Antiangiogenic activity of zinc and zinc-sorafenib combination using the chick chorioallantoic membrane assay: a descriptive study

Background: Zinc, a trace element, is known for downregulating several proangiogenic growth factors and cytokines. However, its antiangiogenic activity is not adequately studied. The present study was aimed to evaluate the possible antiangiogenic activity of zinc via the chick chorioallantoic membrane (CAM) assay. Also, the antiangiogenic activity of the combination therapy of zinc with various doses of sorafenib, a tyrosine kinase inhibitor, was evaluated.Methods: A pilot study was initially conducted so as to select suitable doses of zinc and sorafenib. The antiangiogenic activity after combining zinc 2.5 μg/embryo with sorafenib 1, and 2 μg/embryo was also evaluated. The antiangiogenic activity was quantified in terms of total length of blood vessels, number of junctions, number of branching points, and mean length of the blood vessels.Results: Zinc 2.5 μg/embryo showed significant (p 0.05) to that of sorafenib 2 μg/embryo.Conclusions: Zinc caused significant antiangiogenic activity in the CAM assay. The lack of addition/synergism in the zinc-sorafenib combination could have been due to the variability in the dose/ratio selection. Addition of zinc to sorafenib therapy could improve treatment tolerability, reduce cost of therapy, and reduce the emergence of drug resistance. Future mechanistic studies could identify the exact pharmacodynamics of zinc as an angiogenesis inhibitor

COVID-19 PANDEMIC: A SYSTEMATIC REVIEW ON THE CORONAVIRUSES OF ANIMALS AND SARS-CoV-2

Coronaviruses (CoVs), classified into four genera, viz., alpha-, beta-, gamma-, and Delta- CoV, represent an important group of diverse transboundary pathogens that can infect a variety of mammalian and avian species including humans, animals, poultry, and non-poultry birds. CoVs primarily infect lung and gut epithelial cells, besides monocytes and macrophages. CoVs have high mutation rates causing changes in host specificity, tissue tropism, and mode of virus excretion and transmissions. The recent CoV zoonoses are SARS, MERS, and COVID-19 that are caused by the transmission of beta-CoVs of bats to humans.  Recently, reverse zoonoses of the COVID-19 virus have been detected in dogs, tigers, and minks. Beta-CoV strains also infect bovine (BCoV) and canine species (CRCoV); both these beta-CoVs might have originated from a common ancestor. Despite the high genetic similarity between BCoV, CRCoV, and HCoV-OC43, these differ in species specificity. Alpha-CoV strains infect canine (CCoV), feline (FIPV), swine (TGEV and PEDV), and humans (HCoV229E and NL63). Six coronavirus species are known to infect and cause disease in pigs, seven in human beings, and two in dogs. The high mutation rate in CoVs is attributed to error-prone 3′-5′ exoribonuclease (NSP 14), and genetic recombination to template shift by the polymerase. The present compilation describes the important features of the CoVs and diseases caused in humans, animals, and birds that are essential in surveillance of diverse pool of CoVs circulating in nature, and monitoring interspecies transmission, zoonoses, and reverse zoonoses

Exploration of Anti-HIV Phytocompounds against SARS-CoV-2 Main Protease: Structure-Based Screening, Molecular Simulation, ADME Analysis and Conceptual DFT Studies

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 (Mpro) (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.Fil: Murali, Mahadevamurthy. University Of Mysore; IndiaFil: Gowtham, Hittanahallikoppal Gajendramurthy. Nrupathunga University; IndiaFil: Shilpa, Natarajamurthy. University Of Mysore; IndiaFil: Krishnappa, Hemanth Kumar Naguvanahalli. University Of Mysore; IndiaFil: Ledesma, Ana Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Centro de Investigación en Biofísica Aplicada y Alimentos. - Universidad Nacional de Santiago del Estero. Centro de Investigación en Biofísica Aplicada y Alimentos; ArgentinaFil: Jain, Anisha S.. University Of Mysore; IndiaFil: Shati, Ali A.. King Khalid University; Arabia SauditaFil: Alfaifi, Mohammad Y.. Vacsera Holding Company; EgiptoFil: Elbehairi, Serag Eldin I.. Jss Academy Of Higher Education And Research; IndiaFil: Achar, Raghu Ram. Pirogov Russian National Research Medical University; RusiaFil: Silina, Ekaterina. Universitat de Les Illesbalears; EspañaFil: Stupin, Victor. Centro de Investigaciónen Materiales Avanzados; MéxicoFil: Ortega Castro, Joaquín. Jss Academy Of Higher Education And Research; IndiaFil: Frau, Juan. Universitat de Les Illesbalears; EspañaFil: Flores Holguín, Norma. Centro de Investigaciónen Materiales Avanzados; MéxicoFil: Amruthesh, Kestur Nagaraj. University Of Mysore; IndiaFil: Shivamallu, Chandan. Jss Academy Of Higher Education And Research; IndiaFil: Kollur, Shiva Prasad. University Of Mysore; IndiaFil: Glossman Mitnik, Daniel. Centro de Investigaciónen Materiales Avanzados; Méxic

Evaluating the Antimicrobial and Anti-Hemolytic Activity of Synthesized Pseudopeptide against <i>Leptospiral</i> Species: In Silico and In Vitro Approach

Bacterial infections are one of the leading causes of morbidity, mortality, and healthcare complications in patients. Leptospirosis is found to be the most prevalent, re-emergent, and neglected tropical zoonotic disease worldwide. The adaptation to various environmental conditions has made Leptospira acquire a large genome (~4.6 Mb) and a complex outer membrane, making it unique among bacteria that mimic the symptoms of jaundice and hemorrhage. Sph2 is another important virulence factor that enhances hemolytic sphingomyelinase—capable of moving inside mitochondria—which increases the ROS level and decreases the mitochondrial membrane potential, thereby leading to cell apoptosis. In the present study, 25 suspected bovine serum samples were subjected to the Microscopic Agglutination Test (MAT) across the Mysuru region. Different samples, such as urine, serum, and aborted materials from the confirmed MAT-positive animals, were used for isolation and genomic detection by conventional PCR targeting virulence gene, Lipl32, using specific primers. Further, in vitro and in silico studies were performed on isolated cultures to assess the anti-leptospiral, anti-hemolytic, and sphingomyelinase enzyme inhibition using novel pseudopeptides. The microdilution technique (MDT) and dark field microscope (DFM) assays revealed that at a concentration of 62.5 μg/mL, the pseudopeptide inhibited 100% of the growth of Leptospira spp., suggesting its efficiency in the treatment of leptospirosis. The flow cytometry analyses show the potency of the pseudopeptide against sphingomyelinase enzymes using human umbilical vein endothelial cells (HUVECs). Thus, the present study demonstrated the efficacy of the pseudopeptide in the inhibition of the growth of Leptospira, and therefore, this can be used as an alternative drug for the treatment of leptospirosis

Not Available

Not AvailableThe spike (S) glycoprotein and nucleocapsid (N) proteins are the crucial pathogenic proteins of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus during its interaction with the host. Even FDA-approved drugs like dexamethasone and grazoprevir are not able to curb the viral progression inside the host and are reported with adverse effects on body metabolism. In this context, we aim to report corilagin a novel, potential dual inhibitor of S and N proteins from Terminalia chebula. The bioactive compounds of T. chebula were subjected to a series of computational investigations including molecular docking simulations, molecular dynamics (MD) simulations, binding free energy calculations, and PASS pharmacological analysis. The results obtained from these studies revealed that corilagin was highly interactive with the S (-8.9 kcal/mol) and N (-9.2 kcal/mol) proteins, thereby showing dual inhibition activity. It was also found to be stable enough to induce biological activity inside the inhibitor binding pocket of the target enzymes throughout the dynamics simulation run for 100 ns. This is also confirmed by the changes in the protein conformations, evaluated using free energy landscapes. Outcomes from this investigation identify corilagin as the lead potential dual inhibitor of S and N proteins of SARS-CoV-2, which could be taken for biological studies in near future.Communicated by Ramaswamy H. Sarma.Not Availabl

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London