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The regenerative ability of planarians relies on their adult pluripotent stem cell population. Although all stem cells express a piwi homolog, recently it has become possible to classify the piwi+ stem cell population into specialized subpopulations according to the expression of genes related to differentiation. However, piwi+ stem cells behave practically as a homogeneous population after amputation, during which stem cells show accelerated proliferation, named 'induced hyperproliferation'. Here, we show that plac8-A was expressed in almost all of the stem cells, and that a decrease of the plac8-A expression level led to induced hyperproliferation uniformly in a broad stem cell subpopulation after amputation. This reduction of plac8-A expression was caused by activated JNK signaling after amputation. Pharmacological inhibition of JNK signaling caused failure to induce hyperproliferation and resulted in regenerative defects. Such defects were abrogated by simultaneous knockdown of plac8-A expression. Thus, JNK-dependent suppression of plac8-A expression is indispensable for stem cell dynamics involved in regeneration. These findings suggest that plac8-A acts as a molecular switch of piwi+ stem cells for entry into the regenerative state after amputation.
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Proteínas del Helminto/genética , Planarias/fisiología , Regeneración/fisiología , Animales , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proliferación Celular , Regulación hacia Abajo , Proteínas del Helminto/antagonistas & inhibidores , Proteínas del Helminto/metabolismo , Sistema de Señalización de MAP Quinasas , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , Interferencia de ARN , ARN Bicatenario/metabolismoRESUMEN
Over the past decade, there has been a significant rise in the use of vaping devices, particularly among adolescents, raising concerns for effects on respiratory health. Pressingly, many recent vaping-related lung injuries are unexplained by current knowledge, and the overall implications of vaping for respiratory health are poorly understood. This study investigates the effect of hydrophobic vaping liquid chemicals on the pulmonary surfactant biophysical function. We focus on the commonly used flavoring benzaldehyde and its vaping byproduct, benzaldehyde propylene glycol acetal. The study involves rigorous testing of the surfactant biophysical function in Langmuir trough and constrained sessile drop surfactometer experiments with both protein-free synthetic surfactant and hydrophobic protein-containing clinical surfactant models. The study reveals that exposure to these vaping chemicals significantly interferes with the synthetic and clinical surfactant biophysical function. Further atomistic simulations reveal preferential interactions with SP-B and SP-C surfactant proteins. Additionally, data show surfactant lipid-vaping chemical interactions and suggest significant transfer of vaping chemicals to the experimental subphase, indicating a toxicological mechanism for the alveolar epithelium. Our study, therefore, reveals novel mechanisms for the inhalational toxicity of vaping. This highlights the need to reassess the safety of vaping liquids for respiratory health, particularly the use of aldehyde chemicals as vaping flavorings.
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Sistemas Electrónicos de Liberación de Nicotina , Surfactantes Pulmonares , Vapeo , Adolescente , Humanos , Aldehídos , Benzaldehídos , Tensoactivos , AromatizantesRESUMEN
BACKGROUND: In South Korea, Korean Chinese workers experience ethnic discrimination although they share physical similarities and ethnic heritage with native-born Koreans. This study aimed to examine whether perceived ethnic discrimination is associated with poor self-rated health and whether the association differs by gender among Korean Chinese waged workers in South Korea. METHODS: We conducted a pooled cross-sectional analysis using data of 13,443 Korean Chinese waged workers from the Survey on Immigrants' Living Conditions and Labor Force conducted in 2018, 2020, and 2022. Based on perceived ethnic discrimination, asking for fair treatment, and subsequent situational improvement, respondents were classified into the following four groups: "Not experienced," "Experienced, not asked for fair treatment," "Experienced, asked for fair treatment, not improved," and "Experienced, asked for fair treatment, improved." Poor self-rated health was assessed using a single question "How is your current overall health?" We applied logistic regression to examine the association between perceived ethnic discrimination and poor self-rated health, with gender-stratified analyses. RESULTS: We found an association between ethnic discrimination and poor self-rated health among Korean Chinese waged workers. In the gender-stratified analysis, the "Experienced, not asked for fair treatment" group was more likely to report poor self-rated health compared to the "Not experienced" group, regardless of gender. However, gender differences were observed in the group stratified by situational improvements. For male workers, no statistically significant association was found in the "Experienced, asked for fair treatment, improved" group with poor self-rated health (odd ratios: 0.87, 95% confidence intervals: 0.30-2.53). Conversely, among female workers, a statistically significant association was observed (odd ratios: 2.63, 95% confidence intervals: 1.29-5.38). CONCLUSIONS: This study is the first to find an association between perceived ethnic discrimination and poor self-rated health, along with gender differences in the association between situational improvements after asking for fair treatment and poor self-rated health among Korean Chinese waged workers in South Korea.
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Autoevaluación Diagnóstica , Estado de Salud , Discriminación Percibida , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , China/etnología , Estudios Transversales , Pueblos del Este de Asia , Racismo , República de Corea , Factores Sexuales , Encuestas y CuestionariosRESUMEN
BACKGROUND: Prophylactic antibiotics (PAs) are standard for preventing surgical site infections (SSIs) post-colorectal surgery. This study aims to compare the effect of additional empiric oral antibiotics (OAs) alongside routine PAs to identify SSI risk factors. METHODS: A retrospective observatory analysis was conducted from January 2019 to December 2022 at Asan Medical Center, Seoul, Korea. The cohort was divided into two groups: PA given 1 h before surgery and discontinued within 24 h, and OA administered empiric OAs during mechanical bowel preparation in addition to PA. RESULTS: From a total of 6736 patients, 3482 were in the PA group and 3254 in the OA group. SSI incidence showed no significant intergroup difference (p = 0.374) even after propensity score matching (p = 0.338). The multivariable analysis revealed male sex [odds ratio (OR): 2.153, 95% confidence interval (CI): 1.626-2.852, and p = 0.001], open surgery (OR: 3.335, 95% CI: 2.456-4.528, and p = 0.001), dirty wound (OR: 2.171, 95% CI: 1.256-3.754, and p = 0.006), and an operation time of more than 145 min (OR: 2.110, 95% CI: 1.324-3.365, and p = 0.002) as SSI risk factors. In rectal surgery subgroup, OA demonstrated a protective effect against SSI (OR: 0.613, 95% CI: 0.408-0.922, and p = 0.019) and in laparoscopic approach (OR: 0.626, 95% CI: 0.412-0.952, and p = 0.028). CONCLUSIONS: OA did not affect SSI incidence in colorectal surgeries. Male sex, open surgery, dirty wounds, and longer operation time were risk factors for SSI. However, for rectal and laparoscopic surgery, OA was a protective factor for SSI.
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Antibacterianos , Profilaxis Antibiótica , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/epidemiología , Masculino , Femenino , Profilaxis Antibiótica/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Administración Oral , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Anciano , Factores de Riesgo , Catárticos/administración & dosificación , Catárticos/uso terapéutico , Cuidados Preoperatorios/métodos , Incidencia , Adulto , Cirugía Colorrectal/efectos adversos , República de Corea/epidemiologíaRESUMEN
OBJECTIVE: To examine the association between adult children's migration and depression among older parents in Central and Eastern Europe (CEE) and explore the role of intergenerational support in contributing to their depression. METHODS: Data are from the eighth wave of the Survey of Health, Ageing and Retirement in Europe (SHARE), pooling a study sample of 11 CEE countries, with a cross-sectional design. Analysis of covariance (ANCOVA) and hierarchical linear regression were conducted using a study sample of 9133 respondents. RESULTS: Older adults whose children migrated over 500 km were more likely to experience depression compared to those with no migrant child or all children within 500 km. Among intergenerational support, frequent parent-child contact mitigated the effects of migration on depression in older parents with all their children who migrated over 500 km. CONCLUSION: This study suggests that older parents with migrant children over 500 km away should be considered a vulnerable population at risk for mental health in CEE countries. It is crucial for local governments and policymakers to address these challenges through improving integrated mental health and social programs for better mental health outcomes among older adults in CEE countries.
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Hijos Adultos , Salud Mental , Humanos , Anciano , Hijos Adultos/psicología , Estudios Transversales , Europa (Continente)/epidemiología , Europa Oriental/epidemiología , Padres/psicologíaRESUMEN
Magnesium (Mg) has many unique properties suitable for applications in the fields of energy conversion and storage. These fields presently rely on noble metals for efficient performance. However, among other challenges, noble metals have low natural abundance, which undermines their sustainability. Mg has a high negative standard reduction potential and a unique crystal structure, and its low melting point at 650 °C makes it a good candidate to replace or supplement numerous other metals in various energy applications. These attractive features are particularly helpful for improving the properties and limits of materials in energy systems. However, knowledge of Mg and its practical uses is still limited, despite recent studies which have reported Mg's key roles in synthesizing new structures and modifying the chemical properties of materials. At present, information about Mg chemistry has been rather scattered without any organized report. The present review highlights the chemistry of Mg and its uses in energy applications such as electrocatalysis, photocatalysis, and secondary batteries, among others. Future perspectives on the development of Mg-based materials are further discussed to identify the challenges that need to be addressed.
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Background and Objectives: The analgesia/nociception index (ANI) potentially monitors nociceptive status during anesthesia, but its link to preoperative pain sensitivity is unclear. We investigated the relationship between pre-anesthetic ANI scores and propofol injection pain (PIP) in patients receiving remifentanil. Materials and Methods: This study included 124 male patients aged 19-60 undergoing general anesthesia (ASA class I or II). Patients were randomized to group R (n = 62, remifentanil 4 ng/mL) or group C (n = 62, saline). The primary outcome was the association between PIP and ANI. Secondary outcomes included the incidence and severity of PIP or rocuronium-induced withdrawal movement (RIWM) and their association with ANI. Results: PIP and RIWM incidence and severity were lower in group R than in group C. A weak negative correlation between PIP and ANI at pre-induction (rpb = -0.21, p = 0.02, rpb = -0.37, p < 0.01) and a moderate negative correlation during propofol injection (rpb = -0.48, p = 0.02) were observed. A significant negative correlation was found between RIWM and ANI during rocuronium injection (τb = -0.61, p < 0.01). AUC, cut-off value, specificity, and sensitivity in ANI at pre-induction for predicting PIP were 0.67 (p = 0.02), 59, 76%, and 55%, respectively. AUC, cut-off value, specificity, and sensitivity in ANI during propofol injection for PIP were 0.77 (p < 0.01), 65, 81%, and 67%, respectively. Conclusions: ANI scores demonstrated significant differences between groups, suggesting potential predictive value for PIP despite the low pre-induction AUC value. This study highlights the potential of using ANI scores to predict and manage PIP in patients receiving remifentanil.
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Analgesia , Propofol , Humanos , Masculino , Propofol/efectos adversos , Remifentanilo/efectos adversos , Nocicepción , Anestésicos Intravenosos/efectos adversos , Estudios Prospectivos , Rocuronio , Frecuencia Cardíaca , Dolor , Anestesia GeneralRESUMEN
Background and Objectives: The effects of midazolam, a benzodiazepine, on pain perception are complex on both spinal and supraspinal levels. It is not yet known whether remimazolam clinically attenuates or worsens pain. The present study investigated the effect of intraoperative remimazolam on opioid-induced hyperalgesia (OIH) in patients undergoing general anesthesia. Materials and Methods: The patients were randomized into three groups: group RHR (6 mg/kg/h initial dose followed by 1 mg/kg/h remimazolam and 0.3 µg /kg/min remifentanil), group DHR (desflurane and 0.3 µg /kg/min remifentanil) or group DLR (desflurane and 0.05 µg/kg /min remifentanil). The primary outcome was a mechanical hyperalgesia threshold, while secondary outcomes included an area of hyperalgesia and clinically relevant pain outcomes. Results: Group RHR had a higher mechanical hyperalgesia threshold, a smaller hyperalgesia postoperative area at 24 h, a longer time to first rescue analgesia (p = 0.04), lower cumulative PCA volume containing morphine postoperatively consumed for 24 h (p < 0.01), and lower pain intensity for 12 h than group DHR (p < 0.001). However, there was no significant difference in OIH between groups RHR and DLR. Conclusions: Group RHR, which received remimazolam, attenuated OIH, including mechanically evoked pain and some clinically relevant pain outcomes caused by a high dose of remifentanil. Further research is essential to determine how clinically meaningful and important the small differences observed between the two groups are.
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Hiperalgesia , Laparoscopía , Humanos , Hiperalgesia/inducido químicamente , Analgésicos Opioides/efectos adversos , Remifentanilo , Desflurano , Estudios Prospectivos , Benzodiazepinas , Percepción del Dolor , DolorRESUMEN
Background and Objectives: The mechanisms involved in the development of brain metastasis (BM) remain elusive. Here, we investigated whether BM is associated with spine involvement in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: A consecutive 902 patients with metastatic NSCLC were included from the Inha Lung Cancer Cohort. Patients with BM at diagnosis or subsequent BM development were evaluated for both spine involvement in NSCLC and anatomic proximity of BM to the cerebrospinal fluid (CSF) space. Results: At diagnosis, BM was found in 238 patients (26.4%) and bone metastasis was found in 393 patients (43.6%). In patients with bone metastasis, spine involvement was present in 280 patients. BM subsequently developed in 82 (28.9%) of 284 patients without BM at diagnosis. The presence of spine metastasis was associated with BM at diagnosis and subsequent BM development (adjusted odd ratios and 95% confidence intervals = 2.42 and 1.74-3.37, p < 0.001; 1.94 and 1.19-3.18, p = 0.008, respectively). Most patients with spine metastasis, either with BM at diagnosis or subsequent BM, showed BM lesions located adjacent (within 5mm) to the CSF space (93.8% of BM at the diagnosis, 100% of subsequent BM). Conclusions: These findings suggest that the presence of spine involvement is a risk factor for BM development in NSCLC patients with bone metastasis.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Oportunidad Relativa , PacientesRESUMEN
The International Psychogeriatric Association (IPA) has expressed significant concerns over the use of physical restraints in older people across diverse aged care settings. Following an extensive analysis of the available literature, the IPA's Early Career Network (ECN) has formulated a collection of evidence-based recommendations aimed at guiding the use of physical restraints within various care contexts and demographic groups. Physical restraints not only infringe upon human rights but also raise significant safety concerns that adversely impact the physical, psychological, social, and functional well-being of older adults. Furthermore, their effectiveness in geriatric settings remains inadequate. Given these considerations, the IPA and its ECN firmly assert that the use of physical restraints should only be considered as a final recourse in the care of older people.
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The psychological impact of indirect trauma is unknown among North Korean (NK) refugees. We aimed to investigate the effects of direct and indirect trauma on the mental health of NK refugees in South Korea and evaluate the potential moderating effect of acculturative stress in this association. Using respondent-driven sampling, we recruited 323 NK refugees for this retrospective study. We measured exposure to direct and indirect trauma as independent variables, and posttraumatic stress symptoms (PTSS) and symptoms of depression and anxiety as dependent variables. After implementing multivariate imputation using chained equations, the associations between trauma type and psychological outcomes were assessed using ordinary least squares regression analyses, controlling for demographic covariates; the potential effect modification of acculturative stress was studied by adding an interaction term to the analyses. PTSS and symptoms of depression and anxiety were significantly associated with exposure to both direct, Bs = 0.24, 0.16, 0.19, respectively, p < .001s, and indirect trauma, Bs = 0.13, 0.08, 0.07, respectively, ps < .001. Although we did not observe significant effect modification, the magnitude of association between indirect trauma and PTSS significantly differed between the high, B = 0.18, p < .001, and low acculturative stress groups, B = 0.08, p = .024. These findings suggest that indirect trauma is associated with a more severe mental health consequence among NK refugees who experience high acculturative stress. Efforts to mitigate acculturative stress may reduce the mental health consequences of indirect trauma exposure.
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Refugiados , Trastornos por Estrés Postraumático , Humanos , Salud Mental , Trastornos por Estrés Postraumático/psicología , Refugiados/psicología , República Popular Democrática de Corea , Estudios Retrospectivos , República de CoreaRESUMEN
For a task-oriented dialogue system to provide appropriate answers to and services for users' questions, it is necessary for it to be able to utilize knowledge related to the topic of the conversation. Therefore, the system should be able to select the most appropriate knowledge snippet from the knowledge base, where external unstructured knowledge is used to respond to user requests that cannot be solved by the internal knowledge addressed by the database or application programming interface. Therefore, this paper constructs a three-step knowledge-grounded task-oriented dialogue system with knowledge-seeking-turn detection, knowledge selection, and knowledge-grounded generation. In particular, we propose a hierarchical structure of domain-classification, entity-extraction, and snippet-ranking tasks by subdividing the knowledge selection step. Each task is performed through the pre-trained language model with advanced techniques to finally determine the knowledge snippet to be used to generate a response. Furthermore, the domain and entity information obtained because of the previous task is used as knowledge to reduce the search range of candidates, thereby improving the performance and efficiency of knowledge selection and proving it through experiments.
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Comunicación , Lenguaje , Bases del Conocimiento , Procesamiento de Lenguaje Natural , Programas InformáticosRESUMEN
Background and objectives: Anesthesia maintenance agents affect the incidence of postoperative shivering (PS) after general anesthesia. This study compared the effects of remimazolam with sevoflurane on PS in patients undergoing laparoscopic gynecologic surgery under general anesthesia. Materials and methods: Seventy-four patients were allocated into one of two groups. In anesthesia maintenance, group S received sevoflurane and remifentanil, and group R received remimazolam and remifentanil. Results: The incidence and severity of postoperative shivering, mean arterial pressure (MAP), heart rate (HR), core body temperature, and the association of PS with hypothermia, MAP, or HR in the post-anesthesia care unit (PACU) were measured. Group R had significantly lower rates of perioperative hypothermia (58.8 vs. 27.8%, p = 0.009) and postoperative shivering (41.2 vs. 19.4%, p = 0.047). The severity of PS was also lower in group R than in group S (p = 0.034). Core body temperature was significantly higher in group R than in group S from 10 min after induction (p = 0.047) to the PACU (p = 0.009). MAP and HR were significantly higher in group R than in group S from 20 min after induction (p = 0.047) to the PACU (p = 0.009). In group S, the correlation between the severity of PS and the incidence of hypothermia (φc = 0.414, p = 0.121) was moderate but not significant. In group R, the correlation between PS severity and hypothermia (φc = 0.418, p = 0.043) was moderate and significant. Conclusions: Remimazolam showed better results than sevoflurane in anesthesia maintenance regarding hypothermia and PS.
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Hipotermia , Laparoscopía , Humanos , Femenino , Hipotermia/etiología , Sevoflurano/efectos adversos , Tiritona , Remifentanilo , Estudios Prospectivos , Anestesia General/efectos adversos , Laparoscopía/efectos adversos , Procedimientos Quirúrgicos Ginecológicos/efectos adversosRESUMEN
Protein extraction and digestion are important analytical steps in the study of proteomics. The use of sodium dodecyl sulfate (SDS) buffer makes it possible to effectively analyze various proteins. Its use was evaluated using the S-Trap digestion method and compared to the traditional In solution digestion method. Differences in protein composition were examined for each protein preparation method. S-Trap digestion followed by SDS buffer extraction clearly increased the number of identified proteins, including more mitochondrial and membrane-related proteins. The S-Trap digestion method with 5% SDS buffer was applied to the pellet remaining from the removal of RIPA buffer-soluble proteins, which identified more extracellular space proteins than the conventional S-Trap digestion method. S-Trap digestion of the pellet was particularly advantageous for identifying proteins located inside multilayer membranes.
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Proteínas/metabolismo , Proteómica/métodos , Animales , Línea Celular Tumoral , Espectrometría de Masas , Ratones , Péptidos/metabolismo , SolucionesRESUMEN
BACKGROUND: Dabie bandavirus, also termed as severe fever with thrombocytopenia syndrome virus (SFTSV), was first isolated in China in 2010. At this time, the virus was found to have spread to South Korea, Japan, and other countries. A high case fatality rate is reported for SFTS, ranging from 12-50% within various sources. Several omics for clinical studies among SFTS patients as well as studies of cultured SFTSV have attempted to characterize the relevant molecular biology and epidemiology of the disease. However, a global serum proteomics analysis among SFTS patients has not yet been reported to date. METHODS: In the current study, we evaluated comparative serum proteomics among SFTS patients (eight recovered patients and three deceased patients) with the goal of identifying the protein expression patterns associated with the clinical manifestations of SFTS. RESULTS: The proteomic results in the current study showed that the coagulation factor proteins, protein S and protein C, were statistically significantly downregulated among the deceased patients. Downregulation of the complement system as well as prolonged neutrophil activation were also observed. Additionally, the downstream proteins of tumour necrosis factor alpha, neutrophil-activating cytokine, and interleukin-1ß, an inflammatory cytokine, were overexpressed. CONCLUSIONS: Thrombocytopenia and multiple organ failure are the major immediate causes of death among SFTS patients. In this study, serum proteomic changes related to thrombocytopenia, abnormal immune response, and inflammatory activation were documented in SFTS patients. These findings provide useful information for understanding the clinical manifestations of SFTS.
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BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging infectious virus which causes severe hemorrhage, thrombocytopenia, and leukopenia, with a high fatality rate. Since there is no approved therapeutics or vaccines for SFTS, early diagnosis is essential to manage this infectious disease. METHODS: Here, we tried to detect SFTS virus in serum samples from SFTS patients by proteomic analysis. Firstly, in order to obtain the reference MS/MS spectral data of SFTS virus, medium from infected Vero cell culture was used for shotgun proteomic analysis. Then, tryptic peptides in sera from SFTS patients were confirmed by comparative analysis with the reference MS/MS spectral data of SFTS virus. RESULTS: Proteomic analysis of culture medium successfully discovered tryptic peptides from all the five antigen proteins of SFTS virus. The comparative spectral analysis of sera of SFTS patients revealed that the N-terminal tryptic peptide of the nucleocapsid (N) protein is the major epitope of SFTS virus detected in the patient samples. The prevalence of the peptides was strongly correlated with the viral load in the clinical samples. CONCLUSIONS: Proteomic analysis of SFTS patient samples revealed that nucleocapsid (N) protein is the major antigen proteins in sera of SFTS patients and N-terminal tryptic peptide of the N protein might be a useful proteomic target for direct detection of SFTS virus. These findings suggest that proteomic analysis could be an alternative tool for detection of pathogens in clinical samples and diagnosis of infectious diseases.
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Rapid and precise diagnostic methods are required to control emerging infectious diseases effectively. Human body fluids are attractive clinical samples for discovering diagnostic targets because they reflect the clinical statuses of patients and most of them can be obtained with minimally invasive sampling processes. Body fluids are good reservoirs for infectious parasites, bacteria, and viruses. Therefore, recent clinical proteomics methods have focused on body fluids when aiming to discover human- or pathogen-originated diagnostic markers. Cutting-edge liquid chromatography-mass spectrometry (LC-MS)-based proteomics has been applied in this regard; it is considered one of the most sensitive and specific proteomics approaches. Here, the clinical characteristics of each body fluid, recent tandem mass spectroscopy (MS/MS) data-acquisition methods, and applications of body fluids for proteomics regarding infectious diseases (including the coronavirus disease of 2019 [COVID-19]), are summarized and discussed.
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Cromatografía Liquida/métodos , Enfermedades Transmisibles/diagnóstico , Espectrometría de Masas/métodos , Técnicas Microbiológicas/métodos , Proteómica/métodos , Líquidos Corporales , Prueba de COVID-19/métodos , Humanos , Espectrometría de Masas en TándemRESUMEN
Immunoprofiling has an established impact on the prognosis of several cancers; however, its role and definition in high-grade serous ovarian cancer (HGSOC) are mostly unknown. This study is to investigate immunoprofiling which could be a prognostic factor in HGSOC. We produced tumor microarrays of 187 patients diagnosed with HGSOC. We performed a multiplexed immunofluorescence staining using Opal Multiplex IHC kit and quantitative analysis with Vectra-Inform system. The expression intensities of programmed death-ligand 1 (PD-L1), CD4, CD8, CD20, FoxP3, and CK in whole tumor tissues were evaluated. The enrolled patients showed general characteristics, mostly FIGO stage III/IV and responsive to chemotherapy. Each immune marker showed diverse positive densities, and each tumor sample represented its immune characteristics as an inflamed tumor or noninflamed tumor. No marker was associated with survival as a single one. Interestingly, high ratios of CD8 to FoxP3 and CD8 to PD-L1 were related to the favorable overall survival (77 vs. 39 months, 84 vs. 47 months, respectively), and CD8 to PD-L1 ratio was also a significant prognostic factor (HR 0.621, 95% CI 0.420-0.917, p = 0.017) along with well-known clinical prognostic factors. Additionally, CD8 to PD-L1 ratio was found to be higher in the chemosensitive group (p = 0.034). In conclusion, the relative expression levels of CD8, FoxP3, and PD-L1 were significantly related to the clinical outcome of patients with HGSOC, which could be a kind of significant immunoprofiling of ovarian cancer patients to apply for treatment.
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Biomarcadores de Tumor/análisis , Cistadenocarcinoma Seroso/metabolismo , Técnica del Anticuerpo Fluorescente/métodos , Neoplasias Ováricas/metabolismo , Coloración y Etiquetado/métodos , Adulto , Anciano , Antígeno B7-H1/análisis , Antígenos CD8/análisis , Cistadenocarcinoma Seroso/diagnóstico , Femenino , Factores de Transcripción Forkhead/análisis , Humanos , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Neoplasias Ováricas/diagnóstico , Pronóstico , Análisis de SupervivenciaRESUMEN
Scrub typhus, the third most frequently reported infectious disease in South Korea, causes serious public health problems. In 2019, we collected a bile specimen from a patient with scrub typhus through percutaneous transhepatic gallbladder drainage and performed transmission electron microscopy to confirm the ultrastructure of Orientia tsutsugamushi.
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Orientia tsutsugamushi , Tifus por Ácaros , Bilis , Humanos , Microscopía Electrónica de Transmisión , Orientia , Orientia tsutsugamushi/genética , República de Corea , Tifus por Ácaros/diagnósticoRESUMEN
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease in the world. Advanced glycation end products (AGEs) are thought to be involved in the pathogenesis of DN via multifactorial mechanisms including the generation of oxidative stress and overproduction of various growth factors and cytokines. AGEs are heterogeneous cross-linked sugar-derived proteins, and Nε-(carboxymethyl)-lysine (CML)-conjugated BSA is a major component of AGEs. However, the proteins involved in DN induction by CML have never been reported. Herein, we investigated specific protein regulators of AGE-mediated DN via proteomic analysis of streptozotocin (STZ)-induced diabetic mice kidneys. We identified 937, 976, and 870 proteins in control, STZ, and STZ + CML-BSA samples, respectively. Bioinformatics analysis identified several CML-mediated proteins potentially involved in kidney damage, activation of fatty acid oxidation (FAO), and mitochondrial dysfunction. Furthermore, we identified the CML-specific differential protein carnitine palmitoyltransferase 2 (CPT2), related to FAO. To confirm the effect of CPT2 and the CML-mediated mechanism, human renal tubular HK-2 cells were treated with CML-BSA and cpt2 siRNA, and examined for FAO-mediated fibrosis and mitochondrial dysfunction. CML-BSA and CPT2 knockdown induced fibrosis-related gene expression and damage to mitochondrial membrane potential. Moreover, CPT2 overexpression recovered CML-induced fibrosis-related gene expression. Based on these results, a decrease in CML-induced CPT2 expression causes mitochondrial FAO damage, leading to renal fibrosis and DN.