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Background The diagnostic abilities of multimodal large language models (LLMs) using direct image inputs and the impact of the temperature parameter of LLMs remain unexplored. Purpose To investigate the ability of GPT-4V and Gemini Pro Vision in generating differential diagnoses at different temperatures compared with radiologists using Radiology Diagnosis Please cases. Materials and Methods This retrospective study included Diagnosis Please cases published from January 2008 to October 2023. Input images included original images and captures of the textual patient history and figure legends (without imaging findings) from PDF files of each case. The LLMs were tasked with providing three differential diagnoses, repeated five times at temperatures 0, 0.5, and 1. Eight subspecialty-trained radiologists solved cases. An experienced radiologist compared generated and final diagnoses, considering the result correct if the generated diagnoses included the final diagnosis after five repetitions. Accuracy was assessed across models, temperatures, and radiology subspecialties, with statistical significance set at P < .007 after Bonferroni correction for multiple comparisons across the LLMs at the three temperatures and with radiologists. Results A total of 190 cases were included in neuroradiology (n = 53), multisystem (n = 27), gastrointestinal (n = 25), genitourinary (n = 23), musculoskeletal (n = 17), chest (n = 16), cardiovascular (n = 12), pediatric (n = 12), and breast (n = 5) subspecialties. Overall accuracy improved with increasing temperature settings (0, 0.5, 1) for both GPT-4V (41% [78 of 190 cases], 45% [86 of 190 cases], 49% [93 of 190 cases], respectively) and Gemini Pro Vision (29% [55 of 190 cases], 36% [69 of 190 cases], 39% [74 of 190 cases], respectively), although there was no evidence of a statistically significant difference after Bonferroni adjustment (GPT-4V, P = .12; Gemini Pro Vision, P = .04). The overall accuracy of radiologists (61% [115 of 190 cases]) was higher than that of Gemini Pro Vision at temperature 1 (T1) (P < .001), while no statistically significant difference was observed between radiologists and GPT-4V at T1 after Bonferroni adjustment (P = .02). Radiologists (range, 45%-88%) outperformed the LLMs at T1 (range, 24%-75%) in most subspecialties. Conclusion Using direct radiologic image inputs, GPT-4V and Gemini Pro Vision showed improved diagnostic accuracy with increasing temperature settings. Although GPT-4V slightly underperformed compared with radiologists, it nonetheless demonstrated promising potential as a supportive tool in diagnostic decision-making. © RSNA, 2024 See also the editorial by Nishino and Ballard in this issue.
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Radiologistas , Humanos , Estudos Retrospectivos , Diagnóstico Diferencial , Interpretação de Imagem Assistida por Computador/métodos , FemininoRESUMO
OBJECTIVES: To develop and validate an automatic classification algorithm for diagnosing Alzheimer's disease (AD) or mild cognitive impairment (MCI). METHODS AND MATERIALS: This study evaluated a high-performance interpretable network algorithm (TabNet) and compared its performance with that of XGBoost, a widely used classifier. Brain segmentation was performed using a commercially approved software. TabNet and XGBoost were trained on the volumes or radiomics features of 102 segmented regions for classifying subjects into AD, MCI, or cognitively normal (CN) groups. The diagnostic performances of the two algorithms were compared using areas under the curves (AUCs). Additionally, 20 deep learning-based AD signature areas were investigated. RESULTS: Between December 2014 and March 2017, 161 AD, 153 MCI, and 306 CN cases were enrolled. Another 120 AD, 90 MCI, and 141 CN cases were included for the internal validation. Public datasets were used for external validation. TabNet with volume features had an AUC of 0.951 (95% confidence interval [CI], 0.947-0.955) for AD vs CN, which was similar to that of XGBoost (0.953 [95% CI, 0.951-0.955], p = 0.41). External validation revealed the similar performances of two classifiers using volume features (0.871 vs. 0.871, p = 0.86). Likewise, two algorithms showed similar performances with one another in classifying MCI. The addition of radiomics data did not improve the performance of TabNet. TabNet and XGBoost focused on the same 13/20 regions of interest, including the hippocampus, inferior lateral ventricle, and entorhinal cortex. CONCLUSIONS: TabNet shows high performance in AD classification and detailed interpretation of the selected regions. CLINICAL RELEVANCE STATEMENT: Using a high-performance interpretable deep learning network, the automatic classification algorithm assisted in accurate Alzheimer's disease detection using 3D T1-weighted brain MRI and detailed interpretation of the selected regions. KEY POINTS: ⢠MR volumetry data revealed that TabNet had a high diagnostic performance in differentiating Alzheimer's disease (AD) from cognitive normal cases, which was comparable with that of XGBoost. ⢠The addition of radiomics data to the volume data did not improve the diagnostic performance of TabNet. ⢠Both TabNet and XGBoost selected the clinically meaningful regions of interest in AD, including the hippocampus, inferior lateral ventricle, and entorhinal cortex.
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Doença de Alzheimer , Aprendizado Profundo , Humanos , Doença de Alzheimer/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Algoritmos , Hipocampo/diagnóstico por imagemRESUMO
This study developed a method for quantifying eight short-chain fatty acids (SCFAs) in mouse fecal samples using solid-phase microextraction (SPME) coupled with triple quadrupole gas chromatography tandem mass spectrometry. Furthermore, significant factors affecting SCFA analysis, including SPME fiber selection, pH, salting-out agent, and sample collection time, were investigated. Contrary to previous studies, we found that the CAR/PDMS fiber had the highest extraction efficiency for all SCFAs. The optimal extraction efficiency was observed at pH 2.0, particularly for low-molecular-weight SCFAs. NaH2PO4 showed a more effective extraction efficiency than NaCl, owing to its pH stability and less interference with the solvent matrix. Additionally, our results showed that the SCFA concentration increased over collection time. The composition ratio of the eight SCFAs was maintained for up to 24 h; thus, we concluded that samples should be collected within four hours to obtain reliable results. Our findings may improve laboratory methods for SCFA extraction and mouse fecal sample analysis.
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Osteoarthritis is one of the leading conditions that promote the consumption of these dietary supplements. Chondroitin sulfate, glucosamine, and methylsulfonylmethane are among the prominent alternative treatments for osteoarthritis. In this study, these dietary supplements were incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes, and the formation of marker metabolites was measured to investigate their inhibitory potential on cytochrome P450 enzyme activities. The results revealed no significant inhibitory effects on seven CYPs, consistent with established related research data. Therefore, these substances are anticipated to have a low potential for cytochrome P450-mediated drug interactions with osteoarthritis medications that are likely to be co-administered. However, given the previous reports of interaction cases involving glucosamine, caution is advised regarding dietary supplement-drug interactions.
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Glucosamina , Osteoartrite , Humanos , Glucosamina/farmacologia , Sulfatos de Condroitina/uso terapêutico , Suplementos Nutricionais , Osteoartrite/tratamento farmacológico , Interações Medicamentosas , Sistema Enzimático do Citocromo P-450RESUMO
OBJECTIVE: To evaluate the diagnostic performance of hippocampal volumetry for Alzheimer's disease (AD) or mild cognitive impairment (MCI). METHODS: The MEDLINE and Embase databases were searched for articles that evaluated the diagnostic performance of hippocampal volumetry in differentiating AD or MCI from normal controls, published up to March 6, 2022. The quality of the articles was evaluated by the QUADAS-2 tool. A bivariate random-effects model was used to pool sensitivity, specificity, and area under the curve. Sensitivity analysis and meta-regression were conducted to explain study heterogeneity. The diagnostic performance of entorhinal cortex volumetry was also pooled. RESULTS: Thirty-three articles (5157 patients) were included. The pooled sensitivity and specificity for AD were 82% (95% confidence interval [CI], 77-86%) and 87% (95% CI, 82-91%), whereas those for MCI were 60% (95% CI, 51-69%) and 75% (95% CI, 67-81%), respectively. No difference in the diagnostic performance was observed between automatic and manual segmentation (p = 0.11). MMSE scores, study design, and the reference standard being used were associated with study heterogeneity (p < 0.01). Subgroup analysis demonstrated a higher diagnostic performance of entorhinal cortex volumetry for both AD (pooled sensitivity: 88% vs. 79%, specificity: 92% vs. 89%, p = 0.07) and MCI (pooled sensitivity: 71% vs. 55%, specificity: 83% vs. 68%, p = 0.06). CONCLUSIONS: Our meta-analysis demonstrated good diagnostic performance of hippocampal volumetry for AD or MCI. Entorhinal cortex volumetry might have superior diagnostic performance to hippocampal volumetry. However, due to a small number of studies, the diagnostic performance of entorhinal cortex volumetry is yet to be determined. KEY POINTS: ⢠The pooled sensitivity and specificity of hippocampal volumetry for Alzheimer's disease were 82% and 87%, whereas those for mild cognitive impairment were 60% and 75%, respectively. ⢠No significant difference in the diagnostic performance was observed between automatic and manual segmentation. ⢠Subgroup analysis demonstrated superior diagnostic performance of entorhinal cortex volumetry for AD (pooled sensitivity: 88%, specificity: 92%) and MCI (pooled sensitivity: 71%, specificity: 83%).
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To evaluate clinico-radiologic markers that predict poor overall survival (OS) in sporadic Creutzfeldt-Jakob disease (sCJD) and to develop a prognostic model. MATERIALS AND METHODS: Patients with newly diagnosed sCJD were included who underwent diffusion-weighted imaging (DWI) from February 2000 to July 2020. The impact of 9 clinico-radiologic features on OS was analyzed using univariable and multivariable Cox proportional hazards regression model. The DWI prognostic score model was generated. The weighted kappa was calculated for interobserver agreement. RESULTS: Sixty patients (mean age ± SD, 61.0 ± 9.7 years, 32 women) were included. Univariable analysis showed positive associations between poor OS and patient age (p = 0.003), extent of involved cortical lobes (p = 0.11), involvement of caudate nucleus (p = 0.07), and putamen (p = 0.04). Multivariable analysis demonstrated two independent prognostic factors: age ≥ 60 (HR 2.65, 95% CI, 1.41-4.98), and diffusion restriction in caudate nucleus and putamen (HR 2.24, 95% CI, 1.15-4.37). Based on these features, the DWI prognostic score model was generated: low-risk (0-1 point), intermediate-risk (2-3 points), and high-risk (4-5 points) groups. Median OS in high-risk group was 1.7 months, which was significantly shorter than those in the intermediate-risk (14.2 months) and low-risk (26.5 months) groups (p < 0.001). Interobserver agreements were excellent (κ = 0.91-0.92). CONCLUSIONS: Our study demonstrated that age and diffusion restriction in caudate nucleus and putamen were the independent prognostic factors of poor overall survival in sporadic Creutzfeldt-Jakob disease. Our DWI prognostic score model may be useful in clinical settings for disease stratification. KEY POINTS: ⢠Age ≥ 60, and diffusion restriction in caudate nucleus and putamen were the independent prognostic factors of poor overall survival in sCJD. ⢠Based on our DWI prognostic score model, median overall survival in high-risk group was 1.7 months, which was significantly shorter than those in the intermediate-risk group (14.2 months) and low-risk group (26.5 months) (p < 0.001). ⢠The proposed DWI prognostic score model may be useful in clinical settings for disease stratification.
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Síndrome de Creutzfeldt-Jakob , Núcleo Caudado , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Prognóstico , PutamenRESUMO
BACKGROUND: Chronic fatigue syndrome (CFS) is a long-term disabling illness accompanied by medically unexplained fatigue. This study aimed to explore the epidemiological characteristics of CFS in South Korea. METHODS: Using the nationwide medical records provided by the Korean Health Insurance Review & Assessment Service (HIRA), we analyzed the entire dataset for CFS patients diagnosed by physicians in South Korea from January 2010 to December 2020. RESULTS: The annual mean incidence of CFS was estimated to be 44.71 ± 6.10 cases per 100,000 individuals [95% CI: 40.57, 48.76], and the prevalence rate was 57.70 ± 12.20 cases per 100,000 individuals [95% CI: 49.40, 65.79]. These two rates increased by 1.53- and 1.94-fold from 2010 to 2020, respectively, and showed an increasing trend with aging and an approximately 1.5-fold female predominance. CONCLUSIONS: This study is the first to report the nationwide epidemiological features of CFS, which reflects the clinical reality of CFS diagnosis and care in South Korea. This study will be a valuable reference for studies of CFS in the future.
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Síndrome de Fadiga Crônica , Síndrome de Fadiga Crônica/complicações , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/epidemiologia , Feminino , Humanos , Incidência , Prevalência , República da Coreia/epidemiologiaRESUMO
Polysaccharides that contain many sugar monomers include starch and non-starch polysaccharides (NSPs) together with resistant starch (RS). Dietary polysaccharides are well known to have a wide range of biological benefits for bowel health. Gut microbiota and their fermentative products, short chain fatty acids (SCFA), which have recently been highlighted as metabolic regulators, are thought to mediate the function of dietary complex carbohydrates and bowel health. We discuss the influence of various polysaccharides on human bowel health and the mechanisms underlying these effects. We also describe their biological effects on intestinal health and the mechanisms underlying their activity; the polysaccharides were divided into three categories: dietary, microbial, and host-derived polysaccharides. Physiological impacts of non-starch polysaccharides (NSPs) and resistant starch (RS), both of which pass through the small intestine nearly intact and can be fermented by gut microbiota in the large intestine, are similar to each other. They exert a wide range of beneficial effects including anti-inflammation, gut epithelial barrier protection, and immune modulation through both microbiota-dependent and -independent mechanisms. Bacterial polysaccharides usually found in the cell wall generally act as immune modulators, and host-derived polysaccharides not only protect host cells from pathogenic microbial neighbors but also affect overall intestinal health via interactions with gut microbes. Considering these observations, further studies on polysaccharides will be important for bowel health.
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Microbioma Gastrointestinal , Carboidratos da Dieta , Ácidos Graxos Voláteis , Humanos , Polissacarídeos , AmidoRESUMO
OBJECTIVE: To evaluate the diagnostic performance and reliability of the medial temporal lobe atrophy (MTA) scale in patients with Alzheimer's disease. METHODS: A systematic literature search of MEDLINE and EMBASE databases was performed to select studies that evaluated the diagnostic performance or reliability of MTA scale, published up to January 21, 2021. Pooled estimates of sensitivity and specificity were calculated using a bivariate random-effects model. Pooled correlation coefficients for intra- and interobserver agreements were calculated using the random-effects model based on Fisher's Z transformation of correlations. Meta-regression was performed to explain the study heterogeneity. Subgroup analysis was performed to compare the diagnostic performance of the MTA scale and hippocampal volumetry. RESULTS: Twenty-one original articles were included. The pooled sensitivity and specificity of the MTA scale in differentiating Alzheimer's disease from healthy control were 74% (95% CI, 68-79%) and 88% (95% CI, 83-91%), respectively. The area under the curve of the MTA scale was 0.88 (95% CI, 0.84-0.90). Meta-regression demonstrated that the difference in the method of rating the MTA scale was significantly associated with study heterogeneity (p = 0.04). No significant difference was observed in five studies regarding the diagnostic performance between MTA scale and hippocampal volumetry (p = 0.40). The pooled correlation coefficients for intra- and interobserver agreements were 0.85 (95% CI, 0.69-0.93) and 0.83 (95% CI, 0.66-0.92), respectively. CONCLUSIONS: Our meta-analysis demonstrated a good diagnostic performance and reliability of the MTA scale in Alzheimer's disease. KEY POINTS: ⢠The pooled sensitivity and specificity of the MTA scale in differentiating Alzheimer's disease from healthy control were 74% and 88%, respectively. ⢠There was no significant difference in the diagnostic performance between MTA scale and hippocampal volumetry. ⢠The reliability of MTA scale was excellent based on the pooled correlation coefficient for intra- and interobserver agreements.
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Doença de Alzheimer , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Atrofia/patologia , Humanos , Imageamento por Ressonância Magnética , Reprodutibilidade dos Testes , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologiaRESUMO
OBJECTIVE: To evaluate the diagnostic yield and performance of DWI in patients with sporadic CJD (sCJD). METHODS: A systematic literature search of the MEDLINE and EMBASE databases was performed, since their inception up to July 28, 2020. Pooled diagnostic yield of diffusion-weighted imaging was calculated using DerSimonian-Laird random-effects model. Pooled diagnostic performance of DWI (sensitivity, specificity, and area under the curve) in diagnosing sCJD among patients with rapidly progressive dementia was calculated using a bivariate random-effects model. Subgroup analysis and meta-regression were performed. RESULTS: Fifteen original articles with a total of 1144 patients with sCJD were included. The pooled diagnostic yield was 91% (95% confidence interval [CI], 86 to 94%); summary sensitivity, 91% (95% CI, 84 to 95%); and specificity, 97% (95% CI, 94 to 99%). The area under the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI, 0.97-0.99). Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on DWI followed by striatum, thalamus, and cerebellum. Subgroup analysis and meta-regression demonstrated significant heterogeneity among the studies associated with the reference standards used for diagnosis of sCJD. CONCLUSIONS: DWI showed excellent diagnostic value in diagnosis of sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia. Simultaneous involvement of the neocortex and striatum was the most common finding, and the neocortex was the most common site to be involved on diffusion-weighted imaging followed by striatum, thalamus, and cerebellum. KEY POINTS: ⢠The pooled diagnostic yield of diffusion-weighted imaging in sporadic Creutzfeldt-Jakob disease was 91%. ⢠The diagnostic performance of diffusion-weighted imaging for predicting sporadic Creutzfeldt-Jakob disease among patients with rapidly progressive dementia was excellent, with pooled sensitivity, 91%, and specificity, 97%. ⢠Simultaneous involvement in the neocortex and striatum was most commonly seen on diffusion-weighted imaging (60%), followed by the neocortex without striatum (30%), thalamus (21%), cerebellum (8%), and striatum without neocortex (7%).
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Síndrome de Creutzfeldt-Jakob , Encefalopatia Espongiforme Bovina , Animais , Encéfalo/diagnóstico por imagem , Bovinos , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética , TálamoRESUMO
OBJECTIVE: To evaluate the diagnostic performance and interobserver agreement of the callosal angle and Evans' index in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A systematic search of MEDLINE and EMBASE was performed to find studies assessing the diagnostic performance or interobserver agreement of the callosal angle and Evans' index in iNPH. Pooled sensitivity and specificity of the two radiologic indices were calculated. The area under the curve (AUC) was obtained based on a hierarchical summary receiver operating characteristic curve. The diagnostic performances of both radiologic indices were compared in subgroup analysis. To evaluate interobserver agreement, the pooled correlation coefficient was calculated. RESULTS: Ten original articles (874 patients) were included. The pooled sensitivity and specificity of the callosal angle in the diagnosis of iNPH were 91% (95% CI, 86-94%) and 93% (95% CI, 89-96%), respectively. The pooled sensitivity and specificity of Evans' index were 96% (95% CI, 47-100%) and 83% (95% CI, 77-88%), respectively. Subgroup analysis demonstrated a significant higher specificity of the callosal angle than that of Evans' index (p < 0.01). The AUC of the callosal angle and Evans' index were 0.97 (95% CI, 0.95-0.98) and 0.87 (95% CI, 0.84-0.90), respectively. The pooled correlation coefficients for the callosal angle and Evans' index were 0.92 (95% CI, 0.82-0.96) and 0.92 (95% CI, 0.83-0.97), respectively. CONCLUSIONS: Our meta-analysis demonstrated a high performance of the callosal angle in the diagnosis of iNPH. Evans' index showed reasonable diagnostic performance with high sensitivity but low specificity. Interobserver agreements were excellent in both radiologic indices. KEY POINTS: ⢠Callosal angle showed high diagnostic performance in idiopathic normal pressure hydrocephalus. ⢠Evans' index showed reasonable diagnostic performance with high sensitivity but low specificity. ⢠Interobserver agreements were excellent in both callosal angle and Evans' index.
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Hidrocefalia de Pressão Normal , Corpo Caloso/diagnóstico por imagem , Humanos , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Variações Dependentes do Observador , Curva ROC , Sensibilidade e EspecificidadeRESUMO
BACKGROUND. Several guidelines recommend body imaging for the initial work-up of patients with suspected primary CNS lymphoma, to exclude subclinical systemic involvement. However, to our knowledge, the diagnostic yield of body CT (contrast-enhanced CT of the chest, abdomen, and pelvis) and whole-body FDG PET/CT for the evaluation of subclinical systemic lymphoma has not yet been systematically evaluated. OBJECTIVE. The purpose of this study was to investigate and compare the diagnostic yield of body CT and whole-body FDG PET/CT in detecting subclinical systemic lymphoma in patients with suspected primary CNS lymphoma. EVIDENCE ACQUISITION. A systematic search of the MEDLINE and EMBASE databases through July 5, 2020, was conducted to identify studies evaluating the diagnostic yield of body CT or whole-body FDG PET/CT in detecting subclinical systemic lymphoma in patients with suspected primary CNS lymphoma. Pooled estimates of the diagnostic yield of both imaging modalities were calculated using the DerSimonian and Laird random-effects model. The false referral rate and the rate of incidental secondary malignancy were also pooled. EVIDENCE SYNTHESIS. Nine original articles on studies evaluating a total of 1040 patients were included. In detecting subclinical systemic lymphoma, the pooled diagnostic yields of body CT and whole-body FDG PET/CT were 2.5% (95% CI, 1.5-3.9%) and 4.9% (95% CI, 2.8-8.5%), respectively. In the subgroup analysis, the diagnostic yield of whole-body FDG PET/CT was significantly higher than that of body CT (p = .03). Four studies reported changes in the management plan: the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) regimen with or without radiation therapy was added if extracranial lymphoma involvement was detected by body CT or whole-body FDG PET/CT. The pooled false referral rate of whole-body FDG PET/CT was 5.3% (95% CI, 2.2-12.0%). The pooled rate of incidental secondary malignancy detected on whole-body FDG PET/CT was 3.1% (95% CI, 1.7-5.6%). CONCLUSION. Body imaging should be used in the initial workup of patients with suspected primary CNS lymphoma, to exclude systemic involvement. Whole-body FDG PET/CT may be a better alternative to body CT. CLINICAL IMPACT. Our results support current National Comprehensive Cancer Network guidelines for the use of body imaging to exclude subclinical systemic involvement in patients with suspected primary CNS lymphoma.
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Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Fluordesoxiglucose F18 , Linfoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total/métodos , Neoplasias do Sistema Nervoso Central/patologia , Humanos , Linfoma/patologia , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Diabetic nephropathy (DN) is one of the most significant microvascular complications in diabetic patients. DN is the leading cause of end-stage renal disease, accounting for approximately 50% of incident cases. The current treatment options, such as optimal control of hyperglycemia and elevated blood pressure, are insufficient to prevent its progression. DN has been considered as a nonimmune, metabolic, or hemodynamic glomerular disease initiated by hyperglycemia. However, recent studies suggest that DN is an inflammatory disease, and immune cells related with innate and adaptive immunity, such as macrophage and T cells, might be involved in its development and progression. Although it has been revealed that kidney dendritic cells (DCs) accumulation in the renal tissue of human and animal models of DN require activated T cells in the kidney disease, little is known about the function of DCs in DN. In this review, we describe kidney DCs and their subsets, and the role in the pathogenesis of DN. We also suggest how to improve the kidney outcomes by modulating kidney DCs optimally in the patients with DN.
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Células Dendríticas/imunologia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/patologia , Ativação Linfocitária/imunologia , Animais , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/etiologia , HumanosRESUMO
PURPOSE: Metabolic diseases caused by high-carbohydrate and/or high-salt diets are becoming major public health concerns. However, the effects of salt on high-carbohydrate diet-induced obesity are unclear. Accordingly, in this study, we investigated the effects of high-salt intake on high-carbohydrate diet-induced obesity. METHODS: We performed a 12-week study on gut microbiota and metabolic changes in high-rice diet (HRD) or HRD supplemented with high-salt (HRS)-fed C57BL/6 J mice by 16S rRNA analysis, glucose and insulin tolerance testing, gut barrier function, western blot and histological analysis. Moreover, the effects of salt on lipid metabolism were confirmed in vitro using 3T3-L1 cells. RESULTS: High salt intake decreased HRD-induced increases in body and white adipose tissue (WAT) weight. Alternatively, HRS did not reverse the observed increases in glucose intolerance and insulin resistance. Moreover, HRD caused changes in the gut microbiota, thereby impairing gut barrier function and increasing inflammation in the liver. HRS altered HRD-induced microbial composition, however, did not ameliorate gut barrier dysfunction or hepatic inflammation. HRS diets regulated the HRD-induced increase in peroxisome proliferator-activated receptor-γ (PPAR-γ) and lipid metabolism-related protein expression. Moreover, within WAT, HRS was found to reverse the observed decrease in adiponectin and increase in PPAR-γ expression induced by HRD. In vitro, high NaCl concentration also significantly reduced 3T3-L1 cell differentiation and modulated lipid metabolism without causing cytotoxicity. CONCLUSION: These results indicate that high salt intake ameliorates metabolic changes associated with a high-rice diet, including changes in fecal microbiota composition.
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Microbioma Gastrointestinal , Doenças Metabólicas , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S , Cloreto de Sódio , Cloreto de Sódio na Dieta/efeitos adversosRESUMO
The present study investigates the immunomodulatory activities of buckwheat polysaccharide fraction (BPF) from the seed of Fagopyrum esculentum on RAW 264.7 macrophage cell line and Cyclophosphamide-induced immunosuppressed conditions in mice models. The results of in vitro showed that treatment with 0.5-10⯵g/mL of BPF can modulate immune responses. MTT assay and nitric oxide production and immune-related cytokine levels were conducted. Treatment with BPF at a dose of 10⯵g/mL of BPF increased immune responses on macrophages. Moreover, natural killer (NK) cell cytotoxicity was conducted. The apoptosis of YAC-1â¯cells increased as the co-culture ratio between spleen cells and YAC-1â¯cells increased approximately 4- fold compared to the control group from 12.5:1 to 50.0:1. The in-vivo immunomodulatory effects of BPF were evaluated by cyclophosphamide-induced mice model. The immune response of BPF was determined against cyclophosphamide (100â¯mg/kg) immunosuppressed mice at doses of 50â¯mg/kg and 100â¯mg/kg of BPF as compared to control. The results of this study showed that BPF administration increased spleen and thymus indices as well as the leukocytes count in the blood of immunosuppressed mice. All of results suggested that BPF are potentially acts as immunomodulator for activation of immune responses.
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Fagopyrum/química , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Fatores Imunológicos/administração & dosagem , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Fracionamento Químico/métodos , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Células RAW 264.7 , Sementes/químicaRESUMO
PURPOSE: We analyzed the clinicopathologic characteristics and prognosis of pregnancy-associated breast cancer (PABC) according to clinical subtypes to better understand the characteristics of PABC. METHODS: A total of 83,792 female patients between the ages of 20 and 49 were enrolled in the Korean Breast Cancer Society Registry database from January 1, 1996 to December 31, 2015. 'PABC' is defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. Other patients were defined as 'non-PABC' patients. RESULTS: In non-PABC patients, luminal A subtype was the most common (50.2%). In PABC patients, TNBC was the most common (40.4%) subtype, while luminal A comprised 21.2% and HER2 subtype comprised 17.3%. There was a significant difference in overall survival (OS). In non-PABC patients, TNBC had the highest HR (HR 2.3, 95% CI 2.1-2.6). In PABC patients, the luminal B subtype (HR+ HER2-high Ki67) had the highest HR at 7.0 (95% CI 1.7-29.1). In multivariate analysis of OS by subtypes, PABC patients had significantly higher HR than non-PABC patients in the HER2 subtype (HR 2.0, 95% CI 1.1-3.7) and luminal B subtype (HR+ HER2-high Ki67) (HR 4.4, 95% CI 1.6-12.3). CONCLUSION: PABC showed different biologic features than non-PABC. PABC had a particularly poor prognosis in the luminal B (HR+ HER2-highKi67) and HER2 subtypes. To improve the prognosis of PABC, treatment should be considered according to subtype. Development of drugs that can be used during pregnancy is needed.
Assuntos
Biomarcadores Tumorais/genética , Complicações Neoplásicas na Gravidez/patologia , Prognóstico , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Gravidez , Complicações Neoplásicas na Gravidez/classificação , Complicações Neoplásicas na Gravidez/epidemiologia , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
Spatholobus suberectus (SS) is a medicinal herb commonly used in Asia to treat anemia, menoxenia and rheumatism. However, its effect of diabetes-induced renal damage and mechanisms of action against advanced glycation end-products (AGEs) are unclear. In this study, we evaluated the effects of SS on diabetes-induced renal damage and explored the possible underlying mechanisms using db/db type 2 diabetes mice. db/db mice were administered SS extract (50 mg/kg) orally for 6 weeks. SS-treated group did not change body weight, blood glucose and glycated hemoglobin (HbA1c) levels. However, SS treatment reversed diabetes-induced dyslipidemia and urinary albumin/creatinine ratio in db/db mice. Moreover, SS administration showed significantly increased protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a transcription factor for antioxidant enzyme. SS significantly upregulated glyoxalase 1 (Glo1) and NADPH quinine oxidoreductase 1 (NQO1) expression but reduced CML accumulation and downregulated receptor for AGEs (RAGE). Furthermore, SS showed significant decrease of periodic acidâ»Schiff (PAS)-positive staining and AGEs accumulation in histological and immunohistochemical analyses of kidney tissues. Taken together, we concluded that SS ameliorated the renal damage by inhibiting diabetes-induced glucotoxicity, dyslipidemia and oxidative stress, through the Nrf2/antioxidant responsive element (ARE) stress-response system.
Assuntos
Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Fabaceae/química , Produtos Finais de Glicação Avançada/metabolismo , Extratos Vegetais/farmacologia , Animais , Nefropatias Diabéticas/tratamento farmacológico , Modelos Animais de Doenças , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Imuno-Histoquímica , Isoflavonas/química , Isoflavonas/farmacologia , Lactoilglutationa Liase/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacosRESUMO
The medical records of 7 patients who underwent percutaneous transparaumbilical embolization of spontaneous portosystemic shunts for treatment of hepatic encephalopathy (HE) were retrospectively reviewed. Technical success was achieved in 100% (7/7) of patients. Four patients had complete resolution and 3 had improvement of signs and symptoms of HE within 3 days after the procedure for a clinical success rate of 100% (7/7). New-onset esophageal varices, a major complication, occurred in 1 patient. No other major complications were encountered. HE recurred in 71.4% (5/7) of patients during a median follow-up period of 43 months (range, 4-111 months).
Assuntos
Embolização Terapêutica/métodos , Encefalopatia Hepática/diagnóstico por imagem , Encefalopatia Hepática/terapia , Umbigo , Idoso , Angiografia Digital , Feminino , Humanos , Circulação Hepática , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Ovalbumin (OA) is the most abundant ingredient of chicken egg-white allergenic proteins. In the present study we investigated the possibility of reducing OA allergenicity by treatment with a natural protein exhibiting N-acetylglucosaminidase (NA) activity. Ascidian is cultivated as a food resource in northeast Asia. The ascidian viscera NA (AVNA) with almost no other exoglycosidases or proteolytic enzymes was isolated by applying size-exclusion chromatography to a protein precipitate of ascidian viscera. Intact OA was mixed with AVNA containing 0.2, 1.0, and 5.0 Units of NA. Anion-exchange chromatography was then used to isolate OA from AVNA-treated OA. The electrophoretic patterns and N-glycans of each isolated OA from AVNA-treated OA (iOA) were analyzed, and the terminal N-acetylglucosamines of iOA were selectively cleaved with no other degradation occurring. A competitive indirect enzyme-linked immunosorbent assay using rabbit anti-OA sera was performed to investigate the allergenicity of iOA, which was found to be significantly reduced depending on the increased NA activity compared to that of intact OA. These results indicate that OA allergenicity was reduced using a simple and mild treatment process with AVNA, and suggest that ascidian NA is an efficient natural protein for reducing the allergenicity of OA without requiring the use of harsh physical treatments or chemical conjugation.
Assuntos
Acetilglucosaminidase/metabolismo , Alérgenos/metabolismo , Ovalbumina/metabolismo , Urocordados/enzimologia , Acetilglucosaminidase/isolamento & purificação , Alérgenos/imunologia , Animais , Galinhas , Clara de Ovo/análise , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/prevenção & controle , Ovalbumina/imunologia , Coelhos , Vísceras/enzimologiaRESUMO
Rice bran, a by-product of brown rice milling, is a rich source of dietary fiber and protein, and its usage as a functional food is expected to increase. In this study, immunomodulatory effects of glycoprotein obtained from rice bran were studied in normal mice and mouse models of cyclophosphamide-induced immunosuppression. We prepared glycoprotein from rice bran by using ammonium precipitation and anion chromatography techniques. Different doses of glycoprotein from rice bran (10, 25, and 50 mg/kg) were administered orally for 28 days. On day 21, cyclophosphamide at a dose of 100 mg/kg was administered intraperitoneally. Glycoprotein from rice bran showed a significant dose-dependent restoration of the spleen index and white blood cell count in the immunocompromised mice. Glycoprotein from rice bran affected the immunomodulatory function by inducing the proliferation of splenic lymphocytes, which produce potential T and B cells. Moreover, it prevented cyclophosphamide-induced damage of Th1-type immunomodulatory function through enhanced secretion of Th1-type cytokines (interferon-γ and interleukin-12). These results indicate that glycoprotein from rice bran significantly recovered cyclophosphamide-induced immunosuppression. Based on these data, it was concluded that glycoprotein from rice bran is a potent immunomodulator and can be developed to recover the immunity of immunocompromised individuals.