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1.
BMC Vet Res ; 19(1): 255, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38053138

RESUMEN

BACKGROUND: Multidrug resistance in Enterobacteriaceae including resistance to quinolones is rising worldwide. The development of resistance may lead to the emergence of new transmission mechanisms. In this study, the collection of different E. coli was performed from animals and subjected to subsequent procedures including pulsed-field gel electrophoresis, micro-broth dilution method, polymerase chain reaction. Whole genome sequencing of E. coli C3 was performed to detect the affinity, antimicrobial resistance and major carriers of the isolates. RESULTS: A total of 66 E. coli were isolated and their antibiotic resistance genes, frequency of horizontal transfer and genetic environment of E. coli C3 were determined. The results showed there were both different and same types in PFGE typing, indicating clonal transmission of E. coli among different animals. The detection of antimicrobial resistance and major antibiotic resistance genes and the plasmid transfer results showed that strains from different sources had high levels of resistance to commonly used clinical antibiotics and could be spread horizontally. Whole-genome sequencing discovered a novel ICE mobile element. CONCLUSION: In summary, the antimicrobial resistance of E. coli in northeast China is a serious issue and there is a risk of antimicrobial resistance transmission. Meanwhile, a novel ICE mobile element appeared in the process of antimicrobial resistance formation.


Asunto(s)
Infecciones por Escherichia coli , Escherichia coli , Animales , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Infecciones por Escherichia coli/veterinaria , Enterobacteriaceae , China , Pruebas de Sensibilidad Microbiana/veterinaria , Plásmidos , Electroforesis en Gel de Campo Pulsado/veterinaria , beta-Lactamasas/genética
2.
Postgrad Med ; 135(8): 831-841, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38032178

RESUMEN

OBJECTIVE: In this study, we evaluated the clinical utility of tracheal aspirates α-amylase (AM), pepsin, and lipid-laden macrophage index (LLMI) in the early diagnosis of ventilator-associated pneumonia (VAP) in elderly patients on mechanical ventilation. METHODS: Within 96 hours of tracheal intubation, tracheal aspirate specimens were collected from elderly patients on mechanical ventilation; AM, pepsin, and LLMI were detected, and we analyzed the potential of each index individually and in combination in diagnosing VAP. RESULTS: Patients with VAP had significantly higher levels of AM, pepsin, and LLMI compared to those without VAP (P < 0.001), and there was a positive correlation between the number of pre-intubation risk factors of aspiration and the detection value of each index in patients with VAP (P < 0.001). The area under a receiver operating characteristic (ROC) curve (AUC) of AM, pepsin, and LLMI in diagnosis of VAP were 0.821 (95% CI:0.713-0.904), 0.802 (95% CI:0.693-0.892), and 0.621 (95% CI:0.583-0.824), the sensitivities were 0.8815, 0.7632, and 0.6973, the specificities were 0.8495, 0.8602, and 0.6291, and the cutoff values were 4,321.5 U/L, 126.61 ng/ml, and 173.5, respectively. The AUC for the combination of indexes in diagnosing VAP was 0.905 (95% CI:0.812-0.934), and the sensitivity and specificity were 0.9211 and 0.9332, respectively. In the tracheal aspirate specimens, the detection rate of AM ≥ cutoff was the highest, while it was the lowest for LLMI (P < 0.001). The detection rates of AM ≥ cutoff and pepsin ≥ cutoff were higher within 48 hours after intubation than within 48-96 hours after intubation (P < 0.001). In contrast, the detection rate of LLMI ≥ cutoff was higher within 48-96 hours after intubation than within 48 hours after intubation (P < 0.001). The risk factors for VAP identified using logistic multivariate analysis included pre-intubation aspiration risk factors (≥3), MDR bacteria growth in tracheal aspirates, and tracheal aspirate AM ≥ 4,321.5 U/L, pepsin ≥ 126.61 ng/ml, and LLMI ≥ 173.5. CONCLUSION: The detection of AM, pepsin, and LLMI in tracheal aspirates has promising clinical utility as an early warning biomarker of VAP in elderly patients undergoing mechanical ventilation.


Asunto(s)
Neumonía Asociada al Ventilador , Respiración Artificial , Humanos , Anciano , Respiración Artificial/efectos adversos , Neumonía Asociada al Ventilador/etiología , Neumonía Asociada al Ventilador/microbiología , Pepsina A/análisis , Intubación Intratraqueal/efectos adversos , Biomarcadores/análisis , Unidades de Cuidados Intensivos
3.
Bioprocess Biosyst Eng ; 46(11): 1639-1650, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37733076

RESUMEN

With potent herbicidal activity, biocatalysis synthesis of L-glufosinate has drawn attention. In present research, NAP-Das2.3, a deacetylase capable of stereoselectively resolving N-acetyl-L-glufosinate to L-glufosinate mined from Arenimonas malthae, was heterologously expressed and characterized. In Escherichia coli, NAP-Das2.3 activity only reached 0.25 U/L due to the formation of inclusive bodies. Efficient soluble expression of NAP-Das2.3 was achieved in Pichia pastoris. In shake flask and 5 L bioreactor fermentation, NAP-Das2.3 activity by recombinant P. pastoris reached 107.39 U/L and 1287.52 U/L, respectively. The optimum temperature and pH for N-acetyl-glufosinate hydrolysis by NAP-Das2.3 were 45 °C and pH 8.0, respectively. The Km and Vmax of NAP-Das2.3 towards N-acetyl-glufosinate were 25.32 mM and 19.23 µmol mg-1 min-1, respectively. Within 90 min, 92.71% of L-enantiomer in 100 mM racemic N-acetyl-glufosinate was converted by NAP-Das2.3. L-glufosinate with high optical purity (e.e.P above 99.9%) was obtained. Therefore, the recombinant NAP-Das2.3 might be an alternative for L-glufosinate biosynthesis.


Asunto(s)
Reactores Biológicos , Pichia , Proteínas Recombinantes/química , Pichia/genética , Pichia/metabolismo , Fermentación
4.
Commun Chem ; 6(1): 176, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612464

RESUMEN

Bicyclic boronates play critical roles in the discovery of functional materials and antibacterial agents, especially against deadly bacterial pathogens. Their practical and convenient preparation is in high demand but with great challenge. Herein, we report an efficient strategy for the preparation of bicyclic boronates through metal-free heteroatom-directed alkenyl sp2-C‒H borylation. This synthetic approach exhibits good functional group compatibility, and the corresponding boronates bearing halides, aryls, acyclic and cyclic frameworks are obtained with high yields (43 examples, up to 95% yield). Furthermore, a gram-scale experiment is conducted, and downstream transformations of the bicyclic boronates are pursued to afford natural products, drug scaffolds, and chiral hemiboronic acid catalysts.

5.
J Colloid Interface Sci ; 636: 492-500, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36652824

RESUMEN

Exploring highly efficient electromagnetic interference (EMI) shielding filler is urgently desired for next-generation wireless communication and integrated electronics. In this regard, a series of heterogeneous MoO2/N-doped carbon (MoO2/NC) nanorods with tunable conductivity have been successfully synthesized by regulating the pyrolysis temperature within 600, 700 and 800 °C. Profiting from the rational design of heterointerface and low-dimensional structure, the MoO2/NC powder achieves stronger EMI shielding capacity with the incremental temperature. It is found that the MoO2/NC-800 nanorods exhibit the optimal average EMI shielding effectiveness (SE) of 57.2 dB at a thickness of ∼0.3 mm in the X band. Meanwhile, the corresponding shielding mechanisms of MoO2/NC nanorods are also elaborately explained. More interestingly, the increase of sintering temperature makes an obvious effect on absorption loss but has little influence on reflection loss, demonstrating that adjusting the pyrolysis temperature is an effective strategy to strengthen the electromagnetic energy dissipation.

6.
Pulm Circ ; 12(2): e12070, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35514783

RESUMEN

This study aims to determine the function of topotecan (TPT) in acute lung injury (ALI) induced by sepsis. The mouse sepsis model was constructed through cecal ligation and puncture (CLP). The ALI score and lung wet/dry (W/D) weight ratio were applied to evaluate the level of lung injury. Hematoxylin-eosin staining was used to examine the role of TPT in lung tissue in a CLP-induced ALI mouse model. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were used to detect the concentrations of inflammatory factors, such as interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α. Western blot was used to detect relevant protein levels in the nuclear factor-κB (NF-κB) pathway. Moreover, 10-day survival was recorded by constructing the CLP model. The results indicated that TPT could improve lung tissue damage in mice and could significantly reduce lung injury scores (p < 0.01) and the W/D ratio (p < 0.05). Treatment with ammonium pyrrolidinedithiocarbamate obtained the similar results with the TPT treatment. Both significantly reduced the inflammatory response in the lungs, including reducing the number of neutrophils and total cells in the bronchoalveolar lavage fluid (BALF), significantly reducing the total protein concentration of the BALF, and significantly inhibiting the activity of MPO. Both also inhibited inflammatory cytokine expression and the levels of NF-κB pathway proteins induced by sepsis. Furthermore, TPT significantly improved survival in sepsis. TPT improves ALI in the CLP model by inhibiting the NF-κB pathway, preventing fatal inflammation.

7.
Mol Cell Biochem ; 477(2): 385-393, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34757567

RESUMEN

Lung cancer is one of the most prevalent causes of morbidity and mortality in both men and women across the globe. The disease has a quiet phenotype at first, which leads to chronic tumor development. Non-small cell lung cancer (NSCLC) is the most common kind of lung cancer, accounting for 85 percent of all lung malignancies. Autophagy has been described as an intracellular "recycle bin" where damaged proteins and molecules are degraded. Autophagy regulation is mainly dependent on signaling pathways such as phosphoinositide 3-kinases (PI3K), AKT, and the mammalian target of rapamycin (mTOR). In the context of NSCLC, studies on these signaling pathways are inconsistent, but our literature review suggests that the inhibition of mTOR, PI3K/AKT, and epidermal growth factor receptor signaling pathways by different medications can active autophagy and inhibit NSCLC progression. In conclusion, signaling pathways related to autophagy are effective therapeutic approaches for the treatment of NSCLC.


Asunto(s)
Autofagia , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Transducción de Señal , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Proteínas de Neoplasias/genética
8.
BMC Pulm Med ; 21(1): 208, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34210314

RESUMEN

BACKGROUND: Molecular targeted therapy for non-small cell lung carcinoma (NSCLC) is restricted due to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This study evaluated the effects of dual targeting of MEK and PI3K in human EGFR-TKI resistant NSCLC cell lines. METHODS: EGFR-TKI resistant NSCLC cell lines H1975, H460, and A549, with different mutation and amplification status in EGFR, K-RAS, PIK3CA, and MET genes, were treated with a MEK162 (MEK inhibitor) and BKM120 (PI3K inhibitor) combination or a BIBW2992 (EGFR inhibitor) and ARQ197 (MET inhibitor) combination and assayed for cell proliferation, apoptosis, and cell cycle distribution. RESULTS: Dual targeting of MEK and PI3K efficiently inhibited the cell proliferation, induced apoptosis and the G0/G1 cell cycle, and decreased the phosphorylation of ERK1/2, AKT, S6, and 4E-BP1. H460 cells with K-RAS and PIK3CA mutation were most sensitive to MEK162 and BKM120 combinations. H1975 cells with EGFR and PIK3CA mutation and MET amplification were sensitive to BIBW2992 and ARQ197 combinations. CONCLUSION: Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics.


Asunto(s)
Afatinib/farmacología , Aminopiridinas/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/patología , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Morfolinas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Mutación , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Pirrolidinonas/farmacología , Quinolinas/farmacología
9.
Regen Biomater ; 8(1): rbaa056, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33732501

RESUMEN

Endoscopic submucosal dissection (ESD) is the standard treatment for early-stage gastric cancer, but the large post-operative ulcers caused by ESD often lead to serious side effects. Post-ESD mucosal repair materials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a polyurethane/small intestinal submucosa (PU/SIS) hydrogel and investigated its efficacy for accelerating ESD-induced ulcer healing in a canine model. PU/SIS hydrogel possessed great biocompatibility and distinctive pH-sensitive swelling properties and protected GES-1 cells from acid attack through forming a dense film in acidic conditions in vitro. Besides, PU/SIS gels present a strong bio-adhesion to gastric tissues under acidic conditions, thus ensuring the retention time of PU/SIS gels in vivo. In a canine model, PU/SIS hydrogel was easily delivered via endoscopy and adhered to the ulcer sites. PU/SIS hydrogel accelerated gastric ulcer healing at an early stage with more epithelium regeneration and slight inflammation. Our findings reveal PU/SIS hydrogel is a promising and attractive candidate for ESD-induced ulcer repair.

10.
Zhonghua Nan Ke Xue ; 26(10): 881-887, 2020 Nov.
Artículo en Chino | MEDLINE | ID: mdl-33382218

RESUMEN

OBJECTIVE: To investigate the relationship between the apparent diffusion coefficient (ADC) histogram parameters based on the whole tumor and the pathological grade and lymph node metastasis (LNM) of PCa. METHODS: This retrospective study included 82 cases of PCa confirmed pathologically and subjected to MRI preoperatively. We obtained a series of ADC histogram parameters, such as ADCmean, ADCmedian, ADC25%, ADC75%, entropy, and histogram width, by processing the ADC images via the Firevoxel Post-Processing and the SPSS24 software. We compared the parameters between the high-risk and low- or moderate-risk groups as well as between the LNM-positive and LNM-negative groups of the patients, and analyzed the diagnostic performance of the parameters with statistically significant differences. RESULTS: The high-risk group, compared with the low- or moderate-risk one, showed a significantly lower ADCmean (ï¼»590 ± 120ï¼½ vs ï¼»837 ± 142ï¼½ ×10-6 mm2/s, P < 0.01), ADCmedian (ï¼»560 ± 117ï¼½ vs ï¼»804 ± 139ï¼½ ×10-6 mm2/s, P < 0.01), ADC25% (ï¼»446.5 ± 98ï¼½ vs ï¼»717 ± 118ï¼½ ×10-6 mm2/, P < 0.01) and ADC75% (ï¼»667 ± 132ï¼½ vs ï¼»931 ± 167ï¼½ ×10-6 mm2/s, P < 0.01). The ADCmean manifested the highest diagnostic performance, with an AUC of 0.907, a sensitivity of 0.933 and a specificity of 0.796. No statistically significant difference was found between the high-risk and the low- or moderate-risk one in entropy (3.58 ± 0.39 vs 3.63 ± 0.42, P = 0.238) or the histogram width (ï¼»540 ± 73ï¼½ vs ï¼»520 ± 65ï¼½ ×10-6 mm2/s, P = 0.086). Both entropy and the histogram width were remarkably higher in the LNM-positive than in the LNM-negative group (3.95 ± 0.41 vs 3.12 ± 0.45, P < 0.01; ï¼»578 ± 59ï¼½ vs ï¼»455 ± 68ï¼½ ×10-6 mm2/s, P < 0.01), and the former had an even higher diagnostic performance, with an AUC of 0.836, a sensitivity of 0.887 and a specificity of 0.781. There were no statistically significant differences between the LNM-positive and LNM-negative groups in the ADCmean (ï¼»768 ± 135ï¼½ vs ï¼»790±128ï¼½ ×10-6 mm2/s, P = 0.402), ADCmedian (ï¼»759 ± 110ï¼½ vs ï¼»775 ± 121ï¼½ ×10-6 mm2/s, P = 0.225), ADC25% (ï¼»643 ± 91ï¼½ vs ï¼»657 ± 89ï¼½ ×10-6 mm2/s, P = 0.654) or ADC75% (ï¼»895 ± 127ï¼½ vs ï¼»872 ± 129ï¼½ ×10-6 mm2/s, P = 0.926). CONCLUSIONS: ADC histogram parameters are related to pathological grade and LNM of PCa, and the analysis of the ADC histogram based on the whole tumor has an important value for preoperative evaluation and prognostic estimation of the malignancy.


Asunto(s)
Imagen de Difusión por Resonancia Magnética , Metástasis Linfática , Neoplasias de la Próstata , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Estudios Retrospectivos
11.
PLoS Pathog ; 16(3): e1008405, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32176737

RESUMEN

Alcelaphine herpesvirus 1 (AlHV-1) is a gammaherpesvirus that is carried asymptomatically by wildebeest. Upon cross-species transmission to other ruminants, including domestic cattle, AlHV-1 induces malignant catarrhal fever (MCF), which is a fatal lymphoproliferative disease resulting from proliferation and uncontrolled activation of latently infected CD8+ T cells. Two laboratory strains of AlHV-1 are used commonly in research: C500, which is pathogenic, and WC11, which has been attenuated by long-term maintenance in cell culture. The published genome sequence of a WC11 seed stock from a German laboratory revealed the deletion of two major regions. The sequence of a WC11 seed stock used in our laboratory also bears these deletions and, in addition, the duplication of an internal sequence in the terminal region. The larger of the two deletions has resulted in the absence of gene A7 and a large portion of gene A8. These genes are positional orthologs of the Epstein-Barr virus genes encoding envelope glycoproteins gp42 and gp350, respectively, which are involved in viral propagation and switching of cell tropism. To investigate the degree to which the absence of A7 and A8 participates in WC11 attenuation, recombinant viruses lacking these individual functions were generated in C500. Using bovine nasal turbinate and embryonic lung cell lines, increased cell-free viral propagation and impaired syncytia formation were observed in the absence of A7, whereas cell-free viral spread was inhibited in the absence of A8. Therefore, A7 appears to be involved in cell-to-cell viral spread, and A8 in viral cell-free propagation. Finally, infection of rabbits with either mutant did not induce the signs of MCF or the expansion of infected CD8+ T cells. These results demonstrate that A7 and A8 are both essential for regulating viral spread and suggest that AlHV-1 requires both genes to efficiently spread in vivo and reach CD8+ T lymphocytes and induce MCF.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Gammaherpesvirinae/inmunología , Genes Virales/inmunología , Fiebre Catarral Maligna/inmunología , Proteínas del Envoltorio Viral/inmunología , Animales , Bovinos , Línea Celular , Gammaherpesvirinae/genética , Fiebre Catarral Maligna/genética , Conejos , Proteínas del Envoltorio Viral/genética
12.
Mol Immunol ; 114: 226-232, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31386979

RESUMEN

Foot and mouth disease virus (FMDV), a member of family Picornaviridae, belongs to the genus Aphthovirus, which causes foot and mouth disease (FMD), a highly transmissible disease that affects cloven-hoof animals. In spite of the fact that efficient vaccines are available, effective antiviral molecules for FMD are needed to reduce viral infection during early stages of infection. In this study, merimepodib was found to efficiently inhibit FMDV replication in a dose-dependent manner. The 50% inhibitory concentration (IC50) of merimepodib antiviral activity against two distinct FMDV strains (O/MYA98/BY/2010 and A/GD/MM/CHA/2013) was estimated to be 7.859 and 2.876 µM, respectively, while the 50% cytotoxic concentration (CC50) of merimepodib was found to be 47.74 µM. Furthermore, treatment with 30 µg merimepodib efficiently prolonged the survival time of suckling mice infected with FMDV. Taken together, these results suggested that merimepodib has the potential to be a novel antiviral agent against FMDV.


Asunto(s)
Antivirales/farmacología , Carbamatos/farmacología , Virus de la Fiebre Aftosa/efectos de los fármacos , Fiebre Aftosa/tratamiento farmacológico , Compuestos de Fenilurea/farmacología , Animales , Línea Celular , Ratones , Porcinos , Vacunas Virales/farmacología , Replicación Viral/efectos de los fármacos
13.
Microb Pathog ; 135: 103638, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31326561

RESUMEN

Recently, amiloride was shown to potently suppress Coxsackievirus B3 (CVB3) replication. In the current study, we investigated whether amiloride could also exhibit antiviral activity against foot-and-mouth disease virus (FMDV), which belongs to the same family (Picornaviridae) as CVB3. We found that amiloride exerted antiviral activity in a dose-dependent manner against two strains of FMDV in IBRS-2 cells, with slight cytotoxicity at 1000 µM. Besides, amiloride did not inhibit the attachment and entry of FMDV in IBRS-2 cells, but prevented early viral replication. These data implied that amiloride could be a promising candidate for further research as a potential antiviral drug against FMDV infection.


Asunto(s)
Amilorida/farmacología , Antivirales/farmacología , Virus de la Fiebre Aftosa/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Animales , Técnicas de Cultivo de Célula , Línea Celular , Supervivencia Celular , Replicación del ADN/efectos de los fármacos , Fiebre Aftosa/virología , Humanos , ARN Mensajero/metabolismo , Proteínas Virales
14.
Molecules ; 24(9)2019 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-31058822

RESUMEN

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which has significant economic consequences in affected countries. As the currently available vaccines against FMD provide no protection until 4-7 days post-vaccination, the only alternative method to control the spread of FMD virus (FMDV) during outbreaks is the application of antiviral agents. Hence, it is important to identify effective antiviral agents against FMDV infection. In this study, we found that mizoribine has potent antiviral activity against FMDV replication in IBRS-2 cells. A time-of-drug-addition assay demonstrated that mizoribine functions at the early stage of replication. Moreover, mizoribine also showed antiviral effect on FMDV in vivo. In summary, these results revealed that mizoribine could be a potential antiviral drug against FMDV.


Asunto(s)
Antivirales/administración & dosificación , Virus de la Fiebre Aftosa/fisiología , Fiebre Aftosa/tratamiento farmacológico , Ribonucleósidos/administración & dosificación , Animales , Antivirales/química , Antivirales/farmacología , Línea Celular , Brotes de Enfermedades , Fiebre Aftosa/epidemiología , Fiebre Aftosa/virología , Virus de la Fiebre Aftosa/efectos de los fármacos , Regulación Viral de la Expresión Génica/efectos de los fármacos , Ratones , Ribonucleósidos/química , Ribonucleósidos/farmacología , Porcinos , Proteínas Virales/metabolismo , Replicación Viral/efectos de los fármacos
15.
Biomed Pharmacother ; 116: 108982, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31146110

RESUMEN

Foot-and-mouth disease (FMD) is one of the most highly contagious animal disease that affects cloven-hoofed animals. However, the FMD vaccine does not provide effective protection until adaptive immune protection elicited by the vaccination occurs. Therefore, an alternative application of antiviral agents for inhibition of the FMD virus (FMDV) is needed. Here, we demonstrated that brequinar could exhibit antiviral activity in swine kidney cells (IBRS-2 cells) infected with two different FMDV serotypes. Subsequently, in vivo activity of brequinar was confirmed in a mouse model of infection. Specifically, brequinar at a concentration of 50 µg, provided 25% protection for 5 days following FMDV challenge. These results suggested that brequinar could be used as effective antiviral agent against FMD.


Asunto(s)
Antivirales/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Virus de la Fiebre Aftosa/fisiología , Fiebre Aftosa/tratamiento farmacológico , Fiebre Aftosa/virología , Animales , Antivirales/química , Antivirales/farmacología , Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular , Virus de la Fiebre Aftosa/efectos de los fármacos , Miocardio/patología , Porcinos , Uridina/farmacología
16.
J Med Virol ; 91(9): 1595-1601, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31032977

RESUMEN

Foot-and-mouth disease (FMD) is a highly contagious disease that affects cloven-hoof animals including cattle, swine, sheep, goats, and lots of wild species. Effectively control measures are urged needed. Here, we showed that homoharringtonine treatment exhibited a strong inhibitory effect against two different strains of FMDVs (O/MYA98/BY/2010 and A/GD/MM/2013) in swine kidney (IBRS-2) cells. Further experiments demonstrated that homoharringtonine did not affect virus attachment or entry. Using time-of-addition assays, we found that the antiviral activity of homoharringtonine occurred primarily during the early stage of infection. These results demonstrated that homoharringtonine might be an effective anti-FMDV drug. Further studies are required to explore the antiviral activity of homoharringtonine against FMDV replication in vivo.


Asunto(s)
Antivirales/farmacología , Virus de la Fiebre Aftosa/efectos de los fármacos , Fiebre Aftosa/virología , Homoharringtonina/farmacología , Animales , Antivirales/química , Línea Celular , Virus de la Fiebre Aftosa/fisiología , Homoharringtonina/química , Humanos , Estructura Molecular , Internalización del Virus , Replicación Viral/efectos de los fármacos
17.
Arch. Clin. Psychiatry (Impr.) ; 46(2): 33-39, Mar.-Apr. 2019. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1011143

RESUMEN

Abstract Objective To compare sex difference in metabolic effect of olanzapine versus aripiprazole on schizophrenia. Methods A twelve-week prospective open-label cohort study to compare four subgroups according to first-episode schizophrenia patients' type of drug usage and sex: female aripiprazole (n = 11), male aripiprazole (n = 11), female olanzapine (n = 10), and male olanzapine (n = 11) for body mass index, fasting serum triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose. Results Aripiprazole may be associated with weight gain in female patients with low-baseline weight. Aripiprazole may have an adverse effect of weight and favorable effects of circulating glucose and lipid on female over male schizophrenia patients. The aripiprazole-induced changes in glucose and lipid may be independent of body fat storage, especially for female schizophrenia patients. Olanzapine may have adverse effects of weight, glucose and lipid profiles on female over male schizophrenic patients. Discussion Our findings fill the gap in knowledge and provide a sex-specific guidance to psychiatrist better tailoring treatment to individual sex-differential characteristics and a key clue to understand the sex-differential mechanism of antipsychotics-induced metabolic dysfunction.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Glucemia/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Aripiprazol/efectos adversos , Olanzapina/efectos adversos , Esquizofrenia/tratamiento farmacológico , Triglicéridos/sangre , Aumento de Peso/efectos de los fármacos , Índice de Masa Corporal , Factores Sexuales , Estudios Prospectivos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre
18.
J Med Virol ; 91(2): 208-214, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30039874

RESUMEN

Foot-and-mouth disease (FMD) is a disease of worldwide economic importance, and vaccines play an important role in preventing FMDV outbreaks. However, new control strategies are still needed since FMDV outbreaks still occur in some disease-free countries. Currently, interferon (IFN)-based strategies have been demonstrated to be an efficient biotherapeutic option against FMDV; however, interferon omega (IFN-ω) has not yet been assessed in this capacity. Thus, this study evaluated the antiviral activity of porcine IFN omega 7 (PoIFN-ω7) against FMDV. After the PoIFN-ω7 was expressed and purified, cell proliferation assays and quantitative real-time reverse transciption-polymerase chain reaction were used to evaluate the effective anti-cytopathic concentration of PoIFN-ω7 and its effectiveness pre- and post-infection with FMDV in swine kidney cells (IBRS-2). Results showed the rHis-PoIFN-ω7 fusion protein was considerably expressed using Escherichia coli BL21 (DE3) strain, and the recombinant protein exhibited significant in vitro protection against FMDV, including two strains belonging to type O and A FMDV, respectively. In addition, PoIFN-ω7 upregulated the transcription of Mx1, ISG15, OAS1, and PKR genes. These findings indicated that IFN-ω has the potential for serving as a useful therapeutic agent to prevent FMDV or other viral outbreaks in pigs.


Asunto(s)
Antivirales/farmacología , Virus de la Fiebre Aftosa/efectos de los fármacos , Virus de la Fiebre Aftosa/crecimiento & desarrollo , Interferón Tipo I/farmacología , Proteínas Recombinantes de Fusión/farmacología , Animales , Efecto Citopatogénico Viral , Interferón Tipo I/genética , Proteínas Recombinantes de Fusión/genética , Porcinos
19.
Mater Sci Eng C Mater Biol Appl ; 94: 1-10, 2019 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-30423681

RESUMEN

Hydrothermal method is an easy-to-use approach for creating nanostructured surfaces on titanium (Ti). However, whether the alkali conditions of this method influence the osteogenic potential of the modified surfaces remains unknown. In this study, we fabricated nanostructured surfaces, termed the Ti-1, Ti-5, and Ti-10 groups, by using the hydrothermal method in 1 M, 5 M, and 10 M NaOH aqueous solutions, respectively. An untreated Ti surface served as a control. The osteogenic performance of modified surfaces was systemically investigated, including the proliferation and osteogenic differentiation of human osteoblast-like MG63 cells in vitro and the osteointegration of implants in a rabbit femoral condyle defect model. After hydrothermal treatment, the hydrophilicity of modified surfaces was greatly enhanced. The Ti-1 group showed a nanowire-like topography, while the Ti-5 and Ti-10 groups exhibited a nanopetal-like topography with different pore sizes. Compared with the untreated Ti surface, the modified surfaces showed good cytocompatibility and enhanced the osteogenic differentiation of MG-63 cells. Compared with the other modified surfaces, the Ti-5 group was the most favourable for the osteogenic differentiation of cells, showing higher levels of alkaline phosphatase activity, osteogenic gene expression, mineralization and osteoprotegerin secretion. Twelve weeks after implantation at the bone defects, the Ti-5 group showed superior peri-implant bone regeneration and higher peak push-out force than the other groups. Overall, this study revealed the crucial role of alkali conditions of hydrothermal method in modulating the material characteristics of modified surfaces and their osteogenic performance in vitro and in vivo, highlighting the need for optimizing the processing conditions of hydrothermal method for enhanced osteointegration.


Asunto(s)
Álcalis/farmacología , Nanoestructuras/química , Osteogénesis/efectos de los fármacos , Prótesis e Implantes , Temperatura , Titanio/farmacología , Agua/química , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Nanoestructuras/ultraestructura , Oseointegración/efectos de los fármacos , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Conejos , Propiedades de Superficie , Microtomografía por Rayos X
20.
Microb Pathog ; 127: 79-84, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30500407

RESUMEN

Recently, a novel type I interferon alphaomega (IFN-αω), also known as IFN-µ, was identified. However, the biological activity of IFN-αω remain poorly understood. In this study, the porcine IFN-αω (PoIFN-αω) was expressed, purified, and its antiviral activities assessed by its ability to inhibit the cytopathic effect caused by FMDV on IBRS-2 cells. In addition, q-PCR was used to evaluate the expression of IFN-stimulated genes induced by PoIFN-αω. It was found that PoIFN-αω exerted effective antiviral activity against FMDV pre- and post-infection. Additionally, PoIFN-αω induced the transcription of IFN-stimulated genes, including Mx1, ISG15, OAS1, and PKR genes. Our study reported a new indication of PoIFN-αω as an effective anti-FMDV agent for the first time.


Asunto(s)
Antivirales/farmacología , Virus de la Fiebre Aftosa/efectos de los fármacos , Interferón Tipo I/farmacología , Proteínas Recombinantes/farmacología , Animales , Antivirales/aislamiento & purificación , Antivirales/metabolismo , Línea Celular , Efecto Citopatogénico Viral , Perfilación de la Expresión Génica , Factores Inmunológicos/biosíntesis , Interferón Tipo I/genética , Interferón Tipo I/aislamiento & purificación , Interferón Tipo I/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Porcinos
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