The decreased of peripheral blood natural killer cell is associated with serum IL-2 level in the renal tubular acidosis in patients with primary sjogren's syndrome.

BACKGROUND: Primary Sjogren's Syndrome (pSS) is a lymphoproliferative disease with autoimmune characteristics, which is characterized by lymphocyte infiltration of exocrine glands and involvement and dysfunction of extraglandular organs. Renal tubular acidosis (RTA) is a common renal involvement in pSS. This study investigated the phenotypic characteristics of peripheral blood lymphocyte subsets and cytokines in pSS patients complicated with RTA (pSS-RTA). METHOD: This retrospective study included 25 pSS patients complicated with RTA and 54 pSS patients without RTA (pSS-no-RTA). To examine the level of peripheral lymphocytes subsets, flow cytometry analysis was used. The level of serum cytokines were detected by flow cytometry bead array(CBA). The influencing factors related to the occurrence of pSS-RTA were identified through logistic regression analyze. RESULTS: The absolute number of CD4 + T cells and Th2 cells in peripheral blood were decreased in pSS-RTA patients than pSS-no-RTA patients. Moreover, the absolute number of NK cells and Treg cells were also decreased in pSS-RTA patients than pSS-no-RTA. The level of serum IL-2 was higher in pSS-RTA patients than pSS-no-RTA patients, and is negatively correlated with the number of NK cells, the number and percentage of Th17 cells, and Th17/Treg. Serum IL-2 level is also correlated with various cytokines. Multivariate logistic analysis proved that elevated ESR and ALP were risk factors for pSS complicated with RTA, while Treg was a protective factor. CONCLUSION: The increase of serum IL-2 level and the decrease of peripheral blood NK cells and Treg cells may be the immune mechanism of the development of pSS-RTA disease.

Impaired immune tolerance mediated by reduced Tfr cells in rheumatoid arthritis linked to gut microbiota dysbiosis and altered metabolites.

BACKGROUND: Patients with rheumatoid arthritis (RA) showed impaired immune tolerance characterized by reduced follicular regulatory T (Tfr) cells, and they also exhibited altered gut microbiotas and their metabolites in RA. However, the association of gut microbiotas and their metabolites with the immune tolerance mediated by Tfr cells in RA remains unclear. METHODS: Peripheral blood and stool samples were collected from 32 new-onset RA patients and 17 healthy controls (HCs) in the Second Hospital of Shanxi Medical University between January 2022 and June 2022. The peripheral blood was used to detect the circulating regulatory T (Treg), helper T(Th)17, Tfr, and follicular helper T (Tfh) cells by modified flow cytometry. The stool samples were used to analyze the gut microbiotas and their metabolites via 16S rDNA sequencing and metabolomic profiling. We aimed to characterize the gut microbiotas and their metabolites in RA and identified their association with Tfr cell-mediated immune tolerance. RESULTS: The new-onset RA demonstrated reduced Treg and Tfr cells, associated with the disease activity and autoantibodies. There were significant differences in gut microbiotas between the two groups as the results of ß diversity analysis (P = 0.039) including 21 differential gut microbiotas from the phylum to genus levels. In which, Ruminococcus 2 was associated with the disease activity and autoantibodies of RA, and it was identified as the potential biomarker of RA [area under curve (AUC) = 0.782, 95% confidence interval (CI) = 0.636-0.929, P = 0.001]. Eleven differential metabolites were identified and participated in four main pathways related to RA. Arachidonic acid might be the potential biomarker of RA (AUC = 0.724, 95% CI = 0.595-0.909, P = 0.038), and it was the core metabolite as the positive association with six gut microbiotas enriched in RA. The reduced Tfr cells were associated with the altered gut microbiotas and their metabolites including the Ruminococcus 2, the arachidonic acid involved in the biosynthesis of unsaturated fatty acid pathway and the 3-methyldioxyindole involved in the tryptophan metabolism pathway. CONCLUSION: The breakdown of immune tolerance mediated by reduced Tfr cells was associated with the altered gut microbiotas and their metabolites implying the possible mechanism of RA pathogenesis from the perspective of microecology-metabolism-immune.

The Level of Histone Deacetylase 4 is Associated with Aging Cartilage Degeneration and Chondrocyte Hypertrophy.

Purpose: To determine the role of histone deacetylase 4 (HDAC4)-controlled chondrocyte hypertrophy in the onset and development of age-related osteoarthritis (OA). Methods: Morphological analysis of human knee cartilages was performed to observe structural changes during cartilage degeneration. HDAC4 expression was deleted in adult aggrecan (Acan)-CreERT2; HDAC4fl/fl transgenic mice. The onset and development of age-related OA were investigated in transgenic and control mice using hematoxylin and eosin (H&E) and Safranin O staining. Furthermore, the progression of ACLT-induced OA following adenovirus-mediated HDAC4 overexpression was explored in rats. The expression levels of genes related to hypertrophy, cartilage matrix and its digestion, and chondrocyte proliferation were investigated using qPCR. Immunohistochemistry (IHC) was used to explore the mechanisms underlying HDAC4-controlled age-related changes in OA progression. Results: In human cartilage, we performed morphological analysis and IHC, the results showed that hypertrophy-related structural changes are related to HDAC4 expression. Age-related OA was detected early (OARSI scores 2.7 at 8-month-old) following HDAC4 deletion in 2-month-old mice. Furthermore, qPCR and IHC results showed changes in hypertrophy-related genes Col10a1, Runx2 and Sox9 in chondrocytes, particularly in the expression of Runt-related transcription factor 2 (Runx2, 13.29±0.99 fold). The expression of the main cartilage matrix-related genes Col2a1 and Acan decreased, that of cartilage matrix digestion-related gene MMP-13 increased, while that of chondrocyte proliferation-related genes PTHrP, Ihh and Gli1 changed. In contrast, rat cartilage's qPCR and IHC results showed opposite outcomes after HDAC4 overexpression. Conclusion: Based on the results above, we concluded that HDAC4 expression regulates the onset and development of age-related OA by controlling chondrocyte hypertrophy. These results may help in the development of early diagnosis and treatment of age-related OA.

New Insights From Single-Cell Sequencing Data: Synovial Fibroblasts and Synovial Macrophages in Rheumatoid Arthritis.

Single-cell RNA sequencing (scRNA-seq) technology can analyze the transcriptome expression level of cells with high-throughput from the single cell level, fully show the heterogeneity of cells, and provide a new way for the study of multicellular biological heterogeneity. Synovitis is the pathological basis of rheumatoid arthritis (RA). Synovial fibroblasts (SFs) and synovial macrophages are the core target cells of RA, which results in the destruction of articular cartilage, as well as bone. Recent scRNA-seq technology has made breakthroughs in the differentiation and development of two types of synovial cells, identification of subsets, functional analysis, and new therapeutic targets, which will bring remarkable changes in RA treatment.

Structural elucidation of high-molecular-weight alkaline degradation products of hexoses.

High-molecular-weight alkaline degradation products of hexoses (HMWHADPs) are colored substances in sugar solutions formed during sugar manufacturing process. These products may be occluded within sugar crystals and impart yellow or brown color to sucrose, thereby negatively affecting the quality of white sugar. Thus, the structural properties of HMWHADPs pose a significant scientific problem in the sugar industry. In the present study, the structural properties of HMWHADPs were investigated using nuclear magnetic resonance, zeta potential analyzer, energy-dispersive X-ray spectrometry, ultraviolet-visible spectra, and Fourier transform infrared spectroscopy. Results showed that HMWHADPs mainly contain carboxyl, aldehyde, alcoholic hydroxyl, conjugated double bonds, and saturated alkanes. Possible mechanisms of HMWHADP formation were proposed on the basis of structural property investigation. This study can be used as reference for future research and practice in developing effective methods for the removal of HMWHADPs from sugar solutions and prevention of their further formation in subsequent steps.

Identifying the differentially expressed microRNAs in esophagus squamous cell carcinoma of Kazakh patients in Xinjiang.

Despite improvements in diagnosis and treatment, the survival of patients with advanced stages of esophageal squamous cell carcinoma (ESCC) remains poor. Therefore, novel biomarkers that can assist with early detection of ESCC are required. In the present study, three paired ESCC and normal esophageal tissue samples from Xinjiang Kazakh patients were obtained and microRNA (miRNA) microarray analysis was used to detect the differentially-expressed miRNAs. The target genes of the identified miRNAs were predicted using miRWalk software. A total of 23 miRNAs were differently expressed in Kazakh patients with ESCC. Gene Ontology enrichment analysis demonstrated that the upregulated miRNAs were predominantly associated with the 'vesicle' and 'membrane-bounded vesicle' terms, while the downregulated miRNAs were primarily associated with the term 'negative regulation of integrin-mediated signaling pathway'. The most highly enriched Kyoto Encyclopedia of Genes and Genomes pathway for the differentially-expressed miRNAs was 'Endocrine and other factor-regulated calcium reabsorption'. Protein-protein interaction network analysis revealed that IQ motif containing GTPase activating protein 1, RAB11A, lysine acetyltransferase 2B, catenin α 1 and tight junction protein 2 were hub genes of the network. In conclusion, a number of differentially-expressed miRNAs were identified in ESCC tissues samples from Xinjiang Kazakh patients, which may improve the understanding of the processes of tumorigenesis and development.