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排序方式: 共有321条查询结果,搜索用时 156 毫秒
81.
82.
Andrea Tagliapietra John Charles Rotondo Ilaria Bononi Elisa Mazzoni Federica Magagnoli Lucia Oton Gonzalez Carlo Contini Fortunato Vesce Mauro Tognon Fernanda Martini 《Journal of cellular physiology》2020,235(3):1888-1894
Droplet-digital polymerase chain reaction (ddPCR) technique was set up to detect/quantify Merkel cell polyomavirus (MCPyV) DNA in clinical specimens, including chorionic villi and peripheral blood mononuclear cells (PBMCs) from spontaneous abortion (SA)-affected females. This ddPCR assay showed high accuracy, sensitivity, and specificity in detecting MCPyV DNA cloned in a recombinant plasmid vector, the control. ddPCR was extended to MCPyV DNA to investigate/quantify its sequences in clinical samples. Overall, 400 samples were analyzed, that is, 100 chorionic villi and 100 PBMCs, from SA females (n = 100), the cases, and 100 chorionic villi and 100 PBMCs from females who underwent voluntary pregnancy interruption (VI, n = 100), the control. MCPyV DNA was detected in 4/100 (4%) and 5/100 (5%) of SA and VI chorionic villi, respectively. The mean viral DNA load was 1.99 ( ± 0.94 standard mean deviation [SD]) copy/104 cells in SA and 3.02 ( ± 1.86 [SD]) copy/104 cells in VI. In PBMCs, MCPyV DNA was revealed in 9/100 (9%) and 14/100 (14%) of SA and VI, with a mean of 2.09 ( ± 1.17 [SD]) copy/104 cells and 4.09 ( ± 4.26 [SD]) copy/104 cells in SA and VI, respectively. MCPyV gene expression analysis by quantitative PCR for the large T antigen (LT) and viral capsid protein 1 (VP1) showed their mRNAs in 2/4 (50%) SA- and 2/5 (40%) VI-MCPyV-positive samples. MCPyV DNA was detected/quantified using the ddPCR technique, in chorionic villi and PBMCs from SA and VI. In our experimental conditions, ddPCR provided a powerful tool to detect/quantify MCPyV DNA sequences in clinical samples. 相似文献
83.
Xiaohui Wang Zhuyao Wang Yuzhen YaoJingjin Li Xiaojin ZhangChuanfu Li Yunlin ChengGuoxian Ding Li Liu Zhengnian Ding 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2011,1813(5):827-838
Background
Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. Alpha-lipoic acid (LA) has been used as a therapeutic approach for a variety of neural disorders. We recently reported that LA prevents local anesthetics-induced neurite loss. In this study, we hypothesized that LA administration promotes neurite outgrowth.Methods
To test our hypothesis, we treated mouse neuroblastoma N2a cells and primary neurons with LA. Neurite outgrowth was evaluated by examination of morphological changes and by immunocytochemistry for β-tubulin-3. ROS production was examined, as were the phosphorylation levels of ERK and Akt. In separate experiments, we determined the effects of the inhibition of ERK or PI3K/Akt as well as ROS production on LA-induced neurite outgrowth.Results
LA promoted significantly neurite outgrowth in a time- and concentration-dependent manner. LA stimulation significantly increased the phosphorylation levels of both Akt and ERK and transiently induced ROS production. PI3K/Akt inhibition did not affect LA-induced neurite outgrowth. However, the inhibition of ERK activation completely abolished LA-induced neurite outgrowth. Importantly, the prevention of ROS production by antioxidants attenuated LA-stimulated ERK activation and completely abolished LA-promoted neurite outgrowth.Conclusion
Our data suggest that LA stimulates neurite outgrowth through the activation of ERK signaling, an effect mediated through a ROS-dependent mechanism. 相似文献84.
Ayala C Valdez SR Morero ML Soaje M Carreño NB Sanchez MS Bittencourt JC Jahn GA Celis ME 《Peptides》2011,32(6):1249-1254
To date, there has been only one in vitro study of the relationship between neuropeptide EI (NEI) and the hypothalamic-pituitary-thyroid (HPT) axis. To investigate the possible relationship between NEI and the HPT axis, we developed a rat model of hypothyroidism and hyperthyroidism that allows us to determine whether NEI content is altered in selected brain areas after treatment, as well as whether such alterations are related to the time of day. Hypothyroidism and hyperthyroidism, induced in male rats, with 6-propyl-1-thiouracil and l-thyroxine, respectively, were confirmed by determination of triiodothyronine, total thyroxine, and thyrotropin levels. All groups were studied at the morning and the afternoon. In rats with hypothyroidism, NEI concentration, evaluated on postinduction days 7 and 24, was unchanged or slightly elevated on day 7 but was decreased on day 24. In rats with hyperthyroidism, NEI content, which was evaluated after 4 days of l-thyroxine administration, was slightly elevated, principally in the preoptic area in the morning and in the median eminence-arcuate nucleus and pineal gland in the afternoon, the morning and afternoon NEI contents being similar in the controls. These results provide the bases to pursue the study of the interaction between NEI and the HPT axis. 相似文献
85.
Follicular thyroglobulin (TG) reflects the storage of both iodine and thyroid hormone. This is because it is a macromolecular precursor of thyroid hormone and organic iodinated compound in follicular lumen. Thus, it may have an important feedback role in thyroid function. In this study, monolayer cells were cultured and follicles were reconstituted with primary pig thyroid cells in vitro. Reconstituted follicles were treated with iodine and methimazole (MMI), a drug that blocks iodine organification and reduces the degree of TG iodination in follicular lumen. The high degree of iodinated TG in follicular lumen was observed to inhibit thyroid-restricted gene expression. To confirm this finding, monolayer thyroid cells were treated with a different degree of TG iodination at the same concentration. These iodinated TG were extracted from reconstituted follicles of different groups. In this manner, this study provides firsthand evidence suggesting that follicular TG inhibits the expressions of thyroid-restricted genes NIS, TPO, TG, and TSHr. 相似文献
86.
An increasing number of proteins are currently available on the market as therapeutics and this branch of the pharmaceutical industry will expand substantially during the coming years. As many diseases result from dysfunction of proteins forming multicomponent complexes, protein drugs with their inherent high specificity and affinity seem to be optimal medical agents. On the other hand, proteins are often highly instable and sensitive to degradation, which questions their applicability as effective therapeutics. Therefore, redesign and engineering of proteins is usually a required step in the present day drug development.Several approaches have been applied to optimize the protein properties central to their pharmaceutical use. This review focuses on different strategies that improve two crucial factors influencing protein drug efficiency: protein stability and its in vivo half-life. We provide examples of successful genetic and chemical modifications applied in the design of effective protein therapeutics. 相似文献
87.
88.
Hypothalamic neuronal histamine mediates the thyrotropin-releasing hormone-induced suppression of food intake 总被引:1,自引:0,他引:1
Gotoh K Fukagawa K Fukagawa T Noguchi H Kakuma T Sakata T Yoshimatsu H 《Journal of neurochemistry》2007,103(3):1102-1110
We examined the involvement of thyrotropin-releasing hormone (TRH) and TRH type 1 and 2 receptors (TRH-R1 and TRH-R2, respectively) in the regulation of hypothalamic neuronal histamine. Infusion of 100 nmol TRH into the rat third cerebroventricle (3vt) significantly decreased food intake (p < 0.05) compared to controls infused with phosphate- buffered saline. This TRH-induced suppression of food intake was attenuated partially in histamine-depleted rats pre-treated with alpha-fluoromethylhistidine (a specific suicide inhibitor of histidine decarboxylase) and in mice with targeted disruption of histamine H1 receptors. Infusion of TRH into the 3vt increased histamine turnover as assessed by pargyline-induced accumulation of tele-methylhistamine (t-MH, a major metabolite of neuronal histamine in the brain) in the tuberomammillary nucleus (TMN), the paraventricular nucleus, and the ventromedial hypothalamic nucleus in rats. In addition, TRH-induced decrease of food intake and increase of histamine turnover were in a dose-dependent manner. Microinfusion of TRH into the TMN increased t-MH content, histidine decarboxylase (HDC) activity and expression of HDC mRNA in the TMN. Immunohistochemical analysis revealed that TRH-R2, but not TRH-R1, was expressed within the cell bodies of histaminergic neurons in the TMN of rats. These results indicate that hypothalamic neuronal histamine mediates the TRH-induced suppression of feeding behavior. 相似文献
89.
Blanchard V Gadkari RA Gerwig GJ Leeflang BR Dighe RR Kamerling JP 《Glycoconjugate journal》2007,24(1):33-47
Human chorionic gonadotropin (hCG) is a heterodimeric, placental glycoprotein hormone involved in the maintenance of the corpus
luteum during the first trimester of pregnancy. Biologically active hCG has been successfully expressed in the yeast Pichia pastoris (phCG). In the context of structural studies and therapeutic applications of phCG, detailed information about its glycosylation
pattern is a prerequisite. To this end N-glycans were released with peptide-N
4-(N-acetyl-β-glucosaminyl)asparagine amidase F and fractionated via anion-exchange chromatography (Resource Q) yielding both
neutral (80%) and charged, phosphate-containing (20%) high-mannose-type structures. Subfractionations were carried out via
normal phase (Lichrosorb-NH2) and high-pH anion-exchange (CarboPac PA-1) chromatography. Structural analyses of the released N-glycans were carried out
by using HPLC profiling of fluorescent 2-aminobenzamide derivatives, MALDI-TOF mass spectrometry, and 500-MHz 1H-NMR spectroscopy. Detailed neutral oligosaccharide structures, in the range of Man8GlcNAc2 to Man11GlcNAc2 including molecular isomers, could be established, and structures up to Man15GlcNAc2 were indicated. Phosphate-containing oligosaccharides ranged from Man9
PGlcNAc2 to Man13
PGlcNAc2. Mannosyl O-glycans were not detected. Profiling studies carried out on different production batches showed that the oligosaccharide
structures are similar, but their relative amounts varied with the culturing media. 相似文献
90.
Formation of new blood vessels (angiogenesis) has been demonstrated to be a basic prerequisite for sustainable growth and proliferation of tumor. Several growth factors, cytokines, small peptides and enzymes support tumor growth either independently or in synergy. Decoding the crucial mechanisms of angiogenesis in physiological and pathological state has remained a subject of intense interest during the past three decades. Currently, the most widely preferred approach for arresting tumor angiogenesis is the blockade of vascular endothelial growth factor (VEGF) pathway; however, the clinical usage of this modality is still limited by several factors such as adverse effects, toxicity, acquired drug resistance, and non-availability of valid biomarkers. Nevertheless, angiogenesis, being a normal physiological process imposes limitations in maneuvering it as therapeutic target for tumor angiogenesis. The present review offers an updated relevant literature describing the role of well-characterized angiogenic factors, such as VEGF, basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), placenta growth factor (PLGF), hepatocyte growth factor/scatter factor (HGF/SF) and angiopoetins (ANGs) in regulating tumor angiogenesis. We have also attempted to discuss tumor angiogenesis with a perspective of ‘an attractive target with emerging challenges’, along with the limitations and present status of anti-angiogenic therapy in the current state-of-the-art. 相似文献