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1.
Front Nutr ; 11: 1423651, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39183989

RESUMO

Background and purpose: This study explores the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and mortality among Parkinson's disease (PD) patients, providing evidence for the potential benefits of vitamin D (VD) supplementation. Methods: PD patients were collected from the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2020. These patients were categorized based on their serum 25(OH)D levels: deficiency, insufficiency, and sufficiency. We compared demographic information and analyzed mortality data from the National Death Index. A restricted cubic spline model assessed the nonlinear association between 25(OH)D levels and mortality, complemented by multivariable Cox regression analysis. Consistency of results was checked through subgroup analysis. Results: The study included 364 PD patients: 87 (23.9%) with VD deficiency, 121 (33.2%) with insufficiency, and 156 (42.9%) with sufficiency. Demographically, 46.4% were male, and 56% were over 65 years. The deficiency group predominantly consisted of Mexican Americans (53.1%), had lower income levels, a higher unmarried rate, and increased liver disease incidence. The analysis showed a U-shaped curve between 25(OH)D levels and mortality risk, with the lowest risk at 78.68 nmol/L (p-non-linear = 0.007, p-overall = 0.008). Kaplan-Meier analysis found the highest survival rates in patients with 25(OH)D levels between 75-100 nmol/L (p = 0.039). Compared to this group, patients with levels below 50 nmol/L had a 3.52-fold increased mortality risk (95% CI = 1.58-7.86, p = 0.002), and those above 100 nmol/L had a 2.92-fold increase (95% CI = 1.06-8.05, p = 0.038). Age-specific subgroup analysis (p = 0.009) revealed that both very low (<50 nmol/L) and high (>100 nmol/L) levels increased mortality risk in patients under 65, while levels below 75 nmol/L raised mortality risk in older patients. Conclusion: Serum 25(OH)D levels are nonlinearly linked to mortality in PD patients, with optimal survival rates occurring at 75-100 nmol/L. Deviations from this range increase the risk of death.

2.
J Colloid Interface Sci ; 677(Pt A): 941-952, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39128288

RESUMO

Prodrug nanoassemblies combine the advantages of prodrug strategies and nanotechnology have been widely utilized for delivering antitumor drugs. These prodrugs typically comprise active drug modules, response modules, and modification modules. Among them, the modification modules play a critical factor in improving the self-assembly ability of the parent drug. However, the impact of the specific structure of the modification modules on prodrug self-assembly remains elusive. In this study, two gemcitabine (GEM) prodrugs are developed using 2-octyl-1-dodecanol (OD) as flexible modification modules and cholesterol (CLS) as rigid modification modules. Interestingly, the differences in the chemical structure of modification modules significantly affect the assembly performance, drug release, cytotoxicity, tumor accumulation, and antitumor efficacy of prodrug nanoassemblies. It is noteworthy that the prodrug nanoassemblies constructed with flexible modifying chains (OD) exhibit improved stability, faster drug release, and enhanced antitumor effects. Our findings elucidate the significant impact of modification modules on the construction of prodrug nanoassemblies.

3.
Clin Neurol Neurosurg ; 243: 108361, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851120

RESUMO

OBJECTIVE: We conducted a cross-sectional study to investigate the impact of hyperhomocysteinemia (HHcy) on the prevalence of CASP among middle-aged individuals, aiming to provide insights for CASP prevention. METHODS: 1105 subjects were categorized into HHcy group or normal tHcy group based on their plasma total homocysteine (tHcy). All participants underwent carotid artery ultrasonography to assess the presence of unilateral and bilateral CASP. Comparative analyses of demographic and clinical data were conducted between the two groups. Logistic regression and prespecified subgroup analyses were performed to determine whether HHcy independently contributed to bilateral CASP. RESULTS: 132 individuals exhibited bilateral CASP. The prevalence of bilateral CASP was significantly higher in the HHcy group compared to the normal tHcy group (21.55 % vs. 10.82 %, p = 0.003). Univariate logistic analysis showed a significant association between HHcy and the prevalence of bilateral CASP (OR = 2.056, 95 %CI 1.089-3.881, p = 0.026). In all four models of multivariate logistic analysis, HHcy consistently emerged as an independent risk factor for bilateral CASP, with odd ratios of 1.958, 2.047, 2.023, and 2.186. This association remained significant across all five subgroups stratified by age, sex, hypertension, diabetes, and BMI. CONCLUSION: Our studies demonstrated HHcy was an independent risk factor for the prevalence of bilateral CASP in the middle-aged population. Theses results emphasized the importance of addressing HHcy in preventive strategies aimed at mitigating the burden of CASP among middle-aged individuals.


Assuntos
Doenças das Artérias Carótidas , Hiper-Homocisteinemia , Placa Aterosclerótica , Humanos , Hiper-Homocisteinemia/epidemiologia , Hiper-Homocisteinemia/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Prevalência , Estudos Transversais , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Fatores de Risco , Idoso , Homocisteína/sangue , Adulto
4.
J Ultrasound Med ; 43(9): 1611-1625, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38808580

RESUMO

OBJECTIVE: This study seeks to construct a machine learning model that merges clinical characteristics with ultrasound radiomic analysis-encompassing both the intratumoral and peritumoral-to predict the status of axillary lymph nodes in patients with early-stage breast cancer. METHODS: The study employed retrospective methods, collecting clinical information, ultrasound data, and postoperative pathological results from 321 breast cancer patients (including 224 in the training group and 97 in the validation group). Through correlation analysis, univariate analysis, and Lasso regression analysis, independent risk factors related to axillary lymph node metastasis in breast cancer were identified from conventional ultrasound and immunohistochemical indicators, and a clinical feature model was constructed. Additionally, features were extracted from ultrasound images of the intratumoral and its 1-5 mm peritumoral to establish a radiomics feature formula. Furthermore, by combining clinical features and ultrasound radiomics features, six machine learning models (Logistic Regression, Decision Tree, Support Vector Machine, Extreme Gradient Boosting, Random Forest, and K-Nearest Neighbors) were compared for diagnostic efficacy, and constructing a joint prediction model based on the optimal ML algorithm. The use of Shapley Additive Explanations (SHAP) enhanced the visualization and interpretability of the model during the diagnostic process. RESULTS: Among the 321 breast cancer patients, 121 had axillary lymph node metastasis, and 200 did not. The clinical feature model had an AUC of 0.779 and 0.777 in the training and validation groups, respectively. Radiomics model analysis showed that the model including the Intratumor +3 mm peritumor area had the best diagnostic performance, with AUCs of 0.847 and 0.844 in the training and validation groups, respectively. The joint prediction model based on the XGBoost algorithm reached AUCs of 0.917 and 0.905 in the training and validation groups, respectively. SHAP analysis indicated that the Rad Score had the highest weight in the prediction model, playing a significant role in predicting axillary lymph node metastasis in breast cancer. CONCLUSION: The predictive model, which integrates clinical features and radiomic characteristics using the XGBoost algorithm, demonstrates significant diagnostic value for axillary lymph node metastasis in breast cancer. This model can provide significant references for preoperative surgical strategy selection and prognosis evaluation for breast cancer patients, helping to reduce postoperative complications and improve long-term survival rates. Additionally, the utilization of SHAP enhancing the global and local interpretability of the model.


Assuntos
Axila , Neoplasias da Mama , Linfonodos , Metástase Linfática , Aprendizado de Máquina , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Estudos Retrospectivos , Adulto , Valor Preditivo dos Testes , Idoso , Ultrassonografia Mamária/métodos , Radiômica
5.
J Gastrointest Surg ; 28(4): 425-433, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583892

RESUMO

PURPOSE: This study aimed to analyze the clinical effect of simultaneous resection of liver metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on synchronous colorectal cancer liver metastasis. METHODS: A total of 144 patients with synchronous colorectal cancer liver metastasis who were admitted to our hospital between January 2018 and January 2019 were randomly assigned into a control group and an intervention group. The patients in the control group received simultaneous resection of liver metastases. The patients in the intervention group obtained simultaneous resection of liver metastases combined with HIPEC. The recent total effective rate of the 2 groups was compared, and the disease control rate of the 2 groups was calculated at 3 months after treatment. The patients were followed up for 3 years. The survival time of the 2 groups was observed and compared. Fasting venous blood was collected from patients in the 2 groups, and the carcinoembryonic antigen (CEA) level was compared. The level of quality of life scale (Short Form 36-item Health Survey) and the occurrence of adverse reactions were compared between the 2 groups. RESULTS: The R0 complete resection rate in the intervention group was significantly higher than that in the control group (P < .05). The recent total effective rate in the intervention group (87.50%) was significantly higher than that in the control group (59.72%) (P < .05). The negative change of CEA in the intervention group was 72.22%, which was prominently higher than that in the control group of 43.06% (χ2 = 12.542, P < .001). After a 36-month follow-up, the overall survival rate of the observation group was significantly higher than that of the control group (hazard ratio, 2.54; 95% CI, 1.05-5.48; P < .001). The patients in the intervention group had significantly higher life quality scores of health status, social function, emotional function, physical function, and mental health than in the control group (P < .05). There was no significant difference in the incidence of complications between the 2 groups (P > .05). Age > 60 years, preoperative comorbidities, moderate and high differentiation of tumors, intraoperative blood loss > 150 mL, and less experienced surgeons were risk factors affecting the occurrence of complications after treatment and were closely correlated with the prognosis and survival of patients (P < .05). Patients with age ≤ 60 years, no preoperative comorbidities, low tumor differentiation, intraoperative blood loss ≤ 150 mL, more experienced surgeons, and complete R0 resection had a longer survival time. Age > 60 years, preoperative comorbidities, moderate and high differentiation of tumors, intraoperative blood loss > 150 mL, and less experienced surgeons were independent risk factors affecting the prognosis of patients with colorectal cancer liver metastases (P < .05), whereas R0 surgery was an independent protective factor for the prognosis (P < .05). CONCLUSION: In the treatment of synchronous colorectal cancer liver metastases, simultaneous resection of liver metastases in conjunction with HIPEC demonstrated superior efficacy. This approach may potentially extend patient survival and enhance quality of life and deserve to be extensively used in clinical practice.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Quimioterapia Intraperitoneal Hipertérmica , Antígeno Carcinoembrionário , Perda Sanguínea Cirúrgica , Qualidade de Vida , Neoplasias Colorretais/cirurgia , Hepatectomia , Estudos Retrospectivos , Terapia Combinada , Neoplasias Hepáticas/cirurgia , Taxa de Sobrevida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
6.
J Diabetes ; 16(3): e13508, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38036859

RESUMO

BACKGROUND: Diabetic kidney disease (DKD) is the most frequent complication in patients with type 2 diabetes mellitus (T2DM). It causes a chronic and progressive decline in kidney function, and ultimately patients require renal replacement therapy. To date, an increasing number of clinical studies have been conducted to explore the potential and novel biomarkers, which can advance the diagnosis, estimate the prognosis, and optimize the therapeutic strategies at the early stage of DKD. In the current study, we sought to investigate the association of plasma myoglobin with DKD. METHODS: A total of 355 T2DM patients with DKD and 710 T2DM patients without DKD were enrolled in this study. Laboratory parameters including blood cell count, hemoglobin A1c, biochemical parameters, and plasma myoglobin were recorded. Patients were classified on admission according to the tertile of myoglobin and clinical parameters were compared between the groups. Pearson correlation analysis, linear regression, logistic regression, receiver operating characteristics (ROC) analysis, and spline regression were performed. RESULTS: Plasma myoglobin significantly increased in patients with DKD and was associated with renal function and inflammatory parameters. Plasma myoglobin was an independent risk factor for the development of DKD. The area under ROC curve of myoglobin was 0.831. Spline regression showed that there was a significant linear association between DKD incidence and a high level of plasma myoglobin when it exceeded 36.4 mg/mL. CONCLUSIONS: This study shows that elevated plasma myoglobin level is closely associated with the development of kidney injury in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Mioglobina , Taxa de Filtração Glomerular , Rim
7.
Nano Lett ; 24(1): 394-401, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38147432

RESUMO

The prodrug-based nanoassemblies offer an alternative to settle the deficiencies of traditional chemotherapy drugs. In this nanosystem, prodrugs typically comprise drug modules, modification modules, and response modules. The response modules are crucial for facilitating the accurate conversion of prodrugs at specific sites. In this work, we opted for differentiated disulfide bonds as response modules to construct docetaxel (DTX) prodrug nanoassemblies. Interestingly, a subtle change in response modules leads to a "U-shaped" conversion rate of DTX-prodrug nanoassemblies. Prodrug nanoassemblies with the least carbon numbers between the disulfide bond and ester bond (PDONα) offered the fastest conversion rate, resulting in powerful treatment outcomes with some unavoidable toxic effects. PDONß, with more carbon numbers, possessed a slow conversion rate and poor antitumor efficacy but good tolerance. With most carbon numbers in PDONγ, it demonstrated a moderate conversion rate and antitumor effect but induced a risk of lethality. Our study explored the function of response modules and highlighted their importance in prodrug development.


Assuntos
Antineoplásicos , Nanopartículas , Pró-Fármacos , Docetaxel , Pró-Fármacos/química , Linhagem Celular Tumoral , Dissulfetos/química , Carbono , Antineoplásicos/farmacologia , Nanopartículas/química
8.
J Clin Ultrasound ; 52(3): 274-283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38105371

RESUMO

BACKGROUND: Explore the feasibility of using the multimodal ultrasound (US) radiomics technology to diagnose American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) 4-5 thyroid nodules. METHOD: This study prospectively collected the clinical characteristics, conventional, and US elastography images of 100 patients diagnosed with ACR TI-RADS 4-5 nodules from May 2022 to 2023. Independent risk factors for malignant thyroid nodules were extracted and screened using methods such as the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model, and a multimodal US radiomics combined diagnostic model was established. Using a multifactorial LR analysis and a Rad-score rating, the predictive performance was validated and evaluated, and the final threshold range was determined to assess the clinical net benefit of the model. RESULTS: In the training set, the US radiomics combined predictive model area under curve (AUC = 0.928) had higher diagnostic performance compared with clinical characteristics (AUC = 0.779), conventional US (AUC = 0.794), and US elastography model (AUC = 0.852). In the validation set, the multimodal US radiomics combined diagnostic model (AUC = 0.829) also had higher diagnostic performance compared with clinical characteristics (AUC = 0.799), conventional US (AUC = 0.802), and US elastography model (AUC = 0.718). CONCLUSION: Multi-modal US radiomics technology can effectively diagnose thyroid nodules of ACR TI-RADS 4-5, and the combination of radiomics signature and conventional US features can further improve the diagnostic performance.


Assuntos
Técnicas de Imagem por Elasticidade , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Radiômica , Estudos Retrospectivos , Ultrassonografia/métodos , Tecnologia
9.
J Control Release ; 360: 784-795, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37451544

RESUMO

The clinical application of cabazitaxel (CTX) is restricted by severe dose-related toxicity, failing to considering therapeutic efficacy and safety together. Self-assembled prodrugs promote new drug delivery paradigms as they can self-deliver and self-formulate. However, the current studies mainly focused on the use of straight chains to construct self-assembled prodrugs, and the role of branched chains in prodrug nanoassemblies remains to be clarified. In this study, we systematically explored the structure-function relationship of prodrug nanoassemblies using four CTX prodrugs that contained branched chain aliphatic alcohols (BAs) with different alkyl lengths. Overall, CTX-SS-BA20 NPs with the proper alkyl length exhibited significant improvements in both antitumor efficacy and biosafety. Furthermore, compared with straight chain (SC) modified prodrug nanoassemblies (CTX-SS-SC20 NPs), CTX-SS-BA20 NPs still hold great therapeutic promise due to its good biosafety. These findings illustrated the significance of BAs as modified chains in designing prodrug nanoassemblies for narrowing the efficacy-to-safety gap of cancer therapy.


Assuntos
Nanopartículas , Pró-Fármacos , Sistemas de Liberação de Medicamentos , Taxoides , Linhagem Celular Tumoral
10.
Front Oncol ; 13: 1060702, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37251934

RESUMO

Artificial intelligence (AI), particularly deep learning (DL) algorithms, has demonstrated remarkable progress in image-recognition tasks, enabling the automatic quantitative assessment of complex medical images with increased accuracy and efficiency. AI is widely used and is becoming increasingly popular in the field of ultrasound. The rising incidence of thyroid cancer and the workload of physicians have driven the need to utilize AI to efficiently process thyroid ultrasound images. Therefore, leveraging AI in thyroid cancer ultrasound screening and diagnosis cannot only help radiologists achieve more accurate and efficient imaging diagnosis but also reduce their workload. In this paper, we aim to present a comprehensive overview of the technical knowledge of AI with a focus on traditional machine learning (ML) algorithms and DL algorithms. We will also discuss their clinical applications in the ultrasound imaging of thyroid diseases, particularly in differentiating between benign and malignant nodules and predicting cervical lymph node metastasis in thyroid cancer. Finally, we will conclude that AI technology holds great promise for improving the accuracy of thyroid disease ultrasound diagnosis and discuss the potential prospects of AI in this field.

11.
Nano Lett ; 23(8): 3549-3557, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37053460

RESUMO

Prodrug-based nanoassemblies have been developed to solve the bottlenecks of chemotherapeutic drugs. The fabricated prodrugs usually consist of active drug modules, response modules, and modification modules. Among three modules, the response modules play a vital role in controlling the intelligent drug release at tumor sites. Herein, various locations of disulfide bond linkages were selected as response modules to construct three Docetaxel (DTX) prodrugs. Interestingly, the small structural difference caused by the length of response modules endowed corresponding prodrug nanoassemblies with unique characteristic. α-DTX-OD nanoparticles (NPs) possessed the advantages of high redox-responsiveness due to their shortest linkages. However, they were too sensitive to retain the intact structure in the blood circulation, leading to severe systematic toxicity. ß-DTX-OD NPs significantly improved the pharmacokinetics of DTX but may induce damage to the liver. In comparison, γ-DTX-OD NPs with the longest linkages greatly ameliorated the delivery efficiency of DTX as well as improved DTX's tolerance dose.


Assuntos
Antineoplásicos , Nanopartículas , Pró-Fármacos , Docetaxel , Pró-Fármacos/química , Nanopartículas/química , Liberação Controlada de Fármacos , Antineoplásicos/química , Linhagem Celular Tumoral , Portadores de Fármacos/química
13.
Front Oncol ; 12: 990603, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439514

RESUMO

Objective: This study compared the diagnostic value of various diagnostic methods for lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC) through network meta-analysis. Methods: In this experiment, databases such as CNKI, Wanfang, PubMed, and Web of Science were retrieved according to the Cochrane database, Prisma, and NMAP command manual. A meta-analysis was performed using STATA 15.0, and the value of the surface under the cumulative ranking curve (SUCRA) was used to determine the most effective diagnostic method. Quality assessments were performed using the Cochrane Collaboration's risk of bias tool, and publication bias was assessed using Deeks' funnel plot. Results: A total of 38 articles with a total of 6285 patients were included. A total of 12 diagnostic methods were used to study patients with LNM of PTC. The results showed that 12 studies were direct comparisons and 8 studies were indirect comparisons. According to the comprehensive analysis of the area of SUCRA, US+CT(86.8) had the highest sensitivity, FNAC had the highest specificity (92.4) and true positive predictive value (89.4), and FNAC+FNA-Tg had higher negative predictive value (99.4) and accuracy (86.8). In the non-invasive method, US+CT had the highest sensitivity, and the sensitivity (SEN) was [OR=0.59, 95% confidence interval (CI): (0.30, 0.89]. Among the invasive methods, the combined application of FNAC+FNA-Tg had higher diagnostic performance. The sensitivity was [OR=0.62, 95% CI: (0.26, 0.98)], the specificity (SPE) was [OR=1.12, 95% CI: (0.59, 1.64)], the positive predictive value was [OR=0.98, 95% CI: (0.59, 1.37)], the negative predictive value was [OR=0.64, 95% CI (0.38, 0.90)], and the accuracy was [OR=0.71, 95% CI: (0.31, 1.12)]. Conclusion: In the non-invasive method, the combined application of US+CT had good diagnostic performance, and in the invasive method, the combined application of FNAC+FNA-Tg had high diagnostic performance, and the above two methods were recommended.

14.
Front Oncol ; 12: 944859, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249056

RESUMO

Objective: The aim of this study was to evaluate the accuracy of deep learning using the convolutional neural network VGGNet model in distinguishing benign and malignant thyroid nodules based on ultrasound images. Methods: Relevant studies were selected from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases, which used the deep learning-related convolutional neural network VGGNet model to classify benign and malignant thyroid nodules based on ultrasound images. Cytology and pathology were used as gold standards. Furthermore, reported eligibility and risk bias were assessed using the QUADAS-2 tool, and the diagnostic accuracy of deep learning VGGNet was analyzed with pooled sensitivity, pooled specificity, diagnostic odds ratio, and the area under the curve. Results: A total of 11 studies were included in this meta-analysis. The overall estimates of sensitivity and specificity were 0.87 [95% CI (0.83, 0.91)] and 0.85 [95% CI (0.79, 0.90)], respectively. The diagnostic odds ratio was 38.79 [95% CI (22.49, 66.91)]. The area under the curve was 0.93 [95% CI (0.90, 0.95)]. No obvious publication bias was found. Conclusion: Deep learning using the convolutional neural network VGGNet model based on ultrasound images performed good diagnostic efficacy in distinguishing benign and malignant thyroid nodules. Systematic Review Registration: https://www.crd.york.ac.nk/prospero, identifier CRD42022336701.

16.
Int Immunopharmacol ; 101(Pt A): 107585, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34601333

RESUMO

OBJECTIVE: Accumulating evidence has suggested that microRNAs (miRNAs) derived from M2 macrophage-derived exosomes (M2 exosomes) can regulate the progression of hepatocellular carcinoma (HCC). Nevertheless, the effect of miR-27a-3p derived from M2 exosomes on HCC has not been reported. We aim to explore the role of M2 exosomal miR-27a-3p in the cancer stemness of HCC via regulating thioredoxin-interacting protein (TXNIP). METHODS: Exosomes were extracted from transfected M2 macrophages and were then co-cultured with HCC cells. Expression of miR-27a-3p and TXNIP, stemness, proliferation, drug resistance, migration, invasion and in vivo tumorigenicity of HCC cells were determined to assess the role of M2 exosomal miR-27a-3p in HCC. The binding relationship between miR-27a-3p and TXNIP was detected. RESULTS: MiR-27a-3p was upregulated and TXNIP was downregulated in HCC cells, and M2 exosomes further upregulated miR-27a-3p. The upregulated M2 exosomal miR-27a-3p promoted stemness, proliferation, drug resistance, migration, invasion and in vivo tumorigenicity of HCC cells. TXNIP was confirmed as a target gene of miR-27a-3p. CONCLUSION: M2 macrophages-derived exosomal miR-27a-3p promotes cancer stemness of HCC via downregulating TXNIP.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Transporte/genética , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Regulação para Baixo/imunologia , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Regulação para Cima/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Cancer Commun (Lond) ; 41(2): 154-170, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33389821

RESUMO

BACKGROUND: The transforming growth factor-ß (TGF-ß) pathway plays a pivotal role in inducing epithelial-mesenchymal transition (EMT), which is a key step in cancer invasion and metastasis. However, the regulatory mechanism of TGF-ß in inducing EMT in colorectal cancer (CRC) has not been fully elucidated. In previous studies, it was found that S100A8 may regulate EMT. This study aimed to clarify the role of S100A8 in TGF-ß-induced EMT and explore the underlying mechanism in CRC. METHODS: S100A8 and upstream transcription factor 2 (USF2) expression was detected by immunohistochemistry in 412 CRC tissues. Kaplan-Meier survival analysis was performed. In vitro, Western blot, and migration and invasion assays were performed to investigate the effects of S100A8 and USF2 on TGF-ß-induced EMT. Mouse metastasis models were used to determine in vivo metastasis ability. Luciferase reporter and chromatin immunoprecipitation assay were used to explore the role of USF2 on S100A8 transcription. RESULTS: During TGF-ß-induced EMT in CRC cells, S100A8 and the transcription factor USF2 were upregulated. S100A8 promoted cell migration and invasion and EMT. USF2 transcriptionally regulated S100A8 expression by directly binding to its promoter region. Furthermore, TGF-ß enhanced the USF2/S100A8 signaling axis of CRC cells whereas extracellular S100A8 inhibited the USF2/S100A8 axis of CRC cells. S100A8 expression in tumor cells was associated with poor overall survival in CRC. USF2 expression was positively related to S100A8 expression in tumor cells but negatively related to S100A8-positive stromal cells. CONCLUSIONS: TGF-ß was found to promote EMT and metastasis through the USF2/S100A8 axis in CRC while extracellular S100A8 suppressed the USF2/S100A8 axis. USF2 was identified as an important switch on the intracellular and extracellular S100A8 feedback loop.


Assuntos
Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Animais , Calgranulina A/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Fator de Crescimento Transformador beta/metabolismo , Fatores Estimuladores Upstream
19.
Environ Sci Pollut Res Int ; 28(1): 16-34, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33009615

RESUMO

Water pollution is a global environmental problem that affects the ecosystem severely. Treatment of oily wastewater and organic pollutants is a major challenge that waits to be solved as soon as possible. Adsorbing is one of the most effective strategies to deal with this problem. Three-dimensional (3D) porous adsorbents made of graphene or graphene-based nanomaterials skeletons had attracted more attention in wastewater treatment because of their large surface area, high porosity, low density, high chemical/thermal stability, and steady mechanical properties, which allow different pollutants to easily access and diffuse into 3D networks of adsorbents. This work presents an extensive summarization of recent progress in the synthesis methodologies and microstructures of 3D graphene foams and 3D graphene-based foams and highlights their adsorption performance for oils and organic solvents. Advantages and disadvantages of various preparation strategies are compared and the corresponded structures of these skeletons are studied in detail. Furthermore, the effects of the structures on oil-adsorption properties are analyzed and some data and parameters of the oil-adsorption properties are listed and studied for easier comparison. At last, the future research directions and technical challenges are prospected, which is hoped that the researchers will be inspired to develop the new graphene-based adsorbents.


Assuntos
Grafite , Poluentes Químicos da Água , Adsorção , Ecossistema , Óleos , Esqueleto/química , Águas Residuárias , Poluentes Químicos da Água/análise
20.
Cancer Manag Res ; 12: 8685-8693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061567

RESUMO

INTRODUCTION: MicroRNAs (miRNAs) are key modulators for gene expression via inducing translational repression or target gene degradation. miR-133a-3p was reported to stimulate or inhibit cancer progression but its role in hepatocellular carcinoma (HCC) remains to be explored. METHODS: Quantitative real-time PCR (RT-qPCR) was utilized to explore miR-133a-3p expression level in HCC cells. Dual-luciferase activity reporter assay was used to validate the direct interaction between miR-133a-3p and coronin-like actin-binding protein 1C (CORO1C). In addition, we analyzed the expression levels of miR-133a-3p and CORO1C in HCC tissues and normal tissues on the UCALAN website. Functional assays including cell counting kit-8 assay, colony formation assay, flow cytometry analysis and transwell invasion assay were conducted to explore the biological functions of miR-133a-3p in HCC. RESULTS: miR-133a-3p was found to have downregulated expression in HCC tissues and cells. Meanwhile, we showed that low miR-133a-3p levels were correlated with poorer overall survival of HCC patients. Overexpression of miR-133a-3p suppressed HCC cell growth and invasion but promoted cell apoptosis via targeting CORO1C. DISCUSSION: Our results revealed a novel mechanism of miR-133a-3p in regulating HCC progression and provided evidence that miR-133a-3p functions as a tumor suppressor in HCC.

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