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International Journal of Molecular... Dec 2023Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high... (Review)
Review
Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.
Topics: Humans; MicroRNAs; Substance-Related Disorders; Behavior, Addictive; Brain
PubMed: 38069445
DOI: 10.3390/ijms242317122 -
International Journal of Molecular... Nov 2023The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the... (Review)
Review
The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the literature by searching PubMed, Web of Science, and ProQuest databases for genes, proteins, and microRNAs associated with MRONJ from the earliest records through April 2023. Conference abstracts, letters, review articles, non-human studies, and non-English publications were excluded. Twelve studies meeting the inclusion criteria involving exposure of human oral mucosa, blood, serum, saliva, or adjacent bone or periodontium to anti-resorptive or anti-angiogenic agents were analyzed. The Cochrane Collaboration risk assessment tool was used to assess the quality of the studies. A total of 824 differentially expressed genes/proteins (DEGs) and 22 microRNAs were extracted for further bioinformatic analysis using Cytoscape, STRING, BiNGO, cytoHubba, MCODE, and ReactomeFI software packages and web-based platforms: DIANA mirPath, OmicsNet, and miRNet tools. The analysis yielded an interactome consisting of 17 hub genes and hsa-mir-16-1, hsa-mir-21, hsa-mir-23a, hsa-mir-145, hsa-mir-186, hsa-mir-221, and hsa-mir-424. A dominance of cytokine pathways was observed in both the cluster of hub DEGs and the interactome of hub genes with dysregulated miRNAs. In conclusion, a panel of genes, miRNAs, and related pathways were found, which is a step toward understanding the complexity of the disease.
Topics: Humans; MicroRNAs; Osteonecrosis; Computational Biology; Gene Regulatory Networks
PubMed: 38069068
DOI: 10.3390/ijms242316745 -
Environmental Research Mar 2024Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is... (Review)
Review
Per- and polyfluoroalkyl substances, polychlorinated biphenyls, organochlorine pesticides, and polybrominated diphenyl ethers and dysregulation of MicroRNA expression in humans and animals-A systematic review.
BACKGROUND
Persistent organic pollutants (POPs) are chemicals characterized by their environmental persistence. Evidence suggests that exposure to POPs, which is ubiquitous, is associated with microRNA (miRNA) dysregulation. miRNA are key regulators in many physiological processes. It is thus of public health concern to understand the relationships between POPs and miRNA as related to health outcomes.
OBJECTIVES
This systematic review evaluated the relationship between widely recognized, intentionally manufactured, POPs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB]), with miRNA expression in both human and animal studies.
METHODS
We used PubMed and Embase to systematically search the literature up to September 29th, 2023. Search results for human and animal studies were included if they incorporated at least one POP of interest in relation to at least one miRNA. Data were synthesized to determine the direction and significance of associations between POPs and miRNA. We utilized ingenuity pathway analysis to review disease pathways for miRNA that were associated with POPs.
RESULTS
Our search identified 38 eligible studies: 9 in humans and 29 in model organisms. PFAS were associated with decreased expression of miR-19, miR-193b, and miR-92b, as well as increased expression of miR-128, miR-199a-3p, and miR-26b across species. PCBs were associated with increased expression of miR-15a, miR-1537, miR-21, miR-22-3p, miR-223, miR-30b, and miR-34a, as well as decreased expression of miR-130a and let-7b in both humans and animals. Pathway analysis for POP-associated miRNA identified pathways related to carcinogenesis.
DISCUSSION
This is the first systematic review of the association of POPs with miRNA in humans and model organisms. Large-scale prospective human studies are warranted to examine the role of miRNA as mediators between POPs and health outcomes.
Topics: Animals; Humans; Polychlorinated Biphenyls; Halogenated Diphenyl Ethers; Prospective Studies; Hydrocarbons, Chlorinated; Environmental Pollutants; Pesticides; MicroRNAs; Fluorocarbons
PubMed: 38056610
DOI: 10.1016/j.envres.2023.117832 -
Journal of Investigative Surgery : the... Dec 2023This study aims to investigate the association between miR-203 expression and the prognostic value in patients with esophageal cancer by the method of systematic review... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aims to investigate the association between miR-203 expression and the prognostic value in patients with esophageal cancer by the method of systematic review and meta-analysis.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane Library to collect studies on the relationship between miR-203 expression and the prognostic value of esophageal cancer up to July 2023. Stata 15.0 statistical software was used for data analysis. Hazard ratio (HR) and 95% confidence interval (CI) were used as effect sizes.
RESULTS
A total of 6 studies were included in this review, including 476 patients with esophageal cancer. The results showed that miR-203 low expression was associated with worse overall survival (OS) in patients with esophageal cancer compared with miR-203 high expression (HR = 2.80, 95%CI: 1.99 ∼ 3.93, < 0.001). The results of Egger's ( = 0.154) and Begg's Tests ( = 0.221) indicated no obvious publication bias. Sensitivity analysis verified the robustness of the results obtained in this study.
CONCLUSION
The expression of miR-203 is significantly correlated with the prognostic value in patients with esophageal cancer. Esophageal cancer patients with high expression of miR-203 had better prognosis than those with low expression of miR-203. Due to the limited studies included in this meta-analysis, more trials are needed to confirm the conclusions of this study in the future.
Topics: Humans; Prognosis; Esophageal Neoplasms; Biomarkers, Tumor; MicroRNAs
PubMed: 38047456
DOI: 10.1080/08941939.2023.2285780 -
International Journal of Stem Cells Nov 2023Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal... (Review)
Review
Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.
PubMed: 38016704
DOI: 10.15283/ijsc23092 -
BMC Geriatrics Nov 2023Delirium is a prevalent neuropsychiatric medical phenomenon that causes serious emergency outcomes, including mortality and morbidity. It also increases the suffering...
Exploration of key drug target proteins highlighting their related regulatory molecules, functional pathways and drug candidates associated with delirium: evidence from meta-data analyses.
BACKGROUND
Delirium is a prevalent neuropsychiatric medical phenomenon that causes serious emergency outcomes, including mortality and morbidity. It also increases the suffering and the economic burden for families and carers. Unfortunately, the pathophysiology of delirium is still unknown, which is a major obstacle to therapeutic development. The modern network-based system biology and multi-omics analysis approach has been widely used to recover the key drug target biomolecules and signaling pathways associated with disease pathophysiology. This study aimed to identify the major drug target hub-proteins associated with delirium, their regulatory molecules with functional pathways, and repurposable drug candidates for delirium treatment.
METHODS
We used a comprehensive proteomic seed dataset derived from a systematic literature review and the Comparative Toxicogenomics Database (CTD). An integrated multi-omics network-based bioinformatics approach was utilized in this study. The STRING database was used to construct the protein-protein interaction (PPI) network. The gene set enrichment and signaling pathways analysis, the regulatory transcription factors and microRNAs were conducted using delirium-associated genes. Finally, hub-proteins associated repurposable drugs were retrieved from CMap database.
RESULTS
We have distinguished 11 drug targeted hub-proteins (MAPK1, MAPK3, TP53, JUN, STAT3, SRC, RELA, AKT1, MAPK14, HSP90AA1 and DLG4), 5 transcription factors (FOXC1, GATA2, YY1, TFAP2A and SREBF1) and 6 microRNA (miR-375, miR-17-5, miR-17-5p, miR-106a-5p, miR-125b-5p, and miR-125a-5p) associated with delirium. The functional enrichment and pathway analysis revealed the cytokines, inflammation, postoperative pain, oxidative stress-associated pathways, developmental biology, shigellosis and cellular senescence which are closely connected with delirium development and the hallmarks of aging. The hub-proteins associated computationally identified repurposable drugs were retrieved from database. The predicted drug molecules including aspirin, irbesartan, ephedrine-(racemic), nedocromil, and guanidine were characterized as anti-inflammatory, stimulating the central nervous system, neuroprotective medication based on the existing literatures. The drug molecules may play an important role for therapeutic development against delirium if they are investigated more extensively through clinical trials and various wet lab experiments.
CONCLUSION
This study could possibly help future research on investigating the delirium-associated therapeutic target biomarker hub-proteins and repurposed drug compounds. These results will also aid understanding of the molecular mechanisms that underlie the pathophysiology of delirium onset and molecular function.
Topics: Humans; Gene Regulatory Networks; Proteomics; MicroRNAs; Transcription Factors; Delirium
PubMed: 37993790
DOI: 10.1186/s12877-023-04457-1 -
Medicine Nov 2023Lung cancer is the leading cause of death worldwide, and its diagnosis remains a significant challenge. Identifying effective methods to differentiate benign from... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lung cancer is the leading cause of death worldwide, and its diagnosis remains a significant challenge. Identifying effective methods to differentiate benign from malignant lung nodules is of paramount importance. This meta-analysis aimed to evaluate the clinical utility of circulating microRNAs (miRNAs) for the differential diagnosis of benign and malignant lung nodules.
METHODS
This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search was conducted across 4 electronic databases, without any temporal restrictions. The inclusion and exclusion criteria were strictly applied to assess the clinical applications of circulating miRNAs. A robust and transparent quality assessment was performed using the quality assessment of diagnostic accuracy studies-2 tool, and rigorous statistical analyses were conducted to synthesize the various diagnostic measures.
RESULTS
In the meta-analysis of 11 studies, quality assessment of diagnostic accuracy studies-2 assessment revealed < 5% high-risk methodologies, ensuring robustness. Sensitivity and Specificity were consolidated at 0.83 (95% confidence interval [CI]: 0.72-0.90) and 0.81 (95% CI: 0.73-0.88), respectively. The positive likelihood ratio and negative likelihood ratio were 4.45 (95% CI: 3.03-6.54) and 0.21 (95% CI: 0.12-0.35), respectively. The diagnostic odds ratio was 21.31 (95% CI: 10.25-44.30) and area under the receiver operating characteristic curve was 0.89 (95% CI: 0.86-0.91). Subgroup analysis highlighted significant variations in diagnostic accuracy by ethnicity and miRNA source, with non-Asian populations and serum-based tests showing higher diagnostic accuracy.
CONCLUSION
This meta-analysis demonstrated that circulating miRNAs hold substantial diagnostic value in distinguishing between benign and malignant lung nodules.
Topics: Humans; MicroRNAs; Sensitivity and Specificity; ROC Curve; Circulating MicroRNA; Lung
PubMed: 37986348
DOI: 10.1097/MD.0000000000035857 -
BMC Cancer Nov 2023RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial.
METHODS
We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups.
RESULTS
Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47-5.73) and 2.69 (1.82-3.98)] and OS [HRs = 2.66 (1.95-3.65) and 2.45 (1.55-3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (P < 0.01 for PFS). Patients with tumors with any mutation in the KRAS/NRAS/BRAF/PIK3CA gene also showed similar results compared with all wild-type tumors (P for PFS, OS, and ORR were < 0.01, < 0.01 and 0.01, respectively). While low miR-31-3p expression could predict PFS (P = 0.01) and OS (P = 0.04) benefit. The prognostic and predictive value regarding PIK3CA mutations, PTEN mutations or deletions, EGFR, EREG/AREG, HER2, HER3, and HER4 expression remains uncertain.
CONCLUSIONS
In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.
Topics: Humans; Prognosis; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); ErbB Receptors; Antibodies, Monoclonal; Colonic Neoplasms; Rectal Neoplasms; Biomarkers; Class I Phosphatidylinositol 3-Kinases; Mutation; MicroRNAs; Biomarkers, Tumor
PubMed: 37974093
DOI: 10.1186/s12885-023-11600-z -
Association of noncoding RNAs with Kawasaki disease: A meta-analysis based on the current evidences.Medicine Nov 2023In recent years, many studies have focused on the relationship between noncoding RNAs (ncRNAs) and Kawasaki disease (KD). Studies have indicated that ncRNAs are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In recent years, many studies have focused on the relationship between noncoding RNAs (ncRNAs) and Kawasaki disease (KD). Studies have indicated that ncRNAs are associated with the occurrence and development of KD. Thus, we performed a systematic review and meta-analysis to investigate the diagnostic value of ncRNAs in KD patients.
METHODS
We searched the PubMed, Web of Science, Embase and Cochrane Library, China National Knowledge Infrastructure, VIP, China Biology Medicine disc databases, and Wanfang databases until August 25, 2023 and screened all eligible studies focusing on the diagnostic performance of ncRNAs in KD patients.
RESULTS
In total, 535 articles were found, and 28 articles were included in this systematic review and meta-analysis. The calculated area under the curve value was 0.880 (95% confidence intervals, 0.840-0.900). The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.790, 0.830, 4.610, and 0.260, respectively. The pooled diagnostic odds ratio was 17.890 (95% confidence intervals, 13.110-24.420), indicating a relatively good diagnostic performance of the ncRNAs for detecting KD. In addition, the diagnostic value of micro RNAs in KD was better than that of long noncoding RNAs and circular noncoding RNAs. A subgroup analysis by specimen indicated a better diagnostic value of ncRNAs in plasma and platelet than serum. The diagnostic accuracy of ncRNAs was better in febrile controls than in healthy control groups, indicating a relatively good accuracy in distinguishing KD patients from febrile diseases.
CONCLUSIONS
This systematic review and meta-analysis demonstrated that ncRNAs could be used as novel biomarkers for detecting KD. More studies should be conducted in the future to verify the diagnostic values of ncRNAs in KD.
Topics: Humans; Mucocutaneous Lymph Node Syndrome; Sensitivity and Specificity; Biomarkers; MicroRNAs; RNA, Circular
PubMed: 37960719
DOI: 10.1097/MD.0000000000035736 -
International Journal of Molecular... Oct 2023Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance....
Circulating extracellular vesicle (EV)-derived microRNAs (miRNAs) are now considered the next generation of cancer "theranostic" tools, with strong clinical relevance. Although their potential in breast cancer diagnosis has been widely reported, further studies are still required to address this challenging issue. The present study examined the expression profiles of EV-packaged miRNAs to identify novel miRNA signatures in breast cancer and verified their diagnostic accuracy. Circulating EVs were isolated from healthy controls and breast cancer patients and characterized following the MISEV 2018 guidelines. RNA-sequencing and real-time PCR showed that miRNA-27a and miRNA-128 were significantly down-regulated in patient-derived EVs compared to controls in screening and validation cohorts. Bioinformatics analyses of miRNA-target genes indicated several enriched biological processes/pathways related to breast cancer. Receiver operating characteristic (ROC) curves highlighted the ability of these EV-miRNAs to distinguish breast cancer patients from non-cancer controls. According to other reports, the levels of EV-miRNA-27a and EV-miRNA-128 are not associated with their circulating ones. Finally, evidence from the studies included in our systematic review underscores how the expression of these miRNAs in biofluids is still underinvestigated. Our findings unraveled the role of serum EV-derived miRNA-27a and miRNA-128 in breast cancer, encouraging further investigation of these two miRNAs within EVs towards improved breast cancer detection.
Topics: Humans; Female; MicroRNAs; Breast Neoplasms; Extracellular Vesicles
PubMed: 37958677
DOI: 10.3390/ijms242115695