RESUMO
Anti-cluster of differentiation (CD) 3 × α programmed death-ligand 1 (PD-L1) bispecific T-cell engager (BsTE)-bound T-cells (BsTE:T) are a promising new cancer treatment agent. However, the mechanisms of action of bispecific antibody-armed activated T-cells are poorly understood. Therefore, this study aimed to investigate the anti-tumor mechanism and efficacy of BsTE:T. The BsTE:T migration was assessed in vivo and in vitro using syngeneic and xenogeneic tumor models, flow cytometry, immunofluorescence staining, transwell migration assays, microfluidic chips, Exo View R100, western blotting, and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technology. In murine B16 melanoma, MC38 colon cancer, and human multiple myeloma cells, BsTE:T exhibited superior tumor elimination relative to that of T-cells or BsTE alone. Moreover, BsTE:T migration into tumors was significantly enhanced owing to the presence of PD-L1 in tumor cells and secretion of PD-L1-containing exosomes. Furthermore, increased infiltration of CD44highCD62Llow effector memory CD8+ T-cells into tumors was closely associated with the anti-tumor effect of BsTE:T. Therefore, BsTE:T is an innovative potential anti-tumor therapy, and exosomal PD-L1 plays a crucial role both in vitro and in vivo in the anti-tumor activity of BsTE:T.
Assuntos
Anticorpos Biespecíficos , Antígeno B7-H1 , Exossomos , Animais , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Exossomos/metabolismo , Exossomos/imunologia , Camundongos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Humanos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Camundongos Endogâmicos C57BL , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Complexo CD3/imunologia , Complexo CD3/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linhagem Celular Tumoral , Feminino , Movimento Celular , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Bronchus-associated lymphoid tissue (BALT) is a rare cause of extranodal marginal zone lymphoma (MZL). Although most patients with BALT lymphoma (BALToma) show an indolent clinical course and are monitored without treatment, there are limited real-world data on the long-term outcome of "watch-and-wait' strategy in comparison with other treatments. The survival outcomes of patients newly diagnosed with BALToma at three tertiary hospitals in Korea undergoing two treatment strategies were analyzed: group A, patients who were monitored without any treatment or received only radiotherapy after diagnosis; and group B, patients receiving any kind of systemic chemotherapy after diagnosis, regardless of their history of any local treatment such as surgery or radiotherapy. Of the 67 patients included in our analysis, the 10-year progression-free survival (PFS) and 10-year overall survival (OS) rates were 65.3% and 83.2%, respectively. The 10-year PFS rates for observation or localized treatment and systemic chemotherapy were 78.7% and 56.9%, respectively (p = 0.044). Ten-year OS rates for observation or localized treatment and systemic chemotherapy were 100% and 71.7%, respectively (p = 0.016). Multivariate analysis showed that bilateral lung (HR 2.462, p = 0.047) and extrapulmonary organ (HR 4.485, p = 0.004) involvement were the only significant factors associated with poor PFS. Prognostic factor analysis for OS did not yield significant results. Patients with BALToma show a favorable prognosis, suggesting that observation or localized therapy alone may be effective for patient management. However, patients with bilateral lung or extrapulmonary involvement may require careful monitoring for disease progression and more aggressive treatment approaches.
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Linfoma de Zona Marginal Tipo Células B , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma de Zona Marginal Tipo Células B/mortalidade , República da Coreia/epidemiologia , Idoso , Adulto , Conduta Expectante , Taxa de Sobrevida , Neoplasias Brônquicas/terapia , Neoplasias Brônquicas/mortalidade , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Intervalo Livre de DoençaRESUMO
PURPOSE: Loneliness is a risk factor for mental and physical disorders. Rapid individualization, with increasing associated social burden, is a contributing factor to loneliness among Koreans. This study aimed to investigate the relationship between loneliness and mental disorders, as well as to determine whether long-term loneliness is a factor predicting the occurrence of mental disorders in adults. METHODS: The National Mental Health Survey of Korea 2021, a nationally representative survey on mental disorders, was conducted. Responses from 5511 participants were collected using the Korean version of the Composite International Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders fourth edition, Structured Clinical Interview for Internet Gaming Disorder, and the World Health Organization Adult Attention-deficit Hyperactivity Disorder (ADHD) self-report scale. Loneliness and its duration were investigated among these participants. RESULTS: Loneliness was reported by approximately 2.9% of the general population. Loneliness was associated with an increased adulthood prevalence of alcohol use disorders, nicotine use disorders, depressive disorders, anxiety disorders, adult ADHD, and internet gaming disorders. Long-term loneliness was significantly associated with an elevated risk of alcohol use disorders, nicotine use disorders, depressive disorders, and anxiety disorders. Internet gaming disorder was associated with loneliness lasting > 1 year. CONCLUSION: Various adult psychiatric disorders were associated with loneliness. The significant dose-effect relationship indicated the importance of early detection of and intervention for loneliness to reduce its negative consequences on mental health.
Assuntos
Inquéritos Epidemiológicos , Solidão , Transtornos Mentais , Humanos , Solidão/psicologia , República da Coreia/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Fatores de Risco , Prevalência , Adulto Jovem , Saúde Mental/estatística & dados numéricos , Idoso , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtorno de Adição à Internet/epidemiologia , Transtorno de Adição à Internet/psicologiaRESUMO
BACKGROUND: Lichen striatus (LS) is an acquired skin disorder with a linear pattern along Blaschko's lines. It commonly occurs in childhood, and the lesions spontaneously regress within several months. OBJECTIVES: Although up to 50% of LS cases exhibit hypopigmentation that can persist for several months to years, it is unknown why LS is associated with such a high incidence of hypopigmentation compared to other inflammatory skin diseases. Therefore, this study aimed to analyse the differences in the skin microbiome between LS patients with and without hypopigmentation. METHODS: Differences in skin microbiome were analysed using whole genome sequencing of skin biopsies and subsequent bioinformatics analyses. RESULTS: Some microbes commonly found in hypopigmented skin disorders, including Cutibacterium acnes, were more abundant in patients with LS showing hypopigmentation than in those not showing hypopigmentation. CONCLUSIONS: The skin microbiota may be involved in the development of hypopigmentation in LS and may be considered a treatment target to reduce LS duration and hypopigmentation.
Assuntos
Hipopigmentação , Microbiota , Humanos , Hipopigmentação/microbiologia , Feminino , Masculino , Adulto , Pele/microbiologia , Pele/patologia , Criança , Adolescente , Pessoa de Meia-Idade , Adulto Jovem , Erupções Liquenoides/microbiologiaRESUMO
Alzheimer's disease (AD) is a neurodegenerative disease with multifactorial pathogenesis. However, most current therapeutic approaches for AD target a single pathophysiological mechanism, generally resulting in unsatisfactory therapeutic outcomes. Recently, mesenchymal stem cell (MSC) therapy, which targets multiple pathological mechanisms of AD, has been explored as a novel treatment. However, the low brain retention efficiency of administered MSCs limits their therapeutic efficacy. In addition, autologous MSCs from AD patients may have poor therapeutic abilities. Here, we overcome these limitations by developing iron oxide nanoparticle (IONP)-incorporated human Wharton's jelly-derived MSCs (MSC-IONPs). IONPs promote therapeutic molecule expression in MSCs. Following intracerebroventricular injection, MSC-IONPs showed a higher brain retention efficiency under magnetic guidance. This potentiates the therapeutic efficacy of MSCs in murine models of AD. Furthermore, human Wharton's jelly-derived allogeneic MSCs may exhibit higher therapeutic abilities than those of autologous MSCs in aged AD patients. This strategy may pave the way for developing MSC therapies for AD.
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Doença de Alzheimer , Células-Tronco Mesenquimais , Doenças Neurodegenerativas , Geleia de Wharton , Humanos , Camundongos , Animais , Idoso , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Nanopartículas Magnéticas de Óxido de Ferro , Diferenciação CelularRESUMO
The association between psoriasis and alcohol consumption has been inconsistent across various studies. However, to the best of our knowledge, no dose-response meta-analysis has been performed to date. This study aims to investigate the association between alcohol consumption and psoriasis. The search was performed on July 27, 2021, using Embase and MEDLINE. The restricted cubic spline analysis was used to perform a dose-response analysis. We identified 3,904 studies, of which 48 studies with 1,702,847 individuals across 24 countries were included. Alcohol consumption was positively associated with psoriasis (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.27-1.70). In addition, a significantly increased OR for psoriasis was observed in males (OR, 1.84; 95% CI, 1.13-3.01) but not in females (OR, 1.22; 95% CI, 0.97-1.54). Based on eight studies, including three cohort and five case-control studies, the analysis revealed that with each additional gram of daily alcohol intake, the OR for psoriasis increased by 4%. We found a positive association between alcohol consumption and psoriasis. The association is more prominent in the group drinking more than 45 g of alcohol per day (3.2 alcoholic drink equivalent).
Assuntos
Consumo de Bebidas Alcoólicas , Psoríase , Psoríase/epidemiologia , Humanos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Feminino , Masculino , Fatores de Risco , Fatores Sexuais , Relação Dose-Resposta a DrogaRESUMO
Background: Cytomegalovirus (CMV) reactivation is a common complication in patients undergoing allogeneic stem cell transplantation. However, the incidence of CMV reactivation is low after autologous stem cell transplantation (auto-SCT), and the prognostic value of CMV reactivation remains controversial. Moreover, reports on late CMV reactivation after auto-SCT are limited. We aimed to analyze the association between CMV reactivation and survival outcomes and develop a predictive model for late CMV reactivation in patients undergoing auto-SCT. Methods: Data of 201 patients who underwent SCT at the Korea University Medical Center from 2007 to 2018 were collected. We analyzed prognostic factors for survival outcomes after auto-SCT and risk factors for late CMV reactivation using a receiver operating characteristic curve. Then, we developed a predictive risk model for late CMV reactivation based on results of the risk factor analysis. Results: Early CMV reactivation was significantly associated with better overall survival (OS) (hazard ratio [HR], 0.329; P = 0.045) in patients with multiple myeloma; however, no significant differences were observed in patients with lymphoma. For late CMV reactivation, a serum lactate dehydrogenase level greater than the upper limit of normal (HR, 2.251; P = 0.027) and late CMV reactivation (HR, 2.964; P = 0.047) were independent risk factors for poor OS, while lymphoma diagnosis (vs. multiple myeloma; HR, 0.389; P = 0.016) was an independent risk factor for good OS. In risk factor analysis for late CMV reactivation, T-cell lymphoma diagnosis (odds ratio [OR], 8.499; P = 0.029), ≥ two prior chemotherapies (OR, 8.995; P = 0.027), failure to achieve complete response (CR) after transplantation (OR, 7.124; P = 0.031), and early CMV reactivation (OR, 12.853; P = 0.007) were significantly associated with late CMV reactivation. To develop the predictive risk model for late CMV reactivation, a score (1 to 1.5) was assigned for each of the above-mentioned variables. The optimal cutoff value (1.75 points) was calculated using the receiver operating characteristic curve. The predictive risk model showed good discrimination, with an area under the curve of 0.872 (standard error, 0.062; P < 0.001). Conclusions: Late CMV reactivation was an independent risk factor for inferior OS, whereas early CMV reactivation was associated with better survival in patients with multiple myeloma. This risk prediction model could be helpful in identifying high-risk patients who require monitoring for late CMV reactivation and potentially benefit from prophylactic or preemptive therapy.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Linfoma , Mieloma Múltiplo , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Citomegalovirus , Mieloma Múltiplo/terapia , Infecções por Citomegalovirus/etiologia , Transplante Autólogo/efeitos adversos , Prognóstico , Linfoma/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Patients with long-standing psoriasis who are not treated with conventional medicine seek complementary and alternative medicine (CAM). The biological revolution in the field of psoriasis since the late 2000s has progressed, expecting clearance or almost clearance of the disease. The frequency and type of CAM usage may have changed after these advances. We aimed to investigate changes in CAM use in Korean patients with psoriasis before and after the prevalent use of biologics. METHODS: Patients with psoriasis who visited Pusan National University Hospitals (Busan and Yangsan) between March 2020 and June 2022 were made to complete a face-to-face structured questionnaire. These results were compared with our previous study conducted approximately 10 years ago. RESULTS: In total, 207 patients were included. Compared with the previous results, the frequency of CAM use (67.6%) increased (P < 0.001). Oriental medicine (67.1%) has most commonly been used, followed by health supplements and bath therapy. The biggest reason for using CAM was "to try all the potential treatments." Meanwhile, negative concerns about conventional medicine (13.5%) significantly decreased during the 10-year period (P < 0.001). CONCLUSION: Although treatment efficacy has increased with biologics development, CAM usage remains prevalent among Korean patients with psoriasis. Therefore, dermatologists need more efforts to improve patients' understanding of conventional medicine, including biologics.
Assuntos
Produtos Biológicos , Terapias Complementares , Psoríase , Humanos , Terapias Complementares/métodos , Inquéritos e Questionários , Psoríase/tratamento farmacológico , República da Coreia , Produtos Biológicos/uso terapêuticoRESUMO
BACKGROUND: Although it is known that a substantial proportion of the population experience loneliness, the consequence of loneliness remains unclear by countries and ages. Accordingly, this study aimed to assess the association between loneliness and suicidality in the general population of Korea. METHOD: A total of 5,511 Koreans aged 18-79 completed a tablet-assisted personal interview using the Korean version of the Composite International Diagnostic Interview and responded to questions about loneliness and lifetime suicidal ideation, plans, and attempts. A logistic regression analysis was used to examine the association between loneliness and suicidality. RESULTS: Approximately one-third of the Korean general population reported loneliness. Being older, never married, widowed, separated, or divorced, unemployed, and having a part-time job were all significantly related to loneliness. After adjusting for sociodemographic factors, individuals with loneliness were significantly associated with increased suicidal ideation (adjusted odd ratio [aOR], 4.05; 95% confidence interval [CI], 3.36-4.88), suicidal plans (aOR, 4.91; 95% CI, 3.34-7.21), and suicidal attempts (aOR, 4.82; 95% CI, 3.03-7.66). Even after adjusting for sociodemographic factors and mental disorders, suicidality remained statistically significant. Moreover, frequent, moderate-to-severe, and long-term loneliness were all associated with increased ORs for suicidality, regardless of sociodemographic factors and mental disorders. CONCLUSION: Loneliness was associated with suicidal ideation, plans, and attempts. This study lays the foundation for public health policymakers to establish early intervention and mental health care support for lonely people.
Assuntos
Ideação Suicida , Suicídio , Humanos , Prevalência , Solidão , República da Coreia/epidemiologiaRESUMO
PURPOSE: Congenital heart disease (CHD) is divided into two groups according to cyanosis status. Cyanotic CHD has a low level of systemic oxygenation and is accompanied by increased erythropoiesis. We hypothesized that pediatric patients with CHD would exhibit different thromboelastographic profiles according to their cyanosis status. METHODS: The study recruited 70 pediatric patients younger than 12 months who were undergoing surgery for CHD. Patients were allocated to the acyanotic group or cyanotic group after preoperative evaluations of their diagnosis and peripheral oxygen saturation in the operating room on room air. After inducing anesthesia, blood samples were collected. Hematologic and thromboelastographic profiles were evaluated. RESULTS: Demographic data were similar between groups. The thromboelastographic profiles did not differ significantly between the groups. Hematologic profiles generally did not significantly differ between groups, except hematocrit (Hct) was higher in the cyanotic group (41.7 ± 6.8% vs. 35.3 ± 5.3%, p < 0.001). In patients under 3 months of age, prothrombin time (PT) (cyanotic group 15.4 ± 1.1 s vs. acyanotic group 14.2 ± 2.4 s, p = 0.02) and international normalized ratio (INR) (cyanotic group 1.24 ± 0.12 vs. acyanotic group 1.12 ± 0.27, p = 0.01) were significantly greater in the cyanotic group. CONCLUSION: There were no differences in thromboelastographic profiles between the patients with or without cyanosis, regardless of age. The Hct was higher in the cyanotic group in patients under 12 months, while the PT was prolonged and the INR was increased in the cyanotic group in patients under 3 months.
Assuntos
Cardiopatias Congênitas , Humanos , Criança , Cardiopatias Congênitas/cirurgia , Cianose/complicações , Cianose/cirurgia , Tromboelastografia , Testes de Coagulação Sanguínea , Hipóxia/complicaçõesRESUMO
Programmed death-ligand 1 (PD-L1) is constitutively expressed by hypoxia-inducible factor 2α (HIF2α). It can be induced by interferon gamma (IFNγ) signaling in clear cell renal cell carcinoma (ccRCC). Clinical trials of metastatic ccRCCs have suggested that a canonical IFNγ signature is a better biomarker for therapeutic response to immune checkpoint inhibitors (ICIs) than PD-L1 expression levels in tumor cells. To understand the therapeutic response to ICIs according to PD-L1 expression levels, we analyzed transcriptional regulation of the PD-L1 promoter by HIF2α and IFNγ-inducible interferon regulatory factor-1 (IRF-1) in ccRCC cells. Here, we present two ccRCC cell models showing differential PD-L1 expression levels in response to IFNγ and hypoxia. Analysis of The Cancer Genome Atlas RNA-sequencing data revealed that PD-L1 expression correlated with JAK2 and STAT1 expression of the canonical IFNγ signature in ccRCC tissues. Upon IFNγ stimulation, PD-L1 was induced by sequential activation of JAK2/STAT1/IRF-1 signaling in both WT- and Mut- VHL ccRCC cells. IFNγ activated the IRF-1α site of the PD-L1 promoter. The IFNγ-mediated increase of PD-L1 expression in Mut-VHL cells was 4.8-fold greater than that in WT-VHL cells. Under normoxia condition, PD-L1 expression in Mut-VHL cells was significantly higher than that in WT-VHL cells due to high basal HIF2α expression. Under hypoxia condition, PD-L1 expression in WT-VHL cells was induced up to 1.8-fold through activation of hypoxia-response elements 2 and 3. In contrast, although PD-L1 in Mut-VHL cells was already highly expressed in the basal state through activation of hypoxia-response elements 2, 3, and 4, it was no longer induced by hypoxia. In conclusion, Mut-VHL ccRCC cells displayed higher PD-L1 expression due to high basal HIF2α expression and a stronger response to IFNγ stimulation than WT-VHL cells. The fact that HIF2α antagonists can potentially reduce PD-L1 expression levels should be considered in ICI combination therapy.
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Carcinoma de Células Renais , Neoplasias Renais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia , Interferon gama/metabolismo , Neoplasias Renais/metabolismo , Masculino , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismoRESUMO
The unique biological characteristics and promising clinical potential of extracellular vesicles (EVs) have galvanized EV applications for regenerative medicine. Recognized as important mediators of intercellular communication, naturally secreted EVs have the potential, as innate biotherapeutics, to promote tissue regeneration. Although EVs have emerged as novel therapeutic agents, challenges related to the clinical transition have led to further functionalization. In recent years, various engineering approaches such as preconditioning, drug loading, and surface modification have been developed to potentiate the therapeutic outcomes of EVs. Also, limitations of natural EVs have been addressed by the development of artificial EVs that offer advantages in terms of production yield and isolation methodologies. In this review, an updated overview of current techniques is provided for the functionalization of natural EVs and recent advances in artificial EVs, particularly in the scope of regenerative medicine.
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Vesículas Extracelulares , Medicina Regenerativa , Transporte Biológico , Vesículas Extracelulares/metabolismo , Medicina Regenerativa/métodosRESUMO
Patients with chronic itch describe their pruritus in a wide variety of ways. However, these subjective descriptions are often not taken into consideration by physicians. This study aimed to validate patients' descriptions of pruritus, and to investigate the relationship between various descriptions of pruritus and the patient burden of chronic pruritus by examining the mediating effects of sleep disturbance and sexual dysfunction on patient's quality of life, as predicted by various descriptions of pruritus. Exploratory and confirmatory factor analyses were performed to identify the factor structure measured by 11 descriptions of pruritus. The study then analysed differences in the degree of sleep disturbance, sexual dysfunction, and quality of life deterioration factors using a structural equation modelling method. Using data from 419 patients with chronic pruritus, 11 descriptions of pruritus were classified into 2 groups: (i) sensory pruritus (i.e. stinging, stabbing, burning, painful, formication, throbbing, and cold) that are linked with descriptions of pruritus patterns; and (ii) affective pruritus (i.e. annoying, unbearable, worrisome, and warm) from patient reports of psychological or emotional distress. The study found that affective pruritus decreases patient's quality of life either directly or indirectly through sleep disturbance. In conclusion, clues about a patients' sleep disturbance or poor quality of life can be obtained through their descriptions of pruritus.
Assuntos
Qualidade de Vida , Transtornos do Sono-Vigília , Humanos , Análise de Classes Latentes , Prurido/diagnóstico , Prurido/psicologia , Transtornos do Sono-Vigília/diagnóstico , Parestesia , DorRESUMO
OBJECTIVES: The objective of this study was to evaluate the efficacy of cell therapy using human amniotic epithelial stem cells (hAESCs) for the treatment of premature rupture of membranes (PROM) in vitro. DESIGN: Using the amniotic pore culture technique (APCT), we mimicked the environment of PROM in vitro, thus enabling the observation of the healing process of hAESC-treated amniotic membranes. MATERIALS: Amniotic membrane samples were collected from placentas of pregnant women who underwent elective cesarean sections. APCT model and isolated hAESCs were used in this study. All patients who participated in this study provided their written informed consent prior to the commencement of the study. SETTINGS: To create the APCT model in vitro, isolated amniotic membranes were punched to create 5 mm diameter circles and re-punched to form a 1-mm pore at the center. Membranes were cultured in α-minimal essential medium, and the hAESCs were collected and cultured as well. Subsequently, the APCT models were divided into two groups: hAESC treated and control. METHODS: Within the culture period, pore sizes were calculated to evaluate the degree of tissue regeneration in both groups. We then evaluated the histology, cell density, and epithelial thickness of the regenerated tissues. Statistical analyses were performed using SPSS software ver. 20.0 (IBM, Armonk, NY, USA) with repeated-measures one-way analysis of variance or paired samples t test. The significance level was set at p < 0.05. RESULTS: As per the evaluation of the APCT model in vitro, the pore size in the hAESC-treated group reduced by 62.2% on day 6 (62.2 ± 0.19, n = 24), whereas in the control group, it shrank by only 36.8% (p < 0.05) (36.8 ± 0.19, n = 24). Furthermore, the epithelial thickness in the amniotic epithelial stem cell-treated group (10.08 ± 1.26 µm, n = 8) was significantly higher than that in the control group (5.87 ± 0.94 µm, n = 8). Cell density in the regenerated tissue in the amniotic epithelial stem cell-treated group (57 ± 2.77, n = 8) was significantly higher than that in the control group (49 ± 2.23, n = 8). LIMITATIONS: In this study, we did not explore the molecular mechanisms by which hAESCs participate in membrane healing in the APCT model. Although our results showed a significant difference, this difference was not too obvious. Therefore, further research on the mechanisms of hAESCs is needed, with more amniotic tissues and APCT samples being tested. CONCLUSIONS: We developed an APCT model to investigate the PROM conditions in vitro. By implanting donor hAESCs in the pores of the APCT model, we observed that hAESCs seeding accelerated pore healing in vitro. Thus, hAESCs may be a valuable source of cells for cell therapies in regenerative medicine.
Assuntos
Ruptura Prematura de Membranas Fetais , Nascimento Prematuro , Recém-Nascido , Humanos , Feminino , Gravidez , Âmnio , Transplante de Células-Tronco , Técnicas de Cultura , Ruptura Prematura de Membranas Fetais/terapia , Líquido AmnióticoRESUMO
Severe cardiac damage following myocardial infarction (MI) causes excessive inflammation, which sustains tissue damage and often induces adverse cardiac remodeling toward cardiac function impairment and heart failure. Timely resolution of post-MI inflammation may prevent cardiac remodeling and development of heart failure. Cell therapy approaches for MI are time-consuming and costly, and have shown marginal efficacy in clinical trials. Here, nanoparticles targeting the immune system to attenuate excessive inflammation in infarcted myocardium are presented. Liposomal nanoparticles loaded with MI antigens and rapamycin (L-Ag/R) enable effective induction of tolerogenic dendritic cells presenting the antigens and subsequent induction of antigen-specific regulatory T cells (Tregs). Impressively, intradermal injection of L-Ag/R into acute MI mice attenuates inflammation in the myocardium by inducing Tregs and an inflammatory-to-reparative macrophage polarization, inhibits adverse cardiac remodeling, and improves cardiac function. Nanoparticle-mediated blocking of excessive inflammation in infarcted myocardium may be an effective intervention to prevent the development of post-MI heart failure.
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Insuficiência Cardíaca , Infarto do Miocárdio , Nanopartículas , Animais , Modelos Animais de Doenças , Insuficiência Cardíaca/prevenção & controle , Inflamação , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/complicações , MiocárdioRESUMO
Nanoparticles have been used for effectively delivering imaging agents and therapeutic drugs into stem cells. However, nanoparticles are not sufficiently internalized into stem cells; thus, new delivery method of nanoparticles into stem cells is urgently needed. Herein, we develop bicyclo[6.1.0]nonyne (BCN)-conjugated gold nanoparticles (BCN-AuNPs), which can be bioorthogonally conjugated to azide (-N3) groups on the surface of metabolically engineered stem cells via bioorthogonal click chemistry. For incorporating azide groups on the cell surface, first, human adipose-derived mesenchymal stem cells (hMSCs) were metabolically engineered with N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz). Second, clickable BCN-AuNPs were bioorthogonally conjugated to azide groups on Ac4ManNAz-treated hMSCs. Importantly, a large amount of BCN-AuNPs was specifically conjugated to metabolically engineered hMSCs and then internalized rapidly into stem cells through membrane turnover mechanism, compared to the conventional nanoparticle-derived endocytosis mechanism. Furthermore, BCN-AuNPs entrapped in endosomal/lysosomal compartment could escape efficiently to the cytoplasm of metabolically engineered stem cells. Finally, BCN-AuNPs in stem cells were very safe, and they did not affect stem cell functions, such as self-renewal and differentiation capacity. These bioorthogonally conjugated nanoparticles on metabolically engineered stem cells can enhance the cellular uptake of nanoparticles via bioorthogonal conjugation mechanism.
Assuntos
Células-Tronco Mesenquimais/metabolismo , Nanopartículas Metálicas/química , Endocitose , Ouro/química , HumanosRESUMO
BACKGROUND: The precise diagnosis of dermoid cysts, which are usually located deeper than other common cysts, is important because dermoid cysts occasionally recur after incomplete excision. Ultrasonography (US) could give useful preoperative information of dermoid cysts but only a few studies have been conducted on US findings related to dermoid cysts. This study aimed to investigate clinical and US findings on pediatric dermoid cysts. METHODS: We retrospectively reviewed the medical records, clinical photographs, and US findings of 31 pediatric patients (≤18 years of age) with histopathologically diagnosed dermoid cysts who visited the Pusan National University Hospital between 2007 and 2016. RESULTS: Of the 31 patients, 25 underwent ultrasonography. The mean long diameter, short diameter, and depth of the cysts were 12.7, 9.0, and 3.8 mm, respectively. Sixteen cysts (64%) were ovoid, 23 (92%) showed hypoechogenicity, 20 (80%) showed heterogeneity, 19 (76%) showed well-demarcated outer margins, and all cysts showed positive posterior acoustic enhancement. All cysts extended to the subcutaneous tissue, and 15 (60%) showed a connection with the underlying muscle. CONCLUSIONS: Ultrasonography may be a useful diagnostic method to visualize the extent and location of the dermoid cyst and make an accurate diagnosis prior to surgical intervention.
Assuntos
Cisto Dermoide , Criança , Cisto Dermoide/diagnóstico por imagem , Cisto Dermoide/cirurgia , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , UltrassonografiaRESUMO
BACKGROUND: This study investigated trends in the prevalence of major depressive disorder (MDD) by sociodemographic factors in South Korea. METHODS: National samples of the general population aged 18 years or older collected from the nationwide Korean Epidemiologic Catchment Area surveys conducted in 2001 (n = 6,206), 2006 (n = 6,466), and 2011 (n = 5,986) were used. For MDD diagnosis, we conducted face-to-face interviews using the Korean version of the Composite International Diagnostic Interview. We performed logistic regression analyses stratified by gender, after adjusting for other sociodemographic variables, to calculate the 2006-to-2001 odds ratio (OR) and 2011-to-2001 OR by subgroups of sociodemographic factors to explore the association of MDD prevalence with sociodemographic factors over time. RESULTS: The prevalence of MDD in the general population of South Korea increased steadily from 2001, to 2006, and to 2011 (1.6%, 2.5%, and 3.1%, respectively). Among the men, the prevalence of MDD continued to increase significantly in 18-29 years of age group (2006: adjusted OR [AOR], 3.32; 2011: AOR, 7.42), at-risk drinking group (2006: AOR, 3.56; 2011: AOR, 4.77), and not living with a partner group (2006: AOR, 3.24; 2011: AOR, 3.25). Meanwhile, among the women, the prevalence of MDD continued to significantly increase in the below-average household income group (2006: AOR, 2.58; 2011: AOR, 2.59), at-risk drinking group (2006: AOR, 2.02; 2011: AOR, 2.47), and unemployed group (2006: AOR, 1.48; 2011: AOR, 2.04). CONCLUSION: This study may provide significant information for public policymakers to allocate sufficient health resources on MDD to vulnerable groups, particularly, men aged 18-29 years and women living in households with below-average income, and for clinicians to develop appropriate screening and treatment modalities for MDD.
Assuntos
Transtorno Depressivo Maior/epidemiologia , Fatores Sociodemográficos , Adolescente , Adulto , Consumo de Bebidas Alcoólicas , Transtorno Depressivo Maior/diagnóstico , Feminino , Inquéritos Epidemiológicos , Humanos , Renda , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Fatores Sexuais , Desemprego , Adulto JovemRESUMO
BACKGROUND: Although childhood maltreatment is a known risk factor for adulthood mental health, the impact of different types of childhood maltreatment on mental disorders is not yet clear. This study explored the association of each type of childhood maltreatment with adulthood mental disorders and suicidality in South Korea. METHODS: A total of 5,102 individuals from the general populations over the age of 18 responded to the Korean version of the Composite International Diagnostic Interview and questions about childhood maltreatment (emotional neglect, psychological abuse, physical abuse, and sexual abuse). To evaluate the odds ratio for mental disorders and suicidality associated with each type of childhood maltreatment, we used logistic regression analysis. RESULTS: About 17.0% of the respondents reported having experienced a type of maltreatment in childhood. According to the type, 9.4% reported physical abuse, 9.3% reported emotional neglect, 7.9% reported psychological abuse, and 3.8% reported sexual abuse. Exposure to each type of childhood maltreatment was associated with most types of mental disorders after adjusting for sociodemographic factors. Each type of childhood maltreatment victim was associated with suicidality (suicidal ideations, suicide plans, and suicide attempts). Dose-response patterns for suicide attempts were observed in all types of victims. Moreover, the respondents who experienced frequent childhood emotional neglect were 14 times more likely to have attempted suicide. CONCLUSION: Childhood maltreatment was associated with mental health in adulthood. The findings show the need for early detection and intervention of victims of childhood maltreatment to minimize its negative impact on adult mental health.
Assuntos
Maus-Tratos Infantis , Transtornos Mentais/diagnóstico , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Criança , Maus-Tratos Infantis/estatística & dados numéricos , Abuso Sexual na Infância/estatística & dados numéricos , Abuso Emocional/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Razão de Chances , Abuso Físico/estatística & dados numéricos , República da Coreia , Ideação Suicida , Suicídio/psicologia , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: A poroma typically presents as a solitary, pink-to-red papule or nodule in acral volar areas. However, in nonvolar areas, this typical clinical feature (TCF) can be difficult to identify. OBJECTIVE: We aimed to compare clinical and dermoscopic characteristics between nonvolar poroma (NVP) and volar (ie, typical) poroma (VP). METHODS: We assessed the clinical and dermoscopic characteristics of 40 patients with poromas who were divided into the NVP and VP groups. RESULTS: Of the 40 patients, 20 (50.0%) were allocated to the NVP group and 20 (50.0%) to the VP group. Pigmented variants were more common in the NVP group than in the VP group (60.0% vs 5.0%). The TCF of poroma was observed less frequently in the NVP than the VP group (45.0% vs 85.0%). Approximately one-third (30.0%) of patients with NVP received an initial clinical diagnosis of skin cancer. Dermoscopic patterns associated with melanoma or basal cell carcinoma were more common in the NVP group than in the VP group (65% vs 30%). CONCLUSIONS: Skin cancer-associated clinicodermoscopic features were more frequently observed in patients with NVP, who simultaneously lost dermoscopic patterns associated to poromas and acquired those associated with skin cancer, than those with VP.