red-blood-cell-distribution-width-to-albumin-ratio-migraine

Red Blood Cell Distribution Width-to-Albumin Ratio and Migraine: Associations with Prevalence and All-Cause Mortality in a Population-Based Study

Migraine is a common primary neurovascular disorder&#160;associated with substantial morbidity and systemic inflammatory alterations. The red blood cell ...

Nanjing University

The human diploid cell line Medical Research Council -5 (MRC-5) is commonly utilized for vaccine development. Although a rabies vaccine developed in cultured MRC-5 cells exists, the poor susceptibility of MRC-5 cells to the rabies virus (RABV) infection limits the potential yield of this vaccine. The underlying mechanism of MRC-5 cell resistance to RABV infection remains unknown. In this study, we demonstrate that viral infection increased exosomal release from MRC-5 cells; conversely, blocking exosome release promoted RABV infection in MRC-5 cells. Additionally, RABV infection up-regulated microRNA (miR)-423-5p expression in exosomes, resulting in feedback inhibition of RABV replication by abrogating the inhibitory effect of suppressor of cytokine signaling 3 (SOCS3) on type I interferon (IFN) signaling. Furthermore, intercellular delivery of miR-423-5p by exosomes inhibited RABV replication in MRC-5 cells. We also show that RABV infection increased IFN-β production in MRC-5 cells and that blocking the type I IFN receptor promoted RABV infection. In conclusion, MRC-5 cells were protected from RABV infection by the intercellular delivery of exosomal miR-423-5p and the up-regulation of IFN-β. These findings reveal novel antiviral mechanisms in MRC-5 cells against RABV infection. miR-423-5p, exosomes, and IFN signaling pathways may therefore be potential targets for improving MRC-5 cell-based rabies vaccine production.

Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection.

The Enterovirus 71 (EV71) VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue. However, the role of this myristoylation in the EV71 life cycle remains largely unknown. To investigate this issue, we developed a myristoylation-deficient virus and reporter (luciferase) pseudovirus with a Gly-to-Ala mutation (G2A) on EV71 VP4. When transfecting the EV71-G2A genome encoding plasmid in cells, the loss of myristoylation on VP4 did not affect the expression of viral proteins and the virus morphology, however, it did significantly influence viral infectivity. Further, in myristoylation-deficient reporter pseudovirus-infected cells, the luciferase activity and viral genome RNA decreased significantly as compared to that of wild type virus; however, cytopathic effect and viral capsid proteins were not detected in myristoylation-deficient virus-infected cells. Also, although myristoylation-deficient viral RNA and proteins were detected in the second blind passage of infection, they were much fewer in number compared to that of the wild type virus. The replication of genomic RNA and negative-strand viral RNA were both blocked in myristoylation-deficient viruses, suggesting that myristoylation affects viral genome RNA release from capsid to cytoplasm. Besides, loss of myristoylation on VP4 altered the distribution of VP4-green fluorescent protein protein, which disappeared from the membrane structure fraction. Finally, a liposome leakage assay showed that EV71 myristoylation mediates the permeability of the model membrane. Hence, the amino-terminal myristoylation of VP4 is pivotal to EV71 infection and capsid-membrane structure interaction. This study provides novel molecular mechanisms regarding EV71 infection and potential molecular targets for antiviral drug design.

Myristoylation of EV71 VP4 is Essential for Infectivity and Interaction with Membrane Structure.

T cell-engaging therapies involving bispecific T cell engager (BiTE) and chimeric antigen receptor T (CAR-T) cells have achieved great success in the treatment of hematological tumors. However, the paucity of ideal cell surface molecules that can be targeted on glioblastoma (GBM) partially reduces the immunotherapeutic efficacy. Recently, high expression of Fn14 has been reported in several solid tumors, so the strategy of exploiting this specific antigen for GBM immunotherapy is worth studying. Consequently, we constructed Fn14× CD3 BiTE and Fn14-specific CAR-T cells and investigated their cytotoxic activity against GBM in vitro and in vivo. First, expression of Fn14 was confirmed in glioma tissues and GBM cells. Then, we designed Fn14-specific BiTE and CAR-T cells and tested their cytotoxicity in GBM cell cultures and mouse models of GBM. Fn14 was highly expressed in GBM tissues and cell lines, while it was undetectable in normal brain samples. Fn14× CD3 BiTE, Fn14 CAR-T cells and Fn14 CAR-T/IL-15 cells were antigen-specific and highly cytotoxic, showing good antitumor activity in vitro and causing significant regression of established solid tumors in xenograft models. However, the xenografts treated with Fn14 CAR-T cells regrew, whereas xenografts treated with Fn14 CAR-T/IL-15 cells did not. IL-15 engineering augmented the antitumor activity of Fn14 CAR-T cells and resulted in significant antitumor effects similar to those of Fn14× CD3 BiTE. Our results suggest that Fn14 is an appropriate target for GBM. Anti-Fn14 BiTE and Fn14-specific CAR-T/IL-15 cells may be exciting immunotherapeutic options for malignant brain cancer.

Fn14-targeted BiTE and CAR-T cells demonstrate potent preclinical activity against glioblastoma.

In the absence of pathogen attack, lesion mimic mutants (LMMs) in plants undergo spontaneous cell death and develop necrosis or apoptosis-like lesions on the leaves or sheath, resembling symptoms of hypersensitive response. In-depth research has been conducted on LMMs, especially regarding the molecular mechanisms underlying programmed cell death and disease resistance. In this study, the  () mutant was identified as a typical LMM, showing lesions on both the leaf blade and leaf sheath. The formation of lesions was found to be caused by cell death accompanied by accumulation of hydrogen peroxide and degradation of chloroplasts. Compared with wild-type, the main agronomic traits such as plant height, effective panicle number, panicle length, grain per panicle, seed setting rate, and 1000-grain weight of  were significantly reduced. The defence and pathogenesis-related genes , , , and , were transcriptionally activated in mutant  without pathogen attack. Genetic analysis showed that the mutant phenotype was controlled by the gene , which was mapped to an interval of 260 kb at the end of the long arm on chromosome 11. Pathogen inoculation analysis showed that  has enhanced resistance to sheath blight, rice blast, and bacterial blight.

Identification and fine mapping of lesion mimic mutant  in rice ( L.).

Objective: T lymphocytes, complement, and immunoglobulin play an important role in neuromyelitis optica spectrum disorders (NMOSD). As common clinical examination indicators, they have been used as routine indicators in many hospitals, which is convenient for being carried out in clinical work, but there are few articles of guiding significance for clinical practice. The purpose of this study was to study the relationship between commonly used immune indicators and clinical characteristics in patients with NMOSD. Methods: We compared clinical characteristics and clinical immune indicators in 258 patients with NMOSD and 200 healthy controls (HCs). We used multiple linear regression to study the relationship between immunotherapy, disease phase, sex, age, AQP4-IgG, and immune indicators. In addition, lymphocyte subsets were compared before and after immunotherapy in 24 of the 258 patients. We explored the influencing factors and predictors of severe motor disability. Results: The percentages of CD3 ratio (71.4% vs. 73.8%, p = 0.013), CD4 ratio (38.8% vs. 42.2%, p < 0.001), and CD4/CD8 ratio (1.43 vs. 1.66, p < 0.001) in NMOSD patients were significantly lower than those in the HC group. In addition, complement C4 (0.177 g/L vs. 0.221 g/L, p < 0.001) and peripheral blood IgG (10.95 g/L vs. 11.80 g/L, p = 0.026) in NMOSD patients were significantly lower than those in the HC group. CD3 percentage was correlated with blood collection age and disease stage; CD8 percentage was correlated with blood collection age, disease stage, and treatment; CD4/CD8 percentage was correlated with blood collection age and treatment; complement C4 was correlated with blood collection age and sex; and IgG was correlated with disease stage and treatment. Twenty-four patients before and after treatment showed that the percentages of CD3 ratio (74.8% vs. 66.7%, p = 0.001) and CD8 ratio (32.4% vs. 26.2%, p < 0.001) after treatment in NMOSD patients were significantly increased, and the percentage of CD3 before treatment was moderately negatively correlated with ARR (r = −0.507, p = 0.011). Binary logistic regression analysis showed that peripheral blood complement C3 is a serious influencing factor for severe motor disability (EDSS score ≥ 6 points). Peripheral blood complement C3 and C4 are predictors of severe motor disability (p < 0.05). Conclusion: Our results suggest that peripheral blood T lymphocytes, C3, C4 and immunoglobulin are convenient and routine clinical indicators that are convenient for implementation in clinical work. They have certain reference values for disease staging, recurrence, drug efficacy, and motor disability. They have improved our understanding of clinical immune indicators for NMOSD patients, but whether they can be used as biomarkers for clinical prognosis remains to be further studied.

Relationship between the Clinical Characteristics in Patients with Neuromyelitis Optica Spectrum Disorders and Clinical Immune Indicators: A Retrospective Study.

Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia due to aging or immunosuppression. Glycoprotein E (gE) is a widely used vaccine antigen for specific humoral and cellular immune responses. Immediate early protein 63 (IE63) is expressed during latency, suggesting that it is a potential antigen against HZ reactivation. In this study, HZ DNA vaccines encoding gE, IE63, IE63-2A-gE (where 2A is a self-cleaving sequence), or IE63-linker-gE were developed and investigated for immunogenicity in mice. The results showed that each HZ DNA vaccine induced VZV-specific antibody production. The neutralizing antibody titer elicited by IE63-2A-gE was comparable to that elicited by gE or live attenuated HZ vaccine (LAV). IE63-2A-gE-induced gE or IE63-specific INF-γ T cell frequencies in splenocytes were comparable to those of LAV. Furthermore, IE63-2A-gE, gE, or IE63 led to a significant increase in IFN-γ (IE63 stimulation) and IL-2 (gE stimulation) secretion compared to LAV, showing a Th1-biased immune response. Moreover, IE63-2A-gE and gE induced cytotoxic activity of CD8 T cells compared to that of LAV. This study elucidates that the IE63-2A-gE DNA vaccine can induce both humoral and cell-mediated immune responses, which provides a candidate for the development of an HZ vaccine.

Article	Year
Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection. International journal of molecular sciences\| PubMed ID: 30934732	2019
Myristoylation of EV71 VP4 is Essential for Infectivity and Interaction with Membrane Structure. Virologica Sinica\| PubMed ID: 32399947	2020
Fn14-targeted BiTE and CAR-T cells demonstrate potent preclinical activity against glioblastoma. Oncoimmunology\| PubMed ID: 34595061	2021
Identification and fine mapping of lesion mimic mutant in rice ( L.). Breeding science\| PubMed ID: 35087315	2021
Relationship between the Clinical Characteristics in Patients with Neuromyelitis Optica Spectrum Disorders and Clinical Immune Indicators: A Retrospective Study. Brain sciences\| PubMed ID: 35326328	2022
Immunogenicity of Varicella Zoster Virus DNA Vaccines Encoding Glycoprotein E and Immediate Early Protein 63 in Mice. Viruses\| PubMed ID: 35746685	2022

Linjun Cai

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