Caspase-3/gasdermin-E axis facilitates the progression of coronary artery calcification by inducing the release of high mobility group box protein 1.

Coronary artery calcification (CAC) is commonly observed in atherosclerotic plaques, which is a pathogenic factor for severe coronary artery disease (CAD). The phenotype changes of vascular smooth muscle cells (VSMCs) are found to participate in CAC progression, which is mainly induced by vascular inflammation and oxidative stress (OS). HMGB1, a critical inflammatory cytokine, is recently reported to induce arterial calcification, which is regulated by the Caspase-3/gasdermin-E (GSDME) axis. However, the function of the Caspase-3/GSDME axis in CAC is unknown. Herein, the involvement of the Caspase-3/GSDME axis in CAC was studied to explore the possible targets for CAC. CAC model was constructed in mice, which was verified by red cytoplasm in coronary artery tissues, increased macrophage infiltration, aggravated inflammation, and enhanced RAGE signaling, accompanied by an increased release of HMGB1 and an activated Caspase-3/ GSDME axis. In ß-GP-treated MOVAS-1 cells, calcification, the ROS accumulation, enhanced LDH and HMGB1 release, enlarged macrophage production, aggravated inflammation, and activated RAGE signaling were observed, which were markedly abolished by the transfection of si-HMGB1 and si-GSDME. Moreover, the calcification deposition, the activity of Caspase-3/ GSDME axis, release of HMGB1, macrophage infiltration, cytokine production, and RAGE signaling in CAC mice were notably alleviated by VSMCs-specific GSDME knockdown, not by hematopoietic stem cells (HSCs)-specific GSDME knockdown. Collectively, Caspase-3/GSDME axis facilitated the progression of CAC by inducing the release of HMGB1.

Simultaneous thyroglossal duct cyst with parathyroid cyst: A case report.

BACKGROUND: Thyroglossal duct cysts (TDC) are common congenital deformities. Most of them are cysts formed by the thyroglossal ducts that do not disappear and degenerate in the early embryonic stage. TDC exists alone and is rarely complicated by other congenital embryonic malformations. Only a few reports of TDC with branchial cleft cysts, thyroid cancer, thyroid hematoma, and epidermoid cysts have been reported. Therefore, we report a patient with TDC and parathyroid cyst (PC), a rare disease that has never been reported. CASE SUMMARY: A 47-year-old woman presented to clinic in April 2021 with a neck tumor which she had noticed 5 d earlier. We perfected the relevant examinations, such as ultrasound and computed tomography, and resected the tumor. After surgical treatment, the pathology revealed a cervical thyroglossal duct cyst and a left lobe parathyroid cyst. The patient was followed up for 1 year without significant recurrence. CONCLUSION: We report a patient with a simultaneous TDC and a PC to explore the correlation between the two congenital anomalies.

Submandibular solid-cystic mass as the first and sole manifestation of occult thyroid papillary carcinoma: A case report.

BACKGROUND: Occult thyroid papillary carcinoma (OTPC) is typically characterized by initial presentation with cervical lymph node metastasis and can be detected through ultrasound. However, the initial and sole manifestation was a submandibular solid-cystic mass. High-frequency ultrasound, enhanced multislice computed tomography (CT) scan, and thyroid function tests revealed no abnormalities, which is relatively uncommon. CASE SUMMARY: A 24-year-old Chinese female, who studied at a university in Shandong Province, presented to the clinic in June 2019 with a right submandibular mass that she had noticed 2 mo earlier. Clinical examination revealed a 2-cm, nontender, movable solid-cystic mass in the submandibular region, with no palpable thyroid mass observed. Ultrasonography revealed a 2.0 cm × 1.1 cm solid-cystic mass in the right submandibular region, and the thyroid gland showed no abnormalities. CT scan and 131I whole body follow-up scan showed that there were no abnormalities in the thyroid. However, cytology and pathology showed papillary tumor cell clusters, consistent with papillary thyroid carcinoma. Thus, we performed total thyroidectomy and right neck lymph node dissection. The pathology revealed the thyroid was detected as classical thyroid micropapillary carcinoma, and lymph nodes of levels VI central and levels II, III, IV, V on the right side showed no tumor metastasis. The patient was followed up for 2 years without significant recurrence. CONCLUSION: The presentation of a submandibular solid-cystic mass as the primary and solitary indication of OTPC is relatively uncommon. Fine needle aspiration is advised for evaluating neck masses.

MiR-145 inhibits the migration and invasion of papillary thyroid carcinoma cells through NF-κB pathway regulation.

Papillary thyroid carcinoma (PTC) is the most prevalent cancer in the endocrine system, and the number of patients diagnosed with PTC has been increasing rapidly in recent years. Previous studies have reported that miR-145 plays an important role in many kinds of cancers, but its function in PTC remains unclear. In this study, we found that compared to paracancerous tissues, the level of miR-145 expression was significantly downregulated in PTC tissues. When miR-145 is overexpressed, migration and invasion of PTC cells were suppressed in vitro. In addition, we found that miR-145 downregulated the nuclear factor-κB (NF-κB) pathway in PTC cells. Taken together, our data suggest that miR-145 functions as a tumor suppressor in PTC with the suppressive effect related to downregulation of the NF-κB pathway.

Inhibitory effects of miR­26b­5p on thyroid cancer.

In order to examine the inhibitory effects of microRNA (miR)­26b­5p on thyroid cancer (TC), the clinicopathological features and pathological tissues of 67 patients were collected. The expression levels of miR­26b­5p were detected in TC and paracarcinoma tissues by quantitative polymerase chain reaction, and the association between miR­26b­5p expression and the clinicopathological features of the patients was analyzed using t­test or one­way analysis of variance. In addition, B­CPAP TC cells were infected with a lentivirus to induce miR­26b­5p overexpression and proliferation was detected by Cell Counting kit­8. Subsequently, migration and invasion were detected by Transwell and Matrigel assays, respectively, and the molecular mechanism of action was investigated by western blotting. The results demonstrated that the expression levels of miR­26b­5p were significantly lower in TC tissues compared with paracarcinoma tissues (P<0.01), and miR­26b­5p was associated with lymph node metastasis (P<0.05). In addition, overexpression of miR­26b­5p inhibited the proliferation, invasion and migration of B­CPAP cells. Western blot analysis demonstrated that the protein expression levels of phosphorylated glycogen synthase kinase­3ß (pGsk­3ß) were decreased, and the expression of ß­catenin was decreased in B­CPAP cells overexpressing miR­26b­5p. These results demonstrated that miR­26b­5p may exert antitumor activity. In addition, at the molecular level, these effects may be associated with the Gsk­3ß/ß­catenin pathway.

MMP-11 promotes papillary thyroid cell proliferation and invasion via the NF-κB pathway.

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, and its incidence is on the rise. It has been reported that some matrix metalloproteinases (MMPs) are abnormally expressed in PTC and can be used as diagnostic markers. However, few studies have explored the underlying mechanisms by which MMPs promote tumor progression. In this study, we used microarray analysis to compare the variations of gene expression within the PTC cell populations and their adjacent normal tissues and found that MMP-11 was the most differentially expressed MMP. To investigate the role of MMP-11 in the mediation of thyroid cancer cell development, pEnter-MMP-11 plasmid, and MMP-11 small interfering RNA were applied to up- and downregulate MMP-11 expression of in cultured PTC cell lines K1 and BCPAP. The results suggested that the levels of proliferation and migration of cells transfected with MMP-11 siRNA were significantly reduced, while the levels in MMP-11-plasmid-transfected cells were increased. In terms of the mechanism, experimental data showed that the change in cyclin D1 is consistent with MMP-11 expression, which may explain the changes in proliferation. In addition, Western blot assay was conducted to analyze the p65 and activated (phospho-) p65 protein levels concomitant with MMP-11 adjustments. Variations in intracellular MMP-11 significantly altered the amount of phospho-p65 in thyroid cells, while p65 knockdown did not affect MMP-11 expression. These results suggest that MMP-11 is located upstream of p65 and regulates its activity. Interestingly, the data for the Transwell assay suggested that MMP-11 regulatory migration is also associated with the NF-κB p65 signaling pathway. In conclusion, this report describes the important role of MMP-11 in the regulation of thyroid cell proliferation and migration. Mechanistic studies have shown that cyclin D1 and p65 are important mediators in the processes, which provides a new way to study the mechanism of MMPs promoting the progression of thyroid cancer.