EVALUATION OF ANTIOXIDANT AND CHEMOPREVENTIVE POTENTIAL OF METHANOLIC EXTRACTS OF LEAF OF AEGLEMARMELOS ATTRIBUTES TOWARDS DUCTAL CARCINOMA STUDIED IN MCF7 CELLS

Objective: The objective of the present research work had been made to evaluate the antioxidant potential along with anti-cancer activity of methanolic extracts from the leaf of A. marmelos. Methods: Standard methods for antioxidant potential in terms of DPPH and nitric oxide scavenging assay, and anticancer activity in vitro method (Cytotoxicity/MTT assay and % of cell viability) by using MCF7 cell line. Results: Results of antioxidant efficacy revealed that the IC50 value for DPPH and nitric oxide scavenging assay was considered to be 62.032%, and 20.69% respectively. The methanolic extract of A. marmelos was found to possess enhanced anticancer potential against MCF7 cells. Cytotoxicity activity of MCF7 cells, when treated with methanolic extract of A. marmelos, was found to be 43.42% at 25µg, 52.31% at 50µg, 56.31% at 75µg, 58.38% at 100µg, 62.25% at 125µg. The IC50 value was found as 49.36µg. Toxicity was significantly increased with increased concentration and viability significantly decreased with the increased concentration of methanolic extract of leaf from A. marmelos for MCF7 cell when compared to cyclophosphamide. Conclusion: From the studies, it was postulated that methanolic extract of leaf from A. marmeloshas significant chemopreventive activity. These specific identities will be useful for the identification and authentication of raw drug

PREVALENCE AND FACTORS ASSOCIATED WITH OBESITY AMONG ADULT AT THE KAMPUNG KOLAM, EAST COAST MALAYSIAN PENINSULA-A CROSS SECTIONAL STUDY

Objective: This study assesses the prevalence of obesity and its associated factors among adults aged 18 y and above at the Kampaung kolam, Kuala Terengganu, Malaysia.Methods: This cross-sectional survey comprised of a semi-structured face to face interview questionnaire and collected anthropometric measurements and sex specific waist circumference in cm. The study population was 70 in total with 21 (30%) males and 49 (70%) females aged 18 y and above were selected by universal sampling. Body mass index (BMI) was used for weight status and sex specific waist circumference (WC) in cm was used for assessment of abdominal or central obesity at risk of metabolic complications associated with obesity.Results: Among men, the prevalence of underweight was 9.5%, normal weight 57.1%, overweight 14.3% and obesity 19.1%, while among women, the prevalence of underweight was 12.2%, normal weight 53.1%, overweight 14.3% and obesity 20.4%. Overall, 18 (25.7%) was obese and 52 (74.3%) was non-obese while sex specific WC in cm 19 (27.1%) was abdominal obese who were at risk of metabolic complication associated with obesity and 51 (72.9%) was not at risk. In chi-square association tests revealed that among respondents, currently married, unemployed and having family history with obesity were associated with generalized obesity while respondents who were currently married and having fast food frequently were associated with abdominal obesity and respondents who being currently married, unemployed and having fast food frequently were more likely to obese in generalized as well as abdominally.Conclusion: There was no association between generalized, abdominal and generalized and abdominal obesity with age, gender, education, flat floor structure, dietary patterns and habits, physical activities, sleep pattern and knowledge and attitude level towards obesity but those factors can be utilized in effective health promotion programmers of weight management strategies by targeting those factors in design for prevention of hypertension, diabetes and related cardio vascular diseases CVD

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It is great honor and privilege for me to be appointed as Member - Editorial Board, Universal Journal of Pharmaceutical Research (UJPR). My heartiest salutations to Prof. Dr. Kapil Kumar, Editor-in-Chief and the other board members for their accomplishment of today through their hard work and persistence. Indeed, UJPR is now recognized as an international rather than a domestic journal with a considerable proportion of manuscripts being contributed from outside the country. UJPR will continue to adhere to its original philosophy of promoting the sharing of basic medical science experience by our members.    I believe that the most critical components of any scientific journal's success are the submission of high-quality manuscripts, the dedication of members of its editorial board, and excellence of those reviewing the manuscripts. We will take utmost care for rigorous peer review of all submitted manuscripts to accept only quality contents without any fringe of conflict for publication. I will take this opportunity to appeal to all authors to prepare their manuscripts strictly according to journal instructions so as to avoid any undue delay in its editorial processing and disappointment of rejection.                                                                           Now we are in the epoch of Cross disciplinary research based publications within the (preclinical) boulevards which usually assimilates information, data, techniques, tools, perspectives, concepts and / or theories from two or more disciplines of focused knowledge to progress rudimentary understanding or to decipher glitches whose solutions are outside the scope of a single discipline or area of research practice. Interdisciplinarians publish the manuscripts by mixing the best elements of disciplinary insights by crossing their parent discipline in order to generate a more wide-ranging appreciation of the issue at hand. Interdisciplinary publication allows for the synthesis of ideas and the synthesis of characteristics from many fields. Hopefully, UJPR Chief with support from editorial ­team will strive to generate an impact factor for which we invite submission of more original articles and citation of relevant literature published in this journal in your future publications

PHYTOCHEMICAL SCREENING, ANTIOXIDANT POTENTIAL AND CYTOTOXIC ACTIVITY OF MELASTOMA MALABATHRICUM LINN. FROM DIFFERENT LOCATIONS

Objective: The initial study was to screen the phytochemical content of methanol extract of M. malabathricum from seven different locations. The other objective was to evaluate the total phenolic content (TPC), Total flavonoid content (TFC), antioxidant potential and cytotoxic activity (on Hepatoma G2 cells) of these extracts and to determine the relationship between TPC and other parameters.Methods: The preliminary phytochemical screening for the presence of the secondary metabolite was carried out according to standard procedures. TheTPC,TFC and antioxidant activity were determined using Folin-Ciocalteu method, aluminium chloride (colorimetric) methodand1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity respectively.Results: Qualitative phytochemical screening showed the presence of tannins, analkaloid, steroids, flavonoid, phenols, terpenoids and fixed oil but tested negative for the presence of glycoside and saponins. The samples were found to have high TPC and antioxidant activity. The Bachok Kelantan sample (L7) showed highest phenolic content (671.51±50.07 mg of GAE/g) as well as highest DPPH free radical scavenging activity (80.81% and IC50 102 µg/ml). The highest cytotoxic activity against HepG2 cells (IC50 1.4µg/ml) was shown by KualaTerengganu, Terengganu sample (L1). The Spearman correlation showed that, there is a strong positive correlation between TPC and antioxidant activity (r = 0.714) as well as strong negative correlation between MTT IC50 and TPC (R =-0.649) of M. malabathricum from different locations. Moreover, there is a weak positive correlation between TFC and antioxidant activity (R = 0.286, p= 0.535). Also, there is poor correlation between TFC and cytotoxicity (R =-0.216, p= 0.64).Conclusion: The phenolic compounds are associated with the cytotoxic and antioxidant activities of M. malabathricum, whereas flavonoids are poorly and weakly associated with cytotoxic and antioxidant activities of M. malabathricum respectively. The total phenolic content, mean flavonoid content and mean antioxidant activity of M. malabathricum from different locations were significantly different across seven locations (p<0.05).Â

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe

Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. METHODS: We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. RESULTS: Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05). Mean coefficient of variation within patients (CVi) for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p < 0.01). Mean CVi for fibrinogen fragments in plasma was 20.5% and for JM403 in urine was 27.8%. No correlations were found between fibrinogen fragments or JM403 epitope and desmosines. CONCLUSION: We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects

Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study

BACKGROUND: Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD). METHODS: We genotyped 9131 individuals from the adult Danish population for cystic fibrosis 5T, 7T, 9T, and F508del alleles, and examined associations between 11 different genotype combinations, and annual FEV(1 )decline and risk of asthma or COPD. RESULTS: 5T heterozygotes vs. 7T homozygous controls had no increase in annual FEV(1 )decline, self-reported asthma, spirometry-defined COPD, or incidence of hospitalization from asthma or COPD. In 5T/7T heterozygotes vs. 7T homozygous controls we had 90% power to detect an increase in FEV(1 )decline of 8 ml, an odds ratio for self-reported asthma and spirometry-defined COPD of 1.9 and 1.7, and a hazard ratio for asthma and COPD hospitalization of 1.8 and 1.6, respectively. Both 5T homozygotes identified in the study showed evidence of asthma, while none of four 5T/F508del compound heterozygotes had severe pulmonary disease. 7T/9T individuals had annual decline in FEV(1 )of 19 ml compared with 21 ml in 7T homozygous controls (t-test:P = 0.03). 6.7% of 7T homozygotes without an F508del allele in the cystic fibrosis transmembrane conductance regulator gene reported asthma vs. 11% of 7T/9T individuals with an F508del allele (χ(2):P = 0.01) and 40% of 7T homozygotes with an F508del allele (P = 0.04). 7T homozygotes with vs. without an F508del allele also had higher incidence of asthma hospitalization (log-rank:P = 0.003); unadjusted and adjusted equivalent hazard ratios for asthma hospitalization were 11 (95%CI:1.5–78) and 6.3 (0.84–47) in 7T homozygotes with vs. without an F508del allele. CONCLUSION: Polythymidine 5T heterozygosity is not associated with pulmonary dysfunction or disease in the adult Caucasian population. Furthermore, our results support that F508del heterozygosity is associated with increased asthma risk independently of the 5T allele

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action

Rearrangement processes and structural variations show evidence of selection in oesophageal adenocarcinomas

Oesophageal adenocarcinoma (OAC) provides an ideal case study to characterize large-scale rearrangements. Using whole genome short-read sequencing of 383 cases, for which 214 had matched whole transcriptomes, we observed structural variations (SV) with a predominance of deletions, tandem duplications and inter-chromosome junctions that could be identified as LINE-1 mobile element (ME) insertions. Complex clusters of rearrangements resembling breakage-fusion-bridge cycles or extrachromosomal circular DNA accounted for 22% of complex SVs affecting known oncogenes. Counting SV events affecting known driver genes substantially increased the recurrence rates of these drivers. After excluding fragile sites, we identified 51 candidate new drivers in genomic regions disrupted by SVs, including ETV5, KAT6B and CLTC. RUNX1 was the most recurrently altered gene (24%), with many deletions inactivating the RUNT domain but preserved the reading frame, suggesting an altered protein product. These findings underscore the importance of identification of SV events in OAC with implications for targeted therapies