Dual antiplatelet therapy after intravenous thrombolysis for patients with minor ischemic stroke：A meta-analysis.

OBJECTIVE: Intravenous thrombolysis (IVT) has been shown to effectively decrease both the disability rate and mortality associated with acute ischemic stroke, however, there is also a risk of vascular re-occlusion. Antiplatelet therapy can mitigate this risk. Nevertheless, there are no relevant guidelines recommending whether the administration of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel can be performed following thrombolysis. The aim of this study was to conduct a meta-analysis utilizing multiple studies in order to assess the effectiveness and safety of DAPT after IVT in cases of acute mild ischemic stroke (AMIS). METHODS: A comprehensive search on English literature published was performed on databases including PubMed, Embase, Web of Science, and Cochrane up until September 1, 2023. All cases were ischemic stroke patients who underwent IVT within a 4.5-hour timeframe and had a National Institutes of Health Stroke Scale (NIHSS) score of ≤5 (or 3) upon admission. The primary efficacy endpoint is the 90-day Modified Rankin Scale (mRS) Score (MRS score 0-1), while the primary safety endpoint encompassed the occurrence of symptomatic intracranial hemorrhage (SICH) and 90-day mortality. The study's secondary objective is the recurrence of any type of stroke (hemorrhagic and ischemic) within a 90-day period. The included studies underwent an evaluation of bias risk using the Newcastle Ottawa scale. Risk ratios (RRs) and CIs were calculated using a random effects model, and the findings and heterogeneity among the included studies were visually presented on a forest plot. (There was a protocol registration (PROSPERO):). RESULTS: Out of the 1081 studies that were obtained, only 3 met the criteria and were included in the meta-analysis (657 patients in total). The findings indicate that, there was a significant difference in the mRS of 0-1 between single antiplatelet therapy (SAPT) with only aspirin or clopidogrel and DAPT with aspirin and clopidogrel ((RR,1.11[95%CI,0.99-1.24];P=0.07;I2=55%), and no significant difference in stroke recurrence after 90 days or 1 year ((RR,0.94[95%CI,0.41-2.16];P=0.89;I2=30%); Regarding safety evaluation, the results showed no significant difference in the SICH (RR,0.65[95%CI,0.11-3.97];P=0.64;I2=0%) and the incidence of mortality (RR,0.97[95%CI,0.19-4.96];P=0.97;I2=0%) between the two groups. CONCLUSIONS: For patients with acute mild ischemic stroke (AMIS), in conjunction with DAPT after IVT can improve the 90-day prognosis, without increasing the risk of intracranial hemorrhage and 90-day mortality. However, it cannot reduce the risk of stroke recurrence.

The Clinical Relevance and Functional Implications of Thymosin Beta-10 in Glioma.

Glioma is a highly aggressive form of brain cancer characterized by limited treatment options and poor patient prognosis. In this study, we aimed to elucidate the oncogenic role of thymosin beta-10 (TMSB10) in glioma through comprehensive analyses of patient data from the TCGA and GTEx databases. Our investigation encompassed several key aspects, including the analysis of patients' clinical characteristics, survival analysis, in vitro and in vivo functional experiments, and the exploration of correlations between TMSB10 expression and immune cell infiltration. Our findings revealed a significant upregulation of TMSB10 expression in glioma tissues compared to normal brain tissues, with higher expression levels observed in tumors of advanced histological grades. Moreover, we observed positive correlations between TMSB10 expression and patient age, while no significant association with gender was detected. Additionally, TMSB10 exhibited marked elevation in gliomas with wild-type IDH and noncodeletion of 1p/19q. Survival analysis indicated that high TMSB10 expression was significantly associated with worse overall survival, disease-specific survival, and progression-free survival in glioma patients. Functionally, knockdown of TMSB10 in glioma cells resulted in reduced cellular growth rates and impaired tumor growth in xenograft models. Furthermore, our study revealed intriguing correlations between TMSB10 expression and immune cell infiltration within the tumor microenvironment. Specifically, TMSB10 showed negative associations with plasmacytoid dendritic cells (pDC) and γδ T cells (Tgd), while displaying positive correlations with neutrophils and macrophages. These findings collectively provide valuable insights into the oncogenic properties of TMSB10 in glioma, suggesting its potential as a therapeutic target and a biomarker for patient stratification.

Correlation between LSM1 Expression and Clinical Outcomes in Glioblastoma and Functional Mechanisms.

Background: Glioblastoma (GBM) is an aggressive form of brain tumor characterized by limited treatment options and a bleak prognosis. Although the role of Like-Sm 1 (LSM1), a component of the mRNA splicing machinery, has been studied in various cancers, its significance in GBM remains unclear. The purpose of this research was to investigate the expression of LSM1 and its role in driving GBM progression. Methods: We analyzed gene expression data obtained from TCGA and GTEx databases to compare the levels of LSM1 expression between GBM and normal brain tissues. To assess the impact of LSM1, we conducted experiments using U87 GBM cells, wherein we manipulated LSM1 expression through overexpression and knockdown techniques. These experiments allowed us to evaluate cellular behaviors such as proliferation and invasion. Additionally, we explored the correlation between LSM1 expression and immune cell infiltration in GBM. Results: Our analysis of TCGA and GTEx datasets revealed a significant upregulation of LSM1 expression in GBM compared to normal brain tissues. In our in vitro experiments using U87 cells, we observed that LSM1 overexpression promoted cell proliferation and invasion, while LSM1 knockdown exerted the opposite effects. Moreover, we discovered correlations between LSM1 expression and immune cell infiltration in GBM, specifically involving TFH cells, CD56bright cells, macrophages, and Th2 cells. Conclusions: The findings of this study demonstrate the upregulation of LSM1 in GBM and its contribution to tumor progression by enhancing cell proliferation, invasion, and influencing immune cell infiltration. Our research sheds light on the potential oncogenic role of LSM1 in GBM and suggests its viability as a therapeutic target for this aggressive brain tumor.

Molecular Signatures in Swine Innate and Adaptive Immune Responses to African Swine Fever Virus Antigens p30/p54/CD2v Expressed Using a Highly Efficient Semliki Forest Virus Replicon System.

African swine fever virus (ASFV) causes a devastating viral hemorrhagic disease in domestic pigs and Eurasian wild boars, posing a foremost threat to the swine industry and pig farming. The development of an effective vaccine is urgently needed, but has been hampered by the lack of an in-depth, mechanistic understanding of the host immune response to ASFV infection and the induction of protective immunity. In this study, we report that immunization of pigs with Semliki Forest Virus (SFV) replicon-based vaccine candidates expressing ASFV p30, p54, and CD2v, as well as their ubiquitin-fused derivatives, elicits T cell differentiation and expansion, promoting specific T cell and humoral immunity. Due to significant variations in the individual non-inbred pigs in response to the vaccination, a personalized analysis was conducted. Using integrated analysis of differentially expressed genes (DEGs), Venn, KEGG and WGCNA, Toll-like receptor, C-type lectin receptor, IL17 receptor, NOD-like receptor and nucleic acid sensor-mediated signaling pathways were demonstrated to be positively correlated to the antigen-stimulated antibody production and inversely correlated to the IFN-γ secreting cell counts in peripheral blood mononuclear cells (PBMCs). An up-regulation of CIQA, CIQB, CIQC, C4BPA, SOSC3, S100A8 and S100A9, and down-regulation of CTLA4, CXCL2, CXCL8, FOS, RGS1, EGR1 and SNAI1 are general in the innate immune response post-the second boost. This study reveals that pattern recognition receptors TLR4, DHX58/DDX58 and ZBP1, and chemokines CXCL2, CXCL8 and CXCL10 may play important roles in regulating this vaccination-stimulated adaptive immune response.

Construction and Transcriptomic Study of Chicken IFNAR1-Knockout Cell Line Reveals the Essential Roles of Cell Growth- and Apoptosis-Related Pathways in Duck Tembusu Virus Infection.

For industrial vaccine production, overwhelming the existing antiviral innate immune response dominated by type I interferons (IFN-I) in cells would be a key factor improving the effectiveness and production cost of vaccines. In this study, we report the construction of an IFN-I receptor 1 (IFNAR1)-knockout DF-1 cell line (KO-IFNAR1), which supports much more efficient replication of the duck Tembusu virus (DTMUV), Newcastle disease virus (NDV) and gammacoronavirus infectious bronchitis virus (IBV). Transcriptomic analysis of DTMUV-infected KO-IFNAR1 cells demonstrated that DTMUV mainly activated genes and signaling pathways related to cell growth and apoptosis. Among them, JUN, MYC and NFKBIA were significantly up-regulated. Furthermore, knockdown of zinc-fingered helicase 2 (HELZ2) and interferon-α-inducible protein 6 (IFI6), the two genes up-regulated in both wild type and KO-IFNAR1 cells, significantly increased the replication of DTMUV RNA. This study paves the way for further studying the mechanism underlying the DTMUV-mediated IFN-I-independent regulation of virus replication, and meanwhile provides a potential cell resource for efficient production of cell-based avian virus vaccines.

Establishment and Cross-Protection Efficacy of a Recombinant Avian Gammacoronavirus Infectious Bronchitis Virus Harboring a Chimeric S1 Subunit.

Infectious bronchitis virus (IBV) is a gammacoronavirus that causes a highly contagious disease in chickens and seriously endangers the poultry industry. A diversity of serotypes and genotypes of IBV have been identified worldwide, and the currently available vaccines do not cross-protect. In the present study, an efficient reverse genetics technology based on Beaudette-p65 has been used to construct a recombinant IBV, rIBV-Beaudette-KC(S1), by replacing the nucleotides 21,704-22,411 with the corresponding sequence from an isolate of QX-like genotype KC strain. Continuous passage of this recombinant virus in chicken embryos resulted in the accumulation of two point mutations (G21556C and C22077T) in the S1 region. Further studies showed that the T248S (G21556C) substitution may be essential for the adaptation of the recombinant virus to cell culture. Immunization of chicks with the recombinant IBV elicited strong antibody responses and showed high cross-protection against challenges with virulent M41 and a QX-like genotype IBV. This study reveals the potential of developing rIBV-Beau-KC(S1) as a cell-based vaccine with a broad protective immunity against two different genotypes of IBV.

Avian IRF1 and IRF7 Play Overlapping and Distinct Roles in Regulating IFN-Dependent and -Independent Antiviral Responses to Duck Tembusu Virus Infection.

Avian interferon regulatory factors 1 and 7 (IRF1 and IRF7) play important roles in the host's innate immunity against viral infection. Our previous study revealed that duck tembusu virus (DTMUV) infection of chicken fibroblasts (DF1) and duck embryo fibroblasts (DEFs) induced the expression of a variety of IFN-stimulated genes (ISGs), including VIPERIN, IFIT5, CMPK2, IRF1, and IRF7. IRF1 was further shown to play a significant role in regulating the up-expression of VIPERIN, IFIT5, and CMPK2 and inhibiting DTMUV replication. In this study, we confirm, through overexpression and knockout approaches, that both IRF1 and IRF7 inhibit DTMUV replication, mainly via regulation of type I IFN expression, as well as the induction of IRF1, VIPERIN, IFIT5, CMPK2, and MX1. In addition, IRF1 directly promoted the expression of VIPERIN and CMPK2 in an IFN-independent manner when IRF7 and type I IFN signaling were undermined. We also found that non-structural protein 2B (NS2B) of DTMUV was able to inhibit the induction of IFN-ß mRNA triggered by Newcastle disease virus (NDV) infection or poly(I:C) treatment, revealing a strategy employed by DTMUV to evade host's immunosurveillance. This study demonstrates that avian IRF7 and IRF1 play distinct roles in the regulation of type I IFN response during DTMUV infection.

Transcriptomic Analysis and Functional Characterization Reveal the Duck Interferon Regulatory Factor 1 as an Important Restriction Factor in the Replication of Tembusu Virus.

Duck Tembusu virus (DTMUV) infection has caused great economic losses to the poultry industry in China, since its first discovery in 2010. Understanding of host anti-DTMUV responses, especially the innate immunity against DTMUV infection, would be essential for the prevention and control of this viral disease. In this study, transcriptomic analysis of duck embryonic fibroblasts (DEFs) infected with DTMUV reveals that several innate immunity-related pathways, including Toll-like, NOD-like, and retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathways, are activated. Further verification by RT-qPCR confirmed that RIG-I, MAD5, TLR3, TLR7, IFN-α, IFN-ß, MX, PKR, MHCI, MHCII, IL-1ß, IL-6, (IFN-regulatory factor 1) IRF1, VIPERIN, IFIT5, and CMPK2 were up-regulated in cells infected with DTMUV. Through overexpression and knockdown/out of gene expression, we demonstrated that both VIPERIN and IRF1 played an important role in the regulation of DTMUV replication. Overexpression of either one significantly reduced viral replication as characterized by reduced viral RNA copy numbers and the envelope protein expression. Consistently, down-regulation of either one resulted in the enhanced replication of DTMUV in the knockdown/out cells. We further proved that IRF1 can up-regulate VIPERIN gene expression during DTMUV infection, through induction of type 1 IFNs as well as directly binding to and activation of the VIPERIN promoter. This study provides a genome-wide differential gene expression profile in cells infected with DTMUV and reveals an important function for IRF1 as well as several other interferon-stimulated genes in restricting DTMUV replication.

H7N9 Avian Influenza Virus Is Efficiently Transmissible and Induces an Antibody Response in Chickens.

H7N9 viruses pose a threat to human health and they are no less harmful to the poultry industry than the H5N1 avian influenza viruses. However, the pathogenesis, transmissibility, and the host immune response of the H7N9 virus in chickens and mice remain unclear. In this study, we found that H7N9 viruses replicated in multiple organs of the chicken and viral shedding persisted up to 30 days postinoculation (DPI). The viruses were efficiently transmitted between chickens through direct contact. Notably, chickens infected with H7N9 had high antibody levels throughout the entire observation period and their antibody response lasted for 30 DPI. The expression levels of the pattern-recognition receptors and pro-inflammatory cytokines were found to be significantly upregulated in the brain using quantitative real-time PCR. The expression of TLR3, TLR7, MDA5, Mx, IL-1ß, IL-6, IFN-α, and IFN-γ were also significantly different in the lungs of infected chickens. We found that the viruses isolated from these birds had low pathogenicity in mice, produced little weight loss and could only replicate in the lungs. Our findings suggested that the H7N9 viruses could replicate in chickens and mice and be efficiently transmitted between chickens, which presented a significant threat to human and poultry health.