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1.
Curr Med Res Opin ; 37(6): 917-927, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33729889

RESUMO

BACKGROUND: To develop a sensitive and clinically applicable risk assessment tool identifying coronavirus disease 2019 (COVID-19) patients with a high risk of mortality at hospital admission. This model would assist frontline clinicians in optimizing medical treatment with limited resources. METHODS: 6415 patients from seven hospitals in Wuhan city were assigned to the training and testing cohorts. A total of 6351 patients from another three hospitals in Wuhan, 2169 patients from outside of Wuhan, and 553 patients from Milan, Italy were assigned to three independent validation cohorts. A total of 64 candidate clinical variables at hospital admission were analyzed by random forest and least absolute shrinkage and selection operator (LASSO) analyses. RESULTS: Eight factors, namely, Oxygen saturation, blood Urea nitrogen, Respiratory rate, admission before the date the national Maximum number of daily new cases was reached, Age, Procalcitonin, C-reactive protein (CRP), and absolute Neutrophil counts, were identified as having significant associations with mortality in COVID-19 patients. A composite score based on these eight risk factors, termed the OURMAPCN-score, predicted the risk of mortality among the COVID-19 patients, with a C-statistic of 0.92 (95% confidence interval [CI] 0.90-0.93). The hazard ratio for all-cause mortality between patients with OURMAPCN-score >11 compared with those with scores ≤ 11 was 18.18 (95% CI 13.93-23.71; p < .0001). The predictive performance, specificity, and sensitivity of the score were validated in three independent cohorts. CONCLUSIONS: The OURMAPCN score is a risk assessment tool to determine the mortality rate in COVID-19 patients based on a limited number of baseline parameters. This tool can assist physicians in optimizing the clinical management of COVID-19 patients with limited hospital resources.


Assuntos
COVID-19 , Medição de Risco/métodos , COVID-19/epidemiologia , COVID-19/mortalidade , China , Hospitalização/estatística & dados numéricos , Humanos , Itália , Fatores de Risco
2.
Cell Metab ; 33(2): 258-269.e3, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33421384

RESUMO

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.


Assuntos
Corticosteroides/uso terapêutico , COVID-19/tratamento farmacológico , Linfócitos/citologia , Neutrófilos/citologia , Corticosteroides/efeitos adversos , Área Sob a Curva , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Tempo de Internação , Modelos de Riscos Proporcionais , Curva ROC , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
3.
Med (N Y) ; 2(1): 38-48.e2, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33043313

RESUMO

Background: The coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown. Methods: In this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death. Findings: The prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA. Conclusions: The dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage. Funding: This study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.

5.
Cell Metab ; 32(2): 176-187.e4, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592657

RESUMO

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Idoso , Enzima de Conversão de Angiotensina 2 , Betacoronavirus/efeitos dos fármacos , COVID-19 , Comorbidade , Infecções por Coronavirus/mortalidade , Síndrome da Liberação de Citocina/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Pneumonia Viral/mortalidade , Estudos Retrospectivos , SARS-CoV-2
6.
Cell Metab ; 31(6): 1068-1077.e3, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32369736

RESUMO

Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.


Assuntos
Glicemia/análise , Infecções por Coronavirus/mortalidade , Diabetes Mellitus Tipo 2/sangue , Índice Glicêmico/fisiologia , Hiperglicemia/sangue , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças/patologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/complicações , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/mortalidade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2
7.
Kidney Dis (Basel) ; 6(2): 109-118, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32309293

RESUMO

Background: The relationship between magnesium and mortality in hemodialysis patients has been evaluated in several prospective studies, but few have assessed the risk of all-cause mortality in elderly hemodialysis patients. The aim of this study was to evaluate the association between magnesium levels and the risk of cardiovascular and overall mortality in elderly maintenance hemodialysis patients. Methods: This was a retrospective study, and patients undergoing maintenance hemodialysis were screened for eligibility at a single dialysis center between July and December 2016. Patients were divided into two groups based on their magnesium levels: a low magnesium level group and a high magnesium level group. Associations between magnesium level and risk of cardiovascular and all-cause mortality were analyzed with a Cox proportional hazards regression model. Results: In total, 413 patients were included with a median follow-up period of 12 months. We found that compared to patients with high magnesium levels, those with low magnesium levels had significantly lower levels of hemoglobin, urea, creatinine, uric acid, phosphate, potassium, chloride, albumin, and spKt/V (p < 0.05 for each parameter). There was a strong correlation between the baseline mean serum magnesium concentration 1 year prior and the concentration 1 year later (r2 = 0.519, p < 0.001). After adjustment for confounding factors, multivariate Cox proportional hazards analysis showed hypomagnesemia to be an independent predictor of all-cause and cardiovascular mortality in chronic hemodialysis patients. Furthermore, subgroup analysis was performed, revealing that serum magnesium levels were still strongly associated with all-cause mortality and cardiovascular mortality in patients older than 60 years, with HR values of 0.020 (95% CI 0.001-0.415) and 0.010 (95% CI 0.000-0.491), respectively. In addition, there were still significant associations between the serum magnesium level and all-cause mortality and cardiovascular mortality in elderly dialysis patients at the 6-month follow-up visit. Conclusion: Our study indicates that lower serum magnesium levels are strongly associated with cardiovascular and all-cause mortality in maintenance hemodialysis patients, especially in the short term and in those who are elderly. Factors affecting serum magnesium concentrations in hemodialysis patients should be investigated, and correcting hypomagnesemia may benefit elderly hemodialysis patients.

8.
Front Med (Lausanne) ; 7: 109, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318578

RESUMO

Aims: The aim of this study was to identify the predictive role of baseline anti-erythropoietin (anti-EPO) antibody levels in follow-up EPO demand in maintenance dialysis patients with end-stage renal disease (ESRD). Methods: Baseline routine blood parameters, clinical data, dialysis-related parameters, EPO, anti-EPO antibody, and anti-EPO-receptor antibody were also measured. Differences in the abovementioned variables were compared among four intervals of the EPO demand index (EDI). Further univariate and adjusted logistic regression analyses were performed to identify the independent predictors for higher EPO demand. Results: The predialysis potassium ion concentration was significantly higher in the fourth quartile (Q4) population than in the other three populations (p < 0.05). Furthermore, the anti-EPO antibody level showed significant differences among the four intervals (p = 0.006). The baseline anti-EPO antibody level was correlated with the follow-up EDI (r 2 = 0.0377, p = 0.030). Furthermore, the follow-up EDI was significantly higher in the anti-EPO antibody-positive group (p = 0.02). Age (OR = 1.071, p = 0.005), ferritin (OR = 1.001, p = 0.038), potassium ion concentration before dialysis (OR = 2.781, p = 0.012), dialysis duration (OR = 1.025, p = 0.030), and anti-EPO antibody level (OR = 7.694, p = 0.004) were potential predictors for higher EPO demand. After adjustment, age (OR = 1.072, p = 0.026), potassium ion concentration before dialysis (OR = 3.425, p = 0.013), and EPO level (OR = 5.27, p = 0.007) were independent predictors for higher EDI demand. Conclusion: The baseline anti-EPO antibody level combined with an older age and a higher predialysis potassium ion concentration are independent predictors for a higher follow-up EPO demand in maintenance dialysis patients with ESRD.

9.
PLoS One ; 10(6): e0127540, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26035439

RESUMO

BACKGROUND: Interleukin-10 (IL-10) is an important immunomodulatory cytokine. Several studies focused the association between IL-10 promoter gene polymorphisms and graft rejection risk in kidney transplantation recipients. However, the results of these studies remain inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations. METHODS: The PubMed, Embase, and Ovid Medline databases were searched. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity. RESULTS: A total of 16 studies including 595 rejection patients and 1239 stable graft patients were included in order to study the IL-10 -1082 (rs1800896 G/A), -819 (rs1800871 C/T), -592 (rs1800872 C/A) and IL-10 (-1082,-819,-592) polymorphisms. The -1082 G/A polymorphism was not associated with an increased graft rejection risk (OR = 1.03; 95%CI, 0.85-1.25, P = 0.74 for GA+AA vs. GG model). Moreover, all of the -819 C/T (OR = 1.06, 95%CI, 0.79-1.42, P = 0.70 for TA+TT vs. CC model), -592 C/A (OR = 1.10, 95% CI, 0.85-1.42, P = 0.47 for AC+AA vs. CC model) and IL-10 (-1082,-819,-592) polymorphisms (OR = 1.00, 95%CI, 0.79-1.27, P = 0.98 for I+L vs. H model) did not increase the graft rejection risk. In addition, we also performed subgroup analysis by ethnic group (mainly in Europeans or Asians) and rejection type (acute or chronic). There was also lack of evidence of a significant association between the IL-10 gene polymorphism and graft rejection risk. The present meta-analysis indicated that the IL-10 gene polymorphism was not associated with graft rejection risk in kidney transplantation recipients. CONCLUSION: This meta-analysis found evidence that the IL-10 polymorphism does not increase the risk of graft rejection in kidney transplantation recipients. Further chronic rejection and other ethnic population studies are needed to confirm our results.


Assuntos
Rejeição de Enxerto/genética , Interleucina-10/genética , Transplante de Rim/efeitos adversos , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Humanos
10.
Toxicol Rep ; 2: 1194-1199, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-28962461

RESUMO

OBJECTIVE: To analyze the clinical features and prognosis of patients suffering from fish bile poisoning. METHODS: A total of 156 multiple organ failure (MOF) patients caused by fish bile poisoning were hospitalized in our department over the past 28 years. The patients' symptoms, examination results, treatment and outcomes were collected and analyzed. RESULTS: All patients' first symptom was gastrointestinal discomfort, including unbearable nausea and intractable vomiting. The symptoms that followed were oliguria or anuria, edema, headache, fatigue, jaundice, palpitation, alimentary tract hemorrhage, gross hematuria, dyspnea, shock, tachycardia, bradycardia, arrhythmia, coma, and cardiac arrest. The symptom severity and cohort were different among different patients. Twenty-one cases received gastroscopy, which exhibited diffuse gastric mucosal bleeding. Twelve patients received renal biopsy, which exhibited focal necrosis of tubular epithelial cells. One patient received a liver biopsy, which exhibited extensive hepatocyte necrosis. All patients received blood purification therapy. Of the four patients who died, 4 out of 5 organs had failed. The general mortality rate was 2.6%. CONCLUSIONS: Compared with the MOF caused by trauma and sepsis, the fish bile poisoning MOF has a much lower morality rate. However, patients with higher age, more underlying diseases, and more organ failure tended to have a worse prognosis.

11.
J Nephrol ; 27(1): 29-36, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24424721

RESUMO

BACKGROUND: Activation and infiltration of T cells and macrophages are key features of renal tubulointerstitial injury. The costimulatory molecule V-set and immunoglobulin domain-containing protein-4 (VSIG4), which is exclusively expressed on macrophages, is capable of inhibiting the T cell response. However, it is unclear whether VSIG4 is involved in renal tubulointerstitial injury. This study was designed to investigate the role of VSIG4 in renal tubulointerstitial injury and the related T cell infiltration. METHODS: The unilateral ureteric obstruction (UUO) model of renal inflammation and tubulointerstitial fibrosis was established in VSIG4 transgenic knock-out C57BL/6 mice (VSIG4(-/-)) and wild-type C57BL/6 mice (VSIG4(+/+)). Comparative analysis of renal biological indices were assessed by quantitative real-time PCR and immunofluorescence staining. RESULTS: Both the VSIG4(-/-) and VSIG4(+/+) mice showed UUO-related temporal changes in renal expression of CD3, CD4 and CD8 T cell markers, with the protein levels being significantly lower in the VSIG4(+/+) UUO mice. Moreover, at each time point examined the UUO VSIG4(+/+) mice showed significantly lower renal mRNA levels of the cytokines interleukin (IL)-2, interferon- and tumor necrosis factor-, but significantly higher IL-10, than the UUO VSIG4(-/-) mice. CONCLUSIONS: The macrophage-expressed VSIG4 may act to alleviate renal tubulointerstitial injury via inhibition of T cell infiltration and secretion of inflammation related factors.


Assuntos
Túbulos Renais/patologia , Macrófagos/metabolismo , Nefrite/imunologia , Nefrite/patologia , RNA Mensageiro/metabolismo , Receptores de Complemento/metabolismo , Animais , Complexo CD3/metabolismo , Antígenos CD4/metabolismo , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos , Fibrose , Interferon gama/genética , Interleucina-2/genética , Interleucinas/genética , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Complemento/genética , Fator de Necrose Tumoral alfa/genética , Obstrução Ureteral/complicações
12.
Mol Med Rep ; 7(4): 1223-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23381841

RESUMO

Sinomenine has been used to treat autoimmune diseases for centuries. However, little is known about its exact mechanisms of action. Whether sinomenine has an effect on programmed death­1 (PD­1) ligands (PD­Ls) in vivo remains unclear. The present study aimed to determine the effect of sinomenine on the expression of PD­L1 and PD­L2 in peripheral blood mononuclear cells (PBMCs). A total of 25 patients with mesangial proliferative nephritis (MsPGN) were treated with sinomenine and followed up for 3 months. The expression of PD­L1 and PD­L2 was studied by using real­time RT­PCR and flow cytometric analysis, and recorded at months 0, 1 and 3 within the PBMCs. The intra­renal expression of PD­L1 and PD­L2 was studied by immunohistochemistry. The results revealed that the PBMCs from the MsPGN patients expressed high levels of PD­L1 at the mRNA and protein levels compared with the healthy donors. Immunohistochemistry revealed an increased PD­L1 expression in the renal tissues from the MsPGN patients. Sinomenine was observed to have a significant effect in decreasing the PD­L1 expression in the PBMCs. The present study therefore suggests a novel mechanism for the therapeutic effects of sinomenine on MsPGN in vivo.


Assuntos
Antígeno B7-H1/biossíntese , Leucócitos Mononucleares/efeitos dos fármacos , Morfinanos/administração & dosagem , Nefrite/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Receptor de Morte Celular Programada 1/biossíntese , Esclerose/tratamento farmacológico , Adulto , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Mesângio Glomerular/metabolismo , Mesângio Glomerular/patologia , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Nefrite/metabolismo , Nefrite/patologia , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , Esclerose/metabolismo , Esclerose/patologia
13.
Mol Vis ; 17: 153-8, 2011 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-21245953

RESUMO

PURPOSE: Several studies suggest that vascular dysregulation play a role in the etiology of glaucoma. In the present study, we aimed to investigate the association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG). METHODS: There were 102 POAG and 88 PCAG patients, diagnosed on the basis of clinical history, raised intraocular pressure (IOP), cup-to-disc ratio (CDR) and visual field defects, and 120 age- and sex-matched control subjects genotyped for 5 tagging single nucleotide polymorphisms (SNPs; rs743507, rs3793342, rs11771443, rs7830, and rs3918188) of the human eNOS gene. RESULTS: rs3793342, rs743507, rs11771443, rs7830, and rs3918188 were not found to be associated with POAG or with PCAG. In the haplotype-based case-control analysis, the frequency of the C-T haplotype established by rs3793342 and rs11771443 was significantly higher for POAG patients than for control subjects (p<0.001, OR=5.111, 95%CI=1.766~14.788). CONCLUSIONS: The C-T haplotype established by rs3793342 and rs11771443 may be genetic marks of POAG in the Han Chinese population.


Assuntos
Glaucoma de Ângulo Fechado/genética , Glaucoma de Ângulo Aberto/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Idoso , Algoritmos , Estudos de Coortes , Feminino , Marcadores Genéticos , Genótipo , Haplótipos , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Polimorfismo de Nucleotídeo Único
14.
Ren Fail ; 32(7): 863-70, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20662701

RESUMO

BACKGROUND AND AIMS: It has been well documented that endothelial progenitor cells (EPCs) participate in neovascularization in adults and that rarefaction of peritubular capillaries (PTCs) is closely associated with progressive kidney disease. Therefore, we investigated whether EPCs were influenced by conditioned medium (CM) of renal tubular epithelial cells (RTECs) stimulated by hypoxia, to provide evidence for EPCs transplantation in vivo in the future. METHODS: Mononuclear cells of rat bone marrow were isolated by density gradient centrifugation and were cultured according to previously described techniques. RTECs were cultured primarily with routine tissue block adhering wall method. In addition, CM was harvested from RTECs cultivated for 48 h in 5% O(2). EPCs proliferation and migration were evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and transwell. The protein and mRNA expression of stromal cell-derived factor (SDF-1), vascular endothelial growth factor (VEGF), angiogenin 1 (Ang-1), and C-X-C chemokine receptor 4 (CXCR4) was separately assessed by Western blot, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase-polymerase chain reaction (RT-PCR) methods. RESULTS: We showed that hypoxia increased the expression of SDF-1 and VEGF in RTEC. In addition, hypoxic CM improved proliferation, migration, and expression of VEGF, Ang-1, and CXCR4 of EPCs. CONCLUSIONS: These results suggest that hypoxic CM improves neovascularization of EPCs and may also be considered as therapeutic agents to supply the potent origin of reconstituion of PTCs of progressive kidney disease.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/fisiologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Túbulos Renais/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/fisiologia , Animais , Hipóxia Celular , Células Cultivadas , Meios de Cultivo Condicionados/farmacocinética , Masculino , Ratos , Ratos Sprague-Dawley
15.
Int Immunopharmacol ; 9(7-8): 894-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19336263

RESUMO

Sinomenine has been used to treat autoimmune diseases for centuries. However, the mechanism underlying its therapeutic effects remains unknown. Increasing recognition of the importance of the Th1/Th2 imbalance in nephritis has raised the questions of whether there is a Th1/Th2 imbalance in patients with mesangial proliferative nephritis (MsPGN) and whether sinomenine can modulate the Th1/Th2 imbalance. In this study, 25 MsPGN patients were treated with sinomenine and followed for 3 months. The expression of T-bet and GATA-3 mRNA in peripheral blood mononuclear cells (PBMCs) and the serum levels of interferon-gamma (IFN-gamma), interleukin (IL)-4, and IL-10 were studied at month 0, month 1, and month 3. The intra-renal expression of T-bet and GATA-3 was studied via immunohistochemistry. Results reveal that PBMCs from MsPGN patients expressed high levels of T-bet mRNA and low levels of GATA-3 mRNA, and the T-bet/GATA-3 ratio in MsPGN patients was significantly higher than that in healthy donors. Meanwhile, MsPGN patients were found to have simultaneously elevated IFN-gamma values and decreased IL-10 values. Immunohistochemistry revealed increased T-bet and decreased GATA-3 expression in renal tissues from MsPGN patients. Moreover, sinomenine was found to cause a decrease in T-bet mRNA expression, resulting in a drop in the T-bet/GATA-3 ratio. Sinomenine was also found to elicit a decrease in the serum levels of IFN-gamma. These results suggest that a shift toward the Th1 pathway of Th cell activation occurs in MsPGN patients, and that sinomenine has the potential to counter this shift in the Th1/Th2 balance and thereby produce therapeutic effects.


Assuntos
Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Rim/metabolismo , Morfinanos/administração & dosagem , Células Th1/metabolismo , Células Th2/metabolismo , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/imunologia , Fator de Transcrição GATA3/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/genética , Glomerulonefrite Membranoproliferativa/patologia , Homeostase , Humanos , Imuno-Histoquímica , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-4/sangue , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Proteínas com Domínio T/genética , Proteínas com Domínio T/imunologia , Proteínas com Domínio T/metabolismo , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/patologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/patologia
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