AIM: To investigate the relationship between serum soluble interleukin-2 receptor (sIL-2R) level and anti-HBc in patients with chronic hepatitis B virus (HBV) infection. METHODS: Sera from 100 patients with chro...AIM: To investigate the relationship between serum soluble interleukin-2 receptor (sIL-2R) level and anti-HBc in patients with chronic hepatitis B virus (HBV) infection. METHODS: Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg (+), HBeAg (+) and anti-HBc (+), n = 50] and group B [HBsAg (+), HBeAg (+) and anti-HBc (-), n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase (ALT) were also detected. RESULTS: Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg (+), HBeAg (+) and antiHBc (+) (976.56±213.51×10^3 U/L) than in patients with HBsAg (+), HBeAg (+) and anti-HBc (-) (393.41±189.54 ×10^3 U/L, P〈 0.01). A significant relationship was found between serum sIL-2R and ALT levels (P〈 0.01) in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients (P〈 0.01). CONCLUSION: The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.展开更多
Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function...Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function.Chronic inflammation has been demonstrated to be the pathological basis of fibrosis.Emerging studies have revealed that most interleukin-17(IL-17)isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity.Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes,including the initiation and exacerbation of IPF.Here,we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.展开更多
AIM: To examine the contribution of toll-like receptors(TLRs) expression and activation to the prolonged inflammation often seen in human diabetic wounds.METHODS: Debridement wound tissue was collected from diabetic p...AIM: To examine the contribution of toll-like receptors(TLRs) expression and activation to the prolonged inflammation often seen in human diabetic wounds.METHODS: Debridement wound tissue was collected from diabetic patients with informed consent. Total RNA and protein were isolated and subjected to real-time polymerase chain reaction and Western blot analyses. RESULTS: TLR1, 2, 4, and 6 mRNA expressions were increased significantly in wounds of diabetic patients compared with non-diabetic wounds(P 【 0.05). MyD88 protein expression was significantly increased in diabetic wounds compared to non-diabetic wounds. Interleukin-1beta, tumor necrosis factor-alpha concentration nuclear factor-kappa B activation, and thiobarbituric acid reactive substances were increased in diabetic wounds compared to non-diabetic wounds(P 【 0.01). CONCLUSION: Collectively, our novel findings show that increased TLR expression, signaling, and activation may contribute to the hyper inflammation in the human diabetic wounds.展开更多
The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor(IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis(UC) and con-trols, and evaluate their r...The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor(IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis(UC) and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein(CRP) levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17 R m RNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls(P〈0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase(P〈0.05), and correlated with CRP levels(r=0.578, P〈0.01). IL-17 R expression levels were higher in active UC patients than in healthy con-trols(P〈0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.展开更多
Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodi...Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.展开更多
Objective:To study the correlation of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 expression with the illness in patients with chronic hepatitis b (CHB).Methods: A total of 48 patients who were diagnosed w...Objective:To study the correlation of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 expression with the illness in patients with chronic hepatitis b (CHB).Methods: A total of 48 patients who were diagnosed with chronic hepatitis b in Jianyang People's Hospital between July 2014 and January 2017 were selected as the CHB group of the research, 66 healthy volunteers who received physical examination during the same period were selected as control group, the peripheral blood was collected to determine Th17 cell surface CCR4, CCR6 and CXCR3 expression, and serum was collected to determine the levels of Th17 cytokines, liver function indexes and liver fibrosis indexes.Results: Peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity of CHB group were significantly higher than those of control group;serum IL-17, IL-21, IL-22, ALT, AST, GLB, HA, PC-Ⅲ, LN and C-Ⅳ levels of CHB group were significantly higher than those of control group and positively correlated with peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity while serum ALB level was significantly lower than that of control group and negatively correlated with peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity.Conclusion: The high expression of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 in patients with CHB can result in increased secretion of Th17 cytokines, liver function injury and liver fibrosis.展开更多
Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the product...Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.展开更多
AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned t...AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-kappa B p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 +/- 0.54 vs 1.20 +/- 0.44, 0.60 +/- 0.54 vs 1.80 +/- 0.45, 0.60 +/- 0.54 vs 3.0 +/- 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 +/- 8.75 vs 76.61 +/- 3.58, 105.46 +/- 8.75 vs 69.78 +/- 1.87, 105.46 +/- 8.75 vs 67.41 +/- 1.84, respectively, P < 0.01 for IL-8; and 30.83 +/- 1.29 vs 75.64 +/- 1.90, 30.83 +/- 1.29 vs 80.90 +/- 3.16, 30.83 +/- 1.29 vs 83.46 +/- 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-kappa B p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons (0.492 +/- 0.026 vs 0.380 +/- 0.022, 0.492 +/- 0.026 vs 0.355 +/- 0.005, 0.492 +/- 0.026 vs 0.327 +/- 0.015, respectively, P < 0.05 for TLR9; and 0.436 +/- 0.041 vs 0.326 +/- 0.022, 0.436 +/- 0.041 vs 0.293 +/- 0.006, 0.436 +/- 0.041 vs 0.265 +/- 0.017, respectively, P < 0.05 for NF-kappa B p65). CONCLUSION: Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-kappa B p65 in UC rats. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to dete...Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.展开更多
Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)i...Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.展开更多
基金Supported by the Namral Science Foundation of Gansu Province,No.ZR-96-078
文摘AIM: To investigate the relationship between serum soluble interleukin-2 receptor (sIL-2R) level and anti-HBc in patients with chronic hepatitis B virus (HBV) infection. METHODS: Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg (+), HBeAg (+) and anti-HBc (+), n = 50] and group B [HBsAg (+), HBeAg (+) and anti-HBc (-), n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase (ALT) were also detected. RESULTS: Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg (+), HBeAg (+) and antiHBc (+) (976.56±213.51×10^3 U/L) than in patients with HBsAg (+), HBeAg (+) and anti-HBc (-) (393.41±189.54 ×10^3 U/L, P〈 0.01). A significant relationship was found between serum sIL-2R and ALT levels (P〈 0.01) in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients (P〈 0.01). CONCLUSION: The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.
基金Natural Science Foundation of Jiangsu Province(BK20180616)the Joint Funds for the Health and Education of Fujian Province(2019-WJ-31)the Institute of Respiratory Diseases,Xiamen Medical College(HXJB-15).
文摘Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function.Chronic inflammation has been demonstrated to be the pathological basis of fibrosis.Emerging studies have revealed that most interleukin-17(IL-17)isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity.Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes,including the initiation and exacerbation of IPF.Here,we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.
文摘AIM: To examine the contribution of toll-like receptors(TLRs) expression and activation to the prolonged inflammation often seen in human diabetic wounds.METHODS: Debridement wound tissue was collected from diabetic patients with informed consent. Total RNA and protein were isolated and subjected to real-time polymerase chain reaction and Western blot analyses. RESULTS: TLR1, 2, 4, and 6 mRNA expressions were increased significantly in wounds of diabetic patients compared with non-diabetic wounds(P 【 0.05). MyD88 protein expression was significantly increased in diabetic wounds compared to non-diabetic wounds. Interleukin-1beta, tumor necrosis factor-alpha concentration nuclear factor-kappa B activation, and thiobarbituric acid reactive substances were increased in diabetic wounds compared to non-diabetic wounds(P 【 0.01). CONCLUSION: Collectively, our novel findings show that increased TLR expression, signaling, and activation may contribute to the hyper inflammation in the human diabetic wounds.
基金supported by the National Natural Science Foundation of China(No.81200283)
文摘The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor(IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis(UC) and con-trols, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein(CRP) levels were determined by ELISA and immu-nonephelometry, respectively. The IL-17 R m RNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls(P〈0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase(P〈0.05), and correlated with CRP levels(r=0.578, P〈0.01). IL-17 R expression levels were higher in active UC patients than in healthy con-trols(P〈0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.
文摘Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.
文摘Objective:To study the correlation of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 expression with the illness in patients with chronic hepatitis b (CHB).Methods: A total of 48 patients who were diagnosed with chronic hepatitis b in Jianyang People's Hospital between July 2014 and January 2017 were selected as the CHB group of the research, 66 healthy volunteers who received physical examination during the same period were selected as control group, the peripheral blood was collected to determine Th17 cell surface CCR4, CCR6 and CXCR3 expression, and serum was collected to determine the levels of Th17 cytokines, liver function indexes and liver fibrosis indexes.Results: Peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity of CHB group were significantly higher than those of control group;serum IL-17, IL-21, IL-22, ALT, AST, GLB, HA, PC-Ⅲ, LN and C-Ⅳ levels of CHB group were significantly higher than those of control group and positively correlated with peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity while serum ALB level was significantly lower than that of control group and negatively correlated with peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 fluorescence intensity.Conclusion: The high expression of peripheral blood Th17 cell surface CCR4, CCR6 and CXCR3 in patients with CHB can result in increased secretion of Th17 cytokines, liver function injury and liver fibrosis.
基金supported by the National Natural Science Foundation of China(No.82103756).
文摘Objective Proprionibacterium acnes(P.acnes)-induced inflammatory responses,proliferation and differentiation of keratinocytes contribute to the progression of acne vulgaris(AV).P.acnes was found to enhance the production of interleukin-8(IL-8)by keratinocytes.This study aimed to investigate the role of IL-8 in P.acnes-induced proliferation and differentiation of keratinocytes and the underlying mechanism.Methods The P.acnes-stimulated HaCaT cell(a human keratinocyte cell line)model was established.Western blotting and immunofluorescence were performed to detect the expression of the IL-8 receptors C-X-C motif chemokine receptor 1(CXCR1)and C-X-C motif chemokine receptor 2(CXCR2)on HaCaT cells.Cell counting kit-8(CCK-8)assay,5-ethynyl-20-deoxyuridine(EdU)assay and Western blotting were performed to examine the effects of IL-8/CXCR2 axis on the proliferation and differentiation of HaCaT cells treated with P.acnes,the IL-8 neutralizing antibody,the CXCR2 antagonist(SB225002),or the CXCR1/CXCR2 antagonist(G31P).Western blotting,nuclear and cytoplasmic separation,CCK-8 assay,and EdU assay were employed to determine the downstream pathway of CXCR2 after P.acnes-stimulated HaCaT cells were treated with the CXCR2 antagonist,the protein kinase B(AKT)antagonist(AZD5363),or the constitutively active forkhead box O1(FOXO1)mutant.Finally,autophagy markers were measured in HaCaT cells following the transfection of the FOXO1 mutant or treatment with the autophagy inhibitor 3-methyladenine(3-MA).Results The expression levels of CXCR1 and CXCR2 were significantly increased on the membrane of HaCaT cells following P.acnes stimulation.The IL-8/CXCR2 axis predominantly promoted the proliferation and differentiation of P.acnes-induced HaCaT cells by activating AKT/FOXO1/autophagy signaling.In brief,IL-8 bound to its receptor CXCR2 on the membrane of keratinocytes to activate the AKT/FOXO1 axis.Subsequently,phosphorylated FOXO1 facilitated autophagy to promote the proliferation and differentiation of P.acnes-induced keratinocytes.Conclusion This study demonstrated the novel autocrine effect of IL-8 on the proliferation and differentiation of P.acnes-induced keratinocytes,suggesting a potential therapeutic target for AV.
基金Supported by Scientific and Technological Project of Educational Department of Liaoning Province,China,No.L2011166
文摘AIM: To investigate the efficacy of moxibustion in ulcerative colitis (UC) rats from morphological, immunological and molecular biological perspectives. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group (normal rats, n = 6) and a model replication (MR) group (UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion (9M) group (9 moxa-cone, n = 6), 6-min moxibustion (6M) group (6 moxa-cone, n = 6), 3-min moxibustion (3M) group (3 moxa-cone, n = 6), and a waiting list control (WLC) group (no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin (IL)-8 and IL-10, and expression of Toll-like receptor (TLR)9 as well as nuclear factor (NF)-kappa B p65 in colonic tissue were determined by disease activity index (DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively. RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment (3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons (0.60 +/- 0.54 vs 1.20 +/- 0.44, 0.60 +/- 0.54 vs 1.80 +/- 0.45, 0.60 +/- 0.54 vs 3.0 +/- 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons (105.46 +/- 8.75 vs 76.61 +/- 3.58, 105.46 +/- 8.75 vs 69.78 +/- 1.87, 105.46 +/- 8.75 vs 67.41 +/- 1.84, respectively, P < 0.01 for IL-8; and 30.83 +/- 1.29 vs 75.64 +/- 1.90, 30.83 +/- 1.29 vs 80.90 +/- 3.16, 30.83 +/- 1.29 vs 83.46 +/- 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-kappa B p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons (0.492 +/- 0.026 vs 0.380 +/- 0.022, 0.492 +/- 0.026 vs 0.355 +/- 0.005, 0.492 +/- 0.026 vs 0.327 +/- 0.015, respectively, P < 0.05 for TLR9; and 0.436 +/- 0.041 vs 0.326 +/- 0.022, 0.436 +/- 0.041 vs 0.293 +/- 0.006, 0.436 +/- 0.041 vs 0.265 +/- 0.017, respectively, P < 0.05 for NF-kappa B p65). CONCLUSION: Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-kappa B p65 in UC rats. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
文摘Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.
基金supported by grants from the National Natural Science Foundation of China,No.81971231(to JL)Liaoning Revitalization Talents Program,No.XLYC1907178(to JL)。
文摘Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.