摘要:
Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and neuropathologic entity characterized by early onset parkinsonism and localized neuronal degeneration in the substantia nigra without Lewy bodies. The purpose of this study is to identify the genetic defect in a Chinese pedigree with familial AR-JP and to explore genotype-phenotype correlation. A three-generation Chinese Han pedigree with familial AR-JP was recruited in this study, and the patients in the pedigree presented with typical but heterogeneous clinical features of AR-JP and with different ages of disease onset. Exome sequencing and Sanger sequencing were conducted in the index case diagnosed as juvenile parkinsonism and a homozygous variant, c.850G > C (p.G284R), in the parkin gene was identified. The homozygous variant co-segregated with the disease in the family and was absent in 800 controls. The homozygous variant, c.850G > C (p.G284R), in the parkin gene is possibly responsible for AR-JP in this pedigree. Heterozygous c.850G > C mutation carriers were free of any neurological symptoms, consistent with a loss-of-function mechanism of the parkin mutations. These findings may provide new insights into the cause and diagnosis of AR-JP and have implications for genetic counseling. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
期刊:
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE,2016年12:85-94 ISSN:1178-2005
通讯作者:
Xu, Haiyu;Yang, Hongjun
作者机构:
[Dong, Ling; Yu, Guohua] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China.;[Yu, Guohua; Zhang, Yanqiong; Li, Defeng; Li, Junfang; Zhang, Yi; Xu, Haiyu; Xu, HY; Yang, Hongjun; Geng, Ya] China Acad Chinese Med Sci, Inst Chinese Mat Med, 16 Nanxiaojie, Beijing 100700, Peoples R China.;[Ren, Weiqiong] Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Changsha, Hunan, Peoples R China.;[Li, Junfang] Tianjin Univ Tradit Chinese Med, Sch Chinese Mat Medica, Tianjin, Peoples R China.;[Geng, Ya] Shandong Univ Chinese Med, Sch Basic Med, Jinan, Peoples R China.
通讯机构:
[Xu, HY; Yang, HJ] C;China Acad Chinese Med Sci, Inst Chinese Mat Med, 16 Nanxiaojie, Beijing 100700, Peoples R China.
关键词:
traditional Chinese medicine;Yin–Huang–Qing–Fei capsule;chronic bronchitis;network pharmacology;asthma pathway
摘要:
For decades in China, the Yin–Huang–Qing–Fei capsule (YHQFC) has been widely used in the treatment of chronic bronchitis, with good curative effects. Owing to the complexity of traditional Chinese herbal formulas, the pharmacological mechanism of YHQFC remains unclear. To address this problem, a network pharmacology-based strategy was proposed in this study. At first, the putative target profile of YHQFC was predicted using MedChem Studio, based on structural and functional similarities of all available YHQFC components to the known drugs obtained from the DrugBank database. Then, an interaction network was constructed using links between putative YHQFC targets and known therapeutic targets of chronic bronchitis. Following the calculation of four topological features (degree, betweenness, closeness, and coreness) of each node in the network, 475 major putative targets of YHQFC and their topological importance were identified. In addition, a pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes pathway database indicated that the major putative targets of YHQFC are significantly associated with various pathways involved in anti-inflammation processes, immune responses, and pathological changes caused by asthma. More interestingly, eight major putative targets of YHQFC (interleukin [IL]-3, IL-4, IL-5, IL-10, IL-13, FCER1G, CCL11, and EPX) were demonstrated to be associated with the inflammatory process that occurs during the progression of asthma. Finally, a molecular docking simulation was performed and the results exhibited that 17 pairs of chemical components and candidate YHQFC targets involved in asthma pathway had strong binding efficiencies. In conclusion, this network pharmacology-based investigation revealed that YHQFC may attenuate the inflammatory reaction of chronic bronchitis by regulating its candidate targets, which may be implicated in the major pathological processes of the asthma pathway.
摘要:
Glaucoma, the second leading cause of blindness, is an irreversible optic neuropathy. The mechanism of optic nerve injury caused by glaucoma is undefined at present. There is no effective treatment method for the injury. Stem cells have the capacity of self-renewal and differentiation. These two features have made them become the research focus on improving the injury at present. This paper reviews the application progress on different types of stem cells therapy for optic nerve injury caused by glaucoma.
作者机构:
[Xu, G. C.; Jiao, L. Y.] Gannan Med Univ, Ganzhou 341000, Peoples R China.;[Li, Y. C.; Wang, J. X.] Hunan Univ Tradit Chinese Med, Postgrad Sch, Changsha 410208, Hunan, Peoples R China.;[Li, Y. C.] Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Neurol, Changsha 410007, Hunan, Peoples R China.
会议名称:
5th Chinese Congress on Gerontology and Health Industry (CCGI)
通讯机构:
[Qin, Li] H;Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词:
Long noncoding RNAs;Nuclear receptor;SRA;Transcriptional coactivator
摘要:
Steroid receptor RNA activator (SRA) is a type of long noncoding RNA (lncRNA) which coordinates the functions of various transcription factors, enhances steroid receptor-dependent gene expression, and also serves as a distinct scaffold. The novel, profound and expanded roles of SRA are emerging in critical aspects of coactivation of nuclear receptors (NRs). As a nuclear receptor coactivator, SRA can coactivate androgen receptor (AR), estrogen receptor α (ERα), ERβ, progesterone receptor (PR), glucocorticoid receptor (GR), thyroid hormone receptor and retinoic acid receptor (RAR). Although SRA is one of the least well-understood molecules, increasing studies have revealed that SRA plays a key role in both biological processes, such as myogenesis and steroidogenesis, and pathological changes, including obesity, cardiomyopathy, and tumorigenesis. Furthermore, the SRA-related signaling pathways, such as the mitogen-activated protein kinase (p38 MAPK), Notch and tumor necrosis factor α (TNFα) pathways, play critical roles in the pathogenesis of estrogen-dependent breast cancers. In addition, the most recent data demonstrates that SRA expression may serve as a new prognostic marker in patients with ER-positive breast cancer. Thus, elucidating the molecular mechanisms underlying SRA-mediated functions is important to develop proper novel strategies to target SRA in the diagnosis and treatment of human diseases.
摘要:
Aim To study the relationship between erectile dysfunction and type 2 diabetes mellitus (T2DM)/metabolic syndrome (MetS). Methods This prospective study invited male patients with T2DM attending for a routine outpatient check-up to complete two questionnaires. A general questionnaire was used to collect demographic and clinical characteristics, while sexual function was assessed using the International Index of Erectile Function scoring system. The prevalence of MetS in this patient population was determined using information from the general questionnaire. Risk factors for erectile dysfunction were identified using univariate and multivariate logistic regression analyses. Results A total of 175 patients provided valid questionnaires; of these, 148 (84.6%) had MetS. The prevalence of erectile dysfunction was 90.9% (159/175) in the entire survey population compared with 89.2% (132/148) in patients with MetS. Multivariate logistic regression analysis identified the following risk factors for erectile dysfunction in patients with T2DM and/or MetS: age, blood pressure and duration of diabetes. Conclusion These current findings suggest that the MetS and its components have a negative impact on male erectile function.
期刊:
International Journal of Molecular Sciences,2016年17(3):429 ISSN:1422-0067
通讯作者:
Liao, Duan-Fang
作者机构:
[Du, Ke; Liu, Chan; Chen, Jian-Xiong; Zheng, Xi-Long; Shi, Ya-Ning; Ao, Bao-Xue; Liao, Duan-Fang; Qin, Li] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.;[Zhu, Neng] Hunan Univ Chinese Med, Hosp 1, Dept Urol, Changsha 410208, Hunan, Peoples R China.;[Chen, Jian-Xiong] Univ Mississippi, Med Ctr, Sch Med, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA.;[Zheng, Xi-Long] Univ Calgary, Libin Cardiovasc Inst Alberta, Dept Biochem & Mol Biol, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
通讯机构:
[Liao, Duan-Fang] H;Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China.
关键词:
atherosclerosis;caveolae;caveolin-1;inflammation;reverse cholesterol transport
摘要:
Lipid disorder and inflammation play critical roles in the development of atherosclerosis. Reverse cholesterol transport is a key event in lipid metabolism. Caveolae and caveolin-1 are in the center stage of cholesterol transportation and inflammation in macrophages. Here, we propose that reverse cholesterol transport and inflammation in atherosclerosis can be integrated by caveolae and caveolin-1.
摘要:
Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, effectively reduces plasma cholesterol, but its effect on atherosclerosis is unclear. Foam cell formation has been implicated as a key mediator during the development of atherosclerosis. The purpose of this study was to investigate the effects of ezetimibe on foam cell formation and explore the underlying mechanism. Our results showed that ezetimibe reduced atherosclerotic lesions in apolipoprotein E deficient (apoE-/-) mice by lowering cholesterol levels. Treatment of macrophages with Chol:MβCD resulted in foam cell formation, which was concentration-dependently inhibited by the presence of ezetimibe. Mechanically, ezetimibe treatment downregulated the expression of CD36 and scavenger receptor class B1 (SR-B1), but upregulated the expression of apoE and caveolin-1 in macrophage-derived foam cells, which kept consistent with our microarray results. Moreover, treatment with ezetimibe abrogated the increase of phospho-extracellular signal regulated kinase (ERK) 1/2 and their nuclear accumulation in foam cells. Inhibition of the MAPK pathway by the MEK inhibitor PD98059 attenuated the inhibitory effect of ezetimibe on the expression of p-ERK1/2 and caveolin-1. Taken together, our results showed that ezetimibe suppressed foam cell formation via the caveolin-1/MAPK signaling pathway, suggesting that inhibition of foam cell formation might be a novel mechanism underlying the anti-atherosclerotic effect of ezetimibe. This article is protected by copyright. All rights reserved.
摘要:
Objective: The aim of the present study was to investigate the effects of Longdanxiegan formula granule (LDXGFG), a Chinese traditional medicine on Toll-like receptor (TLR) pathway in recurrent genital herpes. Materials and Methods: An experimental recurrent genital herpes model was constructed using herpes guinea pig model. The effect of LDXGFG on expression levels of TLR pathway genes were detected using real-time polymerase chain reaction. Furthermore, the dendritic cells and Langerhans cells were isolated and the TLR pathway genes of these cells were assayed after LDXGFG treatment. Results: The result suggested two different expression patterns of TLR pathway genes in genital herpes and recurrent genital herpes, including upregulated genes and downregulated genes. TLR1, TLR4, TLR6, TLR7, TLR8, TLR9, and TLR10 showed a significant decrease while, TLR2, TLR3, and TLR5 increased in genital herpes and recurrent genital herpes guinea pigs. Meanwhile, the downregulated genes in genital herpes and recurrent genital herpes were stimulated by LDXGFG. By contrast, the upregulated genes decreased significantly after LDXGFG treatment. In both dendritic cells and Langerhans cells, the TLR pathway genes exhibited same pattern: the LDXGFG corrected the abnormal expression of TLR pathway genes. Conclusion: The present results suggest that LDXGFG is an alternative, inexpensive, and lasting-effect medicine for herpes simplex virus 2 infection. Copyright (C) 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC.
作者机构:
[Huang, Z. Q.] Gannan Med Univ, Coll Pharm, Ganzhou 341000, Peoples R China.;[Li, Y. C.; Wang, J. X.] Hunan Univ Tradit Chinese Med, Postgrad Sch, Changsha 410208, Hunan, Peoples R China.;[Li, Y. C.] Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Neurol, Changsha 410007, Hunan, Peoples R China.
会议名称:
5th Chinese Congress on Gerontology and Health Industry (CCGI)
关键词:
BIOMECHANICS;intraocular;glaucoma;sclera;intraocular pressure;finite element models
摘要:
Accumulating evidence indicates that glaucoma is a multifactorial neurodegenerative disease characterized by the loss of retinal ganglion cells (RGC), resulting in gradual and progressive permanent loss of vision. Reducing intraocular pressure (IOP) remains the only proven method for preventing and delaying the progression of glaucomatous visual impairment. However, the specific role of IOP in optic nerve injury remains controversial, and little is known about the biomechanical mechanism by which elevated IOP leads to the loss of RGC. Published studies suggest that the biomechanical properties of the sclera and scleral lamina cribrosa determine the biomechanical changes of optic nerve head, and play an important role in the pathologic process of loss of RGC and optic nerve damage. This review focuses on the current understanding of biomechanics of sclera in glaucoma and provides an overview of the possible interactions between the sclera and IOP. Treatments and interventions aimed at the sclera are also discussed.
作者机构:
[Li, Yingchen; Cheng, Qilai] Hunan Univ Tradit Chinese Med, Postgrad Sch, Changsha 410208, Hunan, Peoples R China.;[Hu, Guoheng] Hunan Univ Tradit Chinese Med, Dept Neurol, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.
通讯机构:
[Hu, Guoheng] H;Hunan Univ Tradit Chinese Med, Dept Neurol, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.
关键词:
human umbilical cord;mesenchymal stem cells;ischemic stroke;cellular therapy;transplantation
摘要:
Ischemic stroke is a focal cerebral insult that often leads to many adverse neurological complications severely affecting the quality of life. The prevalence of stroke is increasing throughout the world, while the efficacy of current pharmacological therapies remains unclear. As a neuroregenerative therapy, the implantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) has shown great possibility to restore function after stroke. This review article provides an update role of hUC-MSCs implantation in the treatment of ischemic stroke. With the unique “immunosuppressive and immunoprivilege” property, hUC-MSCs are advised to be an important candidate for allogeneic cell treatment. Nevertheless, most of the treatments are still at primary stage and not clinically feasible at the current time. Several uncertain problems, such as culture conditions, allograft rejection, and potential tumorigenicity, are the choke points in this cellular therapy. More preclinical researches and clinical studies are needed before hUC-MSCs implantation can be used as a routinely applied clinical therapy.
期刊:
Evidence-Based Complementary and Alternative Medicine,2015年2015:328642 ISSN:1741-427X
通讯作者:
Li, Linghui
作者机构:
[Yang, Shaofeng; Li, Linghui; Zhu, Liguo] China Acad Chinese Med Sci, Wangjing Hosp, Dept Spine, Huajiadi St, Beijing 100102, Peoples R China.;[Yang, Shaofeng] Hunan Univ Chinese Med, Hosp 1, Dept Spine, Changsha 410007, Hunan, Peoples R China.;[Wang, Shangquan] China Acad Chinese Med Sci, Wangjing Hosp, Dept Gen Orthoped, Beijing 100102, Peoples R China.;[Gong, Hao] Changping Hosp Integrated Chinese & Western Med, Dept Orthopaed, Beijing 102208, Peoples R China.;[Wei, Xu] China Acad Chinese Med Sci, Wangjing Hosp, Dept Sci Res, Beijing 100102, Peoples R China.
通讯机构:
[Li, Linghui] C;China Acad Chinese Med Sci, Wangjing Hosp, Dept Spine, Huajiadi St, Beijing 100102, Peoples R China.