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1.
Neurotoxicology ; 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32247646

RESUMO

Fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) is an extensively used carbamate insecticide. Its developmental neurotoxicity and the underlying mechanisms have not been well investigated. In this study, zebrafish embryos were exposed to various concentrations of BPMC from 6 hpf (hours post fertilization, hpf) to 120 hpf. BPMC induced developmental toxicity with reduced motility in larval zebrafish. The spinal cord neutrophil infiltration, increased ROS production, caspase 3 and 9 activation, central nerve and peripheral motor neuron damage, axon and myelin degeneration were observed in zebrafish treated with BPMC generally in a dose-dependent manner. The expression of eight marker genes for nervous system function or development, namely, a1-tubulin, shha, elavl3, gap43, syn2a, gfap, mbp and manf, was significantly downregulated following BPMC exposure. AChE activity reduction and ache gene expression suppression was also found significantly in BPMC-treated zebrafish. These results indicate that BPMC is highly toxic to zebrafish and that BPMC induces zebrafish developmental neurotoxicity through pathways involved in inflammation, oxidative stress, degeneration and apoptosis.

2.
Emerg Microbes Infect ; 9(1): 517-519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116136

RESUMO

We report a recent (2018) gonorrhoeal urethritis caused by a multidrug-resistant Neisseria gonorrhoeae strain in China. The isolated N. gonorrhoeae strain from a male and female pair expressed high-level resistance to spectinomycin (SPC), azithromycin, and other antibiotics but was sensitive to ceftriaxone. The SPC high-level resistance (MIC = 2048 mg/L) was due to a small deletion in rspE that caused two amino acid changes in ribosomal protein S5.


Assuntos
Farmacorresistência Bacteriana Múltipla , Neisseria gonorrhoeae/efeitos dos fármacos , Espectinomicina/farmacologia , China , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/metabolismo , Fenótipo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo
3.
Pediatr Transplant ; 24(2): e13618, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31944495

RESUMO

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood-derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus-associated late-onset hemorrhagic cystitis (BKV-HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV-HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106 /kg once a week until the symptoms improved. The median follow-up time was 1432 (89-2080) days. The median frequency of MSC infusion was 2 (1-3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36-56.9) ×108 /mL before MSC infusion and 2.67 (0-56.3) ×108 /mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease-free survival, and the incidence of relapse and acute and chronic graft-versus-host disease between the MSC infusion group and non-MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein-Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood-derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV-HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long-term infection, or survival of patients with leukemia.

4.
Biomolecules ; 9(11)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690058

RESUMO

In the current study, corn steep liquor (CSL) is evaluated as an ideal raw agro-material for efficient lipid and docosahexaenoic acid DHA production by Aurantiochytrium sp. Low CSL level in medium (nitrogen deficiency) stimulated the biosynthesis of lipids and DHA while inhibiting cellular growth. The transcriptomic profiles of the Aurantiochytrium sp. cells are analyzed and compared when cultured under high (H group), normal (N group), and low (L group) levels of CSL in the medium. The discriminated transcriptomic profiles from the three groups indicates that changes in CSL level in medium result in a global change in transcriptome of Aurantiochytrium sp. The overall de novo assembly of cDNA sequence data generated 61,163 unigenes, and 18,129 of them were annotated in at least one database. A total of 5105 differently expressed (DE) genes were found in the N group versus the H group, with 2218 downregulated and 2887 upregulated. A total of 3625 DE genes were found in the N group versus the L group, with 1904 downregulated and 1721 upregulated. The analysis and categorization of the DE genes indicates that the regulation mechanism of CSL involved in the perception and transduction of the limited nitrogen signal, the interactions between the transcription factors (TFs) and multiple downstream genes, and the variations in downstream genes and metabolites, in sequence, are illuminated for the first time in the current study.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1633-1640, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607325

RESUMO

OBJECTIVE: To investigate the effects of cytomegalovirus (CMV) DNA load on immune reconstitution and clinical outcomes of patients after unrelated cord blood transplantation (UCBT). METHODS: Eight-color flow cytometry was used to dynamically monitor the changes of peripheral blood lymphocyte subsets of 41 patients at one year after UCBT, and 10 healthy volunteers were enroled as controls. Patients were divided into two groups according to the DNA load of CMV (DNA copies <1000/ml and DNA copies ≥1000/ml). Comparative analyse of the effect of CMV DNA load on lymphocyte subsets and transplantation outcomes were carried out after transplantation. RESULTS: The high CMV DNA load group showed a faster and expanded T cell reconstitution, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.38×109 /L vs 0.25×109 /L, P=0.015 and 2.53×109 /L vs 1.36×109 /L, P=0.006, respectively). Further analysis of T cell subsets suggested that CD8+ T cells presented a higher and faster recovery in the high DNA load group, and the differences between the two groups were statistically significant at one and nine months after transplantation (0.20×109 /L vs 0.10×109 /L, P=0.038 and 1.62×109 /L vs 0.68×109 /L, P=0.003, respectively). In addition, there were no significant differences in levels of B cells, regulatory B cells and NK cells between the two groups. Outcomes after one- and a-half-year transplantation showed that there were no significant difference in relapse, non-relapse mortality and overall survival between the high and the low DNA load groups (7.7% vs 7.5%) (P=0.900) (15.4% vs 21.4%) (P=0.686) and (76.9% vs 78.6%) (P=0.889) respectively. CONCLUSION: The high CMV DNA load induces a faster and long-lasting expansion of T cells, mainly as the expansion of CD8+ T cells after UCBT. Besides, under the current pre-emptive treatment of CMV, the high CMV DNA load does not affect the early survival of patients with acute myeloid leukemia after UCBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Linfócitos T CD8-Positivos , Citomegalovirus , DNA , Humanos
6.
Infect Drug Resist ; 12: 2471-2476, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496761

RESUMO

Purpose: Gentamicin is a promising antimicrobial for the treatment of gonorrhea. The study aimed to evaluate gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae isolates in China. Methods: In this study, the agar dilution method was used to determine the MICs of 470 isolates collected in 2016 to four effective antimicrobials (gentamicin, azithromycin, ceftriaxone, and spectinomycin). Results: Gentamicin MICs ranged from 1 to 8 mg/L. No isolate was resistant to gentamicin. Of seven isolates simultaneously resistant to azithromycin and ceftriaxone, 6 isolates demonstrated MICs of 4 mg/L or less to gentamicin. No cross relationships were found between MICs of gentamicinand susceptibility profiles of azithromycin, ceftriaxone, and spectinomycin. Conclusion: The in vitro results suggest that gentamicin can be a promising treatment option for gonococcal infections in China. Clinical trials to evaluate the therapeutic efficacy of gentamicin are required.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1246-1252, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418388

RESUMO

OBJECTIVE: To analyze the clinical outcomes of engraftment, graft-versus-host disease (GVHD) and survival in the patients with AML1-ETO positive acute myeloid leukemia (AML) treated with unrelated umbilical cord blood transplantation (UCBT). METHODS: Forty-Five patients with high-risk refractory AML1-ETO positive AML were treated with a single UCBT in a single center from July 2010 to April 2018. All the patients underwent a myeloablative preconditioning regimen,and cyclosporine A (CSA) combined with mycophenolate mofetil (MMF) was used to prevent GVHD. RESULTS: The median value of total nucleated cells (TNC) in cord blood was 5.21 (1.96-12.68)×107/kg recipient body weight, and that of CD34+ cells was 5.61 (0.56-15.4)×105/kg recipient weight. The implantation rate of neutrophil at 42 d and that of platelet at 120 d were 95.6% and 86.7%, respectively. The median time of absolute neutrophil count (ANC)>0.5×109/L and platelet 20×109/L were 16 (12-18) d and 37 (17-140) d after transplantation, respectively. The cumulative incidence of Ⅰ -Ⅳ grade acute GVHD (aGVHD) at 100 d after transplantation was 48.9% (95% CI 33.5%-62.6%), Ⅱ-Ⅳ grade aGVHD occurred in 12 cases (33.3%) (95% CI 20%-47.2%) , and Ⅲ-Ⅳ grade a GVHD in 8 cases (20%) (95% CI 9.8% -32.8%). In 5 cases of 40 patients survived over 100 days, the chronic GVHD (cGVHD) occurred after transplantation, among which 4 were localized, and 1 was extensive. 3 patients relapsed, and the 2-year cumulative relapse rate was 9.5% (95% CI 2.4%-22.8%). The median follow-up time was 23.5 (0.9-89.67) months, 10 patients died, 2-year disease-free survival rate (DFS) was 72.7%, and overall survival rate (OS) was 75.5%. Multivariate analysis showed that Ⅲ-Ⅳ. acute GVHD (aGVHD) affected overall survival. CONCLUSION: UCBT is an effective rescue treatment for patients with high-risk refractory AML1-ETO positive AML.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda , Transplante de Células-Tronco de Sangue Periférico , Subunidade alfa 2 de Fator de Ligação ao Core , Humanos , Ácido Micofenólico , Proteínas de Fusão Oncogênica , Proteína 1 Parceira de Translocação de RUNX1 , Condicionamento Pré-Transplante
8.
J Pharmacol Toxicol Methods ; 98: 106585, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31112751

RESUMO

RAR-related orphan receptor-γt (RORγt) directs differentiation of proinflammatory T helper 17 cells and is a potential therapeutic target for chronic autoimmune and inflammatory diseases including multiple sclerosis. In this study, zebrafish at days post fertilization treated with ethidium bromide (EB) at a concentration of 75 µM for 72 h were determined as the optimum conditions for the demyelination model development. Zebrafish motility was recorded automatically using a video-track motion detector and quantitative myelin assay was measured by FluoroMyelin staining. A well-known remyelination agent thyroxine (T4) was tested to confirm whether EB-induced motility and myelin damage could be rescued. Two RORγt lead inhibitors GSK805 and SR1001 were assessed for their therapeutic effects on remyelination, axon regeneration, motor neuron promotion and anti-inflammation. T4 significantly improved EB-induced motility dysfunction and myelin damage and promoted myelin basic protein (MBP) regeneration in the demyelinated zebrafish. GSK805 and SR1001 enhanced remyelination in a dose-dependent manner and promoted MBP regeneration. Both GSK805 and SR1001 markedly recovered EB-induced axon and motor neuron damage, and exhibited significantly inhibitory effects of neutrophil infiltration and macrophage recruitment. These results indicate that EB treatment can induce zebrafish demyelination; and the zebrafish demyelination model in combination with quantitative motility and myelin assays is a predictive, reproducible and relatively high throughput screening for rapidly in vivo identification of remyelination compounds and RORγt inhibitors.


Assuntos
Doenças Desmielinizantes/tratamento farmacológico , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Remielinização/efeitos dos fármacos , Peixe-Zebra/fisiologia , Animais , Animais Geneticamente Modificados , Axônios/efeitos dos fármacos , Modelos Animais de Doenças , Etídio/farmacologia , Proteína Básica da Mielina , Bainha de Mielina/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos
9.
Sci Rep ; 9(1): 4541, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30872660

RESUMO

Furanodiene is a natural terpenoid isolated from Rhizoma Curcumae, a well-known Chinese medicinal herb that presents anticancer effects in various types of cancer cell lines. In this study, we have successfully established zebrafish xenografts with 5 various human cancer cell lines; and validated these models with anti-cancer drugs used clinically for treating human cancer patients. We found that Furanodiene was therapeutically effective for human JF 305 pancreatic cancer cells and MCF-7 breast cancer cells xenotranplanted into zebrafish. Furanodiene showed a markedly synergistic anti-cancer effect when used in combination with 5-FU (5-Fluorouracil) for both human breast cancer MDA-MB-231 cells and human liver cancer BEL-7402 cells xenotransplanted into zebrafish. Unexpectedly, Furanodiene reversed multiple drug resistance in the zebrafish xenotransplanted with cis-Platinum-resistant human non-small cell lung cancer cells and Adriamycin-resistant human breast cancer cells. Furanodiene played its anti-cancer effects through anti-angiogenesis and inducing ROS production, DNA strand breaks and apoptosis. Furanodiene suppresseed efflux transporter Pgp (P-glycoprotein) function and reduced Pgp protein level, but no effect on Pgp related gene (MDR1) expression. These results suggest sensitizition and synergistic anti-cancer effects of Furanodiene that is worthy of a further investigation.

10.
Emerg Infect Dis ; 25(7): 1427-1429, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30900979

RESUMO

In 2016, we identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in China. The strain genotype was identical to the resistant clone FC428 that originated in Japan. Enhanced international collaborative surveillance programs are crucial to track the transmission of the ceftriaxone-resistant clones.


Assuntos
Antibacterianos/farmacologia , Ceftriaxona/farmacologia , Farmacorresistência Bacteriana , Gonorreia/epidemiologia , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , China/epidemiologia , Resistencia a Medicamentos Antineoplásicos , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Neisseria gonorrhoeae/classificação , Neisseria gonorrhoeae/genética
11.
J Agric Food Chem ; 67(19): 5560-5570, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30901205

RESUMO

The phytohormone 6-benzylaminopurine (6-BAP) significantly improves lipid synthesis of oleaginous microorganisms with the great potential applied in lipid production. In the current study, the lipid and DHA productions in oleaginous Aurantiochytrium sp. were found to be improved by 48.7% and 55.3%, respectively, induced by 6-BAP treatments. Then, using high-throughput RNA-seq technology, the overall de novo assembly of the cDNA sequence data generated 53871 unigenes, and 15902 of these were annotated in at least one database. The comparative transcriptomic profiles of cells with and without 6-BAP treatments revealed that a total of 717 were differently expressed genes (DE), with 472 upregulated and 245 downregulated. Further annotation and categorization indicated that some DE genes were involved in pathways crucial to lipid and DHA productions, such as fatty acid synthesis, central carbon metabolism, transcriptional factor, signal transduction, and mevalonate pathway. A regulation mode of 6-BAP, in turn, perception and transduction of 6-BAP signal, transcription factor, expression regulations of the downstream genes, and metabolic changes, respectively, was put forward for the first time in the present study. This research illuminates the transcriptomic mechanism of phytohormone stimulation of lipid and DHA production in an oleaginous microorganism and provides the potential targets modified using genetic engineering for improving lipid and DHA productivity.


Assuntos
Compostos de Benzil/farmacologia , Ácidos Docosa-Hexaenoicos/biossíntese , Metabolismo dos Lipídeos/efeitos dos fármacos , Reguladores de Crescimento de Planta/farmacologia , Purinas/farmacologia , Estramenópilas/efeitos dos fármacos , Estramenópilas/genética , Compostos de Benzil/química , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Reguladores de Crescimento de Planta/química , Purinas/química , Estramenópilas/metabolismo
12.
Aquat Toxicol ; 209: 34-41, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30685545

RESUMO

The potential risk and toxic mechanisms of fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) to animals and humans have not been fully elucidated. In this study, zebrafish embryos were exposed to various concentrations of BPMC from 48 hpf (hour post fertilization, hpf) to 72 hpf. We found that BPMC induced severe heart failure with bradycardia, reduced heart contractions, cardiac output and blood flow dynamics;and myocardial apoptosis. BPMC also induced cerebral hemorrhages and blood erythrocyte reduction in a dose-dependent manner. Also observed were increased ROS production and capase 9 and 3/7 activation. The mRNA levels of the ATPase-related gene (atp2a1l), calcium channel-related gene (cacna1ab), sodium channel-related gene (scn5Lab), potassium channel-related gene (kcnq1), the regulatory gene (tnnc1a) for cardiac troponin C, and several apoptosis-related genes were significantly downregulated in zebrafish following BPMC exposure. These results suggest that exposure to BPMC is a possible risk factor to cardiovascular and cerebrovascular systems in animals.


Assuntos
Carbamatos/toxicidade , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/complicações , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/complicações , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Caspases/metabolismo , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Dilatação Patológica , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Hiperemia/complicações , Espécies Reativas de Oxigênio/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
13.
Int J Biol Macromol ; 125: 1257-1265, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30240711

RESUMO

The mitochondrial genome (mitogenome) plays an important role in revealing molecular evolution. In this study, the complete mitogenome of Grammodes geometrica (G. geometrica) (Lepidoptera: Erebidae) was sequenced and characterized. The nucleotide composition of the genome is highly A + T biased, accounting for 80.49%. Most protein-coding genes (PCGs) are initiated by ATN codons except for the cytochrome oxidase subunit 1 (cox1) gene, which was initiated by CGA. The order and orientation of genes with the order trnM-trnI-trnQ-nad2 is a typical rearrangement compared with those ancestral insects in which trnM is located between trnQ and nad2. Most tRNA genes were folded into the typical cloverleaf structure except for trnS1 (AGN). The A + T-rich region contains the conserved motif "ATAGA" followed by a 19 bp poly-T stretch, which was also observed in other Noctuoidea species. In addition, we reconstructed phylogenetic trees among the nucleotide alignments of five families of Noctuoidea species except the Oenosandridae. Finally, we achieved a well-supported tree, which showed that G. geometrica belongs to the Erebidae family. Moreover, the relationships at the family-level can be displayed as follows: (Notodontidae + (Erebidae + (Nolidae + (Euteliidae + Noctuidae)))).


Assuntos
Genoma Mitocondrial , Genômica , Insetos/classificação , Insetos/genética , Mariposas/classificação , Mariposas/genética , Filogenia , Animais , Composição de Bases , Sequência de Bases , Biologia Computacional/métodos , Rearranjo Gênico , Genômica/métodos , Anotação de Sequência Molecular , Fases de Leitura Aberta
14.
Acta Pharmacol Sin ; 40(7): 980-988, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30382184

RESUMO

Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer. In this study we investigated the metabolism and disposition of pyrotinib in six healthy Chinese men after a single oral dose of 402 mg of [14C]pyrotinib. At 240 h postdose, the mean cumulative excretion of the dose radioactivity was 92.6%, including 1.7% in urine and 90.9% in feces. In feces, oxidative metabolites were detected as major drug-related materials and the primary metabolic pathways were O-depicoline (M1), oxidation of pyrrolidine (M5), and oxidation of pyridine (M6-1, M6-2, M6-3, and M6-4). In plasma, the major circulating entities identified were pyrotinib, SHR150980 (M1), SHR151468 (M2), and SHR151136 (M5), accounting for 10.9%, 1.9%, 1.0%, and 3.0%, respectively, of the total plasma radioactivity based on the AUC0-∞ ratios. Approximately 58.3% of the total plasma radioactivity AUC0-∞ was attributed to covalently bound materials. After incubation of human plasma with [14C]pyrotinib at 37 °C for 2, 5, 8, and 24 h, the recovery of radioactivity by extraction was 97.4%, 91.8%, 69.6%, and 46.7%, respectively, revealing covalent binding occurred independently of enzymes. A group of pyrotinib adducts, including pyrotinib-lysine and pyrotinib adducts of the peptides Gly-Lys, Lys-Ala, Gly-Lys-Ala, and Lys-Ala-Ser, was identified after HCl hydrolysis of the incubated plasma. Therefore, the amino acid residue Lys190 of human serum albumin was proposed to covalently bind to pyrotinib via Michael addition. Finally, the covalently bound pyrotinib could dissociate from the human plasma protein and be metabolized by oxidation and excreted via feces.


Assuntos
Acrilamidas/metabolismo , Aminoquinolinas/metabolismo , Antineoplásicos/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Albumina Sérica Humana/metabolismo , Acrilamidas/química , Acrilamidas/farmacocinética , Adulto , Aminoquinolinas/química , Aminoquinolinas/farmacocinética , Antineoplásicos/química , Antineoplásicos/farmacocinética , Análise Química do Sangue , Radioisótopos de Carbono , Fezes/química , Humanos , Masculino , Orosomucoide/metabolismo , Ligação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética , Albumina Sérica Humana/química , Urina/química
15.
Fish Shellfish Immunol ; 83: 272-282, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30217505

RESUMO

The mudflat crab Helice tientsinensis is one of the most economically important aquaculture species in China. Nevertheless, it is susceptible to various diseases caused by viruses, bacteria and rickettsia-like organisms. A better understanding of the immune system and genes related to the responses to bacterial and viral infection is required. Herein, the hepatopancreas transcriptome of H. tientsinensis was analyzed by comparing control and lipopolysaccharide (LPS)-stimulated RNA-Seq data, yielding 91,885,038 bp and 13.78 Gb of clean reads. Following assembly and annotation, 93,207 unigenes with an average length of 883 bp were identified, of which 31,674 and 13,700 were annotated in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. Following LPS, 4845 differentially expressed genes (DEGs) were identified, of which 2491 and 2354 were up- and down-regulated, respectively. To further investigate immune-related DEGs, KEGG enrichment analysis identified immune response pathways, most notably the peroxisome and Toll-like receptor signaling pathways. Quantitative real time-PCR (qRT-PCR) confirmed the up-regulation of a random selection of DEGs. This systematic transcriptomic analysis of the innate immune pathway in H. tientsinensis expands our understanding of the immune system in crabs.


Assuntos
Proteínas de Artrópodes/genética , Braquiúros/genética , Braquiúros/imunologia , Hepatopâncreas/metabolismo , Animais , Perfilação da Expressão Gênica , Lipopolissacarídeos/farmacologia
16.
Chin J Nat Med ; 16(7): 546-560, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30080653

RESUMO

The present study was designed to develop a practical strategy to tackle the problem of lacking standard compounds and limited references for identifying structure-related compounds in Streptocaulon griffithii Hook. f., especially those in trace concentrations, with a focus on antitumor activity. The cardiac glycosides (CGs)-enriched part was determined using in vitro bioactive assays in three cancer cell lines and then isolated using macroporous resins. The MS and MS/MS data were acquired using a high performance liquid chromatography coupled with hybrid quadrupole-time of flight (HPLC-Q-TOF-MS) system. To acquire data of trace compound in the extract, a multiple segment program was applied to modify the HPLC-Q-TOF-MS method. A mass defect filter (MDF) approach was employed to make a primary MS data filtration. Utilizing a MATLAB program, the redundant peaks obtained by imprecise MDF template calculated with limited references were excluded by fragment ion classification, which was based on the ion occurrence number in the MDF-filtered total ion chromatograms (TIC). Additionally, the complete cleavage pathways of CG aglycones were proposed to assist the structural identification of 29 common fragment ions (CFIs, ion occurrence number ≥ 5) and diagnostic fragment ions (DFIs, ion occurrence number < 5). As a result, 30 CGs were filtered out from the MDF results, among which 23 were identified. This newly developed strategy may provide a rapid and effective tool for identifying structure-related compounds in herbal medicines.


Assuntos
Apocynaceae/química , Glicosídeos Cardíacos/farmacologia , Biologia Computacional , Mineração de Dados , Medicamentos de Ervas Chinesas/farmacologia , Espectrometria de Massas em Tandem , Células A549 , Animais , Glicosídeos Cardíacos/química , Glicosídeos Cardíacos/isolamento & purificação , Glicosídeos Cardíacos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Humanos , Concentração Inibidora 50 , Células MCF-7 , Camundongos , Estrutura Molecular , Raízes de Plantas/química , Plantas Medicinais/química , Fluxo de Trabalho
17.
Int J Biol Macromol ; 118(Pt B): 1574-1583, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29981329

RESUMO

In the present study, the complete mitochondrial genome (mitogenome) of Clostera anastomosis (C. anastomosis) has been determined for the first time. The mitogenome is 15,390 base pairs (bp) in length, comprised of 13 protein-coding genes (PCGs), 2 ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs) and one non-coding control region (CR). The gene order shows a typical trnM rearrangement (trnM-trnI-trnQ) compared to ancestral insects (trnI-trnQ-trnM). Almost all the PCGs have the same start codon (ATN) except for cox1 (CGA), and almost all tRNAs have a typical cloverleaf secondary structure except for trnS1. At the beginning of the CR, we found a conserved motif "ATAGA + poly-T" as found in other lepidopteran insects. There are 20 intergenic regions and 11 overlapping regions, ranging from 1 to 53 bp and 1 to 9 bp, respectively. The A + T content is relatively high across the whole mitogenome. The optimal tree topologies of Noctuoidea were given by the dataset consisting of all 13 PCGs from five families (exclude Oenosandridae). Our trees suggested a topology of (Notodontidae + (Erebidae + (Nolidae + (Euteliidae + Noctuidae)))) and identified that C. anastomosis belongs to Notodontidae.


Assuntos
Genoma Mitocondrial/genética , Lepidópteros/classificação , Lepidópteros/genética , Filogenia , Animais , Composição de Bases , Pareamento de Bases , Sequência de Bases , Rearranjo Gênico , RNA Ribossômico/genética , RNA de Transferência/genética
18.
J Agric Food Chem ; 66(30): 8132-8141, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29975524

RESUMO

The growth and development of the Chinese oak silkworm, Antheraea pernyi, are strongly influenced by environmental conditions, including heavy metal pollution. An excess of heavy metals causes cellular damage through the production of free radical reactive oxygen species. In this study, transcriptome analysis was performed to investigate global gene expression when A. pernyi was exposed to zinc infection. With RNA sequencing (RNA-Seq), a total of 25 795 510 and 38 158 855 clean reads were obtained from zinc-treated and control fat body libraries, respectively. We identified 2399 differential expression genes (DEGs) (1845 upregulated and 544 downregulated genes) in the zinc-treated library. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these DEGs were related to the peroxisome pathway that was associated with antioxidant defense. Our results suggest that fat bodies of A. pernyi constitute a strong antioxidant defense against heavy metal contamination.


Assuntos
Antioxidantes/metabolismo , Bombyx/efeitos dos fármacos , Bombyx/genética , Proteínas de Insetos/genética , Zinco/toxicidade , Animais , Bombyx/crescimento & desenvolvimento , Bombyx/metabolismo , Perfilação da Expressão Gênica , Proteínas de Insetos/metabolismo , Transcriptoma
19.
Zebrafish ; 15(3): 243-253, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29653073

RESUMO

Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 µM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p < 0.05, p < 0.01, and p < 0.001) in the zebrafish model. The larval zebrafish heart failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.


Assuntos
Fármacos Cardiovasculares/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Insuficiência Cardíaca/tratamento farmacológico , Peixe-Zebra/crescimento & desenvolvimento , Animais , Sistemas de Liberação de Medicamentos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Peixe-Zebra/fisiologia
20.
PLoS Med ; 15(2): e1002499, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29408881

RESUMO

BACKGROUND: Gonorrhea remains one of the most common sexually transmitted diseases worldwide. Successful treatment has been hampered by emerging resistance to each of the antibiotics recommended as first-line therapies. We retrospectively analyzed the susceptibility of gonorrhea to azithromycin and ceftriaxone using data from the China Gonococcal Resistance Surveillance Programme (China-GRSP) in order to provide evidence for updating the treatment recommendations in China. METHODS AND FINDINGS: In this study, we included 3,849 isolates collected from patients with a confirmed positive Neisseria gonorrhoeae (N. gonorrhoeae) culture at clinic visits during the period of 1 January 2013 through 31 December 2016 in 7 provinces. Antimicrobial susceptibility testing of gonorrhea isolates using agar dilution was conducted to determine minimum inhibitory concentration (MIC). Resistance to azithromycin (RTA) was defined as MIC ≥ 1.0 mg/l, and decreased susceptibility to ceftriaxone (DSC) was defined as MIC ≥ 0.125 mg/l. The prevalence of isolates with RTA was 18.6% (710/3,827; 95% CI 17.4%-19.8%). The percentage of patients with DSC fluctuated between 9.7% and 12.2% over this period. The overall prevalence of isolates with both RTA and DSC was 2.3% (87/3,827; 95% CI 1.9%-2.8%) and it increased from 1.9% in 2013 to 3.3% in 2016 (chi-squared test for trend, P = 0.03). Study limitations include the retrospective study design and potential biases in the sample, which may overrepresent men with symptomatic infection, coastal residents, and people reporting as heterosexual. CONCLUSIONS: To our knowledge, this is the first national study on susceptibility of N. gonorrhoeae to azithromycin and ceftriaxone in China. Our findings indicate high rates of RTA and DSC from 2013 to 2016. Although dual therapy with azithromycin and ceftriaxone has been recommended by WHO and many countries to treat gonorrhea, reevaluation of this therapy is needed prior to its introduction in China.


Assuntos
Azitromicina/uso terapêutico , Ceftriaxona/uso terapêutico , Farmacorresistência Bacteriana , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , China/epidemiologia , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/patogenicidade , Prevalência , Estudos Retrospectivos
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