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1.
PLoS One ; 19(3): e0299027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38442120

RESUMO

High-precision waveform identification and measurement are effective for waveform detection and evaluation in signal processing. The accuracy of waveform identification, precision of measurement, and speed of response are important indicators of waveform measurement instruments. To detect the waveform accurately, a hold and attenuation circuit divided into two is designed, and the STM32F4 microcontroller is used to accurately capture and perform spectrum analysis using a high-precision analog-to-digital converter based on fast Fourier transform technology to identify key parameters, such as waveform type, frequency, peak-to-peak value, and duty cycle. To improve the recognition accuracy and response speed, technical solutions, such as high-frequency sampling and over-zero detection, are used to improve the system efficiency. Algorithm simulation, circuit simulation, and physical testing show that the high-precision waveform synchronization recognition circuit and algorithm can accurately recognize various essential waveforms in the voltage and frequency ranges of 50 mV ≤ VPP ≤ 10 V and 1 Hz ≤ f ≤ 50 kHz, respectively, and simultaneously measure important parameters, such as frequency, peak-to-peak value, and duty cycle with an accuracy within ±1%. Intelligent linkage, no intermediate parameter setting, and a response speed of approximately 0.3 s make it suitable for such applications as fast and high-precision waveform intelligent detection and display. The method is highly integrated, simple to operate, cost-effective, and practical.


Assuntos
Algoritmos , Inteligência , Simulação por Computador , Exame Físico , Tecnologia
2.
Nitric Oxide ; 142: 47-57, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38049061

RESUMO

BACKGROUND: Endothelial-mesenchymal transition (EndMT) induced by low shear stress plays an important role in the development of atherosclerosis. However, little is known about the correlation between hydrogen sulfide (H2S), a protective gaseous mediator in atherosclerosis and the process of EndMT. METHODS: We constructed a stable low-shear-stress-induced(2 dyn/cm2) EndMT model, acombined with the pretreatment method of hydrogen sulfide slow release agent(GYY4137). The level of MEST was detected in the common carotid artery of ApoE-/- mice with local carotid artery ligation. The effect of MEST on atherosclerosis development in vivo was verified using ApoE-/- mice were given tail-vein injection of endothelial-specific overexpressed and knock-down MEST adeno-associated virus (AAV). RESULTS: These findings confirmed that MEST is up-regulated in low-shear-stress-induced EndMT and atherosclerosis. In vivo experiments showed that MEST gene overexpression significantly promoted EndMT and aggravated the development of atherosclerotic plaques and MEST gene knockdown significantly inhibited EndMT and delayed the process of atherosclerosis. In vitro, H2S inhibits the expression of MEST and EndMT induced by low shear stress and inhibits EndMT induced by MEST overexpression. Knockdown of NFIL3 inhibit the up regulation of MEST and EndMT induced by low shear stress in HUVECs. CHIP-qPCR assay and Luciferase Reporter assay confirmed that NFIL3 binds to MEST DNA, increases its transcription and H2S inhibits the binding of NFIL3 and MEST DNA, weakening NFIL3's transcriptional promotion of MEST. Mechanistically, H2S increased the sulfhydrylation level of NFIL3, an important upstream transcription factors of MEST. In part, transcription factor NFIL3 restrain its binding to MEST DNA by sulfhydration. CONCLUSIONS: H2S negatively regulate the expression of MEST by sulfhydrylation of NFIL3, thereby inhibiting low-shear-stress-induced EndMT and atherosclerosis.


Assuntos
Aterosclerose , Sulfeto de Hidrogênio , Camundongos , Animais , Humanos , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Transição Endotélio-Mesênquima , Aterosclerose/genética , Aterosclerose/metabolismo , Endotélio/metabolismo , DNA/metabolismo , Apolipoproteínas E/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Transição Epitelial-Mesenquimal
3.
Front Neurosci ; 17: 998017, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37008213

RESUMO

Different interacting contexts influence the decision-making process, as revealed by the computational modeling. Through four studies, we investigated how smartphone addiction and anxiety influenced impulsive behaviors, along with the underlying psychological mechanisms and dynamic decision-making processes. In the first and second studies, we found no significant correlation between smartphone addiction and impulsive behavior. However, in the third study, we found that smartphone separation increased impulsive decision-making and purchases, and state anxiety, but not trait anxiety, mediated this effect. We explored the dynamic decision-making process using a multi-attribute drift diffusion model (DDM). The results showed that anxiety triggered by smartphone separation changed the trade-offs between decision weights for the fundamental components of the dynamic choice process. In the fourth study, we investigated why smartphone addiction led to increased anxiety and found that extended-self was a mediating factor. Our findings show that smartphone addiction was not correlated with impulsive behaviors, but was correlated with state anxiety in the context of smartphone separation. Further, this study shows how emotional states triggered by different interacting contexts affect the dynamic decision-making process and consumer behaviors.

4.
Curr Med Chem ; 30(16): 1848-1859, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35786179

RESUMO

Ferroptosis is an iron-dependent cell death, characterized by the accumulation of lipid-reactive oxygen species; various regulatory mechanisms influence the course of ferroptosis. The rapid increase in cardiovascular diseases (CVDs) is an extremely urgent problem. CVDs are characterized by the progressive deterioration of the heart and blood vessels, eventually leading to circulatory system disorder. Accumulating evidence, however, has highlighted crucial roles of ferroptosis in CVDs. Hydrogen sulfide plays a significant part in anti-oxidative stress, which may participate in the general mechanism of ferroptosis and regulate it by some signaling molecules. This review has primarily summarized the effects of hydrogen sulfide on ferroptosis and cardiovascular disease, especially the antioxidative stress, and would provide a more effective direction for the clinical study of CVDs.


Assuntos
Doenças Cardiovasculares , Ferroptose , Sulfeto de Hidrogênio , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Morte Celular , Coração , Espécies Reativas de Oxigênio , Peroxidação de Lipídeos
5.
World J Clin Cases ; 10(30): 11016-11022, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36338198

RESUMO

BACKGROUND: The VPS33B (OMIM: 608552) gene is located on chromosome 15q26.1. We found a female infant with autosomal recessive arthrogryposis, renal dysfunction and cholestasis syndrome 1 (ARCS1) caused by mutation in VPS33B. The child was diagnosed with ARCS1 (OMIM: 208085) after the whole exome sequencing revealed two heterozygous mutations (c.96+1G>C, c.242delT) in the VPS33B gene. CASE SUMMARY: We report a Chinese female infant with neonatal cholestasis disorder, who was eventually diagnosed with ARCS1 by genetic analysis. Genetic testing revealed two new mutations (c.96+1G>C and c.242delT) in VPS33B, which is the causal gene. The patient was compound heterozygous, and her parents were both heterozygous. CONCLUSION: This study extends the mutational spectrum of the VPS33B gene to provide a molecular basis for the etiological diagnosis of ARCS1 and for genetic counseling of the family.

6.
Biomed Opt Express ; 13(6): 3401-3415, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35781968

RESUMO

Real-time multi-emitter fitting is a key technology for advancing super-resolution localization microscopy (SRLM), especially when it is necessary to achieve dynamic imaging quality control and/or optimization of experimental conditions. However, with the increase of activation densities, the requirements in the computing resources would increase rapidly due to the complexity of the fitting algorithms, making it difficult to realize real-time multi-emitter fitting for emitter density more than 0.6 mol/µm2 in large field of view (FOV), even after acceleration with the popular Graphics Processing Unit (GPU) computation. Here we adopt the task parallelism strategy in computer science to construct a Peripheral Component Interconnect Express (PCIe) based all-in-one heterogeneous computing platform (AIO-HCP), where the data between two major parallel computing hardware, Field Programmable Gate Array (FPGA) and GPU, are interacted directly and executed simultaneously. Using simulated and experimental data, we verify that AIO-HCP could achieve a data throughput of up to ∼ 1.561 GB/s between FPGA and GPU. With this new platform, we develop a multi-emitter fitting method, called AIO-STORM, under big data stream parallel scheduling. We show that AIO-STORM is capable of providing real-time image processing on raw images with 100 µm × 100 µm FOV, 10 ms exposure time and 5.5 mol/µm2 structure density, without scarifying image quality. This study overcomes the data throughput limitation of heterogeneous devices, demonstrates the power of the PCIe-based heterogeneous computation platform, and offers opportunities for multi-scale stitching of super-resolution images.

7.
J Clin Ultrasound ; 50(2): 198-200, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34398457

RESUMO

Interrupted aortic arch (IAA) is a rare complex congenital heart disease characterized by interrupted continuity between ascending aorta and descending aorta. Prenatal diagnosis of IAA by echocardiography is not uncommonly reported despite its rarity. However, employing four-dimensional ultrasound HD-flow imaging and spatiotemporal image correlation (STIC) in diagnosis of this condition has seldom been reported. We report a case of fetal IAA prenatally diagnosed by two-dimensional echocardiography and HD-flow STIC.


Assuntos
Ecocardiografia Quadridimensional , Cardiopatias Congênitas , Aorta Torácica/diagnóstico por imagem , Feminino , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal
8.
Mol Cell Biochem ; 477(1): 255-265, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34687394

RESUMO

Diabetic cardiomyopathy (DCM) is a cardiovascular complication that tends to occur in patients with diabetes, obesity, or insulin resistance, with a higher late mortality rate. Sustained hyperglycemia, increased free fatty acids, or insulin resistance induces metabolic disorders in cardiac tissues and cells, leading to myocardial fibrosis, left ventricular hypertrophy, diastolic and/or systolic dysfunction, and finally develop into congestive heart failure. The close connection between all signaling pathways and the complex pathogenesis of DCM cause difficulties in finding effective targets for the treatment of DCM. It reported that hydrogen sulfide (H2S) could regulate cell energy substrate metabolism, reduce insulin resistance, protect cardiomyocytes, and improve myocardial function by acting on related key proteins such as differentiation cluster 36 (CD36) and glucose transporter 4 (GLUT4). In this article, the relative mechanisms of H2S in alleviating metabolic disorders of DCM were reviewed, and how H2S can better prevent and treat DCM in clinical practice will be discussed.


Assuntos
Cardiomiopatias Diabéticas/metabolismo , Metabolismo Energético , Sulfeto de Hidrogênio/metabolismo , Resistência à Insulina , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Humanos
9.
Opt Express ; 29(22): 35247-35260, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34808963

RESUMO

The real-time multi-emitter localization method is essential for advancing high-throughput super-resolution localization microscopy (HT-SRLM). In the past decade, the graphics processing unit (GPU) computation has been dominantly used to accelerate the execution speed of the multi-emitter localization method. However, if HT-SRLM is combined with a scientific complementary metal-oxide-semiconductor (sCMOS) camera working at full frame rate, real-time image processing is still difficult to achieve using this acceleration approach, thus resulting in a massive data storage challenge and even system crash. Here we take advantage of the cooperative acceleration power of field programming gate array (FPGA) computation and GPU computation, and propose a method called HCP-STORM to enable real-time multi-emitter localization. Using simulated images, we verified that HCP-STORM is capable of providing real-time image processing for raw images from a representative Hamamatsu Flash 4 V3 sCMOS camera working at full frame rate (that is, 2048×2048 pixels @ 10 ms exposure time). Using experimental images, we prove that HCP-STORM is 25 times faster than QC-STORM and 295 times faster than ThunderSTORM, with a small but acceptable degradation in image quality. This study shows the potential of FPGA-GPU cooperative computation in accelerating multi-emitter localization, and pushes a significant step toward the maturity of HT-SRLM technology.

10.
Clin Chim Acta ; 523: 325-329, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34666031

RESUMO

Atherosclerosis (AS) is the pathological basis of numerous lethal diseases, such as myocardial infarction, heart failure, and stroke. As we know, almost twenty million people worldwide die of the arterial diseases annually. Sestrin2 is a stress-inducing protein, which serves as a guardian by activating AMPK, inhibiting mTOR, and maintaining redox balance beneath various stress environments. A large number of studies show that Sestrin2 would shield the body from injury by stress. Moreover, it has been demonstrated that Sestrin2 is closely connected with AS. Here, this article reviewed the involvement of Sestrin2 in the pathogenesis of AS from four aspects: cellular mechanism, oxidative stress, inflammation, and lipid metabolism. Current evidence reveals that Sestrin2 is a novel target for the prevention and treatment of AS.


Assuntos
Aterosclerose , Infarto do Miocárdio , Humanos , Inflamação , Oxirredução , Estresse Oxidativo
11.
Cell Cycle ; 20(15): 1477-1486, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34266366

RESUMO

Endothelial-mesenchymal transition (EndMT) is widely involved in the occurrence and development of cardiovascular diseases. Although there is no direct evidence, it is very promising as an effective target for the treatment of these diseases. Endothelial cells need to respond to the complex cardiovascular environment through EndMT, but sustained stimuli will cause the imbalance of EndMT. Blocking the signal transduction promoting EndMT is an effective method to control the imbalance of EndMT. In particular, we also discussed the potential role of endothelial cell apoptosis and autophagy in regulating the imbalance of EndMT. In addition, promoting mesenchymal-endothelial transformation (MEndT) is also a method to control the imbalance of EndMT. However, targeting EndMT to treat cardiovascular disease still faces many challenges. By reviewing the research progress of EndMT, we have put forward some insights and translated them into challenges and opportunities for new treatment strategies for cardiovascular diseases.


Assuntos
Doenças Cardiovasculares/patologia , Células Endoteliais/patologia , Transição Epitelial-Mesenquimal , Animais , Apoptose , Autofagia , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Plasticidade Celular , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Fenótipo , Transdução de Sinais
12.
Eur J Pharmacol ; 896: 173916, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33529724

RESUMO

Cardiovascular diseases are the leading cause of death and morbidity worldwide. Atherosclerotic cardiovascular disease (ASCVD) is affected by both environmental and genetic factors. Microenvironmental disorders of the human gut flora are associated with a variety of health problems, not only gastrointestinal diseases, such as inflammatory bowel disease, but also extralintestinal organs. Hydrogen sulfide (H2S) is the third gas signaling molecule other than nitric oxide and carbon monoxide. In the cardiovascular system, H2S plays important roles in the regulation of blood pressure, angiogenesis, smooth muscle cell proliferation and apoptosis, anti-oxidative stress, cardiac functions. This review is aiming to explore the potential role of gut microbiota in the development of atherosclerosis through hydrogen sulfide production as a novel therapeutic direction for atherosclerosis.


Assuntos
Artérias/metabolismo , Aterosclerose/microbiologia , Bactérias/metabolismo , Gasotransmissores/metabolismo , Microbioma Gastrointestinal , Sulfeto de Hidrogênio/metabolismo , Intestinos/microbiologia , Animais , Artérias/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/terapia , Humanos , Placa Aterosclerótica , Transdução de Sinais
13.
Mol Cell ; 81(4): 691-707.e6, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33382985

RESUMO

Aerobic glycolysis, or preferential fermentation of glucose-derived pyruvate to lactate despite available oxygen, is associated with proliferation across many organisms and conditions. To better understand that association, we examined the metabolic consequence of activating the pyruvate dehydrogenase complex (PDH) to increase pyruvate oxidation at the expense of fermentation. We find that increasing PDH activity impairs cell proliferation by reducing the NAD+/NADH ratio. This change in NAD+/NADH is caused by increased mitochondrial membrane potential that impairs mitochondrial electron transport and NAD+ regeneration. Uncoupling respiration from ATP synthesis or increasing ATP hydrolysis restores NAD+/NADH homeostasis and proliferation even when glucose oxidation is increased. These data suggest that when demand for NAD+ to support oxidation reactions exceeds the rate of ATP turnover in cells, NAD+ regeneration by mitochondrial respiration becomes constrained, promoting fermentation, despite available oxygen. This argues that cells engage in aerobic glycolysis when the demand for NAD+ is in excess of the demand for ATP.


Assuntos
Trifosfato de Adenosina/metabolismo , Glucose/metabolismo , Glicólise , NAD/metabolismo , Células A549 , Trifosfato de Adenosina/genética , Aerobiose , Glucose/genética , Células HeLa , Humanos , NAD/genética , Oxirredução
14.
Echocardiography ; 37(12): 2152-2154, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33107081

RESUMO

Vascular ring and sling are congenital anomalies of the vascular structure in the thorax with a prevalence of 2.4/10,000 live births. Double aortic arch (DAA), right aortic arch with left ductus arteriosus and aberrant left subclavian artery (RAA-ALSA), and pulmonary artery sling (PAS) are the three common types of vascular ring and sling. These anomalies can be isolated or accompanied by intracardiac malformation. The presence of both vascular ring and PAS is extremely rare. Here, we report a fetus who was prenatally diagnosed with PAS and RAA-ALS, and developed symptoms due to esophageal and airway compression after birth.


Assuntos
Canal Arterial , Anel Vascular , Aorta Torácica/diagnóstico por imagem , Canal Arterial/diagnóstico por imagem , Humanos , Estudos Retrospectivos
15.
Clin Lab ; 66(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902208

RESUMO

BACKGROUND: At present, the relationship between serum homocysteine and microalbuminuria (MAU) in systemic lupus erythematosus (SLE) patients is still unclear. Therefore, the aim of our study was to analyze the association between serum homocysteine and MAU in SLE patients. METHODS: The study analyzed 150 patients with SLE at Affiliated Hospital of Youjiang Medical University for Nationalities retrospectively, and we collected for clinical and laboratory data. RESULTS: We found a positive correlation between serum homocysteine and MAU in SLE patients (r = 0.430, p < 0.001). We found that serum homocysteine levels were increased in SLE patients with MAU positive compared to those who were MAU negative (p < 0.001). After adjusting for multiple confounding factors, we found that serum homocysteine maintained a positive correlation with MAU in patients with SLE in multivariate correlation analysis (p = 0.253, r = 0.002). The receiver operating characteristic (ROC) curve with an area under the curve of 0.730, and serum homocysteine had 72.2% sensitivity and 61.9% specificity with cutoff values 9.0 to identify the SLE patients with MAU positive. CONCLUSIONS: The current results found a correlation between serum homocysteine and MAU in SLE patients, suggesting that elevated serum homocysteine levels might be an adverse factor for SLE patients with kidney injury.


Assuntos
Lúpus Eritematoso Sistêmico , Albuminúria/diagnóstico , Homocisteína , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Curva ROC , Estudos Retrospectivos
16.
Cardiovasc Drugs Ther ; 34(1): 113-121, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32090295

RESUMO

Hydrogen sulfide (H2S), a novel gaseous signaling molecule, is a vital physiological signal in mammals. H2S protects the cardiovascular system via modulation of vasodilation, vascular remodeling, and inhibition of vascular calcification, and also has anti-atherosclerosis properties. Autophagy is a lysosomal-mediated intracellular degradation mechanism for excessive or abnormal proteins and lipids. The contribution of autophagy to normal and disease-state cell physiology is extremely complicated. Autophagy acts as a double-edged sword in the cardiovascular system. It can defend against damage to cells caused by environmental changes and it can also induce active cell death under certain conditions. In recent years, accumulating evidence indicates that H2S can up- or downregulate autophagy in many pathological processes, thereby switching from a harmful to a beneficial role. In this review, we summarize progress on understanding the mechanism by which H2S regulates autophagy in cardiovascular disease. We also discuss a H2S switch phenomenon that regulates autophagy and provides protection in cardiovascular diseases.


Assuntos
Autofagia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Sulfeto de Hidrogênio/metabolismo , Animais , Apoptose , Autofagia/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/patologia , Sistema Cardiovascular/fisiopatologia , Humanos , Sulfeto de Hidrogênio/uso terapêutico , Transdução de Sinais
17.
Sci Rep ; 9(1): 12141, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31413289

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

18.
Front Psychol ; 10: 1251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231278

RESUMO

Internet slang is a new language with innovative and novel characteristics, and its use can be considered a form of creative advertising. Embedding internet slang into advertisements can thus enhance their creative quality and increase the attention paid to them. In this study, we examined the effect of the characteristics of internet slang on attention to advertisements, brand awareness, product evaluation, and attitudes toward advertising by conducting two empirical studies, one utilizing eye-tracking experiments and the other utilizing questionnaires. We found that using internet slang in advertising significantly increased audience attention compared with standard language but did not necessarily improve product evaluation and brand awareness for various types of goods. We discovered code-switching effects of psycholinguistics existed in standard language and its variant (internet slang). Our findings can guide advertisers in selecting the embedded language that can be effective in achieving their desired advertising effect. Our findings also indicate that the excessive use of internet slang may have a negative effect on brand and product evaluation.

19.
Elife ; 82019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30990168

RESUMO

Cancer cell metabolism is heavily influenced by microenvironmental factors, including nutrient availability. Therefore, knowledge of microenvironmental nutrient levels is essential to understand tumor metabolism. To measure the extracellular nutrient levels available to tumors, we utilized quantitative metabolomics methods to measure the absolute concentrations of >118 metabolites in plasma and tumor interstitial fluid, the extracellular fluid that perfuses tumors. Comparison of nutrient levels in tumor interstitial fluid and plasma revealed that the nutrients available to tumors differ from those present in circulation. Further, by comparing interstitial fluid nutrient levels between autochthonous and transplant models of murine pancreatic and lung adenocarcinoma, we found that tumor type, anatomical location and animal diet affect local nutrient availability. These data provide a comprehensive characterization of the nutrients present in the tumor microenvironment of widely used models of lung and pancreatic cancer and identify factors that influence metabolite levels in tumors.


Assuntos
Líquido Extracelular/química , Neoplasias/patologia , Nutrientes/análise , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Feminino , Xenoenxertos/patologia , Masculino , Metabolômica , Camundongos Endogâmicos C57BL , Plasma/química
20.
World J Clin Cases ; 6(8): 183-191, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30148146

RESUMO

AIM: To assess the antiviral effects of hepatitis B virus (HBV) S gene-specific anti-gene locked nucleic acid (LNA) in transgenic mice. METHODS: Thirty HBV transgenic mice were acclimatized to laboratory conditions and positive for serum HBV surface antigen (HBsAg) and HBV DNA, were randomly divided into 5 groups (n = 7), including negative control (blank control, unrelated sequence control), positive control (lamivudine, anti-sense-LNA), and anti-gene-LNA experimental group. LNA was injected into transgenic mice by tail vein while lamivudine was administered by gavage. Serum HBV DNA and HBsAg levels were determined by fluorescence-based PCR and enzyme-linked immune sorbent assay, respectively. HBV S gene expression amounts were assessed by reverse transcription polymerase chain reaction. Positive rates of HBsAg in liver cells were evaluated immunohistochemistry. RESULTS: Average rate reductions of HBsAg after treatment on the 3rd, 5th, and 7th days were 32.34%, 45.96%, and 59.15%, respectively. The inhibitory effect of anti-gene-LNA on serum HBsAg peaked on day 7, with statistically significant differences compared with pre-treatment (0.96 ± 0.18 vs 2.35 ± 0.33, P < 0.05) and control values (P < 0.05 for all). Average reduction rates of HBV DNA on the 3rd, 5th, and 7th days were 38.55%, 50.95%, and 62.26%, respectively. This inhibitory effect peaked on the 7th day after treatment with anti-gene-LNA, with statistically significant differences compared with pre-treatment (4.17 ± 1.29 vs 11.05 ± 1.25, P < 0.05) and control values (P < 0.05 for all). The mRNA levels of the HBV S gene (P < 0.05 for all) and rates of HBsAg positive liver cells (P < 0.05 for all) were significantly reduced compared with the control groups. Liver and kidney function, and histology showed no abnormalities. CONCLUSION: Anti-gene-LNA targeting the S gene of HBV displays strong inhibitory effects on HBV in transgenic mice, providing theoretical and experimental bases for gene therapy in HBV.

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