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1.
Metabolism ; 159: 155982, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39089491

RESUMEN

BACKGROUND: Receptor-interacting protein kinase (RIPK)3 is an essential molecule for necroptosis and its role in kidney fibrosis has been investigated using various kidney injury models. However, the relevance and the underlying mechanisms of RIPK3 to podocyte injury in albuminuric diabetic kidney disease (DKD) remain unclear. Here, we investigated the role of RIPK3 in glomerular injury of DKD. METHODS: We analyzed RIPK3 expression levels in the kidneys of patients with biopsy-proven DKD and animal models of DKD. Additionally, to confirm the clinical significance of circulating RIPK3, RIPK3 was measured by ELISA in plasma obtained from a prospective observational cohort of patients with type 2 diabetes, and estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR), which are indicators of renal function, were followed up during the observation period. To investigate the role of RIPK3 in glomerular damage in DKD, we induced a DKD model using a high-fat diet in Ripk3 knockout and wild-type mice. To assess whether mitochondrial dysfunction and albuminuria in DKD take a Ripk3-dependent pathway, we used single-cell RNA sequencing of kidney cortex and immortalized podocytes treated with high glucose or overexpressing RIPK3. RESULTS: RIPK3 expression was increased in podocytes of diabetic glomeruli with increased albuminuria and decreased podocyte numbers. Plasma RIPK3 levels were significantly elevated in albuminuric diabetic patients than in non-diabetic controls (p = 0.002) and non-albuminuric diabetic patients (p = 0.046). The participants in the highest tertile of plasma RIPK3 had a higher incidence of renal progression (hazard ratio [HR] 2.29 [1.05-4.98]) and incident chronic kidney disease (HR 4.08 [1.10-15.13]). Ripk3 knockout improved albuminuria, podocyte loss, and renal ultrastructure in DKD mice. Increased mitochondrial fragmentation, upregulated mitochondrial fission-related proteins such as phosphoglycerate mutase family member 5 (PGAM5) and dynamin-related protein 1 (Drp1), and mitochondrial ROS were decreased in podocytes of Ripk3 knockout DKD mice. In cultured podocytes, RIPK3 inhibition attenuated mitochondrial fission and mitochondrial dysfunction by decreasing p-mixed lineage kinase domain-like protein (MLKL), PGAM5, and p-Drp1 S616 and mitochondrial translocation of Drp1. CONCLUSIONS: The study demonstrates that RIPK3 reflects deterioration of renal function of DKD. In addition, RIPK3 induces diabetic podocytopathy by regulating mitochondrial fission via PGAM5-Drp1 signaling through MLKL. Inhibition of RIPK3 might be a promising therapeutic option for treating DKD.

2.
Nat Commun ; 15(1): 6680, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107284

RESUMEN

Synergistic combinations of immunotherapeutic agents can improve the performance of anti-cancer therapies but may lead to immune-mediated adverse effects. These side-effects can be overcome by using a tumor-specific delivery system. Here, we report a method of targeted immunotherapy using an attenuated Salmonella typhimurium (SAM-FC) engineered to release dual payloads: cytolysin A (ClyA), a cytolytic anti-cancer agent, and Vibrio vulnificus flagellin B (FlaB), a potent inducer of anti-tumor innate immunity. Localized secretion of ClyA from SAM-FC induces immunogenic cancer cell death and promotes release of tumor-specific antigens and damage-associated molecular patterns, which establish long-term antitumor memory. Localized secretion of FlaB promotes phenotypic and functional remodeling of intratumoral macrophages that markedly inhibits tumor metastasis in mice bearing tumors of mouse and human origin. Both primary and metastatic tumors from bacteria-treated female mice are characterized by massive infiltration of anti-tumorigenic innate immune cells and activated tumor-specific effector/memory T cells; however, the percentage of immunosuppressive cells is low. Here, we show that SAM-FC induces functional reprogramming of the tumor immune microenvironment by activating both the innate and adaptive arms of the immune system and can be used for targeted delivery of multiple immunotherapeutic payloads for the establishment of potent and long-lasting antitumor immunity.


Asunto(s)
Inmunoterapia , Salmonella typhimurium , Microambiente Tumoral , Animales , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Salmonella typhimurium/inmunología , Salmonella typhimurium/efectos de los fármacos , Femenino , Ratones , Humanos , Inmunoterapia/métodos , Línea Celular Tumoral , Inmunidad Innata/efectos de los fármacos , Ratones Endogámicos C57BL , Flagelina/inmunología , Vibrio vulnificus/inmunología , Vibrio vulnificus/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación
3.
Antibiotics (Basel) ; 13(7)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39061308

RESUMEN

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary and require safety evaluations, including antibiotic resistance, before use as a starter. In this research, we investigated the antibiotic resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter, against 10 different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study.

5.
World J Gastrointest Oncol ; 16(7): 2925-2940, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39072168

RESUMEN

BACKGROUND: Little is known about disparities in diagnosis and treatment among colorectal cancer (CRC) patients with and without disabilities. AIM: To investigate the patterns of diagnosis, treatment, and survival for people with and without disabilities who had CRC. METHODS: We performed a retrospective analysis using the Korean National Health Insurance Service database, disability registration data, and Korean Central Cancer Registry data. The analysis included 21449 patients with disabilities who were diagnosed with CRC and 86492 control patients diagnosed with CRC. RESULTS: The overall distribution of CRC stage was not affected by disability status. Subjects with disabilities were less likely than those without disabilities to undergo surgery [adjusted odds ratio (aOR): 0.85; 95% confidence interval (95%CI): 0.82-0.88], chemotherapy (aOR: 0.84; 95%CI: 0.81-0.87), or radiotherapy (aOR: 0.90; 95%CI: 0.84-0.95). The rate of no treatment was higher in patients with disabilities than in those without disabilities (aOR: 1.48; 95%CI: 1.41-1.55). The overall mortality rate was higher in patients with disabilities [adjusted hazard ratio (aHR): 1.24; 95%CI: 1.22-1.28], particularly severe disabilities (aHR: 1.57; 95%CI: 1.51-1.63), than in those without disabilities. CONCLUSION: Patients with severe disabilities tended to have a late or unknown diagnosis. Patients with CRC and disabilities had lower rates of treatment with almost all modalities compared with those without disabilities. During the follow-up period, the mortality rate was higher in patients with disabilities than in those without disabilities. The diagnosis and treatment of CRC need improvement in patients with disabilities.

6.
J Clin Med ; 13(11)2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38892847

RESUMEN

Objective: Previous studies have reported controversial results on the association between gout and the risk of cancer. This study aimed to investigate the relationship between gout and the incidence of head and neck cancer (HNC). Methods: The data of participants who underwent health checkups in 2009 were analyzed using the National Health Insurance Database in South Korea. A total of 14,348 HNC patients and 57,392 control participants were analyzed for a prior history of gout. Overlap weighting was applied, and odds ratios (ORs) of gout for HNC patients were analyzed. The overlap-weighted model adjusted for demographic, socioeconomic, and lifestyle factors and comorbidities. HNC sites were classified as oral cavity cancer, oropharyngeal cancer, nasopharyngeal cancer, hypopharyngeal cancer, nasal cavity/sinus cancer, larynx cancer, or salivary gland cancer, and the ORs of gout were estimated for each site. Results: Overall, patients with HNC had 1.12-fold greater odds of having gout (95% confidence intervals [CIs] = 1.04-1.20). According to the site of HNC, oral cavity cancer, oropharynx cancer, and larynx cancer demonstrated high odds of having gout (OR = 1.25, 95% CI = 1.16-1.34 for oral cavity cancer; OR = 1.08, 95% CI = 1.01-1.15 for oropharynx cancer; and OR = 1.12, 95% CI = 1.06-1.20 for larynx cancer). On the other hand, nasal cavity/sinus cancer, nasopharynx cancer, and salivary gland cancer presented low odds of having gout (OR = 0.78, 95% CI = 0.72-0.84 for nasal cavity/sinus cancer; OR = 0.89, 95% CI = 0.83-0.96 for nasopharynx cancer; and OR = 0.88, 95% CI = 0.81-0.96 for salivary gland cancer). Conclusions: A prior history of gout was associated with a high overall incidence of HNC. Oral cavity cancer, oropharynx cancer, and larynx cancer have a high incidence in gout patients. However, nasal cavity/sinus cancer, nasopharyngeal cancer, and salivary gland cancer have low incidences in gout patients. The impact of gout on HNC risk should be specifically considered according to the site of the HNC.

7.
World Allergy Organ J ; 17(6): 100907, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38873616

RESUMEN

Background: Asthma has been suggested to be a risk factor for cardiovascular diseases (CVDs), although the evidence supporting this relationship is inconclusive. This study aimed to explore the long-term associations between asthma and asthma exacerbations with the occurrence of cardiovascular diseases (CVDs) such as ischemic heart disease (IHD), heart failure (HF), and cerebral stroke, utilizing data from a nationwide cohort. Materials and methods: This study utilized data from the Korean National Health Insurance Service-Health Screening Cohort database (2002-2015), including information on 111,316 asthma patients and an equal number of 1:1 matched control participants. A propensity score overlap-weighted Cox proportional hazards regression model was used to analyze the overlap-weighted hazard ratios (HRs) of asthma and exacerbated asthma for cardiovascular diseases (CVDs) within this cohort. Results: During the follow-up period, the incidence rate (IR) of IHD per 1000 person-years (PYs) was 7.82 in patients with asthma and 5.79 in controls. The IR of HF was 2.53 in asthmatic patients and 1.36 in controls. After adjustment for covariates, asthmatic patients exhibited 1.27-fold and 1.56-fold higher HRs for IHD (95% confidence interval (CI) = 1.23-1.37, P < 0.001) and HF (95% CI = 1.36-1.63, P < 0.001) than the controls, respectively. In addition, there was an increased HR for IHD and HF in the asthma exacerbation group compared with the nonexacerbated asthma group (adjusted HR, 1.29, 95% CI = 1.24-1.34, P < 0.001 for IHD and aHR 1.68, 95% CI = 1.58-1.79, P < 0.001 for HF). However, the occurrence of stroke was decreased in asthmatic patients compared with controls (aHR = 0.96, 95% CI = 0.93-0.99, P = 0.008). Conclusions: Adults with asthma are more likely to develop CVDs. Additionally, severe asthma exacerbations are significantly associated with an increased occurrence of CVDs.

8.
BMJ Open Respir Res ; 11(1)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38897613

RESUMEN

BACKGROUND: Existing studies on chronic obstructive pulmonary disease (COPD) in Korea lack full population coverage, relying on small sample sizes. Therefore, this study aims to investigate the prevalence and mortality of COPD in the entire Korean population. METHODS: This serial cross-sectional study used national databases, linking the National Health Information Database (2008-2017) with Causes of Death Statistics. Identification of individuals with COPD used diagnostic codes (International Classification of Diseases-10: J41-J44) or a history of COPD-related hospitalisation, focusing on adults aged 40 and above. Prevalence and mortality rates, calculated for 2008-2017, encompassed both crude and age-standardised and sex-standardised measures. A multivariate Poisson regression model estimated the association between COPD and all-cause and cause-specific mortality, presenting incidence rate ratios (IRRs) and 95% CIs, using data from the year 2017. RESULTS: Age-adjusted COPD prevalence exhibited a notable increase from 2008 (7.9%) to 2017 (16.7%) in both sexes. The prevalences of diabetes mellitus, hypertension, dyslipidaemia, ischaemic heart disease, cancer, osteoporosis and tuberculosis were higher in the COPD group than in the group without COPD (p for all <0.001). The incidence of stroke and myocardial infarction (p for all <0.001) and overall mortality were higher in the COPD group (adjusted IRR 1.23, 95% CI 1.22 to 1.24, p<0.001). In particular, incidence rate and risk of mortality due to lung cancer were higher than that of those without COPD compared with other cancer types (adjusted IRR 2.51, 95% CI 2.42 to 2.60, p<0.001). It was significantly higher the incidence rate and risk of mortality among group with COPD than those without COPD in lower respiratory disease (adjusted IRR 16.62, 95% CI 15.07 to 18.33, p<0.001), asthma (adjusted IRR 6.41, 95% CI 5.47 to 7.51, p<0.001) and bronchiectasis (adjusted IRR 11.77, 95% CI 7.59 to 18.26, p<0.001), respectively. DISCUSSION: Our study showed that the prevalence of COPD is gradually increasing from 9.2% in 2009 to 16.7% in 2018. Furthermore, in overall (all-cause) mortality, it was significantly higher in group with COPD than in group without COPD. The mortality rate of group with COPD was much higher than the overall mortality rate but is gradually decreasing.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , República de Corea/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Prevalencia , Anciano , Estudios Transversales , Adulto , Anciano de 80 o más Años , Causas de Muerte , Incidencia , Bases de Datos Factuales
9.
J Hepatol ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38879170

RESUMEN

BACKGROUND & AIMS: Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. METHODS: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. RESULTS: The Treg cell population - especially the activated Treg cell subpopulation - was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS: Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

10.
Laryngoscope ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38828668

RESUMEN

OBJECTIVE: The goal of the present study was to estimate the risk of hearing impairment in patients with COPD using huge nationwide population. METHODS: A retrospective case-control study was performed using the National Health Insurance Database in South Korea from 2002 through 2019. Totally 614,370 COPD patients and matched 2,170,504 control participants were selected at a 1:4 ratio. Hearing impairment was defined based on the registered data in the Ministry of Health and Welfare of Korea with six levels of severity of hearing impairment. The propensity score was calculated, and overlap-weighted multinomial logistic regression was used to calculate the odds ratios of COPD for hearing impairment. RESULTS: A total of 2.67% of COPD patients and 1.9% of control participants had hearing impairment. The COPD patients indicated 1.10-1.21 times higher odds for hearing impairment according to the severity of hearing impairment than the control group. In accordance with age and sex, the younger age group (<65 years old) and female group demonstrated higher odds for hearing impairment related to the presence of COPD. The high odds for hearing impairment in patients with COPD was consistent in all other subgroups, except for the underweight group. CONCLUSIONS: COPD was associated with an increased risk of hearing impairment in the general population in Korea. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

11.
iScience ; 27(5): 109675, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38706837

RESUMEN

Corticotropin-releasing hormone (CRH) is a key mediator in stress-induced hair growth inhibition. Here, we investigated the impact of stress-induced senescence and evaluated the potential of Ganoderma lucidum (GL) extract in mitigating CRH-induced senescence in human hair follicle cells (hHFCs). We show that CRH treatment increased the senescence-associated beta-galactosidase (SA-ß-GAL) activity and reactive oxygen species (ROS) formation in hHFCs and suppressed alkaline phosphatase (ALP) activity and anagen-inducing genes. However, GL extract restored ALP activity and decreased the expression levels of anagen-related genes in CRH-treated hHFCs. It decreased SA-ß-GAL activity, reduced ROS production, and prevented the phosphorylation of MAPK signaling pathways in CRH-related stress response. Moreover, GL reversed the CRH-induced inhibition of two-cell assemblage (TCA) elongation and Ki67 expression. GL extract attenuates stress-induced hair follicular senescence by delaying catagen entry and scavenging ROS. Our findings suggest that GL extract could be used for treating stress-induced hair loss.

12.
Proc Natl Acad Sci U S A ; 121(22): e2404007121, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38768347

RESUMEN

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.


Asunto(s)
Tacto , Realidad Virtual , Tecnología Inalámbrica , Humanos , Tecnología Inalámbrica/instrumentación , Tacto/fisiología , Piel , Robótica/instrumentación , Robótica/métodos
13.
Br J Cancer ; 130(12): 1979-1989, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38643339

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+/IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+/IL-22R1+ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated. RESULTS: IL-10R2+/IL-22R1+ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2+ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2+/IL-22R1+ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2+/IL-22R1+ myeloid cells. IL-10R2+/IL-22R1+ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2+ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients. CONCLUSIONS: IL-10R2+/IL-22R1+ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.


Asunto(s)
Biomarcadores de Tumor , Carcinoma Ductal Pancreático , Subunidad beta del Receptor de Interleucina-10 , Células Mieloides , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas , Receptores de Interleucina , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/sangre , Humanos , Animales , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/sangre , Ratones , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Receptores de Interleucina/genética , Células Mieloides/metabolismo , Células Mieloides/patología , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Subunidad beta del Receptor de Interleucina-10/genética , Femenino , Masculino , Microambiente Tumoral/genética , Línea Celular Tumoral
14.
J Clin Med ; 13(8)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38673440

RESUMEN

Background/Introduction: Odontogenic infection is one of the main etiologies of deep neck infection (DNI). However, the relationship between chronic periodontitis (CP) and the incidence of DNI has not been examined. This study aimed to evaluate the incidence of DNI and peritonsillar abscess (PTA) after CP. Methods: The Korean National Health Insurance Service-National Sample Cohort 2002-2019 was used. In Study I, 4585 PTA patients were matched with 19,340 control I participants. A previous history of CP for 1 year was collected, and the odds ratios (ORs) of CP for PTA were analyzed using conditional logistic regression. In Study II, 46,293 DNI patients and 185,172 control II participants were matched. A previous history of CP for 1 year was collected, and conditional logistic regression was conducted for the ORs of CP for DNI. Secondary analyses were conducted in demographic, socioeconomic, and comorbidity subgroups. Results: In Study I, a history of CP was not related to the incidence of PTA (adjusted OR = 1.28, 95% confidence interval [CI] = 0.91-1.81). In Study II, the incidence of DNI was greater in participants with a history of CP (adjusted OR = 1.55, 95% CI = 1.41-1.71). The relationship between CP history and DNI was greater in groups with young, male, low-income, and rural residents. Conclusions: A prior history of CP was associated with a high incidence of DNI in the general population of Korea. Patients with CP need to be managed for the potential risk of DNI.

15.
Korean J Ophthalmol ; 38(3): 194-202, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38584440

RESUMEN

PURPOSE: To determine subjective symptoms and medical history of patients with intermittent exotropia in a large study population. METHODS: The Korean Intermittent Exotropia Multicenter Study (KIEMS) is a nationwide, observational, cross-sectional, multicenter study conducted by the Korean Association for Pediatric Ophthalmology and Strabismus including 5,385 patients with intermittent exotropia. Subjective symptoms and medical history of patients with intermittent exotropia were extracted by a comprehensive survey based on a self-administered questionnaire according to the study protocol of the KIEMS. RESULTS: The mean age of symptom onset was 5.5 years. The most common symptom reported in patients with intermittent exotropia was photophobia (52.1%), followed by diplopia at near fixation (7.3%) and distance fixation (6.2%). Preterm birth was found in 8.8%, and 4.1% had perinatal complications. A family history of strabismus was present in 14.9%, and 5.5% of patients had a family member who underwent strabismus surgery. CONCLUSIONS: The KIEMS is one of the largest clinical studies on intermittent exotropia. Intermittent exotropia frequently caused photophobia and diplopia, and patients with a family history was not uncommon.


Asunto(s)
Exotropía , Autoinforme , Humanos , Exotropía/fisiopatología , Exotropía/diagnóstico , Exotropía/cirugía , Masculino , Femenino , Estudios Transversales , República de Corea/epidemiología , Niño , Preescolar , Encuestas y Cuestionarios , Adolescente , Adulto , Adulto Joven , Persona de Mediana Edad , Lactante
16.
Am J Pathol ; 194(7): 1306-1316, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38588851

RESUMEN

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin (mTOR) and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. Data from this study indicate that TFE3 plays a role in the PI3K/Akt pathway in RCC. The results of this study suggest that PI3K/Akt inhibitors may aid in the treatment of patients with RCC by affecting the tumor microenvironment.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Carcinoma de Células Renales , Neoplasias Renales , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Microambiente Tumoral , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/genética , Serina-Treonina Quinasas TOR/metabolismo , Microambiente Tumoral/fisiología , Neoplasias Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiología , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasas/metabolismo , Regulación Neoplásica de la Expresión Génica
17.
Nat Commun ; 15(1): 2129, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459042

RESUMEN

The development of advanced materials capable of autonomous self-healing and mechanical stimulus sensing in aquatic environments holds great promise for applications in underwater soft electronics, underwater robotics, and water-resistant human-machine interfaces. However, achieving superior autonomous self-healing properties and effective sensing simultaneously in an aquatic environment is rarely feasible. Here, we present an ultrafast underwater molecularly engineered self-healing piezo-ionic elastomer inspired by the cephalopod's suckers, which possess self-healing properties and mechanosensitive ion channels. Through strategic engineering of hydrophobic C-F groups, hydrolytic boronate ester bonds, and ions, the material achieves outstanding self-healing efficiencies, with speeds of 94.5% (9.1 µm/min) in air and 89.6% (13.3 µm/min) underwater, coupled with remarkable pressure sensitivity (18.1 kPa-1) for sensing performance. Furthermore, integration of this mechanosensitive device into an underwater submarine for signal transmission and light emitting diode modulation demonstrates its potential for underwater robotics and smarter human-machine interactions.

18.
Polymers (Basel) ; 16(6)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38543423

RESUMEN

We developed a series of Zn(II)-Co(III) double metal cyanide (DMC) catalysts with exceptional activity for the ring-opening polymerization of various cyclic monomers by employing diverse organophosphorus compounds as complexing agents (CAs). The chemical structure and composition of DMC catalysts were investigated by commonly used analysis such as infrared and X-ray photoelectron spectroscopies, and elemental analysis combining with in situ NMR analysis to determine the complexation types of organophosphorus compounds the catalyst framework. The resulting catalysts exhibited very high turnover frequencies (up to 631.4 min-1) in the ring-opening polymerization (ROP) of propylene oxide and good efficiency for the ROP of ε-caprolactone. The resultant polyester polyols are suitable to use as an macroinitiator to produce well-defined poly(ester ether) triblock copolymers of 1800-6600 g mol-1 and dispersity of 1.16-1.37. Additionally, the DMC catalysts bearing organophosphorus compounds CAs exhibited remarkable selectivity for the copolymerization of PO with CO2, yielding poly(ether carbonate) polyols with carbonate contents up to 34.5%. This study contributes to the development of efficient DMC catalytic systems that enable the synthesis of high-quality polyols for various applications.

19.
Biomedicines ; 12(3)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38540123

RESUMEN

Wound dressings are widely used to protect wounds and promote healing. The water absorption and antifriction properties of dressings are important for regulating the moisture balance and reducing secondary damages during dressing changes. Herein, we developed a hyaluronic acid (HA)-based foam dressing prepared via the lyophilization of photocrosslinked HA hydrogels with high water absorption and antiadhesion properties. To fabricate the HA-based foam dressing (HA foam), the hydroxyl groups of the HA were modified with methacrylate groups, enabling rapid photocuring. The resulting photocured HA solution was freeze-dried to form a porous structure, enhancing its exudate absorption capacity. Compared with conventional biopolymer-based foam dressings, this HA foam exhibited superior water absorption and antifriction properties. To assess the wound-healing potential of HA foam, animal experiments involving SD rats were conducted. Full-thickness defects measuring 2 × 2 cm2 were created on the skin of 36 rats, divided into four groups with 9 individuals each. The groups were treated with gauze, HA foam, CollaDerm®, and CollaHeal® Plus, respectively. The rats were closely monitored for a period of 24 days. In vivo testing demonstrated that the HA foam facilitated wound healing without causing inflammatory reactions and minimized secondary damages during dressing changes. This research presents a promising biocompatible foam wound dressing based on modified HA, which offers enhanced wound-healing capabilities and improved patient comfort and addresses the challenges associated with conventional dressings.

20.
Foods ; 13(6)2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38540946

RESUMEN

With increasing interest in Korean foods and beverages, Korean traditional alcoholic beverages need to be studied. To characterize Korean traditional alcoholic beverages, we analyzed the metabolites of Takju, Yakju, and Traditional-Soju using 48 commercial products. We performed non-targeted metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and identified 33 significantly discriminant metabolites, including nine organic acids, three amino acids, and seven fatty acids, in the three types of alcoholic beverage. Subsequently, we quantified the profiled metabolites in each product and compared their contents to identify alcoholic beverage type-specific metabolites. Thus, we figured out seven metabolites using receiver operating characteristic (ROC) curves. The results revealed that octadecanoic acid (limit of detection (LOD) to 168.72 mg/L), nonanoic acid (LOD to 112.54 mg/L), and octanoic acid (8.00 to 145.08 mg/L) in Takju; succinic acid (LOD to 1.90 mg/mL), heptanoic acid (LOD to 343.23 mg/L), and hexadecanoic acid (20.28 to 126.45 mg/L) in Yakju; and malonic acid (LOD to 19.13 mg/mL) in Traditional-Soju, with an area under the curve (AUC) > 0.7, are important metabolites that can distinguish the type of alcoholic beverage. Our results provide qualitative and quantitative metabolite information about Korean traditional alcoholic beverages that can be used by consumers and manufacturers.

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