Carbohydrates and lipids metabolic enzymes inhibitory, antioxidant, antimicrobial and cytotoxic potentials of Anchusa ovata Lehm. from Palestine

Introduction: Throughout history, therapeutically active plant products have received substantial attention due to their valuable role in the discoveries of specific medications. The aim of this study was to assess, for the first time, the antimicrobial, antioxidant, antilipase, anti-α-amylase and cytotoxic properties of four fractions derived from Anchusa ovata Lehm. (AO) leaves. Methods: Antioxidant, antilipase and anti-amylase potentials of (AO) were established using DPPH (1,1-diphenyl- 2-picrylhydrazyl), p-nitrophenyl butyrate and dinitro-salicylic acid procedures, respectively, while antimicrobial activity was conducted using broth microdilution assay against eight Gram-positive, Gram-negative bacterial strains in addition to one fungal strain. Moreover, the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium] cytotoxic assay was utilized against cervical cancer cells (HeLa). Results: The methanol fraction of AO showed potential antioxidant, antilipase, and α-amylase inhibitory activities with IC50 values of 9.55 ± 0.13, 53.7 ± 0.41 and 16.55 ± 1.84 μg/ml, respectively compared with the positive controls Trolox, Orlistat and Acarbose that had IC50 values of 3.23 ± 0.92, 12.3 ± 0.35 and 28.18 ± 1.22 μg/ml, respectively. Moreover, the hexane, acetone, and methanol fractions had wide ranges of antimicrobial potential. In addition, the cytotoxic activity outcomes which showed the best activity was for the aqueous followed by acetone, hexane and methanol fractions with IC50 values of 1.04, 2.72, 3.96 and 17.67 mg/ ml, respectively. Conclusion: Our data demonstrate a wide range of biological characteristics for each AO plant fraction. This profiling information about the methanol fraction provided important data for further research and pharmaceutical applications.The authors would like to acknowledge the Faculty of Medicine and Health Sciences at An-Najah National University for facilitating the accomplishment of the current study

The role of antibiotic resistance mobile genetic element MCR-1 in enhancing bacterial survival in macrophages

Background: Antimicrobial resistance (AMR) determinants such as mobile colistin resistance (MCR-1) that encodes colistin resistance are increasingly spreading in healthcare-associated and community-acquired infections. 1 Colistin, a cationic peptide antibiotic, resistance is encoded by the MCR-1 gene that functions as phosphoethanolamine (PEA) transferase which adds a PEA moiety to lipid A head group rendering it resistant to host antimicrobial cationic peptides (AMPs). 2,3 The given hypothesis is that MCR-1 harboring bacteria survive longer in macrophages by evading AMPs. This study aims to investigate the role of MCR-1 in enhancing bacterial survival in macrophages. Methods: Eight E. coli strains were used in the study in which 4 strains were MCR-1 positive and 4 strains were negative. MCR-1 was confirmed by Polymerase Chain Reaction (PCR), and colistin and polymyxin minimal inhibitory concentrations (MICs) were determined using the microdilution method. Macrophage bactericidal assay was employed to examine bacterial survival using adherent murine RAW264 macrophages in an in-vitro bacterial infection model. Briefly, Macrophages were infected with E. coli strains at a multiplicity of infection (MOI) of 50 for 1 hour. The survival of bacteria associated with macrophages was quantified by agar plating method to calculate colony forming units (CFU/ml). Cytokines released from infected macrophages were quantified using ELISA method respectively. Results: Colistin MICs for MCR-1 positive E. coli strains were >25 ?g/ml, whereas MCR-1 negative E. coli MICs < 6.2 ?g/ml. E. coli strains encoding MCR-1 survived significantly more in association with macrophages (p = 0.024) compared to MCR-1 negative E. coli strains. Further, E.coli strains encoding MCR-1 induced slightly less IL-1? release from infected macrophages compared to E. coli strains without MCR-1 (p = 0.05). Taken together, the data suggest that MCR-1 enhanced bacterial survival in association with macrophages and modulated innate immune responses which may lead to treatment failure. Conclusion: MCR-1 encoding E. coli strains conferred resistance to colistin and survived more in association with macrophages.Qscienc

COVID-19 Severity in Patients With Apical Periodontitis: A Case Control Study

Objectives: Apical periodontitis (AP) has been associated with systemic inflammatory biomarkers that have also been associated with COVID-19 severity. This study was designed to test the hypothesis that the presence of apical periodontitis could be associated with increased risk of COVID-19 complications. Methods: A case control study (N = 949) was performed using the medical and dental records of patients diagnosed with COVID-19 in the State of Qatar between March 2020 and February 2021. Cases comprised COVID-19 patients (n = 63) who experienced complications (death, intensive care unit admissions, mechanical ventilation), and controls were COVID-19 patients (n = 886) who recovered without such complications. The presence of periapical apical periodontitis was assessed on the radiographic records taken prior to COVID-19 infection. Associations between apical periodontitis and COVID 19 complications were analysed using logistic regression models adjusted for demographic and medical factors. Blood biomarkers were assessed in both groups and compared using the Kruskal-Wallis test. Results: COVID-19 complications were found to be associated with the presence of apical periodontitis (adjusted odds ratio = 2.72; 95% CI, 1.30-5.68; P = .008). Blood analyses revealed that COVID-19 patients with apical periodontitis had higher levels of white blood cells and haemoglobin A1c than the patients without apical periodontitis. Conclusions: The presence of apical periodontitis could be associated with increased risk of COVID-19 complications.The authors acknowledge the support of the Business Intelligence Unit of Hamad Medical Corporation, especially Anvar Hassan and Chris Choda. We also acknowledge the support of Hamad Dental Center, Qatar University College of Dental Medicine, and McGill University Faculty of Dental Medicine and Oral Health Sciences.Scopu

The determination of causality of drug induced liver injury in patients with COVID-19 clinical syndrome

Background Drug induced liver injury (DILI) is a rising morbidity amongst patients with COVID-19 clinical syndrome. The updated RUCAM causality assessment scale is validated for use in the general population, but its utility for causality determination in cohorts of patients with COVID-19 and DILI remains uncertain. Methods This retrospective study was comprised of COVID-19 patients presenting with suspected DILI to the emergency department of Weill Cornell medicine-affiliated Hamad General Hospital, Doha, Qatar. All cases that met the inclusion criteria were comparatively adjudicated by two independent rating pairs (2 clinical pharmacist and 2 physicians) utilizing the updated RUCAM scale to assess the likelihood of DILI. Results A total of 72 patients (mean age 48.96 (SD ± 10.21) years) were examined for the determination of DILI causality. The majority had probability likelihood of “possible” or “probable” by the updated RUCAM scale. Azithromycin was the most commonly reported drug as a cause of DILI. The median R-ratio was 4.74 which correspond to a mixed liver injury phenotype. The overall Krippendorf's kappa was 0.52; with an intraclass correlation coefficient (ICC) of 0.79 (IQR 0.72-0.85). The proportion of exact pairwise agreement and disagreement between the rating pairs were 64.4%, kappa 0.269 (ICC 0.28 [0.18, 0.40]) and kappa 0.45 (ICC 0.43 [0.29-0.57]), respectively. Conclusion In a cohort of patients with COVID-19 clinical syndrome, we found the updated RUCAM scale to be useful in establishing “possible” or “probable” DILI likelihood as evident by the respective kappa values; this results if validated by larger sample sized studies will extend the clinical application of this universal tool for adjudication of DILI