An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the pres...Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.展开更多
AIM: Interleukin 8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is ...AIM: Interleukin 8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about the two distinct receptors, CXC receptor (CXCR)-1 and -2.The purpose of this study was to determine CXCR-1 and -2 messenger RNA expression levels in RE.METHODS: We studied 26 patients with RE and 15asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of CXCR-1 and -2 mRNA levels by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and another was formalin-fixed for histopathological evaluation.We also examined the association of the expression levels of CXCR-1 and -2 mRNA with histopathological hallmarks of RE.RESULTS: The relative CXCR-1 and -2 mRNA expression levels were rather decreased in esophageal mucosa of patients with RE, compared to those in normal esophagus of controls. There were no significant difference in the relative mRNA expression levels of CXCR-1 and -2 among endoscopic grades of RE based on the Los Angeles classification. Each histopathological hallmark of GERD was not associated with the expression levels of CXCR-1 and -2 mRNA.CONCLUSION: Apart from overexpression of IL-8, the relative expression levels of CXCR-1 and -2 mRNA were rather lower than expected in the affected esophageal mucosa of patients with RE.展开更多
目的 通过研究腺苷、白介素 (IL ) - 1、茶碱对哮喘患者外周血单个核细胞 (PBMCs)表达 A2 a及A2 b腺苷受体 (A2 a AR及 A2 b AR) m RNA的影响 ,探讨 A2 a AR及 A2 b AR在哮喘发病中的作用 ,为临床使用茶碱提供理论依据。方法 11例正...目的 通过研究腺苷、白介素 (IL ) - 1、茶碱对哮喘患者外周血单个核细胞 (PBMCs)表达 A2 a及A2 b腺苷受体 (A2 a AR及 A2 b AR) m RNA的影响 ,探讨 A2 a AR及 A2 b AR在哮喘发病中的作用 ,为临床使用茶碱提供理论依据。方法 11例正常人及哮喘患者 PBMCs经 Ficoll液分离 ,分对照组、腺苷组、腺苷 +IL- 1组及腺苷 +茶碱4组 ,体外培养 18小时 ,收集细胞 ,采用逆转录 -聚合酶链反应 (RT- PCR)法和图象分析半定量法检测 A2 a AR及 A2 bAR m RNA表达。结果 正常人及哮喘患者各组 PBMCs表达 A2 a AR m RNA无明显差异 (P>0 .0 5 )。哮喘患者PBMCs A2 b AR m RNA表达较正常人增加 (P<0 .0 1) ;腺苷、IL- 1促进哮喘患者 PBMCs表达 A2 b AR m RNA(P<0 .0 5 ) ;茶碱对正常人及哮喘患者 PBMCs表达 A2 b AR m RNA均有抑制作用 (P<0 .0 1)。腺苷及 IL- 1对哮喘患者PBMCs A2 b AR m RNA表达的影响与血清 TIg E水平呈正相关 (P<0 .0 5 ) ,与 FEV1%呈负相关 P<0 .0 5 )。结论 哮喘患者 PBMCs表达 A2 b AR m RNA增加 ,腺苷及 IL- 1促进其表达 ,且与患者机体过敏状态及气道阻塞程度相关 ,茶碱能抑制 A2 b AR m RNA表达 ;腺苷、IL- 1及茶碱对 PBMCs表达 A2 a AR m展开更多
目的探讨血清可溶性白细胞介素-2受体(sIL-2R)、降钙素原、微小RNA(miR)-223与新生儿肺炎病情程度及转归的关系。方法回顾性选取2018年1月至2023年6月池州市第二人民医院新生儿科收治的80例新生儿肺炎患儿作为肺炎组,另外选取本院同期...目的探讨血清可溶性白细胞介素-2受体(sIL-2R)、降钙素原、微小RNA(miR)-223与新生儿肺炎病情程度及转归的关系。方法回顾性选取2018年1月至2023年6月池州市第二人民医院新生儿科收治的80例新生儿肺炎患儿作为肺炎组,另外选取本院同期出生的健康新生儿80名作为对照组。对比两组的血清sIL-2R、降钙素原、miR-223水平。并按照患儿病情程度、治疗转归进行分组,其中,轻度组患儿44例,重度组患儿36例;经过治疗,预后良好组患儿63例,预后不良组患儿17例。对比不同病情程度、不同转归新生儿肺炎患儿血清sIL-2R、降钙素原、miR-223水平。采用多因素Logistic回归模型分析血清sIL-2R、降钙素原、miR-223与患儿治疗转归结局的关系。结果肺炎组患儿血清sIL-2R、降钙素原、miR-223水平分别为(32.40±8.94)μg/mL、(10.40±2.91)ng/mL、9.84±2.77,均显著高于对照组[(15.48±3.84)μg/mL、(5.84±1.50)ng/mL、6.10±1.84],差异均有统计学意义(P<0.05)。重度组患儿的血清sIL-2R、降钙素原、miR-223水平分别为(36.63±8.70)μg/mL、(12.44±2.70)ng/mL、11.65±2.32,均显著高于轻度组[(28.94±6.13)μg/mL、(8.73±2.65)ng/mL、8.36±2.45],差异均有统计学意义(P<0.05)。预后不良组患儿的血清sIL-2R、降钙素原、miR-223水平分别为(40.85±6.92)μg/mL、(15.70±2.56)ng/mL、15.10±2.13,均显著高于预后良好组[(30.12±8.77)μg/mL、(8.97±2.43)ng/mL、8.42±2.65],差异均有统计学意义(P<0.05)。不同分娩孕周(≥37周vs.<37周)、不同出生体重(≥2500 g vs.<2500 g)、不同出生1 min Apgar评分(≥8分vs.<8分)的新生儿肺炎患儿的转归结局比较,差异均有统计学意义(P<0.05);Logistic回归模型分析,结果显示:分娩孕周<37周、出生体重<2500 g、出生1 min Apgar评分<8分及血清sIL-2R升高、降钙素原升高、miR-223升高是新生儿肺炎患儿治疗转归结局不良的独立危险因素(P<0.05)。结论新生儿肺炎患儿血清sIL-2R、降钙素原、miR-223水平显著提高,并且与患儿病情程度、不良预后结局关系密切。展开更多
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
文摘Type 1 diabetes can be classified into immune-mediated diabetes (type 1A) and idiopathic diabetes, which lacks immunological evidence for beta cell autoimmunity (type 1B). Type 1A diabetes is characterized by the presence of the anti-glutamic acid decarboxylase antibody (anti-GADab). Fulminant type 1 diabetes is classified as type 1B diabetes, and characterized by the absence of anti-GADab, flu-like symptoms, and elevated serum exocrine pancreatic enzymes. We report a type 1 diabetic patient who showed flu-like symptoms, elevated serum exocrine pancreatic enzymes, and an extremely high-titer of anti-GADab, manifesting the characteristics of both type 1A and fulminant type 1 diabetes.
文摘AIM: Interleukin 8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about the two distinct receptors, CXC receptor (CXCR)-1 and -2.The purpose of this study was to determine CXCR-1 and -2 messenger RNA expression levels in RE.METHODS: We studied 26 patients with RE and 15asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of CXCR-1 and -2 mRNA levels by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), and another was formalin-fixed for histopathological evaluation.We also examined the association of the expression levels of CXCR-1 and -2 mRNA with histopathological hallmarks of RE.RESULTS: The relative CXCR-1 and -2 mRNA expression levels were rather decreased in esophageal mucosa of patients with RE, compared to those in normal esophagus of controls. There were no significant difference in the relative mRNA expression levels of CXCR-1 and -2 among endoscopic grades of RE based on the Los Angeles classification. Each histopathological hallmark of GERD was not associated with the expression levels of CXCR-1 and -2 mRNA.CONCLUSION: Apart from overexpression of IL-8, the relative expression levels of CXCR-1 and -2 mRNA were rather lower than expected in the affected esophageal mucosa of patients with RE.
文摘目的 通过研究腺苷、白介素 (IL ) - 1、茶碱对哮喘患者外周血单个核细胞 (PBMCs)表达 A2 a及A2 b腺苷受体 (A2 a AR及 A2 b AR) m RNA的影响 ,探讨 A2 a AR及 A2 b AR在哮喘发病中的作用 ,为临床使用茶碱提供理论依据。方法 11例正常人及哮喘患者 PBMCs经 Ficoll液分离 ,分对照组、腺苷组、腺苷 +IL- 1组及腺苷 +茶碱4组 ,体外培养 18小时 ,收集细胞 ,采用逆转录 -聚合酶链反应 (RT- PCR)法和图象分析半定量法检测 A2 a AR及 A2 bAR m RNA表达。结果 正常人及哮喘患者各组 PBMCs表达 A2 a AR m RNA无明显差异 (P>0 .0 5 )。哮喘患者PBMCs A2 b AR m RNA表达较正常人增加 (P<0 .0 1) ;腺苷、IL- 1促进哮喘患者 PBMCs表达 A2 b AR m RNA(P<0 .0 5 ) ;茶碱对正常人及哮喘患者 PBMCs表达 A2 b AR m RNA均有抑制作用 (P<0 .0 1)。腺苷及 IL- 1对哮喘患者PBMCs A2 b AR m RNA表达的影响与血清 TIg E水平呈正相关 (P<0 .0 5 ) ,与 FEV1%呈负相关 P<0 .0 5 )。结论 哮喘患者 PBMCs表达 A2 b AR m RNA增加 ,腺苷及 IL- 1促进其表达 ,且与患者机体过敏状态及气道阻塞程度相关 ,茶碱能抑制 A2 b AR m RNA表达 ;腺苷、IL- 1及茶碱对 PBMCs表达 A2 a AR m
文摘目的探讨血清可溶性白细胞介素-2受体(sIL-2R)、降钙素原、微小RNA(miR)-223与新生儿肺炎病情程度及转归的关系。方法回顾性选取2018年1月至2023年6月池州市第二人民医院新生儿科收治的80例新生儿肺炎患儿作为肺炎组,另外选取本院同期出生的健康新生儿80名作为对照组。对比两组的血清sIL-2R、降钙素原、miR-223水平。并按照患儿病情程度、治疗转归进行分组,其中,轻度组患儿44例,重度组患儿36例;经过治疗,预后良好组患儿63例,预后不良组患儿17例。对比不同病情程度、不同转归新生儿肺炎患儿血清sIL-2R、降钙素原、miR-223水平。采用多因素Logistic回归模型分析血清sIL-2R、降钙素原、miR-223与患儿治疗转归结局的关系。结果肺炎组患儿血清sIL-2R、降钙素原、miR-223水平分别为(32.40±8.94)μg/mL、(10.40±2.91)ng/mL、9.84±2.77,均显著高于对照组[(15.48±3.84)μg/mL、(5.84±1.50)ng/mL、6.10±1.84],差异均有统计学意义(P<0.05)。重度组患儿的血清sIL-2R、降钙素原、miR-223水平分别为(36.63±8.70)μg/mL、(12.44±2.70)ng/mL、11.65±2.32,均显著高于轻度组[(28.94±6.13)μg/mL、(8.73±2.65)ng/mL、8.36±2.45],差异均有统计学意义(P<0.05)。预后不良组患儿的血清sIL-2R、降钙素原、miR-223水平分别为(40.85±6.92)μg/mL、(15.70±2.56)ng/mL、15.10±2.13,均显著高于预后良好组[(30.12±8.77)μg/mL、(8.97±2.43)ng/mL、8.42±2.65],差异均有统计学意义(P<0.05)。不同分娩孕周(≥37周vs.<37周)、不同出生体重(≥2500 g vs.<2500 g)、不同出生1 min Apgar评分(≥8分vs.<8分)的新生儿肺炎患儿的转归结局比较,差异均有统计学意义(P<0.05);Logistic回归模型分析,结果显示:分娩孕周<37周、出生体重<2500 g、出生1 min Apgar评分<8分及血清sIL-2R升高、降钙素原升高、miR-223升高是新生儿肺炎患儿治疗转归结局不良的独立危险因素(P<0.05)。结论新生儿肺炎患儿血清sIL-2R、降钙素原、miR-223水平显著提高,并且与患儿病情程度、不良预后结局关系密切。
