Dissecting the Mechanisms of Intestinal Immune Homeostasis by Analyzing T-Cell Immune Response in Crohn's Disease and Colorectal Cancer.

INTRODUCTION: Crohn's disease (CD) and colorectal cancer (CRC) represent a group of intestinal disorders characterized by intricate pathogenic mechanisms linked to the disruption of intestinal immune homeostasis. Therefore, comprehending the immune response mechanisms in both categories of intestinal disorders is of paramount significance in the prevention and treatment of these debilitating intestinal ailments. METHOD: IIn this study, we conducted single-cell analysis on paired samples obtained from primary colorectal tumors and individuals with Crohn's disease, which was aimed at deciphering the factors influencing the composition of the intestinal immune microenvironment. By aligning T cells across different tissues, we identified various T cell subtypes, such as γδ T cell, NK T cell, and regulatory T (Treg) cell, which maintained immune system homeostasis and were confirmed in enrichment analyses. Subsequently, we generated pseudo-time trajectories for subclusters of T cells in both syndromes to delineate their differentiation patterns and identify key driver genes Result: Furthermore, cellular communication and transcription factor regulatory networks are all essential components of the intricate web of mechanisms that regulate intestinal immune homeostasis. The identified complex cellular interaction suggested potential T-lineage immunotherapeutic targets against epithelial cells with high copy number variation (CNV) levels in CD and CRC. CONCLUSION: Finally, the analysis of regulon networks revealed several promising candidates for cell-specific transcription factors (TFs). This study focused on the immune molecular mechanism under intestinal diseases. It contributed to the novel insight of depicting a detailed immune landscape and revealing T-cell responding mechanisms in CD and CRC.

Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.

BACKGROUND: The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES: The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS: This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS: In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION: E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).

Effect of Nb Content and Second Heat Cycle Peak Temperatures on Toughness of X80 Pipeline Steel.

The microstructure evolution and variation of impact toughness in the heat-affected zone (HAZ) of X80 pipeline steel with different Nb content under different peak temperatures in the secondary thermal cycle were studied through welding thermal simulation, the Charpy impact test, EBSD analysis, SEM observation, and TEM observation in this study. The results indicate that when the peak temperatures of the second pass were lower than Ac1, both X80 pipeline steels had high impact toughness. For secondary peak temperatures in the range of Ac1 to Ac3, both X80 pipeline steels had the worst impact toughness, mainly due to the formation of massive blocky M-A constituents in chain form on grain boundaries. When the secondary peak temperatures were higher than Ac3, both X80 pipeline steels had excellent impact toughness. Smaller grain size and higher proportions of HAGBs can effectively improve the impact toughness. Meanwhile, high Nb X80 pipeline steel had higher impact absorption energy and smaller dispersion. Adding an appropriate amount of Nb to X80 pipeline steel can ensure the impact toughness of SCCGHAZ and SCGHAZ in welded joints.

Effect of early achievement of energy target by different nutritional support strategies on nosocomial infections in patients undergoing major abdominal surgery: a secondary analysis of two randomized clinical trials.

BACKGROUND: The effect of early achievement of energy targets (EAETs) using different nutritional support strategies in patients undergoing major abdominal surgery is unclear. This study determined the impact of EAETs on the incidence of nosocomial infections in patients undergoing major abdominal surgery. METHODS: This was a secondary analysis of two open-label randomized clinical trials. Patients from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and at nutritional risk (Nutritional risk screening 2002≥3) were divided into two groups based on whether they met the 70% energy targets, the EAET (521 EAET and non-achievement of energy target (114 NAET) groups. The primary outcome was the incidence of nosocomial infections between postoperative day 3 and discharge, and the secondary outcomes were actual energy and protein intake, postoperative noninfectious complications, intensive care unit admission, mechanical ventilation, and hospital stay. RESULTS: Overall, 635 patients [mean (SD) age, 59.5 (11.3) years] were included. The EAET group received more mean energy between days 3 and 7 than the NAET group (22.7±5.0 vs. 15.1±4.8 kcal/kg/d; P <0.001). The EAET group had significantly fewer nosocomial infections than the NAET group [46/521(8.8%) vs. 21/114(18.4%); risk difference, 9.6%; 95% CI, 2.1-17.1%; P =0.004]. A significant difference was found in the mean (SD) number of noninfectious complications between the EAET and NAET groups [121/521(23.2%) vs. 38/114(33.3%); risk difference, 10.1%; 95% CI, 0.7-19.5%; P =0.024]. The nutritional status of the EAET group was significantly improved at discharge compared with the NAET group ( P <0.001), and other indicators were comparable between groups. CONCLUSION: EAETs was associated with fewer nosocomial infections and improved clinical outcomes, regardless of the nutritional support strategy (early enteral nutrition alone or combined with early supplemental parenteral nutrition).

Microstructures and Fatigue Properties of High-Strength Low-Alloy Steel Prepared through Submerged-Arc Additive Manufacturing.

Submerged arc additive manufacturing (SAAM) is a viable technique for manufacturing large and complex specialized parts used in structural applications. At present, manufacturing high-strength low-alloy steel T-branch pipe through SAAM has not been reported. This paper uses this technology to manufacture low-alloy structural steel parts. The microstructures of the samples were characterized, which revealed that they were mainly composed of polygonal ferrites. The tensile properties in the horizontal and vertical directions of deposits were studied. Results show that the horizontal tensile strength of deposits was quite close to the vertical one, while the elongation rate in the vertical direction was obviously lower than that in the horizontal direction. Fatigue results indicate that the strain fatigue limit of high-strength low-alloy steel samples in vertical direction was 0.24%. The fatigue fractures of fatigue samples of deposits showed multi-source crack initiation characteristics and the crack propagation regions exhibited typical fatigue striations, so the final instantaneous fracture region showed a ductile fracture. Fatigue performance is very important for the safe service of structural parts, but there is a lack of relevant research on this additive manufacturing part. The results of this paper may support the popularization of the SAAM for high-strength low-alloy steel T-branch pipe.

Poor Pre-operative Nutritional Status Is a Risk Factor of Post-operative Infections in Patients With Gastrointestinal Cancer-A Multicenter Prospective Cohort Study.

Objective: This study aimed to assess the prognostic value of the Nutritional Risk Score 2002 (NRS2002) and patient-generated subjective global assessment (PG-SGA) for post-operative infections in patients with gastric cancer (GC) and colorectal cancer (CRC) who underwent curative surgery. Methods: This prospective study included 1,493 GC patients and 879 CRC patients who underwent curative surgery at 18 hospitals in China between April 2017 and March 2020. The NRS2002 and PG-SGA were performed on the day of admission. The relationship between the nutritional status of patients before surgery and post-surgical incidence of infection was analyzed using univariate and multiple logistic regression analyses. Results: According to NRS2002, the prevalence of nutritional risk was 51.1% in GC patients and 63.9% in CRC patients. According to the PG-SGA, 38.9% of GC patients and 54.2% of CRC patients had malnutrition. Approximately 4.4% of the GC patients and 9.9% of the CRC patients developed infectious complications after surgery. The univariate and multiple logistic regression analyses showed that the risk of infections was significantly higher in GC patients with a high nutritional risk score (NRS2002 ≥5) than in those with a low score (NRS2002 <3), and the PG-SGA score was identified as a predictor of post-operative infection complications of CRC. Conclusion: The pre-operative nutritional status of patients with GC or CRC has an impact on post-operative infection occurrence. NRS2002 ≥5 was a risk factor for post-operative infection in patients with GC, and the PG-SGA B/C was a predictor of infections in patients with CRC.

Effect of Early vs Late Supplemental Parenteral Nutrition in Patients Undergoing Abdominal Surgery: A Randomized Clinical Trial.

Importance: The effect of and optimal timing for initiating supplemental parenteral nutrition (SPN) remain unclear after major abdominal surgery for patients in whom energy targets cannot be met by enteral nutrition (EN) alone. Objective: To examine the effect of early supplemental parenteral nutrition (E-SPN) (day 3 after surgery) or late supplemental parenteral nutrition (L-SPN) (day 8 after surgery) on the incidence of nosocomial infections in patients undergoing major abdominal surgery who are at high nutritional risk and have poor tolerance to EN. Design, Setting, and Participants: A multicenter randomized clinical trial was conducted from April 1, 2017, to December 31, 2018, in the general surgery department of 11 tertiary hospitals in China. Participants were those undergoing major abdominal surgery with high nutritional risk and poor tolerance to EN (≤30% of energy targets from EN on postoperative day 2, calculated as 25 and 30 kcal/kg of ideal body weight daily for women and men, respectively) and an expected postoperative hospital stay longer than 7 days. Data analysis was performed from February 1 to October 31, 2020. Interventions: Random allocation to E-SPN (starting on day 3 after surgery) or L-SPN (starting on day 8 after surgery). Main Outcomes and Measures: The primary outcome was the incidence of nosocomial infections between postoperative day 3 and hospital discharge. Results: A total of 230 patients (mean [SD] age, 60.1 [11.2] years; 140 men [61.1%]; all patients were of Han race and Asian ethnicity) were randomized (115 to the E-SPN group and 115 to the L-SPN group). One patient in the L-SPN group withdrew informed consent before the intervention. The E-SPN group received more mean (SD) energy delivery between days 3 and 7 compared with the L-SPN group (26.5 [7.4] vs 15.1 [4.8] kcal/kg daily; P < .001). The E-SPN group had significantly fewer nosocomial infections compared with the L-SPN group (10/115 [8.7%] vs 21/114 [18.4%]; risk difference, 9.7%; 95% CI, 0.9%-18.5%; P = .04). No significant differences were found between the E-SPN group and the L-SPN group in the mean (SD) number of noninfectious complications (31/115 [27.0%] vs 38/114 [33.3%]; risk difference, 6.4%; 95% CI, -5.5% to 18.2%; P = .32), total adverse events (75/115 [65.2%] vs 82/114 [71.9%]; risk difference, 6.7%; 95% CI, -5.3% to 18.7%; P = .32), and rates of other secondary outcomes. A significant difference was found in the mean (SD) number of therapeutic antibiotic days between the E-SPN group and the L-SPN group (6.0 [0.8] vs 7.0 [1.1] days; mean difference, 1.0 days; 95% CI, 0.2-1.9 days; P = .01). Conclusion and Relevance: In this randomized clinical trial, E-SPN was associated with reduced nosocomial infections in patients undergoing abdominal surgery and seems to be a favorable strategy for patients with high nutritional risk and poor tolerance to EN after major abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03115957.

Immediate vs. gradual advancement to goal of enteral nutrition after elective abdominal surgery: A multicenter non-inferiority randomized trial.

BACKGROUND & AIMS: The strategy of increasing the postoperative enteral nutrition dose to the target goal has not yet been clarified. This study aimed to determine whether an immediate goal-dose enteral nutrition (IGEN) strategy is non-inferior to a gradual goal-dose enteral nutrition (GGEN) strategy in reducing infections in patients undergoing abdominal surgery involving the organs of the digestive system. METHODS: This randomized controlled trial enrolled postoperative patients with nutritional risk screening 2002 scores ≥3 from 11 Chinese hospitals. Energy targets were calculated as 25 kcal/kg and 30 kcal/kg of ideal body weight for women and men, respectively. Patients were randomly assigned 1:1 to IGEN or GGEN group after enteral tolerance was confirmed (30% of the target on day 2). The IGEN group immediately started receiving 100% of the caloric requirements on day 3, while the GGEN group received 40% progressing to 80% of target on day 7. The primary endpoint was the infection rate until discharge, based on the intention-to-treat population. RESULTS: A total of 411 patients were enrolled and randomized to the IGEN and GGEN groups, and five patients did not receive the allocated intervention. A total of 406 patients were included in the primary analysis, with 199 and 207 in the IGEN and GGEN groups, respectively. Infection was observed in 17/199 (8.5%) in the IGEN group and 19/207 (9.2%) in the GGEN group, respectively (difference, -0.6%; [95% confidence interval (CI), -6.2%-4.9%]; P = 0.009 for non-inferiority test). There were significantly more gastrointestinal intolerance events with IGEN than with GGEN (58/199 [29.1%] vs. 32/207 [15.5%], P < 0.001). All other secondary endpoints were non-significant. CONCLUSIONS: Among postoperative patients at nutritional risk, IGEN was non-inferior to GGEN in regards to infectious complications. IGEN was associated with more gastrointestinal intolerance events. It showed that IGEN cannot be considered to be clinically directive. ClinicalTrials.gov (#NCT03117348).

α-E-Catenin (CTNNA1) Inhibits Cell Proliferation, Invasion and EMT of Bladder Cancer.

AIM: Bladder cancer (BLCA) is an urogenital system tumor with a high morbidity. We aimed to explore the function and potential mechanism of α-E-catenin (CTNNA1) in BLCA. METHODS: The CTNNA1 expression in BLCA tissues was detected using qRT-PCR and immunohistochemistry. QRT-PCR and Western blot were performed to measure the CTNNA1 expression in BLCA cell lines. CTNNA1 expression was up-regulated in T24 and UMUC-2 cells by CTNNA1 overexpression plasmid transfection. Cell proliferation, apoptosis, migration and invasion were respectively assessed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. The expression levels of epithelial-mesenchymal transition (EMT)-related factors were tested by qRT-PCR and Western blot. BLCA nude mice models were constructed to explore the effects of CTNNA1 on BLCA in vivo. Gene set enrichment analysis (GSEA) was proceeded to identify the CTNNA1-related pathways in BLCA. RESULTS: The expressions of CTNNA1 were down-regulated in BLCA tissues and cell lines, and its low expression indicated poor prognosis of BLCA patients. CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA cells. CTNNA1 enhanced E-cadherin expression and suppressed N-cadherin, snail, MMP2 and MMP9 expressions in BLCA cells, which suggested that CTNNA1 repressed EMT in BLCA cells. Moreover, CTNNA1 could inhibit tumor growth in vivo. CTNNA1 was positively associated with P53 and apoptosis pathways in BLCA cells. CONCLUSION: CTNNA1 inhibited cell proliferation, migration, invasion and EMT and promoted cell apoptosis in BLCA via activating P53 and apoptosis pathways. CTNNA1 might be a novel target in BLCA therapy.

RETRACTED: Methyltransferase-like 1 (METTL1) served as a tumor suppressor in colon cancer by activating 7-methyguanosine (m7G) regulated let-7e miRNA/HMGA2 axis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concern was raised by a reader that the pictures of different cell lines in Fig. 3A and Fig. 4D were from the same cell line, suggesting repeated use of the same picture. The editor contacted the corresponding author for explanation, but there was no reply. Apologies are offered to readers of the journal that this was not detected during the submission process.

MicroRNA-335 targets the MEK/ERK pathway to regulate the proliferation and metastasis of colon cancer.

Several studies have proved the tumor-suppressive effects of miR-335 but its role in colon cancer via regulation of the Raf/MEK/ERK signalling pathway is yet unknown. As such the main motive of conducting the present study was to elucidate the role of miR-335 in colon cancer via regulation of Raf/MEK/ERK signalling pathway and to explore its therapeutic potential. The results revealed significant (P < 0.05) downregulation of miR-335 in colon cancer and its overexpression led to a significant (P < 0.05) decline in viability of the HT-29 and SW948 cells. The TUNNEL assay showed miR-335 promotes apoptosis in the HT-29 and SW948 colon cancer cells and is also associated with increase in Bax and decrease in Bcl-2 expression. The results also revealed that miR-335 overexpression enhances the sensitivity of the HT-29 and SW948 cells to the apoptotic effects of cisplatin. From the transwell assays, it was found that the migration of the HT-29 and SW948 cells was decreased by 53% and 45% and while as invasion was decreased by 49% and 42% respectively (P < 0.05). Finally, western blot analysis showed that miR-335 blocks the Raf/MEK/ERK signalling pathway in HT-29 colon cancer cells. The results of in vivo study showed that miR-335 also exhibits tumor-suppressive effects on xenografted tumors. Taken together, it is concluded that miR-335 acts as tumor-suppressor in colon cancer and may exhibit therapeutic implications in its treatment.

Overexpressed methyltransferase-like 1 (METTL1) increased chemosensitivity of colon cancer cells to cisplatin by regulating miR-149-3p/S100A4/p53 axis.

Methyltransferase-like 1 (METTL1) mediated 7-methylguanosine (m7G) is crucial for the regulation of chemoresistance in cancer treatment. However, the role of METTL1 in regulating chemoresistance of colon cancer (CC) cells to cisplatin is still unclear. This study established the cisplatin-resistant CC (CR-CC) cells and found that METTL1 was low-expressed in CR-CC cells compared to their paired cisplatin-sensitive CC (CS-CC) cells. Besides, overexpressed METTL1 enhanced the cytotoxic effects of cisplatin on CR-CC cells. In addition, miR-149-3p was the downstream target of METTL1, which could be positively regulated by METTL1. Further results validated that miR-149-3p was low-expressed in CR-CC cells comparing to the CS-CC cells. In addition, the promoting effects of overexpressed METTL1 on cisplatin induced CR-CC cell death were abrogated by synergistically knocking down miR-149-3p. Furthermore, S100A4/p53 axis was the downstream target of METTL1 and miR-149-3p, and either overexpressed METTL1 or miR-149-3p increased p53 protein levels in CR-CC cells, which were reversed by upregulating S100A4. Similarly, the promoting effects of overexpressed METTL1 on cisplatin-induced CR-CC cell death were abrogated by overexpressing S100A4. Taken together, overexpression of METTL1 sensitized CR-CC cells to cisplatin by modulating miR-149-3p/S100A4/p53 axis.

Tumor-suppressor microRNA-139-5p restrains bladder cancer cell line ECV-304 properties via targeting Connexin 43.

BACKGROUND: In our previous paper, we demonstrated that Connexin 43 (CX43) was highly expressed in bladder cancer (BC) tissues. But the molecular mechanism about microRNAs (miRNAs) regulation upstream of CX43 in BC has not been well elucidated and remains to be further studied. MicroRNA-139-5p (miR-139-5p) is a tumor suppressor in progression of multifarious cancers including BC. Nevertheless, the underlying mechanisms of CX43/miR-139-5p in tumorigenesis of BC are still not well illustrated. The specific objective of our study was to inquiry the effect of CX43/miR-139-5p on BC progression and its underlying mechanism. METHODS: The bioinformatics analysis softwares were applied to predict the miRNAs in the upstream of CX43. First, the expression levels of miR-139-5p in BC tissues (tumor) and paracancer tissues (normal) were investigated using the data from The Cancer Genome Atlas database. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of miR-139-5p in three human BC cell lines 5637, T24, ECV-304 and a human bladder epithelial immortalized cell line SV-HUC-1 (normal control). Then si-CX43, si-control, miR-139-5p mimic, and its negative control (NC) were transfected into BC cell line ECV-304. The relationship of miR-139-5p and CX43 was analyzed by dual-luciferase reporter assay. The qRT-PCR and Western blotting were used to test the mRNA and protein expression level of CX43. The proliferation of ECV-304 and T24 cells were examined by cell counting kit-8. The migration and invasion of ECV-304 cells were tested by transwell assay. To determine whether miR-139-5p would affect cell proliferation, migration and invasion by targeting CX43, we executed the rescue assay. The comparison between two groups was analyzed by Student's t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test. RESULTS: The expression of miR-139-5p was remarkably down-regulated in BC tissues (tumor vs. normal, 2.286 ±â€Š0.017 vs. 3.211 ±â€Š0.034, t = 11.540, P < 0.0001) and cell lines (P < 0.01 in all BC cell lines). Besides, we also indicated that over-expression of miR-139-5p reduced the proliferation of ECV-304 (P = 0.001) and T24 cells (P = 0.005). Moreover, miR-139-5p over-expression weakened the invasion (P = 0.001) and migration (P = 0.001) of ECV-304 cells. Furthermore, the relative luciferase activity of CX43-wild type construct was distinctly lessened by up-regulation of miR-139-5p (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.916 ±â€Š0.063 vs. 0.356 ±â€Š0.048, t = 7.085, P = 0.002), nevertheless the activity of CX43-mutant type construct was untouched (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.918 ±â€Š0.057 vs. 0.878 ±â€Š0.039, t = 0.577, P = 0.595). Finally, the rescue assay revealed that CX43 deletion enhanced the depressor effect of miR-139-5p on ECV-304 cell proliferation (P < 0.01), invasion (P = 0.028), and migration (P = 0.014). CONCLUSION: MiR-139-5p, as a tumor-suppressor, repressed cell proliferation, invasion, and migration in BC, which might be achieved by regulating CX43.

Bladder Cancer-Specific Nuclear Matrix Proteins-4 May Be a Potential Biomarker for Non-Muscle-Invasive Bladder Cancer Detection.

AIMS: Bladder cancer-specific nuclear matrix protein-4 (BLCA-4) is a protein expressed mainly in bladder cancer tissues. Therefore, the aim of this study was to investigate its assisting diagnostic potential in non-muscle-invasive bladder cancer (NMIBC). METHODS: Twenty patients with NMIBC, 20 with benign prostatic hyperplasia (BPH), and 20 normal controls were included in this study. Blood and urine samples were collected from all patients. Moreover, cancer foci and adjacent tissue samples were collected from NMIBC patients, and normal bladder tissue samples were collected from patients with BPH. A competitive enzyme-linked immunosorbent assay was used to determine the BLCA-4 level in serum and urine, and immunohistochemistry was used to examine BLCA-4 expression in bladder cancer, adjacent, and normal tissues. RESULTS: Median urinary BLCA-4 levels in the NMIBC, BPH, and normal control groups were 0.759 ng/mL, 0.309 ng/mL, and 0.171 ng/mL, respectively. Urinary BLCA-4 level was significantly higher in the NMIBC group than in the other 2 groups (P < 0.01); meanwhile, the BPH group was higher than the normal control group (P < 0.05). Median serum BLCA-4 levels in the NMIBC, BPH, and normal control groups were 5.680 ng/mL, 5.928 ng/mL, and 5.473 ng/mL, respectively, showing no significant difference among groups (P > 0.05). CONCLUSION: As a new marker of bladder cancer, urinary BLCA-4 level detection might apply for clinical diagnosis or postoperative monitoring for NMIBC.

Clinical Significance of Serological and Urological Levels of Bladder Cancer-Specific Antigen-1 (BLCA-1) in Bladder Cancer.

BACKGROUND The aim of this study was to determine the clinical significance of the expression levels of bladder cancer-specific antigen-1 (BLCA-1) in the diagnosis of bladder cancer (BC). The study also determined the relationship between BLCA-1 expression levels and the clinical manifestation of BC. MATERIAL AND METHODS Patient samples were derived from 66 cases of BC that presented at the Department of Urology, Affiliated Hospital of Chengde Medical University, were recruited from April 2014 to May 2015, and 64 healthy control cases. Serum and urine BLCA-1 levels were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS Urine BLCA-1 levels in BC patients were significantly higher than that found in healthy controls (P<0.01). BLCA-1 levels in the urine of patients without mucus membrane invasion (Ta) were significantly different from urine levels found in patients with mucus membrane invasion (T1-T4; P=0.022). BLCA-1 levels in the serum of patients without muscular coat invasion (Ta-T1) were significantly different than serum levels of patients with muscular coat invasion (T2-T4; P=0.042). CONCLUSIONS BLCA-1 is involved in the appearance and development of BC. Clinical detection of serum and urine BLCA-1 protein levels showed a high level of sensitivity and specificity in diagnosing BC. Further study of the functional expression of BLCA-1 levels as a valuable and novel diagnostic marker in BC is clearly warranted.

Methylation Status of Transcriptional Modulatory Genes Associated with Colorectal Cancer in Northeast China.

BACKGROUND/AIMS: Methylation status plays a causal role in carcinogenesis in targeted tissues. However, the relationship between the DNA methylation status of multiple genes in blood leukocytes and colorectal cancer (CRC) susceptibility as well as interactions between dietary factors and CRC risks are unclear. METHODS: We performed a case-control study with 466 CRC patients and 507 cancer-free controls to investigate the association among the methylation status of individual genes, multiple CpG site methylation (MCSM), multiple CpG site heterogeneous methylation and CRC susceptibility. Peripheral blood DNA methylation levels were detected by performing methylation-sensitive high-resolution melting. RESULTS: Total heterogeneous methylation of CA10 and WT1 conferred a significantly higher risk of CRC (adjusted odds ratio [ORadjusted], 5.445; 95% confidence interval [CI], 3.075 to 9.643; ORadjusted, 1.831; 95% CI, 1.100 to 3.047; respectively). Subjects with high-level MCSM (MCSM-H) status demonstrated a higher risk of CRC (ORadjusted, 4.318; 95% CI, 1.529 to 12.197). Additionally, interactions between the high-level intake of fruit and CRH, WT1, and MCSM on CRC were statistically significant. CONCLUSIONS: The gene methylation status of blood leukocytes may be associated with CRC risk. MCSM-H of blood leukocytes was associated with CRC, especially in younger people. Some dietary factors may affect hypermethylation status and influence susceptibility to CRC.

Upregulation of miR-542-3p inhibits the growth and invasion of human colon cancer cells through PI3K/AKT/survivin signaling.

The present study was designed to assess the expression of microRNA-542-3p (miR-542-3p) in human colon cancer and investigate the possible molecular mechanisms underlying the effect of miR-542-3p on the growth and invasion of colon cancer cells. We found that miR-542-3p expression was downregulated in colon cancer patient tissues, compared with that observed in the control group. Silencing of miR­542-3p expression significantly promoted cell viability and inhibited apoptosis. In addition, overexpression of miR-542-3p significantly reduced cell viability and promoted apoptosis in colon cancer cells. Meanwhile, silencing of miR-542-3p expression significantly suppressed PI3K and p-AKT and survivin protein expression, while overexpression of miR-542-3p significantly induced PI3K and p-AKT and survivin protein expression in colon cancer cells. PI3K inhibitor (LY294002) or survivin inhibitor (YM155) suppressed PI3K/AKT/survivin signaling and increased the anticancer effects of miR-542-3p on the apoptosis in colon cancer. The present study demonstrated that upregulation of miR-542-3p inhibited the growth and invasion of colon cancer cells through PI3K/AKT/survivin signaling, highlighting a novel therapeutic approach for the treatment of colon cancer.

Dietary factors and polymorphisms in vitamin D metabolism genes: the risk and prognosis of colorectal cancer in northeast China.

CYP24A1 and CYP27B1 are critical genes determining 1α,25(OH)2D3 concentration and impacting on carcinogenesis. A case-control study including 528 colorectal cancer (CRC) patients and 605 cancer-free controls and a follow-up study with 317 cases were conducted in northeast China. Genotypes were tested by TaqMan Genotyping Assays. Individuals carrying the GG genotype of CYP27B1 G > T (rs10877012) exhibited decreased CRC risk compared with those with the TT genotype (ORadjusted (ORadj) = 0.57, 95% Confidence Interval (CI) = 0.38-0.84). Compared with the TT genotype, a significant association between the CC genotype of CYP27B1 C > T (rs4646536) and a reduced risk of CRC was observed (ORadj = 0.59, 95% CI = 0.40-0.88). We also observed significant combined effects of the two polymorphisms in CYP27B1 with dietary factors, including the intake of cereals, overnight meal, allium vegetables, pork, canned fruit, and braised fish, on CRC risk. These associations remained significant after Bonferroni correction for multiple comparisons. The Hazard Ration (HR) of patients with the AA genotype (CYP24A1 A > G, rs4809957) was 2.38 (95% CI = 1.30-4.37) when compared with the GG genotype. Thus, our findings suggested that two polymorphisms in CYP27B1 are associated with CRC susceptibility. CYP24A1 A > G (rs4809957) polymorphism may lead to a worse prognosis of CRC.

Bio-synthesis of peppermint leaf extract polyphenols capped nano-platinum and their in-vitro cytotoxicity towards colon cancer cell lines (HCT 116).

Bio-synthesis of Platinum nanoparticles (Pt NPs) was achieved using Mentha piperita (Peppermint) aqueous leaf extract. Further the ecofriendly synthesized Pt NPs were subjected for various characterization techniques. The characterization results inferred that the green synthesized Pt NPs were said to be in average particle size of 54.3nm. The particles are in spherical shape and it has been entrapped with secondary metabolites (Polyphenols). The polyphenols capped Pt NPs were screened for cytotoxicity against human colon cancer cell line (HCT 116). The results inferred that the ecofriendly synthesized Pt NPs decrease the viability of cancer cells at lower concentrations with IC50 value of 20µg/mL.