Polydatin Alleviates Diabetes-Induced Hyposalivation through Anti-Glycation Activity in db/db Mouse

Polydatin (resveratrol-3-O-β-mono-D-glucoside) is a polyphenol that can be easily accessed from peanuts, grapes, and red wine, and is known to have antiglycation, antioxidant, and anti-inflammatory effects. Diabetes mellitus is a very common disease, and diabetic complications are very common complications. The dry mouth symptom is one of the most common oral complaints in patients with diabetes mellitus. Diabetes mellitus is thought to promote hyposalivation. In this study, we aimed to investigate the improvement effect of polydatin on diabetes-induced hyposalivation in db/db mouse model of type 2 diabetes. We examined salivary flow rate, TUNEL assay, PAS staining, and immunohistochemical staining for AGEs, RAGE, HMGB1, 8-OHdG, and AQP5 to evaluate the efficacy of polydatin in the submandibular salivary gland. Diabetic db/db mice had a decreased salivary flow rate and salivary gland weight. The salivary gland of the vehicle-treated db/db mice showed an increased apoptotic cell injury. The AGEs were highly accumulated, and its receptor, RAGE expression was also enhanced. Expressions of HMGB1, an oxidative cell damage marker, and 8-OHdG, an oxidative DNA damage marker, increased greatly. However, polydatin ameliorated this hypofunction of the salivary gland and inhibited diabetes-related salivary cell injury. Furthermore, polydatin improved mucin accumulation, which is used as a damage marker for salivary gland acinar cells, and decreased expression of water channel AQP5 was improved by polydatin. In conclusion, polydatin has a potent protective effect on diabetes-related salivary gland hypofunction through its antioxidant and anti-glycation activities, and its AQP5 upregulation. This result suggests the possibility of the use of polydatin as a therapeutic drug to improve hyposalivation caused by diabetes.

PDFGRα+ Stromal Cells Promote Salivary Gland Proacinar Differentiation Through FGF2-dependent BMP7 Signaling.

Stromal cells can direct epithelial differentiation during organ development; however, these pathways remain poorly defined. FGF signaling is essential for submandibular salivary gland development, and FGF2 can regulate proacinar cell differentiation in organoids through autocrine signaling in stromal cells. We performed scRNA Seq and identified stromal cell subsets expressing Fgf2 and Fgf10 that also express Pdgfrα. When combined with epithelial cells in organoids, MACS-sorted PDGFRα+ cells sufficiently promoted proacinar differentiation. Gene expression analysis revealed FGF2 activates the gene Bmp7 in the stroma. BMP7 could replace stromal signaling and stimulate epithelial acinar differentiation but not branching. However, in the absence of FGF2, pathway analysis revealed that the stromal cells differentiated into myofibroblasts. Myofibroblast differentiation was induced when we treated organoids with TGFβ1, which also prevented proacinar differentiation. Conversely, FGF2 reversed TGFβ's effects. Dissecting pathways driving acinar differentiation will facilitate development of regenerative therapies.

Exosomes Derived from Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSC) Protect Submandibular Glands in Diabetic Rats

Our study assess whether exosomes derived from bone marrow mesenchymal stem cells (BM-MSC) ameliorates diabetic salivary gland complications. 10 SD rats were assigned into diabetes group I and exosome treatment group II. Diabetic rats were induced by streptozotocin (STZ) and injected with DMSO or exosomes through tail vein followed by collection of submandibular salivary gland samples for histological analysis and TGFβ, Smad2 and Smad3 level by PCR, saliva IgA and serum amylase level. Compared with control mice, exosome treatment mice showed less fibrosis of the submandibular salivary glands and duct components with a more complete structure. Exosome treatment inhibited TGFβ, Smad2 and Smad3 level to reduce diabetic salivary gland complications, effectively decreased blood sugar level, improved salivary glands function with significantly reduced serum amylase and salivary IgA levels. In conclusion, BM-MSC-derived exosomes may be a new therapeutic strategy for treating diabetic salivary gland complications.

Sialotripsy as a treatment option for patients with salivary stone disease

Background. The pathologies of the salivary glands are very diverse. Salivary stone disease occupies a special place among diseases of the salivary glands of a non-neoplastic nature. The incidence of salivary stone disease is extremely extensive and accounts for up to 85% of all pathologies of the salivary glands.Objective. Improvement of minimally invasive methods of treatment of salivary stone disease, which does not lead to excision of the gland.Material and methods. On the basis of the Clinics of the Samara State Medical University of the Ministry of Health of Russia, in the period from 2010 to 2020, a clinical group was formed, consisting of 193 patients with salivary stone disease of various localization. The age of the patients ranged from 16 to 84 years. All patients were therapeutically examined at the preoperative stage, voluntary informed consent was signed. Shockwave sialotripsy was performed in 95 patients of the main group (in 64 patients the calculus was located in the submandibular salivary gland, in 31 patients – in the parotid salivary gland). For lithotripsy, we used a lithotripter apparatus "Edap" (France) and "Wolf" (Germany).Results. The analysis of the results obtained as a result of the study made it possible to draw a conclusion about reasonably better results of removal of calculi in the ducts of the salivary glands using the lithotripter "Swiss LithoClast® Master" (Switzerland). At the first visit and the therapeutic effect of the lithotripter, all patients suffering from bouts of salivary colic showed complete cessation.Conclusion. Thus our study, which was devoted to the study of the results of various methods of treating patients with salivary stone disease showed that sialolithotripsy using special narrowly targeted devices for crushing and subsequent excretion of salivary calculi allows to achieve the best results at present.

Suspected IgG4-related disease of the submandibular salivary gland and periorbital soft tissue in a man with latent tuberculosis

A 77-year-old Lithuanian man presented to our institution with recurrent episodes of periorbital cellulitis, submandibular swelling and sialadenitis. Investigations revealed a positive QuantiFERON, raised inflammatory markers and normal autoimmune screen. Cross-sectional imaging showed no signs of occult malignancy, and work-up for mycobacterial infection including imaging and bronchoalveolar lavage did not show active tuberculosis. During hospitalisation, the patient developed fevers of unknown origin, which were investigated with a positron emission tomography (PET) scan and a bone marrow aspiration, without evidence of occult infection or malignancy. Serum IgG4 level was three times the upper limit of normal. The patient responded well to oral steroids but relapsed after completing a slow taper. Serum IgG4 level was three times the upper limit of normal. He had an American College of Rheumatology/European League Against Rheumatism score of 20, in conjunction with involvement of orbital and salivary tissue. Therefore, IgG4-related disease was considered the most likely diagnosis, despite prominent fevers, which are among the exclusion criteria for this diagnosis. After a multidisciplinary review including rheumatology and ophthalmology, the patient was commenced on maintenance methotrexate with remission of symptoms.