Uncovering potential new biomarkers and immune infiltration characteristics in primary Sjögren's syndrome by integrated bioinformatics analysis.

Primary Sjögren's syndrome (pSS) is known as autoimmune disease characterized by damage to endocrine glands, such as the salivary and lacrimal glands. This study aimed to identify potential biomarkers for pSS using integrated bioinformatics analysis and explore the relationship between differentially expressed genes (DEGs) and immune infiltration. Three pSS datasets (GSE7451, GSE23117, and GSE40611) from the gene expression omnibus database were integrated. All the datasets were processed in R (version 4.0.3). A total of 16 immune cells and 13 immune functions were obtained. The top immune cell and immune function were "activated" dendritic cells and major histocompatibility complex class I. Correlation analysis showed the top correlation among 16 immune cells were B cells and tumor infiltrating lymphocytes, check-point and T cell co-stimulation, respectively. In comparisons of immune score, "activated" dendritic cells (.657 vs 594, P < .001), B cells (.492 vs 434, P = .004), macrophages (.631 vs 601, P = .010), inflammation-promoting (.545 vs 478, P < .001), Type I interferon Reponse (.728 vs 625, P < .001) and so on were higher in pSS than control group. In correlation analysis, the up-regulation of interferon induced protein with tetratricopeptide repeats 1 gene was strongly correlated with Type I interferon response with a correlation coefficient of .87. The receiver operating characteristic curve of 5 genes showed that the area under curve was.891. In the verification model, the area under curve was.881. In addition, disease ontology analysis supported the association between DEGs and pSS. In summary, pSS has a variety of DEGs in immune infiltration, which is worthy of the attention from clinicians.

TPP1 Inhibits DNA Damage Response and Chemosensitivity in Esophageal Cancer.

TPP1, as one of the telomere-protective protein complex, functions to maintain telomere stability. In this study, we found that TPP1 was significantly upregulated in esophageal cancer (EC). We found that the proliferation and migration ability were significantly inhibited, while the results of flow cytometry assay indicated that the growth was hindered in the G1 phase after TPP1 knockdown. However, the proliferative viability and migratory ability were reversed after TPP1 overexpression in EC cells. Then, we found a significant increase in ß-galactosidase positivity following TPP1 knockdown and the opposite following TPP1 overexpression in EC cells. Furthermore, TPP1 knockdown increased DNA damage and upregulated expression of the γ-H2AXS139 in the cell nucleus. Correspondingly, DNA damage was reversed after TPP1 overexpression in EC cells. Similarly, we found that the expression of ATM/ATR pathway proteins were upregulated after TPP1 knockdown, while the expression of the above proteins was downregulated after TPP1 overexpression in EC cells. TPP1 knockdown significantly inhibited the growth of transplanted tumors and upregulated the expression of ATM/ATR pathway proteins in transplanted tissues, whereas TPP1 overexpression significantly promoted their proliferation and downregulated the expression of the above proteins in vivo. Strikingly, we found that TPP1 could reduce the chemosensitivity of EC cells to cisplatin, which may have a potential link to clinical chemoresistance. In conclusion, TPP1 regulates the DNA damage response through the ATM/ATR-p53 signaling pathway and chemoresistance and may be a new target for improving the efficacy of chemotherapy in the treatment of EC.

Bioinformatics analysis identified immune infiltration, risk and drug prediction models of copper-induced death genes involved in salivary glands damage of primary Sjögren's syndrome.

This study aimed to identify copper-induced death genes in primary Sjögren's syndrome (pSS) and explore immune infiltration, risk and drug prediction models for salivary glands (SGs) damage. The 3 datasets, including GSE40611, GSE23117, and GSE7451 from the Gene Expression Omnibus database were downloaded. The datasets were processed using the affy in R (version 4.0.3). In immune cells, copper-induced death genes were strongly expressed in "activated" dendritic cells (aDCs), macrophages and regulatory T cells (Treg). In immune functions, copper-induced death genes were strongly expressed in major histocompatibility complex (MHC) class I, human leukocyte antigen (HLA) and type I interferon (IFN) response. Correlation analysis showed that 5 genes including SLC31A1, PDHA1, DLD, ATP7B, and ATP7A were significantly correlated with immune infiltration. The nomogram suggested that the low expression of PDHA1 was significant for predicting the risk of pSS and the area under curve was 0.678. Drug model suggested that "Bathocuproine disulfonate CTD 00001350," "Vitinoin CTD 00007069," and "Resveratrol CTD 00002483" were the drugs most strongly associated with copper-induced death genes. In summary, copper-induced death genes are associated with SGs injury in pSS, which is worthy of clinicians' attention.