Therapeutic potential of nicorandil beyond anti-anginal drug: A review on current and future perspectives.

Nicorandil (NIC) is a well-known anti-anginal agent, which has been recommended as one of the second-line treatments for chronic stable angina as justified by the European guidelines. It shows an efficacy equivalent to that of classic anti-anginal agents. NIC has also been used clinically in various cardiovascular diseases such as variant or unstable angina and reperfusion-induced damage following coronary angioplasty or thrombolysis. Different mechanisms have been involved in the protective effects of nicorandil in various diseases, including opening of adenosine triphosphate-sensitive potassium (KATP) channel and donation of nitric oxide (NO). In recent years, NIC has been found to show numerous pharmacological activities such as neuroprotective, nephroprotective, hepatoprotective, cardioprotective, and testicular protective effects, among other beneficial effects on the body. The present review dwells on the pharmacological potentials of NIC beyond its anti-anginal action.

Interplay between α-synuclein and parkin genes: Insights of Parkinson's disease.

Parkinson's disease (PD) is a complex and debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The pathogenesis of PD is intimately linked to the roles of two key molecular players, α-synuclein (α-syn) and Parkin. Understanding the intricate interplay between α-syn and Parkin is essential for unravelling the molecular underpinnings of PD. Their roles in synaptic function and protein quality control underscore their significance in neuronal health. Dysregulation of these processes, as seen in PD, highlights the potential for targeted therapeutic strategies aimed at restoring normal protein homeostasis and mitigating neurodegeneration. Investigating the connections between α-syn, Parkin, and various pathological mechanisms provides insights into the complex web of factors contributing to PD pathogenesis and offers hope for the development of more effective treatments for this devastating neurological disorder. The present compilation provides an overview of their structures, regional and cellular locations, associations, physiological functions, and pathological roles in the context of PD.

Cross Talks between CNS and CVS Diseases: An Alliance to Annihilate.

Cardiovascular and neurological diseases cause substantial morbidity and mortality globally. Moreover, cardiovascular diseases are the leading cause of death globally. About 17.9 million people are affected by cardiovascular diseases and 6.8 million people die every year due to neurological diseases. The common neurologic manifestations of cardiovascular illness include stroke syndrome which is responsible for unconsciousness and several other morbidities significantly diminished the quality of life of patients. Therefore, it is prudent need to explore the mechanistic and molecular connection between cardiovascular disorders and neurological disorders. The present review emphasizes the association between cardiovascular and neurological diseases specifically Parkinson's disease, Alzheimer's disease, and Huntington's disease.

Potential Antidiabetic Activity of ß-sitosterol from Zingiber roseum Rosc. via Modulation of Peroxisome Proliferator-activated Receptor Gamma (PPARγ).

AIM: To evaluate the antidiabetic potential of ß-sitosterol from Zingiber roseum. BACKGROUND: Diabetes mellitus is a cluster of metabolic disorders, and 90% of diabetic patients are affected with Type II diabetes (DM2). For the treatment of DM2, thiazolidinedione drugs (TZDs) were proposed, but recent studies have shown that TZDs have several detrimental effects, such as weight gain, kidney enlargement (hypertrophy), fluid retention, increased risk of bone fractures, and potential harm to the liver (hepatotoxicity). That is why a new molecule is needed to treat DM2. OBJECTIVE: The current research aimed to assess the efficacy of ß-Sitosterol from methanolic extract of Zingiber roseum in managing diabetes via PPARγ modulation. METHODS: Zingiber roseum was extracted using methanol, and GC-MS was employed to analyze the extract. Through homology modeling, PPARγ structure was predicted. Molecular docking, MD simulation, free binding energies, QSAR, ADMET, and bioactivity and toxicity scores were all used during the in-depth computer-based research. RESULTS: Clinically, agonists of synthetic thiazolidinedione (TZDs) have been used therapeutically to treat DM2, but these TZDs are associated with significant risks. Hence, GC-MS identified phytochemicals to search for a new PPAR-γ agonist. Based on the in-silico investigation, ß-sitosterol was found to have a higher binding affinity (-8.9 kcal/mol) than standard drugs. MD simulations and MMGBSA analysis also demonstrated that ß-sitosterol bound to the PPAR-γ active site stably. CONCLUSION: It can be concluded that ß-sitosterol from Z. roseum attenuates Type-II diabetes by modulating PPARγ activity.

Therapeutic Viewpoint on Rat Models of Locomotion Abnormalities and Neurobiological Indicators in Parkinson's Disease.

BACKGROUND: Locomotion problems in Parkinson's syndrome are still a research and treatment difficulty. With the recent introduction of brain stimulation or neuromodulation equipment that is sufficient to monitor activity in the brain using electrodes placed on the scalp, new locomotion investigations in patients having the capacity to move freely have sprung up. OBJECTIVE: This study aimed to find rat models and locomotion-connected neuronal indicators and use them all over a closed-loop system to enhance the future and present treatment options available for Parkinson's disease. METHODS: Various publications on locomotor abnormalities, Parkinson's disease, animal models, and other topics have been searched using several search engines, such as Google Scholar, Web of Science, Research Gate, and PubMed. RESULTS: Based on the literature, we can conclude that animal models are used for further investigating the locomotion connectivity deficiencies of many biological measuring devices and attempting to address unanswered concerns from clinical and non-clinical research. However, translational validity is required for rat models to contribute to the improvement of upcoming neurostimulation-based medicines. This review discusses the most successful methods for modelling Parkinson's locomotion in rats. CONCLUSION: This review article has examined how scientific clinical experiments lead to localised central nervous system injuries in rats, as well as how the associated motor deficits and connection oscillations reflect this. This evolutionary process of therapeutic interventions may help to improve locomotion- based treatment and management of Parkinson's syndrome in the upcoming years.

Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice.

Currently deployed SARS-CoV-2 vaccines all require storage at refrigerated or sub-zero temperatures. We demonstrate that after month-long incubation at 37 °C, solubilization, and formulation with squalene-in-water emulsion adjuvant, a stabilized receptor binding domain retains immunogenicity and protective efficacy. We also examine the effects of trimerization of the stabilized RBD, as well as of additional adjuvants, on both B and T-cell responses. The additional emulsion or liposome-based adjuvants contained a synthetic TLR-4 ligand and/or the saponin QS-21. Trimerization enhanced immunogenicity, with significant antibody titers detectable after a single immunization. Saponin-containing adjuvants elicited enhanced immunogenicity relative to both emulsion and aluminum hydroxide adjuvanted formulations lacking these immunostimulants. Trimeric RBD formulated with liposomal based adjuvant containing both TLR-4 ligand and saponin elicited a strongly Th1 biased response, with ~10-fold higher neutralization titers than the corresponding aluminum hydroxide adjuvanted formulation. The SARS-CoV-2 virus is now endemic in humans, and it is likely that periodic updating of vaccine formulations in response to viral evolution will continue to be required to protect vulnerable individuals. In this context, it is desirable to have efficacious, thermostable vaccine formulations to facilitate widespread vaccine coverage, including in low- and middle-income countries, where global access rights to clinically de-risked adjuvants will be important moving forward.

Review of antibiotic use and resistance in food animal production in WHO South-East Asia Region.

Antimicrobial resistance is an emerging global threat to public health. The resistant bacteria in food animals can be transferred to humans through the food chain. Limited information on antimicrobial usage and resistance in food animals is available in Southeast Asia due to inadequate monitoring or surveillance systems. A literature review was conducted on antimicrobial use and resistance in food animal production in Southeast Asia for the period 2011-2020, to assess the scope and extent of antibiotic use and resistance. The countries included in the study were Bangladesh, Bhutan, Democratic People's Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste. The information was categorised by country, production type and findings regarding antibiotic use and resistance. A total of 108 publications were included in the review. Results showed widespread use of critically and highly important antibiotics in livestock, poultry and aquacultured fish and their products. To curb the growing threat of antibiotic resistance, Southeast Asian countries need to strengthen surveillance and regulatory controls of antimicrobial use in food animal production through "One Health" approach.

Bacillus Calmette-Guérin Vaccine Attenuates Haloperidol-Induced TD-like Behavioral and Neurochemical Alteration in Experimental Rats.

Tardive dyskinesia (TD) is a hyperkinetic movement disorder that displays unusual involuntary movement along with orofacial dysfunction. It is predominantly associated with the long-term use of antipsychotic medications, particularly typical or first-generation antipsychotic drugs such as haloperidol. Oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis are major pathophysiological mechanisms of TD. The BCG vaccine has been reported to suppress inflammation, oxidative stress, and apoptosis and exert neuroprotection via several mechanisms. Our study aimed to confirm the neuroprotective effect of the BCG vaccine against haloperidol-induced TD-like symptoms in rats. The rats were given haloperidol (1 mg/kg, i.p.) for 21 days after 1 h single administration of the BCG vaccine (2 × 107 cfu). Various behavioral parameters for orofacial dyskinesia and locomotor activity were assessed on the 14th and 21st days after haloperidol injection. On the 22nd day, all rats were euthanized, and the striatum was isolated to estimate the biochemical, apoptotic, inflammatory, and neurotransmitter levels. The administration of the BCG vaccine reversed orofacial dyskinesia and improved motor function in regard to haloperidol-induced TD-like symptoms in rats. The BCG vaccine also enhanced the levels of antioxidant enzymes (SOD, GSH) and reduced prooxidants (MDA, nitrite) and pro-apoptotic markers (Cas-3, Cas-6, Cas-9) in rat brains. Besides this, BCG treatment also restored the neurotransmitter (DA, NE, 5-HT) levels and decreased the levels of HVA in the striatum. The study findings suggest that the BCG vaccine has antioxidant, antiapoptotic, and neuromodulatory properties that could be relevant in the management of TD.

Assessing and Prioritizing Zoonotic Diseases in Punjab, India: A One Health Approach.

Zoonotic diseases have a significant impact on both human and animal health globally. The present study was planned to prioritize the zoonoses in Punjab state of India. To develop a zoonotic disease prioritization scoring system, a comprehensive approach has been taken, including literature review, key person interviews with animal health experts (n = 12) and medical professionals (n = 7), and nine focus group discussions (FGDs) with veterinary academicians, medical professionals, and field veterinary doctors. The scoring system comprises of seven major criteria, each assigned a weightage score (ws): prevalence/incidence of the disease (ws = 0.20), severity of illnesses in humans (ws = 0.18), epidemic potential (ws = 0.16), socio-economic burden (ws = 0.16), availability of effective control and prevention measures (ws = 0.15), inter-sectoral collaborations (ws = 0.1), and bioterrorism potential (ws = 0.05). The finalized scoring system, accompanied by a list of 15 selected zoonotic diseases, was implemented among a group of 23 professionals engaged in zoonoses research (n = 7), animal health (n = 10), and medical health (n = 6) to determine their prioritization. The zoonotic diseases prioritized for the Punjab (India) included, Brucellosis (0.70) > Rabies (0.69) > Anthrax (0.64) > Leptospirosis (0.62) = Toxoplasmosis (0.62) = Highly Pathogenic Avian Influenza (HPAI) (0.62) > Bovine tuberculosis (0.61) > Q fever (0.60) > Cysticercosis (0.59) > Listeriosis (0.58) > Crimean-Congo haemorrhagic fever (CCHF) (0.57) > Japanese encephalitis (0.56) = Echinococcosis (0.56) > Dermatophytosis (0.53) > and Scrub typhus (0.48), respectively. Higher priority is suggested for endemic zoonoses (e.g., brucellosis and rabies) as compared to those with epidemic potential (e.g., CCHF, HPAI etc.) in Punjab. Results of the current study will help in the development of targeted control and prevention strategies for zoonotic diseases in Punjab and other geographical regions facing similar challenges.

Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants.

With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly reactive immune responses that could improve protection. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Immunogens were expressed as soluble proteins with approximately fivefold higher purified yield than the Spike ectodomain and formulated along with Squalene-in-water emulsion (SWE) adjuvant. Immunization with S2 alone failed to elicit a neutralizing immune response, but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant. In hamsters, SWE-formulated RS2 (a genetic fusion of stabilized RBD with S2) showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations. Despite being based on the ancestral Wuhan strain of SARS-CoV-2, RS2 elicited broad neutralization, including against Omicron variants (BA.1, BA.5 and BF.7), and the clade 1a WIV-1 and SARS-CoV-1 strains. RS2 elicited sera showed enhanced competition with both S2 directed and RBD Class 4 directed broadly neutralizing antibodies, relative to RBD and Spike elicited sera. When lyophilized, RS2 retained antigenicity and immunogenicity even after incubation at 37 °C for a month. The data collectively suggest that the RS2 immunogen is a promising modality to combat SARS-CoV-2 variants.

Mutations in S2 subunit of SARS-CoV-2 Omicron spike strongly influence its conformation, fusogenicity, and neutralization sensitivity.

IMPORTANCE: The Omicron subvariants have substantially evaded host-neutralizing antibodies and adopted an endosomal route of entry. The virus has acquired several mutations in the receptor binding domain and N-terminal domain of S1 subunit, but remarkably, also incorporated mutations in S2 which are fixed in Omicron sub-lineage. Here, we found that the mutations in the S2 subunit affect the structural and biological properties such as neutralization escape, entry route, fusogenicity, and protease requirement. In vivo, these mutations may have significant roles in tropism and replication. A detailed understanding of the effects of S2 mutations on Spike function, immune evasion, and viral entry would inform the vaccine design, as well as therapeutic interventions aiming to block the essential proteases for virus entry. Thus, our study has identified the crucial role of S2 mutations in stabilizing the Omicron spike and modulating neutralization resistance to antibodies targeting the S1 subunit.

Treatment of diabetic complications: do flavonoids holds the keys?

Diabetes mellitus (DM) is an endocrinological disorder in which blood sugar levels get elevated and if unmanaged, it leads to several critical complications. Existing therapies or drugs are not able to attain absolute control of DM. Moreover, associated side/adverse effects associated with pharmacotherapy further worsen the Quality of life of patients. Present review is focused on therapeutical potential of flavonoids in management of diabetes and diabetic complications. Plenteous literature has established significant potential of flavonoids in the treatment of diabetes and diabetic complications. A number of flavonoids are found to be effective in treatment of not only diabetes but progression of diabetic complication was also found to be attenuated with the use of flavonoids. Moreover, SAR studies of some flavonoids also indicated the that efficacy of flavonoids is increased with a change in functional group of flavonoids in the treatment of diabetes and diabetic complications. A number of clinical trials are into action to investigate the therapeutic potential of flavonoids as first-line drugs or as adjuvants for treatment of diabetes and diabetic complications.. Owing to their diverse mechanism of action, efficacy and safety, flavonoids may be conscripted as potential candidate for treatment of diabetic complications.

Cucurbita pepo seeds improve peripheral neuropathy in diabetic rats by modulating the inflammation and oxidative stress in rats.

BACKGROUND: Cucurbita pepo (C. pepo) is cultivated and used traditionally as vegetable as well as medicine in different parts of the world. The aim of current study was to investigate the potential of C. pepo in attenuation of diabetic neuropathy via using streptozotocin (STZ)-induced diabetes model in male wistar rats. MATERIALS AND METHODS: Diabetic neuropathy was induced by administration of STZ; 65 mg/kg, i.p. and Nicotinamide (NAD; 230 mg/kg i.p.) and assessed by measuring thermal hyperalgesia, mechanical hyperalgesia and motor nerve conduction velocity (MNCV) in experimental animals. Treatment with different doses of (100, 200 and 400 mg/kg, p.o.) petroleum ether extract of C. pepo (CPE) and hydroethanolic extract of C. pepo (CHE) was started from the 60th day of STZ/NAD administration and continued upto 90th day. RESULTS: CPE and CHE significantly attenuated the behavioural changes including hyperalgesia, allodynia and MNCV linked to diabetic neuropathy. Moreover, the oxidative stress and level of TNF-α, TGF-ß and IL-1ß was found to be significantly attenuated in experimental animals. CONCLUSION: Thus C. pepo might ameliorate the progression of diabetic neuropathy via modulation of chronic hyperglycemia and therefore and have therapeutic potential for treatment of diabetic neuropathic pain.

Alkaloids as Potential Anti-HIV Agents.

BACKGROUND: Alkaloids are nitrogen-containing compounds that are naturally occurring and have a variety of biological activities, including antimicrobial properties. In this study, the authors used a molecular docking approach to evaluate the anti-HIV potential of 64 alkaloids. METHODS: The authors used the Molegro Virtual Docker software to dock the alkaloids into the active sites of three HIV enzymes: protease, integrase, and non-nucleoside reverse transcriptase (NNRT). The docking scores were used to assess the potential of the alkaloids to inhibit the enzymes. RESULTS: The results showed the alkaloids to have good potential to inhibit the enzymes. Tubocurarine and reserpine were found to be the most potent alkaloids, with docking scores of -123.776 and - 114.956, respectively. CONCLUSION: The authors concluded that tubocurarine and reserpine could be further promoted as potential lead molecules for the development of new anti-HIV drugs.

Monitoring of antimicrobial usage among adult bovines in dairy herds of Punjab, India: A quantitative analysis of pattern and frequency.

The present study aimed to evaluate the antimicrobial usage (AMU) pattern in dairy herds of Punjab, India. The on-farm quantification of AMU in adult bovine animals by the manual collection of empty drug containers ("bin method") along with the records of the treatment was carried out in 38 dairy farms involving 1010 adult bovines for 1 year from July 2020 to June 2021. The farm owners were asked to record the antibiotic treatments as well as to deposit empty antibiotic packaging/vials into the provided bins placed at the farms. A total of 14 different antibiotic agents in 265 commercial antibiotic products were administered to the dairy herds during the study. A total of 179 (67.55%) administered products contained antimicrobials of "critical importance" as per the World Health Organization (WHO). Mastitis (54.72%), followed by the treatment of fever (19.62%), reproductive problems (15.47%), and diarrhea (3.40%) accounted for the majority of drugs administered in the herds during the study period. The most commonly used antibiotics were enrofloxacin (89.47% herds; 21.51% products), followed by ceftriaxone (50% herds; 12.83% products), amoxicillin (50% herds; 12.83% products), oxytetracycline (55.26% herds; 11.70% products), and procaine penicillin (47.37% herds; 12.83% products). The highest quantity of AMU [in terms of antimicrobial drug use rate (ADUR)] was observed for ceftiofur, followed by ceftriaxone, procaine benzyl penicillin ceftizoxime, enrofloxacin, cefoperazone, amoxicillin and ampicillin. A total of 125 (47.17%) products contained "highest priority critically important antimicrobials" (HPCIA) and 54 (20.37%) products contained "high priority critically important antimicrobials". In terms of overall number of animal daily doses (nADD), the highest priority critically important antimicrobials (HPCIA) of the WHO such as third-generation cephalosporins and quinolones, respectively accounted for 44.64 and 22.35% of the total antibiotic use in the herds. The bin method offers an alternative to monitoring AMU as a more accessible approach for recording the actual consumption of antimicrobials. The present study, to the best of our knowledge, is the first of its kind to provide an overview of the qualitative and quantitative estimate of AMU among adult bovines from India.

Neutralizing Efficacy of Encapsulin Nanoparticles against SARS-CoV2 Variants of Concern.

Rapid emergence of the SARS-CoV-2 variants has dampened the protective efficacy of existing authorized vaccines. Nanoparticle platforms offer a means to improve vaccine immunogenicity by presenting multiple copies of desired antigens in a repetitive manner which closely mimics natural infection. We have applied nanoparticle display combined with the SpyTag-SpyCatcher system to design encapsulin-mRBD, a nanoparticle vaccine displaying 180 copies of the monomeric SARS-CoV-2 spike receptor-binding domain (RBD). Here we show that encapsulin-mRBD is strongly antigenic and thermotolerant for long durations. After two immunizations, squalene-in-water emulsion (SWE)-adjuvanted encapsulin-mRBD in mice induces potent and comparable neutralizing antibody titers of 105 against wild-type (B.1), alpha, beta, and delta variants of concern. Sera also neutralizes the recent Omicron with appreciable neutralization titers, and significant neutralization is observed even after a single immunization.

Biophysical Correlates of Enhanced Immunogenicity of a Stabilized Variant of the Receptor Binding Domain of SARS-CoV-2.

The receptor binding domain (RBD) of SARS-CoV-2 is the primary target of neutralizing antibodies. We have previously reported the design and characterization of a mammalian cell expressed RBD derivative, mRBD1-3.2, that has higher thermal stability and greatly enhanced immunogenicity relative to the wild type mRBD. The protein is highly thermotolerant and immunogenic and is being explored for use in room temperature stable Covid-19 vaccine formulations. In the current study, we have investigated the folding pathway of both WT and stabilized RBD. It was found that chemical denaturation of RBD proceeds through a stable equilibrium intermediate. Thermal and chemical denaturation is reversible, as assayed by binding to the receptor ACE2. Unusually, in its native state, RBD binds to the hydrophobic probe ANS, and enhanced ANS binding is observed for the equilibrium intermediate state. Further characterization of the folding of mRBD1-3.2, both in solution and after reconstitution of lyophilized protein stored for a month at 37 °C, revealed a higher stability represented by higher Cm, faster refolding, slower unfolding, and enhanced resistance to proteolytic cleavage relative to WT. In contrast to WT RBD, the mutant showed decreased interaction with the hydrophobic moiety linoleic acid. Collectively, these data suggest that the enhanced immunogenicity results from reduced conformational fluctuations that likely enhance in vivo half-life as well as reduce the exposure of irrelevant non-neutralizing epitopes to the immune system.

Characterization of chicken eggs associated Escherichia coli and Staphylococcus aureus for biofilm production and antimicrobial resistance traits.

The present study assessed the prevalence, virulence characteristics, antimicrobial resistance and biofilm-forming ability of E. coli and S. aureus recovered from egg samples in Ludhiana, Punjab. A total of 393 samples from hatcheries (n = 238), retail shops (n = 94), and households (n = 61) were collected. The prevalence of E. coli was observed as 11.70% and 9.16% for S. aureus. A total of 41.30% of E. coli isolates were positive for aggR gene and 52.17% were for fimA gene; while 36.11% of the S. aureus isolates were positive for coa gene. A high proportion of E. coli (76.10%) and S. aureus (69.44%) isolates were resistant toward ≥3 tested antibiotic classes. A total of 39.13% of E. coli isolates were moderate biofilm former, whereas the majority of the S. aureus (41.67%) were weak biofilm former. No significant difference regarding biofilm formation was observed between MDR and non-MDR isolates of E. coli and S. aureus. Biofilm genes viz., fimC and crl were reported in 43.47% and 80.43% of E. coli isolates, respectively; while icaA and icaD genes were reported in 58.34% and 47.22% of S. aureus isolates, respectively. A strong metabolic activity among 52.17% of E. coli and 41.66% of S. aureus isolates was observed using XTT assay. The present study highlights the need for applied food safety measures across the egg production chain of the region to prevent the development of MDR strains and biofilms.

Opportunities and challenges in application of artificial intelligence in pharmacology.

Artificial intelligence (AI) is a machine science that can mimic human behaviour like intelligent analysis of data. AI functions with specialized algorithms and integrates with deep and machine learning. Living in the digital world can generate a huge amount of medical data every day. Therefore, we need an automated and reliable evaluation tool that can make decisions more accurately and faster. Machine learning has the potential to learn, understand and analyse the data used in healthcare systems. In the last few years, AI is known to be employed in various fields in pharmaceutical science especially in pharmacological research. It helps in the analysis of preclinical (laboratory animals) and clinical (in human) trial data. AI also plays important role in various processes such as drug discovery/manufacturing, diagnosis of big data for disease identification, personalized treatment, clinical trial research, radiotherapy, surgical robotics, smart electronic health records, and epidemic outbreak prediction. Moreover, AI has been used in the evaluation of biomarkers and diseases. In this review, we explain various models and general processes of machine learning and their role in pharmacological science. Therefore, AI with deep learning and machine learning could be relevant in pharmacological research.

Ecological and human health risk assessment of metals in soils and wheat along Sutlej river (India).

Heavy metal (HMs) entry into soil affects the food chain, which is of great worry for human well-being hazards. In order to study the association of HMs in soil-plant system, surface (0-0.15 m) soil and wheat grain samples were collected within five km buffer zone of Sutlej river in Punjab (India). These samples were analysed for total arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), cobalt (Co), iron (Fe), manganese (Mn), nickle (Ni), lead (Pb), and zinc (Zn). Among all the HMs in soil and grain samples, the concentration of total Fe was maximum and As was minimum. The HM contamination of soils was assessed using contamination factor (CF), enrichment factor (EF), potential ecological risk (Er) and modified potential ecological risk (mEr). The CF, EF, Er and mEr were highest for Cd in soils. The bioaccumulation metal factor was highest for Zn and lowest for Ni in wheat grain. There was a significant (p < 0.05) positive relationship between HM concentration in soils and wheat grains indicating the health risk due to consumption of wheat cultivated around the five km buffer of the Sutlej river. The carcinogenic and non-carcinogenic risk due to ingestion of wheat grain were higher from Cd and Pb, respectively. These results are helpful for devising the remediation approaches to decrease the multi-metal contamination in soils and plants, and the epidemiological ways to preclude the human health risk from HM contamination.