47 research outputs found

    Screening And Characterisation Of Inhibitors For Glyoxylate Cycle ICL Enzyme Activity In Candida Albicans

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    Candida albicans is an opportunistic pathogen that causes candidiasis in human. Metabolic pathways have been recently explored as potential antimicrobial targets, for example glyoxylate cycle that enables the C. albicans to servive nutrient-limited niches. Glyoxylate cycle and its key enzymes would be an attractive antifungal drug target for C. albicans. In this study, an alternative cell-based screening approach that better reflect the physiological environment in host system was employed to identify lead compounds that inhibit the glyoxylate cycle

    Transcription Start Site Mapping And Small Regulatory Rna Profiling Of Mycobacterium Tuberculosis

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    Mycobacterium tuberculosis is an actinobacterium that causes chronic infections. Its pathogenesis lies in the thick, lipid-rich cell envelope that facilitate persistence in hostile environments. A refined knowledge of regulatory networks within M. tuberculosis is important to understand its pathogenesis for therapeutic design. Small regulatory RNAs (sRNAs) are key modulatory components within all organisms. Extensive studies over the past decade have uncovered a plethora of bacterial sRNAs, implying that bacterial transcriptomes are far more sophisticated than previously anticipated. Here, sRNA profiles of M. tuberculosis exposed to different stresses were established by analyzing RNA-seq data to address different facets of sRNAome in M. tuberculosis. This study has identified a total of 1,376 sRNA candidates and the subsequent 5’/3’RACE assay has successfully validated a total of five sRNAs, among which predictedRNA_0578 may encode for a novel small peptide and predictedRNA_0020 potentially affects the formation of mycobacterial cell wall. Besides, this study also included transcription start site (TSS) landscapes that provide additional transcriptional features, e.g., promoters and untranslated regions (UTRs). Taken together, this study reveals the complexities of the mycobacterial sRNAome and may facilitate the development of antisense antibiotics

    Evaluation of Palm PCRTM G1-12 System: a portable battery-operated PCR thermal cycler

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    Polymerase chain reaction (PCR) is the basis of recombinant and other molecular biological techniques. Availability of cheap and robust PCR platforms enables the tests to be performed easily, even in resource constrained settings. Herein we compared the efficacy of a portable thermal cycler ( Palm PCRTM G1-12 System) for rapid DNA amplification against the standard Peltier-based thermal cycler using plasmid DNA and genomic DNA in single and multiplex PCR experiments. Our study revealed that the Palm PCRTM G1-12 System could be a portable DNA amplification system to conduct various molecular techniques, especially in places where resources are limited

    Tualang honey improves human corneal epithelial progenitor cell migration and cellular resistance to oxidative stress in vitro

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    Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3 ± 0.4%) were observed compared to the untreated population (20.5 ± 0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells in vitro

    Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

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    Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

    Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry

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    Inhibitors of the glyoxylate cycle enzyme ICL1 in Candida albicans for potential use as antifungal agents.

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    Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1), are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF), rosmarinic acid (ROS), and apigenin (API)) were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis

    Drugs and plant reference compounds used in this study with their PubChem IDs.

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    <p>Drugs and plant reference compounds used in this study with their PubChem IDs.</p

    ADMET properties of potential ICL inhibitors.

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    <p>Abbreviations: BBB (blood-brain barrier); HIA (human intestinal absorption); Caco-2 (Caco-2 permeability); P-gp (P-glycoprotein); ROCT (renal organic cation transporter); CYP450 (cytochrome P450); CYP IP (CYP inhibitory promiscuity); HERG (human ether-a-go-go-related genes); RAT (rat acute toxicity); FT (fish toxicity); TPT (<i>Tetrahymena pyriformis</i> toxicity).</p><p>BBB, HIA, Caco-2, and aqueous solubility indicate the bioavailability of the drug in terms of absorption into the human body; P-gp, CYP450, and CYP IP indicate the metabolism, clearance, and risk of drug-drug interaction with the co-administered drug; ROCT indicates the renal excretion of the drug; HERG indicates the risk of cardiotoxicity caused by the drug; AMES toxicity indicates the risk of carcinogenicity and genotoxicity caused by the drug; RAT, LD<sub>50</sub> is the lethal dosage of drug when tested on mice; FT and TPT are the environmental risk assessments of the drug based on fish and <i>Tetrahymena pyriformis</i> as environmental indicators, respectively.</p
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