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Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.
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Disturbance of the energy balance, when the energy intake exceeds its expenditure, is a major risk factor for the development of metabolic syndrome (MS). The peroxisome proliferator activated receptor γ (PPARγ) coactivator-1α (PGC-1α) functions as a key regulator of energy metabolism and has become a hotspot in current researches. PGC-1α sensitively responds to the environmental stimuli and nutrient signals, and further selectively binds to different transcription factors to regulate various physiological processes, including glucose metabolism, lipid metabolism, and circadian clock. In this review, we described the gene and protein structure of PGC-1α, and reviewed its tissue-specific function in the regulation of energy homeostasis in various mammalian metabolic organs, including liver, skeletal muscle and heart, etc. At the meanwhile, we summarized the application of potential small molecule compounds targeting PGC-1α in the treatment of metabolic diseases. This review will provide theoretical basis and potential drug targets for the treatment of metabolic diseases.
Subject(s)
Animals , Energy Metabolism , Homeostasis , Lipid Metabolism , Liver/metabolism , Muscle, Skeletal/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Transcription Factors/metabolismABSTRACT
Not only should a series of special physiological changes that occur in pregnant women be considerated,but the effects of anesthesia drugs on the fetus should also be considered,in order to conduct a simple,safe,and effective anesthesia in cesarean section surgery.This review will summarize the current selection of anesthesia approachs for cesarean section and the prevention and control of common anesthesia accidents and complications,aiming at guiding the clinical practice,reducing the risk of cesarean section anesthesia,ensuring the maternal and fetal safety and achieving comfort in diagnostic and therapeutic procedure.
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Pregnancy with heart disease is one of the serious complications of obstetric diseases,which is the main cause of maternal and neonatal death in perioperative period.The choice of anesthesia for pregnancy with heart disease is mainly based on the condition of the mother and the condition of the fetus in the uterus.Regardless of the choice of anesthesia,the maternal vital signs should be stabilized and the safety of the newborn is the most important thing.This article describes these contents,with a view to guide clinical practice and achieve safe anesthesia.
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Objective:To observe the effect of astragalus polysaccharide (APS) on taste receptor 1 member 2 (T1R2)/taste receptor 1 member 3 (T1R3) sweet taste receptor pathway in intestine of rat model induced by high-sugar and high-fat diet. Method:SD rats were randomly divided into normal group, high-sugar and high-fat group and astragalus polysaccharide group. Rats in high-sugar and high-fat group and astragalus polysaccharide groups were fed with high-sugar and high-fat diet for 16 weeks, while rats in astragalus polysaccharide group were fed with APS (0.7 g·kg-1, per day) for 8 weeks during this period. Serum samples were collected to determine the levels of fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Intestinum tenue was collected to determine mRNA expressions of T1R2/T1R3, α-gustducin (Gα gust), transient receptor potential cation channel subfamily member 5 (TRPM5) and proglucagon (PG) gene by Real-time PCR, and protein expressions of T1R2, Gα gust and glucagon-like peptide-1 (GLP-1) protein by Western blot. Result:Rats in high-sugar and high-fat group had significantly higher levels of TC, TG and LDL-C, and lower HDL-C level in serum than those in normal group (Pα gust and PG genes in intestine, were significantly down-regulated in high-sugar and high-fat group (PPα gust, TRPM5 and PG genes in intestine were significantly up-regulated in astragalus polysaccharide group (Pα gust and GLP-1 protein expressions was consistent with that of T1R2, Gα gust and GLP-1 mRNA expressions. Protein expressions of T1R2, Gα gust and GLP-1 and mRNA expression of T1R3 were significantly lower in astragalus polysaccharide group than those of control group (PConclusion:APS could improve disturbance of lipid metabolism and impairment of intestinal sweet taste receptor pathway for rat model induced by high-sugar and high-fat diet.
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<p><b>OBJECTIVE</b>This study aims to understand the current status and analyze the influencing factors of tooth extraction anxiety of dental patients.</p><p><b>METHODS</b>The General Factor Questionnaire and Modified Dental Anxiety Scale (MDAS) were used to survey and analyze tooth extraction anxiety of 800 dental patients. Single-factor and multi-factor analyses were used for statistical data analysis.</p><p><b>RESULTS</b>A total of 768 qualified questionnaires were received out of 800, the efficiency was 96%. The mean MDAS score was 10.21±3.29. The prevalence percentage of dental anxiety was 14.7%. Significant statistical differences of the incidence of dental anxiety were observed with regard to sex, age, tooth extraction time, accompanying relatives and friends, before tooth extraction, tooth extraction experience for family and friends, pain tolerance, mental health state before tooth extraction, and self-reported oral health status (P<0.05. By contrast, no significant statistical differences in the incidence of dental anxiety were observed with regard to educational level, tooth extraction type, national life experience, profession, and personality (P>0.05). Logistic regression analysis indicated that the risk factors of dental anxiety were sex, accompanying relatives and friends, mental health state before tooth extraction, and self-rated oral health status.</p><p><b>CONCLUSIONS</b>The prevalence percentage of tooth extraction anxiety is high for dental patients. Gender, age, health satisfaction, tooth extraction time, accompanying relatives and friends, before tooth extraction, tooth extraction experience for family and friends, pain tolerance, mental health state before tooth extraction, and self-reported oral health status are the influencing factors of dental anxiety.</p>
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AIM To determine the quality constant of Chinese medicine and to establish a method of grades evaluation of Cortex Moutan decoction pieces.METHODS Cortex Moutan decoction pieces' morphological indexes should be observed and measured,the contents of phenol and paeoniflorin were measured by HPLC.Cortex Moutan decoction pieces was graded according to the quality constant of Chinese medicine which was calculated.RESULTS Cortex Moutan decoction pieces could be divided into three grades by the quality constant of Chinese medicine,the cutoff point of the firsts was greater than or equal to 1.56;the second was greater than or equal to 1.12 but less than 1.56;while the third was less than 1.12.CONCLUSION This method combines the apparent parameters of Cortex Moutan decoction pieces with its intrinsic quality,which can devide grades of it objectively and provides a reference for its classification.
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Mammals synchronize their circadian activity primarily to the cycles of light and darkness in the environment. Circadian rhythm is controlled by the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and the peripheral clocks in various tissues. More importantly, the central clock can integrate photic/nonphotic signals to generate rhythmic outputs, and then drive the slave oscillators in peripheral tissues through neuroendocrine and behavioral signals. Human reproductive activities, as some other physiological functions, are controlled by the biological clocks. Accumulating lines of epidemiological and genetic evidence indicate that disruption of circadian clock can be directly involved in multiple pathological processes, including infertility. In this review, we mainly discuss the presence of a circadian clock in reproductive tissues and its roles in follicles development, ovulation, spermatogenesis, fertilization and embryo implantation, etc. As the increased shift work and assisted reproductive technologies possibly disrupt circadian rhythmicity to impact reproduction, the importance of circadian rhythms should be highlighted in the regulation of reproductive process.
Subject(s)
Animals , Biological Clocks , Circadian Rhythm , Hypothalamus , Light , Reproduction , Suprachiasmatic NucleusABSTRACT
Oridonin, a diterpenoid isolated from Rabdosia rubescens, has been proven to possess various pharmacological and physiological effects such as anti-inflammation, anti-bacterial, and anti-neoplastic, although in recent years, more attention has been paid to its anti-neoplastic effects. For example, oridonin can trigger cell cycle arrest, apoptosis, and autophagy in different neoplastic cell lines. This review summarizes the considerable knowledge about the action mechanisms of oridonin that has been studied in recent years. The present observations reveal the novel anti-neoplastic effects of oridonin, suggesting that it may be effective as a potent alternative or adjunct drug to conventional chemotherapy.
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Animals , Humans , Antineoplastic Agents , Chemistry , Pharmacology , Therapeutic Uses , Apoptosis , Cell Cycle , Diterpenes, Kaurane , Chemistry , Pharmacology , Therapeutic Uses , Neoplasms , Drug Therapy , Pathology , Signal TransductionABSTRACT
Signal transduction in cells plays an important role in the process of cellular metabolism, segmentation, differentiation, biological behaviors and cell death. Direct and indirect involvement of kinases in tumor growth, metastasis and apoptosis make them the most promising targets for anticancer discovery. Most of the kinase inhibitors in clinical use or in late development stages are multi-target kinase inhibitors (MTKIs). These MTKIs are demonstrated to exert potent anti-tumor effects through several different pathways. This review presents in the view of a medicinal chemistry point, a brief account and analysis of transduction pathways of representative MTKIs in clinical use or in late development stages.
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Humans , Antineoplastic Agents , Therapeutic Uses , Clinical Trials, Phase III as Topic , Drug Delivery Systems , Methods , Neoplasms , Drug Therapy , Protein Kinase Inhibitors , Therapeutic Uses , Signal TransductionABSTRACT
To investigate the potential role and the mechanism of PLZF-RARalpha/RARalpha-PLZF double fusion gene in the pathogenesis of acute promyelocytic leukemia (APL) in vivo at systematic biological level, PLZF-RARalpha/RARalpha-PLZF double transgenic mouse model was established by intercross; the integration and expression of fusion genes were analyzed by PCR and RT-PCR; the disease phenotype was detected by morphological and pathological examination of peripheral blood and bone marrow cells, as well as flow cytometry assays; the effects of ATRA with or without tricostatin A on bone marrow blast cells from PLZF-RARalpha/RARalpha-PLZF double TM were observed. The results showed that leukemia occurred in 5 PLZF-RARalpha/RARalpha-PLZF double TM 7, 7, 9, 11 and 11 months respectively, out of them two (40%) with classic APL features, the others (60%) with chronic myeloid leukemia through an observation period of 18 months. The leukemia occurrence of PLZF-RARalpha/RARalpha-PLZF TM was about 10%, which was similar to PLZF-RARalpha TM as that reported before. The latency was over 6 months, not earlier than PLZF-RARalpha TM only. No morphologic changes of PLZF-RARalpha/RARalpha-PLZF double TM blast cells to ATRA were observed, but increased cytoplasmic-nuclear ratio and nuclear condensation in bone marrow blast cells were found in combination of ATRA with tricostatin A. It is concluded that PLZF-RARalpha/RARalpha-PLZF double fusion gene transgenic mice have heterogeneity of pathogenesis. HDAC inhibitors such as trichostatin A, in combination with ATRA, induce differentiation of the blast/promyelocytic cells from PLZF-RARa/RARa-PLZF double TM, but not ATRA alone.
Subject(s)
Animals , Female , Humans , Male , Mice , Antigens, CD34 , Blood , Bone Marrow Cells , Allergy and Immunology , Pathology , Cell Differentiation , Chorionic Gonadotropin , Genetics , Disease Models, Animal , Flow Cytometry , Hydroxamic Acids , Pharmacology , Leukemia, Promyelocytic, Acute , Blood , Genetics , Pathology , Mice, Inbred C57BL , Mice, Inbred CBA , Mice, Transgenic , Oncogene Proteins, Fusion , Genetics , Pedigree , Receptors, Chemokine , Blood , Tretinoin , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To acquire a deep understanding of the possible mechanisms of realgar in the treatment of acute promyelocytic leukemia (APL).</p><p><b>METHOD</b>All-trans retinoic acid (ATRA) resistant APL cell line MR2 was used as in vitro model. The effect of realgar on MR2 cell was observed by watching cell viability, cell growth, and by using Methy thiazolyl tetrazolium (MTT) assay, cell morphology, DNA gel electrophoresis and flow cytometry assay.</p><p><b>RESULT</b>The viability and growth of MR2 cell were inhibited after the treatment, to some extent, in a dose and time dependent manner. After being treated with realgar, MR2 cell presented morphologically some features of apoptotic cells such as intact cell membrane, chromatin condensation and nuclear fragmentation, and apoptotic body could be found by electron microscopy as well. Sub-G1 cells were observed by flow cytometry, as well as Annexin V FITC+/PI-cells. DNA ladder could be found by DNA gel electrophoresis.</p><p><b>CONCLUSION</b>Realgar can induce apoptosis of ATRA resistant APL cell line MR2, Which shows the therapeutic effect of realgar on APL may be different from that of ATRA.</p>