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Hospital-acquired pressure ulcers (HAPUs) are still an important worldwide issue related to the safety and quality of patient care, which are among the top five adverse events reported. Patients who develop HAPUs have longer stays in the hospital than necessary, are at a greater risk of infections, and are more likely to die. Surgical patients are prone to developing PUs because they often remain immobile for extended periods of time, and their surgical procedures may limit the flow of blood oxygen and nutrition and lead to a decrease in muscle tone. Mesenchymal stem cells (MSCs) represent an attractive stem cell source for tissue regeneration in clinical applications, which have been demonstrated to improve wound healing through re-epithelialization, increased angiogenesis, and granulation tissue formation. Here, we present the case of an emergency surgical patient who developed an ulcer on the right heel during hospitalization. The human umbilical cord Wharton's jelly-derived MSCs (WJ-MSCs) re-suspended in platelet-rich plasma (PRP) were injected into ulcer margins. Four days after the WJ-MSC application, the patient showed progressive healing of the PU. From days 4 to 33, granulation tissue formation and re-epithelialization were clearly observed. The ulcer was almost healed completely on day 47, and the pain in the patient's wound area also decreased. Thus, intradermal transplantation of WJ-MSCs and PRP was safe and effective for treatment in patients with pressure ulcers. WJ-MSCs, together with PRP, may offer a promising treatment option for wound healing.
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Osteosarcoma is an aggressive form of bone cancer and affects the health in children and adolescents. Although conventional treatment improves the osteosarcoma survival, some patients have metastasis and drug resistance, leading to a worse prognosis. Therefore, it is necessary to explore the molecular mechanism of osteosarcoma occurrence and progression, which could discover the novel treatment for osteosarcoma. Long noncoding RNAs (lncRNAs) have been reported to regulate osteosarcoma occurrence and malignant progression. LncRNA HOXA-AS3 facilitates the tumorigenesis and progression in a variety of human cancers. However, the underlying mechanism of lncRNA HOXA-AS3-induced oncogenesis is poorly determined in osteosarcoma. To address this point, we utilized several cellular biological strategies and molecular approaches to explore the biological functions and mechanisms of lncRNA HOXA-AS3 in osteosarcoma cells. We found that lncRNA HOXA-AS3 facilitates cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma. In conclusion, lncRNA HOXA-AS3 could be a promising target for osteosarcoma treatment.
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Neoplasias Ósseas , Proliferação de Células , Fatores de Transcrição Forkhead , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Proteínas Repressoras , Osteossarcoma/genética , Osteossarcoma/patologia , Osteossarcoma/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Invasividade Neoplásica , Movimento Celular/genéticaRESUMO
Background: The status of the sentinel lymph nodes (SLNs) was an important prognostic factor in varies cancers. A one-step nucleic acid amplification (OSNA) assay, a molecular-based whole-node analysis method based on CK19 mRNA copy number, was developed to diagnose lymph node metastases. We aimed to evaluate the value of OSNA for the diagnosis of sentinel lymph node metastasis in CK19 positive cancers. CK19 mRNA and protein expression for pan-caner analysis were obtained from TCGA and the Human protein atlas database. Methods: Two researchers independently searched the PubMed, Cochrane Library and Web of Science databases for qualified articles published before December 1, 2023. A meta-analysis was performed using MetaDisc and STATA. Risk bias and quality assessments of the included studies were evaluated, and a subgroup analysis was performed. Ten cancer types were found to be CK19 positively expressed and 7 of 10 had been reported to use OSNA for SLN detection. Results: After literature review, there were 61 articles included in the meta-analysis, which consisted of 7115 patients with 18007 sentinel lymph nodes. The pooled sensitivity and specificity of OSNA were 0.87 and 0.95 in overall patients. Moreover, we found the background CK19 expression in normal tissue affected the diagnostic accuracy of OSNA. In breast cancer, we performed subgroup analysis. OSNA exhibited to be a stable method across different population groups and various medical centers. In addition, when 250 copies/µl was chosen as the cutoff point of CK19 mRNA, there were a relatively higher sensitivity and AUC in detecting SLN micro-metastasis than 5000 copies/µl. Discussion: OSNA can predict the occurrence of SLN metastasis accurately in CK19 positive cancers, especially in breast cancer, colorectal cancer, lung cancer, gastric cancer and endometrial cancer. Our study warrants future studies investigating the clinical application of OSNA in pancreatic, ovarian and bladder cancers.
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Urea electrolysis is an appealing topic for hydrogen production due to its ability to extract hydrogen at a lower potential. However, it is plagued by sluggish kinetics and noble-metal catalyst requirements. Herein, we developed nickel-iron-layered double hydroxide (NiFe-LDH) nanolayers with abundant oxygen vacancies (OV) via synergistically etching nickel foam with Fe3+ and Cl- ions, enabling the efficient conversion of urea into H2 and N2. The synthesized OV-NiFe-LDH exhibits a lower potential (1.30 vs. reversible hydrogen electrode, RHE) for achieving 10 mA cm-2 in the urea oxidation reaction (UOR), surpassing most recently reported Ni-based electrodes. OV provides favorable conductivity and a large surface area, which results in a 4.1-fold in electron transport and a 5.1-fold increase in catalyst reactive sites. Density Functional Theory (DFT) calculations indicate that OV can lower the adsorption energy of urea, and enhance the bonding strength of *CONHNH, giving rise to improved UOR. This study provides a viable path toward economical and efficient production of high-purity hydrogen.
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Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide. For diverse disease conditions, the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) isolated from the human UC have the capacity for self-renewal and multilineage differentiation. Moreover, in recent years, these cells have been demonstrated to have unique advantages in the treatment of lung diseases. We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases, including coronavirus disease 2019, acute respiratory distress syndrome, bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis. In this review, we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application. Moreover, the underlying molecular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth. In brief, this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.
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More and more evidence shows that long non-coding RNA (lncRNA) plays an important role in the biological behavior of many kinds of malignant tumors, but the specific function of lncRNA Linc00657 in cervical cancer is still unknown. The purpose of this study is to explore the effect of Linc00657 on the malignant progression of cervical cancer and its potential mechanism. In two kinds of cervical cancer cell lines and normal cervical epithelial cells, qRT-PCR showed increased expression of Linc00657 in cervical cancer cells. Through MTT, clone formation test, flow cytometry, wound healing test and Transwell test, it has been found that overexpression of Linc00657 could promote the proliferation,migration and invasion of cervical cancer cellsï¼and inhibit apoptosis. Through the StarBase database, it was found that there may be a mutual regulatory relationship between Linc00657 and Skp2, and Skp2 may be the downstream target of Linc00657. QRT-PCR detection confirmed that the expression of Skp2 was increased in cervical cancer cells with overexpression of Linc00657. TIMER2 database found that Skp2 was associated with lipid metabolic enzymes and immune cell infiltration. It was found that Linc00657 knockdown inhibited tumor growth and metastasis and inhibited the expression of Skp2 in vivo. In short, our research shows that Linc00657 has carcinogenic properties in cervical cancer, and LINC00657 promotes the occurrence of cervical cancer by up-regulating the expression of Skp2. We predict that Linc00657/mir30s/Skp2 axis plays a role in the malignant progression of cervical cancer. In addition, Skp2 may participate in cancer immune response and promote lymph node metastasis of cervical cancer through lipid reprogramming. These findings also provide promising targets for the diagnosis and treatment of cervical cancer.
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MicroRNAs , RNA Longo não Codificante , Neoplasias do Colo do Útero , Feminino , Humanos , Linhagem Celular Tumoral , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Carcinogênese/genética , Lipídeos , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Movimento Celular/genética , MicroRNAs/metabolismo , Microambiente Tumoral/genéticaRESUMO
Environmental pollutants, such as quinoline (QN) and 4-methylquinoline (4-MeQ), may be genotoxic and carcinogenic. Earlier studies, including in vitro genotoxicity tests, indicated that 4-MeQ is more mutagenic than QN. However, we hypothesized that the methyl group of 4-MeQ favors detoxication over bioactivation, and this factor may be overlooked in in vitro tests that do not incorporate supplementation with cofactors for enzymes that catalyze conjugation reactions. We used human induced hepatocyte cells (hiHeps), which express such enzymes, and compared the genotoxicity of 4-MeQ and QN. We also carried out an in vivo micronucleus (MN) test in rat liver, since 4-MeQ is not genotoxic in rodent bone marrow. In the Ames test and the Tk gene mutation assay, with rat S9 activation, 4-MeQ was more mutagenic than QN. However, QN induced significantly higher MN frequencies in hiHeps and rat liver than did 4-MeQ. Furthermore, QN upregulated genotoxicity marker genes much more than did 4-MeQ. We also investigated the roles of two important detoxication enzymes, UDP-glucuronosyltransferases (UGTs) and cytosolic sulfotransferases (SULTs). When hiHeps were preincubated with hesperetin (UGT inhibitor) and 2,6-dichloro-4-nitrophenol (SULT inhibitor), MN frequencies were elevated approximately 1.5-fold for 4-MeQ, whereas no significant effects were seen for QN. This study shows that QN is more genotoxic than 4-MeQ, when the roles of SULTs and UGTs in detoxication are considered and our results may improve understanding the structure-activity relationships of quinoline derivatives.
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Mutagênicos , Quinolinas , Animais , Humanos , Ratos , Núcleo Celular , Glucuronosiltransferase , Fígado , Quinolinas/toxicidadeRESUMO
Osteosarcoma often occurs in children and adolescents and affects their health. The survival rate of osteosarcoma patients is unsatisfactory due to the lack of early detection and metastasis development and drug resistance. Hence, dissection of molecular insight into osteosarcoma initiation and progression is pivotal to provide the new therapeutic strategy. In recent years, long noncoding RNAs (lncRNAs) have burst into stage in osteosarcoma development and malignant behaviors. LncRNA SCAMP1 has been discovered to play an essential role in carcinogenesis and progression. However, the mechanisms of lncRNA SCAMP1-involved tumorigenesis have not been reported in human osteosarcoma. In this study, we utilized multiple cellular biological approaches to determine the function of lncRNA SCAMP1 in osteosarcoma cells. Moreover, we performed several molecular biological approaches to define the mechanism by which lncRNA SCAMP1 regulated cell viability and invasion in osteosarcoma. We dissected that lncRNA SCAMP1 promoted progression of osteosarcoma via modulation of miR-26a-5p/ZEB2 axis. In conclusion, targeting lncRNA SCAMP1 and its downstream targets, miR-26a-5p and ZEB2, might be a useful approach for osteosarcoma therapy.
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H2S and CO2 are the main impurities in raw natural gas, which needs to be purified before use. However, the comprehensive utilization of H2S and CO2 has been ignored. Herein, we proposed a fully resource-based method to convert toxic gas H2S and greenhouse gas CO2 synchronously into CO and elemental S by using a novel electrochemical reactor. The special designs include that, in the anodic chamber, H2S was oxidized rapidly to S based on the I-/I3- cyclic redox system to avoid anode passivation. On the other hand, in the cathodic chamber, CO2 was rapidly and selectively reduced to CO based on a porous carbon gas diffusion electrode (GDE) modified with polytetrafluoroethylene and cobalt phthalocyanine (CoPc). A high Faraday efficiency (>95%) toward CO was achieved due to the enhanced mass transfer of CO2 on the GDE and the presence of the selective CoPc catalyst. The maximum energy efficiency of the system was more than 72.41% with a current density of over 50 mA/cm2, which was 12.5 times higher than what was previously reported on the H2S treatment system. The yields of S and CO were 24.94 mg·cm-2·h-1 and 19.93 mL·cm-2·h-1, respectively. A model analysis determined that the operation cost of the synchronous utilization of H2S and CO2 method was slightly lower than that of the single utilization of H2S in the existing natural gas purification technology. Overall, this paper provides efficient and simultaneous conversion of H2S and CO2 into S and CO.
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Dióxido de Carbono , Gás Natural , Catálise , Eletrodos , OxirreduçãoRESUMO
The repeated-dose liver micronucleus (RDLMN) assay is a novel method for detecting genotoxic chemicals. Two carcinogens methyl carbamate (MC) and 1,3-propane sultone (PS) were evaluated for the liver micronucleus in a 14-day repeated-dose study with Crl: CD (SD) IGS rats. Additionally, micronucleated reticulocytes (MN-RET) in peripheral blood and DNA damage (alkaline comet assay) in the liver were also assessed in the same animals. Ten groups of five male Crl: CD (SD) IGS rats were treated once daily with MC (300, 600 or 1200 mg/kg/day), PS (37.5, 75 or 150 mg/kg/day), negative control or three positive controls by oral gavage for 15 days. Blood samples were collected at 3 h after the last administration for determining MN-RET frequencies (%MN-RET), and the livers were sampled for determining the frequency of micronuclei and DNA damage. MC was negative in the comet assay, liver micronucleus assay and reticulocyte micronucleus assay, while PS was positive in all three assays. These results are consistent with the previous genotoxic findings of MC and PS. Therefore, the liver micronucleus assay can be effectively integrated into repeated-dose studies in animals. Moreover, integration of multiple genotoxicity end points into one study can reduce the number of animals, boost the experimental efficiency, and provides a comprehensive evaluation of the genotoxic potential of chemicals.
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Carbamatos/toxicidade , Núcleo Celular/efeitos dos fármacos , Fígado/efeitos dos fármacos , Reticulócitos/efeitos dos fármacos , Tiofenos/toxicidade , Animais , Carcinógenos/toxicidade , Aberrações Cromossômicas , Ensaio Cometa/métodos , Dano ao DNA , Relação Dose-Resposta a Droga , Esquema de Medicação , Masculino , Testes para Micronúcleos/métodos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Sodium cantharidinate/vitamin B6â(SC/VB6) injection, a famous insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of SC/VB6 injection on survival, liver function, immune function, and quality of life (QoL) in patients with HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of SC/VB6 for patients with HCC were searched from ten electronic databases including PubMed, Google Scholar, Cochrane Library, Excerpt Medica Database (Embase), Medline, Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ), and Wanfang Database. Papers in Chinese or English published from January 2000 to July 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall survival (OS), QoL, liver function, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the clinical trials was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of SC/VB6 on survival, liver function, immune function, and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070121.
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Cantaridina/análogos & derivados , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/patologia , Vitamina B 6/farmacologia , Complexo Vitamínico B/farmacologia , Cantaridina/administração & dosagem , Cantaridina/farmacologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/psicologia , China/epidemiologia , Quimioterapia Combinada/métodos , Humanos , Sistema Imunitário/efeitos dos fármacos , Injeções/métodos , Fígado/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Sobrevida , Resultado do Tratamento , Vitamina B 6/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Metanálise como AssuntoRESUMO
BACKGROUND: Brucea javanica oil emulsion injection (BJOEI) has been widely applied as a promising adjunctive drug for colorectal carcinoma (CRC). However, the exact effects and safety of BJOEI remains controversial. In this study, we aimed to summarize the efficacy and safety of BJOEI for the treatment of advanced CRC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. METHODS: Eligible prospective controlled clinical trials were searched from PubMed, Cochrane Library, Google Scholar, Medline, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese BioMedical Database (CBM), China Scientific Journal Database (VIP), China National Knowledge Infrastructure (CNKI) and Wanfang Database. Papers in English or Chinese published from January 2000 to May 2020 will be included without any restrictions. The clinical outcomes including therapeutic effects, quality of life (QoL), immune function and adverse events, were systematically evaluated.Study selection and data extraction will be performed independently by 2 reviewers. Review Manager 5.3 and Stata 14.0 were used for data analysis, and a fixed or random-effect model will be used depending upon the heterogeneity observed between trials. Subgroup and meta-regression analysis will be carried out depending on the availability of sufficient data. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: Our study will draw an objective conclusion of the effects and safety of BJOEI for advanced CRC, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for CRC patients.INPLASY registration number: INPLASY202060014.
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Brucea/efeitos adversos , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/tratamento farmacológico , Emulsões/administração & dosagem , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Colorretais/psicologia , Emulsões/uso terapêutico , Feminino , Humanos , Injeções/métodos , Masculino , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento , Metanálise como AssuntoRESUMO
The novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency since patients were first detected in Wuhan, China. Thus far, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. The immune system and inflammation are proposed to play a central role in COVID-19 pathogenesis. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. Intravenous infusion of MSCs has shown promising results in COVID-19 treatment. Here, we report a case of a severe COVID-19 patient treated with human umbilical cord Wharton's jelly-derived MSCs (hWJCs) from a healthy donor in Liaocheng People's Hospital, China, from February 24, 2020. The pulmonary function and symptoms of the patient with COVID-19 pneumonia was significantly improved in 2 days after hWJC transplantation, and recovered and discharged in 7 days after treatment. After treatment, the percentage and counts of lymphocyte subsets (CD3+, CD4+, and CD8+ T cell) were increased, and the level of IL-6, TNF-α, and C-reactive protein is significantly decreased after hWJC treatment. Thus, the intravenous transplantation of hWJCs was safe and effective for the treatment of patients with COVID-19 pneumonia, especially for the patients in a critically severe condition. This report highlights the potential of hWJC infusions as an effective treatment for COVID-19 pneumonia.
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Betacoronavirus/patogenicidade , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Pneumonia Viral/terapia , Betacoronavirus/genética , Proteína C-Reativa/imunologia , Proteína C-Reativa/metabolismo , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Humanos , Imunomodulação , Infusões Intravenosas , Interleucina-6/sangue , Interleucina-6/imunologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/virologia , Masculino , Células-Tronco Mesenquimais/imunologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , SARS-CoV-2 , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia , Cordão Umbilical/citologia , Cordão Umbilical/imunologia , Geleia de Wharton/citologia , Geleia de Wharton/imunologia , Tratamento Farmacológico da COVID-19RESUMO
A newly developed in vivo Pig-a gene mutation assay displays great potential for integration into genotoxicity tests. To obtain more evidence for application of the Pig-a assay, we integrated this assay, micronucleus test in peripheral blood (MN-pb test) and bone marrow (MN-bm test), as well as a Comet assay into a transgenic RasH2 mice carcinogenicity study. Fourteen male RasH2 mice and five wild-type (WT) mice were treated with a strong mutagen aristolochic acid I at a dose of 5 mg/kg/day for 4 consecutive weeks. Mice recovered in 5 weeks. Peripheral bloods were collected for Pig-a assay, MN-pb test, and Comet assay at several time points, while bone marrow and target organs were harvested for the MN-bm test and pathological diagnosis after mice were euthanized. Finally, 13 of the 14 RasH2 mice developed squamous cell carcinomas in the forestomach, while there were no carcinomas in the WT mice. Pig-a mutant frequencies (MFs) consecutively increased throughout the study to a maximum value of approximately 63-fold more than background. These frequencies were relative to the incidence, size, and malignant degree of tumors. Micronucleated reticulocytes increased from Day 1 to Day 49, before returning to background levels. No positive responses were observed in either the MN-bm test or the Comet assay. Results suggested that, when compared with the other two tests, the Pig-a assay persistently contributed to sustaining MFs, enhanced detection sensitivity due to the accumulation of Pig-a mutations, and demonstrated better predictability for tumorigenicity. Environ. Mol. Mutagen. 61:266-275, 2020. © 2019 Wiley Periodicals, Inc.
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Ácidos Aristolóquicos/toxicidade , Carcinógenos/toxicidade , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Carcinogênese/patologia , Ensaio Cometa/métodos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos/métodosRESUMO
A series of genotoxicity assessments were conducted on male Sprague Dawley rats treated with Auramine O (AO) to establish a multiple-endpoint assay. The rat liver micronucleus assay, in combination with the comet assay, peripheral blood micronucleus assay, and erythrocyte Pig-a assay in the same experiment, comprehensively assess the genotoxicity of AO. Rats were orally exposed to 0, 100, 200, or 400â¯mg/kg/day AO for 15 consecutive days. The blood was sampled on Days -1 and 15 for the erythrocyte Pig-a assay and peripheral blood micronucleus assay. Livers were sampled on Day 15 for the liver micronucleus assay and comet assay. Based on the liver micronucleus assay and liver comet assay, AO induced a significant dose-related increase of micronucleated hepatocyte frequencies, and tail DNA percentages, respectively in the middle- and high-dose groups. On the blood micronucleus test and Pig-a assay, no significant increases were observed for the micronucleated reticulocyte frequencies, mutant erythrocyte frequencies (RBCCD59-) or mutant reticulocyte frequencies (RETCD59-) at any of the time points studied. In conclusion, using a multiple-endpoint genotoxicity assay method can reduce the number of experimental animals, boost the efficiency of the experiment, and improve the accuracy of investigations of genotoxicity.
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Benzofenoneídio/toxicidade , Carcinógenos/toxicidade , Ensaio Cometa , Proteínas de Membrana/genética , Testes para Micronúcleos , Ativação Metabólica , Animais , Relação Dose-Resposta a Droga , Determinação de Ponto Final , Eritrócitos/efeitos dos fármacos , Eritrócitos/enzimologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/ultraestrutura , Masculino , Microssomos Hepáticos/enzimologia , Testes de Mutagenicidade , Mutação , Estudo de Prova de Conceito , Ratos , Ratos Sprague-Dawley , Reticulócitos/efeitos dos fármacos , Reticulócitos/ultraestruturaRESUMO
1-Chloro-2-hydroxy-3-butene (CHB) is a possible metabolite of 1,3-butadiene, a carcinogenic air pollutant. To demonstrate its formation in vivo, it is desirable to develop a practical biomarker and the corresponding analysis method. CHB can undergo alcohol dehydrogenase- and cytochromes P450 enzymes (P450)-mediated oxidation to yield 1-chloro-3-buten-2-one (CBO), which readily forms glutathione conjugates. We hypothesized that CBO-derived mercapturic acids, which are the expected biotransformed products of CBO-glutathione conjugates, could be used as CHB biomarkers. Thus, in the present study, we investigated the in vivo biotransformation of CHB into CBO-derived mercapturic acids. Because the reaction of CBO with N-acetyl-l-cysteine yields two products, 1,4-bis(N-acetyl-S-cysteinyl)-2-butanone (NC1) and 1-chloro-4-(N-acetyl-S-cysteinyl)-2-butanone (NC2), we first developed an isotope dilution LC/ESI--MS-MS method to quantitate urinary NC1 and NC2, and then determined their concentrations in urine of C57BL/6 mice and Sprague-Dawley rats administered CHB. Since no NC2 was detected in samples, the LC/ESI--MS-MS method was optimized specifically for NC1. NC1 was enriched through solid phase extraction with the recovery being 75-82%. The limits of detection and quantitation were 6.8 and 34 fmol/0.1â¯mL for mouse urine, and 4.5 and 7.1 fmol/0.1â¯mL for rat urine, respectively. In urine of animals before CHB administration, no NC1 was detected; in mice administered CHB at 10 and 30â¯mg/kg, and rats at 5 and 15â¯mg/kg, NC1 was detected and its concentrations in urine from animals given higher doses were 3-6 fold higher than those given lower doses. Moreover, the NC1 concentrations in urine during 0-8â¯h were 4-6 fold and 10-11 fold higher than those during 8-24â¯h for mice and rats, respectively. The results demonstrated that CHB could be in vivo biotransformed into NC1, which could be used as a practical CHB biomarker.
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Biomarcadores/urina , Butadienos/metabolismo , Butanóis/metabolismo , Espectrometria de Massas em Tandem , Acetilcisteína/química , Poluentes Atmosféricos/química , Animais , Butadienos/química , Butanóis/química , Cromatografia Líquida de Alta Pressão , Marcação por Isótopo , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Immunotherapy based on cytokine-induced killer cells or combination of dendritic cells and cytokine-induced killer cells (CIK/DC-CIK) showed promising clinical outcomes for treating esophageal cancer (EC). However, the clinical benefit varies among previous studies. Therefore, it is necessary to systematically evaluate the curative efficacy and safety of CIK/DC-CIK immunotherapy as an adjuvant therapy for conventional therapeutic strategies in the treatment of EC. MATERIALS AND METHODS: Clinical trials published before October 2016 and reporting CIK/DC-CIK immunotherapy treatment responses or safety for EC were searched in Cochrane Library, EMBASE, PubMed, Wanfang and China National Knowledge Internet databases. Research quality and heterogeneity were evaluated before analysis, and pooled analyses were performed using random- or fixed-effect models. RESULTS: This research covered 11 trials including 994 EC patients. Results of this meta-analysis indicated that compared with conventional therapy, the combination of conventional therapy with CIK/DC-CIK immunotherapy significantly prolonged the 1-year overall survival (OS) rate, overall response rate (ORR) and disease control rate (DCR) (1-year OS: P=0.0005; ORR and DCR: P<0.00001). Patients with combination therapy also showed significantly improved quality of life (QoL) (P=0.02). After CIK/DC-CIK immunotherapy, lymphocyte percentages of CD3+ and CD3-CD56+ subsets (P<0.01) and cytokines levels of IFN-γ, -2, TNF-α and IL-12 (P<0.00001) were significantly increased, and the percentage of cluster of differentiation (CD)4+CD25+CD127- subset was significantly decreased, whereas analysis of CD4+, CD8+, CD4+/CD8+ and CD3+CD56+ did not show significant difference (P>0.05). CONCLUSION: The combination of CIK/DC-CIK immunotherapy and conventional therapy is safe and markedly prolongs survival time, enhances immune function and improves the treatment efficacy for EC.