1.Astragaloside IV regulates Snail1 lactylation and acetylation to mediate macrophage polarization and improve myocardial infarction.
Shaopeng CHEN ; Rudian KANG ; Xinbao HONG ; Yilong LIU
Chinese Journal of Cellular and Molecular Immunology 2025;41(4):289-299
Objective To investigate the impact of Astragaloside-IV (AS-IV) on the progression of myocardial infarction (MI) through macrophage-dependent mechanisms by regulating Snail1 lactylation and acetylation, as well as the transforming growth factor β (TGF-β) pathway. Methods Oxygen glucose deprivation (OGD) was used to establish an in vitro myocardial ischemia model in rat cardiomyocytes (H9c2), which were then treated with AS-IV. Cell viability was assessed using CCK-8, apoptosis was evaluated by flow cytometry, and LDH levels were measured to assess cellular damage. RAW246.7 cells were treated with LPS, and lactate levels in the supernatant were measured using ELISA, while expression of macrophage phenotype markers was evaluated using Western blot. RAW246.7 cell-conditioned medium (CM) was co-cultured with H9c2 cells to assess the protective effects of AS-IV on macrophage CM-mediated H9c2 damage. RAW246.7 cells were induced to differentiate into M1-like macrophages using LPS (100 ng/mL) + IFN-γ (20 ng/mL), and Snail1 was overexpressed in M1 macrophages. Transfected M1 macrophage CM was co-cultured with H9c2 cells to validate the mechanisms of AS-IV in MI. An MI rat model was established by ligation of the left anterior descending coronary artery (LAD), and was treated with AS-IV. Cardiac function, myocardial cell apoptosis, and cardiac tissue pathology were studied using echocardiography, TUNEL, and HE staining, respectively. Results Compared to the OGD group, AS-IV treatment promoted cell viability, reduced apoptosis and decreased LDH release. LPS upregulated lactate levels in the supernatant of RAW246.7 cell cultures and induced polarization of RAW246.7 cells to the M1 phenotype. AS-IV attenuated the damaging effects of RAW246.7 cell CM on H9c2 cells . Overexpression of Snail1 in M1 macrophages weakened the protective effects of AS-IV on H9c2 cells . In vivo study, results showed that, compared to the MI group, AS-IV treatment reduced lactate levels in the hearts of MI rats, improved cardiac function and myocardial injury and attenuated myocardial cell apoptosis. Conclusion AS-IV inhibits TGF-β pathway activation through the suppression of Snail1 lactylation and acetylation in a macrophage-dependent manner, thereby mitigating myocardial cell damage following MI.
Animals
;
Myocardial Infarction/drug therapy*
;
Rats
;
Snail Family Transcription Factors/metabolism*
;
Macrophages/cytology*
;
Myocytes, Cardiac/metabolism*
;
Triterpenes/pharmacology*
;
Saponins/pharmacology*
;
Acetylation/drug effects*
;
Apoptosis/drug effects*
;
Mice
;
Cell Line
;
RAW 264.7 Cells
;
Transforming Growth Factor beta/metabolism*
2.Prediction of Cancer Incidence and Mortality in Korea, 2024
Kyu-Won JUNG ; Mee Joo KANG ; Eun Hye PARK ; E Hwa YUN ; Hye-Jin KIM ; Jeong-Eun KIM ; Hyun-Joo KONG ; Jeong-Soo IM ; Hong Gwan SEO
Cancer Research and Treatment 2024;56(2):372-379
Purpose:
This study aimed to report the projected cancer incidence and mortality for the year 2024 to estimate Korea’s current cancer burden.
Materials and Methods:
Cancer incidence data from 1999 to 2021 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2022 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and multiplying the projected age-specific rates by the anticipated age-specific population for 2024. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend for prediction.
Results:
In total, 292,221 new cancer cases and 83,770 cancer deaths are expected to occur in Korea in 2024. The most common cancer site is expected to be the thyroid, followed by the colon and rectum, lung, breast, and stomach. These five cancers are expected to represent 55.7% of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and stomach cancers.
Conclusion
The age-standardized incidence rates for female breast and prostate cancers are estimated to continue to increase. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.
3.Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2021
Eun Hye PARK ; Kyu-Won JUNG ; Nam Ju PARK ; Mee Joo KANG ; E Hwa YUN ; Hye-Jin KIM ; Jeong-Eun KIM ; Hyun-Joo KONG ; Jeong-Soo IM ; Hong Gwan SEO ;
Cancer Research and Treatment 2024;56(2):357-371
Purpose:
The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2021.
Materials and Methods:
Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2021, with survival follow-up until December 31, 2022. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea.
Results:
The number of new cancer diagnoses in 2021 increased by 27,002 cases (10.8%) compared to 2020. In 2021, newly diagnosed cancer cases and deaths from cancer were reported as 277,523 (age-standardized rate [ASR], 289.3 per 100,000) and 82,688 (ASR, 67.6 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% from 2012 to 2015, thereafter, followed by non-significant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.8% from 2002 to 2013; 3.2% from 2013 to 2021). The 5-year relative survival between 2017 and 2021 was 72.1%, which contributed to prevalent cases reaching over 2.4 million in 2021.
Conclusion
In 2021, the number of newly diagnosed cancer patients increased as healthcare utilization recovered from the coronavirus disease 2019–related declines of 2020. Revised cancer registration guidelines expanded the registration scope, particularly for stomach and colorectal cancer. Survival rates have improved over the years, leading to a growing population of cancer survivors, necessitating a comprehensive cancer control strategy. The long-term impact of the pandemic on cancer statistics requires future investigation.
4.Prediction of Cancer Incidence and Mortality in Korea, 2023
Kyu-Won JUNG ; Mee Joo KANG ; Eun Hye PARK ; E Hwa YUN ; Hye-Jin KIM ; Hyun-Joo KONG ; Jeong-Soo IM ; Hong Gwan SEO
Cancer Research and Treatment 2023;55(2):400-407
Purpose:
This study aimed to report the projected cancer incidence and mortality for the year 2023 to estimate Korea’s current cancer burden.
Materials and Methods:
Cancer incidence data from 1999 to 2020 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2021 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and then by multiplying the projected age-specific rates by the anticipated age-specific population for 2023. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend.
Results:
In total, 273,076 new cancer cases and 81,818 cancer deaths are expected to occur in Korea in 2023. The most common cancer site is expected to be the lung, followed by the thyroid, breast, colon and rectum, and stomach. These five cancers are expected to represent half of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and gallbladder cancers.
Conclusion
The incidence rates for all types of cancer in Korea are estimated to gradually decrease. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.
5.Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2020
Mee Joo KANG ; Kyu-Won JUNG ; So Hyun BANG ; Seo Hyun CHOI ; Eun Hye PARK ; E Hwa YUN ; Hye-Jin KIM ; Hyun-Joo KONG ; Jeong-Soo IM ; Hong Gwan SEO ;
Cancer Research and Treatment 2023;55(2):385-399
Purpose:
The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2020.
Materials and Methods:
Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2020, with survival follow-up until December 31, 2021. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea.
Results:
The number of new cancer diagnoses in 2020 decreased by 9,218 cases (3.6%) compared to 2019. In 2020, newly diagnosed cancer cases and deaths from cancer were reported as 247,952 (age-standardized rate [ASR], 262.2 per 100,000) and 82,204 (ASR, 69.9 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.0% annually from 2012 to 2015, thereafter, followed by nonsignificant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years. The 5-year relative survival between 2016 and 2020 was 71.5%, which contributed to prevalent cases reaching over 2.2 million in 2020.
Conclusion
In 2020, the number of newly diagnosed cancer patients decreased due to the coronavirus disease 2019 pandemic, but the overall trend is on the rise. Cancer survival rates have improved over the past decades. As the number of cancer survivors increases, a comprehensive cancer control strategy should be implemented in line with the changing aspects of cancer statistics. The long-term impact of the coronavirus disease 2019 pandemic on cancer statistics needs to be investigated in the future.
6.Expression and Clinical Significance of Exosome Derived MiR-181b-5p in Children with Acute Lymphoblastic Leukemia.
Yi HONG ; Kang-Kang LIU ; Ning-Ling WANG ; Zhi-Wei XIE ; Jin-Hua CHU
Journal of Experimental Hematology 2023;31(3):643-648
OBJECTIVE:
To explore the expression level of exosome derived miR-181b-5p in different disease stages of children with acute lymphoblastic leukemia and its relationship with clinical characteristics.
METHODS:
Bone marrow plasma samples of 86 children with ALL were collected. Exosomes were extracted by exosome extraction kit, and RNA in exosomes was extracted by TRIzol method. The levels of miR-181b-5p in the blood plasma exosomes of the patients in the newly diagnosed group, relapse group, remission group and control group were detected by qRT- PCR. The difference of miR-181b-5p expression level in each group was compared and analyzed, and the relationship between miR-181b-5p expression level and clinical characteristics was analyzed.
RESULTS:
The expression level of exosomal miR-181b-5p in the newly diagnosed group and the relapsed group was significantly lower than that in the remission group and the control group (P< 0.05). The expression level of exosomal miR-181b-5p in T-ALL children was higher than that in B-ALL children (P<0.05). The expression level of plasma exosomal miR-181b-5p in male children was higher than that in female children (P<0.01).
CONCLUSION
Exosome derived miR-181b-5p changes dynamically in the course of ALL children, and can be used as a marker miRNA to monitor disease status. Exosomes can transmit information in the tumor microenvironment and serve as a potential carrier for biomolecular targeted therapy.
Humans
;
Male
;
Female
;
Child
;
Exosomes/metabolism*
;
Clinical Relevance
;
MicroRNAs/genetics*
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism*
;
Tumor Microenvironment
7.Regional disparities in major cancer incidence in Korea, 1999-2018
Eun Hye PARK ; Mee Joo KANG ; Kyu-Won JUNG ; Eun Hye PARK ; E Hwa YUN ; Hye-Jin KIM ; Hyun-Joo KONG ; Chang Kyun CHOI ; Jeong-Soo IM ; Hong Gwan SEO ;
Epidemiology and Health 2023;45(1):e2023089-
OBJECTIVES:
This study investigated regional disparities in the incidence of 8 major cancers at the municipal level in Korea during 1999-2018 and evaluated the presence or absence of hot spots of cancer clusters during 2014-2018.
METHODS:
The Korea National Cancer Incidence Database was used. Age-standardized incidence rates were calculated by gender and region at the municipal level for 4 periods of 5 years and 8 cancer types. Regional disparities were calculated as both absolute and relative measures. The possibility of clusters was examined using global Moran’s I with a spatial weight matrix based on adjacency or distance.
RESULTS:
Regional disparities varied depending on cancer type and gender during the 20-year study period. For men, the regional disparities of stomach, colon and rectum, lung, and liver cancer declined, and those of thyroid and prostate cancer recently decreased, despite an overall increasing incidence. For women, regional disparities in stomach, colon and rectum, lung, liver, and cervical cancer declined, that of thyroid cancer recently decreased, despite an overall increasing incidence, and that of breast cancer steadily increased. In 2014-2018, breast cancer (I, 0.61; 95% confidence interval [CI], 0.53 to 0.70) showed a high probability of cancer clusters in women, and liver cancer (I, 0.48; 95% CI, 0.40 to 0.56) showed a high probability of cancer clusters in men.
CONCLUSIONS
Disparities in cancer incidence that were not seen at the national level were discovered at the municipal level. These results could provide important directions for planning and implementing local cancer policies.
8.Comparision of Allogeneic Hematopoietic Stem Cell Transplantation between Children with Thalassemia of Different Ages.
Dong-Liang KANG ; Yong-Hong TAN ; Ya-Mei CHEN ; Jing-Yuan LU ; Jie SHI ; Xiu-Zhen YAN ; Quan-Yi LU
Journal of Experimental Hematology 2022;30(2):539-542
OBJECTIVE:
To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation.
METHODS:
The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups.
RESULTS:
The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups.
CONCLUSION
Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.
Child
;
Child, Preschool
;
Graft vs Host Disease/complications*
;
Hematopoietic Stem Cell Transplantation
;
Humans
;
Quality of Life
;
Retrospective Studies
;
Thalassemia/therapy*
;
beta-Thalassemia/therapy*
9.Effect and Mechanism of Cxcr4 Gene-Modified BMSC-Derived Exosomes on Aplastic Anemia.
Hong-Yang KANG ; Jie LIU ; Zhe CHEN ; Chang-Qing TONG ; Hui-Shu JI ; Qi LI ; Bin ZHANG
Journal of Experimental Hematology 2022;30(3):824-831
OBJECTIVE:
To explore the improvement effect of CXC chemokine receptor 4 (Cxcr4) gene-modified bone marrow mesenchymal stem cell (BMSC)-derived exosomes on aplastic anemia (AA), and make a preliminary exploration of the mechanism.
METHODS:
Mouse BMSCs were isolated and cultured, then infected by recombinant lentivirus carrying Cxcr4 gene. The expression of green fluorescence was observed through fluorescence microscope, the expression of Cxcr4 mRNA was detected by real-time fluorescence quantitative PCR, and the BMSC-derived exosomes modified with Cxcr4 gene were extracted. Mouse models of AA were constructed, and control group, model group (AA), AA+BMSC group, AA+NC-BMSC group, AA+Cxcr4-BMSC group were set up. Except control group and model group, the other three groups of mice were injected 400 μl exosomes from different sources via the tail vein, after 2 weeks, the routine blood indices and the number of bone marrow nucleated cells were detected, the pathological changes of bone marrow were observed by HE staining, and the expression level of Treg cells was detected by flow cytometry.
RESULTS:
Mouse BMSCs were successfully isolated, and BMSCs with high expression of Cxcr4 and their exosomes were obtained. Compared with the control group, the number of red blood cell (RBC), white blood cell (WBC), and platelet (PLT), the hemoglobin (Hb) content and proportion of Treg cells in the peripheral blood of mice in the model group significantly decreased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01). The proliferation level of nucleated cells was low, and the medullary cavity was filled with a large number of fat cells. Compared with the model group, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+BMSC group, AA+NC-BMSC group, and AA+Cxcr4-BMSC group significantly increased (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01), and pathological changes of bone marrow were improved. In addition, the number of RBC, WBC, PLT, the Hb content and proportion of Treg cells in the peripheral blood of mice in the AA+Cxcr4-BMSC group were significantly higher than those in the AA+BMSC group (P<0.01), as well as the number of bone marrow nucleated cells (P<0.01).
CONCLUSION
Injection of Cxcr4 gene-modified BMSC-derived exosomes has a certain improvement effect on AA mice, and the mechanism may be related to an increase of the proportion of Treg cells.
Anemia, Aplastic/metabolism*
;
Animals
;
Bone Marrow Cells
;
Exosomes/metabolism*
;
Humans
;
Mesenchymal Stem Cells
;
Mice
;
Receptors, CXCR4
10.Long-term Prognosis of Mild to Moderate Aortic Stenosis and Coronary Artery Disease
Wonjae LEE ; Wonsuk CHOI ; Si-Hyuck KANG ; In-Chang HWANG ; Hong-Mi CHOI ; Yeonyee E. YOON ; Goo-Yeong CHO
Journal of Korean Medical Science 2021;36(6):e47-
Background:
There is an incomplete understanding of the natural course of mild to moderate aortic stenosis (AS). We aimed to evaluate the natural course of patients with mild to moderate AS and its association with coronary artery disease (CAD).
Methods:
We retrospectively analyzed 787 patients diagnosed with mild to moderate AS using echocardiography between 2004 and 2010. Cardiac death and aortic valve replacement (AVR) for AS were assessed.
Results:
A median follow-up period was 92 months. Compared to the general population, patients with mild to moderate AS had a higher risk of cardiac death (hazard ratio [HR], 17.16; 95% confidence interval [CI], 13.65–21.59; P < 0.001). Established CAD was detected in 22.4% and associated with a significantly higher risk of cardiac mortality (adjusted HR, 1.62; 95% CI, 1.04–2.53; P = 0.033). The risk of cardiac death was lower when patients were taking statin (adjusted HR, 0.64; 95% CI, 0.41–0.98; P = 0.041), which was clear only after 7 years. Both patients with CAD and on statin tended to undergo more AVR, but the difference was not statistically significant (the presence of established CAD; adjusted HR, 1.63; 95% CI, 0.51–3.51; P = 0.214 and the use of statin; adjusted HR, 1.86; 95% CI, 0.76–4.58; P = 0.177).
Conclusion
Mild to moderate AS does not have a benign course. The presence of CAD and statin use may affect the long-term prognosis of patients with mild to moderate AS.

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