Adrenergic β receptor activation reduces amyloid β1-42-mediated intracellular Zn2+ toxicity in dentate granule cells followed by rescuing impairment of dentate gyrus LTP

Adrenergic β receptor activation prevents human soluble amyloid β (Aβ)-induced impairment of long-term potentiation (LTP) in slices. On the basis of the evidence that human Aβ_1–42-induced impairment of LTP is due to Aβ_1–42-mediated Zn²⁺ toxicity, we postulated that adrenergic β receptor activation reduces Aβ_1–42-mediated intracellular Zn²⁺ toxicity followed by rescuing Aβ_1–42 toxicity. To test the effect of adrenergic β receptor activation, LTP was recorded at perforant pathway-dentate granule cell synapses of anesthetized rats 60 min after Aβ_1–42 injection into the dentate granule cell layer. Human Aβ_1–42-induced impairment of LTP was rescued by co-injection of isoproterenol, an adrenergic β receptor agonist, but not by co-injection of phenylephrine, an adrenergic α₁ receptor agonist. Isoproterenol did not reduce Aβ_1–42 uptake into dentate granule cells, but reduced increase in intracellular Zn²⁺ in dentate granule cells induced by Aβ_1–42. In contrast, phenylephrine did not reduce both Aβ_1–42 uptake and increase in intracellular Zn²⁺ by Aβ_1–42. In the case of human Aβ₁₋₄₀ and rat Aβ_1–42, which do not increase intracellular Zn²⁺, human Aβ₁₋₄₀- and rat Aβ_1–42-induced impairments of LTP were not rescued by co-injection of isoproterenol. The present study indicates that adrenergic β receptor activation reduces Aβ_1–42-mediated increase in intracellular Zn²⁺ in dentate granule cells, resulting in rescuing Aβ_1–42-induced impairment of LTP. It is likely that noradrenergic neuron activation by stimulating the locus coeruleus is effective for rescuing Aβ_1–42-induced cognitive decline that is caused by intracellular Zn²⁺ dysregulation in the hippocampus.     

Determinantes de la frecuentación en Atención Primaria en Cataluña

AimTo determine which variables determine the average annual attendance time per patient in Primary Care (PC) in Catalonia to improve the adequacy of the budget allocation.DesignCross-sectional ecological study.SettingThe Primary Care health centers (EAP) from the Institut Català de la Salut (ICS) in 2016.ParticipantsThe 285 EAPs from the ICS, which cover 75% of citizens over 14 years of age in Catalonia.Main measurementsAnnual average time of visits by a family doctor per patient for each EAP. It was studied how this time depended on potential explanatory variables, at the EAP level, using linear regression models.Resultsthe average visit time per patient/year was 49 minutes, varying between 23-87 minutes according to EAP. The EAPs with older population, more comorbidity, more home care, worse socioeconomic index, greater number of young pensioners and greater dispersion had more visiting time, while the EAPs with more population and more women expended less time to visit. These variables explained 64% of the visit time variability.ConclusionsThe budget allocation in PC can be based on a model that incorporates the main determinants of patient’ frequentation and adapts to their real needs. It would be necessary to deepen those factors that depend on the professional or health organizations to finish finding an optimal model of resource allocation in the PC.     

Analysis of long noncoding RNA-associated competing endogenous RNA network in glucagon-like peptide-1 receptor agonist-mediated protection in β cells

BACKGROUND Long noncoding RNAs(lncRNAs) and mRNAs are widely involved in various physiological and pathological processes. The use of glucagon-like peptide-1 receptor agonists(GLP-1 RAs) is a novel therapeutic strategy that could promote insulin secretion and decrease the rate of β-cell apoptosis in type 2 diabetes mellitus(T2 DM) patients. However, the specific lncRNAs and mRNAs and their functions in these processes have not been fully identified and elucidated.AIM To identify the lncRNAs and mRNAs that are involved in the protective effect of GLP-1 RA in β cells, and their roles.METHODS Rat gene microarray was used to screen differentially expressed(DE) lncRNAs and mRNAs in β cells treated with geniposide, a GLP-1 RA. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed to assess the underlying functions of DE mRNAs. Hub mRNAs were filtered using the STRING database and the Cytoscape plugin, CytoHubba. In order to reveal the regulatory relationship between lncRNAs and hub mRNAs, their co-expression network was constructed based on the Pearson coefficient of DE lncRNAs and mRNAs, and competing endogenous RNA(ceRNA) mechanism was explored through miRanda and TargetScan databases.RESULTS We identified 308 DE lncRNAs and 128 DE mRNAs with a fold change filter of ≥ 1.5 and P value 0.05. GO and KEGG pathway enrichment analyses indicated that the most enriched terms were G-protein coupled receptor signaling pathway, inflammatory response, calcium signaling pathway, positive regulation of cell proliferation, and ERK1 and ERK2 cascade. Pomc, Htr2 a, and Agtr1 a were screened as hub mRNAs using the STRING database and the Cytoscape plugin, CytoHubba. This result was further verified using SwissTargetPrediction tool. Through the co-expression network and competing endogenous(ceRNA) mechanism, we identified seven lncRNAs(NONRATT027738, NONRATT027888, NONRATT030038, etc.) co-expressed with the three hub mRNAs(Pomc, Htr2 a, and Agtr1 a) based on the Pearson coefficient of the expression levels. These lncRNAs regulated hub mRNA functions by competing with six miRNAs(rno-miR-5132-3 p, rno-miR-344 g, rno-miR-3075, etc.) via the ceRNA mechanism. Further analysis indicated that lncRNA NONRATT027738 interacts with all the three hub mRNAs, suggesting that it is at a core position within the ceRNA network.CONCLUSION We have identified key lncRNAs and mRNAs, and highlighted here how they interact through the ceRNA mechanism to mediate the protective effect of GLP-1 RA in β cells.     

低频电针足三里对2型糖尿病大鼠糖代谢的影响

目的研究低频电针单侧足三里对2型糖尿病(T2DM)大鼠模型糖代谢的影响,探讨低频电针足三里对T2DM大鼠的疗效机制。方法将30只8周龄雄性Wistar大鼠随机分为空白组10只和造模组20只。造模组造模后将造模成功的16只大鼠随机分为模型组8只和针刺组8只。针刺组予电针单侧足三里治疗,模型组只束缚不干预。比较3组大鼠空腹血糖(FBG)、空腹胰岛素(FI)及定量胰岛素敏感检测指数(QUICKI),观察胰岛β细胞的形态。结果 FBG治疗前与空白组比较,针刺组和模型组均有显著升高(P<0.05),针刺组与模型组比较差异无统计学意义(P>0.05);治疗后与空白组比较,针刺组和模型组均有显著升高(P<0.05),针刺组与模型组比较显著降低(P<0.05)。FI治疗前各组间比较差异均无统计学意义(P>0.05);治疗后各组间比较差异均无统计学意义(P>0.05)。QUICKI治疗前与空白组比较,针刺组和模型组均降低(P<0.05),针刺组与模型组比较差异无统计学意义(P>0.05);治疗后针刺组与空白组比较差异无统计学意义(P>0.05),模型组较空白组降低(P<0.05),针刺组较模型组升高(P<0.05)。在光镜下,针刺组胰腺组织分布均匀度与空白组接近,胰岛结构比较完整,细胞密度略低于空白组,胰岛β细胞胞浆见少量肿胀,纤维组织稍有增生。结论电针足三里能有效控制高糖高脂饮食联合链脲佐菌素(STZ)诱导的T2DM大鼠模型的病情发展,改善胰岛素敏感度及胰岛β细胞的形态。     

健脾益气方对初诊2型糖尿病患者胰岛β细胞功能的影响

目的：观察健脾益气方对初诊2型糖尿病患者胰岛β细胞功能的影响。方法：90例初诊脾虚型2型糖尿病患者随机分为观察组及对照组,各45例。对照组给予糖尿病教育、饮食、运动治疗及胰岛素强化治疗,观察组患者对照组基础上给予健脾益气方,随访3个月。比较治疗后1个月、3个月两组患者血糖水平、糖化血红蛋白（ haemoglobin A1c,HbAlc）含量、胰岛素、C肽含量、胰岛素分泌指数（ homeostasis model assessment-B,Homa-β）、胰岛素抵抗指数（ Insulin resistance index,IRI）、脾虚证候积分。结果：观察组患者血糖水平、HbAlc、C肽改善优于对照组,两组比较,差异有统计学意义（ P<0.05）。观察组Homa-β升高、IRI降低明显,与对照组比较,差异有统计学意义（ P<0.05）。观察组脾虚证候积分改善明显,与对照组患者比较,差异有统计学意义（ P<0.05）。结论：健脾益气方对糖尿病患者胰岛β细胞具有一定程度的调节作用,能改善患者脾虚证候,效果满意。     

β-hCG、TGF-β和TβR-Ⅰ在卵巢上皮性癌中的表达及意义

目的:探讨人绒毛膜促性腺激素β亚单位(β-hCG)、转化生长因子β亚单位(TGF-β)及转化生长因子β亚单位受体Ⅰ (TβR-Ⅰ)在卵巢上皮性癌中的表达及临床意义.方法:选取2008年1月～2014年1月在石河子大学医学院第一附属医院以手术切除为初次治疗的卵巢上皮性癌石蜡标本60例、卵巢良性肿瘤组织标本40例和正常卵巢组织20例,采用免疫组化法检测β-hCG、TGF-β及TβR-Ⅰ的表达情况.结果:与卵巢良性肿瘤组织和正常卵巢组织相比,卵巢上皮性癌组织中β-hCG、TGF-β和TβR-Ⅰ的阳性表达率均明显升高,差异有统计学意义(P＜0.05);卵巢上皮性癌组织中β-hCG的阳性表达率与其手术病理分期及病理类型密切相关(P＜0.05),而TβR-Ⅰ及TGF-β的阳性表达率与病理类型密切相关(P＜0.05);β-hCG与TGF-β及TβR-Ⅰ的阳性表达率均呈负相关(r=-0.568,P＜0.01;r=-0.673,P＜0.01),TGF-β与TβR-Ⅰ的阳性表达率无相关性(r=0.128,P＞0.01).结论:β-hCG、TGF-β和TβR-Ⅰ对卵巢良性肿瘤和卵巢上皮性癌的鉴别诊断具有一定的临床意义.     

血清25(OH)D3与胰岛β细胞功能和胰岛素抵抗的关系

目的 分析血清25-羟维生素D3与胰岛β细胞功能和胰岛素抵抗的关系.方法 选取2012年7月至2014年7月收治的确诊为2型糖尿病的患者共100例,同时选取同期体检的健康人100例作为正常对照组.对比两组的性别、年龄、血压、脂谱、血糖、血清25(OH)D3水平等.测定所有入组者的胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(HOMA-IS)和胰岛β细胞功能指数(HOMA-B),分析血清25(OH)D3水平和三组指数之间的相关性.结果 糖尿病组的SBP、FPG、2hPG、HbA1c、TG和LDL-C显著高于正常组,25(OH)D3和HDL-C显著低于正常组,P均＜0.01.血清25(OH)D3和HOMA-B及HOMA-IS之间存在正相关,r值分别为0.413和0.229,P＜0.05;血清25(OH)D3和HOMA-IR之间存在负相关,r=-0.236,P＜0.05;回归方程分别为HOMA-B=0.413×VD+0.432,HOMA-IS=0.229×VD+0.238,HOMA-IR=-0.236×VD+0.527.结论 2型糖尿病患者血清25(OH)D3水平较低,可能与其胰岛β细胞功能下降和胰岛素抵抗有关,对于2型糖尿病患者可适当补充维生素D.     

胰岛β细胞功能检测及评价方法的新进展

胰岛β细胞的胰岛素分泌缺陷和(或)靶组织对胰岛素敏感性降低是糖尿病的重要病理生理机制,早期检测及评估胰岛β细胞功能,对于病情评估、早期干预及疾病预后有重要意义。目前,对其检测及评价的方法主要包括：胰岛β细胞功能的评估指数、胰岛素脉冲式分泌功能检测、葡萄糖刺激及非糖物质刺激的胰岛素分泌功能的检测、β细胞分泌其他物质的功能检测。其中,近年来在由检测C肽来评估β细胞功能的方面取得了一些进展,包括混合餐耐受性试验90 min C 肽检测、尿C肽/肌酐比值检测。     

When astrocytes become harmful: Functional and inflammatory responses that contribute to Alzheimer's disease

A growing body of research suggests that astrocytes play roles as contributors to the pathophysiology of Alzheimer's disease (AD). Several lines of evidence propose that activated astrocytes produce and release proinflammatory molecules that may be critical for the generation of amyloid-β peptide (Aβ). However, accumulating evidence indicates that Aβ may activate astrocytes, which leads to an increase in cytokines that has been suggested to be a causative factor in the cognitive dysfunction of AD; thus, a vicious circle may be created. Intrinsic inflammatory mechanisms may provide a regulatory system that is capable of influencing the neuronal microenvironment that affects neuronal survival. In this article, we address the evidence surrounding the interactions of dysfunctional astrocytes with neighboring neurons that may initiate a cascade of events that culminates with neuronal injury and the expression of the hallmark lesions of AD. Comprehensive knowledge of the molecular mechanisms underlying the participation of astrocytes in neurodegeneration could aid the development of therapies to restore proper astrocyte function that can be used in AD patients to prevent or alleviate the progression of the disease in a more efficient and comprehensive manner.