Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea, November 2021.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.

Phenolic Compounds from the Leaves and Twigs of Osteomeles schwerinae That Inhibit Rat Lens Aldose Reductase and Vessel Dilation in Zebrafish Larvae.

Three new phenolic biphenyl derivatives (1-3) and one new lignan glycoside (4) were isolated from the leaves and twigs of Osteomeles schwerinae. The structures of the new compounds were established by spectroscopic data interpretation. The inhibitory effects of 1-4 on rat lens aldose reductase in vitro were examined, and compounds 1-3 markedly inhibited the enzyme with IC50 values of 3.8 to 13.8 µM. In addition, the effects of these isolates on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in zebrafish larvae were investigated. Compound 1 was the most effective in reducing HG-induced dilation of hyaloid-retinal vessels.

Effects of Allium victorialis leaf extracts and its single compounds on aldose reductase, advanced glycation end products and TGF-ß1 expression in mesangial cells.

BACKGROUND: Accumulating evidences suggest that aldose reductase (AR) inhibitors and advanced glycation end product (AGE) formation inhibitors may prevent chronic hyperglycemia-induced long-term complication in diabetes. Transforming growth factor-beta1 (TGF-ß1) plays an important role in the development of diabetic nephropathy. Allium species have been utilized in folk medicine throughout the world for the treatment of various physical disorders. However, the benefits of Allium victorialis (A. victorialis) against diabetic complications, especially nephropathy, have yet to be explored. In the present study, we investigated the protective effect of the compounds isolated from A. victorialis leaf on diabetic nephropathy. METHODS: In vitro AR activity, AGEs formation, and AGE-receptor for AGEs (RAGE) binding in human RAGE (hRAGE)-overexpressing cells were tested. High glucose-induced transforming growth factor-beta1 (TGF-ß1) expression was also examined in mouse kidney mesangial cells (MMCs) cultured under high glucose. RESULTS: Of the isolated eight compounds from A. victorialis leaf extracts tested, quercitrin exhibited the most pronounced inhibitory effects on AR activity (IC50 value of 0.17 µM) and AGEs formation (IC50 value of 4.20 µM). Furthermore, quercitrin disrupted AGE-RAGE binding in a concentration-dependent manner in hRAGE-overexpressing cells. Additionally, of the eight compounds tested, ferulic acid significantly reduced high glucose-induced TGF-ß1 expression and secretion in MMCs. CONCLUSIONS: Our results suggest that active compounds isolated from A. victorialis leaf exhibit inhibitory effects on AR activity in rat lenses and AGE formation. Further, ferulic acid reduces TGF-ß1 mRNA expression and secretion in MMCs under diabetic conditions. Thus, A. victorialis is a good candidate for the development of treatments for diabetic nephropathy.

Direct indicators of social distancing effectiveness in COVID-19 outbreak stages: a correlational analysis of case contacts and population mobility in Korea.

OBJECTIVES: The effectiveness of social distancing during the coronavirus disease 2019 (COVID-19) pandemic has been evaluated using the magnitude of changes in population mobility. This study aimed to investigate a direct indicator-namely, the number of close contacts per patient with confirmed COVID-19. METHODS: From week 7, 2020 to week 43, 2021, population movement changes were calculated from the data of two Korean telecommunication companies and Google in accordance with social distancing stringency levels. Data on confirmed cases and their close contacts among residents of Gyeonggi Province, Korea were combined at each stage. Pearson correlation analysis was conducted to compare the movement data with the change in the number of contacts for each confirmed case calculated by stratification according to age group. The reference value of the population movement data was set using the value before mid-February 2020, considering each data's characteristics. RESULTS: In the age group of 18 or younger, the number of close contacts per confirmed case decreased or increased when the stringency level was strengthened or relaxed, respectively. In adults, the correlation was relatively low, with no correlation between the change in the number of close contacts per confirmed case and the change in population movement after the commencement of vaccination for adults. CONCLUSIONS: The effectiveness of governmental social distancing policies against COVID-19 can be evaluated using the number of close contacts per confirmed case as a direct indicator, especially for each age group. Such an analysis can facilitate policy changes for specific groups.

Viral shedding patterns of symptomatic SARS-CoV-2 infections by periods of variant predominance and vaccination status in Gyeonggi Province, Korea.

OBJECTIVES: We compared the viral cycle threshold (Ct) values of infected patients to better understand viral kinetics by vaccination status during different periods of variant predominance in Gyeonggi Province, Korea. METHODS: We obtained case-specific data from the coronavirus disease 2019 (COVID-19) surveillance system, Gyeonggi in-depth epidemiological report system, and Health Insurance Review & Assessment Service from January 2020 to January 2022. We defined periods of variant predominance and explored Ct values by analyzing viral sequencing test results. Using a generalized additive model, we performed a nonlinear regression analysis to determine viral kinetics over time. RESULTS: Cases in the Delta variant's period of predominance had higher viral shedding patterns than cases in other periods. The temporal change of viral shedding did not vary by vaccination status in the Omicron-predominant period, but viral shedding decreased in patients who had completed their third vaccination in the Delta-predominant period. During the Delta-predominant and Omicron-predominant periods, the time from symptom onset to peak viral shedding based on the E gene was approximately 2.4 days (95% confidence interval [CI], 2.2 to 2.5) and 2.1 days (95% CI, 2.0 to 2.1), respectively. CONCLUSIONS: In one-time tests conducted to diagnose COVID-19 in a large population, although no adjustment for individual characteristics was conducted, it was confirmed that viral shedding differed by the predominant strain and vaccination history. These results show the value of utilizing hundreds of thousands of test data produced at COVID-19 screening test centers.

COVID-19 Outbreak in a Military Unit in Korea.

OBJECTIVES: This study presents the response of a military unit to the COVID-19 outbreak in Gyeonggi Province. As soon as two soldiers were identified as index cases, the infectious disease investigators of the Gyeonggi Provincial Government, Korea Disease Control and Prevention Agency and the Armed Forces Epidemiologic Investigation Center, discussed the investigation and response plan for an imminent massive outbreak. METHODS: The joint immediate response team (IRT) conducted interviews with confirmed patients with COVID-19, reviewed medical records, performed contact tracing using global positioning system (GPS), and undertook a field investigation. For risk assessment, the joint IRT visited all eight sites of the military units and the army chaplain's church to evaluate the transmission risk of each site. The evaluation items included the size of the site, the use of air conditioning, whether windows were opened, and whether masks were worn. A pooled testing was used for a low-risk population to quickly detect the spread of COVID-19 in the military base. RESULTS: A day before the symptom onset of the index case, the lecturer and >50% of the attendees were infected with COVID-19 while attending a lecture that lasted 2 h and 30 min. Attendees were not wearing masks and were in a poorly ventilated room. CONCLUSION: Since the disease can be spread before symptom onset, contact tracing must be performed to investigate potential exposures prior to symptom onset and manage any exposed persons.

Potentiation of T Cell Stimulatory Activity by Chemical Fixation of a Weak Peptide-MHC Complex.

The stability of peptide-MHC complex (pMHC) is an important factor to shape the fate of peptide-specific T cell immune response, but how it influences on T cell activation process is poorly understood. To better understand that, we investigated various T cell activation events driven by Ld MHCI loaded with graded concentrations of P2Ca and QL9 peptides, respectively, with 2C TCR Tg T cells; the binding strength of P2Ca for Ld is measurably weaker than that of QL9, but either peptides in the context of Ld interact with 2C TCR with a similar strength. When their concentrations required for early T cell activation events, which occur within several minutes to an hour, were concerned, EC50s of QL9 were about 100 folds lower than those of P2Ca, which was expected from their association constants for Ld. When EC50s for late activation events, which takes over several hours to occur, were concerned, the differences grew even larger (> 300 folds), suggesting that, due to weak binding, Ld/P2Ca dissociate from each other more easily to lose its antigenicity in a short time. Accordingly, fixation of Ld/P2Ca with paraformaldehyde resulted in a significant improvement in its immunogenicity. These results imply that binding strength of a peptide for a MHC is a critical factor to determine the duration of pMHC-mediated T cell activation and thus the attainment of productive T cell activation. It is also suggested that paraformaldehyde fixation should be an effective tool to ameliorate the immunogenicity of pMHC with a poor stability.

Myricetin inhibits advanced glycation end product (AGE)-induced migration of retinal pericytes through phosphorylation of ERK1/2, FAK-1, and paxillin in vitro and in vivo.

Advanced glycation end products (AGE) have been implicated in the development of diabetic retinopathy. Characterization of the early stages of diabetic retinopathy is retinal pericytes loss, which is the result of pericytes migration. In this study, we investigated the pathological mechanisms of AGE on the migration of retinal pericytes and confirmed the inhibitory effect of myricetin on migration in vitro and in vivo. Migration assays of bovine retinal pericytes (BRP) were induced using AGE-BSA and phosphorylation of Src, ERK1/2, focal adhesion kinase (FAK-1) and paxillin were determined using immunoblot analysis. Sprague-Dawley rats (6 weeks old) were injected intravitreally with AGE-BSA and morphological and immunohistochemical analysis of p-FAK-1 and p-paxillin were performed in the rat retina. Immunoblot analysis and siRNA transfection were used to study the molecular mechanism of myricetin on BRP migration. AGE-BSA increased BRP migration in a dose-dependent manner via receptor for AGEs (RAGE)-dependent activation of the Src kinase-ERK1/2 pathway. AGE-BSA-induced migration was inhibited by an ERK1/2 specific inhibitor (PD98059), but not by p38 and Jun N-terminal kinase inhibitors. AGE-BSA increased FAK-1 and paxillin phosphorylation in a dose- and time-dependent manner. These increases were attenuated by PD98059 and ERK1/2 siRNA. Phosphorylation of FAK-1 and paxillin was increased in response to AGE-BSA-induced migration of rat retinal pericytes. Myricetin strongly inhibited ERK1/2 phosphorylation and significantly suppressed pericytes migration in AGE-BSA-injected rats. Our results demonstrate that AGE-BSA participated in the pathophysiology of retinal pericytes migration likely through the RAGE-Src-ERK1/2-FAK-1-paxillin signaling pathway. Furthermore, myricetin suppressed phosphorylation of ERK 1/2-FAK-1-paxillin and inhibited pericytes migration.

Gas6 stimulates angiogenesis of human retinal endothelial cells and of zebrafish embryos via ERK1/2 signaling.

AIM: To determine if growth arrest-specific 6 (Gas6) plays an important role in the regulation of angiogenesis in human retinal microvascular endothelial cells (HRMECs) and in vessel development of zebrafish. METHODS: Proliferation, wound-healing cell migration, and tube formation were measured in HRMECs treated with recombinant human Gas6 (rhGas6). Sprague-Dawley rat aortas in Matrigels were treated with rhGas6, and microvessel sprouting emanating from arterial rings was analyzed. Transgenic zebrafish embryos (flk:GFP) were microinjected with rhGas6 at 50 hours post-fertilization (hpf), and ectopic sprouting of subintestinal vessels (SIVs) was observed under a confocal microscope. Morpholino oligonucleotides (MOs) were microinjected to knockdown gas6 in zebrafish embryos, and intersegmental vessel impairment was observed. The effect of the extracellular signal-regulated kinase (ERK1/2) inhibitor on the migration of HRMECs and on vessel development in zebrafish embryos was tested. RESULTS: rhGas6 stimulated proliferation, migration, and tube formation in HRMECs in a dose-dependent manner. In rat aortas, rhGas6 induced vessel outgrowth, and the sprouting length was longer than that of controls. The rhGas6-microinjected zebrafish embryos had significantly increased vessel outgrowth in the SIVs. Recombinant human vascular endothelial growth factor (rhVEGF) served as a positive control. Knockdown of gas6 inhibited angiogenesis in the developing vessels of zebrafish. The ERK1/2 inhibitor inhibited HRMEC migration and intersegmental vessel formation in zebrafish embryos. CONCLUSIONS/INTERPRETATIONS: These data suggest that Gas6 plays a pivotal role in proliferation, migration, and sprouting of angiogenic endothelial cells in the retina and in zebrafish embryos. Furthermore, Gas6 induced angiogenic processes are induced via phosphorylation of ERK1/2.