Korean Journal of Physiology & Pharmacology最新文献

{"title":"Retraction: Polygonatum sibiricum component liquiritigenin restrains breast cancer cell invasion and migration by inhibiting HSP90 and chaperone-mediated autophagy.","authors":"Suli Xu, Zhao Ma, Lihua Xing, Weiqing Cheng","doi":"10.4196/kjpp.24.007rt","DOIUrl":"10.4196/kjpp.24.007rt","url":null,"abstract":"","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathophysiological role of platelet-derived growth factors in chronic liver disease.","authors":"Eun-A Ko, Sung-Cherl Jung, Eun Bok Baek","doi":"10.4196/kjpp.26.125","DOIUrl":"https://doi.org/10.4196/kjpp.26.125","url":null,"abstract":"<p><p>Platelet-derived growth factor (PDGF) and its receptor (PDGFR) signaling serves as a central driver of hepatic stellate cell (HSC) activation and extracellular matrix deposition in chronic liver diseases. Upon ligand binding, PDGFR undergoes dimerization and autophosphorylation, initiating key intracellular signaling pathways including PI3K/Akt, MEK/ERK, <i>PLCγ/IP3</i>, and JAK/STAT. Although these pathways represent major therapeutic targets, the clinical translation of non-selective PDGF inhibitors, such as tyrosine kinase inhibitors, has been hindered by off-target toxicity and limited efficacy. This review delineates the isoform-specific roles of PDGF ligands and receptors in liver fibrosis pathogenesis. We examine this signaling axis across varying disease contexts, ranging from metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD) to end-stage liver disease (ESLD). Furthermore, we discuss the cellular crosstalk among HSCs, Kupffer cells, and endothelial cells within the fibrotic microenvironment. Understanding the signaling mechanisms of PDGF/PDGFR may reveal novel therapeutic targets in chronic liver disease.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of voltage-dependent K⁺ channel activity by the muscarinic receptor antagonist solifenacin in native coronary arterial smooth muscle cells.","authors":"Hye Ryung Kim, Sooa Lee, Seungjoo Kim, Daeun Shin, Seokhun Jeong, Jin Ryeol An, Hongzoo Park, Eun-Taek Han, Jin-Hee Han, Wanjoo Chun, Sunghun Na, Se Jin Lee, Won Sun Park","doi":"10.4196/kjpp.26.211","DOIUrl":"https://doi.org/10.4196/kjpp.26.211","url":null,"abstract":"<p><p>Several muscarinic receptor antagonists have been reported to modulate vascular voltage-dependent K⁺ (Kv) channels; however, the electrophysiological effects of solifenacin on these channels have not been fully characterized. We used the whole-cell patch-clamp technique to examine the effects of solifenacin on Kv currents in rabbit coronary arterial smooth muscle cells. Solifenacin suppressed arterial Kv currents in a concentration-dependent manner, with half-maximal inhibitory concentration (IC₅₀) of 14.59 ± 4.78 μM and a Hill coefficient of 0.84 ± 0.15. Although 30 μM solifenacin did not significantly affect steady-state activation, it produced a pronounced leftward shift in the steady-state inactivation curve. These findings imply that solifenacin inhibits Kv channels through interaction with the inactivation gating machinery. Consistent with this interpretation, solifenacin displayed use (state)-dependent inhibition: repetitive stimulation at 1 Hz progressively reduced current amplitude, and the recovery time constant from inactivation was significantly prolonged. To determine the Kv subtypes involved, subtype-selective inhibitors were applied. The inhibitory effect of solifenacin was not significantly modified by the Kv2.1 inhibitor stromatoxin-1 or the Kv7 inhibitor linopirdine. By contrast, pretreatment with the <i>Kv1.5</i> inhibitor DPO-1 partially attenuated inhibition of peak currents but had minimal effect on steady-state inhibition. These results indicate that solifenacin targets multiple Shaker-related (Kv1.x) channel subtypes, with <i>Kv1.5</i> making a substantial contribution to the observed current suppression. Solifenacin inhibits arterial Kv channels in a concentration- and use (inactivated state)-dependent manner by modulating inactivation gating, predominantly involving the <i>Kv1.5</i> subtype.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 as a danger signal in vascular remodeling.","authors":"Ju Yeon Kim, Hyun Sung, Heejeong Kim, Sun Sik Bae, Chi Dae Kim","doi":"10.4196/kjpp.26.023","DOIUrl":"10.4196/kjpp.26.023","url":null,"abstract":"<p><p>Vascular function is determined by the structural and functional properties of the vascular wall, and accumulating evidence indicates that vascular inflammation is a central pathogenic mechanism underlying a wide spectrum of vascular diseases, including vascular remodeling characterized by structural alterations of the vessel wall. Despite advances in understanding the pathophysiology of vascular remodeling, its biological mechanisms remain complex and incompletely elucidated with respect to both causes and consequences. Emerging evidence supports a critical role for high mobility group box 1 (HMGB1) in the pathogenesis of vascular remodeling. Given its broad range of biological activities and its involvement in key processes of vascular pathology, HMGB1 has gained increasing attention as a potential therapeutic target. This review aims to elucidate the multifaceted role of HMGB1 in vascular remodeling, with particular emphasis on its contributions to vascular inflammation, cellular proliferation and migration, and extracellular matrix remodeling. We provide current mechanistic insights into the molecular signaling pathways activated by HMGB1 in vascular cells and discuss how these pathways contribute to maladaptive vascular remodeling. A deeper understanding of HMGB1-mediated pathways may advance our knowledge of vascular disease pathogenesis and facilitate the development of targeted therapeutic strategies aimed at modulating HMGB1-driven inflammation to prevent or reverse pathological vascular remodeling and its associated complications.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"30 5","pages":"377-393"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148834768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nobiletin in the modified Yiqi Jianpi Decoction enhances the antitumor activity of CD8⁺ T cells in colorectal cancer by regulating the TIMP1/CD274 axis.","authors":"Lan Luo, Fang Zhou, Zheng Liu","doi":"10.4196/kjpp.25.342","DOIUrl":"10.4196/kjpp.25.342","url":null,"abstract":"<p><p>Yiqi Jianpi Decoction (YJD) is a traditional Chinese medicinal formula with reported anticancer properties; however, its effects and regulatory mechanisms in colorectal cancer (CRC) are unclear. Active components and their targets in YJD were identified <i>via</i> the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform, and differentially expressed genes in CRC were extracted from The Cancer Genome Atlas to define the drug-target genes. Potential mechanisms of YJD in CRC were explored through protein-protein interaction network and GO/KEGG enrichment analyses. An <i>in vitro</i> cell model was established: Transwell invasion, wound-healing, and flow-cytometry assays were used to monitor CRC cell viability, while carboxifluorescein diacetate succinimidyl ester assay and lactate dehydrogenase release assay assessed CD8⁺ T-cell activation. TCMSP screening results showed that the compound Nobiletin (NOB) in YJD interacted with the CRC-related gene TIMP1. <i>In vitro</i> experiments demonstrated that TIMP1 expression levels were positively correlated with CD274 and dampened the cytotoxic effect of CD8⁺ T cells against CRC. NOB, by binding to TIMP1, inhibited CD274 expression, enhanced CD8⁺ T-cell activity and proliferation, and thereby boosted their cytotoxic effects on CRC cells. The compound NOB in YJD can enhance the cytotoxicity of CD8⁺ T cells against CRC by targeting the TIMP1/CD274 axis.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"417-429"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome screening and functional validation of FN1 in the regulation of granulosa cell proliferation in polycystic ovary syndrome.","authors":"Kan Zhou, Wenquan Han, Qijie Wang, Yu Zhang, Jiao Wang","doi":"10.4196/kjpp.25.418","DOIUrl":"10.4196/kjpp.25.418","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) affects 11%-13% of reproductive-age women worldwide and is pathologically associated with granulosa cell dysfunction. This study employed transcriptome sequencing of granulosa cells from PCOS patients and non-PCOS controls, followed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Key differentially expressed genes were validated by quantitative real-time PCR. Transcriptome analysis identified 157 upregulated and 71 downregulated mRNAs in PCOS granulosa cells, with enrichment in PI3K-Akt, MAPK, and TGF-beta signaling pathways. Six genes-NPTX2, FN1, CCN1, IDH1, ZCCHC17, and CREG1-were confirmed by qRT-PCR. Protein-protein interaction network analysis identified FN1 as a central hub gene. FN1 knockdown in KGN cells suppressed proliferation, induced apoptosis, and caused G1 phase arrest, accompanied by reduced Akt phosphorylation and altered expression of cyclin D1, p21, and p27. These findings suggest a potential association between FN1 and granulosa cell proliferative dysregulation in PCOS, warranting validation in primary cells and <i>in vivo</i> models.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"469-485"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147789518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual role of homocysteine in enhancing metabolic activity and suppressing inflammatory cytokines in murine immune cells.","authors":"Thi Len Ho, Eun-Ju Ko","doi":"10.4196/kjpp.26.005","DOIUrl":"10.4196/kjpp.26.005","url":null,"abstract":"<p><p>Homocysteine (HCy) is a sulfur-containing metabolic intermediate with largely unexplored potential as a damage-associated molecular pattern. This study investigated the immunomodulatory profile of HCy alone and in combination with the TLR4 agonist monophosphoryl lipid A (MPL). To model acute metabolic stress, we evaluated murine bone marrow-derived dendritic cells (DCs), macrophages, and splenocytes treated with HCy (6.25-600 μg/ml) <i>in vitro</i>, and assessed inflammatory cell recruitment <i>in vivo</i> in mice injected intraperitoneally with HCy (100 or 500 μg/mouse). HCy treatment significantly increased mitochondrial metabolic activity (CCK-8) without generalized necrosis. However, high concentrations (400-600 μg/ml) paradoxically suppressed MPL-induced splenocyte proliferation. HCy displayed distinct cell-specificity, acting as a direct agonist for macrophage maturation (upregulating CD40, CD86, and MHC-II) while failing to activate purified DCs. Notably, flow cytometry revealed that while metabolic signals increased, high-dose HCy induced late apoptosis in macrophages starting at 25 μg/ml, suggesting a state of metabolic stress rather than enhanced viability. Crucially, HCy exerted a regulatory effect on TLR4 signaling: co-treatment with HCy (200-600 μg/ml) dose-dependently suppressed MPL-induced pro-inflammatory cytokine secretion (TNF-α, IL-6) while maintaining phenotypic maturation. <i>In vivo</i>, HCy functioned as a chemotactic agent, recruiting DCs and monocytes to the peritoneal cavity and inducing an activated, M2-like (CD206⁺) macrophage phenotype. These findings demonstrate that HCy functions as a dual-action immune modulator that promotes phenotypic maturation and antigen-presenting cell recruitment while dampening excessive cytokine release through a stress-mediated regulatory mechanism.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"457-467"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal microbiota transplantation alleviates sepsis-induced acute lung injury by improving mitochondrial function.","authors":"Mei-Tong Wang, Dan Wang, Yu-Peng Qi, Qun Chen, Xue-Mei Qin, Tong Wang, Wei-Hua Lu, Ying-Ya Cao","doi":"10.4196/kjpp.25.304","DOIUrl":"10.4196/kjpp.25.304","url":null,"abstract":"<p><p>Sepsis-induced acute lung injury (ALI) remains a critical clinical challenge with limited therapeutic options. This study investigated the protective effects and underlying mechanisms of fecal microbiota transplantation (FMT) in a murine model of sepsis-induced ALI. 16S rRNA sequencing confirmed that FMT rescued sepsis-induced gut microbiota dysbiosis, restoring microbial diversity and composition. The results demonstrated that FMT significantly improved survival, attenuated pulmonary pathological damage and edema, and reduced systemic and pulmonary levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). Furthermore, FMT preserved alveolar-capillary barrier integrity, as evidenced by reduced vascular permeability and upregulated expression levels of tight junction proteins (ZO-1 and occludin). Mechanistically, FMT ameliorated mitochondrial dysfunction in lung tissue, as evidenced by the restoration of oxidative phosphorylation capacity, increased ATP production, reduced mitochondrial reactive oxygen species accumulation, and decreased mitochondrial DNA release. These improvements were associated with a rebalancing of mitochondrial dynamics, characterized by increased expression levels of fusion proteins (OPA1, Mfn1, and Mfn2) and decreased expression of a fission protein (Drp1). Our findings highlight the gut-lung axis as a therapeutic target in sepsis and demonstrate that FMT alleviates sepsis-induced ALI by restoring gut microbiota homeostasis and subsequently preserving mitochondrial function. Further clinical studies are warranted to validate these preclinical findings and explore optimal FMT protocols for critical care applications.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"395-405"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteogenic, antiresorptive, and toxicological evaluation of alpha-mangostin in MC3T3-E1 cells and medaka fish.","authors":"Ut Dong Thach, Huy Manh Nguyen, Van Oanh Nguyen, Chau Phi Dinh, Thi Thuy Trang Le, Thi Ngoc Tram Le, Ngoc Mai Do, Thi Nhung Duong, Thi Bich Pham, Duc Long Tran, Thanh Thuy To","doi":"10.4196/kjpp.25.370","DOIUrl":"10.4196/kjpp.25.370","url":null,"abstract":"<p><p>Osteoporosis, characterized by excessive bone resorption, requires new therapeutic agents with high efficacy and favorable safety profiles. In this study, we isolated alpha-mangostin (aMG) from the peel of <i>Garcinia mangostana</i> L. and investigated its osteogenic, antiresorptive, and toxicological activities. The osteogenic effects were evaluated <i>in vitro</i> using MC3T3-E1 pre-osteoblast cells, whereas acute toxicity and bone-protective activity were assessed <i>in vivo</i> using medaka fish (<i>Oryzias latipes</i>) . In MC3T3-E1 cells, aMG promoted osteogenic differentiation by enhancing proliferation, alkaline phosphatase activity, collagen synthesis, and mineralization at 1 and 10 μM, whereas cytotoxicity was observed at 100 and 1,000 μM. In medaka embryos and larvae, aMG induced acute toxicity with LC₅₀ values (concentrations causing 50% mortality) of 91.27 and 3.44 μM, and EC₅₀ values (concentrations causing 50% of developmental abnormalities) of 103.66 and 3.3 μM, respectively, leading to tail deformities, hemorrhage, and reduced hatching and heart rates. At sub-toxic concentrations (0.25-1 μM), aMG significantly attenuated Rankl-induced bone loss in the neural arches of osteoporotic medaka larvae. Collectively, this study provides the first evidence of the dual osteogenic and antiresorptive actions of aMG, along with its toxicity profile, highlighting its potential as a plant-derived anti-osteoporosis agent.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"445-456"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binaphthoquinone attenuates myofibroblast transition of human ventricular cardiac fibroblasts <i>in vitro via</i> mitochondrial modulation under diabetic conditions.","authors":"Chang Shin Yoon, Jeong Rim Ko, Nammi Park, Se Hwan Park, Hyoung Kyu Kim, Jin Han","doi":"10.4196/kjpp.25.434","DOIUrl":"10.4196/kjpp.25.434","url":null,"abstract":"<p><p>Binaphthoquinone (BiNQ), a dimeric compound composed of juglone (5-hydroxy-1,4-naphthoquinone) and naphthazarin (5,8-dihydroxy-1,4-naphthoquinone), was originally isolated from the sea urchin <i>Spatangus purpureus</i> O.F. Müller. In this study, we examined the anti-fibrotic effects of BiNQ in a diabetic context, focusing on its potential to enhance mitochondrial function. Human cardiac fibroblasts (NHCF-V) were cultured under control 5 mM glucose or exposed to 33 mM glucose plus palmitic acid (100 μM). Fibroblast-to-myofibroblast transition was evaluated by measuring the expression level of the myofibroblast marker α-smooth muscle actin (α-SMA), and functional changes were further assessed using a contraction assay. BiNQ was applied at two concentrations (10 nM and 1 μM) and was found to reduce α-SMA expression, indicating inhibition of myofibroblast differentiation. Concurrently, BiNQ enhanced the expression of mitochondrial respiratory chain complexes, resulting in increased ATP production. To elucidate the underlying molecular mechanisms, targeted proteomic analysis was performed using LC-MS/MS, enabling identification and quantification of proteins involved in mitochondrial bioenergetics and fibrotic regulation. Collectively, these findings suggest that BiNQ attenuates fibroblast activation in a diabetic context by improving mitochondrial function and modulating key pro-fibrotic pathways.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"407-416"},"PeriodicalIF":2.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147977389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}