Synthesis of novel pyrroles and fused pyrroles as antifungal and antibacterial agents

Pyrroles and its fused forms possess antimicrobial activities, they can easily interact with biomolecules of living systems. A series of substituted pyrroles, and its fused pyrimidines and triazines forms have been synthesised, all newly synthesised compound structures were confirmed by spectroscopic analysis. Generally, the compounds inhibited growth of some important human pathogens, the best effect was given by: 2a, 3c, 4d on Gram-positive bacteria and was higher on yeast (C. albicans), by 5c on Gram-negative bacteria and by 5a then 3c on filamentous fungi (A. fumigatus and F. oxysporum). Such results present good antibacterial and antifungal potential candidates to help overcome the global problem of antibiotic resistance and opportunistic infections outbreak. Compound 3c gave the best anti-phytopathogenic effect at a 50-fold lower concentration than Kocide 2000, introducing a safe commercial candidate for agricultural use. The effect of the compounds on DNA was monitored to detect the mode of action.     

Evaluation of low-intensity laser radiation on stimulating the cholesterol degrading activity: Part I. Microorganisms isolated from cholesterol-rich materials

A survey was performed to isolate bacteria and fungi from cholesterol-rich sources including chicken liver, turkey giblets, salmon, lamb, egg yolk, beef brain and shrimps. A total of 34 bacterial and 22 fungal isolates were recovered from the tested sources. The highest count of isolates was recovered from the soil (12 isolates/g), followed by turkey giblets and egg yolk (8 isolates/g, for each). Out of 34 bacterial isolates, five induced the highest level in cholesterol degradation. The most potent bacterial isolate was recovered from turkey giblets and was identified as Streptomyces fradiae. In a trial to increase the cholesterol decomposing potentiality of S. fradiae, low intensity Nd-YAG laser irradiation was evaluated. The exposure of the chlorophyllin – photosensitized bacterium to 210 mW Nd-YAG laser for 8 min induced significant increase in cholesterol degrading activity reaching 73.8% as compared with 54.2% in the case of non-irradiated, non-photosensitized culture. Under the same conditions but using the reaction mixture containing cholesterol as a substrate and extracellular crude enzyme, the percent decomposition reached 53.7% for the irradiated culture as compared to 28.3% in the case of the control. Our data indicate the importance of the photosensitizer in enhancement of laser radiation to stimulate cholesterol decomposition of S. fradiae.     

Control of the dynamics and homeostasis of the Drosophila Hedgehog receptor Patched by two C2-WW-HECT-E3 Ubiquitin ligases

The conserved Hedgehog (HH) signals control animal development, adult stem cell maintenance and oncogenesis. In Drosophila, the HH co-receptor Patched (PTC) controls both HH gradient formation and signalling. PTC is post-translationally downregulated by HH, which promotes its endocytosis and destabilization, but the mechanisms of PTC trafficking and its importance in the control of PTC remain to be understood. PTC interacts with E3 Ubiquitin (UB)-ligases of the C2-WW-HECT family; two of them—SMURF and NEDD4—are known to regulate its levels. We demonstrate that mutation of the PTC PY motif, which mediates binding of C2-WW-HECT family members, inhibits its internalization but not its autonomous and non-autonomous signalling activities. In addition, we show that the two related UB-C2-WW-HECT ligases NEDD4 and SU(DX) regulate PTC trafficking and finely tune its accumulation through partially redundant but distinct functions. While both NEDD4 and SU(DX) promote PTC endocytosis, only SU(DX) is able to induce its lysosomal targeting and degradation. In conclusion, PTC trafficking and homeostasis are tightly regulated by a family of UB-ligases.     

Diabetic Foot Complications and Their Risk Factors from a Large Retrospective Cohort Study

BackgroundFoot complications are considered to be a serious consequence of diabetes mellitus, posing a major medical and economical threat. Identifying the extent of this problem and its risk factors will enable health providers to set up better prevention programs. Saudi National Diabetes Registry (SNDR), being a large database source, would be the best tool to evaluate this problem.MethodsThis is a cross-sectional study of a cohort of 62,681 patients aged ≥25 years from SNDR database, selected for studying foot complications associated with diabetes and related risk factors.ResultsThe overall prevalence of diabetic foot complications was 3.3% with 95% confidence interval (95% CI) of (3.16%–3.44%), whilst the prevalences of foot ulcer, gangrene, and amputations were 2.05% (1.94%–2.16%), 0.19% (0.16%–0.22%), and 1.06% (0.98%–1.14%), respectively. The prevalence of foot complications increased with age and diabetes duration predominantly amongst the male patients. Diabetic foot is more commonly seen among type 2 patients, although it is more prevalent among type 1 diabetic patients. The Univariate analysis showed Charcot joints, peripheral vascular disease (PVD), neuropathy, diabetes duration ≥10 years, insulin use, retinopathy, nephropathy, age ≥45 years, cerebral vascular disease (CVD), poor glycemic control, coronary artery disease (CAD), male gender, smoking, and hypertension to be significant risk factors with odds ratio and 95% CI at 42.53 (18.16–99.62), 14.47 (8.99–23.31), 12.06 (10.54–13.80), 7.22 (6.10–8.55), 4.69 (4.28–5.14), 4.45 (4.05–4.89), 2.88 (2.43–3.40), 2.81 (2.31–3.43), 2.24 (1.98–2.45), 2.02 (1.84–2.22), 1.54 (1.29–1.83), and 1.51 (1.38–1.65), respectively.ConclusionsRisk factors for diabetic foot complications are highly prevalent; they have put these complications at a higher rate and warrant primary and secondary prevention programs to minimize morbidity and mortality in addition to economic impact of the complications. Other measurements, such as decompression of lower extremity nerves, should be considered among diabetic patients.     

Identification of Four Novel Rhipicephalus annulatus Upregulated Salivary Gland Proteins as Candidate Vaccines

The control of Rhipicephalus annulatus ticks in Egypt and other countries relies principally on the application of acaricides which have many drawbacks. Recently, cattle vaccination against ticks showed a potential unconventional approach to control ticks. As a target, salivary glands contain various proteins that may play specific roles during attachment, feeding and may modulate the immune system of the host. We have performed immunoscreening on expression normalized cDNA library to identify unique R. annulatus proteins from salivary gland (RaSal) that are particularly expressed during engorgement. We also present the cloning and sequencing of four novel cDNAs (RaSal1–4) from salivary glands that are expressed during feeding. RaSal4 shows 13 cysteine amino acid residues forming 6 potential disulfide bonds. We detected the expression level of the four genes during embryogenesis in eggs collected at 6, 12 and 18 days after oviposition. RT-PCR analysis detected these proteins at days 12 and 18 while slight amplification was detected at day 6 for only RaSal2. The expression of these salivary genes may put forward new vaccines to control tick infestations and tick-borne diseases.     

Role of RNA Structure Motifs in IRES-Dependent Translation Initiation of the Coxsackievirus B3: New Insights for Developing Live-Attenuated Strains for Vaccines and Gene Therapy

Internal ribosome entry site (IRES) elements are highly structured RNA sequences that function to recruit ribosomes for the initiation of translation. In contrast to the canonical cap-binding, the mechanism of IRES-mediated translation initiation is still poorly understood. Translation initiation of the coxsackievirus B3 (CVB3), a causative agent of viral myocarditis, has been shown to be mediated by a highly ordered structure of the 5′ untranslated region (5′UTR), which harbors an IRES. Taking into account that efficient initiation of mRNA translation depends on temporally and spatially orchestrated sequence of RNA–protein and RNA–RNA interactions, and that, at present, little is known about these interactions, we aimed to describe recent advances in our understanding of molecular structures and biochemical functions of the translation initiation process. Thus, this review will explore the IRES elements as important RNA structures and the significance of these structures in providing an alternative mechanism of translation initiation of the CVB3 RNA. Since translation initiation is the first intracellular step during the CVB3 infection cycle, the IRES region provides an ideal target for antiviral therapies. Interestingly, the 5′ and 3′UTRs represent promising candidates for the study of CVB3 cardiovirulence and provide new insights for developing live-attenuated vaccines.     

Antibacterial activity of a sulfated galactan extracted from the marine alga <Emphasis Type="Italic">Chaetomorpha aerea</Emphasis> against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

The in vitro antimicrobial activity of the marine green algae Chaetomorpha aerea was investigated against gram-positive bacteria, gram-negative bacteria, and a fungus. The water-soluble extract of algae was composed of a sulfated (6.3%) galactan with a molecular weight of 1.160 × 10⁶ Da and a global composition close to commercial polysaccharides, such as dextran sulfate or fucoidan. The polysaccharide was composed of 18% arabinose, 24% glucose, and 58% galactose. The re-suspended extracts (methanol, water) exhibited selective antibacterial activities against 3 gram-positive bacteria including Staphylococcus aureus (ATCC 25923). Minimum inhibitory concentration and minimum bactericidal concentration tests showed that the sulfated galactan could be a bactericidal agent for this strain (40 mg/mL). The results of this study confirmed the potential use of the green algae Chaetomorpha aerea as a source of antibacterial compounds.