ABSTRACT
Artificial enzymes with high stability, adjustable catalytic activity, controllable preparation, and good reproducibility have been widely studied. Noble metal nanozymes, particularly gold nanoparticles (Au NPs), exhibit good catalytic activity, but their stability is poor. In this study, zeolitic imidazolate framework-8 (ZIF-8) was used as a carrier for Au NPs, thus improving the utilization efficiency and conservation stability of the nanozymes. A ZIF-8/Au nanocomposite with peroxidase activity and a raspberry-shaped structure was synthesized. In the assay, ZIF-8/Au catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to a blue product oxidized TMB (oxTMB). Glutathione (GSH) selectively inhibited this reaction, with a detection limit of 0.28 µM and linear range of 0.5-60 µM. Using the photo and chromaticity analysis functions, we developed a portable analysis method using a smartphone equipped with a camera module as a detection terminal for a wide range of rapid screening techniques for GSH. Preparation of raspberry-shaped ZIF-8/Au improved the catalytic activity of Au NPs and good results were demonstrated in serum, which suggests their promising application under physiological conditions.
Subject(s)
Glutathione , Gold , Limit of Detection , Metal Nanoparticles , Gold/chemistry , Glutathione/chemistry , Glutathione/analysis , Glutathione/blood , Metal Nanoparticles/chemistry , Metal-Organic Frameworks/chemistry , Colorimetry/methods , Peroxidase/chemistry , Peroxidase/metabolism , Zeolites/chemistry , Humans , Smartphone , Oxidation-Reduction , Catalysis , Benzidines/chemistryABSTRACT
Diabetic bone defects, exacerbated by hyperglycemia-induced inflammation and oxidative stress, present significant therapeutic challenges. This study introduces a novel injectable scaffold, MgH2@PLGA/F-GM, consisting of foamed gelatin-methacryloyl (GelMA) and magnesium hydride (MgH2) microspheres encapsulated in poly(lactic-co-glycolic acid) (PLGA). This scaffold is uniquely suited for diabetic bone defects, conforming to complex shapes and fostering an environment conducive to tissue regeneration. As it degrades, Mg(OH)2 is released and dissolved by PLGA's acidic byproducts, releasing therapeutic Mg2+ ions. These ions are instrumental in macrophage phenotype modulation, inflammation reduction, and angiogenesis promotion, all vital for diabetic bone healing. Additionally, hydrogen (H2) released during degradation mitigates oxidative stress by diminishing reactive oxygen species (ROS). This multifaceted approach not only reduces ROS and inflammation but also enhances M2 macrophage polarization and cell migration, culminating in improved angiogenesis and bone repair. This scaffold presents an innovative strategy for addressing the complexities of diabetic bone defect treatment.
Subject(s)
Gelatin , Hydrogels , Hydrogen , Magnesium , Gelatin/chemistry , Magnesium/chemistry , Hydrogen/chemistry , Hydrogen/pharmacology , Hydrogen/therapeutic use , Hydrogen/administration & dosage , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Mice , Bone Regeneration/drug effects , Methacrylates/chemistry , Delayed-Action Preparations/chemistry , Macrophages/drug effects , Macrophages/metabolism , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Tissue Scaffolds/chemistry , Reactive Oxygen Species/metabolism , RAW 264.7 Cells , Diabetes Mellitus, Experimental/drug therapy , Male , Oxidative Stress/drug effectsABSTRACT
Background: Obesity is related to various diseases such as endocrine metabolism and cardiovascular diseases. We provide an evidence-based evaluation for the effect of massage on patients with obesity. Methods: Relevant literature published in PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI) and other databases were searched until October 2023. Meta-analysis was performed using RevMan 5.4. A p value less than 0.05 indicates a statistically significant difference. Results: Twelve studies were finally included. Compared with conventional therapy, massage therapy were more effective, mainly in terms of (1) weight [mean difference (MD) = -3.71, 95%CI = -6.51,-0.88]; (2) body mass index (BMI), [MD = -2.00, 95%CI = -3.38, -0.62]; (3) Waist circumference (WC), [MD = -6.24, 95%CI = -8.71, -3.77]; (4) total cholesterol (TC), [MD = -0.65, 95%CI = -1.08, -0.22]; (5) triglycerides (TG), [MD = -0.92, 95%CI = -1.37, -0.47]. Conclusion: Massage therapy may be more effective for patients with obesity than conventional treatment. Given the number of studies and potential heterogeneity, more high-quality randomized controlled trials are needed to confirm our conclusions.
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This study utilized network pharmacology to investigate the effects of Xiaoyaosan (XYS) on the intervention of hyperplasia of mammary glands (HMG) by targeting specific genes and signaling pathways. The active ingredients and targets of XYS, which consisted of 8 traditional Chinese medicines (TCM), were identified using TCMSP. The gene targets associated with HMG were obtained from the GeneCards Database, and the intersection data between the 2 was integrated. Cytoscape 3.8.1 software was used to construct a network diagram illustrating the relationship between compounds, drug active ingredients, target proteins, and the disease. The protein-protein interaction network diagram was generated using STRING, and the core targets were analyzed. A total of 133 active ingredients in XYS and 7662 active ingredient targets were identified. Among them, 6088 targets were related to HMG, and 542 were common targets between the active ingredients and the disease. The protein-protein interaction (PPI) core network contained 15 targets, with 5 key targets playing a crucial role. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses have indicated that XYS has the potential to treat HMG by interfering with the AGE-RAGE signaling pathway in diabetic complications, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Additionally, molecular docking studies have shown excellent binding properties between the drug components and key targets. Thus, this study provides a theoretical foundation for a better understanding of the pharmacological mechanism and clinical application of XYS in the comprehensive treatment of HMG.
Subject(s)
Drugs, Chinese Herbal , Mammary Glands, Human , Humans , Network Pharmacology , Hyperplasia , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Medicine, Chinese Traditional , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic useABSTRACT
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic and progressive condition defined by hyperglycemia caused by abnormalities in insulin production, insulin receptor sensitivity, or both. Several studies have revealed that higher body mass index (BMI) is associated with increasing risk of developing diabetes. In this study, we perform a protocol for systematic review to explore metabolite biomarkers that could be used to identify T2DM in obese subjects. METHODS: The protocol of this review was registered in PROSPERO (CRD42023405518). Three databases, EMBASE, PubMed, and Web of Science were selected to collect potential literature from their inceptions to July December 2023. Data for collection will include title, authors, study subjects, publication date, sample size, detection and analytical platforms, participant characteristics, biological samples, confounding factors, methods of statistical analysis, the frequency and directions of changes in potential metabolic biomarkers, and major findings. Pathway analysis of differential metabolites will be performed with MetaboAnalyst 5.0 based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Human Metabolome Database. RESULTS: The results of this systematic review will be published in a peer-reviewed journal. CONCLUSION: This systematic review will summarize the potential biomarkers and metabolic pathways to provide a new reference for the prevention and treatment of T2DM in obese subjects.
Subject(s)
Diabetes Mellitus, Type 2 , Hyperglycemia , Insulin Resistance , Humans , Diabetes Mellitus, Type 2/complications , Systematic Reviews as Topic , Obesity/complications , Research Design , Biomarkers , Review Literature as TopicABSTRACT
Elevated Gamma-glutamyl transferase (GGT) levels are often suggestive of cholelithiasis, and previous studies have indicated that GGT is highly expressed in the urinary system. Therefore, we hypothesized that there may be an association between GGT levels and calculus of kidney (CK) incidence. To investigate this potential causal relationship, we employed Mendelian randomization (MR) analysis. Additionally, we analyzed the levels of other liver enzymes, including alanine transaminase (ALT) and alkaline phosphatase (ALP). The relationship between GGT levels and CK incidence was analyzed using two-sample Mendelian randomization. Summary Genome-Wide Association Studies data were utilized for this analysis. 33 single nucleotide polymorphisms known to be associated with GGT levels were employed as instrumental variables. We employed several MR methods including IVW (inverse variance weighting), MR-Egger, weighted median, weighted mode, and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier). Furthermore, we conducted tests for horizontal multivariate validity, heterogeneity, and performed leave-one-out analysis to ensure the stability of the results. Overall, several MR methods yielded statistically significant results with a p-value < 0.05. The results from the IVW analysis yielded an odds ratio (OR) of 1.0062 with a 95% confidence interval (CI) of 1.0016-1.0109 (p = 0.0077). Additional MR methods provided supplementary results: MR-Egger (OR 1.0167, 95% CI 1.0070-1.0266, p = 0.0040); weighted median (OR 1.0058, 95% CI 1.0002-1.0115, p = 0.0423); and weighted mode (OR 1.0083, 95% CI 1.0020-1.0146, p- = 0.0188). Sensitivity analyses did not reveal heterogeneity or outliers. Although potential horizontal pleiotropy emerged, we speculate that this could be attributed to inadequate test efficacy. However, subsequent use of MR-PRESSO did not provide evidence of pleiotropy. Our analysis suggests a positive association between elevated GGT levels and CK incidence, indicating an increased risk of CK development. However, no causal relationship was observed between levels of ALP or ALT and CK incidence.
Subject(s)
Kidney Calculi , gamma-Glutamyltransferase , Humans , gamma-Glutamyltransferase/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Kidney Calculi/epidemiology , Kidney Calculi/genetics , Alanine Transaminase , Alkaline Phosphatase , Coloring Agents , Ubiquitin-Protein Ligases , KidneyABSTRACT
Introduction: The feasibility of using a steel decalcified bone matrix (DBM)-reinforced concrete engineered cartilage gel (ECG) model concept for in vivo cartilage regeneration has been demonstrated in preliminary experiments. However, the regenerated cartilage tissue contained an immature part in the center. The present study aimed to achieve more homogeneous regenerated cartilage based on the same model concept. Methods: For this, we optimized the culture conditions for the engineered cartilage gel-decalcified bone matrix (ECG-DBM) complex based on the previous model and systematically compared the in vitro chondrogenic abilities of ECG in the cartilage slice and ECG-DBM complex states. We then compared the in vivo cartilage regeneration effects of the ECG-DBM complex with those of an equivalent volume of ECG and an equivalent ECG content. Results and discussion: Significant increases in the DNA content and cartilage-specific matrix content were observed for the ECG-DBM complex compared with the ECG cartilage slice, suggesting that the DBM scaffold significantly improved the quality of ECG-derived cartilage regeneration in vitro. In the in vivo experiments, high-quality cartilage tissue was regenerated in all groups at 8 weeks, and the regenerated cartilage exhibited typical cartilage lacunae and cartilage-specific extracellular matrix deposition. Quantitative analysis revealed a higher chondrogenic efficiency in the ECG-DBM group. Specifically, the ECG-DBM complex achieved more homogeneous and stable regenerated cartilage than an equivalent volume of ECG and more mature regenerated cartilage than an equivalent ECG content. Compared with ECG overall, ECG-DBM had a more controllable shape, good morphology retention, moderate mechanical strength, and high cartilage regeneration efficiency. Further evaluation of the ECG-DBM complex after in vitro culture for 7 and 14 days confirmed that an extended in vitro preculture facilitated more homogeneous cartilage regeneration.
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Hair loss is a growing esthetic condition driven by complex mechanisms that has numerous psycho-social implications. Conventional drug applications usually focus on a single treatment target, and the penetration depth restricts the post-delivery effect. Method: We fabricated a curcumin-zinc framework (ZnMOF) encapsulated gamma-polyglutamic acid (γ-PGA) microneedle patch (ZnMOF-MN) as a multifunctional biosafe transdermal drug delivery system. ZnMOF was characterized with the field emission scanning electron microscope (FE-SEM), dynamic light scattering (DLS), elemental mapping, and X-ray diffraction (XRD). The topographical and hygroscopic features of ZnMOF-MN were characterized with SEM. The in vitro ZnMOF release profile and the in vivo penetration of ZnMOF-MN were also evaluated. The anti-oxidant, anti-apoptosis, and antiandrogen effects of ZnMOF solution and ZnMOF-MN extract were studied on mouse dermal papilla cells (DPCs). Two animal models (in C57BL/6 mice), including androgenic alopecia (AGA) model and wound healing model, were used to identify the therapeutic effect of ZnMOF-MN on hair regrowth and wound healing in vivo. Hair follicles, surrounding vessels (CD31+), and proliferating cells (Ki67+) were evaluated by histological staining. Results: ZnMOF crystals were cone-shaped nanoparticles with a size distribution of 424.9 ± 59.01 nm. ZnMOF-MN patch can create temporary holes in the skin to directly and evenly deliver bioactive ZnMOF particles to the targeted depth and achieve a steady and sustained release of Zn2+ and curcumin. In vitro, ZnMOF significantly improved the viability of DPCs against the excess reactive oxygen species (ROS) and inhibited the apoptosis induced by zinc deficiency. In addition, it also reversed the inhibitory effects of dihydrotestosterone (DHT) infiltration. Moreover, the ZnMOF-MN treatment has been proved to accelerate wound healing and increase hair follicles in wound healing models, and improved the hair regrowth in AGA animal models. Enhanced capillary density and cell proliferation observed in the CD31+ and Ki67+ staining of ZnMOF-MN group in both animal models also suggested that ZnMOF can facilitate angiogenesis and promote cell proliferation in the skin, respectively. Conclusion: The ZnMOF-MN treatment is a comprehensive solution with excellent therapeutic efficacy and patient-friendly features for promoting hair growth under various clinical conditions.
Subject(s)
Curcumin , Mice , Animals , Curcumin/pharmacology , Curcumin/therapeutic use , Zinc/pharmacology , Ki-67 Antigen , Mice, Inbred C57BL , Hair , Alopecia/drug therapy , Drug Delivery Systems , Organic Chemicals/pharmacologyABSTRACT
Antibiotics are commonly used to treat bacterial infections, but the misuse and abuse of antibiotics have given rise to a severe problem of the drug resistance of bacteria. Solving this problem has been a vitally important task in the modern medical arena. Antibacterial peptide (AMPs) has become a promising candidate drug to replace antibiotics because of their broad-spectrum antibacterial activity and their difficulty in making bacteria resistant. However, its wider clinical application is limited by the shortcomings of high cytotoxicity and low antibacterial efficiency. In this paper, we constructed an antibacterial peptide (Cu-GGH-KKLRKIAFK, abbreviated as Cu-GGH-AMP) with a DNA cleavage function. The peptide has two functional regions, the C-terminal antibacterial peptide PaDBS1R6F10 (KKLRLKIAFK) and the N-terminal Cu-GGH complex. PaDBS1R6F10 is a unique antibacterial peptide, which shows lower tendency to produce bacterial resistance than traditional antibiotics. Cu-GGG complexes are formed by chelating Cu with the classical amino terminal Cu (II)- and Ni (II) -Binding (ATCUN) motif GGH. In the presence of ascorbic acid, Cu-GGH can efficiently catalyze the oxidative cleavage of bacterial DNA, thus playing a synergistic antibacterial role with antibacterial peptides. The in vitro and in vivo experiments demonstrated this functionalized antibacterial peptide possesses excellent antibacterial and anti-skin infection capability, as well as the activity of promoting wound healing.
Subject(s)
Anti-Infective Agents , Disinfection , DNA Cleavage , Copper/pharmacology , Copper/chemistry , Peptides/pharmacology , Peptides/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , BacteriaABSTRACT
The COVID-19 pandemic has changed the mobility, accessibility, and behaviors of visitors dramatically. Under the impact of COVID-19, the social carrying capacity and emotion dynamics in parks and recreation areas are expected to change due to the uncertainty of health risks associated with visitors' behaviors. This study conducted an on-site visitor survey at Leiqiong Global Geological Park, a national park located in urban-proximate areas in Haikou, China. This study aims to examine factors impacting visitors' perceived crowding and emotions under varying levels of visitor use in urban national parks in the context of COVID-19. Study results suggest that visitors have the highest level of motivation for scenery and culture viewing and are generally satisfied with the environmental quality and design and COVID-19 prevention strategies and implementation efforts within the park. Moreover, this study suggests that the level of crowding and COVID-19 prevention strategies and implementation can affect visitors' emotions in urban natioanl parks significantly. These findings highlight the importance of enforcing the social carrying capacity limits and COVID-19 prevention strategies for urban parks and protected areas to mitigate physical and mental health risks during the COVID-19 pandemic. Management implication: This study is one of the pilot studies that examines the social carrying capacity and emotion dynamics in urban national parks under the impact of the COVID-19 pandemic. Study results identify the thresholds of social carrying capacity and visitors' positive emotions based on the indicator of People Per View (PPV). Moreover, COVID-19 prevention strategies (e.g., mask-wearing and social distancing) can reduce visitors' perceived crowding and enhance positive emotions. These findings suggest that urban national parks should monitor visitor use levels based on the social carrying capacity framework to reduce visitors' perceived crowding and maintain positive emotions in the post-COVID-19 era.
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Constructed on the total-factor analysis framework, this paper develops a comprehensive evaluation system and adopts the Super-SBM model to both analyze and enunciate the characteristics of tourism eco-efficiency in China during 2000-2017. This paper also identifies the determinants associated with spatial differentiation of tourism eco-efficiency by employing a novel geographical technique, namely the Geographical Detector Model. The results indicate that the tourism eco-efficiency exhibits great potential for growth. Besides, pure technical efficiency drives the optimized development of eco-efficiency. Also, there is significant spatial variations in eco-efficiency across different provinces and regions in China. Urbanization contributes to tourism eco-efficiency remarkably, followed by openness, technical level, economic scale, industrial structure, capital effect, environmental regulation, and tourism growth. The relational interrelations of tourism eco-efficiency determinants are the bi-enhancement and the nonlinear-enhancement interactions. The implications of research findings are discussed and may be applied to a multitude of corporate environmental-economic management scenarios.
Subject(s)
Tourism , Urbanization , China , Economic Development , Efficiency , IndustryABSTRACT
Purpose: Given the digital transformation of service businesses by providing online food services and the influence of online reviews on consumers' purchasing decisions, this study examines how service recovery attributes in different stages influence relationship marketing strategies, i.e., relationship quality and customer loyalty after service failure. This study is built upon a revised service recovery cycle model by accounting for three stages and their corresponding attributes; whereon a conceptual stage model of service recovery is proposed. This conceptual stage model incorporates stages of service recovery, their respective attributes, and how they influence relationship marketing strategies. Design/methodology/approach: An online marketing company was employed for data collection in 2019, which resulted in 301 valid responses. A Structural Equation Model (SEM) was conducted with all the data to test the relationships between the constructs. The individual measurement model was tested using the Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). A structural model was estimated using AMOS to test all the hypotheses. Findings: The findings demonstrate that the attributes (i.e., response speed, compensation) paired with the first two stages of service recovery can significantly influence consumer loyalty in a positive state. The findings also manifest the intermediary role that relationship quality has played in the association of service recovery and consumer loyalty, which implies that the food delivery businesses could attain a more comprehended relationship quality with consumers through active and timely compensatory service recovery consumer loyalty to the food businesses. Originality/value: This study examines how these different stages of the service recovery cycle influence the decision-making of relationship marketing strategies (i.e., relationship quality, customer loyalty) on the prerequisite of service failure. This study aspires to expand the service recovery research by objectifying a conceptual stage model of service recovery, incorporating stages' recovery attributes and how these recovery attributes reciprocally influence relationship quality and customer loyalty.
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Background: Quick and accurate identification of urinary calculi patients with positive urinary cultures is critical to the choice of the treatment strategy. Predictive models based on machine learning algorithms provide a new way to solve this problem. This study aims to determine the predictive value of machine learning algorithms using a urine culture predictive model based on patients with urinary calculi. Methods: Data were collected from four clinical centers in the period of June 2016, to May 2019. 2,054 cases were included in the study. The dataset was randomly split into ratios of 5:5, 6:4, and 7:3 for model construction and validation. Predictive models of urine culture outcomes were constructed and validated by logistic regression, random forest, adaboost, and gradient boosting decision tree (GBDT) models. Each ratio's construction and verification were repeated five times independently for cross-validation. The Matthews correlation coefficient (MMC), F1-score, receiver operating characteristic (ROC) curve with the area under curve (AUC) was used to evaluate the performance of each prediction model. The additive net reclassification index (NRI) and absolute NRI were used to assess the predictive capabilities of the models. Results: Four prediction models of urinary culture results in patients with urinary calculi were constructed. The mean AUCs of the logistic regression, random forest, adaboost, and GBDT models were 0.761 (95% CI: 0.753-0.770), 0.790 (95% CI: 0.782-0.798), 0.779 (95% CI: 0.766-0.791), and 0.831 (95% CI: 0.823-0.840), respectively. Moreover, the average MMC and F1-score of GBDT model was 0.460 and 0.588, which was improved compared to logistic regression model of 0.335 and 0.501. The additive NRI and absolute NRI of the GBDT and logistic regression models were 0.124 (95% CI: 0.106-0.142) and 0.065 (95% CI: 0.060-0.069), respectively. Conclusions: Our results indicate that machine learning algorithms may be useful tools for urine culture outcome prediction in patients with urinary calculi because they exhibit superior performance compared with the logistic regression model.
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Dressing with the function of anti-wound infection and promoting skin repair plays an important role in medicine, beauty industry, etc. In terms of anti-wound infection, traditional dressings, such as gauze, have problems such as excessive bleeding in the process of contact or removal, and slow wound healing due to poor biological compatibility. The development of new functional and biocompatible dressings has essential application value in biomedical fields. In this study, a new type of dressing based on polypeptide functional sponge patch was constructed. The porous sponge patch is made of antimicrobial peptide and medical agarose through gel and freeze-drying technology. In vitro antibacterial experiments and small animal skin wound infection model experiments show that the porous sponge has excellent antibacterial and anti-skin infection activities, as well as the function of promoting wound healing.
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BACKGROUND: Atrial fibrillation is a type of persistent arrhythmia that can lead to serious complications. Therefore, accurate and quick detection of atrial fibrillation by surface electrocardiogram has great importance on further treatment. The practical electrocardiogram signals contain various interferences in different frequencies, such as myoelectricity interference, power interference and so on. Detection speed and accuracy largely depend on the atrial fibrillation signal features extracted by the algorithm. But some of the discovered atrial fibrillation features are not well distinguishable, resulting in poor classification effect. METHODS: This paper proposed a high distinguishable frequency feature-the frequency corresponding to the maximum amplitude in the frequency spectrum. We used the R-R interval detection method optimized with the mathematical morphology method and combined with the wavelet transform method for analysis. According to the two features-the maximum amplitude in the frequency spectrum and R-R interval irregular, we could recognize atrial fibrillation signals in electrocardiogram signals by decision tree classification algorithm. RESULTS: The data used in the experiment come from the MIT-BIH database, which is publicly accessible via the web and with ethical approval and consent. Based on the input of time-domain and frequency-domain features, we classified sinus rhythm signals and AF signals using the decision tree generated by classification and regression tree (CART) algorithm. From the confusion matrix, we got the accuracy was 98.9%, sensitivity was 97.93% and specificity was 99.63%. CONCLUSIONS: The experimental results can prove the validity of the maximum amplitude in the frequency spectrum and the practicability and accuracy of the detection method, which applied this frequency-domain feature. Through the detection method, we obtained good accuracy of classifying sinus rhythm signals and atrial fibrillation signals. And the sensitivity and specificity of our method were pretty good by comparison with other studies.
Subject(s)
Atrial Fibrillation/diagnostic imaging , Decision Trees , Electrocardiography , Algorithms , Databases, Factual , Humans , Sensitivity and SpecificityABSTRACT
BACKGROUND: To investigate whether hsa_circ_0000520 affects Herceptin resistance in gastric cancer by regulating the PI3K-AKT signaling. METHODS: The expression of hsa_circ_0000520 was detected by qRT-PCR in gastric cancer tissues and cell lines. A Herceptin-resistant gastric cancer cell was established. PcDNA and pcDNA-hsa_circ_0000520 were transfected into NCI-N87R cells and treated with Herceptin at a concentration of 10 µg/mL for 24 hours. MTT tested cell proliferation, and apoptosis was measured by flow cytometry. IGF-1 treatment was used to activate PI3K-Akt signaling. The expression levels of related proteins were detected. RESULTS: The expression of hsa_circ_0000520 was reduced in gastric cancer tissues and cell lines, and hsa_circ_0000520 in NCI-N87R cells was significantly lower than that of NCI-N87 cells. Compared with the CON group, the cell viability of the Herceptin group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of Bcl-2, p-PI3K, and p-Akt protein were significantly reduced. Compared with the Herceptin + pcDNA group, the cell viability of the Herceptin + hsa_circ_0000520 group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of p-PI3K and p-Akt proteins were significantly reduced. After IGF-1 treatment, the cell viability was significantly increased, the apoptosis rate was significantly reduced, the level of Bax protein was significantly reduced, and the level of Bcl-2 protein was significantly increased. CONCLUSION: Hsa_circ_0000520 overexpression may reverse the Herceptin resistance of gastric cancer cells by inhibiting the PI3K-Akt signaling pathway.
Subject(s)
Drug Resistance, Neoplasm/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Circular/metabolism , Signal Transduction , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Trastuzumab/therapeutic use , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Middle Aged , RNA, Circular/genetics , Signal Transduction/drug effects , Trastuzumab/pharmacologyABSTRACT
It has previously been determined that long non-coding (lnc)RNA-zinc finger protein (ZNF)281 serves an oncogenic role in breast cancer; however, the role of lncRNA-ZNF281 in other cancer types is yet to be elucidated. The present study aimed to analyze the role of ZNF281 in gastric cancer by characterizing its activity in cancerous tissues and normal tissues using RT-qPCR. Overexpression experiments were also performed to investigate the interaction between ZNF281 and miR-124, and Transwell assays were conducted to analyze cell invasion and migration. The present study revealed that lncRNA-ZNF281 was upregulated, and that microRNA (miR)-124 was downregulated, in cancerous tissues compared with that in the paired adjacent healthy tissues of patients with gastric cancer. In addition, the expression levels of lncRNA-ZNF281 and miR-124 exhibited a significant inverse association. Furthermore, in vitro cell experiments determined that lncRNA-ZNF281 overexpression resulted in miR-124 inhibition, yet miR-124 overexpression did not influence lncRNA-ZNF281 expression. lncRNA-ZNF281 expression level was also associated with the clinical stage of the patient. Bioinformatics analysis revealed that lncRNA-ZNF281 may target the base pairs in the hairpin loop of the miR-124 precursor. Subsequent in vitro cell experiments indicated that lncRNA-ZNF281 overexpression resulted in promoting the migration and invasiveness of gastric cancer cells, while miR-124 over-expression led to its inhibition. In addition, miR-124 overexpression partially recovered the effects of lncRNA-ZNF281 overexpression. Therefore, lncRNA-ZNF281 may promote cancer cell migration and invasion in gastric cancer via downregulation of miR-124.
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Objective: To assess the therapeutic efficiency of radiofrequency ablation (RFA) for colorectal liver metastases (CRLM) in the caudate lobe compared with that of surgical resection.Methods: After approved by institutional review board, we retrospectively reviewed 20 patients with caudate CRLM treated by RFA or resection between 2006 and 2017. Comparative analysis was performed based on the different therapies, including patient characteristics, therapeutic outcomes, recurrences, and survivals.Results: During the median follow-up of 7 years (range, 2 -11 years), no differences in complications and recurrences were found between RFA and surgery groups (p > .05). The median overall survival (OS) of patients after RFA and resection were 41 months (95% confidence interval (CI) 23.5-70.5) and 54 months (95% CI 31.1-77.7), respectively (p = .627, hazard radio (HR) 0.7, 95% CI 0.2-2.6). However, OS of resection group was better than that of RFA group for large caudate CRLMs (>3 cm) (p = .042, HR 4.4, 95% CI 0.6-32.6).Conclusions: RFA is a feasible, safe, and effective treatment for CRLM in the caudate. Surgical resection revealed superior outcomes in the treatment of caudate CRLMs, particularly in cases with a hepatic tumor size >3 cm.
Subject(s)
Adenocarcinoma/surgery , Colorectal Neoplasms/pathology , Hepatectomy , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Radiofrequency Ablation , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Aged , Colorectal Neoplasms/mortality , Colorectal Neoplasms/therapy , Female , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
In contrast to classical physics, quantum theory demands that not all properties can be simultaneously well defined; the Heisenberg uncertainty principle is a manifestation of this fact. Alternatives have been explored--notably theories relying on joint probability distributions or non-contextual hidden-variable models, in which the properties of a system are defined independently of their own measurement and any other measurements that are made. Various deep theoretical results imply that such theories are in conflict with quantum mechanics. Simpler cases demonstrating this conflict have been found and tested experimentally with pairs of quantum bits (qubits). Recently, an inequality satisfied by non-contextual hidden-variable models and violated by quantum mechanics for all states of two qubits was introduced and tested experimentally. A single three-state system (a qutrit) is the simplest system in which such a contradiction is possible; moreover, the contradiction cannot result from entanglement between subsystems, because such a three-state system is indivisible. Here we report an experiment with single photonic qutrits which provides evidence that no joint probability distribution describing the outcomes of all possible measurements--and, therefore, no non-contextual theory--can exist. Specifically, we observe a violation of the Bell-type inequality found by Klyachko, Can, Binicioglu and Shumovsky. Our results illustrate a deep incompatibility between quantum mechanics and classical physics that cannot in any way result from entanglement.