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1.
Int J Med Sci ; 21(1): 19-26, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164356

RESUMO

Purpose: This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) to assess the kidneys' quality before procurement. Methods: This prospective study included 74 donors and 148 recipients of kidneys. 119 kidneys underwent quantitative analysis. Before organ procurement, potential kidney donors underwent CEUS, though organ procurement involved a zero-point puncture biopsy. CEUS parameters of the renal cortex and medulla were evaluated, including rise time (RT), time to peak (TTP), the area under the curve (AUC), wash-in slope (WIS), peak intensity (PI), and mean transit time (MTT). Donors' kidneys were classified based on their pathological. Additionally, short-term clinical indicators of renal recipients were collected and analyzed to determine whether the patients had delayed recovery of renal allograft function. Results: This experiment included 148 cases of kidney information, divided into two groups based on the Remuzzi score of the kidneys. However, 29 kidneys were excluded from the quantitative analysis due to loss or low quality of CEUS images. Comparing the time-intensity curve (TIC) of renal cortical region of interest (ROI), we found that the group with lower pathological scores exhibited higher PI (P=0.002), AUC(P=0.003), and WIS (P=0.009). TIC comparison results for renal medulla ROI revealed that the group with lower pathological scores had higher PI (P=0.010), AUC (P=0.023), and WIS (P=0.024). Conclusions: This study highlighted the potential of CEUS as a non-invasive, safe, and real-time examination method that correlates with the Remuzzi score and renal pathology. Therefore, it can be used as a prospective preoperative non-invasive evaluation method for the donor's kidney.


Assuntos
Transplante de Rim , Humanos , Estudos Prospectivos , Meios de Contraste , Rim/diagnóstico por imagem , Rim/patologia , Ultrassonografia/métodos
2.
Curr Med Sci ; 43(3): 514-519, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37115399

RESUMO

OBJECTIVE: Delayed graft function (DGF) and early graft loss of renal grafts are determined by the quality of the kidneys from the deceased donor. As "non-traditional" risk factors, serum biomarkers of donors, such as lipids and electrolytes, have drawn increasing attention due to their effects on the postoperative outcomes of renal grafts. This study aimed to examine the value of these serum biomarkers for prediction of renal graft function. METHODS: The present study consecutively collected 306 patients who underwent their first single kidney transplantation (KT) from adult deceased donors in our center from January 1, 2018 to December 31, 2019. The correlation between postoperative outcomes [DGF and abnormal serum creatinine (SCr) after 6 and 12 months] and risk factors of donors, including gender, age, body mass index (BMI), past histories, serum lipid biomarkers [cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (DL)], and serum electrolytes (calcium and sodium) were analyzed and evaluated. RESULTS: (1) Donor age and pre-existing hypertension were significantly correlated with the incidence rate of DGF and high SCr level (≥2 mg/dL) at 6 and 12 months after KT (P<0.05); (2) The donor's BMI was significantly correlated with the incidence rate of DGF after KT (P<0.05); (3) For serum lipids, merely the low level of serum HDL of the donor was correlated with the reduced incidence rate of high SCr level at 12 months after KT [P<0.05, OR (95% CI): 0.425 (0.202-0.97)]; (4) The serum calcium of the donor was associated with the reduced incidence rate of high SCr level at 6 and 12 months after KT [P<0.05, OR (95% CI): 0.184 (0.045-0.747) and P<0.05, OR (95% CI): 0.114 (0.014-0.948), respectively]. CONCLUSION: The serum HDL and calcium of the donor may serve as predictive factors for the postoperative outcomes of renal grafts after KT, in addition to the donor's age, BMI and pre-existing hypertension.


Assuntos
Hipertensão , Transplante de Rim , Adulto , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Cálcio , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Hipertensão/complicações , Biomarcadores , Cálcio da Dieta , Lipídeos
3.
Healthcare (Basel) ; 11(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36981481

RESUMO

Improving public willingness toward organ donation is an important solution to the low organ donation rate. This study aimed to explore factors impacting public willingness for organ donation in China from a multi-agent perspective and further explore the impact of these factors on high or low willingness, using a social-ecological framework. Data from a total of 11,028 (effective rate, 94.18%) participants were analysed. Generalised linear model (GLM) and quantile regression were used to explore factors associated with willingness and high/low willingness toward organ donation, respectively. The mean willingness toward organ donation was 56.9 (range, 0-100) points. GLM regression revealed that age, family health, males, lower educational levels, and agricultural hukou were negatively associated with willingness. For personality, conscientiousness was negatively associated with willingness, whereas openness was positively associated with willingness. Health literacy perceived social support, and media utilisation were positively associated with willingness. Quantile regression further indicated that educational levels of college, bachelor, master's, and PhD, openness, health literacy, perceived social support, and media utilisation were positively associated with organ donation willingness at all percentiles. It is necessary to adopt more targeted and diversified publicity, education, and guidance for different types of individuals. Meanwhile, social support needs to be strengthened. To enhance the willingness of the residents to donate organs, media publicity should be strengthened, particularly by using modern ways to improve their health literacy.

4.
Exp Clin Transplant ; 20(11): 1035-1039, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36524890

RESUMO

In recent years, dual-kidney transplant has become an established method to overcome the inferior quality of donor organs and to allow the recovery of discarded human kidneys. However, in some cases, 1 of the 2 donor kidneys is unsuitable for transplant because of severe pathological changes, and the remaining marginal kidney is often discarded regardless of whether it meets criteria for dual-kidney transplant. Here, we report the use of marginal kidneys from 2 different donors, both of whom had missed kidney donation as a result of the serious pathological changes in their contralateral kidney. We combined the 2 donors' marginal kidneys for dual-kidney transplant, which were implanted into the right iliac fossa of the recipient after cold ischemia times of 13 hours 40 minutes and 30 hours 30 minutes, respectively. The recipient had fully recovered and showed favorable renal function without complications at discharge and at the 1.5-year follow-up. To the best of our knowledge, this is the first case report of successful unilateral dual-kidney transplant of discarded kidneys from 2 expanded criteria donors.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Resultado do Tratamento , Doadores de Tecidos , Rim/cirurgia , Rim/fisiologia , Rim/patologia , Isquemia Fria/efeitos adversos , Sobrevivência de Enxerto
5.
Int J Mol Sci ; 23(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35563662

RESUMO

Organ shortage has led to the increasing utilization of livers retrieved from donors after circulatory death (DCD). These pre-damaged organs are susceptible to further warm ischemia and exhibit minimal tolerance for cold storage. The aim was thus to examine the effects of fibrinolysis combined with Venous Systemic Oxygen Persufflation (VSOP) on the preservation of DCD livers in vivo. Livers of male Lewis rats were explanted after 45 min of warm ischemia, cold-stored for 18 h, and transplanted into a recipient animal. Livers were left untreated or underwent either VSOP or fibrinolysis via Streptokinase (SK) or received combined SK and VSOP. Combined treatment exhibited improved microvascular flow at 168 h (p = 0.0009) and elevated microperfusion velocity at 24 h post-transplantation (p = 0.0007). Combination treatment demonstrated increased portal venous flow (PVF) at 3 and 24 h post-transplantation (p = 0.0004, p < 0.0001), although SK and VSOP analogously achieved increases at 24 h (p = 0.0036, p = 0.0051). Enzyme release was decreased for combination treatment (p = 0.0002, p = 0.0223) and lactate dehydrogenase (LDH) measurements were lower at 24 h post-transplantation (p = 0.0287). Further supporting findings have been obtained in terms of serum cytokine levels and in the alterations of endothelial injury markers. The combination treatment of SK + VSOP might provide improved organ integrity and viability and may therefore warrant further investigation as a potential therapeutic approach in the clinical setting of DCD.


Assuntos
Transplante de Fígado , Animais , Fibrinólise , Fígado , Masculino , Preservação de Órgãos , Oxigênio/farmacologia , Perfusão , Ratos , Ratos Endogâmicos Lew
6.
Front Med (Lausanne) ; 9: 838738, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308516

RESUMO

ABO blood group antibodies have not been generated or are at low titer during early infancy. Therefore, in theory, ABO-incompatible kidney transplantation (ABOi KT) may be successfully achieved in small infants without any pre-transplant treatment. We report here the first ABO-incompatible deceased donor kidney transplantation (ABOi DDKT) in an infant. The recipient infant was ABO blood group O, and the donor group A. The recipient was diagnosed with a Wilms tumor gene 1 (WT1) mutation and had received peritoneal dialysis for 4 months prior to transplant. At 7 months and 27 days of age, the infant underwent bilateral native nephrectomy and single-kidney transplantation from a 3-year-old brain-dead donor. No pre- or post-transplantation antibody removal treatment was performed, since the recipient's anti-iso-hemagglutinin-A Ig-M/G antibody titers were both low (1:2) before transplantation and have remained at low levels or undetectable to date. At 11 months post-transplant, the recipient is at home, thriving, with normal development and graft function. This outcome suggests that ABOi DDKT without antibody removal preparatory treatment is feasible in small infants, providing a new option for kidney transplantation in this age range.

7.
Aging (Albany NY) ; 13(3): 4696-4712, 2021 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-33558447

RESUMO

BACKGROUND: The current study aimed to understand the genetic landscape and investigate the diagnostic and prognostic biomarkers of primary hepatocellular carcinoma (HCC). METHODS: A cohort of 36 Chinese HCC samples with hepatitis B virus (HBV) infection was examined by whole-exome sequencing (WES). Prognosis-related alterations were identified and further verified in the TCGA database and GSE65372 profiles in the GEO database. A Chinese replication cohort of 180 HCC samples with HBV infection was collected to evaluate the candidate genes by immunohistochemical analysis. A receiver operating characteristic (ROC) curve analysis evaluated the prognostic power of candidate genes. Finally, EdU and transwell invasion assay were performed to detect the function of candidate genes. RESULTS: A total of 11 novel genes showed a significant association with HCC in the discovery cohort. The data were verified using the GEO and TCGA databases, and the expression of ARID1A, CSMD1, and SENP was evaluated in the replication cohort. Furthermore, ARID1A, CSMD1, and SENP3 are effective prognostic biomarkers for HCC patients in the replication population. CONCLUSIONS: Molecular heterogeneity was detected in HCC patients, and ARID1A, CSMD1, and SENP3 were identified as effective HCC prognosis biomarkers. CSMD1 prevents HCC by suppressing cell invasion.


Assuntos
Carcinoma Hepatocelular , Cisteína Endopeptidases/genética , Proteínas de Ligação a DNA/genética , Neoplasias Hepáticas , Proteínas de Membrana/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Adulto , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Feminino , Hepatite B , Humanos , Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Sequenciamento Completo do Genoma
8.
Magn Reson Med ; 85(5): 2805-2814, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33197060

RESUMO

PURPOSE: Over the last two decades, extended criteria have promoted an increased number of donor livers available for liver transplantation. But posttransplant graft loss is still a major concern. Macrovesicular hepatic steatosis (MHS) is recognized as the most significant prognostic histologic parameter in predicting posttransplant graft loss. We aimed to evaluate the utility of ex vivo volumetric quantitative MRI for quantifying MHS before liver transplantation using proton density fat-fraction (PDFF-MRI) histogram analysis. METHODS: PDFF-MRI was performed at 3.0T in 40 livers. We obtained histogram parameters of whole-liver volume of interest, including the mean, median, 5th, 10th, 25th, 75th, 90th, and 95th percentile PDFF; skewness; kurtosis; entropy; and volume. RESULTS: Livers from 40 cadaveric donors were included, and histologic ex vivo fat quantification was available for 33 livers. Ten livers had MHS and 23 had normal fat content. The MHS group had higher mean, median, 5th, 10th, 25th, 75th, 90th, and 95th percentile PDFF, and entropy than the group with normal fat content (P < .05). Median PDFF had greater area under the curve value than other parameters. Mean PDFF showed an excellent correlation with entropy and a moderate correlation with MHS quantification on histology. CONCLUSIONS: Ex vivo volumetric quantitative PDFF-MRI histogram analysis is a very useful and noninvasive method to detect MHS before liver transplantation. Median PDFF was the best predictor of the presence of MHS. Entropy is a very promising parameter.


Assuntos
Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Prótons
9.
Medicine (Baltimore) ; 99(49): e22808, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285676

RESUMO

With the increasing demand on organ transplants, it has become a common practice to include patients with primary central nervous system (CNS) malignancies as donors given the suggested low probability metastatic spread outside of the CNS. However, an extra-CNS spread of the disease cannot be excluded raising potential risks of cancer transmission from those donors. In order to balance between the risk of donor-derived disease transmission and the curative benefit for the recipient, a careful donor and organ selection is important. We performed a literature research and summarized all reported studies of organ transplants from donors suffered from primary CNS malignancies and determined the risk of tumor transmission to recipients. There were 22 cases of transplant-transmitted CNS tumors onto recipients since 1976. The association risks of cancer transmission were attributed to donor tumor histology, disruption of the blood-brain barrier, cerebrospinal fluid extra-CNS, and false diagnosis of primary intracranial tumor as well as the molecular properties of the primary tumor such as the existence of EGFR-amplification. The association risks and features of CNS tumors transmission recipients indicated that we need to reassess our thresholds for the potential fatal consequences of these donors.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Transplante de Órgãos/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricos , Barreira Hematoencefálica/fisiologia , Líquido Cefalorraquidiano/fisiologia , Humanos , Fatores de Risco , Análise de Sobrevida
10.
J Mol Med (Berl) ; 98(12): 1795-1807, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33159537

RESUMO

SUMOylation has long been recognized to regulate multiple biological processes in pancreatic beta cells, but its impact on proinsulin disulfide maturation and endoplasmic reticulum (ER) stress remains elusive. Herein, we conducted comparative proteomic analyses of SUMOylated proteins in primary mouse/human islets following proinflammatory cytokine stimulation. Cytokine challenge rendered beta cells to undergo a SUMOylation turnover manifested by the changes of SUMOylation substrates and SUMOylation levels for multiple substrates. Our data support that SUMOylation may play a crucial role to regulate proinsulin misfolding and ER stress at least by targeting Protein Disulfide Isomerase a3 (Pdia3). SUMOylation regulates Pdia3 enzymatic activity, subcellular localization, and protein binding ability. Furthermore, SUMOylation of Pdia3 exacerbated proinsulin misfolding and ER stress, and repressed Stat3 activation. In contrast, disruption of Pdia3 SUMOylation markedly rescued the outcomes. Collectively, our study expands the understanding how SUMOylation regulates ER stress in beta cells, which shed light on developing potential strategies against beta cell dysfunction.


Assuntos
Estresse do Retículo Endoplasmático , Células Secretoras de Insulina/metabolismo , Proinsulina/metabolismo , Dobramento de Proteína , Animais , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Camundongos , Proinsulina/química , Isomerases de Dissulfetos de Proteínas/química , Isomerases de Dissulfetos de Proteínas/metabolismo , Proteômica/métodos , Sumoilação
11.
Hepatobiliary Pancreat Dis Int ; 19(4): 378-383, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32622825

RESUMO

BACKGROUND: Long-term survival after liver transplantation (LT) for hepatocellular carcinoma (HCC) patients remains poor because of tumor recurrence. To improve the prognosis of HCC patients after LT, we aimed to identify different transplantation criteria and risk factors related to tumor recurrence and evaluate the effect of preventive chemotherapy in a single center. METHODS: In total, data on 20 variables and the survival of 199 patients with primary HCC who underwent LT between 2005 and 2015 were included for analysis. The patients were divided into the following three groups: Group 1, within the Milan and Hangzhou criteria (n = 51); Group 2, beyond the Milan but within the Hangzhou criteria (n = 36); and Group 3, beyond the Milan and Hangzhou criteria (n = 112). Survival probabilities for the three groups were calculated using multivariate Cox regression analysis. The association between preventive therapy and HCC-recurrence after LT was analyzed by multiple logistic regression analysis. RESULTS: Child-Pugh stage C and hepatitis B virus (HBV) infection were independent risk factors for patients with tumor recurrence who did not meet the Milan criteria. The overall survival rates of the 199 patients showed statistically significant differences among the three groups (P < 0.001). Moreover, no significant difference was noted in the survival rate between Group 1 and Group 2 (P > 0.05). Multivariate logistic regression analysis showed that postoperative prophylactic chemotherapy reduced the risk of tumor recurrence in patients who did not meet the Hangzhou and Milan criteria (OR = 0.478; 95% CI: 0.308-0.741; P = 0.001). CONCLUSIONS: Child-Pugh classification and HBV infection were the independent risk factors of tumor recurrence in HCC patients with LT. The Hangzhou criteria were effective and analogous compared with the Milan criteria. Preventive chemotherapy significantly reduced the risk of recurrence and prolonged the survival time for HCC patients beyond the Milan and Hangzhou criteria after LT.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Transplante de Fígado/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Seleção de Pacientes , Adulto , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Quimioprevenção/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , Análise de Sobrevida
14.
Eur Urol ; 77(6): 748-754, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32317180

RESUMO

BACKGROUND: Previous studies on coronavirus disease 2019 (COVID-19) have focused on populations with normal immunity, but lack data on immunocompromised populations. OBJECTIVE: To evaluate the clinical features and outcomes of COVID-19 pneumonia in kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: A total of 10 renal transplant recipients with laboratory-confirmed COVID-19 pneumonia were enrolled in this retrospective study. In addition, 10 of their family members diagnosed with COVID-19 pneumonia were included in the control group. INTERVENTION: Immunosuppressant reduction and low-dose methylprednisolone therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The clinical outcomes (the severity of pneumonia, recovery rate, time of virus shedding, and length of illness) were compared with the control group by statistical analysis. RESULTS AND LIMITATIONS: The clinical symptomatic, laboratory, and radiological characteristics of COVID-19 pneumonia in the renal transplant recipients were similar to those of severe COVID-19 pneumonia in the general population. The severity of COVID-19 pneumonia was greater in the transplant recipients than in the control group (five severe/three critical cases vs one severe case). Five patients developed transient renal allograft damage. After a longer time of virus shedding (28.4 ± 9.3 vs 12.2 ± 4.6 d in the control group) and a longer course of illness (35.3 ± 8.3 vs 18.8 ± 10.5 d in the control group), nine of the 10 transplant patients recovered successfully after treatment. One patient developed acute renal graft failure and died of progressive respiratory failure. CONCLUSIONS: Kidney transplant recipients had more severe COVID-19 pneumonia than the general population, but most of them recovered after a prolonged clinical course and virus shedding. Findings from this small group of cases may have important implications for the treatment of COVID-19 pneumonia in immunosuppressed populations. PATIENT SUMMARY: Immunosuppressed transplant recipients with coronavirus disease 2019 infection had more severe pneumonia, but most of them still achieved a good prognosis after appropriate treatment.


Assuntos
Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Glucocorticoides/administração & dosagem , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Metilprednisolona/administração & dosagem , Infecções Oportunistas/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Transplantados , Adulto , Idoso , Antivirais/efeitos adversos , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , China , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Transplante de Rim/mortalidade , Masculino , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Ventilação não Invasiva , Infecções Oportunistas/mortalidade , Infecções Oportunistas/terapia , Infecções Oportunistas/virologia , Oxigenoterapia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Eliminação de Partículas Virais , Adulto Jovem , Tratamento Farmacológico da COVID-19
15.
Transl Androl Urol ; 9(6): 2848-2854, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33457257

RESUMO

Recently, the mainstream curative treatment for primary hyperoxaluria type 1 (PH1) is combined liver and kidney transplantation, and only kidney transplantation is considered ineffective for most PH1 patients. Furthermore, vitamin B6 (B6) is the only permitted drug available for treatment. However, except for specific mutations such as G170R and F152I in gene AGXT, data of B6 effect on other mutations are lacking. Insufficient research has evaluated the efficacy of the combination of kidney transplantation and B6 treatment in the therapeutic strategy in PH1 patients. Here, we report a case of a 52-year-old male with frequent stone events and end-stage renal diseases (ESRD), and subsequently undergone kidney transplantation. Sudden rising of serum creatinine within two months after the transplantation. After gene sequencing, the mutations of A186V, R197Q, and I340M were presented in gene AGXT. Therefore, the patient was diagnosed with PH1. B6 administration was attempted during the period of waiting for liver transplantation. Four-week oral B6 therapy (50 mg tid) reduced the serum creatinine of the patient from 194 to 145 µmol/L, which revealed that the patient probably responded to B6 treatment. At the almost three-year follow-up, the patient's serum creatinine remained reduced (130 µmol/L), without urinary oxalate excretion. In this case, we established a positive effect, even a beneficial result, of the use of B6 as a retrospective therapeutic choice in PH1 treatment after kidney transplantation.

16.
Clin Exp Nephrol ; 23(7): 890-897, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30852714

RESUMO

BACKGROUND: Dysfunction of oxalate synthesis can cause calcium oxalate stone disease and inherited primary hyperoxaluria (PH) disorders. PH type I (PH1) is one of the most severe hyperoxaluria disorders, which results in urolithiasis, nephrocalcinosis, and end-stage renal disease. Here, we sought to determine the role of microRNAs in regulating AGXT to contribute to the pathogenesis of mutation-negative idiopathic oxalosis. METHODS: We conducted bioinformatics to search for microRNAs binding to AGXT, and examined the expression of the highest hit (miR-4660) in serum samples of patients with oxalosis, liver tissue samples, and determined the correlation and regulation between the microRNA and AGXT in vitro. RESULTS: MiR-4660 expression was downregulated in patients with oxalosis compared with healthy controls (84.03 copies/µL vs 33.02 copies/µL, P < 0.0001). Moreover, miR-4660 epigenetically decreased the expression of AGT in human liver tissues (Rho = - 0543, P = 0.037). Overexpression of miR-4660 in HepG2 and L02 cell lines led to dysregulation of AGXT at both the mRNA (by 71% and 81%, respectively; P < 0.001) and protein (by 49% and 42%, respectively; P < 0.0001) levels. We confirmed the direct target site of miR-4660 binding to the 3'UTR of AGXT by a luciferase assay. CONCLUSION: MiR-4660 is probably a new biomarker for mutation-negative idiopathic oxalosis by regulating the post-transcription of AGXT, providing a potential treatment target of mutation-negative idiopathic oxalosis.


Assuntos
Hepatócitos/enzimologia , Hiperoxalúria Primária/genética , MicroRNAs/genética , Transaminases/genética , Regiões 3' não Traduzidas , Sítios de Ligação , Estudos de Casos e Controles , Epigênese Genética , Regulação Enzimológica da Expressão Gênica , Marcadores Genéticos , Predisposição Genética para Doença , Células HeLa , Células Hep G2 , Humanos , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/enzimologia , MicroRNAs/metabolismo , Fenótipo , Transaminases/metabolismo
17.
Transplantation ; 103(11): 2388-2396, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30801522

RESUMO

BACKGROUND: Using pediatric donors for single-kidney transplantation (SKT) can increase the number of possible recipients. However, it is unclear when SKT involving small pediatric donors and adult recipients can safely be performed without compromising graft outcome. METHODS: From 2013 to 2017, a total of 102 SKTs in adult recipients were performed in our center using pediatric donors aged <12 years. We compared the outcomes from donors aged 8 to 36 months (the small-kidney group [SKG], n = 46) and from donors aged 3 to 12 years (the big-kidney group [BKG], n = 56). The median follow-up time was 30 months in the SKG and 28 months in the BKG. RESULTS: All patients achieved satisfactory renal function after transplantation, despite the fact that some patients (SKG, 19.6%; BKG, 28.6%) developed delayed graft function. One-year graft survival and death-censored graft survival in the SKG were 89.1% and 100%, respectively, comparable to the results in the BKG (92.9% and 98.2%). One year later, the graft and patient survival rates in both groups remained unchanged. Pulmonary infection was the main cause of death in patients with a functioning graft (SKG, 4 patients; BKG, 2 patients). Proteinuria occurred early in some patients (SKG, 30.4%; BKG, 19.6%) and decreased gradually within the first year posttransplantation. CONCLUSIONS: SKT from pediatric donors aged 8 to 36 months to selected adult recipients produced excellent intermediate-term outcomes, comparable with those when older pediatric donors were used. This study provides evidence to support a lower age limit for SKT from pediatric donors.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Função Retardada do Enxerto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Lactente , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Resultado do Tratamento , Adulto Jovem
18.
Int Immunopharmacol ; 67: 356-365, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30583234

RESUMO

Excessive activation of the TLR/MyD88 signaling pathway contributes to several inflammation-related diseases. Previously, our laboratory synthesized a novel thiazaol-aminoramification MyD88 inhibitor named TJ-M2010-5. In this study, we interrogated the role of MyD88, as well as the protective effect of TJ-M2010-5, in a d-gal/LPS-induced acute liver injury mouse model. In order to induce acute liver injury, BALB/c mice received intraperitoneal injection of d-gal and LPS at a dose of 800 mg/kg and 80 µg/kg body weight, respectively. All mice died within 48 h of injection without intervention. However, pre-treatment with TJ-M2010-5 as well as knock-out (KO) of the MyD88 gene significantly improved mouse survival rate to 73.3% and 80% at 48 h, respectively, and both treatments protected liver function. These pathological results demonstrated that TJ-M2010-5 and MyD88 KO reduced the infiltration of inflammatory cells and protected hepatocytes against apoptosis. Furthermore, TJ-M2010-5 remarkably inhibited NF-κB and MAPK signaling in vivo. LPS-induced activation of macrophages as well as pro-inflammatory factors were also shown to be decreased after TJ-M2010-5 treatment in vivo and in vitro. Taken together, these results suggested that blockage of the TLR/MyD88 signaling pathway by TJ-M2010-5 has an important role in the prevention of inflammation-related acute liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Galactosamina/toxicidade , Lipopolissacarídeos/toxicidade , Fator 88 de Diferenciação Mieloide/metabolismo , Piperazinas/farmacologia , Tiazóis/farmacologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Células de Kupffer/efeitos dos fármacos , Camundongos , Estrutura Molecular , Fator 88 de Diferenciação Mieloide/genética , Piperazinas/química , Tiazóis/química
19.
Curr Med Sci ; 38(5): 749-757, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30341509

RESUMO

Primary hyperoxaluria type 1 (PH1) is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT. Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian, especially in Chinese. To update the genotypes of PH1 in the Chinese population, we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center, five of whom had delayed diagnosis and failed in kidney transplantation. Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT. Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations. Furthermore, a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees. To the best of our knowledge, 2 novel variants of AGXT, p.Gly41Trp and p.Leu33Met, were first reported. Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT) at a protein level. The systematic review revealed significant population heterogeneity in PH1. In conclusion, new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore, a genotype-phenotype correlation is found in PH1.


Assuntos
Testes Genéticos , Hiperoxalúria Primária/genética , Transaminases/genética , Povo Asiático/genética , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Hiperoxalúria Primária/sangue , Hiperoxalúria Primária/patologia , Masculino , Mutação , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Transaminases/sangue , População Branca/genética
20.
J Viral Hepat ; 25(12): 1576-1581, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30009520

RESUMO

Due to the severe shortage of the donor pool in China, a large number of patients are waiting for a suitable liver, or even worse lose the opportunity of transplantation. Reasonable use of hepatitis B surface antigen-positive (HBsAg-positive) donors is one possible strategy to increase the donor pool but the long-term outcome in a Chinese population is unknown. To evaluate the safety of using of HBsAg-positive donor for liver transplantation, we set up a multicentric retrospective study from 1 January 2007 to 31 December 2012. A total of 8632 patients underwent liver transplantation during the period and 282 (2.97%) received a liver from a HBsAg-positive donor. A total of 259 cases in both the case and control groups were matched. The incidence of postoperative liver dysfunction, early-stage and long-term complications and the 1-, 3- and 5-year patient survival (78.92% vs 85.65%, 60.41% vs 69.14%, 58.08% vs 69.14%, respectively) showed no difference between the two groups (P value > 0.05). However, the 1-, 3- and 5-year HBV recurrence for patients received the HBsAg-positive donor was higher compared with controls (5.85% vs 1.97%, 11.63% vs 4.46%, 17.94% vs 4.46%, respectively, P value = 0.016). Our results showed the use of HBsAg-positive donors is feasible and postoperative antiviral therapy should be managed.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B/epidemiologia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Transplantados , Povo Asiático , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
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