ObjectivesThe outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the Republic of Korea started from the index case who developed fever after returning from the Middle East. He infected 26 cases in Hospital C, and consecutive nosocomial transmission proceeded throughout the nation. We provide an epidemiologic description of the outbreak, as of July 2015.MethodsEpidemiological research was performed by direct interview of the confirmed patients and reviewing medical records. We also analyzed the incubation period, serial interval, the characteristics of superspreaders, and factors associated with mortality. Full genome sequence was obtained from sputum specimens of the index patient.ResultsA total of 186 confirmed patients with MERS-CoV infection across 16 hospitals were identified in the Republic of Korea. Some 44.1% of the cases were patients exposed in hospitals, 32.8% were caregivers, and 13.4% were healthcare personnel. The most common presenting symptom was fever and chills. The estimated incubation period was 6.83 days and the serial interval was 12.5 days. A total of 83.2% of the transmission events were epidemiologically linked to five superspreaders, all of whom had pneumonia at presentation and contacted hundreds of people. Older age [odds ratio (OR) = 4.86, 95% confidence interval (CI) 1.90–12.45] and underlying respiratory disease (OR = 4.90, 95% CI 1.64–14.65) were significantly associated with mortality. Phylogenetic analysis showed that the MERS-CoV of the index case clustered closest with a recent virus from Riyadh, Saudi Arabia.ConclusionA single imported MERS-CoV infection case imposed a huge threat to public health and safety. This highlights the importance of robust preparedness and optimal infection prevention control. The lessons learned from the current outbreak will contribute to more up-to-date guidelines and global health security.

Lung cancer is recently regarded as an overhealed inflammatory disease. Serum amyloid A (SAA) is known as an acute phase protein, but it is likely involved in the cancer pathogenesis. We identified both SAA1 and SAA2 in the pooled sera of lung cancer patients but not in the healthy control, by LC-MS/MS analysis. We found that about 14-fold higher levels of SAA in lung cancer patients' sera and plasma compared to healthy controls by ELISA using total 350 samples (13.89 ± 37.18 vs 190.49 ± 234.70 ug/mL). The SAA levels were also significantly higher than in other pulmonary disease or other cancers. An immunohistochemical study using tissue microarray showed that, unlike other cancer tissues, lung cancer tissues highly express SAA. Further in vitro experiments showed that SAA is induced from lung cancer cells by the interaction with THP-1 monocytes and this, in return, induces MMP-9 from THP-1. In in vivo animal models, overexpressed SAA promoted Lewis lung carcinoma (LLC) cells to metastasize and colonize in the lung. Our data suggest that a higher concentration of SAA can serve as an indicator of lung adenocarcinoma and represents a therapeutic target for the inhibition of lung cancer metastasis.

Small cell lung cancer (SCLC) is an aggressive type of lung cancer, and the detection of SCLCs at an early stage is necessary for successful therapy and for improving cancer survival rates. Fucosylation is one of the most common glycosylation-based modifications. Increased levels of fucosylation have been reported in a number of pathological conditions, including cancers. In this study, we aimed to identify and validate the aberrant and selective fucosylated glycoproteins in the sera of patients with SCLC. Fucosylated glycoproteins were enriched by the Aleuria aurantia lectin column after serum albumin and IgG depletion. In a narrowed down and comparative data analysis of both label-free proteomics and isobaric peptide-tagging chemistry iTRAQ approaches, the fucosylated glycoproteins were identified as up- or down-regulated in the sera of limited disease and extensive disease stage patients with SCLC. Verification was performed by multiple reaction monitoring-mass spectrometry to select reliable markers. Four fucosylated proteins, APCS, C9, SERPINA4, and PON1, were selected and subsequently validated by hybrid A. aurantia lectin ELISA (HLE) and Western blotting. Compared with Western blotting, the HLE analysis of these four proteins produced more optimal diagnostic values for SCLC. The PON1 protein levels were significantly reduced in the sera of patients with SCLC, whereas the fucosylation levels of PON1 were significantly increased. Fucosylated PON1 exhibited an area under curve of 0.91 for the extensive disease stage by HLE, whereas the PON1 protein levels produced an area under curve of 0.82 by Western blot. The glycan structural analysis of PON1 by MS/MS identified a biantennary fucosylated glycan modification consisting of a core + 2HexNAc + 1Fuc at increased levels in the sera of patients with SCLC. In addition, the PON1 levels were decreased in the sera of the Lewis lung carcinoma lung cancer mouse model that we examined. Our data suggest that fucosylated protein biomarkers, such as PON1, and their fucosylation levels and patterns can serve as diagnostic and prognostic serological markers for SCLC.

While the soluble proteins of human teeth consist of various extracellular matrix and bioactive proteins, they have not yet been characterized fully. Moreover, the role they play in tooth regeneration is not clear. Analysis of the soluble proteins in human teeth by liquid chromatography-mass spectrometry revealed 147 different ethylenediaminetetraacetic acid-soluble tooth proteins (ESTPs). Of these, 29 had not been shown previously to be present in human teeth. To determine their effect on the in vitro responses of dental pulp stem cells (DPSCs), DPSCs were cultured in ESTP-coated culture plates and three-dimensional scaffolds. The ESTPs significantly enhanced DPSC odontoblast differentiation and mineralization in vitro, but had only partial effect on bone marrow stem cells or adipose tissue stem cells. To test the effect of ESTPs on in vivo dentin and tooth formation, mouse embryonic tooth-forming primordia and xenogenic murine apical bud epithelium/human DPSC composites were treated with ESTPs before implantation under the renal capsule of ICR mice. ESTP treatment promoted the formation of morphologically normal teeth by the tooth-forming primordium regions and enhanced the development of a regular and large dentin structure by the composites. These observations suggest that human ESTPs contain dentinogenic proteins and can promote dentin and tooth formation.

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