MCU inhibition protects against intestinal ischemia‒reperfusion by inhibiting Drp1-dependent mitochondrial fission.

Intestinal ischemia‒reperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemia‒reperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified. In this study, we generated an IIR model using C57BL/6 mice and Caco-2 cells and found increases in the calcium levels and MCU expression following IIR injury. The specific inhibition of MCU markedly attenuated IIR injury. Moreover, MCU knockdown alleviates mitochondrial dysfunction by reducing oxidative stress and apoptosis. Mechanistically, MCU knockdown substantially reduced the translocation of Drp1 and thus its binding to Fis1 receptors, resulting in decreased mitochondrial fission. Taken together, our findings demonstrated that MCU is a novel upstream regulator of Drp1 in ischemia‒reperfusion and represents a predictive and therapeutic target for IIR.

[The correlation of synuclein-γ and matrix metalloproteinase 9 in breast cancer].

OBJECTIVES: To evaluate the expression of synuclein-γ (SNCG) and metalloproteinase 9 (MMP-9) both in the invasive ductal breast cancer samples and T47D and T47D(SNCG)- cell lines, to investigate the correlation between SNCG and MMP-9. METHODS: Totally 96 invasive ductal breast cancer samples (female, mean age of (56 ± 8) years) were collected between June 2009 and June 2012. The expressions of SNCG and MMP-9 were investigated by immunohistochemistry. T47D and SNCG knock down T47D(SNCG)- cell lines were established and SNCG and MMP-9 protein expression were investigated by Western blot and gene expression by real-time PCR. RESULTS: Among 96 samples, 26 (27.1%) of them co-expressed SNCG and MMP-9, 30(31.2%) of them expressed neither SNCG nor MMP-9. The expression of SNCG was correlated with the expression of MMP-9 (r = 0.655, P = 0.000).SNCG mRNA level of T47D cell line was 13.5 fold of T47D(SNCG)- cell line and SNCG protein expression was 2.1 fold. While MMP-9 mRNA level of T47D cell line was 7.3 fold of T47D(SNCG)- cell line and MMP-9 protien expression was 1.6 fold.When SNCG was knocked down, the expression of MMP-9 decreased. CONCLUSIONS: SNCG and MMP-9 are significantly correlated with each other in breast cancer. SNCG may promote the invasion and metastasis of breast cancer mediated by up-regulating the expression of MMP-9.

[The effect of breast cancer specific gene 1 in the prognosis of breast cancer].

OBJECTIVE: To detect breast cancer specific gene 1 (BCSG1) expression in different breast tissue, analysis its correlation with clinical parameters and evaluate the prognosis of breast cancer. METHODS: The expression of BCSG1 was detected by reverse transcription-polymerase chain reaction (RT-PCR) in surgical specimens from 84 cases of breast disease patients selected randomly at XinHua Hospital affiliated with Shanghai Second Medical University from September 1999 to December 2002. Of 84 cases, 72 case were breast cancer. Statistic analysis BCSG1 gene expression correlation with clinical parameters of breast cancer. 72 breast cancers were followed up (4 - 43 months) to set up independent prognosis factor by survival analysis. RESULTS: BCSG1 was undetectable in all benign breast lesions, while was detectable in 36.1% of all breast cancer samples (26/72), in which 79.2% of stage III/IV cases were positive (19/24). The expression of BCSG1 was tightly correlated with the stage (P = 0.000) and the size of tumor (P = 0.007). Both ER (P = 0.027) and BCSG1 (P = 0.001) were the independent prognosis factor of breast cancer. CONCLUSION: BCSG1 is one of independent tumor marker of breast cancer, the expression of BCSG1 is closely correlated to the stage of breast cancer and the tumor size. Maybe, BCSG1 is a new prognosis factor of breast cancer.

[Biofeedback therapy for fecal incontinence in patients with mid or low rectal cancer after restorative resection].

OBJECTIVE: To investigate the efficacy of biofeedback therapy for fecal incontinence in patients with mid or low rectal cancer. METHODS: Twenty-four patients with mid or low rectal cancer received biofeedback treatments after restorative resection and therapeutic efficacy was evaluated using anorectal manometry and Vaizey and Wexner scoring systems. Eighteen inpatients without defecating difficulties were selected as control group. RESULTS: The parameters of anorectal manometry in patients with rectal cancer were significantly lower than those in the control group (P<0.01). After biofeedback therapy, the maximum squeeze pressure, resting pressure and maximum tolerated volume were significantly increased, from (118.3+/-42.9) mm Hg to (193.2+/-38.2) mm Hg, (27.8+/-9.0) mm Hg to (47.9+/-9.3) mm Hg,(97.5+/-52.8) ml to (189.1+/-39.0) ml, respectively (all P<0.01), while no significant difference in sensory threshold was observed (P=0.101). Post-treatment Vaizey (10.5+/-2.3 vs 12.9+/-2.8) and Wexner (7.5+/-2.5 vs 10.1+/-2.6) scores were significantly decreased compared with those before biofeedback (P<0.01). CONCLUSION: Biofeedback therapy can improve the anal function in patients with rectal cancer after restorative resection.