticides alters sialic acid content in jelly coat of amphibian eggs leading to inhibition of sperm penetration.