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1.
Adv Sci (Weinh) ; 9(13): e2104682, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35240008

RESUMO

Direct cell reprogramming, also called transdifferentiation, is valuable for cell fate studies and regenerative medicine. Current approaches to transdifferentiation are usually achieved by directly targeting the nuclear functions, such as manipulating the lineage-specific transcriptional factors, microRNAs, and epigenetic modifications. Here, a robust method to convert fibroblasts to neurons through targeting the cytoskeleton followed by exposure to lineage-specification surroundings is reported. Treatment of human foreskin fibroblasts with a single molecule inhibitor of the actomyosin contraction, can disrupt the cytoskeleton, promote cell softening and nuclear export of YAP/TAZ, and induce a neuron-like state. These neuron-like cells can be further converted into mature neurons, while single-cell RNA-seq shows the homogeneity of these cells during the induction process. Finally, transcriptomic analysis shows that cytoskeletal disruption collapses the original lineage expression profile and evokes an intermediate state. These findings shed a light on the underestimated role of the cytoskeleton in maintaining cell identity and provide a paradigm for lineage conversion through the regulation of mechanical properties.


Assuntos
Transdiferenciação Celular , Fibroblastos , Diferenciação Celular , Reprogramação Celular , Fibroblastos/fisiologia , Humanos , Neurônios
2.
Signal Transduct Target Ther ; 6(1): 414, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873151

RESUMO

Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 µM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.


Assuntos
Antivirais/administração & dosagem , Azidas/administração & dosagem , COVID-19/tratamento farmacológico , Desoxicitidina/análogos & derivados , SARS-CoV-2/metabolismo , Timo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Coronavirus Humano OC43/metabolismo , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Timo/metabolismo , Timo/virologia
3.
Phytochemistry ; 192: 112935, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34478990

RESUMO

Thirteen compounds were isolated from the lipid-soluble extracts of Illicium ternstroemioides A. C. Smith, including eleven previously undescribed prenylated C6-C3 compounds, a previously undescribed prenylated C6-C3 derivative-abscisic acid ester hybrid, and a known compound (4S)-illicinone I. Their structures and configurations were mainly elucidated by spectroscopic analyses, CD experiments and X-ray crystallography. (2S,4R,11S)-4-O-methyl-12-chloroillifunone C, (2S,4R,11R)-2,3-dihydro-4-O-methyl illioliganfunone D, and illiternfunol A were found to exhibit weak activity against Coxsackievirus B3, with IC50 values ranging from 27.8 to 33.3 µM. Illiternone B exhibited more potent activities against Coxsackievirus B3 and influenza virus A than did its geometric isomer illiternone A, with IC50 values of 7.7 µM and 2.5 µM, respectively. None of these compounds displayed cytotoxic activities.


Assuntos
Illicium , Antivirais/farmacologia , Cristalografia por Raios X , Estrutura Molecular
4.
Phytochemistry ; 189: 112818, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34102590

RESUMO

Eight undescribed humulane-type sesquiterpenoids (xanthspinol A-E, I, J and N), three undescribed germacrane-type sesquiterpenoids (xanthspinol F, G and O) and twelve known compounds were isolated from the fruits of Xanthium spinosum. The structures of the undescribed compounds were elucidated by analyses of spectroscopic data, electronic circular dichroism (ECD) calculations, dimolybdenum tetraacetate [Mo2(OAc)4]-induced circular dichroism (ICD) spectra, a CD exciton chirality method and the modified Mosher's method. Xanthspinol A and B featured a humulane skeleton containing a 2,5-dihydrofuran fragment. Putative biosynthetic pathways for the undescribed compounds are proposed. Xanthspinol N, 8-epi-isoxanthanol and deacetyl-4-epixanthanol showed moderate activity against Coxsackie virus B3 (CVB3) with IC50 values of 8.70, 3.70 and 3.70 µM, respectively.


Assuntos
Sesquiterpenos , Xanthium , Dicroísmo Circular , Frutas , Estrutura Molecular , Sesquiterpenos de Germacrano
5.
Chem Sci ; 12(20): 7003-7011, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-34123328

RESUMO

The construction of libraries of stereoisomers of natural products serves as an important approach to investigating the correlation between the stereostructure and biological activity. However, the total synthesis and isomerzation of polycyclic scaffolds with multiple chrial centers are rare. Spirooliganin (1), a new skeleton natural product isolated from the plant Illicium oligandrum, was structurally characterized by comprehensive analysis of NMR spectroscopic data and ECD which revealed an unprecedented 5-6-6-6-7 polycyclic framework with six chiral centers. Here we report a 17-step total synthesis to prepare a library of stereochemically diverse isomers of spirooliganin, including 16 diastereoisomers and 16 regioisomers. In addition to a regioselective hetero-Diels-Alder cycloaddition, the synthetic strategy involves a photo-induced stereoselective Diels-Alder reaction, which gives only the abnormal trans-fused product as rationalized by density functional theory calculations. Preliminary biological evaluation showed that spirooliganin and regioisomers 39 exhibited potent inhibition of Coxsackievirus B3. It also revealed the pharmacophore effect of the D-ring (16R,18R,24R, and 26R) for their antiviral activities.

6.
Virol Sin ; 36(5): 1154-1164, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34046815

RESUMO

Influenza A viruses (IAV) are responsible for seasonal flu epidemics, which can lead to high morbidity and mortality each year. Like other viruses, influenza virus can hijack host cellular machinery for its replication. Host cells have evolved diverse cellular defense to resist the invasion of viruses. As the main components of promyelocytic leukemia protein nuclear bodies (PML-NBs), PML can inhibit the replication of many medically important viruses including IAV. However, the mechanism of PML against IAV is unclear. In the present study, we found PML was induced in response to IAV infection and ectopic expression of PML could inhibit IAV replication, whereas knockdown of endogenous PML expression could enhance IAV replication. Further studies showed that PML increased the expression of FBXW7 by inhibiting its K48-linked ubiquitination and enhanced the interaction between FBXW7 and SHP2, which negatively regulated IAV replication during infection. Moreover, PML stabilized RIG-I to promote the production of type I IFN. Collectively, these data indicated that PML inhibited IAV replication by enhancing FBXW7 expression in the antiviral immunity against influenza virus and extended the mechanism of PML in antiviral immunity.


Assuntos
Vírus da Influenza A , Influenza Humana , Proteína 7 com Repetições F-Box-WD/genética , Humanos , Replicação Viral
7.
Bioorg Chem ; 111: 104866, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33866237

RESUMO

Thirty new pentacyclic triterpenoids, including five oleanane-type (1-5), twenty-three ursane-type (9-23, 26-33) and two taraxerane-type (24 and 25), along with fourteen known triterpenoids, were isolated from the stems and branches of Enkianthus chinensis. Their structures were elucidated by extensive spectroscopic analyses, X-ray crystallographic data and electronic circular dichroism (ECD) techniques. Sixteen compounds (1-5, 9-13, 20, 22, 32, 34-36) bearing a gem-hydroxymethyl group at C-4 represent rare examples of pentacyclic triterpenoids. In the in vitro biological activity evaluation, compounds 8, 9, 12-14, 17, 24, and 44 exhibited potent hepatoprotective effects at 10 µM. Moreover, compound 25 showed latent activity against HSV-1 with an IC50 value of 6.4 µM.


Assuntos
Antivirais/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Ericaceae/química , Herpesvirus Humano 1/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Antivirais/química , Antivirais/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Oxigênio/química , Caules de Planta/química , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação
8.
J Cell Mol Med ; 25(7): 3498-3510, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33682288

RESUMO

Transforming growth factor beta (TGF-ß) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation-associated responses. However, the antiviral activities and mechanisms of TGF-ß isoforms, including TGF-ß1, TGF-ß2 and TGF-ß3, remain unclear. Here, we demonstrated that all of the three TGF-ß isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-ß isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-ß isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-ß/SMAD signalling pathway-dependent and TGF-ß/SMAD signalling pathway-independent manners. TGF-ß isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-ß1 and TGF-ß2, not TGF-ß3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and α-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-ß isoforms in the HCV-related liver disease progression.


Assuntos
Hepacivirus/efeitos dos fármacos , Hepacivirus/crescimento & desenvolvimento , Hepatite C/virologia , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Sequência de Aminoácidos , Antivirais/farmacologia , Linhagem Celular Tumoral , Hepatite C/patologia , Humanos , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacologia , RNA Viral , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta2/metabolismo , Fator de Crescimento Transformador beta2/farmacologia , Fator de Crescimento Transformador beta3/metabolismo , Fator de Crescimento Transformador beta3/farmacologia , Internalização do Vírus/efeitos dos fármacos
9.
Bioorg Chem ; 110: 104734, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33689976

RESUMO

Seventeen new prenylated C6-C3 derivatives, namely, illifargeins A-M (1-13), including three pairs of enantiomers (1, 5, and 12) and one norillifargeal A (14), together with eight known analogues (15-22), were isolated from the stems and leaves of Illicium fargesii. The structures of the new compounds were elucidated using spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). Their absolute configurations were determined by using experimental and calculated ECD data analysis, as well as a modified Mosher's method. Compounds 1a, 1b, 2, 3, 5a, 7, 10, 11, 15, 16, 19, and 20 showed potential activity against Coxsackie virus B3, with IC50 values ranging from 6.23 to 33.33 µM. Compounds 9 and 15 exhibited potential activity against influenza virus A, with IC50 values of 11.11 and 19.24 µM, respectively. Compounds 2, 3, and 18 exhibited potential anti-oxidant activity, with IC50 values ranging from 1.43 to 6.71 µM.


Assuntos
Antivirais/farmacologia , Enterovirus/efeitos dos fármacos , Illicium/química , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Folhas de Planta/química , Caules de Planta/química , Antioxidantes , Antivirais/química , Desenho de Fármacos , Descoberta de Drogas , Estrutura Molecular
10.
J Org Chem ; 86(2): 2017-2022, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33397108

RESUMO

Illihenin A (1), a novel sesquiterpenoid, was isolated from the roots of Illicium henryi. The structure was determined by spectroscopic analyses, ECD calculation, and single-crystal X-ray diffraction. Compound 1 represents a class of novel 5/7/6 tricyclic sesquiterpenoids featuring a rare cage-like tricyclo[6.2.2.01,5]dodecane core. A plausible biosynthetic pathway of 1 by rearrangement of allo-cedrane is proposed. Additionally, 1 showed potent antiviral activity against coxsackievirus B3 with an IC50 value of 2.87 µM.


Assuntos
Illicium , Sesquiterpenos , Alcanos , Antivirais/farmacologia , Estrutura Molecular , Sesquiterpenos/farmacologia , Esqueleto
11.
Drug Des Devel Ther ; 14: 3723-3729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982177

RESUMO

INTRODUCTION: Hepatitis B virus (HBV) is a global health concern that can cause acute and chronic liver diseases. Thus, there is an urgent need to research novel anti-HBV agents. Our previous reports show that N-phenylbenzamide derivatives exert broad-spectrum antiviral effects against HIV-1, HCV, and EV71 by increasing intracellular levels of APOBEC3G (A3G). As A3G is capable of inhibiting the replication of HBV, we screened the N-phenylbenzamide derivatives against HBV. METHODS: In this study, a new derivative, N-(4-chlorophenyl)-4-methoxy-3-(methylamino) benzamide (IMB-0523), was synthesized and its anti-HBV activity was evaluated in vitro and in vivo. The acute toxicity and pharmacokinetic profiles of IMB-0523 were also investigated. RESULTS: Our results show that IMB-0523 has higher anti-HBV activity in both wild-type HBV (IC50: 1.99 µM) and drug-resistant HBV (IC50: 3.30 µM) than lamivudine (3TC, IC50: 7.37 µM in wild-type HBV, IC50: >440 µM in drug-resistant HBV). The antiviral effect of IMB-0523 against HBV may be due to an increased level of intracellular A3G. IMB-0523 also showed low acute toxicity (LD50: 448 mg/kg) in mice and promising PK properties (AUC0-t: 7535.10±2226.73 µg·h/L) in rats. Further, IMB-0523 showed potent anti-HBV activity in DHBV-infected ducks. CONCLUSION: Thus, IMB-0523 may be a potential anti-HBV agent with different mechanisms than current anti-HBV treatment options.


Assuntos
Antivirais/farmacologia , Benzamidas/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Administração Oral , Animais , Antivirais/síntese química , Antivirais/química , Benzamidas/síntese química , Benzamidas/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Patos , Feminino , Células Hep G2 , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Replicação Viral/efeitos dos fármacos
12.
Ying Yong Sheng Tai Xue Bao ; 31(7): 2399-2406, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32715706

RESUMO

The rapid monitoring of soil organic matter (SOM) content in large-scale salinized wheat fields can provide data for promoting research in saline soils and carbon cycle. Based on field sampling and remote sensing images of unmanned aerial vehicle, we established remote sensing prediction models of regional SOM using three methods, i.e., multiple linear regression (MLR), partial least squares (PLSR), and support vector machine regression (SVR) for bare land and wheat field, respectively. The models were validated and compared to identify the optimal inversion model of SOM. Moreover, the SOM in the area was inverted using the optimal model, with the inversion results being compared with the data by interpolation. The results showed that the spectrum after the filtering of 5×5 median was best related to surface SOM. Among the three models, the SVR model had the highest prediction accuracy, followed by the PLSR, while the MLR lowest. The SVR model was the best one for estimating wheat field, with coefficient of determination (R2) and root mean square error (RMSE) of 0.89 and 0.20, respectively, and the validated R2 and RMSE were 0.82 and 0.24, respectively. The bare land SOM was also best fitted by the SVR model, with R2 and RMSE were 0.63, 0.26, respectively, and the verified R2 and RMSE were 0.61, 0.25, respectively, but without statistical significance. The inversion of the optimal model revealed that SOM content in this region ranged from 17.51 to 22.53 g·kg-1, with an average of 19.51 g·kg-1, which was generally consistent with the field measurement. Compared with the inversion results, the interpolation data were limited in accuracy. Overall, our study suggested that the unmanned aerial vehicle-based multi-spectral analysis could be applied to quick and accurate estimation of SOM content in saline soil at the jointing stage of winter wheat.


Assuntos
Solo , Triticum , Análise dos Mínimos Quadrados , Tecnologia de Sensoriamento Remoto , Estações do Ano
13.
Bioorg Chem ; 95: 103490, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31855821

RESUMO

A series of novel berberine (BBR) analogues were prepared and tested for their antiviral potencies against six different genotype Coxsackievirus B (CVB1-6) strains, taking BBR core for structural modification. Structure-activity relationship (SAR) research revealed that introduction of a primary amine through a linker at position 3 might be beneficial for both antiviral activity and safety. Compound 14c displayed most promising inhibitory potency with IC50 values of 3.08-9.94 µM against tested CVBs 2-6 strains and satisfactory SI value of 34.3 on CVB3, better than that of BBR. Also, 14c could inhibit CVB3 replication through down-regulating the expression of VP1 protein and VP1 RNA. The mechanism revealed that 14c could suppress host components JNK-MAPK, ERK-MAPK and p38-MAPK activation. Therefore, BBR derivatives were considered to be a new class of anti-CVB agents with an advantage of broad-spectrum anti-CVB potency.


Assuntos
Antivirais/farmacologia , Berberina/farmacologia , Enterovirus Humano B/efeitos dos fármacos , Antivirais/síntese química , Antivirais/química , Berberina/síntese química , Berberina/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
14.
J Asian Nat Prod Res ; 22(8): 762-773, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31321999

RESUMO

Coxsackievirus B3 (CVB3) infection causes many inflammation-related diseases, such as viral myocarditis and aseptic meningitis. However, no vaccines or drugs have been approved for prevention or therapy of CVB3-induced diseases. In this study, luteolin (3,4,5,7-tetrahydroxyflavone) had been found that could dose-dependently reduce the production of viral progeny and synthesis of CVB3 RNA and protein. The luteolin-mediated inhibition of CVB3 was found to be mechanistically possible, at least in part, through depressing the phosphorylation of p38 MAPK and JNK MAPK, and inhibiting NF-κB nuclear translocation and subsequently attenuated the expression of inflammatory cytokines in CVB3-infected cells. Luteolin may be a potential agent or supplement against CVB3 infection by inhibiting inflammation.


Assuntos
Enterovirus Humano B , Luteolina , Animais , Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Replicação Viral
15.
J Asian Nat Prod Res ; 21(4): 299-307, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30909734

RESUMO

Six new glycosides (1-6), together with three known ones, were isolated from the twigs and leaves of Rhododendron latoucheae. Their structures were elucidated based on the spectroscopic data, including infrared spectrometry, mass spectrometry, and nuclear magnetic resonance experiments, along with Mosher's method. In addition, all compounds were tested their antiviral (herpes simplex virus-1 and influenza A/95-359) activities.


Assuntos
Glicosídeos/isolamento & purificação , Rhododendron/química , Antivirais/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Espectroscopia de Ressonância Magnética , Folhas de Planta/química
16.
J Asian Nat Prod Res ; 21(12): 1205-1214, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30417663

RESUMO

Influenza A virus (IAV) causes high morbidity and significant mortality worldwide. Given the limitations of existing vaccination and antiviral drugs, it is urgent to develop new anti-influenza drugs. Flavonoids are natural polyphenolic compounds with broad applications to treatments for influenza infection. In this study, we demonstrated that santin, a flavonoid compound, showed anti-influenza activity in MDCK and THP-1 cells. Mechanistic studies revealed that santin depressed the phosphorylation of p38 MAPK, JNK/SAPK, ERK, and NF-κB factor and subsequently attenuated the expression of inflammatory cytokines in IAV-infected cells. Thus, santin is a potential candidate for the future development of anti-IAV drugs.


Assuntos
Vírus da Influenza A , Influenza Humana , Animais , Cães , Flavonoides , Células Madin Darby de Rim Canino , Estrutura Molecular , NF-kappa B , Transdução de Sinais , Replicação Viral
17.
Virology ; 528: 80-88, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30580124

RESUMO

The innate immunity plays an essential role in defending infection of Influenza A virus (IAV). The regulatory effect of heme oxygenase-1 (HO-1), a cytoprotective enzyme, on innate immunity has been revealed. In this study, we aim to confirm the antiviral effect of CoPP (Cobaltic Protoporphyrin IX Chloride), a potent HO-1 inducer on IAV infection and elucidate the possible mechanism of HO-1-mediated host innate immune responses. Our results show that CoPP exhibits broad-spectrum antiviral activities against IAV. Furthermore, CoPP attenuates IAV replication through inducing type I IFNs response, not depending on HO-1 enzymatic activity. We also provide direct evidence that HO-1-mediated type I IFN response activation is largely due to its interaction with IRF3, which then promotes IRF3 phosphorylation and nuclear translocation. These results suggest that HO-1 agonist CoPP suppresses IAV replication through IRF3-mediated generation of IFN-α/ß. Thus, therapeutic induction of HO-1 might be a promising strategy to combat IAV epidemics.


Assuntos
Ativadores de Enzimas/farmacologia , Heme Oxigenase-1/imunologia , Vírus da Influenza A/efeitos dos fármacos , Fator Regulador 3 de Interferon/imunologia , Protoporfirinas/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Cães , Regulação da Expressão Gênica/imunologia , Heme Oxigenase-1/genética , Imunidade Inata , Interferon-alfa/imunologia , Interferon beta/imunologia , Células Madin Darby de Rim Canino , Camundongos , Células RAW 264.7
18.
J Asian Nat Prod Res ; 21(6): 559-572, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30585522

RESUMO

Three new megastigmane glucosides (1-3) and two new monoterpenes (4-5), together with 14 related known compounds (6-19) were isolated from the twigs and leaves of Lyonia ovalifolia. The structures of the new compounds were determined by extensive MS, NMR, CD experiments and chemical methods. Compounds 2, 6, and 18 displayed potent antiviral activity against Coxsackie B3, with IC50 values between 6.4 and 14.6 µM. Additionally, compounds 6, 10, and 11 exhibited noteworthy anti-inflammatory activities, with inhibition rates ranging from 54.55% to 83.33% under the concentration of 10-5 M.


Assuntos
Cicloexanonas/química , Cicloexanonas/farmacologia , Ericaceae/química , Glucosídeos/química , Glucosídeos/farmacologia , Norisoprenoides/química , Norisoprenoides/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Chlorocebus aethiops , Enterovirus/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Monoterpenos/química , Monoterpenos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Folhas de Planta , Células RAW 264.7 , Células Vero
19.
Zhongguo Gu Shang ; 31(12): 1129-1135, 2018 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-30583653

RESUMO

OBJECTIVE: To study and measure the anatomic structure of lumbar vertebral endplate structure in healthy adults by computed tomography(CT) technique in order to provide a useful guidance for the optimal design and clinical application of lumbar prostheses. METHODS: Sixty healthy adults (male and female equals) were recruited for full-waist CT scan after signing the informed consent form in the imaging department of the Second Affiliated Hospital of Xi'an Jiaotong University. The scanning data was imported into the computer aided software Mimics 16.0 for 3D reconstruction and measurement. The acquisition indexes included median sagittal diameter, maximum coronal diameter, concavity depth, median sagittal depression angle, coronal depression angle and so on. Finally, the collected data were statistically analyzed by the statistical software. RESULTS: The median sagittal diameter and the maximum coronal diameter of the upper and lower endplates were not only different between the different sexes(P<0.05), but also were increased with the increase of the lumbar spine sequence. The concavity depth of upper and lower endplates had no gender differences(P>0.05), but had a little change from L1 to L5, fluctuating from 1.5 to 2.0 mm and from 2.2 to 3.9 mm, respectively. In the same sequence, the concavity depth of lower endplate in males was greater than that of upper endplate, and the difference was statistically significant(P<0.05), but there was no significant difference in the concavity depth of upper and lower endplate in females(P>0.05). Sagittal concavity angle and coronal concavity angle of upper and lower endplates changed slightly with the increase of vertebral order, and there was no gender difference in sagittal and coronal concavity angle of most vertebral sequences (P>0.05). Statistics showed that the largest concavity near the caudal lumbar endplate was located on the dorsal side of the endplate plane. CONCLUSIONS: The anatomical structure of the lumbar endplate is very complicated. It is important to master the anatomical parameters of the endplate and make full use of CT before operation for the development and clinical application of the lumbar prosthesis.


Assuntos
Vértebras Lombares , Região Lombossacral , Feminino , Humanos , Masculino , Próteses e Implantes , Tomografia Computadorizada por Raios X
20.
Cell Stem Cell ; 23(5): 665-676.e4, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30318303

RESUMO

Unisexual reproduction is widespread among lower vertebrates, but not in mammals. Deletion of the H19 imprinted region in immature oocytes produced bimaternal mice with defective growth; however, bipaternal reproduction has not been previously achieved in mammals. We found that cultured parthenogenetic and androgenetic haploid embryonic stem cells (haESCs) display DNA hypomethylation resembling that of primordial germ cells. Through MII oocyte injection or sperm coinjection with hypomethylated haploid ESCs carrying specific imprinted region deletions, we obtained live bimaternal and bipaternal mice. Deletion of 3 imprinted regions in parthenogenetic haploid ESCs restored normal growth of fertile bimaternal mice, whereas deletion of 7 imprinted regions in androgenetic haploid ESCs enabled production of live bipaternal mice that died shortly after birth. Phenotypic analyses of organ and body size of these mice support the genetic conflict theory of genomic imprinting. Taken together, our results highlight the factors necessary for crossing same-sex reproduction barriers in mammals.


Assuntos
Metilação de DNA/genética , Haploidia , Células-Tronco Embrionárias Murinas/metabolismo , Animais , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Embrionárias Murinas/citologia , Fenótipo
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