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The activation of the P2X7 receptor as an ATP-gated ion channel,triggers the release of pro-inflammato-ry cytokines in tumor carring individuals and stimulate excitation of injury-causing neurons,thereby exacerbating the transmission of pain.In preclinical cancer pain models,it has the potential to serve as a new therapeutic target for cancer pain management.
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Background/Aims@#Interleukin-22 (IL-22) is an important cytokine maintaining homeostasis at barrier surfaces. In this study, the role of IL-22 in acute pancreatitis-associated intestinal injury was further explored. @*Methods@#Severe acute pancreatitis (SAP) was induced by administration of L-arginine in Balb/c mice at different time gradients. Histopathological examinations were made in both the pancreas and small intestine. Furthermore, recombinant murine IL-22 (rIL-22) was administrated to L-arginine-induced SAP mice by intraperitoneal injection. The mRNA levels of IL-22R1, Reg-IIIβ,Reg-IIIγ, Bcl-2, and Bcl-xL were detected in the small intestine by real-time polymerase chain reaction, and protein levels of total and phosphorylated STAT3 were assessed via Western blot. @*Results@#Compared with normal control group, 72 hours of L-arginine exposure induced the most characteristic histopathological changes of SAP, evidenced by pathological changes and serum amylase levels. Meanwhile, significant pancreatitis-associated intestinal mucosa injury was also observed. The gene expression levels of antimicrobial proteins Reg-IIIβ, Reg-IIIγ and anti-apoptosis proteins Bcl-2, Bcl-xL were downregulated in small intestine. Furthermore, Larginine-induced SAP was attenuated by rIL-22 treatment. Importantly, pancreatitis-associated intestinal mucosa injury was also ameliorated, reflected by improved pathological changes and significant increase in gene expression levels of Reg-IIIβ, Reg-IIIγ, Bcl-2 and Bcl-xL. Consistently, serum amylase levels and mortality were decreased in mice treated with rIL-22. Mechanistically, the upregulated expressions of these protective genes were achieved by activating STAT3. @*Conclusions@#Exogenous rIL-22 attenuates L-arginine-induced acute pancreatitis and intestinal mucosa injury in mice, via activating STAT3 signaling pathway and enhancing the expression of antimicrobial peptides and antiapoptotic genes.
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Background/Aims@#Interleukin-22 (IL-22) is an important cytokine maintaining homeostasis at barrier surfaces. In this study, the role of IL-22 in acute pancreatitis-associated intestinal injury was further explored. @*Methods@#Severe acute pancreatitis (SAP) was induced by administration of L-arginine in Balb/c mice at different time gradients. Histopathological examinations were made in both the pancreas and small intestine. Furthermore, recombinant murine IL-22 (rIL-22) was administrated to L-arginine-induced SAP mice by intraperitoneal injection. The mRNA levels of IL-22R1, Reg-IIIβ,Reg-IIIγ, Bcl-2, and Bcl-xL were detected in the small intestine by real-time polymerase chain reaction, and protein levels of total and phosphorylated STAT3 were assessed via Western blot. @*Results@#Compared with normal control group, 72 hours of L-arginine exposure induced the most characteristic histopathological changes of SAP, evidenced by pathological changes and serum amylase levels. Meanwhile, significant pancreatitis-associated intestinal mucosa injury was also observed. The gene expression levels of antimicrobial proteins Reg-IIIβ, Reg-IIIγ and anti-apoptosis proteins Bcl-2, Bcl-xL were downregulated in small intestine. Furthermore, Larginine-induced SAP was attenuated by rIL-22 treatment. Importantly, pancreatitis-associated intestinal mucosa injury was also ameliorated, reflected by improved pathological changes and significant increase in gene expression levels of Reg-IIIβ, Reg-IIIγ, Bcl-2 and Bcl-xL. Consistently, serum amylase levels and mortality were decreased in mice treated with rIL-22. Mechanistically, the upregulated expressions of these protective genes were achieved by activating STAT3. @*Conclusions@#Exogenous rIL-22 attenuates L-arginine-induced acute pancreatitis and intestinal mucosa injury in mice, via activating STAT3 signaling pathway and enhancing the expression of antimicrobial peptides and antiapoptotic genes.
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Objective:To explore the peripheral blood levels changes of soluble glycosylation end product receptor (sRAGE), endotoxin and Toll-like receptor (TLR) in patients with severe acute pancreatitis (SAP) complicated with peritoneal cavity infection, and clarify the relationship between indexes and pathogenetic condition.Methods:The clinical data of 105 patients with SAP in Shanghai Pudong New Area People′s Hospital from January 2017 to December 2020 were retrospectively analyzed. Among them, 28 cases had peritoneal cavity infection (infection group), and 77 cases had peritoneal cavity infection symptoms but undiagnosed (non-infection group). The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) at admission was recorded. When patients had the suspected symptoms and signs of peritoneal cavity infection, the serum levels of sRAGE, endotoxin, TLR4 and TLR9 were detected by enzyme-linked immunosorbent assay. The correlation between serum levels of sRAGE, endotoxin, TLR-4, TLR-9 and APACHE Ⅱ was analyzed by Pearson analysis; the risk factors of peritoneal cavity infection in SAP patients were analyzed by multivariate Logistic regression; the receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of serum sRAGE, endotoxin, TLR-4 and TLR-9 in peritoneal cavity infection were evaluated in patients with SAP; the Kaplan-Meier survival curve was drawn, and the comparison used log-rank test.Results:The serum sRAGE, endotoxin, TLR-4 and TLR-9 in infection group were significantly higher than those in non-infection group: (822.16 ± 104.51) ng/L vs. (728.09 ± 96.47) ng/L, (62.59 ± 20.11) ng/L vs. (41.62 ± 13.64) ng/L, (45.17 ± 8.54) μg/L vs. (37.34 ± 6.22) μg/L, (26.35 ± 6.73) μg/L vs. (20.02 ± 5.49) μg/L, and there were statistical differences ( P<0.01). Pearson correlation analysis result showed that the serum sRAGE, endotoxin, TLR-4 and TLR-9 were positively correlated with APACHE Ⅱ in patients with SAP ( r = 0.632, 0.556, 0.521 and 0.631; P<0.05). Multivariate Logistic regression analysis result showed that the combined organ function damage, shock, hypoxemia and serum sRAGE, endotoxin, TLR-4 and TLR-9 were independent risk factors of peritoneal cavity infection in patients with SAP ( P<0.05). ROC curve analysis result showed that the area under the curve for the serum sRAGE, endotoxin, TLR-4 and TLR-9 combined diagnosis of peritoneal cavity infection in patients with SAP was the largest, which was 0.910 (95% CI 0.838 to 0.957, P<0.01), with a sensitivity of 82.14% and a specificity of 87.01%. According to the ROC curve cut-off value of serum sRAGE, endotoxin, TLR-4 and TLR-9 (764.58 ng/L, 58.01 ng/L, 40.24 μg/L and 22.61 μg/L), the 28 patients with SAP complicated with peritoneal cavity infection were divided into high levels patients (21, 14, 23 and 22 cases) and low levels patients (7, 14, 5 and 6 cases); Kaplan-Meier survival curve analysis result showed that the 28-day survival rates in patients with high levels of sRAGE, endotoxin, TLR-4 and TLR-9 were significantly lower than those in patients with low levels (61.90% vs. 71.43%, 50.00% vs. 78.57%, 60.87% vs. 80.00% and 59.09% vs. 83.33%), and there were statistical differences ( P<0.05). Conclusions:The serum sRAGE, endotoxin, TLR-4 and TLR-9 have a high combined diagnostic value in SAP complicated with peritoneal cavity infection, and they are all related to the severity of the disease and have a significant impact on survival.
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Objective To analyze fungal isolates from patients with superficial fungal infections during 1960-2006.Methods Fungal strains isolated from patients with superficial (mucocutaneous and cutaneous)fungal infections and identified in the Medical Mycology Clinical Laboratory,Department of Dermatology and Venereology,Union Hospital,from 1960 to 2006 (data from September 1991 to July 1992 were unavailable),were subjected to a classification and statistical analysis.Clinical samples for mycological examination were taken from outpatients or inpatients of different departments in hospitals of Hubei province and surrounding areas.Morphological,physiological and biochemical methods were applied for species identification.Results A total of 11 989 Candida strains were isolated,which belonged to 23 species and 16 genera.They fell into 3 groups,i.e.,dermatophytes,Candida and yeasts (including Malassezia),and non-dermatophyte moulds.Since 287 strains of moulds were suspected to be contaminating fungi,11 702 residual isolates were analyzed.Of the analyzed isolates,Candida species (5642/11 702,48.2% )and dermatophytes (5279/11 702,45.1% )predominated,followed by yeasts (449/11 702,3.8%) and Malassezia species (332/11 702,2.8%).The most frequently isolated species was Trichophyton rubrum (3865/11 702,33.0%),Candida albicans (3110/11 702,26.6% ) and non-albicans Candida species (2532/11 702,21.6% ).Dermatophyte strains were mostly isolated from lesions of smooth skin with an exception of palmoplantar and interdigit regions (1787/5279,37.7%).The most common dermatophyte species was Trichophyton rubrum,followed by Trichophyton violanceum.Candida was mainly isolated from mucous membrane lesions (4099/5642,72.7%),with Candida albicans being the predominant species.Conclusions Candida species and dermatophytes predominate in patients with superficial fungal infections during 1960-2006,with Trichophyton rubrum being the most common species.