The spectrum of clinical efficacy of Methotrexate (MTX) is broad in that MTX is used in the treatment of certain cancers, severe psoriasis and rheumatoid arthritis.Various mechanisms by which cancer cells grown in tissue culture become resistant to anticancer drugs. The use of multiple drugs with different mechanisms of entry into cells and different cellular targets allows for effective chemotherapy and high cure rates. In an efforts to develop effective strategies that increase the therapeutic potential of anticancer drugs with less systemic toxicity ,are being directed towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination with anticancer drugs. A promising approach to improve the cancer cell selectivity of methotrexate is the chemical transformation into reversible derivatives which convert the conjugate to the parent drug by virtue of enzyme within cancer tissue. The present study includes the synthesis of two derivatives of methotrexate which are :-Schiff base methotrexate-silibinin conjugate ( compound 5), and Methotrexate-silibinin conjugate (compound 6).The synthesis of the target compounds was accomplished following multistep reaction procedures. The chemical reactions were followed up and purity of the products was checked by TLC. The structures of the final compounds and their intermediates were characterized and identified by their melting points, infrared spectroscopy, 1H-NMR and elemental microanalysis(C H N S).The anticancer activity of these compounds was investigated by HEP-2 cell line(Larynx carcinoma), which showed that compounds 5 and 6 have the higher activity than methotrexate or silibinin alone.These are promising data for the discovery of new anticancer agents in future. These compounds may deliver the parent drug selectively into the cancer cells to be hydrolyzed by enzymes that are elevated in tumor tissues compared with normal tissues . Keywords: Methotrexate, Silibinin, Cancer treatment resistance, Folate receptor, Cancer cell targeting.
Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by
Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq)
... Show MoreVariation in the numbers of pectoral fin spines and rays, pelvic fin rays, gill rakers on the first gill arch, anal fin rays, and the number of vertebrae of Silurus triostegus Heckel were examined in specimens from 16 localities that span its entire distribution range in the Tigris, Euphrates, and Shatt al-Arab rivers in Iraq. The mean number of the six meristic traits increases toward high latitudes with maximum and minimum values in the north and south of Iraq. Based on cluster analysis and PCA, the Mesopotamian river samples were clearly separated into three distinct groups. The upper Tigris populations were isolated from those of the middle and southern populations of this river and from those of
The research work was conducted to investigate the effect of oral administration of aqueous extract of turmeric at doses of (5, 10) mg/kg body weight for two weeks daily by determining the genotoxic effect (mitotic index), evaluation of immunological effect (IgG, IgM, IgA, C3, C4) and measuring fertility hormones (follicles stimulation hormone/FSH, lutenising hormone/LH) levels with histological examinations of female albino swiss mice ovaries in comparison with control (normal saline). A clear effect in increasing mitotic activity was reveled for both doses in comparison with control. Results also showed a significant increase in the value of all immunological parameters at both doses, in comparison with control. Also, obvious rais
... Show MoreRadon is the most dangerous natural radioactive component affecting the human population, since it is a radioactive gas that results from the decomposition process of uranium deposits in soil, rocks, and water, and it is damaging both humans and the ecosystem. The radon concentrations and exhalation rate in soil samples from various locations were determined using a passive approach with a CR-39 (CR-39 is Columbia Resin #39; it is allyl diglycol carbonate C12H18O7) detector in Amiriya region in Baghdad Governorate. The average values of radon concentrations are ranged from 47.3 to 54.2 Bq·m−3. From the obtained results, we can conclude that the values of all studied locations are
Background: Periodontitis and Atherosclerosis Cardiovascular disease are chronic inflammatory diseases which are highly prevalent. During the last two decades, there has been an increasing interest in the impact of oral health on atherosclerosis and subsequent cardiovascular disease.Aims of the study wereto evaluate the periodontal health status in study groups (Atherosclerotic cardiovascular disease patients with chronic periodontitis and patients having chronic periodontitis),to estimate the serum levels of Matrixmetalloproteinase-8(MMP-8) and high sensitive C-reactive protein(hs CRP) in study and control groups and compare between them. Also,test the correlation between the serum levels of MMP-8 and hs CRP with clinical periodontal par
... Show MoreAbstract: This study was aimed to investigate the effect of two doses of pregabalin (PGB) on hormonal level and sexual activity in female albino rats. Ninety female rats with age (9-10 weeks) and weight (200±20 g) were divided into three major groups of thirty rats. First group was considered as control G1, the second G2 and third G3 groups were exposed to PGB into two doses 150, and 300 mg/kg body weight per day respectively. Each major group was divided into three subgroups (subgroup A, B, and C of each has ten rats), the treatments last for one month for subgroup A, two months for subgroup B, and three months for subgroup C. Five rats from each subgroup were placed separately into two breeding cages with two isolated males and wait
... Show MoreThis study aims to track and analysis Hitler's personality by explaining the impact of the social environment in shaping his behavior and addressing the defeat of Germany in the World War 1 and its impact on building his political personality and included his political activism and his policy to get rid of the terms of the Versailles Military Treaty in the light of his plans in his book ( Kifahi) The nature of the study had to be divided into an introduction and two topics followed by the conclusion of the most important results, in addition to a list of references and a summary in English and from God the Good luck.