Epigallocatechin-3-Gallate (EGCG), a Green Tea Polyphenol,Stimulates Hepatic Autophagy and Lipid Clearance

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has been shown to have anti-inflammatory, anti-cancer, anti-steatotic effects on the liver. Autophagy also mediates similar effects; however, it is not currently known whether EGCG can regulate hepatic autophagy. Here, we show that EGCG increases hepatic autophagy by promoting the formation of autophagosomes, increasing lysosomal acidification, and stimulating autophagic flux in hepatic cells and in vivo. EGCG also increases phosphorylation of AMPK, one of the major regulators of autophagy. Importantly, siRNA knockdown of AMPK abrogated autophagy induced by EGCG. Interestingly, we observed lipid droplet within autophagosomes and autolysosomes and increased lipid clearance by EGCG, suggesting it promotes lipid metabolism by increasing autophagy. In mice fed with high-fat/western style diet (HFW; 60% energy as fat, reduced levels of calcium, vitamin D3, choline, folate, and fiber), EGCG treatment reduces hepatosteatosis and concomitantly increases autophagy. In summary, we have used genetic and pharmacological approaches to demonstrate EGCG induction of hepatic autophagy, and this may contribute to its beneficial effects in reducing hepatosteatosis and potentially some other pathological liver conditions.     

Proteomic analysis reveals USP7 as a novel regulator of palmitic acid-induced hepatocellular carcinoma cell death

Nutrient surplus and consequent free fatty acid accumulation in the liver cause hepatosteatosis. The exposure of free fatty acids to cultured hepatocyte and hepatocellular carcinoma cell lines induces cellular stress, organelle adaptation, and subsequent cell death. Despite many studies, the mechanism associated with lipotoxicity and subsequent cell death still remains poorly understood. Here, we have used the proteomics approach to circumvent the mechanism for lipotoxicity using hepatocellular carcinoma cells as a model. Our quantitative proteomics data revealed that ectopic lipids accumulation in cells severely affects the ubiquitin-proteasomal system. The palmitic acid (PA) partially lowered the expression of deubiquitinating enzyme USP7 which subsequently destabilizes p53 and promotes mitotic entry of cells. Our global phosphoproteomics analysis also provides strong evidence of an altered cell cycle checkpoint proteins’ expression that abrogates early G2/M checkpoints recovery with damaged DNA and induced mitotic catastrophe leading to hepatocyte death. We observe that palmitic acid prefers apoptosis-inducing factor (AIF) mediated cell death by depolarizing mitochondria and translocating AIF to the nucleus. In summary, the present study provides evidence of PA-induced hepatocellular death mediated by deubiquitinase USP7 downregulation and subsequent mitotic catastrophe.Subject terms: Apoptosis, Protein-protein interaction networks     

Fermentation of biomass-generated producer gas to ethanol

The development of low-cost, sustainable, and renewable energy sources has been a major focus since the 1970s. Fuel-grade ethanol is one energy source that has great potential for being generated from biomass. The demonstration of the fermentation of biomass-generated producer gas to ethanol is the major focus of this article in addition to assessing the effects of producer gas on the fermentation process. In this work, producer gas (primarily CO, CO(2), CH(4), H(2), and N(2)) was generated from switchgrass via gasification. The fluidized-bed gasifier generated gas with a composition of 56.8% N(2), 14.7% CO, 16.5% CO(2), 4.4% H(2), and 4.2% CH(4). The producer gas was utilized in a 4-L bioreactor to generate ethanol and other products via fermentation using a novel clostridial bacterium. The effects of biomass-generated producer gas on cell concentration, hydrogen uptake, and acid/alcohol production are shown in comparison with "clean" bottled gases of similar compositions for CO, CO(2), and H(2). The successful implementation of generating producer gas from biomass and then fermenting the producer gas to ethanol was demonstrated. Several key findings following the introduction of producer gas included: (1) the cells stopped growing but were still viable, (2) ethanol was primarily produced once the cells stopped growing (ethanol is nongrowth associated), (3) H(2) utilization stopped, and (4) cells began growing again if "clean" bottled gases were introduced following exposure to the producer gas.     

Doppler ultrasound scoring to predict chemotherapeutic response in advanced breast cancer

Background

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disease. It is relatively recent that type 2C was identified as a separate group solely presenting with pheochromocytomas. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. It proved to be the first manifestation of bilateral pheochromocytomas. The family history may indicate the diagnosis, but only identification of a germ line mutation in the DNA of a patient will confirm carriership.

Case presentation

A 27 year pregnant patient with intra uterine growth retardation presented with hypertension and pre-eclampsia. Magnetic resonance imaging revealed bilateral adrenal pheochromocytoma. She underwent laparoscopic adrenelectomy and a missense mutation (Gly93Ser) in exon 1 of the VHL gene on chromosome 3 (p25 - p26) was shown in the patient, her father and her daughter confirming the diagnosis of VHL.

Conclusion

In almost all VHL families molecular genetic analysis of DNA will demonstrate an inherited mutation. Because of the involvement in several organs, periodic clinical evaluation should take place in a well coordinated, multidisciplinary setting. VHL disease can be classified into several subtypes. VHL type 2C patients present with pheochromocytomas without evidence of haemangioblastomas in the central nervous system and/or retina and a low risk of renal cell carcinoma. Therefore, in such families, periodic clinical screening can be focussed on pheochromocytomas.     

Botryococcus braunii: A Renewable Source of Hydrocarbons and Other Chemicals

ABSTRACT:?

Botryococcus braunii, a green colonial microalga, is an unusually rich renewable source of hydrocarbons and other chemicals. Hydrocarbons can constitute up to 75% of the dry mass of B. braunii. This review details the various facets of biotechnology of B. braunii, including its microbiology and physiology; production of hydrocarbons and other compounds by the alga; methods of culture; downstream recovery and processing of algal hydrocarbons; and cloning of the algal genes into other microorganisms. B. braunii converts simple inorganic compounds and sunlight to potential hydrocarbon fuels and feedstocks for the chemical industry. Microorganisms such as B. braunii can, in the long run, reduce our dependence on fossil fuels and because of this B. braunii continues to attract much attention.     

Forest cover and fruit crop size differentially influence frugivory of select rainforest tree species in Western Ghats,India

Forest fragmentation and habitat loss are major disruptors of plant–frugivore interactions, affecting seed dispersal and altering recruitment patterns of the dependent tree species. In a heterogeneous production landscape (primarily tea and coffee plantations) in the southern Western Ghats, India, we examined effects of surrounding forest cover and fruit crop size on frugivory of four rainforest bird-dispersed tree species (N = 131 trees, ≥30 trees per species, observed for 623 hr). Frugivore composition differed among the four tree species with the large-seeded Canarium strictum and Myristica dactyloides being exclusively dependent on large-bodied avian frugivores, whereas medium-seeded Persea macrantha and Heynea trijuga were predominantly visited by small-bodied and large-bodied avian frugivores, respectively. Using the seed-dispersal-effectiveness framework, we identified effective frugivores and examined their responses to forest cover and fruit crop size. Results were idiosyncratic and were governed by plant and frugivore traits. Visitations to medium-seeded Persea had a positive relationship with forest cover but the relationship was negative for the large-seeded Myristica. In addition, two of the three effective frugivores for Persea responded to the interactive effect of forest cover and fruit crop size. Frugivore visitations to Heynea were not related to forest cover or fruit crop, and there were too few visitations to Canarium to discern any trends. These results highlight the context-specific responses of plant–frugivore interactions to forest cover and fruit crop size influenced by plant and frugivore traits.     

OCT layered tomography of the cornea provides new insights on remodeling after photorefractive keratectomy

OCT (optical coherence tomography) of corneal layers was generated to analyze the remodeling of the epithelium and stroma after photorefractive keratectomy (PRK). Myopic PRK was performed in 15 patients. One eye underwent manual scraping of epithelium while the other was treated with Epi clear. Epi clear allowed a gentler removal of the epithelium compared to manual scraping. Scheimpflug (Pentacam, OCULUS Optikgerate Gmbh, Wetzlar, Germany) and OCT (RTVue, Optovue Inc., Fremont, California, USA) scans of the cornea were performed before and after PRK (3 months). The OCT scanner and Pentacam acquired 8 and 25 radial 2‐D scans of the cornea, respectively. The results showed similar topographic changes on the anterior corneal surface between Scheimpflug and OCT imaging. The curvature of the underlying anterior surface of the stroma after PRK was similar to the anterior corneal surface (air‐epithelium interface), when measured with OCT. Aberrometric changes were mostly similar between Scheimpflug and OCT. However, Scheimpflug imaging reported greater changes in spherical aberration and corneal higher order aberrations than OCT after PRK. This is the first study to quantify the curvatures of the stromal layers with OCT after PRK. New insights were gained, which could be useful for refinement of surgical ablation algorithms, refractive procedures and detection of ectasia.      

Identification of potential inhibitors of Fasciola gigantica thioredoxin1: computational screening,molecular dynamics simulation,and binding free energy studies

Fasciola gigantica is the causative organism of fascioliasis and is responsible for major economic losses in livestock production globally. F. gigantica thioredoxin1 (FgTrx1) is an important redox-active enzyme involved in maintaining the redox homeostasis in the cell. To identify a potential anti-fasciolid compound, we conducted a structure-based virtual screening of natural compounds from the ZINC database (n = 1,67,740) against the FgTrx1 structure. The ligands were docked against FgTrx1 and 309 ligands were found to have better docking score. These compounds were evaluated for Lipinski and ADMET prediction, and 30 compounds were found to fit well for re-docking studies. After refinement by molecular docking and drug-likeness analysis, three potential inhibitors (ZINC15970091, ZINC9312362, and ZINC9312661) were identified. These three ligands were further subjected to molecular dynamics simulation (MDS) to compare the dynamics and stability of the protein structure after binding of the ligands. The binding free energy analyses were calculated to determine the intermolecular interactions. The results suggested that the two compounds had a binding free energy of –82.237, and –109.52 kJ.mol^?1 for compounds with IDs ZINC9312362 and ZINC9312661, respectively. These predicted compounds displayed considerable pharmacological and structural properties to be drug candidates. We concluded that these two compounds could be potential drug candidates to fight against F. gigantica parasites.