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1.
Clin Lab ; 67(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33616342

RESUMO

BACKGROUND: Rapid and accurate diagnosis of HIV-positive patients with Talaromyces marneffei (T. marneffei) infections remains challenging. A 60-year-old woman came to our inpatient department presenting with hematuria, abdominal pain, and diarrhea for one week. The patient had a past medical history of Acquired Immune Deficiency Syndrome (AIDS). The patient's stool was watery and the color of soy sauce. The patient was without fever, cough, and skin lesions. METHODS: The blood routine was performed with a Mindray BC-6900 hematology analyzer. RESULTS: Blood routine showed leukocytosis with neutrophilia and basophils and the WBC/DIFF scattergram showed a cluster of neutrophils connected with a monocyte and lymphocyte cluster and an additional cluster of immature granulocytes and heterotypic lymphocytes or primitive cells. Surprisingly, the peripheral blood film evaluation revealed small round-to-ovoid yeast cells within the cytoplasm of neutrophils. A T. marneffei infection was suspected and anti-fungal therapy was initiated. The patient's diarrhea improved after treatment with amphotericin B for two days. A second blood routine showed a normal number of leukocytes and basophils and a diminished cluster of immature granulocytes and heterotypic lymphocytes or primitive cells. After one week, blood cultures had grown T. marneffei. CONCLUSIONS: The WBC/DIFF scattergram obtained from a Mindray BC-6900 analyzer provided significant hints to enhance diagnosis of T. marneffei when combined with results of a peripheral blood smear.

2.
Dev Comp Immunol ; 115: 103903, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33098855

RESUMO

Peptidoglycan recognition proteins (PGRPs) are the most important pattern recognition receptors (PRRs) in insects. PGRPs can recognize pathogenic microorganism peptidoglycans (PGs) and play an important role in innate immunity. Twelve PGRPs have been identified in silkworms. However, the specific roles played by these PGPRs in the silkworm innate immune system have not been elucidated to date. In this study, we systematically investigated the biological functions of BmPGRP-S1 in silkworms. We observed that BmPGRP-S1 was highly expressed in silkworm immune-related organs and was upregulated in response to bacterial challenges. Furthermore, we determined that BmPGRP-S1 can bind to bacteria or PGs and activate antimicrobial peptide (AMP) expression. Inhibition of the expression of BmPGRP-S1 by siRNA reduced AMP gene expression in silkworms. Further experiments demonstrated that BmPGRP-S1 is involved in IMD pathway activation to induce AMP expression. Taken together, these results demonstrate that BmPGRP-S1 serves as a receptor to activate AMP gene expression through the IMD pathway to address bacterial challenges.

3.
Lancet Infect Dis ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217362

RESUMO

BACKGROUND: With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity. METHODS: In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18-59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac [3 µg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc [6 µg per 0·5 mL of aluminium hydroxide diluent per dse]). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with ClinicalTrials.gov, NCT04352608, and is closed to accrual. FINDINGS: Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 µg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 µg group, four (17%) of 24 in the 6 µg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 µg group, 12 (50%) of 24 in the 6 µg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 µg group, 19 (79%) of 24 in the 6 µg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 µg group, 42 (35%) of 120 in the 6 µg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 µg group, 23 (19%) of 120 in the 6 µg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 µg group, 117 (98%) of 119 in the 6 µg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 µg group, 118 (100%) of 118 in the 6 µg group, and none (0%) of 59 in the placebo group. INTERPRETATION: Taking safety, immunogenicity, and production capacity into account, the 3 µg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials. FUNDING: Chinese National Key Research and Development Program and Beijing Science and Technology Program.

4.
J Proteome Res ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175548

RESUMO

Lipids have been recently proposed as key molecules for virus entry and egress, and lipid biosynthesis and signaling were reported necessary for some viruses during replication and infection. The silkworm Bombyx mori is an important economic insect and a model organism, but its lipid profiles have not been systematically investigated. Most silkworm strains are susceptible to the B. mori nuclear polyhedrovirus (BmNPV), a baculovirus that causes serious loss to the sericulture industry. Previously, our lab has screened a natural mutant of B. mori that is highly resistant to BmNPV. In this study, a comprehensive lipidomic analysis by ultrahigh pressure liquid chromatography-mass spectrometry (UPLC-MS) was carried out on the BmNPV-susceptible strain 306 and resistant strain NB (data deposited in MetaboLight MTBLS2142). Comparisons of the lipid profiles between the two strains reveal that phosphosphingolipids, diacylglycerolipids, ceramides, and quinones were present at notably higher levels in the susceptible strain, while lysophosphocholines were found at a higher level in the resistant strain. BmNPV administration changed the lipid profiles in both strains, revealing key lipids involved in virus infection and immune response. Some key enzymes in the lipid biosynthesis pathway were analyzed for their activities in the two silkworm strains and their virus-administered counterparts, underlining the relation among lipid biosynthesis, viral resistance, and immune response in the host.

5.
Sci Rep ; 10(1): 19978, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203893

RESUMO

Pigeons, as the only altricial birds in poultry, are the primary Trichomonas gallinae (T. gallinae) host. To study the effects of T. gallinae infection on gut microbiota, we compared the microbiota diversity and composition in gastrointestinal (GI) tracts of pigeons at the age of 14 and 21 day with different degrees of T. gallinae infection. Thirty-six nestling pigeons were divided into three groups: the healthy group, low-grade and high-grade trichomonosis group. Then, the crop, small intestine and rectum contents were obtained for sequencing of the 16S rRNA gene V3-V4 hypervariable region. The results showed that the microbiota diversity was higher in crop than in small intestine and rectum, and the abundance of Lactobacillus genus was dominant in small intestine and rectum of healthy pigeons at 21 days. T. gallinae infection decreased the microbiota richness in crop at 14 days. The abundance of the Firmicutes phylum and Lactobacillus genus in small intestine of birds at 21 days were decreased by infection, however the abundances of Proteobacteria phylum and Enterococcus, Atopobium, Roseburia, Aeriscardovia and Peptostreptococcus genus increased. The above results indicated that crop had the highest microbiota diversity among GI tract of pigeons, and the gut microbiota diversity and composition of pigeon squabs were altered by T. gallinae infection.

6.
J Food Biochem ; : e13540, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33103256

RESUMO

The antioxidant and antidiabetic activities of vanadium-binding protein (VBP) and trifuhalol A, alone or combined, were investigated. Both VBP and trifuhalol A showed potent radical scavenging activity (RSA) on 2,2'-azinobis (3-ethylbenzothiazoline)-6-sulfonic acid (ABTS), hydrogen peroxide, and ferric-reducing antioxidant power. Their combination at a concentration of 100 µg/ml VBP and 40 µg/ml trifuhalol A exhibited more than 99% RSA against ABTS. Additionally, VBP and trifuhalol A, alone or combined, displayed potential antidiabetic activities against Saccharomyces cerevisiae α-glucosidase. The highest inhibition of 70.26% against S. cerevisiae α-glucosidase was observed in the case of the combination of 250 µg/ml VBP and 1.75 µg/ml trifuhalol A. Kinetics study revealed that VBP and trifuhalol A were noncompetitive inhibition type against S. cerevisiae α-glucosidase, while VBP and trifuhalol A combined treatment was a mixed inhibition type against S. cerevisiae α-glucosidase. These results indicated that VBP and trifuhalol A, alone or combined, had high free radical scavenging activity and inhibitory activity against S. cerevisiae a-glucosidase, suggesting that VBP and trifuhalol A could be used as candidates for the development of natural antidiabetic drugs or functional food. PRACTICAL APPLICATIONS: The present study showed that VBP and trifuhalol A, alone or combined, had potential antioxidant and antidiabetic activities, suggesting that VBP and trifuhalol A could be developed to a novel nutraceutical or natural antidiabetic drugs in the management of obesity or diabetes. This finding will be beneficial for all peoples who are directly or indirectly associated with obesity or diabetes.

7.
MycoKeys ; 73: 133-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117082

RESUMO

The genus Conidiobolus Bref. is widely distributed and the Conidiobolus sensu lato contained three other genera, Capillidium, Microconidiobolus and Neoconidiobolus. A molecular phylogeny based on the nuclear large subunit of rDNA (nucLSU), the mitochondrial small subunit of rDNA (mtSSU) and the translation elongation factor 1-alpha gene (TEF1) revealed three novel species within the clade of Conidiobolus s.s., i.e. C. bifurcatus sp. nov., C. taihushanensis sp. nov. and C. variabilis sp. nov. These three species were isolated from plant debris in eastern China. Morphologically, C. bifurcatus sp. nov. is characterised by its secondary conidiophores often branched at the tip to form two short stipes each bearing a secondary conidium. C. taihushanensis sp. nov. is different from the others in its straight apical mycelia and the production of 2-5 conidia. C. variabilis sp. nov. is distinctive because of its various shapes of primary conidia. All these three new taxa are illustrated herein with an update key to the species of the genus Conidiobolus s.s.

8.
Environ Res ; 188: 109802, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32592940

RESUMO

VOCs emissions from motor vehicles have become a main source of air pollution in many cities. However, the characteristics of VOCs emissions have not been fully elucidated. Ten representative vehicles were selected in Wuhan, China, and the VOCs emitted by these vehicles under actual working conditions were collected and analyzed through on-road tests. Results showed that the average concentrations of total VOCs emitted by gasoline and diesel vehicles were 5.9 ± 2.4 mg/m3 and 6.8 ± 3.0 mg/m3, while the average emission factors were 5.3 ± 2.2 mg/km and 33.9 ± 22.7 mg/km, respectively. The five compounds emitted at the highest levels by gasoline and diesel vehicles were hexanal, acetone, toluene, p-xylene and iso-pentane. Emission concentration of diesel vehicles was slightly higher than that of gasoline vehicles. Emission factor of diesel vehicles was much higher, because they consumed more fuel and produced more power than gasoline vehicles. The average concentrations of total VOCs emitted by China III, IV and V vehicles were 8.4 ± 1.4 mg/m3, 5.8 ± 3.4 mg/m3 and 5.3 ± 1.9 mg/m3, and their average emission factors were 21.7 ± 18.6 mg/km, 19.4 ± 28.9 mg/km and 9.1 ± 7.2 mg/km, respectively. Vehicle emissions decreased obviously as the emission standards increased. The average concentrations of total VOCs emitted under low-speed and high-speed conditions were 9.4 ± 3.5 mg/m3 and 5.5 ± 1.8 mg/m3. Concentrations of acetone, hexanal, toluene and p-xylene were the highest four VOCs under both conditions. The average emission factor of VOCs under high-speed conditions (24.0 ± 13.6 mg/km) was substantially lower than under low-speed conditions (54.0 ± 41.5 mg/km). Thus, tightening emission standards and reducing traffic congestion would help reduce VOCs emissions.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Cidades , Monitoramento Ambiental , Gasolina/análise , Veículos Automotores , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise
9.
Sci Total Environ ; 739: 139791, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32535462

RESUMO

The effect of the nonsphericity of mineral dust aerosols on its deposition and transport was investigated based on model simulation for a typical dust event over northern China from April 6 to 12, 2018. The settling velocity related to morphological change in dust size was considered in Nested Air Quality Prediction Modeling System (NAQPMS) to simulate the dust spatial distribution. Comparison of these results with observations showed that the model reproduced the temporal variability in the mass concentration of particles along the dust plume pathway. The most frequently reported aspect ratio (λ) was 1.7 ± 0.2 for Asian dust aerosols. Changing the nonsphericity of the particle from typical prolate ellipsoids (λ = 1.7) to spherical ellipsoids (λ = 1) caused an ~3% decrease in the surface dust concentration on average. For particles with diameters >5 µm, nonsphericity caused a change in the surface dust concentration up to 10%, especially at the periphery of the dust source region. The overall effects on the fine dust (<2.5 µm) were not significant. A sensitivity study using a more extreme nonspherical shape (λ = 2) showed that the differences in PM10 concentration were evident, and the surface dust concentration increased by 15 ± 5% as a result of an ~10% decrease in settling velocity. These results confirmed that the effect of the variability in the nonsphericity of Asian dust particles on their regional transport highly depended on synoptical and pollution conditions, and the adoption of a deposition value that changes over time due to this morphological variability could improve the performance of dust modeling and the assessment of climate effects on a global scale, especially for transboundary processes.

10.
J Proteomics ; 222: 103802, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32360640

RESUMO

The biological functions of protein glycosylation have been increasingly recognized but not yet been very well understood, especially in lower organisms. Silkworm as a model lepidopteran insect and important economic insect, has been widely studied in life science, however, the current knowledge on the glycosylation status of its proteome is not satisfactory, and little is known about how pathogenic infections could affect the glycosylation status. This study performed large scale glycosite mapping for the silkworm Bombyx mori P50 strain, and quantitatively compared with that infected with the Bombyx mori cytoplasmic polyhedrosis virus (BmCPV). Some 400 glycoproteins were mapped in the silkworm, including N- and O-glycoproteins. Upon virus infection, the glycosylation levels of 41 N-glycopeptides were significantly changed, some of them belonging to transmembrane glycoproteins. The O-glycosylation profiles were also affected. In addition, 4 BmCPV-encoded viral proteins were found to be glycosylated for the first time, including polyhedrin, P101, VP3, and the NS protein. This study drafted a silkworm protein glycosylation map and underlined the potential impact of virus infection on glycosylation. SIGNIFICANCE: This study reveals the characteristics of the glycoproteome in the silkworm strain P50, and quantitatively compared to that infected by the virus BmCPV, which underlines the impact of virus infection on the alteration of protein glycosylation in invertebrate species. Our findings add to the knowledge of the post translational modifications of this model organism, and also uncovered for the first time the glycosylation status of the viral proteins expressed by BmCPV.

11.
Biosci Rep ; 40(6)2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32436936

RESUMO

The present study was designed to investigate the role of amylin, H2S, and connexin 43 in vascular dysfunction and enhanced ischemia-reperfusion (I/R)-induced myocardial injury in diabetic rats. A single dose of streptozotocin (65 mg/kg) was employed to induce diabetes mellitus. After 8 weeks, there was a significant decrease in the plasma levels of amylin, an increase in I/R injury to isolated hearts (increase in CK-MB and cardiac troponin release) on the Langendorff apparatus. Moreover, there was a significant impairment in vascular endothelium function as assessed by quantifying acetylcholine-induced relaxation in norepinephrine-precontracted mesenteric arteries. There was also a marked decrease in the expression of H2S and connexin 43 in the hearts following I/R injury in diabetic rats. Treatment with amylin agonist, pramlintide (100 and 200 µg/kg), and H2S donor, NaHS (10 and 20 µmol/kg) for 2 weeks improved the vascular endothelium function, abolished enhanced myocardial injury and restored the levels of H2S along with connexin 43 in diabetic animals. However, pramlintide and NaHS failed to produce these effects the presence of gap junction blocker, carbenoxolone (20 and 40 mg/kg). Carbenoxolone also abolished the myocardial levels of connexin 43 without affecting the plasma levels of amylin and myocardial levels of H2S. The decrease in the amylin levels with a consequent reduction in H2S and connexin 43 may contribute to inducing vascular dysfunction and enhancing I/R-induced myocardial injury in diabetic rats.

12.
Arch Biochem Biophys ; 686: 108364, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32315653

RESUMO

Fucoxanthin (Fx), a major carotenoid found in brown seaweed, is known to show a unique and wide variety of biological activities. Upon absorption, Fx is metabolized to fucoxanthinol and amarouciaxanthin, and these metabolites mainly accumulate in visceral white adipose tissue (WAT). As seen in other carotenoids, Fx can quench singlet oxygen and scavenge a wide range of free radicals. The antioxidant activity is related to the neuroprotective, photoprotective, and hepatoprotective effects of Fx. Fx is also reported to show anti-cancer activity through the regulation of several biomolecules and signaling pathways that are involved in either cell cycle arrest, apoptosis, or metastasis suppression. Among the biological activities of Fx, anti-obesity is the most well-studied and most promising effect. This effect is primarily based on the upregulation of thermogenesis by uncoupling protein 1 expression and the increase in the metabolic rate induced by mitochondrial activation. In addition, Fx shows anti-diabetic effects by improving insulin resistance and promoting glucose utilization in skeletal muscle.


Assuntos
Suplementos Nutricionais/análise , Alga Marinha/química , Xantofilas/química , Xantofilas/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Descoberta de Drogas , Radicais Livres/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Resistência à Insulina , Fígado/metabolismo , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Depuradores/metabolismo , Oxigênio Singlete/metabolismo , Proteína Desacopladora 1/química , Proteína Desacopladora 1/metabolismo , Xantofilas/efeitos adversos , beta Caroteno/análogos & derivados , beta Caroteno/química
13.
MycoKeys ; 66: 55-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273794

RESUMO

The genus Conidiobolus is an important group in entomophthoroid fungi and is considered to be polyphyletic in recent molecular phylogenies. To re-evaluate and delimit this genus, multi-locus phylogenetic analyses were performed using the large and small subunits of nuclear ribosomal DNA (nucLSU and nucSSU), the small subunit of the mitochondrial ribosomal DNA (mtSSU) and the translation elongation factor 1-alpha (EF-1α). The results indicated that the Conidiobolus is not monophyletic, being grouped into a paraphyletic grade with four clades. Consequently, the well-known Conidiobolus is revised and three new genera Capillidium, Microconidiobolus and Neoconidiobolus are proposed along with one new record and 22 new combinations. In addition, the genus Basidiobolus is found to be basal to the other entomophthoroid taxa and the genus Batkoa locates in the Entomophthoraceae clade.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32231640

RESUMO

Background: The effect of testosterone supplementation in patients with chronic heart failure (CHF) remains uncertain. Methods: A meta-analysis of randomized controlled trials (RCTs) was performed. RCTs that evaluate the chronic effect of testosterone supplementation on exercise capacity and cardiac function in CHF were identified via searching of PubMed, Embase, and the Cochrane's Library databases. Heterogeneity was evaluated by the Cochrane's Q test and I 2 statistics. A fixed-effect model was used if the heterogeneity was not significant (I 2 < 50%); otherwise, a random-effect model was applied. Results: Eight studies including 170 patients in the testosterone supplementation group and 162 in the control group were included. Overall, testosterone supplementation was not associated with an improved exercise capacity (walking test: standardized mean difference [SMD] = 0.36, p = 0.07). Sensitivity analyses limited to male patients showed similar results (SMD = 0.21, p = 0.15), and subgroup analyses also showed similar results in male HF patients with baseline total testosterone (TT) ≥ or < 10 nmol/L. However, patients with TT at endpoint ≥ 25 nmol/L was associated with improved exercise capacity (SMD = 1.12, p = 0.02), but not for those with TT at endpoint < 25 nmol/L (SMD = 0.24, p = 0.12). In addition, VO2max (weight mean difference [WMD] = 0.85, p = 0.43), the functional classification (the New York Heart Association classification: WMD = -0.08, p = 0.16) and quality of life (Minnesota Living with Heart Failure [MLHF] questionnaire: WMD = -6.03, p = 0.12) were not significantly affected. Moreover, testosterone supplementation did not significantly affect left ventricular ejection fraction (WMD: -1.52%, p = 0.37), serum B-type natriuretic peptide (SMD: -0.19, p = 0.23), or a composite outcome of death or HF hospitalization (risk ratio [RR]: 1.02, p = 0.96). Although testosterone supplementation increased systolic blood pressure (BP) in CHF patients (WMD: 5.68 mmHg, p < 0.001), diastolic BP or heart rate was not significantly changed as compared to control. Conclusions: Testosterone supplementation within a physiological range is not associated with significantly improved exercise capacity, cardiac function, quality of life, or clinical outcome in CHF patients.

15.
J Cancer ; 11(9): 2580-2592, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32201528

RESUMO

Tumor associated neutrophils (TANs) play important roles in the progress of CRC. Since tumor microenvironments could influence the phenotypes of TANs, altering the tumor microenvironment to polarize the phenotype of TANs may be a new strategy for tumor treatment. This study aims to investigate the effect of anti-TGF-ß on the polarization of TANs from a pro-tumor phenotype towards an anti-tumor phenotype in CRC. In this work, CRC patients had more infiltration of TANs and higher expression of TGF-ß in CRC tissue when compared with the controls. In vitro, SW480 cells were co-cultured with primed neutrophils, which simulated the TANs in the tumor microenvironment, and TGF-ß was blocked by anti-TGF-ß (1D11) in order to polarize TANs. Anti-TGF-ß treatment increased the cytotoxicity of TANs and decreased the metastatic chemoattractants secreted by TANs, and ultimately increased the apoptosis of CRC cells significantly while remarkably suppressing the migration of tumor cells. The changes of signaling pathways in the TANs and tumor cells were explored. The results showed that anti-TGF-ß attenuated CRC may be partly mediated by suppression of PI3K/AKT signaling pathways in TANs and partly mediated by suppression of TGF-ß/Smad signaling pathways in tumor cells. Furthermore, the tumor in the mice treated with 1D11 was obviously smaller and had reverse tumorigenesis compared with the controls, while neutrophil depletion reduced the anti-tumor effect of 1D11. Our data suggest that anti-TGF-ß attenuates tumor growth via the polarization of TANs to an anti-tumor phenotype in CRC, which provides new strategies for CRC treatment.

16.
Z Naturforsch C J Biosci ; 75(1-2): 13-21, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31603862

RESUMO

Peptidoglycan recognition proteins (PGRPs) are pattern recognition receptors that can recognize bacterial peptidoglycans and trigger the innate immune response of insects. Here, we identified and characterized a novel short-type Bombyx mori peptidoglycan recognition proteins short-4 (BmPGRP-S4) in a lepidopteran insect, Bombyx mori. BmPGRP-S4 exhibited a cDNA sequence length of 600 bp, encoding 199 aa with a protein molecular weight of 22 kDa. Multiple sequence alignment revealed that BmPGRP-S4 contains a conserved PGRP domain. Quantitative real-time polymerase chain reaction analysis showed that BmPGRP-S4 is highly expressed in the early developmental stages of silkworm larvae and presents tissue-specific expression in hemocytes. Interestingly, BmPGRP-S4 expression is significantly induced by bacterial infection in the midgut, fat body, and hemocytes. Furthermore, a dual luciferase reporter gene assay revealed that BmPGRP-S4 can activate the expression of the antimicrobial peptide genes lebocin, moricin, cecropin D, cecropin B, and attacin. Taken together, these results suggest that BmPGRP-S4 plays an important role in the innate immune response of silkworms.


Assuntos
Bombyx/genética , Proteínas de Transporte/genética , Imunidade Inata/genética , Sequência de Aminoácidos/genética , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Proteínas de Transporte/química , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/imunologia , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Proteínas de Insetos/genética , Larva/química , Larva/genética , Alinhamento de Sequência
17.
Life Sci ; 254: 117041, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31715188

RESUMO

AIM: The present study explored the role and possible interrelationship between orexin B-sirtuin 1-HIF-1α signaling pathways in diabetes-mellitus induced vascular dysfunction and enhancement in myocardial injury. MATERIAL AND METHODS: Streptozotocin (60 mg/kg) was employed to induce diabetes mellitus in male Wistar albino rats, which were kept for eight weeks. The vascular function was noted by assessing acetylcholine-induced relaxation in norepinephrine precontracted mesenteric arteries. The hearts were subjected to ischemia-reperfusion injury on the Langendorff apparatus. Myocardial injury was assessed by noting the release of CK-MB, cardiac troponin and measuring myocardial infarction. The levels of orexin B, sirtuin 1 and HIF-1α were measured. YNT-185 (orexin B type 2 receptor agonist), STR2104 (sirtuin 1 agonist) and EX527 (sirtuin 1 antagonist) were employed as pharmacological tools. RESULTS: Diabetes led to significant development of vascular dysfunction and enhanced ischemia-reperfusion injury in isolated hearts. There was a significant decrease in the levels of orexin B, sirtuin 1 and HIF-1α in diabetic animals. Treatment with YNT-185 and/or STR2104 significantly attenuated the diabetes-induced increase in myocardial injury and vascular dysfunction. Co-administration of EX527 abolished the effects of YNT-185 suggesting orexin B-mediated effects may be through activation of sirtuin 1. Moreover, YNT-185-induced increase in the expression of sirtuin 1 and HIF-1α was also abolished in the presence of EX527. CONCLUSION: Diabetes-induced significant decline in orexin B levels in the plasma along with a decrease in the expression of sirtuin 1 and HIF-1α in the heart following ischemia-reperfusion injury may possibly contribute in exacerbating the myocardial injury and vascular dysfunction.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Endotélio Vascular/fisiopatologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Infarto do Miocárdio/metabolismo , Orexinas/metabolismo , Sirtuína 1/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Masculino , Infarto do Miocárdio/complicações , Orexinas/sangue , Ratos , Ratos Wistar
18.
J Invertebr Pathol ; 167: 107250, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31541622

RESUMO

Protein glycosylation plays important roles in protein structure, function, and immune recognition, among many other activities. One of the major roles of glycans and glycoconjugates on the cell surface is acting as the receptor for outside pathogens such as viruses. During the initial stage of viral replication, viruses interact with cell membrane receptors, which are in many cases glycoproteins. Identifying such glycoproteins is essential to understanding the mechanisms of viral infection, as well as developing antiviral strategies. Silkworm is an important economic insect as well as a model organism for molecular biology, yet current knowledge on its glycoproteome is far from complete due to both analytical challenges and perceived lack of importance. In this study, we performed a large-scale glycoproteomic survey for two silkworm Bombyx mori strains 306 and NB, which are susceptible and resistant to the baculovirus Bombyx mori nucleopolyhedrovirus (BmNPV), respectively. More than 400 silkworm N- and O- glycoproteins were identified with high confidence, demonstrating that this organism employs extensive glycosylation. We mapped some glycoproteins only to the BmNPV susceptible or resistant strain, underlining the potential relationship between glycosylation and viral susceptibility. We predicted O-glycoproteins and O-glycan compositions for the first time for this organism. The variations in glycan site occupancy, as well as glycan diversity between the two silkworm strains, provide an insight into role of glycosylation in viral recognition and infection processes.


Assuntos
Bombyx/virologia , Glicoproteínas de Membrana/metabolismo , Nucleopoliedrovírus/patogenicidade , Animais , Bombyx/metabolismo , Suscetibilidade a Doenças , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/virologia , Glicoproteínas/metabolismo , Glicosilação , Interações entre Hospedeiro e Microrganismos , Polissacarídeos/metabolismo , Viroses , Internalização do Vírus
19.
Expert Opin Ther Targets ; 23(9): 805-817, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31385548

RESUMO

Background: Pterygium, a common eye disease with high postoperative recurrence, lacks effective therapeutic strategies. Therefore, it's urgent to identify specific targets to develop rationally targeted molecular drugs for the pterygial therapy. Methods: The cell proliferation and motility were studied in both the primary human pterygial fibroblasts (hPFs) and an ex vivo pterygium model. hPFs transfected with the pCMV3-PDGFRB plasmid, PDGFRB siRNA and CRISPR/Cas9 system were used to determine the role of PDGFR-ß in pterygial fibroblasts functions. Western blotting, immunohistochemistry and immunofluorescence were performed to evaluate the expression of the key proteins. Results: PDGFR-ß expression in the pterygial stroma and primary hPFs was significantly higher than that in the conjunctiva and human conjunctival fibroblasts. PDGF-BB promoted the proliferation, migration and invasion of hPFs, which can be significantly suppressed by sunitinib via inhibition of the PDGFR-ß/extracellular signal-regulated kinase (ERK) pathway. In the ex vivo model, the knockout of PDGFRB and sunitinib treatment blocked the proliferation and motility of fibroblasts in the pterygial stroma via the suppression of PDGFR-ß/ERK pathway. Conclusion: This study demonstrates that PDGFR-ß may be a potential therapeutic target for pterygium, and inhibition of PDGFR-ß by sunitinib is a promising and effective approach for pterygium treatment.


Assuntos
Inibidores de Proteínas Quinases/farmacologia , Pterígio/tratamento farmacológico , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Sunitinibe/farmacologia , Proteína 9 Associada à CRISPR/genética , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Técnicas de Inativação de Genes , Humanos , Terapia de Alvo Molecular , Pterígio/patologia
20.
Braz J Med Biol Res ; 52(7): e8416, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314851

RESUMO

Studies regarding the prognostic value of circulating adiponectin level in patients with heart failure are conflicting. The aim of this meta-analysis was to evaluate the association between elevated circulating adiponectin level and adverse outcomes in patients with heart failure. We searched PubMed and Embase databases from their inception to June 2018. Original observational studies that investigated the prognostic value of adiponectin in heart failure patients and reported all-cause mortality or combined endpoints of death/readmission as outcome measure were included. Pooled risk ratio (RR) with 95% confidence intervals (CI) were estimated by higher versus lower circulating adiponectin level. A total of 7 studies involving 862 heart failure patients were identified. Meta-analysis showed that heart failure patients with higher adiponectin level had significantly increased risk of all-cause mortality (RR 2.05; 95%CI 1.22-3.43) after adjustment for potential confounders. In addition, higher adiponectin level was associated with an increased risk of the combined endpoints of death/readmission (RR 2.22; 95%CI 1.38-3.57). Elevated baseline circulating adiponectin level is possibly associated with an increased risk of all-cause mortality and the combined endpoints of death/readmission in patients with heart failure. Determination of circulating adiponectin level has potential to improve risk stratification in heart failure patients.


Assuntos
Adiponectina/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Biomarcadores/sangue , Humanos , Prognóstico , Fatores de Risco
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