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The optical properties of deep-ultraviolet (DUV) light-emitting diode (LED) with Al nanograting structure are investigated by three-dimensional (3D) finite-difference time-domain (FDTD) simulation. The peak intensity of TE and TM polarization radiation recombination rate of the grating structure is increased by 33.3% and 22.0% as compared to the control structure with Al plane. The light extraction efficiency (LEE) of the emitted light whose propagation direction is in the plane perpendicular to the Al-grating ridge is much higher than that in the plane parallel to the Al-grating ridge due to the scattering of the grating. Without considering the lateral surface extraction and packaging, the total LEE of the grating structure can be improved by 41.4% as compared to the control structure. The peak intensity of the output spectrum of the DUV LED with the grating structure can be increased by 70.3%.
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BACKGROUND: Preservation fluid (PF) contamination, especially by multidrug-resistant (MDR) Gram-negative bacteria (GNB), poses a high risk of donor-derived infection (DDI) and severe clinical outcomes. We sought to determine whether the use of colistin sulfate to decontaminate PF in kidney transplantation can decrease the incidence of probable DDI (p-DDI) caused by MDR GNB. METHODS: In a retrospective study of 916 recipients who received deceased donation, 864 PF samples were collected and cultured, and microbiological contaminants were recorded with the recipients' clinical data and outcomes. From March 2016 to May 2019, 624 samples were decontaminated with ceftizoxime, and from June 2019 to March 2021, 240 samples were decontaminated with colistin sulfate. Between-group comparisons were performed to assess the ability of the two decontamination regimens to decrease the incidence of p-DDI, especially MDR GNB-related infection. RESULTS: The overall PF contamination rate was 54.51% (471/864), and 80 samples were positive for MDR GNB contamination. All p-DDIs occurred in the ceftizoxime group (p < 0.001), and 67.65% of p-DDIs were MDR GNB-related. In the ceftizoxime group, 23 of 61 cases of MDR GNB contamination led to related p-DDIs, while none occurred in the colistin sulfate group (p = 0.002). Among the 23 patients with p-DDIs, 5 died due to severe infection, and 2 experienced graft loss. CONCLUSIONS: The goal of decontamination should be to decrease the risk of MDR GNB-related p-DDI, and colistin sulfate could be an effective and feasible option.
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Infecções por Bactérias Gram-Negativas , Transplante de Rim , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftizoxima/farmacologia , Colistina/uso terapêutico , Descontaminação , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Humanos , Incidência , Transplante de Rim/efeitos adversos , Estudos RetrospectivosRESUMO
Renal ischaemia-reperfusion (IR) is a major cause of acute kidney injury (AKI). Cold-inducible RNA-binding protein (CIRBP) may contribute to AKI because its deficiency protects against renal IR injury in a mechanism believed to involve ferroptosis. We aimed to investigate whether ferroptosis is associated with CIRBP-mediated renal damage. The differential expression of CIRBP was examined in tubular epithelial (HK2) cells during hypoxia-reoxygenation (HR) or in response to erastin, an inducer of ferroptosis. CIRBP expression was increased in response to HR or erastin in HK2 cells but the silencing of CIRBP inhibited HR and erastin-induced ferroptosis together with ferritinophagy. We discovered an interaction between CIRBP and ELAVL1 using STRING software, which was verified through co-immunoprecipitation and fluorescence colocalization assays. We found that ELAVL1 is a critical regulator in the activation of ferritinophagy and the promotion of ferroptosis. HR or erastin also induced the expression of ELAVL1. An autophagy inhibitor (hydroxychloroquine) or si-ELAVL1 transfection reversed CIRBP-enhanced ferritinophagy activation and ferroptosis in HK2 cells under HR. Injection of anti-CIRBP antibody into a mouse model of IR inhibited ferroptosis and decreased renal IR injury in vivo. In summary, our results provide evidence that ferritinophagy-mediated ferroptosis could be responsible for CIRBP-enhanced renal IR injury.
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BACKGROUND: The International Pediatric Nephrology Association (IPNA) Global Kidney Replacement Therapy (KRT) Registry was established to evaluate the incidence and outcomes of kidney replacement therapy (dialysis and transplantation) provided to children worldwide. Analysis of registry data for separate regions is feasible. METHODS: Three centers located in Shanghai, Guangzhou, and Zhengzhou, which have the greatest number of pediatric kidney transplantation cases in China, participated in this analysis of transplant data. Data were registered by each center for patients under the age of 19 years who received a single-organ kidney transplant for the first time between 2011 and 2018. RESULTS: In total, 415 patients (59.8% male) aged 1.4-18.7 (median 12.1) years were followed for 0.3-97.1 (median 27.7) months. The number of kidney transplants increased from a total of 129 during 2011-2014 to 286 cases during 2015-2018. 85.8% of patients received the transplanted kidney from a pediatric (age < 19 years) donor, and deceased donors accounted for 94% of all donors. 8.0% of grafts were lost. One and 5-year patient survival rates were 97.6% and 95.5%, respectively. The major cause of death was infection (7/14). Similar graft and patient survival rates were observed for organs from pediatric and adult donors in 6-11 and 12-18 year recipient age groups, whereas recipients < 6 years showed inferior patient and graft survival. CONCLUSIONS: Pediatric kidney transplantation shows favorable short-term and medium-term outcomes in China. Our experience supports use of pediatric donors in pediatric kidney transplantation, but attention directed to the outcome of recipients aged under 6 is necessary. Graphical abstract.
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Transplante de Rim , Adolescente , Criança , China/epidemiologia , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Nefrologia , Sistema de Registros , Diálise Renal , Doadores de Tecidos , Resultado do Tratamento , Adulto JovemRESUMO
Apoptosis of tubular epithelium cells (TECs) plays critical roles in renal ischemia reperfusion (I/R) injury, but the molecular regulatory mechanisms of apoptosis still require further investigation. Recently, phosphatase family members have been suggested to regulate multiple aspects of the injury and regeneration response. However, the roles of SHP-1, an important protein-tyrosine phosphatase, in the regulation of renal I/R injury remain unknown. Here, we found that SHP-1 knockdown in vivo significantly increased renal I/R injury and aggravated the apoptosis of TECs. Consistently, after SHP-1 knockdown in TECs in vitro, a sharp increase of apoptosis induced by cobalt dichloride was found. The protective role of SHP-1 was also validated in a TEC cell line stably overexpressing SHP-1. Mechanistically, the ASK1/MKK4/JNK pro-apoptosis signal was over activated after SHP-1 knockdown, and SHP-1 could bind to and dephosphorylate ASK1 to inhibit its activation, thus repressing apoptosis.
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MAP Quinase Quinase Quinase 5/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Insuficiência Renal/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Apoptose , Células HEK293 , Humanos , Rim/metabolismo , Rim/patologia , Camundongos Endogâmicos C57BL , Fosforilação , Insuficiência Renal/patologia , Traumatismo por Reperfusão/patologia , Transdução de SinaisRESUMO
For the [0001] oriented AlGaN-based deep ultraviolet light-emitting diodes (DUV LEDs), the holes in the p-type electron blocking layer (p-EBL) are depleted due to the polarization induced positive sheet charges at the last quantum barrier (LQB)/p-EBL interface. The hole depletion effect significantly reduces the hole injection capability across the p-EBL. In this work, we propose inserting a thin AlN layer between the LQB and the p-EBL, which can generate the hole accumulation at the AlN/p-EBL interface. Meanwhile, the holes can obtain the energy when traveling from the p-EBL into the multiple quantum wells (MQWs) by intraband tunneling through the thin AlN layer. As a result, the hole injection and the external quantum efficiency (EQE) have been remarkably enhanced. Moreover, we point out that the thick AlN insertion layer can further generate the hole accumulation in the p-EBL and increase the hole energy which helps to increase the hole injection. We also prove that the intraband tunneling for holes across the thick AlN insertion layer is facilitated by using the optimized structure.
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RTx is currently the best treatment for children with ESRD. This study retrospectively analyzed the outcomes of growth after RTx using the pediatric-to-pediatric allocation strategy and some factors that may affect it. From March 2012 to August 2016, 8 en bloc and 38 single pediatric RTxs were performed at our center using organs from small pediatric deceased donors (weight < 15 kg). Growth before and after RTx was analyzed according to the height-for-age z-score at RTx, the 3-year follow-up, and adulthood and compared between the procedures. The chi-square test and multiple linear regression analysis were used for statistical analyses. Overall, 79.2% of children were diagnosed with chronic nephritis before RTx; 14.6% of cases were due to congenital urinary tract malformation, and 6.3% of cases were due to unknown causes. All grafts and patients survived postoperatively. The mean estimated GFRs were 92.7 ± 28.6 mL/min/1.73 m2 , 100.9 ± 32.3 mL/min/1.73 m2 , and 110.1 ± 34.8 mL/min/1.73 m2 at 1, 2, and 3 years' postoperatively, respectively. The children's postoperative growth and development, particularly during the first year postoperatively, improved but were negatively correlated with age and the height-for-age z-score before RTx. The growth of children after RTx was moderate and accelerated during prepubescence. The rate of post-RTx growth during the first year postoperatively was unrelated to the recipient's sex or duration of dialysis (P > 0.05) but was negatively correlated with age at RTx (r = -0.349, P = 0.043). Future studies on the long-term outcomes are still needed.
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Estatura , Peso Corporal , Seleção do Doador/métodos , Transtornos do Crescimento/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/epidemiologia , Humanos , Modelos Lineares , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Resultado do Tratamento , Adulto JovemRESUMO
Bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) is a classical morphogen; a molecule that acts at a distance and whose concentration influences cell proliferation, differentiation, and apoptosis. Key events requiring precise Bmp2 regulation include heart specification and morphogenesis and neural development. In mesenchymal cells, the concentration of BMP2 influences myogenesis, adipogenesis, chondrogenesis, and osteogenesis. Because the amount, timing, and location of BMP2 synthesis influence pattern formation and organogenesis, the mechanisms that regulate Bmp2 are crucial. A sequence within the 3'UTR of the Bmp2 mRNA termed the "ultra-conserved sequence" (UCS) has been largely unchanged since fishes and mammals diverged. Cre-lox mediated deletion of the UCS in a reporter transgene revealed that the UCS may repress Bmp2 in proepicardium, epicardium, and epicardium-derived cells (EPDC) and in tissues with known epicardial contributions (coronary vessels and valves). The UCS also repressed the transgene in the aorta, outlet septum, posterior cardiac plexus, cardiac and extra-cardiac nerves, and neural ganglia. We used homologous recombination and conditional deletion to generate three new alleles in which the Bmp2 3'UTR was altered as follows: a UCS flanked by loxP sites with or without a neomycin resistance targeting vector, or a deleted UCS. Deletion of the UCS was associated with elevated Bmp2 mRNA and BMP signaling levels, reduced fitness, and embryonic malformations.
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Regiões 3' não Traduzidas , Proteína Morfogenética Óssea 2/genética , Pericárdio/metabolismo , Animais , Proteína Morfogenética Óssea 2/metabolismo , Sequência Conservada , Vasos Coronários/embriologia , Vasos Coronários/metabolismo , Deleção de Genes , Camundongos , Camundongos Endogâmicos C57BL , Pericárdio/embriologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Interleukin-22 (IL-22) is an inflammatory cytokine mainly produced by activated Th17 and Th22 cells. The data presented here demonstrate that IL-22 induced the migration and invasion of papillary thyroid cancer (PTC) cells. MicroRNA expression analysis and functional studies indicated that IL-22-mediated migration and invasion is positively regulated by miR-595. Further mechanistic studies revealed that sex-determining region Y-box 17 (Sox17) is directly targeted by miR-595. We then demonstrated that IL-22 regulated migration and invasion of PTC cells via inhibiting Sox17 expression. Interestingly, in PTC cell lines and PTC tissues, expression of IL-22 and miR-595 was upregulated and Sox17 downregulated compared with normal thyroid, and their expression levels were closely correlated. Taken together, this present study suggests that IL-22 stimulation enhances the migration and invasion of PTC cells by regulating miR-595 and its target Sox17.
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Carcinoma/patologia , Interleucinas/farmacologia , MicroRNAs/fisiologia , Fatores de Transcrição SOXF/fisiologia , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Invasividade Neoplásica , Fatores de Transcrição SOXF/genética , Câncer Papilífero da Tireoide , Interleucina 22RESUMO
Currently, most kidneys from small pediatric deceased donors are transplanted into adult recipients (i.e., PTA). However, due to the weight mismatch, there is a high discard rate and a high ratio of EBKTs if adopting PTA. Here, we sought both to optimize utilization of these challenging but scarce donor grafts by selecting pediatric recipients and to characterize the feasibility and efficacy of this PTP allocation strategy. From February 2012 to October 2014, kidneys from 27 infant donors ≤ 15 kg were procured and distributed to 38 pediatric candidates in our center. The grafts were utilized for EBKT if the donor weighed 2.5-5 kg and for SKT if the donor weighed 5-15 kg, leading to 10 EBKTs and 28 SKTs. The overall utilization rate from small pediatric deceased donors was 94.12%. After a follow-up of 3-26 months, the graft survival rate was 89.47%, with four graft losses due to vascular thrombosis. Kidneys from low-body-weight donors should be applied to pediatric recipients, and the kidneys from infant donors ≥ 5 kg can be used in single-kidney-transplant procedures at experienced centers to optimize utilization.
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Sobrevivência de Enxerto , Transplante de Rim , Tamanho do Órgão , Insuficiência Renal/cirurgia , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Peso Corporal , Criança , Pré-Escolar , Morte , Feminino , Seguimentos , Rejeição de Enxerto , Humanos , Lactente , Isquemia , Masculino , Pediatria , Trombose/etiologiaRESUMO
The organ donation system in China has far lagged behind international levels. Transformation of this situation began in July 2005. A complete organ donation system that ensures fairness, impartiality, transparency, and respect for life has now been developed. This system is composed of regulations and policies, an organizational structure, operational guidelines, organ procurement organizations, registration of donors and recipients, and an organ allocation system. Since March 2010, pilot trials on donation after circulatory death (DCD) have been carried out. In 4 years, organ donation has started in 25 of 32 provinces in the country. From 2010 to 2013, the ratio of DCD liver transplantation to total case numbers in China rose from 1.38% to 26.1%, whereas for kidney, the ratio were 0.59% and 24.6%, respectively. The total number of DCD in China has accumulated to 1564 cases, and 4243 organs were transplanted. To alleviate the further difficulties of donation, establishment of professional organ procurement organizations in transplant hospitals, legislation of brain death, and promulgation of legal guidelines on DCD will be the main targets of organ donation development in China.
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Obtenção de Tecidos e Órgãos/tendências , ChinaRESUMO
BACKGROUND/AIMS: Ischemia/reperfusion injury plays a crucial role in renal transplantation and represents a significant risk factor for acute kidney injury and delayed graft function. Mitochondria-targeted antioxidant peptide SS31 has been shown to attenuate ischemia/reperfusion injury by inhibiting oxidative stress. The present study was carried out to investigate whether the pretreatment of SS31 could reduce hypoxia/reoxygenation (H/R)-induced injury by inhibiting p66Shc. METHODS: The cultured rat renal proximal tubular cell line NRK52E cells were exposed to 24 h hypoxia (5% CO2, 1% O2, 94% N2) followed by 6 h reoxygenation (5% CO2, 21% O2, 74% N2). SS31 was added to the culture medium 4 h prior to the treatment. Then the cell viability, apoptosis, and oxidative stress levels were determined. In addition, western blot analysis was performed to determine the expression of p66Shc, p-p66Shc, cytochrome c, and caspase-3. RESULTS: H/R induced apoptotic cell death, accompanied with activation of total and p-p66Shc in NRK52E cells. Pretreatment with SS31 or overexpression of a dominantnegative Ser36 mutant p66Shc (p66Shc S36A) or p66Shc siRNA prevented cell death, whereas the protection effect of SS31 was completely blocked by overexpression of wild-type p66Shc. Furthermore, SS31 pretreatment reduced H/R-induced intracellular oxidative stress, cytochrome c translocation to the cytoplasm, and caspase-3 activation through inhibiting p66Shc. CONCLUSION: This study revealed that SS31 pretreatment serves a protective role against H/R-induced apoptosis of human renal tubular epithelial cells, and the mechanism is related to suppression of p66Shc.
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Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Hipóxia Celular , Mitocôndrias/efeitos dos fármacos , Oligopeptídeos/farmacologia , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Animais , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Túbulos Renais Proximais/citologia , Malondialdeído/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Adaptadoras da Sinalização Shc/antagonistas & inibidores , Proteínas Adaptadoras da Sinalização Shc/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de SrcRESUMO
Group A beta-hemolytic streptococcus (GABHS) infections are implicated in neuropsychiatric disorders associated with an increased expression of repetitive stereotyped movements. Anti-streptococcus IgG presumably cross-reacts with elements on basal ganglia cells, modifies their function, and triggers symptoms. IgM may play a unique role in precipitating behavioral disturbances since variations in cortico-striatal activity occur in temporal congruity with peak IgM titers during an orchestrated immune response. We discovered in Balb/c mice that single subcutaneous injections of mouse monoclonal IgM antibodies to streptococcus group A bacteria induce marked dose-dependent increases in repetitive stereotyped movements, including head bobbing, sniffing, and intense grooming. Effects were antibody- and antigen-specific: anti-streptococcus IgG stimulated ambulatory activity and vertical activity but not these stereotypies, while anti-KLH IgM reduced activity. We suggest that anti-streptococcus IgM and IgG play unique roles in provoking GABHS-related behavioral disturbances. Paralleling its stereotypy-inducing effects, anti-streptococcus IgM stimulated Fos-like immunoreactivity in regions linked to cortico-striatal projections involved in motor control, including subregions of the caudate, nucleus accumbens, and motor cortex. This is the first evidence that anti-streptococcus IgM antibodies induce in vivo functional changes in these structures. Moreover, there was a striking similarity in the distributions of anti-streptococcus IgM deposits and Fos-like immunoreactivity in these regions. Of further importance, Fcα/µ receptors, which bind IgM, were present- and co-localized with anti-streptococcus IgM in these structures. We suggest that anti-streptococcus IgM-induced alterations of cell activity reflect local actions of IgM that involve Fcα/µ receptors. These findings support the use of anti-streptococcus monoclonal antibody administration in Balb/c mice to model GABHS-related behavioral disturbances and identify underlying mechanisms.
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Anticorpos Antibacterianos/farmacologia , Anticorpos Monoclonais Murinos/farmacologia , Imunoglobulina M/farmacologia , Comportamento Estereotipado/efeitos dos fármacos , Transtorno de Movimento Estereotipado/imunologia , Streptococcus pyogenes/imunologia , Animais , Gânglios da Base/efeitos dos fármacos , Gânglios da Base/imunologia , Hemocianinas/imunologia , Imunoglobulina G/farmacologia , Imunoglobulina M/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Córtex Motor/efeitos dos fármacos , Córtex Motor/imunologia , Proteínas Proto-Oncogênicas c-fos/imunologia , Receptores Fc/imunologiaRESUMO
The aim of our study was to illustrate the role of circular RNA 0120175 (circ_0120175) and its associated mechanism in laryngeal squamous cell carcinoma (LSCC) development. The abundance of circ_0120175, microRNA-330-3p (miR-330-3p) and solute carrier family 7, membrane 11 (SLC7A11) messenger RNA and protein was measured by quantitative real time polymerase chain reaction and Western blot assay. Cell proliferation, apoptosis, migration and invasion were assessed by cell counting kit-8 assay, flow cytometry and transwell migration and invasion assays, respectively. The interaction between miR-330-3p and circ_0120175 or SLC7A11 was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to test the function of circ_0120175 in tumor growth in vivo. Circ_0120175 abundance was aberrantly increased in LSCC tissues and cell lines, and LSCC patients with high level of circ_0120175 were associated with advanced tumor staging, lymph node metastasis and short survival time. Circ_0120175 interference suppressed cell proliferation, migration and invasion and induced cell apoptosis of LSCC cells. Circ_0120175 could sponge and negatively regulate miR-330-3p expression in LSCC cells. The addition of anti-miR-330-3p partly reversed circ_0120175 knockdown-induced effects in LSCC cells. SLC7A11 bound to miR-330-3p. Circ_0120175 enhanced the abundance of SLC7A11 through sponging miR-330-3p in LSCC cells. Circ_0120175 silencing-mediated influences in LSCC cells were partly counteracted by the overexpression of SLC7A11. Circ_0120175 interference notably suppressed xenograft tumor growth in vivo. Circ_0120175 promoted proliferation, migration and invasion while impeded cell apoptosis of LSCC cells through miR-330-3p/SLC7A11 axis, which provided novel therapeutic targets for LSCC.
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Neoplasias de Cabeça e Pescoço , MicroRNAs , Sistema y+ de Transporte de Aminoácidos , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVES: To investigate the occurrence of unwanted pregnancies among renal transplant recipients and to identify major contributing factors. METHODS: A total of 647 women of childbearing age who had received a renal transplant at one of the five participating hospitals in China were enrolled in the study and administered a questionnaire that collected information on their reproductive health, pregnancies, and awareness and use of contraceptive methods. RESULTS: Of the 647 eligible patients, 98 (15%) reported 133 unwanted pregnancies post-transplantation. In this group (n = 98), despite an awareness of the available contraceptive measures, 56% had not applied any method of contraception, while 20% had relied on the rhythm method, and in only 12% of the cases male condoms had been used. The most common reason for not using contraception was a failure to realise that their reproductive function had been restored to normal soon after transplantation (19%). CONCLUSION In female renal transplant recipients, unprotected sex combined with incorrect judgment about their own reproductive potential post-transplantation were the major causes of unwanted pregnancies. The latter could be avoided through counselling about the risk pregnancy entails and the implementation of appropriate contraceptive measures.
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Conhecimentos, Atitudes e Prática em Saúde , Transplante de Rim , Gravidez não Desejada , Aborto Induzido , Adulto , China , Preservativos , Aconselhamento , Feminino , Humanos , Modelos Logísticos , Métodos Naturais de Planejamento Familiar , Educação de Pacientes como Assunto , Gravidez , Reprodução/fisiologia , Inquéritos e Questionários , Sexo sem Proteção/prevenção & controle , Adulto JovemRESUMO
Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) and may influence renal graft survival. In this study, we investigate the involvement of SIRT3 and DRP1 in mitochondrial autophagy and AKI in a mouse model of IRI. Autophagy was detected in the absence of SIRT3, and hypoxic reoxygenation (H/R) experiments using renal tubular epithelial cells NRK52E were performed in vitro to validate these results. We found that autophagosomes increased following IRI and that the expression of autophagy-related genes was up-regulated. The inhibition of autophagy with 3-methyladenine exacerbated IRI, whereas the DRP1 inhibitor Mdivi-1 reversed this inhibition. Mdivi-1 did not reverse the inhibition of autophagy in the absence of SIRT3. During IRI, Mdivi-1 reduced autophagy and DRP1 expression, whereas SIRT3 overexpression attenuated this condition. Rescue experiment showed that autophagy was increased when both SIRT3 or DRP1 were over- or under-expressed or just DRP1 was under-expressed but expression was reduced when just SIRT3 was under-expressed. However, the expression of DRP1-related molecules was reduced when SIRT3 was overexpressed and when DRP1 was under-expressed. Taken together, these findings indicate that SIRT3 protects against kidney damage from IRI by modulating the DRP1 pathway to induce mitochondrial autophagy.
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Autofagia , Dinaminas/metabolismo , Rim/irrigação sanguínea , Mitocôndrias/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Sirtuína 3/fisiologia , Animais , Biomarcadores/metabolismo , Linhagem Celular , Dinaminas/genética , Inativação Gênica , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão/patologia , Sirtuína 3/genéticaRESUMO
BACKGROUND: Patients with early-stage renal cell carcinoma (RCC) are considered to be eligible donors. Although preliminary experience in using kidneys of specific pathologic types, mainly those with small renal masses (SRMs), have been established, multiorgan utilization of the same donor with SRMs is limited. METHODS: One deceased donor whose left-side kidney was diagnosed with Fuhrman grade I RCC was included. The tumor mass in the kidney was removed through partial nephrectomy according to the gold standard. Then, 3 transplant surgeries were performed, in which 1 recipient accepted kidney transplant after tumor exeresis, 1 simultaneous heart-kidney (the contralateral one) transplant, and 1 liver transplant. Recipients were followed up according to our standard protocol for renal cancers. (All allografts were allocated in compliance with the Declaration of Helsinki and the Declaration of Istanbul.) RESULTS: After 32 months, no radiographic findings showed any morphologic changes of the lesion, and all patients were in good condition, with neither tumor recurrence nor allograft rejection or infection. No complaints such as pain, oliguria, dyspnea, nausea, or fatigue were recorded. CONCLUSIONS: To the best of knowledge, this initial work takes the lead in elaborating the organ utilization of multiorgan donors with SRMs. We hope the experience will provide support for cross discussion concerned with multiorgan transplant from tumor-affected donors in clinical practices, further expand the donor pool and address the donor shortage problem.
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Carcinoma de Células Renais , Neoplasias Renais , Transplante de Rim , Carcinoma de Células Renais/cirurgia , Sobrevivência de Enxerto , Humanos , Neoplasias Renais/cirurgia , Transplante de Rim/efeitos adversos , Recidiva Local de Neoplasia , Doadores de TecidosRESUMO
BACKGROUND: Although living kidney transplantation has numerous advantages over cadaveric transplantation, donor apprehension remains a problem. This study investigated psychosocial features and quality of life in Chinese living kidney donors after transplantation procedures. METHODS: Participants were 84 donors interviewed during follow-up after donation. Sociodemographic characteristics were evaluated by a 22-item questionnaire. Social support, quality of life, depression, and anxiety were objectively measured with the Social Support Rating Scale for Chinese, the Short-Form 36 Health Survey, the modified Beck Depression Inventory, and the Self-Rating Anxiety Scale questionnaire, respectively. RESULTS: All donors volunteered without pressure from families or recipients. Altruistic motives were the main impetus for donation, and donors had good social support. Living transplantation affected donors' quality of life, with a slight negative effect on some physical aspects. There were no major depressive or anxiety disorders following donation. CONCLUSIONS: Living kidney donation was a generally positive experience without evidence of major psychological disturbance. However, considering the limited size and duration of our study, we recommend careful follow-up of all donors. We also recommend provision of social support services and removal of financial disincentives for donors.
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Povo Asiático/psicologia , Transplante de Rim/psicologia , Doadores Vivos/psicologia , Qualidade de Vida , Ajustamento Social , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Rigorous donor evaluation is essential for living related donor kidney transplantation (LRDKT). However, guidelines for living kidney donor evaluation are absent in China. The aim of this study is to describe the initial experience in the living kidney donor evaluation process in a single transplant center in China. METHODS: The evaluation process of our center is sequentially divided into five steps: outpatient consultation and information, preliminary evaluation, comprehensive evaluation, final informed consent, and ethics committee oversight. RESULTS: Between June 2007 and March 2009, 124 potential living donors were evaluated in our center, of whom 82 (66.1%) became effective donors and the remaining 42 (33.9%) were excluded. The exclusion reasons were related to clinical problems in 27 cases, psychosocial problems in seven cases, and suspected organ trading in eight cases. CONCLUSION: Although strongly forbidden by Chinese laws, organ trading remains a threat to the healthy development of LRDKT in China. To prohibit organ trading, the kinship between the donor and recipient should be carefully identified. Guidelines for living donor evaluation appropriate to the actual situation in China should be set up for the sake of safety and to protect the rights and interests of both donors and recipients.