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Cancer remains a leading cause of mortality and poses a substantial threat to public health. Studies have revealed that Long noncoding RNA DANCR is a cytoplasmic lncRNA whose aberrant expression plays a pivotal role in various cancer types. Within tumour biology, DANCR exerts regulatory control over crucial processes such as proliferation, invasion, metastasis, angiogenesis, inflammatory responses, cellular energy metabolism reprogramming, and apoptosis. By acting as a competitive endogenous RNA for miRNAs and by interacting with proteins and mRNAs at the molecular level, DANCR contributes significantly to cancer progression. Elevated DANCR levels have also been linked to heightened resistance to anticancer drugs. Moreover, the detection of circulating DANCR holds promise as a valuable biomarker for aiding in the clinical differentiation of different cancer types. This article offers a comprehensive review and elucidation of the primary functions and molecular mechanisms through which DANCR influences tumours.
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Regulação Neoplásica da Expressão Gênica , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , AnimaisRESUMO
Radiomics and machine learning have been extensively utilized in the realm of urinary stones, particularly in forecasting stone treatment outcomes. The objective of this study was to integrate clinical variables and radiomic features to develop a machine learning model for predicting the stone-free rate (SFR) following percutaneous nephrolithotomy (PCNL). A total of 212 eligible patients who underwent PCNL surgery at the Second Affiliated Hospital of Nanchang University were included in a retrospective analysis. Preoperative clinical variables and non-contrast-enhanced CT images of all patients were collected, and radiomic features were extracted after delineating the stone ROI. Univariate analysis was conducted to identify clinical variables strongly correlated with the stone-free rate after PCNL, and the least absolute shrinkage and selection operator algorithm (lasso regression) was utilized to screen radiomic features. Four supervised machine learning algorithms, including Logistic Regression, Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Gradient Boosting Decision Tree (GBDT), were employed. The clinical variables with strong correlation and screened radiomic features were integrated into the four machine learning algorithms to construct a prediction model, and the receiver operating curve was plotted. The area under the receiver operating curve (AUC), the accuracy rate, the specificity, etc., were used to evaluate the predictive performance of the four models. After analyzing postoperative statistics, the stone-free rate following the procedure was found to be 70.3% (n = 149). Among the various clinical variables examined, factors, such as stone number, stone diameter, stone CT value, stone location, and history of stone surgery, were identified as statistically significant in relation to the stone-free rate after PCNL. A total of 121 radiomic features were extracted, and through lasso regression, 7 features most closely associated with the stone-free rate post-PCNL were identified. The predictive accuracy of different models (Logistic Regression, RF, XGBoost, and GBDT) for determining the stone-free rate after PCNL was evaluated, yielding accuracies of 78.1%, 76.6%, 75.0%, and 73.4%, respectively. The corresponding area under the curve AUC (95%CI) were 0.85 (0.83-0.89), 0.81 (0.76-0.85), 0.82 (0.78-0.85), and 0.77 (0.73-0.81), positioning these models among the top performers in logistic regression prediction. In terms of predictive importance scores, the key factors identified by the logistic regression model were number of stone, zone percentage, stone diameter, and surface area. Similarly, the RF model highlighted number of stone, stone CT value, stone diameter, and surface area as the top predictors. Among the four machine learning models, the logistic regression model demonstrated the highest accuracy and discrimination ability in predicting the stone-free rate following PCNL. In comparison to XGBoost and GBDT, RF also exhibited superior accuracy and a certain level of discrimination ability. However, based on the performance of all four models, logistic regression is more likely to aid in clinical decision-making by assisting clinicians in diagnosing PCNL in patients. This enables us to effectively predict the presence of residual stones post-surgery and ultimately select patients who are suitable candidates for PCNL.
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Nefrolitotomia Percutânea , Cálculos Urinários , Humanos , Radiômica , Estudos Retrospectivos , Aprendizado de MáquinaRESUMO
The transcription factor receptor-interacting protein 140 (RIP140) regulates intestinal homeostasis and tumorigenesis through Wnt signaling. In this study, we investigated its effect on the Notch/HES1 signaling pathway. In colorectal cancer (CRC) cell lines, RIP140 positively regulated HES1 gene expression at the transcriptional level via a recombining binding protein suppressor of hairless (RBPJ)/neurogenic locus notch homolog protein 1 (NICD)-mediated mechanism. In support of these in vitro data, RIP140 and HES1 expression significantly correlated in mouse intestine and in a cohort of CRC samples, thus supporting the positive regulation of HES1 gene expression by RIP140. Interestingly, when the Notch pathway is fully activated, RIP140 exerted a strong inhibition of HES1 gene transcription controlled by the level of HES1 itself. Moreover, RIP140 directly interacts with HES1 and reversed its mitogenic activity in human CRC cells. In line with this observation, HES1 levels were associated with a better patient survival only when tumors expressed high levels of RIP140. Our data identify RIP140 as a key regulator of the Notch/HES1 signaling pathway, with a dual effect on HES1 gene expression at the transcriptional level and a strong impact on colon cancer cell proliferation.
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Proliferação de Células , Neoplasias do Colo , Regulação Neoplásica da Expressão Gênica , Proteína 1 de Interação com Receptor Nuclear , Fatores de Transcrição HES-1 , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Proteína 1 de Interação com Receptor Nuclear/metabolismo , Receptores Notch/metabolismo , Receptores Notch/genética , Transdução de Sinais , Fatores de Transcrição HES-1/metabolismo , Fatores de Transcrição HES-1/genéticaRESUMO
This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA_07227 and circRNA_11464 in the aorta of AS model and circRNA expression(such as circRNA_11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS_00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.
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Aterosclerose , Infarto do Miocárdio , RNA Longo não Codificante , Animais , Masculino , Camundongos , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Lipídeos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , RNA Circular/genética , RNA Longo não Codificante/genéticaRESUMO
Microscopy is being pursued to obtain richer and more accurate information, and there are many challenges in imaging depth and display dimension. In this paper, we propose a three-dimensional (3D) microscope acquisition method based on a zoom objective. It enables 3D imaging of thick microscopic specimens with continuous adjustable optical magnification. The zoom objective based on liquid lenses can quickly adjust the focal length, to expand the imaging depth and change the magnification by adjusting the voltage. Based on the zoom objective, an arc shooting mount is designed to accurately rotate the objective to obtain the parallax information of the specimen and generate parallax synthesis images for 3D display. A 3D display screen is used to verify the acquisition results. The experimental results show that the obtained parallax synthesis images can accurately and efficiently restore the 3D characteristics of the specimen. The proposed method has promising applications in industrial detection, microbial observation, medical surgery, and so on.
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Black pepper essential oil has the same disadvantages as other plant essential oils, such as volatilization, high sensitivity to light and heat and poor water solubility, which leads to great limitations in application. This study improved the stability and antibacterial properties of black pepper essential oil (BPEO) based on a nano-emulsification process. Tween 80 was selected as the emulsifier to prepare the BPEO nanoemulsion. Gas chromatograph - mass spectrometer (GC-MS) was used to analyze the composition of BPEO, of which d-limonene was the main component (37.41%). After emulsification, black pepper nanoemulsion was obtained (droplet size was 11.8 nm). The water solubility and stability of the emulsions at 25 °C were also improved with decreasing particle size. Antimicrobial properties of plant pathogens (Colletotrichum gloeosporioides, Botryodiplodia theobromae) and foodborne pathogens (Staphylococcus aureus, Escherichia coli) were evaluated by disk diffusion and other techniques for determining minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). With 12.5 mg mL-1 MIC and 25 mg mL-1 MBC, BPEO inhibited the growth of two tested plant pathogens and two foodborne pathogens. Essential oils (EO) were encapsulated in a nanoemulsion system to enhance the bacteriostatic effect of essential oils and reduce MIC and MBC concentrations. After emulsification, the biological activity (antimicrobial and antioxidant) of the BPEO nanoemulsion was considerably improved, nano-emulsification had certain significance for the study of EOs.
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Skin thickness is closely related to the appearance of human skin, such as sagging and wrinkling, which primarily depends on the level of collagen I synthesized by fibroblasts in the dermal layer. To explore the underlying genetics of the development of skin thickness, we used the indigenous Chinese Chenghua pigs, considered to have superior skin thickness, as model animals. We first performed whole transcriptome sequencing analysis to identify significant skin morphological differences between Chenghua pigs and Large White pigs and obtained some differentially expressed coding RNAs (454 mRNAs) and noncoding RNAs (612 circRNAs, 188 miRNAs, and 19 lncRNAs); moreover, some competing endogenous RNA (ceRNA) networks were constructed. Interestingly, we then identified a circRNA, namely circ0044633, which plays an important role in promoting fibroblast proliferation along with myofibroblast transition and collagen I synthesis by sponging miR-23b and regulating CADM3 and MAP4K4 expression via activation of the downstream AKT and ERK pathways in vitro. Furthermore, overexpression of circ004463 increased the mouse skin thickness and collagen I content in vivo. These results revealed a whole transcript profile of skin tissue and identified an important circ0044633-miR-23b-CADM3/MAP4K4 axis related to fibroblast proliferation and collagen I synthesis during the development of skin thickness.
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MicroRNAs , RNA Longo não Codificante , Humanos , Animais , Camundongos , Suínos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sistema de Sinalização das MAP Quinases , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Longo não Codificante/genética , Proliferação de Células/genética , Fibroblastos/metabolismo , Colágeno/metabolismo , Redes Reguladoras de Genes , Proteínas Serina-Treonina Quinases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Imunoglobulinas/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismoRESUMO
BACKGROUND: Circulating long noncoding RNAs (lncRNAs) are considered a new class of biomarkers for the diagnosis and prognosis of various malignancies. We aimed to identify circulating lncRNAs as biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). METHODS: The expression of 14 candidate lncRNAs was measured in matched cancer and ipsilateral normal lung tissues of 20 patients with NSCLC using quantitative reverse-transcription PCR. In plasma samples from training and testing sets, significantly and aberrantly expressed lncRNAs, TA73-AS1 and CRNDE, were further analyzed. Receiver operating characteristic (ROC) curves were constructed, and the areas under the ROC curves (AUC) were obtained to assess diagnostic performance. The Kaplan-Meier survival analysis was used to assess the impact of plasma TA73-AS1 and CRNDE expression on tumor-free survival (TFS) of patients with NSCLC. The effect of TP73-AS1 expression on NSCLC cells was investigated in vitro. RESULTS: AUC values of plasma TA73-AS1 and CRNDE were 0.822 and 0.815 in the training set and 0.843 and 0.804 in the testing set, respectively, to distinguish NSCLC from healthy controls. The combination of plasma TP73-AS1, CRNDE, and two classical tumor markers, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1), showed excellent diagnostic performance for NSCLC (AUC =0.927 in the training set; AUC = 0.925 in the testing set). Furthermore, the high expression of the two plasma lncRNAs correlated with worse TFS in patients with NSCLC. In vitro cell model studies revealed that TP73-AS1 overexpression facilitated NSCLC cell survival, invasion, and migration. CONCLUSION: Circulating TP73-AS1 and CRNDE could be potential biomarkers for the diagnosis and prognostic prediction of NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Prognóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Biomarcadores Tumorais , Regulação Neoplásica da Expressão GênicaRESUMO
Background: Nano drug delivery system (NDDS) can significantly improve the delivery and efficacy of drugs against pancreatic cancer (PC) in many ways. The purpose of this study is to explore the related research fields of NDDS for PC from the perspective of bibliometrics. Methods: Articles and reviews on NDDS for PC published between 2003 and 2022 were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel were comprehensively used for bibliometric and visual analysis. Results: A total of 1329 papers on NDDS for PC were included. The number of papers showed an upward trend over the past 20 years. The United States contributed the most papers, followed by China, and India. Also, the United States had the highest number of total citations and H-index. The institution with the most papers was Chinese Acad Sci, which was also the most important in international institutional cooperation. Professors Couvreur P and Kazuoka K made great achievements in this field. JOURNAL OF CONTROLLED RELEASE published the most papers and was cited the most. The topics related to the tumor microenvironment such as "tumor microenvironment", "tumor penetration", "hypoxia", "exosome", and "autophagy", PC treatment-related topics such as "immunotherapy", "combination therapy", "alternating magnetic field/magnetic hyperthermia", and "ultrasound", and gene therapy dominated by "siRNA" and "miRNA" were the research hotspots in the field of NDDS for PC. Conclusion: This study systematically uncovered a holistic picture of the performance of NDDS for PC-related literature over the past 20 years. We provided scholars to understand key information in this field with the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.
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BACKGROUND: T1b gallbladder carcinoma (GBC) is defined as a tumor that invades the perimuscular connective tissue without extension beyond the serosa or into the liver. However, controversy still exists over whether patients with T1b GBC should undergo cholecystectomy alone or radical GBC resection. AIM: To explore the optimal surgical approach in patients with T1b gallbladder cancer of different pathological grades. METHODS: Patients with T1bN0M0 GBC who underwent surgical treatment between 2000 and 2017 were included in the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method and log-rank test were used to analyze the overall survival (OS) and disease-specific survival (DSS) of patients with T1b GBC of different pathological grades. Cox regression analysis was used to identify independent predictors of mortality and explore the selection of surgical methods in patients with T1b GBC of different pathological grades and their relationship with prognosis. RESULTS: Of the 528 patients diagnosed with T1bN0M0 GBC, 346 underwent simple cholecystectomy (SC) (65.5%), 131 underwent SC with lymph node resection (SC + LN) (24.8%), and 51 underwent radical cholecystectomy (RC) (9.7%). Without considering the pathological grade, both the OS (P < 0.001) and DSS (P = 0.003) of T1b GBC patients who underwent SC (10-year OS: 27.8%, 10-year DSS: 55.1%) alone were significantly lower than those of patients who underwent SC + LN (10-year OS: 35.5%, 10-year DSS: 66.3%) or RC (10-year OS: 50.3%, 10-year DSS: 75.9%). Analysis of T1b GBC according to pathological classification revealed no significant difference in OS and DSS between different types of procedures in patients with grade I T1b GBC. In patients with grade II T1b GBC, obvious survival improvement was observed in the OS (P = 0.002) and DSS (P = 0.039) of those who underwent SC + LN (10-year OS: 34.6%, 10-year DSS: 61.3%) or RC (10-year OS: 50.5%, 10-year DSS: 78.8%) compared with those who received SC (10-year OS: 28.1%, 10-year DSS: 58.3%). Among patients with grade III or IV T1b GBC, SC + LN (10-year OS: 48.5%, 10-year DSS: 72.2%), and RC (10-year OS: 80%, 10-year DSS: 80%) benefited OS (P = 0.005) and DSS (P = 0.009) far more than SC (10-year OS: 20.1%, 10-year DSS: 38.1%) alone. CONCLUSION: Simple cholecystectomy may be an adequate treatment for grade I T1b GBC, whereas more extensive surgery is optimal for grades II-IV T1b GBC.
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Neoplasias da Vesícula Biliar , Linfoma Folicular , Colecistectomia/efeitos adversos , Colecistectomia/métodos , Neoplasias da Vesícula Biliar/patologia , Humanos , Excisão de Linfonodo , Linfoma Folicular/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
Background: Stewart-Treves syndrome (STS) is a lymphatic sarcoma secondary to chronic lymphedema of the extremities. Most STS patients have a history of breast cancer and have undergone radical mastectomy and postoperative radiation and chemotherapy. It usually occurs 11 to 12 years after surgery, and about 0.45% of patients are estimated to have the disease. The characteristics of STS include that it is clinically relatively rare, has a high degree of malignancy, can spread easily in the absence of timely treatment, and has low survival rate. Herein, we report a case of STS which developed 13 years after breast cancer-related lymphoedema (BCRL). It allows doctors to recognize and detect the disease earlier. Case Description: A 74-year-old woman had undergone modified radical mastectomy 13 years ago for invasive ductal breast cancer in her left breast. After multiple rounds of postoperative chemoradiotherapy, multiple purple lesions were found in the left upper limb during physical examination in April 2021. The lesions spread rapidly and were varied in size. An immediate skin biopsy reported the lesions as STS. The patient was diagnosed with lymphangiosarcoma with metastasis (STS). The surgical method was shoulder joint amputation, chest wall resection, and local flap transfer. After surgery, the patient underwent 6 rounds of paclitaxel 300 mg + carboplatin 300 mg chemotherapy. After chemotherapy, the patient's wound healed and the suspected metastasis disappeared. At the time of writing, she has survived for more than 13 months, and her quality of life has improved significantly, to the satisfaction of the patient and her family. The patient is able to eat normally and lead a normal life with some assistance, without significant weight loss. Conclusions: Although rare, STS is a serious invasive complication of breast cancer surgery. To increase their relative survival time, patients with BCRL need to identify and thoroughly investigate rapidly progressing skin lesions, and undergo timely surgery.
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The accurate detection of colorectal cancer (CRC) at its initial stage can reduce mortality. However, the broad application of endoscopy has been limited due to the invasive procedure and patient noncompliance. Liquid biopsy with subsequent mapping of methylation in specific cell-free DNA (cfDNA) may represent an alternative approach for early diagnosis. In this study, we have developed a minimal-invasive blood-based test for detection of precancerous lesions and early-stage CRC. Using TCGA M450K methylation data, we identified candidate methylation sites with the highest Fold Change (FC) for three genes (SEPTIN9, SDC2 and VIM), which were selected from previous studies. Based on logistic regression models, we developed a 3-gene methylation signature for CRC diagnosis with high accuracy (Sensitivity =0.959, Specificity =1, AUC =0.997). Using independent public databases and data from blood samples, this model has demonstrated superior performance. The AUC was 0.919-1 and 0.905-0.916 in public tissue database for CRC and blood sample data, respectively. Thus, our proposed 3-gene methylation signature has a more reliable performance than other methods. Furthermore, signal enhancement effect of 3-gene methylation signature can improve the accuracy of early diagnosis for CRC, which demonstrates the potential for clinical application.
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BACKGROUND: Mucopolysaccharidosis II (MPS II) is an X-linked disorder resulting from a deficiency in lysosomal enzyme iduronate-2-sulfatase (IDS), which causes the accumulation of glycosaminoglycans (GAGs) in the lysosomes of many tissues and organs, leading to progressive cellular dysfunction. An MPS II newborn screening program has been available in Taiwan since 2015. The aim of the current study was to collect and analyze the long-term follow-up data of the screen-positive subjects in this program. METHODS: From August 2015 to April 2022, 548,624 newborns were screened for MPS II by dried blood spots using tandem mass spectrometry, of which 202 suspected infants were referred to our hospital for confirmation. The diagnosis of MPS II was confirmed by IDS enzyme activity assay in leukocytes, quantitative determination of urinary GAGs by mass spectrometry, and identification of the IDS gene variant. RESULTS: Among the 202 referred infants, 10 (5%) with seven IDS gene variants were diagnosed with confirmed MPS II (Group 1), 151 (75%) with nine IDS gene variants were classified as having suspected MPS II or pseudodeficiency (Group 2), and 41 (20%) with five IDS gene variants were classified as not having MPS II (Group 3). Long-term follow-up every 6 months was arranged for the infants in Group 1 and Group 2. Intravenous enzyme replacement therapy (ERT) was started in four patients at 1, 0.5, 0.4, and 0.5 years of age, respectively. Three patients also received hematopoietic stem cell transplantation (HSCT) at 1.5, 0.9, and 0.6 years of age, respectively. After ERT and/or HSCT, IDS enzyme activity and the quantity of urinary GAGs significantly improved in all of these patients compared with the baseline data. CONCLUSIONS: Because of the progressive nature of MPS II, early diagnosis via a newborn screening program and timely initiation of ERT and/or HSCT before the occurrence of irreversible organ damage may lead to better clinical outcomes. The findings of the current study could serve as baseline data for the analysis of the long-term effects of ERT and HSCT in these patients.
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PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a "pseudokinase", contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a "pseudokinase", has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2-/- mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.
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Objective: In this study, we aim to establish a non-invasive tool to predict epidermal growth factor receptor (EGFR) mutation status and subtypes based on radiomic features of computed tomography (CT). Methods: A total of 233 lung adenocarcinoma patients were investigated and randomly divided into the training and test cohorts. In this study, 2300 radiomic features were extracted from original and filtered (Exponential, Laplacian of Gaussian, Logarithm, Gabor, Wavelet) CT images. The radiomic features were divided into four categories, including histogram, volumetric, morphologic, and texture features. An RF-BFE algorithm was developed to select the features for building the prediction models. Clinicopathological features (including age, gender, smoking status, TNM staging, maximum diameter, location, and growth pattern) were combined to establish an integrated model with radiomic features. ROC curve and AUC quantified the effectiveness of the predictor of EGFR mutation status and subtypes. Results: A set of 10 features were selected to predict EGFR mutation status between EGFR mutant and wild type, while 9 selected features were used to predict mutation subtypes between exon 19 deletion and exon 21 L858R mutation. To predict the EGFR mutation status, the AUC of the training cohort was 0.778 and the AUC of the test cohort was 0.765. To predict the EGFR mutation subtypes, the AUC of training cohort was 0.725 and the AUC of test cohort was 0.657. The integrated model showed the most optimal predictive performance with EGFR mutation status (AUC = 0.870 and 0.759) and subtypes (AUC = 0.797 and 0.554) in the training and test cohorts. Conclusion: CT-based radiomic features can extract information on tumor heterogeneity in lung adenocarcinoma. In addition, we have established a radiomic model and an integrated model to non-invasively predict the EGFR mutation status and subtypes of lung adenocarcinoma, which is conducive to saving clinical costs and guiding targeted therapy.
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Generally, the lower the temperature and/or the longer the duration of low temperature, the more serious chilling injury (CI) symptom appears in fruit. However, our previous study showed that the higher storage temperature (6°C) resulted in a more serious CI in papaya fruit compared to that stored at 1°C, which could be viewed as an abnormal CI behavior. This study investigated the antioxidant responses that existed in abnormal CI behavior of papaya fruit. Compared to 6°C, antioxidant enzyme activities of papaya fruit which was stored at 1°C were maintained at a higher level while the circulatory metabolism of the ascorbate-glutathione cycle (AsA-GSH) was more vigorous in papaya fruit, as indicated by higher superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), and monodehydroascorbate reductase (MDHAR) activities and higher AsA and GSH levels, which could reduce the superoxide anion (·O2 - ) production rate and the hydrogen peroxide (H2 O2 ) content. Suppressed reactive oxygen species (ROS) generation in papaya fruit at 1°C resulted in reduced membrane permeability and malondialdehyde (MDA) accumulation when compared to that at 6°C, thus the development of CI was restricted during storage at 1°C. This study deepened the understanding of differential antioxidant responses during cold storage at 1°C and 6°C in papaya fruit and provided a theoretical basis for further study on the mechanism of the abnormal CI behavior in papaya fruit. PRACTICAL APPLICATIONS: Low-temperature storage is one of the most effective methods to preserve fruit and vegetable products. While, inappropriate low temperature could induce CI, and the damage caused by CI is often more serious than estimated. Therefore, it is necessary to study the physiological and biochemical characteristics of different postharvest fruits and vegetables to prolong storage period, improve storage quality and reduce the loss of products. This study analyzed the antioxidant reaction in abnormal CI behavior of papaya, which could contribute to the further study on the mechanism of CI in papaya fruit and provide theoretical basis for the development of preservation technology of papaya fruit.
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Antioxidantes , Carica , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Carica/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Peróxido de Hidrogênio , Malondialdeído/metabolismo , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo , Superóxidos , VerdurasRESUMO
RRP12 (ribosomal RNA processing 12 homolog) is a nucleolar protein involved in the maturation and transport of eukaryotic ribosomal subunits and is a type of RNA binding protein. In recent years, considerable research has indicated that RRP12 is associated with the occurrence and development of multiple cancers. However, there is no research on RRP12 in hepatocellular carcinoma. Herein, we aimed to explore the role and significance of RRP12 in hepatocellular carcinoma.We used the TIMER and GEPIA databases to perform pan-cancer analyses of RRP12. The impact of RRP12 on the prognosis was analyzed through the GEPIA database. The relationship between RRP12 and immune cell infiltration was investigated by TIMER and GEPIA databases. Moreover, the expression of RRP12 in various liver cancer cells was evaluated by Western Blot to determine the cell line for the next experiment. Scratch test, Transwell test, and Edu tests were applied to validate the effects of RRP12 on the function of liver cancer cells. And the data were statistically analyzed.Pan-cancer analysis found that RPP12 was significantly upregulated in many cancers. Moreover, the prognostic analysis revealed that the difference in the expression of RRP12 has statistical significance for the overall survival rate and disease-free survival rate of liver cancer patients. In order to analyze the correlation between the expression level of RRP12 and clinical parameters, it was found that there was a significant negative correlation with tumor stage, tumor grade and tumor size. Univariate and multivariate analysis showed that RRP12 could be used as an independent prognostic factor for patients with hepatocellular carcinoma. Cellular experiments have proved that knocking down RRP12 can inhibit the proliferation, invasion, and metastasis of liver cancer cells.Therefore, RRP12 significantly affects the occurrence and development of HCC. Hence, RRP12 can become a potential target and prognostic biomarker for the treatment of hepatocellular carcinoma.
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The present study investigated the mechanism of components in stasis-resolving and collateral-dredging Chinese herbal medicines, including scutellarin(Scu), paeonol(Pae), and hydroxy safflower yellow A(HSYA), in the treatment of psoriasis by regulating angiogenesis and inflammation. The human umbilical vein endothelial cells(HUVECs) cultured in vitro were divided into a normal group, a model group, a VEGFR tyrosine kinase inhibitor â ¡(VRI) group, and Scu, Pae, and HSYA groups with low, me-dium, and high doses. Cell viability was detected by the CCK-8 assay. Cell migration was detected by wound healing assay. Tube formation assay was used to measure the tube formation ability. Western blot was used to detect the protein expression of the VEGFR2/Akt/ERK1/2 signaling pathway. The secretion levels of inflammatory cytokines IFN-γ, IL-1ß, IL-6, and TNF-α were detected by ELISA. The results showed that compared with the model group, all the Scu, Pae, and HSYA groups could reduce cell viability, inhibit cell migration and tube formation(P<0.05, P<0.01), and down-regulated the protein expression of VEGFR2, p-VEGFR2, Akt, p-Akt, ERK1/2, and p-ERK1/2. Scu and Pae could down-regulate VEGFR2 expression(P<0.05, P<0.01), while other groups only showed a downward trend. Scu and Pae significantly reduced IFN-γ and IL-6 levels(P<0.01), and HSYA significantly reduced the levels of IFN-γ, IL-1ß, and IL-6(P<0.01). Scu, Pae, and HSYA had no significant effect on TNF-α. The results suggested that Scu, Pae, and HSYA may exert a therapeutic role in psoriasis-related angiogenesis and inflammation by inhibiting VEGFR2/Akt/ERK1/2 signaling pathway and inhibiting the secretion of IFN-γ, IL-1ß, and IL-6.
Assuntos
Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/farmacologia , China , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Differential diagnosis between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains a clinical challenge. OBJECTIVE: The aim of the study is to assess the efficacy of the serum and pleural fluid (PF) miRNA panels in distinguishing MPE from BPE. METHODS: Fourteen candidate miRNAs which were shown aberrant expression in lung cancer based on previous studies were tested by quantitative real-time PCR (qRT-PCR) in 20 MPE patients and 20 BPE patients. Significantly aberrantly expressed miRNAs were further assessed by qRT-PCR in all patients enrolled in this study. A receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to evaluated the diagnostic performance of the miRNAs. RESULTS: miR-21, miR-29c and miR-182 were found to be significantly aberrantly expressed in the serum and PF of MPE patients. The AUCs for the combination of miR-21, miR-29c and miR-182 in serum and PF were 0.832 and 0.89 respectively in distinguishing MPE from infection-associated PE including tuberculous pleurisy and parapneumonia PE, and 0.866 and 0.919 respectively for differentiating MPE from heart failure-associated PE, which were superior to AUC of each individual miRNAs. CONCLUSIONS: miR-21, miR-29c and miR-182 in serum and PF could be useful biomarkers for diagnosis of MPE.
Assuntos
MicroRNAs , Derrame Pleural Maligno , Derrame Pleural , Biomarcadores Tumorais , Diagnóstico Diferencial , Humanos , MicroRNAs/genética , Derrame Pleural/diagnóstico , Derrame Pleural/genética , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/metabolismoRESUMO
The composition of the rhizospheric and endophytic bacteria Phragmites australis in spring and summer around the Qiananling iron tailings reservoir in the Huairou District of Beijing was studied using Illumina high-throughput sequencing technology. Sequencing identified 40 phyla, and Proteobateria and Actinobacteria were the dominant phyla in all samples, accounting for more than 80% of the sequences in all samples. At the genus level, Pseudoarthrobacter was dominant. α-diversity analysis showed that species richness(Sobs, Chao) and species diversity indexes(Shannon, PD) of the rhizosphere soil microorganisms were significantly higher than those of endophytes. The maximum and minimum differences of the Sobs, Chao, Shannon, PD indexes were 1336, 1582.24, 6.48, and 81.18, respectively. ß-diversity analysis indicated that there were significant differences in the community compositions of rhizosphere soil microorganisms and root endophytes, while now notable differences were observed between samples in different seasons. In addition, the dominant strains in each sample(such as Pseudomonas, Arthrobacter, and Streptomyces) were highly resistant to heavy metals. Among the 774 genera, a total of 250 genera coexisted in four types of samples, indicating that the microbial community composition of different samples had some degree of similarity. Correlation analysis between soil physical and chemical properties showed that Ni, Fe, available phosphorus, effective sulphur, and organic matter were significantly related to the microbial communities. Through the prediction of COG function, it was found that the microbial metabolic functions(i.e., energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, inorganic ion transport, and metabolism) were abundant.