Mitochondrial fumarate promotes ischemia/reperfusion-induced tubular injury.

AIM: Mitochondrial dysfunction, a characteristic pathological feature of renal Ischemic/reperfusion injury (I/RI), predisposes tubular epithelial cells to maintain an inflammatory microenvironment, however, the exact mechanisms through which mitochondrial dysfunction modulates the induction of tubular injury remains incompletely understood. METHODS: ESI-QTRAP-MS/MS approach was used to characterize the targeted metabolic profiling of kidney with I/RI. Tubule injury, mitochondrial dysfunction, and fumarate level were evaluated using qPCR, transmission electron microscopy, ELISA, and immunohistochemistry. RESULTS: We demonstrated that tubule injury occurred at the phase of reperfusion in murine model of I/RI. Meanwhile, enhanced glycolysis and mitochondrial dysfunction were found to be associated with tubule injury. Further, we found that tubular fumarate, which resulted from fumarate hydratase deficiency and released from dysfunctional mitochondria, promoted tubular injury. Mechanistically, fumarate induced tubular injury by causing disturbance of glutathione (GSH) hemostasis. Suppression of GSH with buthionine sulphoximine administration could deteriorate the fumarate inhibition-mediated tubule injury recovery. Reactive oxygen species/NF-κB signaling activation played a vital role in fumarate-mediated tubule injury. CONCLUSION: Our studies demonstrated that the mitochondrial-derived fumarate promotes tubular epithelial cell injury in renal I/RI. Blockade of fumarate-mediated ROS/NF-κB signaling activation may serve as a novel therapeutic approach to ameliorate hypoxic tubule injury.

[Negative symptoms predict the improvement of social functioning of patients with schizophrenia].

OBJECTIVE: To identify predictive factors associated with the improvement of social functioning of schizophrenia patients in a community. METHODS: 101 schizophrenia patients undergoing community rehabilitation were assessed with the Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance Scale (PSP), Self-Esteem Scale (SES), Family Function Questionnaire (APGAR), and the World Health Organization Disability Assessment Scale II (WHODAS-II) twice 6 months apart. Pearson correlation and hierarchical multiple linear regression analyses were performed to identify the influencing and predictive factors associated with the improvement of social functioning. RESULTS: The increase of PSP score was correlated with age (r = 0.220), reduced PANSS negative score (r = 0.468), reduced PANSS general score (r = 0.392), reduced PANSS total score (r = 0.472), and reduced WHODAS-II Score (r = 0.247). The predictive factors of the change of PSP score followed the following order: change of PANSS negative score [the change of coefficient of determination (deltaR2 ) = 0.197], age of onset (deltaR2 = 0.048), change of WHODAS-II score and psychiatric rehabilitation (deltaR2 = 0.031). CONCLUSION: Improvement of negative symptoms predicts the short-term improvement of social functioning of schizophrenia patients.

Angiotensin II promotes the progression of human gastric cancer.

The renin-angiotensin system (RAS) plays an important role in cardiovascular homeostasis, carcinogenesis­related angiogenesis and cell proliferation. The present study was undertaken to determine the expression of angiotensin (Ang) II, Ang II type 1 and 2 receptors (AT1R and AT2R), and the activity of the angiotensin­converting enzyme (ACE) in gastric cancer tissue. The study further examined the roles of Ang II in the growth of gastric cancer cells in nude mice and in the migration and proliferation of MKN45 human gastric cancer cells. Gastric cancer tissue samples were obtained from gastric cancer patients. The levels of Ang II, AT1R and AT2R, as well as ACE activity were increased in tissues from gastric cancer patients compared to healthy tissues. A gastric cancer model was established by intraperitoneally injecting MKN45 human gastric cancer cells in nude mice, intraperitoneally injecting Ang II and measuring the tumor size every two days. Ang II treatment caused an increase in the size and weight of the tumor mass in nude mice, whereas the AT1R antagonist losartan significantly inhibited the size and weight of the tumor. While Ang II enhanced the migratory and proliferative rate of MKN45 human gastric cancer cells, these were significantly reduced following treatment with losartan. These results indicate that RAS is activated in gastric cancer patients and Ang II promotes the progression of gastric cancer in nude mice, as well as the migration and proliferation of MKN45 human gastric cancer cells.

[Relationship between body mass index and volume ratio of brain gray matter in patients with first-episode schizophrenia].

OBJECTIVE: To analyze the relationship between psychotic symptoms and body mass index (BMI) and brain mass index in patients with first-episode schizophrenia. METHODS: We identified 97 patients with first-episode and drug-free schizophrenia and compared their BMI and scare MRI results with 97 healthy participants. RESULTS: There were no statistically significant differences in BMI, volume of white matter and volume of grey matter between the patients with schizophrenia and healthy participants. BMI was positively correlated with age and negatively correlated with gray matter volume and the ratio of gray matter volume in the healthy participants. No such correlations were found in the patients with schizophrenia. BMI were not correlated with the total score of PANSS, nor with the factor score of PANSS. CONCLUSION: BMI is positive correlated with age, but negatively correlated with gray matter volume and the ratio of gray matter volume in healthy adult. But such correlations disappear in patients with schizophrenia. BMI is not associated with the seriousness of psychotic symptoms.