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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 220-235, 2024 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38755718

RESUMO

OBJECTIVES: The mouse kidney transplantation model presents challenges in terms of surgical difficulty and low success rate, making it difficult to master. This study aims to provide a crucial model for transplantation immunology research by modifying and developing novel techniques for mouse kidney transplantation. METHODS: A total of 57 pairs of mice were used to establish and compare the modified and innovative surgical techniques for mouse kidney transplantation. Three different surgical models were established, including the abdominal suture technique for orthotopic kidney transplantation, the abdominal cuff technique for orthotopic kidney transplantation, and the cervical cuff technique for ectopic kidney transplantation. BALB/c or C57BL/6 male mice, aged 8 to 12 weeks and weighed 20 to 25 g with specified pathogen free-grade were served as the donor mice or the recipient mice. The surgical technique characteristics, key surgical times, complications, and pathological examination in the early postoperative period were summarized and compared. RESULTS: Three different surgical models of mouse kidney transplantation were successfully established. The comparison of warm ischemic time for the 3 groups of mice showed no statistical significance (P=0.510 4). The abdominal suture group had the shortest total operation time of the donor compared with the abdominal cuff group and the cervical cuff group [(18.3±3.6) min vs (26.2±4.7) min and (22.8±2.5) min; both P<0.000 1]. There was a significant difference in cold ischemia time among the 3 groups (all P<0.000 1), with (60.8±4.1) min in the cervical cuff group, (43.3±5.0) min in the abdominal suture group, and (88.8±6.7) min in the abdominal cuff group. Due to different anastomosis methods, the cervical cuff group had the shortest time [(17.6±2.7) min], whereas the abdominal cuff group had the longest time [(38.8±5.4) min]. The total operation time for the recipients showed significant differences (P<0.000 1), with the abdominal suture group having the shortest time [(44.0±6.9) min], followed by the cervical cuff group [(64.1±5.2) min], and the abdominal cuff group [(80.0±6.0) min] being the longest. In the 32 mice of the abdominal suture group, there were 6 with intraoperative bleeding, including 1 arterial intimal injury bleeding and 5 with bleeding after vessel opening. Six mice had ureteral complications, including ureteral bladder anastomotic stenosis, necrosis, and renal pelvis dilation. Two mice had postoperative abdominal infections. In the abdominal cuff group, there was no intraoperative bleeding, but 6 mice showed mild arterial stenosis and 5 showed venous stenosis, 4 arterial injury, 4 arterial thrombosis, and 2 ureteral complications. No postoperative infections occurred in the mice. In the cervical cuff group, no intraoperative bleeding, arterial intimal injury, arterial/venous stenosis, or thrombosis were found in 13 mice. Five mice had ureteral complications, including ureteral necrosis and infection, which were the main complications in the cervical cuff group. The renal function in mice of the 3 groups remained stable 7 days after surgery. Hematoxylin and eosin staining and periodic acid-Schiff staining showed no significant differences in terms of acute rejection among the 3 surgical methods (all P>0.05). CONCLUSIONS: All 3 surgical methods are able to successfully establish mouse kidney transplantation models, with no significant differences observed in the short-term graft survival and acute rejection. The modified abdominal suture technique and abdominal cuff technique have their respective advantages in research applications. The novel cervical cuff technique for ectopic kidney transplantation model is relatively simple to be prepared and causes less trauma to the mice, providing more options for studies involving xenotransplantation, secondary transplantation, and local lymphatic drainage. However, the difficulty in harvesting the donor kidney and the high incidence of ureteral infections need further validation in long-term survival. This study holds important reference value for choosing the type of mouse kidney transplantation model for different research needs.


Assuntos
Transplante de Rim , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Animais , Camundongos , Transplante de Rim/métodos , Transplante de Rim/efeitos adversos , Masculino , Modelos Animais
2.
Eur J Immunol ; 53(10): e2250071, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37379419

RESUMO

Disulfide bond A oxidoreductase-like protein (DsbA-L) drives acute kidney injury (AKI) by directly upregulating the expression of voltage-dependent anion-selective channels in proximal tubular cells. However, the role of DsbA-L in immune cells remains unclear. In this study, we used an LPS-induced AKI mouse model to assess the hypothesis that DsbA-L deletion attenuates LPS-induced AKI and explore the potential mechanism of DsbA-L action. After 24 hours of LPS exposure, the DsbA-L knockout group exhibited lower serum creatinine levels compared to the WT group. Furthermore, peripheral levels of the inflammatory cytokine IL-6 were decreased. Transcriptomic data analysis revealed a significant down-regulation in the IL-17 and tumor necrosis factor pathways in DsbA-L knockout mice following LPS induction. Metabolomic analysis suggested that arginine metabolism was significantly different between the WT and DsbA-L knockout groups after LPS treatment. Notably, the M1 polarization of macrophages in the kidneys of DsbA-L knockout AKI mice was significantly reduced. Expression of the transcription factors NF-κB and AP-1 was downregulated after DsbA-L knockout. Our results suggest that DsbA-L regulates LPS-mediated oxidative stress, promotes M1 polarization of macrophages, and induces expression of inflammatory factors via the NF-κB/AP-1 pathway.


Assuntos
Injúria Renal Aguda , NF-kappa B , Animais , Camundongos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Rim/patologia , Lipopolissacarídeos/farmacologia , Macrófagos , NF-kappa B/metabolismo , Fator de Transcrição AP-1
3.
Oncogene ; 42(7): 530-540, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36539569

RESUMO

Appendectomy impacts the homeostasis of gut microbiome in patients. We aimed to study the role of appendectomy in colorectal cancer (CRC) risk through causing gut microbial dysbiosis. Population-based longitudinal study (cohort 1, n = 129,155) showed a 73.0% increase in CRC risk among appendectomy cases throughout 20 years follow-up (Adjusted sub-distribution hazard ratio (SHR) 1.73, 95% CI 1.49-2.01, P < 0.001). Shotgun metagenomic sequencing was performed on fecal samples from cohort 2 (n = 314). Gut microbial dysbiosis in appendectomy subjects was observed with significant enrichment of 7 CRC-promoting bacteria (Bacteroides vulgatus, Bacteroides fragilis, Veillonella dispar, Prevotella ruminicola, Prevotella fucsa, Prevotella dentalis, Prevotella denticola) and depletion of 5 beneficial commensals (Blautia sp YL58, Enterococcus hirae, Lachnospiraceae bacterium Choco86, Collinsella aerofaciens, Blautia sp SC05B48). Microbial network analysis showed increased correlation strengths among enriched bacteria and their enriched oncogenic pathways in appendectomy subjects compared to controls. Of which, B. fragilis was the centrality in the network of the enriched bacteria. We further confirmed that appendectomy promoted colorectal tumorigenesis in mice by causing gut microbial dysbiosis and impaired intestinal barrier function. Collectively, this study revealed appendectomy-induced microbial dysbiosis characterized by enriched CRC-promoting bacteria and depleted beneficial commensals, signifying that the gut microbiome may play a crucial role in CRC development induced by appendectomy.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Animais , Camundongos , Microbioma Gastrointestinal/genética , Disbiose/microbiologia , Apendicectomia/efeitos adversos , Estudos Longitudinais , Neoplasias Colorretais/genética , Neoplasias Colorretais/microbiologia
4.
Chemosphere ; 308(Pt 1): 136098, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35995188

RESUMO

Oxytetracycline and sulfadiazine were widely used and they entered the environment through various channels such as domestic sewage, medical wastewater and agricultural wastewater, causing significant ecological risk. To determine the effects of different antibiotic concentrations on submerged macrophytes, Vallisneria natans was exposed to solutions containing different concentrations of oxytetracycline and sulfadiazine (0.1 mg/L、1 mg/L、10 mg/L、50 mg/L). After 20-days exposure, we found that 10 mg/L groups had a significant effect on Vallisneria natans. Under high antibiotic concentrations, the growth of Vallisneria natans was inhibited, chloroplasts were deformed, the chlorophyll content was reduced, and antioxidant enzyme activities, such as superoxide dismutase and glutathione, were increased. There was no significant difference between the control group and groups with low antibiotic concentrations (≤1 mg/L). The N-acyl-l-homoserine lactone concentration tended to increase with increasing antibiotic concentrations. The presence of antibiotics also affected the microbial community structure of biofilms on the submerged macrophytes. For example, the higher the concentration of antibiotics, the higher the proportion of Proteobacteria. These results suggest that high concentrations of oxytetracycline and sulfadiazine can disrupt homeostasis, induce effective Vallisneria natans defense mechanisms and alter biofilms in aquatic ecosystems.


Assuntos
Hydrocharitaceae , Microbiota , Oxitetraciclina , Antibacterianos/toxicidade , Antioxidantes/farmacologia , Biofilmes , Clorofila , Glutationa/farmacologia , Hydrocharitaceae/fisiologia , Oxitetraciclina/toxicidade , Folhas de Planta , Esgotos , Sulfadiazina/toxicidade , Superóxido Dismutase , Águas Residuárias
5.
Front Oncol ; 12: 916907, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35785154

RESUMO

Growing evidence has shown the oncogenic function of matrix metallopeptidase 7 (MMP7) in various tumors. However, no systemic pan-cancer analysis on the association between MMP7 and different cancers based on big clinical data is available. TIMER2, GEPIA2, UALCAN, cBioPortal, String, Metascape, and other web databases were searched in the present study. Generally, MMP7 expression is significantly upregulated in most The Cancer Genome Atlas (TCGA) cancer types compared to the paired normal controls, yet is downregulated in tumor tissues of invasive breast carcinoma (BRCA), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), and skin cutaneous melanoma (SKCM). MMP7 protein expression is notably higher in the primary tumor tissues of colon cancer, lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC) than in normal tissues and is significantly lower in the primary tumor tissues of breast cancer, clear cell renal carcinoma, and ovarian cancer. Furthermore, MMP7 expression is strongly associated with pathological stages, clinical outcomes, tumor mutational burden (TMB), and microsatellite instability (TSI). Gene amplification was detected in most TCGA cancer types. In addition, the missense mutation is the primary type of MMP7 genetic alteration in tumors. Significant positive correlations between MMP7 expression and cancer-associated fibroblasts (CAFs) have been demonstrated in most TCGA cancers. MMP7 expression was also found to be positively correlated with infiltration of dendritic cells and macrophages in some specific tumor types. Functional enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) methods revealed that RNA processing and DNA damage checkpoints might reveal the pathogenetic mechanisms of MMP7. This pan-cancer analysis provides a clear panorama for the tumorigenic roles of MMP7 across different cancer types. Moreover, MMP7 could be a potential drug therapeutic target in such cancers.

6.
Med Sci Monit ; 27: e931006, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34437515

RESUMO

BACKGROUND Respiratory function usually worsens in the elderly with aging. This study aimed to retrospectively investigate tracheal changes caused by "normal aging" through use of low-dose CT (LDCT) in non-smoking asymptomatic urban residents and the related factors influencing tracheal changes. MATERIAL AND METHODS A total of 733 Chinese subjects who underwent LDCT were recruited. The trachea shape, width, and calcification degree of the tracheal wall were measured and compared between males and females and among different age groups. The effects of age, sex, trachea morphology, BMI, BP, GLU, TC, TG, HDL, and LDL on the width and calcification of tracheal wall were analyzed by multiple linear regression. RESULTS Significant sex differences in trachea shape were found, as type II and type I were found mainly in the males and females, respectively. The values of anterior-posterior inner diameter (AP), left-right inner diameter (LR), width, and calcification score of tracheae in the males were higher than that in the females. In both males and females, trachea AP, wall width, and calcification scores increased with age, but this trend was not observed in tracheal LR. Age, sex, and trachea shape had significant effects on the width and calcification scores of tracheal walls, and trachea calcification was one of the factors influencing tracheal wall width. CONCLUSIONS Tracheal aging can be evaluated by measuring trachea shape, thickness, and the degree of calcification of the tracheal wall by LDCT, while sex and age should be taken into consideration comprehensively for judging normal trachea aging. In addition, obesity may aggravate trachea aging.


Assuntos
Envelhecimento , Traqueia/anatomia & histologia , Traqueia/fisiologia , Adulto , Fatores Etários , Idoso , China , Testes Diagnósticos de Rotina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Traqueia/diagnóstico por imagem
7.
J Inflamm Res ; 14: 85-95, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33488110

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. Oxidative stress plays a pivotal role in the pathogenesis of IBD. Selenium-containing amino acids reportedly have anti-oxidative and anti-inflammatory properties, but it remains unknown if selenium-containing amino acids can be used to treat IBD. This study aimed to investigate the effects of two selenium-containing amino acids - selenocysteine and selenocystine - on oxidative stress and chronic inflammation in a mouse model of dextran sulfate sodium (DSS)-induced IBD. METHODOLOGY: C57BL/6 mice were randomly assigned to the following six groups: control, DSS, DSS+selenocysteine, DSS+selenocystine, DSS+sodium selenite, and DSS+N-acetylcysteine (NAC). IBD was induced by 3% DSS. Pro-inflammatory cytokines [interleukin-1ß (IL-1ß), monocyte chemotactic protein 1 (MCP-1), IL-6, and tumor necrosis factor-α (TNF-α)] and markers for oxidative and anti-oxidative stress [malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured using immunohistochemical analysis. RESULTS: Selenocysteine and selenocystine significantly attenuated IBD-related symptoms, including preventing weight loss, decreasing disease activity index (DAI) scores, and increasing colon length. Selenocysteine and selenocystine significantly ameliorated the DSS-induced oxidative stress, as demonstrated by a reduction in ROS and MDA activity and an increase in SOD and GPx activity. IL-1, MCP-1, IL-6, and TNF-α levels were significantly increased in the IBD mice, while treatment with the selenium-containing amino acids significantly reduced the levels of these pro-inflammatory cytokines. In vivo safety analysis showed minimal side effects of the selenium-containing amino acids. CONCLUSION: We found that selenocysteine and selenocystine ameliorated DSS-induced IBD via reducing oxidative stress and intestinal inflammation, indicating that selenium-containing amino acids could be a novel therapeutic option for patients with IBD.

8.
World J Urol ; 39(4): 1211-1217, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32562046

RESUMO

INTRODUCTION: Yolk sac tumor (YST) is a rare malignant germ cell tumor, which usually affects young males. Because of the low incidence, few studies on YST have been published. In our study, we aim to investigate the clinical characteristics, survival and risk factors of male YST patients based on the Surveillance, Epidemiology, and End Results (SEER) program. METHODS: We identified 569 male YST patients from the SEER-18 database with additional treatment fields. Clinical characteristics, survival and prognostic factors were described in the study. Chi-square tests were applied to analyze categorical and continuous variables between different groups. Univariate and multivariate Cox proportional hazard model were performed to assess the relative impacts of risk factors on cancer-specific survival (CSS) in YST patients. Kaplan-Meier method and the log-rank test were used to analyze differences in survival that were significant. RESULTS: The major primary sites of YST were testis (74.69%), mediastinum (15.47%), retroperitoneum (2.64%) and central nervous system (1.24%). The 3-year and 5-year CSS was 70.0%, 56.5% vs. 97.2%, 96.0% for the mediastinal and testicular YST patients, respectively (p < 0.001). Primary site of mediastinum, distant SEER Summary stage were independent factors of poor prognosis (hazard ratio (HR) = 2.010 (1.094-3.695), p = 0.025; HR = 6.501 (2.294-18.424), p < 0.001, respectively). Receiving surgery was a good prognosis factor for all patients (HR = 0.495 (0.260-0.940), p = 0.032) and for the mediastinal group (p = 0.0019). Being treated with chemotherapy indicated poor outcome in all patients (HR = 3.624 (1.050-12.507), p = 0.042) and in the localized testicular YST patients (p = 0.0077). CONCLUSION: For the first time, our study revealed the primary site distribution of male YST, and summarized the clinical characteristics, survival and prognostic factors based on the SEER database, which provided important epidemiological evidence for clinical practice.


Assuntos
Tumor do Seio Endodérmico/diagnóstico , Tumor do Seio Endodérmico/mortalidade , Adulto , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Taxa de Sobrevida , Adulto Jovem
9.
Adv Sci (Weinh) ; 7(5): 1903089, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32154084

RESUMO

Single-atom catalysts (SACs) are efficient for maximizing electrocatalytic activity, but have unsatisfactory activity for the oxygen evolution reaction (OER). Herein, the NaCl template synthesis of individual nickel (Ni) SACs is reported, bonded to oxygen sites on graphene-like carbon (denoted as Ni-O-G SACs) with superior activity and stability for OER. A variety of characterizations unveil that the Ni-O-G SACs present 3D porous framework constructed by ultrathin graphene sheets, single Ni atoms, coordinating nickel atoms to oxygen. Consequently, the catalysts are active and robust for OER with extremely low overpotential of 224 mV at current density of 10 mA cm-2, 42 mV dec-1 Tafel slope, oxygen production turn over frequency of 1.44 S-1 at 300 mV, and long-term durability without significant degradation for 50 h at exceptionally high current of 115 mA cm-1, outperforming the state-of-the-art OER SACs. A theoretical simulation further reveals that the bonding between single nickel and oxygen sites results in the extraordinary boosting of OER performance of Ni-O-G SACs. Therefore, this work opens numerous opportunities for creating unconventional SACs via metal-oxygen bonding.

10.
Surg Endosc ; 33(12): 4192-4200, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31624942

RESUMO

BACKGROUND: Surgical management of gastric gastrointestinal stromal tumors (GISTs) has evolved towards minimal invasiveness. Laparoscopic wedge resection and laparoscopic and endoscopic cooperative surgery had been considered as standard surgical treatments for gastric GISTs > 2 cm. However, stomach deformation and the full-thickness gastric defect caused by these procedures may increase the risk of morbidity. To address these problems, we developed a novel technique, third space robotic and endoscopic cooperative surgery (TS-RECS), which could dissect the tumor entirely while preserving the intact mucosal layer. Here we performed a prospective evaluation of the feasibility and safety of TS-RECS. METHODS: Patients with gastric GISTs were recruited between April 2018 and April 2019. During the operation, the gastric GIST was located by endoscopic view firstly and the submucosal injection was performed. The tumor was then dissected through robotic surgery. Clinicopathological characteristics, operative data, adverse events, and follow-ups were prospectively collected and analyzed. RESULTS: A total of 20 patients with gastric GISTs received TS-RECS. The mean tumor size was 33.0 ± 7.3 mm. R0 resection was achieved in all patients with a median operation time of 115 min and a median blood loss of 20 ml. The integrity of mucosal layer was maintained in 95% (19/20) of the patients. All patients started oral diet on postoperative day 1 or 2, staying in the hospital for a median of 6 days after surgery. There were no major adverse events. Local or distant recurrences were not observed during a median follow-up period of 10 months. CONCLUSIONS: Our study suggests that TS-RECS appears to be a feasible and safe technique which could be an alternative method for resecting gastric GISTs > 2 cm. CLINICAL TRIALS: ClinicalTrials.gov NCT03804762.


Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Gastroscopia/métodos , Recidiva Local de Neoplasia/terapia , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Duração da Cirurgia , Estudos Prospectivos , Resultado do Tratamento
11.
J Vis Exp ; (150)2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31498319

RESUMO

The human appendix has been recently implicated to play important biological roles in the pathogenesis of various complex diseases, such as colorectal cancer, inflammatory bowel disease, and Parkinson's disease. To study the function of the appendix, a gut disease-associated murine appendectomy model has been established and its step-by-step protocol is described here. This report introduces a facile protocol for caecal patch removal in mice followed by the chemical induction of chronic colitis-associated colorectal cancer using a combination of dextran sulfate sodium (DSS) and azoxymethane (AOM). IgA specific cells and IgA concentration were significantly reduced upon removal of the caecal patch in male C57BL/6 mice compared to those in the sham group. Simultaneously administering 2% DSS and AOM resulted in nearly 80% mice survival in both sham and appendectomy groups without significant body weight loss. Histological results confirmed colonic inflammation and different degrees of adenocarcinoma. This model can be used for the study of the functional role of the appendix in maintaining gut microbiota homeostasis and pathogenesis of gut colitis and malignancies, as well as for the potential development of drug targeting therapies.


Assuntos
Adenocarcinoma/cirurgia , Apendicectomia , Colite/cirurgia , Neoplasias Colorretais/cirurgia , Modelos Animais de Doenças , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Animais , Azoximetano , Carcinógenos , Ceco/cirurgia , Doença Crônica , Colite/induzido quimicamente , Colite/complicações , Colite/patologia , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/patologia , Sulfato de Dextrana , Masculino , Camundongos Endogâmicos C57BL
12.
Nat Commun ; 10(1): 2359, 2019 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142744

RESUMO

Ambient sunlight-driven CO2 methanation cannot be realized due to the temperature being less than 80 °C upon irradiation with dispersed solar energy. In this work, a selective light absorber was used to construct a photothermal system to generate a high temperature (up to 288 °C) under weak solar irradiation (1 kW m-2), and this temperature is three times higher than that in traditional photothermal catalysis systems. Moreover, ultrathin amorphous Y2O3 nanosheets with confined single nickel atoms (SA Ni/Y2O3) were synthesized, and they exhibited superior CO2 methanation activity. As a result, 80% CO2 conversion efficiency and a CH4 production rate of 7.5 L m-2 h-1 were achieved through SA Ni/Y2O3 under solar irradiation (from 0.52 to 0.7 kW m-2) when assisted by a selective light absorber, demonstrating that this system can serve as a platform for directly harnessing dispersed solar energy to convert CO2 to valuable chemicals.

13.
Stat Med ; 38(14): 2605-2631, 2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-30887552

RESUMO

Thresholding variable plays a crucial role in subgroup identification for personalized medicine. Most existing partitioning methods split the sample based on one predictor variable. In this paper, we consider setting the splitting rule from a combination of multivariate predictors, such as the latent factors, principle components, and weighted sum of predictors. Such a subgrouping method may lead to more meaningful partitioning of the population than using a single variable. In addition, our method is based on a change point regression model and thus yields straight forward model-based prediction results. After choosing a particular thresholding variable form, we apply a two-stage multiple change point detection method to determine the subgroups and estimate the regression parameters. We show that our approach can produce two or more subgroups from the multiple change points and identify the true grouping with high probability. In addition, our estimation results enjoy oracle properties. We design a simulation study to compare performances of our proposed and existing methods and apply them to analyze data sets from a Scleroderma trial and a breast cancer study.


Assuntos
Modelos Estatísticos , Medicina de Precisão , Algoritmos , Neoplasias da Mama , Análise Fatorial , Feminino , Humanos , Projetos de Pesquisa
14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(3): 288-292, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30914087

RESUMO

OBJECTIVE: To explore the effects of bone marrow mesenchymal stem cells (BMSCs) in different concentrations on the balance of regulatory T cell/T-helper cell 17 (Treg/Th17). METHODS: BMSCs were isolated from SPF grade male Wistar rats with age of 3 weeks old and weight of 50 g. BMSCs were cultured and identified when they were expanded to the 4th generation. CD4+ T lymphocytes were isolated from SPF grade male Wistar rat with age of 6 weeks old and weight of 200 g and assayed for cell purity by flow cytometry. BMSCs were divided into 0.5-fold concentration group, basal concentration group, 2-fold concentration group and 4-fold concentration group by their concentrations of 1×105/well, 2×105/well, 4×105/well and 8×105/well, which were cultured with CD4+ T lymphocytes for 72 hours, respectively. Then the proportion of Treg cells and Th17 cells in each group was detected by flow cytometry, and cytokines were detected by cytometric bead array. RESULTS: The purities of BMSCs and CD4+ T lymphocytes were both higher than 95%. In the co-culture of BMSCs and CD4+ T lymphocytes, the proportions of Treg cells were statistically different among different concentration groups of BMSCs (F = 10.071, P = 0.001), in which BMSCs in 2-fold concentration group had the strongest ability to promote the Treg cells proliferation. The proportion of Treg cells in 2-fold concentration group was significantly higher than that in 0.5-fold concentration group, basal concentration group and 4-fold concentration group [(9.24±2.68)% vs. (3.87±0.38)%, (5.16±1.69)%, (3.86±0.36)%, all P < 0.01]. The level of interleukin-10 (IL-10) was lowest in 0.5-fold concentration group, and it was significantly lower than that in basal concentration group, 2-fold concentration group and 4-fold concentration group (ng/L: 39.80±14.48 vs. 148.43±64.49, 156.40±59.27, 126.92±42.95, all P < 0.05). Transforming growth factor-ß (TGF-ß) was the highest in basal concentration group, and it was significantly higher than that in 0.5-fold concentration group, 2-fold concentration group and 4-fold concentration group [ng/L: 3.17 (1.88, 5.74) vs. 0.71 (0.32, 1.38), 1.22 (0.47, 2.97), 0.52 (0.37, 1.23), all P < 0.05]. The proportions of Th17 cells were statistically different among the different concentration groups (F = 21.069, P = 0.000), with the highest proportion in basal concentration group which was significantly higher than that in 0.5-fold concentration group or 4-fold concentration group [(0.89±0.08)% vs. (0.64±0.15)%, (0.37±0.10)%, both P < 0.01], but no significant difference was found as compared with 2-fold concentration group [(0.83±0.06)%, P > 0.05]. However, the expressions of IL-17 and IL-6 were not different among the different concentration groups respectively (IL-17: χ2 = 0.550, P = 0.760; IL-6: χ2 = 0.010, P = 0.995). CONCLUSIONS: BMSCs in moderate concentrations [(2-4)×105/well] could promote proliferation both in Treg cells and Th17 cells, but no change could be found in higher concentrations of BMSCs (8×105/well). However, the changes in related cytokines were not synchronized with Treg/Th17 cells.


Assuntos
Células-Tronco Mesenquimais/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Animais , Citocinas/metabolismo , Masculino , Ratos , Ratos Wistar
15.
Waste Manag ; 85: 164-174, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30803569

RESUMO

Waste polyethylene terephthalate (PET) has been a core member in plastic polluters due to the great amount consumption in food packaging, soft-drink bottles, fibers and films. It is essential to recycle waste PET and alcoholysis is a significant way to accomplish chemical recycling. In this work, three kinds of dihydric alcohols, including neopentyl glycol (NPG), dipropylene glycol (DPG) and poly(propylene glycol) (PPG), were employed to decompose waste PET with different temperatures, catalysts, and PET. A series of alcoholysis products with different appearance were obtained. The bulk structure and thermal properties of alcoholysis products were investigated by FTIR, 1H NMR, MALDI-TOF, DSC and TG experiments. It is found that poly(propylene glycol) may react with waste PET to generate copolymer instead of oligomer products, dimers or trimers, etc. This product possesses excellent shelf stability and present transparent appearance, which may hold a great potential application in chemical industry. Moreover, the alcoholysis activity of DPG is the lowest comparing with NPG and EG in degradation of waste PET.


Assuntos
Ácidos Ftálicos , Polietilenotereftalatos , Etilenos , Reciclagem
16.
Clin Proteomics ; 15: 18, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719494

RESUMO

BACKGROUND: The development of clinically accessible biomarkers is critical for the early diagnosis of gastric cancer (GC) in patients. High-throughput proteomics techniques could not only effectively generate a serum peptide profile but also provide a new approach to identify potentially diagnostic and prognostic biomarkers for cancer patients. METHODS: In this study, we aim to identify potentially discriminating serum biomarkers for GC. In the discovery cohort, we screened potential biomarkers using magnetic-bead-based purification and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in 64 samples from 32 GC patients that were taken both pre- and post-operatively and 30 healthy volunteers that served as controls. In the validation cohort, the expression patterns and diagnostic values of serum FGA, AHSG and APOA-I were further confirmed by ELISA in 42 paired GC patients (pre- and post-operative samples from 16 patients with pathologic stage I/II and 26 with stage III/IV), 30 colorectal cancer patients, 30 hepatocellular carcinoma patients, and 28 healthy volunteers. RESULTS: ClinProTools software was used and annotated 107 peptides, 12 of which were differentially expressed among three groups (P < 0.0001, fold > 1.5). These 12 peptide peaks were further identified as FGA, AHSG, APOA-I, HBB, TXNRD1, GSPT2 and CAKP5. ELISA data suggested that the serum levels of FGA, AHSG and APOA-I in GC patients were significantly different compared with healthy controls and had favorable diagnostic values for GC patients. Moreover, we found that the serum levels of these three proteins were associated with TNM stages and could reflect tumor burden. CONCLUSION: Our findings suggested that FGA, AHSG and APOA-I might be potential serum biomarkers for GC diagnosis.

17.
Semin Cancer Biol ; 50: 124-131, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28965871

RESUMO

Digestive malignancies are the leading cause of mortality among all neoplasms, contributing to estimated 3 million deaths in 2012 worldwide. The mortality rate hassurpassed lung cancer and prostate cancer in recent years. The transcription factor Forkhead Box O1 (FOXO1) is a key member of Forkhead Box family, regulating diverse cellular functions during tumor initiation, progression and metastasis. In this review, we focus on recent studies investigating the antineoplastic role of FOXO1 in digestive malignancy. This review aims to serve as a guide for further research and implicate FOXO1 as a potent therapeutic target in digestive malignancy.


Assuntos
Carcinogênese/genética , Proteína Forkhead Box O1/genética , Neoplasias Gastrointestinais/genética , Neoplasias Hepáticas/genética , Progressão da Doença , Neoplasias Gastrointestinais/patologia , Humanos , Neoplasias Hepáticas/patologia , Metástase Neoplásica
18.
Tumour Biol ; 2016 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-27900564

RESUMO

This study examined the effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition. Different CoCl2 concentrations were used to treat A549 cells and establish a CoCl2-induced hypoxic model of A549 cells. MTT and clone formation assays were used to determine the effects of different concentrations of CoCl2 on the growth and proliferation of A549 cells treated by different doses of X-ray irradiation. The siRNA-expressing vector was transfected by liposomes and for silencing of TUSC3. Flow cytometry was used to measure cell cycle changes and apoptosis rate. Real-time quantitative polymerase chain reaction (qRT-PCR) assay was performed to detect the expression of TUSC3 mRNA. Western blotting was applied to detect the changes of TUSC3, LC3, and p62 proteins under different CoCl2 concentrations and after siRNA silencing of TUSC3. The TUSC3 levels in A549 cells increased under hypoxic conditions in a dose-dependent manner (P < 0.05). Hypoxia inhibited the growth and proliferation of A549 cells and promoted apoptosis (P < 0.05). With an increasing dose of X-ray irradiation, A549 cells showed significantly increased growth and proliferation and decreased apoptosis (P < 0.05). After siRNA-TUSC3 was transfected by liposome, the TUSC3 level was substantially inhibited (P < 0.05). Silencing TUSC3 inhibited A549 cell growth and proliferation after radiotherapy under hypoxic condition, promoted apoptosis, increased G0/G1 phase cells, and reduced S phase cells (all P < 0.05). Hypoxia and radiation along with different CoCl2 concentrations could induce cell autophagy, which increased with concentration and dose, while silencing the TUSC3 gene inhibited autophagy (all P < 0.05). RNAi silencing of TUSC3 inhibited growth and proliferation, while enhanced apoptosis and radiation sensitivity of hypoxic A549 lung adenocarcinoma cells.

19.
Burns ; 40(5): 974-80, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24290858

RESUMO

BACKGROUND: The purpose of this study was to explore the effectiveness and safety of three-dimensional (3D) digitalized planning for the sural neurovascular island flap in repair of soft tissue defects in the ankle and foot. METHODS: This study included 40 patients with soft tissue defects of the ankle and foot who underwent soft tissue reconstruction between October 2008 and June 2012. The patients were randomly assigned into two groups: 3D-reconstruction group (Group A, n=20) and control group (Group B, n=20). Three-dimensional, digitalized virtual planning was performed in the patients in Group A, who underwent computed topographic angiography. The survival rate, operation time, and surgical accuracy were compared between the two groups. RESULTS: All flaps in Group A survived and the recipient site primarily healed, but 4 flaps in Group B had marginal necrosis after the operation. During the 6-12 month follow-up period, all flaps in Group A had good skin quality. In Group B, hard scarring and mild contracture occurred in 4 cases, and the patients experienced pain when walking. The survival rate of the flap in Group A (100%) was significantly higher than in Group B (70%). The operation time in Group A was significantly less than in Group B. The surgical accuracy in Group A was significantly better than in Group B. CONCLUSION: The preoperative use of 3D digitalized virtual planning for the sural neurovascular island flap improves the surgical accuracy, decreases the operation time, and increases the survival rate of the flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic III.


Assuntos
Traumatismos do Tornozelo/cirurgia , Traumatismos do Pé/cirurgia , Modelos Anatômicos , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Nervo Sural , Retalhos Cirúrgicos/inervação , Interface Usuário-Computador , Adolescente , Adulto , Idoso , Traumatismos do Tornozelo/diagnóstico por imagem , Feminino , Traumatismos do Pé/diagnóstico por imagem , Sobrevivência de Enxerto , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Lesões dos Tecidos Moles/diagnóstico por imagem , Retalhos Cirúrgicos/irrigação sanguínea , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
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