GIV/Girdin is a central hub for profibrogenic signalling networks during liver fibrosis.

Progressive liver fibrosis is characterized by the deposition of collagen by activated hepatic stellate cells (HSCs). Activation of HSCs is a multiple receptor-driven process in which profibrotic signals are enhanced and antifibrotic pathways are suppressed. Here we report the discovery of a signalling platform comprising G protein subunit, Gαi and GIV, its guanine exchange factor (GEF), which serves as a central hub within the fibrogenic signalling network initiated by diverse classes of receptors. GIV is expressed in the liver after fibrogenic injury and is required for HSC activation. Once expressed, GIV enhances the profibrotic (PI3K-Akt-FoxO1 and TGFβ-SMAD) and inhibits the antifibrotic (cAMP-PKA-pCREB) pathways to skew the signalling network in favour of fibrosis, all via activation of Gαi. We also provide evidence that GIV may serve as a biomarker for progression of fibrosis after liver injury and a therapeutic target for arresting and/or reversing HSC activation during liver fibrosis

EFFECT OF BOILING AND MICROWAVE ASSISTED PROCESSING ON THE ANTIMICROBIAL EFFICACY OF VITAMIN–C IN EMBLICA OFFICINALIS

Objective: The present work aimed to expand the awareness of restoring vitamin-C in its active form on different heat exposures. The effect of microwave-assisted processing and boiling of the aqueous crude extract of citrus fruit Emblica officinalis (amla) has been correlated with its antimicrobial efficacy against E. coli. Methods: The aqueous crude extract of dried amla pulp exposed to microwave radiation(600W,5 min) and boiling (5 min) were titrimetrically estimated for vitamin-C content by DCPIP-(2,6, Dinitrophenol indophenol) method and compared the same with the untreated sample. These three samples were studied for their effect on the growth pattern of E. coli turbidimetrically. The antimicrobial susceptibility test by agar cup well diffusion method was further followed to measure the zone of inhibitions (ZOI) for these three test extracts against E. coli. Results: The total estimated vitamin-C content was 26.76 mg/100g, 25.35 mg/100g and 21.12 mg/100g in the untreated extract (UTE), microwaved extract (MWE) and boiled extract (BE) respectively. At a higher concentration (0.8 mg/ml), the UTE showed a greater ZOI of 20 mm and a comparable ZOI of 18 mm for the MWE against E. coli. In addition, a reduced ZOI of 10 mm was recorded in case of the BE. At a lowest concentration (0.05 mg/ml), the UTE inhibited the growth with a least ZOI of 7 mm, whereas no inhibition zones were detected for MWE and BE at this concentration. Conclusion: The present investigation demonstrated the effect of boiling and microwave-assisted processing on the content of bioactive vitamin-C and its antimicrobial activity. The DCPIP method calculated a more vitamin-C retention in the MWE than the BE. As the boiling method destroyed the vitamin more rapidly, a higher growth rate of E. coli was measured in the presence of BE than the UTE and MWE. In addition, the antimicrobial assay also showed a least inhibitory effect against E. coli in the presence of the BE. A moderate inhibitory effect for MWE was also detected. Thus the present investigation proved that the boiling process destroys vitamin-C present in a food sample to a higher extent than the microwave-assisted processing