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OBJECTIVE: Advances in mobile technology are helping with health management practices, and smart toothbrushes provide proper dental care by collecting and analyzing users' toothbrushing data. The purpose of this study is to assess the effect of a telemonitoring device on oral hygiene management in individuals with intellectual or developmental disabilities and its role in promoting oral health. MATERIALS AND METHODS: Participants were split into two groups: one initially using the telemonitoring device (telemonitoring device/manual toothbrush) and the other using it later (manual toothbrush/telemonitoring device), with a one-month washout period. The study compared plaque index, halitosis, changes in oral microbiota, and guardian questionnaire responses between the groups. RESULTS: In period 1, the QHI index score significantly decreased from 1.93 to 0.83 in the group using the remote monitoring device, compared to an increase from 1.75 to 2.01 in the manual toothbrush group. Additionally, toothbrushing frequency, time, and cooperation increased by 0.82 ± 0.60, 0.82 ± 1.16, and 1.09 ± 0.94, respectively, with initial telemonitoring device use. However, these measures decreased by -1.45 ± 0.68, -1.09 ± 0.70, and - 1.00 ± 1.00 after switching to a manual toothbrush, and decreased by -0.64 ± 0.67, -0.27 ± 1.19, and 0.09 ± 0.94 overall, respectively. However, there were no significant differences in oral microbiota between the groups at these different time points. CONCLUSIONS: The study shows that telemonitoring devices effectively reduce plaque index and improve toothbrushing frequency, time, and cooperation. However, these benefits decrease after switching to a manual toothbrush. Follow-up is needed to assess satisfaction and compliance with telemonitoring device use. CLINICAL RELEVANCE: Using telemonitoring devices in the oral health management of individuals with intellectual and developmental disabilities can improve their oral health quality.
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Estudos Cross-Over , Deficiência Intelectual , Higiene Bucal , Cooperação do Paciente , Escovação Dentária , Humanos , Feminino , Masculino , Escovação Dentária/instrumentação , Higiene Bucal/instrumentação , Adulto , Inquéritos e Questionários , Deficiências do Desenvolvimento , Índice de Placa Dentária , Telemedicina/instrumentação , Pessoa de Meia-Idade , Halitose/terapiaRESUMO
In critical care settings, ultrasound (US) of the quadriceps muscle and Bioelectrical Impedance Analysis (BIA) are noninvasive and widely available tools to evaluate muscle mass. We studied whether baseline muscle mass affects physical function in intensive care unit (ICU) survivors after discharge. This retrospective review of a prospective cohort enrolled 30 patients admitted to the medical ICU between April 2016 and June 2018. On ICU admission, quadriceps muscle thickness and skeletal muscle mass were measured using US and BIA, respectively. Muscle strength and physical function were measured using handgrip dynamometry, the 6-min walk test, and the Barthel index questionnaire survey during every clinic visit at 1, 3, 6, and 12 months after hospital discharge. Skeletal muscle mass at ICU admission was statistically correlated with the 6-min walk distance (6MWD) and Barthel index score. The segmental lean mass of the right arm was also positively correlated with handgrip muscle strength at 6 months after discharge. Likewise, the correlation between quadriceps muscle thickness at ICU admission and 6MWD at 6 months after discharge was positive and statistically significant. Multivariate regression analysis showed that skeletal muscle mass was associated with a reduced 6MWD, but the length of ICU stay was not. The segmental lean mass of the right arm also showed a significant association with handgrip strength after discharge. Low muscle mass on ICU admission is associated with reduced muscle strength, causing impaired physical function after hospital discharge in ICU survivors.
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Unidades de Terapia Intensiva , Músculo Quadríceps , Sobreviventes , Humanos , Masculino , Feminino , Estudos Retrospectivos , Unidades de Terapia Intensiva/estatística & dados numéricos , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Idoso , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/fisiopatologia , Sobreviventes/estatística & dados numéricos , Força Muscular/fisiologia , Força da Mão/fisiologia , Impedância Elétrica , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , UltrassonografiaRESUMO
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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Abscission is the shedding of plant organs in response to developmental and environmental cues. Abscission involves cell separation between two neighboring cell types, residuum cells (RECs) and secession cells (SECs) in the floral abscission zone (AZ) in Arabidopsis thaliana. However, the regulatory mechanisms behind the spatial determination that governs cell separation are largely unknown. The class I KNOTTED-like homeobox (KNOX) transcription factor BREVIPEDICELLUS (BP) negatively regulates AZ cell size and number in Arabidopsis. To identify new players participating in abscission, we performed a genetic screen by activation tagging a weak complementation line of bp-3. We identified the mutant ebp1 (enhancer of BP1) displaying delayed floral organ abscission. The ebp1 mutant showed a concaved surface in SECs and abnormally stacked cells on the top of RECs, in contrast to the precisely separated surface in the wild-type. Molecular and histological analyses revealed that the transcriptional programming during cell differentiation in the AZ is compromised in ebp1. The SECs of ebp1 have acquired REC-like properties, including cuticle formation and superoxide production. We show that SEPARATION AFFECTING RNA-BINDING PROTEIN1 (SARP1) is upregulated in ebp1 and plays a role in the establishment of the cell separation layer during floral organ abscission in Arabidopsis.
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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
Objectives: Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of Polygonum multiflorum on cognitive function. Methods: This study focused primarily on the effects of Polygonum multiflorum and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer's disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind Polygonum multiflorum's impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at Polygonum multiflorum's effects on cognitive decline and AD. Results: According to recent research, Poligonum multiflorum and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis. Conclusion: This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of Polygonum multiflorum. We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders.
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Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management.
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Inteligência Artificial , Escarro , Tuberculose Pulmonar , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Resultado do Tratamento , Idoso , Escarro/microbiologia , Adulto , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , República da Coreia , Tomografia Computadorizada por Raios X/métodos , Antituberculosos/uso terapêutico , Radiografia Torácica/métodosRESUMO
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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During the last decade, the generation and accumulation of petabase-scale high-throughput sequencing data have resulted in great challenges, including access to human data, as well as transfer, storage, and sharing of enormous amounts of data. To promote data-driven biological research, the Korean government announced that all biological data generated from government-funded research projects should be deposited at the Korea BioData Station (K-BDS), which consists of multiple databases for individual data types. Here, we introduce the Korean Nucleotide Archive (KoNA), a repository of nucleotide sequence data. As of July 2022, the Korean Read Archive in KoNA has collected over 477 TB of raw next-generation sequencing data from national genome projects. To ensure data quality and prepare for international alignment, a standard operating procedure was adopted, which is similar to that of the International Nucleotide Sequence Database Collaboration. The standard operating procedure includes quality control processes for submitted data and metadata using an automated pipeline, followed by manual examination. To ensure fast and stable data transfer, a high-speed transmission system called GBox is used in KoNA. Furthermore, the data uploaded to or downloaded from KoNA through GBox can be readily processed using a cloud computing service called Bio-Express. This seamless coupling of KoNA, GBox, and Bio-Express enhances the data experience, including submission, access, and analysis of raw nucleotide sequences. KoNA not only satisfies the unmet needs for a national sequence repository in Korea but also provides datasets to researchers globally and contributes to advances in genomics. The KoNA is available at https://www.kobic.re.kr/kona/.
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Bases de Dados de Ácidos Nucleicos , República da Coreia , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodosRESUMO
Wastewater treatment plants (WWTPs) are considered a significant microplastic discharge source. To evaluate the amount and characteristics of microplastics discharged from WWTPs in South Korea, we selected 22 municipal WWTPs nationally and investigated microplastics at each treatment stage. The mean microplastic removal efficiency by WWTPs was >99%, and most of the microplastics were removed by sedimentation with the second clarifier during wastewater treatment. Consequently, the microplastic removal efficiency of WWTPs did not significantly differ from that of the adopted wastewater treatment technology because a second clarifier was applied in most WWTPs. However, for WWTPs operating a tertiary treatment process, the removal efficiency was enhanced compared with that of WWTPs discharging after a second clarifier. Although the microplastic removal efficiency was high by WWTP, the discharge contribution to the water environment could not be ignored because of the amount of treated wastewater, resulting in an increase of 5.8-270.9 items/m3 of microplastics in the receiving water. The characteristics of microplastics in WWTPs, including their components, shape, and size, were also evaluated. The most detected components included polytetrafluoroethylene and polyester. Most microplastics detected were categorized as fragments and fibers, while other types were hardly detected. The size of more than 70% of the microplastics detected in WWTPs was under 300 µm, implying that the size of microplastics required to control in WWTPs was much smaller than the defined size of microplastics. An evaluation of the correlation between other pollution factors and microplastic abundance did not reveal positive correlations, and microplastic occurrence was not affected by changing seasons, which may need to be evaluated with further studies. Research should also be performed on the effect of influent sources on the level of microplastic abundance and fate of ultrafine plastics in WWTPs.
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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
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
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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Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.
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Betaína-Homocisteína S-Metiltransferase , Hepatócitos , Fígado , Metionina , Camundongos Knockout , Espécies Reativas de Oxigênio , Receptores Citoplasmáticos e Nucleares , Triglicerídeos , Animais , Fígado/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Betaína-Homocisteína S-Metiltransferase/metabolismo , Betaína-Homocisteína S-Metiltransferase/genética , Hepatócitos/metabolismo , Metionina/metabolismo , Triglicerídeos/metabolismo , Regiões Promotoras Genéticas/genética , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Peroxidação de LipídeosRESUMO
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
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
OBJECTIVES: The need for interoperability at the national level was highlighted in Korea, leading to a consensus on the importance of establishing national standards that align with international technological standards and reflect contemporary needs. This article aims to share insights into the background of the recent national health data standardization policy, the activities of the Health Data Standardization Taskforce, and the future direction of health data standardization in Korea. METHODS: To ensure health data interoperability, the Health Data Standardization Taskforce was jointly organized by the public and private sectors in December 2022. The taskforce operated three working groups. It reviewed international trends in interoperability standardization, assessed the current status of health data standardization, discussed its vision, mission, and strategies, engaged in short-term standardization activities, and established a governance system for standardization. RESULTS: On September 15, 2023, the notice of "Health Data Terminology and Transmission Standards" in Korea was thoroughly revised to improve the exchange of health information between information systems and ensure interoperability. This notice includes the Korea Core Data for Interoperability (KR CDI) and the Korea Core Data Transmission Standard (HL7 FHIR KR Core), which are outcomes of the taskforce's efforts. Additionally, to reinforce the standardized governance system, the Health-Data Standardization Promotion Committee was established. CONCLUSIONS: Active interest and support from medical informatics experts are needed for the development and widespread adoption of health data standards in Korea.
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OBJECTIVES: Education in biomedical and health informatics is essential for managing complex healthcare systems, bridging the gap between healthcare and information technology, and adapting to the digital requirements of the healthcare industry. This review presents the current status of biomedical and health informatics education domestically and internationally and proposes recommendations for future development. METHODS: We analyzed evidence from reports and papers to explore global trends and international and domestic examples of education. The challenges and future strategies in Korea were also discussed based on the experts' opinions. RESULTS: This review presents international recommendations for establishing education in biomedical and health informatics, as well as global examples at the undergraduate and graduate levels in medical and nursing education. It provides a thorough examination of the best practices, strategies, and competencies in informatics education. The review also assesses the current state of medical informatics and nursing informatics education in Korea. We highlight the challenges faced by academic institutions and conclude with a call to action for educators to enhance the preparation of professionals to effectively utilize technology in any healthcare setting. CONCLUSIONS: To adapt to the digitalization of healthcare, systematic and continuous workforce development is essential. Future education should prioritize curriculum innovations and the establishment of integrated education programs, focusing not only on students but also on educators and all healthcare personnel in the field. Addressing these challenges requires collaboration among educational institutions, academic societies, government agencies, and international bodies dedicated to systematic and continuous workforce development.
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BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.
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Antibacterianos , Infecções por Mycobacterium não Tuberculosas , Qualidade de Vida , Humanos , Masculino , Feminino , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , República da Coreia , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Micobactérias não Tuberculosas/efeitos dos fármacos , Resultado do TratamentoRESUMO
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.