MiR-205-5p/GGCT Attenuates Growth and Metastasis of Papillary Thyroid Cancer by Regulating CD44.

Papillary thyroid cancer (PTC) remains the most common endocrine malignancy, despite marked achieves in recent decades, and the mechanisms underlying the pathogenesis and progression for PTC are incompletely elucidated. Accumulating evidence show that γ-glutamylcyclotransferase (GGCT), an enzyme participating in glutathione homeostasis and is elevated in multiple types of tumors, represents an attractive therapeutic target. Using bioinformatics, immunohistochemistry, qRT-PCR, and Western blot assays, we found that GGCT expression was upregulated in PTC and correlated with more aggressive clinicopathological characteristics and worse prognosis. GGCT knockdown inhibited the growth and metastasis ability of PTC cells both in vitro and in vivo and reduced the expression of mesenchymal markers (N-cadherin, CD44, MMP2, and MMP9) while increasing epithelial marker (E-cadherin) in PTC cells. We confirmed binding of microRNA-205-5p (miR-205-5p) on the 3'-UTR regions of GGCT by dual-luciferase reporter assay and RNA-RNA pull-down assay. Delivery of miR-205-5p reversed the pro-malignant capacity of GGCT both in vitro and in vivo. Lastly, we found that GGCT interacted with and stabilized CD44 in PTC cells by co-immunoprecipitation and immunohistochemistry assays. Our findings illustrate a novel signaling pathway, miR-205-5p/GGCT/CD44, that involves in the carcinogenesis and progression of PTC. Development of miR-205-mimics or GGCT inhibitors as potential therapeutics for PTC may have remarkable applications.

S100A1 is a Potential Biomarker for Papillary Thyroid Carcinoma Diagnosis and Prognosis.

S100 calcium binding protein A1 (S100A1) is an important member of the S100 family and known to express in a variety of cancers. However, the biological functions of S100A1 in thyroid carcinoma have not been thoroughly studied. In this report, bioinformatics analyses and immunohistochemistry assays were applied to assess the expression profile of S100A1 as well as its relationship with the pathological features and prognosis of papillary thyroid carcinoma (PTC). Meanwhile, functions of S100A1 in PTC cells were analyzed with either in vitro or in vivo experiments. S100A1 was significantly up-regulated in PTC tissues compared with adjacent non-cancerous tissues. S100A1 protein expression was significantly associated with tumor size (p=0.0032) or lymph node metastasis (p=0.0331). More importantly, an elevated S100A1 expression was significantly correlated with a worse recurrence-free survival (RFS) (HR=2.26, p=0.042). Further, knockdown of S100A1 dramatically inhibited cell proliferation and migration as well as increased apoptosis of PTC cells. S100A1 knockdown inhibited tumor progression as seen in in vivo experiments. In terms of mechanism, down-regulation of S100A1 induced yes associated protein (YAP) phosphorylation in the cytoplasm and diminished Hippo/YAP pathway activation. Therefore, S100A1 may serve as a novel oncogene and a promising biomarker for PTC diagnosis and prognosis.

[An open-label, multicentric clinical trial to evaluate the efficacy and impact on bone metabolism of recombinant human tumor necrosis factor-α receptor II IgG Fc fusion protein with methotrexate in active rheumatoid arthritis: 24-week clinical and radiographic results from ReABLE study].

OBJECTIVE: To evaluate the efficacy, radiographic changes and safety of the combination of recombinant human tumor necrosis factor-α receptor II IgG Fc fusion protein (rhTNFR:Fc) and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: 30 RA patients were treated with rhTNFR:Fc (25 mg subcutaneously twice weekly) and oral MTX (up to 15 mg weekly) in an open-label manner. Clinical response was assessed by American College of Rheumatology (ACR) criteria and Disease Activity Score in 28 joints (DAS28). Radiographs of hands and wrist were assessed by the modified Sharp score. RESULTS: At Week 24, ACR20, ACR50 and ACR70 responses were achieved by 90%, 76.67% and 46.67% respectively. At Week 24, the mean DAS28 was 3.65 ± 1.26 versus 6.41 ± 0.61 at baseline (P < 0.001). And 20% patients achieved remission and 16.67% patients had a low disease activity. At week 24, EULAR good and moderate responses were attained by 36.67% and 60% respectively. Similarly, Health Assessment Questionnaire (HAQ) improved significantly, declining from 1.12 at baseline to 0.36 at week 24 (P < 0.001). No radiographic progression (based on change of total Sharp score) was found in 27 cases. Adverse events were mild. CONCLUSION: rhTNFR:Fc in combination with MTX shows an excellent efficacy of reduced disease activity, improved function and slowed radiographic progression through 24 weeks. A combination therapy for 24 weeks can lead to disease remission and an inhibition of radiographic progression. Further study is warranted.

The crystal structure and photocatalytic properties of a three-dimensional cadmium(II) metal-organic framework: poly[bis(µ3-benzene-1,2-dicarboxylato)[µ2-1,4-bis(pyridin-3-ylmethoxy)benzene]dicadmium(II)].

Photocatalysis is a green technology for the treatment of all kinds of contaminants and has advantages over other treatment methods. Recently, much effort has been devoted to developing new photocatalytic materials based on metal-organic frameworks for use in the degradation of many kinds of organic contaminants. With the aim of searching for more effective photocatalysts, the title three-dimensional coordination polymer, [Cd2(C8H4O4)2(C18H16N2O2)]n, was prepared. The asymmetric unit contains one Cd(II) cation, one benzene-1,2-dicarboxylate anion (denoted L(2-)) and half of a centrosymmetric 1,4-bis(pyridin-3-ylmethoxy)benzene ligand (denoted bpmb). Each Cd(II) centre is five-coordinated by four carboxylate O atoms from two L(2-) ligands and by one N atom from a bpmb ligand, forming a disordered pentagonal pyramidal coordination geometry. The Cd(II) centres are interlinked by L(2-) ligands to form a one-dimensional [Cd2L2]n chain. Adjacent chains are further connected by bpmb linkers, giving rise to a two-dimensional network, and these networks are pillared by bpmb to afford a three-dimensional framework with a 3(3).4(2).6(3).7(1).8(1) topology. Each grid in the framework has large channels which are filled mainly by the two other equivalent frameworks to form a threefold interpenetrating net. The compound exhibits relatively good photocatalytic activity towards the degradation of methylene blue in aqueous solution under UV irradiation.

A novel Ag(i)-calix[4]arene coordination polymer for the sensitive detection and efficient photodegradation of nitrobenzene in aqueous solution.

Nitrobenzene (NB) is a widespread and highly toxic organic pollutant in water, and consequently its detection and removal have attracted considerable attention. In the present study, we designed and synthesized a novel coordination polymer, [AgL0.5(NO3)]n (1), {L = 25,26,27,28-tetra[(3-pyridylmethyl)oxy]calix[4]arene}, from AgNO3 and a tetra-pyridyl-functionalized calix[4]arene ligand, which possessed a 2D network based on [Ag4L(NO3)4] units. The 1-modified glassy carbon electrode (1/GCE) exhibited good electrocatalytic activity toward the reduction of NB, offering the selective detection of NB in a wide linear range (1-2450 µM) and a low detection limit (0.62 µM). Furthermore, it displayed excellent photocatalytic activity for the degradation of NB in aqueous solution under UV light. The kinetics of the catalytic degradation reaction and the stability of the catalyst were also studied. These results indicated that compound 1 is a favorable material for the effective determination and degradation of NB, which makes it a promising candidate in both monitoring water quality and treating wastewater.

Association of viral replication capacity with the pathogenicity of enterovirus 71.

Enterovirus 71 (EV71) is a major cause of hand-foot-and-mouth disease, which is associated with fatal neurological disease. The mechanism of EV71 pathogenesis remains obscure. We compared the replication capacity of the severe and mild enterovirus 71 isolates. The replication kinetics of EV71 in RD cells and ICR mice was determined by qRT-PCR. The lung, muscular, brain, intestine tissues were used for histopathological and immunohistochemical assays. The growth curves of EV71 strains in RD cells showed that the severe EV71 strains (SDLY107 and SDLY52) replicated faster and generated more viral RNA than the mild EV71 strains (SDLY11 and SDLY1). The mice infected by the severe EV71 strains (SDLY107) showed more severe clinical symptoms, pathological changes and higher viral load than the mice infected by the mild EV71 strains (SDLY11). These results suggest that there was a difference in replication capacity between the severe and mild EV71 strains, which was possibly associated with EV71 pathogenesis.

[Analysis on Clenbuterol pollution in swine products in Beijing, 2002].

OBJECTIVE: To explore the status of clenbuterol pollution in swine products in Beijing city in 2002. METHODS: European Union method (EUR 15127-EN Cy2.3) was adopted to examine the samples. Samples were screened by enzyme-linked immunosorbent assay (ELISA) and confirmed by GC-MS. Detected limit of the method was 0.5 micro g/kg. Samples, including lung, liver, pork, kidney and urine of swine, were collected from slaughterhouses, refrigeratories and markets in 11 districts of Beijing. RESULTS: The results indicated that 185 out of 1 379 samples were positive with an annual positive rate of 13.4%. The highest was 15.7% in lung of swine, followed by urine 15.2% and pork liver 14.0%. CONCLUSION: Rates of detection had decreased from 30.0% to 2.7% during 2002.