Biomolecules & Therapeutics最新文献_第2页

OZ-001 Suppresses the Growth of Triple-Negative Breast Cancer and Pancreatic Cancer by Targeting STAT3 Phosphorylation and the Calcium Signaling Pathway. OZ-001通过STAT3磷酸化和钙信号通路抑制三阴性乳腺癌和胰腺癌的生长

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-07-01 Epub Date: 2025-06-10 DOI: 10.4062/biomolther.2025.012

Jisun Kim, Hyun-Kyoung Kim, SunHye Lee, Young-Jin Yu, Ahsan Ullah, Eui Yun Kim, Ho Yoo, Han-Jung Chae

{"title":"OZ-001 Suppresses the Growth of Triple-Negative Breast Cancer and Pancreatic Cancer by Targeting STAT3 Phosphorylation and the Calcium Signaling Pathway.","authors":"Jisun Kim, Hyun-Kyoung Kim, SunHye Lee, Young-Jin Yu, Ahsan Ullah, Eui Yun Kim, Ho Yoo, Han-Jung Chae","doi":"10.4062/biomolther.2025.012","DOIUrl":"10.4062/biomolther.2025.012","url":null,"abstract":"Triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC) are aggressive malignancies characterized by uncontrolled tumor growth, high recurrence rates, and resistance to chemotherapy. OZ-001 is a small molecule with a dual mechanism of action targeting T-type Ca2+ channels and inhibiting activation of the signal transducer and activator of transcription 3 (STAT3) protein. These properties suggest a potential use as a therapeutic agent for TNBC and PDAC, addressing the urgent need for effective treatments. This study evaluates the anticancer efficacy and underlying mechanism of action of OZ-001. The anticancer activities of OZ-001 were assessed in MDA-MB-231 cells (against TNBC) and MIA PaCa-2 cells (against PDAC) through analyses of cell viability, apoptosis, protein characterization, and cell cycles. Protein affinity and intracellular calcium measurements were conducted to investigate its effects on STAT3 and T-type calcium channels. Xenograft animal models were developed using MDA-MB-231 and MIA PaCa-2 cells to evaluate the in vivo anticancer effects of OZ-001. We found that OZ-001 induced caspase-dependent MDA-MB-231 and MIA PaCa-2 cells by modulating Bcl-2 family proteins. It suppressed STAT3 phosphorylation, reducing the expression of survivin, Bcl-2, and cyclin D1. Specifically, OZ-001 blocked T-type calcium channels, which reduced intracellular calcium levels and activated apoptotic pathways. In vivo, oral administration of OZ-001 significantly reduced tumor growth in both xenograft models, likely due to diminished STAT3 phosphorylation and associated tumorigenic processes. These findings demonstrate the potential of OZ-001 to serve as an effective therapeutic agent for treating TNBC and PDAC.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"652-669"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257306","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

Association between Prenatal Particulate Matter Exposure and Neuropsychiatric Disorders Development. 产前颗粒物暴露与神经精神疾病发展的关系

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-07-01 Epub Date: 2025-06-11 DOI: 10.4062/biomolther.2025.031

Ho Jung Bae, Tamanna Jahan Mony, Se Jin Park

{"title":"Association between Prenatal Particulate Matter Exposure and Neuropsychiatric Disorders Development.","authors":"Ho Jung Bae, Tamanna Jahan Mony, Se Jin Park","doi":"10.4062/biomolther.2025.031","DOIUrl":"10.4062/biomolther.2025.031","url":null,"abstract":"This comprehensive review explores the relationship between prenatal exposure to particulate matter (PM) air pollution and the development of various neuropsychiatric disorders in offspring. Air pollution, specifically by PM, is a global health concern, with PM2.5 and PM10 being the most detrimental to health. This review delves into the impact of prenatal PM exposure on neurodevelopment and the onset of disorders such as cognitive impairment, Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), anxiety, depression, and schizophrenia. Utilizing data from international databases and focusing on full-text research papers from 2013 to 2023, we identified 18 relevant studies that explore the association between prenatal PM exposure and subsequent neuropsychiatric outcomes. The review discusses the potential mechanisms underlying these associations, including systemic inflammation, oxidative stress, and disruptions in the gut-brain axis. Key findings include the detrimental effects of PM exposure on fetal brain development, leading to cognitive deficits, heightened risk of ASD, ADHD, and altered mental health outcomes. Moreover, the review highlights the need for further research to unravel the complex interplay of genetic, environmental, and individual factors in the development of these disorders. The implications of these findings underscore the importance of reducing air pollution exposure, particularly during pregnancy, to safeguard fetal brain development and prevent neuropsychiatric disorders in offspring.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"557-571"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265199","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

Amelioration of Carrageenan/Kaolin-Induced Arthritis by Benzylideneacetophenone Derivatives in Rats. 苯并苯乙酮衍生物对卡拉胶/高岭土诱导大鼠关节炎的改善作用。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-07-01 Epub Date: 2025-06-13 DOI: 10.4062/biomolther.2024.242

Seungmin Kang, Mijin Kim, Hyun-Su Lee, Seikwan Oh

{"title":"Amelioration of Carrageenan/Kaolin-Induced Arthritis by Benzylideneacetophenone Derivatives in Rats.","authors":"Seungmin Kang, Mijin Kim, Hyun-Su Lee, Seikwan Oh","doi":"10.4062/biomolther.2024.242","DOIUrl":"10.4062/biomolther.2024.242","url":null,"abstract":"This study was done to evaluate the inhibitory effects of benzylideneacetophenone derivatives (JCII) on rheumatoid arthritis (RA). This was done by using carrageenan/kaolin-induced arthritis in rats and human RA fibroblast-like synoviocytes (FLS). In FLS cells and Jurkat T cells, JCII compounds at 5, 10, and 20 μM were used to treat the cells followed by stimulation with IL-1β (10 ng/mL) for FLS cells and PMA/A23187 for Jurkat T cells. Inflammatory mediators and cytokines related to activated T cell functions were then analyzed using RT-PCR and ELISA. In rats, JCII compounds at 1, 5, and 10 mg/kg were given intraperitoneally daily for 6 days. Thereafter, arthritis evaluation was conducted by measuring squeaking scores, knee thickness, and WDR as well as histological assessments of the knee joints. Inflammatory mediators were also measured in the serum of the rats. JCII compounds given at 10 mg/kg significantly alleviated arthritis symptoms especially on day 5 or day 6 following arthritis in rats. The histological results were found to be consistent with the behavioral evaluation that were measured. In stimulated FLS cells, the same pattern was seen wherein JCII compounds also decreased the levels of different inflammatory mediators and MMPs. Also, the phosphorylation of JNK and p38 MAPK pathways were inhibited by JCII compounds. In addition, the level of TNF-α from activated T cells were downregulated by JCII treatment. These show that JCII compounds show a potential anti-arthritic effect at least via anti-inflammation and can be used potentially for the treatment in arthritis and the accompanying inflammatory disease.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"680-691"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282251","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

Identification of Autophagy-Related Prognostic Signature for Glioblastoma Standard Therapy. 胶质母细胞瘤标准治疗中自噬相关预后特征的鉴定。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-07-01 Epub Date: 2025-06-30 DOI: 10.4062/biomolther.2025.010

Min Ju Lee, Hong Seok Choi, Eun Jeong Min, Seong Bin Jo, Jae-Sung Park, Young Ae Joe

{"title":"Identification of Autophagy-Related Prognostic Signature for Glioblastoma Standard Therapy.","authors":"Min Ju Lee, Hong Seok Choi, Eun Jeong Min, Seong Bin Jo, Jae-Sung Park, Young Ae Joe","doi":"10.4062/biomolther.2025.010","DOIUrl":"10.4062/biomolther.2025.010","url":null,"abstract":"Glioblastoma is an aggressive brain tumor with poor prognosis and survival. Autophagy is induced in tumor cells under stress conditions such as treatment with chemotherapeutic agents and radiotherapy (RT), causing resistance to therapy. Thus, we analyzed autophagy-related genes using public databases to investigate a novel prognostic autophagy signature for glioblastoma patients who received temozolomide (TMZ) and RT. The TCGA and CGGA RNA sequencing datasets were classified for TMZ/RT-treated patient groups, and autophagy-related genes were obtained from Human Autophagy Database (HADb). Through sequential analyses of the datasets using univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and log-rank test, four genes (ATG9B, HSPA5, ITGA3, and RAC1) were selected to construct a prognostic risk score model. Multivariate Cox regression analysis of the risk score of these genes in the TCGA dataset demonstrated that TMZ/RT-treated patients with high-risk scores had significantly poorer overall survival and progression-free survival. Most patients designated as a high-risk group were also identified as IDH wild-type and mesenchymal subtypes. The autophagy signature was also validated in the CGGA RNA sequencing dataset and TCGA microarray dataset. Functional analysis of the autophagy signature through gene set enrichment and gene ontology analyses revealed enrichment of cellular responses to stress and the unfolded protein response. We also validated the higher expression of these genes and autophagy flux in TMZ-resistant glioblastoma cells than in TMZ-sensitive cells. Therefore, the autophagy-related gene set could serve as an independent prognostic biomarker for predicting the response to standard therapy in glioblastoma patients.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 4","pages":"606-620"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538034","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

Toxoplasma gondii GRA16 Suppresses Aerobic Glycolysis by Downregulating c-Myc and TERT Expressions in Colorectal Cancer Cells. 刚地弓形虫GRA16通过下调结直肠癌细胞c-Myc和TERT表达抑制需氧糖酵解

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-07-01 Epub Date: 2025-06-25 DOI: 10.4062/biomolther.2025.040

Ji-Eun Lee, Seung-Hwan Seo, Do-Won Ham, Eun-Hee Shin

{"title":"Toxoplasma gondii GRA16 Suppresses Aerobic Glycolysis by Downregulating c-Myc and TERT Expressions in Colorectal Cancer Cells.","authors":"Ji-Eun Lee, Seung-Hwan Seo, Do-Won Ham, Eun-Hee Shin","doi":"10.4062/biomolther.2025.040","DOIUrl":"10.4062/biomolther.2025.040","url":null,"abstract":"Despite its relatively low adenosine triphosphate (ATP) production efficiency, cancer cells reprogram their metabolism to utilize aerobic glycolysis for rapid proliferation. This \"Warburg effect\" not only provides biosynthetic precursors but also creates a tumor-favorable microenvironment. Key oncogenic regulators such as protein kinase B (AKT), nuclear factor kappa B (NF-κB), and cellular myelocytomatosis oncogene (c-Myc) enhance glycolytic activity by inducing the expression of enzymes including glucose transporters (GLUTs), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and monocarboxylate transporters (MCTs). Moreover, telomerase reverse transcriptase (TERT), beyond its canonical role in telomere maintenance, also promotes glycolysis via the NF-κB and c-Myc pathways. From a therapeutic perspective, aerobic glycolysis contributes to glucose-mediated chemoresistance, limiting the efficacy of irinotecan in colorectal cancer (CRC). In this study, we investigated the role of Toxoplasma gondii-derived dense granule protein 16 (GRA16) in modulating glycolysis and irinotecan sensitivity. In HCT116 CRC cells stably expressing GRA16, AKT and NF-κB signaling were suppressed, leading to the downregulation of c-Myc and TERT. This resulted in decreased expression of GLUTs, HK2, LDHA, and MCTs, ultimately reducing glucose uptake and lactate production. Functional assays revealed that GRA16 induced G2/M cell cycle arrest, increased apoptosis, and suppressed proliferation. Notably, GRA16-expressing cells treated with irinotecan exhibited increased Sub-G1 accumulation and late-apoptotic and necrotic populations. Furthermore, siRNA-mediated silencing of c-Myc confirmed its key role in regulating TERT and glycolytic enzymes. These findings indicate that GRA16 suppresses aerobic glycolysis via the c-Myc/TERT axis and enhances irinotecan sensitivity, offering a promising strategy to overcome chemoresistance in CRC.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"621-635"},"PeriodicalIF":3.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12215043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483097","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

Andrographolide as a Multi-Target Therapeutic Agent in Diabetic Nephropathy: Insights into STAT3/PI3K/Akt Pathway Modulation. 穿心莲内酯作为糖尿病肾病的多靶点治疗剂：STAT3/PI3K/Akt通路调节的见解

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI: 10.4062/biomolther.2024.209

Yuan Yin, Jing He, Yu Fang, Min Wei, Wang Zhang

{"title":"Andrographolide as a Multi-Target Therapeutic Agent in Diabetic Nephropathy: Insights into STAT3/PI3K/Akt Pathway Modulation.","authors":"Yuan Yin, Jing He, Yu Fang, Min Wei, Wang Zhang","doi":"10.4062/biomolther.2024.209","DOIUrl":"10.4062/biomolther.2024.209","url":null,"abstract":"Diabetic nephropathy (DN) remains a leading cause of end-stage renal disease (ESRD), driven by chronic inflammation, oxidative stress, and apoptosis. Current therapies targeting glycemic and blood pressure control fail to address the underlying molecular mechanisms of DN. This study investigates the therapeutic potential of andrographolide (AD), a diterpenoid lactone from Andrographis paniculata, in mitigating DN by modulating key molecular pathways. Through integrative network pharmacology, molecular docking, and in vivo/in vitro experiments, 107 overlapping DN-related targets were identified, with STAT3, PI3K, and AKT1 emerging as core nodes. Molecular docking revealed high binding affinities between AD and these targets, supporting its modulatory potential. In vivo, AD significantly improved renal function in streptozotocin-induced DN rats, reducing proteinuria, glomerular hypertrophy, and renal fibrosis. AD also attenuated oxidative stress, decreased pro-inflammatory cytokine levels, and enhanced antioxidant enzyme activities, demonstrating systemic anti-inflammatory and antioxidative effects. In vitro studies further confirmed that AD alleviates podocyte oxidative stress and apoptosis under high glucose conditions by suppressing the RAGE-NF-κB and STAT3/PI3K/Akt pathways. Histological analyses revealed substantial improvements in renal architecture, including reductions in fibrosis and mesangial expansion. These results underscore AD's multi-target mechanism, directly addressing DN's core pathological drivers, including inflammation, oxidative stress, and apoptosis. As a natural compound with notable safety and efficacy, AD holds promise as an adjunct or standalone therapeutic agent for DN. This study establishes a robust preclinical foundation for AD, warranting further exploration in clinical trials and its potential application in other diabetic complications.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"529-543"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778892","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

Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats. 白藜芦醇对对乙酰氨基酚急性肝损伤的保护作用及其对托法替尼处置的影响。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2024-12-13 DOI: 10.4062/biomolther.2024.184

Hyeon Gyeom Choi, So Yeon Park, Sung Hun Bae, Sun-Young Chang, So Hee Kim

{"title":"Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats.","authors":"Hyeon Gyeom Choi, So Yeon Park, Sung Hun Bae, Sun-Young Chang, So Hee Kim","doi":"10.4062/biomolther.2024.184","DOIUrl":"10.4062/biomolther.2024.184","url":null,"abstract":"Tofacitinib, which is used to treat rheumatoid arthritis (RA), is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, CYP3A1/2 and CYP2C11. Acetaminophen (APAP), which is frequently used for pain relief in patients with RA, can induce acute liver injury (ALI) when taken in excess, profoundly affecting drug metabolism. Resveratrol (RVT) is a polyphenolic compound with hepatoprotective properties. This study investigated the protective effects of RVT against APAP-induced ALI in rats, and explored its influence on the pharmacokinetics of tofacitinib. In ALI rats, both intravenous and oral administration of tofacitinib resulted in a significant (207% and 181%) increase in the area under the plasma concentration-time curve (AUC), primarily driven by a substantial reduction (66.1%) in non-renal clearance (CLNR) compared to that in control (CON) rats. Notably, RVT administration in ALI rats provided effective liver protection, partially restoring liver function, as evidenced by normalized glutamate oxaloacetate transaminase levels and the pharmacokinetic parameters, AUC and CLNR, closer to those observed in untreated CON rats (117% and 81.9%, respectively). These findings highlight the importance of considering the potential interactions between RVT or polyphenol-rich natural products and medications in patients with ALI in clinical practice.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"501-509"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817057","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

Hederacoside C Modulates EGF-Induced MUC5AC Mucin Gene Expression by Regulating the MAPK Signaling Pathway in Human Airway Epithelial Cells. Hederacoside C通过调控MAPK信号通路调节egf诱导的人气道上皮细胞MUC5AC粘蛋白基因表达

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2025-04-30 DOI: 10.4062/biomolther.2025.054

Rajib Hossain, Md Solayman Hossain, Hyun Jae Lee, Choong Jae Lee

{"title":"Hederacoside C Modulates EGF-Induced MUC5AC Mucin Gene Expression by Regulating the MAPK Signaling Pathway in Human Airway Epithelial Cells.","authors":"Rajib Hossain, Md Solayman Hossain, Hyun Jae Lee, Choong Jae Lee","doi":"10.4062/biomolther.2025.054","DOIUrl":"https://doi.org/10.4062/biomolther.2025.054","url":null,"abstract":"This study aimed to evaluate the potential of hederacoside C, an active compound isolated from Hedera helix, which has been used for managing inflammatory respiratory diseases, in attenuating epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with hederacoside C for 30 min and subsequently stimulated with EGF for 24 h. The study also examined the effect of hederacoside C on the EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway. The results showed that hederacoside C inhibited MUC5AC mucin mRNA expression and the production of mucous glycoproteins by suppressing the phosphorylation of the EGF receptor (EGFR), as well as the phosphorylation of MAPK/extracellular signal-regulated kinase (ERK) 1/2 (MEK1/2), p38 MAPK, ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings suggest that hederacoside C has the potential to reduce EGF-induced mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway in NCI-H292 cells.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"510-517"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961737","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

Microplastics Accumulation Induces Kynurenine-Derived Neurotoxicity in Cerebral Organoids and Mouse Brain. 微塑料积累诱导犬尿氨酸来源的脑类器官和小鼠脑神经毒性。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI: 10.4062/biomolther.2024.185

Sung Bum Park, Jeong Hyeon Jo, Seong Soon Kim, Won Hoon Jung, Myung Ae Bae, Byumseok Koh, Ki Young Kim

{"title":"Microplastics Accumulation Induces Kynurenine-Derived Neurotoxicity in Cerebral Organoids and Mouse Brain.","authors":"Sung Bum Park, Jeong Hyeon Jo, Seong Soon Kim, Won Hoon Jung, Myung Ae Bae, Byumseok Koh, Ki Young Kim","doi":"10.4062/biomolther.2024.185","DOIUrl":"10.4062/biomolther.2024.185","url":null,"abstract":"Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression. In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"447-457"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778896","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

MLKL Inhibitor Reduces Oxidative Stress, Inflammation, and Dopaminergic Neuronal Cell Death in MPTP-Induced Parkinson's Disease Mouse Model. MLKL抑制剂在mptp诱导的帕金森病小鼠模型中减少氧化应激、炎症和多巴胺能神经元细胞死亡

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2025-04-15 DOI: 10.4062/biomolther.2025.049

Do-Yeon Kim, Yea-Hyun Leem, Hee-Sun Kim

{"title":"MLKL Inhibitor Reduces Oxidative Stress, Inflammation, and Dopaminergic Neuronal Cell Death in MPTP-Induced Parkinson's Disease Mouse Model.","authors":"Do-Yeon Kim, Yea-Hyun Leem, Hee-Sun Kim","doi":"10.4062/biomolther.2025.049","DOIUrl":"https://doi.org/10.4062/biomolther.2025.049","url":null,"abstract":"Parkinson's disease (PD) is a movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). Recent studies have shown that necroptosis is involved in the development of inflammatory and neurodegenerative diseases. Receptor-interacting protein kinase (RIPK)1, RIPK3, and mixed lineage kinase domain-like protein (MLKL) play key roles in necroptosis, with MLKL being the final executor of necroptosis. Necrosulfonamide (NSA) is a specific inhibitor of MLKL, and its therapeutic effects in various inflammatory and neurological disorders have been previously reported. However, its role in PD has not yet been clearly demonstrated. In this study, we examined the effects of NSA in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. NSA reduced dopaminergic cell death and restored the expression of neurotrophic factors, such as BDNF, GDNF, and PGC-1α, in the SN region of MPTP mice. In addition, NSA inhibited microglial/astrocyte activation and the expression of proinflammatory markers, such as iNOS, TNF-α, IL-1β, and IL-6. NSA also reduced oxidative stress markers, such as 8-OHdG and 4-HNE, while enhancing Nrf2-driven antioxidant enzymes, including HO-1, catalase, MnSOD, GCLC, and GCLM. We found that NSA inhibited MLKL phosphorylation in dopaminergic neurons and microglia, which may have reduced neuronal cell death and inflammation. Therefore, NSA-mediated suppression of dopaminergic neuronal cell death, inflammation, and oxidative stress may have therapeutic potential in PD.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"429-437"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962549","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