M2 Macrophages-Derived Exosomal miRNA-23a-3p Promotes the Progression of Oral Squamous Cell Carcinoma by Targeting PTEN.

Exosomes from tumor cells and immune cells regulate the tumor microenvironment through the biomolecules or microRNAs (miRNAs) they carry. This research aims to investigate the role of miRNA in exosomes derived from tumor-associated macrophages (TAMs) in the progression of oral squamous cell carcinoma (OSCC). RT-qPCR and Western blotting assays were used to determine the expression of genes and proteins in OSCC cells. CCK-8, Scratch assay and invasion-related proteins were utilized to detect the malignant progression of tumor cells. High-throughput sequencing predicted differentially expressed miRNAs in exosomes secreted by M0 and M2 macrophages. Compared with exosomes from M0 macrophages, exosomes from M2 macrophages led to enhanced proliferation and invasion of OSCC cells and inhibited their apoptosis. High-throughput sequencing results show that miR-23a-3p is differentially expressed in exosomes from M0 and M2 macrophages. MiRNA target gene database predicts that phosphatase and tensin homolog (PTEN) are target genes of miR-23a-3p. Further studies revealed that transfection of miR-23a-3p mimics inhibited PTEN expression in vivo and in vitro and promoted the malignant progression of OSCC cells, which was reversed by miR-23a-3p inhibitors. MiR-23a-3p in exosomes derived from M2 macrophages promotes malignant progression of OSCC. PTEN is a potential intracellular target of miR-23a-3p. MiR-23a-3p, an M2 macrophage-associated exosome, is a promising target for the future treatment of OSCC.

Moderate sedation by total intravenous remimazolam-alfentanil vs. propofol-alfentanil for third molar extraction: A prospective randomized controlled trial.

Background: Oral dental treatment cause anxiety, fear, and physical stress. This study aimed to investigate the efficacy and safety of moderate sedation by remimazolam with alfentanil vs. propofol with alfentanil in third molar extraction. Methods: This single-center, randomized, single-blind clinical trial included 100 adults who underwent third molar ambulatory extraction. All patients had continuous infusion of Alfentanil 0.2 µg/kg/min. Group remimazolam with alfentanil (group RA) had an induction dose of 80 µg/kg and maintenance dosage of 5 µg/kg/min. In group propofol with alfentanil (PA group), propofol was infused at an initial concentration of 1.8 µg/mL under target controlled infusion (TCI) mode and a maintenance concentration of 1.5 µg/mL. The incidence rates of adverse effects were recorded and compared. Depth of sedation was assessed using the modified observer alertness/sedation assessment (MOAA/S) and entropy index. Recovery characteristics were recorded and complications observed for next 24 h. Results: The incident of adverse events 6 (12%) in the group RA was lower than the group PA 25 (50%) [Mean difference 0.136 (95%CI, 0.049-0.377); P < 0.05], with no serious adverse events during the sedation procedure. The incidence of injection pain in group RA was significantly lower than that in group PA [4 vs. 26%, mean difference 0.119 (95%CI, 0.025-0.558); P = 0.004]. Before starting local anesthesia, the mean arterial pressure, heart rate, and respiratory rate of the PA group were lower than those of the RA group. None of the patients required further treatments for a decreased heart rate, blood pressure, or low SpO2. The rate of moderate sedation success was 100% in both groups. The MOAA/S score was similar between the groups indicating that the depth of sedation was effective. Group RA had significantly shorter recovery and discharge times than those of group PA. Conclusions: Remimazolam with alfentanil is a safer and more effective alternative for ambulatory sedation and can reduce recovery and discharge time and the incidence of perioperative adverse events compare with propofol. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier: ChiCTR2200058106.

The RNA-binding protein Musashi2 governs osteoblast-adipocyte lineage commitment by suppressing PPARγ signaling.

Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells (BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2 (Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling. RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.

A Case of a Persistent Postoperative Infection Caused by Multidrug-Resistant Kluyvera ascorbata in the Oral and Maxillofacial Region.

INTRODUCTION: Kluyvera ascorbata infection is rare, but it has been extensively studied because of its potential to cause a wide range of infections and its ability to transfer the gene encoding for CTX-M-type extended spectrum ß-lactamases (ESBLs) to other Enterobacteriaceae. CASE PRESENTATION: The authors report a case of a 61-year-old Chinese male with a persistent postoperative infection caused by a multidrug-resistant ESBL-producing K. ascorbata. Following antimicrobial susceptibility testing, he was aggressively treated with gentamicin and levofloxacin with a favorable outcome. CONCLUSION: To our knowledge, this is the first case report of a persistent postoperative infection caused by a multidrug-resistant K. ascorbata in the oral and maxillofacial region. The authors suggest that K. ascorbata infection warrants prompt identification and aggressive antibiotic management, given that ESBL-producing K. ascorbata is resistant to penicillins and first-generation to third-generation cephalosporins.

Expression of CLIC1 as a potential biomarker for oral squamous cell carcinoma: a preliminary study.

PURPOSE: CLIC1, a member of the highly conserved class ion-channel protein family, is frequently upregulated in multiple human malignancies and has been demonstrated to play a critical role in cell proliferation, apoptosis, and invasion. However, limited is known about its expression, biological functions, and action mechanism in oral malignancies. We aimed to evaluate whether CLIC1 could be a biomarker for oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemistry was used to analyze the expression of CLIC1 in tissue. CLIC1 protein and mRNA were measured through Western immunoblotting and quantitative real-time PCR. CLIC1 protein expression in plasma was detected via ELISA. A total of 72 OSCC specimens were recruited in this study for evaluation of correlations of CLIC1 with clinicopathological features and survival. RESULTS: CLIC1 was significantly overexpressed in tissue and plasma of OSCC patients. It was found that upregulated CLIC1 was distinctly correlated with histological grade, TNM stage, and tumor size. Meanwhile, Kaplan-Meier survival analysis showed that OSCC patients with high CLIC1 expression had remarkably poorer overall survival rate than those with low CLIC1 expression. Multivariate Cox regression analysis revealed that CLIC1 was the independent prognostic factor for overall survival rate of OSCC patients. In addition, Pearson correlation analysis showed that CLIC1 was associated with multiple tumor-associated genes. CONCLUSION: These results indicated that CLIC1 acts as a molecular target in OSCC and may present a novel diagnostic marker and therapeutic target for OSCC.

Osteopontin is Critical for Hyperactive mTOR-Induced Tumorigenesis in Oral Squamous Cell Carcinoma.

Mechanistic target of rapamycin (mTOR) plays a critical role in the development of oral squamous cell carcinoma (OSCC), but the underlying mechanisms remain poorly understood. Here we have demonstrated that the expression of osteopontin (OPN) was dramatically up-regulated in OSCC tissues and cell lines. Moreover, reduction of OPN suppressed cell proliferation, colony formation, and in vivo tumorigenic ability of OSCC cell lines Tca8113. In addition, there was a strong positive correlation between mTORC1 activity and OPN expression in OSCC tissues and cell lines. Furthermore, mTOR complex 1 (mTORC1) enhanced OPN expression through up-regulation of ERRα. Therefore, OPN is a downstream target of mTORC1 and is crucial for OSCC development. mTORC1, ERRα, and OPN may be potential targets for treatment of OSCC with aberrant mTORC1 signaling.

[Influence of different surgeries on growth and development of alar cartilage in young-rabbit].

OBJECTIVE: The purpose of this study is to observe the affection of different clinical surgeries on alar nasal cartilages' growth and development. The experimental results can provide some theory basis for clinical surgeries. METHOD: Twenty-eight New Zealand immature rabbits were used in this study, and divided into normal control group, hidden dissection group and cutting off alar nasal cartilages group randomly, which included 4,12 and 12 rabbits, separately. Arc incision were made on the mucous membrane of nasal cavity,and then dissect the alar nasal cartilages hidden or cut off the alar nasal cartilages, separately. The growth and development of the alar cartilage were observed at different stages after the surgery using histological and immuno-histochemical methods. RESULT: Four weeks, eight weeks, twelve weeks and sixteen weeks after surgery, there were no significant differences in the indexes of chondrocytes between hidden dissection group and control group. In cutting off alar nasal cartilages group, fiber tissue were observed in the vacancy left after being cut off cartilages, and even mucous membrane tissue could be seen in some slices. CONCLUSION: There is no adverse influence on the growth and development of the alar cartilage after being hidden dissected. Contrarily, the restoring capability of transparent cartilage cannot counteract the injury resulted form the surgery after the alar nasal cartilages being cut off.