Molecular biomedicine最新文献_第4页

T cell receptor repertoire characteristics and therapeutic potential of tumor infiltrating lymphocytes (TILs) derived from metastatic lymph node in cervical cancer. 来自宫颈癌转移淋巴结的肿瘤浸润淋巴细胞（TILs）的T细胞受体谱系特征和治疗潜力。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-04 DOI: 10.1186/s43556-024-00215-w

Xuan Zhao, Zhenjiang Liu, Haifeng Qin, Yarong Liu, Yi Zhang

引用次数: 0

Decorin-armed oncolytic adenovirus promotes natural killers (NKs) activation and infiltration to enhance NK therapy in CRC model. 带装饰素的溶瘤腺病毒可促进自然杀伤因子（NKs）的激活和浸润，从而增强对 CRC 模型的 NK 治疗。

IF 6.3

Molecular biomedicine Pub Date : 2024-11-01 DOI: 10.1186/s43556-024-00212-z

Xue Li, Yuning Zhang, Zhuang Mao, Huiqiang Zhao, Hu Cao, Jingyi Wang, Wei Liu, Shiyun Dai, Yuefeng Yang, Yuanyuan Huang, Hua Wang

{"title":"Decorin-armed oncolytic adenovirus promotes natural killers (NKs) activation and infiltration to enhance NK therapy in CRC model.","authors":"Xue Li, Yuning Zhang, Zhuang Mao, Huiqiang Zhao, Hu Cao, Jingyi Wang, Wei Liu, Shiyun Dai, Yuefeng Yang, Yuanyuan Huang, Hua Wang","doi":"10.1186/s43556-024-00212-z","DOIUrl":"10.1186/s43556-024-00212-z","url":null,"abstract":"Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"48"},"PeriodicalIF":6.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560345","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

Post-translational modifications of fibrinogen: implications for clotting, fibrin structure and degradation. 纤维蛋白原的翻译后修饰：对凝血、纤维蛋白结构和降解的影响。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-31 DOI: 10.1186/s43556-024-00214-x

Francesca Nencini, Alessandra Bettiol, Flavia Rita Argento, Serena Borghi, Elvira Giurranna, Giacomo Emmi, Domenico Prisco, Niccolò Taddei, Claudia Fiorillo, Matteo Becatti

{"title":"Post-translational modifications of fibrinogen: implications for clotting, fibrin structure and degradation.","authors":"Francesca Nencini, Alessandra Bettiol, Flavia Rita Argento, Serena Borghi, Elvira Giurranna, Giacomo Emmi, Domenico Prisco, Niccolò Taddei, Claudia Fiorillo, Matteo Becatti","doi":"10.1186/s43556-024-00214-x","DOIUrl":"10.1186/s43556-024-00214-x","url":null,"abstract":"Fibrinogen, a blood plasma protein with a key role in hemostasis and thrombosis, is highly susceptible to post-translational modifications (PTMs), that significantly influence clot formation, structure, and stability. These PTMs, which include acetylation, amidation, carbamylation, citrullination, dichlorination, glycation, glycosylation, guanidinylation, hydroxylation, homocysteinylation, malonylation, methylation, nitration, oxidation, phosphorylation and sulphation, can alter fibrinogen biochemical properties and affect its functional behavior in coagulation and fibrinolysis. Oxidation and nitration are notably associated with oxidative stress, impacting fibrin fiber formation and promoting the development of more compact and resistant fibrin networks. Glycosylation and glycation contribute to altered fibrinogen structural properties, often resulting in changes in fibrin clot density and susceptibility to lysis, particularly in metabolic disorders like diabetes. Acetylation and phosphorylation, influenced by medications such as aspirin, modulate clot architecture by affecting fiber thickness and clot permeability. Citrullination and homocysteinylation, although less studied, are linked to autoimmune conditions and cardiovascular diseases, respectively, affecting fibrin formation and stability. Understanding these modifications provides insights into the pathophysiology of thrombotic disorders and highlights potential therapeutic targets. This review comprehensively examines the current literature on fibrinogen PTMs, their specific sites, biochemical pathways, and their consequences on fibrin clot architecture, clot formation and clot lysis.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"45"},"PeriodicalIF":6.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549395","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

Systemic lupus erythematosus: pathogenesis and targeted therapy. 系统性红斑狼疮：发病机制和靶向治疗。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-30 DOI: 10.1186/s43556-024-00217-8

Xu Su, Hui Yu, Qingqiang Lei, Xuerui Chen, Yanli Tong, Zhongyang Zhang, Wenyong Yang, Yuanbiao Guo, Liangbin Lin

{"title":"Systemic lupus erythematosus: pathogenesis and targeted therapy.","authors":"Xu Su, Hui Yu, Qingqiang Lei, Xuerui Chen, Yanli Tong, Zhongyang Zhang, Wenyong Yang, Yuanbiao Guo, Liangbin Lin","doi":"10.1186/s43556-024-00217-8","DOIUrl":"10.1186/s43556-024-00217-8","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress and status of traditional and emerging treatment strategies for SLE. Traditional treatment strategies for SLE have mainly employed non-specific approaches, including cytotoxic and immunosuppressive drugs, antimalarials, glucocorticoids, and NSAIDs. These strategies are effective in mitigating the effects of the disease, but they are not a complete cure and are often accompanied by adverse reactions. Emerging targeted therapeutic drugs, on the other hand, aim to control and treat SLE by targeting B and T cells, inhibiting their activation and function, as well as the abnormal activation of the immune system. A deeper understanding of the pathogenesis of SLE and the exploration of new targeted treatment strategies are essential to advance the treatment of this complex autoimmune disease.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"54"},"PeriodicalIF":6.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549396","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

The functions of apolipoproteins and lipoproteins in health and disease. 脂蛋白和脂蛋白在健康和疾病中的功能。

IF 6.3

Molecular biomedicine Pub Date : 2024-10-28 DOI: 10.1186/s43556-024-00218-7

Zijun Ma, Jixin Zhong, Wei Tu, Shiliang Li, Jun Chen

{"title":"The functions of apolipoproteins and lipoproteins in health and disease.","authors":"Zijun Ma, Jixin Zhong, Wei Tu, Shiliang Li, Jun Chen","doi":"10.1186/s43556-024-00218-7","DOIUrl":"10.1186/s43556-024-00218-7","url":null,"abstract":"Lipoproteins and apolipoproteins are crucial in lipid metabolism, functioning as essential mediators in the transport of cholesterol and triglycerides and being closely related to the pathogenesis of multiple systems, including cardiovascular. Lipoproteins a (Lp(a)), as a unique subclass of lipoproteins, is a low-density lipoprotein(LDL)-like particle with pro-atherosclerotic and pro-inflammatory properties, displaying high heritability. More and more strong evidence points to a possible link between high amounts of Lp(a) and cardiac conditions like atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis (AS), making it a risk factor for heart diseases. In recent years, Lp(a)'s role in other diseases, including neurological disorders and cancer, has been increasingly recognized. Although therapies aimed at low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have achieved significant success, elevated Lp(a) levels remain a significant clinical management problem. Despite the limited efficacy of current lipid-lowering therapies, major clinical advances in new Lp(a)-lowering therapies have significantly advanced the field. This review, grounded in the pathophysiology of lipoproteins, seeks to summarize the wide-ranging connections between lipoproteins (such as LDL-C and HDL-C) and various diseases, alongside the latest clinical developments, special emphasis is placed on the pivotal role of Lp(a) in cardiovascular disease, while also examining its future potential and mechanisms in other conditions. Furthermore, this review discusses Lp(a)-lowering therapies and highlights significant recent advances in emerging treatments, advocates for further exploration into Lp(a)'s pathogenic mechanisms and its potential as a therapeutic target, proposing new secondary prevention strategies for high-risk individuals.","PeriodicalId":74218,"journal":{"name":"Molecular biomedicine","volume":"5 1","pages":"53"},"PeriodicalIF":6.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514173","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

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