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1.
J Med Virol ; 94(10): 4918-4925, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35644833

RESUMO

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.


Assuntos
Flavivirus , Neuroblastoma , Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Chlorocebus aethiops , Humanos , Camundongos , Neuroblastoma/tratamento farmacológico , Células Vero , Infecção por Zika virus/tratamento farmacológico
2.
J Med Virol ; 94(10): 4809-4819, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35733297

RESUMO

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.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Antivirais/farmacologia , Humanos , Indóis , Moduladores Seletivos de Receptor Estrogênico/farmacologia
3.
BMC Vet Res ; 16(1): 474, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276787

RESUMO

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.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Febre Aftosa/prevenção & controle , Doenças dos Suínos/prevenção & controle , Vacinas de Produtos Inativados/uso terapêutico , Animais , Anticorpos Neutralizantes/imunologia , Feminino , Febre Aftosa/imunologia , Vírus da Febre Aftosa , Hidróxidos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/química , Sus scrofa , Suínos , Doenças dos Suínos/imunologia , Vacinação/veterinária , Vacinas de Produtos Inativados/imunologia , Vacinas Virais
4.
Mikrochim Acta ; 185(3): 163, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29594795

RESUMO

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.

5.
Bioorg Med Chem Lett ; 27(24): 5446-5449, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29138025

RESUMO

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.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Hidrocarbonetos/química , Proteínas Substratos do Receptor de Insulina/metabolismo , Peptídeos/química , Linhagem Celular Tumoral , Dicroísmo Circular , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Classe I de Fosfatidilinositol 3-Quinases/genética , Humanos , Proteínas Substratos do Receptor de Insulina/antagonistas & inibidores , Mutação , Ressonância Magnética Nuclear Biomolecular , Peptídeos/síntese química , Peptídeos/farmacologia , Fosforilação/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo
6.
Qual Life Res ; 26(9): 2321-2331, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28421384

RESUMO

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.


Assuntos
Neoplasias da Mama/psicologia , Qigong/métodos , Qualidade de Vida/psicologia , Feminino , Humanos , Pessoa de Meia-Idade
7.
Can J Physiol Pharmacol ; 95(9): 1030-1038, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28511026

RESUMO

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.


Assuntos
Anti-Inflamatórios/farmacologia , Fibroblastos/efeitos dos fármacos , Glucocorticoides/farmacologia , Histona Desacetilase 2/metabolismo , Miocárdio/patologia , Animais , Anti-Inflamatórios/uso terapêutico , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/uso terapêutico , Hidrocortisona/farmacologia , Hidrocortisona/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Xantina/metabolismo , Xantina Oxidase/metabolismo
9.
Chem Soc Rev ; 44(15): 5246-64, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-25955411

RESUMO

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.


Assuntos
Sirtuínas , Animais , Bioquímica , Proteínas Fúngicas , Humanos , Camundongos
10.
Biochem Biophys Res Commun ; 457(3): 419-25, 2015 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-25582777

RESUMO

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.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/fisiologia , Proteínas Hedgehog/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Animais , Cardiotônicos/metabolismo , Hipóxia Celular , Linhagem Celular , Sobrevivência Celular/fisiologia , Glucose/deficiência , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Ratos , Transdução de Sinais
11.
Org Biomol Chem ; 13(42): 10442-50, 2015 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-26418815

RESUMO

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.


Assuntos
Ácidos Heptanoicos/química , Lisina/química , Sirtuínas/antagonistas & inibidores , Sirtuínas/química , Bibliotecas de Moléculas Pequenas/síntese química , Concentração Inibidora 50 , Espectrometria de Massas , Estrutura Molecular , Bibliotecas de Moléculas Pequenas/química
12.
J Transl Med ; 12: 140, 2014 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-24886055

RESUMO

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.


Assuntos
Medicina Tradicional Chinesa , Adulto , Idoso , Estudos Transversais , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade
13.
Theranostics ; 14(9): 3423-3438, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948056

RESUMO

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.


Assuntos
Pinocitose , Proteínas Tirosina Fosfatases , Proteínas Tirosina Fosfatases/metabolismo , Humanos , Linhagem Celular Tumoral , Animais , Proteínas de Neoplasias/metabolismo , Movimento Celular , Camundongos , Membrana Celular/metabolismo , Fosfatidilinositóis/metabolismo , Proteínas de Membrana , Proteínas de Ciclo Celular
14.
Virology ; 588: 109900, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37832343

RESUMO

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.


Assuntos
Antineoplásicos , Febre de Chikungunya , Vírus Chikungunya , Animais , Chlorocebus aethiops , Humanos , Vírus Chikungunya/genética , Células Vero , Tirfostinas/farmacologia , Tirfostinas/uso terapêutico , Linhagem Celular , Antivirais/farmacologia , Antivirais/uso terapêutico , Replicação Viral , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos/farmacologia
15.
Poult Sci ; 102(3): 102298, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36638759

RESUMO

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.


Assuntos
Galinhas , Ingestão de Alimentos , Animais , Feminino , Masculino , Ração Animal/análise , Ceco , Galinhas/genética , Fenótipo
16.
J Transl Med ; 10 Suppl 1: S12, 2012 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-23046537

RESUMO

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.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/prevenção & controle , Mineração de Dados , Prescrições de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Feminino , Humanos , Medicina Tradicional Chinesa , Metástase Neoplásica
17.
J Cardiovasc Pharmacol ; 60(1): 33-41, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22472906

RESUMO

Emerging evidence indicates that myocardial inflammation plays a key role in the pathogenesis of cardiac diseases. But the exact mechanisms for this chronic inflammatory disorder have not been elucidated. Glucocorticoids (GCs) are the most effective anti-inflammatory treatments available for many inflammatory diseases. However, it is unknown whether endogenous GCs are able to exert anti-inflammatory effect on myocardial inflammation. In this study, the potential role of endogenous GCs in the regulation of myocardial inflammation was investigated. We showed that the reduction of endogenous GC level by adrenalectomy promoted the production of basal and lipopolysaccharide (LPS)-induced proinflammatory cytokines, which could be partly reversed by supplementing with exogenous physiological level of hydrocortisone. Inhibition of GC receptor (GR) signaling pathway with GR antagonist mifepristone (RU486) or histone deacetylase inhibitor trichostatin A (TSA) also increased the levels of basal and LPS-induced proinflammatory cytokines. Moreover, blockade of GC-GR signaling pathway by adrenalectomy, RU486 or TSA enhanced LPS-induced myocardial nuclear factor-κB activation and histone acetylation but inhibited myocardial histone deacetylase expression and activity. Cardiac function studies demonstrated that blockade of the GC-GR signaling pathway aggravated inflammation-induced cardiac dysfunction. These findings indicate that endogenous GCs are able to inhibit myocardial inflammation induced by LPS. Endogenous GCs represent an important endogenous anti-inflammatory mechanism for myocardium in rats and such mechanism injury may be an important factor for pathogenesis of cardiac diseases.


Assuntos
Glucocorticoides/metabolismo , Inflamação/fisiopatologia , Miocárdio/patologia , Receptores de Glucocorticoides/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Histona Desacetilases/metabolismo , Hidrocortisona/administração & dosagem , Hidrocortisona/metabolismo , Ácidos Hidroxâmicos/farmacologia , Lipopolissacarídeos/toxicidade , Masculino , Mifepristona/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
18.
Front Psychol ; 13: 897425, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35814155

RESUMO

Despite a relatively large number of studies on teachers' identity development in the University-School community, few studies have explicitly focused on school EFL teachers' research identity construction. This study adopts the Activity Theory and examines three English as a foreign language (EFL) teachers from three middle schools in a University-School community in China. It investigates how three teachers constructed their research identity and what factors influenced the construction of their identities within the University-School activity system from the dual perspectives of the school and university teachers. Data are collected through semi-structured narrative interviews, triangulated by documents such as meeting minutes, and then analyzed by NVivo 12. The findings of this study show that (1) the University-School collaborative program helps form a University-School community of both teaching and research; (2) in this community, school EFL teachers continuously construct their identities in a spiral process of "practitioner" and "researcher"; (3) it highlights the internal factors containing the research experience and the stage of career and the external factors including the curriculum reform context and the communication in the community. The findings carry important implications for school EFL teachers' research identity construction and professional development in the University-School cooperation.

19.
World J Clin Cases ; 10(27): 9611-9618, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36186199

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) is a common surgical strategy for the treatment of early gastrointestinal tumors and precancerous lesions. PDCA nursing can effectively prevent potential risks in the nursing process, protect patient privacy, and improve patient satisfaction, nursing integrity, and service quality. AIM: To explore the effects of PDCA nursing model on the quality management of gastrointestinal ESD, the 36-item Shot-Form Health Survey (SF-36) score, and negative emotions. METHODS: A total of 178 patients who underwent ESD between January 2020 and January 2021 were divided into two groups. The usual care mode was the control group, with 80 cases from January to July 2020; from July 2020 to January 2021, 98 patients were enrolled in the PDCA care mode as the research group. The length of hospital stay and the costs of the two groups were statistically analyzed. The visual analog scale (VAS), SF-36 score, Zung self-rating scale for anxiety and depression, and postoperative complications were also assessed. RESULTS: The length of hospitalization and cost in the research group were lower than in the control group (P < 0.05), and the VAS scores were lower than those before care (P < 0.05). Moreover, the VAS score of the research group was lower than that of the control group (P < 0.05). The SF-36 scores for physical function, role status, social function, pain, mental health, and physical strength were higher in the research group than in the control group (P < 0.05). Depression and anxiety scores of the research group were lower than those of the control group (P < 0.05). The postoperative complication rate in the research group (6.12%) was lower than in the control group (32.50%) (P < 0.05). CONCLUSION: PDCA nursing can improve the quality of management of ESD surgery, shorten the length of hospital stay and cost, reduce the VAS and Zung scale scores to alleviate adverse emotions, improve the SF-36 score, and reduce postoperative complications.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 280: 121497, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-35749972

RESUMO

We successfully designed an aptasensor based on the red emission carbon dots (R-CDs) and effectively detected insulin (INS) via fluorescence resonance energy transfer (FRET). In the process, the aptamer (apt) labeled with R-CDs (R-CDs@apt) was used as fluorescence donor and graphene oxide (GO) was used as fluorescence receptor. The successful detection due to the aptamer sequence has a certain affinity for Go and INS, while the affinity for INS is stronger than that of GO. When INS is not added to the detection system, the aptamer is adsorbed onto the surface of GO, shortening the distance between R-CDs@apt and GO, resulting in FRET and the quenching of fluorescence of R-CDs@apt. When INS was added to the detection system, the aptamer selectively bound INS and separated from the adsorption of GO, FRET gradually disappeared and the fluorescence of R-CDs@apt/GO/INS system was restored. By comparing the changes of fluorescence intensity before and after adding INS, the detection of INS was implemented. The aptasensor has a good linear curve with the detection limit of as low as 1.1 nM when the concentration of INS reached 1.3-150 nM. This method has excellent selectivity and anti-interference. Therefore, it is a potential method for detecting substances in biological fluids.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Grafite , Pontos Quânticos , Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/métodos , Carbono , Transferência Ressonante de Energia de Fluorescência/métodos , Insulina , Limite de Detecção
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