RESUMO
Lipophilic shellfish toxins (LSTs) can cause human illness and therefore represent a serious threat to public health. Shellfish are the main dietary source of LSTs, but very few studies have appraised dietary exposure to LSTs through shellfish consumption in China. We measured levels of multiple LSTs in shellfish samples sold in the principal wholesale seafood market in the southern coastal city of Shenzhen, and we estimated the potential for acute and chronic LST exposure of the Shenzhen population via ingestion of shellfish. LST contamination data were obtained from a total of 14 species of 188 commercial samples. Eleven individual LSTs, namely okadaic acid (OA), dinophysis toxin-1 and -2 (DTX1 and DTX2), pectenotoxin-2 (PTX2), yessotoxin and homo yessotoxin (YTX and hYTX), azaspiracid-1, -2 and -3 (AZA1, AZA2, AZA3), spirolides (SPXs), and gymnodimine (GYM), were determined using liquid chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-MS/MS). More than two thirds of samples showed undetectable LSTs, while the detection rates (the proportion of samples with detectable LSTs) of individual LSTs ranged from 0% to 45.7%. Most shellfish samples had lower levels of LST contamination than the corresponding limits of detection (LODs), while some samples had levels of hYTX and GYM that exceeded the limits of quantification (LOQs). Overall, levels of LSTs in the 188 samples were below the regulatory limits set by most countries. Acute and chronic exposures of LST were estimated by a point-estimate modeling method that combined sample contamination data with consumption data from dietary survey of Shenzhen residents and consumption figures proposed by EFSA, the European Food Safety Authority. Seasonal variations in LST concentrations were noted in some instances. Overall, the estimated acute exposure to LSTs based on consumption of large-size shellfish portions and the maximum LSTs contamination level were below the provisional acute reference doses (ARfDs) proposed by the EFSA. Chronic exposure estimates based on mean and 99th percentile consumption of shellfish by Shenzhen residents and mean LSTs contamination levels in the collected samples were from 2452 to 74 times lower than those associated with estimated acute exposure levels.
Assuntos
Exposição Dietética/análise , Exposição Dietética/estatística & dados numéricos , Contaminação de Alimentos/análise , Contaminação de Alimentos/estatística & dados numéricos , Frutos do Mar/análise , Animais , Cromatografia Líquida , Dinoflagellida/química , Humanos , Toxinas Marinhas/análise , Alimentos Marinhos/análise , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: To compare the DNA methylation-related alteration induced by trichloroethylene (TCE) in human hepatic L-02 cells (L-02 cells) and SET deficient cells, and reveal the role of SET on the mechanisms in TCE-induced epigenetic pathway. METHODS: The L-02 cells and pre-established SET deficient cells were treated with different TCE concentrations, and the changes of total cell viability, DNA methylation level and DNA methyltransferases (DNMTs) activity were measured, respectively. In addition, the TCE-induced alteration in the protein expression of DNMT1, DNMT3a and DNMT3b were analyzed by Western blotting. RESULTS: After treatment with TCE for 24 h, the cell proliferation level was significantly decreased in both cell lines. When concentrations of TCE were 0, 1.0, 2.0, 4.0 and 8.0 mmol/L, the proliferation levels of L-02 cells were 100.00±2.70, 83.34±2.38, 75.56±4.51, 71.67±2.77 and 66.67±1.63, respectively (F = 58.29, P < 0.001); the cell proliferation levels of SET deficient cells were 101.12±1.67, 85.01±2.33, 79.44±1.67, 78.337±3.89 and 76.11±3.33, respectively (F = 42.41, P < 0.001). When concentration of TCE reached 4.0 mmol/L, the difference of cell proliferation level between two groups was statistically significant (t = -3.51; P = 0.013). After treated by TCE for 24 h, the global DNA methylation significantly decreased in both cell lines (F value was 212.87 and 79.32, respectively, P < 0.001). The difference between two groups was not statistically significant. After treated by TCE for 24 h, the methyltransferases activities were significantly decreased in both cell cells (F values were 77.92 and 113.80, respectively, P-0.001). The SET deficiency could inhibit the decrease of methyltransferases activity under TCE treatment. When the concentration of TCE reached 8.0 mmol/L, the enzymatic activity of L-02 cells and SET deficient cells decreased to 67.61%±2.85% and 72.97%± 1.94%, respectively. The difference between two groups was statistically significant (t = -3.94, P = 0.008). After treated with TCE for 24 h, concentrations of TCE were 0, 1.0, 2.0, 4.0 and 8.0 mmol/L, and the relative protein levels of DNMT1 in normal L-02 cells increased significantly to 1.00±0.03, 1.28±0.04, 1.20±0.04, 1.62±0.05, 1.43±0.04 (F = 103.00, P < 0.001); In SET deficient cells, the expressions of DNMT1 were 1.00±0.04, 0.96±0.02, 1.19±0.05, 0.85±0.03, 0.83±0.03, which was significantly down-regulated under TCE treatment (F = 44.18, P < 0.001). CONCLUSION: SET deficiency can significantly attenuate the TCE-induced decreases of cell viability and DNMTs activity, as well as alteration of protein expression of DNMT1 in L-02 cells, which indicated that SET was involved in the mechanism of TCE-induced cytotoxicity and epigenetic pathway in L-02 cells.
Assuntos
DNA (Citosina-5-)-Metiltransferases , Metilação de DNA , Tricloroetileno , Linhagem Celular , Sobrevivência Celular , DNA (Citosina-5-)-Metiltransferase 1 , DNA Metiltransferase 3A , Humanos , Fígado , DNA Metiltransferase 3BRESUMO
Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Chaperonas de Histonas/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Proteínas de Ligação a DNA , Feminino , Técnicas de Silenciamento de Genes , Chaperonas de Histonas/genética , Chaperonas de Histonas/fisiologia , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/fisiopatologia , Invasividade Neoplásica/prevenção & controle , Proteína Fosfatase 2/antagonistas & inibidores , Proteína Fosfatase 2/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologiaRESUMO
In order to explore the diagnostic value of magnetic resonance imaging (MRI) for neural activity among abnormal brain regions in patients with major depressive disorder (MDD), thirty patients with MDD (observation group) were selected for comparison with 30 healthy people without MDD (control group). The included subjects were examined by MRI to compare the MRI features and were analyzed for regional homogeneity (ReHo) and amplitude low-frequency fluctuations (ALFF). The results showed that compared with the control group, the brain regions with increased ReHo and ALFF in the observation group were medial frontal gyrus (right), middle temporal lobe (left), inferior parietal lobe (left), and posterior cerebellar lobe (right); the brain region with increased ReHo and ALFF in the observation group was the middle temporal gyrus (right). Compared with the control group, there were significant differences in ReHo and ALFF in the observation group. It was found that the brain function of patients with MDD was abnormal compared with that of the normal subjects, and the brain network activity was also abnormal. MRI features can be used to explore abnormal brain regions in patients with MDD and have positive guiding value.
Assuntos
Transtorno Depressivo Maior , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
Alzheimer's disease (AD) is a complex and progressive neurodegenerative disease with impaired synapse, imbalanced mineral metabolism, protein mis-folding and aggregation. Bis(ethylmaltolato)oxidovanadium(IV) (BEOV), an organic bioactive vanadium compound with low toxicity and high bioavailability, has been studied as therapeutic agent against tuberculosis and diabetes. However, its neuroprotective effects have rarely been reported. Therefore, in this study, the potential application of BEOV in intervening AD cognitive dysfunction and neuropathology was evaluated. Both low- and high-dose of BEOV (0.2 mmol/L and 1.0 mmol/L) supplementation for 2 months improved the spatial learning and memory deficits of the triple-transgenic AD (3 × Tg AD) mice and mitigated the loss of synaptic proteins and synaptic dysfunction. By inhibiting the expression of amyloid-ß precursor protein and ß-secretase, and the phosphorylation of tau protein at Ser262, Ser396, Ser404, and Ser202/Thr205 residues, BEOV reduced the amyloid-ß deposition and neurofibrillary tangle formation in AD mouse brains and primarily cultured neurons. Further analysis of the brain ionome revealed that BEOV supplementation could significantly affect the concentrations of a variety of metals, most of which, including several AD risk metals, showed reduced levels, particularly with a high-dose intake. Additionally, the elemental correlation network identified both conserved and specific elemental correlations, implying a highly complex and dynamic crosstalk between vanadium and other elements during long-term BEOV supplementation. Overall, our results suggest that BEOV is effective in AD intervention via both ameliorating the disease related pathology and regulating metal homeostasis.
Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Doenças Neurodegenerativas/metabolismo , Vanádio/metabolismo , Vanádio/farmacologia , Proteínas tau/genética , Proteínas tau/metabolismoRESUMO
Paralytic shellfish toxins (PSTs) produced by certain marine dinoflagellates accumulate in filter-feeding marine bivalves. We used LC-MS/MS to detect and quantify 13 PSTs in 188 shellfish samples of 14 species collected from Shenzhen city's Buji seafood wholesale market from March 2019 to February 2020. Twenty-six of 188 shellfish samples (13.8%) were PSTs detectable. Within 14 species, 10 out of 34 noble clam Chlamys nobilis samples contain detectable PSTs with the highest detection rate 29.4%. Seven out of 17 samples from Nan'ao island contained detectable PSTs with the highest detection rate 41.2% among 11 origins. Samples containing PSTs were concentrated in spring and winter, with the highest levels in March>December>January. Among PSTs detected, C1 was dominant. Acute dietary exposure assessment for Shenzhen residents were based on mean adult body weight, 99th percentile daily shellfish consumption of Shenzhen food consumption survey 2008 and maximum PSTs concentration for each shellfish species. The outcome for Chlamys nobilis was 2.4~3.7-fold higher than recommended ARfDs. Mean PSTs concentration, P99, and mean shellfish consumption were used to assess chronic dietary exposure. The results were lower than recommended ARfDs. In conclusion, residents in Shenzhen are at risk for acute PSTs poisoning, while relatively safe from chronic PSTs exposure.
Assuntos
Intoxicação por Frutos do Mar , Animais , Cromatografia Líquida , Exposição Dietética , Toxinas Marinhas , Saxitoxina/análise , Alimentos Marinhos/análise , Frutos do Mar/análise , Espectrometria de Massas em TandemRESUMO
An 81-year-old male patient presented to the department of gastroenterology with increasing lower abdominal pain for 2 years, aggravated with bloody stool for 1 month. Computed tomographic examination revealed a huge cyst (207 × 93 × 208 mm3) in the abdominal cavity, absence of bladder, thickening and strengthening of the rectal wall, and benign prostatic hyperplasia. Colonoscopy showed colon cancer and surgery was planned. Interestingly, after magnetic resonance imaging and cystography, we found colon cancer and a large bladder diverticulum rather than tumor metastasis or others. Severe bacteremia occurred in the elderly chronic obstructive pulmonary disease patient before operation. After careful consideration, we decided to take a large risk and combined urology and gastrointestinal surgery professionals to carry out bladder diverticulectomy, cystostomy, radical resection of rectal carcinoma, and so on. Fortunately, the patient recovered well after the operation. In addition to the common tumor metastasis and cystadenoma, the abdominal mass should also be alert to the rare bladder diverticulum, which eventually leads to diagnostic confusion. Multidisciplinary diagnosis and treatment has become an important treatment for complex diseases.
RESUMO
Neuronal apoptosis caused by amyloid-beta (Aß) overproduction is one of the most important pathological features in Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress induced by Aß overload plays a critical role in this process. Bis(ethylmaltolato)oxidovanadium (IV) (BEOV), a vanadium compound which had been regarded as peroxisome proliferator-activated receptor γ (PPARγ) agonist, was reported to exert an antagonistic effect on ER stress. In this study, we tested whether BEOV could ameliorate the Aß-induced neuronal apoptosis by inhibiting ER stress. It was observed that BEOV treatment ameliorated both tunicamycin-induced and/or Aß-induced ER stress and neurotoxicity in a dose-dependent manner through downgrading ER stress-associated and apoptosis-associated proteins in primary hippocampal neurons. Consistent with in vitro results, BEOV also reduced ER stress and inhibited neuronal apoptosis in hippocampi and cortexes of transgenic AD model mice. Moreover, by adopting GW9662 and salubrinal, the inhibitor of PPARγ and hyperphosphorylated eukaryotic translation initiation factor 2α, respectively, we further confirmed that BEOV alleviated Aß-induced ER stress and neuronal apoptosis in primary hippocampal neurons by activating PPARγ. Taken together, these results provided scientific evidences to support the concept that BEOV ameliorates Aß-induced ER stress and neuronal apoptosis through activating PPARγ.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hipocampo/metabolismo , Neurônios/metabolismo , PPAR gama/metabolismo , Vanadatos/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Animais , Apoptose/genética , Estresse do Retículo Endoplasmático/genética , Hipocampo/patologia , Camundongos , Camundongos Transgênicos , Neurônios/patologia , PPAR gama/genéticaRESUMO
AIM: To study the appearances of acute interstitial edematous pancreatitis (IEP) on non-enhanced MR imaging. METHODS: A total of 53 patients with IEP diagnosed by clinical features and laboratory findings were underwent MR imaging. MR imaging sequences included fast spoiled gradient echo (FSPGR) fat saturation axial T1-weighted imaging, gradient echo T1-weighted (in phase), single shot fast spin echo (SSFSE) T2-weighted, respiratory triggered (R-T) T2-weighted with fat saturation, and MR cholangiopancreatography. Using the MR severity score index, pancreatitis was graded as mild (0-2 points), moderate (3-6 points) and severe (7-10 points). RESULTS: Among the 53 patients, IEP was graded as mild in 37 patients and as moderate in 16 patients. Forty-seven of 53 (89%) patients had at least one abnormality on MR images. Pancreas was hypointense relative to liver on FSPGR T1-weighted images in 18.9% of patients, and hyperintense in 25% and 30% on SSFSE T2-weighted and R-T T2-weighted images, respectively. The prevalences of the findings of IEP on R-T T2-weighted images were, respectively, 85% for pancreatic fascial plane, 77% for left renal fascial plane, 55% for peripancreatic fat stranding, 42% for right renal fascial plane, 45% for perivascular fluid, 40% for thickened pancreatic lobular septum and 25% for peripancreatic fluid, which were markedly higher than those on in-phase or SSFSE T2-weighted images (P<0.001). CONCLUSION: IEP primarily manifests on non-enhanced MR images as thickened pancreatic fascial plane, left renal fascial plane, peripancreatic fat stranding, and peripancreatic fluid. R-T T2-weighted imaging is more sensitive than in-phase and SSFSE T2-weighted imaging for depicting IEP.
Assuntos
Edema/patologia , Imageamento por Ressonância Magnética/métodos , Pancreatite/patologia , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Many studies have shown that imbalance of mineral metabolism may play an important role in Alzheimer's disease (AD) progression. It was recently reported that selenium could reverse memory deficits in AD mouse model. We carried out multi-time-point ionome analysis to investigate the interactions among 15 elements in the brain by using a triple-transgenic mouse model of AD with/without high-dose sodium selenate supplementation. Except selenium, the majority of significantly changed elements showed a reduced level after 6-month selenate supplementation, especially iron whose levels were completely reversed to normal state at almost all examined time points. We then built the elemental correlation network for each time point. Significant and specific elemental correlations and correlation changes were identified, implying a highly complex and dynamic crosstalk between selenium and other elements during long-term supplementation with selenate. Finally, we measured the activities of two important anti-oxidative selenoenzymes, glutathione peroxidase and thioredoxin reductase, and found that they were remarkably increased in the cerebrum of selenate-treated mice, suggesting that selenoenzyme-mediated protection against oxidative stress might also be involved in the therapeutic effect of selenate in AD. Overall, this study should contribute to our understanding of the mechanism related to the potential use of selenate in AD treatment.
Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Íons/análise , Minerais/análise , Ácido Selênico/administração & dosagem , Animais , Antioxidantes/análise , Modelos Animais de Doenças , Glutationa Peroxidase/análise , Camundongos Transgênicos , Tiorredoxina Dissulfeto Redutase/análiseRESUMO
Computed tomography (CT) and magnetic resonance imaging (MRI) are excellent modalities which have the ability to detect, depict and stage the nerve invasion associated with pancreatic carcinoma. The aim of this article is to review the CT and MR patterns of pancreatic carcinoma invading the extrapancreatic neural plexus and thus provide useful information which could help the choice of treatment methods. Pancreatic carcinoma is a common malignant neoplasm with a high mortality rate. There are many factors influencing the prognosis and treatment options for those patients suffering from pancreatic carcinoma, such as lymphatic metastasis, adjacent organs or tissue invasion, etc. Among these factors, extrapancreatic neural plexus invasion is recognized as an important factor when considering the management of the patients.
RESUMO
Pancreatic carcinoma is an extremely high-grade malignant tumor with fast development and high mortality. The incidence of pancreatic carcinoma continues to increase. Peripancreatic invasion and metastasis are the main characteristics and important prognostic factors in pancreatic carcinoma, especially invasion into the nervous system; pancreatic nerve innervation includes the intrapancreatic and extrapancreatic nerves. A strong grasp of pancreatic nerve innervation may contribute to our understanding of pancreatic pain modalities and the metastatic routes for pancreatic carcinomas. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful techniques for depicting the anatomy of extrapancreatic nerve innervation. The purpose of the present work is to show and describe the anatomy of the extrapancreatic neural plexus and to elucidate its characteristics using CT and MRI, drawing on our own previous work and the research findings of others.
RESUMO
This study characterized the concentration-time profile of melamine in the heart, liver, spleen, lungs, kidneys, bladder, feces, urine, and plasma after melamine (MM) administration. Female Sprague-Dawley rats received a single oral dose of 1.0 g/kg body weight. Samples (n=4 per time point) were collected at 12, 24, 48, 72, 96, 120, 144, and 168 h. Based on calculations of the area under the concentration-time curves after dosing, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) was used to detect MM concentration in tissues. Peak concentrations of MM are reached in the livers and lungs at 12 h after dosing and in hearts, spleens, kidneys, bladders, feces, urine, and plasma at 24 h after dosing. More than 90% of the ingested MM is excreted in feces and urine within 24 h. These results provided initial understanding of the tissue disposition of MM. Moreover, this study demonstrates that UPLC-MS-MS can be used to detect MM in biological samples.
Assuntos
Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Triazinas/farmacocinética , Administração Oral , Animais , Fezes/química , Feminino , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Baço/metabolismo , Distribuição Tecidual , Triazinas/administração & dosagem , Triazinas/sangue , Triazinas/urina , Bexiga Urinária/metabolismoRESUMO
A high performance gas chromatography-mass spectrometry (GC-MS) method for the determination of 25 organochlorine pesticides in tea has been developed. The samples of tea were extracted with n-hexane-acetone (2: 1, v/v). The extract was purified by using a Florisil column with n-hexane-ethyl acetate (9: 1, v/v) as elution solvent. Chromatographic analysis was performed on a DB-35MS capillary column. Satisfactory separation and sensitivity of 25 organochlorine pesticides were obtained with the proposed method. The analytical results show the working curves for 25 organochlorine pesticides were linear in the range of 0.010 - 0.500 mg/L by GC-MS on selective ion monitoring mode. The recoveries of 25 organochlorine pesticides at spiked levels of 0.01 -0.20 mg/kg were 70.8% - 105.5%, and relative standard deviations (RSDs) were 1.6% - 12.7%. The limits of quantitation were 0.01 mg/kg except that for endosulfan I and endosulfan II that were 0.02 mg/kg.