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.     

五加减正气散化裁对溃疡性结肠炎大鼠干扰素-γ的影响

目的:讨论五加减正气散化裁对溃疡结肠炎(UC)大鼠血中的干扰素-γ(INF-γ)的影响。方法:实验动物分成4组,分别为空白组、模型组、西药组和中药组,采用乙酸诱导法造模,观察大鼠结肠黏膜病理变化,用ELISA法检测大鼠血中INF-γ的水平。结果:空白组大鼠血中INF-γ和结肠黏膜无变化,模型组的大鼠血中INF-γ和结肠黏膜变化明显,西药组与中药组大鼠血中INF-γ和结肠黏膜无明显变化。西药组、中药组与空白组间差异无统计学意义;模型组与空白组比较,大鼠血清中INF-γ显著升高,结肠黏膜充血、水肿、糜烂并有溃疡形成,两者之间差异有统计学意义(P<0.05);模型组与西药组、中药组间大鼠血清中INF-γ显著升高,结肠黏膜充血、水肿、糜烂并有溃疡形成,差异有统计学意义(P<0.05)。结论:五加减正气散化裁能干预实验性UC大鼠血中的INF-γ的活性,对UC大鼠结肠溃疡面有修复和保护作用。     

4种宫内节育器使用36个月效果观察

目的:比较4种宫内节育器(IUD)的使用效果.方法:对分别放置4种IUD的3 000例育龄妇女随访36个月,对比观察其的使用效果、副反应等.结果:放置吉妮致美IUD 1 200例、爱母功能性IUD 1 000例、母体乐铜375IUD 400例、活性γ型IUD 400例,4种IUD 3年带器妊娠率分别为1.54/百妇女年、4.49/百妇女年、1.92/百妇女年、3.53/百妇女年,差异有统计学意义(P＜0.05)；脱落率分别为4.07/百妇女年、5.36/百妇女年、4.80/百妇女年、5.62/百妇女年,差异有统计学意义(P＜0.05)；在疼痛和出血副反应发生率方面,以母体乐铜375 IUD较高.结论:吉妮致美IUD避孕效果较好,副作用少,值得临床应用.     

γ-Rays-generated ROS induce apoptosis via mitochondrial and cell cycle alteration in smooth muscle cells

Abstract

Purpose: γ-rays (IR) cause an increase in intracellular calcium [Ca²⁺], alters contractility and triggers apoptosis via the activation of protein kinase C in intestinal guinea pig smooth muscle cells. The present study investigated the role of the mitochondria in these processes and characterized proteins involved in IR-induced apoptosis.

Materials and methods: Intestinal smooth muscle cells were exposed to 10–50 Gy from a ⁶⁰Co γ-source. Reactive oxygen species (ROS) levels were measured by colourimetry with a fluorescente probe. Protein expression was analyzed by immunoblotting and immunofluorescence.

Results: Apoptosis was inhibited by glutathione, possible by inhibiting the generation or scavenging ROS. Apoptosis was mediated by the mitochondria releasing cytochrome c leading to caspase 3 activation. IR increased the expression of the cyclins A, B2 and E and led to unbalanced cellular growth in an absorption dose-dependent manner. However, radiation did not induce alterations in the mitochondrial ultrastructure or in transmembrane electric potential. In contrast, IR increased the nuclear expression of cytoplasmic proteins and cyclins A and E.

Conclusion: Smooth muscle cells subjected to IR undergo mitochondrial-mediated apoptosis that involves oncoproteins activation and preserves mitochondrial structure. IR also cause alterations in the expression and localization of both pro- and anti-apoptotic proteins.     

Brief overview of selected approaches in targeting pancreatic adenocarcinoma

Introduction: Pancreatic adenocarcinoma (PDAC) has the worst prognosis of any major malignancy, with 5-year survival painfully inadequate at under 5%. Investigators have struggled to target and exploit PDAC unique biology, failing to bring meaningful results from bench to bedside. Nonetheless, in recent years, several promising targets have emerged.

Areas covered: This review will discuss novel drug approaches in development for use in PDAC. The authors examine the continued efforts to target Kirsten rat sarcoma viral oncogene homolog (KRas), which have recently been successfully abated using novel small interfering RNA (siRNA) eluting devices. The authors also discuss other targets relevant to PDAC including those downstream of mutated KRas, such as MAPK kinase and phosphatidylinositol 3-kinase.

Expert opinion: Although studies into novel biomarkers and advanced imaging have highlighted the potential new avenues toward discovering localized tumors earlier, the current therapeutic options highlight the fact that PDAC is a highly metastatic and chemoresistant cancer that often must be fought with virulent, systemic therapies. Several newer approaches, including siRNA targeting of mutated KRas and enzymatic depletion of hyaluronan with PEGylated hyaluronidase are particularly exciting given their early stage results. Further research should help in elucidating their potential impact as therapeutic options.     

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.

γ-谷氨酰转肽酶对急性肺栓塞早期病死率的预测价值

目的探讨γ-谷氨酰转肽酶（γ-glutamyl transferase，GGT）与急性肺动脉栓塞（acute pulmonary embolism，APE）患者早期病死率之间的关系。方法共入组了109例确诊为APE的患者。使用受试者工作曲线（ROC）得出GGT的最佳预测早期病死率临界值为〉52IU／L，敏感性91．7％和特异性61．9％。APE患者在GGT临界值的基础上分为没有增加（I组）或增加（II组），对两组基线特征、血流动力学、超声心动图及实验室检查结果进行比较。结果109例患者中，13例（11．9％）在住院期间死亡。在这13例患者中，有2例（3．2％）进入I组，11例（23．9％）进入II组，差异有统计学意义（P=0．001）。GGT与人院时心率（r=0．502，P〈0．001）、收缩压（r=0．505，P〈0．001）、舒张压（r=-0．296，P=0．002）、动脉血氧分压r=-0．477，P〈0．001）、三尖瓣关闭不全的严重程度（r=0．348，P=0．001）、肌钙蛋白I（r=0．369．P=0．035）相关。结论GGT升高的急性APE患者早期死亡风险明显升高。GGT升高与较差的血流动力学指标相关。GGT可能有助于APE患者的危险分层。     

Scintillation proximity assay in lead discovery

Background: Scintillation proximity assay (SPA) is a homogeneous scintillant bead-based platform for the measurement of biological processes and plays an important role in the identification of active chemical entities in drug discovery. Objective: The design and development of solid-phase SPA approaches are examined and compared with alternative non-radiometric fluorescence-based technologies. Methods: This review provides background on the principle of SPA and its application to biomolecular interactions from a variety of biological sources. Conclusion: The SPA approach is well suited to the demands of commercial high volume automation and assay miniaturization for target-based high-throughput screening campaigns on synthetic and natural product libraries as well as for benchtop characterization and confirmation studies. In the near future, innovations in the way SPA and fluorescence-based screening strategies are multiplexed will improve our comprehensive understanding of cellular system biology and dramatically advance the lead discovery process for the treatment of complex target-related disorders.