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Apoptotic proteins play a crucial role in the apoptosis process, ensuring a balance between cell proliferation and death. Thus, further elucidating the regulatory mechanisms of apoptosis will enhance our understanding of their functions. However, the development of computational methods to accurately identify positive and negative regulation of apoptosis remains a significant challenge. This work proposes a machine learning model based on multi-feature fusion to effectively identify the roles of positive and negative regulation of apoptosis. Initially, we constructed a reliable benchmark dataset containing 200 positive regulation of apoptosis and 241 negative regulation of apoptosis proteins. Subsequently, we developed a classifier that combines the support vector machine (SVM) with pseudo composition of k-spaced amino acid pairs (PseCKSAAP), composition transition distribution (CTD), dipeptide deviation from expected mean (DDE), and PSSM-composition to identify these proteins. Analysis of variance (ANOVA) was employed to select optimized features that could yield the maximum prediction performance. Evaluating the proposed model on independent data revealed and achieved an accuracy of 0.781 with an AUROC of 0.837, demonstrating our model's potent capabilities.
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BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.
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Tasa de Filtración Glomerular , Glomerulonefritis por IGA , Proteinuria , Humanos , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/fisiopatología , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/terapia , Masculino , Femenino , Niño , Adulto , Proteinuria/etiología , Proteinuria/diagnóstico , Adolescente , Estudios Prospectivos , Adulto Joven , Pronóstico , Persona de Mediana Edad , Factores de Edad , Hematuria/etiología , Hematuria/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/diagnóstico , Riñón/patología , Riñón/fisiopatología , Progresión de la Enfermedad , Glucocorticoides/uso terapéuticoRESUMEN
Chinese college students have a high incidence of psychological problems but rarely seek professional psychological help. Despite this fact, there have been few studies of the help-seeking behavior of Chinese college students with mental health problems. This research aims to use a modified model based on the theory of planned behavior (TPB) to explore the intentions and behaviors of Chinese college students with psychological problems in seeking professional psychological help. A total of 319 Chinese college students were recruited to measure attitude, stigma, coping efficiency, help-seeking intention, help-seeking behavior, and demographic variables. The results showed that attitudes were the most powerful predictor of intentions to seek help, followed by coping effectiveness and stigma. In addition, a multigroup analysis showed that the model was valid across genders. Our research results show that the TPB-based model can effectively explain the intentions and behaviors of college students with psychological problems in seeking professional help. Using our results, families, schools, and society could design intervention measures to enhance students' help-seeking intentions and behaviors.
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Conducta de Búsqueda de Ayuda , Teoría del Comportamiento Planificado , Humanos , Masculino , Femenino , Actitud , Estudiantes/psicología , Intención , UniversidadesRESUMEN
Metabolic switch is critical for cell fate determination through metabolic functions, epigenetic modifications, and gene expression. However, the mechanisms underlying these alterations and their functional roles remain unclear. Here, we show that Plin2-mediated moderate lipid hydrolysis is critical for pluripotency of embryonic stem cells (ESCs). Upon exit from pluripotency, lipid droplet (LD)-associated protein Plin2 is recognized by Hsc70 and degraded via chaperone-mediated autophagy to facilitate LD mobilization. Enhancing lipid hydrolysis by Plin2 knockout promotes pluripotency exit, which is recovered by ATGL inhibition. Mechanistically, excessive lipid hydrolysis induces a dramatic lipidomic remodeling characterized by decreased cardiolipin and phosphatidylethanolamine, which triggers defects in mitochondrial cristae and fatty acid oxidation, resulting in reduced acetyl-CoA and histone acetylation. Our results reveal how LD mobilization is regulated and its critical role in ESC pluripotency, and indicate the mechanism linking LD homeostasis to mitochondrial remodeling and epigenetic regulation, which might shed light on development and diseases.
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Histonas , Gotas Lipídicas , Gotas Lipídicas/metabolismo , Acetilación , Histonas/metabolismo , Epigénesis Genética , Lipidómica , Perilipina-2/genética , Perilipina-2/metabolismo , LípidosRESUMEN
OBJECTIVES: The advanced non-small cell lung cancer (NSCLC) patients with pleural effusion have no opportunity for surgery treatment. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the first-line drugs for these patients with EGFR-sensitive mutation. However, the disease progression and drug update during or after treatment of EGFR-TKIs bring more challenges and puzzles to clinical diagnosis and treatment, which inevitably requires archived pleural cell samples for EGFR re-examination or comparative study. Understanding the DNA quality of archived pleural fluid samples and effectively using archival data of pleural fluid cells are of great significance for tracing the origin of cases and basic medical research. This study aims to evaluate the consistency of EGFR mutant gene expression between the 2 methods, and to explore a reliable way for preserving cytological data and making full use of cytological archival data via cell HE staining smear and cell paraffin section. METHODS: A total of 57 pleural fluid cytology cases in the Department of Pathology of China Aerospace Center Hospital from October 2014 to April 2021 were selected. Tumor cells were detected by cell HE staining smears and immunohistochemical staining for TTF-1 and Napsin A in the paired cell paraffin sections. There were more than 200 tumor cells in cell HE staining smear and the proportion of tumor cells were ≥70% in matched cell paraffin sections. Patients with 2 cell smears (one for cell data retention and the other for DNA extraction) were selected as the research subjects, and 57 pleural fluid samples were enrolled. EGFR gene mutation was detected by amplification refractory mutation system-polymerase chain reaction in 57 paired cell HE staining smears and cell paraffin sections. DNA concentration was 2 ng/µL. Cell HE smear was amplified side-by-side with DNA samples from paired cell paraffin sections. Result determination was according to the requirements of the reagent instructions. The external control cycle threshold (Ct) value of the No. 8 well of the samples to be tested was between 13 and 21, which was considered as successful and reliable samples. When the Ct value of EGFR gene mutation was <26, it was considered as positive; when the Ct value was between 26 and 29, it was critical positive; when the Ct value was equal or more than 29, it was negative. ΔCt value was the difference between mutant Ct value and externally controlled Ct value. The smaller the ΔCt value was, the better the quality of DNA of the detected sample was. RESULTS: Among the 57 pleural effusion samples, 42 patients were hospitalized with pleural effusion as the first symptom, accounting for 73.7% (42/57). EGFR mutation was detected in 37 samples [64.9% (37/57)]. The mutation rate for 19del was 37.8% (14/37) while for L858R was 48.6% (18/37). Females were 56.7% (21/37) of mutation cases. The mutation consistency rate of cell HE staining smear and matched cell paraffin sections was 100%. The ΔCt values of cell HE staining smears were less than those of matched cell paraffin sections. The mutation Ct values of 37 cytological samples were statistically analyzed according to the preservation periods of the years of 2014-2015, 2016-2017, 2018-2019, and 2020-2021. There were significant differences in cell paraffin section in the years of 2014-2015 and 2016-2017 compared with the years of 2018-2019 and 2020-2021, while no significant differences were found in cell HE staining smear. Statistical analysis of externally controlled Ct values of 57 cytological samples showed that there were significant differences between cell HE staining smears and cell paraffin section in the years of 2014-2015 and 2016-2017, compared with the years of 2018-2019 and 2020-2021. The mutational Ct values of 37 paired cell blocks and smears were all <26, and the externally controlled Ct values of 57 paired cell paraffin sections and HE staining smears were all between 13 and 21. CONCLUSIONS: The DNA quality of cell HE smears and matched cell paraffin section met the qualified requirements. Two methods possess show an excellent consistency in detecting EGFR mutation in NSCLC pleural fluid samples. The DNA quality of cell HE staining smear is better than that of cell paraffin sections, so cell HE staining smear can be used as important supplement of the gene test source. It should be noted that the limitation of cell HE staining smears is non-reproducibility, so multiple smears of pleural fluid are recommended to be prepared for multiple tests.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Derrame Pleural , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Análisis Mutacional de ADN/métodos , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Mutación , Parafina/uso terapéutico , Derrame Pleural/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Coloración y EtiquetadoRESUMEN
Somatic cell reprogramming is an ideal model for studying epigenetic regulation as it undergoes dramatic chromatin remodeling. However, a role for phosphorylation signaling in chromatin protein modifications for reprogramming remains unclear. Here, we identified mitogen-activated protein kinase kinase 6 (Mkk6) as a chromatin relaxer and found that it could significantly enhance reprogramming. The function of Mkk6 in heterochromatin loosening and reprogramming requires its kinase activity but does not depend on its best-known target, P38. We identified Gatad2b as a novel target of Mkk6 phosphorylation that acts downstream to elevate histone acetylation levels and loosen heterochromatin. As a result, Mkk6 over-expression facilitates binding of Sox2 and Klf4 to their targets and promotes pluripotency gene expression during reprogramming. Our studies not only reveal an Mkk phosphorylation mediated modulation of chromatin status in reprogramming, but also provide new rationales to further investigate and improve the cell fate determination processes.
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Cromatina , Heterocromatina , Reprogramación Celular , Epigénesis Genética , MAP Quinasa Quinasa 6/genética , MAP Quinasa Quinasa 6/metabolismo , FosforilaciónRESUMEN
OBJECTIVES: To study the effect of puromycin aminonucleoside (PAN) on the apoptosis of mouse podocyte clone 5 (MPC-5) and the expression of recombinant human Parkinson's disease 7 (Park7) and to study the protective mechanism of tacrolimus (FK506) against MPC-5 injury. METHODS: MPC-5 cells were cultured in vitro and then divided into three groups: blank control (control), PAN, and FK506. The cells in the PAN group were added with PAN (with a concentration of 50 mg/L) to establish a model of MPC-5 injury, and those in the FK506 group were added with PAN (with a concentration of 50 mg/L) and FK506 (with a concentration of 5 mg/L). An inverted microscope was used to observe the morphology and structure of MPC-5 cells at 12, 24, and 48 hours after treatment. Flow cytometry was used to measure cell apoptosis rate. Quantitative real-time PCR was used to measure the mRNA expression of Park7. Western blot and immunofluorescent staining were used to measure the protein expression of Park7. RESULTS: The control group had a large number of foot processes of the cell body at all time points, with tight connections between cells and a normal morphology. Compared with the control group, the PAN group had a significantly smaller cell volume at all time points, with loose connections between cells and the presence of ruptured cells. Compared with the PAN group, the FK506 group had an increased cell volume at all time points, with tighter connections between cells and a better morphology. The PAN group had a significantly higher apoptosis rate than the control group at all time points. Compared with the PAN group, the FK506 group had a significant reduction in the apoptosis rate at all time points (P<0.01). The PAN group had a significantly higher mRNA expression level of Park7 than the control group at all time points. Compared with the PAN group, the FK506 group had a significant reduction in the mRNA expression level of Park7 at all time points (P<0.01). Western blot showed that the PAN group had a significantly higher protein expression level of Park7 than the control group at all time points. Compared with the PAN group, the FK506 group had a significant reduction in the protein expression level of Park7 at all time points (P<0.01). Immunofluorescent staining showed that in the PAN group, there was a significantly lower expression of Park7 protein in cell membrane and cytoplasm, with a dense cluster distribution and increased fluorescence intensity. Compared with the PAN group, the FK506 group had a significant improvement in the distribution of Park7 protein. CONCLUSIONS: PAN can act on MPC-5 cells and cause morphological and structural damage and apoptosis of MPC-5 cells, as well as upregulated mRNA and protein expression of Park7. FK506 can downregulate the mRNA and protein expression of Park7 in the model of MPC-5 injury, maintain cellular homeostasis, reduce proteinuria, and delay glomerulosclerosis.
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Enfermedad de Parkinson , Podocitos , Animales , Ratones , Proteína Desglicasa DJ-1 , Puromicina Aminonucleósido/toxicidad , Tacrolimus/farmacologíaRESUMEN
OBJECTIVE: To investigate the mechanism through which tacrolimus, often used to treat refractory nephropathy, protects against puromycin-induced podocyte injury. METHODS: An in vitro model of puromycin-induced podocyte injury was established by dividing podocytes into three groups: controls, puromycin only (PAN group), and puromycin plus tacrolimus (FK506 group). Podocyte morphology, number, apoptosis rate and microtubule associated protein 1 light chain 3 alpha (LC3) expression were compared. RESULTS: Puromycin caused podocyte cell body shrinkage and loose intercellular connections, but podocyte morphology in the FK506 group was similar to controls. The apoptosis rate was lower in the FK506 group versus PAN group. The low level of LC3 mRNA observed in untreated podocytes was decreased by puromycin treatment; however, levels of LC3 mRNA were higher in the FK506 group versus PAN group. Although LC3-I and LC3-II protein levels were decreased by puromycin, levels in the FK506 group were higher than the PAN group. Fewer podocyte autophagosomes were observed in the control and FK506 groups versus the PAN group. Cytoplasmic LC3-related fluorescence intensity was stronger in control and FK506 podocytes versus the PAN group. CONCLUSIONS: Tacrolimus inhibited puromycin-induced mouse podocyte damage by regulating LC3 expression and enhancing autophagy.
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Podocitos , Animales , Apoptosis , Autofagia , Ratones , Puromicina/efectos adversos , Puromicina Aminonucleósido , TacrolimusRESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Somatic cell reprogramming provides insight into basic principles of cell fate determination, which remain poorly understood. Here we show that the transcription factor Glis1 induces multi-level epigenetic and metabolic remodelling in stem cells that facilitates the induction of pluripotency. We find that Glis1 enables reprogramming of senescent cells into pluripotent cells and improves genome stability. During early phases of reprogramming, Glis1 directly binds to and opens chromatin at glycolytic genes, whereas it closes chromatin at somatic genes to upregulate glycolysis. Subsequently, higher glycolytic flux enhances cellular acetyl-CoA and lactate levels, thereby enhancing acetylation (H3K27Ac) and lactylation (H3K18la) at so-called 'second-wave' and pluripotency gene loci, opening them up to facilitate cellular reprogramming. Our work highlights Glis1 as a powerful reprogramming factor, and reveals an epigenome-metabolome-epigenome signalling cascade that involves the glycolysis-driven coordination of histone acetylation and lactylation in the context of cell fate determination.
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Proteínas de Unión al ADN/metabolismo , Epigenoma , Células Madre Pluripotentes Inducidas , Metaboloma , Transducción de Señal/genética , Transducción de Señal/fisiología , Factores de Transcripción/metabolismo , Acetilcoenzima A/metabolismo , Animales , Reprogramación Celular , Senescencia Celular , Inmunoprecipitación de Cromatina , Glucosa/metabolismo , Ácido Láctico/metabolismo , Masculino , Ratones , Plásmidos/genéticaRESUMEN
The method for the determmation of trace boron, molybdenum, silver, tin and lead in geochemical samples by direct current are full spectrum direct reading atomic emission spectroscopy (DC-Arc-AES) was established. Direct current are full spectrum direct reading atomic emission spectrometer with a large area of solid-state detectors has functions of full spectrum direct reading and real-time background correction. The new electrodes and new buffer recipe were proposed in this paper, and have applied for national patent. Suitable analytical line pairs, back ground correcting points of elements and the internal standard method were selected, and Ge was used as internal standard. Multistage currents were selected in the research on current program, and each current set different holding time to ensure that each element has a good signal to noise ratio. Continuous rising current mode selected can effectively eliminate the splash of the sample. Argon as shielding gas can eliminate CN band generating and reduce spectral background, also plays a role in stabilizing the are, and argon flow 3.5 L x min(-1) was selected. Evaporation curve of each element was made, and it was concluded that the evaporation behavior of each element is consistent, and combined with the effects of different spectrographic times on the intensity and background, the spectrographic time of 35s was selected. In this paper, national standards substances were selected as a standard series, and the standard series includes different nature and different content of standard substances which meet the determination of trace boron, molybdenum, silver, tin and lead in geochemical samples. In the optimum experimental conditions, the detection limits for B, Mo, Ag, Sn and Pb are 1.1, 0.09, 0.01, 0.41, and 0.56 microg x g(-1) respectively, and the precisions (RSD, n=12) for B, Mo, Ag, Sn and Pb are 4.57%-7.63%, 5.14%-7.75%, 5.48%-12.30%, 3.97%-10.46%, and 4.26%-9.21% respectively. The analytical accuracy was validated by national standards and the results are in agreement with certified values. The method is simple, rapid, is an advanced analytical method for the determination of trace amounts of geochemical samples' boron, molybdenum, silver, tin and lead, and has a certain practicality.
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A method for the determination of high content of tin in geochemical samples by solid emission spectrometry was presented. The dedicated high content tin spectrum standard series was developed. K2S2O7, NaF, Al2O3 and carbon powder were used as buffers and Ge was used as internal standard, and the ratio of sample/matrix/buffer is 1 : 1 : 2. A weak sensitive line (Sn 242. 170 0 nm) was used as the analytical line. The technologies of vertical electrodes, AC arc overlap spectrograph, interception of the exposure, quantitative computer translation spectrum and background correction were used. The determination range is 100-22 350 microg x g(-1), the detection limit is 16.64 microg x g(-1), and the precision is (RSD, n = 12) 4.11%-6.46%. The accuracy of the method has been verified by determination of high content of tin in national geochemical standard samples and the results are in agreement with certified value. The method can be used for measurement directly without dilution of high content of tin in geochemical samples, and it greatly improved the detection upper limit for the determination of tin with solid emission spectroscopy and has certain practical value.
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OBJECTIVE: To identify the genes differentially expressed among the steroid-resistant nephrotic syndrome (SRNS), steroid-sensitive nephrotic syndrome (SSNS) and normal children, and understand the molecular mechanism of SRNS. METHODS: Affymetrix microarray technology was used to obtain such a profile. The differentially expressed genes among these groups were identified based on signal-to-noise ratios by GCOS software; real-time PCR analysis was performed to confirm the microarray results. RESULTS: There were 157 genes differentially expressed among these groups. The genes up-regulated both in SRNS and SSNS were involved primarily in ionic transportation, immuno-signal transduction and apoptosis. In particular, CLNS1A gene was down regulated in SRNS but up regulated in SSNS. CONCLUSION: Several differentially expressed genes, such as CLNS1A and HLA-DRB4 were found to be closely related to the pathogenesis of SRNS and SSNS. This DNA microarray analysis has provided some important clue to the molecular mechanism of SRNS.
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Regulación de la Expresión Génica/efectos de los fármacos , Síndrome Nefrótico/genética , Esteroides/uso terapéutico , Niño , Perfilación de la Expresión Génica , Humanos , Síndrome Nefrótico/tratamiento farmacológicoRESUMEN
PURPOSE: To explore the protective effect of glycyrrhizin in rats with nephrotic syndrome (NS) induced by adriamycin (ADR). METHODS: 36 Sprague Dawley (SD) male rats were divided into control, untreated and glycyrrhizin treatment groups. The NS rat model was established by injecting ADR twice in the untreated and in the glycyrrhizin treatment groups. Rats in the glycyrrhizin treatment group were fed glycyrrhizin by intragastric administration for 7 days. Changes in the following indices were observed in the three groups before and 4 weeks after the treatment: 24 h urine protein quantitation (UPr), serum cholesterol (Ch), serum albumin (Alb), blood urea nitrogen (BUN), serum creatinine (sCr), laminin (LN), fibronectin (FN), collagen (Col), transforming growth factor beta1 (TGFbeta1) and connective tissue growth factor (CTGF); histopathology by light and electron microscope. Expression of LN, FN, ColIV, TGFbeta1 and CTGF in the cortex of the kidney were detected by semi-quantitative immunohistochemical analysis. Expression of TGFbeta1 and CTGF in the cortex of the kidney was detected by Fluorescein Based Quantitive RT-PCR. Macrophage infiltration was evaluated by the immunoperoxidase staining. RESULTS: Compared with the control group, 24 h UPr, Ch, BUN and sCr of rats in the untreated group were increased. Glycyrrhizin reduced 24 h Upr, Ch, BUN, sCr, LN, FN, Col, TGFbeta1, CTGF, and mean arterial blood pressure. Pathological changes in the kidney, the expression of LN, FN, Col, TGFbeta1 and CTGF in the cortex of the kidney in the glycyrrhizin treatment group were decreased compared with the untreated group. Glycyrrhizin also suppressed macrophage infiltration in the kidneys of NS rat models. CONCLUSION: Glycyrrhizin exerts protective effects in rats with NS, reducing the excretion of Upr, Ch, BUN, sCr, and mean arterial blood pressure, and also decreasing expression of LN, FN, Col, TGFbeta1 and CTGF in the kidney. Renal function is improved and the severity of NS is lessened.
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Antiinflamatorios/uso terapéutico , Ácido Glicirrínico/uso terapéutico , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Antibióticos Antineoplásicos/toxicidad , Doxorrubicina/toxicidad , Ácido Glicirrínico/farmacología , Inmunohistoquímica , Corteza Renal/efectos de los fármacos , Corteza Renal/patología , Masculino , Síndrome Nefrótico/patología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Purpose: To explore the protective effect of glycyrrhizin in rats with nephrotic syndrome (NS) induced by adriamycin (ADR). Methods: 36 Sprague Dawley (SD) male rats were divided into control, untreated and glycyrrhizin treatment groups. The NS rat model was established by injecting ADR twice in the untreated and in the glycyrrhizin treatment groups. Rats in the glycyrrhizin treatment group were fed glycyrrhizin by intragastric administration for 7 days. Changes in the following indices were observed in the three groups before and 4 weeks after the treatment: 24h urine protein quantitation (UPr), serum cholesterol (Ch), serum albumin (Alb), blood urea nitrogen (BUN), serum creatinine (sCr), laminin (LN), fibronectin (FN), collagen (Col), transforming growth factor ?1 (TGF?1) and connective tissue growth factor (CTGF); histopathology by light and electron microscope. Expression of LN, FN, Col?, TGF?1 and CTGF in the cortex of the kidney were detected by semi-quantitive immunohistochemical analysis. Expression of TGF?1 and CTGF in the cortex of the kidney was detected by Fluorescein Based Quantitive RT-PCR. Macrophage infiltration was evaluated by the immunoperoxidase staining. Results: Compared with the control group, 24h UPr, Ch, BUN and sCr of rats in the untreated group were increased. Glycyrrhizin reduced 24h Upr, Ch, BUN, sCr, LN, FN, Col, TGF?1, CTGF, and mean arterial blood pressure. Pathological changes in the kidney, the expression of LN, FN, Col, TGF?1 and CTGF in the cortex of the kidney in the glycyrrhizin treatment group were decreased compared with the untreated group. Glycyrrhizin also suppressed macrophage infiltration in the kidneys of NS rat models. Conclusion: Glycyrrhizin exerts protective effects in rats with NS, reducing the excretion of Upr, Ch, BUN, sCr, and mean arterial blood pressure, and also decreasing expression of LN, FN, Col, TGF?1 and CTGF in the kidney. Renal function is improved and the severity of NS is lessened.
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OBJECTIVE: To observe the effects of fosinopril (FOS) on proliferation and secretion of extracellular matrix of rat glomerular mesangial cell induced by LPS. METHODS: In vitro culture method for glomerular mesangial cells (GMC) of rat was established and passages 3 - 10 of the cells were used in the experiment after identification. The experiment included the following 5 groups: control group (Ctrl), LPS group (LPS), high, medium and low dose FOS groups (FOS1, FOS2 and FOS3 groups, respectively). GMC proliferation was detected by methyl thiazolyl tetrazolium (MTT) incorporation method at 24 and 48 h; the changes of laminin (LN), fibronectin (FN) and ColIV protein secretion was detected by the enzyme-linked immunosorbent assay (ELISA). The changes of LNbeta(2) mRNA expression was detected by semi-quantitative real-time RT-PCR. RESULTS: (1) LPS could induce the mesangial cell proliferation, FOS inhibited this effect of proliferation induced by LPS. (2) Mesangial cells could secrete some extracellular matrix (ECM) protein in normal culture medium, mesangial cell secreted ECM protein was significantly higher in LPS group than that in Ctrl group (P < 0.01), but significantly lower in all FOS groups than that in LPS group (P < 0.01). (3) Mesangial cell could express LNbeta(2) mRNA in normal culture medium, LNbeta(2) mRNA expression was significantly higher in LPS group than that in Ctrl group at all time points, but was significantly lower in FOS group than that in LPS group. CONCLUSIONS: LPS could induce increased secretion of the ECM, including LN, FN, ColIV; FOS could inhibit the secretion of ECM in GMC in a dose-dependent manner at mRNA and protein levels.
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Proliferación Celular , Proteínas de la Matriz Extracelular/metabolismo , Fosinopril/farmacología , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Animales , Células Cultivadas , Regulación de la Expresión Génica , Lipopolisacáridos , RatasRESUMEN
OBJECTIVE: To explore the therapeutic effects of the extract of Ginkgo biloba leaf on hypercholestrolemia in children with primary nephritic syndrome (NS). METHODS: Thirty-five children with NS were randomized into 2 groups for treatment with prednisone plus Ginkgo biloba leaf extract (18 cases) or with prednisone plus dipyridamole (17 cases) for 8 weeks. After completion of the treatments, the therapeutic effects were evaluated and the changes in the blood biochemical markers assayed. RESULTS: The 8-week treatment with the extract significantly ameliorated the clinical symptoms and blood biochemistry as compared with prednisone plus dipyridamole group (P<0.01). The levels of urinic protein and blood lipid in Ginkgo leaf group were significantly lower than those in prednisome plus dipyridamole group (P<0.05). CONCLUSION: The extract from Ginkgo biloba leaf can lower blood lipid levels and urinic protein in children with NS and improve their clinical syptoms and the renal function, therefore has much clinical value as an adjuvant treatment of steroid therapy in such children.
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Ginkgo biloba/química , Hipercolesterolemia/tratamiento farmacológico , Síndrome Nefrótico/complicaciones , Fitoterapia , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Adolescente , Niño , Preescolar , Dipiridamol/uso terapéutico , Quimioterapia Combinada , Femenino , Glucocorticoides/uso terapéutico , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/complicaciones , Lípidos/sangre , Masculino , Inhibidores de Fosfodiesterasa/uso terapéutico , Prednisona/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To observe the effects of glycyrrhizin on laminin (LN) expression in kidney tissue and excretory quantity of urine protein of rats with adriamycin nephropathy, and to explore the protective effects of glycyrrhizin on glomerulosclerosis. METHODS: Eighteen SD rats were randomly divided into 3 groups: normal control group (n=6), untreated group (n=6) and glycyrrhizin-treated group (n=6). Adriamycin nephropathy was induced in rats in the last two groups by intravenous injection of adriamycin. The rats in the glycyrrhizin-treated group were fed glycyrrhizin for eight weeks, whereas the rats in the normal control group and untreated group were fed normal saline solution for eight weeks too. The levels of 24 h urine protein (Upr), serum creatinine (sCr), blood urea nitrogen (BUN) and serum cholesterol (Ch) of rats in each group were examined before treatment and after the treatment for four and eight weeks. The renal morphological changes were observed under a microscope. The expression level of LN in renal tissue was detected by streptavidin-biotin peroxidase complex (SABC) method. RESULTS: The levels of 24 h Upr after the treatment for four and eight weeks in the glycyrrhizin-treated group were both significantly decreased as compared with those in the untreated group. The pathological morphological changes of renal tissue in the glycyrrhizin-treated group were remarkably alleviated, and the expression level of LN in renal tissue was also decreased in the glycyrrhizin-treated group as compared with those in the untreated group. CONCLUSION: The glycyrrhizin exerts certain protective effects on adriamycin nephropathy in rats by reducing excretory quantity of urine protein, decreasing expression level of LN in renal tissue, improving renal function and lessening the severity degree of glomerulosclerosis so as to retard the development of glomerulosclerosis.