Celastrol Reverses Palmitic Acid-Induced Insulin Resistance in HepG2 Cells via Restoring the miR-223 and GLUT4 Pathway.

OBJECTIVES: The natural triterpenoid compound celastrol ameliorates insulin resistance (IR) in animal models, but the underlying molecular mechanism is unclear. In this study, we investigated how celastrol regulates IR. METHODS: The HepG2 cellular IR model was initially established with palmitic acid (PA). The expression and activity of glucose transporter 4 (GLUT4), insulin receptor substrate-1 (IRS1) and 9 microRNAs (miRNAs) (miR-7, -34a, -96, -113, -126, -145, -150, -223 and -370) were detected before and after celastrol treatment using the PA-induced HepG2 IR model. RESULTS: The results showed that 250 µM PA for ≥2 days was optimal for inducing IR in HepG2 cells; 600 nM celastrol significantly attenuated the PA-induced IR in HepG2 cells. The PA-induced GLUT4 and IRS1 downregulation and Ser307 phosphorylation on IRS1 was reversed by subsequent treatment with 600 nM celastrol for 6 h. We next investigated which IR-related miRNAs were possible upstream regulators of celastrol-mediated reversal of PA-induced HepG2 IR. Two miRNAs, miR-150 and -223, were significantly downregulated by PA and were re-raised by subsequent celastrol treatment; and miR-223 was upstream of miR-150. Moreover, knocking down miR-223 abolished celastrol's anti-IR effects in the PA-induced model. CONCLUSIONS: Collectively, our results demonstrated that celastrol reverses PA-induced IR-related alterations, in part via miR-223 in HepG2 cells. Further investigation is warranted for establishing the clinical potential of celastrol in treating IR-related disorders.

Prevalence of human papillomavirus and Epstein-Barr virus DNA in Chinese children with tonsillar and/or adenoidal hypertrophy.

Tonsillar and adenoidal hypertrophy are prevalent otolaryngologic disorders in children, but their pathogenesis is largely unknown. The presence of human papillomavirus (HPV) and Epstein-Barr virus (EBV) DNA in 146 tonsil and/or adenoid tissue specimens from 104 Chinese children with tonsillar and/or adenoidal hypertrophy were screened using flow-through hybridization gene-chip technology and real-time fluorescence-based quantitative PCR. Then, the relationships between the prevalence of the viruses and other clinical characteristics of tonsillar and/or adenoidal hypertrophy were analyzed. No patient had HPV DNA. EBV DNA was detected in 19/42 (45.2%) tonsil tissues and 72/104 (69.2%) adenoid tissue specimens (P < 0.05). EBV DNA was not related to the patients' age, gender, disease course, or nationality, but children positive for EBV were less likely to snore; 14/15 (93.3%) patients who did not snore and 59/89 (66.3%) patients who snored were EBV positive. EBV DNA, but not HPV DNA was detected in Chinese children with tonsillar and/or adenoidal hypertrophy. Adenoid tissues might more susceptible than tonsil tissues to EBV infection. In addition, EBV infection did not aggravate snoring in patients with tonsillar and/or adenoidal hypertrophy.

Distribution of 37 human papillomavirus types in parotid gland tumor tissues.

Human papillomavirus (HPV) infection has been shown to be associated with human tumorigenesis. The aim of the present study was to demonstrate the association between HPV infection and parotid gland tumors. Paraffin-embedded tissue sections from 59 cases of parotid gland tumors and 20 normal oral mucosa were subjected to DNA extraction and flow-through hybridization and gene chip technology to detect infection of 37 HPV types. The HPV-positive rate was 57.6% in parotid gland tumor paraffin-embedded tissue specimens, whereas, the normal control group was negative for HPV. The HPV-positive rate was 59.6% in parotid gland benign tumor tissues and 42.9% in parotid malignant tissues. HPV infection in parotid gland tumors was dominated by the high-risk subtypes (80.7%), which mainly consisted of HPV 16, 18 and 52 (61.4%). In addition, parotid gland tumor tissues were found to be infected by multiple or single types of HPV, but were predominantly infected by mixed HPV types. In this study, we found that the occurrence of parotid gland tumor is correlated with HPV infection.

Human papillomavirus infection in nasal polyps in a Chinese population.

In order to determine the prevalence and genotype distribution of human papillomavirus (HPV) infection in patients with nasal polyps, a total of 204 patients with nasal polyps and 36 healthy controls were recruited for this study. Genomic DNA was extracted from paraffin-embedded tissue sections. HPV DNA genotyping was achieved by a flow-through hybridization and gene-chip method. HPV-positive infection was identified in 82 of 204 (40.2 %) patients, while HPV DNA was not found in healthy controls (P<0.05). Genotyping analysis showed that low-risk HPV genotype 11 was the most prevalent type of HPV in nasal polyps (45.28 %). Both single and multiple HPV genotype infections were found in these HPV-positive cases, although most (74.39 %) were infected with a single genotype. In addition, there was no correlation between HPV infection or HPV subtypes and the clinicopathological characteristics of patients, such as age, gender, number of surgery and disease course. The data from our study clearly demonstrated that HPV infection was associated with nasal polyps. Both high-risk HPV and low-risk HPV (LR-HPV) genotypes were identified in nasal polyp tissues, and LR-HPV-11 was the most prevalent type. Future research will explore the association of HPV infection with the development and progression of nasal polyps.