Preliminary study of p53 and c-erbB-2 expression in gallbladder cancer in Indian patients manuscript id: 8962091628764582

BACKGROUND: The inactivation of the tumour suppressor gene and activation of the proto-oncogene are the key steps in the development of the human cancer. The p53 and c-erbB-2 are the best examples of it. In the present study, our aim was to determine the role of these genes in the carcinogenesis of gallbladder by immunohistochemistry. METHODS: In all 78 consecutive patients of gall bladder diseases were studied for p53 and c-erbB-2 expression immunohistochemically and their expression was correlated with the age, grades and stages of the disease and presence of stone. An informed consent was obtained in each case. Chi square and z test were applied to see the association of p53 and c-erbB-2 over expression with other clinicopathological factors. RESULTS: Eight (20%) patients of gall bladder cancer were positive for p53 expression and 10 (25%) patients for c-erbB-2. The p53 positivity increased with increasing grade while cerbB-2 positivity decreased with increasing grade of gall bladder cancer. Mean age in cerbB-2 positive cases were lesser as compared to negative cases while p53 did not show such association with age. CONCLUSION: Only one case of gall bladder cancer co-expressed the p53 and c-erbB-2, thereby suggesting that p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer. c-erbB-2 over expression in adenoma and younger age group indicates its role as an early event in carcinogenesis of gallbladder. However study of larger sample is required to further validate the results

Selection of the solvent and extraction conditions for maximum recovery of antioxidant phenolic compounds from coffee silverskin

The extraction of antioxidant phenolic compounds from coffee silverskin (CS) was studied. Firstly, the effect of different solvents (methanol, ethanol, acetone, and distilled water) on the production of antioxidant extracts was evaluated. All the extracts showed antioxidant activity (FRAP and DPPH assays), but those obtained with methanol and ethanol had significantly higher (p < 0.05) DPPH inhibition than the remaining ones. Due to the lower toxicity, ethanol was selected as extraction solvent, and further experiments were performed in order to define the solvent concentration, solvent/solid ratio, and time to maximize the extraction results. The best condition to produce an extract with high content of phenolic compounds (13 mg gallic acid equivalents/g CS) and antioxidant activity [DPPH = 18.24 μmol Trolox equivalents/g CS and FRAP = 0.83 mmol Fe(II)/g CS] was achieved when using 60 % ethanol in a ratio of 35 ml/g CS, during 30 min at 60–65 °C.This work was supported by the Portuguese Foundation for Science and Technology (FCT). The authors gratefully acknowledge Teresa Conde, student of Biological Engineering, for the help and interest in this work

Evaluation of alternative preservation treatments (water heat treatment, ultrasounds, thermosonication and UV-C radiation) to improve safety and quality of whole tomato

Previously optimised postharvest treatments were compared to conventional chlorinated water treatment in terms of their effects on the overall quality of tomato (‘Zinac’) during storage at 10 °C. The treatments in question were water heat treatment (WHT = 40 °C, 30 min), ultrasounds (US = 45 kHz, 80 %, 30 min), thermosonication (TS =40 °C, 30 min, 45 kHz, 80 %) and ultraviolet irradiation (UV-C: 0.97 kJ m−2). The quality factors evaluated were colour, texture, sensorial analysis, mass loss, antioxidant capacity, total phenolic content, peroxidase and pectin methylesterase enzymatic activities, and microbial load reduction. The results demonstrate that all treatments tested preserve tomato quality to some extent during storage at 10 °C. WHT, TS and UV-C proved to be more efficient on minimising colour and texture changes with the additional advantage of microbial load reduction, leading to a shelf life extension when compared to control trials. However, at the end of storage, with exception of WHT samples, the antioxidant activity and phenolic content of treated samples was lower than for control samples. Moreover, sensorial results were well correlated with instrumental colour experimental data. This study presents alternative postharvest technologies that improve tomato (Zinac) quality during shelf life period and minimise the negative impact of conventional chlorinated water on human safety, health and environment.info:eu-repo/semantics/publishedVersio

Active packaging of fish gelatin films with Morinda citrifolia oil

Active packaging is of interest in helping to prevent autoxidation process in foods. Morinda citrifolia contains a wide range of antioxidants such as ascorbic acid, terpenoids, and polyphenols. The purpose of this study was to determine the potential of Morinda citrifolia as a natural antioxidant in an active packaging film. Fish gelatin films incorporated with 1–3% of Morinda citrifolia oil (MO) were used to prepare antioxidant films. It was found that the incorporation of MO would not affect the thickness and solubility of gelatin films, independent of concentration. However, the solubility ranging from 13.4% to 13.8% might be considered low for these films. As for the mechanical properties, Young's modulus and elongation at break were not affected significantly by incorporation of 1–3% MO (p>0.05). As for the tensile strength, fish gelatin film incorporated with 1–3% MO showed a higher value than control (p≤0.05). The opacity between the samples and control varied statistically with the highest value with films containing 3% oil (p≤0.05). However, increasing the MO concentrations would decrease the water vapor permeability (p>0.05). DPPH (2,2-diphenyl-1-picrylhydrazyl) was used to determine the antioxidant activity and the result increased significantly (p≤0.05) from 9% to 16% with the increase of oil concentration, suggesting MO incorporation in films as potential means of active packaging

Active packaging of fish gelatin films with Morinda citrifolia oil

Active packaging is of interest in helping to prevent autoxidation process in foods. Morinda citrifolia contains a wide range of antioxidants such as ascorbic acid, terpenoids, and polyphenols. The purpose of this study was to determine the potential of Morinda citrifolia as a natural antioxidant in an active packaging film. Fish gelatin films incorporated with 1–3% of Morinda citrifolia oil (MO) were used to prepare antioxidant films. It was found that the incorporation of MO would not affect the thickness and solubility of gelatin films, independent of concentration. However, the solubility ranging from 13.4% to 13.8% might be considered low for these films. As for the mechanical properties, Young's modulus and elongation at break were not affected significantly by incorporation of 1–3% MO (p>0.05). As for the tensile strength, fish gelatin film incorporated with 1–3% MO showed a higher value than control (p≤0.05). The opacity between the samples and control varied statistically with the highest value with films containing 3% oil (p≤0.05). However, increasing the MO concentrations would decrease the water vapor permeability (p>0.05). DPPH (2,2-diphenyl-1-picrylhydrazyl) was used to determine the antioxidant activity and the result increased significantly (p≤0.05) from 9% to 16% with the increase of oil concentration, suggesting MO incorporation in films as potential means of active packaging

The Effect of DNA-Dependent Protein Kinase on Adeno-Associated Virus Replication

BACKGROUND: DNA-dependent protein kinase (DNA-PK) is a DNA repair enzyme and plays an important role in determining the molecular fate of the rAAV genome. However, the effect this cellular enzyme on rAAV DNA replication remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the roles of DNA-PK on recombinant adeno-associated virus DNA replication. Inhibition of DNA-PK by a DNA-PK inhibitor or siRNA targeting DNA-PKcs significantly decreased replication of AAV in MO59K and 293 cells. Southern blot analysis showed that replicated rAAV DNA formed head-to-head or tail-to-tail junctions. The head-to-tail junction was low or undetectable suggesting AAV-ITR self-priming is the major mechanism for rAAV DNA replication. In an in vitro replication assay, anti-Ku80 antibody strongly inhibited rAAV replication, while anti-Ku70 antibody moderately decreased rAAV replication. Similarly, when Ku heterodimer (Ku70/80) was depleted, less replicated rAAV DNA were detected. Finally, we showed that AAV-ITRs directly interacted with Ku proteins. CONCLUSION/SIGNIFICANCE: Collectively, our results showed that that DNA-PK enhances rAAV replication through the interaction of Ku proteins and AAV-ITRs

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC