Study to evaluate molecular mechanics behind synergistic chemo-preventive effects of curcumin and resveratrol during lung carcinogenesis.

BACKGROUND: The combination approach is the future of the war against cancer and the present study evaluated molecular mechanics behind the synergistic effects of curcumin and resveratrol during lung carcinogenesis. METHODS: The mice were segregated into five groups which included normal control, Benzo[a]pyrene[BP] treated, BP+curcumin treated, BP+resveratrol treated and BP+curcumin+resveratrol treated. RESULTS: The morphological analyses of tumor nodules confirmed lung carcinogenesis in mice after 22 weeks of single intra-peritoneal[i.p] injection of BP at a dose of 100 mg/Kg body weight. The BP treatment resulted in a significant increase in the protein expressions of p53 in the BP treated mice. Also, a significant increase in the protein expression of phosphorylated p53[ser15] confirmed p53 hyper-phosphorylation in BP treated mice. On the other hand, enzyme activities of caspase 3 and caspase 9 were noticed to be significantly decreased following BP treatment. Further, radiorespirometric studies showed a significant increase in the 14C-glucose turnover as well as 14C-glucose uptake in the lung slices of BP treated mice. Moreover, a significant rise in the cell proliferation was confirmed indirectly by enhanced uptake of 3H-thymidine in the lung slices of BP treated mice. Interestingly, combined treatment of curcumin and resveratrol to BP treated animals resulted in a significant decrease in p53 hyper-phosphorylation, 14C glucose uptakes/turnover and 3H-thymidine uptake in the BP treated mice. However, the enzyme activities of caspase 3 and caspase 9 showed a significant increase upon treatment with curcumin and resveratrol. CONCLUSION: The study, therefore, concludes that molecular mechanics behind chemo-preventive synergism involved modulation of p53 hyper-phosphorylation, regulation of caspases and cellular metabolism enzymes

Propensity of Withania somnifera to Attenuate Behavioural, Biochemical, and Histological Alterations in Experimental Model of Stroke

The present study was designed to evaluate the beneficial effects of Withania somnifera (WS) pre-supplementation on middle cerebral artery occlusion (MCAO) model of ischemic stroke. Ischemic stroke was induced in the rats by inserting intraluminal suture for 90 min, followed by reperfusion injury for 24 h. The animals were assessed for locomotor functions (by neurological deficit scores, narrow beam walk and rotarod test), cognitive and anxiety-like behavioural functions (by morris water maze and elevated plus maze test). MCAO animals showed significant impairment in locomotor and cognitive functions. Neurobehavioural changes were accompanied by decreased acetylcholinesterase activity, increased oxidative stress in terms of enhanced lipid peroxidation and lowered thiol levels in the MCAO animals. In addition, MCAO animals had cerebral infarcts and the presence of pycnotic nuclei. Single-photon emission computerized tomography (SPECT) of MCAO animals revealed a cerebral infarct as a hypoactive area. On the other hand, pre-supplementation with WS (300 mg/kg body weight) for 30 days to MCAO animals was effective in restoring the acetylcholinesterase activity, lipid peroxidation, thiols and attenuated MCAO induced behavioural deficits. WS significantly reduced the cerebral infarct volume and ameliorated histopathological alterations. Improved blood flow was observed in the SPECT images from the brain regions of ischemic rats pre-treated with WS. The results of the study showed a protective effect of WS supplementation in ischemic stroke and are suggestive of its potential application in stroke management

Effect of 22 weeks of curcumin and resveratrol treatments on the activity of alkaline phosphatase [ALP], lactate dehydrogenase[LDH] in serum of mice subjected to benzo[a]pyrene treatment.

<p>n = 10,Data are expressed in Mean ± S.D.</p>a<p>P≤0.05, ^bP≤0.01 and ^cP≤0.001 by Least Significance Difference test when values are compared with normal control group.</p>x<p>P≤0.05, ^zP≤0.001 by Least Significance Difference test when values of Groups III, IV & V are compared with Group II.</p>p<p>P≤0.05 by Least Significance Difference test when values of Groups V is compared with Group III.</p

Genome sequence and comparative genomic analysis of a clinically important strain CD11-4 of Janibacter melonis isolated from celiac disease patient

Abstract Background Janibacter melonis and other member of this genus are known to cause bacteremia and serious clinical comorbidities, but there is no study reporting about pathogenicity attributes of J. melonis. Janibacter terrae is known to cause lethal infection. Reporting the genome of J. melonis CD11-4 and comparative genomics with other members of genus has provided some novel insights that can enable us to understand the mechanisms responsible for its pathogenicity in humans. Results Comparative genomic analysis by Rapid Annotation Server and Technology revealed the presence of similar virulence determinant genes in both J. terrae NBRC 107853T and J. melonis CD11-4. Like J. terrae NBRC 107853T, J. melonis CD11-4 contained two genes responsible for resistance against β-lactam class of antibiotics and two genes for resistance against fluoroquinolones. Interestingly, J. melonis CD11-4 contained a unique gene coding for multidrug resistance efflux pumps unlike all other members of this genus. It also contained two genes involved in Toxin-antitoxin Systems that were absent in J. terrae NBRC 107853T but were present in some other members of genus. Conclusions Genome annotations of J. melonis CD11-4 revealed that it contained similar or more virulence repertoire like J. terrae NBRC 107853T. Like other gut pathogens, J. melonis possesses key virulence determinant genes for antibiotic resistance, invasion, adhesion, biofilm formation, iron acquisition and to cope with stress response, thereby indicating that strain J. melonis CD11-4 could be a gut pathogen

Effects of curcumin and resveratrol on protein expression of p53 by western blot analysis during lung carcinogenesis.

<p>Effects of curcumin and resveratrol on protein expression of p53 by western blot analysis during lung carcinogenesis.</p

Macroscopic view of lungs.

<p>[a] normal lung [b] Benzo[a]pyrene treated showing angeogenic lesions and marked inflammation [c] Benzo[a]pyrene treated lung showing tumors [close up] [d] Benzo[a]pyrene treated lung showing tumor, [e] Bezo[a]pyrene + Curcumin [f] Benzo[a]pyrene + Resveratrol [g] Benzo[a]pyrene +Curcumin + Resveratrol.</p

Effects of curcumin and resveratrol on protein expression of p53 by Immunhistochemistry [IHC at 10× magnification] during lung carcinogenesis.

<p>Effects of curcumin and resveratrol on protein expression of p53 by Immunhistochemistry [IHC at 10× magnification] during lung carcinogenesis.</p

Effects of curcumin and resveratrol on protein expression of phoshorylated p53[ser-15] by western blot analysis during lung carcinogenesis.

<p>Effects of curcumin and resveratrol on protein expression of phoshorylated p53[ser-15] by western blot analysis during lung carcinogenesis.</p

Effects of curcumin and resveratrol treatments on the <i>in vitro</i>³H-thymidine uptake in lungs during benzo[a]pyrene induced lung carcinogenesis.

<p>n = 10, Data are expressed in Mean ± S.D.</p>a<p>P<0.05, ^bP<0.01 and ^cP<0.001 by Least Significance Difference test when values are compared with normal control group.</p