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1.
Front Endocrinol (Lausanne) ; 15: 1420024, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280007

RESUMEN

Introduction: Bruton's tyrosine kinase (BTK) and interleukin (IL)-2 Inducible T-cell Kinase (ITK) inhibitors have anti-inflammatory properties. We investigated the therapeutic effect of ibrutinib, an orally bioavailable BTK/ITK inhibitor, in a mouse model of Graves' orbitopathy (GO). Methods: Genetic immunization was performed through intramuscular administration of the recombinant plasmid, pCMV6-hTSHR cDNA, to 8-week-old female BALB/c mice. Serum levels of T3, T4, and thyroid-stimulating hormone receptor (TSHR) antibodies (TRAbs) were quantified using enzyme-linked immunosorbent assay. Histopathological changes in orbital tissues were examined using immunohistochemistry (IHC) staining for TSHR and various inflammatory markers. Following successful genetic immunization, ibrutinib was orally administered daily for 2 weeks in the GO model mice. After treatment, the mRNA and protein expression levels of BTK, ITK, IL-1ß, and IL-6 in orbital tissues were evaluated using real-time PCR and Western blotting. Results: In total, 20 mice were sacrificed to confirm successful genetic immunization. The GO mouse group exhibited significantly increased serum T3, T4, and TRAb levels. IHC revealed increased expression of TSHR, IL-1ß, IL-6, transforming growth factor-ß1, interferon-γ, CD40, CD4, BTK, and ITK in the GO mouse model. The orbital inflammation was significantly attenuated in ibrutinib-treated mice. The mRNA and protein expression levels of BTK, ITK, IL-1ß, and IL-6 in orbital tissue were lower in ibrutinib-treated GO mouse group compared to the phosphate-buffered saline-treated GO mouse group. Conclusion: The GO mouse model demonstrated enhanced BTK and ITK expression. Ibrutinib, a BTK/ITK inhibitor, suppressed the inflammatory cytokine production. These findings highlight the potential involvement of BTK/ITK in the inflammatory pathogenesis of GO, suggesting its role as a novel therapeutic target.


Asunto(s)
Adenina , Agammaglobulinemia Tirosina Quinasa , Modelos Animales de Enfermedad , Oftalmopatía de Graves , Inflamación , Ratones Endogámicos BALB C , Piperidinas , Pirimidinas , Animales , Oftalmopatía de Graves/tratamiento farmacológico , Oftalmopatía de Graves/metabolismo , Oftalmopatía de Graves/patología , Adenina/análogos & derivados , Piperidinas/uso terapéutico , Ratones , Femenino , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Agammaglobulinemia Tirosina Quinasa/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/patología , Pirimidinas/uso terapéutico , Pirazoles/uso terapéutico , Pirazoles/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/metabolismo , Receptores de Tirotropina/metabolismo , Receptores de Tirotropina/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico
2.
Cancer Res Treat ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39265620

RESUMEN

Purpose: Major pathologic response (MPR), defined as ≤10% of residual viable tumor (VT), is a prognostic factor in non-small cell lung cancer (NSCLC) after neoadjuvant therapy. This study evaluated interobserver reproducibility in assessing MPR, compared area-weighted and unweighted VT (%) calculation, and determined optimal VT (%) cutoffs across histologic subtypes for survival prediction. Materials and Methods: This retrospective study included 108 patients with NSCLC who underwent surgical resection after neoadjuvant chemotherapy or chemoradiation at Seoul National University Bundang Hospital between 2009-2018. Three observers with varying expertise independently assessed tumor bed and VT (%) based on digital whole-slide images. Results: Reproducibility in tumor bed delineation was reduced in squamous cell carcinoma (SqCC) with smaller tumor bed, although overall concordance was high (Dice coefficient, 0.96; IoU score, 0.92). Excellent agreement was achieved for VT (%) (ICC=0.959) and MPR using 10% cutoff (Fleiss' kappa=0.911). Shifting between area-weighted and unweighted VT (%) showed only one case differing in MPR status out of 81 cases. The optimal cutoff was 10% for both adenocarcinoma (ADC) and SqCC. MPR+ was observed in 18 patients (17%), with SqCC showing higher MPR+ rates (p=0.044), lower VT (%) (p<0.001), and better event-free survival (p=0.015) than ADC. MPR+ significantly improved overall survival (p=0.023), event-free survival (p=0.001), and lung cancer-specific survival (p=0.012). Conclusion: While MPR assessment demonstrated robust reproducibility with minimal impact from the tumor bed, attention is warranted when evaluating smaller tumor beds in SqCC. A 10% cutoff reliably predicted survival across histologic subtypes with higher interobserver reproducibility.

3.
J Biomed Inform ; 157: 104720, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39233209

RESUMEN

BACKGROUND: In oncology, electronic health records contain textual key information for the diagnosis, staging, and treatment planning of patients with cancer. However, text data processing requires a lot of time and effort, which limits the utilization of these data. Recent advances in natural language processing (NLP) technology, including large language models, can be applied to cancer research. Particularly, extracting the information required for the pathological stage from surgical pathology reports can be utilized to update cancer staging according to the latest cancer staging guidelines. OBJECTIVES: This study has two main objectives. The first objective is to evaluate the performance of extracting information from text-based surgical pathology reports and determining pathological stages based on the extracted information using fine-tuned generative language models (GLMs) for patients with lung cancer. The second objective is to determine the feasibility of utilizing relatively small GLMs for information extraction in a resource-constrained computing environment. METHODS: Lung cancer surgical pathology reports were collected from the Common Data Model database of Seoul National University Bundang Hospital (SNUBH), a tertiary hospital in Korea. We selected 42 descriptors necessary for tumor-node (TN) classification based on these reports and created a gold standard with validation by two clinical experts. The pathology reports and gold standard were used to generate prompt-response pairs for training and evaluating GLMs which then were used to extract information required for staging from pathology reports. RESULTS: We evaluated the information extraction performance of six trained models as well as their performance in TN classification using the extracted information. The Deductive Mistral-7B model, which was pre-trained with the deductive dataset, showed the best performance overall, with an exact match ratio of 92.24% in the information extraction problem and an accuracy of 0.9876 (predicting T and N classification concurrently) in classification. CONCLUSION: This study demonstrated that training GLMs with deductive datasets can improve information extraction performance, and GLMs with a relatively small number of parameters at approximately seven billion can achieve high performance in this problem. The proposed GLM-based information extraction method is expected to be useful in clinical decision-making support, lung cancer staging and research.


Asunto(s)
Neoplasias Pulmonares , Procesamiento de Lenguaje Natural , Estadificación de Neoplasias , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/diagnóstico , Humanos , Estadificación de Neoplasias/métodos , Registros Electrónicos de Salud , Minería de Datos/métodos , Algoritmos , Bases de Datos Factuales
4.
Korean J Radiol ; 25(8): 715-725, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39109500

RESUMEN

OBJECTIVE: To evaluate the outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) according to the size of the beads for the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 212 patients with a single HCC ≤5 cm from five tertiary institutions. One hundred and nine patients were treated with 70-150-µm doxorubicin DEBs (group A), and 103 patients received 100-300-µm doxorubicin DEBs (group B). The initial tumor response (assessed between 3 weeks and 2 months after DEB-TACE), time to local tumor progression (TTLTP), restricted mean duration of complete response (RMDCR), rate of complications, incidence of post-embolization syndrome, and length of hospital stay were compared between the two groups. Logistic regression was used to analyze prognostic factors for initial tumor response. RESULTS: The initial objective response rates were 91.7% (100/109) and 84.5% (87/103) for groups A and B, respectively (P = 0.101). In the subgroup analysis of tumors ≤3 cm, the initial objective response rates were 94.6% (53/56) and 78.0% (39/50) for groups A and B, respectively (P = 0.012). There was no significant difference in the TTLTP (median, 23.7 months for group A vs. 19.0 months for group B; P = 0.278 [log-rank], 0.190 [multivariable Cox regression]) or RMDCR at 24 months (11.4 months vs. 8.5 months, respectively; P = 0.088). In the subgroup analysis of tumors >3-cm, the RMDCR at 24 months was significantly longer in group A than in group B (11.8 months vs. 5.7 months, P = 0.024). The incidence of mild bile duct dilatation after DEB-TACE was significantly higher in group B than in group A (5.5% [6/109] vs. 18.4% [19/103], P = 0.003). CONCLUSION: DEB-TACE using 70-150-µm microspheres demonstrated a higher initial objective response rate in ≤3-cm HCCs and a longer RMDCR at 24 months in 3.1-5-cm HCCs compared to larger DEBs (100-300-µm).


Asunto(s)
Antibióticos Antineoplásicos , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Doxorrubicina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico por imagen , Quimioembolización Terapéutica/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Doxorrubicina/administración & dosificación , Resultado del Tratamiento , República de Corea , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Microesferas , Adulto
5.
J Invest Dermatol ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39122145

RESUMEN

Numerous recent evidence highlights epidemiological connections between rosacea and metabolic disorders. However, the precise path through which metabolic factors impact rosacea risk is still unclear. Therefore, this study aims to investigate the role of adiponectin, a crucial adipokine that regulates metabolic homeostasis, in the pathogenesis of rosacea. We elucidated a detrimental feedback loop between rosacea-like skin inflammation and decreased levels of skin adiponectin. To elaborate, rosacea lesional skin exhibits diminished adiponectin expression compared with nonlesional areas in the same patients. Induction of rosacea-like inflammation reduced adiponectin levels in the skin by generating inflammatory cytokines that suppress adiponectin production from subcutaneous adipocytes. Conversely, complete depletion of adiponectin exacerbated rosacea-like features in the mouse model. Mechanistically, adiponectin deficiency led to heightened S6 phosphorylation, a marker of the mTORC1 signaling pathway, in the epidermis. Adiponectin significantly inhibited S6 phosphorylation in cultured keratinocytes. Notably, replenishing adiponectin whole protein or topically applying an agonist for adiponectin receptor 1 successfully improved rosacea-like features in mice. This study contributes to understanding the role of adiponectin in skin inflammation associated with rosacea pathophysiology, suggesting that restoring adiponectin function in the skin could be a potential therapeutic strategy.

7.
Front Vet Sci ; 11: 1411886, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011319

RESUMEN

Acute lung injury is an acute inflammation disorder that disrupts the lung endothelial and epithelial barriers. In this study, we investigated the extracellular vesicles (EVs) obtained via priming inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ on canine adipose mesenchymal stem cells in improving their anti-inflammatory and/or immunosuppressive potential, and/or their ability to alleviate lipopolysaccharide-induced lung injury in vitro. We also explored the correlation between epithelial-to-mesenchymal transition and the inflammatory repressive effect of primed EVs. Using small RNA-Seq, we confirmed that miR-16 and miR-502 significantly increased in EVs from TNF-α and IFN-γ-primed canine adipose mesenchymal stem cells. The pro and anti-inflammatory cytokines were analyzed in a lipopolysaccharide-induced lung injury model and we found that the EV anti-inflammatory effect improved on priming with inflammatory cytokines. EVs obtained from primed stem cells effectively suppress endothelial-to-mesenchymal transition in a lung injury model. Our results suggest a potential therapeutic approach utilizing EVs obtained from adipose mesenchymal stem cells primed with TNF-α and IFN-γ against lung inflammation and endothelial to mesenchymal transition.

8.
Sci Rep ; 14(1): 17175, 2024 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060447

RESUMEN

This study aimed to determine whether urinary creatinine excretion rate (CER), a marker of muscle mass, is associated with diabetic retinopathy in individuals with type 2 diabetes and to ascertain whether this putative association depends on body mass index (BMI). This cross sectional study evaluated 2035 individuals with type 2 diabetes. Twenty-four-hour urine was collected. Individuals with diabetic retinopathy had lower CER and BMI values than those without. Patients in higher CER quartiles had higher BMI values and a lower prevalence of diabetic retinopathy. A significant relationship between CER and diabetic retinopathy persisted, even after adjusting for traditional risk factors, including glycated hemoglobin, diabetes duration, and hypertension, in multivariable analysis. Further adjustment for BMI did not significantly alter the association between CER and diabetic retinopathy. This study suggests that CER is inversely associated with diabetic retinopathy in individuals with type 2 diabetes, and this association is independent of BMI.


Asunto(s)
Índice de Masa Corporal , Creatinina , Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Humanos , Diabetes Mellitus Tipo 2/orina , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/orina , Retinopatía Diabética/etiología , Masculino , Femenino , Persona de Mediana Edad , Creatinina/orina , Estudios Transversales , Anciano , Factores de Riesgo , Biomarcadores/orina
9.
Radiographics ; 44(8): e230140, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38990775

RESUMEN

Ectopic varices are rare but potentially life-threatening conditions usually resulting from a combination of global portal hypertension and local occlusive components. As imaging, innovative devices, and interventional radiologic techniques evolve and are more widely adopted, interventional radiology is becoming essential in the management of ectopic varices. The interventional radiologist starts by diagnosing the underlying causes of portal hypertension and evaluating the afferent and efferent veins of ectopic varices with CT. If decompensated portal hypertension is causing ectopic varices, placement of a transjugular intrahepatic portosystemic shunt is considered the first-line treatment, although this treatment alone may not be effective in managing ectopic variceal bleeding because it may not sufficiently resolve focal mesenteric venous obstruction causing ectopic varices. Therefore, additional variceal embolization should be considered after placement of a transjugular intrahepatic portosystemic shunt. Retrograde transvenous obliteration can serve as a definitive treatment when the efferent vein connected to the systemic vein is accessible. Antegrade transvenous obliteration is a vital component of interventional radiologic management of ectopic varices because ectopic varices often exhibit complex anatomy and commonly lack catheterizable portosystemic shunts. Superficial veins of the portal venous system such as recanalized umbilical veins may provide safe access for antegrade transvenous obliteration. Given the absence of consensus and guidelines, a multidisciplinary team approach is essential for the individualized management of ectopic varices. Interventional radiologists must be knowledgeable about the anatomy and hemodynamic characteristics of ectopic varices based on CT images and be prepared to consider appropriate options for each specific situation. ©RSNA, 2024 Supplemental material is available for this article.


Asunto(s)
Hemorragia Gastrointestinal , Derivación Portosistémica Intrahepática Transyugular , Humanos , Derivación Portosistémica Intrahepática Transyugular/métodos , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/etiología , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/terapia , Hipertensión Portal/diagnóstico por imagen , Hipertensión Portal/complicaciones , Várices/diagnóstico por imagen , Várices/terapia , Radiografía Intervencional/métodos , Radiología Intervencionista/métodos , Embolización Terapéutica/métodos , Tomografía Computarizada por Rayos X/métodos
10.
J Vet Sci ; 25(3): e37, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38834507

RESUMEN

IMPORTANCE: The portal vein to aorta (PV/Ao) ratio is used to assess the clinical significance of extrahepatic portosystemic shunt (EHPSS). Previous studies using computed tomography (CT) were conducted in dogs but not in cats. OBJECTIVE: This study aimed to establish normal reference values for PV indices (PV/Ao ratio and PV diameter) in cats and determine the usefulness of these for predicting symptomatic EHPSS. METHODS: This study included 95 dogs and 114 cats that underwent abdominal CT. The canine normal (CN) group included dogs without EHPSS. The cats were classified into feline normal (FN, 88/114), feline asymptomatic (FA, 16/114), and feline symptomatic (FS, 10/114) groups. The PV and Ao diameters were measured in axial cross-sections. RESULTS: The group FN had a higher PV/Ao ratio than the group CN (p < 0.001). Within the feline groups, the PV indices were in the order FN > FA > FS (both p < 0.001). The mean PV diameter and PV/Ao ratio for group FN were 5.23 ± 0.77 mm and 1.46 ± 0.19, respectively. The cutoff values between groups FN and FS were 4.115 mm for PV diameter (sensitivity, 100%; specificity, 97.7%) and 1.170 for PV/Ao ratio (90%, 92.1%). The cutoff values between group FA and FS were 3.835 mm (90%, 93.8%) and 1.010 (70%, 100%), respectively. CONCLUSIONS AND RELEVANCE: The results demonstrated significant differences in PV indices between dogs and cats. In cats, the PV/Ao ratio demonstrated high diagnostic performance for symptomatic EHPSS. The PV diameter also performed well, in contrast to dogs.


Asunto(s)
Enfermedades de los Gatos , Vena Porta , Tomografía Computarizada por Rayos X , Animales , Gatos , Vena Porta/diagnóstico por imagen , Vena Porta/anomalías , Enfermedades de los Gatos/diagnóstico por imagen , Masculino , Femenino , Tomografía Computarizada por Rayos X/veterinaria , Perros , Enfermedades de los Perros/diagnóstico por imagen , Valores de Referencia , Aorta/diagnóstico por imagen
11.
Front Immunol ; 15: 1365430, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38840912

RESUMEN

The presence of the blood group H2 antigen on the membrane of red blood cells determines blood type O in individuals and this H2 antigen serves as a precursor to the A and B antigens expressed in blood types A and B, respectively. However, the specific involvement of ABH antigens in skin diseases is unknown. Therefore, we aim to investigate the expression of ABH antigens in skin tissue of patients with atopic dermatitis (AD) and MC903-induced AD-like mice. We demonstrated that the expression of ABH antigen is primarily located in the granular and horny layers of the skin in healthy control individuals. However, in patients with AD, the expression of the ABH antigen was absent or diminished in these layers, while the H2 antigen expression increased in the spinous layers of the affected skin lesions. Then, we investigated the biological function of blood group H antigen mediated by fucosyltransferase 1 (Fut1) in the skin, utilizing an AD mouse model induced by MC903 in wild-type (WT) and Fut1-knockout mice. After the application of MC903, Fut1-deficient mice, with no H2 antigen expression on their skin, exhibited more severe clinical signs, increased ear swelling, and elevated serum IgE levels compared with those of WT mice. Additionally, the MC903-induced thickening of both the epidermis and dermis was more pronounced in Fut1-deficient mice than that in WT mice. Furthermore, Fut1-deficient mice showed a significantly higher production of interleukin-4 (IL-4) and IL-6 in skin lesions compared with that of their WT counterparts. The expression of chemokines, particularly Ccl2 and Ccl8, was notably higher in Fut1-deficient mice compared with those of WT mice. The infiltration of CD4+ T cells, eosinophils, and mast cells into the lesional skin was significantly elevated in Fut1-deficient mice compared with that in WT mice. These findings demonstrate the protective role of H2 antigen expression against AD-like inflammation and highlight its potential therapeutic impact on AD through the regulation of blood group antigens.


Asunto(s)
Dermatitis Atópica , Fucosiltransferasas , Galactósido 2-alfa-L-Fucosiltransferasa , Ratones Noqueados , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Citocinas/metabolismo , Dermatitis Atópica/inmunología , Modelos Animales de Enfermedad , Epidermis/inmunología , Epidermis/patología , Epidermis/metabolismo , Fucosiltransferasas/genética , Fucosiltransferasas/metabolismo , Ratones Endogámicos C57BL
12.
BMB Rep ; 57(6): 305-310, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38835117

RESUMEN

T-plastin (PLST), a member of the actin-bundling protein family, plays crucial roles in cytoskeletal structure, regulation, and motility. Studies have shown that the plastin family is associated with the malignant characteristics of cancer, such as circulating tumor cells and metastasis, by inducing epithelialmesenchymal transition (EMT) in various cancer cells. However, the role of PLST in the EMT of human lung cancer cells remains unclear. In this study, we observed that PLST overexpression enhanced cell migratory and invasive abilities, whereas its downregulation resulted in their suppression. Moreover, PLST expression levels were associated with the expression patterns of EMT markers, including E-cadherin, vimentin, and Slug. Furthermore, the phosphorylation levels of focal adhesion kinase (FAK) and AKT serine/threonine kinase (AKT) were dependent on PLST expression levels. These findings indicate that PLST induces the migration and invasion of human lung cancer cells by promoting Slug-mediated EMT via the FAK/AKT signaling pathway. [BMB Reports 2024; 57(6): 305-310].


Asunto(s)
Movimiento Celular , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares , Proteínas de Microfilamentos , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Factores de Transcripción de la Familia Snail , Humanos , Cadherinas/metabolismo , Línea Celular Tumoral , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/genética , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de Microfilamentos/metabolismo , Invasividad Neoplásica , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo
13.
Pathogens ; 13(6)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38921772

RESUMEN

(1) Background: Peptides are appealing as pharmacological materials because they are easily produced, safe, and tolerable. Despite increasing gum-care awareness, periodontitis is still prevalent and is influenced by factors like high sugar consumption, smoking, and aging. Porphyromonas gingivalis is considered a major etiologic agent of periodontitis and activates the NLR family pyrin domain containing 3 (NLRP3) but is absent in melanoma 2 (AIM2) inflammasomes, resulting in pro-inflammatory cytokine release. (2) Methods: We examined the anti-inflammatory effects of 18 peptides derived from human stromal cell-derived factor-1 (SDF-1) on THP-1 macrophages. Inflammation was induced by P. gingivalis, and the anti-inflammatory effects were analyzed using molecular biological techniques. In a mouse periodontitis model, alveolar bone resorption was assessed using micro-CT. (3) Results: Of the 18 SDF-1-derived peptides, S10 notably reduced IL-1ß and TNF-α secretion. S10 also diminished the P. gingivalis-induced expression of NLRP3, AIM2, ASC (apoptosis-associated speck-like protein), caspase-1, and IL-1ß. Furthermore, S10 attenuated the enhanced TLR (toll-like receptor) signaling pathway and decreased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). In addition, S10 mitigated alveolar bone loss in our P. gingivalis-induced mouse model of periodontitis. (4) Conclusions: S10 suppressed TLR/NF-κB/NLRP3 inflammasome signaling and the AIM2 inflammasome in our P. gingivalis-induced murine periodontitis model, which suggests that it has potential use as a therapeutic treatment for periodontitis.

14.
Exp Mol Med ; 56(6): 1401-1411, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38825641

RESUMEN

The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure.


Asunto(s)
Dopamina , Trastornos de la Memoria , Rayos Ultravioleta , Animales , Dopamina/metabolismo , Rayos Ultravioleta/efectos adversos , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Ratones , Masculino , Neurogénesis/efectos de la radiación , Plasticidad Neuronal/efectos de la radiación , Hipocampo/metabolismo , Hipocampo/efectos de la radiación , Piel/metabolismo , Piel/efectos de la radiación , Transducción de Señal , Ratones Endogámicos C57BL , Receptores de Dopamina D1/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/efectos de la radiación
15.
Sci Rep ; 14(1): 14286, 2024 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-38902320

RESUMEN

The mechanism and predictive biomarkers of sinonasal inverted papilloma (IP) transformation into squamous cell carcinoma (SCC) are still unclear. We investigated the genetic mutations involved and the predictive biomarkers. Fourteen patients with SCC arising from IP and six patients with IPs without malignant transformation (sIP) were included. DNA was extracted separately from areas of normal tissue, IP, dysplasia, and SCC. Whole exome sequencing and immunohistochemistry was performed. Major oncogenic mutations were observed in the progression from IP to SCC. The most frequently mutated genes were TP53 (39%) and CDKN2A (27%). Mutations in TP53 and/or CDKN2A were observed in three of six IPs with malignant transformation (cIP); none were observed in sIPs. Tumor mutational burden (TMB) increased from IP to SCC (0.64/Mb, 1.11/Mb, and 1.25 for IP, dysplasia, and SCC, respectively). TMB was higher in the cIPs than in the sIPs (0.64/Mb vs 0.3/Mb). Three cIPs showed a diffuse strong or null pattern in p53, and one showed a total loss of p16, a distinct pattern from sIPs. Our result suggests that TP53 and CDKN2A status can be predictive markers of malignant transformation of IP. Furthermore, immunohistochemistry of p53 and p16 expression can be surrogate markers for TP53 and CDKN2A status.


Asunto(s)
Biomarcadores de Tumor , Transformación Celular Neoplásica , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Papiloma Invertido , Proteína p53 Supresora de Tumor , Humanos , Papiloma Invertido/genética , Papiloma Invertido/patología , Papiloma Invertido/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Masculino , Femenino , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Anciano , Neoplasias de los Senos Paranasales/genética , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/metabolismo , Mutación , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Adulto , Anciano de 80 o más Años , Secuenciación del Exoma , Inmunohistoquímica
16.
J Matern Fetal Neonatal Med ; 37(1): 2355495, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38880661

RESUMEN

OBJECTIVES: To determine the effects of cerclage on twin pregnancies. METHODS: A multicenter, retrospective, cohort study was conducted at 10 tertiary centers using a web-based data collection platform. The study population included twin pregnancies delivered after 20 weeks of gestation. Patients with one or two fetal deaths before 20 weeks of gestation were excluded. Maternal characteristics, including prenatal cervical length (CL) and obstetric outcomes, were retrieved from the electronic medical records. RESULTS: A total of 1,473 patients had available data regarding the CL measured before 24 weeks of gestation. Seven patients without CL data obtained prior to cerclage were excluded from the analysis. The study population was divided into two groups according to the CL measured during the mid-trimester: the CL ≤2.5 cm group (n = 127) and the CL >2.5 cm group (n = 1,339). A total of 127 patients (8.7%) were included in the CL ≤2.5 cm group, including 41.7% (53/127) who received cerclage. Patients in the CL >2.5 cm group who received cerclage had significantly lower gestational age at delivery than the control group (hazard ratio (HR): 1.8; 95% confidence interval (CI): 1.11-2.87; p = .016). Patients in the CL ≤2.5 cm group who received cerclage had a significantly higher gestational age at delivery than the control group (HR: 0.5; 95% CI: 0.30-0.82; p value = .006). CONCLUSIONS: In twin pregnancies with a CL ≤2.5 cm, cerclage significantly prolongs gestation. However, unnecessary cerclage in women with a CL >2.5 cm may result in a higher risk of preterm labor and histologic chorioamnionitis although this study has a limitation originated from retrospective design.


Asunto(s)
Cerclaje Cervical , Resultado del Embarazo , Embarazo Gemelar , Humanos , Femenino , Embarazo , Cerclaje Cervical/estadística & datos numéricos , Cerclaje Cervical/métodos , Estudios Retrospectivos , Embarazo Gemelar/estadística & datos numéricos , Adulto , Resultado del Embarazo/epidemiología , Medición de Longitud Cervical , Nacimiento Prematuro/prevención & control , Nacimiento Prematuro/epidemiología , Edad Gestacional , Incompetencia del Cuello del Útero/cirugía
17.
Abdom Radiol (NY) ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38831076

RESUMEN

PURPOSE: To provide detailed reports on radiation doses during transarterial chemoembolization (TACE) in the cone-beam computed tomography (CBCT) era and to identify the associated factors. METHODS: This retrospective study included 385 consecutive patients who underwent initial conventional TACE for hepatocellular carcinoma (HCC) between January 2016 and December 2017. In most cases, CBCT was performed at the common hepatic artery or celiac axis to confirm the location of the tumor and the three-dimensional hepatic artery anatomy. Superselective TACE was performed for all technically feasible cases. Information on total dose area product (DAP), total cumulative air kerma (CAK), fluoroscopy time, and DAP and CAK of each digital subtraction angiography (DSA) and CBCT scan was recorded. Multiple linear regression analysis was performed to identify the factors associated with increased DAP during TACE. RESULTS: The mean values of total DAP and CAK were 165.2 ± 81.2 (Gy·cm²) and 837.1 ± 571.0 (mGy), respectively. The mean fluoroscopy time was 19.1 ± 10.3 min. The mean DAP caused by fluoroscopy, DSA, and CBCT was 51.8 ± 43.9, 28.0 ± 24.1, and 83.9 ± 42.1 Gy·cm², respectively. Male sex, a high body mass index, largest tumor size > 3 cm, presence of aberrant right and left hepatic arteries, and superselective TACE were identified as independent predictors of increased total DAP during TACE. CONCLUSION: We were able to provide detailed reports on radiation doses during TACE and associated factors.

18.
Medicine (Baltimore) ; 103(18): e37988, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701243

RESUMEN

INTRODUCTION: Maternal epilepsy is a critical condition that can significantly affect mothers and fetuses. Notably, the admission of a laboring mother with uncontrolled refractory status epilepticus (RSE) to the operating room presents a challenging scenario for anesthesiologists. THE MAIN SYMPTOMS OF THE PATIENT AND THE IMPORTANT CLINICAL FINDINGS: A 30-year-old primigravida was transferred to the operating room for an emergency cesarean section. Cesarean section was performed after a provisional diagnosis of preeclampsia was made. THE MAIN DIAGNOSES, THERAPEUTIC INTERVENTIONS, AND OUTCOMES: Cesarean section was performed under general anesthesia. During the postoperative period, the patient exhibited no seizure activity in the brain; however, she experienced mild cognitive dysfunction for up to 6 months postdelivery. The neonate were discharged without any complications. CONCLUSION: Inducing anesthesia in pregnant women with ongoing seizure activity are challenging; however, anesthesiologists provide judgment based on the balance between the safety of the mother and fetus and the balance between patient monitoring and the progression of anesthesia. This challenge can be addressed through multidisciplinary collaboration.


Asunto(s)
Anestesia General , Cesárea , Estado Epiléptico , Humanos , Femenino , Cesárea/efectos adversos , Adulto , Estado Epiléptico/etiología , Embarazo , Anestesia General/métodos , Anestesia General/efectos adversos , Complicaciones del Embarazo/cirugía , Anestesia Obstétrica/métodos
19.
Breast Cancer Res Treat ; 206(1): 31-44, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38743175

RESUMEN

PURPOSE: This single-center, randomized, prospective, exploratory clinical trial was conducted to assess the clinical efficacy of an augmented reality (AR)-based breast cancer localization imaging solution for patients with breast cancer. METHODS: This clinical trial enrolled 20 women who were diagnosed with invasive breast cancer between the ages of 19 and 80, had a single lesion with a diameter ≥ 5 mm but ≤ 30 mm, had no metastases to other organs, and had not received prior chemotherapy. All patients underwent mammography, ultrasound, computed tomography, and magnetic resonance imaging for preoperative assessment. Patients were randomly assigned to ultrasound-guided skin marking localization (USL) and AR-based localization (ARL) groups (n = 10 in each group). Statistical comparisons between USL and ARL groups were made based on demographics, radiologic features, pathological outcomes, and surgical outcomes using chi-square and Student t-tests. RESULTS: Two surgeons performed breast-conserving surgery on 20 patients. Histopathologic evaluation of all patients confirmed negative margins. Two independent pathologists evaluated the marginal distances, and there were no intergroup differences in the readers' estimates (R1, 6.20 ± 4.37 vs. 5.04 ± 3.47, P = 0.519; R2, 5.10 ± 4.31 vs. 4.10 ± 2.38, P = 0.970) or the readers' average values (5.65 ± 4.19 vs. 4.57 ± 2.84, P = 0.509). In comparing the tumor plane area ratio, there was no statistically significant difference between the two groups in terms of either reader's mean values (R1, 15.90 ± 9.52 vs. 19.38 ± 14.05, P = 0.525; R2, 15.32 ± 9.48 vs. 20.83 ± 12.85, P = 0.290) or the overall mean values of two readers combined (15.56 ± 9.11 vs. 20.09 ± 13.38, P = 0.388). Convenience, safety, satisfaction, and reusability were all superior in the AR localization group (P < 0.001) based on the two surgeons' responses. CONCLUSION: AR localization is an acceptable alternative to ultrasound-guided skin marking with no significant differences in surgical outcomes.


Asunto(s)
Realidad Aumentada , Neoplasias de la Mama , Mastectomía Segmentaria , Humanos , Femenino , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Persona de Mediana Edad , Mastectomía Segmentaria/métodos , Adulto , Anciano , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Mamografía/métodos , Anciano de 80 o más Años , Adulto Joven , Imagen por Resonancia Magnética/métodos , Resultado del Tratamiento
20.
J Invest Dermatol ; 144(10): 2273-2284.e5, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38775766

RESUMEN

UV irradiation of the human skin downregulates lipid synthesis and adipokine production in subcutaneous fat. Recent evidence has suggested that UV exposure limits body weight gain in mouse models of obesity. However, the relationship between norepinephrine and UV irradiation has not been previously reported. Chronic UV exposure stimulated food intake but prevented body weight gain. Leptin, an appetite-suppressing hormone, was significantly reduced in the serum of the UV-irradiated mice. In contrast, UV irradiation induced browning of subcutaneous white adipose tissues without increasing physical activity. Notably, UV irradiation significantly increased norepinephrine levels, and the inhibition of norepinephrine production reversed the effects of chronic UV irradiation on food intake and body weight gain. In conclusion, chronic UV irradiation induces norepinephrine release, resulting in the stimulation of food intake due to the downregulation of leptin levels, but it prevents weight gain by inducing the browning process and elevating energy expenditure.


Asunto(s)
Apetito , Leptina , Norepinefrina , Rayos Ultravioleta , Regulación hacia Arriba , Aumento de Peso , Animales , Ratones , Aumento de Peso/efectos de la radiación , Norepinefrina/metabolismo , Norepinefrina/sangre , Rayos Ultravioleta/efectos adversos , Leptina/sangre , Leptina/metabolismo , Regulación hacia Arriba/efectos de la radiación , Apetito/efectos de la radiación , Metabolismo Energético/efectos de la radiación , Masculino , Ratones Endogámicos C57BL , Obesidad/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/efectos de la radiación , Humanos , Modelos Animales de Enfermedad , Ingestión de Alimentos/efectos de la radiación , Ingestión de Alimentos/fisiología , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de la radiación
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