RESUMEN
Early apoptosis of grafted islets is one of the main factors affecting the efficacy of islet transplantation. The combined transplantation of islet cells and bone marrow mesenchymal stem cells (BMSCs) can significantly improve the survival rate of grafted islets. Transcription factor insulin gene enhancer binding protein 1 (ISL1) is shown to promote the angiogenesis of grafted islets and the paracrine function of mesenchymal stem cells during the co-transplantation, yet the regulatory mechanism remains unclear. By using ISL1-overexpressing BMSCs and the subtherapeutic doses of islets for co-transplantation, we managed to reduce the apoptosis and improve the survival rate of the grafts. Our metabolomics and proteomics data suggested that ISL1 upregulates aniline (ANLN) and Inhibin beta A chain (INHBA), and stimulated the release of caffeine in the BMSCs. We then demonstrated that the upregulation of ANLN and INHBA was achieved by the binding of ISL1 to the promoter regions of the two genes. In addition, ISL1 could also promote BMSCs to release exosomes with high expression of ANLN, secrete INHBA and caffeine, and reduce streptozocin (STZ)-induced islets apoptosis. Thus, our study provides mechanical insight into the islet/BMSCs co-transplantation and paves the foundation for using conditioned medium to mimic the ISL1-overexpressing BMSCs co-transplantation.
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Exosomas , Insulinas , Islotes Pancreáticos , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Compuestos de Anilina/metabolismo , Apoptosis/genética , Cafeína/metabolismo , Cafeína/farmacología , Medios de Cultivo Condicionados , Subunidades beta de Inhibinas , Insulinas/metabolismo , Islotes Pancreáticos/metabolismo , Células Madre Mesenquimatosas/metabolismo , Estreptozocina/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Revascularization of the islet transplant is a crucial step that defines the success rate of patient recovery. Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported to promote revascularization; however, the underlying cellular mechanism remains unclear. Moreover, our liquid chromatography-tandem mass spectrometry results showed that BMSCs could promote the expression of insulin gene enhancer binding protein-1 (ISL1) in islets. ISL1 is involved in islets proliferation and plays a potential regulatory role in the revascularization of islets. This study identifies the ISL1 protein as a potential modulator in BMSCs-mediated revascularization of islet grafts. We demonstrated that the survival rate and insulin secretion of islets were increased in the presence of BMSCs, indicating that BMSCs promote islet revascularization in a coculture system and rat diabetes model. Interestingly, we also observed that the presence of BMSCs led to an increase in ISL1 and vascular endothelial growth factor A (VEGFA) expression in both islets and the INS-1 rat insulinoma cell line. In silico protein structure modeling indicated that ISL1 is a transcription factor that has four binding sites with VEGFA mRNA. Further results showed that overexpression of ISL1 increased both the abundance of VEGFA transcripts and protein accumulation, while inhibition of ISL1 decreased the abundance of VEGFA. Using a ChIP-qPCR assay, we demonstrated that direct molecular interactions between ISL1 and VEGFA occur in INS-1 cells. Together, these findings reveal that BMSCs promote the expression of ISL1 in islets and lead to an increase in VEGFA in islet grafts. Hence, ISL1 is a potential target to induce early revascularization in islet transplantation.
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Trasplante de Islotes Pancreáticos , Islotes Pancreáticos , Células Madre Mesenquimatosas , Animales , Médula Ósea/metabolismo , Humanos , Islotes Pancreáticos/metabolismo , Trasplante de Islotes Pancreáticos/métodos , Células Madre Mesenquimatosas/metabolismo , Ratas , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Delayed graft function (DGF) is an important complication of kidney transplantation and can be diagnosed according to different definitions. DGF has been suggested to be associated with the long-term outcome of kidney transplantation surgery. However, the best DGF definition for predicting renal transplant outcomes in Chinese donations after cardiac death (DCDs) remains to be determined. METHOD: A total of 372 DCD kidney transplant recipients from June 2013 to July 2017 in the First Affiliated Hospital of Xi'an Jiaotong University were included in this retrospective study to compare 6 different DGF definitions. The relationships of the DGF definitions with transplant outcome were analyzed, including graft loss (GL) and death-censored graft loss (death-censored GL). Renal function indicators, including one-year estimated glomerular filtration rate (eGFR) and three-year eGFR, and were compared between different DGF groups. RESULTS: The incidence of DGF varied from 4.19 to 35.22% according to the different DGF diagnoses. All DGF definitions were significantly associated with three-year GL as well as death-censored GL. DGF based on requirement of hemodialysis within the first week had the best predictive value for GL (AUC 0.77), and DGF based on sCr variation during the first 3 days post-transplant had the best predictive value for three-year death-censored GL (AUC 0.79). Combination of the 48-h sCr reduction ratio and classical DGF can improve the AUC for GL (AUC 0.85) as well as the predictive accuracy for death-censored GL (83.3%). CONCLUSION: DGF was an independent risk factor for poor transplant outcome. The combination of need for hemodialysis within the first week and the 48-h serum creatinine reduction rate has a better predictive value for patient and poor graft outcome.
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Funcionamiento Retardado del Injerto/diagnóstico , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Donantes de Tejidos , Adulto , Área Bajo la Curva , China , Creatinina/sangre , Funcionamiento Retardado del Injerto/epidemiología , Femenino , Tasa de Filtración Glomerular , Supervivencia de Injerto , Paro Cardíaco , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Incidencia , Estimación de Kaplan-Meier , Riñón/fisiología , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aims to investigate the regulatory mechanism of 1,25-(OH)2D3 on the proliferation of fibroblast-like synoviocytes (FLS) and expressions of pro-inflammatory cytokines in rheumatoid arthritis (RA) rats via microRNA-22 (miR-22). METHODS: A rat model of RA was established with a subcutaneous injection of type II collagen. After treated with different concentrations of 1,25-(OH)2D3 the proliferation of FLS was estimated by the MTT method, and the optimal concentration of 1,25-(OH)2D3 was selected for further experiments. Cell proliferation was detected by MTT. Cell cycle and apoptosis were analyzed by FCM. The IL-1ß, IL-6, IL-8, and PGE2 protein expressions were determined by ELISA, and MMP-3, INOS, and Cox-2 mRNA expressions were measured by qRT-PCR. RESULTS: The rat model of RA was successfully established. Compared with the blank group, the 1,25-(OH)2D3 and miR-22 inhibitors groups exhibited higher proliferation inhibition and apoptosis rates, lower levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, and PGE2), and decreased mRNA expressions of MMP-3, INOS, and Cox-2. The miR-22 mimics group had lower proliferation inhibition and apoptosis rates, elevated expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 than the blank group. In contrast to the 1,25-(OH)2D3 group, the proliferation inhibition and apoptosis rates were down-regulated, and the expressions of pro-inflammatory cytokines and MMP-3, INOS, and Cox-2 were up-regulated in the 1,25-(OH)2D3 + miR-22 mimics group. CONCLUSION: Our study demonstrated that 1,25-(OH)2D3 inhibits the proliferation of FLS and alleviates inflammatory response in RA rats by down-regulating miR-22.
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Artritis Reumatoide/patología , Colecalciferol/farmacología , Citocinas/análisis , MicroARNs/metabolismo , Animales , Antagomirs/metabolismo , Apoptosis , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Proliferación Celular , Células Cultivadas , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Masculino , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Ratas Sprague-Dawley , Sinoviocitos/citología , Sinoviocitos/patologíaRESUMEN
HLA-DPB1*1500:01N differs from HLA-DPB1*05:01:01:01 by one nucleotide in exon 3.
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Cadenas beta de HLA-DP , Nucleótidos , Humanos , Alelos , Secuencia de Bases , China , Análisis de Secuencia de ADNRESUMEN
The microbiome in a specific human organ has been well-studied, but few reports have investigated the multi-organ microbiome as a whole. Here, we aim to analyse the intra-individual inter-organ and intra-organ microbiome in deceased humans. We collected 1608 samples from 53 sites of 7 surface organs (oral cavity, esophagus, stomach, small intestine, appendix, large intestine and skin; n = 33 subjects) and performed microbiome profiling, including 16S full-length sequencing. Microbial diversity varied dramatically among organs, and core microbial species co-existed in different intra-individual organs. We deciphered microbial changes across distinct intra-organ sites, and identified signature microbes, their functional traits, and interactions specific to each site. We revealed significant microbial heterogeneity between paired mucosa-lumen samples of stomach, small intestine, and large intestine. Finally, we established the landscape of inter-organ relationships of microbes along the digestive tract. Therefore, we generate a catalogue of bacterial composition, diversity, interaction, functional traits, and bacterial translocation in human at inter-organ and intra-organ levels.
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Apéndice , Microbiota , Humanos , Traslocación Bacteriana , Estómago , Microbiota/genética , BocaRESUMEN
OBJECTIVE: To compare the clinical outcomes of open surgical peritoneal dialysis catheter (PDC) insertion with guide wire and the outcomes of PDC insertion without guide wire. METHODS: Data of the patients receiving open surgical Tenkchoff straight catheter insertion in our department from January 2005 to January 2011 were retrospectively analyzed. The 117 patients in whom PDC insertion was conducted with the guidance of guide wire were enrolled into group A, and the 121 cases receiving PDC insertion without guide wire were enrolled into group B. The incidences of post-operative complications (catheter obstruction, catheter displacement, bloody dialysate, and dialysate leakage), catheter survival, and patient survival rates were compared between the 2 groups. RESULTS: The baseline characteristics (gender, age, body mass index, prothrombin time, activated partial thromboplastin time, platelet count, serum creatinine, follow-up time, primary diseases, and outcomes) of the 2 groups were comparable (all P>0.05). In post-operative complications, only the incidence of early bloody dialysate showed significant difference, being 16.2% in group A and 7.4% in group B (P=0.04). Catheter and patient survival rates were not significantly different between the two groups. Overweight patients showed a higher incidence of catheter obstruction compared with normal weight patients [16.0% (4/25) vs.3.3% (7/213), P=0.02], but no differences in post-operative complications were found among overweight patients between the 2 groups. CONCLUSIONS: Open surgical Tenkchoff straight catheter insertion without guide wire does not lead to higher risk of post-operative complications and catheter removal. It may be an alternative option when guide wire is not available.
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Cateterismo/instrumentación , Diálisis Peritoneal/instrumentación , Adulto , Anciano , Cateterismo/efectos adversos , Cateterismo/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Diálisis Peritoneal/mortalidad , Complicaciones Posoperatorias/etiologíaRESUMEN
Reduced Na+/K+-ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of renal diseases. NKA-mediated Src activation is not the only reason for NKA-related renal fibrosis. In this study, we found that genetic reduction of NKAα1 exhibited exacerbated tubulointerstitial lesions and fibrosis in the UUO mice model. Activation of NKAα1 with an antibody against the extracellular DR region of the NKAα1 subunit (DRm217) prevented UUO-induced tubulointerstitial lesions, preserved kidney function, and decrease renal fibrosis. Further studies revealed that NKAα1 deficiency mice exhibited high inflammation factors expression when they suffered UUO surgery, compared with NKAα1+/+ (WT) mice. DRm217 alleviated inflammatory cell infiltration, suppress NF-κB phosphorylation, and decreased inflammatory factors expression in the UUO mice model. Released HMGB1 can trigger the inflammatory response and contribute to renal fibrosis. Knockdown of NKA in renal tubular cells or in NKAα1+/- mice was associated with more susceptibility to HMGB1 release in the UUO mice model. DRm217 exerted its antifibrotic effect via inhibiting HMGB1 release. Furthermore, AMPK activation participates in the effect of DRm217 on inhibiting HMGB1 release. Our findings suggest that NKAα1 is a regulator of renal fibrosis and its DR-region is a novel target on it.
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Proteína HMGB1 , Enfermedades Renales , Obstrucción Ureteral , Ratones , Animales , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Riñón/patología , Enfermedades Renales/patología , Anticuerpos Monoclonales/farmacología , FibrosisRESUMEN
Activation of NF-κB pathway and co-stimulatory system CD40/CD40L promotes the inflammation, which plays a key role in the failure of islet graft. Therefore, the purpose of this study was to determine if simultaneous blockade of CD40/CD40L and IκB/NF-κB pathways could protect islet graft. Streptozocin-induced diabetic Wistar rats were transplanted intraportally with 2000 IEQ islets isolated from Sprague-Dawley rats. The rats were divided into five groups: nontreatment group, AdGFP-treated group, Ad-IκBα-treated group, Ad-sCD40LIg-treated group, and Ad-IκBα-IRES(2) -sCD40L-treated group. The islet graft mean survival time (MST), insulin expression of islet grafts, and the levels of cytokines in peripheral blood, were measured for the animals in each group. Our study confirmed that islet cells transfected with low doses of adenovirus could achieve high transfection efficiency, and would not affect the function of islet cells (P > 0.05). Splenocytes cultured with Ad-IκBα-IRES2-CD40L-transfected islets resulted in homospecific hyporesponsiveness. The islet graft MST (>100 d) in the Ad-IκBα-IRES2-sCD40L-treated group was dramatically prolonged compared with that in the nontreatment group (7.1 ± 1.16 d). In addition, TNF-α, IL-1ß, and IFN-γ were diminished in the Ad-IκBα-IRES2-sCD40L-treated group, which was commensurate with the reduced cellular infiltration (P < 0.01). Simultaneous blockade of the CD40/CD40L and IκB/NF-κB pathways could effectively extend the survival of islet grafts.
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Antígenos CD40/biosíntesis , Ligando de CD40/biosíntesis , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/citología , FN-kappa B/metabolismo , Animales , Línea Celular , Citocinas/biosíntesis , Diabetes Mellitus Experimental , Supervivencia de Injerto , Humanos , Masculino , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Bazo/citología , Estreptozocina/farmacología , Factores de TiempoRESUMEN
Bone marrow mesenchymal stem cells (BMSCs) can be induced to differentiate into neuron-like cells under appropriate conditions often involving toxic reagents that are not applicable for clinical transplantation. The present study investigated whether tea polyphenol (TP), a native nontoxic antioxidant, could induce mouse neuron-like cell differentiation of BMSCs in vitro. BMSCs, dissected from mouse femur bone marrow, were amplified in culture and treated with TP or beta-mercaptoethanol (BME, control). Morphological changes were observed under light microscopy. After 12 h treatment with 50 microg/ml TP or 5 mM BME, most cells differentiated into neuron-like cells exhibiting neuronal morphological characteristics, cellular shrinkage and neurite growth. Immunocytochemistry and reverse transcription (RT)-PCR results demonstrated neuronal marker expression in the induced cells with no glial fibrillary acidic protein expression. Taken together, TP induced mouse BMSCs to differentiate into neuron-like cells in vitro. These findings provide a potential source for the treatment of various neurological diseases.
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Catequina/análogos & derivados , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Neuronas/citología , Té/química , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/fisiología , Catequina/farmacología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Expresión Génica/efectos de los fármacos , Células Madre Mesenquimatosas/fisiología , Ratones , Ratones Endogámicos BALB C , Neuronas/fisiología , Fármacos Neuroprotectores/farmacologíaRESUMEN
BACKGROUND: The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation. METHODS: This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses. RESULTS: In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs (Pâ<â0.001), glomerulitis (Pâ<â0.001), peritubular capillaritis (Pâ<â0.001), and human leukocyte antigen (HLA) B eplet MM (Pâ=â0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742-33.668, Pâ<â0.001), glomerulitis (OR: 3.581, 95%CI: 1.246-10.289, Pâ=â0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005-1.353, Pâ=â0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy. CONCLUSIONS: PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.
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Trasplante de Riñón , Aloinjertos , Biopsia , Complemento C4b , Rechazo de Injerto , Antígenos HLA , Antígenos HLA-B , Humanos , Trasplante de Riñón/efectos adversos , Fragmentos de Péptidos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: to study the relationship between the expression of serum human leucocyte antigen-G5 (HLA-G5)/soluble CD30 (sCD30) and the function of renal graft in kidney transplant recipients and investigate the immune status of recipients with combined HLA-G5 and sCD30. METHODS: from January 2002 to November 2008, a total of 66 kidney transplant recipients in our centre were selected as subjects and divided into three groups: stable function of renal graft (n = 38), acute rejection (n = 15) and chronic rejection (n = 13). The expressions of serum HLA-G5 and sCD30 were detected. There were two different immune conditions with acute/chronic allograft rejection and normal renal graft in kidney transplant recipients as evaluated by combined HLA-G5 and sCD30. The sensitivity, specificity and critical value of the method were analyzed by the curve of receiver operating characteristic. RESULTS: the levels of HLA-G5 and sCD30 were significantly correlated with serum creatinine (r = -0.493, 0.691, both P < 0.01). Within the first year post-transplantation, the sensitivity was 78.6% and the specificity 85.7% when HLA-G5 critical value 82 microg/L and sCD30 critical value 12.2 microg/L. After one year post-transplantation: the sensitivity was 92.3% and the specificity 84.6% when HLA-G5 critical value 141 microg/L and sCD30 critical value 10.3 microg/L. CONCLUSION: the immune state of recipients are evaluated by combine HLA-G5 and sCD30 which may be a simple and valid method.
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Rechazo de Injerto/inmunología , Antígenos HLA/sangre , Antígenos de Histocompatibilidad Clase I/sangre , Antígeno Ki-1/sangre , Trasplante de Riñón/inmunología , Adulto , Anciano , Femenino , Antígenos HLA/inmunología , Antígenos HLA-G , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Antígeno Ki-1/inmunología , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto JovenRESUMEN
OBJECTIVE: To study the effect of Poria cocos (Pcs) in preventing acute rejection of rats after renal transplantation and its mechanism. METHODS: Rat orthotopic renal transplantation model was performed with Wistar rat as donor and SD rat as donee. All donees were divided into 4 groups, 10 in each group, before transplantation. They were treated respectively with normal saline 5 mL x kg(-1) x d(-1) (A), Pcs 25 mg x kg(-1) x d(-1) (B), Pcs 50 mg x kg(-1) x d(-1) (C) and ciclosporin A (CsA) 5 mg x kg(-1) x d(-1) (D) by intragastric administration. The renal allograft survival time (ST) was recorded, and the serum levels of creatinine (SCr), interleukin-2 (IL-2), gamma-interferon (gamma-IFN), CD4+, CD8+ lymphocytes percentage, CD4+/CD8+ ratio, as well as the pathologic changes were observed one week after transplantation. RESULTS: ST of the renal graft in Groups C and D was significantly longer with pathologic change evidently less than those in Groups A and B (P<0.01), and the ST in Group C was shorter that in Group D (P<0.05). Changes of renal function and urine volume were identified to the pathological change of graft, the initiating time of renal dysfunction was later in Groups C and D than that in Groups A and B. Serum levels of IL-2, IFN-gamma and CD4+ percentage in Group C were significantly lower than those in Groups A and B, but higher than those in Group D respectively (P<0.05 or P<0.01), while CD8+ percentage in Group C was significantly lower than that in Group A (P<0.05), but insignificantly different to that in Groups B and D (P>0.05). CONCLUSION: Pcs shows good dosage-dependent effect in suppressing acute rejection of renal transplantation, but the effect is inferior to that of CsA.
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Rechazo de Injerto/prevención & control , Trasplante de Riñón , Materia Medica/uso terapéutico , Poria/química , Animales , Ciclosporina/uso terapéutico , Masculino , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
Proteasome inhibitor bortezomib offers one more option for acute or chronic antibody-mediated rejection after kidney transplantation, but aggravated acute kidney injury (AKI) in some cases early after surgery using bortezomib bring new problem. Here, we evaluated the effects of bortezomib and ONX-0914 on renal tubule injury in a mouse model of ischemia-reperfusion injury. After treated with bortezomib, serum creatinine, usea nitrogen and tubular necrosis significantly increased compared with vehicle-treated mice, but decreased in ONX-0914 group mildly. Infiltration of neutrophil and macrophage were less in bortezomib and ONX-0914-treated mice than vehicle-treated group, and the same was observed on oxidative stress in the kidneys. Furthermore, the apoptosis of renal tubular epithelial cells increased in bortezomib-treated mice' kidneys compared with ONX-0914 and vehicle-treated controls. In vitro HK2 cell experiments also demonstrated the proapoptotic effect of bortezomib. The mRNA expression of several proapoptotic factors increased in kidneys of bortezomib-treated mice. In brief, bortezomib, as a proteasome inhibitor, shows a certain cytotoxicity to renal tubular epithelial cell during ischemia/reperfusion injury (IRI) through increased apoptosis. ONX-0914, as an immunoproteasome inhibitor, showed equal potency on anti-inflammation and oxidative stress relieving compared with bortezomib, while less cytotoxicity. The results render the immunoproteasome is a better target for anti-rejection and protecting kidney function in the field of organ transplantation.
RESUMEN
BACKGROUND: Kidney transplant is always emergent operations and frequently need to be performed at nighttime to reduce cold ischemia time (CIT). Previous studies have revealed that fatigue and sleep deprivation can result in adverse consequences of medical procedures. This study aimed to evaluate whether nighttime operation has adverse impact on kidney transplant. METHODS: A retrospective analysis of recipients accepted kidney transplant from deceased donors in one center from 2014 to 2016 was performed. Daytime transplant was defined as operation started after 8 AM or ended before 8 PM and nighttime operation was defined as operation ended after 8 PM or started before 8 AM. The incidences of complications such as delayed graft function, acute rejection, surgical complications and nosocomial infections were compared between 2 groups. Student's t-test was used to analyze continuous variables such as serum creatinine (Scr) at 1-year of post-transplant. The Chi-square test was used to analyze categorical variables. Differences in recipients and graft survival were analyzed using Kaplan-Meier methodology and log-rank tests. RESULTS: Among the 443 recipients, 233 (52.6%) were classified into the daytime group and the others 210 (47.4%) were in the nighttime group. The 1-year survival rate of recipients was similar for the recipients in the daytime and nighttime groups (95.3% vs. 95.2%, Pâ=â0.981). Although the 1-year graft survival rate in the nighttime group was slightly superior to that in the daytime group, the difference was not significant (92.4% vs. 88.4%, Pâ=â0.164). Furthermore, Scr and incidence of complications were also not significantly different between the 2 groups. CONCLUSIONS: Our results suggested that operation time of kidney transplant with short CIT has no significant impact on the outcome of kidney transplant. Nighttime operation of kidney transplant with short CIT could be postponed to the following day to alleviate the burden on medical staffs and avoid the potential risk.
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Trasplante de Riñón/mortalidad , Adulto , Cadáver , Isquemia Fría , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
B cell activating factor (BAFF) belonging to TNF family is a cytokine that enhances B-cell proliferation and differentiation. Recently, It has been suggested that BAFF might be a potential therapeutic target for treating autoimmune disease. However, the relationship between BAFF and allograft rejection is controversial, and the clinical significance of BAFF in predicting allograft rejection need to be further explored. We conducted 6-month follow-up study to confirm the hypothesis that BAFF might be a risk factor for predicting acute rejection in kidney transplant recipients. At the end of the study, a total of 155 kidney transplant recipients were recruited from October 2015 to October 2017, and classified into acute rejection group (n = 34) and stable renal function group (n = 121) according to their clinical course. We demonstrate that the serum BAFF levels when acute rejection occurred was significantly higher than that in the stable renal function group (2426.19 ± 892.19 vs. 988.17 ± 485.63 pg/mL, P < 0.05). BAFF expression was significantly enhanced in the membrane and cytoplasm of renal tubule epithelial cells in the transplant kidney tissue with acute rejection, and a positive correlation between BAFF and C4d expression was also observed (r = 0.880, P = 0.001). ROC analyses highlight the superiority of serum BAFF level before transplant over those on other post-transplant days in prediction of acute rejection episodes. The sensitivity, specificity and AUC (area under curve) were 83.3, 89.5, and 0.886%, respectively. Kaplan-Meier survival analysis showed that recipients with higher pretransplant BAFF levels had higher acute rejection incidence (P = 0.003). In conclusion, we have identified that BAFF levels are associated with the acute rejection and could be a promising biomarker to predict kidney transplant rejection risks.
Asunto(s)
Factor Activador de Células B/sangre , Rechazo de Injerto/sangre , Rechazo de Injerto/epidemiología , Trasplante de Riñón/efectos adversos , Adulto , Biomarcadores/sangre , Complemento C4b/metabolismo , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/metabolismo , Periodo Preoperatorio , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Receptores de Trasplantes , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the efficacy of kushenin in treating patients with chronic hepatitis C after renal transplantation. METHODS: Fifty-five patients were randomly assigned by lottery to the treatment group (29 cases) and control group (26 cases). The same immunosuppression therapy was given to all patients in both groups. Patients in the treatment group were treated with kushenin 0.6 g once a day, while those in the control group were treated with conventional liver protective agents such as vitamins. The treatment duration of both groups was 3 months. The incidences of serious hepatitis and acute rejection reaction, serum biochemistry parameters including indicators of liver and kidney functions, hepatic fibrosis index, and serum HCV-RNA were compared between the two groups. RESULTS: (1) The incidence of serious hepatitis in the treatment group and the control group was 3.45% (1/29 cases) and 11.54% (3/26 cases), respectively, which was insignificantly different between the two groups (P=0.335). (2) The incidence of acute rejection in the treatment group was 6.90% (2/29 cases) and that in the control group was 7.69% (2/26 cases), showing insignificant difference (P=0.335). (3) The differences in serum alanine aminotransferase (ALT), direct bilirubin (DBIL), hyaluronic acid (HA), propeptide collagen type III (PC III), laminin (LN), collagen type IV (Col IV) levels between the two groups were insignificant before transplantation (P>0.05), while the above-mentioned parameters in the treatment group were significantly lower than those in the control group after transplantation (P<0.05). The difference in serum creatinine (SCr) and endogenous creatinine clearance rate (CCr) between the two groups was insignificant before and after transplantation (P>0.05). (4) The negative conversion rate of HCV-RNA in the treatment group was 31.03% (9/29 cases), significantly higher than the value of 11.54% (3/26 cases) in the control group after transplantation (P<0.05). (5) The levels of serum ALT and DBIL in patients with HCV-RNA converted to negative were significantly lower than those with still-positive HCV-RNA (P<0.05). CONCLUSIONS: Kushenin has a certain effect on inhibiting the proliferation of HCV, protecting liver cells, and anti-liver fibrosis. On the other hand, it has no obvious influence on renal allograft function. Thus, the drug is clinically safe and effective for use in treating patients with chronic hepatitis C after renal transplantation.
Asunto(s)
Antivirales/administración & dosificación , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/etiología , Trasplante de Riñón/efectos adversos , Pterocarpanos/administración & dosificación , Pterocarpanos/uso terapéutico , Adolescente , Adulto , Antivirales/efectos adversos , China/epidemiología , Femenino , Rechazo de Injerto , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/fisiopatología , Humanos , Incidencia , Pruebas de Función Renal , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Pruebas de Función Hepática , Masculino , Pterocarpanos/efectos adversos , ARN Viral/sangreRESUMEN
Arctigenin (ATG) is one of the main active substances in fruit derived from Arctium lappa L. Previous studies have reported that ATG have antitumor, neuroprotective, antioxidant, antifibrosis and anti-inflammatory functions. However, the actions of ATG in kidney with acute injury following ischemia/ reperfusion (I/R) is still uncertain. In our study, mice were subjected to kidney I/R by having the kidney pedicles clamped and administered with vehicle or ATG (1, 3 or 9â¯mg/kg/d) via oral gavage for 7 consecutive days prior to I/R. Notably, ATG aggravated kidney I/R injury with the concentration increases. Multiple biochemical assays and histological examination showed ATG significantly alleviated the inflammatory response as reflected by a decreased expression of proinflammatory cytokine, TLR4/MyD88, and NF-κB, along with the infiltration of CD68+ macrophage and CD11b+Gr1+ neutrophil in the kidneys. Meanwhile, ATG alleviated I/R-induced oxidative stress proved by increasing kidney manganese superoxide dismutase and glutathione peroxidase activity but reducing levels of malonaldehyde and inducible nitric oxide synthase. On the contrary, apoptosis was significantly increased in kidneys of ATG-treated mice compared with vehicle-treated controls, especially in tubular cells. There were increased numbers of TUNEL positive cells and increased Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9 expression. The current study demonstrates that pretreatment of ATG aggravates I/R induced acute kidney injury by increasing apoptosis of tubular cells despite reducing infiltrating inflammatory cells and proinflammatory cytokine.
Asunto(s)
Lesión Renal Aguda/prevención & control , Antiinflamatorios/uso terapéutico , Apoptosis/efectos de los fármacos , Furanos/uso terapéutico , Riñón/efectos de los fármacos , Lignanos/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Furanos/administración & dosificación , Furanos/efectos adversos , Inflamación , Riñón/inmunología , Riñón/metabolismo , Riñón/patología , Lignanos/administración & dosificación , Lignanos/efectos adversos , Masculino , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/complicaciones , Daño por Reperfusión/patologíaRESUMEN
NLRC5, as the largest member of nucleotide-binding domain and leucine-rich repeat (NLR) family, was involved in various physiological processes, such as inflammation, fibrosis, innate immunity and diabetic nephropathy. However, the role of NLRC5 in acute kidney injury remains unclear. The aim of this study was to investigate the role of NLRC5 in human renal proximal tubular epithelial cells (HK-2) exposed to hypoxia/reoxygenation (H/R). Our results demonstrated that the expression of NLRC5 was significantly up-regulated in HK-2 cells exposed to H/R. Knockdown of NLRC5 significantly improved the viability of HK-2 cells exposed to H/R. In addition, knockdown of NLRC5 efficiently inhibited H/R-induced oxidative stress and apoptosis in HK-2 cells. Mechanistically, knockdown of NLRC5 markedly enhanced the activation of PIK3/Akt signaling pathway in H/R-stimulated HK-2 cells. In summary, our findings indicate that knockdown of NLRC5 attenuates renal I/R injury in vitro through the activation of PI3K/Akt signaling pathway.