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1.
J Formos Med Assoc ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38906733

RESUMEN

BACKGROUND PURPOSE: Rituximab (RTX),an anti-CD20 monoclonal antibody can effectively treat minimal change disease (MCD),with low toxicity and a reduced steroid dosage. The optimal dosage of RTX for treating MCD remains unclear. This study aimed to investigate the efficacy of an ultra-low-dose regimen of RTX (100 mg per week for 4 weeks) for treating MCD. METHODS: We retrospectively analyzed clinical data from 31 patients with MCD who received RTX. Seventeen patients received ultra-low-dose RTX (ULD-RTX) therapy, and 14 patients received standard-dose RTX (SD-RTX) therapy (500 mg weekly for 4 weeks). All patients were followed up for at least 6 months. RESULTS: Both groups showed significant increases in the serum albumin levels and notable decreases in the urinary protein levels in the 1st and 6th months after RTX therapy. There were no significant differences in the plasma albumin or urinary protein levels between the groups (p > 0.05). B-cell depletion was observed in all patients after 1 month of RTX administration. At 6 months after RTX treatment, the remission rate was 93% in the SD-RTX group and 88% in the ULD-RTX group (p > 0.05). The ULD-RTX therapy incurred lower costs than did the SD-RTX therapy. One patient in the SD-RTX group developed community-acquired pneumonia. CONCLUSION: Ultra-low-dose RTX is effective at inducing remission in patients with MCD at a lower cost.

2.
Am J Physiol Renal Physiol ; 322(6): F611-F624, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35403451

RESUMEN

Promoting adaptive repair in acute kidney injury (AKI) is an effective strategy to prevent the progression from AKI to chronic kidney disease. However, the mechanisms involved in renal repair after AKI remain unclear. In this study, we investigated the role of hypoxia-inducible factor (HIF), an important regulator of ischemic and hypoxic injury, in AKI during the repair phase. We established mouse models of ischemia-reperfusion injury-induced AKI with adaptive repair or maladaptive repair. We found that after injury, activation of HIF in the adaptive repair group was rapid, whereas in the maladaptive repair group HIF activation was relatively delayed, and its expression was significantly lower than that in the adaptive repair group during the early repair phase. To further investigate the mechanism of HIF, we regulated the expression of HIF-1α and HIF-2α in HK-2 cells and EA.hy926 cells, respectively. Silencing HIF expression reduced proliferation and increased apoptosis in cells injured by hypoxia/reoxygenation. Self-healing ability was further reduced due to the downregulation of HIF. Moreover, HIF overexpression had the opposite effect. HIF increased the expression of ß-catenin and its downstream target genes. Activation of Wnt/ß-catenin by the small-molecule activator SKL2001 mitigated the damaging effect of HIF knockdown, whereas blockade of ß-catenin with the inhibitor IWR-1-endo reduced the protective effects of HIF. In conclusion, HIF, which is highly expressed in the early stage after AKI, promotes renal repair by interacting with the Wnt/ß-catenin signaling pathway.NEW & NOTEWORTHY We investigated the role of hypoxia-inducible factor (HIF) in acute kidney injury in vivo and in vitro. Expression of HIF in the adaptive repair group was more rapid and sufficient than that in the maladaptive repair group during the early repair phase. HK-2 and EA.hy926 cells treated with hypoxia/reoxygenation were used to elucidate the cross talk between HIF and the Wnt/ß-catenin signaling pathway by which HIF played a renoprotective role in acute kidney injury.


Asunto(s)
Lesión Renal Aguda , Daño por Reperfusión , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/prevención & control , Animales , Humanos , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Ratones , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Vía de Señalización Wnt , beta Catenina/metabolismo
3.
4.
J Formos Med Assoc ; 121(11): 2288-2299, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35871036

RESUMEN

BACKGROUND/PURPOSE: The effect of roxadustat on iron homeostasis in patients with chronic kidney disease (CKD) is unclear. This study aimed to evaluate the efficacy of roxadustat for the treatment of iron metabolism disorders in dialysis-dependent (DD) and non-dialysis-dependent (NDD) CKD patients. METHODS: We searched the PubMed, Embase, China National Knowledge Internet and Web of Science databases for randomized controlled trials (RCTs). The primary outcomes were changes in serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT), ferritin, transferrin, and hepcidin. The secondary outcomes included the changes in hemoglobin (Hb) and the incidences of adverse events (AEs) and severe adverse events (SAEs). RESULTS: Twelve RCTs comprising 4976 participants were included. Compared to the control group, increases in the serum iron (SMD = 0.21, 95% CI: 0.15 to 0.27, P < 0.00001), TIBC (SMD = 1.02, 95% CI: 0.82 to 1.22, P < 0.00001) and transferrin levels (WMD = 0.55, 95% CI: 0.41 to 0.69, P < 0.00001) were found in the roxadustat group. Compared to the control group, decreases in the ferritin levels (WMD = -37.82, 95% CI: -59.89 to -15.74, P = 0.0008) and hepcidin levels (WMD = -24.04, 95% CI: -36.28 to -11.79, P = 0.0001) were observed in the roxadustat group. The meta-analysis showed that roxadustat significantly increases Hb levels (WMD = 0.77, 95% CI: 0.42 to 1.12, P < 0.0001). The incidences of AEs and SAEs in the roxadustat group was significantly higher than that in the control group (RR = 1.03, 95% CI: 1.00 to 1.07, P = 0.04; RR = 1.08, 95% CI: 1.00 to 1.15, P = 0.04). CONCLUSION: Our findings suggest that roxadustat could effectively improve iron metabolism in patients with CKD.


Asunto(s)
Anemia , Insuficiencia Renal Crónica , Anemia/etiología , Ferritinas , Glicina/análogos & derivados , Hemoglobinas/análisis , Hepcidinas/metabolismo , Humanos , Hierro , Isoquinolinas , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Transferrinas
5.
Physiol Plant ; 170(3): 318-334, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32754906

RESUMEN

Weeping is a specific plant architecture with high ornamental value. Despite the considerable importance of the weeping habit to landscaping applications and knowledge of plant architecture biology, little is known regarding the underlying molecular mechanisms. In this study, growth and phytohormone content were analyzed among the progeny of different branch types in an F1 mapping population of Prunus mume with varying plant architecture. Bulked segregant RNA sequencing was conducted to compare differences among progeny at a transcriptional level. The weeping habit appears to be a complex process regulated by a series of metabolic pathways, with photosynthesis and flavonoid biosynthesis highly enriched in differentially expressed genes between weeping and upright progeny. Based on functional annotation and homologous analyses, we identified 30 candidate genes related to weeping that merit further analysis, including 10 genes related to IAA and GA3 biosynthesis, together with 6 genes related to secondary branch growth. The results of this study will facilitate further studies of the molecular mechanisms underlying the weeping habit in P. mume.


Asunto(s)
Prunus , Secuencia de Bases , Prunus/genética , Transcriptoma/genética
6.
J Stroke Cerebrovasc Dis ; 29(10): 105109, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32912537

RESUMEN

OBJECTIVE: Homocysteine plays critical roles in cellular redox homeostasis, and hyperhomocysteinemia has been associated with multiple diseases, including neurological disorders involving reactive oxygen species-inducing and pro-inflammatory effects of homocysteine that are related to mitochondria. This study investigated the role of homocysteine in regulating mitochondria of neuron cell lines. METHODS: Neuron cells were pre-treated with homocysteine, and then flow cytometry was used to detect reactive oxygen species production and mitochondrial membrane potential, while Seahorse XFp Mito stress assay was used to comprehensively analyze mitochondrial function. RESULTS: The experimental results showed that high-concentration homocysteine diminished carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone-stimulated oxygen consumption rate and mitochondrial spare respiration capacity in a time- and concentration-dependent manner, and homocysteine also reduced reactive oxygen species in cultured neuron cell lines while no changes in mitochondrial membrane potential were observed. CONCLUSION: These results indicate that homocysteine diminished mitochondrial respiration function in neuron cell lines mediated by its reactive oxygen species-reducing effects, which may underlie the association between hyperhomocysteinemia and human diseases.


Asunto(s)
Homocisteína/toxicidad , Mitocondrias/efectos de los fármacos , Neuronas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Animales , Línea Celular , Respiración de la Célula/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ratones , Mitocondrias/metabolismo , Mitocondrias/patología , Neuronas/metabolismo , Neuronas/patología , Ratas , Factores de Tiempo
7.
J Tradit Chin Med ; 43(5): 897-905, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37679977

RESUMEN

OBJECTIVES: To investigate the anticancer effect of Pingxiao capsule (, PXC) on the treatment of breast cancer and . METHODS: The inhibition of PXC on cell viability and proliferation was determined by cell counting kit-8, EdU assay and colony formation assay, respectively. The effect of PXC on cell apoptosis was detected by using flow cytometry. The suppression of PXC on cell migration and invasion was investigated by chamber assay. To investigate the underlying molecular mechanisms, the expression of proteins related to epithelial to mesenchymal transition (EMT) was analyzed by Western blotting in breast cancer cells and by immunohistochemistry in tumor tissues. The anticancer effect of PXC was evaluated by using MDA-MB-231 xenograft model and 4T1 metastatic breast cancer model. RESULTS: Our results indicated that triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and MDA-MB-468 were sensitive to PXC. PXC potently inhibited the proliferation, colony formation, migration, and invasion of MDA-MB-231 and MDA-MB-468 cells . Then, MDA-MB-231 xenograft model depicted that PXC significantly reduced tumor size and weight compared with Control. 4T1 lung metastasis model showed that PXC significantly inhibited breast cancer cell spreading to lungs in mice. Mechanistically, PXC inhibited EMT process by reducing cadherin turnover in TNBC. Furthermore, PXC in combination with 8 Gy X-ray treatment obviously promoted the induction of apoptosis, and suppressed cell proliferation. CONCLUSION: PXC could inhibit the proliferation and invasion of TNBC both and , and exerted its anti-metastatic effect by regulating cadherin turnover, Furthermore, it sensitized the TNBC cells to radiotherapy. The data supported further development of PXC as an adjuvant-therapy agent for TNBC.


Asunto(s)
Neoplasias Pulmonares , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/radioterapia , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Apoptosis , Cadherinas/genética , Modelos Animales de Enfermedad
8.
Mol Genet Genomic Med ; 9(8): e1728, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34156167

RESUMEN

BACKGROUND: Pyruvate dehydrogenase complex (PDHC) deficiency is a common neurodegenerative disease associated with abnormal mitochondrial energy metabolism. The diagnosis of PDHC is difficult because of the lack of a rapid, accurate, and cost-effective clinical diagnostic method. METHODS: A 4-year-old boy was preliminarily diagnosed with putative Leigh syndrome based on the clinical presentation. PDHC activity in peripheral blood leukocytes and a corresponding gene analysis were subsequently undertaken. Sodium pyruvate 1-13 C was used for the analysis of PDHC activity in peripheral leukocytes. The genes encoding PDHC were then scanned for mutations. RESULTS: The results showed that the corresponding PDHC activity was dramatically decreased to 10.5 nmol/h/mg protein as compared with that of healthy controls (124.6 ± 7.1 nmol/h/mg). The ratio of PDHC to citrate synthase was 2.1% (control: 425.3 ± 27.1). The mutation analysis led to the identification of a missense mutation, NM_000284.4:g214C>T, in exon 3 of PDHC. CONCLUSION: The peripheral blood leukocyte PDHC activity assay may provide a practical enzymatic diagnostic method for PDHC-related mitochondrial diseases.


Asunto(s)
Pruebas Enzimáticas Clínicas/métodos , Leucocitos/metabolismo , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/diagnóstico , Complejo Piruvato Deshidrogenasa/metabolismo , Preescolar , Pruebas Genéticas/métodos , Humanos , Masculino , Mutación Missense , Complejo Piruvato Deshidrogenasa/genética , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/genética , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/metabolismo
9.
Medicine (Baltimore) ; 99(12): e19467, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32195946

RESUMEN

BACKGROUND: The findings on the association between elevated plasma homocysteine levels and the risk of the trial of org 10172 in acute stroke treatment (TOAST) of ischemic stroke have been inconsistent in Chinese. So far, there is no meta-analysis about the association between Hcy and the TOAST subtypes of ischemic stroke in Chinese. This study; therefore, aimed to evaluate whether elevated homocysteine levels are associated with the TOAST subtypes of ischemic stroke using a meta-analysis. MATERIALS AND METHODS: A systematic search of electronic databases were conducted for studies reporting homocysteine levels in ischemic stroke and the TOAST of ischemic stroke to April 18, 2018. The data were extracted after the application of inclusion and exclusion criteria. All the data were analyzed using Stata software version 9.0 (Stata Corp LP, College Station, TX). The standardized mean difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables. RESULTS: Thirteen studies comprising 3114 participants (2243 patients and 871controls) met the eligibility criteria and were included in the meta-analysis. The meta-analysis revealed that the ischemic stroke group had significantly higher levels of homocysteine than controls (SMD = 1.15, 95% CI = 0.85-1.45, P < .05). The subgroup analyses suggested that the groups of patients with large-artery atherosclerosis, small-vessel occlusion, cardioembolism, stroke of other determined etiology and stroke of undetermined etiology had significantly higher levels of homocysteine compared to those in the control group (large-artery atherosclerosis: SMD = 2.12, 95% CI = 1.40-2.84, P < .05; small-vessel occlusion: SMD = 1.10, 95% CI = 0.72-1.48, P < .05; CE: SMD = 1.17, 95% CI = 0.64-1.71, P < .05; stroke of other determined etiology: SMD = 0.88, 95% CI = 0.53-1.24, P < .05; stroke of undetermined etiology: SMD = 1.50, 95% CI = 0.66-2.33, P < .05, respectively). CONCLUSION: This meta-analysis found that ischemic stroke patients and the TOAST of ischemic stroke patients in Chinese had significantly higher homocysteine levels than the controls, suggesting that serum homocysteine levels may be a risk factor for ischemic stroke and the TOAST subtypes of ischemic stroke in Chinese.


Asunto(s)
Isquemia Encefálica/metabolismo , Homocisteína/sangre , Accidente Cerebrovascular/metabolismo , Aterosclerosis/complicaciones , Aterosclerosis/patología , Isquemia Encefálica/epidemiología , Isquemia Encefálica/patología , China/epidemiología , Humanos , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/patología
10.
Surg Endosc ; 23(4): 813-7, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18649097

RESUMEN

OBJECTIVE: There has been great interest in natural orifice transluminal endoscopic surgery (NOTES) in recent years. We report another new approach--transumbilical endoscopic surgery (TUES)--which we have performed in 40 cases for liver cysts (3), bleeding ascites (1), chronic appendicitis (10), and gallbladder diseases (26). METHODS: Transumbilical endoscopic liver cyst fenestration, abdominal cavity exploration, appendectomy, and cholecystectomy were performed in a total of 40 patients. RESULTS: All the operations were completed successfully except one case of intraoperative bleeding in TUES cholecystectomy which was converted to routine laparoscopic surgery. The operating times for TUES cholecystectomy, appendectomy, and liver cyst fenestration were 30-150 min,15-40 min, and 30-90 min, respectively. No postoperative bleeding or bile leakage occurred in this group of patients. CONCLUSIONS: Transumbilical endoscopic surgery is feasible, and would be another option for scarless abdominal surgery. TUES cholecystectomy is technically challenging. Careful selection of patients is important in the initial period of this technique.


Asunto(s)
Apendicectomía/métodos , Colecistectomía/métodos , Laparoscopía/métodos , Adolescente , Adulto , Anciano , Apendicitis/cirugía , Femenino , Estudios de Seguimiento , Enfermedades de la Vesícula Biliar/cirugía , Humanos , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Ombligo , Adulto Joven
11.
Surg Endosc ; 23(8): 1781-4, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19067062

RESUMEN

OBJECTIVE: The major barrier to transumbilical endoscopic surgery is external interference between the instrument handles around the umbilicus. We describe technique of totally transumbilical endoscopic cholecystectomy using improved instruments. METHODS: New trocars (5 and 3 mm in diameter, respectively) without proximal seal system on the sleeves were designed for this procedure. The maximum diameters of the trocars were reduced to 8 and 5 mm, respectively. The instruments used in this study were 5 cm longer than commercially available instruments. Ten cases of totally transumbilical cholecystectomy were performed successfully. RESULTS: All the gallbladders were removed successfully without severe bleeding during dissection, except one case of gallbladder wall perforation by cautery. Mean operating time was 62 +/- 25 min (range 45-110 min). All patients were satisfied with abdominal cosmetic results, discharged 48 h after the operation, and returned to work within seven postoperative days. CONCLUSIONS: External interference between trocars and instruments can be partially avoided by using the improved instruments. Totally transumbilical endoscopic cholecystectomy becomes feasible with this technique.


Asunto(s)
Colecistectomía Laparoscópica/métodos , Instrumentos Quirúrgicos , Adulto , Colelitiasis/cirugía , Cicatriz/prevención & control , Diseño de Equipo , Femenino , Enfermedades de la Vesícula Biliar/cirugía , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Pólipos/cirugía , Ombligo , Adulto Joven
12.
Artículo en Zh | WPRIM | ID: wpr-941011

RESUMEN

OBJECTIVE@#To propose an adaptive weighted CT metal artifact reduce algorithm that combines projection interpolation and physical correction.@*METHODS@#A normalized metal projection interpolation algorithm was used to obtain the initial corrected projection data. A metal physical correction model was then introduced to obtain the physically corrected projection data. To verify the effectiveness of the method, we conducted experiments using simulation data and clinical data. For the simulation data, the quantitative indicators PSNR and SSIM were used for evaluation, while for the clinical data, the resultant images were evaluated by imaging experts to compare the artifact-reducing performance of different methods.@*RESULTS@#For the simulation data, the proposed method improved the PSNR value by at least 0.2 dB and resulted in the highest SSIM value among the methods for comparison. The experiment with the clinical data showed that the imaging experts gave the highest scores of 3.616±0.338 (in a 5-point scale) to the images processed using the proposed method, which had significant better artifact-reducing performance than the other methods (P < 0.001).@*CONCLUSION@#The metal artifact reduction algorithm proposed herein can effectively reduce metal artifacts while preserving the tissue structure information and reducing the generation of new artifacts.


Asunto(s)
Algoritmos , Artefactos , Procesamiento de Imagen Asistido por Computador/métodos , Metales , Fantasmas de Imagen , Tomografía Computarizada por Rayos X/métodos
13.
Artículo en Zh | WPRIM | ID: wpr-941013

RESUMEN

OBJECTIVE@#To build a helical CT projection data restoration model at random low-dose levels.@*METHODS@#We used a noise estimation module to achieve noise estimation and obtained a low-dose projection noise variance map, which was used to guide projection data recovery by the projection data restoration module. A filtering back-projection algorithm (FBP) was finally used to reconstruct the images. The 3D wavelet group residual dense network (3DWGRDN) was adopted to build the network architecture of the noise estimation and projection data restoration module using asymmetric loss and total variational regularization. For validation of the model, 1/10 and 1/15 of normal dose helical CT images were restored using the proposed model and 3 other restoration models (IRLNet, REDCNN and MWResNet), and the results were visually and quantitatively compared.@*RESULTS@#Quantitative comparisons of the restored images showed that the proposed helical CT projection data restoration model increased the structural similarity index by 5.79% to 17.46% compared with the other restoration algorithms (P < 0.05). The image quality scores of the proposed method rated by clinical radiologists ranged from 7.19% to 17.38%, significantly higher than the other restoration algorithms (P < 0.05).@*CONCLUSION@#The proposed method can effectively suppress noises and reduce artifacts in the projection data at different low-dose levels while preserving the integrity of the edges and fine details of the reconstructed CT images.


Asunto(s)
Algoritmos , Artefactos , Tomografía Computarizada Espiral , Tomografía Computarizada por Rayos X/métodos
14.
Sci Rep ; 7: 45952, 2017 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-28383024

RESUMEN

Salt-sensitive hypertension (SSHT) leads to kidney interstitial fibrosis. However, the potential mechanisms leading to renal fibrosis have not been well investigated. In present study, Dahl salt-sensitive (DS) rats were divided into three groups: normal salt diet (DSN), high salt diet (DSH) and high salt diet treated with hydrochlorothiazide (HCTZ) (DSH + HCTZ). A significant increase in systolic blood pressure (SBP) was observed 3 weeks after initiating the high salt diet, and marked histological alterations were observed in DSH rats. DSH rats showed obvious podocyte injury, peritubular capillary (PTC) loss, macrophage infiltration, and changes in apoptosis and cell proliferation. Moreover, Wnt/ß-catenin signaling was significantly activated in DSH rats. However, HCTZ administration attenuated these changes with decreased SBP. In addition, increased renal and urinary Wnt4 expression was detected with time in DSH rats and was closely correlated with histopathological alterations. Furthermore, these alterations were also confirmed by clinical study. In conclusion, the present study provides novel insight into the mechanisms related to PTC loss, macrophage infiltration and Wnt/ß-catenin signaling in SSHT-induced renal injury and fibrosis. Therefore, multi-target therapeutic strategies may be the most effective in preventing these pathological processes. Moreover, urinary Wnt4 may be a noninvasive biomarker for monitoring renal injury after hypertension.


Asunto(s)
Hipertensión/complicaciones , Enfermedades Renales/patología , Riñón/patología , Animales , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Capilares/efectos de los fármacos , Capilares/metabolismo , Fibrosis/etiología , Hidroclorotiazida/farmacología , Hipertensión/fisiopatología , Hipertensión/prevención & control , Riñón/efectos de los fármacos , Riñón/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/prevención & control , Túbulos Renales/irrigación sanguínea , Túbulos Renales/metabolismo , Túbulos Renales/patología , Masculino , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Ratas Endogámicas Dahl , Cloruro de Sodio Dietético/administración & dosificación , Cloruro de Sodio Dietético/toxicidad , Proteína Wnt4/metabolismo , Proteína Wnt4/orina
15.
Chinese Pharmacological Bulletin ; (12): 1008-1015, 2021.
Artículo en Zh | WPRIM | ID: wpr-1014474

RESUMEN

Aim To explore the effect of endoplasmic reticulum (ER) stress-related exosomes derived from hepatocellular carcinoma (HCC) cells on the M2 polarization of macrophages via Toll-like receptor 4 (TLR4) and the underlying mechanism. Methods Western blot experiments were conducted to evaluate the GRP78 levels in HCC tissues and HCC cells with or without pre-treatment of tunicamycin and the identification of the isolated exosomes. Immunohistochemical staining was also employed to detect the expression of GRP78 in HCC tissues. Immunofluorescence was used to confirm the effective absorbance of exosomes by macrophages. Flow cytometry ( FCM ) , Western blot and CBA kit were used to detect M2 polarization-asso ciated markers and the expression of TLR4 on macrophages. Affymetrix gene chip and bioinformatics analy-sis were used to screen the differential expression of mRNA in macrophages stimulated by ER stressed-relat- ed exosomes and TLR4 expression. Results In clinical samples, GRP78 expression in liver cancer tissues was higher than that in the adjacent tissues. In cell experiments, tunicamycin (2.5 jxmol • L"1 ) treatment for 24 hours in HCC cells could significantly increase the expression of ER stress marker protein GRP78 compared with control group. Western blot showed that HCC cell-derived exosomes positively expressed exosom- al marker proteins,such as CD63,TSG101 and HSP70, and negatively expressed Calnexin. Interestingly, HSP70-enriched exosomes released by ER-stressed HCC cells were observed. Laser confocal microscopy found that exosomes could be effectively taken up by RAW264.7 macrophages. Flow cytometry and Western blot further indicated that ER stress-related exosomes could significantly up-regulate the expression of CD206, transformed growth factor-beta (TGF-p) and arginase-1 (Arg-1) in macrophages. Meanwhile, these exosomes could promote the secretion of IL-6 and IL- 10,and up-regulate the expression of TLR4 in macrophages. Conclusions ER stressed-HCC cells could promote macrophage M2 polarization by releasing HSP70-enriched exosomes and activating TLR4 signaling.

16.
Acta Physiologica Sinica ; (6): 855-862, 2021.
Artículo en Zh | WPRIM | ID: wpr-921289

RESUMEN

The present study was aimed to explore the correlation between θ-γ neural oscillations phase-amplitude coupling (PAC) in hippocampal CA3 area and the changes of spatial identifying and cognitive ability before and after shock avoidance training in rats. According to the results of Y-type maze shock avoidance training, the rats were divided into two groups: the fast avoidance response group and the general avoidance response group. The local field potential (LFP) of hippocampal CA3 area was recorded by wireless telemetry before and after shock avoidance training. The variation of θ oscillation (3-7 Hz) and low-γ neural oscillation (30-60 Hz) PAC in hippocampal CA3 area was analyzed by MATLAB wavelet packet extraction technique. The results showed that, compared with the general avoidance response group, the fast avoidance response group exhibited higher θ-γ neural oscillation PAC in hippocampal CA3 area before training. θ-γ oscillation PAC in hippocampal CA3 area was increased in both groups after training. It was also noticed that θ-γ neural oscillation PAC of some frequency bands in the general avoidance response group were significantly higher than those in the fast avoidance response group. The results suggest that certain intensity of training can change the spatial identifying and cognitive ability of rats, and the mechanism may involve the increase of the synchrony of θ-γ neural oscillation, i.e., the enhancement of θ-γ phase-amplitude alternating frequency coupling in hippocampal neurons.


Asunto(s)
Animales , Ratas , Cognición , Hipocampo , Neuronas , Ritmo Teta
17.
Front Plant Sci ; 6: 519, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26236320

RESUMEN

Carnation (Dianthus caryophyllus L.) is an important flower crop, having substantial commercial value as a cut-flower due to the long vase-life and wide array of flower colors and forms. Standard carnation varieties perform well under cool climates but are very susceptible to high temperatures which adversely affect the yield and the quality of the cut-flowers. Despite several studies of carnation contributing to the number of expressed sequence tags (ESTs), transcriptomic information of this species remains very limited, particularly regarding abiotic stress-related genes. Here, transcriptome analysis was performed to generate expression profiles of heat stress (HS)-responsive genes in carnation. We sequenced a cDNA library constructed with mixed RNA from carnation leaves subjected to 42°C HS (0, 0.5, 1, and 2 h) and 46°C HS (0.5, 1, and 2 h), and obtained 45,604,882 high quality paired-end reads. After de novo assembly and quantitative assessment 99,255 contigs were generated with an average length of 1053 bp. We then obtained functional annotations by aligning contigs with public protein databases including NR, SwissProt, KEGG, and COG. Using the above carnation transcriptome as the reference, we compared the effects of high temperature treatments (42°C: duration 0.5, 2, or 12 h) delivered to aseptic carnation seedlings, relative to untreated controls, using the FPKM metric. Overall, 11,471 genes were identified which showed a significant response to one or more of the three HS treatment times. In addition, based on GO and metabolic pathway enrichment analyses, a series of candidate genes involved in thermo-tolerance responses were selected and characterized. This study represents the first expression profiling analysis of D. caryophyllus under heat stress treatments. Numerous genes were found to be induced in response to HS, the study of which may advance our understanding of heat response of carnation.

18.
Artículo en Zh | WPRIM | ID: wpr-827972

RESUMEN

Fourteen compounds were isolated from the ethanol extract of Dalbergiae Odoriferae Lignum by various chromatographic techniques, including column chromatographies on silica gel, Sephadex LH-20 and semi-preparative HPLC. Their structures were determined by spectroscopic techniques as S-3'-hydroxy-7,2',4'-trimethoxyisoxane(1), 2-(2',4'-dimethoxyphenyl)-6-hydroxybenzofuran(2), 2-(2'-hydroxy-4'-methoxyphenyl)-6-methoxybenzofuran(3), 7,2',4'-trimethoxydihydroisoflavone(4), sativanone(5), 3,9-dimethoxy-6H-benzofuro[3,2-c]chromen-6-one(6),(6 aS,11 aS)-homopterocarpin(7),(6 aS,11 aS)-8-hydroxy-3,9-dimethoxypterocarpan(8),(6 aS,11 aS)-3,8,9-trimethoxypterocarpan(9), isodalbergin(10), isoliquiritigenin(11), butein(12), butin(13) and 3,7,4'-trihydroxyflavone(14). Among them, compound 1 was a new compound, while 2 and 3 were new natural products, 6, 8, 9 and 14 were isolated for the first time from Dalbergiae Odoriferae Lignum. Compounds 1-14 were tested for their cytotoxic activity against human hepatoma cell line BEL-7402, human gastric cancer cell line SCG-7901, human lung cancer cell line A549, human chronic myeloid leukemia cell line K562 and HeLa human cervical cancer cellline by MTT method. Compound 1 exhibited significant cytotoxicity with IC_(50) values ranging from 2.85 to 11.62 μg·mL~(-1). In addition, 2, 11 and 12 showed weak cytotoxic activities.


Asunto(s)
Humanos , Antineoplásicos , Cromatografía Líquida de Alta Presión , Células HeLa
19.
Artículo en Zh | MEDLINE | ID: mdl-15627708

RESUMEN

Carnation (Dianthus caryophyllus L.) is one of the most important cut flowers. The cultivar "Mabel" of carnation was transformed with direct repeat gene of ACC oxidase, the key enzyme in ethylene synthesis, driven by the CaMV35S promoter mediated by Agrobacterium tumefacien. Hygromycin phosphotransferase (HPT) gene was used as selection marker. Leaf explants were pre-cultured on shoot-inducing medium for 2 d, then immersed in Agrobacterium suspension for 8-12 min. Co-cultivation was carried out on the medium (MS+BA 1.0 mg/L+NAA 0.3 mg/L +Acetosyringone 100 micromol/L, pH 5.8-6.0) for 3 d. After that transformants were obtained by transferring explants to selection medium supplemented with 5 mg/L hygromycin (Hyg) and 400 mg/L cefotaxime (Cef). Southern blotting detection showed that a foreign gene was integrated into the carnation genome and 3 transgenic lines (T257, T299 and T273 line) obtained. Addition of acetosyringone and the time of co-culture were the main factors that influenced transformation frequency. After being transplanted to soil, transgenic plants were grew normally in greenhouse. Ethylene production of cut flower of transgenic T257 line was 95% lower than that of the control, and that of T299 line was reduced by 90% than that of the control, while that of transgenic T273 line has no of significantly different from control. Vase life of transgenic T257 line was 5 d longer than that of the control line at 25 degrees C.


Asunto(s)
Aminoácido Oxidorreductasas/genética , Dianthus/genética , Genoma de Planta , Dianthus/crecimiento & desarrollo , Etilenos/metabolismo , Plantas Modificadas Genéticamente , Transformación Genética
20.
Artículo en Zh | WPRIM | ID: wpr-805815

RESUMEN

Objective@#To evaluate the effect of Annexin-A1 mimetic peptide Ac2-26 on activation of astrocytes in rats.@*Methods@#The primarily cultured astrocytes from the cortex of fetal Sprague-Dawley rats after 4 passages were divined into 4 groups (n=24 each) using a random number table method: control group (C group), LPS group, LPS+ scramble peptide group (LPS+ Src group) and LPS+ Ac2-26 group.LPS was added to LPS group with the final concentration of 1 mg/ml.LPS at the final concentration of 1 mg/ml and scramble peptide at the final concentration of 3.3 mmol/L were added to LPS+ Src group.LPS at the final concentration of 1 mg/ml and Ac2-26 at the final concentration of 3.3 mmol/L were added to LPS+ Ac2-26 group.After 24-h incubation, the cell survival rate was measured by CCK-8 assay, the migration was determined by Transwell assay, the concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1a (MIP-1a) in the supernatant were measured (by enzyme-linked immunosorbent assay), and the expression of glial fibrillary acidic protein (GFAP), extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), p38 mitogen-activated protein kinase (p38MAPK), and phosphorylated p38MAPK (p-p38MAPK) in astrocytes was detected by Western blot.@*Results@#Compared with group C, the expression of GFAP was significantly up-regulated, and the cell mobility, concentrations of TNF-α, IL-1β, MCP-1 and MIP-1α in the supernatant, p-ERK/ERK ratio, p-JNK/JNK ratio and p-p38MAPK/p38MAPK ratio were increased (P<0.05), and no significant change was found in the cell survival rate in group LPS (P>0.05). Compared with group LPS, the expression of GFAP was significantly down-regulated, and the cell mobility, concentrations of TNF-α, IL-1β, MCP-1 and MIP-1α in the supernatant, p-JNK/JNK ratio and p-p38MAPK/p38MAPK ratio were decreased in group LPS+ Ac2-26 (P<0.05), and no significant change was found in the parameters mentioned above in group LPS+ Src (P>0.05).@*Conclusion@#Ac2-26 can inhibit activation of astrocytes and produces anti-inflammatory effect in rats.

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