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Diabetes mellitus is a chronic disease which causes complications in a large population worldwide. Traditionally, medicinal plants possess numerous bioactive compounds to treat chronic diseases. In this study, the bioactive compounds in Cucumis pubescens Willd. were screened computationally to treat diabetes. Ten ligand molecules from C. pubescens Willd. plant fruit were selected from GC-MS analysis. The target proteins like Lipase-related Protein 2 (2OXE), α – amylase (2QV4) and β – Glucosidase (2ZOX) were retrieved from the PDB databank. The proteins have been selected based on their role in anti-diabetic activity. All ten ligands were docked with all three proteins to identify the suitable ligand possessing high binding energy. The ligand (4H-Pyran-4-one, 2,3-Dihydro 3,5-Dihydroxy-6-Methyl) had a maximum binding energy of -4.3 kcal/mol and -4.4 kcal/mol with the targets 2OXE and 2ZOX respectively. The ligand molecule 1,4-dimethyl-2,3-diazabicyclo[2.2.1]hept-2-ene produced the highest binding energy of -4.7 kcal/mol with 2QV4. The predicted active phytochemicals can be used as natural drug molecules to treat diabetes mellitus in future.

Unmanned aerial vehicles (UAVs) represent a cutting-edge technology that holds the promise of revolutionizing the conventional tasks carried out in the realm of agriculture. On a global scale, UAVs are gaining prominence for pesticide applications, particularly with a focus on utilizing low spray volumes. Nevertheless, there remains a notable gap in research concerning the impacts of employing low spray volumes on herbicide efficacy. Hence, multi-location field studies were conducted at Agricultural Research Station, Bhavanisagar and Wetland Station, Coimbatore, Tamil Nadu, India in 2022 to evaluate the impact of different spray volumes using UAV and Knapsack Manual Sprayer (KMS) on droplet deposition, droplet density, and weed control efficacy. The treatments included UAV sprays at 30 and 45 L ha-1, as well as KMS at 500 L ha-1, with a weedy check as a control. Bispyribac-sodium 10% SC was applied at a rate of 35 g a.i ha-1 during the 2-to 3-leaf stage of the crops. The results revealed that droplet deposition, area coverage, and volume median diameter were affected by sprayer type (UAV and KMS). However, the two spray volumes tested using the UAV method provided similar droplet parameters. The KMS system at 500 L ha-1 exhibited the highest droplet deposition, while the UAV system achieved better droplet distribution at a spray volume of 30 L ha-1. Remarkably, the UAV system at 30 L ha-1 demonstrated effective weed control, which was statistically comparable to the KMS system at 500 L ha-1. These findings emphasize that the UAV spraying system with a spray volume of 30 L ha-1, delivering effective weed control while utilizing less carrier volume compared to the manual knapsack spraying method. Thus, the UAV spray system has great potential as a viable alternative to manual knapsack spraying for herbicide application in direct-seeded rice. [ABSTRACT FROM AUTHOR]

Introduction: Vitex negundo has a myriad of medicinal uses, such as antioxidant, analgesic and anthelminthic properties, and it is used for dysmenorrhoea. The plant contains various phytochemicals, such as flavonoids, vitamins and casticin. All components of the plant are utilised medicinally due to the minimal occurrence of adverse drug reactions, making it a potential drug target for various chronic diseases. However, the role of this plant in neurodegenerative disorders, such as Alzheimer's Disease (AD), has not yet been extensively studied. Aim: To evaluate the in-silico and in-vitro activity of the anti-Alzheimer properties of the Methanolic Extract of Vitex negundo (MEVN) leaves. Materials and Methods: The present in-silico docking study and in-vitro study were conducted in the Department of Pharmacology at Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu, India, over a period of two months. The in-silico analysis was performed to determine the intermolecular interactions between the ligand and protein of the top five scored molecules using PyMol software. To assess the Acetylcholinesterase (AChE) inhibitory property, the findings were presented as docking scores. Cell viability and cytotoxicity were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with results expressed as percentages for various concentrations: 6.25 µg/mL, 12.5 µg/mL, 25 µg/mL, 50 µg/mL, 75 µg/mL, and 100 µg/mL of MEVN. Results: The MEVN exhibited competitive inhibition of the AChE enzyme. There were active interactions between Agnuside, Isochlorogenic Acid B, Isochlorogenic Acid C, Kaempferol-3-O-rutinoside, and Quercetin found in the MEVN with AChE. The percentage of cell viability for the concentrations of 6.25 µg/mL, 12.5 µg/mL, 25 µg/mL, 50 µg/mL, 75 µg/mL, and 100 µg/mL, as determined by the MTT assay, was 98.62%, 98.86%, 97.19%, 96.66%, 91.86%, and 78.82%, respectively. The results indicated that MEVN does not exhibit any toxicity. Conclusion: The findings demonstrated that MEVN possesses AChE inhibitory properties and maintains cell viability, both of which are indicative of anti-Alzheimer activity. Therefore, MEVN can be further evaluated for its potential in preventing cell cytotoxicity and treating AD. [ABSTRACT FROM AUTHOR]

Gingipains (RgpA, RgpB, and Kgp) are major virulence factors of the periodontitis-causing bacterium Porphyromonas gingivalis. Isolation of gingipains from the crude protein sample of P. gingivalis is critical for studying the underlying invasion mechanism that contributes to periodontitis, Alzheimer’s disease, and cardiovascular disease (CVD). Chromatographic processes and molecular cloning are two standard techniques often used for gingipains isolation, which are time-consuming and costly. In this study, considerably easier methods based on passive-mediated diffusion gel elution and gelatin zymogram were used to isolate and characterize gingipains. Importantly, proteins eluted from Native-PAGE showed enzymatic activity for both Rgp and Kgp. In gelatin zymography, the proteins with a molecular size of ~50 kDa and above 245 kDa were suggested as arginine-specific gingipains. The passive diffusion-mediated gel elution method is a simpler technique to isolate gingipains from crude protein samples of P. gingivalis. By using covalent and highly specific gingipain inhibitors, gelatin zymography enabled an individual characterization of gingipain activity and inhibition. Finally, this protocol can be easily extended by adding the isoelectric focusing to further improve the protein separation and characterization.

Periodontal disease (PD) is multifactorial oral disease that damages tooth-supporting tissue. PD treatment includes proper oral hygiene, deep cleaning, antibiotics therapy, and surgery. Despite the availability of basic treatments, some of these are rendered undesirable in PD treatment due to side effects and expense. Therefore, the aim of the present study is to develop novel molecules to combat the PD triggering pathogens. The study involved the synthesis of 4-((5-(substituted-phenyl)-1,3,4-oxadiazol-2-yl)methoxy)benzamidine (5a-e), by condensation of 2-(4-carbamimidoylphenoxy)acetohydrazide (3) with different aromatic acids; and synthesis of 4-((4-(substituted benzylideneamino)-4H-1,2,4-triazol-3-yl)methoxy)benzamidine (6a-b) by treatment of compound 3 with CS2 followed by hydrazination and a Schiff reaction with different aromatic aldehydes. Synthesized compounds were characterized based on the NMR, FTIR, and mass spectrometric data. To assess the effectiveness of the newly synthesized compound in PD, new compounds were subjected to antimicrobial evaluation against P. gingivalis and E. coli using the micro-broth dilution method. Synthesized compounds were also subjected to cytotoxicity evaluation against HEK-293 cells using an MTT assay. The present study revealed the successful synthesis of heterocyclic derivatives of benzamidine with significant inhibitory potential against P. gingivalis and E. coli. Synthesized compounds exhibited minimal to the absence of cytotoxicity. Significant antimicrobial potential and least/no cytotoxicity of new heterocyclic analogs of benzamidine against PD-triggering bacteria supports their potential application in PD treatment.

Background: Lung cancer is the most reported cancer worldwide and therapeutic resistance poses a major challenge. This in silico molecular docking and molecular dynamic simulation study was carried out to evaluate the binding affinity and stability of molecular interactions between the phytochemical Matairesinol and the molecular targets in Non-Small Cell Lung Carcinoma (NSCLC) which are implicated in the pathogenesis and development of therapeutic resistance, thereby exploring its potential anticancer activity in NSCLC. Materials and Methods: The three-dimensional structure of Matairesinol was obtained from the PubChem database. The three-dimensional protein structures of target proteins were obtained from Protein Data Bank. DOCK6 software package was used for the preparation of ligands and proteins. For the molecular dynamics study, the OPLS-2005 force field implemented in Desmond routine of Schrödinger software suite was used and the study was performed till 100 ns. Binding free energy (MM/GBSA), Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) values of all complexes were determined. Principal component analysis and Detailed Cross-Correlation Maps were carried out. Results and Discussion: Matairesinol showed good binding energies and docking scores with all the targets tested in this study with relatively stable molecular interactions, with the highest affinity shown towards ALK. The interactions with EGFR wild type, KRAS G12C mutant protein, VEGFR2, C-MET and ALK were especially of high stability. Conclusion: The results of this study reveal the potential anti-cancer activity of Matairesinol in NSCLC with the possible added benefit of treating therapeutic resistance. Further studies are required to fully evaluate the target profile of Matairesinol in NSCLC and its therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Periodontal disease (PD) is complex polymicrobial disease which destroys tooth-supporting tissue. Although various synthetic inhibitors of periodontitis-triggering pathogens have been recognized, their undesirable side effects limit their application. Hence, the present study intended to perform the synthesis, characterization, antimicrobial evaluation, and cytotoxicity analysis of novel benzamidine analogues (NBA). This study involved the synthesis of novel imino bases of benzamidine (4a–c), by reacting different aromatic aldehydes with 2-(4-carbamimidoylphenoxy) acetohydrazide (3), which was synthesized by the hydrazination of ethyl 2-(4-carbamimidoylphenoxy) acetate (2), the derivative of 4-hydroxybenzene carboximidamide (1). This was followed by characterization using FTIR, 1H, 13C NMR and mass spectrometry. All synthesized compounds were further tested for antimicrobial potential against PD-triggering pathogens by the micro broth dilution method. The cytotoxicity analysis of the NBA against HEK 293 cells was conducted using an MTT assay. The present study resulted in a successful synthesis of NBA and elucidated their structures. The synthesized NBA exhibited significant antimicrobial activity values between 31.25 and 125 µg/mL against tested pathogens. All NBA exhibited weak cytotoxicity against HEK 293 cells at 7.81 µg, equally to chlorhexidine at 0.2%. The significant antimicrobial activity of NBA against PD-triggering pathogens supports their potential application in periodontitis treatment.

Introduction: India has the highest burden of animal bite cases globally, with a large proportion of the population affected by dog bites. India is endemic for rabies and accounts for 36% of the world's rabies deaths. Mortality can be prevented by Post-Exposure Prophylaxis (PEP) with effective vaccines that are available. Vaccines are provided free of charge in Government hospitals. Aim: To estimate the compliance rate of Anti-Rabies Vaccine (ARV) regimen managed by the intradermal route. Materials and Methods: This was a cross-sectional recordbased study from the ARV Register of Government Hospital, Gummidipoondi, Tamil Nadu, India. The victims of animal bite cases attending the hospital for the ARV regimen for a month were selected from the register to assess adherence to the full course updated Thai Red Cross regimen and identify any constraint factors hindering them from completing the course. Results: Out of 108 patients, 79 completed the full course ARV regimen, resulting in a compliance rate of 73.1%. Factors such as the distance of the hospital, timings, and forgotten dates were identified as major constraints. Conclusion: The compliance rate was found to be moderate, with constraint factors like forgotten dates and the distance of the hospital being significant hindrances to compliance. This highlights the importance of strengthening awareness through sensitisation programs and health education in both urban and rural areas to achieve a rabies-free India. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is a serious psychological condition associated with social stigma, psychiatric co-morbidity, and a high economic burden. It is pertinent to develop novel treatment methods given the ever-evolving nature of the disease. Recently, various newer Antiepileptic Drugs (AEDs) have been under study, among which a newer targeted modality consists of SV2A receptors. Aim: To compare the antioxidant properties or free radical scavenging activity of the newer heterogeneous AEDs acting on the SV2A receptors, namely Levetiracetam (LEV) and Brivaracetam (BRV). Materials and Methods: This in-vitro study was conducted at Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India from July 2021 to August 2021. The study evaluated the antioxidant properties of LEV and BRV using various assays such as the Ferric Reducing Antioxidant Power (FRAP) test, DPPH (1,1-diphenyl-2-picrylhydrazyl) assay, Nitric Oxide (NO) radical scavenging assay, Superoxide Dismutase activity (SOD), and catalase activity. The obtained results were expressed using specific formulas related to the absorbance of the respective chemicals, along with the percentage of inhibition, and have been tabulated in Microsoft excel Sheet Version 16.16.27. Halfmaximal Inhibitory Concentration (IC50) values were calculated using scatter plot graphs. Results: The FRAP values for LEV were reported to be significantly higher compared to BRV at concentrations of 20, 40, 60, 80 μg/mL, while at 100 μg/mL, BRV showed better ferric reducing activity. Although both drugs exhibited antioxidant activity, the results clearly identified LEV as a better NO radical scavenger, with a percentage of inhibition reaching up to 80.52%. During the SOD assay, the percentage inhibition of superoxide generation by LEV was found to be 99.02%, while that of BRV was 97.07% at a concentration of 100 μg/mL. LEV (0.573) also showed a higher degradation of H2O2 per minute than BRV (0.065) at a concentration of 100 μg/mL. Conclusion: The results showed that both drugs, BRV and LEV, exhibited significant antioxidant capacity. However, LEV demonstrated increased antioxidant potency and efficacy compared to BRV. [ABSTRACT FROM AUTHOR]

Paclitaxel is a widely used cancer chemotherapeutic agent for many solid tumors; but peripheral neuropathy is a major limitation for its clinical use. Studies have demonstrated the usefulness of flavone derivatives in chemotherapy induced peripheral neuropathy. The present study evaluates the anti-neuropathic effect of 3', 4'-dihydroxyflavone on paclitaxel-induced peripheral neuropathy and the underlying mechanisms. Paclitaxel was administered to mice in a single dose of 10 mg/kg, i.p.The neuropathic behavioural parameters such as mechanical allodynia, cold allodynia and thermal hyperalgesia were assessed 24 h later. The test compound 3', 4'-dihydroxyflavone (50,100 or 200 mg/kg,s.c) was administered 30 min prior to the assessment of behavioral parameters. The possible mechanisms involving K ATP channels, adenosine and GABA A receptors were explored by employing suitable interacting drugs. Molecular docking studies to predict the binding interactions of 3', 4'-dihydroxyflavone at the above targets were also carried out. The test compound 3', 4'-dihydroxyflavoneexhibited a significant reduction in paw withdrawal response score in both mechanical and cold allodynia and also increased the tail flick response time in thermal hyperalgesia due to paclitaxel-induced neuropathy. The anti-neuropathic effect of 3', 4'-dihydroxyflavonewas significantly reversed by pre-treatment with glibenclamide, caffeine or bicuculline revealing the involvement of K ATP channels, adenosine and GABA A receptors respectively. Furthermore, the molecular docking studies indicated a favourable binding affinity and good H-bond interaction of 3', 4'-dihydroxyflavone at these targets. The findings of the present study suggests that, 3', 4'-dihydroxyflavone has anti-neuropathic effect against paclitaxel-induced peripheral neuropathy through mechanisms that involve K ATP channels, adenosine (A 3 ) and GABA A (α 2 subunit) receptors., (© 2023 Biomedical Informatics.)