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Objective: Diabetic foot ulcers (DFU) are one of the most destructive complications of diabetes mellitus. The aim of this study was to link miR‐155 and SOX2 with DFU to explore the regulation of wound healing by DFU and its potential mechanism. Methods: Human keratinocytes (HaCaT) were induced with advanced glycation end products (AGEs) to construct DFU models in vitro. AGE‐induced HaCaT cells were subjected to CCK‐8 assays, flow cytometry, and wound healing assays to evaluate cell proliferation, apoptosis, and migration capacity, respectively. RT–qPCR and Western blotting were used to determine gene and protein expression levels, respectively. N6‐methyladenosine (M6A) levels in total RNA were assessed using an M6A methylation quantification kit. Results: Our results suggested that the inhibition of miR‐155 promoted wound healing in an in vitro DFU model, while the knockdown of HIF‐1α reversed this process, and that HIF‐1α was a target protein of miR‐155. In addition, knockdown of HIF‐1α promoted the m6A level of SOX2 mRNA, inhibited the expression of SOX2, and inhibited the activation of the EGFR/MEK/ERK signaling pathway, thus inhibiting the proliferation and migration of HaCaT cells and promoting the apoptosis of HaCaT cells, while overexpression of SOX2 reversed this effect. We also found that METTL3 knockdown had the opposite effect of HIF‐1α knockdown. Conclusions: Inhibition of miR‐155 promoted the expression of HIF‐1α and attenuated the m6A modification of SOX2 mRNA, thereby promoting the expression of SOX2 and activating the downstream EGFR/MEK/ERK signaling pathway to promote wound healing in an in vitro DFU model. [ABSTRACT FROM AUTHOR]

We explored key microRNAs (miRNAs) related to tumorigenesis and immune modulation in glioblastoma (GBM), employing in silico, in vitro, and ex vivo analysis along with an assessment of the cellular impacts resulting from miRNA inhibition. GBM and T cells miRNA expression profiles from public datasets were used to evaluate differentially expressed miRNAs (DEmiRNAs). Some DEmiRNAs were chosen for validation in GBM cell lines, primary cell cultures, and brain tumor patient samples, using RT‐qPCR. Target genes and pathways were identified with bioinformatic analyses. In silico functional enrichment analysis revealed that miR‐27a‐3p and miR‐155‐5p modulate immune, metabolic, and GBM‐related pathways. A172 cells were transfected with miRNA inhibitors and the effects on cellular processes and immunomodulation were analyzed by co‐culture assays and flow cytometry. Upon validation, miR‐27a‐3p and miR‐155‐5p miRNAs expressions were consistently increased. Inhibiting these two miRNAs reduced cell viability, but only the inhibition of miR‐27a‐3p led to apoptosis. Co‐culture assays showed an increase in Th1 cells along with elevated Th1/Treg and Th17/Treg ratios, and an increase in Th17 cells exclusively with miR‐155‐5p inhibition. Immune cells' gene expression modulation induced an antitumor profile, concomitant with an increase in the expression of apoptotic genes in cancer cells after co‐culture. This study unveils potential targets for immune and tumor regulation, highlighting overexpressed miRNAs modulation as a novel therapeutic approach for GBM. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is a serious problem that results from systemic lupus erythematosus (SLE) complications. Recent studies have highlighted that non-coding RNA (ncRNA) dysregulation is a notable feature in patients with SLE. As a result, this research was designed to investigate lncRNA CASC2 and miR-155 levels as non-invasive diagnostic biomarkers in SLE patients, including those with and without nephritis, and to investigate their effectiveness in assessing disease severity and predicting LN. Our study included 60 patients with SLE who were subclassified into (30 non-LN and 30 LN groups), along with 30 control subjects. Quantification of lncRNA CASC2 and miR-155 in serum samples from the Egyptian population was carried out with real-time polymerase chain reaction (RT-PCR). The disease activity index (SLEDAI) for SLE was evaluated, and the analysis of the receiver operating characteristic (ROC) curve was implemented. Increased levels of lncRNA CASC2 were observed in SLE patients compared to healthy controls, with even higher levels observed in the LN group versus the non-LN patients' group. Conversely, miR-155 was noted to be down-regulated in SLE patients relative to controls, and its levels were lower in the LN group relative to the non-LN patients' group. The elevated expression of lncRNA CASC2 and reduced expression of miR-155 were both correlated to the severity of the disease. The current study illustrated that both lncRNA CASC2 and miR-155 could act as valuable non-invasive diagnostic biomarkers for SLE and predicting LN among SLE patients, as well as their abilities to detect the disease severity and progression. [ABSTRACT FROM AUTHOR]

Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL). Despite the use of newer agents, such as polatuzumab vedotin, more than one-third of patients have ultimately relapsed or experienced refractory disease. MiRNAs are single-stranded, ~22-nucleotide-long RNAs that interact with their target RNA. They are significant regulators of post-transcriptional gene expression. One significant miRNA, miR-155, is involved in the pathophysiology of DLBCL and it is a critical modulator of hematopoiesis, inflammation, and immune responses. Targets of miR-155, such as histone deacetylase 4 (HDAC4), suppressor of cytokine signaling-1 (SOCS1) and immune cells, play a crucial role in DLBCL pathogenesis, since miR-155 regulates key pathways, transcription factors and cytokine expression and shapes the tumor microenvironment in DLBCL. In this review, we examine the role of miR-155 in DLBCL and its potential as a future diagnostic, prognostic, or predictive biomarker. [ABSTRACT FROM AUTHOR]

BackgroundObjectiveMethodsResultsMicroRNAs have gained attention as key immunomodulators, with miR-155 specifically shown in various studies to drive macrophage polarization toward the classical phenotype. This polarization is crucial, as classical macrophages play a well-recognized role in differentiating type-1 immune responses and resisting Leishmania infection.The present study aims to evaluate the anti-leishmanial immunoadjuvant effects of the miR-155 chitosan polyplex (miR-155 CP).The anti-leishmanial immunoadjuvant activity of miR-155 CP synthesized by the coacervation method was assessed against L. major (MRHO/IR/75/ER) by analyzing the infectivity rate on RAW 264.7 cells in vitro.MiR-155 CP as an adjuvant co-administrated with soluble Leishmania antigen (SLA) for immunization of BALB/c mice, then the challenge was performed by subcutaneous injection of 1 × 106 L. major promastigotes. Eight weeks following the challenge, lesion size, parasite load, cytokine assay, and nitric oxide production were evaluated.The nanoparticles were produced with a size of 233.87 ± 8 nm and a zeta potential of + 22.6 ± 2 mV with good transfection efficiency. The mean infection index among pretreated cells with miR-155 CP (72±1.1) decreased significantly compared to the control group (420 ± 2.8). The parasite burden and the size of the lesions were significantly reduced in the immunized infected mice. Vaccination by miR-155 CP/SLA triggered the production of IFN-γ and NO and changed the cytokine profile of antigen-specific cells.Conclusion:The effectiveness of the SLA vaccine can be enhanced by including miR-155 CP as an adjuvant. SLA and miR-155 CP co-administration improve the type-1 immune response. This enhanced immune response helps prevent severe leishmaniasis. [ABSTRACT FROM AUTHOR]

CD4+ T cells are considered the main orchestrators of autoimmune diseases. Their disruptive effect on CD4+ T cell differentiation and the imbalance between T helper cell populations can be most accurately determined using experimental autoimmune encephalomyelitis (EAE) as an animal model of multiple sclerosis (MS). One epigenetic factor known to promote autoimmune inflammation is miRNA-155 (miR-155), which is significantly upregulated in inflammatory T cells. The aim of the present study was to profile the transcriptome of immunized mice and determine their gene expression levels based on mRNA and miRNA sequencing. No statistically significant differences in miRNA profile were observed; however, substantial changes in gene expression between miRNA-155 knockout (KO) mice and WT were noted. In miR-155 KO mice, mRNA expression in CD4+ T cells changed in response to immunization with the myeloid antigen MOG35-55. After restimulation with MOG35-55, increased Ffar1 (free fatty acid receptor 1) and Scg2 (secretogranin-2) expression were noted in the CD4+ T cells of miR-155-deficient mice; this is an example of an alternative response to antigen stimulation. [ABSTRACT FROM AUTHOR]

Objective: Variants within genes encoding microRNAs (miRNAs) may alter the expression of both miRNAs and their target genes, thus contributing to the etiology of psychiatric disorders. The involvement of miRNAs in neuronal differentiation and synaptic plasticity supported this hypothesis. We aimed to investigate the links between miR-155 rs767649/miR-22 rs8076112 and the risk of panic disorder (PD) in a sample of Turkish population. Methods: In this experimental study, 134 PD patients and 140 healthy controls were recruited. Genotyping was carried out using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. To evaluate PD phenotypes, Panic Disorder Severity Scale (PDSS) was also administered to patients to clarify possible associations between the scale and risk variants analyzed. Results: The genotype analysis of miR-155 rs767649 did not show an association with PD risk and it was not related to the disease severity. For miR-22 rs8076112 variant, a statistically significant association was determined; CC genotypes were lower in patients compared to controls. Logistic regression analysis proved the highly protective effect (80.4%) of CC genotype against PD ( p = 0.041; OR = 0.196, 95% CI = 0.041-0.934). Though its significance in disease liability, miR-22 rs8076112 was not associated with the disease severity. Conclusion: Our findings firstly report the combined analysis of miR-155 rs767649 and miR-22 rs8076112 in PD in terms of both disease susceptibility and severity. These findings await replication in independent cohorts with enrichment of other miRNA gene variants. Thus, certain miRNAs and their target genes involved in the etiology and phenotypes of PD could be enlightened. [ABSTRACT FROM AUTHOR]

Kai Wang, Jihong Zhu, Weibo Gao, Wei Guo, Yang Guo Department of Emergency, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaCorrespondence: Yang Guo; Wei Guo, Email edguoyang@163.com; woaiguowei111@sina.comBackground: Severe sepsis is a systemic inflammatory response syndrome caused by infection, and the Acute Physiological Assessment and Chronic Health Evaluation II (APACHE II) scoring system is widely used to assess the severity of severe patients. Hybrid blood purification treatment (HBPT) and ulinastatin (UTI) have shown good efficacy in a variety of inflammatory diseases, and miR-146a and miR-155 were found to be closely related to inflammatory reaction. The purpose of this study was to investigate the effect of HBPT combined with UTI in the treatment of patients with severe sepsis, especially the effects on APACHE II score and miR-146a and miR-155 levels.Methods: We carried out a retrospective analysis of clinical data with severe sepsis admitted to our hospital from January 2020 to June 2022. The patients were divided into an HBPT or HBPT+UTI group according to the treatment records. The APACHE II score, miR-146a level, miR-155 level, inflammatory factors, and rehabilitation status of both groups were analyzed and compared before and after treatment.Results: A total of 150 were included in the analysis, there were 77 participants in HBPT+UTI and 73 in HBPT group. After treatment, the APACHE II score and levels of miR-146a, miR-155, and inflammatory factors were significantly lower than that before treatment. Furthermore, the HBPT+UTI group showed significantly lower values than the HBPT group (all P < 0.05). The recovery time of serum amylase, the disappearance time of abdominal pain, and the length of hospitalization in the HBPT+UTI group were significantly shorter than those in the HBPT group (all P < 0.05).Conclusion: UTI treatment combined with the administration of HBPT could improve the APACHE II score, alleviate the inflammatory reaction, and significantly improve the short-term prognosis of the patients with severe sepsis.Keywords: hybrid blood purification treatment, ulinastatin, APACHE II score, miR-146a, miR-155, severe sepsis

Abstract Objectives Metabolic syndrome is a cluster of conditions that increases the risk of atherosclerotic cardiovascular diseases. The current study was a randomized, double blind, placebo-controlled study that aimed to determine the impact of green coffee (GC) in obese patients with metabolic syndrome through analysis of miRNA-155, miRNA-133a and the inflammatory biomarkers such as resistin, TNF-α, total sialic acid, homocysteine, high sensitivity C-reactive protein (hs-CRP), and the anti-inflammatory cytokine, adiponectin. Methods One hundred-sixty obese patients were randomly supplemented either with GC capsules (800 mg) or placebo daily for six months. Both groups were advised to take a balanced diet. Blood samples were collected at baseline and after six months of supplementation. Results GC supplementation for 6 months reduced BMI (p = 0.002), waist circumference (p = 0.038), blood glucose (p = 0.002), HbA1c% (p = 0.000), Insulin (p = 0.000), systolic blood pressure (p = 0.005), diastolic BP (p = 0.001) compared with placebo. GC significantly decreased total cholesterol (TC, p = 0.000), LDL-C (p = 0.001), triglycerides (TG, p = 0.002) and increased HDL-C (p = 0.008) compared with placebo group. In addition, GC significantly (p ≤ 0.005) reduced total sialic acid, homocysteine, resistin, TNF-α, hs-CRP and the oxidative stress marker malondialdehyde (MDA), but increased serum adiponectin (p = 0.000) compared to placebo group. There was a significant reduction in the gene expression of miR-133a (p = 0.000) in GC group as compared with baseline levels and with the control placebo group (p = 0.001) after 6 months. Conclusion GC administration modulated metabolic syndrome by decreasing BMI, high BP, blood glucose, dyslipidemia, miRNA-133a and inflammatory biomarkers that constitute risk factors for cardiovascular diseases. ClinicalTrials.gov registration No. is NCT05688917. Graphical Abstract

Sepsis is a life-threatening state of organ dysfunction caused by systemic inflammation and a dysfunctional response to host infections that can induce severe intestinal mucosal damage. Pyroptosis is mediated by the activated NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome after stimulation by various inflammatory factors during sepsis. The inflammatory response is a major driver of intestinal damage during sepsis. Intestinal mucosal barrier dysfunction in sepsis is associated with pyroptosis, a type of programmed inflammatory cell death. Several studies have confirmed the role of miR-155 in sepsis and other diseases. However, the effect of miR-155 on intestinal pyroptosis in the context of intestinal mucosal barrier dysfunction during sepsis remains unclear. Thus, a model of sepsis in Sprague-Dawley rats is established using cecal ligation and puncture (CLP), and a series of molecular biological methods are used in this study. The results show that the expression of miR-155 is increased and that of sirtuin 1 (SIRT1) is decreased in the intestinal tissues of patients with sepsis. miR-155 expression is negatively correlated with SIRT1 expression. Increased miR-155 expression significantly inhibits SIRT1 activity and upregulates the expressions of NOD-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), interleukin-1β (IL-1β) and interleukin-18 (IL-18) to promote pyroptosis. The inhibition of miR-155 expression is associated with increased SIRT1 expression, promotes the deacetylation of p65, and significantly downregulates p65 acetylation. Herein, we propose that miR-155 induces pyroptosis in the intestine partly by regulating SIRT1, thereby reducing the deacetylation of the nuclear factor (NF)-κB subunit p65 and increasing NF-κB signaling activity in sepsis, leading to intestinal barrier damage.

Abstract DHAV-1 is a highly infectious pathogen that can cause acute hepatitis in ducklings. MicroRNA (miRNA) plays an essential regulatory role in virus response. We characterized and compared miRNA and mRNA expression profiles in duck embryonic fibroblasts (DEF) and the liver of ducklings infected with DHAV-1. DHAV-1 infected DEF was divided into infection group (D group) and blank group (M group), and DHAV-1 infected duckling group was divided into infection group (H group) and blank group (N group). D vs. M have 130 differentially expressed (DE) miRNA (DEM) and 2204 differentially expressed (DE) mRNA (DEG), H vs. N have 72 DEM and 1976 DEG. By the intersection of D vs. M and H vs. N comparisons, 15 upregulated DEM, 5 downregulated DEM, 340 upregulated DEG and 50 downregulated DEG were found with both in vivo and in vitro DHAV-1 infection. In particular, we identified the same DE miRNA target genes and functional annotations of DE mRNA. We enriched with multiple gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may have important roles in viral virulence, host immunity, and metabolism. We selected miR-155, which is co-upregulated, and found that miR-155 targets SOCS1 to inhibit DHVA-1 replication.

Abstract Background miR-155 is involved in the generation and maintenance of inflammation and pain, endothelial function and immune system homeostasis, all functions that are relevant for migraine. The present study aims to assess the levels of miR-155 in migraine subtypes (episodic and chronic) in comparison to age- and sex-matched healthy controls. Methods This is a cross-sectional, controlled, study involving three study groups: I) episodic migraine (n = 52, EM), II) chronic migraine with medication overuse (n = 44, CM-MO), and III) healthy controls (n = 32, HCs). We assessed the interictal gene expression levels of miR-155, IL-1β, TNF-α, and IL-10 in peripheral blood monocytes using rtPCR. The monocytic differentiation toward the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes was assessed in circulating monocytes with flow cytometry analysis and cell sorting. Results miR-155 gene expression was higher in CM-MO group (2.68 ± 2.47 Relative Quantification - RQ) when compared to EM group (1.46 ± 0.85 RQ, p = 0.006) and HCs (0.44 ± 0.18 RQ, p = 0.001). In addition, miR-155 gene expression was higher in EM group when compared to HCs (p = 0.001). A multivariate analysis confirmed the difference between EM and CM-MO groups after correction for age, sex, smoking habit, preventive treatment, aura, presence of psychiatric or other pain conditions. We found higher gene expression of IL-1β, TNF-α, and lower gene expression of IL-10 in migraine participants when compared to HCs (p = 0.001 for all comparisons). TNF-α and IL-10 genes alterations were more prominent in CM-MO when compared to EM participants (p = 0.001). miR-155 positively correlated with IL-1β (p = 0.001) and TNF-α (p = 0.001) expression levels. Finally, in people with CM-MO, we described an up-regulated percentage of events in both M1 and M2 monocytic profiles. Conclusions Our study shows for the first time a specific profile of activation of miR-155 gene expression levels in monocytes of selected migraine subpopulations, more pronounced in subjects with CM-MO. Interestingly, mir-155 expression correlated with markers of activation of the inflammatory and immune systems. The CM-MO subpopulation showed a peculiar increase of both pro-inflammatory and anti-inflammatory monocytes which worths further investigation. Trial registration www.clinicaltrials.gov . (NCT05891808).

Incident chronic kidney disease (CKD) varies in populations with hypertension of similar severity. Proteinuria promotes CKD progression in part due to activation of plasminogen to plasmin in the podocytes, resulting in oxidative stress‐mediated injury. Additional mechanisms include deficiency of renal alpha‐klotho, that inhibits Wnt/beta‐catenin, an up regulator of intra‐renal renin angiotensin system (RAS) genes. Alpha‐klotho deficiency therefore results in upregulation of the intra‐renal RAS via Wnt/beta‐catenin. In hypertensive, Dahl salt sensitive (DS) and spontaneously hypertensive rats (SHR), we investigated renal and vascular injury, miR‐155, AT1R, alpha‐klotho, and TNF‐α. Hypertensive high salt DS (DS‐HS), but not SHR developed proteinuria, plasminuria, and glomerulosclerosis. Compared to DS low salt (DS‐LS), in hypertensive DS‐HS alpha‐klotho decreased 5‐fold in serum and 2.6‐fold in kidney, whereas serum mir‐155 decreased 3.3‐fold and AT1R increased 52% in kidney and 77% in aorta. AT1R, alpha‐klotho, and miR‐155 remained unchanged in prehypertensive and hypertensive SHR. TNF‐α increased by 3‐fold in serum and urine of DS‐HS rats. These studies unveiled in salt sensitive DS‐HS, but not in SHR, a genetically conditioned dysfunction of the intermolecular network integrated by alpha‐klotho, RAS, miR‐155, and TNF‐α that is at the helm of their end‐organ susceptibility while plasminuria may participate as a second hit. [ABSTRACT FROM AUTHOR]

DHAV-1 is a highly infectious pathogen that can cause acute hepatitis in ducklings. MicroRNA (miRNA) plays an essential regulatory role in virus response. We characterized and compared miRNA and mRNA expression profiles in duck embryonic fibroblasts (DEF) and the liver of ducklings infected with DHAV-1. DHAV-1 infected DEF was divided into infection group (D group) and blank group (M group), and DHAV-1 infected duckling group was divided into infection group (H group) and blank group (N group). D vs. M have 130 differentially expressed (DE) miRNA (DEM) and 2204 differentially expressed (DE) mRNA (DEG), H vs. N have 72 DEM and 1976 DEG. By the intersection of D vs. M and H vs. N comparisons, 15 upregulated DEM, 5 downregulated DEM, 340 upregulated DEG and 50 downregulated DEG were found with both in vivo and in vitro DHAV-1 infection. In particular, we identified the same DE miRNA target genes and functional annotations of DE mRNA. We enriched with multiple gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may have important roles in viral virulence, host immunity, and metabolism. We selected miR-155, which is co-upregulated, and found that miR-155 targets SOCS1 to inhibit DHVA-1 replication. [ABSTRACT FROM AUTHOR]

Reactive astrocyte activation in the context of cerebral ischemia/reperfusion (I/R) injury gives rise to two distinct subtypes: the neurotoxic A1 type and the neuroprotective A2 type. DJ‐1 (Parkinson disease protein 7, PARK7), originally identified as a Parkinson's disease‐associated protein, is a multifunctional anti‐oxidative stress protein with molecular chaperone and signaling functions. SHP‐1 (Src homology 2 domain‐containing phosphatase‐1) is a protein tyrosine phosphatase closely associated with cellular signal transduction. miR‐155 is a microRNA that participates in cellular functions by regulating gene expression. Recent studies have uncovered the relationship between DJ‐1 and astrocyte‐mediated neuroprotection, which may be related to its antioxidant properties and regulation of signaling molecules such as SHP‐1. Furthermore, miR‐155 may exert its effects by influencing SHP‐1, providing a potential perspective for understanding the molecular mechanisms of stroke. A middle cerebral artery occlusion/reperfusion (MCAO/R) model and an oxygen–glucose deprivation/reperfusion (OGD/R) model were established to simulate focal cerebral I/R injury in vivo and in vitro, respectively. The in vivo interaction between DJ‐1 and SHP‐1 has been experimentally validated through immunoprecipitation. Overexpression of DJ‐1 attenuates I/R injury and suppresses miR‐155 expression. In addition, inhibition of miR‐155 upregulates SHP‐1 expression and modulates astrocyte activation phenotype. These findings suggest that DJ‐1 mediates astrocyte activation via the miR‐155/SHP‐1 pathway, playing a pivotal role in the pathogenesis of cerebral ischemia–reperfusion injury. Our results provide a potential way for exploring the pathogenesis of ischemic stroke and present promising targets for pharmacological intervention. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is the leading cause of traumatic death worldwide and is a public health problem associated with high mortality and morbidity rates, with a significant socioeconomic burden. The diagnosis of brain injury may be difficult in some cases or may leave diagnostic doubts, especially in mild trauma with insignificant pathological brain changes or in cases where instrumental tests are negative. Therefore, in recent years, an important area of research has been directed towards the study of new biomarkers, such as micro-RNAs (miRNAs), which can assist clinicians in the diagnosis, staging, and prognostic evaluation of TBI, as well as forensic pathologists in the assessment of TBI and in the estimation of additional relevant data, such as survival time. The aim of this study is to investigate the expression profiles (down- and upregulation) of a panel of miRNAs in subjects deceased with TBI in order to assess, verify, and define the role played by non-coding RNA molecules in the different pathophysiological mechanisms of brain damage. This study also aims to correlate the detected expression profiles with survival time, defined as the time elapsed between the traumatic event and death, and with the severity of the trauma. This study was conducted on 40 cases of subjects deceased with TBI (study group) and 10 cases of subjects deceased suddenly from non-traumatic causes (control group). The study group was stratified according to the survival time and the severity of the trauma. The selection of miRNAs to be examined was based on a thorough literature review. Analyses were performed on formalin-fixed, paraffin-embedded (FFPE) brain tissue samples, with a first step of total RNA extraction and a second step of quantification of the selected miRNAs of interest. This study showed higher expression levels in cases compared to controls for miR-16, miR-21, miR-130a, and miR-155. In contrast, lower expression levels were found in cases compared to controls for miR-23a-3p. There were no statistically significant differences in the expression levels between cases and controls for miR-19a. In cases with short survival, the expression levels of miR-16-5p and miR-21-5p were significantly higher. In cases with long survival, miR-21-5p was significantly lower. The expression levels of miR-130a were significantly higher in TBI cases with short and middle survival. In relation to TBI severity, miR-16-5p and miR-21-5p expression levels were significantly higher in the critical–fatal TBI subgroup. Conclusions: This study provides evidence for the potential of the investigated miRNAs as predictive biomarkers to discriminate between TBI cases and controls. These miRNAs could improve the postmortem diagnosis of TBI and also offer the possibility to define the survival time and the severity of the trauma. The analysis of miRNAs could become a key tool in forensic investigations, providing more precise and detailed information on the nature and extent of TBI and helping to define the circumstances of death. [ABSTRACT FROM AUTHOR]

MiR-155 is a multifunctional microRNA involved in many biological processes. Since miR-155 is overexpressed in several pathologies, its detection deserves high interest in clinical diagnostics. Biosensing approaches often exploit the hybridization of miR-155 with its complementary strand. Molecular Dynamics (MD) simulations were applied to investigate the complex formed by miR-155 and its complementary strand in aqueous solution with Na+ and Cl− ions at ionic strengths in the 100–400 mM range, conditions commonly used in biosensing experiments. We found that the main structural properties of the duplex are preserved at all the investigated ionic strengths. The radial distribution functions of both Na+ and Cl− ions around the duplex show deviation from those of bulk with peaks whose relative intensity depends on the ionic strength. The number of ions monitored as a function of the distance from the duplex reveals a behavior reminiscent of the counterion condensation near the duplex surface. The occurrence of such a phenomenon could affect the Debye length with possible effects on the sensitivity in biosensing experiments. [ABSTRACT FROM AUTHOR]

Objective To investigate changes and clinical significance of serum microRNA-155 (miR-155) and microRNA-205-5p (miR-205-5p) levels in patients with hepatitis C virus (HCV) infection. Methods A total of 141 patients with HCV infection were collected and divided into the HCV-1b group (92 cases) and the non HCV-1b group (49 cases) according to their genotype, and another 141 healthy volunteers who underwent physical examinations in our hospital during the same period were collected as the control group. The general information, biochemical indicators and serum levels of miR-155 and miR-205-5p were compared between the three groups. According to the grading of hepatitis activity, HCV infected patients were classified into the G0, G1, G2, G3 and G4 groups, and serum levels of miR-155 and miR-205-5p were compared between the five groups. Receiver operating characteristics (ROC) curve was used to analyze clinical values of serum miR-155 and miR-205-5p in diagnosing hepatitis activity of G1-G4 in patients with HCV infection. Results The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were obviously higher in the HCV-1b group and the non HCV-1b group than those in the control group, while the level of ALB was obviously lower than that in the control group (P＜0.05). The serum level of miR-155 was increased in turn in the control group, the nonHCV-1b group and the HCV-1b group, and the serum level of miR-205-5p was decreased in turn (P＜0.05). The serum level of miR-155 increased in turn with the increased grading of hepatitis activity, while the serum miR-205-5p level decreased in turn (P＜0.05). The area under curve (AUC) values of serum miR-155, miR-205-5p and their combination in diagnosing hepatitis activity of G1-G4 in HCV infected patients were 0.855, 0.793 and 0.913, respectively, and the combination of the two is superior to each individual diagnosis (P＜0.05). Conclusion The serum miR-155 level increases and miR-205-5p level decreases in HCV infected patients. The combination of the two has high efficacy in diagnosing hepatitis activity of G1-G4 in HCV infected patients. [ABSTRACT FROM AUTHOR]

Background: Ineffective erythropoiesis (IE) is the primary cause of anemia and associated pathologies in β-thalassemia. The characterization of IE is imbalance of erythroid proliferation and differentiation, resulting in increased erythroblast proliferation that fails to differentiate and gives rise to enucleate RBCs. MicroRNAs (miRs) are known to play important roles in hematopoiesis. miR-155 is a multifunctional molecule involved in both normal and pathological hematopoiesis, and its upregulation is observed in patients with β-thalassemia/HbE. However, the expression and function of miR-155, especially in β-thalassemia, have not yet been explored. Methods: To study miR-155 expression in thalassemia, erythroblast subpopulations, CD45-CD71+Ter-119+ and CD45-CD71−Ter-119+ were collected from βIVSII-654 thalassemic bone marrow. Additionally, a two-phase culture of mouse bone marrow erythroid progenitor cells was performed. Expression of miR-155 and predicted mRNA target genes, c-myc, bach-1 and pu-1, were determined by quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and normalized to small nucleolar RNA (snoRNA) 202 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively. To investigate the effect of miR-155 expression, erythroblasts were transfected with miR-inhibitor and -mimic in order to elevate and eliminate miR-155 expression, respectively. Erythroid cell differentiation was evaluated by Wright–Giemsa staining and flow cytometry. Results: miR-155 was upregulated, both in vivo and in vitro, during erythropoiesis in β-thalassemic mice. Our study revealed that gain- and loss of function of miR-155 were involved in erythroid proliferation and differentiation, and augmented proliferation and differentiation of thalassemic mouse erythroblasts may be associated with miR-155 upregulation. miR-155 upregulation in β-thalassemic mice significantly increased the percentage of basophilic and polychromatic erythroblasts. Conversely, a significant decrease in percentage of basophilic and polychromatic erythroblasts was observed in β-thalassemic mice transfected with anti-miR-155 inhibitor. We also examined the mRNA targets (c-myc, bach-1 and pu-1) of miR-155, which indicated that c-myc is a valid target gene of miR-155 that regulates erythroid differentiation. Conclusion: miR-155 regulates IE in β-thalassemia via c-myc expression controlling erythroblast proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Background: miR-155 is involved in the generation and maintenance of inflammation and pain, endothelial function and immune system homeostasis, all functions that are relevant for migraine. The present study aims to assess the levels of miR-155 in migraine subtypes (episodic and chronic) in comparison to age- and sex-matched healthy controls. Methods: This is a cross-sectional, controlled, study involving three study groups: I) episodic migraine (n = 52, EM), II) chronic migraine with medication overuse (n = 44, CM-MO), and III) healthy controls (n = 32, HCs). We assessed the interictal gene expression levels of miR-155, IL-1β, TNF-α, and IL-10 in peripheral blood monocytes using rtPCR. The monocytic differentiation toward the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes was assessed in circulating monocytes with flow cytometry analysis and cell sorting. Results: miR-155 gene expression was higher in CM-MO group (2.68 ± 2.47 Relative Quantification - RQ) when compared to EM group (1.46 ± 0.85 RQ, p = 0.006) and HCs (0.44 ± 0.18 RQ, p = 0.001). In addition, miR-155 gene expression was higher in EM group when compared to HCs (p = 0.001). A multivariate analysis confirmed the difference between EM and CM-MO groups after correction for age, sex, smoking habit, preventive treatment, aura, presence of psychiatric or other pain conditions. We found higher gene expression of IL-1β, TNF-α, and lower gene expression of IL-10 in migraine participants when compared to HCs (p = 0.001 for all comparisons). TNF-α and IL-10 genes alterations were more prominent in CM-MO when compared to EM participants (p = 0.001). miR-155 positively correlated with IL-1β (p = 0.001) and TNF-α (p = 0.001) expression levels. Finally, in people with CM-MO, we described an up-regulated percentage of events in both M1 and M2 monocytic profiles. Conclusions: Our study shows for the first time a specific profile of activation of miR-155 gene expression levels in monocytes of selected migraine subpopulations, more pronounced in subjects with CM-MO. Interestingly, mir-155 expression correlated with markers of activation of the inflammatory and immune systems. The CM-MO subpopulation showed a peculiar increase of both pro-inflammatory and anti-inflammatory monocytes which worths further investigation. Trial registration: www.clinicaltrials.gov. (NCT05891808). [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between the expression of microRNA-155 (mi R-155) and microRNA-202 (mi R-202) and the expression of proliferation and invasion genes, clinicopathological parameters and prognosis in endometrial carcinoma (EC) tissue. Methods: 135 EC patients who were underwent surgical treatment in our hospital from October 2015 to October 2018 were selected as observation group, and 135 patients with uterine fibroids who were underwent total hysterectomy during the same period were selected as control group, the expression of mi R-155, mi R-202 and proliferation genes (Cdk4, Cdk6, Efemp2, DJ-1, RRM2) and invasion genes (Dkk1, Ezh2, HMGB1) in two groups were detected and compared by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), the relationship between the expression of mi R-155 and mi R-202 in EC tissues and the clinicopathological parameters of patients were analyzed. The 5 years cumulative survival rate of high expression and low expression of mi R-155 and mi R-202 were analyzed by Kaplan-Meier survival curve. Results: The relative expression levels of mi R-155, Ezh2, HMGB1, Cdk4,Cdk6, DJ-1 and RRM2 in observation group were higher than those in control group, and the relative expression levels of mi R-202, Dkk1and Efemp2 were lower than those in control group (P＜0.05). The relative expression of mi R-155 was positively correlated with Cdk4,Cdk6, DJ-1, RRM2, Ezh2 and HMGB1, and negatively correlated with Efemp2 and Dkk1 (P＜0.05). The relative expression of mi R-202was positively correlated with Efemp2 and Dkk1, and negatively correlated with Cdk4,Cdk6, DJ-1, RRM2, Ezh2 and HMGB1 (P＜0.05). The higher the FIGO stage of EC patients, the lower the degree of differentiation, the deeper the myometrial invasion and the higher the relative expression of mi R-155 in patients with lymph node metastasis, the lower the relative expression of mi R-202 (P＜0.05). The 5years overall survival rate in high mi R-155 group was 68.66%, which was lower than that 87.50% in low mi R-155 group (P＜0.05). The 5years survival rate in high mi R-202 group was 91.80%, which was higher than that 65.71% in low mi R-202 group (P＜0.05). Conclusion: The expression of mi R-155 increase and the expression of mi R-202 decrease in EC tissues, which are significantly correlate with the expression of proliferation and invasion genes, FIGO stage, differentiation degree, depth of myometrial invasion and lymph node metastasis, the higher the expression of mi R-155, the lower the expression of mi R-202, and the worse the prognosis of patients. [ABSTRACT FROM AUTHOR]

Background: Inguinal hernia is a relatively common condition. Most patients with inguinal hernia require surgery. At present, mesh repair is one of the most effective methods to treat inguinal hernia, but insertion of the mesh can cause inflammation. Dexamethasone (DEX) can treat inflammation, but the mechanism by which DEX alleviates inflammation caused by inguinal hernia mesh placement remains unclear. Method: We randomly divided rats into groups: negative control (NC), inguinal hernia (IH), polypropylene mesh (PM), DEX treatment, and miR-155 treatment groups. RT-qPCR was performed to determine the expression of miR-155. ELISA was implemented to determine the secretion of IL-1β, IL-6, and IL-18. Western blotting was used to detect caspase-1, JAK1, p-JAK1, STAT3, and p-STAT3 expression. A dual-luciferase reporter gene array identified a connection between miR-155 and JAK1. Results: The results revealed that the expression of miR-155, IL-1β, IL-6, and IL-18 was upregulated in the PM group. After DEX treatment, the secretion of miR-155, caspase-1, IL-1β, IL-6, and IL-18 decreased. Dual luciferase results confirmed that miR-155 induced the targeted downregulation of JAK1, while a miR-155 mimic reversed the therapeutic effect of DEX, and the expression levels of p-JAK1 and p-STAT3 increased. Conclusion: DEX regulates the JAK1/STAT3 signaling pathway through miR-155 to relieve inflammation caused by inguinal hernia meshes. [ABSTRACT FROM AUTHOR]

5-aminosalicylic acid (5-ASA) is a first-line treatment for maintaining colitis remission. It is a highly effective, safe, and well-tolerated drug with anti-inflammatory and chemo-preventive properties. While patients with primary sclerosing cholangitis (PSC) with concomitant ulcerative colitis are treated with 5-ASA, the molecular mechanisms underlying the drug's chemo-preventive effects are not entirely understood. We previously reported that bile acids and lipopolysaccharide-induced miR-155 expression was associated with downregulating mismatch repair (MMR) proteins in CACO-2 cell lines. Therefore, in this investigation, a set of in vitro functional studies was performed to show the possible mechanisms behind the epigenetic relationship between miR-155 and 5-ASA's prevention of high microsatellite instability (MSI-H). In transient transfection with miR-155Mimic, which behaves like endogenous miRNA, we confirmed the relationships between miR-155 and its target MMR in three human intestinal epithelial cell lines: CACO-2, NCM460D and HT-29. We have shown, for the first time, that 5-ASA modulates MLH1, MSH2, MSH6 in miR-155 transfected cells. These findings underline that chemoprotective 5-ASA therapy can effectively attenuate the expression of miR-155 and potentially prevent a development of MSI-H in a subset of colorectal cancers associated with PSC. Key Points: miR-155 may be a key regulator of tumorigenesis in the ascending colon of patients with PSC. 5-ASA therapy can effectively attenuate the expression of miR-155 involved in the pathogenesis of high microsatellite instability. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluated the expression levels of two hepato-specific microRNAs, miR-122 and miR-155, in hepatocytes exposed to valproic acid (VPA). Topics discussed include therapeutic use of VPA, effect of the VPA on the viability of HepG2 cells, and findings on the role of miR-122 and miR-155 in VPA detoxification.

Hua Ji,1,&ast; YaTing Lu,1,&ast; Gui Liu,2 Xiaotong Zhao,1 Murong Xu,1 Mingwei Chen1 1Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, People’s Republic of China; 2Department of Endocrinology, The Second People’s Hospital of Lu’an City, Lu’an City, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingwei Chen, Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei City, Anhui Province, People’s Republic of China, Email chmw1@163.comObjective: To Study the Correlations of microRNA-155 (miR-155) and microRNA-146a (miR-146a) Expression in Peripheral Blood of Type 2 Diabetes Mellitus (T2DM) Patients with Diabetic Peripheral Neuropathy (DPN), and Explore the Clinical Value of miR-155 and miR-146a in the Diagnosis and Treatment Outcomes of DPN.Methods: The study included 51 T2DM patients without DPN (T2DM group), 49 T2DM patients with DPN (DPN group), and 50 normal controls (NC group). Quantitative real-time PCR was utilized to determine the expression levels of miR-155 and miR-146a. Clinical features and risk factors for DPN were assessed. Multivariate stepwise logistic regression analysis was conducted to confirm whether the expressions of miR-155 and miR-146a could independently predict the risk of DPN. ROC curve analysis evaluated their diagnostic value.Results: The T2DM group exhibited significantly lower expression levels of miR-155 and miR-146a compared to the NC group (P < 0.05). Moreover, the DPN group exhibited a significantly decreased expression level of miR-155 and miR-146a compared to the T2DM group (P < 0.01). Multivariate logistic regression analysis indicated that higher levels of miR-155 and miR-146a might serve as protective factors against DPN development. ROC curve analysis revealed that miR-155 (sensitivity 91.8%, specificity 37.3%, AUC 0.641,) and miR-146a (sensitivity 57.1%, specificity 84.3%, AUC 0.722) possess a strong ability to discriminate between T2DM and DPN. Their combined use further enhanced the diagnostic potential of DPN (sensitivity 83.7%, specificity 60.8%, AUC 0.775). A multi-index combination can improve DPN diagnostic efficiency.Conclusion: The decreased expression of miR-155 and miR-146a in the peripheral blood of T2DM patients is closely related to the occurrence of DPN, highlighting their potential as valuable biomarkers for diagnosing and prognosticating DPN.Keywords: miR-155, miR-146a, diabetic peripheral neuropathy, type 2 diabetes mellitus, biomarkers

Abstract Background M1 macrophages are closely associated with cardiac injury after myocardial infarction (MI). Increasing evidence shows that exosomes play a key role in pathophysiological regulation after MI, but the role of M1 macrophage-derived exosomes (M1-Exos) in myocardial regeneration remains unclear. In this study, we explored the impact of M1 macrophage-derived exosomes on cardiomyocytes regeneration in vitro and in vivo. Methods M0 macrophages were induced to differentiate into M1 macrophages with GM-CSF (50 ng/mL) and IFN-γ (20 ng/mL). Then M1-Exos were isolated and co-incubated with cardiomyocytes. Cardiomyocyte proliferation was detected by pH3 or ki67 staining. Quantitative real-time PCR (qPCR) was used to test the level of miR-155 in macrophages, macrophage-derived exosomes and exosome-treated cardiomyocytes. MI model was constructed and LV-miR-155 was injected around the infarct area, the proliferation of cardiomyocytes was counted by pH3 or ki67 staining. The downstream gene and pathway of miR-155 were predicted and verified by dual-luciferase reporter gene assay, qPCR and immunoblotting analysis. IL-6 (50 ng/mL) was added to cardiomyocytes transfected with miR-155 mimics, and the proliferation of cardiomyocytes was calculated by immunofluorescence. The protein expressions of IL-6R, p-JAK2 and p-STAT3 were detected by Western blot. Results The results showed that M1-Exos suppressed cardiomyocytes proliferation. Meanwhile, miR-155 was highly expressed in M1-Exos and transferred to cardiomyocytes. miR-155 inhibited the proliferation of cardiomyocytes and antagonized the pro-proliferation effect of interleukin 6 (IL-6). Furthermore, miR-155 targeted gene IL-6 receptor (IL-6R) and inhibited the Janus kinase 2(JAK)/Signal transducer and activator of transcription (STAT3) signaling pathway. Conclusion M1-Exos inhibited cardiomyocyte proliferation by delivering miR-155 and inhibiting the IL-6R/JAK/STAT3 signaling pathway. This study provided new insight and potential treatment strategy for the regulation of myocardial regeneration and cardiac repair by macrophages.

Abstract Background Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. Methods Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155−/− mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. Results Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. Conclusions Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.

Background: Micro RNA155 (miR-155) was identified as an essential determinant in immunological responses, and its genetic variants have increasing attention due to their ability to modulate its expression and potentially influence the susceptibility to autoimmune illnesses including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, etc.Objectives: To examine the impact of miR-155 gene polymorphism (rs767649A>T) and miR-155 gene expression and their association with multiple sclerosis (MS) in a sample of Iraqi patients.Materials and Methods: A total of 75 blood specimens were obtained from individuals diagnosed with MS. While an additional 75 blood specimens were collected from evidently healthy participants serving as a control group, with an age ranged 20-71 years. miR-155 gene polymorphism (rs767649 A>T) was determined utilizing Tetra-ARMS Polymerase Chain Reaction (Tetra-ARMS PCR) and miR-155 expression was evaluated using Real-time Polymerase Chain Reaction (RT-PCR).Results: The females experienced MS at a higher rate (69.33%) compared to the males. Furthermore, the age group 30-39 years showed a greater susceptibility to the disease (54.67%). The analysis of miR-155 (rs767649 A>T) SNP in MS patients indicated that 7 (9.34%) had the wild genotype (AA(, 31 (41.33%) had the heterogeneous genotype )AT(, and 37 (49.33%) had the mutant genotype )TT(. These differences were statistically significant (P-value = 0.040). A allele frequency was 45 (0.3) (OR: 0.25; CI: 0.15-0.41) and T allele frequency was 105 (0.7) (OR: 3.91; CI: 2.42-6.33) in MS patients. While analysis of miR-155 gene expression demonstrated a significant increase in the patient group (1.82 ± 0.25 fold) compared to the healthy control group (0.33 ± 0.13 fold). The relationship between miR-155 gene expression and miR-155 genotypes in MS patients, revealed a notable elevation in miR-155 gene expression at the TT genotype (3.15 ± 0.73 fold), followed by TA genotype (1.29 ±0.65fold) and finally AA genotype (0.37 ± 0.19 fold) with highly statistically significant difference (P-value = 0.001). Conclusion: There was a significant positive correlation between miR-155 (rs767649 A>T) genotypes and miR-155 expression and susceptibility to MS in Iraqi patients. These findings suggests that miR-155 may hold potential as a diagnostic and therapeutic marker for the disease.

Background & objectives: The current investigation was carried out to evaluate the expression of MicroRNAs miR-193, miR-122 and miR-155 and lipid profile in antimony-susceptible and resistance patients with cutaneous leishmaniasis. Methods: Lesion and blood samples were collected from 27 antimony-resistance and 27 antimony-susceptible patients. mRNA was extracted and synthase to the cDNA using commercial kits according to the manufacturers’ guideline. The expression of miR-193, miR-122 and miR-155 were evaluated using Real-Time PCR technique. The serum lipid profiles were measured by enzymatic methods. Results: Our results indicated that the expression of miR-193, miR-122 and miR-155 was significantly higher in antimony-susceptible patients. The results of current study indicated that downregulation of miRNAs is coupled with low serum LDL-C and triglyceride. Interpretation & conclusion: The downregulation of miRNAs and decrease in lipid levels may be one of the mechanisms of the parasite to escape from host immune system.

Abstract Objective The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU). Methods The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues. Results Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats. Conclusion Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway.

BACKGROUND: Abnormal activation of osteoclasts plays an important role in the bone destruction due to spinal tuberculosis. During the pathogenesis of osteoporosis, miR-155 knockdown activates adenosine phosphate-dependent protein kinase (AMPK) by increasing the expression of leptin receptors, thereby inhibiting osteoclast differentiation and bone resorption. However, the role of miR-155/leptin receptor(LEPR)/AMPK axis in the bone destruction due to spinal tuberculosis remains unclear. OBJECTIVE: To investigate the role and mechanism of miR-155/LEPR/AMPK axis in tuberculin-induced osteoclast formation. METHODS: RAW264.7 cells were cultured and treated with different concentrations of purified protein derivative (PPD) (1.0, 2.5, 5.0, 10.0 IU/mL) and transfected with negative control (NC) sequence or miR-155 inhibitor, NC siRNA sequence or LEPR siRNA sequence. Tartrate resistant acid phosphatase staining was used to detect the number of osteoclasts. Fluorescence quantitative PCR was used to detect the expression of miR-155. Western blot was used to detect the expression of LEPR and p-AMPK. Double luciferase reporter gene was used to verify miR-155 targeting LEPR. RESULTS AND CONCLUSION: Compared with the control group, the number of osteoclasts and the expression level of miR-155 significantly increased, while the expression level of LEPR and p-AMPK significantly decreased in 2.5, 5.0, and 10.0 IU/mL PPD groups (P < 0.05). Compared with NC+5.0 IU/mL PPD group, the number of osteoclasts and the expression level of miR-155 significantly decreased, while the expression level of LEPR and p-AMPK significantly increased in the miR-155 inhibitor+5.0 IU/mL PPD group (P < 0.05). Compared with the NC group, the fluorescence activity of LEPR wild-type double luciferase reporter gene was increased in the miR-155 inhibitor group, and decreased in the miR-155 mimic group (P < 0.05). Compared with si-NC+miR-155 inhibitor+5.0 IU/ mL PPD group, the expression level of miR-155 had no significant change, the number of osteoclasts significantly increased, and the expression levels of LEPR and p-AMPL significantly decreased in si-LEPR+miR-155 inhibitor+5.0 IU/mL PPD group (P < 0.05). To conclude, tuberculin can induce osteoclast formation by increasing miR-155 expression and inhibiting downstream LEPR expression and AMPK activation. [ABSTRACT FROM AUTHOR]

Background: M1 macrophages are closely associated with cardiac injury after myocardial infarction (MI). Increasing evidence shows that exosomes play a key role in pathophysiological regulation after MI, but the role of M1 macrophage-derived exosomes (M1-Exos) in myocardial regeneration remains unclear. In this study, we explored the impact of M1 macrophage-derived exosomes on cardiomyocytes regeneration in vitro and in vivo. Methods: M0 macrophages were induced to differentiate into M1 macrophages with GM-CSF (50 ng/mL) and IFN-γ (20 ng/mL). Then M1-Exos were isolated and co-incubated with cardiomyocytes. Cardiomyocyte proliferation was detected by pH3 or ki67 staining. Quantitative real-time PCR (qPCR) was used to test the level of miR-155 in macrophages, macrophage-derived exosomes and exosome-treated cardiomyocytes. MI model was constructed and LV-miR-155 was injected around the infarct area, the proliferation of cardiomyocytes was counted by pH3 or ki67 staining. The downstream gene and pathway of miR-155 were predicted and verified by dual-luciferase reporter gene assay, qPCR and immunoblotting analysis. IL-6 (50 ng/mL) was added to cardiomyocytes transfected with miR-155 mimics, and the proliferation of cardiomyocytes was calculated by immunofluorescence. The protein expressions of IL-6R, p-JAK2 and p-STAT3 were detected by Western blot. Results: The results showed that M1-Exos suppressed cardiomyocytes proliferation. Meanwhile, miR-155 was highly expressed in M1-Exos and transferred to cardiomyocytes. miR-155 inhibited the proliferation of cardiomyocytes and antagonized the pro-proliferation effect of interleukin 6 (IL-6). Furthermore, miR-155 targeted gene IL-6 receptor (IL-6R) and inhibited the Janus kinase 2(JAK)/Signal transducer and activator of transcription (STAT3) signaling pathway. Conclusion: M1-Exos inhibited cardiomyocyte proliferation by delivering miR-155 and inhibiting the IL-6R/JAK/STAT3 signaling pathway. This study provided new insight and potential treatment strategy for the regulation of myocardial regeneration and cardiac repair by macrophages. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. Methods: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155−/− mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. Results: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. Conclusions: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury. [ABSTRACT FROM AUTHOR]

Objective This research aimed to investigate the expression and mechanism of miR-155 and suppressor of cytokine signaling 1 (SOCS1) in rheumatoid arthritis (RA). Methods RT-PCR and flow cytometry were applied to detect the expression differences of miR-155, Th17, and Treg cells in peripheral blood of RA patients (RA group) and control group (HC group). Bioinformatics analysis and dual-luciferase reporter assay were conducted to investigate the regulatory relationship between miR-155 and SOCS1. CD4+T cells were isolated from peripheral blood of RA patients and transfected with miR-155 inhibitor, si-SOCS1, and their respective negative control sequences, and divided into four groups: miR-NC group, miR-155 inhibitor group, miR-155 inhibitor+ si-NC group, and miR-155 inhibitor+si-SOCS1 group. The cells were treated with Th17-inducing differentiation medium, and flow cytometry was used to determine the ratio of Th17 cells in each group of CD4+T cells. Western blot was used to determine the ratio of p-STAT3/STAT3 in the cells. Results Compared to the HC group, RA patients showed increased expression of miR-155 and Th17 ratio (P < 0.01), and decreased Treg cell ratio (P < 0.01). MiR-155 could target and inhibit the expression of SOCS1. Compared to the miR-NC group, the miR-155 inhibitor group, miR-155 inhibitor+si-NC group, and miR-155 inhibitor+si-SOCS1 group showed decreased Th17 ratio and p-STAT3/STAT3 ratio (P < 0.01). Compared to the miR-155 inhibitor group, the miR-155 inhibitor+ si-SOCS1 group exhibited increased Th17 ratio and p-STAT3/STAT3 ratio in CD4+T cells (P < 0.05). Conclusio through the SOCS1/STAT3 pathway, contributing to the imbalance of Th17/Treg cells in peripheral blood of RA patients. [ABSTRACT FROM AUTHOR]

Background: The current research examines the molecular terrain of celiac disease (CD) through microRNA (miRNA) and cytokines as potential new diagnostic and therapeutic markers. Gluten-appropriate immune response is a key feature of an autoimmune clinical entity known as CD that leads to inflammation and degeneration of small intestine mucosa. However, the mechanisms responsible for this remain unclear. Methods: Quantitative reverse transcription polymerase chain reaction (RT-qPCR ) was carried out on serum samples obtained from patients with CD and control groups to unravel their pathogenesis. Assessing miR-155, miR-15b, interleukin (IL)-2, IL-7, IL-35and IL-37 levels in expression might be useful in diagnosing or treating the disorder. Results: A significant dysregulation of these molecular players in patients with CD compared with healthy controls has been evidenced by results from this study. For instance, miR-155 was up-regulated, whereas miR-15b was significantly down-regulated in CD, illustrating their roles in immune responses and inflammation-mediated processes. Besides, there was an over-expression of IL-2 and an under-expression of IL-37 in patients with CD, indicating these biomolecules' role in immuno-dysregulation and inflammatory process underlying CD. In addition, a positive correlation between IL-2 and miRNA 155 expression levels was observed in patients with CD, suggesting that they could be involved together with other cytokines, showing the interplay between immune response pathways and inflammatory cascades during CD pathogenesis. Conclusion: These molecular signature discoveries might result in new and revolutionary diagnostic modalities and molecular-targeted therapies for CD pathogenesis. When used with the scientific understanding of miRNAs and cytokines associated with CD pathophysiology, it creates a basis for personalized medicine based on the individualized molecular profile of all patients. This will undoubtedly increase the efficacy of CD treatment strategies. In brief, more research on molecular pathways' workings should be done to harness their potential in CD diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU). Methods: The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues. Results: Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats. Conclusion: Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of lomefloxacin combined with triamcinolone olone in the treatment of acute otitis media (AOM) in children and the effects on serum miR-203a and miR-155. Meth ods According to different treatment methods, 134 children with AOM in our hospital from June 2021 to June 2023 were divided into the control group and the combination group, with 67 cases in each group. The control group was treated with triamcinolone and the combination group was treated with lomefloxacin anc triamcinolone. The clinical efficacy, recovery time, inflammatory factors [interleukin-8 (IL-8), procalcitonin (PCT), tumor necrosis factor(TNF-a)], serum levels of miR-203a and miR-155, pathogenic bacteria clearanc and adverse reactions were compared between the two groups. Results The total effective rate of combinee group [92.54% * (62/67)] was higher than that of control group [80.6% * (54/67)] the difference was statisti cally significant (P < 0.05) Compared with the control group, the hearing recovery time, tympanic congestion fading time earache fading time and fever fading time of the combined group were shorter after treatment, the difference were statistically significant (P < 0.05) Compared with before treatment. IL-8, TNF-a, PCT, miR 155 and miR-203a in the combination group were significantly decreased after treatment P < 0.05 ) The path ogenic bacteria clearance rate of the combined group [91.04% (61/67)] was higher than that of the contro group [77.61%(52/67)], the difference was statistically significant (P < 0.05), and there was no significan difference in the total incidence of adverse reactions between the two groups (P > 0.05) . Conclusion Lome floxacin combined with triamcinolone in the treatment of AOM is effective, can reduce inflammation by down. regulating the levels of miR-203a and miR-155, can also improve the clearance rate of pathogenic bacteria, pro mote disease recovery, and has high safety. [ABSTRACT FROM AUTHOR]

The role of adipose mesenchymal stem cells (Ad-MSCs) in metabolic syndrome remains unclear. We aimed to assess the expression of selected microRNAs in Ad-MSCs of non-diabetic adults in relation to Ad-MSC secretion of protein regulators and basic metabolic parameters. Ten obese, eight overweight, and five normal weight subjects were enrolled: 19 females and 4 males; aged 43.0 ± 8.9 years. Ad-MSCs were harvested from abdominal subcutaneous fat. Ad-MSC cellular expressions of four microRNAs (2−ΔCt values) and concentrations of IL-6, IL-10, VEGF, and IGF-1 in the Ad-MSC-conditioned medium were assessed. The expressions of miR-21, miR-122, or miR-192 did not correlate with clinical parameters (age, sex, BMI, visceral fat, HOMA-IR, fasting glycemia, HbA1c, serum lipids, CRP, and eGFR). Conversely, the expression of miR-155 was lowest in obese subjects (3.69 ± 2.67 × 10−3 vs. 7.07 ± 4.42 × 10−3 in overweight and 10.25 ± 7.05 × 10−3 in normal weight ones, p = 0.04). The expression of miR-155 correlated inversely with BMI (sex-adjusted r = −0.64; p < 0.01), visceral adiposity (r = −0.49; p = 0.03), and serum CRP (r = −0.63; p < 0.01), whereas it correlated positively with serum HDL cholesterol (r = 0.51; p = 0.02). Moreover, miR-155 synthesis was associated marginally negatively with Ad-MSC secretion of IGF-1 (r = −0.42; p = 0.05), and positively with that of IL-10 (r = 0.40; p = 0.06). Ad-MSC expression of miR-155 appears blunted in visceral obesity, which correlates with Ad-MSC IGF-1 hypersecretion and IL-10 hyposecretion, systemic microinflammation, and HDL dyslipidemia. Ad-MSC studies in metabolic syndrome should focus on miR-155. [ABSTRACT FROM AUTHOR]

Background: Hypertrophy of the ligamentum flavum (HLF) is a common contributor to spinal stenosis which results in significant neurological impairments. Circular RNA (circRNA) circ_0003609 has been linked to HLF; however, the exact mechanism by which it causes this disease is unclear. Methods: Circ_0003609 expressions were regulated in HLF cells by overexpression vectors and RNA interference. Cell proliferation and fibrosis-related gene expression were checked by the Cell Counting Kit-8 (CCK-8) assay and western blotting. CircBank's prediction of the association between miR-155 and circ_0003609 was supported by a dual-luciferase reporter experiment. The function of the miR-155/sirtuin 1 (SIRT1) axis in controlling HLF fibrosis was further examined. Results: Overexpression of circ_0003609 suppressed HLF cell propagation and fibrosis compared to its silencing. It was found that circ_0003609 served as the sponge for miR-155 and that the circ_0003609/miR-155 axis controlled the fibrosis of HLF cells. It was found that circ_0003609 acted as a sponge for miR-155, regulating the fibrosis of HLF cells. Further, miR-155 targets SIRT1, and the miR-155/SIRT1 axis promotes HLF cell fibrosis. Conclusion: Circ_0003609 ameliorates hypertrophied ligamentum flavum (LF) by modulating the miR-155/SIRT1 axis, indicating a potential treatment approach for HLF. [ABSTRACT FROM AUTHOR]

Background: Micro RNA155 (miR-155) was identified as an essential determinant in immunological responses, and its genetic variants have increasing attention due to their ability to modulate its expression and potentially influence the susceptibility to autoimmune illnesses including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, etc. Objectives: To examine the impact of miR-155 gene polymorphism (rs767649A>T) and miR-155 gene expression and their association with multiple sclerosis (MS) in a sample of Iraqi patients. Materials and methods: A total of 75 blood specimens were obtained from individuals diagnosed with MS. While an additional 75 blood specimens were collected from evidently healthy participants serving as a control group, with an age ranged 20-71 years. miR-155 gene polymorphism (rs767649 A>T) was determined utilizing Tetra-ARMS Polymerase Chain Reaction (Tetra-ARMS PCR) and miR-155 expression was evaluated using Real-time Polymerase Chain Reaction (RT-PCR). Results: The females experienced MS at a higher rate (69.33%) compared to the males. Furthermore, the age group 30-39 years showed a greater susceptibility to the disease (54.67%). The analysis of miR-155 (rs767649 A>T) SNP in MS patients indicated that 7 (9.34%) had the wild genotype (AA), 31 (41.33%) had the heterogeneous genotype (AT), and 37 (49.33%) had the mutant genotype (TT). These differences were statistically significant (P-value = 0.040). A allele frequency was 45 (0.3) (OR: 0.25; CI: 0.15-0.41) and T allele frequency was 105 (0.7) (OR: 3.91; CI: 2.42-6.33) in MS patients. While analysis of miR-155 gene expression demonstrated a significant increase in the patient group (1.82 ± 0.25 fold) compared to the healthy control group (0.33 ± 0.13 fold). The relationship between miR-155 gene expression and miR-155 genotypes in MS patients, revealed a notable elevation in miR-155 gene expression at the TT genotype (3.15 ± 0.73 fold), followed by TA genotype (1.29 ±0.65fold) and finally AA genotype (0.37 ± 0.19 fold) with highly statistically significant difference (P-value = 0.001). Conclusion: There was a significant positive correlation between miR-155 (rs767649 A>T) genotypes and miR-155 expression and susceptibility to MS in Iraqi patients. These findings suggests that miR-155 may hold potential as a diagnostic and therapeutic marker for the disease. [ABSTRACT FROM AUTHOR]

The NFE2L2 gene of the redox-sensitive transcription factor NRF2 is a target of miR-155 microRNA. In the present work, a transfection of miR-155 imitator (mimic) was performed into dacarbazine-resistant B16 melanoma cells. It was determined that, under the influence of miR-155 microRNA mimic, the expression level of NRF2 encoded by the NFE2L2 decreases in melanoma cells both in conditions of oxidative stress and without it. A decrease in the level of NRF2 was accompanied by a decrease in the viability of dacarbazine-resistant melanoma cells. Thus, miR-155-mediated activation of NRF2, which regulates the intensity of antioxidant processes in the cell, can be associated with the preservation of viability and development of drug resistance of tumor cells. The latter can be used to overcome chemoresistance in the treatment of oncological diseases. [ABSTRACT FROM AUTHOR]

Abstract Incident chronic kidney disease (CKD) varies in populations with hypertension of similar severity. Proteinuria promotes CKD progression in part due to activation of plasminogen to plasmin in the podocytes, resulting in oxidative stress‐mediated injury. Additional mechanisms include deficiency of renal alpha‐klotho, that inhibits Wnt/beta‐catenin, an up regulator of intra‐renal renin angiotensin system (RAS) genes. Alpha‐klotho deficiency therefore results in upregulation of the intra‐renal RAS via Wnt/beta‐catenin. In hypertensive, Dahl salt sensitive (DS) and spontaneously hypertensive rats (SHR), we investigated renal and vascular injury, miR‐155, AT1R, alpha‐klotho, and TNF‐α. Hypertensive high salt DS (DS‐HS), but not SHR developed proteinuria, plasminuria, and glomerulosclerosis. Compared to DS low salt (DS‐LS), in hypertensive DS‐HS alpha‐klotho decreased 5‐fold in serum and 2.6‐fold in kidney, whereas serum mir‐155 decreased 3.3‐fold and AT1R increased 52% in kidney and 77% in aorta. AT1R, alpha‐klotho, and miR‐155 remained unchanged in prehypertensive and hypertensive SHR. TNF‐α increased by 3‐fold in serum and urine of DS‐HS rats. These studies unveiled in salt sensitive DS‐HS, but not in SHR, a genetically conditioned dysfunction of the intermolecular network integrated by alpha‐klotho, RAS, miR‐155, and TNF‐α that is at the helm of their end‐organ susceptibility while plasminuria may participate as a second hit.

Background Ineffective erythropoiesis (IE) is the primary cause of anemia and associated pathologies in β-thalassemia. The characterization of IE is imbalance of erythroid proliferation and differentiation, resulting in increased erythroblast proliferation that fails to differentiate and gives rise to enucleate RBCs. MicroRNAs (miRs) are known to play important roles in hematopoiesis. miR-155 is a multifunctional molecule involved in both normal and pathological hematopoiesis, and its upregulation is observed in patients with β-thalassemia/HbE. However, the expression and function of miR-155, especially in β-thalassemia, have not yet been explored. Methods To study miR-155 expression in thalassemia, erythroblast subpopulations, CD45-CD71+Ter-119+ and CD45-CD71−Ter-119+ were collected from βIVSII-654 thalassemic bone marrow. Additionally, a two-phase culture of mouse bone marrow erythroid progenitor cells was performed. Expression of miR-155 and predicted mRNA target genes, c-myc, bach-1 and pu-1, were determined by quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and normalized to small nucleolar RNA (snoRNA) 202 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively. To investigate the effect of miR-155 expression, erythroblasts were transfected with miR-inhibitor and -mimic in order to elevate and eliminate miR-155 expression, respectively. Erythroid cell differentiation was evaluated by Wright–Giemsa staining and flow cytometry. Results miR-155 was upregulated, both in vivo and in vitro, during erythropoiesis in β-thalassemic mice. Our study revealed that gain- and loss of function of miR-155 were involved in erythroid proliferation and differentiation, and augmented proliferation and differentiation of thalassemic mouse erythroblasts may be associated with miR-155 upregulation. miR-155 upregulation in β-thalassemic mice significantly increased the percentage of basophilic and polychromatic erythroblasts. Conversely, a significant decrease in percentage of basophilic and polychromatic erythroblasts was observed in β-thalassemic mice transfected with anti-miR-155 inhibitor. We also examined the mRNA targets (c-myc, bach-1 and pu-1) of miR-155, which indicated that c-myc is a valid target gene of miR-155 that regulates erythroid differentiation. Conclusion miR-155 regulates IE in β-thalassemia via c-myc expression controlling erythroblast proliferation and differentiation.

Keratitis induced by Pseudomonas aeruginosa (P. aeruginosa) is an acute and serious corneal inflammation. As a family of gene regulators, miRNAs play a crucial role in modulating host response after microbial invasion. However, their functions in P. aeruginosa keratitis remain largely unclear. In the present study, we demonstrated that miR-155 expression was significantly increased in macrophages and corneal tissue after P. aeruginosa infection. In vivo studies demonstrated that mice with miR-155 knockdown displayed more resistance to P. aeruginosa keratitis, with a lower bacterial burden. In addition, in vitro and in vivo studies indicated that miR-155 enhanced apoptosis of macrophages after P. aeruginosa infection, and resulted in a susceptible phenotype of P. aeruginosa keratitis. Moreover, miR-155 induced apoptosis through reducing activation of PI3K-Akt signaling pathway. Our data provided evidence of miR-155 mediated apoptosis of macrophage in P. aeruginosa keratitis, which may be an underlying target for the therapy of P. aeruginosa keratitis and other infectious diseases.