RESUMO
Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.
Assuntos
Criptococose , Cryptococcus neoformans , Meningoencefalite , T-Linfocitopenia Idiopática CD4-Positiva , Masculino , Humanos , Pessoa de Meia-Idade , Próstata , Criptococose/complicações , Criptococose/diagnóstico , T-Linfocitopenia Idiopática CD4-Positiva/complicações , T-Linfocitopenia Idiopática CD4-Positiva/diagnósticoRESUMO
Resistance to telithromycin and off-target effects associated with the metabolic instability present serious and challenging problems for the development of novel macrolides. Herein, studies of hybrids of macrolides and quinolones (termed macrolones) bridged with linkers from 11,12-cyclic carbamate of macrolides revealed different structure-activity relationships from the previously reported macrolones bridged with linkers derived from 6-, 9- and 4''-positions of macrolides. The optimized macrolone 34 g with a longer and rigid sidechain than telithromycin had improved metabolic stability compared to telithromycin (t1/2: 110 vs 32 min), whose future has been heavily clouded by metabolic issues. Moreover, 34 g was 38-fold more potent than telithromycin against A2058/2059-mutated Mycoplasma pneumoniae (8 vs 315 µM), which may be attributed to a novel mode of action between the carboxylic acid of quinolone moiety and the bacterial ribosome. This work increases the prospect for discovery of novel and safe antibacterial agents to combat serious human infectious diseases.
Assuntos
Cetolídeos , Quinolonas , Antibacterianos/farmacologia , Humanos , Cetolídeos/farmacologia , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Mycoplasma pneumoniae , Quinolonas/farmacologia , Relação Estrutura-AtividadeRESUMO
The rat everted intestinal sac model was adopted to investigate the absorption of total flavonoids from Coreopsis tinctoria in different intestinal segments. Cyaniding-3-O-ß-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-ß-D-glucoside, iso-okanin, marein and 3,5-dicaffeoylquinic acid which as the major chemical components of total flavonoids from C. tinctoria were selec-ted as the study objects to evaluate the absorption characteristics of each component in different intestinal segments. The results showed that the absorption of seven components of total flavonoids at different intestinal segments was in consistent with zero order absorption rate. The K_a of chlorogenic acid, flavanomarein, quercetagetin-7-O-ß-D-glucoside, isookanin and 3,5-dicaffeoylquinic acid increased with increasing of concentration of total flavonoids(P<0.05), indicating that the intestinal absorption of these five components was passive transport. The K_a of cyaniding-3-O-ß-D-glucoside and marein showed a weak concentration dependence, suggesting that the absorption of them may be an positive and passive co-existing mode. The result of absorption in different intestinal segments showed that cyaniding-3-O-ß-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-ß-D-glucoside, marein and 3,5-dicaffeoylquinic acid were mainly absorbed in ileum, while isookanin was mainly absorbed in jejunum. The total flavonoids of C. tinctoria are selectively absorbed in intestinal tract, the rat everted intestinal sac model can be used to evaluate the multi-component intestinal absorption characteristics of total flavonoids from C. tinctoria.
Assuntos
Coreopsis , Animais , Ácido Clorogênico , Flavonoides , Absorção Intestinal , Extratos Vegetais , RatosRESUMO
BACKGROUND: Depression and anxiety among general hospital patients are common and under-recognized in China. This study aimed toward developing a short questionnaire for screening depression and anxiety in non-psychiatric clinical settings, and to test its reliability and validity. METHODS: The item pool which included 35 questions about emotional distress was drafted through a comprehensive literature review. An expert panel review and the first clinical test with 288 general hospital patients were conducted for the primary item selection. The second clinical test was performed to select the final item in 637 non-psychiatric patients. The reliability and validity of the final questionnaire were tested in 763 non-psychiatric patients, in which 211 subjects were interviewed by psychiatrists using Mini International Neuropsychiatric Interview (MINI). Multiple data analysis methods including principal components analysis (PCA), item response theory (IRT), and receiver operating characteristic (ROC) curve were used to select items and validate the final questionnaire. RESULTS: The series selection of items resulted in a 9-item questionnaire, namely Huaxi Emotional-distress Index (HEI). The Cronbach's α coefficient of HEI was 0.90. The PCA results showed a unidimensional construct. The area under the ROC curve (AUC) was 0.88 when compared with MINI interview. Using the optimal cut-off score of HEI (≥11), the sensitivity and specificity were 0.880 and 0.766, respectively. CONCLUSIONS: The HEI is considered as a reliable and valid instrument for screening depression and anxiety, which may have substantial clinical value to detect patients' emotional disturbances especially in the busy non-psychiatric clinical settings in China.
Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Adolescente , Adulto , Povo Asiático/psicologia , Depressão/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
Non-alcoholic fatty liver disease (NAFLD) has reached an epidemic level globally, which is recognized to form non-alcoholic steatohepatitis (NASH) by the "two-hit" model, including oxidative stress and inflammation. AMP-activated protein kinase (AMPK) has long been regarded as a key regulator of energy metabolism, which is recognized as a critical target for NAFLD treatment. Here we introduce a natural product, demethyleneberberine (DMB), which potentially ameliorated NAFLD by activating AMPK pathways. Our study showed that the intraperitoneal injection of DMB (20 or 40 mg/kg body weight) decreased hepatic lipid accumulation in methionine and choline deficient (MCD) high-fat diet feeding mice and db/db mice. The further investigation demonstrated that DMB activated AMPK by increasing its phosphorylation in vitro and in vivo. Accompanied with AMPK activation, the expression of lipogenic genes were significantly reduced while genes responsible for the fatty acid ß-oxidation were restored in DMB-treated NAFLD mice. In addition, the remarkable oxidative damage and inflammation induced by NAFLD were both attenuated by DMB treatment, which is reflected by decreased lipid oxidative product, malonaldehyde (MDA) and inflammatory factors, tumor necrosis factor α (TNFα) and interleukin 1ß (IL-1ß). Based on all above, DMB could serve as a novel AMPK activator for treating NAFLD and preventing the pathologic progression from NAFLD to NASH by inhibiting the oxidative stress and inflammation.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/uso terapêutico , Berberina/análogos & derivados , Ativação Enzimática/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Berberina/uso terapêutico , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
Excessive alcohol consumption induces oxidative stress and lipid accumulation in the liver. Mitochondria have long been recognized as the key target for alcoholic liver disease (ALD). Recently, the artificial mitochondria-targeted antioxidant MitoQ has been used to treat ALD effectively in mice. Here, we introduce the natural mitochondria-targeted antioxidant demethyleneberberine (DMB), which has been found in Chinese herb Cortex Phellodendri chinensis. The protective effect of DMB on ALD was evaluated with HepG2 cells and acutely/chronically ethanol-fed mice, mimicking two common patterns of drinking in human. The results showed that DMB, which is composed of a potential antioxidant structure, could penetrate the membrane of mitochondria and accumulate in mitochondria either in vitro or in vivo. Consequently, the acute drinking-caused oxidative stress and mitochondrial dysfunction were significantly ameliorated by DMB. Moreover, we also found that DMB suppressed CYP2E1, hypoxia inducible factor α, and inducible nitric oxide synthase, which contributed to oxidative stress and restored sirtuin 1/AMP-activated protein kinase/peroxisome proliferator-activated receptor-γ coactivator-1α pathway-associated fatty acid oxidation in chronic ethanol-fed mice, which in turn ameliorated lipid peroxidation and macrosteatosis in the liver. Taking these findings together, DMB could serve as a novel and potential therapy for ALD in human beings.
Assuntos
Antioxidantes/farmacologia , Berberina/análogos & derivados , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antioxidantes/uso terapêutico , Berberina/farmacologia , Berberina/uso terapêutico , Citocromo P-450 CYP2E1/metabolismo , Modelos Animais de Doenças , Etanol/efeitos adversos , Ácidos Graxos/metabolismo , Células Hep G2 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/etiologia , Masculino , Camundongos , Mitocôndrias/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Oxirredução/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Human parechoviruses (HPeVs) are widespread pathogens causing a wide spectrum of diseases. The prevalence and genetic diversity of HPeV in children with acute diarrhea in China is not well known. The purpose of this study was to investigate the epidemiological characteristics of HPeV in Guangzhou, China. A total of 328 stool specimens collected from children under the age of 5 years with acute diarrhea were tested for the presence of HPeV. Of these, 44 (13.4 %, 44/328) were HPeV positive, with the majority of the infected children (97.7 %, 43/44) being younger than two years of age. HPeV was more frequently detected during July and August. The epidemiological profile of co-infections was similar to that observed in a previous study. Six different HPeV genotypes, including HPeV1, -3, -4, -5, -6, and -14, were identified, and of these, HPeV14, a rarely reported genotype, was reported for the first time in children with acute gastroenteritis in China. In summary, this study clearly demonstrated that HPeV circulating in Guangzhou, China, is genetically diverse, including six genotypes, and it provides useful epidemiological data on the features of HPeV infection in this area.
Assuntos
Gastroenterite/virologia , Parechovirus/isolamento & purificação , Infecções por Picornaviridae/virologia , Pré-Escolar , China/epidemiologia , Feminino , Gastroenterite/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Filogenia , Infecções por Picornaviridae/diagnóstico , Infecções por Picornaviridae/epidemiologiaRESUMO
PURPOSE: Investigating risk factors for amputation in patients with diabetic foot ulcer (DFU) and developing a nomogram prediction model. METHODS: We gathered case data of DFU patients from five medical institutions in Anhui Province, China. Following eligibility criteria, a retrospective case-control study was performed on data from 526 patients. RESULTS: Among the 526 patients (mean age: 63.32 ± 12.14), 179 were female, and 347 were male; 264 underwent amputation. Univariate analysis identified several predictors for amputation, including Blood type-B, Ambulation, history of amputation (Hx. Of amputation), Bacterial culture-positive, Wagner grade, peripheral arterial disease (PAD), and laboratory parameters (HbA1c, Hb, CRP, ALB, FIB, PLT, Protein). In the multivariate regression, six variables emerged as independent predictors: Blood type-B (OR = 2.332, 95%CI [1.488-3.657], p < 0.001), Hx. Of amputation (2.298 [1.348-3.917], p = 0.002), Bacterial culture-positive (2.490 [1.618-3.830], p <0.001), Wagner 3 (1.787 [1.049-3.046], p = 0.033), Wagner 4-5 (4.272 [2.444-7.468], p <0.001), PAD (1.554 [1.030-2.345], p = 0.036). We developed a nomogram prediction model utilizing the aforementioned independent risk factors. The model demonstrated a favorable predictive ability for amputation risk, as evidenced by its area under the receiver operating characteristics (ROC) curve of 0.756 and the well-fitted corrected nomogram calibration curve. CONCLUSION: Our findings underscore Blood type-B, Hx. Of amputation, Bacterial culture-positive, Wagner 3-5, and PAD as independent risk factors for amputation in DFU patients. The resultant nomogram exhibits substantial accuracy in predicting amputation occurrence. Timely identification of these risk factors can reduce DFU-related amputation rates.
Assuntos
Amputação Cirúrgica , Pé Diabético , Nomogramas , Humanos , Pé Diabético/cirurgia , Pé Diabético/microbiologia , Pessoa de Meia-Idade , Feminino , Masculino , Estudos Retrospectivos , Amputação Cirúrgica/estatística & dados numéricos , Idoso , Fatores de Risco , Estudos de Casos e Controles , China/epidemiologiaRESUMO
Background: Grade IV circular hemorrhoids are difficult to treat. We aim to describe the modified whitehead hemorrhoidectomy procedure and to assess the effectiveness and safety of this procedure for grade IV circular hemorrhoid patients. Methods: Patients with grade â £ circular hemorrhoids who underwent modified Whitehead hemorrhoidectomy and partial hemorrhoidectomy for fourth-degree circular mixed hemorrhoids were retrospectively reviewed. Clinical data were extracted from the database at our institution, and long-term postoperative complications were assessed through repeated outpatient examinations and telephonic communication. Results: A total of 205 patients were included in this study. The mean operative time was 59.2 ± 13.8 min. The average hospital stay was 4.6 ± 1.0 days. For postoperative complications, 66 (32.2%) patients had urinary retention, 10 (4.9%) patients had a sense of incomplete rectal emptying, 5 (2.4%) patients had anal incontinence, and 6 (2.9%) patients had wound infection. For long-term postoperative complications, 3 (1.5%) patients experienced mild to moderate anal stricture, 2 (1%) patients experienced mucosal ectropion, they all had smooth recoveries, and none of them needed secondary surgery. None of these patients had a hemorrhoid recurrence. A total of 205 patients who received modified Whitehead hemorrhoidectomy and 161 who received partial hemorrhoidectomy were included. There were no residual hemorrhoids in patients who received modified Whitehead hemorrhoidectomy, and none had hemorrhoid recurrence. Fifty-eight patients who received partial hemorrhoidectomy had hemorrhoidal residues, and 19 patients experienced hemorrhoid recurrence. After modified Whitehead hemorrhoidectomy, 3 patients developed anal stenosis, and 2 had mucosal ectropion. Four patients developed anal stricture after partial hemorrhoidectomy, and none had mucosal ectropion. They all had smooth recoveries, and none of them needed a secondary surgery. For the mean duration of surgery, postoperative bleeding, postoperative pain, wound infection, sense of incomplete rectal emptying, anal incontinence, and urinary retention, no statistically significant differences were found between the two groups. Conclusions: Compared with partial hemorrhoidectomy, modified whitehead hemorrhoidectomy is an effective and safe surgical procedure and does not significantly increase the risk of anal stenosis and mucosal ectropion for grade IV circular hemorrhoid patients. Prospective randomized controlled trials are needed to verify our results.
RESUMO
Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.
RESUMO
Zero-valent iron (ZVI) materials have been developed and applied to treat various pollutants due to their strong reducing properties and large specific surface area. Red mud contains a large amount of iron oxide and therefore can be used as a source of iron base for the preparation of ZVI materials. Industrial reduction of iron oxides to prepare ZVI materials requires high temperatures resulting in high energy consumption and high costs. Biomass can be pyrolyzed at low temperatures to release large amounts of reducing gas, which can efficiently reduce red mud to obtain ZVI at lower temperatures. Therefore, this paper studied the pyrolysis of five biomasses, corn straw, wheat straw, rice husk, pine wood and coffee grounds, and compared the reduction of iron oxide in red mud at different temperatures for different biomass feedstocks. The results showed that the biomass could reduce most of the iron oxide in red mud to ZVI at 800 °C, which was at least 100 °C lower than the conventional iron reduction temperature. The reducing gas greatly facilitated the conversion of iron oxide to ZVI in this process. Moreover, the material has a good removal effect on both gentian violet and methylene blue. A low-energy and low-cost method was explored for the preparation of ZVI materials, and the resource utilization of biomass and red mud was realized.
Assuntos
Ferro , Poluentes Químicos da Água , Biomassa , Pirólise , Compostos FérricosRESUMO
OBJECTIVE: To investigate the prevalence of four common neuropsychiatric disorders in Tibet, with an aim to providing information support to health planning. METHODS: The survey was carried out in four regions of Tibet. The sampling strategy was adapted from that of a national psychiatric epidemiological survey in China in 1982 and 1993. The Neurosis Screening Inventory, Screening Inventory for Alcohol Dependence and Related Problems, Child Intelligence Screening Inventory, and a questionnaire for the Detection of Epileptic Seizures were administered to the respondents through face to face interview. Those with a positive response and 10% of those with a negative response were further interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders (research version) (SCID-I ). Anxiety disorders and alcohol used disorders were diagnosed according to the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV). Hysteria and mental retardation were diagnosed according to the International Classification of Diseases, 10th edition (ICD-10), and the Chinese Classification of Mental Disorders, 3rd edition (CCMD-3). RESULTS: The point prevalence of neuroses, alcohol-related disorders, mental retardation and epilepsy was 2. 56%, 4. 06%, 0. 28% and 0. 68%, respectively. The lifetime prevalence of neuroses, alcohol-related disorders, mental retardation and epilepsy was 2. 62%, 4. 24%, 0. 28% and 0.72%, respectively. CONCLUSION: Alcohol-related disorders and neuroses are the two common mental health problems in Tibet. Mental retardation and epilepsy are the two serious neuropsychiatric disorders affecting Tibetan children and adolescence. These disorders should be identified as priorities in the reginonal health planning in Tibet.
Assuntos
Transtornos Relacionados ao Uso de Álcool/epidemiologia , Epilepsia/epidemiologia , Deficiência Intelectual/epidemiologia , Transtornos Neuróticos/epidemiologia , Adolescente , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos de Amostragem , Inquéritos e Questionários , Tibet/epidemiologia , Adulto JovemRESUMO
Adenosine triphosphate-binding cassette transporter A1 (ABCA1) plays a crucial role in apolipoprotein A-I (apoA-I) binding activity and promotes cellular cholesterol efflux. ApoA-I mimetic peptide D4-F has reported to have the similar ability as apoA-I. However, the detailed mechanisms of ABCA1 regulation by D4-F are not understood. In the present study, we investigated the effects of D4-F on ABCA1 expression and ABCA1-dependent cholesterol efflux and examined the role of Cdc42/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway on the regulation of ABCA1 by D4-F in THP-1 macrophage-derived foam cells. Results showed that D4-F stabilized ABCA1 protein and enhanced ABCA1-dependent cholesterol efflux but had no effect on ABCA1 messenger RNA expression. We also revealed that D4-F enhanced cAMP level and PKA activity and ABCA1 serine phosphorylation. Short interfering RNA of PKA led to reduction of ABCA1 serine phosphorylation and ABCA1-mediated cholesterol efflux compensated by D4-F. PKA-specific activation by PKA agonist enhanced the upregulation of ABCA1 serine phosphorylation and ABCA1-mediated cholesterol efflux by D4-F. However, ABCA1 expression did not change by treatment with PKA agonist or PKA-short interfering RNA. We found that secramine B of Cdc42 inhibitor reduced the cAMP level compensated by D4-F. These results provide evidence that D4-F enhances ABCA1 serine phosphorylation and ABCA1-dependent cholesterol efflux through Cdc42/cAMP/PKA pathway in THP-1 macrophage-derived foam cells.
Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Apolipoproteína A-I/farmacologia , Colesterol/metabolismo , Células Espumosas/efeitos dos fármacos , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transporte Biológico , Linhagem Celular , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ativação Enzimática , Células Espumosas/metabolismo , Expressão Gênica , Humanos , Fosforilação , RNA Mensageiro/biossíntese , Serina/metabolismo , Transdução de Sinais , Fatores de Tempo , Regulação para Cima , Proteína cdc42 de Ligação ao GTP/metabolismoRESUMO
AIM: To determine the effects and potential mechanisms of ibrolipim on ATP-binding membrane cassette transporter A-1 (ABCA1) and ATP-binding membrane cassette transporter G-1 (ABCG1) expression from human macrophage foam cells, which may play a critical role in atherogenesis. METHODS: Human THP-1 cells pre-incubated with ox-LDL served as foam cell models. Specific mRNA was quantified using real-time RT-PCR and protein expression using Western blotting. Cellular cholesterol handling was studied using cholesterol efflux experiments and high performance liquid chromatography assays. RESULTS: Ibrolipim 5 and 50 µmol/L significantly increased cholesterol efflux from THP-1 macrophage-derived foam cells to apoA-I or HDL. Moreover, it upregulated the expression of ABCA1 and ABCG1. In addition, LXRα was also upregulated by the ibrolipim treatment. In addition, LXRα small interfering RNA completely abolished the promotion effect that was induced by ibrolipim. CONCLUSION: Ibrolipim increased ABCA1 and ABCG1 expression and promoted cholesterol efflux, which was mediated by the LXRα signaling pathway.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Benzamidas/farmacologia , Células Espumosas/efeitos dos fármacos , Ativadores de Lipase de Lipoproteínas/farmacologia , Compostos Organofosforados/farmacologia , Receptores Nucleares Órfãos/metabolismo , Transportador 1 de Cassete de Ligação de ATP , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transporte Biológico , Linhagem Celular Tumoral , Proliferação de Células , Colesterol/metabolismo , Células Espumosas/metabolismo , Regulação da Expressão Gênica , Humanos , Receptores X do Fígado , Receptores Nucleares Órfãos/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Regulação para CimaRESUMO
OBJECTIVE: To explore the association of parental rearing style and family dynamic structure with male larcenists. METHODS: A questionnaire survey was undertaken in 280 male imprisoned larcenists and 420 healthy controls with a General Information Questionnaire and EMBU (Egna Minnen Beträlffande Uppfostran). RESULTS: Statistically significant differences were found between the two groups in the following items: 'only child in the family', 'not lived with father before age 5', 'father died', 'mother died', 'both parents died', 'parents divorced', 'lived with father only (mother absence) before age 5', 'adult with father alive (mother died)' and 'adult with mother alive (father died)'. The two groups also experienced significant differences in 'emotional warmth', 'severe punishment', 'over-intervention from both parents', 'favored child from mother', 'father rejection' and 'father over-protection'. CONCLUSION: Men with single father (mother absence) before age 5 and those who have experienced death of any parents, 'emotional warmth', 'severe punishment', 'over-intervention from both parents', 'favored child from mother', 'father rejection' and 'father over-protection' are more likely to commit theft crime.
Assuntos
Educação Infantil/psicologia , Poder Familiar/psicologia , Desenvolvimento da Personalidade , Roubo/psicologia , Adolescente , Pré-Escolar , Família/psicologia , Características da Família , Humanos , Masculino , Relações Pais-Filho , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: The Niemann-Pick C1 (NPC1) protein regulates the transport of cholesterol from late endosomes/lysosomes to other compartments responsible for maintaining intracellular cholesterol homeostasis. Liver X receptors (LXRs) operate as cholesterol sensors which may protect from cholesterol overload by increasing the amount of free cholesterol in the plasma membrane through inducing NPC1 expression. NO-1886 has been proven to be highly effective at increasing liver X receptor alpha expression and promoting cellular cholesterol efflux. In this study, the effects of NO-1886 on NPC1 expression were investigated in THP-1 macrophage-derived foam cells. METHODS AND RESULTS: Results showed that NO-1886 markedly increased expression of NPC1 at both mRNA level and protein level in a dose-dependent and time-dependent manner. Cellular cholesterol content was decreased while cholesterol efflux was increased by NO-1886 treatment. In addition, LXR alpha was also up-regulated by NO-1886 treatment. And LXR alpha small interfering RNA completely abolished the promotion effect which was induced by NO-1886. CONCLUSION: These results provide evidence that NO-1886 up-regulates expression of NPC1 through LXR alpha pathway in THP-1 macrophage- derived foam cells.
Assuntos
Benzamidas/farmacologia , Proteínas de Transporte/biossíntese , Proteínas de Ligação a DNA/fisiologia , Células Espumosas/efeitos dos fármacos , Hipolipemiantes/farmacologia , Glicoproteínas de Membrana/biossíntese , Compostos Organofosforados/farmacologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Proteínas de Transporte/genética , Linhagem Celular , Colesterol/metabolismo , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta a Droga , Células Espumosas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Receptores X do Fígado , Glicoproteínas de Membrana/genética , Proteína C1 de Niemann-Pick , Receptores Nucleares Órfãos , RNA Mensageiro/biossíntese , Receptores Citoplasmáticos e Nucleares/genética , Transdução de Sinais , Fatores de Tempo , Regulação para CimaRESUMO
OBJECTIVE: To explore the role of genetic factors in the brain structural variation by using magnetic resonance imaging scan in schizophrenic patients and their unaffected siblings, and to provide experimental evidence for identifying endophenotype of schizophrenia. METHODS: The optimized voxel-based morphometry (OVBM) was used to process the brain magnetic resonance images in 15 first episode drug-naive schizophrenic patients, 19 unaffected siblings of the patients and 38 normal control subjects. The data were analyzed by using general linear model. RESULTS: Compared to the normal control subjects, significant decreases of gray matter was observed in first episode drug-naive schizophrenia in bilateral temporal lobe, bilateral occipital lobe, left insula, left frontal lobe superior frontal gyrus and right lentiform nucleus medial globus pallidus. Significant increases of gray matter in bilateral parietal lobe, bilateral limbic lobe cingulate gyrus in patients group while compared to controls were also found. In unaffected siblings, significant decreases of gray matter was observed in the right temporal lobe, bilateral occipital lobe, left insula, and left frontal lobe precentral gyrus, and significant increases of gray matter were found in left parietal lobe and bilateral cerebellum posterior lobe. Increased gray matter in left parietal lobe precuneus was found in first episode drug-naive schizophrenia when compared with their unaffected siblings. CONCLUSION: There were similar brain structure abnormalities between the first episode drug-naive schizophrenia and their unaffected siblings. Genetic factor may play important role in brain structural abnormality in schizophrenia, which suggested that the brain structural change might be a genetic endophenotype of schizophrenia.
Assuntos
Encéfalo/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Adulto , Encéfalo/anormalidades , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Esquizofrenia/genética , Esquizofrenia/patologiaRESUMO
OBJECTIVE: To explore the effects of the genetic and environmental factors on intelligence of children and adolescent from the Southwest China Prospective Twin Registry (SCPT). METHODS: The intelligence was investigated by using the Wechsler Intelligence Scale for Children (C-WISC) in 333 twin pairs aged 6-16 years. The effects of genetic and environmental factors on IQ were analyzed by using structural equation modeling (SEM) and correlation analysis method. The effects in different sex and age groups in this population were also investigated. RESULTS: Genetic influence accounted for 0.43 of total IQ variance and 0.37 of verbal IQ in 6-16 years old children and adolescent, but there was no significant genetic effect on performance IQ. The heritability of children aged 10-16 years was higher than that of those aged 6-10 years (total IQ: 0.82 vs 0.00, verbal IQ: 0.80 vs 0.00, performance IQ:0.51 vs 0.00). In males the heritability of verbal IQ (0.47) was higher than that in females (0.05). The shared environmental influences accounted fo r the majority of variance of performance IQ in both males and females. CONCLUSION: There is moderate heritability on the total IQ and verbal IQ, while shared environmental factors played important roles on the variance of performance IQ. The heritability of IQ, verbal IQ and performance IQ are higher in older children and adolescent than that in younger children.
Assuntos
Meio Ambiente , Inteligência/genética , Desempenho Psicomotor/fisiologia , Tempo de Reação/genética , Gêmeos/genética , Adolescente , Fatores Etários , Criança , Desenvolvimento Infantil/fisiologia , Feminino , Humanos , Masculino , Caracteres Sexuais , Fatores Sexuais , Escalas de WechslerRESUMO
ATP binding cassette transporter G1 (ABCG1) is a membrane half-transporter which is the member of ATP-binding cassette (ABC) transporter super-family, it has an important role of regulating the cholesterol and phospholipids effluence. ABCG1 and ABCA1 synergize to mediate cholesterol effluence to HDL (high density lipoprotein). The expression of ABCG1 is mainly regulated by the liver X receptor/the lactochrome receptor system (LXR/RXR). Although the ABCG1 plays an important role in balancing the lipids, its role in cardiovascular disease (CVD) in the animal studies is still controversial. The issue focuses the ABCG1 on the structure, the function, the regulation and the contribution to CVD.