In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain r...In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-23 （p19/p40） and IL-12 （p35/p40）. The results showed that the expression of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic non-lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, nonesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL- 12.展开更多
Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in ...Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.展开更多
AIM To evaluate the impact of cytochrome P450 2C19(CYP2C19) and interleukin-1β(IL-1β) polymorphisms on the efficacy of Helicobacter pylori(H. pylori) eradication by using rabeprazole-based hybrid therapy.METHODS A t...AIM To evaluate the impact of cytochrome P450 2C19(CYP2C19) and interleukin-1β(IL-1β) polymorphisms on the efficacy of Helicobacter pylori(H. pylori) eradication by using rabeprazole-based hybrid therapy.METHODS A total of 88 H. pylori-infected patients were recruited to receive 14-d of hybrid therapy from March 2013 to May 2014. Three patients were excluded from analysis because of incomplete compliance. Either a follow-up endoscopy or 13 C-urea test was performed to determine the results of H. pylori eradication therapy. The genotypes of CYP2C19 and IL-1β were analyzed to investigate the impact on treatment effect. RESULTS The total eradication rate of H. pylori was 92.94%(79/85). According to the CYP2C19 genotypes, the rates of H. pylori eradication were 89.19% in extensive metabolizers(EM) and 95.83% in non-EM. The H.pylori eradication rates regarding the IL-1β genotypes were 92.59% in the normal acid secretion group and 93.10% in the low acid secretion group. After multivariable logistic regression analysis, both the genotypes of CYP2C19 and IL-1β had no significant influences on the eradication rates of H. pylori.CONCLUSION The CYP2C19 and IL-1β polymorphisms are not significantly independent factors of H.pylori eradication using rabeprazole-based hybrid therapy.展开更多
Proton nuclear(^(1)H)is the observed nucleus on which most magnetic resonance imaging(MRI)applications depend.Most traditional^(1)H MRI can provide structural and functional information about organisms,while various n...Proton nuclear(^(1)H)is the observed nucleus on which most magnetic resonance imaging(MRI)applications depend.Most traditional^(1)H MRI can provide structural and functional information about organisms,while various non-proton nuclei(X-nuclei)MRI can provide more metabolic information.However,due to the relatively poor signal-to-noise ratio(SNR)of X-nuclei MRI,their applications are quite rare compared to^(1)H.Benefit from the rapid developments of MRI hardware and software technologies,X-nuclei MRI has recently attracted increasing interests in biomedical research.This review firstly introduces some current methods to improve the SNR of X-nuclei MRI.Secondly,this review describes biomedical applications of X-nuclei MRI,especially focusing on the current use of X-nuclei(^(13)C,^(17)O,^(19)F,^(23)Na and^(31)P)MRI to study related diseases in different organs,including the brain,liver,kidney,heart and bone.Finally,perspectives studies on X-nuclei imaging and its potential applications are described in biomedical research.展开更多
In order to investigate the role of Th17 cytokines in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-17, IL-23 (p19/p40), and IL-6 in sk...In order to investigate the role of Th17 cytokines in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-17, IL-23 (p19/p40), and IL-6 in skin lesions and non-lesions of the patients with psoriasis and skin tissues of normal subjects. The results showed that the mRNA expression levels of IL-17, IL-23p19, IL-23p40 and IL-6 in psoriasis leision were significantly higher than those of non-leisions (1.231±0.843 vs 1.003±0.044, 1.166±0.142 vs 0.765±0.133, 1.125±0.104 vs 0.730±0.103, 1.186±0.222 vs 0.976±0.122, respectively, all P<0.05). Meanwhile, The expression levels of IL-17 mRNA, IL-23p19 mRNA, IL-23p40 mRNA and IL-6 mRNA were higher in non-leisions than those in normal skin tissues (1.003±0.044 vs 0.620±0.104, 0.765±0.133 vs 0.584±0.078, 0.730±0.103 vs 0.000 ±0.000, 0.976±0.122 vs 0.656±0.121, respectively, all P<0.05). The overexpression of Th17 cy- tokines in the skin lesions of patients with psoriasis may indicate that Th17 cytokines play a very important role in the immunopathogenesis of psoriasis.展开更多
Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC ...Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.展开更多
While there is mounting evidence that interleukin （IL）-23-IL-17 axis plays a critical role in the pathogenesis of various autoimmune diseases, much remains to be elucidated on how IL-23 is induced in the pathologica...While there is mounting evidence that interleukin （IL）-23-IL-17 axis plays a critical role in the pathogenesis of various autoimmune diseases, much remains to be elucidated on how IL-23 is induced in the pathological processes. IL-23 is a heterodimer composed of p19 and p40, the latter being shared with IL-12. We previously reported that prostaglandin （PG） E2 promotes CD40-mediated induction of 1123a （p19） expression through its E receptor subtype 4 （EP4） receptor in splenic dendritic cells （DCs）. Here, we have analyzed signaling pathways regulating 1123a induction in the cross talk between EP4 and CD40 in bone marrow-derived DCs. We found that PGE2 synergistically induced 1123a transcription with CD40 signaling. An EP4 agonist, but not agonists of EP1, EP2, or EP3, reproduced this action. Stimulation of CD40 with an agonist antibody evoked biphasic induction of 1123a expression, with the early phase peaking at 1 h and the late phase peaking at 12 h and lasting up to 36 h after stimulation, whereas induction by lipopolysaccharide or tumor necrosis factor-α was transient. The early phase induction by CD40 stimulation was absent in DCs derived from Nfkbl-deficient mice, and the late phase induction was eliminated by RNA interference of nuclear factor-kappa B （NF-κB） p100 subunit. Further, cAMP response element-binding protein （CREB） depletion completely eliminated the induction of 1123a by CD40 stimulation. The addition of the EP4 agonist amplified the induction in both phases through the cAMP-protein kinase A （PKA） pathway. These results suggest that 1123a expression in DCs is synergistically triggered by the PG E2-EP4-cAMP-PKA pathway and canonical/non-canonical NF-KB pathways and CREB activated by CD40 stimulation.展开更多
文摘In order to investigate the mRNA expression and function of interleukin-23 （p 19/p40） and interleukin-12 （p35/p40） in the psoriatic lesion, no-lesion and normal human skin, reverse transcriptase-polymerase chain reaction （RT-PCR） was used to detect the expression of IL-23 （p19/p40） and IL-12 （p35/p40）. The results showed that the expression of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic lesion than those of non-lesional skin and normal skin. The levels of IL-23p19 mRNA and p40 （IL-12/IL-23） mRNA were higher in psoriatic non-lesional skin than normal skin. However, no significant difference was found in the level of IL-12p35 mRNA among the psoriatic lesional skin, nonesional skin and normal skin. It was suggested that IL-23 might be more important in the pathogenesis of psoriasis than IL- 12.
基金supported by the Youth Development Project of Air Force Military Medical University,No.21 QNPY072Key Project of Shaanxi Provincial Natural Science Basic Research Program,No.2023-JC-ZD-48(both to FF)。
文摘Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.
文摘AIM To evaluate the impact of cytochrome P450 2C19(CYP2C19) and interleukin-1β(IL-1β) polymorphisms on the efficacy of Helicobacter pylori(H. pylori) eradication by using rabeprazole-based hybrid therapy.METHODS A total of 88 H. pylori-infected patients were recruited to receive 14-d of hybrid therapy from March 2013 to May 2014. Three patients were excluded from analysis because of incomplete compliance. Either a follow-up endoscopy or 13 C-urea test was performed to determine the results of H. pylori eradication therapy. The genotypes of CYP2C19 and IL-1β were analyzed to investigate the impact on treatment effect. RESULTS The total eradication rate of H. pylori was 92.94%(79/85). According to the CYP2C19 genotypes, the rates of H. pylori eradication were 89.19% in extensive metabolizers(EM) and 95.83% in non-EM. The H.pylori eradication rates regarding the IL-1β genotypes were 92.59% in the normal acid secretion group and 93.10% in the low acid secretion group. After multivariable logistic regression analysis, both the genotypes of CYP2C19 and IL-1β had no significant influences on the eradication rates of H. pylori.CONCLUSION The CYP2C19 and IL-1β polymorphisms are not significantly independent factors of H.pylori eradication using rabeprazole-based hybrid therapy.
基金supported by Chinese Academy of Sciences MRI Technology Alliance under Grant 2020GZ1003.
文摘Proton nuclear(^(1)H)is the observed nucleus on which most magnetic resonance imaging(MRI)applications depend.Most traditional^(1)H MRI can provide structural and functional information about organisms,while various non-proton nuclei(X-nuclei)MRI can provide more metabolic information.However,due to the relatively poor signal-to-noise ratio(SNR)of X-nuclei MRI,their applications are quite rare compared to^(1)H.Benefit from the rapid developments of MRI hardware and software technologies,X-nuclei MRI has recently attracted increasing interests in biomedical research.This review firstly introduces some current methods to improve the SNR of X-nuclei MRI.Secondly,this review describes biomedical applications of X-nuclei MRI,especially focusing on the current use of X-nuclei(^(13)C,^(17)O,^(19)F,^(23)Na and^(31)P)MRI to study related diseases in different organs,including the brain,liver,kidney,heart and bone.Finally,perspectives studies on X-nuclei imaging and its potential applications are described in biomedical research.
文摘In order to investigate the role of Th17 cytokines in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-17, IL-23 (p19/p40), and IL-6 in skin lesions and non-lesions of the patients with psoriasis and skin tissues of normal subjects. The results showed that the mRNA expression levels of IL-17, IL-23p19, IL-23p40 and IL-6 in psoriasis leision were significantly higher than those of non-leisions (1.231±0.843 vs 1.003±0.044, 1.166±0.142 vs 0.765±0.133, 1.125±0.104 vs 0.730±0.103, 1.186±0.222 vs 0.976±0.122, respectively, all P<0.05). Meanwhile, The expression levels of IL-17 mRNA, IL-23p19 mRNA, IL-23p40 mRNA and IL-6 mRNA were higher in non-leisions than those in normal skin tissues (1.003±0.044 vs 0.620±0.104, 0.765±0.133 vs 0.584±0.078, 0.730±0.103 vs 0.000 ±0.000, 0.976±0.122 vs 0.656±0.121, respectively, all P<0.05). The overexpression of Th17 cy- tokines in the skin lesions of patients with psoriasis may indicate that Th17 cytokines play a very important role in the immunopathogenesis of psoriasis.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT and Future Planning(NRF-2017R1A2B4005915)
文摘Objective: To evaluate effects of docosahexaenoic acid-enriched phosphatidylcholine(DHAPC) on cytokine production induced by lipopolysaccharide(LPS). Methods: The culture supernatants of splenocytes exposed to DHA-PC along with LPS were harvested to determine the production of Th 1(IFN-kines. Cytokines were m毭 and IL-2) and Th2 [IL-4, IL-5, IL-6 and IL-12/IL-23(p40)] cytoeasured using ELISA. Results: Co-administration of DHAPC with LPS resulted in significantly lower IL-2 expression compared to that observed with administration of only LPS(P<0.01). Treatment with DHA-PC and LPS significantly increased IL-5 expression(P<0.01). Moreover, co-administration of DHA-PC with LPS significantly decreased IL-6 and IL-12/IL-23(p40) expressions compared to that observed with administration of only LPS(P<0.01). Conclusions: Our results suggest that DHA-PC inhibits pro-inflammatory cytokines [IL-2, IL-6 and IL-12/IL-23(p40)] expression on induction of inflammation.
文摘While there is mounting evidence that interleukin （IL）-23-IL-17 axis plays a critical role in the pathogenesis of various autoimmune diseases, much remains to be elucidated on how IL-23 is induced in the pathological processes. IL-23 is a heterodimer composed of p19 and p40, the latter being shared with IL-12. We previously reported that prostaglandin （PG） E2 promotes CD40-mediated induction of 1123a （p19） expression through its E receptor subtype 4 （EP4） receptor in splenic dendritic cells （DCs）. Here, we have analyzed signaling pathways regulating 1123a induction in the cross talk between EP4 and CD40 in bone marrow-derived DCs. We found that PGE2 synergistically induced 1123a transcription with CD40 signaling. An EP4 agonist, but not agonists of EP1, EP2, or EP3, reproduced this action. Stimulation of CD40 with an agonist antibody evoked biphasic induction of 1123a expression, with the early phase peaking at 1 h and the late phase peaking at 12 h and lasting up to 36 h after stimulation, whereas induction by lipopolysaccharide or tumor necrosis factor-α was transient. The early phase induction by CD40 stimulation was absent in DCs derived from Nfkbl-deficient mice, and the late phase induction was eliminated by RNA interference of nuclear factor-kappa B （NF-κB） p100 subunit. Further, cAMP response element-binding protein （CREB） depletion completely eliminated the induction of 1123a by CD40 stimulation. The addition of the EP4 agonist amplified the induction in both phases through the cAMP-protein kinase A （PKA） pathway. These results suggest that 1123a expression in DCs is synergistically triggered by the PG E2-EP4-cAMP-PKA pathway and canonical/non-canonical NF-KB pathways and CREB activated by CD40 stimulation.
