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OBJECTIVES: To compare microvascular flow imaging (MVFI) and power Doppler ultrasonography imaging (PDUS) for detecting intratumoral vascularity in recurrent thyroid cancer both before and after radiofrequency ablation (RFA). METHODS: This retrospective study included 80 patients (age, 57 ± 12 years; 54 women) with 110 recurrent tumors who underwent RFA between January 2021 and June 2023. A total of 151 PDUS and MVFI image sets were analyzed (85 pre-RFA, 66 post-RFA). Two readers assessed vascularity on the images using a four-point scale with a 2-week interval between PDUS and MVFI to estimate inter-reader agreement. Intra-reader agreement was determined by reinterpreting images in reverse order (MVFI-PDUS) after a 1-month gap. Additionally, diagnostic performance for identifying viable tumors after RFA was assessed in 44 lesions using thyroid-protocol CT as a reference standard. RESULTS: MVFI demonstrated higher vascular grades than PDUS, both before (reader 1: 3.04 ± 1.15 vs. 1.93 ± 1.07, p < 0.001; reader 2: 3.20 ± 0.96 vs. 2.12 ± 1.07, p < 0.001) and after RFA (reader 1: 2.44 ± 1.28 vs. 1.67 ± 1.06, p < 0.001; reader 2: 2.62 ± 1.23 vs. 1.83 ± 0.99, p < 0.001). Inter-reader agreement was substantial (κ = 0.743) and intra-reader agreement was almost perfect (κ = 0.840). MVFI showed higher sensitivity (81.5%-88.9%) and accuracy (84.1%-86.4%) than PDUS (sensitivity: 51.9%, p < 0.01; accuracy: 63.6-70.5%, p < 0.04), without sacrificing specificity. CONCLUSION: MVFI was superior to PDUS for assessing intratumoral vascularity and showed good inter- and intra-reader agreement, highlighting its clinical value for assessing pre-RFA vascularity and accurately identifying post-RFA viable tumors in recurrent thyroid cancer. CLINICAL RELEVANCE STATEMENT: Microvascular flow imaging (MVFI) is superior to power-Doppler US for assessing intratumoral vascularity; therefore, MVFI can be a valuable tool for assessing vascularity before radiofrequency ablation (RFA) and for identifying viable tumors after RFA in patients with recurrent thyroid cancer. KEY POINTS: The value of microvascular flow imaging (MVFI) for evaluating intratumoral vascularity is unexplored. MVFI demonstrated higher vascular grades than power Doppler US before and after ablation. Microvascular flow imaging showed higher sensitivity and accuracy than power Doppler US without sacrificing specificity.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown etiology. The aim of this study was to evaluate the environmental and occupational risk factors of IPF. METHODS: This hospital-based, case-control study included 206 patients with IPF selected from the Seoul National University Bundang Hospital Interstitial Lung Disease registry and 167 controls without lung disease. Data on occupation, lifestyle, transportation, and types of environmental and occupational dust exposure were obtained using a questionnaire. IPF diagnosis was confirmed based on the recent guidelines, and the possibility of hypersensitivity pneumonitis was excluded. Multiple logistic regression was performed to determine the risk factors for IPF. RESULTS: After adjusting for age and sex, ever-smokers (odds ratio [OR], 2.35; 95 % confidence interval [CI]: 1.51-3.68) and individuals who smoked more than 30 pack-years (OR, 2.79; 95%CI: 1.70-4.68) showed an increased risk for IPF. Any occupational dust exposure (adjusted OR, 2.08; 95%CI: 1.19-3.72), especially exposure to chemicals (adjusted OR, 3.52; 99%CI: 1.56-9.05), was associated with IPF after adjusting for age, sex, and smoking. CONCLUSIONS: Smoking and occupational dust exposure are associated with an increased risk for IPF. Both factors have dose and duration-dependent relationships with the risk for IPF.
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Poeira , Fibrose Pulmonar Idiopática , Exposição Ocupacional , Fumar , Humanos , Fibrose Pulmonar Idiopática/etiologia , Fibrose Pulmonar Idiopática/epidemiologia , Estudos de Casos e Controles , Exposição Ocupacional/efeitos adversos , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fumar/efeitos adversos , Exposição Ambiental/efeitos adversos , Inquéritos e QuestionáriosRESUMO
Background: Ovarian cancer is one of women's malignancies with the highest mortality among gynecological cancers. Paclitaxel is used in first-line ovarian cancer chemotherapy. Research on paclitaxel-resistant ovarian cancer holds significant clinical importance. Methods: Cell viability and flow cytometric assays were conducted at different time and concentration points of deguelin and paclitaxel treatment. Immunoblotting was performed to assess the activation status of key signaling molecules important for cell survival and proliferation following treatment with deguelin and paclitaxel. The fluo-3 acetoxymethyl assay for P-glycoprotein transport activity assay and cell viability assay in the presence of N-acetyl-L-cysteine were also conducted. Results: Cell viability and flow cytometric assays demonstrated that deguelin resensitized paclitaxel in a dose- and time-dependent manner. Cotreatment with deguelin and paclitaxel inhibited EGFR and its downstream signaling molecules, including AKT, ERK, STAT3, and p38 MAPK, in SKOV3-TR cells. Interestingly, cotreatment with deguelin and paclitaxel suppressed the expression level of EGFR via the lysosomal degradation pathway. Cotreatment did not affect the expression and function of P-glycoprotein. N-acetyl-L-cysteine failed to restore cell cytotoxicity when used in combination with deguelin and paclitaxel in SKOV3-TR cells. The expression of BCL-2, MCL-1, and the phosphorylation of the S155 residue of BAD were downregulated. Moreover, inhibition of paclitaxel resistance by deguelin was also observed in HeyA8-MDR cells. Conclusion: Our research showed that deguelin effectively suppresses paclitaxel resistance in SKOV3-TR ovarian cancer cells by downregulating the EGFR and its downstream signaling pathway and modulating the BCL-2 family proteins. Furthermore, deguelin exhibits inhibitory effects on paclitaxel resistance in HeyA8-MDR ovarian cancer cells, suggesting a potential mechanism for paclitaxel resensitization that may not be cell-specific. These findings suggest that deguelin holds promise as an anticancer therapeutic agent for overcoming chemoresistance in ovarian cancer.
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To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50 years or older. Intravitreal injection of SCD411 or aflibercept (2.0 mg) were administered every 4 weeks for the first three injections and every 8 weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of ± 3.0 letters. Patients were randomly assigned to receive either SCD411 (n = 288) or reference aflibercept (n = 288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411-aflibercept) was - 0.4 letters (90% confidence interval = - 1.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.
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Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Acuidade Visual , Humanos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Masculino , Feminino , Idoso , Acuidade Visual/efeitos dos fármacos , Resultado do Tratamento , Degeneração Macular/tratamento farmacológico , Pessoa de Meia-Idade , Método Duplo-Cego , Idoso de 80 Anos ou mais , Neovascularização de Coroide/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/administração & dosagemRESUMO
Background: TRF1, TRF2, and TERT (Telomerase reverse transcriptase) are telomere-associated factors that regulate telomere length. Genetic changes in these genes may be associated with cancer pathogenesis; however, this relationship has not yet been comprehensively elucidated in lung cancer. Aim: : Exploring the clinicopathologic and prognostic values of TRF1, TRF2, and TERT mRNA expression in non-small cell lung cancers (NSCLC). Methods: : The clinical significance of TRF1, TRF2, and TERT expression in 141 patients with NSCLC was investigated. Additionally, these findings were supported by the open big data from The Cancer Genome Atlas (TCGA). Results: : TRF1 and TRF2 expression levels tended to be associated with smoking, and TERT expression was positively correlated with age. The survival analysis showed that TRF1 expression predicted a better prognosis for squamous cell carcinoma (SCC), whereas TRF2 expression was associated with a shorter survival in adenocarcinoma. TCGA data also showed a better prognosis for SCC with TRF1 expression. However, the TRF2 results were not in agreement with our data. Conclusions: : We present the clinical and prognostic values of TRF1, TRF2, and TERT expression in NSCLC tissues and TCGA. Our findings suggest that TRF1 expression is a possible prognostic marker for NSCLC, particularly SCC.
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USP11 is overexpressed in colorectal cancer (CRC) and breast cancer tissues compared to normal tissues, suggesting a role in promoting cell proliferation and inhibiting cell death. In this study, we observed that depleting USP11 inhibits cell proliferation and delays cell cycle progression. This depletion leads to increased p53 protein levels due to an extended half-life, resulting in elevated p21 mRNA levels in a p53-dependent manner. The rise in p53 protein upon USP11 depletion is linked to a reduced half-life of MDM2, a known E3 ligase for p53, via enhanced polyubiquitination of MDM2. These findings indicate that USP11 might act as a deubiquitinase for MDM2, regulating the MDM2-p53-p21 axis. Additionally, USP11 depletion promotes the induction of senescent cells in a manner dependent on its deubiquitinase activity. Our findings provide insights into the physiological significance of high USP11 expression in primary tumors and its reduction in senescent cells, highlighting its potential as a therapeutic target.
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Senescência Celular , Inibidor de Quinase Dependente de Ciclina p21 , Mitose , Proteínas Proto-Oncogênicas c-mdm2 , Tioléster Hidrolases , Proteína Supressora de Tumor p53 , Ubiquitinação , Humanos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Tioléster Hidrolases/metabolismo , Tioléster Hidrolases/genética , Proliferação de Células , Linhagem Celular TumoralRESUMO
Introduction: Tuberculous pleural effusion (TPE) stands as one of the primary forms of extrapulmonary tuberculosis (TB) and frequently manifests in regions with a high prevalence of TB, consequently being a notable cause of pleural effusion in such areas. However, the differentiation between TPE and parapneumonic pleural effusion (PPE) presents diagnostic complexities. This study aimed to evaluate the potential of myeloid-derived suppressor cells (MDSCs) in the pleural fluid as a potential diagnostic marker for distinguishing between TPE and PPE. Methods: Adult patients, aged 18 years or older, who presented to the emergency room of a tertiary referral hospital and received a first-time diagnosis of pleural effusion, were prospectively enrolled in the study. Various immune cell populations, including T cells, B cells, natural killer (NK) cells, and MDSCs, were analyzed in both pleural fluid and peripheral blood samples. Results: In pleural fluid, the frequency of lymphocytes, including T, B, and NK cells, was notably higher in TPE compared to PPE. Conversely, the frequency of polymorphonuclear (PMN)-MDSCs was significantly higher in PPE. Notably, compared to traditional markers such as the neutrophil-to-lymphocyte ratio and adenosine deaminase level, the frequency of PMN-MDSCs emerged as a more effective discriminator between PPE and TPE. PMN-MDSCs demonstrated superior positive and negative predictive values and exhibited a higher area under the curve in the receiver operating characteristic curve analysis. PMN-MDSCs in pleural effusion increased the levels of reactive oxygen species and suppressed the production of interferon-gamma from T cells following nonspecific stimulation. These findings suggest that MDSC-mediated immune suppression may contribute to the pathology of both TPE and PPE. Discussion: The frequency of PMN-MDSCs in pleural fluid is a clinically useful indicator for distinguishing between TPE and PPE.
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Biomarcadores , Células Supressoras Mieloides , Derrame Pleural , Tuberculose Pulmonar , Humanos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Masculino , Feminino , Derrame Pleural/imunologia , Derrame Pleural/diagnóstico , Pessoa de Meia-Idade , Diagnóstico Diferencial , Adulto , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/imunologia , Idoso , Pneumonia/diagnóstico , Pneumonia/imunologia , Estudos Prospectivos , Tuberculose Pleural/diagnóstico , Tuberculose Pleural/imunologiaRESUMO
Background and objectives: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is caused by multiple factors. To explore novel targets for HCC treatment, we comprehensively analyzed the expression of HomeoboxB13 (HOXB13) and its role in HCC. Materials and Methods: The clinical significance of HCC was investigated using open gene expression databases, such as TIMER, UALCAN, KM, OSlihc, and LinkedOmics, and immunohistochemistry analysis. We also analyzed cell invasion and migration in HCC cell lines transfected with HOXB13-siRNA and their association with MMP9, E2F1, and MEIS1. Results: HOXB13 expression was higher in fibrolamellar carcinoma than in other histological subtypes. Its expression was associated with lymph node metastasis, histological stage, and tumor grade. It was positively correlated with immune cell infiltration of B cells (R = 0.246), macrophages (R = 0.182), myeloid dendritic cells (R = 0.247), neutrophils (R = 0.117), and CD4+ T cells (R = 0.258) and negatively correlated with immune cell infiltration of CD8+ T cells (R = -0.107). A positive correlation was observed between HOXB13, MMP9 (R = 0.176), E2F1 (R = 0.241), and MEIS1 (R = 0.189) expression (p < 0.001). The expression level of HOXB13 was significantly downregulated in both HepG2 and PLC/PFR/5 cell lines transfected with HOXB13-siRNA compared to that in cells transfected with NC siRNA (p < 0.05). Additionally, HOXB13 significantly affected cell viability and wound healing. Conclusions: HOXB13 overexpression may lead to poor prognosis in patients with HCC. Additional in vivo studies are required to improve our understanding of the biological role and the exact mechanism of action of HOXB13 in HCC.
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Carcinoma Hepatocelular , Proteínas de Homeodomínio , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Masculino , Feminino , Linhagem Celular Tumoral , Pessoa de Meia-Idade , Imuno-Histoquímica , Regulação Neoplásica da Expressão GênicaRESUMO
Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.
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Ferro , Lipocalina-2 , Cirrose Hepática , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica , Proteína de Ligação a Elemento Regulador de Esterol 1 , Animais , Humanos , Masculino , Camundongos , Tetracloreto de Carbono/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Ferro/metabolismo , Lipocalina-2/metabolismo , Lipocalina-2/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/genética , Cirrose Hepática/induzido quimicamente , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of ß-Catenin. Since several anagen-inductive genes are regulated by ß-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated ß-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3ß/ß-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H2O2)-induced HDPCs. The senescence-associated ß-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H2O2-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.
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Glicogênio Sintase Quinase 3 beta , Peróxido de Hidrogênio , Estresse Oxidativo , Floroglucinol , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , beta Catenina , Humanos , Floroglucinol/farmacologia , Floroglucinol/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Fosforilação/efeitos dos fármacos , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Folículo Piloso/citologia , Derme/citologia , Derme/metabolismo , Derme/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Alopecia/tratamento farmacológico , Alopecia/metabolismoRESUMO
Background: To evaluate the degree of deformation in patients with ankle osteoarthritis (OA), it is essential to measure the three-dimensional (3D), in other words, stereoscopic alignment of the ankle, subtalar, and foot arches. Generally, measurement of radiological parameters use two-dimensional (2D) anteroposterior and lateral radiographs in a weight-bearing state; however, computer-aided 3D analysis (Disior) using weight-bearing cone-beam computed tomography (CBCT) has recently been introduced. Methods: In this study, we compared the 2D human radiographic method with a stereoscopic image in patients with ankle arthritis. We enrolled 57 patients diagnosed with OA (28 left and 29 right) and obtained both standing radiographs and weight-bearing CBCT. Patients were divided by the Takakura stage. The interclass correlation coefficient (ICC) for each result was confirmed. Results: On the ICC between 2D radiographs and 3D analysis, the tibiotalar surface angle and lateral talo-1st metatarsal angle showed a good ICC grade (> 0.6), while other parameters did not have significant ICC results. Three-dimension was superior to radiographs in terms of statistical significance. Conclusions: We demonstrated that 2D and stereoscopic images are useful for the diagnosis of OA. Our study also confirmed that the radiographic features affected by ankle OA varied. However, according to the results, the typical radiography is not sufficient to diagnose and determine a treatment plan for ankle OA. Therefore, the method of using 3D images should be considered.
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Tornozelo , Osteoartrite , Humanos , Radiografia , Articulação do Tornozelo/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Suporte de Carga , Computadores , Reprodutibilidade dos TestesRESUMO
Paclitaxel is still used as a standard first-line treatment for ovarian cancer. Although paclitaxel is effective for many types of cancer, the emergence of chemoresistant cells represents a major challenge in chemotherapy. Our study aimed to analyze the cellular mechanism of dacomitinib, a pan-epidermal growth factor receptor (EGFR) inhibitor, which resensitized paclitaxel and induced cell cytotoxicity in paclitaxel-resistant ovarian cancer SKOV3-TR cells. We investigated the significant reduction in cell viability cotreated with dacomitinib and paclitaxel by WST-1 assay and flow cytometry analysis. Dacomitinib inhibited EGFR family proteins, including EGFR and HER2, as well as its downstream signaling proteins, including AKT, STAT3, ERK, and p38. In addition, dacomitinib inhibited the phosphorylation of Bad, and combination treatment with paclitaxel effectively suppressed the expression of Mcl-1. A 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay revealed a substantial elevation in cellular reactive oxygen species (ROS) levels in SKOV3-TR cells cotreated with dacomitinib and paclitaxel, which subsequently mediated cell cytotoxicity. Additionally, we confirmed that dacomitinib inhibits chemoresistance in paclitaxel-resistant ovarian cancer HeyA8-MDR cells. Collectively, our research indicated that dacomitinib effectively resensitized paclitaxel in SKOV3-TR cells by inhibiting EGFR signaling and elevating intracellular ROS levels.
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Fluoresceínas , Neoplasias Ovarianas , Paclitaxel , Quinazolinonas , Feminino , Humanos , Paclitaxel/farmacologia , Espécies Reativas de Oxigênio , Neoplasias Ovarianas/tratamento farmacológico , Apoptose , Receptores ErbBRESUMO
BACKGROUND: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis. METHODS: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality. RESULTS: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization. CONCLUSION: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization.
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Bronquiectasia , Haemophilus influenzae , Adulto , Humanos , Estudos Retrospectivos , Bronquiectasia/complicações , República da Coreia/epidemiologiaRESUMO
This study investigated natal factors influencing developmental defects of enamel (DDE) in premature infants using a newly refined preterm developmental defects of enamel (PDDE) index. Dental examinations were conducted on a cohort of 118 preterm infants (average age 3.5 ± 1.4 years) to record PDDE scores, while reviewing their medical records to examine natal factors. According to the logistic regression analysis, factors related to DDE prevalence were advanced maternal age, gestational age < 28 weeks, birth weight < 1000 g, 1 min APGAR score < 7, and hospitalization period > 2 months, which were significantly higher by 2.91, 5.53, 7.63, 10.02, and 4.0 times, respectively. According to regression analysis with generalized linear models, the PDDE scores were approximately 7.65, 4.96, and 15.0 points higher in premature children diagnosed with bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis, respectively. When endotracheal intubation was performed, the PDDE score was 5.06 points higher. The prevalence of PDDE was primarily observed bilaterally in the maxillary anterior teeth. Extremely preterm infants showed significantly delayed tooth eruption, suggesting that the influence of gestational age on dental development rates. Identifying the factors related to DDE in premature children can inform early dental interventions to support the oral health of high-risk children.
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Defeitos de Desenvolvimento do Esmalte Dentário , Nascimento Prematuro , Criança , Lactente , Feminino , Humanos , Recém-Nascido , Pré-Escolar , Estudos Prospectivos , Idade Gestacional , Lactente Extremamente PrematuroRESUMO
Ovarian cancer is the leading cause of death among gynecologic cancers. Paclitaxel is used as a standard first-line therapeutic agent for ovarian cancer. However, chemotherapeutic resistance and high recurrence rates are major obstacles to treating ovarian cancer. We have found that tephrosin, a natural rotenoid isoflavonoid, can resensitize paclitaxel-resistant ovarian cancer cells to paclitaxel. Cell viability, immunoblotting, and a flow cytometric analysis showed that a combination treatment made up of paclitaxel and tephrosin induced apoptotic death. Tephrosin inhibited the phosphorylation of AKT, STAT3, ERK, and p38 MAPK, all of which simultaneously play important roles in survival signaling pathways. Notably, tephrosin downregulated the phosphorylation of FGFR1 and its specific adapter protein FRS2, but it had no effect on the phosphorylation of the EGFR. Immunoblotting and a fluo-3 acetoxymethyl assay showed that tephrosin did not affect the expression or function of P-glycoprotein. Additionally, treatment with N-acetylcysteine did not restore cell cytotoxicity caused by a treatment combination made up of paclitaxel and tephrosin, showing that tephrosin did not affect the reactive oxygen species scavenging pathway. Interestingly, tephrosin reduced the expression of the anti-apoptotic factor XIAP. This study demonstrates that tephrosin is a potent antitumor agent that can be used in the treatment of paclitaxel-resistant ovarian cancer via the inhibition of the FGFR1 signaling pathway.
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Objectives: Since stroke is a serious health issue, novel therapeutic strategies are required. In a mouse model of ischemic stroke, this study analyzed the potential of electroacupuncture (EA) and tenuigenin (TE) to improve the efficacy of human mesenchymal stem cell (hMSC) transplantation. Methods: Middle cerebral artery occlusion (MCAO) with reperfusion was used to generate ischemic stroke. Forty-eight male C57BL/6 mice were randomly divided into five groups control, MCAO-operated, MCAO-EA, MCAO-TE, or MCAO + EA + TE. Subsequently, hMSCs were transplanted into the ischemic region and EA, TE, or the combination was administered. Behavior assessments and immunohistochemistry were conducted to evaluate motor and cognitive recovery and hMSCs survival, migration, and differentiation. Results: The combined treatment of EA and TE exhibited enhanced hMSCs survival, migration and differentiation into neural cell lineages while suppressing astrocyte formation. Immunohistochemistry demonstrated increased neurogenesis through hMSCs transplantation in the ischemic brain. Immediate behavioral improvements were not significantly different between groups, but there was a gradual recovery in motor and cognitive function over time. Conclusion: These findings highlight the potential of EA and TE co-treatment as a therapeutic strategy for ischemic stroke, opening avenues for further research to optimize treatment protocols and elucidate underlying mechanisms.
RESUMO
SUMMARY: Anatomic variation of the biceps brachii muscle (BBM) is frequently observed; its pattern is diverse and clinically important. During the educational dissection of a 78-year-old Korean male cadaver, six additional asymmetrical heads of the biceps brachii muscle (BBM) were found on both sides. On the right side, two additional heads originated from the humerus; the musculocutaneous nerve passed between these heads and the short head of the BBM. Four additional heads were found on the left side, anterior to the BBM, one of which originated from the pectoralis major muscle. Posterior to the BBM, two heads of tendons originated from the coracobrachialis muscle and one head of the muscle belly originated from the humerus. The left musculocutaneous nerve pierced the coracobrachialis muscle and continued distally passing between the short head of the BBM and the additional heads located posterior to the BBM. It then gave off the variant musculocutaneous nerve to the median nerve. On both sides, the short and long heads of the BBM had normal origins, insertions, and courses. This novel variation has various clinical and embryological implications.
RESUMEN: Con frecuencia se observa una variación anatómica del músculo bíceps braquial (MBB); su patrón es diverso y clínicamente importante. Durante la disección de un cadáver masculino coreano de 78 años, se encontraron seis cabezas asimétricas adicionales del músculo bíceps braquial en ambos lados. En el lado derecho, dos cabezas adicionales se originaban en el húmero; el nervio musculocutáneo atravesaba entre estas cabezas y la cabeza corta del MBB. Se encontraron cuatro cabezas adicionales en el lado izquierdo, anterior al MBB, una de las cuales se originaba en el músculo pectoral mayor. Posterior al MBB, dos cabezas tendinosas se originaban en el músculo coracobraquial y una cabeza de vientre muscular se originaba en el húmero. El nervio musculocutáneo izquierdo perforaba el músculo coracobraquial y continuaba distalmente pasando entre la cabeza corta del MBB y las cabezas adicionales ubicadas por detrás del MBB. Luego emitía la variante el nervio musculocutáneo al nervio mediano. En ambos lados, las cabezas corta y larga del MBB tenían orígenes, inserciones y trayectos normales. Esta nueva variación tiene varias implicaciones clínicas y embriológicas.
Assuntos
Humanos , Masculino , Idoso , Músculo Esquelético/inervação , Variação Anatômica , Nervo Musculocutâneo/anatomia & histologia , CadáverRESUMO
SUMMARY: COVID-19 has forced anatomists to perform non-face-to-face education using lecture videos. A Korean anatomist has given (white and black) board lectures and distributed lecture videos to the public for many years. This study was to verify the effects of open board lecture videos in the anatomy field. A questionnaire survey was carried out with the help of medical students who were exposed to the board lecture videos. The video provider uploaded the lecture videos on YouTube, where the viewing numbers were counted. At a medical school where the video provider belonged, the students mainly watched the lecture videos before the anatomy class. The watching hours of the lecture videos were related to the written examination scores. Students gave positive and negative comments on the board lectures. At the other two medical schools, students partly watched the lecture videos regardless of the teacher who delivered the lectures. The results suggested that students understood the board lectures themselves. On YouTube, the lecture videos were viewed by approximately 1,000 students. This paper introduces the desirable aspects of open board lecture videos on anatomy. The videos could enhance the quality of both students and teacher.
RESUMEN: COVID-19 ha obligado a los anatomistas a realizar una enseñanza no presencial mediante videos de conferencias. Un anatomista coreano ha impartido conferencias (en blanco y negro) y ha distribuido videos de conferencias al público durante muchos años. El objetivo de este estudio fue verificar los efectos de los videos de conferencias de pizarra abierta en el campo de la anatomía. Se llevó a cabo una encuesta con la ayuda de estudiantes de medicina que habían sido expuestos a los videos de conferencias de la pizarra. El proveedor de videos subió los videos de las conferencias a YouTube, donde se contabilizó el número de visualizaciones. En una facultad de medicina a la que pertenecía el proveedor de videos, los estudiantes vieron principalmente los videos de conferencias antes de la clase de anatomía. Las horas de revisión de los vídeos de las conferencias se relacionaron con las puntuaciones de los exámenes escritos. Los estudiantes dieron comentarios positivos y negativos sobre las conferencias de la pizarra. En las otras dos facultades de medicina, los estudiantes vieron parcialmente los videos de las clases, independientemente del profesor que las impartiera. Los resultados sugerían que los estudiantes entendieron las conferencias de la pizarra por sí mismos. En YouTube, los videos de las conferencias fueron vistos por aproximadamente 1000 estudiantes. Este artículo presenta los aspectos deseables de los videos de conferencias abiertas sobre anatomía. Los videos podrían mejorar la calidad tanto de los estudiantes como del profesor.
Assuntos
Humanos , Estudantes de Medicina , Gravação em Vídeo , Educação a Distância , Anatomia Regional/educação , Inquéritos e Questionários , Educação de Graduação em Medicina , República da CoreiaRESUMO
SUMMARY: The variations in the serratus anterior (SA) muscle are common. Here, we report a rare variation of the muscle origin with a potentially great clinical implication. We found an aberrant SA variation in an 81-year-old Korean male cadaver during a routine dissection for medical students. Additional slip (AS) of the SA originated from the clavipectoral fascia and the pectoralis minor. It traveled inferiorly and merged to the typical SA part. Precise knowledge about SA variations is clinically valuable; therefore, clinicians should be aware of the possible variation.
RESUMEN: Las variaciones en el músculo serrato anterior (MSA) son comunes. En este trabajo informamos una variación rara del origen muscular con una implicación clínica potencialmente importante. Encontramos una variación aberrante del MSA en un cadáver masculino, coreano de 81 años, durante una disección de rutina para estudiantes de medicina, con un fascículo adicional del MSA originado en la fascia clavipectoral y el músculo pectoral menor. Este fascículo se dirigió inferiormente y se fu- sionó con la parte común de MSA. El conocimiento preciso sobre las variaciones de MSA es útil clínicamente; por lo tanto, los médicos deben ser conscientes de esta posible variación.
Assuntos
Humanos , Masculino , Idoso de 80 Anos ou mais , Músculo Esquelético/anatomia & histologia , Variação Anatômica , Cadáver , FásciaRESUMO
The axillary arch is a variant slip extending between the latissimus dorsi muscle and the pectoralis major. During educational dissection, a variant muscle was found in left arm of 70-year-old female cadaver. A slip muscle originated from the lateral margin of the latissimus dorsi and crossed the axilla obliquely. Therefore, we defined this muscular variation as axillary arch. It ran anterior (superficial) to the medial and lateral cords of the brachial plexus, and then it inserted to coracoid process. We reported this variant muscle and discussed its clinical significances.
El arco axilar es una variante que se extiende entre el músculo dorsal ancho y el pectoral mayor. Durante la disección educativa, se encontró una variante muscular en el brazo izquierdo de un cadáver de una mujer de 70 años. El músculo deslizante se originó en el borde lateral del dorsal ancho y cruzó la axila oblicuamente. Por lo tanto, definimos esta variación muscular como el arco axilar. Se extendió anterior (superficial) a los cordones medial y lateral del plexo braquial, y luego se insertó en el proceso coracoideo. Reportamos esta variante muscular y discutimos sus significados clínicas.