Molecular biomedicine最新文献_第7页

Y-27632 targeting ROCK1&2 modulates cell growth, fibrosis and epithelial-mesenchymal transition in hyperplastic prostate by inhibiting β-catenin pathway. 靶向ROCK1&2的Y-27632通过抑制β-catenin通路调节增生性前列腺的细胞生长、纤维化和上皮-间质转化。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-26 DOI: 10.1186/s43556-024-00216-9

Shidong Shan, Min Su, Hejin Wang, Feng Guo, Yan Li, Yongying Zhou, Huan Liu, Lu Du, Junchao Zhang, Jizhang Qiu, Michael E DiSanto, Yuming Guo, Xinhua Zhang

{"title":"Y-27632 targeting ROCK1&2 modulates cell growth, fibrosis and epithelial-mesenchymal transition in hyperplastic prostate by inhibiting β-catenin pathway.","authors":"Shidong Shan, Min Su, Hejin Wang, Feng Guo, Yan Li, Yongying Zhou, Huan Liu, Lu Du, Junchao Zhang, Jizhang Qiu, Michael E DiSanto, Yuming Guo, Xinhua Zhang","doi":"10.1186/s43556-024-00216-9","DOIUrl":"10.1186/s43556-024-00216-9","url":null,"abstract":"Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad2/3 signaling. At the in vivo level, Y-27632 reversed prostatic hyperplasia and fibrosis in BPH model rats to some extent. Our study sheds light on the therapeutic potential of Y-27632 in regulating prostate cell growth, fibrosis and EMT, and demonstrates for the first time the regulatory effect of ROCK isoforms on prostate cells, providing the basis for future research of ROCK isoform-selective inhibitors.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"52"},"PeriodicalIF":6.3,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of nitric oxide-mediated necroptosis as the predominant death route in Parkinson's disease. 确定一氧化氮介导的坏死是帕金森病的主要死亡途径。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-24 DOI: 10.1186/s43556-024-00213-y

Ting Zhang, Wenjing Rui, Yue Sun, Yunyun Tian, Qiaoyan Li, Qian Zhang, Yanchun Zhao, Zongzhi Liu, Tiepeng Wang

{"title":"Identification of nitric oxide-mediated necroptosis as the predominant death route in Parkinson's disease.","authors":"Ting Zhang, Wenjing Rui, Yue Sun, Yunyun Tian, Qiaoyan Li, Qian Zhang, Yanchun Zhao, Zongzhi Liu, Tiepeng Wang","doi":"10.1186/s43556-024-00213-y","DOIUrl":"10.1186/s43556-024-00213-y","url":null,"abstract":"Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in disease progression remains unclear. This study employed RNA sequencing (RNA-seq) of brain tissue to explore gene expression patterns across different stages of PD. Using the Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic cell death pathways to identify the predominant routes of neuronal death during PD progression. Our cell type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) expression across most neuronal subtypes. In vitro experiments confirmed that nitric oxide (NO) is a key mediator of necroptosis, leading to nuclear shrinkage and decreased mitochondrial membrane potential via phosphorylation of the PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated neuronal damage in both in vitro and in vivo PD models. Further analysis revealed that NO-mediated necroptosis is prevalent in early-onset Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) and across multiple brain regions but not in brain tumours. Our findings suggest that NO-mediated necroptosis is a critical pathway in PD and other neurodegenerative disorders, providing potential targets for therapeutic intervention.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"44"},"PeriodicalIF":6.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deleting fibroblast growth factor 2 in macrophages aggravates septic acute lung injury by increasing M1 polarization and inflammatory cytokine secretion. 删除巨噬细胞中的成纤维细胞生长因子 2 会增加 M1 极化和炎性细胞因子分泌，从而加重脓毒症急性肺损伤。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-22 DOI: 10.1186/s43556-024-00203-0

Lingxian Yi, Yu Chen, Yaoyang Zhang, Haiquan Huang, Jiahui Li, Yirui Qu, Tujun Weng, Jiake Chai

{"title":"Deleting fibroblast growth factor 2 in macrophages aggravates septic acute lung injury by increasing M1 polarization and inflammatory cytokine secretion.","authors":"Lingxian Yi, Yu Chen, Yaoyang Zhang, Haiquan Huang, Jiahui Li, Yirui Qu, Tujun Weng, Jiake Chai","doi":"10.1186/s43556-024-00203-0","DOIUrl":"10.1186/s43556-024-00203-0","url":null,"abstract":"Septic lung injury is strongly associated with polarization of M1 macrophages and excessive cytokine release. Fibroblast growth factor (FGF) signaling plays a role in both processes. However, the impact of FGF2 deficiency on macrophage polarization and septic acute lung injury remains unclear. To investigate this, we obtained macrophages from FGF2 knockout mice and examined their polarization and inflammatory cytokine expression. We also eliminated endogenous macrophages using clodronate liposomes and administered FGF2 knockout or WT macrophages intravenously in conjunction with cecal ligation and puncture (CLP) surgery to induce sepsis. In vitro analysis by flow cytometry and real-time PCR analysis demonstrated that FGF2 deficiency resulted in increased expression of M1 markers (iNOS and CD86) and inflammatory cytokines (CXCL1, IL1β, and IL6), especially after LPS stimulation. Additionally, immunofluorescence demonstrated increased nuclear translocation of p65 NF-κB in FGF2 knockout macrophages and RNA-seq analysis showed enrichment of differentially expressed genes in the IL17 and TNFα inflammatory signaling pathways. Furthermore, in vivo experiments revealed that depletion of FGF2 in macrophages worsened sepsis-induced lung inflammation, lung vascular leak, and lung histological injury, accompanied by an increase in CD86-positive cells and apoptosis. Our study suggests that FGF2 deficiency in macrophages plays a critical role in the pathogenesis of septic ALI, possibly because of the enhanced M1 macrophage polarization and production of proinflammatory cytokines. These findings provide empirical evidence for potential therapeutic interventions targeting FGF2 signaling to modulate the polarization of M1 and M2 macrophages in the management of sepsis-induced acute lung injury.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"50"},"PeriodicalIF":6.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultraviolet (UV) radiation: a double-edged sword in cancer development and therapy. 紫外线（UV）辐射：癌症发展和治疗的双刃剑。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-17 DOI: 10.1186/s43556-024-00209-8

Zhen-Wei Yu, Min Zheng, Hua-Yang Fan, Xin-Hua Liang, Ya-Ling Tang

{"title":"Ultraviolet (UV) radiation: a double-edged sword in cancer development and therapy.","authors":"Zhen-Wei Yu, Min Zheng, Hua-Yang Fan, Xin-Hua Liang, Ya-Ling Tang","doi":"10.1186/s43556-024-00209-8","DOIUrl":"https://doi.org/10.1186/s43556-024-00209-8","url":null,"abstract":"It has long been widely acknowledged that ultraviolet (UV) light is an environment risk factor that can lead to cancer, particularly skin cancer. However, it is worth noting that UV radiation holds potential for cancer treatment as a relatively high-energy electromagnetic wave. With the help of nanomaterials, the role of UV radiation has caught increasing attention in cancer treatment. In this review, we briefly summarized types of UV-induced cancers, including malignant melanoma, squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma. Importantly, we discussed the primary mechanisms underlying UV carcinogenesis, including mutations by DNA damage, immunosuppression, inflammation and epigenetic alterations. Historically limited by its shallow penetration depth, the introduction of nanomaterials has dramatically transformed the utilization of UV light in cancer treatment. The direct effect of UV light itself generally leads to the suppression of cancer cell growth and the initiation of apoptosis and ferroptosis. It can also be utilized to activate photosensitizers for reactive oxygen species (ROS) production, sensitize radiotherapy and achieve controlled drug release. Finally, we comprehensively weigh the significant risks and limitations associated with the therapeutic use of UV radiation. And the contradictory effect of UV exposure in promoting and inhibiting tumor has been discussed. This review provides clues for potential clinical therapy as well as future study directions in the UV radiation field. The precise delivery and control of UV light or nanomaterials and the wavelength as well as dose effects of UV light are needed for a thorough understanding of UV radiation.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"49"},"PeriodicalIF":6.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Treatment-resistant depression: molecular mechanisms and management. 耐药性抑郁症：分子机制与管理。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-17 DOI: 10.1186/s43556-024-00205-y

Mayanja M Kajumba, Angelina Kakooza-Mwesige, Noeline Nakasujja, Deborah Koltai, Turhan Canli

{"title":"Treatment-resistant depression: molecular mechanisms and management.","authors":"Mayanja M Kajumba, Angelina Kakooza-Mwesige, Noeline Nakasujja, Deborah Koltai, Turhan Canli","doi":"10.1186/s43556-024-00205-y","DOIUrl":"10.1186/s43556-024-00205-y","url":null,"abstract":"Due to the heterogeneous nature of depression, the underlying etiological mechanisms greatly differ among individuals, and there are no known subtype-specific biomarkers to serve as precise targets for therapeutic efficacy. The extensive research efforts over the past decades have not yielded much success, and the currently used first-line conventional antidepressants are still ineffective for close to 66% of patients. Most clinicians use trial-and-error treatment approaches, which seem beneficial to only a fraction of patients, with some eventually developing treatment resistance. Here, we review evidence from both preclinical and clinical studies on the pathogenesis of depression and antidepressant treatment response. We also discuss the efficacy of the currently used pharmacological and non-pharmacological approaches, as well as the novel emerging therapies. The review reveals that the underlying mechanisms in the pathogenesis of depression and antidepressant response, are not specific, but rather involve an interplay between various neurotransmitter systems, inflammatory mediators, stress, HPA axis dysregulation, genetics, and other psycho-neurophysiological factors. None of the current depression hypotheses sufficiently accounts for the interactional mechanisms involved in both its etiology and treatment response, which could partly explain the limited success in discovering efficacious antidepressant treatment. Effective management of treatment-resistant depression (TRD) requires targeting several interactional mechanisms, using subtype-specific and/or personalized therapeutic modalities, which could, for example, include multi-target pharmacotherapies in augmentation with psychotherapy and/or other non-pharmacological approaches. Future research guided by interaction mechanisms hypotheses could provide more insights into potential etiologies of TRD, precision biomarker targets, and efficacious therapeutic modalities.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"43"},"PeriodicalIF":6.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monoclonal antibodies: From magic bullet to precision weapon. 单克隆抗体：从神奇子弹到精确武器

IF 6.3

Molecular biomedicine Pub Date : 2024-10-11 DOI: 10.1186/s43556-024-00210-1

Hassan Aboul-Ella, Asmaa Gohar, Aya Ahmed Ali, Lina M Ismail, Adham Ezz El-Regal Mahmoud, Walid F Elkhatib, Heba Aboul-Ella

{"title":"Monoclonal antibodies: From magic bullet to precision weapon.","authors":"Hassan Aboul-Ella, Asmaa Gohar, Aya Ahmed Ali, Lina M Ismail, Adham Ezz El-Regal Mahmoud, Walid F Elkhatib, Heba Aboul-Ella","doi":"10.1186/s43556-024-00210-1","DOIUrl":"10.1186/s43556-024-00210-1","url":null,"abstract":"Monoclonal antibodies (mAbs) are used to prevent, detect, and treat a broad spectrum of non-communicable and communicable diseases. Over the past few years, the market for mAbs has grown exponentially with an expected compound annual growth rate (CAGR) of 11.07% from 2024 (237.64 billion USD estimated at the end of 2023) to 2033 (679.03 billion USD expected by the end of 2033). Ever since the advent of hybridoma technology introduced in 1975, antibody-based therapeutics were realized using murine antibodies which further progressed into humanized and fully human antibodies, reducing the risk of immunogenicity. Some benefits of using mAbs over conventional drugs include a drastic reduction in the chances of adverse reactions, interactions between drugs, and targeting specific proteins. While antibodies are very efficient, their higher production costs impede the process of commercialization. However, their cost factor has been improved by developing biosimilar antibodies as affordable versions of therapeutic antibodies. Along with the recent advancements and innovations in antibody engineering have helped and will furtherly help to design bio-better antibodies with improved efficacy than the conventional ones. These novel mAb-based therapeutics are set to revolutionize existing drug therapies targeting a wide spectrum of diseases, thereby meeting several unmet medical needs. This review provides comprehensive insights into the current fundamental landscape of mAbs development and applications and the key factors influencing the future projections, advancement, and incorporation of such promising immunotherapeutic candidates as a confrontation approach against a wide list of diseases, with a rationalistic mentioning of any limitations facing this field.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"47"},"PeriodicalIF":6.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ulcerative colitis: molecular insights and intervention therapy. 溃疡性结肠炎：分子研究与干预治疗。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-10 DOI: 10.1186/s43556-024-00207-w

Yuqing Liang, Yang Li, Chehao Lee, Ziwei Yu, Chongli Chen, Chao Liang

{"title":"Ulcerative colitis: molecular insights and intervention therapy.","authors":"Yuqing Liang, Yang Li, Chehao Lee, Ziwei Yu, Chongli Chen, Chao Liang","doi":"10.1186/s43556-024-00207-w","DOIUrl":"10.1186/s43556-024-00207-w","url":null,"abstract":"Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, diarrhea, rectal bleeding, and weight loss. The pathogenesis and treatment of UC remain key areas of research interest. Various factors, including genetic predisposition, immune dysregulation, and alterations in the gut microbiota, are believed to contribute to the pathogenesis of UC. Current treatments for UC include 5-aminosalicylic acids, corticosteroids, immunosuppressants, and biologics. However, study reported that the one-year clinical remission rate is only around 40%. It is necessary to prompt the exploration of new treatment modalities. Biologic therapies, such as anti-TNF-α monoclonal antibody and JAK inhibitor, primarily consist of small molecules targeting specific pathways, effectively inducing and maintaining remission. Given the significant role of the gut microbiota, research into intestinal microecologics, such as probiotics and prebiotics, and fecal microbiota transplantation (FMT) shows promising potential in UC treatment. Additionally, medicinal herbs, such as chili pepper and turmeric, used in complementary therapy have shown promising results in UC management. This article reviews recent findings on the mechanisms of UC, including genetic susceptibility, immune cell dynamics and cytokine regulation, and gut microbiota alterations. It also discusses current applications of biologic therapy, herbal therapy, microecologics, and FMT, along with their prospects and challenges.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"42"},"PeriodicalIF":6.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathways regulating intestinal stem cells and potential therapeutic targets for radiation enteropathy. 调节肠干细胞的途径和辐射性肠病的潜在治疗靶点

IF 6.3

Molecular biomedicine Pub Date : 2024-10-10 DOI: 10.1186/s43556-024-00211-0

Si-Min Chen, Bing-Jie Guo, An-Qiang Feng, Xue-Lian Wang, Sai-Long Zhang, Chao-Yu Miao

{"title":"Pathways regulating intestinal stem cells and potential therapeutic targets for radiation enteropathy.","authors":"Si-Min Chen, Bing-Jie Guo, An-Qiang Feng, Xue-Lian Wang, Sai-Long Zhang, Chao-Yu Miao","doi":"10.1186/s43556-024-00211-0","DOIUrl":"10.1186/s43556-024-00211-0","url":null,"abstract":"Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, the procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks of radiation-induced enteropathy upon reaching threshold doses. Stem cells within the intestinal crypts, through their controlled proliferation and differentiation, support the critical functions of the intestinal epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem cells (ISCs) regulation is intricately orchestrated by diverse signaling pathways, among which are the WNT, BMP, NOTCH, EGF, Hippo, Hedgehog and NF-κB, each contributing to the complex control of these cells' behavior. Complementing these pathways are additional regulators such as nutrient metabolic states, and the intestinal microbiota, all of which contribute to the fine-tuning of ISCs behavior in the intestinal crypts. It is the harmonious interplay among these signaling cascades and modulating elements that preserves the homeostasis of intestinal epithelial cells (IECs), thereby ensuring the gut's overall health and function. This review delves into the molecular underpinnings of how stem cells respond in the context of radiation enteropathy, aiming to illuminate potential biological targets for therapeutic intervention. Furthermore, we have compiled a summary of several current treatment methodologies. By unraveling these mechanisms and treatment methods, we aspire to furnish a roadmap for the development of novel therapeutics, advancing our capabilities in mitigating radiation-induced intestinal damage.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"46"},"PeriodicalIF":6.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HJURP sustains ferroptosis sensitivity of TNBC by interacting with SLC7A11 and maintaining its function. HJURP 通过与 SLC7A11 相互作用并维持其功能，维持 TNBC 的铁蛋白沉积敏感性。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-03 DOI: 10.1186/s43556-024-00208-9

Yongxia Chen, Kaili Cen, Linbo Wang, Jian Ruan, Yunlu Jia

引用次数: 0

Repurposing metabolic regulators: antidiabetic drugs as anticancer agents. 代谢调节剂的再利用：作为抗癌药物的抗糖尿病药物。

IF 6.3

Molecular biomedicine Pub Date : 2024-09-28 DOI: 10.1186/s43556-024-00204-z

Yogita Dhas, Nupur Biswas, Divyalakshmi M R, Lawrence D Jones, Shashaanka Ashili

{"title":"Repurposing metabolic regulators: antidiabetic drugs as anticancer agents.","authors":"Yogita Dhas, Nupur Biswas, Divyalakshmi M R, Lawrence D Jones, Shashaanka Ashili","doi":"10.1186/s43556-024-00204-z","DOIUrl":"https://doi.org/10.1186/s43556-024-00204-z","url":null,"abstract":"Drug repurposing in cancer taps into the capabilities of existing drugs, initially designed for other ailments, as potential cancer treatments. It offers several advantages over traditional drug discovery, including reduced costs, reduced development timelines, and a lower risk of adverse effects. However, not all drug classes align seamlessly with a patient's condition or long-term usage. Hence, repurposing of chronically used drugs presents a more attractive option. On the other hand, metabolic reprogramming being an important hallmark of cancer paves the metabolic regulators as possible cancer therapeutics. This review emphasizes the importance and offers current insights into the repurposing of antidiabetic drugs, including metformin, sulfonylureas, sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), thiazolidinediones (TZD), and α-glucosidase inhibitors, against various types of cancers. Antidiabetic drugs, regulating metabolic pathways have gained considerable attention in cancer research. The literature reveals a complex relationship between antidiabetic drugs and cancer risk. Among the antidiabetic drugs, metformin may possess anti-cancer properties, potentially reducing cancer cell proliferation, inducing apoptosis, and enhancing cancer cell sensitivity to chemotherapy. However, other antidiabetic drugs have revealed heterogeneous responses. Sulfonylureas and TZDs have not demonstrated consistent anti-cancer activity, while SGLT2 inhibitors and DPP-4 inhibitors have shown some potential benefits. GLP-1RAs have raised concerns due to possible associations with an increased risk of certain cancers. This review highlights that further research is warranted to elucidate the mechanisms underlying the potential anti-cancer effects of these drugs and to establish their efficacy and safety in clinical settings.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"40"},"PeriodicalIF":6.3,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0