Infliximab substantially re-silenced Wnt/β-catenin signaling and ameliorated doxorubicin-induced cardiomyopathy in rats

The release of inflammatory cytokines, namely tumor necrosis factor-α (TNF-α), plays an important role in the pathogenesis of cardiomyopathy. TNF-α increases in plasma and in myocardium of heart failure patients. We aimed to investigate the role of TNF-α inhibitor (infliximab; IFX) in regulating dilated cardiomyopathy (DCM) induced in rats. DCM was induced in rats by doxorubicin (DOX; 3.5 mg. kg⁻¹, i.p) twice weekly for 3 weeks (21 mg. kg⁻¹ cumulative dose). DCM rats were treated with RPL (1 mg. kg⁻¹ orally, daily), IFX (5 mg. kg⁻¹; i.p. once) or their combination for 4 weeks starting next day of last DOX dose. Echocardiography was conducted followed by a collection of blood and left ventricle (LV) for biochemical and histological investigations. DCM rats revealed deteriorated cardiac function (increased CK-MB activity, LVIDs, LVIDd, ESV, and EDV, while decreased EF% and FS%), hypertrophy (increased HW/TL, β-MHC, and α-actin), inflammation (increased IL-1β, IL-6, and TNF-α). The activation of Wnt/β-catenin along with increased gene expression of RAS components (RENIN, ACE, and AT1) were evident. LV architecture also revealed abnormalities and some degree of fibrosis. Treatment with RPL and/or IFX suppressed TNF-α and consequently improved most of these parameters suppressing Wnt/β-catenin/RAS axis. Combined RPL and IFX treatment was the best among all treatments. In conclusion, Wnt/β-catenin/RAS axis is implicated in DOX-induced cardiomyopathy. The upstream TNF-α was proved for the first time in-vivo to stimulate this axis where its inhibition by RPL or IFX prevented DCM. Targeting this axis at two points using RPL and IFX showed better therapeutic efficacy.     

Design,Synthesis, Anticancer Evaluation and Molecular Modeling Studies of New Thiazolidinone-Benzoate Scaffold as EGFR Inhibitors,Cell Cycle Interruption and Apoptosis Inducers in HepG2

Synthesis of new anticancer candidates with protein kinases inhibitory potency is a major goal of pharmaceutical science and synthetic research. This current work represents the synthesis of a series of substituted benzoate-thiazolidinones. Most prepared thiazolidinones were evaluated in vitro for their potential anticancer activity against three cell lines by MTT assay, and they found to be more effective against cancer cell lines with no harm toward normal cells. Thiazolidinones 5 c and 5 h were further evaluated to be kinase inhibitors against EGFR showing effective inhibitory impact (with IC₅₀ value; 0.2±0.009 and 0.098±0.004 μM, for 5 c and 5 h , respectively). Furthermore, 5 c and 5 h have effects on cell cycle and apoptosis induction capability in HepG2 cell lines by DNA-flow cytometry analysis and annexin V-FITC apoptosis assay, respectively. The results showed that they have effect of disrupting the cell cycle and causing cell mortality by apoptosis in the treated cells. Moreover, molecular docking studies showed better binding patterns for 5 c and 5 h with the active site of the epidermal growth factor receptor (EGFR) protein kinase (PDB code 1M17). Finally, toxicity risk and physicochemical characterization by Osiris method was performed on most of the compounds, revealing excellent properties as possible drugs.     

Biogeographical relations of a hyperarid desert flora in eastern Egypt

The floristic composition and geographical elements of the study area were analysed resulted in 328 species representing 206 genera in 55 families. This study confirmed the record of fourteen species, mostly weeds, which can be considered as new additions to the flora of the study area. Therophytes were the dominant life form, while mono‐ and bi‐regional Saharo‐Sindian geoelements were the most represented. Ten species showed dominancy with their Q‐values ranged between 0.802 and 0.2, where Zilla spinosa and Zygophyllum coccineum were of common occurrence. Application of cluster analysis and DCA ordination techniques produced four major floristic groups (A–D) comprising seven subgroups. The correlation coefficients (r) between the different subgroups revealed high significant correlations (P = 0.01) between floristic group (B) and subgroup (C₂) and between subgroups (D₁) and (D₂). Significant correlations (P = 0.05) occurred between subgroup (D₁) and both of (A₁) and (C₂). Comparing the floristic similarities between this investigation and other relevant studies were presented and discussed. On the other hand, the low similarity index between the study area and Sinai may be attributed to the geographical position of both deserts where Sinai desert is part of the Irano‐Turanian region, while the Eastern Desert is a part of the Saharo‐Sindian region.     

Tables for Testing the Equality of Two Proportions when Prior Information on their Common Value May be Available

In testing the equality of two proportions, one may define a rejection point T? such that if the test statistic T (in this paper, the ordinary Pearsonian chi-squared) exceeds T? then the hypothesis may safely be rejected, whatever the common value p of the two proportions may be; and similarly define an acceptance point A? such that if T ≦ T? then one may safely accept. These points may be refined if prior information is available, for example that p must lie in the central interval (c, 1 – c) or one of the extremal intervals (v, w) and (1 – w, 1 – v). Smallsample tables are provided both for the unrestricted case and for situations where one has such prior information.     

Thermoluminescence characteristics of lithium borosilicate glass doped with Sm2O3

Lithium borosilicate glass composite (SiO₂–Li₂CO₃–H₃BO₃) doped with various concentrations of Sm₂O₃ (0–0.7 mole %) was prepared using the melt quenching method. The investigated thermoluminescence (TL) characteristics of the prepared system revealed that the highest TL response was obtained for this glass composite at 0.05 mol% Sm₂O₃. In this study, the 0.05 mol% Sm₂O₃‐doped lithium borosilicate glass composite was subjected to detailed dosimetric investigation in terms of its annealing condition, dose–response, and minimum detectable dose. The reproducibility of the response, thermal characteristics, and optical fading were also studied. The obtained results showed that the prepared glass composite had a linear dose–response over the wide gamma dose range 2Gy to 2 kGy, as well as reasonable thermal fading and excellent reproducibility. These attributes render the composite under investigation promising for utilization in radiation detection.     

Joint action of nuclear polyhedrosis virus and chemical insecticides against the black cutworm, Agrotis ipsilon (Hufn.)

A polyhedrosis virus disease was isolated from the larvae of Agrotis ipsilon. Isolation of causative agent from the infected larvae again showed to be positive. Microscopic examination of the infected larvae (by means of a light microscope) gave an evidence of the development of the polyhedral inclusion bodies (PIB) in all typical tissues where the virus is known to develop. Examination by an electron microscope showed various irregular shaped polyhedra; their diameter being about 1.5 to 3.5 mu. Most of these polyhedra were hexagonal and they measured about 2.2 mu. Experimental studies were conducted to investigate its pathogenicity alone and when combined with chemical insecticides. The joint action of the nuclear polyhedrosis virus of A. ipsilon (AINPV) combined with four chemical insecticides namely Fenvalerate, Decamethrin, Cypermethrin and Methomyl was assessed against the second instar larvae of A. ipsilon. Results showed that Decamethrin was the most toxic compound followed by Cypermethrin and Fenvalerate while Methomyl was the least toxic, the median lethal concentrations (LC50) were 0.25, 0.77, 14 and 450 ppm, respectively. The LC50 value of AINPV was 12 x 10(6) PIB/ml. Mixtures containing sublethal concentrations (LC25 and less) of both AINPV and any of the tested insecticides showed synergistic effects. On the other hand, an additive effect was observed with combinations containing doses of chemical insecticides over the range between LC25 and LC50 values.