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BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) has been widely studied to modulate the immune response. Current stimulating strategies are invasive or imprecise. Noninvasive low-intensity pulsed ultrasound (LIPUS) has become increasingly appreciated for targeted neuronal modulation. However, its mechanisms and physiological role on myocarditis remain poorly defined. METHODS: The mouse model of experimental autoimmune myocarditis was established. Low-intensity pulsed ultrasound was targeted at the spleen to stimulate the spleen nerve. Under different ultrasound parameters, histological tests and molecular biology were performed to observe inflammatory lesions and changes in immune cell subsets in the spleen and heart. In addition, we evaluated the dependence of the spleen nerve and cholinergic anti-inflammatory pathway of low-intensity pulsed ultrasound in treating autoimmune myocarditis in mice through different control groups. RESULTS: The echocardiography and flow cytometry of splenic or heart infiltrating immune cells revealed that splenic ultrasound could alleviate the immune response, regulate the proportion and function of CD4+ Treg and macrophages by activating cholinergic anti-inflammatory pathway, and finally reduce heart inflammatory injury and improve cardiac remodeling, which is as effective as an acetylcholine receptor agonists GTS-21. Transcriptome sequencing showed significant differential expressed genes due to ultrasound modulation. CONCLUSIONS: It is worth noting that the ultrasound therapeutic efficacy depends greatly on acoustic pressure and exposure duration, and the effective targeting organ was the spleen but not the heart. This study provides novel insight into the therapeutic potentials of LIPUS, which are essential for its future application.
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Miocardite , Animais , Camundongos , Miocardite/terapia , Miocardite/patologia , Baço/patologia , Ultrassonografia , Modelos Animais de DoençasRESUMO
BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is finite and they usually bear specific repertoires of bioactive molecules to perform manifold cell-cell communication, but not one particular therapeutic function as expected, their practical application is still limited. Strategies are needed to increase the production of EVs and enhance their therapeutic function. Recent studies have suggested that low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive method to increase the secretion of EVs and promote their anti-inflammatory effects. However, the effect of LIPUS stimulation of BMSCs on EVs derived from the cells remains unclear. The objective of this study was to investigate whether LIPUS stimulation on BMSCs could increase the secretion of EVs and enhance their anti-inflammatory effects. METHODS: BMSCs were exposed to LIPUS (300 mW/cm2) for 15 min and EVs were isolated by ultracentrifugation. Anti-inflammatory effects of EVs were investigated on RAW264.7 cells in vitro and in the allogeneic skin transplantation model. Small RNA-seq was utilized to identify components difference in EVs with/without LIPUS irradiation. RESULTS: In this study, we found that LIPUS stimulation could lead to a 3.66-fold increase in the EVs release from BMSCs. Moreover, both in vitro and in vivo experimental results suggested that EVs secreted from LIPUS-treated BMSCs (LIPUS-EVs) possessed stronger anti-inflammatory function than EVs secreted from BMSCs without LIPUS stimulation (C-EVs). RNA-seq analysis revealed that miR-328-5p and miR-487b-3p were significantly up-regulated in LIPUS-EVs compare with C-EVs. The suppression of MAPK signaling pathway by these two up-regulated miRNAs could be the potential mechanism of strengthened anti-inflammatory effects of LIPUS-EVs. CONCLUSION: LIPUS stimulation on BMSCs could significantly increase the secretion of EVs. Moreover, EVs generated from LIPUS-treated BMSCs possessed much stronger anti-inflammatory function than C-EVs. Therefore, LIPUS could be a promising non-invasive strategy to promote the production of EVs from BMSCs and augment their anti-inflammatory effects.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais , MicroRNAs/metabolismo , Vesículas Extracelulares/metabolismo , Ondas UltrassônicasRESUMO
BACKGROUND: Early identification of axillary lymph node metastasis (ALNM) in breast cancer (BC) is still a clinical difficulty. There is still no good method to replace sentinel lymph node biopsy (SLNB). The purpose of our study was to develop and validate a nomogram to predict the probability of ALNM preoperatively based on ultrasonography (US) and clinicopathological features of primary tumors. METHODS: From September 2019 to April 2022, the preoperative US) and clinicopathological data of 1076 T1-T2 BC patients underwent surgical treatment were collected. Patients were divided into a training set (875 patients from September 2019 to October 2021) and a validation set (201 patients from November 2021 to April 2022). Patients were divided into positive and negative axillary lymph node (ALN) group according pathology of axillary surgery. Compared the US and clinicopathological features between the two groups. The risk factors for ALNM were determined using multivariate logistic regression analysis, and a nomogram was constructed. AUC and calibration were used to assess its performance. RESULTS: By univariate and multivariate logistic regression analysis, age (p = 0.009), histologic grades (p = 0.000), molecular subtypes (p = 0.000), tumor location (p = 0.000), maximum diameter (p = 0.000), spiculated margin (p = 0.000) and distance from the skin (p = 0.000) were independent risk factors of ALNM. Then a nomogram was developed. The model was good discriminating with an AUC of 0.705 and 0.745 for the training and validation set, respectively. And the calibration curves demonstrated high agreement. However, in further predicting a heavy nodal disease burden (> 2 nodes), none of the variables were significant. CONCLUSION: This nomogram based on the US and clinicopathological data can predict the presence of ALNM good in T1-T2 BC patients. But it cannot effectively predict a heavy nodal disease burden (> 2 nodes).
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Neoplasias da Mama , Humanos , Feminino , Metástase Linfática/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Axila/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Biópsia de Linfonodo Sentinela , Nomogramas , Ultrassonografia , Estudos RetrospectivosRESUMO
Potential sources of groundwater pollution in Tongchuan City, China, were qualitatively identified based on 14 key water quality indicators of 59 groundwater samples, and the contribution of each source to groundwater quality was quantitatively evaluated. Groundwater pollution sources were analyzed using PMF and PCA-APCS-MLR models, and their applicability in groundwater pollution assessment in Tongchuan City was tested. Results indicate that both models identified four sources of groundwater contamination. Natural evolution was the main cause of groundwater pollution in the study area, followed by the coal industry, agriculture, and urbanization. Although the spatial distribution of pollution sources in the two models differed, the urbanized area to the east of the study area was more severely affected by sewage discharge, the west was more obviously affected by the coal industry, and the north was mainly polluted by agriculture. Both of the fitting results of the two models are good, but R2 values obtained by the PMF model (0.4440-0.9991) were generally higher than those obtained by the PCA-APCS-MLR model (0.5180-0.9530), indicating that PMF model results were more accurate than the PCA-APCS-MLR model.
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Água Subterrânea , Poluentes Químicos da Água , Agricultura , China , Cidades , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Qualidade da ÁguaRESUMO
The tumor suppressor gene, AT Rich Interactive Domain 1A (ARID1A) mutation has been reported in a variety of cancers, especially the endometrium-related gynecological cancers, including the ovarian clear cell carcinoma, ovarian endometrioid carcinoma, and uterine endometrioid carcinoma. However, the prognostic value of ARID1A in endometrium-related gynecological cancers is still inconclusive. Therefore, we performed this meta-analysis to evaluate the clinical significance of ARID1A in endometrium-related gynecological cancers. By systematically searching all the relevant studies from Pubmed, Cochrane Library, and Web of Science up to September 2016, 11 studies with 1,432 patients were included. All the study characteristics and the prognostic data were extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using the fixed-effect or random-effect model. Our results indicated that negative ARID1A expression predicted shorter Progression free survival (PFS, HR, 1.84; 95%CI, 1.32-2.57, P = 0.000) of patients with endometrium related gynecological cancers, especially the patiently with OCCC and the patients in Japan. Besides, a marginal trend towards the same direction was found in the Overall analysis (OS, HR, 1.34; 95%CI, 0.93-1.93, P = 0.112). Furthermore, the significant correlation was achieved between the negative ARID1A expression and the FIGO stage of endometrium-related gynecological cancers, but not the other characteristics. J. Cell. Biochem. 118: 4517-4525, 2017. © 2017 Wiley Periodicals, Inc.
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Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Neoplasias do Endométrio , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Ovarianas , Fatores de Transcrição/metabolismo , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Proteínas de Ligação a DNA , Intervalo Livre de Doença , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Taxa de SobrevidaRESUMO
BACKGROUND/AIMS: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. METHODS: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. RESULTS: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. CONCLUSION: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.
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Carcinógenos Ambientais/efeitos adversos , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Triazóis/efeitos adversos , Oxirredutases do Álcool/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/genética , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologiaRESUMO
Sonodynamic therapy is an emerging noninvasive tumor treatment method that utilizes ultrasound to stimulate sonosensitizers to produce a large amount of reactive oxygen species, inducing tumor cell death. Though sonodynamic therapy has very promising prospects in cancer treatment, the application of early organic sonosensitizers has been limited in efficacy due to the high blood clearance-rate, poor water solubility, and low stability. Inorganic sonosensitizers have thus been developed, among which piezoelectric semiconductor materials have received increasing attention in sonodynamic therapy due to their piezoelectric properties and strong stability. In this review, we summarized the designs, principles, modification strategies, and applications of several commonly used piezoelectric materials in sonodynamic therapy and prospected the future clinical applications for piezoelectric semiconductor materials in sonodynamic therapy.
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Nanoestruturas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Nanoestruturas/uso terapêuticoRESUMO
T cells serve a pivotal role in the rejection of transplants, both by directly attacking the graft and by recruiting other immune cells, which intensifies the rejection process. Therefore, monitoring T cells becomes crucial for early detection of transplant rejection, while targeted drug delivery specifically to T cells can significantly enhance the effectiveness of rejection therapy. However, regulating the activity of T cells within transplanted organs is challenging, and the prolonged use of immunosuppressive drugs is associated with notable side effects and complications. Functionalized nanoparticles offer a potential solution by targeting T cells within transplants or lymph nodes, thereby reducing the off-target effects and improving the long-term survival of the graft. In this review, we will provide an overview of recent advancements in T cell-targeted imaging molecular probes for diagnosing transplant rejection and the progress of T cell-regulating nanomedicines for treating transplant rejection. Additionally, we will discuss future directions and the challenges in clinical translation.
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Tacrolimus (FK506) is an effective therapeutic for transplant rejection in clinical practice, primarily inhibiting rejection by suppressing the activation and proliferation of allogeneic T cells in the lymph nodes (LNs). However, conventional administration methods face challenges in directly delivering free FK506 to the LNs. In this study, we introduce a novel LN-targeted delivery system based on mesoporous silica nanoparticles (MSNs-FK506-MECA79). These particles were designed to selectively target high endothelial venules in LNs; this was achieved through surface modification with MECA79 antibodies. Their mean size and zeta potential were 201.18 ± 5.98 nm and - 16.12 ± 0.36 mV, respectively. Our findings showed that MSNs-FK506-MECA79 could accumulate in LNs and increase the local concentration of FK506 from 28.02 ± 7.71 ng/g to 123.81 ± 76.76 ng/g compared with the free FK506 treatment group. Subsequently, the therapeutic efficacy of MSNs-FK506-MECA79 was evaluated in a skin transplantation model. The treatment with MSNs-FK506-MECA79 could lead to a decrease in the infiltration of T cells in the grafts, a reduction in the grade of rejection, and a significant prolongation of survival. Consequently, this study presents a promising strategy for the active LN-targeted delivery of FK506 and improving the immunotherapeutic effects on transplant rejection.
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Rejeição de Enxerto , Imunossupressores , Linfonodos , Nanopartículas , Dióxido de Silício , Tacrolimo , Tacrolimo/administração & dosagem , Tacrolimo/química , Dióxido de Silício/química , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Animais , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Imunossupressores/administração & dosagem , Imunossupressores/química , Imunossupressores/farmacologia , Porosidade , Camundongos Endogâmicos BALB C , Transplante de Pele/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/químicaRESUMO
Galectin-3 (Gal-3) participates in myocardial fibrosis (MF) in a variety of ways. Inhibiting the expression of Gal-3 can effectively interfere with MF. This study aimed to explore the value of Gal-3 short hairpin RNA (shRNA) transfection mediated by ultrasound-targeted microbubble destruction (UTMD) in anti-myocardial fibrosis and its mechanism. A rat model of myocardial infarction (MI) was established and randomly divided into control and Gal-3 shRNA/cationic microbubbles + ultrasound (Gal-3 shRNA/CMBs + US) groups. Echocardiography measured the left ventricular ejection fraction (LVEF) weekly, and the heart was harvested to analyze fibrosis, Gal-3, and collagen expression. LVEF in the Gal-3 shRNA/CMB + US group was improved compared with the control group. On day 21, the myocardial Gal-3 expression decreased in the Gal-3 shRNA/CMBs + US group. Furthermore, the proportion of the myocardial fibrosis area in the Gal-3 shRNA/CMBs + US group was 6.9 ± 0.41% lower than in the control group. After inhibition of Gal-3, there was a downregulation in collagen production (collagen I and III), and the ratio of Col I/Col III decreased. In conclusion, UTMD-mediated Gal-3 shRNA transfection can effectively silence the expression of Gal-3 in myocardial tissue, reduce myocardial fibrosis, and protect the cardiac ejection function.
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Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood cell membrane and loaded with doxorubicin (DOX) (F-MSN-DOX@RBC), for RM-1 tumor sonodynamic therapy. Their mean size and zeta potentials were 232 ± 78.8 nm and -35.57 ± 0.74 mV, respectively. The F-MSN-DOX@RBC accumulation in a tumor was significantly higher than in the control group, and the spleen uptake of F-MSN-DOX@RBC was significantly reduced in comparison to that of the F-MSN-DOX group. Moreover, the cavitation caused by a single dose of F-MSN-DOX@RBC combined with multiple ultrasounds provided continuous sonodynamic therapy. The tumor inhibition rates in the experimental group were 71.5 8 ± 9.54%, which is significantly better than the control group. DHE and CD31 fluorescence staining was used to assess the reactive oxygen species (ROS) generated and the broken tumor vascular system induced by ultrasound. Finally, we can conclude that the combination of anti-vascular therapy, sonodynamic therapy by ROS, and chemotherapy promoted tumor treatment efficacy. The use of red blood cell membrane-modified superhydrophobic silica nanoparticles is a promising strategy in designing ultrasound-responsive nanoparticles to promote drug-release.
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Long noncoding RNA (lncRNA) IDH1 antisense RNA 1 ( IDH1-AS1) is involved in the progression of multiple cancers, but its role in epithelial ovarian cancer (EOC) is unknown. Therefore, we investigated the expression levels of IDH1-AS1 in EOC cells and normal ovarian epithelial cells by quantitative real-time PCR (qPCR). We first evaluated the effects of IDH1-AS1 on the proliferation, migration, and invasion of EOC cells through cell counting kit-8, colony formation, EdU, transwell, wound-healing, and xenograft assays. We then explored the downstream targets of IDH1-AS1 and verified the results by a dual-luciferase reporter, qPCR, rescue experiments, and Western blotting. We found that the expression levels of IDH1-AS1 were lower in EOC cells than in normal ovarian epithelial cells. High IDH1-AS1 expression of EOC patients from the Gene Expression Profiling Interactive Analysis database indicated a favorable prognosis, because IDH1-AS1 inhibited cell proliferation and xenograft tumor growth of EOC. IDH1-AS1 sponged miR-518c-5p whose overexpression promoted EOC cell proliferation. The miR-518c-5p mimic also reversed the proliferation-inhibiting effect induced by IDH1-AS1 overexpression. Furthermore, we found that RNA binding motif protein 47 (RBM47) was the downstream target of miR-518c-5p, that upregulation of RBM47 inhibited EOC cell proliferation, and that RBM47 overexpressing plasmid counteracted the proliferation-promoting effect caused by the IDH1-AS1 knockdown. Taken together, IDH1-AS1 may suppress EOC cell proliferation and tumor growth via the miR-518c-5p/RBM47 axis.
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Water resources are important in large basins which are important places for human habitation and industrial and agricultural development. The background of editing this thematic issue was introduced and the general water resources situation and water quality status in four major large river basins in the Asian and African continents were briefly summarized to give readers general pictures of water resources development and management in these basins, and these large river basins are the Yellow River Basin, the Yangtze River Basin, the Indus Basin, and the Nile Basin. The thematic issue papers were classified into four clustered topical categories, and the main points of the papers in this thematic issue were summarized. Finally, the perspectives of future sustainable water resources development and management in large river basins were proposed.
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Real-time monitoring of post-transplant immune response is critical to prolong the survival of grafts. The current gold standard for assessing the immune response to graft is biopsy. However, such a method is invasive and prone to false negative results due to limited tissue size available and the heterogeneity of the rejection site. Herein, we report biomimetic glucan particles with aggregation-induced emission (AIE) characteristics (HBTTPEP/GPs) for real-time noninvasive monitoring of post-transplant immune response. We have found that the positively charged near-infrared AIEgens can effectively aggregate in the confined space of glucan particles (GPs), thereby turning on the fluorescence emission. HBTTPEP/GPs can track macrophages for 7 days without hampering the bioactivity. Oral administration of HBTTPEP/GPs can specially target macrophages by mimicking yeast, which then migrate to the transplant rejection site. The fluorescence emitted from HBTTPEP/GPs correlated well with the infiltration of macrophages and the degree of allograft rejection. Furthermore, a single oral HBTTPEP/GPs dose can dynamically evaluate the therapeutic response to immunosuppressive therapy. Consequently, the biomimetic AIE-active glucan particles can be developed as a promising probe for immune-monitoring in solid organ transplantation.
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Biomimética , Glucanos , Rejeição de Enxerto , Transplante Homólogo , ImunidadeRESUMO
As an oncogenic virus, HPV16 can lead to the dysfunction of cervical epithelial cells and contribute to the progression of cervical cancer. Components from the cervical-vaginal fluid (CVF) could be used as the basis for cervical cancer screening. Exosomes are widely present in various body fluids and participate in intercellular communication via its cargos of proteins, mRNAs, and miRNAs. This study was conducted to explore the changes of miRNAs in exosomes isolated form the cervical-vaginal fluid during HPV16 infection and to predict the potential effects of exosomal miRNAs on the development of cervical cancer. CVF was collected from volunteers with or without HPV16 infection. The exosomes in CVF were identified by electron microscopy. Microarray analysis was subjected to find the differentially expressed miRNAs in CVF exosomes. To confirm the results, 16 miRNAs were randomly selected to go through real-time quantitative polymerase chain reaction. In addition, GO and pathway analyses were conducted to reveal potential functions of differentially expressed miRNAs. A total of 2548 conserved miRNAs were identified in the cervical-vaginal fluid-derived exosomes. In response to HPV16 infection, 45 miRNAs are significantly upregulated and 55 miRNAs are significantly downregulated (P < 0.05). The GO and KEGG pathway analyses revealed that these differentially expressed miRNAs are tightly associated with cervical cancer tumorigenesis, through interaction with the Notch signaling pathway, TNF signaling pathway, and TGF-ß signaling pathway. These results suggest that exosomal miRNAs in CVF are differentially expressed in HPV16 infection patients and HPV16-free volunteers. It provided a novel insight to understand the underlying mechanism of HPV16 infection in regulating cervical cancer progression.
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Colo do Útero/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Infecções por Papillomavirus/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/metabolismo , Vagina/metabolismo , Adulto , Feminino , Perfilação da Expressão Gênica , Papillomavirus Humano 16/metabolismo , Humanos , Análise em Microsséries , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/etiologia , Adulto JovemRESUMO
Subsequently to the publication of this article, the authors have noted that the second and third named authors on the paper, Lihua Zeng and Jiahui Chu, were not accredited as being joint first authors on this paper, and equal contributors with Lei Huang. The elimination of the necessary asterisks occurred during the prepress stages. Therefore, the correct author affliations for this article should have appeared as follows: Lei Huang1,2*, Lihua Zeng3*, Jiahui Chu1*, Pengfei Xu3, Mingming Lv3, Juan Xu3, Juan Wen3, Wenqu Li3, Luyu Wang4, Xiaowei Wu5, Ziyi Fu3, Hui Xie1 and Shui Wang1. 1Department of Breast Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029; 2Department of General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008; 3Nanjing Maternity and Child Health Medical Institute, Affiliated Nanjing Maternal and Child Health Hospital, Nanjing Medical University, Nanjing, Jiangsu 210004; 4Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004; 5Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China. *Contributed equally. The Editor apologizes to the authors for this oversight on our part, and for the inconvenience caused. [the original article was published in Molecular Medicine Reports 18: 243253, 2018; DOI: 10.3892/mmr.2018.8942].
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Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in females worldwide. Chemoresistance has been a major reason for the drug therapy failure. The present study performed a microarray analysis between MCF7 and MCF7/adriamycin (ADR) cells, and intended to identify long noncoding (lnc)RNA expression character in drug resistant breast cancer cells. MCF7/ADR cells were induced from MCF7 cells via pulseselection with doxorubicin for 4 weeks, and the resistance to doxorubicin of ADR cells was confirmed by MTT assay. Microarray analysis was performed between MCF7 and MCF7/ADR cells. Total RNA was extracted from the two cell lines respectively and was transcribed into cDNA. The results of the microarray were verified by reverse transcriptionquantitative polymerase chain reaction (RTqPCR). Gene Ontology (GO) and pathways analysis were conducted to enrich the dysregulated lncRNAs presented in the microarray results. Compared to the MCF7 cells, 8,892 lncRNAs were differentially expressed in MCF/ADR cells (absolute foldchange >2.0). A total of 32 lncRNAs were selected for RTqPCR by foldchange filtering, standard Student's ttest, and multiple hypothesis testing. Among the dysregulated lncRNAs, AX747207 was prominent because its associated gene RUNX3 was previously reported to be relative to malignant tumor chemoresistance. GO analysis results also indicated some biological processes and molecular functions linked to chemoresistance. The pathway enrichment results provided some potential pathways associated with chemoresistance. In the present study, the authors intended to identify lncRNA expression character in drug resistant cell line MCF7/ADR, corresponding to the parental MCF7 cell line. In addition, the study identified the lncRNA AX747207, and its potential targeted gene RUNX3, may be related to chemoresistance in breast cancer. These results may new insights into exploring the mechanisms of chemoresistance in breast cancer.
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Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , RNA Neoplásico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Células MCF-7 , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genéticaRESUMO
Endometriosis is a benign disease, but has invasion and metastasis characteristics similar to malignant tumors. Clinically, it is a difficult problem of gynecological clinical treatment for its high recurrence rate. It has been confirmed that miR-363 was downregulated in endometriosis tissues and miR-363 overexpression inhibited the invasion ability of endometrial stromal cells (ESCs). In order to explore the potential mechanism of miR-363-reduced ESC migration and invasion progression, we sought to demonstrate the targeted mRNA expression levels of miR-363 through microarray, and performed cluster analysis to identify potential functions of these targeted genes in ESCs. The wound migration assay showed that there was an observable trend of cell migration potential decrease after transfection with hsa-miR-363. The qRT-PCR result showed that compared to miR-363 negative control cell group, miR-363 was upregulated 3,264.58-fold after miR-363 lentiviral transfection in miR-363 mimics group. The microarray data showed that compared to ESCs miR-363 negative control cell group, 249 genes were upregulated in ESCs miR-363 mimics cells group, and 139 genes were downregulated. Gene Ontology analysis and the pathway analysis data demonstrated that these target genes are mainly involved in cell migration, cell adhesion and invasion, proliferation, apoptosis, alteration of endometrial cells and some related signaling pathways. Our study explored the gene expression pattern after miR-363 overexpression, which could expand the insights into the miR-363 function and molecular mechanisms in endometriosis.