Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy

Twenty flavonoid compounds of five different subclasses were selected, and the relationship of their structure to the inhibition of low-density lipoprotein (LDL) oxidation in vitro was investigated. The most effective inhibitors, by either copper ion or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) induction, were flavonols and/or flavonoids with two adjacent hydroxyl groups at ring B. In the presence of the later catechol group, the contribution of the double bond and the carbonyl group at ring C was negligible. Isoflavonoids were more effective inhibitors than other flavonoid subclasses with similar structure. Substituting ring B with hydroxyl group(s) at 2' position resulted in a significantly higher inhibitory effect than by substituting ring A or ring B at other positions. The type of LDL inducer had no effect in flavonoids with catechol structure. Calculated heat of formation data (deltadeltaH(f)) revealed that the donation of a hydrogen atom from position 3 was the most likely result, followed by that of a hydroxyl from ring B. Position 3 was favored only in the presence of conjugated double bonds between ring A to ring B. This study makes it possible to assign the contribution of different functional groups among the flavonoid subclasses to in vitro inhibition of LDL oxidation.     

A mosquito predator survey in Townsville, Australia, and an assessment of Diplonychus sp. and Anisops sp. predatorial capacity against Culex annulirostris mosquito immatures.

A twelve-month survey for mosquito predators was conducted in Townsville, Queensland, Australia, which is located in the arid tropics. The survey revealed the presence of five predaceous insects but only Anisops sp. (backswimmers) and Diplonychus sp. were common. Predatorial capacity and factors influencing this capacity were then assessed for adult Anisops sp. and adult and nymph stages of Diplonychus sp. against Culex annulirostris mosquito immatures under laboratory conditions. Predatorial capacity bioassays showed that adult Diplonychus sp. preyed upon both larval and pupal stages of Cx. annulirostris quite successfully. Nymphs of Diplonychus sp. proved to be more successful with smaller prey immatures, and Anisops sp adults did not prey successfully on any prey pupae. Increasing the foraging area and introducing aquatic vegetation significantly reduced the predatorial capacity of Diplonychus sp. nymphs, while only vegetation and not foraging area had a significant effect on adult Diplonychus sp. predation capacity. Overall, adult Diplonychus sp. proved to be a more efficient predator than Anisops sp., and field trials are now recommended to further assess the potential of Diplonychus sp. as a biocontrol agent.     

Molecular factors regulating E-cadherin expression in urothelial bladder cancer and their correlations with the clinicopathological features

This study aimed to assess the expression of S100A4, Twist and E-cadherin (mRNA and protein) in urothelial bladder cancer, investigate the correlation between them and evaluate their association with the clinicopathological features of the disease. The study included 54 patients diagnosed as urothelial bladder cancer of different stages and grades. The expression levels of S100A4, Twist and E-cadherin (mRNA and protein) in tissue samples were determined by quantitative RT-PCR and immunohistochemistry. The expression of S100A4 and Twist was significantly upregulated while E- cadherin was significantly downregulated in urothelial bladder cancer tissues compared to the adjacent surrounding normal bladder tissues at both mRNA and protein levels (p?<?0.001). Expression levels of S100A4 and Twist were significantly higher in recurrent tumor than in non-recurrent tumors (p?<?0.001) while the expression level of E-cadherin was significantly lower in recurrent tumors than in non-recurrent tumors at both mRNA and protein levels (p?<?0.001). There was a significant positive correlation between S100A4 and Twist expressions (r?=?0.875, p?<?0.001) while significant negative correlations were found between E- cadherin and S100A4 expressions(r=- 0.803, p?<?0.001) and between E-cadherin and Twist (r?=??0.809, p?<?0.001). Up-regulation of S100A4 and Twist and down-regulation of E-cadherin in urothelial bladder cancer tissues compared to adjacent normal tissues were observed. There was a significant negative correlation between S100A4 and E- cadherin and between E- cadherin and Twist expression. However, there was a significant positive correlation between S100A4 and Twist expressions. Furthermore, the alterations in the gene expression were associated with disease stage and grade.     

Mining of Egypt’s Red Sea invertebrates for potential bioactive producers

Objective

The objective of this work was to isolate bacteria from Red Sea invertebrates, determine their antimicrobial activity, and screen for the biosynthetic gene clusters [polyketides (PKs) and nonribosomal peptides (NRPs)] which could be involved in the production of bioactive secondary metabolites.

Result

Eleven different samples of marine invertebrates’ were collected from Egypt’s Red Sea (El-Tor-Sharm El-Sheikh and Hurghada) by scuba diving, and a total 80 isolates of the associated microorganisms were obtained from the cultivation on six different cultural medium. Seven isolates of them showed an antimicrobial activity against five pathogenic reference strains, while the most active antimicrobial agent was isolate number HFF-8 which was 99% identical to Bacillus amyloliquefaciens. HFF-8’s extract showed positive results against Gram negative bacteria, Gram positive bacteria and yeast. Moreover, the isolates gave positive bands when screened for the presence of PK synthase (PKS) I and II and NRP synthetase (NRPS) I and II biosynthetic genes, those biosynthetic fragments when cloned and sequenced were primitively predicted as biosynthetic fragments for kirromycin and leinamycin production by NaPDoS program with 56 and 55%, respectively.

Conclusion

The Red Sea can provide a sustainable solution to combat bacterial resistance. The contribution of this work is that B. amyloliquefaciens was isolated from Heteroxenia fuscescens, Red Sea, Egypt. Moreover, the bacterial extract showed a broad spectrum with a potent antimicrobial activity.

     

Synergistic efficacy of botanical blends with and without synthetic insecticides against Aedes aegypti and Culex annulirostris mosquitoes.

Increasing insecticide resistance requires strategies to prolong the use of highly effective vector control compounds. The use of combinations of insecticides with other insecticides and phytochemicals is one such strategy that is suitable for mosquito control. In bioassays with Aedes aegypti and Culex annulirostris mosquitoes, binary mixtures of phytochemicals with or without synthetic insecticides produced promising results when each was applied at a LC25 dose. All mixtures resulted in 100% mortality against Cx. annulirostris larvae within 24 h rather than the expected mortality of 50%. All mixtures acted synergistically against Ae. aegypti larvae within the first 24 h except for one mixture that showed an additive effect. We conclude that mixtures are more effective than insecticides or phytochemicals alone and that they enable a reduced dose to be applied for vector control potentially leading to improved resistance management and reduced costs.     

Design and synthesis of some thiazolyl and thiadiazolyl derivatives of antipyrine as potential non-acidic anti-inflammatory,analgesic and antimicrobial agents

The synthesis of two groups of structure hybrids comprising basically the antipyrine moiety attached to either polysubstituted thiazole or 2,5-disubstituted-1,3,4-thiadiazole counterparts through various linkages is described. Twelve out of the newly synthesized compounds were evaluated for their anti-inflammatory activity using two different screening protocols; namely, the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays, using diclofenac Na as a reference standard. The ulcerogenic effects and acute toxicity (ALD₅₀) values of these compounds were also determined. Meanwhile, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. Additionally, the synthesized compounds were evaluated for their in vitro antimicrobial activity. In general, compounds belonging to the thiazolylantipyrine series exhibited better biological activities than their thiadiazolyl structure variants. Collectively, compounds 6, 10, 26, and 27 proved to display distinctive anti-inflammatory and analgesic profiles with a fast onset of action. All of the tested compounds revealed super GI safety profile and are well tolerated by the experimental animals with high safety margin (ALD₅₀ > 3.0 g/kg). Meanwhile, compounds 7, 10, 11, and 23 are considered to be the most active broad spectrum antimicrobial members in this study. Compound 10 could be identified as the most biologically active member within this study with an interesting dual anti-inflammatory analgesic and antibacterial profile.     

Impact of Diabetes Mellitus on the Outcome of Pancreatic Cancer

Introduction

Diabetes mellitus (DM) has the potential to impact the pathogenesis, treatment, and outcome of pancreatic cancer. This study evaluates the impact of DM on pancreatic cancer survival.

Methods

We conducted a retrospective cohort study from the Veterans Affairs (VA) Central Cancer Registry (VACCR) for pancreatic cancer cases between 1995 and 2008. DM and no-DM cases were identified from comorbidity data. Univariate and multivariable analysis was performed. Multiple imputation method was employed to account for missing variables.

Results

Of 8,466 cases of pancreatic cancer DM status was known in 4728 cases that comprised this analysis. Males accounted for 97.7% cases, and 78% were white. Overall survival was 4.2 months in DM group and 3.6 months in the no-DM group. In multivariable analysis, DM had a HR = 0.91 (0.849–0.974). This finding persisted after accounting for missing variables using multiple imputations method with the HR in DM group of 0.93 (0.867–0.997).

Conclusions

Our data suggest DM is associated with a reduction in risk of death in pancreatic cancer. Future studies should be directed towards examining this association, specifically impact of DM medications on cancer outcome.     

The effect of C-vacancy on hydrogen storage and characterization of H2 modes on Ti functionalized C60 fullerene A first principles study

Density functional theory calculations were performed to examine the effect of a C vacancy on the physisorption of H₂ onto Ti-functionalized C₆₀ fullerene when H₂ is oriented along the x-, y-, and z-axes of the fullerene. The effect of the C vacancy on the physisorption modes of H₂ was investigated as a function of H₂ binding energy within the energy window (?0.2 to ?0.6 eV) targeted by the Department of Energy (DOE), and as functions of a variety of other physicochemical properties. The results indicate that the preferential orientations of H₂ in the defect-free (i.e., no C vacancy) C₆₀TiH₂ complex are along the x- and y-axes of C₆₀ (with adsorption energies of ?0.23 and ?0.21 eV, respectively), making these orientations the most suitable ones for hydrogen storage, in contrast to the results obtained for defect-containing fullerenes. The defect-containing (i.e., containing a C vacancy) C₅₉TiH₂ complex do not exhibit adsorption energies within the targeted energy range. Charge transfer occurs from Ti 3d to C 2p of the fullerene. The binding of H₂ is dominated by the pairwise support–metal interaction energy E(i)^Cn...Ti, and the role of the fullerene is not restricted to supporting the metal. The C vacancy enhances the adsorption energy of Ti, in contrast to that of H₂. A significant reduction in the energy gap of the pristine C₆₀ fullerene is observed when TiH₂ is adsorbed by it. While the C _n fullerene readily participates in nucleophilic processes, the adjacent TiH₂ fragment is available for electrophilic processes.