The clinical significance of mitochondrial calcium uniporter in gastric cancer patients and its preliminary exploration of the impact on mitochondrial function and metabolism.

Objective: The objective of this study is to elucidate the influence of MCU on the clinical pathological features of GC patients, to investigate the function and mechanism of the mitochondrial calcium uptake transporter MCU in the initiation and progression of GC, and to explore its impact on the metabolic pathways and biosynthesis of mitochondria. The ultimate goal is to identify novel targets and strategies for the clinical management of GC patients. Methods: Tumor and adjacent tissue specimens were obtained from 205 patients with gastric cancer, and immunohistochemical tests were performed to assess the expression of MCU and its correlation with clinical pathological characteristics and prognosis. Data from TCGA, GTEx and GEO databases were retrieved for gastric cancer patients, and bioinformatics analysis was utilized to investigate the association between MCU expression and clinical pathological features. Furthermore, we conducted an in-depth analysis of the role of MCU in GC patients. We investigated the correlation between MCU expression in GC and its impact on mitochondrial function, metabolism, biosynthesis, and immune cells. Additionally, we studied the proteins or molecules that interact with MCU. Results: Our research revealed high expression of MCU in the GC tissues. This high expression was associated with poorer T and N staging, and indicated a worse disease-free survival period. MCU expression was positively correlated with mitochondrial function, mitochondrial metabolism, nucleotide, amino acid, and fatty acid synthesis metabolism, and negatively correlated with nicotinate and nicotinamide metabolism. Furthermore, the MCU also regulates the function of the mitochondrial oxidative respiratory chain. The MCU influences the immune cells of GC patients and regulates ROS generation, cell proliferation, apoptosis, and resistance to platinum-based drugs in gastric cancer cells. Conclusion: High expression of MCU in GC indicates poorer clinical outcomes. The expression of the MCU are affected through impacts the function of mitochondria, energy metabolism, and cellular biosynthesis in gastric cancer cells, thereby influencing the growth and metastasis of gastric cancer cells. Therefore, the mitochondrial changes regulated by MCU could be a new focus for research and treatment of GC.

High-power tunable Raman soliton generation in large core diameter passive fibers via a precise fundamental-mode matching technique.

We demonstrate tunable high-power, high-energy Raman solitons with the range of 1.9-2.3 µm in large mode area (LMA) fibers and an optimized fundamental-mode matching technique for coupling LMA silica fibers. Finally, we obtained Raman solitons with a maximum output power of 5.8 W and a maximum pulse energy of 105 nJ in a LMA passive fiber with 32 µm core diameter, the tuning range of Raman soliton is 1.96-2.35 µm. In addition, we obtained Raman solitons with a maximum output power of 7.3 W and a maximum pulse energy of 126 nJ in a LMA passive fiber with 48 µm core diameter, the tuning range of Raman soliton is 1.96-2.27 µm. The output power of 7.3 W is the highest Raman soliton power currently available in silica fibers, and the result fills a gap in the generation of both high-power and high-energy Raman solitons in a LMA silica fiber.

Stabilizing Low-Valence Single Atoms by Constructing Metalloid Tungsten Carbide Supports for Efficient Hydrogen Oxidation and Evolution.

Designing novel single-atom catalysts (SACs) supports to modulate the electronic structure is crucial to optimize the catalytic activity, but rather challenging. Herein, a general strategy is proposed to utilize the metalloid properties of supports to trap and stabilize single-atoms with low-valence states. A series of single-atoms supported on the surface of tungsten carbide (M-WCx , M=Ru, Ir, Pd) are rationally developed through a facile pyrolysis method. Benefiting from the metalloid properties of WCx , the single-atoms exhibit weak coordination with surface W and C atoms, resulting in the formation of low-valence active centers similar to metals. The unique metal-metal interaction effectively stabilizes the low-valence single atoms on the WCx surface and improves the electronic orbital energy level distribution of the active sites. As expected, the representative Ru-WCx exhibits superior mass activities of 7.84 and 62.52 A mgRu -1 for the hydrogen oxidation and evolution reactions (HOR/HER), respectively. In-depth mechanistic analysis demonstrates that an ideal dual-sites cooperative mechanism achieves a suitable adsorption balance of Had and OHad , resulting in an energetically favorable Volmer step. This work offers new guidance for the precise construction of highly active SACs.

Laparoscopic versus Open Inguinal Hernia Repair in Aging Patients: A Propensity Score Matching-Based Retrospective Study.

Objective: Although laparoscopic repair has been widely carried out and promoted due to its minimally invasive advantages, open surgery is still popular compared to elderly patients. This study aims to compare the outcomes of laparoscopic (LIHR) vs open repair of inguinal hernias (OIHR) in elderly patients. Methods: A retrospective analysis of the database was performed to identify elderly patients, from January 2021 through December 2022, who underwent surgery for an inguinal hernia. After a 1:1 propensity score matching (PSM) with a caliper of 0.1 was conducted to balance potential bias, binary logistic regressions were used for categorical and continuous outcomes. Results: After PSM, 78 pairs of elderly patients were enrolled in this study, and there were no significant differences in baseline between LIHR and OIHR groups. Compared to OIHR, univariable and multivariable logistic regression analysis showed that LIHR was independently affected for reducing intraoperative hemorrhage (OR = 0.06, 95% CI: 0.02-0.18, P < 0.001) and shortening postoperative hospitalization time (OR = 0.29, 95% CI: 0.15-0.57, P < 0.001) in elderly patients. Furthermore, LIHR (OR = 0.28, 95% CI: 0.14-0.57, P < 0.001) and age (OR = 0.89, 95% CI: 0.82-0.96, P = 0.002) were independent affecting factors for relieving postoperative pain. Meanwhile, no obvious differences were detected in postoperative complications [LIHR 7.7% (6/78) vs OIHR 14.1% (11/78), P = 0.199]. Conclusion: LIHR was closely associated with reducing intraoperative hemorrhage and shortening postoperative hospitalization time. Whilst LIHR and age were independently affecting factors for relieving postoperative pain.

A Retrospective Study on the Three-Port Technique of Laparoscopic Common Bile Duct Exploration for the Management of Cholelithiasis and Choledocholithiasis.

Background: Laparoscopic cholecystectomy (LC) with laparoscopic common bile duct exploration (LCBDE) is convenient in treating cholelithiasis and choledocholithiasis due to its advantage of accelerated recovery. This retrospective study aimed to summarize the experience of cholelithiasis and choledocholithiasis treatment via three-port approach of LCBDE in Eastern China. Methods: Patients diagnosed with cholelithiasis and choledocholithiasis between July 2019 and October 2021 were included. Patients who received LC+LCBDE+primary suturing of the common bile duct (CBD) via a three-port approach were assigned to the LCBDE-P group, and those who received LC+LCBDE+T-tube drainage of CBD comprised the LCBDE-T group. The measurement data were compared between the two groups. P-values <0.05 indicated statistical significance. Results: A total of 88 patients were divided into two groups: LCBDE-P (n=50) and LCBDE-T (n=38). Multiple logistic regression analysis showed that LCBDE-P is associated with a shorter length of stay (OR=0.115, 95% CI: 0.040-0.329, P<0.001) and lower hospitalization costs (OR=0.120, 95% CI: 0.041-0.357, P<0.001). No significant differences between the two groups were detected in the operation time, intraoperative hemorrhage, clearance rate of CBD stones, postoperative liver function, and postoperative complications (P>0.05). Conclusion: The three-port approach of LCBDE is a safe and feasible strategy for managing cholelithiasis and choledocholithiasis. Compared to LCBDE-T, LCBDE-P reduces the length of hospital stay and medical costs during hospitalization.

The impact of laparoscopic versus open inguinal hernia repair for inguinal hernia treatment: A retrospective cohort study.

Objectives: Although laparoscopic inguinal hernia repair (LIHR) has been widely accepted for treating inguinal hernia, the procedure remains very technical and challenging. The present study aimed to assess the effect of LIHR in relation to operation time, intraoperative hemorrhage and postoperative hospitalization. Methods: A total of 503 patients with inguinal hernia admitted at the Wuxi Rehabilitation Hospital between June 2019 and July 2021 were included in this retrospective cohort study. Binary logistic and linear regressions were used for categorical and continuous outcomes, respectively. The learning curve was drawn by cumulative sum analysis. Results: Multivariate logistic regression analysis identified LIHR as an independent factor associated with prolonging operation time (odd ratio [OR] = 1.750, 95% confidence interval [CI]: 1.215-2.520, p = 0.003) and decreasing intraoperative hemorrhage levels (OR = 0.079, 95 CI: 0.044-0.142, p < 0.001). Multivariate linear regression identified LIHR (Coefficient = -0.702, 95% CI: [-1.050] to [-0.354], p < 0.001) as an independent factor for shortening postoperative hospitalization time. After learning curve, LIHR (OR = 1.409, 95% CI: 0.948 to 2.094, p = 0.090) no longer resulted as a risk factor prolonging operation time. Conclusions: LIHR is an important independent predictive factor for decreasing intraoperative hemorrhage levels and shortening postoperative hospitalization time. Additionally, LIHR does not prolong operation time after the learning curve.

Engineering Amorphous-Crystallized Interface of ZrNx Barriers for Stable Inverted Perovskite Solar Cells.

It is challenging to achieve long-term stability of perovskite solar cells due to the corrosion and diffusion of metal electrodes. Integration of compact barriers into devices has been recognized as an effective strategy to protect the perovskite absorber and electrode. However, the difficulty is to construct a thin layer of a few nanometers that can delay ion migration and impede chemical reactions simultaneously, in which the delicate microstructure design of a stable material plays an important role. Herein, ZrNx barrier films with high amorphization are introduced in p-i-n perovskite solar cells. To quantify the amorphous-crystalline (a-c) density, pattern recognition techniques are employed. It is found the decreasing a-c interface in an amorphous film leads to dense atom arrangement and uniform distribution of chemical potential, which retards the interdiffusion at the interface between ions and metal atoms and protect the electrodes from corrosion. The resultant solar cells exhibit improved operational stability, which retains 88% of initial efficiency after continuous maximum power point tracking under 1-Sun illumination at room temperature (25 °C) for 1500 h.

Postoperative complications and short-term prognosis of laparoscopic pancreaticoduodenectomy vs. open pancreaticoduodenectomy for treating pancreatic ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: Although laparoscopic pancreaticoduodenectomy (LPD) has been accepted worldwide for treating pancreatic ductal adenocarcinoma (PDA), it is a very technical and challenging procedure. Also, it is unclear whether LPD is superior to open pancreaticoduodenectomy (OPD). This study summarized the experience and efficacy of LPD for treating PDA in our medical center. METHODS: This retrospective cohort study included patients with PDA admitted at the Affiliated Hospital of Jiangnan University from October 2019 and January 2021. Patients received either LPD or OPD. Clinical outcomes (operation time, duration of anesthesia, intraoperative hemorrhage), postoperative complications, and short-term outcomes were compared. Cox proportional hazard model and Kaplan-Meier method were used to analyze overall survival (OS) and progression-free survival (PFS). RESULTS: Among the PDA patients, 101 patients underwent surgical treatment, 4 patients converted from LPD to OPD, and 7 of them received conservative treatment. Forty-six patients were cured of LPD, and 1 of them died shortly after the operation. Moreover, 44 patients received OPD, and there were 2 postoperative deaths. There were significant differences in the location of the operation time, duration of anesthesia, postoperative hemorrhage, abdominal infections, and postoperative pneumonia between the two groups (all p < 0.05). Multivariate analysis showed that LPD was an independent factor negatively correlated with the incidence of pneumonia (relative risk (RR) = 0.072, 95%CI: 0.016-0.326, p = 0.001) and abdominal infection (RR = 0.182, 95%CI: 0.047-0.709, p = 0.014). Also, there were no differences in OS (hazard ratio (HR) = 1.46, 95%CI: 0.60-3.53, p = 0.40) and PFS (HR = 1.46, 95%CI: 0.64-3.32, p = 0.37) at 12 months between the two groups. CONCLUSIONS: LPD could be efficacy and feasible for managing selected PDA patients. Also, LPD has a better effect in reducing postoperative pneumonia and abdominal infection compared to OPD.

Accident-related hepatic trauma in a medical clinical center in eastern China: a cross-sectional study.

BACKGROUND: The treatment of hepatic injury can be complex. Medical clinical centers are often the first line hospitals for the diagnosis and treatment of hepatic trauma in China. The aim of the study is to summarize the experience in the diagnosis and treatment of hepatic trauma in one medical clinical center in China. METHODS: This retrospective study included patients with hepatic trauma admitted between January 2002 and December 2019 at the Xishan People's Hospital of Wuxi. The outcomes were cure rate and death within 14 days post-discharge. RESULTS: Among the 318 patients with hepatic trauma, 146 patients underwent surgical treatment, and 172 received conservative treatment; three patients were transferred to other hospitals for further treatment; 283 patients were cured, and 35 died. Severe hepatic trauma occurred in 74 patients, with a mortality rate of 31.1% and accounting for 65.7% of total mortality. American Association for the Surgery of Trauma (AAST) grading ≥ III (OR = 3.51, 95%CI: 1.32-9.37, P = 0.012) and multiple organ injury (OR = 7.51, 95%CI: 2.51-22.46, P < 0.001) were independently associated with death. Among patients with AAST grading ≥ III, surgery was an independent protective factor for death (OR = 0.08, 95%CI: 0.01-0.45, P = 0.004). Among patients with ASST ≥ III and who underwent surgery, age (OR = 5.29, 95%CI: 1.37-20.33, P = 0.015) and peri-hepatic packing (PHP) (OR = 5.54, 95%CI: 1.43-21.487, P = 0.013) were independently associated with death. CONCLUSIONS: AAST grading ≥ III and multiple organ injury were independently associated with death. Among patients with AAST grading ≥ III, surgery was an independent protective factor for death. Among patients with ASST ≥ III and who underwent surgery, age and PHP were independently associated with death.

Efficacy of Standardized Rehabilitation in the Treatment of Diastasis Rectus Abdominis in Postpartum Women.

PURPOSE: The incidence of diastasis rectus abdominis (DRA) in parturients is continuously increasing, which may cause uncomfortable and affect the quality of life. The present study aims to retrospectively summarize the experience and efficacy in the treatment of DRA via standardized rehabilitation procedures in Eastern China. METHODS: This retrospective study included the parturients with DRA admitted to the Xishan People's Hospital of Wuxi between January 2017 and May 2021. Patients were separated into standardized rehabilitation group (SR) and non-standardized rehabilitation group (non-SR). The outcomes were the change in rectus abdominis separation and Physical Functioning Scale (PFS). Measurement data were compared between the two groups, and multivariate linear regression was used to analyze the factors associated with the standardized rehabilitation process. P values < 0.05 were considered statistically significant. RESULTS: Among a total of 294 patients with DRA who were included in the study, 171 patients were treated with SR (SR), and the other 123 patients were treated without SR process (non-SR). Compared with non-SR, the separation of the rectus abdominis was significantly reduced in SR after standardized rehabilitation treatment (p value < 0.0001). The multiple linear regression model analysis results suggested that standardized rehabilitation was an independent factor influencing the prognosis of DRA in parturients (p < 0.0001). In addition, the quality of life of the study group was significantly improved (p < 0.0001). CONCLUSION: Standardized rehabilitation method revealed high efficiency in treating DRA in postpartum women and could improve the quality of life of parturients.

ENST00000430471 Promotes Development and Metastasis of Colorectal Cancer by Regulating the Expression of YBX-1.

BACKGROUND INFORMATION: Colorectal cancer (CRC) is a common malignant tumor of the digestive system. Long non-coding (lnc) RNA ENST00000430471 has been reported to be involved in CRC development and metastasis because of its cancer-promoting ability. However, the detailed molecular mechanisms of ENST00000430471 in CRC remain largely unknown. METHODS: The cell proliferation assay and Xenograft experiment were performed to examine the proliferation rate of the tumor cells. Invasiveness and migration capability of the cells were evaluated using the invasion and wound healing assays, respectively. In addition, the RNA pull-down assay and subsequent mass spectrometry techniques were performed to identify the proteins interacting with ENST00000430471. RESULTS: Herein, small specific inhibiting (si) RNA-si0471#2 was used to silence ENST00000430471 in HCT116 and SW620 cell lines. This led to a significant reduction in cell proliferation, migration, and invasion. The RNA pull-down assay and mass spectrometry further revealed that ENST00000430471 interacted with several proteins such as the Y-box-binding protein 1 (YBX-1). On one hand, silencing of ENST00000430471 decreased the mRNA and protein expression levels of YBX-1. On the other hand, overexpression of YBX1 partially attenuated the suppression of cell proliferation, invasion, and migration induced by ENST00000430471 silencing. CONCLUSION: Silencing of ENST00000430471 inhibits proliferation, migration, and invasion of CRC cells by regulating YBX-1 expression. These results provide baseline information that is essential in the identification of effective therapeutic targets for CRC therapy.

Systematic assessment of complications after robotic-assisted total versus distal gastrectomy for advanced gastric cancer: A retrospective propensity score-matched study using Clavien-Dindo classification.

BACKGROUND: Despite increasing evidence demonstrated robot-assisted distal gastrectomy (RADG) is safe and feasible for the treatment of advanced gastric cancer (AGC), robot-assisted total gastrectomy (RATG) remains a challenging procedure due to its technical difficulties and possible postoperative complications (POCs). This study aimed to systematically evaluate POCs following RATG. METHODS: Between January 2017 and January 2019, 319 AGC patients with pathological stage T2-4aN0-3M0 who underwent RADG or RATG were enrolled. POCs were stratified using the Clavien-Dindo classification. One-to-one propensity score matching was performed to reduce confounding differences. RESULTS: After matching, 266 patients met the criteria for further analysis. Ultimately, 64 patients (24.1%) who developed POCs had 126 clinical manifestation events. Overall the POCs rate was significantly greater after RATG in comparison with RADG (29.3% vs. 18.8%; P = 0.045), and more major POCs (Clavien-Dindo grade ≥ IIIa) were observed in the RATG group (14.3% vs. 5.3%; P = 0.013). The POCs were then classified into local and systemic POCs. The rates of local POCs (35.3% vs. 19.5%; P = 0.004) and systemic POCs (24.8% vs. 15.0%; P = 0.046) were significantly higher in the RATG group than the RADG group. Subgroup analysis showed that the anastomotic leakage rate was higher after RATG (5.3% vs. 0.8%; P = 0.031), whereas the remaining POCs were similar between the two groups. Patients with higher POCs significantly had longer postoperative length of stay (R = 0.895, P = 0.003). Multivariate analysis confirmed age, extent of resection, and TNM stage were risk factors for all POCs. CONCLUSIONS: These findings demonstrated that RATG is technically feasible and safe for treatment of AGC with acceptable morbidity and mortality rates. The POCs rate of RATG was higher than RADG, especially for anastomotic leakage. More effective anastomotic techniques are needed in RATG to prevent leakage.

Long non-coding RNA CASC19 is associated with the progression and prognosis of advanced gastric cancer.

Evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) are involved in the development and progression of advanced gastric cancer (AGC). Using RNA sequencing data and clinical information obtained from The Cancer Gene Atlas, we combined differential lncRNA expression profiling and weighted gene co-expression network analysis to identify key lncRNAs associated with AGC progression and prognosis. Cancer susceptibility 19 (CASC19) was the top hub lncRNA among the lncRNAs included in the gene module most significantly correlated with AGC's pathological variables. CASC19 was upregulated in AGC clinical samples and was significantly associated with higher pathologic TNM stage, pathologic T stage, lymph node metastasis, and poor overall survival. Multivariable Cox analysis confirmed that CASC19 overexpression is an independent prognostic factor for overall survival. Furthermore, quantitative real-time PCR assay confirmed that CASC19 expression in four human gastric cancer cells (AGS, BGC-823, MGC-803, and HGC-27) was significantly upregulated compared with human normal gastric mucosal epithelial cell line (GES-1). Functionally, CASC19 knockdown inhibited GC cell proliferation and migration in vitro. These findings suggest that CASC19 may be a novel prognostic biomarker and a potential therapeutic target for AGC.

First-line application of apatinib combined with S-1 based on peripheral circulating tumor cell screening to treat advanced gastric adenocarcinoma: a case report.

Apatinib mesylate, a small-molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor-2 (VEGFR-2), has been recommended as a third-line class A agent for patients with advanced gastric adenocarcinoma in China since April 2018. Thus far, there is no case report on the combined use of apatinib and S-1 as the first-line treatment option for metastatic gastric cancer (GC) patients based on peripheral circulating tumor cell (pCTC) monitoring. We present a unique case in which liver metastases originating from GC gradually shrank and disappeared in the presence of pCTC-positive disease after treatment with apatinib for 17 months. More surprisingly, the pCTCs became negative after the addition of S-1 halfway through treatment. A 71-year-old Chinese man who underwent gastroscopic biopsy and laparoscopy was diagnosed with gastric adenocarcinoma with multiple liver metastases. The pathological stage was T4NxM1. The patient obtained clinical benefit from first-line apatinib within 4 weeks. After developing grade 2 hand-foot syndrome, the patient began to take S-1 alone. When the condition was significantly relieved, the elderly patient continued to take apatinib combined with S-1 and achieved satisfactory therapeutic results. Many studies suggest that the prognosis of this type of GC is grim. However, apatinib increased the overall survival (OS) duration of the patient to 34 months. We hypothesize that combining apatinib with S-1 as a first-line therapeutic option for pCTC-positive advanced GC is feasible.

A Competing Endogenous RNA Network Reveals Novel Potential lncRNA, miRNA, and mRNA Biomarkers in the Prognosis of Human Colon Adenocarcinoma.

BACKGROUND: Accumulating evidence indicated that long noncoding RNAs (lncRNAs) have a wide range of biological functions and may play significant roles in tumorigenesis and progression. However, the understanding of its functions and related competitive endogenous RNAs (ceRNAs) networks is much less than that of protein-coding genes, particularly in colon adenocarcinoma. METHODS: We comprehensively analyzed the sequencing data of protein-coding and noncoding RNAs in colon adenocarcinoma patients from The Cancer Genome Atlas (TCGA) database. Next, we constructed colon adenocarcinoma-specific ceRNA network and evaluated the effect of these RNAs on overall survival (OS) for colon adenocarcinoma patients. RESULTS: Totally, 1138 differentially expressed lncRNAs (DElncRNAs), 245 microRNAs (DEmiRNAs), and 2081 mRNAs (DEmRNAs) were identified using a threshold of |log2FoldChange| >2.0 and adjusted P-value < 0.01. Subsequently, a colon adenocarcinoma-specific ceRNA network was successfully established with133 DElncRNAs, 29 DEmiRNAs, and 55 DEmRNAs. Among ceRNA network, seven DElncRNAs (AL590483.1, AP004609.1, ARHGEF26-AS1, HOX transcript antisense RNA (HOTAIR), ITCH-IT1, KCNQ1OT1, and LINC00491), four DEmiRNAs (hsa-mir-143, hsa-mir-183, hsa-mir-216a, and hsa-mir-424), and six DEmRNAs (FJX1, TPM2, ULBP2, PDCD4, PLAU, and SERPINE1) significantly correlated with OS (all P-value < 0.05). Notably, several interactions were highlighted in the ceRNA network, such as "KCNQ1OT1-hsa-mir-183-PDCD4", "KCNQ1OT1-hsa-mir-424-TPM2", "HOTAIR-hsa-mir-143-SERPINE1", and "ARHGEF26-AS1-hsa-mir-143-SERPINE1". CONCLUSIONS: These findings reveal several molecules might be novel important prognostic factors and potential treatment targets for colon adenocarcinoma. In addition, these observations contribute to a more comprehensive understanding of lncRNA-related ceRNA network and provide novel strategies for subsequent functional studies of lncRNAs in colon adenocarcinoma.

Long non-coding RNA HOTTIP is able to predict poor prognosis in various neoplasms: A meta-analysis.

HOXA distal transcript antisense RNA (HOTTIP), a critical oncogenic long non-coding RNA, has been reported to be aberrantly regulated in various cancer types. The present meta-analysis aimed to investigate HOTTIP as a potential clinical applicable prognostic biomarker in malignant neoplasms. Literature collections were performed by searching the electronic databases, PubMed and Web of Science (up to July 20, 2016). All the relevant searches were conducted to identify the association of HOTTIP with the overall survival (OS) rate. A total of six articles consisting of 508 patients were included in the present meta-analysis. The results suggested that the overexpression of HOTTIP is closely correlated with poor OS (hazard ratio=2.28; 95% confidence interval=1.71-3.04; P=0.000). In conclusion, the present meta-analysis has demonstrated that an increased expression level of HOTTIP is correlated with poor OS in different types of cancer, suggesting that HOTTIP potentially serves as a reliable prognostic biomarker in different types of cancer.

Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO.

This study aimed to investigate the role of long noncoding RNAs (lncRNAs) in the metastasis of colorectal cancer (CRC). Metastasis is an important prognostic factor of CRC, and lncRNAs have been implicated in tumor proliferation and metastasis. The human CRC cell lines HCT116, HT29, SW480, DLD-1, and SW620 were used in the study. Genome-wide lncRNA expression patterns in metastatic lymph nodes compared with paired normal lymph nodes of CRC were assessed by microarray analysis. Gastric adenocarcinoma predictive long intergenic noncoding (GAPLINC) RNA was detected via functional prediction. The increased expression of GAPLINC was found to be positively correlated with larger tumor size, advanced tumor stage (T stage), advanced node stage (N stage), increased death, and shorter survival of patients with CRC by in situ hybridization analysis. Besides, the decreased expression of GAPLINC could significantly repress CRC cell invasion in vitro and also inhibit proliferation in vitro and in vivo. RNA pull-down with mass spectrum experiments revealed that PTB-associated splicing factor (PSF) and non-POU-domain-containing octamer-binding (NONO) protein bound to GAPLINC and reversed the effect of GAPLINC on cell invasion. Gene array and bioinformatics analyses identified that snail family zinc finger 2 (SNAI2) was involved in the biological processes of GAPLINC/PSF/NONO. This study indicated the importance of GAPLINC in promoting CRC invasion via binding to PSF/NONO and partly by stimulating the expression of SNAI2. Hence, GAPLINC may serve as a promising target for CRC diagnosis and therapy. The findings may help in developing a novel therapeutic strategy for patients with CRC.

Long noncoding RNA expression profile analysis of colorectal cancer and metastatic lymph node based on microarray data.

Long noncoding RNAs (lncRNAs) are emerging as an important part of biological progress in cancers, yet the aberrant lncRNAs implicated in colorectal cancer (CRC) with lymph node metastasis remain unknown. In this study, a total of 390 lncRNA transcripts and 508 mRNA transcripts were dysregulated in tumor tissues compared with paired metastatic lymph nodes. Functional prediction showed that lots of lncRNAs might be involved in biological pathways related to CRC metastasis by cis-regulation and trans-regulation of coexpressed genes. As a representative, ENST00000430471 was associated with cell proliferation and invasion of CRC cells. These results provided support for further investigations of the metastatic pathogenesis of CRC.

Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.

Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1ß in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1ß were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.

Long noncoding RNA expression patterns in lymph node metastasis in colorectal cancer by microarray.

AIM: To profile the long noncoding RNA (lncRNA) expression patterns in normal lymph node (NLN) of colorectal cancer compared with paired metastatic lymph node (MLN). MATERIALS AND METHODS: MLN, NLN lncRNA and messenger RNA (mRNA) expression levels were determined by microarray in three patients; quantitative reverse transcription-polymerase chain reaction validation of 3 differentially expressed lncRNAs was conducted in another 26 patients. The lncRNAs' functions were predicted through coexpressed mRNA annotations. RESULT(S): A total of 1133 lncRNA transcripts transcripts were dysregulated in metastatic lymph node, compared with normal lymph node. The expressions of the 3 chosen lncRNAs were validated by quantitative reverse transcription-polymerase chain reaction. Functional analysis suggests that several groups of lncRNAs may participate in biological pathways related to colorectal cancer by cis- and/or trans-regulation of protein-coding genes. CONCLUSION(S): This study constitutes the first report of lncRNA expression patterns in human MLN, NLN of colorectal cancer. More than 1000 dysregulated lncRNA transcripts are found by microarray.