Gingerenone A Attenuates Ulcerative Colitis via Targeting IL-17RA to Inhibit Inflammation and Restore Intestinal Barrier Function.

Ulcerative colitis (UC) is a complicated and recurrent intestinal disease. Currently available drugs for UC treatment are scarce, therefore, novel therapeutic drugs for the UC are urgently to be developed. Gingerenone A (GA) is a phenolic compound known for its anti-inflammatory effect, but its effect on UC remains unknown. Here, it is shown that GA protects mice against UC, which is closely associated with inhibiting intestinal mucosal inflammation and enhancing intestinal barrier integrity in vivo and in vitro. Of note, RNA sequencing analysis demonstrates an evident correlation with IL-17 signaling pathway after GA treatment, and this effect is further corroborated by Western blot. Mechanistically, GA directly interacts with IL-17RA protein through pull-down, surface plasmon resonance analysis and molecular dynamics simulation. Importantly, lentivirus-mediated IL-17RA/Act1 knock-down or GA co-treatment with brodalumab/ixekizumab significantly impairs the protective effects of GA against DSS-induced inflammation and barrier dysfunction, suggesting a critical role of IL-17RA signaling for GA-mediated protection against UC. Overall, these results indicate that GA is an effective agent against UC mainly through the direct binding of IL-17RA to inhibit inflammatory signaling activation.

Integrating cfDNA liquid biopsy and organoid-based drug screening reveals PI3K signaling as a promising therapeutic target in colorectal cancer.

BACKGROUND: The current precision medicine relies on biomarkers, which are mainly obtained through next-generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. This study tried to combine liquid biopsy with functional drug tests using organoid models to find potential drugs for cancer patients. METHODS: Colorectal cancer (CRC) patients were prospectively enrolled and blood samples were collected from patients before the start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models. RESULTS: A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients. CONCLUSION: Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.

Spindle function and Wnt pathway inhibition by PBX1 to suppress tumor progression via downregulating DCDC2 in colorectal cancer.

PBX1 is a transcription factor that regulates a variety of genes, involved in intracellular lipid metabolism, cell proliferation, and other pathways. The promoting and inhibiting function of PBX1 in various cancer types was extensively discussed, however, there have been no studies on PBX1 proteins in colorectal cancer (CRC). This study aimed to reveal the anti-tumor function of PBX1 in CRC and the underlying molecular mechanism. Bioinformatics analysis revealed that PBX1 is downregulated in CRC, indicating that is a potential antioncogene in CRC. Overexpression of PBX1 suppresses tumor growth and metastasis in vitro and in vivo. Mechanistically, we found that PBX1 acted as a transcription factor that suppressed DCDC2 expression and inhibited spindle function. Moreover, the PBX1-DCDC2 axis controlled the Wnt pathway in CRC cells. Overexpression of DCDC2 restored CRC proliferation, metastasis abilities and Wnt pathway. In conclusion, this study suggests that PBX1 acts as a transcription factor to suppress DCDC2 expression and inhibit cell proliferation and metastasis by disrupting spindle function and the Wnt pathway in CRC.

CircMMP1 promotes colorectal cancer growth and metastasis by sponging miR-1238 and upregulating MMP family expression.

BACKGROUND: Circular RNAs (circRNAs) are a type of non-coding RNA which play an important role in the regulation of biological processes of various malignant tumors. However, the potential molecular mechanisms and roles of circRNAs in colorectal cancer (CRC) remain unelucidated. METHODS: In the current study, we analyzed the data of high-throughput microarray sequencing to screen differentially expressed circRNAs in CRC. Cell counting kit-8 (CCK-8), colony-formation, transwell, mouse xenograft models and immunohistochemistry assays were used to explore the function of circRNAs. TargetScan database, quantitative real-time polymerase chain reaction (qRT-PCR), double luciferase and RNA immunoprecipitation (RIP) were used to explore the molecular mechanism. RESULTS: We identified circMMP1 (hsa_circ_0024109) as a frequently upregulated circRNA in both CRC tissues and cells. Both in vitro and in vivo experiments demonstrated that circMMP1 knockdown significantly inhibited the proliferation and metastasis of CRC. The results demonstrated that circMMP1 promoted the growth and metastasis of CRC by sponging miR-1238 and upregulating the expression of matrix metalloproteinase 1 (MMP1), MMP2, and MMP9 expression. CONCLUSIONS: In conclusion, our study identified the biological role of the circMMP1-miR-1238-MMP1/MMP2/MMP9 axis in the growth and metastasis of CRC, which is crucial for the monitoring and treatment of CRC. Further research on circMMP1 may provide a theoretical basis for diagnostic biomarkers of early CRC screening.

HSPA4 Knockdown Retarded Progression and Development of Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is a common malignancy associated with high morbidity and mortality. Heat shock 70 kDa protein 4 (HSPA4) has been shown to exert regulatory roles during tumor progression in different cancer types. Here, we investigated the expression and cellular functions of HSPA4 in CRC. MATERIALS AND METHODS: Expression of HSPA4 in CRC tissues and paracancerous tissues was analyzed by RT-qPCR and immunohistochemistry IHC staining. The functional roles of HSPA4 were explored using shRNA-mediated knockdown in HCT116 and RKO CRC cell lines, both in vitro and in tumor xenograft studies. RESULTS: HSPA4 expression was significantly increased at the RNA and protein levels in CRC tissues compared with noncancerous tissues. Moreover, HSPA4 expression was positively associated with tumor stage and its high expression of HSPA4 indicated poor patient prognosis. In vitro studies established that HSPA4 knockdown inhibited proliferation and migration, causing arrest in the G2-phase of the cell cycle along with increased levels of apoptosis. This phenotype was recapitulated in vivo where HSPA4 knockdown suppressed xenograft growth. Mechanistic investigations showed silencing of HSPA4 reduced activation of the PI3K, Akt signaling axis while also downregulating the cell cycle progression markers, CCND1 and CDK6. Similarly, there was altered expression of apoptosis-related proteins consistent with the increase in apoptosis. CONCLUSION: Our findings demonstrate clinical significance for HSPA4 in CRC, further showing that HSPA4 contributes to CRC tumorigenesis through effects on proliferation, migration and survival. Thus, HSPA4 represents a novel prognostic indicator as well as a promising therapeutic target in CRC.

A Substage Increase in The AJCC Classification System Improves Prognostic Prediction in Stage III Gastric Cancer With Insufficient Lymph Nodes Removed.

BACKGROUND: The impact of lymph nodes (LNs) removed on the survivals of patients with stage III gastric cancer, especially on that of those who undergo the adjuvant chemotherapy as a compensation for a possibly insufficient lymphadenectomy, is still unclear. METHODS: Consecutive patients (n = 488) with stage III gastric cancer under R0 curative resection followed by adjuvant chemotherapy were analyzed. The overall survival (OS) was compared between patients with insufficient LNs removed (ILNr, <16 LNs) and sufficient LNs removed (SLNr, ≥16 LNs). Performance of the prediction systems was evaluated using the Likelihood ratio χ2 test, Akaike information criterion (AIC), Harrell's concordance index (C-index), and area under the receiver operating characteristic curves (AUC). RESULTS: The OS of patients were significantly longer in those with SLNr relative to those with ILNr (for stage IIIA, 68.2 vs. 43.2 months, P = 0.042; for stage IIIB, 43.7 vs. 24.9 months, P < 0.001; for stage IIIC, 23.9 vs. 8.3 months, P < 0.001; and for total stage III, 37.7 vs. 21.7 months, P < 0.001). However, the OS were similar between stage IIIA patients with ILNr and stage IIIB patients with SLNr (P = 0.928), between IIIB patients with ILNr and IIIC patients with SLNr (P = 0.962), and IIIC patients with ILNr and stage IV (P = 0.668), respectively. A substage increase in the AJCC classification system, from IIIA to IIIB, from IIIB to IIIC, and from IIIC to IV in patients with ILNr, enhanced the accuracy of prognostic prediction in patients with stage III gastric cancer compared to the current TNM system (Likelihood ratio χ2, 188.6 vs. 184.8; AIC, 4336.4 vs. 4340.6; C-index, 0.695 vs. 0.679, P = 0.002). The ROC curves revealed that the performance of prognostic prediction was better in the new prediction system (AUC = 0.699) compared with the current TNM system (AUC = 0.676). CONCLUSIONS: ILNr (LNs <16) impairs the long-term outcomes of stage III gastric cancer underwent adjuvant chemotherapy. The status of LNs removal adds values to the current TNM system in prognostic prediction of stage III gastric cancer.

Extensive Dissection at No. 12 Station During D2 Lymphadenectomy Improves Survival for Advanced Lower-Third Gastric Cancer: A Retrospective Study From a Single Center in Southern China.

BACKGROUND: D2 lymphadenectomy including No. 12a dissection has been accepted as a standard surgical management of advanced lower-third gastric cancer (GC). The necessity of extensive No. 12 nodes (No. 12a, 12b, and 12p) dissection remains controversial. This study aims to explore its impact on long-term survival for resectable GC. METHODS: From 2009 to 2016, 353 advanced lower-third GC patients undergoing at least D2 lymphadenectomy during a radical surgery were included, with 179 patients receiving No. 12a, 12b, and 12p dissection as study group. A total of 174 patients with No. 12a dissection were employed as control group. Surgical and long-term outcomes including 90-day complications incidence, therapeutic value index (TVI), 3-year progression-free survival (PFS), and 5-year overall survival (OS) were compared between both groups. RESULTS: No. 12 lymph node metastasis was observed in 20 (5.7%) patients, with 10 cases in each group (5.6% vs. 5.7%, p = 0.948). The metastatic rates at No. 12a, 12b, and 12p were 5.7%, 2.2%, and 1.7%, respectively. The incidence of 90-day complications was identical between both groups. Extensive No. 12 dissection was associated with increased TVI at No. 12 station (3.9 vs. 0.6), prolonged 3-year PFS rate (67.0% vs. 55.9%, p = 0.045) and 5-year OS rate (66.2% vs. 54.0%, p = 0.027). The further Cox-regression analysis showed that the 12abp dissection was an independent prognostic factor of improved survival (p = 0.026). CONCLUSION: Adding No. 12b and 12p lymph nodes to D2 lymphadenectomy might be effective in surgical treatment of advanced lower-third GC and improve oncological outcomes compared with No. 12a-based D2 lymphadenectomy.

MicroRNA-674-5p induced by HIF-1α targets XBP-1 in intestinal epithelial cell injury during endotoxemia.

Intestinal mucosal integrity dysfunction during endotoxemia can contribute to translocation of intestinal bacteria and a persistent systemic inflammatory response, which both fuel the pathophysiological development of sepsis or endotoxemia. The pathogenesis of intestinal damage induced by endotoxemia remains poorly understood. Here, we identified the microRNA (miR)-674-5p/X-box binding protein 1 (XBP-1) axis as a critical regulator and therapeutic target in preventing intestinal crypt cell proliferation during endotoxemia. MiR-674-5p was markedly increased in intestinal epithelial cells (IECs) during endotoxemia and its induction depended on hypoxia-inducible factor-1α (HIF-1α). Intriguingly, gene expression microanalysis revealed that expression of XBP-1 was down-regulated in IECs with over-expression of miR-674-5p. miR-674-5p was found to directly target XBP-1 protein expression. Upon in vitro, anti-miR-674-5p enhanced sXBP-1 expression and facilitated intestinal crypt cell proliferation. Blockade of miR-674-5p promoted XBP-1 activity, attenuated intestinal inflammation, and expedited intestinal regeneration, resulting in protection against endotoxemia-induced intestinal injury in mice. More importantly, the survival in endotoxemia mice was significantly improved by inhibiting intestinal miR-674-5p. Collectively, these data indicate that control of a novel miR-674-5p/XBP-1 signaling axis may mitigate endotoxemia -induced intestinal injury.

Aberrant AFP expression characterizes a subset of hepatocellular carcinoma with distinct gene expression patterns and inferior prognosis.

Background Serum tumor markers are ubiquitously used in the clinic for cancer screening. However, the mechanisms accounting for the elevated levels of the serum tumor markers remain to be explored. Methods We performed a pan-cancer analysis of serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA). The relation between concentration of serum tumor markers and the expression of their coding genes was assessed. Then the expression of AFP and its genomic background in hepatocellular carcinoma (liver cancer) was studied. Results High expression of AFP mRNA was found mainly in liver cancer. In gastric cancer, breast cancer and lung cancer, high AFP mRNA expression was also discovered occasionally. In liver cancer patients, serum AFP levels correlated significantly with AFP mRNA expression in cancer tissues (r = 0.72, p = 1.6e-45). Whole transcriptome analysis revealed that serum AFP levels clearly separated liver cancer into two classes with distinct expression profiles according to PCA analysis. Gene co-expression analysis revealed that AFP expression was connected to a module enriched with genes accounting for cell cycle and cell proliferation regulation. In addition, high AFP expression was associated with the molecular classification of liver cancer, including iCluster (Chi-square: 16.86, P = 0.0002). Methylation analysis revealed de-methylation of AFP promoter occurred in some liver cancer tissues, which was significantly related to AFP mRNA expression. Survival analysis indicated high serum AFP levels was prognostic of poorer survival of the liver cancer patients (Log-rank test: p = 0.046). This was confirmed by an independent dataset in which liver cancer patients with high serum AFP also had poorer survival (Log-rank test: p = 0.024). Conclusion High expression of AFP defined a subtype of liver cancer with distinct gene expression profiles and clinical features. De-methylation of cytosine from CpG di-nucleotides in AFP promoter may be the cause of AFP re-expression in adult human liver cancer tissue.

Transcriptomic analysis reveals that heat shock protein 90α is a potential diagnostic and prognostic biomarker for cancer.

The molecular chaperone heat shock protein 90 (Hsp90) is highly expressed in tumor tissue according to many studies. However, there is no large-scale study investigating the expression of Hsp90 in pan-cancer so far, and the molecular mechanisms leading to aberrant Hsp90 expression are also largely unknown. To address these questions, we performed an in silico analysis of Hsp90 expression using mRNA sequencing data from The Cancer Genome Atlas study. The results were further validated using independent datasets. We found that the expression of HSP90AA1, a subtype of Hsp90, was much higher in hepatocellular carcinoma than in adjacent normal liver tissue. A large cancer panel with eight more cancer types revealed a similar trend except for prostate cancer, which had low HSP90AA1 expression in tumor tissue. Heat shock factor 1 followed a similar trend as HSP90AA1, with higher expression in cancer. HSP90AA1 expression was closely related to its copy numbers. Deletion of the HSP90AA1 locus in a subset of hepatocellular carcinoma led to low HSP90AA1 expression. In addition, higher HSP90AA1 expression was associated with poorer prognosis in hepatocellular carcinoma patients. In a multivariable analysis including tumor, node and metastasis stage, HSP90AA1 expression remained a negative prognostic factor, suggesting that the effect of HSP90AA1 was independent of tumor stage. In conclusion, we demonstrated that high HSP90AA1 expression was ubiquitous in cancer and that HSP90AA1 was a potential diagnostic and prognostic biomarker for hepatocellular carcinoma.

Two cases of small bowel obstruction due to a shiitake mushroom.

The shiitake mushroom (Lentinula edodes), known as Xiang-gu in China, has been an important component of Asian cuisine for hundreds of years. Although not easily digestible, there are few reports of them causing bowel obstruction. We present two cases of small bowel obstruction due to a shiitake mushroom requiring surgical intervention. Two patients who did not have any teeth and did not use dentures presented with intestinal bowel obstruction and were referred to the Emergency Department of our hospital after eating a meal including shiitake mushrooms without cutting. The first patient underwent an emergency laparotomy and a semental small bowel resection and the other underwent laparoscopic small bowel incision for removal of a foreign body. The causes of the small bowel obstruction for the two patients were uncut shiitake mushrooms in the small bowel. The two patients recovered uneventfully post-operatively.

Designing a castor oil-based polyurethane as bioadhesive.

Based on the stealth behavior of castor oil and poly(ethylene glycol), we selected a polyurethane system to obtain an ideal surgical adhesive. The polyurethane adhesives with varying concentrations of castor oil were investigated by Fourier transform infrared spectrometer, differential scanning calorimetry, scanning electron microscopy, goniometer, and universal testing machine. Curing results show that a 7-min to 25-min room temperature curing can be achieved, providing one possibility of shortening the surgery time. In vitro biodegradation test demonstrates that a certain proportion of the polyurethane film will be hydrolyzed in a foregone manner after a period of time (7 weeks). The adhesion strengths of these adhesives show a strong bonding between pieces of tissue, which makes them qualified for application in a moist environment.

Elevated expression of CXCL16 correlates with poor prognosis in patients with colorectal cancer.

Aims: To examine the expression of CXCL16 in colorectal cancer (CRC) tissue and to clarify the relationships between CXCL16 and clinicopathological features and survival in CRC. Methods: A total of 142 consecutive CRC patients undergoing colorectal surgery at the Department of Gastrointestinal Center, First Affiliated Hospital, Sun Yat-sen University, between January 2010 and December 2010 were enrolled in this study. CXCL16 was measured by immunohistochemical staining in CRC tissue. Association between CXCL16 expression and clinicopathologic parameters was analyzed with a chi-square test. Survival curves were calculated by the Kaplan-Meier method, and the differences between CXCL16 high- and low-expression groups were analyzed using the log-rank test. Cox univariate and multivariate analyses were used to determine risk factors for overall survival (OS). Results: CXCL16 expression was elevated in CRC. CXCL16-positive expression was significantly related to tumor size (P=0.043), tumor differentiation (P=0.046) and distant metastasis (P=0.038), and there was a trend toward lymph node metastasis (P=0.070). CXCL16 expression, together with differentiation, depth of invasion, lymph node metastasis, and distant metastasis, was a significant independent prognostic factor for OS of patients with CRC (HR 2.026, 95% CI 1.128-3.640, P=0.018). Conclusion: CXCL16 expression was enhanced in CRC tissue and was negatively correlated with survival in CRC patients. Furthermore, CXCL16-positive expression was an independent prognostic factor for CRC patients, whilst the underlying mechanisms remain unclear; thus, further studies are needed.

Downregulation of DPF3 promotes the proliferation and motility of breast cancer cells through activating JAK2/STAT3 signaling.

It is reported that the genetic variation of DPF3 is a risk factor of breast cancer through large-scale association research. However, the expression, function and mechanism in breast cancer is unknown. We applied qPCR and western blotting to detect the levels of DPF3 in breast cancer tissues. MTT and Anchorage-independent growth ability assay were used to evaluate the effect of DPF3 on cell proliferation. Wound healing and transwell invasion assay were performed to detect the role of DPF3 on cell motility ability. Herein, we found that the mRNA and protein levels of DPF3 are both significantly downregulated in breast cancer tissues. And downregulation of DPF3 can promote the proliferation and motility of breast cancer cells. Further investigation illustrated that downregulation of DPF3 can activate the JAK2/STAT3 signaling. In conclusion, we found that the downregulation of DPF3 plays an indispensable function in the progression of breast cancer, and may be served as a novel therapeutic target to therapy breast cancer.

Does Lymphadenectomy with at Least 15 Perigastric Lymph Nodes Retrieval Promise an Improved Survival for Gastric Cancer: A Retrospective Cohort Study in Southern China.

Background: Specific guidelines recommend at least 15 or 16 lymph nodes (LNs) be examined to adequately assess nodal category of gastric cancer (GC), but the requirement for minimum number of regional LNs retrieval is not mentioned. This study aims to investigate survival significance from various numbers of perigastric (N1) LNs retrieval and to determine an optimal number harvested in such region. Study design: From April 1994 to March 2012, 1003 resectable GC patients with at least 15 LNs examined were included. Patients with at least 15 N1 nodes retrieval were assigned into study group, with the rest into control group. The 5-year overall survival (OS) rate was compared between two groups, and an optimal number of examined N1 nodes was detected by a survival joinpoint analysis. Results: 635 (63.3%) patients in study group had median 22 (range, 15-75) N1 nodes and 3 (range, 0-74) positive N1 nodes retrieval, with median 10 (range, 0-14) N1 nodes and 1 (range, 0-29) metastatic N1 nodes examined in control group. The number of N1 nodes retrieval was associated with tumor location (P=0.007), tumor stage (P<0.001) and total number of harvested LNs ( r =0.691, P<0.001). Median survival time (79.0 vs. 72.0 months, P=0.462) and actual 5-year OS rate (41.0% vs. 39.2%, P=0.463) were slightly improved in study group compared with control group, with significance obtained via stage-by-stage analysis. The joinpoint analysis indicated that at least seven N1 nodes retrieval achieved survival significance (81.0 vs. 35.0 months, P=0.036), with survival superiority remained until reaching up to 15 N1 nodes. Conclusion: Adequate retrieval of perigastric LNs is essential for radical gastrectomy. A harvest of at least 7-15 perigastric LNs could achieve long-term survival benefit for GC patients.

Deperitoneum biological mesh repair for abdominal wall hernia: a novel wound healing promotion idea.

PURPOSE: Nowadays, biological matrix has become more widely applied than synthetic mesh for the surgical management of ventral hernia. Conventionally, such biodegradable matrix is commonly placed in an intraperitoneal or extraperitoneal position to reinforce the abdominal wall during surgery. Herein, we introduce our novel idea to deliver such biological material. MATERIAL AND METHODS: After contrast-enhanced CT-scan via lateral decubitus confirmed the position of ventral hernias, 11 patients underwent deperitoneum biological mesh repair by open or laparoscopic approach. During surgery, biological material was placed in preperitoneal position with elimination of matrix-covered peritoneum meanwhile. No bridge repair was allowed for this technique. Postoperative complications were prospectively documented. RESULTS: Laparoscopic and open repair were performed in six and five patients, respectively. The mean operative time was 115 min, with no significant difference between the two procedures. All patients had quick recovery and returned to their normal life, with median five days (range, 3-12 days) of hospital stay after surgery. Although wound dehiscence and chronic pain occurred in three (27.3%) patients, no additional surgery was required. No recurrence case was observed within the one-year follow-up period. CONCLUSION: This novel approach could be safely performed in ventral hernia patients. Early evaluation of this surgical technique demonstrates quick recovery and minimal complications.

The mTORC1 signaling modulated by intracellular C3 activation in Paneth cells promotes intestinal epithelial regeneration during acute injury.

Complement activation is associated with regional inflammation during acute gastrointestinal injury (AGI). This study is designed to explore how intracellular C3 activation in Paneth cells (PCs) affects regeneration of intestinal epithelium during AGI. AGI was induced in wildtype C57BL/6 mice, with sham operation employed as control. Exogenous C3 (1 mg, I.P.) was applied at 6 h post-surgery. Intestinal crypts harvested from ileum were cultured with presence or absence of C3 (20 µg/ml), with small interfering RNA against BST1 and complement activation inhibitor selectively applied in vitro. The intestinal integrity, percentage of PCs and intestinal stem cells (ISCs) were evaluated. Importantly, cADPR, C3 fragments, and S6-related proteins were detected in PCs to inspect the mammalian target of rapamycin complex 1 (mTORC1) signaling. AGI caused breakdown of intestinal mucosa integrity and regional inflammation. Exogenous C3 by itself failed to promote the growth of intestinal epithelium, but distinctly enhanced the activity of PCs via intracellular activation, which subsequently supported the expansion of ISCs inside of intestinal crypts. Inhibition of C3 activation was associated with decreased expressions of S6, S6K1 and cADPR, with blocking BST1 found to depress cADPR only. Collectively, these data confirmed intracellular activation of C3 in PCs enhanced expansion of ISCs in response to acute injury. The mTORC1 signaling pathway in PCs contributed to this crosstalk during exogenous C3 treatment.

Long noncoding RNA B3GALT5-AS1 suppresses colon cancer liver metastasis via repressing microRNA-203.

Long noncoding RNAs (lncRNAs) are implicated in various cancers, including colon cancer. Liver metastasis is the main cause of colon cancer-related death. However, the roles of lncRNAs in colon cancer liver metastasis are still largely unclear. In this study, we identified a novel lncRNA B3GALT5-AS1, which is reduced in colon cancer tissues and further reduced in colon cancer liver metastasis tissues. Reduced expression of B3GALT5-AS1 is associated with liver metastasis and poor outcome of colon cancer patients. Gain-of-function and loss-of-function assays revealed that B3GALT5-AS1 inhibited proliferation but promoted migration and invasion of colon cancer cells. Further investigation revealed that B3GALT5-AS1 directly bound to the promoter of miRNA-203, repressed miR-203 expression, upregulated miR-203 targets ZEB2 and SNAI2, and induced epithelial-to-mesenchymal transition (EMT). In vivo study revealed that B3GALT5-AS1 suppressed colon cancer liver metastasis via its binding on miR-203 promoter and the repression of miR-203. miR-203 is increased and epithelial phenotype is preferred in colon cancer liver metastasis tissues. Collectively, our data revealed the suppressive roles of B3GALT5-AS1/miR-203/EMT regulation axis in colon cancer liver metastasis. Our data suggested that the activating B3GALT5-AS1/miR-203/EMT axis may be potential therapeutic strategy for colon cancer liver metastasis.

Influence of marital status on small intestinal adenocarcinoma survival: an analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

AIM: No studies have been published on the relationship between marital status and outcomes in small intestinal cancers. The present study was conducted to explore the influence of marital status on small intestinal adenocarcinoma survival based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Data from eligible patients diagnosed with small intestinal adenocarcinoma between 2004 and 2015 were extracted from the SEER database. Patients were categorized into married group (including common law) and unmarried group (including single [never married], widowed, divorced, separated, and unmarried or domestic partner). The primary endpoints were 5-year overall survival (OS) and 5-year cancer-specific survival (CSS). A survival curve was generated by the Kaplan-Meier method, and the survival rate differences were estimated by a log-rank test. A multivariate Cox proportional hazard model was used to evaluate the independent risk factors for survival. RESULTS: A total of 6,747 small intestinal adenocarcinoma patients were enrolled, including 3,862 married and 2,885 unmarried patients. The 5-year OS and 5-year CSS were significantly greater in married patients than in unmarried patients (27.1 vs 18.8% for OS and 45.7 vs 39.3% for CSS, both P<0.001). After adjusting for age, insurance status, tumor primary site, TNM stage, tumor grade, tumor histology, and surgery, the multivariate Cox proportional hazards model showed that marriage is an independent protective factor for OS (HR =0.789, 95% CI: 0.745-0.836, P<0.001) and CSS (HR =0.794, 95% CI: 0.736-0.857, P<0.001). CONCLUSION: Married small intestinal adenocarcinoma patients have better OS and CSS than unmarried patients. Psychological and economic supports from the spouses of married patients may contribute to improvements in survival.

Laparoscopic right hemicolectomy oriented by superior mesenteric artery for right colon cancer: efficacy evaluation with a match-controlled analysis.

BACKGROUND: Laparoscopic right hemicolectomy (LRC) with a principle of D3 lymphadenectomy seems to be appropriate in treatment of right-sided colon cancer (RCC). This study aimed to evaluate clinical efficacy of superior mesenteric artery (SMA)-guided LRC (SLRC) for RCC patients. PATIENTS AND METHODS: Data for RCC patients with radical resection were retrieved from our database and electronic medical records (January 2010 to December 2014). Patients undergoing SLRC procedure were compared with those undergoing conventional laparoscopic right hemi-colectomy (CLRC), with a match ratio of 1:2 for group balance. Perioperative and long-term outcomes were compared between two groups. RESULTS: In sum, 102 matched patients were selected, with a median follow-up of 32 (range, 3-68) months. The mean operative time was significantly reduced in the SLRC group compared to the CLRC group (206.9 vs 240.0 minutes, P=0.007), with increased incidence of postoperative complications observed (14.7% vs 8.8%, P=0.499). Average length of stay after surgery (7.4 vs 8.0 days), estimated blood loss (85.3 vs 105.4 mL), number of harvested (28.4 vs 28.2) and positive (0.6 vs 0.9) lymph nodes, and overall costs ($4826.9 vs $4874.6) were comparable between two groups (P>0.05). The 3-year disease-free survival rate (89.4% vs 92.1%, P=0.840) and overall survival rate (93.0% vs 83.1%, P=0.273) were similar in both groups. Older age (≥65 years, P=0.049) and advanced tumor stage (≥II, P=0.009) were independent risk factors of recurrence. CONCLUSION: The perioperative and oncologic outcomes of SLRC were not superior, but comparable to CLRC. SMA-guided dissection was a feasible surgical approach in treatment of RCC.