Expert Reviews in Molecular Medicine最新文献

Background: Non-coding RNAs (ncRNAs) are transcribed RNA molecules that do not encode proteins but regulate diverse biological processes. Dysregulation of ncRNAs is implicated in cancer, where chemical modifications such as N6-methyladenosine (m6A), N4-acetylcytidine (ac4C), and glycosylation critically influence their function. However, these modifications, as precise regulators of ncRNA activity, have been less well-documented and understood in tumorigenesis and cancer progression.

Methods: This article systematically analyzes the roles of chemically modified ncRNAs - ribosomal RNA (rRNA), circular RNA (circRNA) and others - in cancer biology, synthesizingevidence from published studies on their mechanistic involvement in malignancy.

Results: We reveal how specific chemical modifications drive oncogenesis, impact cancer diagnosis, and affect therapeutic responses, while also exploring their prognostic potential. Furthermore, we highlight emerging connections between ncRNA epitranscriptomics and cancer.

Conclusions: This review provides novel insights into ncRNA epitranscriptomics as emerging biomarkers and intervention targets for precision oncology.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovial membrane, leading to cartilage destruction and bone erosion. Due to the complex pathogenesis of RA and the limitations of current therapies, increasing research attention has been directed towards novel strategies targeting fibroblast-like synoviocytes (FLS), which are key cellular components of the hyperplastic pannus. Recent studies have highlighted the pivotal role of FLS in the initiation and progression of RA, driven by their tumour-like transformation and the secretion of pro-inflammatory mediators, including cytokines, chemokines and matrix metalloproteinases. The aggressive phenotype of RA-FLS is marked by excessive proliferation, resistance to apoptosis, and enhanced migratory and invasive capacities. Consequently, FLS-targeted therapies represent a promising avenue for the development of next-generation RA treatments. The efficacy of such strategies - particularly those aimed at modulating FLS signalling pathways - has been demonstrated in both preclinical and clinical settings, underscoring their therapeutic potential. This review provides an updated overview of the pathogenic mechanisms and functional roles of FLS in RA, with a focus on critical signalling pathways under investigation, including Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NF-κB), Notch and interleukin-1 receptor-associated kinase 4 (IRAK4). In addition, we discuss the emerging understanding of FLS-subset-specific contributions to immunometabolism and explore how computational biology is shaping novel targeted therapeutic strategies. A deeper understanding of the molecular and functional heterogeneity of FLS may pave the way for more effective and precise therapeutic interventions in RA.

Background: Retinoic acid-induced 1 (RAI1) is a dosage-sensitive gene implicated in a range of rare neuropsychiatric diseases.

Methods: This review provides a comprehensive overview of RAI1's role, integrating both clinical and basic research on Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) while also summarising research progress on its involvement in spinocerebellar ataxia (SCA), autism spectrum disorder (ASD), schizophrenia, bipolar disorder and major depression. A systematic review of the literature was conducted using PubMed and EMBASE, following the PRISMA guidelines, with the protocol registered in PROSPERO (CRD42023474165).

Results: A total of 99 eligible studies on RAI1 were included. We presented detailed characterisations of SMS and PTLS patients, emphasising the crucial role of RAI1 haploinsufficiency and overexpression in their pathogenesis. Additionally, we summarised research progress on RAI1 in SCA, ASD, schizophrenia, bipolar disorder and major depression. Integrating findings from animal studies, particularly those examining the regulatory mechanisms of RAI1 in critical phenotypes, such as body weight, sleep and epilepsy, underscores the precise regulation of RAI1 expression in maintaining various nervous system functions.

Conclusions: Overall, this review contributes to the identification of RAI1-related neuropsychiatric diseases, with a particular emphasis on enhancing clinical diagnosis of SMS and PTLS in developing countries.

Genome editing has recently evolved from a theoretical concept to a powerful and versatile set of tools. The discovery and implementation of CRISPR-Cas9 technology have propelled the field further into a new era. This RNA-guided system allows for specific modification of target genes, offering high accuracy and efficiency. Encouraging results are being announced in clinical trials employed in conditions like sickle cell disease (SCD) and transfusion-dependent beta-thalassaemia (TDT). The path finally led the way to the recent FDA approval of the first gene therapy drug utilising the CRISPR/Cas9 system to edit autologous CD34+ haematopoietic stem cells in SCD patients (Casgevy). Ongoing research explores the potential of CRISPR technology for cancer therapies, HIV treatment and other complex diseases. Despite its remarkable potential, CRISPR technology faces challenges such as off-target effects, suboptimal delivery systems, long-term safety concerns, scalability, ethical dilemmas and potential repercussions of genetic alterations, particularly in the case of germline editing. Here, we examine the transformative role of CRISPR technologies, including base editing and prime editing approaches, in modifying the genetic and epigenetic codes in the human genome and provide a comprehensive focus, particularly on relevant clinical applications, to unlock the full potential and challenges of gene editing.

Leishmaniasis, classified as a neglected tropical disease, exerts its impact on millions globally. Its clinical spectrum encompasses diverse forms, from benign self-resolving skin lesions (cutaneous leishmaniasis) to life-threatening visceral infections (visceral leishmaniasis or kala-azar). This review aims to comprehensively explore the spectrum of the disease as an outcome of often-overlooked parasite variants. Additionally, it addresses the emerging challenges faced in the pursuit towards disease elimination. The evolving landscape of leishmaniasis demands the development of molecular surveillance tools to detect the heterogeneous parasite strains that contribute to the emergence of new endemic foci. Such surveillance poses formidable challenges to current elimination strategies. As the disease landscape continues to evolve, understanding the molecular intricacies of causative parasite strains becomes paramount. This knowledge not only aids the understanding of the basis of emerging/shifting endemic areas but also facilitates the search for and the design of targeted interventions. In this context, this review will navigate through the dynamic terrain of leishmaniasis, the various causative species of Leishmania parasites emphasising the urgency for the development of robust surveillance mechanisms and innovative approaches to confront the evolving challenges in our quest for global disease elimination.

Background: The recent emergence of three-dimensional organoids and their utilization as in vitro disease models confirmed the complexities behind organ-specific functions and unravelled the importance of establishing suitable human models for various applications. Also, in light of persistent challenges associated with their use, researchers have been striving to establish more advanced structures (i.e. assembloids) that can help address the limitations presented in the current organoids.

Methods: In this review, we discuss the distinct organoid types that are available to date, with a special focus on retinal and brain organoids, and highlight their importance in disease modelling.

Results: We refer to published research to explore the extent to which retinal and brain organoids can serve as potential alternatives to organ/cell transplants and direct our attention to the topic of photostimulation in retinal organoids. Additionally, we discuss the advantages of incorporating microfluidics and organ-on-a-chip devices for boosting retinal organoid performance. The challenges of organoids leading to the subsequent development of assembloid fusion models are also presented.

Conclusion: In conclusion, organoid technology has laid the foundation for generating upgraded models that not only better replicate in vivo systems but also allow for a deeper comprehension of disease pathophysiology.

Background: The global incidences of leishmaniasis are increasing due to changing environmental conditions and growing poverty. Leishmaniasis, caused by the Leishmania parasite, presents itself in six different clinical forms, the cutaneous and the visceral diseases being the most prevalent. While the cutaneous form causes disfigurement, the visceral form could be fatal if not treated. With no available vaccines combined with serious side effects of current medications and emerging drug resistance, it is crucial to discover new drugs whether as novel compounds or as repurposed existing pharmaceuticals. In the realm of drug development, mitochondria are recognized as important pharmacological targets due to their critical role in energy control, which, when disrupted, leads to irreversible cell damage. Certain plant-based compounds able to target the parasite mitochondrion, have been studied for their potential anti-leishmanial effects.

Search results: These compounds have shown promising effects in eliminating the Leishmania parasite. Artemisinin and chloroquine, two anti-malarial drugs that target mitochondria, exert strong anti-leishmanial effectiveness in both in vitro cultures and in vivo animal models. Quinolones, coumarins and quercetin are other compounds with leishmanicidal properties, which disrupt mitochondrial activity to effectively eliminate parasites in animal models of the disease and could be considered as potential drugs.

Conclusions: Therefore, plant-based compounds hold promise as potential candidates for anti-leishmanial drug development.

The undeniable impact of climate change and air pollution on respiratory health has led to increasing cases of asthma, allergic rhinitis and other chronic non-communicable immune-mediated upper and lower airway diseases. Natural bioaerosols, such as pollen and fungi, are essential atmospheric components undergoing significant structural and functional changes due to industrial pollution and atmospheric warming. Pollutants like particulate matter(PMx), polycyclic aromatic hydrocarbons(PAHs), nitrogen dioxide(NO₂), sulfur dioxide(SO₂) and carbon monoxide(CO) modify the surface and biological properties of atmospheric bioaerosols such as pollen and fungi, enhancing their allergenic potentials. As a result, sensitized individuals face heightened risks of asthma exacerbation, and these alterations likely contribute to the rise in frequency and severity of allergic diseases. NAMs, such as precision-cut lung slices(PCLS), air-liquid interface(ALI) cultures and lung-on-a-chip models, along with the integration of data from these innovative models with computational models, provide better insights into how environmental factors influence asthma and allergic diseases compared to traditional models. These systems simulate the interaction between pollutants and the respiratory system with higher precision, helping to better understand the health implications of bioaerosol exposure. Additionally, NAMs improve preclinical study outcomes by offering higher throughput, reduced costs and greater reproducibility, enhancing the translation of data into clinical applications. This review critically evaluates the potential of NAMs in researching airway diseases, with a focus on allergy and asthma. It highlights their advantages in studying the increasingly complex structures of bioaerosols under conditions of environmental pollution and climate change, while also addressing the existing gaps, challenges and limitations of these models.

MicroRNAs have emerged as effective biomarkers in disease diagnostics, particularly cancer, due to their role as regulatory sequences. More recently, microRNAs have been detected in liquid biopsies, which hold immense potential for early disease diagnostics. This review comprehensively analyses distinct liquid biopsy microRNA detection methods validated with clinical samples. Each step in the microRNA detection workflow, including sample collection, RNA isolation, processing, and detection of target microRNAs, has been thoroughly assessed. The review discusses the advantages and limitations of established and novel techniques in microRNA detection workflows, discussing their diagnostic capabilities and potential for future implementation at scale.