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1.
Planta ; 259(2): 50, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285114

RESUMO

MAIN CONCLUSION: The oxidosqualene cyclases (OSCs) generating triterpenoid skeletons in Cyclocarya paliurus were identified for the first time, and two uridine diphosphate (UDP)-glycosyltransferases (UGTs) catalyzing the glycosylation of flavonoids were characterized. Cyclocarya paliurus, a native rare dicotyledonous plant in China, contains an abundance of triterpenoid saponins and flavonoid glycosides that exhibit valuable pharmaceutical effects in preventing hypertension, hyperlipidemia, and diabetes. However, the molecular mechanism explaining the biosynthesis of triterpenoid saponin and flavonoid glycoside in C. paliurus remains unclear. In this study, the triterpene content in different tissues and the expression pattern of genes encoding the key enzymes associated with triterpenoid saponin and flavonoid glycoside biosynthesis were studied using transcriptome and metabolome analysis. The eight upstream oxidosqualene cyclases (OSCs) involved in triterpenoid saponin biosynthesis were functionally characterized, among them CpalOSC6 catalyzed 2,3;22,23-dioxidosqualene to form 3-epicabraleadiol; CpalOSC8 cyclized 2,3-oxidosqualene to generate dammarenediol-II; CpalOSC2 and CpalOSC3 produced ß-amyrin and CpalOSC4 produced cycloartenol, while CpalOSC2-CpalOSC5, CpalOSC7, and CpalOSC8 all produced lanosterol. However, no catalytic product was detected for CpalOSC1. Moreover, two downstream flavonoid uridine diphosphate (UDP)-glycosyltransferases (UGTs) (CpalUGT015 and CpalUGT100) that catalyze the last step of flavonoid glycoside biosynthesis were functionally elucidated. These results uncovered the key genes involved in the biosynthesis of triterpenoid saponins and flavonoid glycosides in C. paliurus that could be applied to produce flavonoid glycosides and key triterpenoid saponins in the future via a synthetic strategy.


Assuntos
Saponinas , Esqualeno/análogos & derivados , Triterpenos , Glicosídeos , Flavonoides , Saponinas/genética , Glicosiltransferases , Difosfato de Uridina
2.
J Org Chem ; 87(6): 4263-4272, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35234478

RESUMO

Heterocyclic compounds, especially oxygen-containing heterocyclic compounds, are crucial moieties in bioactive compounds and drug leads. Substituted chroman-4-ones are a kind of the most significant structural skeletons. Herein, we report a visible-light-induced dual acylation of alkenes for constructing 3-substituted chroman-4-ones, which undergoes a radical tandem cyclization reaction through carbon-carbon bond cleavage of oxime esters by a nitrogen-centered radical strategy. A series of 3-substituted chroman-4-ones were prepared with up to 86% yield.


Assuntos
Alcenos , Compostos Heterocíclicos , Acilação , Alcenos/química , Carbono/química , Cromanos , Ciclização , Compostos Heterocíclicos/química
3.
Stem Cells ; 38(2): 218-230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31648394

RESUMO

Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene that results in the production of neurotoxic mutant HTT (mHTT) protein. Suppressing HTT production with antisense oligonucleotides (ASOs) is a promising treatment strategy for HD; however, the difficulty of delivering ASOs to deep brain structures is a major barrier for its clinical application. The glymphatic system of astrocytes involving aquaporin 4 (AQP-4) controls the entry of macromolecules from the cerebrospinal fluid into the brain. Mesenchymal stem cells (MSCs) target astrocytes to inhibit neuroinflammation. Here we examined the glymphatic distribution of ASO in the brain and the therapeutic potential of combining intravenously injection of mesenchymal stem cells (IV-MSC) and ASOs for the treatment of HD. Our results show that Cy3-labeled ASOs entered the brain parenchyma via the perivascular space following cisternal injection, but the brain distribution was significantly lower in AQP-4-/- as compared with wild-type mice. Downregulation of the AQP-4 M23 isoform was accompanied by decreased brain levels of ASOs in BACHD mice as well as an increase in astrogliosis and phosphorylation of nuclear factor κB (NF-κB) p65. IV-MSC treatment restored AQP-4 M23 expression, attenuated astrogliosis, and decreased NF-κB p65 phosphorylation; it also increased the brain distribution of ASOs and enhanced the suppression of mHTT in BACHD mice. These results suggest that modulating glymphatic activity using IV-MSC is a novel strategy for improving the potency of ASO in the treatment of HD.


Assuntos
Aquaporina 4/metabolismo , Doença de Huntington/genética , Células-Tronco Mesenquimais/metabolismo , Oligonucleotídeos Antissenso/genética , Adulto , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Pessoa de Meia-Idade
4.
J Neuroinflammation ; 17(1): 347, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213462

RESUMO

BACKGROUND: The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson's disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. METHODS: In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. RESULTS: Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1ß (IL-1ß) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. CONCLUSIONS: These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.


Assuntos
Microbioma Gastrointestinal/fisiologia , Imunidade/fisiologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/imunologia , Microglia/imunologia , Doenças Neurodegenerativas/imunologia , Porphyromonas gingivalis/imunologia , Administração Oral , Animais , Infecções por Bacteroidaceae/genética , Infecções por Bacteroidaceae/imunologia , Células Cultivadas , Neurônios Dopaminérgicos/imunologia , Neurônios Dopaminérgicos/microbiologia , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Camundongos , Camundongos Transgênicos , Microglia/microbiologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/microbiologia , Permeabilidade , Substância Negra/imunologia , Substância Negra/microbiologia
5.
Prep Biochem Biotechnol ; 50(7): 682-688, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069137

RESUMO

Stemonae Radix, a medicinal and edible herb, has been reported to possess various pharmacological effects. In the present study, Stemonae Radix was fermented by fungi to improve the antioxidant and anti-tyrosinase activities. The results showed that Stemonae Radix fermented by Mucor circinelloides T2-12 exhibited two-folds more antioxidant and anti-tyrosinase activities than non-fermented material. The increased activity might be ascribed to the improvement of total phenolic content, hydrolyzation of glucosides and esters of phenolics and metabolism of saccharides according to ultraviolet and nuclear paramagnetic resonance spectroscopy. This paper suggested that fermenting Stemonae Radix with M. circinelloides T2-12 is effective to increase antioxidant and anti-tyrosinase effects and Stemonae Radix fermented by M. circinelloides T2-12 might be newly alternative of natural antioxidant and tyrosinase inhibitor. The present study is the first to report that pure strain fermentation processing is effective in improving the antioxidant and anti-tyrosinase activities of Stemonae Radix.


Assuntos
Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Mucor/metabolismo , Stemonaceae/química , Cátions , Ésteres , Fermentação , Glucosídeos/química , Hidrólise , Espectroscopia de Ressonância Magnética , Medicina Tradicional Chinesa , Fenóis , Extratos Vegetais/farmacologia , Raízes de Plantas/metabolismo , Compostos de Espiro , Raios Ultravioleta
6.
BMC Plant Biol ; 19(1): 451, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655543

RESUMO

BACKGROUND: Taproot thickening is a complex biological process that is dependent on the coordinated expression of genes controlled by both environmental and developmental factors. Panax notoginseng is an important Chinese medicinal herb that is characterized by an enlarged taproot as the main organ of saponin accumulation. However, the molecular mechanisms of taproot enlargement are poorly understood. RESULTS: A total of 29,957 differentially expressed genes (DEGs) were identified during the thickening process in the taproots of P. notoginseng. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment revealed that DEGs associated with "plant hormone signal transduction," "starch and sucrose metabolism," and "phenylpropanoid biosynthesis" were predominantly enriched. Further analysis identified some critical genes (e.g., RNase-like major storage protein, DA1-related protein, and Starch branching enzyme I) and metabolites (e.g., sucrose, glucose, fructose, malate, and arginine) that potentially control taproot thickening. Several aspects including hormone crosstalk, transcriptional regulation, homeostatic regulation between sugar and starch, and cell wall metabolism, were identified as important for the thickening process in the taproot of P. notoginseng. CONCLUSION: The results provide a molecular regulatory network of taproot thickening in P. notoginseng and facilitate the further characterization of the genes responsible for taproot formation in root medicinal plants or crops.


Assuntos
Redes Reguladoras de Genes , Metaboloma , Panax notoginseng/genética , Proteínas de Plantas/metabolismo , Transdução de Sinais , Transcriptoma , Regulação da Expressão Gênica de Plantas , Panax notoginseng/crescimento & desenvolvimento , Panax notoginseng/fisiologia , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/fisiologia
7.
J Asian Nat Prod Res ; 21(7): 673-678, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29749266

RESUMO

A new menthane-type monoterpenoid, illigerate E (1), as well as two known ones, (1R*,3R*,4S*,6R*)-6,8-dihydroxymenthol (2) and cis-4-hydroxy-5-(1-hydroxy-1-methylethyl)-2-methyl-2-cyclohexene-1-one (3), were isolated from fermented Illigera aromatica with Clonostachys rogersoniana 828H2. Their structures were identified by HRESIMS and 1D/2D NMR spectra. Their inhibitory effects of NO production in RAW 264.7 macrophages were estimated.


Assuntos
Hernandiaceae/química , Hypocreales/química , Monoterpenos/química , Monoterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Fermentação , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Espectrometria de Massas por Ionização por Electrospray
8.
Anal Bioanal Chem ; 409(21): 4951-4958, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28660339

RESUMO

We report a highly sensitive and selective strategy for Cd(II) assay using a singly labeled multifunctional probe consisting of a Cd(II)-specific aptamer (CAP), which acted as a recognition element for Cd(II) and a signal reporter. The presence of Cd(II) can induce the conformational switching of the CAP, accompanied by a change in fluorescence intensity. Thereby, a fluorescence strategy for Cd(II) assay was established. The proposed method has a detection limit of 2.15 nM, which is much lower than the detection limits reported in related literature. This strategy involves only an aptamer probe, and the use of such a G4-based quencher avoids the dual labeling of the CAP with fluorophore/quencher units. It is obviously more convenient and economical than the other aptamer-based biosensors for Cd(II) detection. The mechanism by which Cd(II) induces the CAP to change from a random coil sequence to a stem-loop structure was studied in a series of control experiments. This strategy would be helpful in the design of a sensitive analytical platform for various target assays in environmental and biomedical fields. Graphical Abstract The presence of Cd2+ leads to the conformational change of CAP from a random coil sequence to a stem-loop structure, resulting in a quenching in the fluorescence.

9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(5): 736-739, 2017 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-29130667

RESUMO

OBJECTIVE: To evaluate pregnancy outcomes of multiparae in women with advanced age (≥35 yr.) after the 2008 Wenchuan earthquake. METHODS: Clinical data of 542 pregnant women with prenatal care in Wenchuan during 20082013 were reviewed,comparing preconception conditions,pregnant rates,pregnant complications,and perinatal outcomes between those younger ( n=176) and older ( n=366) than 35 years. RESULTS: In the 542 women,622 conceptions were reported,with 517 deliveries and 522 live births. The women with advanced age had lower cumulative pregnancy rate (twoyear),higher incidence of hypertensive disorders of pregnancy,gestational diabetes,multiple pregnancy,fetal distress,low birth weight and birth defects than their younger counterparts. The younger women also had higher term live birth rate and lower miscarriage rate. But the differences showed no statistical significance. CONCLUSION: Prenatal care brings similar pregnant outcomes to multiparae in women with advance aged and younger aged.


Assuntos
Terremotos , Idade Materna , Complicações na Gravidez , Resultado da Gravidez , Adulto , China , Desastres , Feminino , Humanos , Gravidez , Taxa de Gravidez
10.
J Insect Sci ; 16(1)2016.
Artigo em Inglês | MEDLINE | ID: mdl-27623751

RESUMO

To better understand the olfactory receptive mechanisms involved in host selection and courtship behavior of Sitodiplosis mosellana (Diptera: Cecidomyiidae), one of the most important pests of wheat, scanning and transmission electron microscopy were used to examine the external morphology and ultrastructure of the antennal sensilla. The moniliform antennae exhibit obvious sexual dimorphism: antennae of the males are markedly longer than those of the females. Furthermore, each male flagellomere consists of two globular nodes, whereas each female flagellomere is cylindrical. Seven types of sensilla were identified in both sexes. Two types of s. chaetica have a lumen without dendrites and thick walls, suggesting that they are mechanoreceptors. S. trichodea and s. circumfila are typical chemoreceptors, possessing thin multiporous walls encircling a lumen with multiple dendrites. There are significantly more s. trichodea in female than in male, which may be related to host plant localization. In contrast, male s. circumfila are highly elongated compared to those of females, perhaps for pheromone detection. Peg-shaped s. coeloconica are innervated with unbranched dendrites extending from the base to the distal tip. Type 1 s. coeloconica, which have deep longitudinal grooves and finger-like projections on the surface, may serve as olfactory or humidity receptors, whereas type 2 s. coeloconica, smooth with a terminal pore, may be contact chemoreceptors. Also, this is the first report of Böhm' bristles at proximal scape on antennae of Cecidomyiid species potentially functioning as mechanoreceptors.


Assuntos
Dípteros/ultraestrutura , Animais , Antenas de Artrópodes/ultraestrutura , Dípteros/fisiologia , Feminino , Masculino , Mecanorreceptores/ultraestrutura , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Percepção Olfatória , Sensilas/ultraestrutura , Caracteres Sexuais
11.
J Asian Nat Prod Res ; 18(6): 603-10, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26744060

RESUMO

A new C20-diterpenoid alkaloid handelidine (1) and twenty-seven known alkaloids (2-28) were isolated from the roots of Aconitum handelianum. Their structures were established on the basis of extensive spectroscopic analyses. The study indicated that denudatine-type C20-diterpenoid alkaloids with vicinal-triol system and benzyltetrahydroisoquinoline alkaloids exhibited significant antioxidant activities measured by three antioxidant test systems. The aconitine-type C19-diterpenoid alkaloids could serve as potential secondary antioxidants for their strong binding effects to metal ions.


Assuntos
Aconitum/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Aconitina/química , Alcaloides/química , Antioxidantes/química , Diterpenos/química , Medicamentos de Ervas Chinesas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oxirredução , Raízes de Plantas/química
12.
Clin Invest Med ; 38(4): E173-84, 2015 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-26278427

RESUMO

PURPOSE: Our study is designed to examine the diagnostic performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for bladder cancers (BC), and to determine whether DW-MRI can differentiate muscle invasive bladder cancer (MIBC) from non-MIBC (NMIBC). METHODS: A meta-analysis was performed of published studies that investigated the performance of DW-MRI for BC. These studies were retrieved from scientific literature databases using sensitive electronic search strategies. The STATA 12.0 and Meta-disc software were employed for statistical analyses of data extracted from selected studies. RESULTS: Our search initially returned 230 articles, of which 11 met the inclusion criteria and were enrolled into the final meta-analysis. Five of the included studies reported the diagnostic performance of DW-MRI for BC with a cumulative total of 243 BC patients and 82 healthy subjects. Eight studies investigated the diagnostic performance of DW-MRI for differentiating MIBC from NMIBC, involving 259 MIBC lesions and 515 NMIBC lesions. Meta-analysis results were as follows: the diagnostic performance of DW-MRI for BC (sensitivity: 0.95 [0.75-0.99]; specificity: 0.85 [0.74-0.92]; positive likelihood ratio: 6.45 [3.64-11.42]; negative likelihood ratio: 0.055 [0.009-0.333]; diagnostic odds ratio: 117.11 [19.37-708.05]; area under the curve (AUC): 0.91); the diagnostic performance of DW-MRI to differentiate MIBC from NMIBC (sensitivity: 0.85 [0.76 - 0.91]; specificity: 0.90 [0.87 - 0.93]; positive likelihood ratio:8.81[6.43 - 12.07]; negative likelihood ratio: 0.16 [0.10 - 0.28]; diagnostic odds ratio: 53.95 [25.68 - 113.33]; AUC: 0.92). CONCLUSION: DW-MRI has an outstanding diagnostic performance, with advanced sensitivity and specificity, for imaging of bladder cancers and for differentiating MIBC from NMIBC.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias da Bexiga Urinária/diagnóstico , Humanos , Sensibilidade e Especificidade , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(10): 2785-91, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25739226

RESUMO

A series of 354 polyester-cotton blend fabrics were studied by the near-infrared spectra (NIRS) technology, and a NIR qualitative analysis model for different spectral characteristics was established by partial least squares (PLS) method combined with qualitative identification coefficient. There were two types of spectrum for dying polyester-cotton blend fabrics: normal spectrum and slash spectrum. The slash spectrum loses its spectral characteristics, which are effected by the samples' dyes, pigments, matting agents and other chemical additives. It was in low recognition rate when the model was established by the total sample set, so the samples were divided into two types of sets: normal spectrum sample set and slash spectrum sample set, and two NIR qualitative analysis models were established respectively. After the of models were established the model's spectral region, pretreatment methods and factors were optimized based on the validation results, and the robustness and reliability of the model can be improved lately. The results showed that the model recognition rate was improved greatly when they were established respectively, the recognition rate reached up to 99% when the two models were verified by the internal validation. RC (relation coefficient of calibration) values of the normal spectrum model and slash spectrum model were 0.991 and 0.991 respectively, RP (relation coefficient of prediction) values of them were 0.983 and 0.984 respectively, SEC (standard error of calibration) values of them were 0.887 and 0.453 respectively, SEP (standard error of prediction) values of them were 1.131 and 0.573 respectively. A series of 150 bounds samples reached used to verify the normal spectrum model and slash spectrum model and the recognition rate reached up to 91.33% and 88.00% respectively. It showed that the NIR qualitative analysis model can be used for identification in the recycle site for the polyester-cotton blend fabrics.

14.
Nat Prod Res ; : 1-7, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39371032

RESUMO

Gardeniae Fructus, the dried fruit of Gardenia jasminoides, was fermented with Aspergillus niger DQWM-G11. The antibacterial activities of the fermented and non-fermented products were measured and the transformation of chemical constituents was detected. The results revealed that A. niger DQWM-G11 fermented Gardeniae Fructus (AFGF) possessed a stronger antibacterial effect with a minimal inhibitory concentration (MIC) value of 256 µg/mL, compared to the raw material (MIC: > 1024 µg/mL). An undescribed microbial transformation reaction was discovered, where geniposide (1) was transformed into 1ß-methoxyl-4-epigardendiol (2), which was then verified. The produced component exhibited a stronger antibacterial effect (MIC: 256 µg/mL) than raw geniposide (1) (MIC: >1024 µg/mL), indicating that the increased activity of Gardeniae Fructus was due to the biotransformation. The discovery of this microbial transformation reaction will provide an important theoretical basis for further developing and applying Gardeniae Fructus and geniposide.

15.
Front Plant Sci ; 13: 883818, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693187

RESUMO

The genus Panax is a valuable natural medicinal source used worldwide that contains high levels of triterpenoid saponins with extensive pharmacological activities. In past decades, molecular biotechnology and breeding techniques have been respectively used to generate omics data and information on cultivars primarily from Panax ginseng (ginseng), Panax quinquefolium (American ginseng), and Panax notoginseng (Sanqi) to biosynthesize valuable saponins, improve product quality, and conduct cost-controlled cultivation. Although much data have been produced, there are concerns that redundant data might be generated and that relatively scattered data might be overlooked. Therefore, many scientists desire a reliable, comprehensive omics database of the Panax genus that could save time and promote integrated analysis. Therefore, to provide all-inclusive, reliable, and valuable information on the Panax genus, PanaxGDB, an open comprehensive database that integrates data on omics and information on varieties, was established. The database contains information on nearly 600 compounds from 12 Panax species, draft genomic sequences with annotations and gene expression levels, single nucleotide polymorphisms, genome-wide association analysis based on agronomic traits, globally collected germplasm information, summaries, omics data of the Panax genus, and online versatile analytic tools. The Panax genus database will be updated when new data are released to continue serving as a central portal to boost research on the biology and functions of Panax. PanaxGDB is available at: http://panaxGDB.ynau.edu.cn.

16.
Insect Sci ; 27(2): 292-303, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30156035

RESUMO

Juvenile hormone (JH), a growth regulator, inhibits ecdysteroid-induced metamorphosis and controls insect development and diapause. Methoprene-tolerant (Met) and Krüppel homolog 1 (Kr-h1) are two proteins involved in JH action. To gain some insight into their function in development of Sitodiplosis mosellana, an insect pest undergoing obligatory larval diapause at the mature 3rd instar stage, we cloned full-length complementary DNAs of Met and Kr-h1 from this species. SmMet encoded a putative protein, which contained three domains typical of the bHLH-PAS family and eight conserved amino acid residues important for JH binding. SmKr-h1 encoded a protein showing high sequence homology to its counterparts in other species, and contained all eight highly conserved Zn-finger motifs for DNA-binding. Expression patterns of SmMet and SmKr-h1 were developmentally regulated and JH III responsive as well. Their mRNA abundance increased as larvae entered early 3rd instar, pre-diapause and maintenance stages, and peaked during post-diapause quiescence, a pattern correlated with JH titers in this species. Different from reduced expression of SmMet, SmKr-h1 mRNA increased at mid-to-late period of post-diapause development. Topical application of JH III on diapausing larvae also induced the two genes in a dose-dependent manner. Expression of SmMet and SmKr-h1 clearly declined in the pre-pupal phase, and was significantly higher in female adults than male adults. These results suggest that JH-responsive SmMet and SmKr-h1 might play key roles in diapause induction and maintenance as well as in post-diapause quiescence and adult reproduction, whereas metamorphosis from larvae to pupae might be correlated with their reduced expression.


Assuntos
Culicomorfos/genética , Proteínas de Insetos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Culicomorfos/crescimento & desenvolvimento , Culicomorfos/metabolismo , Diapausa de Inseto , Proteínas de Drosophila , Feminino , Proteínas de Insetos/metabolismo , Hormônios Juvenis/metabolismo , Fatores de Transcrição Kruppel-Like , Masculino
17.
Stem Cell Res Ther ; 11(1): 222, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513306

RESUMO

BACKGROUND: Machado-Joseph disease is the most common autosomal dominant hereditary ataxia worldwide without effective treatment. Mesenchymal stem cells (MSCs) could slow the disease progression, but side effects limited their clinical application. Besides, MSC-derived exosomes exerted similar efficacy and have many advantages over MSCs. The aim of this study was to examine the efficacy of MSC-derived exosomes in YACMJD84.2 mice. METHODS: Rotarod performance was evaluated every 2 weeks after a presymptomatic administration of intravenous MSC-derived exosomes twice in YACMJD84.2 mice. Loss of Purkinje cells, relative expression level of Bcl-2/Bax, cerebellar myelin loss, and neuroinflammation were assessed 8 weeks following treatment. RESULTS: MSC-derived exosomes were isolated and purified through anion exchange chromatography. Better coordination in rotarod performance was maintained for 6 weeks in YACMJD84.2 mice with exosomal treatment, compared with those without exosomal treatment. Neuropathological changes including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation were also attenuated 8 weeks after exosomal treatment. The higher relative ratio of Bcl-2/Bax was consistent with the attenuation of loss of Purkinje cells. CONCLUSIONS: MSC-derived exosomes could promote rotarod performance and attenuate neuropathology, including loss of Purkinje cells, cerebellar myelin loss, and neuroinflammation. Therefore, MSC-derived exosomes have a great potential in the treatment of Machado-Joseph disease.


Assuntos
Exossomos , Doença de Machado-Joseph , Células-Tronco Mesenquimais , Animais , Cerebelo , Modelos Animais de Doenças , Doença de Machado-Joseph/genética , Camundongos
18.
Sci Rep ; 10(1): 16225, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004823

RESUMO

Duane retraction syndrome (DRS) is a neuromuscular dysfunction of the eyes. Although many causative genes of DRS have been identified in Europe and the United States, few reports have been published in regard to Chinese DRS. The aim of the present study was to explore the genetic defect of DRS in a Chinese family. Exome sequencing was used to identify the disease-causing gene for the two affected family members. Ophthalmic and physical examinations, as well as genetic screenings for variants in chimerin 1 (CHN1), were performed for all family members. Functional analyses of a CHN1 variant in 293T cells included a Rac-GTP activation assay, α2-chimaerin translocation assay, and co-immunoprecipitation assay. Genetic analysis revealed a NM_001822.7: c.637T > G variant in the CHN1 gene, which resulted in the substitution of a highly conserved C1 domain with valine at codon 213 (NP_001813.1: p.(Phe213Val)) (ClinVar Accession Number: SCV001335305). In-silico analysis revealed that the p.(Phe213Val) substitution affected the protein stability and connections among the amino acids of CHN1 in terms of its tertiary protein structure. Functional studies indicated that the p.(Phe213Val) substitution reduced Rac-GTP activity and enhanced membrane translocation in response to phorbol-myristoyl acetate (PMA). Together with previous studies, our present findings demonstrate that CHN1 may be an important causative gene for different ethnicities with DRS.


Assuntos
Povo Asiático/genética , Quimerina 1/genética , Síndrome da Retração Ocular/genética , Mutação de Sentido Incorreto , Adolescente , Adulto , Criança , Síndrome da Retração Ocular/patologia , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto Jovem
19.
J Med Ultrason (2001) ; 46(1): 129-135, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30327989

RESUMO

PURPOSE: To investigate the relationship of femoral head coverage (FHC) with Graf's classification for diagnosis of developmental dysplasia of the hip (DDH) and its role in evaluating hip stability. METHODS: A total of 4222 hips were screened ultrasonographically with Graf's and Harcke's methods. The stability of hips was analyzed using the difference between FHCs at neutral and flexion positions (FHC-D). RESULTS: (1) For the non-dislocated hips, the mean value of FHC at the neutral position was 59.4%, which was significantly greater than 55.0% of FHC at the flexion position (p < 0.001). (2) FHC at the neutral position corresponding to Graf I, IIa/b, IIc, D, III, and IV was 63.0 ± 4.7%, 57.0 ± 5.2%, 49.5 ± 5.5%, 37.7 ± 3.7%, 30.2 ± 12.7%, and 7.4 ± 11.9%, respectively, and that at the flexion position was 59.0 ± 4.4%, 50.7 ± 9.4%, 35.2 ± 5.2%, 30.8 ± 1.3%, 23.4 ± 10.7%, and 4.7 ± 9.9%, respectively, showing a statistically significant difference between the two positions. (3) The AUC of FHC-D in evaluating the stability of hips was 0.972. When the threshold was 8.5%, the sensitivity, specificity, and accuracy of FHC-D in detecting hip instability were 89.0%, 93.0%, and 93.9%, respectively. CONCLUSIONS: FHC can be used as a reference indicator for DDH classification. FHC at different positions corresponds to different reference values, and FHC-D can be used as a quantitative indicator for assessment of hip stability.


Assuntos
Luxação Congênita de Quadril/diagnóstico por imagem , Feminino , Luxação Congênita de Quadril/classificação , Luxação Congênita de Quadril/fisiopatologia , Humanos , Lactente , Recém-Nascido , Instabilidade Articular/classificação , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/fisiopatologia , Masculino , Amplitude de Movimento Articular , Sensibilidade e Especificidade , Ultrassonografia/métodos
20.
J Nat Med ; 73(1): 312-317, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30414014

RESUMO

Illigera aromatica S. Z. Huang et S. L. Mo and Illigera henryi W. W. Sm., belonging to the genus Illigera (Hernandiaceae), are used as herbal medicines for promoting blood circulation and treating tuberculosis. Actinodaphnine, the major bioactive alkaloid, plays an important role in the quality controls of the herbs. In the present study, a rapid, simple, accurate, and precise proton quantitative nuclear magnetic resonance (1H-qNMR) method was developed to determine the content of actinodaphnine in I. aromatica and I. henryi. DMSO-d6 enabled satisfactory separation of the signals to be integrated in 1H NMR spectrum. 1,4-Dinitrobenzene was selected as an internal standard. The limits of determination and quantitation were 0.005 and 0.038 mg/mL, respectively. This work implied that 1H-qNMR represents a feasible alternative to HPLC-based methods for quantitation of actinodaphnine in I. aromatica and I. henryi and is suitable for the quality control of I. aromatica and I. henryi.


Assuntos
Plantas Medicinais/química , Espectroscopia de Prótons por Ressonância Magnética/métodos , Prótons
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