Cell Biochemistry and Biophysics最新文献_第7页

ABT263 Ameliorates Cellular Senescence, Aβ-Dependent Pathology and Cognitive Decline in Aged APP/PS1 Mice via Regulating PI3K/AKT/GSK-3β Pathways. ABT263通过调节PI3K/AKT/GSK-3β通路改善衰老APP/PS1小鼠细胞衰老、a β依赖性病理和认知能力下降。

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-04-28 DOI: 10.1007/s12013-025-01745-y

Zhi Tang, Xiao-Ling Wang, Yu-Xin Deng, Yan Xiao, Jian-Wei Xu, Li Wang, Xiao-Lan Qi

{"title":"ABT263 Ameliorates Cellular Senescence, Aβ-Dependent Pathology and Cognitive Decline in Aged APP/PS1 Mice via Regulating PI3K/AKT/GSK-3β Pathways.","authors":"Zhi Tang, Xiao-Ling Wang, Yu-Xin Deng, Yan Xiao, Jian-Wei Xu, Li Wang, Xiao-Lan Qi","doi":"10.1007/s12013-025-01745-y","DOIUrl":"10.1007/s12013-025-01745-y","url":null,"abstract":"Alzheimer's disease is defined pathologically by the irregular buildup of senile plaques, neurofibrillary tangles, and associated neuroinflammation. As aging progresses, senescent cells gradually accumulate and significantly contribute to brain dysfunction; however, the precise mechanisms driving aging remain unclear. In the current study, ABT263, a potent senolytic drug, was administered orally to APP/PS1 mice (n = 16) for five days per cycle throughout the course of two cycles, and their behavioral tests in the Morris water maze were evaluated. Using mouse hippocampal tissue, senescence-related gene expression and SASP-associated protein expression were assessed using biochemical tests and immunohistochemical labeling. The Morris water maze test results indicated that ABT263 alleviated spatial memory impairment and reduced amyloid-β (Aβ) accumulation in APP/PS1 mice. Additionally, ABT263 treatment led to a decline in senescence-associated β-galactosidase activity, p16 senescence-related gene expression, and the expression of SASP-associated proteins, including IL-6, IL-8, and MMP-1. Further investigation revealed that ABT263 enhanced the phosphorylation levels of phosphatidylinositol-3 kinase (PI3K) (Tyr458), serine/threonine kinase AKT (S473), and glycogen synthase kinase-3β (GSK-3β) (Ser9) in APP/PS1 mice. Our results showed that ABT263 protected neurons against Aβ pathology, reduced the accumulation of senescent cells, and improved cognitive decline by enhancing PI3K/AKT/GSK-3 activity.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3665-3676"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Theranostic Potential of Copper-64 ATSM Targeting MTHFD2: An In Silico Perspective on Hypoxia-Selective Imaging and Therapy. 铜-64 ATSM靶向MTHFD2的治疗潜力：低氧选择性成像和治疗的计算机视角。

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-03-24 DOI: 10.1007/s12013-025-01732-3

Abdulsalam Abuelsamen, Maram B Alhawarri, Mohammad G Al-Thiabat, Ghaseb N Makhadmeh, Tariq AlZoubi, Bilal Harieth Alrimawi, Mohammad A Khaleel

{"title":"Theranostic Potential of Copper-64 ATSM Targeting MTHFD2: An In Silico Perspective on Hypoxia-Selective Imaging and Therapy.","authors":"Abdulsalam Abuelsamen, Maram B Alhawarri, Mohammad G Al-Thiabat, Ghaseb N Makhadmeh, Tariq AlZoubi, Bilal Harieth Alrimawi, Mohammad A Khaleel","doi":"10.1007/s12013-025-01732-3","DOIUrl":"10.1007/s12013-025-01732-3","url":null,"abstract":"Hypoxia is a hallmark of the tumor microenvironment, leading to metabolic reprogramming and therapeutic resistance. The enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) supports hypoxia adaptation, making it an attractive target for cancer treatment. Copper-64 diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) exhibits selective hypoxia uptake, positioning it as a promising theranostic agent for imaging and treating hypoxic tumors. In this study, we employed molecular docking and molecular dynamics (MD) simulations to evaluate the binding, stability, and dynamic behavior of 64Cu-ATSM within the MTHFD2 active site. Docking analysis revealed strong binding affinity (ΔGbind = -7.91 kcal/mol) with stable hydrogen bonding to key residues. MD simulations, assessed via root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), radial distribution function (RDF), solvent-accessible surface area (SASA), dynamic cross-correlation maps (DCCM), and 2D principal component analysis (2D-PCA), confirmed ligand stability. MM-PBSA and per-residue decomposition analyses identified ARG43, TYR84, ASN87, LYS88, GLN132, GLY310, GLY313, and PRO314 as key contributors to ligand stabilization. These findings support 64Cu-ATSM as a potential MTHFD2-targeting theranostic agent. However, in vitro and in vivo studies are needed to validate its therapeutic efficacy, pharmacokinetics, and clinical relevance for hypoxia-selective cancer therapy.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3503-3521"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PM_2.5 Induced Vascular and Myocardial Calcification Impairs Ischemia-reperfusion Tolerance via Mitochondrial Dysregulation. PM2.5诱导的血管和心肌钙化通过线粒体失调损害缺血再灌注耐受性。

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-04-18 DOI: 10.1007/s12013-025-01758-7

Bhavana Sivakumar, Gino A Kurian

{"title":"PM2.5 Induced Vascular and Myocardial Calcification Impairs Ischemia-reperfusion Tolerance via Mitochondrial Dysregulation.","authors":"Bhavana Sivakumar, Gino A Kurian","doi":"10.1007/s12013-025-01758-7","DOIUrl":"10.1007/s12013-025-01758-7","url":null,"abstract":"Cardiovascular diseases (CVD) are intricately linked to vascular dysfunction, with growing evidence implicating particulate matter (PM2.5) as a major factor. This study addresses the urgent need to understand how PM2.5 exposure influences cardiac vulnerability to ischemia-reperfusion (IR) injury by investigating the underlying mechanisms of vascular and myocardial alterations. The aim was to assess the progressive impact of PM2.5 exposure on vascular and myocardial function, mainly focusing on mitochondrial integrity and calcification processes. Adult Wistar female rats were subjected to PM2.5 at a concentration of 250 µg/m3 for 3 h daily over 1, 7, 14, and 21 days. Cardiac endurance to IR injury was assessed using the Langendorff perfusion method. Findings revealed that exposure for 7 days or more induced vascular calcification, upregulating calcification-related genes and causing calcium accumulation, while endothelial dysfunction and impaired vascular contractility manifested earlier. Myocardial calcification and hemodynamic impairments became evident after 14 days, correlating with progressive mitochondrial dysfunction in both vascular and cardiac tissues. By day 21, severe mitochondrial damage and elevated cardiac sensitivity to IR injury were observed, accompanied by increased metal deposition in the vasculature and myocardium. The study concludes that PM2.5 exposure drives a cascade of vascular and myocardial alterations, with vascular dysfunction preceding myocardial calcification. These findings emphasize the need for strategies to mitigate PM2.5 induced cardiovascular risks, particularly by targeting mitochondrial health and vascular integrity.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3845-3858"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MiR-518b Promotes the Tumorigenesis of Hepatocellular Carcinoma by Targeting EGR1 to Regulate PI3K/AKT/mTOR Signaling Pathway. MiR-518b通过靶向EGR1调控PI3K/AKT/mTOR信号通路促进肝癌的发生。

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-04-13 DOI: 10.1007/s12013-025-01752-z

Xinyuan Wang, Juan Li, Jiao Nong, Xin Deng, Yiping Chen, Bing Han, Lin Zeng, Xiabing Huang

{"title":"MiR-518b Promotes the Tumorigenesis of Hepatocellular Carcinoma by Targeting EGR1 to Regulate PI3K/AKT/mTOR Signaling Pathway.","authors":"Xinyuan Wang, Juan Li, Jiao Nong, Xin Deng, Yiping Chen, Bing Han, Lin Zeng, Xiabing Huang","doi":"10.1007/s12013-025-01752-z","DOIUrl":"10.1007/s12013-025-01752-z","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a prevalent malignancy originating from hepatocytes and is characterized by high invasiveness and fatality. Dysregulation of microRNAs (miRNAs) is frequently observed during HCC progression. This study aimed to investigate the role of miR-518b in HCC cell malignancy and tumor growth. MiR-518b expression in HCC cells was measured by RT-qPCR. The proliferative, migratory and invasive capabilities of Hep3B and SNU-387 were assessed by colony formation, wound healing and transwell assays, respectively. RNA immunoprecipitation and luciferase reporter assays were utilized to verify the binding between miR-518b and its target gene, early growth response factor 1 (EGR1). Results revealed that miR-518b was highly expressed while EGR1 was downregulated in HCC cells. Knockdown of miR-518b significantly repressed cell proliferation, migration and invasion. Moreover, miR-518b bound to 3'untranslated region of EGR1 and negatively regulated its expression in HCC cells. EGR1 knockdown counteracted the inhibitory impact of miR-518b inhibition on malignant cell behaviors. In addition, the silencing of EGR1 activated the PI3K/AKT/mTOR signaling in HCC cells, while miR-518b depletion had the opposite effect. Importantly, the suppressive impact of miR-518b on the pathway was rescued by EGR1 knockdown. In vivo experiments demonstrated that inhibition of miR-518b suppressed HCC tumor growth, reduced EGR1 and Ki67 (a proliferation marker) expression, and inactivated the PI3K/AKT/mTOR signaling. In conclusion, miR-518b promotes HCC tumorigenesis by targeting EGR1 and regulating the PI3K/AKT/mTOR signaling pathway.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3759-3772"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selective Stabilization of LRRK2 Kinase Conformations Reveals Distinct Modes of Action for Type I and II Inhibitors. LRRK2激酶构象的选择性稳定揭示了I型和II型抑制剂的不同作用模式。

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 DOI: 10.1007/s12013-025-01877-1

Chuancheng Wei, Choon Han Heh, Sek Peng Chin

引用次数: 0

LncRNA BANCR/miR-15a/MAPK1 Induces Apoptosis and Increases Proliferation of Vascular Smooth Muscle Cells in Aortic Dissection by Enhancing MMP2 Expression. LncRNA BANCR/miR-15a/MAPK1通过增强MMP2表达诱导主动脉夹层血管平滑肌细胞凋亡和增殖

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-03-29 DOI: 10.1007/s12013-025-01738-x

Zihe Zheng, Wei Wang, Bo Chen, Ming Huang, Tao Wang, Zheng Xu, Xiaofu Dai

{"title":"LncRNA BANCR/miR-15a/MAPK1 Induces Apoptosis and Increases Proliferation of Vascular Smooth Muscle Cells in Aortic Dissection by Enhancing MMP2 Expression.","authors":"Zihe Zheng, Wei Wang, Bo Chen, Ming Huang, Tao Wang, Zheng Xu, Xiaofu Dai","doi":"10.1007/s12013-025-01738-x","DOIUrl":"10.1007/s12013-025-01738-x","url":null,"abstract":"Aortic dissection is associated with a high mortality rate, contributing to an unfavorable prognosis. Preventive measures are more effective than therapeutic interventions for aortic dissection. While LncRNA BANCR is recognized as a functional translational regulator in various diseases, its role in aortic dissection remains unexplored. This study aims to elucidate the functions and molecular mechanisms of BANCR in aortic dissection. Vascular smooth muscle cells were isolated from dissected aortic tunica media samples and their phenotypes were compared with those of commercial vascular smooth muscle cells. BANCR expression was modulated via transient transfection (overexpression) and small interfering RNA (knockdown). The involvement of the p38 MAPK pathway was examined using the inhibitor SB202190. The competing endogenous RNA network was validated through a dual luciferase assay. Cellular phenotypes were assessed using the CCK-8 assay, scratch assay, and flow cytometry. BANCR was overexpressed in dissected aortic tissues and isolated vascular smooth muscle cells. MiR-15a-5p exhibited binding affinity to both BANCR and MAPK1. Overexpression of BANCR activated p38 phosphorylation, enhanced cell proliferation and migration, and increased apoptosis. SB202190 mitigated these BANCR-induced phenotypes by inhibiting p38 phosphorylation. Additionally, MMP2 upregulation was linked to BANCR overexpression via the p38 MAPK pathway. Suppression of BANCR expression or inhibition of p38 phosphorylation reduced MMP2 levels, thereby reversing BANCR-induced phenotypes. The LncRNA BANCR/miR-15a-5p/MAPK1 axis forms a ceRNA network that modulates MMP2 expression through the p38 MAPK signaling pathway in vascular smooth muscle cells. BANCR overexpression activates p38 MAPK phosphorylation, leading to enhanced MMP2 expression and subsequent increases in cell proliferation, migration, and apoptosis.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3581-3596"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrative In-Silico Analysis of Retroperitoneal Tumors in Colorectal Surgery: Advancements and Implications. 结直肠手术腹膜后肿瘤的综合计算机分析：进展和意义。

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-04-16 DOI: 10.1007/s12013-025-01733-2

Wenqing Liu, Weida Chen, Maosheng Tang, Shibo Liu, Haichen Gao, Chengli Miao

{"title":"Integrative In-Silico Analysis of Retroperitoneal Tumors in Colorectal Surgery: Advancements and Implications.","authors":"Wenqing Liu, Weida Chen, Maosheng Tang, Shibo Liu, Haichen Gao, Chengli Miao","doi":"10.1007/s12013-025-01733-2","DOIUrl":"10.1007/s12013-025-01733-2","url":null,"abstract":"Retroperitoneal tumors pose significant challenges in colorectal surgery due to their complex anatomical location, aggressive behavior, and heterogeneous nature. Traditional diagnostic and treatment methods often fall short in effectively managing these tumors. This study leverages advanced in-silico methodologies to perform a comprehensive analysis of retroperitoneal tumors associated with colorectal conditions. By integrating computational modeling and cutting-edge bioinformatics tools, we aim to enhance the understanding of tumor biology, improve diagnostic precision, and optimize surgical outcomes. Our integrative approach combines transcriptomic, and proteomic data from publicly available databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Transcriptomic analysis reveals differentially expressed genes (DEGs) that serve as potential biomarkers for early diagnosis and prognosis. Proteomic analysis highlights critical protein interaction networks and pathways involved in tumorigenesis and metastasis. Our integrative approach identifies key DEGs and constructs protein-protein interaction (PPI) networks to pinpoint critical regulatory genes, such as VWF, PF4, ITGA2B, CXCL8, and GP9, that may serve as potential biomarkers or therapeutic targets. Functional enrichment analysis reveals significant pathways involved in tumorigenesis, including cell proliferation, immune response, and DNA repair. Additionally, immune cell infiltration analysis using the CIBERSORT algorithm demonstrates an immunosuppressive tumor microenvironment characterized by increased regulatory T cells (Tregs) and M2 macrophages, which could contribute to tumor immune evasion.Future studies should focus on clinical validation of these findings and the expansion of computational models to include diverse patient populations. Through these efforts, we aim to revolutionize the management of retroperitoneal tumors in colorectal surgery, ultimately improving patient care and survival rates.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3523-3533"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impaired Cellular Cholesterol Homeostasis Decreases Tumor-Derived Exosome Load And Modulates Malignant Transformation in Cancer Cells. 受损的细胞胆固醇稳态降低肿瘤源性外泌体负荷并调节癌细胞的恶性转化。

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-04-11 DOI: 10.1007/s12013-025-01744-z

Syed Sultan Beevi, Aishwarya Sudam Bhale, Vinod Kumar Verma, Radhika Chowdary Darapuneni

{"title":"Impaired Cellular Cholesterol Homeostasis Decreases Tumor-Derived Exosome Load And Modulates Malignant Transformation in Cancer Cells.","authors":"Syed Sultan Beevi, Aishwarya Sudam Bhale, Vinod Kumar Verma, Radhika Chowdary Darapuneni","doi":"10.1007/s12013-025-01744-z","DOIUrl":"10.1007/s12013-025-01744-z","url":null,"abstract":"Tumor-derived exosomes (TDEs) play a crucial role in horizontally transferring oncogenic information from tumors to other sites. Cellular cholesterol homeostasis has emerged as a significant factor influencing exosomal biogenesis and cellular release. In this study, we employed U18666A to induce cholesterol accumulation within the late endosomes of MDA-MB231 cells. We assessed the capacity of exosomes derived from U18666A-treated and untreated cells to initiate malignant transformation in HEK293 cells. Exosomes were isolated and characterized from both untreated and U18666A-treated MDA-MB231 cells, and HEK293 cells. The impact of exosomes derived from untreated MDA-MB231 cells (referred to as UCE) and U18666A-treated MDA-MB231 cells (referred to as UTCE) to induce transformation on HEK293 cells was investigated. Exosomes derived from MDA-MB231 cells induced proliferation, migration, malignant transformation, and epithelial-mesenchymal transition (EMT) process in HEK293 cells. Treatment with U18666A resulted in cholesterol accumulation within late endosomes, consequently markedly reversing the EMT process in MDA-MB231 cells. This treatment diminished the content of Tumor-derived exosomes released by the cancer cells, rendering them less oncogenic. This reduction in oncogenic potential was evident as they lost the ability to induce malignant transformation in recipient HEK293 cells. Modulating cholesterol homeostasis and disrupting the supply of cholesterol to aggressive cancer cells emerges as an appealing strategy to restrain the release of Tumor-derived exosomes and subsequently mitigate their contributory role in driving cancer progression and metastasis.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3651-3663"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating Network and Experimental Effect of Silibinin on Lipin-1 and Lipin-2 Gene Expression during Ischemia-reperfusion of the Liver in Rats. 水飞蓟宾对大鼠肝脏缺血再灌注过程中脂素-1、脂素-2基因表达的影响及网络研究

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-04-17 DOI: 10.1007/s12013-025-01751-0

Mahboubeh Ghanbari, Hossein Ebrahimi, Abouzar Bagheri, Abbas Khonakdar-Tarsi, Hadis Mousavi

{"title":"Investigating Network and Experimental Effect of Silibinin on Lipin-1 and Lipin-2 Gene Expression during Ischemia-reperfusion of the Liver in Rats.","authors":"Mahboubeh Ghanbari, Hossein Ebrahimi, Abouzar Bagheri, Abbas Khonakdar-Tarsi, Hadis Mousavi","doi":"10.1007/s12013-025-01751-0","DOIUrl":"10.1007/s12013-025-01751-0","url":null,"abstract":"This study aims to investigate the impact of silibinin (SILI) on the expression of the Lipin-1 and Lipin-2 genes during warm ischemia-reperfusion (I/R) of the liver. Network pharmacology was employed to identify potential targets of SILI in the context of liver inflammation and to elucidate the mechanism underlying the regulation of Lipin gene expression. The rats were allocated into four groups, each comprising eight individuals: vehicle group: These rats underwent a median laparotomy, and were administered normal saline. (2) SILI group: Rats in this group received 50 mg/kg of SILI after laparotomy. (3) I/R group: Rats in this group experienced I/R and were administered normal saline. (4) I/R+SILI group: In this group, rats were treated with SILI in conjunction with the I/R procedure. Western and real-time PCR were used to measure protein levels, and assess Lipin-1 and Lipin-2 gene expression. The analysis identified 18 shared targets between SILI (Severe Acute Liver Injury) and liver inflammation, linking them to 107 KEGG pathways, with the mTOR signaling pathway standing out as a critical connection to Lipin. Docking studies of targets in the mTOR signaling pathway revealed binding energies of -9.7 kcal/mol for PIK3CA and -10.4 kcal/mol for mTOR protein. Furthermore, the protein level and gene expression of Lipin-1 and Lipin-2 genes were significantly elevated during I/R compared to the vehicle group (P < 0.001). However, SILI was observed to reduce their expression during I/R (P < 0.05). The beneficial effects of SILI can be attributed to the modulation of Lipin-1 and Lipin-2 gene expression during I/R, which is likely one of the mechanisms underlying its beneficial effects during I/R.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3747-3758"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KPT-330, A New Candidate Drug for Targeting NOTCH1 Overexpression in T-cell Acute Lymphoblastic Leukemia, An In Vitro and Silico Study. 靶向NOTCH1过表达的t细胞急性淋巴细胞白血病新候选药物KPT-330的体外和计算机研究

IF 2.5 4区生物学

Cell Biochemistry and Biophysics Pub Date : 2025-09-01 Epub Date: 2025-04-11 DOI: 10.1007/s12013-025-01750-1

Fariha Naz, Saima Ejaz, Tayyaba Wali, Atiqa Nudrat, Mian Abdur Rehaman Arif, Muhammad Qandeel Waheed, Fatma Hussain, Saadiya Zia

{"title":"KPT-330, A New Candidate Drug for Targeting NOTCH1 Overexpression in T-cell Acute Lymphoblastic Leukemia, An In Vitro and Silico Study.","authors":"Fariha Naz, Saima Ejaz, Tayyaba Wali, Atiqa Nudrat, Mian Abdur Rehaman Arif, Muhammad Qandeel Waheed, Fatma Hussain, Saadiya Zia","doi":"10.1007/s12013-025-01750-1","DOIUrl":"10.1007/s12013-025-01750-1","url":null,"abstract":"B and T-lymphoid cancers usually originate from lymphoid progenitor cells. T-cell ALL, a subtype of acute lymphoblastic leukemia (ALL), arises due to unlimited and abnormal growth of blast cells. KPT-330, also known as Selinexor, prevents the transport of mRNAs and proteins from the nucleus to the cytoplasm by inhibiting the XPO1 transporter protein. The study aims to explore the NOTCH1 gene as a novel therapeutic target of KPT-330 in T-cell ALL by targeting the XPO1 protein. mRNA expression of the NOTCH1 gene was significantly elevated in T-cell ALL patients. The IC50 value of KPT330 for the Jurkat cells was determined by cell viability assay. The effect of KPT-330 on NOTCH1 gene expression in Jurkat cells was evaluated after 24, 48, and 72 h intervals. KPT-330 significantly downregulated the NOTCH1 gene expression at all time points in a dose-dependent manner. The molecular docking results revealed a binding affinity of -8.8 kcal/mol and identified GLU-140, LEU-141, and SER-144 as the potential amino acids of XPO1 forming a hydrogen bond with KPT-330. In silico analysis suggested the interaction of KPT-330 with the RNA-based NES_1 (UGUAUUAUU), NES_2 (UGUAUUUUU), and NES_3 (UUGUA) motifs in the 3' UTR of NOTCH1 mRNA resulting in NOTCH1 inhibition. Based on the results of in vitro and in silico studies, it was suggested that KPT-330 could be an ideal candidate drug for treating T-cell ALL patients with NOTCH1 overexpression.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"3731-3746"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0