High expression of HHLA2 predicts poor prognosis in medullary thyroid carcinoma.

BACKGROUND: Human endogenous retrovirus-H long terminal repeat-associating protein 2 is a newly identified immune checkpoint molecule that was aberrantly expressed in many malignant tumors. However, its expression in medullary thyroid carcinoma is still unclear. This study aimed to investigate the human endogenous retrovirus-H long terminal repeat-associating protein 2 expression in medullary thyroid carcinoma tissues and to evaluate the relationships between its expression and clinicopathologic together with prognostic relevance. METHODS: Using 51 surgical specimens obtained from medullary thyroid carcinoma patients, the expression levels of the human endogenous retrovirus-H long terminal repeat-associating protein 2 protein in medullary thyroid carcinoma tumor tissues and adjacent noncancerous tissues were measured by immunohistochemistry, and its correlations with clinicopathologic and prognostic features were analyzed. Status of CD8+ tumor infiltrating lymphocytes was also investigated. RESULTS: The results showed that human endogenous retrovirus-H long terminal repeat-associating protein 2 was only detected in tumor tissues, and 31.4% of the medullary thyroid carcinoma patients had high expression of human endogenous retrovirus-H long terminal repeat-associating protein 2. High human endogenous retrovirus-H long terminal repeat-associating protein 2 expression was significantly associated with lymph node metastasis and advanced American Joint Committee on Cancer stages (P = 0.005). There existed an inverse trend between human endogenous retrovirus-H long terminal repeat-associating protein 2 expression and CD8+ tumor infiltrating lymphocytes infiltration in medullary thyroid carcinoma tumor samples (P = 0.042). The log-rank test showed a shorter disease-free survival in patients with high human endogenous retrovirus-H long terminal repeat-associating protein 2 expression (P = 0.002). The disease-free survival rates were also significantly low in cases of medullary thyroid carcinoma with lymph node metastasis, American Joint Committee on Cancer stages III-IV and multifocality. Multivariate Cox analysis confirmed that human endogenous retrovirus-H long terminal repeat-associating protein 2 acted as an independent predictive factor in the disease-free survival of medullary thyroid carcinoma patients (hazard ratio = 4.138, 95% confidence interval: 1.027-16.667, P = 0.046). CONCLUSIONS: Taken together, human endogenous retrovirus-H long terminal repeat-associating protein 2 is highly expressed in medullary thyroid carcinoma patients and is a poor prognostic biomarker of disease-free survival of medullary thyroid carcinoma patients.

Chemical Composition of Tobacco Seed Oils and Their Antioxidant, Anti-Inflammatory, and Whitening Activities.

Tobacco seeds are a valuable food oil resource, and tobacco seed oil is rich in nutrients, especially polyunsaturated fatty acids. The aim of this work was to perform a comprehensive study on the chemical constituents, and the antioxidant, anti-inflammatory, and whitening activities of tobacco seed oils (NC89 and BS4). A GC/MS analysis revealed that NC89 and BS4 had 11 and 6 volatile compounds, respectively. The PUFA contents in NC89 and BS4 were 74.98% and 72.84%, respectively. These two tobacco seed oils also presented good radical scavenging capacities with the neutralization of ABTS, OH-, and superoxide (O2-) radicals in a concentration-dependent manner. Meanwhile, NC89 and BS4 inhibited reactive oxygen species (ROS) accumulation and cell apoptosis, enhanced SOD and CAT activities, and increased the GSH content in H2O2-induced HepG2 cells. In addition, NC89 and BS4 exhibited significant anti-inflammatory activities by inhibiting the expressions of NO, TNF-α, IL-1ß, and IL-6 in LPS-induced RAW.264.7 cells through the regulation of the MAPK signaling pathway. Moreover, NC89 and BS4 expressed whitening activities by inhibiting tyrosinase activity and intracellular melanin production. Therefore, tobacco seed oils could be used as an important oil resource for the development of high value-added products.

Effects of IL-17 on expression of GRO-α and IL-8 in fibroblasts from nasal polyps.

Recent studies indicated that interleukin (IL)-17, growth-related oncogene (GRO)-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.

Isopropylmalate synthase NtIPMS as a potential molecular marker for seed vigor in tobacco.

Seed vigor is an important trait for tobacco production. However, the evaluation of seed vigor using molecular biomarkers is scarcely reported in tobacco. In this study, the development of molecular marker isopropylmalate synthase NtIPMS was conducted to detect seed ageing degree and seed priming effect in tobacco. Quantitative real-time PCR (qRT-PCR) analysis showed that the expression of NtIPMS was significantly induced at the initial imbibition stage during seed germination. The NtIPMS expression was positively correlated with the degree of seed ageing in non-pelleted and pelleted seeds. The mRNA level of NtIPMS was gradually increased with the increasing degree of seed ageing. The early best effect of gibberellin priming was observed in 30-h primed seeds, and the highest expression of NtIPMS was observed in 12-h primed seeds. The best stop time-point of seed priming is likely at the time 18 h after the relatively higher NtIPMS expression occurred during seed priming process. The NtIPMS mRNA detection has the potential usage as a potential molecular marker for the evaluation of seed vigor in tobacco.

Advances in the Understanding of Reactive Oxygen Species-Dependent Regulation on Seed Dormancy, Germination, and Deterioration in Crops.

Reactive oxygen species (ROS) play an essential role in the regulation of seed dormancy, germination, and deterioration in plants. The low level of ROS as signaling particles promotes dormancy release and triggers seed germination. Excessive ROS accumulation causes seed deterioration during seed storage. Maintaining ROS homeostasis plays a central role in the regulation of seed dormancy, germination, and deterioration in crops. This study highlights the current advances in the regulation of ROS homeostasis in dry and hydrated seeds of crops. The research progress in the crosstalk between ROS and hormones involved in the regulation of seed dormancy and germination in crops is mainly summarized. The current understandings of ROS-induced seed deterioration are reviewed. These understandings of ROS-dependent regulation on seed dormancy, germination, and deterioration contribute to the improvement of seed quality of crops in the future.

Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 Possesses Prognostic Significance and Promotes Progression of Papillary Thyroid Cancer.

PURPOSE: Identification of novel biomarkers could benefit the clinical therapy and management of papillary thyroid carcinoma (PTC). Human endogenous retrovirus long terminal repeat-associating protein 2 (HHLA2) has been reported to play roles in the development of various cancers. The clinical significance and biological function of HHLA2 in PTC were investigated. PATIENTS AND METHODS: The expression level of HHLA2 was evaluated in PTC tissues (from 107 PTC patients) and cell lines (TPC-1, IHH-4, CGTH-W3, and MDA-T32 cells) by RT-qPCR. The clinical significance of HHLA2 was estimated with a series of statistical analyses. The biological function of HHLA2 was assessed with the CCK8 assay and transwell assay. RESULTS: HHLA2 was upregulated in PTC compared with the normal samples and was associated with the positive lymph node metastasis and advanced TNM stage of PTC patients. HHLA2 was an independent prognostic factor associated with the poor survival of PTC patients. Additionally, HHLA2 functioned as a tumor promoter that enhanced the progression of PTC cells. CONCLUSION: HHLA2 could serve as a prognostic biomarker and tumor promoter in PTC, providing a novel therapeutic target of PTC.

Ethyl pyruvate attenuates murine allergic rhinitis partly by decreasing high mobility group box 1 release.

High-mobility group box 1 (HMGB1) protein, a pro-inflammatory DNA-binding protein, meditates inflammatory responses through Toll-like receptor-4 signals and amplifies allergic inflammation by interacting with the receptor for advanced glycation end products. Previous studies have shown that HMGB1 is elevated in the nasal lavage fluids (NLF) of children suffering from allergic rhinitis (AR) and is associated with the severity of this disease. Furthermore, HMGB1 has been implicated in the pathogenesis of lower airway allergic diseases, such as asthma. Ethyl pyruvate (EP) has proven to be an effective anti-inflammatory agent for numerous airway diseases. Moreover, EP can inhibit the secretion of HMGB1. However, few studies have examined the effect of EP on AR. We hypothesized that HMGB1 plays an important role in the pathogenesis of AR and studied it using an AR mouse model. Forty BALB/c mice were divided into four groups: the control group, AR group, 50 mg/kg EP group, and 100 mg/kg EP group. The mice in the AR and EP administration groups received ovalbumin (OVA) sensitization and challenge, whereas those in the control group were given sterile saline instead of OVA. The mice in the EP administration group were given an intraperitoneal injection of EP 30 min before each OVA treatment. The number of nasal rubbings and sneezes of each mouse was counted after final treatment. Hematoxylin-eosin staining, AB-PAS staining, interleukin-4 and 13 in NLF, IgE, and the protein expression of HMGB1 were measured. Various features of the allergic inflammation after OVA exposure, including airway eosinophilia, Th-2 cytokine production, total IgE, and goblet cell hyperplasia were significantly inhibited by treatment with EP and the expression and release of HMGB1 were reduced after EP administration in a dose-dependent manner. These results indicate that HMGB1 is a potential therapeutic target of AR and that EP attenuates AR by decreasing HMGB1 expression.

[Refractory chronic rhinosinusitis and bacterial biofilm].

Chronic rhinosinusitis (CRS) is a common disease in otolaryngology, and with the development of the therapy technology, most of the cases have reached a cure. But there are still some intractable cases in clinic, signs and symptoms of chronic rhinosinusitis of which still persist after the standardized drugs and technically adequate endoscopic sinus surgery, and this part is clinically named refractory chronic rhinosinusitis (RCRS). In recent studies of the pathogenesis of RCRS, bacterial biofilm (BBF) is attracting more attention. The main emphasis of this review will be to highlight the biological characteristics of BBF, the relationship of BBF and CRS and treatment strategies of BBF positive CRS.