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1.
Carbohydr Polym ; 276: 118739, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823775

RESUMO

Adjuvants have been used in vaccines for a long time to promote the body's immune response, reducing vaccine dosage and production costs. Although many vaccine adjuvants are developed, the use in human vaccines is limited because of either limited action or side effects. Therefore, the development of new vaccine adjuvants is required. Many studies have found that natural polysaccharides derived from Traditional Chinese medicine (TCM) possess good immune promoting effects and simultaneously improve humoral, cellular and mucosal immunity. Recently polysaccharide adjuvants have attracted much attention in vaccine preparation because of their intrinsic characteristics: immunomodulation, biocompatibility, biodegradability, low toxicity and safety. This review article systematically analysed the literature on polysaccharides possessing vaccine adjuvant activity from TCM plants, such as Astragalus polysaccharide (APS), Rehmannia glutinosa polysaccharide (RGP), Isatis indigotica root polysaccharides (IRPS), etc. and their derivatives. We believe that polysaccharide adjuvants can be used to prepare the vaccines for clinical use provided their mechanisms of action are studied in detail.

2.
Proc Natl Acad Sci U S A ; 118(48)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34810252

RESUMO

Vascular endothelial cells are exposed to shear stresses with disturbed vs. laminar flow patterns, which lead to proinflammatory vs. antiinflammatory phenotypes, respectively. Effective treatment against endothelial inflammation and the consequent atherogenesis requires the identification of new therapeutic molecules and the development of drugs targeting these molecules. Using Connectivity Map, we have identified vitexin, a natural flavonoid, as a compound that evokes the gene-expression changes caused by pulsatile shear, which mimics laminar flow with a clear direction, vs. oscillatory shear (OS), which mimics disturbed flow without a clear direction. Treatment with vitexin suppressed the endothelial inflammation induced by OS or tumor necrosis factor-α. Administration of vitexin to mice subjected to carotid partial ligation blocked the disturbed flow-induced endothelial inflammation and neointimal formation. In hyperlipidemic mice, treatment with vitexin ameliorated atherosclerosis. Using SuperPred, we predicted that apurinic/apyrimidinic endonuclease1 (APEX1) may directly interact with vitexin, and we experimentally verified their physical interactions. OS induced APEX1 nuclear translocation, which was inhibited by vitexin. OS promoted the binding of acetyltransferase p300 to APEX1, leading to its acetylation and nuclear translocation. Functionally, knocking down APEX1 with siRNA reversed the OS-induced proinflammatory phenotype, suggesting that APEX1 promotes inflammation by orchestrating the NF-κB pathway. Animal experiments with the partial ligation model indicated that overexpression of APEX1 negated the action of vitexin against endothelial inflammation, and that endothelial-specific deletion of APEX1 ameliorated atherogenesis. We thus propose targeting APEX1 with vitexin as a potential therapeutic strategy to alleviate atherosclerosis.

3.
Life (Basel) ; 11(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34833095

RESUMO

The sex chromosomes play central roles in determining the sex of almost all of the multicellular organisms. It is well known that meiosis in mammalian spermatogenesis produces ~50% Y- and ~50% X-chromosome-bearing sperm, a 1:1 ratio. Here we first reveal that the X-chromosome-encoded miRNAs show lower expression levels in the left testis than in the right testis in healthy mice using bioinformatics modeling of miRNA-sequencing data, suggesting that the Y:X ratio could be unbalanced between the left testis and the right testis. We further reveal that the Y:X ratio is significantly elevated in the left testis but balanced in the right testis using flow cytometry. This study represents the first time the biased Y:X ratio in the left testis but not in the right testis is revealed.

4.
Biomedicines ; 9(11)2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34829818

RESUMO

Breast cancer (BC) and colon cancer (CRC) are the two most deadly cancers in the world. These cancers partly share the same genetic background and are partially regulated by the same genes. The outcomes of traditional chemoradiotherapy and surgery remain suboptimal, with high postoperative recurrence and a low survival rate. It is, therefore, urgent to innovate and improve the existing treatment measures. Many studies primarily reported that the microRNA (miRNA) sponge functions of circular RNA (circRNA) in BC and CRC have an indirect relationship between the circRNA-miRNA axis and malignant behaviors. With a covalent ring structure, circRNAs can regulate the expression of target genes in multiple ways, especially by acting as miRNA sponges. Therefore, this review mainly focuses on the roles of circRNAs as miRNA sponges in BC and CRC based on studies over the last three years, thus providing a theoretical reference for finding new therapeutic targets in the future.

5.
Front Pharmacol ; 12: 743623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531754

RESUMO

Respiratory viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-1, SARS-CoV-2, influenza A viruses, and respiratory syncytial virus, pose a serious threat to society. Based on the guiding principles of "holism" and "syndrome differentiation and treatment", traditional Chinese medicine (TCM) has unique advantages in the treatment of respiratory virus diseases owing to the synergistic effect of multiple components and targets, which prevents drug resistance from arising. According to TCM theory, there are two main strategies in antiviral treatments, namely "dispelling evil" and "fu zheng". Dispelling evil corresponds to the direct inhibition of virus growth and fu zheng corresponds to immune regulation, inflammation control, and tissue protection in the host. In this review, current progress in using TCMs against respiratory viruses is summarized according to modern biological theories. The prospects for developing TCMs against respiratory viruses is discussed to provide a reference for the research and development of innovative TCMs with multiple components, multiple targets, and low toxicity.

7.
Pharmaceuticals (Basel) ; 14(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207368

RESUMO

Hemagglutinin (HA) plays a critical role during influenza virus receptor binding and subsequent membrane fusion process, thus HA has become a promising drug target. For the past several decades, we and other researchers have discovered a series of HA inhibitors mainly targeting its fusion machinery. In this review, we summarize the advances in HA-targeted development of small molecule inhibitors. Moreover, we discuss the structural basis and mode of action of these inhibitors, and speculate upon future directions toward more potent inhibitors of membrane fusion and potential anti-influenza drugs.

8.
Brief Bioinform ; 22(6)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226920

RESUMO

Animal models have a certain degree of similarity with human in genes and physiological processes, which leads them to be valuable tools for studying human diseases and for assisting drug development. However, translational researches adopting animal models are largely restricted by the species heterogeneity, which is also a major reason for the failure of drug research. Currently, computational method for exploring the functional differences between orthologous genes is still insufficient. For this purpose, here, we presented an algorithm, functional divergence score (FDS), by comprehensively evaluating the functional differences between the microRNAs regulating the paired orthologous genes. Given that mouse is one of the most popular model animals, currently, FDS was designed to dissect the functional divergence of orthologous genes between human and mouse. The results showed that gene FDS value is significantly associated with gene evolutionary characteristics and can discover expression divergence of human-mouse orthologous genes. Moreover, FDS performed well in distinguishing the targets of approved drugs and the failed ones. These results suggest that FDS is a valuable tool to evaluate the functional divergence of paired human and mouse orthologous genes. In addition, for each orthologous gene pair, FDS can provide detailed differences in functions and phenotypes. Our study provided a useful tool for quantifying the functional difference between human and mouse, and the presented framework is easily to be extended to the orthologous genes between human and other species. An online server of FDS is available at http://www.cuilab.cn/fds/.

9.
Carbohydr Polym ; 269: 118290, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34294316

RESUMO

Glycosaminoglycan HnFG was extracted from sea cucumber Holothuria nobilis. Its chemical structure was characterized by analyzing the physicochemical properties, oligosaccharides from its mild acid hydrolysates and depolymerized products. The disaccharide d-GalNAc4S6S-α1,2-l-Fuc3S-ol found in its mild acid hydrolysates provided a clue for the presence of a unique disaccharide-branch in HnFG. Furthermore, it was confirmed by a series of oligosaccharides from the low-molecular weight HnFG prepared by ß-eliminative depolymerization. Combining with the analysis of its peroxide depolymerized products, the precise structure of HnFG was determined: A chondroitin sulfate E (CS-E)-like backbone branched with sulfated monofucoses (~67%) and disaccharides d-GalNAcS-α1,2-l-Fuc3S (~33%) at O-3 position of each GlcUA. This is the first report on the novel branches in glycosaminoglycan. Biologically, the native and depolymerized HnFG showed potent activities in prolonging the activated partial thrombin time (APTT) and inhibiting intrinsic coagulation Xase (iXase), whereas the oligosaccharides (degree of polymerization ≤6) had no obvious effects.


Assuntos
Anticoagulantes/farmacologia , Glicosaminoglicanos/farmacologia , Holothuria/química , Animais , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Sequência de Carboidratos , Cisteína Endopeptidases , Inibidores de Cisteína Proteinase/química , Inibidores de Cisteína Proteinase/isolamento & purificação , Inibidores de Cisteína Proteinase/farmacologia , Glicosaminoglicanos/química , Glicosaminoglicanos/isolamento & purificação , Humanos , Hidrólise , Proteínas de Neoplasias/antagonistas & inibidores , Oligossacarídeos/química , Relação Estrutura-Atividade , Tempo de Trombina
10.
Circulation ; 144(15): 1244-1261, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34315224

RESUMO

BACKGROUND: How the extracellular matrix (ECM) microenvironment modulates the contractile phenotype of vascular smooth muscle cells (VSMCs) and confers vascular homeostasis remains elusive. METHODS: To explore the key ECM proteins in the maintenance of the contractile phenotype of VSMCs, we applied protein-protein interaction network analysis to explore novel ECM proteins associated with the VSMC phenotype. By combining in vitro and in vivo genetic mice vascular injury models, we identified nidogen-2, a basement membrane glycoprotein, as a key ECM protein for maintenance of vascular smooth muscle cell identity. RESULTS: We collected a VSMC phenotype-related gene dataset by using Gene Ontology annotation combined with a literature search. A computational analysis of protein-protein interactions between ECM protein genes and the genes from the VSMC phenotype-related gene dataset revealed the candidate gene nidogen-2, a basement membrane glycoprotein involved in regulation of the VSMC phenotype. Indeed, nidogen-2-deficient VSMCs exhibited loss of contractile phenotype in vitro, and compared with wild-type mice, nidogen-2-/- mice showed aggravated post-wire injury neointima formation of carotid arteries. Further bioinformatics analysis, coimmunoprecipitation assays, and luciferase assays revealed that nidogen-2 specifically interacted with Jagged1, a conventional Notch ligand. Nidogen-2 maintained the VSMC contractile phenotype via Jagged1-Notch3 signaling but not Notch1 or Notch2 signaling. Nidogen-2 enhanced Jagged1 and Notch3 interaction and subsequent Notch3 activation. Reciprocally, Jagged1 and Notch3 interaction, signaling activation, and Jagged1-triggered VSMC differentiation were significantly repressed in nidogen-2-deficient VSMCs. In accordance, the suppressive effect of Jagged1 overexpression on neointima formation was attenuated in nidogen-2-/- mice compared with wild-type mice. CONCLUSIONS: Nidogen-2 maintains the contractile phenotype of VSMCs through Jagged1-Notch3 signaling in vitro and in vivo. Nidogen-2 is required for Jagged1-Notch3 signaling.

11.
Genes (Basel) ; 12(6)2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207420

RESUMO

In recent years, biofluid has been considered a promising source of non-invasive biomarkers for health monitoring and disease diagnosis. However, the expression consistency between biofluid and human tissue, which is fundamental to RNA biomarker development, has not been fully evaluated. In this study, we collected expression profiles across 53 human tissues and five main biofluid types. Utilizing the above dataset, we uncovered a globally positive correlation pattern between various biofluids (including blood, urine, bile, saliva and stool) and human tissues. However, significantly varied biofluid-tissue similarity levels and tendencies were observed between mRNA and lncRNA. Moreover, a higher correlation was found between biofluid types and their functionally related and anatomically closer tissues. In particular, a highly specific correlation was discovered between urine and the prostate. The biological sex of the donor was also proved to be an important influencing factor in biofluid-tissue correlation. Moreover, genes enriched in basic biological processes were found to display low variability across biofluid types, while genes enriched in catabolism-associated pathways were identified as highly variable.


Assuntos
Líquidos Corporais/metabolismo , Transcriptoma , Biomarcadores/metabolismo , Interpretação Estatística de Dados , Humanos , Especificidade de Órgãos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Bioinformatics ; 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34170294

RESUMO

MOTIVATION: Gene functional enrichment analysis represents one of the most popular bioinformatics methods for annotating the pathways and function categories of a given gene list. Current algorithms for enrichment computation such as Fisher's exact test and hypergeometric test totally depend on the category count numbers of the gene list and one gene set. In this case, whatever the genes are, they were treated equally. However, actually genes show different scores in their essentiality in a gene list and in a gene set. It is thus hypothesized that the essentiality scores could be important and should be considered in gene functional analysis. RESULTS: For this purpose, here we proposed WEAT (https://www.cuilab.cn/weat/), a weighted gene set enrichment algorithm and online tool by weighting genes using essentiality scores. We confirmed the usefulness of WEAT using three case studies, the functional analysis of one aging-related gene list, one gene list involved in Lung Squamous Cell Carcinoma (LUSC), and one cardiomyopathy gene list from Drosophila model. Finally, we believe that the WEAT method and tool could provide more possibilities for further exploring the functions of given gene lists. AVAILABILITY: The datasets generated and analyzed during the current study are available on our website at https://www.cuilab.cn/weat/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

13.
Acta Pharm Sin B ; 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34002130

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19), which threatens human health and public safety. In the urgent campaign to develop anti-SARS-CoV-2 therapies, the initial entry step is one of the most appealing targets. In this review, we summarize the current understanding of SARS-CoV-2 cell entry, and the development of targeted antiviral strategies. Moreover, we speculate upon future directions toward next-generation of SARS-CoV-2 entry inhibitors during the upcoming post-pandemic era.

14.
Antiviral Res ; 190: 105075, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33872675

RESUMO

The emerging SARS-CoV-2 infection is the cause of the global COVID-19 pandemic. To date, there are limited therapeutic options available to fight this disease. Here we examined the inhibitory abilities of two broad-spectrum antiviral natural products chebulagic acid (CHLA) and punicalagin (PUG) against SARS-CoV-2 viral replication. Both CHLA and PUG reduced virus-induced plaque formation in Vero-E6 monolayer at noncytotoxic concentrations, by targeting the enzymatic activity of viral 3-chymotrypsin-like cysteine protease (3CLpro) as allosteric regulators. Our study demonstrates the potential use of CHLA and PUG as novel COVID-19 therapies.


Assuntos
Antivirais/farmacologia , Benzopiranos/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , SARS-CoV-2/efeitos dos fármacos , Sítio Alostérico , Animais , Antivirais/química , Benzopiranos/química , COVID-19/tratamento farmacológico , COVID-19/virologia , Chlorocebus aethiops , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Descoberta de Drogas , Glucosídeos/química , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , SARS-CoV-2/metabolismo , Células Vero , Replicação Viral/efeitos dos fármacos
15.
Biomed Pharmacother ; 137: 111393, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761610

RESUMO

The leaves of Ficus carica Linn. (FC) have been widely used for medicine purposes since ancient times, and its decoction is consumed as tea. Many scientific papers have been published in the literature and the researchers across the world are still exploring the health benefits of FC leaves. In this review, we have collected the literature published since 2010 in the databases: Pubmed, Scopus, Web of Science, SciFinder, Google Scholar, Baidu Scholar and local classic herbal literature. The summary of the chemical constituents in FC leaves, biological activities, toxicity studies, and clinical studies carried out on FC leaves is provided in this review. In addition, the molecular mechanisms of the active constituents in FC leaves are also comprehended. FC leaves are reported to 126 constituents out of which the polyphenolic compounds are predominant. Many scientific studies have proven the antidiabetic, antioxidant, anti-inflammatory, anticancer, anticholinesterase, antimicrobial, hepatoprotective, and renoprotective activities. Many studies have carried out to provide the insights on molecular pathways involved in the biological activities of FC leaves. The toxicity studies have suggested that FC leaves exhibit toxicity only at very high doses. We believe this review serve as a comprehensive resource for those who are interested to understand the scientific evidence that support the medicinal values of FC leaves and also the research gaps to further improve the commercial value and health benefits of FC leaves.


Assuntos
Ficus/química , Fitoterapia , Folhas de Planta/química , Animais , Etnofarmacologia , Ficus/toxicidade , Humanos , Medicina Tradicional , Folhas de Planta/toxicidade , Plantas Medicinais/química , Plantas Medicinais/toxicidade
16.
Front Cell Dev Biol ; 9: 626047, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33681205

RESUMO

Vascular endothelial cells (VECs) build a barrier separating the blood from the vascular wall. The vascular endothelium is the largest endocrine organ, and is well-known for its crucial role in the regulation of vascular function. The initial response to endothelial cell injury can lead to the activation of VECs. However, excessive activation leads to metabolic pathway disruption, VEC dysfunction, and angiogenesis. The pathways related to VEC metabolic reprogramming recently have been considered as key modulators of VEC function in processes such as angiogenesis, inflammation, and barrier maintenance. In this review, we focus on the changes of VEC metabolism under physiological and pathophysiological conditions.

17.
Nucleic Acids Res ; 49(5): 2522-2536, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33561291

RESUMO

Simultaneous dysregulation of multiple microRNAs (miRs) affects various pathological pathways related to cardiac failure. In addition to being potential cardiac disease-specific markers, miR-23b/27b/24-1 were reported to be responsible for conferring cardiac pathophysiological processes. In this study, we identified a conserved guanine-rich RNA motif within the miR-23b/27b/24-1 cluster that can form an RNA G-quadruplex (rG4) in vitro and in cells. Disruption of this intragenic rG4 significantly increased the production of all three miRs. Conversely, a G4-binding ligand tetrandrine (TET) stabilized the rG4 and suppressed miRs production in human and rodent cardiomyocytes. Our further study showed that the rG4 prevented Drosha-DGCR8 binding and processing of the pri-miR, suppressing the biogenesis of all three miRs. Moreover, CRISPR/Cas9-mediated G4 deletion in the rat genome aberrantly elevated all three miRs in the heart in vivo, leading to cardiac contractile dysfunction. Importantly, loss of the G4 resulted in reduced targets for the aforementioned miRs critical for normal heart function and defects in the L-type Ca2+ channel-ryanodine receptor (LCC-RyR) coupling in cardiomyocytes. Our results reveal a novel mechanism for G4-dependent regulation of miR biogenesis, which is essential for maintaining normal heart function.


Assuntos
Quadruplex G , MicroRNAs/química , MicroRNAs/metabolismo , Contração Miocárdica/genética , Miócitos Cardíacos/metabolismo , Animais , Benzilisoquinolinas/farmacologia , Sistemas CRISPR-Cas , Células Cultivadas , Quadruplex G/efeitos dos fármacos , Regulação da Expressão Gênica , Miocárdio/metabolismo , Miócitos Cardíacos/fisiologia , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/metabolismo , Ratos , Ratos Sprague-Dawley , Ribonuclease III/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo
18.
Br J Pharmacol ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33555034

RESUMO

BACKGROUND AND PURPOSE: Ageing is associated with progressive metabolic dysregulation. Rutin is a metabolic regulator with a poor solubility. Using soluble sodium rutin we investigating the effect and mechanisms of rutin in ageing process. EXPERIMENTAL APPROACH: Wild type male mice were treated with or without sodium rutin ( 0.2 mg·ml-1 in drinking water from 8-month-old until end of life. Kaplan-Meier survival curve was used for lifespan assay, ageing-related histopathology analysis and metabolic analysis were performed to determine the effects of chronic sodium rutin on the longevity. Serological test, liver tissue metabolomics and transcriptomics were used for liver function assay. SiRNA knockdown Angptl8 and autophagy flux assay in HepG2 cell lines explored the mechanism through which sodium rutin might impact the function of hepatocyte. KEY RESULTS: Sodium rutin treatment extends the lifespan of mice by 10%. Sodium rutin supplementation alleviates ageing-related pathological changes and promotes behaviour performance in ageing mice. Sodium rutin supplementation altered the whole-body metabolism in mice, which exhibited increased energy expenditure and lower respiratory quotient. Transcriptomics analysis showed that Sodium rutin affected the expression of metabolic genes. Metabolomics analysis showed that Sodium rutin reduced liver steatosis through increased lipid ß-oxidation. Sodium rutin treatment increased the autophagy level both in vivo and in vitro. The inhibition of autophagy partially abolished the sodium rutin-mediated effect on lipolysis in HepG2 cells. CONCLUSION AND IMPLICATIONS: Sodium rutin treatment extends the lifespan and health span of mice with beneficial effects on metabolism, which were achieved by enhancing the autophagy activity in hepatocytes.

19.
Cell Biosci ; 11(1): 45, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33640032

RESUMO

BACKGROUND: In the urgent campaign to develop therapeutics against SARS-CoV-2, natural products have been an important source of new lead compounds. RESULTS: We herein identified two natural products, ginkgolic acid and anacardic acid, as inhibitors using a high-throughput screen targeting the SARS-CoV-2 papain-like protease (PLpro). Moreover, our study demonstrated that the two hit compounds are dual inhibitors targeting the SARS-CoV-2 3-chymotrypsin-like protease (3CLpro) in addition to PLpro. A mechanism of action study using enzyme kinetics further characterized the two compounds as irreversible inhibitors against both 3CLpro and PLpro. Significantly, both identified compounds inhibit SARS-CoV-2 replication in vitro at nontoxic concentrations. CONCLUSIONS: Our finding provides two novel natural products as promising SARS-CoV-2 antivirals.

20.
Sci Rep ; 11(1): 3469, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568719

RESUMO

Most current circulating miRNA biomarkers are derived from peripheral venous blood, whereas miRNA deregulation in arterial blood in disease conditions has been largely ignored. To explore whether peripheral venous blood miRNAs could represent a bona fide specific miRNA deregulation pattern, we selected hypertension, a disease that is particularly associated with vessels, as the model. Circulating miRNA profiles of arterial and venous blood from spontaneously hypertensive (SHR) rats and their corresponding controls (i.e., WKY rats) were investigated by next-generation miRNA sequencing. Little miRNAs were observed between arterial and venous circulating miRNAs in WKY rats. Interestingly, this number was enhanced in SHR hypertensive rats. Bioinformatical analysis of disease association, enriched target genes and the regulatory transcription factors of these differentially expressed miRNAs implied a potential functional link with cardiovascular disease-related functions. Comparisons between arterial and venous miRNAs in hypertension-versus-control conditions also revealed prominent disease association of circulating miRNAs and their target genes in arteries but not in veins. Moreover, a young non-hypertensive animal model in SHR background (i.e. JSHR) was used as a second control for SHR. Additional transcriptomic analysis and droplet digital PCR validation of arterial and venous deregulated miRNAs among SHR and its two controls (WKY, JSHR) revealed a noticeable consensus of artery-deregulated miRNAs in hypertension and two novel arterial circulating signatures (miR-455-3p and miR-140-3p) of hypertension. These results suggest the necessity of re-evaluating the efficacy of certain venous miRNAs identified in previous studies as potential biomarkers in cardiovascular diseases or a wider disease spectrum.


Assuntos
MicroRNA Circulante/sangue , Perfilação da Expressão Gênica , Hipertensão/sangue , Animais , Artérias , Biomarcadores/sangue , Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Hipertensão/genética , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Veias
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