PHYTOCHEMICAL ANALYSIS, ASSESSMENT OF ANTIPROLIFERATIVE AND FREE RADICAL SCAVENGING ACTIVITY OF MORUS ALBA AND MORUS RUBRA FRUITS

Objective: Mulberry is a nontoxic commonly eaten plant, belongs to the Morus and used in folk medicine in the remedy of dysentery, antiphlogistic, diuretic, expectorant, and antidiabetic. The purpose of this study is to evaluate the antiproliferative and radical scavenging activity of the total alcoholic and successive fractions thereof of Morus alba and Morus rubra fruits. In addition, the chemical composition of the bioactive fractions of each species was investigated.Methods: The antiproliferative potential of 8 extracts on 4 human cancer cell lines, hepatocellular carcinoma (HepG2), Caucasian breast adenocarcinoma (MCF7), prostate (PC3), and colon carcinoma (HCT116) in addition to one normal cell line namely human normal immortalized skin fibroblast cells (BJ1) were carried out. Cell viability was determined using MTT assay. The potency was compared with the reference drug doxorubicin. These extracts were also assayed for 1,1-diphenyl-2-hydrazyl free radical scavenging activities. After saponification of the n-hexane fraction, unsaponifiable matter and fatty acid methyl esters were analyzed by gas liquid chromatography (GLC). The chemical composition of the bioactive fractions was investigated using gas chromatography/mass spectrometry (GC/MS) analysis.Results: All the extracts showed significant free radical scavenging activity dose-dependently. The n-hexane and dichloromethane (DCM) fractions of M. rubra exhibited potent cytotoxic activity on almost cancer cell lines. In the same pattern, ethyl acetate (EtOAc) of M. rubra has moderate cytotoxic activity against all cell lines except HepG2. DCM fraction of M. alba possessed both radical scavenging and high potential antiproliferated activities against HCT116 and MCF7 with inhibitory concentration of 43.9 and 32.3 μg/ml, respectively, while it showed no cytotoxic effect on BJ1. GLC analysis showed the major hydrocarbons in M. alba and M. rubra were heptacosane and docosane, respectively. Sterols were similar in both species but with different ratios and cholesterol was the major one. Palmitic and margaric were the major saturated fatty acid while arachidonic was the major unsaturated fatty acid in both species. GC/MS analysis showed the main compound in DCM fraction of each Morus species was palmitic acid. Furthermore, 1,11-bis-(methoxycarbonyl-ethenyl)-10,2-dihydroxy-cycloeicosane and linolelaidic acid, methyl ester were the main compounds in the EtOAc fraction of each Morus species. Whereas, the main compounds in alcoholic extract of M. alba and M. rubra were methyl-14-methyl-pentadecanoate and 1,2-O-isopropylyidene-4-nonene-1,2,3-triol, respectively.Conclusions: The results observed remarkable biological activity of the successive fractions of M. rubra more than those of M. alba and confirmed its importance as a natural bioactive source. Morus species are good candidates to be promising as possible sources for future antitumor and antioxidants in food and pharmaceutical formulations. The strong activity partly explains the potential effects of Morus species for the treatment of cancer and degenerative diseases caused by free radicals

Expression Of Glucocorticoid Receptor Beta (GCR Β) In Asthmatic Patients And Its Correlation With Clinical Severity And Pulmonary Functions

N e w Y o r k S c i e n c e J o u r n a l 2 0 1 0 ; 3 Expression Of Glucocorticoid Receptor Beta (GCR Β) In Asthmatic Patients And Its Correlation With Clinical Severity And Pulmonary Functions Engy Yousry Elsayed , Enas M Foda, khaled AH Mohammed, Hassan Shalaby, Amal Z. Abd El-Halem* and Eman Ramzy** Internal Medicine, Clinical Pathology* and Chest** Departments Faculty Of Medicine, Ain Shams University, cairo, Egypt. [email protected] ABSTRACT Background: Glucocorticoids are the gold standard treatment of bronchial asthma. Although the majority of patients with asthma respond favorably to inhaled and systemic steroid therapy, a subset of asthmatics failed to demonstrate a satisfactory response even to systemic glucocorticoid therapy. GCR β (glucocorticoid receptor beta) is a hormone binding deficit isoform of GCR (glucocorticoid receptor) which has been isolated in humans and when over expressed, it may function as a dominant negative modulator of GCR. Aim of the work: This study was designed to determine the percentage of expression of GCRβ on PBMCs: (peripheral blood mononuclear cells )of asthmatic patients and to correlate it with the clinical severity and pulmonary functions. Subjects and Methods: 60 asthmatic patients (41 males, 19 females) and 20 healthy controls were enrolled in this study. Asthmatics were classified according to GINA guidelines (2002) into mild, moderate and severe asthma. They were subdivided into asthmatic on inhaled corticosteroid (ICS) (n=35) and those not on ICS (n=25). For all studied groups, spirometeric pulmonary functions and immunohisto-chemistry staining of PBMC S were performed to analyze percentage of expression of GCRβ on PBMCs. Results: It showed that the percentage of expression of GCRβ on PBMC S were statistically higher in all asthmatic patient groups compared to control, with higher % of expression in those not on ICS. Also a statistical significant higher % of expression of GCR β in severe asthmatics compared to both mild and moderate groups was detected. In conclusion: This study highlights the importance of glucocorticoid receptor beta isoform in pathogenesis of bronchial asthma and this may be directly linked to asthma severity and can affect the response to medications especially ICS

Asc-Dependent and Independent Mechanisms Contribute to Restriction of Legionella Pneumophila Infection in Murine Macrophages

The apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) is an adaptor molecule that mediates inflammatory and apoptotic signals. Legionella pneumophila is an intracellular bacterium and the causative agent of Legionnaire's pneumonia. L. pneumophila is able to cause pneumonia in immuno-compromised humans but not in most inbred mice. Murine macrophages that lack the ability to activate caspase-1, such as caspase-1−/− and Nlrc4−/− allow L. pneumophila infection. This permissiveness is attributed mainly to the lack of active caspase-1 and the absence of its down stream substrates such as caspase-7. However, the role of Asc in control of L. pneumophila infection in mice is unclear. Here we show that caspase-1 is moderately activated in Asc−/− macrophages and that this limited activation is required and sufficient to restrict L. pneumophila growth. Moreover, Asc-independent activation of caspase-1 requires bacterial flagellin and is mainly detected in cellular extracts but not in culture supernatants. We also demonstrate that the depletion of Asc from permissive macrophages enhances bacterial growth by promoting L. pneumophila-mediated activation of the NF-κB pathway and decreasing caspase-3 activation. Taken together, our data demonstrate that L. pneumophila infection in murine macrophages is controlled by several mechanisms: Asc-independent activation of caspase-1 and Asc-dependent regulation of NF-κB and caspase-3 activation

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

GIZA 11 AND GIZA 12; TWO NEW FLAX DUAL PURPOSE TYPE VARIETIES

Sixteen flax genotypes {13 promising lines and 3 check varieties viz., Giza 8 (oil type), Sakha 1 (dual purpose type) and Sakha 3 (fiber type)} were evaluated for straw, seed, oil yields and their related traits under twelve different environments; four locations (Sakha, Etay El-Baroud, Ismailia and Giza Exp. Stations through three successive seasons (2011/12, 2012/13 and 2013/14). These materials were evaluated in a randomized complete blocks design with three replications at the twelve above-mentioned environments. The analysis of variance revealed highly significant differences among genotypes (G), environments (E) and G x E interaction for all studied traits except straw weight per plant, indicating a wide range of variation among genotypes, environments and these genotypes exhibited differential response to environmental conditions. The significant variance due to residual for all characters except both straw weight per plant and oil yield per fad indicated that genotypes differed with respect to their stability suggesting that prediction would be difficult, which means that mean performance alone would not be appropriate. Interaction component of variance (σ2ge) was less than the genotypic variance (σ2g) for all characters, indicating that genotypes differ in their genetic potential for these traits. This was reflected in high heritability and low discrepancy between phenotypic (PCV) and genotypic (GCV) coefficients of variability values for these traits indicating the possibility of using each of long fiber percentage, plant height and technical stem length as selection indices for improving straw weight per plant, as well as, using 1000-seed weight and capsules number per plant as selection indices for improving seed weight per plant. Yield stability (YSi) statistic indicated that S.541-C/3 and S.541-D/10 gave high mean performance and stability for straw, fiber, seed and oil yields per fad in addition to oil percentage, capsules number per plant and 1000-seed weight. Therefore, the two genotypes well be released under the name Giza 11 and Giza 12, respectively. These newly released varieties are of dual purpose type for straw, fiber, seed and oil yield. They may replace the low yielding cultivars Giza 8, Sakha 1 and Sakha 3

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Search for a heavy Higgs boson decaying into two lighter Higgs bosons in the tau tau bb final state at 13 TeV

A search for a heavy Higgs boson H decaying into the observed Higgs boson h with a mass of 125 GeV and another Higgs boson h(S) is presented. The h and h(S) bosons are required to decay into a pair of tau leptons and a pair of b quarks, respectively. The search uses a sample of proton-proton collisions collected with the CMS detector at a center-of-mass energy of 13TeV, corresponding to an integrated luminosity of 137 fb(-1). Mass ranges of 240-3000 GeV for m(H) and 60-2800 GeV for m(hS) are explored in the search. No signal has been observed. Model independent 95% confidence level upper limits on the product of the production cross section and the branching fractions of the signal process are set with a sensitivity ranging from 125 fb (for m(H) = 240 GeV) to 2.7 fb (for m(H) = 1000 GeV). These limits are compared to maximally allowed products of the production cross section and the branching fractions of the signal process in the next-to-minimal supersymmetric extension of the standard model.Peer reviewe

Measurements of the Electroweak Diboson Production Cross Sections in Proton-Proton Collisions at root s=5.02 TeV Using Leptonic Decays

The first measurements of diboson production cross sections in proton-proton interactions at a center-of-mass energy of 5.02 TeV are reported. They are based on data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 302 pb(-1). Events with two, three, or four charged light leptons (electrons or muons) in the final state are analyzed. The WW, WZ, and ZZ total cross sections are measured as sigma(WW) = 37:0(-5.2)(+5.5) (stat)(-2.6)(+2.7) (syst) pb, sigma(WZ) = 6.4(-2.1)(+2.5) (stat)(-0.3)(+0.5)(syst) pb, and sigma(ZZ) = 5.3(-2.1)(+2.5)(stat)(-0.4)(+0.5) (syst) pb. All measurements are in good agreement with theoretical calculations at combined next-to-next-to-leading order quantum chromodynamics and next-to-leading order electroweak accuracy

Measurement of the top quark mass using events with a single reconstructed top quark in pp collisions at root s=13 TeV

Abstract:A measurement of the top quark mass is performed using a data sample en-riched with single top quark events produced in thetchannel. The study is based on proton-proton collision data, corresponding to an integrated luminosity of 35.9 fb−1, recorded at√s= 13TeV by the CMS experiment at the LHC in 2016. Candidate events are selectedby requiring an isolated high-momentum lepton (muon or electron) and exactly two jets,of which one is identified as originating from a bottom quark. Multivariate discriminantsare designed to separate the signal from the background. Optimized thresholds are placedon the discriminant outputs to obtain an event sample with high signal purity. The topquark mass is found to be172.13+0.76−0.77GeV, where the uncertainty includes both the sta-tistical and systematic components, reaching sub-GeV precision for the first time in thisevent topology. The masses of the top quark and antiquark are also determined separatelyusing the lepton charge in the final state, from which the mass ratio and difference aredetermined to be0.9952+0.0079−0.0104and0.83+1.79−1.35GeV, respectively. The results are consistentwithCPTinvariance

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century