Explore the vast range of titles available.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral infections. To confirm whether HO-1 suppresses SARS-CoV-2 infection, we assessed the antiviral activity of hemin, an effective and safe HO-1 inducer, in SARS-CoV-2 infection. We found that treatment with hemin efficiently suppressed SARS-CoV-2 replication (selectivity index: 249.7012). Besides, the transient expression of HO-1 using an expression vector also suppressed the growth of the virus in cells. Free iron and biliverdin, which are metabolic byproducts of heme catalysis by HO-1, also suppressed the viral infection. Additionally, hemin indirectly increased the expression of interferon-stimulated proteins known to restrict SARS-CoV-2 replication. Overall, the findings suggested that HO-1, induced by hemin, effectively suppressed SARS-CoV-2 in vitro. Therefore, HO-1 could be potential therapeutic candidate for COVID-19.

SARS-CoV-2 induces illness and death in humans by causing systemic infections. Evidence suggests that SARS-CoV-2 can induce brain pathology in humans and other hosts. In this study, we used a canine transmission model to examine histopathologic changes in the brains of dogs infected with SARS-CoV-2. We observed substantial brain pathology in SARS-CoV-2-infected dogs, particularly involving blood-brain barrier damage resembling small vessel disease, including changes in tight junction proteins, reduced laminin levels, and decreased pericyte coverage. Furthermore, we detected phosphorylated tau, a marker of neurodegenerative disease, indicating a potential link between SARS-CoV-2-associated small vessel disease and neurodegeneration. Our findings of degenerative changes in the dog brain during SARS-CoV-2 infection emphasize the potential for transmission to other hosts and induction of similar signs and symptoms. The dynamic brain changes in dogs highlight that even asymptomatic individuals infected with SARS-CoV-2 may develop neuropathologic changes in the brain.

Hepatitis A virus (HAV), the causative pathogen of hepatitis A, induces severe acute liver injuries in humans and is a serious public health concern worldwide. However, appropriate therapeutics have not yet been developed. The enzyme heme oxygenase-1 (HO-1) exerts antiviral activities in cells infected with several viruses including hepatitis B and C viruses. In this study, we demonstrated for the first time the suppression of virus replication by HO-1 in cells infected with HAV. Hemin (HO-1 inducer) induced HO-1 mRNA and protein expression, as expected, and below 50 mM, dose-dependently reduced the viral RNA and proteins in the HAV-infected cells without cytotoxicity. Additionally, HO-1 protein overexpression using a protein expression vector suppressed HAV replication. Although ZnPP-9, an HO-1 inhibitor, did not affect HAV replication, it significantly inhibited hemin-induced antiviral activity in HAV-infected cells. Additionally, FeCl3, CORM-3, biliverdin, and the HO-1 inducers andrographolide and CoPP inhibited HAV replication in the HAV-infected cells; andrographolide and CoPP exhibited a dose-dependent effect. In conclusion, these results suggest that HO-1 effectively suppresses HAV infection in vitro, and its enzymatic products appear to exert antiviral activity. We expect that these results could contribute to the development of a new antiviral drug for HAV.

Here, rabbits were immunized with a virus-like particle (VLP) vaccine prepared by expressing 239 amino acids of the swine hepatitis E virus (HEV)-3 capsid protein using a baculovirus system. Thirty specific-pathogen-free rabbits were divided into five groups (negative and positive control and 10, 50, and 100 μg VLP-vaccinated). Positive control group rabbits showed viremia and fecal viral shedding, whereas rabbits vaccinated with 10 μg VLP showed transient fecal viral shedding, and rabbits vaccinated with 50 and 100 μg VLP did not show viremia or fecal viral shedding. Serum anti-HEV antibody titers increased in a dose-dependent manner. Anti-HEV antibody titers were significantly higher (p < 0.05) in 100 μg VLP-vaccinated rabbits than in the negative control rabbits at week 4. Anti-HEV antibody titers were significantly higher in 50 and 10 μg VLP-vaccinated rabbits than in the negative control rabbits at weeks 8 and 11, respectively. Serum IFN-γ and IL-12 levels were significantly higher (p < 0.01) in rabbits vaccinated with 50 and 100 μg VLP than in the negative control rabbits at weeks 4 and 6. Liver tissues of 50 and 100 μg VLP-vaccinated rabbits displayed significantly less (p < 0.05) fibrosis than those of the positive control rabbits. The prepared VLP vaccine demonstrated dose-dependent immunogenicity sufficient for inducing anti-HEV antibody production, thus protecting rabbits against swine HEV-3.

Torque teno canis virus (TTCaV) is an approximately 2.8 kb circular single-stranded DNA virus known to cause infections in dogs. However, its incidence in Republic of Korea remains unknown. In this study, 135 dog fecal samples were collected to determine TTCaV infection status in Republic of Korea. Based on polymerase chain reaction (PCR) analysis, 13 of 135 (9.6%) dogs tested positive for TTCaV. Three full-length genome sequences (GenBank IDs: MZ503910, MZ503911, and MZ503912) were obtained from the positive specimens. Phylogenetic tree construction and sequence identity, similarity plot, and recombination analyses were performed using these three full-length genomic sequences. Among the three full-length genomes, MZ503912 was determined to be a recombinant virus based on analysis with the reference TTCaV strains. This novel virus strain might have been generated by recombination between TTCaV strain KX827768 discovered in China and MZ503910 discovered in Republic of Korea. This is the first report to determine the incidence, genetic variation, and recombination of TTCaV in dogs in Republic of Korea. Further studies are needed to elucidate TTCaV pathogenesis in dogs.

We investigated the cross-species transmission of rabbit hepatitis E virus (rb HEV) to pigs and evaluated the cross-protection of a swine (sw) HEV-3 virus-like particle (VLP) vaccine against rb HEV infection in pigs. Twelve 4-week-old conventional pigs were divided into negative control (n = 3), positive control (rb HEV-infected, n = 4), and vaccinated (vaccinated and rb HEV-challenged, n = 5) groups. The vaccine was administered at weeks 0 and 2, and viral challenge was conducted at week 4. Serum HEV RNA, anti-HEV antibody, cytokine, and liver enzyme levels were determined. Histopathological lesions were examined in abdominal organs. Viral RNA was detected and increased anti-HEV antibody and alanine aminotransferase (ALT) levels were observed in positive control pigs; liver fibrosis, inflammatory cell infiltration in the lamina propria of the small intestine and shortened small intestine villi were also observed. In vaccinated pigs, anti-HEV antibody and Th1 cytokine level elevations were observed after the second vaccination; viral RNA was not detected, and ALT level elevations were not observed. The results verified the cross-species transmission of rb HEV to pigs and cross-protection of the sw HEV-3 VLP vaccine against rb HEV infection in pigs. This vaccine may be used for cross-protection against HEV infection in other species.

In this study, we generated the HEV virus-like particle (VLP) vaccine expressing 239 amino acids (367–605 aa) of the HEV-3 ORF2 using the baculovirus expression system. The HEV-3-239-VLP vaccine efficacy was evaluated by dividing 12 pathogen-free pigs into four groups: negative control, positive control, 100 μg VLP-, and 200 μg VLP-vaccinated groups for 10 weeks. The pigs in either of the vaccinated groups were administered the corresponding first and booster doses on weeks 0 and 2. At week 4, the positive control and two vaccinated groups were challenged with 106 HEV-3 genomic equivalent copies; viremia and fecal shedding of the virus were identified in pigs in the positive control and 100 μg VLP-vaccinated pigs showed transient viremia and fecal viral shedding. However, no viruses were detected in the serum or fecal samples of the 200 μg VLP-vaccinated pigs. The 100 and 200 μg VLP-vaccinated pigs had significantly higher (p < 0.01) anti-HEV antibodies than the negative control pigs from weeks 6–10 with normal levels of liver enzymes. The 200 μg VLP-vaccinated pigs showed statistically less liver tissue fibrosis (p < 0.05) than that of the positive control pigs. Thus, the novel baculovirus expression system-generated VLP vaccine dose-dependently protects against HEV-3 challenge and may be useful in other animal species, including humans.

Body composition and muscular strength are important for baseball skills and successful performance. Conditioning training programs have the potential to enhance athletic performance via physiological changes. In this single-group interventional study, we investigated the effect of 8 weeks of Pilates training (PT) on contralateral and regional body composition, and isokinetic muscular strength in knee and trunk flexion/extension in adolescent baseball players. In our results, PT increased both right- and left-sided lean mass in the trunk. Following PT, work per repetition and average power showed significant increases in the flexion and extension of the left knee only. PT significantly decreased the peak torque of the trunk flexor and increased the average power of the trunk extensor. In addition, the ratio of the trunk flexion/extension strength of peak torque showed a decreasing trend, whereas that of work and average power did not change significantly following PT. In conclusion, PT evenly improved lean mass on both the right and left sides of the body. Knee and trunk strength increased after PT. Our findings suggest that PT may be a useful strategy for enhancing athletic performance in regard to the muscular strength of adolescent baseball players.

Abstract Canine coronavirus (CCoV), canine parvovirus (CPV), and canine distemper virus (CDV) are highly contagious canine pathogens; dogs with these diseases are difficult to treat. In a previous study, we developed a recombinant adenovirus expressing canine interferon lambda 3 (Ad-caIFNλ3) in canine epithelial cells. In this study, we aimed to investigate the antiviral activity of Ad-caIFNλ3 against CCoV, CPV, and CDV in two canine cell lines, A72 and MDCK. Ad-caIFNλ3 transduction suppressed replication of these viruses without cytotoxicity. Our results suggest that Ad-caIFNλ3 may be a therapeutic candidate for canine viral diseases.

Receptor-interacting protein kinase-3 （RIP3 or RIPK3） is an essential part of the cellular machinery that executes ＂programmed＂ or ＂regulated＂ necrosis. Here we show that programmed necrosis is activated in response to many chemotherapeutic agents and contributes to chemotherapy-induced cell death. However, we show that RIP3 expres- sion is often silenced in cancer cells due to genomic methylation near its transcriptional start site, thus RIP3-depen- dent activation of MLKL and downstream programmed necrosis during chemotherapeutic death is largely repressed. Nevertheless, treatment with hypomethylating agents restores RIP3 expression, and thereby promotes sensitivity to chemotherapeutics in a RIP3-dependent manner. RIP3 expression is reduced in tumors compared to normal tissue in 85% of breast cancer patients, suggesting that RIP3 deficiency is positively selected during tumor growth/develop- ment. Since hypomethylating agents are reasonably well-tolerated in patients, we propose that RIP3-deficient cancer patients may benefit from receiving hypomethylating agents to induce RIP3 expression prior to treatment with con- ventional chemotherapeutics.