1.Complement C5a Receptor Signalingin Macrophages Enhances Trained Immunity Through mTOR Pathway Activation
Eun-Hyeon SHIM ; Sae-Hae KIM ; Doo-Jin KIM ; Yong-Suk JANG
Immune Network 2024;24(4):e24-
Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.
2.Complement C5a Receptor Signalingin Macrophages Enhances Trained Immunity Through mTOR Pathway Activation
Eun-Hyeon SHIM ; Sae-Hae KIM ; Doo-Jin KIM ; Yong-Suk JANG
Immune Network 2024;24(4):e24-
Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.
3.Complement C5a Receptor Signalingin Macrophages Enhances Trained Immunity Through mTOR Pathway Activation
Eun-Hyeon SHIM ; Sae-Hae KIM ; Doo-Jin KIM ; Yong-Suk JANG
Immune Network 2024;24(4):e24-
Complement C5a receptor (C5aR) signaling in immune cells has various functions, inducing inflammatory or anti-inflammatory responses based on the type of ligand present. The Co1 peptide (SFHQLPARSRPLP) has been reported to activate C5aR signaling in dendritic cells. We investigated the effect of C5aR signaling via the Co1 peptide on macrophages. In peritoneal macrophages, the interaction between C5aR and the Co1 peptide activated the mTOR pathway, resulting in the production of pro-inflammatory cytokines. Considering the close associations of mTOR signaling with IL-6 and TNF-α in macrophage training, our findings indicate that the Co1 peptide amplifies β-glucan-induced trained immunity. Overall, this research highlights a previously underappreciated aspect of C5aR signaling in trained immunity, and posits that the Co1 peptide is a potentially effective immunomodulator for enhancing trained immunity.
4.Practice guidelines for managing extrahepatic biliary tract cancers
Hyung Sun KIM ; Mee Joo KANG ; Jingu KANG ; Kyubo KIM ; Bohyun KIM ; Seong-Hun KIM ; Soo Jin KIM ; Yong-Il KIM ; Joo Young KIM ; Jin Sil KIM ; Haeryoung KIM ; Hyo Jung KIM ; Ji Hae NAHM ; Won Suk PARK ; Eunkyu PARK ; Joo Kyung PARK ; Jin Myung PARK ; Byeong Jun SONG ; Yong Chan SHIN ; Keun Soo AHN ; Sang Myung WOO ; Jeong Il YU ; Changhoon YOO ; Kyoungbun LEE ; Dong Ho LEE ; Myung Ah LEE ; Seung Eun LEE ; Ik Jae LEE ; Huisong LEE ; Jung Ho IM ; Kee-Taek JANG ; Hye Young JANG ; Sun-Young JUN ; Hong Jae CHON ; Min Kyu JUNG ; Yong Eun CHUNG ; Jae Uk CHONG ; Eunae CHO ; Eui Kyu CHIE ; Sae Byeol CHOI ; Seo-Yeon CHOI ; Seong Ji CHOI ; Joon Young CHOI ; Hye-Jeong CHOI ; Seung-Mo HONG ; Ji Hyung HONG ; Tae Ho HONG ; Shin Hye HWANG ; In Gyu HWANG ; Joon Seong PARK
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(2):161-202
Background:
s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021.
Methods:
Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop.
Results:
In November 2021, the finalized draft was presented for public scrutiny during a formal hearing.
Conclusions
The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.
5.Factors Associated with Reaching Mid-Parental Height in Patients Diagnosed with Inflammatory Bowel Disease in Childhood and Adolescent Period
So Yoon CHOI ; Sujin CHOI ; Byung-Ho CHOE ; Jae Hong PARK ; Kwang-Hae CHOI ; Hae Jeong LEE ; Ji Sook PARK ; Ji-Hyun SEO ; Jae Young KIM ; Hyo-Jeong JANG ; Suk Jin HONG ; Eun Young KIM ; Yeoun Joo LEE ; Ben KANG
Gut and Liver 2024;18(1):106-115
Background/Aims:
The recent update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added normal growth in children as an intermediate target in Crohn’s disease and ulcerative colitis. We aimed to investigate factors associated with reaching midparental height (MPH) in patients diagnosed with inflammatory bowel disease in childhood and the adolescent period.
Methods:
This multicenter retrospective observational study included pediatric patients with inflammatory bowel disease that had reached adult height. Factors associated with reaching MPH were investigated by logistic regression analyses.
Results:
A total of 166 patients were included in this study (128 Crohn’s disease and 38 ulcerative colitis). Among them, 54.2% (90/166) had reached their MPH. Multivariable logistic regression analysis revealed that height Z-score at diagnosis and MPH Z-score were independently associated with reaching MPH (odds ratio [OR], 8.45; 95% confidence interval [CI], 4.44 to 17.90;p<0.001 and OR, 0.11; 95% CI, 0.04 to 0.24; p<0.001, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level of "height Z-score at diagnosis minus MPH Z-score" that was associated with reaching MPH was –0.01 with an area under the curve of 0.889 (95% CI [0.835 to 0.944], sensitivity 88.9%, specificity 84.2%, positive predictive value 87.0%, negative predictive value 86.5%, p<0.001).
Conclusions
Height Z-score at diagnosis and MPH Z-score were the only factors associated with reaching MPH. Efforts should be made to restore growth in pediatric patients who present with a negative “height Z-score at diagnosis minus MPH Z-score.”
6.Development of Mental Healthcare Model in Seoul
Sra JUNG ; Soo Bong JUNG ; Eun Jin NA ; Jee Hye BAE ; Jong Woo PAIK ; Hwo Yeon SEO ; Jee Hoon SOHN ; Hae Woo LEE ; Jeung Suk LIM ; Mi JANG ; Sung Joon CHO ; Hwa Young LEE
Psychiatry Investigation 2023;20(7):655-663
Objective:
To develop an integrated and comprehensive community-based mental healthcare model, opinions were collected on various issues from practitioners in mental health service institutions currently offering mental healthcare services in Seoul through a focus group interview, qualitative research method, and Delphi survey.
Methods:
The focus group interview was conducted with six practitioners from mental health welfare centers and six hospital-based psychiatrists. A questionnaire of opinions on the mental healthcare model was filled by these practitioners and psychiatrists. A Delphi survey was additionally conducted with a panel of 20 experts from a community mental health welfare center and hospital-based psychiatrists.
Results:
The focus group interview results showed the need for integrated community-based mental healthcare service and the need to establish a system for managing mental and physical health in an integrated manner. Based on the survey results, the current status of community-based mental healthcare services was investigated, and the direction of the revised model was established. The Delphi survey was then conducted to refine the revised model.
Conclusion
The present study presents the Seoul-type community-based mental healthcare model with integrated services between a psychiatric hospital with a mental health welfare center as well as combined mental and physical health services. This is ultimately expected to help people with mental illnesses live healthy lives by meeting their needs as community members.
7.Clinical Characteristics and Risk Factors for Mortality in Critical Coronavirus Disease 2019 Patients 50 Years of Age or Younger During the Delta Wave: Comparison With Patients > 50 Years in Korea
Hye Jin SHI ; Eliel NHAM ; Bomi KIM ; Eun-Jeong JOO ; Hae Suk CHEONG ; Shin Hee HONG ; Miri HYUN ; Hyun ah KIM ; Sukbin JANG ; Ji-Young RHEE ; Jungok KIM ; Sungmin KIM ; Hyun Kyu CHO ; Yu Mi WI ; Shinhye CHEON ; Yeon-Sook KIM ; Seungjin LIM ; Hyeri SEOK ; Sook In JUNG ; Joong Sik EOM ; Kyong Ran PECK
Journal of Korean Medical Science 2022;37(22):e175-
Background:
Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea.
Methods:
We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics.
Results:
During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m 2 .Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092;95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients.Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group.The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m 2 ), and the one remaining patient died from a secondary infection.
Conclusion
About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m2 ) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.
8.Management of Osteoporotic Vertebral Fracture: Review Update 2022
Hae-Dong JANG ; Eung-Ha KIM ; Jae Chul LEE ; Sung-Woo CHOI ; Hak Soo KIM ; Joong-Suk CHA ; Byung-Joon SHIN
Asian Spine Journal 2022;16(6):934-946
A vertebral fracture is the most common type of osteoporotic fracture. Osteoporotic vertebral fractures (OVFs) cause a variety of morbidities and deaths. There are currently few “gold standard treatments” outlined for the management of OVFs in terms of quantity and quality. Conservative treatment is the primary treatment option for OVFs. The treatment of pain includes short-term bed rest, analgesic medication, anti-osteoporotic medications, exercise, and a brace. Numerous reports have been made on studies for vertebral augmentation (VA), including vertebroplasty and kyphoplasty. There is still debate and controversy about the effectiveness of VA in comparison with conservative treatment. Until more robust data are available, current evidence does not support the routine use of VA for OVF. Despite the fact that the majority of OVFs heal without surgery, 15%–35% of patients with an unstable fracture, persistent intractable back pain, or severely collapsed vertebra that causes a neurologic deficit, kyphosis, or chronic pseudarthrosis frequently require surgery. Because no single approach can guarantee the best surgical outcomes, customized surgical techniques are required. Surgeons must stay current on developments in the osteoporotic spine field and be open to new treatment options. Osteoporosis management and prevention are critical to lowering the risk of future OVFs. Clinical studies on bisphosphonate’s effects on fracture healing are lacking. Teriparatide was intermittently administered, which dramatically improved spinal fusion and fracture healing while lowering mortality risk. According to the available literature, there are no standard management methods for OVFs. More multimodal approaches, including conservative and surgical treatment, VA, and medications that treat osteoporosis and promote fracture healing, are required to improve the quality of the majority of guidelines.
9.Severe Disease Activity Based on the Paris Classification Is Associated with the Development of Extraintestinal Manifestations in Korean Children and Adolescents with Ulcerative Colitis
Hyo-Jeong JANG ; Hyo Rim SUH ; Sujin CHOI ; Suk Jin HONG ; Seung-Man CHO ; Kwang-Hae CHOI ; Byung-Ho CHOE ; Ben KANG ;
Journal of Korean Medical Science 2021;36(44):e278-
Background:
There are limited data regarding the extraintestinal manifestations (EIMs) associated with pediatric inflammatory bowel disease (IBD) in Korea. We aimed to investigate the clinical features and factors associated with the development of EIMs in Korean children and adolescents with IBD.
Methods:
This multicenter, retrospective study was conducted from 2010 to 2017. Baseline clinicodemographic, laboratory findings, disease activity, disease phenotypes, and EIMs were investigated.
Results:
A total of 172 patients were included. One-hundred thirty-seven (79.7%) had Crohn's disease (CD), and 35 (20.3%) had ulcerative colitis (UC). EIMs occurred in 42 patients (24.4%). EIMs developed in 34/137 diagnosed with CD (24.8%), and in 8/35 diagnosed with UC (22.9%), during a median follow-up duration of 3.2 (interquartile range, 1.9–5.4) years for CD and 3.0 (1.0–4.0) years for UC, respectively. Arthritis/arthralgia was most commonly observed (n = 15, 35.7%), followed by stomatitis/oral ulcer (n = 10, 23.8%), hepatitis (n = 5, 11.9%), nephritis (n = 4, 9.5%), pancreatitis (n = 2, 4.8%), erythema nodosum (n = 2, 4.8%), pyoderma gangrenosum (n = 1, 2.4%), primary sclerosing cholangitis (n = 1, 2.4%), uveitis (n = 1, 2.4%), and ankylosing spondylitis (n = 1, 2.4%). A significant difference in disease severity based on the Paris classification (P = 0.011) and ESR at diagnosis (P = 0.043) was observed between the EIM positive and negative group in patients with UC. According to logistic regression analyses, S1 disease severity based on the Paris classification was the only factor that was significantly associated with the development of EIMs (odds ratio, 16.57; 95% confidence interval, 2.18–287.39; P = 0.017).
Conclusion
Severe disease activity based on the Paris classification in pediatric patients with UC was significantly associated with EIM development. As disease severity in the Paris classification is a dynamic parameter, treatment should be focused on disease control to minimize the occurrence of EIMs in Korean children and adolescents with UC.
10.Recent Insights into Cellular Crosstalk in Respiratory and Gastrointestinal Mucosal Immune Systems
Immune Network 2020;20(6):e44-
The human body is continuously threatened by pathogens, and the immune system must maintain a balance between fighting infection and becoming over-activated. Mucosal surfaces cover several anatomically diverse organs throughout the body, such as the respiratory and gastrointestinal tracts, and are directly exposed to the external environment.Various pathogens invade the body through mucosal surfaces, making the mucosa the frontline of immune defense. The immune systems of various mucosal tissues display distinctive features that reflect the tissues' anatomical and functional characteristics. This review discusses the cellular components that constitute the respiratory and gastrointestinal tracts; in particular, it highlights the complex interactions between epithelial and immune cells to induce Ag-specific immune responses in the lung and gut. This information on mucosal immunity may facilitate understanding of the defense mechanisms against infectious agents that invade mucosal surfaces, such as severe acute respiratory syndrome coronavirus 2, and provide insight into effective vaccine development.

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