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1.
J Transl Med ; 20(1): 510, 2022 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335368

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is among the most important causes for chronic kidney disease. Anthocyanins (ANT) are polyphenolic compounds present in various food and play an important role in ameliorating hyperglycemia and insulin sensitivity. However, the effects of ANT in DKD are still poorly understood. This study aimed to investigate the effect of ANT (cyanidin-3-O-glucoside [C3G]) on the renal function of DKD, and whether the anti-DKD effect of ANT is related to metabolic pathways. METHODS: To explore the role of ANT in DKD, we performed the examination of blood glucose, renal function, and histopathology. As for the mechanism, we designed the label-free quantification proteomics and nontargeted metabolomics analysis for kidney and serum. Subsequently, we revealed the anti-DKD effect of ANT through the bioinformatic analysis. RESULTS: We showed that the fasting blood glucose level (- 6.1 mmol/L, P = 0.037), perimeter of glomerular lesions (- 24.1 µm, P = 0.030), fibrosis score of glomerular (- 8.8%, P = 0.002), and kidney function (Cystatin C: - 701.4 pg/mL, P = 0.043; urine creatinine: - 701.4 mmol/L, P = 0.032) were significantly alleviated in DKD mice after ANT treatment compared to untreated in the 20th week. Further, proteins and metabolites in the kidneys of DKD mice were observed to be dramatically altered due to changes in amino acid metabolism with ANT treatment; mainly, taurine and hypotaurine metabolism pathway was upregulated (P = 0.0001, t value = 5.97). Furthermore, upregulated tryptophan metabolism (P < 0.0001, t value = 5.94) and tyrosine metabolism (P = 0.0037, t value = 2.91) pathways had effects on serum of DKD mice as responsed ANT regulating. CONCLUSIONS: Our results suggested that prevention of the progression of DKD by ANT could be related to the regulation of amino acid metabolism. The use of dietary ANT may be one of the dietary strategies to prevent and treat DKD.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Camundongos , Animais , Nefropatias Diabéticas/metabolismo , Antocianinas/farmacologia , Antocianinas/uso terapêutico , Glicemia , Rim/patologia , Aminoácidos , Diabetes Mellitus/patologia
2.
Stem Cells Dev ; 30(5): 227-233, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33397195

RESUMO

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the production of multiple autoimmune antibodies and potentially involves any organ or tissue with a broad range of clinical manifestations. Conventional therapy still utilizes glucocorticoids and immunosuppressants. However, some patients show inadequate responses to glucocorticoids and immunosuppression, which may induce secondary immune dysfunction and severe infection as well as lead to an increased tumor risk. The lack of in vitro models has hampered progress in understanding and treating SLE. Patient-derived induced pluripotent stem cells (iPSCs) may provide a unique opportunity for modeling in vitro diseases as well as a platform for drug screening in individual patients. We isolated peripheral blood mononuclear cells from blood to explore the establishment of an in vitro model platform for SLE and directly purified CD34+ cells and seeded them for expansion. CD34+ cells were forced to express seven pluripotency factors, OCT4, SOX2, NANOG, LIN28, c-MYC, KLF4, and SV40LT, through transduction in lentiviral vectors. The morphological characteristics of induced pluripotent stem-like cells, such as prominent nucleoli and a high nucleus-to-cytoplasm ratio, were observed. The pluripotency of established SLE patient-derived iPSCs was confirmed by the expression of embryonic stem cell (ESC) markers and the ability of cells to differentiate into multiple cell lines. SLE patient-derived iPSCs exhibited human ESC properties, including morphology; growth characteristics; expression of pluripotency, genes, and surface markers; and teratoma formation. In conclusion, we generated SLE patient-derived iPSCs and validated their pluripotency. This study is a first but critical step that can provide a model platform for research aimed at understanding the SLE mechanism, which may lead to the discovery of new targets or compounds for the treatment of this disease.


Assuntos
Antígenos CD34/metabolismo , Regulação da Expressão Gênica , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Adulto , Antígenos de Superfície/metabolismo , Células Cultivadas , Feminino , Citometria de Fluxo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Cariotipagem , Leucócitos Mononucleares/citologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Proteína Homeobox Nanog/genética , Fator 3 de Transcrição de Octâmero/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Antígenos Embrionários Estágio-Específicos/metabolismo
3.
J Steroid Biochem Mol Biol ; 199: 105591, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31954177

RESUMO

Maternal smoking during pregnancy affects fetal neurological development. Metabolomic studies in the general population suggest that smoking is associated with characteristic metabolic alterations. We investigated the association between the maternal smoking status, the fetal metabolome and head circumference at birth, as a surrogate parameter of brain development. 320 mother/newborn pairs of the Berlin Birth Cohort were investigated. Anthropometric parameters, including head circumference, of newborns of smoking mothers, former smoking mothers, and never smoking mothers were compared to assess the impact of maternal smoking behavior. Associations between maternal smoking behavior and 163 cord blood metabolites and associations between newborn head circumference and concentrations of smoking behavior related metabolites were analysed. Male newborns of smoking mothers had a reduced head circumference when compared with newborns from former smoking and never smoking mothers (p < 0.05). Using linear regression models corrected for established confounding factors, maternal smoking during pregnancy showed an independent association with head circumference (95% CI: -0.75~-0.41 cm, p = 2.45×10-11). In a stepwise linear regression model corrected for known confounding factors of brain growth lyso-phosphatidylcholine 20:3 (95% CI: 6.68~39.88 cm, p = 4.62×10-4) was associated with head circumference in male offspring only. None of the metabolites were associated with head circumference of female newborns. In conclusion, maternal smoking during pregnancy impacted on male offspring's development including brain development. The smoking related metabolite lyso-phosphatidylcholine 20:3 was associated with head circumference of male offspring.


Assuntos
Encéfalo/metabolismo , Sangue Fetal/metabolismo , Cabeça/anatomia & histologia , Fumar/efeitos adversos , Adulto , Antropometria , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Feminino , Humanos , Recém-Nascido , Masculino , Mães , Fosfatidilcolinas/sangue , Gravidez
4.
BMC Nephrol ; 20(1): 150, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039758

RESUMO

BACKGROUND: The serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China. METHODS: We recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR). RESULTS: We found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis. CONCLUSIONS: The present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.


Assuntos
Complemento C3/análise , Glomerulonefrite por IGA/diagnóstico , Imunoglobulina A/sangue , Proteinúria/sangue , Adulto , Fatores Etários , Análise de Variância , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pontuação de Propensão , Curva ROC , Análise de Regressão , Fatores Sexuais
5.
Cell Physiol Biochem ; 45(2): 614-624, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29402770

RESUMO

BACKGROUND/AIMS: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. METHODS: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. RESULTS: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14: 0, 16: 1, and 18: 1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94×10-11 ). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: -258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). CONCLUSIONS: After correction for multiple testing and adjustment for potential confounders, LPC 16: 1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies.


Assuntos
Peso ao Nascer , Sangue Fetal/metabolismo , Lisofosfatidilcolinas/análise , Adulto , Feminino , Humanos , Recém-Nascido , Modelos Lineares , Lisofosfatidilcolinas/química , Masculino , Metabolômica , Gravidez , Fatores Sexuais , Fumar , Espectrometria de Massas em Tandem
6.
Cell Physiol Biochem ; 45(2): 625-638, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29402850

RESUMO

BACKGROUND/AIMS: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. METHODS: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. RESULTS: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32: 1 and proline still showed an independent association with GDM. CONCLUSIONS: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM.


Assuntos
Diabetes Gestacional/patologia , Sangue Fetal/metabolismo , Soro/metabolismo , Adulto , Índice de Massa Corporal , Estudos de Coortes , Diabetes Gestacional/metabolismo , Feminino , Humanos , Modelos Logísticos , Metabolômica , Fosfatidilcolinas/análise , Fosfatidilcolinas/química , Gravidez , Prolina/análise , Fatores de Risco , Fumar , Espectrometria de Massas em Tandem
7.
Cell Adh Migr ; 12(2): 109-117, 2018 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-25588050

RESUMO

Renal cell carcinoma (RCC) is the third most frequent malignancy within urological oncology. However, the mechanisms responsible for RCC metastasis are still needed further illustration. Our present study revealed that a seven-transmembrane receptor G-protein coupled estrogen receptor (GPER) was highly detected in various RCC cell lines such as ACHN, OS-RC-2 and SW839. The activation of GPER by its specific agonist G-1 significantly promoted the in vitro migration and invasion of ACHN and OS-RC-2 cells. G-1 also up regulated the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. The inhibitor of MMP-9 (Cat-444278), but not MMP-2 (Sc-204092), abolished G-1 induced cell migration, which suggested that MMP-9 is the key molecule mediating G-1 induced RCC progression. Further, G-1 treatment resulted in phosphorylation of AKT and ERK in RCC cells. PI3K/AKT inhibitor (LY294002), while not ERK inhibitor (PD98059), significantly abolished G-1 induced up regulation of MMP-9 in both AHCN and OS-RC-2 cells. Generally, our data revealed that activation of GPER by its specific agonist G-1 promoted the metastasis of RCC cells through PI3K/AKT/MMP-9 signals, which might be a promising new target for drug discovery of RCC patients.


Assuntos
Carcinoma de Células Renais/metabolismo , Receptor alfa de Estrogênio/agonistas , Neoplasias Renais/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Neoplasias Renais/tratamento farmacológico , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/metabolismo
8.
Medicine (Baltimore) ; 96(26): e7373, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28658162

RESUMO

BACKGROUND & AIMS: Nutritional interventions for malnutrition in cancer patients can be helpful. However, concise intervention recommendations remain controversial. Thus, the aim of this study was to report on a nutrition intervention conducted by a multidisciplinary team of specialist nurses and to explore the effect of nutritional intervention on cancer patients. METHODS: This prospective clinical trial study enrolled 110 colorectal cancer patients undergoing chemotherapy. The patients were evaluated upon admission using the 2002 Nutritional Risk Screening system (NRS-2002). The patients were randomly divided into intervention and control groups including 55 patients each. Patients in the control group were administered a normal diet, while those in the intervention group received individual recipes developed by a team of professional nurses, clinical doctors, dietitian, family caregivers, and the patients themselves. Patient weight and serum albumin and prealbumin levels were compared between the 2 groups at different time points. RESULTS: There was a significant difference in patient weight and serum albumin and prealbumin levels before and after nutrition intervention in the intervention group (P < .05). In the control group, weight did not change during ordinary diet guidance. Serum albumin level was slightly improved after 12 cycles of chemotherapy, similar to the prealbumin results. There were statistically significant differences in serum albumin and prealbumin levels between the intervention and control groups after nutrition intervention (P < .05). However, there was no statistically significant difference in weight between the groups after nutrition intervention (P > .05). CONCLUSION: A multidisciplinary team approach for nutrition intervention conducted by specialist nurses improved prealbumin levels in colorectal cancer patients undergoing chemotherapy, with no weight change.


Assuntos
Neoplasias Colorretais/dietoterapia , Neoplasias Colorretais/tratamento farmacológico , Enfermeiros Especialistas , Equipe de Assistência ao Paciente , Biomarcadores Tumorais/sangue , Peso Corporal , Cuidadores , Neoplasias Colorretais/sangue , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Nutricionistas , Educação de Pacientes como Assunto , Albumina Sérica/análise , Resultado do Tratamento
9.
Oncotarget ; 8(28): 45391-45398, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28512268

RESUMO

BACKGROUND: Advance directives are a sensitive issue among traditional Chinese people, who usually refrain from mentioning this topic until it is imperative. Medical decisions for cancer patients are made by their families, and these decisions might violate patients' personal will. OBJECTIVES: This study aimed to examine the acceptance of advance directives among Chinese cancer patients and their families and patient participation in this procedure and, finally, to analyze the moral risk involved. RESULTS: While 246 patients and their family members refused official discussion of an advance directive, the remaining 166 patients and their families accepted the concept of an advance directive and signed a document agreeing to give up invasive treatment when the anti-cancer treatment was terminated. Of these, only 24 patients participated in the decision making. For 101 patients, anti-cancer therapy was ended prematurely with as many as 37 patients not told about their potential loss of health interests. MATERIALS AND METHODS: Participants were 412 adult cancer patients from 9 leading hospitals across China. An advance directive was introduced to the main decision makers for each patient; if they wished to sign it, the advance directive would be systematically discussed. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between families and patients, patients' awareness of their disease, and participation in an advance directive. CONCLUSIONS: Advance directives were not widely accepted among Chinese cancer patients unless anti-cancer therapy was terminated. Most cancer patients were excluded from the discussion of an advance directive.


Assuntos
Diretivas Antecipadas , Tomada de Decisões , Neoplasias/epidemiologia , Neoplasias/psicologia , Preferência do Paciente , Adulto , Idoso , Conscientização , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Participação do Paciente
10.
Kidney Int ; 91(5): 1236-1242, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28215666

RESUMO

Myeloid-derived suppressor cells (MDSCs) are recently identified immune suppressive cells in multiple chronic inflammations. Here, we investigated MDSCs in patients with end-stage renal disease (ESRD) and their clinical significance in these patients and healthy individuals (49 each). Polymorphonuclear and mononuclear MDSCs were investigated by flow cytometry. Patients with ESRD before hemodialysis presented a significantly higher level of polymorphonuclear MDSCs. Depletion of polymorphonuclear-MDSCs resolved T cell IFN-γ responses. By co-culture, T cell proliferation and the production of IFN-γ were abrogated by the addition of polymorphonuclear MDSCs in a dose-dependent manner. Both of these effects were reversed by a reactive oxygen species inhibitor. The levels of reactive oxygen species were higher in polymorphonuclear MDSCs derived from patients with ESRD than from normal individuals. The mRNA level of NOX2, the key protein complex responsible for reactive oxygen species production, was higher in ESRD-related polymorphonuclear MDSCs. The phospho-STAT3 level, a key activator of MDSCs, was higher in ESRD-related polymorphonuclear MDSCs. Finally, the polymorphonuclear MDSC level before and after hemodialysis was positively related to infectious diseases. Patients with ESRD were dichotomized into 2 groups by the amount of polymorphonuclear MDSCs. Patients with high levels of polymorphonuclear MDSCs presented with a higher incidence of infectious events. Thus, polymorphonuclear MDSCs were elevated in ESRD patients with strong immune-suppressive capability through a phospho-STAT3/reactive oxygen species pathway. Hence, polymorphonuclear MDSCs might increase the risk of infectious complications.


Assuntos
Tolerância Imunológica/imunologia , Infecções/imunologia , Falência Renal Crônica/imunologia , Células Supressoras Mieloides/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Técnicas de Cocultura , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Incidência , Infecções/epidemiologia , Interferon gama/imunologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Células Supressoras Mieloides/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Estudos Prospectivos , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Diálise Renal , Fator de Transcrição STAT3/metabolismo , Linfócitos T/fisiologia , Adulto Jovem
11.
J Huazhong Univ Sci Technolog Med Sci ; 34(6): 875-881, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25480584

RESUMO

Estrogen-related receptor alpha (ERRα) plays an important role in the development of hormone-dependent cancers, but its roles in lung cancer remain elusive. The present study was aimed to investigate the effects of ERRα on the proliferation and metastasis of lung cancer A549 cells. The mRNA and protein levels of ERRα were detected in lung cancer A549 and MCF-7 cells and bronchial epithelial BEAS-2B cells by qRT-PCR and Western blotting, respectively. ERRα plasmid transfection and XCT-790 (an inverse agonist of ERRα) were used to up-regulate or down-regulate ERRα expression in A549 cells, respectively. The viability of A549 cells was measured by cell counting kit-8 (CCK-8) and the motility of A549 cells by wound healing assay and Transwell migration/invasion assay. The epithelial markers E-cadherin (E-Cad) and zona occludin-1 (ZO-1), the mesenchymal markers fibronectin (FN) and vimentin (Vim) and the transcription factors (Snail, Zeb1 Twist and Slug) were further detected at mRNA and protein levels by qRT-PCR and Western blotting, respectively. The results showed that ERRα promoted the growth of lung cancer A549 cells in vitro. XCT-790 significantly inhibited the migration and invasion of A549 cells. Over-expression of ERRα promoted the epithelial-to-mesenchymal transition (EMT) of A549 cells, down-regulated the epithelial makers E-Cad and ZO-1, and up-regulated the mesenchymal makers FN and Vim. Silencing of Slug, but not other transcription factors, significantly abolished the ERRα-induced EMT of A549 cells. It was suggested that ERRα promoted the migration and invasion of A549 cells by inducing EMT, and Slug was involved in the process. Targeting ERRα might be an efficient approach for lung cancer treatment.


Assuntos
Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/biossíntese , Receptores de Estrogênio/biossíntese , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/prevenção & controle , Metástase Neoplásica , Proteínas de Neoplasias/genética , Receptores de Estrogênio/genética , Receptor ERRalfa Relacionado ao Estrogênio
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