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1.
Protein Expr Purif ; 226: 106611, 2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39317297

RESUMEN

Bovine viral diarrhea virus (BVDV) is a significant immunosuppressive pathogen that has a major impact on the global cattle industry. Research efforts are currently focused on the envelope glycoprotein E2 of BVDV to improve immune responses. However, the full-length E2 protein is not ideal as an immune antigen and diagnostic tool, leading to the exploration of alternative strategies. In this study, we optimized the E2 gene using IDEB and ExpOptimizer software, then expressed the E2 gene using both baculovirus and E. coli expression systems. Subsequently, we assessed the immunogenicity of the purified E2 protein in mice and its application in indirect ELISA assays. Our findings showed that the Bac-E2 protein produced by the baculovirus system induced higher levels of antibody production and splenic lymphocyte proliferation in mice compared to the E. coli system. Moreover, the indirect ELISA assay developed using Bac-E2 protein exhibited superior specificity, sensitivity, and accuracy in comparison to the E. coli-expressed E2 ELISA. Overall, our study demonstrates that the optimized E2 protein generated through a baculovirus expression system elicits robust humoral and cellular immune responses in mice, making it a promising candidate for vaccine development. Furthermore, the optimized E2 protein ELISA assay shows enhanced sensitivity and accuracy, suggesting its potential as a valuable diagnostic antigen.

2.
J Med Virol ; 94(10): 4918-4925, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35644833

RESUMEN

The West Nile virus (WNV) is a member of the flavivirus and is known to cause encephalitis. There is currently no specific treatment for WNV infection. Repurposing of clinically approved drugs appeared promising for rapidly identifying effective, safe, and readily available candidates for antiviral drugs. Here, we screened the small-molecule compounds with anti-WNV activity from 978 Food Drug Administration-approved drugs. Four compounds, including cilnidipine, mycophenolate mofetil, nitazoxanide, and teriflunomide, were found to efficiently abrogate WNV infection in Vero cells and human neuroblastoma SH-SY5Y cells. The four compounds also exert broad-spectrum antiviral activity against the Zika virus, Japanese encephalitis virus, yellow fever virus, tick-borne encephalitis virus, and chikungunya virus. Furthermore, nitazoxanide (a synthetic benzamide) and teriflunomide (an inhibitor of dihydroorotate dehydrogenase, DHODH) protected 20% and 40% of mice from lethal WNV challenge, respectively. Both drugs, which are orally bioavailable and have been approved clinically for many years, may be promising therapeutics for WNV infection. Moreover, the other two DHODH inhibitors, ML390 and vidofludimus, also displayed potent activity against WNV infection in vitro and in vivo.


Asunto(s)
Flavivirus , Neuroblastoma , Fiebre del Nilo Occidental , Virus del Nilo Occidental , Infección por el Virus Zika , Virus Zika , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Chlorocebus aethiops , Humanos , Ratones , Neuroblastoma/tratamiento farmacológico , Células Vero , Infección por el Virus Zika/tratamiento farmacológico
3.
J Med Virol ; 94(10): 4809-4819, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35733297

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh member of the coronavirus family that can infect humans. Recently, more contagious and pathogenic variants of SARS-CoV-2 have been continuously emerging. Clinical candidates with high efficacy and ready availability are still in urgent need. To identify potent anti-SARS-CoV-2 repurposing drugs, we evaluated the antiviral efficacy of 18 selective estrogen receptor modulators (SERMs) against SARS-CoV-2 infection. Six SERMs exhibited excellent anti-SARS-CoV-2 effects in Vero E6 cells and three human cell lines. Clomifene citrate, tamoxifen, toremifene citrate, and bazedoxifene acetate reduced the weight loss of hamsters challenged with SARS-CoV-2, and reduced hamster pulmonary viral load and interleukin-6 expression when assayed at 4 days postinfection. In particular, bazedoxifene acetate was identified to act on the penetration stage of the postattachment step via altering cholesterol distribution and endosome acidification. And, bazedoxifene acetate inhibited pseudoviruses infection of original SARS-CoV-2, Delta variant, Omicron variant, and SARS-CoV. These results offer critical information supporting bazedoxifene acetate as a promising agent against coronaviruses.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Antivirales/farmacología , Humanos , Indoles , Moduladores Selectivos de los Receptores de Estrógeno/farmacología
4.
BMC Vet Res ; 16(1): 474, 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33276787

RESUMEN

BACKGROUND: Foot-and-mouth disease (FMD) is a highly transmissible disease that leads to vast economic losses in many countries. Prevention using inactivated vaccines is one effective measure used to control FMD. Unfortunately, inactivated FMD vaccines provide only short-term protection and require a cold-chain system. In recent years, many studies have shown that layered double metal hydroxides (LDHs) carrying antigens can be used to strongly induce immune responses. In this study, LDH nanoparticles (NPs) were prepared by hydrothermal synthesis. LDH particle size, electric potential, and morphology were measured and observed. The adsorption capacity of LDH NPs to FMDV was tested. The effects of LDH as an adjuvant on inactivated FMDV vaccines were further evaluated and compared with commercial FMDV Montanide ISA-206 in BALB/C female mice and Yorkshire pigs. RESULTS: LDH NPs were successfully prepared with a uniform particle size of ~ 87.21 nm, regular edges, a loose hexagonal shape and positive zeta charge of 32 mV. The maximum absorption concentration was 0.16-0.31 µg FMDV/µg LDH. In the mouse experiment, antibody levels in group LDH + FMDV were significantly higher compared to group saline + FMDV (P < 0.01) from days 42-98 and were significantly higher to group ISA-206 + FMDV on day 56 post-immunization (P < 0.05). After day 14 post-immunization, IFN-γ content was significantly increased (P < 0.05). In the pig experiment, antibody levels in both the ISA-206 + FMDV and LDH + FMDV were positive and were significantly higher compared with the PBS group on day 7 (P < 0.005). Antibody levels in 90% pigs were positive on day 56 in the LDH group. The neutralizing antibody levels in the LDH and ISA-206 groups were significantly higher from days 7-28 compared to the PBS control group (P < 0.05). Thus, LDH NPs were effective at inducing an immune response against FMDV. CONCLUSIONS: LDHs with a loose hexagonal shape and a positive charge were prepared and evaluated as adjuvant for FMD vaccine. It was demonstrated that LDHs can induce immune responses in mice and pigs. In addition, the LDHs produced antibodies continuously which may indicate a slow-release effect. The study shows that LDHs may act as a potentially useful FMDV adjuvant.


Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Fiebre Aftosa/prevención & control , Enfermedades de los Porcinos/prevención & control , Vacunas de Productos Inactivados/uso terapéutico , Animales , Anticuerpos Neutralizantes/inmunología , Femenino , Fiebre Aftosa/inmunología , Virus de la Fiebre Aftosa , Hidróxidos , Ratones Endogámicos BALB C , Nanopartículas/administración & dosificación , Nanopartículas/química , Sus scrofa , Porcinos , Enfermedades de los Porcinos/inmunología , Vacunación/veterinaria , Vacunas de Productos Inactivados/inmunología , Vacunas Virales
5.
Mikrochim Acta ; 185(3): 163, 2018 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-29594795

RESUMEN

The authors have developed a homogeneous "off-on" fluorometric method for the determination of the antibiotic sulfamethazine (SMZ). Aptamer against SMZ was labeled with graphene oxide quantum dots upon which the Graphene oxide quenched the blue fluorescence of the GOQDs. On addition of SMZ, the aptamers will bind SMZ and this will cause the release of GOQDs. As a result, fluorescence will be regenerated. Fluorescence, best measured at excitation/emission wavelengths of 365/455 nm, increases linearly in the 8 pg·mL-1 to 60 ng·mL-1 SMZ concentration range, with a 5 pg·mL-1 detection limit. The method is reliable and was successfully applied to the determination of SMZ in spiked milk samples, with recoveries ranging from 89 to 96% depending on analyte concentration. Graphical abstract Graphene oxide quantum dots (GOQDs) were covalently bound to the aptamer (apt) against sulfamethazine (SMZ) and adsorbed on the surface of graphene oxide (GO). This results in quenching of the fluorescence of GOQDs. On addition of SMZ, fluorescence is restored due to the release of GOQD@apt from GO.

6.
Bioorg Med Chem Lett ; 27(24): 5446-5449, 2017 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-29138025

RESUMEN

To follow up on our recent discovery of the 18-amino acid all-hydrocarbon [i, i + 4]-stapled p110α[E545K] peptide 1 that was shown to potently block the intracellular p110α[E545K]-IRS1 interaction (a protein-protein interaction uniquely present in cancer cells expressing p110α[E545K]) and the growth of the xenograft tumors formed by cancers harboring this mutation, in the current study we prepared and examined six derivatives of 1, i.e. stapled peptides 2-A, 2-B, 3-A, 3-B, 4-A, 4-B. We found that 2-A, 2-B, 4-A, and 4-B had higher % α-helicity than 1; moreover, the enhanced % α-helicity also led to an enhanced proteolytic stability. When compared with 1, the structurally simplified 14-amino acid 4-A and 4-B were found to more potently deactivate the AKT phosphorylation at Ser473 in the p110α[E545K]-expressing colon cancer cells, whose activation was previously demonstrated by us to be specifically derived from the p110α[E545K]-IRS1 interaction. The preliminary findings from the current study have laid a foundation for future more extensive studies on the stapled p110α[E545K] peptides newly identified in the current study.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Hidrocarburos/química , Proteínas Sustrato del Receptor de Insulina/metabolismo , Péptidos/química , Línea Celular Tumoral , Dicroismo Circular , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I/genética , Humanos , Proteínas Sustrato del Receptor de Insulina/antagonistas & inhibidores , Mutación , Resonancia Magnética Nuclear Biomolecular , Péptidos/síntesis química , Péptidos/farmacología , Fosforilación/efectos de los fármacos , Mapas de Interacción de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo
7.
Qual Life Res ; 26(9): 2321-2331, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28421384

RESUMEN

PURPOSE: This study was to evaluate the efficacy of a complementary Chinese treatment modality Guolin-Qigong (GLQG) for patients with breast cancer on the body-mind health. METHODS: A randomized controlled clinical trial was conducted among 158 women with breast cancer. Subjects were randomized to receive GLQG (test group) versus a physical stretching program (control group) following conventional treatment for breast cancer. GLQG and stretching interventions were performed twice a week over 24 weeks. The primary outcome was the change in quality of life (QoL). Secondary outcome measures included anxiety, depression, and clinical indicators. All participants were assessed at four time-points, at the beginning of the study (T1), after 12 weeks of the intervention (T2), immediately after 24-week intervention (T3), and at 48-week follow-up visit (T4). RESULTS: Improvements in QoL were evident in both groups but the test group fared better than the control group at the 12th week (P < 0.01) and particularly in emotional well-being (P < 0.01) and breast cancer-specific well-being (P < 0.001). The test group showed an improvement in anxiety levels (P < 0.01), whereas the control group showed improvements in depression (P < 0.05) but there was no significant difference between groups (P > 0.05). Both groups showed improvements in immunological function and the test group fared better than the control in TNF-α levels (P < 0.05). The results in subjects who practiced more than 4 times and 6 h per week were similar to that of all subjects; however, the improvement in anxiety in the GLQG group was more obvious. There are positive correlations between QoL and anxiety and depression. CONCLUSIONS: Both GLQG and physical stretching are beneficial during recovery following breast cancer. GLQC was more effective in terms of Qol improvements than physical stretching. Both programs brought improvements in anxiety or depression but had were comparable. GLQC group had a greater effect on immunological function than physical exercise.


Asunto(s)
Neoplasias de la Mama/psicología , Qigong/métodos , Calidad de Vida/psicología , Femenino , Humanos , Persona de Mediana Edad
8.
Can J Physiol Pharmacol ; 95(9): 1030-1038, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28511026

RESUMEN

We previously suggested that endogenous glucocorticoids (GCs) may inhibit myocardial inflammation induced by lipopolysaccharide (LPS) in vivo. However, the possible cellular and molecular mechanisms were poorly understood. In this study, we investigated the role of physiological concentration of GCs in inflammation induced by LPS in cardiac fibroblasts and explored the possible mechanisms. The results showed that hydrocortisone at the dose of 127 ng/mL (equivalent to endogenous basal level of GCs) inhibited LPS (100 ng/mL)-induced productions of TNF-α and IL-1ß in cardiac fibroblasts. Xanthine oxidase/xanthine (XO/X) system impaired the anti-inflammatory action of GCs through downregulating HDAC2 activity and expression. Knockdown of HDAC2 restrained the anti-inflammatory effects of physiological level of hydrocortisone, and blunted the ability of XO/X system to downregulate the inhibitory action of physiological level of hydrocortisone on cytokines. These results suggested that HDAC2 was required by the physiological concentration of GC to inhibit inflammatory response. The dysfunction of HDAC2 induced by oxidative stress might be account for GC resistance and chronic inflammatory disorders during the cardiac diseases.


Asunto(s)
Antiinflamatorios/farmacología , Fibroblastos/efectos de los fármacos , Glucocorticoides/farmacología , Histona Desacetilasa 2/metabolismo , Miocardio/patología , Animales , Antiinflamatorios/uso terapéutico , Citocinas/biosíntesis , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Fibroblastos/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucocorticoides/uso terapéutico , Hidrocortisona/farmacología , Hidrocortisona/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Xantina/metabolismo , Xantina Oxidasa/metabolismo
10.
Chem Soc Rev ; 44(15): 5246-64, 2015 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-25955411

RESUMEN

The sirtuin family of enzymes are able to catalyze the N(ε)-acyl-lysine deacylation reaction on histone and non-histone protein substrates. Over the past years since the discovery of its founding member (i.e. the yeast silent information regulator 2 (sir2) protein) in 2000, the sirtuin-catalyzed deacylation reaction has been demonstrated to play an important regulatory role in multiple crucial cellular processes such as transcription, DNA damage repair, and metabolism. This reaction has also been regarded as a current therapeutic target for human diseases such as cancer, and metabolic and neurodegenerative diseases. The unique ß-nicotinamide adenine dinucleotide (ß-NAD(+) or NAD(+))-dependent nature of the sirtuin-catalyzed deacylation reaction has also engendered extensive mechanistic studies, resulting in a mechanistic view of the enzyme chemistry supported by several lines of experimental evidence. On the journey toward these knowledge advances, chemical biological means have constituted an important functional arsenal; technically, a variety of chemical probes and modulators (inhibitors and activators) have been developed and some of them have been employed toward an enhanced mechanistic and functional (pharmacological) understanding of the sirtuin-catalyzed deacylation reaction. On the other hand, an enhanced mechanistic understanding has also facilitated the development of a variety of chemical probes and modulators. This article will review the tremendous accomplishments achieved during the past few years in the field of sirtuin chemical biology. It is hoped that this would also help to set a stage for how outstanding mechanistic and functional questions for the sirtuin-catalyzed deacylation reaction could be addressed in the future from the chemical biology perspective.


Asunto(s)
Sirtuinas , Animales , Bioquímica , Proteínas Fúngicas , Humanos , Ratones
11.
Biochem Biophys Res Commun ; 457(3): 419-25, 2015 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-25582777

RESUMEN

Sonic hedgehog (Shh) pathway has been reported to protect cardiomyocytes in myocardial infarction (MI), but the underlying mechanism is not clear. Here, we provide evidence that Shh pathway induces cardiomyocytes survival through AMP-activated protein kinase-dependent autophagy. Shh pathway agonist SAG increased the expression of LC3-II, and induced the formation of autophagosomes in cultured H9c2 cardiomyocytes under oxygen glucose deprivation (OGD) 1 h and 4 h. Moreover, SAG induced a profound AMP-activated protein kinase (AMPK) activation, and then directly phosphorylated and activated the downstream autophagy initiator Ulk1, independent of the autophagy suppressor mammalian target of rapamycin (mTOR) complex 1. Taken together, our results have shown that Shh activates AMPK-dependent autophagy in cardiomyocytes under OGD, suggesting a role of autophagy in Shh-induced cellular protection.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/fisiología , Proteínas Hedgehog/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Animales , Cardiotónicos/metabolismo , Hipoxia de la Célula , Línea Celular , Supervivencia Celular/fisiología , Glucosa/deficiencia , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Ratas , Transducción de Señal
12.
Org Biomol Chem ; 13(42): 10442-50, 2015 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-26418815

RESUMEN

Built upon the catalytic mechanism-based pan-SIRT1/2/3 inhibitory warhead L-2-amino-7-carboxamidoheptanoic acid (L-ACAH, a close structural analog of N(ε)-acetyl-lysine) that our laboratory discovered recently, in the current study, its carboxamide NH2-ethylated analog was found to be a ∼2.4-6.6-fold stronger SIRT1/2/3 inhibitory warhead than L-ACAH. Carboxamide NH2-dodecylated and carboxymethylated analogs of L-ACAH were also identified as potent SIRT6 and SIRT5 inhibitory warheads, respectively.


Asunto(s)
Ácidos Heptanoicos/química , Lisina/química , Sirtuinas/antagonistas & inhibidores , Sirtuinas/química , Bibliotecas de Moléculas Pequeñas/síntesis química , Concentración 50 Inhibidora , Espectrometría de Masas , Estructura Molecular , Bibliotecas de Moléculas Pequeñas/química
13.
J Transl Med ; 12: 140, 2014 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-24886055

RESUMEN

BACKGROUND: Traditional Chinese Medicine Constitution (TCMC) refers to an integrated, metastable and natural specialty of individual in morphosis, physiological functions and psychological conditions. It is formed on the basis of innate and acquired endowments in the human life process, which can be divided into normal constitution and unbalanced ones. The aim of this study was to investigate the distribution of TCMCs of Chinese women in Hong Kong and its acquired influencing factors. METHODS: Local Chinese women between 30 to 65 years old, were recruited from 18 districts of Hong Kong (n=944), and were assessed using the Traditional Chinese Medicine Physical Constitution Scale for their TCMC types. Social-demographic, reproductive, lifestyle, systemic health and emotional status information were collected through structured questionnaire. The associations between different independent factors and each TCMC type, as well as the complex unbalanced TCMC types were tested individually. Significant factors related to unbalanced TCMC types were identified in final models using multiple factor analysis. RESULTS: A total of 764 (80.9%) participants were diagnosed with unbalanced TCMCs. The most common TCMC type was Qi-deficiency constitution (53.9%), followed by Phlegm-wetness (38.9%), Yang-deficiency (38.2%), Yin-deficiency (35.5), Blood-stasis (35.4) and Qi-depressed (31%) constitution. Six hundred and eleven participants (64.7%) had at least two types of combined and unbalanced constitutions. Stepwise logistic analysis indicated that poor systemic health condition (OR, 1.76-2.89), negative emotions (OR=1.39), overweight (OR=1.58), high educational level (OR=1.18) and mental work (OR=1.44) were significantly positively correlated with certain unbalanced TCMCs. Meanwhile, aging (OR, 0.59-0.73), exercise habit (OR, 0.61-0.79) and reproductive history (OR=0.72) showed inverse associations with unbalanced constitutions. In addition, systemic health condition and emotional status, exercise habit and age were significantly associated with the combined unbalanced TCMC types. CONCLUSION: The majority of middle-aged Chinese women in Hong Kong had unbalanced and complex TCMCs. Qi-deficiency, Phlegm-wetness and Yang-deficiency constitutions are the most common constitutions. Poor systemic health condition, less-than-satisfactory emotional life, overweight and mental work are associated with and may be contributors for the formation of unbalanced TCMCs, while regular physical exercise was found to be a potential protective factor for unbalanced TCMCs.


Asunto(s)
Medicina Tradicional China , Adulto , Anciano , Estudios Transversales , Femenino , Hong Kong , Humanos , Persona de Mediana Edad
14.
Poult Sci ; 103(11): 104164, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39208487

RESUMEN

We previously identified a dark blue appearance through the skin of abdomen, especially the colored chicken breeds, called hyperpigmentation of the visceral peritoneum (HVP) which characterized by intense pigmentation of connective tissue in the visceral peritoneum. The HVP has recently garnered increasing attention due to its negative impact on carcass appearance, and been an important concern in the poultry industry, especially for the Chinese yellow-feathered broilers. In this study, we measured the in vivo HVP at different time points, and analyzed the correlation between the HVP in vivo and postmortem. Then, established an accurate and reliable HVP phenotypic measuring method in vivo for early selection in chickens and analyzed the association of phenotypic variations with the in vivo HVP traits with growth traits. The results showed that the in vivo HVP at 21 d of age in chickens have a high heritability (h2 = 0.452) through estimating genetic parameters, and in vivo HVP levels at 21 and 42 d were both significantly associated with those postmortem in chickens, suggesting that directional selection on reducing HVP can be implemented as early as at 21 d in the breeding and production of chickens. Although, we found HVP had no effect on the body weight at 1 d, it could significantly reduce the body weight at 21, 42, 70 d and 91 d in chickens. This suggests HVP not only has a negative effect on carcass traits, but also significantly reduces the production in the poultry industry.


Asunto(s)
Peso Corporal , Pollos , Peritoneo , Animales , Femenino , Masculino , Cruzamiento , Pollos/genética , Pollos/fisiología , Pollos/crecimiento & desarrollo , Hiperpigmentación/veterinaria , Hiperpigmentación/genética , Fenotipo , Pigmentación/genética , Selección Genética
15.
Pharmaceutics ; 16(9)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39339151

RESUMEN

Diseases transmitted by arthropod-borne viruses such as West Nile virus (WNV) and chikungunya virus (CHIKV) pose threat to global public health. Unfortunately, to date, there is no available approved drug for severe symptoms caused by both viruses. It has been reported that reverse transcriptase inhibitors can effectively inhibit RNA polymerase activity of RNA viruses. We screened the anti-WNV activity of the FDA-approved reverse transcriptase inhibitor library and found that 4 out of 27 compounds showed significant antiviral activity. Among the candidates, etravirine markedly inhibited WNV infection in both Huh 7 and SH-SY5Y cells. Further assays revealed that etravirine inhibited the infection of multiple arboviruses, including yellow fever virus (YFV), tick-borne encephalitis virus (TBEV), and CHIKV. A deeper study at the phase of action showed that the drug works primarily during the viral replication process. This was supported by the strong interaction potential between etravirine and the RNA-dependent RNA polymerase (RdRp) of WNV and alphaviruses, as evaluated using molecular docking. In vivo, etravirine significantly rescued mice from WNV infection-induced weight loss, severe neurological symptoms, and death, as well as reduced the viral load and inflammatory cytokines in target tissues. Etravirine showed antiviral effects in both arthrophlogosis and lethal mouse models of CHIKV infection. This study revealed that etravirine is an effective anti-WNV and CHIKV arbovirus agent both in vitro and in vivo due to the inhibition of viral replication, providing promising candidates for clinical application.

16.
Viruses ; 16(8)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39205296

RESUMEN

Chikungunya virus (CHIKV) is a reemerging arbovirus causing disease on a global scale, and the potential for its epidemics remains high. CHIKV has caused millions of cases and heavy economic burdens around the world, while there are no available approved antiviral therapies to date. In this study, nifuroxazide, an FDA-approved antibiotic for acute diarrhea or colitis, was found to significantly inhibit a variety of arboviruses, although its antiviral activity varied among different target cell types. Nifuroxazide exhibited relatively high inhibitory efficiency in yellow fever virus (YFV) infection of the hepatoma cell line Huh7, tick-borne encephalitis virus (TBEV) and west nile virus (WNV) infection of the vascular endothelial cell line HUVEC, and CHIKV infection of both Huh7 cells and HUVECs, while it barely affected the viral invasion of neurons. Further systematic studies on the action stage of nifuroxazide showed that nifuroxazide mainly inhibited in the viral replication stage. In vivo, nifuroxazide significantly reduced the viral load in muscles and protected mice from CHIKV-induced footpad swelling, an inflammation injury within the arthrosis of infected mice. These results suggest that nifuroxazide has a potential clinical application as an antiviral drug, such as in the treatment of CHIKV infection.


Asunto(s)
Antivirales , Fiebre Chikungunya , Virus Chikungunya , Hidroxibenzoatos , Nitrofuranos , Replicación Viral , Animales , Ratones , Humanos , Virus Chikungunya/efectos de los fármacos , Virus Chikungunya/fisiología , Antivirales/farmacología , Antivirales/uso terapéutico , Replicación Viral/efectos de los fármacos , Nitrofuranos/farmacología , Nitrofuranos/uso terapéutico , Fiebre Chikungunya/tratamiento farmacológico , Fiebre Chikungunya/virología , Hidroxibenzoatos/farmacología , Hidroxibenzoatos/uso terapéutico , Línea Celular , Carga Viral/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana
17.
Theranostics ; 14(9): 3423-3438, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948056

RESUMEN

PRL1 and PRL3, members of the protein tyrosine phosphatase family, have been associated with cancer metastasis and poor prognosis. Despite extensive research on their protein phosphatase activity, their potential role as lipid phosphatases remains elusive. Methods: We conducted comprehensive investigations to elucidate the lipid phosphatase activity of PRL1 and PRL3 using a combination of cellular assays, biochemical analyses, and protein interactome profiling. Functional studies were performed to delineate the impact of PRL1/3 on macropinocytosis and its implications in cancer biology. Results: Our study has identified PRL1 and PRL3 as lipid phosphatases that interact with phosphoinositide (PIP) lipids, converting PI(3,4)P2 and PI(3,5)P2 into PI(3)P on the cellular membranes. These enzymatic activities of PRLs promote the formation of membrane ruffles, membrane blebbing and subsequent macropinocytosis, facilitating nutrient extraction, cell migration, and invasion, thereby contributing to tumor development. These enzymatic activities of PRLs promote the formation of membrane ruffles, membrane blebbing and subsequent macropinocytosis. Additionally, we found a correlation between PRL1/3 expression and glioma development, suggesting their involvement in glioma progression. Conclusions: Combining with the knowledge that PRLs have been identified to be involved in mTOR, EGFR and autophagy, here we concluded the physiological role of PRL1/3 in orchestrating the nutrient sensing, absorbing and recycling via regulating macropinocytosis through its lipid phosphatase activity. This mechanism could be exploited by tumor cells facing a nutrient-depleted microenvironment, highlighting the potential therapeutic significance of targeting PRL1/3-mediated macropinocytosis in cancer treatment.


Asunto(s)
Pinocitosis , Proteínas Tirosina Fosfatasas , Proteínas Tirosina Fosfatasas/metabolismo , Humanos , Línea Celular Tumoral , Animales , Proteínas de Neoplasias/metabolismo , Movimiento Celular , Ratones , Membrana Celular/metabolismo , Fosfatidilinositoles/metabolismo , Proteínas de la Membrana , Proteínas de Ciclo Celular
18.
Virology ; 588: 109900, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37832343

RESUMEN

Chikungunya virus (CHIKV) is a globally public health threat. There are currently no medications available to treat CHIKV infection. High-throughput screening of 419 kinase inhibitors was performed based on the cytopathic effect method, and six kinase inhibitors with reduced cytopathic effects, including tyrphostin AG879 (AG879), tyrphostin 9 (A9), sorafenib, sorafenib tosylate, regorafenib, and TAK-632, were identified. The anti-CHIKV activities of two receptor tyrosine kinase inhibitors, AG879 and A9, that have not been previously reported, were selected for further evaluation. The results indicated that 50% cytotoxic concentration (CC50) of AG879 and A9 in Vero cells were greater than 30 µM and 6.50 µM, respectively and 50% effective concentration (EC50) were 0.84 µM and 0.36 µM, respectively. The time-of-addition and time-of-removal assays illustrated that both AG879 and A9 function in the middle stage of CHIKV life cycle. Further, AG879 and A9 do not affect viral attachment; however, they inhibit viral RNA replication, and exhibit antiviral activity against CHIKV Eastern/Central/South African and Asian strains, Ross River virus and Sindbis virus in vitro.


Asunto(s)
Antineoplásicos , Fiebre Chikungunya , Virus Chikungunya , Animales , Chlorocebus aethiops , Humanos , Virus Chikungunya/genética , Células Vero , Tirfostinos/farmacología , Tirfostinos/uso terapéutico , Línea Celular , Antivirales/farmacología , Antivirales/uso terapéutico , Replicación Viral , Inhibidores de Proteínas Quinasas/farmacología , Antineoplásicos/farmacología
19.
Poult Sci ; 102(3): 102298, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36638759

RESUMEN

This study aimed to assess the effect of inbreeding on production traits using a long-term closed-line population recorded for residual feed intake (RFI). The study first used data from a previously reported population to determine the appropriate period of divergent selection for RFI. The results showed that RFI had similar moderate heritability estimates (0.28-0.34) during the fast-growing period (7-12 wk), and RFI at 7 to 10 wk had the highest heritability (0.34). Therefore, divergent selection was performed in a Chinese broiler population for RFI at 7 to 10 wk; the total sample size from generations zero (G0) to 13 was 9050. The divergence between the 2 lines increased steadily throughout generations, resulting in G13 with average RFI values of 304.55 in high RFI (HRFI) males, -160.31 in low RFI (LRFI) males, 296.30 in HRFI females and -157.55 in LRFI females. The feed intake (FI) and feed conversion ratio were almost higher in HRFI broilers than in LRFI broilers, and the magnitude of the difference in FI increased from approximately 4% for both sexes in G1 to approximately 33% in G13. Body weight gain was irregular from G1 to G13 and higher in LRFI broilers than in HRFI broilers after G10. Indeed, the HRFI broilers consumed more food, but they were lighter than LRFI broilers. In G13, LRFI males had heavier slaughter weight, longer cecum length, more white blood cells (WBC), red blood cells (RBC) and hemoglobin (HGB), but triglycerides, lower dressed percentage, percentage of half eviscerated yield, and eviscerated yield than HRFI males. LRFI females had a higher percentage of breast muscle and gizzard yield, longer cecum length, and more WBCs, RBCs and HGB but less abdominal fat and serum total cholesterol than HRFI females. This study was the first to verify that long-term divergent selection for RFI in Chinese broiler chickens is positive and beneficial.


Asunto(s)
Pollos , Ingestión de Alimentos , Animales , Femenino , Masculino , Alimentación Animal/análisis , Ciego , Pollos/genética , Fenotipo
20.
J Transl Med ; 10 Suppl 1: S12, 2012 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-23046537

RESUMEN

BACKGROUND: Chinese herbal medicine is increasingly widely used as a complementary approach for control of breast cancer recurrence and metastasis. In this paper, we examined the implicit prescription patterns behind the Chinese medicinal formulae, so as to explore the Chinese medicinal compatibility patterns or rules in the treatment or control of breast cancer recurrence and metastasis. METHODS: This study was based on the herbs recorded in Pharmacopoeia of the People's Republic of China, and the literature sources from Chinese Journal Net and China Master Dissertations Full-text Database (1990 - 2010) to analyze the compatibility rule of the prescription. Each Chinese herb was listed according to the selected medicinal formulae and the added information was organized to establish a database. The frequency and the association rules of the prescription patterns were analyzed using the SPSS Clenmentine Data Mining System. An initial statistical analysis was carried out to categorize the herbs according to their medicinal types and dosage, natures, flavors, channel tropism, and functions. Based on the categorization, the frequencies of occurrence were computed. RESULTS: The main prescriptive features from the selected formulae of the mining data are: (1) warm or cold herbs in the Five Properties category; sweet or bitter herbs in the Five Flavors category and with affinity to the liver meridian are the most frequently prescribed in the 96 medicinal formulae; (2) herbs with tonifying and replenishing, blood-activating and stasis-resolving, spleen-strengthening and dampness-resolving or heat-clearing and detoxicating functions that are frequently prescribed; (3) herbs with blood-tonifying, yin-tonifying, spleen-strengthening and dampness-resolving, heat-clearing and detoxicating, and blood-activating with stasis-resolving functions that are interrelated and prescribed in combination with qi-tonifying herbs. CONCLUSIONS: The results indicate that there is a close relationship between recurrence and metastasis of breast cancer with liver dysfunctions. These prescriptions focus on the herbs for nourishing the yin-blood, and emolliating and regulating the liver which seems to be the key element in the treatment process. Meanwhile, the use of qi-tonifying and spleen-strengthening herbs also forms the basis of prescription patterns.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/prevención & control , Minería de Datos , Prescripciones de Medicamentos , Medicamentos Herbarios Chinos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Femenino , Humanos , Medicina Tradicional China , Metástasis de la Neoplasia
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