The role of nuclear receptor transcription factor NR2F6 in tumor / 生物工程学报

Nuclear receptor subfamily 2, group F, member 6 (NR2F6) is a member of orphan nuclear receptors, which is expressed in major tissues and organs of the human body, and plays an important role in the regulation of various biological functions and gene expressions. Recent studies have shown that the expression of NR2F6 was up-regulated in a variety of malignant tumors and showed significant correlations with cancer progression. These findings triggered the widespread interest in understanding the relationship between NR2F6 and cancer development and progression. In addition, the latest studies have underscored that NR2F6 was involved in enhancing antitumor immune responses that could serve as a potential target for immune regulation. This review summarizes the biological functions of NR2F6 and its role in tumors, with the aim to provide new insights into effective cancer therapies.

Effects of bile acids and their related nuclear receptors on intestinal mucosal barrier / 中华肝胆外科杂志

Bile acids are the end product of cholesterol metabolism,which is the main component of bile.Bile acids can not only promote the absorption of fat and fat-soluble vitamins but also be used as the important signal molecules to activate nuclear receptors.It regulates metabolism of bile acids and intestinal homeostasis.The bile acids' effect on intestinal mucosal barrier function has been controversial until now.Bile acids is both hydrophilic and hydrophobic simultaneously.Hydrophilic bile acid can promote cell proliferation,while hydrophobic bile acid can promote cell apoptosis.The stronger the hydrophobicity is,the greater the cellular damage effect will be.The activation of nuclear receptor by bile acids can protect intestinal mucosal barrier.New research progress of the bile acid regulation in intestinal mucosal barrier function is reviewed in this article.

Application of nuclear receptor in pathogenesis research and drug development for nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease in developed countries, and in recent years, the prevalence rate of NAFLD tends to increase in China, which brings heavy burden to the social health system. The development and progression of NAFLD are affected by the interaction between multiple influencing factors including genetic and epigenetic factors, transcription factors, hormones, nutrition, and environmental factors. This article reviews the research advances in the role of nuclear receptor in the pathogenesis of NAFLD, in order to deepen the understanding of this disease.

Current trends in drug metabolism and pharmacokinetics

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.

Effects of scoparone on the expression of RORγt and related factors in experimental allergic rhinitis rats / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the effects of behavior, pathology, the serum IL-17, IL-23 level, and the expressing of RORγt, IL-17 and IL-23 mRNA in nasal tissues of experimental allergic rhinitis rats after the scoparone treatment. METHODS The animal model were divided into 4 groups: normal control group(group NC), allergic rhinitis group(group AR), artemolactone group(group Sco) and dexamethasone group(group Dxm). The symptom score, HE staining of the nasal mucosa, IL-17 and IL-23 level in serum measured by ELISA, the RORγt, IL-17 and IL-23 mRNA level detected by RTPCR. RESULTS Symptoms and inflammatory pathology were relieved in the experimental group after scoparone treatment. The serum levels of the IL-17, IL-23 in group Sco and group Dxm were little higher than that in group NC. The levels of RORγt, IL-17 and IL-23 mRNA in group AR were significantly higher than that in the other three groups. The levels of RORγt, IL-17 and IL-23 mRNA in group Sco and group Dxm were little higher than that in the group NC. CONCLUSION Sco could significantly inhibited or eliminated the allergy symptoms of AR in rats, and could reduce the severity and inflammatory response of diseases.

Renal protective effect of Ganoderma lucidum / 中国药理学与毒理学杂志

OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho-logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel-lular carcinoma.The purpose of this study was to determine whether Ganoderma lucidum polysaccha-ride peptide (GLPP) has therapeutic effect on NAFLD. METHODS ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic path-ways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting. Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. RESULTS GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepato-cytes induced by oleic acid and palmitic acid. CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a therapeutic drug for NAFLD.

The Protective effect of oleanolic acid on acute cholestatic liver injury in rats / 中华急诊医学杂志

Objective The protective effect of oleanolic acid on acute cholestatic liver injury in rats. Methods Thirty male SD rats were randomly divided into 3 groups ( n= 10 per group): sham group, bile duct ligated (BDL) group, and bile duct ligated with oleanolic acid (BDL+OA ) group. After 7 days, liver samples in all rats were collected. Expressions of bile acids pump and nuclear receptors at mRNA and protein levels were detected by RT- qPCR and Western blotting. Results At mRNA level, the expression of Mrp4 and Oatp1 expression in the BDL and BDL+OA groups were increased as compared with that in the sham group. The expression of Mrp4 increased 1.8 times in the BDL group and increased 2.3 times in the BDL+OA group (P<0.05), but the expression of Oatp1 was not statistically significant; AhR was increased 1.7-fold in the BDL group and 2.8 times in the BDL+OA group, Nrf2 was increased 1.5-fold in the BDL group and 2.1 times in the BDL+OA group with statistically significant difference. At the protein level, in the BDL group, Mrp4 expression increased 1.3 times, Oatp1 expression increased 1.5 times, AhR expression increased 1.3 times, Nrf2 expression increased 1.4 fold; in the BDL+OA group, Mrp4 expression increased 1.8 fold, AhR expression increased 1.9 fold, with statistical significance between the two groups. Oatp1 expression increased 1.4-fold in the BDL+OA group as compared with the BDL group showing no statistical significance. Conclusions Oleanolic acid stimulates the hepatic expression of bile acids pump Mrp4 associated with the activation of nuclear receptors AhR and Nrf2 in acute bile ductligated rats.

Association of NR1I2 gene polymorphisms and time of progression to AIDS

BACKGROUND The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS. OBJECTIVE To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients. METHODS Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis. FINDINGS Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms. MAIN CONCLUSIONS Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression.

Chronopharmacokinetics of gefitinib and its mechanisms in tumor-bearing nude mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of the dosing time on the pharmacokinetics of gefitinib and its potential mechanism. METHODS Female BALB/c nude mice were housed under standardized 12 h light/dark circadian conditions(light on at 7:00,off at 19:00)for two weeks before a non-small cell lung cancer(NSCLC)model was established. Two weeks later,they were divided into 2 groups(8:00,20:00)randomly. Gefitinib was orally administered at the dose of 1 mg · kg-1 to the mice in each group at 8:00 or 20:00,respectively. Blood was collected at 10 different time points after each administration. Livers were collected every 4 h during the 24 h period from the non-administrated nude mice of NSCLC model. The plasma concentration of gefitinib was determined through an HPLC-MS/MS and the parameters were calculated by WinNonlin 6.3. The total RNA was extracted from livers,purified, synthesized to cDNA that was subjected to qRT-PCR analysis for mRNA expression levels of cyto?chrome P450 enzymes(Cyp)3a11,Cyp3a13,pregnane X receptor(PXR)and constitutive androstane receptor (CAR). RESULTS The area under the plasma concentration-time curve (AUC) and mean residence time (MRT) of 8:00 administration group were higher than those of 20:00 administration group(P<0.05). The clearance(Clz/F) of 8:00 administration group was lower than that of 20:00 administration group(P<0.05). The mRNA expression levels of PXR and CAR were consistent with those of Cyp3a11 and Cyp3a13. CONCLUSION Circadian rhythm exists in the pharmacokinetics of gefitinib and it may be closely related to CYP3A and its regulator genes.

Hepatic peroxisome proliferator-activated receptor γ and α-mRNA expression in HCV-infected adults is decreased by HIV co-infection and is also affected by ethnicity

OBJECTIVE: To determine peroxisome proliferator activated receptor α and γ mRNA expression in liver tissue of hepatitis C virus-infected patients with and without human immunodeficiency virus and its possible contribution to an acceleration of liver disease progression. METHODS: We measured peroxisome proliferator-activated receptor α and γ mRNA expression by real-time polymerase chain reaction in liver tissues from 40 subjects infected only with hepatitis C virus, 36 subjects co-infected with hepatitis C virus and human immunodeficiency virus and 11 normal adults. RESULTS: Hepatic mRNA expression of both peroxisome proliferator-activated receptors was significantly lower in hepatitis C virus-infected subjects with and without human immunodeficiency virus co-infection compared to the controls. Non-black race was also identified as a predictor of lower peroxisome receptor α and γ mRNA expression. Compared to subjects infected only with hepatitis C virus, liver peroxisome receptor γ mRNA expression was significantly lower in hepatitis C virus/human immunodeficiency virus-co-infected subjects (0.0092 in hepatitis C virus/human immunodeficiency virus-co-infection vs. 0.0120 in hepatitis C virus-only; p=0.004). Hepatic peroxisome receptor α mRNA expression in the hepatitis C virus-infected patients was lower in the presence of human immunodeficiency virus co-infection in non-black subjects (0.0769 vs. 0.1061; p=0.02), whereas the levels did not vary based on human immunodeficiency virus status among black subjects. CONCLUSION: mRNA expression of both peroxisome proliferator-activated receptors is impaired in hepatitis C virus-infected liver and further reduced by human immunodeficiency virus co-infection, although the suppressive effects of the viruses are substantially mitigated in black patients.

Lung Retinoid Metabolism and Signaling in Chronic Obstructive Pulmonary Disease.

There are a number of sites that are required for the production and/or action of all-trans retinoic acid (ATRA). In particular, interruption of different components of the chain of trafficking and metabolism has been associated with cancers arising in numerous organs of the body. Preliminary work suggests that such interruptions may be a factor in lung disorders induced by the smoke exposure. The active metabolite of retinoid, ATRA offers a therapeutic strategy to protect against functional abnormality in the lung, including chronic obstructive pulmonary disease (COPD). This review deals with the lung retinoid metabolism and mediators of retinoid trafficking and signaling with special emphasis on their roles in health and disease.

Melatonin inhibits adipogenic differentiation of bone marrow mesenchymal stem cells through retinoid-related orphan receptor alpha / 中国组织工程研究

BACKGROUND:Our previous studies have demonstrated that melatonin inhibits the adipogenic differentiation of bone marrow mesenchymal stem cels. However, the mechanism underlying the effect of melatonin on adipogenesis is stil unknown. OBJECTIVE:To determine whether melatonin can inhibit the adipogenesis of bone marrow mesenchymal stem cels through retinoid-related orphan receptor α. METHODS:Bone marrow mesenchymal stem cels were isolated and purified by density gradient centrifugation combined with cellattachment culture. The phenotype was investigated by flow cytometry. Then, cels were induced for adipogenic differentiation with melatonin, CGP52608 and normal adipose tissue, respectively. The levels of retinoid-related orphan receptor α mRNA and protein were investigated by real-time RT-PCR and western blot assay, respectively. Further, the effect of retinoid-related orphan receptor α on the dipogenic differentiation of bone marrow mesenchymal stem cels was investigated by CGP52608. RESULTS AND CONCLUSION:The primary isolated bone marrow mesenchymal stem cels were spindle-shaped fibroblast-like cels. These cels did not express hematopoietic stem cels markers: CD34 and CD45; and highly expressed MSC markers: CD29, CD44, and CD10. The result of RT-PCR demonstrated that melatonin nuclear receptor, retinoid-related orphan receptor α, was highly expressed in bone marrow mesenchymal stem cels and the expression of retinoid-related orphan receptor α was further enhanced by melatonin in a dose-dependent manner, which was confirmed at protein level by western blot assay. During adiogenesis, the expression of retinoid-related orphan receptor αmRNA was up-regulated in the early stage, but maintained at a low level in the mild-later stage. While the retinoid-related orphan receptor α was activated by agonist CGP52608, the adipogenic differentiation of bone marrow mesenchymal stem cels was inhibited, which was similar to the inhibitory effect of melatonin. Therefore, melatonin inhibited the adipogenic differentiation of bone marrow mesenchymal stem cels through retinoid-related orphan receptor α, suggesting that melatonin plays an important role in the differentiation of adipocytes.

Influence of PPARA, RXRA, NR1I2 and NR1I3 gene polymorphisms on the lipid-lowering efficacy and safety of statin therapy / Influência de polimorfismos nos genes PPARA, RXRA, NR1I2 e NR1I3 na eficácia hipolipemiante e na segurança da terapia com estatinas

OBJECTIVE: The aim of the present study was investigate the association between six genetic variants in the nuclear receptor genes PPARA, RXRA, NR1I2 and NR1I3 and the lipid-lowering efficacy and safety of statin therapy. SUBJECTS AND METHODS: The study was carried out on 240 Brazilian hypercholesterolemic patients on simvastatin and atorvastatin therapy. The polymorphisms were analyzed by PCR-based methods. RESULTS: The NR1I3 rs2307424 genotype distribution was different between subjects with and without adverse drug reactions. Among subjects in the ADR group, no T/T homozygotes were observed for this polymorphism, while in the non-ADR group the frequency of this genotype was 19.4% (P = 0.007, after multiple testing corrections P = 0.042). CONCLUSION: The polymorphisms investigated in PPARA (rs1800206), RXRA (rs11381416), and NR1I2 (rs1523130) did not influence the lipid-lowering efficacy and safety of statin. Our results show the possible influence of NR1I3 genetic variant on the safety of statin.

OBJETIVO: O objetivo deste estudo foi investigar a associação de seis variantes genéticas nos genes de receptores nucleares PPARA, RXRA, NR1I2 e NR1I3 na eficácia hipolipemiante e na segurança da terapia com estatinas. SUJEITOS E MÉTODOS: O estudo foi realizado com 240 pacientes hipercolesterolêmicos em terapia com sinvastina e atorvastatina. Os polimorfismos foram analisados por meio de métodos baseados em PCR. RESULTADOS: A distribuição da frequência genotípica do polimorfismo NR1I3 rs2307424 foi diferente entre os pacientes com e sem efeito adverso à medicação; entre os sujeitos do grupo com efeitos adversos, nenhum homozigoto T/T foi observado, enquanto no grupo de indivíduos sem efeitos adversos a frequência desse genótipo foi 19,4% (P = 0,007, após correção para múltiplos testes P = 0,042). CONCLUSÃO: Os polimorfismos investigados nos genes PPARA (rs1800206), RXRA (rs11381416) e NR1I2 (rs1523130) não foram associados com eficácia hipolipemiante e segurança da terapia com estatinas. Nossos resultados mostram uma possível influência de variantes do gene NR1I3 (rs2307424) no desenvolvimento de efeitos adversos à terapia com estatinas.

Crosstalk between RXR, LXR and VDR within blood mononuclear cellular model.

An accumulation of data from in vitro to in vivo model system has established a pivotal role of three crucial ligand activated nuclear receptors RXR, LXR-α and VDR for their ability to regulate an array of genes involved in regulation of fundamental cellular processes to patho-physiological situations. Keeping in view RXR as a common heterodimeric partner for LXR-α and VDR, the present study was designed to dissect the interrelationship between these three nuclear receptors in peripheral blood mononuclear cellular model. The present study revealed that all the three nuclear receptors displayed auto regulation in response to their specific ligands; Both LXR-α and VDR regulated the expression of their heterodimeric partner RXR; and VDR was regulated by LXR-α through its ability to modulate SREBP response element present in the promoter region of VDR gene. Based on these findings, the role of these nuclear receptors could be better understood in various nuclear receptor mediated pathological processes.

Role of nuclear receptors in the regulation of lipid metabolism / 国际外科学杂志

Nuclear receptors,the superfamily of ligand-activated transcription factors,play crucial role in the regulation of gene expression of the lipid metabolism,and are involved in many metabolic diseases,such as cholesterol gallstone disease.Recently many domestic and foreign researches on the role of nuclear receptors in the lipid metabolism,help to further elucidate the biomolecular pathogenesis of cholesterol gallstone disease and other diseases associated with the lipid metabolism.

Síndrome de resistência ao hormônio tireoidiano e dominância negativa: revisão de literatura / Thyroid resistance hormone syndrome and negative dominance: a review of literature

A síndrome de resistência ao hormônio tireoidiano é doença genética, caracterizada pela resposta reduzida dos tecidos-alvo ao hormônio tireoidiano. É autossômica dominante, causada, na maioria das vezes, por mutações na isoforma beta do receptor de hormônio tireoidiano (TR?). Os pacientes com a síndrome apresentam níveis séricos elevados de tiroxina livre (T4) e tri-iodotironina livre (T3) associados a feedback negativo anormal na regulação do hormônio estimulador da tireoide (TSH) e do hormônio liberador de TSH (TRH). Por essa razão, os níveis do hormônioestimulador estão pouco aumentados ou inapropriadamente normais. O diagnóstico final é feito pelo sequenciamento do gene da isoforma beta do receptor de hormônio tireoidiano. Os indivíduos afetados são, na maioriadas vezes, heterozigotos com mutações no gene TR?. Na fisiopatogenia da doença, tem sido descrito que o gene mutado inibe a função do gene normal, em um fenômeno conhecido como dominância negativa que, por sua vez, ocorre nos genes regulados negativamente e positivamente pelo hormônio tireoidiano. O mecanismo molecular da dominância negativa envolve: (1) competição da ligação do receptor mutante ao DNA, (2) dimerização do receptor mutante com o receptor do retinoide X ou com o receptor normal e (3) interação do receptor mutado com correguladores,o que acarreta em falha da regulação transcricional pelo hormônio tireoidiano. A intensidade da síndrome de resistência ao hormônio tireoidiano depende, então, em parte, do nível de expressão do receptor mutado e do tipo de mutação.

Thyroid resistance hormone syndrome is a genetic disease characterized by a reduced responsiveness of target tissues to thyroid hormone. Such patients show persistent elevation of circulating free thyroxine (T4) and free triiodothyronine (T3) levels associated with nonsuppressed serum thyrotropin (TSH). Inheritance is autosomal dominant and mutations inthe TR? gene have been identified in the majority patients with the syndrome. Most patients are heterozygous, with only one mutated TR? gene. In the pathogenesis of the disease, it has been described that the TR? mutant impairs the normal function of TR wild type (TRwt), a phenomenon described as a dominant-negative effect, which occurs in positive and negative TH regulated genes. The mutant receptor diminishes TRwt function by competing with normal receptor for DNA binding, by dimerizing with retinoid X receptor or normal receptor, and also by interacting with coregulators and disrupting the transcription activity modulated by thyroid hormone.

Effects of a methanolic fraction of soybean seeds on the transcriptional activity of peroxisome proliferator-activated receptors (PPAR)

Since the anti-inflammatory, antidiabetic and hypolipidemic effects of soy isoflavones may be mediated by activation of peroxisome proliferator-activated receptors (PPAR), the present study investigated whether the methanolic fractions obtained from soybean seeds (E1) and soybean seed coats with hypocotyls (E2) could influence PPARα, PPARγ and PPARβ/δ transcriptional activity. The isoflavones from E1 and E2 were quantified by HPLC analysis. E1 and E2 were rich in isoflavones (daidzin, glycitin, genistin, malonyldaidzin, malonylglycitin, malonylgenistin, daidzein, glycitein, and genistein). Moreover, E1 and E2 showed no evidence of genetically modified material containing the gene CP4 EPSPS. To investigate PPAR transcriptional activity, human promonocytic U-937 cells were treated with E1 and E2 (200, 400, 800, and 1600 µg/mL), positive controls or vehicle. Data are reported as fold-activation of the luciferase reporter driven by the PPAR-responsive element. Dose-response analysis revealed that E1 and E2 induced the transcriptional activity of PPARα (P < 0.001), with activation comparable to that obtained with 0.1 mM bezafibrate (positive control) at 1600 µg/mL (4-fold) and 800 µg/mL (9-fold), respectively. In addition, dose-response analysis revealed that E1 and E2 activated PPARβ/δ (P < 0.05), and the activation at 800 µg/mL (4- and 9-fold, respectively) was comparable to that of 0.1 mM bezafibrate (positive control). However, no effect on PPARγ was observed. Activation of PPARα is consistent with the lipid-lowering activity of soy isoflavones in vivo, but further studies are needed to determine the physiological significance of PPARβ/δ activation.

Receptores nucleares y metabolismo de lípidos: implicaciones cardiovasculares / Nuclear receptors and lipid metabolism: cardiovascular implications

La superfamilia de receptores de hormonas nucleares, es un amplio grupo de proteínas cuya función es actuar como factores de transcripción para modular, de manera positiva o negativa, la expresión de genes involucrados en procesos de diferenciación, crecimiento, reproducción y metabolismo. Dada su participación en procesos fisiológicos claves, las disfunciones asociadas con estos receptores tienen enormes implicaciones en enfermedades de elevada importancia en salud pública como la enfermedad cardiovascular, la diabetes mellitus tipo 2 y el cáncer, entre otras. En este trabajo se revisan algunos aspectos de esta superfamilia de proteínas, incluyendo su estructura, relación con el metabolismo de lípidos e implicaciones cardiovasculares. El trabajo se enfoca en los receptores activados por el proliferador del peroxisoma (PPAR), aunque se da una breve mirada a los receptores X hepáticos (LXR).

Nuclear hormone receptors superfamily are a wide group of proteins which function is to act as transcription factors in order to modulate in a positive or negative way the expression of genes involved in differentiation processes, growth, reproduction and metabolism. Given its participation in key pathologic processes, the disfunctions associated to these receptors have huge implications in diseases of great importance in public health such as cardiovascular disease, diabetes mellitus type 2, and cancer between others. Some aspects of this protein superfamily are reviewed in this study, including its structure, relationship with lipid metabolism and cardiovascular implications. This study focuses on the peroxisome proliferator-activated receptor (PPAR), and briefly on the liver X receptors (LXR).

Changes of nuclear receptors-glucocorticoid receptors in locus ceruleus neurons of posttraumatic stress disorder-like rat / 解剖学报

Objective To investigate expression changes of nuclear receptors-glucocorticoid receptors (GR) in the locus ceruleus neurons of posttraumatic stress disorder(PTSD)like rats. Methods Sixty adult healthy male Wistar rats were enrolled in the experiment. PTSD-like rat model was established by single prolonged stress (SPS). There was no SPS stimulation in the control group and the rats of the other five groups were undisturbedly raised for 24 hours, 4 days,7 days,14 days and 28 days respectively after SPS stimulation.The expressions of glucocorticoid receptors in the locus ceruleus nucleus of all groups were detected with Nissl staining, immunohistochemistry,Western blotting and PCR, and image analysis and statistical analysis were performed. Results GR was distributed in the nucleus of coeruleus neurons, GR expression was showed after 24 hours, 4 days, 7 days treatment and gradually increased, restorative downregulation was seen after 14 days and 28 days, but still high(P<0.05). Conclusion After SPS, the GR locus ceruleus temporarily increased and then lowered, suggesting that PTSD rat locus coeruleus neurons in nuclear receptor-GR expression changes may directly involve in the continuing spirit of PTSD symptoms occurred in the development process.

Effect of Extract of Carapax et Plastrum Testudinis on Nuclear Receptor in the Proliferation of Rat Mesenchymal Stem Cell in Vitro / 广州中医药大学学报

[Objective] To observe the effect of extract of Carapax et Plastrum Testudinis (ECPT) on nuclear receptor in the proliferation of rat mesenchymal stem cell (MSC) in vitro. [Methods] The rat MSC dissociated from bone marrow by density gradient method were cultured and identified by marking of bromodeoxyuridine (Brdu) and staining of CD44. Then different doses of ECPT (3333, 333.3 and 33.33 ?g/mL) were respectively added into in-vitro cultured MSC for 12, 24, 72 and 120 hours. The expression of retinoic acid receptor-?(RAR?), vitamin D receptor (VDR), estrogen receptor (ER), glucocorticoid receptor (GR), thyroid hormone receptor-?(TR?) and peroxisome proliferator-activated receptor ?(PPAR?) in MSC was detected by immunohistochemistry and immunofluorescence methods. [Results] The number of RAR?-and VDR-positive cells in ECPT groups was higher than that in the control group (P