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1.
STOMATOLOGY ; (12): 217-221, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-979357

ABSTRACT

Objective@#To investigate the efficacy of different bleaching methods on white-spot lesions of the enamel using optical coherence tomography and to evaluate its feasibility for monitoring the therapeutic effects on white-spot lesions. @*Methods@#Forty-eight sound premolars extracted for orthodontic reasons were selected and cut for 4 mm×4 mm×2 mm enamel blocks in buccal surfaces of the crowns. The samples were covered with acid-resistant varnish (except for the buccal surfaces) and immersed in demineralization solution for 18 days to establish the white-spot lesion models of the enamels. Samples were randomly divided into four groups (n=12). Group A was given demineralization only. Specimens in Group B, C and D were treated with 40% hydrogen peroxide, resin infiltration and 40% hydrogen peroxide combined with resin infiltration, respectively. Eight samples in each group were randomly selected. OCT was applied to observe the optical changes of the enamel surface and according to the OCT scanning results, the demineralization depth of enamel samples in each group was calculated. Then, the enamel blocks were embedded in epoxy resins, except the buccal surfaces, and measured for the microhardness values of the enamel surface by a microindentation hardness tester. Four samples in each group were cut longitudinally, and the ultrastructural changes of enamel samples in each group were observed by scanning electron microscope. @* Results@#OCT showed that the light scattering characteristics of enamel surface changed in all groups, and the bright layer was formed, but the thickness of bright layer in Group C and D was significantly lower than that in Group A and B (P<0.05). The microhardness values (kg/mm2) of the samples in Group A-D were (214.99±31.70), (250.66±33.64), (312.42±18.01) and(286.53±26.65), respectively. The microhardness of enamel surfaces in Group C and D was significantly higher than that in Group A and B (P<0.05), and the ultrastructure of enamel surfaces in Group C and D were more flat and dense in SEM observation (P<0.05). @*Conclusion@#The methods of resin infiltration therapy or 40% hydrogen peroxide combined with resin infiltration could effectively improve white-spot lesions of the enamel and the non-invasive OCT can be used as a better evaluation method for the diagnosis and treatment of white-spot lesions of the enamel.

2.
Folia Neuropathol ; 59(4): 359-371, 2021.
Article in English | MEDLINE | ID: mdl-35114776

ABSTRACT

INTRODUCTION: Gliomas are the most seen tumours in adults in the central nervous system, and high grade of gliomas cause the worse prognose of patients with a shorter survival period. Ubiquitin-specific protease 38 (USP38) has been regarded as the negative regulator of type I interferon signalling; it regulates the ubiquitination process of TANK binding kinase 1 (TBK1). Further study revealed that USP38 also stabilizes the protein lysine-specific histone demethylase 1A (LSD1) via cleaving the ubiquitin chain. However, the effect of USP38 in colorectal cancer was not fully understood. MATERIAL AND METHODS: USP38 overexpression and knockdown vector were constructed using the molecular clone method. The viability rate of U-87MG and U-138MG cells were detected using the Cell Counting Kit-8 (CCK-8) method.The expression and secretion of metastasis-related molecules were detected using the qPCR and ELISA method. The expression of metastasis-related molecules and JAK2/STAT3 signalling pathway was detected using western blotting analysis. RESULTS: In this study, we firstly constructed a USP38 overexpression and inhibition model in 2 cell lines and found that overexpression of USP38 inhibits the viability rate and migration ability of glioma cells. We further noticed that elevated expression of USP38 reduced the expression and secretion of cell adhesion-related molecules with the elevation in expression of pro-apoptotic proteins, and these effects might be mediated by inhibition of JAK2/STAT3 signalling pathway as USP38 is the upstream regulator of STAT3 and inhibition of cellular adhesion process. CONCLUSIONS: USP38 might be a new therapeutic target for glioma.


Subject(s)
Glioma , Ubiquitin-Specific Proteases , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Glioma/genetics , Humans , Janus Kinase 2 , Neoplasm Metastasis , STAT3 Transcription Factor/metabolism , Signal Transduction , Ubiquitin-Specific Proteases/genetics , Ubiquitin-Specific Proteases/metabolism , Ubiquitination
3.
Polymers (Basel) ; 12(10)2020 Oct 01.
Article in English | MEDLINE | ID: mdl-33019778

ABSTRACT

Currently, controlled release formulations (CRFs) of pesticides in response to biotic and/or abiotic stimuli have shown great potential for providing "on-demand" smart release of loaded active ingredients. In this study, amphiphilic biopolymers were prepared by introducing hydrophobic (7-diethylaminocoumarin-4-yl)methyl succinate (DEACMS) onto the main chain of hydrophilic carboxymethylchitosan (CMCS) via the formation of amide bonds which were able to self-assemble into spherical micelles in aqueous media and were utilized as light-responsive nanocarriers for the controlled release of pesticides. FTIR and NMR characterizations confirmed the successful synthesis of the CMCS-DEACMS conjugate. The critical micelle concentration (CMC) decreased with the increase in the substitution of DEACMS on CMCS, which ranged from 0.013 to 0.042 mg/mL. Upon irradiation under simulated sunlight, the hydrodynamic diameter, morphology, photophysical properties and photolysis were researched by means of dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-vis absorption spectroscopy and fluorescence spectroscopy. Moreover, 2,4-dichlorophenoxyacetic acid (2,4-D) was used as a model pesticide and encapsulated into the CMCS-DEACMS micelles. In these micelle formulations, the release of 2,4-D was promoted upon simulated sunlight irradiation, during which the coumarin moieties were cleaved from the CMCS backbone, resulting in a shift of the hydrophilic-hydrophobic balance and destabilization of the micelles. Additionally, bioassay studies suggested that this 2,4-D contained which micelles showed good bioactivity on the target plant without harming the nontarget plant. Thereby, the light-responsive CMCS-DEACMS micelles bearing photocleavable coumarin moieties provide a smart delivery platform for agrochemicals.

4.
Vaccines (Basel) ; 8(2)2020 Jun 26.
Article in English | MEDLINE | ID: mdl-32604831

ABSTRACT

Porcine circovirus-associated diseases (PCVADs) cause considerable economic losses in industrial pork production in the field. To minimize the economic losses due to PCVAD, porcine circovirus type 2 (PCV2) vaccines have been developed, and there is widespread vaccination worldwide today. However, limited information is available concerning the current status of PCV2 infection in the field on the Asian continent. The present study aimed to assess sero- and viral dynamics of PCV2 from 12 PCV2-contaminated pig herds with vaccination against PCV2 in Southern and Central Taiwan. In particular, the level of PCV2 load during the window period for seroconversion using real-time polymerase chain reaction and a commercial enzyme-linked immunosorbent assay (ELISA) kit. Our results revealed that pig herds showed slight or no seroconversion after three to four weeks post-PCV2 immunization. The presence of PCV2 was observed during the window period for seroconversion in all herds. In conclusion, natural exposure of PCV2 occurs in the growing to fattening period, and viremia can last until slaughter. Additionally, our findings indicate that using ELISA showed the level of antibodies and aided in the understanding and surveillance of the current PCV2 status in the field.

5.
Cancer Res ; 76(23): 6816-6827, 2016 12 01.
Article in English | MEDLINE | ID: mdl-27760789

ABSTRACT

Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45+ bone marrow-derived cells. Subsequent long-term conditioning of naïve mice with exosomes from highly metastatic breast cancer cells revealed the accumulation of myeloid-derived suppressor cells in the lung and liver. This favorable immune suppressive microenvironment was capable of promoting metastatic colonization in the lung and liver, an effect not observed from exosomes derived from nonmetastatic cells and liposome control vesicles. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation and inhibited NK cell cytotoxicity, and hence likely suppressed the anticancer immune response in premetastatic organs. Together, our findings provide novel insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to immune suppression and promotion of metastases. Cancer Res; 76(23); 6816-27. ©2016 AACR.


Subject(s)
Breast Neoplasms/immunology , Exosomes/metabolism , Immunosuppression Therapy/methods , Animals , Breast Neoplasms/pathology , Cell Proliferation , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL
6.
PLoS One ; 11(4): e0154191, 2016.
Article in English | MEDLINE | ID: mdl-27123982

ABSTRACT

In recent years, comprehensive learning particle swarm optimization (CLPSO) has attracted the attention of many scholars for using in solving multimodal problems, as it is excellent in preserving the particles' diversity and thus preventing premature convergence. However, CLPSO exhibits low solution accuracy. Aiming to address this issue, we proposed a novel algorithm called LILPSO. First, this algorithm introduced a Lagrange interpolation method to perform a local search for the global best point (gbest). Second, to gain a better exemplar, one gbest, another two particle's historical best points (pbest) are chosen to perform Lagrange interpolation, then to gain a new exemplar, which replaces the CLPSO's comparison method. The numerical experiments conducted on various functions demonstrate the superiority of this algorithm, and the two methods are proven to be efficient for accelerating the convergence without leading the particle to premature convergence.


Subject(s)
Algorithms , Models, Statistical , Humans , Learning , Problem Solving
7.
Zhongguo Zhong Yao Za Zhi ; 40(10): 1908-13, 2015 May.
Article in Chinese | MEDLINE | ID: mdl-26390646

ABSTRACT

In order to reveal feasibility of different concentrations of Ca2+ and SA on Platycodon grandiflorum under high temperature stress, the effects of Ca2+ on physiological index and related photosynthetic parameters were studied. Pot cultured P. grandiflorum leaves under the same outdoor conditions were sprayed with CaCl2 and SA separately, and then placed in the high incubator [35 degrees C/25 degrees C (day/night), light intensity 3 600 lx], and sprayed with distilled water at 25 degrees C and under high temperature stress were set as the control. The related photosynthesis, relative conductivity, contents of proline, malondialdehyde, soluble protein, activities of SOD and CAT, ASA and GSH content were measured. The results show that the 6 mmol x L(-1) CaCl2 and 1.5 mmol x L(-1) SA enhanced the activities of SOD and CAT, the contents of proline and soluble protein, and effectively reduced the damage of heat stress on cell membrance. At the same time, the exogenous Ca2+ and SA increased the contents of chlorophyll and carotenoid, the efficiency of leaf photosynthesis and ASA and GSH content, and thus effectively resisted the oxidative stress caused by high temperatures, but with the increasing concentration of spraying, P. grandiflorum decreased the ability to resist high temperature stress. In conclusion, the foliage spraying CaCl2 and SA could reduce the damage of high temperature stress on P. grandiflorum leaves.


Subject(s)
Calcium/metabolism , Photosynthesis , Platycodon/metabolism , Salicylic Acid/metabolism , Hot Temperature , Malondialdehyde/metabolism , Oxidative Stress , Plant Leaves/metabolism , Stress, Physiological
8.
National Journal of Andrology ; (12): 925-930, 2015.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-275993

ABSTRACT

Spermatogenesis is a complex process. Current knowledge about human spermatogenesis is mainly based on the mouse model while little is known about the initial stage of this fundamental process in humans. The establishment of the model of spermatogenesis in vitro may contribute to an overall understanding of male germ cell development, an insight into the mechanisms of infertility, and clinical management of male infertility. This review summarizes current knowledge about the generation of germ cell-like cells from induced pluripotent stem cells (iPSCs) in vitro and discusses the potential application of iPSCs in the treatment of male infertility.


Subject(s)
Animals , Humans , Male , Mice , Cell Differentiation , Germ Cells , Induced Pluripotent Stem Cells , Infertility, Male , Therapeutics , Spermatogenesis
9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-351241

ABSTRACT

In order to reveal feasibility of different concentrations of Ca2+ and SA on Platycodon grandiflorum under high temperature stress, the effects of Ca2+ on physiological index and related photosynthetic parameters were studied. Pot cultured P. grandiflorum leaves under the same outdoor conditions were sprayed with CaCl2 and SA separately, and then placed in the high incubator [35 degrees C/25 degrees C (day/night), light intensity 3 600 lx], and sprayed with distilled water at 25 degrees C and under high temperature stress were set as the control. The related photosynthesis, relative conductivity, contents of proline, malondialdehyde, soluble protein, activities of SOD and CAT, ASA and GSH content were measured. The results show that the 6 mmol x L(-1) CaCl2 and 1.5 mmol x L(-1) SA enhanced the activities of SOD and CAT, the contents of proline and soluble protein, and effectively reduced the damage of heat stress on cell membrance. At the same time, the exogenous Ca2+ and SA increased the contents of chlorophyll and carotenoid, the efficiency of leaf photosynthesis and ASA and GSH content, and thus effectively resisted the oxidative stress caused by high temperatures, but with the increasing concentration of spraying, P. grandiflorum decreased the ability to resist high temperature stress. In conclusion, the foliage spraying CaCl2 and SA could reduce the damage of high temperature stress on P. grandiflorum leaves.


Subject(s)
Calcium , Metabolism , Hot Temperature , Malondialdehyde , Metabolism , Oxidative Stress , Photosynthesis , Plant Leaves , Metabolism , Platycodon , Metabolism , Salicylic Acid , Metabolism , Stress, Physiological
10.
Cancer Biol Med ; 11(1): 34-43, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24738037

ABSTRACT

In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles (MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanoparticles, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.

11.
Acta Pharmacol Sin ; 34(4): 531-40, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23503473

ABSTRACT

AIM: The tumor suppressor in lung cancer-1 (TSLC1) is a candidate tumor suppressor of lung cancer, and frequently inactivated in primary non-small cell lung cancer (NSCLC). In this study, we investigated the effects of TSLC1 mediated by a dual-regulated oncolytic adenovirus on lung cancer, and the mechanisms underlying the antitumor actions. METHODS: The recombinant virus Ad·sp-E1A(Δ24)-TSLC1 was constructed by inserting the TSLC1 gene into the dual-regulated Ad·sp-E1A(Δ24) vector, which contained the survivin promoter and a 24 bp deletion within E1A. The antitumor effects of Ad·sp-E1A(Δ24)-TSLC1 were evaluated in NCI-H460, A549, and H1299 lung cancer cell lines and the normal fibroblast cell line MRC-5, as well as in A549 xenograft model in nude mice. Cell viability was assessed using MTT assay. The expression of TSLC1 and activation of the caspase signaling pathway were detected by Western blot analyses. The tumor tissues from the xenograft models were examined using H&E staining, IHC, TUNEL, and TEM analyses. RESULTS: Infection of A549 lung cancer cells with Ad·sp-E1A(Δ24)-TSLC1 induced high level expression of TSLC1. Furthermore, the Ad·sp-E1A(Δ24)-TSLC1 virus dose-dependently suppressed the viability of NCI-H460, A549, and H1299 lung cancer cells, and did not affect MRC-5 normal fibroblast cells. Infection of NCI-H460, A549, and H1299 lung cancer cells with Ad·sp-E1A(Δ24)-TSLC1 induced apoptosis, and increased activation of caspase-8, caspase-3 and PARP. In A549 xenograft model in nude mice, intratumoral injection of Ad·sp-E1A(Δ24)-TSLC1 significantly suppressed the tumor volume, and increased the survival rate (from less than 15% to 87.5% at d 60). Histological studies showed that injection of Ad·sp-E1A(Δ24)-TSLC1 caused tumor cell apoptosis and virus particle propagation in tumor tissues. CONCLUSION: The oncolytic adenovirus Ad·sp-E1A(Δ24)-TSLC1 exhibits specific antitumor effects, and is a promising agent for the treatment of lung cancer.


Subject(s)
Adenoviridae/physiology , Cell Adhesion Molecules/genetics , Immunoglobulins/genetics , Lung Neoplasms/therapy , Oncolytic Viruses/physiology , Tumor Suppressor Proteins/genetics , Animals , Apoptosis/physiology , Cell Adhesion Molecule-1 , Cell Adhesion Molecules/metabolism , Cell Line , Cell Line, Tumor , Female , Fibroblasts/metabolism , Fibroblasts/virology , Genetic Therapy/methods , Genetic Vectors/genetics , Genetic Vectors/metabolism , HEK293 Cells , Humans , Immunoglobulins/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/virology , Mice , Mice, Inbred BALB C , Oncolytic Virotherapy/methods , Random Allocation , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Tumor Suppressor Proteins/metabolism
12.
Huan Jing Ke Xue ; 32(3): 742-8, 2011 Mar.
Article in Chinese | MEDLINE | ID: mdl-21634173

ABSTRACT

To investigate the mechanisms of tritium persistence in clay minerals, three types of clay soils (montmorillonite, kaolinite and illite) and tritiated water were used in this study to conduct the tritium sorption tests and the other related tests. Firstly, the ingredients, metal elements and heat properties of clay minerals were studied with some instrumental analysis methods, such as ICP and TG. Secondly, with a specially designed fractionation and condensation experiment, the adsorbed water, the interlayer water and the structural water in the clay minerals separated from the tritium sorption tests were fractionated for investigating the tritium distributions in the different types of adsorptive waters. Thirdly, the location and configuration of tritium adsorbed into the structure of clay minerals were studied with infrared spectrometry (IR) tests. And finally, the forces and mechanisms for driving tritium into the clay minerals were analyzed on the basis of the isotope effect of tritium and the above tests. Following conclusions have been reached: (1) The main reason for tritium persistence in clay minerals is the entrance of tritium into the adsorbed water, the interlayer water and the structural water in clay minerals. The percentage of tritium distributed in these three types of adsorptive water are in the range of 13.65% - 38.71%, 0.32% - 5.96%, 1.28% - 4.37% of the total tritium used in the corresponding test, respectively. The percentages are different for different types of clay minerals. (2) Tritium adsorbed onto clay minerals are existed in the forms of the tritiated hydroxyl radical (OT) and the tritiated water molecule (HTO). Tritium mainly exists in tritiated water molecule for adsorbed water and interlayer water, and in tritiated hydroxyl radical for structural water. (3) The forces and effects driving tritium into the clay minerals may include molecular dispersion, electric charge sorption, isotope exchange and tritium isotope effect.


Subject(s)
Aluminum Silicates/chemistry , Environmental Pollutants/analysis , Minerals/chemistry , Tritium/analysis , Adsorption , Bentonite/chemistry , Clay , Environmental Monitoring , Kaolin/chemistry , Porosity
13.
Chinese Journal of Cardiology ; (12): 301-304, 2011.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-272255

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.</p><p><b>METHODS</b>Twenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.</p><p><b>RESULTS</b>Compared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.</p><p><b>CONCLUSIONS</b>LPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.</p>


Subject(s)
Animals , Rabbits , Anti-Arrhythmia Agents , Pharmacology , Arrhythmias, Cardiac , Metabolism , Connexin 43 , Metabolism , Lysophospholipids , Oligopeptides , Pharmacology
14.
Chinese Journal of Cardiology ; (12): 1102-1107, 2010.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-244095

ABSTRACT

<p><b>OBJECTIVE</b>The aim of this study is to observe the effect of combined amiodarone and antiarrhythmic peptide (AAP10) use on the incidence of induced ventricular arrhythmias in healed myocardial infarction (MI) rabbits.</p><p><b>METHODS</b>Twenty Japanese rabbits underwent thoracotomy without coronary artery ligation (Sham, group A), the middle left circumflex branch were ligated to induce MI in 180 Japanese rabbits. Eight weeks after operation, 124 rabbits survived MI operation and were divided into four groups: control group (group B, n = 31), amiodarone group (group C, n = 31), AAP10 group (group D, n = 31) and amiodarone plus AAP10 group (group E, n = 31). The A and B and D groups were treated with saline 2 ml/d, the C and E groups were treated with 2 ml saline containing amiodarone 100 mg×kg(-1)×d(-1). All rabbits were examined by echocardiogram at 12 weeks after operation, then anesthetized by sodium barbital, the left wedge ventricular preparations were cannulated and artery perfused by Tyrode's solution in vitro in the absence (Group A, B and C) and presence of AAP10 (500 nmol/L, Group D and E). The volume electrocardiogram, QT Interval, QRS interval, effective refractory period (ERP), the T-peak to T-end interval (T(p-e)), and ventricular tachycardia episodes induced by programmed stimulation were recorded. The T(p-e)/QT ratio was calculated. After perfusion, gap junctions protein connexin 43 (Cx43) expression was detected by Western blot and immunofluorescence.</p><p><b>RESULTS</b>The incidence of induced ventricular tachycardia episodes of group A, B, C, D, E was 0, 62.5%, 26.9%, 40.0%, 22.2% respectively. The incidence of induced ventricular tachycardia episodes of group E was less than group B. The T(p-e)/QT ratio in group B, C, D were greater than in group A. The T(p-e)/QT ratio of group E was less than group B. The myocardial Cx43 in the group B was down-regulated and disorganized compared to group A, up-regulated in group C and E compared to group B, up-regulated in group E compared to group D. The Cx43 in the heart of group D and E were well organized than in group B and C.</p><p><b>CONCLUSIONS</b>The artery perfused rabbits wedge preparations with healed myocardial infarction with high incidence of induced ventricular tachycardia episodes are good platform for ventricular arrhythmias research. Combined amiodarone and AAP10 use could decrease the T(p-e)/QT ratio and the incidence of induced ventricular tachycardia episodes. Amiodarone and AAP10 have synergistic effects on upregulating Cx43 and preventing ventricular arrhythmias in this rabbit model of healed myocardial infarction.</p>


Subject(s)
Animals , Male , Rabbits , Amiodarone , Pharmacology , Therapeutic Uses , Anti-Arrhythmia Agents , Pharmacology , Therapeutic Uses , Arrhythmias, Cardiac , Connexin 43 , Metabolism , Myocardial Infarction , Drug Therapy , Metabolism , Oligopeptides , Pharmacology , Therapeutic Uses , Treatment Outcome
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