炔雌醇环丙孕酮片用于PCOS不孕治疗中的效果

目的 分析炔雌醇环丙孕酮片(达英-35)、二甲双胍联合克罗米芬序贯用于治疗多囊卵巢综合征不孕的临床效果.方法 选取在医院接受治疗的多囊卵巢综合征不孕患者88例,选取时间为2017年10月—2018年12月,随机将所有患者分为2组,即对照组(44例)、观察组(44例),对照组患者行炔雌醇环丙孕酮片、克罗米芬序贯治疗,观察组患者行达英-35、二甲双胍联合克罗米芬序贯治疗.结果 经过治疗后,观察组患者的妊娠率为86.36%,明显高于对照组患者的妊娠率,数据差异显著,P<0.05;治疗后,两组患者的LH、FSH、T、E2等激素水平与治疗前对比,差异显著,P<0.05;治疗后,观察组患者的LH、FSH、T、E2等激素水平与对照组对比,数据差异较明显,P<0.05.结论 多囊卵巢综合征不孕患者接受炔雌醇环丙孕酮片、二甲双胍联合克罗米芬序贯治疗,可以改善患者的激素水平,提高患者的妊娠几率.     

西格列汀联合二甲双胍治疗肥胖型2型糖尿病的疗效及对体脂含量情况分析

目的研究肥胖型2型糖尿病患者联合采用西格列汀、二甲双胍治疗的临床效果。方法选择2018年10月—2020年4月该院100例肥胖型2型糖尿病患者为研究对象,采用随机数表法分成常规组和治疗组,每组50例。常规组予二甲双胍治疗,治疗组予二甲双胍+西格列汀治疗。比较两组治疗效果、血糖指标、体脂含量、胰岛功能指标及不良反应。。结果两组治疗效果比较,差异有统计学意义(P<0.05)。治疗后常规组血糖指标高于治疗组,差异有统计学意义(t=8.183、4.828、18.158,P<0.05)。治疗后常规组体脂含量高于治疗组,差异有统计学意义(t=5.993、7.657、4.420,P<0.05)。治疗后两组胰岛功能比较,差异有统计学意义(t=5.898、5.283、16.033,P<0.05)。常规组不良反应总发生率低于治疗组,但差异无统计学意义(χ²=0.136,P=0.712)。结论西格列汀、二甲双胍联合治疗肥胖型2型糖尿病效果确切。     

Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Endogenous testosterone determines metformin action on prolactin levels in hyperprolactinaemic men: A pilot study

Metformin was found to reduce elevated prolactin levels in women but not in men. The current study was aimed at investigating whether endogenous testosterone determines the impact of metformin on lactotroph function in men. This prospective case‐control study included 28 men with recently diagnosed type 2 diabetes mellitus and mild or moderate hyperprolactinaemia, 14 of whom had low testosterone levels, while in the remaining 14 ones' testosterone levels were within the reference range. All participants received metformin (2.55‐3 g daily) for the following 4 months. Circulating levels of glucose, insulin, prolactin, testosterone, oestradiol, gonadotropins, sex hormone‐binding globulin adrenocorticotropic hormone, insulin‐like growth factor‐1, thyrotropin and free thyroid hormones were measured at the beginning and at the end of the study. Although metformin reduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels. Only in patients with abnormally low testosterone levels, the drug decreased prolactin levels. This effect, which was accompanied by an increase in luteinizing hormone levels, was inversely correlated with baseline testosterone and calculated free testosterone levels, and positively with treatment‐induced improvement in insulin sensitivity. In both treatment groups, metformin produced a neutral effect on plasma levels of the remaining hormones. The obtained results suggest that endogenous testosterone may attenuate the impact of metformin on lactotropic cells.     

Knockout model reveals the role of Nischarin in mammary gland development,breast tumorigenesis and response to metformin treatment

Previously, our lab discovered the protein Nischarin and uncovered its role in regulating cell migration and invasion via its interactions with several proteins. We subsequently described a role for Nischarin in breast cancer, in which it is frequently underexpressed. To characterize Nischarin's role in breast tumorigenesis and mammary gland development more completely, we deleted a critical region of the Nisch gene (exons 7–10) from the mouse genome and observed the effects. Mammary glands in mutant animals showed delayed terminal end bud formation but did not develop breast tumors spontaneously. Therefore, we interbred the animals with transgenic mice expressing the mouse mammary tumor virus-polyoma middle T-antigen (MMTV-PyMT) oncogene. The MMTV-PyMT mammary glands lacking Nischarin showed increased hyperplasia compared to wild-type animal tissues. Furthermore, we observed significantly increased tumor growth and metastasis in Nischarin mutant animals. Surprisingly, Nischarin deletion decreased activity of AMPK and subsequently its downstream effectors. Given this finding, we treated these animals with metformin, which enhances AMPK activity. Here, we show for the first time, metformin activates AMPK signaling and inhibits tumor growth of Nischarin lacking PyMT tumors suggesting a potential use for metformin as a cancer therapeutic, particularly in the case of Nischarin-deficient breast cancers.     

Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation

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