Syndecan-2 modulates the YAP pathway in epithelial-to-mesenchymal transition-related migration, invasion, and drug resistance in colorectal cancer.

Epithelial-to-mesenchymal transition (EMT) is associated with an invasive phenotype in colorectal cancer (CRC). Here, we examined the roles of YES-associated protein (YAP) and syndecan-2 (SDC2) in EMT-related progression, invasion, metastasis, and drug resistance in CRC. The expression levels of YAP and SDC2 in CRC patient tumor tissue were quantified by PCR and western blotting. EMT-associated characteristics were assessed using Transwell assays and immunohistochemistry. Co-immunoprecipitation, glutathione S-transferase pull-down, and luciferase reporter assays were used to assess interactions between YAP and SDC2. YAP was found to be highly expressed in tumor tissue from 13/16 CRC patients, while SDC2 was highly expressed in the tumor tissue of 12/16 CRC patients. Overexpression of YAP in colon cancer cells led to increased cell viability, invasion, migration, and oxaliplatin resistance demonstrating that YAP plays a role in EMT. In addition, overexpression of YAP led to decreased expression of the large tumor suppressor kinase 1 (LATS1) and mammalian sterile 20-like kinases (MST1/2). Decreased LATS1 expression was associated with increased levels of cell proliferation. Knockdown of YAP by shRNA interference led to decreased cell invasion, migration, and drug resistance in colon cancer cells and reduced tumorigenesis in a mouse xenograft model. Finally, we established that YAP interacted with SDC2, and demonstrated that SDC2 mediated the YAP pathway through the EMT-related factors BMP4, CTGF and FOXM1.

Clinical efficacy of integral theory-guided laparoscopic integral pelvic floor/ligament repair in the treatment of internal rectal prolapse in females.

BACKGROUND: Internal rectal prolapse (IRP) is one of the most common causes of obstructive constipation. The incidence of IRP in women is approximately three times that in men. IRP is mainly treated by surgery, which can be divided into two categories: Abdominal procedures and perineal procedures. This study offers a better procedure for the treatment of IRP. AIM: To compare the clinical efficacy of laparoscopic integral pelvic floor/ligament repair (IPFLR) combined with a procedure for prolapse and hemorrhoids (PPH) and the laparoscopic IPFLR alone in the treatment of IRP in women. METHODS: This study collected the clinical data of 130 female patients with IRP who underwent surgery from January 2012 to October 2014. The patients were divided into groups A and B. Group A had 63 patients who underwent laparoscopic IPFLR alone, and group B had 67 patients who underwent the laparoscopic IPFLR combined with PPH. The degree of internal rectal prolapse (DIRP), Wexner constipation scale (WCS) score, Wexner incontinence scale (WIS) score, and Gastrointestinal Quality of Life Index (GIQLI) score were compared between groups and within groups before surgery and 6 mo and 2 years after surgery. RESULTS: All laparoscopic surgeries were successful. The general information, number of bowel movements before surgery, DIRP, GIQLI score, WIS score, and WCS score before surgery were not significantly different between the two groups (all P > 0.05). The WCS score, WIS score, GIQLI score, and DIRP in each group 6 mo, and 2 years after surgery were significantly better than before surgery (P < 0.001). In group A, the DIRP and WCS score gradually improved from 6 mo to 2 years after surgery (P < 0.001), and the GIQLI score progressively improved from 6 mo to 2 years after surgery (P < 0.05). In group B, the DIRP, WCS score and WIS score significantly improved from 6 mo to 2 years after surgery (P < 0.05), and the GIQLI score 2 years after surgery was significantly higher than that 6 mo after surgery (P < 0.05). The WCS score, WIS score, GIQLI score, and DIRP of group B were significantly better than those of group A 6 mo and 2 years after surgery (all P < 0.001, Bonferroni) except DIRP at 2 years after surgery. There was a significant difference in the recurrence rate of IRP between the two groups 6 mo after surgery (P = 0.011). There was no significant difference in postoperative grade I-III complications between the two groups (P = 0.822). CONCLUSION: Integral theory-guided laparoscopic IPFLR combined with PPH has a higher cure rate and a better clinical efficacy than laparoscopic IPFLR alone.

Mechanisms of wheat (Triticum aestivum) grain storage proteins in response to nitrogen application and its impacts on processing quality.

Basis for the effects of nitrogen (N) on wheat grain storage proteins (GSPs) and on the establishment of processing quality are far from clear. The response of GSPs and processing quality parameters to four N levels of four common wheat cultivars were investigated at two sites over two growing seasons. Except gluten index (GI), processing quality parameters as well as GSPs quantities were remarkably improved by increasing N level. N level explained 4.2~59.2% and 10.4~80.0% variability in GSPs fractions and processing quality parameters, respectively. The amount of N remobilized from vegetative organs except spike was significantly increased when enhancing N application. GSPs fractions and processing quality parameters except GI were only highly and positively correlated with the amount of N remobilized from stem with sheath. N reassimilation in grain was remarkably strengthened by the elevated activity and expression level of glutamine synthetase. Transcriptome analysis showed the molecular mechanism of seeds in response to N levels during 10~35 days post anthesis. Collectively, we provided comprehensive understanding of N-responding mechanisms with respect to wheat processing quality from N source to GSPs biosynthesis at the agronomic, physiological and molecular levels, and screened candidate genes for quality breeding.

Subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy for the treatment of slow transit constipation in an aged population: A retrospective control study.

AIM: To compare the efficacy, improved quality of life, and prognosis in patients undergoing either subtotal colonic bypass with antiperistaltic cecoproctostomy (SCBAC) or subtotal colonic bypass plus colostomy with antiperistaltic cecoproctostomy (SCBCAC) for the treatment of slow transit constipation. METHODS: Between October 2010 and October 2014, aged patients with slow transit constipation who were hospitalized and underwent laparoscopic surgery in our institute were divided into two groups: the bypass group, 15 patients underwent SCBAC, and the bypass plus colostomy group, 14 patients underwent SCBCAC. The following preoperative and postoperative clinical data were collected: gender, age, body mass index, operative time, first flatus time, length of hospital stay, bowel movements (BMs), Wexner fecal incontinence scale, Wexner constipation scale (WCS), gastrointestinal quality of life index (GIQLI), numerical rating scale for pain intensity (NRS), abdominal bloating score (ABS), and Clavien-Dindo classification of surgical complications (CD) before surgery and at 3, 6, 12, and 24 mo after surgery. RESULTS: All patients successfully underwent laparoscopic surgery without open surgery conversion or surgery-related death. The operative time and blood loss were significantly less in the bypass group than in the bypass plus colostomy group (P = 0.007). No significant differences were observed in first flatus time, length of hospital stay, or complications with CD > 1 between the two groups. No patients had fecal incontinence after surgery. At 3, 6, and 12 mo after surgery, the number of BMs was significantly less in the bypass plus colostomy group than in the bypass group. The parameters at 3, 6, 12, and 24 mo after surgery in both groups significantly improved compared with the preoperative conditions (P < 0.05), except NRS at 3, 6 mo after surgery in both groups, ABS at 12, 24 mo after surgery and NRS at 12, 24 mo after surgery in the bypass group. WCS, GIQLI, NRS, and ABS significantly improved in the bypass plus colostomy group compared with the bypass group at 3, 6, 12, and 24 mo after surgery (P < 0.05) except WCS, NRS at 3, 6 mo after surgery and ABS at 3 mo after surgery. At 1 year after surgery, a barium enema examination showed that the emptying time was significantly better in the bypass plus colostomy group than in the bypass group (P = 0.007). CONCLUSION: Laparoscopic SCBCAC is an effective and safe procedure for the treatment of slow transit constipation in an aged population and can significantly improve the prognosis. Its clinical efficacy is more favorable compared with that of SCBAC. Laparoscopic SCBCAC is a better procedure for the treatment of slow transit constipation in an aged population.

An Overexpressed Q Allele Leads to Increased Spike Density and Improved Processing Quality in Common Wheat (Triticum aestivum).

Spike density and processing quality are important traits in modern wheat production and are controlled by multiple gene loci. The associated genes have been intensively studied and new discoveries have been constantly reported during the past few decades. However, no gene playing a significant role in the development of these two traits has been identified. In the current study, a common wheat mutant with extremely compact spikes and good processing quality was isolated and characterized. A new allele (Qc1 ) of the Q gene (an important domestication gene) responsible for the mutant phenotype was cloned, and the molecular mechanism for the mutant phenotype was studied. Results revealed that Qc1 originated from a point mutation that interferes with the miRNA172-directed cleavage of Q transcripts, leading to its overexpression. It also reduces the longitudinal cell size of rachises, resulting in an increased spike density. Furthermore, Qc1 increases the number of vascular bundles, which suggests a higher efficiency in the transportation of assimilates in the spikes of the mutant than that of wild type. This accounts for the improved processing quality. The effects of Qc1 on spike density and wheat processing quality were confirmed by analyzing nine common wheat mutants possessing four different Qc alleles. These results deepen our understanding of the key roles of Q gene, and provide new insights for the potential application of Qc alleles in wheat quality breeding.

Linoleic acid isomerase gene FgLAI12 affects sensitivity to salicylic acid, mycelial growth and virulence of Fusarium graminearum.

Fusarium graminearum is the major causal agent of fusarium head blight in wheat, a serious disease worldwide. Linoleic acid isomerase (LAI) catalyses the transformation of linoleic acid (LA) to conjugated linoleic acid (CLA), which is beneficial for human health. We characterised a cis-12 LAI gene of F. graminearum (FGSG_02668; FgLAI12), which was downregulated by salicylic acid (SA), a plant defence hormone. Disruption of FgLAI12 in F. graminearum resulted in decreased accumulation of cis-9,trans-11 CLA, enhanced sensitivity to SA, and increased accumulation of LA and SA in wheat spikes during infection. In addition, mycelial growth, accumulation of deoxynivalenol, and pathogenicity in wheat spikes were reduced. Re-introduction of a functional FgLAI12 gene into ΔFgLAI12 recovered the wild-type phenotype. Fluorescent microscopic analysis showed that FgLAI12 protein was usually expressed in the septa zone of conidia and the vacuole of hyphae, but was expressed in the cell membrane of hyphae in response to exogenous LA, which may be an element of LA metabolism during infection by F. graminearum. The cis-12 LAI enzyme encoded by FgLAI12 is critical for fungal response to SA, mycelial growth and virulence in wheat. The gene FgLAI12 is potentially valuable for biotechnological synthesis of cis-9,trans-11 CLA.