Korean Journal of Physiology & Pharmacology最新文献

Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells.

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-07 DOI: 10.4196/kjpp.24.273

Hao Jin, Yu Ran Lee, Sungmin Kim, Eun-Ok Lee, Hee Kyoung Joo, Heon Jong Yoo, Cuk-Seong Kim, Byeong Hwa Jeon

{"title":"Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells.","authors":"Hao Jin, Yu Ran Lee, Sungmin Kim, Eun-Ok Lee, Hee Kyoung Joo, Heon Jong Yoo, Cuk-Seong Kim, Byeong Hwa Jeon","doi":"10.4196/kjpp.24.273","DOIUrl":"https://doi.org/10.4196/kjpp.24.273","url":null,"abstract":"The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3. The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574687","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}

引用次数: 0

Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma. 透明质酸介导的运动受体介导的有氧糖酵解增强了肺腺癌的干样特性和化疗耐药性。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-07 DOI: 10.4196/kjpp.24.275

Wenwen Yu, Yubo Shi, Xiaoqiong Bao, Xiangxiang Chen, Yangyang Ni, Jincong Wang, Hua Ye

{"title":"Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma.","authors":"Wenwen Yu, Yubo Shi, Xiaoqiong Bao, Xiangxiang Chen, Yangyang Ni, Jincong Wang, Hua Ye","doi":"10.4196/kjpp.24.275","DOIUrl":"https://doi.org/10.4196/kjpp.24.275","url":null,"abstract":"Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574618","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}

引用次数: 0

Roles of PDGF/PDGFR signaling in various organs. PDGF/PDGFR 信号在不同器官中的作用。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-10-31 DOI: 10.4196/kjpp.24.309

Sung-Cherl Jung, Dawon Kang, Eun-A Ko

{"title":"Roles of PDGF/PDGFR signaling in various organs.","authors":"Sung-Cherl Jung, Dawon Kang, Eun-A Ko","doi":"10.4196/kjpp.24.309","DOIUrl":"10.4196/kjpp.24.309","url":null,"abstract":"Platelet-derived growth factors (PDGFs) ligands and their corresponding receptors, PDGF receptor (PDGFR)α and PDGFRβ, play a crucial role in controlling diverse biological functions, including cell growth, viability and migration. These growth factors bind to PDGFRs, which are receptor tyrosine kinases present on the surface of target cells. The interaction between PDGFs and PDGFRs induces receptor dimerization and subsequent activation through auto-phosphorylation, which in turn triggers a cascade of intracellular signaling pathways. PDGF/PDGFR signaling is essential for maintaining normal physiological functions, including tissue regeneration and growth. However, dysregulation of this signaling pathway leads to pathological conditions, including fibrosis, atherosclerosis, and cancer development in various organs. The pathological impact of PDGF/PDGFR signaling primarily stems from its capacity to promote excessive cell proliferation, enhanced migration, and increased extracellular matrix deposition, resulting in tissue overgrowth, scarring, and abnormal vessel formation. These processes are integral to the pathogenesis of fibrotic, neoplastic, and vascular disorders. Therefore, understanding these pathways is crucial for developing targeted treatments designed to inhibit PDGF/PDGFR signaling in these diseases. This review delves into the dual role of PDGF/PDGFR signaling in both physiological and pathophysiological contexts across different organs and provides insights into current pharmacological therapies designed to target the PDGF signaling pathway.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"139-155"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559476","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}

引用次数: 0

Protective effect of maltol on pathological response of cardiomyocyte in dystrophic mice. 麦芽酚对营养不良小鼠心肌细胞病理反应的保护作用

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.246

Ahyoung Lee, Hayeong Kwon, Seulmin Kim, Yoonhee Jeong, Byung Tae Choi, Changwon Kho

{"title":"Protective effect of maltol on pathological response of cardiomyocyte in dystrophic mice.","authors":"Ahyoung Lee, Hayeong Kwon, Seulmin Kim, Yoonhee Jeong, Byung Tae Choi, Changwon Kho","doi":"10.4196/kjpp.24.246","DOIUrl":"10.4196/kjpp.24.246","url":null,"abstract":"Heart diseases are a significant contributor to global morbidity and mortality, and despite their diverse and complex mechanisms, treatment options remain limited. Maltol, a natural compound with antioxidant and anti-inflammatory activities, exhibits potential for addressing this need. This study evaluates the cardioprotective effects of maltol in isoproterenol (ISO)-induced cardiac stress models and Duchenne muscular dystrophy (DMD). Maltol's cardiac cytotoxicity was assessed in rodent (H9c2) and human (AC16) cells and compared with that of dapagliflozin to illustrate its cardiac safety. In ISO-induced stress models, maltol significantly reduced hypertrophic markers and inflammation while enhancing autophagy and antioxidant pathways. In the mdx mice, a DMD model, maltol treatment improved cardiac contractility and reduced pathogenic remodeling. Enhanced phosphorylation of phospholamban and trends toward higher SERCA2a expression indicated enhanced Ca2+ handling, which is crucial in DMD cardiomyopathy. This study demonstrated that maltol has the potential to provide therapeutic benefits for DMD and other cardiac conditions characterized by hypertrophy and inflammation, as evidenced by its well-known antioxidant properties, low cytotoxicity, and capacity to enhance cardiac function and Ca2+ handling.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"235-244"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632827","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}

引用次数: 0

Neurosteroids and neurological disorders. 神经类固醇和神经紊乱。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2025-01-14 DOI: 10.4196/kjpp.24.353

Gi Wan Park, Hayoung Kim, Seong Hyun Won, Nam Hyun Kim, Sheu-Ran Choi

{"title":"Neurosteroids and neurological disorders.","authors":"Gi Wan Park, Hayoung Kim, Seong Hyun Won, Nam Hyun Kim, Sheu-Ran Choi","doi":"10.4196/kjpp.24.353","DOIUrl":"10.4196/kjpp.24.353","url":null,"abstract":"Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl- D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors. In addition, numerous neurological disorders, including persistent neuropathic pain, multiple sclerosis, and seizures, have altered the levels of neurosteroids in the central nervous system. Thus, we review how local synthesis and metabolism of neurosteroids are modulated in the central nervous system and describe the role of neurosteroids under pathological conditions. Furthermore, we discuss whether neurosteroids may play a role as a new therapeutic for the treatment of neurological disorders.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"157-164"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980697","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}

引用次数: 0

Oligomeric proanthocyanidin ameliorates sepsis-associated renal tubular injury: involvement of oxidative stress, inflammation, PI3K/AKT and NFκB signaling pathways. 低聚原花青素可改善败血症相关的肾小管损伤：氧化应激、炎症、PI3K/AKT 和 NFκB 信号通路的参与。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.121

Enhui Cui, Qijing Wu, Haiyan Zhu, Weiqian Tian

{"title":"Oligomeric proanthocyanidin ameliorates sepsis-associated renal tubular injury: involvement of oxidative stress, inflammation, PI3K/AKT and NFκB signaling pathways.","authors":"Enhui Cui, Qijing Wu, Haiyan Zhu, Weiqian Tian","doi":"10.4196/kjpp.24.121","DOIUrl":"10.4196/kjpp.24.121","url":null,"abstract":"Sepsis is a potentially fatal infectious disease that easily causes shock and numerous organ failures. The kidney is one of the most susceptible to injury. Early intervention and renal protection significantly minimize patient mortality. Oligomeric proanthocyanidin (OPC), a naturally occurring plant compound, has a high potential for renal protection. This study was aimed at exploring the potential renoprotective role of OPC in sepsis-related renal tubular injury. C57/B6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to simulate sepsis-related acute kidney injury in vivo. Renal function and pathology were assessed. RNA sequencing examined OPC mechanisms against LPS-induced renal injury. Oxidative stress indicators and inflammatory cytokines in blood serum and renal tissues were evaluated. In vitro, MTT assays assess cell viability. Apoptosis cells were detected using Hoechst 33342 and propidium iodide staining. Western blot assessed PI3K/AKT and NFκB signaling pathway proteins. OPC reduced LPS-induced renal tubular injury, improved renal functions and pathological changes, restored glutathione content, superoxide dismutase activity, and catalase activity, inhibited malondialdehyde overproduction, and suppressed LPS-induced overproduction of pro-inflammatory cytokines and the decline of anti-inflammatory cytokines. OPC attenuated LPS-induced cell morphological injury, reduced cell viability loss, and recovered the changes in proteins involved in PI3K/AKT and NFκB signaling pathways in MTEC cells. OPC protects against LPSinduced renal tubular injury by counteracting oxidative stress, inhibiting inflammatory responses, activating the PI3K/AKT signaling pathway, and inhibiting the NFκB signaling pathway. It may provide a viable solution to lessen renal injury in patients with sepsis.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"165-178"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632825","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}

引用次数: 0

The impact of CYP2D6 on donepezil concentration and its lack of effect on the treatment response and adverse effect in Korean patients with Alzheimer's disease. 韩国阿尔茨海默病患者 CYP2D6 对多奈哌齐浓度的影响及其对治疗反应和不良反应的影响。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.239

Tae-Eun Kim, Jung-Woo Bae, Seongkuk Hong, Hong Jun Jeon, Yeonsil Moon

{"title":"The impact of CYP2D6 on donepezil concentration and its lack of effect on the treatment response and adverse effect in Korean patients with Alzheimer's disease.","authors":"Tae-Eun Kim, Jung-Woo Bae, Seongkuk Hong, Hong Jun Jeon, Yeonsil Moon","doi":"10.4196/kjpp.24.239","DOIUrl":"10.4196/kjpp.24.239","url":null,"abstract":"Donepezil, an acetylcholinesterase inhibitor, is widely used for managing the symptoms of Alzheimer's disease (AD), yet its clinical response varies widely among individuals. This study aims to investigate the influence of CYP2D6 genetic variants on donepezil concentration, treatment response, and adverse effects in Korean patients with AD dementia. We conducted a longitudinal study involving 76 patients receiving either 5 mg or 10 mg of donepezil. Genetic testing identified 9 CYP2D6 alleles, categorizing patients by metabolizing abilities. Blood sampling for plasma concentrations of donepezil were performed at steady-state. Mini-Mental State Examination (MMSE) were conducted at 12, 24 and 36 months after the initiation of treatment. Adverse events were collected throughout the study period. Donepezil plasma concentrations differed significantly among metabolizer statuses (mean 56.8 ± 27.1 ng/ml in normal metabolizers vs. 69.6 ± 30.1 ng/ml in intermediate metabolizers, p = 0.042), but these differences did not affect cognitive function over three years as assessed by MMSE. Additionally, there was no significant correlation between donepezil plasma concentration and adverse events. Our study is the first to elucidate the associations between CYP2D6 genotype and the concentration, clinical response or adverse events of donepezil in Korean patients with AD dementia. Larger studies are necessary to fully understand the impact of CYP2D6 genetic variants on therapeutic outcomes with donepezil.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"227-233"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632836","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}

引用次数: 0

Anti-inflammatory effects of LCB 03-0110 on human corneal epithelial and murine T helper 17 cells. LCB 03-0110 对人类角膜上皮细胞和小鼠 T 辅助细胞 17 的抗炎作用。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.166

Do Vinh Truong, Beom-Seok Yang, Chiman Song

{"title":"Anti-inflammatory effects of LCB 03-0110 on human corneal epithelial and murine T helper 17 cells.","authors":"Do Vinh Truong, Beom-Seok Yang, Chiman Song","doi":"10.4196/kjpp.24.166","DOIUrl":"10.4196/kjpp.24.166","url":null,"abstract":"Dry eye disease (DED) is a complicated disorder that impacts ocular surface and tear-film stability. Inflammation has recently been reported as the core mechanism and main therapeutic target of DED. Although anti-inflammatory drugs have been developed, they still have limited efficacy and various side effects. Recent reports have suggested that kinase inhibitors are beneficial for relieving inflammation. Therefore, this study aimed to investigate the anti-inflammatory effects of LCB 03-0110, a multi-tyrosine kinase inhibitor, on representative cell-based models (HCE- 2 and Th17 cells) of DED. While tacrolimus and tofacitinib, two different anti-inflammatory drugs that have entered clinical trials for DED treatment, did not induce any anti-inflammatory responses in HCE-2 cells, LCB 03-0110 significantly suppressed the phosphorylation of P38 and ERK and reduced the expression levels of IL-6 and IL-8 in HCE-2 cells treated with either LPS or poly(I:C). Moreover, LCB 03-0110 notably decreased the expression level of IL-17A in Th17 cells in a dose-dependent manner, whereas tofacitinib promoted IL-17A production at low concentrations but inhibited its expression at concentrations greater than 1 μM. In addition, LCB 03-0110 was found to be non-toxic to both HCE-2 and Th17 cells. In conclusion, these results suggest that LCB 03-0110 would be a promising drug candidate for the treatment of DED because of its advantages over tacrolimus and tofacitinib.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"205-214"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632815","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}

引用次数: 0

Functional interplay between non-canonical inflammasomes and autophagy in inflammatory responses and diseases. 非典型炎症小体与自噬在炎症反应和疾病中的功能相互作用

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.240

Young-Su Yi

{"title":"Functional interplay between non-canonical inflammasomes and autophagy in inflammatory responses and diseases.","authors":"Young-Su Yi","doi":"10.4196/kjpp.24.240","DOIUrl":"10.4196/kjpp.24.240","url":null,"abstract":"The inflammasome is a cytosolic multiprotein platform that plays a key role in the inflammatory response, an essential innate immune response that protects the body from pathogens and cellular danger signals. Autophagy is a fundamental cellular mechanism that maintains homeostasis through the elimination and recycling of dysfunctional molecules and subcellular elements. Many previous studies have demonstrated a functional interplay between canonical inflammasomes that were earlier discovered and autophagy in inflammatory responses and diseases. Given the increasing evidence that non-canonical inflammasomes are unique and key factors in inflammatory responses, the functional interplay between non-canonical inflammasomes and autophagy is noteworthy. Recent studies have demonstrated that non-canonical inflammasomes and autophagy are functionally correlated with inflammatory responses and diseases. This review comprehensively discusses recent studies that have investigated the functional interplay of non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4, with autophagy and autophagy-related proteins in inflammatory responses and diseases and provides insight into the development of novel anti-inflammatory therapeutics by modulating the functional interplay between non-canonical inflammasomes and autophagy.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"129-138"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632821","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}

引用次数: 0

Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway. 塔斯奎尼莫德通过下调 HDAC4/p21 通路促进卵巢癌细胞对顺铂的敏感性。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.132

Zhao Li, Ya-Hong Wu, Ye-Qing Guo, Xiao-Jia Min, Ying Lin

{"title":"Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway.","authors":"Zhao Li, Ya-Hong Wu, Ye-Qing Guo, Xiao-Jia Min, Ying Lin","doi":"10.4196/kjpp.24.132","DOIUrl":"10.4196/kjpp.24.132","url":null,"abstract":"To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms. RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"191-204"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632834","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}

引用次数: 0