RÉSUMÉ
INTRODUCTION: This study investigated gender differences in the reading behaviors of Chinese middle school students, and whether gender stereotypes relating to choices of reading matter are supported. METHODS: A mixed-methods approach was adopted. Three thousand nine hundred and fifteen middle school (Grade 7) students completed a questionnaire designed to assess reading behaviors. Independent sample t-test and chi-square analyses were employed to examine gender differences in reading behaviors. The qualitative survey was supplemented with an open response survey (94 boys, 50 girls), which provided further insights into individuals' specific experiences and perspectives regarding reading behaviors and gender stereotypes in reading choices. RESULTS: This study revealed a number of gender-linked differences. Boys spent more time reading than girls but read the same number of books; boys were also more likely than girls to read digital texts, while girls were more likely to borrow their reading material. Choice of subject matter also differed: boys were more likely to read factual and action-based books, while girls' choices focused more on motives and emotions. Another significant difference was that boys paid more attention to the overall experience of reading, while girls paid more attention to the details of reading. Responses to the open response survey indicated that gender stereotypes in reading choices were prevalent among respondents, but some students' reading choices did not align with the stereotype associated with their gender. CONCLUSION: The mixed-methods approach proved valuable in both identifying gender differences in reading behaviors, and in highlighting the prevalence of gender stereotypes in reading choices among middle school students.
Sujet(s)
Livres , Lecture , Stéréotypes , Étudiants , Humains , Mâle , Femelle , Adolescent , Chine , Facteurs sexuels , Enquêtes et questionnaires , Étudiants/psychologie , Étudiants/statistiques et données numériques , Enfant , Peuples d'Asie de l'EstRÉSUMÉ
In recent years, Flammulina velutipes (F. velutipes) has attracted consequential attention in various research fields due to its rich composition of proteins, vitamins, amino acids, polysaccharides, and polyphenols. F. velutipes polysaccharides (FVPs) are considered as key bioactive components of F. velutipes, demonstrating multiple physiological activities, including immunomodulatory, anti-inflammatory, and antibacterial properties. Moreover, they offer health benefits such as antioxidant and anti-aging properties, which have exceptionally valuable clinical applications. Polysaccharides derived from different sources exhibit a wide range of biomedical functions and distinct biological activities. The varied biological functions of polysaccharides, coupled with their extensive application in functional foods and clinical applications, have prompted a heightened focus on polysaccharide research. Additionally, the extraction, deproteinization, and purification of FVPs are fundamental to investigate the structure and biological activities of polysaccharides. Therefore, this review provides a comprehensive and systematic overview of the extraction, deproteinization, purification, characterization, and structural elucidation of FVPs. Furthermore, the biological activities and mechanisms of FVPs have been further explored through in vivo and in vitro experiments. This review aims to provide a theoretical foundation and guide future research and development of FVPs.
Sujet(s)
Flammulina , Polysaccharides fongiques , Animaux , Humains , Antibactériens/pharmacologie , Antibactériens/composition chimique , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/composition chimique , Antioxydants/pharmacologie , Antioxydants/composition chimique , Flammulina/composition chimique , Polysaccharides fongiques/composition chimique , Polysaccharides fongiques/pharmacologie , Facteurs immunologiques/pharmacologie , Facteurs immunologiques/composition chimiqueRÉSUMÉ
The incidence and mortality of breast cancer, the most common malignant tumor among women in the world, are increasing year by year, which greatly threatens women's health. Ferroptosis is an iron and lipid reactive oxygen species (ROS)-dependent process, a novel form of cell death that is distinct from apoptosis and is closely related to the progression of breast cancer. Inducing the occurrence of ferroptosis in tumor cells can effectively block its malignant progress in vivo. Oridonin (ORI), the primary active ingredient extracted from the Chinese herbal medicine Rabdosia rubescens, has been shown to cause glutathione depletion and directly inhibit glutathione peroxidase 4 induced cell death by ferroptosis, but its mechanism of action in breast cancer remains inadequately elucidated. Therefore, we further investigated whether ORI could promote RSL3-induced ferroptosis in breast cancer cells by regulating the oxidative stress pathway JNK/Nrf2/HO-1. In our study, we assessed cell survival of RSL3 and ORI treatment by MTT assay, and found that co-treatment with RSL3 and ORI inhibited cell proliferation, as evidenced by the cloning assay. To investigate the ability of ORI to promote RSL3-induced ferroptosis in breast cancer cells, we measured levels of ROS, malondialdehyde, glutathione, superoxide dismutase, and Fe2+ content. Lipid peroxidation, ROS, and mitochondrial membrane potential levels induced by co-treatment of ORI with RSL3 were reversed by ferrostatin-1, further confirming that the cell death induced by RSL3 and ORI was ferroptosis rather than other programmed cell death modes. Moreover, RSL3 and ORI co-treatment regulated the JNK/Nrf2/HO-1 axis, as demonstrated by western blotting and target activator validation. Our results showed that ORI could enhance the inhibitory effect of RSL3 on breast cancer cells viability via the induction of ferroptosis. Mechanistically, it potentiated RSL3-induced ferroptosis in breast cancer cells by activating the JNK/Nrf2/HO-1 axis. This study provides a theoretical basis for the application of ORI based on the mechanism of ferroptosis, and provides potential natural drug candidates for cancer prevention and treatment.
Sujet(s)
Tumeurs du sein , Diterpènes de type kaurane , Ferroptose , Heme oxygenase-1 , Facteur-2 apparenté à NF-E2 , Stress oxydatif , Ferroptose/effets des médicaments et des substances chimiques , Humains , Facteur-2 apparenté à NF-E2/métabolisme , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Tumeurs du sein/traitement médicamenteux , Stress oxydatif/effets des médicaments et des substances chimiques , Heme oxygenase-1/métabolisme , Diterpènes de type kaurane/pharmacologie , Femelle , Transduction du signal/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale , Espèces réactives de l'oxygène/métabolisme , Survie cellulaire/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , JNK Mitogen-Activated Protein Kinases/métabolisme , Cellules MCF-7 , Système de signalisation des MAP kinases/effets des médicaments et des substances chimiques , CarbolinesRÉSUMÉ
Selenium, an essential trace element of the human body, is pivotal in human health and disease prevention. Nevertheless, the narrow therapeutic index of selenium, where the toxic and therapeutic doses are close, limits its clinical utility. Significantly, nanoscale selenium synthesized by different methods using polysaccharides as stabilizers has low toxicity properties and exhibits excellent bioactivity. Its biological activities, such as anti-tumor, anti-inflammatory, antioxidant, antibacterial, and immune function enhancement, are improved compared with traditional organic and inorganic selenium compounds, conferring greater potential for application in biomedicine. Therefore, this review evaluates the advancements in various synthesis methodologies for polysaccharide selenium nanoparticles (Se NPs) and their biological activities. It aims to provide a comprehensive theoretical basis and research directions for the future development of highly efficient, minimally toxic, and biocompatible polysaccharide-Se NPs and the application of polysaccharide-Se NPs in biomedicine.
Sujet(s)
Antioxydants , Nanoparticules , Polyosides , Sélénium , Sélénium/composition chimique , Sélénium/pharmacologie , Polyosides/composition chimique , Polyosides/pharmacologie , Polyosides/synthèse chimique , Humains , Nanoparticules/composition chimique , Antioxydants/pharmacologie , Antioxydants/composition chimique , Antioxydants/synthèse chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/synthèse chimique , Animaux , Antibactériens/pharmacologie , Antibactériens/composition chimique , Antibactériens/synthèse chimique , Anti-inflammatoires/composition chimique , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/synthèse chimiqueRÉSUMÉ
Numerous studies have shown that a low level of high-density lipoprotein cholesterol (HDL-C) is an independent biomarker of cardiovascular disease. High-density lipoprotein (HDL) is considered to be a protective factor for atherosclerosis (AS). Therefore, raising HDL-C has been widely recognized as a promising strategy to treat atherosclerotic cardiovascular diseases (ASCVD). However, several studies have found that increasing HDL-C levels does not necessarily reduce the risk of ASCVD. HDL particles are highly heterogeneous in structure, composition, and biological function. Moreover, HDL particles from atherosclerotic patients exhibit impaired anti-atherogenic functions and these dysfunctional HDL particles might even promote ASCVD. This makes it uncertain that HDL-raising therapy will prevent and treat ASCVD. It is necessary to comprehensively analyze the structure and function of HDL subfractions. We review current advances related to HDL subfractions remodeling and highlight how current lipid-modifying drugs such as niacin, statins, fibrates, and cholesteryl ester transfer protein inhibitors regulate cholesterol concentration of HDL and specific HDL subfractions.
Sujet(s)
Athérosclérose , Maladies cardiovasculaires , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase , Humains , Maladies cardiovasculaires/prévention et contrôle , Lipoprotéines HDL , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Cholestérol , Cholestérol HDL , Athérosclérose/traitement médicamenteux , Athérosclérose/prévention et contrôleRÉSUMÉ
The brain is the most cholesterol-rich organ in mammals. However, cholesterol metabolism in the brain is completely independent of other tissues due to the presence of the blood-brain barrier (BBB). Neurons, astrocytes and oligodendrocytes are the main cells responsible for cholesterol synthesis in the brain. The cholesterol content in the brain is maintained at a relatively constant level under strict regulation of synthesis, transport, and turnover, that is, brain cholesterol homeostasis. Once this balance is disrupted, neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) ensue. This review summarizes the processes controlling cholesterol homeostasis with respect to the synthesis, transport and turnover of cholesterol in the brain. We further focus on how cholesterol imbalance contributes to neurodegenerative diseases to explore the possibilities to modulate the key steps involved, which will provide clues for the development of therapies for the treatment of central nervous system (CNS) diseases.
Sujet(s)
Maladies neurodégénératives , Animaux , Maladies neurodégénératives/métabolisme , Encéphale/métabolisme , Barrière hémato-encéphalique/métabolisme , Cholestérol/métabolisme , Homéostasie , Mammifères/métabolismeRÉSUMÉ
In recent years, attention has increasingly focused on herbal medicines and their bioactive components attributed to their multi-target pharmacological activity and low side effects. Oridonin is a natural diterpenoid extracted from the traditional Chinese herb and is one of the main active components of Rabdosia rubescens. Modern pharmacological studies have shown that oridonin has anti-tumor, anti-bacterial, anti-inflammatory, anti-oxidant, cardiovascular protective, immunomodulatory, and other effects. Based on the published literature in recent years, we outline the pharmacological activities of oridonin, aiming to provide a theoretical basis for the design and development of new oridonin-based drugs, as well as to facilitate the process of oridonin for clinical use.
Sujet(s)
Antinéoplasiques , Diterpènes de type kaurane , Diterpènes , Tumeurs , Humains , Diterpènes de type kaurane/pharmacologie , Diterpènes de type kaurane/usage thérapeutique , Diterpènes/pharmacologie , Diterpènes/usage thérapeutique , Tumeurs/traitement médicamenteux , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/usage thérapeutique , Lignée cellulaire tumoraleRÉSUMÉ
BACKGROUND: Extralevator abdominoperineal excision (ELAPE) has been recommended for treating low rectal cancer due to its potential advantages in improving surgical safety and oncologic outcomes as compared to conventional abdominoperineal excision (APE). In ELAPE, however, whether the benefits of intraoperative position change to a prone jackknife position outweighs the associated risks remains controversial. This study is to introduce a modified position change in laparoscopic ELAPE and evaluate its feasibility, safety and the long-term therapeutic outcomes. METHODS: Medical records of 56 consecutive patients with low rectal cancer underwent laparoscopic ELAPE from November 2013 to September 2016 were retrospectively studied. In the operation, a perineal dissection in prone jackknife position was firstly performed and the laparoscopic procedure was then conducted in supine position. Patient characteristics, intraoperative and postoperative outcomes, pathologic and 5-year oncologic outcomes were analyzed. RESULTS: The mean operation time was 213.5 ± 29.4 min and the mean intraoperative blood loss was 152.7 ± 125.2 ml. All the tumors were totally resected, without intraoperative perforation, conversion to open surgery, postoperative 30-day death, and perioperative complications. All the patients achieved pelvic peritoneum reconstruction without the usage of biological mesh. During the follow-up period, perineal hernia was observed in 1 patient, impaired sexual function in 1 patient, and parastomal hernias in 3 patients. The local recurrence rate was 1.9% and distant metastasis was noted in 12 patients. The 5-year overall survival rate was 76.4% and the 5-year disease-free survival rate was 70.9%. CONCLUSIONS: Laparoscopic ELAPE with modified position change is a simplified, safe and feasible procedure with favorable outcomes. The pelvic peritoneum can be directly closed by the laparoscopic approach without the application of biological mesh.
Sujet(s)
Procédures de chirurgie digestive , Laparoscopie , Proctectomie , Tumeurs du rectum , Abdomen/anatomopathologie , Abdomen/chirurgie , Procédures de chirurgie digestive/effets indésirables , Humains , Laparoscopie/effets indésirables , Laparoscopie/méthodes , Périnée/chirurgie , Tumeurs du rectum/anatomopathologie , Tumeurs du rectum/chirurgie , Études rétrospectives , Résultat thérapeutiqueRÉSUMÉ
ABSTRACT: Inositol 1, 4, 5-trisphosphate (IP3) signaling-mediated calcium release drives the contraction of vascular smooth muscles and hence regulates blood vessel volume and blood pressure. Melatonin supplementation has been suggested to be beneficial for hypertension. To determine whether the blood pressure-lowering effect of melatonin was accounted for by IP3 signaling, we evaluated the vasoconstriction response and IP3 signaling in isolated mouse thoracic aortic rings during melatonin incubation. C57BL/6 mice were given intraperitoneal injections daily with melatonin, and the systolic blood pressure and contractility of aortic rings from melatonin-treated mice were decreased, and the contraction suppression effect of melatonin was attributed to the impaired expression of contractile proteins in vascular smooth muscle cells rather than IP3 signaling. Our results further showed that melatonin increased the expression of γ-secretase, which could cleave and release the notch intracellular domain, and the notch intracellular domain prevented the transcription of contractile genes by interfering with the interaction between serum response factor and myocardin, the master regulator of contractile protein. In this article, we report a novel mechanism by which melatonin regulates smooth muscle contractility that does not depend on IP3 signaling.
Sujet(s)
Mélatonine , Vasoconstriction , Amyloid precursor protein secretases/métabolisme , Amyloid precursor protein secretases/pharmacologie , Animaux , Calcium/métabolisme , Protéines contractiles/métabolisme , Protéines contractiles/pharmacologie , Inositol/métabolisme , Inositol/pharmacologie , Mélatonine/pharmacologie , Souris , Souris de lignée C57BL , Contraction musculaire , Muscles lisses vasculaires/métabolisme , Myocytes du muscle lisse/métabolisme , Protéines nucléaires , Facteur de réponse au sérum/métabolisme , Facteur de réponse au sérum/pharmacologie , TransactivateursRÉSUMÉ
Real-time monitoring of drug metabolism in vivo is of great significance to drug development and toxicology research. The purpose of this study is to establish a rapid and visual in vivo detection method for the detection of an intermediate metabolite of the gold (I) drug. Gold (I) drugs such as sodium aurothiomalate (AuTM) have anti-inflammatory effects in the treatment of rheumatoid arthritis. Gold(III) ions (Au3+) are the intermediate metabolite of gold medicine, and they are also the leading factor of side effects in the treatment of patients. However, the rapid reduction of Au3+ to Au+ by thiol proteins in organisms limits the in-depth study of metabolism of gold drugs in vivo. Here we describe a luminescence Au3+ probe (RA) based on ruthenium (II) complex for detecting Au3+ in vitro and in vivo. RA with large Stokes shift, good water solubility and biocompatibility was successfully applied to detect Au3+ in living cells and vivo by luminescence imaging, and to trap the fluctuation of Au3+ level produced by gold (I) medicine. More importantly, the luminescent probe was used to the detection of the intermediate metabolites of gold (I) drugs for the first time. Overall, this work offers a new detection tool/method for a deeper study of gold (I) drugs metabolite.
Sujet(s)
Colorants fluorescents/composition chimique , Aurothiomalate de sodium/composition chimique , Aurothiomalate de sodium/métabolisme , Or/composition chimique , Composés du ruthénium/composition chimique , Animaux , Survie cellulaire/effets des médicaments et des substances chimiques , Cellules HepG2 , Humains , Lipopolysaccharides/toxicité , Souris , Structure moléculaire , Cellules RAW 264.7 , Analyse sur cellule unique , Danio zébréRÉSUMÉ
Chronic infection is considered a risk factor for atherosclerosis. The link between infectious agents and atherosclerosis is manifested by the presence of infection-induced pyroptotic cells in atherosclerotic lesions. Pyroptosis is an inflammatory form of programmed cell death that occurs most frequently upon infection. However, inflammation is not the only cause by which pyroptosis involved in atherosclerosis. During pyroptosis, a large amount of microparticles are released from pyroptotic cells, which not only transfer inflammatory mediators to arterial vessel, but also mediate the interaction between a variety of cells, leading to endothelial injury, macrophage infiltration, vascular smooth muscle cell migration and proliferation, thereby accelerating atherosclerosis. Thus, we proposed hypothesis that pyroptotic cell-derived microparticle is an atherogenic factor in infectious diseases.
Sujet(s)
Athérosclérose , Microparticules membranaires , Maladies transmissibles , Maladies transmissibles/complications , Humains , Macrophages , PyroptoseRÉSUMÉ
INTRODUCTION: Homeostasis of cholesterol is crucial for cellular function, and dysregulated cholesterol biosynthesis is a metabolic event that can lead to hepatic and cardiovascular abnormalities. OBJECTIVE: The aim of this study was to investigate the effects and mechanisms of domain-associated protein (Daxx) and androgen receptor (AR) on intracellular cholesterol synthesis. METHODS: HepG2 cells were transfected with pCDNA3.1(+)/Daxx plasmid or treated with testosterone propionate to observe the effects of Daxx and AR on intracellular cholesterol levels. Co-immunoprecipitation experiments were performed to identify the interaction between Daxx and AR and to explore the regulatory effects of this interaction on cholesterol synthesis. RESULTS: Our experiments showed that AR promoted cholesterol synthesis and accumulation by activating sterol-regulatory element-binding protein isoform 2. AR-induced cholesterol synthesis was inhibited by Daxx; however, the expression of AR was not affected. Further studies demonstrated the existence of direct binding between Daxx and AR and this interaction was required to suppress AR activity. CONCLUSIONS: The Daxx-mediated antagonism of AR depicts a more complete picture as to how Daxx regulates intracellular cholesterol level and provides a new target for treatment of atherosclerosis.
Sujet(s)
Cholestérol/biosynthèse , Protéines corépressives/métabolisme , Chaperons moléculaires/métabolisme , Récepteurs aux androgènes/métabolisme , Composés azoïques , Cholestérol/analyse , Chromatographie en phase liquide à haute performance , Colorimétrie , Cellules HepG2 , Humains , Hydroxymethylglutaryl-CoA reductases/métabolisme , Immunoprécipitation , Protéine-2 de liaison à l'élément de régulation des stérols/métabolismeRÉSUMÉ
A three-dimensional (3-D) residual stress detection technique is proposed to detect and evaluate the residual stress occurring in optical components due to repairs carried out at laser induced damage sites. It is possible with a cross-orthogonal reflective photo-elastic setup to obtain complete 3-D information of the residual shearing stress around the damage site. The damaged volume of the optical component is numerically sliced into multilayers for this purpose and reflected light intensity is recorded from each layer. The shearing stress from the reflected light intensity is then calculated based on photo-elasticity theory. The validity of the approach is also verified in experiments where it could measure 3-D residual stress with an axial resolution of 10 µm along the light path.
RÉSUMÉ
The incidence of gastric cancer is high, especially in China. The present study aims to provide a novel therapeutic target for gastric cancer. Peripheral blood, cancerous and paracancerous tissues were collected from patients with gastric cancer. T-cell immunoglobulin mucin domain-3 (Tim-3) expression in T-cells was measured and the correlation between Tim-3 expression and the T staging of gastric cancer was analyzed. The levels of T-cell secreted interferon (IFN)-γ and tumor necrosis factor (TNF)-α were assessed following Tim-3 signaling pathway activation. A nude mouse model of gastric cancer was established and Tim-3-stimulated T-cells were injected into the mice to evaluate tumor growth. The results of the present study demonstrated that Tim-3 expression levels from the paracancerous and cancerous gastric tissues were significantly increased compared with the peripheral blood, while its expression was significantly increased in cancerous compared with paracancerous gastric tissues. With the T staging of gastric cancer increasing, the expression of Tim-3 gradually increased. The activation of the Tim-3 signaling pathway in T-cells may inhibit IFN-γ and TNF-α secretion, and the results from the nude mice tumor model demonstrated that the inhibitory effect on tumor growth by T-cells was reduced by Tim-3 signaling pathway activation. The expression level of Tim-3 on the surface of tumor infiltrating T-cells in gastric cancer tissue increases significantly and the increased Tim-3 signaling may inhibit the function of T-cells. The results suggest that the increased expression of Tim-3 on T-cells may be involved the development of gastric cancer.
RÉSUMÉ
In recent years, grating based bio-sensors have received much attention due to their promising applications in integrated sensing devices. However, production of high quality, large scale and low cost metal gratings is still challenging. Here, we introduce an extremely simple and low cost method to fabricate metal gratings by peeling off the metal layer from a DVD-R disc. An atomic force microscope image shows that the metal layer is a high quality grating, the period and depth of which are 740 nm and 86 nm, respectively. Based on the fabricated metal grating, refractive index sensing is experimentally achieved using two configurations, where either the resonant wavelength or the modulated laser power is measured. The sensitivity of the sensor by wavelength modulation reaches as high as 637 nmRIU-1, which is comparable with or even higher than that of the existing grating coupled sensors. Our method largely reduces the cost to fabricate high quality metal gratings and will promote the development of grating based SPR sensors.
RÉSUMÉ
A variety of cardiovascular diseases is accompanied by the loss of vascular contractility. This study sought to investigate the effects of curcumin, a natural polyphenolic compound present in turmeric, on mouse vascular contractility and the underlying mechanisms. After mice were administered curcumin (100 mg·kg-1·d-1, ig) for 6 weeks, the contractile responses of the thoracic aorta to KCl and phenylephrine were significantly enhanced compared with the control group. Furthermore, the contractility of vascular smooth muscle (SM) was significantly enhanced after incubation in curcumin (25 µmol/L) for 4 days, which was accompanied by upregulated expression of SM marker contractile proteins SM22α and SM α-actin. In cultured vascular smooth muscle cells (VSMCs), curcumin (10, 25, 50 µmol/L) significantly increased the expression of myocardin, a "master regulator" of SM gene expression. Curcumin treatment also significantly increased the levels of caveolin-1 in VSMCs. We found that as a result of the upregulation of caveolin-1, curcumin blocked the activation of notch1 and thereby abolished Notch1-inhibited myocardin expression. Knockdown of caveolin-1 or activation of Notch1 signaling with Jagged1 (2 µg/mL) diminished these effects of curcumin in VSMCs. These findings suggest that curcumin induces the expression of myocardin in mouse smooth muscle cells via a variety of mechanisms, including caveolin-1-mediated inhibition of notch1 activation and Notch1-mediated repression of myocardin expression. This may represent a novel pathway, through which curcumin protects blood vessels via the beneficial regulation of SM contractility.
Sujet(s)
Curcumine/pharmacologie , Muscles lisses vasculaires/effets des médicaments et des substances chimiques , Myocytes du muscle lisse/effets des médicaments et des substances chimiques , Protéines nucléaires/génétique , Transactivateurs/génétique , Actines/métabolisme , Animaux , Anti-inflammatoires non stéroïdiens/administration et posologie , Anti-inflammatoires non stéroïdiens/pharmacologie , Aorte thoracique/effets des médicaments et des substances chimiques , Aorte thoracique/métabolisme , Cavéoline-1/génétique , Cavéoline-1/métabolisme , Cellules cultivées , Curcumine/administration et posologie , Relation dose-effet des médicaments , Techniques de knock-down de gènes , Humains , Mâle , Souris , Souris de lignée C57BL , Contraction musculaire/effets des médicaments et des substances chimiques , Muscles lisses vasculaires/cytologie , Myocytes du muscle lisse/métabolisme , Récepteur Notch1/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Régulation positive/effets des médicaments et des substances chimiquesRÉSUMÉ
Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626-740 clearly reduced intracellular cholesterol levels and inhibited the expression of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626-740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR-mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells.
Sujet(s)
Protéines adaptatrices de la transduction du signal/métabolisme , Cholestérol/biosynthèse , Protéines nucléaires/métabolisme , Protéines adaptatrices de la transduction du signal/composition chimique , Protéines adaptatrices de la transduction du signal/génétique , Protéines corépressives , Cellules HepG2 , Humains , Protéines et peptides de signalisation intracellulaire/génétique , Protéines et peptides de signalisation intracellulaire/métabolisme , Protéines membranaires/génétique , Protéines membranaires/métabolisme , Chaperons moléculaires , Protéines nucléaires/composition chimique , Protéines nucléaires/génétique , Domaines protéiques , Récepteurs aux androgènes/métabolisme , Protéine-2 de liaison à l'élément de régulation des stérols/génétique , Protéine-2 de liaison à l'élément de régulation des stérols/métabolismeRÉSUMÉ
OBJECTIVE: To explore the influence of cefodizime on CD4/CD8 and T helper 1(Th1)/Th2 cell ratios in peripheral blood of the senile patients with bacterial pneumonia. METHODS: Sixty-three senile patients with bacterial pneumonia were enrolled and divided into two groups randomly. Patients in the control group (n=31) were given intravenous infusion of ceftriaxone sodium, and patients in the observation group (n=32) were given intravenous infusion of cefodizime. The fasting venous blood was taken before and after treatment to detect CD4/CD8 and Th1/Th2 cell ratios with flow cytometry. At the same time, the serum interleukin-2 (IL-2), interferon γ (IFN-γ), IL-4 and IL-10 contents were also detected with ELISA. RESULTS: Before treatment, there was no significant difference in the above indexes between the two groups. After treatment, CD4⺠cells and Th1 cells of the observation group increased while Th2 cells decreased; as a result, the CD4/CD8 and Th1/Th2 cell ratios of the observation group were significantly higher than those of the control group. At the same time, serum IL-2 and IFN-γ contents of the observation group were significantly higher than those of the control group, while serum IL-4 and IL-10 contents were significantly lower than those of the control group. CONCLUSION: Cefodizime can improve the cellular immune function and rectify CD4/CD8 and Th1/Th2 imbalance in peripheral blood of the senile patients with bacterial pneumonia.
Sujet(s)
Antibactériens/administration et posologie , Lymphocytes T CD4+/cytologie , Lymphocytes T CD8+/cytologie , Céfotaxime/analogues et dérivés , Pneumopathie bactérienne/sang , Pneumopathie bactérienne/traitement médicamenteux , Lymphocytes auxiliaires Th1/cytologie , Lymphocytes auxiliaires Th2/cytologie , Sujet âgé , Sujet âgé de 80 ans ou plus , Hémogramme , Céfotaxime/administration et posologie , Femelle , Cytométrie en flux , Humains , Interféron gamma/sang , Interleukine-10/sang , Interleukine-2/sang , Interleukine-4/sang , Mâle , Adulte d'âge moyenRÉSUMÉ
Traffic congestion at bus bays has decreased the service efficiency of public transit seriously in China, so it is crucial to systematically study its theory and methods. However, the existing studies lack theoretical model on computing efficiency. Therefore, the calculation models of bus delay at bays are studied. Firstly, the process that buses are delayed at bays is analyzed, and it was found that the delay can be divided into entering delay and exiting delay. Secondly, the queueing models of bus bays are formed, and the equilibrium distribution functions are proposed by applying the embedded Markov chain to the traditional model of queuing theory in the steady state; then the calculation models of entering delay are derived at bays. Thirdly, the exiting delay is studied by using the queueing theory and the gap acceptance theory. Finally, the proposed models are validated using field-measured data, and then the influencing factors are discussed. With these models the delay is easily assessed knowing the characteristics of the dwell time distribution and traffic volume at the curb lane in different locations and different periods. It can provide basis for the efficiency evaluation of bus bays.