Clinical and translational discovery最新文献

Tumour microenvironment (TME) is one of the important factors associated with cancer progression. TME is a multicellular system composed of fibroblasts, endothelial and immune cells, distributed in the extracellular matrix (ECM), and closely interacts with tumour cells to promote the occurrence and development of cancers. In TME, secreted products of various immune and non-immune cell types, such as cytokines and chemokines, as well as metabolites, hypoxia, angiogenesis and ECM remodelling drive chronic inflammation.¹ Recent studies have shown that cancer-associated fibroblasts (CAFs) are important regulators of anti-tumour immune response. CAFs can reshape TME by secreting a variety of cytokines, thereby promoting immune escape. Therefore, targeting CAFs may improve the effectiveness of immunotherapy.^{2, 3} For example, NOX4 inhibitors can reverse the formation of CAFs, thereby restoring anti-tumor immunotherapy efficacy.³ However, due to the high heterogeneity of the CAF population, its origin and function remain unclear, and the lack of understanding of these issues greatly limits the clinical transformation of CAFs.⁴

The development of single-cell transcriptome sequencing (scRNA-seq) has brought fundamental advances in cancer research. The subpopulations and functions of CAFs in non-small-cell lung cancer (NSCLC) have been described in several studies using scRNA-seq.^5-7 However, due to the loss of spatial information, most studies limited their research focus to immune cells in tumours. The emergence of spatial omics technology has made up for the shortcomings of single-cell sequencing, using spatial transcriptome technologies, it is expected to characterize the molecular characteristics and immune regulatory functions of CAFs in cancer.

In a recent study by Xu et al., a subpopulation of CAFs, POSTN⁺ CAFs were found to have a close localization with SPP1⁺ macrophages, and correlated with exhausted phenotypes and lower infiltration of T cells in NSCLC.⁸ Initially, the study identified diverse fibroblast subpopulations in NSCLC through the integration of fibroblasts in the Peking cohort (N = 1986) with fibroblasts in Samsung cohort⁶ (N = 3499) and Tongji cohort⁷ (N = 4497). Several iCAF subpopulations (clusters C01_CCL11, C05_IGF1 and C06_CCL2), adventitial fibroblasts (C03_PI16), alveolar fibroblasts (C04_COL13A1), as well as myCAF subgroups (C02_POSTN, C07_MKI67 and C09_MYH11) were identified. Specifically, they found that POSTN⁺ CAFs (C02_POSTN) were enriched in tumour/metastatic samples compared to normal samples. Gene Set Variation Analysis was performed and POSTN⁺ CAFs showed activities in several pro-invasive pathways such as “angiogenesis” and

Telocytes (TCs) are a new type of interstitial cell identified in multiple tissues of mammals, including the human lung, and mediate homocellular or heterocellular cell-cell communication. Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure and combined with direct and indirect lung injury, which is induced by pneumonia, sepsis, burns, etc. Pulmonary fibrosis is a progressive lung disease that occurs due to increased fibrosis of lung tissue in response to chronic injury of the epithelium and gets more and more attention as a well-recognized sequela of ARDS or mechanical ventilation. However, the existing intervention measures could not prevent the progression of pulmonary fibrosis. Although the protective effect of TCs in acute lung injury had been demonstrated in both cellular and animal models in previous studies by our or other researchers, the roles of TCs mediated cell-cell communication in fibroproliferative ARDS is unclear. This review is aimed at integrating our understanding of TC-mediated cell–cell communication in lung diseases with pulmonary fibrosis after ARDS.

Cancer is an unsolved health crisis that affects a large number of world's population.¹ Breast cancer is the most challenging problem in the current time and this cancer affects a huge female population every year.² Several factors are involved in breast cancer such as age, genetic mutation, obesity, food habits, family history, etc. In this situation, we need an affordable, effective, and efficient theranostics approach. This global crisis is addressed via nanomedicine, which is an applied domain of nanotechnology (it is related to cancer diagnosis, sensor, and therapeutics development based on nanomaterials and nanotechnology).³ Nanoparticles based nanomedicine has dynamic application in cancer diagnostic tools development,  therapeutic approach development, and several biological molecules transports.⁴ It is also an effective and specific drug transport vehicle for breast cancer.⁴ The purpose of nanomedicine is to develop a strong immune response (cellular and humoral immune response together) against cancer. Nanovaccine (majorly based on nanoparticle modification for cellular transport) is more stable, biocompatible, and less toxic.^{5, 6} Immune response developmentary antigen protein-loaded particles are developed Treg (regulatory T-cells) cells mediated immune response.⁷ Nanomedicine becomes a promising solution for breast cancer. Nanomaterial size, surface charges, and chemical composition play principleroles in therapeutic release, cytotoxicity, and drug-uptake phenomena.⁸ The scientific investigation currently highlights that during cancer development and progression, extracellular vesicles (EVs) play a regulatory role in cancer.⁹ This type of invention introduces a new member of nanomedicine, called EVs. In breast cancer, exosomes (a subpopulation of EVs) regulate several stages of cancer development (cancer cell proliferation, angiogenesis, immune cells suppression, metastasis, and drug and therapeutic-resistance development).^10-13 Exosomes cargo molecules are significantly influenced by breast cancer development.¹⁰ Blood-circulated exosomes carry signature breast cancer biomarkers (diagnostic and prognostic biomarkers).^{10, 13} In breast cancer, the most challenging part of early diagnosis. Exosomes-based liquid biopsy is the most efficient approach for screening cancer compared to tissue biopsy.¹⁴ The current development of nanomedicine indicates that single exosome profiling, exosome barcoding, exosome sensor, and multi-omic approaches are leading frontier combating for breast cancer.^{15, 16} Plant-source exosomes (tea leaf exosomes) based nanomedicine also (tea leaf exosomes) show breast cancer healing ac

Numerous studies have demonstrated socioeconomic differences in cancer incidence and outcomes, including shorter cancer survival times in patients with lower educational attainment and income, which represent important indicators of lower socioeconomic status (SES). The hypothesis proposing that disparities in cancer outcomes and mortality linked to the social determinants of health (SDoH) can be accounted for by higher risk factor prevalences or the interrelation of various SDoH has been contradicted by current evidence and previous studies have introduced potential biological mechanisms of the SDoH which are summarised by the term ‘biology of socioeconomic adversity’. Socioeconomic inequalities in cancer risk and outcomes cannot be entirely attributed to differences in clinical, behavioural, and environmental risk factors in current clinical research. Hence, it is crucial to investigate various factors, including specific biomarkers and pathophysiological pathways affected by the SDoH.

For more than 30 years, numerous studies have demonstrated socioeconomic differences in cancer incidence and survival.^1-3 In the first place, it was found that shorter survival times in solid cancers and lymphoma are associated with lower income and education levels, two important indicators of lower SES, and it was noted that this effect could not be accounted for by the stage of disease at initial presentation and that this association persisted after statistically adjusting for all known prognostic factors.⁴ Today, socioeconomic inequalities in cancer survival rates still persist in clinical trials despite access to protocol-directed care,⁵ implying that optimal equitable healthcare cannot resolve inequalities in outcomes. For these reasons, a multiplex approach to this global health problem is necessary.

The hypothesis proposing that disparities in premature and cancer mortality linked to the SDoH can be accounted for by higher risk factor prevalences, like smoking, as well as by the interrelation of various SDoH, such as low income and living in adverse neighbourhood physical and social environments which aggregate within an individual, thereby amplifying health effects, holds significant appeal. However, it has been estimated that only about half of the association between area-level SES, which includes factors such as income, education, and occupation at the neighbourhood level, and cancer mortality risk can be explained by higher rates of individual-level risk factors including smoking, diet, physical activity, participation in cancer screening programs, and obesity.⁶ Even more, current evidence contradicts the idea that differences in cancer-associated mortality based on educational attainment, an often used indicator of individual-level SES and a key SDoH, can be attributed to differences in conventional cancer risk factors or the interrelation

Moyamoya disease (MMD) is a rare cerebrovascular condition characterized by a chronic and progressive narrowing of the terminal portion of the bilateral internal carotid arteries, causing the formation of an abnormal vascular network. These compensatory brain vessels often prove insufficient, leading MMD patients to severe ischemic or hemorrhagic clinical manifestations. Surgical treatment, mainly based on direct and indirect revascularization, represents the preferred procedure for MMD patients until now, for improving cerebral hemodynamics and decreasing the pathological collateral network development. The specific mechanism underlying both the progressive arterial wall thickening and the spontaneous angiogenesis of the defective moyamoya vessels remains poorly understood. Moreover, the lack of reliable animal or cellular pre-clinical models and the heterogeneous data on MMD pathophysiology have hampered the clinical validation of powerful biomarkers, as well as the development of tailored therapeutic options.

The previous investigations aimed at biomarker discovery mainly addressed patients’ peripheral blood samples, which may not reflect the real pathological changes of MMD cerebral vessels. On the other hand, prior interesting studies involving cerebral artery specimens (e.g. middle cerebral artery [MCA]) were performed through RNA microarray techniques, which have several limitations as compared to high-throughput RNA sequencing (RNA-seq). As an example, the long noncoding RNA profile of MMD patients’ MCA provided data regarding antibacterial response, T-cell receptor signalling pathway and cytokine production.¹ Interestingly, Xu et al. carried out an RNA-seq analysis of MMD patients’ MCA, as compared to atherosclerosis-associated intracranial artery stenosis/occlusion. The authors identified several differential expressed genes mainly involved in extracellular matrix organization and mitochondrial function, thus highlighting novel insights into disease pathogenesis.²

Since the challenging sampling of cerebral artery specimens for transcriptomic studies, other ultrasensitive techniques were recently carried out for molecular profiling of circulating biomarkers from cerebrospinal fluid (CSF) or blood. The study by Ota et al. through a next-generation sequencing (NGS) approach demonstrated that specific changes occurred in the expression levels of extracellular vesicle-derived microRNAs (miRNAs), extracted from intracranial CSF of MMD patients when compared to controls.³ The authors suggested that MMD has a specific regulatory mechanism for angiogenesis, different from that found in other ischemic disorders. Proteomic approaches towards MMD patients’ circulating fluids have already been reported. Tandem mass tag (TMT)-labelled proteome analysis was performed on serum-derived exosomes, extracted from pure ischemic or hemorrhagic MMD patients and healthy cont

Revolutionizing cancer care, chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy anticancer treatment that uses genetically modified T-cells to combat cancer. Nurses have a key role in fostering resilience in patients and caregivers undergoing this therapy, and in navigating ethical and legal issues and safeguarding their rights and interests. Unlike haematological malignancies, solid tumours have more diverse and heterogeneous tumour-associated antigens (TAAs), which can lead to off-target toxicity or antigen escape.¹

Resilience enables the adversity to rebound from stress and trauma even amid faced with uncertainties risks and side effects including cytokine release syndrome, hypogammaglobulinemia, neurotoxicity, infection, prolonged cytopenias, and organ damage, and can lead to life-threatening in some cases (See Figure 1).

Mr. Bende contributed to preparing and collecting original literature and figures and writing and editing the manuscript.

The author declares no conflict of interest.

Not applicable.

Malignant tumours pose significant challenges in terms of high morbidity and mortality rates, primarily due to the lack of large-scale applicable screening methods and efficient treatment strategies. However, the development of liquid biopsies, particularly circulating cell-free DNA (cfDNA), offers promising solutions characterised by their non-invasiveness and cost-effectiveness, providing comprehensive tumour information on a global scale. The release of cfDNA is predominantly associated with cell death and turnover, while its elimination occurs through nuclease digestion, renal excretion into the urine and uptake by the liver and spleen. Extensive research into the biological properties of cfDNA has led to the identification of novel applications, including non-invasive cancer screening, cancer subtype classification, tissue-of-origin detection and monitoring of treatment efficacy. Additionally, emerging fields such as methylation-omics, fragment-omics and nucleosome-omics show immense potential as tissue- and disease-specific markers. Therefore, this review aims to comprehensively introduce the latest detection techniques of cfDNA, along with detailed information on its characteristics and applications, providing valuable insights for cancer diagnosis and monitoring, which will assist us in purposefully enhancing relevant features for a more comprehensive application in clinical practice.

In this commentary, we briefly introduce the importance of metabolic reprogramming in non-small celllung cancer (NSCLC) and the role of aberrant glycolysis processes intumorigenesis and metastasis. We further summarize the regulation of deubiquitylation modification on glycolysis-related kinases in this system. Andwe discusse the major discovery the research by He Yuanming et al. published in Clinical and Translational Medicine.Their study demonstrates targeting the USP7-c-Abl-HK2 axis represents a promising therapeutic strategt for NSCLC.

Wet age-related macular degeneration (AMD) is a common cause of vision loss in the elderly. It is characterised by choroidal neovascularisation (CNV), caused by overexpression of vascular endothelial growth factor (VEGF), resulting in abnormal vessel proliferation. Current clinical management predominantly relies on anti-VEGF agents, which require frequent and costly injections. Clustered regularly interspaced short palindromic repeats (CRISPR) technology has emerged as a promising strategy for permanently suppressing angiogenesis by targeting the VEGF-related pathway. Increased research suggests that disrupting this pathway holds potential for preventing CNV progression. This review provides an overview of the aetiology, classification and pathophysiology of wet AMD, followed by a concise summary of current gene editing research using the CRISPR/Cas system via viral vector delivery strategies to target ocular pro-angiogenic factors, including Hif-1α, VEGF and VEGFR. The importance of timely targeting of VEGFA is emphasised and the challenges associated with gene editing therapies are also highlighted.