Search Results (2,427)

In recent decades, there has been a significant amount of research on the biological role of non-coding RNAs (ncRNAs) in both normal and pathological conditions. Specifically, a growing body of evidence suggests that ncRNAs play a crucial role in maintaining epidermal homeostasis. These ncRNAs are involved in regulating epidermal differentiation and wound healing, as well as in pathological skin conditions, such as psoriasis and chronic wounds. The discovery of mechanisms such as RNA interference and other modes of action of ncRNAs has led to the development of novel therapeutic strategies, where ncRNAs could serve as targets, therapeutic agents, or diagnostic markers. This review explores the role of different classes of ncRNAs in the epidermis under normal and abnormal conditions, the mechanisms by which ncRNAs interact with other modulators of epidermal homeostasis, and the current state of ncRNA-based therapy. Full article

This study conducted a bioinformatic analysis of two Hyaluronidase-like isoforms (Mn-HyaL1 and Mn-HyaL2) in Macrobrachium nipponense and investigated their phylogenetic relationships. The open reading frames of Mn-HyaL1 and Mn-HyaL2 were 1101 bp (encoding 366 amino acids) and 1164 bp (encoding 387 amino acids), respectively. Both isoforms exhibited similar conserved domains, with an amino acid sequence similarity of 60.21%. Quantitative PCR analysis revealed that the expression levels of Mn-HyaL1 and Mn-HyaL2 increased during the mid-to-late phase of each developmental stage, were higher during the reproductive season than in the non-reproductive season, and were more abundant in the hepatopancreas than in other tissues. RNA interference experiments targeting both genes simultaneously demonstrated that knockdown of Mn-HyaL2 significantly accelerated ovarian development in M. nipponense, indicating that Mn-HyaL genes function as negative regulators of ovarian maturation. A comparative analysis of multiple genes revealed the following descending order of potency in promoting ovarian development in M. nipponense: Mn-Cholesterol 7-desaturase > Mn-Cathepsin L1. The order of potency in inhibiting ovarian development in M. nipponense, from strongest to weakest, was determined to be Mn-Gonad-inhibiting hormone > Mn-HyaL2. Full article

Secondhand smoke (SHS), found in about 57.6% of global public areas as a widespread environmental hazard, has been associated with negative effects during pregnancy, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Our research investigated the impact of SHS on placental issues in a C57BL/6 model that simulates PE and IUGR in mice. We administered SHS to pregnant mice through a nose-only delivery method, beginning either on embryonic day 12.5 (prior to spiral artery (SA) invasion; labeled SHS-6D) or day 14.5 (following SA invasion; labeled SHS-4D), continuing up to E18.5. Control animals received only ambient air. We employed bulk RNA sequencing to assess and describe changes in placental gene expression patterns. For the SHS-4D group, which mimicked IUGR, compared to untreated controls, results showed elevated levels of inflammation-related genes (IL11RA, CHI3L1) alongside likely interference in pathways for antibody-triggered complement activation, marked by reduced expression of C1QA, C1QB, and C1QC. Immune profiling also indicated decreased macrophage activity in the placentas of the SHS-4D group relative to those from normal pregnancies at term. In contrast, the SHS-6D versus control analysis revealed lowered expression of collagen-related genes (COL1A1, COL4A5, COL4A6, COL17A1). Additionally, SHS-6D exhibited higher levels of genes associated with cell-based lysis processes compared to SHS-4D. An evaluation of the existing literature revealed that nearly every differentially expressed gene (DEG) identified in our work has been reported in studies associated with SHS exposure. Yet, few of these DEGs are discussed alongside PE or IUGR in prior reports, highlighting gaps in knowledge about how SHS triggers these conditions. Overall, we determined that the timing of SHS exposure in pregnant mice results in unique patterns of gene regulation and involvement in biological pathways. Full article

Endocrine-disrupting chemicals (EDCs) are widespread contaminants that interfere with hormonal signaling and compromise reproductive success in aquatic organisms. Vitellogenin (VTG) is one of the most widely established biomarkers of estrogenic exposure, especially in males and juveniles. However, evidence from multi-omics studies indicates that VTG induction occurs within broader transcriptional and regulatory networks, involving genes such as cyp19a1 (aromatase), cyp1a (cytochrome P4501A), and other stress-responsive genes, underscoring the complexity of endocrine disruption. This review focuses on nuclear receptor isoforms, including estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and androgen receptor (AR) variants. We examine the diversification of vtg gene repertoires across teleost genomes and epigenetic mechanisms, such as DNA methylation and microRNAs, that modulate sex-dependent sensitivity. In addition, we discuss integrative approaches that combine VTG with transcriptomic, epigenetic, and histological endpoints. Within the Adverse Outcome Pathway (AOP) and weight-of-evidence (WoE) frameworks, these strategies provide mechanistic links between receptor activation and reproductive impairment. Finally, we outline future directions, focusing on the development of sex-specific biomarker panels, the integration of omics-based data with machine learning, and advances in ecogenomics. Embedding molecular responses into ecological and regulatory contexts will help bridge mechanistic insights with environmental relevance and support sustainability goals such as SDG 14 (Life Below Water). Full article

White Spot Syndrome Virus (WSSV) is one of the most devastating viral pathogens affecting shrimp, causing severe economic losses to the global farmed shrimp trade. The globalization of live shrimp trade and waterborne transmission have facilitated the rapid spread of WSSV across major shrimp-producing countries since its initial emergence. The present review gives an updated account of WSSV biology, pathology, transmission dynamics, and recent developments in control measures. The virus, a double-stranded DNA virus of the Nimaviridae family, utilizes advanced immune evasion strategies, resulting in severe mortality. Shrimp lack adaptive immunity and hence rely predominantly on innate immunity, which is insufficient to mount an effective response against severe infections. Traditional disease control measures such as augmented biosecurity, selective breeding, and immunostimulants have, despite extensive research, achieved only limited success. New biotechnological tools such as RNA interference, CRISPR-Cas gene editing, and nanotechnology offer tremendous potential for disease mitigation. In parallel, the development of DNA and RNA vaccines targeting WSSV structural proteins, such as VP28, holds significant promise for stimulating the shrimp immune system. This review highlights the urgent need for a convergent approach to sustainable disease management in global shrimp aquaculture, with interdisciplinarity playing a pivotal role in shaping the future of WSSV control. Full article

BIRC6, a member of the inhibitor of apoptosis protein family (IAP), regulates apoptosis, autophagy and cytokinesis. IAPs are often overexpressed in tumors, contributing to oncogenesis, therapy resistance and worse prognosis. In particular, BIRC6 overexpression has been found in several tumor tissues. The aim of this study was to evaluate the effect of BIRC6 silencing on the apoptotic response of breast and lung tumor cells. We used RNA interference based on short hairpin RNA (shRNA) to knock down gene expression encoded by a recombinant baculovirus (BV), an insect-specific virus unable to replicate in mammalian hosts, to carry out preclinical validation tests in experimental models both in vitro and in vivo. Our results indicate that BIRC6 plays an antiapoptotic role in both breast and lung tumor cells. In vivo, treatment with BV-shBRIC6 reduced breast and lung tumor progression and increased overall survival. After histological analysis, BV-shBRIC6 was able to increase tumor necrosis. In addition, we demonstrated that BIRC6 expression correlates with antiapoptotic and tumor progression-relevant markers in lung and breast cancer patients. BV-based silencing of BIRC6 may have therapeutic value for the treatment of lung and breast tumors. Further translational studies of BV-shBIRC6 in lung and breast cancer are warranted. Full article

Endometriosis is a common gynecological condition that affects fertility in many women of reproductive age worldwide. This multifaceted disease exhibits a pathogenesis characterized by hormonal and immune system dysregulations, alongside increased angiogenic activity within the peritoneum. The aberrant proliferation of endometrial tissue outside the uterus is associated with vascularization in ectopic endometriotic lesions. Consequently, RNA interference (RNAi)-based angiogenic therapies targeting the VEGFA gene present a promising strategy for the treatment of endometriosis. To ensure the efficacy of RNAi-based therapy, it is critical to develop carriers capable of precisely delivering small interfering RNA (siRNA) to target cells. Additionally, the instability of polyplexes in vivo must be regarded as a pivotal aspect influencing the success of non-viral delivery. In this study, we introduce ternary polyplexes comprising siRNA and a carrier derived from an arginine–histidine-rich peptide, which is further coated with a glutamate–histidine-rich polymer modified using an SDF-1 chemokine-derived ligand for targeting CXCR4-expressing cells. The physicochemical characteristics of the siRNA-polyplexes, along with cellular toxicity and GFP gene silencing efficacy, were assessed in vitro. The anti-angiogenic potential of anti-VEGFA siRNA-polyplexes was evaluated by measuring the size of endometrial lesions, conducting immunohistochemical staining, and analyzing VEGFA gene expression. For in vivo experiment, a rat model of endometriosis induced by subcutaneous auto-transplantation of uterine tissue was utilized. A significant reduction in the growth of endometriotic implants and silencing of VEGFA gene expression was observed when compared to the saline-treated control group. The results of this study strongly suggest that the developed ternary polyplexes have significant potential as an efficient tool for the development of anti-angiogenic RNAi-based therapies for endometriosis. Full article

Bradysia odoriphaga Yang et Zhang damages roots of 30 plant species, resulting in >50% yield loss. Heat stress can not only affect the survival but also affect the expression of heat shock proteins of B. odoriphaga. In this study, two small heat shock protein genes, Hsp21.9 and Hsp22.3, were cloned from B. odoriphaga. The full-length cDNA sequences of BoHsp21.9 and BoHsp22.3 were 749 and 941 bp in length and contained a 588 and 594 bp open reading frame (ORF), encoding a protein of 196 and 198 amino acids with a calculated molecular weight of 21.9 and 22.3 kDa and an isoelectric point of 6.84 and 6.91. Phylogenetic tree analysis showed that BoHsp21.9 and BoHsp22.3 clustered into one branch with flies. qRT-PCR analyses indicated that BoHsp21.9 and BoHsp22.3 were expressed in all tested developmental stages and body segments, especially induced by heat stress. RNAi-mediated silencing of BoHsp21.9 and BoHsp22.3 significantly decreased the survival rate of fourth-instar larvae when exposed to 38 °C. This is the first study on small heat shock proteins in B. odoriphaga, and BoHsp21.9, and BoHsp22.3 play important roles in the molecular mechanism of B. odoriphaga to theromotolerance. Full article

Pollution with heavy metals, such as cadmium (Cd), can significantly affect insect growth, development, and behavior. The midgut is an essential organ for stress response. Chitin synthase-2 (CHS-2) is closely associated with forming the peritrophic membrane (PM). The fourth-instar larvae of Aedes albopictus were exposed to varying concentrations of Cd. The results showed that Cd inhibited chitin synthesis and metabolism-related genes, but thickened the midgut PM, indicating that the larvae could respond to Cd stress through the midgut PM. Silencing CHS-2 by RNA interference resulted more severe vacuolization and malformation of midgut epithelial cells without midgut PM protection. Additionally, there was an intensified redox reaction, upregulated expression of metallothionein (MT) and heat shock proteins 70 (HSP70), and increased activity of antioxidant enzymes at some scattered time points. This study confirms that CHS-2 is involved in oxidative stress induced by Cd exposure by regulating PM formation. This study also contributes to further understanding the resistance mechanism of Ae. albopictus under Cd stress, thereby establishing a theoretical foundation for the future studies of them, which is concerned with the possibility of Ae. albopictus as a water environment detection and the control of Ae. albopictus based on resistance mechanism. Full article

Obesity causes millions of deaths each year due to metabolic complications, making it a major public health challenge. It results from a chronic imbalance between caloric intake and energy expenditure. Among central structures regulating energy balance, the dorsal vagal complex (DVC) integrates metabolic signals from energy stores and the gastrointestinal tract and coordinates autonomic responses. While historically overshadowed by a focus on neurons, the role of glial cells in regulating energy balance is now well established. Connexin 43 (Cx43) is a well-known protein expressed by astrocytes, playing a key role in glial and neuroglial communication. To investigate the role of astrocytic Cx43 within the DVC, where its expression is remarkably high, we specifically reduced it using an RNA interference approach. Although reduced Cx43 expression led to modified astrocyte and microglia morphology and phenotype, our analyses did not reveal significant changes in the animal’s metabolic phenotype under standard feeding conditions as well as under a high-fat, high-sugar diet. These results suggest that denser astrocytic tiling and hyper-ramified microglia may constitute a buffering system that preserves metabolic and autonomic outputs when a single connexin pathway fails. Full article

Cold stress reduces horticultural crop yield and postharvest quality by disrupting membrane fluidity, redox equilibrium, and the cell wall structure. This results in chilling injury, tissue softening, and loss of color. Long noncoding RNAs (lncRNAs) have emerged as key integrators of plant cold signaling pathways. LncRNAs mediate the interaction between calcium signaling systems and transcriptional cascades while coordinating hormone signaling networks, including those involving abscisic acid, jasmonic acid, ethylene, salicylic acid, and brassinosteroids. LncRNAs influence gene regulation through chromatin-based guidance, sequestration of repressive complexes, natural antisense transcriptional interference, microRNA-centered competing endogenous RNA networks, and control of RNA splicing, stability, localization, and translation. Studies in horticultural species revealed that cold-responsive lncRNAs regulate processes essential for fruit firmness, antioxidant levels, and shelf-life, including lipid modification, reactive oxygen species balance, and cell wall or cuticle remodeling. This review aims to summarize tissue- and developmental stage-specific expression patterns and highlight experimental approaches to validate RNA function, including gene editing, transcript recovery, advanced sequencing, and analysis of protein-RNA interactions. Integrating these results will facilitate the development of precise molecular markers and nodes of regulatory networks that increase cold tolerance, and improve the quality of horticultural crops. Full article

Vector-borne diseases account for 17% of all infectious diseases. The most effective strategies for controlling these diseases have focused on decreasing the vector population, primarily through the use of insecticides. Many insecticides have no specific targets, harming pollinators and beneficial insects. Additionally, the vector populations are developing resistance, reducing the effectiveness of these strategies and increasing ecological damage. Double-strand RNA (dsRNA) is widely used in insects to study gene function by knocking down their expression. Recently, this technology has been applied to develop RNAi-based insecticides for controlling agricultural pests. These biopesticides demonstrate high specificity, as insects do not develop resistance to them, and they cause minimal ecological damage. These pesticides knock down the expression of key genes related to vital functions, development, and reproduction, which affects the insect life cycle and consequently decreases their populations. This review focuses on using RNA interference (RNAi)-based insecticides for controlling major insect vectors, including mosquitoes, kissing bugs, and ticks. We examine the advancements and challenges associated with this technology, considering the complex life cycles and feeding behavior of these insects. Furthermore, we discuss gaps in knowledge about vector biology and delivery strategies for dsRNA, which need to be addressed to enhance the application and efficiency of this emerging technology for controlling vector-borne diseases. Full article

Childhood cancer is rare, with about 1 in 260 children developing cancer before age 20. However, it remains a leading cause of death for children and adolescents worldwide. The 5-year survival rate for childhood cancer in high-income countries exceeds 80%, but globally, the average survival rate is around 37%, highlighting significant disparities across the globe. Despite the life-saving impact of current treatment regimens, long-term side effects and risks are always concerns. Therefore, there is a continuing urgent need for novel therapies to overcome the limitations of existing approaches and improve patient outcomes. Targeted drug therapies that interfere with cancer-causing genes play a vital role in cancer treatment by specifically targeting cancer cells. TFs are primary drivers of gene expression that are critical in various pediatric cancers. Chromosomal rearrangements, involving changes in chromosome structure such as deletions, duplications, inversions, and translocations, can significantly alter TF activity and downstream gene expression. Dysregulation of TFs disrupts gene expression networks and has been strongly linked to the development and progression of many pediatric cancers, making them promising therapeutic targets. Several approaches targeting TFs, including small-molecule inhibitors designed to block TF-DNA binding, TF-cofactor interactions, or their epigenetic regulation, as well as RNA interference, have been developed. More recently, approaches like PROTACs (Proteolysis-Targeting Chimeras) and molecular glue degraders offer new therapeutic possibilities in pediatric cancers. These innovations represent a paradigm shift in pediatric oncology, offering hope for more targeted, less toxic treatment options. This review discusses the critical role of TFs in childhood cancers and emphasizes the need for evolving therapeutic strategies aimed at targeting these key regulators to improve outcomes for young patients. Full article

G protein-coupled receptors (GPCRs) are considered the largest and most variable family of transmembrane receptors regulating physiological processes such as toxicological responses and insecticide resistance development. The present study investigated the responses of Methuselah (Mth), belonging to GPCR family B in the Diamondback Moth (DBM), Plutella xylostella, to chlorantraniliprole (CAP). Genome-wide identification and phylogenetic analysis of Pxmth genes revealed their evolutionary relationships and functional classifications. Expression profiling demonstrated significant overexpression of Pxmth2 in the CAP-resistant strain. Additionally, the tertiary and secondary structures of Pxmth2 were characterized, providing insights into its functional role. Silencing Pxmth2 via RNA interference (RNAi) reduced resistance of DBM to CAP and suppressed downstream stress-associated genes (CYP6B6, CYP6B7, CYP6BF1), increasing susceptibility to the insecticide. The function of Pxmth2 was further explored using a transgenic line of Drosophila melanogaster engineered to overexpress the gene; flies overexpressing Pxmth2 exhibited a significantly increased resistance to CAP compared to controls. These findings indicate that Pxmth2 contributes to CAP resistance in DBM and highlights potential molecular targets for improving pest management strategies. Full article

Aphids are sap-sucking pests that cause substantial damage to fruit and fibre crops through direct feeding and transmission of plant viruses. While chemical pesticides remain the primary method of control, their use raises concerns related to human health, environmental contamination, pesticide resistance, and impacts on beneficial insects. As a sustainable alternative, spray-on double-stranded RNA (dsRNA) technology offers a promising approach to induce RNA interference (RNAi) in target pests. For RNAi to be effective against sap-sucking insects like the green peach aphid (Myzus persicae), it is essential to identify genes whose silencing disrupts vital physiological functions. In this study, artificial diet (AD)-based feeding assays were used to evaluate dsRNAs targeting eight genes involved in neural function, osmoregulation, feeding behaviour, and nucleic acid/protein metabolism. dsRNAs were administered individually, in combinations, or as a multi-target stacked construct. After 98 h of feeding, aphid mortality ranged from 14 to 72% (individual targets), 78–85% (combinations), and 54% (stacked construct). Transcript knockdown varied from 6.3% to ~54%, though a consistent correlation with mortality was not always observed. The gene targets and combinatorial dsRNA strategies identified in this study provide a foundation for developing RNAi-based crop protection technologies against M. persicae infestation. Full article