RESUMO
BACKGROUND: Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. METHODS: A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan-Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. RESULTS: During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan-Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05-1.71), 1.52 (1.19-1.93), and 1.84 (1.45-2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. CONCLUSIONS: An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual's glucose metabolism status.
Assuntos
Biomarcadores , Glicemia , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Glicemia/metabolismo , Biomarcadores/sangue , China/epidemiologia , Medição de Risco , Incidência , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Estudos Longitudinais , Prognóstico , Resistência à Insulina , Triglicerídeos/sangue , HDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/diagnóstico , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/diagnóstico , Estudos ProspectivosRESUMO
Synaptic dysfunction plays a crucial role in the pathogenesis of Alzheimer's disease (AD). α/ß-hydrolase domain-containing 6 (ABHD6) contributes to synaptic dysfunctions, and ABHD6 inhibition has shown potential therapeutic value in neurological disorders. However, the role of ABHD6 in AD has not been fully defined. In this study, we demonstrated that adeno-associated virus (AAV) mediated shRNA targeting ABHD6 in hippocampal neurons attenuated synaptic dysfunction and memory impairment of APPswe/PS1dE9 (APP/PS1) mice, while it didn't affect the amyloid-beta (Aß) levels and neuroinflammation in the brains. In addition, intraperitoneal injection of wwl70, a specific inhibitor of ABHD6, improved synaptic plasticity and memory function in APP/PS1 mice, which might attribute to the activation of endogenous cannabinoid signaling. Furthermore, wwl70 significantly decreased the Aß levels and neuroinflammation in the hippocampus of AD mice, and enhanced Aß phagocytized by microglia. In conclusion, for the first time our data have shown that ABHD6 inhibition might be a promising strategy for AD treatment, and wwl70 is a potential candidate for AD drug development pipeline.
Assuntos
Doença de Alzheimer , Hidrolases , Animais , Camundongos , Doença de Alzheimer/genética , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide , Modelos Animais de Doenças , Transtornos da Memória/tratamento farmacológico , Camundongos Transgênicos , Monoacilglicerol Lipases , Doenças NeuroinflamatóriasRESUMO
BACKGROUND: The true incidence of acute gastrointestinal illness in China is underrecognized by surveillance systems. The aims of this study were to estimate the incidence and prevalence of self-reported AGI in the community of China, and to investigate sociodemographic and epidemiological determinants of AGI. METHODS: We conducted a 12-months cross-sectional population-based survey in eight provinces of China during 2014-2015. The survey determined the prevalence and incidence of acute gastrointestinal illness (AGI) in the total permanent resident population in China according to the census of the population in 2010. The random multilevel population sample was stratified by geographic, population, and socioeconomic status. We used a recommended case definition of AGI, with diarrhea (three loose or watery stools) and/or any vomiting in a four-week recall. A face-to-face survey was conducted by selecting the member in the household with the most recent birthday. RESULTS: Among 56,704 sampled individuals, 948 (1,134 person-time) fulfilled the case definition; 98.5% reported diarrhea. This corresponds to 2.3% (95% CI:1.9%-2.8%) of an overall standardized four-week prevalence and 0.3 (95% CI: 0.23-0.34) episodes per person-year of annual adjusted incidence rate. There was no significant difference between males and females. The incidence rates were higher among urban residents, and in the spring and summer. In the whole study period, 50% of the cases sought medical care, of which 3.9% were hospitalized and 14.3% provided a biological sample for laboratory identification of the causative agent. Children aged 0-4 and young adults aged 15-24, people living in rural areas and people who traveled frequently had higher prevalence of AGI. CONCLUSION: Results showed that AGI represents a substantial burden in China, and will contribute to the estimation of the global burden of AGI. Complemented with data on the etiologies of AGI, these estimates will form the basis to estimate the burden of foodborne diseases in China.
Assuntos
Diarreia , Vômito , Criança , Feminino , Masculino , Adulto Jovem , Humanos , Estudos Transversais , Prevalência , Diarreia/epidemiologia , China/epidemiologiaRESUMO
Voltage-gated KV1.3 channel has been reported to be a drug target for the treatment of autoimmune diseases, and specific inhibitors of Kv1.3 are potential therapeutic drugs for multiple diseases. The scorpions could produce various bioactive peptides that could inhibit KV1.3 channel. Here, we identified a new scorpion toxin polypeptide gene ImKTX58 from the venom gland cDNA library of the Chinese scorpion Isometrus maculatus Sequence alignment revealed high similarities between ImKTX58 mature peptide and previously reported KV1.3 channel blockers-LmKTX10 and ImKTX88-suggesting that ImKTX58 peptide might also be a KV1.3 channel blocker. By using electrophysiological recordings, we showed that recombinant ImKTX58 prepared by genetic engineering technologies had a highly selective inhibiting effect on KV1.3 channel. Further alanine scanning mutagenesis and computer simulation identified four amino acid residues in ImKTX58 peptide as key binding sites to KV1.3 channel by forming hydrogen bonds, salt bonds, and hydrophobic interactions. Among these four residues, 28th lysine of the ImKTX58 mature peptide was found to be the most critical amino acid residue for blocking KV1.3 channel. SIGNIFICANCE STATEMENT: In this study, we discovered a scorpion toxin gene ImKTX58 that has not been reported before in Hainan Isometrus maculatus and successfully used the prokaryotic expression system to express and purify the polypeptides encoded by this gene. Electrophysiological experiments on ImKTX58 showed that ImKTX58 has a highly selective blocking effect on KV1.3 channel over Kv1.1, Kv1.2, Kv1.5, SK2, SK3, and BK channels. These findings provide a theoretical basis for designing highly effective KV1.3 blockers to treat autoimmune and other diseases.
Assuntos
Venenos de Escorpião , Sequência de Aminoácidos , Aminoácidos , Animais , Simulação por Computador , Canal de Potássio Kv1.3/química , Canal de Potássio Kv1.3/genética , Canal de Potássio Kv1.3/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Peptídeos/química , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/farmacologia , Venenos de Escorpião/química , Venenos de Escorpião/metabolismo , Venenos de Escorpião/farmacologia , Escorpiões/química , Escorpiões/genética , Escorpiões/metabolismoRESUMO
Previous studies have shown that ovarian estrogens are involved in the occurrence and pathology of Alzheimer's disease (AD) through regulation on hippocampal synaptic plasticity and spatial memory; however, the underlying mechanisms have not yet been elucidated at the genomic scale. In this study, we established the postmenopausal estrogen-deficient model by ovariectomy (OVX). Then, we used high-throughput Affymetrix Clariom transcriptomics and found 143 differentially expressed genes in the hippocampus of OVX mice with the absolute fold change ≥ 1.5 and P < 0.05. GO analysis showed that the highest enrichment was seen in long-term memory. Combined with the response to steroid hormone enrichment and GeneMANIA network prediction, the serum and glucocorticoid-regulated kinase 1 gene (Sgk1) was found to be the most potent candidate for ovarian estrogenic regulation. Sgk1 overexpression viral vectors (oSgk1) were then constructed and injected into the hippocampus of OVX mice. Morris water maze test revealed that the impaired spatial learning and memory induced by OVX was rescued by Sgk1 overexpression. Additionally, the altered expression of synaptic proteins and actin remodeling proteins and changes in CA1 spine density and synapse density induced by OVX were also significantly reversed by oSgk1. Moreover, the OVX-induced increase in Aß-producing BACE1 and Aß and the decrease in insulin degrading enzyme were significantly reversed by oSgk1. The above results show that multiple pathways and genes are involved in ovarian estrogenic regulation of the function of the hippocampus, among which Sgk1 may be a novel potent target against estrogen-sensitive hippocampal dysfunctions, such as Aß-initiated AD.
Assuntos
Doença de Alzheimer , Proteínas Imediatamente Precoces , Insulisina , Proteínas Serina-Treonina Quinases , Actinas/metabolismo , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Estrogênios/metabolismo , Feminino , Hipocampo/metabolismo , Proteínas Imediatamente Precoces/genética , Insulisina/metabolismo , Aprendizagem em Labirinto , Camundongos , Proteínas Serina-Treonina Quinases/genética , Aprendizagem Espacial , Memória Espacial/fisiologia , TranscriptomaRESUMO
Ovarian estrogens (mainly 17ß estradiol, E2) have been involved in the regulation of the structure of hippocampus, the center of spatial memory. In recent years, high levels of aromatase (AROM), the estrogen synthase, has been localized in hippocampus; and this hippocampus-derived E2 seems to be functional in synaptic plasticity and spatial memory as ovarian E2 does. However, the contribution of ovarian E2 and hippocampal E2 to spatial memory and neural plasticity remains unclear. In this study, AROM-specific RNA interference AAVs (shAROM) were constructed and injected into the hippocampus of control or ovariectomized (OVX) mice. Four weeks later the spatial learning and memory behavior was examined with Morris water maze, the expression of hippocampal Aß related proteins, selected synaptic proteins and CA1 synapse density, actin polymerization related proteins and CA1 spine density were also examined. The results showed that while OVX and hippocampal shAROM contributed similarly to most of the parameters examined, shAROM induced more increase in BACE1 (amyloidogenic ß-secretase), more decrease in neprilysin (Aß remover) and Profilin-1 (actin polymerization inducer). More importantly, combined OVX and shAROM treatment displayed most significant impairment of spatial learning and memory as well as decrease in synaptic plasticity compared to OVX or shAROM alone. In conclusion, the above results clearly demonstrated the crucial role of hippocampal E2 in the regulation of the structure and function of hippocampus besides ovarian E2, indicating that hippocampal E2 content should also be taken into consideration during estrogenic replacement.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Aromatase/metabolismo , Plasticidade Neuronal/fisiologia , Memória Espacial/fisiologia , Animais , Aromatase/genética , Sequência de Bases , Região CA1 Hipocampal/enzimologia , Região CA1 Hipocampal/metabolismo , Espinhas Dendríticas/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Camundongos Endogâmicos C57BL , Teste do Labirinto Aquático de Morris/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Ovariectomia/efeitos adversos , Ovário/enzimologia , RNA Interferente Pequeno/farmacologia , Aprendizagem Espacial/fisiologia , Sinapses/metabolismoRESUMO
BACKGROUND: Meier-Gorlin syndrome 7 (MGS7) is a rare autosomal recessive condition. We reported a fetus diagnosed with Meier-Gorlin syndrome 7. The antenatal sonographic images were presented, and compound heterozygous mutations of CDC45 on chromosome 22 were identified by whole-exome sequencing (WES). CASE PRESENTATION: Fetal growth restriction (FGR), craniosynostosis, and brachydactyly of right thumb were found in a fetus of 28th gestational weeks. The fetus was diagnosed as MGS7 clinically. After extensive counseling, the couple opted for prenatal diagnosis by cordocentesis and termination of pregnancy. Karyotype analysis and WES were performed. Chromosomal karyotyping showed that the fetus was 46, XY. There were 2 mutations of CDC45, the causal gene of MGS7 on chromosome 22, which were inherited from the couple respectively were identified by WES. Facial dysmorphism, brachydactyly of right thumb, and genitalia abnormally were proved by postpartum autopsy, and craniosynostosis was confirmed by three-dimensional computed tomography (3D-CT) reconstruction. CONCLUSIONS: It is possible to detect multiple clinical features of Meier-Gorlin syndrome in prenatal sonography. Deteriorative FGR complicated with craniosynostosis indicates MGS7. Combination of 2D and 3D ultrasonography helps to detect craniosynostosis. The affected fetus was confirmed a compound heterozygote of CDC45 related MGS by whole-exome sequencing, which is critical in identifying rare genetic diseases.
Assuntos
Microtia Congênita/diagnóstico por imagem , Transtornos do Crescimento/diagnóstico por imagem , Micrognatismo/diagnóstico por imagem , Patela/anormalidades , Ultrassonografia Pré-Natal , Aborto Induzido , Povo Asiático , China/etnologia , Feminino , Humanos , Masculino , Patela/diagnóstico por imagem , Gravidez , Segundo Trimestre da Gravidez , Adulto JovemRESUMO
The volatile oil of Curcumae Rhizoma has many active components,which are the key to the quality of Curcumae Rhizoma. Exploring the difference between volatile oil of different kinds of Curcumae Rhizoma facilitates the quality control and rational application of resources. In this study,GC-MS was applied to realize online qualitative and semi-quantitative analysis of the chemical composition spectrum of volatile oil from Curcuma wenyujin( CW),C. phaeocaulis( CP),and C. kwangsiensis( CK). Forty components were identified and their fingerprints were compared and evaluated. Hierarchical cluster analysis( HCA),principal component analysis( PCA),and orthogonal partial least squares discrimination analysis( OPLS-DA) were adopted to analyze the overall and outlier data. The results showed that the whole data could be divided into three kinds according to each analysis mode,and the volatile components of Curcumae Rhizoma vary greatly among species. PCA explored the difference between outliers and the mean value of the group and found that some volatile oils from CW may be greatly affected by the origin. By OPLS-DA,the samples from Zhejiang were able to gather,but those from Guizhou remained isolated,indicating the influence of growing environment on Curcumae Rhizoma metabolites. Based on VIP results combined with the heat map,characteristic volatile oil components of Curcumae Rhizoma from different varieties were screened out: curdione and linalool for CW; 2-undecanone for CP; humulene,γ-selinene,and zederone for CK. The GCMS method established in this study describes Curcumae Rhizoma samples comprehensively and accurately,and the characteristic components screened based on chemometrics can be used to distinguish Curcumae Rhizoma from different varieties and give them unique pharmacodynamic significance,which is fast,convenient,stable,and reliable and supports the rational application of Curcu-mae Rhizoma resources. It is found that the region of origin has great influence on CW,which is worthy of further study.
Assuntos
Óleos Voláteis , Curcuma , Cromatografia Gasosa-Espectrometria de Massas , Análise de Componente Principal , RizomaRESUMO
Both cadmium (Cd) and lead (Pb) are associated with bone health, but studies exploring the effects of Cd and Pb co-exposure on bone health are rare. This study aimed to assess the interactive effects of Cd and Pb co-exposure on bone health. In total, 799 participants, living in the targeted areas (located in southwestern China) for more than 15 years, aged 40-75 years, and subsisted on homegrown rice and vegetables were investigated. Cd and Pb levels in urine and blood samples, as well as bone mineral density, T- and Z-score were determined. After being adjusted for covariates, the T-score was negatively correlated with blood Pb in men (P < .05); for women and non-smoking women, the T-score was negatively correlated with urinary Pb (P < .05). Moreover, after being adjusted for covariates, the Z-score was negatively correlated with urinary Pb in non-smoking women (P < .05). No positive association of prevalence of osteoporosis with Cd and Pb exposure was found. However, at an additive scale, positive interactions of urinary Cd and Pb on the prevalence of osteoporosis for women and non-smoking women, and the same interactions to blood Cd and Pb for men were found. There was also a positive interaction of urinary Cd and Pb for women at a multiplicative scale. This study suggests Cd and Pb exposure could exert detrimental effects on bone health, with possible underlying interactions. Nevertheless, more studies are needed to explore the interactive effects of heavy metal co-exposure.
Assuntos
Densidade Óssea , Cádmio , Chumbo , Osteoporose/epidemiologia , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Cádmio/sangue , Cádmio/urina , China , Feminino , Humanos , Chumbo/sangue , Chumbo/urina , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/urina , Prevalência , Medição de Risco , Fatores de Risco , Fatores SexuaisRESUMO
Metal exposure has recently been related to the risk of hypertension. However, the association remains unclear and relevant epidemiologic studies are limited. The present study aimed to assess the associations between exposure to metals and the odds of hypertension, as well as blood pressure (BP) levels. A total of 816 participants were enrolled in southwestern China. Hypertension was defined as a systolic BP (SBP) of ≥140 mmHg or diastolic BP (DBP) of ≥90 mmHg, a self-reported physician diagnosis, or current use of antihypertensive medication. Blood samples were used to detect the levels of exposure to metals, ie, magnesium (Mg), calcium (Ca), iron (Fe), zinc (Zn), arsenic (As), cadmium (Cd), copper (Cu) and lead (Pb). Logistic and linear regression models were used to assess the potential associations. The results show that positive trends for elevated odds of hypertension with increasing quartiles of Fe in a polluted area; and of Mg, Ca and Cu in an unpolluted area. Compared with those in the lowest quartiles, participants in the highest quartiles of Fe, Mg and Ca had 2.7-, 9.0- and 5.1-fold increased odds of hypertension, respectively. High blood Fe and Pb levels in the Cd-polluted area, and Mg and Fe in the unpolluted area were found to be related to increasing SBP and DBP levels. Our findings suggest that exposure to Fe and/or Pb in the polluted area; and Mg, Ca and Fe in the unpolluted area might increase the risk of hypertension or elevate BP levels.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , Hipertensão/induzido quimicamente , Metais Pesados/sangue , Metais Pesados/toxicidade , Adulto , Idoso , Arsênio/sangue , Arsênio/toxicidade , Cádmio/sangue , Cádmio/toxicidade , Cálcio/sangue , Cálcio/toxicidade , China , Cobre/sangue , Cobre/toxicidade , Feminino , Humanos , Ferro/sangue , Ferro/toxicidade , Magnésio/sangue , Magnésio/toxicidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Zinco/sangue , Zinco/toxicidadeRESUMO
This study aimed to establish a rapid and accurate method for identification of raw and vinegar-processed rhizomes of Curcuma kwangsiensis, in order to predict the content of curcumin compounds for scientific evaluation. A complete set of bionics recognition mode was adopted. The digital odor signal of raw and vinegar-processed rhizomes of Curcuma kwangsiensis were obtained by e-nose, and analyzed by back propagation(BP) neural network algorithm, with the accuracy, the sensitivity and specificity in discriminant model, correlation coefficient as well as the mean square error in regression model as the evaluation indexes. The experimental results showed that the three indexes of the e-nose signal discrimination model established by the neural network algorithm were 100% in training set, correction set and prediction set, which were obviously better than the traditional decision tree, naive bayes, support vector machine, K nearest neighbor and boost classification, and could accurately differentiate the raw and vinegar products. Correlation coefficient and mean square error of the regression model in prediction set were 0.974 8 and 0.117 5 respectively, and could well predict curcumin compounds content in Curcuma kwangsiensis, and demonstrate the superiority of the simulation biometrics model in the analysis of traditional Chinese medicine. By BP neural network algorithm, e-nose odor fingerprint could quickly, conveniently and accurately realize the discrimination and regression, which suggested that more bionics information acquisition and identification patterns could be combined in the field of traditional Chinese medicine, so as to provide ideas and methods for the rapid evaluation and stan-dardization of the quality of traditional Chinese medicine.
Assuntos
Curcumina , Nariz Eletrônico , Ácido Acético , Teorema de Bayes , Curcuma , Redes Neurais de Computação , RizomaRESUMO
BACKGROUND: The phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway is commonly deregulated in human cancer, hence many PI3K and mTOR inhibitors have been developed and have now reached clinical trials. Similarly, CDKs have been investigated as cancer drug targets. METHODS: We have synthesised and characterised a series of 6-aminopyrimidines identified from a kinase screen that inhibit PI3K and/or mTOR and/or CDK2. Kinase inhibition, tumour cell growth, cell cycle distribution, cytotoxicity and signalling experiments were undertaken in HCT116 and HT29 colorectal cancer cell lines, and in vivo HT29 efficacy studies. RESULTS: 2,6-Diaminopyrimidines with an O(4)-cyclohexylmethyl substituent and a C-5-nitroso or cyano group (1,2,5) induced cell cycle phase alterations and were growth inhibitory (GI50<20 µM). Compound 1, but not 2 or 5, potently inhibits CDK2 (IC50=0.1 nM) as well as PI3K, and was cytotoxic at growth inhibitory concentrations. Consistent with kinase inhibition data, compound 1 reduced phospho-Rb and phospho-rS6 at GI50 concentrations. Combination of NU6102 (CDK2 inhibitor) and pictilisib (GDC-0941; pan-PI3K inhibitor) resulted in synergistic growth inhibition, and enhanced cytotoxicity in HT29 cells in vitro and HT29 tumour growth inhibition in vivo. CONCLUSIONS: These studies identified a novel series of mixed CDK2/PI3K inhibitors and demonstrate that dual targeting of CDK2 and PI3K can result in enhanced antitumour activity.
Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adenocarcinoma/enzimologia , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Colorretais/enzimologia , Quinase 2 Dependente de Ciclina/fisiologia , Humanos , Camundongos , Camundongos Nus , Proteínas de Neoplasias/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Large numbers of the small brown planthopper Laodelphax striatellus (Fallén) (Hemiptera: Delphacidae) occur in temperate regions, causing severe losses in rice, wheat, and other economically important crops. The planthoppers enter diapause in the third- or fourth-instar nymph stage, induced by short photoperiods and low temperatures. To investigate the geographic variation in L. striatellus diapause, we compared the incidence of nymphal diapause under various constant temperature (20 and 27 °C) and a photoperiod of 4:20, 8:16, 10:14, 12:12, 14:10, and 16:8 (L:D) h regimes among three populations collected from Hanoi (21.02° N, 105.85° E, northern Vietnam), Jiangyan (32.51° N, 120.15° E, eastern China), and Changchun (43.89° N, 125.32° E, north-eastern China). Our results indicated that there were significant geographic variations in the diapause of L. striatellus. When the original latitude of the populations increased, higher diapause incidence and longer critical photoperiod (CP) were exhibited. The CPs of the Jiangyan and Changchun populations were â¼ 12 hr 30 min and 13 hr at 20 °C, and 11 hr and 11 hr 20 min at 27 °C, respectively. The second- and third-instar nymphs were at the stage most sensitive to the photoperiod. However, when the fourth- and fifth-instar nymphs were transferred to a long photoperiod, the diapause-inducing effect of the short photoperiod on young instars was almost reversed. The considerable geographic variations in the nymphal diapause of L. striatellus reflect their adaptation in response to a variable environment and provide insights to develop effective pest management strategies.
Assuntos
Diapausa de Inseto/fisiologia , Hemípteros/fisiologia , Fotoperíodo , Animais , China , Feminino , Masculino , Ninfa/fisiologia , Temperatura , VietnãRESUMO
The aim of the present study was to establish a new method based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) to determine the quality of different samples of Poria cocos (Schw.) Wolf obtained from Yunnan, Hubei, Guizhou, Fujian, Henan, Guangxi, Anhui and Sichuan in China. For this purpose 15 samples from the different habitats were analyzed by HPLC-PAD and HPLC-MS(n). Twenty-three compounds were detected by HPLC-MS(n), of which twenty compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. The characteristic fragmentations were summarized. 3-epi-Dehydrotumulosic acid (F13), 3-oxo-16α,25-dihydroxylanosta-7,9(11),24(31)-trien-21-oic acid (F4), 3-oxo-6,16α-dihydroxylanosta-7,9(11),24(31)-trien-21-oic acid (F7) and dehydropachymic acid (F15) were deemed to be suitable marker compounds to distinguish between samples of different quality according to CA and PCA. This study provides helpful chemical information for further anti-tumor activity and active mechanism research on P. cocos. The results proved that fingerprint combined with a chemometric approach is a simple, rapid and effective method for the quality discrimination of P. cocos.
Assuntos
Produtos Biológicos/análise , Poria/química , Triterpenos/isolamento & purificação , Produtos Biológicos/química , Cromatografia Líquida de Alta Pressão/métodos , Análise por Conglomerados , Espectrometria de Massas/métodos , Análise de Componente Principal , Triterpenos/químicaRESUMO
Botanical origins of propolis are significant factors affecting biological and pharmacological activities because of different components in propolis. Until now, the determination of propolis botanical origins is mainly based on different varieties and the content of the compositions with great limitations. Therefore, it is important to discriminate different botanical origins of propolis quickly and accurately. In this study, Near-infrared (NIR) spectra of propolis varieties based on principal component analysis mahalanobis distance (PCA-mahalanobis distance) model and canonical discriminant analysis model were built for the classification of three botanical origins (poplar propolisï¼brich propolis and rubber propolis). The models were built based on the optimal pretreatment method and bands of first derivative + Savitzky-Golay (7) filter and 4500~12 000-1, which were selected in advance. After the principal component analysis, the correct classification rates of calibration sets and validation sets in analysis mahalanobis distance models were 93.62% and 82.61%, respectively. The discrimination rate and the cross-validation rate of canonical discrimination models were 91.4% and 88.6%, respectively. Therefore, NIR spectroscopy with chemometric methods is not only feasible but also practical for rapid and accurate identification of varieties of propolis.
RESUMO
By adopting inductively coupled plasma mass spectrometry (ICP-MS) combined with chemometric analysis technology, 23 kinds of minerals in four kinds of characteristic honey derived from Yunnan province were analyzed. The result showed that 21 kinds of mineral elements, namely Na, Mg, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Sb, Ba, Tl and Pb, have significant differences among different varieties of honey. The results of principal component analysis (PCA) showed that the cumulative variance contribution rate of the first four main components reached 77.74%, seven kinds of elements (Mg, Ca, Mn, Co, Sr, Cd, Ba) from the first main component contained most of the honey information. Through the stepwise discriminant analysis, seven kinds of elements (Mg, K, Ca, Cr, Mn, Sr, Pb) were filtered. out and used to establish the discriminant function model, and the correct classification rates of the proposed model reached 90% and 86.7%, respectively, which showed elements contents could be effectively indicators to discriminate the four kinds characteristic honey in southern Yunnan Province. In view of all the honey samples were harvested from apiaries located at south Yunnan Province where have similar climate, soil and other environment conditions, the differences of the mineral elements contents for the honey samples mainly due to their corresponding nectariferous plant. Therefore, it is feasible to identify honey botanical source through the differences of mineral elements.
Assuntos
Mel/análise , Espectrometria de Massas , China , Análise Discriminante , Minerais/análise , Análise de Componente Principal , Análise EspectralRESUMO
Salvia miltiorrhiza is one of the most common traditional Chinese medicines. It has rich resources in China. According to modern studies, phenolic acids are the main effective components in S. miltiorrhiza. These components have cardiovascular and cerebrovascular protective effect, and anti-tumor, antioxidant, anti-inflammatory, and antifibrotic activities, etc. It has been widely used for the treatment of cardiovascular and cerebrovascular diseases and others. In this paper, the chemicals and pharmacological effects of phenolic acids from S. miltiorrhiza were summarized in the last decade. Its researches and development prospects were also analyzed for further studying and comprehensive utilization of these phenolic acids.
Assuntos
Alcenos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Polifenóis/farmacologia , Salvia miltiorrhiza/química , Alcenos/química , Animais , Tratamento Farmacológico , Medicamentos de Ervas Chinesas/química , Humanos , Estrutura Molecular , Polifenóis/químicaRESUMO
AIM: Fructus phyllanthi tannin fraction (PTF) from the traditional Tibetan medicine Fructus phyllanthi has been found to inhibit lung and liver carcinoma in mice. In this study we investigated the anticancer mechanisms of PTF in human lung squamous carcinoma cells in vitro. METHODS: Human lung squamous carcinoma cell line (NCI-H1703), human large-cell lung cancer cell line (NCI-H460), human lung adenocarcinoma cell line (A549) and human fibrosarcoma cell line (HT1080) were tested. Cell viability was detected with MTT assay. Cell migration and invasion were assessed using a wound healing assay and a transwell chemotaxis chambers assay, respectively. Cell apoptosis was analyzed with flow cytometric analysis. The levels of apoptosis-related and metastasis-related proteins were detected by Western blot and immunofluorescence. RESULTS: PTF dose-dependently inhibited the viability of the 3 human lung cancer cells. The IC50 values of PTF in inhibition of NCI-H1703, NCI-H460, and A549 cells were 33, 203, and 94 mg/L, respectively. PTF (15, 30, and 60 mg/L) dose-dependently induced apoptosis of NCI-H1703 cells. Treatment of NCI-H1703 and HT1080 cells with PTF significantly inhibited cell migration, and reduced the number of invasive cells through Matrigel. Furthermore, PTF dose-dependently down-regulated the expression of phosphor-ERK1/2, MMP-2 and MMP-9, up-regulated the expression of phosphor-JNK, but had no significant effect on the expression of ERK1/2 or JNK. CONCLUSION: PTF induces cell apoptosis and inhibits the migration and invasion of NCI-H1703 cells by decreasing MPPs expression through regulation of the MAPK pathway.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinases da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Taninos/farmacologia , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Concentração Inibidora 50 , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Medicina Tradicional Tibetana , Invasividade Neoplásica , Fosforilação , Fatores de TempoRESUMO
In order to identify honeys according to their floral origin, inductively coupled plasma mass spectrometry (ICP-MS) combined with principal component analysis (PCA) and discriminant analysis (DA) were employed in the present study. Three kinds of honeys such as acacia honey samples, sunflower honey samples and rape honey samples were selected. It was pretreated by wet-acid digestionand measured 20 kinds of mineral elements in honey samples by ICP-MS. The result showed that the accuracy of the inductively coupled plasma mass spectrometrymeted the requirements. The result of principal component analysis demonstrated that the acacia honey samples were performed a trend of certain gather. The trend of the sunflower honey samples and the rape honey samples are not obvious. Ten kinds of mineral elements including Na, Mg, K, Ca, Sr, Ba, V, Fe, Ni, Sb can be regarded as honey varieties of characteristic elements. Seven kinds of mineral elements such as Mg, Sr, Ba, Sb, Ni, Cr and Na could be selected through stepwise discriminant analysis. Using bayes discriminant analysis, A linear discriminant function can be recieved. The discrimination rate of honey samples such as acacia honey samples, sunflower samples and rape honey samples were 100%, 80% and 90. 9% respectively. Two sunflower honey samples was misclassified into rape honey samples an-done rape honey samples are also misclassified into acacia honey sample. The total rate of discriminant model cross validation was 90. 3%. It is concluded that the mineral elements in honey varieties with good classification. The present study can provide theoretical basis and the relationship between thetypes of honey samples with mineral elements. The method what this study used had simple, accurate and stablecharacteristics, which can be used as a reliable method of honey sample identification.
Assuntos
Mel/análise , Espectrometria de Massas , Análise Discriminante , Mel/classificação , Análise de Componente PrincipalRESUMO
At present, the rice syrup as a low price of the sweeteners was often adulterated into acacia honey and the adulterated honeys were sold in honey markets, while there is no suitable and fast method to identify honey adulterated with rice syrup. In this study, Near infrared spectroscopy (NIR) combined with chemometric methods were used to discriminate authenticity of honey. 20 unprocessed acacia honey samples from the different honey producing areas, mixed? with different proportion of rice syrup, were prepared of seven different concentration gradient? including 121 samples. The near infrared spectrum (NIR) instrument and spectrum processing software have been applied in the? spectrum? scanning and data conversion on adulterant samples, respectively. Then it was analyzed by Principal component analysis (PCA) and canonical discriminant analysis methods in order to discriminating adulterated honey. The results showed that after principal components analysis, the first two principal components accounted for 97.23% of total variation, but the regionalism of the score plot of the first two PCs was not obvious, so the canonical discriminant analysis was used to make the further discrimination, all samples had been discriminated correctly, the first two discriminant functions accounted for 91.6% among the six canonical discriminant functions, Then the different concentration of adulterant samples can be discriminated correctly, it illustrate that canonical discriminant analysis method combined with NIR spectroscopy is not only feasible but also practical for rapid and effective discriminate of the rice syrup adulterant of acacia honey.