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101.
Takashige Kawakami Kaori NishiyamaYoshito Kadota Masao SatoMasahisa Inoue Shinya Suzuki 《Toxicology and applied pharmacology》2013
Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT−/−) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT+/+) mice. Cd administration more significantly reduced the adipocyte size of MT−/− mice than that of MT+/+ mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT−/− mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. 相似文献
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《药学学报(英文版)》2020,10(8):1347-1359
Gene therapy is rapidly emerging as a powerful therapeutic strategy for a wide range of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Some early clinical trials have failed to achieve satisfactory therapeutic effects. Efforts to enhance effectiveness are now concentrating on three major fields: identification of new vectors, novel therapeutic targets, and reliable of delivery routes for transgenes. These approaches are being assessed closely in preclinical and clinical trials, which may ultimately provide powerful treatments for patients. Here, we discuss advances and challenges of gene therapy for neurodegenerative disorders, highlighting promising technologies, targets, and future prospects. 相似文献
104.
Liver disease is a global health problem and is a primary cause of mortality and morbidity worldwide. Specifically, it accounts for approximately two million deaths per year worldwide. The common causes of mortality are the complications of liver cirrhosis, viral hepatitis and hepatocellular carcinoma (HCC). The mechanism of immune response and infiltration of cellular immunity is essential for promoting hepatic inflammatory, especially when the liver is abundant with lymphocytes and phagocytic cells. The injured and immunity cells secret different types of interleukins (cytokines), which can directly or indirectly amplify or inhibit liver inflammation. Many types of cells can produce interleukin-34 (IL-34) that induces the release of multiple inflammatory factors in patients via interaction with various cytokines. This phenomenon leads to the enlargement of the inflammatory response to liver diseases and induces liver fibrosis. This review highlights the proposed roles of IL-34 in liver diseases and discusses the recent findings of IL-34 that support its emerging role in HCC. Specifically, the facilitating effects of these new insights on the rational development of IL-34 for targeted therapies in the future are explored. 相似文献
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Guy Laureys Ralph Clinckers Sarah Gerlo Anneleen Spooren Nadine Wilczak Ron Kooijman Ilse Smolders Yvette Michotte Jacques De Keyser 《Progress in neurobiology》2010
Evidence accumulates for a key role of the β2-adrenergic receptors in the many homeostatic and neuroprotective functions of astrocytes, including glycogen metabolism, regulation of immune responses, release of neurotrophic factors, and the astrogliosis that occurs in response to neuronal injury. A dysregulation of the astrocytic β2-adrenergic-pathway is suspected to contribute to the physiopathology of a number of prevalent and devastating neurological conditions such as multiple sclerosis, Alzheimer's disease, human immunodeficiency virus encephalitis, stroke and hepatic encephalopathy. In this review we focus on the physiological functions of astrocytic β2-adrenergic receptors, and their possible impact in disease states. 相似文献
108.
E. Courty P. Gobalakichenane M. Garcia A. Muscat C. Kazakian T. Ledent M. Moldes B. Blondeau D. Mitanchez M. Buyse B. Fève 《Diabetes & metabolism》2018,44(3):281-291
Second-generation antipsychotics (SGAs) are well known for their metabolic side effects in humans, including obesity and diabetes. These compounds are maintained during pregnancy to prevent the relapse of psychoses, but they readily diffuse across the placenta to the fetus, as documented with the widely-prescribed drug olanzapine (OLZ). However, observational studies have provided conflicting results on the potential impact of SGAs on fetal growth and body weight, and their effects on metabolic regulation in the offspring. For this reason, our study has tested whether antenatal exposure of CD1 mice to OLZ influenced metabolic outcomes in the offspring of the first (F1) and second (F2) generations. In F1 mice, OLZ antenatal treatment caused a decrease in neonatal body weight in both genders, an effect that persisted throughout life only in male animals. Interestingly, F1 female mice also displayed altered glucose homoeostasis. F2 mice, generated by mating normal males with F1 female mice exposed to OLZ during antenatal life, exhibited higher neonatal body weights which persisted only in F2 female animals. This was associated with expansion of fat mass and a concordant pattern of adipose tissue gene expression. Moreover, male and female F2 mice were glucose-intolerant. Thus, our study has demonstrated that antenatal OLZ exposure induces multigenerational and gender-specific programming of glucose tolerance in the offspring mice as adults, and points to the need for careful monitoring of children exposed to SGAs during pregnancy. 相似文献
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Ning Ma Ning Xu Dong Yin Ping Zheng Weiwei Liu Guofeng Wang Yuan Hui Guanjun Han Chuanhui Yang Xingbo Cheng 《Medicine》2021,100(33)
The current study aimed to investigate circulating glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in Chinese type 2 diabetes mellitus (T2DM) patients, especially those with microalbuminuria. We recruited 67 patients with T2DM and 63 control subjects. We determined circulating GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Compared with control groups, patients with T2DM showed decreased circulating levels of GRP78 (0.21 [0.16–0.24] vs 0.16 [0.16–0.19] ng/mL, P < .01) and CHOP ([0.29 ± 0.02] vs [0.27 ± 0.03]ng/mL, P < .01). Reduction in circulating GRP78 and CHOP levels was more pronounced in patients with more severe categories of albuminuria. Amounts of circulating GRP78 correlated directly with serum fasting c-peptide, cystatin-c (Cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Circulating CHOP level was positively correlated with age, Cr, BUN, Cys-c, and urinary microalbumin/creatinine (UmALB/Cr). Circulating GRP78 was predicted independently by Cr, BUN, serum uric acid, estimated glomerular filtration rate, and Cys-c, while CHOP depended on age, Cr, BUN, estimated glomerular filtration rate, UmALB/Cr, and Cys-c. After controlling for confounding factors, circulating GRP78 and CHOP expression were significantly associated with diabetic kidney disease (binary logistic regression, P < .01). Patients with T2DM showed increased circulating GRP78 and CHOP concentrations. Receiver operating characteristic areas under the curve for predicting diabetic kidney disease based on GRP78 and CHOP were 0.686 (95% CI: 0.558–0.813) and 0.670 (0.524–0.816), respectively. 相似文献