Biochemical pharmacology最新文献

{"title":"Targeting YAP1-dependent aerobic glycolysis to mitigate fibrosis progression in morphea","authors":"Yiming Qin ,&nbsp;Yifei Lu ,&nbsp;Peng Yang ,&nbsp;Weiming Gou ,&nbsp;Yujia Yang ,&nbsp;Fei Wang ,&nbsp;Meijuan Xie ,&nbsp;Han Wang ,&nbsp;Yunchao Zhang ,&nbsp;Gaoxing Luo ,&nbsp;Qing Zhang ,&nbsp;Xiaoyan Lyu","doi":"10.1016/j.bcp.2025.117185","DOIUrl":"10.1016/j.bcp.2025.117185","url":null,"abstract":"<div><div>Morphea, a rare autoimmune disorder characterized by progressive skin fibrosis and soft tissue atrophy, remains clinically challenging due to poorly understood pathogenesis. Here, we revealed that mechanical abnormalities in morphea tissues activate the transcriptional co-activator Yes-associated protein 1 (YAP1), which drives pathological fibrosis through glycolytic reprogramming. Mechanistically, YAP1 promotes glycolysis by upregulating the expression of phosphofructokinase platelet type (PFKP), thus creating a self-reinforcing profibrotic cycle. Consequently, pharmacological inhibition of YAP1 with verteporfin (VP) significantly suppressed both transforming growth factor-beta 1 (TGF-β1)-induced glycolysis and fibrotic responses <em>in vitro</em>, while alleviating bleomycin-induced cutaneous fibrosis in murine models. Notably, VP demonstrated mitochondrial protective effects through dual modulation of fission machinery and PGC1α-mediated biogenesis pathway, further confirming its role in metabolic regulation. Collectively, these findings elucidate that YAP1-mediated metabolic dysregulation drives morphea progression and suggest that targeting YAP1 to modulate metabolic reprogramming represents a promising therapeutic strategy for this disease.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117185"},"PeriodicalIF":5.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681886","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":"The V-ATPase a3 subunit deficiency affects osteoarthritis via mTOR-Mediated autophagy levels in subchondral bone","authors":"Jianxin Qiu ,&nbsp;Xiaohang Zheng ,&nbsp;Jiajing Ye ,&nbsp;Tao Yang ,&nbsp;Xiaotong Wei ,&nbsp;Ting Jiang ,&nbsp;Yuhang Gong ,&nbsp;Zhenghua Hong ,&nbsp;Haixiao Chen ,&nbsp;Jie Xiang","doi":"10.1016/j.bcp.2025.117180","DOIUrl":"10.1016/j.bcp.2025.117180","url":null,"abstract":"<div><div>Autophagy is an evolutionarily conserved cellular self-degradation process that eliminates damaged organelles and misfolded proteins, thereby maintaining cellular homeostasis and delaying apoptosis and tissue degeneration. The efficient progression of autophagy depends on the maintenance of intracellular homeostasis, in which vacuolar ATPases (V-ATPases) play a crucial role by facilitating lysosomal acidification. Among these, the a3 subunit of V-ATPase, encoded by the T-cell immune regulator 1 (TCIRG1, also known as ATP6V0a3), is highly expressed in osteoclasts. However, its regulatory function in osteoarthritis (OA) remains largely unexplored. Our study found a reduction in TCIRG1 expression in the subchondral bone of OA patients and DMM (destabilization of the medial meniscus) mice. Additionally, TCIRG1 heterozygous knockout (HET) mice exhibited an abnormally thickened subchondral bone phenotype and impaired bone resorption. TCIRG1 is critical for lysosomal acidification and facilitates the completion of autophagy by promoting the fusion of late phagosomes with lysosomes. We further used rapamycin to restore partial autophagy and found that the treatment restored osteoclast resorption and also protected the articular cartilage matrix. Our findings demonstrate that TCIRG1 contributes to OA progression through regulation of autophagic activity. The results offer novel mechanistic insights into OA pathogenesis and support the potential of TCIRG1 as both a therapeutic target and a diagnostic biomarker.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117180"},"PeriodicalIF":5.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673884","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":"Pitavastatin overcomes multi-drug resistance in CRC and NSCLC by targeting the NRP1-ZFX axis","authors":"Yuan-yuan Zhai,&nbsp;Qiang Wang,&nbsp;Qi-yao Nong,&nbsp;Mei-yu Gao,&nbsp;Ying Zhang,&nbsp;Qin-wen Xiao,&nbsp;Yuan Tian,&nbsp;Zun-jian Zhang,&nbsp;Feng-guo Xu,&nbsp;Pei Zhang","doi":"10.1016/j.bcp.2025.117183","DOIUrl":"10.1016/j.bcp.2025.117183","url":null,"abstract":"<div><div>Multidrug resistance (MDR) is a significant challenge in cancer treatment, with limited effective strategies available. Neuropilin-1 (NRP1) is emerging as a potential therapeutic target for overcoming drug resistance, but its role in MDR and the identification of potential inhibitors require further exploration. In this study, we investigated the role of NRP1 in MDR and identifies potential inhibitors targeting NRP1. Elevated NRP1 expression was observed in oxaliplatin (OXP)-resistant HCT116 (HCT116/L) and cisplatin (DDP)-resistant A549 cells (A549/DDP). Virtual screening and biological assays identified pitavastatin (Ptv) as a potent NRP1 inhibitor that restored chemosensitivity in resistant cells both <em>in vitro</em> and <em>in vivo</em>. Mechanistic studies revealed that Ptv directly binds to NRP1, promotes degradation of Zinc finger X-chromosomal protein (ZFX), and disrupts the NRP1-ZFX axis to reverse MDR. This study provides promising prospects for targeting the NRP1-ZFX axis as a therapeutic strategy for MDR and highlights the potential clinical application of Ptv in diseases involving NRP1.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117183"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673881","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":"Running ameliorates methamphetamine-associated cognitive impairment by regulating hippocampal neurogenesis through the GSK3β/β-catenin pathway","authors":"Xu Zhao ,&nbsp;Chuanxiang Chen ,&nbsp;Jingyi Zhang ,&nbsp;Liang Zhang ,&nbsp;Cui Zhang ,&nbsp;Yining Zhang ,&nbsp;Feng Qiu ,&nbsp;Huijun Wang ,&nbsp;Jiancong Lu","doi":"10.1016/j.bcp.2025.117179","DOIUrl":"10.1016/j.bcp.2025.117179","url":null,"abstract":"<div><div>Physical exercise is a non-pharmacological therapy widely used in drug rehabilitation centers for treating methamphetamine (METH) addiction. METH causes cognitive impairment and suppresses adult hippocampal neurogenesis (AHN) in experimental animals. Exercise can improve cognitive dysfunction caused by various factors through the enhancement of AHN. However, little is known about the role of AHN and exercise in METH-induced neurotoxic injury. In this study, we aimed to investigate whether running could ameliorate METH-related cognitive impairment by promoting AHN in a low-dose METH addiction model and to uncover the underlying mechanisms. Behavioral experiments were conducted to assess changes in the behavior of mice. Immunofluorescence was used to analyze hippocampal neurogenic lineage, while Western blotting and qRT-PCR were employed to measure the expression levels of GSK3β/β-catenin and their downstream transcription factors. AAV-Nestin-Ctnnb1 was used to overexpress β-catenin in neural stem cells (NSCs). We found that low-dose METH induced cognitive impairment and decreased AHN without causing hippocampal cell death. Moreover, it reduced the proliferation and differentiation of NSCs in the dentate gyrus. Running ameliorated METH-related cognitive impairment by modulating AHN through the GSK3β/β-catenin pathway. Notably, overexpression of β-catenin in NSCs enhanced the expression of its downstream transcription factors, rescued AHN, and alleviated cognitive impairment. Our findings indicate that METH-induced cognitive impairment is linked to weakened AHN, and that running can effectively ameliorate METH-related cognitive dysfunction by enhancing AHN through the GSK3β/β-catenin pathway. Furthermore, these findings provide valuable insights into how exercise mitigates METH-related cognitive impairment and offer a theoretical basis for exercise-based therapies.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117179"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673882","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":"Targeting BACH1/PSPH axis suppresses bladder cancer progression and gemcitabine resistance by downregulating S100A2 expression","authors":"Tingxuan Ma ,&nbsp;Jing Ma ,&nbsp;Yipin Wang ,&nbsp;Xintong Kui ,&nbsp;Jiaxin Liu ,&nbsp;Chuanchun Han ,&nbsp;Wei Wei ,&nbsp;Zhikun Lin ,&nbsp;Xishuang Song","doi":"10.1016/j.bcp.2025.117182","DOIUrl":"10.1016/j.bcp.2025.117182","url":null,"abstract":"<div><div>Increasing evidence indicates that phosphoserine phosphatase (PSPH) promotes tumorigenesis in certain types of cancer. However, its specific role and regulatory mechanism in bladder cancer (BCa) remain unknown. In this study, we found that the expression level of PSPH is significantly upregulated in BCa tissues and patients with high PSPH levels exhibited shorter survival rates. Depletion of PSPH inhibited cell growth and metastatic potential of BCa cells. In contrast, upregulated PSPH promoted BCa progression and resistance to GEM. Mechanistically, increased PSPH enhanced the promoter activity of S100A2 and promoted S100A2 expression which led to malignant progression of BCa. The transcription factor BACH1 bound to the promoter of PSPH and facilitated PSPH expression in BCa. In addition, we also found that Brusatol directly bound to BACH1 and promoted BACH1 degradation. This study demonstrates the oncogenic role of PSPH in BCa and reveals that PSPH, upregulated by BACH1, promoted BCa progression and GEM resistance by elevating S100A2 expression. Brusatol acted as a novel inhibitor of BACH1 and suppressed malignance and GEM resistance of BCa by downregulating BACH1/PSPH/S100A2 pathway.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117182"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673883","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":"Triazine amine compounds synergistically enhance the efficacy against fluconazole-resistant Candida albicans with fluconazole by inhibiting cell wall synthesis","authors":"Luyi Jiang ,&nbsp;Mingxu Wang ,&nbsp;Lijiao Yang ,&nbsp;Bijuan Yang ,&nbsp;Liwei Xing ,&nbsp;Jingyu Liu ,&nbsp;Runcheng Yan ,&nbsp;Jin Han ,&nbsp;Ganpeng Li ,&nbsp;Ruirui Wang","doi":"10.1016/j.bcp.2025.117181","DOIUrl":"10.1016/j.bcp.2025.117181","url":null,"abstract":"<div><div>Invasive fungal infections caused by <em>Candida albicans</em> are associated with high morbidity and mortality, highlighting the urgent need for novel antifungal agents. Compound 2 m in combination with fluconazole exhibited a significant synergistic effect (fractional inhibitory concentration index range: 0.15–0.17) and demonstrated enhanced efficacy against fluconazole-resistant strains. The combination therapy inhibited hyphal growth and biofilm formation, promoted the exposure of cell wall components, and disrupted cell membrane integrity. Transmission electron microscopy confirmed damage to cellular structures. The mechanism of action may be related to the downregulation of cell wall synthesis related genes (<em>WSC1</em>, <em>WSC2</em>, and <em>FKS1</em>) to inhibit <em>C. albicans</em> activity. This combination therapy reduced the renal fungal burden and inflammation <em>in vivo</em>, improved survival, and restored immune function. Additionally, compound 2 m demonstrated low cytotoxicity, suggesting its potential as an antimicrobial enhancer for fluconazole, and augmenting its inhibitory effect against fungal strains through synergistic effects, thereby offering a novel strategic approach for antifungal therapy.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117181"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673885","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 “PCSK9 inhibition mitigates vulnerable plaque formation induced by hyperhomocysteinemia through regulating lipid metabolism and inflammation” [Biochem. Pharmacol. 239 (2025) 117031]","authors":"Ping Jin ,&nbsp;Juan Ma ,&nbsp;Peng Wu ,&nbsp;Ru Yan ,&nbsp;Yitong Bian ,&nbsp;Shaobin Jia ,&nbsp;Qiangsun Zheng ,&nbsp;Xueping Ma","doi":"10.1016/j.bcp.2025.117137","DOIUrl":"10.1016/j.bcp.2025.117137","url":null,"abstract":"","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117137"},"PeriodicalIF":5.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653014","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":"Targeting STING alleviates pyroptosis of bladder epithelial cells and ameliorates bladder fibrosis in neurogenic bladder","authors":"Runchang Wang ,&nbsp;Mingxin Wang ,&nbsp;Jing Chen ,&nbsp;Miao Sun ,&nbsp;Peng Zhao ,&nbsp;Xiangqin Zheng ,&nbsp;Dinggang Li ,&nbsp;Chunlan Long ,&nbsp;Lianju Shen ,&nbsp;Guanghui Wei ,&nbsp;Shengde Wu","doi":"10.1016/j.bcp.2025.117177","DOIUrl":"10.1016/j.bcp.2025.117177","url":null,"abstract":"<div><div>Neurogenic bladder (NB) is a common urinary system disease in children and often accompanied by bladder inflammation and fibrosis. Currently, NB has very few treatment options. Stimulator of interferon genes (STING) links immune response with inflammatory processes and is associated with the development of diverse fibrotic diseases. However, the regulatory role of STING in NB-induced bladder fibrosis remains unclear. In this study, we established the NB rat model by transecting the L6-S1 spinal nerves. RNA sequencing and correlation analysis indicated that activation of the cGAS-STING pathway and the pyroptosis related NLRP3 pathway occurred in the fibrotic bladder. Further research indicated that after STING activation, it would activate downstream targets such as interferon regulatory transcription factor 3 (IRF3) and NF-κB, induce pyroptosis in bladder epithelial cells, and ultimately lead to the generation of pro-inflammatory and fibrotic factors. Intravesical C-176 (a STING inhibitor) treatment remarkably decreased the collagen content and improved bladder function. In addition, our study also elucidated that MFN2 affected the release of mtDNA by binding to BAX and regulated the cGAS-STING pathway. In conclusion, our research verified that the MFN2-BAX/cGAS-STING/NLRP3 axis as a critical driver of NB-induced bladder fibrosis. Targeting STING provides a novel therapeutic strategy to reduce inflammation and fibrosis, with potential clinical applications for NB management.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117177"},"PeriodicalIF":5.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663362","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":"DNA damage agents trigger iNKT cell-mediated elimination of AML cells through activation of NF-κB/HLA-DRB6/CD1d pathway","authors":"Guihui Tu ,&nbsp;Qiurong Wu ,&nbsp;Yuxia Yuan ,&nbsp;Qingna Jiang ,&nbsp;Yuanling Tang ,&nbsp;Xinhua Wu ,&nbsp;Yiling Lu ,&nbsp;Junjin Lin ,&nbsp;Zhengmian Zhang ,&nbsp;Lixian Wu","doi":"10.1016/j.bcp.2025.117174","DOIUrl":"10.1016/j.bcp.2025.117174","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is the most common and deadly type of leukemia with the high recurrence rates and poor prognosis. Despite extensive exploration of therapeutic strategies, there is currently no effective remedy for AML. Recently, there has been a growing focus on immunotherapeutic approaches for treating hematologic malignancies. CD1d-restricted invariant Natural Killer T (iNKT) cells have been recognized for their significant role in antitumor immunity. This study identified a potential therapeutic strategy based on the iNKT cells and demonstrated that treating AML cells with DNA damage agents can enhance iNKT cell-mediated cytotoxicity <em>in vitro</em>. Research has also demonstrated that DNA damage regulates CD1d gene transcription activity by specifically activating NF-κB/RELA. Additionally, lncRNA-HLA-DRB6 is involved in the targeted regulation of CD1d by RELA, thus promoting the stability of CD1d mRNA in the cytoplasm. The activation of the RELA/lncRNA-HLA-DRB6/CD1d pathway by DNA damage contributes to sensitizing AML cells to killing by iNKT cells. Furthermore, combination treatment with α-galactosylceramide (α-GalCer; which is an activator of iNKT cells) and DNA damage agents exhibited synergistic antitumor effects <em>in vivo</em>, which may be beneficial for alleviating the progression of AML. In conclusion, these findings provide information on the mechanism by which DNA damage in AML cells regulates iNKT cell activity, thus suggesting that the development of immune therapeutic strategies based on iNKT cells during chemotherapy may represent a potential avenue for AML treatment.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117174"},"PeriodicalIF":5.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666979","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":"Impact of bradykinin type 2 receptor overexpression on cardiovascular function in mice","authors":"Sara Metry ,&nbsp;Tatsiana Suvorava ,&nbsp;Jens W. Fischer ,&nbsp;Vu Thao-Vi Dao ,&nbsp;Georg Kojda","doi":"10.1016/j.bcp.2025.117175","DOIUrl":"10.1016/j.bcp.2025.117175","url":null,"abstract":"<div><div>Bradykinin is an endogenous peptide playing an important role in regulation of vascular function and permeability, but cardiovascular effects of endogenous bradykinin remain incompletely understood. We studied whether genetically engineered overexpression of endothelial bradykinin type 2 receptor (B₂) alters cardiac and vascular function using mice with endothelial-specific overexpression of B₂ (B₂^tg) and their transgene-negative littermates (B₂ⁿ). In the aorta, brain-stem and skeletal muscle of B₂^tg human BDKRB2 were exclusively expressed, and B₂-overexpression was evident by a significant upregulation of B₂ protein. Endothelium-dependent aortic relaxation and responses to phenylephrine or the nitric oxide (NO) donor measured <em>ex vivo</em> were unaffected by the transgene. In contrast, bradykinin induced constriction in B₂ⁿ, but i vasorelaxation in B₂^tg that was sensitive to inhibition of NO-synthase (NOS). <em>In vivo</em> assessment of endothelial function by flow-mediated dilation revealed no changes in B₂^tg as compared to B₂ⁿ. Likewise, transthoracic echocardiography showed no effect of B₂ overexpression on cardiac function. In contrast, decreased systolic blood pressure and bradycardia were observed in B₂^tg. The decrease in blood pressure in B₂^tg remained following inhibition of cyclooxygenase and NOS, but was completely abolished by the selective B₂ antagonist icatibant. Thus, endothelial-specific B₂-overexpression induced mild hypotension and bradycardia while having no effect on flow-mediated dilation or several cardiac function parameters. These minor effects of endothelial-specific B₂ overexpression in healthy mice suggest that alterations of endogenous bradykinin generation may not be associated with derangements of cardiovascular functions, however, the long-term safety of continuous changes of bradykinin in cardiovascular comorbidities deserves further rigorous clinical investigation.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"241 ","pages":"Article 117175"},"PeriodicalIF":5.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666980","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}