MiR-29c protects against inflammation and apoptosis in Parkinson's disease model in vivo and in vitro by targeting SP1

MicroRNAs (miRNAs) have been shown to have complicated implications in the pathogenesis of Parkinson's disease (PD). However, the role of miR-29c and the underlying mechanism in the development of PD remain not well understood. In this work, the MPTP-treated mice or MPP⁺-intoxicated SH-SY5Y cells were established as an in vivo or in vitro PD model. Then the specific agomir of miR-29c was employed to examine its biological function on PD progress. We found that miR-29c was down-expressed but SP1 was high-expressed in substantia nigra pars compacta (SNpc) of MPTP-induced PD mice. Overexpression of miR-29c attenuated dopaminergic neuron loss and α-synuclein accumulation in SNpc of PD mice. Furthermore, the increments of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and TUNEL-positive apoptotic cells in MPTP-treated mice were ameliorated by miR-29c. Similarly, in SH-SY5Y cell models of PD, we also found that miR-29c inhibited inflammatory cytokine production, reduced apoptotic rate and suppressed pro-apoptotic regulator activity. In addition, the increased expression of SP1 in PD models was found to be inhibited by miR-29c. Luciferase reporter assay confirmed that SP1 was complementary with miR-29c. Knockdown of SP1 with siRNA restored α-synuclein accumulation, inflammation and apoptosis in MPP⁺-induced SH-SY5Y cells. Collectively, this current work presents that miR-29c may directly target SP1 to protect against the neuroinflammatory and apoptotic responses in PD, providing a potential biomarker for PD diagnosis and treatment.     

Adding bovine seminal plasma prior to freezing improves post-thaw bull sperm kinematics but decreases mitochondrial activity

Variations in fertility between bulls with comparable sperm quality could be due to differences in their seminal plasma (SP). The aim of this study was to investigate the effect of adding bovine SP from bulls of known fertility to SP-free sperm samples. After removal of SP by Single Layer Centrifugation, resuspended sperm pellets were treated with SP from high or low fertility bulls at 0% (control), 1%, or 5% before freezing. Sperm quality was evaluated after thawing. Data were analyzed using Proc MIXED, SAS®. Bovine SP at 1% or 5% SP1 and SP5, respectively, decreased average path velocity, curvilinear velocity, and amplitude of lateral head displacement whereas wobble and linearity were increased. In addition, the proportion of spermatozoa with high mitochondrial membrane potential (MMP) was lowest for treatment with SP5 compared to SP1 and control. The proportion of SP did not affect other parameters of sperm quality. Thus, adding 5% bovine SP produced a favorable effect on some sperm velocity parameters but had an unfavorable effect on MMP. There were no differences in effect between SP from high and low fertility bulls.

Abbreviations: AI: artificial insemination; BCF: beat cross frequency; CASA: computer-assisted sperm analysis; IVF: in vitro fertilization; MMP: mitochondrial membrane potential; SLC: single layer centrifugation; SP: seminal plasma     

白术茯苓汤中用生白术或熟白术对湿困脾阻模型大鼠的影响

目的:研究白术茯苓汤中用生白术或熟白术对湿困脾阻模型大鼠的影响。方法:复制大鼠湿困脾阻模型。50只SD大鼠分为正常对照(等容生理盐水)组、模型(等容生理盐水)组、白术茯苓汤(生,8 g/kg)组、白术茯苓汤(熟,8 g/kg)组、平胃散(8 g/kg)组。测量大鼠体质量、腹围、腿围、平均进食量、饮水量,检测大鼠血清Na+-K+-ATP酶活性,神经降压素(NT)、P物质(SP)、血管活性肠肽(VIP)含量。结果:与正常对照组比较,模型组大鼠体质量减少,腹围、腿围增加,平均进食量、平均饮水量减少,差异有统计学意义(P<0.05);大鼠血清Na+-K+-ATP酶活性减弱,SP含量减少,NT、VIP含量增加,差异有统计学意义(P<0.05)。与模型组比较,白术茯苓汤(生)组大鼠体质量增加、腹围减少,平均进食量、平均饮水量增加,差异有统计学意义(P<0.05);大鼠血清Na+-K+-ATP酶活性增强,NT、VIP含量减少,差异有统计学意义(P<0.05)。结论:生白术之白术茯苓汤对湿困脾阻模型大鼠的保护作用较熟白术之白术茯苓汤为好,其作用机制可能是通过同时调节Na+-K+-ATP酶、NT及胃肠激素(SP、VIP)的分泌而达到治疗湿困脾阻的目的,白术茯苓汤中的生白术不可用熟白术替代。     

Hypotensive Effect of Heated Water-Based Exercise Persists After 12-Week Cessation of Training in Patients With Resistant Hypertension

Background

Heated water-based exercise (HEx) promotes a marked reduction of blood pressure (BP), but it is not entirely clear whether its effects on BP persist after cessation of HEx.

白萝卜提取物促胃动力作用中Cajal间质细胞与P物质的变化

目的探讨白萝卜提取物（raphanus sativus 1 extract，Ecr）通过Cajal间质细胞促胃肠动力作用机制。方法40只SD大鼠随机分为A（Ecr）组、B（0．9％氯化钠对照）组分别灌服等体积Ecr和0．9％氯化钠，1h后用双重免疫荧光组织化学标记的方法观察胃电起搏区Cajal间质细胞（interstitial cells of Cajal，ICC）与P物质（SP）阳性神经及产物表达的变化。结果肌间神经丛中ICC与SP阳性神经呈网络样分布，二者紧密毗邻；肌间神经丛及肌层内与ICC结合的SP阳性神经产物表达明显增加（P〈0．01）。结论白萝卜提取物的促胃肠动力作用可能与胃体ICC上结合的SP阳性神经产物表达增高有密切关系。     

New Hits as Antagonists of GPR103 Identified by HTS

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Uncomplicated oocyte donation pregnancies are associated with a higher incidence of human leukocyte antigen alloantibodies

Background

Fetuses in pregnancies conceived after oocyte donation (OD) have a higher degree of antigeneic dissimilarity with the mother compared to semi-allogeneic fetuses after natural conception. We questioned whether this leads to higher level of HLA antibody formation in OD pregnancies.

Method

Uncomplicated pregnancies after OD were compared with pregnancies conceived either spontaneously or by IVF. We calculated the number of HLA- and epitope mismatches. Maternal sera were screened for HLA antibodies with ELISA; child HLA specific antibody production was determined using CDC and Luminex with single antigen beads for class I and II.

Results

A significantly (p < 0.0001) higher incidence of HLA antibody production was observed in women conceiving after OD (69%) compared to non-donor pregnancies (24–25%). The antibody formation was positively correlated with the number of fetomaternal antigen (Spearman’s rho 0.95, p < 0.0001) and epitope mismatches (Spearman’s rho 0.91, p < 0.0001). The number of HLA-DR mismatches between women and child was an independent risk factor for the production of HLA class I specific alloantibodies.

Conclusion

Women conceiving after OD have a higher risk of developing child-specific HLA antibodies; the higher the number of immunogenetic differences, the higher the chance these antibodies are formed. The high incidence of antibody production also strongly depends upon the number of HLA-DR mismatches. Despite the stronger antibody response, OD was associated with uncomplicated pregnancy in cases included in this study.