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Starvation therapy is an innovative approach in cancer treatment aimed at depriving cancer cells of necessary resources by impeding tumor angiogenesis or blocking the energy supply. In addition to the commonly observed anaerobic glycolysis energy supply mode, adipocyte-rich tumor tissue triggers the fatty acid energy supply pathway, which fuels the proliferation and metastasis of cancer cells. To completely disrupt these dual-energy-supply pathways, we developed an exceptional nanoreactor. This nanoreactor consisted of yolk-shell mesoporous organosilica nanoparticles (YSMONs) loaded with a fatty acid transport inhibitor (Dox), conjugated with a luminal breast-cancer-specific targeting aptamer, and integrated with a glucose oxidation catalyst (GOx). Upon reaching cancer cells with the assistance of the aptamer, the nanoreactor underwent a structural collapse of the shell triggered by the high concentration of glutathione within cancer cells. This collapse led to the release of GOx and Dox, achieving targeted delivery and exhibiting significant efficacy in starving therapy. Additionally, the byproducts of glucose metabolism, gluconic acid and H2O2, enhanced the acidity and reactive oxygen species levels of the intracellular microenvironment, inducing oxidative damage to cancer cells. Simultaneously, released Dox acted as a potent broad-spectrum anticancer drug, inhibiting the activity of carnitine palmitoyltransferase 1A and exerting marked effects. Combining these effects ensures high anticancer efficiency, and the "dual-starvation" nanoreactor has the potential to establish a novel synergistic therapy paradigm with considerable clinical significance. Furthermore, this approach minimizes damage to normal organs, making it highly valuable in the field of cancer treatment.
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Antineoplásicos , Neoplasias da Mama , Nanopartículas , Neoplasias , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Peróxido de Hidrogênio/química , Antineoplásicos/farmacologia , Glutationa , Ácidos Graxos , Nanopartículas/química , Neoplasias/patologia , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Though single cell RNA sequencing (scRNA-seq) technologies have been well developed, the acquisition of large-scale single cell expression data may still lead to high costs. Single cell expression profile has its inherent sparse properties, which makes it compressible, thus providing opportunities for solutions. Here, by computational simulation as well as experiment of 54 single cells, we propose that expression profiles can be compressed from the dimension of samples by overlapped assigning each cell into plenty of pools. And we prove that expression profiles can be inferred from these pool expression data with overlapped pooling design and compressed sensing strategy. We also show that by combining this approach with plate-based scRNA-seq measurement, it can maintain its superiorities in gene detection sensitivity and individual identity and recover the expression profile with high precision, while saving about half of the library cost. This method can inspire novel conceptions on the measurement, storage or computation improvements for other compressible signals in many biological areas.
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Algoritmos , Simulação por Computador , Perfilação da Expressão Gênica/métodos , Modelos Teóricos , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Animais , Bases de Dados Genéticas/estatística & dados numéricos , Biblioteca Gênica , Humanos , Reprodutibilidade dos TestesRESUMO
Pro-apoptosis in cancer cells has been proposed as a beneficial therapeutic strategy for potentiating the anticancer effects of radiotherapy. TNF-related apoptosis inducing ligand (TRAIL) and Second mitochondria derived activator of caspase (Smac) can induce cell apoptosis. Herein, we designed a conditionally replicating adenoviral co-overexpression vector of TRAIL and Smac regulated by the Egr1 promoter, in which hTERT, E1A-E1B and E1B55K genes were inserted to achieve enhanced tumor targeting characteristics. After breast cancer MDA-MB-231 cells were infected and irradiated, cellular proliferation and colony formation were measured, apoptotic rate was detected by FCM after AnnexinV-FITC/PI staining. To explore the molecular mechanisms of apoptosis, mRNA and protein levels of TRAIL, Smac, Cytochrome c (Cyt c), death receptor 5 (DR5), caspase-8, -9 and -3 were measured by quantitative real-time PCR, ELISA and Western blot, and caspase-3 activity was detected using caspase-3 activity kits. The results showed that TRAIL and/or Smac overexpression enhanced proliferation inhibition and radio-sensitivity through apoptosis. In addition, the combination of IR and overexpression of TRAIL and/or Smac can activate more apoptosis in tumor cells, and the transcriptional levels and protein expressions of Cyt c, DR5, caspase-8, -9 and -3 had similar regularity with apoptotic changes, indicating the molecular mechanisms of TRAIL and Smac involves the mitochondrial pathway. Our findings may have implications for novel radiotherapy plans for breast tumor treatment.
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Proteínas Reguladoras de Apoptose , Apoptose , Caspases , Mitocôndrias , Proteínas Mitocondriais , Radioterapia , Ligante Indutor de Apoptose Relacionado a TNF , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Humanos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismoRESUMO
BACKGROUND: Gastric cancer is one of the most prevalent and deadly malignancies without efficient treatment option. This study aimed to investigate the effect of hydrogen gas on the behavior of gastric cancer cells. METHODS: Gastric cancer cell lines MGC-803 and BGC-823 were treated with or without H2 /O2 gas mixture (66.7%:33.3% v/v). Proliferation and migration were assessed by MTT and scratch wound healing assays respectively. The expression of lncRNA MALAT1, miR-124-3p, and EZH2 was analyzed by real-time quantitative PCR and/or western blot. Tumor growth was estimated using xenograft mouse model. RESULTS: H2 gas significantly inhibited gastric tumor growth in vivo and the proliferation, migration, and lncRNA MALAT1 and EZH2 expression of gastric cancer cells while upregulated miR-124-3p expression. LncRNA MALAT1 overexpression abolished all the aforementioned effects of H2. LncRNA MALAT1 and miR-124-3p reciprocally inhibited the expression of each other. MiR-124-3p mimics abrogated lncRNA MALAT1 promoted EZH2 expression and gastric cancer cell proliferation and migration. CONCLUSIONS: These data demonstrated that H2 might be developed as a therapeutics of gastric cancer and lncRNA MALAT1/miR-124-3p/EZH2 axis could be a target for intervention.
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Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F) is a diterpenoid that is isolated and purified from the Chinese herbal medicine Pteris semipinnata L., and is known to exert antitumour activity in several kinds of malignant cancer cells by leading cancer cells to apoptosis. However, the antitumour effect of 5F in vivo is rarely reported due to the complexity of the physiological environment and limitations of 5F as a small anticancer drug. In the present study, we utilized FITC-doped nanoparticles for the accumulation and delivery of 5F in nasopharyngeal carcinoma CNE2 tumours transplanted in nude mice by the enhanced permeation and retention (EPR) effect. In vivo studies demonstrated that nanoparticles could efficiently deliver 5F in CNE2 transplanted tumours, and the tumour growth was effectively inhibited by the drug-loaded nanoparticles with minimal side effects. The study indicated the benefits of combining well-studied nanoparticles with traditional herbal medicine treatment and establishes a delivery platform for 5F chemotherapy.
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Nanopartículas , Neoplasias Nasofaríngeas , Animais , Diterpenos , Camundongos , Camundongos Nus , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Dióxido de SilícioRESUMO
Recent studies demonstrated that FoxO3 circular RNA (circFoxO3) plays an important regulatory role in tumourigenesis and cardiomyopathy. However, the role of circFoxO3 in neurodegenerative diseases remains unknown. The aim of this study was to examine the possible role of circFoxO3 in neurodegenerative diseases and the underlying mechanisms. To model human neurodegenerative conditions, hippocampus-derived neurons were treated with glutamate. Using molecular and cellular biology approaches, we found that circFoxO3 expression was significantly higher in the glutamate treatment group than that in the control group. Furthermore, silencing of circFoxO3 protected HT22 cells from glutamate-induced oxidative injury through the inhibition of the mitochondrial apoptotic pathway. Collectively, our study demonstrates that endogenous circFoxO3 plays a key role in inducing apoptosis and neuronal cell death and may act as a novel therapeutic target for neurodegenerative diseases.
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Apoptose/efeitos dos fármacos , Ácido Glutâmico/farmacologia , Hipocampo/metabolismo , Mitocôndrias/metabolismo , RNA Circular/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteína Forkhead Box O3/genética , Ácido Glutâmico/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Background and Purpose: Oxidative stress is involved in the development of infections. However, whether oxidative stress indicators can be used as markers of stroke-associated infection (SAI) is still unclear. The purpose of this study was to test the predictive values of superoxide dismutase (SOD) and malondialdehyde (MDA) levels for SAI incidence.Methods: A total of 45 consecutive patients with ischemic stroke who were admitted to our hospital were enrolled. A prospective study was carried out to observe the occurrence of SAI during the first 7 days after stroke. Accordingly, the patients were divided into SAI and non-SAI groups. The relationship between SOD and MDA serum levels and SAI was analyzed.Results: The patients in the SAI group had significantly higher serum SOD levels than those in the non-SAI group (41.638 ± 3.428 U/ml vs. 36.542 ± 9.114 U/ml, p = 0.033). However, there were no significant differences in MDA levels between the SAI and non-SAI group (p > 0.05). The discriminating ability of serum SOD level for SAI was measured using an ROC curve. Serum level of SOD >38.16 U/ml was useful in diagnosing SAI with a sensitivity of 88% and a specificity of 61%. Kaplan-Meier curves showed that the group with serum SOD level >38.16 U/ml had higher rates of SAI incidence (χ2 = 9.688, p = 0.002; log rank test). Furthermore, Cox regression analysis indicated that a serum SOD level >38.16 U/ml was an independent risk factor for SAI (hazard ratio = 5.836; 95% CI, 1.298-26.244; p = 0.021).Conclusions: Acute-phase serum SOD level could be a predictor of SAI.
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Isquemia Encefálica/sangue , Infecções/sangue , Infecções/diagnóstico , Inflamação/sangue , Estresse Oxidativo , Acidente Vascular Cerebral/sangue , Superóxido Dismutase/sangue , Idoso , Biomarcadores/sangue , Isquemia Encefálica/complicações , Feminino , Humanos , Infecções/etiologia , Inflamação/etiologia , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Acidente Vascular Cerebral/complicaçõesRESUMO
Glutathione S-transferase T1 (GSTT1) catalyzes reactions between glutathione and lipophilic compounds with electrophilic centers, leading to neutralization of toxic compounds, xenobiotics, and products of oxidative stress. In the past decade, a number of case-control studies have been carried out to investigate the relationship between the GSTT1 null polymorphism and gastric cancer (GC), but the results have been inconclusive. To investigate this inconsistency, we performed a meta-analysis of 46 studies involving a total of 9012 GC cases and 14,215 controls for null variant of the GSTT1 gene to evaluate the effect of GSTT1 on genetic susceptibility for GC. Potential sources of heterogeneity including ethnicity, source of control, and sample size were also assessed. Overall, significantly increased GC risk was associated with GSTT1 null polymorphism with OR of 1.20 (95% CI, 1.10-1.32; P < 0.05). In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians and Indians, while no significant associations were found among Caucasian, and Middle Eastern and African populations. By pooling data from 19 studies that considered combinations of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for GC (OR = 2.04, 95% CI, 1.49-2.64; P < 0.05) was detected for individuals with dual deletion in both genes compared with positive genotypes. In addition, we found that cigarette smoking and alcohol drinking may modified the association of GSTT1 null genotypes with the risk of GC. In conclusion, this meta-analysis suggests that GSTT1 null polymorphism is associated with elevated GC risk, but these associations vary in different ethnic populations.
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Estudos de Associação Genética , Glutationa Transferase/genética , Homozigoto , Neoplasias Gástricas/genética , Estudos de Casos e Controles , Epistasia Genética , Interação Gene-Ambiente , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Viés de Publicação , Risco , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/etiologiaRESUMO
In several forms of malignant tumors, nuclear enriched abundant transcript 1 (NEAT1), a lncRNA, has been identified to play an important role. NEAT1's regulation patterns in prostate cancer (PCa) are, however, mainly unknown. This study was aimed to evaluate and study the roles and regulatory mechanisms of NEAT1 in PCa. NEAT1, miR-582-5p, and enhancer of zeste homolog 2 (EZH2) expression were detected by qRT-PCR. The PCa cells' invasive, migrative, and proliferative activities in vitro were assessed using transwell migration and invasion, wound-healing, cloning creation, and CCK-8 assays. In the present study, impaired proliferative, migrative, and invasive capacities were observed in the NEAT1-deficient PCa (PC3 and LNCaP) cells. Further mechanistic studies found that NEAT1 performs its function through sponging miR-582-5p. Furthermore, EZH2 was confirmed to be the downstream target gene of miRNA-582-5p. The impaired progression caused by NEAT1 deficiency in PCa cells was significantly restored by the inhibition of miR-582-5p, while these effects were largely abolished by the deletion of EZH2. Finally, the xenograft nude mouse model showed that knocking down the expression of NEAT1 suppressed the growth of PCa. In conclusion, NEAT1 promotes the progression of PCa by controlling the miR-582-5p and miR-582-5p-mediated EZH2. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-023-00612-z.
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OBJECTIVE: Upper urinary tract stones (UUTSs) are among the most common types of urinary stones, and their incidence rate has been increasing annually in recent years, seriously affecting the daily lives of patients. This study aimed to compare the treatment efficacy of one-stage and staged flexible ureteroscopic lithotripsy (FURL) for UUTSs. METHODS: A total of 142 patients with UUTSs admitted to our hospital between December 2019 and March 2023 were selected for retrospective analysis, including 76 patients who received staged FURL (control group) and 66 patients who received one-stage FURL (observation group). The duration of surgery, length of stay, stone clearance rate, incidence of postoperative complications (from postsurgery to discharge), and total hospitalization cost were analyzed in both groups. The visual analog scale (VAS) score and activities of daily living (ADL) score were assessed before surgery (T0), 3 days after surgery (T1), and 7 days after surgery (T2). Patients were followed up for 1 month after surgery, and their quality of life was assessed using the MOS Item Short Form Health Survey (SF-36). RESULTS: There was no difference in the stone clearance rate or incidence of postoperative complications between the two groups (p > 0.05). The operation time, hospitalization time and hospitalization cost in the observation group were 75.58 ± 15.91 min, 4.20 ± 1.24 days and 14312.62 ± 1078.89 yuan, respectively, which were lower than those in the control group (p < 0.05). In addition, the VAS score at T3 was decreased to 1.49 ± 0.70, while the ADL and SF-36 scores were higher in the observation group (p < 0.05). CONCLUSIONS: One-stage FURL shortens the duration of surgery and length of stay, reduces hospitalization costs, and improves the quality of life of patients with UUTSs.
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Cálculos Renais , Cálculos Ureterais , Ureteroscopia , Humanos , Masculino , Feminino , Ureteroscopia/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Cálculos Renais/cirurgia , Cálculos Ureterais/cirurgia , Adulto , Litotripsia/métodos , Ureteroscópios , IdosoRESUMO
Radiation therapy has been a critical and effective treatment for cancer. However, not all cells are destroyed by radiation due to the presence of tumor cell radioresistance. In the current study, we investigated the effect of low-dose radiation (LDR) on the tumor suppressive effect of high-dose radiation (HDR) and its mechanism from the perspective of tumor cell death mode and DNA damage repair, aiming to provide a foundation for improving the efficacy of clinical tumor radiotherapy. We found that LDR pre-irradiation strengthened the HDR-inhibited A549 cell proliferation, HDR-induced apoptosis, and G2 phase cell cycle arrest under co-culture conditions. RNA-sequencing showed that differentially expressed genes after irradiation contained pyroptosis-related genes and DNA damage repair related genes. By detecting pyroptosis-related proteins, we found that LDR could enhance HDR-induced pyroptosis. Furthermore, under co-culture conditions, LDR pre-irradiation enhances the HDR-induced DNA damage and further suppresses the DNA damage-repairing process, which eventually leads to cell death. Lastly, we established a tumor-bearing mouse model and further demonstrated that LDR local pre-irradiation could enhance the cancer suppressive effect of HDR. To summarize, our study proved that LDR pre-irradiation enhances the tumor-killing function of HDR when cancer cells and immune cells were coexisting.
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Radiation-Induced Pulmonary Fibrosis (RIPF) frequently arises as a delayed complication following radiation therapy for thoracic cancers, encompassing lung, breast, and esophageal malignancies. Characterized by a relentless and irreversible accumulation of extracellular matrix (ECM) proteins within the lung parenchyma, RIPF presents a significant clinical challenge. While the modulation of gene expression by transcription factors is a recognized aspect in various pathologies, their specific role in the context of RIPF has been less clear. This study elucidates that ionizing radiation prompts the translocation of the transcription factor GATA3 into the nucleus. This translocation facilitates GATA3's binding to the NRP1 promoter, thereby enhancing the transcription and subsequent translation of NRP1. Further investigations demonstrate that the TGF-ß pathway agonist, SRI-011381, can mitigate the effects of NRP1 knockdown on epithelial-mesenchymal transition (EMT) and ECM deposition, suggesting a pivotal role of the GATA3/NRP1/TGF-ß axis in the pathogenesis of RIPF. In conclusion, our findings not only underscore the critical involvement of GATA3 in RIPF but also highlight the GATA3/NRP1/TGF-ß signaling pathway as a promising target for therapeutic intervention in RIPF management.
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Fibrose Pulmonar , Humanos , Fibrose Pulmonar/induzido quimicamente , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/uso terapêutico , Transdução de Sinais/fisiologia , Pulmão/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Transição Epitelial-Mesenquimal/genéticaRESUMO
Objective: This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. Methods: Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. Results: SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P < 0.05). After SNHG16 silence, KIRC cells showed decreased proliferation, invasion and migration capabilities and increased apoptosis rate; correspondingly, increase in SNHG16 expression achieved opposite results (P < 0.05). Finally, in the rescue experiment, the effects of elevated SNHG16 on KIRC cells were reversed by simultaneous increase in miR-506-3p, and the effects of miR-506-3p were reversed by ETS1. Activation of the RAS/ERK pathway had the same effect as increase in ETS1, which further worsened the malignancy of KIRC. After miR-506-3p increase and ETS1 silence, the RAS/ERK signaling pathway was inhibited (P < 0.05). At last, the rescue experiment (co-transfection) confirmed that the effect of SNHG16 on KIRC cells is achieved via the miR-506-3p/ETS1/RAS/ERK molecular axis. Conclusion: SNHG16 regulates the biological behavior of KIRC cells by targeting the miR-506-3p/ETS1/RAS/ERK molecular axis.
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The genus Gnaphalium, a herb distributed worldwide, comprises approximately 200 species of the Compositae (Asteraceae) family that belongs to the tribe Gnaphalieae. Some species are traditionally used as wild vegetables and in folk medicine. This review focuses on the phytochemical investigations and biological studies of plants from the genus Gnaphalium over the past few decades. More than 125 chemical constituents have been isolated from the genus Gnaphalium, including flavonoids, sesquiterpenes, diterpenes, triterpenes, phytosterols, anthraquinones, caffeoylquinic acid derivatives, and other compounds. The extracts of this genus, as well as compounds isolated from it, have been demonstrated to possess multiple pharmacological activities such as antioxidant, antibacterial and antifungal, anti-complement, antitussive and expectorant, insect antifeedant, cytotoxic, anti-inflammatory, antidiabetic and antihypouricemic properties. The present review compiles the information available on this genus because of its relevance to food and ethnopharmacology and the potential therapeutic uses of these species.
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Gnaphalium/química , Compostos Fitoquímicos/farmacologia , Etnofarmacologia , Gnaphalium/classificação , Medicina Herbária , Medicina Tradicional , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
Shear wave elastography (SWE) of human skeletal muscles allows for measurement of muscle elastic properties in vivo and has important applications in sports medicine and for the diagnosis and treatment of muscle-related diseases. Existing methods of SWE for skeletal muscles rely on the passive constitutive theory and have so far been unable to provide constitutive parameters describing muscle active behavior. In the present paper, we overcome this limitation by proposing a SWE method for quantitative inference of active constitutive parameters of skeletal muscles in vivo. To this end, we investigate the wave motion in a skeletal muscle described by a constitutive model in which muscle active behavior has been defined by an active parameter. An analytical solution relating shear wave velocities to both passive and active material parameters of muscles is derived, based upon which an inverse approach has been developed to evaluate these parameters. To demonstrate the usefulness of the reported method, in vivo experiments were carried out on 10 volunteers to obtain constitutive parameters, particularly those describing active deformation behaviors of living muscles. The results reveal that the active material parameter of skeletal muscles varies with warm-up, fatigue and rest. STATEMENT OF SIGNIFICANCE: Existing shear wave elastography methods are limited to imaging the passive parameters of muscles. This limitation is addressed in the present paper by developing a method to image the active constitutive parameter of living muscles using shear waves. We derived an analytical solution demonstrating the relationship between constitutive parameters of living muscles and shear waves. Relying on the analytical solution, we proposed an inverse method to infer active parameter of skeletal muscles. We performed in vivo experiments to demonstrate the usefulness of the theory and method; the quantitative variation of the active parameter with muscle states such as warm-up, fatigue and rest has been reported for the first time.
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Técnicas de Imagem por Elasticidade , Músculo Esquelético , Humanos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologiaRESUMO
PURPOSE: Recent studies have revealed an increase in the incidence rate of non-alcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC). Furthermore, the association of Sphingosine 1-phosphate receptor 2 (S1PR2) with various types of tumours is identified, and the metabolism of conjugated bile acids (CBAs) performs an essential function in the onset and development of HCC. However, the association of CBA and S1PR2 with NAFLD-HCC is unclear. METHODS: The relationship between the expression of S1PR2 and the prognosis of patients suffering from NAFLD-HCC was investigated by bioinformatics techniques. Subsequently, the relationship between S1PR2 and the biological behaviours of HCC cell lines Huh 7 and HepG2 was explored by conducting molecular biology assays. Additionally, several in vivo animal experiments were carried out for the elucidation of the biological impacts of S1PR2 inhibitors on HCC cells. Finally, We used Glycodeoxycholic acid (GCDA) of CBA to explore the biological effects of CBA on HCC cell and its potential mechanism. RESULTS: High S1PR2 expression was linked to poor prognosis of the NAFLD-HCC patients. According to cellular assay results, S1PR2 expression could affect the proliferation, invasion, migration, and apoptosis of Huh 7 and HepG2 cells, and was closely associated with the G1/G2 phase of the cell cycle. The experiments conducted in the In vivo conditions revealed that the overexpression of S1PR2 accelerated the growth of subcutaneous tumours. In addition, JTE-013, an antagonist of S1PR2, effectively inhibited the migration and proliferation of HCC cells. Furthermore, the bioinformatics analysis highlighted a correlation between S1PR2 and the PI3K/AKT/mTOR pathway. GCDA administration further enhanced the expression levels of p-AKT, p-mTOR, VEGF, SGK1, and PKCα. Moreover, both the presence and absence of GCDA did not reveal any significant change in the levels of S1PR2, p-AKT, p-mTOR, VEGF, SGK1, and PKCα proteins under S1PR2 knockdown, indicating that CBA may regulates the PI3K/AKT/mTOR pathway by mediating S1PR2 expression. CONCLUSION: S1PR2 is a potential prognostic biomarker in NAFLD-HCC. In addition, We used GCDA in CBAs to treat HCC cell and found that the expression of S1PR2 was significantly increased, and the expression of PI3K/AKT/mTOR signalling pathway-related signal molecules was also significantly enhanced, indicating that GCDA may activate PI3K/AKT/mTOR signalling pathway by up-regulating the expression of S1PR2, and finally affect the activity of hepatocellular carcinoma cells. S1PR2 can be a candidate therapeutic target for NAFLD-HCC. Collectively, the findings of this research offer novel perspectives on the prevention and treatment of NAFLD-HCC.
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The clinical and economic burdens of cardiovascular diseases pose a global challenge. Growing evidence suggests an early assessment of arterial stiffness can provide insights into the pathogenesis of cardiovascular diseases. However, it remains difficult to quantitatively characterize local arterial stiffness in vivo. Here we utilize guided axial waves continuously excited and detected by ultrasound to probe local blood pressures and mechanical properties of common carotid arteries simultaneously. In a pilot study of 17 healthy volunteers, we observe a â¼ 20 % variation in the group velocities of the guided axial waves (5.16 ± 0.55 m/s in systole and 4.31 ± 0.49 m/s in diastole) induced by the variation of the blood pressures. A linear relationship between the square of group velocity and blood pressure is revealed by the experiments and finite element analysis, which enables us to measure the waveform of the blood pressures by the group velocities. Furthermore, we propose a wavelet analysis-based method to extract the dispersion relations of the guided axial waves. We then determined the shear modulus by fitting the dispersion relations in diastole with the leaky Lamb wave model. The average shear modulus of all the volunteers is 166.3 ± 32.8 kPa. No gender differences are found. This study shows the group velocity and dispersion relation of the guided axial waves can be utilized to probe blood pressure and arterial stiffness locally in a noninvasive manner and thus promising for early diagnosis of cardiovascular diseases.
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Doenças Cardiovasculares , Técnicas de Imagem por Elasticidade , Rigidez Vascular , Pressão Sanguínea , Técnicas de Imagem por Elasticidade/métodos , Humanos , Projetos Piloto , Rigidez Vascular/fisiologiaRESUMO
Aging and cardiovascular diseases (CVDs) may alter the microstructures of arteries and hence their mechanical properties. Therefore, the measurement of intrinsic artery mechanical properties in vivo can provide valuable information in understanding aging and CVDs and is of clinical significance. The accuracy of advanced ultrasound imaging techniques in measuring the deformation of large arteries under blood pressure is good. However, the assessment of arterial stiffness in vivo remains a challenge. An inverse method to infer the constitutive parameters of arteries in vivo from the blood pressure-arterial radius relationship (P-r curve) is proposed here. The stability analysis reveals that a key constitutive parameter, bθ, which measures the circumferential hardening of an artery, can be reliably identified. An in vivo experiment was performed on the common carotid arteries of 41 healthy volunteers (age: 37 ± 17 y). The value of bθ varies significantly (from 0.55 ± 0.15 for the young group to 0.93 ± 0.29 for the older group, p < 0.01) and is positively correlated with age (r = 0.673, p < 0.01). Furthermore, our theoretical analysis and experimental study have revealed a strong correlation between the clinic-used stiffness index ß and bθ. This study shows that the arterial material parameter bθ can be measured in vivo, which makes it promising as a new biomarker in the diagnosis of CVDs.
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Artérias , Rigidez Vascular , Adulto , Envelhecimento/fisiologia , Artérias/diagnóstico por imagem , Artérias/fisiologia , Pressão Sanguínea , Humanos , Pessoa de Meia-Idade , Ultrassonografia , Adulto JovemRESUMO
Antigen CD133 is a glycoprotein present on the surface of cancer stem cells (CSCs), which is a key molecule to regulate the fate of stem cells and a functional marker of stem cells. Herein, a novel fluorescence "turn-on" nano-aptamer sensor for quantifying CD133 was designed using hybridization between CD133-targeted aptamers and partially complementary paired RNA (ssRNA), which were modified on the surface of quantum dots (QDs) and gold nanoparticles (AuNPs), respectively. Owing to the hybridization of aptamers and ssRNA, the distance between QDs and AuNPs was shortened, which caused fluorescence resonance energy transfer (FRET) between them, and the florescence of QDs was quenched by AuNPs. When CD133 competitively replaced ssRNA and was bound to aptamers, AuNPs-ssRNA could be released, which led to a recovery of fluorescent signals of QDs. The increase in the relative value of fluorescence intensity was investigated to linearly correlate with the CD133 concentration in the range of 0-1.539 µM, and the detection limit was 6.99 nM. In confocal images of A549 cells, the CD133 aptamer sensor was further proved applicable in lung cancer cell samples with specificity, precision, and accuracy. Compared with complicated methods, this study provided a fresh approach to develop a highly sensitive and selective detection sensor for CSC markers.
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OBJECTIVE: Visceral venous aneurysms are very rare, especially in the kidney. The diagnosis of renal venous aneurysms is difficult. If complications such as thrombosis, embolism or rupture, there can be corresponding clinical symptoms. In severe cases, it can lead to the death of the patient. Endoscopic resection of renal venous aneurysms has not been reported in the literature. This paper preliminarily discusses the experience of laparoscopic resection of renal venous aneurysms. METHODS: Recently, a patient with left retroperitoneal space occupying lesion was admitted to our hospital. More than a year ago, the patient was found to have left retroperitoneal space occupying lesion by CT plain scan, accompanied by occasional upper abdominal and precordial discomfort at night. After admission, enhanced CT showed that the size of the space occupying lesion was about 3.0×2.0×2.0 cm, adjacent to the left abdominal aorta, left renal artery and left renal vein. The space occupying density was similar to that of renal parenchyma in the unenhanced phase, whereas the enhancement was less pronounced in the arterial phase, more pronounced in the venous phase, and the attenuation was less pronounced in the delayed phase. After further refining the preoperative preparation, the surgical approach was "transabdominal 3D laparoscopic left retroperitoneal space occupying resection". Intraoperatively, a space occupying was found at the angle between the abdominal aorta and renal pedicle vessels, which were dark red, soft in quality and had a heavy adhesion to the renal artery. An atraumatic vascular clip was used to block the left renal artery, the gap between the free renal artery and the space occupying, and then the renal artery noninvasive vascular clip was loosened. Continuing free space occupying, we found that the space occupying originated from the left renal vein, gradually enlarged, terminated at the psoas muscle, and connected with the renal vein approximately 1 cm in width. Closely apposed renal veins were blocked with a vascular clip, clipped, and finally a complete resection space was taken. RESULTS: The procedure was uneventful, without trauma to the surrounding tissue organs. After complete resection of retroperitoneal mass, the patient recovered well. No complications were found, and the discomfort symptoms disappeared. The pathological result was renal venous aneurysm, which was considered due to lumbar venous variation. CONCLUSION: No treatment modality for the endoscopic resection of renal venous aneurysms has been documented, and the previous treatment modalities were usually nephrectomy or intervention. This surgical procedure may be the first in the world and open a new way for the diagnosis and treatment of renal venous aneurysms.