Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer

Cancer was recently annexed to diabetic complications. Furthermore, recent studies suggest that cancer can increase the risk of diabetes. Consequently, diabetes and cancer share many risk factors, but the cellular and molecular pathways correlating diabetes and colon and rectal cancer (CRC) remain far from understood. In this study, we assess the effect of hyperglycemia on cancer cell aggressiveness in human colon epithelial adenocarcinoma cells in vitro and in an experimental animal model of CRC. Our results show that Nox (NADPH oxidase enzyme) 4-induced reactive oxygen species (ROS) production is deregulated in both diabetes and CRC. This is paralleled by inactivation of the AMPK and activation of the mammalian target of rapamycin (mTOR) C1 signaling pathways, resulting in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulation, induction of DNA damage, and exacerbation of cancer cell aggressiveness, thus contributing to the genomic instability and predisposition to increased tumorigenesis in the diabetic milieu. Pharmacologic activation of AMPK, inhibition of mTORC1, or blockade of Nox4 reduce ROS production, restore the homeostatic signaling of 8-oxoguanine DNA glycosylase/8-oxodG, and lessen the progression of CRC malignancy in a diabetic milieu. Taken together, our results identify the AMPK/mTORC1/Nox4 signaling axis as a molecular switch correlating diabetes and CRC. Modulating this pathway may be a strategic target of therapeutic potential aimed at reversing or slowing the progression of CRC in patients with or without diabetes.-Mroueh, F. M., Noureldein, M., Zeidan, Y. H., Boutary, S., Irani, S. A. M., Eid, S., Haddad, M., Barakat, R., Harb, F., Costantine, J., Kanj, R., Sauleau, E.-A., Ouhtit, A., Azar, S. T., Eid, A. H., Eid, A. A. Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer.Scopu

Characterization of the mineral trioxide aggregate-resin modified glass ionomer cement interface in different setting conditions

Introduction: Mineral trioxide aggregate (MTA) has been used successfully for perforation repair, vital pulpotomies, and direct pulp capping. However, little is known about the interactions between MTA and glass ionomer cement (GIC) in final restorations. In this study, 2 null hypotheses were tested: (1) GIC placement time does not affect the MTA-GIC structural interface and hardness and (2) moisture does not affect the MTA-GIC structural interface and hardness. Methods: Fifty cylinders were half filled with MTA and divided into 5 groups. The other half was filled with resin-modified GIC either immediately after MTA placement or after 1 or 7 days of temporization in the presence or absence of a wet cotton pellet. The specimens were then sectioned, carbon coated, and examined using a scanning electron microscope and an electron probe microanalyzer (SEM-EPMA) for interfacial adaptation, gap formation, and elemental analysis. The Vickers hardness numbers of the interfacial MTA were recorded 24 hours after GIC placement and 8 days after MTA placement and analyzed using the analysis of variance test. Results: Hardness testing 24 hours after GIC placement revealed a significant increase in hardness with an increase of temporization time but not with a change of moisture conditions (P <.05). Hardness testing 8 days after MTA placement indicated no significant differences among groups. SEM-EPMA showed interfacial adaptation to improve with temporization time and moisture. Observed changes were limited to the outermost layer of MTA. The 2 null hypotheses were not rejected. Conclusions: GIC can be applied over freshly mixed MTA with minimal effects on the MTA, which seemed to decrease with time

SARS-CoV-2 seroprevalence in the urban population of Qatar: An analysis of antibody testing on a sample of 112,941 individuals

ABSTRACTBackgroundQatar has experienced a large SARS-CoV-2 epidemic. Our first objective was to assess the proportion of the urban population that has been infected with SARS-CoV-2, by measuring the prevalence of detectable antibodies. Our second objective was to identify predictors for infection and for having higher antibody titers.MethodsResidual blood specimens from individuals receiving routine and other clinical care between May 12-September 9, 2020 were tested for anti-SARS-CoV-2 antibodies. Associations with seropositivity and higher antibody titers were identified through regression analyses. Probability weights were applied in deriving the epidemiological measures.ResultsWe tested 112,941 individuals (∼10% of Qatar’s urban population), of whom 51.6% were men and 66.0% were 20-49 years of age. Seropositivity was 13.3% (95% CI: 13.1-13.6%) and was significantly associated with sex, age, nationality, clinical-care type, and testing date. The proportion with higher antibody titers varied by age, nationality, clinical-care type, and testing date. There was a strong correlation between higher antibody titers and seroprevalence in each nationality, with a Pearson correlation coefficient of 0.85 (95% CI: 0.47-0.96), suggesting that higher antibody titers may indicate repeated exposure to the virus. The percentage of antibody-positive persons with prior PCR-confirmed diagnosis was 47.1% (95% CI: 46.1-48.2%), severity rate was 3.9% (95% CI: 3.7-4.2%), criticality rate was 1.3% (95% CI: 1.1-1.4%), and fatality rate was 0.3% (95% CI: 0.2-0.3%).ConclusionsFewer than two in every 10 individuals in Qatar’s urban population had detectable antibodies against SARS-CoV-2 between May 12-September 9, 2020, suggesting that this population is still far from the herd immunity threshold and at risk from a subsequent epidemic wave.</jats:sec

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

Efficacy, safety, and predictors of response to infliximab therapy for ulcerative colitis

Background Using infliximab (IFX), an antitumor necrosis factors antibody, has dramatically increased therapeutic choices for ulcerative colitis (UC). This study assessed IFX therapy’s efficacy, safety, and action predictor variables for UC. Patients and methods This prospective interventional study was done on 50 patients with UC. Patients underwent colonoscopy, biopsy, complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) before start of IFX and after 8 weeks. Patients started 5 mg/kg IFX infusion at 0, 2, and 6 weeks and then every eight weeks. After 6 months, cases were subjected to colonoscopy, biopsy, CRP, complete blood count, and ESR to assess IFX therapy. Results After therapy, hemoglobin and inactive UC cases (90%) increased significantly and white blood cell, ESR, and CRP decreased significantly than before treatment, without significant difference in platelet count. IFX treatment was associated with improvement in 90% of cases. There was a significant relation between improvement and colonoscopy, histopathology finding, and CRP after treatment (P<0.001) as the majority of cases had inactive UC, UC chronic phase with mild inflammation, and negative CRP after therapy. There was a nonsignificant relation between improvement and disease extension and severity (mayo clinic score) after the period. Conclusions Active UC cases treated by IFX had a better mucosal healing and clinical responses, corrected of anemia and thrombocytopenia and normalized acute-phase reaction

EFFECT OF BIOFERTILIZER AND COMPOST ON NITRATE STATUS, YIELD AND QUALITY OF POTATO TUBER UNDER NEWLY RECLAIMED SANDY SOIL

This investigation was carried out during the two summer seasons of 2015 and2016 in sandy soil on potato culitvar "Sante" to study the effect of using 100%compost (15 t/fed.) and 50% compost + nitrogen fixing bacteria (Azotobacter, andPseudomonas alone or together) on potato yield and quality as compared to theconventional mineral fertilization (120-75-150 kg/fed. NPK + 5 toncompost/fed.(control)). No significant differences in tubers yield/fed. were detectedbetween mineral fertilization (control) and using 100% compost (15t/fed).However, control treatment significantly produced a high yield per feddan,more than using 50% compost + any biofertilizer treatment.Using composttreatment at 15 t/fed.execeed all biofertilizer treatments in marketable yield in bothseasons, but without significant differences as compared with mineral fertilization(control).No significant differences in tuber dray matter and content of starch intuber were found between using compost treatment at 15 ton/fed. and mineralfertilization treatment (control)in both seasons. Nevertheless, application of 50%compost+ 4 applications of Azotobacter and Pseudomonas had the highest tuberconcentrations of starch and nitrogen with significant differences as compared withthe mineral fertilization.Using50% compost + 4 applications of Azotobacter orPseudomonas or both (Azotobacter + Pseudomonas )and application of 100%compost caused producing potato tubers with the lowest concentration of nitratewith significant differences as compared with the mineral fertilization. Nosignificant differences were detected between mineral and organic fertilizersconcerning P and K concentrations in tubers