No abstract

Summary Background Dermal papilla cells (DPCs) play a key role in hair regeneration and morphogenesis. Therefore, tremendous efforts have been made to promote DPC hair inductivity. Objectives The aim of this study was to investigate the mitogenic and hair inductive effects of hypoxia on DPCs and examine the underlying mechanism of hypoxia‐induced stimulation of DPCs. Methods DPCs' hair inductivity was examined under normoxia (20% O2) and hypoxia (2% O2). Results Hypoxia significantly increased the proliferation and delayed senescence of DPCs via Akt phosphorylation and downstream pathways. Hypoxia upregulated growth factor secretion of DPCs through the mitogen‐activated protein kinase pathway. Hypoxia‐preconditioned DPCs induced the telogen‐to‐anagen transition in C3H mice, and also enhanced hair neogenesis in a hair reconstitution assay. Injected green fluorescent protein‐labelled DPCs migrated to the outer root sheath of the hair follicle, and hypoxia‐preconditioning increased survival and migration of DPCs in vivo. Conditioned medium obtained from hypoxia increased the hair length of mouse vibrissa follicles via upregulation of alkaline phosphatase, vascular endothelial growth factor, and glial cell line‐derived neurotrophic factor. We examined the mechanism of this hypoxia‐induced stimulation, and found that reactive oxygen species (ROS) play a key role. For example, inhibition of ROS generation by N‐acetylcysteine or diphenyleneiodonium treatment attenuated DPCs' hypoxia‐induced stimulation, but treatment with ROS donors induced mitogenic effects and anagen transition. NADPH oxidase 4 is highly expressed in the DPC nuclear region, and NOX4 knockout by CRISPR‐Cas9 attenuated the hypoxia‐induced stimulation of DPCs. Conclusions Our results suggest that DPC culture under hypoxia has great advantages over normoxia, and is a novel solution for producing DPCs for cell therapy. Whatʼs already known about this topic? Dermal papilla cells (DPCs) play a key role in hair regeneration and morphogenesis, but they are difficult to isolate and expand for use in cell therapy. Tremendous efforts have been made to increase proliferation of DPCs and promote their hair formation ability. What does this study add? Hypoxia (2% O2) culture of DPCs increases proliferation, delays senescence and enhances hair inductivity of DPCs. Reactive oxygen species play a key role in hypoxia‐induced stimulation of DPC. What is the translational message? Preconditioning DPCs under hypoxia improves their hair regenerative potential, and is a novel solution for producing DPCs for cell therapy to treat hair loss.

Background Complete contact tracing of COVID-19 patients in Korea allows a unique opportunity to investigate cluster characteristics. This study aimed to investigate all the reported COVID-19 clusters in Seoul Metropolitan area from January 23 to September 24, 2020. Methods Publicly available COVID-19 data was collected from the Seoul Metropolitan city and Gyeonggi Province. Community clusters with ≥ 5 cases were characterized by size and duration and then categorized using K-means clustering, and the correlation between the types of clusters and the level of social distancing was investigated. Results A total of 134 clusters including 4,033 cases were identified. The clusters were categorized into small (Type I, II), medium (type III), and large (type IV) clusters. With the same number of daily confirmed cases, cases were composed of different types of clusters by different periods of time. Raising social distancing was related with shifting types of clusters from large to small sized clusters. Conclusions Classification of clusters may provide opportunities to better portray the pattern of COVID-19 outbreaks and implement more effective strategies. Social distancing administered by the government may be effective in suppressing large clusters but may not be effective in controlling small and sporadic clusters.

0.05) during the 35-d period decreased linearly as CSB supplementation levels increased in the diets. In conclusion, CSB supplementation tended to increase colostral IgG and IgA concentrations in sows and improved growth performance of nursery pigs under an immune challenge when supplemented in the nursery diet.

Interleukin (IL)-22 is a potent mediator of inflammatory responses. The IL-22 receptor consists of the IL-22Rα and IL-10Rβ subunits. Previous studies have shown that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung, and kidney. Although IL-22 is involved in the development of inflammatory responses, there have been no reports of its role in brain inflammation. Here, we used RT-PCR, Western blotting, flow cytometry, immunohistochemical, and microarray analyses to examine the role of IL-22 and expression of IL-22Rα in the brain, using the microglial cell line, hippocampal neuronal cell line, and inflamed mouse brain tissue. Treatment of BV2 and HT22 cells with recombinant IL-22 increased the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α, as well as cyclooxygenase (COX)-2 and prostaglandin E2. We also found that the JNK and STAT3 signaling pathways play an important role in IL-22-mediated increases in inflammatory mediators. Microarray analyses revealed upregulated expression of inflammation-related genes in IL-22-treated HT22 cells. Finally, we found that IL-22Rα is spontaneously expressed in the brain and is upregulated in inflamed mouse brain. Overall, our results demonstrate that interaction of IL-22 with IL-22Rα plays a role in the development of inflammatory responses in the brain.

Background: Mycoplasma pneumoniae pneumonia (MP) is a major cause of community acquired pneumonia (CAP) in children and it is known to be associated with extrapulmonary manifestations (EPM). The incidence and risk factors of EPM in children are not known.Methods: This is a retrospective study involving 65,243 pediatric CAP patients between 2010 and 2015 at 23 nationwide hospitals was conducted in South Korea. The medical records were reviewed to collect the information regarding the clinical characteristics, radiological results, and laboratory findings. In total, 9,190 children with MP were identified and included in the analysis. Logistic regression with multivariable analysis was performed to evaluate the risk factors associated with EPM in MP.Results: The mean age of the enrolled patients with MP was 64.3±39.8 months, and the proportion of male patients was 49.5%. The incidence of EPM was 23.9% and included elevation of liver enzymes (18.1%), mucocutaneous manifestations (4.4%), proteinuria (4.1%), cardiovascular and neurologic manifestation (0.4%), hematologic manifestation (0.2%) and arthritis (0.2%). Statistical analysis showed that mucocutaneous manifestations were significantly increased with elevated alanine aminotransferase (adjusted odds ratio [aOR] 3.623, 95% confidence intervals [CI] 1.933-6.790) and atopic sensitization (aOR 2.973, 95% CI 1.615-5.475) and decreased with respiratory virus co-infection (aOR 0.273, 95% CI 0.084-0.887). Elevated liver enzymes was significantly associated with the elevation of lactate dehydrogenase (aOR 3.055, 95% CI 2.257-4.137) and presence of pleural effusion (aOR 2.635, 95% CI 1.767-3.930) and proteinuria with respiratory virus co-infection (aOR 2.245, 95% CI 1.113-4.527). Conclusions: About 24% of pediatric MP patients were identified with various EPM. Since risk factors associated with each EPM was different, it is necessary to evaluate the various clinical aspects and findings of MP to predict and prepare for the occurrence of EPM.

Objectives: During the coronavirus disease (COVID-19) pandemic, crude incidence and mortality rates have been widely reported; however, age-standardized rates are more suitable for comparison. In this study, we estimated and compared the age-standardized incidence, mortality, and case fatality rates among countries and investigated the relationship between these rates and factors associated with healthcare resources: gross domestic product per capita, number of hospital beds per population, and number of doctors per population. Methods:The incidence, mortality, and case fatality rates of 79 countries were age-standardized using the WHO standard population. The rates for persons 60 years or older were also calculated. The relationships among the rates were analysed using trend lines and coefficients of determination (R 2 ). The Pearson's correlation coefficients between the rates and the healthcare resource-related factors were calculated. Results:The countries with the highest age-standardized incidence, mortality, and case fatality rates were Czechia (14,253 cases/100,000), Mexico (182 deaths/100,000), and Mexico (6.7%), respectively. The R 2 between the incidence and mortality rates was 0.8520 for all ages and 0.9452 for those 60 years or older. The healthcare resources-related factors were associated positively with incidence rates, and negatively with case fatality rates: the correlations were weaker among the elderly.Conclusions: Compared to age-standardized rates, crude rates showed greater variation between countries. Medical resources may be important in preventing COVID-19-related deaths; however, considering the small variation in fatality among the elderly, prevention such as vaccination is more important especially for the elderly population to minimize the mortality rates in the elderly population.

Although several studies have evaluated the association between fine particulate matter (PM2.5) and acute lower respiratory infection (ALRI) in children, their results were inconsistent Therefore, we aimed to evaluate the association between short-term exposure to PM2.5 and ALRI hospitalizations in children (0–5 years) living in seven metropolitan cities of Korea. The ALRI hospitalization data of children living in seven metropolitan cities of Korea from 2008 to 2016 was acquired from a customized database constructed based on National Health Insurance data. The time-series data in a generalized additive model were used to evaluate the relationship between ALRI hospitalization and 7-day moving average PM2.5 exposure after adjusting for apparent temperature, day of the week, and time trends. We performed a meta-analysis using a two-stage design method. The estimates for each city were pooled to generate an average estimate of the associations. The average PM2.5 concentration in 7 metropolitan cities was 29.0 μg/m3 and a total of 713,588 ALRI hospitalizations were observed during the 9-year study period. A strong linear association was observed between PM2.5 and ALRI hospitalization. A 10 μg/m3 increase in the 7-day moving average of PM2.5 was associated with a 1.20% (95% CI: 0.71, 1.71) increase in ALRI hospitalization. While we found similar estimates in a stratified analysis by sex, we observed stronger estimates of the association in the warm season (1.71%, 95% CI: 0.94, 2.48) compared to the cold season (0.31%, 95% CI: −0.51, 1.13). In the two-pollutant models, the PM2.5 effect adjusted by SO2 was attenuated more than in the single pollutant model. Our results suggest a positive association between PM2.5 exposure and ALRI hospitalizations in Korean children, particularly in the warm season. The children need to refrain from going out on days when PM2.5 is high.