Diet changes due to urbanization in South Africa are linked to microbiome and metabolome signatures of Westernization and colorectal cancer.

Transition from traditional high-fiber to Western diets in urbanizing communities of Sub-Saharan Africa is associated with increased risk of non-communicable diseases (NCD), exemplified by colorectal cancer (CRC) risk. To investigate how urbanization gives rise to microbial patterns that may be amenable by dietary intervention, we analyzed diet intake, fecal 16 S bacteriome, virome, and metabolome in a cross-sectional study in healthy rural and urban Xhosa people (South Africa). Urban Xhosa individuals had higher intakes of energy (urban: 3,578 ± 455; rural: 2,185 ± 179 kcal/d), fat and animal protein. This was associated with lower fecal bacteriome diversity and a shift from genera favoring degradation of complex carbohydrates (e.g., Prevotella) to taxa previously shown to be associated with bile acid metabolism and CRC. Urban Xhosa individuals had higher fecal levels of deoxycholic acid, shown to be associated with higher CRC risk, but similar short-chain fatty acid concentrations compared with rural individuals. Fecal virome composition was associated with distinct gut bacterial communities across urbanization, characterized by different dominant host bacteria (urban: Bacteriodota; rural: unassigned taxa) and variable correlation with fecal metabolites and dietary nutrients. Food and skin microbiota samples showed compositional differences along the urbanization gradient. Rural-urban dietary transition in South Africa is linked to major changes in the gut microbiome and metabolome. Further studies are needed to prove cause and identify whether restoration of specific components of the traditional diet will arrest the accelerating rise in NCDs in Sub-Saharan Africa.

Design, synthesis, molecular modeling and anti-proliferative evaluation of novel quinoxaline derivatives as potential DNA intercalators and topoisomerase II inhibitors.

New series of [1,2,4]triazolo [4,3-a]quinoxaline and bis([1,2,4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives have been designed, synthesized and biologically evaluated for their cytotoxic activities against three tumor cell lines (HePG-2, Hep-2 and Caco-2). Compounds 16e, 21, 25a and 25b exhibited the highest activities against the examined cell lines with IC50 values ranging from 0.29 to 0.90 µM comparable to that of doxorubicin (IC50 ranging from 0.51 to 0.73 µM). The most active members were further evaluated for their topoisomerase II (Topo II) inhibitory activities and DNA intercalating affinities as potential mechanisms for their anti-proliferative activities. Interestingly, the results of Topo II inhibition and DNA binding assays were consistent with that of the cytotoxicity data, where the most potent anti-proliferative derivatives exhibited good Topo II inhibitory activities and DNA binding affinities, comparable to that of doxorubicin. Moreover, the most active compound 25a caused cell cycle arrest at G2/M phase and induced apoptosis in Caco-2 cells. In addition, Furthermore, molecular docking studies were performed for the novel compounds against DNA-Topo II complex to investigate their binding patterns. Based on these studies, it was concluded that DNA binding and/or Topo II inhibition may contribute to the observed cytotoxicity of the synthesized compounds.

Cyclin D1 expression in acute leukemia.

BACKGROUND: Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the involvement of cyclin D1 in acute leukemia. PATIENTS AND METHODS: In this study, we analyzed the expression of cyclin D1 at protein level in, 40 newly diagnosed patients with acute myeloid leukemia (AML), 10 patients with acute lymphoblastic leukemia (ALL), and 11 normal controls using flow cytometry. RESULTS: The expression of cyclin D1 was not significantly different in AML group as compared to normal controls. On the other hand, over expression of cyclin D1 was evident in ALL group (4/10) as compared to that in healthy control. The ALL cases with cyclin D1 over expression were significantly correlated to blast cell counts in the peripheral blood and bone marrow (BM) but not with hemoglobin level, WBC, and platelets count. The ALL group with lymphadenopathy and organomegaly express significantly higher cyclin D1 over expression as compared to those without. CONCLUSION: The biological value of cyclin D1 over expression might be different in AML and ALL.

Telomerase activity in bilharzial bladder cancer. Prognostic implications.

Background: Bladder cancer is a common malignancy in Egypt and other developing countries in which infection with Schistosoma haematobium is prevalent. Bladder cancer caused by bilharziasis has different clinical and biological characters than that observed in the western world. In this study, we used the TRAP technique to estimate telomerase activity in bilharzial bladder cancer specimens and we correlated the findings with other clinical and pathological findings. Patients and methods: Bladder cancer specimens were obtained from 57 patients who underwent radical cystectomy and pathological diagnosis was obtained in all patients. Tissue samples were frozen in liquid nitrogen and stored at -80 degrees C. Telomerase activity by PCR-ELISA technique was measured using TRAP technique. Results: Our patient group included 45 males and 12 females with a median age of 49 years. The majority of our patients (35/57) have squamous histology and they have proven bilharzial history shown in the pathology specimens. Stage P3b was encountered in 29/57 patients whereas thirty-five patients have grade II tumors. The majority of our patients (41/57) were negative for pelvic nodes metastases. Telomerase activity was detected in 27/57 patients (47.4%). The mean level of telomerase was 0.85+/-0.77 in positive patients and 0.029+/-0.025 in negative patients. The expression of telomerase and its mean level in patients above age of 60, in males and in those with squamous pathology, higher grade of tumors or positive node was higher than those without but the difference did not reach statistical significance (P>0.05). Alternatively, expression was significantly higher in those with stages (P1-P3a) compared with P3b-P4a disease stages (66.6% vs. 37.1, P=0.03). Conclusion: Telomerase activity is increased in bilharzial bladder cancer although to a lesser degree than that reported for TCC in the western world, which could be explained, by different biological behavior or different assay methods. Further larger studies with more number of patients are still needed to determine its potential value for early detection and possible use as a therapeutic target.