Curcumin ameliorated myocardial infarction by inhibition of cardiotoxicity in the rat model

Cardiovascular diseases are the main cause of death globally. Many attempts have been done to ameliorate the pathological changes after the occurrence of myocardial infarction. Curcumin is touted as a polyphenol phytocompound with appropriate cardioprotective properties. In this study, the therapeutic effect of curcumin was investigated on acute myocardial infarction in the model of rats. Rats were classified into four groups; control, isoproterenol hydrochloride (ISO) (100 mg/kbw), curcumin (50 mg/kbw), and curcumin plus ISO treatment groups. After 9-day administration of curcumin, levels of lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents were measured to investigate the oxidative status in infarct rats received curcumin. By using H & E staining, tissue inflammation was performed. Masson’s trichrome staining was conducted to show cardiac remodeling and collagen deposition. The number of apoptotic cells was determined by using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Data showed the serum decrease of LDH, CK, and cTnI in infarct rats after curcumin intake compared to the rats given (ISO) ( P < 0.05). Curcumin was found to reduce oxidative status by reducing SOD and MDA contents ( P < 0.05). Gross and microscopic examinations revealed that the decrease of infarct area, inflammation response and collagen deposition in rats given ISO plus curcumin ( P < 0.05). We noted the superior effect of curcumin to reduce the number of apoptotic cardiomyocytes after 9 days. Data point the cardioprotective effect of curcumin to diminish the complication of infarction by the reduction of cell necrosis and apoptosis in a rat model of experimental infarction.     

Designing an immunoinformatic vaccine for peri-implantitis using a structural biology approach

ObjectivesPeri-implantitis is a destructive inflammatory process that affects the soft and hard tissues around dental implants. porphyromonas gingivalis, an anaerobic gram-negative bacterium, appears to be the main culprit. Since there is no efficient and specific vaccine to treat peri-implantitis, the goal of our research has been to develop a multi-epitope vaccination utilizing an immunoinformatics approach that targeted P. gingivalis type I fim A.Materials and methodsP. gingivalis peptides 6JKZ and 6KMF are suitable for vaccine development. B- and T-cell epitopes from 6KMF and 6JKZ were detected and evaluated based on critical factors to produce a multi-epitope vaccine construct. It was assessed based on allergenicity, antigenicity, stability. The vaccine's dual major histocompatibility complex (MHC-I and MHC-II) binding epitopes allowed it to reach a larger population. P. gingivalis fimbriae induce immune subversion through TLR -CXCR4 receptor complex pathway. The ClusPro 2.0 server was used to do the molecular docking using TLR2 - CXCR4 and vaccine epitopes as receptor and ligand respectively.ResultsThe designed vaccine was non-allergenic and had a high antigenicity, solubility, and stability. The 3D structure of the vaccine revealed strong interaction with CXCR4(TLR2) using molecular docking. The vaccine-CXCR4 interface was more consistent, possibly because the vaccination has a higher affinity for the CXCR4-TLR2 complex.ConclusionThis study details the vaccine's distinct and sustained interaction with the CXCR4(TLR2) immunological receptor and its consistent and effective utterance in the bacterial system. As a result, our vaccine formulation will evoke a significant memory response and induce an adaptive immune response against P. gingivalis.     

Self-regulation of pir, a regulatory protein responsible for hyperinduction of pectate lyase in Erwinia chrysanthemi EC16

Previously, we have cloned and characterized the pir (plant inducible regulator) gene, which is responsible for hyperinduction of the synthesis of an isozyme of pectate lyase (PLe) in Erwinia chrysanthemi EC16 in the presence of potato extract and sodium polypectate (NaPP). The Pir protein purified from Escherichia coli overexpressing pir is able to bind to the promoter region of pir as a dimer. Self-regulation of pir by its own translational product (Pir) was suggested from the findings that Pir binds at the promoter region of pir and that the hyperinduction of the pirlux construct in response to plant extract was observed only in pir+ but not in pir mutant EC16. Thus, hyperinduction of PLe was thought to be mainly due to overproduction of Pir. On the other hand, KdgR and PecS, which have been reported to be the major regulatory proteins for the synthesis of pectic enzymes, did not bind to the promoter region of pir. Thus, the regulation of Pir synthesis seems to be independent of KdgR and PecS. Also, its expression was insensitive to catabolite repression as predicted from failure of cyclic AMP (cAMP)-CRP (cAMP recognizing protein) to bind at the pir promoter region.     

Comparison of four synchronization protocols for fixed-time bovine embryo transfer in Bos indicus x Bos taurus recipients

The objective was to evaluate the effects of 400 IU of eCG given on Days 5 or 8 of an estrus synchronization protocol with progesterone-releasing intravaginal devices (PRID) and estradiol benzoate (EB), in recipients for fixed-time embryo transfer. A secondary objective was to determine the effects of injectable progesterone (given concurrent with EB treatment). Three-hundred-and-four crossbred Bos taurus x Bos indicus beef heifers were randomly assigned to one of four treatment groups (2 x 2 factorial design). At unknown stages of the estrous cycle (Day 0), all heifers received a progesterone-releasing intravaginal device (PRID), plus 2mg of EB i.m., with or without a concurrent treatment of 50mg of progesterone i.m. Heifers were further subdivided to receive 0.15 mg of d-cloprostenol (PGF) i.m. and 400 IU of eCG i.m. on Days 5 or 8. In all heifers, intravaginal devices were removed on Day 8 and 1mg of EB was given i.m. on Day 9 (Day 10 was arbitrarily considered the day of estrus). On Day 17, all heifers with >1 CL or a single CL with a diameter > or =18 mm (based on ultrasonographic examination), received an in vitro produced (IVP) embryo by non-surgical transfer. On Day 17, there was an effect of day of eCG administration on the number of CL (1.35 +/- 0.08 versus 1.13 +/- 0.04, for Day 5 versus Day 8, respectively; P = 0.02) and (in a subset of 154 heifers) mean (+/-S.E.M.) plasma progesterone concentrations (2.41 +/- 0.26 versus 1.74 +/- 0.19 ng/mL; P = 0.03). Although the proportion of recipients transferred/treated and pregnant/transferred did not differ among groups, the proportion of recipients pregnant/treated tended (P = 0.1) to be higher in heifers treated with eCG on Day 5 versus Day 8 (47.0% versus 40.7%, respectively). Progesterone treatment had no significant effect. In conclusion, treatment with eCG (and D-cloprostenol) on Day 5 significantly increased the number of CL and plasma progesterone concentrations and tended to increase pregnancy rates, although progesterone treatment had no significant effect.     

'Ethylene-bis[phosphonate] nucleic acids': novel monomeric synthons for the solid-phase synthesis of (P-CH2-CH2-P)-bridged oligonucleotides

An efficient synthesis of modified deoxyribonucleosidic building units, containing the 'ethylene-bisphosphonate nucleic acids' (EBPNAs) 1 or 2, has been developed. By means of solution-phase incorporation of 11, the oxidized form of 2, dinucleotide analogs of type 13 were prepared. The same strategy was used to incorporate 2 into the 5'-terminal position of the 12-mer homopolynucleotide methylphosphonate 14. A preliminary approach for solid-phase incorporation of the nucleosidic building block 1 into a preselected position of an oligonucleotide sequence to give 19 is presented, a reaction performed by means of a coupling strategy involving catalytic oxazaphospholidine-ring cleavage.     

Synthesis of some novel 6-benzyl(or substituted benzyl)-2-beta-D-glucopyranosyl-1,2,4-triazolo[4,3-b][1,2,4]triazines as potential antimicrobial chemotherapeutics

Glucosidation of the new 8-amino-6-benzyl(or substituted benzyl)-2,8-dihydro-1,2,4-triazolo[4,3-b][1,2,4]triazin-7(3H)-ones (3a-d) with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide 4 gave the corresponding N-glucosides 5a-d. Chemical transformations leading to new functionalities have also been achieved to give compounds 7-12. Antimicrobial activity of compounds 5a-c against Aspergillus fumigatus, Penicillium italicum, Syncephalastrum racemosum, Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli is described.     

Synthesis of 6-arylvinyl analogues of the HIV drugs SJ-3366 and Emivirine

This paper reports the synthesis and the antiviral activities of a series of 6-arylvinyl substituted analogues of SJ-3366, a highly potent agent against HIV. The objective was to investigate whether substitution of the 6-arylketone with a 6-arylvinyl group could lead to an improved antiviral activity against HIV-1. The most active compounds 1-ethoxymethyl, 1-(2-propynyloxymethyl), and 1-(2-methyl-3-phenylallyloxymethyl) substituted 6-[1-(3,5-dimethylphenyl)vinyl]-5-ethyl-1H-pyrimidine-2,4-dione (5b, 16, and 18) showed activities against HIV-1 wild type in the range of Efavirenz, and moderate activities against Y181C and Y181C+K103N mutant strains were also observed.     

Frameshift deletion mechanisms in Egyptian Duchenne and Becker muscular dystrophy families

Partial gene deletion is the major type of mutation leading to Duchenne muscular dystrophy (DMD) and its mild allelic form, Becker muscular dystrophy (BMD). Amplification of the genomic DNAs of 152 unrelated dystrophin patients using multiple primers detected 78 (51.3%) probands with deletion mutations. We predicted the translational reading frame for all the deletions in Egyptian dystrophin males. The frameshift rule was confirmed positively ranging for 50 to 67% of the cases depending on the type of disease. We discuss ways of accounting for some exceptions from the frameshift hypothesis in the central and proximal regions. These explanations may help in developing procedures for reducing the severity of dystrophin phenotypes to restore the correct frame by disrupting the translational fidelity. Great efforts have been put into the development of effective 'gene correction' procedures via such intrinsic mechanisms. In addition, we mapped regional difference in deletion mutation frequencies within the DMD gene locus between the different Egyptian governorates. There were no double deletions in the Egyptian dystrophin males.