The major immediate early (MIE) gene of cytomegalovirus plays a key role in determining the activation and replication of cytomegalovirus, which represents the most important event signaling the onset of virus-induced disease relapse. The viral-encoded chemokine receptor homolog US28 can constitutively activate many cellular transcription factors, which can bind to the promoter/enhancer of the MIE gene and activate its transcription. Using reporter gene assays in HEK293 cells, we found that US28 enhanced the transcription efficiency of MIE and other genes via cAMP response element-binding protein (CREB). Inhibition of CREB partially blocked the effect of US28, whereas forskolin enhanced this effect. There was a direct correlation between CREB and transcription of MIE gene. These data, together with the broad-spectrum effect of cellular transcription factors, suggest that US28 may be involved in the very early transcription of the host cell during virus activation.
IntroductionHeat-related illnesses can lead to morbidity, which are anticipated to increase frequency with predictions of increased global surface temperatures and extreme weather events. Although heat acclimation training (HAT) could prevent heat-related diseases, the mechanisms underlying HAT-promoting beneficial changes in organ function, immunity, and gut microbes remain unclear.MethodsIn the current study, we recruited 32 healthy young soldiers and randomly divided them into 4 teams to conduct HATs for 10 days: the equipment-assisted training team at high temperature (HE); the equipment-assisted training team under normal hot weather (NE); the high-intensity interval training team at high temperature (HIIT), and the control team without training. A standard heat tolerance test (HTT) was conducted before (HTT-1st) and after (HTT-2nd) the training to judge whether the participants met the heat acclimation (HA) criteria.ResultsWe found that the participants in both HE and NE teams had significantly higher acclimation rates (HA/total population) than whom in the HIIT team. The effects of HAT on the participants of the HE team outperformed that of the NE team. In the HA group, the differences of physiological indicators and plasma organ damage biomarkers (ALT, ALP, creatinine, LDH, α-HBDH and cholinesterase) before and after HTT-2nd were significantly reduced to those during HTT-1st, but the differences of immune factors (IL-10, IL-6, CXCL2, CCL4, CCL5, and CCL11) elevated. The composition, metabolism, and pathogenicity of gut microbes changed significantly, with a decreased proportion of potentially pathogenic bacteria (Escherichia-Shigella and Lactococcus) and increased probiotics (Dorea, Blautia, and Lactobacillus) in the HA group. Training for a longer time in a high temperature and humidity showed beneficial effects for intestinal probiotics.ConclusionThese findings revealed that pathogenic gut bacteria decrease while probiotics increase following HA, with elevated immune factors and reduced organ damage during heat stress, thereby improving the body’s heat adaption.
Protein microarray has progressed rapidly in the past few years, but it is still hard to popularize it in many developing countries or small hospitals owing to the technical expertise required in practice. We developed a cheap and easy-to-use protein microarray based on dot immunogold filtration assay for parallel analysis of ToRCH-related antibodies including Toxoplasma gondii, rubella virus, cytomegalovirus and herpes simplex virus type 1 and 2 in sera of pregnant women. It does not require any expensive instruments and the assay results can be clearly recognized by the naked eye. We analyzed 186 random sera of outpatients at the gynecological department with our microarray and commercial ELISA kit, and the results showed there was no significant difference between the two detection methods. Validated by clinical application, the microarray is easy to use and has a unique advantage in cost and time. It is more suitable for mass prenatal screening or epidemiological screening than the ELISA format.
RATIONALE: Previously we have shown increased A Proliferation-Inducing Ligand (APRIL) and B-cell Activation Factor (BAFF) concentrations in colostrum are associated with protection against allergic disease. APRIL and BAFF, together with IL-10 and TGFb, are known to induce T-cell independent (TI) IgA class switch recombination (CSR) in Bcells. Our goal was to assess whether human milk containing these cytokines, would induce CSR in cord blood B-cells. METHODS: B-cells were isolated from cord blood mononuclear cells (CBMCs) by IgD selection and were then cultured for 3-7 days with treatments: culture medium containing human milk or combination of APRIL and TGFb1. Cells were then analyzed by flow cytometry for detection of IgA1 and IgA2 positive B-cells. RESULTS: B-cell CSR assay protocols were established. IgA B-cells were readily detectable following the assay protocol, using APRIL and TGFb1 stimulation as positive controls. Using the protocol we noted a robust IgA class switching following stimulation using sterile filtered human milk. CONCLUSIONS: We have established a protocol that will allow more detailed assessment of several cytokines in human milk class switch recombination. Future experiments will characterize in detail which cytokines affect CSR and IgA production to elicit the role of human milk in protection against onset of allergic disease.
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