Yes / The present study investigated the genoprotective and genotoxic effects of myricetin bulk (10 μM) and nano forms (20 μM) in the lymphocytes from pre-cancerous, monoclonal gammopathy of unknown significance (MGUS) patients and healthy individuals using the Comet and micronucleus assays. The study also evaluated the effect of myricetin on P53 expression levels, using the Western blot technique. Results showed that throughout the in-vitro treatment, lymphocytes from the patients group had higher levels of baseline DNA damage compared to the healthy group. Myricetin in both forms induced significant DNA damage, only at higher concentrations (>40 μM). The micronucleus assay showed a significant reduction (P < 0.01) in the frequency of micronuclei in mono-nucleated cells in the patient group treated with the nano form of myricetin at the non-toxic dose of 20 μM. There was a significant increase in both gene and protein P53 levels in lymphocytes isolated from healthy individuals and pre-cancerous patients. These results suggested a protective effect of myricetin and indicated its nutritional supplement potential for protection against cancer development among patients suffering from MGUS. / This study was kindly funded by Mr Nasir Qayyum, Bradford, UK.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. It has commonly been associated with exposure to tobacco-derived carcinogens and alcohol consumption. Pembrolizumab has shown to be effective in the treatment of many types of cancers such as melanoma, non-small cell lung cancer, due to its antiproliferative, immunoregulatory properties. The aim of this study was to investigate the effects of naked Pembrolizumab and Pembrolizumab liposome on the level of DNA damage, gene, and protein expressions in peripheral lymphocytes from HNC patients and compared to the healthy individuals by using the Comet and micronucleus assays. Western blotting and real-time polymerase chain reaction were performed to assess the potential of improving the repair mechanisms after treatment with naked Pembrolizumab and Pembrolizumab liposome. According to the results, Comet assay and micronucleus assay showed a significantly decreased DNA damage in the lymphocytes from HNC patients after being treated with naked Pembrolizumab and pembrolizumab liposome. Furthermore, the results have shown that naked Pembrolizumab and pembrolizumab liposomes (10 μg/ml) greatly decreased the oxidative stress produced by H2O2. Both forms of pembrolizumab have also demonstrated improving the repair mechanisms in lymphocytes from HNC patients by modulating the expression of P53, P21, and Bcl-2 at mRNA and protein levels. This study suggested that Pembrolizumab naked and liposome could have an antioxidant role alongside other actions in the treatment of HNSCC. However, further studies on Cancer cell lines and in vivo observation are required to validate the anticancer potential of pembrolizumab naked with liposome in HNC. / Ministry of Higher Education and Scientific Research, Libya

Lung cancer is one of the main causes of death worldwide, with most patients suffering from an advanced unresectable or metastatic non-small cell lung cancer. The mortality trends are mostly related to patterns of tobacco use, specifically from cigarettes. Tobacco is the basic etiological agent found as a consequence of the inhalation of tobacco smoke. Published data show the use of interferons (IFNs) in the treatment of lung tumours due to their potential in displaying antiproliferative, anti-angiogenic, immunoregulatory, and proapoptotic effects. Type1 IFNs have been employed as treatments for many types of cancer, both for haematological cancers and solid tumours. The IFN-γ (naked) functions as an anticancer agent against various forms of cancer. Hence, this study aimed to investigate the genoprotective and genotoxic effects of IFN-γ liposome (nano) on 42 blood samples from lung cancer patients, compared to the same sample size from healthy individuals. The effectiveness of IFN- γ liposome against oxidative stress was also evaluated in this study. A concentration of 100U/ml of IFN-γ liposome was used to treat the lymphocytes in: Comet and micronucleus assays, Comet repair, Western blotting and real-time polymerase chain reaction (qPCR) were based on a preliminary test for the optimal dose. The lymphocytes from lung cancer patients presented with higher DNA damage levels than those of healthy individuals. IFN-γ liposome was not found to induce any DNA damage in the lymphocytes. Also, it caused a significant reduction in DNA damage in the lymphocytes from lung cancer patients in; Comet, Comet repair and micronucleus assays. Furthermore, the 100U/ml of IFN-γ liposome significantly reduced the oxidative stress caused by H2O2 and appeared to be effective in both groups using the Comet and micronucleus assays. Results from; Comet, Comet repair and micronucleus assays were consistent. The data obtained indicated that IFN-γ in both forms (naked INF-γ and INF-γ nano-liposome) may potentially be effective for the treatment of lung cancer and showed the ability of IFN-γ liposome to reduce the DNA damage more than the naked form. The IFN-γ in both forms has also shown anti-cancer potential in the lymphocytes from lung cancer patients by regulating the expression of p53, p21, Bcl-2 at mRNA and protein levels by up-regulating the p53 and p21 to mediate cell cycle arrest and DNA repair in lung cancer patients. The findings of this study are consistent with the view that the naked IFN-γ and liposome could have a significant role in cancer treatment, including lung cancer. / Mutah University in Jordan

Submitted by Izabel Franco (izabel-franco@ufscar.br) on 2016-09-19T20:00:07Z No. of bitstreams: 1 DissPRS.pdf: 1555305 bytes, checksum: ec8ce9901e9f1d2473840499dd064224 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-20T14:04:41Z (GMT) No. of bitstreams: 1 DissPRS.pdf: 1555305 bytes, checksum: ec8ce9901e9f1d2473840499dd064224 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-20T14:04:47Z (GMT) No. of bitstreams: 1 DissPRS.pdf: 1555305 bytes, checksum: ec8ce9901e9f1d2473840499dd064224 (MD5) / Made available in DSpace on 2016-09-20T14:04:54Z (GMT). No. of bitstreams: 1 DissPRS.pdf: 1555305 bytes, checksum: ec8ce9901e9f1d2473840499dd064224 (MD5) Previous issue date: 2015-02-27 / Background and objective: Dysanapsis ratio (DR), peak oxygen uptake (VO₂ peak) and age are studied as determinants of expiratory flow limitation (EFL) during exercise. However, it is not yet known whether they can elucidate EFL in young and middle-aged healthy individuals of the same sex. The objective of this study was to investigate the interaction between determinants of LFE (VO₂ peak, DR and age) during different exercise intensities performed in cycle ergometer. Methods: Twenty Two men, 11 young men, and 11 middle-aged men performed the following tests: measurement of respiratory muscle strength, lung function test (DR), cardiopulmonary test (VO₂ peak), and two constant load tests to assess EFL at loads of 75% and 125% of gas exchange threshold (GET). The unpaired t test and the Mann-Whitney test were used to compare groups and two-way ANOVA was used to analyze the effect of age and exercise intensity on the variables of the constant load test (CLT). Stepwise multiple regression was used to analyze the interaction between VO₂ peak, DR, and age and EFL. The significance level was set at p<0.05. Results: Only the middle-aged group presented EFL at both exercise intensities; the groups were similar in relation to respiratory muscle strength, VO₂ peak, and DR; EFL was not associated with VO₂ peak or DR, but it was associated with age during high-intensity exercise (p<0.001). Conclusion: In the experimental conditions, age was the only factor that was related to the presence of EFL during exercise. / Contextualização e objetivo: Dysanapsis ratio (DR), consumo de oxigênio pico (VO₂ pico) e a idade são estudados como determinantes da limitação ao fluxo expiratório (LFE) durante o exercício. No entanto, ainda não foi avaliado se eles podem justificar a presença de LFE em homens saudáveis, jovens e de meia idade. O objetivo deste trabalho foi verificar a interação entre determinantes da LFE (VO₂ pico, DR e idade) durante diferentes intensidades de exercício físico realizado em cicloergômetro. Métodos: Vinte e dois homens, 11 jovens e 11 meia idade, realizaram às seguintes avaliações: medida da força muscular respiratória, prova de função pulmonar (para medida da DR), teste cardiopulmonar (para medida do VO₂ pico) e dois testes de carga constante (TECC) para avaliação da LFE nas cargas de 75% LAv e 125% LAv. Utilizou-se o teste t não pareado e o teste de Mann-Whitney para comparar os grupos e ANOVA two-way para a análise do efeito da idade e da intensidade de exercício, nas variáveis do TECC. A análise de interação entre o VO₂ pico, a DR e a idade com a LFE foi feita por regressão múltipla, modelo stepwise. O nível de significância foi p<0,05. Resultados: Apenas o grupo meia idade apresentou LFE em ambas as intensidades de exercício; os grupos estudados não apresentaram diferenças em relação à força muscular respiratória, ao VO₂ pico e a DR; a LFE não apresentou relação com o VO₂ pico e a DR, mas se relacionou com a idade, durante exercício de alta intensidade (p<0,001). Conclusão: Nas condições experimentais estudadas, a idade foi o único fator que se relacionou com a presença de LFE durante o exercício em cicloergômetro. .

yes / To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius (AoS) in chronic cerebrospinal venous insufficiency (CCSVI)-positive and -negative healthy individuals using cine phase contrast imaging. Materials and Methods Fifty-one healthy individuals (32 CCSVI-negative and 19 age-matched CCSVI-positive subjects) were examined using Doppler sonography (DS). Diagnosis of CCSVI was established if subjects fulfilled ≥2 venous hemodynamic criteria on DS. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and routine 3T MRI outcomes. Results CCSVI was associated with increased CSF pulsatility in the AoS. Net positive CSF flow was 32% greater in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.008). This was accompanied by a 28% increase in the mean aqueductal characteristic signal (ie, the AoS cross-sectional area over the cardiac cycle) in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.021). Conclusion CSF dynamics are altered in CCSVI-positive healthy individuals, as demonstrated by increased pulsatility. This is accompanied by enlargement of the AoS, suggesting that structural changes may be occurring in the brain parenchyma of CCSVI-positive healthy individuals

No / PURPOSE: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius (AoS) in chronic cerebrospinal venous insufficiency (CCSVI)-positive and -negative healthy individuals using cine phase contrast imaging. MATERIALS AND METHODS: Fifty-one healthy individuals (32 CCSVI-negative and 19 age-matched CCSVI-positive subjects) were examined using Doppler sonography (DS). Diagnosis of CCSVI was established if subjects fulfilled >/=2 venous hemodynamic criteria on DS. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and routine 3T MRI outcomes. RESULTS: CCSVI was associated with increased CSF pulsatility in the AoS. Net positive CSF flow was 32% greater in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.008). This was accompanied by a 28% increase in the mean aqueductal characteristic signal (ie, the AoS cross-sectional area over the cardiac cycle) in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.021). CONCLUSION: CSF dynamics are altered in CCSVI-positive healthy individuals, as demonstrated by increased pulsatility. This is accompanied by enlargement of the AoS, suggesting that structural changes may be occurring in the brain parenchyma of CCSVI-positive healthy individuals.

No description available.