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Objective: In this study, we sought to determine the expression profiles of long non‐coding RNAs (lncRNAs) and messenger RNAs (mRNAs) and construct functional networks to analyze their potential roles following botulinum toxin type A (BTXA)‐mediated inhibition of salivary secretion. Methods: The submandibular gland of rats in the BTXA and control groups was injected with BTXA and saline, respectively. Microarray analysis was used to identify the differentially expressed lncRNAs and mRNAs. Gene ontology and pathway analysis were performed to examine the biological functions. Functional networks, including lncRNA‐mRNA co‐expression and competing endogenous RNA (ceRNA) networks, were constructed to reveal the interaction between the coding and non‐coding genes. Results: Microarray analysis revealed that 254 lncRNAs and 631 mRNAs were differentially expressed between the BTXA and control groups. Bioinformatic analysis revealed that most of the mRNAs were closely related to transmembrane transporter activity. lncRNA‐mRNA co‐expression and ceRNA networks were constructed, and several critical mRNA‐lncRNA axes and key microRNAs related to salivary secretion were identified. Conclusions: Our study identified differentially expressed lncRNAs and mRNAs through microarray analysis and explored the interactions between the coding and non‐coding genes through bioinformatic analysis. These findings provide new insights into the mechanism of BTXA‐mediated inhibition of salivary secretion. [ABSTRACT FROM AUTHOR]

Diabetes is often accompanied by dysfunction of salivary glands. However, the molecular mechanism remains unclear. The mechanisms that underlie diabetic hyposalivation were studied by db/db mice and SMG‐C6 cells. We found morphological changes and decreased stimulated salivary flow rates of the submandibular gland (SMG) in diabetic mice. We observed structural changes and dysfunction of mitochondria. More mitophagosomes and higher expression of autophagy‐related proteins were detected. Increased levels of proteins PINK1 and Parkin indicate that PINK1/Parkin‐mediated mitophagy was activated in diabetic SMG. Consistently, high glucose (HG) induced mitochondrial dysfunction and PINK1/Parkin‐mediated mitophagy in cultivated SMG‐C6 cells. HG also increased reactive oxygen species (ROS) and lessened activation of antioxidants in SMG‐C6 cells. In addition, HG lowered ERK1/2 phosphorylation and HG‐induced mitophagy was decreased after ERK1/2 was activated by LM22B‐10. Altogether, these data suggest that ROS played a crucial role in diabetes‐induced mitochondrial dysfunction and PINK1/Parkin‐mediated mitophagy and ERK1/2 was required in HG‐induced mitophagy in SMG. [ABSTRACT FROM AUTHOR]

The current mechanism by which aging reduces salivary secretion is unknown. This study investigates the mechanism of aging-related submandibular (SMG) dysfunction and evaluates the therapeutic potential of dental pulp stem cell-derived exosomes (DPSC-exos). We found that the stimulated salivary flow rate was significantly reduced in naturally aging and D-galactose-induced aging mice (D-gal mice) compared to control mice. Acinar atrophy and periductal fibrosis in SMGs and parotid glands (PGs) were observed in naturally aging and D-gal mice, whereas sublingual glands (SLGs) had no notable alterations. We observed the accumulation of senescent cells in the SMGs, along with a decrease in claudin-3 (Cldn-3) expression and alterations in the distribution of Cldn1 and Cldn3. Additionally, after D-gal-induced senescence of SMG-C6 cells, there was a decrease in paracellular pathway permeability, reduced expression of Cldn3 and occludin, and changes in the distribution of Cldn1, 3, 4, and 7. Furthermore, injecting DPSC-exos into the SMGs of D-gal mice improved stimulated salivary flow rate, reduced acinar atrophy, and decreased SA-β-gal activity. Our study identified that increased senescence of SMGs in aging mice can cause a decrease in salivary secretion by disrupting the expression and distribution of tight junction molecules, and injection of DPSC-exos ameliorates SMG secretory dysfunction. These findings may provide new clues to novel therapeutic targets for aging-related dysfunction of SMGs., (© 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Sepsis is an uncontrolled systemic inflammatory response. Long noncoding RNAs (lncRNAs) are involved in the pathogenesis of sepsis. However, little is known about the roles of lncRNAs in sepsis-induced myocardial dysfunction., Objective: We aimed to determine the regulatory mechanism of lncRNAs in sepsis-induced myocardial dysfunction., Methods: In this study, we analysed the lncRNA and mRNA expression profiles using microarray analysis. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction network, and gene set enrichment analysis were used to evaluate the data. We also constructed coding and noncoding coexpression and competing endogenous RNA networks to investigate the mechanisms., Results: In vivo lipopolysaccharide -induced sepsis rat model was established. A total of 387 lncRNAs and 1,952 mRNAs were identified as significantly changed in the left ventricle. Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs showed that the upregulated genes were mainly enriched in the "complement and coagulation cascade pathway" and "immune-related biological processes" terms. Eight significantly changed lncRNAs detected by RT-qPCR may be responsible for these processes. A competing endogenous RNA network was generated, and the results indicated that eight lncRNAs were related to the "calcium ion binding" process., Conclusion: These results demonstrate that crosstalk between lncRNAs and mRNAs may play important roles in the development of sepsis-induced myocardial dysfunction., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (© 2022 Bentham Science Publishers.)

Sepsis is the leading cause of death in hospital intensive care units. In light of recent studies showing that variations in N 6 -methyladenosine (m 6 A) levels in different RNA transcripts influence inflammatory responses, we evaluated the m 6 A profiles of rat aortic mRNAs and lncRNAs after lipopolysaccharide (LPS)-induced sepsis. LC-MS-based mRNA modification analysis showed that global m6A levels were significantly decreased in aortic tissue of rats injected intraperitoneally with LPS. This finding was consistent with downregulated expression of METTL3 and WTAP, two members of the m 6 A writer complex, in LPS-exposed aortas. Microarray analysis of m 6 A methylation indicated that 40 transcripts (31 mRNAs and 9 lncRNAs) were hypermethylated, while 223 transcripts (156 mRNAs and 67 lncRNAs) were hypomethylated, in aortic tissue from LPS-treated rats. On GO and KEGG analyses, 'complement and coagulation cascades', 'transient receptor potential channels', and 'organic anion transmembrane transporter activity' were the major biological processes modulated by the differentially m 6 A methylated mRNAs. In turn, competing endogenous RNA network analysis suggested that decreased m 6 A levels in lncRNA-XR_343955 may affect the inflammatory response through the cell adhesion molecule pathway. Our data suggest that therapeutic modulation of the cellular m 6 A machinery may be useful to preserve vascular integrity and function during sepsis.

Hypertension is a systemic disorder that affects numerous physiological processes throughout the body. Improper sodium transport is a common comorbidity of hypertension, and sodium transport is also critical for maintaining the secretion of submandibular glands, whether the function of submandibular glands is affected by hypertension remains unclear. To determine whether hypertension induces changes in the protein expression of submandibular glands, we compared the proteome of submandibular glands from 14-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats using LC-MS/MS. The results revealed that 95 proteins displayed different levels of expression between the submandibular glands from the SHRs and WKYs. Among these, 35 proteins were more abundant, and 60 proteins were less abundant in the SHR compared with the WKY rats. Specifically, aquaporin 5 and parvalbumin, which are correlated with water transport and intracellular Ca 2+ signal transduction, were verified to exhibit differences in protein abundance. Impaired Ca 2+ response to carbachol was confirmed in the acinar cells from SHRs, and hyposecretion by the submandibular glands was further confirmed by in vivo saliva collection. In conclusion, the proteomic analysis of the submandibular glands of SHRs revealed novel changes in protein abundance that provides possible mechanisms connecting hypertension and hyposecretion in submandibular glands.

Sjögren's syndrome is a chronic autoimmune disease, the pathogenesis of which still remains to be explored. Non-obese diabetic (NOD) mouse, presenting impairment of secretory function as well as the development of sialoadenitis, which is in common with human Sjögren's syndrome, is considered as one of the appropriate animal models for the study of Sjögren's syndrome. With regard to genetic factors, apoptosis, autoantibodies and cytokines, this paper reviewed the progress in understanding the pathogenesis of Sjögren's syndrome in NOD mice.