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1.
Psychiatry Investig ; 21(6): 672-679, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38960445

RESUMO

OBJECTIVE: Borderline personality disorder (BPD) is known to share characteristics with a variety of personality disorders (PDs) and exhibits diverse patterns of defense mechanisms. To enhance our understanding of BPD, it's crucial to shift our focus from traditional categorical diagnostics to the dimensional traits shared with other PDs, as the borderline personality organization (BPO) model suggests. This approach illuminates the nuanced spectrum of BPD characteristics, offering deeper insights into its complexity. While studies have investigated the comorbidity of BPD with other PDs, research exploring the relationship between various personality factors and defense mechanisms within BPD itself has been scarce. The present study was undertaken to investigate the complex interrelationships between various personality factors and defense styles in individuals diagnosed with BPD. METHODS: Using a network analysis approach, data from 227 patients diagnosed with BPD were examined using the Defense Style Questionnaire and Personality Disorder Questionnaire-4+ for assessment. RESULTS: Intricate connections were observed between personality factors and defense styles. Significant associations were identified between various personality factors and defense styles, with immature defense styles, such as maladaptive and image-distorting being particularly prominent in BPD in the centrality analysis. The maladaptive defense style had the highest expected influence centrality. Furthermore, the schizotypal, dependent, and narcissistic personality factors demonstrated relatively high centrality within the network. CONCLUSION: Network analysis can effectively delineate the complexity of various PDs and defense styles. These findings are expected to facilitate a deeper understanding of why BPD exhibits various levels of organization and presents with heterogeneous characteristics, consistent with the perspectives proposed by the BPO.

2.
Front Mol Neurosci ; 17: 1421932, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38932934

RESUMO

Rho guanine nucleotide exchange factors (Rho GEFs) activate Rho GTPases, which act as molecular switches regulating various essential cellular functions. This study investigated the role of ARHGEF5, a Rho GEF known for its involvement in cell migration and invasion processes, in the context of brain development. We found that ARHGEF5 is essential for dendrite development during the early stages of neuronal growth. We also discovered that ARHGEF5 binds to Drebrin E, which is vital for coordinating actin and microtubule dynamics, and facilitates the interaction between Drebrin E and Cyclin-dependent kinase 5, which phosphorylates Drebrin E. Notably, ARHGEF5 deficiency resulted in a decrease in acetylated α-tubulin levels, and the expression of an α-tubulin acetylation mimetic mutant (K40Q) rescued the defects in dendrite development and neuronal migration, suggesting ARHGEF5's role in modulating microtubule stability. Additionally, ARHGEF5 was shown to influence Golgi positioning in the leading processes of migrating cortical neurons during brain development. Our study suggests that ARHGEF5 plays a crucial role in integrating cytoskeletal dynamics with neuronal morphogenesis and migration processes during brain development.

3.
Int J Mol Sci ; 25(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38892219

RESUMO

Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC50 value of 0.45 µM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 µM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.


Assuntos
Anoctamina-1 , Antineoplásicos , Hemina , Proteínas de Neoplasias , Neoplasias da Próstata , Humanos , Masculino , Anoctamina-1/metabolismo , Anoctamina-1/antagonistas & inibidores , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hemina/farmacologia , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/antagonistas & inibidores , Células PC-3 , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
4.
Nurs Outlook ; 72(5): 102222, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38908293

RESUMO

BACKGROUND: Health policy critically influences a national healthcare system and nurse's roles, working conditions, and professional development opportunities, especially in low- and middle-income countries. PURPOSE: To explore and prioritize the major challenges and solution, and establish policy directions for improving nursing education in the Kyrgyz Republic. METHODS: The key stakeholders of nursing practice, education, policymaking, and regulation were involved in this modified Delphi study. Following two rounds of exploring priority issues and potential strategies, the participants of the final round assembled for consensual discussions on the establishment of policy directions. DISCUSSION: Innovations in nursing education systems, building educational capacity, and ensuring educational outcomes were suggested and agreed upon for the sequential improvement of nursing education. Timely enactment of these policies will enable the Kyrgyz Republic to mitigate nursing shortages, improve the quality of healthcare services, and enhance overall public health outcomes. CONCLUSION: The policy suggestions derived from this study, including the improvement of nursing education quality and the assurance of nurses' competencies, have great potential for improving quality healthcare practice and sustaining an effective healthcare system.

5.
BMC Med Educ ; 24(1): 511, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720333

RESUMO

BACKGROUND: Nursing faculties need to develop digital competencies to effectively use information, communication, and technology-based nursing education. PURPOSE: The study aimed to develop and apply a theory-guided faculty development program on digital teaching competencies. METHODS: A faculty development program was developed. Between March and April 2020, three five-hour web workshops participated by ninety-three faculty members were held. The program was assessed via mixed methods, combining satisfaction surveys post-workshop with content analysis of open-ended questionnaires to gauge participant evaluation of program content and learning experience. RESULTS: Participants were highly satisfied with the program contents and their opportunity for integrating digital technology into education and improving faculty proficiency in digital teaching technology. CONCLUSIONS: The program provides faculties with the self-confidence and essential skills to teach students using information, communication, and technology-based nursing education by enhancing their digital teaching competencies. It is critical to integrate both digital proficiency and nursing practice education.


Assuntos
Docentes de Enfermagem , Desenvolvimento de Pessoal , Humanos , Competência Profissional , Feminino , Masculino , Educação em Enfermagem/métodos , Ensino , Inquéritos e Questionários , Desenvolvimento de Programas , Adulto
6.
Biomed Hub ; 9(1): 62-66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638677

RESUMO

Introduction: Minimal change disease (MCD) is most often primary but may occur secondary to other systemic diseases such as malignancy. In secondary MCD, spontaneous remission of nephrotic syndrome after the treatment of related diseases without steroid therapy is rare. Case Presentation: A 78-year-old man visited the outpatient clinic with foamy urine and generalized edema that had persisted for 2 months. The patient had nephrotic syndrome. Before a kidney biopsy, he underwent several tests to determine the secondary cause of the nephrotic syndrome. The serum CEA was slightly elevated, and colon cancer was detected in the sigmoid colon. MCD was diagnosed from a kidney biopsy. He immediately underwent surgery for colon cancer. Complete remission of the MCD was achieved within 2 weeks after surgery. Conclusion: Here, we report a rare case of a patient with secondary MCD who successfully achieved spontaneous remission after colon cancer surgery.

7.
Nurse Educ Today ; 139: 106222, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38663053

RESUMO

BACKGROUND: The metaverse, a rapidly evolving virtual environment, offers new opportunities for healthcare education. The effectiveness of the metaverse as a learning tool depends on user readiness and platform characteristics. AIM: This study aimed to examine the current use of metaverse platforms among nurses and nursing students in South Korea and explore the relationship between user characteristics and their metaverse experience, focusing on presence, usability, and user experience. DESIGN: This was a cross-sectional descriptive study. SETTINGS: Registered nurses and nursing students from various healthcare settings and educational institutions in South Korea participated in this study. PARTICIPANTS: This study included 428 participants, comprising 188 nurses and 240 nursing students. METHODS: Between September and November 2022, participants provided voluntary informed consent. The participants engaged with one of the following two metaverse platforms: ZEPETO (mobile-based) or Gather (screen-based). After four structured exploration phases, the participants completed online questionnaires. These surveys assessed general characteristics, metaverse self-efficacy, sense of presence, usability, and user experience. RESULTS: Most participants had previous experience with the metaverse and rated their metaverse self-efficacy at 3.60. Nurses scored higher than nursing students in terms of presence, usability, and user experience in the metaverse. Higher work self-efficacy in nurses and academic self-efficacy in nursing students were associated with more positive experiences in the metaverse. Nurses consistently rated higher across all subdomains of presence, usability, and user experience than nursing students. The type of metaverse platform also significantly influenced user experience. CONCLUSIONS: A significant proportion of Korean nurses and nursing students are familiar with the metaverse, reflecting a global trend towards virtual environments in education and healthcare. Although the metaverse holds promise for healthcare education, its effectiveness depends on user readiness, platform characteristics, and the development of a reliable, structured, and user-friendly educational programme.


Assuntos
Estudantes de Enfermagem , Humanos , Estudos Transversais , Estudantes de Enfermagem/psicologia , Estudantes de Enfermagem/estatística & dados numéricos , República da Coreia , Feminino , Inquéritos e Questionários , Masculino , Adulto , Enfermeiras e Enfermeiros/psicologia , Enfermeiras e Enfermeiros/estatística & dados numéricos , Autoeficácia , Interface Usuário-Computador
8.
Int J Mol Sci ; 25(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542293

RESUMO

Lactobacillus curvatus HY7602 fermented antler (FA) ameliorates sarcopenia and improves exercise performance by increasing muscle mass, muscle fiber regeneration, and mitochondrial biogenesis; however, its anti-fatigue and antioxidant effects have not been studied. Therefore, this study aimed to investigate the anti-fatigue and antioxidant effects and mechanisms of FA. C2C12 and HepG2 cells were stimulated with 1 mM of hydrogen peroxide (H2O2) to induce oxidative stress, followed by treatment with FA. Additionally, 44-week-old C57BL/6J mice were orally administered FA for 4 weeks. FA treatment (5-100 µg/mL) significantly attenuated H2O2-induced cytotoxicity and reactive oxygen species (ROS) production in both cell lines in a dose-dependent manner. In vivo experiments showed that FA treatment significantly increased the mobility time of mice in the forced swimming test and significantly downregulated the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), and lactate. Notably, FA treatment significantly upregulated the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione/oxidized glutathione ratio (GSH/GSSG) and increased the mRNA expression of antioxidant genes (SOD1, SOD2, CAT, GPx1, GPx2, and GSR) in the liver. Conclusively, FA is a potentially useful functional food ingredient for improving fatigue through its antioxidant effects.


Assuntos
Chifres de Veado , Cervos , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Chifres de Veado/metabolismo , Peróxido de Hidrogênio/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Fadiga/tratamento farmacológico , Fadiga/metabolismo
10.
Int J Mol Sci ; 25(1)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38203747

RESUMO

Inflammatory bowel disease (IBD), a chronic condition that causes persistent inflammation in the digestive system, is closely associated with the intestinal microbiome. Here, we evaluated the effects of Lactiplantibacillus plantarum HY7718 (HY7718) on IBD symptoms in mice with dextran sulfate sodium (DSS)-induced colitis. Oral administration of HY7718 led to significant improvement in the disease activity index score and the histological index, as well as preventing weight loss, in model mice. HY7718 upregulated the expression of intestinal tight junction (TJ)-related genes and downregulated the expression of genes encoding pro-inflammatory cytokines and genes involved in the TLR/MyD88/NF-κB signaling pathway. Additionally, HY7718 reduced the blood levels of pro-inflammatory cytokines, as well as reversing DSS-induced changes to the composition of the intestinal microbiome. HY7718 also increased the percentage of beneficial bacteria (Lactiplantibacillus and Bifidobacterium), which correlated positively with the expression of intestinal TJ-related genes. Finally, HY7718 decreased the population of pathogens such as Escherichia, which correlated with IBD symptoms. The data suggest that HY7718 improves intestinal integrity in colitis model mice by regulating the expression of TJ proteins and inflammatory cytokines, as well as the composition of the intestinal microflora. Thus, L. plantarum HY7718 may be suitable as a functional supplement that improves IBD symptoms and gut health.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Lactobacillus plantarum , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Inflamação/tratamento farmacológico , Citocinas , Modelos Animais de Doenças
11.
Medicine (Baltimore) ; 103(3): e36990, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38241588

RESUMO

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis, and recurrent IgAN is common after kidney transplantation (KT). Owing to the differences in various biopsy protocols and follow-ups in each study, the recurrence rate varies from 9.7% to 46%. Although the relapse rates are high, there is no definitive treatment for IgAN recurrence. METHODS: We present a case of successful management of proteinuria in recurrent IgAN after deceased donor KT. A 60-year-old man diagnosed with IgAN 20 years prior, who progressed to end-stage renal disease, underwent deceased donor KT 5 years prior and was admitted to our hospital with progressively increasing proteinuria. RESULTS: The pathological examination of the kidney biopsy specimen revealed recurrent IgAN. High-dose steroid treatment was initiated, and the patient was discharged while maintaining steroid treatment. However, outpatient follow-up showed that proteinuria did not decrease while steroids were maintained. Therefore, an angiotensin receptor blocker was administered after explaining its benefits to the patient. After the addition of angiotensin receptor blocker, proteinuria continued to decrease. CONCLUSION: This case report highlights the importance of using renin-angiotensin system inhibitors with supportive care in cases of suspected of recurrent IgAN after KT. It also emphasizes the need to prescribe renin-angiotensin system inhibitors when steroid therapy is unsuccessful in cases of recurrent IgAN after KT.


Assuntos
Glomerulonefrite por IGA , Transplante de Rim , Proteinúria , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Angiotensina/uso terapêutico , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/cirurgia , Rim/patologia , Transplante de Rim/efeitos adversos , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Recidiva , Esteroides
12.
Nanomicro Lett ; 16(1): 33, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38015283

RESUMO

Supported nanoparticles have attracted considerable attention as a promising catalyst for achieving unique properties in numerous applications, including fuel cells, chemical conversion, and batteries. Nanocatalysts demonstrate high activity by expanding the number of active sites, but they also intensify deactivation issues, such as agglomeration and poisoning, simultaneously. Exsolution for bottom-up synthesis of supported nanoparticles has emerged as a breakthrough technique to overcome limitations associated with conventional nanomaterials. Nanoparticles are uniformly exsolved from perovskite oxide supports and socketed into the oxide support by a one-step reduction process. Their uniformity and stability, resulting from the socketed structure, play a crucial role in the development of novel nanocatalysts. Recently, tremendous research efforts have been dedicated to further controlling exsolution particles. To effectively address exsolution at a more precise level, understanding the underlying mechanism is essential. This review presents a comprehensive overview of the exsolution mechanism, with a focus on its driving force, processes, properties, and synergetic strategies, as well as new pathways for optimizing nanocatalysts in diverse applications.

13.
Microorganisms ; 11(9)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37764098

RESUMO

The aim of this study was to identify new potential probiotics with improved storage stability and to evaluate their efficacy and safety. Sixty lactic acid bacteria strains were isolated from Korean traditional fermented foods, and their survival was tested under extreme conditions. Lactobacillus plantarum HY7718 (HY7718) showed the greatest stability during storage. HY7718 also showed a stable growth curve under industrial conditions. Whole genome sequencing revealed that the HY7718 genome comprises 3.26 Mbp, with 44.5% G + C content, and 3056 annotated Protein-coding DNA sequences (CDSs). HY7718 adhered to intestinal epithelial cells and was tolerant to gastric fluids. Additionally, HY7718 exhibited no hemolytic activity and was not resistant to antibiotics, confirming that it has probiotic properties and is safe for consumption. Additionally, we evaluated its effects on intestinal health using TNF-induced Caco-2 cells. HY7718 restored the expression of tight junction proteins such as zonular occludens (ZO-1, ZO-2), occludin (OCLN), and claudins (CLDN1, CLDN4), and regulated the expression of myosin light-chain kinase (MLCK), Elk-1, and nuclear factor kappa B subunit 1 (NFKB1). Moreover, HY7718 reduced the secretion of proinflammatory cytokines such as interleukin-6 (IL-6) and IL-8, as well as reducing the levels of peroxide-induced reactive oxygen species. In conclusion, HY7718 has probiotic properties, is safe, is stable under extreme storage conditions, and exerts positive effects on intestinal cells. These results suggest that L. plantarum HY7718 is a potential probiotic for use as a functional supplement in the food industry.

14.
Food Sci Biotechnol ; 32(10): 1435-1444, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37457410

RESUMO

Deer velvet (DV) is an oriental traditional medicine used to treat various diseases. The present study examined the effect of flavourzyme-derived DV extract (YC-1101) on macrophages and an immunosuppressed mouse model. YC-1101 induced activation of macrophages as measured by nitric oxide production, cell proliferation, and cytokine release via concentration-dependent phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and AKT, and nuclear translocation of p65 in macrophages. In addition, oral YC-1101 administration significantly increased splenocyte proliferation and natural killer cell activity in the immunosuppressed mouse model. Moreover, the levels of immune-related cytokines such as tumor necrotic factor-α, interferon-γ, and interleukin-2 were significantly increased by YC-1101 treatment comparable to the control group. Thus, these results suggest that YC-1101 is an efficient natural ingredient that has an immune-enhancing effect, and it might be a potential functional food for improving immunity.

15.
Front Psychiatry ; 14: 1293347, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38268560

RESUMO

Introduction: Borderline personality disorder (BPD) is characterized by interpersonal and emotional instabilities, recurring suicidal tendencies, and feelings of emptiness. Childhood adverse event is reported in 70%-80% of cases involving BPD. Furthermore, the deficiency in mentalization capacity plays a significant role in emotion dysregulation and social interaction problems within individuals with BPD. This study explored the relationship among childhood adverse experiences, mentalization capacity, and neurophysiological activity in patients with BPD. Methods: Resting-state electroencephalography was used to identify the neural correlates associated with childhood adversity and mentalization deficits. The participants included 45 patients with BPD and 15 healthy controls. Results: The BPD group exhibited reduced alpha activity during eyes-closed rest, indicating heightened arousal even during relaxation. Correlations were found between the power spectral density (PSD) and mentalization capacity in the delta and theta ranges, suggesting an association between PSD and emotional awareness and expression. Gamma activity negatively correlated with psychic equivalence, implying a blurring of the boundaries between internal mental experiences and the external world. Conclusion: These findings offer insights into the pathophysiology of BPD, provide potential diagnostic markers, and suggest personalized treatment approaches based on mentalization traits.

16.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36430803

RESUMO

Chloroquine (CQ) is an antimalaria drug that has been widely used for decades. However, CQ-induced pruritus remains one of the major obstacles in CQ treatment for uncomplicated malaria. Recent studies have revealed that MrgprX1 plays an essential role in CQ-induced itch. To date, a few MrgprX1 antagonists have been discovered, but they are clinically unavailable or lack selectivity. Here, a cell-based high-throughput screening was performed to identify novel antagonists of MrgprX1, and the screening of 2543 compounds revealed two novel MrgprX1 inhibitors, berbamine and closantel. Notably, berbamine potently inhibited CQ-mediated MrgprX1 activation (IC50 = 1.6 µM) but did not alter the activity of other pruritogenic GPCRs. In addition, berbamine suppressed the CQ-mediated phosphorylation of ERK1/2. Interestingly, CQ-induced pruritus was significantly reduced by berbamine in a dose-dependent manner, but berbamine had no effect on histamine-induced, protease-activated receptors 2-activating peptide-induced, and deoxycholic acid-induced itch in mice. These results suggest that berbamine is a novel, potent, and selective antagonist of MrgprX1 and may be a potential drug candidate for the development of therapeutic agents to treat CQ-induced pruritus.


Assuntos
Benzilisoquinolinas , Cloroquina , Camundongos , Animais , Cloroquina/efeitos adversos , Prurido/induzido quimicamente , Prurido/tratamento farmacológico , Histamina , Ubiquitina-Proteína Ligases
17.
World J Clin Cases ; 10(32): 11967-11973, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36405277

RESUMO

BACKGROUND: The trigeminocardiac reflex (TCR) is usually caused by an increased parasympathetic tone when pressure or traction is applied to the surrounding tissue of the trigeminal nerve. However, the inexperienced anesthesiologists may have challenges on the management of TCR patients. CASE SUMMARY: This is the case of an 18-year-old woman diagnosed with hemangioma of the upper lip. During the operation, about 1 h after surgery started, a constant 1:1 premature ventricular complex was detected, and blood pressure was decreased when approaching the deeper part with more strong traction for exposure of the part. Although the management of arrhythmias, such as lidocaine and atropine, was injected, arrhythmia induced by surgical stimulation could not be eliminated completely. As the traction repeated, bradycardia was also repeated, despite injecting additional atropine. Therefore, the anesthesiologist and the surgeon decided to perform the operation only to the extent that the vascular tissue was selectively removed only at the site without the reflex. CONCLUSION: With TCR, anesthesiologists should perform appropriate monitoring. In addition to proper drug administration, surgeons should be consulted to cope with stopping the surgery and setting the scope of the surgery even if the site is superficial.

18.
Int J Mol Sci ; 23(18)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36142527

RESUMO

Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor (GPCR) activated by proteolytic cleavage of its N-terminal domain. Once activated, PAR2 is rapidly desensitized and internalized by phosphorylation and ß-arrestin recruitment. Due to its irreversible activation mechanism, some agonists that rapidly desensitized PAR2 have been misconceived as antagonists, and this has impeded a better understanding of the pathophysiological role of PAR2. In the present study, we found that GB83, initially identified as a PAR2 antagonist, is a bona fide agonist of PAR2 that induces unique cellular signaling, distinct from trypsin and PAR2-activating peptide (AP). Activation of PAR2 by GB83 markedly elicited an increase in intracellular calcium levels and phosphorylation of MAPKs, but in a delayed and sustained manner compared to the rapid and transient signals induced by trypsin and PAR2-AP. Interestingly, unlike PAR2-AP, GB83 and trypsin induced sustained receptor endocytosis and PAR2 colocalization with ß-arrestin. Moreover, the recovery of the localization and function of PAR2 was significantly delayed after stimulation by GB83, which may be the reason why GB83 is recognized as an antagonist of PAR2. Our results revealed that GB83 is a bona fide agonist of PAR2 that uniquely modulates PAR2-mediated cellular signaling and is a useful pharmacological tool for studying the pathophysiological role of PAR2.


Assuntos
Cálcio , Receptor PAR-2 , Cálcio/metabolismo , Peptídeos , Receptor PAR-2/metabolismo , Tripsina , beta-Arrestinas
19.
Artigo em Inglês | MEDLINE | ID: mdl-35805554

RESUMO

In South Korea, the suicide rate is more than double the OECD average, and precise identification of the cause is required for suicide prevention. Psychological autopsy is used to reveal factors related to suicidal behavior; however, such studies are lacking in Korea. This study investigated the factors related to suicide using psychological autopsies in Incheon, a major city in Korea. In total, 46 cases were investigated using the Korea-Psychological Autopsy Checklist (K-PAC), and data on mental health conditions and psychosocial factors of suicide decedents and their families were analyzed. It was estimated that 87% of individuals of suicides had a mental health condition before death, but only 15.2% continued treatment or counseling. Most individuals who died of suicide showed warning signs before death, but only 19.6% of survivors of suicide loss noticed them. Mental health concerns before and after the death of the individual were also identified in more than half of their families. To prevent suicide, intensive and continuous treatment for psychiatric conditions and prompt recognition of active response to suicide warning signs are required. Care for the mental health of family members is also important.


Assuntos
Suicídio , Autopsia , Humanos , República da Coreia/epidemiologia , Fatores de Risco , Ideação Suicida , Suicídio/psicologia , Sobreviventes
20.
Int J Mol Sci ; 23(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35054966

RESUMO

Thrombin stimulates platelets via a dual receptor system of protease-activated receptors (PARs): PAR1 and PAR4. PAR1 activation induces a rapid and transient signal associated with the initiation of platelet aggregation, whereas PAR4 activation results in a prolonged signal, required for later phases, that regulates the stable formation of thrombus. In this study, we observed differential signaling pathways for thrombin-induced PAR1 and PAR4 activation in a human megakaryoblastic leukemia cell line, MEG-01. Interestingly, thrombin induced both calcium signaling and morphological changes in MEG-01 cells via the activation of PAR1 and PAR4, and these intracellular events were very similar to those observed in platelets shown in previous studies. We developed a novel image-based assay to quantitatively measure the morphological changes in living cells, and observed the underlying mechanism for PAR1- and PAR4-mediated morphological changes in MEG-01 cells. Selective inhibition of PAR1 and PAR4 by vorapaxar and BMS-986120, respectively, showed that thrombin-induced morphological changes were primarily mediated by PAR4 activation. Treatment of a set of kinase inhibitors and 2-aminoethoxydiphenyl borate (2-APB) revealed that thrombin-mediated morphological changes were primarily regulated by calcium-independent pathways and PAR4 activation-induced PI3K/Akt and RhoA/ROCK signaling pathways in MEG-01 cells. These results indicate the importance of PAR4-mediated signaling pathways in thrombin-induced morphological changes in MEG-01 cells and provide a useful in vitro cellular model for platelet research.


Assuntos
Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Trombina/metabolismo , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Plaquetas/metabolismo , Cálcio/metabolismo , Linhagem Celular , Imunofluorescência , Expressão Gênica , Humanos , Megacariócitos/citologia , Megacariócitos/metabolismo , Modelos Biológicos , Trombina/metabolismo
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