Lymphoepithelial carcinoma of the submandibular gland is an extremely rare condition; therefore, no clear clinical features or established treatment is available for this. A 58-year-old Japanese man who came to our hospital with the complaint of swelling of the left submandibular region was diagnosed with stage IVa, T4aN2bM0 lymphoepithelial carcinoma of the submandibular gland. We also examined the relationship between the tumor and Epstein-Barr virus by Epstein-Barr virus encoded ribonucleoprotein in situ hybridization. The patient was treated by performing segmental mandibulectomy, neck dissection, mandibular reconstruction, and adjuvant chemoradiotherapy. After 2 years of treatment, good progress has been observed in the patient without any signs of recurrence. Here, we have reported the treatment of a patient with lymphoepithelial carcinoma of the submandibular gland using literature review.

OBJECTIVE: Sox2 plays crucial roles in tissues homeostasis and regeneration. However, there are lack of a comprehensive examination of Sox2 expression and its functional role in submandibular gland regeneration. Therefore, we aimed to elucidate the impact of Sox2 on submandibular gland regeneration.
METHODS: A Sprague-Dawley rat submandibular gland duct ligation/de-ligation regeneration model was conducted in this study. Sox2-shRNA vectors were retro-ductally administered into the submandibular gland to establish a stable Sox2 knockdown model. Conventional histopathological and molecular biological methods were used to investigate phenotypic changes.
RESULTS: The submandibular gland normalized completely 28 days after ligature removal (following 7 days of duct ligation). AQP5 expression gradually increased after ligation removal until returning to normal levels. In submandibular gland regeneration, Sox2 re-expressed and co-expressed with AQP5+ acinar cells, and Sox2 expression peaked on day 14, recovered to normal on day 28, reproducing the developmental pattern. Sox2 knockdown hindered gland regeneration and induced irreversible fibrosis. The AQP5 expression was significantly lower than the contemporaneous solely ligated group, while the blue collagen deposition and the Vimentin expression increased prominently. The expression of CD68, IL-1β, TNF-α and IL-17A increased significantly, and epithelial cells in the Sox2 knockdown group expressed higher levels of IL-17A.
CONCLUSIONS: These findings highlight Sox2 as a crucial regulator of the acinar cell lineage. Sox2+ progenitor cells are pivotal for acinar cell maintenance, which is indispensable for submandibular gland regeneration. Collectively, our findings may help develop targeted interventions for enhancing tissue repair and preventing irreversible fibrosis in salivary gland disorders.

Objective:To investigate the clinical effect of retroauricular hairline approach in submandibular gland resection assisted by endoscope. Methods:A total of 18 patients with submandibular gland benign tumors treated in our hospital from September 2022 to September 2023 were selected. A 5 cm incision was designed in the retroauricular hairline, and the flap was turned over directly to the anterior edge of sternocleidomastoid muscle, then the flap was turned over to build the cavity through endoscopic surgery, and submandibular gland resection was completed with the assistance of endoscope. After operation, a negative pressure drainage was placed into the hairline, and the wound was closed by continuous intracutaneous suture. The clinical effect was evaluated after 3-6 months follow-up. Results:All patients underwent submandibular gland resection with endoscopic assistance as planned, and none of them converted to submaxillary incision during operation. The operation time was 65-97 min, with an average of 75 min. Intraoperative bleeding was 10-20 mL, with an average of 14 mL.No tongue numbness, wound infection, or tumor recurrence occurred after operation. However, there were 10 patients with ear numbness and discomfort of auricle after surgery, which gradually recovered after 6-9 months of follow-up. Two patients had crooked mouth after surgery, and the symptoms were gradually relieved after follow-up. All incisions healed in stage I and were concealed. Conclusion:Endoscopic retroauricular hairline approach is a choice for submandibular gland resection with good cosmetic effect, less trauma and fewer complications.
目的：探讨腔镜辅助下经耳后发际内入路在颌下腺切除术的临床效果。 方法：选择2022年9月至2023年9月治疗的颌下腺良性肿瘤患者18例，在耳后发际内设计长约5 cm切口，先直视下翻瓣至胸锁乳突肌前缘附近，通过腔镜翻瓣建腔，在腔镜辅助下完成颌下腺切除术。术后经发际内放置负压引流，皮内连续缝合关闭创口。术后随访3～6个月，评价其临床效果。 结果：所有患者均按计划经腔镜辅助下完成颌下腺切除术，术中无一例中转为颌下切口。手术时间65～97 min，平均75 min；术中出血10～20 mL，平均14 mL；术后无舌体麻木、创口感染、肿瘤复发等情况出现，但有10例患者术后出现耳廓麻木不适，经随访6～9个月逐渐恢复；2例患者术后发生口角歪斜，经随访后症状逐渐缓解；切口均Ⅰ期愈合，且部位隐蔽。 结论：腔镜辅助经耳后发际内入路在颌下腺切除术的美容效果好、创伤小、并发症少，是颌下腺切除的一种手术入路选择。.

Intermittent fasting exerts a profound beneficial influence on a spectrum of diseases through various mechanisms including regulation of immune responses, elimination of senescent- and pathogenic cells and improvement of stem cell-based tissue regeneration in a disease- and tissue-dependent manner. Our previous study demonstrated that alternate-day fasting (ADF) led to alleviation of xerostomia and sialadenitis in non-obese diabetic (NOD) mice, a well-defined model of Sjögren\'s syndrome (SS). This present study delved into the previously unexplored impacts of ADF in this disease setting and revealed that ADF increases the proportion of salivary gland stem cells (SGSCs), defined as the EpCAMhi cell population among the lineage marker negative submandibular gland (SMG) cells. Furthermore, ADF downregulated the expression of p16INK4a, a cellular senescence marker, which was concomitant with increased apoptosis and decreased expression and activity of NLRP3 inflammasomes in the SMGs, particularly in the SGSC-residing ductal compartments. RNA-sequencing analysis of purified SGSCs from NOD mice revealed that the significantly downregulated genes by ADF were mainly associated with sugar metabolism, amino acid biosynthetic process and MAPK signaling pathway, whereas the significantly upregulated genes related to fatty acid metabolic processes, among others. Collectively, these findings indicate that ADF increases the SGSC proportion, accompanied by a modulation of the SGSC property and a switch from sugar- to fatty acid-based metabolism. These findings lay the foundation for further investigation into the functionality of SGSCs influenced by ADF and shed light on the cellular and molecular mechanisms by which ADF exerts beneficial actions on salivary gland restoration in SS.

Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice (n = 5 per group), a xerostomia animal model for Sjögren\'s syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs.

Intranodal palisaded myofibroblastoma (IPM) is a rare benign tumor of the lymph nodes, particularly in inguinal lymph nodes. IPM originating from the submandibular gland lymph nodes is rarely encountered in clinical practice. Herein, we report the case of a 31-year-old male patient with IPM of the submandibular gland region and describe in detail magnetic resonance imaging findings and pathology. Magnetic resonance imaging detected a heterogeneous lesion with a hypointense rim on T2-weighted imaging with specificity in the left submandibular gland region. This case report will contribute to the accumulation of experience in the diagnosis of this disease.

Cadmium (Cd), an element categorized as a non-essential transitional metal, has potential hazards to the health of both human beings and animals. Spirulina platensis (SP), a type of blue-green algae, possesses a high concentration of essential antioxidants. The present study aimed to explore the possible defensive role of SP against Cd-induced submandibular gland injury in rats by assessment of biomarkers related to both oxidative stress and inflammatory processes, which were further explored through histopathological examination of submandibular gland tissue. Consequently, the study included 32 mature rats, subdivided into four different groups as follows: control, SP, Cadmium chloride (CdCl2), and CdCl2/SP. The duration of the study was 24days. The results revealed that CdCl2 induced submandibular gland injury as shown by the oxidant/antioxidant imbalance and increased inflammatory reactions, in addition to, histopathological changes and overexpression of BAX immunostaining. Concurrent SP administration to CdCl2-treated rats significantly improved all these effects. We concluded that concurrent SP supplement improved the submandibular gland injury provoked by CdCl2.

OBJECTIVE: The aim of the present study is to show how sodium nitrite alters the histology of submandibular salivary glands and livers of Albino rats, as well as how chlorogenic acid may have therapeutic benefits.
METHODS: A sample size of thirty male Sprague Dawley Albino rats weighing between 100 and 150 g (5-6 weeks old) was randomly allocated into 3 equal groups. Group I: rats were used as controls and were given phosphate buffer solution, whereas Group II: rats were given an 80 mg/kg sodium nitrites (SN) daily dissolved in distilled water. The rats in Group III were given a daily dose of 80 mg/kg SN dissolved in distilled water and after 6 hours each rat received 50 mg/mL freshly prepared chlorogenic acid (CGA) every other day. For 12 weeks, all treatment modalities will be administered orally, every day. After the experiment, all rats were euthanized. Samples from salivary glands and livers were processed and stained with H&E and interleukin 6 (IL 6). Malondialdehyde (MDA) and superoxide dismutase (SOD) enzymes were detected using an ELISA assay.
RESULTS: Groups III had nearly comparable findings to Group I regarding histological pattern with normal submandibular glands and livers features. Group III salivary gland treated with CGA exhibited higher SOD levels (20.60±4.81 U/g) in comparison to the SN group, and lower MDA levels (111.58±28.28 nmol/mg) in comparison to the SN treated samples. In comparison to the SN group, CGA treatment significantly reduced MDA levels in liver samples (167.56±21.17 nmol/mg) and raised SOD (30.85±6.77 U/g).
CONCLUSIONS: Chlorogenic acid has a protective effect against salivary gland and liver toxicity induced by SN in rats. This was mediated via the anti-inflammatory and antioxidative properties of CGA and the restoration of oxidant/antioxidant balance in rat salivary gland and liver.

Diabetes mellitus (DM) is a chronic disorder of glucose metabolism that threatens several organs, including the submandibular (SMG) salivary glands. Antox (ANX) is a strong multivitamin with significant antioxidant benefits. The goal of this study was to demonstrate the beneficial roles of ANX supplementation in combination with insulin in alleviating diabetic SMG changes. For four weeks, 30 rats were divided into equal five groups (n = 6): (1) control group; (2) diabetic group (DM), with DM induced by streptozotocin (STZ) injection (50 mg/kg i.p.); (3) DM + ANX group: ANX was administrated (10 mg/kg/day/once daily/orally); (4) DM + insulin group: insulin was administrated 1U once/day/s.c.; and (5) DM + insulin + ANX group: co-administrated insulin. The addition of ANX to insulin in diabetic rats alleviated hyposalivation and histopathological alterations associated with diabetic rats. Remarkably, combined ANX and insulin exerted significant antioxidant effects, suppressing inflammatory and apoptotic pathways associated with increased salivary advanced glycation end-product (AGE) production and receptor for advanced glycation end-product expression (RAGE) activation in diabetic SMG tissues. Combined ANX and insulin administration in diabetic rats was more effective in alleviating SMG changes (functions and structures) than administration of insulin alone, exerting suppressive effects on AGE production and frustrating RAGE downstream pathways.

BACKGROUND: Canonical transient receptor potential channels play a crucial role in cancer cell proliferation. While TRPC6 subtype detection in submandibular glands and the relevance of some TRPC channels in this gland have been shown in animal models, its histological detection in human lacrimal and submandibular glands, as well as related tumors, lacks systematic study. Studying TRPC6 in humans could lead to new therapeutic options. This research aimed to immunohistochemically detect TRPC6 in human samples of physiological lacrimal and submandibular glands and of adenoid cystic carcinoma and mucoepidermoid carcinoma.
METHODS: Seven fixed body donors and samples of six cancer patients were examined. The ten tissue samples collected from the submandibular and lacrimal glands were then processed into histological slides and stained with hematoxylin-eosin. Tumor samples were provided as sections. TRPC6 presence was determined by immunohistochemistry, which was performed by indirect detection with a primary TRPC6 antibody, a secondary HRP-conjugated antibody and the chromogen diaminobenzidine.
RESULTS: Results confirm TRPC6 expression in all ten physiological gland samples: all samples showed a immunohistochemical signal with varying intensity. No significant gender-specific differences could be observed. TRPC6 was detected in four of six submandibular adenoid cystic carcinoma and the mucoepidermoid carcinoma samples, especially in tumor cells\' cytoplasma and nuclei. Excretory ducts consistently showed TRPC6. Mucous tubules, their nuclei and the nuclei of adipocytes generally showed no signal while serous acini and their nuclei showed a weak TRPC6 signal.
CONCLUSIONS: The discovery of TRPC6 in glandular tissue indicates a role in salivary gland function and calcium homeostasis is a basis for further research into its significance for tumor development in adenoid cystic carcinoma and mucoepidermoid carcinoma of salivary glands. TRPC6 could be used as a target for treatment of these tumors. However, the correlation between TRPC6 and submandibular and lacrimal gland diseases requires further exploration.