USP21 contributes to the aggressiveness of laryngeal cancer cells by deubiquitinating and stabilizing AURKA.

Laryngeal cancer is a usual malignant tumor of the head and neck. The role and mechanism of deubiquitinase USP21 in laryngeal cancer are still unclear. We aimed to explore whether USP21 affected laryngeal cancer progress through deubiquitinating AURKA. USP21 and AURKA levels were evaluated by qRT-PCR and Western blot. Kaplan-Meier analysis was conducted by survival package. MTT was performed to detect cell proliferation. The wound healing assay was applied to evaluate cell migration. Transwell was used to measure cell invasion. Co-IP and GST-pull down determined the interaction between USP21 and AURKA. In addition, AURKA ubiquitination levels were analyzed. USP21 was signally elevated in laryngeal cancer tissues and cells. USP21 level in clinical stages III-IV was higher than that in clinical stages I-II, and high levels of USP21 were highly correlated with poor prognosis in laryngeal cancer. USP21 inhibition suppressed AMC-HN-8 and TU686 cell proliferation, migration and invasion. Co-IP and GST-pull down confirmed the interaction between USP21 and AURKA. Knockdown of USP21 markedly increased the ubiquitination level of AURKA, and USP21 restored AURKA activity through deubiquitination. In addition, overexpression of AURKA reversed the effects of USP21 knockdown on cell growth, migration, and invasion. USP21 stabilized AURKA through deubiquitination to promote laryngeal cancer progression.

Salt-like transcription factor 4 promotes laryngeal cancer progression through transcriptional activation of ubiquitin-specific protease 21 to stabilize Yin Yang 1.

Laryngeal cancer (LC) is a rare and challenging clinical problem. Our aim was to investigate the mechanism of salt-like transcription factor 4 (SALL4) in LC. LC tissue and paracancerous tissue were collected. Relative mRNA or protein levels were measured by quantitative real-time polymerase chain reaction or Western blot. MTT, wound healing, and transwell assay were performed to evaluate cell proliferation, migration and invasion. The binding relationship between SALL4 and USP21 promoter was verified by dual-luciferase assay and ChIP. Co-IP and glutathione-S-transferase (GST)-pull down were performed to measure the protein interaction between USP21 and YY1. Additionally, YY1 ubiquitination level was analyzed. It was found that SALL4 mRNA and SALL4 protein levels were elevated in LC clinical tissues and various LC cells. Knockdown of SALL4 inhibited epithelial-mesenchymal transition (EMT) of LC cells. USP21 was transcriptionally activated by SALL4. Co-IP and GST-pull down confirmed USP21 interacted with YY1. USP21 protected YY1 from degradation through deubiquitination. Furthermore, overexpression of USP21 reversed the effect of knockdown of SALL4 on YY1 and EMT in LC cells. In general, SALL4 facilitated EMT of LC cells through modulating USP21/YY1 axis.

Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain.

BACKGROUND: Duodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization. METHODS: A diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed. RESULTS: The results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain. CONCLUSION: These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.

Effect of neuromuscular electrical stimulation for fatigue management in patients with advanced laryngeal cancer receiving chemoradiotherapy.

This study retrospectively investigated the effect of neuromuscular electrical stimulation (NMES) for fatigue management in patients with advanced laryngeal cancer (ALC) receiving chemoradiotherapy.A total of 60 eligible patients with ALC receiving chemoradiotherapy were included. These patients were assigned equally to a treatment group and a control group. Patients in the treatment group received NMES therapy and were treated for a total of 8 weeks, while the patients in the control group did not receive NMES therapy. The primary outcome was fatigue, measured by the multidimensional fatigue inventory (MFI). The secondary outcomes included anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS), and sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI). All outcomes were evaluated before and after 8-week NMES treatmentAfter 8-week NMES treatment, the patients in the treatment group did not exert better effect than patients in the control group in fatigue relief, measured by the MFI score, anxiety and depression decrease, assessed by HADS, and sleep quality improvement, evaluated by PSQI.The results of this study demonstrate that NMES may not benefit for fatigue relief in patients with ALC receiving chemoradiotherapy. Future studies should still focus on this topic and warrant these results.

Quality of life in Chinese patients with laryngeal cancer after radiotherapy.

This retrospective study explored the quality of life (QoL) in Chinese patients with laryngeal cancer (LC) after radiotherapy.Fifty-nine eligible patients with Tis-T4 LC were included in this retrospective study. All patients received radiotherapy. Outcomes were measured by the core measure Questionnaire-C30 (QLQ-C30), and the disease-specific Head & Neck cancer module (QLQ-H&N35). All outcomes were assessed before and 3 months after the radiotherapy.Three months after the radiotherapy, all items of QLQ-C30 and QLQ-H&N35 scales changed significantly (P < .05), except the social functioning (P = .09), role activities (P = .81), and global (P = .12) in QLQ-C30 scale and social contacts (P = 1.00), teeth problems (P = .21), trismus (P = 1.00), and feeling ill (P = .07) in QLQ-H&N35 scale, compared with these items before the radiotherapy.The results of this study showed that most items of QoL changed significantly after 3 months of radiotherapy in Chinese patients with LC.

Effect of voice rehabilitation training on the patients with laryngeal cancer after radiotherapy.

This retrospective study examined the effect of voice rehabilitation training (VRT) for patients with laryngeal cancer (LC) after radiotherapy.Eighty-three eligible patients with LC were included. Forty-three patients were assigned to a treatment group, and underwent VRT, while the other 40 subjects were assigned to a control group, and were at waiting list. Primary outcome was measured by the Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale. Secondary outcome was measured by Patient Perception Measures. All outcomes were measured before and 3 months after VRT intervention.Patients in the treatment group did not show better outcomes, measured by GRBAS scale (Grade, P = .78; Roughness, P = .61; Breathiness, P = .83; Ashenia, P = .89; and Strain, P = .41), and Patient Perception Measures (Vocal quality, P = .17; Acceptability, P = .35; Hoarseness, P = .23; Vocal fatigue, P = .39; and Ashamed, P = .51), compared with patients in the control group.The results of this study did not exert better outcomes in patients received VRT than those at waiting list.

Chemopreventive effect of Myricetin, a natural occurring compound, on colonic chronic inflammation and inflammation-driven tumorigenesis in mice.

Myricetin is a flavonoids compound extracted from edible myrica rubra. We aimed to evaluate the efficacy of Myricetin on colonic chronic inflammation and inflammation-driven tumorigenesis in mice. Myricetin was administrated by gavage for 4 consecutive weeks. Mice were sacrificed and the number of colonic polyps was counted. Myricetin significantly inhibited AOM/DSS-induced colitis and colorectal tumorigenesis. Myricetin prevented the incidence of colorectal tumorigenesis and reduced the size of colorectal polyps. Histopathologic analysis showed that Myricetin could attenuate the degree of colonic inflammation and colorectal tumorigenesis. Further analysis showed that Myricetin strongly reduced the levels of inflammatory factors TNF-α, IL-1ß, IL-6, NF-κB, p-NF-κB, cyclooxygenase-2 (COX-2), PCNA and Cyclin D1 in the colonic tissues as analyzed by the assays of immunohistochemical staining, Western blotting and Q-RT-PCR. Our results demonstrated that Myricetin possesses the biological activities of chemoprevention colonic chronic inflammation and inflammation-driven tumorigenesis. We suggest that Myricetin could be developed as a promising chemopreventive drug for reducing the risk of colorectal cancer.

Gap junction -mediated cAMP movement between oocytes and somatic cells.

Cyclic AMP (cAMP) plays a critical role in oocyte meiotic maturation. However, the source of cAMP surge prior to maturation and the direction of gap junction-dependent cAMP movement are unclear. In this study, inhibition of gap junctional communication (GJC) using carbenoxolone (3.5 h) induced meiotic resumption in ~90% of follicle-enclosed oocytes (FEOs). The concentration of cAMP in a single oocyte was higher than that in a single cumulus cell, suggesting that the movement of cAMP proceeds from the oocyte to cumulus cells under passive diffusion. The mRNAs of adenylyl cyclases and the corresponding proteins were mainly detected in oocytes. Persistent or transient incubation with forskolin induced meiotic resumption in FEOs. The maturation induced by persistent forskolin treatment was inhibited by carbenoxolone. However, carbenoxolone had no effect on the maturation of FEOs transiently treated with forskolin or persistently treated with follicle-stimulating hormone. Oocyte maturation was inhibited by sequential treatment with carbenoxolone followed by forskolin. The carbenoxolone-induced maturation was accompanied by a cAMP surge, increased PDE3A and MAPK activation, and decreased levels of cGMP and cAMP-dependent PKA I activation.