Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarke...Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.展开更多
Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototox...Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.展开更多
BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the ...BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.展开更多
铁死亡是近年来新发现的一种程序性细胞死亡形式,以铁依赖性氧化损伤、脂质过氧化和活性氧(reactive oxygen species,ROS)积累为特征,现成为缺血再灌注损伤(ischemia and reperfusion,I/R)、心血管疾病、肿瘤和神经系统疾病领域的重要...铁死亡是近年来新发现的一种程序性细胞死亡形式,以铁依赖性氧化损伤、脂质过氧化和活性氧(reactive oxygen species,ROS)积累为特征,现成为缺血再灌注损伤(ischemia and reperfusion,I/R)、心血管疾病、肿瘤和神经系统疾病领域的重要研究课题。展开更多
Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with...Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.展开更多
microRNAs (miRNAs)是一类通常存在于细胞质中的短链非编码RNAs,通过与信使RNA (mRNA)的3'非翻译区(3'untranslated region, 3'UTR)结合,发挥调节转录后基因表达的功能。miRNAs在调控多种代谢过程和信号转导途径方面起着重...microRNAs (miRNAs)是一类通常存在于细胞质中的短链非编码RNAs,通过与信使RNA (mRNA)的3'非翻译区(3'untranslated region, 3'UTR)结合,发挥调节转录后基因表达的功能。miRNAs在调控多种代谢过程和信号转导途径方面起着重要作用。线粒体是真核细胞中进行氧化代谢和ATP合成的关键场所,负责糖类、脂质和氨基酸等大分子的代谢。那些特异性定位于线粒体的miRNAs,以及在细胞质中直接或间接调节线粒体特定功能的miRNAs,被称为线粒体miRNAs (mitochondrial miRNAs, mitomiRs)。这些miRNAs能调控相关基因表达,并在关键线粒体代谢途径中发挥独特作用,从而促进肿瘤的发生与发展。本文重点探讨mitomiR在线粒体中的作用以及在肿瘤中的调控机制,旨在进一步阐明肿瘤发生发展的分子机制,开发潜在的癌症新疗法。microRNAs (miRNAs) are a class of short non-coding RNAs typically found in the cytoplasm. They function to regulate post-transcriptional gene expression by binding to the 3' untranslated region (3'UTR) of messenger RNA (mRNA). miRNAs play a crucial role in modulating various metabolic processes and signal transduction pathways. Mitochondria serve as the primary sites for oxidative metabolism and ATP synthesis in eukaryotic cells, and they are responsible for the metabolism of macromolecules, including sugars, lipids, and amino acids. Mitochondrial miRNAs (mitomiRs) are a subset of miRNAs localized specifically within mitochondria and modulate mitochondrial-specific functions, either directly or indirectly, within the cytoplasm. These mitomiRs can modulate gene expression and have a distinct role in pivotal mitochondrial metabolic pathways, thereby influencing the initiation and progression of tumors. This article concentrates on the role of mitomiRs in mitochondria and their regulatory mechanisms in tumorigenesis, with the goal of further elucidating the molecular underpinnings of tumorigenesis and development, and of identifying potential novel therapeutic targets for cancer.展开更多
BACKGROUND India has the highest tuberculosis(TB)burden in the world.Of the estimated annual 10 million TB cases,features of extra pulmonary TB are evident in up to 45%.Urogenital TB(UGTB)accounts for approximately 20...BACKGROUND India has the highest tuberculosis(TB)burden in the world.Of the estimated annual 10 million TB cases,features of extra pulmonary TB are evident in up to 45%.Urogenital TB(UGTB)accounts for approximately 20%of those cases.The lack of non-sputum based diagnostic tools continue to hinder efforts to reduce the burden of UGTB.MicroRNAs(miRNAs)play a crucial role in biological pathways and can be used as a potential biomarker for TB.We evaluated urinary extracellular vesicles(uEVs)as non-invasive source to explore miRNAs with biomarker potential for UGTB.AIM To evaluate the potential of miRNA-155-5p,miRNA-26a-5p and miRNA-29a-3p in uEVs to diagnose UGTB in adults.METHODS uEV characterization was done using nanoparticle tracking analysis and flow cytometry.Quantitative reverse transcriptase polymerase chain reaction(qRTPCR)for urinary uEV-miRNAs were carried out in samples from patients with suspected UGTB,or Urinary tract infections[UTI,disease controls(DC)]and healthy controls(HCs)(n=20/group).U6 was used to normalize the qRT-PCR data.Receivers operating characteristic curves was used to calculate the diagnostic accuracy of uEV-miRNAs to differentiate UGTB from controls(DC and HCs).RESULTS uEVs from UGTB or UTI patients had higher mean size,and also lower proportion of CD63 positive vesicles as compared to HC’s uEVs.Between UTI and UGTB,the mean size of uEVs was significantly higher in UTI cases.qRT-PCR analysis revealed a significantly lower abundance of miRNA-155-5p and miRNA-26a-5p in uEVs from UGTB relative to UTI(P value=0.004)and HC(P value=0.009)respectively n=20/group).While,miRNA-29a-3p was higher in abundance in both UGTB and HCs’uEV,relative to uEVs from UTI cases(P values=0.004 and 0.002 respectively,n=20/group).Moreover,miRNA-155-5p[area under curve(AUC)=0.88,P≤0.0001]and miRNA-29a-3p(AUC=0.76,P value=0.005)had optimal diagnostic accuracy to differentiate UGTB from DC(n=20/groups)with a likelihood ratio of 5.2 and 4.3,respectively through receivers operating characteristic curve.While,miRNA-155-5p(AUC=0.68,P value=0.05)and miRNA-26a-5p(AUC=0.78,P value=0.002)had optimal diagnostic accuracy to differentiate UGTB from HCs with a likelihood ratio of>2.CONCLUSION The differential expression of uEV-miRNAs,miRNA-155-5p and miRNA-29a-3p in UTGB and UTI cases hold promise in the specific diagnosis of UGTB.Further studies in large cohort are,however,needed to confirm the diagnostic accuracy of these uEV-miRNAs.展开更多
MicroRNAs(miRNAs)are a class of single-stranded and non-coding endogenous RNAs with 18−25 nucleotides in length.By binding to the complementary sequences in the 3′-untranslated region(3′-UTR)of protein coding genes,...MicroRNAs(miRNAs)are a class of single-stranded and non-coding endogenous RNAs with 18−25 nucleotides in length.By binding to the complementary sequences in the 3′-untranslated region(3′-UTR)of protein coding genes,miRNAs regulate posttranscriptionally the mRNA expression of target genes and enzymes involved in various biological processes.The application of high-throughput sequencing,bioinformatics analysis,and novel detection methods has high-lighted promising roles of miRNAs as both novel biomarkers for tumor diagnosis and critical regulators involved in almost all stages of carcinogenesis including cancer initiation,promotion and progression.Epigallocatechin-3-gallate(EGCG),the most investigated active catechin in green tea,has been linked to various health-promoting benefits including chemoprevention and treatment of cancers.In this review,we first present a brief description of EGCG and its major metabolic pathway.It is followed by reviewing the roles of EGCG in the modulation of oncogenic and tumor suppressing miRNAs in some common cancers.These findings suggest that the capacity of EGCG to regulate expression of specific miRNAs provides insights of its new mechanisms of action underlying its chemopreventive and potential beneficial activities against various cancers.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimall...BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimally invasive biomarkers need to be integrated into clinical practice.AIM To identify circulating microRNAs as potential CRC biomarkers through a com-parative analysis of tissue and plasma samples from patients with CRC.METHODS This case-control study conducted a quantitative real-time polymerase chain reaction analysis of 84 microRNAs in tumoral and peritumoral tissues,and 179 microRNAs in plasma from 19 patients with CRC.A control cohort for the tissue analysis and another control cohort for the plasma analysis have been enrolled.RESULTS In total,14 microRNAs were significantly differentially expressed in the tissue and plasma samples.Notably,five microRNAs(miR-26b-5p,miR-101-3p,miR-30d-5p,miR-107,and miR-21-5p)presented the same trend in terms of fold change in both types of biological samples.Significant associations between the circulating levels of miR-21-5p and miR-26b-5p and lymphovascular invasion were found.CONCLUSION These five microRNAs with significantly altered levels in plasma and tumoral tissue,could be good non-invasive CRC biomarkers candidates,enhancing screening,and supporting precision and individualized patient care.展开更多
MicroRNAs(miRNAs)are abundant in the brain and mounting evidence suggests their involvement in the critical processes such as neurodevelopment,synaptic plasticity,and the development of neurodegenerative diseases.Thus...MicroRNAs(miRNAs)are abundant in the brain and mounting evidence suggests their involvement in the critical processes such as neurodevelopment,synaptic plasticity,and the development of neurodegenerative diseases.Thus,miRNAs may be promising therapeutic drugs for the treatment of neurodegenerative disorders.However,naked miRNAs are not able to enter cells directly,especially brain cells.Therefore,suitable carriers for safe and efficient miRNA delivery to brain cells are of great importance.Chitosan nanoparticles,with the excellent properties such as good compatibility and brilliant degradability,may act as a promising carrier for miRNA drug delivery.In this study,chitosan nanoparticles were prepared and their properties such as particle size,zeta potential and encapsulation efficiency were optimized to encapsulate miRNAs.The delivery efficiency of miRNA-loaded nanoparticles was then evaluated in both neuronal and microglia cells.The results demonstrated chitosan nanoparticles encapsulated miRNAs efficiently and showed excellent sustained releasing in vitro.Moreover,chitosan nanoparticles delivered miRNA to both neurons and microglia with very low toxicity and high efficiency.In conclusion,chitosan nanoparticles are promising carriers for the delivery of miRNAs to brain cells,which may be used for the early intervention and treatment of neurodegenerative disorders.展开更多
MicroRNAs(miRNAs)are small non-coding RNAs of 20-22 nucleotides in length.They have been identified as major regulators in the secretome of mesenchymal stem cells(MSCs)including adipose tissue,bone marrow,Wharton’s j...MicroRNAs(miRNAs)are small non-coding RNAs of 20-22 nucleotides in length.They have been identified as major regulators in the secretome of mesenchymal stem cells(MSCs)including adipose tissue,bone marrow,Wharton’s jelly,and dental pulp.These MSCs and their secretome with specific miRNAs are known modulators of the immune response,angiogenesis,inflammation,and apoptosis.In this review,the application of MSC-derived miRNAs in treating several ocular conditions including dry eye,glaucoma,and retinal degenerative diseases has been compiled.In addition,the emerging role of MSC-derived extracellular vesicles carrying miRNAs as a major cargo,regulating the target cells in the human eye has been reviewed.Finally,the bioengineering of nanovesicles with specific MSC-derived miRNAs as novel drug therapy has been discussed.展开更多
Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and in...Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc.展开更多
文摘Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of bipolar disorder. We performed a PubMed search for microRNA biomarkers in bipolar disorder and found 18 original research articles on studies performed with human patients and published from January 2011 to June 2023. These studies included microRNA profiling in bloodand brain-based materials. From the studies that had validated the preliminary findings,potential candidate biomarkers for bipolar disorder in adults could be miR-140-3p,-30d-5p,-330-5p,-378a-5p,-21-3p,-330-3p,-345-5p in whole blood, miR-19b-3p,-1180-3p,-125a-5p, let-7e-5p in blood plasma, and miR-7-5p,-23b-5p,-142-3p,-221-5p,-370-3p in the blood serum. Two of the studies had investigated the changes in microRNA expression of patients with bipolar disorder receiving treatment. One showed a significant increase in plasma miR-134 compared to baseline after 4 weeks of treatment which included typical antipsychotics, atypical antipsychotics, and benzodiazepines. The other study had assessed the effects of prescribed medications which included neurotransmitter receptorsite binders(drug class B) and sedatives, hypnotics, anticonvulsants, and analgesics(drug class C) on microRNA results. The combined effects of the two drug classes increased the significance of the results for miR-219 and-29c with miR-30e-3p and-526b* acquiring significance. MicroRNAs were tested to see if they could serve as biomarkers of bipolar disorder at different clinical states of mania, depression, and euthymia. One study showed that upregulation in whole blood of miR-9-5p,-29a-3p,-106a-5p,-106b-5p,-107,-125a-3p,-125b-5p and of miR-107,-125a-3p occurred in manic and euthymic patients compared to controls, respectively, and that upregulation of miR-106a-5p,-107 was found for manic compared to euthymic patients. In two other studies using blood plasma,downregulation of miR-134 was observed in manic patients compared to controls, and dysregulation of miR-134,-152,-607,-633,-652,-155 occurred in euthymic patients compared to controls. Finally, microRNAs such as miR-34a,-34b,-34c,-137, and-140-3p,-21-3p,-30d-5p,-330-5p,-378a-5p,-134,-19b-3p were shown to have diagnostic potential in distinguishing bipolar disorder patients from schizophrenia or major depressive disorder patients, respectively. Further studies are warranted with adolescents and young adults having bipolar disorder and consideration should be given to using animal models of the disorder to investigate the effects of suppressing or overexpressing specific microRNAs.
文摘Hearing loss is the third leading cause of human disability.Age-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health burden.Noise-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing loss.The etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental factors.Oxidative stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing loss.Short non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic response.Sensory hair cell death is a central histopathological finding in sensorineural hearing loss.As these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing loss.Ovid EMBASE,Ovid MEDLINE,Web of Science Core Collection,and ClinicalTrials.gov databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical trials.Registe red clinical trials known to the senior author we re also assessed.A total of 222studies were thus identified.After excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text screening.This resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative review.MiRNAs miR-34a and miR-29b levels increase with age in mice.These miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT1p53,and SIRT1/hypoxia-inducible factor 1-alpha signaling pathways resulting in increased apoptosis.Furthermore,hypoxia and oxidative stress had a similar adve rse apoptotic effect,which was inhibited by resve ratrol and a myocardial inhibitorassociated transcript,a miR-29b competing endogenous mRNA.Gentamicin reduced miR-182-5p levels and increased cochlear oxidative stress and cell death in mice-an effect that was corrected by inner ear stem cell-derived exosomes.There is ongoing work seeking to determine if these findings can be effectively translated to humans.
基金Supported by Patronage of the Autonomous University of Nayarit,Quality Postgraduate Program with resources from the 15%Special Tax allocated to the UAN 2022.
文摘BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.
文摘Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.
文摘microRNAs (miRNAs)是一类通常存在于细胞质中的短链非编码RNAs,通过与信使RNA (mRNA)的3'非翻译区(3'untranslated region, 3'UTR)结合,发挥调节转录后基因表达的功能。miRNAs在调控多种代谢过程和信号转导途径方面起着重要作用。线粒体是真核细胞中进行氧化代谢和ATP合成的关键场所,负责糖类、脂质和氨基酸等大分子的代谢。那些特异性定位于线粒体的miRNAs,以及在细胞质中直接或间接调节线粒体特定功能的miRNAs,被称为线粒体miRNAs (mitochondrial miRNAs, mitomiRs)。这些miRNAs能调控相关基因表达,并在关键线粒体代谢途径中发挥独特作用,从而促进肿瘤的发生与发展。本文重点探讨mitomiR在线粒体中的作用以及在肿瘤中的调控机制,旨在进一步阐明肿瘤发生发展的分子机制,开发潜在的癌症新疗法。microRNAs (miRNAs) are a class of short non-coding RNAs typically found in the cytoplasm. They function to regulate post-transcriptional gene expression by binding to the 3' untranslated region (3'UTR) of messenger RNA (mRNA). miRNAs play a crucial role in modulating various metabolic processes and signal transduction pathways. Mitochondria serve as the primary sites for oxidative metabolism and ATP synthesis in eukaryotic cells, and they are responsible for the metabolism of macromolecules, including sugars, lipids, and amino acids. Mitochondrial miRNAs (mitomiRs) are a subset of miRNAs localized specifically within mitochondria and modulate mitochondrial-specific functions, either directly or indirectly, within the cytoplasm. These mitomiRs can modulate gene expression and have a distinct role in pivotal mitochondrial metabolic pathways, thereby influencing the initiation and progression of tumors. This article concentrates on the role of mitomiRs in mitochondria and their regulatory mechanisms in tumorigenesis, with the goal of further elucidating the molecular underpinnings of tumorigenesis and development, and of identifying potential novel therapeutic targets for cancer.
基金Supported by the Indian Council of Medical Research,No.Coord/7(1)/CARE-KD/18-NCD-II.
文摘BACKGROUND India has the highest tuberculosis(TB)burden in the world.Of the estimated annual 10 million TB cases,features of extra pulmonary TB are evident in up to 45%.Urogenital TB(UGTB)accounts for approximately 20%of those cases.The lack of non-sputum based diagnostic tools continue to hinder efforts to reduce the burden of UGTB.MicroRNAs(miRNAs)play a crucial role in biological pathways and can be used as a potential biomarker for TB.We evaluated urinary extracellular vesicles(uEVs)as non-invasive source to explore miRNAs with biomarker potential for UGTB.AIM To evaluate the potential of miRNA-155-5p,miRNA-26a-5p and miRNA-29a-3p in uEVs to diagnose UGTB in adults.METHODS uEV characterization was done using nanoparticle tracking analysis and flow cytometry.Quantitative reverse transcriptase polymerase chain reaction(qRTPCR)for urinary uEV-miRNAs were carried out in samples from patients with suspected UGTB,or Urinary tract infections[UTI,disease controls(DC)]and healthy controls(HCs)(n=20/group).U6 was used to normalize the qRT-PCR data.Receivers operating characteristic curves was used to calculate the diagnostic accuracy of uEV-miRNAs to differentiate UGTB from controls(DC and HCs).RESULTS uEVs from UGTB or UTI patients had higher mean size,and also lower proportion of CD63 positive vesicles as compared to HC’s uEVs.Between UTI and UGTB,the mean size of uEVs was significantly higher in UTI cases.qRT-PCR analysis revealed a significantly lower abundance of miRNA-155-5p and miRNA-26a-5p in uEVs from UGTB relative to UTI(P value=0.004)and HC(P value=0.009)respectively n=20/group).While,miRNA-29a-3p was higher in abundance in both UGTB and HCs’uEV,relative to uEVs from UTI cases(P values=0.004 and 0.002 respectively,n=20/group).Moreover,miRNA-155-5p[area under curve(AUC)=0.88,P≤0.0001]and miRNA-29a-3p(AUC=0.76,P value=0.005)had optimal diagnostic accuracy to differentiate UGTB from DC(n=20/groups)with a likelihood ratio of 5.2 and 4.3,respectively through receivers operating characteristic curve.While,miRNA-155-5p(AUC=0.68,P value=0.05)and miRNA-26a-5p(AUC=0.78,P value=0.002)had optimal diagnostic accuracy to differentiate UGTB from HCs with a likelihood ratio of>2.CONCLUSION The differential expression of uEV-miRNAs,miRNA-155-5p and miRNA-29a-3p in UTGB and UTI cases hold promise in the specific diagnosis of UGTB.Further studies in large cohort are,however,needed to confirm the diagnostic accuracy of these uEV-miRNAs.
基金supported by Shandong Provincial Natural Science Foundation(ZR2022MC004)the Project of Key Research and Development Program of Shandong Province(2021TZXD007,2023TZXD070).
文摘MicroRNAs(miRNAs)are a class of single-stranded and non-coding endogenous RNAs with 18−25 nucleotides in length.By binding to the complementary sequences in the 3′-untranslated region(3′-UTR)of protein coding genes,miRNAs regulate posttranscriptionally the mRNA expression of target genes and enzymes involved in various biological processes.The application of high-throughput sequencing,bioinformatics analysis,and novel detection methods has high-lighted promising roles of miRNAs as both novel biomarkers for tumor diagnosis and critical regulators involved in almost all stages of carcinogenesis including cancer initiation,promotion and progression.Epigallocatechin-3-gallate(EGCG),the most investigated active catechin in green tea,has been linked to various health-promoting benefits including chemoprevention and treatment of cancers.In this review,we first present a brief description of EGCG and its major metabolic pathway.It is followed by reviewing the roles of EGCG in the modulation of oncogenic and tumor suppressing miRNAs in some common cancers.These findings suggest that the capacity of EGCG to regulate expression of specific miRNAs provides insights of its new mechanisms of action underlying its chemopreventive and potential beneficial activities against various cancers.
基金Supported by European Union’s NextGeneration PNRR-III-C9-2022-I5,managed by the Ministry of Research,Innovation and Digitization,No.760009/30.12.2022,code CF 14/16.11.2022Ministry of Research,Innovation and Digitization of Romania,No.PN 23.16.02.04.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most common cancers worldwide.The gold standard screening methods for early detection and monitoring are colonoscopy and stool-based tests.However,innovative and minimally invasive biomarkers need to be integrated into clinical practice.AIM To identify circulating microRNAs as potential CRC biomarkers through a com-parative analysis of tissue and plasma samples from patients with CRC.METHODS This case-control study conducted a quantitative real-time polymerase chain reaction analysis of 84 microRNAs in tumoral and peritumoral tissues,and 179 microRNAs in plasma from 19 patients with CRC.A control cohort for the tissue analysis and another control cohort for the plasma analysis have been enrolled.RESULTS In total,14 microRNAs were significantly differentially expressed in the tissue and plasma samples.Notably,five microRNAs(miR-26b-5p,miR-101-3p,miR-30d-5p,miR-107,and miR-21-5p)presented the same trend in terms of fold change in both types of biological samples.Significant associations between the circulating levels of miR-21-5p and miR-26b-5p and lymphovascular invasion were found.CONCLUSION These five microRNAs with significantly altered levels in plasma and tumoral tissue,could be good non-invasive CRC biomarkers candidates,enhancing screening,and supporting precision and individualized patient care.
基金supported financially by the NSFC(Nos.62075098 and 62071119)the National Key Research and Development Program of China(Nos.2017YFA0205301 and 2018YFC1602905)。
文摘MicroRNAs(miRNAs)are abundant in the brain and mounting evidence suggests their involvement in the critical processes such as neurodevelopment,synaptic plasticity,and the development of neurodegenerative diseases.Thus,miRNAs may be promising therapeutic drugs for the treatment of neurodegenerative disorders.However,naked miRNAs are not able to enter cells directly,especially brain cells.Therefore,suitable carriers for safe and efficient miRNA delivery to brain cells are of great importance.Chitosan nanoparticles,with the excellent properties such as good compatibility and brilliant degradability,may act as a promising carrier for miRNA drug delivery.In this study,chitosan nanoparticles were prepared and their properties such as particle size,zeta potential and encapsulation efficiency were optimized to encapsulate miRNAs.The delivery efficiency of miRNA-loaded nanoparticles was then evaluated in both neuronal and microglia cells.The results demonstrated chitosan nanoparticles encapsulated miRNAs efficiently and showed excellent sustained releasing in vitro.Moreover,chitosan nanoparticles delivered miRNA to both neurons and microglia with very low toxicity and high efficiency.In conclusion,chitosan nanoparticles are promising carriers for the delivery of miRNAs to brain cells,which may be used for the early intervention and treatment of neurodegenerative disorders.
文摘MicroRNAs(miRNAs)are small non-coding RNAs of 20-22 nucleotides in length.They have been identified as major regulators in the secretome of mesenchymal stem cells(MSCs)including adipose tissue,bone marrow,Wharton’s jelly,and dental pulp.These MSCs and their secretome with specific miRNAs are known modulators of the immune response,angiogenesis,inflammation,and apoptosis.In this review,the application of MSC-derived miRNAs in treating several ocular conditions including dry eye,glaucoma,and retinal degenerative diseases has been compiled.In addition,the emerging role of MSC-derived extracellular vesicles carrying miRNAs as a major cargo,regulating the target cells in the human eye has been reviewed.Finally,the bioengineering of nanovesicles with specific MSC-derived miRNAs as novel drug therapy has been discussed.
基金Supported by 2024 Yeungnam University Grant,No.224A480005.
文摘Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc.
