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1.
PLoS One ; 18(11): e0294322, 2023.
Article in English | MEDLINE | ID: mdl-37976248

ABSTRACT

Chronic methamphetamine use, a widespread drug epidemic, has been associated with cardiac morphological and electrical remodeling, leading to the development of numerous cardiovascular diseases. While methamphetamine has been documented to induce arrhythmia, most results originate from clinical trials from users who experienced different durations of methamphetamine abuse, providing no documentation on the use of methamphetamine in standardized settings. Additionally, the underlying molecular mechanism on how methamphetamine affects the cardiovascular system remains elusive. A relationship was sought between cardiotoxicity and arrhythmia with associated methamphetamine abuse in zebrafish to identify and to understand the adverse cardiac symptoms associated with methamphetamine. Zebrafish were first treated with methamphetamine 3 times a week over a 2-week duration. Immediately after treatment, zebrafish underwent electrocardiogram (ECG) measurement using an in-house developed acquisition system for electrophysiological analysis. Subsequent analyses of cAMP expression and Ca2+ regulation in zebrafish cardiomyocytes were conducted. cAMP is vital to development of myocardial fibrosis and arrhythmia, prominent symptoms in the development of cardiovascular diseases. Ca2+ dysregulation is also a factor in inducing arrhythmias. During the first week of treatment, zebrafish that were administered with methamphetamine displayed a decrease in heart rate, which persisted throughout the second week and remained significantly lower than the heart rate of untreated fish. Results also indicate an increased heart rate variability during the early stage of treatment followed by a decrease in the late stage for methamphetamine-treated fish over the duration of the experiment, suggesting a biphasic response to methamphetamine exposure. Methamphetamine-treated fish also exhibited reduced QTc intervals throughout the experiment. Results from the cAMP and Ca2+ assays demonstrate that cAMP was upregulated and Ca2+ was dysregulated in response to methamphetamine treatment. Collagenic assays indicated significant fibrotic response to methamphetamine treatment. These results provide potential insight into the role of methamphetamine in the development of fibrosis and arrhythmia due to downstream effectors of cAMP.


Subject(s)
Cardiovascular Diseases , Methamphetamine , Animals , Methamphetamine/toxicity , Zebrafish , Cardiovascular Diseases/chemically induced , Calcium/therapeutic use , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/drug therapy
2.
Elife ; 112022 Oct 18.
Article in English | MEDLINE | ID: mdl-36255053

ABSTRACT

Previously we showed the generation of a protein trap library made with the gene-break transposon (GBT) in zebrafish (Danio rerio) that could be used to facilitate novel functional genome annotation towards understanding molecular underpinnings of human diseases (Ichino et al, 2020). Here, we report a significant application of this library for discovering essential genes for heart rhythm disorders such as sick sinus syndrome (SSS). SSS is a group of heart rhythm disorders caused by malfunction of the sinus node, the heart's primary pacemaker. Partially owing to its aging-associated phenotypic manifestation and low expressivity, molecular mechanisms of SSS remain difficult to decipher. From 609 GBT lines screened, we generated a collection of 35 zebrafish insertional cardiac (ZIC) mutants in which each mutant traps a gene with cardiac expression. We further employed electrocardiographic measurements to screen these 35 ZIC lines and identified three GBT mutants with SSS-like phenotypes. More detailed functional studies on one of the arrhythmogenic mutants, GBT411, in both zebrafish and mouse models unveiled Dnajb6 as a novel SSS causative gene with a unique expression pattern within the subpopulation of sinus node pacemaker cells that partially overlaps with the expression of hyperpolarization activated cyclic nucleotide gated channel 4 (HCN4), supporting heterogeneity of the cardiac pacemaker cells.


Subject(s)
Sick Sinus Syndrome , Zebrafish , Mice , Animals , Humans , Sick Sinus Syndrome/genetics , Zebrafish/genetics , Zebrafish/metabolism , Sinoatrial Node/metabolism , Phenotype , Electrocardiography/adverse effects , Arrhythmias, Cardiac/metabolism , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism , Nerve Tissue Proteins/metabolism , Molecular Chaperones/metabolism , HSP40 Heat-Shock Proteins/genetics
3.
Biosens Bioelectron ; 210: 114292, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35490628

ABSTRACT

Simultaneous monitoring of electrocardiogram (ECG) and electroencephalogram (EEG) in studied animal models requires innovative engineering techniques that can capture minute physiological changes. However, this is often administered with a bulky and/or invasive system that may cause discomfort to animals and signal distortions. Here, we develop an integrated bioelectronic sensing system to provide simultaneous recordings of ECG and EEG in real-time for Xenopus laevis. The microelectrode array (MEA) membrane and the distinct anatomy of Xenopus offer noninvasive multi-modal electrophysiological monitoring with favorable spatial resolution. The system was validated under different environmental conditions, including drug exposure and temperature changes. Under the exposure of Pentylenetetrazol (PTZ), an epilepsy-inducing drug, clear ECG and EEG alterations, including frequent ictal and interictal EEG events, 30 dB average EEG amplitude elevations, abnormal ECG morphology, and heart rate changes, were observed. Furthermore, the ECG and EEG were monitored and analyzed under different temperatures. A decrease in relative power of delta band was observed when cold environment was brought about, in contrast to an increase in relative power of other higher frequency bands while the ECG remained stable. Overall, the real-time electrophysiology monitoring system using the Xenopus model holds potential for many applications in drug screening and remote environmental monitoring.


Subject(s)
Biosensing Techniques , Animals , Electrocardiography/methods , Electroencephalography/methods , Heart , Microelectrodes , Xenopus laevis
4.
Sensors (Basel) ; 22(7)2022 Apr 05.
Article in English | MEDLINE | ID: mdl-35408402

ABSTRACT

Fetal electrocardiogram (fECG) assessment is essential throughout pregnancy to monitor the wellbeing and development of the fetus, and to possibly diagnose potential congenital heart defects. Due to the high noise incorporated in the abdominal ECG (aECG) signals, the extraction of fECG has been challenging. And it is even a lot more difficult for fECG extraction if only one channel of aECG is provided, i.e., in a compact patch device. In this paper, we propose a novel algorithm based on the Ensemble Kalman filter (EnKF) for non-invasive fECG extraction from a single-channel aECG signal. To assess the performance of the proposed algorithm, we used our own clinical data, obtained from a pilot study with 10 subjects each of 20 min recording, and data from the PhysioNet 2013 Challenge bank with labeled QRS complex annotations. The proposed methodology shows the average positive predictive value (PPV) of 97.59%, sensitivity (SE) of 96.91%, and F1-score of 97.25% from the PhysioNet 2013 Challenge bank. Our results also indicate that the proposed algorithm is reliable and effective, and it outperforms the recently proposed extended Kalman filter (EKF) based algorithm.


Subject(s)
Mothers , Signal Processing, Computer-Assisted , Algorithms , Arrhythmias, Cardiac , Electrocardiography/methods , Female , Fetal Monitoring/methods , Fetus , Humans , Pilot Projects , Pregnancy
5.
IEEE Sens Lett ; 6(9)2022 Sep.
Article in English | MEDLINE | ID: mdl-37637479

ABSTRACT

Fetal heart rate (fHR) is an important indicator for monitoring of fetal cardiac health and development. The widely-used method based on ultrasound, however, is not continuous and often requires an expert to perform; thus, it is mostly used in clinics during checkups. The advances in wearable technology have paved the way for home assessment of fHR via the extraction of the mother's abdominal electrocardiogram (ECG) acquired by novel patches. Several methods have been developed for such; however, the computation is either too slow for real-time monitoring or too heavy to be performed in a wearable. In this work, we develop and validate the Lullaby algorithm - a novel method for fetal QRS extraction from aECG. The results showed that Lullaby is almost 7 times faster than existing methods with a better F1-score of 0.815, holding promise to transform perinatal monitoring.

6.
Biosens Bioelectron ; 197: 113808, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34801796

ABSTRACT

Zebrafish and their mutant lines have been extensively used in cardiovascular studies. In the current study, the novel system, Zebra II, is presented for prolonged electrocardiogram (ECG) acquisition and analysis for multiple zebrafish within controllable working environments. The Zebra II is composed of a perfusion system, apparatuses, sensors, and an in-house electronic system. First, the Zebra II is validated in comparison with a benchmark system, namely iWORX, through various experiments. The validation displayed comparable results in terms of data quality and ECG changes in response to drug treatment. The effects of anesthetic drugs and temperature variation on zebrafish ECG were subsequently investigated in experiments that need real-time data assessment. The Zebra II's capability of continuous anesthetic administration enabled prolonged ECG acquisition up to 1 h compared to that of 5 min in existing systems. The novel, cloud-based, automated analysis with data obtained from four fish further provided a useful solution for combinatorial experiments and helped save significant time and effort. The system showed robust ECG acquisition and analytics for various applications including arrhythmia in sodium induced sinus arrest, temperature-induced heart rate variation, and drug-induced arrhythmia in Tg(SCN5A-D1275N) mutant and wildtype fish. The multiple channel acquisition also enabled the implementation of randomized controlled trials on zebrafish models. The developed ECG system holds promise and solves current drawbacks in order to greatly accelerate drug screening applications and other cardiovascular studies using zebrafish.


Subject(s)
Biosensing Techniques , Heart Diseases , Animals , Drug Evaluation, Preclinical , Electrocardiography , Zebrafish
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 7116-7119, 2021 11.
Article in English | MEDLINE | ID: mdl-34892741

ABSTRACT

We develop a novel wearable fetal electrocardiogram (fECG) monitoring system consisting of an abdominal patch that communicates with a smart device. The system has two main components: the fetal patch and the monitoring app. The fetal patch has electronics and recording electrodes fabricated on a hybrid flexible-rigid platform while the Android app is developed for a wide range of applications. The patch collects the abdominal ECG (aECG) signals that are sent to the smart device app via secure Bluetooth Low Energy (BLE) communication. The app software connects to a cloud server where processing and extraction algorithms are executed for real-time fECG extraction and fetal heartrate (fHR) calculation from the collected raw data. We have validated the algorithms and real-time data recordings on pregnant subjects yielding promising results. Our system has the potential to transform the currently used fetal monitoring system to an effective distanced and telematernity care.


Subject(s)
Fetal Monitoring , Signal Processing, Computer-Assisted , Algorithms , Electrocardiography , Female , Heart Rate, Fetal , Humans , Pregnancy
8.
Int J Biol Sci ; 17(1): 259-270, 2021.
Article in English | MEDLINE | ID: mdl-33390848

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) causes aggressive and lethal malignancies with extremely poor prognoses, and accounts for about 90% of cases of esophageal cancer. Neuropilin and tolloid-like 2 (NETO2) protein coding genes have been associated with various human cancers. Nevertheless, little information is reported about the phenotypic expression and its clinical significance in ESCC progression. Here, our study found that NETO2 expression in ESCC patients was associated with tumor clinical stage and lymph node metastasis status. Gain-of-function and loss-of-function analyses showed that NETO2 stimulated ESCC cell proliferation while suppressing apoptosis in vitro and enhanced tumor growth in vivo. Moreover, knockdown of NETO2 significantly inhibited migration and invasion in combination with regulation of epithelial-mesenchymal transition (EMT) related markers. Mechanistically, overexpression of NETO2 increased the phosphorylation of ERK, PI3k/AKT, and Nuclear factor erythroid-2-related factor 2(Nrf2), whereas silencing NETO2 decreased the phosphorylation of these targets. Our data suggest that Nrf2 was a critical downstream event responsible for triggering the PI3K/AKT and ERK signaling pathways and plays a crucial role in NETO2-mediated tumorigenesis. Taken together, NETO2 acts as an oncogene and might serve as a novel therapeutic target or prognostic biomarker in ESCC patients.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Esophageal Neoplasms/metabolism , Membrane Proteins/metabolism , NF-E2-Related Factor 2/metabolism , Carcinoma, Squamous Cell/diagnosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Epithelial-Mesenchymal Transition , Esophageal Neoplasms/diagnosis , Female , Humans , MAP Kinase Signaling System , Male , Middle Aged , Neoplasm Metastasis , Phosphatidylinositol 3-Kinases/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolism
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2610-2613, 2020 07.
Article in English | MEDLINE | ID: mdl-33018541

ABSTRACT

The zebrafish model has been demonstrated as an ideal vertebrate model system for a diverse range of biological studies. Along with conventional approaches, monitoring and analysis of zebrafish electrocardiogram (ECG) have been utilized for cardio-physiological screening and elucidation. ECG monitoring has been carried out with fish treated with anesthetic drugs, rendering the short period of time in recording the signals (<5 min). In this work, a prolonged sedation system for continuous ECG monitoring of multiple zebrafish was proposed and developed. We built a circulation system to provide prolonged mild anesthesia which allows more consistent and intrinsic ECG measurement. The use of prolonged anesthesia helped reduce the concentration of the anesthetic drug (MS222 or Tricaine) from 200 mg/L to 100 mg/L and even lower; thus, maintaining the integrity of intrinsic ECG. Moreover, heartrate variation during recording was investigated, showing minute changes (±3.2 beats per minute - BPM). The development of this prolonged ECG monitoring system would open the possibility of long-term monitoring for studies such as drug screening and forward genetic screening.


Subject(s)
Anesthesia , Anesthesiology , Animals , Electrocardiography , Heart Rate , Zebrafish
10.
Sensors (Basel) ; 20(13)2020 Jul 04.
Article in English | MEDLINE | ID: mdl-32635568

ABSTRACT

The invasive method of fetal electrocardiogram (fECG) monitoring is widely used with electrodes directly attached to the fetal scalp. There are potential risks such as infection and, thus, it is usually carried out during labor in rare cases. Recent advances in electronics and technologies have enabled fECG monitoring from the early stages of pregnancy through fECG extraction from the combined fetal/maternal ECG (f/mECG) signal recorded non-invasively in the abdominal area of the mother. However, cumbersome algorithms that require the reference maternal ECG as well as heavy feature crafting makes out-of-clinics fECG monitoring in daily life not yet feasible. To address these challenges, we proposed a pure end-to-end deep learning model to detect fetal QRS complexes (i.e., the main spikes observed on a fetal ECG waveform). Additionally, the model has the residual network (ResNet) architecture that adopts the novel 1-D octave convolution (OctConv) for learning multiple temporal frequency features, which in turn reduce memory and computational cost. Importantly, the model is capable of highlighting the contribution of regions that are more prominent for the detection. To evaluate our approach, data from the PhysioNet 2013 Challenge with labeled QRS complex annotations were used in the original form, and the data were then modified with Gaussian and motion noise, mimicking real-world scenarios. The model can achieve a F1 score of 91.1% while being able to save more than 50% computing cost with less than 2% performance degradation, demonstrating the effectiveness of our method.


Subject(s)
Deep Learning , Electrocardiography , Fetal Monitoring , Signal Processing, Computer-Assisted , Algorithms , Female , Humans , Pregnancy
11.
PLoS One ; 15(5): e0232457, 2020.
Article in English | MEDLINE | ID: mdl-32401822

ABSTRACT

Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of ~100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.


Subject(s)
Aging/genetics , Aging/physiology , Sick Sinus Syndrome/etiology , Sinus Arrest, Cardiac/etiology , Zebrafish/genetics , Zebrafish/physiology , Animals , Animals, Genetically Modified , Disease Models, Animal , Electrocardiography , Humans , Mice , Models, Cardiovascular , Mutation, Missense , NAV1.5 Voltage-Gated Sodium Channel/genetics , Sick Sinus Syndrome/genetics , Sick Sinus Syndrome/physiopathology , Sinus Arrest, Cardiac/genetics , Sinus Arrest, Cardiac/physiopathology , Species Specificity , Zebrafish Proteins/genetics
12.
J Adolesc Health ; 67(3): 392-400, 2020 09.
Article in English | MEDLINE | ID: mdl-32317207

ABSTRACT

PURPOSE: Schools provide access to mental health services for traditionally underserved youth. However, there is variability in the types of school-based services students receive (e.g., school counseling, services in separate classrooms, or schools serving students with psychiatric disorders). Prior research has typically not distinguished among these different types of school-based services. The present study examines sociodemographic characteristics and disorders associated with the types of services received in schools. METHODS: Data were analyzed from a sample of adolescent-parent pairs in the U.S. National Comorbidity Survey Adolescent Supplement who received school mental health services (N = 1,204). DSM-IV diagnoses were based on the Composite International Diagnostic Interview administered to adolescents and questionnaires self-administered to parents. Adolescents (aged 13-18 years) and parents also responded to questions about lifetime school-based mental health service receipt. RESULTS: Among those receiving school-based mental health services, almost one-third (29.7%) received services in a separate classroom and almost one-fourth (22.3%) in a separate school. Increased likelihood of lifetime placement in a separate classroom or school was detected among older youth, males, blacks, Latinos, youth with learning disabilities, those whose parents had fewer years of education, and those who received community-based mental health services. Oppositional defiant disorder was associated with increased lifetime placement in a separate school. CONCLUSIONS: The results advance the evidence base by indicating that racial/ethnic minority youth and those whose parents have fewer years of education were more likely to receive school-based mental health services in separate settings. These results provide more context to studies of school-based mental health service receipt.


Subject(s)
Mental Disorders , Mental Health Services , School Mental Health Services , Adolescent , Ethnicity , Humans , Male , Mental Disorders/epidemiology , Mental Disorders/therapy , Minority Groups
13.
Technologies (Basel) ; 8(2)2020 Jun.
Article in English | MEDLINE | ID: mdl-34277367

ABSTRACT

Monitoring of fetal electrocardiogram (fECG) would provide useful information about fetal wellbeing as well as any abnormal development during pregnancy. Recent advances in flexible electronics and wearable technologies have enabled compact devices to acquire personal physiological signals in the home setting, including those of expectant mothers. However, the high noise level in the daily life renders long-entrenched challenges to extract fECG from the combined fetal/maternal ECG signal recorded in the abdominal area of the mother. Thus, an efficient fECG extraction scheme is a dire need. In this work, we intensively explored various extraction algorithms, including template subtraction (TS), independent component analysis (ICA), and extended Kalman filter (EKF) using the data from the PhysioNet 2013 Challenge. Furthermore, the modified data with Gaussian and motion noise added, mimicking a practical scenario, were utilized to examine the performance of algorithms. Finally, we combined different algorithms together, yielding promising results, with the best performance in the F1 score of 92.61% achieved by an algorithm combining ICA and TS. With the data modified by adding different types of noise, the combination of ICA-TS-ICA showed the highest F1 score of 85.4%. It should be noted that these combined approaches required higher computational complexity, including execution time and allocated memory compared with other methods. Owing to comprehensive examination through various evaluation metrics in different extraction algorithms, this study provides insights into the implementation and operation of state-of-the-art fetal and maternal monitoring systems in the era of mobile health.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-873138

ABSTRACT

" Basaga" is one of the commonly used medicinal materials in Mongolian medicine. It has a long history and effects in cooling blood, stopping stabbing pain and detoxifying. The " Basaga" in Mongolian medicine compound preparations have been widely used in various Mongolian hospitals because of its remarkable clinical efficacy. However, due to the differences in inheritance, medicinal parts and plants in Inner Mongolia, the phenomena of homonym and synonym in the application of " Basaga" have been very obvious, which leads to confusion in clinical use, and challenges the safety and effectiveness of this kind of Mongolian medicine. To understand the application of " Basaga" in Mongolian medicine compound preparation, and collect and summarize the types of " Basaga" preparations and the variety of " Basaga" used in preparations and formulations, functional indications and clinical applications were analyzed and collected based on standards and specifications of Mongolian medicine, the application of Mongolian medicine hospitals and Mongolian medicine hospital' s preparation room in Inner Mongolian, and relevant documents in recent years were reviewed. The data can provide references for optimizing and improving " Basaga" , Mongolian medicine standards and the overall standard level. What' s more, the basic data for strengthening the comprehensive development and research of " Basaga" in Mongolian medicine compound preparations in future, so as to ensure and improve the accuracy and clinical effectiveness of " Basaga" in prescriptions of Mongolian patent medicine, and lay a foundation for rational use and modern research of " Basaga" Mongolian medicine.

15.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3162-3169, 2019 Aug.
Article in Chinese | MEDLINE | ID: mdl-31602868

ABSTRACT

This paper investigates and counts the ethnic medicines of the Ewenki,Daur and Oroqen ethnic groups,which are known as the " Three Minorities" in Inner Mongolia. Through the methods of literature collection,interview investigation,and resource investigation,different ethnic medicines were collected on the main diseases,drug varieties,drug-injection sites,and drug administration methods. Through data statistics and SPSS analysis,the similarities and individual differences between the three ethnic groups were clarified. The results indicated the predicament of the current national medicine,which is helpful for the protection and inheritance of ethnic medicine.


Subject(s)
Ethnicity , Ethnopharmacology , China , Humans , Mongolia
16.
J Mol Cell Cardiol ; 133: 199-208, 2019 08.
Article in English | MEDLINE | ID: mdl-31228518

ABSTRACT

Adult zebrafish is an emerging vertebrate model for studying genetic basis of cardiomyopathies; but whether the simple fish heart can model essential features of hypertrophic cardiomyopathy (HCM) remained unknown. Here, we report a comprehensive phenotyping of a lamp2 knockout (KO) mutant. LAMP2 encodes a lysosomal protein and is a causative gene of Danon disease that is characterized by HCM and massive autophagic vacuoles accumulation in the tissues. There is no effective therapy yet to treat this most lethal cardiomyopathy in the young. First, we did find the autophagic vacuoles accumulation in cardiac tissues from lamp2 KO. Next, through employing a set of emerging phenotyping tools, we revealed heart failure phenotypes in the lamp2 KO mutants, including decreased ventricular ejection fraction, reduced physical exercise capacity, blunted ß-adrenergic contractile response, and enlarged atrium. We also noted changes of the following indices suggesting cardiac hypertrophic remodeling in lamp2 KO: a rounded heart shape, increased end-systolic ventricular volume and density of ventricular myocardium, elevated actomyosin activation kinetics together with increased maximal isometric tension at the level of cardiac myofibrils. Lastly, we assessed the function of lysosomal-localized mTOR on the lamp2-associated Danon disease. We found that haploinsufficiency of mtor was able to normalize some characteristics of the lamp2 KO, including ejection fraction, ß-adrenergic response, and the actomyosin activation kinetics. In summary, we demonstrate the feasibility of modeling the inherited HCM in the adult zebrafish, which can be used to develop potential therapies.


Subject(s)
Glycogen Storage Disease Type IIb/metabolism , Lysosomal-Associated Membrane Protein 2/genetics , Phenotype , TOR Serine-Threonine Kinases/antagonists & inhibitors , Zebrafish/genetics , Animals , Cardiomegaly/genetics , Disease Models, Animal , Gene Knockout Techniques , Glycogen Storage Disease Type IIb/genetics , Lysosomal-Associated Membrane Protein 2/metabolism , Myocardial Contraction/genetics , Myocardium/metabolism , Myofibrils/metabolism , Receptors, Adrenergic, beta/metabolism , Stroke Volume , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Ventricular Remodeling/genetics , Zebrafish/metabolism
17.
Biomed Res Int ; 2019: 2692970, 2019.
Article in English | MEDLINE | ID: mdl-30800665

ABSTRACT

In previous studies, Gentianella acuta (Michx.) Hulten was reported to contain xanthones, iridoids, terpenoids, and sterols and is mainly used to cure hepatitis, jaundice, fever, headache, and angina pectoris. In this study, we used bioassay guided fractionation to identify compounds from G. acuta and investigated their activity against hydrogen peroxide (H2O2)-induced apoptosis of H9c2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic (GCLC) expression were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated using western blot. The results showed that all four compounds had protective effects on H9c2 cells. The transcription levels of HO-1 and GCLC significantly increased in H9c2 cells pretreated with norswertianolin (1), swetrianolin (2), demethylbellidifolin (3), and bellidifolin (4). However, compared to the model group, the transcription levels of Nrf2 were not enhanced by pretreatment with compounds 1, 2, and 4. The protein expression levels of HO-1 and GCLC in H9c2 cells were greater than that in the H2O2-treated group, and the expression of Nrf2 was not significantly changed except by swetrianolin treatment; inhibitors can reverse the protective effect by ZnPP (15 µM), BSO (10 µM), and brusatol (10 µM). The results indicated that the four compounds isolated from G. acuta inhibited the oxidative injury induced by H2O2 by activating the Nrf2/ARE pathway in H9c2 cells and provide evidence that G. acuta may be a potential therapeutic agent for the treatment of cardiovascular diseases.


Subject(s)
Gentianella/chemistry , Hydrogen Peroxide/pharmacology , Plant Extracts/pharmacology , Protective Agents/pharmacology , Animals , Apoptosis/drug effects , Cell Line , Glutamate-Cysteine Ligase/metabolism , Heme Oxygenase-1/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Rats , Transcription, Genetic/drug effects , Xanthenes/pharmacology , Xanthones/pharmacology
18.
JMIR Res Protoc ; 8(1): e2, 2019 Jan 31.
Article in English | MEDLINE | ID: mdl-30702440

ABSTRACT

BACKGROUND: Having mobile devices that provide patients with the ability to record and monitor the electrical activity of their heart enhances patient self-care and the early detection of irregular heartbeat (cardiac arrhythmia), yet few such devices exist in Vietnam. Challenges exist for introducing mobile electrocardiography (ECG) monitoring devices in Vietnam, including patient accessibility and affordability. A low-cost mobile ECG monitoring device designed and developed in Vietnam, which allows patients to easily measure their heart's electrical activity and navigate recordings, may be a solution. OBJECTIVE: The aim of this project is to assess the usability of the MD-Link system, a newly developed mobile handheld 1-lead ECG device, in detecting patients with irregular heartbeat. We will compare its outputs to the standard printed outputs of a 12-lead electrocardiogram generated by the Nihon Kohden Cardiofax S Electrocardiograph Model ECG-1250K. METHODS: We will conduct a cross-sectional study in two stages, including the measurement of ECG signals of patients using the MD-Link and the Nihon Kohden Cardiofax S and analysis of the selected standard outputs collected from the ECG recordings of the MD-Link and the Nihon Kohden Cardiofax S. The MD-Link consists of (1) a mobile device (eg, a smartphone); (2) a lead wire with 2 disposable electrodes; and (3) an easy-to-use mobile app interface enabling the upload and accurate display of ECG recordings to patients and their clinicians. Our research team, consisting of members from Dartmouth College; the Institute of Health, Population and Development; Hanoi University of Science and Technology; and physicians and nurses from Thanh Chan Clinic, will assist in carrying out this project. RESULTS: We will proceed with a publication plan that includes a project report and, ultimately, articles for peer-reviewed journals. We also hope to disseminate our work at relevant conferences to provide more coverage and exposure to the MD-Link mobile device. Recruitment and data collection were completed in January 2018. Data analysis started in February 2018 and is ongoing. Results are expected mid-2019. CONCLUSIONS: At the end of this project, we will have developed and tested the MD-Link, a low-cost mobile ECG monitoring device, with some supportive comparisons to standard ECG devices commonly used in heart clinics or hospitals in Vietnam. Our long-term goal is for the MD-Link to be easily accessible, affordable, and to fit into a patient's daily routine, thus improving the care and treatment of patients with cardiovascular diseases (CVDs). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/8762.

19.
Article in English | MEDLINE | ID: mdl-34622249

ABSTRACT

Electrocardiogram (ECG) monitoring of the fetus during pregnancy, before and during labor, can provide crucial information for the assessment of fetal well-being and development, as well as labor progress. An out-of-clinics fetal ECG monitoring system may pave the way for instant diagnosis, suggesting immediate intervention, which could help reduce the fetal mortality rate. In this paper, we present an unobtrusive fetal maternal ECG monitoring system which can operate in the home setting. The acquisition of the mother's abdominal ECG is done using the non-contact electrode approach. The extraction of the fetal ECG from the combined fetal/maternal ECG signal is investigated using both Fast Independent Component Analysis (FastICA) and RobustICA algorithms. An accelerometer is integrated for motion artifact detection which would help reduce interferences due to movement. The device also is connected to a cloud server, allowing doctors to access the data in real time.

20.
IEEE Sens J ; 19(11): 4283-4289, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-32855627

ABSTRACT

Long-term monitoring of intrinsic electrocardiogram (ECG) in zebrafish plays a crucial role in heart disease studies as well as drug screening. In this work, we developed a polymer-based apparatus with embedded flexible thin-film electrodes to acquire ECG signals of awake zebrafish. The apparatus was made of polydimethylsiloxane (PDMS) using the molding technique with molds formed by 3D printing. A graphical user interface (GUI) was built in National Instruments LabView platform for real-time recording, processing and analysis. The program provided important features, such as signal de-noising, characteristic wave detection and anomaly detection. Further, it could operate on both real-time coming signals as well as previously-saved data, facilitating analysis and interpretation. We demonstrated the use of our system to investigate the effects of the anesthetic drug, namely Tricaine (MS-222), on cardiac electrophysiology of zebrafish, revealing promising findings. We speculate that our novel system may contribute to a host of studies in various disciplines using the zebrafish model.

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