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1.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 191-195, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678605

RESUMO

This study aimed to explore the influence of circFOXM1/miR-218-5p molecular axis in the proliferation, apoptosis and migration of glioma cells. The levels of circFOXM1 and miR-218-5p in glioma and adjacent tissues were tested by qRT-PCR. Cultured human glioma U251 cells were randomly split into groups: si-NC, si-circFOXM1, miR-NC, miR-218-5p, si-circFOXM1+anti-miR-NC, si-circFOXM1+anti-miR-218-5p. MTT method, plate clone formation, flow cytometry and Transwell experiments were utilized for detecting the proliferation, clone formation, apoptosis and migration of glioma cells. Dual-luciferase reporter experiment authenticated the targeted relation of circFOXM1 and miR-218-5p. Western blot tested the levels of E-cadherin and N-cadherin. CircFOXM1 was upregulated while miR-218-5p was low expressed in glioma tissues versus normal tissues. After circFOXM1 silence or miR-218-5p overexpression, miR-218-5p level was increased, and cell apoptosis rate and E-cadherin expression were enhancive, whereas cell proliferation, cell clone formation and migration abilities, and N-cadherin level were reduced. CircFOXM1 could affect miR-218-5 level by negative regulation. Furthermore, miR-218-5p silence could reverse the stimulative influence of si-circFOXM1 on apoptosis rate, and E-cadherin level, and the repressive effect on cell viability, cell number of colony formation and migration, and N-cadherin expression. Inhibition of circFOXM1 expression could block the proliferation, clone formation, and migration and induce apoptosis of glioma cells by upregulating miR-218-5p.


Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Proteína Forkhead Box M1 , Regulação Neoplásica da Expressão Gênica , Glioma , MicroRNAs , RNA Circular , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Apoptose/genética , Movimento Celular/genética , Glioma/patologia , Glioma/genética , Glioma/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , RNA Circular/genética , RNA Circular/metabolismo , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Caderinas/metabolismo , Caderinas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo
2.
Int Immunopharmacol ; 131: 111874, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38493695

RESUMO

BACKGROUND: Hepatic ischaemia-reperfusion injury (HIRI) is a major clinical concern during the perioperative period and is closely associated with early allograft dysfunction (EAD), acute rejection (AR) and long-term graft survival. Neutrophil extracellular traps (NETs) are extracellular structures formed by the release of decondensed chromatin and granular proteins following neutrophil stimulation. There is growing evidence that NETs are involved in the progression of various liver transplantation complications, including ischaemia-reperfusion injury (IRI). This study aimed to comprehensively analyse the expression patterns of NET-related genes (NRGs) in HIRI, identify HIRI subtypes with distinct characteristics, and develop a reliable EAD prediction model. METHODS: Microarray, bulk RNA-seq, and single-cell sequencing datasets were obtained from the GEO database. Initially, differentially expressed NRGs (DE-NRGs) were identified using differential gene expression analyses. We then utilised a non-negative matrix factorisation (NMF) algorithm to classify HIRI samples. Subsequently, we employed machine learning algorithms to screen the hub NRGs related to EAD and developed an EAD prediction model based on these hub NRGs. Concurrently, we assessed the expression patterns of hub NRGs at the single-cell level using the HIRI. Additionally, we validated C5AR1 expression and its effect on HIRI and NETs formation in a rat orthotopic liver transplantation (OLT) model. RESULTS: In this study, we identified 11 DE-NRGs in the HIRI context. Based on these 11 DE-NRGs, HIRI samples were classified into two distinct clusters. Cluster1 exhibited a low expression of DE-NRGs, minimal neutrophil infiltration, mild inflammation, and a low incidence of EAD. Conversely, Cluster2 displayed the opposite phenotype, with an activated inflammatory subtype and a higher incidence of EAD. Furthermore, an EAD prediction model was developed using the four hub NRGs associated with EAD. Based on risk scores, HIRI samples were classified into high- and low-risk groups. The OLT model confirmed substantial upregulation of C5AR1 expression in the liver tissue, accompanied by increased formation of NETs. Treatment with a C5AR1 antagonist improved liver function, reduced tissue inflammation, and decreased NETs formation. CONCLUSIONS: This study distinguished two apparent HIRI subtypes, established a predictive model for EAD, and validated the effect of C5AR1 on HIRI. These findings provide novel perspectives for the development of advanced clinical strategies to enhance the outcomes of liver transplant recipients.


Assuntos
Armadilhas Extracelulares , Traumatismo por Reperfusão , Ratos , Animais , Armadilhas Extracelulares/metabolismo , Fígado/metabolismo , Traumatismo por Reperfusão/metabolismo , Aloenxertos , Inflamação/metabolismo , Análise de Sequência de RNA
4.
Front Mol Biosci ; 10: 1269478, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074089

RESUMO

Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI. Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting. Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells. Conclusion: NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI.

5.
Front Cell Dev Biol ; 11: 1208566, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547477

RESUMO

Background: The role of the cellular level in kidney transplant rejection is unclear, and single-cell RNA sequencing (scRNA-seq) can reveal the single-cell landscape behind rejection of human kidney allografts at the single-cell level. Methods: High-quality transcriptomes were generated from scRNA-seq data from five human kidney transplantation biopsy cores. Cluster analysis was performed on the scRNA-seq data by known cell marker genes in order to identify different cell types. In addition, pathways, pseudotime developmental trajectories and transcriptional regulatory networks involved in different cell subpopulations were explored. Next, we systematically analyzed the scoring of gene sets regarding single-cell expression profiles based on biological processes associated with oxidative stress. Results: We obtained 81,139 single cells by scRNA-seq from kidney transplant tissue biopsies of three antibody-mediated rejection (ABMR) patients and two acute kidney injury (AKI) patients with non-rejection causes and identified 11 cell types, including immune cells, renal cells and several stromal cells. Immune cells such as macrophages showed inflammatory activation and antigen presentation and complement signaling, especially in rejection where some subpopulations of cells specifically expressed in rejection showed specific pro-inflammatory responses. In addition, patients with rejection are characterized by an increased number of fibroblasts, and further analysis of subpopulations of fibroblasts revealed their involvement in inflammatory and fibrosis-related pathways leading to increased renal rejection and fibrosis. Notably, the gene set score for response to oxidative stress was higher in patients with rejection. Conclusion: Insight into histological differences in kidney transplant patients with or without rejection was gained by assessing differences in cellular levels at single-cell resolution. In conclusion, we applied scRNA-seq to rejection after renal transplantation to deconstruct its heterogeneity and identify new targets for personalized therapeutic approaches.

6.
Ann Transplant ; 28: e939343, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37043447

RESUMO

BACKGROUND The aim of this study was to explore the evaluation and use of donor organs from donors with brain death caused by acute severe organophosphorus pesticides and provide a basis for the use of such donor organs. MATERIAL AND METHODS Seven cases of brain dead donors caused by acute organophosphorus pesticide poisoning from January 2014 to December 2018 in the hospital were collected, and a retrospective analysis was made of the donors' age, race, physiological and pathological changes, donor organ function changes and the organ use, liver or kidney function recovery, and complications of the recipients. The 18 recipients were followed up until June 31, 2022. RESULTS We found that 71.42% of organ donors were male, and 71.42% of organ donors were under 50 years old. The main cause of death was respiratory failure caused by organophosphorus pesticide poisoning. The liver and kidney functions of 7 donors were damaged, and 3 livers could not be used due to severe functional damage, but the liver or kidney function of 18 recipients gradually recovered after transplantation. Delayed recovery of graft function occurred after transplantation accounted for 21.43%, and the grafts had good short-term to medium-term performance. CONCLUSIONS Although the function of organs from donor with brain death due to acute severe organophosphorus pesticide poisoning is seriously damaged, most of the organs can still be used for transplantation. Individualized functional maintenance according to the situation of donors is conducive to improving the quality of organs.


Assuntos
Transplante de Fígado , Praguicidas , Venenos , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Compostos Organofosforados , Praguicidas/toxicidade , Estudos Retrospectivos , Morte Encefálica , Doadores de Tecidos , Sobrevivência de Enxerto
7.
HLA ; 101(6): 696-697, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36635212

RESUMO

HLA-DRB1*04:357 differs from HLA-DRB1*04:17:02 by two nucleotides in exon 2.


Assuntos
População do Leste Asiático , Transplantados , Humanos , Sequência de Bases , Alelos , Cadeias HLA-DRB1/genética , Análise de Sequência de DNA
8.
Front Genet ; 13: 972043, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105093

RESUMO

Background: A high mortality rate makes hepatocellular carcinoma (HCC) one of the most common types of cancer globally. 5-methylcytosine (m5C) is an epigenetic modification that contributes to the prognosis of several cancers, but its relevance to HCC remains unknown. We sought to determine if the m5C-related regulators had any diagnostic or prognostic value in HCC. Methods: M5C regulatory genes were screened and compared between HCC and normal tissue from The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. Least absolute shrinkage and selection operator method (LASSO) and univariate Cox regression analysis of differentially expressed genes were then performed to identify diagnostic markers. A LASSO prognostic model was constructed using M5C regulatory genes with prognostic values screened by TCGA expression data. HCC patients were stratified based on risk score, then clinical characteristics analysis and immune correlation analysis were performed for each subgroup, and the molecular functions of different subgroups were analyzed using both Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). The prognostic model was evaluated using univariate and multivariate Cox analyses as well as a nomogram. Molecular typing was performed according to m5C regulatory genes and immune checkpoint genes expression respectively, and clinical characterization and immune correlation analysis were performed for each subgroup. Results: M5C regulatory genes are expressed differently in HCC patients with different clinical and pathological characteristics, and mutations in these genes are frequent. Based on five m5C regulators (NOP2, NSUN2, TET1, YBX1, and DNMT3B), we constructed a prognostic model with high predictive ability. The risk score was found to be an independent prognostic indicator. Additionally, risk scores can also be applied in subgroups with different clinical characteristics as prognostic indicators. Conclusion: The study combined data from TCGA and GEO for the first time to reveal the genetic and prognostic significance of m5C-related regulators in HCC, which provides new directions for identifying predictive biomarkers and developing molecularly targeted therapies for HCC.

9.
Transplant Proc ; 54(7): 1724-1729, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35973865

RESUMO

Within the last decade, deceased organ donation and transplantation in China have made great progress, but there is still much room for improvement. Inefficient communication with the family of potential organ and tissue donors is one of the major reasons for donor loss. In this study, the current progress of the deceased organ donation program in China was summarized, with a particular focus on the analysis of problems and solutions for achieving best practices in communication with the family of potential organ and tissue donors. This paper is in compliance with the Helsinki Congress and the Declaration of Istanbul.


Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Doadores de Tecidos , Povo Asiático , Comunicação
10.
Medicine (Baltimore) ; 101(27): e29628, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35801800

RESUMO

BACKGROUND: While protein kinase, DNA-activated, catalytic subunit (PRKDC) plays an important role in double-strand break repair to retain genomic stability, there is still no pan-cancer analysis based on large clinical information on the relationship between PRKDC and different tumors. For the first time, this research used numerous databases to perform a pan-cancer review for PRKDC to explore the possible mechanism of PRKDC in the etiology and outcomes in various tumors. METHODS: PRKDC's expression profile and prognostic significance in pan-cancer were investigated based on various databases and online platforms, including TIMER2, GEPIA2, cBioPortal, CPTAC, and SangerBox. We applied the TIMER to identified the interlink of PRKDC and the immune infiltration in assorted tumors, and the SangerBox online platform was adopted to find out the relevance between PRKDC and immune checkpoint genes, tumor mutation burden, and microsatellite instability in tumors. GeneMANIA tool was employed to create a protein-protein interaction analysis, gene set enrichment analysis was conducted to performed gene enrichment analysis. RESULTS: Overall, tumor tissue presented a higher degree of PRKDC expression than adjacent normal tissue. Meanwhile, patients with high PRKDC expression have a worse prognosis. PRKDC mutations were present in almost all The Cancer Genome Atlas tumors and might lead to a better survival prognosis. The PRKDC expression level was shown a positive correlation with tumor-infiltrating immune cells. PRKDC high expression cohorts were enriched in "cell cycle" "oocyte meiosis" and "RNA-degradation" signaling pathways. CONCLUSIONS: This study revealed the potential value of PRKDC in tumor immunology and as a therapeutic target and prognostic biomarker in pan-cancer.


Assuntos
Proteína Quinase Ativada por DNA , Neoplasias , Biomarcadores Tumorais/genética , Proteína Quinase Ativada por DNA/genética , Humanos , Instabilidade de Microssatélites , Neoplasias/diagnóstico , Neoplasias/genética , Prognóstico
11.
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
12.
Sci Prog ; 104(2): 368504211009665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861661

RESUMO

Organ donation provides a life-saving opportunity for patients with organ failure. China, like most countries, is faced with organ shortages. Understanding public opinion regarding organ donation in China is critical to ensure an increased donation rate. Our study explored public concerns and attitudes toward organ donation, factors involved, and how the public pays attention to organ donation. Sixteen million users' public information (i.e. gender, age, and geographic information) and posts from January 2017 to December 2017 were collected from Weibo, a social media platform. Of these, 1755 posts related to organ donation were included in the analysis. We categorized the posts and coded the users' attitudes toward organ donation and the associations between the demographics. The most popular posts mentioning organ donation were "publicly expressing the willingness to donate organs." Furthermore, 87.62% of posts exhibited a positive attitude toward organ donation, whereas only 7.44% exhibited a negative attitude. Most positive posts were "saluting the organ donors," and most negative posts involved "fear of the family's passive medical decision." There was no significant gender difference in the users' attitudes, but older people generally had a more negative attitude. Users with negative attitudes mainly distrust the medical system and are worried that the donated organs may be used in improper trading. Social media may be an important channel for promoting organ donation activities, and it is important to popularize scientific knowledge related to organ donation in order to eliminate the public's misunderstanding of organ donation and transplantation.


Assuntos
Transplante de Órgãos , Mídias Sociais , Obtenção de Tecidos e Órgãos , Idoso , Humanos , Opinião Pública , Doadores de Tecidos
13.
Ren Fail ; 43(1): 520-529, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33719820

RESUMO

BACKGROUND: Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. METHODS: This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. RESULTS: The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. CONCLUSIONS: Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.


Assuntos
Função Retardada do Enxerto/etiologia , Transplante de Rim/efeitos adversos , Doadores de Tecidos/estatística & dados numéricos , Adulto , Morte Encefálica , China , Isquemia Fria/efeitos adversos , Creatinina/análise , Função Retardada do Enxerto/terapia , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Transplantes/fisiopatologia
14.
Mol Med Rep ; 22(3): 2329-2341, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32705285

RESUMO

Transplantation is currently the best treatment for patients with end­stage renal disease. However, acute rejection (AR) is the major source of failure in renal transplantation. The current best practice for the diagnosis of AR involves renal biopsy, but it is invasive, time­consuming, costly and inconvenient. Sensitive and less invasive detection of AR episodes in renal transplant patients is essential to preserve allograft function. The present study applied isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry to analyze serum protein expression in patients with AR and healthy controls. Overall, 1,399 proteins were identified. Using a cut­off of Q<0.05 and a fold change of >1.2 for the variation in expression, 109 proteins were identified to be differentially expressed between the AR and control groups, 72 of which were upregulated and 37 were downregulated. Several proteins, including properdin, keratin 1, lipoprotein(a) and vitamin D­binding protein, may have roles in the pathogenesis of AR. The present study focused on iTRAQ­based proteomic profiling of serum samples in AR. Insight from the present study may help advance the understanding of the molecular mechanisms of AR and identify potential novel biomarkers of AR for further characterization.


Assuntos
Rejeição de Enxerto/diagnóstico , Falência Renal Crônica/terapia , Transplante de Rim/efeitos adversos , Proteômica/métodos , Adulto , Estudos de Casos e Controles , Cromatografia Líquida , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Rejeição de Enxerto/sangue , Humanos , Queratina-1/sangue , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Properdina/metabolismo , Espectrometria de Massas em Tandem , Transplante Homólogo , Proteína de Ligação a Vitamina D/sangue
15.
Clin Transplant ; 33(10): e13677, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31342552

RESUMO

BACKGROUND: This study aimed to explore the safety of donors with primary central nervous system tumors for kidney and liver transplantations. METHODOLOGY: Clinical data of 29 donors with primary CNS tumors in January 2007 to December 2017, as well as the follow-up data of 16 liver transplant recipients and 46 kidney transplant recipients, were analyzed. According to the risk factors, the high-risk group was classified as Group 1, the low-risk factors were classified as Group 2, and the unknown risk group was classified as Group 3. The incidence of donor-transmitted CNS tumors was calculated and compared. RESULTS: The duration from the diagnosis of 29 donors to donation was 5.67 ± 6.36 months. None of the liver and kidney transplant recipients who were followed up had tumor metastasis. Although the mean survival time of Group 1 was lower than that of Group 2 and Group 3, the Kaplan-Meier curve showed no significant difference in survival time. CONCLUSION: No obvious difference was observed between high-risk and low-risk and unknown risk CNS tumors in terms of the survival rate of transplants and tumor metastasis rate. High-risk CNS tumor donors can be used with the informed consent of recipients after a full evaluation.


Assuntos
Neoplasias do Sistema Nervoso Central/patologia , Transplante de Rim/mortalidade , Transplante de Fígado/mortalidade , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
16.
Oncotarget ; 10(26): 2508-2514, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-31069013

RESUMO

Liver cancer is the second leading cause of cancer mortality worldwide. Safer and more effective diagnostic methods for liver cancer are desirable, and biomarkers represent a potentially alternative method for diagnosis. The present study was designed to identify liver cancer biomarkers. We quantified the changes in serum protein levels between liver transplantation and healthy (control) females using isobaric tags for relative and absolute quantitation (iTRAQ) as well as proteomic analysis. A total of 1399 proteins were identified; of these, three proteins showed significantly different concentrations between the before transplantation group and the control group. These proteins may thus be relevant to liver cancer and constitute potential liver cancer biomarkers.

17.
Mol Clin Oncol ; 7(4): 716-720, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29046803

RESUMO

Sarcoma is one of the most prevalent pediatric tumors and the therapeutic role of chemotherapy has yet to be elucidated. It has been reported that extracts of Longyanshen (Yulangsan) may enhance the sensitivity of drug-resistant cancer cell lines, and improve the immune dysfunction induced by cyclophosphamide (CTX) in mice. The present in vivo study investigated the antitumor effects of Yulangsan polysaccharides (YLSPS) and their interaction with CTX in murine sarcoma 180 (S180)-bearing mice. Immunohistochemistry was used to detect the expression of apoptosis-related proteins. The ultrastructure of sarcoma cells was examined by transmission electron microscopy and the tumor growth rate was determined by measuring the tumor weight. A dose-dependent inhibition of sarcoma growth was observed in S180-bearing mice following administration of YLSPS. In combination with CTX, an additive antitumor effect was obtained, which was accompanied by amelioration of immune function. YLSPS also potentiated the tumor suppression effect of CTX while avoiding cytotoxicity against immune cells. YLSPS inhibited sarcoma growth in S180-bearing mice through the induction of apoptosis in S180 sarcoma cells. YLSPS also attenuated CTX-induced cytotoxicity to the immune system while potentiating the tumor suppression effect. These results provide additional information regarding combination therapy with YLSPS and chemotherapy for the treatment of sarcoma.

18.
Oncotarget ; 7(34): 55529-55542, 2016 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-27487125

RESUMO

Since the tumor-oriented homing capacity of mesenchymal stem cells (MSCs) was discovered, MSCs have attracted great interest in the research field of cancer therapy mainly focused on their use as carries for anticancer agents. Differing from DNA-based vectors, the use of mRNA-based antituor gene delivery benefits from readily transfection and mutagenesis-free. However, it is essential to verify if mRNA transfection interferes with MSCs' tropism and their antitumor properties. TRAIL- and PTEN-mRNAs were synthesized and studied in an in vitro model of MSC-mediated indirect co-culture with DBTRG human glioma cells. The expression of TRAIL and PTEN in transfected MSCs was verified by immunoblotting analysis, and the migration ability of MSCs after anticancer gene transfection was demonstrated using transwell co-cultures. The viability of DBTRG cells was determined with bioluminescence, live/dead staining and real time cell analyzer. An in vivo model of DBTRG cell-derived xenografted tumors was used to verify the antitumor effects of TRAIL- and PTEN-engineered MSCs. With regard to the effect of mRNA transfection on MSCs' migration toward glioma cells, an enhanced migration rate was observed with MSCs transfected with all tested mRNAs compared to non-transfected MSCs (p<0.05). TRAIL- and PTEN-mRNA-induced cytotoxicity of DBTRG glioma cells was proportionally correlated with the ratio of conditioned medium from transfected MSCs. A synergistic action of TRAIL and PTEN was demonstrated in the current co-culture model. The immunoblotting analysis revealed the apoptotic nature of the cells death in the present study. The growth of the xenografted tumors was significantly inhibited by the application of MSCPTEN or MSCTRAIL/PTEN on day 14 and MSCTRAIL on day 28 (p<0.05). The results suggested that anticancer gene-bearing mRNAs synthesized in vitro are capable of being applied for MSC-mediated anticancer modality. This study provides an experimental base for further clinical anticancer studies using synthesized mRNAs.


Assuntos
Neoplasias Encefálicas/terapia , Terapia Genética/métodos , Glioma/terapia , Células-Tronco Mesenquimais/fisiologia , PTEN Fosfo-Hidrolase/genética , RNA Mensageiro/genética , Ligante Indutor de Apoptose Relacionado a TNF/genética , Animais , Neoplasias Encefálicas/patologia , Movimento Celular , Feminino , Glioma/patologia , Humanos , Camundongos , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Exp Ther Med ; 11(3): 988-992, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26998025

RESUMO

Effective use of all available donated organs is critical, in order to meet the increasing demand for transplants. The present study explored liver transplantation with livers that were donated following cardiac death (DCD). According to the guidelines established by The Red Cross Society of China, 42 DCD organs were procured. Selected donors were treated with extracorporeal membrane oxygenation (ECMO) prior to the organ retrieval. The present single-center study included 6 liver transplantations of DCD organs (5 liver transplants and 1 liver-kidney combined transplant). All 6 recipients had a successful recovery without significant complications. The serum alanine transaminase, total bilirubin and international normalized ratio returned to the normal levels within a short period of time following transplantation, and the liver function remained normal during the follow-up period, which lasted up to 24 months. The present report demonstrated the feasibility of orthotopic liver transplantation using DCD livers. The pre-conditioning DCD donors and optimization of the recipient's condition using ECMO, played a crucial role in ensuring the success of transplantation.

20.
Zhonghua Bing Li Xue Za Zhi ; 45(2): 91-6, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26879429

RESUMO

OBJECTIVE: To study the clinical and histopathologic features of post-transplant kidney biopsy tissues from pediatric C-III donors. METHODS: The clinical and pathologic features of 20 cases (22 case-times) of renal transplant biopsies from pediatric cadaveric donors were analyzed by light microscopy and immunohistochemistry according to the Banff system of working classification of renal allograft pathology. Biopsies were compared to those from adult C-III donors and adult cadaveric donors. RESULTS: Sixteen cases (72.7%) showed renal allograft drug toxicity damage by Tacrolimus, seven cases (31.8%) showed degeneration and necrosis of renal tubular epithelial cells, four cases (18.2%) showed T cell-mediated acute rejection and six cases (27.3%) showed renal interstitial inflammation. There were two cases (9.1%) of renal dysplasia and one case (4.5%) of renal infarction. There was insufficient evidence for diagnosis of renal allograft nephropathy. Compared to post-transplant kidney from adult C-III donors, the proportion of drug toxicity damage was higher (P<0.05). Compared to post-transplant kidney from adult cadavers, the proportions of drug toxicity damage, degeneration and necrosis of renal tubular epithelial cells were higher (P<0.05) while the proportion of acute rejection was lower (P<0.05). CONCLUSIONS: The pathologic changes in the post-transplant kidneys from pediatric donors are different from those from adult donors. Optimal long-term outcome can be accomplished by effective treatment based on timely or procedural biopsy.


Assuntos
Transplante de Rim , Rim/patologia , Adulto , Fatores Etários , Biópsia , Cadáver , Criança , Rejeição de Enxerto/patologia , Humanos , Imuno-Histoquímica , Imunossupressores/efeitos adversos , Infarto/patologia , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Necrose , Tacrolimo/efeitos adversos , Transplante Homólogo , Resultado do Tratamento
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