PurposeMany anticancer drugs induce apoptosis in malignant cells, and resistance to apoptosis could lead to suboptimal or no therapeutic benefit. Two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, act as a promoter and an inhibitor of apoptosis, respectively. Both Bax and Bcl-2 as well as their ratio have been regarded as prognostic markers in various cancers. However, conflicting results have been reported. A clear understanding of apoptosis has also become crucial due to reports about anti-Bcl-2 chemotherapy. We explored the relationship of Bax and Bcl-2 gene expression and their ratio with the therapeutic response in acute myeloid leukemia (AML) patients.Patients and methodsBone marrow and/or blood samples from 90 AML patients treated with cytarabine and daunorubicin were included. Expression of Bax and Bcl-2 was determined through real-time polymerase chain reaction by using ΔΔCt method of relative expression.ResultsBax and Bcl-2 expression among marrow and blood samples correlated with each other (rs=0.5, p<0.01). Although bone marrow expression of Bax and Bcl-2 tended to remain higher among responders (median 1.01 and 0.29, respectively) as compared to non-responders (median 0.66 and 0.24, respectively), the difference failed to reach statistical significance (U=784.5 and 733; p=0.68 and 0.28, respectively). Conversely, Bax/Bcl-2 ratio was higher among poor responders (median 3.07 vs 1.78), though again failed to reach statistical significance (U=698.5, p=0.07).ConclusionExpression of Bax and Bcl-2 does not differ significantly among AML patients treated with cytarabine and daunorubicin in terms of remission, relapse, resistance, overall survival, and disease-free survival, thus questioning the utility of emerging anti-Bcl-2 therapy.
BackgroundContemporary literature suggests that medical education might adversely affect students’ mental health. Alfaisal University in Riyadh, Saudi Arabia is a developing institution; hence, there has been a concern regarding the mental well-being of the students.ObjectivesThis study was designed to assess the traits of depression, anxiety, and stress among students in relation to potential underlying reasons.MethodsAll 575 medical students across the 5 years of study participated by filling out the Depression, Anxiety, and Stress Scale-21 (DASS-21) questionnaire anonymously twice. Firstly, 2–3 weeks before a major examination (pre-examination), and secondly, during regular classes (post-examination). Correlation was sought regarding sex, year of scholarship, attendance of a premedical university preparatory program (UPP), housing, and smoking. Subjective comments from students were also obtained.ResultsA total of 76.8% and 74.9% of students participated in pre-and post-examination groups, respectively. The majority were the children of expatriate workers in Saudi Arabia, and included Arabs, South Asians, and North Americans. Prevalence of depression, anxiety, and stress was high (43%, 63%, and 41%, respectively) which reduced (to 30%, 47%, and 30%, respectively) to some extent after examinations. Saudis and those who had attended UPP had higher DASS-21 scores. Smoking and female sex predicted higher levels of “baseline” depression, anxiety, or stress. The students perceived the curriculum and schedule to be the primary causes of their high DASS-21 scores.ConclusionThe students had high “baseline” traits of depression, anxiety, and stress, and these were higher if an examination was near, especially among Saudis and those who had attended UPP. Smoking and female sex predicted higher levels of “baseline” depression, anxiety, or stress. Students suggested that study burden and a busy schedule were the major reasons for their high DASS-21 scores.
Consumption of flavonoid-rich nutraceuticals has been associated with a reduction in coronary events. The present study analyzed the effects of cocoa flavonols on myocardial injury following acute coronary ischemia-reperfusion (I/R). A commercially available cocoa extract was identified by chromatographic mass spectrometry. Nineteen different phenolic compounds were identified and 250 mg of flavan-3-ols (procyanidin) were isolated in 1 g of extract. Oral administration of cocoa extract in incremental doses from 5 mg/kg up to 25 mg/kg daily for 15 days in Sprague Dawley rats (n = 30) produced a corresponding increase of blood serum polyphenols and become constant after 15 mg/kg. Consequently, the selected dose (15 mg/kg) of cocoa extract was administered orally daily for 15 days in a treated group (n = 10) and an untreated group served as control (n = 10). Both groups underwent surgical occlusion of the left anterior descending coronary artery and reperfusion. Cocoa extract treatment significantly reversed membrane peroxidation, nitro-oxidative stress, and decreased inflammatory markers (IL-6 and NF-kB) caused by myocardial I/R injury and enhanced activation of both p-Akt and p-Erk1/2. Daily administration of cocoa extract in rats is protective against myocardial I/R injury and attenuate nitro-oxidative stress, inflammation, and mitigates myocardial apoptosis.
Background: Sub-optimal HDL is a prognostic marker of cardiovascular disease. South Asia has a high prevalence of sub-optimal HDL compared to other parts of the world. Intermittent fasting (IF) is a type of energy restriction which may improve serum HDL and other lipids thereby reducing the risk of cardiovascular diseases.Objective: The aim of the study was to evaluate the effect of IF on lipid profile and HDL-cholesterol in a sample of South Asian adults.Methods: A 6-week quasi-experimental (non-randomized) clinical trial was conducted on participants with low HDL (< 40 mg/dl for men and < 50 mg/dl for women). Participants of the control group were recommended not to change their diet. The intervention group was recommended to fast for ~12 h during day time, three times per week for 6 weeks. Pulse rate, blood pressure, body weight, waist circumference, serum lipid profile, and blood glucose levels were measured at baseline and after 6 weeks.Result: A total of 40 participants were enrolled in the study (N = 20 in each group), while 35 (20 control and 15 intervention) completed the trial and were included in data analysis of the study. Body measurements, including body weight, BMI and waist circumference, showed significant interaction effects (p's < 0.001), indicating that there were larger reductions in the IF group than in the control group. Significant interaction effects were also observed for total (p = 0.033), HDL (p = 0.0001), and LDL cholesterol (p = 0.010) with larger improvements in the IF group.Conclusion: This study suggests that intermittent fasting may protect cardiovascular health by improving the lipid profile and raising the sub-optimal HDL. Intermittent fasting may be adopted as a lifestyle intervention for the prevention, management and treatment of cardiovascular disorders.Clinical Trial Registration: NCT03805776, registered on January 16, 2019, https://clinicaltrials.gov/ct2/show/NCT03805776
There is conflicting evidence that MDR1, MRP2 and LRP expression is responsible for chemotherapy resistance. We conducted this study to explore their role in AML therapy outcomes. Bone marrow and peripheral blood samples of 90 AML patients, receiving chemotherapy, were analyzed by real time PCR. Gene expression was calculated by the 2−ΔΔCt method. The patients who had a persistent remission were labelled ‘Good Responder’ (GRes) whereas, those with relapse or drug resistance were labelled ‘Poor Responders’ (PRes). Higher LRP expression in bone marrow, but not in peripheral blood, was positively associated with persistent remission (p = 0.001), GRes (p = 0.002), 1-year overall as well as disease-free survival (p = 0.02 and p = 0.007, respectively). Marrow and blood MDR1 and MRP2 expression did not differ significantly between the above groups. Logistic regression analysis showed that only a diagnosis of acute promyelocytic leukemia (APL; M3) or high marrow LRP expression significantly predicted a favorable therapeutic outcome. This is the first report showing that high bone marrow LRP expression predicts significant favorable therapeutic outcome. Peripheral blood LRP expression as well as marrow and blood MDR1 and MRP2 expression have no predictive value in AML patients treated with standard dose cytarabine and daunorubicin 3+7 regimen.
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