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1.
Environ Res ; 252(Pt 3): 119044, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38697599

RESUMEN

Rising temperatures can increase the risk of mental disorders. As climate change intensifies, the future disease burden due to mental disorders may be underestimated. Using data on the number of daily emergency department visits for mental disorders at 30 hospitals in Beijing, China during 2016-2018, the relationship between daily mean temperature and such visits was assessed using a quasi-Poisson model integrated with a distributed lag nonlinear model. Emergency department visits for mental disorders attributed to temperature changes were projected using 26 general circulation models under four climate change scenarios. Stratification analyses were then conducted by disease subtype, sex, and age. The results indicate that the temperature-related health burden from mental disorders was projected to increase consistently throughout the 21st century, mainly driven by high temperatures. The future temperature-related health burden was higher for patients with mental disorders due to the use of psychoactive substances and schizophrenia as well as for women and those aged <65 years. These findings enhance our knowledge of how climate change could affect mental well-being and can be used to advance and refine targeted approaches to mitigating and adapting to climate change with a view on addressing mental disorders.

2.
World J Gastrointest Oncol ; 16(4): 1626-1646, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38660634

RESUMEN

BACKGROUND: Human-derived gastric cancer organoids (GCOs) are widely used in gastric cancer research; however, the culture success rate is generally low. AIM: To explore the potential influencing factors, and the literature on successful culture rates of GCOs was reviewed using meta-analysis. METHODS: PubMed, Web of Science, and EMBASE were searched for studies. Two trained researchers selected the studies and extracted data. STATA 17.0 software was used for meta-analysis of the incidence of each outcome event. The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies. Funnel plots and Egger's test were used to detect publication bias. Subgroup analyses were conducted for sex, tissue source, histological classification, and the pathological tumor-node-metastasis (pTNM) cancer staging system. RESULTS: Eight studies with a pooled success rate of 66.6% were included. GCOs derived from women and men had success rates of 67% and 46.7%, respectively. GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9% and 53.7%, respectively. GCOs of poorly-differentiated, moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%, 31%, and 32.7%, respectively. GCOs with pTNM stages I-II and III-IV showed success rates of 38.3% and 65.2%, respectively. Y-27632 and non-Y-27632 use showed success rates of 58.2% and 70%, respectively. GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE (72.1% vs 71%, respectively). EDTA digestion showed a 50% lower success rate than other methods (P = 0.04). CONCLUSION: GCO establishment rate is low and varies by sex, tissue source, histological type, and pTNM stage. Omitting Y-27632, and using Liberase TH, TrypLE, or collagenase yields greater success than EDTA.

3.
World J Gastroenterol ; 30(8): 969-983, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38516239

RESUMEN

BACKGROUND: Three-dimensional organoid culture systems have been established as a robust tool for elucidating mechanisms and performing drug efficacy testing. The use of gastric organoid models holds significant promise for advancing personalized medicine research. However, a comprehensive bibliometric review of this bur-geoning field has not yet been published. AIM: To analyze and understand the development, impact, and direction of gastric organoid research using bibliometric methods using data from the Web of Science Core Collection (WoSCC) database. METHODS: This analysis encompassed literature pertaining to gastric organoids published between 2010 and 2023, as indexed in the WoSCC. CiteSpace and VOSviewer were used to depict network maps illustrating collaborations among authors, institutions and keywords related to gastric organoid. Citation, co-citation, and burst analysis methodologies were applied to assess the impact and progress of research. RESULTS: A total of 656 relevant studies were evaluated. The majority of research was published in gastroenterology-focused journals. Globally, Yana Zavros, Hans Clevers, James M Wells, Sina Bartfeld, and Chen Zheng were the 5 most productive authors, while Hans Clevers, Huch Meritxell, Johan H van Es, Marc Van de Wetering, and Sato Toshiro were the foremost influential scientists in this area. Institutions from the University Medical Center Utrecht, Netherlands Institute for Developmental Biology (Utrecht), and University of Cincinnati (Cincinnati, OH, United States) made the most significant contributions. Currently, gastric organoids are used mainly in studies investigating gastric cancer (GC), Helicobacter pylori-infective gastritis, with a focus on the mechanisms of GC, and drug screening tests. CONCLUSION: Key focus areas of research using gastric organoids include unraveling disease mechanisms and enhancing drug screening techniques. Major contributions from renowned academic institutions highlight this field's dynamic growth.


Asunto(s)
Gastritis , Infecciones Intraabdominales , Neoplasias Gástricas , Humanos , Centros Médicos Académicos , Bibliometría
4.
BMC Public Health ; 23(1): 1417, 2023 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-37488590

RESUMEN

OBJECTIVE: This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. METHODS: In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants' residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity . RESULTS: The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: -3.047 to - 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: -258 to - 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: -1.518 to - 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p < 0.05). CONCLUSION: Short-term exposure to PM2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM2.5, the more severe of COPD.


Asunto(s)
Material Particulado , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Beijing , Oscilometría , Estudios Retrospectivos , Pulmón
5.
Metab Brain Dis ; 38(2): 641-655, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36456714

RESUMEN

Sleep deprivation (SD) is prevalent throughout the world, which has negative effects on cognitive abilities, and causing mood alterations. 8-O-acetyl shanzhiside methylester (8-OaS), a chief component in Lamiophlomis rotata (L. rotata) Kudo, possesses potent neuroprotective properties and analgesic effects. Here, we evaluated the alleviative effects of 8-OaS on memory impairment and anxiety in mice subjected to SD (for 72-h). Our results demonstrated that 8-OaS (0.2, 2, 20 mg/kg) administration dose-dependently ameliorated behavioral abnormalities in SD mice, accompanied with restored synaptic plasticity and reduced shrinkage and loss of hippocampal neurons. 8-OaS reduced the inflammatory response and oxidative stress injury in hippocampus caused by SD, which may be related to inhibition of NLRP3 inflammasome-mediated inflammatory process and activation of the Nrf2/HO-1 pathway. SD also led to increases in the expressions of TLR-4/MyD88, active NF-κB, pro-IL-1ß, TNFα and MDA, as well as a decrease in the level of SOD in mice hippocampus, which were reversed by 8-OaS administration. Moreover, our molecular docking analyses showed that 8-OaS also has good affinity for NLRP3 and Nrf2 signaling pathways. These results suggested that 8-OaS could be used as a novel herbal medicine for the treatment of sleep loss and for use as a structural base for developing new drugs.


Asunto(s)
Proteína con Dominio Pirina 3 de la Familia NLR , Privación de Sueño , Animales , Ratones , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , Cognición , Simulación del Acoplamiento Molecular , Factor 2 Relacionado con NF-E2/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Privación de Sueño/complicaciones , Privación de Sueño/tratamiento farmacológico
6.
Plant Sci ; 315: 111145, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35067308

RESUMEN

Flowering time (or heading date in crops) is a critical agronomic trait for rice reproduction and adaptation. The circadian clock is an endogenous oscillator that is involved in controlling photoperiodic flowering. The rice LATE ELONGATED HYPOCOTYL (OsLHY), the core oscillator component of circadian clock, is a homolog of the LHY/CCA1 in Arabidopsis. Here we showed that CRISPR/Cas9-engineered mutations in OsLHY caused late flowering in rice only under natural long-day (nLD) and short-day (nSD) conditions, but not artificial SD (10 h light/14 h dark) conditions. In the oslhy mutant, the diurnal expression of circadian clock-related genes was seriously affected under both LD and SD conditions. Furthermore, the expression of the flowering activators Ehd1, Hd3a and RFT1 was down-regulated and flowering repressors Hd1 and Ghd7 was up-regulated in the oslhy mutant under LD conditions. While the transcripts of flowering-related genes were not dramatically influenced under SD conditions. Dual-luciferase assays showed that OsLHY repressed the transcription of OsGI, Hd1, Ghd7, Hd3a, RFT1 and OsELF3, and activated the transcription of Ehd1. Moreover, the yeast one hybrid assay and electrophoretic mobility shift assay confirmed that OsLHY directly repressed OsGI, RFT1 and OsELF3 by binding to their promoters, which is consistent with that in Arabidopsis. These results suggested that the OsLHY can promote rice flowering mainly through regulating Hd1 and Ehd1.


Asunto(s)
Ritmo Circadiano/fisiología , Flores/crecimiento & desarrollo , Flores/genética , Oryza/crecimiento & desarrollo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , China , Ritmo Circadiano/genética , Productos Agrícolas/genética , Productos Agrícolas/crecimiento & desarrollo , Productos Agrícolas/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Redes y Vías Metabólicas/genética , Fotoperiodo
7.
Front Plant Sci ; 12: 713544, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34421965

RESUMEN

Chloroplasts are crucial organelles for the generation of fatty acids and starch required for plant development. Nascent polypeptide-associated complex (NAC) proteins have been implicated in development as transcription factors. However, their chaperone roles in chloroplasts and their relationship with pollen development in plants remain to be elucidated. Here, we demonstrated that Osj10gBTF3, a NAC protein, regulates pollen and chloroplast development in rice by coordinating with a Hsp90 family chaperone OsHSP82 to mediate chloroplast import. Knockout of Osj10gBTF3 affects pollen and chloroplast development and significantly reduces the accumulation of fertility-related chloroplast protein OsPPR676. Both Osj10gBTF3 and OsHSP82 interact with OsPPR676. Interestingly, the interaction between OsHSP82 and OsPPR676 is only found in the cytoplasm, while the interaction between Osj10gBTF3 and OsPPR676 also occurs inside the chloroplast. The chloroplast stroma chaperone OsCpn60 can also be co-precipitated with Osj10gBTF3, but not with OsHSP82. Further investigation indicates that Osj10gBTF3 enters the chloroplast stroma possibly through the inner chloroplast membrane channel protein Tic110 and then recruits OsCpn60 for the folding or assembly of OsPPR676. Our results reveal a chaperone role of Osj10gBTF3 in chloroplast import different from Hsp90 and provide a link between chloroplast transport and pollen development in rice.

8.
Chin Med J (Engl) ; 134(10): 1175-1180, 2021 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-33883410

RESUMEN

BACKGROUND: Despite almost two decades of well-funded and comprehensive response efforts by the Chinese Government, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) remains a major problem in China. Yet, few studies have recently examined long-term trends in HIV/AIDS prevalence, incidence, and mortality at the national level. This study aimed to determine the prevalence, incidence, and mortality trends for HIV/AIDS over the past 28 years in China. METHODS: We conducted a descriptive, epidemiological, secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 data. To evaluate trends in prevalence, incidence, and mortality over the study period from 1990 to 2017, we calculated values for annual percentage change (APC) and corresponding 95% confidence intervals (CIs) using joinpoint regression analysis. RESULTS: A significant increase in HIV/AIDS prevalence was observed for 1990 to 2009 (APC: 10.7; 95% CI: 10.4, 11.0; P < 0.001), and then remained stable for 2009 to 2017 (APC: 0.7; 95% CI: -0.3, 1.7; P = 0.1). A significant increase in HIV incidence was also observed for 1990 to 2005 (APC: 13.0; 95% CI: 12.6, 13.4; P < 0.001), and then a significant decrease was detected for 2005 to 2017 (APC: -6.5; 95% CI: -7.0, -6.1; P < 0.001). A significant increase in AIDS-related mortality rate was detected for 1990 to 2004 (APC: 10.3; 95% CI: 9.3, 11.3; P < 0.001), followed by a period of stability for 2004 to 2013 (APC: 1.3; 95% CI: -0.7, 3.3; P = 0.2), and then another significant increase for 2013 to 2017 (APC: 15.3; 95% CI: 8.7, 22.2; P < 0.001). CONCLUSIONS: Although prevalence has stabilized and incidence has declined, AIDS-related mortality has risen sharply in recent years. These findings suggest more must be done to bring people into treatment earlier, retain them in treatment more effectively, actively seek to reenter them in treatment if they dropout, and improve the quality of treatment and care regimens.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida/epidemiología , China/epidemiología , Carga Global de Enfermedades , VIH , Infecciones por VIH/epidemiología , Humanos , Incidencia , Prevalencia
9.
Sci Rep ; 10(1): 8616, 2020 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-32451462

RESUMEN

We reported a large Chinese family diagnosed with autosomal dominant tubulointerstitial kidney disease caused by MUC1 mutation (ADTKD-MUC1). Cytosine duplication within a string of 7 cytosines in the variable-number tandem repeats (VNTR) region of the MUC1 gene was detected by long-read single-molecule real-time (SMRT) sequencing. MUC1 frameshift protein (MUC1fs) was found to be expressed in renal tubules and urinary exfoliated cells by pathological examination. The family, which consisted of 5 generations including 137 individuals, was followed for 5 years. Genetic testing was performed in thirty-four individuals, 17 of whom carried MUC1 mutations. The ADTKD-MUC1-affected individuals had an elevated incidence of hyperuricaemia without gout attack. Within five years, higher baseline levels of urinary α1-microglobulin were detected in affected individuals with rapidly progressing renal failure than in affected individuals with stable renal function, and the increases manifested even before increases in serum creatinine. This study demonstrates that SMRT sequencing is an effective method for the identification of MUC1 mutations. The pathological examination of MUC1fs expression in renal tissue and urinary exfoliated cells can contribute to early screening of family members suspected to be affected. It is suggested that affected individuals with elevated urinary α1-microglobulin levels should be closely monitored for renal function.


Asunto(s)
Pueblo Asiatico/genética , Mucina-1/genética , Riñón Poliquístico Autosómico Dominante/diagnóstico , Adulto , Anciano , Estudios de Casos y Controles , China , Femenino , Mutación del Sistema de Lectura , Pruebas Genéticas , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/etiología , Riñón/diagnóstico por imagen , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Linaje , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/patología , Secuencias Repetidas en Tándem/genética , Ultrasonografía , Ácido Úrico/orina , Secuenciación del Exoma
11.
Front Physiol ; 10: 164, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30894818

RESUMEN

Scopoletin is a promising acaricidal botanical natural compound against Tetranychus cinnabarinus, and its acaricidal mechanism maybe involve calcium overload according to our previous study. To seek potential candidate target genes of calcium overload induced by scopoletin in T. cinnabarinus, RNA-seq was utilized to detect changes in transcription levels. 24 and 48 h after treatment, 70 and 102 differentially expressed genes were obtained, respectively. Target genes included 3 signal transduction genes, 4 cell apoptosis genes, 4 energy metabolism genes, and 2 transcription factor genes. The role of 3 calcium signaling pathway-related genes, namely, G-protein-coupled neuropeptide receptor, Bcl-2 protein and guanylate kinase (designated TcGPCR, TcBAG, and TcGUK, respectively) in the calcium overload were investigated in this study. RT-qPCR detection showed that scopoletin treatment upregulated the expression level of TcGPCR and downregulated the expression level of TcBAG and TcGUK. The result of RNAi indicated that downregulation of TcGPCR decreased susceptibility to scopoletin, and downregulation of TcBAG and TcGUK enhanced susceptibility to scopoletin. Functional expression in Chinese hamster ovary cells showed that scopoletin induced a significant increase in intracellular free calcium [Ca2+]i levels by activating TcGPCR. These results demonstrated that the acaricidal mechanism of scopoletin was via disrupting intracellular Ca2+ homeostasis and calcium signaling pathway mediated by GPCR, BAG, and GUK.

12.
Heart ; 105(1): 49-55, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30061161

RESUMEN

OBJECTIVE: Studies investigating the impact of chocolate consumption on cardiovascular disease (CVD) have reached inconsistent conclusions. As such, a quantitative assessment of the dose-response association between chocolate consumption and incident CVD has not been reported. We performed a systematic review and meta-analysis of studies assessing the risk of CVD with chocolate consumption. METHODS: PubMed and EMBASE databases were searched for articles published up to 6 June 2018. Restricted cubic splines were used to model the dose-response association. RESULTS: Fourteen publications (23 studies including 405 304 participants and 35 093 cases of CVD) were included in the meta-analysis. The summary of relative risk (RR) per 20 g/week increase in chocolate consumption was 0.982 (95% CI 0.972 to 0.992, I2=50.4%, n=18) for CVD (heart failure: 0.995 (0.981 to 1.010, I2=36.3%, n=5); total stroke: 0.956 (0.932 to 0.980, I2=25.5%, n=7); cerebral infarction: 0.952 (0.917 to 0.988, I2=0.0%, n=4); haemorrhagic stroke: 0.931 (0.871 to 0.994, I2=0.0%, n=4); myocardial infarction: 0.981 (0.964 to 0.997, I2=0.0%, n=3); coronary heart disease: 0.986 (0.973 to 0.999, n=1)). A non-linear dose-response (pnon-linearity=0.001) indicated that the most appropriate dose of chocolate consumption for reducing risk of CVD was 45 g/week (RR 0.890;95%CI 0.849 to 0.932). CONCLUSIONS: Chocolate consumption may be associated with reduced risk of CVD at <100 g/week consumption. Higher levels may negate the health benefits and induce adverse effects associated with high sugar consumption.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Chocolate , Ingestión de Alimentos/fisiología , Humanos , Medición de Riesgo
13.
Medicine (Baltimore) ; 97(50): e13524, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30558008

RESUMEN

BACKGROUND: Recently, several studies using transcranial sonography (TCS) have demonstrated reduced echogenicity of the mesencephalic midline in unipolar depression and patients with comorbid depression and Parkinson disease (PD). However, there is no consensus on the conclusion that raphe nuclei (RN) hypoechogenicity is associated with depression in PD. The methods used in previous studies lack quantitative and objective indicators to some extent; therefore, the present study used the level of platelet 5-hydroxytryptamine (5-HT) as an objective indicator of depression. Additionally, the reason for the reduced echogenicity of the brainstem raphe is still unclear. OBJECTIVES: The purpose of the present study was to assess the correlation between alterations in RN echogenicity and depressive symptoms in patients with PD using transcranial sonography (TCS). This information could provide a meaningful clinical reference for the antidiastole between depressive symptoms in PD and unipolar depression in patients with PD in whom depressive symptoms occur before motor symptoms. METHODS: TCS was performed in patients with PD, patients with PD and depression, patients with depression and no PD, and healthy controls. Using the red nucleus as a reference, the RN was rated from grades 0 to 1 (grade 0: invisible, slightly echogenic, or interrupted RN; grade 1: hyperechogenicity in the RN observed as a continuous line). RESULTS: The rate of abnormal RN (grade 0) was found to be 16.67% in patients with PD (5/30) and 14.29% in healthy controls (4/28). The presence of abnormal RN was significantly higher (χ = 15.983, P < .05) in patients with depression and PD (40%, 12/30) and in patients with depression only (58.33%, 14/24) than in those without depression and healthy controls. No correlation was found between RN changes and depression severity (P > .05). There were no statistical differences in the concentration of platelet serotonin among the 4 groups (P > .05). CONCLUSIONS: TCS of the mesencephalic midline may be useful for detecting depression, which is an early symptom of PD. However, further neuropathological studies are needed to understand the principles underlying the use of platelet serotonin as a peripheral biomarker, as well as the connection between PD and depression.


Asunto(s)
Trastorno Depresivo/diagnóstico por imagen , Ecoencefalografía/métodos , Enfermedad de Parkinson/psicología , Núcleos del Rafe/diagnóstico por imagen , Plaquetas/química , Estudios de Casos y Controles , Trastorno Depresivo/etiología , Femenino , Humanos , Masculino , Mesencéfalo/diagnóstico por imagen , Persona de Mediana Edad , Enfermedad de Parkinson/patología , Serotonina/sangre
14.
Int Immunopharmacol ; 32: 46-54, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26800097

RESUMEN

Macrophages are heterogeneous and plastic cells which are able to undergo dynamic transition between M1 and M2 polarized phenotypes in response to the microenvironment signals. However, the underlying molecular mechanisms of macrophage polarization are still obscure. In the current study, it was revealed that miR-146a might play a pivotal role in macrophage polarization. As our results indicated, miR-146a was highly expressed in M2 macrophages rather than M1 macrophages. Over-expression of miR-146a resulted in significantly decreased production of pro-inflammatory cytokines including iNOS and TNF-α in M1 macrophages, while increased production of M2 marker genes such as Arg1 and CD206 in M2 macrophages. In contrast, knockdown of miR-146a promoted M1 macrophage polarization but diminished M2 macrophage polarization. Mechanistically, it was revealed that miR-146a modulated macrophage polarization by targeting Notch1. Of note, PPARγ was responsible as another target for miR-146a-mediated macrophage polarization. Taken together, it was suggested that miR-146a might serve as a molecular regulator in macrophage polarization and is a potential therapeutic target for inflammatory diseases.


Asunto(s)
Macrófagos/inmunología , MicroARNs/inmunología , Receptor Notch1/inmunología , Animales , Línea Celular , Interleucina-10/inmunología , Ratones , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , PPAR gamma/inmunología , Factor de Necrosis Tumoral alfa/inmunología
15.
J Nat Prod ; 76(4): 524-9, 2013 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-23586868

RESUMEN

Fostriecin (FST, 1) is a natural product with promising antitumor activity produced by Streptomyces pulveraceus. Its antitumor activity is associated with the selective inhibition of protein phosphatase activities. The biosynthetic gene cluster for FST has recently been cloned and sequenced. To better understand the post-polyketide synthase (PKS) modification steps in the biosynthetic pathway of FST, we constructed and characterized three post-PKS modification gene mutants of fosG, fosK, and fosM by knockout inactivation in S. pulveraceus. As a result, we determined that a fosK-encoded cytochrome P450 monooxygenase is responsible for C-18 hydroxylation, formation of an unsaturated lactone is dependent upon FosM, and the fosG gene product is involved in hydroxylation at C-4 after the action of FosM to yield PD 113,271 from FST. The accumulated analogues from the ΔfosK and ΔfosM mutant strains possessed a malonyl ester moiety that suggested that all the post-PKS modification steps in FST biosynthesis occur with the polyketide chain bearing a malonyl ester at the C-3 position, with formation of the unsaturated six-membered lactone as the last step in FST biosynthesis.


Asunto(s)
Antineoplásicos/aislamiento & purificación , Polienos/aislamiento & purificación , Sintasas Poliquetidas/metabolismo , Pironas/aislamiento & purificación , Streptomyces , Antineoplásicos/química , Antineoplásicos/farmacología , Estructura Molecular , Familia de Multigenes , Resonancia Magnética Nuclear Biomolecular , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Polienos/química , Polienos/farmacología , Pironas/química , Pironas/farmacología , Streptomyces/química , Streptomyces/enzimología , Streptomyces/genética
16.
Zhonghua Nei Ke Za Zhi ; 50(7): 550-4, 2011 Jul.
Artículo en Chino | MEDLINE | ID: mdl-22041263

RESUMEN

OBJECTIVE: To investigate the relationship between the urinary albumin excretion (UAE) and serum uric acid in general population. METHODS: The study participants were derived from the epidemiological study on the association of metabolic syndrome and chronic kidney disease (CKD) in Pinggu district, Beijing. A total of 992 participants (463 men and 529 women) aged from 30 to 75 years were enrolled in this study. For each participant, UAE, serum uric acid, serum creatinine, and serum lipids were detected and other potential risk factors for CKD were surveyed. RESULTS: (1) The frequencies of microalbuminuria, macroalbuminuria and hyperuricemia were 12.9%, 1.8% and 4.3% respectively. The persons with hyperuricemia had significantly higher frequency of albuminuria than those without hyperuricemia (37.2% vs 13.7%, P < 0.01). (2) The participants were divided according to the quartiles (25%, 50%, 75%) of serum uric acid level, and the frequencies of albuminuria in males were 13.2%, 13.9%, 17.2% and 25.4%, while those in females were 8.4%, 6.2%, 9.6% and 24.8%. (3) Multivariate logistic regression analysis showed, hyperuricemia was significantly associated with albuminuria in females (OR = 2.31, 95%CI 1.15-4.68; P = 0.02), but not in males. If the persons with reduced renal function were excluded, similar result still could be gained. CONCLUSIONS: The prevalence of albuminuria increases gradually with uric acid elevation. Serum uric acid is an independent risk factor of elevated UAE, especially in females.


Asunto(s)
Albuminuria/epidemiología , Ácido Úrico/sangre , Adulto , Anciano , Albuminuria/diagnóstico , Creatinina/sangre , Femenino , Humanos , Enfermedades Renales/epidemiología , Enfermedades Renales/metabolismo , Lípidos/sangre , Modelos Logísticos , Masculino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/metabolismo , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Urinálisis
17.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 33(5): 511-6, 2011 Oct.
Artículo en Chino | MEDLINE | ID: mdl-22338134

RESUMEN

OBJECTIVE: To determine the potential urinary biomarkers of metabolic syndrome (MS) with early renal injury and establish diagnostic models by magnetic bead-based separation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). METHODS: Participants were selected from the epidemiologic study on MS and renal involvement among residents in Pinggu district, Beijing. Eight-hour overnight urine samples were fractionated by means of magnetic bead-based weak cation exchange chromatography and subsequently analyzed with MALDI-TOF-MS. Wilcoxon test and random forests were used to screen differential protein peaks of MS patients with early renal injury, then combined with genetic algorithm and support vector machine, respectively, to establish diagnostic models. RESULTS: Totally 54 cases of MS without renal injury and 46 cases of MS with early renal injury were enrolled. Totally twenty protein peaks were up-regulated in the urine of MS patients with early renal injury by Wilcoxon test (P < 0.05); random forests algorithm revealed twelve protein peaks up-regulated in the urine of MS patients with early renal injury (importance value of mean decrease in accuracy > 0.005). Genetic algorithm based model showed 82.6% sensitivity, 84.3% specificity, and 83.5% accuracy by a 10-fold cross-validation in identifying MS patients with early renal injury; correspondingly, the support vector machine based model reported 89.2% sensitivity, 81.1% specificity and 85.5% accuracy. Four protein peaks were included in two diagnostic models with mass-to-charge ratios of 2756.98, 3019.11, 9077.04, and 10 054.26. CONCLUSIONS: The urinary proteome patterns of MS with early renal injury were successfully established with magnetic bead-based separation and MALDI-TOF-MS technology. A series of urinary differential expressing protein peaks were identified with bioinformatics tools. Diagnostic models combining cluster of protein peaks are capable of differentiating MS patients with early renal injury from those without renal injury. The different urine protein excretion patterns revealed in this study provide urinary candidate biomarkers of MS patients with early renal injury for future identification and biological roles investigation.


Asunto(s)
Cromatografía por Intercambio Iónico/métodos , Síndrome Metabólico/orina , Proteoma/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Orina/química , Adulto , Biomarcadores/orina , Femenino , Humanos , Enfermedades Renales/etiología , Enfermedades Renales/orina , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Sensibilidad y Especificidad
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