Genetic Diversity, Regional Distribution, and Clinical Characteristics of Severe Fever with Thrombocytopenia Syndrome Virus in Gangwon Province, Korea, a Highly Prevalent Region, 2019-2021.

Severe fever with thrombocytopenia syndrome (SFTS) is an arthropod-borne viral disease with a high mortality rate with high fever and thrombocytopenia. We investigated the clinical and epidemiological characteristics and viral genotypes from 2019 to 2021 in Gangwon Province, Korea. Of the 776 suspected cases, 62 were SFTS. The fatality rate was 11.5-28.6% (average rate, 19.4%), and the frequent clinical symptoms were high fever (95.2%), thrombocytopenia (95.2%), and leukopenia (90.3%). Hwacheon had the highest incidence rate per 100,000 persons at 8.03, followed by Inje and Yanggu (7.37 and 5.85, respectively). Goseong, Yangyang, and Hoengseong had rates of 2 or higher; Samcheok, Hongcheon, Jeongsen, and Yeonwol were 1.70-1.98, and Wonju, Gangneung, and Donghae were slightly lower, ranging from 0.31 to 0.74. Of the 57 cases with identified genotypes, eight genotypes (A, B1, B2, B3, C, D, E, and F) were detected, and the B2 genotype accounted for 54.4% (31 cases), followed by the A genotype at 22.8% (13 cases). The B2 and A genotypes were detected throughout Gangwon Province, and other genotypes, B1, B3, C, D, and F, were discovered in a few regions. In particular, genotype A could be further classified into subtypes. In conclusion, SFTS occurred throughout Gangwon Province, and Hwacheon had the highest incidence density. Multiple genotypes of SFTS were identified, with B2 and A being the most common. These findings provide important insights for the understanding and management of SFTS in this region.

Role of DDX53 in taxol-resistance of cervix cancer cells in vitro.

Cancer/Testis antigen DDX53 shows high expression level in various tumors and is involved in anti-cancer drug resistance. However, the functional study of DDX53 in cervix cancer remains unknown. In this study, the role of DDX53 in taxol-resistance of cervix cancer cells was investigated. In taxol-resistant HelaTR cells, DDX53 was significantly increased as compared to the parental HeLa cells. HelaTR cells also showed upregulation of multidrug resistant gene MDR1, invasive characteristics and decreased apoptosis. In addition, increased autophagy level was observed in HelaTR cells. Overexpression of DDX53 in HeLa and SiHa markedly led to greater resistance to taxol and cisplatin, whereas knockdown of DDX53 in HelaTR cells restored sensitivity, demonstrating that DDX53 regulated taxol resistance in cervix cancer cells. DDX53 overexpression in HeLa and SiHa cells enhanced invasion, migration and anchorage independent growth, DDX53 knockdown showed inverse effects in HeLaTR cells. When DDX53 expression was suppressed by siRNA, autophagic flux and drug resistance of HelaTR cells were decreased. In addition, DDX53 was upregulated in cervix cancer tissues from patient with a glassy cell carcinoma of cervix. Taken together, these results suggest that DDX53 plays a critical role in taxol-resistance by activating autophagy and a potential therapeutic target for the treatment of taxol-resistant cervix cancer.

Integrated microfluidics platforms for investigating injury and regeneration of CNS axons.

We describe the development of experimental platforms to quantify the regeneration of injured central nervous system (CNS) neurons by combining engineering technologies and primary neuronal cultures. Although the regeneration of CNS neurons is an important area of research, there are no currently available methods to screen for drugs. Conventional tissue culture based on Petri dish does not provide controlled microenvironment for the neurons and only provide qualitative information. In this review, we introduced the recent advances to generate in vitro model system that is capable of mimicking the niche of CNS injury and regeneration and also of testing candidate drugs. We reconstructed the microenvironment of the regeneration of CNS neurons after injury to provide as in vivo like model system where the soluble and surface bounded inhibitors for regeneration are presented in physiologically relevant manner using microfluidics and surface patterning methods. The ability to control factors and also to monitor them using live cell imaging allowed us to develop quantitative assays that can be used to compare various drug candidates and also to understand the basic mechanism behind nerve regeneration after injury.

Quantitative analysis of axonal transport by using compartmentalized and surface micropatterned culture of neurons.

Mitochondria, synaptic vesicles, and other cytoplasmic constituents have to travel long distance along the axons from cell bodies to nerve terminals. Interruption of this axonal transport may contribute to many neurodegenerative diseases including Alzheimer's disease (AD). It has been recently shown that exposure of cultured neurons to ß-amyloid (Aß) resulted in severe impairment of mitochondrial transport. This Letter describes an integrated microfluidic platform that establishes surface patterned and compartmentalized culture of neurons for studying the effect of Aß on mitochondria trafficking in full length of axons. We have successfully quantified the trafficking of fluorescently labeled mitochondria in distal and proximal axons using image processing. Selective treatment of Aß in the somal or axonal compartments resulted in considerable decrease in mitochondria movement in a location dependent manner such that mitochondria trafficking slowed down more significantly proximal to the location of Aß exposure. Furthermore, this result suggests a promising application of microfluidic technology for investigating the dysfunction of axonal transport related to neurodegenerative diseases.

Novel microfluidic platform for culturing neurons: culturing and biochemical analysis of neuronal components.

Neurons, one of the most polarized types of cells, are typically composed of cell bodies (soma), dendrites, and axons. Many events such as electric signal transmission, axonal transport, and local protein synthesis occur in the axon, so that a method for isolating axons from somata and dendrites is required for systematically investigating these axonal events. Based on a previously developed neuron culture method for isolating and directing the growth of central nervous system axons without introducing neutrophins, we report three modified microfluidic platforms: (1) for performing biochemical analysis of the pure axonal fraction, (2) for culturing tissue explants, and (3) a design that allows high content assay on same group of cells. The key feature of these newly developed platforms is that the devices incorporate a number of microgrooves for isolating axons from the cell body. They utilize an open cellculture area, unlike the enclosed channels of the previous design. This design has extended the axonal channel so that a sufficient amount of pure axonal fraction can be obtained to perform biochemical analysis. The design also addresses the drawback of the previous neuron culture device, which was not adaptable for culturing thick neuronal tissues such as brain explants, neurospheres, and embryoid bodies, which are essential model tissues in neuroscience research. The design has an open cellculture area in the center and four enclosed channels around open area, and is suitable for multiple drug screening assays.