Comparing prophylactic effect of exercise and metformin on cognitive brain functions in rats with type 3 diabetes mellitus.

Introduction: Type 2 diabetes mellitus (DM) and Alzheimer's disease (AD) are two major medical conditions that constitute a significant financial burden on most healthcare systems. Due to AD sharing "insulin resistance" mechanistic features with DM, some scientists have proposed "type 3 DM" terminology for it. This study aims to compare the prophylactic effect of exercise and metformin on cognitive brain functions in rats with type 3 DM. Material and methods: Two groups of rats were included in the study: the control group (n = 15) and the streptozotocin-induced type 2 diabetic group (n = 45). The diabetic group was subdivided into three equal subgroups: a sedentary non-treated diabetic group, an exercised group, and a metformin-treated group. We estimated step-down avoidance task latency, serum glucose, insulin, free fatty acids (FFA), cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TG), brain Aß-42 and glucose, histological changes by toluidine blue, and immunohistochemistry for brain Aß-42 and tau-positive cells. Results: Serum glucose, FFA, TG, cholesterol, LDL, brain Aß-42, brain glucose, the number of hippocampal dark and degenerated cells, and brain Aß-42 and tau-positive cells, were all significantly lower. In contrast, serum insulin and HDL, the number of hippocampal granular cells, and latency of the step-down avoidance task were significantly higher in exercised and metformin-treated groups compared to the diabetic group. There were significantly higher values of serum insulin and brain/plasma glucose ratio and number of brain tau-positive cells in the metformin-treated group than in the exercised group. Conclusions: We can conclude that exercise can be as effective as metformin regarding prophylaxis against the deleterious effects of type 3 DM on cognitive brain functions.

The functions and molecular mechanisms of Tribbles homolog 3 (TRIB3) implicated in the pathophysiology of cancer.

Currently, cancer ranks as the second leading cause of death worldwide, and at the same time, the burden of cancer continues to increase. The underlying molecular pathways involved in the initiation and development of cancer are the subject of considerable research worldwide. Further understanding of these pathways may lead to new cancer treatments. Growing data suggest that Tribble's homolog 3 (TRIB3) is essential in oncogenesis in many types of cancer. The mammalian tribbles family's proteins regulate various cellular and physiological functions, such as the cell cycle, stress response, signal transduction, propagation, development, differentiation, immunity, inflammatory processes, and metabolism. To exert their activities, Tribbles proteins must alter key signaling pathways, including the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/AKT pathways. Recent evidence supports that TRIB3 dysregulation has been linked to various diseases, including tumor development and chemoresistance. It has been speculated that TRIB3 may either promote or inhibit the onset and development of cancer. However, it is still unclear how TRIB3 performs this dual function in cancer. In this review, we present and discuss the most recent data on the role of TRIB3 in cancer pathophysiology and chemoresistance. Furthermore, we describe in detail the molecular mechanism TRIB3 regulates in cancer.

Human papillomavirus, gene mutation and estrogen and progesterone receptors in breast cancer: a cross-sectional study.

INTRODUCTION: recent studies show a good relationship between breast cancer (BC) and human papillomaviruses (HPV) wich is responsible for about 18% of BC cases. This study aimed to assess the relationship between different genotypes of HPV and the expression of P53 and retinoblastoma (RB) genes and estrogen and progesterone receptors in BC among Sudanese women. METHODS: one hundred and fifty tissue blocks were obtained from females diagnosed with BC. Positive samples were used to determine genotypes with an applied biosystem (ABI 3730XL) genetic analyzer for sequencing and immunohistochemistry. RESULTS: 13/150 samples showed HPV DNA. High-risk HPV-16 was detected in 5 cases, high-risk-HPV-58 was found in four cases, and HPV-18 was detected in three cases. Low-risk-HPV-11 was detected in a single invasive lobular carcinoma (ILC) case. P53 and RB gene mutations were detected in 35 and 30 BC cases, respectively. P53 gene mutation was frequently identified in grade (III) BC while RB gene mutation was positive in grade (II). Grade (II) BC had a higher incidence of HPV-16 and 58. On the other hand, HPV-18 had a higher incidence in grade (III). Estrogen and progesterone receptors were expressed in 94 and 79 HPV cases among the study group, respectively. CONCLUSION: this study elucidates the associations between HPV genotypes and BC. A statistically significant association was observed among p53 and RB gene mutations and different BC histological types. On the other hand, there was a statistically insignificant association between HPV genotyping and different BC gradings, BC histological types, P53 and RB genes mutations, and estrogen and progesterone receptor expression. Also, there was a statistically insignificant association among estrogen and progesterone receptors expression and BC grading. RB gene mutation was significantly associated with different BC grades. On the other hand, there was a statistically insignificant association between progesterone receptor expression and BC.