Function and mechanism of MCM8 in the development and progression of colorectal cancer.

Colorectal cancer (CRC) has become a global health problem which has almost highest morbidity and mortality in all types of cancers. This study aimed to uncover the biological functions and underlying mechanism of MCM8 in the development and progression of CRC. The expression level of MCM8 was found to be upregulated in CRC tissues and significantly associated with tumor grade and patients' survival. Knocking down MCM8 expression in CRC cells could restrain cell growth and cell motility while promoting cell apoptosis in vitro, as well as inhibit tumor growth in xenograft mice model. Based on the RNA screening performing on CRC cells with or without MCM8 knockdown and the following IPA analysis, CHSY1 was identified as a potential target of MCM8 in CRC, whose expression was also found to be higher in tumor tissues than in normal tissues. Moreover, it was demonstrated that MCM8 may regulate the expression of CHSY1 through affecting its NEDD4-mediated ubiquitination, both of which synergistically execute tumor promotion effects on CRC. In conclusion, the outcomes of our study showed the first evidence that MCM8 act as a tumor promotor in CRC, and may be a promising therapeutic target of CRC treatment.

CNN2 silencing inhibits colorectal cancer development through promoting ubiquitination of EGR1.

Colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumors of the digestive tract. H2-calponin (CNN2), an actin cytoskeleton-binding protein, is an isoform of the calponin protein family whose role in CRC is still unknown. Research based on clinical samples showed the up-regulation of CNN2 in CRC and its association with tumor development, metastasis, and poor prognosis of patients. Both in vitro loss-of-function and gain-of-function experiments showed that CNN2 participates in CRC development through influencing malignant cell phenotypes. In vivo, xenografts formed by CNN2 knockdown cells also showed a slower growth rate and smaller final tumors. Furthermore, EGR1 was identified as a downstream of CNN2, forming a complex with CNN2 and YAP1 and playing an essential role in the CNN2-induced regulation of CRC development. Mechanistically, CNN2 knockdown down-regulated EGR1 expression through enhancing its ubiquitination, thus decreasing its protein stability in a YAP1-dependent manner. In summary, CNN2 plays an EGR1-dependent promotion role in the development and progression of CRC, which may be a promising therapeutic target for CRC treatment.

Enterogenic empyema complicating colobronchial fistula: a case report.

BACKGROUND: Enterogenic empyema is an uncommon complication of colobronchial fistula (CBF). We reported a case of enterogenic empyema patient after surgery for CBF. CASE PRESENTATION: A 66-year-old gentleman presented with persistent fever and repeated hemoptysis for 8 months. Computed tomography of the thorax confirmed the presence of a consolidation mass located in the right middle lobe and an air space near the right rib angle. During exploration, CBF was found. The patient underwent right middle and lower lobectomy together with closure of colonic and diaphragmatic perforation. The colon closure and diaphragm closure ruptured after surgery, leading to enterogenic empyema. Adequate drainage, sustained high protein diet, and antibiotic treatment eventually resulted in full recovery. CONCLUSION: This is the first report of enterogenic empyema complicating CBF.

Silencing of Proteasome 26S Subunit ATPase 2 Regulates Colorectal Cancer Cell Proliferation, Apoptosis, and Migration.

OBJECTIVE: Colorectal cancer (CRC) remains a major cause of cancer-related death worldwide. Proteasome 26S subunit ATPase 2 (PSMC2) plays vital roles in regulating cell cycle and transcription and has been confirmed to be a gene potentially associated with some human tumors. However, the expression correlation and molecular mechanism of PSMC2 in CRC are still unclear. This study aimed to investigate the role of PSMC2 in malignant behaviors in CRC. METHODS: The high protein levels of PSMC2 in CRC samples were identified by tissue microarray analysis. Lentivirus was used to silence PSMC2 in HCT116 and RKO cells; MTT and colony formation assay were performed to determine cell proliferation. Wound healing and Transwell assay were used to detect cell migration and invasion. Flow cytometry assay was applied to detect cell cycle and apoptosis. RESULT: The results showed that, among the 96 CRC patients, the expression of PSMC2 was a positive correlation with the clinicopathological features of the patients with CRC. Furthermore, the low PSMC2 expression group showed a higher survival rate than the high PSMC2 expression group. The expression levels of PSMC2 in cancer tissue were dramatically upregulated compared with adjacent normal tissues. In vitro, shPSMC2 was designed to inhibit the expression of PSMC2 in CRC cells. Compared with shCtrl, silencing of PSMC2 significantly suppressed cell proliferation, decreased single cell colony formation, enhanced apoptosis, and accelerated G2 phase and/or S phase arrest. CONCLUSION: Survival analysis indicated that high expression of PSMC2 in the CRC samples was associated with poorer survival rate than low expression of PSMC2, while the anti-tumor effect of PSMC2 silencing was also confirmed at the cellular level in vitro. Our results suggested that PSMC2 potentially worked as a regulator for CRC, and the silencing of PSMC2 may be a therapeutic strategy for CRC.

Protective effects of hydrogen-rich saline on ulcerative colitis rat model.

BACKGROUND: Ulcerative colitis (UC) is associated with enhanced production of reactive oxygen species and altered angiogenesis. Molecular hydrogen has been documented as a novel antioxidant to treat various reactive oxygen species-related diseases. The present study aimed to investigate the effects of hydrogen on UC using a rat model. MATERIALS AND METHODS: UC in rats was induced with intracolonically administrated acetic acid. Hydrogen was supplied through intraperitoneal injection of 10 or 20 mL/kg hydrogen-rich saline. The hydrogen treatment was performed once every 2 d and lasted 2 wk. The stool consistency and weight loss were used to evaluate UC development. Colonic mucosal damage at the end of the experiment was scored using the macroscopic and microscopic observations. Vascular endothelial growth factor expression in the colonic mucosa was determined using immunohistochemistry. RESULTS: The administration of acetic acid induced acute rat UC, as indicated by diarrhea, weight loss, and colonic mucosal damage. Treatment with hydrogen-rich saline reduced the weight loss and diarrhea and alleviated the colonic mucosal damage in the UC rats. In addition, the expression of vascular endothelial growth factor in the UC rats increased and could be inhibited by hydrogen treatment. CONCLUSIONS: Antioxidative hydrogen-rich saline effectively protected the rats from UC, which might be, at least in part, because of inhibition of vascular endothelial growth factor.

Quantitative anatomical study of male pelvic autonomic plexus and its clinical potential in rectal resection.

The pelvic autonomic nerves innervate the pelvic viscera, and carry a high risk of damage during surgery. This high risk has been ascribed to the complex interrelationship of pelvic paravisceral structures and the difficulty in identifying particular structures, despite the fact that the anatomic characteristics of the pelvic autonomic plexus have been well documented. We dissected ten male embalmed adult cadavers with particular attention to the quantitative parameters of the pelvic plexus and its subsidiary plexus. The right inferior hypogastric plexus and its rectal branch were found to be significantly longer and wider than the left one, while the transverse diameter of the vesical and prostatic branches of the left side was significantly larger the right. The inferior mesenteric plexus gave off fibers directly to form the pelvic plexus in four of 20 hemipelves (20%). In the side-by-side comparison, the distance to midpoint of the sacral promontory of the left rectal plexus was significantly longer than that of the right, whereas the maximum length (the length of the longest nerve fiber from origin to corresponding organ) of the left vesical plexus was significantly shorter than that of the right. Additionally, the craniocaudal and dorsoventral diameters of the right pelvic autonomic plexus were significantly shorter those of the left. The quantitative parameters relating to the pelvic autonomic plexuses not only can enhance our understanding of its anatomy and function, but can also be used as references for surgical procedures and robot-assisted surgery.