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Nutrients May 2024Metabolic dysfunction-associated steatotic liver disease (MASLD), with a prevalence of 30% of adults globally, is considered a multifactorial disease. There is a lack of...
Multipanel Approach including miRNAs, Inflammatory Markers, and Depressive Symptoms for Metabolic Dysfunction-Associated Steatotic Liver Disease Diagnosis during 2-Year Nutritional Intervention.
Metabolic dysfunction-associated steatotic liver disease (MASLD), with a prevalence of 30% of adults globally, is considered a multifactorial disease. There is a lack of effective non-invasive methods for accurate diagnosis and monitoring. Therefore, this study aimed to explore associations between changes in circulating miRNA levels, inflammatory markers, and depressive symptoms with hepatic variables in MASLD subjects and their combined potential to predict the disease after following a dietary intervention. Biochemical markers, body composition, circulating miRNAs and hepatic and psychological status of 55 subjects with MASLD with obesity and overweight from the FLiO study were evaluated by undergoing a 6-, 12- and 24-month nutritional intervention. The highest accuracy values of combined panels to predict the disease were identified after 24 months. A combination panel that included changes in liver stiffness, high-density lipoprotein cholesterol (HDL-c), body mass index (BMI), depressive symptoms, and triglycerides (TG) yielded an AUC of 0.90. Another panel that included changes in hepatic fat content, total cholesterol (TC), miR15b-3p, TG, and depressive symptoms revealed an AUC of 0.89. These findings identify non-invasive biomarker panels including circulating miRNAs, inflammatory markers, depressive symptoms and other metabolic variables for predicting MASLD presence and emphasize the importance of precision nutrition in MASLD management and the sustained adherence to healthy lifestyle patterns.
Topics: Humans; Male; Female; Biomarkers; Depression; Middle Aged; MicroRNAs; Adult; Body Mass Index; Obesity; Inflammation; Triglycerides; Non-alcoholic Fatty Liver Disease; Liver; Fatty Liver
PubMed: 38892481
DOI: 10.3390/nu16111547 -
International Journal of Molecular... Jun 2024Globally, osteoporosis is the most common systemic skeletal disease. There are many factors that influence osteoporosis' development and progression. During the... (Review)
Review
Globally, osteoporosis is the most common systemic skeletal disease. There are many factors that influence osteoporosis' development and progression. During the pathogenesis of this disease, bone turnover is imbalanced between resorption and the formation of bone tissue. A growing interest has been devoted to the role that microRNA (miRNA) plays in osteoporosis regulation. A microRNA (miRNA) is a group of small single-stranded RNA molecules involved in regulating gene expression in eukaryotic organisms. As microRNAs (miRNAs) are key regulators of gene expression and can modulate processes related to bone metabolism, they have become increasingly important for studying osteoporosis pathogenesis. The available research suggests that miRNAs play an important role in regulating processes associated with bone metabolism, especially by influencing bone resorption and synthesis. Furthermore, microRNAs can also serve as potential therapeutic targets for osteoporosis, besides being a rapid and specific biomarker.
Topics: Osteoporosis; MicroRNAs; Humans; Animals; Gene Expression Regulation; Biomarkers; Bone and Bones; Bone Resorption
PubMed: 38892426
DOI: 10.3390/ijms25116240 -
International Journal of Molecular... Jun 2024(, Sg) is one of the early colonizing, supragingival commensal bacterium normally associated with oral health in human dental plaque. MicroRNAs (miRNAs) play an...
(, Sg) is one of the early colonizing, supragingival commensal bacterium normally associated with oral health in human dental plaque. MicroRNAs (miRNAs) play an important role in the inflammation-mediated pathways and are involved in periodontal disease (PD) pathogenesis. PD is a polymicrobial dysbiotic immune-inflammatory disease initiated by microbes in the gingival sulcus/pockets. The objective of this study is to determine the global miRNA expression kinetics in DL1-infected C57BL/6J mice. All mice were randomly divided into four groups ( = 10 mice/group; 5 males and 5 females). Bacterial infection was performed in mice at 8 weeks and 16 weeks, mice were euthanized, and tissues harvested for analysis. We analyzed differentially expressed (DE) miRNAs in the mandibles of -infected mice. Gingival colonization/infection by and alveolar bone resorption (ABR) was confirmed. All the -infected mice at two specific time points showed bacterial colonization (100%) in the gingival surface, and a significant increase in mandible and maxilla ABR ( < 0.0001). miRNA profiling revealed 191 upregulated miRNAs (miR-375, miR-34b-5p) and 22 downregulated miRNAs (miR-133, miR-1224) in the mandibles of -infected mice at the 8-week mark. Conversely, at 16 weeks post-infection, 10 miRNAs (miR-1902, miR-203) were upregulated and 32 miRNAs (miR-1937c, miR-720) were downregulated. Two miRNAs, miR-210 and miR-423-5p, were commonly upregulated, and miR-2135 and miR-145 were commonly downregulated in both 8- and 16-week-infected mice mandibles. Furthermore, we employed five machine learning (ML) algorithms to assess how the number of miRNA copies correlates with infections in mice. In the ML analyses, miR-22 and miR-30c (8-week), miR-720 and miR-339-5p (16-week), and miR-720, miR-22, and miR-339-5p (combined 8- and 16-week) emerged as the most influential miRNAs.
Topics: MicroRNAs; Animals; Streptococcus gordonii; Periodontitis; Mice; Male; Female; Mice, Inbred C57BL; Streptococcal Infections; Gingiva; Gene Expression Regulation; Alveolar Bone Loss; Gene Expression Profiling; Kinetics
PubMed: 38892405
DOI: 10.3390/ijms25116217 -
International Journal of Molecular... Jun 2024Dementia, a multifaceted neurological syndrome characterized by cognitive decline, poses significant challenges to daily functioning. The main causes of dementia,... (Review)
Review
Dementia, a multifaceted neurological syndrome characterized by cognitive decline, poses significant challenges to daily functioning. The main causes of dementia, including Alzheimer's disease (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and vascular dementia (VD), have different symptoms and etiologies. Genetic regulators, specifically non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are known to play important roles in dementia pathogenesis. MiRNAs, small non-coding RNAs, regulate gene expression by binding to the 3' untranslated regions of target messenger RNAs (mRNAs), while lncRNAs and circRNAs act as molecular sponges for miRNAs, thereby regulating gene expression. The emerging concept of competing endogenous RNA (ceRNA) interactions, involving lncRNAs and circRNAs as competitors for miRNA binding, has gained attention as potential biomarkers and therapeutic targets in dementia-related disorders. This review explores the regulatory roles of ncRNAs, particularly miRNAs, and the intricate dynamics of ceRNA interactions, providing insights into dementia pathogenesis and potential therapeutic avenues.
Topics: Humans; Dementia; MicroRNAs; RNA, Circular; Gene Expression Regulation; RNA, Long Noncoding; RNA, Untranslated; Animals; Biomarkers; Alzheimer Disease
PubMed: 38892378
DOI: 10.3390/ijms25116190 -
International Journal of Molecular... Jun 2024Parkinson's disease is a progressive neurodegenerative disorder, predominantly of the motor system. Although some genetic components and cellular mechanisms of... (Review)
Review
Parkinson's disease is a progressive neurodegenerative disorder, predominantly of the motor system. Although some genetic components and cellular mechanisms of Parkinson's have been identified, much is still unknown. In recent years, emerging evidence has indicated that non-DNA-sequence variation (in particular epigenetic mechanisms) is likely to play a crucial role in the development and progression of the disease. Here, we present an up-to-date overview of epigenetic processes including DNA methylation, DNA hydroxymethylation, histone modifications and non-coding RNAs implicated in the brain of those with Parkinson's disease. We will also discuss the limitations of current epigenetic research in Parkinson's disease, the advantages of simultaneously studying genetics and epigenetics, and putative novel epigenetic therapies.
Topics: Parkinson Disease; Humans; Epigenesis, Genetic; DNA Methylation; Brain; RNA, Untranslated; Animals; Histone Code; Histones
PubMed: 38892355
DOI: 10.3390/ijms25116168 -
International Journal of Molecular... Jun 2024() is the causative agent of bovine tuberculosis (bTb). Genetic selection aiming to identify less susceptible animals has been proposed as a complementary measure in...
Genome-Wide Association Study Reveals Quantitative Trait Loci and Candidate Genes Associated with High Interferon-gamma Production in Holstein Cattle Naturally Infected with .
() is the causative agent of bovine tuberculosis (bTb). Genetic selection aiming to identify less susceptible animals has been proposed as a complementary measure in ongoing programs toward controlling infection. However, individual animal phenotypes for bTb based on interferon-gamma (IFNɣ) and its use in bovine selective breeding programs have not been explored. In the current study, IFNɣ production was measured using a specific IFNɣ ELISA kit in bovine purified protein derivative (bPPD)-stimulated blood samples collected from Holstein cattle. DNA isolated from the peripheral blood samples collected from the animals included in the study was genotyped with the EuroG Medium Density bead Chip, and the genotypes were imputed to whole-genome sequences. A genome-wide association analysis (GWAS) revealed that the IFNɣ in response to bPPD was associated with a specific genetic profile (heritability = 0.23) and allowed the identification of 163 SNPs, 72 quantitative trait loci (QTLs), 197 candidate genes, and 8 microRNAs (miRNAs) associated with this phenotype. No negative correlations between this phenotype and other phenotypes and traits included in the Spanish breeding program were observed. Taken together, our results define a heritable and distinct immunogenetic profile associated with strong production of IFNɣ in response to .
Topics: Animals; Cattle; Quantitative Trait Loci; Mycobacterium bovis; Genome-Wide Association Study; Interferon-gamma; Tuberculosis, Bovine; Polymorphism, Single Nucleotide; Phenotype; Genotype
PubMed: 38892353
DOI: 10.3390/ijms25116165 -
International Journal of Molecular... Jun 2024Noncoding RNAs (ncRNAs) are a class of nucleotide sequences that cannot be translated into peptides. ncRNAs can function post-transcriptionally by splicing complementary... (Review)
Review
Noncoding RNAs (ncRNAs) are a class of nucleotide sequences that cannot be translated into peptides. ncRNAs can function post-transcriptionally by splicing complementary sequences of mRNAs or other ncRNAs or by directly engaging in protein interactions. Over the past few decades, the pervasiveness of ncRNAs in cell physiology and their pivotal roles in various diseases have been identified. One target regulated by ncRNAs is connexin (Cx), a protein that forms gap junctions and hemichannels and facilitates intercellular molecule exchange. The aberrant expression and misdistribution of connexins have been implicated in central nervous system diseases, cardiovascular diseases, bone diseases, and cancer. Current databases and technologies have enabled researchers to identify the direct or indirect relationships between ncRNAs and connexins, thereby elucidating their correlation with diseases. In this review, we selected the literature published in the past five years concerning disorders regulated by ncRNAs via corresponding connexins. Among it, microRNAs that regulate the expression of Cx43 play a crucial role in disease development and are predominantly reviewed. The distinctive perspective of the ncRNA-Cx axis interprets pathology in an epigenetic manner and is expected to motivate research for the development of biomarkers and therapeutics.
Topics: Humans; RNA, Untranslated; Animals; Connexins; MicroRNAs; Connexin 43; Neoplasms; Gene Expression Regulation; Cardiovascular Diseases; Gap Junctions; Central Nervous System Diseases
PubMed: 38892334
DOI: 10.3390/ijms25116146 -
International Journal of Molecular... Jun 2024The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early... (Review)
Review
The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies.
Topics: Humans; Pregnancy; Female; Biomarkers; Pregnancy Trimester, First; Placenta; Pregnancy Outcome; Pre-Eclampsia; MicroRNAs; Pregnancy-Associated Plasma Protein-A; Diabetes, Gestational
PubMed: 38892323
DOI: 10.3390/ijms25116136 -
International Journal of Molecular... Jun 2024The increasing demand placed on professional athletes to enhance their fitness and performance has prompted the search for new, more sensitive biomarkers of...
The increasing demand placed on professional athletes to enhance their fitness and performance has prompted the search for new, more sensitive biomarkers of physiological ability. One such potential biomarker includes microRNA (miRNA) small regulatory RNA sequences. The study investigated the levels of the selected circulating miRNAs before and after a 10-week training cycle in 12 professional female volleyball players, as well as their association with cortisol, creatine kinase (CK), and interleukin 6 (IL-6), using the qPCR technique. Significant decreases in the miR-22 (0.40 ± 0.1 vs. 0.28 ± 0.12, = 0.009), miR-17 (0.35 ± 0.13 vs. 0.23 ± 0.08; = 0.039), miR-24 (0.09 ± 0.04 vs. 0.05 ± 0.02; = 0.001), and miR-26a (0.11 ± 0.06 vs. 0.06 ± 0.04; = 0.003) levels were observed after training, alongside reduced levels of cortisol and IL-6. The correlation analysis revealed associations between the miRNAs' relative quantity and the CK concentrations, highlighting their potential role in the muscle repair processes. The linear regression analysis indicated that miR-24 and miR-26a had the greatest impact on the CK levels. The study provides insights into the dynamic changes in the miRNA levels during training, suggesting their potential as biomarkers for monitoring the adaptive responses to exercise. Overall, the findings contribute to a better understanding of the physiological effects of exercise and the potential use of miRNAs, especially miR-24 and miR-26a, as biomarkers in sports science and medicine.
Topics: Humans; Female; Circulating MicroRNA; Volleyball; Biomarkers; Creatine Kinase; Athletes; Adult; Interleukin-6; Hydrocortisone; Adaptation, Physiological; Young Adult; MicroRNAs
PubMed: 38892295
DOI: 10.3390/ijms25116107 -
International Journal of Molecular... Jun 2024Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder associated with muscle wasting and degeneration. The disease is caused by mutations in the gene... (Review)
Review
Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder associated with muscle wasting and degeneration. The disease is caused by mutations in the gene that encodes dystrophin, a protein that links the cytoskeleton with cell membrane proteins. The current treatment methods aim to relieve the symptoms of the disease or partially rescue muscle functionality. However, they are insufficient to suppress disease progression. In recent years, studies have uncovered an important role for non-coding RNAs (ncRNAs) in regulating the progression of numerous diseases. ncRNAs, such as micro-RNAs (miRNAs), bind to their target messenger RNAs (mRNAs) to suppress translation. Understanding the mechanisms involving dysregulated miRNAs can improve diagnosis and suggest novel treatment methods for patients with DMD. This review presents the available evidence on the role of altered expression of miRNAs in the pathogenesis of DMD. We discuss the involvement of these molecules in the processes associated with muscle physiology and DMD-associated cardiomyopathy.
Topics: Muscular Dystrophy, Duchenne; Humans; MicroRNAs; Animals; Dystrophin; Gene Expression Regulation; Muscle, Skeletal
PubMed: 38892293
DOI: 10.3390/ijms25116108