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Dermatology Reports Jun 2024Acne (syn. acne vulgaris) is a common inflammatory skin disorder associated with puberty and adolescence. The disease is characterized by comedoneous lesions, papules,...
Acne (syn. acne vulgaris) is a common inflammatory skin disorder associated with puberty and adolescence. The disease is characterized by comedoneous lesions, papules, pustules, and nodules that are mostly found on the face. These lesions are caused by intricate interactions between the pilosebaceous unit and the () bacteria. Unhealthy acne and its aftereffects, like pigment changes and scarring, have a detrimental impact on one's quality of life. Recent years have seen a sharp increase in the approval of nucleic acid therapies (NATs), such as antisense oligonucleotides and short-interfering RNA medications, for rare diseases for which there are few or no effective treatments. These developments suggest that NATs may be useful in acne treatment plans down the road, as do clinical trials for microRNA (miRNA) modulation in skin contexts. We highlight promising miRNA targets for anti-acne therapy in this review. We outline the pathophysiology of acne in brief and emphasize the functions of . Next, we concentrate on the distinct impacts of biofilm and planktonic on a Toll-like receptor 2 axis that spans miR-146a-5p, which was recently discovered. Before discussing the potential contributions of miR-21-5p, miR-233-3p, and miR-150-5p to inflammatory axes in acne, we evaluate miR-146a-5p in sebocytes. Finally, we address patient involvement in miRNA-related acne research and translational perspectives.
PubMed: 38957637
DOI: 10.4081/dr.2024.9902 -
Frontiers in Immunology 2024Sepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate...
Exosome-shuttled miR-150-5p from LPS-preconditioned mesenchymal stem cells down-regulate PI3K/Akt/mTOR pathway via Irs1 to enhance M2 macrophage polarization and confer protection against sepsis.
RATIONALE
Sepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate inflammation during sepsis, and the preconditioning of MSCs could enhance their paracrine potential. Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms.
METHODS
Exosomes were isolated and characterized from the supernatants of MSCs. The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model. Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the studies, and to explain the potential mechanisms.
RESULTS
LPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo. , LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation. miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150-5p in LPS-Exo compared to that in Exo, and exosomal miR-150-5p was transferred into recipient macrophages and mediated macrophage polarization. Further investigation demonstrated that miR-150-5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway.
CONCLUSION
The current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150-5p as a novel molecular target for regulating immune hyperactivation during sepsis.
Topics: MicroRNAs; Animals; Exosomes; Mesenchymal Stem Cells; Sepsis; TOR Serine-Threonine Kinases; Mice; Proto-Oncogene Proteins c-akt; Lipopolysaccharides; Macrophages; Insulin Receptor Substrate Proteins; Signal Transduction; Phosphatidylinositol 3-Kinases; Male; Mice, Inbred C57BL; Macrophage Activation; Disease Models, Animal
PubMed: 38957471
DOI: 10.3389/fimmu.2024.1397722 -
Journal of Immunology Research 2024Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with...
BACKGROUND
Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research.
MATERIALS AND METHODS
A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein-protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes.
RESULTS
Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-B signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene.
CONCLUSIONS
Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.
Topics: Humans; Graft Rejection; Kidney Transplantation; Macrophages; Animals; Child; Rats; Receptors, CCR7; Protein Interaction Maps; CD48 Antigen; Gene Expression Profiling; Biomarkers; Computational Biology; Male; Gene Regulatory Networks; Databases, Genetic; Gene Ontology; Disease Models, Animal; Female; MicroRNAs
PubMed: 38957433
DOI: 10.1155/2024/6908968 -
Journal of Cellular and Molecular... Jul 2024Bone non-union is a common fracture complication that can severely impact patient outcomes, yet its mechanism is not fully understood. This study used differential...
Bone non-union is a common fracture complication that can severely impact patient outcomes, yet its mechanism is not fully understood. This study used differential analysis and weighted co-expression network analysis (WGCNA) to identify susceptibility modules and hub genes associated with fracture healing. Two datasets, GSE125289 and GSE213891, were downloaded from the GEO website, and differentially expressed miRNAs and genes were analysed and used to construct the WGCNA network. Gene ontology (GO) analysis of the differentially expressed genes showed enrichment in cytokine and inflammatory factor secretion, phagocytosis, and trans-Golgi network regulation pathways. Using bioinformatic site prediction and crossover gene search, miR-29b-3p was identified as a regulator of LIN7A expression that may negatively affect fracture healing. Potential miRNA-mRNA interactions in the bone non-union mechanism were explored, and miRNA-29-3p and LIN7A were identified as biomarkers of skeletal non-union. The expression of miRNA-29b-3p and LIN7A was verified in blood samples from patients with fracture non-union using qRT-PCR and ELISA. Overall, this study identified characteristic modules and key genes associated with fracture non-union and provided insight into its molecular mechanisms. Downregulated miRNA-29b-3p was found to downregulate LIN7A protein expression, which may affect the healing process after fracture in patients with bone non-union. These findings may serve as a prognostic biomarker and potential therapeutic target for bone non-union.
Topics: Humans; MicroRNAs; Biomarkers; Gene Regulatory Networks; Fracture Healing; Gene Expression Profiling; Computational Biology; Female; Male; Gene Ontology; Gene Expression Regulation; Fractures, Ununited; Middle Aged
PubMed: 38957040
DOI: 10.1111/jcmm.18522 -
Journal of Cellular and Molecular... Jul 2024This research explores the role of microRNA in senescence of human endothelial progenitor cells (EPCs) induced by replication. Hsa-miR-134-5p was found up-regulated in...
This research explores the role of microRNA in senescence of human endothelial progenitor cells (EPCs) induced by replication. Hsa-miR-134-5p was found up-regulated in senescent EPCs where overexpression improved angiogenic activity. Hsa-miR-134-5p, which targeted transforming growth factor β-activated kinase 1-binding protein 1 (TAB1) gene, down-regulated TAB1 protein, and inhibited phosphorylation of p38 mitogen-activated protein kinase (p38) in hsa-miR-134-5p-overexpressed senescent EPCs. Treatment with siRNA specific to TAB1 (TAB1si) down-regulated TAB1 protein and subsequently inhibited p38 activation in senescent EPCs. Treatment with TAB1si and p38 inhibitor, respectively, showed angiogenic improvement. In parallel, transforming growth factor Beta 1 (TGF-β1) was down-regulated in hsa-miR-134-5p-overexpressed senescent EPCs and addition of TGF-β1 suppressed the angiogenic improvement. Analysis of peripheral blood mononuclear cells (PBMCs) disclosed expression levels of hsa-miR-134-5p altered in adult life, reaching a peak before 65 years, and then falling in advanced age. Calculation of the Framingham risk score showed the score inversely correlates with the hsa-miR-134-5p expression level. In summary, hsa-miR-134-5p is involved in the regulation of senescence-related change of angiogenic activity via TAB1-p38 signalling and via TGF-β1 reduction. Hsa-miR-134-5p has a potential cellular rejuvenation effect in human senescent EPCs. Detection of human PBMC-derived hsa-miR-134-5p predicts cardiovascular risk.
Topics: MicroRNAs; Humans; Endothelial Progenitor Cells; Cellular Senescence; Leukocytes, Mononuclear; Middle Aged; Adaptor Proteins, Signal Transducing; Male; Cardiovascular Diseases; p38 Mitogen-Activated Protein Kinases; Female; Aged; Neovascularization, Physiologic; Transforming Growth Factor beta1; Adult; Risk Factors
PubMed: 38957039
DOI: 10.1111/jcmm.18523 -
Journal of Neuroinflammation Jul 2024Deposition of amyloid β, which is produced by amyloidogenic cleavage of APP by β- and γ-secretase, is one of the primary hallmarks of AD pathology. APP can also be...
BACKGROUND
Deposition of amyloid β, which is produced by amyloidogenic cleavage of APP by β- and γ-secretase, is one of the primary hallmarks of AD pathology. APP can also be processed by α- and γ-secretase sequentially, to generate sAPPα, which has been shown to be neuroprotective by promoting neurite outgrowth and neuronal survival, etc. METHODS: The global expression profiles of miRNA in blood plasma samples taken from 11 AD patients as well as from 14 age and sex matched cognitively normal volunteers were analyzed using miRNA-seq. Then, overexpressed miR-140 and miR-122 both in vivo and in vitro, and knock-down of the endogenous expression of miR-140 and miR-122 in vitro. Used a combination of techniques, including molecular biology, immunohistochemistry, to detect the impact of miRNAs on AD pathology.
RESULTS
In this study, we identified that two miRNAs, miR-140-3p and miR-122-5p, both targeting ADAM10, the main α-secretase in CNS, were upregulated in the blood plasma of AD patients. Overexpression of these two miRNAs in mouse brains induced cognitive decline in wild type C57BL/6J mice as well as exacerbated dyscognition in APP/PS1 mice. Although significant changes in APP and total Aβ were not detected, significantly downregulated ADAM10 and its non-amyloidogenic product, sAPPα, were observed in the mouse brains overexpressing miR-140/miR-122. Immunohistology analysis revealed increased neurite dystrophy that correlated with the reduced microglial chemotaxis in the hippocampi of these mice, independent of the other two ADAM10 substrates (neuronal CX3CL1 and microglial TREM2) that were involved in regulating the microglial immunoactivity. Further in vitro analysis demonstrated that both the reduced neuritic outgrowth of mouse embryonic neuronal cells overexpressing miR-140/miR-122 and the reduced Aβ phagocytosis in microglia cells co-cultured with HT22 cells overexpressing miR-140/miR-122 could be rescued by overexpressing the specific inhibitory sequence of miR-140/miR-122 TuD as well as by addition of sAPPα, rendering these miRNAs as potential therapeutic targets.
CONCLUSIONS
Our results suggested that neuroprotective sAPPα was a key player in the neuropathological progression induced by dysregulated expression of miR-140 and miR-122. Targeting these miRNAs might serve as a promising therapeutic strategy in AD treatment.
Topics: MicroRNAs; Animals; Alzheimer Disease; Mice; Humans; Microglia; Mice, Inbred C57BL; Male; Chemotaxis; Female; ADAM10 Protein; Amyloid Precursor Protein Secretases; Mice, Transgenic; Aged; Gene Expression Regulation
PubMed: 38956605
DOI: 10.1186/s12974-024-03162-z -
Molecular Brain Jul 2024Glioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol... (Review)
Review
Glioblastoma (GBM) is an aggressive nervous system tumor with a poor prognosis. Although, surgery, radiation therapy, and chemotherapy are the current standard protocol for GBM patients, there is still a poor prognosis in these patients. Temozolomide (TMZ) as a first-line therapeutic agent in GBM can easily cross from the blood-brain barrier to inhibit tumor cell proliferation. However, there is a high rate of TMZ resistance in GBM patients. Since, there are limited therapeutic choices for GBM patients who develop TMZ resistance; it is required to clarify the molecular mechanisms of chemo resistance to introduce the novel therapeutic targets. MicroRNAs (miRNAs) regulate chemo resistance through regulation of drug metabolism, absorption, DNA repair, apoptosis, and cell cycle. In the present review we discussed the role of miRNAs in TMZ response of GBM cells. It has been reported that miRNAs mainly induced TMZ sensitivity by regulation of signaling pathways and autophagy in GBM cells. Therefore, miRNAs can be used as the reliable diagnostic/prognostic markers in GBM patients. They can also be used as the therapeutic targets to improve the TMZ response in GBM cells.
Topics: Humans; Temozolomide; Glioblastoma; MicroRNAs; Drug Resistance, Neoplasm; Brain Neoplasms; Animals; Dacarbazine; Autophagy; Gene Expression Regulation, Neoplastic
PubMed: 38956588
DOI: 10.1186/s13041-024-01113-6 -
BMC Women's Health Jul 2024Breast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper...
BACKGROUND
Breast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper once again confirmed the efficacy of lncRNA in tumor regulation by introducing the mechanism of the diagnosis of breast cancer by the MIR497HG/miR-16-5p axis.
METHODS
The abnormal expression of MIR497HG in breast cancer was determined by RT-qPCR method, and the correlation between MIR497HG expression and clinicopathological characteristics of breast cancer patients was analyzed via Chi-square test. To understand the diagnostic potential of MIR497HG in breast cancer by drawing the receiver operating characteristic curve (ROC). The overexpressed MIR497HG (pcDNA3.1-MIR497HG) was designed and constructed to explore the regulation of elevated MIR497HG on biological function of BT549 and Hs 578T cells through Transwell assays. Additionally, the luciferase gene reporter assay and Pearson analysis evaluated the targeting relationship of MIR497HG to miR-16-5p.
RESULTS
MIR497HG was decreased in breast cancer and had high diagnostic function, while elevated MIR497HG inhibited the migration and invasion of BT549 and Hs 578T cells. In terms of functional mechanism, miR-16-5p was the target of MIR497HG, and MIR497HG reversely regulated the miR-16-5p. miR-16-5p mimic reversed the effects of upregulated MIR497HG on cell biological function.
CONCLUSIONS
In general, MIR497HG was decreased in breast cancer, and the MIR497HG/miR-16-5p axis regulated breast cancer tumorigenesis, providing effective insights for the diagnosis of patients.
Topics: Humans; MicroRNAs; Female; Breast Neoplasms; RNA, Long Noncoding; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Movement; Middle Aged; Cell Proliferation
PubMed: 38956558
DOI: 10.1186/s12905-024-03208-7 -
BMC Cancer Jul 2024MicroRNA-1 (miR-1) is a tumour suppressor that can inhibit cell proliferation and invasion in several cancer types. In addition, miR-1 was found to be associated with...
BACKGROUND
MicroRNA-1 (miR-1) is a tumour suppressor that can inhibit cell proliferation and invasion in several cancer types. In addition, miR-1 was found to be associated with drug sensitivity. Circulating miRNAs have been proven to be potential biomarkers with predictive and prognostic value. However, studies of miR-1 expression in the serum of breast cancer (BC) patients are relatively scarce, especially in patients receiving neoadjuvant chemotherapy (NAC).
METHODS
Serum samples from 80 patients were collected before chemotherapy, and RT-PCR was performed to detect the serum expression of miR-1. The correlation between miR-1 expression in serum and clinicopathological factors, including pathological complete response (pCR), was analyzed by the chi-squared test and logistic regression. KEGG and GSEA analysis were also performed to determine the biological processes and signalling pathways involved.
RESULTS
The miR-1 high group included more patients who achieved a pCR than did the miR-1 low group (p < 0.001). Higher serum miR-1 levels showed a strong correlation with decreased ER (R = 0.368, p < 0.001) and PR (R = 0.238, p = 0.033) levels. The univariate model of miR-1 for predicting pCR achieved an AUC of 0.705 according to the ROC curve. According to the interaction analysis, miR-1 interacted with Ki67 to predict the NAC response. According to the Kaplan-Meier plot, a high serum miR-1 level was related to better disease-free survival (DFS) in the NAC cohort. KEGG analysis and GSEA results indicated that miR-1 may be related to the PPAR signalling pathway and glycolysis.
CONCLUSIONS
In summary, our data suggested that miR-1 could be a potential biomarker for pCR and survival outcomes in patients with BC treated with NAC.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; MicroRNAs; Biomarkers, Tumor; Middle Aged; Prognosis; Adult; Aged; Treatment Outcome; Gene Expression Regulation, Neoplastic; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38956544
DOI: 10.1186/s12885-024-12500-6 -
Cellular & Molecular Biology Letters Jul 2024Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis...
BACKGROUND
Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear.
METHODS
We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS's function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC.
RESULTS
We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes.
CONCLUSION
The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS's role in regulating angiogenesis and provides a novel target for EC treatment.
Topics: Humans; MicroRNAs; RNA, Long Noncoding; Neovascularization, Pathologic; Female; Gene Expression Regulation, Neoplastic; Animals; Cell Proliferation; Cell Line, Tumor; Endometrial Neoplasms; Cell Movement; Mice; Disease Progression; Mice, Nude; TRPM Cation Channels; Mice, Inbred BALB C; Prognosis; Angiogenesis
PubMed: 38956502
DOI: 10.1186/s11658-024-00612-7