Synthesis, Cytotoxicity Assessment, and Molecular Docking of 4-Substituted-2-p-tolylthiazole Derivatives as Probable c-Src and erb Tyrosine Kinase Inhibitors

In the current project we focused on the synthesis of 4-Substituted-2-p-tolylthiazole derivatives. Cytotoxicity of synthesized compounds were evaluated against T47D breast cancer cell line and also all of the final compounds 3−7 were docked into the active site of c-Src and erb tyrosine kinases. Compound 4 was the most potent derivative in cytotoxicity assay (IC50 = 2.5 µg/mL) and it was also the most potent inhibitor of erb tyrosine kinase (Binding free energy: −10.18 kcal/mol).(doi: 10.5562/cca1939

Restorative Effect of Vitamin E Supplementation on Hepatic Lipid Peroxidation and Lipid Profile Changes Induced by Sublethal γ- Radiation in BALB/c Mice

ABSTRACT In order to find a prophylactic supplementation for individuals who are at risk of exposure to ionizing radiation, we attempted to evaluate the effect of Vitamin E (Vit-E), a biological free radical scavenger, on restoration of hepatic lipid peroxidation (LPO) and lipid profile (LP) changes induced by sublethal γ-radiation in BALB/c mice. The concentrations of cholesterol and phospholipid were determined in control and irradiated mice. Also, changes in lipid peroxidation and lipid profile were assessed by measuring the level of malonyldialdehyde, lipid hydroperoxides, and conjugated dienes. Our results showed that sublethal γ-radiation caused significant changes in hepatic lipid peroxidation and lipid profile. However, Vit-E supplementation was able to restore the changes of lipid peroxidation and lipid profile in irradiated mice. We have concluded that the mice that received Vit-E supplementation were able to tolerate biomembrane damage provoked by 1.09 Gy for 3 days γ-radiation. This supports the hypothesis that Vit-E may afford an efficient protection against ionizing radiation. However additional studies using higher doses of γ-irradiation should be performed

Synthesis and In Vitro Cytotoxic Activity of N-2-(2-Furyl)-2-(chlorobenzyloxyimino)Ethyl Ciprofloxacin Derivatives

Quinolone are a class of potent broad-spectrum antibacterial drugs that target the bacterial type II DNA topoisomerases (DNA gyrase) and topoisomerase IV. In the present study, the synthesis and evaluation of cytotoxicity activity of a new series of N-pipearzinyl quinolones containing N-2-(furyl-2-yl)-2-(chlorobenzyloxyimino) ethyl moiety (6a-c) have been studied. Preliminary screening showed that one of the new compounds, namely 7-(4-(2-(3-chlorobenzyloxyimino)-2-(furan-2-yl) ethyl) piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (6b) showed significant cytotoxic activity against human breast tumor cell lines

The association of dietary approach to stop hypertension (DASH) diet with hospitalization risk in patients with COVID-19

Summary: Background and aim: Given the importance of dietary habits in the immune system, the current study aimed at investigating the association between Dietary Approach to Stop Hypertension (DASH) diet and risk of hospitalization due to COVID-19. Methods: Dietary data of 141 patients with COVID-19 were collected using 147-item food frequency questionnaire. DASH score in this cross-sectional study was calculated based on eight components, including fruits, vegetables, legumes and nuts and seeds, whole grains, low-fat dairy, red or processed meats, sweetened beverages, and sodium. Multivariable logistic regression models were applied to estimate the OR and 95% CI for hospitalization due to COVID-19 in each tertile of DASH score. Results: Mean ± SD of DASH score in inpatients (n=74) and outpatients (n= 87) was 22.5 ± 4.57 and 25.34 ± 4.23, respectively. The risk of hospitalization in the highest tertile of DASH score was 81% lower than the lowest tertile (OR=0.19, 95%CI: 0.07–0.55, P trend = 0.001 after adjustment for age, sex, BMI, energy intake). Also, more intake of fruits, vegetables and low-fat dairy products and less intake of sodium, red and processed meat were each significantly associated with reduced risk of hospitalization due to COVID-19. Conclusions: Our data provide evidence that adherence to DASH-style diet was associated with lower risk of hospitalization due to COVID-19

Encapsulation of Curcumin in Diblock Copolymer Micelles for Cancer Therapy

Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P<0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P<0.05). Average tumor size and weight were significantly lower in PNPC group than control (P<0.05). PNPC increased proapoptotic Bax protein expression (P<0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P<0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P<0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response

Purification and biochemical characterization of two novel antigens from Leishmania major promastigotes

The identification and characterization of antigens that elicit human T cell responses is an important step toward understanding of Leishmania major infection and ultimately in the development of a vaccine. Micropreparative SDS-PAGE followed by electrotransfer to a PVDF membrane and elution of proteins from the PVDF, was used to separate 2 novel proteins from L. major promastigotes, which can induce antibodies of the IgG2a isotype in mice and also are recognized by antisera of recovered human cutaneous leishmaniasis subjects. Fractionation of the crude extract of L. major revealed that all detectable proteins of interest were present within the soluble Leishmania antigens (SLA). Quantitation of these proteins showed that their expression in promastigotes is relatively very low. Considering the molecular weight, immunoreactivity, chromatographic and electrophoretic behavior in reducing and non-reducing conditions, these proteins are probably 2 isoforms of a single protein. A digest of these proteins was resolved on Tricine-SDS-PAGE and immunoreactive fragments were identified by human sera. Two immunoreactive fragments (36.4 and 34.8 kDa) were only generated by endoproteinase Glu-C treatment. These immunoreactive fragments or their parent molecules may be ideal candidates for incorporation in a cocktail vaccine against cutaneous leishmaniasis

Plant-based diet and COVID-19 severity: results from a cross-sectional study

Although previous findings have shown the beneficial role of healthy eating pattern on the human immune system, the association between plant-based diet and COVID-19 severity has not yet been elucidated. This study aimed to determine the possible role of plant-based diet index (PDI) in COVID-19 severity. This cross-sectional, multicentral study was conducted on 141 patients with confirmed COVID-19. Dietary intakes of the patients were evaluated using a validated food frequency questionnaire. Then, PDI was compared between patients who needed to be hospitalised (considered severe cases), and those who got treatment at home (considered non-severe cases). After adjustment for confounders including age, sex, energy intake and body mass index, lower odds of hospitalisation were found for participants having a greater score of overall PDI (OR per 10 units increase: 0.42; 95% CI 0.22 to 0.80) and healthy PDI (OR per 10 unit increase: 0.45; 95% CI 0.26 to 0.78). In conclusion, our data presented that there is a relation between PDI and lower risk of hospitalisation in COVID-19 patients, possibly through boosting the immune function

Identification of novel Leishmania major antigens that elicit IgG2a response in resistant and susceptible mice

Experimental murine models with high, intermediate and low levels of genetically based susceptibility to Leishmania major infection reproduce almost entire spectrum of clinical manifestations of the human disease. There are increasing non-comparative studies on immune responses against isolated antigens of L. major in different murine strains. The aim of the present study was to find out whether there is an antigen that can induce protective immune response in resistant and susceptible murine strains. To do that, crude antigenic extract of procyclic and metacyclic promastigotes of L. major was prepared and subjected to SDS-PAGE electrophoresis. Western-blotting was used to search for antigen(s) capable of raising high antibody level of IgG2a versus IgG1 in the sera of both infected resistant and susceptible strains. Two novel antigens from metacyclic promastigotes of L. major (140 and 152 kDa) were potentially able to induce specific dominant IgG2a responses in BALB/c and C57BL/6 mice. The 2 antigens also reacted with IgG antibody of cutaneous leishmaniasis patients. We confirm that 140 and 152 kDa proteins of L. major promastigotes are inducing IgG production in mice and humans