Pius N. Nde

P-element–induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a distinct class of small non-coding RNAs increasingly recognized as regulators of gene expression beyond their canonical function in PIWI-dependent transposon silencing. First characterized in the germline, recent evidence demonstrates that PIWI–piRNA pathways are active in somatic tissues and contribute to cellular homeostasis and adaptive stress responses through epigenetic, transcriptional, post-transcriptional, and translational mechanisms. Although piRNAs regulate several diseases, their roles in ocular physiology and pathology remain poorly understood. In the eye, piRNA pathways may govern retinal homeostasis and responses to oxidative stress, inflammation, angiogenesis, and fibrosis. This review synthesizes current knowledge on piRNA biogenesis, molecular mechanisms, and emerging functions in ocular tissues and examines evidence linking PIWI–piRNA dysregulation to major ocular diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and subretinal fibrosis. We evaluate the current evidence and highlight that, although disease-associated piRNA signatures and emerging mechanistic links to angiogenesis, oxidative stress, fibrosis, and cellular stress responses have been reported, most findings remain correlative and lack physiological validation. We discuss key challenges, including incomplete piRNA annotation, cell-type-specific activity, and variability in PIWI–piRNA regulatory mechanisms. We also outline future perspectives for defining the roles of PIWI–piRNA networks in ocular physiology and evaluating their potential as biomarkers and therapeutic targets for vision-threatening diseases.

Contemporary breast cancer treatments include chemotherapy, surgery, and radiation therapy, all of which are invasive or accompanied by severe side effects. Although emerging research suggests that parasites have unique features that may be capitalized to develop innovative cancer treatments, the idea of using parasites for therapeutic purposes has been around for more than 3,500 yr. Parasites constitute a novel source of biomolecules with potent immunomodulatory and antitumor properties. This review summarizes our current knowledge on how components of the host response to parasite infection, specifically the inflammatory response, could be exploited to develop novel therapeutics for breast cancer. By identifying the molecular mechanisms behind parasite-induced antitumor properties, pathogen biomolecules could be potentially used as effective therapeutic alternatives or additives against breast cancer.

We describe methods for developing a high-throughput, label-free quantitative proteomics workflow integrated with physiological and clinical assessments to investigate cardiovascular disease mechanisms and identify potential biomarkers. This resource outlines a validated, longitudinal plasma proteomics pipeline—including data quality controls, statistical testing, and biological validation—applied to over 500 samples from the N-TA ³ CT trial, offering a reproducible framework for future biomarker discovery studies.

When blood flow to a part of the myocardial muscle is reduced or blocked, it leads to tissue ischemia in that region. Myocardial infarction (MI) occurs when the ischemic insult is of sufficient duration in time to induce cardiomyocyte death and subsequent activation of the innate immune response. MI initiates a complex cascade of cellular and molecular events within the left ventricle. Inflammatory cells rapidly infiltrate the infarcted area to remove necrotic tissue, setting the stage for reparative wound healing processes. Over the ensuing days, various cell populations—including leukocytes, fibroblasts, and endothelial cells—are attracted to the infarcted site by inflammatory cytokines and chemokines. The activated cells at the site of injury contribute to tissue remodeling and scar formation through the deposition of extracellular matrix components, particularly collagen. While scar formation is essential for structural stabilization of the infarct region to replace the loss of cardiomyocytes, scar tissue also increases myocardial stiffness and impairs cardiac contractile function. This review summarizes our knowledge regarding cellular dynamics, inflammatory signaling, and cardiac remodeling that govern MI healing. We identify the current gaps in the field and provide a foundational resource for those seeking to understand the biological underpinnings of cardiac repair following MI.

Cardiovascular disease remains the number one cause of death worldwide. Across the spectrum of cardiovascular pathologies, all are accompanied by changes in gene expression profiles spanning a variety of cellular components of the myocardium. Alterations in gene expression are regulated by small noncoding RNAs (sncRNAs), with P-element-induced WImpy testis (PIWI)-interacting RNAs (piRNAs) being the most abundant of the sncRNAs in the human genome. Composed of 21–35 nucleotides in length with a protective methyl group at the 3′ end, piRNAs complex with highly conserved RNA-binding proteins termed PIWI proteins to recruit enzymes used for histone, DNA, RNA, and protein modifications. Thus, specific piRNA expression patterns can be exploited for early clinical diagnosis of cardiovascular disease and the development of novel RNA therapeutics that may improve cardiac health outcomes. This review summarizes the latest progress made on understanding how piRNAs regulate cardiovascular health and disease progression, including a discussion of their potential in the development of biomarkers and therapeutics.

Trypanosoma cruzi, the etiological agent of Chagas Disease, causes severe morbidity, mortality, and economic burden worldwide. Though originally endemic to Central and South America, globalization has led to increased parasite presence in most industrialized countries. About 40% of infected individuals will develop cardiovascular, neurological, and/or gastrointestinal pathologies. Accumulating evidence suggests that the parasite induces alterations in host gene expression profiles in order to facilitate infection and pathogenesis. The role of regulatory gene expression machinery duringT. cruziinfection, particularly small noncoding RNAs, has yet to be elucidated. In this study, we aim to evaluate dysregulation of a class of sncRNAs called piRNAs during early phase ofT. cruziinfection in primary human cardiac fibroblasts by RNA-Seq. We subsequently performedin silicoanalysis to predict piRNA-mRNA interactions. We validated the expression of these selected piRNAs and their targets during early parasite infection phase by stem loop qPCR and qPCR, respectively. We found about 26,496,863 clean reads (92.72%) which mapped to the human reference genome. During parasite challenge, 441 unique piRNAs were differentially expressed. Of these differentially expressed piRNAs, 29 were known and 412 were novel. In silico analysis showed several of these piRNAs were computationally predicted to target and potentially regulate expression of genes includingSMAD2, EGR1, ICAM1, CX3CL1, andCXCR2, which have been implicated in parasite infection, pathogenesis, and various cardiomyopathies. Further evaluation of the function of these individual piRNAs in gene regulation and expression will enhance our understanding of early molecular mechanisms contributing to infection and pathogenesis. Our findings here suggest that piRNAs play important roles in infectious disease pathogenesis and can serve as potential biomarkers and therapeutic targets.

New bronchopulmonary dysplasia (BPD) is a neonatal disease that is theorized to begin in utero and manifests as reduced alveolarization due to inflammation of the lung. Risk factors for new BPD in human infants include intrauterine growth restriction (IUGR), premature birth (PTB) and formula feeding. Using a mouse model, our group recently reported that a paternal history of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure increased his offspring’s risk of IUGR, PTB, and new BPD. Additionally, formula supplementation of these neonates worsened the severity of pulmonary disease. In a separate study, we reported that a paternal preconception fish oil diet prevented TCDD-driven IUGR and PTB. Not surprisingly, eliminating these two major risk factors for new BPD also significantly reduced development of neonatal lung disease. However, this prior study did not examine the potential mechanism for fish oil’s protective effect. Herein, we sought to determine whether a paternal preconception fish oil diet attenuated toxicant-associated lung inflammation, which is an important contributor to the pathogenesis of new BPD. Compared to offspring of standard diet TCDD-exposed males, offspring of TCDD-exposed males provided a fish oil diet prior to conception exhibited a significant reduction in pulmonary expression of multiple pro-inflammatory mediators (Tlr4, Cxcr2, Il-1 alpha). Additionally, neonatal lungs of pups born to fish oil treated fathers exhibited minimal hemorrhaging or edema. Currently, prevention of BPD is largely focused on maternal strategies to improve health (e.g., smoking cessation) or reduce risk of PTB (e.g., progesterone supplementation). Our studies in mice support a role for also targeting paternal factors to improve pregnancy outcomes and child health.