Neutrophils are the most abundant leukocytes in peripheral blood and respond rapidly to danger, infiltrating tissues within minutes of infectious or sterile injury. Neutrophils were long thought of as simple killers, but now we recognise them as responsive cells able to adapt to inflammation and orchestrate subsequent events with some sophistication. Here, we discuss how these rapid responders release mediators which influence later adaptive T cell immunity through influences on DC priming and directly on the T cells themselves. We consider how the release of granule contents by neutrophils—through NETosis or degranulation—is one way in which the innate immune system directs the phenotype of the adaptive immune response.

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Orchestration of Adaptive T Cell Responses by Neutrophil Granule Contents

The inflammatory response to influenza A virus (H1N1): An experimental and mathematical study.

Exosomes are extracellular vesicles released by cells, both constitutively and after cell activation, and are present in different types of biological fluid. Exosomes are involved in the pathogenesis of diseases, such as cancer, neurodegenerative diseases, pregnancy disorders and cardiovascular diseases, and have emerged as potential non-invasive biomarkers for the detection, prognosis and therapeutics of a myriad of diseases. In this review, we describe recent advances related to the regulatory mechanisms of exosome biogenesis, release and molecular composition, as well as their role in health and disease, and their potential use as disease biomarkers and therapeutic targets. In addition, the advantages and disadvantages of their main isolation methods, characterization and cargo analysis, as well as the experimental methods used for exosome-mediated drug delivery, are discussed. Finally, we present potential perspectives for the use of exosomes in future clinical practice.

Exosomes: Potential Disease Biomarkers and New Therapeutic Targets.

The 2009 pandemic influenza A virus (IAV) H1N1 strain (H1N1pdm09) has widely spread and is circulating in humans and swine together with other human and avian IAVs. This fact raises the concern that reassortment between H1N1pdm09 and co-circulating viruses might lead to an increase of H1N1pdm09 pathogenicity in different susceptible host species. Herein, we explored the potential of different NS segments to enhance the replication dynamics, pathogenicity and host range of H1N1pdm09 strain A/Giessen/06/09 (Gi-wt). The NS segments were derived from (i) human H1N1- and H3N2 IAVs, (ii) highly pathogenic- (H5- or H7-subtypes) or (iii) low pathogenic avian influenza viruses (H7- or H9-subtypes). A significant increase of growth kinetics in A549 (human lung epithelia) and NPTr (porcine tracheal epithelia) cells was only noticed in vitro for the reassortant Gi-NS-PR8 carrying the NS segment of the 1918-descendent A/Puerto Rico/8/34 (PR8-wt, H1N1), whereas all other reassortants showed either reduced or comparable replication efficiencies. Analysis using ex vivo tracheal organ cultures of turkeys (TOC-Tu), a species susceptible to IAV H1N1 infection, demonstrated increased replication of Gi-NS-PR8 compared to Gi-wt. Also, Gi-NS-PR8 induced a markedly higher expression of immunoregulatory and pro-inflammatory cytokines, chemokines and interferon-stimulated genes in A549 cells, THP-1-derived macrophages (dHTP) and TOC-Tu. In vivo, Gi-NS-PR8 induced an earlier onset of mortality than Gi-wt in mice, whereas, six-week-old chickens were found to be resistant to both viruses. These data suggest that the specific characteristics of the PR8 NS segments can impact on replication, virus induced cellular immune responses and pathogenicity of the H1N1pdm09 in different avian and mammalian host species.

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NS Segment of a 1918 Influenza A Virus-Descendent Enhances Replication of H1N1pdm09 and Virus-Induced Cellular Immune Response in Mammalian and Avian Systems.

Lethal influenza A virus infection leads to acute lung injury and possibly lethal complications. There has been a continuous effort to identify the possible predictors of disease severity. Unlike earlier studies, where biomarkers were analyzed on certain time points or days after infection, in this study biomarkers were evaluated over the entire course of infection. Circulating proinflammatory cytokines and/or miRNAs that track with the onset and progression of lethal A/Puerto Rico/8/34 (PR8) influenza A virus infection and their response to oseltamivir treatment were investigated up to 10 days after infection. Changes in plasma cytokines (IL-1β, IL-10, IL-12p70, IL-6, KC, TNF-α, and IFN-γ) and several candidate miRNAs were profiled. Among the cytokines analyzed, IL-6 and KC/GRO cytokines appeared to correlate with peak viral titer. Over the selected 48 miRNAs profiled, certain miRNAs were up- or downregulated in a manner that was dependent on the oseltamivir treatment and disease severity. Our findings suggest that IL-6 and KC/GRO cytokines can be a potential disease severity biomarker and/or marker for the progression/remission of infection. Further studies to explore other cytokines, miRNAs, and lung injury proteins in serum with different subtypes of influenza A viruses with varying disease severity may provide new insight into other unique biomarkers.

/pdf/the-effect-of-oseltamivir-on-the-disease-progression-of-3m92cv55no.pdf

The Effect of Oseltamivir on the Disease Progression of Lethal Influenza A Virus Infection: Plasma Cytokine and miRNA Responses in a Mouse Model.

Well-characterized mice models will afford a cheaper, easy-handling opportunity for a more comprehensive understanding of 2009 influenza A (H1N1) virus’s pathogenesis potential. We aimed to provide a robust description of pulmonary immune responses in the mice infected by the virus. BALB/c mice were inoculated intranasally with A/Beijing/501/2009(H1N1) (BJ501) and A/PR/8/34(H1N1) (PR8) viruses and compared for survival rate, viral replication, and kinetics of pulmonary immune responses. BJ501 virus replicated less efficiently in the lungs than PR8, and both caused lethal illness in the mice. The transient increases of pulmonary TNF-α 2 days post infection for BJ501 and of INF-γ and IL-10 at 6 days post infection for PR8 were observed. IL-2+ and IL-4+ secreting cells showed significant increase 12 days post infection, while IFN-γ+, IgG+ and IgA+ secreting cells increased 6 days post infection. The different patterns of pulmonary immunological parameters between two viruses were at most seen in IL-6, IL-17 secretion and IgG1/IgG2a ratio. The BALB/c mouse is evaluated as a good pathogenic model for studying BJ501 2009 H1N1 virus. The work provided some basic and detailed data, which might be referred when further evaluating innate and adapted pulmonary immune responses and local viral load in mice.

/pdf/pulmonary-immune-responses-to-2009-pandemic-influenza-a-h1n1-32d93sdcy6.pdf

Pulmonary immune responses to 2009 pandemic influenza A (H1N1) virus in mice

Serum microRNAs (miRNAs) have been implicated as noninvasive biomarkers for lung cancer diagnosis. However, there are no sensitive and specific biomarkers for the detection of radiotherapy-related non-small cell lung cancer (NSCLC) metastasis. The present study aimed to investigate the role of three serum miRNAs, namely miRNA (miR)-130a, miR-25 and miR-191*, in diagnosing NSCLC, and their biological functions in radiation-mediated development of metastatic properties in A549 cells. To determine this, serum samples were collected from 84 patients with NSCLC and 42 age- and sex-matched healthy controls. Differential expression of serum miRNAs was analyzed by quantitative PCR. Significant associations between miRNA expression and overall survival of patients with NSCLC were identified using the Cox proportional regression model. A receiver operating characteristic curve was generated to evaluate diagnostic accuracy. The functions of miR-130a, miR-25 and miR-191* in lung cancer cells were studied by transfecting A549 cells with miRNA mimics and inhibitors. The results of the present study demonstrated that the expression levels of miR-130a, miR-25 and miR-191* in the serum of patients with NSCLC were increased compared with those in healthy controls, and these increases were associated with advanced age (≥60 years), radiotherapy, histological type (squamous carcinoma), low survival rate and low median survival time. Additionally, irradiation induced the upregulation of miR-130a, miR-25 and miR-191* expression in A549 cells in vitro and in a xenograft mouse model. Irradiation also promoted the invasiveness of A549 cells in vitro and metastasis in vivo. In conclusion, miR-130a, miR-25 and miR-191* may be potential biomarkers for the diagnosis of patients with NSCLC and may serve oncogenic roles in radiation-mediated metastasis of NSCLC.

/pdf/a-three-serum-mirna-panel-as-diagnostic-biomarkers-of-x7bat5i3g0.pdf

A three serum miRNA panel as diagnostic biomarkers of radiotherapy-related metastasis in non-small cell lung cancer.

Comparisons of the humoral and cellular immunity induced by live A16R attenuated spore and AVA-like anthrax vaccine in mice

Radiotherapy is a common strategy in treating lung cancer. Accumulating evidence suggested that radiotherapy has the potential to promote the metastasis and invasion of carcinoma cells. In this study, we aimed to testify the role of vascular endothelial growth factor (VEGF) and C-C chemokine receptor-7 (CCR-7) in the metastasis of human adenocarcinoma A549 cells in vivo and in vitro. Nude mice were injected with A549 cells irradiated by 0, 2 and 4 Gy X-rays, respectively. Quantitative detections of VEGF-A/C and CCR-7 mRNA from lung sample were performed by real-time RT-PCR. Small interfering RNA (siRNA) transfection technology was further used to testify the role of the genes in the metastasis of A549 cells. VEGF and CCR-7 mRNA could only be detected 10 weeks post injection in vivo when visible tumor foci scattered in lung. In addition, VEGF-A/C mRNA expressed significantly higher in mice injected with A549 cells irradiated by 2 and 4 X-rays than those with 0 Gy X-rays irradiation. On the other hand, A549 cells with or without X-rays irradiation transfected with VEGF siRAN and CCR-7 siRNA showed a dramatic decrease of invasiveness compared to normal A549 cells with or without irradiation. The migration indexes were −0.7, −0.48, −0.34 and −0.32 for A549 cells with CCR-7 siRNA, VEGF siRNA, X-rays combined CCR-7 siRNA and X-rays combined VEGF-siRNA respectively. These results demonstrated that X-rays could promote the metastasis of A549 cells, and VEGF-A/C and CCR-7 mRNA were closely related to the metastasis of A549 cells in vivo and in vitro.

Role of VEGF-A/C and CCR-7 in the enhanced metastasis of A549 cells induced by 2 and 4 Gy X-rays in vitro and in vivo

Inadequate potassium (K) availability is a common abiotic stress that limits the growth and quality of fruit trees. Few studies have investigated the physiological and molecular responses of grapes at different potassium levels. In this study, an integrated approach was developed for grapevines grown at four different potassium fertilization levels [0 (K0-CK), 150 (K150), 300 (K300), and 450 (K450) g/plant] in combination with metabolite measurements and transcript analysis. The results showed that different K levels affected the accumulation of sugars and anthocyanins in the fruit. At 78 days after bloom (DAB), the K150, K300, and K450 treatments increased soluble sugar content by 37.39%, 31.10% and 32.59%, respectively, and anthocyanin content by 49.78%, 24.10%, and 13.06%, respectively, compared to K0. Weighted gene co-expression network analysis (WGCNA) of DEGs identified a network of 11 grapevines involved. During fruit development, potassium application promoted the accumulation of anthocyanins and sugars in fruit by regulating the up-regulation of GST, AT, UFGT and SPS, HT, PK gene expressions. These results suggest that potassium deficiency inhibits anthocyanin and sugar metabolism. In addition, it promotes the up-regulation of KUP expression, which is the main cause of K accumulation in fruits. Together, our data revealed the molecular mechanism in response to different K levels during fruit quality formation and provides the scientific foundation for the improvement of fruit quality by adding K fertilizer.

https://www.mdpi.com/1422-0067/24/2/1218/pdf?version=1674009740

Wen-Wei Hu

Papers

Pulmonary immune responses to 2009 pandemic influenza A (H1N1) virus in mice

A three serum miRNA panel as diagnostic biomarkers of radiotherapy-related metastasis in non-small cell lung cancer.

Comparisons of the humoral and cellular immunity induced by live A16R attenuated spore and AVA-like anthrax vaccine in mice

Role of VEGF-A/C and CCR-7 in the enhanced metastasis of A549 cells induced by 2 and 4 Gy X-rays in vitro and in vivo

Identification of Key Genes Induced by Different Potassium Levels Provides Insight into the Formation of Fruit Quality in Grapes