Search Results (8,781)

In the context of global warming, heat tolerance is becoming a crucial physiological trait influencing fish species’ distribution and survival. While our understanding of fish heat tolerance and stress has expanded from behavioral studies to transcriptomic analyses, knowledge at the transcriptomic level is still limited. Recently, the highly conserved microRNAs (miRNAs) have provided new insights into the molecular mechanisms of heat stress in fish. This review systematically examines current research across three main reference databases to elucidate the universal responses and mechanisms of fish miRNAs under heat stress. Our initial screening of 569 articles identified 13 target papers for comprehensive analysis. Among these, at least 214 differentially expressed miRNAs (DEMs) were found, with 15 DEMs appearing in at least two studies (12 were upregulated and 13 were downregulated). The 15 recurrent DEMs were analyzed using DIANA mirPath v.3 and the microT-CDS v5.0 database to identify potential target genes. The results suggest that multiple miRNAs target various genes, forming a complex network that regulates glucose and energy metabolism, maintains homeostasis, and modulates inflammation and immune responses. Significantly, miR-1, miR-122, let-7a, and miR-30b were consistently differentially expressed in multiple studies, indicating their potential relevance in heat stress responses. However, these miRNAs should not be considered definitive biomarkers without further validation. Future research should focus on experimentally confirming their regulatory roles through functional assays, conducting transcriptomic comparisons across different species, and performing target validation studies. These miRNAs, conserved across species, could be valuable for monitoring wild fish health, enhancing aquaculture breeding, and guiding conservation strategies. However, the specific regulatory mechanisms of these miRNAs need clarification to confirm their reliability as biomarkers for thermal stress. Full article

Pineoblastoma (PB) is a rare yet lethal pediatric brain cancer of the pineal gland, a small endocrine organ that secretes melatonin to regulate the circadian rhythm. For PB patients ≤5 years of age, the overall survival rate is approximately 15%; metastatic PB is incurable. Standard treatment, including surgical resection, radiation, and systemic chemotherapy, improves survival but compromises neurocognitive function. A better understanding of the disease and the generation of preclinical models may enable re-evaluation of previous clinical trials, development of precision therapeutic strategies and improve patient outcome. Over the past 5 years, PB has been recognized to include several major subtypes driven by (i) loss of microRNA processing factors DICER and DROSHA characterized by a relatively good prognosis; (ii) loss of the retinoblastoma tumor suppressor RB1; and (iii) amplification or induction of the cMYC protooncogene, with the latter two subtypes exhibiting exceedingly poor prognosis. Recently, mouse models for the major PB subtypes (RB1-, DICER1- and DROSHA-) except MYC- have been established. This progress, including better understanding of the disease, cell of origin, tumor progression, role of autophagy, and targetable vulnerabilities, holds promise for novel therapeutic strategies to combat each subtype of this lethal childhood malignancy. Full article

Background: In recent years, micro ribonucleic acids (miRNAs) have been recognized as key regulators in numerous biological processes, particularly in the development and progression of diseases. As a result, extensive research has focused on uncovering the critical involvement of miRNAs in disease mechanisms to better comprehend the underlying causes of human diseases. Despite these efforts, relying solely on biological experiments to identify miRNA-disease associations is both time-consuming and costly, making it an impractical approach for large-scale studies. Methods: In this paper, we propose a novel DeepWalk-based graph embedding method for predicting miRNA–disease association (DWMDA). Using DeepWalk, we extracted meaningful low-dimensional vectors from the miRNA and disease networks. Then, we applied a deep neural network to identify miRNA–disease associations using the low-dimensional vectors of miRNAs and diseases extracted via DeepWalk. Results: An ablation study was conducted to assess the proposed graph embedding modules. Furthermore, DWMDA demonstrates exceptional performance in two major cancer case studies (breast and lung), with results based on statistically robust measures, further emphasizing its reliability as a method for identifying associations between miRNAs and diseases. Conclusions: We expect that our model will not only facilitate the accurate prediction of disease-associated miRNAs but also serve as a generalizable framework for exploring interactions among various biological entities. Full article

Cryptosporidium, a protozoan parasite affecting the gastrointestinal system, is primarily known for causing diarrhea, especially in those with weakened immune systems. However, there is increasingly persuasive evidence that it may be directly involved in tumorigenesis. This review examines some of the potential mechanisms through which Cryptosporidium infections can induce cancer, specifically chronic inflammation, manipulation of the immune system, and alteration of cell signaling pathways. Persistent inflammation with immune system changes due to chronic infection, particularly among immunocompromised hosts, leads to a microenvironment that facilitates tumorigenesis. Cryptosporidium manipulates important cellular pathways such as PI3K, NF-κB, Wnt, and p38/MAPK to promote cell survival, regulate immune responses, and foster tissue remodeling, all of which contribute to a tumor-friendly microenvironment. Moreover, Cryptosporidium virulence factors such as ROP1, sPLA2, and microRNAs disrupt host cellular stability and significantly alter host cellular gene expression, which also exacerbates inflammation and tissue damage. Epidemiological data have indicated higher rates of Cryptosporidium infection in cancer patients, especially patients with gastrointestinal cancers. This, among other observations, raises the possibility that the infection may be connected to cancer progression. In animal models, especially studies with C. parvum-challenged rodents, chronic inflammation, immune repression, and genetic mutations related to neoplasia have been reported. While this has provided us with valuable information, we still have a long way to go to fully understand the long-term ramifications of Cryptosporidium infection. These cover aspects such as the contribution of latent infections and the genetic diversity of Cryptosporidium strains in cancer. Further investigation is urgently needed to understand the molecular processes by which Cryptosporidium might contribute to carcinogenesis and explore potential strategies for therapy and prevention especially among immunocompromised populations. Full article

Background/Objectives: Blood is an essential component of the immune system. As post-transcriptional regulators, miRNAs, abundant in blood, are necessary aspects in blood’s immune and physiological functions. However, there is limited knowledge about the expression and function of miRNAs in the blood of giant pandas. Methods: We comparatively analyzed miRNA expression profiles in the blood of giant pandas of different ages using small-RNA sequencing technology. Results: We identified 393 known miRNAs, 219 conserved miRNAs, and 71 novel miRNAs in the blood of giant pandas, and functional enrichment analysis showed that the genes regulated by DE (differentially expressed) miRNAs were mainly enriched in the regulation of enzyme-linked receptor protein signaling pathways and the signaling pathways of MAPK, Hippo, and FoXO. Conclusions: Our study clarified giant pandas’ blood miRNA expression profiles at different developmental stages, which will help elucidate the blood immunity and regulation of blood cell physiological functions in giant pandas. Full article

Growing evidence demonstrates the critical roles of long non-coding RNAs (lncRNAs) in osteoarthritis (OA) pathogenesis. The lncRNA XIST is one of the most commonly studied; however, its function remains unclear. This study aimed to research the molecular mechanism of XIST in human OA chondrocytes. Cells were transfected with small interfering RNA against XIST or with a microRNA (miR)-146a inhibitor in the presence of interleukin (IL)-1β. Viability was detected using MTT; apoptosis using cytometry; and XIST, miR-146a, B-cell lymphoma (BCL)2, and metalloproteinase (MMP)-13 expression using real-time PCR. The analysis of p50 and p65 nuclear factor (NF)-κB was conducted using PCR and immunofluorescence. Our findings showed that XIST was highly expressed in OA chondrocytes when compared to T/C-28a2 lines. Furthermore, XIST silencing significantly promoted survival and limited apoptosis, with a concomitant over expression of BCL2, reduction in MMP-13 mRNA, and NF-κB activation after IL-1β stimulus. Conversely, miR-146a was significantly down-regulated in OA cells, while its levels were increased following XIST silencing; moreover, miR-146a inhibition induced opposite results to those caused by XIST. Finally, the down-regulation of XIST was correlated to the over-expression of miR-146a, with a consequent modulation of BCL2, MMP-13, and NF-κB. This study suggests an influence of the XIST/miR-146a axis on the viability, apoptosis, and matrix degradation occurring in OA. Full article

Molecular biomarker profiling is an emerging field in maternal-fetal health with the potential to transform early detection and prediction of placental dysfunction. By analysing a range of biomarkers in maternal blood, researchers and clinicians can gain crucial insights into placental health, enabling timely interventions to enhance fetal and maternal outcomes. Placental structural function is vital for fetal growth and development, and disruptions can lead to serious pregnancy complications like preeclampsia. While conventional methods such as ultrasound and Doppler velocimetry offer valuable information on fetal growth and blood flow, they have limitations in predicting placental dysfunction before clinical signs manifest. In contrast, molecular biomarker profiling can provide a more comprehensive assessment by measuring proteins, metabolites, and microRNAs (miRNAs) in maternal blood, reflecting the placenta’s endocrine and metabolic functions. This approach offers a deeper understanding of placental health and function, aiding in early detection and prediction of complications. Challenges in developing molecular biomarker profiling include pinpointing specific molecular changes in the placenta linked to pathologies, timing predictions of conditions before clinical onset, and understanding how placental dysfunction affects maternal metabolism. Validating specific biomarkers and integrating them effectively into clinical practice requires further research. This review underscores the significance of molecular biomarker profiling as a powerful tool for early detection and prediction of placental dysfunction in maternal-fetal health. Through an exploration of biomarker analysis, we delve into how a deeper understanding of placental health can potentially improve outcomes for both mother and baby. Furthermore, we address the critical need to validate the utility of biomarkers and effectively integrate them into clinical practice. Full article

Plants are constantly exposed to abiotic and biotic stresses that seriously affect crop yield and quality. A coordinated regulation of plant responses to combined abiotic/biotic stresses requires crosstalk between signaling pathways initiated by each stressor. Interconnected signaling pathways further finetune plant stress responses and allow the plant to respond to such stresses effectively. The plant nutritional status might influence disease resistance by strengthening or weakening plant immune responses, as well as through modulation of the pathogenicity program in the pathogen. Here, we discuss advances in our understanding of interactions between nutrient stress, deficiency or excess, and immune signaling pathways in the context of current agricultural practices. The introduction of chemical fertilizers and pesticides was a major component of the Green Revolution initiated in the 1960s that greatly boosted crop production. However, the massive application of agrochemicals also has adverse consequences on the environment and animal/human health. Therefore, an in-depth understanding of the connections between stress caused by overfertilization (or low bioavailability of nutrients) and immune responses is a timely and novel field of research with important implications for disease control in crop species. Optimizing nutrient management practices tailored to specific environmental conditions will be crucial in maximizing crop production using environmentally friendly systems. Full article

Fine particulate matter (PM_2.5) is often linked to a range of respiratory diseases and cellular damage. Although studies have shown that the expression profiles of microRNAs (miRNAs) are altered during lung damage brought on by PM_2.5, the underlying functions of miRNAs remain poorly understood. In this research, we explored the role of PM_2.5-induced apoptosis in detail and focused on the miRNA (miR-212-5p) that regulates apoptosis. Through a dual-luciferase assay, a direct targeting connection between laminin subunits γ2 (LAMC2) and α3 (LAMA3) and miR-212-5p was successfully demonstrated. This study focused on revealing the negative regulatory relationship between miR-212-5p and LAMC2 and LAMA3, providing important clues for a deeper understanding of the relevant physiological and pathological mechanisms. The present study showed that LAMC2 and LAMA3 positively regulate the PI3K-AKT pathway and negatively regulate the NF-κB pathway, which directly leads to significant changes in apoptosis rates. This study reveals a previously unrecognized molecular mechanism by showing that miR-212-5p directly targets LAMC2 and LAMA3 and thus associates with PM_2.5-induced apoptosis via the PI3K/AKT/NF-κB pathway. These findings not only redefine the role of miR-212-5p in apoptosis but also open up new avenues for future research. Full article

Breast cancer is a highly heterogeneous disease; hence, it is crucial to understand its biology and identify new targets for the development of effective treatments. Galectin-1 is known to play an oncogenic role in breast cancer progression. It is known that oncogenic factors can influence cancer progression through interactions with miRNAs. The purpose of this study is to identify the clinical significance and biological role of galectin-1 and miR-22-3p in cancer progression according to the molecular subtype of breast cancer. We analyzed the expression of galectin-1 and miR-22-3p using cancer tissues and the correlation with clinical pathological characteristics. In addition, we investigated the regulation of the cell cycle and EMT processes of cancer progression through the galectin-1/miR-22-3p axis using cell lines of different breast cancer subtypes. miR-22-3p negatively regulates galectin-1 expression and the two molecules have opposite patterns of oncogenic and tumor-suppressive functions, respectively; furthermore, these two molecules are associated with metastasis-free survival. Cell experiments showed that miR-22-3p overexpression and galectin-1 knockdown inhibited the proliferation and invasion of breast cancer cells. Galectin-1 regulates different cancer progression pathways depending on the molecular subtype. In hormone receptor-positive breast cancer cells, galectin-1 knockdown mainly inhibited cell cycle-related substances and induced G0/G1 arrest, whereas in triple-negative breast cancer cells, it suppressed molecules related to the epithelial–mesenchymal transition pathway. In conclusion, the miR-22-3p/galectin-1 axis regulates different cancer metastasis mechanisms depending on the specific molecular subtype of breast cancer, and miR-22-3p/galectin-1 axis modulation may be a novel target for molecular subtype-specific personalized treatment. Full article

Background: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, yet fundamental studies regarding epigenetic regulation of ICAS are lacking. We hypothesized that, due to anatomical and/or functional differences, extracranial atherosclerosis is distinct from ICAS, which may explain the clinical variability as well. Methods: We chose a number of miRNAs involved in various steps of atherogenesis (namely, miR-712/205-5p/-3p, miR-106b-3p/-5p, miR-146a-3p/-5p, miR-100-3p/miR-5p, miR-200c-3p/-5p, miR-532-3p/-5p, and miR-126-3p/-5p) and examined their plasma levels in a cohort of patients with carotid stenosis > 50% (n = 35, mean age: 65 years, 54% male; 12 patients had ICAS). Results: A differential pattern of circulating miR expression was found in ICAS patients: there was an overexpression of miR-712/205-5p, miR-106b-5p, miR-146a-5p, miR-200c-5p, miR-532-3p, and miR-126-3p. The following miRs were underexpressed in intracranial atherosclerosis—miR-712/205-3p and miR-100-3p. These changes represent a plethora of atherogenic mechanisms: smooth muscle cell migration (miR-712/205, miR-532), foam cell formation (miR-106b, miR-146a), endothelial dysfunction (miR-200c), low-density lipoprotein-induced vascular damage (miR-100), and leukocyte recruitment (miR-126). In symptomatic ICAS patients, we observed a statistically significant upregulation of miR-712/205-3p and miR-146a-5p. Conclusions: Overall, the findings of our pilot study revealed several new and interesting associations: (1) intracranial atherosclerosis seems to have a different epigenetic profile (regarding circulating microRNA expression) than isolated extracranial vessel involvement; (2) ischemic stroke in ICAS may be potentiated by other pathophysiologic mechanisms than in extracranial-only atherosclerosis (ECAS). Certain miRs (e.g., miR-712/205) seem to have a larger impact on ICAS than on extracranial atherosclerosis; this may be potentially linked to difference between extra- and intracranial artery morphology and physiology, and/or may lead to the said differences. This underscores the importance of making a distinction in future epigenetic studies between ECAS and ICAS, as the mechanisms of atherogenesis are likely to vary. Full article

Over 400 articles on the pathophysiology of brain aging, neuroaging, and neurodegeneration were reviewed, with a focus on epigenetic mechanisms and numerous non-coding RNAs. In particular, this review the accent is on microRNAs, the discovery of whose pivotal role in gene regulation was recognized by the 2024 Nobel Prize in Physiology or Medicine. Aging is not a gradual process that can be easily modeled and described. Instead, multiple temporal processes occur during aging, and they can lead to mosaic changes that are not uniform in pace. The rate of change depends on a combination of external and internal factors and can be boosted in accelerated aging. The rate can decrease in decelerated aging due to individual structural and functional reserves created by cognitive, physical training, or pharmacological interventions. Neuroaging can be caused by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle, and environmental factors, which are especially noticeable in space environments where adaptive changes can trigger aging-like processes. Numerous candidate molecular biomarkers specific to neuroaging need to be validated to develop diagnostics and countermeasures. Full article

Colorectal cancer (CRC) continues to be a primary contributor to the global health burden, and early detection is vital for optimal outcomes. Standard detection techniques, including colonoscopy and fecal occult blood tests, have been confirmed effective yet their invasiveness and poor sensitivity are a limitation. MicroRNA (miRNA) are now recognized as stable non-invasive biomarkers with differential expression in cancerous tissues, but reports have been heterogeneous and studied under different settings. This study, completed based on PRISMA guidelines, was a systematic review of miRNA signature diagnostic accuracy to detect early CRC. Case-case control studies, cross-sectional, and cohort research published between 2014–2024 were identified through the Scopus, PubMed, and Cochrane databases. We extracted diagnostic metrics such as sensitivity and specificity while assessing bias with the ROBINS-e tool and the Newcastle-Ottawa Scale. Meta-analyses showed that miRNA panels have high diagnostic accuracy with a pooled sensitivity of 1.84 (95% CI: 1.48–2.19) and a pooled specificity of 1.43 (95% CI: 1.01–1.85). The accuracy of miRNA-139-3p was the highest among all panels. Meta-regression did not reveal any significant confounders, while publication bias was not detected. These results highlight the miRNA panels’ potential as non-invasive biomarkers in early CRC detection, providing a promising alternative to conventional screening methods, with miRNA-139-3p as the most diagnostically accurate biomarker. Full article

Lung cancer exhibits substantial inter- and intra-tumor heterogeneity, with features that present significant challenges in advancing biomarker discovery and the development of targeted therapeutics. To fill this gap, we employed single-cell RNA sequencing (scRNA-seq) and advanced bioinformatics tools to evaluate the transcriptomic heterogeneity of immortalized, non-transformed (BEAS2B) and transformed (H460) lung epithelial cell lines and their responses to carcinogen challenge. Gene expression profiles resolved four primary clusters further discretized into unique subclusters based on genetic signatures and phenotypic profiles. Profiles of long non-coding RNAs (lncRNAs) identified microRNA host genes, antisense RNA genes, divergent transcript, and long intergenic non-coding RNAs as contributors to cellular heterogeneity. These findings indicate that distinct patterns of gene expression, remarkably in lncRNAs, define cellular heterogeneity in non-transformed versus transformed cells. These features can be exploited for the development of therapies directed at specific cell subpopulations in precancerous lesions and within lung tumors. Full article

The intersection of COVID-19 and cardiovascular disease (CVD) has emerged as a significant area of research, particularly in understanding the impact of antiplatelet therapies like ticagrelor and clopidogrel. COVID-19 has been associated with acute cardiovascular complications, including myocardial infarction, thrombosis, and heart failure, exacerbated by the virus’s ability to trigger widespread inflammation and endothelial dysfunction. MicroRNAs (miRNAs) play a critical role in regulating these processes by modulating the gene expressions involved in platelet function, inflammation, and vascular homeostasis. This study explores the potential of miRNAs such as miR-223 and miR-126 as biomarkers for predicting resistance or responsiveness to antiplatelet therapies in COVID-19 patients with cardiovascular disease. Identifying miRNA signatures linked to drug efficacy could optimize treatment strategies for patients at high risk of thrombotic events during COVID-19 infection. Moreover, understanding miRNA-mediated pathways offers new insights into how SARS-CoV-2 exacerbates CVD, particularly through mechanisms like cytokine storms and endothelial damage. The findings of this research could lead to personalized therapeutic approaches, improving patient outcomes and reducing mortality in COVID-19-associated cardiovascular events. With global implications, this study addresses the urgent need for effective management of CVD in the context of COVID-19, focusing on the integration of molecular biomarkers to enhance the precision of antiplatelet therapy. Full article