RESUMO
Hyperalgesia occurs in the orofacial region of rats when estrogen levels are low, although the specific mechanism needs to be investigated further. Furthermore, oxidative stress plays an important role in the transmission of pain signals. This study aimed to explore the role of oxidative stress in orofacial hyperalgesia under low estrogen conditions. We firstly found an imbalance between oxidative and antioxidant capacity within the spinal trigeminal subnucleus caudalis (SP5C) of rats after ovariectomy (OVX), resulting in oxidative stress and then a decrease in the orofacial pain threshold. To investigate the mechanism by which oxidative stress occurs, we used virus as a tool to silence or overexpress the excitatory amino acid transporter 3 (EAAT3) gene. Further investigation revealed that the regulation of glutathione (GSH) and reactive oxygen species (ROS) can be achieved by regulating EAAT3, which in turn impacts the occurrence of oxidative stress. In summary, our findings suggest that reduced expression of EAAT3 within the SP5C of rats in the low estrogen state may decrease GSH content and increase ROS levels, resulting in oxidative stress and ultimately lead to orofacial hyperalgesia. This suggests that antioxidants could be a potential therapeutic direction for orofacial hyperalgesia under low estrogen conditions, though more research is needed to understand its mechanism.
Assuntos
Estrogênios , Transportador 3 de Aminoácido Excitatório , Dor Facial , Glutationa , Hiperalgesia , Ovariectomia , Estresse Oxidativo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Animais , Hiperalgesia/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Feminino , Estrogênios/metabolismo , Estrogênios/farmacologia , Dor Facial/metabolismo , Glutationa/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transportador 3 de Aminoácido Excitatório/metabolismo , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Núcleo Inferior Caudal do Nervo Trigêmeo/metabolismo , Núcleo Inferior Caudal do Nervo Trigêmeo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismoRESUMO
OBJECTIVES: There is a strong association among risk factors for oral cancer (ORCA), such as smoking, alcohol consumption, fiber intake, and red meat intake. The apparent synergistic effects reported in previous observational studies may also underestimate the independent effects. Our study aims to further explore the potential etiology and causality of oral cancer. MATERIALS AND METHODS: This study used the genome-wide associations study database (GWAS) in European populations for Mendelian randomization (MR) analysis to explore exposure factors associated with ORCA and detect the genetic causality between these exposures and ORCA risk. RESULTS: Our results demonstrated that in univariate MR analysis, the five exposure factors (celery intake, average weekly beer and cider intake, spirits intake, and pork intake) were risk factors, and oily fish intake was a safety factor, but in multivariate MR analysis, pork intake had the greatest impact on oral cancer when the five food/drink intakes were simultaneously consumed. CONCLUSIONS: The causal relationship between the five exposure factors (oily fish intake, celery intake, pork intake, average weekly beer and cider intake, and spirits intake) and oral cancer was analyzed. The causal effects of pork on oral cancer may be underestimated. CLINICAL RELEVANCE: Prevention of oral cancer requires better education about lifestyle-related risk factors, and improved awareness and tools for early diagnosis. Our study provides some risk factors that cannot be ignored for the cause prevention of oral cancer, such as pork intake, and its role in oral cancer prevention and control.
Assuntos
Neoplasias Bucais , Animais , Consumo de Bebidas Alcoólicas , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias Bucais/etiologia , Neoplasias Bucais/genética , Fatores de Risco , Humanos , Carne , SuínosRESUMO
Abstract Objective The aim of this study was to evaluate the serum Syndecan-1 (SDC-1) levels in patients with immunoglobulin-A vasculitis (IgAV) in children and its relation with gastrointestinal involvements. Methods Sixty-eight children with IgAV and 48 healthy children were enrolled in this cross-sectional study. Clinical and related laboratory data were collected from a computerized hospital database. Serum SDC-1 was collected on admission prior to treatment. Results Forty-eight patients fully met the IgAV diagnostic criteria at admission (IgAV group), 20 patients with rash only and diagnosed IgAV during hospitalization (Purpura group). In IgAV group, 30 patients with gastrointestinal involvements (IgAV-GI group) and 18 patients without gastrointestinal involvements (IgAV-NGI group). SDC-1 serum levels were significantly higher in the IgAV group (86.37 ng/mL (IQR 59.16-117.14 ng/mL)) than in the controls (20.37 ng/mL (IQR 15.52-26.45 ng/mL)) and the Purpura group (32.66 ng/mL (IQR 14.87-49.89 ng/mL)). Additionally, SDC-1 (OR = 1.08) was independently associated with IgAV with a cut-off value (sensitivity and specificity) of 66.55 ng/mL (68.8%, 95.0%), and the area under the curve was 0.908. The serum SDC-1 levels of the IgAV-GI group (106.92 ± 50.12 ng/mL) were significantly higher than those in the IgAV-NGI group (67.52 ± 17.59 ng/mL). Logistic regression analysis showed that SDC-1 (OR = 1.03) was independently associated with IgAV-GI with a cut-off value of 89.39 ng/mL. Conclusions SDC-1 serum levels may mirror vascular endothelium injury and mucosal damage in IgAV. Its applicability as a surrogate biomarker in IgAV remains to be determined.
RESUMO
To explore the value of blood routine examination indexes in the differential diagnosis of immunoglobulin A vasculitis (IgAV) with abdominal involvement and appendicitis in children. Forty-seven patients with IgAV and abdominal involvement, 95 cases with appendicitis, and 48 healthy children were enrolled in this study. Demographic and laboratory data were retrospectively recorded from medical files. The levels of serum percentage of lymphocytes (LYM%), percentage of eosinophils (E%), red cell volume distribution width (RDW) and platelet (PLT) count were higher, while blood cells (WBC) count, percentage of neutrophils (N%), percentage of monocytes (M%), mean platelet volume (MPV), platelet distribution width and C-reactive protein were lower in the group of IgAV with abdominal involvement compared to appendicitis group (P < 0.05). Multivariate logistic regression analysis showed LYM% (odds ratio (OR) = 1.34, P = 0.001) and RDW (OR = 2.96, P = 0.045) were independent risk factors for IgAV with abdominal involvement. N% (OR = 1.270, P = 0.006) and MPV (OR = 51.15, P = 0.042) were independently associated with appendicitis. Using receiver operating characteristic analysis, the optimal cut-off values (sensitivity and specificity) respectively were 42.17% (95.7%, 100.0%) for LYM%, 12.65% (83.0%, 83.2%) for RDW, 61.5% (91.6%, 97.9%) for NE% and 10.1fL (78.9%, 75.4%) for MPV, with the AUC values of 0.989, 0.881, 0.985, 0.810, respectively. Blood routine examination indices, especially the N%, LYM%, RDW, and MPV, can be used for simple differential diagnosis of IgAV with abdominal involvement and appendicitis.
Assuntos
Apendicite , Vasculite , Apendicite/diagnóstico , Proteína C-Reativa , Criança , Diagnóstico Diferencial , Humanos , Imunoglobulina A , Estudos Retrospectivos , Vasculite/diagnósticoAssuntos
Biópsia Guiada por Imagem/métodos , Sarcoma de Células de Langerhans/patologia , Linfonodos/patologia , Tomografia Computadorizada por Raios X/métodos , Diarreia/diagnóstico , Diarreia/etiologia , Progressão da Doença , Febre/diagnóstico , Febre/etiologia , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Lactente , Sarcoma de Células de Langerhans/diagnóstico , Sarcoma de Células de Langerhans/terapia , Masculino , Prognóstico , Doenças RarasRESUMO
OBJECTIVE: To construct angiogenesis-specific RGD10-NGR9 dual-targeting superparamagnetic iron oxide nanoparticles, and to evaluate its magnetic resonamce imaging (MRI) features in nude mice and potential diagnostic value in tumor MRI. METHODS: Dual-targeting peptides RGD10-NGR9 were designed and synthesized. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were synthesized by chemical co-precipitation method and the surface was modified to be hydrophilic by coating with dextran. The dual-targeting peptides RGD10-NGR9 were conjugated to USPIO. Cell binding affinity and up-taking ability of the dual-targeting USPIO nanoparticles to integrin ανß3-APN positive cells were subsequently tested by Prussian blue staining and phenanthroline colorimetry in vitro. The RGD10-NGR9 conjugated with USPIO was injected intravenously into xenograft mice, which were scanned by MRI at predetermined time points. The MRI and contrast-to-noise ratio (CNR) values were calculated to evaluate the ability of dual-targeting USPIO as a potential contrast agent in nude mice. RESULTS: P-CLN-Dextran-USPIO nanoparticles with stable physical properties were successfully constructed. The average diameter of Fe3O4 nanoparticles was 8-10 nm, that of Dextran-USPIO was about 20 nm and P-CLN-Dextran-USPIO had an average diameter about 30 nm. The in vitro studies showed a better specificity of dual-targeting USPIO nanoparticles on proliferating human umbilical vein endothelia cells (HUVEC). In vivo, RGD10-NGR9-USPIO showed a significantly reduced contrast in signal intensity and 2.83-times increased the CNR in the tumor MRI in xenograft mice. CONCLUSION: This novel synthesized RGD10-NGR9 dual-targeting USPIO is with better specific affinity in vitro and in vivo, and might be used as a molecular contrast agent for tumor angiogenesis MRI.