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M2 protein of influenza virus plays an important role in virus budding, including membrane scission and vRNP packaging. Three hydrophobic amino acids (91F, 92V, and 94I) at the intracellular domain of the M2 protein constitute a hydrophobic motif, also known as the LC3-interacting region (LIR), whereas the role of this motif remains largely unclear. To explore the role of the 91-94 hydrophobic motif for influenza virus, all three hydrophobic amino acids were mutated to either hydrophilic S or hydrophobic A, resulting in two mutant viruses (WSN-M2/SSS and WSN-M2/AAA) in the background of WSN/H1N1. The results showed that the budding ability of the M2/SSS protein was inhibited and the bilayer membrane integrity of the WSN-M2/SSS virion was impaired based on transmission electron microscopy (TEM), which in turn abolished the resistance to trypsin treatment. Moreover, the mutant WSN-M2/SSS was dramatically attenuated in mice. In contrast, the AAA mutations did not have a significant effect on the budding of the M2 proteins or the bilayer membrane integrity of the viruses, and the mutant WSN-M2/AAA was still lethal to mice. In addition, although the 91-94 motif is an LIR, knocking out of the LC3 protein of A549 cells did not significantly affect the membrane integrity of the influenza viruses propagated on the LC3KO cells, which suggested that the 91-94 hydrophobic motif affected the viral membrane integrity and budding is independent of the LC3 protein. Overall, the hydrophobicity of the 91-94 motif is crucial for the budding of M2, bilayer membrane integrity, and pathogenicity of the influenza viruses. IMPORTANCE M2 plays a crucial role in the influenza virus life cycle. However, the function of the C-terminal intracellular domain of M2 protein remains largely unclear. In this study, we explored the function of the 91-94 hydrophobic motif of M2 protein. The results showed that the reduction of the hydrophobicity of the 91-94 motif significantly affected the budding ability of the M2 protein and impaired the bilayer membrane integrity of the mutant virus. The mouse study showed that the reduction of the hydrophobicity of the 91-94 motif significantly attenuated the mutant virus. All of the results indicated that the hydrophobicity of the 91-94 motif of the M2 protein plays an important role in budding, membrane integrity, and pathogenicity of influenza virus. Our study offers insights into the mechanism of influenza virus morphogenesis, particularly into the roles of the 91-94 hydrophobic motif of M2 in virion assembly and the pathogenicity of the influenza viruses.
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Subtipo H1N1 del Virus de la Influenza A , Proteínas de la Matriz Viral , Proteínas Viroporinas , Liberación del Virus , Aminoácidos/metabolismo , Animales , Interacciones Hidrofóbicas e Hidrofílicas , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/fisiología , Ratones , Proteínas de la Matriz Viral/metabolismo , Proteínas Viroporinas/metabolismoRESUMEN
Duck circovirus (DuCV) is one of the most prevalent viruses in the duck breeding industry, and causes persistent infection and severe immunosuppression. Currently, there is a serious lack of prevention and control measures and no commercial vaccine against DuCV. Therefore, effective antiviral drugs are important for treating DuCV infection. Interferon (IFN) is an important component of antiviral innate immunity, but it remains unclear whether duck IFN-α has a clinical effect against DuCV. Antibody therapy is an important way to treat viral infections. The DuCV structural protein (cap) is immunogenic, and it remains to be determined whether an anti-cap protein antibody can effectively block DuCV infection. In this study, the duck IFN-α gene and the DuCV structural protein cap gene were cloned, expressed and purified in Escherichia coli to prepare duck recombinant IFN-α and the cap protein. Then, rabbits were immunized with the recombinant cap protein to prepare a rabbit polyclonal antibody. This study investigated the antiviral effect of duck recombinant IFN-α and the anti-cap protein antibody and their combined effect on Cherry Valley ducks infected with DuCV. The results showed that the treatment significantly alleviated the clinical symptoms of immune organ atrophy and immunosuppression compared with the control. The histopathological damage of the target organs was alleviated, and replication of DuCV in the immune organs was significantly inhibited. The treatment also reduced the damage caused by DuCV to the liver and immune function, and increased the level of the DuCV antibody in the blood, thereby improving antiviral activity. Notably, the combination of duck IFN-α and the polyclonal antibody completely blocked DuCV infection after 13 days under the experimental conditions, showing a better inhibitory effect on DuCV infection than single treatments. These results showed that duck recombinant IFN-α and the anti-cap protein antibody can be used as antiviral drugs to clinically treat and control DuCV infection, particularly the vertical transmission of the virus in breeding ducks.
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Infecciones por Circoviridae , Circovirus , Enfermedades de las Aves de Corral , Animales , Conejos , Interferón-alfa/genética , Circovirus/genética , Proteínas Recombinantes/genética , Escherichia coli/genética , Infecciones por Circoviridae/prevención & control , Infecciones por Circoviridae/veterinaria , Antivirales/farmacología , Anticuerpos , Enfermedades de las Aves de Corral/tratamiento farmacológico , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Traditional Chinese medicine (TCM) prescription or rumen-protected GABA (RP-GABA) can effectively relieve the heat stress (HS) in cattle, but the joint effects of TCM and RP-GABA on HS in beef cattle are not fully clarified. To investigate the effects of TCM or/and RP-GABA on growth performance, antioxidant capacity, serum parameters and heat shock proteins (HSPs) expression in beef cattle under HS ambient. A total of 40 Jinjiang yellow cattle were randomly divided into four groups: (a) control group (basal diet, BD), (b) TCM group (BD+TCM), (c) GABA group (BD+RP-GABA) and (d) TCM+GABA group (BD+TCM plus RP-GABA). Results indicated that the average daily feed intake (ADFI) was significantly elevated in the TCM+GABA group (p < 0.05), whereas, average daily gain (ADG) was elevated (p < 0.05) in the group of TCM (38.5%), GABA (35.4%) and TCM+GABA (41.5%) compared with the control group. Meanwhile, TCM+GABA exhibited prominently more positive effects in terms of SOD, BUN, T-CHO, TG, HDL-C and HSP70 (p < 0.05 or p < 0.01) than the control and other treatment groups. Therefore, TCM or GABA can effectively moderate the HS response in beef cattle by ameliorating antioxidant capacity, serum parameters and HSPs expression, meanwhile, the combination of them exerts a synergistic effect on HS alleviation.
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Medicina Tradicional China , Rumen , Animales , Bovinos , Dieta/veterinaria , Suplementos Dietéticos/análisis , Respuesta al Choque Térmico , Calor , Prescripciones , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
BACKGROUND: Chaihu-Shugan-San (CSS), a Traditional Chinese Medicine formula, has been widely used for treating depression since the Ming Dynasty, as recorded in Jingyue Quanshu, but its effectiveness and safety lack comprehensive and objective evaluation. Based on our meta-analysis, we aimed to adequately evaluate the efficacy and risk of CSS by considering the latest clinical literature. METHODS: Multiple databases, including PubMed, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang, were used to collect clinical data. The quality of the included clinical studies was assessed using the Cochrane Risk of Bias Tool, and the data were meta-analyzed using Review Manager 5.0 and Stata 17. The data were obtained from a genome-wide association study, and Mendelian randomization (MR) was performed using R Software 4.3.2 with the TwoSampleMR and MR Pleiotropy RESidual Sum and Outlier packages. RESULTS: A total of 15 studies with 1034 patients and 6 antidepressant drugs were included in this work. Meta-analyses revealed that drug combinations of CSS and antidepressants significantly improved depressive symptoms (weighted mean differenceâ =â -4.21; 95% confidence interval [CI]: -5.62--2.81), increased the effective rate (odds ratio [OR]â =â 3.82; 95% CI: 2.44-6.83), and reduced side effects (ORâ =â -3.55; 95% CI: -5.66--1.43) compared with antidepressant monotherapy. Additionally, compared with antidepressant monotherapy, CSS alone exhibited fewer side effects (95% CI:-9.25--6.95). Like antidepressants, CSS also improved depressive symptoms (weighted mean differenceâ =â -0.05; 95% CI: -0.63--0.52) and increased the effective rate (ORâ =â 1.07; 95% CI: 0.52-2.20). Additionally, MR was used to evaluate the safety of traditional antidepressants, as there was a causal association between amitriptyline and body mass index. CONCLUSION: This analysis demonstrated that compared with traditional antidepressants, CSS combined with antidepressants was more effective and safer for treating depressed patients. MR showed that a causal relationship may exist between amitriptyline and body mass index. Therefore, clinicians should carefully consider the advantages and potential drawbacks of Traditional Chinese Medicine and classic drugs to serve patients better.
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Antidepresivos , Depresión , Humanos , Antidepresivos/uso terapéutico , Antidepresivos/efectos adversos , Depresión/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Extractos Vegetales/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare clinicopathological and imaging features of micro- and minitumors of the parotid gland and provide a reference for preoperative prediction of benign vs malignant status. STUDY DESIGN: Patients with parotid gland tumors treated surgically were selected. Relevant clinicopathological and imaging data were collected for patients with maximum tumor diameters ≤20 mm on preoperative computed tomography (CT). The lesions were divided into 2 groups, microtumors and minitumors, based on maximum tumor diameter. CT imaging features of benign and malignant tumors were compared through binary logistic regression analysis. RESULTS: Microtumors and minitumors were categorized by maximum diameters <10 mm (n = 74) and 10-20 mm (n = 611), respectively. Benign and malignant minitumors exhibited significant differences in boundary, tumor density, margin morphology, spiculation margin, and CT values in the plain and arterial phase (P ≤ .027), resembling those found in typical malignant parotid gland tumors. However, no significant differences were observed between benign and malignant microtumors. Logistic regression analysis identified boundary, margin morphology, and spiculation margin as independent predictors of malignancy. The prediction model excelled in identifying benign lesions but was less successful in identifying malignancies. CONCLUSION: Parotid gland minitumors had imaging features similar to typical larger malignant tumors. Active exclusion of the malignant risk and early surgical treatment is recommended for these tumors.
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Neoplasias de la Parótida , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , Diagnóstico Diferencial , Medios de Contraste , Anciano de 80 o más Años , AdolescenteRESUMEN
Rationale: Cisplatin-based chemotherapy is the first-line treatment for late-stage head and neck squamous cell carcinoma (HNSCC). However, resistance to cisplatin has become a major obstacle for effective therapy. Cancer stem cells (CSCs) are critical for tumor initiation, growth, metastasis, and chemoresistance. How to effectively eliminate CSCs and overcome chemoresistance remains a key challenge. Herein, we confirmed that MYC plays critical roles in chemoresistance, and explored targeting MYC to overcome cisplatin resistance in preclinical models. Methods: The roles of MYC in HNSCC cisplatin resistance and cancer stemness were tested in vitro and in vivo. The combined therapeutic efficiency of MYC targeting using the small molecule MYC inhibitor MYCi975 and cisplatin was assessed in a 4nitroquinoline 1-oxide-induced model and in a patient-derived xenograft model. Results: MYC was highly-expressed in cisplatin-resistant HNSCC. Targeting MYC using MYCi975 eliminated CSCs, prevented metastasis, and overcame cisplatin resistance. MYCi975 also induced tumor cell-intrinsic immune responses, and promoted CD8+ T cell infiltration. Mechanistically, MYCi975 induced the DNA damage response and activated the cGAS-STING-IRF3 signaling pathway to increase CD8+ T cell-recruiting chemokines. Conclusions: Our findings suggested that targeting MYC might eliminate CSCs, prevent metastasis, and activate antitumor immunity to overcome cisplatin resistance in HNSCC.
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Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/metabolismo , Resistencia a Antineoplásicos/genética , Neoplasias de Cabeza y Cuello/patología , Línea Celular Tumoral , Carcinoma de Células Escamosas/patología , Células Madre Neoplásicas/metabolismoRESUMEN
In 2009, a novel H1N1 influenza virus caused the first influenza pandemic of the 21st century. Studies have shown that the influenza M gene played important roles in the pathogenicity and transmissibility of the 2009 H1N1 pandemic ((H1N1)pdm09), whilst the underlying mechanism remains unclear. The influenza M gene encodes two proteins, matrix protein 1 and matrix protein 2, which play important roles in viral replication and assembly. In this study, it is found that the M2 protein of the (H1N1)pdm09 virus showed a lower mobility rate than the North America triple-reassortant influenza M2 protein in Polyacrylamide Gel Electrophoresis (PAGE). The site-directed mutations of the amino acids of (H1N1)pdm09 M2 revealed that E79 is responsible for the mobility rate change. Further animal studies showed that the (H1N1)pdm09 containing a single M2-E79K was significantly attenuated compared with the wild-type virus in mice and induced lower proinflammatory cytokines and IFNs in mouse lungs. Further in vitro studies indicated that this mutation also affected NLRP3 inflammasome activation. To reveal the reason why they have different mobility rates, a circular dichroism spectra assay was employed and showed that the two M2 proteins displayed different secondary structures. Overall, our findings suggest that M2 E79 is important for the virus replication and pathogenicity of (H1N1)pdm09 through NLRP3 inflammasome and proinflammatory response.
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Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Animales , Ratones , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Proteína con Dominio Pirina 3 de la Familia NLR , Virulencia , InflamasomasRESUMEN
The research aimed to study an Avian polyomavirus strain that was isolated in Shandong, China. To study the pathogenicity of APV in SPF chickens, and provide references for epidemiological research and disease prevention and control of APV. The genetic characterization of APV strain (termed APV-20) was analyzed and the pathogenicity of APV was investigated from two aspects: different age SPF chickens, and different infection doses. The results revealed that the APV-20 exhibits a nucleotide homology of 99% with the other three APV strains, and the evolution of APV In China was slow. In addition, the APV-20 infection in chickens caused depression, drowsiness, clustering, and fluffy feathers, but no deaths occurred in the infected chickens. The main manifestations of necropsy, and Hematoxylin and Eosin staining (HE) showed that one-day-old SPF chickens were the most susceptible, and there was a positive correlation between viral load and infection dose in the same tissue. This study showed that SPF chickens were susceptible to APV, and an experimental animal model was established. This study can provide a reference for the pathogenic mechanism of immune prevention and control of APV.
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Group-I Fowl adenovirus (FAdV) is still widespread in China's chicken farms, leading to huge economic losses. The traditional PCR method, which can detect all serotypes at the same time, is not sensitive enough to obtain accurate results, especially in some samples containing only a low titer of virus, such as contaminated live vaccine. In order to solve this problem, this study developed a dot blot assay based on the above PCR method. A total of 6 probes targeting the conserved region of FAdV were designed and systematically optimized through sensitivity, accuracy, and stability analyses. Results showed that it is not only suitable for 12 serotypes, but also effectively improve the sensitivity, which increased more than 100 times in comparison with PCR assay. Moreover, this sensitivity was increased 100 times when detecting contaminated live vaccine samples, showing the great prospect of this method in daily monitoring.
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Adenoviridae , Pollos , Animales , Reacción en Cadena de la Polimerasa/veterinariaRESUMEN
This retrospective case-series study aimed to elucidate the three-dimensional attachment morphometric features and to quantify the volumetric changes of the masticatory muscles following free fibular flap reconstruction of the mandibular condyle. Navigation software (iPlan, version 3.0; Brainlab) was used to perform delineation and volumetric measurement of the masticatory muscles using DICOM data. In total, 30 patients were included in this retrospective case series. In 25 cases (83.33%), the lateral pterygoid muscle achieved reattachment within 6 months postoperatively. The medial pterygoid muscles on the affected side achieved ectopic attachment in all cases. However, masseter reattachment on the affected side was achieved in only three cases. On the normal side, the volumes of lateral pterygoid muscle, medial pterygoid muscle, and masseter had recovered to almost preoperative levels at 1 year postoperatively. On the affected side, the volume of medial pterygoid muscle had decreased significantly (p = 2.4e-04) at 3 months postoperatively. The volumes of lateral pterygoid muscle and masseter showed mild decreases at 3 months postoperatively, but these were not significant (p = 0.52 and p = 0.05 for the pterygoid muscle and masseter, respectively). At 6 months after surgery, with the exception of the volume of the lateral pterygoid muscle (p = 0.06), the total volume of the masticatory muscles decreased significantly on the affected side. The volumes of lateral pterygoid muscle, medial pterygoid muscle, and masseter showed significant decreases at 1 year postoperatively (p = 0.03, p = 4.7e-08, and p = 1.1e-05, respectively) on the affected side. The postoperative volumes of the masseter, medial pterygoid, and lateral pterygoid muscles showed significant decreases due to the loss of reattachment. The results of this study may not help to ascertain whether reattachment of masticatory muscles will lead to better function. As a consequence, clinical trials of higher quality are needed.
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Cóndilo Mandibular , Músculos Masticadores , Humanos , Cóndilo Mandibular/diagnóstico por imagen , Cóndilo Mandibular/cirugía , Músculo Masetero/diagnóstico por imagen , Músculos Pterigoideos/diagnóstico por imagen , Músculos Pterigoideos/cirugía , Estudios RetrospectivosRESUMEN
MYC plays critical roles in tumorigenesis and is considered an attractive cancer therapeutic target. Small molecules that directly target MYC and are well tolerated in vivo represent invaluable anti-cancer therapeutic agents. Here, we aimed to investigate the therapeutic effect of MYC inhibitors in head and neck squamous cell carcinoma (HNSCC). The results showed that pharmacological and genetic inhibition of MYC inhibited HNSCC proliferation and migration. MYC inhibitor 975 (MYCi975), inhibited HNSCC growth in both cell line-derived xenograft and syngeneic murine models. MYC inhibition also induced tumor cell-intrinsic immune responses, and promoted CD8+ T cell infiltration. Mechanistically, MYC inhibition increased CD8+ T cell-recruiting chemokines by inducing the DNA damage related cGAS-STING pathway. High expression of MYC combined with a low level of infiltrated CD8+ T cell in HNSCC correlated with poor prognosis. These results suggested the potential of small-molecule MYC inhibitors as anti-cancer therapeutic agents in HNSCC.
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Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Humanos , Ratones , Nucleotidiltransferasas , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genéticaRESUMEN
Weaning transition generally impairs the immune system, inducing immune disturbance, which may be associated with post-weaning diarrhea and high mortality in piglets. The spleen is a pivotal lymphatic organ that plays a key role in the establishment of the immune system. Traditional Chinese medicine (TCM) prescriptions, XiaoJianZhong (XJZ) and Jiansananli-sepsis (JSS), are widely used prescriptions for treating spleen damage and diarrhea. Here, we hypothesized that XJZ and JSS maintain the spleen physiological function by ameliorating antioxidant capacity and inflammatory response in weaned piglets. In this study, 18 weaned piglets were assigned to the Control, XJZ and JSS groups. By hematoxylin and eosin staining, hematological analysis, flow cytometric analysis, qRT-PCR and western blot, the effects of both TCM prescriptions on the spleen antioxidant defense system and inflammatory pathway were explored. Results showed that both TCM treatment significantly ameliorated the weaning-induced morphological damage in piglets, as evidenced by clearer and more perfect spleen histology, as well as higher relative area of white pulp. Meanwhile, both XJZ and JSS exerted better blood parameters, as supported by the changes of monocyte level and lymphocyte subpopulations CD4+/CD8+ ratio. Furthermore, the levels of inflammatory markers, IL1ß, IL6, IL8, and TNF-α in the spleen were markedly decreased after supplemented with both TCM prescriptions. Importantly, the inhibition of nuclear factor-kappaB (NF-κB) and its downstream effector genes (IL6, IL8, and TNF-α) in both XJZ and JSS treatment groups further confirmed alleviation of inflammatory responses in the spleen. In addition, both XJZ and JSS enhanced the antioxidant capacity of the spleen by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)-activated antioxidant defense system. Notably, the results of PCA and network correlation analysis indicated that XJZ and JSS treatment altered the expression profiles of inflammatory and antioxidant-related factors in the spleen of weaned-piglets, which may involve the synergy of NF-κB and Nrf2 signaling pathways. In summary, our study showed that TCM prescriptions, XJZ and JSS could ameliorate inflammatory response and antioxidant capacity in the spleen by synergistically regulating NF-κB and Nrf2 signaling pathways in piglets.
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Chicken MDA5 (chMDA5), the essential accepted pattern recognition receptors for detecting cytoplasmic viral RNA in chicken, initiates interferon ß (IFN-ß) generation. However, there is an incomplete elucidation of regulating chMDA5-mediated IFN-ß production. NEMO-related protein, optineurin, was identified as inhibitors of virus triggered IFN-ß induction in human or mice. In this study, full length of chicken optineurin (chOPTN) was cloned from chicken embryo fibroblast, and its role in inhibiting IFN-ß signaling pathway was further explored. Full-length chOPTN encodes 547 amino acids residues and contains unique LC3 interaction region and ubiquitin binding domain. Chicken optineurin mRNA and protein are widely expressed in different tissues, especially the heart, kidney, and bursal fabricius (BF). Overexpressed chOPTN not only inhibits poly I:C or homos-induced human IFN-ß promoter activation in 293T cells but also suppresses poly I:C, infectious bursal disease virus (IBDV) genome double-strand RNA (dsRNA), and chMDA5-induced chicken IFN-ß (chIFN-ß) promoter activation. In addition, we first revealed that chOPTN negatively regulates chIFN-ß production via inhibiting ubiquitination of chicken TBK1, which is dependent on the ubiquitin-binding domain of chOPTN. Moreover, chIFN-ß stimulus, poly I:C, and IBDV genome dsRNA improve chOPTN expression. Endogenous chOPTN expression is also upregulated by IBDV infection in 293T, DF-1 cells, as well as in BF. Therefore, our results suggested that chOPTN plays an inhibition role of chMDA5-mediated chIFN-ß signaling pathway in chicken cells.
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Proteínas de Ciclo Celular , Pollos , Regulación de la Expresión Génica , Helicasa Inducida por Interferón IFIH1 , Animales , Infecciones por Birnaviridae/inmunología , Infecciones por Birnaviridae/veterinaria , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Embrión de Pollo , Pollos/genética , Pollos/inmunología , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/inmunología , Virus de la Enfermedad Infecciosa de la Bolsa/fisiología , Helicasa Inducida por Interferón IFIH1/inmunología , Interferón beta/genética , ARN Bicatenario/genéticaRESUMEN
Cadmium (Cd) is a harmful heavy metal that can cause many health problems, while selenium (Se) is an essential nutrient for organisms that can protect them from heavy metal-induced damage. To explore the effects of Se on Cd-induced mitophagy in the liver, forty 3-month-old New Zealand white rabbits (2-2.5 kg), half male and half female, were randomly divided into four groups: the Control group, the Se (0.5 mg/kg body weight (BW)) group, the Cd (1 mg/kg BW) group and the Se+Cd group. After 30 days, the toxicity from Cd in the liver was assessed in terms of the nuclear xenobiotic receptor (NXR) response, oxidative stress and mitophagy. It was found that Cd decreased the activities of CYP450 enzymes and antioxidant enzymes and increased the contents of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and also increased the consumption of reduced glutathione (GSH). Moreover, the mRNA levels of NXRs (CAR, PXR, AHR and Nrf2), some mitochondrial function factors (PGC-1α, Sirt1, Sirt3, Nrf1 and TFAM) and mitochondrial fusion factors (Mfn1, Mfn2 and OPA1) were downregulated, but the mRNA levels of other mitochondrial function factors (VDAC1, Cyt C and PRDX3), mitochondrial fission factors (Fis1 and MFF) and those in the PINK1/Parkin-mediated mitophagy pathway (p62, Bnip3 and LC3) were upregulated under Cd exposure. The protein expression levels of Nrf2, SOD2, PGC-1α, PINK1 and Parkin were consistent with the mRNA expression levels in the Cd group. Se alleviated the changes in the abovementioned factors induced by Cd. In conclusion, the results indicate that Cd can cause oxidative stress in rabbit livers by inhibiting NXRs and the antioxidation response leading to mitophagy, and these harmful changes caused by Cd can be alleviated by Se.
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Cadmio , Selenio , Animales , Cadmio/metabolismo , Cadmio/toxicidad , Femenino , Peróxido de Hidrógeno/metabolismo , Hígado/metabolismo , Masculino , Mitofagia , Estrés Oxidativo , Conejos , Selenio/metabolismo , Xenobióticos/metabolismoRESUMEN
Avian leukosis (AL) is one of the most pandemic immunosuppressive diseases and has been widely spread between 2006 and 2009 in China. The contamination of avian leukosis virus (ALV) in attenuated vaccine is considered as one of the possible transmission routes of this disease. Based on a retrospective survey of 918 batches of attenuated vaccine produced before 2010, three of them were identified as ALV-positive and corresponding ALV strains were successfully isolated from a live Fowlpox virus vaccine, a live Newcastle disease virus vaccine and a live Infectious Bursal Disease virus vaccine, respectively, and whole-genome sequencing showed that these three isolates shared the highest homology with ALV-A wild strains isolated in China (97.7%) over the same period, and the phylogenetic analysis based on their gp85 genes further confirmed that they belong to subgroup A. Meanwhile, although these three ALV-A strains isolated from contaminated vaccines shared a close genetic relationship, their U3 region of genome have a relatively low identity, suggesting that these three strains may have different sources. This study reminds us once again that the possibility of ALV infecting chickens through contaminated live vaccines, requiring us to carry out stricter exogenous virus monitoring in vaccines.
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Virus de la Leucosis Aviar/genética , Virus de la Leucosis Aviar/aislamiento & purificación , Vacunas Virales/normas , Animales , Leucosis Aviar/prevención & control , Pollos , China , Filogenia , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/virología , Estudios Retrospectivos , Análisis de Secuencia de ADN , Vacunas Atenuadas/normas , Secuenciación Completa del GenomaRESUMEN
Diarrhea is a leading cause of death in piglets. XiaoJianZhong (XJZ) and Jingsananli-sepsis (JSS) were two traditional Chinese medicine (TCM) prescriptions to prevent and treat intestinal diseases, including diarrhea and inflammatory disease. Here, we investigated the effects of XJZ and JSS on diarrhea rate, growth performance, colonic inflammation, and caecum microbiota in piglets. A total of 18 piglets were selected and randomly divided into three groups. Control group was supplied with basal diets, while TCM1 and TCM2 groups were, respectively, supplied with XJZ and JSS in basal diets. Decreased diarrhea rate, colonic or caecal pH, and elevated apparent nutrient digestibility were observed in both TCM groups. Meanwhile, both prescriptions alleviated colonic inflammation by decreasing mRNA expression of proinflammatory cytokines and suppressing the TLR4/MyD88/NF-κB signaling pathway. Additionally, TCM1 and TCM2 prescriptions ameliorated caecum microbiota composition and increased the abundance of beneficial bacteria, together with regulations on several genes that are responsible for signaling pathways involved in cancers and metabolic diseases. Importantly, both TCM1 and TCM2 significantly promoted the average daily gain (ADG) and reduced the feed : gain (F : G) ratio. In conclusion, both TCM prescriptions effectively decreased diarrhea rate and increased growth performance by elevating apparent nutrient digestibility and gut health, via relieving colonic inflammation and ameliorating gut microbiota composition of piglets.
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The purpose of this study was to evaluate the effects of excessive molybdenum (Mo) on renal function and oxidative stress in goats. Twenty-seven healthy goats were randomly allotted in three groups and were fed deionized water to which sodium molybdate [(NH4)6Mo7O24·4H2O] was added at different doses of 0, 15, and 45 mg Mo/(kg·BW) for 50 days, respectively. The results indicated that white blood cell (WBC) counts were significantly increased (P < 0.05), while red blood cell (RBC) counts, hemoglobin (HGB), and mean corpuscular hemoglobin concentration (MCH) were tended to decrease with the increasing of the experimental period in high-Mo group compared with the control group. Besides, blood urea nitrogen (BUN) and creatinine (CREA) contents in serum were increased (P < 0.05) in both groups supplemented with molybdenum. Meanwhile, contents of copper (Cu) from the both experimental groups were significantly decreased (P < 0.05), while contents of zinc (Zn) and iron (Fe) were increased (P < 0.05) in serum. The contents of Cu were significantly increased (P < 0.05), while the contents of zinc (Zn) and iron (Fe) did not obviously change (P > 0.05) in the kidney. In addition, the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased (P < 0.05) in the mitochondria, whereas malondialdehyde (MDA) and nitric oxide synthase (NOS) expression significantly increased (P < 0.05). Collectively, these results indicated that excess Mo exposure could induce secondary Cu deficiency and oxidative stress in the kidney, which finally undermine the renal function of goats.
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Cabras , Molibdeno , Animales , Antioxidantes , Riñón , Mitocondrias , Molibdeno/toxicidad , Estrés OxidativoRESUMEN
Infectious bursal disease (IBD) is a highly infectious disease in chicken, and vaccination is the best way to prevent outbreak of infectious bursal disease virus (IBDV). In this study, we isolated a variant IBDV strain from a chicken farm with vaccinated chickens. The full genome of this IBDV strain was determined and analyzed.
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Psittacine beak and feather disease virus (PBFDV) has been reported in many countries, such as Australia, Poland, the United States, South Africa, etc. In this study, the complete genome of a PBFDV isolate was determined and characterized from budgerigars in China.
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Research on the role of trait emotional intelligence (trait EI; Petrides, 2001) relating to teaching performance has emerged as an important topic. The present study proposes a multilevel model of teachers' trait EI in relation to their job performance, which simultaneously addresses the mediating role of job satisfaction and the influences of school-level factors (i.e., organizational trust and principals' trait EI). Results from a sample of 881 teachers and 37 principals in Chinese primary schools showed that job satisfaction partially mediated the positive relationship between teachers' trait EI and their job performance. In addition, the findings demonstrated a cross-level moderated mediating effect, with the indirect effect of teachers' trait EI on job performance (via job satisfaction) becoming stronger for teachers working in schools with lower levels of organizational trust. The hypothesized role of principals' trait EI on teachers' job performance was not supported. The theoretical and practical implications of these findings are discussed.