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MB Ravi,1 Sowmya Srinivas,1 Ekaterina Silina,2 Soumee Sengupta,1 Tanvi Tekwani,1 Raghu Ram Achar3 1Department of Prosthodontics, JSS Dental College and Hospital, JSS Academy of Higher Education & Research, Mysuru, Karnataka, India; 2Department of Human Pathology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 3Division of Biochemistry, School of Life Sciences, JSS Academy of Higher Education & Research, Mysuru, Karnataka, IndiaCorrespondence: MB RaviDepartment of Prosthodontics, JSS Dental College and Hospital, JSS Academy of Higher Education & Research, Shri Shivarathreeshwara Nagar, Mysuru, Karnataka, 570015, IndiaEmail dr.ravimb@jssuni.edu.inAbstract: Mucormycosis, a rare fungal infection seen in diabetes, is now very frequent owing to the deadly triad of COVID-19 infection, diabetes, and rampant use of corticosteroids. Immediate management revolves around therapeutic drugs like antifungals, antibiotics, and aggressive surgical debridement. The cases described in the article explain prosthetic rehabilitation of maxillectomy defects. The findings focus on prosthetic rehabilitation of patients with acquired maxillectomy defects after mucormycotic necrosis post-COVID-19 infection and the techniques to overcome the complications like lack of supporting tissues and post-surgical microstomia. The maxillectomies were performed on patients who suffered a superinfection of mucormycosis after COVID-19 contraction and uncontrolled blood sugar levels. Case 1 elaborates a technique to overcome the complications like lack of supporting structures and microstomia by fabrication of sectional and hollow obturator prostheses using sectional impression technique and lost salt technique. Case 2 explains the management of an extensive defect with a mobile soft tissue flap and lone standing tooth by using a functional impression technique to gain retention and support from the remaining soft and hard tissues. Both the techniques overcome the clinical complications and give predictable outcomes. Prosthetic rehabilitation of such challenging cases needs modifications depending upon the clinical challenges encountered.Keywords: maxillectomy, microstomia, sectional impression, lost salt technique, functional impression

The present study was focused on exploring the efficient inhibitors of closed state (form) of type III effector Xanthomonas outer protein Q (XopQ) (PDB: 4P5F) from the 44 phytochemicals of Picrasma quassioides using cutting-edge computational analysis. Among them, Kumudine B showed excellent binding energy (-11.0 kcal/mol), followed by Picrasamide A, Quassidine I and Quassidine J with the targeted closed state of XopQ protein compared to the reference standard drug (Streptomycin). The molecular dynamics (MD) simulations performed at 300 ns validated the stability of top lead ligands (Kumudine B, Picrasamide A, and Quassidine I)-bound XopQ protein complex with slightly lower fluctuation than Streptomycin. The MM-PBSA calculation confirmed the strong interactions of top lead ligands (Kumudine B and QuassidineI) with XopQ protein, as they offered the least binding energy. The results of absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis confirmed that Quassidine I, Kumudine B and Picrasamide A were found to qualify most of the drug-likeness rules with excellent bioavailability scores compared to Streptomycin. Results of the computational studies suggested that Kumudine B, Picrasamide A, and Quassidine I could be considered potential compounds to design novel antibacterial drugs against X. oryzae infection. Further in vitro and in vivo antibacterial activities of Kumudine B, Picrasamide A, and Quassidine I are required to confirm their therapeutic potentiality in controlling the X. oryzae infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Revanasiddappa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chromobacterium violaceum an opportunistic human pathogenic bacterium, exhibits resistance to conventional antibiotics by exploiting its quorum sensing mechanism to regulate virulence factor expression. In light of this, disrupting the quorum sensing mechanism presents a promising avenue for treating infections caused by this pathogen. The study focused on using the cytoplasmic quorum sensing receptor CviR from C. violaceum as a model target to identify novel quorum sensing inhibitors from P. quassioides through in silico computational approaches. Molecular docking analyses unveiled that several phytochemicals derived from Picrasma quassioides exhibit the potential to inhibit quorum sensing by binding to CviR protein. Notably, the compounds such as Quassidine I (- 8.8 kcal/mol), Quassidine J (- 8.8 kcal/mol), Kumudine B (- 9.1 kcal/mol) and Picrasamide A (- 8.9 kcal/mol) exhibited high docking scores, indicating strong binding affinity to the CviR protein. The native ligand C6-HSL (N-hexanoyl-L-homoserine lactone) as a positive control/co-crystal inhibitor also demonstrated a significant binding energy of-7.7 kcal/mol. The molecular dynamics simulation for 200 ns showed the thermodynamic stability and binding affinity refinement of the top-ranked CviR inhibitor (Kumudine B) with its stable binding and minor fluctuations compared to positive control (C6-HSL). Pharmacokinetic predictions indicated that Kumudine B possesses favourable drug-like properties, which suggest its potential as a drug candidate. The study highlight Kumudine B as a potential agent for inhibiting the CviR protein in C. violaceum . The comprehensive evaluation of Kumudine B provides valuable insights into its pharmacological profiles, facilitating its assessment for diverse therapeutic applications and guiding future research activities, particularly as antibacterial agents for clinical drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Revanasiddappa, H. G., K. P., Natarajamurthy, K., Pradeep, Shivamallu, Elossaily, Achar, Silina, Stupin, Manturova, A. Shati, Y. Alfaifi, I. Elbehairi, Kestur Nagaraj, Mahadevamurthy and Kollur.)

Background: The COVID-19 pandemic which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a major global health crisis in recent years. Despite this, there have been few studies that have utilized reliable methods to assess changes in taste and smell perception. Therefore, our study aims at the number of fungiform papillae and objective measures of taste perception relationship among COVID-19 patients with olfactory and gustatory disorders., Materials and Methods: This was a cross-sectional analytical study in which 57 COVID-19 patients were recruited who confirmed the dysfunction of taste and smell. Objective assessment of the sense of taste was evaluated using four different standardized solution preparations, and the scores were given according to the patient's statements. Digitalized quantification of fungiform papillae was counted. The data were analyzed with the Pearson's correlation coefficient using the SPSS version. 23 [Licensed JSSAHER, Mysuru, Karnataka, India], and the level of significance was set at <0.001., Results: In terms of altered or reduced taste and smell, male patients exhibited a higher incidence compared to females. Compared to the sour taste, a substantial number of COVID-19 patients have displayed a notable decrease in their ability to taste sweet, salty, and bitter flavors. However, a statistically significant positive correlation was observed between taste scores and fungiform papillae density ( r = 0.518, P < 0.001)., Conclusion: Our Study demonstrated that the quantitative evaluation of taste perception and the count of fungiform papillae can serve as important indicators of SARS-CoV-2 infection, and could potentially help in the early detection and treatment of COVID-19 patients, as reduced taste function is a significant marker of the disease., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or nonfinancial in this article., (Copyright: © 2024 Dental Research Journal.)

The purpose of this study was to investigate the antimicrobial activity of citrate-stabilized sols of cerium oxide nanoparticles at different concentrations via different microbiological methods and to compare the effect with the peroxidase activity of nanoceria for the subsequent development of a regeneration-stimulating medical and/or veterinary wound-healing product providing new types of antimicrobial action. The object of this study was cerium oxide nanoparticles synthesized from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid (the size of the nanoparticles was 3-5 nm, and their aggregates were 60-130 nm). Nanoceria oxide sols with a wide range of concentrations (10 -1 -10 -6 M) as well as powder (the dry substance) were used. Both bacterial and fungal strains ( Bacillus subtilis , Bacillus cereus , Staphylococcus aureus , Pseudomonas aeruginosa , Escherichia coli , Proteus vulgaris , Candida albicans , Aspergillus brasielensis ) were used for the microbiological studies. The antimicrobial activity of nanoceria was investigated across a wide range of concentrations using three methods sequentially; the antimicrobial activity was studied by examining diffusion into agar, the serial dilution method was used to detect the minimum inhibitory and bactericidal concentrations, and, finally, gas chromatography with mass-selective detection was performed to study the inhibition of E. coli's growth. To study the redox activity of different concentrations of nanocerium, we studied the intensity of chemiluminescence in the oxidation reaction of luminol in the presence of hydrogen peroxide. As a result of this study's use of the agar diffusion and serial dilution methods followed by sowing, no significant evidence of antimicrobial activity was found. At the same time, in the current study of antimicrobial activity against E. coli strains using gas chromatography with mass spectrometry, the ability of nanoceria to significantly inhibit the growth and reproduction of microorganisms after 24 h and, in particular, after 48 h of incubation at a wide range of concentrations, 10 -2 -10 -5 M (48-95% reduction in the number of microbes with a significant dose-dependent effect) was determined as the optimum concentration. A reliable redox activity of nanoceria coated with citrate was established, increasing in proportion to the concentration, confirming the oxidative mechanism of the action of nanoceria. Thus, nanoceria have a dose-dependent bacteriostatic effect, which is most pronounced at concentrations of 10 -2 -10 -3 M. Unlike the effects of classical antiseptics, the effect was manifested from 2 days and increased during the observation. To study the antimicrobial activity of nanomaterials, it is advisable not to use classical qualitative and semi-quantitative methods; rather, the employment of more accurate quantitative methods is advised, in particular, gas chromatography-mass spectrometry, during several days of incubation.

The present study explores the epidermal growth factor receptor (EGFR) tyrosine kinase inhibition efficacy of secondary metabolites in Trichoderma spp. through molecular docking, molecular dynamics (MD) simulation and MM-PBSA approach. The result of molecular docking confirmed that out of 200 metabolites screened, three metabolites such as Harzianelactone A, Pretrichodermamide G and Aspochalasin M, potentially bound with the active binding site of EGFR tyrosine kinase domain(PDB ID: 1M17) with a threshold docking score of ≤- 9.0 kcal/mol when compared with the standard EGFR inhibitor (Erlotinib). The MD simulation was run to investigate the potential for stable complex formation in EGFR tyrosine kinase domain-unbound/lead metabolite (Aspochalasin M)-bound/standard inhibitor (Erlotinib)-bound complex. The MD simulation analysis at 100 ns revealed that Aspochalasin M formed the stable complex with EGFR. Besides, the in silico predication of pharmacokinetic properties further confirmed that Aspochalasin M qualified the drug-likeness rules with no harmful side effects (viz., hERG toxicity, hepatotoxicity and skin sensitization), non-mutagenicity and favourable logBB value. Moreover, the BOILED-Egg model predicted that Aspochalasin M showed a higher gastrointestinal absorption with improved bioavailability when administered orally and removed from the central nervous system (CNS). The results of the computational studies concluded that Aspochalasin M possessed significant efficacy in binding EGFR's active sites compared to the known standard inhibitor (Erlotinib). Therefore, Aspochalasin M can be used as a possible anticancer drug candidate and further in vitro and in vivo experimental validation of Aspochalasin M of Trichoderma spp. are required to determine its anticancer potential., Competing Interests: R.G.P. 2/183/44. The funders (R.G.P. 2/183/44) had a role in the preparation of the manuscript., (Copyright: © 2024 Gowtham et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Zinc oxide nanoparticles (ZnO-NPs) synthesized through biogenic methods have gained significant attention due to their unique properties and potential applications in various biological fields. Unlike chemical and physical approaches that may lead to environmental pollution, biogenic synthesis offers a greener alternative, minimizing hazardous environmental impacts. During biogenic synthesis, metabolites present in the biotic sources (like plants and microbes) serve as bio-reductants and bio-stabilizers. Among the biotic sources, microbes have emerged as a promising option for ZnO-NPs synthesis due to their numerous advantages, such as being environmentally friendly, non-toxic, biodegradable, and biocompatible. Various microbes like bacteria, actinomycetes, fungi, and yeast can be employed to synthesize ZnO-NPs. The synthesis can occur either intracellularly, within the microbial cells, or extracellularly, using proteins, enzymes, and other biomolecules secreted by the microbes. The main key advantage of biogenic synthesis is manipulating the reaction conditions to optimize the preferred shape and size of the ZnO-NPs. This control over the synthesis process allows tailoring the NPs for specific applications in various fields, including medicine, agriculture, environmental remediation, and more. Some potential applications include drug delivery systems, antibacterial agents, bioimaging, biosensors, and nano-fertilizers for improved crop growth. While the green synthesis of ZnO-NPs through microbes offers numerous benefits, it is essential to assess their toxicological effects, a critical aspect that requires thorough investigation to ensure their safe use in various applications. Overall, the presented review highlights the mechanism of biogenic synthesis of ZnO-NPs using microbes and their exploration of potential applications while emphasizing the importance of studying their toxicological effects to ensure a viable and environmentally friendly green strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Murali, Gowtham, Shilpa, Singh, Aiyaz, Sayyed, Shivamallu, Achar, Silina, Stupin, Manturova, Shati, Alfaifi, Elbehairi and Kollur.)

Breast cancer is a leading cause of mortality in women, and alternative therapies with fewer side effects are actively being explored. Breast cancer is a significant global health concern, and conventional treatments like radiotherapy and chemotherapy often have side effects. Medicinal plant extracts offer a promising avenue for the development of effective and safe anticancer therapies. Terminalia chebula , a plant known for its medicinal properties, was selected for investigation in this study. We aimed to assess the antiproliferative effects of TCF extract on breast cancer cells and explore the potential role of saccharopine, a phytochemical found in TCF, as an anticancer agent. MCF7 breast cancer cell lines were exposed to TCF extract, and cell viability and apoptosis assays were performed to evaluate the antiproliferative and apoptogenic effects. Molecular docking studies were conducted to assess the binding affinity of saccharopine with EGFRs. Molecular dynamics simulations and binding energy calculations were employed to analyze the stability of the EGFR-saccharopine complex. The TCF extract exhibited significant antiproliferative effects on MCF7 breast cancer cells and induced apoptosis in a dose-dependent manner. Molecular docking analysis revealed that saccharopine demonstrated a higher binding affinity with EGFR compared to the reference compound (17b-estradiol). The subsequent MDS simulations indicated stable binding patterns and conformation of the EGFR-saccharopine complex, suggesting a potential role in inhibiting EGFR-mediated signaling pathways. The investigation of Terminalia chebula fruit extract and its phytochemical saccharopine has revealed promising antiproliferative effects and a strong binding affinity with EGFR. These findings provide a foundation for future research aimed at isolating saccharopine and conducting in vivo studies to evaluate its potential as a targeted therapy for breast cancer. The development of novel anticancer agents from plant sources holds great promise in advancing the field of oncology and improving treatment outcomes for breast cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Reddy, Pradeep, S. M., Dharmashekar, G., M. R., Srinivasa, Shati, Alfaifi, Elbehairi, Achar, Silina, Stupin, Manturova, Shivamallu and Kollur.)

Background: Viscum orientale is a largely used parasitic plant with traditional medicinal properties. They are considered to possess the medicinal properties of host tree which they grow on. It's a least explored plant with ethanopharmacological importance. As a result, the current work aimed to investigate the biological effects of Viscum orientale extract and silver nanoparticles (AgNPs) generated from it., Methods: AgNPs synthesized using Viscum orientale plant extract and analysed on time dependent series and was characterized using Ultra Violet UV-visible spectra, Fourier Transform Infrared Spectroscopy FTIR, X-ray diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX), Scanning Electron Microscopy (SEM). Further using disc method anti-microbial assay was performed following antioxidation screening using 1,1-diphenyl-2-picryl-hydrazyl (DPPH), reducing power and nitric oxide content and heamgglutination with human blood., Results: On green synthesis using silver, the phyto contituents of plant Viscum orientale effectively reduced silver ions at 3-4 h of continuous stirring to form AgNPs. UV-vis spectra showed a typical peak of AgNPs at 480 nm. The FTIR analysis confirmed the covering of silver layers to bio-compounds of the extract. SEM analysis represented AgNPs as spherical morphologies ranging from 119-222 nm. AgNPs exhibited impressive zone of inhibition against Escherichia coli (8.1 ± 0.3 mm), Staphylococcus aureus (10.3 ± 0.3 mm), Bacillus subtilis (7.3 ± 0.3 mm), Bacillus cereus (8.2 ± 0.3 mm), Salmonella typhi (7.1 ± 0.2 mm). AgNps exhibited efficiency against DPPH at EC 50 value of 57.60 µg/ml. and reducing power at EC 50 of 53.42 µg/ml and nitric oxide scavenging of EC 50 of 56.01 µg/ml concentration. Further, anthelmintic activity results showed synthesized nanoparticles significant reduction in the paralysis time to 5.4 ± 0.3 min and death time to 6.5 ± 0.6 min in contrast to the individual factors. On hemagglutination using AgNPs, above 80 µg/ml of concentration showed very significant effect on comparison with water extract., Conclusion: Synthesized AgNPs using Viscum orientale water extract displayed versatile biological activity than individual extract. This study has forecasted a new path to explore more on this AgNPs for further research., (© 2023. The Author(s).)

In the present study, the binding affinity of 52 bioactive secondary metabolites from Wedelia trilobata towards the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein (PDB: 2W3L) structure was identified by using in silico molecular docking and molecular dynamics simulation. The molecular docking results demonstrated that the binding energies of docked compounds with Bcl-2 protein ranged from -5.3 kcal/mol to -10.1 kcal/mol. However, the lowest binding energy (-10.1 kcal/mol) was offered by Friedelin against Bcl-2 protein when compared to other metabolites and the standard drug Obatoclax (-8.4 kcal/mol). The molecular dynamics simulations revealed that the Friedelin-Bcl-2 protein complex was found to be stable throughout the simulation period of 100 ns. Overall, the predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of Friedelin are relatively better than Obatoclax, with the most noticeable differences in many parameters where Friedelin has no AMES toxicity, hepatotoxicity, and skin sensitization. The ADMET profiling of selected compounds supported their in silico drug-likeness properties. Based on the computational analyses, the present study concluded that Friedelin of W. trilobata was found to be the potential inhibitor of the Bcl-2 protein, which merits attention for further in vitro and in vivo studies before clinical trials.

Introduction: The use of plant extracts in the green synthesis of metallic nanoparticles is one of the simplest, most practical, economical, and ecologically friendly methods for avoiding the use of toxic chemicals. Method: Silver nanoparticles (AgNPs) were synthesized, employing a high-efficiency, non- toxic, cost-effective, green, and simple technique that included the use of Salacia oblonga root extract (SOR) as a capping agent compared to synthetic nanoparticles. The use of S. oblonga can be seen in traditional medicines for treating diabetes, obesity, rheumatism, gonorrhea, asthma, and hyperglycemia. The objectives of the current study were to green synthesize S. oblonga root extract silver nanoparticles (SOR-AgNPs), characterize them, and study their antioxidant, antibacterial, and antidiabetic activities. Result: The shape of SOR-AgNPs was spherical, at less than 99.8 nm in size, and exhibited a crystalline peak at XRD. The green synthesized SOR-AgNPs showed significant antioxidant properties like DPPH (80.64 μg/mL), reducing power capacity (81.09 ± SEM μg/mL), nitric oxide (96.58 μg/mL), and hydroxyl (58.38 μg/mL) radical scavenging activities. The MIC of SOR-AgNPs was lower in gram-positive bacteria. The SOR-AgNPs have displayed efficient inhibitory activity against α-amylase, with an EC50 of 58.38 μg/mL. Analysis of capping protein around the SOR-AgNPs showed a molecular weight of 30 kDa. Discussion: These SOR-AgNPs could be used as antibacterial and antidiabetic drugs in the future as it is cheap, non-toxic, and environmentally friendly. Bio-fabricated AgNPs had a significant impact on bacterial strains and could be used as a starting point for future antibacterial drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dugganaboyana, Kumar Mukunda, Jain, Kantharaju, Nithya, Ninganna, Ahalliya, Shati, Alfaifi, Elbehairi, Silina, Stupin, Velliyur Kanniappan, Achar, Shivamallu and Kollur.)

The current study investigates the effectiveness of phytocompounds from the whole green jackfruit flour methanol extract (JME) against obesity-linked diabetes mellitus using integrated network pharmacology and molecular modeling approach. Through network pharmacology, druglikeness and pharmacokinetics, molecular docking simulations, GO analysis, molecular dynamics simulations, and binding free energy analyses, it aims to look into the mechanism of the JME phytocompounds in the amelioration of obesity-linked diabetes mellitus. There are 15 predicted genes corresponding to the 11 oral bioactive compounds of JME. The most important of these 15 genes was MAPK3. According to the network analysis, the insulin signaling pathway has been predicted to have the strongest affinity to MAPK3 protein, which was chosen as the target. With regard to the molecular docking simulation, the greatest notable binding affinity for MAPK3 was discovered to be caffeic acid (-8.0 kJ/mol), deoxysappanone B 7,3'-dimethyl ether acetate (DBDEA) (-8.2 kJ/mol), and syringic acid (-8.5 kJ/mol). All the compounds were found to be stable inside the inhibitor binding pocket of the enzyme during molecular dynamics simulation. During binding free energy calculation, all the compounds chiefly used Van der Waal's free energy to bind with the target protein (caffeic acid: 102.296 kJ/mol, DBDEA: -104.268 kJ/mol, syringic acid: -100.171 kJ/mol). Based on these findings, it may be inferred that the reported JME phytocompounds could be used for in vitro and in vivo research, with the goal of targeting MAPK3 inhibition for the treatment of obesity-linked diabetes mellitus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Maradesha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The emerging interest in the field of coordination chemistry and their biological applications has created a novel impact in the field of chemical biology. With this motivation, in this work we have synthesized a novel benzimidazole derived imine ligand, 2-((E)-((1H-benzo[d]-2-yl)methylimino)methyl)-4-fluorophenol ( HBMF ) and its Co(III) and Cu(II) complexes. The metal complexes ( C1 - C4 ) were synthesized in 2:1 ( HBMF : metal ion) and 1:1:1 ( HBMF : metal ion: 1,10-phen) ratios. Structural elucidations of all the synthesized compounds were performed using FT-IR, UV-Visible, NMR, Mass spectroscopy and elemental analysis techniques. A combination of first principles calculations and molecular dynamics simulations was applied to computationally investigate the structural, reactive, and spectroscopic properties of the newly synthesized HBMF ligand and its complexes with copper and cobalt metal ions. Quantum-mechanical calculations in this study were based on the density functional theory (DFT), while molecular dynamics (MD) simulations were based on the OPLS4 force field. The DFT calculations were used to obtain the reactive and spectroscopic properties of the ligand and its complexes, while molecular dynamics (MD) simulations were used to address the ligand's reactivity with water. Further, the in vitro anti-proliferative activity of the compounds was tested against the A549, Ehrlich-Lettre ascites carcinoma (EAC), SIHA and NIH3T3 cell lines. The biological results depicted that the compound C4 , with molecular formula C 27 H 23 Cl 2 CoFN 5 O 3 exhibited profound anti-proliferative activity against the EAC cell line with a significant IC 50 value of 10 µm when compared to its parent ligand and other remaining metal complexes under study. Various assays of hematological parameters (alkaline phosphate, creatinine, urea, RBC and WBC) were performed, and significant results were obtained from the experiments. Furthermore, the effect of C4 on neovascularization was evaluated by stimulating the angiogenesis with rVEGF 165 , which was compared with non-tumor models. The EAC cells were cultured in vivo and administrated with 50 and 75 mg/kg of two doses and tumor parameters were evaluated.

A sequence of novel 2-(4-benzoyl-2-methyl-phenoxy)-N-(3-chloro-2-oxo-4-phenyl-azetidin-1-yl)-acetamide analogues 9(a−n) were synthesized by multistep synthesis. The newly synthesized compounds were well characterized, and their antimicrobial activities were carried out by disc diffusion and broth dilution methods. Further, all the novel series of compounds (9a−n), were tested against a variety of bacterial and fungal strains in comparison to Ketoconazole, Chloramphenicol, and Amoxicillin as standard drugs, respectively. Compounds 9a, 9e, and 9g as a lead molecule demonstrated a good inhibition against tested strains. Further, molecular docking studies have been performed for the potent compounds to check the three-dimensional geometrical view of the ligand binding to the targeted proteins.

The present work describes the chemical preparation of Schiff bases derived from 4,4'-diaminodiphenyl sulfone (L 1 -L 5 ) and their Co(II) metal complexes. The evaluation of antimicrobial and anticancer activities against MCF-7 cell line and human lung cancer cell line A-549 was performed. The aforementioned synthesized compounds are characterized by spectroscopic techniques and elemental analysis confirms successful synthesis. The results from the above analytical techniques revealed that the complexes are in an octahedral geometry. The antimicrobial activity of the synthesized Schiff base ligands and their metal complexes under study was carried out by using the agar well diffusion method. The ligand and complex interactions for biological targets were predicted using molecular docking and high binding affinities. Further, the anticancer properties of the synthesized compounds are performed against the MCF-7 cell line and human lung cancer cell line A-549 using adriamycin as the standard drug.

Diabetic foot ulcers are an extremely urgent medical and social problem throughout the world. The purpose of this study was to analyse the histological and immunohistochemical features of tissues and cells of different sections of wounds taken during the primary surgical treatment of chronic wounds in patients with diabetic foot syndrome with favourable and unfavourable outcomes., Material and Methods: A clinical prospective observational study of the treatment outcomes of fifty-three patients with diabetic foot ulcers hospitalized twice in one specialized centre over the course of the year was conducted. The analysis of histological and immunohistochemical data of the tissues of the edges and the centre of the ulcer taken during the primary surgical treatment was performed. While performing histological analyses of wound tissues, special attention was given to the determination of cellular characteristics of leukocyte-necrotic masses, granulation tissue, and loose and dense connective tissue. Immunohistochemistry was performed using a set of monoclonal antibodies, allowing verification of neutrophilic leukocytes, fibroblasts, and endothelial cells., Results: Unfavourable outcomes (amputation, reamputation, death from cardiovascular diseases, nonhealing ulcer within a year) were registered in 52.8% of cases. Uniform distribution of neutrophils and endothelial cell fibroblasts in all parts of the wound was recorded in patients with a favourable outcome. An unfavourable outcome was predetermined by the uneven content of these cells with a significant increase in neutrophilic leukocytosis in the bottom of the wounds, as well as a significant decrease in the number of fibroblasts and endotheliocytes in the centre of the wounds., Conclusions: The datasets obtained during primary surgical treatment are extremely informative to predict the outcome of the treatment of diabetic foot ulcers and indicate more active surgical strategies with the potential to reduce the treatment time, increase its effectiveness, and eventually make the treatment cost-effective.

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (M pro ) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than -8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of -10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (-10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski's rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.

For many years, the primary focus has been on finding effective treatments for Alzheimer's disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant species Areca Catechu L. (AC) was selected based on the traditional uses against CNS-related diseases. AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15-20 nm, according to SEM analysis. The TEM and SAED pictures also revealed the form and size of AC-HAp-NPs. In vitro anti-acetylcholinesterase and butyrylcholinesterase (AChE and BChE) activities of hydroxyapatite nanoparticles produced from an AC leaf extract was tested in this study. When compared to control, AC-HAp-NPs had higher anti-AChE and BChE activity. The anti-acetylcholinesterase action of phytoconstituents generated from AC leaf extract was mediated by 4AQD and 4EY7, according to a mechanistic study conducted utilizing in silico research. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H 2 O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. The CDFT experiments are supplemented by the calculation of several useful calculated pharmacokinetics indices, their expected biological targets connected to the bioavailability of the five ligands in order to further the goal of studying their bioactivity., Competing Interests: Author SE was employed by Egyptian Organization for Biological Products and Vaccines (VACSERA Holding Company). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pradeep, Prabhuswaminath, Reddy, Srinivasa, Shati, Alfaifi, Eldin I. Elbehairi, Achar, Silina, Stupin, Manturova, Glossman-Mitnik, Shivamallu and Kollur.)

Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide., Competing Interests: The authors have declared that no competing interests exist.

Herein we describe the synthesis of a series of nickel(II) complexes (C1-C3) with Schiff bases (HL1-HL3) derived from 4-amino-5-mercapto-3-methyl-1,2,4-triazole and ortho/meta/para-nitrobenzaldehyde having composition [Ni(L) 2 (H 2 O) 2 ]. The obtained ligands and their complexes were characterized using physico-chemical techniques viz., elemental analysis, magnetic moment study, spectral (electronic, FT-IR, 1H-NMR) and thermal analysis. The elemental analysis and spectral analysis revealed that Schiff bases behave as monoanionic bidentate ligands towards the Ni(II) ion. Whereas, the magnetic moment study suggested the octahedral geometry of all the Ni(II) complexes. The thermal behavior of the complexes has been studied by thermogravimetric analysis and agrees well with the composition of complexes. Further, the biological activities such as antimicrobial and antifungal studies of the Schiff bases and Ni(II) complexes have been screened against bacterial species ( Staphylococcus aureus and Pseudomonas aeruginosa ) and fungal species ( Aspergillus niger and Candida albicans ) activity by MIC method, the results of which revealed that metal complexes exhibited significant antimicrobial activities than their respective ligands against the tested microbial species. Furthermore, the molecular docking technique was employed to investigate the active sites of the selected protein, which indeed helped us to screen the potential anticancer agents among the synthesized ligand and complexes. Further, these compounds have been screened for their in vitro anticancer activity using OVCAR-3 cell line. The results revealed that the complexes are more active than the ligands.

Background: Japanese encephalitis (JE) is a viral zoonotic disease that has been found in several countries of Asia and is responsible for high mortality and morbidity of men and animals in rural and sub-urban endemic areas due to the virus re-circulation among diverse hosts and vectors. The present study estimates the prevalence of the JE virus in the vector and animal population of the Asian continent using a systematic review and meta-analysis., Methods: The Cochran collaborators' Preferred Reporting Items for Systematic Reviews and Meta-Analysis [PRISMA] guidelines were used for systematic review and meta-analysis. The heterogeneity was observed in meta-regression analysis due to several factors including region, species, and different diagnostic assays used in various studies. Thus we did sensitivity and subgroup analysis., Results: The prevalence of the JE virus was calculated using a total sample size of 47,391. Subgroup analysis revealed the JE virus prevalence of 39% in the Southeast Asia region, followed by East Asia with 35% and South Asia with 15% prevalence. Hence, the overall pooled prevalence of the JE virus was 26% in the Asian continent., Conclusions: The highest proportion of infection was found in pigs amongst all animals, reinforcing the fact that they can be used as sentinels to predict outbreaks in humans. The findings of this study will enable researchers and policymakers in better understanding the disease's spatial and temporal distribution, as well as in creating and implementing location-specific JE prevention and control measures., Competing Interests: Competing interests Authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The healing of wounds is a dynamic function that necessitates coordination among multiple cell types and an optimal extracellular milieu. Much of the research focused on finding new techniques to improve and manage dermal injuries, chronic injuries, burn injuries, and sepsis, which are frequent medical concerns. A new research strategy involves developing multifunctional dressings to aid innate healing and combat numerous issues that trouble incompletely healed injuries, such as extreme inflammation, ischemic damage, scarring, and wound infection. Natural origin-based compounds offer distinct characteristics, such as excellent biocompatibility, cost-effectiveness, and low toxicity. Researchers have developed biopolymer-based wound dressings with drugs, biomacromolecules, and cells that are cytocompatible, hemostatic, initiate skin rejuvenation and rapid healing, and possess anti-inflammatory and antimicrobial activity. The main goal would be to mimic characteristics of fetal tissue regeneration in the adult healing phase, including complete hair and glandular restoration without delay or scarring. Emerging treatments based on biomaterials, nanoparticles, and biomimetic proteases have the keys to improving wound care and will be a vital addition to the therapeutic toolkit for slow-healing wounds. This study focuses on recent discoveries of several dressings that have undergone extensive pre-clinical development or are now undergoing fundamental research.

Peptides are currently the most promising lead molecules. Quorum sensing peptides have a variety of structural features and are regularly exposed to post-translational modifications. Antiparkinsonian drugs lose their efficacy after a long period of use, and patients develop motor problems such as drug-induced dyskinesia (DIDs). The interaction between PDE10A and cAMP is necessary for dopamine neurotransmission and may play a role in Parkinson's disease pathogenesis. cAMP and cGMP are cyclic nucleotides that act as secondary messengers in the signal transduction pathway, influencing a range of CNS activities. PDE enzymes hydrolyze phosphodiester bonds to break down cAMP and cGMP, allowing them to control intracellular levels of these second messengers effectively. PDE expression, and hence cyclic nucleotide levels and their downstream targets, may change with age and in numerous age-related illnesses, including Parkinson's disease, according to mounting evidence. At the peak of dyskinesias, cyclic nucleotide levels were lower, and using phosphodiesterase inhibitors before antiparkinsonian medicines reduced the severity of dyskinesias. In a recent study, PapRIV was found to have the ability to activate BV-2 microglia cells, indicating that this quorum sensing peptide may play a role in gut-brain contact. As a result of the current in silico work, mainly focused on QSPs as a lead molecule for inhibiting PDE10A, the SRNAT QSP sequence has been a potent molecule in molecular docking and molecular dynamics simulations. Furthermore, we can test the efficiency of therapeutic components in vitro and in vivo utilizing this computational approach against PDE10A., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Polycyclic aromatic hydrocarbons (PAHs) constitute a group of chemicals with an omnipresence in the environment and our surroundings. With their genotoxicity and carcinogenic nature, it has been proven to be monstrous in our daily life and, especially for pregnant women and their newborn., Aim: This questionnaire study was done to verify the influence of domestic exposure to polyaromatic hydrocarbons on women's periconceptional stage and risk of oral cleft in offspring in the suburban and the rural population of Mysore., Methodology: Two hundred pregnant women as patients from four different hospitals in Mysore were given a questionnaire to be filled with 24 parameters ranging from the knowledge to various means of exposure to the pregnant women with the PAH and the severity and the extent of the orofacial defect in the newborn., Results: It was determined that exposure of pregnant women to the smoke emanating from the method of cooking or heating to smoking (first or passive) and the direct inhalation of gas had the maximum effects on the association of cleft palate (60.7%) in unilateral followed by 90.9% in bilateral, 65.0% in soft tissue, and 76.2% in hard tissue cleft palate., Conclusion: The deleterious effects of the cooking and water heating measures practiced in the suburban and the rural population predisposed the pregnant women to significantly higher chances of offspring with the varied extent of the orofacial defect. There is an influence of domestic exposure to polycyclic aromatic hydrocarbons on women's periconceptional stage and risk of oral cleft in offspring., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Pharmacy and Bioallied Sciences.)

Background and Aim: Pestivirus , a genus of the Flaviviridae family, comprises viruses that affect bovines, sheep, and pigs. Symptoms, including hemorrhagic syndromes, abortion, respiratory complications, and deadly mucosal diseases, are produced in infected animals, which cause huge economic losses to the farmers. Bovine viral diarrhea virus-1, bovine viral diarrhea virus-2, classical swine fever virus, border disease virus, Bungowannah, Hobi-like, and atypical porcine pestivirus belonging to the Pestivirus genus were selected for the study. This study aimed to estimate the codon usage bias and the rate of evolution using the glycoprotein E2 gene. Furthermore, codon usage bias analysis was performed using publicly available nucleotide sequences of the E2 gene of all seven Pestiviruses . These nucleotide sequences might elucidate the disease epidemiology and facilitate the development of designing better vaccines., Materials and Methods: Coding sequences of the E2 gene of Pestiviruses A (n = 89), B (n = 60), C (n = 75), D (n = 10), F (n = 07), H (n = 52), and K (n = 85) were included in this study. They were analyzed using different methods to estimate the codon usage bias and evolution. In addition, the maximum likelihood and Bayesian methodologies were employed to analyze a molecular dataset of seven Pestivirus es using a complete E2 gene region., Results: The combined analysis of codon usage bias and evolutionary rate analysis revealed that the Pestivirus es A, B, C, D, F, H , and K have a codon usage bias in which mutation and natural selection have played vital roles. Furthermore, while the effective number of codons values revealed a moderate bias, neutrality plots indicated the natural selection in A, B, F , and H Pestivirus es and mutational pressure in C, D , and K Pestivirus es. The correspondence analysis revealed that axis-1 significantly contributes to the synonymous codon usage pattern. In this study, the evolutionary rate of Pestiviruses B , H , and K was very high. The most recent common ancestors of all Pestivirus lineages are 1997, 1975, 1946, 1990, 2004, 1990, and 1990 for Pestiviruses A, B, C, D, F, H , and K , respectively. This study confirms that both mutational pressure and natural selection have played a significant role in codon usage bias and evolutionary studies., Conclusion: This study provides insight into the codon usage bias and evolutionary lineages of pestiviruses . It is arguably the first report of such kind. The information provided by the study can be further used to elucidate the respective host adaptation strategies of the viruses. In turn, this information helps study the epidemiology and control methods of pestiviruses ., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Shueb, et al.)

Mitochondria are an autonomous organelle that plays a crucial role in the metabolic aspects of a cell. Cortical spreading depression (CSD) and fluctuations in the cerebral blood flow have for long been mechanisms underlying migraine. It is a neurovascular disorder with a unilateral manifestation of disturbing, throbbing and pulsating head pain. Migraine affects 2.6% and 21.7% of the general population and is the major cause of partial disability in the age group 15-49. Higher mutation rates, imbalance in concentration of physiologically relevant molecules and oxidative stress biomarkers have been the main themes of discussion in determining the role of mitochondrial disability in migraine. The correlation of migraine with other disorders like hemiplegic migraine; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes [MELAS]; tension-type headache (TTH); cyclic vomiting syndrome (CVS), ischaemic stroke; and hypertension has helped in the assessment of the physiological and morphogenetic basis of migraine. Here, we have reviewed the different nuances of mitochondrial dysfunction and migraine. The different mtDNA polymorphisms that can affect the generation and transmission of nerve impulse has been highlighted and supported with research findings. In addition to this, the genetic basis of migraine pathogenesis as a consequence of mutations in nuclear DNA that can, in turn, affect the synthesis of defective mitochondrial proteins is discussed along with a brief overview of epigenetic profile. This review gives an overview of the pathophysiology of migraine and explores mitochondrial dysfunction as a potential underlying mechanism. Also, therapeutic supplements for managing migraine have been discussed at different junctures in this paper., (© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Fermented foods are sources of functionally salient microbes. These microbes when ingested can regulate biomolecule metabolism which has a plethora of health benefits. Lactic acid bacteria species (LABs) isolated from fermented beetroot were biochemically characterized and validated using 16s rRNA sequence. Also, an in vitro assay was conducted to confirm the probiotic activity of the isolates. The cell-free supernatant (CS), cell-free extract (CE), and intact cell (IC) were evaluated for α-glucosidase and α-amylase inhibition. The six isolates RAMULAB01-06 were categorized to be Lactobacillus spp. by observing phenotypic and biochemical characters. Molecular validation using 16S rDNA sequencing, followed by homology search in NCBI database, suggested that the isolates are >95% similar to L. paracasei and L. casei . Also, isolates exhibited probiotic potential with a high survival rate (>96%) in the gastrointestinal condition, and adherence capability (>53%), colonization (>86%), antibacterial, and antibiotic activity. The safety assessments expressed that the isolates are safe. The α-glucosidase and α-amylase inhibition by CS, CE, and IC ranged from 3.97 ± 1.42% to 53.91 ± 3.11% and 5.1 ± 0.08% to 57.15 ± 0.56%, respectively. Hence, these species have exceptional antidiabetic potential which could be explicated to its use as a functional food and health-related food products., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kumari, Huligere, Ramu, Naik Bajpe, Sreenivasa, Silina, Stupin and Achar.)

Cancer is one of the leading causes of death worldwide, accountable for a total of 10 million deaths in the year 2020, according to GLOBOCAN 2020. The advancements in the field of cancer research indicate the need for direction towards the development of new drug candidates that are instrumental in a tumour-specific action. The pool of natural compounds proves to be a promising avenue for the discovery of groundbreaking cancer therapeutics. Elaeocarpus ganitrus (Rudraksha) is known to possess antioxidant properties and after a thorough review of literature, it was speculated to possess significant biomedical potential. Green synthesis of nanoparticles is an environmentally friendly approach intended to eliminate toxic waste and reduce energy consumption. This approach was reported for the synthesis of silver nanoparticles from two different solvent extracts: aqueous and methanolic. These were characterized by biophysical and spectroscopic techniques, namely, UV-Visible Spectroscopy, FTIR, XRD, EDX, DLS, SEM, and GC-MS. The results showed that the nanoconjugates were spherical in geometry. Further, the assessment of antibacterial, antifungal, and antiproliferative activities was conducted which yielded results that were qualitatively positive at the nanoscale. The nanoconjugates were also evaluated for their anticancer properties using a standard MTT Assay. The interactions between the phytochemicals (ligands) and selected cancer receptors were also visualized in silico using the PyRx tool for molecular docking.

The most commonly accepted hypothesis of Alzheimer's disease (AD) is the amyloid hypothesis caused due to formation of accumulation of Aβ42 isoform, which leads to neurodegeneration. In this regard, presenilin-1 (PSEN-1) and -2 (PSEN-2) proteins play a crucial role by altering the amyloid precursor protein (APP) metabolism, affecting γ-secretase protease secretion, finally leading to the increased levels of Aβ. In the absence of reported commercial pharmacotherapeutic agents targeting presenilins, we aim to propose benzophenone integrated derivatives (BIDs) as the potential inhibitors of presenilin proteins through in silico approach. The study evaluates the interaction of BIDs through molecular docking simulations, molecular dynamics simulations, and binding free energy calculations. This is the first ever computational approach to discover the potential inhibitors of presenilin proteins. It also comprises druglikeliness and pharmacotherapeutic potential analysis of the compounds. Out of all the screened BIDs, BID-16 was found to be the lead compound against both the presenilin proteins. Based on these results, one can evaluate BID-16 as an anti-Alzheimer's potential specifically targeting presenilin proteins in near future using in vitro and in vivo methods., Competing Interests: The authors declare no conflict of interest.

Background and Aim: Two endemic capripox infectious diseases, sheeppox (SP) and goatpox (GP) are common in Asia, Africa, and the Middle East. Sheep and goats, in general, are considered current assets of small and marginal farmers and have significant economic value in terms of meat, wool, and skin/hide production. Sheep and goat populations in India total 148.88 million and 74.26 million, respectively. Capripox caused US$ 2.3 million (Indian Rupee [INR] 105 million) in economic damages in Maharashtra (India) alone, and it took over 6 years for a flock to recover from the outbreak. The projected yearly loss at the national level is US$ 27.47 million (INR 1250 million). As a result, Capripox diseases put small and marginal farmers under much financial strain. The present study estimates the seroprevalence of SP and GP diseases in the Asian and African continents using systematic review and meta-analysis. The results of the study will help researchers and policymakers to understand the spatial and temporal distribution of the disease and its burden. In addition, the results are also helpful to design and implement location-specific prevention and eradication measures against these diseases., Materials and Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines of Cochran collaborations were used for systematic review and subsequently meta-analysis were used. The literature was collected from various databases. Initial search string resulted in more than nine thousand articles for the period 2000 to 2020 using the different combinations of keywords and Boolean operators (or not) asterisk* and quotation marks. Out of 9398 papers, 80 studies were chosen for complete test reviews and quality bias evaluation using the inclusion and exclusion criteria. Finally, 21 articles were used for the meta-analysis. The statistical study employed fixed effects and random effects models using R., Results: Seroprevalence of SP and GP was calculated using studies with a cumulative sample size of 4352, out of which sheep and goats' samples together contribute 48%, followed by sheep (32%) and goat (21%). The result of the meta-regression revealed that detection techniques had a significant impact on the overall effect size at 5% level (Qm=14.12). Subgroup analysis of polymerase chain reaction (PCR) test with samples was further grouped into two categories based on the median, and it revealed that 62% of samples used PCR as a detecting test followed by group-II., Conclusion: From the study, it is concluded that SP and GP diseases are highly prevalent; hence, effective vaccines, proper education to farmers through extension activity, and transboundary disease movement restriction are necessary for the control and eradication of the disease., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Suresh, et al.)

The aim of this study was to assess the patterns and pattern disruptions of free radical processes in patients with obstructive jaundice of various origins, and the severity of jaundice before and after decompression. Oxidative stress markers were determined in 128 patients with obstructive jaundice with a tumor genesis (23.4%) or non-tumor genesis (76.6%). The patients were hospitalized at different stages of clinical signs of jaundice. We studied the anti-peroxide activity in plasma, basal and stimulated indicators of the chemiluminescence intensity in leukocytes, leukocyte activity coefficients reflecting the level of reactive oxygen species generated by leukocytes, malondialdehyde levels indicative of the degree of lipid peroxidation and cellular destruction, liver enzymes (markers of cytolysis) and bilirubin levels. Data for hepatocyte death and markers of oxidative stress correlated with the severity of jaundice, its duration and the method of its surgical correction. It is proposed that using markers of free radical processes to assess the prognosis and effectiveness of treatment and to personalize treatment measures will improve the results of jaundice treatment.

Background: Mimusops elengi, popularly known as Bakula in Ayurvedic Medicine, is a member of the Sapotaceae family. Concerning the traditional and Ayurvedic medicinal use of Mimusops elengi leaves, especially in wound healing and oral care, the plausible presence of proteolytic activity in an aqueous Mimusops elengi leaf extract was investigated in our study., Methods: Mimusops elengi Gelatinolytic Protease was named after fractioning the extract. The Zymogram assay validated the gelatin specificity. The effect of MEGP on the wound healing process was investigated using a different assay., Results: The presence of protease with gelatinolytic & caseinolytic activity at 62.53±1.43 U/h and 15.31±0.64 U/h, respectively. The aqueous enzyme fraction was named Mimusops elengi Gelatinolytic Protease (MEGP). The specificity of gelatin was confirmed by zymogram. Gelatinolytic activity of MEGP was also higher than that of trypsin at 27.96±0.38 U/h. MEGP was 49.14±1.61 % inhibited by PMSF, indicating the predominant presence of serine proteases. The optimal pH and temperature for MEGP were found to be 8 and 37°C, implying that it is an alkaline protease. MEGP dissolved the blood clot at a rate of 8.41±1.04 U/h, which is higher than the trypsin clot-dissolving rate of 1.027±0.04 U/h. The plasma clot hydrolytic capacity is confirmed when MEGP hydrolyzes alpha-polymer subunits in a dose-dependent manner., Conclusion: This investigation shows that MEGP has a plasmin-like activity that possesses a significant role in clot disintegration and other wound ailments, warranting its use in traditional Indian medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of -8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.

Non-small cell lung cancer (NSCLC) is a prominent subtype of lung carcinoma that accounts for the majority of cancer-related deaths globally, and it is responsible for about 80% to 85% of lung cancers. Mitogen-Activated Protein Kinase (MAPK) signaling pathways are a vital aspect of NSCLC, and have aided in the advancement of therapies for this carcinoma. Targeting the Ras/Raf/MEK/ERK pathway is a promising and alternative method in NSCLC treatment, which is highlighted in this review. The introduction of targeted medicines has revolutionized the treatment of patients with this carcinoma. When combined with current systems biology-driven stratagems, repurposing non-cancer drugs into new therapeutic niches presents a cost-effective and efficient technique with enhancing outcomes for discovering novel pharmacological activity. This article highlights the successful cutting-edge techniques while focusing on NSCLC targeted therapies. The ultimate challenge will be integrating these repurposed drugs into the therapeutic regimen of patients affected with NSCLC to potentially increase lung cancer cure rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jain, Prasad, Pradeep, Dharmashekar, Achar, Ekaterina, Victor, Amachawadi, Prasad, Pruthvish, Syed, Shivamallu and Kollur.)

Venom peptides have been evolving complex therapeutic interventions that potently and selectively modulate a range of targets such as ion channels, receptors, and signaling pathways of physiological processes making it potential therapeutic. Several venom peptides were deduced in vivo for clinical development targeting pain management, diabetes, cardiovascular diseases, antimicrobial activity. Several contributions have been detailed for a clear perspective for a better understanding of venomous animals, their venom, and their pharmacological effects. Here we unravel and summarize the recent advances in wide venom peptides across varieties of species for their therapeutics prospects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Upon examination of the fruit extract of Cucumis sativus L. for its pharmacological benefits, it was previously observed that it has potential proteolytic, fibrinogenolytic and procoagulant activities. These properties can be attributed to the presence of the protease. In this regard, the present study comprised of purification and characterization of protease. Purification of the enzyme involved ammonium sulfate precipitation followed by gel filtration and ion exchange chromatography. The purified cucumis protease (CPro) exhibits homogeneity as attested by SDS-PAGE and RP-HPLC with a retention time of 14.246 min with molecular mass ~75.3 kDa. CPro was identified as a glycoprotein and serine protease. Azocasein is the preferred substrate for CPro as it showed low K m value of 0.3809 mg/ml. Purified CPro exhibits optimum activity at 37 °C and pH 8. CPro shows its involvement in hemostasis-the very first step in wound healing. CPro degrades the subunits of human fibrinogen in the order Aα > Bβ > γ. It also hydrolyzes the subunits of the partially cross-linked fibrin clot in the order α-polymer > γ-γ dimer > β-chain. CPro reduced the clotting time of citrated plasma, prothrombin time and activated partial thromboplastin time of plasma. CPro is neither hemorrhagic nor edema-inducing, thus considered to be a non-toxic protease. This work provides evidence for the use of cucumber extract in wound healing and authenticates its use in cosmetics.

Caralluma umbellata peroxidase (CUP) is an acidic heme-containing protein having a molecular weight of ~42 kDa and is specific to guaiacol. It is not a glycoprotein. It was purified to 12.5-fold purity with 6.16 % yield. Its activity is dependent on hydrogen peroxide and has an optimum pH and temperature of 6.2 and 45 °C respectively. It can decolorize dyes, viz., Aniline Blue, Reactive Black 5, and Reactive Blue 19 but not Congo Red, while HRP can decolorize Congo Red also. It has lignin-degrading potentiality as it can decompose veratryl alcohol. Detoxification of phenol was more by CUP compared to HRP while with p-nitrophenol HRP has a greater detoxification rate. Based on our results, CUP was identified to be capable of oxidizing a variety of hazardous substances and also a lignin-degrading plant biocatalyst.

Condensed-bicyclic 4,6-substituted1,2,4-triazolo-1,3,4-thiadiazole derivatives (CBTT) have been shown to possess a wide spectrum of pharmacological activities. In this study, several novel CBTT derivatives were synthesized and investigated for their possible role as anti-neoplastic agents. The anti-proliferative effect of various CBTT derivatives was analyzed against tumor cell lines by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. One of the potential CBTT derivative, 5-(3-(2,3-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)flurobenzonitrile (DTTF) was found to be the most potent against cervical cancer SiHa cells and exhibited minimal effect against normal cells. Molecular docking analysis indicated that transcription factor NF-κB was one of the potential molecular targets modulated by DTTF. Specifically, the drug blocked the TNFα-induced phosphorylation of upstream IκBα kinase in a time-dependent manner leading to the suppression of NF-κB activation and nuclear translocation. DTTF also potentiated the apoptotic effect of TNFα, as well as significantly inhibited migration and invasion of tumor cells. Overall, these findings indicate a potential novel role and mechanism(s) of action of DTTF as an anticancer agent against diverse malignancies.

A new simple, rapid and precise RP-HPLC method was developed for the extraction and quantitative estimation of caffeine (C), (-)-epigallocatechin gallate (EGCG), (+)-catechin(Ct), (-)-epicatechin(EC), and (-)-epicatechin gallate (ECG) (collectively named as Tea Powder Bioactives TPBAs) extracted from tea powder using different ratios of ethanol: water. The simultaneous determination of TPBAs was performed using the UV spectrophotometric method which employs the absorbance at 205 nm (λmax of caffeine and polyphenols). This method is a gradient based HPLC method with a flow rate of 0.8 mL/min using Inertsil ODS 100 × 4.6 mm, 3 μm column with methanol and ammonium dihydrogen phosphate (pH-2.8) as mobile phase. The method was validated in terms of specificity, precision, linearity, accuracy, limit of quantification (LOQ), and limit of detection (LOD). The linearity of the proposed method was investigated for concentration ranging between 0.5-60 μg/mL with regression co-efficient, R(2) = 0.999-1.0. This method estimates all the TPBAs simultaneously with enhanced precision and linearity as per the ICH guidelines. Also, to confirm the individual TPBA, the antioxidant property of the each TPBA was analyzed which was commensurate with that of the previous reports.

Background: Kollamalayaali tribes of South India use latex of Maclura spinosa for milk curdling. This action is implicated to proteases which exhibit strong pharmacological potential in retardation of blood flow and acceleration of wound healing., Objective: To validate the presence of a proteolytic enzyme(s) in Maclura spinosa latex (MSL), and to investigate their probable role in hemostasis., Materials and Methods: Processed latex was examined for proteolytic and hemostatic activity using casein and human fibrinogen as substrates, respectively. Caseinoltyic activity was compared with two standard proteases viz., trypsin I and trypsin II. Effect of various standard protease inhibitors viz., iodoacetic acid (IAA), phenylmethylsulfonyl fluoride (PMSF), ethylene glycol tetraacetic acid, and ethylenediaminetetraacetic acid on both caseinolytic and fibrinogenolytic activities were examined. Electrophoretogram of fibrinogenolytic assays were subjected to densitometric analysis., Results: Proteolytic action of MSL was found to be highly efficient over trypsin I and trypsin II in dose-dependent caseinolytic activity (P < 0.05; specific activity of 1,080 units/mg protein). The Aα and Bβ bands of human fibrinogen were readily cleaved by MSL (for 1 μg crude protein and 30 min of incubation time). Furthermore, MSL cleaved γ subunit in dose- and time-dependent manner. Quantitative correlation of these results was obtained by densitometric analysis. The caseinolytic activity of MSL was inhibited by IAA, PMSF. While, only PMSF inhibited fibrinogenolytic activity., Conclusions: MSL contains proteolytic enzymes belonging to two distinct superfamilies viz., serine protease and cysteine proteases. The fibrinogenolytic activity of MSL is restricted to serine proteases only. The study extrapolates the use of M. spinosa latex from milk curdling to hemostasis., Summary: Proteolytic enzymes present in latex of Maclura spinosa can be assigned to two different protease superfamilies viz., serine protease and cysteine protease as revealed by the inhibitory studies of caseinolytic activity. Among them, only serine protease can be considered as hemostatically significant as inhibition of fibrinogenolytic action of Maclura spinosa latex protease is shown only by PMSF, a serine protease-specific inhibitor. Abbreviations used: MSL: Maclura spinos Latex, IAA: Iodo Acetic Acid, EDTA: Ethylene Diamine Tetra Acetic Acid, EGTA: Ethylene glycol tetra acetic acid, PMSF: Phenyl methyl sulphonyl fluoride.

Vast applications of peroxidases create an increasing demand to characterize peroxidases from new sources with more applicability potential. The aim of the present study was to check the presence of peroxidase activity from Caralluma umbellata. This is the first report on the C. umbellata peroxidase (CUP). The presence of peroxidase was revealed by the histochemical analysis of the stem sections, zymographic studies, and in vitro peroxidase activity assay using various reducing substrates viz., 2, 2'-azinobis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), guaiacol, o-dianisidine, and ferulic acid. The band pattern in zymogram confirms that CUP has a molecular weight less than that of horseradish peroxidase (44 kDa). Comparative evaluation of peroxidase activity of CUP with respect to horseradish peroxidase (HRP) indicates that CUP catalyzes ABTS and ferulic acid in a similar pattern as HRP but with guaiacol, the extent of catalysis shown by CUP over HRP is high. The standard inhibitors sodium azide and sodium meta bisulphite inhibited CUP activity in a dose dependent manner.