👤 Sinai Kim

Uncovering a Glaucoma-Linked Lysophosphatidic Acid-MAPK/AP-1 Fibrosis Axis in Human Trabecular Meshwork Cells and Its Modulation by

Youngsic Jeon, Hyukjoon Kwon, Hong Ryul Ahn +8 more · 2026 · International journal of molecular sciences · MDPI · added 2026-04-24

Youngsic Jeon, Hyukjoon Kwon, Hong Ryul Ahn, Gyuwon Huh, Taejung Kim, Young-Tae Park, Hyun Bong Park, Jin-Hyoung Jeong, Jae-Hyun Jo, Young-Joo Kim, Sang Hoon Jung Show less

Dysregulated extracellular matrix (ECM) deposition and epithelial-mesenchymal transition (EMT) in the trabecular meshwork (TM) contribute to glaucoma-associated fibrotic remodeling, and lysophosphatid Show more

Dysregulated extracellular matrix (ECM) deposition and epithelial-mesenchymal transition (EMT) in the trabecular meshwork (TM) contribute to glaucoma-associated fibrotic remodeling, and lysophosphatidic acid (LPA) potently induces these profibrotic responses in human trabecular meshwork (HTM) cells. We investigated whether an ethanolic extract of Show less

📄 PDF DOI: 10.3390/ijms27031544

A Position Paper on Lipoprotein(a) From the Lipoprotein(a) Task Force of the Korean Society of Lipid and Atherosclerosis: Current Evidence, Clinical Applications, and Future Directions.

Youngwoo Jang, Jang Hoon Lee, Sang-Guk Lee +5 more · 2026 · Journal of lipid and atherosclerosis · added 2026-04-24

Youngwoo Jang, Jang Hoon Lee, Sang-Guk Lee, Hun Jee Choe, Sang Min Park, In-Kyung Jeong, Byung Jin Kim, Lipoprotein(a) Task Force of the Korea Society of Lipid and Atherosclerosis Show less

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS), with plasma levels largely unaffected by li Show more

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS), with plasma levels largely unaffected by lifestyle modification or conventional lipid-lowering therapy. Although international guidelines increasingly recognize Lp(a) as a risk-enhancing factor, in many Asian populations thresholds for high Lp(a) and treatment strategies remain undefined. This Korean position paper, developed by the Lp(a) Task Force of the Korean Society of Lipid and Atherosclerosis, presents an evidence-based summary of the pathophysiology, clinical relevance, and therapeutic landscape surrounding Lp(a), with a focus on Korean-specific data. It reviews the genetic architecture of Lp(a), ethnic variability in concentrations, and its mechanistic roles in inflammation, thrombosis, and calcification. Based on large Korean cohorts, a 3-tiered classification is proposed of normal (<30 mg/dL), borderline high (30-49 mg/dL), and high (≥50 mg/dL), harmonizing global thresholds with local data. The document also highlights the limitations of current Lp(a) assays in Korea, and calls for standardized, isoform-insensitive testing. Novel therapeutics, including antisense oligonucleotides, small interfering RNAs, and small molecular inhibitors, have shown promising Lp(a)-lowering effects, with multiple phase 3 trials currently ongoing, or in planning. Given the unmet clinical need, the paper recommends incorporating Lp(a) into cardiovascular risk assessment, and calls for Korean-specific longitudinal studies, national screening strategies, and participation in clinical trials. These efforts will help clarify Lp(a)-associated risk in Korean patients and guide the adoption of future targeted therapies. Show less

📄 PDF DOI: 10.12997/jla.2026.15.1.2

Genetically Predicted Levels of Lipoprotein(a) and Risk of Cerebrovascular Disease.

Iyas Daghlas, Marios K Georgakis, Benoit J Arsenault +3 more · 2026 · Journal of the American Heart Association · added 2026-04-24

Iyas Daghlas, Marios K Georgakis, Benoit J Arsenault, Anthony S Kim, Stephen Burgess, Dipender Gill Show less

Lipoprotein(a) (Lp(a)) is a highly atherogenic lipoprotein and the target of investigational therapies. Using a Mendelian randomization study design, we aimed to clarify associations between genetical Show more

Lipoprotein(a) (Lp(a)) is a highly atherogenic lipoprotein and the target of investigational therapies. Using a Mendelian randomization study design, we aimed to clarify associations between genetically predicted Lp(a) levels and cerebrovascular disease outcomes and related phenotypes. We obtained genetic associations with Lp(a) levels ( Genetically predicted Lp(a) levels associated with significantly increased risk of all-cause ischemic stroke (odds ratio [OR], 1.04 [95% CI, 1.02-1.07], Elevated Lp(a) is primarily associated with ischemic stroke due to large artery atherosclerosis, while showing no link to cerebral small vessel disease. These findings support prioritization of patients with atherosclerotic cerebrovascular disease in Lp(a)-lowering stroke prevention trials. Show less

📄 PDF DOI: 10.1161/JAHA.125.045423

A Position Paper on Lipoprotein(a) From the Lipoprotein(a) Task Force of the Korean Society of Lipid and Atherosclerosis: Current Evidence, Clinical Applications, and Future Directions.

Youngwoo Jang, Jang Hoon Lee, Sang-Guk Lee +5 more · 2026 · Korean circulation journal · added 2026-04-24

Youngwoo Jang, Jang Hoon Lee, Sang-Guk Lee, Hun Jee Choe, Sang Min Park, In-Kyung Jeong, Byung Jin Kim, Lipoprotein(a) Task Force of the Korea Society of Lipid and Atherosclerosis Show less

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS), with plasma levels largely unaffected by li Show more

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS), with plasma levels largely unaffected by lifestyle modification or conventional lipid-lowering therapy. Although international guidelines increasingly recognize Lp(a) as a risk-enhancing factor, in many Asian populations thresholds for high Lp(a) and treatment strategies remain undefined. This Korean position paper, developed by the Lp(a) Task Force of the Korean Society of Lipid and Atherosclerosis, presents an evidence-based summary of the pathophysiology, clinical relevance, and therapeutic landscape surrounding Lp(a), with a focus on Korean-specific data. It reviews the genetic architecture of Lp(a), ethnic variability in concentrations, and its mechanistic roles in inflammation, thrombosis, and calcification. Based on large Korean cohorts, a 3-tiered classification is proposed of normal (<30 mg/dL), borderline high (30-49 mg/dL), and high (≥50 mg/dL), harmonizing global thresholds with local data. The document also highlights the limitations of current Lp(a) assays in Korea, and calls for standardized, isoform-insensitive testing. Novel therapeutics, including antisense oligonucleotides, small interfering RNAs, and small molecular inhibitors, have shown promising Lp(a)-lowering effects, with multiple phase 3 trials currently ongoing, or in planning. Given the unmet clinical need, the paper recommends incorporating Lp(a) into cardiovascular risk assessment, and calls for Korean-specific longitudinal studies, national screening strategies, and participation in clinical trials. These efforts will help clarify Lp(a)-associated risk in Korean patients and guide the adoption of future targeted therapies. Show less

📄 PDF DOI: 10.4070/kcj.2025.0388

Is Lower Pole Access Safer for Ultrasound-Guided Supine Percutaneous Nephrolithotomy?

Ziv Savin, Linda Dayan Rahmani, Eve Frangopoulos +10 more · 2026 · Urology practice · added 2026-04-24

Ziv Savin, Linda Dayan Rahmani, Eve Frangopoulos, Vinay Durbhakula, Asher Mandel, Juan S Serna, Aubrey Dibello, Esther Kim, Adam Daniel Geffner, Kavita Gupta, Blair Gallante, William M Atallah, Mantu Gupta Show less

Ultrasound (US)-guided supine percutaneous nephrolithotomy (PCNL) is increasingly being adopted. The aim of this study was to assess the safety of lower vs non-lower pole access (non-LPa) in supine US Show more

Ultrasound (US)-guided supine percutaneous nephrolithotomy (PCNL) is increasingly being adopted. The aim of this study was to assess the safety of lower vs non-lower pole access (non-LPa) in supine US-guided PCNL. This study was a retrospective cohort analysis of 228 patients who underwent single-access US-guided supine PCNL between March 2023 and June 2024 and were categorized into lower (n = 162), interpolar (n = 42), and upper pole (n = 21) access categories. Baseline demographics, stone characteristics, and intraoperative details were analyzed and compared between the groups. Safety outcomes, including 30-day postoperative total and major complications (based on Clavien-Dindo classification), as well as pain scores, were compared between lower pole access (LPa) and non-LPa. Baseline clinical and stone characteristics were comparable between the groups. Non-LPa was more frequently performed on the right side ( When performing US-guided supine PCNL, LPa has a superior safety profile, resulting in fewer major and total complications compared with non-LPa. Show less

no PDF DOI: 10.1097/UPJ.0000000000000970

Engineering Native-like GPCR Antigens Enables Discovery of an LPA2-Blocking Antibody for Ovarian Cancer.

Jin Kim, Dong Wook Shin, Jiyoung Lee +4 more · 2026 · ACS synthetic biology · ACS Publications · added 2026-04-24

Jin Kim, Dong Wook Shin, Jiyoung Lee, Min Ji Lee, Yeon Gyu Yu, Dae-Hee Lee, Tae Hyun Kang Show less

G-protein-coupled receptors (GPCRs) are high-value therapeutic targets, yet antibody discovery remains limited by difficulties in preparing antigens that preserve native conformations. Here, we engine Show more

G-protein-coupled receptors (GPCRs) are high-value therapeutic targets, yet antibody discovery remains limited by difficulties in preparing antigens that preserve native conformations. Here, we engineered a native-like, full-length human LPA2 antigen by combining N-terminal P9* fused with amphipathic poly-γ-glutamate (APG) stabilization, affording an antigen suitable for the selection of antibodies with therapeutic efficacy. By screening a large synthetic human scFv library, we isolated an antagonistic antibody against LPA2 that bound LPA2 selectively over LPA1 (EC Show less

no PDF DOI: 10.1021/acssynbio.5c00742

ApoJ regulates endothelial lipase activity and stability.

Uriel L Jean-Baptiste, Simcha R Singh, Ming J Wu +3 more · 2026 · Protein science : a publication of the Protein Society · Wiley · added 2026-04-24

Uriel L Jean-Baptiste, Simcha R Singh, Ming J Wu, Kellen Christina da Cruz Rodriguez, Young-Bum Kim, Saskia B Neher Show less

Endothelial lipase (EL) is a key regulator of high-density lipoprotein (HDL) metabolism. Many aspects of EL function remain incompletely understood due to challenges in purifying active EL. This study Show more

Endothelial lipase (EL) is a key regulator of high-density lipoprotein (HDL) metabolism. Many aspects of EL function remain incompletely understood due to challenges in purifying active EL. This study identifies apolipoprotein J (ApoJ) as a novel chaperone for EL, crucial for its solubility and activity. Using an optimized purification protocol that yields active EL, we discovered that ApoJ consistently co-purifies with EL, maintaining its activity. We further show that knocking down ApoJ decreases the activity of EL. We demonstrate that ApoJ interacts with EL via its hydrophobic lid and tryptophan loop regions, and that mutating these regions abolishes the effect of ApoJ on the solubility and activity of EL. We show that ApoJ, EL, and ApoA1 (the defining lipoprotein of HDL particles) colocalize in HDL particles in mouse plasma. However, we find that ApoJ is not a direct carrier for EL to HDL particles. Instead, our data suggest that ApoJ primarily serves to enhance EL activity through its role as a chaperone, even when incorporated into lipid substrates. Our findings suggest a model in which ApoJ protects EL in plasma and enhances its hydrolysis of lipoprotein substrates. We propose that ApoJ is an accessory protein for EL, analogous to GPIHBP1 for LPL and co-lipase for PL. Further study of the interaction between EL and ApoJ will promote a better understanding of HDL metabolism. Show less

📄 PDF DOI: 10.1002/pro.70518

LPL

Non-remnant triglyceride-rich lipoproteins due to lipoprotein lipase deficiency increase atherosclerosis in mice.

Ainara G Cabodevilla, Maria Concepcion Izquierdo, Debapriya Basu +12 more · 2026 · Nature communications · Nature · added 2026-04-24

Ainara G Cabodevilla, Maria Concepcion Izquierdo, Debapriya Basu, Waqas Younis, Munichandra Babu Tirumalasetty, Qing Robert Miao, Dimitris Nasias, Jenny E Kanter, Tse Wing Winnie Ho, Jana Gjini, Edward Fisher, Jeffrey Kim, Warren L Lee, Karin Bornfeldt, Ira J Goldberg Show less

Increased fasting and postprandial triglyceride levels are risk factors for cardiovascular disease (CVD). Partially metabolized triglyceride-rich lipoproteins (TRLs) termed remnants are created when i Show more

Increased fasting and postprandial triglyceride levels are risk factors for cardiovascular disease (CVD). Partially metabolized triglyceride-rich lipoproteins (TRLs) termed remnants are created when intestinally-derived chylomicrons and liver secreted very low density lipoproteins (VLDLs) interact with lipoprotein lipase (LpL) situated on the luminal surface of capillary endothelial cells. Higher circulating remnant levels have been implicated as the reason for the relationship between TRL levels and CVD. We hypothesized that nascent lipoproteins not only remnants are atherogenic. To test this, we created mice with induced whole-body lipoprotein lipase (LpL) deficiency combined with LDL receptor (LDLR) deficiency. On an atherogenic Western-type diet (WD), male and female mice with induced global LpL deficiency (iLpl Show less

📄 PDF DOI: 10.1038/s41467-025-68193-3

LPL

Ovomucoid hydrolysates prepared using alcalase suppress adipogenesis at an early stage of 3T3-L1 cell differentiation.

Seung-Woo Yu, Hyeong-Jin Kim, Su-Yeon Song +4 more · 2026 · Enzyme and microbial technology · Elsevier · added 2026-04-24

Seung-Woo Yu, Hyeong-Jin Kim, Su-Yeon Song, Kee-Tae Kim, Dong Uk Ahn, Na-Kyoung Lee, Hyun-Dong Paik Show less

The effects of ovomucoid (OVM), a by-product of egg white, and its hydrolysates on adipocyte differentiation and lipid accumulation were investigated. The OVM hydrolyzed using Alcalase® and pepsin was Show more

The effects of ovomucoid (OVM), a by-product of egg white, and its hydrolysates on adipocyte differentiation and lipid accumulation were investigated. The OVM hydrolyzed using Alcalase® and pepsin was named AH and PH, respectively. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis revealed significant changes in molecular weight of both hydrolysates, with AH showing a higher degree of hydrolysis. AH exhibited a more pronounced inhibitory effect on fat accumulation than PH. In in vitro experiments, AH and PH suppressed lipid accumulation during 3T3-L1 adipocyte differentiation, with AH inhibiting lipid accumulation most effectively. Oil red O staining and triglyceride measurements revealed lipid reduction in AH-treated cells, indicating that AH plays a major role in preventing lipid accumulation in adipocytes. In addition, AH inhibited the expression of lipid transcription factors (CCAAT/enhancer-binding protein alpha (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding proteins (SREBP-1c)), adipogenesis-related factors (fatty acid synthase (FAS) and ACC1), insulin-related factors (insulin receptor substrate (IRS2) and protein kinase B (AKT2)), and lipolysis-related factors (glycerol-3-phosphate acyltransferase (GPAT), CD36, and lipoprotein lipase (LPL)) in a concentration-dependent manner. Specifically, the effect of AH was most pronounced in the early stages of adipocyte differentiation, where it activated AMPK early to associate energy homeostasis and downregulate genes important for cell cycle and lipid formation. This study suggests that OVM hydrolysates prepared using Alcalase® may contribute to the development of new strategies for the obesity treatment market. Show less

no PDF DOI: 10.1016/j.enzmictec.2025.110781

LPL

Detection of Fusion Genes Using RNA Sequencing in Acute Leukemia.

Hyun-Young Kim, Boram Kim, Min-Seung Park +6 more · 2026 · Annals of laboratory medicine · added 2026-04-24

Hyun-Young Kim, Boram Kim, Min-Seung Park, Jong-Ho Park, Hee Young Ju, Keon Hee Yoo, Jun Ho Jang, Chul Won Jung, Hee-Jin Kim Show less

Fusion genes are major drivers of acute leukemia. Conventional diagnostics are limited in detecting the diverse fusions included in recently updated acute leukemia classifications. We evaluated the fu Show more

Fusion genes are major drivers of acute leukemia. Conventional diagnostics are limited in detecting the diverse fusions included in recently updated acute leukemia classifications. We evaluated the fusion detection performance of RNA sequencing (RNA-seq) compared with that of conventional diagnostics in patients with acute leukemia. We retrospectively obtained the data of 101 patients with acute leukemia who underwent conventional diagnostics (i.e., karyotyping, FISH, or multiplex reverse transcription PCR) at diagnosis at Samsung Medical Center, Seoul, Korea, between September 2022 and September 2023. Whole RNA-seq was performed using the Illumina Stranded mRNA Prep kit (Illumina, San Diego, CA, USA). The concordance, sensitivity, and specificity of RNA-seq for fusion gene detection were compared with those of conventional diagnostics. RNA-seq helped identify 52 fusion genes in 51 (50.5%) of 101 patients, with detection rates of 40.7%, 70.3%, 37.5%, and 50% in acute myeloid leukemia, B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia, respectively. RNA-seq showed 83.3% sensitivity and 80.8% concordance with conventional diagnostics; it missed eight fusions, likely because of low transcript abundance or enhancer hijacking. RNA-seq also helped clarify three previously unspecified rearrangements and detected 12 fusions (21.4%) in 56 cases that tested negative with conventional diagnostics, including four novel ( This was the first study to evaluate the performance of whole RNA-seq in fusion detection in patients with acute leukemia in Korea. Incorporating RNA-seq into diagnostic workflows may facilitate earlier and more precise therapeutic decisions and improve prognostic assessment in patients with acute leukemia. Show less

📄 PDF DOI: 10.3343/alm.2025.0300

MLLT10

Unaltered empathy-related behaviors in Williams-Beuren syndrome mouse models.

Dahm So, Hye Lim Cha, Sua Lee +3 more · 2026 · Molecular brain · BioMed Central · added 2026-04-24

Dahm So, Hye Lim Cha, Sua Lee, Sowon Kim, Eunsu Yoo, Sehoon Keum Show less

Williams-Beuren Syndrome (WBS), a neurodevelopmental disorder caused by a heterozygous microdeletion at chromosome 7q11.23, is characterized by hypersociability and enhanced affective empathy. However Show more

Williams-Beuren Syndrome (WBS), a neurodevelopmental disorder caused by a heterozygous microdeletion at chromosome 7q11.23, is characterized by hypersociability and enhanced affective empathy. However, the specific genetic and neural mechanisms within the WBS locus underlying this elevated empathic response remain unknown. Here, we investigated empathy-related behaviors, including observational fear and allogrooming, in WBS mouse models harboring a deletion within the conserved syntenic region on mouse chromosome 5. We demonstrate that WBS mice exhibited emotional contagion and prosocial consolation behaviors comparable to their wild-type controls. Furthermore, WBS mice with single-gene deletions of the cortex-enriched genes Abhd11, Limk1, Mlxipl, and Stx1a also showed unaffected empathic freezing behavior. Collectively, our findings suggest that the enhanced empathic responsiveness reported in individuals with WBS may be influenced by reduced social inhibition toward others, while acknowledging that limitations of current rodent behavioral assays preclude definitive conclusions regarding primary neural mechanisms of empathy. Show less

📄 PDF DOI: 10.1186/s13041-026-01278-2

MLXIPL

The prevalence of pathogenic variants in medically actionable genes among individuals with idiopathic hypogonadotropic hypogonadism/Kallmann syndrome.

Jaclyn M Kwal, Lynn P Chorich, Anna Navitski +5 more · 2026 · Journal of assisted reproduction and genetics · Springer · added 2026-04-24

Jaclyn M Kwal, Lynn P Chorich, Anna Navitski, Zoe Hawkins, Lindsey Grater, Hugh S Taylor, Hyung-Goo Kim, Lawrence C Layman Show less

Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are rare reproductive disorders with known genetic heterogeneity. Using exome sequencing, our group previously reported the pr Show more

Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are rare reproductive disorders with known genetic heterogeneity. Using exome sequencing, our group previously reported the prevalence of pathogenic and likely pathogenic (P/LP) variants in genes causing IHH/KS as the primary endpoint of our study. Here, we investigate the frequency of secondary findings (SF) to determine whether individuals with IHH/KS harbor an increased burden of P/LP variants in medically actionable genes (MAGs) defined by the American College of Medical Genetics and Genomics (ACMG). We analyzed exome sequencing data from 156 individuals with clinically confirmed IHH/KS. Variants were filtered for P/LP classification using ACMG guidelines across all 84 MAGs in ACMG SF v3.3. Sanger sequencing was used for orthogonal confirmation. The prevalence of MAG variants was compared to external control datasets from the U.K. Biobank (UKB, ~ 50,000 genomes) and the NIH eMERGE Network (~ 21,000 genomes), both based on the ACMG SF v2.0 59-gene list. Among 370,000 variants, 2 individuals (1.3%) carried validated P/LP variants in two distinct MAGs: SCN5A and MYBPC3. Genes 60-84, the additional 25 genes on the ACMG SF v3.3 list, yielded no additional variants. The prevalence of MAG variants in IHH/KS (1.3%) was not significantly different from UKB (2.0%) or eMERGE (2.5%) (OR vs. UKB: OR 0.64; 95% CI, 0.16-2.61; P = 0.57). The frequency of P/LP variants in MAGs among IHH/KS patients is comparable to the general population, suggesting that MAG variants are not common in IHH/KS in contrast to some other types of infertility. Show less

no PDF DOI: 10.1007/s10815-025-03787-w

MYBPC3

Regulatory mechanisms for Snail protein stability: ubiquitin-proteasome system and chaperone-mediated autophagy.

Minju Kim, Keun-Seok Hong, Taeyoung Kim +2 more · 2026 · Experimental & molecular medicine · Nature · added 2026-04-24

Minju Kim, Keun-Seok Hong, Taeyoung Kim, Ki-Jun Ryu, Jiyun Yoo Show less

Snail (SNAI1), a central transcription factor driving epithelial-mesenchymal transition (EMT), is pivotal in cancer metastasis and tissue remodeling. Owing to its labile nature, Snail activity is tigh Show more

Snail (SNAI1), a central transcription factor driving epithelial-mesenchymal transition (EMT), is pivotal in cancer metastasis and tissue remodeling. Owing to its labile nature, Snail activity is tightly controlled by post-translational modifications that dictate its stability. Here this review summarizes how the ubiquitin-proteasome system orchestrates Snail degradation through coordinated phosphorylation and ubiquitination, mediated by diverse E3 ligases and regulated by kinases, acetyltransferases and deubiquitinases. These mechanisms dynamically adjust Snail levels in both the cytoplasm and nucleus, thereby modulating EMT outcomes. In parallel, emerging studies reveal that chaperone-mediated autophagy (CMA) provides an additional layer of regulation. Through recognition of KFERQ-like motifs, CMA selectively directs cytoplasmic Snail to lysosomes for LAMP2A-dependent degradation, functioning as a quality control system. Impairment of CMA leads to nuclear accumulation of Snail, enhancing its EMT-inducing and prometastatic potential. Together, the ubiquitin-proteasome system and CMA represent complementary, context-dependent axes that maintain Snail homeostasis. Their disruption facilitates EMT activation and metastatic progression. By integrating recent findings, this review highlights the dual degradative control of Snail and its implications for cancer biology, providing a conceptual framework for therapeutic approaches aimed at restoring degradative balance and limiting metastasis. Show less

no PDF DOI: 10.1038/s12276-026-01667-6

SNAI1

Elucidating prognostic significance of purine metabolism in colorectal cancer through integrating data from transcriptomic, immunohistochemical, and single-cell RNA sequencing analysis.

Sungyeon Kim, Myunghee Kang, Soyeon Jeong +6 more · 2025 · Molecular oncology · Wiley · added 2026-04-24

Sungyeon Kim, Myunghee Kang, Soyeon Jeong, Jisup Kim, Kyoung Oh Kim, Won-Suk Lee, Jeong-Heum Baek, Jung Ho Kim, Seungyoon Nam Show less

Colorectal cancer (CRC) is widely recognized for its high prevalence and significant mortality rates, and purine metabolism has been serving as a potential therapeutic target. However, purine metaboli Show more

Colorectal cancer (CRC) is widely recognized for its high prevalence and significant mortality rates, and purine metabolism has been serving as a potential therapeutic target. However, purine metabolism has not yet been validated as a prognostic marker through immunohistochemical analysis. In this study, we utilized a combination of bulk transcriptome analysis, immunohistochemistry (IHC), and single-cell RNA sequencing (scRNA-seq) to assess the clinical relevance of purine metabolism in CRC. Low expression levels of five purine metabolism-related genes-ADSL, APRT, ADCY3, NME3, and NME6-were associated with worse prognosis in CRC patient subgroups, including wild-type TP53, mutant TP53, and microsatellite-stable phenotypes. IHC-based validation showed that NME3 expression was an independent prognostic factor, whereas ADSL and NME6 expressions were associated with clinical variables in prediction of prognosis. Notably, NME3 expression predicted a high risk in patients with early-stage CRC, while ADSL and NME6 expressions were predictive in late-stage CRC. scRNA-seq analysis showed that four genes, excluding NME6, had low expression levels in epithelial cells at the late-stage CRC. Despite the reversible nature of purine metabolism reactions, we demonstrated a consistent directional expression of these five prognostic purine metabolism-related proteins in CRC tissues. We suggest that alterations in purine metabolism could serve as a clinically useful prognostic marker in CRC. Show less

📄 PDF DOI: 10.1002/1878-0261.70010

ADCY3

Employment-dependent associations of serum biomarkers with short- and long-term antidepressant treatment outcomes.

Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim +4 more · 2025 · Frontiers in psychiatry · Frontiers · added 2026-04-24

Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim, Min Jhon, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin Show less

This study investigated whether employment status moderates associations between baseline serum biomarkers and antidepressant remission at 12 weeks and 12 months. A prospective cohort of 1086 outpatie Show more

This study investigated whether employment status moderates associations between baseline serum biomarkers and antidepressant remission at 12 weeks and 12 months. A prospective cohort of 1086 outpatients diagnosed with depressive disorders received stepwise antidepressant therapy using a naturalistic, flexible treatment protocol. Fourteen serum biomarkers covering immune (hsCRP, TNF-α, IL-1β, IL-6, IL-4, IL-10), metabolic (leptin, ghrelin, total cholesterol), neuroplastic (BDNF), neurotransmitter (serotonin), endocrine (cortisol), and nutritional (folate, homocysteine) domains were analyzed at baseline. Employment-dependent biomarker associations with remission (Hamilton Depression Rating Scale ≤7) at 12 weeks and 12 months were evaluated using logistic regression with biomarker-by-employment interactions and stratified analyses, adjusting for relevant covariates. Higher serotonin levels significantly predicted 12-week remission exclusively among employed patients, with a significant employment interaction. At 12 months, lower leptin levels predicted remission specifically in employed patients, whereas lower TNF-α and higher BDNF levels predicted remission only in unemployed patients, each demonstrating significant employment interactions. Baseline serum biomarkers showed employment-dependent associations with antidepressant remission outcomes, highlighting serotonin's short-term relevance and leptin, TNF-α, and BDNF as longer-term indicators. Although exploratory, these findings suggest that integrating employment status with biomarker profiles may enhance clinical decision-making by identifying patients who are more or less likely to benefit from treatment across different phases of recovery. Replication in independent cohorts is needed to establish the clinical applicability of such employment-tailored, biomarker-informed strategies. Show less

📄 PDF DOI: 10.3389/fpsyt.2025.1662993

Integrated effects of a 12-week intermittent combined exercise on cognitive function, physical performance, and neurophysiological biomarkers in older women.

Sang-Seo Park, Sang-Hoon Kim, Hye-Sun Yoon +1 more · 2025 · Journal of exercise rehabilitation · added 2026-04-24

Sang-Seo Park, Sang-Hoon Kim, Hye-Sun Yoon, Tae-Woon Kim Show less

Aging is associated with a progressive decline in both cognitive and physical function, and neuroinflammation and metabolic dysregulation often exacerbate this decline, particularly in older women. Th Show more

Aging is associated with a progressive decline in both cognitive and physical function, and neuroinflammation and metabolic dysregulation often exacerbate this decline, particularly in older women. This study investigated the effects of a 12-week intermittent combined exercise program on cognitive function, physical performance, and neurophysiological biomarkers in community-dwelling women aged 75 years and older. Forty participants were recruited from a local welfare center and randomly assigned to an exercise group (n=20) or a control group (n=20). The exercise group participated in three supervised sessions per week that integrated aerobic exercise, resistance exercise, functional exercise, and cognitive exercise. Cognitive domains (attention, language, and memory) were assessed using the Seoul Neuropsychological Screening Test-II. Physical function was assessed using the Geriatric Physical Fitness Test (chair stand, arm flexion, grip strength, and 6-min walk). Blood samples were analyzed to measure serum brain-derived neurotrophic factor (BDNF), interleukin (IL-6), tumor necrosis factor (TNF)-α, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Paired and independent Show less

📄 PDF DOI: 10.12965/jer.2550788.394

Neuroprotective effects of α-lipoic acid on ischemia/reperfusion injury in global cerebral ischemia mouse model.

Soyoung Kwak, Ji Sun Lim, Shin Kim +6 more · 2025 · Scientific reports · Nature · added 2026-04-24

Soyoung Kwak, Ji Sun Lim, Shin Kim, Ye Jin Kwon, Mi-Hee Yu, Mee-Na Park, Dong Kyu Choi, Jeong-Ho Hong, Hae Won Kim Show less

Ischemia-reperfusion (I/R) injury, resulting from transient or permanent cerebral vessel occlusion, triggers oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, leading to p Show more

Ischemia-reperfusion (I/R) injury, resulting from transient or permanent cerebral vessel occlusion, triggers oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, leading to progressive neuronal damage and cognitive decline. The hippocampus, due to its high metabolic demand and susceptibility to oxidative stress, is particularly vulnerable to I/R-induced injury. This study evaluated the neuroprotective effects of α-lipoic acid (α-LA), a potent antioxidant, using bilateral common carotid arteries occlusion/reperfusion (BCCAO/R) mouse model and an oxygen-glucose deprivation/reoxygenation in vitro model. In BCCAO/R mice, α-LA improved spatial memory without affecting motor activity and restored hippocampal tight junction proteins (Claudin-5 and Occludin) and antioxidant enzyme expression, indicating BBB stabilization and oxidative stress reduction. Although synaptic proteins (BDNF and PSD-95) were not restored, cognitive improvements suggest alternative protective mechanisms. In HT22 cells, α-LA decreased intracellular reactive oxygen species levels, enhanced viability, and inhibited apoptosis via decreased PARP cleavage and caspase-3 activation. These protective effects were linked to the activation of the Nrf2/ARE signaling pathway and the upregulation of its downstream antioxidant targets. Overall, α-LA demonstrated marked neuroprotective effects in ischemic models by reducing oxidative stress, preserving BBB integrity, and restoring hippocampal function, positioning it as a promising therapeutic candidate for ischemic brain injury. Show less

📄 PDF DOI: 10.1038/s41598-025-33565-8

Modulation of BDNF/TrkB Signalling Pathway in Alzheimer's Disease: Mechanistic Insights and the Role of Stem Cell Therapy.

Zairin Zulaikha Harun, Auji Abdul Azhar, Yun-Jin Kim +4 more · 2025 · Biomedicines · MDPI · added 2026-04-24

Zairin Zulaikha Harun, Auji Abdul Azhar, Yun-Jin Kim, Farah Wahida Ibrahim, Min-Hwei Ng, Jen-Kit Tan, Yogeswaran Lokanathan Show less

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by the accumulation of amyloid beta (aβ) plaques and neurofibrillary tangles, along with progressive deterioration of Show more

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by the accumulation of amyloid beta (aβ) plaques and neurofibrillary tangles, along with progressive deterioration of cognitive function. AD is the most common form of dementia and affects over 55 million people worldwide. Current treatments for AD are symptomatic-based rather than curative, which calls for the development of new therapeutic strategies. Stem cell therapy has shown promising results for neurodegenerative diseases, including AD. Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), and their downstream signalling cascades play crucial role in modulating neuronal survival, development and synaptic plasticity, which are vital for cognitive functioning, and this pathway is dysregulated in AD. While the BDNF/TrkB signalling pathway dysregulation and stem cell therapy are each widely studied in AD, the interplay between those two remains underexplored. This review focuses on the mechanistic insights of the BDNF/TrkB signalling pathway in normal physiological condition and AD, along with the effects of stem cell therapy on the pathway and its downstream cascades. The findings highlight the therapeutic outcomes in increasing BDNF/TrkB levels and functions, restoring synaptic plasticity, modulating downstream substrates activities and improving cognitive functions. In addition, challenges, limitations and future directions of stem cell therapy are discussed, underscoring the therapeutic benefits of this therapy for AD by modulating the BDNF/TrkB signalling pathway. Show less

📄 PDF DOI: 10.3390/biomedicines13122931

Prognostic impact of endocrine therapy and BDNF-TrkB axis in breast cancer brain metastases.

Joori Kim, Kabsoo Shin, Ahwon Lee +1 more · 2025 · Journal of neuro-oncology · Springer · added 2026-04-24

Joori Kim, Kabsoo Shin, Ahwon Lee, Jieun Lee Show less

We aimed to delineate strategies for improved management of brain metastases (BM) in breast cancer by investigating the estrogen-related BDNF–TrkB pathway within the tumor microenvironment. Surgical s Show more

We aimed to delineate strategies for improved management of brain metastases (BM) in breast cancer by investigating the estrogen-related BDNF–TrkB pathway within the tumor microenvironment. Surgical specimens of BM tissues from breast cancer patients were analyzed using multiplex immunohistochemistry. Expression patterns of BDNF, TrkB, and phospho-AKT were assessed separately in tumor and stromal compartments and compared across molecular subtypes. Clinical data were reviewed to identify factors associated with brain-specific progression-free survival (BPFS) and overall survival (BOS). Endocrine therapy following BM diagnosis was independently associated with prolonged brain-specific survival among luminal patients (HR for BPFS and BOS, 0.22 and 0.19; Survival after BM was influenced by both tumor characteristics and treatment modalities. In luminal disease, endocrine therapy and estrogen depletion may exert anti-tumor activity through inhibition of the BDNF–TrkB pathway. These findings provide novel insight into the biology of breast cancer brain metastases and suggest a rationale for further validation in multicenter studies. Not applicable. The online version contains supplementary material available at 10.1007/s11060-025-05393-3. Show less

📄 PDF DOI: 10.1007/s11060-025-05393-3

Exercise training-induced benefits for Alzheimer's disease are associated with modulation of the BDNF-TrkB signaling complex.

Taewan Kim, Jinkyung Cho, Hyunsik Kang · 2025 · Scientific reports · Nature · added 2026-04-24

The mechanism(s) by which exercise training induces multiple beneficial effects for Alzheimer's disease (AD) patients are not well-understood. This study aimed to examine the link between the brain-de Show more

The mechanism(s) by which exercise training induces multiple beneficial effects for Alzheimer's disease (AD) patients are not well-understood. This study aimed to examine the link between the brain-derived neurotrophic factor (BNDF)-tropomyosin receptor kinase B (TrkB) signaling complex and the beneficial effects of exercise training on cognitive impairment and neuropathology due to AD. At 4 months of age, twenty triple transgenic mice of AD (3x-Tg AD) were randomly assigned to either an AD control (n = 10) or AD exercise (n = 10) group. In parallel, twenty wild-type mice were randomly assigned to either a wild-type control (n = 10) or wild-type exercise (n = 10) group. After 20 weeks of treadmill running, the Morris water maze test was performed, and the mice were then sacrificed for biochemical analyses of plasma and brain tissues. The results indicated that 20 weeks of treadmill running upregulated markers of the BDNF-TrkB signaling complex and mitigated AD neuropathology, along with full recovery from AD-like cognitive impairments. Exercise training also decreased inflammatory cytokines, increased anti-inflammatory cytokines, shifted microglia and astrocytes toward anti-inflammatory phenotypes, improved mitochondrial function, reduced markers of myelin damage, and reduced apoptotic neuronal cell death. In summary, our study findings suggest that exercise training-induced recovery of AD-like cognitive impairments and mitigation of AD neuropathologic biomarkers are associated with modulation of the BDNF-TrkB complex and downstream signaling pathways in 3xTg-AD mice. Show less

📄 PDF DOI: 10.1038/s41598-025-33262-6

Alzheimer-related individual factors modulate effects of transcranial direct current stimulation strength on white matter integrity in mild cognitive impairment.

Jung-Won Lee, Sunghwan Kim, Suhyung Kim +7 more · 2025 · Scientific reports · Nature · added 2026-04-24

Jung-Won Lee, Sunghwan Kim, Suhyung Kim, Yoo Hyun Um, Sheng-Min Wang, TaeYeong Kim, Donghyeon Kim, Hyun Kook Lim, Chang Uk Lee, Dong Woo Kang Show less

Transcranial direct current stimulation (tDCS) is a promising non-invasive intervention for mild cognitive impairment (MCI). This prospective study investigated the relationship between optimized elec Show more

Transcranial direct current stimulation (tDCS) is a promising non-invasive intervention for mild cognitive impairment (MCI). This prospective study investigated the relationship between optimized electrical field (EF) strength of tDCS and white matter (WM) microstructural changes in 55 individuals with MCI. Magnetic resonance imaging (MRI)-based computational modeling was used to optimize EF strength targeting the left dorsolateral prefrontal cortex (DLPFC). Diffusion tensor imaging (DTI) assessed WM integrity through fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Higher EF strength was significantly associated with increased FA and reduced MD and RD in specific left-lateralized tracts, including the anterior thalamic radiation, corticospinal tract, inferior fronto-occipital fasciculus, and inferior longitudinal fasciculus. These EF-dependent WM changes were moderated by Alzheimer's disease (AD)-related factors. Greater WM plasticity was observed in Aβ-positive individuals, APOE ε4 non-carriers, and BDNF Met non-carriers. Moreover, APOE ε4 status significantly moderated the relationship between EF strength and executive function; in non-carriers, stronger EF strength was associated with improved Stroop performance, potentially reflecting enhanced WM integrity in the right superior longitudinal fasciculus. However, no significant associations were observed between EF-sensitive tracts and short-term cognitive changes in the full sample, suggesting that structural modifications may precede functional improvements or require longer follow-up. These findings emphasize the importance of individual AD-related factors in shaping neuromodulatory responses. They also support the need for longitudinal, sham-controlled studies to clarify the clinical implications of EF strength in personalized tDCS for MCI. Show less

📄 PDF DOI: 10.1038/s41598-025-27612-7

Childhood abuse moderates the impact of serum BDNF on short- and long-term antidepressant response.

Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim +4 more · 2025 · European child & adolescent psychiatry · Springer · added 2026-04-24

Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim, Min Jhon, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin Show less

This study aimed to determine whether a history of childhood abuse (CA) and baseline serum brain-derived neurotrophic factor (sBDNF) levels predict remission at 12 weeks and 12 months in patients with Show more

This study aimed to determine whether a history of childhood abuse (CA) and baseline serum brain-derived neurotrophic factor (sBDNF) levels predict remission at 12 weeks and 12 months in patients with depressive disorders, and to examine potential interactions between these factors. A total of 1,086 patients with depressive disorders, participating in a naturalistic, stepwise antidepressant treatment study, were assessed at baseline. CA was evaluated using the Nemesis Childhood Trauma Interview, and sBDNF levels were measured. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. Logistic regression analyses examined the independent and interactive effects of CA and sBDNF on remission outcomes, adjusting for relevant covariates. Low baseline sBDNF independently predicted poorer remission at 12 months (p = 0.045) but not at 12 weeks (p = 0.720). In adjusted analyses, CA alone did not significantly predict remission at either time point (all p > 0.05). However, patients who had both a CA history and low baseline sBDNF showed significantly lower remission rates at 12 weeks (p = 0.018) and 12 months (p = 0.009), indicating a significant interaction between these factors. These findings underscore the importance of integrating psychosocial and biological factors in personalized depression treatment. Routine screening for childhood trauma, combined with assessment of sBDNF levels, may help identify high-risk patients needing targeted interventions. Further prospective research is necessary to validate these findings. Show less

📄 PDF DOI: 10.1007/s00787-025-02944-x

BDNF amyotrophic lateral sclerosis biomarker electrophysiological gold coast criteria motor neuron disease neurodegenerative disease neurology

ALS With and Without Upper Motor Neuron Signs: A Comparative Study Supporting the Gold Coast Criteria.

Hee-Jae Jung, E-Nae Cheong, Jungmin So +5 more · 2025 · Annals of clinical and translational neurology · Wiley · added 2026-04-24

Hee-Jae Jung, E-Nae Cheong, Jungmin So, Heung-Won Kang, Yangsean Choi, Eun-Jae Lee, Hyunjin Kim, Young-Min Lim Show less

The Gold Coast criteria permit diagnosis of amyotrophic lateral sclerosis (ALS) even without upper motor neuron (UMN) signs. However, whether ALS patients with UMN signs (ALSwUMN) and those without (A Show more

The Gold Coast criteria permit diagnosis of amyotrophic lateral sclerosis (ALS) even without upper motor neuron (UMN) signs. However, whether ALS patients with UMN signs (ALSwUMN) and those without (ALSwoUMN) share similar characteristics and prognoses remains unclear. This study compared clinical features, disease progression, electrophysiological findings, biomarker profiles, imaging parameters, and survival between these groups. ALS patients diagnosed according to the Gold Coast criteria were classified into ALSwUMN (n = 51) and ALSwoUMN (n = 20) groups. We evaluated clinical data, motor evoked potentials (MEP), and serum biomarkers, including cardiac Troponin T, neurofilament light chain, glial fibrillary acidic protein, and brain-derived neurotrophic factor. Imaging parameters, including cortical thickness and white matter volume, were also evaluated. Survival was analyzed using the Kaplan-Meier method. The groups showed broadly similar clinical features, disease progression, and biomarker profiles. Abnormal MEPs were more frequent in ALSwUMN (94.0%) than in ALSwoUMN (63.2%, p = 0.017). Both groups demonstrated cortical thinning in the precentral and entorhinal regions compared to healthy controls. ALSwUMN exhibited thinning in the lateral orbitofrontal, insular, and temporal pole regions, while ALSwoUMN showed thinning in the pars opercularis. White matter volume was reduced in both groups in the thalamus, cerebellum, and amygdala, with additional brainstem atrophy in ALSwUMN. No significant survival difference was observed. Despite minor distinctions in electrophysiological and imaging findings, ALSwoUMN had overall comparable clinical profiles and outcomes to ALSwUMN. These findings support recognizing ALSwoUMN within the ALS spectrum under the Gold Coast criteria. Show less

no PDF DOI: 10.1002/acn3.70288

De novo design of miniprotein agonists and antagonists targeting G protein-coupled receptors.

Edin Muratspahić, David Feldman, David E Kim +43 more · 2025 · bioRxiv : the preprint server for biology · Cold Spring Harbor Laboratory · added 2026-04-24

G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development, yet the design of protein agonists and antagonists has been challenging as Show more

G protein-coupled receptors (GPCRs) play key roles in physiology and are central targets for drug discovery and development, yet the design of protein agonists and antagonists has been challenging as GPCRs are integral membrane proteins and conformationally dynamic. Here we describe computational Show less

📄 PDF DOI: 10.1101/2025.03.23.644666

GIPR

Dorsal raphe nucleus MC4R-GABAergic neurons regulate feeding and anxiety.

Satoshi Yamagata, Francesca Copperi, Gavin Thomas White +2 more · 2025 · Molecular metabolism · Elsevier · added 2026-04-24

Satoshi Yamagata, Francesca Copperi, Gavin Thomas White, Jung Dae Kim, Sabrina Diano Show less

The melanocortin receptor 4 (MC4R) plays a key role in the CNS regulation of metabolism. In addition to its role within the hypothalamus, other brain areas, including the dorsal raphe nucleus (DRN), e Show more

The melanocortin receptor 4 (MC4R) plays a key role in the CNS regulation of metabolism. In addition to its role within the hypothalamus, other brain areas, including the dorsal raphe nucleus (DRN), express MC4R. However, the identity and role of these neurons in metabolism regulation are not fully understood. We performed studies to address these questions. We generated Mc4r-cre;Vgat-FlpO and Mc4r-cre;Vglut2-FlpO mice to determine the contribution of these MC4R neuronal populations in DRN. We then chemogenetically activated or inhibited the GABAergic and glutamatergic populations of MC4R. Finally, we selectively deleted MC4R from these two neuronal populations and studied the impact on whole-body metabolism. We found that about 60% of DRN MC4R neurons are GABAergic (Vgat), while only about 20% are glutamatergic (Vglut2). Most of the projections onto DRN neurons originated from the arcuate nucleus (ARC)-POMC neurons, and only a small input from the nucleus of the solitary tract (NTS)-POMC neurons was identified. Significant projections of DRN MC4R/Vgat neurons were observed in the paraventricular nucleus of the hypothalamus (PVN). Chemogenetic activation or inhibition of MC4R/Vgat neurons increased or inhibited food intake, respectively. No effects were observed when the same approach was used in MC4R/Vglut2 neurons. Furthermore, only chemogenetic manipulation of the MC4R/Vgat neurons affected anxiety-like behavior, which was associated with changes in serotonin staining in the DRN. Finally, MC4R-selective deletion in Vgat but not Vglut2 neurons affected whole-body metabolism. These findings suggest that DRN MC4R/Vgat neurons receiving projections from the ARC POMC neurons and projecting to the hypothalamic PVN play a role in metabolism regulation. In addition, this same DRN neuronal subpopulation affects anxiety-like behavior by modulating DRN serotonin neurons. Show less

📄 PDF DOI: 10.1016/j.molmet.2025.102199

Impact of recognition of genetic information related to BMI on changes in physical activity, dietary intake, and blood cholesterol level: a randomized controlled trial.

Ga Young Lee, Junghak Lee, Jeong-Han Kim +2 more · 2025 · European journal of nutrition · Springer · added 2026-04-24

Ga Young Lee, Junghak Lee, Jeong-Han Kim, Kyong-Mee Chung, Sung Nim Han Show less

Genes associated with body mass index (BMI), including FTO rs9939609,MC4R rs17782313, and BDNF rs6265, may influence BMI and regulate energy metabolism. While previous studies have explored health-rel Show more

Genes associated with body mass index (BMI), including FTO rs9939609,MC4R rs17782313, and BDNF rs6265, may influence BMI and regulate energy metabolism. While previous studies have explored health-related behavior changes, few have investigated both biochemical and behavior changes resulting from perceived genetic risk. This study investigated whether recognizing BMI-related genes affects health-related behaviors and alters blood metabolite levels. Normal and overweight adults aged 25-35 years (n = 100) were randomly assigned to an intervention group (n = 65) informed about BMI-related genetic information (FTO rs9939609, MC4R rs17782313, BDNF rs6265) and an uninformed group (n = 35, CON). The intervention group was further divided into Intervention-high risk (IHR, n = 36) and intervention-low risk (ILR, n = 29) subgroups. Dietary intake and physical activity (PA) were assessed using a 3-day dietary record and the IPAQ-short form. Blood metabolites were analyzed through multivariate analyses to identify significant differences among the groups, with measurements taken at baseline, 3 months, and 6 months. The IHR group exhibited increased dietary fat and fast foods intake, along with enhanced vigorous and moderate PA. Six metabolites were selected as biomarkers that were distinguishable among groups, and the relative serum cholesterol levels significantly decreased in the IHR group at 3 months. These results demonstrate that recognizing the BMI-associated genetic risk resulted in a short-term increase in PA but did not improve dietary intake. Increased PA was significantly associated with reduced cholesterol concentration, suggesting the clinical importance of physical activity in the genetically at-risk group. This study was reviewed and approved by the Seoul National University Institutional Review Board (IRB #1901/001-004) and registered on the Clinical Research Information Service (CRIS), KCT0004650 ( https://cris.nih.go.kr/cris/search/detailSearch.do /14091, 2020/01/28). Show less

📄 PDF DOI: 10.1007/s00394-025-03713-x

Distinct Impact of Inflammatory Versus Psychophysiological Stress on Brain-Wide Activation of Melanocortin Receptor 4-Expressing Neurons.

Myunghyun Cheon, Woonhee Kim, ChiHye Chung · 2025 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24

Central melanocortin signaling plays a critical role in maintaining energy homeostasis by regulating energy intake and expenditure, with impairment of this system closely related to metabolic diseases Show more

Central melanocortin signaling plays a critical role in maintaining energy homeostasis by regulating energy intake and expenditure, with impairment of this system closely related to metabolic diseases such as obesity. Among melanocortin receptor subtypes, melanocortin receptor 4 (MC4R) is the primary mediator of these effects within the central nervous system. Accumulating evidence suggests that MC4R contributes to stress-induced disruptions in feeding behavior and energy homeostasis. However, the precise neural mechanisms by which stress alters MC4R activity remain incompletely understood. In this study, we compared brain-wide c-Fos expression patterns induced by two distinct stress paradigms: lipopolysaccharide (LPS)-induced inflammatory stress and restraint stress in male mice, and further examined the involvement of MC4R-expressing (MC4R Show less

📄 PDF DOI: 10.1096/fj.202403158R

Stochastic neuropeptide signals compete to calibrate the rate of satiation.

Stephen X Zhang, Angela Kim, Joseph C Madara +10 more · 2025 · Nature · Nature · added 2026-04-24

Stephen X Zhang, Angela Kim, Joseph C Madara, Paula K Zhu, Lauren F Christenson, Andrew Lutas, Peter N Kalugin, Praneel S Sunkavalli, Yihan Jin, Akash Pal, Lin Tian, Bradford B Lowell, Mark L Andermann Show less

Neuropeptides have important roles in neural plasticity, spiking and behaviour

📄 PDF DOI: 10.1038/s41586-024-08164-8