共轭亚油酸对肥胖大鼠PPARγ基因表达及血清瘦素水平的影响

目的　研究不同剂量共轭亚油酸 (CLA)对饮食诱导肥胖大鼠PPARγ基因、瘦素、血糖、血脂的影响。方法　选用雄性Wistar大鼠 ,随机分为对照组、高脂组、高脂 +CLA组 (每 10 0g饲料含CLA分别为 0 75g、1 5 0g、3 0 0g) ,于第 12周末处死动物 ,计算脂 体比 ,测定大鼠血糖、血脂及瘦素水平 ,并应用RT PCR的方法检测大鼠白色脂肪组织过氧化物酶体增殖物激活受体γ(PPARγ)的表达水平。结果　CLA可降低肥胖大鼠血糖、甘油三酯 (TG)、总胆固醇 (TC)及瘦素水平 ,增加脂肪组织PPARγmRNA的表达水平。结论　CLA可降低肥胖大鼠血糖、血脂 ,并可通过激活PPARγ下调瘦素水平 ,有改善肥胖大鼠的瘦素抵抗作用。     

急性期川崎病与过敏性紫癜患儿血浆趋化因子的比较

目的:探讨川崎病(KD)与过敏性紫癜(HSP)发病机制中炎性细胞的参与是否存在差异。方法:通过采用酶联免疫吸附试验(ELISA)检测确诊的15例急性期KD患儿、12例HSP患儿及10名健康对照组儿童的血浆干扰素诱导蛋白10(IP-10)和单核细胞趋化蛋白1(MCP-1)水平,判断KD与HSP发病机制中单核细胞参与的情况。结果:KD组IP-10(394.2±176.4)pg/m l和MCP-1(420.5±163.4)pg/m l水平较HSP组IP-10(94.8±66.4)pg/m l和MCP-1(109.2±76.6)pg/m l水平均明显升高,差异性显著(P<0.05);但HSP组与对照组IP-10(76.4±46.5)pg/m l和MCP-1(87.7±47.8)pg/m l水平比较,差异不明显(P>0.05)。结论:单核细胞在KD发病机制中可能发挥着重要的作用;与其相比,在HSP发病机制中可能不涉及单核细胞参与。     

An update on the efficacy of non-steroidal anti-inflammatory drugs in Alzheimer's disease

Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD), especially for patients carrying one or more ?4 allele of the apolipoprotein E. The biological mechanism of this protection is not completely understood and may involve inhibition of COX activity, inhibition of β-amyloid_1-42 (Aβ42) production and aggregation, inhibition of β-secretase activity, activation of PPAR-γ or stimulation of neurotrophin synthesis. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and COX-2 selective NSAIDs in AD patients produced negative results. A secondary prevention study with rofecoxib in patients with mild cognitive impairment and a primary prevention study with naproxen and celecoxib in elderly subjects with a family history of AD were also negative. All these failures have diminished the hope that NSAIDs could be beneficial in the treatment of AD. It is hypothesized that the chronic use of NSAIDs may be beneficial only in the normal brain by inhibiting the production of Aβ42. Once the Aβ deposition process has started, NSAIDs are no longer effective and may even be detrimental because of their inhibiting activity on activated microglia of the AD brain, which mediates Aβ clearance and activates compensatory hippocampal neurogenesis.     

Therapeutic potential of Notch inhibition in T-cell acute lymphoblastic leukemia: rationale,caveats and promises

T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy that presents with poor prognosis. Treatment relies on the application of aggressive therapies that produce deleterious side-effects, justifying the quest for novel, more efficient and selective molecular targeting agents. Mutations leading to abnormal Notch-1 activity are present in more than half of the T-ALL patients, underscoring the potential therapeutic relevance of targeting Notch-1 inhibition and further reinforcing the need to better comprehend the mechanisms by which Notch-1 drives T cell leukemogenesis. Clinical application of γ-secretase inhibitors to block Notch signaling in T-ALL revealed new challenges that involve improvement of the therapeutic benefit and reduction of intestinal toxicity. Here, we review the latest advances in the development and use of Notch antagonists and summarize the current knowledge on Notch function in T-ALL to understand how it may translate into novel therapeutic strategies that increment the efficiency of Notch inhibition.     

A Novel GAP460 Biopolymer for Use as a Carrier in Drug-Delivery Applications

We synthesized a new non-toxic biopolymer (GAP460) containing γ,L-glutamic acid and aspartate (Asp). Conjugates of GAP460 and cisplatin exhibited a drug-carrying capacity of nearly 40%, 3-times higher than γ-PGA and dramatically decreasing the amount of biopolymer required for high-dose delivery. Treatment with GAP460-cisplatin conjugate (PACC) not only effectively inhibited tumor growth in nude mice, but also resulted in extended survival and lower nephrotoxicity, suggesting that GAP460 could be used as an effective carrier for drug delivery and that PACC may have potential therapeutic applications in the clinical treatment of cancer.     

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.