Impacts of exposure to low concentration of titanium dioxide nanoparticles on cell cycle control and DNA repair in normal, cancer and DNA repair deficient cells.

Nowadays, Titanium dioxide nanoparticles, TiO2 NPs, are produced in huge quantities due to their vast range of applications including paints, food coloring, sunscreens and cosmetics. Consequently, humans are exposed to TiO2 NPs on a daily basis. However, the toxicological profile of TiO2 NPs is not fully elucidated. As a result, this study is carried out to evaluate the genotoxic impact of TiO2 NPs on normal, cancer and DNA repair deficient cells. Since most of the studies evaluated the genotoxic impact of the TIO2 NPs have used the acute exposure scenario: High exposure concentrations and short exposure times, in the present study the genotoxic impact of the NPs would be evaluated using the prolonged exposure scenario: low exposure concentration for long exposure time. Cytotoxicity on a cancer cell line was evaluated using the MTT assay, genotoxicity on normal and cancer cell line was evaluated using immunofluorescent staining for anti-γ-H2AX and anti-total-53BP1, and the impact of the NPs on cell cycle regulation was evaluated using G2/M checkpoint assay on normal and cancer cell lines. In order to study the impact of NPs on DNA repair genotoxicity was evaluated using immunofluorescent staining for anti-γ-H2AX and anti-total-53BP1 on normal and DNA repair deficient cell lines. Finally, the maintenance of cell cycle G2/M checkpoint in absence of DNA repair genes was evaluated using the G2/M checkpoint assay on DNA repair deficient cell lines. In the present study, we have demonstrated that long exposures to TiO2 NPs does not induces cytotoxicity but it causes significant genotoxicity, particularly DNA double strand breaks. More precisely, we verified that NPs induces DNA DSBs at heterochromatin as well as euchromatin regions of the genome. Furthermore, we demonstrated that DNA DSBs repair, during G1 phase, at heterochromatin region is ATM dependent while DNA DSBs repair at Euchromatin regions is ATM independent, and DNA PKcs and Artemis dependent. On the other hand, it was seen that activation of G2/M cell cycle checkpoint after exposure to the NPs has DNA DSBs dependent-threshold. Also, it was shown that the release of the cell cycle checkpoint has DNA DSBs dependent-threshold. Lastly, we observed cell cycle checkpoint adaptation on prolonged exposure scenario. Taken together, we have demonstrated that prolonged exposure scenario does not affect cell viability but it causes DNA damage and cell cycle checkpoint adaptation leading to genetic instability

Impacts of prolonged exposure to low concentration of titanium dioxide nanoparticles on cell cycle control and DNA repair

Although the toxicological profile of titanium dioxide nanoparticles is not fully illuminated, large quantities of titanium dioxide nanoparticles (TiO2NPs) are now produced. In our study, we evaluated the cytotoxic and genotoxic impacts of titanium dioxide nanoparticles on different cell lines (normal, cancer and DNA repair-deficient cells). MTT assay was used to evaluate the cytotoxicity, γ-H2AX and 53BP1 assay was used to evaluate the genotoxicity and G2/M assay was used to study the impacts of titanium dioxide nanoparticles on cell cycle regulation. In this study normal and DNA repair-deficient cell lines were used to study the repair mechanism of titanium dioxide nanoparticles induced DNA damage. G2/M checkpoint maintenance was also evaluated. We demonstrate that prolonged exposure to low concentrations of titanium dioxide nanoparticles does not induce significant cytotoxicity but induces significant genotoxicity, particularly DNA double-strand breaks (DNA DSBs). Furthermore, this study demonstrated that DNA DSBs at heterochromatin region are ATM-dependent and DNA DSBs at euchromatin region are ATM-independent and DNA PKcs dependent. After exposure to titanium dioxide nanoparticles, we show that the activation of G2/M checkpoint is DNA DSBs dependent threshold as does checkpoint release. All in all, we showed that prolonged exposure to low concentrations of titanium dioxide nanoparticles does not affect cell viability but causes DNA damage and cell cycle checkpoint adaptation which may lead to genetic instability. DOI: http://dx.doi.org/10.5281/zenodo.748742

Impacts of Empagliflozin (EMPA) Treatment on Skeletal Muscle Microvasculature in Type 1 Diabetic Rats

In individuals with type 1 diabetes (T1D) and models of the disease, hyperglycemia is associated with microvascular complications, including reduced capillary ratio in skeletal muscle (SM). We investigated whether a blood glucose lowering drug, empagliflozin (EMPA), has any impact on the microvasculature in SM. T1D was induced in eight-week-old male rats using streptozotocin (65 mg/kg, n=21). Twenty-one rats were given daily insulin and 11 of 21 rats also consumed EMPA (30 mg/kg/day) for 14 days. Twelve healthy non-diabetic rats served as controls. Capillary content and angiogenic factors were assessed in three separate leg muscles. EMPA+insulin treated rats exhibited better glycemic control, but capillary to fibre ratio and VEGFa mRNA was not impacted by EMPA+insulin treatment in the tibialis anterior. PECAM mRNA and VEGFa protein expression was also not impacted by EMPA+insulin treatment. EMPA has no obvious impact on the vasculature of SM in type 1 diabetic rodents

Impacts of Empagliflozin (EMPA) Treatment on Skeletal Muscle Microvasculature in Type 1 Diabetic Rats

In individuals with type 1 diabetes (T1D) and models of the disease, hyperglycemia is associated with microvascular complications, including reduced capillary ratio in skeletal muscle (SM). We investigated whether a blood glucose lowering drug, empagliflozin (EMPA), has any impact on the microvasculature in SM. T1D was induced in eight-week-old male rats using streptozotocin (65 mg/kg, n=21). Twenty-one rats were given daily insulin and 11 of 21 rats also consumed EMPA (30 mg/kg/day) for 14 days. Twelve healthy non-diabetic rats served as controls. Capillary content and angiogenic factors were assessed in three separate leg muscles. EMPA+insulin treated rats exhibited better glycemic control, but capillary to fibre ratio and VEGFa mRNA was not impacted by EMPA+insulin treatment in the tibialis anterior. PECAM mRNA and VEGFa protein expression was also not impacted by EMPA+insulin treatment. EMPA has no obvious impact on the vasculature of SM in type 1 diabetic rodents

Electromagnetic and weak hyperon properties in the Skyrme model

We report on the result of some investigations concerning the radiative decays of decuplet baryons and the non-leptonic weak decays of the octet baryons in the context of topological chiral soliton models. Our results are compared with those of alternative baryon models. For the radiative decays we find that the predictions are similar to those of quark models. In the case of the non-leptonic weak decays, we find that although the predicted S-wave amplitudes are in rather good agreement with the observed values, the model is not able to reproduce the empirical P-wave amplitudes. Thus, in contrast to previous expectations, the Skyrme model does not seem to provide a solution to the long-standing 'S-wave/P-wave puzzle'.Comment: 7 pages, 1 fig. Cont. to the Proc. of the "School on Electromagnetic probes and the structure of hadrons and nuclei". Erice, Italy. September 17- 24, 1999 to be published in Progress in Particle and Nuclear Physic

Public perceptions and attitudes toward thalassaemia: Influencing factors in a multi-racial population

<p>Abstract</p> <p>Background</p> <p>Thalassaemia is a common public health problem in Malaysia and about 4.5 to 6% of the Malays and Chinese are carriers of this genetic disorder. The major forms of thalassaemia result in death <it>in utero </it>of affected foetuses (α-thalassaemia) or life-long blood transfusions for survival in β-thalassaemia. This study, the first nationwide population based survey of thalassaemia in Malaysia, aimed to determine differences in public awareness, perceptions and attitudes toward thalassaemia in the multi-racial population in Malaysia.</p> <p>Methods</p> <p>A cross-sectional computer-assisted telephone interview survey of a representative sample of multi-racial Malaysians aged 18 years and above was conducted between July and December 2009.</p> <p>Results</p> <p>Of a total of 3723 responding households, 2846 (76.4%) have heard of thalassaemia. Mean knowledge score was 11.85 (SD ± 4.03), out of a maximum of 21, with higher scores indicating better knowledge. Statistically significant differences (<it>P </it>< 0.05) in total knowledge score by age groups, education attainment, employment status, and average household income were observed. Although the majority expressed very positive attitudes toward screening for thalassaemia, only 13.6% of married participants interviewed have been screened for thalassaemia. The majority (63.4%) were unsupportive of selective termination of foetuses diagnosed with thalassaemia major.</p> <p>Conclusion</p> <p>Study shows that carrier and premarital screening programs for thalassaemia may be more effective and culturally acceptable in the reduction of pregnancies with thalassaemia major. The findings provide insights into culturally congruent educational interventions to reach out diverse socio-demographic and ethnic communities to increase knowledge and cultivate positive attitudes toward prevention of thalassaemia.</p

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Internalized Islamophobia: The Discursive Construction of “Islam” and “Observant Muslims” in the Egyptian Public Discourse

This dissertation examines the way “Islam” and “observant Muslims” are represented in the Egyptian public discourse from 30 June 2012—which marks the arrival of President Mohammad Morsi, the first democratically elected president in Egypt, to power—to 30 June 2018, which marks the end of President Abdel Fattah el-Sisi’s first four-year presidential term. Through a Critical Discourse Analysis (CDA), 24 different episodes of some of the most widely watched late-night TV shows, and 2 official speeches were examined for a better understanding of how the Islamic faith is portrayed in a country with a Muslim majority such as Egypt. Results indicated that since President Morsi’s ascent to power, postcolonial self-acclaimed secular “liberals” and the ruling class have constructed an Islamophobic rhetoric derived from the Western Orientalist discourse through four specific representational practices: 1) establishing “Islam” as inherently problematic, violent, static, and incompatible with modernity and democracy; 2) creating a link between terrorism and the Islamic faith by claiming that violence is a religious obligation that has an essential place in Islam; 3) representing the “war on terrorism” as part of a struggle that seeks to defend Egypt and its values against “Islam” and “observant Muslims”; and 4) creating an image of “Egyptian-ness” dominated by Western perceptions of modernity. This hegemonic narrative seeks not only to justify the military coup d’�tat of 3 July 2013, but also to exclude “Islam” and “observant Muslims” from Egyptian society by creating fear of the religion and attaching narrow and negative connotations to the words “Islam” and “observant Muslims” that are signifiers for an undeterminable and diverse array of notions in existing manifestations of societies and individuals