microRNA-599 promotes apoptosis and represses proliferation and epithelial-mesenchymal transition of papillary thyroid carcinoma cells via downregulation of Hey2-depentent Notch signaling pathway.

Although papillary thyroid carcinoma (PTC) has a favorable prognosis after surgical or medical treatment, its survival rate is still very low. Therefore, finding more reliable therapy methods to limit PTC is a necessity. Compelling evidence has implicated the role of microRNAs (miRNAs or miRs) in PTC. This study aims at investigating the possible effect of microRNA-599 (miR-599) on proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of PTC cells by targeting Hey2 gene. Differentially expressed genes/miRNAs associated with PTC were screened based on microarray analysis. Then, the expression of the candidate gene, as well as, the regulatory miRNA were detected in PTC cells, the related signaling pathway was verified. Afterward, the relationship between the miR and the candidate gene was verified by dual-luciferase reporter gene assay. Subsequently, the effects of overexpressed miR and silenced candidate gene on cell proliferation, cell apoptosis, EMT, migration, and invasion were detected. In PTC tissues and cells, miR-599 was downregulated while Hey2 expressed highly. Hey2 is a target gene of miR-559. In addition, the expression of Bax and E-cadherin was elevated while that of Hey2, Notch1, Delta-like1, Hes1, N1ICD, Jagged1, Snail, Slug, N-cadherin and Vimentin, and Bcl-2 was reduced in cells treated with upregulated miR-599 or downregulated Hey2. Moreover, miR-599 overexpression or Hey2 silencing inhibited cell proliferation, migration, invasion, along with EMT but promoted apoptosis. This study verified that miR-599 promotes apoptosis and represses proliferation, EMT of PTC cells through inactivating the Notch signaling pathway by downregulating Hey2, which has great clinical significance for PTC treatment.

Overexpression of long noncoding RNA SLC26A4-AS1 inhibits the epithelial-mesenchymal transition via the MAPK pathway in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is recognized as one of the most prevalent types of thyroid cancer with poor prognosis. Long noncoding RNA (lncRNA) has undergone an intensive study for their involvement in tumor treatment. This study intends to unravel the association of lncRNA SLC26A4-AS1 with PTC. Initially, PTC-related expression profiling data (GSE33630) was utilized to screen differentially expressed lncRNAs in PTC and the underlying mechanisms involved with the mitogen-activated protein kinase (MAPK) pathway. Moreover, PTC tumor tissues and paracancerous tissues were arranged to determine expressions of TP53, SLC26A4-AS1, and genes related to epithelial-mesenchymal transition (EMT) and the MAPK pathway. Furthermore, SLC26A4-AS1 was overexpressed or underexpressed and JNK was underexpressed through cell transfection to examine the effect of SLC26A4-AS1 on PTC via MAPK pathway. Besides, tumor formation in nude mice was used to verify the fore experiment. LncRNA SLC26A4-AS1 regulating TP53 had the potential to participate in PTC by regulating the MAPK pathway. SLC26A4-AS1 was expressed poorly in PTC. Notably, SLC26A4-AS1 elevated E-cadherin expression while it reduced that of ERK and Vimentin. In addition, the overexpression of SLC26A4-AS1 inactivated the MAPK pathway by promoting TP53 and decreased cell migration, proliferation, and invasion. In addition to all these effects, the overexpression of SLC26A4-AS1 promoted apoptosis of TPC-1 cells. Additionally, the overexpression of lncRNA SLC26A4-AS1 reduced xenograft tumor volume in nude mice. Furthermore, the effect of SLC26A4-AS1 overexpression was found to be promoted after the MAPK pathway inactivation. Taken together, the overexpression of lncRNA SLC26A4-AS1 coffered anti-oncogenic effects on PTC through the inactivation of the MAPK pathway.

Cytochrome b5 reductase 2 is a novel candidate tumor suppressor gene frequently inactivated by promoter hypermethylation in human nasopharyngeal carcinoma.

Cytochrome b5 reductase 2 (CYB5R2), a member of the flavoprotein pyridine nucleotide cytochrome reductase family, is associated with a number of physiological reactions. However, its role in cancer, especially nasopharyngeal carcinoma (NPC), has not been addressed. Here, we investigate the transcript levels and promoter methylation status of CYB5R2 in NPC derived cell lines and tumor biopsies and experimentally address its role as a tumor suppressor gene. We find that CYB5R2 transcript levels are decreased in NPC cell lines and tumor biopsies. Promoter hypermethylation of CYB5R2 was detected in all six tested NPC cell lines and in 84% of primary NPC tumor biopsies but not in normal nasopharyngeal epithelium. Clinically, CYB5R2 methylation was associated with lymph node metastasis in NPC patients (P < 0.05). The endogenous expression of CYB5R2 could be restored in vitro by the methyltransferase inhibitor 5-aza-2'-deoxycytidine in NPC cell lines. Ectopic expression of CYB5R2 had an inhibitory effect on proliferation, clonogenicity and migration of NPC cells. Moreover, in vivo tests in nude mice indicated that ectopic expression of CYB5R2 reduces the tumorigenicity of CYB5R2-negative NPC cells. Collectively, these findings suggest that CYB5R2 may be a functional tumor suppressor gene, frequently inactivated by hypermethylation of its promoter in NPC. We report here the first instance of epigenetic downregulation in NPC tumor biopsies of a key enzyme, CYB5R2, which is responsible for the detoxification of environmental carcinogens. We propose the possibility of utilizing CYB5R2 promoter methylation as a diagnostic biomarker of NPC in the future.

Lithium-Ion-Sieve-Embedded Hybrid Membranes for Anion-Exchange- and Cation-Concentration-Driven Li/Mg Separation.

There is an urgent need to develop efficient and environmentally friendly technologies for separating Li+ from brines containing abundant Mg2+ to meet the growing demand for lithium resources. In this work, we prepared hybrid membranes by integrating hydrogen manganese oxide (HMO), a lithium-ion sieve, as a filler into anion-exchange membranes (AEMs), the quaternary ammonium-functionalized poly(2,6-dimethyl-1,4-phenylene oxide) (QPPO) and poly(m-terphenyl piperidinium) (m-PTP). Cations are transported by electrostatic attraction originating from anions and the concentration difference across membranes. Because of the effects of electrostatic repulsion of the fixed cationic groups and steric resistance in AEMs, Li+ with less charge and smaller radius will preferentially pass through the membrane. In addition, the presence of HMO provides an additional fast transport channel for Li+, resulting in an enhanced Li+/Mg2+ separation performance. The results show that 20%HMO@m-PTP exhibits high Li+ flux (0.48 mol/m2·h) and Li+/Mg2+ selectivity (ßLi+/Mg2+ = 14.1). Molecular dynamics simulations show that m-PTP has more free volume than QPPO, which is beneficial for rapid cation transport. Spectral analysis confirms the insertion and sieving of Li+ in HMO. This work illustrates the great potential of anion-exchange- and cation-concentration-driven hybrid membranes based on lithium-ion sieves for low-energy and efficient Li+ extraction processes.

Polymer Inclusion Membranes with P507-TBP Carriers for Lithium Extraction from Brines.

The separation of lithium and magnesium from salt-lake brines with high Mg2+/Li+ ratios is a main challenge for lithium extraction. In this work, novel polymer inclusion membranes (PIMs) were developed by incorporating 2-ethylhexyl phosphonic acid mono 2-ethylhexyl (P507) and tributyl phosphate (TBP) as the carriers into cellulose triacetate (CTA) polymers. The Li+ could be stripped from the P507-TBP extracting carriers using pure water eluents without adding concentrated hydrochloric acid, which can help decrease carriers' leakage risk from membrane matrixes and keep the stability of PIMs. The morphology, composition, and wettability of P507-TBP-based PIMs were characterized systematically, and the carrier content in the PIM was also optimized. In the transport experiment with the feed of 0.1 mol/L LiCl and 4.0 mol/L MgCl2, the CTA/P507-TBP60% membrane exhibits a Li+ permeability of 4.76 × 10−3 mol·m−2·h−1 and a Li/Mg separation ratio of 10.2. After recycling seven times, the selectivity of the PIM is well-retained (>10), and the permeability of Li+ decreases slightly (less than 15%). With a decent selectivity and excellent stability, PIMs containing P507-TBP carriers show great potential for sustainable and efficient lithium recovery from brines with high Mg/Li ratios.

Epigenetic inactivation of follistatin-like 1 mediates tumor immune evasion in nasopharyngeal carcinoma.

Follistatin like-1 (FSTL1) is a secreted glycoprotein involved in a series of physiological and pathological processes. However, its contribution to the development of cancer, especially the pathogenesis of nasopharyngeal carcinoma (NPC), remains to be elucidated. We aimed to investigate the dysregulation of FSTL1 and its possible function in NPC. FSTL1 was frequently downregulated in NPC cell lines and primary tumor biopsies by promoter hypermethylation. Ectopic expression of FSTL1 significantly suppressed the colony formation, proliferation, migration and invasion ability of NPC cells and induced cell apoptosis. Overexpression of FSTL1 decreased the tumorigenicity of NPC cells in vivo. In addition, the proliferation of NPC cells in vitro was inhibited by treatment with soluble recombinant FSTL1 protein. The protein level of FSTL1 was decreased in primary NPC tumors and was associated with downregulated interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α). Furthermore, recombinant human FSTL1 protein induced secretion of IL-1ß and TNF-α in macrophage cultures, therefore FSTL1 might activate macrophages and attenuate the immune evasion of NPC cells. In conclusion, the epigenetic downregulation of FSTL1 may suppress the proliferation and migration of NPC cells, leading to dysfunctional innate responses in surrounding macrophages.

[The management of thyroid well-differentiated carcinoma invading the upper aerodigestive tract].

OBJECTIVE: To investigate the management and prognosis of thyroid well-differentiated carcinoma invading the upper aerodigestive tract. METHODS: A retrospective analysis of the management was performed done 62 patients with thyroid well-differentiated carcinoma invading the upper aerodigestive tract. The main method of surgery was shaving excision, and the other means including partial thyrochondrectomy, total laryngectomy, sleeve tracheal resection, sternocleidomastoid myoperiosteal flap and myodermal flap reconstruction, or simply palliative excision. Some patients received postoperative radioactive isotope therapy and radiotherapy. All patients were followed-up for 2 to 15 years with an average of 6.5 years. RESULTS: The best curative effect was proved in the patients with local invasion, with the lumen uninvolved and their locoregional control rate was 100.0% (17/17). And the second choice was in patients with more extensive involvement of the upper aerodigestive tract structures. For them, extensive surgical management was done attempting to remove all gross disease followed by reconstruction, their locoregional control rate was 87.5% (7/8). And the third place was designated to patients with local invasion for which shaving excision was performed even though minor residual disease was left, their locoregional control rate was 55.6% (5/9). The poorest result went to simple palliative excision. For 17 patients with minor residual tumor, the locoregional control rate of those who were given postoperative radioactive isotope therapy was significantly higher than those without. CONCLUSION: According to the limits and degree of invasion in the upper aerodigestive tract by thyroid well-differentiated carcinoma, different ways of surgery is indicated. For patients with residual disease, radioactive isotope therapy should be used to improve the result and life quality. Advanced lesions should be given postoperative radio therapy.

Prognostic value of pretreatment serum levels of lactate dehydrogenase in nonmetastatic nasopharyngeal carcinoma: single-site analysis of 601 patients in a highly endemic area.

BACKGROUND: Numerous studies have generated promising but incomplete evidence for the prognostic value of pretreatment serum levels of lactate dehydrogenase (S-LDH) in nasopharyngeal carcinoma (NPC). METHODS: Pretreatment serum levels of S-LDH in 601 patients with NPC were measured before treatment, and their associations with overall survival and tumor-free survival were studied. Univariate and multivariate analysis of subgroups was used to evaluate the prognostic value of S-LDH in early-stage and late-stage NPC separately. RESULTS: Pretreatment S-LDH levels were significantly lower in T1+2 patients than in T3+4 patients, lower in N0+1 patients than in N2+3 ones, and lower in stage I + II patients than in III + IV ones. Multivariate analysis showed that among patients with late-stage NPC, high pretreatment S-LDH levels >225 U/L were an independent predictor of poor overall survival and tumor-free survival. Among patients with early-stage NPC, pretreatment S-LDH levels >171 U/L, which overlap with the normal range, were an independent predictor of shorter overall survival and tumor-free survival. CONCLUSION: Pretreatment S-LDH levels may be a reliable biomarker for predicting the long-term prognosis of patients with early-stage or late-stage NPC.

Prognostic value of the pretreatment serum level of cytokeratin fraction 21-1 in undifferentiated nasopharyngeal carcinoma: a study of 332 cases.

BACKGROUND: Prognostic value of serum cytokeratin fraction 21-1 (CYFRA 21-1) has not been fully validated for nasopharyngeal carcinoma (NPC). METHODS: Serum CYFRA 21-1 levels of 332 patients with NPC were measured before treatment, and their association with overall survival (OS), tumor-free survival (TFS), time to local recurrence (TLR), and time to distant recurrence (TDR) was studied. RESULTS: Pretreatment serum CYFRA 21-1 level of patients with classification of T1+2 , N0 , stage I+II was significantly lower than that of those with T3+4 , N1+2+3 and III+IV, respectively. Multivariate analysis showed that a high pretreatment serum level of CYFRA 21-1 and T classification were independent predictors of poor OS and TDR. A high pretreatment level of CYFRA 21-1 was an independent predictor of shorter TFS and TLR. CONCLUSION: The pretreatment serum level of CYFRA 21-1 would be a reliable biomarker to evaluate the long-term prognosis of patients with undifferentiated NPC.

Maillard reaction products from chitosan-xylan ionic liquid solution.

A facile method is reported to prepare Maillard reaction products (MRPs) from chitosan and xylan in co-solvent ionic liquid. UV absorbance and fluorescence changes were regarded as indicators of the occurrence of Maillard reaction. FT-IR, NMR, XRD and TG were used to investigate the structure of chitosan-xylan conjugate. The results revealed that when chitosan reacted with xylan in ionic liquid, the hydrogen bonds in chitosan were destroyed, the facts resulted in the formation of chitosan-xylan MRPs. Moreover, when the mass ratio of chitosan to xylan was 1:1, the Maillard reaction proceeded easily. In addition, relatively high antioxidant property was also noted for the chitosan-xylan conjugate with mass ratio 1:1. So the obtained chitosan-xylan MRP is a promising antioxidant agent for food industry.

Rapid exfoliation of rectorite in quaternized carboxymethyl chitosan.

Exfoliated quaternized carboxymethyl chitosan/rectorite (QCMC/REC) nanocomposite was prepared via microwave irradiation method for 70 min, which was performed in only water without any additional plasticizer. XRD, TEM, AFM, SEM and FTIR results revealed that when the mass ratio of QCMC to REC was no less than 4:1, the silicate layers of REC were completely exfoliated in QCMC matrix and were homogenous with QCMC, the surface of QCMC/REC nanobiocomposite was very smooth; two types of interactions of hydrogen bond and electrostatic attraction existed in the QCMC/REC nanobiocomposite. Thermal analysis indicated that QCMC/REC nanobiocomposite had higher thermal stability than only QCMC. Therefore, the microwave irradiation method appears to be a promising tool for preparing exfoliated biopolymer/layered silicate nanocomposites at a mild condition.

Radiation-induced sarcoma in the head and neck region: a clinicopathologic and immunohistochemical study of 13 cases.

OBJECTIVES: To study the clinical and histological features of radiation-induced sarcoma in the head and neck (RISHN). METHODS: Medical records of 13 patients with RISHN treated at our institution between 1990 and 2011 were studied, and paraffin-embedded samples were analyzed by haematoxylin and eosin staining and immunohistochemistry to determine mitosis counts and assess expression of Ki-67, bcl-2, and survivin. RESULTS: Positive bcl-2 was observed in 12 (100%) and survivin in 10 (76.9%) patients. The Ki-67 labeling index ranged from 1% to 90%, and it showed significant positive correlation with mitosis count in RISHN tissues, based on Spearman analysis. Percentage of distal metastasis with T2b was significantly higher than T1b stage (P=0.035). CONCLUSIONS: Stage T2b may be a useful indicator for predicting distant metastasis of RISHN. The MIB-1 score may be used as a histological grading system for RISHN. In addition, bcl-2 and survivin protein may play an important role in pathogenesis and progression of RISHN.