Anti-photoaging effects of canola meal extract on human dermal fibroblasts against UVB-induced oxidative stress.

Canola meal, a by-product of canola oil processing, is a source of bioactive compounds that show antioxidant and skin anti-aging effects through upcycling (i.e., creative reuse). Here we describe the antioxidant and skin anti-aging effects of canola meal extract (CME) obtained by upcycling canola meal. The antioxidant capacity of CME is due in part to its antioxidative phenolics. Seven phenolics, including sinapine and sinapic acid, in CME were identified using ultra-high-performance liquid chromatography-Orbitrap mass spectrometry. Addition of CME (1000 µg/mL) to human dermal fibroblast neonatal cells  significantly (p < 0.05) reduced matrix metalloproteinase-12 production and increased pro-collagen Ι alpha 1 content in response to ultraviolet B-induced oxidative stress compared with cells without CME. These results suggest that CME can serve as a functional food ingredient with antioxidant capacity and anti-aging effects on the skin.

Proliferation-Related Features of the Human Mesenchymal Stem Cells Derived from Palatine Tonsils, Adipose Tissues, and Bone Marrow.

BACKGROUND: Mesenchymal stem cells (MSCs) are widely used in regenerative medicine and cell-based transplantations. However, an in-depth comparison of the different MSC origins is lacking. This study aimed to compare the expression of adipose-derived (AMSCs), bone marrow-derived (BMSCs), and tonsil-derived (TMSCs) and evaluate whether TMSCs are good alternatives for AMSCs or BMSCs. METHODS: We analyzed the expression levels of 47,000 transcripts in AMSCs (n = 4), BMSCs (n = 4), and TMSCs (n = 4) using GeneChip. Microarray data were analyzed using the LIMMA package to compare the TMSCs, AMSCs, and BMSCs. Hub genes were analyzed using STRING and Cytoscape. To ascertain the functional roles of AURKA and AURKB, small interfering RNA (siRNA) molecules specifically targeting AURKA and AURKB mRNA were synthesized and employed to induce knockdown of AURKA and AURKB in TMSC and AMSC. We analyzed the expression level of OCT4, SOX-2, and NANOG genes in TMSC and AMSCs by cell culture and real-time PCR. RESULTS: We identified commonly increased 256 and decreased 160 genes in TMSCs from the differentially expressed genes (DEGs) between the TMSCs, AMSCs, and BMSCs. In the DEG-based protein-protein interaction and gene set enrichment analysis, hub genes (AURKA, AURKB, CDC20, and BUB1) highly expressed in TMSCs were enriched for development- and progression-related oocyte meiosis, the cell cycle, and ubiquitin-mediated proteolysis. In vitro analysis demonstrated that cells with downregulated expression of AURKA and AURKB exhibited a significant reduction in proliferation compared to control cells. However, silencing of the genes did not affect the differentiation capacity in TMSCs and AMSCs. CONCLUSION: Our study compared MSCs of different origins to better understand the similarities and differences among these cell types.

Effect of deferoxamine and ferrostatin-1 on salivary gland dysfunction in ovariectomized rats.

The mechanism underlying xerostomia after menopause has not yet been fully elucidated. This study aimed to investigate the mechanism of xerostomia and the effect of the ferroptosis inhibitors deferoxamine (DFO) and ferrostatin-1 (FER) on salivary gland dysfunction in a postmenopausal animal model. Twenty-four female Sprague-Dawley rats were randomly divided into four groups: a SHAM group (n = 6, sham-operated rats), an OVX group (n = 6, ovariectomized rats), an FER group (n = 6, ovariectomized rats injected intraperitoneally with FER), and a DFO group (n = 6, ovariectomized rats injected intraperitoneally with DFO). GPX4 activity, iron accumulation, lipid peroxidation, inflammation, fibrosis, and salivary gland function were analyzed. Recovery of GPX4 activity and a decrease in iron accumulation and cytosolic MDA + HAE were observed in the DFO group. In addition, collagen I, collagen III, TGF-ß, IL-6, TNF-α, and TGF-ß levels were decreased in the DFO group compared to the OVX group. Recovery of GPX4 activity and the morphology of mitochondria, and reduction of cytosolic MDA + HAE were also observed in the FER group. In addition, decreased expression of inflammatory cytokines and fibrosis markers and increased expression of AQP5 were observed in both the DFO and FER groups. Postmenopausal salivary gland dysfunction is associated with ferroptosis, and DFO and FER may reverse the postmenopausal salivary gland dysfunction after menopause. DFO and FER are hence considered promising treatments for postmenopausal xerostomia.

Effect of Echinochrome A on Submandibular Gland Dysfunction in Ovariectomized Rats.

Post-menopausal dry mouth or xerostomia is caused by reduced salivary secretion. This study aimed to investigate the efficacy of echinochrome A (Ech A) in alleviating submandibular gland dysfunctions in ovariectomized rats that mimic menopause. Female rats that were eight-weeks-old were randomly divided into SHAM-6, -12; OVX-6, -12; and ECH-6, -12 groups (consisting of 6- and 12-weeks post-sham-operated, ovariectomized, and Ech A-treated ovariectomized rats, respectively). The ECH groups had lower body weight than OVX but similar food intake and estradiol or estrogen receptor ß expression. However, the ECH groups had lower mRNA expression of sterol-regulatory element binding protein-1c (Srebp-1c), acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), cluster of differentiation 36 (Cd36), and lipid vacuole deposition than OVX mice. Moreover, reactive oxygen species (ROS), malondialdehyde (MDA), and iron accumulation were lower in the ECH than in the OVX groups. Fibrosis markers, transforming growth factor ß (Tgf-ßI and Tgf-ßII mRNA) increased in the OVX than SHAM groups but decreased in the ECH groups. Aquaporin (Aqp-1 and Aqp-5 mRNA) and mucin expressions were downregulated in the OVX groups but improved with Ech A. In addition, Ech A prevented post-menopausal salivary gland dysfunction by inhibiting lipogenesis and ferroptosis. These findings suggest Ech A as an effective remedy for treating menopausal dry mouth.

Tensin Regulates Fundamental Biological Processes by Interacting with Integrins of Tonsil-Derived Mesenchymal Stem Cells.

Human tonsil-derived mesenchymal stem cells (TMSCs) have a superior proliferation rate and differentiation potential compared to adipose-tissue-derived MSCs (AMSCs) or bone-marrow-derived MSCs (BMSCs). TMSCs exhibit a significantly higher expression of the tensin3 gene (TNS3) than AMSCs or BMSCs. TNS is involved in cell adhesion and migration by binding to integrin beta-1 (ITG ß1) in focal adhesion. Here, we investigated the roles of four TNS isoforms, including TNS3 and their relationship with integrin in various biological processes of TMSCs. Suppressing TNS1 and TNS3 significantly decreased the cell count. The knockdown of TNS1 and TNS3 increased the gene and protein expression levels of p16, p19, and p21. TNS1 and TNS3 also have a significant effect on cell migration. Transfecting with siRNA TNS3 significantly reduced Oct4, Nanog, and Sox-2 levels. Conversely, when TNS4 was silenced, Oct4 and Sox-2 levels significantly increase. TNS1 and TNS3 promote osteogenic and adipogenic differentiation, whereas TNS4 inhibits adipogenic differentiation of TMSCs. TNS3 is involved in the control of focal adhesions by regulating integrin. Thus, TNS enables TMSCs to possess a higher proliferative capacity and differentiation potential than other MSCs. Notably, TNS3 plays a vital role in TMSC biology by regulating ITGß1 activity.

ACE2 and TMPRSS2 Immunolocalization and COVID-19-Related Thyroid Disorder.

Thyroid dysfunction has been reported to be an extrapulmonary symptom of COVID-19. It is important to identify the tissue subset that expresses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are essential for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to understand the viral pathogenesis of COVID-19-related thyroid dysfunction. We investigated the expression and distribution of ACE2- and TMPRSS2-expressing cells in the thyroid gland. RT-PCR and Western blotting were performed on human thyroid follicular cells (Nthy-ori3-1) and rat thyroid tissues to detect the expression levels of ACE and TMPRSS2 mRNA and proteins. We also analyzed the expression patterns of ACE2 and TMPRSS2 in 9 Sprague-Dawley rats and 15 human thyroid tissues, including 5 normal, 5 with Hashimoto's thyroiditis, and 5 with Graves' disease, by immunohistochemistry (IHC) and immunofluorescence. Both ACE2 and TMPRSS2 mRNAs and proteins were detected in the thyroid tissue. However, ACE2 and TMPRSS2 proteins were not expressed in thyroid follicular cells. In IHC, ACE2 and TMPRSS2 were not stained in the follicular cells. No cells co-expressed ACE2 and TMPRSS2. ACE2 was expressed in pericytes between follicles, and TMPRSS2 was mainly stained in the colloid inside the follicle. There was no difference in expression between the normal thyroid, Hashimoto's thyroiditis, and Graves' disease. SARS-CoV-2 does not directly invade the thyroid follicular cells. Whether SARS-CoV-2 infection of pericytes can affect COVID-19-related thyroid dysfunction warrants further study.

Tonsil mesenchymal stem cells-derived extracellular vesicles prevent submandibular gland dysfunction in ovariectomized rats.

Dry mouth that occurs after menopause significantly reduces the quality of life of the elderly. The extracellular vesicles derived from mesenchymal stem cells are being studied for application in various pathological conditions in the field of tissue regenerative medicine. This study is to investigate the therapeutic effect on salivary gland dysfunction occurring after ovariectomy using tonsil mesenchymal stem cells (T-MSCs)-derived extracellular vesicles. The rats were divided into the following groups: sham-operated rats (SHAM), rats that underwent ovariectomy (OVX), and rats that underwent OVX surgery and were simultaneously injected with T-MSC-derived extracellular vesicles (OVX+EV). The rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in the OVX group compared with those in the SHAM group. Extracellular vesicles had no effect on estradiol levels or estrogen receptor ß expression. The evaluation of pro-inflammatory cytokines, TNF-α and IL-6, increased in the OVX group and decreased in the OVX+EV group. The expressions of collagen I and TGFßI increased in the OVX group but decreased in the OVX+EV group. Moreover, to examine submandibular gland function, AQP5 and α-amylase expressions were downregulated in the OVX group, but improved upon exosome injection. In conclusion, T-MSC-derived extracellular vesicles are useful for the prevented submandibular gland dysfunction that occurs after menopause.

ACE2 and TMPRSS2 immunolocalization and oral manifestations of COVID-19.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the host cells depends on the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). We investigated the distribution of ACE2- and TMPRSS2-expressing cells in various oral tissues to identify the underlying mechanism of oral manifestations in patients with coronavirus disease 2019. SUBJECTS: We analyzed the expression patterns of ACE2 and TMPRSS2 in the oral mucosa (tongue, palate, and buccal mucosa), trigeminal ganglion, vessels, and salivary glands of 9 Sprague-Dawley rats using immunohistochemistry and immunofluorescence. RESULTS: ACE2 and TMPRSS2 were strongly expressed in the intermediate layer of the squamous epithelia of tongue papillae and buccal mucosa. ACE2- and TMPRSS2-positive cells were observed in the taste buds of the tongue. Additionally, ACE2 and TMPRSS2 were co-expressed in the ductal epithelium and acinar cells of salivary glands. Furthermore, both ACE2 and TMPRSS2 were stained in the neuronal cell body of trigeminal ganglia, but not in Schwann cells. Moreover, ACE2 and TMPRSS2 were expressed in capillaries, but not in venules/arterioles. CONCLUSIONS: SARS-CoV-2 can spread the suprabasal area of squamous epithelia of the oral mucosa, invades taste bud, trigeminal nerve, parotid gland, and microvessel, resulting in oral manifestations.

The mechanism of submandibular gland dysfunction after menopause may be associated with the ferroptosis.

Salivary gland dysfunction is a common symptom that occurs after menopause. This study was performed to investigate the mechanism of salivary gland dysfunction to confirm the relationship between ferroptosis and salivary gland dysfunction by ovariectomy. Forty-eight female rats were randomly divided into four groups (12 rats in each group). Histology, real time PCR, western blot, immunohistochemistry, electron microscopy, cytosolic iron assay, and salivary function were analyzed. Human salivary gland tissue analysis was also done. Lipogenesis and lipid deposition in the submandibular gland tissue occurred after ovariectomy. ROS generation, MDA+HAE was increased and GPX4 activity was decreased and in the OVX group compared to the CON group. Iron deposition in the submandibular gland tissue was increased in the OVX group. Submandibular gland fibrosis was increased and saliva secretion was decreased in the OVX group. In human submandibular gland analysis, lipid and iron deposition was also increased in the postmenopause group. This is the first in vivo study in which salivary gland dysfunction is associated with the ferroptosis in postmenopausal animal model. Increased lipid and iron deposition in normal submandibular gland tissues of postmenopausal women can suggest that the salivary gland dysfunction after menopause may be associated with the ferroptosis.

Human Tonsil-Derived Mesenchymal Stromal Cells Maintain Proliferating and ROS-Regulatory Properties via Stanniocalcin-1.

Mesenchymal stromal cells (MSCs) from various sources exhibit different potential for stemness and therapeutic abilities. Recently, we reported a unique MSCs from human palatine tonsil (TMSCs) and their superior proliferation capacity compared to MSCs from other sources. However, unique characteristics of each MSC are not yet precisely elucidated. We investigated the role of stanniocalcin-1 (STC1), an anti-oxidative hormone, in the functions of TMSCs. We found that STC1 was highly expressed in TMSC compared with MSCs from bone marrow or adipose tissue. The proliferation, senescence and differentiation of TMSCs were assessed after the inhibition of STC1 expression. STC1 inhibition resulted in a significant decrease in the proliferation of TMSCs and did not affect the differentiation potential. To reveal the anti-oxidative ability of STC1 in TMSCs themselves or against other cell types, the generation of mitochondrial reactive oxygen species (ROS) in TMSC or ROS-mediated production of interleukin (IL)-1ß from macrophage-like cells were detected. Interestingly, the basal level of ROS generation in TMSCs was significantly elevated after STC1 inhibition. Moreover, down-regulation of STC1 impaired the inhibitory effect of TMSCs on IL-1ß production in macrophages. Taken together, these findings indicate that STC1 is highly expressed in TMSCs and plays a critical role in proliferating and ROS-regulatory abilities.

The Protective Effect of Echinochrome A on Extracellular Matrix of Vocal Folds in Ovariectomized Rats.

Here, we investigated the effects of sex hormones on extracellular matrix (ECM)-related gene expression in the vocal fold lamina propria of ovariectomized (after ovary removal) rats and verified whether echinochrome A (ECH) exerts any therapeutic effects on ECM reconstitution after estrogen deficiency in ovariectomized rats. Sprague-Dawley female rats (9 weeks old) were acclimatized for a week and randomly divided into three groups (n = 15 each group) as follows: group I (sham-operated rats, SHAM), group II (ovariectomized rats, OVX), group III (ovariectomized rats treated with ECH, OVX + ECH). Rats from the OVX + ECH group were intraperitoneally injected with ECH at 10 mg/kg thrice a week after surgery for 6 weeks. And rats were sacrificed 6 weeks after ovariectomy. Estradiol levels decreased in OVX group compared with the SHAM group. ECH treatment had no effect on the levels of estradiol and expression of estrogen receptor ß (ERß). The evaluation of ECM components showed no significant changes in elastin and hyaluronic acid levels between the different groups. Collagen I and III levels were lower in OVX group than in SHAM group but increased in OVX + ECH group. The mRNA levels of matrix metalloproteinase (MMP)-1, -2, -8, and -9 were significantly higher in the OVX group than in the SHAM group, but decreased in the OVX + ECH group. Thus, changes were observed in ECM-related genes in the OVX group upon estradiol deficiency that were ameliorated by ECH administration. Thus, the vocal fold is an estradiol-sensitive target organ and ECH may have protective effects on the ECM of vocal folds in ovariectomized rats.

Effect of sex hormones on extracellular matrix of lamina propria in rat vocal fold.

OBJECTIVES: The role of sex hormones for voice changes in men and women is presently unknown. To determine the effect of sex hormone on the vocal fold, changes of the extracellular matrix (ECM) in vocal fold lamina propria were assessed in orchiectomized (ORX) and ovariectomized (OVX) rats. METHODS: Male and female Sprague-Dawley rats were divided into sham-operated control male (CON-ORX), ORX, sham-operated female (CON-OVX), and OVX rats. Histological changes and expression of ECM-related genes in lamina propria of the vocal fold were evaluated at 4 and 12 weeks after surgery. RESULTS: Testosterone and estradiol levels decreased in the ORX and OVX groups, respectively. ORX groups did not have significant changes compared with CON-ORX groups. However, the expression of hyaluronic acid (HA) was decreased in the OVX group compared with the CON-OVX group. The expression of collagen I in OVX was lower than in the CON-OVX group. Collagen III levels were elevated at 4 weeks in the OVX group, but collagen III levels were diminished at 12 weeks in the OVX group. Expression of elastin in the ECM was less dense in the OVX group compared with controls. The expression MMP-1 and MMP-9 showed significantly increase in the OVX group compared to the CON-OVX group. CONCLUSION: No changes of the ECM-related genes in the vocal fold lamina propria were observed in ORX groups with reduced testosterone. However, changes of several ECM-related genes were observed in OVX groups with decreased estrogen. These results indicate that the vocal fold is an estrogen-sensitive target organ and that decreased estrogen, not testosterone, can affect the expression of several ECM-related molecules of vocal fold. LEVEL OF EVIDENCE: NA Laryngoscope, 130:732-740, 2020.

Clinically Node-Negative Parotid Gland Cancers: Prognostic Factors of Survival and Surgical Extent.

OBJECTIVE: Conservative parotidectomy is known to reduce morbidity, but has been rarely examined in patients with clinically node-negative (cN0) parotid cancers. We evaluated the clinicopathological variables influencing the outcomes of these patients and the efficacy of conservative parotidectomy. METHODS: We reviewed the clinical and pathological data of 256 patients with cN0 parotid carcinomas who underwent curative surgery at our institution. Of these, 110 and 146 underwent conservative and total parotidectomy, respectively, with 83 undergoing elective neck dissection and 135 receiving postoperative radiotherapy. Univariate and multivariate analyses of variables predicting recurrence-free survival (RFS) and overall survival (OS) were performed. Morbidity, survival, and recurrence rates were compared between the conservative and total parotidectomy groups. RESULTS: The 5-year RFS and OS rates in all patients were 85.7 and 91.4%, respectively. Multivariate analysis showed that advanced T classification, positive resection margin, and high-histologic grade were independent prognostic factors for both RFS and OS. Among the 201 patients with low- or intermediate-grade parotid cancers, those who underwent total parotidectomy had a greater chance of facial nerve paralysis than those who underwent conservative parotidectomy (p < 0.001). The 5-year RFS and OS after conservative parotidectomy (93.7 and 100%, respectively) were not worse than those after total parotidectomy (85.5 and 90.9%, respectively). CONCLUSION: Patients with cN0 parotid cancers may be stratified by histological grade and T classification. Conservative parotidectomy may be suitable for early T1-2 low- or intermediate-grade tumors if a resection margin is secured.

Increased calcium channel in the lamina propria of aging rat.

The alterations of the extracellular matrix (ECM) in lamina propria of the vocal folds are important changes that are associated with decreased vibrations and increased stiffness in aging vocal fold. The aim of this study was to investigate the differences in gene expression of lamina propria using next generation sequencing (NGS) in young and aging rats and to identify genes that affect aging-related ECM changes for developing novel therapeutic target molecule. Among the 40 genes suggested in the NGS analysis, voltage-gated calcium channels (VGCC) subunit alpha1 S (CACNA1S), VGCC auxiliary subunit beta 1 (CACNB1), and VGCC auxiliary subunit gamma 1 (CACNG1) were increased in the lamina propria of the old rats compared to the young rats. The synthesis of collagen I and III in hVFFs decreased after si-CACNA1S and verapamil treatment. The expression and activity of matrix metalloproteinases (MMP)-1 and -8 were increased in hVFFs after the treatment of verapamil. However, there was no change in the expression of MMP-2 and -9. These results suggest that some calcium channels may be related with the alteration of aging-related ECM in vocal folds. Calcium channel has promising potential as a novel therapeutic target for the remodeling ECM of aging lamina propria.

Tensin-3 Regulates Integrin-Mediated Proliferation and Differentiation of Tonsil-Derived Mesenchymal Stem Cells.

Human palatine tonsils are potential tissue source of multipotent mesenchymal stem cells (MSCs). The proliferation rate of palatine tonsil-derived MSCs (TMSCs) is far higher than that of bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs (ADSCs). In our previous study, we had found through DNA microarray analysis that tensin-3 (TNS3), a type of focal adhesion protein, was more highly expressed in TMSCs than in both BMSCs and ADSCs. Here, the role of TNS3 in TMSCs and its relationship with integrin were investigated. TNS3 expression was significantly elevated in TMSCs than in other cell types. Cell growth curves revealed a significant decrease in the proliferation and migration of TMSCs treated with siRNA for TNS3 (siTNS3). siTNS3 treatment upregulated p16 and p21 levels and downregulated SOX2 expression and focal adhesion kinase, protein kinase B, and c-Jun N-terminal kinase phosphorylation. siTNS3 transfection significantly reduced adipogenic differentiation of TMSCs and slightly decreased osteogenic and chondrogenic differentiation. Furthermore, TNS3 inhibition reduced active integrin beta-1 (ITGß1) expression, while total ITGß1 expression was not affected. Inhibition of ITGß1 expression in TMSCs by siRNA showed similar results observed in TNS3 inhibition. Thus, TNS3 may play an important role in TMSC proliferation and differentiation by regulating active ITGß1 expression.

Inferior Turbinate Swing Technique: A Novel Surgical Route to Approach Maxillary Sinus Area Pathology.

The inferior turbinate is an important structure for maintenance of adequate physiologic function within the nasal cavity. However, it hampers access to lesions involving maxillary sinus areas, including postoperative mucocele or benign tumor, and acts as an inferior limit to widening the natural ostium of a maxillary sinus. Here, we introduce a novel technique, interior turbinate swing, to facilitate entry to the inferior meatus or maxillary sinus while maintaining integrity of the inferior turbinate. In this technique, the anterior part of inferior turbinate is cut with sharp scissors, rotated posteriorly, and held in the nasopharynx. The inferior turbinate swing technique was employed in 38 subjects, and no patients exhibited recurrence of the causative disease without complication. Therefore, we may conclude that the inferior turbinate swing technique is a simple, effective, and safe treatment option for the management of postoperative mucocele, maxillary sinusitis with narrow inlet, or benign tumors.

Evaluation of decellularized xenogenic porcine auricular cartilage as a novel biocompatible filler.

Fillers are products that fill the space in soft tissues of the human body and actively used in the various medical fields. Unfortunately, most of the cost-effective commercially available fillers are synthetic and have limitations in terms of their biocompatibility. Here, we evaluated the possible application of decellularized xenogenic cartilage as a long-lasting material for soft tissue augmentation and compared it with two commercially available fillers Artesense (polymethylmethacrylate microspheres) and Radiesse (calcium hydroxyapatite [CaHa]). To do so, porcine auricular cartilage was harvested, followed by freezing and grinding of the tissue into flakes. Then, we used 1% Triton X-100 to decellularize the flakes. We then, respectively, injected 0.1 cc of each material (decellularized xenogenic cartilage, Radiesse, and Artesense) into the subcutaneous layer at three different sites per subject in 12 Sprague-Dawley rats, and evaluated the inflammatory cell infiltration and foreign body reactions of each. Our data indicate that the infiltration of giant cells in the injection area was significantly lower in the decellularized xenogenic cartilage injection group than that in the Radiesse and Artesense injection groups. Further, we observed some neutrophil infiltration in the xenogenic cartilage and Artesense injection groups at 1 month, but these levels were much lower at 3 months (comparable to the Radiesse injection group). Thus, decellularized xenogenic cartilage may have a distinct advantage in terms of biocompatibility compared with other commercial injectable long-lasting fillers, making it one of the most feasible, natural, and cost effective materials in the market. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2708-2715, 2018.

Survival Outcome of Intermediate-Grade Salivary Gland Carcinoma.

OBJECTIVE: Histological grade is the most important factor for defining treatment strategies and predicting prognosis for salivary gland carcinoma (SGC). We examined factors affecting long-term recurrence and survival among intermediate-grade SGC (IGSGC) patients to define optimal treatment modalities and outcomes. METHODS: We reviewed the clinical and pathological data on 108 IGSGC patients who underwent definitive surgery with or without postoperative radiotherapy. We compared treatment outcomes by treatment strategies such as surgical extent for the primary tumor, neck dissection, or postoperative radiotherapy. RESULTS: During a 103-month median follow-up, local, regional, and distant recurrences were detected in 14 (13.0%), 3 (2.8%), and 21 (19.4%) patients, respectively. The 10-year locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 83.1, 76.0, and 80.1%, respectively. Multivariate analyses identified a nonparotid primary site as an independent prognostic factor for LRC (p = 0.018). Adenoid cystic carcinoma and a positive pN classification were significantly unfavorable prognostic factors for DMFS (p = 0.025 and p = 0.030, respectively); overall advanced stage was an independent prognostic factor for OS (p = 0.020). Surgical extent, elective neck dissection, and postoperative adjuvant radiotherapy did not significantly affect treatment outcomes. CONCLUSION: Patients with early-stage IGSGC of parotid origin can achieve favorable treatment outcomes with conservative surgery alone.

TSH-independent release of thyroid hormones through cold exposure in aging rats.

Thyroid function decreases and cold exposure response becomes impaired with increasing age. We investigated the age-related changes in thyroid structure and function and cold-induced changes in the thyroid activity of aging rats. Thirty-two male Sprague-Dawley rats were randomly divided into four groups (8 rats per group): young (7 months) and old (22 months) groups exposed to room temperature and cold stress. The active follicle ratio and serum free T3, T4 and TSH, and TSH receptor (TSHR) concentrations in the thyroid tissues of the rats from each group were compared. At room temperature, old rats had significantly lower active follicle ratio and free T3 and T4 concentrations than young rats. Furthermore, old rats displayed higher TSH level than young. Exposure to cold temperature led to significantly increased active colloid ratio and free T3 and T4 concentrations among old rats, but no significant differences were found among young rats. Additionally, no significant changes in the TSH and TSHR levels were observed after cold exposure in both young and old rats. Old rats have lower thyroid function than young rats under normal temperature. Aging rats are more susceptible to cold stress than young rats, and cold-induced thyroid activation occurs independently of TSH. We investigated the age-related changes in the thyroid structure and function and cold-induced changes in the thyroid activity of aging rats. Aging rats have structurally less active thyroid follicles and functionally lower thyroid hormone levels than young rats. Furthermore, old rats are more susceptible to cold stress than young rats, and cold-induced thyroid activation occurs independently of TSH.

Occult lymph node metastasis and risk of regional recurrence in papillary thyroid cancer after bilateral prophylactic central neck dissection: A multi-institutional study.

BACKGROUND: The impact of occult lymph node metastasis on regional recurrence after prophylactic central neck dissection for preoperative, nodal-negative papillary thyroid cancer is controversial. We investigated risk factors for regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection. Analysis was according to clinicopathologic characteristics and occult lymph node metastasis patterns. METHODS: This multicenter study enrolled 211 consecutive patients who underwent total thyroidectomy with bilateral prophylactic central neck dissection for papillary thyroid cancer without evidence of central lymph node metastasis on preoperative imaging. Clinicopathologic features and central lymph node metastasis patterns were analyzed for predicting regional recurrence. Multivariate Cox regression analysis was used to identify independent factors for recurrence. RESULTS: Median follow-up time was 43 months (24-95 months). Ten patients (4.7%) showed regional lymph node recurrence. The estimated 5-year, regional recurrence-free survival was 95.2%. Tumor size ≥1 cm, central lymph node metastasis, lymph node ratio, and prelaryngeal lymph node metastasis were associated with regional recurrence in univariate analysis (P < .05). In multivariate analysis, a lymph node ratio ≥ 0.26 was a significant risk factor for regional lymph node recurrence (odds ratio = 11.63, P = .003). Lymph node ratio ≥ 0.26 was an independent predictor of worse recurrence-free survival on Cox regression analysis (hazard ratio = 11.49, P = .002). CONCLUSION: Although no significant association was observed between the presence of occult lymph node metastasis and regional recurrence, lymph node ratio ≥ 0.26 was an independent predictor of regional lymph node recurrence in papillary thyroid cancer patients who underwent total thyroidectomy and bilateral prophylactic central neck dissection.