Weiming Xiao

Intratumor Hypoxia Promotes Immune Tolerance by Inducing Regulatory T Cells via TGF-β1 in Gastric Cancer

Regulatory T cell (Treg)-mediated immunosuppression represents one of the crucial tumor immune evasion mechanisms and is a main obstacle for successful tumor immunotherapy. Hypoxia, a common feature of solid tumors, has been associated with potentiated immunosuppression, decreased therapeutic response, malignant progression and local invasion. Unfortunately, the link between hypoxia and Treg-mediated immune tolerance in gastric cancer remains poorly understood. In our study, Tregs and hypoxia inducible factor-1α were found to be positively correlated with each other and were increased with the tumor progression. A subsequent in vitro study indicated that supernatants derived from gastric cancer cells under hypoxic condition, could induce the expression of Foxp3 via TGF-β1. These findings confirmed the crucial role of Tregs as a therapeutic target in gastric cancer therapy and provided helpful thoughts for the design of immunotherapy for gastric cancer in the future.

Induction of TGF-β and IL-10 production in dendritic cells using astilbin to inhibit dextran sulfate sodium-induced colitis

Astilbin, a major bioactive compound from Rhizoma smilacis glabrae, has been reported to possess anti-inflammatory properties. Our study first evaluated astilbin on dextran sulfate sodium (DSS)-induced acute colitis in mice. By intraperitoneal injection of astilbin, the severity of colitis was attenuated, and the serum levels of IL-10 and TGF-β were increased. Using flow cytometry, a higher number of IL-10(+) dendritic cells (DCs) and TGF-β(+) DCs and a lower number of CD86(+) DCs, IL-12 p40(+) DCs, and IL-1β(+) DCs were detected in the spleen of mice with colitis after astilbin treatment. The administration of astilbin also resulted in the upregulation of CD103(+) expression in colonic DCs. In a coculture system, murine bone marrow-derived DCs pretreated with astilbin resulted in an enhanced production of CD4(+)CD25(+)Foxp3(+) T cells. The results of this study show that astilbin could be a candidate drug for inflammatory bowel disease by mediating the regulatory functions of DCs.

NK1.1− CD4+ NKG2D+ T cells suppress DSS‐induced colitis in mice through production of TGF‐β

CD4+ NKG2D+ T cells are associated with tumour, infection and autoimmune diseases. Some CD4+ NKG2D+ T cells secrete IFN‐γ and TNF‐α to promote inflammation, but others produce TGF‐β and FasL to facilitate tumour evasion. Here, murine CD4+ NKG2D+ T cells were further classified into NK1.1− CD4+ NKG2D+ and NK1.1+ CD4+ NKG2D+ subpopulations. The frequency of NK1.1− CD4+ NKG2D+ cells decreased in inflamed colons, whereas more NK1.1+ CD4+ NKG2D+ cells infiltrated into colons of mice with DSS‐induced colitis. NK1.1− CD4+ NKG2D+ cells expressed TGF‐β and FasL without secreting IFN‐γ, IL‐21 and IL‐17 and displayed no cytotoxicity. The adoptive transfer of NK1.1− CD4+ NKG2D+ cells suppressed DSS‐induced colitis largely dependent on TGF‐β. NK1.1− CD4+ NKG2D+ cells did not expressed Foxp3, CD223 (LAG‐3) and GITR. The subpopulation was distinct from NK1.1+ CD4+ NKG2D+ cells in terms of surface markers and RNA transcription. NK1.1−CD4+ NKG2D+ cells also differed from Th2 or Th17 cells because the former did not express GATA‐3 and ROR‐γt. Thus, NK1.1− CD4+ NKG2D+ cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.

Synchronous vs sequential laparoscopic cholecystectomy for cholecystocholedocholithiasis

AIM To compare synchronous laparoscopic cholecystectomy (LC) combined with endoscopic sphincterotomy (EST) and sequential LC combined with EST for treating cholecystocholedocholithiasis. METHODS A total of 150 patients were included and retrospectively studied. Among these, 70 were selected for the synchronous operation, in which the scheme was endoscopic retrograde cholangiopancreatography combined with EST during LC. The other 80 patients were selected for the sequential operation, in which the scheme involved first cutting the papillary muscle under endoscopy and then performing LC. The indexes in the two groups, including the operation time, the success rate, the incidence of complications, and the length of the hospital stay, were observed. RESULTS There were no significant differences between the groups in terms of the numbers of patients, sex distribution, age, American Society of Anesthesiologists score, serum bilirubin, γ-glutamyl transpeptidase, mean diameter of common bile duct stones, and previous medical and surgical history (P = 0.54, P = 0.18, P = 0.52, P = 0.22, P = 0.32, P = 0.42, P = 0.68, P = 0.70, P = 0.47 and P = 0.57). There was no significant difference in the surgical operation time between the two groups (112.1 ± 30.8 min vs 104.9 ± 18.2 min). Compared with the sequential operation group, the incidence of pancreatitis was lower (1.4% vs 6.3%), the incidence of hyperamylasemia (1.4% vs 10.0%, P < 0.05) was significantly reduced, and the length of the hospital stay was significantly shortened in the synchronous operation group (3 d vs 4.5 d, P < 0.001). CONCLUSION For treatment of cholecystocholedocholithiasis, synchronous LC combined with EST reduces incidence of complications, decreases length of hospital stay, simplifies the surgical procedure, and reduces operation time.

Isoliquiritigenin Ameliorates Acute Pancreatitis in Mice via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway

Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.

Prevalence and clinical characteristics of fatty pancreas in Yangzhou, China: A cross-sectional study

OBJECTIVE The aim of this study was to investigate the prevalence and risk factors of fatty pancreas in Yangzhou, China. METHODS This was a cross-sectional study. Initially, 2093 subjects were included in the study. After the exclusion of 865 subjects based on incomplete information, a total of 1228 subjects were selected for further analysis. The subjects were stratified into two groups (the fatty pancreas group and the non-fatty pancreas group) based on the results. Anthropometric and biochemical findings were compared between the groups. RESULTS Among the 2093 study subjects, 56 (2.7%) had fatty pancreas. Overall, 53 out of 1228 subjects were diagnosed with fatty pancreas and included into the fatty pancreas group. Univariate analysis showed significant differences in age and the prevalence of general obesity, central obesity, alcohol consumption, metabolic syndrome and fatty liver between the two groups (all p < 0.01). The fatty pancreas group had higher levels of aspartate aminotransferase, alanine aminotransferase, serum uric acid, fasting blood glucose, total cholesterol, triglycerides and low-density lipoprotein, and lower levels of high-density lipoprotein than did the non-fatty pancreas group (all p < 0.05). Multivariate logistic regression analysis showed that age (p = 0.007), central obesity (p = 0.002) and fatty liver (p = 0.006) were independent risk factors for fatty pancreas, with odds ratios (ORs) of 1.034 (95% confidence interval (CI): 1.009-1.059), 5.364 (95% CI: 1.890-15.227), and 2.666 (95% CI: 1.332-5.338), respectively. CONCLUSION The prevalence of fatty pancreas in the examined population is approximately 2.7%. Increased age, central obesity and fatty liver disease are independent risk factors for fatty pancreas.

The Impact of Colonoscopy Quality Control Table on Adenoma Detection Rates

Objective. This study aims to investigate the effects of reporting colonoscopy findings and the regular review of outcomes on adenoma detection rates. Methods. Patients who underwent colonoscopy from August 2013 to February 2014 were selected as the intervention group. The preintervention group included patients who underwent colonoscopy from January 2013 to July 2013, in which the procedure sheet for this group of patients was not accomplished. The primary outcome was adenoma detection rate (ADR), and secondary outcomes included the success rate of intubation and withdrawal time. Results. This study included 2,467 cases: 1,302 cases in the intervention group and 1,165 cases in the preintervention group. There was no significant difference in demographic characteristics between the two groups. In the intervention group, withdrawal time of colonoscopy was longer (P < 0.01), and the success rate of intubation (92.5% versus 89.1%, P < 0.05) and detection rate of polyps (32.6% versus 27.6%, P < 0.05) and adenomas (20.0% versus 16.1%, P < 0.05) were higher. Significantly high detection rates for proximal adenomas, flat adenomas, and adenomas with a diameter <5 mm were observed in the intervention group (all P < 0.01). Conclusion. The reporting and review of procedure details help to improve quality indicators of colonoscopy.

Significant increased CA199 levels in acute pancreatitis patients predicts the presence of pancreatic cancer

Background and study aims Carbohydrate antigen 19-9 (CA199) has been identified as a tumor marker for pancreatic cancer but also increases in benign lesions of the digestive system. However, literature associated with the relationship between CA199 and acute pancreatitis (AP) is limited. This study aimed to focus on serum CA199 level measurements in AP patients and the associated clinical significance. Materials and methods From January 2006 to December 2015, 1,609 consecutive patients with AP were admitted to our department and included in the study. The relationships among the etiology of AP, the disease severity, the incidence of pancreatic cancer during hospitalization and CA199 levels were analyzed. Results Serum CA199 levels were measured for 693 of 1,609 AP patients. Of those patients, 186 (26.8%) had elevated CA199 levels (> 37 U/ml). Patients with high CA199 levels were older and had predominantly biliary causes in comparison with patients with normal CA199 levels. There were no definite specific correlations between CA199 levels and disease severity in AP. In addition, serum levels of CA199 positively correlated with serum alanine aminotransferase, aspartate transaminase, glutamyl transpeptidase, alkaline phosphatase and creatinine levels. After stratification, the incidence of pancreatic cancer increased proportionally to CA199 levels in AP patients. Conclusions Serum CA199 levels was elevated in patients with AP, especially in patients with biliary pancreatitis. AP patients with significantly increased CA199 levels may have a higher risk for the presence of pancreatic cancer. We recommended routinely monitoring CA199 levels during hospitalization for AP patients.

Corrigendum to “Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway”

[This corrects the article DOI: 10.1155/2018/3048532.].

Regulatory NK1.1−CD4+NKG2D+ subset induced by NKG2DL+ cells promotes tumor evasion in mice

Regulatory T cells play critical roles in self-tolerance and tumor evasion. CD4+NKG2D+ cells with regulatory activity are present in patients with NKG2DL+ tumors and juvenile systemic lupus erythematosus. We previously showed that TGF-β-producing CD4+NKG2D+ T cells are present in pCD86-Rae-1ε transgenic mice. Here, we performed both ex vivo and in vivo studies on pCD86-Rae-1ε transgenic mice and an MC38 tumor-bearing mouse model and show that NK1.1−CD4+NKG2D+ T cells have regulatory activity in pCD86-Rae-1ε transgenic mice. Furthermore, this T-cell subset was induced in mice transplanted with NKG2DL+ tumor cells and produced TGF-β and FasL, and secreted low amounts of IFN-γ. This T-cell subset downregulated the function of effector T cells and dendritic cells, which were abolished by anti-TGF-β antibody. In vivo, adoptive transfer of NK1.1−CD4+NKG2D+ T cells promoted TGF-β-dependent tumor growth in mice. We further found that ex vivo induction of NK1.1−CD4+NKG2D+ T cells was dependent on both anti-CD3 and NKG2DL stimulation. Furthermore, regulatory NK1.1−CD4+NKG2D+ T cells did not express Foxp3 or CD25 and expressed intermediate levels of T-bet. Western-blotting showed that STAT3 signaling was activated in NK1.1−CD4+NKG2D+ T cells of MC38 tumor-bearing and pCD86-Rae-1ε transgenic mice. In conclusion, we describe a regulatory NK1.1−CD4+NKG2D+ T-cell population, different from other regulatory T cells and abnormally elevated in pCD86-Rae-1ε transgenic and MC38 tumor-bearing mice.