Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental ...Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.展开更多
Objective:To better understand the clinical phenotype of Méenière’s disease(MD),we examined family history,thyroid disorder,migraine,and associated disorders in complaints of people living with MD.Method:We...Objective:To better understand the clinical phenotype of Méenière’s disease(MD),we examined family history,thyroid disorder,migraine,and associated disorders in complaints of people living with MD.Method:We designed the study as a retrospective and examined data gathered from 912 participants with MD.Their data were originally collected by the Finnish M′eni`ere Federation(FMF).The survey data included individual case histories for environmental factors,comorbidities,disease-specific complaints,impact-related questions,cognitive complaints,health-related quality of life(HRQoL),and sense of coherence(SOC).Results:We observed significant differences between those with and without sporadic occurrence,family history,thyroid disorder,and migraine-associated complaints.Family history explained 20%of variability in patient complaints.Patients with a family history of MD whose disease started at younger age experienced balance problems,more severe vertigo spells,more severe vestibular drop attacks(VDA),and less nausea,although they had good SOC.Thyroid disorder explained 14%of variability in patient complaints.MD patients with a thyroid disorder comorbidity suffered more often from constant dizziness,balance problems,greater impact of hearing problems,cognitive complaints,and poor HRQoL.Migraine explained 12%of variability in patients’complaints and was associated with poor SOC and cognitive balance problems.MD patients with both thyroid disorder and migraine used antidepressants more often than other groups.Logistic regression analysis showed comorbidities of ischemic brain disorder(among 7.1%),kidney insufficiency(among 1.2%),and diabetes(among 7.3%)had statistically significant but restricted association with balance and gait problems,VDA,and reduced HRQoL.Conclusions:Family history of MD and thyroid disorder or migraine comorbidities in MD influence the complaint pattern and partially explain complex symptom profiles,including symptoms of cognitive problems.Confounders play a minimal role in complaint profile and impact of MD whereas comorbidities influence the complaint structure and partly explain the complex symptom profile in MD.展开更多
Since the beginning of the 21st century,major earthquakes have frequently occurred worldwide.To explore the impact of astronomical factors on earthquakes,in this study,the statistical analysis method of correlation is...Since the beginning of the 21st century,major earthquakes have frequently occurred worldwide.To explore the impact of astronomical factors on earthquakes,in this study,the statistical analysis method of correlation is used to systematically analyze the effects of astronomical factors,such as solar activity,Earth’s rotation,lunar declination angle,celestial tidal force,and other phenomena on M≥8 global earthquakes at the beginning of the 21st century.With regard to solar activity,this study focuses on the analysis of the 11-year and century cycles of solar activity.The causal relationship of the Earth’s rotation is not obvious in this work and previous works;in contrast,the valley period of the solar activity century cycle may be an important astronomical factor leading to the frequent occurrence of global earthquakes at the beginning of the 21st century.This topic warrants further study.展开更多
BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search wa...BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金supported by the National Natural Science Foundation of China,Nos.82071190 and 82371438(to LC)Innovative Strong School Project of Guangdong Medical University,No.4SG21230G(to LC)Scientific Research Foundation of Guangdong Medical University,No.GDMUM2020017(to CL)。
文摘Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.
文摘Objective:To better understand the clinical phenotype of Méenière’s disease(MD),we examined family history,thyroid disorder,migraine,and associated disorders in complaints of people living with MD.Method:We designed the study as a retrospective and examined data gathered from 912 participants with MD.Their data were originally collected by the Finnish M′eni`ere Federation(FMF).The survey data included individual case histories for environmental factors,comorbidities,disease-specific complaints,impact-related questions,cognitive complaints,health-related quality of life(HRQoL),and sense of coherence(SOC).Results:We observed significant differences between those with and without sporadic occurrence,family history,thyroid disorder,and migraine-associated complaints.Family history explained 20%of variability in patient complaints.Patients with a family history of MD whose disease started at younger age experienced balance problems,more severe vertigo spells,more severe vestibular drop attacks(VDA),and less nausea,although they had good SOC.Thyroid disorder explained 14%of variability in patient complaints.MD patients with a thyroid disorder comorbidity suffered more often from constant dizziness,balance problems,greater impact of hearing problems,cognitive complaints,and poor HRQoL.Migraine explained 12%of variability in patients’complaints and was associated with poor SOC and cognitive balance problems.MD patients with both thyroid disorder and migraine used antidepressants more often than other groups.Logistic regression analysis showed comorbidities of ischemic brain disorder(among 7.1%),kidney insufficiency(among 1.2%),and diabetes(among 7.3%)had statistically significant but restricted association with balance and gait problems,VDA,and reduced HRQoL.Conclusions:Family history of MD and thyroid disorder or migraine comorbidities in MD influence the complaint pattern and partially explain complex symptom profiles,including symptoms of cognitive problems.Confounders play a minimal role in complaint profile and impact of MD whereas comorbidities influence the complaint structure and partly explain the complex symptom profile in MD.
文摘Since the beginning of the 21st century,major earthquakes have frequently occurred worldwide.To explore the impact of astronomical factors on earthquakes,in this study,the statistical analysis method of correlation is used to systematically analyze the effects of astronomical factors,such as solar activity,Earth’s rotation,lunar declination angle,celestial tidal force,and other phenomena on M≥8 global earthquakes at the beginning of the 21st century.With regard to solar activity,this study focuses on the analysis of the 11-year and century cycles of solar activity.The causal relationship of the Earth’s rotation is not obvious in this work and previous works;in contrast,the valley period of the solar activity century cycle may be an important astronomical factor leading to the frequent occurrence of global earthquakes at the beginning of the 21st century.This topic warrants further study.
文摘BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.
