The Role of Endoscopic Ultrasound-guided Fine-needle Aspiration of Pelvic Lesions: A Meta-analysis.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a potentially valuable tool for the diagnosis of pelvic lesions. The aim of this meta­analysis was to evaluate the efficacy and feasibility of EUS-FNA in the diagnosis of pelvic lesions. METHODS: We performed a computerized search of PubMed, EMBASE, Cochrane Library, and Science Citation Index, through March 2023. The main outcome measures examined in the meta-analysis were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. RESULTS: We evaluated 22 trials that used surgical pathology or imaging follow-up results as the reference standard. The studies comprised 844 patients. The cumulative sensitivity, specificity, PPV, NPV, and accuracy were 94%, 100%, 100%, 89%, and 96%, respectively. In the subgroup analysis, the prospective studies revealed the cumulative sensitivity, specificity, PPV, NPV, and accuracy were 91%, 100%, 100%, 85%, and 93%, respectively. CONCLUSIONS: In conclusion, we provide evidence that EUS-FNA is a qualitative diagnostic technique with high sensitivity, specificity, PPV, and accuracy. However, its NPV is slightly low, which does not exclude the risk of a missed diagnosis, and more randomized controlled trials or prospective studies are still needed in the future. EUS-FNA is effective and feasible for pelvic space-occupying lesions. This technique has high clinical application value for pelvic lesions.

An acceptability study of the introduction of total online or partial online PBL in a large classroom setting in biochemistry.

BACKGROUND: Traditional problem-based learning (PBL) relying on tutored learning in small groups is very resource-intensive. Little is known about the benefits of PBL in a large classroom setting. This paper introduced a PBL case into the traditional didactic biochemistry course and investigated the acceptability of total online or partial online PBL in a large classroom setting introduced during the coronavirus pandemic. METHODS: The students were allocated into either total online Group 1, partial online Group 2, or partial online and with poorer academic performance Group 3. A questionnaire comprising of 8 closed-ended questions and 2 open-ended questions and final exam performances were used to evaluate the acceptability of total online or partial online PBL in a large classroom setting. The 8 closed-ended questions were analysed by the Kruskal-Wallis test or chi-square tests. The word cloud analysis of the 2 open-ended questions were conducted by Wenjuanxing. Students' performances in the final examination were analysed by One-way Anova. RESULTS: Both total online and partial online PBL were rated highly by the students. Overall, there were no significant differences in the effectiveness evaluation of PBL between Group 2 and Group 3. There were no significant differences in final exam performances between Group 1 and Group 2. However, Group 1 rated the effectiveness of PBL much higher than Group 2 and 3. Word cloud analysis of the 2 open-ended questions showed students' positive perspectives of PBL. In biochemistry teaching, from the perspective of the students, the expected optimal number of useful PBL cases might be 2. CONCLUSIONS: Both total online and partial online PBL in a large classroom setting were widely accepted as a beneficial supplement to traditional biochemistry classes.

Single-Cell RNA Sequencing Reveals Roles of Fibroblasts During Intestinal Injury and Repair in Rats with Severe Acute Pancreatitis.

Purpose: To explore the molecular mechanisms of intestinal injury and treatment by analyzing changes in cellular heterogeneity and composition in rat ileal tissue during injury and treatment processes. Methods: We constructed a rat model of SAP and evaluated treatment with an injected of monoacylglycerol lipase (MAGL) inhibitor (JZL184) solution using three experimental groups: healthy male Sprague-Dawley (SD) rats injected with vehicle (CON), male SD SAP model rats injected with vehicle (SAP), and male SAP rats injected with JZL184. We obtained and prepared a single-cell suspension of ileal tissue of each rat for single-cell transcriptome sequencing. Results: This project classified changes in cellular heterogeneity and composition in rat ileal tissue during SAP-induced intestinal injury and MAGL treatment. We found that the number of fibroblast clusters was decreased in the SAP group relative to the CON group, and increased after JZL184 treatment. Further analysis of differences in gene expression between cell clusters in each group reveals that fibroblasts had the greatest number of differentially expressed genes. Most notably, expression of genes involved in communication between cells was found to vary during SAP-induced intestinal injury and JZL184 treatment. Among these changes, the degree of difference in expression of genes involved in communication between fibroblasts and other cells was the highest, indicating that fibroblasts in rat ileal tissue affect intestinal injury and repair through cell-to-cell communication. In addition, our results reveal that differentially expressed RNA-binding proteins in fibroblasts may affect their functions in intestinal injury and treatment by affecting the expression of genes regulating communication between cells. Conclusion: These findings emphasize the importance of understanding the interactions between fibroblasts and other cells in the context of intestinal injury, providing valuable insights for further exploring molecular mechanisms and insight for discovering new treatment targets and strategies.

Interleukin­22 alleviates arginine­induced pancreatic acinar cell injury via the regulation of intracellular vesicle transport system: Evidence from proteomic analysis.

Acute pancreatitis (AP) is a severe inflammatory condition characterized by the activation of pancreatic enzymes within acinar cells, leading to tissue damage and inflammation. Interleukin (IL)-22 is a potential therapeutic agent for AP owing to its anti-inflammatory properties and ability to promote tissue repair. The present study evaluated the differentially expressed proteins in arginine-induced pancreatic acinar cell injury following treatment with IL-22, and the possible mechanisms involved in IL-22-mediated alleviation of AP. AR42J cells were stimulated using L-arginine to establish an acinar cell injury model in vitro and the damaged cells were subsequently treated with IL-22. The characteristics of the model and the potential therapeutic effects of IL-22 were examined by CCK-8 assay, flow cytometry, TUNEL assay, transmission electron microscopy and ELISA. Differentially expressed proteins in cells induced by arginine and treated with IL-22 were assessed using liquid chromatography-mass spectrometry. The identified proteins were further subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis to elucidate their functional roles. The present study demonstrated that arginine-stimulated cells showed significant pathological changes resembling those in AP, which were alleviated after IL-22 treatment. Proteomic analysis then demonstrated that in IL-22-treated cells, proteins related to the formation and fusion of autophagosomes with lysosomes were significantly downregulated, whereas endocytosis related proteins were enriched in the upregulated proteins. After IL-22 treatment, western blotting demonstrated reduced expression of autophagy-associated proteins. In conclusion, by inhibiting the formation and fusion of autophagosomes with lysosomes, IL-22 may have mitigated premature trypsinogen activation, subsequently minimizing acinar cell injury induced by L-arginine. This was accompanied by concurrent upregulation of endocytosis, which serves a pivotal role in sustaining regular cellular material transport and signal propagation. This research underscored the potential of IL-22 in mitigating arginine-induced AR42J injury, which could be valuable in refining treatment strategies for AP.

Characterization of dynamical changes in vital signs during allogeneic human umbilical cord-derived mesenchymal stem cells infusion.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), a kind of adult stem cell, were studied for clinical applications in regenerative medicine. To date, the safety evaluations of intravenous infusion of allogeneic hUC-MSCs were focused on fever, infection, malignancy, and death. However, the characteristics of dynamical changes in vital signs during hUC-MSCs infusion are largely unknown. In this study, twenty participants with allogeneic hUC-MSCs transplanted (MSC group) and twenty sex- and age-matched individuals with cardiovascular disease who treated with the equal volume of 0.9% normal saline were recruited (NS group). Heart rate, respiratory rate, oxygen saturation, systolic and diastolic blood pressure, and temperature were monitored at intervals of 15 min during infusion. Adverse events were recorded during infusion and within seven days after infusion. No adverse events were observed during and after infusion in both groups. Compared with the baseline, the mean systolic blood pressure (SBP) levels were significantly decreased at 15 min, 30 min, 45 min and 60 min in the MSC group (all P < 0.05) during infusion. In addition, SBP changed significantly from baseline during hUC-MSCs infusion when compared with that of NS group (P < 0.05). Repeated measures analysis of variance confirmed difference over time on the SBP levels (P < 0.05). Our results showed that the process of allogeneic hUC-MSCs intravenous infusion was safe and the vital signs were stable, whereas a slight decrease in SBP was observed.

Effect of 3-Dimensional Imaging Device on Polyp and Adenoma Detection During Colonoscopy: A Randomized Controlled Trial.

INTRODUCTION: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy. METHODS: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat. RESULTS: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists. DISCUSSION: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000.

Long-term changes in corneal densitometry and associated factors following small incision lenticule extraction for moderate and high myopia.

Purpose: To investigate long-term trends in corneal densitometry and associated influencing factors following small incision lenticule extraction (SMILE). Methods: A comparative study was performed among 72 eyes of 38 patients undergoing SMILE. Eyes were divided into moderate myopia [mean spherical equivalent (SE),-4.22 ± 0.68D] and high myopia (mean SE,-7.63 ± 1.09 D) groups. Visual acuity, manifest refraction, corneal topography and corneal densitometry (CD) were evaluated preoperatively and 3 years postoperatively. Results: The efficacy indices at last postoperative follow-up (42.47 ± 0.51 months) were 0.92 ± 0.21 and 0.97 ± 0.22, the safety indices were 1.12 ± 0.17 and 1.14 ± 0.21 for high and moderate myopia, respectively (all P > 0.05). CD values in the 0-6 mm zone of the posterior corneal layer was statistically significantly lower than the preoperative values in both groups. Postoperative CD values (0-2 mm zone) in the posterior layer of the high myopia group were statistically significantly lower than in the moderate myopia group (P = 0.025); CD values (2-6 mm zone) in the anterior layer were higher in the high myopia group (P = 0.026). Correlation analyses showed that CD values in the 0-2 mm middle layer were negatively correlated with lenticule thickness in high myopia (r = -0.411, P = 0.016); there was a negative correlation between the CD values (0-6 mm) and corneal oblique trefoil in this group (P < 0.05). Conclusion: Corneal transparency in the 0-6 mm zone of the posterior cornea increased following SMILE in moderate and high myopia. Long-term CD values in high myopia may be correlated with oblique trefoil and lenticule thickness.

Corrigendum: Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis.

[This corrects the article DOI: 10.3389/fphar.2022.869482.].

Effect of Monoacylglycerol Lipase Inhibition on Intestinal Permeability of Rats With Severe Acute Pancreatitis.

Background: Endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid that is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). In this study, we investigated the effects of MAGL inhibition on intestinal permeability and explored the possible mechanism. Methods: A rat model of severe acute pancreatitis (SAP) was established. Rats were divided into three groups according to treatment. We analyzed intestinal permeability to fluorescein isothiocyanate-dextran and the levels of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and 2-AG. Hematoxylin and eosin staining was used to assess histological tissue changes. In vivo intestinal permeability was evaluated by transmission electron microscopy. We obtained ileum tissues, extracted total RNA, and applied RNA-sequencing. Sequencing data were analyzed by bioinformatics. Results: Inflammatory factor levels were higher, while 2-AG levels were lower in the SAP group compared with the control group. Administration of JZL184 to rats with SAP increased the levels of 2-AG and lowered the levels of IL-6 and TNF-α. Notably, intestinal permeability was improved by JZL184 as demonstrated by fluorescein isothiocyanate-dextran measurement, hematoxylin and eosin staining, and transmission electron microscopy. RNA-sequencing showed significant transcriptional differences in SAP and JZL184 groups compared with the control group. KEGG analysis showed that the up- or downregulated genes in multiple comparison groups were enriched in two pathways, focal adhesion and PI3K-Akt signaling pathways. Differential alternative splicing (AS) genes, such as Myo9b, Lsp1, and Git2, have major functions in intestinal diseases. A total of 132 RNA-binding proteins (RBPs) were screened by crossing the identified abnormally expressed genes with the reported RBP genes. Among them, HNRNPDL coexpressed the most AS events as the main RBP. Conclusion: MAGL inhibition improved intestinal mucosal barrier injury in SAP rats and induced a large number of differentially expressed genes and alternative splicing events. HNRNPDL might play an important role in improving intestinal mucosal barrier injury by affecting alternative splicing events.

Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial.

BACKGROUND AND AIM: Bowel preparation is an important determinant of the quality of colonoscopy. The traditional split-dose regimen of 4 L polyethylene glycol (PEG) solutions for bowel preparation is effective but poorly tolerated. The aim of this was to study the efficacy and tolerability of using linaclotide as an adjunctive agent with low-volume PEG for bowel preparation. METHODS: This was an endoscopist-blinded, randomized, controlled trial of 432 patients randomly assigned to three groups: 2 L PEG, 4 L PEG and 2 L PEG + 290 µg linaclotide (2 L PEG + L group). The primary outcome measure was efficacy of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), with secondary outcomes of patients' tolerance, defecating frequency, complications, sleeping quality, cecal intubation rate, preparation-to-colonoscopy interval, withdrawal time, cecal intubation time, and adenoma and polyp detection rates. RESULTS: The percentage of adequate bowel preparation in the 2 L PEG + L group was higher than that of the 2 L PEG group (87.9% vs. 77.0%; P = 0.017), but not the 4 L PEG group (87.9% vs. 91.4%; P = 0.339). In terms of the mean (SD) BBPS score for the total and segmental colons, the bowel cleansing efficacy of 2 L PEG + L was superior to that of 2 L PEG and similar to that of 4 L PEG. Patient's tolerance (including complications, willingness to repeat and sleeping quality) were compatible between the 2 L and 2 L + L group, and the 4 L group was the worst among these three groups. CONCLUSION: Two liters of PEG combined with 290 µg linaclotide was an effective and well-tolerated bowel preparation regimen.

Circ_ZFP644 attenuates caerulein-induced inflammatory injury in rat pancreatic acinar cells by modulating miR-106b/Pias3 axis.

(AP) is a kind of inflammatory misorder existing in pancreas. Non-coding RNAs (ncRNAs) have been reported to play important roles in development of AP. The current study was designed to explore the role of circular RNA zinc finger protein 644 (circRNA circ_ZFP644) in caerulein-induced AR42J cells. AP model in vitro was established by exposure of rat pancreatic acinar AR42J cells to caerulein. Amylase activity was measured using a kit. Enzyme-linked immunosorbent assay (ELISA) was performed to examine the levels of several inflammatory factors. The expression of circ_ZFP644, microRNA (miR)-106b and protein inhibitor of activated STAT 3 (Pias3) was detected by quantitative real-time PCR (qRT-PCR) or western blot assay. And flow cytometry was employed to monitor cell apoptosis. Western blot assay was also conducted to analyze the expression of apoptosis-related proteins. The association among circ_ZFP644, miR-106b and Pias3 was validated by dual-luciferase reporter assay. Caerulein treatment activated amylase activity and promoted the secretion of inflammatory cytokines in AR42J cells. Circ_ZFP644 and Pias3 were downregulated, but miR-106b was upregulated in caerulein-induced AR42J cells. Enforced expression of circ_ZFP644 or miR-106b inhibition could reduce amylase activity and inflammatory cytokine secretion, while promote apoptosis in caerulein-induced AR42J cells, which was almost reversed by Pias3 knockdown. Circ_ZFP644 targeted miR-106b to upregulate Pias3 expression. Circ_ZFP644 might exert its anti-inflammation and pro-apoptosis roles in caerulein-induced AR42J cells by regulating miR-106b/Pias3 axis.

Stylet Slow-pull Versus Standard Suction for Endoscopic Ultrasound-guided Fine-needle Aspiration/Biopsy of Pancreatic Solid Masses: A Meta-Analysis.

BACKGROUND AND STUDY AIM: There is limited evidence on the diagnostic performance of the stylet slow-pull (SP) method for endoscopic ultrasound-guided fine-needle aspiration/biopsy. The aim of this study was to compare the SP method with standard suction (SS) for endoscopic ultrasound-guided fine-needle aspiration/biopsy of solid pancreatic masses. METHODS: A computerized bibliographic search of the main databases, including PubMed, EMBASE, Cochrane Library, and Science Citation Index, was performed through February 2020. The main outcome measurements were diagnostic accuracy, cellularity, low blood contamination, adequate core tissue acquisition, and technical success rate. RESULTS: Eleven studies (including 6 randomized trials) were included, with a total of 504 patients who underwent SP and 551 who underwent SS. Diagnostic accuracy was significantly superior in the SP group, compared with the SS group [odds ratio (OR)=1.60; 95% confidence interval (CI), 1.14-2.26]. The SP group had higher pooled rates of low blood contamination (OR=1.93; 95% CI, 1.29-2.87) and adequate core tissue acquisition (OR=1.91; 95% CI, 1.11-3.26) than the SS group. There was no significant difference between groups in the adequacy of cellularity (OR=0.99; 95% CI, 0.63-1.57; P=0.98) or technical success rate (OR=0.38; 95% CI, 0.13-1.15; P=0.09). CONCLUSIONS: The authors provide evidence that SP is superior to SS in diagnostic accuracy, low blood contamination, and adequate core tissue acquisition, without reducing adequacy of cellularity or technical success rate.

Long noncoding RNA small nucleolar RNA host gene 12 promotes papillary thyroid carcinoma cell growth and invasion by targeting miR-16-5p.

Emerging evidence has shown that long noncoding RNA (lncRNA) plays an important role in various types of malignant cancer. Small nucleolar RNA host gene 12 (SNHG12) was found to be upregulated and to act as an oncogene in several cancers. However, the function and regulatory mechanism of SNHG12 remain unclear in papillary thyroid carcinoma (PTC). In this study, SNHG12 was found to be increased in PTC tissues and cell lines using quantitative real-time PCR. Knockdown of SNHG12 significantly inhibited PTC cell proliferation, migration and invasion and induced apoptosis in vitro. Mechanistic investigations revealed that SNHG12 functions as a competing endogenous RNA (ceRNA) to sponge miR-16-5p, which was downregulated in PTC tissues. In addition, rescue assays further confirmed that SNHG12 contributed to the progression of PTC through regulating miR-16-5p expression. These results indicated that SNHG12 might contribute to tumor progression in PTC by acting as a ceRNA to sponge miR-16-5p.

Development and Validation of an Automatic Image-Recognition Endoscopic Report Generation System: A Multicenter Study.

INTRODUCTION: Conventional gastrointestinal (GI) endoscopy reports written by physicians are time consuming and might have obvious heterogeneity or omissions, impairing the efficiency and multicenter consultation potential. We aimed to develop and validate an image recognition-based structured report generation system (ISRGS) through a multicenter database and to assess its diagnostic performance. METHODS: First, we developed and evaluated an ISRGS combining real-time video capture, site identification, lesion detection, subcharacteristics analysis, and structured report generation. White light and chromoendoscopy images from patients with GI lesions were eligible for study inclusion. A total of 46,987 images from 9 tertiary hospitals were used to train, validate, and multicenter test (6:2:2). Moreover, 5,699 images were prospectively enrolled from Qilu Hospital of Shandong University to further assess the system in a prospective test set. The primary outcome was the diagnosis performance of GI lesions in multicenter and prospective tests. RESULTS: The overall accuracy in identifying early esophageal cancer, early gastric cancer, early colorectal cancer, esophageal varices, reflux esophagitis, Barrett's esophagus, chronic atrophic gastritis, gastric ulcer, colorectal polyp, and ulcerative colitis was 0.8841 (95% confidence interval, 0.8775-0.8904) and 0.8965 (0.8883-0.9041) in multicenter and prospective tests, respectively. The accuracy of cecum and upper GI site identification were 0.9978 (0.9969-0.9984) and 0.8513 (0.8399-0.8620), respectively. The accuracy of staining discrimination was 0.9489 (0.9396-0.9568). The relative error of size measurement was 4.04% (range 0.75%-7.39%). DISCUSSION: ISRGS is a reliable computer-aided endoscopic report generation system that might assist endoscopists working at various hospital levels to generate standardized and accurate endoscopy reports (http://links.lww.com/CTG/A485).

MicroRNA-186-5p Inhibits Proliferation And Metastasis Of Esophageal Cancer By Mediating HOXA9.

OBJECTIVE: MicroRNA (miRNA) is an endogenous, non-coding small RNA that plays a key role in regulating organism biology and pathology. The aim of this study was to investigate the expression characteristics of microRNA-186-5p in esophageal cancer (ECa) and its correlation with clinical progression and prognosis, and to further explore its underlying mechanisms. METHODS: Real-time quantitative PCR (qRT-PCR) was used to detect microRNA-186-5p level in 45 pairs of ECa tissue samples and adjacent ones, and to analyze the expression of microRNA-186-5p and clinical progression of ECa and prognosis. The relationship between microRNA-186-5p level in ECa cell lines was further verified by qRT-PCR. Finally, the potential mechanism was explored using luciferase reporter gene assay and cell recovery experiment. RESULTS: QRT-PCR results revealed that the expression of microRNA-186-5p in ECa tissues was remarkably lower than that in adjacent tissues, and the difference was statistically significant. Compared with patients with high expression of microRNA-186-5p, patients with low expression of microRNA-186-5p had higher incidence of pathological stage and lower overall survival rate. Besides, compared with the miR-NC group, the microRNA-186-5p mimics group had a significant decrease in proliferation and metastasis ability of ECa cells. Subsequent qRT-PCR validation in ECa cell lines and tissues indicated a significant increase in HOXA9 expression and a negative correlation with microRNA-186-5p. CONCLUSION: The expression of microRNA-186-5p was remarkably decreased in ECa, which was remarkably correlated with pathological stage, distant metastasis and poor prognosis of ECa. The results suggested that microRNA-186-5p may inhibit cell proliferation of ECa by regulating HOXA9.

Cyclin-Dependent Kinase Inhibitor 3 Promoted Cell Proliferation by Driving Cell Cycle from G1 to S Phase in Esophageal Squamous Cell Carcinoma.

Background and aims. Cyclin-dependent kinase inhibitor 3 (CDKN3) has been found playing a varying role in carcinogenesis, but its biological function in esophageal squamous cell carcinoma (ESCC) is unclear. The aim of this study was to demonstrate the role of CDKN3 in ESCC. Materials and Methods: Real-time PCR and Western blot was performed in 15 pairs of ESCC tissues and adjacent normal esophageal tissues. Then cell proliferation ability, cloning ability, cell cycle status and migration and invasion ability were explored in CDKN3 overexpressed TE1 cell line and CDKN3 siRNA transfected TE1 and KYSE70 cell lines. Finally, cell cycle related proteins CyclinD1, CDK4, pAKT, P53, P21, and P27 were tested by Western blot. Results: mRNA level was higher in 11 ESCC tissues compared to adjacent normal tissues, and an increased protein expression was further detected in 8 of those 11 ESCC tissues. Functional assays showed that CDKN3 overexpression promoted ESCC cell proliferation, colony formation, migration and invasion, and facilitated G1/S transition. Opposite results were also got after transfected with CDKN3 siRNA. Cell cycle associated protein pAKT, CyclinD1, CDK4 and P27 were upregulated and P53, P21 and were downregulated under CDKN3 overexpression. All the protein levels were found changed in the opposite direction when CDKN3 expression was disturbed by siRNA. Conclusions: Our study suggested that CDKN3 acted as an oncogene in human ESCC and may accelerate the G1/S transition by affecting CyclinD-CDK4 complex via regulating pAKT-p53-p21 axis and p27 independent of AKT.

Crosstalk between Mitochondrial Fission and Oxidative Stress in Paraquat-Induced Apoptosis in Mouse Alveolar Type II Cells.

Paraquat (PQ), as a highly effective and nonselective herbicide, induces cell apoptosis through generation of superoxide anions which forms reactive oxygen species (ROS). Mitochondria, as regulators for cellular redox signaling, have been proved to play an important role in PQ-induced cell apoptosis. This study aimed to evaluate whether and how mitochondrial fission interacts with oxidative stress in PQ-induced apoptosis in mouse alveolar type II (AT-II) cells. Firstly, we demonstrated that PQ promoted apoptosis and release of cytochrome-c (Cyt-c). Furthermore, we showed that PQ broke down mitochondrial network, enhanced the expression of fission-related proteins, increased Drp1 mitochondrial translocation while decreased the expression of fusion-related proteins in AT-II cells. Besides, inhibiting mitochondrial fission using mdivi-1, a selective inhibitor of Drp1, markedly attenuated PQ-induced apoptosis, release of Cyt-c and the generation of ROS. These results indicate that mitochondrial fission involves in PQ-induced apoptosis. Further study demonstrated that antioxidant ascorbic acid inhibited Drp1 mitochondrial translocation, mitochondrial fission and attenuated PQ-induced apoptosis. Overall, our findings suggest that mitochondrial fission interplays with ROS in PQ-induced apoptosis in mouse AT-II cells and mitochondrial fission could serve as a potential therapeutic target in PQ poisoning.

Construction of disease-specific transcriptional regulatory networks identifies co-activation of four gene in esophageal squamous cell carcinoma.

Even though various molecules may serve as biomarkers, little is known concerning the mechanisms underlying the carcinogenesis of ESCC, particularly the transcriptional regulatory network. Thus, in the present study, paired ESCC and non-cancerous (NC) tissues were assayed by Affymetrix microarray assays. Passing Attributes between Networks for Data Assimilation (PANDA) was used to construct networks between transcription factors (TFs) and their targets. AnaPANDA program was applied to compare the regulatory networks. A hypergeometric distribution model-based target profile similarity analysis was utilized to find co-activation effects using both TF-target networks and differential expression data. There were 1,116 genes upregulated and 1,301 genes downregulated in ESCC compared with NC tissues. In TF-target networks, 16,970 ESCC-specific edges and 9,307 NC-specific edges were identified. Edge enrichment analysis by AnaPANDA indicated 17 transcription factors (NFE2L2, ELK4, PAX6, TLX1, ESR1, ZNF143, TP53, REL, ELF5, STAT1, TBP, NHLH1, FOXL1, SOX9, STAT3, ELK1, and HOXA5) suppressed in ESCC and 5 (SPIB, BRCA1, MZF1, MAFG and NFE2L1) activated in ESCC. For SPIB, MZF1, MAFG and NFE2L1, a strong and significant co-activation effect among them was detected in ESCC. In conclusion, the construction of transcriptional regulatory networks found SPIB, MZF1, MAFG and NFE2L1 co-activated in ESCC, which provides distinctive insight into the carcinogenesis mechanism of ESCC.

Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice.

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved. METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-xL mRNAs in the SAP group was decreased markedly, while the IL-22RA1 mRNA expression was increased significantly relative to the normal control group (P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-xL or IL-22RA1 mRNA (P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05). CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.