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1.
Organogenesis ; : 1-13, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33464989

RESUMO

As a chaperone protein of progesterone receptor (PR), FK-506 Binding Protein 52 (FKBP52) can enhance the activity of PR, but the mechanism of FKBP52 affecting PR expression levels is difficult to clarify. Here, we report a novel in vitro model of ectopic endometrial stromal cells (ESCM) established through the primary culture method of endometrial stromal cells, which is used to study the details of relationship between FKBP52 abnormality and PR expression level in endometriosis (Ems). At the same time, the clinical study of the relationship between FKBP52 and PR expression levels in endometriosis patients was used to verify our conclusions. The results showed that the expression levels of PR-A mRNA and protein in endometriosis are positively correlated with FKBP52 and the abnormality of FKBP52 leads to the decrease of PR-B mRNA and protein expression. When FKBP52 was deleted or reduced, the expression levels of m RNA and protein of PR-A and PR-B have decreased leading to the proliferation of ectopic endometrium cells (ESC) and the occurrence of endometriosis, which is consistent with the expression levels of clinical endometriosis patients and fully confirms our conclusions and reliability of the model, and has great guiding significance for the research of Ems disease occurrence mechanism and clinical treatment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33290085

RESUMO

Females and males of dioecious plants have evolved sex-specific characteristics in terms of their morphological and physiological properties. However, the differentiation of phyllosphere microbiota in dioecious plants remains largely unexplored. Here, the diversity and composition of female and male Populus cathayana phyllosphere bacterial and fungal communities were investigated using 16S rRNA/ITS1 gene-based MiSeq sequencing. The divergences of bacterial and fungal community compositions occurred between females and males. Both females and males had their unique phyllosphere bacteria and fungi microbiota, such as bacteria Gemmata (5.41%) and fungi Pringsheimia (0.03%) in females, and bacteria Chitinophaga (0.009%) and fungi Phaeococcomyces (0.02%) in males. Significant differences in the relative abundance of bacterial phyla Proteobacteria, Planctomycetes and the fungal phyla Ascomycota, Basidiomycota (P < 0.05) were also found between females and males. Some bacterial genera Spirosoma and Amnibacterium, and fungal genera Venturia, Suillus, and Elmerina were significantly enriched in males (P < 0.05). In contrast, fungal genera Phoma and Aureobasidium were found significantly higher in females than in males (P < 0.05). The mineral, inorganic and organic nutrients content contributed differently to the divergence of female and male phyllosphere microbial communities, with 87.08% and 45.17% of the variations being explained for bacterial and fungal communities, respectively. These results highlight the sexual discrimination of phyllosphere microbes on the dioecious plants and provide hints on the potential host-associated species in phyllosphere environments.

3.
Front Microbiol ; 11: 594065, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240248

RESUMO

The high incidence of bacterial vaginosis recurrence is common after treatment with an antibiotic agent and suggests the need for new treatments to prevent this. We conducted a randomized trial to evaluate the ability of maltose gel to treat bacterial vaginosis. Eighteen female rhesus macaques were randomly assigned, in a 2:1 ratio, to receive maltose gel or placebo gel by syringe to the fornix of the vagina for five consecutive days. We used 16S rRNA sequencing data from 70 swab samples of vaginal secretions in two groups in total on days 0, 3, and 5 after medication initiation and days 3 and 5 after medication withdrawal for the study of microbiome composition. We found that, in the placebo control group, there was no significant change in the composition and abundance of vaginal microbiota during the follow-up period. In the maltose gel test group, the abundance of Lactobacillus in the vagina microbiota increased gradually with the prolongation of the treatment time on Days 3 and 5 (ANOVA p = 6.99e-5 < 0.01) but began to decrease after the withdrawal of maltose gel, which was different from that of the control group. Correspondingly, the diversity and abundance of BV-related bacteria, Fusobacterium, Parvimonas, Mobiluncus, Campylobacter, Prevotella, and Sneathia, decreased on Day 0 to Day 5 of medication and increased after drug withdrawal in the maltose gel test group. The study confirms that maltose gel can facilitate the proliferation of Lactobacillus and promote the transition of the vaginal microbiota from BV-related bacteria dominant to Lactobacillus dominant in the rhesus macaque.

4.
Emerg Microbes Infect ; 9(1): 1793-1803, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32686602

RESUMO

Lethal infection of wild birds with different subtypes of H5 viruses continuously occur. To investigate the genetic evolution and pathogenicity of H5 viruses in wild birds, we performed a detailed genetic and biologic analysis of 27 viruses, including H5N1, H5N2, H5N6, and H5N8 subtypes, that were responsible for avian influenza outbreaks in wild birds in China over the past decade. We found that these 27 viruses, bearing different clades/subclades of HA, were complicated reassortants and formed 12 different genotypes. Ten of the viruses tested were highly pathogenic in chickens, but showed distinct pathotypes in ducks and mice. Five of these 10 viruses, which were all from clade2.3.4.4, could bind human-type receptors. Our findings reveal the diversity of the genetic and biologic properties of H5 viruses circulating in wild birds and highlight the need to carefully monitor and evaluate the risks these viruses pose to animal and public health.

5.
Reprod Biol Endocrinol ; 18(1): 73, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669123

RESUMO

BACKGROUND: With the rapid development of whole embryo freezing technology, more and more frozen-thawed embryo transfer (FET) was used in assisted reproductive technology. However, the best FET program for elderly women has not been finalized. We intended to explore the reproductive outcomes of traditional hormone replacement treatment and a gonadotropin-releasing hormone agonist (GnRHa) combined with hormone replacement treatment in the frozen-thawed embryo transfer cycle of elderly patients. METHODS: In this retrospective analysis, we analyzed 1264 elderly patients (aged 38 years or older) who underwent FET at three reproductive centers between 2015 and 2017. According to the endometrial preparation protocol, we divided the patients into a GnRHa combined with hormone replacement treatment (GnRHa-HRT) group and traditional hormone replacement treatment (HRT) group. The clinical pregnancy, ongoing pregnancy, live birth, and abortion rates were compared between groups. RESULTS: One-way analysis of variance of the two groups revealed no significant difference in the clinical (33.58% vs. 37.15%) and ongoing pregnancy rates (19.40% vs. 25.10%) between the GnRHa-HRT and HRT groups. The live birth rate (17.54% vs. 24.10% p = 0.0229) of the GnRHa-HRT group was lower than that of the HRT group, whereas the abortion rate (45.56% vs. 32.97% p = 0.0252) was higher than that of the HRT group. However, multivariate analysis showed no significant difference in the live birth rate (p = 0.1333) or abortion rate (p = 0.1881) between the GnRHa-HRT and HRT groups. The number of embryos transferred, level of the embryo, and age and ovarian reserve of the patient significantly affected final reproductive outcomes. CONCLUSION: A GnRH agonist combined with hormone replacement therapy did not improve the reproductive outcomes of frozen-thawed embryo cycles in elderly patients.

6.
Anal Chem ; 92(14): 9454-9458, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32615038

RESUMO

The outbreak of SARS-CoV-2 is posing serious global public health problems. Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. The assay demonstrated high sensitivity and specificity, which is promising for the diagnosis and monitoring as well as control of SARS-CoV-2 worldwide.


Assuntos
Anticorpos Antivirais/análise , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Imunoensaio/métodos , Imunoglobulina G/análise , Imunoglobulina M/análise , Técnicas Analíticas Microfluídicas/métodos , Pneumonia Viral/diagnóstico , Técnicas de Laboratório Clínico/métodos , Ensaio de Imunoadsorção Enzimática , Humanos , Pandemias , Faringe/química , Faringe/imunologia , Sensibilidade e Especificidade
7.
Protein Cell ; 11(12): 894-914, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32562145

RESUMO

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.

8.
CNS Neurosci Ther ; 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32562344

RESUMO

BACKGROUNDS: Insults to the axons in the optic nerve head are the primary cause of loss of retinal ganglion cells (RGCs) in traumatic, ischemic nerve injury or degenerative ocular diseases. The central nervous system-specific leucine-rich repeat protein, LINGO-1, negatively regulates axon regeneration and neuronal survival after injury. However, the upstream molecular mechanisms that regulate LINGO-1 signaling and contribute to LINGO-1-mediated death of RGCs are unclear. METHODS: The expression of SP1 was profiled in optic nerve crush (ONC)-injured RGCs. LINGO-1 level was examined after SP1 overexpression by qRT-PCR. Luciferase assay was used to examine the binding of SP1 to the promoter regions of LINGO-1. Primary RGCs from rat retina were isolated by immunopanning and RGCs apoptosis were determined by Tunnel. SP1 and LINGO-1 expression was investigated using immunohistochemistry and Western bolting. Neuroprotection was assessed by RGC counts, RNFL thickness, and VEP tests after inhibition of SP1 shRNA. RESULTS: We demonstrate that SP1 was upregulated in ONC-injured RGCs. SP1 was bound to the LINGO-1 promoter, which led to increased expression of LINGO-1. Treatment with recombinant Nogo-66 or LINGO-1 promoted apoptosis of RGCs cultured under serum-deprivation conditions, while silencing of SP1 promoted the survival of RGCs. SP1 and LINGO-1 colocalized and were upregulated in ONC-injured retinas. Silencing of SP1 in vivo reduced LINGO-1 expression and protected the structure of RGCs from ONC-induced injury, but there was no sign of recovery in VEP. CONCLUSIONS: Our findings imply that SP1 regulates LINGO-1 expression in RGCs in the injured retina and provide insight into mechanisms underlying LINGO-1-mediated RGC death in optic nerve injury.

9.
Zhongguo Zhong Yao Za Zhi ; 45(4): 755-763, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237475

RESUMO

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets on the reproductive system of Ⅱ type collagen induced arthritis(CIA) male rats, and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group(Con), model group(CIA), Tripterygium Glycosides Tablets clinical equivalent dose groups of 1, 2, 4 times(9, 18, 36 mg·kg~(-1)), 10 rats in each group, and were given by gavage once a day for 42 days after the first immunization. The organ index of testis and epididymis were calculated on days 21 and 42. Histopathological and morphological changes of testis and epididymis were observed under optical microscope. Sperm count, sperm malformation rate and sperm kinetic parameters in epididymal tissues were observed by computer assisted sperm analysis(CASA). The concentration of testosterone(T), nitric oxide synthase(NOS) and aromatase(CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of testis and epididymis. The results showed that, compared with Con group, CIA group significantly increased the rate of testicular spermatogenic tubule lesion and sperm malformation, decreased the average path speed, and no significant changes were observed in other groups. Tripterygium Glycosides Tablets at 4 times clinical equivalent dose can significantly reduce the testis index(P<0.01), each dose group can reduce the epididymis index(P<0.05). Each dose group of Tripterygium Glycosides Tablets could cause different degrees of damage to the testis and epididymis, the proportion of testicular histopathology lesions increased, the number of spermatogenic cells in the seminiferous tubules decreased, and so on. It could reduce the number of sperm, increase the rate of sperm deformity, make the parameters of sperm dynamics abnormal, and so on. Tripterygium Glycosides Tablets at 4 times dose could significantly reduce the content of serum sex hormone T and key enzyme of androgen synthesis(P<0.05 or P<0.01), but had no effect on CYP19 A1. The expression of Bax and Bcl-2 in testis and epididymis were increased by 2 and 4 times doses of Tripterygium Glycosides Tablets(P<0.05, P<0.01 or P<0.01). The results showed that 21 d administration of Tripterygium Glycosides Tablets at equal or higher doses could induce obvious toxic effect to the reproductive organs of CIA male rats, and lower the level of serum sex hormone T and the key enzyme of androgen synthesis, NOS. The mechanism of abnormal changes of Bax and Bcl-2 in Testis and epididymis is still to be elucidated.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Genitália Masculina/efeitos dos fármacos , Glicosídeos/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Tripterygium/química , Animais , Artrite Experimental , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espermatozoides/patologia , Comprimidos , Testículo/patologia
10.
J Cancer ; 11(6): 1371-1382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32047544

RESUMO

Background: The latest WHO classification of CNS tumors using the integrated phenotypic and molecular parameters (IDH, ATRX, 1p19q, TERT etc.) have reestablished the CNS tumors classification in addition to traditional histology. The establishment of glioma molecular typing can more accurately predict prognosis, better guide individualized treatment to improve survival. Methods: The expression of IDH1, ATRX, PHH3, P53 and Ki67 was detected by IHC. Molecular status of IDH1/2 and TERT were analyzed using Sanger sequencing. MGMT was explored using methylation-specific PCR. 1p/19q codeletion status was firstly detected by FISH, then further confirmed by multiplex PCR-based next generation sequencing. Results: The mutation frequency of IDH1 was 68.7% (79/115) in WHO II astrocytoma, and 82 cases (82/344, 23.8%) were "triple-negative glioma" in our cohort. Multivariate COX analysis revealed that only IDH, 1p/19q, TERT and MGMT were independent prognostic factors. Noteworthily, we found 7 cases of the new molecular phenotype presented as "IDH wildtype and 1p/19q codeletion", not mentioned in the latest WHO guideline. Conclusion: We detected the newly recommended markers in a large cohort of Chinese glioma patients. Our data demonstrated a relatively lower frequency of IDH mutations and a higher prevalence of triple-negative glioma in Chinese compared with American and European, indicating ethnic and geographical difference in some markers. In addition, the new molecular phenotype "IDH wildtype and 1p/19q codeletion" glioma deserved special focus. These findings suggest that further stratification of infiltrating gliomas is needed for different treatment strategy and precision medicine.

12.
J Virol ; 94(2)2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694949

RESUMO

Influenza A virus (IAV) coopts numerous host factors to complete its replication cycle. Here, we identify free fatty acid receptor 2 (FFAR2) as a cofactor for IAV entry into host cells. We found that downregulation of FFAR2 or Ffar2 expression significantly reduced the replication of IAV in A549 or RAW 264.7 cells. The treatment of A549 cells with small interfering RNA (siRNA) targeting FFAR2 or the FFAR2 pathway agonists 2-(4-chlorophenyl)-3-methyl-N-(thiazol-2-yl)butanamide (4-CMTB) and compound 58 (Cmp58) [(S)-2-(4-chlorophenyl)-3,3-dimethyl-N-(5-phenylthiazol-2-yl)butanamide] dramatically inhibited the nuclear accumulation of viral nucleoprotein (NP) at early time points postinfection, indicating that FFAR2 functions in the early stage of the IAV replication cycle. FFAR2 downregulation had no effect on the expression of sialic acid (SA) receptors on the cell membrane, the attachment of IAV to the SA receptors, or the activity of the viral ribonucleoprotein (vRNP) complex. Rather, the amount of internalized IAVs was significantly reduced in FFAR2-knocked-down or 4-CMTB- or Cmp58-treated A549 cells. Further studies showed that FFAR2 associated with ß-arrestin1 and that ß-arrestin1 interacted with the ß2-subunit of the AP-2 complex (AP2B1), the essential adaptor of the clathrin-mediated endocytosis pathway. Notably, siRNA knockdown of either ß-arrestin1 or AP2B1 dramatically impaired IAV replication, and AP2B1 knockdown or treatment with Barbadin, an inhibitor targeting the ß-arrestin1/AP2B1 complex, remarkably decreased the amount of internalized IAVs. Moreover, we found that FFAR2 interacted with three G protein-coupled receptor (GPCR) kinases (i.e., GRK2, GRK5, and GRK6) whose downregulation inhibited IAV replication. Together, our findings demonstrate that the FFAR2 signaling cascade is important for the efficient endocytosis of IAV into host cells.IMPORTANCE To complete its replication cycle, IAV hijacks the host endocytosis machinery to invade cells. However, the underlying mechanisms of how IAV is internalized into host cells remain poorly understood, emphasizing the need to elucidate the role of host factors in IAV entry into cells. In this study, we identified FFAR2 as an important host factor for the efficient replication of both low-pathogenic and highly pathogenic IAV. We revealed that FFAR2 facilitates the internalization of IAV into target cells during the early stage of infection. Upon further characterization of the role of FFAR2-associated proteins in virus replication, we found that the FFAR2-ß-arrestin1-AP2B1 signaling cascade is important for the efficient endocytosis of IAV. Our findings thus further our understanding of the biological details of IAV entry into host cells and establish FFAR2 as a potential target for antiviral drug development.


Assuntos
Endocitose , Vírus da Influenza A/fisiologia , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais , Internalização do Vírus , Células A549 , Subunidades beta do Complexo de Proteínas Adaptadoras/genética , Subunidades beta do Complexo de Proteínas Adaptadoras/metabolismo , Animais , Cães , Células HEK293 , Humanos , Células Madin Darby de Rim Canino , Camundongos , Células RAW 264.7 , Receptores Acoplados a Proteínas-G/genética , Replicação Viral/fisiologia , beta-Arrestina 1/genética , beta-Arrestina 1/metabolismo
13.
J Virol ; 94(2)2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31666373

RESUMO

The low-pathogenic H7N9 influenza viruses that emerged in 2013 acquired an insertion of four amino acids in their hemagglutinin cleavage site and thereby became highly pathogenic to chickens in 2017. Previous studies indicated that these highly pathogenic H7N9 viruses are virulent in chickens but have distinct pathotypes in mice. A/chicken/Guangdong/SD098/2017 (CK/SD098) is avirulent, with a 50% mouse lethal dose (MLD50) of >7.5 log10 50% egg infectious dose (EID50), whereas A/chicken/Hunan/S1220/2017 (CK/S1220) is virulent in mice, with an MLD50 of 3.2 log10 EID50 In this study, we explored the genetic determinants that contribute to the difference in virulence between these two H7N9 viruses by generating a series of reassortants and mutants in the CK/S1220 virus background and testing their virulence in mice. We found that the reassortant CK/1220-SD098-NP, carrying the nucleoprotein (NP) of CK/SD098, was avirulent in mice, with an MLD50 of >107.5 EID50 The NPs of these two viruses differ by two amino acids, at positions 286 and 437. We further demonstrated that the amino acid mutations A286V and T437M of NP independently slowed the process of NP import to and export from the nucleus and thus jointly impaired the viral life cycle and attenuated the virulence of these H7N9 viruses in mice. Our study identified new virulence determinants in NP and provided novel targets for the development of live attenuated vaccines and antiviral drugs against influenza viruses.IMPORTANCE The H7N9 influenza viruses that emerged in China in 2013 have caused over 1,500 human infections, with a mortality rate of nearly 40%. The viruses were initially low pathogenic but became highly pathogenic in chickens at the beginning of 2017 and caused severe disease outbreaks in poultry. Several studies suggested that the highly pathogenic H7N9 viruses have increased virulence in mammals; however, the genetic basis of the virulence of H7N9 viruses in mammals is not fully understood. Here, we found that two amino acids, 286A and 437T, in NP are prerequisites for the virulence of H7N9 viruses in mice and the mutations A286V and T437M collectively eliminate the virulence of H7N9 viruses in mice. Our study further demonstrated that the virulence of influenza viruses is a polygenic trait, and the newly identified virulence-related residues in NP may provide new targets for attenuated influenza vaccine and antiviral drug development.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/metabolismo , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Mutação de Sentido Incorreto , Infecções por Orthomyxoviridae/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas do Core Viral/metabolismo , Substituição de Aminoácidos , Animais , Galinhas , Cães , Células HEK293 , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Vacinas contra Influenza/genética , Vacinas contra Influenza/metabolismo , Células Madin Darby de Rim Canino , Camundongos , Proteínas do Nucleocapsídeo , Infecções por Orthomyxoviridae/genética , Proteínas de Ligação a RNA/genética , Vacinas Atenuadas/genética , Vacinas Atenuadas/metabolismo , Proteínas do Core Viral/genética
14.
BioData Min ; 12: 21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807141

RESUMO

Background: The sequencing platform BGISEQ-500 is based on DNBSEQ technology and provides high throughput with low costs. This sequencer has been widely used in various areas of scientific and clinical research. A better understanding of the sequencing process and performance of this system is essential for stabilizing the sequencing process, accurately interpreting sequencing results and efficiently solving sequencing problems. To address these concerns, a comprehensive database, SEQdata-BEACON, was constructed to accumulate the run performance data in BGISEQ-500. Results: A total of 60 BGISEQ-500 instruments in the BGI-Wuhan lab were used to collect sequencing performance data. Lanes in paired-end 100 (PE100) sequencing using 10 bp barcode were chosen, and each lane was assigned a unique entry number as its identification number (ID). From November 2018 to April 2019, 2236 entries were recorded in the database containing 65 metrics about sample, yield, quality, machine state and supplies information. Using a correlation matrix, 52 numerical metrics were clustered into three groups signifying yield-quality, machine state and sequencing calibration. The distributions of the metrics also delivered information about patterns and rendered clues for further explanation or analysis of the sequencing process. Using the data of a total of 200 cycles, a linear regression model well simulated the final outputs. Moreover, the predicted final yield could be provided in the 15th cycle of the early stage of sequencing, and the corresponding R2 of the 200th and 15th cycle models were 0.97 and 0.81, respectively. The model was run with the test sets obtained from May 2019 to predict the yield, which resulted in an R2 of 0.96. These results indicate that our simulation model was reliable and effective. Conclusions: Data sources, statistical findings and application tools provide a constantly updated reference for BGISEQ-500 users to comprehensively understand DNBSEQ technology, solve sequencing problems and optimize run performance. These resources are available on our website http://seqBEACON.genomics.cn:443/home.html.

15.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3399-3405, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602901

RESUMO

Tripterygium wilfordii is widely used in the treatment of rheumatism with curative effect. However,its toxicity and adverse reactions,especially the hepatotoxicity,rank the first in the herbs induced liver injury,is the key factors hindering its clinical application. This paper reviewed the literatures related to the hepatotoxicity of T. wilfordii in recent 20 years,and summarized the characteristic of hepatotoxicity induced by T. wilfordii,the factors causing liver injury,the mechanism of toxicity,and the measures to reduce toxicity. In animal experiments,the T. wilfordii induced-hepatotoxicity in physiological state was more serious than pathological state. The T. wilfordii induced-hepatotoxicity is related to various toxic components contained in it,but alkaloids are the most toxic one.Overdose and cumulative overdose are the lead causing of hepatotoxicity induced by T. wilfordii. The theory of oxidative stress is still an important mechanism of T. wilfordii induced-hepatotoxicity,and Nrf2,as a key regulatory enzyme of oxidative stress,has become an important target for drugs to against T. wilfordii induced-hepatotoxicity. Mitochondrial autophagy and liver hypersensitivity are new mechanisms of liver injury induced by T. wilfordii. The measures such as dosage control,drug compatibility and dosage form variations can help to reduce the hepatotoxicity induced by T. wilfordii. This paper clarified the current situation and shortcomings of safety research on T. wilfordii,so as to propose new research strategies and provide ideas for rational evaluation of safety and clinical safe drug use of T. wilfordii.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Tripterygium/toxicidade , Animais
16.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3441-3447, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602907

RESUMO

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 µg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Tripterygium/química , Inibidores da Angiogênese/farmacologia , Angiotensina I/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Membrana Sinovial/efeitos dos fármacos , Comprimidos , Fator A de Crescimento do Endotélio Vascular
17.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3486-3493, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602913

RESUMO

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets( TG) on the reproductive system of Ⅱ type collagen induced arthritis( CIA) male rats,and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group( Con),model group( CIA),Tripterygium Glycosides Tablets clinical equivalent dose groups of 1,2,4 times( 9,18,36 mg·kg-1),10 rats in each group,and were given by gavage once a day for 42 days after the first immunization.The organ indexes of uterine and ovarian were calculated on days 21 and 42. Histopathological and morphological changes of uterine and ovarian were observed under optical microscope. The concentration of estradiol( E2),follicle-stimulating hormone( FSH),luteinizing hormone( LH),17α-hydroxylase( CYP17 A1) and cytochrome P450 19 A1( CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of uterus and ovary. The results showed that compared with the Con group,CIA group could reduce the number of uterine glands( P<0.05),but no significant changes were observed in other groups. Compared with the CIA group,there were no significant changes in the coefficients of uterus and ovary in the Tripterygium Glycosides Tablets groups. The number of uterine glands,total follicles in the ovary,mature follicles and corpus luteum,the distribution of blood vessels and mitochondria had a certain inhibitory trend,and also slightly increased the number of atresia follicles,but the histopathological quantitative indicators were not statistically different. Except that 2 times clinical dose of Tripterygium Glycosides Tablets could significantly reduce the content of CYP19 A1( P<0. 05) after 42 d administration,there were no significant changes in serum estrogen E2,FSH,LH and estrogen synthesis key enzymes CYP17 A1 in each administration group. Medium and high doses of Tripterygium Glycosides Tablets could increase the expression of apoptotic protein Bax in uterine and ovarian tissues( P<0. 05,P<0. 01),and all the administration groups could inhibit the expression of apoptotic inhibiting protein Bcl-2( P <0. 05,P<0. 01,P<0.001),42 d was more obvious than 21 d. In conclusion,4 times and less than 4 times Tripterygium Glycosides Tablets did not cause obvious toxicity and histopathological changes in the reproductive organs of CIA rats,but it could reduce the level of serum estrogen synthesis key enzyme CYP19 A1 and affect the content of apoptosis-related proteins Bax and Bcl-2 in uterus and ovary tissues. The relevant mechanism needs further study.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/toxicidade , Genitália Feminina/efeitos dos fármacos , Glicosídeos/toxicidade , Tripterygium/química , Animais , Apoptose , Aromatase/metabolismo , Artrite Experimental/induzido quimicamente , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Glicosídeos/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Comprimidos
18.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3502-3511, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602915

RESUMO

The aim of this paper was to compare the properties of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets from dose-effect-toxicity on type Ⅱ collagen-induced arthritis( CIA) in rats. SD rats were randomly divided into eight groups,including normal group,model group,Tripterygium Glycosides Tablets groups( 1 times equivalent dose 0.009 g·kg-1,4 times equivalent dose 0.036 g·kg-1,16 times equivalent dose 0.144 g·kg-1),Tripterygium wilfordii Tablets groups( 1 times equivalent dose 0.007 5 mg·kg-1,4 times equivalent dose 0.030 mg·kg-1,16 times equivalent dose 0.120 mg·kg-1). Beginning on the first immunization,Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets administered intraperitoneally once a day. After the second immunization,the symptoms such as redness and swelling of joints were observed,and the clinical score and incidence of arthritis were evaluated. HE and Masson staining were used to examine the histopathological changes of joints. The expression level of anti-type Ⅱ collagen antibody Ig G in serum was detected by ELISA,routine testing of blood components,the concentration of ALP( alkaline phosphatase),ALT( alanine aminotransferase),AST( aspartate aminotransferase),GGT( gamma-glutamyltransferase),TBi L( total bilirubin),CRE( creatinine) and UREA( urea) in serum were detected by enzymatic assay. The rate of sperm deformity in the epididymis was evaluated under light microscope. The extent of damage to the testis and ovarian tissue was assessed by HE staining. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets attenuated the inflammation,redness,swelling and deformity of joints and reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile,it also exhibited obvious reduction in all pathological features such as joint synovitis,pannus,cartilage erosion and bone destruction. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets reduced Ig G in a dose-dependent manner,and Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets( P<0.05 or P<0.01). The high doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase the organ coefficient of liver and spleen and reduced RBC and HGB in CIA rats( P<0.01),and severity leading to death. Gastric mucosal injury and morphological changes of liver and kidney were not observed in CIA rats of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets treatment group. The 4 and 16 times doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase serum ALT,GGT and decrease CRE( P<0.05 or P<0.01). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could increase the sperm deformity rate and damage the testicular seminiferous tubules of CIA male rats. Severity increased with dose and time increasing. The effect of Tripterygium Glycosides Tablets( 16 times) is more significant than Tripterygium wilfordii Tablets( 16 times). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets significantly delayed onset of arthritis and inhibited the paw edema and arthritic score. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets also caused male reproductive damage,high dose affected hematopoiesis,and maximum dose leading to death. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets all depended on dose-effect-toxicity manner. Anti-arthritis effect of Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets,but the toxicity of Tripterygium Glycosides Tablets maximum dose is more obvious. The relevant conclusions of our study will provide experimental references for clinical rational use of drugs,and further clinical studies are needed to confirm our conclusions.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/toxicidade , Glicosídeos/administração & dosagem , Glicosídeos/toxicidade , Tripterygium/toxicidade , Animais , Relação Dose-Resposta a Droga , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Comprimidos
19.
Vaccine ; 37(40): 5925-5929, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31471151

RESUMO

Ducks play a key role in the maintenance and spread of avian influenza viruses (AIVs) in nature, and control of AIVs in ducks has important implications for AIV eradication from poultry. We previously constructed a recombinant duck enteritis virus (DEV), rDEVus78HA, that expresses the HA gene of an H5N1 AIV and showed that rDEVus78HA immunization provides complete protection against both DEV and H5N1 AIV challenge in specific-pathogen-free ducks. In this study, we performed a 60-week clinical trial and found that this rDEVus78HA vaccine can function as a bivalent vaccine in farmed ducks against lethal challenge with DEV and H5N1 virus. Moreover, we found that rDEVus78HA-vaccinated ducks were efficiently protected against challenges with recently isolated heterologous H5N6 and H5N8 viruses. Our results demonstrate that rDEVus78HA could be extremely valuable for the control of DEV and H5 AIVs in ducks.


Assuntos
Patos/imunologia , Enterite/imunologia , Vetores Genéticos/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Influenza Aviária/imunologia , Doenças das Aves Domésticas/imunologia , Animais , Patos/virologia , Enterite/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Vacinação/métodos , Vacinas Sintéticas/imunologia
20.
Emerg Microbes Infect ; 8(1): 1280-1290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31495283

RESUMO

The H3N2 influenza viruses became widespread in humans during the 1968 H3N2 pandemic and have been a major cause of influenza epidemics ever since. Different lineages of H3N2 influenza viruses are also commonly found in animals. If a different lineage of H3N2 virus jumps to humans, a human influenza pandemic could occur with devastating consequences. Here, we studied the genetics, receptor-binding properties, and replication and transmission in mammals of 15 H3N2 avian influenza viruses detected in live poultry markets in China. We found that the H3N2 avian influenza viruses are complicated reassortants with distinct replication phenotypes in mice. Five viruses replicated efficiently in mice and bound to both human-type and avian-type receptors. These viruses transmitted efficiently to direct-contact guinea pigs, and three of them also transmitted among guinea pigs and ferrets via respiratory droplets. Moreover, ferret antiserum induced by human H3N2 viruses did not react with any of the H3N2 avian influenza viruses. Our study demonstrates that the H3N2 avian influenza viruses pose a clear threat to human health and emphasizes the need for continued surveillance and evaluation of the H3N2 influenza viruses circulating in nature.


Assuntos
Transmissão de Doença Infecciosa , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/fisiologia , Influenza Aviária/virologia , Aves Domésticas/virologia , Ligação Viral , Animais , China , Modelos Animais de Doenças , Furões , Cobaias , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Camundongos Endogâmicos BALB C , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Vírus Reordenados/fisiologia , Receptores Virais/metabolismo , Doenças dos Roedores/virologia , Replicação Viral
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