114 research outputs found

    Chemical Targeting of GAPDH Moonlighting Function in Cancer Cells Reveals Its Role in Tubulin Regulation

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    SummaryGlycolytic enzymes are attractive anticancer targets. They also carry out numerous, nonglycolytic “moonlighting” functions in cells. In this study, we investigated the anticancer activity of the triazine small molecule, GAPDS, that targets the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDS showed greater toxicity against cancer cells compared to a known GAPDH enzyme inhibitor. GAPDS also selectively inhibited cell migration and invasion. Our analysis showed that GAPDS treatment reduced GAPDH levels in the cytoplasm, which would modulate the secondary, moonlighting functions of this enzyme. We then used GAPDS as a probe to demonstrate that a moonlighting function of GAPDH is tubulin regulation, which may explain its anti-invasive properties. We also observed that GAPDS has potent anticancer activity in vivo. Our study indicates that strategies to target the secondary functions of anticancer candidates may yield potent therapeutics and useful chemical probes

    Biomass degradation : Challenges and strategies in extraction and fractionation of hemicellulose

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    Extraction and fractionation of hemicellulose from complex lignocellulosic biomass are crucial steps to acquiring purified hemicellulose that can probably used in biofuel and biochemical sectors. Yet, several challenges have impeded for obtaining the hemicellulose fraction as it involves the complexity of extracting and fractioning hemicellulose. In this study, the authors have discussed the outline of the most prospective and effective method for separation, extraction, and purification of hemicellulose-rich biomass. A current overview of challenges and problems in hemicellulose separation was addressed. Subsequently, the influence of heterogeneous biomass types, cultivation and harvesting times, accessible surface areas, acetyl and other functional groups on purity was observed. On the other hand, several proper strategies efficiently employed in hemicellulose extraction and fractionation are provided. The biochemical process gives a highly positive contribution to sustaining hemicellulose-based bioproducts. Biological pre-treatment of lignocellulose using enzymes and bacteria is convinced as the most effective and efficient method to reduce the lignin content and to improve the purity due to less inhibitory and minimal coke formation. Saccharomyces cerevisiae has been widely used in the hemicellulose-based bioprocess due to resulting in high conversion (>80%) and yield (>70%). The hydrothermal method followed by multistep ultrafiltration treatment generated the highest hemicellulose purity (100%) and by-product removal (94.4–99.2 wt%). Comprehensive strategies for hemicellulose extraction and fractionation involving biological and non-biological treatments are also the highlights of this article

    Microbial biotechnology approaches for conversion of pineapple waste in to emerging source of healthy food for sustainable environment

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    One of the most significant and difficult jobs in food sustainability, is to make use of waste in the vegetable and fruit processing sectors. The discarded fruits along with their waste materials, is anticipated to have potential use for further industrial purposes via extraction of functional ingredients, extraction of bioactive components, fermentation. As a result of its abundant availability, simplicity and safe handling, and biodegradability, pineapple waste is now the subject of extensive research. It is regarded as a resource for economic development. This vast agro-industrial waste is being investigated as a low-cost raw material to produce a variety of high-value-added goods. Researchers have concentrated on the exploitation of pineapple waste, particularly for the extraction of prebiotic oligosaccharides as well as bromelain enzyme, and as a low-cost source of fibre, biogas, organic acids, phenolic antioxidants, and ethanol. Thus, this review emphasizes on pineapple waste valorisation approaches, extraction of bioactive and functional ingredients together with the advantages of pineapple waste to be used in many areas. From the socioeconomic perspective, pineapple waste can be a new raw material source to the industries and may potentially replace the current expensive and non-renewable sources. This review summarizes various approaches used for pineapple waste processing along with several important value-added products gained which could contribute towards healthy food and a sustainable environment

    Two-Year clinical outcomes after coronary bifurcation stenting in older patients from Korea and Italy

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    BackgroundOlder patients who treated by percutaneous coronary intervention (PCI) are at a higher risk of adverse cardiac outcomes. We sought to investigate the clinical impact of bifurcation PCI in older patients from Korea and Italy.MethodsWe selected 5,537 patients who underwent bifurcation PCI from the BIFURCAT (comBined Insights from the Unified RAIN and COBIS bifurcAtion regisTries) database. The primary outcome was a composite of target vessel myocardial infarction, clinically driven target lesion revascularization, and stent thrombosis at two years.ResultsIn patients aged ≥75 years, the mean age was 80.1 ± 4.0 years, 65.2% were men, and 33.7% had diabetes. Older patients more frequently presented with chronic kidney disease (CKD), severe coronary calcification, and left main coronary artery disease (LMCA). During a median follow-up of 2.1 years, older patients showed similar adverse clinical outcomes compared to younger patients (the primary outcome, 5.7% vs. 4.5%; p = 0.21). Advanced age was not an independent predictor of the primary outcome (p = 0.93) in overall patients. Both CKD and LMCA were independent predictors regardless of age group.ConclusionsOlder patients (≥75 years) showed similar clinical outcomes to those of younger patients after bifurcation PCI. Advanced age alone should not deter physicians from performing complex PCIs for bifurcation disease

    Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data

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    Background/AimsWhile gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.MethodsThe data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.ResultsThe initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).ConclusionsThe clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis
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