Biomolecules & Therapeutics最新文献_第7页

β-Lapachone Exerts Hypnotic Effects via Adenosine A₁ Receptor in Mice. β-拉帕醌通过腺苷 A1 受体对小鼠产生催眠作用

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-21 DOI: 10.4062/biomolther.2024.106

Do Hyun Lee, Hye Jin Jee, Yi-Sook Jung

{"title":"β-Lapachone Exerts Hypnotic Effects via Adenosine A1 Receptor in Mice.","authors":"Do Hyun Lee, Hye Jin Jee, Yi-Sook Jung","doi":"10.4062/biomolther.2024.106","DOIUrl":"10.4062/biomolther.2024.106","url":null,"abstract":"Sleep is one of the most essential physiological phenomena for maintaining health. Sleep disturbances, such as insomnia, are often accompanied by psychiatric or physical conditions such as impaired attention, anxiety, and stress. Medication used to treat insomnia have concerns about potential side effects with long-term use, so interest in the use of alternative medicine is increasing. In this study, we investigated the hypnotic effects of β-lapachone (β-Lap), a natural naphthoquinone compound, using pentobarbital-induced sleep test, immunohistochemistry, real-time PCR, and western blot in mice. Our results indicated that β-Lap exerts a significant hypnotic effect by showing a decrease in sleep onset latency and an increase in total sleep time in pentobarbital-induced sleep model. The results of c-Fos immunostaining showed that β-Lap decreased neuronal activity in the basal forebrain and lateral hypothalamus, which are wakefulness-promoting brain regions, while increasing in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly abolished by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1 receptor (A1R) antagonist. Western blot analysis showed that β-Lap increased extracellular signalregulated kinase phosphorylation and nuclear factor-kappa B translocation from the cytoplasm to the nucleus; these effects were inhibited by DPCPX. Additionally, β-Lap increased the mRNA levels of A1R. Taken together, these results suggest that β-Lap exerts hypnotic effects, potentially through A1R.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"531-539"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008227","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

Glycogen Phosphorylase Inhibitor Promotes Hair Growth via Protecting from Oxidative-Stress and Regulating Glycogen Breakdown in Human Hair follicles. 糖原磷酸化酶抑制剂通过保护人体毛囊免受氧化应激和调节糖原分解促进毛发生长

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-06 DOI: 10.4062/biomolther.2024.098

Bomi Park, Daeun Kim, Hairu Zhao, SoonRe Kim, Byung Cheol Park, Sanghwa Lee, Yurim Lee, Hee Dong Park, Dongchul Lim, Sunyoung Ryu, Jae Sung Hwang

{"title":"Glycogen Phosphorylase Inhibitor Promotes Hair Growth via Protecting from Oxidative-Stress and Regulating Glycogen Breakdown in Human Hair follicles.","authors":"Bomi Park, Daeun Kim, Hairu Zhao, SoonRe Kim, Byung Cheol Park, Sanghwa Lee, Yurim Lee, Hee Dong Park, Dongchul Lim, Sunyoung Ryu, Jae Sung Hwang","doi":"10.4062/biomolther.2024.098","DOIUrl":"10.4062/biomolther.2024.098","url":null,"abstract":"Hair growth cycles are mainly regulated by human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). Protecting hDPCs from excessive oxidative stress and hORSCs from glycogen phosphorylase (PYGL) is crucial to maintaining the hair growth phase, anagen. In this study, we developed a new PYGL inhibitor, Hydroxytrimethylpyridinyl Methylindolecarboxamide (HTPI) and assessed its potential to prevent hair loss. HTPI reduced oxidative damage, preventing cell death and restored decreased level of anagen marker ALP and its related genes induced by hydrogen peroxide in hDPCs. Moreover, HTPI inhibited glycogen degradation and induced cell survival under glucose starvation in hORSCs. In ex-vivo culture, HTPI significantly enhanced hair growth compared to the control with minoxidil showing comparable results. Overall, these findings suggest that HTPI has significant potential as a therapeutic agent for the prevention and treatment of hair loss.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"640-646"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892804","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

Gilteritinib Reduces FLT3 Expression in Acute Myeloid Leukemia Cells. 吉利替尼能减少急性髓性白血病细胞中的 FLT3 表达

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2023.215

Thị Lam Thái, Sun-Young Han

{"title":"Gilteritinib Reduces FLT3 Expression in Acute Myeloid Leukemia Cells.","authors":"Thị Lam Thái, Sun-Young Han","doi":"10.4062/biomolther.2023.215","DOIUrl":"10.4062/biomolther.2023.215","url":null,"abstract":"Acute myeloid leukemia (AML) is a genetically diverse and challenging malignancy, with mutations in the FLT3 gene being particularly common and deleterious. Gilteritinib, a potent FLT3 inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory AML with FLT3 mutations. Although gilteritinib was developed based on its inhibitory activity against FLT3 kinase, it is important to understand the precise mechanisms of its antileukemic activity in managing drug resistance and discovering biomarkers. This study was designed to elucidate the effect of gilteritinib on the FLT3 expression level. The results showed that gilteritinib induced a dose-dependent decrease in both FLT3 phosphorylation and expression. This reduction was particularly pronounced after 48 h of treatment. The decrease in FLT3 expression was found to be independent of changes in FLT3 mRNA transcription, suggesting post-transcriptional regulatory mechanisms. Further studies were performed in various AML cell lines and cells with both FLT3 wild-type and FLT3 mutant exhibited FLT3 reduction by gilteritinib treatment. In addition, other FLT3 inhibitors were evaluated for their ability to reduce FLT3 expression. Other FLT3 inhibitors, midostaurin, crenolanib, and quizartinib, also reduced FLT3 expression, consistent with the effect of gilteritinib. These findings hold great promise for optimizing gilteritinib treatment in AML patients. However, it is important to recognize that further research is warranted to gain a full understanding of these mechanisms and their clinical implications in the context of FLT3 reduction.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"577-581"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874070","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

Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells. 多巴胺受体 D2 拮抗剂多潘立酮通过抑制 ERK/STAT3 介导的途径诱导人结肠癌 HCT116 细胞凋亡

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-06-25 DOI: 10.4062/biomolther.2024.048

So Jin Sim, Jeong-Hoon Jang, Joon-Seok Choi, Kyung-Soo Chun

{"title":"Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells.","authors":"So Jin Sim, Jeong-Hoon Jang, Joon-Seok Choi, Kyung-Soo Chun","doi":"10.4062/biomolther.2024.048","DOIUrl":"10.4062/biomolther.2024.048","url":null,"abstract":"Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase- 3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways, respectively. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"568-576"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445357","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

Decellularized Matrices for the Treatment of Tissue Defects: from Matrix Origin to Immunological Mechanisms. 用于治疗组织缺损的脱细胞基质：从基质起源到免疫机制。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2024.050

Xinyue Wang, Jiqiang Guo, Qing Yu, Luyao Zhao, Xiang Gao, Li Wang, Meiling Wen, Junrong Yan, Meiwen An, Yang Liu

{"title":"Decellularized Matrices for the Treatment of Tissue Defects: from Matrix Origin to Immunological Mechanisms.","authors":"Xinyue Wang, Jiqiang Guo, Qing Yu, Luyao Zhao, Xiang Gao, Li Wang, Meiling Wen, Junrong Yan, Meiwen An, Yang Liu","doi":"10.4062/biomolther.2024.050","DOIUrl":"10.4062/biomolther.2024.050","url":null,"abstract":"Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-β/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"509-522"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874111","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

Interleukin-1β Signaling Contributes to Cell Cycle Arrest and Apoptotic Cell Death by Leptin via Modulation of AKT and p38MAPK in Hepatocytes. 白细胞介素-1β信号通过调节肝细胞中的 AKT 和 p38MAPK 促使细胞周期停滞和瘦素导致细胞凋亡

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2023.232

Ananda Baral, Pil-Hoon Park

{"title":"Interleukin-1β Signaling Contributes to Cell Cycle Arrest and Apoptotic Cell Death by Leptin via Modulation of AKT and p38MAPK in Hepatocytes.","authors":"Ananda Baral, Pil-Hoon Park","doi":"10.4062/biomolther.2023.232","DOIUrl":"10.4062/biomolther.2023.232","url":null,"abstract":"Leptin, an adipose tissue-derived hormone, has exhibited the potent hepatotoxic effects. However, the underlying molecular mechanisms are not fully understood. In this study, we have elucidated the mechanisms by which leptin exerts cytotoxic effects in hepatocytes, particularly focusing on the role of interleukin-1β (IL-1β) signaling. Leptin significantly induced maturation and secretion of IL-1β in cultured rat hepatocytes. Interestingly, inhibition of IL-1β signaling by pretreatment with an IL-1 receptor antagonist (IL-1Ra) or gene silencing of type I IL-1 receptor (IL-1R1) markedly abrogated leptin-induced cell cycle arrest. The critical role of IL-1β signaling in leptin-induced cell cycle arrest is mediated via upregulation of p16, which acts as an inhibitor of cyclin-dependent kinase. In addition, leptin-induced apoptotic cell death was relieved by inhibition of IL-1β signaling, as determined by annexin V/7-AAD binding assay. Mechanistically, IL-1β signaling contributes to apoptotic cell death and cell cycle arrest by suppressing AKT and activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Involvement of IL-1β signaling in cytotoxic effect of leptin was further confirmed in vivo using hepatocyte specific IL-1R1 knock out (IL-1R1 KO) mice. Essentially similar results were obtained in vivo, where leptin administration caused the upregulation of apoptotic markers, dephosphorylation of AKT, and p38MAPK activation were observed in wild type mice liver without significant effects in the livers of IL-1R1 KO mice. Taken together, these results demonstrate that IL-1β signaling critically contributes to leptin-induced cell cycle arrest and apoptosis, at least in part, by modulating p38MAPK and AKT signaling pathways.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"611-626"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874071","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

Investigating the Immune-Stimulating Potential of β-Glucan from Aureobasidium pullulans in Cancer Immunotherapy. 研究 Aureobasidium pullulans β-葡聚糖在癌症免疫疗法中的免疫刺激潜力

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2024.047

Jae-Hyeon Jeong, Dae-Joon Kim, Seong-Jin Hong, Jae-Hee Ahn, Dong-Ju Lee, Ah-Ra Jang, Sungyun Kim, Hyun-Jong Cho, Jae-Young Lee, Jong-Hwan Park, Young-Min Kim, Hyun-Jeong Ko

{"title":"Investigating the Immune-Stimulating Potential of β-Glucan from Aureobasidium pullulans in Cancer Immunotherapy.","authors":"Jae-Hyeon Jeong, Dae-Joon Kim, Seong-Jin Hong, Jae-Hee Ahn, Dong-Ju Lee, Ah-Ra Jang, Sungyun Kim, Hyun-Jong Cho, Jae-Young Lee, Jong-Hwan Park, Young-Min Kim, Hyun-Jeong Ko","doi":"10.4062/biomolther.2024.047","DOIUrl":"10.4062/biomolther.2024.047","url":null,"abstract":"β-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble β-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived β-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"556-567"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874072","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

Coadministration of 6-Shogaol and Levodopa Alleviates Parkinson's Disease-Related Pathology in Mice. 6-Shogaol 和左旋多巴联合用药可缓解小鼠帕金森病相关病理变化

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2024.075

Jin Hee Kim, Jin Se Kim, In Gyoung Ju, Eugene Huh, Yujin Choi, Seungmin Lee, Jun-Young Cho, Boyoung Y Park, Myung Sook Oh

{"title":"Coadministration of 6-Shogaol and Levodopa Alleviates Parkinson's Disease-Related Pathology in Mice.","authors":"Jin Hee Kim, Jin Se Kim, In Gyoung Ju, Eugene Huh, Yujin Choi, Seungmin Lee, Jun-Young Cho, Boyoung Y Park, Myung Sook Oh","doi":"10.4062/biomolther.2024.075","DOIUrl":"10.4062/biomolther.2024.075","url":null,"abstract":"Parkinson's disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the nigrostriatal pathway, leading to motor and non-motor dysfunctions, such as depression, olfactory dysfunction, and memory impairment. Although levodopa (L-dopa) has been the gold standard PD treatment for decades, it only relieves motor symptoms and has no effect on non-motor symptoms or disease progression. Prior studies have reported that 6-shogaol, the active ingredient in ginger, exerts a protective effect on dopaminergic neurons by suppressing neuroinflammation in PD mice. This study investigated whether cotreatment with 6-shogaol and L-dopa could attenuate both motor and non-motor symptoms and dopaminergic neuronal damage. Both 6-shogaol (20 mg/kg) and L-dopa (80 mg/kg) were orally administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid- induced PD model mice for 26 days. The experimental results showed that L-dopa alleviated motor symptoms, but had no significant effect on non-motor symptoms, loss of dopaminergic neuron, or neuroinflammation. However, when mice were treated with 6-shogaol alone or in combination L-dopa, an amelioration in both motor and non-motor symptoms such as depression-like behavior, olfactory dysfunction and memory impairment was observed. Moreover, 6-shogaol-only or co-treatment with 6-shogaol and L-dopa protected dopaminergic neurons in the striatum and reduced neuroinflammation in the striatum and substantia nigra. Overall, these results suggest that 6-shogaol can effectively complement L-dopa by improving non-motor dysfunction and restoring dopaminergic neurons via suppressing neuroinflammation.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"523-530"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874110","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

Aromadendrin Inhibits Lipopolysaccharide-Induced Inflammation in BEAS-2B Cells and Lungs of Mice. 芳香树突素抑制脂多糖诱导的 BEAS-2B 细胞和小鼠肺部炎症

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-02 DOI: 10.4062/biomolther.2024.022

Juhyun Lee, Ji-Won Park, Jinseon Choi, Seok Han Yun, Bong Hyo Rhee, Hyeon Jeong Jeong, Hyueyun Kim, Kihoon Lee, Kyung-Seop Ahn, Hye-Gwang Jeong, Jae-Won Lee

{"title":"Aromadendrin Inhibits Lipopolysaccharide-Induced Inflammation in BEAS-2B Cells and Lungs of Mice.","authors":"Juhyun Lee, Ji-Won Park, Jinseon Choi, Seok Han Yun, Bong Hyo Rhee, Hyeon Jeong Jeong, Hyueyun Kim, Kihoon Lee, Kyung-Seop Ahn, Hye-Gwang Jeong, Jae-Won Lee","doi":"10.4062/biomolther.2024.022","DOIUrl":"10.4062/biomolther.2024.022","url":null,"abstract":"Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells (ICs) and IL-1β/IL-6/TNF-α levels in the bronchoalveolar lavage fluid (BALF) and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 (COX-2)/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of acute lung injury (ALI) mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 (STAT3) activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1 (HO-1)/ NAD(P)H quinone dehydrogenase 1 (NQO1) in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"546-555"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874108","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 Tumoral VISTA to Overcome TKI Resistance via Downregulation of the AKT/mTOR and JAK2/STAT5 Pathways in Chronic Myeloid Leukemia. 通过抑制 CML 中的 AKT/mTOR 和 JAK2/STAT5 通路抑制肿瘤 VISTA 以克服 TKI 抗性

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-08-06 DOI: 10.4062/biomolther.2024.017

Kexin Ai, Mu Chen, Zhao Liang, Xiangyang Ding, Yang Gao, Honghao Zhang, Suwan Wu, Yanjie He, Yuhua Li

{"title":"Inhibition of Tumoral VISTA to Overcome TKI Resistance via Downregulation of the AKT/mTOR and JAK2/STAT5 Pathways in Chronic Myeloid Leukemia.","authors":"Kexin Ai, Mu Chen, Zhao Liang, Xiangyang Ding, Yang Gao, Honghao Zhang, Suwan Wu, Yanjie He, Yuhua Li","doi":"10.4062/biomolther.2024.017","DOIUrl":"10.4062/biomolther.2024.017","url":null,"abstract":"Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"582-600"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11392669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892805","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}

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