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1.
Bioorg Chem ; 95: 103490, 2020 Jan.
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.

2.
J Asian Nat Prod Res ; : 1-12, 2019 Jul 19.
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.

3.
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
4.
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
5.
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 , 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
6.
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
7.
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
8.
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
9.
J Nat Prod ; 81(8): 1721-1733, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30106288

RESUMO

A hyphenated NMR technique (analytical HPLC with a DAD connected to MS, SPE, and NMR) has proven effective for the full structural analysis and identification of minor natural products in complex mixtures. Application of this hyphenated technique to the CH2Cl2-soluble fraction of Rhododendron latoucheae led to the identification of 15 new minor ursane-type 28-nortriterpenoids (1-15). Compounds 1 and 12 inhibited HSV-1 with IC50 values of 6.4 and 0.4 µM, respectively.


Assuntos
Componentes Aéreos da Planta/química , Folhas de Planta/química , Rhododendron/química , Triterpenos/química , Animais , Antivirais/química , Antivirais/farmacologia , Cromatografia Líquida de Alta Pressão , Cães , Herpesvirus Humano 1/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Células Madin Darby de Rim Canino , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Extratos Vegetais/química , Extração em Fase Sólida , Triterpenos/farmacologia , Células Vero
10.
Molecules ; 23(8)2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127288

RESUMO

Taking berberine (BBR) as the lead, 23 new BBR derivatives were synthesized and examined for their antiviral activities against four different genotype enterovirus 71 (EV71) strains with a cytopathic effect (CPE) assay. Structure-activity relationship (SAR) studies indicated that introduction of a suitable substituent at the 9-position might be beneficial for potency. Among them, compound 2d exhibited most potent activities with IC50 values of 7.12⁻14.8 µM, similar to that of BBR. The effect of 2d was further confirmed in a dose-dependent manner both in RNA and protein level. The mechanism revealed that 2d could inhibit the activation of MEK/ERK signaling pathway. Meanwhile, it could suppress the EV71-induced autophagy by activating AKT and inhibiting the phosphorylation of JNK and PI3KIII proteins. We consider BBR derivatives to be a new family of anti-EV71 agents through targeting host components, with an advantage of broad-spectrum anti-EV71 potency.


Assuntos
Antivirais/farmacologia , Autofagia/efeitos dos fármacos , Berberina/análogos & derivados , Berberina/farmacologia , Enterovirus Humano A/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Antivirais/síntese química , Berberina/síntese química , Humanos , MAP Quinase Quinase 4/antagonistas & inibidores , Fosforilação , Inibidores de Proteínas Quinases/síntese química , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
11.
Zhongguo Gu Shang ; 31(6): 543-549, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29945411

RESUMO

OBJECTIVE: To study the anatomical measurement of goat lumbar vertebrae and to compare with human lumbar vertebrae, so as to build the foundation for establishing animal models of lumbar prosthesis. METHODS: The anatomical parameters of the vertebral body, pedicle and intervertebral disc in the fresh lumbar vertebrae of Boer goat and the lumbar vertebrae of healthy adults were collected by computer aided software Mimics16.0, and the anatomical characteristics of the two lumbar vertebrae were compared with the statistical software. RESULTS: The anterior vertebral body height(VBHa) of goat lumbar was less than the middle vertebral body height(VBHm), which was less than the posterior vertebral body height(VBHp), and the maximum values were (38.7±2.9), (40.1±2.6) and (40.7±2.7) mm respectively. Its endplate width was greater than its depth, with the whole shaped like a heart or a kidney. The cranial endplate of goats was convex while the caudal endplate was depressed and the depression was small, with a maximum value of (1.6±0.6) mm. The pedicle height of goats increased from L11 to L̀ with the maximum of (30.5±1.9) mm; its pedicle width and angle increased firstly and then decreased with the increase of vertebra level and the minimum values were (6.7±0.4) mm and(45.9±2.6)° respectively. The anterior intervertebral disc height was larger than the middle which was larger than the posterior and all varied slightly with the changes of intervertebral spaces; the height and width of intervertebral foramen separately waved at (12.9±0.3) to (14.3±1.0) mm and (5.7±1.0) to (6.7±0.9) mm. The comparative results showed that the vertebral body height, pedicle height and angle of goats were greater than those of humans (P<0.05) while the width and depth of the endplate, the intervertebral disc height, and etc. were significantly smaller than those of humans (P<0.05). In addition, some structures, such as the height of pedicle and intervertebral disc, also showed different changing laws with the increase of vertebra level. CONCLUSIONS: Although there are similarities in goat lumbar spine in some aspects, such as endplate and foramen foramen, there are still many differences in many aspects. Understanding the anatomical characteristics of goat lumbar vertebrae and the difference between goat and human is of great guiding significance for the research of goat prosthesis and related technology.


Assuntos
Disco Intervertebral , Vértebras Lombares , Animais , Cabras , Crânio , Tomografia Computadorizada por Raios X
12.
Biomed Pharmacother ; 99: 848-858, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29710484

RESUMO

Circular RNAs (circRNAs) are non-coding RNAs that play key roles in the pathogenesis of diseases and are associated with human hepatocellular carcinoma (HCC). Previous reports have shown the circRNA hsa_circ_0005075 is highly expressed in HCC tissues, but its function is unknown. In this study, we confirmed circ_0005075 is significantly increased in HCC tissues and cell lines. This overexpression was associated with increased numbers of proliferative, migrated and invasive SMMC-7721 cells. In addition, hsa_circ_0005075 inhibited the transcription activity of miR-431 measured by dual-luciferase reporter assays. In contrast, silencing hsa_circ_0005075 decreased cell number. Finally, effects after hsa_circ_0005075 silencing were rescued by co-transfection with miR-431 inhibitor. These results suggest hsa_circ_0005075 promotes HCC via miR-431 regulation.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA/genética , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética
13.
Gene ; 668: 48-53, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-29775756

RESUMO

Aberrated glucose metabolism is a key future of cancer cells. Unlike normal cells, tumor cells favor glycolysis even in the presence of sufficient oxygen. Pyruvate kinase (PK), a key glucose metabolic enzyme, converts phosphoenolpyruvate (PEP) to pyruvate by transferring the high-energy phosphate group to adenosine diphosphate (ADP) to produce adenosine triphosphate (ATP). Pyruvate kinase M2 (PKM2), one of the four isozyme of PK, which universally expressed in rapidly proliferating cells such as embryonic cells and cancer cells. Recent years, more and more research suggested PKM2 plays a crucial role in cancer progression through both metabolic and non-metabolic pathways. On the one hand, the middle product of glycolysis, such as amino acids, nucleotides, lipids is necessary to rapid growth of cancer cells. On the other hand, PKM2 supports tumor growth through regulating the expression of gene that involved in cell proliferation, migration and apoptosis. In this article, we review the recent advances to further understand the regulation and function of PKM2 in tumorigenesis. Given its multiple effects on cancer, PKM2 may be a potential target for cancer diagnosis and treatment.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias/enzimologia , Hormônios Tireóideos/metabolismo , Carcinogênese , Regulação da Expressão Gênica , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia
14.
Biomed Rep ; 8(6): 535-539, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29774144

RESUMO

The aim of the present study was to evaluate the effects of passage and cryopreservation of choroid plexus epithelial cells on their secretion of neurotrophic factors. Choroid plexus epithelial cells were cryopreserved and thawed following primary culture or passage cultured for up to two passages. The supernatant of primary, first/second passage and cryopreserved-thawed choroid plexus epithelial cells was collected when cells reached 80-90% confluence. ELISA was used to quantify brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) levels in the cell supernatant. First passage and cryopreserved-thawed cells secreted less BDNF and CNTF compared with primary cultured cells and increased levels of these two factors compared with second passage cells, and increased levels of GDNF and NGF compared with primary cultured and second passage cells (all P<0.05). Therefore, first passage culture decreased BDNF and CNTF secretion but increased NGF and GDNF compared with primary culture; second passage culture diminished neurotrophic factor secretion compared with first passage culture; and cryopreservation did not weaken the function of choroid plexus epithelial cells in secreting BDNF, GDNF, NGF and CNTF. The current study demonstrates that first passage and cryopreserved-thawed choroid plexus epithelial cells have an enhanced function to secrete neurotrophic factors including BDNF, GDNF, NGF and CNTF.

15.
Zhongguo Gu Shang ; 31(4): 379-385, 2018 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-29772867

RESUMO

OBJECTIVE: To study whether lithium agent produces neuroprotective effect by inhibiting the nerve cell apoptosis of rats after spinal cord injury. METHODS: Forty-two male SD rats weighing 200 to 250 g were randomly divided into 3 groups: blank control group(n=6) without surgery, normal saline(NS) group(n=18) with intraperitoneal injection of NS (40 mg/kg); and Lithium chloride (Licl) group (n=18) with intraperitoneal injection of Licl (40 mg/kg). After Allen method modeling, Licl group started intraperitoneal injection of Licl solution (40 mg·kg⁻¹·d⁻¹) within 15 min after operation to the second week. NS group, during the same interval, was injected with a same amount of NS. Postoperative 3, 7, 14 d, BBB scores in each group were measured;the expression of Bcl-2 and Bax protein were observed by immunohistochemisty staining;TUNEL staining was used to observe the nerve cell apoptosis. RESULTS: The BBB scores in blank control group were 21. Postoperative 7, 14 d, BBB scores of Licl group were higher than that of NS group(P<0.05). As for the Bcl-2 protein expression, black control group has a level of 0.081±0.003;7 d and 14 d postoperatively, the level in Licl group was 0.151±0.003, 0.163±0.003 and in NS group, 0.143±0.003, 0.154±0.002, respectively. Licl group showed significantly increased Bcl-2 protein expression(P<0.05). As for the Bax protein expression, black control group showed a level of 0.071±0.003; 7 d and 14 d postoperatively, the level in Licl group was 0.121±0.002, 0.106±0.002 and in NS group was 0.126±0.001, 0.120±0.002, respectively. The Bax protein expression is significantly inhibited in the Licl group(P<0.05). In nerve cell apoptosis by TUNEL staining, the positive cells were fewer in the black control group with apoptosis index (AI) of 1.98±0.19;while 7d and 14d postoperatively, the AI of Licl group was 13.12±0.69, 4.29±1.00 and of NS group, 18.26±0.87, 5.48±0.70, respectively. Licl group showed significant inhibition of the cell apoptosis(P<0.05). CONCLUSIONS: Licl can promote the Bcl-2 protein expression and inhibit the Bax proteins expression in nerve cells of rat after SCI, thereby playing a role in the inhibition of nerve cell apoptosis. This may be one of the mechanisms that Licl can promote the recovery of motor function of rats after SCI.


Assuntos
Apoptose , Lítio/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Masculino , Neurônios/citologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismo
16.
Phytomedicine ; 44: 187-203, 2018 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-29526584

RESUMO

BACKGROUND: Fuzi, which is the processed lateral roots of Aconitum carmichaeli Debx. (Ranunculaceae), is a traditional herbal medicine that is well known for its excellent pharmacological effects and acute toxicity. Aconitum alkaloids are responsible for its pharmacological activity and toxicity. Although a large number of studies on Fuzi have been reported, no comprehensive review on its pharmacokinetics has yet been published. PURPOSE: This paper seeks to present a comprehensive review regarding the phytochemistry, pharmacokinetic features and toxicity of Fuzi. The regulation of drug-metabolizing enzymes (DMEs) and efflux transporters (ETs) by Fuzi is also concluded. Additionally, the use of Fuzi as a personalized medicine based on the bioavailability barrier (BB), which mainly comprises DMEs and ETs, is discussed. METHODS: All available information on Fuzi was collected by searching for key words in PubMed, ScienceDirect, CNKI, Google Scholar, Baidu Scholar, and Web of Science. RESULTS: Aconitum alkaloids, which mainly include diester-diterpene alkaloids (DDAs), monoester-diterpene alkaloids (MDAs) and unesterified-diterpene alkaloids (UDAs), could be detected after Fuzi ingestion in vivo. The Aconitum alkaloids are rapidly absorbed in the intestine and extensively distributed in the body. DMEs, especially CYP3A4/5, are responsible for various types of metabolic reactions of the Aconitum alkaloids. ETs, including P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP), are involved in the efflux of the DDAs and MDAs. The kidney is the most important organ involved in the excretion of the Aconitum alkaloids. DDAs are the main toxic compounds present in Fuzi, and their acute toxicity is mainly due to their effects on the voltage-dependent sodium channels. Furthermore, Fuzi can substantially regulate DMEs and ETs. CONCLUSIONS: The toxicity of DDAs is acute. However, further investigations are necessary to determine the exact toxicological mechanisms. The significant impact of Fuzi on DMEs and ETs suggests that the co-administration of Fuzi with drugs that are substrates of DMEs and/or ETs may cause herb-drug interactions (HDIs). The BB network controlled exposure to the Aconitum alkaloids in vivo. Polymorphisms of DMEs and ETs in different individuals contribute to the differences in the efficacy and toxicity of Fuzi ingestion. In the future, the use of Fuzi as personalized medicine based on the BB network is necessary and practical to achieve ideal therapeutic efficacy with minimal toxicity.


Assuntos
Diterpenos/química , Diterpenos/farmacocinética , Aconitum/química , Alcaloides/química , Alcaloides/farmacocinética , Alcaloides/farmacologia , Animais , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Diterpenos/toxicidade , Interações Ervas-Drogas , Humanos , Inativação Metabólica/efeitos dos fármacos , Fitoterapia/métodos , Extratos Vegetais/química , Medicina de Precisão , Distribuição Tecidual
17.
Zhongguo Gu Shang ; 31(1): 12-17, 2018 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-29533031

RESUMO

OBJECTIVE: To study the change trend of cervical range of motion(ROM) after single-level anterior cervical corpectomy and fusion(ACCF) in treating cervical spondylotic myelopathy. METHODS: The clinical data of 23 patients with cervical spondylotic myelopathy was retrospectively analyzed from February 2015 to April 2016. There were 11 males and 12 females, with an average age of (54.6±13.3) years. All the patients were diagnosed as cervical spondylotic myelopathy by interrogation, physical examination and radiology, and were treated by ACCF. The Coda motion system was applied to assess the cervical range of motion pre-and post-operation. JOA and VAS scores were used to evaluate the clinical outcomes. RESULTS: The mean follow-up time was (9.4±1.6) months. Cervical ROM in all directions at 3 months postoperatively were significantly lower except for the left rotation(P<0.05). There was significant difference of cervical ROM in all directions between preoperative and 6 months postoperatively(P>0.05). The right lateral bending and the left rotation at 9 months postoperatively increased significantly(P<0.05). Postoperative extension at 6 months was significantly better than that of 3 months postoperatively(P<0.05). The extension, left and right lateral bending and left rotation at 9 months postoperatively were significantly better than of 6 months postoperatively(P<0.05). Postoperative JOA scores at each time points were significantly higher than that of preoperative(P<0.05) and VAS scores at each time points were significantly lower than that of preoperative(P<0.05). CONCLUSIONS: The change trend of three-dimensional cervical ROM after single-level ACCF revealed that the ROM decreased in short term, and later increased and was better than the preoperative level. Meanwhile, the neurological function improved significantly. But the short-term and long-term change trend of ROM postoperatively and the change trend of ROM after multi-level ACCF need to be further studied.


Assuntos
Vértebras Cervicais/cirurgia , Amplitude de Movimento Articular , Doenças da Medula Espinal/cirurgia , Fusão Vertebral , Espondilose/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Zhongguo Gu Shang ; 31(1): 47-55, 2018 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-29533037

RESUMO

OBJECTIVE: To systematically evaluate the clinical effect of high frequency repeated transcranial magnetic stimulation(HF rTMS)therapy on dyskinesia in patients with incomplete spinal cord injury. METHODS: Randomized controlled trials(RCTs) about HF rTMS therapy on patients with motor incomplete spinal cord injury were searched electronically in PubMed, Google scholar, Cochrane library, Clinical trial, Medline, Web of science, CNKI, VIP, and Wanfang database before October 2016. Two reviewers independently screened the literatures according to the inclusion and exclusion criteria, as well as extracted the data and assessed the methodological quality. The observed outcomes included ASIA motor score, ASIA lower extremities motor score(LEMS), Modified Ashworth score (MAS), Ten-meter walking test (10MWT) and Walking index for SCI II(WISCI II), and the outcomes were analyzed using RevMan5.2 software provided by the Cochrane information management system. RESULTS: Five RCTs involved 103 patients were included, and 61 patients(experimental group) accepted real rTMS and physical rehabilitation care for SCI, 51 patients(control group) accepted only physical rehabilitation care. There were significant differences in ASIA motor score, LEMS and 10MWT between two groups after HF rTMS therapy (statistics were Z=2.96, P=0.003; Z=3.04, P=0.002; Z=2.16, P=0.03; respectively). When stimulating the leg motor cortex, there was significant difference in MAS between two groups(Z=2.79, P=0.005), and when stimulating the vertex, there was no significant difference(Z=0.09, P=0.93). There was no significant difference in WISCI IIscore after HF rTMS therapy between two groups(Z=0.90, P=0.37). CONCLUSIONS: HF rTMS can raise motor score in patients with incomplete spinal cord injury, improve the spasticity of the lower extremities, and increase the motor ability.


Assuntos
Discinesias/reabilitação , Traumatismos da Medula Espinal/reabilitação , Estimulação Magnética Transcraniana , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Med Chem ; 14(8): 764-772, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29473520

RESUMO

BACKGROUND: Influenza is still a serious threat to human health with significant morbidity and mortality, so it is desirable to develop novel anti-flu drug agents with novel structures. OBJECTIVE: The main purpose of this research was to explore broad-spectrum anti-flu agents and provide antiviral stockpiles in response to potential future influenza pandemics. METHODS: Fifteen novel 12N-substituted tricyclic matrinic derivatives were synthesized and evaluated for their anti-influenza activities against H1N1 subtype taking 12N-p-cyanobenzenesulfonyl matrinane (1) as the lead. All prepared compounds were characterized by 1H NMR, 13C NMR and ESI-HRMS. The pharmacokinetics (PK) profile of the key compound was also examined in this study. RESULT: The structure-activity relationship study indicated that suitable benzyl groups on 12N atom might be beneficial for the activity. Among them, 12N-p-carboxybenzyl matrinic butane (17g) exhibited the most promising activity with an IC50 value of 16.2 µM and a selective index (SI) value of over 33.4. In addition, compound 17g displayed a good in vivo pharmacokinetic profile with an area under the curve (AUC0-∞) value of 9.89 µM·h. CONCLUSION: We consider tricyclic matrinic butane derivatives to be a new class of anti-influenza agents and this study provided useful information on further optimization.


Assuntos
Alcaloides/farmacologia , Antivirais/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Quinolizinas/farmacologia , Alcaloides/administração & dosagem , Alcaloides/síntese química , Alcaloides/farmacocinética , Animais , Antivirais/administração & dosagem , Antivirais/síntese química , Antivirais/farmacocinética , Cães , Células Madin Darby de Rim Canino , Masculino , Quinolizinas/administração & dosagem , Quinolizinas/síntese química , Quinolizinas/farmacocinética , Ratos Sprague-Dawley , Relação Estrutura-Atividade
20.
J Org Chem ; 83(1): 167-173, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29188714

RESUMO

Secoheliosphanes A (1) and B (2) and secoheliospholane A (3), possessing an unusual 7,8-seco-jatrophane skeleton and an unprecedented 9,10-seco-7,10-epoxyjatropholane skeleton, respectively, were isolated from the whole plants of Euphorbia helioscopia, along with two biogenetically precursors, a new jatrophane diterpene, 2-epi-euphornin I (4) and a known jatrophane diterpene, euphoscopin A (5). Structures of 1-4 including absolute configurations were elucidated on the basis of spectroscopic data, X-ray crystallography, and chemical conversion. Compounds 1 and 2 were prepared from 4 and 5, respectively, confirming their structural assignments. Notably, 1 and 2 presented the first examples of seco-jatrophane-type diterpenoids and 3 featured a novel 5/6/7/7-fused tetracyclic ring skeleton. Among them, compound 2 showed modest activity against HSV-1 with IC50 value of 6.41 µM.


Assuntos
Antivirais/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Herpesvirus Humano 1/efeitos dos fármacos , Antivirais/química , Antivirais/isolamento & purificação , Cristalografia por Raios X , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
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