Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Autologous submandibular gland (SMG) transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously. This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients' glands 4-6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.
Animals ; Autonomic Pathways ; growth & development ; Fascia ; innervation ; Female ; Humans ; Keratoconjunctivitis Sicca ; surgery ; Male ; Models, Animal ; Rabbits ; Recovery of Function ; Secretory Rate ; Submandibular Gland ; innervation ; transplantation ; Transplantation, Autologous

Objective:To investigate the distribution and drug resistance of anaerobic bacteria in the patients with oral and maxillofacial infection.Methods:Aerobic and anaerobic bacteria cultures from 61 specimens of pus from the patients with oral and maxillofacial infection in the Department of Oral and Maxillofacial Surgery,Peking University School of Stomatology were identified.The culture type was evaluated by API 20A kit and drug resistance test was performed by Etest method.The clinical data and antibacterial agents for the treatment of the 61 cases were collected,and the final outcomes were recor-ded.Results:The bacteria cultures were isolated from all the specimens,with aerobic bacteria only in 6 cases (9 .8%),anaerobic bacteria only in 7 cases (1 1 .5%),and both aerobic and anaerobic bacteria in 48 cases (78.7%).There were 55 infected cases (90.2%)with anaerobic bacteria,and 81 anaero-bic bacteria stains were isolated.The highest bacteria isolation rate of Gram positive anaerobic bacteria could be found in Peptostreptococcus,Bifidobacterium and Pemphigus propionibacterium.No cefoxitin, amoxicillin/carat acid resistant strain was detected in the above three Gram positive anaerobic bacteria. The highest bacteria isolation rate of Gram negative anaerobic bacteria could be detected in Porphy-romonas and Prevotella.No metronidazole,cefoxitin,amoxicillin/carat acid resistant strain was found in the two Gram negative anaerobic bacteria.In the study,48 patients with oral and maxillofacial infection were treated according to the results of drug resistance testing,and the clinical cure rate was 81 .3%. Conclusion:Mixed aerobic and anaerobic bacteria cultures are very common in most oral and maxillofa-cial infection patients.Anaerobic bacteria culture and drug resistance testing play an important role in clinical treatment.

Objective To investigate the expression levels of Ezrin and AnnexinⅡ in gallbladder carci-noma and their association with clinicopathologic parameters and metastasis potential. Methods The tissue mi-croarray consisted of 59 gallbladder carcinoma tissues and 6 normal gallbladder tissues were examined for the ex-pression of Ezrin and AnnexinⅡusing immunohistochemistry technique. The expression of Ezrin and AnnexinⅡin 20 cases of fresh gallbladder carcinoma and 6 cases of normal gallbladder were measured with western blot. Results The expression of Ezrin and AnnexinⅡ were higher in the gallbladder cancer than those in the normal gallbladder tissue. The positive rate of Ezrin and AnnexinⅡ were 47.5% and 50.8% respectively. The expression of Ezrin was significantly correlated with live metastasis , lymph node metastasis and Nevin stages. The expression of AnnexinⅡwas significantly correlated with live metastasis , differentiation levels and Nevin stages. The expres-sion of Ezrin was correlated with AnnexinⅡ. Results of western blot suggested that Ezrin and Annexin II were highly expressed in gallbladder carcinoma tissues. The high expression of Ezrin and Annexin is closely related with liver invasion. Conclusion Measurement of the expression of Annexin and Ezrin II have important clinical significances to evaluate the malignant biological behavior of gallbladder carcinoma.