Biomolecules & Therapeutics最新文献

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

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

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

Paeoniflorin Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage by Activating Nrf2-Mediated HO-1 Signaling. 芍药苷通过激活nrf2介导的HO-1信号通路保护高糖诱导的视网膜色素上皮细胞免受氧化损伤。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2025-04-17 DOI: 10.4062/biomolther.2025.025

Cheol Park, Hee-Jae Cha, Su Hyun Hong, Jeong Sook Noh, Sang Hoon Hong, Gi Young Kim, Jung-Hyun Shim, Jin Won Hyun, Yung Hyun Choi

{"title":"Paeoniflorin Protects Retinal Pigment Epithelial Cells from High Glucose-Induced Oxidative Damage by Activating Nrf2-Mediated HO-1 Signaling.","authors":"Cheol Park, Hee-Jae Cha, Su Hyun Hong, Jeong Sook Noh, Sang Hoon Hong, Gi Young Kim, Jung-Hyun Shim, Jin Won Hyun, Yung Hyun Choi","doi":"10.4062/biomolther.2025.025","DOIUrl":"https://doi.org/10.4062/biomolther.2025.025","url":null,"abstract":"Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"518-528"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966923","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

Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice. 应激通过增加Tg2576小鼠SPNS2表达加速抑郁样行为。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2025-04-08 DOI: 10.4062/biomolther.2024.200

Seung Sik Yoo, Yuri Kim, Dong Won Lee, Hyeon Joo Ham, Jung Ho Park, In Jun Yeo, Ju Young Chang, Jaesuk Yun, Dong Ju Son, Sang-Bae Han, Jin Tae Hong

{"title":"Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice.","authors":"Seung Sik Yoo, Yuri Kim, Dong Won Lee, Hyeon Joo Ham, Jung Ho Park, In Jun Yeo, Ju Young Chang, Jaesuk Yun, Dong Ju Son, Sang-Bae Han, Jin Tae Hong","doi":"10.4062/biomolther.2024.200","DOIUrl":"10.4062/biomolther.2024.200","url":null,"abstract":"To investigate the relationship between depression and AD, water avoidance stress (WAS) was induced for 10 days in both Tg2576 mice and wild-type (WT) mice. After WAS, memory function and depressive-like behavior were investigated in Tg2576 mice. Tg2576 WAS mice exhibited more depressive-like behaviors than WT WAS and Tg2576 control (CON) mice. Strikingly, Tg2576 CON mice showed more depressive-like behaviors than WT mice. Moreover, corticosterone and phospho-glucocorticoid receptor (p-GR) levels were also higher in Tg2576 WAS mice in comparison to Tg2576 CON mice. Spinster homologue 2 (SPNS2) is a member of non-ATP-dependent transporter. The role of SPNS2 was widely known as a sphingosine-1-phosphate (S1P) transporter, which export intracellular S1P from cells. Using GEO database to analyze SPNS2 gene expression changes in patients with AD and depression, we show that SPNS2 gene expression correlates with AD and depression. Interestingly, Tg2576 WAS mice displayed significantly increased levels of SPNS2 w1hen compared to Tg2576 CON counterparts. SPNS2 levels were also higher in Tg2576 CON mice in comparison with WT CON mice. Remarkably, we found a decrease in S1P brain levels and an increase in S1P serum levels of Tg2576 WAS mice in comparison with Tg2576 CON mice. Accordingly, WAS induced group further decreased S1P levels in the brains. However, the level in the serum further increased in comparison with non-induced group. Therefore, these results suggest that AD and depression could be associated, and that Tg2576 transgenic mice are more susceptible to stress-induced depression through the release of S1P by SPNS2 up-regulation.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"417-428"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802285","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

The SIRT6 Activator MDL-800 Inhibits PPARα and Fatty acid Oxidation-Related Gene Expression in Hepatocytes. SIRT6激活因子MDL-800抑制肝细胞中PPARα和脂肪酸氧化相关基因的表达

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI: 10.4062/biomolther.2024.251

Yeonsoo Kim, Hyeokjin Lim, Ye Eun Cho, Seonghwan Hwang

{"title":"The SIRT6 Activator MDL-800 Inhibits PPARα and Fatty acid Oxidation-Related Gene Expression in Hepatocytes.","authors":"Yeonsoo Kim, Hyeokjin Lim, Ye Eun Cho, Seonghwan Hwang","doi":"10.4062/biomolther.2024.251","DOIUrl":"10.4062/biomolther.2024.251","url":null,"abstract":"A histone deacetylase SIRT6 regulates the transcription of various genes involved in lipid metabolism. Fatty acid (FA) oxidation plays a pivotal role in maintaining hepatic lipid homeostasis, and its dysregulation significantly contributes to lipotoxicity and inflammation, driving the progression of steatotic liver disease. While SIRT6 is known to activate peroxisome proliferator-activated receptor-alpha (PPARα), a central regulator of FA oxidation, the development of SIRT6 activators capable of enhancing FA oxidation and mitigating steatotic liver disease has yet to be achieved. This study evaluated the effect of MDL-800, a selective SIRT6 activator, on the expression of PPARα and genes related to FA oxidation. In AML12 mouse hepatocytes, MDL-800 treatment activated SIRT6 but unexpectedly decreased the expression of PPARα and its FA oxidation-associated target genes. Furthermore, OSS128167, a selective SIRT6 inhibitor, did not reverse the suppressive effects of MDL-800 on PPARα, suggesting that MDL-800 downregulates PPARα and FA oxidation-related genes through a mechanism independent of SIRT6 activation. Mechanistic investigations revealed that MDL-800 increased the production of reactive oxygen species and activated stress kinases. The inhibition of PPARα by MDL-800 was reversed by co-treatment with the antioxidant N-acetylcysteine or the JNK inhibitor SP600125. In summary, MDL-800 suppresses PPARα and FA oxidation-related genes primarily through the induction of oxidative stress in hepatocytes, independent of its role as a SIRT6 activator.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"438-446"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810267","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

Inhibition of Sphingosine-1-Phosphate Receptor 2 (S1P₂) Attenuates Imiquimod-Induced Psoriasis-Like Skin Inflammation in BALB/c Mice. 抑制鞘氨醇-1-磷酸受体2 （S1P2）可减轻吡喹莫德诱导的BALB/c小鼠银屑病样皮肤炎症

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 Epub Date: 2025-04-23 DOI: 10.4062/biomolther.2024.197

Ju-Hyun Lee, Dong-Soon Im

{"title":"Inhibition of Sphingosine-1-Phosphate Receptor 2 (S1P2) Attenuates Imiquimod-Induced Psoriasis-Like Skin Inflammation in BALB/c Mice.","authors":"Ju-Hyun Lee, Dong-Soon Im","doi":"10.4062/biomolther.2024.197","DOIUrl":"https://doi.org/10.4062/biomolther.2024.197","url":null,"abstract":"Serum and epidermal levels of sphingosine 1-phosphate (S1P) are higher in patients with psoriasis than healthy subjects. Although roles of type 1 S1P receptor, S1P1, in the development of psoriasis has intensively been investigated, roles of S1P2 have not been elucidated. We aim to investigate whether blockage of S1P2 reduce imiquimod-induced psoriasis-like dermatitis using an S1P2 antagonist, JTE-013, in combination with S1pr2 wild-type (WT) and knock-out (KO) BALB/c mice. Imiquimod induced increase of erythematous papules and plaques with silver scaling, whereas administration of JTE-013 significantly suppressed those increases in S1pr2 WT mice. Deficiency of S1pr2 gene reduced the imiquimod-induced symptoms. Imiquimod increased mRNA expression levels of pro-inflammatory Th1/Th17 cytokines, whereas JTE-013 significantly suppressed those increases in S1pr2 WT mice. Deficiency of S1pr2 gene also suppressed the imiquimod-induced pro-inflammatory cytokine expression. Imiquimod induced enlargement of lymph nodes and spleens, whereas JTE-013 suppressed them in S1pr2 WT mice. Imiquimod induced increase of pro-inflammatory Th1/Th17 cytokine levels and Th17 cell numbers in lymph nodes and spleens, whereas JTE-013 suppressed them in S1pr2 WT mice. In summary, the present results suggest that blockage of S1P2 could suppress the characteristics of psoriasis-form dermatitis and be a therapeutic strategy.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 3","pages":"544-553"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973774","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 "Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress" [Biomol Ther 32(3), 349-360 (2024)]. “Morroniside保护C2C12成肌细胞免受ros介导的线粒体损伤和内质网应激的氧化损伤”[生物学报，32(3),349-360(2024)]。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2025-05-01 DOI: 10.4062/biomolther.2025.006

Hyun Hwangbo, Cheol Park, EunJin Bang, Hyuk Soon Kim, Sung-Jin Bae, Eunjeong Kim, Youngmi Jung, Sun-Hee Leem, Young Rok Seo, Su Hyun Hong, Gi-Young Kim, Jin Won Hyun, Yung Hyun Choi

引用次数: 0