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1.
Mar Drugs ; 20(11)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36355009

RESUMO

It has been reported that the giant triton snail (Charonia tritonis) inserts its large proboscis and then injects venom or acid saliva from its salivary gland into its prey, the crown-of-thorns starfish Acanthaster planci (COTS), paralyzing it. A full-length cDNA sequence of the C. tritonis Ct-kunitzin gene was obtained by RACE PCR based on a transcriptomic database constructed by our laboratory (data not published), which contains an open reading frame (ORF) sequence with a length of 384 bp including a 1-32aa Kunitz domain. The Ct-kunitzin peptide was synthesized by solid-phase polypeptide methods according to its conserved amino acid sequence, with a molecular weight of 3746.0 as well as two disulfide bonds. Renatured Ct-kunitzin was injected into mice ventricles to evaluate its potential function. Compared with the normal control group (physiological saline), the spontaneous locomotor activity of the Ct-kunitzin group decreased significantly. There was a significant effect on Ct-kunitzin on mice grip strength in the grip strength test. In addition, Ct-kunitzin exhibited remarkable biological activity in suppressing pain in the pain thresholds test. There were no significant differences between the Ct-kunitzin group and the normal control group in terms of various hematological indexes and histopathological observations. When tested in COTS, the most significant histological change was the destruction, disorganization, and significant reduction in the amount of COTS tube feet tissues. Altogether, the potential paralyzing effect on mice suggests that Ct-kunitzin is a possible agent for novel drug development.


Assuntos
Caramujos , Estrelas-do-Mar , Camundongos , Animais , Estrelas-do-Mar/química , Sequência de Aminoácidos , Transcriptoma , Peptídeos/genética
2.
Int J Mol Sci ; 23(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36362196

RESUMO

Macrophage-expressed gene 1 proteins (Mpeg1/Perforin-2 (PRF2)) are a family of pore-forming proteins (PFPs) which can form pores and destroy the cell membrane of invading pathogens. However, little information is available regarding the function of Mpeg1 in the giant triton snail Charonia tritonis. In this study, a homolog of Mpeg1 (Ct-Mpeg1) was identified in C. tritonis. The predicted protein of Ct-Mpeg1 contains several structural features known in Mpegs, including a membrane attack complex/perforin (MACPF) domain and single transmembrane region. The Ct-Mpeg1 gene was constitutively expressed in almost all tissues examined except in the proboscis, with the highest expression level observed in the mantle. As a typical pore-forming protein, Ct-Mpeg1 has antibacterial activities against Vibrio (including Vibrio alginolyticus and Vibrio parahaemolyticus). In addition, rCt-Mpeg1 challenge to V. alginolyticus represses the expression of most outer membrane protein synthesis-related genes and genes involved in the TCA cycle pathway, which will lead to reduced outer membrane protein synthesis and less energy capacity. This is the first report to characterize the macrophage-expressed gene 1 protein in C. tritonis, and these results suggest that macrophage-expressed gene 1 protein Ct-Mpeg1 is an important immune molecule of C. tritonis that is involved in the bacterial infection resistance of Vibrio, and this study may provide crucial basic data for the understanding of the innate immunity system of C. tritonis.


Assuntos
Anti-Infecciosos , Proteínas de Membrana , Animais , Perforina/metabolismo , Proteínas de Membrana/metabolismo , Caramujos/genética , Imunidade Inata/genética , Macrófagos/metabolismo , Anti-Infecciosos/metabolismo
3.
Front Psychol ; 13: 1024286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312150

RESUMO

Short-form travel videos are popular, but the process of audience involvement while watching remains unclear. This study explores audience involvement along with expressions of travel intention and introduces the concepts of destination image and psychological distance to construct a structural model. A total of 487 questionnaires were used for structural equation model testing. Results show that audience involvement has a positive impact on the destination's cognitive and affective image, ultimately leading to travel intention. Meanwhile, the destination's cognitive and affective image play a partial mediating role between the influencing mechanisms. Moreover, psychological distance has a negative moderating effect between audience involvement and travel intention, and on audience involvement and cognitive image. However, it has no significant moderating effect on both audience involvement and affective image. The results provide a broader research perspective for the development of short-form travel videos and provide important implications for destination marketing.

4.
Int J Mol Sci ; 23(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36232364

RESUMO

Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors (PRRs) involved in host antibacterial responses, and their functions have been characterized in most invertebrate and vertebrate animals. However, little information is available regarding the potential function of PGRPs in the giant triton snail Charonia tritonis. In this study, a short-type PGRP gene (termed Ct-PGRP-S1) was identified in C. tritonis. Ct-PGRP-S1 was predicted to contain several structural features known in PGRPs, including a typical PGRP domain (Amidase_2) and Src homology-3 (SH3) domain. The Ct-PGRP-S1 gene was constitutively expressed in all tissues examined except in proboscis, with the highest expression level observed in the liver. As a typical PRR, Ct-PGRP-S1 has an ability to degrade peptidoglycan (PGN) and was proven to have non-Zn2+-dependent amidase activity and antibacterial activity against Vibrioalginolyticus and Staphylococcus aureus. It is the first report to reveal the peptidoglycan recognition protein in C. tritonis, and these results suggest that peptidoglycan recognition protein Ct-PGRP-S1 is an important effector of C. tritonis that modulates bacterial infection resistance of V. alginolyticus and S. aureus, and this study may provide crucial basic data for the understanding of an innate immunity system of C. tritonis.


Assuntos
Peptidoglicano , Infecções Estafilocócicas , Amidoidrolases/metabolismo , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Transporte , Clonagem Molecular , Imunidade Inata , Peptidoglicano/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Caramujos/genética , Staphylococcus aureus/metabolismo
5.
Ann Noninvasive Electrocardiol ; 27(4): e12951, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35403309

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a very common type of cardiac arrhythmia that threatens public health. Aging is an independent AF risk factor. However, the mechanism of age-related AF remains unclear. METHODS: A total of 36 Beagle dogs were selected and divided into three groups (12 in each group): two groups were 9-year-old aged dogs, and one group was 4-year-old adult dogs. Electrophysiological testing was employed to determine if modeling is successful. Patch-clamp technique was employed to measure the If current. The expression of protein and mRNA related to If current were also tested. Collagen deposition was observed with the use of Masson staining. RESULTS: Aging resulted in a higher collagen deposition percentage in the left atrium. The hyperpolarization-activated cyclic nucleotide-gated (HCN)2 and HCN4 expressions were increased in the atria and pulmonary veins but decreased in the sinus node of the aged group. Moreover, in the aged group, the left atrium mRNA expressions of Kcnd2 (Potassium voltage-gated channel subfamily D member 2), Kcnh2, Kcnq1, Kcnj2, Kcnj11, and CACNA1H were significantly downregulated. The aged AF group also demonstrated sustained AF and significant changes in electrophysiological characteristics. The If current demonstrated an increased amplitude and was easier to activate in the aged AF group than in younger group. Finally, AF occurrence exacerbated aging-induced cardiac fibrosis, thereby aggravating the above-listed symptoms. CONCLUSION: With age, the increase in atrial fibrosis affected the expression of the ion channels, thereby modulating the If current. Moreover, AF also further exacerbated the degree of atrial fibrosis.


Assuntos
Fibrilação Atrial , Envelhecimento/fisiologia , Animais , Colágeno/metabolismo , Colágeno/farmacologia , Cães , Eletrocardiografia , Fibrose , Átrios do Coração , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia
6.
Int J Mol Sci ; 23(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35163515

RESUMO

Antimony (Sb), a global and priority controlled pollutant, causes severe environmental issues. Bioremediation by microbial communities containing sulfate-reducing bacteria (SRB) is considered to be among the safest, economical, and environmentally friendly methods to remove Sb from wastewater. However, the roles of SRB species in these communities remain uncertain, and pure cultures of bacteria that may be highly efficient have not yet been developed for Sb removal. In this study, an Sb tolerant community was enriched from municipal sludge, and molecular ecological analysis showed that Escherichia (40%) and Desulfovibrio (15%) were the dominant bacteria. Further isolation and identification showed that the enriched SRB strains were closely related to Cupidesulfovibrio oxamicus, based on the molecular analyses of 16S rRNA and dsrB genes. Among them, a strain named SRB49 exhibited the highest activity in removal of Sb(V). SRB49 was able to remove 95% of Sb(V) at a concentration of 100 mg/L within 48 h under optimum conditions: a temperature of 37-40 °C, an initial pH value of 8, 4 mM of sulfate, and an initial redox potential of 145-229 mV. SEM-EDX analysis showed that SRB49 did not adsorb Sb(V) but reduced and precipitated Sb(V) via the formation of Sb2S3. The results demonstrated the potential roles that pure cultures of SRB species may play in Sb removal and the use of Sb-tolerant SRB strains for Sb remediation.


Assuntos
Antimônio/análise , Bactérias/classificação , Esgotos/microbiologia , /microbiologia , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Biodegradação Ambiental , Cidades , Sequenciamento de Nucleotídeos em Larga Escala , Oxirredução , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Sulfatos/química , /química
7.
Artigo em Inglês | MEDLINE | ID: mdl-35118574

RESUMO

PURPOSE: Previous studies demonstrated M2 muscarinic acetylcholine receptor-activating autoantibodies (M2R-AAb) were present in some patients with postural tachycardia syndrome (POTS). This study examines how these autoantibodies might contribute to the pathophysiology of POTS, and whether low-level tragus stimulation (LLTS) can ameliorate autoantibody-mediated autonomic dysregulation in the rabbit. METHODS: Five New Zealand white rabbits were immunized with a M2R second extracellular loop peptide to produce cholinomimetic M2R-AAb. Tilt test and infusion studies were performed on conscious rabbits before immunization, 6 weeks after immunization, and 8 weeks after immunization with 2-week daily LLTS treatment. Each rabbit served as its own control. RESULTS: Compared to preimmune state, an enhanced heart rate increase and decreased parasympathetic activity upon tilting were observed in immunized rabbits. Furthermore, these rabbits demonstrated an attenuated heart rate-slowing response to infusion of the M2R orthosteric agonist arecaidine propargyl ester (APE), suggesting an inhibitory allosteric effect of M2R-AAb. There was also a significant increase in serum inflammatory cytokines in immunized rabbits. LLTS treatment suppressed the postural tachycardia, improved the sympathovagal balance with increased acetylcholine secretion, reduced the levels of inflammatory cytokines, and reversed the attenuated heart rate response to APE in immunized rabbits. No suppression of M2R-AAb expression by LLTS was found during this short-term study period. Receptor-modulating activity of M2R-AAb produced in immunized rabbits was confirmed with in vitro bioassay. CONCLUSIONS: Autoantibody inhibition of cholinergic ligand activity may be involved in the development of cardiovagal dysfunction and inflammation associated with POTS, both of which can be improved by vagal stimulation.

8.
J Cardiovasc Transl Res ; 15(2): 438-440, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34409582

RESUMO

Functional autoantibodies directed to the M2 muscarinic acetylcholine receptor (M2R) could affect the heart rate directly by altering cardiac M2R activity and/or indirectly by changing vagal-mediated cardiac M2R activity. We measured M2R autoantibody activity in sera from 10 subjects with postural tachycardia syndrome (POTS) and 5 healthy control subjects using a cell-based bioassay. Half of the POTS subjects demonstrated presence of elevated M2R autoantibody activity, while no significant M2R autoantibody activity was found in the healthy subjects. Serum-derived immunoglobulin G (IgG) from antibody-positive POTS patients induced a dose-dependent activation of M2R, which was blocked by the muscarinic antagonist atropine. Moreover, antibody-positive POTS IgG decreased the responsiveness to oxotremorine, an orthosteric muscarinic agonist, indicating an indirect inhibitory effect. These data suggest that M2R autoantibodies may contribute to the pathophysiology of POTS by increasing the normal vagal withdrawal during upright posture through its negative allosteric modulation of M2R activity. M2 muscarinic receptor-activating autoantibodies are present in a subgroup of patients with POTS and act as a negative allosteric modulator of the orthosteric ligand response.


Assuntos
Antagonistas Muscarínicos , Síndrome da Taquicardia Postural Ortostática , Autoanticorpos , Frequência Cardíaca , Humanos , Antagonistas Muscarínicos/farmacologia , Síndrome da Taquicardia Postural Ortostática/diagnóstico , Receptor Muscarínico M2
9.
J Agric Food Chem ; 70(1): 229-237, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34955018

RESUMO

The study aims to enhance ß-amyrin production in Saccharomyces cerevisiae by peroxisome compartmentalization. First, overaccumulated squalene was determined as a key limiting factor for the production of ß-amyrin since it could inhibit the activity of ß-amyrin synthase GgbAs1. Second, to mitigate the inhibition effect, the enhanced squalene synthesis pathway was compartmentalized into peroxisomes to insulate overaccumulated squalene from GgbAs1, and thus the specific titer of ß-amyrin reached 57.8 mg/g dry cell weight (DCW), which was 2.6-fold higher than that of the cytosol engineering strain. Third, by combining peroxisome compartmentalization with the "push-pull-restrain" strategy (ERG1 and GgbAs1 overexpression and ERG7 weakening), the production of ß-amyrin was further increased to 81.0 mg/g DCW (347.0 mg/L). Finally, through fed-batch fermentation in a 5 L fermenter, the titer of ß-amyrin reached 2.6 g/L, which is the highest reported to date. The study provides a new perspective to engineering yeasts as a platform for triterpene production.


Assuntos
Engenharia Metabólica , Ácido Oleanólico/biossíntese , Saccharomyces cerevisiae , Esqualeno , Microbiologia Industrial , Transferases Intramoleculares , Ácido Oleanólico/análogos & derivados , Saccharomyces cerevisiae/genética
10.
Top Stroke Rehabil ; : 1-9, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34927574

RESUMO

BACKGROUND: Patients with stroke usually use smartphones to obtain online information to maintain their health. But their ability to identify, evaluate and apply this information is still unknown. AIM: This study was designed to examine the reliability and validity of the electronic Health Literacy Scale among patients with stroke in China. DESIGN: This is a cross-sectional survey. METHODS: A demographic questionnaire, the electronic Health Literacy Scale (e-HLS) and the eHealth Literacy Scale (eHEALS) were administered to a sample of 648 patients with ischemic stroke recruited from December 2020 to March 2021 in a tertiary hospital. RESULTS: The Cronbach'α coefficient on the e-HLS-CHI was 0.907. Kappa consistency coefficient of test-retest reliability was 0.691 (p < .05). Three factors were extracted by Exploratory Factor Analysis (EFA), accounting for 90.84% of the total variance. Confirmatory Factory Analysis (CFA) revealed that three factors of e-HLS-CHI fit well (NFI = 0.979, RFI = 0.955, IFI = 0.987, TLI = 0.972, CFI = 0.987, RMSEA = 0.070, CMIN/DF = 2.586). Good simultaneous validity was suggested by the positive correlation of 0.94 (p < .001) between the e-HLS-CHI and eHEALS. When using eHEALS as the standard, the area under the ROC curve of e-HLS-CHI was 0.896 (95% CI: 0.831-0.960, p < .001). The sensitivity and specificity were 97.8% and 70.4% respectively. CONCLUSIONS: The e-HLS can be used to evaluate electronic health literacy of patients with stroke in China after translation and cultural adaption.

11.
Neuropsychiatr Dis Treat ; 17: 3085-3095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675520

RESUMO

PURPOSE: To examine the effectiveness of goal-based health management on health knowledge, health belief and health behavior in people at high risk of stroke. PATIENTS AND METHODS: This is a two-armed and non-randomized controlled trial from May 31, 2020 to December 31, 2020. Participants were arranged to receive regular health care (n=126) or goal-based health management (n=126). The generalized estimation equation was used to analyze the changes in the participants' health knowledge, health belief and health behavior at baseline (T0), 1-month (T1), 3-month (T3), and 6-month (T6). RESULTS: A total of 243 participants completed the 6-month study, of which 123 were in the control group and 120 were in the intervention group. After receiving goal-based health management, participants' health behavior (ß=27.154, p<0.001), health knowledge (ß=10.504, p<0.001) and health belief (ß=49.057, p<0.001) scores increased significantly. CONCLUSION: Goal-based health management can effectively improve the health knowledge, health belief and health behavior of people at high risk of stroke. We recommend that nurses can provide goal-based health management for people at high risk of stroke with support from hospitals and family members of people at high risk of stroke.

12.
Front Physiol ; 12: 632518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732164

RESUMO

The giant triton snail (Charonia tritonis), an endangered gastropod species of ecological and economic importance, is widely distributed in coral reef ecosystems of the Indo-West Pacific region and the tropical waters of the South China Sea. Limited research on molecular mechanisms can be conducted because the complete genomic information on this species is unavailable. Hence, we performed transcriptome sequencing of the C. tritonis foot muscle and mantle using the Illumina HiSeq sequencing platform. In 109,722 unigenes, we detected 7,994 (3,196 up-regulated and 4,798 down-regulated) differentially expressed genes (DEGs) from the C. tritonis foot muscle and mantle transcriptomes. These DEGs will provide valuable resources to improve the understanding of molecular mechanisms involved in biomineralization of C. tritonis. In the Gene Ontology (GO) database, DEGs were clustered into three main categories (biological processes, molecular functions, and cellular components) and were involved in 50 functional subcategories. The top 20 GO terms in the molecular function category included sulfotransferase activity, transferring sulfur-containing groups, and calcium ion binding, which are terms considered to be related to biomineralization. In KEGG classifications, transcriptomic DEGs were mainly enriched in glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate, and sulfur metabolism pathway, which may be related to biomineralization. The results of qPCR showed that three of the eight genes examined were significantly up-regulated in the mantle. The phylogenetic tree of BMP1 suggested a significant divergence between homologous genes in C. tritonis. Our results improve the understanding of biomineralization in C. tritonis and provide fundamental transcriptome information to study other molecular mechanisms such as reproduction.

13.
Exp Physiol ; 106(4): 882-890, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33550676

RESUMO

NEW FINDINGS: What is the central question of this study? Do autoantibodies to the M2 muscarinic receptor (M2R-AAbs) have the potential to facilitate specific sustained tachyarrhythmias in the presence of thyroxine (T4 ) in rabbits? What is the main finding and its importance? The M2R-AAb and T4 jointly destabilized the electrophysiological properties, thus promoting the occurrence of atrial and sinus tachyarrhythmias in rabbits. These findings provide a practical basis for understanding the pathophysiological role of M2R-AAb alone and with T4 in arrhythmia induction and might provide an innovative option for treatment of Graves' disease with rhythm disturbance. ABSTRACT: Activating autoantibodies toward the ß1/2 -adrenergic receptors (ß1/2AR-AAbs) and M2 muscarinic receptor (M2R-AAbs) are present in a high proportion of patients with Graves' disease. We previously demonstrated that ß1/2AR-AAbs with or without the presence of M2R-AAbs in combination with excessive thyroxine (T4 ) increased the induction of sustained tachyarrhythmias in an autoimmune rabbit model. However, the separate role of M2R-AAbs and their interaction with T4 are not clear. The aim of this study was to investigate the impact of M2R-AAbs and T4 on the induction of cardiac arrhythmias in a similar rabbit model. Ten New Zealand White rabbits were randomly divided into two groups. In group A (n = 6), the rabbits were immunized with the second extracellular loop peptide of M2R and subjected to 2 weeks of T4 treatment. In group B (n = 4), the rabbits were treated only with T4 for 2 weeks. After induction of general anaesthesia, rabbits were subjected to an electrophysiological study at 0 (pre-immune), 6 (post-immune) and 8 weeks (post-immune+T4 treatment) in group A and at 0 (baseline) and 8 weeks (T4 treatment) in group B. Each rabbit served as its own control. In group A, high levels and activity of M2R-AAbs were detected in all immunized animals. Thyroxine in combination with immunization significantly increased induction of sustained sinus tachycardia and atrial fibrillation in comparison to the pre-immune state. In group B, T4 predominantly induced sustained sinus tachycardia. This study demonstrated that M2R-AAbs and T4 jointly increased the susceptibility to both sinus and atrial tachyarrhythmias. The data supported the pathophysiological role of M2R-AAbs in hyperthyroidism-associated supraventricular tachyarrhythmias.


Assuntos
Fibrilação Atrial , Animais , Autoanticorpos , Colinérgicos , Humanos , Coelhos , Receptores Adrenérgicos beta 1 , Taquicardia Sinusal , Hormônios Tireóideos
14.
Exp Physiol ; 106(4): 902-912, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33576068

RESUMO

NEW FINDINGS: What is the central question of this study? Is there a causal relationship between gonadotrophin-releasing hormone (GnRH) receptor-activating autoantibodies and polycystic ovary syndrome (PCOS)? What is the main finding and its importance? Induction of GnRH receptor-activating autoantibodies in rats resulted in increased luteinizing hormone pulsatility and testosterone concentrations, disrupted oestrous cycles, increased atretic follicles, and activation of insulin signalling in the pituitary and ovary. These changes replicate those seen in humans with PCOS, suggesting that GnRH receptor-activating autoantibodies might be involved in the pathogenesis of PCOS. ABSTRACT: Gonadotrophin-releasing hormone receptor-activating autoantibodies (GnRHR-AAb) are associated with polycystic ovary syndrome (PCOS). In the present study, we examined the impact of GnRHR-AAb on reproductive function in GnRHR-immunized female rats. All immunized rats produced high titres of GnRHR-AAb targeting a dominant epitope located in the central region of the second extracellular loop of the GnRHR. Increased pulsatile luteinizing hormone secretion and testosterone concentrations were found in immunized rats. These rats exhibited disrupted oestrous cycles, increased ovarian follicular atresia, and activation of insulin signalling in the pituitary and ovary, as indicated by increased mRNA expressions of insulin receptor substrate, phosphatidylinositol 3-kinase and glucose transporter 1. No significant changes in inflammatory cytokines were detected in the ovarian tissue. These features mimic those observed in humans with PCOS. Our findings support the concept that chronic stimulation of the GnRHR by GnRHR-AAb, with an associated increase in pituitary luteinizing hormone secretion and ovarian androgen overproduction, might represent a new aetiological mechanism for PCOS.


Assuntos
Síndrome do Ovário Policístico , Animais , Autoanticorpos , Feminino , Atresia Folicular , Hormônio Liberador de Gonadotropina , Hormônio Luteinizante , Síndrome do Ovário Policístico/metabolismo , Ratos , Receptores LHRH
15.
Artif Organs ; 45(4): 411-418, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33001439

RESUMO

This study aims to evaluate four pacemaker pocket cleaning methods for preventing implantation-related infections. This single-center trial prospectively randomized 910 patients undergoing first-time pacemaker implantation or replacement into four pocket cleaning methods: hemocoagulase (group A, n = 228), gentamicin (group B, n = 228), hemocoagulase plus gentamicin (group C, n = 227), and normal saline (group D, n = 227). Before implanting the pacemaker battery, the pockets were cleaned with gauze presoaked in the respective cleaning solutions. Then, these patients were followed up to monitor the occurrence of infections for 1 month after implantation. Twelve implantation-related infections occurred in 910 patients (1.32%): four patients from group A (1.75%), three patients from group B (1.32%), two patients from group C (0.88%), and three patients from group D (1.32%) (P > .05). Furthermore, two patients developed bloodstream infections (0.22%), and both of these patients were associated with pocket infection (one patient was from group A, while the other patient was from group C, respectively). No cases of infective endocarditis occurred. The differences in the number of infections in these study groups were not statistically significant. The application of hemocoagulase, gentamicin, hemocoagulase plus gentamicin, or normal saline on the presoaked gauze before implantation was equally effective in preventing pocket-associated infections.


Assuntos
Marca-Passo Artificial , Infecções Relacionadas à Prótese/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Idoso , Antibacterianos/farmacologia , Batroxobina/farmacologia , Feminino , Gentamicinas/farmacologia , Humanos , Masculino , Estudos Prospectivos , Solução Salina/farmacologia
16.
Physiol Rep ; 8(24): e14672, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356018

RESUMO

Polycystic ovary syndrome (PCOS), a metabolic and reproductive disease, is frequently associated with type 2 diabetes. We have demonstrated activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of the gonadotropin-releasing hormone receptor (GnRHR) are present in a significant subgroup of PCOS patients. It is unclear whether GnRHR-AAb can induce peripheral tissue insulin resistance (IR) in animal models. Sixteen rats were divided equally into a GnRHR ECL2 peptide-immunized group (IMM group) and a control group (CON group). Sera GnRHR-AAb titer, luteinizing hormone (LH), and testosterone (T) were higher in IMM rats compared with CON rats. No significant difference in fasting blood glucose was observed between the two groups. However, the plasma glucose level at other time points of the IMM group was higher than that of the CON group during an intraperitoneal glucose tolerance test (IPGTT) and an insulin tolerance test (ITT) (p < 0.01). These data support the likelihood of the GnRHR-AAb induction of glucose intolerance and IR. Compared with the CON group, the IMM group showed a significant increase in insulin-stimulated phosphorylation of IRS-1 (p-IRS-1 S636/639) and a decrease in insulin-stimulated phosphorylation of Akt (p-AKT S473). Expression of the glucose transport genes including GLUT-2 in liver and GLUT-4 in white adipose tissue and skeletal muscle was significantly decreased in IMM rats compared with the CON rats. Serum levels of proinflammatory cytokines (TNF-α, IL-1α, and IL-18) were increased, while anti-inflammatory cytokines (IL-4 and IL-10) were decreased in the IMM group. Taken together, elevated GnRHR-AAb enhanced LH, hyperandrogenism, and inflammation. These changes are likely related to the observed peripheral tissue IR through the downregulation of the insulin-stimulated IRS/PI3K/Akt/Glut signaling pathway.


Assuntos
Autoanticorpos/imunologia , Resistência à Insulina , Obesidade/metabolismo , Síndrome do Ovário Policístico/metabolismo , Receptores LHRH/imunologia , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Citocinas/sangue , Feminino , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley
17.
BMC Genomics ; 21(1): 481, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32660426

RESUMO

BACKGROUND: The pearl oyster Pinctada fucata martensii is an economically valuable shellfish for seawater pearl production, and production of pearls depends on its growth. To date, the molecular mechanisms of the growth of this species remain poorly understood. The transcriptome sequencing has been considered to understanding of the complexity of mechanisms of the growth of P. f. martensii. The recently released genome sequences of P. f. martensii, as well as emerging Pacific Bioscience (PacBio) single-molecular sequencing technologies, provide an opportunity to thoroughly investigate these molecular mechanisms. RESULTS: Herein, the full-length transcriptome was analysed by combining PacBio single-molecule long-read sequencing (PacBio sequencing) and Illumina sequencing. A total of 20.65 Gb of clean data were generated, including 574,561 circular consensus reads, among which 443,944 full-length non-chimeric (FLNC) sequences were identified. Through transcript clustering analysis of FLNC reads, 32,755 consensus isoforms were identified, including 32,095 high-quality consensus sequences. After removing redundant reads, 16,388 transcripts were obtained, and 641 fusion transcripts were derived by performing fusion transcript prediction of consensus sequences. Alternative splicing analysis of the 16,388 transcripts was performed after accounting for redundancy, and 9097 gene loci were detected, including 1607 new gene loci and 14,946 newly discovered transcripts. The original boundary of 11,235 genes on the chromosomes was corrected, 12,025 complete open reading frame sequences and 635 long non-coding RNAs (LncRNAs) were predicted, and functional annotation of 13,482 new transcripts was achieved. Two thousand three hundred eighteen alternative splicing events were detected. A total of 228 differentially expressed transcripts (DETs) were identified between the largest (L) and smallest (S) pearl oysters. Compared with the S, the L showed 99 and 129 significantly up-and down-regulated DETs, respectively. Six of these DETs were further confirmed by quantitative real-time RT-PCR (RT-qPCR) in independent experiment. CONCLUSIONS: Our results significantly improve existing gene models and genome annotations, optimise the genome structure, and in-depth understanding of the complexity and diversity of the differential growth patterns of P. f. martensii.


Assuntos
Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Pinctada/genética , RNA-Seq/métodos , Transcriptoma , Processamento Alternativo/genética , Animais , Biologia Computacional , Fases de Leitura Aberta/genética , Pinctada/crescimento & desenvolvimento , RNA Longo não Codificante/genética , RNA Longo não Codificante/isolamento & purificação
18.
J Am Heart Assoc ; 8(19): e013006, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31547749

RESUMO

Background Previous studies have demonstrated that functional autoantibodies to adrenergic receptors may be involved in the pathogenesis of postural tachycardia syndrome. The objective of this study was to examine the impact of these autoantibodies on cardiovascular responses to postural changes and adrenergic orthosteric ligand infusions in immunized rabbits. Methods and Results Eight New Zealand white rabbits were coimmunized with peptides from the α1-adrenergic receptor and ß1-adrenergic receptor (ß1AR). Tilt test and separate adrenergic agonist infusion studies were performed on conscious animals before and after immunization and subsequent treatment with epitope-mimetic peptide inhibitors. At 6 weeks after immunization, there was a greater percent increase in heart rate upon tilting compared with preimmune baseline. No significant difference in blood pressure response to tilting was observed. The heart rate response to infusion of the ß-adrenoceptor agonist isoproterenol was significantly enhanced in immunized animals, suggesting a positive allosteric effect of ß1AR antibodies. In contrast, the blood pressure response to infusion of the α1-adrenergic receptor agonist phenylephrine was attenuated in immunized animals, indicating a negative allosteric effect of α1-adrenergic receptor antibodies. Injections of antibody-neutralizing peptides suppressed the postural tachycardia and reversed the altered heart rate and blood pressure responses to orthosteric ligand infusions in immunized animals at 6 and 30 weeks. Antibody production and suppression were confirmed with in vitro bioassays. Conclusions The differential allosteric effect of α1-adrenergic receptor and ß1AR autoantibodies would lead to a hyperadrenergic state and overstimulation of cardiac ß1AR. These data support evidence for an autoimmune basis for postural tachycardia syndrome.


Assuntos
Autoanticorpos/sangue , Frequência Cardíaca , Fragmentos de Peptídeos/imunologia , Síndrome da Taquicardia Postural Ortostática/imunologia , Postura , Receptores Adrenérgicos beta 1/imunologia , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Imunização , Masculino , Fragmentos de Peptídeos/administração & dosagem , Síndrome da Taquicardia Postural Ortostática/sangue , Síndrome da Taquicardia Postural Ortostática/fisiopatologia , Coelhos , Receptores Adrenérgicos beta 1/administração & dosagem
19.
Cardiology ; 142(4): 244-249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31203274

RESUMO

BACKGROUND: Atrial fibrillation (AF), for which age is an independent risk factor, is the most common persistent arrhythmia. Monocyte chemoattractant protein-1-induced protein (MCPIP), a transcription factor that induces a series of inflammation and cell death procedures, has been indicated to cause cardiomyocyte death in ischemic cardiomyopathy. The objective of this research was to investigate the relationship between age-related AF and MCPIP. METHODS: A total of 1,084 participants were included in this study, including 542 AF patients and 542 non-AF controls. Their medical histories were collected and analyzed. Moreover, blood samples were collected, and ELISA tests for expression of the inflammatory factor MCPIP and the fibrosis biomarkers pro-collagen type III N-terminal peptide (PIIINP) and type I collagen C-terminal telopeptide (ICTP) were conducted. Finally, a correlation analysis of these inflammatory factors and biomarkers was performed based on the ELISA results. RESULTS: We compared the echocardiography results of AF patients and found that the left ventricular ejection fraction and left atrial appendage velocity decreased with age (p < 0.05). Moreover, ELISA analysis of these samples showed that the expression of MCPIP was the highest in elderly patients with AF (p < 0.05), and there was no significant difference in expression between adult AF patients and elderly controls (p > 0.05). Finally, the correlation analysis demonstrated that the expressions of MCPIP, PIIINP, and ICTP were positively correlated in the elderly AF patient group, the adult AF group, and the elderly control group (p < 0.05). CONCLUSION: MCPIP expression was higher in age-related AF than in the other patient groups and it was associated with AF-induced fibrosis.


Assuntos
Fibrilação Atrial/sangue , Quimiocina CCL2/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , China , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrose/sangue , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Am Heart Assoc ; 7(20): e009938, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30371294

RESUMO

Background Ventricular arrhythmia after myocardial infarction is the most important risk factor for sudden cardiac death, which poses a serious threat to human health. As the correlation between autonomic nervous systemic dysfunction and heart rhythm abnormality has been gradually revealed, remedies targeting autonomic nervous system dysfunction, especially the sympathetic nerve, have emerged. Among them, renal denervation is noted for its powerful effect on the inhibition of sympathetic nerve activity. We aim to investigate whether renal denervation can reduce ventricular arrhythmia after myocardial infarction and thus decrease the risk of sudden cardiac death. In addition, we explore the potential mechanism with respect to nerve activity and remodeling. Methods and Results Twenty-four beagles were randomized into the control (n=4), renal denervation (n=10), and sham (n=10) groups. Permanent left anterior descending artery ligation was performed to establish myocardial infarction in the latter 2 groups. Animals in the renal denervation group underwent both surgical and chemical renal denervation. Compared with dogs in the sham group, dogs in the renal denervation group demonstrated attenuated effective refractory period shortening and inhomogeneity, flattened restitution curve, increased ventricular threshold, and decreased ventricular arrhythmia. Heart rate variability assessment, catecholamine measurement, and nerve discharge recordings all indicated that renal denervation could reduce whole-body and local tissue sympathetic tone. Tissue analysis revealed a significant decrease in neural remodeling in both the heart and stellate ganglion. Conclusions Surgical and chemical renal denervation decreased whole-body and local tissue sympathetic activity and reversed neural remodeling in the heart and stellate ganglion. Consequently, renal denervation led to beneficial remodeling of the electrophysiological characteristics in the infarction border zone, translating to a decrease in ventricular arrhythmia after myocardial infarction.


Assuntos
Arritmias Cardíacas/prevenção & controle , Infarto do Miocárdio/fisiopatologia , Simpatectomia/métodos , Sistema Nervoso Simpático/fisiologia , Animais , Vasos Coronários/cirurgia , Cães , Ligadura , Plasticidade Neuronal/fisiologia , Distribuição Aleatória
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