Effect of ethnomedicinal plants used in folklore medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>occurs naturally in the human gut; however, certain strains that can cause infections, are becoming resistant to antibiotics. Multidrug-resistant <it>E. coli </it>that produce extended-spectrum β lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of urinary tract infections (UTIs) and bloodstream infections may be associated with these community-onsets. This is the first report testing the antibiotic resistance-modifying activity of nineteen Jordanian plants against multidrug-resistant <it>E. coli</it>.</p> <p>Methods</p> <p>The susceptibility of bacterial isolates to antibiotics was tested by determining their minimum inhibitory concentrations (MICs) using a broth microdilution method. Nineteen Jordanian plant extracts (<it>Capparis spinosa </it>L., <it>Artemisia herba-alba Asso, Echinops polyceras </it>Boiss., <it>Gundelia tournefortii </it>L, <it>Varthemia iphionoides </it>Boiss. & Blanche, <it>Eruca sativa Mill</it>., <it>Euphorbia macroclada </it>L., <it>Hypericum trequetrifolium </it>Turra, <it>Achillea santolina </it>L., <it>Mentha longifolia </it>Host, <it>Origanum syriacum </it>L., <it>Phlomis brachydo</it>(Boiss.) Zohary, <it>Teucrium polium </it>L., <it>Anagyris foetida </it>L., <it>Trigonella foenum-graecum </it>L., <it>Thea sinensis </it>L., <it>Hibiscus sabdariffa </it>L., <it>Lepidium sativum </it>L., <it>Pimpinella anisum </it>L.) were combined with antibiotics, from different classes, and the inhibitory effect of the combinations was estimated.</p> <p>Results</p> <p>Methanolic extracts of the plant materials enhanced the inhibitory effects of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid against both the standard strain and to a lesser extent the resistant strain of <it>E. coli</it>. Two edible plant extracts (<it>Gundelia tournefortii L</it>. and <it>Pimpinella anisum L</it>.) generally enhanced activity against resistant strain. Some of the plant extracts like <it>Origanum syriacum </it>L.(Labiateae), <it>Trigonella foenum- graecum </it>L.(Leguminosae), <it>Euphorbia macroclada </it>(Euphorbiaceae) and <it>Hibiscus sabdariffa </it>(Malvaceae) did not enhance the activity of amoxicillin against both standard and resistant <it>E. coli</it>. On the other hand combinations of amoxicillin with other plant extracts used showed variable effect between standard and resistant strains. Plant extracts like <it>Anagyris foetida </it>(Leguminosae) and <it>Lepidium sativum </it>(Umbelliferae) reduced the activity of amoxicillin against the standard strain but enhanced the activity against resistant strains. Three edible plants; Gundelia <it>tournefortii </it>L. (Compositae) <it>Eruca sativa </it>Mill. (Cruciferae), and <it>Origanum syriacum </it>L. (Labiateae), enhanced activity of clarithromycin against the resistant <it>E. coli </it>strain.</p> <p>Conclusion</p> <p>This study probably suggests possibility of concurrent use of these antibiotics and plant extracts in treating infections caused by <it>E. coli </it>or at least the concomitant administration may not impair the antimicrobial activity of these antibiotics.</p

CD8+ T Cells as a Source of IFN-γ Production in Human Cutaneous Leishmaniasis

Cutaneous leishmaniasis (CL) is usually a self-healing skin lesion caused by different species of Leishmania parasite. Resistance and susceptibility of mice to Leishmania major infection is associated with two types of CD4+ T lymphocytes development: Th1 type response with production of cytokine IFN-γ is associated with resistance, whereas Th2 type response with production of cytokines IL-4 and IL-5 is associated with susceptibility. A clear Th1/Th2 dichotomy similar to murine model is not defined in human leishmaniasis and we need as much information as possible to define marker(s) of protection. We purified CD4+/CD8+ T cells, stimulated them with Leishmania antigens and analysed gene and protein expression of Th1/Th2 cytokines in volunteers with a history of self-healing CL who are presumed to be protected against further Leishmania infection. We have seen significant upregulation of IFN-γ gene expression and high IFN-γ production in the Leishmania stimulated CD4+ T cells and CD8+ T cells. We concluded that both antigen-specific IFN-γ producing CD4+ Th1 cells and IFN-γ producing CD8+ T cells contribute to the long term protection in individuals with a history of CL. This proves the importance of CD8+ T cells as a source of IFN-γ in Th1-like immune responses

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

An Analytical Research on Determination of Beam and Column Contribution to Plastic Energy Dissipation of RC Frames

Determination of capacities of structural members, both in terms of strength and deformation, and estimation of seismic demand are essential issues in earthquake-resistant design. In energy-based design and evaluation, both the structural capacity and the demand imposed by earthquake are considered in terms of energy and accordingly energy dissipation capacity of the structure is associated with seismic energy demand. Plastic energy dissipation of structures under monotonic lateral loading may be obtained by using the resultant pushover curves of nonlinear static analyses. However, the time variation of individual contribution of structural members to the dissipated plastic energy cannot be determined. In this study, the contribution of beam and column deformations to the plastic energy dissipated in multistory reinforced concrete (RC) frames is determined by using nonlinear time history (NLTH) analysis. It is found that rotational deformations of beams are dominant in plastic energy dissipation. Accordingly, some linear relations considering the contribution of dissipated plastic energy in beam plastic hinges to the total plastic energy dissipation of RC frames are derived. Pushover analysis of frames in conducted and the area under the resultant pushover curve is determined to satisfy the mean value of the maximum plastic energy dissipated in frames during the selected earthquakes. The interstory drift ratios are calculated and compared with the interstory drift ratios directly obtained from NLTH analyses. The results are evaluated and presented by graphs and tables