The mRNA Vaccine Expressing Single and Fused Structural Proteins of Porcine Reproductive and Respiratory Syndrome Induces Strong Cellular and Humoral Immune Responses in BalB/C Mice.

PRRS is a viral disease that profoundly impacts the global swine industry, causing significant economic losses. The development of a novel and effective vaccine is crucial to halt the rapid transmission of this virus. There have been several vaccination attempts against PRRSV using both traditional and alternative vaccine design development approaches. Unfortunately, there is no currently available vaccine that can completely control this disease. Thus, our study aimed to develop an mRNA vaccine using the antigens expressed by single or fused PRRSV structural proteins. In this study, the nucleotide sequence of the immunogenic mRNA was determined by considering the antigenicity of structural proteins and the stability of spatial structure. Purified GP5 protein served as the detection antigen in the immunological evaluation. Furthermore, cellular mRNA expression was detected by immunofluorescence and western blotting. In a mice experiment, the Ab titer in serum and the activation of spleen lymphocytes triggered by the antigen were detected by ELISA and ICS, respectively. Our findings demonstrated that both mRNA vaccines can significantly stimulate cellular and humoral immune responses. More specifically, the GP5-mRNA exhibited an immunological response that was similar to that of the commercially available vaccine when administered in high doses. To conclude, our vaccine may show promising results against the wild-type virus in a natural host.

Changes in serum tumor markers in type 2 diabetes mellitus with microalbuminuria.

Objectives: The objective of this study was to investigate changes in serum tumor markers in type 2 diabetes mellitus (T2DM) with microalbuminuria and analyze the relationship between tumor markers and microalbuminuria. Methods: A total of 956 T2DM patients aged 40-70 years hospitalized in the Department of Endocrinology, Xinhua Hospital, China, affiliated with Shanghai Jiaotong University School of Medicine, were enrolled from January 2018 to December 2020. The sample comprised 313 T2DM patients with microalbuminuria and 643 T2DM patients with normal urinary microalbumin levels. After assessing the changes in serum tumor markers in T2DM with microalbuminuria, we analyzed the risk of microalbuminuria by the serum tumor marker category using multiple logistic regression analysis. Results: Serum CEA, CA199, CA125, CA153, CA211, SCC, CA242, and CA50 levels were significantly higher in T2DM patients with microalbuminuria than in those without microalbuminuria, while serum AFP levels were lower in the microalbuminuria group (P < 0.05). Following adjustment of confounders, serum CEA, CA211, and SCC were independently associated with microalbuminuria in T2DM. An ROC curve was used to estimate the cutoff point of tumor markers for microalbuminuria. Taking the values under the cutoff points as a reference, values for CEA, CA211, and SCC above the cutoff points indicated a significantly high risk of microalbuminuria. The OR of increased CEA for microalbuminuria was 2.006 (95%CI 1.456-2.765), the OR of increased CA211 for microalbuminuria was 1.505 (95%CI 1.092-2.074), and the OR of increased SCC for microalbuminuria was 1.958 (95%CI 1.407-2.724). Conclusion: Several serum tumor markers were related to microalbuminuria in T2DM. Serum tumor markers such as CEA, SCC, and CA211 may indicate early diabetic nephropathy, particularly when elevated in combination.

Suppression of Alzheimer's disease-related phenotypes by the heat shock protein 70 inducer, geranylgeranylacetone, in APP/PS1 transgenic mice via the ERK/p38 MAPK signaling pathway.

HSP70 overexpression has a remedying effect in neurodegenerative diseases. In Alzheimer's disease (AD), the suppressive effects of HSP70 overexpression on AD-related phenotypes and the underlying mechanisms are unknown. In the current study, the effect of geranylgeranylacetone (GGA), a non-toxic inducer of heat shock protein (HSP)-70 expression, on cognitive function and other pathological phenotypes were evaluated in APP/PS1 mice. It was observed that all doses of orally administered GGA (200, 400, and 800 mg/kg/day) improved cognitive deficit (P<0.05) and lowered the levels of amyloid-ß (Aß) peptide (P<0.05) in APP/PS1 mice. GGA treatment also increased the levels of low density lipoprotein receptor-related protein 1 (LRP-1) (P<0.05), while the levels of p-glycoprotein and receptor for advanced glycation end products were unaltered. Significant decreases in the levels of inflammatory cytokines, namely tumor necrosis factor-α, interleukin-1ß and cyclooxygenase-2, were also observed in the GGA-treated mice (P<0.05). Subsequent treatment with the HSP70 inhibitor quercetin caused significant decreases in the levels of phosphorylated (p)-p38 mitogen-activated protein kinase (p38 MAPK) and p-extracellular signal-regulated protein kinases (ERK; P<0.05), indicating that ERK/p38 MAPK signaling in AD-related phenotypes may be suppressed by oral administration of GGA. Finally, in APP/PS1 mice treated with GGA+SB-203580 (p38 inhibitor) and GGA+PD98059 (ERK inhibitor), it was observed that orally administered GGA led to the activation of ERK/p38 MAPK signaling (P<0.05) and increased LRP-1 expression (P<0.05), which subsequently aided the clearance of Aß40 and Aß42 (P<0.05) and alleviated AD-related phenotypes. These results indicate that oral administration of GGA in APP/PS1 mice alleviates AD-related phenotypes by regulation of the ERK/p38 MAPK signaling pathway. Thus, GGA may be a potential therapeutic for the treatment of AD.