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Porcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory disease in pigs of all ages and reproductive failure in sows, resulting in great economic losses to the swine industry. In this work, we identified the interaction between PSMB4 and PRRSV Nsp1α by yeast two-hybrid screening. The PSMB4-Nsp1α interaction was further confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown, and laser confocal experiments. The PCPα domain (amino acids 66 to 166) of Nsp1α and the C-terminal domain (amino acids 250 to 264) of PSMB4 were shown to be critical for the PSMB4-Nsp1α interaction. PSMB4 overexpression reduced PRRSV replication, whereas PSMB4 knockdown elicited opposing effects. Mechanistically, PSMB4 targeted K169 in Nsp1α for K63-linked ubiquitination and targeted Nsp1α for autolysosomal degradation by interacting with LC3 to enhance the activation of the lysosomal pathway. Meanwhile, we found that PSMB4 activated the NF-κB signaling pathway to produce type I interferons by downregulating the expression of IκBα and p-IκBα. In conclusion, our data revealed a new mechanism of PSMB4-mediated restriction of PRRSV replication, whereby PSMB4 was found to induce Nsp1α degradation and type I interferon expression, in order to impede the replication of PRRSV. IMPORTANCE In the swine industry, PRRSV is a continuous threat, and the current vaccines are not effective enough to block it. This study determined that PSMB4 plays an antiviral role against PRRSV. PSMB4 was found to interact with PRRSV Nsp1α, mediate K63-linked ubiquitination of Nsp1α at K169, and thus trigger its degradation via the lysosomal pathway. Additionally, PSMB4 activated the NF-κB signaling pathway to produce type I interferons by downregulating the expression of IκBα and p-IκBα. This study extends our understanding of the proteasome subunit PSMB4 against PRRSV replication and will contribute to the development of new antiviral strategies.
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Interferon Tipo I , Vírus da Síndrome Respiratória e Reprodutiva Suína , Complexo de Endopeptidases do Proteassoma , Proteínas não Estruturais Virais , Expressão Gênica/imunologia , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interferon beta/genética , Lisossomos/metabolismo , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/imunologia , Domínios Proteicos , Proteólise , Suínos , Ubiquitinação , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/genética , AnimaisRESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) is a viral pathogen with substantial economic implications for the global swine industry. The existing vaccination strategies and antiviral drugs offer limited protection. Replication of the viral RNA genome encompasses a complex series of steps, wherein a replication complex is assembled from various components derived from both viral and cellular sources, as well as from the viral genomic RNA template. In this study, we found that ZNF283, a Krüppel-associated box (KRAB) containing zinc finger protein, was upregulated in PRRSV-infected Marc-145 cells and porcine alveolar macrophages and that ZNF283 inhibited PRRSV replication and RNA synthesis. We also found that ZNF283 interacts with the viral proteins Nsp9, an RNA-dependent RNA polymerase, and Nsp10, a helicase. The main regions involved in the interaction between ZNF283 and Nsp9 were determined to be the KRAB domain of ZNF283 and amino acids 178-449 of Nsp9. The KRAB domain of ZNF283 plays a role in facilitating Nsp10 binding. In addition, ZNF283 may have an affinity for the 3' untranslated region of PRRSV. These findings suggest that ZNF283 is an antiviral factor that inhibits PRRSV infection and extend our understanding of the interactions between KRAB-containing zinc finger proteins and viruses.
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Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Doenças dos Suínos , Animais , Suínos , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Ligação Proteica , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , RNA Viral/metabolismo , Dedos de Zinco , Replicação ViralRESUMO
OBJECTIVE: To investigate the reliability and validity of the Chinese version of simplified nutritional appetite questionnaire (SNAQ). METHODS: The SNAQ was translated and back-translated for the study population. We surveyed 122 community-dwelling residents aged ≥60 years in Beijing's residential communities. Participants underwent face-to-face surveys including the SNAQ, mini-nutritional assessment short-form (MNA-SF), FRAIL scale, Sarcopenia-Five (SCAR-F), 15-item Geriatric Depression Scale (GDS-15), 7-item Generalized Anxiety Disorder (GAD-7), 8-item Oral Frailty Index (OFI-8), 10-item Eating Assessment Tool (EAT-10), and Mini-Mental State Examination (MMSE). Cronbach's alpha was used to measure the internal consistency and the relationship between individual items. The construct validity was verified using the KMO-Bartlett. Concurrent validity was established to validate measures of the same constructs. RESULTS: Cronbach's alpha measured the internal consistency of the questionnaire at 0.694. The split-half reliability stood at 0.725. The construct validity of the SNAQ was confirmed using a KMO-Bartlett value of 0.648 (P <0.001). The MNA-SF, as validation benchmark, has a correlation coefficient of 0.345 (P =0.001). CONCLUSION: The Chinese version of the SNAQ has good reliability and validity for older adults in community settings.
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In fish, skin mucus forms a protective barrier between the body surface and the external water environment, thus providing the most direct and intuitive clues to monitor the subject's health condition. To explore the impact of the Vibrio harveyi pathogen on teleost, the proteome of epidermal mucus from control and sick Cynoglossus semilaevis were screened through iTRAQ followed with LC-MS/MS. 1531 credible proteins were obtained relating to structural, metabolic and immunological functions. 335 different expressed proteins (DEPs) were identified, with 166 up-regulated and 169 down-regulated in MS. 62 proteins were characterized, including 22 up-regulated proteins and 40 down-regulated proteins. Integrated analysis of DE-miRNAs and DEPs from miRomics and proteomics were conducted to show the indirect regulatory relationship. Comparative analysis of DEPs between mucus and exosomes demonstrated that exosomes contributed the most DEPs of all mucus DEPs. 125 proteins are DEPs only in exosomes, which presented minor difference in total mucus. Expression of Aminopeptidase (anpep), Calcium-transporting ATPase, Histone H2B and H2A confirmed implied fine discriminative power with infected C. semilaevis, among which Calcium-transporting ATPase and H2B also appeared in list of exosomal markers. This study might shed the light on effective biomarker digging at other extended screening scenarios.
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Exossomos , Animais , Proteômica , Cromatografia Líquida , Estudos de Viabilidade , Espectrometria de Massas em Tandem , Muco/metabolismo , ProteomaRESUMO
Restoring immune balance by targeting macrophage polarization is a potentially valuable therapeutic strategy for ulcerative colitis (UC). Dioscin is a steroidal saponin with potent anti-inflammatory, immunoregulatory, and hypolipidemic effects. This study examined the protective effect of Dioscin on UC in mice and explored the underlying mechanisms. Mice were induced colitis by dextran sulfate sodium (DSS) and concurrently treated with Dioscin oral administration. RAW264.7 cells were skewed to M1 macrophage polarization by lipopolysaccharide (LPS) and interferon-γ (INF-γ) in vitro, and received Dioscin treatment. The results showed that Dioscin ameliorated colitis in mice, reduced macrophage M1 polarization, but markedly promoted M2 polarization in mice colon. Dioscin inhibited mammalian target rapamycin complex 1 (mTORC1)/hypoxia-inducible factor-1α (HIF-1α) signaling and restrained glycolysis in RAW264.7; however, it activated mammalian target rapamycin complex 2 (mTORC2)/peroxisome proliferator-activated receptor-γ (PPAR-γ) signal and facilitated fatty acid oxidation (FAO). The modulation of mTORs signaling may inhibit M1, but promote M2 polarization. Furthermore, the effect of Dioscin on M2 polarization was neutralized by the FAO inhibitor Etomoxir and the mTORC2 inhibitor JR-AB2-011. In parallel, the inhibitory effect of Dioscin on M1 polarization was mitigated by the mTORC1 agonist L-leucine. Both JR-AB2-011 and L-leucine blocked the therapeutic effect of Dioscin in mice with UC. Therefore, Dioscin ameliorated UC in mice, possibly by restraining M1, while skewing M2 polarization of macrophages. Regulation of mTORC1/HIF-1α and mTORC2/PPAR-γ signals is a possible mechanism by which Dioscin inhibited aerobic glycolysis and promoted FAO of macrophages. In summary, Dioscin protected mice against DSS-induced UC by regulating mTOR signaling, thereby adjusting macrophage metabolism and polarization.
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Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Diosgenina/análogos & derivados , Macrófagos/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Citocinas/genética , Sulfato de Dextrana , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Modelos Animais de Doenças , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/imunologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , PPAR gama/metabolismo , Células RAW 264.7RESUMO
Immune cells infiltrating the psoriatic skin secrete high amounts of pro-inflammatory cytokines IL-17, TNF-α, IL-21 and IL-36 resulting in chronic inflammation. However, the exact cellular and molecular mechanisms have not been fully understood. We report here elevation of IL-33 expression in psoriatic lesions. Studies in imiquimod (IMQ)-induced mice with psoriatic inflammation confirmed a critical role for IL-33 in driving the disease. IL-33 reduces the CD4+ and CD8+ cells, inhibits autophagy in IMQ-treated mouse skin, and promoted tyrosyl phosphorylation of STAT3. Thus, IL-33 appears to be a major risk factor for severity of psoriasis-like skin inflammation. Our findings may open new perspectives for understanding the mechanisms and developing a therapeutic strategy for psoriasis.
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Interleucina-33/metabolismo , Psoríase/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imiquimode/uso terapêutico , Inflamação/metabolismo , Interleucina-17/metabolismo , Interleucinas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Psoríase/induzido quimicamente , Fator de Transcrição STAT3/metabolismo , Pele/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The BES1 gene family, an important class of plant-specific transcription factors, play key roles in the BR signal pathway in plants, regulating various development processes. Until now, there has been no comprehensive analysis of the BES1 gene family in Brassica napus, and a cross-genome exploration of their origin, copy number changes, and functional innovation in plants was also not available. RESULTS: We identified 28 BES1 genes in B. napus from its two subgenomes (AA and CC). We found that 71.43% of them were duplicated in the tetraploidization, and their gene expression showed a prominent subgenome bias in the roots. Additionally, we identified 104 BES1 genes in another 18 representative angiosperms and performed a comparative analysis with B. napus, including evolutionary trajectory, gene duplication, positive selection, and expression pattern. Exploiting the available genome datasets, we performed a large-scale analysis across plants and algae suggested that the BES1 gene family could have originated from group F, expanding to form other groups (A to E) by duplicating or alternatively deleting some domains. We detected an additional domain containing M4 to M8 in exclusively groups F1 and F2. We found evidence that whole-genome duplication (WGD) contributed the most to the expansion of this gene family among examined dicots, while dispersed duplication contributed the most to expansion in certain monocots. Moreover, we inferred that positive selection might have occurred on major phylogenetic nodes during the evolution of plants. CONCLUSIONS: Grossly, a cross-genome comparative analysis of the BES1 genes in B. napus and other species sheds light on understanding its copy number expansion, natural selection, and functional innovation.
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Brassica napus/classificação , Brassica napus/genética , Evolução Molecular , Genes de Plantas , Genoma de Planta , Família Multigênica , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Mapeamento Cromossômico , Cromossomos de Plantas , Duplicação Gênica , FilogeniaRESUMO
A new, efficient, and atom-economic visible-light-promoted radical acylation/cyclization of alkynoates with aldehydes was developed for the synthesis of 3-acylcoumarins. The reaction undergoes a domino radical addition/5-exo cyclization, and ester migration to afford the product in moderate to good yields with wide functional group tolerance. The significant feature of this new method is the excellent tolerance of aliphatic aldehydes, which leads to the efficient synthesis of aliphatic 3-acylcoumarins.
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Pd-Catalyzed o-C-H functionalization of α-phenylglycine, 4-hydroxyphenylglycine and phenylalanine using picolinamide as a directing group is reported. We have developed different protocols for the arylation, alkylation, alkynylation, halogenation, alkoxylation, and acyloxylation of these amino acids. The reactions exhibit high selectivity, broad substrate scope, and compatibility with different functional groups in moderate to high yields. They provide a rapid and efficient access to a variety of phenyl based amino acid derivatives which can be further modified and have broad spectrum of applications in medicinal chemistry.
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According to the World Health Organization,palliative care is an approach that prevents and alleviates the pain of patients with life-threatening illness and improves the quality of life of patients and their families through early identification,assessment and treatment of pain and other physical,psychosocial and spiritual problems. It is the active holistic care accomplished by multidisciplinary team. This article describes the practice of the palliative care in a patient with advanced retroperitoneal sarcoma.
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Cuidados Paliativos , Qualidade de Vida , Assistência Terminal , Humanos , Dor/prevenção & controle , Sarcoma/terapiaRESUMO
Africa swine fever (ASF) is a highly pathogenic contagion caused by African swine fever virus (ASFV), which not only affects the development of domestic pig industry, but also causes huge losses to the world agricultural economy. Vaccine development targeting ASFV remains elusive, which leads to severe difficulties in disease prevention and control. Emodin (EM) and rhapontigenin (RHAG), which are extracted from the dried rhizome of Polygonum knotweed, have various biological properties such as anti-neoplastic and anti-bacterial activities, but no studies have reported that they have anti-ASFV effects. This study discovered that EM and RHAG at different concentrations had a significant dose-dependent inhibitory effect on the ASFV GZ201801 strain in porcine alveolar macrophages (PAMs), and at the specified concentration, EM and RHAG showed continuous inhibition at 24 h, 48 h and 72 h. Not only did they strongly impact virion attachment and internalization, but also inhibit the early stages of ASFV replication. Further research proved that the expression level of Rab 7 protein was reduced by EM and RHAG, and treatments with EM and RHAG induced the accumulation of free cholesterol in endosomes and inhibited endosomal acidification, which prevented the virus from escaping and shelling from late endosomes. This study summarized the application of EM and RHAG in inhibiting ASFV replication in-vitro. Similarly, EM and RHAG targeted Rab 7 in the viral endocytosis pathway, inhibited viral infection, and induced the accumulation of cholesterol in the endosomes and the acidification of the endosomes to inhibit uncoating. A reference could be made to the results of this study when developing antiviral drugs and vaccines.
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Vírus da Febre Suína Africana , Febre Suína Africana , Emodina , Doenças dos Suínos , Suínos , Animais , Vírus da Febre Suína Africana/fisiologia , Internalização do Vírus , Emodina/metabolismo , Emodina/farmacologia , Sus scrofa , Colesterol/metabolismo , Replicação ViralRESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus belonging to the Arteriviridae family. Currently, the strain has undergone numerous mutations, bringing massive losses to the swine industry worldwide. Despite several studies had been conducted on PRRSV, the molecular mechanisms by which it causes infection remain unclear. Proliferating cell nuclear antigen (PCNA) is a sign of DNA damage and it participates in DNA replication and repair. Therefore, in this study, we investigated the potential role of PCNA in PRRSV infection. We observed that PCNA expression was stable after PRRSV infection in vitro; however, PCNA was translocated from the nucleus to the cytoplasm. Notably, we found the redistribution of PCNA from the nucleus to the cytoplasm in cells transfected with the N protein. PCNA silencing inhibited PRRSV replication and the synthesis of PRRSV shorter subgenomic RNA (sgmRNA) and genomic RNA (gRNA), while PCNA overexpression promoted virus replication and PRRSV shorter sgmRNA and gRNA synthesis. By performing immunoprecipitation and immunofluorescence colocalization, we confirmed that PCNA interacted with replication-related proteins, namely NSP9, NSP12, and N, but not with NSP10 and NSP11. Domain III of the N protein (41-72 aa) interacted with the IDCL domain of PCNA (118-135 aa). Therefore, we propose cytoplasmic transport of PCNA and its subsequent influence on PRRSV RNA synthesis could be a viral strategy for manipulating cell function, thus PCNA is a potential target to prevent and control PRRSV infection.
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Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Doenças dos Suínos , Animais , Genoma Viral , Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , RNA , Suínos , Doenças dos Suínos/genética , Proteínas não Estruturais Virais/genética , Replicação Viral/genética , RNA Subgenômico/genéticaRESUMO
Dysregulated immune response plays a pivotal role in Ulcerative colitis. In lamina propria of inflammatory colonic mucosa, macrophages tend to polarize into M1 type and metabolically reprogram to aerobic glycolysis. PKM2 orchestrates glucose metabolic switch in macrophages, which tetramer has high pyruvate kinase activity, while which dimer mainly works as a protein kinase to stabilize HIF-1α and mediate anabolism. Shikonin is a potent PKM2 inhibitor derived from traditional Chinese medicine Arnebiae Radix with anti-inflammatory and anticarcinogen activities. However, it is unclear which conformation of PKM2 is inhibited by Shikonin, and whether this inhibition mediates pharmacological effect of Shikonin. In this study, we examined the efficacy of Shikonin on dextran sulfate sodium-induced mice colitis and determined the states of PKM2 aggregation after Shikonin treatment. Results showed that Shikonin dose-dependently alleviated mice colitis, down-regulated expression of F4/80, iNOS and CD86, decreased IFN-γ, IL-1ß, IL-6 and TNF-α, while increased IL-10 in mice colon. Furthermore, Shikonin suppressed the pyruvate, lactate production and glucose consumption, inhibited the pyruvate kinase activity and nuclear translocation of PKM2, and decreased both dimerization and tetramerization of PKM2 in macrophages. In vitro assay revealed that Shikonin bounded to PKM2 protein, inhibited the formation of both dimer and tetramer, while promoted aggregation of PKM2 macromolecular polymer. TEPP-46, an activator of PKM2 tetramerization, attenuated the ameliorative effect of Shikonin on disuccinimidyl suberate mice. In summary, Shikonin improved mice colitis, which mechanism may be mediated by inhibiting dimerization and tetramerization of PKM2, suppressing aerobic glycolysis reprogram, improving mitochondrial dynamic, and therefore alleviating inflammatory response of macrophages.
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BACKGROUND: Stroke survivors and their caregivers experience different difficulties that arise from certain physical, psychological, social aspects and caring burdens during the hospital-to-home transitional period. Although there are abundant studies that focus on stroke transitional care, there are limited qualitative studies that synthesize the experience of hospital-to-home transitional care for stroke survivors and their caregivers in China. OBJECTIVE: To evaluate the experience of stroke survivors and their family caregivers during hospital-to-home transitional care in China. METHODS: A qualitative longitudinal study based on semi-structured interviews were implemented to address the research objective. Interviews were conducted at two stages, (1) when stroke survivors were close to discharge, and (2) within two months post-discharge. Participants were recruited from one tertiary hospital between April and September 2019. Data were analyzed using reflexive thematic analysis. FINDINGS: Twenty-three stroke survivor/caregiver dyads participated, totaling 92 individual interviews. The thematic framework based on the experience of stroke survivors and caregivers reveals a three-phases of the hospital-to-home trajectory: survived, living in the mist, and crisis at home. The study identified one key theme (the optimism and hope) in the first phase, four key themes in the second (the pre-discharge emotional concerns and reactions, lack of stroke knowledge and stroke care information, difficulties of performing home-based healthcare, expectation of hospital pre-discharge) and in the third phase (high level of post-discharge stress, inaccessible postdischarge care services and health resources, interpersonal relationship disruption and lifestyle changes, financial burdens) respectively. In addition, several interconnected subthemes for stroke survivors' and caregivers' experiences were identified in each phase. CONCLUSION: The experience of stroke survivors and caregivers during hospital-to-home transitional care is a dynamic process with enormous challenges in each phase. These findings have implications for policymakers and health care systems regarding developing an enabling environment that supports successful hospital-to-home transitional care. Collaboration with health care professionals, accessible rehabilitation services and follow-up support after discharge, and available community and social support are warranted to be integrated into transitional care to help stroke survivors and caregivers to facilitate their hospital-to-home trajectory.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Cuidado Transicional , Assistência ao Convalescente , Cuidadores/psicologia , Hospitais , Humanos , Estudos Longitudinais , Alta do Paciente , Pesquisa Qualitativa , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/terapia , Sobreviventes/psicologiaRESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses the innate immune response in the host, reducing and delaying neutralizing antibody production against PRRSV infection and promoting viral infection. Here, we aimed to assess the potential of Panax notoginseng saponins (PNS) for improving the immune response exerted upon PRRSV-2-modified live virus (MLV) vaccine administration. Thirty piglets were randomly divided into six groups. Group 1 piglets were injected with medium 0 days post vaccination (dpv). Group 2 piglets were fed PNS 0-28 dpv. Group 3 and group 4 piglets were administered the JXA1-R vaccine 0 dpv. Group 4 piglets were also fed PNS 0-28 dpv. Group 1-4 piglets were challenged intranasally with the PRRSV JXA1 strain 28 dpv. Group 5 piglets were fed with PNS without challenge. Group 6 piglets served as controls. During the experiment, the samples were collected regularly for 49 days. Compared with group 1 piglets, group 3 piglets showed significantly reduced viremia and clinical scores, and significantly increased average daily gain (ADWG). Compared with group 3 piglets, group 4 piglets showed significantly improved neutralizing antibody titers, IFN-α and IFN-ß mRNA expression, and significantly decreased viremia and viral load in the lungs and lymph nodes, but did not demonstrate any further improvement in PRRSV-specific antibody titer, rectal temperature, ADWG, or clinical scores. PNS upregulates neutralizing antibodies against PRRSV-2 and enhances the expression of IFN-α and IFN-ß, which may reduce PRRSV viremia upon PRRSV-2 MLV vaccine administration. PNS may serve as an effective immunomodulator for boosting the immune defense against PRRSV.
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BACKGROUND: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. METHODS: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. RESULTS: A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. CONCLUSIONS: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.
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Doença de Alzheimer , Preparações Farmacêuticas , Atividades Cotidianas , Doença de Alzheimer/tratamento farmacológico , China , Inibidores da Colinesterase , Método Duplo-Cego , Humanos , Manose/análogos & derivados , Oligossacarídeos , Sódio , Resultado do TratamentoRESUMO
AIM: Few studies have comprehensively evaluated the factors associated with health-related quality of life (HRQOL) in the elderly. The purpose of the study is to identify the factors associated with HRQOL using a comprehensive geriatric assessment of community-dwelling elderly people in Beijing, China. METHODS: A cross-sectional survey of 896 community-dwelling elderly people in Beijing was conducted through face-to-face interviews. Data regarding sociodemographic factors, chronic disease (assessed by the Cumulative Illness Rating Scale for Geriatrics, CIRS-G), common geriatric syndromes and HRQOL (assessed by the EuroQol 5-Dimension questionnaire, EQ-5D) were collected using a structured questionnaire. Binary logistic regression analysis was used to identify the factors related to HRQOL. RESULTS: The CIRS-G comorbidity index was negatively related to the EQ-5D index and EQ-Visual Analog Scale (VAS) (P < 0.05). Geriatric syndromes such as chronic pain and non-optimal nutrition were negatively related to HRQOL (P < 0.05), and the negative influence of geriatric syndromes on the EQ-5D index was stronger than that of the cumulative comorbidities. Functional status in daily living activities was positively related to HRQOL (P < 0.05). Receiving care from children was positively related to EQ-VAS (P < 0.05). CONCLUSIONS: Besides cumulative comorbidities and geriatric syndromes, in particular nutritional problems and chronic pain exert a substantial negative impact on the HRQOL of elderly people in China, whereas family support is an important protective factor. Geriatr Gerontol Int 2020; 20: 422-429.
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Avaliação Geriátrica , Qualidade de Vida , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , China , Doença Crônica/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Vida Independente , Masculino , Estado Nutricional , Inquéritos e QuestionáriosAssuntos
Astrócitos/imunologia , Doenças Autoimunes do Sistema Nervoso/diagnóstico por imagem , Doenças Autoimunes do Sistema Nervoso/imunologia , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/imunologia , Proteína Glial Fibrilar Ácida/imunologia , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Gastroenteropatias/tratamento farmacológico , Glucocorticoides/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
BACKGROUND: Although Parkinson's disease (PD) is clinically characterized by motor symptoms, cognitive impairment is one of the most disabling non-motor symptoms. Despite it attracting increasing attention worldwide, less is known about its prevalence in the Chinese population. The objective of this study was to assess cognitive impairment and related risk factors in Chinese PD patients. METHODS: We collected the demographic, diagnostic, and treatment information of 901 PD patients from 42 centers throughout the People's Republic of China, then administered a battery of neuropsychological tests, to assess motor, cognitive, and neuropsychiatric symptoms. RESULTS: Overall, 193 of 901 (21.4%) PD patients met the criteria for dementia (PD-D), and 206 (22.8%) met the criteria for mild cognitive impairment (PD-MCI). Visuospatial dysfunction and attention/executive impairment predominated. Increased severity of cognitive impairment was associated with greater motor impairment. Patients with psychiatric symptoms, such as depression and hallucinations, were more likely to have dementia. Potentially, the younger-aged and more educated are shown less cognitive impairment, but age at onset, and levodopa equivalent dose, were not associated with the presence of cognitive dysfunction. CONCLUSION: The prevalence and profile of cognitive impairment in Chinese PD patients, as well as the risk factors, are similar as those reported for other races, but the frequency of nonamnestic cognitive domains differs.