Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
Nat Prod Res ; : 1-6, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37876186

RESUMEN

Two previously undescribed natural cyathane diterpenoids Me-dentifragilin A (1) and Epi-neocyathin O (2), and three known cyathane diterpenoids 3-5, cyathin O, neocyathin P, and cyathin I, were isolated from the rice medium of the Cyathus striatus CBPFE A06. Their structures were established by NMR spectra, and HR-ESI-MS. Compounds 1-5 displayed encouraging neurotrophic activity in PC-12 cells at doses of 5 µM. Meanwhile, 1-5 significantly inhibited LPS-induced NO generation in BV2 cells with the IC50 values ranging from 2.44 ± 0.16 to 4.33 ± 0.32 µM. Western blot analysis showed that 2 and 4 inhibited the expression of genes involved in nitric oxide (NO) production. Molecular docking revealed that five residues of inducible NO synthase (iNOS) are key residues affecting the interaction of 2 and 4 with iNOS. This study enriches the structural diversity of cyathane diterpenes and adds to the evidence that cyathane diterpenes prevent and treat neurodegenerative diseases.

2.
BMC Nephrol ; 21(1): 252, 2020 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-32616008

RESUMEN

BACKGROUND: According to the "lipid nephrotoxicity hypothesis", there is now significant research being conducted in this area. By studying the role of hyperlipidemia in chronic kidney disease in the general Zhejiang population, we aimed to explore the correlation between changes in blood lipid levels and chronic kidney disease. METHODS: We collected and analyzed clinical data from ordinary residents who participated in the annual comprehensive physical examination with no overt kidney disease in Zhejiang Provincial People's Hospital, China from January 2011 to December 2016. According to triglyceride, total cholesterol and low-density lipoprotein levels, participants were respectively divided into 4 groups. Statistical methods were used to evaluate the correlation between different blood lipid profiles and chronic kidney disease. RESULTS: Five thousand one hundred eighty-three participants were included in our study. During the six-year follow-up period, 227 participants (4.4%) developed chronic kidney disease. The odds ratio for incident chronic kidney disease was 3.14 (95%CI: 1.53-6.43) in Q3, 3.84 (95%CI: 1.90-7.76) in Q4 according to the total cholesterol group and 1.17 (95%CI: 1.04-1.32) in Q3, 1.40 (95%CI: 1.11-2.48) in Q4 according to the low-density lipoprotein group, respectively, after multivariable-adjusted analyses. According to the triglyceride grouping, the odds ratio for incident chronic kidney disease was 2.88 (95%CI: 1.29-6.43) in Q2, 2.92 (95%CI: 1.44-6.57) in Q3 and 3.08 (95%CI: 1.11-6.69) in Q4, after multivariable-adjusted analyses. CONCLUSION: Increased triglycerides and high levels of total cholesterol and low-density lipoprotein were independently associated with an increased likelihood of estimated glomerular filtration rate (eGFR) decline and development of incident chronic kidney disease in the general Zhejiang population.


Asunto(s)
Dislipidemias/epidemiología , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/epidemiología , Adulto , Anciano , China/epidemiología , Colesterol/sangre , Dislipidemias/sangre , Femenino , Humanos , Hipertensión/epidemiología , Incidencia , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Estudios Retrospectivos , Triglicéridos/sangre , Adulto Joven
3.
Nephrology (Carlton) ; 25(9): 723-729, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31999031

RESUMEN

AIM: Evaluate the relationship between anti-Xa activity and anticoagulant effect, and ascertain whether accumulation of low-molecular-weight heparins (LMWH) occurs during haemodialysis. METHODS: There was an observational, single-centre study among participants who received the LMWH dalteparin, enoxaparin or nadroparin. A standard haemodialysis session lasted 4 hours. All included participants had anti-Xa activity measures at 0.5 and 4 hours. Extracorporeal circuit (ECC) clotting was evaluated by visual inspection of the haemodialyser and bubble trap after each haemodialysis session. The same person was tested at three consecutive haemodialysis sessions. RESULTS: Overall, 90 participants were enrolled and 259 haemodialysis sessions assessed. There was no significant difference in the mean anti-Xa activity at 0.5 and 4 hours for three consecutive sessions, so LMWH accumulation did not occur. There were 69 (26.6%) sessions in which, ECC clotting was visible. Compared with the group where circuit clotting did not occur, the LMWH dose and anti-Xa activity in the group where circuit clotting occurred were significantly lower. At 0.5 hour, anti-Xa <0.88 IU/mL had significantly higher odds of ECC clotting than that at ≥0.88 IU/mL. At 4 hours, anti-Xa <0.35 IU/mL had significantly higher odds of ECC clotting than that at ≥0.35 IU/mL. CONCLUSION: We found that over three haemodialysis sessions, no significant accumulation of LMWH was evident in subjects receiving a LMWH dose of between 2000 and 5000 IU for regular. Anti-Xa activity measurement can be used to adjust the dosage of LMWH and predict the anticoagulant effect during haemodialysis.


Asunto(s)
Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Deficiencia del Factor X , Heparina de Bajo-Peso-Molecular/farmacología , Fallo Renal Crónico , Diálisis Renal , China/epidemiología , Cálculo de Dosificación de Drogas , Deficiencia del Factor X/inducido químicamente , Deficiencia del Factor X/diagnóstico , Factor Xa/metabolismo , Femenino , Heparina de Bajo-Peso-Molecular/clasificación , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Diálisis Renal/efectos adversos , Diálisis Renal/métodos
4.
Sci Rep ; 10(1): 1240, 2020 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-31988377

RESUMEN

Facing on the complex electromagnetic environment of electrical equipment, based on the bio-anti-interference characteristics of neuron system, the bio-inspired electromagnetic protection is proposed in order to improve and assist the traditional electromagnetic protection method. In order to analyze the dynamical characteristics of electrical signal transfer process of neuron system, Hodgkin-Huxley (HH) model is adopted to calculate the action potential of single neuron. The initial value problem used in the parameters of Hodgkin-Huxley model is studied in order to satisfy the physiological phenomenon. The stability of HH model is analyzed to assess the dynamic stable performance of neuron. Based on the investigation of single neuron, a simple neuron system consisted of two neurons and one synapse is studied. The compassion between the action potential of posterior neuron and different synapse is performed, which explores how the mathematic models of different synapses influence the action potential. The relationship between action potential of posterior neuron and coupling strength of simplified synapse is calculated to explain the diversity of electrical signal output of neuron system. These numerical results enable to provide some datum for deeply developing the bio-inspired electromagnetic protection and well designing the bio-inspired circuit.


Asunto(s)
Sinapsis Eléctricas/fisiología , Campos Electromagnéticos/efectos adversos , Potenciales de Acción , Simulación por Computador , Radiación Electromagnética , Modelos Neurológicos , Modelos Estadísticos , Red Nerviosa/fisiología , Neuronas/fisiología , Potenciales Sinápticos/fisiología
5.
Cell Biol Int ; 44(2): 593-602, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31670413

RESUMEN

Derlin-1 is involved in the elimination of misfolded proteins and has been implicated in the progression of human cancers. However, its prognostic value and biological function in breast cancer remain unknown. Here, we show that Derlin-1 is overexpressed in breast cancer and exhibits oncogenic activities via interaction with UBE2C. Increased expression of Derlin-1 is correlated with lymph node metastasis, advanced clinical stage, and unfavorable overall survival in two cohorts containing over 1,000 patients. Multivariate analyses by the Cox regression model suggest Derlin-1 is an independent factor for poor prognosis. In vitro experiments demonstrate that Derlin-1 expression is transcriptionally upregulated by c-Myc. Ectopic expression of Derlin-1 promotes breast cancer cell proliferation and migration, whereas the knockdown of Derlin-1 results in the opposite phenotypes. Mechanistically, Derlin-1 directly binds to UBE2C to increase the phosphorylation of AKT and ERK. The treatment of UBE2C siRNA markedly attenuates Derlin-1-mediated cell growth and migration. Collectively, our data suggest Derlin-1 is a potential prognostic factor and functions as an oncogene in breast cancer.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Enzimas Ubiquitina-Conjugadoras/metabolismo , Apoptosis , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Movimiento Celular , Femenino , Humanos , Proteínas de la Membrana/genética , Fosforilación , Pronóstico , Transducción de Señal , Células Tumorales Cultivadas , Enzimas Ubiquitina-Conjugadoras/genética
6.
Oncol Lett ; 18(3): 3072-3080, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31452784

RESUMEN

Malignant peripheral nerve sheath tumors (MPNSTs) are unusual and aggressive malignant soft-tissue tumors that comprise 5-10% of all soft-tissue sarcomas. Approximately 50% of MPNST cases are associated with neurofibromatosis type-1 (NF-1). As a rare MPNST subset, the epithelioid variant of MPNST (eMPNST) is histologically characterized by the predominant presence of epithelioid tumor cells, and accounts for <5% of all MPNSTs. In addition, eMPNST is rarely associated with NF-1 when compared with conventional MPNST. Although extensive clinicopathological studies have been conducted on eMPNST, clinicians face difficulty when attempting to make an accurate diagnosis. Subsequently, the biological consequences, including recurrence, metastasis and mortality rate in patients with eMPNST remain unclear. The current study presents the case of a 71-year-old woman with eMPNST and a family history of NF-1 in whom tumors had recurred twice on the lower back. A literature search for eMPNSTs was conducted by browsing PubMed and MEDLINE for English-language articles, as well as references from review articles, and revealed 129 published cases. Only 5 cases of eMPNST were associated with NF-1. The studies were retrospectively reviewed and the clinicopathological data of the patients, including tumor site, treatment, follow-up, prognosis, and immunohistochemical positivity were collected.

7.
Histol Histopathol ; 34(6): 671-682, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30475382

RESUMEN

BACKGROUND: Diabetic nephropathy (DN) is a serious complication in diabetic patients and has been considered as the main cause of end-stage renal disease. However, there are no studies on the role of stromal interaction molecule (STIM) and its two subtypes, STIM1 and STIM2, in the epithelial-to-mesenchymal transition (EMT) of podocytes induced by diabetic kidney disease (DKD). The present study suggests for the first time that STIM inhibition decreases DKD-induced EMT. METHODS: All DKD patients were diagnosed based on renal biopsies carried out at the Department of Nephrology, Zhejiang Provincial People's Hospital and selected using the Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN. Images were taken and the number of positive puncta in cells was analyzed using software equipped for immunofluorescence microscopy. STIM1, STIM2, FcγRIIa, FcγRIIb, Nephrin, CTGF, and α-SMA protein levels were detected by Western blotting analysis using the corresponding antibodies. The viability of cells was measured using CCK-8 assays. Absorbance at 450 nm was measured with a Multiskan FC Microplate Reader (Thermo Scientific, USA) and the results were normalized to those of untreated cells. All statistical analyses were performed using SPSS 19.0 software (Stanford University, Stanford, CA, USA). RESULTS: A total of 30 DKD patients and 30 control patients were enrolled in the study. We found that the level of urine protein in patients and db/db diabetic mice is higher than control group and the levels of STIM1 and 2 significantly increased in DKD groups. We also demonstrated that STIM is upregulated during DKD injury. Next, we discovered that DKD-induced podocyte EMT is related to STIM overexpression in vivo and in vitro. Further research demonstrated that STIM siRNA reverses podocytes from DKD-induced injury and EMT and reverses FcγRII activity in HG-treated podocytes. CONCLUSION: Our study suggests that STIM and FcγRII play an essential role in the regulation of DKD-induced podocyte EMT. STIM is an essential component of FcγR activation and inhibition of STIM-mediated signaling pathway might be a new strategy to treat IgG-dependent renal diseases.


Asunto(s)
Nefropatías Diabéticas/metabolismo , Transición Epitelial-Mesenquimal , Proteínas de Neoplasias/metabolismo , Podocitos/metabolismo , Receptores de IgG/metabolismo , Molécula de Interacción Estromal 1/metabolismo , Molécula de Interacción Estromal 2/metabolismo , Anciano , Animales , Biopsia , Estudios de Casos y Controles , Supervivencia Celular , Diabetes Mellitus Experimental/patología , Femenino , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , ARN Interferente Pequeño/metabolismo , Regulación hacia Arriba
8.
BMC Nephrol ; 19(1): 190, 2018 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-30064367

RESUMEN

BACKGROUND: Investigations on the role of the time-mean serum uric acid (SUA) value in determining the risk of chronic kidney disease (CKD) are limited. We investigated whether the time-mean SUA value indicates the risk of CKD, and explored associations of the baseline and time-mean SUA levels with kidney function decline and incident CKD in a healthy population. METHODS: We initiated an inhabitant-based cohort study between January 2011 and December 2016. All participants completed a yearly medical check-up at the Zhejiang Province People's Hospital and had baseline estimated glomerular filtration rates (eGFR) > 60 ml/min/1.73m2. The SUA level and eGFR were assessed every year in the follow-up period. A multivariate adjusted binary logistic regression analysis and Cox proportional hazards models were used to evaluate the risk of newly-developed CKD among different stratified groups. RESULTS: During the 6-year follow-up period, 227 (4.4%) participants developed CKD. In multivariable-adjusted analyses, the odds ratio (OR) for new-onset CKD increased, with higher time-mean SUA levels than at baseline (OR: 1.00 [reference], 2.709 [95% confidence interval: 1.836-5.293], 3.754 [1.898-7.428], and 7.462 [3.694-15.073]). After adjustment for potential cofounders, a multivariate Cox proportional hazard model showed that a higher SUA increased the risk of developing CKD (the adjusted hazard ratios of the highest and lowest quartiles for the baseline and time-mean SUA levels were 1.689 [1.058-2.696] and 6.320 [3.285-12.159], respectively). CONCLUSION: An increased time-mean and single SUA value were independently associated with an increased likelihood of eGFR decline and development of new-onset CKD in the general population.


Asunto(s)
Vigilancia de la Población , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Ácido Úrico/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Insuficiencia Renal Crónica/diagnóstico , Estudios Retrospectivos , Factores de Tiempo
9.
Cell Physiol Biochem ; 48(2): 765-772, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30025409

RESUMEN

BACKGROUND/AIMS: The purpose of this study was to investigate the impact of rapamycin (RAP) on autophagy in podocytes and the therapeutic effects of RAP on idiopathic membranous nephropathy (IMN). METHODS: We established an in vitro model of IMN by preconditioning mouse podocytes with puromycin aminonucleoside (PAN). A Cell Counting Kit-8 was used to detect the proliferation of each group of podocytes. Podocyte apoptosis was analyzed by flow cytometry via annexin V/propidium iodide dual staining. Subsequently, we observed the number of autophagosomes by transmission electron microscopy. Western blotting was used to detect the levels of LC3, mTOR, p-mTOR, 4EBP1, p-4EBP1, P70S6K, and p-P70S6K in each group. RESULTS: The number of podocytes in the PAN + 100 ng/mL RAP group, PAN + 200 ng/mL RAP group, and PAN + 300 ng/mL RAP group was significantly increased (P < 0.01). The apoptotic rate of podocytes was significantly different between the PAN group and the PAN + RAP group (P < 0.001). There were fewer autophagic corpuscles in the PAN group and more autophagosomes were observed in the PAN + RAP group. LC3 protein expression was down-regulated in the PAN group, while its expression was up-regulated in the PAN + RAP group. In the PAN group, the levels of phosphorylated mTOR, 4EBP1, and P70S6K were increased, while in the PAN + RAP group, protein phosphorylation was reduced. CONCLUSIONS: RAP can effectively inhibit the mTOR/P70S6K/4EBP1 signaling pathway, and activate podocyte autophagy, consequently reducing podocyte apoptosis. Therefore, RAP could be used for the treatment of idiopathic membranous nephropathy.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Proteínas Adaptadoras Transductoras de Señales , Animales , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular , Línea Celular , Proliferación Celular/efectos de los fármacos , Factores Eucarióticos de Iniciación , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Fosfoproteínas/metabolismo , Podocitos/citología , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Puromicina Aminonucleósido/farmacología , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo
10.
Histol Histopathol ; 33(8): 803-814, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29446059

RESUMEN

BACKGROUND: Lupus nephritis (LN) is one of the most common and severe complications in Systemic lupus erythematosus patients, and the mechanism underlining the pathogenesis of LN is still unknown. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In this study, we investigated the role of autophagy in the progression of LN. METHODS: Autophagic activities in podocytes of both LN patients (Class IV and V) and mice were evaluated. Podocytes were observed by electron microscopy, and autophagic activity was evaluated by immunofluorescence staining and western blot analysis. Apoptotic activity was evaluated by immunohistochemistry, TUNEL assays and flow cytometric analysis. RESULTS: Significantly greater podocyte injury and discrepant autophagic levels were observed in LN patients. Differentiated mouse podocytes in the LN group showed reduced nephrin expression and increased apoptosis, as well as significantly higher levels of apoptosis-related proteins (cleaved caspase-3 and Bax). In the mice LN group, the increased number of autophagosomes was accompanied by increased LC3-II/LC3-I ratios and decreased p62, suggesting increased autophagic and apoptotic activity in podocytes. Blockade of autophagic activity by 3-MA or siRNA-mediated silencing of Atg5 resulted in decreases in LC3-II/LC3-I ratios, podocyte apoptosis and damage in the mice LN group. Futhermore, Rapamycin treatment increased LC3-II/LC3-I ratios, and enhanced LN-induced apoptosis in podocyte from modal animal. CONCLUSIONS: This study demonstrates that autophagic activity of podocytes is a crucial factor in renal injury by directly affecting the function of podocyte; thus, inhibiting this activity during the early stages of LN is implicated as a potential therapeutic strategy for delaying the progression of LN. Also, clinical application in LN needs to consider patients' pathological type and drugs' comprehensive effectiveness.


Asunto(s)
Autofagia , Nefritis Lúpica/patología , Podocitos/ultraestructura , Adenina/análogos & derivados , Adenina/farmacología , Adolescente , Adulto , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia/efectos de los fármacos , Proteínas Relacionadas con la Autofagia/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Humanos , Nefritis Lúpica/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos MRL lpr , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Sirolimus/farmacología , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...