Chemical screening identifies the β-Carboline alkaloid harmine to be synergistically lethal with doxorubicin.

Despite being an invaluable chemotherapeutic agent for several types of cancer, the clinical utility of doxorubicin is hampered by its age-related and dose-dependent cardiotoxicity. Co-administration of dexrazoxane as a cardioprotective agent has been proposed, however recent studies suggest that it attenuates doxorubicin-induced antitumor activity. Since compounds of natural origin present a rich territory for drug discovery, we set out to identify putative natural compounds with the view to mitigate or minimize doxorubicin cardiotoxicity. We identify the DYRK1A kinase inhibitor harmine, which phosphorylates Tau that is deregulated in Alzheimer's disease, as a potentiator of cell death induced by non-toxic doses of doxorubicin. These observations suggest that harmine or other compounds that target the DYRK1A kinase my offer a new therapeutic opportunity to suppress doxorubicin age-related and dose-dependent cardiotoxicity

EVALUATION OF GROUNDWATER QUALITY OF SIWA OASIS

In discussing the water quality evaluation for use in different purposes, the author will briefly examine some of the major important water quality standards. These standards serve as a basis for appraisal of the results of chemical water analysis in terms of suitability of the water for various intended uses. According to total dissolved salts (TDS),  major  ions as cations ( Ca2+, Mg2+, Na+, K+), anions (CO₃2â», HCO₃â»Â  ,SOâ‚„2â», Clâ»), with some heavy metals such as Al3+, B3+ , Cd2+, Co2+, Cr3+, Cu2+, Fe3+, Mn2+,  Mo2+, Ni2+,  Pb2+, Sr2+, V2+   and Zn2+  The results  indicate  that  the samples of Nubian sandstone aquifer is suitable for drinking of human and livestock , suitable for laundry purposes and for irrigation. While the samples of Fractured dolomite limestone aquifer are unsuitable for drinking and irrigation.Â

КЛАССИФИКАЦИЯ ОБРАЗОВ ПРЕЗИДЕНТА РОССИИ В.В. ПУТИНА В КАЧЕСТВЕННОЙ ИОРДАНСКОЙ ПРЕССЕ

The authors of this article have studied the texts of the Jordanian popular and quality papers - the government newspaper Al-Raya and the independent newspaper Al-Ghad. We have analyzed about 50 materials that directly or indirectly mention Vladimir Putin for the period from March 2011 (when the civil war in Syria has started) till February 2018. We have focused on the images of Vladimir Putin that were created in the Jordanian media. Conventionally, they fall under one of the three categories: “Putinfriend”, “Putin-enemy” or “Putin-president of Russia”.Авторами изучены тексты иорданских популярных изданий «Аль-Раи» и «Аль-Гхад» за период с марта 2011 по февраль 2018 гг., в которых прямо или косвенно упоминается президент России Владимир Путин. Авторы выделяют классификацию образов президента РФ: «Путиндруг», «Путин-враг» и «Путин-Президент России». Изучая медиатексты, авторы пришли к выводу, что ни правительственные, ни независимые иорданские издания не интересуют такие популярные для западных СМИ темы, как российская оппозиция, Алексей Навальный, ЛГБТ, права человека и демократия. Образ российского лидера в иорданской прессе создается через его внешнеполитические действия

Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation.

Histamine 4 receptor (H4R) is a novel target for the pharmacological modulation of histamine-mediated immune signals during inflammatory diseases. The purpose of this study was to assess the effects of the H4R agonist 4-methylhistamine dihydrochloride (4-MeH) and antagonist JNJ7777120 (JNJ) in the inflamed rat knee. Animals were fasted for 18h before a single dose of 4-MeH or JNJ (30mg/kg) was administered intraperitoneally (i.p.), both followed by intra-articular (i.a.) injection of LPS 2h later. Blood and synovial fluid were collected after a short incubation period and TNF-α, NF-κB, and IkB-α levels were measured via flow cytometry. Additionally, we assessed the effects of H4R engagement on the expression of IL-1β, TNF-α, and NF-κB mRNAs and the protein levels of TNF-α, NF-κB, JAK-1, and STAT-3 in the inflamed knee tissue. These results revealed increased TNF-α and NF-κB expression and decreased IkB-α levels in both the LPS alone and 4-MeH treated groups in whole blood and synovial fluid. Further, IL-1β, TNF-α, and NF-κB mRNA levels were significantly increased and western blot analysis confirmed increased expression of TNF-α, NF-κB, JAK-1, and STAT-3 in both LPS and 4-MeH treatment groups. Furthermore, these increases were completely inhibited in the inflamed knee tissue of the JNJ-treated group. Thus, the inhibition of inflammatory mediators and signaling pathways by the H4R antagonist JNJ suggests the anti-arthritic importance of this molecule

Stimulation of the histamine 4 receptor with 4-methylhistamine modulates the effects of chronic stress on the Th1/Th2 cytokine balance.

Alterations to the immune system caused by stress have been considered to markedly increase the risk for immune-related diseases such as cancer and autoimmune disorders. We investigated the potential anti-stress effects of the histamine 4 receptor (H4R) agonist, 4-methylhistamine (4-MeH), in a murine stress model. Mice were placed in 50ml conical centrifuge tubes for 12h followed by a 12h rest. The effects of treatment with 4-MeH (30mg/kg, i.p., twice daily) for 2 days were assessed. At 2 days after physical restraint, mice were sacrificed and tissues harvested. We evaluated the effects of 4-MeH treatment on CD4(+) T cell production, and intracellular IFN-γ and IL-4 expression in these cells. We also assessed IL-1β, IFN-γ, TNF-α, and IL-4 mRNA expression as well as IFN-γ, TNF-α, GITR, Ox40 and IL-4 protein expression in the spleen. The results showed that 4-MeH treatment of stressed mice results in a substantial increase in the CD4(+) T cells as well as in IFN-γ production by these cells. Compared to both untreated and stressed controls. In contrast, IL-4 expression decreased significantly following 4-MeH treatment of mice. Moreover, stimulation of the H4R resulted in up-regulated expression of IL-1β, IFN-γ and TNF-α mRNAs and decreased the expression of IL-4. Western blot analysis confirmed decreased protein expression of IFN-γ, TNF-α, GITR, Ox40 and increased IL-4 in the SC group and treatment of mice with 4-MeH reversed these effects. Our results confirm the significant impact of chronic stress on T cell function and production of Th1/Th2 mediators H4R

Angular momenta creation in relativistic electron-positron plasma

Creation of angular momentum in a relativistic electron-positron plasma is explored. It is shown that a chain of angular momentum carrying vortices is a robust asymptotic state sustained by the generalized nonlinear Schrodinger equation characteristic to the system. The results may suggest a possible electromagnetic origin of angular momenta when it is applied to the MeV epoch of the early Universe.Comment: 20 pages, 6 figure

The Scientific Foundations of Forecasting Magnetospheric Space Weather

The magnetosphere is the lens through which solar space weather phenomena are focused and directed towards the Earth. In particular, the non-linear interaction of the solar wind with the Earth's magnetic field leads to the formation of highly inhomogenous electrical currents in the ionosphere which can ultimately result in damage to and problems with the operation of power distribution networks. Since electric power is the fundamental cornerstone of modern life, the interruption of power is the primary pathway by which space weather has impact on human activity and technology. Consequently, in the context of space weather, it is the ability to predict geomagnetic activity that is of key importance. This is usually stated in terms of geomagnetic storms, but we argue that in fact it is the substorm phenomenon which contains the crucial physics, and therefore prediction of substorm occurrence, severity and duration, either within the context of a longer-lasting geomagnetic storm, but potentially also as an isolated event, is of critical importance. Here we review the physics of the magnetosphere in the frame of space weather forecasting, focusing on recent results, current understanding, and an assessment of probable future developments.Peer reviewe

Albumin administration in patients with decompensated liver cirrhosis: A meta-analytic update

End-stage liver disease and its related complications exert a huge disease burden and reduce the survival rates of many patients. Albumin administration for patients with decompensated liver cirrhosis has been a controversial topic of discussion. The aim of this study is to investigate whether albumin reduces the mortality and complications of liver cirrhosis compared to standard medical therapy (SMT) alone. Clinical trials in which albumin administration was compared to SMT in patients with liver cirrhosis were included in this meta-analysis. The primary outcome of this study was to evaluate the effect on reducing all-cause mortality. Ascites control, renal failure and hepatic encephalopathy were evaluated as secondary outcomes. Nine clinical trials with 1231 patients were recruited and analyzed using the quality effect model. Mortality rate was significantly reduced in the albumin group [relative risk (RR) 0.73, 95% confidence interval (CI) 0.56-0.96]. Heterogeneity was mild across all studies (I223.3%). Studies reporting long-term albumin (LTA) administration were found to have a significant decrease in mortality (RR 0.57, 95% CI 0.44-0.73). However, studies reporting short-term albumin administration were found to have no effect on mortality (RR 0.90, 95% CI 0.56-1.45). Furthermore, there was a significant decrease in the incidence of all secondary outcomes. This meta-analysis provides evidence that LTA administration is significantly effective in reducing the mortality of liver cirrhosis compared to SMT. Albumin administration was also shown to reduce the occurrence of ascites, renal failure and hepatic encephalopathy as complications of liver cirrhosis.Scopu

КЛАССИФИКАЦИЯ ОБРАЗОВ ПРЕЗИДЕНТА РОССИИ В.В. ПУТИНА В КАЧЕСТВЕННОЙ ИОРДАНСКОЙ ПРЕССЕ

The authors of this article have studied the texts of the Jordanian popular and quality papers - the government newspaper Al-Raya and the independent newspaper Al-Ghad. We have analyzed about 50 materials that directly or indirectly mention Vladimir Putin for the period from March 2011 (when the civil war in Syria has started) till February 2018. We have focused on the images of Vladimir Putin that were created in the Jordanian media. Conventionally, they fall under one of the three categories: “Putinfriend”, “Putin-enemy” or “Putin-president of Russia”.Авторами изучены тексты иорданских популярных изданий «Аль-Раи» и «Аль-Гхад» за период с марта 2011 по февраль 2018 гг., в которых прямо или косвенно упоминается президент России Владимир Путин. Авторы выделяют классификацию образов президента РФ: «Путиндруг», «Путин-враг» и «Путин-Президент России». Изучая медиатексты, авторы пришли к выводу, что ни правительственные, ни независимые иорданские издания не интересуют такие популярные для западных СМИ темы, как российская оппозиция, Алексей Навальный, ЛГБТ, права человека и демократия. Образ российского лидера в иорданской прессе создается через его внешнеполитические действия