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1.
Int Immunol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38955508

RESUMO

Regulatory T cells (Tregs) ameliorate inflammatory bowel diseases. However, their plasticity is not completely understood. In this study using a mouse colitis model, Tregs and T helper 17 (Th17)-like Tregs were detected and sorted using flow cytometry, followed by transcriptome sequencing, real-time RT-PCR, and flow cytometry to analyze the mRNA profiles of these cells. Treg plasticity was evaluated by in vitro differentiation assays. The immunosuppressive activities of Tregs and Th17-like Tregs were assessed in an adoptive transfer assay. We found Tregs-derived Th17-like Tregs in inflamed colonic lamina propria (LP). LP Th17-like Tregs expressed higher Th17-related cytokines and lower immunosuppressive cytokines compared with LP Tregs. Notably, Tregs expressed higher Yes-associated protein 1 (YAP1) but lower transcriptional coactivator with PDZ­binding motif (TAZ) than Th17-like Tregs. Verteporfin-mediated inhibition of YAP1 activity enhanced Th17-like Treg generation, whereas IBS008739-induced TAZ activation did not affect Th17-like Treg generation. Besides, verteporfin enhanced while IBS008739 suppressed the differentiation of Th17-like Tregs into Th17 cells. Furthermore, YAP1 activated STAT5 signaling in Tregs, whereas YAP1 and TAZ activated STAT3 and STAT5 signaling in Th17-like Tregs. Compared with Tregs, Th17-like Tregs were less efficacious in ameliorating colitis. Therefore, YAP1 suppressed Treg differentiation into Th17-like Tregs. Both YAP1 and TAZ inhibited the differentiation of Th17-like Tregs into Th17 cells. Therefore, YAP1 and TAZ probably maintain the immunosuppressive activities of Tregs and Th17-like Tregs in colitis.

2.
Am J Med Sci ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38944201

RESUMO

BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a pernicious tumor with high incidence and mortality rates. The incidence rate of NSCLC increases with age and poses a serious danger to human health. The aim of this study was to determine the mechanism by which (-)-epicatechin (EC) alleviates NSCLC. METHODS: Twenty-four pairs of NSCLC tissues and cancer-adjacent tissues were collected, and A549 and H460 radiotherapy-resistant strains were generated by repeatedly irradiating A549 and H460 cells with dose-gradient X-rays. Radiotherapy-resistant H460 cells were successfully injected subcutaneously into the left dorsal side of nude mice at a dose of 1 × 105 to establish an NSCLC animal model. The levels of interrelated genes and proteins were detected by RT‒qPCR and Western blotting, and cell proliferation and apoptosis were evaluated by CCK‒8 assay, Transwell assay, flow cytometry, and TUNEL staining. RESULTS: LOC107986454 was highly expressed in NSCLC patients, while miR-143-3p was expressed at low levels and was negatively correlated with LOC107986454. Functionally, EC promoted autophagy and apoptosis induced by radiotherapy, restrained cell proliferation and migration, and ultimately enhanced the radiosensitivity of NSCLC cells. A downstream mechanistic study showed that EC facilitated miR-143-3p expression by inhibiting LOC107986454 and then restraining the expression of EZH2, which ultimately facilitated autophagy and apoptosis in cancer cells, inhibited proliferation and migration, and enhanced the radiosensitivity of NSCLC cells. CONCLUSION: EC can enhance the radiosensitivity of NSCLC cells by regulating the LOC107986454/miR-143-3p/EZH2 axis.

3.
Cancer Control ; 31: 10732748241236333, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425007

RESUMO

BACKGROUND: Uncertainty surrounds the usefulness of inflammatory markers in hepatocellular carcinoma (HCC) patients for predicting postoperative pulmonary metastasis (PM). The purpose of this study was to assess the predictive value of inflammatory markers as well as to create a new nomogram model for predicting PM. METHODS: Cox regression was utilized to identify independent prognostic variables and to create a nomogram that predicted PM for comparison with a validation cohort and other prediction systems. We retrospectively analyzed a total of 1109 cases with HCC were included. RESULTS: The systemic inflammatory response index (SIRI) and aspartate aminotransferase-to-platelet ratio index (APRI) were independent risk factors for PM, with a concordance index of .78 (95% CI: .74-.81) for the nomogram. The areas under the curve of the nomograms for PM predicted at 1-, 3-, and 5-year were .82 (95% CI: .77-.87), .82 (95% CI: .78-.87) and .81 (95% CI: .75-.86), respectively, which were better than those of Barcelona Clinic Liver Cancer and China liver cancer stage. Decision curve analyses demonstrated a broader range of nomogram threshold probabilities. CONCLUSION: A nomogram based on SIRI and APRI can accurately predict postoperative PM in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Nomogramas , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Prognóstico , Neoplasias Pulmonares/cirurgia
4.
Immun Inflamm Dis ; 12(2): e1160, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38415949

RESUMO

INTRODUCTION: Regulatory T cells (Tregs) play an important role in inflammatory bowel diseases (IBDs) through modulating intestinal inflammation. However, the factors affecting Treg function and plasticity during IBD progression are not thoroughly disclosed. The current study aims to reveal new molecular mechanisms affecting Treg plasticity. METHODS: A mouse strain, in which tdTomato and enhanced green fluorescent protein were under the control of the Foxp3 promoter and Il17a promoter, was established and subjected to colitis induction with dextran sulfate sodium. The existence of Tregs and IL-17-expressing Tregs (i.e., Treg/T helper 17 [Th17] cells) were observed and sorted from the spleen, mesenteric lymph nodes, and lamina propria by flow cytometry, followed by measuring Sirtuin2 (Sirt2) expression using quantitative reverse transcription polymerase chain reaction and Immunoblotting. Lentivirus-induced Sirt2 silencing was applied to determine the impact of Sirt2 on Treg polarization to Treg/Th17 cells and even Th17 cells. The effect of Sirt2 on Stat3 was analyzed by flow cytometry and immunoblotting. RESULTS: Sirt2 was highly expressed in lamina propria Tregs and it moderately suppressed Foxp3 expression as well as the immunosuppressive function of Tregs. Surprisingly, lentivirus-mediated Sirt2 silencing promoted the generation of Treg/Th17 cells out of Tregs. Sirt2 silencing also enhanced the generation of Th17 cells out of Tregs under the Th17 induction condition. Furthermore, Sirt2 inhibited Th17 induction by suppressing the protein level of the signal transducer and activator of transcription 3. CONCLUSION: Sirt2 suppresses Treg function but also inhibits Treg polarization toward Treg/Th17 cells and Th17 cells. The ultimate effect of Sirt2 on colitis might depend on the balance among Tregs, Treg/Th17 cells, and Th17 cells.


Assuntos
Colite , Proteína Vermelha Fluorescente , Fator de Transcrição STAT3 , Animais , Camundongos , Fator de Transcrição STAT3/genética , Linfócitos T Reguladores , Células Th17 , Sirtuína 2/genética , Colite/induzido quimicamente , Colite/genética , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/genética
5.
DNA Cell Biol ; 42(8): 488-497, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37527208

RESUMO

Hepatocellular carcinoma (HCC) is one of the most fatal human malignancies worldwide. In this research, we aimed to identify long noncoding RNAs (lncRNAs) as biomarkers for HCC diagnosis and prognosis. lncRNA expression profiles were obtained from Gene Expression Omnibus and The Cancer Genome Atlas databases. The differentially expressed lncRNAs between HCC and adjacent tissues were analyzed with bioinformatic tools. Four lncRNAs with area under the curve of the receiver operating characteristic curve >0.9 were selected from both datasets. Univariate and Kaplan-Meier analyses were performed to obtain LINC01093, MYLK-AS1, and MCM3AP-AS1 as the optimal diagnostic and prognostic biomarkers. Finally, qPCR confirmed that LINC01093 and MYLK-AS1 were significantly differentially expressed in HCC and adjacent normal tissues. In general, we demonstrated that novel lncRNAs, LINC01093 and MYLK-AS1, could be used as potential diagnostic and prognostic biomarkers for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/genética , Acetiltransferases/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Ligação ao Cálcio/genética , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/metabolismo
6.
Mater Horiz ; 10(9): 3761-3772, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37404093

RESUMO

Interface engineering is a method of enhancing catalytic activity while maintaining a material's surface properties. Thus, we explored the interface effect mechanism via a hierarchical structure of MoP/CoP/Cu3P/CF. Remarkably, the heterostructure MoP/CoP/Cu3P/CF demonstrates an outstanding overpotential of 64.6 mV at 10 mA cm-2 with a Tafel slope of 68.2 mV dec-1 in 1 M KOH. DFT calculations indicate that the MoP/CoP interface in the catalyst exhibited the most favorable H* adsorption characteristics (-0.08 eV) compared to the pure phases of CoP (0.55 eV) and MoP (0.22 eV). This result can be attributed to the apparent modulation of electronic structures within the interface domains. Additionally, the CoCH/Cu(OH)2/CF‖MoP/CoP/Cu3P/CF electrolyzer demonstrates excellent overall water splitting performance, achieving 10 mA cm-2 in 1 M KOH solution with a modest voltage of only 1.53 V. This electronic structure adjustment via interface effects provides a new and efficient approach to prepare high-performance hydrogen production catalysts.

7.
Cancer Biol Ther ; 24(1): 2165896, 2023 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36861928

RESUMO

As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used in LUAD cases, and radiosensitivity is vital for LUAD therapy. This research sought to explore the genetic factors affecting radiosensitivity in LUAD and inner mechanisms. LINC00511, miR-497-5p, and SMAD3 expression in LUAD cells were detected via qRT-PCR and western blot. CCK-8 assays, colony formation, and flow cytometry assays were employed to explore the cell viability, apoptosis, and radiosensitivity in PC-9 and A549 cells. The targeting relationship between LINC00511, miR-497-5p, and SMAD3 was verified by dual luciferase reporter assay. Furthermore, xenograft experiments were performed for the in vivo verification. In conclusion, LINC00511 was overexpressed in LUAD cells, which downregulated downstream miR-497-5p expression and mediately led to SMAD3 activation. LINC00511 downregulation suppressed cell viability while enhanced apoptosis rate in LUAD cells. Also, LINC00511 and SMAD3 were overexpressed, while miR-497-5p was downregulated in LUAD cells exposed to 4Gy irradiation treatment. Moreover, LINC00511 inhibition could block SMAD3 expression and promoted the radiosensitivity both in vitro and in vivo. These findings uncover LINC00511 knockdown promoted miR-497-5p expression and subsequently led to lower SMAD3 level, which enhanced radiosensitivity in LUAD cells. LINC00511/miR-497-5p/SMAD3 axis could be of considerable potential to enhance radiosensitivity in LUAD.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Humanos , Tolerância a Radiação/genética , Sobrevivência Celular/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/radioterapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , MicroRNAs/genética , Proteína Smad3/genética
8.
Virchows Arch ; 482(4): 729-743, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36472661

RESUMO

Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (iTLPD-GI) is a rare neoplasm usually having an indolent clinical course and easily misdiagnosed as inflammatory bowel disease or other T-cell lymphomas. A subset of the disorders that progressed to overt peripheral T-cell lymphoma have been reported, and the etiology and pathogenesis are poorly understood. The current study retrospectively examined the pathological, molecular, and clinical features of 6 cases of iTLPD-GI. Hematoxylin and eosin staining, immunohistochemistry, in situ hybridization, T-cell receptor gene rearrangement, and next-generation sequencing (NGS) were performed with the diseased tissues. All the 6 patients were immunocompetent Chinese men, who presented with recurrent abdominal pain and diarrhea for 4 to 13 years. Histologically, the intestinal tissue was expanded by lymphoid infiltration, composed of small-to-medium-sized lymphocytes with gland intact. The neoplastic cells were CD4 - /CD8 + with expression of TIA1 and variable granzyme B in five cases, and the other one was CD4 + /CD8 - . Two of the 5 patients progressed to more aggressive T-cell lymphoma and died of disease with complications. NGS identified TET2 and DDX3X mutations in patient 1, and BIRC6 and REV3L mutations in patient 2. Literature review indicated that iTLPD-GI with CD4 - /CD8 + immunophenotype was more commonly reported in Chinese cases. Our limited data indicated CD4-/CD8 + iTLPD-GI have similar potential to progress to more aggressive T-cell lymphoma as that of CD4 + /CD8 - , and gradually increased expression of granzyme B and Ki-67 may be early signs of the disease progression. Gain of novel gene mutations may be indicators of the pathogenesis.


Assuntos
Neoplasias Gastrointestinais , Linfoma de Células T Periférico , Linfoma de Células T , Transtornos Linfoproliferativos , Masculino , Humanos , Granzimas , Estudos Retrospectivos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/patologia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Linfoma de Células T/patologia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patologia , Linfócitos T/patologia , Progressão da Doença , DNA Polimerase Dirigida por DNA , Proteínas de Ligação a DNA
9.
Biomed Res Int ; 2022: 9421738, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212722

RESUMO

Gastric insufflation for computed tomography (CT)-guided percutaneous gastrostomy is currently performed via a nasogastric tube or a Chiba needle. However, nasogastric tube placement requires patient pharynx and esophagus, and Chiba needle use is associated with an increased risk of organ damage and prolonged operation time. Herein, we introduce a new method of gastric insufflation via a central venous catheter and explore its safety and efficacy by retrospective analysis of the clinical data of patients who underwent percutaneous gastrostomy using this method in our hospital from April 2021 to March 2022. The extracted data included the following: success rate, operation time, gastric insufflation time, radiation dose, postoperative pain score, and complications. We also compared the preoperative levels of several nutritional indicators (body mass index, hemoglobin, albumin, creatinine, and blood urea nitrogen) with those obtained 1 month postoperatively. A total of 12 patients underwent percutaneous gastrostomy under CT guidance using central venous catheter gastric insufflation. The surgery and gastric insufflation success rates were 100% both. The average operation time, gastric insufflation time, and effective radiation dose were 24.08 ± 5.25 min, 5.08 ± 2.50 min, and 14.16 ± 3.63 mSv, respectively. Based on the World Health Organization scale for pain assessment, five patients reported no postoperative pain and seven patients had mild pain. There were no serious complications, such as stoma infection, peritonitis, gastrointestinal perforation and bleeding, or embedding syndrome. All evaluated nutritional indicators showed improvement at 1 month postoperatively, with statistically significant differences compared to the preoperative values (p < 0.05 for all). In conclusion, CT-guided percutaneous gastrostomy with central venous catheter gastric insufflation is a safe, effective, and feasible minimally invasive treatment.


Assuntos
Cateteres Venosos Centrais , Insuflação , Albuminas , Creatinina , Fluoroscopia/métodos , Gastrostomia/efeitos adversos , Gastrostomia/métodos , Humanos , Insuflação/efeitos adversos , Dor/etiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
10.
J Inflamm Res ; 15: 3587-3597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757458

RESUMO

Purpose: To retrospectively collect and analyze demographic information as well as symptoms, laboratory results, endoscopic and pathologic findings, and treatment of ulcerative colitis (UC) and Crohn's disease (CD) patients in Wuhan, China. Methods: Patients who were diagnosed as inflammatory bowel disease (IBD) and hospitalized from January 2012 to December 2017 were enrolled in this study. The clinical characteristics including symptoms, laboratory results, and treatment were reviewed and analyzed. Results: Totally 821 cases were screened, and finally 430 UC patients and 286 CD patients were selected and enrolled in this study. The most common symptom in UC patients was bloody stool (90.7%) followed by diarrhea (87.7%), mucus in stool (72.1%), and abdominal pain (66.3%), which were significantly different from those of CD patients (P < 0.01). In contrast, the most common symptom in CD patients was abdominal pain (80.0%) followed by diarrhea (58.4%), bloody stool (27.6%), and fever (18.2%). Erythrocyte sedimentation, C-reactive protein, and platelets were significantly increased, while hemoglobin was decreased, in the moderately or highly active IBD. The percentage of positive perinuclear anti-neutrophil cytoplasmic antibody was significantly higher in UC patients (31.1%) than that in CD patients (4.8%, P < 0.001), while the percentage of positive anti-intestinal goblet cell antibody was significantly higher in CD patients (23.1%) than that in UC patients (14.9%, P = 0.037). Conclusion: The findings of the current study may provide evidence-based information for Chinese gastroenterologists to treat IBD more effectively in the future.

11.
J Clin Pharm Ther ; 47(8): 1257-1263, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35397125

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Camrelizumab is a recently developed PD-1 inhibitor in China applied in treating different cancers including lung cancer. This study is designed to evaluate the efficacy, safety and prognostic factors for camrelizumab plus carboplatin and pemetrexed (CP) chemotherapy in treating patients with advanced lung adenocarcinoma. METHODS: Of 51 advanced lung adenocarcinoma patients with negative driver genes who received camrelizumab plus CP chemotherapy were recruited. These patients received four cycles of camrelizumab plus CP chemotherapy in a 21-day cycle. Then, camrelizumab, pemetrexed or camrelizumab plus pemetrexed was administered as maintenance therapy. RESULTS AND DISCUSSION: The rates of complete response, partial response, stable disease and progressive disease were 2.0%, 56.8%, 19.6% and 5.9%, respectively; while treatment response of 15.7% of patients was missing or not evaluable. The objective response and disease control rates were 58.8% and 78.4%, respectively. With a median follow-up period of 14.9 months (the follow-up duration ranged from 3.9 months to 24.3 months), 41 (83.4%) cases of disease progression and 22 (43.1%) cases of death were recorded. The median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI): 8.4-12.6 months) with a 1-year PFS rate of 36.3% and a 2-year PFS rate of 7.5%. In addition, the median overall survival (OS) was 18.7 months (95% CI: 16.4-21.0 months) with a 1-year OS rate of 79.1% and a 2-year OS rate of 30.4%. In consideration of safety, the most frequent adverse events were peripheral neuropathy (37.3%), neutropenia (37.3%), alopecia (35.3%), etc. and most of them were grade 1-2 and could be controlled. WHAT IS NEW AND CONCLUSION: Camrelizumab plus CP chemotherapy achieves favourable efficacy and tolerable adverse events in advanced lung adenocarcinoma patients.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/patologia , Pemetrexede/efeitos adversos , Prognóstico
12.
Cancer Manag Res ; 14: 377-386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35115834

RESUMO

PURPOSE: PD-1 inhibitors have been routinely used to treat advanced non-small cell lung cancer (NSCLC) and have significantly improved clinical outcomes. In this study, we aimed to explore the influence of pretreatment fibrinogen-albumin ratio (FAR) on treatment response and survival in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. PATIENTS AND METHODS: A total of 91 patients with advanced NSCLC were included in the study. All patients received at least two cycles of systemic first-line anti-PD-1 therapy plus platinum-based combination chemotherapy. Receiver operating characteristics analysis was performed to determine the optimal cutoff values of FAR. Univariate and multivariate analyses were used to identify independent prognostic factors, and the Kaplan-Meier method was used to estimate survival curves. RESULTS: Multivariate logistic regression analysis showed that N stage (N2-3) and high FAR (≥0.175, optimal cutoff value) were independent predictors for objective response rate (P = 0.0002, P = 0.0005, respectively). Multivariate Cox regression analysis of progression-free survival and overall survival showed that high FAR (≥0.145) was independent prognostic factors (P = 0.0061, P = 0.0024, respectively). Progression-free survival and overall survival were significantly shorter in the high FAR (≥0.145) group than those in the low FAR (<0.145) group (P = 0.0024, P = 0.0024, respectively). CONCLUSION: Pretreatment FAR was an independent predictor for treatment response and independent prognostic factors in advanced NSCLC patients treated with first-line anti-PD-1 therapy plus platinum-based combination chemotherapy.

13.
Cancer Biomark ; 31(3): 263-279, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33896835

RESUMO

BACKGROUND: Radiotherapy is one of main useful therapies in non-small cell lung cancer (NSCLC). Nevertheless, the underlying mechanism between NSCLC cell radiosensitivity and effective treatment remains unclear. OBJECTIVE: The aim is to explore the relationship between circular (circ) RNA and NSCLC cell radiosensitivity. METHODS: CircRNA plasmacytoma variant translocation 1 (PVT1) and microRNA (miR)-1208 expression in NSCLC cells were assessed using quantitative reverse transcriptase PCR (qRT-PCR). NSCLC cells were transfected with si-PVT1 or miR-1208 inhibitor and then exposed to irradiation. Cellular biology behaviors were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), colony formation, invasion and western blot. Additionally, binding between circPVT1 and miR-1208 was testified by dual-luciferase reporter and RIP assay. RESULTS: CircPVT1 was upregulated in NSCLC cells after irradiation treatment. Silencing circPVT1 induced inhibition of NSCLC cell growth and invasion, accompanied by cell apoptosis and γ-H2AX expression. Moreover, NSCLC cell proliferation and invasion was further inhibited by irradiation treatment in circPVT1-silenced cells, indicating a strong radiosensitivity of NSCLC cells. CircPVT1 functions as a competing endogenous RNA of miR-1208. Silencing miR-1208 reversed NSCLC cell sensitivity response to irradiation and activated PI3K/AKT/mTOR pathway in circPVT1-silenced cells. CONCLUSIONS: Silencing circPVT1 enhanced radiosensitivity of NSCLC cells by sponging miR-1208.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , MicroRNAs/metabolismo , RNA Circular/genética , RNA Longo não Codificante/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Transfecção , Regulação para Cima
14.
J Environ Pathol Toxicol Oncol ; 39(2): 137-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749123

RESUMO

Lung carcinogenesis is one of the main sources of cancer-related mortality globally and it is estimated that nearly 1 million people die from it every year. The 5-year survival rate of lung carcinogenesis is reported at just 15%. The aim of the current research was to investigate the immunomodulatory effect of eriocitrin against benzo(a)pyrene [B(a) P]-induced lung tumorigenesis in Swiss albino mice. The lung sarcoma was provoked through oral gavage of B(a)P (50 mg/kg body weight) two times/week for four weeks. CEA, lung weight, lipid peroxidation (LPO), body weight, immuno-globulin (IgG, IgA, and IgM), tumor incidence, serum marker enzymes (LDH, AHH, λ-GT, and 5'-NTs), hematological counts (leucocytes, lymphocytes, neutrophils, absolute numbers of lymphocytes and neutrophils), antioxidants (SOD and CAT), inflammatory modulators (IL-1ß, IL-6, and TNF-α), immune complexes (avidity index, phagocyte index, NBT reduction, and SIC) and histopathological changes were analyzed. Moreover, the status of apoptosis proteins (Bax, caspase-9, and caspase-3) and cell proliferative protein (cyclin D1 and cyclin A) expression was determined by Western blot and PCNA by immunohistochemical analysis. B(a)P-challenged cancer-bearing mice exhibited augmented levels of lipid peroxidation, tumor incidence, lung weight, CEA, serum marker enzymes, IgA, SIC, cell proliferative markers, and inflammatory cytokines with concurrent decrease in body weight, antioxidant levels, hematological counts, immunoglobulins, immune complexes, and apoptotic protein expression. The eriocitrin treatments caused significant reversion of all these marker to previous levels. Overall, the results propose the immunomodulatory prospective of eriocitrin against B(a) P-induced lung carcinogenesis on Swiss albino mice.


Assuntos
Flavanonas/farmacologia , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/prevenção & controle , Animais , Anticarcinógenos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Imunoglobulinas/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Fagócitos/efeitos dos fármacos
15.
BMC Gastroenterol ; 19(1): 145, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420025

RESUMO

BACKGROUND: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China. METHODS: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD. RESULTS: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission. CONCLUSIONS: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.


Assuntos
Doença de Crohn , Fatores Imunológicos/uso terapêutico , Administração dos Cuidados ao Paciente , Adulto , China/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/fisiopatologia , Doença de Crohn/terapia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Avaliação de Processos e Resultados em Cuidados de Saúde , Gravidade do Paciente , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Tempo para o Tratamento/estatística & dados numéricos
16.
Endocr Connect ; 8(5): 596-604, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30978696

RESUMO

OBJECTIVE: The protective effects of exercise against glucose dysmetabolism have been generally reported. However, the mechanism by which exercise improves glucose homeostasis remains poorly understood. The FGF21-adiponectin axis participates in the regulation of glucose metabolism. Elevated levels of FGF21 and decreased levels of adiponectin in obesity indicate FGF21-adiponectin axis dysfunction. Hence, we investigated whether exercise could improve the FGF21-adiponectin axis impairment and ameliorate disturbed glucose metabolism in diet-induced obese mice. METHODS: Eight-week-old C57BL/6J mice were randomly assigned to three groups: low-fat diet control group, high-fat diet group and high-fat diet plus exercise group. Glucose metabolic parameters, the ability of FGF21 to induce adiponectin, FGF21 receptors and co-receptor levels and adipose tissue inflammation were evaluated after 12 weeks of intervention. RESULTS: Exercise training led to reduced levels of fasting blood glucose and insulin, improved glucose tolerance and better insulin sensitivity in high-fat diet-induced obese mice. Although serum FGF21 levels were not significantly changed, both total and high-molecular-weight adiponectin concentrations were markedly enhanced by exercise. Importantly, exercise protected against high-fat diet-induced impaired ability of FGF21 to stimulate adiponectin secretion. FGF21 co-receptor, ß-klotho, as well as receptors, FGFR1 and FGFR2, were upregulated by exercise. We also found that exercise inhibited adipose tissue inflammation, which may contribute to the improvement in the FGF21-adiponectin axis impairment. CONCLUSIONS: Our data indicate exercise protects against high-fat diet-induced FGF21-adiponectin axis impairment, and may thereby exert beneficial effects on glucose metabolism.

17.
Eur J Mass Spectrom (Chichester) ; 25(5): 412-418, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31006258

RESUMO

Histamine is an organic nitrogenous compound that acts as a neurotransmitter in the uterus, spinal cord, and brain and is involved in local immune responses. In this study, we developed a fast and simple derivatization method based on reductive amination that can be used to quantify histamine by hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry. Histamine isotope analogs were synthesized via reductive amination. Histamine was modified with H2-formaldehyde to form N-dimethylated histamine to act as a standard or with D2-formaldehyde to form N-dimethylated histamine-d4 to act as an internal standard. Using this method, we achieved a limit of detection of 3.6 ng/mL, a limit of quantification of 7.9 ng/mL, and a linear calibration curve with a coefficient of determination (R2) of 0.9987. Furthermore, the intra-day relative standard deviations ranged from 0.9% to 3.7% and the inter-day relative standard deviations ranged from 2.0% to 17.6%. After derivatization, N-dimethylated histamine showed 382.5% signal enhancement compared to unmodified histamine in mass spectrometry detection. To demonstrate the applicability of this method for biological samples, we utilized standard addition method to quantify histamine in fetal bovine serum and achieved a recovery of 86.7%.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Histamina/química , Espectrometria de Massas em Tandem/métodos , Aminação , Animais , Bovinos , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Soroalbumina Bovina/química
18.
J Food Prot ; 82(4): 696-702, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30917042

RESUMO

HIGHLIGHTS: A reductive amination-assisted method was used to synthesize standards and internal standards of ractopamine and salbutamol. Standard and internal standard analogs were fabricated by isotopic formaldehydes and sodium cyanoborohydride. A quantitative method of modified ractopamine and salbutamol was successfully validated. The reductive amination-assisted method enhances the signal for MS detection.


Assuntos
Agonistas Adrenérgicos beta/análise , Albuterol , Aminação , Fenetilaminas , Espectrometria de Massas em Tandem
19.
Am J Gastroenterol ; 114(3): 490-499, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30741735

RESUMO

OBJECTIVES: Differentiating Crohn's disease (CD) from intestinal tuberculosis (ITB) remains a diagnostic challenge. Misdiagnosis carries potential grave implications. We aimed to develop and validate a novel diagnostic nomogram for differentiating them. METHODS: In total, 310 eligible patients were recruited from 6 tertiary inflammatory bowel disease centers. Among them, 212 consecutive patients (143 CD and 69 ITB) were used in the derivation cohort for the establishment of diagnostic equation and nomogram; 7 investigative modalities including clinical manifestations, laboratory results, endoscopic findings, computed tomography enterography features, and histology results were used to derive the diagnostic model and nomogram. Ninety-eight consecutive patients (76 CD and 22 ITB) were included for validation of the diagnostic model. RESULTS: Eight out of total 79 parameters were identified as valuable parameters used for establishing diagnostic equations. Two regression models were built based on 7 differential variables: age, transverse ulcer, rectum involvement, skipped involvement of the small bowel, target sign, comb sign, and interferon-gamma release assays (for model 1) or purified protein derivative (for model 2), respectively. Accordingly, 2 nomograms of the above 2 models were developed for clinical practical use, respectively. Further validation test verified the efficacy of the nomogram 1 with 90.9% specificity, 86.8% sensitivity, 97.1% PPV, 66.7% negative predictive value (NPV), and 87.8% accuracy for identifying CD, and the efficacy of the nomogram 2 with 100% specificity, 84.2% sensitivity, 100% positive predictive value, 64.7% NPV, and 87.8% accuracy for diagnosing CD. CONCLUSIONS: The derivation and validation cohorts identified and validated 2 highly accurate and practical diagnostic nomograms for differentiating CD from ITB. These diagnostic nomograms can be conveniently used to identify some difficult CD or ITB cases, allowing for decision-making in a clinical setting.


Assuntos
Doença de Crohn/diagnóstico , Enteropatias/diagnóstico , Nomogramas , Tuberculose Gastrointestinal/diagnóstico , Adolescente , Adulto , Biópsia , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
J Chromatogr A ; 1565: 96-104, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-29983170

RESUMO

Maleic acid (MA), an industrial raw material, was found to be illegally added to edible starch-based food products in Taiwan in 2013, a practice unheard of in most of the world. MA has been associated with renal dysfunction in many experimental animal studies. In this study, we developed chemical probes to investigate protein-protein interactions between MA and renal proteins. In the fabrication of the MA probes, we used silicon dioxide (SiO2) modified with a silanized linker (3-aminopropyl triethoxyslane, APTES) to generate MA with APTES-SiO2 particles. The probes were then incubated with the cell lysates of normal human kidney cell lines (HK-2) and subjected to MS/MS for identifying several MA-related proteins, including nucleophosmin, neutral alpha-glucosidase AB, translocon-associated protein subunit alpha, elongation factor 1-gamma, 60S acidic ribosomal protein P0-like, and heat shock protein (HSP 90-alpha and beta). Based on our findings, we believed that the probe can potentially be used to identify and detect the target proteins and help characterize a network of MA protein-protein interactions.


Assuntos
Túbulos Renais/lesões , Túbulos Renais/metabolismo , Maleatos/toxicidade , Sondas Moleculares/química , Proteômica/métodos , Animais , Linhagem Celular , Cromatografia Líquida , Humanos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Sondas Moleculares/síntese química , Proteínas/metabolismo , Dióxido de Silício/química , Espectrofotometria Infravermelho , Espectrometria de Massas em Tandem
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