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Journal of Clinical Laboratory Analysis Jul 2022The incidence of premature atherosclerotic cardiovascular disease in familial hypercholesterolemia (FH) is high. In recent years, novel therapeutic modalities have shown... (Review)
Review
BACKGROUND
The incidence of premature atherosclerotic cardiovascular disease in familial hypercholesterolemia (FH) is high. In recent years, novel therapeutic modalities have shown significant lipid-lowering ability. In this paper, we summarize the recent developments in novel therapies for FH via the treatment of different targets and discuss the characteristics of each targeted therapy. Based on the process of protein synthesis, we attempt to summarize the direct-effect targets including protein, RNA, and DNA.
METHODS
For this systematic review, relevant studies are assessed by searching in several databases including PubMed, Web of Science, Scopus, and Google Scholar. The publications of original researches are considered for screening.
RESULTS
Most drugs are protein-targeted such as molecule-based and monoclonal antibodies, including statins, ezetimibe, alirocumab, evolocumab, and evinacumab. Both antisense oligonucleotide (ASO) and small interfering RNA (siRNA) approaches, such as mipomersen, vupanorsen, inclisiran, and ARO-ANG3, are designed to reduce the number of mRNA transcripts and then degrade proteins. DNA-targeted therapies such as adeno-associated virus or CRISPR-Cas9 modification could be used to deliver or edit genes to address a genetic deficiency and improve the related phenotype.
CONCLUSION
While the therapies based on different targets including protein, RNA, and DNA are on different stages of development, the mechanisms of these novel therapies may provide new ideas for precision medicine.
Topics: Anticholesteremic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Oligonucleotides, Antisense; RNA
PubMed: 35712827
DOI: 10.1002/jcla.24552 -
BMC Cardiovascular Disorders Oct 2023Aortic dissection (AD) is a serious and fatal vascular disease. The earlier the condition of AD patients can be assessed precisely, the more scientifically controlled... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aortic dissection (AD) is a serious and fatal vascular disease. The earlier the condition of AD patients can be assessed precisely, the more scientifically controlled the patient's condition will be. Therefore, timely and accurate diagnosis is significant for AD. Blood biomarker testing as a method of liquid biopsy can improve the diagnostic efficiency of AD. This study conducted a systematic review of the current blood diagnostic biomarkers of AD.
METHODS
The PubMed, Cochrane Library, Web of Science, and Embase electronic databases were systematically searched from inception to January 1, 2023, using the terms "aortic dissection", "serum", "plasma" and "diagnosis". Stata 12.0 software was used to perform Random effects meta-analysis was performed using Stata 12.0 software to determine the effect sizes and corresponding 95% confidence intervals. Then, a summary receiver operator characteristic (SROC) curve was drawn, and the area under the ROC curve (AUC) was calculated.
RESULTS
D-dimer had the best sensitivity and AUC for AD, with values of 0.96 (95% CI: 0.93-0.98) and 0.95 (95% CI: 0.93-0.97), respectively. The sensitivity and AUC values for D-dimer with a cut-off value of 500 ng/mL were 0.97 (95% CI: 0.95-0.99) and 0.94 (95% CI: 0.92-0.96), respectively. In contrast, microRNA had a better specificity value for AD, at 0.79 (95% CI: 0.73-0.83).
CONCLUSIONS
D-dimer and microRNA have good accuracy in the diagnosis of AD, but the specificity of D-dimer is worse, and studies of microRNA are insufficient. The combination of different biomarkers can improve the diagnostic accuracy. Other blood biomarkers are related to the pathological progression of AD and can be selected according to pathological progress.
Topics: Humans; Aortic Dissection; MicroRNAs; Biomarkers; Sensitivity and Specificity
PubMed: 37817089
DOI: 10.1186/s12872-023-03448-9 -
International Journal of Molecular... Nov 2022Plant miRNAs are powerful regulators of gene expression at the post-transcriptional level, which was repeatedly proved in several model plant species. miRNAs are... (Review)
Review
Plant miRNAs are powerful regulators of gene expression at the post-transcriptional level, which was repeatedly proved in several model plant species. miRNAs are considered to be key regulators of many developmental, homeostatic, and immune processes in plants. However, our understanding of plant miRNAs is still limited, despite the fact that an increasing number of studies have appeared. This systematic review aims to summarize our current knowledge about miRNAs in spring barley (), which is an important agronomical crop worldwide and serves as a common monocot model for studying abiotic stress responses as well. This can help us to understand the connection between plant miRNAs and (not only) abiotic stresses in general. In the end, some future perspectives and open questions are summarized.
Topics: Hordeum; MicroRNAs; Stress, Physiological; Plants; Gene Expression Regulation, Plant
PubMed: 36499082
DOI: 10.3390/ijms232314755 -
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 -
PloS One 2023Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.
OBJECTIVE
The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.
METHODS
Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.
RESULTS
In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01).
CONCLUSION
PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.
Topics: Humans; PCSK9 Inhibitors; Cholesterol, LDL; Myocardial Infarction; Proprotein Convertase 9; Atherosclerosis; Heart Disease Risk Factors; RNA, Small Interfering; Anticholesteremic Agents; Cardiovascular Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38055686
DOI: 10.1371/journal.pone.0295359 -
PLoS Neglected Tropical Diseases May 2018Mosquitoes are incriminated as vectors for many crippling diseases, including malaria, West Nile fever, Dengue fever, and other neglected tropical diseases (NTDs).... (Review)
Review
Mosquitoes are incriminated as vectors for many crippling diseases, including malaria, West Nile fever, Dengue fever, and other neglected tropical diseases (NTDs). microRNAs (miRNAs) can interact with multiple target genes to elicit biological functions in the mosquitoes. However, characterization and function of individual miRNAs and their potential targets have not been fully determined to date. We conducted a systematic review of published literature following PRISMA guidelines. We summarize the information about miRNAs in mosquitoes to better understand their metabolism, development, and responses to microorganisms. Depending on the study, we found that miRNAs were dysregulated in a species-, sex-, stage-, and tissue/organ-specific manner. Aberrant miRNA expressions were observed in development, metabolism, host-pathogen interactions, and insecticide resistance. Of note, many miRNAs were down-regulated upon pathogen infection. The experimental studies have expanded the identification of miRNA target from the 3' untranslated regions (UTRs) of mRNAs of mosquitoes to the 5' UTRs of mRNAs of the virus. In addition, we discuss current trends in mosquito miRNA research and offer suggestions for future studies.
Topics: Animals; Culicidae; Insect Vectors; MicroRNAs
PubMed: 29718912
DOI: 10.1371/journal.pntd.0006463 -
Brain Research Bulletin Mar 2023MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression... (Meta-Analysis)
Meta-Analysis Review
MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression in patients with amyotrophic lateral sclerosis (ALS). Clinical data also confirmed that miRNAs in these patients are inconsistent across studies. A comprehensive systematic review and meta-analysis of current studies can help recognize the important roles of miRNAs during ALS development. Therefore, we initially aimed to perform a systematic literature review on the muscle or serum miRNAs in patients with ALS and healthy individuals. Subsequently, we quantitatively summarized the clinical data of muscle or serum miRNA of patients with ALS and healthy individuals using a meta-analytical technique. 11 studies comprising 281 patients with ALS and 244 healthy control (HC) controls were identified from PubMed and Web of Science for meta-analysis. A systematic review revealed that miRNA levels are closely associated with the occurrence of ALS disease. The expression levels of the most relevant miRNAs were either increased or decreased. The random-effects meta-analysis indicated that the levels of miR-206, miR-133b, and miR-338-3p were significantly elevated in patients with ALS than in HC subjects. By contrast, there was no significant differences in the miR-133a levels between patients with ALS and HC subjects. Collectively, our outcomes demonstrated that serum miR-206, miR-133b, and miR-338-3p were significantly increased in patients with ALS. We speculated that the increased expression levels of miR-206, miR-133b and miR-338-3p are potential promising biomarkers for ALS.
Topics: Humans; MicroRNAs; Amyotrophic Lateral Sclerosis; Biomarkers
PubMed: 36681253
DOI: 10.1016/j.brainresbull.2023.01.005 -
Journal of Stroke and Cerebrovascular... Nov 2023Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive biomarker assays of both non-coding RNA- and protein biomarkers have improved their detectability, which could accelerate stroke diagnosis. This systematic review and meta-analysis compares non-coding RNA- with protein biomarkers for their potential to diagnose and differentiate acute stroke (subtypes) in (pre-)hospital settings.
METHODS
We performed a systematic review and meta-analysis of studies evaluating diagnostic performance of non-coding RNA- and protein biomarkers to differentiate acute ischemic and hemorrhagic stroke, stroke mimics, and (healthy) controls. Quality appraisal of individual studies was assessed using the QUADAS-2 tool while the meta-analysis was performed with the sROC approach and by assessing pooled sensitivity and specificity, diagnostic odds ratios, positive- and negative likelihood ratios, and the Youden Index.
SUMMARY OF REVIEW
112 studies were included in the systematic review and 42 studies in the meta-analysis containing 11627 patients with ischemic strokes, 2110 patients with hemorrhagic strokes, 1393 patients with a stroke mimic, and 5548 healthy controls. Proteins (IL-6 and S100 calcium-binding protein B (S100B)) and microRNAs (miR-30a) have similar performance in ischemic stroke diagnosis. To differentiate between ischemic- or hemorrhagic strokes, glial fibrillary acidic protein (GFAP) levels and autoantibodies to the NR2 peptide (NR2aAb, a cleavage product of NMDA neuroreceptors) were best performing whereas no investigated protein or non-coding RNA biomarkers differentiated stroke from stroke mimics with high diagnostic potential.
CONCLUSIONS
Despite sampling time differences, circulating microRNAs (< 24 h) and proteins (< 4,5 h) perform equally well in ischemic stroke diagnosis. GFAP differentiates stroke subtypes, while a biomarker panel of GFAP and UCH-L1 improved the sensitivity and specificity of UCH-L1 alone to differentiate stroke.
Topics: Humans; Hemorrhagic Stroke; Stroke; Biomarkers; Ischemic Stroke; Glial Fibrillary Acidic Protein; MicroRNAs; RNA, Untranslated
PubMed: 37778160
DOI: 10.1016/j.jstrokecerebrovasdis.2023.107388 -
Animal Models and Experimental Medicine Feb 2022Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single-stranded transcript. They are a novel class of genomic regulators that are linked to many... (Review)
Review
Circular RNAs (circRNAs) are endogenous RNAs with a covalently closed single-stranded transcript. They are a novel class of genomic regulators that are linked to many important development and disease processes and are being pursued as clinical and therapeutic targets. Using the most powerful RNA sequencing and bioinformatics techniques, a large number of circRNAs have been identified and further functional studies have been performed. It is known that circRNAs act as potential biomarkers, sponges for microRNAs (miRNAs) and RNA-binding proteins (RBPs), and regulators of mRNA transcription. They also participate in the translation of peptides or proteins. Many types of circRNAs are dysregulated in plasma or lung tissues, and they may be involved in regulating the proliferation and apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs), leading to pulmonary vascular remodeling in pulmonary hypertension (PH). One possible mechanism is that circRNAs can regulate the function of PAECs and PASMCs by acting as miRNA sponge. However, other potential mechanisms of action of circRNAs are still being actively explored in PH. This paper presents a systematic review of the biogenesis, biological characterization, relevant underlying functions, and future perspectives for studies of circRNAs in the pathogenesis of PH.
Topics: Computational Biology; Endothelial Cells; Humans; Hypertension, Pulmonary; MicroRNAs; RNA, Circular
PubMed: 35229989
DOI: 10.1002/ame2.12208 -
European Journal of Clinical... Nov 2022Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta-analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG.
METHODS
Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022.
RESULTS
Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: -73.9%; 95%CI: -93.5%, -54.2; p < .001 I = 89.05%; p < .001); VLDL-C level (MD: -71.0%; 95%CI: -76.6%, -65.4%; p < .001 I = 94.1%; p < .001); Apo-B48 level (MD: -69.03%; 95%CI: -98.59.4%, -39.47%; p < .001, I = 93.51%; p < .001) and Apo-CIII level (MD: -80.0%; 95%CI: -97.5%, -62.5; p < .001 I = 94.1%; p < .001) with an increase in HDL-C level (MD: +45.92%, 95%CI: +37.24%, +54.60%; p < .001 I = 94.34%; p < .001) and in LDL-C level (MD: +68.6%, 95%CI: +7.0%, +130.1%; p < .001 I = 96.18%; p < .001) without a significant elevation of Apo-B100 level (MD: +4.58%, 95%CI: -5.64%, +14.79%; p = .380 I = 95.09%; p < .001) in 139 volanesorsen patients as compared to 100 placebo-treated controls. Most of adverse events were mild and related to local injection site reactions.
CONCLUSIONS
In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL-C, Apo-B48 and non-HDL-C and increment of HDL-C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile.
Topics: Apolipoprotein B-48; Apolipoprotein C-III; Cholesterol, LDL; Humans; Hyperlipidemias; Hypertriglyceridemia; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 35851450
DOI: 10.1111/eci.13841