Glutathione S-Transferase activity and total thiol status in chronic alcohol abusers before and 30 days after alcohol abstinence

Background: Glutathione S Transferase (GST) has been involved in detoxification process in the liver and its activity has been shown to be increased in alcohol abusers. In the current work we measured the GST activity, total thiol status, AST, ALT, and direct bilirubin in chronic alcohol abusers before and 30 days after alcohol abstinence and lifestyle modification. Methods: Serum and urine GST activity and total thiol status were determined using spectrophotometric methods and serum transaminases were determined using clinical chemistry analyzer. Results: We found,significant increase in serum and urine GST (p<0.001), AST (p<0.001), ALT (p<0.001), and decrease in total thiol status (p<0.001) in chronic alcohol abusers. GST activity significantly decreased (p<0.001) and total thiol status were improved significantly (p<0.001) 30 days after alcohol abstinence and lifestyle modification. Conclusion: This study provides preliminary data to suggest the role of GST as prognostic indicator of alcohol abstinence with possible trend towards an improvement in liver function

A Comparative Study Between Alcoholics of Koraga Community, Alcoholics of General Population and Healthy Controls for Antioxidant Markers and Liver Function Parameters

Objectives: It is well established that long-term alcohol consumption leads to liver cirrhosis and other related disorders. Sufficient work has been done on biochemical markers of liver damage and antioxidant status of chronic alcoholics in general population. In the current study chronic alcoholics from a community called Koraga are analysed for the same parameters in a view to assess the extent of liver damage as compared to healthy controls and other alcoholics. Methods: Serum and urine samples from Koraga alcoholics (n=28), general alcoholics (n=30) and healthy controls (n=31) were analysed for liver function parameters and antioxidant markers. Liver function parameters were determined by automated analyzer. Markers of antioxidant status were estimated spectrophotometrically. The data was analysed using SPSS version 16.0. Results: There was significant increase in serum AST, serum ALT, serum GST and urine GST in both general and Koraga alcoholics when compared to healthy controls (p<0.0001). Serum ALT, serum GST and urine GST activity was significantly higher in general alcoholics when compared to Koraga alcoholics (p<0.001). Serum and urine total thiol levels were significantly lower in general alcoholics when compared to healthy controls and Koraga alcoholics (p<0.0001). We have observed no difference in total thiols level between healthy controls and Koraga alcoholics, in fact, there was significant increase in urine total thiols level in Koraga alcoholics compared to healthy controls (p<0.001). On Pearson’s correlation serum AST, serum ALT correlated positively with serum and urine GST (p<0.0001) and negatively with serum total thiols (p<0.0001). Serum GST correlated negatively with serum total thiols (p<0.0001). Conclusion: Results of our study possibly indicate that the extent of alcohol induced liver damage in Koraga subjects is comparatively lower than general alcoholics, even though the alcohol consumption is found to be higher in them. There may be some mechanism that is rendering them resistant to alcoholic liver damage which needs to be explored through further studies at molecular level

Anti-proliferative activity of silver nanoparticles

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Differential regulation of intracellular factors mediating cell cycle, DNA repair and inflammation following exposure to silver nanoparticles in human cells

10.1186/2041-9414-3-2Genome Integrity3

A study on sporadic renal cell carcinoma in young adults, our institutional experience

Background: Renal cell carcinoma (RCC) accounts for around 2–3% of all adult malignant neoplasms. Most RCC instances are sporadic, with about 4–6% being familial. Sporadic RCC is uncommon in young patients under 45, accounting for 3–7% of all instances. We report our experience with sporadic RCCs in young adults between the age of 20 and 45 years. Aims and Objectives: The aim is to study clinical presentation, evaluation, management, and prognosis of sporadic RCC in young adults. Materials and Methods: A retrospective review of 22 patients diagnosed with sporadic RCC between ages 20 and 45 years during a period of 7 years from 2016 to 2022 was performed at Government Stanley Medical College. Demographic details such as age, gender, clinical condition, blood investigations, radiological imaging, and histopathological evaluation were conducted. Patients were assessed for long-term outcomes by comparing metastasis and lymph node involvement with survival outcomes. Results: The mean age at diagnosis was 37 years. Most patients belong to lower socioeconomic status (54.5%), Tumors were detected incidentally in 9 patients (41%) and were symptomatic in 13 (59%). Around 87% of patients were not having any associated comorbidities. The average duration of presenting complaints in symptomatic patients was 41 days. About 59% of patients were smokers or chewing tobacco before diagnosis. Renal biopsy was performed in 27% of patients before definitive surgery. The difference in prognosis was found to be insignificant between patients who were asymptomatic at the time of diagnosis compared to patients who were symptomatic. The tumor stage and grade had a significant impact on survival. The mean postoperative follow-up was 38 months. Conclusion: The result of our study shows that sporadic RCC does not behave aggressively in young adults. The most important determinants in prognosis are tumor stage and histological grade. The type of surgical procedure does not affect the overall outcome

Comparative proteomic analysis of spermatozoa isolated by swim-up or density gradient centrifugation

Abstract BACKGROUND: Reports about the morphologic and functional characteristics of spermatozoa prepared by density gradient centrifugation (DC) or swim-up (SU) have produced discordant results. We have performed a proteomic comparison of cells prepared by DC and SU providing a molecular insight into the differences between these two methods of sperm cell isolation. METHODS: Protein maps were obtained by 2-dimensional (2-D) separations consisting of isoelectrofocusing (IEF) from pI 3 to 11 followed by SDS-polyacrylamide gel electrophoresis. 2-D gels were stained with Sypro Ruby. Map images of DC and SU spermatozoa were compared using dedicated software. Intensities of a given spot were considered different between DC and SU when their group mean differed by >1.5-fold (p<0.05, Anova). RESULTS: No differences were observed for 853 spots, indicating a 98.7% similarity between DC and SU. Five spots were DC>SU and 1 was SU>DC. Proteins present in 3 of the differential spots could be identified. One DC>SU spot contained lactate dehydrogenase C and gamma-glutamylhydrolase, a second DC>SU spot contained fumarate hydratase and glyceraldehyde-3-phosphate dehydrogenase-2, and a SU>DC spot contained pyruvate kinase M1/M2. CONCLUSIONS: The differences in protein levels found on comparison of DC with SU spermatozoa indicate possible dissimilarities in their glycolytic metabolism and DNA methylation and suggest that DC cells may have a better capacitation potential

Honey health benefits and uses in medicine

The generation of reactive oxygen species (ROS) and other free radicals during metabolism is an essential and normal process that ideally is compensated through the antioxidant system. However, due to many environmental, lifestyle, and pathological situations, free radicals and oxidants can be produced in excess, resulting in oxidative damage of biomolecules (e.g., lipids, proteins, and DNA). This plays a major role in the development of chronic and degenerative illness such as cancer, autoimmune disorders, aging, cataract, rheumatoid arthritis, cardiovascular, and neurodegenerative diseases (Pham-Huy et al. 2008; Willcox et al. 2004). The human body has several mechanisms to counteract oxidative stress by producing antioxidants, which are either naturally synthetized in situ, or externally supplied through foods, and/or supplements (Pham-Huy et al. 2008).info:eu-repo/semantics/publishedVersio

Indian summer monsoon onset forecast skill in the UK Met Office initialized coupled seasonal forecasting system (GloSea5-GC2)

Accurate and precise forecasting of the Indian monsoon is important for the socio-economic security of India, with improvements in agriculture and associated sectors from prediction of the monsoon onset. In this study we establish the skill of the UK Met Office coupled initialized global seasonal forecasting system, GloSea5-GC2, in forecasting Indian monsoon onset. We build on previous work that has demonstrated the good skill of GloSea5 at forecasting interannual variations of the seasonal mean Indian monsoon using measures of large-scale circulation and local precipitation. We analyze the summer hindcasts from a set of three springtime start-dates in late April/early May for the 20-year hindcast period (1992-2011). The hindcast set features at least fifteen ensemble members for each year and is analyzed using five different objective monsoon indices. These indices are designed to examine large and local-scale measures of the monsoon circulation, hydrological changes, tropospheric temperature gradient, or rainfall for single value (area-averaged) or grid-point measures of the Indian monsoon onset. There is significant correlation between onset dates in the model and those found in reanalysis. Indices based on large-scale dynamic and thermodynamic indices are better at estimating monsoon onset in the model rather than local-scale dynamical and hydrological indices. This can be attributed to the model's better representation of large-scale dynamics compared to local-scale features. GloSea5 may not be able to predict the exact date of monsoon onset over India, but this study shows that the model has a good ability at predicting category-wise monsoon onset, using early, normal or late tercile categories. Using a grid-point local rainfall onset index, we note that the forecast skill is highest over parts of central India, the Gangetic plains, and parts of coastal India - all zones of extensive agriculture in India. El Niño Southern Oscillation (ENSO) forcing in the model improves the forecast skill of monsoon onset when using a large-scale circulation index, with late monsoon onset coinciding with El Niño conditions and early monsoon onset more common in La Niña years. The results of this study suggest that GloSea5's ensemble-mean forecast may be used for reliable Indian monsoon onset prediction a month in advance despite systematic model errors

Therapeutic opportunities within the DNA damage response

The DNA damage response (DDR) is essential for maintaining the genomic integrity of the cell, and its disruption is one of the hallmarks of cancer. Classically, defects in the DDR have been exploited therapeutically in the treatment of cancer with radiation therapies or genotoxic chemotherapies. More recently, protein components of the DDR systems have been identified as promising avenues for targeted cancer therapeutics. Here, we present an in-depth analysis of the function, role in cancer and therapeutic potential of 450 expert-curated human DDR genes. We discuss the DDR drugs that have been approved by the US Food and Drug Administration (FDA) or that are under clinical investigation. We examine large-scale genomic and expression data for 15 cancers to identify deregulated components of the DDR, and we apply systematic computational analysis to identify DDR proteins that are amenable to modulation by small molecules, highlighting potential novel therapeutic targets

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figuresMajor update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figuresThe preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess