Identification of novel immune-related targets mediating disease progression in acute pancreatitis

IntroductionAcute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear.MethodsAn integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo.ResultsThe numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 × 10–3), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 × 10–8), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation.DiscussionIn summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression

Determinants of SARS-CoV-2 receptor gene expression in upper and lower airways

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.</p

Determinants of expression of SARS-CoV-2 entry-related genes in upper and lower airways.

Funder: Dutch Research Council (NWO)Funder: Cancer Research UK Cambridge CentreFunder: ATS Foundation/Boehringer Ingelheim Pharmaceuticals Inc. Research FellowshipFunder: The Netherlands Ministry of Spatial Planning, Housing, and the EnvironmentFunder: Chan Zuckerberg InitiativeFunder: The Netherlands Ministry of Health, Welfare, and SportFunder: Longfonds Junior FellowshipFunder: Cambridge BioresourceFunder: The Netherlands Organization for Health Research and DevelopmentFunder: Cambridge NIHR Biomedical Research CentreFunder: Parker B. Francis FellowshipFunder: China Scholarship Counci

The Diagnostic Value of Serum Gastrin-17 and Pepsinogen for Gastric Cancer Screening in Eastern China

Objective. To evaluate the diagnostic value of gastrin-17 (G-17) and pepsinogen (PG) in gastric cancer (GC) screening in China, especially eastern China, and to determine the best diagnostic combination and threshold (cutoff values) to screen out patients who need gastroscopy. Methods. The serum concentrations of G-17 and pepsinogen I and II (PGI and PGII) in 834 patients were analyzed, and the PGI/PGII ratio (PGR) was calculated. According to pathological results, patients can be divided into chronic nonatrophic gastritis (NAG)/chronic atrophic gastritis (CAG)/intraepithelial neoplasia (IN)/GC groups. The differences in G-17, PG, and PGR in each group were analyzed, and their values in GC diagnosis were evaluated separately and in combination. Results. There were differences in serum G-17, PGII, and PGR among the four groups (NAG/CAG/IN/GC) (P≤0.001). In total, 54 GC cases were diagnosed, of which 50% were early GC. There was no significant difference in the PGI levels among the four groups (P=0.377). NAG and CAG composed the chronic gastritis (CG) group. The G-17 and PGII levels in the IN and GC groups were higher than those in the CG group (both P≤oth C), while the PGR levels were lower (P≤lower). When distinguishing NAG from CAG, the best cutoff value for G-17 was 9.25 pmol/L, PGII was 7.06 μg/L, and PGR was 12.07. When distinguishing CG from IN, the best cutoff value for G-17 was 3.86 pmol/L, PGII was 11.92 μg/L, and PGR was 8.26. When distinguishing CG from GC, the best cutoff value for G-17 was 3.89 pmol/L, PGII was 9.16 μg/L, and PGR was 14.14. The sensitivity, specificity, accuracy, and positive and negative predictive values of G-17/PGII/PGR for GC diagnosis were 83.3%/70.4%/79.6%, 51.8%/56.3%/47.8%, 53.8%/57.2%/49.9%, 10.7%/10.9%/9.6%, and 97.8%/96.5%/97.1%, respectively. The sensitivity, specificity, accuracy, and positive predictive and negative predictive values of PGII/G-17 vs. PGR/G-17 vs. PGR/PGII in the diagnosis of GC were 63.0% vs. 70.4% vs. 64.8%, 70.5% vs. 70.1% vs. 60.4%, 70.0% vs. 70.1% vs. 60.7%, 12.9% vs. 14.0% vs. 10.2%, and 96.5% vs. 97.2% vs. 96.1%, respectively. Conclusion. The PGII and G-17 levels in patients with gastric IN and GC were significantly increased, while the serum PGR level was significantly decreased. Serological detection is effective for screening GC. The combination of different markers can improve the diagnostic efficiency. The highest diagnostic accuracy was G-17 combined with PGR, and the best cutoff values were G−17>3.89 pmol/L and PGR<14.14

Optical and Electrical Properties of Ag-Doped In 2

Ag-doped In2S3 (In2S3:Ag) thin films have been deposited onto glass substrates by a thermal evaporation method. Ag concentration is varied from 0 at.% to 4.78 at.%. The structural, optical, and electrical properties are characterized using X-ray diffraction (XRD), spectrophotometer, and Hall measurement system, respectively. The XRD analysis confirms the existence of In2S3 and AgIn5S8 phases. With the increase of the Ag concentration, the band gap of the films is decreased gradually from 2.82 eV to 2.69 eV and the resistivity drastically is decreased from ~103 to 5.478×10-2 Ω·cm

Discharge characteristics of an atmospheric pulsed microwave Ar/CF4 plasma jet

The atmospheric fluorocarbon plasma is widely used in surface modification of polymers. Recently, the pulsed microwave Ar/CF4 plasma jet is proved to be a promising atmospheric fluorocarbon plasma source with good performance. In this paper, the discharge characteristics of the pulsed microwave Ar/CF4 plasma jet are studied systematically. The discharge morphologies, ionization processes, optical emission spectra, and electron densities are obtained by a digital camera, an intensified charge coupled device, a fiber spectrometer, and a home-made microwave Rayleigh scattering device, respectively. The influences of the plasma operation parameters on the discharge characteristics are investigated, and the microwave input power and CF4 volume fraction are optimized. The results provide a basis for the generation and surface modification application of high-performance atmospheric fluorocarbon plasma

Table_1_Identification of novel immune-related targets mediating disease progression in acute pancreatitis.xls

IntroductionAcute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear.MethodsAn integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo.ResultsThe numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 × 10–3), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 × 10–8), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation.DiscussionIn summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression.</p