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1.
J Enzyme Inhib Med Chem ; 39(1): 2296355, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38234133

RESUMO

Orthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,ß-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1ß, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.


Assuntos
Artrite Reumatoide , Diterpenos , Orthosiphon , Humanos , Orthosiphon/química , Orthosiphon/metabolismo , Abietanos , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa , Diterpenos/farmacologia , Diterpenos/química , NF-kappa B/metabolismo
2.
J Virol ; 96(12): e0220521, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35638850

RESUMO

The pathogenesis of white spot syndrome virus (WSSV) is largely unclear. In this study, we found that actin nucleation and clathrin-mediated endocytosis were recruited for internalization of WSSV into crayfish hematopoietic tissue (Hpt) cells. This internalization was followed by intracellular transport of the invading virions via endocytic vesicles and endosomes. After envelope fusion within endosomes, the penetrated nucleocapsids were transported along microtubules toward the periphery of the nuclear pores. Furthermore, the nuclear transporter CqImportin α1/ß1, via binding of ARM repeat domain within CqImportin α1 to the nuclear localization sequences (NLSs) of viral cargoes and binding of CqImportin ß1 to the nucleoporins CqNup35/62 with the action of CqRan for docking to nuclear pores, was hijacked for both targeting of the incoming nucleocapsids toward the nuclear pores and import of the expressed viral structural proteins containing NLS into the cell nucleus. Intriguingly, dysfunction of CqImportin α1/ß1 resulted in significant accumulation of incoming nucleocapsids on the periphery of the Hpt cell nucleus, leading to substantially decreased introduction of the viral genome into the nucleus and remarkably reduced nuclear import of expressed viral structural proteins with NLS; both of these effects were accompanied by significantly inhibited viral propagation. Accordingly, the survival rate of crayfish post-WSSV challenge was significantly increased after dysfunction of CqImportin α1/ß1, also showing significantly reduced viral propagation, and was induced either by gene silencing or by pharmacological blockade via dietary administration of ivermectin per os. Collectively, our findings improve our understanding of WSSV pathogenesis and support future antiviral designing against WSSV. IMPORTANCE As one of the largest animal DNA viruses, white spot syndrome virus (WSSV) has been causing severe economical loss in aquaculture due to the limited knowledge on WSSV pathogenesis for an antiviral strategy. We demonstrate that the actin cytoskeleton, endocytic vesicles, endosomes, and microtubules are hijacked for WSSV invasion; importantly, the nuclear transporter CqImportin α1/ß1 together with CqRan were recruited, via binding of CqImportin ß1 to the nucleoporins CqNup35/62, for both the nuclear pore targeting of the incoming nucleocapsids and the nuclear import of expressed viral structural proteins containing the nuclear localization sequences (NLSs). This is the first report that NLSs from both viral structure proteins and host factor are elaborately recruited together to facilitate WSSV infection. Our findings provide a novel explanation for WSSV pathogenesis involving systemic hijacking of host factors, which can be used for antiviral targeting against WSSV disease, such as the blockade of CqImportin α1/ß1 with ivermectin.


Assuntos
Transporte Ativo do Núcleo Celular , Citoesqueleto , Proteínas Estruturais Virais , Vírus da Síndrome da Mancha Branca 1 , Animais , Antivirais , Astacoidea/virologia , Citoesqueleto/virologia , Ivermectina , Microtúbulos , Complexo de Proteínas Formadoras de Poros Nucleares , Replicação Viral , Vírus da Síndrome da Mancha Branca 1/patogenicidade
3.
Molecules ; 28(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37764389

RESUMO

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1ß and IL-8 and increase the expression of anti-inflammatory cytokine IL-10.


Assuntos
Gentiana , Pneumonia , Humanos , Terpenos/farmacologia , Fator de Necrose Tumoral alfa , Glucosídeos/farmacologia , Células A549 , Citocinas , Extratos Vegetais/farmacologia
4.
BMC Plant Biol ; 22(1): 407, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35987603

RESUMO

BACKGROUND: The pollen ornate surface of flowering plants has long fascinated and puzzled evolutionary biologists for their variety. Each pollen grain is contained within a pollen wall consisting of intine and exine, over which the lipoid pollen coat lies. The cytology and molecular biology of the development of the intine and exine components of the pollen wall are relatively well characterised. However, little is known about the pollen coat, which confers species specificity. We demonstrate three types of pollen coat in Zingiberaceae, a mucilage-like pollen coat and a gum-like pollen coat, along with a pollen coat more typical of angiosperms. The morphological differences between the three types of pollen coat and the related molecular mechanisms of their formation were studied using an integrative approach of cytology, RNA-seq and positive selection analysis. RESULTS: Contrary to the 'typical' pollen coat, in ginger species with a mucilage-like (Caulokaempferia coenobialis, Cco) or gum-like (Hornstedtia hainanensis, Hhn) pollen coat, anther locular fluid was still present at the bicellular pollen (BCP) stage of development. Nevertheless, there were marked differences between these species: there were much lower levels of anther locular fluid in Hhn at the BCP stage and it contained less polysaccharide, but more lipid, than the locular fluid of Cco. The set of specific highly-expressed (SHE) genes in Cco was enriched in the 'polysaccharide metabolic process' annotation term, while 'fatty acid degradation' and 'metabolism of terpenoids and polyketides' were significantly enriched in SHE-Hhn. CONCLUSIONS: Our cytological and comparative transcriptome analysis showed that different types of pollen coat depend on the residual amount and composition of anther locular fluid at the BCP stage. The genes involved in 'polysaccharide metabolism' and 'transport' in the development of a mucilage-like pollen coat and in 'lipid metabolism' and 'transport' in the development of a gum-like pollen coat probably evolved under positive selection in both cases. We suggest that the shift from a typical pollen coat to a gum-like or mucilage-like pollen coat in flowering plants is an adaptation to habitats with high humidity and scarcity of pollinators.


Assuntos
Zingiberaceae , Aclimatação , Perfilação da Expressão Gênica , Lipídeos , Pólen , Zingiberaceae/genética
5.
Acta Pharmacol Sin ; 43(1): 10-14, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33731774

RESUMO

Metabolic-associated fatty liver disease (MAFLD) is the most common metabolic disease with a global prevalence of 25%. While MAFLD is serious and incurable at the later stage, it can be controlled or reversed at the early stage of hepatosteatosis originating from unhealthy diets. Recent laboratory evidence implicates a critical role of the mammalian target of rapamycin (mTOR)-autophagy signaling pathway in the pathogenesis of MAFLD induced by a high-fructose diet mimicking the overconsumption of sugar in humans. This review discusses the possible molecular mechanisms of mTOR-autophagy-endoplasmic reticulum (ER) stress in MAFLD. Based on careful analysis of recent studies, we suggest possible new therapeutic concepts or targets that can be explored for the discovery of new anti-MAFLD drugs.


Assuntos
Autofagia , Frutose/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Estresse do Retículo Endoplasmático , Frutose/efeitos adversos , Humanos , Transdução de Sinais
6.
J Enzyme Inhib Med Chem ; 37(1): 451-461, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35012401

RESUMO

Different oleanolic acid (OA) oxime ester derivatives (3a-3t) were designed and synthesised to develop inhibitors against α-glucosidase and α-amylase. All the synthesised OA derivatives were evaluated against α-glucosidase and α-amylase in vitro. Among them, compound 3a showed the highest α-glucosidase inhibition with an IC50 of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest α-amylase inhibitory with an IC50 of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds 3a and 3f were reversible and mixed types towards α-glucosidase and α-amylase, respectively. Molecular docking studies analysed the interaction between compound and two enzymes, respectively. Furthermore, cytotoxicity evaluation assay demonstrated a high level of safety profile of compounds 3a and 3f against 3T3-L1 and HepG2 cells.HighlightsOleanolic acid oxime ester derivatives (3a-3t) were synthesised and screened against α-glucosidase and α-amylase.Compound 3a showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound 3f presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and in silico studies analysed the binding between compounds and α-glucosidase or α-amylase.


Assuntos
Inibidores Enzimáticos/farmacologia , Ésteres/farmacologia , Ácido Oleanólico/farmacologia , Oximas/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Ésteres/síntese química , Ésteres/química , Humanos , Estrutura Molecular , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Oximas/síntese química , Oximas/química , Relação Estrutura-Atividade , alfa-Amilases/metabolismo
7.
Eur J Anaesthesiol ; 39(9): 758-765, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35919026

RESUMO

BACKGROUND: Identifying the interscalene brachial plexus can be challenging during ultrasound-guided interscalene block. OBJECTIVE: We hypothesised that an algorithm based on deep learning could locate the interscalene brachial plexus in ultrasound images better than a nonexpert anaesthesiologist, thus possessing the potential to aid anaesthesiologists. DESIGN: Observational study. SETTING: A tertiary hospital in Shanghai, China. PATIENTS: Patients undergoing elective surgery. INTERVENTIONS: Ultrasound images at the interscalene level were collected from patients. Two independent image datasets were prepared to train and evaluate the deep learning model. Three senior anaesthesiologists who were experts in regional anaesthesia annotated the images. A deep convolutional neural network was developed, trained and optimised to locate the interscalene brachial plexus in the ultrasound images. Expert annotations on the datasets were regarded as an accurate baseline (ground truth). The test dataset was also annotated by five nonexpert anaesthesiologists. MAIN OUTCOME MEASURES: The primary outcome of the research was the distance between the lateral midpoints of the nerve sheath contours of the model predictions and ground truth. RESULTS: The data set was obtained from 1126 patients. The training dataset comprised 11 392 images from 1076 patients. The test dataset constituted 100 images from 50 patients. In the test dataset, the median [IQR] distance between the lateral midpoints of the nerve sheath contours of the model predictions and ground truth was 0.8 [0.4 to 2.9] mm: this was significantly shorter than that between nonexpert predictions and ground truth (3.4 mm [2.1 to 4.5] mm; P < 0.001). CONCLUSION: The proposed model was able to locate the interscalene brachial plexus in ultrasound images more accurately than nonexperts. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov) identifier: NCT04183972.


Assuntos
Bloqueio do Plexo Braquial , Plexo Braquial , Anestésicos Locais , Inteligência Artificial , Plexo Braquial/diagnóstico por imagem , Bloqueio do Plexo Braquial/métodos , China , Humanos , Redes Neurais de Computação , Ultrassonografia de Intervenção/métodos
8.
J Virol ; 94(24)2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967962

RESUMO

As the most severely lethal viral pathogen for crustaceans in both brackish water and freshwater, white spot syndrome virus (WSSV) has a mechanism of infection that remains largely unknown, which profoundly limits the control of WSSV disease. By using a hematopoietic tissue (Hpt) stem cell culture from the red claw crayfish Cherax quadricarinatus suitable for WSSV propagation in vitro, the intracellular trafficking of live WSSV, in which the acidic-pH-dependent endosomal environment was a prerequisite for WSSV fusion, was determined for the first time via live-cell imaging. When the acidic pH within the endosome was alkalized by chemicals, the intracellular WSSV virions were detained in dysfunctional endosomes, resulting in appreciable blocking of the viral infection. Furthermore, disrupted valosin-containing protein (C. quadricarinatus VCP [CqVCP]) activity resulted in considerable aggregation of endocytic WSSV virions in the disordered endosomes, which subsequently recruited autophagosomes, likely by binding to CqGABARAP via CqVCP, to eliminate the aggregated virions within the dysfunctional endosomes. Importantly, both autophagic sorting and the degradation of intracellular WSSV virions were clearly enhanced in Hpt cells with increased autophagic activity, demonstrating that autophagy played a defensive role against WSSV infection. Intriguingly, most of the endocytic WSSV virions were directed to the endosomal delivery system facilitated by CqVCP activity so that they avoided autophagy degradation and successfully delivered the viral genome into Hpt cell nuclei, which was followed by the propagation of progeny virions. These findings will benefit anti-WSSV target design against the most severe viral disease currently affecting farmed crustaceans.IMPORTANCE White spot disease is currently the most devastating viral disease in farmed crustaceans, such as shrimp and crayfish, and has resulted in a severe ecological problem for both brackish water and freshwater aquaculture areas worldwide. Efficient antiviral control of WSSV disease is still lacking due to our limited knowledge of its pathogenesis. Importantly, research on the WSSV infection mechanism is also quite meaningful for the elucidation of viral pathogenesis and virus-host coevolution, as WSSV is one of the largest animal viruses, in terms of genome size, that infects only crustaceans. Here, we found that most of the endocytic WSSV virions were directed to the endosomal delivery system, strongly facilitated by CqVCP, so that they avoided autophagic degradation and successfully delivered the viral genome into the Hpt cell nucleus for propagation. Our data point to a virus-sorting model that might also explain the escape of other enveloped DNA viruses.


Assuntos
Astacoidea/metabolismo , Autofagia/fisiologia , Endossomos/metabolismo , Proteína com Valosina/metabolismo , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Astacoidea/virologia , Técnicas de Cultura de Células , Endossomos/virologia , Doenças dos Peixes/virologia , Concentração de Íons de Hidrogênio , Viroses
9.
Microb Pathog ; 150: 104681, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33296716

RESUMO

Bovine leukemia is a chronic, progressive, contagious tumor disease characterized by malignant lymphoid cell hyperplasia and systemic lymphadenopathy, and is caused by bovine leukemia virus (BLV). The disease affects almost all countries and regions where livestock are raised, and may even be a potential zoonotic disease. Monitoring and early prevention of bovine leukemia is very important. Therefore, we conducted this meta-analysis, the first of its type in the country, to estimate the prevalence of bovine leukemia in 1983-2019 in China. We included a total of 35 publications reported in 1983-2019 from the PubMed, ScienceDirect, Chinese Web of Knowledge (CNKI), VIP Chinese, and Wan Fang databases. In those articles, a total of 34,954 cattle had been tested, of which 4701 were positive for BLV infection. The estimated pooled BLV prevalence was 10.0% (4701/34,954). Subgroup analysis showed that there were significant differences for sampling years, detection methods, and age. BLV prevalence was highest in the following subgroups: sampled before 1985 (38.5%, 437/1134), age 3-5 years (22.5%, 231/1044), and detected by PCR (17.9%, 1228/5100). Regarding geographic factors, there were significant differences in the latitude and elevation subgroups. BLV prevalence was lowest in the subgroups of 20-30° latitude (3.3%, 255/5069) 200-1000 m altitude (2.2%, 560/11,990). We also analyzed other subgroups such as region, variety, breeding method, precipitation, humidity, and temperature, however, the differences were not significant. Our research indicated that the BLV was still prevalent in some of areas in China. We recommend strengthening the testing of cattle aged >1 year and using flexible testing methods such as PCR to control the prevalence of bovine leukemia and to prevent persistent infection.


Assuntos
Leucose Enzoótica Bovina , Vírus da Leucemia Bovina , Animais , Bovinos , China/epidemiologia , Leucose Enzoótica Bovina/epidemiologia , Vírus da Leucemia Bovina/genética , Reação em Cadeia da Polimerase , Prevalência
10.
Bioorg Chem ; 116: 105291, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34438122

RESUMO

In this study, twenty novel cinnamic acid magnolol derivatives were synthesized, and screened for their anti-hyperglycemic potential. All synthesized compounds exhibited good to moderate α-glucosidase and α-amylase inhibitory activities with IC50 values: 5.11 ± 1.46-90.26 ± 1.85 µM and 4.27 ± 1.51-49.28 ± 2.54 µM as compared to the standard acarbose (IC50: 255.44 ± 1.89 µM and 80.33 ± 2.95 µM, respectively). Compound 6j showed the strongest inhibitory activity against α-glucosidase (IC50 = 5.11 ± 1.46 µM) and α-amylase (IC50 = 4.27 ± 1.51 µM). Kinetic study indicated that compound 6j was reversible and a mixed type inhibitor against α-glucosidase and α-amylase. In silico studies revealed the binding interaction between 6j and two enzymes, respectively. Finally, cells cytotoxicity assay revealed that compound 6j showed low toxicity against 3 T3-L1 cells and HepG2 cells.


Assuntos
Compostos de Bifenilo/farmacologia , Cinamatos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Lignanas/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/química , Cinamatos/síntese química , Cinamatos/química , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Lignanas/síntese química , Lignanas/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Amilases/metabolismo
11.
Cutan Ocul Toxicol ; 40(1): 7-13, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33283549

RESUMO

Purpose: This study aimed to investigate the protective effects of quercetin on the tight junction proteins of human retinal pigment epithelial cells (ARPE-19 cells) suffering from oxidative stress injury and explore the possible mechanism.Methods: H2O2 (300 µM) was used to establish an oxidative stress model of ARPE-19 cells. ARPE-19 cells were pretreated with different concentrations (0-80 µM) of quercetin before H2O2 exposure. The expression and distribution of tight junction proteins and autophagy-related proteins were detected by Western blot and immunostaining. ARPE-19 cells were pretreated with 5 mM 3-methyladenine (3-MA).Results: The cell viability weakened in the H2O2 group compared with the control group. However, it was preserved after pretreatment with quercetin. It was observed that the expression levels of occludin, claudin-1 were decreased in the H2O2 group. Quercetin treatment significantly enhanced the expression levels of them as compared to the H2O2 group. H2O2 alone strongly decreased the Zonula occludens protein 1 (ZO-1) expression in the cytomembrane. Quercetin supplementation enhanced the accumulation of ZO-1 in ARPE-19 cells. The expression levels of Beclin-1 and Microtubule associated protein light chain 3 II (LC-3II) increased, and that of P62 decreased in the quercetin protection group. The appearance of LC-3II, which examined by immunofluorescence experiments, enhanced in the quercetin protection group as compared with the control group. The expression levels of beclin-1 and LC-3II increased, and that of P62 increased in the autophagy-inhibited group compared with the quercetin protection group. The levels of occludin and claudin-1 also decreased.Conclusion: Quercetin prevents the loss of tight junction proteins by upregulating autophagy after oxidative stress in ARPE-19 cells.


Assuntos
Autofagia/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Degeneração Macular/prevenção & controle , Substâncias Protetoras/farmacologia , Quercetina/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Humanos , Degeneração Macular/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Quercetina/uso terapêutico , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/patologia
12.
Microb Pathog ; 144: 104185, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32272215

RESUMO

BACKGROUND: Bovine viral diarrhea is an infectious disease that causes symptoms such as bovine diarrhea and abortion. It can cause severe losses to the animal husbandry, and the overall epidemic situation of yak's BVDV in China is unclear. Meta-analysis can reveal the basic epidemic situation of BVDV in different yak distribution areas in China, and estimate potentially related factors, to pave the way for clarifying the epidemic situation of yak in the domestic scope. METHODS: We proceeded to a systematic review and meta-analysis of data from papers on the BVDV incidence and prevalence in yaks in China by searching PubMed, ScienceDirect, Chinese Web of Knowledge (CNKI), Wanfang, and Chongqing VIP for publication from 1987 to 2019. We excluded reviews and duplicate studies, 24 studies denouncing the prevalence of BVDV in yak in China were selected upon our inclusion criterion finally. We estimated the pooled prevalence of BVDV infection in yaks by a random-effects model and evaluated its overall infection burden in China. FINDINGS: In total, the pooled prevalence of BVDV in yaks in China was 36.0% (95% CI 25.6%-46.4%) based on the data obtained from 13,446 yaks, by detecting antigens and antibodies. The highest BVDV positive rate in yak reached 67.5% in Xinjiang province of China. The prevalence in the six provinces of China was validated to be quite variable (24.4%-67.5%) and reached 369% in yaks of northwest China. Besides, the BVDV antigen-positive rate was estimated at 13.8% (95% CI 8.6%-19.0%) based on 5 studies, comparatively, the pooled BVDV antibody-based on 18 studies was about 32.9% (95% CI 24.6%-41.2%) in China. INTERPRETATION: This systematic review and meta-analysis firstly established an estimated prevalence of BVDV in yaks in China, as a whole, and estimates potential relevant factors, including geographic location, publication year, age, detection methods, etc., Our findings suggest that the scientific community or decision-makers can formulate corresponding prevention and control plans based on potential risk factors.


Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina/epidemiologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Vírus da Diarreia Viral Bovina , Animais , Bovinos , China/epidemiologia , Bases de Dados Factuais , Incidência , Prevalência
13.
Microb Pathog ; 139: 103908, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31830583

RESUMO

Mink Aleutian disease (AMD) is the first of the three major diseases of fur animals. It is a common immunosuppressive disease in mink farms worldwide, which seriously endangers the development of the mink farming industry. Strengthening the understanding of the positive serum rate and spatial distribution of AMD is of great significance for the prevention and control of disease caused by the Aleutian virus. Therefore, we conducted a systematic review and meta-analysis to assess the seroprevalence of AMD in China. We extracted 45 studies related to the seroprevalence of Chinese AMD, with samples taken between 1981 and 2017. Our systematic review and meta-analysis results show that, during the selected period, the overall positive rate of AMD in China was 55.3% (95% CI 48.5-62.0). The results from subgroups analysis of the potential risk factors showed that the seroprevalence rate of AMD in China in the past 36 years rose from 48% (95% CI 37.0-60.5) in 1981-2009 to 61.4% (95% CI 43.6-79.3) in 2010-2017. The date of the spatial difference in AMD seroprevalence indicated that AMD seroprevalence was unevenly distributed in different regions: the number of mink in eastern China and northeastern China was relatively high, and the seroprevalence rates were 57.9%, (95% CI 46.2-69.7) and 61.3% (95% CI 53.1-69.5), respectively. Central China had the highest seroprevalence rate of AMD at 69.8% (95% CI 64.4-75.2). At the provincial level, the AMD seroprevalence rate in Jiangsu was as high as 96% (95% CI 94.1-97.8), and the AMD seroprevalence rate in Shaanxi was the lowest at 22.1% (95% CI 20.3-23.9). This suggested that the AMD seroprevalence rate in China was unevenly distributed. In other subgroups, the positive rate of AMD in adult mink was higher than in juvenile mink. This implied that the high prevalence of AMD in China was caused by multiple factors. The meta-regression results indicated that the detection method subgroup (P = 0.008) may be the source of heterogeneity. Our data system evaluated the prevalence of Aleutian disease in China in the last 37 years and a preliminary discussion on the risk factors of AMD. It may help prevent and control AMD in China. It is recommended to conduct further epidemiological testing and develop a comprehensive testing plan to determine the risk factors associated with Aleutian disease and improve the Aleutian disease control strategy.


Assuntos
Vírus da Doença Aleutiana do Vison/isolamento & purificação , Doença Aleutiana do Vison/sangue , Doença Aleutiana do Vison/epidemiologia , Doença Aleutiana do Vison/virologia , Vírus da Doença Aleutiana do Vison/classificação , Vírus da Doença Aleutiana do Vison/genética , Vírus da Doença Aleutiana do Vison/imunologia , Animais , Anticorpos Antivirais/sangue , China/epidemiologia , Feminino , Masculino , Vison/imunologia , Vison/virologia , Filogenia , Prevalência , Estudos Soroepidemiológicos
14.
Microb Pathog ; 149: 104490, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32956791

RESUMO

Porcine circovirus type 2 (PCV2) causes infectious diseases in pigs leading to considerable economic losses in the pig industry. To prevent and control PCV2 infections, is important to understand the prevalence and geographical distribution of the virus. We performed the first systematic review and meta-analysis to estimate the prevalence of PCV2 in China. From PubMed, ScienceDirect, Chinese Web of Knowledge, Wanfang, and VIP Chinese Journal, we extracted 53 studies published in China between 2015 and 2019. There were 29,051 samples, 14,230 of which were positive for PCV2. The pooled prevalence of PCV2 was 46.0%, with the highest in Northeastern China (58.1%). The highest prevalence was 86.3% in Xinjiang province. Nursery pigs had the highest prevalence of PCV2 (50.9%), and the serological test detected the highest number of cases (58.5%). PCV2 prevalence was 50.1% in intensive farms and 37.5% in extensive farms. Our findings showed that PCV2 is common throughout China. Effective control measures are necessary to reduce PCV2 infections.


Assuntos
Infecções por Circoviridae , Circovirus , Doenças dos Suínos , Animais , China/epidemiologia , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/veterinária , Prevalência , Suínos , Doenças dos Suínos/epidemiologia
15.
Fish Shellfish Immunol ; 105: 244-252, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32693160

RESUMO

Barrier-to-autointegration factor (BAF) is a highly conserved DNA binding protein that participates in a variety of biological processes such as transcription, epigenetic regulation and antiviral immunity in vertebrates. However, the function of BAF is poorly understood in crustaceans. In this study, we identified a barrier-to-autointegration factor (CqBAF) from red claw crayfish Cherax quadricarinatus, which was responsive to white spot syndrome virus (WSSV) infection. The full-length cDNA sequence of CqBAF was 544 bp, including an open reading frame of 273 bp encoding 90 amino acids, a 107 bp of 5'-Untranslated Regions (5'-UTR) and a 164 bp of 3'-UTR. Gene expression analysis showed that CqBAF was distributed in all tissues examined with the highest expression in the crayfish haematopietic tissue (Hpt), which protein expression was also significantly up-regulated by WSSV infection in Hpt cells. Furthermore, the transcripts of both an immediate early gene IE1 and a late envelope protein gene VP28 of WSSV were clearly reduced in Hpt cells after gene silencing of CqBAF. Importantly, the promoter activity of two immediate early genes of WSSV, including WSV051 and IE1, was strongly enhanced by the increased phosphorylation of CqBAF, which also facilitated the accumulation of CqBAF protein in the cytoplasm of Sf9 cells. Taken together, these data suggest that CqBAF is likely to increase the replication of WSSV by promoting the transcription of viral immediate early genes, probably regulated by phosphorylation of CqBAF, which sheds new light on the molecular mechanism of WSSV infection.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Decápodes/genética , Decápodes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Vírus da Síndrome da Mancha Branca 1/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Astacoidea , Sequência de Bases , Proteínas de Ligação a DNA/química , Perfilação da Expressão Gênica , Filogenia , Alinhamento de Sequência
16.
Biol Pharm Bull ; 40(8): 1247-1254, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769006

RESUMO

Metformin is a commonly used drug for the treatment of type II diabetes and atorvastatin is the most prescribed cholesterol-lowering statin. The present study investigated the effects and mechanisms of metformin and atorvastatin in combination on human prostate cancer cells cultured in vitro and grown as xenograft tumor in vivo. Metformin in combination with atorvastatin had stronger effects on growth inhibition and apoptosis in PC-3 cells than either drug alone. The combination also potently inhibited cell migration and the formation of tumorspheres. Metformin and atorvastatin in combination had a potent inhibitory effect on nuclear factor-kappaB (NF-κB) activity and caused strong decreases in the expression of its downstream anti-apoptotic gene Survivin. Moreover, strong decreases in the levels of phospho-Akt and phosphor-extracellular signal-regulated kinase (Erk)1/2 were found in the cells treated with the combination. The in vivo study showed that treatment of severe combined immunodeficient (SCID) mice with metformin or atorvastatin alone resulted in moderate inhibition of tumor growth while the combination strongly inhibited the growth of the tumors. Results of the present study indicate the combination of metformin and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Atorvastatina/uso terapêutico , Metformina/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Atorvastatina/farmacologia , Linhagem Celular Tumoral , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Metformina/farmacologia , Camundongos SCID , NF-kappa B/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Survivina , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Phytochemistry ; 217: 113920, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37951561

RESUMO

Ten lignans, including six previously undescribed phenolic ester glycosyl lignans (1-6), were isolated from a well-known traditional Chinese medicine, Qin-Jiao, which is the dry root of Gentiana macrophylla Pall. (Gentianaceae). Their structures were determined by spectroscopic and chemical methods, especially 2D NMR techniques. Quantum chemical calculations of theoretical ECD spectra allowed the determination of their absolute configurations. Refer to its traditional applications for the treatment of rheumatic arthralgia and hepatopathy, these compounds were evaluated on a TNF-α induced MH7A human synoviocyte inflammation model and a D-GalN induced AML12 hepatocyte injury model. Compounds 1, 2, 5, and 6 significantly reduced the release of proinflammatory cytokine IL-1ß in MH7A cells at 15 µM and they also could strongly protect AML12 cells against D-GalN injury at 30 µM. Flow cytometry and Western blot analysis showed that compound 5 ameliorated D-GalN induced AML12 cell apoptosis by upregulating the expression of anti-apoptotic Bcl-2 protein and down-regulating the expression of pro-apoptotic Bax protein.


Assuntos
Medicamentos de Ervas Chinesas , Gentiana , Lignanas , Humanos , Gentiana/química , Lignanas/farmacologia , Glucosídeos/farmacologia , Glucosídeos/química , Medicamentos de Ervas Chinesas/farmacologia , Inflamação
18.
Toxicol Sci ; 191(2): 201-211, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36453845

RESUMO

Cadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illuminated. To understand what elements of BMPs and SMADs are affected by Cd to influence osteogenic differentiation and if BMPs can be the biomarkers of which Cd-induced osteoporosis, human bone marrow mesenchymal stem cells (hBMSCs) were treated with cadmium chloride (CdCl2) in vitro to detect the expression of BMPs and SMADs, and 134 subjects were enrolled to explore if the BMPs can be potential biomarkers of Cd-associated bone damage. Our results showed that Cd exposure significantly promoted the adipogenic differentiation of hBMSCs and inhibited its osteogenic differentiation by inhibiting the expression of BMP-2/4, SMAD4, and p-SMAD1/5/9 complex. And mediation analyses yielded that BMP-4 mediated 39.32% (95% confidence interval 7.47, 85.00) of the total association between the Cd and the risk of Cd-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared with CdCl2 only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage.


Assuntos
Cádmio , Osteogênese , Humanos , Proteína Morfogenética Óssea 4 , Cádmio/toxicidade , Cloreto de Cádmio/toxicidade , Diferenciação Celular , Biomarcadores
19.
Zhong Yao Cai ; 35(7): 1091-4, 2012 Jul.
Artigo em Zh | MEDLINE | ID: mdl-23252272

RESUMO

OBJECTIVE: To study the secondary metabolites of the marine fungus Penicillium sp. FS60 from the South China Sea and their cytotoxicities. METHODS: The compounds were isolated from the culture of strain FS60 by various chromatographic methods (silica gel, reverse silica gel, Sephadex-LH20, preparative TLC, HPLC and PTLC) and recrystallization. Their structures were identified by extensive analysis of their spectroscopic data. Compounds were tested for their cytotoxicities against SF-268, MCF-7, and NCI-H460 cell lines by SRB method. While, Compounds were tested for their antibacterial activities against S. aureus, E. coli and P. aeruginosa. RESULTS: Seven compounds were isolated from the culture and identified as methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate (1), 4-hydroxyacetophenone (2), 5-hydroxymethyl-furoic acid (3), isochromophilones VIII (4), ergosterol (5), ergosterol peroxide (6), and cerevisterol (7). CONCLUSION: Compound 1 is isolated from the genus Penicillium for the first time. Compound 3 is demonstrated to have significant inhibition against S. aureus and P. aeruginosa. Compound 4 is demonstrated to have significant inhibition against the three cell lines.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Furanos/isolamento & purificação , Penicillium/química , Acetofenonas/química , Acetofenonas/isolamento & purificação , Acetofenonas/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Benzopiranos/química , Benzopiranos/isolamento & purificação , Benzopiranos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , China , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/química , Furanos/farmacologia , Humanos , Estrutura Molecular , Oceanos e Mares , Penicillium/metabolismo
20.
Food Nutr Res ; 662022.
Artigo em Inglês | MEDLINE | ID: mdl-35757439

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disease that easily induces hepatitis, cirrhosis, and even liver cancer. The long-term use of NAFLD therapeutic drugs produces toxicity and drug resistance. Therefore, it is necessary to develop high efficiency and low-toxicity active ingredients to alleviate NAFLD. Objective: This study aimed to reveal the role and mechanism of a new functional food CMT in alleviating NAFLD. Results: In the ob/ob fatty liver mice models, the CMT extracts significantly inhibited the weight gain of the mice and reduced the accumulation of white fat. The anatomical and pathological results showed that CMT relieved fatty liver in mice and reduced excessive lipid deposition and inflammatory infiltration. Serological and liver biochemical indicators suggest that CMT reduced dyslipidemia and liver damage caused by fatty liver. CMT obviously activated the adenosine 5'-monophosphate-activated protein kinase (AMPK)/acetyl-coA carboxylase (ACC) and AMPK/fatty acid synthase (FAS) signaling pathways, promoted fat oxidation, and inhibited synthesis. Moreover, CMT regulated the expression of inflammatory factors to relieve hepatitis caused by NAFLD. Conclusion: The study explained the role and mechanism of CMT in alleviating NAFLD and suggested that the active ingredients of CMT might be beneficial in NAFLD therapy.

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