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1.
Medicina (Kaunas) ; 60(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38399541

RESUMO

We describe a rare and complex case of septic cavernous sinus thrombosis (SCST) in a 70-year-old patient who initially presented with ocular symptoms that rapidly progressed to severe intracranial vascular complications, including subarachnoid hemorrhage (SAH). Despite the use of broad-spectrum antibiotics and anticoagulants, the patient's condition deteriorated. SCST, often caused by sinus infections, presents a significant diagnostic and therapeutic dilemma, with mortality rates exceeding 20%. This report underscores the diversity of clinical presentations, ranging from mild headaches to severe cranial nerve deficits, that complicate diagnosis and treatment. The inability to detect any aneurysms in our patient using magnetic resonance imaging (MRI) and computed tomography angiography (CTA) may indicate an alternative pathogenesis. This could involve venous hypertension and endothelial hyperpermeability. This case illustrates the need for personalized treatment approaches, as recommended by the European Federation of Neurological Societies, and the importance of a multidisciplinary perspective when managing such intricate neurological conditions. Our findings contribute to the understanding of SCST coexisting with SAH.


Assuntos
Trombose do Corpo Cavernoso , Trombose dos Seios Intracranianos , Hemorragia Subaracnóidea , Humanos , Idoso , Trombose do Corpo Cavernoso/complicações , Trombose do Corpo Cavernoso/diagnóstico , Hemorragia Subaracnóidea/complicações , Trombose dos Seios Intracranianos/complicações , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/tratamento farmacológico , Anticoagulantes/uso terapêutico , Imageamento por Ressonância Magnética/efeitos adversos
2.
Oral Dis ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178608

RESUMO

OBJECTIVE: Immune checkpoint inhibitors (ICI) are recommended as the first-line therapy for platinum-refractory head and neck squamous cell carcinoma (HNSCC), a disease with a poor prognosis. However, biomarkers in this situation are rare. The objective was to identify radiomic features-associated biomarkers to guide the prognosis and treatment opinions in the era of ICI. METHODS: A total of 31 platinum-refractory HNSCC patients were retrospectively enrolled. Of these, 65.5% (20/31) received ICI-based therapy and 35.5% (11/31) did not. Radiomic features of the primary site at the onset of recurrent metastatic (R/M) status were extracted. Prognostic and predictive radiomic biomarkers were analysed. RESULTS: The median overall survival from R/M status (R/M OS) was 9.6 months. Grey-level co-occurrence matrix-associated texture features were the most important in identifying the patients with or without 9-month R/M death. A radiomic risk-stratification model was established and equally separated the patients into high-, intermittent- and lower-risk groups (1-year R/M death rate, 100.0% vs. 70.8% vs. 27.1%, p = 0.001). Short-run high grey-level emphasis (SRHGE) was more suitable than programmed death ligand 1 (PD-L1) expression in selecting whether patients received ICI-based therapy. CONCLUSIONS: Radiomic features were effective prognostic and predictive biomarkers. Future studies are warranted.

3.
Pharmaceuticals (Basel) ; 16(9)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37764996

RESUMO

BACKGROUND: The local tumor control rate of colon cancer by radiotherapy is unsatisfactory due to recurrence and radioresistance. Ginsenoside Rh2 (Rh2), a panoxadiol saponin, possesses various antitumor effects. METHODS: CT26/luc murine colon carcinoma cells and a CT26/luc tumor-bearing animal model were used to investigate the therapeutic efficacy of Rh2 combined with ionizing radiation and the underlying mechanisms. RESULTS: Rh2 caused cell cycle arrest at the G1 phase in CT26/luc cells; however, when combined with ionizing radiation, the cells were arrested at the G2/M phase. Rh2 was found to suppress the activity of NF-κB induced by radiation by inhibiting the MAPK pathway, consequently affecting the expression of effector proteins. In an in vivo study, the combination treatment significantly increased tumor growth delay time and overall survival. Furthermore, the combination treatment significantly reduced NF-κB and NF-κB-related effector proteins, along with PD-1 receptor expression. Additionally, Rh2 administration led to increased levels of interleukin-12, -18, and interferon-γ in the mice's sera. Importantly, biochemical analysis revealed no toxicities associated with Rh2 alone or combined with radiation. CONCLUSIONS: The combination of Rh2 with radiation may have potential as an alternative to improve the therapeutic efficacy of colorectal cancer.

4.
Quant Imaging Med Surg ; 13(8): 5355-5361, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37581037

RESUMO

This study investigated the efficacy and safety of transradial access (TRA) thyroid artery embolization (TAE) for patients with large solitary symptomatic benign thyroid nodules. Six patients with a total of six nodules (three men and three women; mean age, 36.3 years; age range, 23-45 years) underwent TRA TAE between October 2021 and June 2022 and were subsequently followed up three months later, and their cases were retrospectively reviewed. The associated complications were recorded during and after TRA TAE. The volume change and nodule-related symptom score on a 10-cm visual analogue scale (VAS) between baseline, 1- and 3-month follow-up was analyzed using Wilcoxon signed-rank test. The technical success rate of the TRA TAE was 100% without conversion to transfemoral access. The mean volume of the nodules decreased between baseline (84.1 mL; range, 46.1-170.5 mL), 1-month (38.8 mL; range, 17.6-91.5 mL; P=0.028) and 3-month (14.8 mL; range, 3.95-26.4 mL; P=0.068) at follow-up after TRA TAE. The mean volume reduction rate was 54.9% (range, 45.2-71.8%) at 1-month follow-up and 81.8% (range, 62.0-92.0%) at 3-month follow-up. The VAS score was reduced at 1-month (P=0.028) and at 3-month follow up (P=0.068). Radial artery spasm (n=1) was noted during TRA TAE, and neck pain (n=5) and voice change (n=1) occurred within 1 week after the procedure and resolved with conservative treatment. No major complications were reported. TRA TAE may be a promising alternative therapy for the management of large solitary thyroid nodules.

5.
J Health Popul Nutr ; 42(1): 16, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36890612

RESUMO

BACKGROUND: Uterine fibroids (UFs) are uterine smooth muscle neoplasms that affect women, especially during the reproductive stage. Both genetic and lifestyle factors affect the onset of the disease. We examined the association between the estrogen receptor 1 (ESR1) rs2234693 variant (whose genotypes are TT, TC, and CC) and UFs in Taiwanese premenopausal and postmenopausal women. METHODS: We linked individual-level data of 3588 participants from the Taiwan Biobank to the National Health Insurance Research Database at the Health and Welfare Data Science Center. The association of the ESR1 rs2234693 variant and other variables with UFs was determined by multiple logistic regression, and the results were presented as odds ratios and 95% confidence intervals (CIs). RESULTS: The 3588 participants comprised 622 cases and 2966 controls. In all the participants, the ESR1 rs2234693 TC and CC genotypes compared to the reference genotype (TT) were associated with a lower risk of UFs. However, the results were significant only for the CC genotype (OR; 95% CI = 0.70; 0.52-0.93). Noteworthy, the association of TC and CC with UFs was dose-dependent (p-trend = 0.012). Based on menopausal status, both TC and CC were significantly and dose-dependently associated with a lower risk of UFs in premenopausal women (OR; 95% CI = 0.76; 0.59-0.98 for TC and 0.64; 0.43-0.95 for CC: p-trend = 0.010). CONCLUSION: The TC and CC genotypes of the ESR1 rs2234693 variant may reduce susceptibility to UFs, especially in premenopausal women.


Assuntos
Receptor alfa de Estrogênio , Leiomioma , Polimorfismo de Nucleotídeo Único , Feminino , Humanos , Receptor alfa de Estrogênio/genética , Genótipo , Leiomioma/genética , Modelos Logísticos , Pós-Menopausa
6.
Pharmaceutics ; 14(6)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35745788

RESUMO

ß-sitosterol (SITO) has been reported with anticancer effects; however, with poor bioavailability. The current study aimed to investigate whether liposomal encapsulated ß-sitosterol (LS) has a better inhibition effect on tumor metastasis than ß-sitosterol in a CT26/luc lung metastasis mouse model and the possible underlying mechanism. LS was liposomal-encapsulated SITO and was delivered to mice by oral gavage. The cell viability was determined by the MTT assay, and invasiveness of the tumor cells and related protein expression were evaluated with the invasion assay and Western blotting. For therapeutic efficacy evaluation, male BALB/c mice were treated with PBS, SITO, and LS once a day for 7 days prior to intravenous injections of CT26/luc cells; treatments were continued twice a week post-cell inoculation throughout the entire experiment. Tumor growth inhibition was monitored by bioluminescent imaging (BLI). IL-12, IL-18, and IFN-γ in the intestinal epithelium were determined by ELISA. The results show that LS treatment had a better invasion inhibition with lower cytotoxicity than SITO when the same dose was utilized. Notably, mice treated with LS significantly exhibited fewer metastases to the lungs and other tissues/organs compared with the Control and SITO groups. Additionally, the IL-12, IL-18, and IFN-γ levels were significantly increased in the LS-treated mice compared with the Control and SITO groups. The underlying mechanism may be through the inhibition of MMP-9 and elicitation of the antitumoral Th1 immune response, such as increasing CD4+ and CD8+ T cells, IL-12, IL-18, and IFN-γ.

7.
Medicine (Baltimore) ; 101(11)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35356911

RESUMO

ABSTRACT: Tuberous sclerosis complex (TSC) is a rare genetic disorder with multisystem involvement. TSC is characterized by benign hamartomas in multiple organs, including the brain, and its clinical phenotypes may be associated with abnormal functional connections. We aimed to use resting-state functional connectivity to provide findings of disrupted functional brain networks in TSC patients using graph theoretical analysis (GTA) and network-based statistic (NBS) analysis.Forty TSC patients (age = 24.11+/-11.44 years old) and 18 age-matched (25.13+/- 10.01 years old) healthy controls were recruited; they underwent resting-state functional magnetic resonance imaging using a 3T magnetic resonance imaging scanner. After image preprocessing and removing physiological noises, GTA was used to calculate the topological parameters of the brain network. NBS analysis was then used to determine the differences in cerebrum functional connectivity between the 2 groups.In GTA, several topological parameters, including the clustering coefficient, local efficiency, transitivity, and modularity, were better in controls than in TSC patients (P < .05). In NBS analysis, the edges of the brain networks between the groups were compared. One subnetwork showed more edges in controls than in TSC patients (P < .05), including the connections from the frontal lobe to the temporal and parietal lobe.The study results provide the findings on disrupted functional connectivity and organization in TSC patients compared with controls. The findings may help better understand the underlying physiological mechanisms of brain connection in TSC.


Assuntos
Conectoma , Esclerose Tuberosa , Encéfalo/patologia , Conectoma/métodos , Interpretação Estatística de Dados , Humanos , Imageamento por Ressonância Magnética/métodos , Esclerose Tuberosa/diagnóstico por imagem , Esclerose Tuberosa/patologia
8.
J Transl Med ; 20(1): 87, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35164795

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is caused by a combination of environmental, genetic, and epigenetic factors including, fasting blood glucose (FBG), genetic variant rs841853, and cg19693031 methylation. We evaluated the interaction between rs841853 and cg19693031 on the FBG levels of non-diabetic Taiwanese adults. METHODS: We used Taiwan Biobank (TWB) data collected between 2008 and 2016. The TWB data source contains information on basic demographics, personal lifestyles, medical history, methylation, and genotype. The study participants included 1300 people with DNA methylation data. The association of cg19693031 methylation (stratified into quartiles) with rs841853 and FBG was determined using multiple linear regression analysis. The beta-coefficients (ß) and p-values were estimated. RESULTS: The mean ± standard deviation (SD) of FBG in rs841853-CC individuals (92.07 ± 7.78) did not differ significantly from that in the CA + AA individuals (91.62 ± 7.14). However, the cg19693031 methylation levels were significantly different in the two groups (0.7716 ± 0.05 in CC individuals and 0.7631 ± 0.05 in CA + AA individuals (p = 0.002). The cg19693031 methylation levels according to quartiles were ß < 0.738592 (< Q1), 0.738592 ≤ 0.769992 (Q1-Q2), 0.769992 ≤ 0.800918 (Q2-Q3), and ß ≥ 0.800918 (≥ Q3). FBG increased with decreasing cg19693031 methylation levels in a dose-response manner (ptrend = 0.005). The ß-coefficient was - 0.0236 (p = 0.965) for Q2-Q3, 1.0317 (p = 0.058) for Q1-Q2, and 1.3336 (p = 0.019 for < Q1 compared to the reference quartile (≥ Q3). The genetic variant rs841853 was not significantly associated with FBG. However, its interaction with cg19693031 methylation was significant (p-value = 0.036). Based on stratification by rs841853 genotypes, only the CC group retained the inverse and dose-response association between FBG and cg19693031 methylation. The ß (p-value) was 0.8082 (0.255) for Q2-Q3, 1.6930 (0.022) for Q1-Q2, and 2.2190 (0.004) for < Q1 compared to the reference quartile (≥ Q3). The ptrend was 0.002. CONCLUSION: Summarily, methylation at cg19693031 was inversely associated with fasting blood glucose in a dose-dependent manner. The inverse association was more prominent in rs841853-CC individuals, suggesting that rs841853 could modulate the association between cg19693031 methylation and FBG. Our results suggest that genetic variants may be involved in epigenetic mechanisms associated with FBG, a hallmark of diabetes. Therefore, integrating genetic and epigenetic data may provide more insight into the early-onset of diabetes.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Adulto , Proteínas de Transporte/genética , Metilação de DNA/genética , Diabetes Mellitus Tipo 2/genética , Jejum , Transportador de Glucose Tipo 1 , Humanos
9.
Medicine (Baltimore) ; 100(33): e27018, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414995

RESUMO

ABSTRACT: Breast cancer is the leading type of cancer among women worldwide, and a high number of breast cancer patients are suffering from psychological and cognitive disorders. This cross-sectional study used resting-state functional magnetic resonance imaging (rs-fMRI) and clinical neuropsychological tests to evaluate the possible underlying mechanisms.We enrolled 32 breast cancer patients without chemotherapy (BC), 32 breast cancer patients within 6 to 12 months after the completion of chemotherapy (BC_CTx) and 46 healthy controls. Participants underwent neuropsychological tests and rs-fMRI with mean fractional amplitude of low-frequency fluctuation and mean regional homogeneity analyses. Between groups whole-brain voxel-wise rs-fMRI comparisons were calculated using two-sample t test. rs-fMRI and neuropsychological tests correlation analyses were calculated using multiple regression. Age and years of education were used as covariates. A false discovery rate-corrected P-value of less than .05 was considered statistically significant.We found significantly alteration of mean fractional amplitude of low-frequency fluctuation and mean regional homogeneity in the frontoparietal lobe and occipital lobe in the BC group compared with the other 2 groups, indicating alteration of functional dorsal attention network (DAN). Furthermore, we found the DAN alteration was correlated with neuropsychological impairment.The majority of potential underlying mechanisms of DAN alteration in BC patients may due to insufficient frontoparietal lobe neural activity to drive DAN and may be related to the effects of neuropsychological distress. Further longitudinal studies with comprehensive images and neuropsychological tests correlations are recommended.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Neoplasias da Mama/tratamento farmacológico , Tratamento Farmacológico/estatística & dados numéricos , Sobreviventes/estatística & dados numéricos , Adulto , Ansiedade/etiologia , Ansiedade/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Neoplasias da Mama/complicações , Estudos Transversais , Depressão/etiologia , Depressão/psicologia , Tratamento Farmacológico/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Taiwan
10.
Artigo em Inglês | MEDLINE | ID: mdl-33946254

RESUMO

Previous studies have indicated that prenatal exposure to endocrine-disrupting chemicals (EDCs) can cause adverse neuropsychiatric disorders in children and adolescents. This study aimed to determine the association between the concentrations of prenatal EDCs and brain structure changes in teenagers by using MRI. We recruited 49 mother-child pairs during the third trimester of pregnancy, and collected and examined the concentration of EDCs-including phthalate esters, perfluorochemicals (PFCs), and heavy metals (lead, arsenic, cadmium, and mercury)-in maternal urine and/or serum. MRI voxel-based morphometry (VBM) and generalized q-sampling imaging (GQI) mapping-including generalized fractional anisotropy (GFA), normalized quantitative anisotropy (NQA), and the isotropic value of the orientation distribution function (ISO)-were obtained in teenagers 13-16 years of age in order to find the association between maternal EDC concentrations and possible brain structure alterations in the teenagers' brains. We found that there are several specific vulnerable brain areas/structures associated with prenatal exposure to EDCs, including decreased focal brain volume, primarily in the frontal lobe; high frontoparietal lobe, temporooccipital lobe and cerebellum; and white matter structural alterations, which showed a negative association with GFA/NQA and a positive association with ISO, primarily in the corpus callosum, external and internal capsules, corona radiata, superior fronto-occipital fasciculus, and superior longitudinal fasciculus. Prenatal exposure to EDCs may be associated with specific brain structure alterations in teenagers.


Assuntos
Disruptores Endócrinos , Efeitos Tardios da Exposição Pré-Natal , Substância Branca , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Disruptores Endócrinos/toxicidade , Feminino , Humanos , Imageamento por Ressonância Magnética , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Substância Branca/diagnóstico por imagem
11.
Front Neurol ; 12: 582149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897577

RESUMO

Aim: Unilateral vertebral artery hypoplasia is considered a risk factor for posterior circulation infarction. Despite the increasing attention on unilateral vertebral artery hypoplasia, few studies have discussed bilateral vertebral artery hypoplasia, its influence on stroke, or its collateral supply from the circle of Willis. We aimed to identify its characteristics, stroke pattern, and unique ultrasonographic and brain imaging findings. Materials and Methods: Of the 1,301 consecutive in-patients diagnosed with acute ischemic stroke from January 2013 to December 2015, medical and laboratory data and stroke or transient ischemic attack history were recorded. We enrolled patients who underwent both brain magnetic resonance imaging and sonography examinations. Vertebral artery and posterior cerebral artery analyses were conducted in accordance with clinical criteria. Results: Adequate imaging data were available for 467 patients. Of these, eight patients met the criteria for bilateral vertebral artery hypoplasia. The mean age was 62.9 ± 12.1 years. There were six male (75.0%) and two female patients (25.0%). A high prevalence of hypertension (7/8, 87.5%) was noted. Sonograms displayed a very low net flow volume in the vertebral arteries, with the average net flow volume being 28.9 ± 9.7 mL/min. A high frequency (6/8; 75.0%) of the fetal variant posterior cerebral artery from the carotids was found. The infarction patterns in these patients were all bilateral, scattered, and in multiple vascular territories. Conclusion: Patients with bilateral vertebral hypoplasia displayed a unique collateral supply, special stroke pattern, and younger stroke onset. Early recognition and stroke prevention should be considered critical in clinical practice.

12.
MAGMA ; 34(2): 189-200, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32715372

RESUMO

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome with variable and unpredictable neurological comorbidity that includes epilepsy, intellectual disability (ID), autism spectrum disorder, and neurobehavioral abnormalities. The degree of white matter involvement is believed to be associated with the severity of neurological impairment. The goal of the present study was to evaluate diffusion characteristics of tubers, white matter lesions, and brain structural network alterations in TSC patients using diffusion tensor imaging (DTI), graph theoretical analysis (GTA), and network-based statistical (NBS) analysis. MATERIALS AND METHODS: Forty-two patients with a definitive diagnosis of TSC were recruited for this study. All patients underwent brain DTI examination using a 3 T magnetic resonance imaging system. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) values, and fractional anisotropy (FA) mapping in 52 tubers and white matter lesions were measured and compared with those of contralateral normal regions. GTA was performed on the inter-regional connectivity matrix, and NBS analysis was used to identify the significance of any connected subnetworks evident in the set of altered connections. For neurological severity subgrouping, a neurological severity score was assigned to TSC patients including those with ID, seizure, autism, and other neuropsychiatric disorders (NPDs). RESULTS: Significantly higher MD, AD, and RD, and lower FA values, were found in TSC lesions compared with those measured in contralateral normal regions for tubers (P < 0.05). GTA and NBS analysis provided better local segregation but worse global integration of the structural network (regular-like network) in TSC patients with ID, seizure, and higher Neurological Severity Score. Disrupted subnetworks in TSC patients with severe status included connections from the frontal lobe to the parietal lobe, temporal lobe to the caudate, and temporal lobe to the insula. DISCUSSION: DTI has the potential to provide valuable information about cytoarchitectural changes in TSC lesions beyond morphological MRI findings alone. Using GTA and NBS, current results provide the information of disrupted white matter connectivity and organization in TSC patients with different neuropsychological impairments.


Assuntos
Transtorno do Espectro Autista , Conectoma , Esclerose Tuberosa , Substância Branca , Encéfalo , Imagem de Tensor de Difusão , Humanos
13.
Environ Health Prev Med ; 25(1): 68, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153431

RESUMO

BACKGROUND: Particulate matter (PM) < 2.5 µm (PM2.5) or fine PM is a serious public health concern. It affects DNA methylation and heightens carcinogenesis. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene. However, aberrant methylation of the gene is associated with several cancers. We evaluated the association between PM2.5 and DLEC1 promoter methylation in Taiwanese adults based on regular outdoor exercise. METHODS: We obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM2.5 data from the Air Quality Monitoring Database (AQMD) and estimated participants' exposure using residential addresses. RESULTS: DLEC1 methylation and PM2.5 were positively associated: beta coefficient (ß) = 0.114 × 10-3; p value = 0.046. The test for interaction between exercise and PM2.5 on DLEC1 methylation was significant (p value = 0.036). After stratification by exercise habits, PM2.5 and DLEC1 methylation remained significantly associated only among those who exercised regularly (ß = 0.237 × 10-3; p value = 0.007). PM2.5 quartile-stratified analyses revealed an inverse association between regular exercise and DLEC1 methylation at PM2.5 < 27.37 µg/m3 (ß = - 5.280 × 10-3; p value = 0.009). After combining exercise habits and PM2.5 quartiles, one stratum (i.e., regular exercise and PM2.5 < 27.37 µg/m3) was inversely associated with DLEC1 methylation (ß = -5.160 × 10-3, p value = 0.007). CONCLUSIONS: We found significant positive associations between PM2.5 and DLEC1 promoter methylation. Regular exercise at PM2.5 < 27.37 µg/m3 seemingly regulated DLEC1 promoter methylation.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Metilação de DNA/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Exercício Físico , Material Particulado/efeitos adversos , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan
14.
Int J Mol Sci ; 21(12)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575632

RESUMO

Glioblastoma, the most common and aggressive brain tumor with low survival rate, is difficult to be cured by neurosurgery or radiotherapy. Mounting evidence has reported the anti-inflammatory and anticancer effects of curcumin on several types of cancer in preclinical studies and clinical trials. To our knowledge, there is no platform or system that could be used to effectively and real-timely evaluate the therapeutic efficacy of curcumin for glioblastoma multiforme (GBM). In this study, we constructed a lentivirus vector with triple-reporter genes (Fluc/GFP/tk) and transduced into rat F98 glioblastoma cells to establish an orthotopic F98/FGT glioma-bearing rat model. In the model, the therapeutic efficacies for curcumin alone, radiation alone, and their combination were evaluated via noninvasive bioluminescent imaging and overall survival measurements. At the cell level, curcumin is capable of causing a G2/M cell cycle arrest and sensitizing the F98 cells to radiation. In animal model, curcumin synergistically enhances the effects of radiotherapy on suppressing the growth of both transplanted glioma cells and in situ brain tumors, and extending the overall survival periods longer than those of curcumin alone and radiation alone treatments. In conclusion, we have demonstrated that curcumin may serve as a novel radiosensitizer to combine with radiotherapy using the triple-reporter F98/FGT animal model for effective and simultaneous evaluation of therapeutic efficacy.


Assuntos
Neoplasias Encefálicas/terapia , Curcumina/administração & dosagem , Glioblastoma/terapia , Lentivirus/genética , Radiossensibilizantes/administração & dosagem , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimiorradioterapia , Curcumina/farmacologia , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Luciferases/genética , Luciferases/metabolismo , Imageamento por Ressonância Magnética , Radiossensibilizantes/farmacologia , Ratos , Ratos Transgênicos , Timidina Quinase/genética , Timidina Quinase/metabolismo , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Brain Struct Funct ; 225(5): 1669-1684, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32448957

RESUMO

Many studies have reported that prenatal exposure to endocrine-disrupting chemicals (EDCs) can cause adverse behavioral effects or cognitive dysfunction in children. This study aimed to investigate a relationship of the concentration of prenatal EDCs and brain function in teenagers. We recruited 59 mother-child pairs during the third trimester of pregnancy, and collected and examined the concentration of EDCs, such as heavy metals, phthalates and perfluoroalkyl substances (PFASs), in maternal urine and serum. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected in teenagers 13-16 years of age, and fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) were performed to find the association between maternal EDC concentrations and the functional development of the teenage brain. We found a correlation between MBP concentration and activity in the superior frontal gyrus, middle frontal gyrus, middle temporal gyrus and inferior temporal gyrus in the combined group of boys and girls. We also observed a correlation between MBzP concentration and activity in the anterior cingulum gyrus and insula in girls. We found a correlation between lead concentration and activity in the cuneus in the combined group. We also observed a correlation between MeHg concentration and activity in the superior temporal gyrus, caudate nucleus and putamen in the combined group. The PFOS results revealed a negative relationship between activity in the right putamen in boys, girls and the combined group after phthalate or heavy metals were applied as covariates. The PFNA results showed a negative correlation between activity in the left/right putamen and left caudate nucleus in boys, girls and the combined group after phthalate, heavy metals or PFOS were applied as covariates. We examined the correlations between maternal EDC concentrations and brain development and found that the associations with resting-state teenage brains in some circumstances are sex-related.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Disruptores Endócrinos/toxicidade , Exposição Ambiental/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adolescente , Mapeamento Encefálico , Disruptores Endócrinos/sangue , Disruptores Endócrinos/urina , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Gravidez
16.
J Ultrasound Med ; 38(11): 3037-3042, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31020689

RESUMO

OBJECTIVES: Vertebrobasilar dolichoectasia (VBD) and vertebral artery hypoplasia (VAH) are known predisposing factors of posterior circulation stokes. These vascular conditions have unique hemodynamic patterns in neuroimaging studies; however, they have been presented as a single entity in some reports. The aim of this retrospective study was to clarify the relationship between these conditions with regard to ultrasound (US) findings. METHODS: A total of 465 patients with strokes were recruited. Brain magnetic resonance imaging of vertebrobasilar arteries and differences in extracranial side-to-side vertebral artery (VA) flow were recorded by US and compared in groups. RESULTS: The mean age of the 465 patients ± SD was 67.23 ± 12.13 years; 296 were men. The prevalence of VBD was 13.5% (n = 63), and 10.8% (n = 50) of the patients had coexisting VAH and VBD. These patients also had the highest prevalence of posterior circulation strokes (58% [n = 29]). A cutoff value of 55.65 mL/min and a ratio discrepancy of 5.28 (group median) for the side-to-side extracranial VA flow volume as detected by conventional US were also observed in the patients with both VAH and VBD. CONCLUSIONS: Our study revealed a higher prevalence of posterior circulation strokes in the patients with both VBD and VAH. Chronic asymmetric hemodynamic shear force in extracranial VAs leading to deformity of the vertebrobasilar system may explain our observations. Accordingly, the blood flow volume and the ratio difference could potentially be used to detect patients at risk of VBD and reduce stroke risk factors.


Assuntos
Ultrassonografia/métodos , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/fisiopatologia , Insuficiência Vertebrobasilar/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Doenças Vasculares/diagnóstico por imagem , Insuficiência Vertebrobasilar/fisiopatologia
17.
Sci Rep ; 9(1): 104, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30643203

RESUMO

Breast cancer is the most common cancer among women worldwide. Adjuvant chemotherapy has significantly reduced mortality but increased cognitive impairments, including attention function, making quality of life issues a crucial concern. This study enrolled nineteen breast cancer patients who were treated with standard chemotherapy within 6 months and 20 sex-matched healthy controls to investigate the brain effects of chemotherapy. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) with mean fractional amplitude of low-frequency fluctuation (mfALFF) analysis and were correlated with neuropsychological tests, including the Mini-Mental State Examination (MMSE), the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R), and the Impact of Event Scale-Revised (IES-R), to explore the possible underlying mechanism of cognitive alternations. We found increased mfALFF over the frontoparietal lobe and decreased mfALFF over the occipital lobe in the cancer patients compared with the healthy controls; the altered brain regions may be associated with the dorsal attention network (DAN) and may be explained by a compensatory mechanism. Both MMSE and CAMS-R scores showed a positive correlation with mfALFF in the occipital lobe but a negative correlation in the frontoparietal lobe. By contrast, IES-R scores showed a positive correlation with mfALFF in the frontoparietal lobe but a negative correlation in the occipital lobe. These alterations are potentially related to the effects of both chemotherapy and psychological distress. Future research involving a larger sample size of patients with breast cancer is recommended.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Transtornos Cognitivos/induzido quimicamente , Tratamento Farmacológico/métodos , Adulto , Antineoplásicos/administração & dosagem , Encéfalo/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Testes Neuropsicológicos
18.
PeerJ ; 5: e3147, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29181274

RESUMO

Major depressive disorder (MDD) is highly prevalent, recurrent, and associated with functional impairment, morbidity, and mortality. Herein, we aimed to identify disruptions in functional connectomics among subjects with MDD by using resting-state functional magnetic resonance imaging (rs-fMRI). Sixteen subjects with MDD and thirty health controls completed resting-state fMRI scans and clinical assessments (e.g., Hamilton Depression Rating Scale (HAMD) and Hospital Anxiety and Depression Scale (HADS)). We found higher amplitude of low frequency fluctuations (ALFF) bilaterally in the hippocampus and amygdala among MDD subjects when compared to healthy controls. Using graph theoretical analysis, we found decreased clustering coefficient, local efficiency, and transitivity in the MDD patients. Our findings suggest a potential biomarker for differentiating individuals with MDD from individuals without MDD.

19.
Neuroimage Clin ; 15: 376-382, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28580294

RESUMO

The question of whether there are biological differences between male and female brains is a fraught one, and political positions and prior expectations seem to have a strong influence on the interpretation of scientific data in this field. This question is relevant to issues of gender differences in the prevalence of psychiatric conditions, including autism, attention deficit hyperactivity disorder (ADHD), Tourette's syndrome, schizophrenia, dyslexia, depression, and eating disorders. Understanding how gender influences vulnerability to these conditions is significant. Diffusion magnetic resonance imaging (dMRI) provides a non-invasive method to investigate brain microstructure and the integrity of anatomical connectivity. Generalized q-sampling imaging (GQI) has been proposed to characterize complicated fiber patterns and distinguish fiber orientations, providing an opportunity for more accurate, higher-order descriptions through the water diffusion process. Therefore, we aimed to investigate differences in the brain's structural network between teenage males and females using GQI. This study included 59 (i.e., 33 males and 26 females) age- and education-matched subjects (age range: 13 to 14 years). The structural connectome was obtained by graph theoretical and network-based statistical (NBS) analyses. Our findings show that teenage male brains exhibit better intrahemispheric communication, and teenage female brains exhibit better interhemispheric communication. Our results also suggest that the network organization of teenage male brains is more local, more segregated, and more similar to small-world networks than teenage female brains. We conclude that the use of an MRI study with a GQI-based structural connectomic approach like ours presents novel insights into network-based systems of the brain and provides a new piece of the puzzle regarding gender differences.


Assuntos
Encéfalo/diagnóstico por imagem , Conectoma , Imagem de Difusão por Ressonância Magnética/métodos , Caracteres Sexuais , Adolescente , Feminino , Humanos , Masculino
20.
J Affect Disord ; 205: 103-111, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27423425

RESUMO

BACKGROUND: It is hypothesized that the phenomenology of major depressive disorder (MDD) is subserved by disturbances in the structure and function of brain circuits; however, findings of structural abnormalities using MRI have been inconsistent. Generalized q-sampling imaging (GQI) methodology provides an opportunity to assess the functional integrity of white matter tracts in implicated circuits. METHODS: The study population was comprised of 16 outpatients with MDD (mean age 44.81±2.2 years) and 30 age- and gender-matched healthy controls (mean age 45.03±1.88 years). We excluded participants with any other primary mental disorder, substance use disorder, or any neurological illnesses. We used T1-weighted 3D MRI with voxel-based morphometry (VBM) and vertex-wise shape analysis, and GQI with voxel-based statistical analysis (VBA), graph theoretical analysis (GTA) and network-based statistical (NBS) analysis to evaluate brain structure and connectivity abnormalities in MDD compared to healthy controls correlates with clinical measures of depressive symptom severity, Hamilton Depression Rating Scale 17-item (HAMD) and Hospital Anxiety and Depression Scale (HADS). RESULTS: Using VBM and vertex-wise shape analyses, we found significant volumetric decreases in the hippocampus and amygdala among subjects with MDD (p<0.001). Using GQI, we found decreases in diffusion anisotropy in the superior longitudinal fasciculus and increases in diffusion probability distribution in the frontal lobe among subjects with MDD (p<0.01). In GTA and NBS analyses, we found several disruptions in connectivity among subjects with MDD, particularly in the frontal lobes (p<0.05). In addition, structural alterations were correlated with depressive symptom severity (p<0.01). LIMITATIONS: Small sample size; the cross-sectional design did not allow us to observe treatment effects in the MDD participants. CONCLUSIONS: Our results provide further evidence indicating that MDD may be conceptualized as a brain disorder with abnormal circuit structure and connectivity.


Assuntos
Encéfalo/patologia , Conectoma , Transtorno Depressivo Maior/patologia , Rede Nervosa/patologia , Adulto , Tonsila do Cerebelo/patologia , Anisotropia , Estudos Transversais , Transtorno Depressivo Maior/diagnóstico , Feminino , Lobo Frontal/fisiopatologia , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Substância Branca/fisiopatologia
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