Biomolecules & Therapeutics最新文献_第4页

Application of Caenorhabditis elegans' Feeding Behavior-Based Assay in Drug Discovery and Development. 基于秀丽隐杆线虫摄食行为测定在药物研发中的应用。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-07-01 Epub Date: 2026-06-30 DOI: 10.4062/biomolther.2025.250

Aaron Taehwan Kim, Yeonhwa Park

引用次数: 0

Molecular Pathogenesis of Vitiligo: Emerging Roles of Epigenetic Regulation. 白癜风的分子发病机制：表观遗传调控的新作用。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-07-01 Epub Date: 2026-06-30 DOI: 10.4062/biomolther.2026.037

Hye-Jin Ahn, Mi Kyung Park, Ki-Heon Jeong

{"title":"Molecular Pathogenesis of Vitiligo: Emerging Roles of Epigenetic Regulation.","authors":"Hye-Jin Ahn, Mi Kyung Park, Ki-Heon Jeong","doi":"10.4062/biomolther.2026.037","DOIUrl":"10.4062/biomolther.2026.037","url":null,"abstract":"Vitiligo is a chronic acquired depigmenting disorder characterized by progressive loss of functional melanocytes and is commonly associated with other autoimmune diseases. Although genome-wide association studies have identified multiple susceptibility loci, incomplete concordance among monozygotic twins and variable onset indicate strong contributions from environmental triggers and gene-environment interactions. A convergent pathogenic sequence is emerging: oxidative stress and defective cytoprotective responses render melanocytes vulnerable, promote release of danger signals, and activate innate immune pathways, followed by adaptive cytotoxic immunity dominated by autoreactive CD8+ T cells. Keratinocyte,fibroblasts immune crosstalk driven by IFN-γ and downstream JAK-STAT signaling induces CXCL9/CXCL10, recruiting CXCR3+ T cells and sustaining an amplification loop; CXCL10-CXCR3B signaling may also directly enhance melanocyte apoptosis. Tissue-resident memory T cells further maintain local immune surveillance and contribute to relapse after therapy. Epigenetic regulation provides a mechanistic bridge that translates transient stress into durable transcriptional states in both cutaneous cells and immune compartments. We review evidence for altered DNA methylation at melanocyte differentiation and survival genes (e.g., TYR, MITF) and immune regulatory loci (e.g., NLRP1, PTPN22), as well as contributions from histone modifications and non-coding RNAs that shape cytokine production and checkpoint pathways. Finally, we discuss translational opportunities, including topical JAK inhibition, epigenetic biomarkers for prognosis and treatment response, and emerging strategies for targeted epigenetic modulation. Integrated epigenomic approaches have the potential to advance the development of next-generation therapies.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"818-829"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erastin-Induced Ferroptosis Overcomes Oxaliplatin Resistance in Colorectal Cancer Cells. erastin诱导的铁下垂克服了大肠癌细胞对奥沙利铂的耐药性。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-07-01 Epub Date: 2026-06-30 DOI: 10.4062/biomolther.2026.038

Na Yeong Lee, Sang Hoon Joo, Si Yeong Seo, Seung-On Lee, Goo Yoon, Jin Woo Park, Jung-Hyun Shim

{"title":"Erastin-Induced Ferroptosis Overcomes Oxaliplatin Resistance in Colorectal Cancer Cells.","authors":"Na Yeong Lee, Sang Hoon Joo, Si Yeong Seo, Seung-On Lee, Goo Yoon, Jin Woo Park, Jung-Hyun Shim","doi":"10.4062/biomolther.2026.038","DOIUrl":"10.4062/biomolther.2026.038","url":null,"abstract":"Chemotherapy resistance remains a significant obstacle in the treatment of colorectal cancer (CRC) patients. Here, we examined the ferroptosis susceptibility of the chemotherapy-resistant CRC cell line HCT116-OxR relative to its parental counterpart. The increased basal levels of reactive oxygen species (ROS) and ferroptosis-associated proteins observed in HCT116-OxR cells rendered them more sensitive to erastin-induced cell death, as determined by the MTT and soft agar assays. Mechanistically, erastin elicited a reduction in mitochondrial membrane potential (MMP). Notably, this loss of MMP was not accompanied by detectable apoptotic changes, suggesting that a non-apoptotic cell death pathway may be involved. Rather, erastin elevated intracellular iron and ROS concentrations, resulting in lipid peroxidation consistent with ferroptosis. The pivotal involvement of ROS was supported by N-Acetyl-L-cysteine pretreatment, and ferrostatin-1 pretreatment further verified that erastin-induced cell death was mediated by ferroptosis. The heightened erastin sensitivity of HCT116-OxR cells suggests a therapeutic vulnerability that could be exploited to induce ferroptosis in chemotherapy-resistant CRC. This ferroptosis susceptibility may offer a promising strategy for overcoming treatment resistance and improving therapeutic outcomes.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 4","pages":"891-900"},"PeriodicalIF":4.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum Starvation Promotes the Proteolysis of OGT by Activating AMPK and the CUL1/SKP1/SKP2 E3 Ubiquitin Ligase in 3T3-L1 Cells. 在3T3-L1细胞中，血清饥饿通过激活AMPK和CUL1/SKP1/SKP2 E3泛素连接酶促进OGT的蛋白水解。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-06-30 Epub Date: 2026-06-05 DOI: 10.4062/biomolther.2026.052

Hoang Hai Ngo, Dang Quynh Le, Le Ba Nam, Young-Sam Keum

{"title":"Serum Starvation Promotes the Proteolysis of OGT by Activating AMPK and the CUL1/SKP1/SKP2 E3 Ubiquitin Ligase in 3T3-L1 Cells.","authors":"Hoang Hai Ngo, Dang Quynh Le, Le Ba Nam, Young-Sam Keum","doi":"10.4062/biomolther.2026.052","DOIUrl":"10.4062/biomolther.2026.052","url":null,"abstract":"Post-translational modifications (PTMs) play a crucial role in the regulation of protein function. Protein O-linked N-acetylglucosamine (O-GlcNAc) is a type of nutrient-sensitive PTM that occurs on serine or threonine residues of substrates, catalysed by single pair of enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). In the present study, we have observed that serum deprivation decreased OGT levels without affecting its transcription. Instead, we found that serum deprivation activated AMP-activated protein kinase (AMPK) and induced the phosphorylation of OGT at threonine 444, resulting in the proteolysis of OGT by the CUL1/SKP1/SKP2 E3 ubiquitin ligase. Knocking down OGT significantly impaired 3T3-L1 cell differentiation in the presence of serum. Likewise, treatment with AICAR, an AMPK activator, or OSMI-1, an OGT small molecule inhibitor, attenuated serum-induced 3T3-L1 differentiation. Together, our results demonstrate that OGT is essential for 3T3 cell differentiation in which serum starvation activates AMPK to phosphorylate OGT at Thr444, triggering the proteolysis of OGT by the CUL1/SKP1/SKP2 E3 ligase.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"910-921"},"PeriodicalIF":4.9,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Erratum to "Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas with CDK4-Amplification" [Biomol Ther 34(2), 379-390 (2026)]. “利用cdk4扩增鉴定复杂核型软组织肉瘤生物标志物候选物的生物信息学分析”[生物医学杂志]34(2),379-390（2026）。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.007

Eun-Young Lee, Hyun Sang Cho, June Hyuk Kim, Hyun Guy Kang, Jong Woong Park, Ahyoung Cho, Hye Jin You

引用次数: 0

Erratum to "Molecular Mechanisms Underlying the Anti-Cancer Effects of Tangeretin, a Phytochemical from Citrus Extracts" [Biomol Ther 34(2), 279-290 (2026)]. “柑桔皮苷抗癌作用的分子机制”[j].中国生物医学工程学报，34(2),279-290（2026）。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.002

Seung-Hyeon Ahn, Kyung-Chul Choi

引用次数: 0

Stress Accelerates Depressive-Like Behaviors through Increase of Notch2 Expression in N141I Mutation Presenilin-2 Transgenic Mice. 在N141I突变早老素-2转基因小鼠中，应激通过增加Notch2表达加速抑郁样行为。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2025.246

Seung Sik Yoo, Sun Mi Gu, Kyung Tak Nam, Jeong Soon Choi, Yong Sun Lee, In Jun Yeo, Ji Eun Yu, Sanghyeon Kim, Dong Won Lee, Hyeon Joo Ham, Ju Young Chang, Jaesuk Yun, Dong Ju Son, Sang-Bae Han, Jin Tae Hong

{"title":"Stress Accelerates Depressive-Like Behaviors through Increase of Notch2 Expression in N141I Mutation Presenilin-2 Transgenic Mice.","authors":"Seung Sik Yoo, Sun Mi Gu, Kyung Tak Nam, Jeong Soon Choi, Yong Sun Lee, In Jun Yeo, Ji Eun Yu, Sanghyeon Kim, Dong Won Lee, Hyeon Joo Ham, Ju Young Chang, Jaesuk Yun, Dong Ju Son, Sang-Bae Han, Jin Tae Hong","doi":"10.4062/biomolther.2025.246","DOIUrl":"10.4062/biomolther.2025.246","url":null,"abstract":"Alzheimer's disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depression-like behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer's disease and depression. Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"544-555"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Licochalcone E Ameliorates Hepatic Steatosis in Obese Mice by Activating the Sirt1/AMPK Pathway and Reducing Hepatic Lipid Accumulation. 甘草查尔酮E通过激活Sirt1/AMPK通路和减少肝脏脂质积累改善肥胖小鼠肝脏脂肪变性

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2025.162

Wen-Chung Huang, Shu-Ju Wu, Xuan-Min Liu, Shu-Chen Cheng, Po-Ting Lin, Chun-Ling Kuo, Chian-Jiun Liou

{"title":"Licochalcone E Ameliorates Hepatic Steatosis in Obese Mice by Activating the Sirt1/AMPK Pathway and Reducing Hepatic Lipid Accumulation.","authors":"Wen-Chung Huang, Shu-Ju Wu, Xuan-Min Liu, Shu-Chen Cheng, Po-Ting Lin, Chun-Ling Kuo, Chian-Jiun Liou","doi":"10.4062/biomolther.2025.162","DOIUrl":"10.4062/biomolther.2025.162","url":null,"abstract":"Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid-induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"676-688"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunomodulatory Effects of Human Breast Milk-Derived Exosomes on Myeloid Cells and Chondrocytes. 人母乳来源的外泌体对骨髓细胞和软骨细胞的免疫调节作用。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2025.229

Dahyeon Kwon, Ji Yoon Yoo, Kang-Bin Dan, Ki-Uk Kim, Ji-Yun Lee, Hyeyoung Min

{"title":"Immunomodulatory Effects of Human Breast Milk-Derived Exosomes on Myeloid Cells and Chondrocytes.","authors":"Dahyeon Kwon, Ji Yoon Yoo, Kang-Bin Dan, Ki-Uk Kim, Ji-Yun Lee, Hyeyoung Min","doi":"10.4062/biomolther.2025.229","DOIUrl":"10.4062/biomolther.2025.229","url":null,"abstract":"Human breast milk (HBM) is an ideal nutritional source for the growth and development of infants. In addition, HBM contains hormones, growth factors, microRNAs and exosomes that perform various physiological functions. This study investigates the immunomodulatory effects of HBM-derived exosomes on myeloid cells and chondrocytes, and implications for juvenile idiopathic arthritis. HBM-derived exosomes were isolated and characterized using nanoparticle track analyzer and Western blotting. The HBM-derived exosomes treatment decreased the expression of inflammatory mediators and proinflammatory cytokines in mouse peritoneal macrophages upon lipopolysaccharide stimulation. Flow cytometry analysis of bone marrow-derived macrophages indicated that exosomes promoted M2 polarization, as evidenced by a decrease in cells expressing CD80 (M1 marker) and a concurrent increase in cells expressing M2 marker CD206. In addition, exosome treatment attenuated the mitogen-activated protein kinase signaling pathway by reducing the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and IκB-α, thereby reducing the expression of inducible nitric oxide synthase, cyclooxygenase-2, metalloprotease (MMP)-1, MMP-3, and MMP-13 in SW1353 chondrocytes following IL-1β stimulation. These findings suggest that HBM-derived exosomes promote macrophage polarization toward an anti-inflammatory M2 phenotype and exert significant immunomodulatory effects.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"689-696"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Anti-Fibrotic Role of G-Protein-Coupled Receptor 119 in Hepatic Stellate Cells. g蛋白偶联受体119在肝星状细胞中的抗纤维化作用。

IF 4.9 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.064

Jeongwoo Park, Min Hoo Lee, Hyun Young Kim, Hyo Seon Kim, Sang Kyum Kim, Jin Won Yang, Keon Wook Kang

{"title":"A Novel Anti-Fibrotic Role of G-Protein-Coupled Receptor 119 in Hepatic Stellate Cells.","authors":"Jeongwoo Park, Min Hoo Lee, Hyun Young Kim, Hyo Seon Kim, Sang Kyum Kim, Jin Won Yang, Keon Wook Kang","doi":"10.4062/biomolther.2026.064","DOIUrl":"10.4062/biomolther.2026.064","url":null,"abstract":"Liver fibrosis arises from chronic hepatic injury and remains a major clinical challenge due to the lack of effective therapies. Although G-protein-coupled receptor 119 (GPR119) has been explored as a metabolic target in type 2 diabetes, its role in liver fibrogenesis is not well understood. In this study, the protein and mRNA expression of GPR119 were detected in mouse primary hepatic stellate cells (HSCs) using immunostaining and reverse transcriptase-polymerase chain reaction. The anti-fibrotic activities of GPR119 agonists were assessed in primary HSCs, LX-2 cells, and a carbon tetrachloride (CCl₄)-induced mouse model of liver fibrosis. Treatment with the GPR119 agonists MBX-2982 and GSK1292263 inhibited HSC activation, suppressed transforming growth factor-β1 (TGFβ1)-induced Smad2/3 phosphorylation, and reduced the expression of fibrogenic genes. In vivo, oral administration of MBX-2982 attenuated collagen accumulation and decreased hepatic α-smooth muscle actin and TGFβ expression in CCl₄-treated mice. Mechanistically, MBX-2982 activated AMP-activated protein kinase (AMPK), and pharmacological inhibition of AMPK reversed its anti-fibrogenic effects. MBX-2982 further reduced Smad3 acetylation by disrupting the interaction between Smad3 and p300 and promoting AMPK-dependent proteasomal degradation of p300. These results identify GPR119 as a regulator of HSC activation and highlight GPR119 agonists as promising therapeutic candidates for liver fibrosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"666-675"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0