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BACKGROUND: The disruption of blood-brain barrier (BBB), predominantly made up by brain microvascular endothelial cells (BMECs), is one of the characteristics of Alzheimer's disease (AD). Thus, improving BMEC function may be beneficial for AD treatment. Tanshinone IIA (Tan IIA) has been proved to ameliorate the cognitive dysfunction of AD. Herein, we explored how Tan IIA affected the function of BMECs in AD. METHODS: Aß1-42-treated brain-derived endothelium cells.3 (bEnd.3 cells) was employed for in vitro experiments. And we performed molecular docking and qPCR to determine the targeting molecule of Tan IIA on Sirtuins family. The APPswe/PSdE9 (APP/PS1) mice were applied to perform the in vivo experiments. Following the behavioral tests, protein expression was determined through western blot and immunofluorescence. The activities of oxidative stress-related enzymes were analyzed by biochemically kits. Nissl staining and thioflavin T staining were conducted to reflect the neurodegeneration and Aß deposition respectively. RESULTS: Molecular docking and qPCR results showed that Tan IIA mainly acted on Sirtuin1 (SIRT1) in Sirtuins family. The inhibitor of SIRT1 (EX527) was employed to further substantiate that Tan IIA could attenuate SIRT1-mediated endoplasmic reticulum stress (ER stress) in BMECs. Behavioral tests suggested that Tan IIA could improve the cognitive deficits in APP/PS1 mice. Tan IIA administration increased SIRT1 expression and alleviated ER stress in APP/PS1 mice. In addition, LRP1 expression was increased and RAGE expression was decreased after Tan IIA administration in both animals and cells. CONCLUSION: Tan IIA could promote Aß transportation by alleviating SIRT1-mediated ER stress in BMECs, which ameliorated cognitive deficits in APP/PS1 mice.
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Doença de Alzheimer , Células Endoteliais , Camundongos , Animais , Células Endoteliais/metabolismo , Sirtuína 1/metabolismo , Simulação de Acoplamento Molecular , Estresse do Retículo Endoplasmático , Doença de Alzheimer/tratamento farmacológico , Modelos Animais de DoençasRESUMO
Endocrine disrupting chemicals (EDCs) have been extensively explored due to their harmful effects on individual health and the environment by interfering with hormone activity and disrupting the endocrine system. However, their relationship with essential trace elements remains uncertain. This research aimed to investigate the possible correlation between essential trace elements and toxic metals, including cadmium (Cd), and lead (Pb) in children aged 1-5 years with various infectious diseases, including gastrointestinal disorders, typhoid fever, and pneumonia. The study was conducted on biological testing and specimen (scalp hair and whole blood) of diseased and non-diseased children of the same residential area and referent/control age-matched children from developed cities consuming domestically treated water. The media of biological samples were oxidized by an acid mixture before being analyzed by atomic absorption spectrophotometry. The accuracy and validity of the methodology were verified through accredited reference material from scalp hair and whole blood sample. The study results revealed that diseased children had lower mean values of essential trace elements (iron, copper, and zinc) in both scalp hair and blood, except for copper, which was found to be higher in blood samples of diseased children. This implies that the deficiency of essential residue and trace elements in children from rural areas who consume groundwater is linked to various infectious diseases. The study highlights the need for more human biomonitoring of EDCs to better comprehend their non-classical toxic properties and their concealed costs on human health. The findings suggest that exposure to EDCs could be associated with unfavorable health outcomes and emphasizes the need for future regulatory policies to minimize exposure and safeguard the health of current and forthcoming generations of children. Furthermore, the study highlights the implication of essential trace elements in maintaining good health and their potential correlation with toxic metals in the environment.
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Doenças Transmissíveis , Disruptores Endócrinos , Oligoelementos , Humanos , Criança , Oligoelementos/análise , Cobre , Zinco , Cádmio , Espectrofotometria AtômicaRESUMO
BACKGROUND: Rice is a crop that is very sensitive to low temperature, and its morphological development and production are greatly affected by low temperature. Therefore, understanding the genetic basis of cold tolerance in rice is of great significance for mining favorable genes and cultivating excellent rice varieties. However, there have been limited studies focusing on cold tolerance at the bud burst stage; therefore, considerable attention should be given to the genetic basis of cold tolerance at this stage. RESULTS: In this study, a natural population consisting of 211 rice landraces collected from 15 provinces in China and other countries was used for the first time to evaluate cold tolerance at the bud burst stage. Population structure analysis showed that this population was divided into two groups and was rich in genetic diversity. Our evaluation results confirmed that japonica rice was more tolerant to cold at the bud burst stage than indica rice. A genome-wide association study (GWAS) was performed with the phenotypic data of 211 rice landraces and a 36,727 SNP dataset under a mixed linear model. Twelve QTLs (P < 0.0001) were identified for the seedling survival rate (SR) after treatment at 4 °C, in which there were five QTLs (qSR2-2, qSR3-1, qSR3-2, qSR3-3 and qSR9) that were colocalized with those from previous studies and seven QTLs (qSR2-1, qSR3-4, qSR3-5, qSR3-6, qSR3-7, qSR4 and qSR7) that were reported for the first time. Among these QTLs, qSR9, harboring the most significant SNP, explained the most phenotypic variation. Through bioinformatics analysis, five genes (LOC_Os09g12440, LOC_Os09g12470, LOC_Os09g12520, LOC_Os09g12580 and LOC_Os09g12720) were identified as candidates for qSR9. CONCLUSION: This natural population consisting of 211 rice landraces combined with high-density SNPs will serve as a better choice for identifying rice QTLs/genes in the future, and the detected QTLs associated with cold tolerance at the bud burst stage in rice will be conducive to further mining favorable genes and breeding rice varieties under cold stress.
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Temperatura Baixa , Resposta ao Choque Frio/genética , Flores/crescimento & desenvolvimento , Flores/genética , Oryza/crescimento & desenvolvimento , Oryza/genética , Locos de Características Quantitativas/genética , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Estudo de Associação Genômica Ampla , GenótipoRESUMO
High-sensitivity and high-precision (2 SD ≤ 0.06) measurement of chromium (Cr) isotopes at the 10 ng level was successfully carried out using double spike multiple-collector inductively couple plasma mass spectrometry (MC-ICP-MS). To enhance the signal sensitivity and stability, the Aridus II desolvating nebulizer system was improved by placing its waste gas trap bottle in an ice chamber (5 °C cold trap). This setup, beyond Cr isotope analysis, can be applied to most heavy metal isotope measurements. The sensitivity of the 52Cr signal is ≥300 V mg-1 L (with a 1011Ω amplifier and a 110 µL min-1 uptake rate), an enhancement of ≥1.5 times compared to the Aridus II without the cold trap. In addition, the relative standard deviation of the 52Cr signal varied ≤4% over 8 h, demonstrating high stability. The δ53Cr values of common geological reference materials determined using 10 ng of Cr are in excellent agreement with results measured at 25 ng and 50 ng and are consistent with previous determinations, validating the accurate and precise Cr isotope ratio measurements. An empirical method is proposed to correct for the residual (after subtraction) effect of Fe interference on δ53Cr determination. This method relies on a linear relationship between the [Fe]/[Cr] and δ53Cr shift within one analytical session. Finally, we report the δ53Cr values of 19 new reference materials, ranging from -0.44 to 0.49. Among them, GSS-7 (-0.44 ± 0.02, 2 SD, n = 5), GSS-4 (0.48 ± 0.02, 2 SD, n = 5), and GSD-10 (0.49 ± 0.05, 2 SD, n = 5) can be used as candidate reference materials for interlaboratory comparisons to complement existing ones that are mostly isotopically unfractionated from the bulk silicate earth.
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BACKGROUND Many bioactive ingredients of medicinal plants are known to produce vaso-protective benefits. Puerarin is one of the major isoflavone glucosides found in the root of kudzu vine and it exerts an anti-inflammatory effect and many other pharmacological actions. However, the mechanism underlying the vascular effect of puerarin is incompletely understood. Therefore, the present study aims to examine how puerarin reduces endothelium-dependent contractions (EDCs) in mouse arteries. MATERIAL AND METHODS EDCs were evoked by acetylcholine (ACh) in isolated mouse carotid arteries with intact endothelium pretreated with Nω-NO2-L-Arg-OMe (L-NAME). The arteries were pretreated with puerarin and other pharmacological inhibitors before the addition of cumulative concentrations of ACh. The concentration of several prostaglandins (PGs) was measured by high performance liquid chromatography-coupled spectrometry (HPLC-MS). RESULTS EDCs induced by ACh only presented in endothelium-intact arteries pretreated by L-NAME and EDCs were prevented by the treatment with cyclooxygenase (COX) inhibitor indomethacin (3 µmol/L) or thromboxane prostanoid receptor (TP receptor) antagonist S18886 (30 nmol/L). Acute 40-minute treatment with puerarin reduced EDCs in a concentration-dependent manner without affecting U46619-induced contraction. However, treatment with puerarin did not inhibit ACh-induced production of prostaglandins (PGs) in endothelium-intact arteries. CONCLUSIONS The present results show that puerarin is able to suppress EDCs in mouse carotid arteries, independent of inhibition of TP receptor or COX2-derived PGs.
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Artérias Carótidas/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Isoflavonas/farmacologia , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/farmacologia , Acetilcolina/farmacologia , Animais , Ciclo-Oxigenase 1/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Camundongos , Miografia , NG-Nitroarginina Metil Éster/farmacologiaRESUMO
BACKGROUND AND AIM: Clot burden score (CBS) was designed to weight the thrombus status in cerebral anterior circulation. We performed a systematic review and meta-analysis to investigate the prognostic value of CBS in acute ischemic stroke (AIS) patients undergoing reperfusion therapies. METHODS: We searched relevant databases for eligible articles reporting CBS in AIS patients. The effect sizes of good functional outcome, recanalization, or hemorrhagic transformation (HT) were pooled with random-/fixed-effect models. Sensitivity analyses and heterogeneity tests were performed. RESULTS: Fifteen eligible studies enrolling 3302 AIS patients undergoing reperfusion therapies were included. AIS patients with per 1-point increase CBS were associated with good functional outcome (pooled odds ratio [OR]: 1.15, 95% confidence interval [CI]: 1.09-1.20) and high rate of recanalization (pooled OR: 1.27, 95% CI: 1.14-1.40). Results from categorical groups indicated high CBS at baseline was associated with higher likelihood of good functional outcome (pooled OR: 1.59, 95% CI: 1.30-1.94) and superior recanalization rates (pooled OR: 2.53, 95% CI: 1.79-3.57). Further stratified analyses showed in intravenous thrombolysis (IVT) alone group, increasing CBS was associated with good functional outcome (continuous pooled OR: 1.18, 95% CI: 1.10-1.27; categorical pooled OR: 3.38, 95% CI: 2.01-5.69) or recanalization (categorical pooled OR: 4.13, 95% CI: 2.00-8.51), but not in endovascular therapy alone group. No significant association was found between CBS and HT. CONCLUSIONS: CBS could be a predictor for AIS after reperfusion therapies in functional outcome and successful recanalization particularly in patients receiving IVT alone; while CBS might not be a predictor for HT.
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Isquemia Encefálica/terapia , Procedimentos Endovasculares , Trombose Intracraniana/terapia , Acidente Vascular Cerebral/terapia , Terapia Trombolítica , Idoso , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Terapia Trombolítica/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The common and major pathological change in ischemic stroke is atherosclerosis in the artery. Tumor necrosis factor-a (TNF-a) is closely related to the pathogenesis of atherosclerosis. The aim of our study was to investigate whether TNF-a gene variants (-238G/A and -308G/A) are associated with ischemic stroke. METHODS: A total of 619 ischemic stroke patients and 612 controls were recruited to estimate the frequencies of two TNF-a (-238G/A and -308G/A) single nucleotide polymorphisms using a Sequenom MassARRAY time-of-flight mass spectrometer. The association between TNF-a gene polymorphisms and ischemic stroke risk was evaluated by computing the odds ratio (OR) and 95% Confidence Interval with multivariate unconditional logistic regression analyses. RESULTS: The OR results indicated that no significant associations were found between TNF-a gene (-238G/A and -308G/A) polymorphisms and the risk of ischemic stroke using five genetic models, including the allele model (A vs. G), co-dominant model 1 (GA vs. GG), co-dominant model 2 (AA vs. GG), the dominant model (AA+GA vs. GG), and the recessive model (GG+GA vs. AA). CONCLUSIONS: The TNF-a (-238G/A and -308G/A) gene polymorphisms may not be a susceptible predictor of ischemic stroke in Chinese populations.
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Isquemia Encefálica/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Fatores de RiscoRESUMO
BACKGROUND: Many studies have investigated the association between the cyclooxygenase-2 (COX-2) gene polymorphism and ischemic stroke. However, results of these studies still remain controversial. To better explain the association between COX-2 polymorphisms (-765G/C and -1195G/A) and ischemic stroke risk, a meta-analysis was performed. METHODS: Relevant studies were identified from 4 Chinese databases (Chinese Biological Medical Literature database, Chinese National Knowledge Infrastructure database, Chongqing VIP database, and Chinese WANFANG database), PUBMED and EMBASE prior to December 2015. The strength of association between COX-2 polymorphism and ischemic stroke was evaluated by the odds ratio (OR) with 95% confidence interval (CI). Inconsistency index (I(2)) and the Cochran's Q statistic were used to check heterogeneity. Publication bias was evaluated by funnel plots and Egger's regression test. RESULTS: A total of 4086 ischemic stroke cases and 4747 controls were identified. Significant association between COX-2 -765G/C polymorphism and the risk of ischemic stroke was found in Brazilians and the African-Americans. The OR of (CC+GC versus GG) for the Brazilians and African-Americans were (6.328, 95% CI = 2.295-17.448) and (1.644, 95% CI = 1.060-2.551). In addition, the recessive model of the Brazilians gave an OR of 3.621 (95% CI: 1.519-8.630). Furthermore, the (GC versus GG) and the allele model of the African-Americans were (OR: 1.615, 95% CI = 1.015-2.572) and (OR: 1.422, 95% CI = 1.033-1.957). Significant association was also observed for COX-2 -1195G/A polymorphism in the subtypes of small vessel disease (SVD) of ischemic stroke. CONCLUSIONS: Our study suggests that COX-2 -765G/C and -1195G/A polymorphisms may contribute to susceptibility of ischemic stroke, specifically in Brazilians and the African-Americans, and those of SVD.
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Isquemia Encefálica/complicações , Isquemia Encefálica/genética , Ciclo-Oxigenase 2/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/genética , Negro ou Afro-Americano , Brasil , China , Estudos de Coortes , Estudos Transversais , Análise Mutacional de DNA , Bases de Dados Bibliográficas/estatística & dados numéricos , Feminino , Genótipo , Humanos , Masculino , Metanálise como AssuntoRESUMO
BACKGROUND: Several investigations have been performed to examine the influence of the ß-fibrinogen (FGß) gene polymorphisms on the risk of ischemic stroke, but the results of these studies are controversial. Our study aimed at investigating whether the FGß gene (-148 C/T, 448 G/A, and -854 G/A) polymorphisms were associated with susceptibility to ischemic stroke by conducting meta-analysis. METHODS: Relevant studies were identified from 4 Chinese databases, PUBMED and EMBASE before May 30, 2014. The strength of association was evaluated by the odds ratio with 95% confidence interval. Inconsistency index and the Cochran's Q statistic were used to check heterogeneity. Publication bias was tested using funnel plots and Egger's regression test. RESULTS: Thirty-two independent studies with 4311 cases and 4124 controls were included. Significant association between -148 C/T polymorphism and the risk of ischemic stroke was found in overall analysis and middle-age, but not in young adults and elderly people. Similarly, association was also observed for -854 G/A polymorphism, especially in cerebral arterial main trunk infarction (MCI) and cerebral penetrating arterial infarction (PCI). However, no significance was found between 448 G/A polymorphism and ischemic stroke in Chinese people; likewise, no evidence of a significant association was observed when stratified according to the subtype of ischemic stroke (MCI and PCI). CONCLUSIONS: These results suggest that -148 C/T and -854 G/A polymorphisms probably contribute to susceptibility of ischemic stroke.
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Povo Asiático/genética , Isquemia Encefálica/genética , Fibrinogênio/genética , Polimorfismo Genético , Acidente Vascular Cerebral/genética , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etnologia , Estudos de Casos e Controles , China/epidemiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etnologiaRESUMO
Many studies have investigated the association between the ß-fibrinogen gene-455G/A (FGß-455G/A) polymorphism and the risk of ischemic stroke. However, these evidences were inadequate to provide stronger conclusions because most studies were generally small. To shed light on these inconclusive findings, we conducted a large sample size meta-analysis of studies relating to the FGß-455G/A polymorphism and the risk of ischemic stroke. Odds ratios with a 95 % confidence interval were used to investigate the association between FGß-455G/A polymorphism and ischemic stroke. Publication bias was tested by Egger's test and funnel plot. Inconsistency index and Cochran's Q statistic were used to check heterogeneity. Cumulative and recursive cumulative meta-analyses were performed to provide a framework for updating a genetic effect from all of the included studies. Twenty-six independent publications with 4,070 cases and 4,649 controls were included in this meta-analysis. Results showed that the ß-fibrinogen-455G/A polymorphism was significantly associated with the risk of ischemic stroke. The FGß-455G/A polymorphism was found to be a risk factor for ischemic stroke in Asians and adults, while association was not observed for Caucasians and juveniles based on the small size and it may be necessary to conduct larger studies on them to investigate the association in the future. The cumulative meta-analysis indicated a decline from 1998 to 2003, and the results remained stable during the period 2004-2012. The results indicate that FGß-455G/A polymorphism may be a susceptible predictor of ischemic stroke. More studies are needed to elucidate the relationship further.
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Isquemia Encefálica/genética , Fibrinogênio/genética , Predisposição Genética para Doença , Polimorfismo Genético , Acidente Vascular Cerebral/genética , Fatores Etários , Alelos , Povo Asiático/genética , Isquemia Encefálica/epidemiologia , Humanos , Modelos Genéticos , Razão de Chances , Viés de Publicação , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , População Branca/genéticaRESUMO
BACKGROUND: The role of genetic variants in the pathogenesis of stroke has not been fully elucidated. Several studies have been examined the association of the Integrin alpha2 (ITGA2) gene-C807T (rs1126643) polymorphism with ischemic stroke susceptibility. However, the results of these studies are inconsistent. In order to explore this association more deeply, we performed a meta-analysis. METHODS: We collected case-control studies concerning the relationship between the C807T polymorphism and ischemic stroke, and odd ratios (OR) with corresponding 95% confidence intervals (CI) were used to describe the relationships. Inconsistency index (I(2)) and Cochran's Q statistic were used to check heterogeneity. Publication bias was tested by funnel plots and Egger's test. RESULTS: Fifteen studies with 2242 cases and 2408 controls were included. Our meta-analysis results indicated an association between the C807T polymorphism and the risk of ischemic stroke in the overall population, Asians and the subgroup of hospital-based people. However, statistically association was not observed for Caucasians and non-hospitalized individuals. CONCLUSIONS: The ITGA2 gene C807T polymorphism may be a susceptible predictor of the risk of ischemic stroke. More data are needed to elucidate the relationship further.
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Isquemia Encefálica/genética , Predisposição Genética para Doença/genética , Integrina alfa2/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Povo Asiático/genética , Isquemia Encefálica/complicações , Estudos de Casos e Controles , Estudos de Associação Genética , Hospitalização/estatística & dados numéricos , Humanos , Viés de Publicação/estatística & dados numéricos , Acidente Vascular Cerebral/complicações , População Branca/genéticaRESUMO
Background: Since the outbreak of COVID-19, China has implemented a series of non-pharmaceutical interventions (NPIs), effectively containing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as various respiratory pathogens. With the continuous relaxation of restrictions, China has entered a new phase of the post-pandemic era. However, the epidemiological differences of Mycoplasma pneumoniae (MP) between the two phases in Ningbo and even in China remain unclear. Methods: Data of children aged 0-14 years who visited the Ningbo Medical Center LiHuiLi Hospital due to acute respiratory tract infections from January 2020 to December 2023 were collected. PCR was used to detect 13 respiratory pathogens and the macrolide-resistance of Mycoplasma pneumoniae. Results: Among 10,206 children, 2,360 were infected with MP (23.12%). Among the total, the MP positive rate during the NPI phase (6.35%) was significantly lower than that during the non-NPI phase (34.28%), while the macrolide resistance rate increased from 62.5% (NPI phase) to 81.1% (non-NPI phase). The rate of MP co-infection increased from 11.2% (NPI phase) to 30.3% (non-NPI phase). MP infection exhibited obvious seasonality, with the highest prevalence in autumn (30.0%) followed by summer (23.6%). There were differences in MP positivity rates among different age groups, with the highest among school-age children at 39.5%. During the NPI phase, all age groups were less susceptible to MP, while during the non-NPI phase, the susceptible age for MP was 4-12 years, with 8 years being the most susceptible. The susceptible age for MP co-infection was 0-6 years. MP exhibited antagonistic effects against numerous pathogens. Compared to MP single infection, the proportion of pneumonia was higher in MP co-infection cases. Conclusion: The removal of NPIs significantly impacted the spread of MP, altering population characteristics including age, seasonality, macrolide resistance, and MP co-infection rates.
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In this experiment, a rapid and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was established and validated for the quantitation and pharmacokinetic analysis of eupafolin in rat plasma, utilizing licochalcone B as internal standard (IS). After liquid-liquid extraction of the analyte samples by ethyl acetate, chromatographic separation was achieved using a UPLC HSS T3 column under gradient elution conditions, with the mobile phase consisting of acetonitrile and water (with 0.1 % formic acid). Eupafolin was quantified by multiple reaction monitoring (MRM) in electrospray positive-ion mode (ESI+), employing the mass transition m/z 315.2 â 300.3 for eupafolin and m/z 285.4 â 270.3 for IS. Eupafolin demonstrated excellent linear relationship (r > 0.99) over the concentration range of 1.25-1250 ng/mL, with the lower limit of quantification (LLOQ) of the UPLC-MS/MS assay determined as 1.25 ng/mL. Method validation followed the bioanalytical method validation criteria outlined by the FDA. The accuracy of eupafolin ranged from 86.7 % to 111.2 %, and the precision was less than 12 %. The matrix effect was observed at 92.8 %-98.6 %, while the recoveries exceeded 83.2 %. The established UPLC-MS/MS assay was successfully employed for the pharmacokinetic evaluation of eupafolin in rats. The half-lives (t1/2z) were determined to be 1.4 ± 0.4 h and 2.5 ± 1.4 h for intravenous and oral administration, respectively. Notably, the bioavailability of eupafolin was relatively low (8.3 %). The optimized UPLC-MS/MS technology showed highly sensitive, selective, and effective, rendering it suitable for the pharmacokinetics of eupafolin in preclinical practice.
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Limite de Detecção , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Espectrometria de Massas em Tandem/métodos , Ratos , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes , Masculino , Modelos Lineares , Chalconas/farmacocinética , Chalconas/sangue , Chalconas/química , Sensibilidade e Especificidade , Espectrometria de Massa com Cromatografia LíquidaRESUMO
Salt stress is one of the most important factors limiting rice growth and yield increase. Salt tolerance of rice at the bud burst (STB) stage determines whether germinated seeds can grow normally under salt stress, which is very important for direct seeding. However, reports on quantitative trait loci (QTLs) and candidate genes for STB in rice are very limited. In this study, a natural population of 130 indica and 81 japonica rice accessions was used to identify STB-related QTLs and candidate genes using a genome-wide association study (GWAS). Nine QTLs, including five for relative shoot length (RSL), two for relative root length (RRL), and two for relative root number (RRN), were identified. Five of these STB-related QTLs are located at the same site as the characterized salt tolerance genes, such as OsMDH1, OsSRFP1, and OsCDPK7. However, an important QTL related to RSL, qRSL1-2, has not been previously identified and was detected on chromosome 1. The candidate region for qRSL1-2 was identified by linkage disequilibrium analysis, 18 genes were found to have altered expression levels under salt stress through the RNA-seq database, and 10 of them were found to be highly expressed in the shoot. It was also found that, eight candidate genes (LOC_Os01g62980, LOC_Os01g63190, LOC_Os01g63230, LOC_Os01g63280, LOC_Os01g63400, LOC_Os01g63460, and LOC_Os01g63580) for qRSL1-2 carry different haplotypes between indica and japonica rice, which exactly corresponds to the significant difference in RSL values between indica and japonica rice in this study. Most of the accessions with elite haplotypes were indica rice, which had higher RSL values. These genes with indica-japonica specific haplotypes were identified as candidate genes. Rice accessions with elite haplotypes could be used as important resources for direct seeding. This study also provides new insights into the genetic mechanism of STB.
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In Alzheimer's disease (AD), amyloid-beta (Aß) plays a crucial role in pathogenesis. Clearing Aß from the brain is considered as a key therapeutic strategy. Previous studies indicated that Salvia miltiorrhiza (Danshen) could protect against AD. However, the main anti-AD components in Danshen and their specific mechanisms are not clear. In this study, pharmacological network analysis indicated that Tanshinone IIA (Tan IIA) was identified as the key active compound in Danshen contributing to protect against AD. Then, APP/PS1 double transgenic mice were employed to examine the neuroprotective effect of Tan IIA. APP/PS1 mice (age, 6 months) were administered (10 and 20 mg/kg) for 8 weeks. Tan IIA improved learning and anxiety behaviors in APP/PS1 mice. Furthermore, Tan IIA reduced oxidative stress, inhibited neuronal apoptosis, improved cholinergic nervous system and decreased endoplasmic reticulum stress in the brain of APP/PS1 mice. Moreover, Tan IIA treatment reduced the level of Aß. Molecular docking result showed that Tan IIA might block AD by upregulating Aß-degrading enzymes. Western blot results confirmed that the expressions of insulin degrading enzymes (IDE) and neprilysin (NEP) were significantly increased after Tan IIA treatment, which demonstrated that Tan IIA improved AD by increasing Aß-degrading enzymes.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Salvia miltiorrhiza , Camundongos , Animais , Simulação de Acoplamento Molecular , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de DoençasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Taohong Siwu Decoction (TSD), a classic traditional Chinese medicine formula, is used for the treatment of vascular diseases, including vascular dementia (VD). However, the mechanisms remain unclear. AIM OF STUDY: This study aimed to investigate whether TSD has a positive effect on cognitive impairment in VD rats and to confirm that the mechanism of action is related to the Endoplasmic Reticulum stress (ERs) and cell apoptosis signaling pathway. MATERIALS AND METHODS: A total of 40 male adult Sprague-Dawley rats were divided into four groups: sham-operated group (Sham), the two-vessel occlusion group (2VO), the 2VO treated with 4.5 g/kg/d TSD group (2VO + TSD-L), the 2VO treated with 13.5 g/kg/d TSD group (2VO + TSD-H). The rats underwent either 2VO surgery or sham surgery. Postoperative TSD treatment was given for 4 consecutive weeks. Behavioral tests were initiated at the end of gastrulation. Open-field test (OFT) was used to detect the activity level. The New Object Recognition test (NOR) was used to test long-term memory. The Morris water maze (MWM) test was used to examine the foundation of spatial learning and memory. As a final step, the hippocampus was taken for molecular testing. The protein levels of GRP78 (Bip), p-PERK, PERK, IRE1α, p-IRE1α, ATF6, eIF2α, p-eIF2α, ATF4, XBP1, Bcl-2 and Bax were determined by Western blot. Immunofluorescence visualizes molecular expression. RESULTS: In the OFT, residence time in the central area was significantly longer in both TSD treatment groups compared to the 2VO group. In the NOR, the recognition index was obviously elevated in both TSD treatment groups. The 2VO group had a significantly longer escape latency and fewer times in crossing the location of the platform compared with the Sham group in MWM. TSD treatment reversed this notion. Pathologically, staining observations confirmed that TSD inhibited hippocampal neuronal loss and alleviated the abnormal reduction of the Nissl body. In parallel, TUNEL staining illustrated that TSD decelerated neuronal apoptosis. Western Blot demonstrated that TSD reduces the expression of ERs and apoptotic proteins. CONCLUSION: In this study, the significant ameliorative effect on cognitive impairment of TSD has been determined by comparing the behavioral data of the 4 groups of rats. Furthermore, it was confirmed that this effect of TSD was achieved by suppressing the ERs-mediated apoptosis signaling pathway.
Assuntos
Apoptose , Disfunção Cognitiva , Demência Vascular , Medicamentos de Ervas Chinesas , Estresse do Retículo Endoplasmático , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Medicamentos de Ervas Chinesas/farmacologia , Apoptose/efeitos dos fármacos , Demência Vascular/tratamento farmacológico , Demência Vascular/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Ratos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Modelos Animais de Doenças , Aprendizagem em Labirinto/efeitos dos fármacosRESUMO
Evodia lepta Merr. (Evodia lepta) is a well-known traditional Chinese medicine, which has been widely used in herbal tea. We previously reported that the coumarin compounds from the root of Evodia lepta exhibited neuroprotective effects. However, whether Evodia lepta could inhibit NLRP3 inflammasome in dementia was still unknown. In this study, the components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. We employed a scopolamine-treated mouse model. Evodia lepta extract (10 or 20 mg/kg) and donepezil were treated by gavage once a day for 14 consecutive days. Following the behavioral tests, oxidative stress levels were measured. Then, Western blot and immunofluorescence analysis were used to evaluate the expressions of NLRP3 inflammasome. 14 major components of the Evodia lepta extract were identified by HPLC-Q-TOF HRMS. The results of Morris water maze, object recognition task and open field test indicated that Evodia lepta extract could ameliorate cognitive impairment in scopolamine-treated mice. Evodia lepta extract improved cholinergic system. Moreover, Evodia lepta extract improved the expressions of PSD95 and BDNF. Evodia lepta extract suppressed neuronal oxidative stress and apoptosis. In addition, Evodia lepta extract inhibited NLRP3 inflammasome in the hippocampus of scopolamine-treated mice. Evodia lepta extract could protect against cognitive impairment by inhibiting NLRP3 inflammasome in scopolamine-treated mice.
Assuntos
Disfunção Cognitiva , Evodia , Camundongos , Animais , Inflamassomos , Evodia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Escopolamina/toxicidade , Etanol/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismoRESUMO
BACKGROUND: Stroke is the second highest cause of morbidity and functional disability around the world. In addition, it is the second most common cause of death worldwide [ 1 ]. However, the genetic pathology of stroke is still unclear. Published data on the association between TNF-a 238G/A polymorphisms and ischemic stroke risk are inconsistent and controversial. To provide a more robust estimate about TNF-a 238G/A polymorphisms on the risk of ischemic stroke, we conducted this meta-analysis. METHODS: We used the pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) to investigate the relationship between TNF-α238G/A polymorphisms and ischemic stroke. Publication bias was tested by Begg's test and inverted funnel plot, and Heterogeneity was checked by Cochran's Q statistic and the inconsistency index (I(2)). RESULTS: There are 7 studies that include 1,766 cases and 1,560 controls in this meta-analysis. The results indicated a significant association between TNF-α238G/A polymorphisms and ischemic stroke in overall analysis, Caucasian and Adult. However, statistical association was not observed in Juvenile and Asian. CONCLUSIONS: This meta-analysis suggests that TNF-α238G/A polymorphisms increases the risk of ischemic stroke in Adult, Caucasian, and overall analysis. However, in Juvenile and Asian analysis, significant associations between TNF-α238G/A and ischemic stroke were not found.
Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Fator de Necrose Tumoral alfa/genética , Isquemia Encefálica/complicações , Intervalos de Confiança , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Metanálise como Assunto , Razão de Chances , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Two single-nucleotide polymorphisms rs11833579 and rs12425791 located on chromosome 12p13 were reported to be associated with ischemic stroke in Caucasians. In the present study, we investigated whether the single-nucleotide polymorphism rs12425791 was associated with ischemic stroke in Chinese populations. METHODS: We carried out a case-control study examining a total of 166 Guangxi Han patients with ischemic stroke and 192 healthy controls. We also performed a meta-analysis of the data from our study and those from published studies to investigate whether an association between rs12425791 and ischemic stroke could be detected in Chinese populations. RESULTS: There was no statistically significant association between the single-nucleotide polymorphism rs12425791 and ischemic stroke in the Guangxi Han population. Our meta-analysis also found no significant association between rs12425791 and ischemic stroke in Chinese populations [allelic model odds ratio (OR) = 1.01, 95% confidence interval (CI), 0.96-1.07; dominant model OR = 1.01, 95%CI, 0.94-1.10; recessive model OR = 1.00, 95%CI, 0.86-1.17]. CONCLUSIONS: The single-nucleotide polymorphism rs12425791 does not confer a substantial risk for ischemic stroke in Chinese populations.
Assuntos
Povo Asiático/genética , Isquemia Encefálica/genética , Cromossomos Humanos Par 12/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/genética , Isquemia Encefálica/complicações , Estudos de Casos e Controles , Humanos , Acidente Vascular Cerebral/complicaçõesRESUMO
OBJECTIVE: To explore the correlation between 12p13 single nucleotide polymorphism (SNP) rs12425791 and Chinese medical syndrome types of ischemic stroke patients of the Han nationality. METHODS: A case-control study was used. Recruited were 148 ischemic stroke patients of the Han nationality (67 patients of phlegm syndrome and 81 patients of blood stasis syndrome). Another 192 healthy subjects were recruited as the control group. The genotypes of rs12425791 were performed by TaqMan SNP genotyping assays to analyze the distribution of genes and the distribution frequency of alleles. RESULTS: There was no statistical difference in the genotype and alleles of rs12425791 between the ischemic stroke patients of phlegm syndrome and the control group, or between the ischemic stroke patients of blood stasis syndrome and the control group (P > 0.05). CONCLUSION: Our results did not support that 12p13 common variant rs12425791 was correlated with the pathogeneses of ischemic stroke patients of phlegm syndrome and ischemic stroke patients of blood stasis syndrome.