Psoriasis vulgaris and other chronic inflammatory diseases improve markedly with therapeutic blockade of interleukin-23 (IL-23) signaling, but the genetic mechanisms underlying clinical responses remain poorly understood. Using single-cell transcriptomics, we profiled immune cells isolated from lesional psoriatic skin before and during IL-23 blockade. In clinically responsive patients, a psoriatic transcriptional signature in skin-resident memory T cells was strongly attenuated. In contrast, poorly responsive patients were distinguished by persistent activation of IL-17–producing T (T17) cells, a mechanism distinct from alternative cytokine signaling or resistance isolated to epidermal keratinocytes. Even in IL-23 blockade–responsive patients, we detected a recurring set of recalcitrant, disease-specific transcriptional abnormalities. This irreversible immunological state may necessitate ongoing IL-23 inhibition. Spatial transcriptomic analyses also suggested that successful IL-23 blockade requires dampening of >90% of IL-17–induced response in lymphocyte-adjacent keratinocytes, an unexpectedly high threshold. Collectively, our data establish a patient-level paradigm for dissecting responses to immunomodulatory treatments.

Colorectal cancer (CRC) is one of the most common cancer types, ranking third after lung and breast cancers. As such, it demands special attention for better characterization, which may eventually result in the development of early detection strategies and preventive measures. Currently, components of bodily fluids, which may reflect various disease states, are being increasingly researched for their biomarker potential. One of these components is the circulating extracellular vesicles, namely, exosomes, which are demonstrated to carry various cargo. Of importance, the non-coding RNA cargo of circulating exosomes, especially long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and micro RNAs (miRNAs), may potentially serve as significant diagnostic and prognostic/predictive biomarkers. In this review, we present existing evidence on the diagnostic and prognostic/predictive biomarker value of exosomal non-coding RNAs in CRC. In addition, taking advantage of the miRNA sponging functionality of lncRNAs and circRNAs, we demonstrate an experimentally validated CRC exosomal non-coding RNA-regulated target gene axis benefiting from published miRNA sponging studies in CRC. Hence, we present a set of target genes and pathways downstream of the lncRNA/circRNA–miRNA–target axis along with associated significant Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may collectively serve to better characterize CRC and shed light on the significance of exosomal non-coding RNAs in CRC diagnosis and prognosis/prediction.

Breast cancer (BC) remains a significant global health issue, necessitating advanced molecular approaches for early detection and prevention. This review delves into the roles of microRNAs (miRNAs) and circular RNAs (circRNAs) in BC, highlighting their potential as non-invasive biomarkers. Utilizing in silico tools and databases, we propose a novel methodology to establish mRNA/circRNA/miRNA axes possibly indicative of early detection and possible prevention. We propose that during early tumor initiation, some changes in oncogene or tumor suppressor gene expression (mRNA) are mirrored by alterations in corresponding circRNAs and reciprocal changes in sponged miRNAs affecting tumorigenesis pathways. We used two Gene Expression Omnibus (GEO) datasets and identified five mRNA/circRNA/miRNA axes as early possible tumor initiation biomarkers. We further validated the proposed axes through a Kaplan–Meier (KM) plot and enrichment analysis of miRNA expression using patient data. Evaluating coupled differential expression of circRNAs and miRNAs in body fluids or exosomes provides greater confidence than assessing either, with more axes providing even greater confidence. The proposed methodology not only improves early BC detection reliability but also has applications for other cancers, enhancing preventive measures.

Acute gastroenteritis (AGE) is associated with significant global morbidity and mortality, especially among children under five years of age. Viruses are well established as etiologic agents of gastroenteritis since they are the most common pathogens that contribute to the disease burden in developing countries. Despite the advances in molecular diagnosis, a substantial proportion of AGE etiology remain unresolved. We implemented a viral metagenomics pipeline to determine the potential viral etiology associated with AGE among children under the age of five years in Qatar with undiagnosed etiology. Following enriching for the viral genome, ∼1.3 billion sequences were generated from 89 stool specimens using the Illumina HiSeq platform, of which 7% were mapped to viral genomes. Human viruses were detected in 34 specimens (38.2%); 14 were adenovirus, nine coxsackievirus A16, five rotavirus (G9P[8] and G4P[8]), four norovirus (GII), one influenza A virus (H3), and one respiratory syncytial virus A (RSVA). In conclusion, the viral metagenomics approach is useful for determining AGE's etiology when routine molecular diagnostic assays fail.

Breast cancer (BC), the most prevalent cancer in women, is a heterogenous disease. Despite advancements in BC diagnosis, prognosis, and therapeutics, survival rates have drastically decreased in the metastatic setting. Therefore, BC still remains a medical challenge. The evolution of high-throughput technology has highlighted gaps in the classification system of BCs. Of particular interest is the notorious triple negative BC, which was recounted as being heterogenous itself and it overlaps with distinct subtypes, namely molecular apocrine (MA) and luminal androgen (LAR) BCs. These subtypes are, even today, still misdiagnosed and poorly treated. As such, researchers and clinicians have been looking for ways through which to refine BC classification in order to properly understand the initiation, development, progression, and the responses to the treatment of BCs. One tool is biomarkers and, specifically, microRNA (miRNA), which are highly reported as associated with BC carcinogenesis. In this review, the diverse roles of miRNA in estrogen receptor negative (ER−) and androgen receptor positive (AR+) BC are depicted. While highlighting their oncogenic and tumor suppressor functions in tumor progression, we will discuss their diagnostic, prognostic, and predictive biomarker potentials, as well as their drug sensitivity/resistance activity. The association of several miRNAs in the KEGG-reported pathways that are related to ER-BC carcinogenesis is presented. The identification and verification of accurate miRNA panels is a cornerstone for tackling BC classification setbacks, as is also the deciphering of the carcinogenesis regulators of ER − AR + BC.