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Toxics May 2024It is well known that Particulate Matter2.5 (PM) has a major adverse effect on the organism. However, the health hazards of livestock farm PM to humans and animals are...
It is well known that Particulate Matter2.5 (PM) has a major adverse effect on the organism. However, the health hazards of livestock farm PM to humans and animals are not yet known, and the role of miRNAs in the cellular damage induced by livestock farm PM is also unclear. Therefore, our study used cowshed PM to stimulate rat alveolar macrophage NR8383 to construct an in vitro injury model to investigate the effect of miR-122-5p on PM-induced apoptosis in the NR8383. The level of apoptosis was quantified by flow cytometry and Hoechst 33342/PI double staining. Furthermore, the potential target gene Collagen type IV alpha () of miR-122-5p was identified through the use of bioinformatics methods. The results demonstrated a decline in cell viability and an increase in apoptosis with rising PM concentrations and exposure durations. The transfection of miR-122-5p mimics resulted in an upregulation of the pro-apoptotic protein Bcl-xL/Bcl-2 and activation of cleaved caspase-3 while inhibiting the anti-apoptotic protein B-cell lymphoma-2. The experimental data indicate that miR-122-5p is involved in the apoptotic process by targeting . Furthermore, the overexpression of was observed to enhance the PM-activated PI3K/AKT/NF-κB signaling pathway, which contributed to the inhibition of apoptosis. This finding offers a promising avenue for the development of therapeutic strategies aimed at mitigating cellular damage induced by PM exposure.
PubMed: 38922066
DOI: 10.3390/toxics12060386 -
Non-coding RNA May 2024Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments,...
Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds which modify microRNAs' (small, expression-regulating molecules) expression. In this study, we investigated the antihypertensive properties of Chios mastic through the assessment of miR-21 levels. Herein, plasma samples of 57 individuals with hypertension, recruited for the purposes of the HYPER-MASTIC study, were analyzed. This was a clinical trial with Chios mastic supplements in which the patients were divided into groups receiving high and low mastic doses and placebo supplements, respectively. miR-21 was significantly upregulated in patients compared to normotensive individuals. Mean changes in miR-21 levels were statistically significant, after adjusting for sex and age, between the placebo and low-dose group and between the low- and high-dose group. Post-intervention miR-21 levels were positively associated with night-time systolic blood pressure, pulse pressure, and central systolic mean arterial pressure and negatively associated with night-time pulse wave velocity in the low-dose group. Our findings suggest a potential implication of miR-21 in the association of Chios mastic with night-time blood pressure measurements.
PubMed: 38921830
DOI: 10.3390/ncrna10030033 -
Pathogens (Basel, Switzerland) Jun 2024In the original publication [...].
In the original publication [...].
PubMed: 38921820
DOI: 10.3390/pathogens13060502 -
Insects Jun 2024The investigation of genetics-based biopesticides has become a central focus in pesticide studies due to their inherent advantages, including species specificity,...
The investigation of genetics-based biopesticides has become a central focus in pesticide studies due to their inherent advantages, including species specificity, environmental safety, and a wide range of target genes. In this study, a mixture of miR-184 agomir and nanomaterial star polycation (SPc) was used to treat the nymphs of the English grain aphid, (F.). The life parameters of the aphids at various developmental stages were analyzed using an age-stage two-sex life table to assess the effect of miR-184 agomir on the experimental population. The results indicated that miR-184 agomir had a significant negative effect on four key life parameters, including the intrinsic rate of increase, the finite rate of increase, the net rate of increase, and the mean generation time. The population prediction revealed a substantial reduction (91.81% and 95.88%) in the population size of at 60 d after treatment with miR-184 agomir, compared to the control groups. Our findings suggest that the miR-184 agomir has the potential to reduce the survival rate and mean longevity of , highlighting its potential as a promising candidate for the development of an effective genetics-based biopesticide.
PubMed: 38921173
DOI: 10.3390/insects15060459 -
Insects Jun 2024iGABAR, a member of the Cys-loop ligand-gated ion channel superfamily, is a significant target of the insecticide ivermectin (IVM). GRD is the potential subunit of the...
iGABAR, a member of the Cys-loop ligand-gated ion channel superfamily, is a significant target of the insecticide ivermectin (IVM). GRD is the potential subunit of the insect iGABAR. However, little information about GRD in has been reported. In this study, we involved cloning and characterizing the iGABAR subunit of (). Sequence analysis indicated that , as part of the cysteine-loop ligand-gated ion channel family, is similar to other insect . RNA interference (RNAi) was employed to explore IVM resistance in , resulting in a significant reduction in expression ( < 0.05), and the mortality of adults with knockdown was significantly decreased after exposure to ivermectin. Bioinformatics prediction identified miR-71-5p as a potential regulator of . In vitro, dual-luciferase reporter assays confirmed that expression was regulated by miR-71-5p. Microinjection of miR-71-5p mimics upregulated miR-71-5p expression and downregulated gene expression, reducing mortality by 34.52% following IVM treatment. Conversely, microinjection of a miR-71-5p inhibitor decreased miR-71-5p expression but did not affect the susceptibility to IVM despite increased expression ( < 0.05). In conclusion, , as one of the iGABA receptor subunits, is a potential target of ivermectin. It may influence ivermectin resistance by modulating the GABA signaling pathway. The inhibition of expression by miR-71-5p decreased ivermectin resistance and consequently lowered the mortality rate of mosquitoes. This finding provides empirical evidence of the relationship between and its miRNA in modulating insecticide resistance, offering novel perspectives for mosquito control strategies.
PubMed: 38921167
DOI: 10.3390/insects15060453 -
Current Issues in Molecular Biology May 2024Alzheimer's disease (AD) is the world's most common neurodegenerative disease, expected to affect up to one-third of the elderly population in the near future. Among the... (Review)
Review
Alzheimer's disease (AD) is the world's most common neurodegenerative disease, expected to affect up to one-third of the elderly population in the near future. Among the major challenges in combating AD are the inability to reverse the damage caused by the disease, expensive diagnostic tools, and the lack of specific markers for the early detection of AD. This paper highlights promising research directions for molecular markers in AD diagnosis, including the diagnostic potential of microRNAs. The latest molecular methods for diagnosing AD are discussed, with particular emphasis on diagnostic techniques prior to the appearance of full AD symptoms and markers detectable in human body fluids. A collection of recent studies demonstrates the promising potential of molecular methods in AD diagnosis, using miRNAs as biomarkers. Up- or downregulation in neurodegenerative diseases may not only provide a new diagnostic tool but also serve as a marker for differentiating neurodegenerative diseases. However, further research in this direction is needed.
PubMed: 38920976
DOI: 10.3390/cimb46060304 -
Dentistry Journal May 2024During the last few decades there has been a growing interest in understanding the involvement of epigenetics in the pathogenesis and treatment of periodontal disease.... (Review)
Review
During the last few decades there has been a growing interest in understanding the involvement of epigenetics in the pathogenesis and treatment of periodontal disease. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), may serve as epigenetic modifiers affecting the expression of genes involved in the pathogenesis of inflammatory and autoimmune diseases. There is increasing evidence supporting the idea that the function of all three types of ncRNAs seems to be interdependent. LncRNAs can act as miRNA decoys, while circRNAs can act as miRNA sponges, leading to the re-expression of miRNA target genes. The purpose of this review is to evaluate the expression patterns of ncRNAs in periodontal disease. Studies demonstrate a positive correlation between miRNA expression and periodontitis; however, this cannot be claimed for lncRNAs and circRNAs, which appear to be differentially expressed in periodontitis patients. Several studies have also suggested utilizing ncRNAs as diagnostic and prognostic biomarkers in periodontitis, or even as potential therapeutic targets; Nevetheless, the evidence to support this is premature. Future well-designed research remains necessary to establish the functional role of ncRNAs in the evolution and progression of periodontal disease.
PubMed: 38920860
DOI: 10.3390/dj12060159 -
Cells Jun 2024Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms... (Review)
Review
Neurological and neuropsychiatric disorders pose substantial challenges to public health, necessitating a comprehensive understanding of the molecular mechanisms underlying their pathogenesis. In recent years, the focus has shifted toward the intricate world of non-coding RNAs (ncRNAs), a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. This review explores the emerging significance of ncRNAs in the context of neurological and neuropsychiatric disorders, shedding light on their diverse functions and regulatory mechanisms. The dysregulation of various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), has been implicated in the pathophysiology of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and mood disorders. This review delves into the specific roles these ncRNAs play in modulating key cellular processes, including synaptic plasticity, neuroinflammation, and apoptosis, providing a nuanced understanding of their impact on disease progression. Furthermore, it discusses the potential diagnostic and therapeutic implications of targeting ncRNAs in neurological and neuropsychiatric disorders. The identification of specific ncRNA signatures holds promise for the development of novel biomarkers for early disease detection, while the manipulation of ncRNA expression offers innovative therapeutic avenues. Challenges and future directions in the field are also considered, highlighting the need for continued research to unravel the complexities of ncRNA-mediated regulatory networks in the context of neurological and neuropsychiatric disorders. This review aims to provide a comprehensive overview of the current state of knowledge and stimulate further exploration into the fascinating realm of ncRNAs in the brain's intricate landscape.
Topics: Humans; RNA, Untranslated; Nervous System Diseases; Mental Disorders; RNA, Circular; Animals; RNA, Long Noncoding; Gene Expression Regulation; MicroRNAs
PubMed: 38920691
DOI: 10.3390/cells13121063 -
Cells Jun 2024Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important...
Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.
Topics: Trabecular Meshwork; Humans; MicroRNAs; Glaucoma, Open-Angle; Transforming Growth Factor beta2; Transforming Growth Factor beta; Transforming Growth Factor beta1; Cells, Cultured; Gene Expression Regulation; Intraocular Pressure
PubMed: 38920689
DOI: 10.3390/cells13121060 -
Cells Jun 2024Non-coding RNAs (ncRNAs) have emerged as pivotal regulators in cellular biology, dispelling their former perception as 'junk transcripts'. Notably, the DLK1-DIO3 region...
Non-coding RNAs (ncRNAs) have emerged as pivotal regulators in cellular biology, dispelling their former perception as 'junk transcripts'. Notably, the DLK1-DIO3 region harbors numerous ncRNAs, including long non-coding RNAs (lncRNAs) and over 50 microRNA genes. While papillary thyroid cancer showcases a pervasive decrease in DLK1-DIO3-derived ncRNA expression, the precise mechanisms driving this alteration remain elusive. We hypothesized that epigenetic alterations underlie shifts in ncRNA expression during thyroid cancer initiation and progression. This study aimed to elucidate the epigenetic mechanisms governing DLK1-DIO3 region expression in this malignancy. We have combined the analysis of DNA methylation by bisulfite sequencing together with that of histone modifications through ChIP-qPCR to gain insights into the epigenetic contribution to thyroid cancer in cell lines representing malignancies with different genetic backgrounds. Our findings characterize the region's epigenetic signature in thyroid cancer, uncovering distinctive DNA methylation patterns, particularly within CpG islands on the lncRNA MEG3-DMR, which potentially account for its downregulation in tumors. Pharmacological intervention targeting DNA methylation combined with histone deacetylation restored ncRNA expression. These results contribute to the understanding of the epigenetic mechanisms controlling the DLK1-DIO3 region in thyroid cancer, highlighting the combined role of DNA methylation and histone marks in regulating the locus' expression.
Topics: Humans; Epigenesis, Genetic; DNA Methylation; Thyroid Neoplasms; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Calcium-Binding Proteins; Iodide Peroxidase; RNA, Long Noncoding; CpG Islands; Intercellular Signaling Peptides and Proteins; Histones; Membrane Proteins
PubMed: 38920632
DOI: 10.3390/cells13121001