• Journal of fish pathology
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• v.16 no.3
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• pp.175-181
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• 2003

VSNC is a viral disease causing significant economic losses in cultured carp Ciprinus carpio L. in Korea. Carps were immunized with prepared vaccines against VSNCV and examined specific and nonspecific immune responses. Carps were injected by O.2㎖ of formalin-killed vaccine (FKV), heat-killed vaccine (HKV) or E-MEM, respectively and dealt with boost with same way two weeks later. The lysozyme activity of serum and chemiluminescent reponses of head-kidney leucocytes showed increased responses during 2-7 days post-first injection (pfi) and post-boost (pb) in the vaccinated fish, and then decreased to the level of control. As measured by ELISA, vaccinated groups showed a significant increase in VSNCV-specific serum antibodies between 2 weeks pfi and 6weeks pb with a peak at 2 weeks pb. Results of the virus challenge showed that the fish vaccinated with FKV have induced protective immunity, while HKV injection hardly provided protection.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4357-4361
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• 2016

Background: Whether there is any relationship between human papilloma virus (HPV) and breast carcinoma is not clear. Some previous studies have indicated a possible role in oncogenesis in the breast. In this study, we therefore analyzed the presence of HPV infection in breast tissues of Iranian women from Yazd city. Materials and Methods: In a cross-sectional study, formalin-fixed paraffin-embedded tissues from 87 patients with breast cancer and 84 cases with breast fibrocystic lesions (control group) were selected from a tissue archive. Grade of tumors and fibrocystic tissues were determined by two pathologists. The nested-PCR method was performed for detection of HPVs in samples. HPV genotypes were determined by sequencing and the phylogenetic tree depicted by MEGA software. Results: Of the 87 women with breast cancer, 22.9% (20 isolates) had positive results for HPV DNA. In the control group no HPV was detected. The HPV genotypes in positive samples were HPV-16 (35%) HPV-18 (15%), HPV-6 (45%) and HPV-11 (5%). The data did not approved a significant correlation between tissue pathology of breast cancer and the HPV genotype frequency. Conclusions: The data did not provide any evidence for a role of high risk HPV types in oncogenesis in the breast.

• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.101-109
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• 2000

Duck viral hepatitis is an acute, highly infectious viral disease of young dacklings aged from two days to three weeks. The significant lesion associated with the disease was enlarged liver including necrotic foci and numerous hemorrhagic spots. We have isolated five strains of duck hepatitis virus (DHV) from field cases showing about 20% mortality with a sign of opisthotonos. When a-day-old ducklings were intramuscularly inoculated with one of the isolates, 92% of the birds were died within 5 days. We attempted to develop an attenuated strain of duck hepatitis virus (DHV) using one of the isolates by serial chicken embryo passages. The propagation of DHV in chicken embryos was carried 140 passages. The virus titer increased gradually from the $21^{st}$ through the $50^{th}$ passage, but there was no significant increase of virus titer in subsequent passages after then. Through the serial passages, the virulence of the virus for chicken embryos was gradually increased but decreased for ducklings. The pathogenicity of the virus for ducklings was preserved up to the $21^{st}$ passage but disappeared at the $50^{th}$passage. An attenuated Korean isolate which was passaged 140 times in chicken embryos gave good protection in ducklings against both challenge infection to a Korean virulent strain and to a DHV-DRL strain, a type 1 reference strain of DHV, which indicated that the Korean isolates could be classified as DHV type 1. And the above results suggest that an attenuated Korean isolate can be used for developing a live DHV vaccine.

• Clinical and Experimental Pediatrics
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• v.65 no.5
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• pp.230-238
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• 2022

Myocarditis was previously attributed to an epidemic viral infection. Additional harmful reagents, in addition to viruses, play a role in its etiology. Coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis has recently been described, drawing attention to vaccine-induced myocarditis in children and adolescents. Its pathology is based on a series of complex immune responses, including initial innate immune responses in response to viral entry, adaptive immune responses leading to the development of antigen-specific antibodies, and autoimmune responses to cellular injury caused by cardiomyocyte rupture that releases antigens. Chronic inflammation and fibrosis in the myocardium eventually result in cardiac failure. Recent advancements in molecular biology have remarkably increased our understanding of myocarditis. In particular, microRNAs (miRNAs) are a hot topic in terms of the role of new biomarkers and the pathophysiology of myocarditis. Myocarditis has been linked with microRNA-221/222 (miR-221/222), miR-155, miR-10a^*, and miR-590. Despite the lack of clinical trials of miRNA intervention in myocarditis yet, multiple clinical trials of miRNAs in other cardiac diseases have been aggressively conducted to help pave the way for future research, which is bolstered by the success of recently U.S. Food and Drug Administration-approved small-RNA medications. This review presents basic information and recent research that focuses on myocarditis and related miRNAs as a potential novel biomarker and the therapeutics.

• Kidney Research and Clinical Practice
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• v.37 no.4
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• pp.366-372
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• 2018

Background: An inactivated Hantaan virus vaccine (iHV) has been broadly used as a preventive strategy for hemorrhagic fever with renal syndrome (HFRS) by the South Korean Army. After the vaccination program was initiated, the overall incidence of HFRS cases was reduced in the military population. While there are about 400 HFRS cases annually, few studies have demonstrated the efficacy of the iHV in field settings. Therefore, this study aimed to evaluate the iHV efficacy on HFRS severity. Methods: From 2009 to 2017, HFRS cases were collected in South Korean Army hospitals along with patients' vaccination history. HFRS patients were classified retrospectively into two groups according to vaccination records: no history of iHV vaccination and valid vaccination. Vaccine efficacy on the severity of acute kidney injury (AKI) stage and dialysis events were investigated. Results: The effects of the iHV on renal injury severity in between 18 valid vaccinated and 110 non-vaccinated patients were respectively evaluated. In the valid vaccination group, six of the 18 HFRS patients (33.3%) had stage 3 AKI, compared to 60 of the 110 (54.5%) patients in the non-vaccination group. The iHV efficacy against disease progression ($VE_p$) was 58.1% (95% confidence interval, 31.3% to 88.0%). Conclusion: The iHV efficacy against the progression of HFRS failed to demonstrate statistically significant protection. However, different severity profiles were observed between the iHV and non-vaccination groups. Additional studies with larger populations are needed to demonstrate the effectiveness of the iHV in patients with HFRS.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.41.1-41.16
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• 2022

The human antimicrobial peptide LL-37 has chemotactic and modulatory activities in various immune cells, including dendritic cells. Because of its characteristics, LL-37 can be considered an adjuvant for vaccine development. In this study, we confirmed the possible adjuvant activity of LL-37 in mucosal vaccine development against Middle East respiratory syndrome-coronavirus (MERS-CoV) by means of intranasal immunization in C57BL/6 and human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice. Intranasal immunization using the receptor-binding domain (RBD) of MERS-CoV spike protein (S-RBD) recombined with LL-37 (S-RBD-LL-37) induced an efficient mucosal IgA and systemic IgG response with virus-neutralizing activity, compared with S-RBD. Ag-specific CTL stimulation was also efficiently induced in the lungs of mice that had been intranasally immunized with S-RBD-LL-37, compared with S-RBD. Importantly, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to reduced immune cell infiltration into the lungs after infection with MERS-CoV. Finally, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to enhanced protective efficacy, with increased survival and reduced body weight loss after challenge infection with MERS-CoV. Collectively, these results suggest that S-RBD-LL-37 is an effective intranasal vaccine candidate molecule against MERS-CoV infection.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2643-2646
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• 2012

Objectives: Human papillomavirus (HPV) is the major etiological agent of cervical cancer, a leading cause of morbidity and mortality in women worldwide. Screening strategies for reducing the burden of HPV-mediated carcinogenesis are emerging as an effective means for cervical cancer control and prevention in developing countries. Our study, therefore, aimed to identify HPV infection status in North Indian women during random population screening. Methodology: Cervical/vaginal exfoliated cells and/or Pap smear specimens were collected from 890 women of North Indian ethnicity residing in Lucknow and adjoining areas, during random population screening from June 2009-March 2012. HPV viral loads in clinical specimens were determined by the Hybrid Capture (hc)-2 HPV DNA assay, and subsequently, positive/negative/borderline HPV status was calculated. Results: The HPV incidence in the present study was 11.7%. 751 out of a total of 890 women (84.4%) participating in our HPV screening program were HPV negative (HPV -), 104 (11.7%) tested positive (HPV +) while 35 (3.9%) showed borderline (HPV $^*$) infection status. Furthermore, in the HPV + subjects (N=104), 18 (17.3%) showed strong positivity. We observed that HPV positivity tends to increase with age in North Indian women; the higher the viral load with increasing age, higher is the susceptibility to HPV-mediated cervical cancer. Conclusions: HPV viral load/genotyping may help in identifying women at risk of developing cervical cancer. However, cost-effective HPV screening protocols with a wider population coverage are warranted so as to reduce the burden of cervical cancer in women worldwide in the vaccine-era.

• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.291-297
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• 2018

Coxsackievirus B3 (CVB3) is a very well-known causative agent for viral myocarditis and meningitis in human. However, the effective vaccine and therapeutic drug are not developed yet. CVB3 infection activates host cell AKT signaling. Inhibition of AKT signaling pathway may attenuate CVB3 replication and prevent CVB3-mediate viral myocarditis. In this study, we determined antiviral effect of the selected natural plant extract to develop a therapeutic drug for CVB3 treatment. We screened several chemically extracted natural compounds by using HeLa cell-based cell survival assay. Among them, Linum usitatissimum L. extract was selected for antiviral drug candidate. L. usitatissimum extract significantly decreased CVB3 replication and cell death in CVB3 infected HeLa cells with no cytotoxicity. CVB3 protease 2A induced eIF4G1 cleavage and viral capsid protein VP1 production were dramatically decreased by L. usitatissimum extract treatment. In addition, virus positive and negative strand genome amplification were significantly decreased by 1 mg/ml L. usitatissimum extract treatment. Especially, L. usitatissimum extract was associated with inhibition of AKT signal and maintain mTOR activity. In contrast, Atg12 and LC3 expression were not changed by L. usitatissimum extract treatment. In this study, the potential AKT signal inhibitor, L. usitatissimum extract, was significantly inhibited viral genome replication and protein production by inhibition of AKT signal. These results suggested that L. usitatissimum extract is a novel therapeutic agent for treatment of CVB3-mediated diseases.

• Molecules and Cells
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• v.45 no.12
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• pp.896-910
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.7.1-7.19
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• 2024

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×10⁵ plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×10² PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×10² PFU-virus-infected lungs from 2 dpi, but not in 1×10⁵ PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×10⁵ PFU; however, 1×1² PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.