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This paper investigated the global attractive set for quaternion-valued neural networks (QVNNs) with leakage delay, time-varying delay, and neutral items. Based on various basic conditions of activation function, the global attractive set and global exponential attractive set of QVNNs are given combined with novel analytical techniques and Lyapunov theory. The QVNNs are studied by a direct method, without any decomposition. The time delay can be non-differential, which makes the results more pragmatic. Restrictions on the activation function of the neutral item are relaxed. The neutral activation function can be bounded or unbounded, which makes the results more practical. Two simulation examples are given to verify the validity of the theory results.
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PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) have been proved to be hazardous to health. Previous studies have focused on the distribution and sources of PAHs, whereas there is little knowledge of the damage to organs. Here we sought to investigate the pollution level and seasonal variation characteristics of PAHs in PM2.5 in Xi'an and assess the health risk, to establish a PAHs exposure model, and investigate the toxicological effects of PAHs on the respiratory and immune functions. A sub-chronic exposure model of PAHs was established by inhalation. The pathological changes of lung tissues were observed with a light microscope. Inflammatory reactions in alveolar lavage fluid were determined using the corresponding kit. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were detected with enzyme linked immunosorbent assay (ELISA) kit; the proliferation of lymphocytes in spleen was detected with methyl tetrazolium (MTT); DNA immune damage was determined with DNA gel electrophoresis. The results showed that (1) the total concentration of 16 PAHs ranged from 41.1 to 387 ng/m3, with a mean value of 170 ng/m3, and the concentration of PAHs in PM2.5 was higher in winter than in other seasons. (2) The sources of PAHs in the atmosphere of Xi'an urban area were mainly coal combustion, and the equivalent carcinogenic concentration of PAHs in PM2.5 was 3.9 ng/m3. (3) Foreign body granuloma formation and inflammatory cell damage were observed in the lungs of rats infected with toxin; the levels of reactive oxygen species (ROS) and mobile device assistant (MDA) increased while nitric oxide synthase (NOS) decreased with the increase of dose; the expression levels of IL-6 and IL-8 elevated with the increase of toxin dose, showing an obvious dose-effect relationship; the level of PAHs damage to cells showed a dose-effect relationship. Sub-chronic exposure to PAHs could cause sustained inflammatory injury to the organism. Measures should be taken to counter the problems of PAHs in PM2.5 in Xi'an and relevant health promotion strategies should be developed.
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Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Animais , Ratos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Estações do Ano , Interleucina-8 , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Interleucina-6/análise , Baço , Material Particulado/toxicidade , Material Particulado/análise , China , Medição de RiscoRESUMO
The present study compared Chinese emerging adults and adults regarding the association between contamination fear, posttraumatic stress disorder post-COVID-19 and psychiatric comorbidity after controlling for demographic and trauma exposure variables. 1089 Chinese civilians (M = 382; F = 707) with a mean age of 26 years (M = 26.36, SD = 8.58) were recruited from different provinces in China via an online survey posted on mainstream Chinese social networking platforms. They completed a demographic page with questions on trauma exposure, the Vancouver Obsessional Compulsive Inventory, the Posttraumatic Stress Disorder Checklist for DSM-5 and the General Health Questionnaire-28. Results showed that 12.7%, 68.7% and 18.6% met criteria for full, partial and no PTSD, respectively. Emerging adults reported significantly lower levels of symptoms of re-experiencing, avoidance, somatic problems, anxiety and fear of contamination than adults. In both emerging adults and adults, contamination fear was correlated with PTSD and psychiatric comorbidity. High educational attainment was significantly correlated with psychiatric comorbidity in emerging adults, but with PTSD in adults. Length of quarantine was correlated with psychiatric comorbidity only in adults. In conclusion, both emerging adults and adults developed varying levels of contamination fear, posttraumatic stress and general psychological symptoms following the outbreak of COVID-19. Emerging adults were more resilient than adults in coping with distress.
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Mesangial proliferative glomerulonephritis (MesPGN) is a common renal disease that lacks effective drug intervention. Aconiti Lateralis Radix (Fuzi), a natural Chinese medical herb, is found with significant therapeutic effects on various diseases in the clinic. However, its effects on MesPGN have not been reported. This study is aimed to discuss the therapeutic effects of the aqueous extract of Aconiti Lateralis Radix (ALR) and the polysaccharides of Aconiti Lateralis Radix (PALR) on MesPGN as well as the underlying mechanism. In this study, we, firstly, studied the anti-MesPGN mechanism of ALR and PALR. ALR and PALR inhibit the proliferation of the mesangial cells through the PI3K/AKT/mTOR pathway, induce the G0/G1 phase of block and apoptosis, inhibit the activity of Cyclin E and CDK2, increase the expression of Bax, cleaved caspase-8/caspase-8, and cleaved caspase-3/caspase-3 proteins, and effectively inhibit the growth of the mesangial cells. Overall, our data suggest that ALR and PALR may be potential candidates for MesPGN and that PALR is more effective than ALR.
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Recurrent spontaneous abortion (RSA) remains a critical and challenging problem in reproduction. To discover novel biomarkers for RSA, ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) metabolomics approach was applied to detect RSA serum metabolic profiles and explore its possible pathogenesis and mechanism. The abortion rat model was established, and a metabolomics analysis was performed to evaluate the differentially expressed metabolites between the control and model groups. Immunohistochemistry (IHC), qRT-PCR, and Western blot further examined the expression of Arachidonic acid metabolism-related genes in uterus tissues. To identify arachidonic acid metabolism-related changes in RSA, ELISA's potential mechanisms were further confirmed in serum. Ninety-one metabolites were significantly different between the two groups, as indicated by a VIP ≥1, fold change ≥1. The metabolic pathways involving arachidonic acid metabolism pathway (P = 0.00044) are related to RSA. Verification by experimental showed that compared with the control rats, the expression of the COX-1, COX-2, PTGFR, and TBXA2R genes associated with the arachidonic acid metabolism pathway has significantly increased the uterus and serum of RSA rats (P < 0.05). Regulation of the arachidonic acid metabolism pathway might serve as a promising therapeutic strategy for relieving RSA women's symptoms.
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Aborto Habitual/sangue , Ácido Araquidônico/sangue , Cromatografia Líquida de Alta Pressão/métodos , Regulação da Expressão Gênica , Metabolômica/métodos , Prenhez , Espectrometria de Massas em Tandem/métodos , Animais , Ácido Araquidônico/química , Biomarcadores/sangue , Ciclo-Oxigenase 1/sangue , Ciclo-Oxigenase 2/sangue , Feminino , Imuno-Histoquímica , Masculino , Proteínas de Membrana/sangue , Redes e Vias Metabólicas , Metaboloma , Gravidez , Prostaglandinas/sangue , Ratos , Ratos Endogâmicos Lew , Receptores de Prostaglandina/sangue , Receptores de Tromboxano A2 e Prostaglandina H2/sangueRESUMO
We investigated whether there was activation of NLRP1 inflammasomes and excessive autophagy in oxidative stress damage. And we further demonstrate whether there is a cascade relationship between the activation of NLRP1 inflammasomes and the phenomenon of excessive autophagy. To observe the expression level of the NLRP1 inflammasome group in the pathological process of trophoblast cell oxidative stress, western blot, immunofluorescence, and qRT-PCR were performed. Autophagy in trophoblast cells after the action of H2O2 was detected by using normal trophoblast cells' NLRP1-specific activator (MDP) as a positive control. The presence of excessive autophagy was determined by comparing it with the autophagy-related proteins in normal trophoblast cells. Through siRNA-NLRP1, we investigated the role of oxidative stress and the NLRP1 inflammasome in autophagy in cells. 100 µmol MDP for 24 hours can be used as the optimal concentration of the NLRP1 activator. In human placental trophoblast oxidative stress, the model group significantly increased the expression level of inflammasome IL-1ß, CASP1, and NLRP1, compared with the control group NLRP3, and LC3-II, Beclin-1, ATG5, ATG7, and p62 overactivated the autophagy ability of cells. After the activation of NLRP1, the expression of these inflammasomes increased, accompanied by the decrease in autophagy. After the expression of NLRP1 was silenced by RNAi, the expression of inflammasome IL-1ß, CASP1, and NLRP3 was also decreased. Still, the autophagy level was increased, which was manifested by the high expression of LC3-II, Beclin-1, ATG5, and ATG7 and the decrease in p62. Trophoblast cells showed the expression of NLRP1 protein and excessive autophagy under oxidative stress. Simultaneously, the NLRP1 inflammasome of trophoblast cells in the state of oxidative stress was correlated with autophagy. Inflammasome activation and autophagy were shown to be linked and to influence each other mutually. These may also provide new therapeutic targets in a pathological pregnancy.
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Inflamassomos/metabolismo , Proteínas NLR/metabolismo , Estresse Oxidativo/fisiologia , Placenta/metabolismo , Trofoblastos/metabolismo , Autofagia/fisiologia , Linhagem Celular , Feminino , Humanos , Proteínas NLR/genética , Placenta/patologia , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Trofoblastos/patologiaRESUMO
Low temperature plasma (LTP) technology has shown an outstanding application value in the pharmaceutical filed in recent ten years. This paper reviews the research advances in LTP, including its effects on enhancing or inhibiting drug activity, its combined use with drugs to treat cancers, its effects on the improvement of drug delivery system, its use in preparation of new inactivated virus vaccines, its use with mass spectrometry for rapid detection of drug quality, and the anti-tumor and sterilization effects of plasma-activated liquids. The paper also analyzes the challenges of LTP in the pharmaceutical filed, hoping to promote related research.
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OBJECTIVE: To determine the effect of Wenyang Huazhuo Fang (WHF), a Traditional Chinese Medicine decoction, on renal function in a rat model of doxorubicin-induced nephropathy, and to elucidate the underlying mechanism. METHODS: Sprague-Dawley rats were randomly divided into six groups: control, doxorubicin-nephropathy, and prednisone-treated (6.45 mg·kg-1·dï¼1) doxorubicin nephropathy groups, as well as high- (7.26 g·kg-1·dï¼1, medium- (2.42 g·kg-1·dï¼1, and low-dose (0.81 g·kg-1·dï¼1 WHF-treated doxorubicin-nephropathy groups. The nephropathy rat model was established by two tail vein injections of doxorubicin, followed by prednisone or WHF treatment for 8 weeks. Body weights were monitored and urinary protein was measured every 2 weeks. After the end of the treatment period, the rats were euthanized. Serum biochemical indicators were determined and renal morphological alterations were assessed using histological staining. The expression of transient receptor potential cation channel subfamily C member 6 (TRPC6), stromal interaction molecule 1 (STIM1), and calcium release-activated calcium channel protein 1 (Orai1) was detected using western blotting, and their mRNA levels were examined using quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: WHF treatment was found to significantly ameliorate weight loss, proteinuria, hypoalbuminemia, and dyslipidemia in doxorubicin-nephropathy rats. The protein and mRNA levels of TRPC6, STIM1, and Orai1 were partially, but significantly suppressed by prednisone or WHF treatment. CONCLUSION: Treatment with WHF significantly ameliorates renal injury in a rat model of doxorubicin-induced nephropathy, which could be at least partially related to repression of the TRPC6 pathway.
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Doxorrubicina/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Nefropatias/prevenção & controle , Substâncias Protetoras/administração & dosagem , Canais de Cátion TRPC/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/genética , Nefropatias/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPC/genéticaRESUMO
Human cervical cancer is one of the most common malignancies worldwide. Recent studies have focused on microRNAs that play crucial roles in cancer development and progression of cervical cancer. In this study, we aimed to analyse the biological function of microRNA-543 in cervical cancer. Samples of human cervical cancer and matched adjacent normal cervical tissues were collected, and expression level of microRNA-543 and the clinical characteristics of cervical cancer were investigated. We found that microRNA-543 expression was significantly elevated in cervical cancer and its aberrant expression levels were positively correlated with tumour size ( p = 0.0315), differentiation ( p = 0.0134), clinical stage ( p = 0.0315) and overall ( p = 0.0426) and disease-free survival ( p = 0.0396) of cervical cancer. Overexpression of microRNA-543 in cancer-derived HeLa and SiHa facilitated cell growth and suppressed cell apoptosis, while down-regulation of microRNA-543 exerted a reverse effect on cell growth and apoptosis. In addition, we demonstrated that BRCA1-interacting protein 1 was directly regulated by microRNA-543 and the restoration of BRCA1-interacting protein 1 expression reversed the effects of microRNA-543 on cell proliferation. Taken together, these findings collectively demonstrate that microRNA-543 exerts its oncogene function by directly targeting BRCA1-interacting protein 1 in cervical cancer, indicating a potential novel potential prognostic biomarker and therapeutic target for cervical cancer.
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Proteínas de Ligação a DNA/metabolismo , MicroRNAs/biossíntese , RNA Helicases/metabolismo , Neoplasias do Colo do Útero/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Proliferação de Células/fisiologia , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Proteínas de Grupos de Complementação da Anemia de Fanconi , Feminino , Células HeLa , Humanos , MicroRNAs/genética , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , RNA Helicases/genética , Transfecção , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: Hippocampus plays an important role in spatial learning and memory. Ghrelin, a brain-gut peptide, participates in the mnestic functions of hippocampus through its receptor growth hormone secretagogue receptor (GHS-R) distributed in hippocampus. This study was to investigate whether there was a correlation between the changes of ghrelin system in hippocampus and the spatial cognitive impairment caused by chronic renal failure (CRF). METHODS: Sprague-Dawley rats (male, 180 ± 10 g, 7-8 weeks old) were randomly classified into CRF group and control group (n = 18 per group). The CRF model was constructed by 5/6 nephrectomy and the controls treated with sham operation. By the 8th week after the surgery, the spatial cognitive function of rats was assessed by Morris water-maze test (MWM), the protein expression of ghrelin and GHS-R in the hippocampus by immunohistochemistry, and the mRNA expression by real-time PCR. Statistical analysis was performed using ANOVA, Student-Newman-Keuls-q test and Pearson correlation analysis, and P < 0.05 was considered significant. RESULTS: Compared with the controls, the time spent in "platform" quadrant (TSPQ) of rats with CRF was decreased, but the escape latency (EL) was increased significantly in MWM, and meanwhile the protein and mRNA expression of ghrelin and GHS-R in hippocampus was also increased significantly (P < 0.05 or P < 0.01). Correlation analysis suggested that the TSPQ was negatively but the EL was positively correlated with the mRNA expression of ghrelin and GHS-R (P < 0.01). CONCLUSION: The CRF-caused changes of ghrelin system in hippocampus might be correlated with the CRF-caused cognitive function impairment.
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Disfunção Cognitiva/metabolismo , Grelina/metabolismo , Hipocampo/metabolismo , Falência Renal Crônica/complicações , Receptores de Grelina/metabolismo , Uremia/metabolismo , Animais , Disfunção Cognitiva/etiologia , Grelina/genética , Masculino , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores de Grelina/genética , Navegação Espacial , Uremia/complicaçõesRESUMO
OBJECTIVE: To investigate the effects of artemisinin against proteinuria and glomerular filtration barrier damage in rats with adriamycin-induced nephropathy, and the potential mechanism underpinned the action. METHODS: Forty adriamycin rats were randomly divided into two groups with the ratio of 1 : 3; the small-number group served as control group (n = 10), and the rats in the large-number group were treated with adriamycin to induce nephropathy; then they were further randomly assigned into 3 subgroups: benazepril group (n = 10), artemisinin group (n = 10), and adriamycin group (n = 10). The benazepril group and artemisinin group were treated with benazepril suspl (5.0 mg/kg daily) and artemisinin suspl (150 mg/kg daily) respectively after being modeled; those in the control group and adriamycin group were intragastrically administered an equivalent volume of distilled water every day. The treatment after model establishment lasted for a total of 4 weeks. The 24 h uric protein, blood biochemicals, renal pathological changes, renal ultrastrutural changes, Nephrin and Podocin proteins and gene expressions were measured by Coomassie brilliant blue assay, completely automatic biochemical analyzer, light microscope, electron microscopy, Western blot and reverse transcription polymerase chain reaction, respectively. RESULTS: The rats in adriamycin group showed a significant increase in 24 h uric protein excretion, serum total cholesterol (TC), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (Scr) and decrease in albumin (Alb) (P < 0.05 or P < 0.01). Compared with adriamycin group, artemisinin could reduce uric protein excretion, decrease the serum TC, TG elevation, increase the serum Alb level, up-regulate the expressions of Nephrin and Podocin (P < 0.05 or P < 0.01), but no statistical significance effects on the levels of BUN, Scr in artemisinin group (P > 0.05). The renal pathological and ultrastrutural observation indicate that artemisinin could attenuate the severity of foot process effacement and fusion in the nephropathic rats. CONCLUSION: Artemisinin might have an effect on the nephropathy in rats caused by adriamycin, which may be at least partly correlated with attenu- ation of the severity of foot process effacement and fusion, up-regulation of the expressions of Nephrin and Podocin in the glomeruli in the rats.
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Artemisininas/administração & dosagem , Doxorrubicina/efeitos adversos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Nefropatias/tratamento farmacológico , Proteínas de Membrana/genética , Proteinúria/tratamento farmacológico , Animais , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/genética , Nefropatias/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Proteinúria/induzido quimicamente , Proteinúria/genética , Proteinúria/metabolismo , RatosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Although the exact mechanism(s) underlying acupuncture remain unknown, acupuncture and acupuncture-like somatic nerve stimulation have been used to treat different kidney diseases and several complications related to them.The aim of this preliminary study was to assess the effectiveness of acupuncture on glomerulonephritis (GN) according to the theory of "Wind-hided renal collaterals" previously proposed. MATERIAL AND METHODS: We used a New Zealand white rabbit model of cationized bovine serum albumin (cBSA)-induced glomerulonephritis and then administered them metoprolol, irbesartan or acupuncture to evaluate the effectiveness of acupuncture treatment and preliminarily explore its potential mechanism. RESULTS: After immunization, our results showed that compared to the cBSA+MET and cBSA+IRB medication groups, "Qufeng Tongluo" significantly lowered parameters of renal function and improved podocyte injury in the 3rd, 6th and 8th weeks of treatment. Moreover, acupuncture increased the protein expression of phosphorylated ERK1/2. CONCLUSIONS: Our study suggests that a potential mechanism by which acupuncture has an antihypertensive effect and can significantly halt deteriorating renal function due to cBSA GN might be mediated by inhibiting the Erk1/2 MAPK pathway to reduce renal sympathetic nerve activity (RSNA).
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Terapia por Acupuntura/métodos , Glomerulonefrite/terapia , Animais , Compostos de Bifenilo/farmacologia , Modelos Animais de Doenças , Progressão da Doença , Glomerulonefrite/fisiopatologia , Irbesartana , Rim/inervação , Rim/fisiopatologia , Testes de Função Renal , Metoprolol/farmacologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Podócitos/patologia , Coelhos , Soroalbumina Bovina/administração & dosagem , Sistema Nervoso Simpático/metabolismo , Tetrazóis/farmacologia , Fatores de TempoRESUMO
OBJECTIVE: To determine the effect of Qufeng Tongluo Recipe (QFTLR) on the expressions of connexin 36 (Cx36) protein and gene in rat mesangial cells (MCs) and the proliferation of the MCs. METHODS: Serum samples containing Benazepril (Bena) and QFTLR were prepared in line with serum pharmacology methodology. The MCs cultured in vitro were divided into normal control and Lipopolysaccharide (LPS), Bena and QFTLR treated groups. The expressions of Cx36 protein and gene were detected by laser scanning confocal microscope (LSCM), Western blot, immunohistochemical assay and quantitative real time polymerase chain reaction (QRT-PCR) respectively. RESULTS: Compared with the control, higher level of Cx36 protein expression was found in the MCs than treated with LPS (P < 0.01). Both Bena and QFTLR lowered the level of Cx36 protein expression in the MCs treated with LPS significantly (P < 0.01 or P < 0.05). Similar results were found with the expression of Cx36 mRNA. CONCLUSION: QFTLR inhibits the proliferation of rat MCs, possibly through down-regulating the expressions of Cx36 protein and gene.
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Conexinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Células Mesangiais/efeitos dos fármacos , Animais , Benzazepinas/farmacologia , Proliferação de Células , Lipopolissacarídeos/farmacologia , Células Mesangiais/metabolismo , RNA Mensageiro , Ratos , Proteína delta-2 de Junções ComunicantesRESUMO
OBJECTIVE: To study the effects and possible underlying mechanism of Qufeng Tongluo Prescription (, QFTL) on the regulation of mesangial cells (MCs) proliferation and apoptosis. METHODS: The MCs used in this experiment have undergone five passages induced by lipopolysaccharide (LPS). Changes in the proliferation, apoptosis, cell cycle regulatory proteins and mRNA expression levels of the MCs after administration of Benazepril or QFTL were measured by methyl thiazolyl tetrazolium (MTT) reduction assay, flow cytometry, Western blot and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RESULTS: The addition of Benazepril or QFTL serum inhibited LPS-induced MC proliferation after treatment for 24, 48 and 72 h, respectively (P<0.05 or P<0.01). Moreover, the inhibitory effect is more significant in the QFTL group at 48 h (P<0.05). Compared with the control group, LPS-induced cell proliferation decreased the number of cells in G1 phase versus cells in S and G2/M phases, while the addition of QFTL and Benazepril serum increased the ratio of cells at G1 phase (P<0.05 or P<0.01) to cells at S phase (P<0.01), implicating the cell cycle inhibition effect exerted by QFTL. LPS decreased the level of MC apoptosis, compared with the control group (P<0.05), while QFTL and Benazepril serum increased the level of MC apoptosis (P<0.01). Moreover, the difference between the QFTL group and the Benazepril group was statistically significant (P<0.01). Compared with the control group, the protein and mRNA expression levels of cylinD1, cyclin dependent kinase 2 (CDK2) and p21 were significantly increased (P<0.05 or P<0.01), p27 was decreased but with no statistical significance (P>0.05); After being treated with QFTL and Benazepril serum, the protein and mRNA expression levels of cylinD1, CDK2, p21 were decreased and p27 increased significantly (P<0.05 or P<0.01); Compared with the Benazepril group, QFTL show better effects on protein and mRNA expression levels of cylinD1, CDK2 (P<0.05 or P<0.01) and p21 protein expression (P<0.05). CONCLUSION: QFTL inhibits MCs proliferation, promotes MCs apoptosis through an underlying mechanism of down-regulating the protein and mRNA expression levels of cylinD1, CDK2, p21 and up-regulation of the expression level of p27.
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Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Mesângio Glomerular/efeitos dos fármacos , Animais , Sequência de Bases , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Primers do DNA , Citometria de Fluxo , Mesângio Glomerular/citologia , Mesângio Glomerular/metabolismo , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a polypeptide member of the transforming growth factor ß superfamily of cytokines and performs many cellular functions. Its overexpression may lead to renal fibrosis. AIM: This study planed to investigate the effects of TGF-ß1 on the cell cycle and phenotype of mesangial cells. METHODS: Rat mesangial cells were cultured together with different concentrations (0, 1, 2, 5, and 10 ng/mL) of TGF-ß1 for specified times from 0 min to 72 h. 0 ng/mL TGF-ß1 and 0 min served as controls. Cell cycles were assessed by flow cytometry and α-smooth muscle actin expression (α-SMA) protein expression by western blot analysis. All data were presented as Mean ± SD. Statistical analysis was performed by using one-way analysis of variance and correlation analysis. Results were considered significant at p < 0.05. RESULTS: After 15 min of co-culture with different concentrations of TGF-ß1, the percentage of mesangial cells in G0/G1 phase was significantly elevated compared to the control (p < 0.05). 12 h co-culture induced cell hyperplasia, 24 h co-culture obvious up-regulation of α-SMA (p < 0.01) and one or two cells' myofibroblast phenotype transition, and 36 h co-culture several cells' phenotype transition. Correlation analysis prompted that the TGF-ß1-induced premature aging was time-dependent (p < 0.01). CONCLUSION: TGF-ß1 may induce mesangial cells' premature senescence and myofibroblast-like phenotype transformation time-dependently, which may contribute to the development of early stage of glomerulosclerosis.
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Ciclo Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Células Mesangiais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Actinas/metabolismo , Animais , Técnicas de Cultura de Células , Técnicas de Cocultura , Células Mesangiais/citologia , Células Mesangiais/fisiologia , Ratos , Fatores de TempoRESUMO
OBJECTIVE: To observe the effect of acupuncture on cationized bovine serum albumin (C-BSA) nephritis model in rabbits and to explore its mechanism. METHODS: Fifty rabbits were randomly divided into a blank group, a model group, a metoprolol group, a irbesartan group and an acupuncture group, 10 rabbits in each group. The model was established by ear vein intravenous injection with C-BSA. The positive control groups were treated by intragastric administrated with metoprolol and irbesartan, respectively. The acupuncture group was treated by acupuncture at "Fengmen" (BL 12) and "Shenshu" (BL 23). No interventions were added on the blank group and the model group. The changes of blood pressure (BP), heart rate (HR), plasma norepinephrine (NE), serum creatinine (Scr), blood urea nitrogen (BUN) and 24 hours urine protein (24 h UP) in rabbits at the time points of 3rd, 6th and 8th week of treatment were observed. RESULTS: After the model was established, the Scr of (194.30 +/- 20.09) micromol/L, BUN of (9.19 +/- 0.66) mmol/L and 24 h UP of (277.70 +/- 20.09) mg/24 h in the model group were all higher than the Scr of (66.03 +/- 4. 76) micromol/L, BUN of (4.11 +/- 0.71) mmol/L and 24 h UP of (14.28 +/- 1. 47) mg/24 h in the blank group (all P < 0.01), and the diffused mesenteria hyperplasia and the increase of intercapillary cells in the model group were showed in the pathological sections. After 3 weeks of treatment. The Scr of (99.82 +/- 9.29) micromol/L, BUN of (6.32 +/- 0.75) mmol/L and 24 h UP of (189.67 +/- 15.45) mg/ 24 h in the acupuncture group were all decreased significantly, furthermore, the decrease of BP, HR, NE were better than the other treatment groups (P < 0.05, P < 0.01). Except the level of 24 h up and HR at 8th week, other results were as same as the 3rd week. CONCLUSION: Acupuncture can improve the function of kidney, decrease the content of 24 h UP and the underlying therapeutic mechanism could be correlated with that acupuncture can lower excitability of sympathetic nerve and alleviate the renal pathological lesion induced by nephritis.
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Terapia por Acupuntura , Rim/fisiopatologia , Nefrite/terapia , Pontos de Acupuntura , Animais , Pressão Sanguínea , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Humanos , Rim/patologia , Masculino , Nefrite/metabolismo , Nefrite/patologia , Nefrite/fisiopatologia , CoelhosRESUMO
OBJECTIVE: To observe the effects of Qufengtongluo Recipe (QFTLR) on the expressions of cell cycle regulatory proteins in rat mesangial cells (MCs) in vitro and investigate the mechanism by which QFTLR inhibits MC proliferation. METHODS: Using the methods of serum pharmacology, we studied the expressions of cell cycle regulatory proteins in rat MCs treated with QFTLR by laser scanning confocal microscope and immunohistochemistry. RESULTS: Compared with the normal control cells, the cells challenged with lipopolysaccharide (LPS) showed significantly enhanced expressions of cyclin D1, CDK2, and P21 (P<0.01) and obviously lowered protein expression of P27 (P<0.01). Treatment of the LPS-challenged cells with QFTLR and benazepril both resulted in significantly attenuated expressions of cyclin D1, CDK2, and P21 and obvious increase of P27 expression (P<0.05 or P<0.01), but QFTLR produced stronger effects than benazepril in regulating of cyclinD1, P21 and P27 protein expressions (P<0.05 or P<0.01). CONCLUSION: QFTLR inhibits rat MC proliferation in vitro possibly by down-regulating the cellular expressions of cyclin D1, CDK2, and P21 and up-regulating the expression of P27 protein.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/metabolismo , Animais , Linhagem Celular , Ciclina D1/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Células Mesangiais/citologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effects of Artemisinin on the expressions of GRalpha mRNA, GRbeta mRNA and P300/CBP protein in lupus nephritis mice. METHODS: Forty hybrid female mice were randomly and equally divided into four groups with the method of random number table: control group, model group, prednisone group administrated with 6.45 mg/kg Artemisinin (Art) suspension. A mice model of LN was established by injection with living lymph cell suspension. The expressions of GC receptor alpha (GRalpha) mRNA, GC receptor beta (GRbeta) mRNA in peripheral blood mononuclear cells (PBMCs), and transcriptional coactivator P300/CBP protein in renal tissue were respectively measured by the technique of RT - PCR and immunohistochemical assay. RESULTS: Compared with the model group. The expression of transcriptional coactivator P300/CBP protein in renal tissue and GRa mRNA in PBMCs of treatment groups was increased significantly, GRbeta mRNA expression was significantly decreased (P < 0.05 or P < 0.01). And the Art group had a better effect on the expression of GRalpha mRNA and transcriptional coactivator P300/CBP protein than that of the prednisone group (P < 0.01). CONCLUSION: The underlying therapeutic mechanism may be correlated with the regulation of Art on the expressions of GRalpha mRNA, GRbeta mRNA in PBMC and transcriptional coactivator P300/CBP protein in renal tissue.
Assuntos
Artemisininas/farmacologia , Leucócitos Mononucleares/metabolismo , Nefrite Lúpica/metabolismo , Receptores de Glucocorticoides/metabolismo , Fatores de Transcrição de p300-CBP/metabolismo , Animais , Artemisia annua/química , Artemisininas/administração & dosagem , Modelos Animais de Doenças , Feminino , Leucócitos Mononucleares/efeitos dos fármacos , Nefrite Lúpica/tratamento farmacológico , Camundongos , Camundongos Endogâmicos , Prednisona/administração & dosagem , Prednisona/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição de p300-CBP/genéticaRESUMO
OBJECTIVE: To investigate the therapeutic effects and mechanisms of using artemisinin (Art) combined with glucocorticoid (GC) to treat lupus nephritis (LN) mice. METHODS: Forty hybrid female mice were randomly and equally divided into four groups with the method of random number table: control group, model group, prednisone group administrated with 6.45 mg/(kg·d) prednisone suspension, and Art+prednisone group administrated with 150 mg/(kg·d) Art suspension and 3.225 mg/(kg·d) prednisone suspension. A mice model of LN was established by injection with living lymph cell suspension. The changes of urine protein/24h, the expressions of GC receptor α (GRα) mRNA, GC receptor ß (GRß) mRNA in peripheral blood mononuclear cells (PBMCs), and transcriptional coactivator P300/CBP protein in renal tissue were measured. RESULTS: Compared with the model group, the treatment groups had significant decrease in urine protein/24 h, and renal pathological lesion (P<0.01). In the same groups, the expression of transcriptional coactivator P300/CBP protein in renal tissue and GRα mRNA were significantly increased, and GRß mRNA expression was significantly decreased (P<0.01). And the Art+prednisone group has a better therapeutic effect than the prednisone group (P<0.01). CONCLUSIONS: Art has therapeutic sensitization effects on GC in the LN mice. The underlying mechanism could be correlated with the effect of Art on the increase of the expressions of GRα mRNA and transcriptional coactivator P300 300/CBP protein in renal tissue and on the decrease of the expression of GRß mRNA in PBMC.
Assuntos
Artemisininas/farmacologia , Modelos Animais de Doenças , Nefrite Lúpica/metabolismo , Prednisona/farmacologia , RNA Mensageiro/genética , Receptores de Glucocorticoides/genética , Fatores de Transcrição de p300-CBP/metabolismo , Animais , Artemisininas/administração & dosagem , Sequência de Bases , Primers do DNA , Eletroforese em Gel de Ágar , Feminino , Nefrite Lúpica/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Prednisona/administração & dosagem , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In this study, we investigated the therapeutic effect of artemisinin (Art) on lupus nephritis mice and its mechanisms by comparing the differences between lupus nephritis (LN) mice given Art and control mice in molecular biology, immunohistochemistry, and histopathology. The results showed that Art could remarkably relieve the symptoms, decrease the level of urine protein/24 h, and alleviate pathological renal lesions. The differences among the four groups in the expression of the NF-κBp65 protein, nuclear factor-κB (NF-κB) activity, and the expression of transforming growth factor-ß1 (TGF-ß1) mRNA in renal tissue suggested that Art can lower the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibit the expression of the NF-κBp65 protein and NF-κB and TGF-ß1 mRNA in the renal tissues of LN mice. These results proved that it is reliable and effective to use Art to treat LN mice, and its therapeutic mechanisms should closely be related to the fact that Art can obviously decrease the serum levels of TNF-α and IL-6 and down-regulate the expression of the NF-κBp65 protein and NF-κB and TGF-ß1 mRNA in renal tissues.