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OBJECTIVES: Diabetes is closely linked to hearing loss, yet the exact mechanisms remain unclear. Cochlear stria vascularis and pericytes (PCs) are crucial for hearing. This study investigates whether high glucose induces apoptosis in the cochlear stria vascularis and pericytes via elevated ROS levels due to oxidative stress, impacting hearing loss. METHODS: We established a type II diabetes model in C57BL/6J mice and used auditory brainstem response (ABR), Evans blue staining, HE staining, immunohistochemistry, and immunofluorescence to observe changes in hearing, blood-labyrinth barrier (BLB) permeability, stria vascularis morphology, and apoptosis protein expression. Primary cultured stria vascularis pericytes were subjected to high glucose, and apoptosis levels were assessed using flow cytometry, Annexin V-FITC, Hoechst 33342 staining, Western blot, Mitosox, and JC-1 probes. RESULTS: Diabetic mice showed decreased hearing thresholds, reduced stria vascularis density, increased oxidative stress, cell apoptosis, and decreased antioxidant levels. High glucose exposure increased apoptosis and ROS content in pericytes, while mitochondrial membrane potential decreased, with AIF and cytochrome C (CytC) released from mitochondria to the cytoplasm. Adding oxidative scavengers reduced AIF and CytC release, decreasing pericyte apoptosis. DISCUSSION: Hyperglycemia may induce mitochondrial apoptosis of cochlear stria vascularis pericytes through oxidative stress.
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Fator de Indução de Apoptose , Apoptose , Citocromos c , Hiperglicemia , Camundongos Endogâmicos C57BL , Mitocôndrias , Estresse Oxidativo , Pericitos , Proteínas Proto-Oncogênicas c-bcl-2 , Espécies Reativas de Oxigênio , Estria Vascular , Animais , Pericitos/metabolismo , Pericitos/efeitos dos fármacos , Pericitos/patologia , Estria Vascular/metabolismo , Estria Vascular/patologia , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Citocromos c/metabolismo , Fator de Indução de Apoptose/metabolismo , Hiperglicemia/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Masculino , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Cóclea/metabolismo , Cóclea/patologiaRESUMO
INTRODUCTION: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. METHODS: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. RESULTS: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. CONCLUSIONS: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. TRIAL REGISTRATION: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).
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Coal dust (CD) is a common pollutant, and epidemiological surveys indicate that long-term exposure to coal dust not only leads to the occurrence of pulmonary diseases but also has certain impacts on cognitive abilities. However, there is little open-published literature on the effects and specific mechanisms of coal dust exposure on the cognition of patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). An animal model has been built in this study with clinical population samples to explore the changes in neuroinflammation and cognitive abilities with coal dust exposure. In the animal model, compared to C57BL/6 mice, APP/PS1 mice exposed to coal dust exhibited more severe cognitive impairment, accompanied by significantly elevated levels of neuroinflammatory factors Apolipoprotein E4 (AOPE4) and Interleukin-6 (IL6) in the hippocampus, and more severe neuronal damage. In clinical sample sequencing, it was found that there is significant upregulation of AOPE4, neutrophils, and IL6 expression in the peripheral blood of MCI patients compared to normal individuals. Mechanistically, cell experiments revealed that IL6 could promote the phosphorylation of ERK1/2 and enhance the expression of transcription factor SP1, thereby promoting AOPE4 expression. The results of this study suggest that coal dust can promote the upregulation of IL6 and AOPE4 in patients, exacerbating cognitive impairment.
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Carvão Mineral , Disfunção Cognitiva , Poeira , Interleucina-6 , Camundongos Endogâmicos C57BL , Disfunção Cognitiva/induzido quimicamente , Animais , Camundongos , Interleucina-6/metabolismo , Sistema de Sinalização das MAP Quinases , Fator de Transcrição Sp1/metabolismo , Humanos , Transdução de Sinais , Doença de Alzheimer , MasculinoRESUMO
Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc. Oxidative stress levels, mitochondrial function and endothelial barrier changes were observed in vitro by using DCFH-DA probe detection, flow cytometry, JC-1 probe, immunofluorescence and the establishment in vitro BLB models, etc. QU pretreatment activates the PI3K/AKT signaling pathway, inhibits CDDP-induced oxidative stress, protects mitochondrial function, and reduces mitochondrial apoptosis in PCs. However, PI3K/AKT specific inhibitor (LY294002) partially reverses the protective effects of QU. In addition, in vitro BLB models were established by coculturing PCs and endothelial cells (ECs), which suggests that QU both reduces the CDDP-induced apoptosis in PCs and improves the endothelial barrier permeability. On the whole, the research findings suggest that QU can be used as a novel treatment to reduce CDDP-induced ototoxicity.
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Cisplatino , Ototoxicidade , Camundongos , Animais , Masculino , Cisplatino/farmacologia , Cisplatino/metabolismo , Pericitos/metabolismo , Quercetina/farmacologia , Quercetina/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células Endoteliais/metabolismo , Ototoxicidade/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo , ApoptoseRESUMO
BACKGROUND: Noise is an important environmental stressor in the industrialized world and has received increasing attention in recent years. Although epidemiological research has extensively demonstrated the relationship between noise and cognitive impairment, the specific molecular mechanisms and targets remain to be fully explored and understood. METHODS: To address this issue, 5-month-old C57BL/6 mice were divided into two groups, with one group exposed to white noise at 98 dB. The effects of noise on cognition in mice were investigated through molecular biology and behavioral experiments. Subsequently, transcriptomic sequencing of the hippocampus in both groups of mice was performed and enrichment analysis of differentially expressed genes (DEGs) was conducted using KEGG and GO databases. Furthermore, LASSO analysis was used to further narrow down the relevant DEGs, followed by enrichment analysis of these genes using KEGG and GO databases. The DEGs were further validated by rt-qPCR. RESULTS: Following noise exposure, the hippocampus levels of inflammation-related factors increased, the phosphorylation of Tau protein increased, the postsynaptic density protein decreased, the number of Nissl bodies decreased, and cell shrinkage in the hippocampus increased. Moreover, the behavioral experiments manifest characteristics indicative of a decline in cognitive.A total of 472 DEGs were identified through transcriptomic analysis, and seven relevant genes were screened by the LASSO algorithm, which were further validated by PCR to confirm their consistency with the omics results. CONCLUSION: In conclusion, noise exposure affects cognitive function in mice through multiple pathways, and the omics results provide new evidence for the cognitive impairment induced by noise exposure.
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Disfunção Cognitiva , Perfilação da Expressão Gênica , Camundongos , Animais , Camundongos Endogâmicos C57BL , Hipocampo/metabolismo , CogniçãoRESUMO
OBJECTIVE: The study aimed to observe the effects of noise exposure on the pericytes of the cochlear stria vascularis (SV) in mice and to investigate its molecular mechanism. METHOD: Male C57BL/6J mice aged 6-8 weeks were used as the subjects. Auditory Brainstem Response (ABR) was used to assess hearing loss. Hematoxylin and Eosin (HE) staining was conducted to observe morphological alterations in the SV. Immunofluorescence combined with transmission electron microscopy (TEM) was used to scrutinize changes in pericytes following acoustic injury. Western blotting (WB) was used to assess the expression variations of the migration-related protein Osteopontin (OPN). Evans Blue assay was performed to evaluate the permeability of the blood labyrinth barrier (BLB). 4-Hydroxynonenal (4-HNE) staining, in conjunction with measurements of Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Catalase (CAT) content, was used to ascertain whether oxidative stress injury occurred in the SV. WB, combined with immunofluorescence, was used to examine alterations in the expression of proliferator-activated receptor-gamma coactivator 1α (PGC-1α) in the SV and pericytes. RESULTS: Noise exposure resulted in permanent hearing loss in C57BL/6J mice, accompanied by SV swelling, migration of pericytes from their vascular attachments, BLB leakage, elevated oxidative stress levels in the SV, and reduced expression of PGC-1α on both the SV and migrating pericytes. CONCLUSION: Noise exposure may potentially increase oxidative stress levels in the SV, downregulate the expression levels of PGC-1α, promote pericytes migration, and subsequently lead to an elevation in BLB permeability.
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Surdez , Orelha Interna , Perda Auditiva Provocada por Ruído , Animais , Humanos , Masculino , Camundongos , Cóclea/metabolismo , Surdez/metabolismo , Orelha Interna/metabolismo , Perda Auditiva Provocada por Ruído/metabolismo , Camundongos Endogâmicos C57BL , Pericitos/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoRESUMO
In recent years, it has become an acknowledged fact that noise exposure can lead to cognitive impairments, and researchers have shown increasing interest in this area. However, the detrimental impact of noise exposure on Alzheimer's disease (AD) animal models might be considerably greater than on ordinary model mice, yet the mechanisms by which noise exposure affects the hippocampus in these models have been scarcely investigated. This study we used 4D Label-free proteomics to identify distinctive differentially expressed proteins in the hippocampus of AD model mice following noise exposure. Among these proteins, the presence of Cathepsin S(CTSS) cannot be disregarded. Utilizing experimental techniques such as Western blot, immunofluorescence, and rt-qPCR, we confirmed the expression of CTSS in the hippocampus of APP/PS1 mice after noise exposure. Additionally, we examined downstream molecules including P53,BCL-2, BAX, and CASPASE3 using KEGG pathway analysis. The results indicated an elevation in CTSS expression, a reduction in the anti-apoptotic gene BCL-2, and an increase in the expression of BAX and cleaved CASPASE3. Based on these findings, we hypothesize that noise exposure potentially heightens apoptosis within the hippocampus through upregulating CTSS expression, subsequently posing a threat to AD model animals.
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Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Hipocampo/metabolismo , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Camundongos Transgênicos , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/metabolismoRESUMO
Starch-fatty acid complexes used as emulsifiers have caught great attention because of their renewability and excellent emulsifying property, the development of a simple and efficient synthesis method for the fabrication of starch-fatty acid complexes is still greatly challenging. Herein, the rice starch-fatty acid complexes (NRS-FA) were successfully prepared by mechanical activation method using different long chain fatty acids (myristic acid, palmitic acid, and stearic acid) and native rice starch (NRS) as the raw materials. The results showed that the prepared NRS-FA with a V-shaped crystalline structure exhibited a higher digestion resistance than NRS. Moreover, when the chain length of fatty acids increased from 14 to 18 carbons, the contact angle of the complexes was much closer to 90°, and the average particle size was smaller, deriving the better emulsifying property of NRS-FA18 complexes, which were suitable to be used as an emulsifier to stabilize curcumin-loaded Pickering emulsions. The results of storage stability and in vitro digestion showed that the curcumin retention could reach 79.4 % after 28 days of storage and 80.8 % of curcumin was retained in the system after simulated gastric digestion, showing good encapsulation and delivery performance of prepared Pickering emulsions, which attributed to the enhancement of the coverage of particles at the oil-water interface.
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Curcumina , Amido , Emulsões/química , Amido/química , Curcumina/química , Ácidos Graxos , Técnicas de Síntese em Fase Sólida , Emulsificantes/químicaRESUMO
BACKGROUND: Bleeding episodes in hemophiliacs with inhibitors are difficult to control. Staidson protein-0601 (STSP-0601), a specific factor (F)X activator purified from the venom of Daboia russelii siamensis, has been developed. OBJECTIVES: We aimed to investigate the efficacy and safety of STSP-0601 in preclinical and clinical studies. METHODS: In vitro and in vivo preclinical studies were performed. A phase 1, first-in-human, multicenter, and open-label trial was conducted. The clinical study was divided into parts A and B. Hemophiliacs with inhibitors were eligible for this study. Patients received a single intravenous injection of STSP-0601 (0.01 U/kg, 0.04 U/kg, 0.08 U/kg, 0.16 U/kg, 0.32 U/kg, or 0.48 U/kg) in part A or a maximum of 6 4-hourly injections (0.16 U/kg) in part B. The primary endpoint for each part was the number of adverse events (AEs) from baseline to 168 hours after administration. This study was registered at clinicaltrials.gov (NCT-04747964 and NCT-05027230). RESULTS: Preclinical studies showed that STSP-0601 could specifically activate FX in a dose-dependent manner. In the clinical study, 16 patients in part A and 7 patients in part B were enrolled. Eight (22.2%) AEs in part A and 18 (75.0%) AEs in part B were reported to be related to STSP-0601. Neither severe AEs nor dose-limiting toxicity events were reported. There were no thromboembolic event. The antidrug antibody of STSP-0601 was not detected. CONCLUSION: Preclinical and clinical studies showed that STSP-0601 had a good ability to activate FX and had a good safety profile. STSP-0601 could be used as a hemostatic treatment in hemophiliacs with inhibitors.
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Hemofilia A , Humanos , Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Proteínas de Neoplasias , Cisteína Endopeptidases , AnticorposRESUMO
The hippocampus is highly plastic and vulnerable to hypoxia. However, it is unknown whether and how it adapts to chronic hypobaric hypoxia in humans. With a unique sample of Tibetans and acclimatized Han Chinese individuals residing on the Tibetan plateau, we aimed to build a neuroanatomic profile of the altitude-adapted hippocampus by measuring the volumetric differences in the whole hippocampus and its subfields. High-resolution T1-weighted magnetic resonance imaging was performed in healthy Tibetans (TH, n = 72) and healthy Han Chinese individuals living at an altitude of more than 3,500 m (HH, n = 27). In addition, healthy Han Chinese individuals living on a plain (HP, n = 72) were recruited as a sea-level reference group. Whereas the total hippocampal volume did not show a significant difference across groups when corrected for age, sex, and total intracranial volume, subfield-level differences within the hippocampus were found. Post hoc analyses revealed that Tibetans had larger core hippocampal subfields (bilateral CA3, right CA4, right dentate gyrus); a larger right hippocampus-amygdala transition area; and smaller bilateral presubiculum, right subiculum, and bilateral fimbria, than Han Chinese subjects (HH and/or HP). The hippocampus and all its subfields were found to be slightly and non-significantly smaller in HH subjects than in HP subjects. As a primary explorational study, our data suggested that while the overall hippocampal volume did not change, the core hippocampus of Tibetans may have an effect of adaptation to chronic hypobaric hypoxia. However, this adaptation may have required generations rather than mere decades to accumulate in the population.
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Improving standards of living have resulted in an increased focus on health and image management. In a context where the quality of healthcare information is unguaranteed, the adoption behavior intention of online health information varies greatly. Hence, it is essential to take effective measures to guide community users to obtain high-quality information on demand. From the perspective of personality traits, the present study analyzed the influencing factors and mechanisms of adoption behavior intention of healthcare information in online healthcare communities as well as the moderating effects of social support. A quantitative analysis of 380 respondents revealed positive associations between five personality dimensions and the adoption behavior intention of healthcare information-extraversion, agreeableness, conscientiousness, neuroticism, and openness. The study also determined that health concerns and health-related self-efficacy played a mediating role across various degrees between the conscientiousness and adoption behavior intention of healthcare information. As an important contextual factor influencing health outcomes, social support is common in online healthcare communities. The study examined the effect of the interaction between inner traits and social support on adoption behavior intention. Perceived self-esteem support strengthened the indirect effect of conscientiousness on adoption behavior intention mediated by health concerns and health-related self-efficacy. Additionally, the impact of high neuroticism interacted with low levels of perceived self-esteem support on adoption behavior intention was significant. Likewise, emotional supportive information did not help in facilitating the adoption behavior intention in terms of all five personality traits and negatively influence the adoption behavior intention for individuals high in neuroticism and agreeableness. The possible explanation for the results was discussed with the intention of understanding the psychological mechanisms which guide adoption behavior intention.
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Hyperglycemia-induced neuronal endoplasmic reticulum (ER) stress is particularly important for the pathogenesis of diabetic encephalopathy. Spermidine (Spd) has neuroprotection in several nervous system diseases. Our current study to explore the potential protective role of Spd in hyperglycemia-induced neuronal ER stress and the underlying mechanisms. HT22 cells were treated with high glucose (HG) to establish an in-vitro model of hyperglycemia toxicity. The HT22 cells' activity was tested by cell counting kit-8 assay. RNA interference technology was used to silence the expression of growth differentiation factor 11 (GDF11) in HT22 cells. The GDF11 expression levels of mRNA were assessed using reverse transcription-PCR (RT-PCR). Western blotting analysis was applied to evaluate the expressions of GRP78 and cleaved caspase-12. Spd markedly abolished HG-exerted decline in cell viability as well as upregulations of GRP78 and cleaved caspase-12 in HT22 cells, indicating the protection of Spd against HG-induced neurotoxicity and ER stress. Furthermore, we showed that Spd upregulated the expression of GDF11 in HG-exposed HT22 cells. While, silenced GDF11 expression by RNA interference reversed the protective effects of Spd on HG-elicited neurotoxicity and ER stress in HT22 cells. These results indicated that Spd prevents HG-induced neurotoxicity and ER stress through upregulation of GDF11. Our findings identify Spd as a potential treatment for diabetic encephalopathy as well as ER stress-related neurologic diseases.
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Encefalopatias , Hiperglicemia , Humanos , Estresse do Retículo Endoplasmático , Espermidina/farmacologia , Regulação para Cima , Caspase 12/metabolismo , Apoptose , Glucose/metabolismo , Fatores de Diferenciação de Crescimento/metabolismo , Fatores de Diferenciação de Crescimento/farmacologia , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/farmacologiaRESUMO
The molecular targets and mechanisms of propolis ameliorating metabolic syndrome are not fully understood. Here, we report that Brazilian green propolis reduces fasting blood glucose levels in obese mice by disrupting the formation of CREB/CRTC2 transcriptional complex, a key regulator of hepatic gluconeogenesis. Using a mammalian two-hybrid system based on CREB-CRTC2, we identify artepillin C (APC) from propolis as an inhibitor of CREB-CRTC2 interaction. Without apparent toxicity, APC protects mice from high fat diet-induced obesity, decreases fasting glucose levels, enhances insulin sensitivity and reduces lipid levels in the serum and liver by suppressing CREB/CRTC2-mediated both gluconeogenic and SREBP transcriptions. To develop more potential drugs from APC, we designed and found a novel compound, A57 that exhibits higher inhibitory activity on CREB-CRTC2 association and better capability of improving insulin sensitivity in obese animals, as compared with APC. In this work, our results indicate that CREB/CRTC2 is a suitable target for developing anti-metabolic syndrome drugs.
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Proteína de Ligação a CREB/metabolismo , Sistemas de Liberação de Medicamentos , Síndrome Metabólica/metabolismo , Camundongos Obesos/metabolismo , Própole/metabolismo , Fatores de Transcrição/metabolismo , Animais , Glicemia , Brasil , Proteína de Ligação a CREB/genética , Desenvolvimento de Medicamentos , Descoberta de Drogas , Gluconeogênese , Resistência à Insulina , Fígado/metabolismo , Síndrome Metabólica/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Obesos/genética , Obesidade/metabolismo , Própole/genética , Fatores de Transcrição/genéticaRESUMO
Vibrio parahaemolyticus is recognized as one of the most important foodborne pathogens responsible for gastroenteritis in humans. The blaCARB-17 gene is an intrinsic ß-lactamase gene and a novel species-specific genetic marker of V. parahaemolyticus. In this study, a loop-mediated isothermal amplification (LAMP) assay combined with a lateral flow dipstick (LFD) was developed targeting this blaCARB-17 gene. The specificity of LAMP-LFD was ascertained by detecting V. parahaemolyticus ATCC 17802 and seven other non-V. parahaemolyticus strains. Finally, the practicability of LAMP-LFD was confirmed by detection with V. parahaemolyticus-contaminated samples and natural food samples. The results showed that the optimized reaction parameters of LAMP are as follows: 2.4 mmol/l Mg2+, 0.96 mmol/l dNTPs, 4.8 U Bst DNA polymerase, and an 8:1 ratio of inner primer to outer primer, at 63°C for 40 min. The optimized reaction time of the LFD assay is 60 min. Cross-reactivity analysis with the seven non-V. parahaemolyticus strains showed that LAMP-LFD was exclusively specific for V. parahaemolyticus. The detection limit of LAMP-LFD for V. parahaemolyticus genomic DNA was 2.1 × 10-4 ng/µl, corresponding to 630 fg/reaction and displaying a sensitivity that is 100-fold higher than that of conventional PCR. LAMP-LFD in a spiking study revealed a detection limit of approximately 6 CFU/ml, which was similar with conventional PCR. The developed LAMP-LFD specifically identified the 10 V. parahaemolyticus isolates from 30 seafood samples, suggesting that this LAMP-LFD may be a suitable diagnostic method for detecting V. parahaemolyticus in aquatic foods.
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Microbiologia de Alimentos/métodos , Alimentos Marinhos/microbiologia , Vibrio parahaemolyticus/isolamento & purificação , beta-Lactamases/genética , DNA Bacteriano/genética , Genoma Bacteriano/genética , Limite de Detecção , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Vibrio parahaemolyticus/genéticaRESUMO
This study focused on constructing a high-solid reaction system to prepare type 3 resistant starch (RS3) with high-amylose maize starch as raw material by mechanical activation (MA) pretreatment combined with thermal and freeze-thaw treatments. MA pretreatment effectively destroyed the crystal structure and molecular structure of native starch. MA damaged starch with a certain viscosity could form dough with a small amount of water to construct a starch continuous phase system. RS content increased with the damage levels of starch as the formation of double helix structure, attributed to that the molecules of MA damaged starch could be easy to move and form recrystallization structure. Thermal and freeze-thaw treatments contributed to strong interaction of starch-water and the re-formation of internal crystal structure of MA damaged starch to form RS3. This study provides insight into the development of a highly effective approach for large scale production of resistant starch.
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Amilose , Zea mays , Amido Resistente , Amido , ViscosidadeRESUMO
This study proposed an integrated technique of reduction coupled with an oxidation process in order to acquire simultaneously both decolorization and mineralization of orange II under the condition of microwave-assisted milling. Experimental variables of initial dye concentration, iron dosage, microwave power, solution pH and initial H2O2 concentration were systematically studied. Under the optimal operational parameters (100 mg/L aqueous solution of pH 3 containing 400 mg/L H2O2 while controlling microwave power at 400 W), the results showed that the decolorization efficiency is up to 91% after reaction for 2 min and the total organic carbon removal efficiencies were 72.7% and 80.5% at a reaction time of 10 min and 60 min, respectively. It indicated that the decolorization and mineralization of orange II were largely enhanced by the reduction of zero-valent iron in the ball milling process and the oxidation of hydroxyl radicals generated by hydrogen peroxide. It suggested that microwave-assisted ball milling technology has potential application for degradation of azo dye in wastewater.
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Compostos Azo/química , Benzenossulfonatos/química , Micro-Ondas , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Peróxido de Hidrogênio/química , OxirreduçãoRESUMO
In this study, the effect factors and mechanisms of doxycycline hydrochloride (DOX) adsorption on copper nitrate modified biochar (Cu-BC) was investigated. Cu-BC absorbent was synthesized through calcination of peanut shells biomass at 450°C and then impregnation with copper nitrate. The Cu-BC has exhibited excellent sorption efficiency about 93.22% of doxycycline hydrochloride from aqueous solution, which was double higher than that of the unmodified biochar. The experimental results suggest that the adsorption efficiency of DOX on the Cu-BC is dominated by the strong complexation, electrostatic interactions between DOX molecules and the Cu-BC samples. Comprehensively considering the cost, efficiency and the application to realistic water, the Cu-BC hold the significant potential for enhancing the effectiveness to remove DOX from water.
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Carvão Vegetal/química , Cobre/química , Doxiciclina/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Adsorção , ÁguaRESUMO
AIMS/HYPOTHESIS: As one of the key adipokines, retinol binding protein 4 (RBP4) is suggested to positively correlate with insulin resistance; however, not all clinical studies support this association. Although some explanations are proposed for this discrepancy, the temporal aspect of RBP4 secretion has not been considered. Aryl hydrocarbon receptor nuclear translocator-like (also known as BMAL1) and its target D site-binding protein (DBP) are both pivotal transcription factors of the circadian core clock. Given the overwhelming presence of circadian control in metabolism and the principal role of the liver in RBP4 secretion, we hypothesised that RBP4 may oscillate under the control of BMAL1 and act as a hepatokine, participating in the maintenance of glucose homeostasis by the circadian clock. METHODS: We used liver-specific Bmal1 (also known as Arntl)-knockout mice and recombinant adenoviruses expressing short-hairpin RNA (shRNA) specific for Dbp or Rbp4 in the liver. RESULTS: RBP4 displayed diurnal oscillations in the liver and plasma, which were dampened in liver-specific-Bmal1-knockout mice. BMAL1 regulated hepatic RBP4 expression via its direct target, DBP. Hepatic knockdown of RBP4 or DBP increased whole-body insulin sensitivity in mice in a time-of-day-dependent manner. Conversely, hepatic overexpression of RBP4 reversed the insulin-sensitising effects of liver-specific depletion of BMAL1. CONCLUSIONS/INTERPRETATION: Our results not only provide a novel mechanism for circadian regulation of RBP4, but also unveil a critical role of RBP4, acting as a hepatokine in the regulation of glucose metabolism by the circadian clock.
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Metabolismo dos Carboidratos/genética , Relógios Circadianos/fisiologia , Citocinas , Hepatócitos/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/fisiologia , Animais , Células Cultivadas , Relógios Circadianos/genética , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Citocinas/genética , Citocinas/fisiologia , Regulação da Expressão Gênica , Células HEK293 , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células NIH 3T3 , Proteínas Plasmáticas de Ligação ao Retinol/genéticaRESUMO
Endometriosis is a common mysterious and fascinating gynaecological condition with diverse clinical manifestations, highly variable and unpredictable clinical course with decreased quality of life. Clinically, Salvia miltiorrhiza Bunge (SMB, Chinese Danshen) has been applied to treat endometriosis and get satisfactory results. The present study was aimed to explore the effects of the extracts of SMB (ESMB) on the serum levels of cancer antigen 125 (CA-125) and the levels of interleukin (IL)-13, IL-18 and tumor necrosis factor-alpha (TNF-alpha) in the peritoneal fluids of rat endometriosis models. Three extraction methods for SMB were compared, which are the sample extracted with conventional method, the sample extracted with espresso coffee machine and the commercial condensed powder of natural products. We determined tanshinone IIA, salvianolic acid B and danshensu in the ESMB of different extraction methods. Forty female Sprague-Dawley (SD) rats were randomly divided into ESMB group, Danazol (positive control) group, model group and the sham-operation group (Sham group). After all the treatment ended, the serum levels of CA125 and the levels of IL-13, IL-18 and TNF-alpha in the peritoneal fluids of rat endometriosis models were measured using enzyme-linked immune-sorbent assay (ELISA) as directed by the manufacturer. The extraction efficiency of the ESMB samples extracted with coffee machine ranged from 600µm to 710µm was the highest. The serum levels of CA-125 and the levels of IL-18 and TNF-alpha in the peritoneal fluids of ESMB group, Danazol group and Sham group were significantly lower than those of the Model group (P<0.05). The serum levels of CA-125 and the levels of IL-18 and TNF-alpha in the peritoneal fluids of Danazol group and ESMB group were significantly higher than those of Sham group, respectively (P<0.05), and no marked difference existed between them (P>0.05). The levels of IL-13 in the peritoneal fluids of ESMB group, Danazol group and Sham group were significantly higher than those of the Model group (P<0.05). The levels of IL-13 in the peritoneal fluids of ESMB group and Danazol group were significantly lower than those of Sham group (P<0.05), and there was no marked difference between ESMB group and Sham group (P>0.05). ESMB shows promises in treating endometriosis by markedly decreasing the serum levels of CA-125 and the levels of IL-18 and TNF-alpha in the peritoneal fluids and significantly increasing the levels of IL-13 in the peritoneal fluids.
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Líquido Ascítico/metabolismo , Antígeno Ca-125/metabolismo , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Endometriose/tratamento farmacológico , Fitoterapia , Salvia miltiorrhiza , Animais , Antígeno Ca-125/sangue , Citocinas/sangue , Danazol/farmacologia , Danazol/uso terapêutico , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Antagonistas de Estrogênios/farmacologia , Antagonistas de Estrogênios/uso terapêutico , Feminino , Interleucina-13/sangue , Interleucina-13/metabolismo , Interleucina-18/sangue , Interleucina-18/metabolismo , Cavidade Peritoneal/patologia , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Prostatodynia remains a difficult clinical problem. Resiniferatoxin (RTX), an ultrapotent vanilloid, can produce a selective and long-lasting desensitization of nociception via C-fiber sensory neurons. Substance P (SP) and calcitonin gene-related peptide (CGRP) released from C-fibers are key neurotransmitters in visceral pain. In this study, we evaluated the analgesic effect of intrathecal RTX on rat prostatodynia. METHODS: Male Sprague-Dawley rats were divided into 3 groups for different treatment. In group A, sham operation was preformed. In group B, 100 microl complete Freund's adjuvant (CFA) was injected into the rat's bilateral ventral prostate to induce chronic inflammation. In group C, after prostatitis formed, 50 microl 10 nmol/L RTX was injected into the rat's lumbosacral (L5-S2) vertebral canal. SP and CGRP contents in the spinal cord were investigated by immunohistochemistry and radioimmunoassay (RIA). Their transcriptional levels in dorsal root ganglion (DRG) were determined by reverse transcriptase polymerase chain reaction (RT-PCR). In addition, pelvic nerve afferent discharge was recorded to explore the neuro-electrophysiological mechanisms underlying RTX-induced effect. RESULTS: SP and CGRP released in the spinal cord and their synthesis in DRG were increased significantly in response to CFA-induced chronic prostatitis, whereas this increase was effectively inhibited by intrathecal RTX. Meanwhile, pelvic nerve afferent electrical activity was enhanced significantly in rats with chronic prostatitis, but it was attenuated markedly in RTX-treated rats paralleled by the change of neuropeptides. CONCLUSIONS: Intrathecal RTX administration could produce an analgesic effect on rat prostatodynia. Suppression of pelvic nerve afferent electrical activity may be a crucial mechanism underlying RTX-induced analgesia. RTX intrathecal application may present a novel analgesic strategy of prostatodynia.