Life sciences最新文献

{"title":"Toxicological profiling and diuretic potential of arbutin via aldosterone synthase gene inhibition","authors":"Maria Nazeer MS ,&nbsp;Nabi Shah PhD ,&nbsp;Saif Ullah MS ,&nbsp;Muhammad Ikram PhD ,&nbsp;Muhammad Imran Amirzada PhD ,&nbsp;Abdulmohsin J. Alamoudi PhD ,&nbsp;Meshal Alshamrani PhD ,&nbsp;Abdul Jabbar Shah PhD","doi":"10.1016/j.lfs.2025.123661","DOIUrl":"10.1016/j.lfs.2025.123661","url":null,"abstract":"<div><h3>Aims</h3><div>Arbutin (ARB), a natural polyphenol isolated from the bearberry plant <em>Arctostaphylos uva-ursi</em>, has been studied for its diverse pharmacological activities including anti-diabetic, cardioprotective and anti-inflammatory effects. This study aimed to evaluate arbutin’s diuretic activity, focusing on its impact on aldosterone synthase gene expression and its toxicity profile.</div></div><div><h3>Material and methods</h3><div>Acute toxicity was assessed using single doses ranging from 500 to 9000 mg/kg and sub-acute toxicity with doses of 375 and 750 mg/kg over 14 days. To evaluate acute diuretic activity, ARB was administered in three doses (25, 50 and 75 mg/kg i.p) alongside standard groups, furosemide (FUR) 10 mg/kg i.p and Spironolactone (SPIR) 25 mg/kg i.p. In sub-acute diuretic study, treatment was administered for seven days, followed by blood collection and adrenal dissection for gene expression analysis.</div></div><div><h3>Key findings</h3><div>Acute toxicity studies revealed that ARB is well-tolerated up to 7000 mg/kg with no significant changes in organ and body weight. However, sub-acute studies showed minor changes in leukocyte count, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and triglycerides (TGs) at high doses while histopathological evaluations revealed no severe organ damage. The diuretic index and electrolyte analysis confirmed the potential of ARB as diuretic and saluretic with reduced risk of hyperuricemia and hyperkalemia. Gene expression studies showed non-selective downregulation of aldosterone synthase gene (CYP11B2) and 11β-hydroxylase (CYP11B1). While the effects on 17α-hydroxylase (CYP17A1) were less pronounced than SPIR, indicating fewer possible anti-androgenic effects.</div></div><div><h3>Significance</h3><div>Our findings suggest that ARB is a promising diuretic agent with a favorable safety profile.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"373 ","pages":"Article 123661"},"PeriodicalIF":5.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-therapy with S1P and heparan sulfate derivatives to restore endothelial glycocalyx and combat pro-atherosclerotic endothelial dysfunction.","authors":"Ronodeep Mitra, Kaleigh Pentland, Svilen Kolev, Matthew Eden, Erel Levine, Jessica M Oakes, Eno E Ebong","doi":"10.1016/j.lfs.2025.123662","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123662","url":null,"abstract":"<p><strong>Aims: </strong>Endothelial cell (EC) glycocalyx (GCX) shedding from disturbed blood flow and chemical factors leads to low-density lipoprotein infiltration, reduced nitric oxide synthesis, vascular dysfunction and atherosclerosis. This study evaluates a therapy combining sphingosine-1-phosphate (S1P) and heparin (heparan sulfate derivative). We hypothesized that heparin/S1P co-treatment repairs mechanically damaged EC GCX in disturbed flow (DF) regions and restores anti-atherosclerotic mechanotransduction to treat cardiovascular disease.</p><p><strong>Materials and methods: </strong>We used a parallel-plate flow chamber to simulate flow conditions in vitro and a partial carotid ligation mouse model to mimic DF in vivo. Heparin and albumin-bound S1P were administered to assess their reparative effects on the endothelial GCX. Fluorescent staining, confocal microscopy, and ultrasound evaluated endothelial cell function and endothelial-dependent vascular function. Barrier functionality was assessed via macrophage uptake. Heparin/S1P mechanism-of-action insights were gained through fluid dynamics simulations and staining of GCX synthesis enzyme and S1P receptor. Statistical analyses validated the results.</p><p><strong>Key findings: </strong>The in vitro data showed that heparin/S1P therapy improves DF-conditioned ECs by restoring GCX and elevating vasodilator eNOS (endothelial-type nitric oxide synthase) expression. In vivo studies confirmed GCX degradation, vessel inflammation, hyperpermeability, and wall thickening in the mouse model's partially ligated left carotid artery. Heparin/S1P treatment restored GCX thickness and coverage, reduced inflammation and hyperpermeability, and inhibited vessel wall thickening.</p><p><strong>Significance: </strong>This work introduces a new approach to regenerating the EC GCX and restoring its function in ECs under DF conditions, offering a groundbreaking solution for preventing cardiovascular diseases like atherosclerosis.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123662"},"PeriodicalIF":5.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A signpost to guide the key therapeutic components of Aralia continentalis Kitag roots in treating T2DM-derived heart attack, and diabetic nephropathy via systems biology concept","authors":"Ki-Kwang Oh ,&nbsp;Seol Hee Song,&nbsp;Jeong Ha Park ,&nbsp;Min Ju Kim,&nbsp;Dong Joon Kim,&nbsp;Ki-Tae Suk","doi":"10.1016/j.lfs.2025.123635","DOIUrl":"10.1016/j.lfs.2025.123635","url":null,"abstract":"<div><h3>Aims</h3><div><em>Aralia continentalis</em> Kitag roots (ACKRs) have been regarded as a nutritional natural resource for treating different diseases, including type 2 diabetes mellitus (T2DM), and its complications (heart attack; HA, diabetic nephropathy; DN). Nonetheless, an extensive investigation of T2DM-derived complications has yet to be performed.</div></div><div><h3>Main methods</h3><div>Accordingly, we adopted gas chromatography–mass spectrometry (GC–MS) to identify the molecules of ACKRs, followed by the use of cheminformatics (Similarity Ensemble Approach; SEA, SwissTargetPrediction; STP), bioinformatics (STRING, DisGeNET, and OMIM), and computer screening tools to investigate its corresponding targets, in T2DM diseases and its complications.</div></div><div><h3>Key findings</h3><div>The primary targets (PPARG, and IL6) were confirmed via a protein–protein interaction (PPI) network, suggesting that IL6- Andrographolide, PPARA-Germacrene D, PPARD- Kaurenoic acid, PPARG- Kaurenoic acid, NR1H3- 1-Naphthalenepropanol, α-ethenyldecahydro-5-(hydroxymethyl)-α,2,5,5,8a-pentamethyl-, and FABP4- Kaurenoic acid conformers on PPAR signaling pathway might exert agonistic mode.</div></div><div><h3>Significance</h3><div>These findings underline that ACKRs' bioactives filtered by the devised platform could prevent T2DM-derived complications through multiple-target.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123635"},"PeriodicalIF":5.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine-modified circQKI inhibits prostate cancer docetaxel-sensitivity via miR-188-3p/Beclin-1 pathway","authors":"Tong Zhao ,&nbsp;Kai Li ,&nbsp;Yetao Zhang ,&nbsp;Yuxiang Dong ,&nbsp;Yongshan Li ,&nbsp;Mingyang Pang ,&nbsp;Yong Wei ,&nbsp;Bing Yao ,&nbsp;Qingyi Zhu","doi":"10.1016/j.lfs.2025.123646","DOIUrl":"10.1016/j.lfs.2025.123646","url":null,"abstract":"<div><h3>Background</h3><div>Docetaxel (DTX) is used in the first-line chemotherapy for advanced castration-resistant prostate cancer (CRPC), but resistance remains a major clinical challenge. Circular RNAs (circRNAs) play critical roles in DTX resistance. This study aimed to investigate the mechanism of a novel circRNA, circQKI, in DTX resistance and its regulatory network in CRPC.</div></div><div><h3>Methods</h3><div>DTX-resistant cell lines (PC3/DR and 22RV1/DR) were established, and circQKI's circular structure was validated by Sanger sequencing. CircQKI expression was modulated via siRNA knockdown and overexpression plasmids. Cell viability, apoptosis, and colony formation were assessed by CCK-8, flow cytometry, and clonogenic assays. The interaction between circQKI and miR-188-3p was verified by dual-luciferase reporter, RIP, and RNA pull-down. Autophagy activation was analyzed via Western blot and TEM. Subcutaneous xenograft models evaluated in vivo drug resistance. M6A modification was investigated through m6A RIP-PCR, METTL3/IGF2BP2 knockdown, and stability assays.</div></div><div><h3>Results</h3><div>CircQKI was significantly upregulated in resistant cells and promoted DTX resistance by sponging miR-188-3p, thereby enhancing Beclin-1 expression and autophagy activation. Inhibiting Beclin-1 or co-treatment with chloroquine (CQ) partially restored DTX sensitivity. Mechanistically, METTL3-mediated m6A modification stabilized circQKI via IGF2BP2 recognition, leading to its accumulation in resistant cells. In vivo studies confirmed that circQKI overexpression reduced tumor sensitivity to DTX by enhancing autophagy.</div></div><div><h3>Conclusion</h3><div>circQKI drives DTX resistance via the miR-188-3p/Beclin-1 axis and autophagy activation, with its expression regulated by METTL3-dependent m6A modification and IGF2BP2. Targeting circQKI or autophagy pathways may offer novel therapeutic strategies to overcome DTX resistance in prostate cancer.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123646"},"PeriodicalIF":5.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Translocator protein 18 kDa ligand alleviates neointimal hyperplasia in the diabetic rat artery injury model via activating PKG” [Life. Sci. 221 (2019) 72–82]","authors":"Zhengfan Gong ,&nbsp;Yu Han ,&nbsp;Lianpan Wu ,&nbsp;Tianyang Xia ,&nbsp;Hongmei Ren ,&nbsp;Donghai Yang ,&nbsp;Daqian Gu ,&nbsp;He Wang ,&nbsp;Cuimei Hu ,&nbsp;Duofen He ,&nbsp;Lin Zhou ,&nbsp;Chunyu Zeng","doi":"10.1016/j.lfs.2025.123629","DOIUrl":"10.1016/j.lfs.2025.123629","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123629"},"PeriodicalIF":5.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnesium-based implants accelerate femoral fracture healing through promoting histone lactylation-mediated osteoclastogenesis inhibition","authors":"Junyi Shen ,&nbsp;Yilun Pei ,&nbsp;Shangying Bai ,&nbsp;Simeng Lei ,&nbsp;Suhang Xia ,&nbsp;Jie Zhang ,&nbsp;Xingyu Li ,&nbsp;Hanchi Xu ,&nbsp;Xinyu Zheng ,&nbsp;Xuezhen Shen ,&nbsp;Huanjun Zhao ,&nbsp;Liang Liu ,&nbsp;Xinlin Yang ,&nbsp;Xuefei Wang","doi":"10.1016/j.lfs.2025.123639","DOIUrl":"10.1016/j.lfs.2025.123639","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the molecular mechanisms by which magnesium (Mg)-based implants, specifically Mg-containing intramedullary nails (Mg-IMNs), promote femoral fracture healing.</div></div><div><h3>Materials and methods</h3><div>Rats with femoral fractures were treated with Mg-IMNs. In vitro experiments were conducted to assess the impact of Mg²⁺ on osteoclastogenesis and histone lactylation. Histological analysis, Western blotting, and qRT-PCR were employed to evaluate osteoclast maturation and the molecular pathways involved. In vivo, lactate was administered to replicate Mg-IMN effects, and lactate production was inhibited to observe potential reversal effects.</div></div><div><h3>Key findings</h3><div>Mg-IMNs significantly enhanced fracture healing by inhibiting osteoclastogenesis. Mg²⁺ promoted intracellular lactate production, leading to histone lactylation, which suppressed osteoclast maturation by downregulating NFATc1. The P300/H3K18LA/HDAC1 pathway was identified as a key mediator in this process. Additionally, lactate administration mimicked the effects of Mg-IMNs, while blocking lactate reversed these effects.</div></div><div><h3>Significance</h3><div>This study uncovers a novel mechanism by which Mg²⁺ promotes fracture healing through histone lactylation-mediated inhibition of osteoclastogenesis. These findings offer new therapeutic strategies for enhancing fracture repair via epigenetic regulation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123639"},"PeriodicalIF":5.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ARID3A inhibits colorectal cancer cell stemness and drug-resistance by targeting a multitude of stemness-associated genes","authors":"Tamal Kanti Gope ,&nbsp;Debankur Pal ,&nbsp;Amit Kumar Srivastava ,&nbsp;Bilash Chatterjee ,&nbsp;Subhankar Bose ,&nbsp;Rupasri Ain","doi":"10.1016/j.lfs.2025.123642","DOIUrl":"10.1016/j.lfs.2025.123642","url":null,"abstract":"<div><h3>Aims</h3><div>ARID3A is highly expressed in CRC patients. However, the functional role of ARID3A in CRC remains unexplored. We sought to demonstrate ARID3A function in CRC.</div></div><div><h3>Materials and methods</h3><div>ARID3A was knocked-down using lentiviruses harboring shRNA. CRC patients' tissue cDNA array was used to assess expression of ARID3A. Effect of ARID3A on CSC-associated genes was analysed using real-time PCR array. Western-blot analysis and ChIP assay were used to validate the role of ARID3A. Paclitaxel-resistant CSC-enriched cell population was used to assess correlation between ARID3A, stemness and drug resistance potential. <em>Ex vivo</em> findings were corroborated on preclinical mouse model.</div></div><div><h3>Key findings</h3><div>ARID3A expression was significantly higher throughout CRC stages than normal individuals. ARID3A expression was significantly higher in the aggressive CRC cell line HCT116 compared to HT29, which expressed higher levels of CD44, CD133, and EpCAM, suggesting a reciprocal relationship between ARID3A expression and CRC stemness. Real-time PCR-based stem cell array using ARID3A-knockdown HCT116 cells showed upregulation of 9 cancer stem cell (CSC)-associated genes. ChIP-assay verified binding of ARID3A on transcriptionally active promoter regions of CSC associated genes. ARID3A depletion led to enhanced proliferation, anchorage-independent growth, and ABCG2 upregulation in HCT116 cells. In paclitaxel-resistant HCT116 cells, ARID3A expression was dampened, whereas, CD44 and CD133 increased. ARID3A knockdown accelerated tumor growth and promoted larger tumor formation in nude-mouse xenograft model. Ki67, CD44 and CD133 were highly upregulated in knockdown tumors.</div></div><div><h3>Significance</h3><div>This study demonstrated that ARID3A inhibits CRC stemness, anchorage-independent growth, self-renewal, anti-cancer drug resistance of CRC cells and tumor growth <em>in vivo</em>.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123642"},"PeriodicalIF":5.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Decoding proteomic cross-talk between hypobaric and normobaric hypoxia: Integrative analysis of oxidative stress, cytoskeleton remodeling, and inflammatory pathways” [Life Sci. 371 (2025) 123611]","authors":"Poornima Sharma,&nbsp;Swaraj Mohanty,&nbsp;Yasmin Ahmad","doi":"10.1016/j.lfs.2025.123636","DOIUrl":"10.1016/j.lfs.2025.123636","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123636"},"PeriodicalIF":5.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel tubulin inhibitor, No.07, shows anti-cancer and anti-metastatic effects in colon cancer and tumoroids","authors":"Ho Jin Han ,&nbsp;Junyeol Han ,&nbsp;Yerim Choi ,&nbsp;Gwi-Ja Hwang ,&nbsp;Sumin Kim ,&nbsp;In-Ja Ryoo ,&nbsp;Bo Yeon Kim ,&nbsp;Nak-Kyun Soung","doi":"10.1016/j.lfs.2025.123644","DOIUrl":"10.1016/j.lfs.2025.123644","url":null,"abstract":"<div><div>Colorectal cancer is a highly metastatic disease and the second leading cause of cancer-related death worldwide. Despite the use of various treatment strategies, including chemotherapy and targeted therapy, challenges such as toxicity, drug resistance, and poor response indicate the critical need for new therapeutic agents.</div><div>Microtubule target agents are one of the major treatment options for chemotherapy in various cancer patients. However, most of these agents are substrates of the MDR1 protein, which leads to the development of multidrug resistance, significantly limiting their effectiveness. Therefore, the development of new drugs is being actively pursued.</div><div>In this study, we synthesized a novel compound, No.07, which demonstrates significant anti-cancer activity in 3D spheroid models, patient-derived colon cancer organoid models, and mice xenograft models. No.07 directly binds to tubulin dimers, interfering with microtubule polymerization and thereby disrupting tubulin dynamics, ultimately inducing mitotic arrest. Furthermore, No.07 increases mitochondria reactive oxygen species level, leading to the inactivation of the RAF-MEK-ERK signaling cascade, which consequently inhibits metastasis. Notably, Swiss ADME predictions suggest that No.07 is not a substrate of MDR1 and can cross the blood-brain barrier, unlike other microtubule target agents that are limited by MDR1-mediated drug resistance and poor brain penetration. Additionally, experiments using multidrug-resistant cell lines confirmed that No.07 effectively overcomes multidrug resistance, providing a significant improvement over traditionally used chemotherapy agents. In conclusion, No.07 has the potential to address the limitations of existing treatments as a novel therapeutic option.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123644"},"PeriodicalIF":5.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional and post-translational mechanisms of ECM remodeling in rotator cuff tendons under hyperlipidemic conditions","authors":"Resmi Rajalekshmi,&nbsp;Devendra K. Agrawal","doi":"10.1016/j.lfs.2025.123647","DOIUrl":"10.1016/j.lfs.2025.123647","url":null,"abstract":"<div><div>Rotator cuff injuries present significant clinical challenges, often resulting in chronic pain and functional impairment. In this study, we examined the effects of hyperlipidemia (HYP), a systemic metabolic condition, on tendon health. Histological analysis of infraspinatus tendons from hyperlipidemic swine revealed well-organized extracellular matrix (ECM) structures, comparable to those in non-hyperlipidemic (NONHYP) animals, suggesting ECM reorganization. Upstream SIGNOR3.0 analysis demonstrated that tumor necrosis factor receptor-associated factor 6 (TRAF6) activates transcription factor Yin Yang 1 (YY1) via kinase signaling, underscoring its role in tendon ECM remodeling. Hence, we futher examined the role of YY1, which is a critical regulator of collagen synthesis identified through network analysis. Although TRAF6 levels remained unchanged in HYP conditions, increased YY1 expression correlated with elevated COL1 gene expression. Additionally, twist-related protein 1 (TWIST1) emerged as another key molecule, existing in both homo- and heterodimer forms in NON-HYP conditions, but only as a heterodimer in HYP. YY1 enhanced COL1 transcription in the hyperlipidemic environment, while TWIST1 heterodimer formation facilitated collagen crosslinking. Notably, increased YY1 expression inhibited MMP3, resulting in the inactivity of MMP1, MMP8, and MMP9, thereby preserving collagen levels. These findings highlight the complex molecular interactions involving transcriptional regulation by YY1 and post-translational regulation by the TWIST1 heterodimer, essential for the deposition of mature collagen fibrils and driving tendon remodeling in hyperlipidemic conditions. This study offers valuable insights for the change of tendon health condition in hyperlipidemia disease or tendon pathology.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123647"},"PeriodicalIF":5.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}