BackgroundIn the past year Lebanon has been experiencing a nutritional transition in food choices from the typical Mediterranean diet to the fast food pattern. As a consequence, the dietary habits of young adults have been affected; thus, overweight and obesity are increasingly being observed among the young. The purpose of this study is to assess the prevalence of overweight and obesity on a sample of students from the Lebanese American University (in Beirut) and to examine their eating habits.MethodsA cross-sectional survey of 220 students (43.6% male and 56.4% female), aged 20 ± 1.9 years, were chosen randomly from the Lebanese American University (LAU) campus during the fall 2006 semester. Students were asked to fill out a self-reported questionnaire that included questions on their eating, drinking and smoking habits. Also, their weight, height, percentage body fat and body mass index were measured. Body mass index (BMI) was used to assess students' weight status. Statistical analyses were performed using the Statistical Package for Social Sciences software (version 13.0) to determine overweight and obesity among students and to categorize eating habits.ResultsThis study showed that the majority of the students (64.7%) were of normal weight (49% male students compared to 76.8% female students). The prevalence of overweight and obesity was more common among male students compared to females (37.5% and 12.5% vs. 13.6% and 3.2%, respectively). In contrast, 6.4% female students were underweight as compared to 1% males. Eating habits of the students showed that the majority (61.4%) reported taking meals regularly. Female students showed healthier eating habits compared to male students in terms of daily breakfast intake and meal frequency. 53.3% of female students reported eating breakfast daily or three to four times per week compared to 52.1% of male students. There was a significant gender difference in the frequency of meal intake (P = 0.001). Intake of colored vegetables and fruits was common among students. A total of 30.5% reported daily intake of colored vegetables with no gender differences (31.5% females vs. 29.2% males). Alcohol intake and smoking were not common among students.ConclusionIn spite of the overall low prevalence of overweight and obesity in the studied sample, results indicate that university students would possibly benefit from a nutrition and health promotion program to reduce the tendency of overweight and obesity, especially among male students, and to im...
Topotecan, a topoisomerase I inhibitor, is an anticancer drug widely used in the therapy of lung, ovarian, colorectal, and breast adenocarcinoma. Due to the primary dose-limiting toxicity of topotecan, which is myelosuppressive, it is necessary to identify other chemotherapeutic agents that can work synergistically with topotecan to increase its efficacy and limit its toxicity. Many studies have shown synergism upon the combination of topotecan with other chemotherapeutic agents such as gemcitabine. Other studies have demonstrated that pre-exposing cells to naturally occurring compounds such as thymoquinone, followed by gemcitabine or oxaliplatin, resulted in higher growth inhibition compared to treatment with gemcitabine or oxaliplatin alone. Our aim was to elucidate the underlying mechanism of action of topotecan in the survival and apoptotic pathways in human colon cancer cell lines in comparison to thymoquinone, to study the proapoptotic and antiproliferative effects of thymoquinone on the effectiveness of the chemotherapeutic agent topotecan, and to investigate the potential synergistic effect of thymoquinone with topotecan. Cells were incubated with different topotecan and thymoquinone concentrations for 24 and 48 hours in order to determine the IC50 for each drug. Combined therapy was then tested with ± 2 values for the IC50 of each drug. The reduction in proliferation was significantly dose- and time-dependent. After determining the best combination (40 µM thymoquinone and 0.6 µM topotecan), cell proteins were extracted after treatment, and the expression levels of B-cell lymphoma 2 and of its associated X protein, proteins p53 and p21, and caspase-9, caspase-3, and caspase-8 were studied by Western blot. In addition, cell cycle analysis and annexin/propidium iodide staining were performed. Both drugs induced apoptosis through a p53-independent mechanism, whereas the expression of p21 was only seen in thymoquinone treatment. Cell cycle arrest in the S phase was detected with each compound separately, while combined treatment only increased the production of fragmented DNA. Both compounds induced apoptosis through the extrinsic pathway after 24 hours; however, after 48 hours, the intrinsic pathway was activated by topotecan treatment only. In conclusion, thymoquinone increased the effectiveness of the chemotherapeutic reagent topotecan by inhibiting proliferation and lowering toxicity through p53- and Bax/Bcl2-independent mechanisms.
Prostate cancer (PCa) is one of the most common cancer types in men worldwide. Heat shock proteins (HSPs) are molecular chaperones that are widely implicated in the pathogenesis, diagnosis, prognosis, and treatment of many cancers. The role of HSPs in PCa is complex and their expression has been linked to the progression and aggressiveness of the tumor. Prominent chaperones, including HSP90 and HSP70, are involved in the folding and trafficking of critical cancer-related proteins. Other members of HSPs, including HSP27 and HSP60, have been considered as promising biomarkers, similar to prostate-specific membrane antigen (PSMA), for PCa screening in order to evaluate and monitor the progression or recurrence of the disease. Moreover, expression level of chaperones like clusterin has been shown to correlate directly with the prostate tumor grade. Hence, targeting HSPs in PCa has been suggested as a promising strategy for cancer therapy. In the current review, we discuss the functions as well as the role of HSPs in PCa progression and further evaluate the approach of inhibiting HSPs as a cancer treatment strategy.
Niemann-Pick Type C (NP-C) is an inherited neurovisceral lysosomal storage disease characterized by a defect in the trafficking of endocytosed cholesterol. In 95% of patients the gene encoding NPC1 is affected. The correlation of the genetic background in NP-C with the clinical phenotype such as, severity and onset of liver dysfunction, ataxia, dystonia and vertical gaze palsy, has not been elucidated at the molecular level. We have designed strategies to investigate the effect of different mutations in the NPC1 gene at the protein and cellular levels. The NPC1 mutants were expressed in mammalian cells and their structural features, maturation pathways and subcellular localization elucidated. Interestingly, three classes of NPC1 mutants could be identified and further characterized. The first group comprised mutants in which the NPC1 protein revealed virtually similar structural features to the wild type species. It was trafficked to the lysosomes and colocalized with the lysosomal protein marker Lamp2. The second class of NPC1 mutants was only partially trafficked to the lysosomes, but predominantly localized to the endoplasmic reticulum (ER). In the third group with the most severe phenotype, NPC1 mutants were entirely retained in the ER, colocalizing with the ER-protein marker calnexin. In conclusion, this study relates NPC1 mutations to the trafficking behavior of the NPC1 mutants along the secretory pathway. The findings are essential for a comprehensive understanding of the pathogenesis of NP-C and propose a mutation-based personalized therapeutical approach.
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