Type 2 diabetes mellitus augments Parkinson’s disease risk or the other way around: Facts,challenges and future possibilities

About 10% of the adult population is living with type 2 diabetes mellitus (T2DM) and 1% of the population over 60 years of age is suffering from Parkinson’s disease (PD). A school of thought firmly believes that T2DM, an age-related disease, augments PD risk. Such relationship is reflected from the severity of PD symptoms in drug naive subjects possessing T2DM. Onset of Parkinsonian feature in case controls possessing T2DM corroborates the role of hyperglycemia in PD. A few cohort, meta-analysis and animal studies have shown an increased PD risk owing to insulin resistance. High fat diet and role of insulin signaling in the regulation of sugar metabolism, oxidative stress, α-synuclein aggregation and accumulation, inflammatory response and mitochondrial function in PD models and sporadic PD further connect the two. Although little is reported about the implication of PD in hyperglycemia and T2DM, a few studies have also contradicted. Ameliorative effect of anti-diabetic drugs on Parkinsonian symptoms and vague outcome of anti-PD medications in T2DM patients also suggest a link. The article reviews the literature supporting augmented risk of one by the other, analysis of proof of the concept, facts, challenges, future possibilities and standpoint on the subject.     

绿原酸及其肠道代谢产物对中枢神经系统疾病的作用和机制研究进展

绿原酸具有抗菌、抗病毒、清除自由基和兴奋中枢神经系统等多种生物活性。然而绿原酸仅有约1/3直接吸收入体内,其生物活性更多地是依靠其肠道代谢产物发挥效应得以实现。因此,研究绿原酸对中枢神经系统疾病的作用,有必要结合其肠道代谢产物的相关活性。该文结合近年来关于绿原酸的肠道代谢研究结果,综述了绿原酸及肠道代谢产物对于中枢神经系统疾病的潜在作用和作用机制,为进一步提高其应用价值提供依据。     

Evaluation of anaphylactoid constituents in vitro and in vivo

Natural medicine injections have been widely used in clinics, while adverse reaction reports also have increased rapidly in recent years. To examine the anaphylactoid constituents of natural medicine injections, RBL-2H3 cell degranulation and human serum complement activation models were used to screen the anaphylactoid constituents, and the BN rat model was used to explore the anaphylactoid mechanism of these constituents. The result of an in vitro study showed that the individual compounds of natural medicine injections (chlorogenic acid, hyodeoxycholic acid, cholalic acid, ginkgolic acid, phillyrin, schisandrin B, schisandrin A, puerarin, and tanshinone IIA) and polysaccharide could not induce RBL-2H3 to release histamine and β-hexosaminidase, while proteins Tween-80 and tannic acid were the main anaphylactoid constituents in the natural medicine injections. The in vivo study also indicated that > 10 kDa molecules (proteins) activated classical complement pathways through direct stimulation to cause an anaphylactoid reaction. Tween-80 activated direct stimulation and coagulation pathways through classical and alternative pathways; tannic acid induced anaphylactoid reaction through co-activation of the kallikrein-kinin system, coagulation, integrated, classical and alternative complement pathways. This is the first study to evaluate the anaphylactoid constituents systematically through in vitro and in vivo study. And tannic acid, > 10 kDa molecules (proteins), and injection additives such as Tween-80 are the main anaphylactoid constituents of natural medicine injections.     

TNNT1 myopathy with novel compound heterozygous mutations

Nemaline myopathies are clinically and genetically heterogeneous disorders caused by several different genes. One of them is TNNT1, which was initially described in Amish families and has not been reported in Asian populations. Although most TNNT1 myopathies are caused by loss-of-function mutations, several recent studies have shown that missense mutations can also be pathogenic. A 16-year-old Korean boy with progressive muscle weakness visited the Seoul National University Hospital. He showed generalized myopathy, which was predominant in the paraspinal and neck muscles. Moreover, nemaline rods were observed in a muscle biopsy. Whole-exome sequencing of DNA samples of the patient and his younger brother, who had a similar phenotype, revealed novel compound heterozygous mutations in TNNT1 (c.724G>C (p.Ala242Pro) and c.611+1G>A). Sanger sequencing of cDNA extracted from muscle samples of the patient confirmed partial or total skipping of exon 11 in the splicing variant. The impact of the missense variant on muscle integrity and locomotor activity was verified using a zebrafish loss-of-function model. Here, we reported novel familial cases of TNNT1 myopathy with intermediate clinical presentations caused by compound heterozygous mutations and demonstrated their functional defects using an animal model.     

MK-801急性处理改变斑马鱼幼鱼自发运动和焦虑行为

 目的  在不同光照条件下,地卓西平马来酸盐(dizocilpine,MK-801)急性处理对斑马鱼幼鱼自发运动和焦虑行为的影响。方法  野生型AB品系斑马鱼幼鱼(5天和7天)暴露在不同浓度MK-801 (0、10、20、50、100、200 μmol/L)溶液中。在光照与黑暗交替条件下,记录斑马鱼幼鱼每分钟游动距离和趋触性。结果  光照条件下,MK 801急性处理能显著降低幼鱼自发运动(P<0.05);黑暗条件下,MK-801急性处理也能降低幼鱼自发运动(P<0.05),但10 μmol/L MK-801对5天幼鱼自发运动无显著影响(P>0.05);黑暗条件下,7天幼鱼在100 μmol/L MK-801作用下抗焦虑能力显著增加,5天幼鱼在20、50 μmol/L MK-801作用下有显著的抗焦虑能力(P<0.05);光照条件下,斑马鱼幼鱼的抗焦虑行为都无显著变化(P>0.05)。结论  MK-801诱导幼鱼自发运动降低;在黑暗条件下,MK-801用药组(20、50、100和200 μmol/L)的幼鱼表现出抗焦虑行为;年龄、药物剂量和光照条件共同作用影响斑马鱼幼鱼的行为模式。     

Serum 25-hydroxyvitamin D at pregnancy and risk of breast cancer in a prospective study

BackgroundSeveral laboratory and epidemiological studies have inversely linked endogenous vitamin D and the risk of breast cancer. The acquisition of vitamin D over time on the relative risk (RR) of the disease development is not known. In a longitudinal study, we evaluated the association between vitamin D levels at pregnancy over time with the risk of breast cancer, and pregnancy-associated breast cancer.MethodThe risk for subsequent development of breast cancer associated with serum 25-hydroxyvitamin (25-OHD) levels was assessed for consecutive (1st and 2nd pregnancy) samples of 100 cases, with mean lag times (μ_t) of 7.4 and 4.6 years between sampling and the diagnosis, and matched (parity, age, year, season) controls. Pregnancy-associated breast cancer (PABC, 111 case–control pairs, μ_t = 1year) risk was also studied. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the lowest quintile as the reference.ResultsSerum 25-OHD level was not associated with an increased risk neither at the 1st nor at the 2nd pregnancy samples (OR = 1.4, 95%CI 0.6–3.4; OR 1.4, 95%CI 0.7–2.8, respectively), but was associated with an increased risk of PABC (OR = 2.7, 95%CI 1.04–6.7).ConclusionGenerally, vitamin D may not be related to breast cancer risk but the increased PABC risk fits the association of vitamin D with the most aggressive cancers, and warrants caution with vitamin D supplementation during pregnancy.     

Inhibitory effect of total lignan from Fructus Arctii on aldose reductase

The potent inhibitory effect of the total lignan from the plant Fructus Arctii on aldose reductase was observed, suggesting its preventive potential on diabetic complications upon long term administration. Copyright © 2009 John Wiley & Sons, Ltd.