Identification of biomarkers for essential hypertension based on metabolomics

AimEssential hypertension (EH) is one of the most important public health problems worldwide. However, the pathogenesis of EH is unclear and early diagnostic methods are lacking. Metabolomics demonstrates great potential for biomarker discovery and the mechanistic exploration of metabolic diseases.Data synthesisThis review included human and animal metabolomics studies related to EH in the PubMed and Web of Science databases between February 1996 and May 2020. The study designs, EH standards, and reported metabolic biomarkers were systematically examined and compared. The pathway analysis was conducted through the online software MetaboAnalyst 4.0.Twenty-two human studies and fifteen animal studies were included in this systematic review. There were many frequently reported biomarkers with consistent trends (e.g., pyruvate, lactic acid, valine, and tryptophan) in human and animal studies, and thus had potential as biomarkers of EH. In addition, several shared metabolic pathways, including alanine, aspartate, and glutamate metabolism, aminoacyl-tRNA biosynthesis, and arginine biosynthesis, were identified in human and animal metabolomics studies. These biomarkers and pathways, closely related to insulin resistance, the inflammatory state, and impaired nitric oxide production, were demonstrated to contribute to EH development.ConclusionsThis study summarized valuable metabolic biomarkers and pathways that could offer opportunities for the early diagnosis or prediction of EH and the discovery of the metabolic mechanisms of EH.     

Plasma matrix metalloproteinase 7, CC-chemokine ligand 18, and periostin as markers for pulmonary sarcoidosis

BackgroundSome patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis.MethodsPlasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics.ResultsPlasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function.ConclusionAmong these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.     

Circulating CCL20: A potential biomarker for active vitiligo together with the number of Th1/17 cells

Background

Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.

PPARγ在子宫内膜异位症中的作用研究进展

现有的研究已阐明激活PPARγ具有抑制炎症反应、抗血管生成等作用,而炎症反应和血管生成均参与了子宫内膜异位症的发生发展,并且PPARγ在正常子宫内膜组织及异位子宫内膜组织均有表达。PPARγ在子宫内膜异位症中的作用受到越来越多的关注,该文就PPARγ在子宫内膜异位症中的意义作一综述。     

Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson’s disease

Introduction: Current treatment of Parkinson’s disease (PD) is limited to symptomatic dopaminergic therapy, while no interventions have been shown to slow down disease progression.

Areas covered: The following article highlights a group of PPAR-γ agonists called thiazolidinediones (TZDs), which are currently being tested for a putative disease-modifying benefit in PD, using pioglitazone as a prototypic compound. PPAR-γ is highly expressed in neurons of the substantia nigra and CNS immune cells. Preclinical data in rodent and primate support an effect of TZDs in preventing and/or arresting neurodegeneration and development of motor symptoms. Although no data on the neuroprotective effect of TZDs is currently available, a clinical trial is ongoing where the primary objective is to assess pioglitazone’s impact on the progression of PD. The trial is also evaluating the drug’s safety concerns.

Expert opinion: The efficacy data from clinical trials must be carefully weighed against the safety concerns. However, given the solid preclinical data, and since the safety data are not yet fully conclusive and limited to the diabetic population, PPAR-γ research in PD can continue with caution. Ideally, drug discovery and development efforts will lead to the identification of new compounds with reduced risk of peripheral side effects.     

Latent autoimmune hepatitis triggered during interferon therapy in patients with chronic hepatitis C

Interferon can induce autoantibodies and autoimmune reactions. This study reviewed the clinical, serological, and HLA phenotypical features of patients who developed autoimmune hepatitis during interferon therapy for chronic hepatitis C, analyzing their response to immunosuppressive treatment. The diagnosis of chronic hepatitis C was based on positivity for viral RNA and a liver biopsy specimen obtained before interferon treatment. Sera were tested for autoantibodies by indirect immunofluorescence assay. HLA typing was performed by applying a standard microlymphocytotoxicity method. Of 144 patients with chronic hepatitis C treated with interferon, 7 women deteriorated during treatment; serum transaminase, γ-globulin, and immunoglobulin G levels increased; and serum autoantibodies became positive. Interferon was interrupted, a diagnosis of autoimmune hepatitis was established, and immunosuppressive therapy was initiated. All patients responded to this treatment. The 7 patients had similar HLA typing to those with autoimmune hepatitis, with DR4 in 2 patients (67%) with type 2 autoimmune hepatitis, and with DR3 and DR52 in 2 (50%) and 4 (100%) patients, respectively, with type 1 autoimmune hepatitis; additionally, 5 patients (71%) had DQ2, and 4 (57%) had both DR52 and DQ2. In female patients with chronic hepatitis C, a genetic susceptibility to autoimmune hepatitis may exist, possibly triggered by immunostimulating effects during interferon therapy. Immunosuppressive treatment has been well tolerated and seems to be effective.     

泪腺炎患者血清性激素变化及其与γ-IFN、IL-4的相关性

目的 观察泪腺炎患者血清中雌二醇(estradiol,E2)、睾酮(testosterone,T)、泌乳素(prolactin,PRL)水平的变化,并探讨这种变化与血清中γ-干扰素(γ-interferon,γ-IFN)、白细胞介素4(interleukin-4,IL-4)变化的关系.方法 收集42例2013年11月至2014年10月我院确诊为泪腺炎的患者炎症期(炎症期组)与炎症缓解期(缓解期组)的血清,40例同年龄段于我院体检的正常人血清作为正常对照组,采用电化学发光法检测血清中E2、T、PRL的水平,酶联免疫吸附法测定血清中γ-IFN、IL-4水平.结果 泪腺炎患者炎症期组血清E2、PRL水平分别为(64.12±35.92) ng·L-1和(17.63±8.59) μg·L-1,显著高于缓解期组的(43.16 ±26.57)ng·L-1和(10.30±5.59) μg·L-1及正常对照组的(41.92±21.68)ng·L-1和(9.08±2.61) μg·L-1,差异均有统计学意义(均为P＜0.05);炎症期组与缓解期组血清T分别为(0.80±1.36) μg·L-1和(0.79±1.42) μg·L-1,与正常对照组的(1.76±2.49) μg·L-1相比差异均有统计学意义(均为P ＜0.05).炎症期组血清γ-IFN、IL-4水平分别为(353.12±108.36)ng·L-1和(1200.43±314.69)ng·L-1,显著高于缓解期组的(192.68±43.16)ng·L-1和(919.38±227.16)ng·L-1及正常对照组的(190.93±36.40)ng·L-1和(853.37±172.31)ng·L-1,差异均有统计学意义(均为P＜0.05).E2与γ-IFN、IL-4水平呈正相关(均为P＜0.05);T与γ-IFN、IL-4水平呈负相关(均为P＜0.05);PRL与γ-IFN、IL-4水平呈正相关(均为P＜0.05).女性患者炎症期组血清γ-IFN水平为(344.46±112.06)ng·L-1,高于男性的(292.98±71.27)ng·L-1(P＜0.05),E2/T比值为665.36,明显高于男性的13.91(P ＜0.05).结论 泪腺炎患者血清中性激素E2、PRL的升高、T的降低及E2/T比例失调可能介导Th1、Th2细胞免疫通路的平衡紊乱从而致病.女性体内高水平的雌激素可能是导致女性易患自身免疫性疾病的主要原因.     

大剂量丙种球蛋白联合纳洛酮治疗乙型脑炎疗效分析

目的：观察大剂量丙种球蛋白联合纳洛酮治疗乙型脑炎的疗效。方法安康市中心医院2012年6月至2014年9月收治的95例乙型脑炎患儿随机分成两组。对照组47例,给予常规综合治疗(抗病毒治疗+营养支持+对症治疗);研究组48例,在常规综合治疗的基础上,给予丙种球蛋白静脉输注1g·kg-1·d-1联合纳洛酮(0.01~0.02)mg/kg治疗。结果研究组患儿平均退热时间、抽搐时间及意识障碍持续时间较对照组明显缩短(t值分别为4.526、3.371、4.487,均P<0.01);研究组较对照组呼吸衰竭发生率明显降低(χ2=14.341,P<0.05);研究组治愈率显著高于对照组(χ2=19.234,P<0.01)。结论丙种球蛋白联合纳洛酮治疗乙型脑炎较单纯综合治疗更为有效,能够显著降低死亡率,提高治愈率,减少后遗症的发生,应在临床治疗中普遍推广及应用。