1.Causal relationship between circulating inflammatory cytokines and bone mineral density based on two-sample Mendelian randomization
Shuai CHEN ; Jie JIN ; Huawei HAN ; Ningsheng TIAN ; Zhiwei LI
Chinese Journal of Tissue Engineering Research 2025;29(8):1556-1564
BACKGROUND:Many recent studies have shown a close relationship between inflammatory cytokines and osteoporosis and bone mineral density(BMD).However,the causal relationship between inflammatory cytokines and BMD has not been fully revealed. OBJECTIVE:To explore the potential causal relationship between inflammatory cytokines and BMD using a two-sample Mendelian randomization analysis. METHODS:The single nucleotide polymorphisms associated with 41 circulating inflammatory cytokines were selected from the open database of genome-wide association studies(GWAS)as instrumental variables.The GWAS data about BMD were from the Genetic Factors for Osteoporosis Consortium,involving a total of 32 735 individuals of European ancestry.Inverse variance weighting was used as the primary analysis to evaluate the causal effect.Weighted median,MR Egger regression,simple mode,and weighted mode methods were used to supplement the explanation.We used the MR-Egger intercept and MR-PRESSO method to conduct a pleiotropy test,the Cochran's Q test was used to determine whether there was heterogeneity in the results,and the leave-one-out method was used to evaluate the stability of the results.In addition,to more accurately assess the causality,the Bonferroni-corrected test was used to identify inflammatory cytokines that have a strong causal relationship with BMD. RESULTS AND CONCLUSION:(1)According to the results of the inverse variance weighting method,we found a positive causal relationship between interleukin-8 and lumbar spine BMD[β=0.075,95%confidence interval(CI):0.033-0.117,P=0.000 5),while a negative causal relationship between interleukin-17 and lumbar spine BMD(β=-0.083,95%CI:-0.152 to-0.014,P=0.018).There might be a negative causal relationship between tumor necrosis factor b and femoral neck BMD(β=-0.053,95%CI:-0.088 to-0.018,P=0.003),while a positive causal relationship between basic fibroblast growth factor and femoral neck BMD(β=0.085,95%CI:0.016-0.154,P=0.015).There might be a negative causal relationship between macrophage inflammatory protein-1a and total body BMD(β=-0.056,95%CI:-0.105 to-0.007,P=0.025).There was a negative causal relationship between interleukin-5(β=-0.019,95%CI:-0.031 to-0.006,P=0.004),stromal cell-derived factor-1a(β=-0.022,95%CI:-0.038 to-0.005,P=0.010),hepatocyte growth factor(β=-0.021,95%CI:-0.041 to-0.002,P=0.030),interleukin-4(β=-0.016,95%CI:-0.032 to-0.001,P=0.034)and heel BMD,while a positive causal relationship between nerve growth factor(β=0.019,95%CI:0.002-0.036,P=0.033),granulocyte colony-stimulating factor(β=0.011,95%CI:0.000-0.022,P=0.050),and heel BMD.Meanwhile,after the Bonferroni-corrected test,there was a strong positive causal effect between interleukin-8 and lumbar spine BMD(P=0.000 5).And consistent directional effects for all analyses were observed in MR Egger,weighted median,simple mode,and weighted mode methods.(2)Sensitivity analyses revealed no heterogeneity,pleiotropy,or outliers for the causal effect of circulating inflammatory cytokines on BMD.
2.Persistent influence of past obesity on current adiponectin levels and mortality in patients with type 2 diabetes
Min-Ji KIM ; Sung-Woo KIM ; Bitna HA ; Hyang Sook KIM ; So-Hee KWON ; Jonghwa JIN ; Yeon-Kyung CHOI ; Keun-Gyu PARK ; Jung Guk KIM ; In-Kyu LEE ; Jae-Han JEON
The Korean Journal of Internal Medicine 2025;40(2):299-309
Background/Aims:
Adiponectin, a hormone primarily produced by adipocytes, typically shows an inverse relationship with body mass index (BMI). However, some studies have reported a positive correlation between the two. Thus, this study aimed to examine the relationship between adiponectin level and BMI in diabetic patients, focusing on the impact of past obesity on current adiponectin levels.
Methods:
We conducted an observational study analyzing data from 323 diabetic patients at Kyungpook National University Hospital. Based on past and current BMIs, participants were categorized into never-obese (nn, n = 106), previously obese (on, n = 43), and persistently obese (oo, n = 73) groups based on a BMI threshold of 25 kg/m2. Adiponectin level and BMI were key variables. Kaplan–Meier analysis assessed their impact on all-cause mortality up to August 2023, with survival differences based on adiponectin quartiles and follow-up starting from patient enrollment (2010–2015).
Results:
The analysis revealed a significant inverse correlation between adiponectin level and past maximum BMI. The on group exhibited approximately 10% lower adiponectin levels compared to the nn group. This association remained significant after adjusting for current BMI, age, and sex, highlighting the lasting influence of previous obesity on adiponectin levels. Furthermore, survival analysis indicated that patients in the lowest adiponectin quartile had reduced survival, with a statistically significant trend (p = 0.062).
Conclusions
Findings of this study suggest that lower adiponectin levels, potentially reflecting past obesity, are associated with decreased survival in diabetic patients, underscoring a critical role of adiponectin in long-term health outcomes.
3.Sex-specific impact of the COVID-19 outbreak on the incidence of metabolic syndrome: a comparative study of 2018–2019 and 2020–2021
Kyeong-Hyeon CHUN ; Hyun-Jin KIM ; Dae Ryong KANG ; Jang Young KIM ; Wonjin KIM ; Yong Whi JEONG ; Seung Hwan HAN ; Kwang Kon KOH ;
The Korean Journal of Internal Medicine 2025;40(2):262-274
Background/Aims:
The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global health, exacerbated metabolic health issues, and altered lifestyle behaviors. This study examined the sex-specific impact of the COVID-19 outbreak on the incidence of metabolic syndrome using data from the Korea National Health and Nutrition Examination Survey (KNHANES).
Methods:
Data from the KNHANES VII (2018) and VIII (2019–2021), including 15,499 participants, were analyzed. The study population was stratified by sex, and further subdivisions were conducted based on the timeframe relative to the COVID-19 outbreak. Variables such as age, education level, household income, smoking status, and high-risk drinking were analyzed to assess their influence on the prevalence of metabolic syndrome.
Results:
The overall prevalence of metabolic syndrome significantly increased from 28.11% before the outbreak to 29.69% after the outbreak. Both males and females reported significant increases in waist circumference and fasting glucose levels. Age and education level differentially influenced the prevalence of metabolic syndrome between the sex. Smoking was significantly associated with increased prevalence in males, whereas high-risk drinking was associated with increased prevalence in males and decreased prevalence in females.
Conclusions
The COVID-19 pandemic has significantly increased the prevalence of metabolic syndrome with notable sex-specific differences. These findings highlight the need for sex-specific public health interventions to mitigate the impact of the pandemic on metabolic health.
4.Rosuvastatin activates autophagy via inhibition of the Akt/mTOR axis in vascular smooth muscle cells
Seongpyo LEE ; Do-Hyung LEE ; Jin-Pyo LEE ; Joo-Hui HAN
The Korean Journal of Physiology and Pharmacology 2025;29(1):117-126
The proliferation and migration of vascular smooth muscle cells (VSMCs) are key contributors to the development of atherosclerosis and restenosis. We investigated the impact of rosuvastatin (RSV) on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, with a focus on the Akt/mTORautophagy signaling pathways. The cytotoxicity of RSV was assessed using MTT and annexin V staining, while the proliferation and migration capabilities of PDGF-BBinduced VSMCs were evaluated using MTT and cell migration assays. Confocal microscopy was employed to examine autophagic cell images, and protein expressions were analyzed via Western blotting. Our key findings revealed that RSV inhibited PDGF-BB-induced proliferation and migration of VSMCs, significantly reducing the expression of proliferating cell nuclear antigen and matrix metalloproteinase-2, which are crucial for these processes. RSV also enhanced autophagy in PDGF-BBstimulated cells by inducing the maturation of microtubule-associated protein light chain 3 and increasing the expression of Beclin-1, autophagy related (Atg)3, Atg5, and Atg7. The regulatory effects of RSV on PDGF-BB-induced autophagy, proliferation, and migration were associated with the suppression of the Akt/mTOR signaling pathway. These findings suggest that RSV may have potential therapeutic benefits in preventing and treating vascular diseases by targeting the Akt/mTOR pathway and inducing autophagy.
5.Efficacy of Bone Regeneration Cell Therapy Using Mesenchymal Stem Cells Originating from Embryonic Stem Cells in Animal Models; Bone Defects and Osteomyelitis
Jin-Ho PARK ; Han-Sol BAE ; Ingeun KIM ; Jiwoon JUNG ; Yoonho ROH ; Dongbin LEE ; Tae Sung HWANG ; Hee-Chun LEE ; June-Ho BYUN
Tissue Engineering and Regenerative Medicine 2025;22(1):145-157
BACKGROUND:
Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture.
METHODS:
This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DWMSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts.
RESULTS:
Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring.
CONCLUSION
Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.
6.Comparison of Anticancer Effects of Histone Deacetylase Inhibitors CG-745 and Suberoylanilide Hydroxamic Acid in Non-small Cell Lung Cancer
Hyo Jin KIM ; Ui Ri AN ; Han Jee YOON ; Hyun LIM ; Ki Eun HWANG ; Young Suk KIM ; Hak Ryul KIM
Tuberculosis and Respiratory Diseases 2025;88(2):342-352
Background:
Histone deacetylase (HDAC) inhibition offers potential anticancer effects across diverse cancers due to HDAC's significant role in cancer development and progression. Consequently, we demonstrated the therapeutic efficacy of the novel HDAC inhibitor, CG-745, in comparison with existing inhibitors such as suberoylanilide hydroxamic acid (SAHA) in non-small cell lung cancer (NSCLC) cells.
Methods:
CG-745's effect on apoptosis and reactive oxygen species (ROS)-dependent mitochondrial dysfunction was investigated using annexin V assay, MitoSoX, and Western blot in human A549 and H460 cells. Additionally, HDAC expression was analyzed through real-time polymerase chain reaction. We also evaluated the inhibitory effect of CG-745 on epithelial-mesenchymal transition (EMT) induced by transforming growth factor β1 (TGF-β1) via Western blot, scratch analysis, and matrigel invasion analysis.
Results:
Compared to SAHA, CG-745 inhibited cell viability and mRNA expression of HDACs such as HDAC1, HDAC2, HDAC3, and HDAC8. It also induced apoptosis, ROS, and mitochondrial dysfunction in a concentration-dependent manner. CG-745 reversed EMT triggered by TGF-β1 in A549 and H460 cells, and curtailed the migration and invasion enhanced by TGF-β1. CG-745 has demonstrably inhibited EMT and induced apoptosis in NSCLC cells.
Conclusion
CG-745 may represent a novel therapeutic strategy for NSCLC treatment.
7.18F‑FDG PET/CT in Inflammation and Infection: Procedural Guidelineby the Korean Society of Nuclear Medicine
Joon Ho CHOI ; Yong‑Jin PARK ; Hyunjong LEE ; Hye Ryeong KWON ; Jinkyoung OH ; Chae Hong LIM ; Eun Ji HAN ; Joon Young CHOI ;
Nuclear Medicine and Molecular Imaging 2025;59(1):27-40
This guideline outlines the use of 18F-fluoro-2-deoxyglucose positron emission tomography / computed tomography for the diagnosis and management of infectious and inflammatory diseases. It provides detailed recommendations for healthcare providers on patient preparation, imaging procedures, and the interpretation of results. Adapted from international standards and tailored to local clinical practices, the guideline emphasizes safety, quality control, and effective use of the technology in various conditions, including spinal infections, diabetic foot, osteomyelitis, vasculitis, and cardiac inflammation. The aim is to assist nuclear medicine professionals in delivering accurate diagnoses and improving patient outcomes while allowing flexibility to adapt to individual patient needs, technological advancements, and evolving medical knowledge. This document is a comprehensive resource for enhancing the quality and safety of 18F-fluoro-2-deoxyglucose positron emission tomography / computed tomography for the evaluation of infectious and inflammatory diseases.Preamble The Korean Society of Nuclear Medicine (KSNM) was established in 1961 to promote the clinical and technological advancement of nuclear medicine in South Korea, with members that include nuclear medicine physicians and associated scientists. The KSNM regularly formulates and revises procedural guidelines for nuclear medicine examinations to enhance the field and improve the quality of patient care. These guidelines are designed to support healthcare professionals in providing appropriate medical care to patients. However, they are not immutable rules or mandatory requirements for conducting examinations.Therefore, KSNM states that these guidelines should not be used in legal actions challenging a healthcare professional’s medical decisions. The ultimate judgment regarding specific procedures or appropriate measures should be made by nuclear medicine physicians, considering the unique circumstances of each case. Deviation from these guidelines does not imply substandard medical practice. Rather, reasonable judgments differing from the guidelines can be made based on the patient’s condition, available resources, and advancements in knowledge or technology. Due to the diversity and complexity of patients, it is often challenging to predict the most appropriate diagnostic and accurate therapeutic responses. Thus, adherence to these guidelines does not always guarantee an exact diagnosis or successful outcomes.The purpose of this guideline is to assist healthcare providers in making reasonable decisions and conducting effective and safe examinations based on current medical knowledge, available resources, and patient needs when performing 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) examinations for infectious/ inflammatory diseases.
8.Erratum: Induction of apoptotic cell death in human bladder cancer cells by ethanol extract of Zanthoxylum schinifolium leaf, through ROSdependent inactivation of the PI3K/ Akt signaling pathway
Cheol PARK ; Eun Ok CHOI ; Hyun HWANGBO ; Hyesook LEE ; Jin-Woo JEONG ; Min Ho HAN ; Sung-Kwon MOON ; Seok Joong YUN ; Wun-Jae KIM ; Gi-Young KIM ; Hye-Jin HWANG ; Yung Hyun CHOI
Nutrition Research and Practice 2025;19(2):328-330
9.Resveratrol attenuates aging-induced mitochondrial dysfunction and mitochondria-mediated apoptosis in the rat heart
Youngju CHOI ; Mi-Hyun NO ; Jun-Won HEO ; Eun-Jeong CHO ; Dong-Ho PARK ; Ju-Hee KANG ; Chang-Ju KIM ; Dae Yun SEO ; Jin HAN ; Hyo-Bum KWAK
Nutrition Research and Practice 2025;19(2):186-199
RESULTS:
Resveratrol significantly reduced cardiac hypertrophy and remodeling in aging hearts. In addition, resveratrol significantly ameliorated aging-induced mitochondrial dysfunction (e.g., decreased oxygen respiration and increased hydrogen peroxide emission) and mitochondria-dependent apoptotic signaling (the Bax/Bcl-2 ratio, mitochondrial permeability transition pore opening sensitivity, and cleaved caspase-3 protein levels).Resveratrol also significantly attenuated aging-induced apoptosis (determined via cleaved caspase-3 staining and TUNEL-positive myonuclei) in cardiac muscles.
CONCLUSION
This study demonstrates that resveratrol treatment has a beneficial effect on aging-induced cardiac remodeling by ameliorating mitochondrial dysfunction and inhibiting mitochondria-mediated apoptosis in the heart.
10.Microbiological and clinical characteristics of vulvovaginitis in premenarcheal and postmenarcheal girls in a tertiary center in South Korea
Soo Jin PARK ; Ki Wook YUN ; Ji Yeon HAN ; Sung Woo KIM ; Jae Hyeon PARK ; Hoon KIM ; Eun Hwa CHOI ; Seung-Yup KU
Obstetrics & Gynecology Science 2025;68(2):163-173
Objective:
To analyze the microbiological and clinical characteristics of vulvovaginitis in girls, distinguishing between the premenarcheal and postmenarcheal groups in a tertiary center in South Korea.
Methods:
This retrospective cohort study included 195 patients under 20 years of age diagnosed with vulvovaginitis at a tertiary hospital between 2014 and 2023. The patients were categorized into premenarcheal (n=95) and postmenarcheal (n=100) groups. Data on initial symptoms, microbial cultures, and treatment methods were analyzed.
Results:
The most common initial symptom was vaginal discharge, reported in 63.1% of cases. Culture results showed a 51.3% positivity rate for any microorganism, with a prevalence of gram-negative rods (32.8%) and gram-positive cocci (14.4%). The most frequently isolated microorganisms were Escherichia coli (17.9%), Candida albicans (7.7%), and Enterococcus faecalis (6.7%). Gram-negative rods were more common in the premenarcheal group (37.1% vs. 25.0%; p=0.01). No significant differences were observed in the prevalence of gram-positive cocci and Candida species between the two groups (16.8% vs. 12.0%, p=0.22; 6.3% vs. 13.0%, p=0.09; respectively). The susceptibilities of grampositive microorganisms to penicillin, oxacillin, clindamycin, vancomycin, and tetracycline were 58.8%, 58.3%, 94.7%, 100.0%, and 73.7%, respectively. The susceptibilities of gram-negative microorganisms to amoxicillin/clavulanic acid, ciprofloxacin, ceftriaxone, and nitrofurantoin were 89.3%, 85.3%, 76.0%, and 100.0%, respectively.
Conclusion
This study identified differences in the microbial profiles associated with vulvovaginitis between premenarcheal and postmenarcheal girls. Age-specific and history-based clinical approaches tailored to menarcheal status are warranted to improve the management and outcomes of pediatric and adolescent vulvovaginitis.

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