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1.
Transpl Immunol ; 85: 102077, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38950754

RESUMO

Systemic lupus erythematosus (SLE) is usually regarded as a relative contraindication for deceased kidney donation. The pathological variations because of the changes in the immune environment after kidney transplantation (KT) are unclear, and the recovery of renal function is poorly understood. We present a case of KT from a deceased donor with SLE who was followed-up for one year. Although SLE-related hemangioma developed during the perioperative period, it was cured after interventional treatment. A pre-planned biopsy was performed one year after KT, and it was found that most of the pathological changes and immunofluorescent markers of lupus had resolved. Renal function was stable, and urinary protein and occult blood levels reduced one year after KT.


Assuntos
Transplante de Rim , Lúpus Eritematoso Sistêmico , Doadores de Tecidos , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Feminino , Seguimentos , Hemangioma , Adulto , Rim/patologia , Pessoa de Meia-Idade
2.
Front Immunol ; 15: 1360955, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633259

RESUMO

With a shortage of organs for transplant, the use of marginal donors can be an effective measure to meet the shortfall. Myelodysplastic syndromes (MDS) are considered an absolute contraindication for organ donation because of the high invasive potential. Currently, organ transplantation from donors with a past history of MDS has not been reported. In this paper, we report the successful clinical experience of one liver transplantation and two kidney transplantations, with organs donated by a 39-year-old patient diagnosed with a past history of MDS following intracranial hemorrhage. Four and a half years after transplantation, the three recipients are all doing well. However, it is still not clear to what extent organs donated by patients with a past history of MDS can be safely transplanted. This report provides support for the careful use of marginal donors. With effective treatment and full peer assessment, livers and kidneys from donors with a past history of MDS may be safely transplanted.


Assuntos
Transplante de Fígado , Síndromes Mielodisplásicas , Humanos , Adulto , Doadores de Tecidos , Rim , Fígado
3.
Hum Cell ; 37(2): 420-434, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38133876

RESUMO

Hypothermic machine perfusion (HMP) has been demonstrated to be more effective in mitigating ischemia-reperfusion injury (IRI) of donation after circulatory death (DCD) organs than cold storage (CS), yet the underlying mechanism remains obscure. We aimed to propose a novel therapeutic approach to ameliorate IRI in DCD liver transplantation. Twelve clinical liver samples were randomly assigned to HMP or CS treatment and subsequent transcriptomics analysis was performed. By combining in vivo HMP models, we discovered that HMP attenuated inflammation, oxidative stress, and apoptosis in DCD liver through a SEPRINA3-mediated PI3Kδ/AKT signaling cascade. Moreover, in the hypoxia/reoxygenation (H/R) model of BRL-3A, overexpression of SERPINA3 mitigated H/R-induced apoptosis, while SERPINA3 knockdown exacerbated cell injury. Idelalisib (IDE) treatment also reversed the protective effect of SERPINA3 overexpression. Overall, our research provided new insights into therapeutic strategies and identified potential novel molecular targets for therapeutic intervention against DCD liver.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Serpinas , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fígado/metabolismo , Perfusão , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Serpinas/metabolismo
4.
Exp Clin Transplant ; 21(9): 749-755, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37885291

RESUMO

OBJECTIVES: Drain tube management after liver transplant is controversial. A new peritoneal drainage management protocol was developed to validate clinical characteristics, such as drain characteristics, postoperative complications, duration of postoperative hospital stay, changes in albumin levels, and 30-day readmission rates. MATERIALS AND METHODS: Data from 183 consecutive patients who underwent deceased donor liver transplant at our institution between January 2019 and June 2022 were retrospectively analyzed. A new drain management protocol was implemented on August 1, 2021, which included early removal of the drain tube when the serum albumin level was >3 g/dL and nonchylous fluid drainage was <200 mL/day. RESULTS: When we compared the traditional and new drain management protocol groups (n = 131 vs n = 52), the new management protocol group showed a decrease in the median duration of intraperitoneal drainage. In addition, the median length of postoperative hospital stay decreased from 33 to 27 days and serum albumin levels returned to normal faster at postoperative 3 weeks. No significant differences were found in postoperative hemorrhage, hematoma, hydrops abdominis, infections, biliary complications, orin the rate ofreinterventions and 30-day rehospitalizations. CONCLUSIONS: The new management protocol was associated with fewer postoperative hospital days and faster recovery than traditional management. Our findings may aid in the development of new drain policy recommendations based on preexisting risk factors.


Assuntos
Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Doadores Vivos , Drenagem/efeitos adversos , Drenagem/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Tempo de Internação , Albumina Sérica , Hospitais
6.
Curr Med Sci ; 43(2): 417-420, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37037972

RESUMO

Donor-derived infection (DDI) associated with Scedosporium spp is extremely rare, and results in a very poor prognosis. The present study reports a probable DDI due to Scedosporium boydii (S. boydii) from a donor with neuropsychiatric systemic lupus erythematosus. Two recipients developed Scedosporiosis after kidney transplantation from the same donor. Recipient 1 died of central nervous system infection due to S. boydii based on the clinical presentations, and the positive metagenomic next-generation sequencing (mNGS) and culture results for the cerebrospinal fluid. The other recipient with urinary tract obstruction due to S. boydii, which was identified through the positive culture and mNGS results of the removed stents, was successfully treated by stent replacement and voriconazole administration. Undiagnosed disseminated donor infection and the transmission of S. boydii should be given attention, particularly when the donor and recipients have primary immunodeficiency disease. The screening of donors and recipients for S. boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients, due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.


Assuntos
Infecções Fúngicas Invasivas , Transplante de Rim , Lúpus Eritematoso Sistêmico , Humanos , Transplante de Rim/efeitos adversos , Voriconazol/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico
7.
Transpl Immunol ; 76: 101725, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36181973

RESUMO

BACKGROUND: Passenger lymphocyte syndrome (PLS) is a rare post solid organ transplantation complication, usually occurring after ABO- or Rh-mismatched transplantation. In general, PLS can lead to severe hemolytic anemia, but it is usually a self-limited disease. Most PLS cases start with a decreased hemoglobin (Hb) level and require donor type RBC transfusion as the only treatment. CASE REPORT: In our case, the allograft was given by an O-type Rh-D(+) donor and received by an A-type Rh-D(+) recipient. The PLS was developed on the post-operative day (POD) 10 with an increased indirect bilirubin (IDBIL) level as the first clinical symptom, while the Hb level did not significantly decrease. The PLS was diagnosed on POD 17 by a direct antiglobulin test (DAT) and a blood group test. The patient quickly became stable on POD 18 after a total of eight units of O-type RBC transfusion. Kidney function was uneventful in the entire PLS period. CONCLUSION: In ABO-mismatched kidney transplantation, an increased level of IDBIL should be considered as the first symptom of PLS even without an Hb decrease. The kidney function may be not affected by the PLS symptoms.


Assuntos
Transplante de Rim , Humanos , Incompatibilidade de Grupos Sanguíneos , Sistema ABO de Grupos Sanguíneos , Transplante Homólogo , Linfócitos , Síndrome
8.
Front Genet ; 13: 1065693, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479252

RESUMO

Background: The inadequate early detection strategies makes hepatocellular carcinoma (HCC) patients with poor prognisis. Therefore, more effective detection methods are urgently needed for early detection and early intervention of HCC. Methods: 17 cases of suspected HCC patients and 11 cases of HBV-related decompensated cirrhosis (HBV-DeCi) patients were enrolled. For each patient, 5 ml blood sample was separated into circulating tumor cells (CTCs) and plasma, CTCs were stained with Diff staining for counting. Plasma was used for extracting cell free DNA (cfDNA) and then analyzed by qMSP assay. Ct values were recorded for GNB4 and Riplet as target genes and ß-actin as an endogenous reference gene. Finally, clinical efficacy of CTC count combined with GNB4/Riplet methylation detection for early diagnosis of HCC was analyzed. Results: The CTC of HCC patients has pleomorphic characteristics, but it is difficult to distinguish from other blood cells with non-obviously pleomorphic of CTC. Although a small number of CTCs can also be detected in HBV-DeCi patients (control group), the number is significantly lower than that in HCC patients, the sensitivity and specificity of CTC for HCC detection were 70.6% and 90.9% (AUC = 0.81). The Ct values of GNB4 and Riplet methylation were significantly different between HCC patients and control group patients. When CTC combined with two genes, the AUC value was significantly increased to 0.98, the sensitivity was 88.2%, and the specificity was 100%. Conclusion: Our study has developed a novel test that CTC count combined with GNB4/Riplet methylation detection and showed its high performance for early diagnosis of HCC.

9.
Altern Ther Health Med ; 28(7): 52-57, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35839107

RESUMO

Background: The aim of this study was to determine the efficacy of interferon (IFN)-based therapy for coronavirus disease 2019 (COVID-19) based on relevant qualified studies. We searched for pertinent studies using keywords via PubMed, Cochrane and Embase databases. Studies from other pertinent sources and that were published before September 2021 were also reviewed. Methods: For each study, we assessed and synthesized the outcomes by relative risk (RR) or weighted mean difference (WMD) combined with a 95% confidence interval (CI). A total of 8 studies involving 2442 patients with COVID-19 were evaluated in this meta-analysis. Results: The IFN group had a significant decrease in ICU admissions (RR: 0.705; 95% CI, 0.515-0.964) and death (RR: 0.416; 95% CI, 0.217-0.797), and increased duration of ICU stay (WMD: 0.996; 95% CI, 0.834-1.158) compared with the control group in the randomized clinical trial (RCT) subgroup analysis. In non-RCT subgroup analysis, the IFN group showed a significant increase in discharge rate (RR: 1.052; 95% CI, 1.004-1.101) compared with the control group. Conclusion: IFN therapy appears to have better efficacy than non-IFN therapy as sedatives in patients with COVID-19 in terms of decreasing ICU admissions and death and increasing discharge. However, more high-quality RCTs are needed to confirm these findings.


Assuntos
Tratamento Farmacológico da COVID-19 , Humanos , Hipnóticos e Sedativos , Imunoterapia , Interferons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Hepatobiliary Pancreat Dis Int ; 21(2): 106-112, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34583911

RESUMO

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Humanos , Imunossupressores/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Sirolimo/efeitos adversos , Resultado do Tratamento
11.
Artif Organs ; 46(2): 219-228, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34252214

RESUMO

Ischemia-reperfusion injury (IRI) is the major cause of delayed graft function (DGF) during the posttransplantation period. Estradiol (E2) prevents IRI-induced kidney dysfunction and tissue injury. However, many side effects limit E2's in vivo application. Recent evidence uncovers E2's expanded use in the field of transplantation. We aimed to study if and how E2 exerts protective activity during the period of kidney organ preservation. The autologous kidney transplant model in rats was first established. Rats were divided into 5 groups: normal group (N), sham group (sham), static cold storage (SCS) 4 hours group (control), SCS 4 hours + ethanol (1 µL/mL) group (solvent), and SCS 4 hours + ethanol (1 µL/mL) + E2 (1000 ng/mL) group (E2). ERα expression under hypothermia was measured by western blotting. Moreover, biochemical analyses of plasma levels of creatinine, BUN, estradiol, and testosterone were examined. Among all groups, kidney tissues were collected and processed for further western blot analysis about ERα, eNOS, Bcl-2, and Bax expression, histological analyses such as H&E staining to evaluate pathological severity. In addition, a TUNEL assay is performed to evaluate apoptosis. E2 copreservation upregulated ERα expression under hypothermia. Moreover, E2 copreservation reduced levels of creatinine and BUN in plasma but without affecting estradiol and testosterone. Further, E2 copreservation increased expression of eNOS and antiapoptotic Bcl-2 and decreases expression of proapoptotic Bax. E2 copreservation significantly inhibited IRI-induced apoptosis and evidently improved pathological severity in the kidney of rats. E2 copreservation exerts protective activity against IRI-induced pro-inflammatory and proapoptotic effects in kidneys during organ preservation time and improves transplanted kidney function.


Assuntos
Estradiol/farmacologia , Transplante de Rim , Preservação de Órgãos , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Estradiol/sangue , Etanol , Rim/patologia , Masculino , Ratos Sprague-Dawley , Testosterona/sangue
12.
Transplant Proc ; 53(10): 2963-2970, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34736781

RESUMO

BACKGROUND: The aims of this study were to investigate the pathologic manifestation of pretransplant biopsy and to provide an accurate assessment method for liver graft of China Donation after Citizen's Death (CDCD). METHODS: A retrospective analysis was performed based on clinical and biopsy data of 96 CDCD liver transplantations completed between January 2012 and December 2017. The pretransplant pathologic sections were semiquantitatively scored according to Banff Schema recommendations on liver allograft pathology. Graft overall survival (OS) and early allograft dysfunction (EAD) rates were observed. RESULTS: The histologic analysis of the 96 CDCD liver graft biopsy specimens was summarized, including portal area neutrophilic infiltrate, macrovesicular steatosis, microvesicular steatosis, and hepatocellular swelling. Among these pathologic characteristics, only portal area neutrophilic infiltrate ≥20% was an independent risk factor for graft survival, although it has limited effect on the recipient's short-term prognosis. CONCLUSIONS: We found that portal area neutrophilic infiltrate ≥20% was an independent risk factors for long-term graft survival. According to this criterion, we can identify liver transplant recipients at risk for poor prognosis and make timely interventions.


Assuntos
Transplante de Fígado , Sobrevivência de Enxerto , Humanos , Fígado , Doadores Vivos , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos
14.
Cell Death Dis ; 12(2): 211, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627626

RESUMO

Ischemia-reperfusion injury (IRI) is an inevitable and serious clinical problem in donations after heart death (DCD) liver transplantation. Excessive sterile inflammation plays a fateful role in liver IRI. Hypothermic oxygenated perfusion (HOPE), as an emerging organ preservation technology, has a better preservation effect than cold storage (CS) for reducing liver IRI, in which regulating inflammation is one of the main mechanisms. HECTD3, a new E3 ubiquitin ligase, and TRAF3 have an essential role in inflammation. However, little is known about HECTD3 and TRAF3 in HOPE-regulated liver IRI. Here, we aimed to investigate the effects of HOPE on liver IRI in a DCD rat model and explore the roles of HECTD3 and TRAF3 in its pathogenesis. We found that HOPE significantly improved liver damage, including hepatocyte and liver sinusoidal endothelial cell injury, and reduced DCD liver inflammation. Mechanistically, both the DOC and HECT domains of HECTD3 directly interacted with TRAF3, and the catalytic Cys (C832) in the HECT domain promoted the K63-linked polyubiquitination of TRAF3 at Lys138. Further, the ubiquitinated TRAF3 at Lys138 increased oxidative stress and activated the NF-κB inflammation pathway to induce liver IRI in BRL-3A cells under hypoxia/reoxygenation conditions. Finally, we confirmed that the expression of HECTD3 and TRAF3 was obviously increased in human DCD liver transplantation specimens. Overall, these findings demonstrated that HOPE can protect against DCD liver transplantation-induced-liver IRI by reducing inflammation via HECTD3-mediated TRAF3 K63-linked polyubiquitination. Therefore, HOPE regulating the HECTD3/TRAF3 pathway is a novel target for improving IRI in DCD liver transplantation.


Assuntos
Hipotermia Induzida , Circulação Hepática , Fígado/irrigação sanguínea , Fígado/cirurgia , Preservação de Órgãos , Perfusão , Traumatismo por Reperfusão/prevenção & controle , Fator 3 Associado a Receptor de TNF/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Hipóxia Celular , Linhagem Celular , Modelos Animais de Doenças , Hepatectomia , Humanos , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Transplante de Fígado , Masculino , Estresse Oxidativo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator 3 Associado a Receptor de TNF/genética , Coleta de Tecidos e Órgãos , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
15.
Exp Ther Med ; 21(3): 256, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33603863

RESUMO

Establishing a steatotic liver transplantation animal model can be a challenging process, which requires complex microsurgical technologies. The present study established a novel rat model of stable steatotic liver transplantation for marginal liver graft research, which notably minimized the number of animals used for the experiment. Briefly, male Sprague-Dawley rats (n=90) were fed with a high-fat diet (HFD; 60%, kJ) or standard chow diet (SCD) for 8 weeks. The liver enzymes and lipid levels were assessed every week, and the degree of steatosis was determined via hematoxylin and eosin and Oil Red O staining. The results demonstrated that there were no significant differences in alanine aminotransaminase and aspartate aminotransferase levels between the SCD and HFD groups (P>0.05), whereas the level of plasma triglyceride (TG) increased by 1.76-fold in the HFD group at week 2, and progressively decreased to baseline levels by week 8. Significantly higher levels of TG were observed in the HFD group compared with the SCD group at week 2 (P<0.05). In addition, the levels of plasma glucose (P<0.05), portal insulin (P<0.05) and content of liver lipid (P<0.01) increased in the HFD group compared with the SCD group. After 6 weeks, the liver steatosis was successfully formed and stable. Consequently, a rat liver developed hepatic macrovesicular steatosis >60%, which was subsequently used for transplantation after double-lobectomy. Post-transplantation survival rates in the HFD and SCD groups were as follows: Week 1, 80 vs. 100% and 1 month, 20 vs. 100%. A total of 20 rats were not sacrificed by performing double-lobectomy for biopsy. Taken together, the results of the present study suggest that rat liver double-lobectomy may be safely applied in steatotic liver transplantation without the need to sacrifice a large number of animals.

16.
J Immunol Res ; 2021: 9289719, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34988230

RESUMO

Hepatocellular carcinoma (HCC) is the most prevalent type of hepatic carcinoma. Long noncoding RNAs (lncRNAs) are considered crucial regulators of gene expression; however, their functions in HCC are not well understood. Thus, the present study is aimed at elucidating the functions of the lncRNA HOXA-AS3 in HCC. The functions of the HOXA-AS3/miR-455-5p/programmed death-ligand 1 (PD-L1) axis were investigated in vitro via qRT-PCR and dual-luciferase reporter assays. The effect of HOXA-AS3 expression on tumor growth and metastasis was assessed using a mouse xenograft model. High HOXA-AS3 expression was observed in the HCC cell lines. Furthermore, overexpression of HOXA-AS3 in HCC cells enhanced proliferation, migration, and invasion, regulated the cell cycle, and retarded apoptosis. We also identified an miR-455-5p binding site in HOXA-AS3. By sponging miR-455-5p, HOXA-AS3 increased the expression of PD-L1. Additionally, both the inhibition of PD-L1 and overexpression of miR-455-5p reversed the effects on cell proliferation and invasion triggered by the overexpression of HOXA-AS3. In conclusion, HOXA-AS3 modulated the functions of HCC cells through the miR-455-5p/PD-L1 axis. Therefore, HOXA-AS3 may be a novel therapeutic target for HCC.


Assuntos
Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Apoptose/genética , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Interferência de RNA
17.
Front Immunol ; 12: 767618, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35111153

RESUMO

Renal transplantation is currently the most effective treatment for end-stage renal disease. However, chronic antibody-mediated rejection (cABMR) remains a serious obstacle for the long-term survival of patients with renal transplantation and a problem to be solved. At present, the role and mechanism underlying immune factors such as T- and B- cell subsets in cABMR after renal transplantation remain unclear. In this study, single-cell RNA sequencing (scRNA-seq) of peripheral blood monocytes (PBMCs) from cABMR and control subjects was performed to define the transcriptomic landscape at single-cell resolution. A comprehensive scRNA-seq analysis was performed. The results indicated that most cell types in the cABMR patients exhibited an intense interferon response and release of proinflammatory cytokines. In addition, we found that the expression of MT-ND6, CXCL8, NFKBIA, NFKBIZ, and other genes were up-regulated in T- and B-cells and these genes were associated with pro-inflammatory response and immune regulation. Western blot and qRT-PCR experiments also confirmed the up-regulated expression of these genes in cABMR. GO and KEGG enrichment analyses indicated that the overexpressed genes in T- and B-cells were mainly enriched in inflammatory pathways, including the TNF, IL-17, and Toll-like receptor signaling pathways. Additionally, MAPK and NF-κB signaling pathways were also involved in the occurrence and development of cABMR. This is consistent with the experimental results of Western blot. Trajectory analysis assembled the T-cell subsets into three differentiation paths with distinctive phenotypic and functional prog rams. CD8 effector T cells and γδ T cells showed three different differentiation trajectories, while CD8_MAI T cells and naive T cells primarily had two differentiation trajectories. Cell-cell interaction analysis revealed strong T/B cells and neutrophils activation in cABMR. Thus, the study offers new insight into pathogenesis and may have implications for the identification of novel therapeutic targets for cABMR.


Assuntos
Anticorpos/imunologia , Rejeição de Enxerto/imunologia , Transcriptoma/imunologia , Animais , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Citocinas/imunologia , Perfilação da Expressão Gênica/métodos , Humanos , Inflamação/imunologia , Transplante de Rim/métodos , Macaca mulatta , Camundongos , Monócitos/imunologia , Transdução de Sinais/imunologia , Análise de Célula Única/métodos , Regulação para Cima/imunologia
18.
Transpl Infect Dis ; 23(1): e13425, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32702153

RESUMO

There is no consensus on immunosuppression management for kidney transplant recipients (KTRs) with SARS-CoV-2 pneumonia. Therefore, we conducted a search in English database from October 2019 to July 2020 and extracted data from cases with treatment details worldwide, and total of 41 recipients with a median age of 50 years were enrolled in this study. Most of them were males (75.8%). The most common presenting symptoms were fever (80.5%), cough (63.4%), and fatigue (41.5%). Patients were classified into three catalogs according to severity of pneumonia: 17 (41.5%) were mild, 15 (36.6%) severe, and 9 (21.9%) critical disease. Laboratory tests revealed that serum creatinine of critical patients was significantly higher than that of mild or severe patients. 68.3% received oxygen support; all patients received antiviral therapy, and 15 (36.6%) recipients were additionally treated with intravenous immunoglobulin and interferon-α. 19.5% of patients maintained immunosuppressive therapy; 36.6% suspended antimetabolite; and 43.9% only treated with corticosteroid. Six (14.6%) patients died (severe: 2, critical: 4); high creatinine with low lymphocyte count was the biggest challenge of immunosuppression management. In all, it is necessary to pay close attention to renal function and lymphocyte count in KTRs infected with COVID-19 and choose appropriate medication programs according to the specific situations.


Assuntos
COVID-19/complicações , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Transplante de Rim , SARS-CoV-2 , Transplantados , Adolescente , Adulto , Idoso , COVID-19/imunologia , Saúde Global , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Mol Med Rep ; 22(3): 2373-2385, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32705206

RESUMO

Hepatic ischemia/reperfusion injury (HIRI) is a complex pathophysiological process that often leads to poor clinical prognosis. Clinically, the effective means to alleviate HIRI are limited. The aim of the present study was to investigate whether Alda­1, an activator of mitochondrial aldehyde dehydrogenase 2 (ALDH2), had a protective effect on HIRI and to investigate the mechanisms underlying this protective effect. Sprague­Dawley rats were treated with Alda­1 or Daidzin, an ALDH2 inhibitor, 30 min before partial (70%) warm liver ischemia to induce HIRI. The 48 rats were randomly divided into four groups: Sham, ischemia injury (IR), IR­Alda­1, and IR­Daidzin. After 6 and 24 h of reperfusion, serum and liver tissue samples were collected and stored for further experiments. Alanine aminotransferase, aspartate aminotransferase and hematoxylin & eosin staining was used to evaluate the liver damage. Western blotting and reverse transcription­quantitative PCR were used to detect the expression of related proteins and mRNA. TUNEL staining was used to observe the apoptosis of liver cells. Transmission electron microscopy was used to detect the mitochondrial injuries. Alda­1 pretreatment ameliorated the HIRI­induced damage to the liver function and reduced histological lesions. Alda­1 also increased ALDH2 activity after HIRI. Moreover, the pretreatment with Alda­1 reduced the accumulation of toxic aldehyde 4­hydroxy­2­nonenal, decreased the production of reactive oxygen species and malondialdehyde, reversed the damage to the liver mitochondria, attenuated hepatocyte apoptosis and inhibited the HIRI­induced inflammatory response, including high­mobility group box 1/toll­like receptor 4 signaling. Alda­1 also induced autophagy by upregulating autophagy­related 7 and Rab7 increasing the microtubule associated protein 1 light chain 3 αII/I ratio and inhibiting p62 expression. ALDH2­induced autophagy was dependent on the activation of the AKT/mammalian target of rapamycin (mTOR) and AMP­activated protein kinase (AMPK) signaling pathways. In conclusion, the findings of the present study suggested that Alda­1 may protect the liver against HIRI­induced damage, including hepatic enzyme injury, acetaldehyde accumulation, oxidative stress, hepatocyte apoptosis and inflammation. Alda­1 may confer this protection by inducing autophagy through the AKT/mTOR and AMPK signaling pathways. Therefore, ALDH2 could represent a potential pharmacological target in the clinical treatment of HIRI.


Assuntos
Benzamidas/administração & dosagem , Benzodioxóis/administração & dosagem , Hepatopatias/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Aldeídos/metabolismo , Animais , Autofagia , Benzamidas/farmacologia , Benzodioxóis/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatopatias/etiologia , Hepatopatias/metabolismo , Testes de Função Hepática , Masculino , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo
20.
Am J Transplant ; 20(7): 1916-1921, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32282986

RESUMO

Over 1 000 000 cases of coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID-19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus-related hepatocellular carcinoma and was confirmed to have COVID-19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low-dose methylprednisolone-based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living-related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID-19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID-19. These effectively treated cases can provide a basis for immunosuppressant management of COVID-19-positive SOT recipients.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Imunossupressores/uso terapêutico , Transplante de Órgãos , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Transplantados , Adulto , Betacoronavirus , COVID-19 , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Hepatite B/complicações , Hepatite B/cirurgia , Vírus da Hepatite B , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Pandemias , Prognóstico , SARS-CoV-2 , Resultado do Tratamento
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