Human neurodevelopment is a complex process vulnerable to disruptions, particularly during the prenatal period. Maternal viral infections represent a significant environmental factor contributing to a spectrum of congenital defects with profound and enduring impacts on affected offspring. The advent of induced pluripotent stem cell (iPSC)-derived three-dimensional (3D) human brain organoids has revolutionised our ability to model prenatal viral infections and associated neurodevelopmental disorders. Notably, human brain organoids provide a distinct advantage over traditional animal models, whose brain structures and developmental processes differ markedly from those of humans. These organoids offer a sophisticated platform for investigating viral pathogenesis, infection mechanisms and potential therapeutic interventions, as demonstrated by their pivotal role during the 2016 Zika virus outbreak. This review critically examines the utilisation of brain organoids in elucidating the mechanisms of TORCH viral infections, their impact on human brain development and contribution to associated neurodevelopmental disorders.

Exercise-based cardiac rehabilitation is effective in improving cardiovascular disease risk factor management, cardiopulmonary function, and quality of life. However, the precise mechanisms underlying exercise-induced cardioprotection remain elusive. Recent studies have shed light on the beneficial functions of noncoding RNAs in either exercise or illness models, but only a limited number of noncoding RNAs have been studied in both contexts. Hence, the present study aimed to elucidate the pathophysiological implications and molecular mechanisms underlying the association among exercise, noncoding RNAs, and cardiovascular diseases. Additionally, the present study analysed the most effective and personalized exercise prescription, serving as a valuable reference for guiding the clinical implementation of cardiac rehabilitation in patients with cardiovascular diseases.

Leishmaniasis, caused by obligate intracellular Leishmania parasites, poses a significant global health burden. The control of Leishmania infection relies on an effective T cell-dependent immune response; however, various factors impede the host’s ability to mount a successful defence. Alterations in the chemokine profile, responsible for cell trafficking to the infection site, can disrupt optimal immune responses and influence the outcome of pathogenesis by facilitating parasite persistence. This review aims to emphasize the significance of the chemokine system in T cell responses and to summarize the current knowledge on the dysregulation of chemokines and their receptors associated with different subsets of T lymphocytes during Leishmaniasis. A comprehensive understanding of the dynamic nature of the chemokine system during Leishmaniasis is crucial for the development of successful immunotherapeutic approaches.

Glycosylation modifications of proteins and glycan hydrolysis are critical for protein function in biological processes. Aberrations in glycosylation enzymes are linked to lysosomal storage disorders (LSDs), immune interactions, congenital disorders and tumour progression. Mannosidase alpha class 2B member 1 (MAN2B1) is a lysosomal hydrolase from the α-mannosidase family. Dysfunction of MAN2B1 has been implicated as causative factors in mannosidosis, a lysosomal storage disorder characterised by cognitive impairment, hearing loss and immune system and skeletal anomalies. Despite decades of research, its role in pathogenic infections, autoimmune conditions, cancers and neurodegenerative pathologies is highly ambiguous. Future studies are required to shed more light on the intricate functioning of MAN2B1. To this end, we review the biological functions, expression patterns, enzymatic roles and potential implications of MAN2B1 across various cell types and disease contexts. Additionally, the novel insights presented in this review may aid in understanding the role of MAN2B1 in immune cells, thereby paving the way for targeted therapeutic interventions in immune-related disorders.

Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5′-nucleotidase (CD73/5′-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations to target cancer progression. In general, the adenosinergic axis has been linked to tumourigenic effects. However, CD73 can play contradictory effects, probably dependent on the tumour type, tumour microenvironment and tumour stage, thus being in some circumstances, inversely related to tumour progression. We herein reviewed the pathophysiological function of CD73 in cervical cancer and performed in silico analysis of the main components of the adenosinergic signalling in human tissues of cervical cancer compared to non-tumour cervix tissue. Our data showed that the NT5E gene, that encoded CD73, is hypermethylated, leading to a decreased CD73 expression in cervical cancer cells compared to normal cells. Consequently, the high availability of ADO cytoplasmatic/extracellular leads to its conversion to AMP by ADK, culminating in global hypermethylation. Therefore, epigenetic modulation may reveal a new role for CD73 in cervical cancer.

Acute pancreatitis (AP) is an acute-onset gastrointestinal disease characterized by a significant inflammation of the pancreas. Most of the time, AP does not leave substantial changes in the pancreas after the resolution of the symptoms but the severe forms are associated with local or systemic complications. The pathogenesis of AP has long been investigated and, lately, the importance of intracellular mechanisms and the immune system has been described. The initial modifications in AP take place in the acinar cell. There are multiple mechanisms by which cellular homeostasis is impaired, one of the most important being calcium overload. Necrotic pancreatic cells initiate the inflammatory response by secreting inflammatory mediators and attracting immune cells. From this point on, the inflammation is sustained by the involvement of innate and adaptive immune systems. Multiple studies have demonstrated the importance of the first 48 h for identifying patients at risk for developing severe forms. For this reason, there is a need to find new, easy-to-use and reliable markers for accurate predictions of these forms. This review provides an overview of the main pathogenetic mechanisms involved in AP development and the most promising biomarkers for severity stratification.

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.

Helicobacter pylori (H. pylori) is closely associated with gastric cancer and peptic ulcers. The effectiveness of antibiotic treatment against H. pylori is diminished by the emergence of drug-resistant strains, side effects, high cost and reinfections. Given the circumstances, it is imperative to develop a potent vaccination targeting H. pylori. Understanding H. pylori’s pathogenicity and the host’s immune response is essential to developing a vaccine. Furthermore, vaccine evaluation necessitates the careful selection of design formulation. This review article aims to provide a concise overview of the considerations involved in selecting the optimal antigen, adjuvant, vaccine delivery system and laboratory animal model for vaccine formulation. Furthermore, we will discuss some significant obstacles in the realm of developing a potent vaccination against H. pylori.

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.

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.

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.