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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 194-201, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829691

RESUMO

Objective: To construct eukaryotic and prokaryotic recombinant vectors containing Pepck- Gp63 and to achieve protein expression by selecting the dominant epitope genes of Pepck and Gp63 of Leishmania infantum. Methods: The secondary structure and HLA epitopes of phosphoenolpyruvate carboxylase (PEPCK) were predicted by in silico analysis, and the dominant epitopes were picked out. According to the analysis results of glycoprotein of 63×10 3(GP63) epitopes identified by the same method in our laboratory, the dominant epitope genes of Pepck and Gp63 were used to construct pET32a- Pepck- Gp63 and pVAX1- Pepck- Gp63 by overlapping PCR and enzyme reaction. Then, for protein expression, the prokaryotic vectors were transfected into E.coil while the eukaryotic vectors were transfected into NIH3T3 cells by liposome transfection. Results: There were multiple dominant epitopes in Pepckand there were Pepck-Gp63 sequences in the polyclonal site of expression vector. The expression of Pepck-Gp63 in E.coil appeared in inclusion form and led to 74 kDa band in SDS-PAGE. The immunofluorescence results of NIH3T3 cells transfected by pVAX1- Pepck-Gp63 were positive. Conclusion: The recombinant prokaryotic expression plasmids pET32a- Pepck-Gp63 and eukaryotic expression plasmids pVAX1- P epck -Gp63 were successfully constructed, and it was shown that the recombinant plasmids were able to express the corresponding target proteins in E. coli and NIH3T3 cells, respectively, providing a preliminary experimental basis for the subsequent study of immunization strategies.


Assuntos
Leishmania infantum , Animais , Epitopos/genética , Escherichia coli/genética , Eucariotos , Vetores Genéticos/genética , Leishmania infantum/genética , Camundongos , Células NIH 3T3 , Fosfoenolpiruvato Carboxilase , Plasmídeos
2.
J Proteomics ; 239: 104184, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33711487

RESUMO

Persistent plant viruses multiply and circulate inside insect vectors following the route of midgut-hemolymph-salivary gland. Currently, how viruses interact with insect vectors after they are released into hemolymph is not entirely clear. In this study, we found that the hemolymph and fat body (HF) contained the highest Rice stripe virus (RSV) levels. Proteomic analysis on RSV-free and RSV-infected HF identified 156 differentially expressed proteins (DEPs), with the majority of them participating in metabolism, transportation, and detoxification. The RNA binding protein esf2 was the most downregulated protein. Knocking down the expression of esf2 did not influence the RSV burden, but caused the lethal effect to L. striatellus. In contrast, the mRNA decay protein ZFP36L1 was 69% more abundant upon RSV infection, and suppression of ZFP36L1 significantly increased the RSV burden. Our results reveal the potential role of ZFP36L1 in restricting the viral proliferation, and provide valuable clues for unravelling the interaction between RSV and L. striatellus in HF. SIGNIFICANCE: More than 76% of plant viruses are transmitted by insect vectors. For persistent propagative transmission, plant viruses multiply and circulate inside insects following the route of midgut-hemolymph-salivary gland. However, how viruses interact with vector insects after they are released into hemolymph is not entirely clear. Our study investigated the influence of rice stripe virus (RSV) on insect hemolymph and fat body by iTRAQ labeling method. Among the 156 differentially expressed proteins (DEPs) identified, two proteins associated with mRNA metabolism were selected for function analysis. We found that the mRNA decay activator protein ZFP36L1 influenced the RSV proliferation, and RNA binding protein esf2 caused the lethal effect to L. striatellus. Our results provide valuable clues for unveiling the interaction between RSV and L. striatellus, and might be useful in pest management.

3.
Virus Res ; 297: 198387, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33716181

RESUMO

White spot syndrome virus (WSSV), a double-stranded DNA virus that infects crustaceans, is the most serious viral pathogen affecting shrimp farming worldwide. To reduce the economic losses caused by WSSV, we screened a novel coumarin derivative from a small molecule drug library, N-(4-((4-(((2-oxo-2H-chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)sulfonyl)phenyl)acetamide (N2905), to evaluate its anti-WSSV effects in vivo. We determined that compound N2905, up to a concentration of 20 mg/L, significantly decreased the number of WSSV copies in Litopenaeus vannamei post-larvae, with a maximum inhibitory rate of > 90 %, and increased the survival rate of WSSV-infected post-larvae. Pre-treatment and post-treatment assays indicated that N2905 could treat, but not prevent, WSSV infections. When WSSV was preincubated with N2905 for 1-4 h, the incidence of viral infections was significantly reduced and survival time of post-larvae extended to 120 h. A stability study of N2905 provided a reference for its practical use. Considering the antiviral stability of N2905 in culture water within 2 d, continuous N2905 exchange was performed, showing a significant decrease in viral load at 120 h post-infection (hpi) and a 55 % increase in survival of WSSV-infected post-larvae. Overall, our study demonstrated the potential of N2905 as an antiviral agent.

4.
BMC Plant Biol ; 21(1): 51, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468046

RESUMO

BACKGROUND: Chinese wheat mosaic virus (CWMV) is a severe threat to winter wheat and is transmitted by Polymyxa graminis. The mechanisms of interactions between CWMV and plants are poorly understood. In this study, a comparative proteomics analysis based on nanoliquid chromatography mass spectrometry (MS)/MS was conducted to characterize proteomic changes in plants responding to CWMV infection. RESULTS: In total, 2751 host proteins were identified, 1496 of which were quantified and 146 up-regulated and 244 down-regulated proteins were identified as differentially expressed proteins (DEPs). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that DEPs were most strongly associated with photosynthesis antenna proteins, MAPK signaling plant and glyoxylate and dicarboxylate metabolism pathways. Subcellular localization analysis predicted that more than half of the DEPs were localized in the chloroplast, an organelle indispensable for abscisic acid (ABA) synthesis. Our results suggest that CWMV infection interrupts normal chloroplast functions and decreases ABA concentrations in Nicotiana benthamiana. Further analysis showed that the ABA pathway was suppressed during CWMV infection and that ABA treatment induced plant hosts defenses against CWMV. CONCLUSIONS: We identified several candidate proteins expressed during CWMV infection, and the ABA pathway was strongly associated with responses to CWMV infection in N. benthamiana.

5.
Org Lett ; 23(2): 571-577, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33373250

RESUMO

A highly enantioselective rhodium-catalyzed intermolecular hydroarylation of α-aminoalkyl acrylates using water as a direct proton source has been realized by employing a chiral bicyclo[3.3.0] diene ligand, allowing efficient access to a broad range of α-aryl-methyl-substituted ß2-, γ2-, and δ2-amino esters with excellent enantioselectivities (up to 98% ee) under exceptionally mild conditions. By utilizing this method, a series of structurally interesting benzo-fused heterocyclic molecules and the corresponding ß2-, γ2-, and δ2-amino acids are facilely constructed.

6.
Dev Comp Immunol ; : 103930, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33212093

RESUMO

Virus-encoded tumor necrosis factor receptors (vTNFRs) facilitate viral escape from the host immune response during viral propagation. Cyprinid Herpesvirus-2 (CyHV-2) is a double-stranded DNA virus of alloherpesviridae family that causes great economic losses in the aquaculture industry. The present study identified and characterized a novel TNFR homolog termed ORF4 in CyHV-2. ORF4 was identified as a secreted protein and a homolog of herpesvirus entry mediator (HVEM). ORF4 localized to the cytoplasm in infected GiCF cells. ORF4 overexpression enhanced viral propagation, while downregulation of ORF4 via siRNA decreased viral propagation. ORF4 overexpression promoted GiCF proliferation, and its downregulation suppressed CyHV-2-induced apoptosis. GST-pulldown and LC-MS/MS assays identified 44 conditional binding proteins that interact with ORF4 protein, while the GST pulldown test did not support the idea that ORF4 interact with histone H3.3. Taken together, our results contribute to our understanding of the vTNFR function in alloherpesviridae pathogenesis and host immune regulation.

7.
Ergonomics ; : 1-34, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026947

RESUMO

Seating is the overriding factor influencing aircraft cabin comfort. To efficiently enhance seat comfort, this paper proposes a method to identify key optimization points for seat comfort. Seat discomfort indicators are recognized based on a comparison of perceived performance with expectation. Confirmatory factor analysis is used to explore the latent variables of discomfort indicators, and a structural model was used to analyze correlations between latent variables. Finally, the most important latent variable influencing seat comfort was clarified. Analysis results of survey data from narrow-body aircraft show that seat discomfort indicators center on the physical performance of the seat and include four latent variables: support performance, personal space, contact surface features, and safety and stability. Support performance determines body posture while traveling and is the overriding latent variable influencing seat comfort. This research establishes aircraft seat discomfort indicators, latent variables formed through the mutual linkage of discomfort indicators, and the structural relations between latent variables. The results can assist in the formulation of comfort optimization procedures for aircraft seats.Practitioner Summary: A method identifying the key points of aircraft seat comfort optimization was proposed, which includes three steps: recognizing discomfort indicators, exploring the relationship between discomfort indicators, and confirming the most important variable influencing seat comfort. Results provide guidance for aircraft seat optimization.

8.
Environ Pollut ; 268(Pt B): 115860, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33120142

RESUMO

The methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is an important regulator for the balance of DNA methylation and hydroxymethylation through various pathways. Increasing evidence has suggested that TET1 probably involved in DNA methylation and demethylation dysregulation during chemical carcinogenesis. However, the role and mechanism of TET1 during lung cancer remains unclear. In this study, we found that TET1 expression was significantly down-regulated and the methylation level was significantly up-regulated in 3-methylcholanthrene (3-MCA) induced cell malignant transformation model, rat chemical carcinogenesis model, and human lung cancer tissues. Demethylation experiment further confirmed that DNA methylation negatively regulated TET1 gene expression. TET1 overexpression inhibited cell proliferation, migration and invasion in vitro and in vivo, while knockdown of TET1 resulted in an opposite phenotype. DNA hydroxymethylation level in the promoter region of base excision repair (BER) pathway key genes XRCC1, OGG1, APEX1 significantly decreased and the degree of methylation gradually increased in malignant transformed cells. After differential expression of TET1, the level of hydroxymethylation, methylation and expression of these genes also changed significantly. Furthermore, TET1 binds to XRCC1, OGG1, and APEX1 to maintain them hydroxymethylated. Blockade of BER pathway key gene alone or in combination significantly diminished the effect of TET1. Our study demonstrated for the first time that TET1 expression is regulated by DNA methylation and TET1-mediated hydroxymethylation regulates BER pathway to inhibit the proliferation, migration and invasion during 3-MCA-induced lung carcinogenesis. These results suggested that TET1 gene can be a potential biomarker and therapy target for lung cancer.

9.
Arch Virol ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33108486

RESUMO

The leaf beetle Aulacophora lewisii (family Chrysomelidae, order Coleoptera) is a common insect pest of cucurbitaceous vegetables. In this study, the complete genome sequence of a novel virus from a single leaf beetle was determined using metagenomic sequencing and rapid amplification of cDNA ends. A homology search and phylogenetic analysis suggested that the new virus belongs to the genus Iflavirus, family Iflaviridae, and it was tentatively named "Aulacophora lewisii iflavirus 1" (ALIV1). ALIV1 has a single positive-stranded RNA genome of 9655 nucleotides in length (excluding the polyA tail) that is predicted to encode typical conserved domains of iflaviruses, including two picornavirus-like capsid protein domains, a helicase domain, and an RNA-dependent RNA polymerase (RdRp) domain. Sequence comparisons showed that the full genome sequence of ALIV1 is most similar to that of Brevicoryne brassicae picorna-like virus, with 42.4% sequence identity, and it shares 60% sequence identity in the coat protein region with its closest homolog, Watson virus. The average coverage of the ALIV1 sequence was approximately 5000X, suggesting that it might actively replicate in the host. Phylogenetic analysis based on deduced amino acid sequences suggested that ALIV1 is closely related to Dinocampus coccinellae paralysis virus. To the best of our knowledge, ALIV1 is the first virus discovered in A. lewisii and is also the first iflavirus identified in a member of the genus Aulacophora.

10.
Insect Sci ; 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32757245

RESUMO

The whitefly Bemisia tabaci is a notorious agricultural pest of many crops worldwide. Although it is thought that B. tabaci secretes saliva into the host plant to counter plant defenses, knowledge on the whitefly salivary proteome is limited. Here, we characterized the gene/protein repertoires of B. tabaci salivary glands and secreted saliva by transcriptomic and liquid chromatography tandem mass spectroscopy analyses. A total of 698 salivary gland-enriched unigenes and 171 salivary proteins were identified. Comparative analysis between the B. tabaci salivary proteins and those of different arthropod species revealed numerous similarities in proteins associated with binding, hydrolysis, and oxidation-reduction, which demonstrates a degree of conservation across herbivorous saliva. There were 74 proteins only identified in B. tabaci saliva, of which 34 were B. tabaci-specific. In addition, 13 salivary proteins, of which 11 were B. tabaci-specific, were differentially regulated when B. tabaci fed on different hosts. Our results provide a good resource for future functional studies of whitefly salivary effectors, and might be useful in pest management.

11.
Viruses ; 12(7)2020 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-32604989

RESUMO

Negeviruses are a proposed group of insect-specific viruses that can be separated into two distinct phylogenetic clades, Nelorpivirus and Sandewavirus. Negeviruses are well-known for their wide geographic distribution and broad host range among hematophagous insects. In this study, the full genomes of two novel negeviruses from each of these clades were identified by RNA extraction and sequencing from a single dungfly (Scathophaga furcata) collected from the Arctic Yellow River Station, where these genomes are the first negeviruses from cold zone regions to be discovered. Nelorpivirus dungfly1 (NVD1) and Sandewavirus dungfly1 (SVD1) have the typical negevirus genome organization and there was a very high coverage of viral transcripts. Small interfering RNAs derived from both viruses were readily detected in S. furcata, clearly showing that negeviruses are targeted by the host antiviral RNA interference (RNAi) pathway. These results and subsequent in silico analysis (studies) of public database and published virome data showed that the hosts of nege-like viruses include insects belonging to many orders as well as various non-insects in addition to the hematophagous insects previously reported. Phylogenetic analysis reveals at least three further groups of negeviruses, as well as several poorly resolved solitary branches, filling in the gaps within the two sub-groups of negeviruses and plant-associated viruses in the Kitaviridae. The results of this study will contribute to a better understanding of the geographic distribution, host range, evolution and host antiviral immune responses of negeviruses.

12.
Molecules ; 25(12)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575562

RESUMO

Hyperactivation of microglia in the brain is closely related to neuroinflammation and leads to neuronal dysfunction. Costunolide (CTL) is a natural sesquiterpene lactone with wide pharmacological activities including anti-inflammation and antioxidation. In this study, we found that CTL significantly inhibited the production of inflammatory mediators including nitric oxide, IL-6, TNF-α, and PGE2 in lipopolysaccharide (LPS)-stimulated BV2 microglia. Moreover, CTL effectively attenuated IKKß/NF-κB signaling pathway activation. To identify direct cellular target of CTL, we performed high-throughput reverse virtual screening assay using scPDB protein structure library, and found cyclin-dependent kinase 2 (CDK2) was the most specific binding protein for CTL. We further confirmed the binding ability of CTL with CDK2 using cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assays. Surface plasmon resonance analysis also supported that CTL specifically bound to CDK2 with a dissociation constant at micromole level. Furthermore, knocking down CDK2 obviously reversed the anti-inflammation effect of CTL via AKT/IKKß/NF-κB signaling pathway on BV-2 cells. Collectively, these results indicate that CTL inhibits microglia-mediated neuroinflammation through directly targeting CDK2, and provide insights into the role of CDK2 as a promising anti-neuroinflammation therapeutic target.

13.
Pharmazie ; 75(5): 201-204, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32393429

RESUMO

Timosaponin B-II (TB-II; (25S)-26-(ß-D-glucopyranosyloxy)-3ß-[(2-O-ß-D-glucopyranosyl-ß-D-galactopyranosyl) oxy]-5ß-furostan-22-ol is extracted from Anemarrhena. Its anti-inflammation, anti-oxidation, and anti-asthma properties have been widely explored. However, its effect on the heart has not been reported. In this study, we used zebrafish as a research model to determine the effects of TB-II on the heart and its toxic and anti-inflammatory effects. To explore the cause of cardioprotective effects of TB-II, we used transgenic zebrafish with macrophages and neutrophils labeled with fluorescent protein. We found for the first time that TB-II had a protective effect on the zebrafish heart. It did not affect the survival and hatching rates of zebrafish embryos, indicating its low toxicity. Results showed that TB-II may have cardioprotective effects, which might be related to its anti-inflammatory effects.

14.
Org Biomol Chem ; 18(24): 4569-4574, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32253413

RESUMO

A highly enantiocontrolled room temperature rhodium-catalyzed conjugate arylation process was developed. The reaction proceeds through 1,4-addition of α-substituted acrylates followed by enantioselective protonation using a C1-symmetric chiral bicyclo[2,2,2] diene as the ligand and water as the proton source. This exceptionally simple protocol provides a reliable and practical access to structurally important phenylalanine derivatives and α,α-di(arylmethyl)acetates in high yields (up to 99%) with good to excellent ee values (up to 99%).

15.
Parasit Vectors ; 13(1): 94, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085719

RESUMO

BACKGROUND: New therapeutic drugs are urgently needed against visceral leishmaniasis because current drugs, such as pentavalent antimonials and miltefosine, produce severe side effects and development of resistance. Whether cyclosporine A (CsA) and its derivatives can be used as therapeutic drugs for visceral leishmaniasis has been controversial for many years. METHODS: In this study, we evaluated the efficacy of CsA and its derivative, dihydrocyclosporin A (DHCsA-d), against promastigotes and intracellular amastigotes of Leishmania donovani. Sodium stibogluconate (SSG) was used as a positive control. RESULTS: Our results showed that DHCsA-d was able to inhibit the proliferation of L. donovani promastigotes (IC50: 21.24 µM and 12.14 µM at 24 h and 48 h, respectively) and intracellular amastigotes (IC50: 5.23 µM and 4.84 µM at 24 and 48 h, respectively) in vitro, but CsA treatment increased the number of amastigotes in host cells. Both DHCsA-d and CsA caused several alterations in the morphology and ultrastructure of L. donovani, especially in the mitochondria. However, DHCsA-d showed high cytotoxicity towards cells of the mouse macrophage cell line RAW264.7, with CC50 values of 7.98 µM (24 h) and 6.65 µM (48 h). Moreover, DHCsA-d could increase IL-12, TNF-α and IFN-γ production and decrease the levels of IL-10, IL-4, NO and H2O2 in infected macrophages. On the contrary, CsA decreased IL-12, TNF-α, and IFN-γ production and increased the levels of IL-10, IL-4, NO and H2O2 in infected macrophages. The expression of L. donovani cyclophilin A (LdCyPA) in promastigotes and intracellular amastigotes and the expression of cyclophilin A (CyPA) in RAW 264.7 cells were found to be significantly downregulated in the CsA-treated group compared to those in the untreated group. However, no significant changes in LdCyPA and CyPA levels were found after DHCsA-d or SSG treatment. CONCLUSIONS: Our findings initially resolved the dispute regarding the efficacy of CsA and DHCsA-d for visceral leishmaniasis treatment. CsA showed no significant inhibitory effect on intracellular amastigotes. DHCsA-d significantly inhibited promastigotes and intracellular amastigotes, but it was highly cytotoxic. Therefore, CsA and DHCsA-d are not recommended as antileishmanial drugs.


Assuntos
Antiprotozoários/farmacologia , Ciclosporina/farmacologia , Ciclosporinas/farmacologia , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/parasitologia , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-2/imunologia , Leishmania donovani/crescimento & desenvolvimento , Leishmania donovani/fisiologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Macrófagos/imunologia , Macrófagos/parasitologia , Camundongos , Células RAW 264.7
16.
Int J Cancer ; 146(9): 2563-2575, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31498891

RESUMO

Metastasis is the leading cause of death for non-small cell lung cancer (NSCLC) patients. However, how lung cancer cells invade blood vessels during metastasis remains unclear. Here, based on bioinformatics analyses, we found that PLEK2 might regulate NSCLC migration and vascular invasion. As little is known about the function of PLEK2 in NSCLC, we aimed to clarify this. We demonstrated that PLEK2 was significantly upregulated in transforming growth factor beta 1 (TGF-ß1)-treated NSCLC cells through ELK1 transcriptional activation, highly expressed in NSCLC tissues, and negatively correlated with NSCLC overall survival. Meanwhile, PLEK2 overexpression significantly promoted NSCLC epithelial-to-mesenchymal transition (EMT) and migration, human lung microvascular endothelial cells endothelial-to-mesenchymal transition (EndoMT), and the destruction of vascular endothelial barriers. Moreover, PLEK2 knockdown inhibited TGF-ß1-induced EMT and EndoMT. Furthermore, PLEK2 was found to directly interact with SHIP2 and target it for ubiquitination and degradation in NSCLC cells. Next, we confirmed that SHIP2 overexpression inhibits NSCLC EMT, migration and invasion and showed that PLEK2 overexpression can activate SHIP2-associated TGF-ß/PI3K/AKT signaling. Our results suggest that PLEK2 could be a novel prognostic marker and potential therapeutic target for NSCLC metastasis and vascular invasion.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/secundário , Endotélio Vascular/patologia , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/patologia , Proteínas de Membrana/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/metabolismo , Ubiquitina/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células , Endotélio Vascular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Membrana/genética , Camundongos , Camundongos Nus , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Prognóstico , Proteólise , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Front Immunol ; 11: 613957, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33488623

RESUMO

The Toll pathway plays an important role in defense against infection of various pathogenic microorganisms, including viruses. However, current understanding of Toll pathway was mainly restricted in mammal and some model insects such as Drosophila and mosquitoes. Whether plant viruses can also activate the Toll signaling pathway in vector insects is still unknown. In this study, using rice stripe virus (RSV) and its insect vector (small brown planthopper, Laodelphax striatellus) as a model, we found that the Toll pathway was activated upon RSV infection. In comparison of viruliferous and non-viruliferous planthoppers, we found that four Toll pathway core genes (Toll, Tube, MyD88, and Dorsal) were upregulated in viruliferous planthoppers. When the planthoppers infected with RSV, the expressions of Toll and MyD88 were rapidly upregulated at the early stage (1 and 3 days post-infection), whereas Dorsal was upregulated at the late stage (9 days post-infection). Furthermore, induction of Toll pathway was initiated by interaction between a Toll receptor and RSV nucleocapsid protein (NP). Knockdown of Toll increased the proliferation of RSV in vector insect, and the dsToll-treated insects exhibited higher mortality than that of dsGFP-treated ones. Our results provide the first evidence that the Toll signaling pathway of an insect vector is potentially activated through the direct interaction between Toll receptor and a protein encoded by a plant virus, indicating that Toll immune pathway is an important strategy against plant virus infection in an insect vector.

18.
Trials ; 20(1): 719, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831051

RESUMO

BACKGROUND: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction. METHODS/DESIGN: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine. DISCUSSION: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.


Assuntos
Alopecia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Neoplasias da Mama/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Soja/química , Adolescente , Adulto , Idoso , Alopecia/induzido quimicamente , Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Método Duplo-Cego , Feminino , Glycyrrhiza/química , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxoides/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
BMC Vet Res ; 15(1): 446, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818287

RESUMO

BACKGROUND: Leishmaniosis, a disease caused by pathogenic Leishmania parasites, remains an unresolved health problem in the New World and the Old World. It is well known that lizards can be infected by a subgenus of Leishmania parasites, i.e. Sauroleishmania, which is non-pathogenic to humans. However, evidence suggests that lizards may also harbor pathogenic Leishmania species including the undetermined Leishmania sp., discovered in our previous work. Leishmania DNA in lizard blood can be detected by using molecular methods, such as the polymerase chain reaction (PCR). RESULTS: Three hundred and sixteen lizards, representing 13 species of four genera, were captured for blood samples collection in Northwest China. Two reliable molecular markers (cytochrome b and heat shock protein 70 genes) were used for detection in the lizard blood samples, to confirm a widespread presence of pathogenic Leishmania parasites and the distribution pattern of Leishmania spp. in lizards from Northwest China. The PCR data indicated positive detection rate for Leishmania in all the tested lizards with an overall prevalence of 57.91% (183/316). Apart from lizard parasites like Leishmania tarentolae and Leishmania sp., several pathogenic Leishmania including L. turanica, L. tropica and L. donovani complex were identified by using phylogenetic analysis. Co-existence of different haplotypes was observed in most Leishmania DNA-positive lizards with an overall rate of 77.6% (142/183). Even mixed infections with different Leishmania species appeared to occur in the lizards with an overall rate of 37.7% (69/183). CONCLUSIONS: Lizards can harbor pathogenic Leishmania spp. Co-existence of different haplotypes or even species of Leishmania indicates mixed infections in natural lizard host. Lizards may contribute to the spread of Leishmania parasites. The pathogenic Leishmania species detected in lizards from Northwest China may be of great eco-epidemiological importance.


Assuntos
Leishmania/classificação , Leishmaniose/epidemiologia , Lagartos/parasitologia , Animais , China/epidemiologia , DNA de Protozoário/sangue , Haplótipos , Leishmania/genética , Lagartos/sangue , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
20.
Gland Surg ; 8(5): 557-568, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31741887

RESUMO

Background: Papillary thyroid cancer (PTC) has a strong propensity to metastasize to the cervical lymph nodes. Little was known currently about whether tumor's location would influence the risk of lymph node metastasis in PTC. Methods: The study enrolled PTC patients who underwent primary surgical therapy in our center for small unifocal tumor. The tumor's location was evaluated by ultrasound in three axes, three planes and 3D space. Logistic univariate and multivariate analysis were applied to explore the association between tumors' location and the risk of lymph node metastasis in PTC. Different localization methods of thyroid tumors were evaluated using ROC curve. Results: Totally 1,266 PTC patients were enrolled in this study. Univariate and multivariate analyses showed that gender, age, tumor size and tumor's location (in longitudinal axis, longitudinal sagittal plane, longitudinal coronal plane, sagittal coronal plane and 3D space) was associated with central lymph node dissection (CLND); gender, tumor size and tumor's location (in longitudinal axis, coronal axis, longitudinal sagittal plane, longitudinal coronal plane, sagittal coronal plane and 3D space) was related with lateral lymph node dissection (LLND) (P<0.05). In the ROC curve analysis, the 3D location showed the highest predictive value of lymph node metastasis (C-statistics: 0.724 for CLNM; 0.763 for LLNM). The middle posterior lateral (OR=2.575, P=0.028), inferior anterior central (OR=2.829, P=0.016), inferior posterior lateral (OR=2.759, P=0.039) and isthmus tumors (OR=4.526, P=0.001) were at a higher risk of CLNM, and the middle anterior central tumors (OR=0.102, P=0.015) were related with lower risk of LLNM. Conclusions: Stereotactic localization showed the highest predictive value of lymph node metastasis. The middle posterior lateral, inferior anterior central, inferior posterior lateral and isthmus tumors were at a higher risk of CLNM when compared to other locations. For such patients, careful preoperative evaluation of nodal status should be done.

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