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1.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

2.
Sci Adv ; 7(29)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34272237

RESUMO

Unconventional superconductivity and, in particular, triplet superconductivity have been front and center of topological materials and quantum technology research. Here, we report our observation of triplet pairing in nonmagnetic CoSi2/TiSi2 heterostructures on silicon. CoSi2 undergoes a sharp superconducting transition at a critical temperature T c ≃ 1.5 K, while TiSi2 is a normal metal. We investigate conductance spectra of both two-terminal CoSi2/TiSi2 contact junctions and three-terminal T-shaped CoSi2/TiSi2 superconducting proximity structures. Below T c, we observe (i) a narrow zero-bias conductance peak on top of a broad hump, accompanied by two symmetric side dips in the contact junctions, (ii) a narrow zero-bias conductance peak in T-shaped structures, and (iii) hysteresis in the junction magnetoresistance. These three independent and complementary observations point to chiral p-wave pairing in CoSi2/TiSi2 heterostructures. The excellent fabrication compatibility of CoSi2 and TiSi2 with present-day silicon-based integrated-circuit technology suggests their potential use in scalable quantum-computing devices.

3.
Front Microbiol ; 12: 691008, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220783

RESUMO

Dengue virus (DENV) infection can lead to a complex spectrum of clinical outcomes, ranging from asymptomatic infection to life-threatening severe dengue. The reasons for thus drastically varying manifestations of the disease remain an enigma. Herein, we reported an original discovery of the synergistic effect between preexisting Epstein-Barr virus (EBV) infection and DENV superinfection in vitro and of a strong correlation of these two viruses in the clinical samples from dengue patients. We showed that (I) DENV-2 infection of an EBV-positive cell line (EBV + Akata cell) reactivated EBV, and it could be blocked by wortmannin treatment. (II) Examination of human peripheral blood mononuclear cell (PBMC) samples from dengue patients revealed significantly elevated cell-associated EBV DNA copy number at the time of hospitalization vs. at the time of disease recovery in most individuals. (III) EBV infection promoted DENV propagation in both EBV-hosting B cells and indirectly in THP-1 cells, supported by the following evidence: (A) EBV + Akata cells were more permissive to DENV-2 infection compared with Akata cells harboring no EBV virus (EBV- Akata cells). (B) Low-molecular weight fraction secreted from EBV + Akata cells could enhance DENV-2 propagation in monocytic THP-1 cells. (C) While reactivation of EBV in EBV + Akata cells further increased DENV-2 yield from this cell line, pharmacological inhibition of EBV replication by acyclovir had the opposite effect. To our knowledge, this is the first investigation demonstrating a positive correlation between EBV and DENV in vitro and in human biospecimens.

4.
Sci Rep ; 11(1): 8155, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854110

RESUMO

There is tremendous interest in measuring the strong electron-phonon interactions seen in topological Weyl semimetals. The semimetal NbIrTe4 has been proposed to be a Type-II Weyl semimetal with 8 pairs of opposite Chirality Weyl nodes which are very close to the Fermi energy. We show using polarized angular-resolved micro-Raman scattering at two excitation energies that we can extract the phonon mode dependence of the Raman tensor elements from the shape of the scattering efficiency versus angle. This van der Waals semimetal with broken inversion symmetry and 24 atoms per unit cell has 69 possible phonon modes of which we measure 19 modes with frequencies and symmetries consistent with Density Functional Theory calculations. We show that these tensor elements vary substantially in a small energy range which reflects a strong variation of the electron-phonon coupling for these modes.

5.
Phys Rev Lett ; 124(18): 186602, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32441947

RESUMO

We report theoretical and experimental analyses of the thermal Hall conductivity in correlated systems. For both fermionic and bosonic excitations with nontrivial topology, we show that at "intermediate" temperatures, the thermal Hall conductivity exhibits an unexpected universal scaling with a simple exponential form. At low temperatures, it behaves differently and reflects the spectral properties of underlying excitations. Our predictions are examined as examples in two prototype compounds, the quantum paraelectric SrTiO_{3} and the spin-liquid compound RuCl_{3}. The experimental data can be largely covered by our proposed minimal phenomenological model independent of microscopic details, revealing dominant bosonic contributions in SrTiO_{3} and gapped fermionic excitations in RuCl_{3}. Our work establishes a phenomenological link between microscopic models and experimental data and provides a unified basis for analyzing the thermal Hall conductivity in correlated systems over a wide temperature region.

6.
Emerg Microbes Infect ; 9(1): 962-975, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32267217

RESUMO

The H7N9 virus mutated in 2017, resulting in new cases of highly pathogenic avian influenza (HPAI) H7N9 virus infection. H7N9 was found in a viraemic patient in Guangdong province, China. The present study aimed to clarify the pathogenic characteristics of HPAI H7N9. Virus was isolated from the plasma and sputum of the patient with HPAI H7N9. Liquid phase chip technology was used to detect the plasma cytokines from the infected patient and healthy controls. Mice were infected with strains A/Guangdong/GZ8H002/2017(H7N9) and A/Zhejiang/DTID-ZJU01/2013(H7N9) to observe the virus's pathogenic characteristics. Serum and brain tissue were collected at 2, 4, and 6 days after infection. The viruses in serum and brain tissue were detected and isolated. The two strains were infected into A549 cells, exosomes were extracted, and virus genes in the exosomes were assessed. Live virus was isolated from the patient's plasma. An acute cytokine storm was detected during the whole course of the disease. In animal experiments, A/Guangdong/GZ8H002/2017(H7N9) was more pathogenic than A/Zhejiang /DTID-ZJU01/2013(H7N9) and resulted in the death of mice. Live virus was isolated from infected mouse serum. Virus infection was also detected in the brain of mice. Under viral stress, A549 cells secreted exosomes containing the entire viral genome. The viraemic patient was confirmed to have an HPAI H7N9 infection. A/Guangdong/GZ8H002/2017(H7N9) showed significantly enhanced toxicity. Patient deaths might result from cytokine storms and brain infections. Extrapulmonary tissue infection might occur via the exosome pathway. The determined pathogenic characteristics of HPAI H7N9 will contribute to its future treatment.


Assuntos
Exossomos/virologia , Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária/virologia , Influenza Humana/virologia , Animais , Aves , Sangue/virologia , Encéfalo/virologia , Linhagem Celular , Citocinas/sangue , Genoma Viral , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Subtipo H7N9 do Vírus da Influenza A/imunologia , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Camundongos , Viremia
7.
Sci Adv ; 6(9): eaay0443, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32158938

RESUMO

The iron-based superconductor FeTe x Se1-x is one of the material candidates hosting Majorana vortex modes residing in the vortex cores. It has been observed by recent scanning tunneling spectroscopy measurement that the fraction of vortex cores having zero-bias peaks decreases with increasing magnetic field on the surface of FeTe x Se1-x . The hybridization of two Majorana vortex modes cannot simply explain this phenomenon. We construct a three-dimensional tight-binding model simulating the physics of over a hundred Majorana vortex modes in FeTe x Se1-x . Our simulation shows that the Majorana hybridization and disordered vortex distribution can explain the decreasing fraction of the zero-bias peaks observed in the experiment; the statistics of the energy peaks off zero energy in our Majorana simulation are in agreement with the experiment. These agreements lead to an important indication of scalable Majorana vortex modes in FeTe x Se1-x . Thus, FeTe x Se1-x can be one promising platform having scalable Majorana qubits for quantum computing.

8.
Infect Dis Poverty ; 9(1): 17, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32114982

RESUMO

BACKGROUND: Dengue is a re-emerging public health problem and mosquito-borne infectious disease that is transmitted mainly by Aedes aegypti and Ae. albopictus. Early diagnosis, isolation, and treatment of patients are critical steps for dengue epidemic control, especially to prevent secondary transmission of dengue virus (DENV). However, little is known about defervescent dengue patients as a source of infection. METHODS: This case study describes 1268 dengue patients hospitalized at Guangzhou Eighth People's Hospital from June 2013 to December 2014. The viral loads of each individual were measured using real-time reverse transcription-polymerase chain reaction. Ae. aegypti and Ae. albopictus were exposed to blood meal with gradated dengue viral loads to characterize the relationship between viremia in dengue patients and the vector competence of vector mosquitoes. RESULTS: The viral numbers in the blood were measured, ranging from 108 to 103 copies/ml from day 1 to day 12 after fever onset. Vector competence analysis of Ae. aegypti and Ae. albopictus indicated that viremia > 104 copies/ml can still infect vector mosquitoes, which implied that the defervescent dengue patients might be a source of infection. CONCLUSIONS: The results of this study indicate that some defervescent dengue patients still have sufficient viral load to infect vector mosquitoes. Therefore, the protection against mosquito biting for these people should be extended to prevent secondary transmission events.


Assuntos
Vírus da Dengue/fisiologia , Dengue/epidemiologia , Dengue/transmissão , Mosquitos Vetores/virologia , Aedes/virologia , Animais , Vírus da Dengue/isolamento & purificação , Humanos , Carga Viral
9.
BMC Infect Dis ; 19(1): 926, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675923

RESUMO

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play immunosuppressive roles in cancers and some infectious diseases; however, their role in dengue fever (DF) remains unknown. This study evaluated the clinical significance of MDSCs in DF patients. METHODS: This study comprised 178 non-severe DF patients, 20 non-dengue fever (NDF) controls, and 30 healthy donors. The DF patients were divided into the following five groups based on the fever duration from its onset to the day of sample collection: fever duration of 1-2, 3-4, 5-6, 7-8, and > 9 days. Among these DF patients, 14 were monitored for eight days, and their peripheral blood samples were collected every two days. The mononuclear cells were isolated and analyzed using flow cytometry. The correlation between the MDSCs and clinical and immunological indicators of the DF patients was evaluated using Spearman analysis. RESULTS: The count of the peripheral blood MDSCs, especially monocytic MDSCs, of the 178 DF patients were dramatically higher than those of the NDF and healthy controls, and remarkably decreased with the fever duration. Moreover, the MDSC count correlated with some indicators, including the dengue viral load (rho = 0.367, p < .001), body temperature (rho = 0.263, p = .005), prothrombin time (rho = 0.475, p < .001), CD4+ T cell number (rho = - 0.317, p < .001), CD8+ T cell number (rho = - 0.361, p < .001), "programmed cell death protein 1" (PD-1) (rho = - 0.347, p < .001), "T cell immunoglobulin domain and mucin domain-3" (Tim3) (rho = - 0.258, p = .001), interferon-α (IFN-α) (rho = 0.43, p < .001), and "regulated upon activation normal T-cell expressed and secreted" (RANTES) (rho = 0.278, p = .019). Furthermore, the level of arginase-1, but not nitric oxide, was higher in the DF patients than in the healthy controls and was closely related to the number of MDSCs (rho = 0.265, p = .024). CONCLUSIONS: Our study reveals a significant correlation between MDSCs and DF clinical indicators, posing MDSCs as potential target cells for DF treatment.


Assuntos
Dengue/etiologia , Células Supressoras Mieloides/patologia , Adolescente , Adulto , Arginase/sangue , Linfócitos T CD4-Positivos/patologia , Estudos de Casos e Controles , Estudos Transversais , Dengue/sangue , Feminino , Citometria de Fluxo , Humanos , Interferon-alfa/sangue , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Óxido Nítrico/sangue , Prognóstico , Fatores de Tempo , Carga Viral , Adulto Jovem
10.
Phys Rev Lett ; 123(2): 027003, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31386504

RESUMO

We study vortex bound states in three-dimensional (3D) superconducting Dirac semimetals with time reversal symmetry. We find that there exist robust gapless vortex bound states propagating along the vortex line in the s-wave superconducting state. We refer to this newly found phase as the quasi-1D nodal vortex line phase. According to the Altland-Zirnbauer classification, the phase is characterized by a topological index (ν;N) at k_{z}=0 and k_{z}=π, where ν is the Z_{2} topological invariant for a 0D class-D system and N is the Z topological invariant for a 0D class-A system. Furthermore, we show that the vortex end Majorana zero mode can coexist with the quasi-1D nodal phase in certain types of Dirac semimetals. The possible experimental observations and material realization of such nodal vortex line states are discussed.

11.
J Virol ; 93(8)2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30728253

RESUMO

Animal models of Zika virus (ZIKV) infection have recently been established in mice, guinea pigs, and nonhuman primates. Tree shrews (Tupaia belangeri) are an emerging experimental animal in biomedical applications, but their susceptibility to ZIKV infection has not been explored. In the present study, we show that subcutaneous inoculation of ZIKV led to rapid viremia and viral secretion in saliva, as well as to typical dermatological manifestations characterized by massive diffuse skin rash on the trunk. Global transcriptomic sequencing of peripheral blood mononuclear cells isolated from ZIKV-infected animals revealed systematic gene expression changes related to the inflammatory response and dermatological manifestations. Importantly, ZIKV infection readily triggered the production of high-titer neutralizing antibodies, thus preventing secondary homologous infection in tree shrews. However, neonatal tree shrews succumbed to ZIKV challenge upon intracerebral infection. The tree shrew model described here recapitulates the most common dermatological manifestations observed in ZIKV-infected patients and may greatly facilitate the elucidation of ZIKV pathogenesis and the development of novel vaccines and therapeutics.IMPORTANCE The reemergence of Zika virus (ZIKV) has caused a global public health crisis since 2016, and there are currently no vaccines or antiviral drugs to prevent or treat ZIKV infection. However, considerable advances have been made in understanding the biology and pathogenesis of ZIKV infection. In particular, various animal models have been successfully established to mimic ZIKV infection and its associated neurological diseases and to evaluate potential countermeasures. However, the clinical symptoms in these mouse and nonhuman primate models are different from the common clinical manifestations seen in human ZIKV patients; in particular, dermatological manifestations are rarely recapitulated in these animal models. Here, we developed a new animal model of ZIKV infection in tree shrews, a rat-sized, primate-related mammal. In vitro and in vivo characterization of ZIKV infection in tree shrews established a direct link between ZIKV infection and the immune responses and dermatological manifestations. The tree shrew model described here, as well as other available animal models, provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccines and therapeutics.


Assuntos
Dermatopatias Virais , Tupaia , Infecção por Zika virus , Zika virus/metabolismo , Animais , Linhagem Celular , Cricetinae , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/veterinária , Inflamação/virologia , Masculino , Saliva/metabolismo , Saliva/virologia , Dermatopatias Virais/metabolismo , Dermatopatias Virais/patologia , Dermatopatias Virais/veterinária , Dermatopatias Virais/virologia , Tupaia/metabolismo , Tupaia/virologia , Viremia/metabolismo , Viremia/patologia , Viremia/virologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia , Infecção por Zika virus/veterinária
12.
Phys Rev Lett ; 122(2): 027002, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30720289

RESUMO

We use the functional renormalization group method to study a three-orbital model for superconducting Sr_{2}RuO_{4}. Although the pairing symmetry is found to be a chiral p wave, the atomic spin-orbit coupling induces near nodes for quasiparticle excitations. Our theory explains a major experimental puzzle between a d-wavelike feature observed in thermal experiments and the chiral p-wave triplet pairing revealed in nuclear-magnetic resonance and the Kerr effect.

13.
J Med Virol ; 91(5): 872-876, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30485459

RESUMO

Understanding of kinetics of antibody responses is crucial for developing rapid serological tests and studying the mechanisms of Zika virus (ZIKV) infection. Most of the serological diagnostic assays previously published are based on either IgM or IgG titer, little is known on the level of IgA antibody in saliva and urine. In this study, we investigated the kinetics of IgM/IgG/IgA antibody responses in serum, saliva, and urine obtained from two ZIKV infected individuals from as early as the second day of onset of symptoms to as long as 2 years postinfection. Other than detecting robust early IgM response, long lasting IgG response, we discovered strong early IgA response specific for ZIKV in saliva in both patients. This unique observation provides a novel strategy and scientific basis for the development of noninvasive rapid tests for ZIKV infection.


Assuntos
Anticorpos Antivirais/análise , Formação de Anticorpos , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Infecção por Zika virus/imunologia , Zika virus/imunologia , Adulto , Feminino , Humanos , Masculino , Saliva/imunologia , Soro/imunologia , Urinálise
14.
Natl Sci Rev ; 6(2): 195, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34691850
15.
Emerg Microbes Infect ; 7(1): 169, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30333476

RESUMO

Zika virus (ZIKV) has elicited global concern due to its unique biological features, unusual transmission routes, and unexpected clinical outcomes. Although ZIKV transmission through anal intercourse has been reported in humans, it remains unclear if ZIKV is detectable in the stool, if it can infect the host through the anal canal mucosa, and what the pathogenesis of such a route of infection might be in the mouse model. Herein, we demonstrate that ZIKV RNA can be recovered from stools in multiple mouse models, as well as from the stool of a ZIKV patient. Remarkably, intra-anal (i.a.) inoculation with ZIKV leads to efficient infection in both Ifnar1-/- and immunocompetent mice, characterized by extensive viral replication in the blood and multiple organs, including the brain, small intestine, testes, and rectum, as well as robust humoral and innate immune responses. Moreover, i.a. inoculation of ZIKV in pregnant mice resulted in transplacental infection and delayed fetal development. Overall, our results identify the anorectal mucosa as a potential site of ZIKV infection in mice, reveal the associated pathogenesis of i.a. infection, and highlight the complexity of ZIKV transmission through anal intercourse.


Assuntos
Fezes/virologia , Mucosa Intestinal/virologia , Reto/virologia , Eliminação de Partículas Virais , Infecção por Zika virus/virologia , Zika virus/fisiologia , Animais , Feminino , Humanos , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/imunologia , Complicações na Gravidez/virologia , Replicação Viral , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/genética , Infecção por Zika virus/imunologia
17.
Proc Natl Acad Sci U S A ; 115(33): 8311-8315, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30061416

RESUMO

Anomalous surface states with Fermi arcs are commonly considered to be a fingerprint of Dirac semimetals (DSMs). In contrast to Weyl semimetals, however, Fermi arcs of DSMs are not topologically protected. Using first-principles calculations, we predict that ß-cuprous iodide (ß-CuI) is a peculiar DSM whose surface states form closed Fermi pockets instead of Fermi arcs. In such a fermiological Dirac semimetal, the deformation mechanism from Fermi arcs to Fermi pockets stems from a large cubic term preserving all crystal symmetries and from the small energy difference between the surface and bulk Dirac points. The cubic term in ß-CuI, usually negligible in prototypical DSMs, becomes relevant because of the particular crystal structure. As such, we establish a concrete material example manifesting the lack of topological protection for surface Fermi arcs in DSMs.

18.
Sci Rep ; 8(1): 7853, 2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29777139

RESUMO

Sau, Lutchyn, Tewari and Das Sarma (SLTD) proposed a heterostructure consisting of a semiconducting thin film sandwiched between an s-wave superconductor and a magnetic insulator and showed possible Majorana zero mode. Here we study spin polarization of the vortex core states and spin selective Andreev reflection at the vortex center of the SLTD model. In the topological phase, the differential conductance at the vortex center contributed from the Andreev reflection, is spin selective and has a quantized value [Formula: see text] at zero bias. In the topological trivial phase, [Formula: see text] at the lowest quasiparticle energy of the vortex core is spin selective due to the spin-orbit coupling (SOC). Unlike in the topological phase, [Formula: see text] is suppressed in the Giaever limit and vanishes exactly at zero bias due to the quantum destruction interference.

19.
Cell Physiol Biochem ; 46(2): 633-643, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617693

RESUMO

BACKGROUND/AIMS: Since the first case of novel H7N9 infection was reported, China has experienced five epidemics of H7N9. During the fifth wave, a highly pathogenic H7N9 strain emerged. In order to assess whether the H7N9 vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) was effective in protecting against highly pathogenic H7N9, we conducted this study. METHODS: Groups of mice were immunized twice by intraperitoneal injection with 500 µl of either split vaccine alone or MF59-adjuvanted vaccine. Serum was collected 2 weeks after the second vaccine booster. The hemagglutinin inhibition test was conducted on vaccine seed and highly pathogenic H7N9 to evaluate the neutralization of highly pathogenic H7N9. We also immunized mice and challenged them with highly pathogenic H7N9. Mice were observed for illness, weight loss, and death at 1 week and 2 weeks post-infection. Then, the mice were sacrificed and lungs were removed. Antibody responses were assessed and pathological changes in the lung tissue were evaluated. RESULTS: The ability of serum to neutralize highly pathogenic H7N9 was reduced. In mice, highly pathogenic H7N9 was more virulent than A/Zhejiang/DTID-ZJU01/2013(H7N9). After challenge with highly pathogenic H7N9, all mice died while mice challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) all recovered. The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine was able to protect against infection with highly pathogenic H7N9 in mice, with or without MF59. Moreover, H7N9 vaccine adjuvanted with MF59 produced high antibody levels, which lead to better protection. CONCLUSIONS: The A/ZJU01/PR8/2013 split H7N9 avian influenza vaccine based on A/Zhejiang/DTID-ZJU01/2013(H7N9) is effective in protecting against highly pathogenic H7N9. H7N9 vaccine adjuvanted with MF59 offers better protection against infection with highly pathogenic H7N9. In order to make the H7N9 vaccine applicable to humans, further clinical trials are required to evaluate MF59 adjuvanted vaccine. Meanwhile, the vaccine strain should be updated based on the highly pathogenic H7N9 gene sequence.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Cães , Ensaio de Imunoadsorção Enzimática , Feminino , Hemaglutininas/análise , Hemaglutininas/imunologia , Pulmão/patologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Infecções por Orthomyxoviridae/imunologia , Polissorbatos , RNA Viral/genética , RNA Viral/isolamento & purificação , RNA Viral/metabolismo , Esqualeno/imunologia
20.
Mol Med Rep ; 17(5): 6245-6252, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29512744

RESUMO

The primary objective of the treatment of malignant ascites in advanced stages is to alleviate symptoms using procedures such as diuresis, paracentesis of subretinal fluid and vena cava anastomosis. The effectiveness of systemic or intraperitoneal chemotherapy treatment is limited, and more efficacious therapies are required. The authors of the present study demonstrated that an antimicrobial peptide, cecropinXJ, isolated from the larvae of Bombyx mori, selectively inhibits the proliferation of gastric cancer cells. However, the effects of antibacterial peptides on gastric ascites tumor remains unclear. In the present study, the therapeutic effects of cecropinXJ were investigated in mice bearing malignant ascites. Compared with bovine serum albumin treatment, cecropinXJ and doxorubicin (Dox) significantly inhibited the formation and growth of malignant ascites, and prolonged the survival time of ascites tumor­bearing mice. In addition, cecropinXJ treatment normalized the hematological and biochemical phenotypes, induced tumor cell apoptosis in ascites and improved the survival of mice bearing malignant ascites when compared with Dox treatment. These results suggested that cecropinXJ might be a promising therapeutic candidate for the treatment of gastric cancer­associated ascites.


Assuntos
Ascite/tratamento farmacológico , Cecropinas/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Animais , Ascite/metabolismo , Ascite/patologia , Linhagem Celular Tumoral , Doxiciclina/farmacologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
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