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Gelatin, a protein derivative from collagen, is a versatile material with promising applications in tissue engineering. Among the various forms of gelatin scaffolds, nanofibrous gelatin microspheres (NFGMs) are attracting research efforts due to their fibrous nature and injectability. However, current methods for synthesizing nanofibrous gelatin microspheres (NFGMs) have limitations, such as wide size distributions and the use of toxic solvents. To address these challenges, the article introduces a novel approach. First, it describes the creation of a microfluidic device using readily available supplies. Subsequently, it outlines a unique process for producing monodispersed NFGMs through a combination of the microfluidic device and thermally induced phase separation (TIPS). This innovative method eliminates the need for sieving and the use of toxic solvents, making it a more ecofriendly and efficient alternative.
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Gelatina , Microesferas , Nanofibras , Gelatina/química , Nanofibras/química , Engenharia Tecidual/métodos , Microfluídica/métodos , Microfluídica/instrumentação , Alicerces Teciduais/química , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodosRESUMO
Low-coverage whole genome sequencing was performed for tissue samples from thyroid patients who received surgery treatment from 2015 to 2021. The potential biological significance of CD147 protein in thyroid cancer was explored through correlation analysis of CD147 protein expression level and clinical features of thyroid cancer patients. Low coverage whole genome sequencing was performed on the extracted DNA samples. The copy number analysis software was used to analyze the sequencing data, calculate the copy number of CD147 gene, further verify the expression of CD147 gene, and analyze its association with clinical features. The relationship between CIN and high risk was evaluated in the internal cohort. The association of CIN with the disease-free survival was validated in the cohort from The Cancer Genome Atlas Program. Thyroglobulin plays a key role in regulating thyroid function and maintaining normal metabolic rate. By sequencing tissue samples from this study, we can gain a deeper understanding of the association between cin and thyroid disease. The percentage of high risk patients in the multiple CIN group (77.8 %) was significantly higher than that in the 22q negative group (31.3 %), BRAF V600E group (22.2 %) and all negative group (25.0 %; p = 0.043).
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Basigina , Instabilidade Cromossômica , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Basigina/genética , Basigina/metabolismo , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Adulto , Biomarcadores Tumorais/genética , Sequenciamento Completo do GenomaRESUMO
Esophageal cancer is one of the most common malignant tumors, and the 5-year overall survival rate is only 20%. Esophageal squamous cell carcinoma (ESCC) is the primary histological type of esophageal carcinoma in China. Protein phosphatase 1 regulatory subunit 18 (PPP1r18) is one of the actin-regulatory proteins and is able to bind to protein phosphatase 1 catalytic subunit alpha (PPP1CA). Yet, little is known about the role of PPP1r18 in esophageal squamous cell carcinoma (ESCC). This study aimed to elucidate the biological functions of PPP1r18 in the ESCC progression. Clinical samples first confirmed that PPP1r18 expression was upregulated in ESCC, and PPP1r18 was correlated with tumor invasion depth, lymph node metastasis, distant metastasis, and reduced overall survival. We then observed that PPP1r18 overexpression enhanced cell proliferation in vitro and in vivo. Mechanistically, PPP1r18 regulated tumor progression of ESCC through activating the calcineurin-mediated ERK pathway, rather than binding to PPP1CA. Collectively, our results suggest that PPP1r18 promotes ESCC progression by regulating the calcineurin-mediated ERK pathway. PPP1r18 might be a potential target for the diagnosis and treatment of ESCC.
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BACKGROUND: Breast cancer is one of the common malignancies in women. Evidence has demonstrated that FBXO45 plays a pivotal role in oncogenesis and progression. However, the role of FBXO45 in breast tumorigenesis remains elusive. Exploration of the regulatory mechanisms of FBXO45 in breast cancer development is pivotal for potential therapeutic interventions in patients with breast cancer. METHODS: Hence, we used numerous approaches to explore the functions of FBXO45 and its underlaying mechanisms in breast cancer pathogenesis, including CCK-8 assay, EdU assay, colony formation analysis, apoptosis assay, RT-PCR, Western blotting, immunoprecipitation, ubiquitination assay, and cycloheximide chase assay. RESULTS: We found that downregulation of FBXO45 inhibited cell proliferation, while upregulation of FBXO45 elevated cell proliferation in breast cancer. Silencing of FBXO45 induced cell apoptosis, whereas overexpression of FBXO45 inhibited cell apoptosis in breast cancer. Moreover, FBXO45 interacted with BIM and regulated its ubiquitination and degradation. Furthermore, knockdown of FBXO45 inhibited cell proliferation via regulation of BIM pathway. Notably, overexpression of FBXO45 facilitated tumor growth in mice. Strikingly, FBXO45 expression was associated with poor survival of breast cancer patients. CONCLUSION: Our study could provide the rational for targeting FBXO45 to obtain benefit for breast cancer patients. Altogether, modulating FBXO45/Bim axis could be a promising strategy for breast cancer therapy.
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Apoptose , Proteína 11 Semelhante a Bcl-2 , Neoplasias da Mama , Proliferação de Células , Progressão da Doença , Proteínas F-Box , Ubiquitinação , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Feminino , Animais , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Camundongos , Proteína 11 Semelhante a Bcl-2/metabolismo , Proteína 11 Semelhante a Bcl-2/genética , Linhagem Celular Tumoral , Proteólise , Regulação Neoplásica da Expressão Gênica , Camundongos NusRESUMO
Esophageal squamous cell carcinoma stands as a notably aggressive malignancy within the digestive system. In cases of early esophageal cancer without lymph node metastasis, endoscopic surgical resection offers a viable alternative, often resulting in improved patient quality of life. However, the paucity of methods to preoperatively ascertain lymph node involvement complicates surgical planning. SOX4 gene was previously found to be highly associated with invasive metastasis in our work through single-cell RNA sequencing on 5 paired tumor/peritumor tissues. This research included the collection of 124 tissue samples from 106 patients (106 tumor and 18 lymph node specimens). Samples were methodically arranged into a tissue microarray and treated with immunohistochemical staining. Statistical analysis was conducted to assess the relationship between them. In the univariate analysis, 3 factors were identified as statistically significant in relation to lymph node metastasis: T category (P = .014), vascular invasion (P < .001), and SOX4 intensity (P = .001). Additionally, when evaluating SOX4 intensity alongside other clinical indicators, SOX4 was shown to independently influence lymph node metastasis. Further, the multivariate analysis revealed that vascular invasion (P < .001) and SOX4 intensity (P = .003) were significantly associated with lymph node metastasis, exhibiting hazard ratios of 10.174 and 7.142, respectively. The results of our study indicate that both SOX4 expression and vascular invasion serve as predictors of lymph node metastasis in patients diagnosed with category T1 esophageal squamous cell carcinoma, underscoring the potential utility of SOX4 in prognostic evaluations.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Metástase Linfática , Fatores de Transcrição SOXC , Feminino , Humanos , Masculino , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/secundário , Carcinoma de Células Escamosas do Esôfago/cirurgia , Linfonodos/patologia , Linfonodos/metabolismo , Prognóstico , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição SOXC/genéticaRESUMO
BACKGROUND: Differentiating seminomas from nonseminomas is crucial for formulating optimal treatment strategies for testicular germ cell tumors (TGCTs). Therefore, our study aimed to develop and validate a clinical-radiomics model for this purpose. METHODS: In this study, 221 patients with TGCTs confirmed by pathology from four hospitals were enrolled and classified into training (n = 126), internal validation (n = 55) and external test (n = 40) cohorts. Radiomics features were extracted from the CT images. After feature selection, we constructed a clinical model, radiomics models and clinical-radiomics model with different machine learning algorithms. The top-performing model was chosen utilizing receiver operating characteristic (ROC) curve analysis. Decision curve analysis (DCA) was also conducted to assess its practical utility. RESULTS: Compared with those of the clinical and radiomics models, the clinical-radiomics model demonstrated the highest discriminatory ability, with AUCs of 0.918 (95 % CI: 0.870 - 0.966), 0.909 (95 % CI: 0.829 - 0.988) and 0.839 (95 % CI: 0.709 - 0.968) in the training, validation and test cohorts, respectively. Moreover, DCA confirmed that the combined model had a greater net benefit in predicting seminomas and nonseminomas. CONCLUSION: The clinical-radiomics model serves as a potential tool for noninvasive differentiation between testicular seminomas and nonseminomas, offering valuable guidance for clinical treatment.
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Aprendizado de Máquina , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/diagnóstico por imagem , Seminoma/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Adulto Jovem , Reprodutibilidade dos Testes , RadiômicaRESUMO
Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA). Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development. Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down. Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA.
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Carcinoma , Neoplasias Esofágicas , Humanos , Prognóstico , Oncogenes , Linfócitos B , Neoplasias Esofágicas/genética , Biomarcadores , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
Artificial per- and polyfluoroalkyl substances (PFASs) are widely distributed in the environment and are potentially harmful to human health. This study assessed the matrix effect of different shellfish on LC-MS analysis and the recoveries of PFASs in purified extracts purified by adding ENVI-Carb graphitized carbon black. Total 76 samples were collected from coastal cities of the Bohai Sea and South China Sea in China. Results showed that the signal response of perfluorocarboxylic acid increased with the length of fluorocarbon chains. ENVI-Carb can mitigate the shellfish matrix effects for analysis of PFASs. Ten PFASs components were detected in shellfish samples at concentrations ranging from 1.3 to 8.5 ng/g wet weight. The PFOA and PFHxS were the dominant components, and PFOA, PFTrDA and PFNA were detected at high rates of 58-93%. The highest levels of ∑PFASs were accumulated in clams, while the lowest levels were found in mussels. The dietary risk assessment indicated that PFASs potentially threaten human health via consumption of clam products in the Bohai Sea region. This study will improve the understanding of the contamination status and the dietary risk of PFASs in shellfish products along the coasts of Bohai Sea and South China Sea in China.
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Ácidos Alcanossulfônicos , Bivalves , Fluorocarbonos , Poluentes Químicos da Água , Animais , Humanos , Poluentes Químicos da Água/análise , Frutos do Mar/análise , Alimentos Marinhos/análise , China , Fluorocarbonos/análise , Monitoramento Ambiental/métodos , Ácidos Alcanossulfônicos/análiseRESUMO
We included 39 studies in our meta-analysis, finding that patients with ankylosing spondylitis (AS) exhibit decreased bone mineral density (BMD) and an elevated risk of fractures. Additionally, we analyzed the risk factors associated with fractures in these patients. INTRODUCTION: AS is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints, with reduced BMD, osteoporosis, and fractures being common complications. This study aims to systematically consolidate and conduct a meta-analysis of existing research to comprehensively understand decreased bone mineral density, osteoporosis, and fracture risks at various anatomical sites in AS patients. The objective is to provide reliable information for the management of AS patients and to inform clinical decision making. METHODS: We conducted a thorough search in various databases including Embase, PubMed, Cochrane Library, and Web of Science. These studies focused on the risk of and risk factors for decreased BMD, osteopenia, osteoporosis, and fractures at different sites among AS patients such as the lumbar spine and femoral neck. The quality of eligible studies was evaluated. Sensitivity analysis was performed to assess the reliability of our analysis results and understand the effects of individual studies on the heterogeneity across studies. RESULTS: A total of 39 studies were included. Our meta-analysis results revealed significant differences between AS patients and healthy controls. AS patients had significantly lower BMDs at the femoral neck, hip, lumbar vertebra 2 (L2), lumbar vertebra 3 (L3), and lumbar vertebra 4 (L4), but higher BMDs at 1/3 distal radius and ultra distal radius. Risk factors for fractures among AS patients included old age, long course of disease, and low BMD at the lumbar spine. In contrast, factors such as erythrocyte sedimentation rate (ESR), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, gender, and body mass index (BMI) were not risk factors for fractures in AS patients. CONCLUSION: Our study highlights that BMD at the femoral neck is more effective for evaluating AS patients compared with the BMD at the lumbar spine. Additionally, the risk of osteoporosis and fractures in AS patients is higher in younger patients and those at the early stage of this disease.
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Densidade Óssea , Osteoporose , Fraturas da Coluna Vertebral , Espondilite Anquilosante , Humanos , Absorciometria de Fóton , Vértebras Lombares , Osteoporose/complicações , Reprodutibilidade dos Testes , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Espondilite Anquilosante/complicaçõesRESUMO
Objective: To determine the impacts of concurrent aerobic and resistance training on vascular structure (IMT) and function (PWV, FMD, NMD) in type 2 diabetes (T2D). Methods: The electronic databases PubMed, Web of Science Core Collection, Cochrane Library, Embase, Scopus, CINAHL, and SPORTDiscus were systematically searched for articles on "type 2 diabetes" and "concurrent training" published from inception to August 2, 2022. We included randomized controlled trials that examined the effects of concurrent training versus passive controls on IMT, PWV, FMD and NMD in T2D. Results: Ten studies were eligible, including a total of 361 participants. For IMT, concurrent training showed a slight decrease by 0.05 mm (95% CI -0.11 to 0.01, p > 0.05). concurrent training induced an overall significant improvement in FMD by 1.47% (95% CI 0.15 to 2.79, p < 0.05) and PWV by 0.66 m/s (95% CI -0.89 to -0.43, p < 0.01) in type 2 diabetics. However, concurrent training seemed to exaggerate the impaired NMD (WMD = -2.30%, 95% CI -4.02 to -0.58, p < 0.05). Conclusions: Concurrent training is an effective method to improve endothelial function and artery stiffness in T2D. However, within 24 weeks concurrent training exacerbates vascular smooth muscle dysfunction. More research is needed to explore whether longer and/or higher-intensity concurrent training interventions could enhance the vascular structure and smooth muscle function in this population. Systematic review registration: www.crd.york.ac.uk/PROSPERO/, identifier CRD42022350604.
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Diabetes Mellitus Tipo 2 , Treinamento Resistido , Rigidez Vascular , Humanos , Treinamento Resistido/métodos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Exercício Físico/fisiologia , Rigidez Vascular/fisiologia , Músculo Liso VascularRESUMO
Background: Breast cancer, a type of tumor associated with high heterogeneity, is top among the common malignancies threatening women's health worldwide. Emerging evidence suggests that competing endogenous RNA (ceRNA) plays a role in the molecular biological mechanisms related to the occurrence and development of cancer. However, the effect of the ceRNA network on breast cancer, especially the long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network, has not been fully studied. Methods: To explore potential prognostic markers of breast cancer under ceRNA network, we first extracted the breast cancer expression profiles of lncRNAs, miRNAs and mRNAs and their corresponding clinical data from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) database. Next, we selected breast cancer-related candidate genes by intersection of the differential expression analysis and the weighted gene coexpression network analysis (WGCNA). Then, we studied the interactions among lncRNAs, miRNAs, and mRNAs by means of multiMiR and starBase and then constructed a ceRNA network of 9 lncRNAs, 26 miRNAs, and 110 mRNAs. We established a prognostic risk formula by means of multivariable Cox regression analysis. Results: Based on public databases and evaluated via modeling, we identified the HOX antisense intergenic RNA (HOTAIR)-miR-130a-3p-high mobility group-box 3 (HMGB3) axis as a potential prognostic marker in breast cancer through a prognostic risk model we established using multivariable Cox analysis. Conclusions: For the first time, the potential interactions among HOTAIR, miR-130a-3p, and HMGB3 in the tumorigenesis were clarified, and these may provide novel prognostic value for breast cancer treatment.
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Background: Since the discovery of rehabilitation as an intervention for rotator cuff injury, its impact on the recovery of rotator cuff injury has attracted crucial attention, and the number of related studies is increasing worldwide. There were no bibliometric and visualized analysis studies in this field. This study aimed to investigate the research hotpots and trends in the rehabilitation of rotator cuff injury via bibliometric and visualized analysis and to identify the future development of clinical practice. Method: The publications regarding rehabilitation of rotator cuff injury from inception to December 2021 were obtained from the Web of Science Core Collection database. The trends of publications, co-authorship and co-occurrence analysis and visualized analysis were carried out using Citespace, VOSviewer, Scimago Graphica software, and R Project. Results: A total of 795 publications were included in this study. The number of publications significantly increased yearly. The United States published the highest number of related papers and the papers published by the United States had the highest citations. The University of Laval, the University of Montreal and Keele University were the top 3 most contributive institutions. Additionally, the Journal of Shoulder and Elbow Surgery was the journal with the highest number of publications. The most common keywords were "rotator cuff", "rehabilitation", "physical therapy", "management", and "telerehabilitation". Conclusion: The total number of publications has shown a steady upward trend. The cooperation between countries globally was still relatively lacking, and therefore it is necessary to strengthen cooperation between different countries and regions to provide conditions for multi-center, large sample, and high-quality research. In addition to the relatively mature rehabilitation of rotator cuff injury such as passive motion or exercise therapy, telerehabilitation has also attracted much attention with the progress of science.
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Lesões do Manguito Rotador , Humanos , Terapia por Exercício , Bibliometria , Publicações , Bases de Dados FactuaisRESUMO
Objective: To investigate the effects of different puncture levels on bone cement distribution and effectiveness in bilateral percutaneous vertebroplasty for osteoporotic thoracolumbar compression fractures. Methods: A clinical data of 274 patients with osteoporotic thoracolumbar compression fractures who met the selection criteria between December 2017 and December 2020 was retrospectively analyzed. All patients underwent bilateral percutaneous vertebroplasty. During operation, the final position of the puncture needle tip reached was observed by C-arm X-ray machine. And 118 cases of bilateral puncture needle tips were at the same level (group A); 156 cases of bilateral puncture needle tips were at different levels (group B), of which 87 cases were at the upper 1/3 layer and the lower 1/3 layer respectively (group B1), and 69 cases were at the adjacent levels (group B2). There was no significant difference in gender, age, fracture segment, degree of osteoporosis, disease duration, and preoperative visual analogue scale (VAS) score, and Oswestry disability index (ODI) between groups A and B and among groups A, B1, and B2 ( P>0.05). The operation time, bone cement injection volume, postoperative VAS score, ODI, and bone cement distribution were compared among the groups. Results: All operations were successfully completed without pulmonary embolism, needle tract infection, or nerve compression caused by bone cement leakage. There was no significant difference in operation time and bone cement injection volume between groups A and B or among groups A, B1, and B2 ( P>0.05). All patients were followed up 3-32 months, with an average of 7.8 months. There was no significant difference in follow-up time between groups A and B and among groups A, B1, and B2 ( P>0.05). At 3 days after operation and last follow-up, VAS score and ODI were significantly lower in group B than in group A ( P<0.05), in groups B1 and B2 than in group A ( P<0.05), and in group B1 than in group B2 ( P<0.05). Imaging review showed that the distribution of bone cement in the coronal midline of injured vertebrae was significantly better in group B than in group A ( P<0.05), in groups B1 and B2 than in group A ( P<0.05), and in group B1 than in group B2 ( P<0.05). In group A, 7 cases had postoperative vertebral collapse and 8 cases had other vertebral fractures. In group B, only 1 case had postoperative vertebral collapse during follow-up. Conclusion: Bilateral percutaneous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures can obtain good bone cement distribution and effectiveness when the puncture needle tips locate at different levels during operation. When the puncture needle tips locate at the upper 1/3 layer and the lower 1/3 layer of the vertebral body, respectively, the puncture sites are closer to the upper and lower endplates, and the injected bone cement is easier to connect with the upper and lower endplates.
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Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Fraturas por Compressão/cirurgia , Cimentos Ósseos/uso terapêutico , Vertebroplastia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Punção Espinal , Fraturas da Coluna Vertebral/cirurgia , Fraturas por Osteoporose/cirurgiaRESUMO
BACKGROUND AND AIMS: The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single-cell level is rare due to the need for fresh and high-quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. METHODS: Five paired samples of intramucosal ESCC, para-ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. RESULTS: A total of 164 715 cells were profiled. Epithelial cells exhibited high intra-tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEX s, Tregs and PD1+ CD4+ T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand-receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK-NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. CONCLUSION: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Leucócitos Mononucleares , Transcriptoma/genética , Células Epiteliais , Neoplasias Esofágicas/genética , Microambiente Tumoral/genéticaRESUMO
Friedreich's ataxia (FRDA) is caused primarily by expanded GAA repeats in intron 1 of both alleles of the FXN gene, which causes transcriptional silencing and reduced expression of frataxin mRNA and protein. FRDA is characterized by slowly progressive ataxia and cardiomyopathy. Symptoms generally appear during adolescence, and patients slowly progress to wheelchair dependency usually in the late teens or early twenties with death on average in the 4th decade. There are two known mature proteoforms of frataxin. Mitochondrial frataxin (frataxin-M) is a 130-amino acid protein with a molecular weight of 14,268 Da, and there is an alternatively spliced N-terminally acetylated 135-amino acid form (frataxin-E) with a molecular weight of 14,953 Da found in erythrocytes. There is reduced expression of frataxin in the heart and brain, but frataxin is not secreted into the systemic circulation, so it cannot be analyzed in serum or plasma. Blood is a readily accessible biofluid that contains numerous different cell types that express frataxin. We have found that pig blood can serve as an excellent surrogate matrix to validate an assay for frataxin proteoforms because pig frataxin is lost during the immunoprecipitation step used to isolate human frataxin. Frataxin-M is expressed in blood cells that contain mitochondria, whereas extra-mitochondrial frataxin-E is found in erythrocytes. This means that the analysis of frataxin in whole blood provides information on the concentration of both proteoforms without having to isolate the individual cell types. In the current study, we observed that the distributions of frataxin levels for a sample of 25 healthy controls and 50 FRDA patients were completely separated from each other, suggesting 100% specificity and 100% sensitivity for distinguishing healthy controls from FRDA cases, a very unusual finding for a biomarker assay. Additionally, frataxin levels were significantly correlated with the GAA repeat length and age of onset with higher correlations for extra-mitochondrial frataxin-E than those for mitochondrial frataxin-M. These findings auger well for using frataxin levels measured by the validated stable isotope dilution ultrahigh-performance liquid chromatography-multiple reaction monitoring/mass spectrometry assay to monitor therapeutic interventions and the natural history of FRDA. Our study also illustrates the utility of using whole blood for protein disease biomarker discovery and validation.
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Ataxia de Friedreich , Animais , Humanos , Biomarcadores , Cromatografia Líquida , Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/genética , Espectrometria de Massas , Suínos , FrataxinaRESUMO
Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer.
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OBJECTIVE: To investigate the effect of gender transfer in virtual reality on implicit gender bias. BACKGROUND: Gender bias is a type of discrimination based on gender, which can lead to increased self-doubt and decreased self-esteem. Sexual harassment is a hostile form of gender bias that can cause anxiety, depression, and significant mental health issues. Virtual reality (VR) has been employed to help make people become aware of their biases and change their attitudes regarding gender, race, and age. METHODS: Forty participants were embodied in avatars of different genders and experienced sexual harassment scenarios in VR. A gender Implicit Association Test (IAT) was administered before and after the experience. RESULTS: There was a statistically significant main effect of participant gender (F (1,36) = 10.67, p = .002, partial η2 = .23) on ΔIAT, where males and females reported a decrease (M = -.12, SD = .24) and an increase (M = .10, SD = .25) in IAT scores, respectively. A statistically significant two-way interaction between gender transfer and participant gender was revealed (F (1,36) = 6.32, p = .02, partial η2 = .15). There was a significant simple effect of gender transfer for male participants (F (1,36) = 8.70, p = .006, partial η2 = .19). CONCLUSIONS: Implicit gender bias can be modified, at least temporarily, through embodiment in VR. Gender transfer through embodiment while encountering different sexual harassment scenarios helped reduce implicit gender bias. There was a tendency for individuals to increase bias for the gender of the avatar in which they embodied. APPLICATIONS: The current research provided promising evidence that a virtual environment system may be used as a potential training tool to improve implicit gender bias.
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Background: Papillary thyroid microcarcinoma (PTMC) is defined as a papillary carcinoma measuring ≤ 10 mm. The current management of PTMC has become more conservative; however, there are high-risk tumor features that can be revealed only postoperatively. For thyroid cancer, BRAF mutations and somatic copy number variation (CNV) are the most common genetic events. Molecular testing may contribute to clinical decision-making by molecular risk stratification, for example predicting lymph node (LN) metastasis. Here, we build a risk stratification model based on molecular profiling of thyroid fine needle aspiration (FNA) washout DNA (wDNA) for the differential diagnosis of thyroid nodules. Methods: Fifty-eight patients were recruited, FNA wDNA samples were analyzed using CNV profiling through low-coverage whole genome sequencing (LC-WGS) and BRAF mutation was analyzed using quantitative PCR. FNA pathology was reported as a Bethesda System for Reporting Thyroid Cytopathology (BSRTC) score. Ultrasound examination produced a Thyroid Imaging Reporting and Data System (TIRADS) score. Results: In total, 37 (63.8%) patients with a TIRADS score of 4A, 13 (22.4%) patients with a TIRADS score of 4B, and 8 (13.8%) patients with a TIRADS score of 4C were recruited after ultrasound examination. All patients underwent FNA with wDNA profiling. CNVs were identified in 17 (29.3%) patients. CNVs were frequent in patients with a BSRTC score of V or VI, including eight (47.1%) patients with a score of VI and five (29.4%) with a score of V, but not in patients with a score of III, II, or I (0%). BRAF mutation was not significantly correlated with BSRTC score. LN metastasis was found more frequently in CNV-positive (CNV+) than in CNV-negative (CNV-) patients (85.7% vs. 34.6%, odds ratio = 11.33, p = 0.002). In total, three molecular subtypes of thyroid nodules were identified in this study: 1) CNV+, 2) CNV- and BRAF positive (BRAF+), and 3) CNV- and BRAF negative (BRAF-). For the CNV+ subtype, 10 (83.3%) lesions with LN metastasis were found, including four (100%) small lesions (i.e. ≤ 5 mm). For the CNV- and BRAF+ nodules, LN metastases were detected in only seven (60.0%) larger tumors (i.e. > 5 mm). For CNV- and BRAF- tumors, LN metastasis was also frequently found in larger tumors only. Conclusions: It is feasible to identify high-risk LN metastasis thyroid cancer from FNA washout samples preoperatively using wDNA CNV profiling using LC-WGS.
Assuntos
Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Metástase Linfática , Sequenciamento Completo do Genoma , DNARESUMO
BACKGROUND AND AIM: Developments of endoscopic techniques brought the possibility of endoscopic resection for gastrointestinal stromal tumors (GISTs) of larger sizes. We aim to compare safety and short-term outcomes between endoscopic and laparoscopic resections of gastric GISTs with a diameter of 2-5 cm. METHODS: This is a single-center, retrospective cohort study. The clinical data, perioperative conditions, and the adverse events of patients who underwent endoscopic or laparoscopic resection for gastric GIST of 2-5 cm in Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were retrospectively reviewed. RESULTS: A total of 346 patients were reviewed; 12 patients who failed to accomplish the planned procedure were excluded; 182 underwent laparoscopic resection; and 152 underwent endoscopic resection. Significant differences exist in the tumor size between the laparoscopic group (3.43 ± 0.86 cm) and the endoscopic group (2.78 ± 0.73 cm) (P < 0.01). Compared with laparoscopic resection, endoscopic resection was associated with faster recovery (P < 0.01), shorter hospital stays (P < 0.01), and lower cost (P < 0.01). The incidence of Clavien-Dindo grade II-V adverse events in the endoscopic group (3/152) was significantly lower than that in the laparoscopic group (12/182) (P = 0.04). After a propensity score matching analysis, the endoscopic group showed similar incidences of complications with the laparoscopic group, while the advantages over laparoscopic resection in postoperative hospital stay, time to first oral intake, and hospitalization expenses remained significant (P < 0.01). CONCLUSIONS: Endoscopic resection is a safe and cost-effective method for 2-5 cm of gastric GISTs compared with laparoscopic resection.
Assuntos
Tumores do Estroma Gastrointestinal , Laparoscopia , Neoplasias Gástricas , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de Internação , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
PURPOSE: To investigate the potential of adding silver-nanoparticle-containing amorphous calcium phosphate microparticles as bioactive fillers into commercially available nonbioactive dental resin cement. MATERIALS AND METHODS: Experimental cement was formulated by adding 7.5% silver-nanoparticle-containing amorphous calcium phosphate microparticles to Multilink Automix resin cement (Ivoclar Vivadent). The experimental cement was evaluated for shear bond strength (N = 11 per group) and demineralization/remineralization (N = 16 per group), with BioCem® Universal BioActive cement (NuSmile) as the positive control and Multilink Automix cement as the negative control. One-way analysis of variance and post hoc tests were used to assess the significance of differences among or between the groups RESULTS: The addition of silver-nanoparticle-containing amorphous calcium phosphate microparticles at the level of 7.5% by weight into Multilink Automix did not have a statistically significant effect on the shear bond strength (p > 0.05), but statistically significantly increased the depth of remineralization on both dentin and enamel (p = 0.01 and p < 0.001, respectively) when compared to Multilink Automix alone. The experimental cement prepared in the present study was comparable to BioCem® on the depths of remineralization on both dentin and enamel (p = 0.59 and p = 0.99, respectively). CONCLUSION: When incorporated into nonbioactive commercial dental resin cements as bioactive fillers at the level of 7.5% by weight, silver-nanoparticle-containing amorphous calcium phosphate microparticles could provide remineralization potential without affecting the shear bond strength.