Molecular and Cellular Biochemistry最新文献

{"title":"Single-cell atlas profiling revealed cellular characteristics and dynamic changes after PD-1 blockade therapy of brain metastases from laryngeal squamous cell carcinoma.","authors":"Yunzhi Zou, Hao Duan, Zekun Deng, Rong Xiang, Jixiang Zhao, Zhenhua Zhang, Wanming Hu, Yuanzhong Yang, Zeming Yan, Shujuan Wen, Zexian Liu, Gao Zhang, Yonggao Mou, Depei Li, Xiaobing Jiang","doi":"10.1007/s11010-024-05064-3","DOIUrl":"10.1007/s11010-024-05064-3","url":null,"abstract":"<p><p>Brain metastasis (BM) in laryngeal squamous cell carcinoma (LSCC) is uncommon but prognosis is poor. Anti-PD-1 immunotherapy benefits some advanced LSCC cases, yet its efficiency is limited by tumor complexity. We analyzed paired metastatic tumor samples from before and after immunotherapy using single-cell RNA sequencing (scRNA-seq), along with a primary LSCC dataset and bulk RNA sequencing. This identified changes post-immunotherapy and revealed differences in single-cell transcriptomes among LSCC, primBM, and neoBM. Our findings show that anti-PD-1 treatment suppresses metastasis-promoting pathways like VEGF and EMT in cancer cells, and alters immune cell functions. Notably, it upregulates T cell activation, leading to CD8 T cell exhaustion from excess heat shock proteins, notably HSPA8. However, CD8 T cell cytotoxic functions improve post-treatment. In myeloid cells, anti-PD-1 therapy enhances antigen presentation and promotes a proinflammatory shift post-metastasis. Additionally, NUPR1 is linked to BM in LSCC, and NEAT1 is a potential metastatic cancer cell cycle participant. Our study provides insights into cancer heterogeneity and the impact of PD-1 immunotherapy on metastasis, aiding precise diagnosis and prognosis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2377-2400"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelium Piezo1 deletion alleviates experimental varicose veins by attenuating perivenous inflammation.","authors":"Jiani Zhao, Yacheng Xiong, Yu Liu, Jin Ling, Shuai Liu, Wei Wang","doi":"10.1007/s11010-024-05115-9","DOIUrl":"10.1007/s11010-024-05115-9","url":null,"abstract":"<p><p>Previous large-scale genetic studies have prioritized the causal genes piezo type mechanosensitive ion channel component 1 (PIEZO1) and castor zinc finger 1 (CASZ1) associated with varicose veins (VVs). This study aims to evaluate their roles in both clinical and experimental VVs. In this study, we investigated abundance of PIEZO1 and CASZ1 in both varicose and normal veins from the same patients. Yoda1 (a selective PIEZO1 agonist, 2.6 mg/kg/day) or vehicle was administered intraperitoneally for 3 weeks to evaluate the effect of PIEZO1 activation on experimental VVs. Subsequently, endothelial Piezo1 deletion mice (Piezo1^iΔEC mice) were generated to explored the role of endothelial PIEZO1 on VVs. Laser speckle imaging, flow cytometry, cell tracing with Evans blue or rhodamine-6G, and histopathological staining were utilized to evaluate the pathophysiology of VVs. Our results showed that mRNA expression of PIEZO1, but not CASZ1, was abundant and increased in clinical VVs. The Piezo1^tP1-td mice revealed endothelium-specific expression of PIEZO1 in mice veins. By establishing iliac vein ligation-induced VVs in mice, Yoda1 exacerbated experimental VVs with increased inflammatory cell infiltration. Subsequently, endothelial Piezo1 deletion (Piezo1^iΔEC mice) alleviated experimental VVs and vascular remodeling by directly reducing vascular permeability and leukocyte-endothelium interactions compared to the control (Piezo1^fl/fl mice). PIEZO1 is highly expressed in clinical VVs, meanwhile, activation or inhibition of PIEZO1 exerts a remarkable effect on experimental VVs. Furthermore, Piezo1 may constitute a potential therapeutic approach for the medical treatment of VVs.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2423-2435"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Swertiamarin relieves radiation-induced intestinal injury by limiting DNA damage.","authors":"Zhe Zhao, Dan He, Jinyu Wang, Yu Xiao, Lixin Gong, Can Tang, Haibo Peng, Xuemei Qiu, Rui Liu, Tao Zhang, Jingyi Li","doi":"10.1007/s11010-024-05030-z","DOIUrl":"10.1007/s11010-024-05030-z","url":null,"abstract":"<p><p>Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2277-2290"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving effect of physical exercise on heart failure: Reducing oxidative stress-induced inflammation by restoring Ca²⁺ homeostasis.","authors":"Shunling Yuan, Zhongkai Kuai, Fei Zhao, Diqun Xu, Weijia Wu","doi":"10.1007/s11010-024-05124-8","DOIUrl":"10.1007/s11010-024-05124-8","url":null,"abstract":"<p><p>Heart failure (HF) is associated with the occurrence of mitochondrial dysfunction. ATP produced by mitochondria through the tricarboxylic acid cycle is the main source of energy for the heart. Excessive release of Ca²⁺ from myocardial sarcoplasmic reticulum (SR) in HF leads to excessive Ca²⁺ entering mitochondria, which leads to mitochondrial dysfunction and REDOX imbalance. Excessive accumulation of ROS leads to mitochondrial structure damage, which cannot produce and provide energy. In addition, the accumulation of a large number of ROS can activate NF-κB, leading to myocardial inflammation. Energy deficit in the myocardium has long been considered to be the main mechanism connecting mitochondrial dysfunction and systolic failure. However, exercise can improve the Ca²⁺ imbalance in HF and restore the Ca²⁺ disorder in mitochondria. Similarly, exercise activates mitochondrial dynamics to improve mitochondrial function and reshape intact mitochondrial structure, rebalance mitochondrial REDOX, reduce excessive release of ROS, and rescue cardiomyocyte energy failure in HF. In this review, we summarize recent evidence that exercise can improve Ca²⁺ homeostasis in the SR and activate mitochondrial dynamics, improve mitochondrial function, and reduce oxidative stress levels in HF patients, thereby reducing chronic inflammation in HF patients. The improvement of mitochondrial dynamics is beneficial for ameliorating metabolic flow bottlenecks, REDOX imbalance, ROS balance, impaired mitochondrial Ca²⁺ homeostasis, and inflammation. Interpretation of these findings will lead to new approaches to disease mechanisms and treatment.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2471-2486"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the nexus: pyroptosis and its crucial implications in liver diseases.","authors":"Zeyu Miao, Xiaorong Zhang, Yang Xu, Yan Liu, Qing Yang","doi":"10.1007/s11010-024-05147-1","DOIUrl":"10.1007/s11010-024-05147-1","url":null,"abstract":"<p><p>Pyroptosis, a distinctive form of programmed cell death orchestrated by gasdermin proteins, manifests as cellular rupture, accompanied by the release of inflammatory factors. While pyroptosis is integral to anti-infection immunity, its aberrant activation has been implicated in tumorigenesis. The liver, as the body's largest metabolic organ, is rich in various enzymes and governs metabolism. It is also the primary site for protein synthesis. Recent years have witnessed the emergence of pyroptosis as a significant player in the pathogenesis of specific liver diseases, exerting a pivotal role in both physiological and pathological processes. A comprehensive exploration of pyroptosis can unveil its contributions to the development and regression of conditions such as hepatitis, cirrhosis, and hepatocellular carcinoma, offering innovative perspectives for clinical prevention and treatment. This review consolidates current knowledge on key molecules involved in cellular pyroptosis and delineates their roles in liver diseases. Furthermore, we discuss the potential of leveraging pyroptosis as a novel or existing anti-cancer strategy.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2159-2176"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics research in atherosclerosis.","authors":"Kai-Jiang Tian, Yu Yang, Guo-Shuai Chen, Nian-Hua Deng, Zhen Tian, Rui Bai, Fan Zhang, Zhi-Sheng Jiang","doi":"10.1007/s11010-024-05139-1","DOIUrl":"10.1007/s11010-024-05139-1","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid deposition within the arterial intima, as well as fibrous tissue proliferation and calcification. AS has long been recognized as one of the primary pathological foundations of cardiovascular diseases in humans. Its pathogenesis is intricate and not yet fully elucidated. Studies have shown that AS is associated with oxidative stress, inflammatory response, lipid deposition, and changes in cell phenotype. Unfortunately, there is currently no effective prevention or targeted treatment for AS. The rapid advancement of omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, has opened up novel avenues to elucidate the fundamental pathophysiology and associated mechanisms of AS. Here, we review articles published over the past decade and focus on the current status, challenges, limitations, and prospects of omics in AS research and clinical practice. Emphasizing potential targets based on omics technologies will improve our understanding of this pathological condition and assist in the development of potential therapeutic approaches for AS-related diseases.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2077-2102"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogels in cardiac tissue engineering: application and challenges.","authors":"Yaping Xu, Yuexin Yu, Zhikun Guo","doi":"10.1007/s11010-024-05145-3","DOIUrl":"10.1007/s11010-024-05145-3","url":null,"abstract":"<p><p>Cardiovascular disease remains the leading cause of global mortality. Current stem cell therapy and heart transplant therapy have limited long-term stability in cardiac function. Cardiac tissue engineering may be one of the key methods for regenerating damaged myocardial tissue. As an ideal scaffold material, hydrogel has become a viable tissue engineering therapy for the heart. Hydrogel can not only provide mechanical support for infarcted myocardium but also serve as a carrier for various drugs, bioactive factors, and cells to increase myocardial contractility and improve the cell microenvironment in the infarcted area, thereby improving cardiac function. This paper reviews the applications of hydrogels and biomedical mechanisms in cardiac tissue engineering and discusses the challenge of clinical transformation of hydrogel in cardiac tissue engineering, providing new strategies for treating cardiovascular diseases.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2201-2222"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylene blue reduces monoamine oxidase expression and oxidative stress in human cardiovascular adipose tissue.","authors":"Oana-Maria Aburel, Laurențiu Brăescu, Darius G Buriman, Adrian P Merce, Anca M Bînă, Claudia Borza, Cristian Mornoș, Adrian Sturza, Danina M Muntean","doi":"10.1007/s11010-024-05092-z","DOIUrl":"10.1007/s11010-024-05092-z","url":null,"abstract":"<p><p>Cardiovascular diseases represent the major cause of morbidity mainly due to chronic heart failure. Epicardial (EAT) and perivascular adipose tissues (PVAT) are considered major contributors to the pathogenesis of cardiometabolic pathologies. Monoamine oxidases (MAOs) are mitochondrial enzymes recognized as sources of reactive oxygen species (ROS) in cardiometabolic pathologies. Methylene blue (MB) is one of the oldest protective agents, yet no data are available about its effects on adipose tissue. The present pilot study was aimed at assessing the effects of MB: (i) on MAO expression and (ii) oxidative stress in EAT and PVAT harvested from patients with heart failure subjected to cardiac surgery (n = 25). Adipose tissue samples were incubated with MB (0.1 µM/24 h) and used for the assessment of MAO gene and protein expression (qPCS and immune fluorescence) and ROS production (confocal microscopy and spectrophotometry). The human cardiovascular adipose tissues contain both MAO isoforms, predominantly MAO-A. Incubation with MB reduced MAOs expression and oxidative stress; co-incubation with serotonin, the MAO-A substrate, further augmented ROS generation, an effect partially reversed by MB. In conclusion, MAO-A is the major isoform expressed in EAT and PVAT and contribute to local oxidative stress; both effects can be mitigated by methylene blue.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2413-2421"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causes and consequences of DNA double-stranded breaks in cardiovascular disease.","authors":"A J Marian","doi":"10.1007/s11010-024-05131-9","DOIUrl":"10.1007/s11010-024-05131-9","url":null,"abstract":"<p><p>The genome, whose stability is essential for survival, is incessantly exposed to internal and external stressors, which introduce an estimated 10⁴ to 10⁵ lesions, such as oxidation, in the nuclear genome of each mammalian cell each day. A delicate homeostatic balance between the generation and repair of DNA lesions maintains genomic stability. To initiate transcription, DNA strands unwind to form a transcription bubble and provide a template for the RNA polymerase II (RNAPII) complex to synthesize nascent RNA. The process generates DNA supercoils and introduces torsional stress. To enable RNAPII processing, the supercoils are released by topoisomerases by introducing strand breaks, including double-stranded breaks (DSBs). Thus, DSBs are intrinsic genomic features of gene expression. The breaks are quickly repaired upon processing of the transcription. DNA lesions and damaged proteins involved in transcription could impede the integrity and efficiency of RNAPII processing. The impediment, which is referred to as transcription stress, not only could lead to the generation of aberrant RNA species but also the accumulation of DSBs. The latter is particularly the case when topoisomerase processing and/or the repair mechanisms are compromised. The DSBs activate the DNA damage response (DDR) pathways to repair the damaged DNA and/or impose cell cycle arrest and cell death. In addition, the release of DSBs into the cytosol activates the cytosolic DNA-sensing proteins (CDSPs), which along with the nuclear DDR pathways induce the expression of senescence-associated secretory phenotype (SASP), cell cycle arrest, senescence, cell death, inflammation, and aging. The primary stimulus in hereditary cardiomyopathies is a mutation(s) in genes encoding the protein constituents of cardiac myocytes; however, the phenotype is the consequence of intertwined complex interactions among numerous stressors and the causal mutation(s). Increased internal DNA stressors, such as oxidation, alkylation, and cross-linking, are expected to be common in pathological conditions, including in hereditary cardiomyopathies. In addition, dysregulation of gene expression also imposes transcriptional stress and collectively with other stressors provokes the generation of DSBs. In addition, the depletion of nicotinamide adenine dinucleotide (NAD), which occurs in pathological conditions, impairs the repair mechanism and further facilitates the accumulation of DSBs. Because DSBs activate the DDR pathways, they are expected to contribute to the pathogenesis of cardiomyopathies. Thus, interventions to reduce the generation of DSBs, enhance their repair, and block the deleterious DDR pathways would be expected to impart salubrious effects not only in pathological states, as in hereditary cardiomyopathies but also aging.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2043-2064"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress-induced extracellular vesicles: insight into their altered proteomic composition and probable physiological role in cancer.","authors":"Vaidehi Bhavsar, Ashish Sahu, Ravindra Taware","doi":"10.1007/s11010-024-05121-x","DOIUrl":"10.1007/s11010-024-05121-x","url":null,"abstract":"<p><p>EVs (extracellular vesicles) are phospholipid bilayer vesicles that can be released by both prokaryotic and eukaryotic cells in normal as well as altered physiological conditions. These vesicles also termed as signalosomes, possess a distinctive cargo comprising nucleic acids, proteins, lipids, and metabolites, enabling them to play a pivotal role in both local and long-distance intercellular communication. The composition, origin, and release of EVs can be influenced by different physiological conditions and a variety of stress factors, consequently affecting the contents carried within these vesicles. Therefore, identifying the modified contents of EVs can provide valuable insights into their functional role in stress-triggered communication. Particularly, this is important when EVs released from tumor microenvironment are investigated for their role in the development and dissemination of cancer. This review article emphasizes the importance of differential EV shedding and altered proteomic content in response to reduced oxygen concentration, altered levels of glucose and glutamine, pH variations, oxidative stress and Ca²⁺ ion concertation and it is subsequent effects on the behavior of recipient cells.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"2025-2041"},"PeriodicalIF":3.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}