Bioinformatic Analysis Identifies Biomarkers and Treatment Targets in Primary Sjögren’s Syndrome Patients with Fatigue

We aim to identify the common genes, biological pathways, and treatment targets for primary Sjögren’s syndrome patients with varying degrees of fatigue features. We select datasets about transcriptomic analyses of primary Sjögren’s syndrome (pSS) patients with different degrees of fatigue features and normal controls in peripheral blood. We identify common differentially expressed genes (DEGs) to find shared pathways and treatment targets for pSS patients with fatigue and design a protein-protein interaction (PPI) network by some practical bioinformatic tools. And hub genes are detected based on the PPI network. We perform biological pathway analysis of common genes by Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Lastly, potential treatment targets for pSS patients with fatigue are found by the Enrichr platform. We discovered that 27 DEGs are identified in pSS patients with fatigue features and the severe fatigued pSS-specific gene is RTP4. DEGs are mainly localized in the mitochondria, endosomes, endoplasmic reticulum, and cytoplasm and are involved in the biological process by which interferon acts on cells and cells defend themselves against viruses. Molecular functions mainly involve the process of RNA synthesis. The DEGs of pSS are involved in the signaling pathways of viruses such as hepatitis C, influenza A, measles, and EBV. Acetohexamide PC3 UP, suloctidil HL60 UP, prenylamine HL60 UP, and chlorophyllin CTD 00000324 are the four most polygenic drug molecules. PSS patients with fatigue features have specific gene regulation, and chlorophyllin may alleviate fatigue symptoms in pSS patients.

Sjogren’s Syndrome: Recent Updates

Primary Sjögren’s syndrome (SS) is a chronic systemic autoimmune disorder affecting primarily perimenopausal women [...]

Immunoregulatory effects of dental mesenchymal stem cells on T and B lymphocyte responses in primary Sjögren's syndrome

Background: In this article, the authors investigate the modulatory effects of dental mesenchymal stem cells (MSCs) on lymphocyte responses in primary Sjögren's syndrome (pSS), which is an autoimmune disease resulting from keratoconjunctivitis sicca and xerostomia. Methods: Mononuclear cells isolated from pSS patients cultured with or without dental MSCs and analyzed for lymphocyte responses via flow cytometry. Results: Dental-follicle (DF)- and dental-pulp (DP)-MSCs downregulated CD4+ T lymphocyte proliferation by increasing Fas-ligand expression on T lymphocytes and FoxP3 expressing Tregs, and decreasing intracellular IFN-γ and IL-17 secretion in pSS patients. DF-MSCs decreased the plasma B cell ratio in the favor of naive B cell population in pSS patients' mononuclear cells. Conclusion: DF- and DP-MSCs can be the new cellular therapeutic candidates for the regulation of immune responses in pSS.

Recent Advances of Salivary Gland Biopsy in Sjögren's Syndrome

Sjögren's syndrome (SS) is a chronic, systemic, inflammatory autoimmune disease characterized by lymphocyte proliferation and progressive damage to exocrine glands. The diagnosis of SS is challenging due to its complicated clinical manifestations and non-specific signs. Salivary gland biopsy plays an important role in the diagnosis of SS, especially with anti-Sjögren's syndrome antigen A (SSA) and anti-SSB antibody negativity. Histopathology based on biopsy has clinical significance for disease stratification and prognosis evaluation, such as risk assessment for the development of non-Hodgkin's lymphoma. Furthermore, histopathological changes of salivary gland may be implicated in evaluating the efficacy of biological agents in SS. In this review, we summarize the histopathological features of salivary gland, the mechanism of histopathological changes and their clinical significance, as well as non-invasive imaging techniques of salivary glands as a potential alternative to salivary gland biopsy in SS.

Integrated Network Pharmacology and Mice Model to Investigate Qing Zao Fang for Treating Sjögren’s Syndrome

Sjögren’s syndrome (SS) is an autoimmune disease, and its conventional treatment has exhibited limited therapeutic efficacy. Qing Zao Fang (QZF), a traditional Chinese medicine formula, is used in the treatment of Sjögren’s syndrome, but its chemical composition is complex, and its pharmacological mechanism is not clear. Therefore, this study aims to explore the potential mechanism of QZF in the treatment of Sjögren’s syndrome based on network pharmacology and SS mouse model. The main active components and predicted targets of QZF were analyzed by network pharmacology. The SS mouse model was constructed and divided into 6 groups: control, SS, SS + hydroxychloroquine (HCQ)-treated, SS + low-dose QZF-treated, SS + medium-dose QZF-treated, and SS + high-dose QZF-treated group. Immunohistochemical, ELISA, and qRT-PCR assays were performed to detect the expressions of targets associated with SS. TUNEL staining was used to detect apoptosis. Cumulatively, 230 active compounds and 1883 targets of QZF were identified. There were 227 common targets for QZF and SS. The effective active ingredients were stigmasterol, neocryptotanshinone II, neotanshinone C, miltionone I, and beta-pinene. It mainly acts on biological processes such as inflammatory response, chemokine metabolic process, and immune response as well as pathways such as FoxO signaling pathway, Yersinia infection, HIF-1 signaling pathway, and TNF signaling pathway. In SS mice, levels of AKT1, HIF-1α, TNF-α, IL-6, and IL-17A were increased, while decreased after QZF treatment. In contrast, IL-10 levels were decreased in SS mice and increased in QZF-treated mice. In addition, QZF reduced apoptosis in the submandibular gland tissue compared to SS mice. It can be concluded that the QZF in treatment of SS is the result of the combined action of multiple components, multiple targets, and multiple pathways. This study improves the understanding of the link between QZF and SS on molecular mechanisms.