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1.
FASEB J ; 38(13): e23745, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38923065

RESUMEN

Idiopathic granulomatous mastitis (IGM), a recurrent inflammation disease of the non-lactating breast, has had an increasing clinical morbidity rate in recent years, and its complicated symptoms and unclear etiology make it challenging to treat. This rare benign inflammatory breast disease, centered on the lobules, represents the most challenging type of non-puerperal mastitis (NPM), also known as non-lactating mastitis. In this study, patients diagnosed with IGM (M, n = 23) were recruited as cases, and patients with benign control breast disease (C, n = 17) were enrolled as controls. Cytokine microarray detection measured and analyzed the differentially expressed cytokine factors between IGM and control patients. Then, we verified the mRNA and protein expression levels of the significantly changed cytokine factors using Q-RT-PCR, ELISA, western blot, and IHC experiments. The cytokine factor expression levels significantly changed compared to the control group. We observed a significant increase between IGM and control patients in cytokine factors expression, such as interleukin-1ß (IL-1ß), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1ß, tumor necrosis factor receptor 2 (TNF RII). Then, we verified the expression of these top five dysregulated factors in both mRNA and protein levels. Our results demonstrated the cytokine map in IGM and indicated that several cytokines, especially chemokines, were associated with and significantly dysregulated in IGM tissues compared to the control group. The chemokine factors involved might be essential in developing and treating IGM. These findings would be helpful for a better understanding of IGM and offer valuable insights for devising novel diagnostic and therapeutic strategies.


Asunto(s)
Quimiocinas , Mastitis Granulomatosa , Humanos , Femenino , Mastitis Granulomatosa/metabolismo , Mastitis Granulomatosa/genética , Adulto , Quimiocinas/metabolismo , Quimiocinas/genética , Persona de Mediana Edad , Citocinas/metabolismo , Citocinas/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Estudios de Casos y Controles , Quimiocina CXCL9/metabolismo , Quimiocina CXCL9/genética
2.
BMC Plant Biol ; 24(1): 145, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38413866

RESUMEN

BACKGROUND: Alternative polyadenylation (APA) is an important pattern of post-transcriptional regulation of genes widely existing in eukaryotes, involving plant physiological and pathological processes. However, there is a dearth of studies investigating the role of APA profile in rice leaf blight. RESULTS: In this study, we compared the APA profile of leaf blight-susceptible varieties (CT 9737-613P-M) and resistant varieties (NSIC RC154) following bacterial blight infection. Through gene enrichment analysis, we found that the genes of two varieties typically exhibited distal poly(A) (PA) sites that play different roles in two kinds of rice, indicating differential APA regulatory mechanisms. In this process, many disease-resistance genes displayed multiple transcripts via APA. Moreover, we also found five polyadenylation factors of similar expression patterns of rice, highlighting the critical roles of these five factors in rice response to leaf blight about PA locus diversity. CONCLUSION: Notably, the present study provides the first dynamic changes of APA in rice in early response to biotic stresses and proposes a possible functional conjecture of APA in plant immune response, which lays the theoretical foundation for in-depth determination of the role of APA events in plant stress response and other life processes.


Asunto(s)
Oryza , Xanthomonas , RNA-Seq , Oryza/metabolismo , Poliadenilación/genética , Resistencia a la Enfermedad/genética , Estrés Fisiológico , Xanthomonas/fisiología , Enfermedades de las Plantas/microbiología , Regulación de la Expresión Génica de las Plantas
3.
Int J Mol Sci ; 24(17)2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37686205

RESUMEN

The long non-coding RNA (lncRNA) actin fiber-associated protein-1 antisense RNA 1 (AFAP1-AS1) exerted oncogenic activity in triple-negative breast cancer (TNBC). We designed this study and conducted it to investigate the upstream regulation mechanism of AFAP1-AS1 in TNBC tumorigenesis. In this work, we proved the localization of AFAP1-AS1 in the cytoplasm. We elucidated the mechanism by which the transcription factor specificity protein 1 (SP1) modulated AFAP1-AS1 in TNBC progression, which has yet to be thoroughly studied. Dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay revealed a strong affinity of SP1 toward the promoter regions P3 of AFAP1-AS1, proving the gene expression regulation of AFAP1-AS1 via SP1 in TNBC. Additionally, SP1 could facilitate the tumorigenesis of TNBC cells in vitro and in vivo by regulating the AFAP1-AS1 expression. Furthermore, silenced AFAP1-AS1 suppressed the expression of genes in the mTOR pathway, such as eukaryotic translation initiation factor 4B (EIF4B), mitogen-activated protein kinase-associated protein 1 (MAPKAP1), SEH1-like nucleoporin (SEH1L), serum/glucocorticoid regulated kinase 1 (SGK1), and its target NEDD4-like E3 ubiquitin protein ligase (NEDD4L), and promoted the gene expression of s-phase kinase-associated protein 2 (SKP2). Overall, this study emphasized the oncogenic role of SP1 and AFAP1-AS1 in TNBC and illustrated the AFAP1-AS1 upstream interaction with SP1 and the downstream modulatory of mTOR signaling, thus offering insights into the tumorigenesis mechanism in TNBC.


Asunto(s)
ARN Largo no Codificante , Neoplasias de la Mama Triple Negativas , Humanos , Regulación hacia Arriba/genética , ARN Largo no Codificante/genética , Neoplasias de la Mama Triple Negativas/genética , Serina-Treonina Quinasas TOR/genética , Transformación Celular Neoplásica , Carcinogénesis/genética
4.
BMC Infect Dis ; 21(1): 1245, 2021 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-34903183

RESUMEN

BACKGROUND: Patients with primary brain abscess often present with atypical symptoms, and the outcome varies. We investigated the demographic, laboratory, and neuroimaging features of patients with brain abscess at our hospital and identified factors associated with their outcomes. METHODS: We retrospectively collected the data of patients diagnosed with primary brain abscess at our hospital between January 2011 and December 2020. Their clinical characteristics, predisposing factors, laboratory and neuroimaging findings, treatment, and outcome were analyzed. RESULTS: Of the 57 patients diagnosed with primary abscess, 51 (89.47%) were older than 40 years, and 42 (73.68%) were male. Only eight patients (14.04%) showed the classical triad of headache, fever, and focal neurological deficit. Fifteen patients (26.31%) had comorbidities, of which diabetes mellitus was the most common. Positive intracranial purulent material cultures were obtained in 46.15% of the patients, and gram-negative enteric bacteria were found in 33.33% of them, with Klebsiella pneumoniae being the most frequently observed. Surgical treatment, most commonly in the form of stereotactic drainage, was received by 54.39% of the patients. Good outcomes were achieved in 75.44% of the patients. Multivariate logistic regression analysis showed that patients with headaches were more likely to have a poor outcome (odds ratio 6.010, 95% confidence interval 1.114-32.407, p = 0.037). CONCLUSIONS: Male patients and those older than 40 years were more susceptible to brain abscess than female patients and those younger than 40 years, respectively. Only a few patients showed the classical triad of clinical symptoms. Diabetes mellitus was the most common comorbidity. Positive intracranial specimens' culture results were uncommon, with gram-negative enteric bacteria, especially Klebsiella pneumoniae, being the main organisms found. Most patients had a good outcome, and the presence of headache may influence the outcome.


Asunto(s)
Absceso Encefálico , Klebsiella pneumoniae , Absceso Encefálico/tratamiento farmacológico , Absceso Encefálico/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Oportunidad Relativa , Estudios Retrospectivos
5.
J Stroke Cerebrovasc Dis ; 30(8): 105913, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34130104

RESUMEN

OBJECTIVES: Sleep-disordered breathing adversely impacts stroke outcomes. We investigated whether sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep differentially influenced stroke outcomes. MATERIALS AND METHODS: Acute ischemic stroke patients who finished polysomnography within 14 days of stroke onset from April 2010 to August 2018 were reviewed. Patients were divided into four groups according to apnea-hypopnea index during rapid eye movement sleep and non-rapid eye movement sleep. The modified Rankin Scale was used to evaluate short-term outcome. During January and April 2019, another follow-up was performed for long-term outcomes, including stroke-specific quality-of-life scale, modified Rankin Scale, stroke recurrence and death. RESULTS: Of 140 patients reviewed, 109 were finally recruited. Although patients with sleep-disordered breathing during non-rapid eye movement sleep only and with sleep-disordered breathing during both rapid eye movement sleep and non-rapid eye movement sleep had higher apnea-hypopnea indices and more disrupted sleep structures, short-term and long-term outcomes did not significantly different between four groups. In Logistic regression analysis, apnea-hypopnea index (p = 0.013, OR 1.023, 95%CI 1.005-1.042) was found independently associated with short-term outcome. Rapid eye movement sleep latency (p = 0.045, OR 0.994, 95%CI 0.987-1.000) was found independently associated with quality of life. Apnea-hypopnea indices during rapid eye movement sleep or non-rapid eye movement sleep were not significantly associated with short-term or long-term outcomes. CONCLUSIONS: Apnea-hypopnea index is an independent risk factor of short-term outcome of acute ischemic stroke while sleep-disordered breathing during rapid eye movement sleep and non-rapid eye movement sleep do not affect stroke outcomes differently.


Asunto(s)
Accidente Cerebrovascular Isquémico/complicaciones , Pulmón/fisiopatología , Respiración , Síndromes de la Apnea del Sueño/complicaciones , Sueño REM , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/rehabilitación , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Síndromes de la Apnea del Sueño/diagnóstico , Síndromes de la Apnea del Sueño/fisiopatología , Rehabilitación de Accidente Cerebrovascular , Factores de Tiempo , Resultado del Tratamiento
6.
Nanotechnology ; 31(20): 205403, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32000156

RESUMEN

As a substitute of Pt-based catalysts, MoS2-based catalysts have been widely used in hydrogen evolution reaction, but the inherent low conductivity, limited active edges, self-stacking and agglomeration still hinder their activities. In this work, Mn-doped MoS2 nanosheets were vertically anchored on carbon nanotubes (CNTs) by the one-step hydrothermal reaction, in which Mn-O-C/Mo-O-C was considered as a bridge between Mn-MoS2 and CNTs. The doping of the Mn element enables the spreading of MoS2 on CNTs and the rapid escape of hydrogen bubbles from the electrode, while conductive CNTs with hydrophilicity can accelerate the electron transport process between the electrolyte and the material. With an overpotential of 150 mV at a current density of -10 mA cm-2 and a Tafel slope of 39 mV dec-1, this material exhibited excellent catalytic hydrogen evolution activity, which could open the path for designing commercial electrocatalysts.

7.
Sensors (Basel) ; 20(15)2020 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-32717925

RESUMEN

The online measurement of moisture content for grains is an essential technology to realize real-time tracking and control, improve drying quality and reduce energy consumption of the drying process. To improve the measurement accuracy and reliability of the dynamic measurement process as well as expand the application scope of the device, the present work constructed an experimental equipment for determining dynamic resistance characteristics of a single grain. The relations between moisture content and real-time resistance waveform were revealed, and an analytical calculation method of peak value and peak area of waveform was proposed, which correctly revealed the electrical measurement properties of grain. The results demonstrated that the gap width between the electrodes had large influence on the sensor's performance. Moreover, an online measuring device was developed based on the experimental analysis and calculation method, and the test results in both lab and field for different grains showed that online real-time absolute measurement error are within ±0.5% in the varied moisture content (10-35%w.b.) and the temperature (-20-50 °C). The main results and the developed device might provide technical support for developing intelligent grain drying equipment.

8.
Entropy (Basel) ; 22(6)2020 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-33286461

RESUMEN

The improvement of the design and operation of energy conversion systems is a theme of global concern. As an energy intensive operation, industrial agricultural product drying has also attracted significant attention in recent years. Taking a novel industrial corn drying system with drying capacity of 5.5 t/h as a study case, based on existing exergoeconomic and exergetic analysis methodology, the present work investigated the exergetic and economic performance of the drying system and identified its energy use deficiencies. The results showed that the average drying rate for corn drying in the system is 1.98 gwater/gdry matter h. The average exergy rate for dehydrating the moisture from the corn kernel is 345.22 kW and the exergy efficiency of the drying chamber ranges from 14.81% to 40.10%. The average cost of producing 1 GJ exergy for removing water from wet corn kernels is USD 25.971, while the average cost of removing 1 kg water is USD 0.159. These results might help to further understand the drying process from the exergoeconomic perspective and aid formulation of a scientific index for agricultural product industrial drying. Additionally, the results also indicated that, from an energy perspective, the combustion chamber should be firstly optimized, while the drying chamber should be given priority from the exergoeconomics perspective. The main results would be helpful for further optimizing the drying process from both energetic and economic perspectives and provide new thinking about agricultural product industrial drying from the perspective of exergoeconomics.

9.
Neurol Sci ; 40(9): 1855-1863, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31055730

RESUMEN

OBJECTIVE: To investigate the association of homocysteine (Hcy), folate, and white matter hyperintensities in Parkinson's disease (PD) with different motor phenotypes. METHODS: Of the PD patients, 176 were included. Based on the Unified Parkinson's Disease Rating Scale, the PD patients were classified into postural instability gait disorder (PIGD) and non-PIGD phenotypes. According to the Fazekas score, patients were divided into the none/mild white matter hyperintensity (WMH) group and the moderate/severe WMH group. The relationship of Hcy, folate, and white matter hyperintensities (WMHs), and the motor phenotype of PD were analyzed. RESULTS: PD-PIGD patients had higher proportion of moderate/severe WMHs, Hcy levels, and lower folate levels than PD-non-PIGD patients (p all ≤ 0.001). In the subgroup analysis, patients with both PD-PIGD and moderate/severe WMHs had the highest Hcy and lowest folate levels compared with others. Binary logistic regression analysis showed that age, folate, and Hcy were independent risk factors for WMHs. In an a priori-determined stratified analysis, after adjustment for confounding factors, the odds ratio of WMHs was 8.01 (95% CI 2.700-23.767, p trend = 0.001) in the patients with Hcy levels in the highest quintile compared with the lowest quintile and 16.81 (95% CI 4.74-59.65, p trend < 0.001) in the patients with folate levels in the lowest quintile compared with the highest quintile. CONCLUSIONS: Our data showed a close association between WMHs and Hcy, folate especially in PD-PIGD patients. It can be speculated that higher Hcy and lower folate probably played important roles in the development of WMHs and motor heterogeneity in PD.


Asunto(s)
Ácido Fólico/sangre , Trastornos Neurológicos de la Marcha , Homocisteína/sangre , Enfermedad de Parkinson , Equilibrio Postural/fisiología , Sustancia Blanca/patología , Anciano , Femenino , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Índice de Severidad de la Enfermedad , Sustancia Blanca/diagnóstico por imagen
10.
Sleep Breath ; 23(2): 455-462, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30145676

RESUMEN

PURPOSE: Post-stroke cognitive impairment (PSCI) is common among stroke survivors, although its risk factors are not well understood. Here, we assessed cognitive function in patients within 14 days after minor stroke and investigated the risk factors of PSCI, including sleep-related factors. METHODS: Patients with minor acute ischemic stroke (n = 86) were continuously recruited from November 2015 to October 2016. Demographic and clinical data were collected, and cognitive assessment and polysomnography were performed. Based on their cognitive performance, stroke patients were divided into PSCI and no PSCI groups. Age-, sex-, and education-matched participants (n = 36) were included as a healthy control (HC) group. RESULTS: Stroke patients showed impairments in multiple cognitive domains relative to HC participants (p < 0.01). Among stroke patients, the prevalence of PSCI and obstructive sleep apnea was 81.4 and 74.4%, respectively. Impairments in attention and working memory (87.1%) and executive function (84.3%) were the most common among stroke patients. Compared with no PSCI patients, PSCI patients showed a higher prevalence of obstructive sleep apnea (50.0 vs. 80.0%, p = 0.030) and shorter total sleep time (435.1 ± 104.0 vs. 347.3 ± 98.1 min, p = 0.002). Logistic regression analysis showed that education duration, total sleep time, and lowest SaO2 were independent risk factors for PSCI. CONCLUSIONS: The prevalence of PSCI is high after minor ischemic stroke. In particular, attention and working memory and executive function are most commonly impaired. Although the risk factors for PSCI are numerous, shorter total sleep time and degree of hypoxia at night warrant further attention.


Asunto(s)
Isquemia Encefálica/complicaciones , Disfunción Cognitiva/etiología , Apnea Obstructiva del Sueño/etiología , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Atención , Función Ejecutiva , Femenino , Humanos , Hipoxia/etiología , Masculino , Memoria a Corto Plazo , Persona de Mediana Edad , Pruebas Neuropsicológicas , Polisomnografía , Estudios Prospectivos , Factores de Riesgo
11.
Pain Pract ; 18(1): 29-37, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28371220

RESUMEN

OBJECTIVES: Both sleep disorders and pain decrease quality of life in patients with Parkinson's disease (PD). However, little is known about the relationship between objective sleep disturbances and pain in patients with PD. This study aimed to (1) examine the clinical characteristics of pain in PD patients and (2) explore the correlation between pain and sleep disturbances in PD patients. METHODS: Parkinson's disease patients (N = 144) underwent extensive clinical evaluations of motor and nonmotor symptoms and characteristics of pain. Overnight video-polysomnography was also conducted. Clinical characteristics and sleep parameters were compared between PD patients with or without pain. RESULTS: Pain was reported by 75 patients (52.1%), with 49 (65.3%) reporting pain of at least moderate severity. PD patients with pain were older and had longer disease duration, more severe PD symptoms as assessed by Hoehn and Yahr stage and the Unified Parkinson's Disease Rating Scale, and higher L-dopa equivalent daily dose compared with PD patients without pain. PD patients with pain also showed significantly decreased sleep efficiency (57.06% ± 15.84% vs. 73.80% ± 12.00%, P < 0.001), increased nonrapid eye movement stage 1 (N1) sleep (33.38% ± 19.32% vs. 17.84% ± 8.48%, P < 0.001), and decreased rapid eye movement sleep (12.76% ± 8.24% vs. 16.06% ± 6.53%, P = 0.009). Binary logistic regression analysis revealed that poorer activities of daily living, depressed mood, higher percentage of N1 sleep, and lower sleep efficiency were independent predictors of pain in patients with PD. CONCLUSIONS: Musculoskeletal pain is the most common type of pain in patients with PD. Disrupted sleep continuity, altered sleep architecture, depressed mood, and compromised activities of daily living may be associated with pain in patients with PD.


Asunto(s)
Dolor/epidemiología , Enfermedad de Parkinson/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Actividades Cotidianas , Anciano , Antiparkinsonianos/uso terapéutico , Depresión/epidemiología , Depresión/psicología , Femenino , Humanos , Levodopa/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Dolor Musculoesquelético/epidemiología , Dolor Musculoesquelético/fisiopatología , Dolor Musculoesquelético/psicología , Dolor/fisiopatología , Dolor/psicología , Dimensión del Dolor , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Polisomnografía , Calidad de Vida , Sueño , Trastornos del Sueño-Vigilia/fisiopatología , Sueño REM
12.
Exp Cell Res ; 346(2): 241-7, 2016 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-27292312

RESUMEN

Berberine (BBR) exerts powerful renoprotective effects on diabetic nephropathy (DN), but the underlying mechanisms remain unclear. We previously demonstrated that activation of the G protein-coupled bile acid receptor TGR5 ameliorates diabetic nephropathy by inhibiting the activation of the sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 2 (S1P2) signaling pathway. In this study, we explored the role of TGR5 in the BBR-induced downregulation of sphingosine 1-phosphate receptor 2 (S1P2)/mitogen-activated protein kinase (MAPK)-mediated fibrosis in glomerular mesangial cells (GMCs). Results showed that, BBR suppressed the expression of FN, ICAM-1, and TGF-ß1 in high-glucose cultures of GMCs, and the phosphorylation level of c-Jun/c-Fos was downregulated. The high glucose lowered TGR5 expression in a time-dependent manner; this effect was reversed by BBR in a dose-dependent manner. The TGR5 agonist INT-777 decreased the high glucose-induced FN, ICAM-1, and TGF-ß1 protein contents. In addition, TGR5 siRNA blocked S1P2 degradation by BBR. And MAPK signaling, which plays important regulatory roles in the pathological progression of DN, was activated by TGR5 siRNA. Apart from this, MAPK signaling as well as FN, ICAM-1, and TGF-ß1 suppressed by BBR under high glucose conditions were limited by TGR5 depletion. Thus, BBR decreases FN, ICAM-1, and TGF-ß1 levels under high glucose conditions in GMCs possibly by activating TGR5 and inhibiting S1P2/MAPK signaling.


Asunto(s)
Berberina/farmacología , Glucosa/toxicidad , Glomérulos Renales/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Mesangiales/metabolismo , Células Mesangiales/patología , Receptores de Lisoesfingolípidos/metabolismo , Animales , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Fibronectinas/metabolismo , Fibrosis , Técnicas de Silenciamiento del Gen , Molécula 1 de Adhesión Intercelular/metabolismo , Células Mesangiales/efectos de los fármacos , Fosforilación/efectos de los fármacos , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Factor de Transcripción AP-1/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
13.
Cardiovasc Diabetol ; 15: 19, 2016 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-26833058

RESUMEN

BACKGROUND: Abnormalities in lipid and glucose metabolism are constantly observed in type 2 diabetes. However, these abnormalities can be ameliorated by polydatin. Considering the important role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in metabolic diseases, we explore the possible mechanism of polydatin on lipid and glucose metabolism through its effects on PCSK9. METHODS: An insulin-resistant HepG2 cell model induced by palmitic acid (PA) and a db/db mice model were used to clarify the role of polydatin on lipid and glucose metabolism. RESULTS: In insulin-resistant HepG2 cells, polydatin upregulated the protein levels of LDLR and GCK but repressed PCSK9 protein expression, besides, polydatin also inhibited the combination between PCSK9 and LDLR. Knockdown and overexpression experiments indicated that polydatin regulated LDLR and GCK expressions through PCSK9. In the db/db mice model, we found that polydatin markedly enhanced GCK and LDLR protein levels, and inhibited PCSK9 expression in the liver. Molecular docking assay was further performed to analyze the possible binding mode between polydatin and the PCSK9 crystal structure (PDB code: 2p4e), which indicated that steady hydrogen bonds formed between polydatin and PCSK9. CONCLUSIONS: Our study indicates that polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating PCSK9.


Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Glucósidos/farmacología , Hepatocitos/efectos de los fármacos , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Proproteína Convertasas/metabolismo , Serina Endopeptidasas/metabolismo , Estilbenos/farmacología , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo , Medicamentos Herbarios Chinos/metabolismo , Femenino , Quinasas del Centro Germinal , Glucósidos/metabolismo , Células Hep G2 , Hepatocitos/enzimología , Humanos , Enlace de Hidrógeno , Hipoglucemiantes/metabolismo , Lípidos/sangre , Hígado/enzimología , Ratones , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Ácido Palmítico/farmacología , Proproteína Convertasa 9 , Proproteína Convertasas/química , Proproteína Convertasas/genética , Unión Proteica , Conformación Proteica , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Interferencia de ARN , Receptores de LDL/genética , Receptores de LDL/metabolismo , Serina Endopeptidasas/química , Serina Endopeptidasas/genética , Estilbenos/metabolismo , Factores de Tiempo , Transfección
14.
Pharmacol Res ; 111: 226-236, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27317945

RESUMEN

Glucose and lipid metabolism disorders and chronic inflammation in the kidney tissues are largely responsible for causative pathological mechanism of renal fibrosis in diabetic nephropathy (DN). As our previous findings confirmed that, sphingosine 1-phosphate (S1P)/sphingosine 1-phosphate receptor 2 (S1P2) signaling activation promoted renal fibrosis in diabetes. Numerous studies have demonstrated that the G protein-coupled bile acid receptor TGR5 exhibits effective regulation of glucose and lipid metabolism and anti-inflammatory effects. TGR5 is highly expressed in kidney tissues, whether it attenuates the inflammation and renal fibrosis by inhibiting the S1P/S1P2 signaling pathway would be a new insight into the molecular mechanism of DN. Here we investigated the effects of TGR5 on diabetic renal fibrosis, and the underlying mechanism would be also discussed. We found that TGR5 activation significantly decreased the expression of intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-ß1), as well as fibronectin (FN) induced by high glucose in glomerular mesangial cells (GMCs), which were pathological features of DN. S1P2 overexpression induced by high glucose was diminished after activation of TGR5, and AP-1 activity, including the phosphorylation of c-Jun/c-Fos and AP-1 transcription activity, was attenuated. As a G protein-coupled receptor, S1P2 interacted with TGR5 in GMCs. Furthermore, INT-777 lowered S1P2 expression and promoted S1P2 internalization. Taken together, TGR5 activation reduced ICAM-1, TGF-ß1 and FN expressions induced by high glucose in GMCs, the mechanism might be through suppressing S1P/S1P2 signaling, thus ameliorating diabetic nephropathy.


Asunto(s)
Ácidos Cólicos/farmacología , Nefropatías Diabéticas/prevención & control , Glucosa/toxicidad , Lisofosfolípidos/metabolismo , Células Mesangiales/efectos de los fármacos , Receptores Acoplados a Proteínas G/agonistas , Receptores de Lisoesfingolípidos/metabolismo , Transducción de Señal/efectos de los fármacos , Esfingosina/análogos & derivados , Animales , Células Cultivadas , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Modelos Animales de Enfermedad , Fibronectinas/metabolismo , Fibrosis , Molécula 1 de Adhesión Intercelular/metabolismo , Células Mesangiales/metabolismo , Células Mesangiales/patología , Ratones Endogámicos C57BL , Fosforilación , Interferencia de ARN , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato , Factor de Transcripción AP-1/metabolismo , Transfección , Factor de Crecimiento Transformador beta1/metabolismo
15.
J Pharmacol Sci ; 132(1): 15-23, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27094369

RESUMEN

This study was aimed to investigate the crosstalk between protein kinase C ζ (PKCζ) and signal transducer and activator of transcription 3 (STAT3) in cardiomyocyte hypertrophy. In neonatal rat cardiomyocyte hypertrophic model induced by phenylephrine (PE), the levels of phosphorylated PKCζ and phosphorylated STAT3 were significantly increased, suggesting the activation of both PKCζ and STAT3 in cardiomyocyte hypertrophy. Overexpression of PKCζ by adenovirus infection elevated the expressions of hypertrophic markers atrial natriuretic factor (ANF) and brains natriuretic polypeptide (BNP), as well as the cell surface area; while genetic silencing of PKCζ inhibited PE-induced cardiomyocyte hypertrophy. An interaction between PKCζ and STAT3 in cardiomyocytes was shown by co-immunoprecipitation experiments. Overexpression of PKCζ increased the phosphorylated level of STAT3 at both Ser727 and Tyr705, promoted the nuclear translocation of STAT3, and enhanced the expression of STAT3 downstream target genes c-fos and angiotensinogen (aGT); whereas PKCζ knockdown prevented PE-induced STAT3 activation, nuclear shuttling and transcriptional activation. In conclusion, PKCζ interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy. Strategies targeting inhibition of PKCζ-STAT3 signaling pathway suggest a therapeutic potential for cardiac hypertrophy.


Asunto(s)
Cardiomegalia/metabolismo , Miocitos Cardíacos/metabolismo , Proteína Quinasa C/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Células Cultivadas , Proteínas Fluorescentes Verdes/genética , Fenilefrina/farmacología , Fosforilación , Plásmidos , Proteína Quinasa C/genética , ARN Interferente Pequeño/genética , Ratas , Ratas Sprague-Dawley , Factor de Transcripción STAT3/genética
16.
Sleep Breath ; 20(4): 1285-1292, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27259748

RESUMEN

PURPOSE: Retinal nerve fiber layer (RNFL) thinning occurs in Parkinson's disease (PD) and other neurodegenerative diseases. Idiopathic RBD (iRBD) is a well-established prodromal hallmark of synucleinopathies and occurs secondary to many neurodegenerative diseases, including PD. The aim of this study is to determine whether or not retinal structures are altered with the onset of rapid eye movement (REM) sleep behavior disorders (RBD). METHODS: In all, a total of 63 patients with PD, 14 patients with idiopathic RBD, and 26 sex- and age-matched healthy controls were enrolled and underwent optical coherence tomography measurements (HD-OCT (Zeiss) ) for the average and every quadrant of RNFL thickness. The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to classify PD patients with clinically probable RBD (PD + pRBD) or without probable RBD (PD - pRBD). Patients with iRBD were identified by polysomnography. RESULTS: For patients with RBD (idiopathic or secondary to PD), we found a significant decrease in RNFL thickness compared with groups without RBD (PD - pRBD and healthy controls) (all p < 0.05). Average RNFL thickness in patients with iRBD is significantly thinner than in healthy controls (p < 0.05). In PD, the average RNFL thickness was dramatically thinner in the PD + pRBD group than the PD - pRBD group (p < 0.005). Compared with healthy controls, RNFL thickness was slightly thinner in the drug-naive PD group but not the PD group with drug treatment. Multiple linear regression analysis showed that RBDSQ score was negatively associated with average and inferior RNFL variation in PD (all p < 0.005). CONCLUSIONS: The findings show that RNFL was slightly but significantly thinner in idiopathic RBD. In PD, RNFL thickness may vary depending on the presence of RBD.


Asunto(s)
Fibras Nerviosas/patología , Enfermedades Neurodegenerativas/patología , Enfermedad de Parkinson/patología , Trastorno de la Conducta del Sueño REM/patología , Retina/patología , Sueño REM/fisiología , Tomografía de Coherencia Óptica , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía , Valores de Referencia , Encuestas y Cuestionarios
17.
Phys Rev Lett ; 115(19): 195503, 2015 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-26588397

RESUMEN

The macroscopic control of ubiquitous heat flow remains poorly explored due to the lack of a fundamental theoretical method. Here, by establishing temperature-dependent transformation thermotics for treating materials whose conductivity depends on temperature, we show analytical and simulation evidence for switchable thermal cloaking and a macroscopic thermal diode based on the cloaking. The latter allows heat flow in one direction but prohibits the flow in the opposite direction, which is also confirmed by our experiments. Our results suggest that the temperature-dependent transformation thermotics could be a fundamental theoretical method for achieving macroscopic heat rectification, and it could provide guidance both for the macroscopic control of heat flow and for the design of the counterparts of switchable thermal cloaks or macroscopic thermal diodes in other fields like seismology, acoustics, electromagnetics, and matter waves.


Asunto(s)
Modelos Teóricos , Termografía/métodos , Simulación por Computador , Transferencia de Energía , Temperatura , Conductividad Térmica
18.
Exp Cell Res ; 327(2): 276-86, 2014 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-25064462

RESUMEN

RhoA/Rho kinase (ROCK) signaling has been suggested to be involved in diabetic nephropathy (DN) pathogenesis. Altered expression of connexin43 (Cx43) has been found in kidneys of diabetic animals. Both of them have been found to regulate nuclear factor kappa-B (NF-κB) activation in high glucose-treated glomerular mesangial cells (GMCs). The aim of this study was to investigate the relationship between RhoA/ROCK signaling and Cx43 in the DN pathogenesis. We found that upregulation of Cx43 expression inhibited NF-κB p65 nuclear translocation induced by RhoA/ROCK signaling in GMCs. Inhibition of RhoA/ROCK signaling attenuated the high glucose-induced decrease in Cx43. F-actin accumulation and an enhanced interaction between zonula occludens-1 (ZO-1) and Cx43 were observed in high glucose-treated GMCs. ZO-1 depletion or disruption of F-actin formation also inhibited the reduction in Cx43 protein levels induced by high glucose. In conclusion, activated RhoA/ROCK signaling induces Cx43 degradation in GMCs cultured in high glucose, depending on F-actin regulation. Increased F-actin induced by RhoA/ROCK signaling promotes the association between ZO-1 and Cx43, which possibly triggered Cx43 endocytosis, a mechanism of NF-κB activation in high glucose-treated GMCs.


Asunto(s)
Conexina 43/metabolismo , Glucosa/farmacología , Células Mesangiales/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína de la Zonula Occludens-1/metabolismo , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Inmunoprecipitación , Masculino , Células Mesangiales/citología , Células Mesangiales/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Edulcorantes/farmacología
19.
Environ Monit Assess ; 186(9): 5763-75, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24869949

RESUMEN

Blackfoot disease (BFD) had occurred seriously in the Yichu, Hsuehchia, Putai, and Peimen townships of Chia-Nan District of Taiwan in the early days. These four townships are the districts of fishpond cultivation domestically in Taiwan. Groundwater becomes the main water supply because of short income in surface water. The problems of over pumping in groundwater may not only result in land subsidence and seawater intrusion but also be harmful to the health of human giving rise to the bioaccumulation via food chain in groundwater with arsenic (As). This research uses sequential indicator simulation (SIS) to characterize the spatial arsenic distribution in groundwater in the four townships. Risk assessment is applied to explore the dilution ratio (DR) of groundwater utilization, which is defined as the ratio showing the volume of groundwater utilization compared to pond water, for fish farming in the range of target cancer risk (TR) especially on the magnitude of 10(-4)~10(-6). Our study results reveal that the 50th percentile of groundwater DRs served as a regulation standard can be used to perform fish farm groundwater management for a TR of 10(-6). For a TR of 5 × 10(-6), we suggest using the 75th percentile of DR for groundwater management. For a TR of 10(-5), we suggest using the 95th percentile of the DR standard for performing groundwater management in fish farm areas. For the TR of exceeding 5 × 10(-5), we do not suggest establishing groundwater management standards under these risk standards. Based on the research results, we suggest that establishing a TR at 10(-5) and using the 95th percentile of DR are best for groundwater management in fish farm areas.


Asunto(s)
Acuicultura , Monitoreo del Ambiente , Agua Subterránea/química , Estanques/química , Contaminantes Químicos del Agua/análisis , Animales , Arsénico/análisis , Peces/crecimiento & desarrollo , Cadena Alimentaria , Humanos , Medición de Riesgo , Taiwán , Contaminación Química del Agua/prevención & control , Abastecimiento de Agua
20.
Biomed Pharmacother ; 172: 116241, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38330711

RESUMEN

OBJECTIVE: Pathologic cardiac hypertrophy (PCH) is a precursor to heart failure. Amydrium sinense (Engl.) H. Li (AS), a traditional Chinese medicinal plant, has been extensively utilized to treat chronic inflammatory diseases. However, the therapeutic effect of ASWE on PCH and its underlying mechanisms are still not fully understood. METHODS: A cardiac hypertrophy model was established by treating C57BL/6 J mice and neonatal rat cardiomyocytes (NRCMs) in vitro with isoprenaline (ISO) in this study. The antihypertrophic effects of AS water extract (ASWE) on cardiac function, histopathologic manifestations, cell surface area and expression levels of hypertrophic biomarkers were examined. Subsequently, the impact of ASWE on inflammatory factors, p65 nuclear translocation and NF-κB activation was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that oral administration of ASWE effectively improved ISO-induced cardiac hypertrophy in mice, as evidenced by histopathological manifestations and the expression levels of hypertrophic markers. Furthermore, the in vitro experiments demonstrated that ASWE treatment inhibited cardiac hypertrophy and suppressed inflammation response in ISO-treated NRCMs. Mechanically, our findings provided evidence that ASWE suppressed inflammation response by repressing p65 nuclear translocation and NF-κB activation. ASWE was found to possess the capability of inhibiting inflammation response and cardiac hypertrophy induced by ISO. CONCLUSION: To sum up, ASWE treatment was shown to attenuate ISO-induced cardiac hypertrophy by inhibiting cardiac inflammation via preventing the activation of the NF-kB signaling pathway. These findings provided scientific evidence for the development of ASWE as a novel therapeutic drug for PCH treatment.


Asunto(s)
Araceae , FN-kappa B , Animales , Ratones , Ratas , Ratones Endogámicos C57BL , Isoproterenol/toxicidad , Transducción de Señal , Iones , Litio , Artesunato , Cardiomegalia/inducido químicamente , Cardiomegalia/tratamiento farmacológico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico
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