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1.
Exercise‐induced physiological hypertrophy provides protection against cardiovascular disease, whereas disease‐induced pathological hypertrophy leads to heart failure. Emerging evidence suggests pleiotropic roles of melatonin in cardiac disease; however, the effects of melatonin on physiological vs pathological cardiac hypertrophy remain unknown. Using swimming‐induced physiological hypertrophy and pressure overload‐induced pathological hypertrophy models, we found that melatonin treatment significantly improved pathological hypertrophic responses accompanied by alleviated oxidative stress in myocardium but did not affect physiological cardiac hypertrophy and oxidative stress levels. As an important mediator of melatonin, the retinoid‐related orphan nuclear receptor‐α (RORα) was significantly decreased in human and murine pathological hypertrophic cardiomyocytes, but not in swimming‐induced physiological hypertrophic murine hearts. In vivo and in vitro loss‐of‐function experiments indicated that RORα deficiency significantly aggravated pathological cardiac hypertrophy, and notably weakened the anti‐hypertrophic effects of melatonin. Mechanistically, RORα mediated the cardioprotection of melatonin in pathological hypertrophy mainly by transactivation of manganese‐dependent superoxide dismutase (MnSOD) via binding to the RORα response element located in the promoter region of the MnSOD gene. Furthermore, MnSOD overexpression reversed the pro‐hypertrophic effects of RORα deficiency, while MnSOD silencing abolished the anti‐hypertrophic effects of RORα overexpression in pathological cardiac hypertrophy. Collectively, our findings provide the first evidence that melatonin exerts an anti‐hypertrophic effect on pathological but not physiological cardiac hypertrophy via alleviating oxidative stress through transactivation of the antioxidant enzyme MnSOD in a RORα‐dependent manner.  相似文献   
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目的:探讨肝脏异维甲酸受体α( RXRα)的基因组靶点特征及其下游通路与脂代谢的关系。方法将6只小鼠随机分为观察组和对照组各3只,分别给予维甲酸150 mg/( kg· d)和等量生理盐水灌胃,共7 d,测定血脂,并用染色体免疫沉淀测序和定量PCR比较RXRα靶基因谱和基因表达差异。结果观察组血清胆固醇和三酰甘油浓度较对照组显著降低(P<0.05),肝脏RXRα的基因组靶点和靶基因数均较对照组增加,以转录起始区靶点增幅最大(<58%)。 RXRα的下游通路包括氧化还原、脂肪酸代谢和脂质转运等。观察组脂代谢相关靶基因中<48%(11/23)显著下调,22%(5/23)上调。结论肝脏RXRα及其下游通路是介导维甲酸调控脂代谢通路的重要因子。  相似文献   
4.
多指标-响应曲面法优选酒炖熟地黄最佳炮制工艺   总被引:3,自引:2,他引:1  
目的基于响应曲面技术,应用HPLC法定量测定,从多指标、综合评价的角度建立酒炖熟地黄的最佳炮制工艺。方法采用HPLC定量分析,以地黄苷D、益母草苷、5-羟甲基糠醛(5-HMF)和毛蕊花糖苷为评价指标,采用响应曲面设计法考察地黄浸润时间、加黄酒量、炖制时间、干燥温度、干燥时间对酒炖熟地黄炮制工艺的影响,寻找出最佳炮制工艺。结果色谱柱为Tnature-C_(18)柱(250 mm×4.6 mm,5μm),体积流量为1 mL/min,柱温为25℃。地黄苷D和益母草苷定量测定:流动相为乙腈-0.1%磷酸水溶液(4∶96),检测波长为203 nm;5-HMF和毛蕊花糖苷定量测定:流动相为乙腈-0.1%磷酸水溶液,梯度洗脱:0~15 min,11%乙腈;15~15.1 min,11%~16%乙腈;15.1~50 min,16%乙腈;检测波长为334 nm。酒炖熟地黄的最佳工艺为100 kg生地加入黄酒60 kg,浸润12 h,密闭炖制38 h,在76℃干燥33 h。结论所建立的HPLC法稳定可行,适合所选成分的测定。采用响应面法建立的模型相对准确,可以较好地预测4种成分含量;优选的酒炖熟地黄炮制工艺方法可行,为制定熟地黄的质量标准和现代研究提供了科学依据。  相似文献   
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Although acne is not an infectious disease, oral antibiotics have remained a mainstay of treatment over the last 40 years. The anti‐inflammatory properties of oral antibiotics, particularly the tetracyclines, are efficacious in treating inflammatory acne lesions. Common prescribing practices in Dermatology exert significant selection pressure on bacteria, contributing to the development of antibiotic resistance. Antibiotic use for acne not only promotes resistance in Propionibacterium acnes, but also affects other host bacteria with pathogenic potential. This review will summarize the commonly used treatments for acne vulgaris, and how they should be combined as rational treatment. The indications for using oral antibiotics in acne will be highlighted. Strategies described in the literature to conserve the utility of oral antibiotics will be summarized. These include limiting the duration of antibiotic therapy, concomitant use of a topical non‐antibiotic agent, use of subantimicrobial dose doxycycline, and the introduction of topical dapsone.  相似文献   
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Isotretinoin (Iso) is the most effective drug against severe nodulocystic acne. As a synthetic oral retinoid, Iso exerts its actions by modulating cell growth and differentiation. Targeting all the pathophysiologic processes in acne development, Iso has been considered to be an unique drug, however it has several side effects. While chelitis, xerosis, ocular sicca, arthralgia, myalgia, headache, hyperlipidemia are the most common side effects, teratogenicity and depressive symptoms are the most concerning ones. In addition, Iso has unusual side effects which have been described for the first time in the literature. Here, we report a remarkable side effect of Iso in a 23-years-old male patient with retinoid dermatitis affecting the external uretral meatus. To our knowledge, only few cases of retinoid dermatitis in the urethral mucosa due to Iso have been reported in the literature so far.  相似文献   
7.
Punctate palmoplantar keratoderma type 1 (PPKP1) is a rare autosomal dominant disorder of keratinization, clinically characterized by punctate keratotic papules affecting the palmoplantar skin. Loss‐of‐function mutations in AAGAB have recently been reported as a cause of PPKP1. Despite the discovery of the genetic cause of PPKP1, pathogenesis‐based therapies are still unavailable. Moreover, little is known about the effectiveness of treatments for PPKP1. In this study, we analyzed a Japanese woman with PPKP1 and identified a novel frame‐shift mutation c.195_198del4 (p.Lys66Phefs*43) in AAGAB. Moreover, low‐dose etretinate was effective in improving the PPKP1 lesions in our patient. Our published work review identified only eight cases of PPKP1 with successful response to topical or systemic treatments. Notably, six of the cases were successfully treated with systemic retinoids. Thus, this study clearly provides further evidence that PPKP1 is caused by AAGAB mutations and that systemic retinoids are the most promising current treatment for PPKP1.  相似文献   
8.
《Medical hypotheses》2014,82(6):1059-1062
Idiopathic intracranial hypertension is a common disorder affecting mainly healthy, young, overweight women. The pathogenesis of this condition is unknown, but it has been shown to follow treatment with several compounds including corticosteroids and vitamin A derivatives. This paper will offer a novel hypothesis and insight on the pathogenesis of drug induced intracranial hypertension following a review and analysis of the literature. Both corticosteroids and vitamin A derivatives have been shown to upregulate the expression of aquaporin 1, a water channel protein. Aquaporin 1 is widely distributed in the human brain and is associated with water secretion into the subarachnoid space. Aquaporin 1 was also shown to participate in the regulation of weight. Agents used for treating idiopathic intracranial hypertension reduce aquaporin 1 expression. Based on these observations, we propose that aquaporin 1 has a pathogenetic role in drug induced idiopathic intracranial hypertension. Over expression of this gene causes increased intracranial pressure, and downregulation reduces pressure and alleviates the symptomatology and complications of idiopathic intracranial hypertension.  相似文献   
9.
Psoriasis is a chronic inflammatory disease of the skin which can occur at any age‐group. Psoriasis in childhood is not uncommon and has genetic susceptibility but usually, an environmental trigger such as infection is thought to initiate the disease process. Pediatric psoriasis has profound effects on both physical and psychosocial health of the patient. Treatment of mild psoriasis can be done with topical therapies but those which do not respond to topical therapies can be treated with phototherapy and systemic therapies. The use of systemic therapies in childhood is mainly based on the published data, case series, expert opinion and the experience as there is the lack of controlled trials in the age group. Based on the experience retinoids are probably the second line drugs for the treatment of pediatric psoriasis which do not respond to topical therapies and phototherapy. Using acitretin in a low dose and with proper physical examinations and laboratory investigations will reduce the hazard of potential serious adverse events. This article gives the review of the use of acitretin in pediatric psoriasis.  相似文献   
10.
全反式维甲酸(all-trans retinoid acid,ATRA)是维生素A的重要中间代谢物,其在调节眼部组织多种细胞的增生、分化以及维持上皮组织的正常角化等过程中均发挥重要作用.ATRA在角结膜瘢痕性病变如Stevens-Johnson综合征以及角膜损伤性疾病中可能具有独特的疗效,同时ATRA在抑制角膜移植术后的免疫排斥反应和治疗局部角膜缘干细胞缺乏症也具有良好的应用前景.  相似文献   
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