CD19 CAR-T cell therapy: a new dawn for autoimmune rheumatic diseases?

Autoimmune rheumatic diseases (ARDs), such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, involve dysregulated immune responses causing chronic inflammation and tissue damage. Despite advancements in clinical management, many patients do not respond to current treatments, which often show limited efficacy due to the persistence of autoreactive B cells. Chimeric antigen receptor (CAR)-T cell therapy, which has shown success in oncology for B cell malignancies, targets specific antigens and involves the adoptive transfer of genetically engineered T cells.

Evaluating MicroRNAs as Diagnostic Tools for Lymph Node Metastasis in Breast Cancer: Findings from a Systematic Review and Meta-Analysis.

Lymph node metastasis (LNM) significantly affects the prognosis and clinical management of breast cancer (BC) patients. This systematic review and meta-analysis aim to identify microRNAs (miRNAs) associated with LNM in BC and evaluate their potential diagnostic and prognostic value. Following PRISMA guidelines, a comprehensive literature search was conducted in PubMed, Web of Science, and SCOPUS databases, to assess the role of miRNAs in LNM BC.

Click chemistry-based dual nanosystem for microRNA-122 detection with single-base specificity from tumour cells.

MicroRNAs (miRNAs) have been recognised as potential biomarkers due to their specific expression patterns in different biological tissues and their changes in expression under pathological conditions. MicroRNA-122 (miR-122) is a vertebrate-specific miRNA that is predominantly expressed in the liver and plays an important role in liver metabolism and development. Dysregulation of miR-122 expression is associated with several liver-related diseases, including hepatocellular carcinoma and drug-induced liver injury (DILI).

First-in-class transactivator-free, doxycycline-inducible IL-18-engineered CAR-T cells for relapsed/refractory B cell lymphomas.

Although chimeric antigen receptor (CAR) T cell therapy has revolutionized type B cancer treatment, efficacy remains limited in various lymphomas and solid tumors. Reinforcing conventional CAR-T cells to release cytokines can improve their efficacy but also increase safety concerns. Several strategies have been developed to regulate their secretion using minimal promoters that are controlled by chimeric proteins harboring transactivators.

Pheno-Ranker: a toolkit for comparison of phenotypic data stored in GA4GH standards and beyond.

Background: Phenotypic data comparison is essential for disease association studies, patient stratification, and genotype-phenotype correlation analysis. To support these efforts, the Global Alliance for Genomics and Health (GA4GH) established Phenopackets v2 and Beacon v2 standards for storing, sharing, and discovering genomic and phenotypic data. These standards provide a consistent framework for organizing biological data, simplifying their transformation into computer-friendly formats.

Complex immune network and regional consistency in the human gastric mucosa revealed by high-resolution spectral cytometry.

The immune cellular landscape from the gastric mucosa remains largely unknown despite its relevance in several inflammatory conditions. Human gastric biopsies were obtained from the antrum, body and incisura from 10 individuals to obtain lamina propria mononuclear cells that were further characterized by spectral cytometry. Phenotypic hierarchical analyses identified a total of 52 different immune cell subsets within the human gastric mucosa revealing that T-cells (> 60%) and NK cells (> 20%) were the main populations.

Oxidation-sensitive cysteines drive IL-38 amyloid formation.

Interleukin (IL)-1 family cytokines are essential for host defense at epithelial barriers. The IL-1 family member IL-33 was recently linked to stress granules (SGs). Formation of SGs and other biomolecular condensates is promoted by proteins containing low-complexity regions (LCRs).

Exploring the role of genetic variability and exposure to bisphenols and parabens on excess body weight in Spanish children.

Gene-environment interaction studies are emerging as a promising tool to shed light on the reasons for the rapid increase in excess body weight (overweight and obesity). We aimed to investigate the influence of several polymorphisms on excess weight in Spanish children according to a short- and long-term exposure to bisphenols and parabens, combining individual approach with the joint effect of them. This case-control study included 144 controls and 98 cases children aged 3-12 years.

Resectable Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization.

Introduction: Non-small cell lung cancer (NSCLC) is the most common type of lung neoplasm. Despite surgical resection, it has a high relapse rate, accounting for 30-55% of all cases. Next-generation sequencing (NGS) based on a customized gene panel and the analysis of circulating tumor cells (CTCs) can help identify heterogeneity, stratify high-risk patients, and guide treatment decisions.

Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BID variant with an increased risk of developing the disease (OR = 1.

Identification of SYNJ1 in a Complex Case of Juvenile Parkinsonism Using a Multiomics Approach.

This study aimed to elucidate the genetic causes underlying the juvenile parkinsonism (JP) diagnosed in a girl with several family members diagnosed with spinocerebellar ataxia type 2 (SCA2). To achieve this, whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification were performed. As a result, a homozygous missense mutation SNP T>C (rs2254562) in synaptojamin 1 (SYNJ1), which has been implicated in the regulation of membrane trafficking in the synaptic vesicles, was identified.

The T-cell repertoire of Spanish patients with COVID-19 as a strategy to link T-cell characteristics to the severity of the disease.

Background: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients.

Methods: The cohort included 98 mild and 75 severe cases with a median age of 53.

Influence of Genetic Polymorphisms on Cognitive Function According to Dietary Exposure to Bisphenols in a Sample of Spanish Schoolchildren.

Background: Neurodevelopmental disorders (NDDs) like intellectual disability (ID) are highly heritable, but the environment plays an important role. For example, endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and its analogues, have been termed neuroendocrine disruptors. This study aimed to evaluate the influence of different genetic polymorphisms (SNPs) on cognitive function in Spanish schoolchildren according to dietary bisphenol exposure.

Multiomics and eXplainable artificial intelligence for decision support in insulin resistance early diagnosis: A pediatric population-based longitudinal study.

Pediatric obesity can drastically heighten the risk of cardiometabolic alterations later in life, with insulin resistance standing as the cornerstone linking adiposity to the increased cardiovascular risk. Puberty has been pointed out as a critical stage after which obesity-associated insulin resistance is more difficult to revert. Timely prediction of insulin resistance in pediatric obesity is therefore vital for mitigating the risk of its associated comorbidities.

EZH2 represses mesenchymal genes and upholds the epithelial state of breast carcinoma cells.

Emerging studies support that the polycomb repressive complex 2 (PRC2) regulates phenotypic changes of carcinoma cells by modulating their shifts among metastable states within the epithelial and mesenchymal spectrum. This new role of PRC2 in cancer has been recently proposed to stem from the ability of its catalytic subunit EZH2 to bind and modulate the transcription of mesenchymal genes during epithelial-mesenchymal transition (EMT) in lung cancer cells. Here, we asked whether this mechanism is conserved in other types of carcinomas.

Unveiling the impact of circulating tumor cells: Two decades of discovery and clinical advancements in solid tumors.

Circulating tumor cells (CTCs) enumeration and molecular profiling hold promise in revolutionizing the management of solid tumors. Their understanding has evolved significantly over the past two decades, encompassing pivotal biological discoveries and clinical studies across various malignancies. While for some tumor types, such as breast, prostate, and colorectal cancer, CTCs are ready to enter clinical practice, for others, additional research is required.

Analysis of HLA Alleles in Different Cohorts of Patients Infected by from Southern Spain.

Leishmaniasis is an infectious disease caused by protozoa of the genus , which is endemic in certain areas of Europe, such as southern Spain. The disease manifests in various clinical phenotypes, including visceral, cutaneous, mucosal, or asymptomatic leishmaniasis. This diversity in clinical outcomes may be influenced by the host immune response, with human leukocyte antigen (HLA) molecules playing a crucial role in determining susceptibility and progression of the infection.

MiRNA expression as outcome predictor in pediatric AML: systematic evaluation of a new model.

Accurately predicting patient outcomes is essential for optimizing treatment and improving outcomes in pediatric acute myeloid leukemia (AML). In recent years, microRNAs have emerged as a promising prognostic marker, with a growing body of evidence supporting their potential predictive value. We systematically reviewed all previous studies that have analyzed the expression of microRNAs as predictors of survival in pediatric AML and found 16 microRNAs and 4 microRNA signatures previously proposed as predictors of survival.

NG2 is a target gene of MLL-AF4 and underlies glucocorticoid resistance in MLLr B-ALL by regulating NR3C1 expression.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, with long-term overall survival rates of ∼85%. However, B-ALL harboring rearrangements of the MLL gene (also known as KMT2A), referred to as MLLr B-ALL, is common in infants and is associated with poor 5-year survival, relapses, and refractoriness to glucocorticoids (GCs). GCs are an essential part of the treatment backbone for B-ALL, and GC resistance is a major clinical predictor of poor outcome.