Specific deletion of CDC42 in pancreatic ß cells attenuates glucose-induced insulin expression and secretion in mice.

Insulin is a key hormone for maintaining glucose homeostasis in organisms. In general, deficiency of insulin synthesis and secretion results in type I diabetes, whereas insulin resistance leads to type 2 diabetes. Cell division cycle 42 (CDC42), a member of Rho GTPases family, has been shown as an essential regulator in the second phase of glucose-induced insulin secretion in pancreatic islets ß cells in vitro. However, the effect of CDC42 on insulin expression has not been explored. Here we reported that the glucose-induced insulin expression and secretion were significantly inhibited in mice lacking CDC42 gene in pancreatic ß cells (Rip-CDC42cKO) in vivo and in vitro. Deletion of CDC42 gene in pancreatic ß cells did not affect survival or reproduction in mice. However, the Rip-CDC42cKO mice showed the systemic glucose intolerance and the decrease of glucose-induced insulin secretion without apparent alterations of peripheral tissues insulin sensitivity and the morphology of islets. Furthermore, we demonstrated that deletion of CDC42 gene in pancreatic ß cells significantly attenuated the insulin expression through inhibiting the ERK1/2-NeuroD1 signaling pathway. Taken together, our study presents novel evidence that CDC42 is an important modulator in glucose-induced insulin expression as well as insulin secretion in pancreatic ß cells.

Recruitment of monocytes and epigenetic silencing of intratumoral CYP7B1 primarily contribute to the accumulation of 27-hydroxycholesterol in breast cancer.

Previous studies showed that intratumoral 27-Hydroxycholesterol (27-HC), a metabolite of cholesterol, promotes growth, invasion and migration of breast cancer cells and that tumor-associated macrophages (TAMs) in breast cancers are closely related to tumor growth and metastatic progression. However, the relationship between 27-HC and TAMs in breast cancer remains unclear. In the present study, we observed that CYP27A1, the 27-HC synthesizing enzyme, was expressed in a much higher level in THP1 monocytes and THP1-derived macrophages than in breast cancer cells, and the promoter of CYP7B1, the degrading enzyme for 27-HC, was highly methylated in breast tumor cells. In addition, THP-1 monocytes and murine bone marrow cells were differentiated toward M2 type macrophages after being co-cultured with breast cancer cells or being exposed to exosomes derived from breast cancer cells. M2 type macrophages produced higher amounts of 27-HC than M0 and M1 type macrophages. 27-HC not only stimulated ER+ cancer cell proliferation as reported, but also promoted the recruitment of CCR2- and CCR5-expressing monocytes by inducing macrophages to express multiple chemokines including CCL2, CCL3 and CCL4. Taken together, our data demonstrate that the hypermethylation of CYP7B1 and recruitment of monocytes likely contribute to the accumulation of 27-Hydroxycholesterol in breast cancer and that the interaction of 27-HC with macrophages further promote the development of breast cancer.

Diagnostic value of lymph node metastasis by diffusion-weighted magnetic resonance imaging in cervical cancer.

INTRODUCTION: Diffusion.weighted imaging. (DWI) combined with its apparent diffusion coefficient. (ADC) value shows great significance in the differential diagnosis of human tumors. This meta.analysis is to determine whether ADC valued in DWI could contribute to the differential diagnosis of positive and negative lymph node. (LN) metastasis in cervical cancer. (CC) or not. MATERIALS AND METHODS: A series of types of computerized databases were used searching for eligible studies relied on a strict inclusion and exclusion criteria. Two investigators were involved in the process of selecting articles and extracting dataset. Standardized mean differences (SMD) for the assessment of ADC values in positive and negative LN metastasis in CC patients were calculated. RESULTS: Fifteen cohort studies composed of 687 cases diagnosed with cervical tumor were incorporated into the current meta-analysis. Statistical analysis showed that the ADC value in positive LN metastasis was significantly lower than that with negative LN metastasis [SMD = 1.02, 95% confidence interval (CI) =0.54~1.50, P < 0.001]. Stratified by country, a lower ADC value in tumor tissues with LN metastasis was detected in comparison to that of tumor tissues without LN metastasis among China (SMD = 1.28, 95# CI = 0.62~1.94, P < 0.001) and Korea subgroups (SMD = 1.09, 95% CI = 0.65~1.52, P < 0.001). CONCLUSION: The ADC values in CC tissues with LN metastasis were significantly lower than those without LN metastasis, suggesting that DWI appears to improve diagnostic performance and can be a useful adjunct imaging for identifying LN metastasis in CC patients.

Evaluation of left atrial function in physiological and pathological left ventricular myocardial hypertrophy by real-time tri-plane strain rate imaging.

BACKGROUND: We investigated the difference between left ventricular (LV) hypertrophy caused by primary hypertension and physiological LV hypertrophy in athletes as seen in left atrial (LA) function by real-time tri-plane strain rate imaging. HYPOTHESIS: A real-time tri-plane imaging technique using the same phase of the same cardiac circle was used to synchronously demonstrate the section of apical 4-chamber, 2-chamber, and apical left ventricle long axis. METHODS: We measured standard Doppler echocardiographic quantitative analysis and the strain rate peak values of each LA wall in the systolic phase, in the early stage of diastole, and in the advanced stage of diastole and made a comparison of these values. RESULTS: The alteration of configuration and function of the left atrium in hypertensive patients is an early sign of the myocardial damage caused by hypertension. Strain rate imaging could sensitively reflect LA function changes in the early stages of hypertension. While physiological, myocardial hypertrophy is a benign reaction, LA function is significantly different from that of hypertension. CONCLUSIONS: Real-time tri-plane strain rate imaging techniques could simultaneously analyze 3 sections, which shortens scanning time and depletes the influence of variations of different cardiac cycles on quantitative analysis of local myocardial segments of the left atrium. This would improve the comparability of myocardial movement of different segments so that we could more comprehensively and accurately evaluate the systolic and diastolic function of the left atrium in primary hypertension and physiological LV hypertrophy in athletes.