Non-coding RNAs in acute ischemic stroke:from brain to periphery

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

Long non-coding RNAs with essential roles in neurodegenerative disorders

Recently,with the advent of high-resolution and high-throughput sequencing technologies,an increasing number of long non-coding RNAs(lncRNAs)have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns,across different neurodegenerative diseases.However,the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood.This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles,regulatory mechanisms,and research status of lncRNAs in Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis.Finally,this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases,hoping to provide broader implications for developing effective treatments.

Characterization of N6-methyladenosine long non-coding RNAs in sporadic congenital cataract and age-related cataract

AIM:To characterize the N6-methyladenosine(m6A)modification patterns in long non-coding RNAs(lncRNAs)in sporadic congenital cataract(CC)and age-related cataract(ARC).METHODS:Anterior capsule of the lens were collected from patients with CC and ARC.Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs.RESULTS:Large amount of m6A peaks within lncRNA were identified for both CC and ARC,while the level was much higher in ARC(49870 peaks)than that in CC(18688 peaks),yet those difference between ARC in younger age group(ARC-1)and ARC in elder age group(ARC-2)was quite slight.A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs,as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC.On the other hand,5893 hypermethylated and 5213 hypomethylated lncRNAs,as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1.Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles,as well as nucleotide excision repair.CONCLUSION:Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC,providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

Navigating the labyrinth of long non-coding RNAs in colorectal cancer:From chemoresistance to autophagy

Long non-coding RNAs(lncRNAs),with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity,have been found to impact colorectal cancer(CRC)through various biological processes.LncRNA expression can regulate autophagy,which plays dual roles in the initiation and progression of cancers,including CRC.Abnormal expression of lncRNAs is associated with the emergence of chemoresistance.Moreover,it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance.Two recent studies titled“Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506”and“Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription”revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC,respectively.In this editorial,we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.

Construction of prognostic markers for gastric cancer and comprehensive analysis of pyroptosis-related long non-coding RNAs

BACKGROUND China's most frequent malignancy is gastric cancer(GC),which has a very poor survival rate,and the survival rate for patients with advanced GC is dismal.Pyroptosis has been connected to the genesis and development of cancer.The function of pyroptosis-related long non-coding RNAs(PRLs)in GC,on the other hand,remains uncertain.AIM To explore the construction and comprehensive analysis of the prognostic characteristics of long non-coding RNA(lncRNA)related to pyroptosis in GC patients.METHODS The TCGA database provided us with 352 stomach adenocarcinoma samples,and we obtained 28 pyroptotic genes from the Reactome database.We examined the correlation between lncRNAs and pyroptosis using the Pearson correlation coefficient.Prognosis-related PRLs were identified through univariate Cox analysis.A predictive signature was constructed using stepwise Cox regression analysis,and its reliability and independence were assessed.To facilitate clinical application,a nomogram was created based on this signature.we analyzed differences in immune cell infiltration,immune function,and checkpoints between the high-risk group(HRG)and low-risk group(LRG).RESULTS Five hundred and twenty-three PRLs were screened from all lncRNAs(absolute correlation coefficient>0.4,P<0.05).Nine PRLs were included in the risk prediction signature that was created through stepwise Cox regression analysis.We determined the risk score for GC patients and employed the median value as the dividing line between HRG and LRG.The ability of the risk signature to predict the overall survival(OS)of GC is demonstrated by the Kaplan-Meier analysis,risk curve,receiver operating characteristic curve,and decision curve analysis curve.The risk signature was shown to be an independent prognostic factor for OS in both univariate and multivariate Cox regression analyses.HRG showed a more efficient local immune response or modulation compared to LRG,as indicated by the predicted signal pathway analysis and examination of immune cell infiltration,function,and checkpoints(P<0.05).CONCLUSION In general,we have created a brand-new prognostic signature using PRLs,which may provide ideas for immunotherapy in patients with GC.

Clinical application value of long non-coding RNAs signatures of genomic instability in predicting prognosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)presents challenges due to its high recurrence and metastasis rates and poor prognosis.While current clinical diagnostic and prognostic indicators exist,their accuracy remains imperfect due to their biol-ogical complexity.Therefore,there is a quest to identify improved biomarkers for HCC diagnosis and prognosis.By combining long non-coding RNA(lncRNA)expression and somatic mutations,Duan et al identified five representative lncRNAs from 88 lncRNAs related to genomic instability(GI),forming a GI-derived lncRNA signature(LncSig).This signature outperforms previously re-ported LncSig and TP53 mutations in predicting HCC prognosis.In this editorial,we comprehensively evaluate the clinical application value of such prognostic evaluation model based on sequencing technology in terms of cost,time,and practicability.Additionally,we provide an overview of various prognostic models for HCC,aiding in a comprehensive understanding of research progress in pro-gnostic evaluation methods.

Role of long non-coding RNAs in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.

Non-coding RNAs:The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury

Hepatic ischemia-reperfusion injury(HIRI)is the major complication of liver surgery and liver transplantation,that may increase the postoperative morbidity,mortality,tumor progression,and metastasis.The underlying mechanisms have been extensively investigated in recent years.Among these,oxidative stress,inflammatory responses,immunoreactions,and cell death are the most studied.Non-coding RNAs(ncRNAs)are defined as the RNAs that do not encode proteins,but can regulate gene expressions.In recent years,ncRNAs have emerged as research hotspots for various diseases.During the progression of HIRI,ncRNAs are differentially expressed,while these dysregulations of ncRNAs,in turn,have been verified to be related to the above pathological processes involved in HIRI.ncRNAs mainly contain microRNAs,long ncRNAs,and circular RNAs,some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity,and as therapeutic targets to attenuate HIRI.Here,we briefly summarize the common pathophysiology of HIRI,describe the current knowledge of ncRNAs involved in HIRI in animal and human studies,and discuss the potential of ncRNA-targeted therapeutic strategies.Given the scarcity of clinical trials,there is still a long way to go from pre-clinical to clinical application,and further studies are needed to uncover their potential as therapeutic targets.

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential

Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs(ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation,and by epigenetic modification.In this review,we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin.Furthermore,we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy.This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

Identification and Characterization of Long Non-Coding RNAs Involved in Sex-Related Gene Regulation in Kelp Saccharina japonica

Long non-coding RNAs(lncRNAs)regulate a variety of biological processes,including sexual reproduction and differentiation.Saccharina japonica,a commercially important brown alga in China,shows remarkable sexual dimorphism in haploid gametophytes.The sex of Saccharina japonica gametophytes is determined by UV sexual system.However,no results have been reported on the lncRNAs involved in the sex-related gene regulation of S.japonica.This study identified a number of lncRNAs and assessed their expression levels in male and female gametophytes.Among them,a total of 405 lncRNAs and 211 mRNAs showed differential expressions.Furthermore,the functions of target genes of differentially expressed lncRNAs(DELs)differed from those of differentially expressed genes(DEGs),suggesting that lncRNA may interact with other functional proteins,in addition to DEGs,to involve sex regulation in S.japonica.There were 32 and 90 potential cis-regulatory and trans-regulatory interactions between DELsDEGs,respectively.Five of these lncRNAs(LNC_002974,LNC_021059,LNC_038466,LNC_051584,and LNC_027400)interacted with putative male sex determination region(SDR)genes,suggesting that they act as regulators in gametophytes'sex regulation potentially.Findings from this study contribute to our understanding of the roles of lncRNAs in sex differentiation and lay the foundation for functional studies of candidate lncRNAs in the future.

Non-coding RNAs:an emerging player in osteomyelitis

Osteomyelitis is a debilitating bone infection primarily caused by Staphylococcus aureus.Despite advancements in surgery and chemotherapy,the treatment of osteomyelitis remains unsatisfactory,characterized by antibiotic resistance and recurrent relapses.Numerous studies have confirmed that non-coding RNAs could play an emerging role in regulating gene expression,as well as in the differentiation of osteoblasts and osteoclasts,along with bone formation.In this context,we provide an overview of current knowledge regarding the roles of non-coding RNAs in osteomyelitis and explore the potential therapeutic applications of these molecules in disease management,aiming to uncover novel diagnostic and treatment approaches.

Molecular hallmarks of long non-coding RNAs in aging and its significant effect on aging-associated diseases

Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.

Involvement of long non-coding RNAs in pear fruit senescence under high-and low-temperature conditions

Pear fruit senescence under high-and low-temperature conditions has been reported to be mediated by microRNAs.Long non-coding RNAs(lncRNAs),which can function as competing endogenous RNAs that interact with microRNAs,may also be involved in temperature-affected fruit senescence.Based on the transcriptome and microRNA sequencings,in this study,3330 lncRNAs were isolated from Pyrus pyrifolia fruit.Of these lncRNAs,2060 and 537 were responsive to high-and low-temperature conditions,respectively.Of these differentially expressed lncRNAs,82 and 24 correlated to the mRNAs involved in fruit senescence under high-and low-temperature conditions,respectively.Moreover,three lncRNAs were predicted to be competing endogenous RNAs(ceRNAs)that interact with the microRNAs involved in fruit senescence,while one and two ceRNAs were involved in fruit senescence under high-and low-temperature conditions,respectively.A dual-luciferase assay showed that the interaction of an lncRNA with a microRNA disrupts the action of the microRNA on the expression of its target mRNA(s).Furthermore,four alternative splicing-derived lncRNAs interacted with miR172i homologies(Novel_88 and Novel_69)to relieve the repressed expression of their target and produce an miR172i precursor.Correlation analysis of microRNA expression suggested that Novel_69 is likely involved in the cleavage of the pre-miR172i hairpin to generate mature miR172i.Taken together,lncRNAs are involved in pear fruit senescence under high-or low-temperature conditions through ceRNAs and the production of microRNA.

The Dual Role of Non-coding RNAs in the Development of Periodontitis

This review aims to sum up how Non-coding RNAs(ncRNAs)regulate the development of periodontitis and provides a new perspective for understanding the pathogenesis of periodontitis.We explored the ncRNA's dual role in the development of periodontitis by summarizing evidence from previous in vivo and in vitro studies as well as clinical samples.In our review,the downregulation of 18 miRNAs,22 lncRNAs and 10 circRNAs demonstrates protective roles in periodontitis.In contrast,the expression of other 11 miRNAs,7 lncRNAs and 6 circRNAs are upregulated in periodontitis,which promote the progression of periodontitis.These dysregulated ncRNAs exert their protective or destructive roles by mainly influencing cell proliferation,differentiation and apoptosis via cross-talking with various molecules or signaling pathways.Our findings suggested which and how ncRNAs promote or delay the progression of periodontitis,which may greatly contribute to diagnose and therapy development of periodontitis based on ncRNAs in the future.

Expression profile of long non-coding RNAs in the intestine of black rockfish Sebastes schlegelii in response to Edwardsiella tarda infection

Long non-coding RNAs(lncRNAs)are a class of transcripts longer than 200 bp,which have been emerged as essential regulators in numerous biological processes.Black rockfish(Sebastes schlegelii)is an economic fish that widely cultured in the coastal areas of China,Japan,and South Korea.With the expansion of aquacultural scale,various pathogens have threatened its industry and reduced its economic values.It has been reported that lncRNA were involved in the immune response and metabolic pathway in teleost,while no study is available on identification and functional analysis of lncRNAs in black rockfish so far.Herein,this study was performed to identify lncRNAs in the intestine of black rockfish after Edwardsiella tarda infection.In our results,a total of 9311 lncRNAs were identified through highthroughput sequencing,and 102 lncRNAs were significantly regulated following challenge,which were predicted to target 3348 mRNAs.Results of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the se target genes showed they were function in catalytic activity,hydrolase activity,defense response and peptidase activity,which involved in metabolic pathways and immune related pathways.In addition,47 lncRNAs and 8 differentially expressed mRNAs(DEmRNAs)showed co-expression at two or more infection time points with metabolism and immunity functions.Moreover,real-time quantitative PCR(qRT-PCR)was performed to verify the reliability of sequencing gene expression analysis results.This research laid the foundation for further investigation of the regulatory roles of lncRNAs in the intestinal immune response of black rockfish.

A double-edged sword:The HBV-induced non-coding RNAs alterations in hepatocellular carcinoma

Non-coding RNAs are speculated to exert important regulatory functions at the level of gene expression,oncogenesis,and many other pathologies.Hepatitis B virus(HBV)infection is a leading cause of hepatocellular carcinoma(HCC),and some studies have shown that the expression of non-coding RNAs has an assignable effect on the development of HBV-induced HCC.In this context,the functions and molecular mechanisms of the HBVinduced non-coding RNA expression in the development of hepatoma have attracted increasing attention.This review covers the progress in the exploration of the relationship between HBV-induced hepatoma and non-coding RNA expression,cataloging the recent reports about the roles of non-coding RNAs in HBV-induced hepatoma into five classes,including(1)modulation of metabolism in hepatic cancer,(2)aggravation of inflammation and hepatic fibrosis,(3)alteration of the tumor immune microenvironment,(4)non-coding RNA N6-methyladenosine modification,and a seemingly opposite process,(5)the suppression of the progression of HBV-related HCC.All evidence supports non-coding RNAs as promising novel targets for the early diagnosis and treatments for HCC.

Bioinformatics Analysis and Experimental Verification of Prognostic and Biological Significance of Autophagy-Related Long Non-Coding RNAs in Gastric Carcinoma

Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic analysis of GC patients’gene expression profiling data from the Cancer Genome Atlas database was performed to identify autophagy-related lncRNAs that are associated with predictive risk.Through Cox regression and Lasso regression analyses,the autophagy-related lncRNAs that are associated with prognosis were identified,and a novel prognostic model for GC was established.The model was then used to evaluate the clinical features and predictive risk of individuals with GC.By using two datasets,GSE 62254(n=300)and GSE 15459(n=192),from Gene Expression Omnibus,its effectiveness was verified.Gene set enrichment analysis according to hallmark and Kyoto Encyclopedia of Genes and Genomes were used to determine the possible biological roles of these lncRNAs.Furthermore,the HOXD antisense growth-associated long non-coding RNA(HAGLR)mechanism in GC was discovered through in vitro and in vivo experiments.Results:Six lncRNAs associated with autophagy in GC were identified,and a new prognostic risk model based on these lncRNAs was established.The six-lncRNA signature was significantly associated with adverse clinicopathological features and found to be an independent GC prognostic factor.The model was proven to be effective and robust by GSE62254 and GSE15459.According to gene set enrichment analysis,the six lncRNAs appeared to be tightly linked to autophagy-related and cancer-related mechanisms.HAGLR was also found to promote tumor growth by enhancing autophagy signaling in GC.Conclusion:A novel prognostic model integrating HAGLR that can effectively evaluate and predict the prognostic risk of GC patients was established.The results indicated that HAGLR promotes gastric cancer progression by enhancing autophagy and is anticipated to be a potential new target for the treatment of gastric cancer.

The role of small non-coding RNAs(sncRNAs)in male infertility:A scoping review

Objective:To give a brief overview of the field of epigenetics and the potential predictive power that small non-coding RNA(sncRNA)may hold in relation to improving the treatment and diagnosis of male infertility.Methods:PRISMA-ScR was used as the scoping review guideline for this investigation.All article data here have been accessed from MEDLINE–PubMed,Science Direct,EBSCO,Scopus,Sage Journals,and Google Scholar.The terms"small non coding RNA,male,infertility,miRNA,sperm"were used in the search between 2015 and 2023.Results:The study comprised 35 publications in total.Several sncRNAs,miR-155,miR-16,miR-196,miR-525-3p,miR-891 were found to be effective in regulating the mechanism of spermatozoa processing in the infertility of men.sncRNA can be used as a biomarker of male infertility.Conclusions:sncRNAs can act as biomarkers for the diagnosis of reproductive diseases.Actually,by recognizing sncRNAs and their mechanisms,a new way to treat infertile men would be paved.The functional annotation of sncRNAs in spermatogenesis is still in its infancy but has enormous potential.This is despite the fact that many potential sncRNAs have been found to date with the use of cutting-edge technology and publicly accessible sncRNA annotation tools.

Non-coding RNAs and other determinants of neuroinflammation and endothelial dysfunction:regulation of gene expression in the acute phase of ischemic stroke and possible therapeutic applications

Ischemic stroke occurs under a variety of clinical conditions and has different pathogeneses,resulting in necrosis of brain parenchyma.Stroke pathogenesis is characterized by neuroinflammation and endothelial dysfunction.Some of the main processes triggered in the early stages of ischemic damage are the rapid activation of resident inflammatory cells(microglia,astrocytes and endothelial cells),inflammatory cytokines,and translocation of intercellular nuclear factors.Inflammation in stroke includes all the processes mentioned above,and it consists of either protective or detrimental effects concerning the“polarization”of these processes.This polarization comes out from the interaction of all the molecular pathways that regulate genome expression:the epigenetic factors.In recent years,new regulation mechanisms have been cleared,and these include non-coding RNAs,adenosine receptors,and the activity of mesenchymal stem/stromal cells and microglia.We reviewed how long non-coding RNA and microRNA have emerged as an essential mediator of some neurological diseases.We also clarified that their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic stroke.To date,we do not have adequate tools to control pathophysiological processes associated with stroke.Our goal is to review the role of non-coding RNAs and innate immune cells(such as microglia and mesenchymal stem/stromal cells)and the possible therapeutic effects of their modulation in patients with acute ischemic stroke.A better understanding of the mechanisms that influence the“polarization”of the inflammatory response after the acute event seems to be the way to change the natural history of the disease.