BPES (Blepharophimosis/Ptosis/Epicanthus inversus Syndrome) is an autosomal dominant disorder caused by mutations in FOXL2. Affected individuals have premature ovarian failure (POF) in addition to small palpebral fissures, drooping eyelids, and broad nasal bridge. FOXL2 is a member of the forkhead family transcription factors. In FOXL2-deficient ovaries, granulosa cell differentiation dose not progress, leading to arrest of folliculogenesis and oocytes atresia. Using yeast two-hybrid screening of rat ovarian cDNA library with FOXL2 as bait, we found that small ubiquitin-related modifier (SUMO)-conjugating E2 enzyme UBE2I protein interacted with FOXL2 protein. UBE2I also known as UBC9 is an essential protein for processing SUMO modification. Sumoylation is a form of post-translational modification involved in diverse signaling pathways including the regulation of transcriptional activities of many transcriptional factors. In the present study, we confirmed the protein-protein interaction between FOXL2 and UBE2I in human cells, 293T, by in vivo immunoprecipitation. In addition, we generated truncated FOXL2 mutants and identified the region of FOXL2 required for its association with UBE2I using yeast-two hybrid system. Therefore, the identification of UBE2I as an interacting protein of FOXL2 further suggests a presence of novel regulatory mechanism of FOXL2 by sumoylation.
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.
Hye Jeong Moon;Mi Seon Han;Kyung Min Kim;Kyung Jin Oh;Ju Young Chang;Seong Yong Lee;Ji Eun Choi
Pediatric Infection and Vaccine
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v.30
no.2
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pp.84-90
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2023
Purpose: Infants aged ≤90 days with fever are susceptible to severe infections. This study aimed to analyze the clinical features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in this particular age group. Methods: Infants aged ≤90 days who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized between March 1, 2020, and May 1, 2022 were included. Medical records of patients were retrospectively reviewed. Results: A total of 105 infants with COVID-19 were included; 27 (25.7%) neonates aged <28 days, and 48 (45.7%) and 30 (28.6%) infants aged 28-59 days and 60-90 days, respectively. Five (4.7%) patients remained asymptomatic and 68 (62.8%) were febrile, with a median fever duration of 2 days. The most common symptoms were respiratory including cough (66.6%), nasal stuffiness (51.4%), and rhinorrhea (40.9%). Blood cultures were performed in 10 infants but no organisms were detected. Cultures of bag-collected urine specimens from 8 infants were grown, resulting in positive growth for 2 without pyuria. Nine (8.6%) infants were treated with empirical antibiotics for a median duration of 2.3 days (range, 1-7 days). All 105 infants showed improvement without any complications, and there were no fatal cases. Conclusions: In this study, most infants aged ≤90 days with COVID-19 presented with mild symptoms and none of those evaluated had documented bacterial co-infection. The favorable prognosis among young infants with SARS-CoV-2 may aid clinicians in tailoring their approach to evaluation and management during outbreaks.
Concentration of nitrogen, one of the major elements, and ratio of two nitrogen forms (NH4+ and NO3-) in the nutrient solution affect the quality and food safety of fresh vegetable produce. This study was conducted to find an appropriate strength and NH4+:NO3- ratio of a nutrient solution for growth and development of a Romaine lettuce (Lactuca sativa L. var. longiflora) 'Caesar Green', a representative leafy vegetable, grown in a home hydroponic system. In the first experiment, plants were grown using three types of nutrient solution: A commercial nutrient solution (Peters) and two strengths (GNU1 and GNU2) of a multipurpose nutrient solution (GNU solution) developed in a Gyeongsang National University lab. Plants grown with the GNU1 and GNU2 had greater shoot length, leaf length and width, and biomass yield than Peters. On the other hand, the root hairs of plants grown with Peters were short and dark in color. Tissue NH4+ content in the Peters was higher than that of the GNU1 and GNU2. The higher contents of NH4+ in this solution may have caused ammonium toxicity. In the second experiment, eight treatment solutions, combining GNU1 and GNU2 solutions with four ratios of NO3- :NH4+ named as 1, 2, 3 and 4 were used. Both experiments showed more growth in the GNU2 group, which had a relatively low ionic strength of the nutrient solution. The growth of Romaine lettuce showed the greatest fresh weight along with low tissue NO3- content in the GNU2-2. This was more advantageous in terms of food safety in that it suppressed the accumulation of surplus NO3- in tissues due to the low ionic trength of the GNU2 subgroup. In addition, this is preferable in that it can reduce the absolute amount of the input of inorganic nutrients to the nutrient solution.
Guk Jin Lee;Hyunho Kim;Sung Shim Cho;Hyung Soon Park;Ho Jung An;In Sook Woo;Jae Ho Byun;Ji Hyung Hong;Yoon Ho Ko;Der Sheng Sun;Hye Sung Won;Jong Youl Jin;Ji Chan Park ;In-Ho Kim;Sang Young Roh;Byoung Yong Shim
Journal of Gastric Cancer
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v.23
no.2
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pp.315-327
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2023
Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Materials and Methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250-0.890; P=0.020). Conclusions: After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.
In recent years, television dramas have adopted an emerging approach of imagining a just society via fantasy. This study set out to examine by stages the patterns of social justice in I Hear Your Voice, Pinocchio, and While You Were Sleeping written by Park Hye-ryeon, who has been leading this trend. I Hear Your Voice shows why social justice is needed, as it is set against the backdrop of a society in which legal justice has collapsed. In this drama, the collapse of the legal justice system indicates that democratic society is falling apart at the roots. As a result, pain and suffering is propagated among the petit bourgeois, with social justice being demanded as an alternative to this problematic reality. The supernatural power of reading the thoughts of others is used to remind viewers of the value of truth and trust and raises the possibility of the existence of a true heart as an alternative from a social justice perspective. Set in a society in which media justice is distorted, Pinocchio makes an attempt at changing ideas about social justice. In this drama, the corrupt media justice covers up truth and becomes a parasite to power, creating victims that are falsely accused. In this situation, the Pinocchio Syndrome, which makes people hiccup when telling a lie, shows paradoxically that truth can be distorted, and ultimately destroys absoluteness that is not truth. Finally, While You Were Sleeping inherits the world views of the two previous dramas and proposes a type of social justice called 'common good' as an alternative. A completely unfair society is created when legal justice collapses and media justice is distorted. In this situation, the ability to see the future is an ability to imagine a world of possibilities. Altruistic choices based on trust in others help us to realize a positive future. Social justice as common good to enable solidarity among subjects in a way that transcends the limitations of time and space is proposed as an alternative to overcome the problem of an unfair society. Given the recent reality of South Korean society, this common good and these ways of life might literally seem like a fantasy. When social justice is represented by efforts and reconstruction processes to overcome the current social issues and make a better future, common good based on the understanding and sympathy of others can be an alternative to improve a reality that is problematic at its root. Ultimately, Park's three works explore the feasibility of a just society that is yet to come from the aspect of the common good.
Doo Ri Kim;Kyung-Ran Kim;Hwanhee Park;Joon-sik Choi;Yoonsun Yoon;Sohee Son;Hee Young Ju;Jihyun Kim;Keon Hee Yoo;Kangmo Ahn;Hee-Jin Kim;Eun-Suk Kang;Junhun Cho;Su Eun Park;Kihyun Kim;Yae-Jean Kim
Pediatric Infection and Vaccine
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v.30
no.3
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pp.129-138
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2023
Purpose: Cancer incidence is known to be higher in patients with inborn errors of immunity (IEI) compared to the general population in addition to traditionally well-known infection susceptibility. We aimed to investigate cancer occurrence in patients with IEI in a single center. Methods: Medical records of IEI patients treated at Samsung Medical Center, Seoul, Korea were retrospectively reviewed from November 1994 to September 2023. Patients with IEI and cancer were identified. Results: Among 194 patients with IEI, seven patients (3.6%) were diagnosed with cancer. Five cases were lymphomas, 4 of which were Epstein-Barr virus (EBV)-associated lymphomas. The remaining cases included gastric cancer and multiple myeloma. The median age at cancer diagnosis was 18 years (range, 1-75 years). Among patients with cancer, underlying IEIs included X-linked lymphoproliferative disease-1 (XLP-1, n=3), activated phosphoinositide 3-kinase delta syndrome (APDS, n=2), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) haploinsufficiency (n=2). Seventy-five percent (3/4) of XLP-1 patients, 40.0% (2/5) of APDS patients, and 50.0% (2/4) of CTLA-4 haplo-insufficiency patients developed cancer. Patients with XLP-1 developed cancer at earlier age (median age 5 years) compared to those with APDS and CTLA-4 (P<0.001). One patient with APDS died during hematopoietic cell transplantation. Conclusions: Cancer occurred in 3.6% of IEI patients at a single center in Korea. In addition to infectious complications and inflammation, physicians caring for IEI patients should be aware of the potential risk of cancer, especially in association with EBV infection.
Jung Ah Kim;Sung-Hee Kim;Jeong Jin Kim;Hyuna Noh;Su-bin Lee;Haengdueng Jeong;Jiseon Kim;Donghun Jeon;Jung Seon Seo;Dain On;Suhyeon Yoon;Sang Gyu Lee;Youn Woo Lee;Hui Jeong Jang;In Ho Park;Jooyeon Oh;Sang-Hyuk Seok;Yu Jin Lee;Seung-Min Hong;Se-Hee An;Joon-Yong Bae;Jung-ah Choi;Seo Yeon Kim;Young Been Kim;Ji-Yeon Hwang;Hyo-Jung Lee;Hong Bin Kim;Dae Gwin Jeong;Daesub Song;Manki Song;Man-Seong Park;Kang-Seuk Choi;Jun Won Park;Jun-Won Yun;Jeon-Soo Shin;Ho-Young Lee;Ho-Keun Kwon;Jun-Young Seo;Ki Taek Nam;Heon Yung Gee;Je Kyung Seong
IMMUNE NETWORK
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v.24
no.2
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pp.7.1-7.19
/
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.
Soo-Han Choi;Su-Yeon Yu;Jimin Kim;Miyoung Choi;Youn Young Choi;Jae Hong Choi;Ki Wook Yun;Young June Choe
Pediatric Infection and Vaccine
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v.31
no.1
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pp.12-24
/
2024
The number of pediatric coronavirus disease 2019 (COVID-19) cases worldwide are increasing compared to the early phase of the pandemic, along with highly transmissible severe acute respiratory syndrome coronavirus variant and the increase in adult COVID-19 vaccination. We conducted a rapid systematic review and meta-analysis of published randomized clinical trials (RCTs) of the COVID-19 vaccines and the observational retrospective studies on adverse events after COVID-19 vaccination in adolescents. Seventeen studies were finally included in this systematic review. Meta-analysis showed that although vaccination in adolescents was significantly effective to prevent COVID-19 infection in retrospective studies (risk ratio [RR], 0.29; 95% confidence interval [CI], 0.22-0.37; I2 =100%), however the effect of preventing COVID-19 infection was lower than in RCTs (RR, 0.05; 95% CI, 0.01-0.27). In five retrospective studies, the pooled estimated proportion of participants with myocarditis and/or pericarditis was 2.33 per 100,000 of the population (95% CI, 0.97-5.61 per 100,000). Sub-group analysis with sex and vaccine doses showed that male (5.35 per 100,000) and the second dose (9.71 per 100,000) had significantly higher incidence of myocarditis and/or pericarditis than female (1.09 per 100,000) and the first dose (1.61 per 100,000), respectively. Our study showed that mRNA COVID-19 vaccines in adolescent recipients were favorable and effective against COVID-19 in RCT as well as observational studies. The safety findings of BNT162b2 vaccine in adolescents were explored and we found the difference of safety according to sex and vaccine doses. The occurrence of adverse events after mRNA COVID-19 vaccination should be monitored.
The long-term results of combined mitral valve repair and aortic valve replacement (AVR) have not been well evaluated. This study was performed to investigate the early and long-term results of mitral valve repair with AVR. Material and Method: We retrospectively reviewed 45 patients who underwent mitral valve repair and AVR between September 1990 and April 2002. The average age was 47 years: 28 were men and 17 women. Twelve patients had atrial fibrillation and three had a previous cardiac operation. The mitral valve disease consisted of pure insufficiency (MR) in 34 patients, mitral stenosis (MS) in 3, and mixed lesion in 8. Mitral valve disease was due to rheumatic origin in 24 patients, degenerative in 11, annular dilatation in 8, and ischemia or endocarditis in 2. The functional anatomy of mitral valve was annular dilatation in 31 patients, chordal elongation in 19, leaflet thickening in 19, commissural fusion in 13, chordal fusion in 10, chordal rupture in 6, and so on. Aortic prostheses used included mechanical valve in 32 patients, tissue valve in 12, and pulmonary autograft in one. The techniques of mitral valve repair included annuloplasty in 32 patients and various valvuloplasty of 54 techniques in 29 patients. Total cardiopulmonary bypass and aortic cross clamp time were 204$\pm$62 minute and 153$\pm$57 minutes, respectively. Result: Early death was in one patient due to low output syndrome (2.2%). After follow up of 57$\pm$37 months, late death was in one patient and the actuarial survival at 10 years was 96$\pm$4%. Recurrent MR developed grade II or III in 11 patients and moderate MS in 3. Three patients required reoperation for valve-related complications. The actuarial freedom from recurrent MR, MS, and reoperation were 64$\pm$11%, 86$\pm$8%, and 89$\pm$7% respectively. Conclusion: Combined mitral valve repair with AVR offers good early and long-term survival, and adequate techniques and selection of indication of mitral valve repair, especially in rheumatic disease, are prerequisites for better long-term results.
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