In Silico Analysis Reveals High Levels of Genetic Diversity of Plasmodium knowlesi Cell Traversal Protein for Ookinetes and Sporozoites (PkCelTOS) in Clinical Samples.

The cell-traversal protein for ookinetes and sporozoites (CelTOS), expressed on the surface of ookinetes and sporozoitesin Plasmodium species, is a promising malaria vaccine candidate. CelTOS is essential for parasite invasion into mosquito midgut and human hepatocytes, thereby contributing to malaria transmission and disease pathogenesis. This study explores the genetic diversity, polymorphisms, haplotypes, natural selection, phylogenetic analysis, and epitope prediction in the full-length Plasmodium knowlesi CelTOS gene in clinical samples from Sarawak, Malaysian Borneo, and long-term laboratory strains from Peninsular Malaysia and the Philippines. Our analysis revealed a high level of genetic variation in the PkCelTOS gene, with a nucleotide diversity of π ~ 0.021, which was skewed towards the 3' end of the gene. This level of diversity is double that observed in PfCelTOS and 20 times that observed in PvCelTOS from worldwide clinical samples. Tests of natural selection revealed evidence for positive selection within clinical samples. Phylogenetic analysis of the amino acid sequence of PkCelTOS revealed the presence of two distinct groups, although no geographical clustering was observed. Epitope prediction analysis identified two potential epitopes (96AQLKATA102 and 124TIKPPRIKED133) using the IEDB server and one epitope (125IKPPRIKED133) by Bcepred server on the C' terminal region of PkCelTOS protein. Both the servers predicted a common epitope region of nine amino acid length (IKPPRIKED) peptide, which can be studied in the future as a potential candidate for vaccine development. These findings shed light on the genetic diversity, polymorphism, haplotypes, and natural selection within PkCelTOS in clinical samples and provide insights about its future prospects as a potential candidate for P. knowlesi malaria vaccine development.

Optimization of different growth parameters for maximum production of bioactive crude metabolites by Aspergillus fumigatus.

Aspergillus fumigatus is a green echinulate with greenish phialides and 2.5-3 mm conidia. The diverse biological functions of A. fumigatus secondary metabolites make them interesting. The ethyl acetate extract of A. fumigatus was tested for antibacterial activity. Culture media, temperature, incubation and pH were optimized for A. fumigatus growth. Continuous 150rpm agitation incubated the fungus at 28°C for 10 days. Potato Dextrose Broth at 28°C in shaking incubator at pH 04 produced the most biomass and secondary metabolites. Metabolite antibacterial activity was tested. Salmonella flexneri had the greatest zone of inhibition at 100µl (25.66mm) while Staphylococcus aureus had the least (16.33mm). At 75µg/mL, S. flexneri showed 23.66mm activity and S. typhi 14.66mm. At 50µg/mL, S. flexneri was 21.33mm and S. typhi 12.33mmMBC was 0.01µg/µl and MIC50 varied. At 100µg/mL, the metabolites showed antifungal efficacy against Penicillium chrysogenum (26.33mm) but not A. flavus (21.33mm). A. oryzae was significantly inhibited at 75µg/mL (26.33mm) and 50µg/mL (20.33mm). 1000µl demonstrated 100% phytotoxicity, 100µl 60% and 10µl 50%. Bactrocera cucurbitae, Sitotroga cerealella and Callosobruchus maculatus were killed at 150, 100 and 75µl. Metabolites and antibiotics synergized well. Metabolites have alkanes, esters and ethers in their infrared spectra.

Antibiotic susceptibility and bioremediation potential of probiotic bacteria against lead and cadmium isolated from yogurt.

Probiotic bacteria have capacity to bind with heavy metals. The present study was planned to assess the bioremediation potential of probiotic Lactobacillus species isolated from yogurt samples. L. acidophilus and L. plantarum were tested for acidic pH tolerance, bile salt resistance and gastric juice tolerance. The antibiotic susceptibility and antimicrobial activity was also checked. These Lactobacillus species were also evaluated for degradation of lead (Pb) and cadmium (Cd) metals. The results indicated that L. acidophilus and L. plantarum were able to tolerate high acidic pH: 3. both showed significant growth after exposure to stimulated gastric juice from 0 to 24 hours. The significant plate count was observed at different bile salt concentrations (0.1%, 0.3%). The isolates showed resistance for all the tested antibiotics except L. acidophilus showed susceptibility for gentamicin and co-amoxiclave. The isolates depicted no antimicrobial activity against the indicator bacteria. L. acidophilus and L. plantarum were capable of tolerating Cd and Pb. Maximum tolerance and removal were observed for Pb by both Lactobacillus spp. The Cd removal was 11.50 and 3.50% while Pb removal was 42.70 and 35.50% for L. plantarum and L. acidophilus, respectively. In conclusion, L. acidophilus and L. Plantarum have potential for bioremediation of heavy metals.

Quercetin as a Dietary Supplementary Flavonoid Alleviates the Oxidative Stress Induced by Lead Toxicity in Male Wistar Rats.

Quercetin is a naturally existing plant pigment belonging to the flavonoid group; it is contained in a wide range of vegetables and fruits. The accumulated evidence points to the potential uses of quercetin in protection of some disease conditions. Lead is one of the highly toxicant heavy metals that are widely spread in the environment and implicated in a wide spectrum of industries. No previous study has been reported to evaluate the effect of quercetin on lead toxicity. Therefore, the present study was conducted to elucidate some aspects of quercetin bioactivities in regard to its ability to combat the oxidative stress induced by lead toxicity. For this purpose, a total of sixty male Wistar rats were randomly and equally divided into three groups of 20 animals each; untreated control animals (group 1), lead-exposed animals (group 2; exposed to lead daily by oral gavage at the dose of 80 mg/Kg b.w.), and group 3 of animals, which were exposed to lead and daily received quercetin (10 h gap time between lead exposure and the receiving of quercetin) by oral gavage at the dose of 350 mg/Kg b.w. The experiment period was 8 weeks. All the assayed hematological and biochemical parameters of animals exposed to lead were significantly altered compared with the untreated control levels. Animals exposed to lead (group 2) exhibited significant decrements of the erythrocytic and total leucocytic counts, hemoglobin concentration, packed cell volume percent, total proteins, albumin and globulin. These animals also disclosed significantly decreased levels of antioxidant markers including total thiols, catalase and glutathione. On the other hand, these animals demonstrated significant increments in the levels of bilirubin, urea, creatinine, BUN, serum enzymes, H2O2 and MDA. Animals exposed to lead and given quercetin (group 3) exhibited improvement of these parameters, which were brought back at varying degrees toward the untreated control levels. Basing on the improvements of the assayed hematological and biochemical parameters, it was concluded that quercetin as a dietary supplement can act efficiently as an antioxidant to counteract the oxidative stress induced by lead toxicity and to maintain the oxidant antioxidant balance.

Mosquito larvicidal activity of pyrrolidine-2,4-dione derivatives: An investigation against Culex quinquefasciatus and molecular docking studies.

The pyrrolidine-2,4-dione derivatives were used to conduct a larvicidal test on Culex quinquefasciatus larvae of the second instar. Mannich base condensation method was used to synthesis the pyrrolidine-2,4-dione derivatives by grindstone method. The reaction conditions were mild, resulting in high yields. An analysis of the synthesized compounds was carried out using FTIR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. Synthesized compounds (1a-h) were evaluated for larvicidal activities. Compound 1e (LD50: 26.06 µg/mL), and 1f (LD50: 26.89 µg/mL), and were notably more active against Culex quinquefasciatus than permethrin (LD50: 26.14 µg/mL). The docking studies also demonstrated that 1e, and 1f are potent larvicides with higher binding energy (-12.6 kcal/mol) than the control in the mosquito odorant binding protein (PDB ID: 3OGN). The larvicidal properties of lead molecules have made them important for use as insecticides.

Synthesis, structural characterization, and DFT studies of anti-cancer drug N-(2-Aminophenyl)-2-(4-bromophenoxy)acetamide.

Drug design is an integrated and developing system that portends an era of a novel and safe tailored drugs. It involves studying the effects of biologically active synthetic, semi-synthetic, and natural compounds based on molecular interactions in terms of molecular structure with activated functional groups or its unique physicochemical properties involved. The title compound, N-(2-aminophenyl)-2-(4-bromophenoxy) acetamide (c), was synthesized in a good yield and characterized by different spectroscopic techniques (1H, 13CNMR, and LC-MS) and finally, the structure was confirmed by X-ray diffraction (XRD) studies. The XRD data confirms that the cryatal structure is orthorhombic with space group of Pca2 1 . The intermolecular interactions (N-H … O and N-H … Cg) inside the molecule stabilizes the crystal structure. The existence of this intermolecular interactions are computed by the Hirshfeld surfaces (HS) and two-dimensional (2D) fingerprints plot analysis. In addition to this, Energy frame work analysis is performed to quantify the interaction energies between the molecular pairs in a crystal by incorporating new version of CrystalExplorer17 using the energy model of HF/3-21G. Also to calculate the HOMO and LUMO energies, DFT calculations were carried out.

Impact of Ramadan-focused diabetes education on hypoglycemia risk and metabolic control for patients with type 2 diabetes mellitus: A systematic review.

BACKGROUND: Ramadan fasting is regarded as a form of worship amongst Muslims. However, patients with a high risk of diabetic complications are advised to avoid fasting, as the practice is associated with significant impacts on several health factors for type 2 diabetic patients, including glycaemic control. Thus, a lack of focused education before Ramadan may result in negative health outcomes. AIM: To evaluate the impact of a Ramadan-focused diabetes education programme on hypoglycaemic risk and other clinical and metabolic parameters. METHODS: A systematic literature search was performed using Scopus, PubMed, Embase, and Google Scholar to identify relevant studies meeting the inclusion criteria from inception. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and guidelines were followed when performing the search and identification of appropriate studies. RESULTS: Seventeen studies were included in this systemic review; five of them met the criteria to compile for a meta-analysis. The included studies were with various study designs, including randomised controlled trials, quasi-experimental and non-randomised studies. Overall, the results revealed a significant reduction of hypoglycemia risk (81% reduction) for fasting patients in intervention groups who received Ramadan-focused education compared with patients receiving conventional care (OR 0.19, 95% CI: 0.08-0.46). Moreover, HbA1c significantly improved amongst patients who received a Ramadan-focused diabetes education intervention, compared with those receiving conventional care. CONCLUSION: Ramadan-focused diabetes education had a significant impact on hypoglycemia and glycaemic control, with no significant effect on body weight, blood lipids or blood pressure.

Xanthone Conjugated Amino Acids as Potential Anticancer and DNA Binding Agents: Molecular Docking, Cytotoxicity and SAR Studies.

BACKGROUND: Amino acids conjugated with heterocyclic molecules are well known for their effective bioactive properties. In search of effective anticancer agents, a series of xanthone linked amino acids 2-23 were synthesized and tested for in vitro anticancer activity. METHODS: In vitro anticancer activity of the synthesized xanthone linked amino acids 2-23 are tested against three different cancer cell lines MCF-7, MDA-MB-435 and A549 by MTT assay and validated by DNA binding and molecular docking approaches. Doxorubicin and ethidium bromide used as standard and positive control respectively. RESULTS: Compounds 7, 8 and 9 exhibited potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green. In the molecular docking study, binding interactions of the most active compounds 7, 8 and 9 were confirmed to molecular surface of DNA. CONCLUSION: Structure-Activity Relationship (SAR) showed that the aromatic and hydrophobic amino acids (phenylalanine, tyrosine, and tryptophan) favoured the DNA binding studies and anticancer activity whereas, aliphatic amino acids showed least anticancer activity.

Role of BP*C@AgNPs in Bap-dependent multicellular behavior of clinically important methicillin-resistant Staphylococcus aureus (MRSA) biofilm adherence: A key virulence study.

Bacterial adhesion is a threshold event in the formation of biofilms which leads to serious bacterial diseases. This shows that the underlining the problem is interesting and need to solve the problem of biofilm-related complications. To support this, in the present study, we first time initiated to understand the role of methicillin-resistant Staphylococcus aureus (MRSA) biofilm using previously developed benzodioxane midst piperazine decorated chitosan silver nanoparticles (BP*C@AgNPs). The BP*C@AgNPs studied for antimicrobial, anti-biofilm, biofilm adherence inhibition, the role of ions in biofilm, and an antibiotic cocktail in the treatment of biofilm was assessed. The results showed that, the significant biocidal role of BP*C@AgNPs in controlling the MRSA biofilm and interaction of biofilm protein to calcium ions were significantly decreased. This confirms that calcium ion involved in the biofilm formation and for the treatment of BP*C@AgNPs, cocktail of enzyme and antibiotic have the promising therapeutic value was observed. In future the locking of biofilm protein and its expression in presence of calcium ion was interesting, and greater application related to biofilm infection was warrantable.

CD58; leucocyte function adhesion-3 (LFA-3) could be used as a differentiating marker between immune and non-immune thyroid disorders.

The link between Graves' disease (GD) and Hashimoto's thyroiditis (HT) has been debated for decades due to the shared pathological and immunological components. Immune intolerance and inappropriate immune reaction against self-thyroid cells are distinctive features of both diseases, but definitive data for the clinical presentation of autoimmune thyroid disease remains unclear. To analyse the expression of T-regulatory cells, CD58, the CD4/CD8 ratio and the neutrophil/lymphocyte ratio and to determine if these parameters could be used as differentiating markers between auto- and non-immune thyroid diseases, 75 patients were enrolled in this study-40 with autoimmune thyroid disease (HT and GD ), 15 with non-immune thyroid disease, and 20 healthy controls. Multicolour flow cytometry was used to analyse CD58, T-regulatory cells (Treg) expressing CD4, CD25, HLA-DR and CD8 using different stained fluorescent labelled monoclonal antibodies. The neutrophils and lymphocyte ratio was also measured. Lower expression of Treg with higher expression of CD58 (LFA-3) was found in the autoimmune diseases when compared with the non-immune and control groups. ROC analysis showed that CD58 with sensitivity 88% and specificity 100% with cut-off value more than or equal to 29.9 indicates Hashimoto's disease, while lower value indicates colloid goitre, and higher or equal to 29.84 indicates Graves' disease and lower indicates colloid goitre with 100% sensitivity and specificity. CD58 could be used as differentiating marker between immune and non-immune thyroid disorders.

A Newly Developed mm-Wave Sensor for Detecting Plaques of Arterial Vessels.

BACKGROUND: Microcalcifications within the fibrous cap of the arteriosclerotic plaques lead to the accrual of plaque-destabilizing mechanical stress. New techniques for plaque screening with small detectors and the ability to differentiate between the smooth and hard elements of plaque formation are necessary. METHOD: Vascular plaque formations are characterized as calcium phosphate containing structures organized as hydroxylapatite resembling the mineral whitlockite. In transmission and reflexion studies with a simple millimeter wave (mm-wave)-demonstrator, we found that there is a narrow window for plaque detection in arterial vessels because of the tissue water content, the differentiation to fatty tissue, and the dielectric property of air or water, respectively. RESULT: The new sensor is based on a sensing oscillator working around 27 GHz. The open-stub capacitance determines the operating frequency of the sensor oscillator. The capacitance depends on the dielectric properties of the surrounding material. The sensor components were completely built up in surface mount technique. CONCLUSION: Completed with a catheter, the sensor based on microwave technology appears as a robust tool ready for further clinical use.

The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases.

Neoplastic metastasis is a major process where tumor cells migrate from the primary tumor and colonize at other parts of our body to form secondary tumor. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related deaths. In the current examination, a novel series of pyridazine analogues 6a-l was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Also, compound 6j proved its potentiality against Dalton's solid lymphoma progression in-vivo by abridging MVD and MMP expressions. Compound 6j interacts with MMP-2 and MMP-9 by H- bond in-silico, thereby down regulates the MMPs action in tumourigenesis. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9 and thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent.

CD235a (Glycophorin-A) Is the Most Predictive Value Among Different Circulating Cellular Microparticles in Thrombocytopenic Human Immunodeficiency Virus Type 1.

BACKGROUND: This study was conducted to assess different cellular microparticles (MPs) in thrombocytopenic human immunodeficiency virus type 1 and their significance as disease activity markers. METHODS: Thirty-five thrombocytopenic human immunodeficiency diseases and 25 healthy controls with matched age and sex were selected. Viral load was quantitated by COBAS real-time polymerase reaction (PCR) assessment of absolute T-cell subsets CD4, CD8 as a disease progress marker. Platelet MPs, platelet-derived monocyte MPs (CD42a, CD61), erythrocyte MP (CD235a), monocytic MP (CD14), and platelet activity MPs (CD62P, PAC-1) were assessed by multicolor flow cytometry FACSCalibur, while platelet functions were assessed by platelet function analyzer (PFA-100). CD42a, CD61, and platelet activity index represented by PAC-1 and CD62. RESULTS: P-selectin in HIV-infected patient samples were significantly greater (P < 0.001) than among controls. There was a negative correlation between the proportion of PAC-1 and CD62 P-selectin-positive MPs and levels of CD4(+) T-cell counts (r = -0.403, P = 0.016; r = -0.438, P = 0.008), respectively. There was a negative correlation between collagen-ADP and levels of CD4(+) T-cell counts (r = -0.368, P = 0.03). There was a significant high expression level of CD14 monocyte MPs in patients than controls (P < 0.0001), overexpression of CD235a (P < 0.0001), and no correlation between CD14 and CD4, whereas there was a significant negative correlation with CD235a (r = -0.394, P = 0.019). A linear regression analysis of CD4 as a disease progression marker with other variable indicators in HIV patients showed that CD235a could be the most sensitive predictor similar to CD4. CONCLUSION: Different cellular MPs and platelets activated in HIV patients could have a role in thrombotic events in these patients.

Biochemical evaluation of hyaluronic acid in breast cancer.

BACKGROUND: The latest experimental studies on human cancer diseases have observed the bioactive role of hyaluronic acid (HA) during carcinogenesis. HA is a component of the extra-cellular matrix (ECM). It is closely correlated with tumor cell growth, proliferation, and metastasis. The present study aimed to evaluate the biochemical role of HA and its degrading enzymes and products in breast cancer (BC) patients under therapy treatment. METHODS: An ELISA method was used to determine HA levels and standard spectrophotometric techniques were used to estimate the activities of HA degrading enzymes hyaluronidase (HAS), N-acetyl-beta-D-glucosminidase (NAG), and beta-glucuronidase (beta-Glu) and the concentration of both glucoseamine (G-Amine) and glucuronic acid (GA) as degrading products in blood sera of 50 BC patients before and after chemotherapy treatment and in blood sera of 40 healthy women as controls. Statistical analyses were performed by a statistical package for social sciences (SPSS, version 15.0). RESULTS: Elevated serum HA levels, increased HAS, NAG, and beta-Glu activities and high concentrations of G-Amine and GA were significantly found (p < 0.001) in patients before treatment compared to controls. After all BC patients had received the first chemotherapy course, HA and its previous degrading parameters were significantly decreased (p < 0.001) in post-treated patients compared to pre-treated patients. CONCLUSIONS: Hyaluronic acid and its degrading enzymes and products can be considered a biomarker for early detection of recurrent disease and also for monitoring the effective therapeutic follow up of BC patients.

Surface charge of polymer particles in water: the role of ionic end-groups.

Polymer particles, containing macromolecules made by the polymerization of nonionic monomers, can be ionized in water thanks to the end-groups of the macromolecules. We show that poly(methylmethacrylate) particles with ionic end-groups can acquire colloidal properties such as dispersion metastability and electrokinetic mobility. We demonstrate that the variation of these colloidal properties according to solution pH is uniquely determined by the chemical nature of the end-groups and therefore by the nature of the initiator used in the polymerization reaction. We compare polymer dispersions in which the polymer particles were made by different processes (e.g., surfactant-free emulsion polymerization or precipitation of the macromolecules induced by solvent shifting). For each colloidal dispersion, we determine the number of end-groups that are actually located at the surfaces of the particles, and we show that this number is a trace of the process by which the macromolecules were self-assembled into colloidal particles. We propose that it is possible to recover mechanistic details of this self-assembly process through measurements of the distribution of end-groups within the particles.

Blood chemical changes and renal histological alterations induced by gentamicin in rats.

Gentamicin is an effective widely used antibiotic, but the risk of nephrotoxicity and oxidative damage limit its long-term use. Hence, the current study aims to elucidate such hazardous effects. To achieve the study aim male Wistar albino rats (Rattus norvegicus) were exposed to gentamicin to investigate the resultant blood chemical changes and renal histological alterations. In comparison with control rats, gentamicin produced outstanding tubular, glomerular and interstitial alterations that included degeneration, necrosis, cytolysis and cortical tubular desquamation together with mesangial hypercellularity, endothelial cell proliferation and blood capillary congestion. Compared with control animals significant blood chemical changes (P < 0.05) including free radicals, ALT, AST, ALP, serum creatinine and serum urea were recorded in gentamicin-injected animals. The findings revealed that exposure to gentamicin can induce significant histological alterations in the kidney as well as remarkable blood chemical changes that might indicate marked renal failure.

Integrating spatial data and shorebird nesting locations to predict the potential future impact of global warming on coastal habitats: A case study on Farasan Islands, Saudi Arabia.

One of the expected effects of the global warming is changing coastal habitats by accelerating the rate of sea level rise. Coastal habitats support large number of marine and wetland species including shorebirds (plovers, sandpipers and allies). In this study, we investigate how coastal habitats may be impacted by sea level rise in the Farasan Islands, Kingdom of Saudi Arabia. We use Kentish plover Charadrius alexandrinus - a common coastal breeding shorebird - as an ecological model species to predict the influence of sea level rise. We found that any rise of sea level is likely to inundate 11% of Kentish plover nests. In addition, 5% of the coastal areas of Farasan Islands, which support 26% of Kentish plover nests, will be flooded, if sea level rises by one metre. Our results are constrained by the availability of data on both elevation and bird populations. Therefore, we recommend follow-up studies to model the impacts of sea level rise using different elevation scenarios, and the establishment of a monitoring programme for breeding shorebirds and seabirds in Farasan Islands to assess the impact of climate change on their populations.

Urinary tract infection and adverse outcome of pregnancy.

UNLABELLED: Urinary tract infections (UTIs) during pregnancy are among the commonest health problems world wide, specially in developing countries, including Egypt. It has several adverse outcomes not only on the mother but also on the fetus as well.. The aim of this study is to determine the incidence of UTIs during pregnancy, study the main risk factors associated with such infections and find the impact of these infections on some pregnancy outcomes namely the gestational age and birth weight. A follow-up study on 249 pregnant women attending the ante natal care clinic at Zagazig university hospital. They were recruited over a period from 1st of September to 30th of or November, 2005. The outcome could be recorded for 201 of them. Data were collected through a pretested questionnaire, repeated urine analyses and recording of outcome of pregnancy. The study revealed that the incidence of UTIs during pregnancy was 31.3%. The commonest organisms were Klebsiella and E-coli. Several socio-demographic characteristics were found significantly associated with UTIs, age being 30 years and more, illiterates and low educational level, low socio-economic level and those with unsatisfactory personal hygiene and those using underwear clothes other than cotton. Significant associations with UTIs were also found in multigravidae 4th and more, those having more than one child and those who previously suffered UTIs. The only predicting variable with UTIs was low socio-economic level. The study revealed that the probability of delivering premature infants and low birth weights was significantly higher among those who experienced UTIs during pregnancy. Multivariate analysis revealed that UTI was one of the main contributors to pre-mature deliveries. CONCLUSION AND RECOMMENDATIONS: Urinary tract infections with pregnancy still constitute a big problem with high incidence. It has a great impact on pregnancy outcome mainly pre-mature labor. So, the study recommends health education about personal hygiene, repeated urine cultures early in pregnancy and during the third trimesters, specially for low socio-economic pregnant women. Specific antibiotics should be prescribed to avoid adverse pregnancy outcome.