Rheumatoid arthritis (RA) is widespread globally, with the emergence of metabolites derived from both the host and microbes playing a pivotal role in its pathogenesis. This study aims to elucidate the relationships between serum metabolites and the immunological and clinical features of RA. Serum samples were collected from 35 RA patients and 37 healthy controls (HC). Metabolite profiling was performed using gas chromatography-mass spectrometry (GC/MS). Principal component analysis revealed a significant distinction between the RA and HC cohorts. Employing univariate statistical analysis, we identified 36 differential metabolites. Among these, 9 metabolites, including galactose and glucose, were found to be enriched, while the remaining metabolites, such as citric acid, fumaric acid, and inosine, were depleted in RA. These diverse metabolites encompassed various metabolic processes, including the biosynthesis of fatty acids, amino acids, and glucose. The enrichment of glucose and galactose in RA exhibited a substantial correlation with elevated IgG levels, as determined through correlation analysis. Conversely, the depletion of citric acid was correlated with elevated levels of C3 and CRP. Methionine, which also declined in RA patients, displayed a negative correlation with ESR. Furthermore, galactose and glucose exhibited significant positive correlations with naïve B cells, while the decreased eicosanoic acid level in RA was significantly associated with an increase in natural killer cells. Our findings suggest that the altered serum metabolite profile in RA is closely linked to disease severity and the dysregulated immune responses observed in RA patients. Key Points • Identified nine metabolites with upregulated expression and twenty-seven metabolites with downregulated expression.• Established a correlation between alterations in serum metabolite levels and inflammatory markers in RA patients.• Discovered a significant association between changes in serum metabolites and immune cell profiles in RA patients.

Currently, the coronavirus disease 2019 (COVID-19) is becoming a serious threat to human health worldwide. Therefore, there is a great need to develop effective drugs against viral pneumonia. Diammonium glycyrrhizinate (DG), derived from Glycyrrhiza glabra L., has been demonstrated with significant anti-inflammatory properties. However, the therapeutic effects and mechanisms of DG on pneumonia require further clarification. In this study, mice received intratracheal injection of polyinosinic–polycytidylic acid (poly(I:C)) to induce pneumonia and were treated with DG. First, we evaluated the therapeutic potential of DG on poly(I:C)-induced pneumonia. Second, the anti-inflammatory and antioxidative activities and the impact of DG on the toll-like receptor 3 (TLR3) pathway were investigated. Third, the mechanism of DG was analyzed through untargeted metabolomics techniques. Our results revealed that DG intervention decreased permeability and reduced abnormal lung alterations in poly(I:C)-induced pneumonia model mice. DG intervention also downregulated cytokine levels in bronchoalveolar lavage fluid. Moreover, DG treatment inhibited the activation of TLR3 pathway. Furthermore, untargeted metabolomics analysis revealed that DG intervention could modulate serum metabolites involved in amino and nucleotide sugar metabolism, fructose and mannose metabolism, tyrosine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis pathways. In conclusion, our study showed that DG could ameliorate poly(I:C)-induced pneumonia by inactivating the TLR3 pathway and affecting amino and nucleotide sugar, fructose and mannose metabolism, as well as tryptophan, phenylalanine, and tyrosine biosynthesis.

Apolipoprotein E (ApoE) participates in lipoprotein metabolism and immune regulation. This study assessed association between ApoE polymorphisms with hyperuricemia and uric acid metabolism in Uygur men, Xinjiang, China. A total of 474 hyperuricemia patients and 518 healthy male controls were recruited from the Health Screening Center, Uygur region of Xinjiang, China and subjected to ApoE genotyping using a multiplex amplification refractory mutation system PCR. Apolipoprotein E3/3 genotype was the predominant type with a frequency of 67.7%, while E2/2 was lower than E4/4 in Uygur males. The frequencies of ApoE2, E3, and E4 alleles were 8.5%, 80.1% and 11.4%, respectively. Distribution of ApoE genotypes was significantly different in hyperuricemia patients from the healthy controls (p < 0.001). Particularly, the frequency of ApoE E3/3 was 71.7%, E2/3 9.3%, E3/4 9.3%, E4/4 3.2%, E2/4 2.3%, and E2/2 0.2% in patients vs. 68.1%, 4.6%, 2.9%, 12%, 0.6%, and 4.6% in controls, respectively. Moreover, frequency of ApoE E2 allele was greater in the healthy controls than in patients (p < 0.001) and the highest level of uric acid occurred in those with ApoE2/4 and E3/4 genotypes, whereas the lowest uric acid level occurred in those with ApoE E2/2 genotype. In addition, the subjects with the ApoE2 allele had a lower uric acid and LDL-C level than those with the ApoE3 allele and ApoE4 allele (p < 0.05). The risk of developing hyperuricemia in subjects without the ApoE2 allele was 1.7 fold higher than those subjects with the ApoE2 allele. This study revealed frequencies and distributions of ApoE alleles and genotypes in Uygur males, which are different from Han Chinese. ApoE E4 was associated with a slightly higher risk of primary hyperuricemia, whereas ApoE E2 was associated with reduced risk of primary hyperuricemia and LDL-C level.

Background: Identification of combined T-cell and B-cell reactive Eg95 antigens for the potential development of a multi-epitope vaccine against Echinococcus granulosus (EG), the causative agent of cystic echinococcosis (CE). Methods: This study involved the recombinant expression of Eg95 along with associated immune rabbit antiserum preparation. Bioinformatics technology was used to facilitate the analysis of Eg95 molecules. PCR was subsequently used to amplify genetic sequences of the epitopes encoding the T-cell and B-cell reactive peptide fragments. SDS-PAGE was used to assess the expression levels of three proteins. Eg95 serum and patient antiserum, which were assessed using Western blot in order to identify suitable antigenic epitope peptides. ELISA detection assay facilitated comparison of the immune reactivity of the short peptide epitopes. The assay results could be used to determine an EG epitope-based vaccine candidate list from suitably reactive Eg95 epitopes. Results: Eg95 molecules have 3 T-B table. The phage display systems were successfully built using the M13KE carrier. Expression of the three fusion protein peptides were detected. Western blot showed Eg95 antiserum against EG facilitated identification of the three T-cell and B-cell reactive epitopes. After the reaction intensities analyzed by the ELISA, both of the short peptide epitopes Eg95-2 and Eg95-3 showed strong signal strength and associated antigenicity when combined with patient serum and rabbit anti-rEg95 serum. Conclusions: This study used bioinformatics methods to construct successfully a T-cell and B-cell epitope phage display system for the Eg95 antigen from EG. The two epitopes of Eg95-2 and Eg95-3 demonstrated strong antigenicity with potential applications for peptide vaccine development.

Full Papers; Authors: S. Cao, X. Liu, Y. Li, Y. Yang, X. Cai, S. Cong, Z. Li, Y. Li, Y. Hong, Y. Su, Z. Li, L. Luo, X. Sun