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Lidar is an effective remote sensing method to obtain the vertical distribution of aerosols, and how to select the aerosol extinction-backscattering ratio (AE-BR) during the inversion process is a key step to guarantee the accuracy of the lidar inversion of aerosol optical thickness (AOD) and aerosol extinction coefficient profile (AECP). In this paper, an inversion algorithm for AOD and AECP based on a genetic BP (GA-BP) neural network is proposed. Simultaneous measurements are carried out using CE318 sun photometer and lidar, and the mapping relationship between the lidar echo signal and AOD is established based on the genetic BP (GA-BP) neural network method, which achieves the accurate inversion of AOD with an absolute error mean value of 0.0156. Based on the AOD output from the GA-BP neural network, the real-time best AE- BR to improve the inversion accuracy of AECP. Finally, practical tests show that the method achieves accurate inversion of AOD, determines the range of AE-BR from 20-50sr, realizes real-time dynamic correction of AECP, and has strong generalization ability and applicability in practical situations.
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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
Sinomenine (SIN), the alkaloid monomer extracted from Sinomenium acutum, is a kind of non-steroidal anti-inflammatory drug widely used in China to treat rheumatoid arthritis (RA) and various glomerular diseases. It has various pharmacological effects such as anti-inflammatory, analgesic, and anti-tumor. As a strong histamine-releasing agent, SIN has drawn increasing attention in regards to its side effects such as allergic, gastrointestinal, and circulatory systemic reactions. In this report, we first described a patient with primary membranous nephropathy (PMN) who was treated with oral intake of SIN and developed medicine-induced toxic epidermal necrolysis (TEN) and subsequently died of septic multi-organ failure. The present case report intends to demonstrate the underestimated side effects of SIN that can eventually lead to death.
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Two previously undescribed phloroglucinol derivatives [(±) evolephloroglucinols A and B], five unusual coumarins [evolecoumarins A and B and (±) evolecoumarins C-E], and one novel enantiomeric quinoline-type alkaloid [(±) evolealkaloid A], along with 20 known compounds, were isolated from the EtOH extract of the roots of Evodia lepta Merr. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of the undescribed compounds were determined by X-ray diffraction or computational calculations. Their anti-neuroinflammatory effects were assayed. Among the identified compounds, compound 5a effectively reduced nitric oxide (NO) production with an EC50 value of 22.08 ± 0.46 µM. Hence, it could indeed inhibit the lipopolysaccharide (LPS)-induced Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome.
Assuntos
Alcaloides , Evodia , Rutaceae , Evodia/química , Cumarínicos/farmacologia , Cumarínicos/química , Floroglucinol/farmacologia , Floroglucinol/química , Alcaloides/farmacologia , Estrutura Molecular , Óxido NítricoRESUMO
Seven pairs of undescribed enantiomeric bis-coumarins, (±)-dievodialetins A-G, were separated from the roots of Evodia lepta Merr. Two coumarin nuclei were linked via a 1,4-dimethyl4-vinylcyclohexene moiety in (±)-dievodialetins C-G. The structures of the undescribed compounds, including their absolute configurations were elucidated by spectroscopic analyses, X-ray diffraction, and computational calculations. In the biosynthetic pathways, these bis-coumarins were presumably derived from the precursors demethylsuberosin and 3-(3-methylbut-2-enyl)umbelliferone via a [4 + 2] Diels-Alder reaction. Besides, all compounds exhibited neuroprotective effects by inhibiting acetylcholinesterase (AChE) activity with IC50 values ranging from 7.3 to 12.1 nM and they also suppressed oxidative stress (MDA and SOD) and neuroinflammation (IL-1ß and IL-6).
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Evodia , Rutaceae , Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Cumarínicos/farmacologia , Estrutura Molecular , Raízes de Plantas/metabolismo , Rutaceae/metabolismoRESUMO
OBJECTIVE: To investigate the integrated effects of adipocytes on rat beta-cells, differentiated 3T3L1 adipocytes and rat islet cells co-culture system was established. METHODS: There were two groups: control group (SD rat islet cells) and co-culture group (islet cells and 3T3L1 adipocytes coculture system). Islet cells were obtained for determination of (1) insulin secretion and insulin content; (2) mRNA expressions of GLUT2, GCK and Kir6.2; (3) protein expressions of IR-beta, IRS-1 and their tyrosine phosphorylation level. RESULTS: (1) At low glucose, insulin secretion of co-culture group increased compared with that of control group (0.79 +/- 0.35) ng x h(-1) x ml(-1) islet vs. (0.38 +/- 0.09) ng x h(-1) x ml(-1) x islet, P = 0.028. At high glucose, insulin secretion of those two groups was almost at the same level (P = 0.760). Compared with control group (2.84 +/- 0.92), stimulation index (SI, insulin release at high glucose/ low glucose) of co-culture system decreased to (1.57 +/- 0.61, P = 0.04). And the insulin content of the both groups was almost at the same level (P = 0.102). (2) The mRNA of GCK, GLUT2 and Kir6.2 in co-culture group downregulated to (0.27 +/- 0.11, P = 0.01), (0.34 +/- 0.24, P = 0.009) and (0.41 +/- 0.09, P = 0.003) compared with control group (mRNA = 1). (3) The protein levels of IR-beta, IRS-1 and their tyrosine phosphorylation decreased in co-culture system. CONCLUSIONS: 3T3L1 adipocytes are involved in beta-cell dysfunction, which may facilitate the development of type 2 diabetes. The effects may be mediated by multiple pathways, which include downregulation of GSIS related gene expressions and suppression of islet cell insulin signaling.
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Adipócitos/metabolismo , Ilhotas Pancreáticas/metabolismo , Células 3T3-L1 , Adipócitos/citologia , Animais , Técnicas de Cocultura , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/citologia , Camundongos , Canais de Potássio/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
The flower of Hibiscus syriacus Linn is a well-known traditional Chinese medicine (TCM) and health food in China, which has been used to treat dysentery, vaginal discharge, and hemorrhoids. In this study, five polyphenols (compounds 1-5) and five fatty acids (compounds 6-10) were isolated from the ethanol extract of the flower of H. syriacus. The isolated compounds were characterized by spectroscopic techniques. Polyphenols, an important type of natural product, have variety of biological activities. Here, we employed LPS or H2O2-treated SH-SY5Y cell models to test the neuroprotective effect of compounds 1-10. Results found compounds 1-5 (concentration range was around 20 µM on LPS model, concentration range was around 13 µM on H2O2 model), not compounds 6-10, exhibited neuroprotective effect in LPS or H2O2-treated SH-SY5Y cell. PCR analysis showed that compounds 1-5 can effectively improve the mRNA expression of synapse-related gene and neurotrophic factors (Syp, NGF and BDNF) in LPS-treated SH-SY5Y cell. In addition, compounds 1-5 decreased the levels of ROS and MDA and increased the activities of SOD, GSH-Px and CAT in LPS-treated SH-SY5Y cell. Furthermore, compounds 1-5 inhibited neuroinflammation (TNF-α, IL-1ß and IL-6) in LPS-treated SH-SY5Y cell. In conclusion, the polyphenols in the flower of H. syriacus could be a promising candidate for preventive effect of neuroinflammation.
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Anti-Inflamatórios/farmacologia , Flores/química , Hibiscus/química , Neurite (Inflamação)/tratamento farmacológico , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Citocinas/antagonistas & inibidores , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Humanos , Lipopolissacarídeos , Fatores de Crescimento Neural/biossíntese , Fatores de Crescimento Neural/genética , Neurite (Inflamação)/induzido quimicamente , Neurite (Inflamação)/patologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/química , RNA Mensageiro/biossíntese , RNA Mensageiro/genéticaRESUMO
Aims. To examine the association between 4 single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors δ (PPARδ) polymorphisms and C-reactive protein (CRP) level and additional gene-gene interaction. Methods. Line regression analysis was performed to verify polymorphism association between SNP and CRP levels. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction. Results. A total of 1028 subjects (538 men, 490 women) were selected. The carriers of the C allele (TC or CC) of rs2016520 were associated with a significant decreased level of CRP, regression coefficients was -0.338, and standard error was 0.104 (p = 0.001). The carriers of the G allele (CG or GG) of rs9794 were also significantly associated with decreased level of CRP, regression coefficients was -0.219, and standard error was 0.114 (p = 0.012). We also found a potential gene-gene interaction between rs2016520 and rs9794. Subjects with rs2016520-TC or CC, rs9794-CG or GG genotypes have lowest CRP level, difference (95% CI) = -0.50 (-0.69 to -0.21) (p < 0.001), compared to subjects with rs2016520-TT and rs9794-CC genotypes. Conclusions. rs2016520 and rs9794 minor allele of PPARδ and combined effect between the two SNP were associated with decreased CRP level.
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OBJECTIVE: To investigate the effects of the carboxyl end of osteogenic growth peptide (OGP)-OGP((10-14)) and its derivative G38I on the proliferation and differentiation of osteoblasts (OBs). METHODS: Osteoblasts were isolated from the calvariae of newborn SD rats and cultured to G3. OGP((10-14)) or G38I of the concentrations of 10(-15) to 10(-7) mol/L were added to culture medium for 48 hours respectively. The number of cells was counted and MTT analysis was used to examine the proliferation of the cells. The ultrastructure of cells was investigated by electron microscopy. The osteoblasts of G3 were divided into experimental groups, treated with OGP((10-14)) or G38I of the concentration of 10(-11) mol/L for 48 hours, and control group. The alkaline phosphatase activity in the culture medium was measured. The protein expression level of type-I collagen was evaluated by immunohistochemistry. The core binding factor 1 (Cbfa1) and type-I collagen mRNA level of osteoblasts were determined by RT-PCR. RESULTS: With a biphasic effect on, OGP((10-14)) and G38I stimulated the number enhancement of OBs dose-dependently at low concentration and inhibited it at high concentration. The numbers of OB were the highest (37 x 10(4)/ml +/- 7 x 10(4)/ml and 30 x 10(4)/ml +/- 5 x 10(4)/ml respectively) when treated by OGP((10-14)) or G38I of the concentration of 10(-11)mol/L. The rough endoplasm net was flourishing and the secreting vesicle was abounding in the experimental cells. There was calcium crystal in the control cells. The activity of alkaline phosphatase in the culture medium of the OGP (10(-14)) and G38I groups were higher than that in the control group (4.47 U/g and 3.82 U/g vs 2.21 U/g). The protein expression level of type-I collagen was higher and the mRNA levels of Cbfa1 and type-I collagen were higher in the OGP((10-14)) and G38I groups were increased in the experimental groups in comparison with the control group (P < 0.05, P < 0.01, and P < 0.05). CONCLUSION: They stimulated cell number enhancement dose dependently at low concentration and followed by inhibition at high concentration. Just as the native OGP, OGP((10-14)) and its derivative G38I stimulate the proliferation of osteoblasts, and improve their activity, up-regulate the Cbfa1 and type-I collagen mRNA expression levels and increase the collagen synthesis, thus promoting the differentiation and osteogenic effect of osteoblasts.
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Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Histonas/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Osteoblastos/citologia , Fosfatase Alcalina/metabolismo , Animais , Animais Recém-Nascidos , Dióxido de Carbono/farmacologia , Células Cultivadas , Colágeno Tipo I/biossíntese , Colágeno Tipo I/genética , Subunidades alfa de Fatores de Ligação ao Core/biossíntese , Subunidades alfa de Fatores de Ligação ao Core/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the distribution of tetracycline-arginine-glycine-aspartate-tyrosine (T-RGDY) in mice and its effect on bone. METHODS: 125-labeled T-RGDY was studied for its distribution in mice and for its effects on bone by histomorphometry in ovariectomized rats. RESULTS: The 125I-labeled T-RGDY was more concentrated in the osteoporotic bone than in the normal bone. Compared with ovariectomy group, the morphologic index such as trabecular bone volume/total tissue volume (TBV/TTV), TBV/sponge bone volume (SBV), and mean trabecular plate thickness (MTPT) in T-RGDY group significantly increased (P < 0.05). As compared with sham operation group, MTPT significantly increased in T-RGDY group (P < 0.05), while TBV/SBV and mean trabecular plate density significantly decreased (P < 0.05), and TBV/TYV and mean trabecular plate spacing were almost the same as those in sham operation group (P > 0.05). CONCLUSION: T-RGDY may concentrate in bone tissue to a certain degree, which is closely related with the status of bone remodeling. T-RGDY may inhibit the bone loss caused by ovariectomy.
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Oligopeptídeos/farmacocinética , Osteoporose/metabolismo , Tetraciclina/farmacocinética , Tirosina/farmacocinética , Animais , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Feminino , Camundongos , Oligopeptídeos/farmacologia , Osteoporose/prevenção & controle , Ovariectomia , Ratos , Ratos Sprague-Dawley , Tetraciclina/farmacologia , Distribuição Tecidual , Tirosina/farmacologiaRESUMO
BACKGROUND: Prostate cancer represents the leading cause of male death across the world. A recent genome-wide association study (GWAS) identified five novel susceptibility loci for prostate cancer in the Japanese population. This study is to replicate and fine map the potential association of these five loci with prostate cancer in the Chinese Han population. METHODS: In Phase I of the study, we tested the five single nucleotide polymorphisms (SNPs) which showed the strongest association evidence in the original GWAS in Japanese. The study sample consists of 1,169 Chinese Hans, comprising 483 patients and 686 healthy controls. Then in phase II, flanking SNPs of the successfully replicated SNPs in Phase I were genotyped and tested for association with prostate cancer to fine map those significant association signals. RESULTS: We successfully replicated the association of rs13385191 (located in the C2orf43 gene, Pâ=â8.60×10(-5)), rs12653946 (Pâ=â1.33×10(-6)), rs1983891 (FOXP4, Pâ=â6.22×10(-5)), and rs339331 (GPRC6A/RFX6, Pâ=â1.42×10(-5)) with prostate cancer. The most significant odds ratio (OR) was recorded as 1.41 (95% confidence interval 1.18-1.68) for rs12653946. Rs9600079 did not show significant association (Pâ=â8.07×10(-2)) with prostate cancer in this study. The Phase II study refined these association signals, and identified several SNPs showing more significant association with prostate cancer than the very SNPs tested in Phase I. CONCLUSIONS: Our results provide further support for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in Eastern Asian populations. This study also characterized the novel loci reported in the original GWAS with more details. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.