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AbstractA revival interest has been given to natural products as sources of phytocompounds to be used as alternative treatment against infectious diseases. In this context, we aimed to investigate the antimicrobial potential of Ziziphus honey (ZH) against twelve clinical bacterial strains and several yeasts and molds using in vitroand computational approaches. The well-diffusion assay revealed that ZH was able to induce growth inhibition of most Gram-positive and Gram-negative bacteria. The high mean growth inhibition zone (mGIZ) was recorded in E. coli(Clinical strain, 217), S. aureusfollowed by E. coliATCC 10536 (mGIZ values: 41.00 ± 1 mm, 40.67 ± 0.57 mm, and 34.67 ± 0.57 mm, respectively). The minimal bactericidal concentrations (MBCs) and minimal fungicidal concentration values (MFCs) from approximately 266.33 mg/mL to over 532.65 mg/mL. Molecular docking results revealed that the identified compounds maltose, 2-furoic acid, isopropyl ester, 2,4-imidazolidinedione, 5-(2-methylpropyl)-(S)- and 3,4,5-trihydroxytoluene, S-Methyl-L-Cysteine, 2-Furancarboxylic acid, L-Valine-N-ethoxycarbonyl, Hexanoic acid, 3,5,5-trimethyl-, Methyl-beta-D-thiogalactoside, gamma-Sitosterol, d-Mannose, 4-O-Methylmannose, 2,4-Imidazolidinedione, 5-(2-methylpropyl)- (S) were found to have good affinity for targeted receptor, respectively. Through a 100-ns dynamic simulation research, binding interactions and stability between promising phytochemicals and the active residues of the studied enzymes were confirmed. The ADMET profiling of all identified compounds revealed that most of them could be qualified as biologically active with good absorption and permeation. Overall, the results highlighted the efficiency of ZH against the tested clinical pathogenic strains. The antimicrobial potential and the potency displayed by the identified compounds could imply their further pharmacological applications.Communicated by Ramaswamy H. Sarma

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Background Research studies have focused on discovering new anti-proliferative and pro-apoptotic agents derived from natural products from which honey constitutes a prominent candidate. The Acacia honey (AH) is known to display anticancer activity, but the mechanisms of action are still not well defined.Objectives Using in vitroand computational approaches, we aimed to assess the interaction among selected bioactive compounds derived from AH, with the apoptotic protein p53, which could trigger apoptosis.Materials and Methods The phytocompounds of AH were investigated via gas chromatography–mass spectrophotometry analysis. The cytotoxic effect and induced apoptosis on the MCF-7 breast cancer cell line were assessed by 3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide and acridine orange-ethidium bromide staining approaches. The molecular docking analysis between AH compounds and p53 was carried out.Results The drug-likeness prediction revealed that most of the identified compounds meet Lipinski’s rules. We demonstrate that AH exerts an interesting cytotoxic effect in a dose-dependent manner against the MCF-7 cell line with IC505.053µg/mL. Significant cell alterations and notable induced apoptosis were detected when cells were treated with AH. The molecular docking analysis revealed that melezitose is among the most important potential bioactive compounds that interact with p53 leading to apoptosis. The binding affinity was −8.1 kcal/mol, and the closest molecular interactions in the active site included 10 residues, which could explain the potential biological activity.Conclusion This work sheds light on AH as a significant source of bioactive chemicals with potential for promoting apoptosis that may be exploited as an alternative therapy for breast cancer.

AbstractThe spread of new coronavirus infection starting December 2019 as novel SARS-CoV-2, identified as the causing agent of COVID-19, has affected all over the world and been declared as pandemic. Approximately, more than 8,807,398 confirmed cases of COVID-19 infection and 464,483 deaths have been reported globally till the end of 21 June 2020. Until now, there is no specific drug therapy or vaccine available for the treatment of COVID-19. However, some potential antimalarial drugs like hydroxychloroquine and azithromycin, antifilarial drug ivermectin and antiviral drugs have been tested by many research groups worldwide for their possible effect against the COVID-19. Hydroxychloroquine and ivermectin have been identified to act by creating the acidic condition in cells and inhibiting the importin (IMPα/β1) mediated viral import. There is a possibility that some other antimalarial drugs/antibiotics in combination with immunomodulators may help in combatting this pandemic disease. Therefore, this review focuses on the current use of various drugs as single agents (hydroxychloroquine, ivermectin, azithromycin, favipiravir, remdesivir, umifenovir, teicoplanin, nitazoxanide, doxycycline, and dexamethasone) or in combinations with immunomodulators additionally. Furthermore, possible mode of action, efficacy and current stage of clinical trials of various drug combinations against COVID-19 disease has also been discussed in detail.Communicated by Ramaswamy H. Sarma

Malaria represents one of the major life-threatening diseases that poses a huge socio-economic impact, worldwide. Chemoprophylaxis vaccination using a relatively low number of wild-type infectious sporozoites represents an attractive and effective vaccine strategy against malaria. However, the role of immune responses to pre-erythrocytic versus blood-stage parasites in protection against different antimalarial drugs remains unclear. Here, in the present study, we explored the immune responses against the repetitive inoculation of live Plasmodium yoelii (P. yoelii) sporozoites in an experimental Swiss mouse model under antimalarial drug lumefantrine chemoprophylaxis (CPS-LMF). We monitored the liver stage parasitic load, pro/anti-inflammatory cytokines expression, and erythrocytic stage patency, following repetitive cycles of sporozoites inoculations. It was found that repetitive sporozoites inoculation under CPS-LMF results in delayed blood-stage infection during the fourth sporozoites challenge, while sterile protection was produced in mice following the fifth cycle of sporozoites challenge. Intriguingly, we observed a significant up-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α and IL-12) and iNOS response and down-regulation of anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) in the liver HMNC (hepatic mononuclear cells) and spleen cells after 4th and 5th cycle of sporozoites challenge in the CPS-LMF mice. Meanwhile, we also noticed that the liver stage parasites load under CPS-LMF immunization has gradually reduced after 2nd, 3rd, 4th and 5th sporozoites challenge. Overall, our study suggests that chemoprophylaxis vaccination under LMF drug cover develops strong immune responses and confer superior long-lasting protection against P. yoeliisporozoites. Furthermore, this vaccination strategy can be used to study the protective and stage-specific immunity against new protective antigens.

Genetic predisposition has been always noted in the context of familial hematological malignancies. Epidemiological studies have provided evidence consisting of an increased risk to develop blood cancer in relatives diagnosed with the same pathology and characterized by early age at diagnosis and higher severity compared to sporadic forms. With the emergence of new genomic testing approaches, the prevalence of familial aggregations of hematological malignancies seems to be under estimated. The heterogeneity of clinical features explains the wide number of genes’ mutations reported to date and the variable penetrance of variants. Nevertheless, the genetic basis of familial hematological malignancies is still not well understood. Identifying the genetic background in familial aggregations provides a valuable tool for prognostic evaluation, personalized treatment and better genetic counseling in high-risk families. Herein, we provide an overview of genes reported in the last few years in association to hematological malignancies including familial form of Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, acute Myeloid Leukemia and acute Lymphoblastic Leukemia.