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Pharmaceutical Biology Dec 2023Zengye decoction (ZYD) has been considered to have a curative effect on Sjogren's syndrome (SS). However, its therapeutic mechanisms remain obscure.
CONTEXT
Zengye decoction (ZYD) has been considered to have a curative effect on Sjogren's syndrome (SS). However, its therapeutic mechanisms remain obscure.
OBJECTIVES
This research explores the mechanisms of ZYD against SS.
MATERIALS AND METHODS
The active compounds and targets of ZYD were searched in the TCMSP and BATMAN-TCM databases. SS-related targets were obtained from the GeneCards database. The GO and KEGG enrichment analyses elucidated the molecular mechanisms. Animal experiments were performed using 8 C57BL/6 mice that served as the control group (physiological saline treatment) and 16 NOD mice randomly divided into the model group (physiological saline treatment) and the ZYD group (ZYD treatment) for 8 weeks to verify the therapeutic effects of ZYD on SS.
RESULTS
Twenty-nine active compounds with 313 targets of ZYD and 1038 SS-related targets were screened. Thirty-two common targets were identified. β-Sitosterol and stigmasterol might be important components. GO analysis suggested that the action of ZYD against SS mainly involved oxidative stress, apoptotic processes, and tumor necrosis factor receptor superfamily binding, etc. KEGG analysis indicated the most significant signaling pathway was apoptosis-multiple species. Animal experiments showed that ZYD improved lymphocytic infiltration of the submandibular glands (SMGs), reduced the serum levels of TNF-α, IL-1β, IL-6, and IL-17, upregulated the expression of Bcl-2, and downregulated the expression of Bax and Caspase-3 in the model mice.
DISCUSSION AND CONCLUSION
ZYD has anti-inflammatory and anti-apoptotic effects on SS, which provides a theoretical basis for the treatment of SS with ZYD.
Topics: Animals; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Animal Experimentation; Network Pharmacology; Sjogren's Syndrome
PubMed: 37606264
DOI: 10.1080/13880209.2023.2248188 -
Cureus Sep 2023In strict accordance with PRISMA 2020 guidelines, our research team conducted a comprehensive systematic literature review (SLR) to explore the treatment and preventive... (Review)
Review
In strict accordance with PRISMA 2020 guidelines, our research team conducted a comprehensive systematic literature review (SLR) to explore the treatment and preventive strategies for Sjögren's Syndrome (SS). Leveraging a meticulous search strategy, we scoured reputable databases such as PubMed, PubMed Central, Google Scholar, Web of Science, and The Cochrane Library. Our analysis zeroed in on 10 seminal articles that met our stringent inclusion criteria, providing a holistic view of the existing treatment landscape for SS, along with emerging diagnostic tools and associated biomarkers indicative of lymphoma risk. From a clinical standpoint, our findings unequivocally highlight the detrimental effects of SS on patients' overall well-being. Of particular interest is the growing body of evidence that underscores the effectiveness of natural remedies and over-the-counter supplements rich in antioxidants as viable therapeutic interventions. Contrary to expectations, no single laboratory marker emerged as highly sensitive for the diagnosis of SS. On a promising note, dental implants have been demonstrated to offer lasting benefits with minimal side effects, emphasizing their potential utility in enhancing the oral health of individuals affected by SS. Given the evolving nature of treatment approaches for SS, our review strongly calls for further investigations. Such research endeavors are imperative for validating the effectiveness of these treatment options, whether they serve as primary or preventive care solutions, with the overarching aim of improving the quality of oral health among those suffering from SS.
PubMed: 37872910
DOI: 10.7759/cureus.45751 -
MedRxiv : the Preprint Server For... Dec 2023Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic...
OBJECTIVES
Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS.
METHODS
We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases.
RESULTS
We revealed genetic associations with PAPS in a regulatory locus within the HLA class II region near and in with a genome-wide level of significance. 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele in the HLA class II locus is associated with overexpression of , , , and , and is independent of the association between PAPS and . Functional analyses highlighted immune and nervous system related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren's syndrome, suggesting colocalized causal variations close to , , and .
CONCLUSIONS
This study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.
PubMed: 38405993
DOI: 10.1101/2023.12.05.23299396 -
Chinese Medical Journal Nov 2023Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed...
BACKGROUND
Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth (SHED-exos) in sialadenitis caused by SS.
METHODS
SHED-exos were administered to the submandibular glands (SMGs) of 14-week-old non-obese diabetic (NOD) mice, an animal model of the clinical phase of SS, by local injection or intraductal infusion. The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice. Protein expression was examined by western blot analysis. Exosomal microRNA (miRNAs) were identified by microarray analysis. Paracellular permeability was evaluated by transepithelial electrical resistance measurement.
RESULTS
SHED-exos were injected into the SMG of NOD mice and increased saliva secretion. The injected SHED-exos were taken up by glandular epithelial cells, and further increased paracellular permeability mediated by zonula occluden-1 (ZO-1). A total of 180 exosomal miRNAs were identified from SHED-exos, and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway might play an important role. SHED-exos treatment down-regulated phospho-Akt (p-Akt)/Akt, phospho-glycogen synthase kinase 3β (p-GSK-3β)/GSK-3β, and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells. Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1, a PI3K agonist. Slug bound to the ZO-1 promoter and suppressed its expression. For safer and more effective clinical application, SHED-exos were intraductally infused into the SMGs of NOD mice, and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and Slug and increased ZO-1 expression.
CONCLUSION
Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3β/Slug pathway-mediated ZO-1 expression.
Topics: Mice; Animals; Humans; Sjogren's Syndrome; Proto-Oncogene Proteins c-akt; Tight Junctions; Glycogen Synthase Kinase 3 beta; Mice, Inbred NOD; Phosphatidylinositol 3-Kinases; Exosomes; Xerostomia; Phosphatidylinositol 3-Kinase; MicroRNAs
PubMed: 37052137
DOI: 10.1097/CM9.0000000000002610 -
Neural Regeneration Research Jan 2024Corneal neuromas, also termed microneuromas, refer to microscopic, irregularly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.... (Review)
Review
Corneal neuromas, also termed microneuromas, refer to microscopic, irregularly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury. The formation of corneal neuromas results from damage to corneal nerves, such as following corneal pathology or corneal or intraocular surgeries. Initially, denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers, and later injured axons regenerate and new sprouts called neuromas develop. In recent years, analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy, a non-invasive imaging technique with microscopic resolution, has been used to evaluate corneal neuropathy and ocular surface dysfunction. Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes, and are a promising surrogate biomarker for ocular surface diseases, such as neuropathic corneal pain, dry eye disease, diabetic corneal neuropathy, neurotrophic keratopathy, Sjögren's syndrome, bullous keratopathy, post-refractive surgery, and others. In this review, we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas, as well as elaborated on their pathogenesis, visualization via in vivo confocal microscopy, and utility in monitoring treatment efficacy. As current quantitative analysis on neuromas mainly relies on manual annotation and quantification, which is user-dependent and labor-intensive, future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner, allowing it to be applied in clinical settings more efficiently. Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.
PubMed: 37488855
DOI: 10.4103/1673-5374.375308 -
Pediatric Rheumatology Online Journal Oct 2023Sjögren's syndrome (SS) is a rare disease with unclear diagnostic criteria among the children and adolescents. The purpose of this study is to describe the clinical...
OBJECTIVE
Sjögren's syndrome (SS) is a rare disease with unclear diagnostic criteria among the children and adolescents. The purpose of this study is to describe the clinical features of pediatric Sjögren's syndrome and validate with Japanese diagnostic guidelines criteria of 2018.
METHODS
We conducted a retrospective analysis of the clinical data of a cohort of 54 patients with pediatric Sjögren's syndrome admitted to our hospital over a total of 10 years from September 2013 to September 2022.
RESULTS
The ratio of females to males was 49:5 among the 54 children (34 cases of primary SS and 20 cases of secondary SS), the average age of onset of symptoms for the first time was 9.9 years, and the average age at diagnosis was 10.2 years. In terms of subjective symptoms, 7 cases (13.0%) presented with dry mouth and 5 cases (9.3%) reported dry eyes. The positive rates were 9.3% for Schirmer I test, 70.4% for salivary gland function test, and 55.6% for salivary gland ultrasonography. The positive rates were 94.4% for Anti-Ro/SSA antibodies, 66.7% for Anti-La/SSB antibodies, 88.9% for ANA, 59.3% for RF, and the elevation rate of IgG was 63.0%. Among the EULAR Sjögren's syndrome disease activity index (ESSDAI) domains, the biological, constitutional, glandular, cutaneous, and lymphadenopathy domains were most involved. Treatment consisted of glucocorticoids in 88.9% of the patients in our study and hydroxychloroquine in 92.6%. As per the Japanese version of the clinical practice guidance for Sjögren's Syndrome in pediatric patients (2018), 5 cases were identified as Definite SS, 35 cases as Probable SS, and 14 cases as Possible SS. With respect to primary and secondary SS, there was essentially no significant difference between the groups in any of the above aspects.
CONCLUSIONS
Patients with pediatric SS presented with a wide spectrum of clinical features, a low prevalence of reported symptoms of dry mouth and dry eyes, and various clinical manifestations with multi-system involvement. These are similar to other pediatric study cohorts in terms of epidemiology, auxiliary investigation results, disease activity scores, and treatment. The coincidence between our study and the Japanese version of the clinical practice guidance for Sjögren's Syndrome in pediatric patients (2018) is good for the diagnosis of pediatric SS.
Topics: Male; Female; Adolescent; Humans; Child; Sjogren's Syndrome; Retrospective Studies; Salivary Glands; Dry Eye Syndromes
PubMed: 37833819
DOI: 10.1186/s12969-023-00902-y -
Journal of Otolaryngology - Head & Neck... Aug 2023Juvenile recurrent parotitis (JRP) is characterized by recurrent episodes of painful parotid swelling in children. The purpose of this systematic review was to determine... (Review)
Review
BACKGROUND
Juvenile recurrent parotitis (JRP) is characterized by recurrent episodes of painful parotid swelling in children. The purpose of this systematic review was to determine the diagnostic and therapeutic effectiveness of sialendoscopy in children affected by JRP.
METHODS
A systematic literature search was performed in PubMed, EMBASE, Scopus and the Cochrane Library until April 2022, without language restrictions or specified start date. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS).
RESULTS
Our review included 524 patients and 646 sialendoscopies. The sample sizes of the different studies ranged from 3 to 77 subjects. Most authors performed sialendoscopy under general anesthesia. The mean percentage of recurrences observed was 25.1% (95% confidence intervals) (CI 23.6-26.6). There was a statistically significant relationship between the number of attacks/year and recurrences (p < 0.05). The percentage of recurrences according to the type of irrigation/flushing used ranged from 22.2% to 25.2%, with no significant differences between the use of corticosteroids alone (25.2% of recurrences), corticosteroids plus antibiotics (25% of recurrences) or saline alone (22.2% of recurrences). Sialoendoscopy has proved in all cases to be a valid method for the diagnosis of JRP, but it does not allow a reliable differential diagnosis with other autoimmune parotitis such as Sjögren's syndrome.
CONCLUSION
According to our results, parotid sialoendoscopy was 74.9% effective as a primary treatment in the prevention of recurrent symptoms in JRP. The type of ductal irrigation used did not significantly influence the prognostic outcome.
Topics: Child; Humans; Parotitis; Parotid Gland; Anesthesia, General; Recurrence
PubMed: 37598195
DOI: 10.1186/s40463-023-00658-1 -
Molecules (Basel, Switzerland) Aug 2023Sjögren's disease (SjD) is the second most prevalent autoimmune disorder that involves chronic inflammation of exocrine glands. Correct diagnosis of primary SjD (pSjD)...
Sjögren's disease (SjD) is the second most prevalent autoimmune disorder that involves chronic inflammation of exocrine glands. Correct diagnosis of primary SjD (pSjD) can span over many years since disease symptoms manifest only in advanced stages of salivary and lachrymal glandular destruction, and consensus diagnostic methods have critical sensitivity and selectivity limitations. Using nuclear magnetic resonance (NMR) spectroscopy, we determined the composition of metabolites in unstimulated saliva samples from 30 pSjD subjects and 30 participants who do not have Sjögren's disease (non-Sjögren's control group, NS-C). Thirty-four metabolites were quantified in each sample, and analysis was conducted on both non-normalized (concentration) and normalized metabolomics data from all study participants (ages 23-78) and on an age-restricted subset of the data (ages 30-70) while applying false discovery rate correction in determining data significance. The normalized data of saliva samples from all study participants, and of the age-restricted subset, indicated significant increases in the levels of glucose, glycerol, taurine, and lactate, as well as significant decreases in the levels of 5-aminopentanoate, acetate, butyrate and propionate, in subjects with pSjD compared to subjects in the NS-C group. Additionally, a significant increase in choline was found only in the age-restricted subset, and a significant decrease in fucose was found only in the whole study population in normalized data of saliva samples from the pSjD group compared to the NS-C group. Metabolite concentration data of saliva samples from all study participants, but not from the age-restricted subset, indicated significant increases in the levels of glucose, glycerol, taurine, and lactate in subjects with pSjD compared to controls. The study showed that NMR metabolomics can be implemented in defining salivary metabolic signatures that are associated with disease status, and can contribute to differential analysis between subjects with pSjD and those who are not affected with this disease, in the clinic.
Topics: Humans; Saliva; Glycerol; Sjogren's Syndrome; Autoimmune Diseases; Lactates
PubMed: 37570863
DOI: 10.3390/molecules28155891 -
Health Science Reports Oct 2023Atherosclerosis (AS) risk increases in patients with systemic autoimmune diseases. The association and mechanism between primary Sjogren's syndrome (pSS) and AS haven't...
BACKGROUND AND AIMS
Atherosclerosis (AS) risk increases in patients with systemic autoimmune diseases. The association and mechanism between primary Sjogren's syndrome (pSS) and AS haven't been explained for now. We did this cross-sectional study to clarify the prevalence and risk factors of AS in patients with pSS, and to further explore how immune cells and inflammatory cytokines work in the process.
METHODS
Patients with pSS were enrolled. General information, AS events, immune cells, inflammatory cytokines, and related clinical data were recorded. Prevalence of AS events was calculated. Correlation analysis between immune factors and AS quantitative parameters were conducted by SPSS v20.0.
RESULTS
A total of 155 pSS patients were included with a median Framingham 10-year risk of 7%. Sixty-four AS events were recorded, with a prevalence of 41.3%. Carotid intima-media thickness was positively correlated to immunoglobulin (Ig) A ( = 0.245, = 0.030) and negatively correlated to IgM ( = -0.227, = 0.045). Left ankle-brachial pulse wave velocity (baPWV) was positively correlated to the course of disease ( = 0.352, = 0.004), B cells ( = 0.410, = 0.001), and T helper (Th) cells ( = 0.284, = 0.029), while negatively correlated to IgM ( = -0.257, = 0.042). Right baPWV was positively correlated to the course of pSS ( = 0.319, = 0.010), B cells ( = 0.453, < 0.001), Th cells ( = 0.302, = 0.020), and C-reactive protein (CRP) ( = 0.286, = 0.042). Use of hydroxychloroquine, cyclophosphamide, and glucocorticoids had no impact on AS events.
CONCLUSION
The prevalence of AS in patients with pSS is reported to be 41.3%. Several risk factors have been associated with AS in these patients, including the duration of the disease, levels of Th cells, B lymphocytes, and CRP. Interestingly, IgM appears to have a protective effect against AS. It is worth noting that traditional therapy for pSS does not seem to have any effect in preventing AS events.
PubMed: 37885467
DOI: 10.1002/hsr2.1638 -
Non-Coding RNA in Salivary Extracellular Vesicles: A New Frontier in Sjögren's Syndrome Diagnostics?International Journal of Molecular... Aug 2023Sjögren's syndrome is an autoimmune rheumatic disease characterized by inflammation of the salivary and lacrimal glands, often manifesting as dry mouth and dry eyes. To...
Sjögren's syndrome is an autoimmune rheumatic disease characterized by inflammation of the salivary and lacrimal glands, often manifesting as dry mouth and dry eyes. To simplify diagnostics of primary Sjögren's syndrome (pSS), a non-invasive marker is needed. The aim of the study was to compare the RNA content of salivary extracellular vesicles (EVs) between patients with pSS and healthy controls using microarray technology. Stimulated whole saliva was collected from 11 pSS patients and 11 age-matched controls. EV-RNA was isolated from the saliva samples using a Qiagen exoRNeasy Midi Kit and analyzed using Affymetrix Clariom D™ microarrays. A one-way ANOVA test was used to compare the mean signal values of each transcript between the two groups. A total of 9307 transcripts, coding and non-coding RNA, were detected in all samples. Of these transcripts, 1475 showed statistically significant differential abundance between the pSS and the control groups, generating two distinct EV-RNA patterns. In particular, tRNAs were downregulated in pSS patients, with the transcript tRNA-Ile-AAT-2-1 showing a 2-fold difference, and a promise as a potential biomarker candidate. This study therein demonstrates the potential for using salivary EV-RNA in pSS diagnostics.
Topics: Humans; Sjogren's Syndrome; Keratoconjunctivitis Sicca; Autoimmune Diseases; Extracellular Vesicles; RNA; RNA, Untranslated
PubMed: 37686214
DOI: 10.3390/ijms241713409