Background:Liver regeneration is a fundamental process for sustained body homeostasis and liver function recovery after injury.Emerging evidence demonstrates that myeloid cells play a critical role in liver regenerati...Background:Liver regeneration is a fundamental process for sustained body homeostasis and liver function recovery after injury.Emerging evidence demonstrates that myeloid cells play a critical role in liver regeneration by secreting cytokines and growth factors.Peroxisome proliferator-activated receptorα(PPARα),the target of clinical lipid-lowering fibrate drugs,regulates cell metabolism,proliferation,and survival.However,the role of myeloid PPARαin partial hepatectomy(PHx)-induced liver regeneration remains unknown.Methods:Myeloid-specific PPARa-deficient(Ppara^(Mye−/−))mice and the littermate controls(Ppara^(fl/fl))were subjected to sham or 2/3 PHx to induce liver regeneration.Hepatocyte proliferation and mitosis were assessed by immunohistochemical(IHC)staining for 5-bromo-2'-deoxyuridine(BrdU)and Ki67 as well as hematoxylin and eosin(H&E)staining.Macrophage and neutrophil infiltration into livers were reflected by IHC staining for galectin-3 and myeloperoxidase(MPO)as well as flow cytometry analysis.Macrophage migration ability was evaluated by transwell assay.The mRNA levels for cell cycle or inflammation-related genes were measured by quantitative real-time RT-PCR(qPCR).The protein levels of cell proliferation related protein and phosphorylated signal transducer and activator of transcription 3(STAT3)were detected by Western blotting.Results:Ppara^(Mye−/−)mice showed enhanced hepatocyte proliferation and mitosis at 32 h after PHx compared with Ppara^(fl/fl)mice,which was consistent with increased proliferating cell nuclear antigen(Pcna)mRNA and cyclinD1(CYCD1)protein levels in Ppara^(Mye−/−)mice at 32 h after PHx,indicating an accelerated liver regeneration in Ppara^(Mye−/−)mice.IHC staining showed that macrophages and neutrophils were increased in Ppara^(Mye−/−)liver at 32 h after PHx.Livers of Ppara^(Mye−/−)mice also showed an enhanced infiltration of M1 macrophages at 32 h after PHx.In vitro,Ppara-deficient bone marrow-derived macrophages(BMDMs)exhibited markedly enhanced migratory capacity and upregulated M1 genes Il6 and Tnfa but downregulated M2 gene Arg1 expressions.Furthermore,the phosphorylation of STAT3,a key transcript factor mediating IL6-promoted hepatocyte survival and proliferation,was reinforced in the liver of Ppara^(Mye−/−)mice after PHx.Conclusions:This study provides evidence that myeloid PPARαdeficiency accelerates PHx-induced liver regeneration via macrophage polarization and consequent IL-6/STAT3 activation,thus providing a potential target for manipulating liver regeneration.展开更多
Purpose: Bursal inflammation is thought to be a major cause of pain in degenerative rotator cuff tears (RCTs). While the expression of proinflammatory mediators, such as COX-2, TNF-α, IL-1β, and IL-6, is crucial for...Purpose: Bursal inflammation is thought to be a major cause of pain in degenerative rotator cuff tears (RCTs). While the expression of proinflammatory mediators, such as COX-2, TNF-α, IL-1β, and IL-6, is crucial for the pathophysiology of osteoarthritis (OA), their role in degenerative RCTs remains unknown. The aim of this study was to determine the expression of COX-2 and proinflammatory mediators in the development of RCT-induced pain by comparing their levels in patients with hip OA or RCTs. Methods: We included samples obtained from 31 shoulders of 31 patients with RCTs and samples from 30 hips of 27 patients with hip OA. The mRNA levels of COX-2, TNF-α, IL-1β, and IL-6 were determined using RT-PCR, and were compared between the subacromial bursa and hip joints. We also analyzed IL-1β-induced COX-2 expression in the subacromial bursa and synovial blast of the hip. Results: COX-2, IL-1β, and IL-6 expression levels were significantly lower in the subacromial bursa of RCTs than in hip OA samples, while no significant difference was observed for TNF-α. No significant difference in the fold increase was observed between subacromial bursa and hip OA samples, even though IL-1β-induced COX-2 expression increased in both samples. Conclusion: Our findings suggest that the main mechanism underlying pain development differs between patients with RCTs and those with hip OA.展开更多
Objective:In the present study we try to correlate between pathogenic intrinsic factor of Escherichia coli(E.coli) presented with different fimbria genotyes and biofilm formation with host immune factor entitled inter...Objective:In the present study we try to correlate between pathogenic intrinsic factor of Escherichia coli(E.coli) presented with different fimbria genotyes and biofilm formation with host immune factor entitled interleukin-6(IL-6) secretion as defense mechanism.Methods:A total of 91 pediatrics complaining of pyuria were included in the present study.In addition,20 healthy control children were included.Full microbiological study was performed for isolated E.coli.PapC alleles were studied by multiple alleles PCR and biofilm formation was studied.IL-6 was measured in urine.Results:IL-6 had statistically significant elevation in patients’urine compared to control.From biofilm study, it was found that 19 isolated E.coli had formed biofilm in vitro.Moreover,urine samples with positive biofilm formation of E.coli had statistically significant lower IL-6 secretion than those with negative E.coli for biofilms.The distribution of fimbria genotypes showed that the frequent genotype was for alleleⅠ(34.3%) followed by mixed allelesⅠandⅡ(24.1%).There was significant correlation between mixed alleles(Ⅰ&Ⅱ)and biofilm formation.Conclusion: The present study highlights the presence of significant strains of E.coli causing urinary tract infections capable of biofilm formation.Biofilm formation is associated with less innate immunity manifested by lower urinary IL- 6.The majority of isolates had fimbria genes.It appears that mixed allelesⅠandⅡhave prominent virulence effect with tendency for biofilm formation.展开更多
Chronic insomnia disorder(CID)is a relatively common clinical sleep disorder,which is es-sentially characterized by dissatisfaction with sleep due to frequent and persistent difficulties in falling asleep or maintaini...Chronic insomnia disorder(CID)is a relatively common clinical sleep disorder,which is es-sentially characterized by dissatisfaction with sleep due to frequent and persistent difficulties in falling asleep or maintaining sleep.The etiology and pathogenesis of CID are not fully understood.In the past decades,medical re-search has explored the interrelationship between cyto-kines(CKs)and sleep disorders,and this paper reviews the correlation between CID and inflammatory factors in the context of domestic and international research on the subject.展开更多
基金supported by National Natural Science Foundation of China(81370521,81670400,and 91739120)National Key R&D Program of China(2017YFC0211600)+1 种基金Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan(CIT&TCD20190332)The Key Science and Technology Project of Beijing Municipal Institutions(KZ202010025032).
文摘Background:Liver regeneration is a fundamental process for sustained body homeostasis and liver function recovery after injury.Emerging evidence demonstrates that myeloid cells play a critical role in liver regeneration by secreting cytokines and growth factors.Peroxisome proliferator-activated receptorα(PPARα),the target of clinical lipid-lowering fibrate drugs,regulates cell metabolism,proliferation,and survival.However,the role of myeloid PPARαin partial hepatectomy(PHx)-induced liver regeneration remains unknown.Methods:Myeloid-specific PPARa-deficient(Ppara^(Mye−/−))mice and the littermate controls(Ppara^(fl/fl))were subjected to sham or 2/3 PHx to induce liver regeneration.Hepatocyte proliferation and mitosis were assessed by immunohistochemical(IHC)staining for 5-bromo-2'-deoxyuridine(BrdU)and Ki67 as well as hematoxylin and eosin(H&E)staining.Macrophage and neutrophil infiltration into livers were reflected by IHC staining for galectin-3 and myeloperoxidase(MPO)as well as flow cytometry analysis.Macrophage migration ability was evaluated by transwell assay.The mRNA levels for cell cycle or inflammation-related genes were measured by quantitative real-time RT-PCR(qPCR).The protein levels of cell proliferation related protein and phosphorylated signal transducer and activator of transcription 3(STAT3)were detected by Western blotting.Results:Ppara^(Mye−/−)mice showed enhanced hepatocyte proliferation and mitosis at 32 h after PHx compared with Ppara^(fl/fl)mice,which was consistent with increased proliferating cell nuclear antigen(Pcna)mRNA and cyclinD1(CYCD1)protein levels in Ppara^(Mye−/−)mice at 32 h after PHx,indicating an accelerated liver regeneration in Ppara^(Mye−/−)mice.IHC staining showed that macrophages and neutrophils were increased in Ppara^(Mye−/−)liver at 32 h after PHx.Livers of Ppara^(Mye−/−)mice also showed an enhanced infiltration of M1 macrophages at 32 h after PHx.In vitro,Ppara-deficient bone marrow-derived macrophages(BMDMs)exhibited markedly enhanced migratory capacity and upregulated M1 genes Il6 and Tnfa but downregulated M2 gene Arg1 expressions.Furthermore,the phosphorylation of STAT3,a key transcript factor mediating IL6-promoted hepatocyte survival and proliferation,was reinforced in the liver of Ppara^(Mye−/−)mice after PHx.Conclusions:This study provides evidence that myeloid PPARαdeficiency accelerates PHx-induced liver regeneration via macrophage polarization and consequent IL-6/STAT3 activation,thus providing a potential target for manipulating liver regeneration.
文摘Purpose: Bursal inflammation is thought to be a major cause of pain in degenerative rotator cuff tears (RCTs). While the expression of proinflammatory mediators, such as COX-2, TNF-α, IL-1β, and IL-6, is crucial for the pathophysiology of osteoarthritis (OA), their role in degenerative RCTs remains unknown. The aim of this study was to determine the expression of COX-2 and proinflammatory mediators in the development of RCT-induced pain by comparing their levels in patients with hip OA or RCTs. Methods: We included samples obtained from 31 shoulders of 31 patients with RCTs and samples from 30 hips of 27 patients with hip OA. The mRNA levels of COX-2, TNF-α, IL-1β, and IL-6 were determined using RT-PCR, and were compared between the subacromial bursa and hip joints. We also analyzed IL-1β-induced COX-2 expression in the subacromial bursa and synovial blast of the hip. Results: COX-2, IL-1β, and IL-6 expression levels were significantly lower in the subacromial bursa of RCTs than in hip OA samples, while no significant difference was observed for TNF-α. No significant difference in the fold increase was observed between subacromial bursa and hip OA samples, even though IL-1β-induced COX-2 expression increased in both samples. Conclusion: Our findings suggest that the main mechanism underlying pain development differs between patients with RCTs and those with hip OA.
文摘Objective:In the present study we try to correlate between pathogenic intrinsic factor of Escherichia coli(E.coli) presented with different fimbria genotyes and biofilm formation with host immune factor entitled interleukin-6(IL-6) secretion as defense mechanism.Methods:A total of 91 pediatrics complaining of pyuria were included in the present study.In addition,20 healthy control children were included.Full microbiological study was performed for isolated E.coli.PapC alleles were studied by multiple alleles PCR and biofilm formation was studied.IL-6 was measured in urine.Results:IL-6 had statistically significant elevation in patients’urine compared to control.From biofilm study, it was found that 19 isolated E.coli had formed biofilm in vitro.Moreover,urine samples with positive biofilm formation of E.coli had statistically significant lower IL-6 secretion than those with negative E.coli for biofilms.The distribution of fimbria genotypes showed that the frequent genotype was for alleleⅠ(34.3%) followed by mixed allelesⅠandⅡ(24.1%).There was significant correlation between mixed alleles(Ⅰ&Ⅱ)and biofilm formation.Conclusion: The present study highlights the presence of significant strains of E.coli causing urinary tract infections capable of biofilm formation.Biofilm formation is associated with less innate immunity manifested by lower urinary IL- 6.The majority of isolates had fimbria genes.It appears that mixed allelesⅠandⅡhave prominent virulence effect with tendency for biofilm formation.
文摘Chronic insomnia disorder(CID)is a relatively common clinical sleep disorder,which is es-sentially characterized by dissatisfaction with sleep due to frequent and persistent difficulties in falling asleep or maintaining sleep.The etiology and pathogenesis of CID are not fully understood.In the past decades,medical re-search has explored the interrelationship between cyto-kines(CKs)and sleep disorders,and this paper reviews the correlation between CID and inflammatory factors in the context of domestic and international research on the subject.
