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1.
J Ophthalmol ; 2024: 3654690, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220230

RESUMO

Purpose: This study aimed to evaluate the expression of microRNAs (miRNAs) and inflammasomes in diabetes-induced retinal cells and to determine their role in the pathogenesis of diabetic retinopathy (DR). Methods: To establish diabetes-induced cell models, ARPE-19 cells were treated with high glucose. The expression levels of five miRNAs (miR-185, miR-17, miR-20a, miR-15a, and miR-15b) were measured in high glucose-treated ARPE-19 cells using real-time quantitative polymerase chain reaction. Western blotting was performed to measure inflammasome expression in cellular models. miR-17 was selected as the target miRNA, and inflammasome expression was measured following the transfection of an miR-17 mimic into high glucose-treated ARPE-19 cells. Results: In high glucose-treated ARPE-19 cells, miRNA expression was substantially downregulated, whereas that of inflammasome components was significantly increased. Following the transfection of the miR-17 mimic into high glucose-treated ARPE-19 cells, the levels of inflammasome components were significantly decreased. Conclusions: This study investigated the relationship between miRNAs and inflammasomes in diabetes-induced cells using high glucose-treated ARPE-19 cells. These findings suggested that miR-17 suppresses inflammasomes, thereby reducing the subsequent inflammatory response and indicating that miRNAs and inflammasomes could serve as new therapeutic targets for DR.

2.
Korean J Med Educ ; 36(3): 327-333, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39246113

RESUMO

PURPOSE: This study aimed to investigate the difference in satisfaction and learning benefits between e-portfolios compared to paper portfolios during clinical practice in medical schools. METHODS: Utilization of and satisfaction with e-portfolios among 40 third-year medical students in the medicine department of Ajou University School of Medicine was collected using an online survey in December 2020. The collected data were analyzed using descriptive statistics and an analysis of variance. RESULTS: Students perceived that e-portfolios were highly beneficial for consistently documenting activities during clinical practice, when compared to paper-based portfolios (mean±standard deviation [SD]=2.60±1.22). However, the least rated aspect was that e-portfolios require less time than paper-based portfolios (mean±SD=1.80±1.14). Additionally, among the various clinical practice courses using e-portfolios, the highest satisfaction was observed with the fewest content items in the e-portfolio. CONCLUSION: To maximize the potential benefits of e-portfolios, improvements in implementation and usability are essential. Additionally, for effective utilization of e-portfolios in clinical practice, it is necessary to clearly define students' required competencies and ultimate goals, and structure content accordingly.


Assuntos
Educação de Graduação em Medicina , Avaliação Educacional , Aprendizagem , Satisfação Pessoal , Faculdades de Medicina , Estudantes de Medicina , Humanos , Inquéritos e Questionários , Avaliação Educacional/métodos , Feminino , Masculino , Competência Clínica , Documentação , Internet
3.
Biochem Pharmacol ; 229: 116520, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39236934

RESUMO

Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs. SphK1 was also increased in liver homogenates of carbon tetrachloride-treated or bile duct ligated mice and in transforming growth factor-ß (TGF-ß)-treated LX-2 cells. TGF-ß-mediated SphK1 induction was due to Smad3 signaling in LX-2 cells. SphK1 modulation altered the expression of liver fibrogenesis-related genes. This SphK1-mediated profibrogenic effect was dependent on SphK1/sphingosine-1-phosphate/sphingosine-1-phosphate receptor signaling through ERK. Epigallocatechin gallate blocked TGF-ß-induced SphK1 expression and hepatic fibrogenesis by attenuating Smad and MAPK activation. SphK1 induced by TGF-ß facilitates HSC activation and liver fibrogenesis, which is reversed by epigallocatechin gallate. Accordingly, SphK1 and related signal transduction may be utilized to treat liver fibrosis.

4.
Integr Med Res ; 13(3): 101071, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39263445

RESUMO

Background: Korean red ginseng extract (KRGE) (Family: Araliaceae) is one of the most widely used traditional herbs in Asia. Multiple studies have shown that KRGE has anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. Methods: Sprague-Dawley rats were divided into five groups for PTU-induced hypothyroidism and six groups for LT4-induced hyperthyroidism. At the experiment's conclusion, rats were sacrificed, and blood, thyroid gland, and liver samples were collected. Body weight was recorded weekly, and serum hormone levels were assessed using enzyme-linked immunoassay. Thyroid gland and liver tissues were stained with hematoxylin and eosin. KRGE was prepared in 0.5% CMC and stored at 4 °C before administration. Results: In the LT4-induced hyperthyroidism model, KRGE prevented decreases in body weight, thyroid gland weight, liver weight, serum glucose, and thyroid hormone levels compared to the PTU group. It also reduced increases in T3, T4, and serum aspartate aminotransferase levels after LT4 treatment. Additionally, KRGE improved thyroid gland and liver histopathology, effects not observed in the PTU-induced hypothyroidism model. Conclusion: All things considered, our research points to KRGE's potential protective role in rat hyperthyroidism caused by LT4 by lowering thyroid hormone production.

5.
Front Pharmacol ; 15: 1347622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295932

RESUMO

Background: Stroke, a leading cause of death and disability, lacks effective treatments. Post-stroke secondary damage worsens the brain microenvironment, further exacerbating brain injury. Microglia's role in responding to stroke-induced damage in peri-infarct regions is crucial. In this study, we explored Weisheng-tang's potential to enhance ischemic outcomes by targeting microglia. Methods: We induced middle cerebral artery occlusion and reperfusion in mice, followed by behavioral assessments and infarct volume analyses after 48 h, and examined the changes in microglial morphology through skeleton analysis. Results: Weisheng-tang (300 mg/kg) significantly reduced infarction volume and alleviated neurological and motor deficits. The number of activated microglia was markedly increased within the peri-infarct territory, which was significantly reversed by Weisheng-tang. Microglial morphology analysis revealed that microglial processes were retracted owing to ischemic damage but were restored in Weisheng-tang-treated mice. This restoration was accompanied by the expression of the purinergic P2Y12 receptor (P2Y12R), a key regulator of microglial process extension. Weisheng-tang increased neuronal Kv2.1 clusters while suppressing juxtaneuronal microglial activation. The P2Y12R inhibitor-ticagrelor-eliminated the tissue and functional recovery that had been observed with Weisheng-tang after ischemic damage. Discussion: Weisheng-tang improved experimental stroke outcomes by modulating microglial morphology through P2Y12R, shedding light on its neuroprotective potential in ischemic stroke.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39237150

RESUMO

BACKGROUND: Cryptogenic new-onset refractory status epilepticus (cNORSE) currently lacks comprehensive knowledge regarding its clinical dynamics, prognostic factors and treatment guidance. Here we present the longitudinal clinical profiles, predictive factors for outcomes and the optimal duration of immunotherapy in patients with cNORSE. METHODS: This retrospective secondary endpoint analysis investigated patients with cNORSE identified from a prospective autoimmune encephalitis cohort at a national referral centre in Korea. The main outcomes included longitudinal functional scales, seizure frequency and the number of antiseizure medications. Measures encompassed NORSE-related clinical parameters such as the duration of unconsciousness, immunotherapy profiles, cytokine/chemokine analysis, and serial MRI scans. RESULTS: A total of 74 patients with cNORSE were finally analysed (mean age: 38.0±18.2; 36 (48.6%) male). All patients received first-line immunotherapy, and 91.9% (68/74) received second-line immunotherapy. A total of 83.8% (62/74) regained consciousness within a median duration of 30 days (14-56), and 50% (31/62) achieved good outcome (mRS ≤2) at 2 years. Poor 1-year outcomes (mRS ≥3) were predicted by the presence of mesial temporal lobe (mTL) and extra-mTL lesions at 3-month MRI, and prolonged unconsciousness (≥60 days). Those with mTL atrophy exhibited a higher seizure burden post-NORSE. The optimal duration of immunotherapy appeared to be between 18 weeks and 1-year post-NORSE onset. CONCLUSIONS: This study elucidates longitudinal clinical dynamics, functional outcomes, prognostic factors and immunotherapy response in patients with cNORSE. These findings might contribute to a more standardised understanding and clinical decision-making for cNORSE.

7.
Retina ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39151202

RESUMO

PURPOSE: To assess the longitudinal surgical outcomes of macular telangiectasia type 2 macular hole (MacTel-MH) and compare them with those of idiopathic MH. METHODS: This retrospective, single-tertiary center study included patients who underwent MH surgery between January 2015 and September 2023. Patients with characteristic optical coherence tomography (OCT) findings of MacTel in both eyes or those who underwent fluorescence angiography were classified as having MacTel MH. Baseline and postoperative best-corrected visual acuity and OCT parameters were reviewed. RESULTS: Totally, 27 and 243 eyes with MacTel and idiopathic MH, respectively, were included. MH closure rate was better achieved in idiopathic than in MacTel MH group at 2 years postoperatively. Temporal recovery of ellipsoid zone and external limiting membrane was more prominent in MacTel than in idiopathic MH group. Statistically significant visual acuity improvement was seen between 3 months and 2 years postoperatively in MacTel MH group. CONCLUSION: To the best of our knowledge, this is the first study to analyze the surgical outcomes of MacTel MH in both anatomical and functional aspects and compare them with patients with idiopathic MH. Postoperative microglia change would have affected the restoration of outer retinal layer of patients; however, further studies are needed for clarification.

8.
J Clin Invest ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39190624

RESUMO

The burden of senescent hepatocytes correlates with MASLD severity but mechanisms driving senescence, and how it exacerbates MASLD are poorly understood. Hepatocytes become senescent when Smoothened (Smo) is deleted to disrupt Hedgehog signaling. We aimed to determine if the secretomes of Smo-deficient hepatocytes perpetuate senescence to drive MASLD progression. RNA seq analysis confirmed that hepatocyte populations of MASLD livers are depleted of Smo(+) cells and enriched with senescent cells. When fed CDA-HFD, Smo(-) mice had lower antioxidant markers and developed worse DNA damage, senescence, MASH and liver fibrosis than Smo(+) mice. Sera and hepatocyte-conditioned medium from Smo(-) mice were depleted of thymidine phosphorylase (TP), a protein that maintains mitochondrial fitness. Treating Smo(-) hepatocytes with TP reduced senescence and lipotoxicity; inhibiting TP in Smo(+) hepatocytes had the opposite effects and exacerbated hepatocyte senescence, MASH, and fibrosis in CDA-HFD-fed mice. Therefore, we found that inhibiting Hedgehog signaling in hepatocytes promotes MASLD by suppressing hepatocyte production of proteins that prevent lipotoxicity and senescence.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39199016

RESUMO

OBJECTIVE: Leucine-rich glioma-inactivated 1 (LGI1)-antibody encephalitis (LGI1e), the major form of autoimmune encephalitis (AE) presented with memory loss and faciobrachial dystonic seizure, commonly develops in aged population. Hematologic aging is often accompanied by clonal hematopoiesis (CH), a phenomenon in which specific mutations accumulate, potentially leading to autoimmune disorders or malignancies. Our research aimed to investigate the connection between clonal hematopoiesis of indeterminate potential (CHIP) and LGI1e. METHODS: Peripheral blood samples from consecutive LGI1e patients were collected and analyzed for 24 clonal CHIP using targeted gene sequencing. The results were compared to a control dataset from an ethnically matched health care cohort. Patient characteristics were analyzed based on their CHIP status. RESULTS: A total of 52 LGI1e patients were enrolled for this study. Among them, three patients (5.8%) exhibited functional mutations in the ASXL1 gene, one of the CHIP-associated genes analyzed by targeted sequencing. This frequency was significantly higher compared to that of the control cohort (1%, p = 0.015). Nevertheless, the patients showed no difference in the clinical characteristics, laboratory results, and immunotherapy outcomes. INTERPRETATION: LGI1e showed high frequency of ASXL1 functional mutation in the CHIP analysis, which may contribute to the underlying pathogenesis. Further research is needed to determine its direct role in the development of autoimmunity and disease progression.

10.
Skin Res Technol ; 30(8): e13908, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39141418

RESUMO

BACKGROUND: Classifying diverse skin types is crucial for promoting skin health. However, efficiently identifying and analyzing relevant biomarkers from a vast array of available genetic data is challenging. Therefore, this study aimed to develop a precise and efficient platform for analyzing specific skin biomarkers using quantitative real-time PCR (qRT-PCR) with the minimal invasive skin sampling method (MISSM). MATERIALS AND METHODS: MISSM was used for RNA extraction from skin samples, followed by qRT-PCR analysis to quantify the expression of 20 biomarkers associated with skin characteristics (four biomarkers each for five skin characteristics). Noninvasive measurements from 299 Korean participants were utilized to correlate biomarker expression with skin parameters. Statistical analyses were conducted between biomarker expression levels and noninvasive skin measurements to select the relatively best-performing biomarker for each skin characteristic. RESULTS: Collagen type 1 alpha 1 (COL1A1) and moesin (MSN) were identified as skin aging biomarkers. Krüppel-like factor 4 (KLF4) and serine peptidase inhibitor Kazal type 5 (SPINK5) were identified as skin dryness biomarkers, whereas melan-A (MLANA) was selected as a biomarker for understanding pigmentation dynamics. Myelin protein zero like 3 (MPZL3) and high mobility group box 2 (HMGB2) were identified as markers of oily skin and skin sensitivity, respectively. Statistically significant correlations were found between the biomarker expression levels and noninvasive skin characteristic measurements. CONCLUSION: This study successfully developed a platform for the precise evaluation of individual skin characteristics using MISSM and qRT-PCR biomarker analysis. By selecting biomarkers that correlate with noninvasive measurements of skin characteristics, we demonstrated the platform's efficacy in assessing diverse skin conditions.


Assuntos
Biomarcadores , Fator 4 Semelhante a Kruppel , Reação em Cadeia da Polimerase em Tempo Real , Envelhecimento da Pele , Pele , Humanos , Biomarcadores/metabolismo , Biomarcadores/análise , Feminino , Masculino , Reação em Cadeia da Polimerase em Tempo Real/métodos , Pele/metabolismo , Adulto , Pessoa de Meia-Idade , Envelhecimento da Pele/genética , Envelhecimento da Pele/fisiologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Idoso , Adulto Jovem
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 323: 124912, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39142263

RESUMO

In recent years, hyperspectral imaging combined with machine learning techniques has garnered significant attention for its potential in assessing fruit maturity. This study proposes a method for predicting strawberry fruit maturity based on the harvest time. The main features of this study are as follows. 1) Selection of wavelength band associated with strawberry growth season; 2) Extraction of efficient parameters to predict strawberry maturity 3) Prediction of internal quality attributes of strawberries using extracted parameters. In this study, experts cultivated strawberries in a controlled environment and performed hyperspectral measurements and organic analyses on the fruit with minimal time delay to facilitate accurate modeling. Data augmentation techniques through cross-validation and interpolation were effective in improving model performance. The four parameters included in the model and the cumulative value of the model were available for quality prediction as additional parameters. Among these five parameter candidates, two parameters with linearity were finally identified. The predictive outcomes for firmness, soluble solids content, acidity, and anthocyanin levels in strawberry fruit, based on the two identified parameters, are as follows: The first parameter, ps, demonstrated RMSE performances of 1.0 N, 2.3 %, 0.1 %, and 2.0 mg per 100 g fresh fruit for firmness, soluble solids content, acidity, and anthocyanin, respectively. The second parameter, p3, showed RMSE performances of 0.6 N, 1.2 %, 0.1 %, and 1.8 mg per 100 g fresh fruit, respectively. The proposed non-destructive analysis method shows the potential to overcome the challenges associated with destructive testing methods for assessing certain internal qualities of strawberry fruit.


Assuntos
Fragaria , Frutas , Imageamento Hiperespectral , Fragaria/química , Fragaria/crescimento & desenvolvimento , Frutas/química , Imageamento Hiperespectral/métodos , Antocianinas/análise
12.
J Clin Med ; 13(15)2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39124817

RESUMO

Background: Allergic diseases are common in children and adolescents. It is important to assess the prevalence and risk factors of environmental diseases to implement tailored countermeasures. Methods: This questionnaire study investigated factors associated with environmental diseases in elementary school children with an environmental disease from 150 households in Daejeon Metropolitan City, South Korea in 2021. Results: The participants comprised 55.7% girls and 44.3% boys, and the mean age was 10.1 years with an even age distribution. The typical risk factors observed were the type of roads nearby, the presence of mold or stains within the residence, pet ownership, and frequency of indoor ventilation and cleaning. Notably, 73.2% of the households had an eight-lane road nearby, 40.2% reported leaks, stains, or mold within their homes during the past year, and 37.1% ventilated their homes for less than 30 min. After education on preventing and managing environmental diseases, significant changes were observed in bedding washing frequency, average ventilation duration per session, and duration of humidifier usage (p < 0.05-0.001), with improvements in lifestyle. Conclusions: Our study can be used as a reference for expanding indoor air quality control education for parents with children with an environmental disease and providing tailored environmental consultations.

13.
Medicine (Baltimore) ; 103(32): e39055, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121320

RESUMO

Polycystic ovary syndrome (PCOS) is a disease caused by excessive ovarian androgen secretion due to hypothalamic-pituitary-ovarian hormone abnormalities. We retrospectively investigated the treatment status of patients diagnosed with PCOS who visited a domestic tertiary hospital in order to analyze the use patterns and safety of drugs. Patients diagnosed with PCOS between July 2014 and September 2022 were examined, excluding patients younger than 13 years and those not receiving medication. Patients aged 21 years or younger were designated as the adolescent group and patients aged 22 years or older were designated as the adult group for comparative statistical analysis. The total number of patients was 212, including 105 adolescents (49.5%) and 107 adults (50.5%). Comorbidities were ovarian cyst in 20 (9.4%) patients, endometriosis in 19 (9%), diabetes in 14 (6.6%), thyroid dysfunction in 12 (5.7%), hypertension in 10 (4.7%), dyslipidemia in 10 (4.7%), and androgenic alopecia in 6 (2.8%). Symptoms were oligomenorrhea in 91 (42.9%) patients, amenorrhea in 72 (34%), hirsutism in 36 (17%), acne in 24 (11.3%), and infertility in 10 (4.7%). During the study period, 114 patients (53.8%) were prescribed medroxyprogesterone acetate (MPA), 66 (31.1%) were given oral contraceptives (specifically, ethinyl estradiol + drospirenone prescribed to 52 (24.5%)), and 17 (8%) were concurrently prescribed MPA and oral contraceptives. Forty-five (21.2%) patients changed prescriptions, with 10 (22.2%) switching due to side effects and 8 (17.8%) due to a therapeutic failure. A total of 5 patients (2.4%) discontinued the drug. Adverse drug reactions occurred in 15 patients (7.1%), with 5 being adolescents (4.8%) and 10 being adults (9.3%). MPA alone and ethinyl estradiol with drospirenone were the most prescribed medications for PCOS. Over the study, 45 patients changed prescriptions, 50 were lost to follow-up, and 5 adults discontinued medications.


Assuntos
Síndrome do Ovário Policístico , Centros de Atenção Terciária , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/epidemiologia , Feminino , Estudos Retrospectivos , República da Coreia/epidemiologia , Adulto , Adolescente , Adulto Jovem , Centros de Atenção Terciária/estatística & dados numéricos , Hospitais de Ensino
14.
Int J Mol Sci ; 25(15)2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39125582

RESUMO

Human retinal organoids (ROs) have emerged as valuable tools for studying retinal development, modeling human retinal diseases, and screening drugs. However, their application is limited primarily due to time-intensive generation, high costs, and low reproducibility. Quality assessment of RO differentiation is crucial for their application in research. However, traditional methods such as morphological evaluation and immunohistochemical analysis have limitations due to their lack of precision and invasiveness, respectively. This study aims to identify non-invasive biomarkers for RO differentiation quality using exosomal microRNAs (miRNAs), which are known to reflect cell-specific functions and development in the retina. We differentiated ROs from human induced pluripotent stem cells (hiPSCs) and classified them into 'superior' and 'inferior' groups based on morphological and immunohistochemical criteria. Exosomes from the conditioned media were isolated and analyzed for miRNA content. Our findings revealed distinct miRNA profiles between superior and inferior ROs, with superior ROs exhibiting higher miRNA diversity and specifically up- or down-regulated miRNAs. Gene ontology and pathway enrichment analyses indicated that the target genes of these miRNAs are involved in neuron proliferation and differentiation. The study suggests the potential of exosomal hsa-miR-654-3p and hsa-miR-451a as non-invasive biomarkers for real-time monitoring of RO quality, facilitating the development of standardized, efficient, and cost-effective culture methods.


Assuntos
Biomarcadores , Diferenciação Celular , Exossomos , Células-Tronco Pluripotentes Induzidas , MicroRNAs , Organoides , Retina , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Organoides/metabolismo , Organoides/citologia , Diferenciação Celular/genética , Retina/citologia , Retina/metabolismo , Biomarcadores/metabolismo , Exossomos/metabolismo , Exossomos/genética , Células Cultivadas
15.
Brain Stimul ; 17(5): 1048-1059, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39214184

RESUMO

BACKGROUND AND OBJECTIVES: The effects of noninvasive focused magnetothermal brain stimulation using magnetic nanoparticles (MNPs) on post-stroke motor deficits and metabolic dormancy in subacute ischemic injury are not well-established. This study examined if magnetothermal brain stimulation using magnetic nanoparticles (Nano-MS) enhances motor recovery after stroke. METHODS: We randomly distributed rats into Sham, Control, MNP injection only, and Nano-MS groups. We administered focused magnetic stimulation for 30 min daily following an MNP injection (15 mg/mL) into the targeted motor cortex via the carotid artery three weeks after the transient (90 min) middle cerebral artery occlusion. We assessed motor functionality via behavioral tests and conducted positron emission tomography (PET) imaging to verify cerebral metabolic activity. We assessed neuronal excitability, neuroinflammation, blood-brain barrier (BBB) integrity, and neurogenesis four weeks post-stroke. RESULTS: The Nano-MS group exhibited significantly improved motor deficits and cerebral metabolic activity compared to the Control and MNP groups (p < 0.05). Focused Nano-MS modulated neuronal excitability, evident by a depolarized action potential threshold for spike initiation and reduced firing frequency post-stroke. The Nano-MS group demonstrated markedly decreased inflammatory markers, such as IL-1ß, IL-6, TNF-α, MCP-1, and ICAM-1, compared to the Control and MNP groups. BBB integrity and immunofluorescence for neurogenesis markers were substantially improved in the Nano-MS group. CONCLUSIONS: Focused Nano-MS facilitates the recovery of motor deficits and metabolic inactivity in the brain by effectively modulating excitability, reducing neuroinflammation, enhancing BBB stability, and promoting neurogenesis. Nano-MS is a potential novel, noninvasive therapy for stroke rehabilitation. Further investigation is warranted.

16.
PLoS Pathog ; 20(8): e1012474, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39186780

RESUMO

The bacterium Vibrio vulnificus causes fatal septicemia in humans. Previously, we reported that an extracellular metalloprotease, vEP-45, secreted by V. vulnificus, undergoes self-proteolysis to generate a 34 kDa protease (vEP-34) by losing its C-terminal domain to produce the C-ter100 peptide. Moreover, we revealed that vEP-45 and vEP-34 proteases induce blood coagulation and activate the kallikrein/kinin system. However, the role of the C-ter100 peptide fragment released from vEP-45 in inducing inflammation is still unclear. Here, we elucidate, for the first time, the effects of C-ter100 on inducing inflammation and activating host innate immunity. Our results showed that C-ter100 could activate NF-κB by binding to the receptor TLR4, thereby promoting the secretion of inflammatory cytokines and molecules, such as TNF-α and nitric oxide (NO). Furthermore, C-ter100 could prime and activate the NLRP3 inflammasome (NLRP3, ASC, and caspase 1), causing IL-1ß secretion. In mice, C-ter100 induced the recruitment of immune cells, such as neutrophils and monocytes, along with histamine release into the plasma. Furthermore, the inflammatory response induced by C-ter100 could be effectively neutralized by an anti-C-ter100 monoclonal antibody (C-ter100Mab). These results demonstrate that C-ter100 can be a pathogen-associated molecular pattern (PAMP) that activates an innate immune response during Vibrio infection and could be a target for the development of antibiotics.


Assuntos
Imunidade Inata , Inflamação , Vibrio vulnificus , Animais , Camundongos , Inflamação/imunologia , Inflamação/metabolismo , Vibrio vulnificus/imunologia , Vibrioses/imunologia , Camundongos Endogâmicos C57BL , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/imunologia
17.
J Mater Chem B ; 12(36): 9030-9036, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39158417

RESUMO

Management of diseases through medication accounts for the largest portion of treatment, with people worldwide relying on a variety of medicines to treat and prevent minor to severe diseases in modern society. However, the recent increased use of counterfeit medicines rather than certified medication has emerged as a serious social concern. This study introduces a new hybrid material, named SBBF-chitosan (SC), which integrates a single-benzene-based fluorophore (SBBF) and chitosan, serving as a fluorescence-based authentication barcode for certified medication. The synthesis and characterization of SC, along with an analysis of its photophysical properties, were systematically conducted. SC demonstrated bright emission with high stability under various environmental conditions. In vitro analyses and in vivo animal experiment results further indicated the safety of SC for oral intake, even when directly incorporated into medicines. We are confident that this newly developed formulation SC provides a fundamental solution to address the challenges posed by counterfeit medicines, thereby safeguarding medication authenticity.


Assuntos
Quitosana , Corantes Fluorescentes , Quitosana/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Animais , Camundongos , Humanos
18.
J Vasc Surg Venous Lymphat Disord ; : 101964, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39209025

RESUMO

OBJECTIVE: Hand arteriovenous malformations (AVMs) are extremely difficult to manage for their functional importance and cosmetic disfiguration. A single-center retrospective study was conducted to identify long-term outcomes of multidisciplinary team management of hand AVMs. METHODS: Institutional review board approved this retrospective study. Multidisciplinary vascular anomalies center data was reviewed from 1995 to 2023. Patient demographics, Schobinger's AVM stage, sclerotherapy details, surgical history, and adverse events after sclerotherapy were reviewed. RESULTS: A total of 150 patients with hand AVMs visited our hospital from 1995 to 2023, with a mean age of 33 years (range, 1-75 years), and 91 were females. Forty-four patients were Schobinger stage II, and 106 were stage III. Sclerotherapy was performed on 101 patients (67%) with 320 sessions. Angiographic devascularization rates after sclerotherapy were: 16 with 100%, 30 with over 90%, 34 with 50% to 90%, 15 with 0% to 50%, and six showed aggravation. Sclerotherapy-related adverse events occurred in 123 of 320 sessions (39%), with 112 minor and 11 major events. Fifteen patients (15%) eventually underwent amputation surgery a mean of 1618 days after sclerotherapy for necrosis (n = 3) and delayed complications (n = 12). Thirteen patients (9%) underwent primary surgical amputation for ulcers or bleeding (all Schobinger stage III). Thirty-six patients (24%) were followed without any procedure. CONCLUSIONS: Multidisciplinary management of hand AVMs shows varied long-term outcomes. Although sclerotherapy is effective for many patients, it carries a significant risk of adverse events. The necessity for amputation in some cases highlights the severity of advanced AVMs and the need for individualized treatment approaches.

19.
Microorganisms ; 12(8)2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39203488

RESUMO

Given the lack of genetic characterization data for multidrug-resistant (MDR) Salmonella in South Korean poultry, we analyzed 53 MDR Salmonella strains from 1232 poultry meat samples (723 chicken, 509 duck) using whole-genome sequencing. Five serotypes were identified: S. Infantis (30/53, 56.6%), S. Enteritidis (11/53, 20.8%), S. Virchow (9/53, 17.0%), S. Agona (2/53, 3.8%), and S. Indiana (1/53, 1.9%). Sequence types (STs) included ST32, ST11, ST16, ST13, and ST17, with three major clusters, each having two subclusters. Eight core genome sequence types (cgSTs) were identified: 225993, 2268, 58360, 150996, 232041, 96964, 117577, and 267045. Salmonella Infantis and S. Enteritidis had two (117577, 267045) and three (225993, 2268, 58360) cgSTs, respectively, whereas S. Virchow showed allelic differences in identical cgSTs. The S. Enteritidis subcluster was classified as chicken or duck. Twenty-eight antimicrobial resistance genes (ARGs), 10 plasmid replicons, 11 Salmonella pathogenicity islands (SPIs), and 230 virulence genes were identified, showing distinct profiles by cluster and subcluster. Salmonella Infantis, the primary MDR Salmonella, carried the IncFIB (pN55391) plasmid, 10-11 ARGs, nine SPIs, and approximately 163 virulence genes. Three major MDR Salmonella serotypes (S. Infantis, S. Enteritidis, and S. Virchow) had specific genetic profiles that can inform epidemiological surveillance.

20.
Front Vet Sci ; 11: 1448249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39205804

RESUMO

Background: The grade of tracheal collapse (TC) is assessed by the diameter of the narrowed lumen. However, studies on the relationship between TC grade and clinical symptom severity are lacking. Objectives: To investigate the clinical characteristics of small-breed dogs diagnosed with TC and determine if fluoroscopic grading correlates with cough severity. Methods: We retrospectively reviewed medical records from 2022 to 2024. TC diagnosis was confirmed using fluoroscopic examination. Multiple linear regression was employed to investigate factors influencing cough severity, with a significance level set at p < 0.05. Results: A total of 132 dogs with TC were identified, of which 22 were excluded. The final cohort consisted of 110 dogs, aged between 2-19 years, with no significant sex differences. The majority (97.2%) of dogs had a BCS of ≥4. Among the top four breeds (Maltese, Pomeranian, Poodle, and Chihuahua), the most severe collapse was observed in the carinal region. The grade of collapse on fluoroscopy was mostly related to high BCS (p < 0.007) and low body weight (p < 0.001). However, interestingly, fluoroscopic findings of collapse location and grade did not correlate with cough severity (p = 0.350). Notably, clinical symptoms improved in 86.6% of cases following interventions such as weight reduction, environmental changes, and pharmacotherapy. Conclusions and clinical relevance: In small-breed dogs, the severity of cough was not associated with the region or grade of TC diagnosed by fluoroscopy.

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