Journal: Journal of Sport and Health Science

Article Title: Exercise training-induced extracellular miR-136-3p modulates glucose uptake and myogenesis through targeting of NRDC in human skeletal muscle

doi: 10.1016/j.jshs.2025.101091

Figure Lengend Snippet: NRDC is a direct target of miR-136-3p in human myotubes. Skeletal muscle NRDC mRNA is responsive to training and inactivity. (A) Tissue mRNA expression of NRDC from the Human Protein Atlas database showing enriched expression of NRDC in human skeletal muscle. (B) The miR-136-3p target site in the NRDC gene is highly conserved in mammals. (C) Luciferase activity in HEK293 cells co-transfected the NRDC 3’UTR and miR-136-3p with or without anti-miR136-3p inhibitors. miR-136-3p transfection downregulates NRDC (D) mRNA and (E) representative image of protein abundance in human myotubes. (F) Publicly available data ( GSE14413 ) showing NRDC mRNA expression in human skeletal muscle of healthy young participants after 6 weeks of endurance training ( n = 8). (G) Publicly available data ( GSE120862 ) showing NRDC mRNA expression in human skeletal muscle of healthy young participants after 2 months of aerobic training ( n = 10). (H) Publicly available data ( GSE14901 ) showing NRDC mRNA expression in human skeletal muscle of healthy young participants after 14 days of immobilization ( n = 24). * p < 0.05, ** p < 0.005. GSE = gene set enrichment; HEK293 = human embryonic kidney; miR = microRNA; NC = negative control; NRDC = nardilysin convertase; nTPM = normalized transcripts per million; si NRDC = small interfering RNA of NRDC ; UTR = untranslated region.

Article Snippet: MiR-136-3p was labeled with Cy3 using Silencer small interfering RNA (siRNA) Labeling Kit with Cy3 Dye (Thermo Fisher Scientific) and loaded into exosome-enriched EVs with Exo-Fect siRNA/miRNA Transfection Reagent (System Biosciences, Palo Alto, CA, USA).

Techniques: Expressing, Luciferase, Activity Assay, Transfection, Quantitative Proteomics, Negative Control, Small Interfering RNA

Journal: Journal of Sport and Health Science

Article Title: Exercise training-induced extracellular miR-136-3p modulates glucose uptake and myogenesis through targeting of NRDC in human skeletal muscle

doi: 10.1016/j.jshs.2025.101091

Figure Lengend Snippet: Cellular metabolism in human myotubes after miR-136-3p transfection or NRDC silencing. Mitochondrial respiration in miR-136-3p-transfected or NRDC- silenced human myotubes was monitored using the Mitochondrial Stress Test. (A) OCR and (B) ECAR were measured using the Seahorse XFe24 Extracellular Flux Analyzer. The trace shows representative data. (C) Quantification of the mitochondrial respiration data for basal respiration, maximal respiration, ATP production, and spare respiratory capacity obtained from 3 independent experiments. Human myotubes were transfected with miR-136-3p or siRNA against NRDC before determination of (D) uptake of radiolabeled glucose, (E) rates of radiolabeled glucose oxidation, (F) conversion of radiolabeled glucose into glycogen, (G) rate of radiolabeled palmitic acid oxidation, (H) protein synthesis as assessed by incorporation of puromycin, and (I) lactate release into the media. Results are expressed as mean ± standard error of the mean. * p < 0.05, ** p < 0.005 vs. control cells. ECAR = extracellular acidification rate; FCCP = carbonyl cyanide-p-trifluoromethoxyphenylhydrazone; miR = microRNA; NC = negative control; NRDC = nardilysin convertase; ns = no significance; OCR = oxygen consumption rate; OigoA = oligomycin A; Rot/AA = rotenone and antimycin A; si NRDC = small interfering RNA of NRDC; siRNA = small interfering RNA; scr = negative control for small interfering RNA.

Article Snippet: MiR-136-3p was labeled with Cy3 using Silencer small interfering RNA (siRNA) Labeling Kit with Cy3 Dye (Thermo Fisher Scientific) and loaded into exosome-enriched EVs with Exo-Fect siRNA/miRNA Transfection Reagent (System Biosciences, Palo Alto, CA, USA).

Techniques: Transfection, Control, Negative Control, Small Interfering RNA

Journal: Journal of Sport and Health Science

Article Title: Long-term aerobic exercise enhances circulating exosomal miR-214-3p to promote endothelial progenitor cell-mediated repair of endothelial damage induced by obesity

doi: 10.1016/j.jshs.2025.101094

Figure Lengend Snippet: Circulating exosomal miR-214-3p regulated the function of EPC in both humans and rats with obesity. (A and B) Targeted transcriptome sequencing of miRNAs within circulating exosomes derived from (A) humans and (B) rats unveiled the regulatory impact of aerobic exercise on miRNA expression profiles in these vesicles. The left panel shows a volcano plot of differentially expressed genes, and the right panel shows a heatmap representation of the transcriptome sequencing data, illustrating the expression patterns of differentially expressed genes in circulating exosomes. (C and D) qPCR was used to validate the relative expression levels of miR-214-3p in circulating exosomes derived from (C) humans ( n = 3 for each group; * p < 0.05, Exercise vs . Control) and (D) rats ( n : 6–12 for each group; * p < 0.05, HC vs . NC; # p < 0.05, HE vs . HC). (E) qPCR validation of miR-214-3p expression in miR-214-3p-overexpressing EPC ( n = 3 for each group). ** p < 0.01, miR-214-3p mimics vs . mimics NC; ## p < 0.01, miR-214-3p mimics vs . Control. (F) Summary data for cell vitality level among groups ( n : 10–12 for each group). *** p < 0.001, miR-214-3p mimics vs . mimics NC. (G and H) Summary data (G) and representative images (H) of wound healing in the scratch assay, showcasing the migration level of EPC among groups ( n = 4 for each group). * p < 0.05, miR-214-3p mimics vs . mimics NC. EPC = endothelial progenitor cells; HC = the high-fat diet with sedentary group; HE = the high-fat diet with exercise group; mimics NC = mimics negative control; miR = microRNA; NC = the normal diet with sedentary group; qPCR = quantitative polymerase chain reaction.

Article Snippet: Total RNAs from tissues, cells, and exosomes were extracted using Trizol (R0016; Beyotime Biotech, Shanghai, China), following the manufacturer’s recommendations. mRNA samples underwent reverse transcription using the Evo M-MLV Kit (AG11705; Accurate Biotechnology, Changsha, China), while miRNA samples were reversely transcribed using the All-in-OneTM miRNA qPCR Kit (QP115; iGene Biotechnology, Guangzhou, China), following the provided instructions.

Techniques: Sequencing, Derivative Assay, Expressing, Control, Biomarker Discovery, Wound Healing Assay, Migration, Negative Control, Real-time Polymerase Chain Reaction

Journal: Journal of Sport and Health Science

Article Title: Long-term aerobic exercise enhances circulating exosomal miR-214-3p to promote endothelial progenitor cell-mediated repair of endothelial damage induced by obesity

doi: 10.1016/j.jshs.2025.101094

Figure Lengend Snippet: miR-214-3p plays an essential role in exercise-mediated protection against obesity-induced EPC dysfunction in vivo . (A) Dynamic weight change curves of rats. After randomization at Week 10, rats underwent treadmill exercise until the end of Week 18 ( n : 5–7 for each group). * p < 0.05, KO + HE vs . WT + NC; ### p < 0.001, WT + HC vs . WT + NC; ††† p < 0.001, WT + HE vs . WT + NC; ‡‡‡ p < 0.001, WT + HE vs . WT + HC; §§ p < 0.01, KO + HE vs . WT + HE. (B) Summary data for Lee's index among groups at Week 10 and Week 18 ( n : 5–7 for each group). Left panel: ** p < 0.01, KO + HE vs . WT + NC; ### p < 0.001, WT + HC vs . WT + NC; ††† p < 0.001, WT + HE vs . WT + NC; Right panel: *** p < 0.001, KO + HE vs . WT + HC; ### p < 0.001, WT + HC vs . WT + NC; ‡‡‡ p < 0.001, WT + HE vs . WT + HC. (C) Summary data for acetylcholine (ACh)-induced, endothelium-dependent relaxation in mesenteric arteries among groups ( n : 5–6 for each group). * p < 0.05, WT + HE vs . KO + HE; # p < 0.05, ## p < 0.05, WT + HE vs . WT + HC. (D) Summary data for EC 50 values in mesenteric arteries among groups in response to ACh ( n : 5–6 for each group). * p < 0.05, KO + HE vs . WT + HE; ## p < 0.01, WT + HE vs . WT + HC; ‡‡ p < 0.01, WT + HC vs . WT + NC. (E) Cell proliferation assays demonstrated that exosomes derived from the WT + HC group exhibited a diminished capacity to promote EPC proliferation compared to the WT + NC group in rats. In contrast, exosomes derived from the WT + HE group significantly enhanced EPC proliferation, which was abolished by knocking out miR-214-3p in rats ( n = 10 for each group). *** p < 0.001, KO + HE vs . WT + HE; ### p < 0.001, WT + HE vs . WT + HC; ‡‡ p < 0.01, WT + HC vs . WT + NC. (F) Scratch assay results showed that exosomes derived from the WT + HC group exhibited a diminished capacity to enhance EPC migration rates compared to the WT + NC group in rats. In contrast, exosomes derived from the WT + HE group significantly enhanced EPC migration rates, which was abolished by knocking out miR-214-3p in rats ( n = 6 for each group). *** p < 0.001, KO + HE vs . WT + HE; ### p < 0.001, WT + HE vs . WT + HC; ‡‡ p < 0.01, WT + HC vs . WT + NC. (G) Representative images of wound healing in the scratch assay, showcasing the migratory response of rat EPC. (H) qPCR analyses of pre-miR-214-3p and miR-214-3p in tissues from obese rats with and without exercise training ( n : 4–6 for each group). *** p < 0.001, HE vs . HC. EC 50 = half maximal effective concentration; EPC = endothelial progenitor cells; HC = the high-fat diet with sedentary group; HE = the high-fat diet with exercise group; KO + HE = the knockout + high-fat diet with exercise group; miR = microRNA; pre-miR = precursor microRNA; WT + HC = the wild-type + high-fat diet with sedentary group; WT + HE = the wild-type + high-fat diet with exercise group; WT + NC = the wild-type + normal diet with sedentary group.

Article Snippet: Total RNAs from tissues, cells, and exosomes were extracted using Trizol (R0016; Beyotime Biotech, Shanghai, China), following the manufacturer’s recommendations. mRNA samples underwent reverse transcription using the Evo M-MLV Kit (AG11705; Accurate Biotechnology, Changsha, China), while miRNA samples were reversely transcribed using the All-in-OneTM miRNA qPCR Kit (QP115; iGene Biotechnology, Guangzhou, China), following the provided instructions.

Techniques: In Vivo, Derivative Assay, Wound Healing Assay, Migration, Concentration Assay, Knock-Out

Journal: Metabolism Open

Article Title: Non-coding RNAs in neurodegeneration: an axis-based, evidence-tiered mechanistic synthesis

doi: 10.1016/j.metop.2026.100458

Figure Lengend Snippet: Axis Proteostasis/homeostasis and pathological protein accumulation. ( A ) Representative miRNA nodes implicated in proteostasis collapse across neurodegenerative settings, highlighting links to amyloidogenic processing and stress signaling (e.g., miR-29/BACE1 in Aβ plaque burden; miR-146a–NF-κB signaling intersecting with tau-related pathology; and ALS-associated vulnerability aligned with impaired miRNA processing such as miR-218 depletion). ( B ) lncRNA-mediated regulation of proteostasis-related gene axis, emphasizing lncRNAs proposed to modulate amyloidogenic pathways and protein handling (e.g., BACE1-AS, NDM29, and 51A/SORL1-related mechanisms), as well as aggregation-relevant nodes reported in PD contexts (e.g., HOTAIR–miR-221-3p–α-synuclein-related phenotypes). ( C ) circRNA-linked regulatory motifs that converge on neuronal injury and proteostasis-adjacent clearance pathways, primarily via miRNA-coupled axes (e.g., circAXL/miR-328/BACE1; circLPAR1/miR-212-3p/ZNF217; and circBptf/miR-138-5p/p62/SQSTM1).

Article Snippet: Axis Proteostasis/homeostasis and pathological protein accumulation. ( A ) Representative miRNA nodes implicated in proteostasis collapse across neurodegenerative settings, highlighting links to amyloidogenic processing and stress signaling (e.g., miR-29/BACE1 in Aβ plaque burden; miR-146a–NF-κB signaling intersecting with tau-related pathology; and ALS-associated vulnerability aligned with impaired miRNA processing such as miR-218 depletion). ( B ) lncRNA-mediated regulation of proteostasis-related gene axis, emphasizing lncRNAs proposed to modulate amyloidogenic pathways and protein handling (e.g., BACE1-AS, NDM29, and 51A/SORL1-related mechanisms), as well as aggregation-relevant nodes reported in PD contexts (e.g., HOTAIR–miR-221-3p–α-synuclein-related phenotypes). ( C ) circRNA-linked regulatory motifs that converge on neuronal injury and proteostasis-adjacent clearance pathways, primarily via miRNA-coupled axes (e.g., circAXL/miR-328/BACE1; circLPAR1/miR-212-3p/ZNF217; and circBptf/miR-138-5p/p62/SQSTM1).

Techniques:

Journal: Metabolism Open

Article Title: Non-coding RNAs in neurodegeneration: an axis-based, evidence-tiered mechanistic synthesis

doi: 10.1016/j.metop.2026.100458

Figure Lengend Snippet: Axis II Neuroinflammation and glia-neuron crosstalk. ( A ) miRNA axis recurrently linked to inflammatory amplification and glial activation, illustrating representative nodes associated with cytokine signaling and microglial state shifts (e.g., miR-155 and pro-inflammatory cytokine outputs; let-7a_STAT3-related signaling; miR-124 as a homeostatic regulator; and miR-195/ROCK1-linked microglial activation). ( B ) lncRNAs positioned as inflammatory “state regulators” through transcriptional and post-transcriptional control, including examples frequently discussed in neurodegenerative inflammatory contexts (e.g., MALAT1 with IL-6/TNF-α profiles; NEAT1/miR-212-3p; and TUG1/miR-152-3p/PTEN signaling). ( C ) circRNA candidates proposed to tune innate immune signaling and glial polarization, highlighting representative axes such as circ_0000518 engaging FUS/CaMKKβ/AMPK pathways and M1 polarization, and circHIPK2 acting via miRNA sequestration with downstream receptor-linked stress responses (e.g., SIGMAR1-related signaling).

Article Snippet: Axis Proteostasis/homeostasis and pathological protein accumulation. ( A ) Representative miRNA nodes implicated in proteostasis collapse across neurodegenerative settings, highlighting links to amyloidogenic processing and stress signaling (e.g., miR-29/BACE1 in Aβ plaque burden; miR-146a–NF-κB signaling intersecting with tau-related pathology; and ALS-associated vulnerability aligned with impaired miRNA processing such as miR-218 depletion). ( B ) lncRNA-mediated regulation of proteostasis-related gene axis, emphasizing lncRNAs proposed to modulate amyloidogenic pathways and protein handling (e.g., BACE1-AS, NDM29, and 51A/SORL1-related mechanisms), as well as aggregation-relevant nodes reported in PD contexts (e.g., HOTAIR–miR-221-3p–α-synuclein-related phenotypes). ( C ) circRNA-linked regulatory motifs that converge on neuronal injury and proteostasis-adjacent clearance pathways, primarily via miRNA-coupled axes (e.g., circAXL/miR-328/BACE1; circLPAR1/miR-212-3p/ZNF217; and circBptf/miR-138-5p/p62/SQSTM1).

Techniques: Amplification, Activation Assay, Control

Journal: Metabolism Open

Article Title: Non-coding RNAs in neurodegeneration: an axis-based, evidence-tiered mechanistic synthesis

doi: 10.1016/j.metop.2026.100458

Figure Lengend Snippet: Axis IV Mitochondrial stress, oxidative injury, and autophagy-lysosome dynamics. ( A ) miRNA-linked pathways that connect mitochondrial quality control, autophagy regulation, and stress–inflammation coupling, highlighting representative nodes discussed in PD and related neurodegenerative contexts (e.g., miR-124 aligned with autophagy regulation; and miR-195/ROCK1-associated microglial activation as a mechanistic bridge between inflammation and cellular stress). ( B ) lncRNA candidates implicated in proteostasis–mitochondrial crosstalk through ubiquitination and lysosome/autophagy axis, illustrating examples such as lnc-ABCA12-3/UBQLN1-linked ubiquitination/autophagy pathways and lnc-HIBADH-4 miR-326 CTSD axes that converge on lysosomal protease activity and autophagy flux. ( C ) circRNA mediated tuning of mitochondrial homeostasis and mitophagy pathways, highlighting representative ceRNA-like motifs including circEPS15/miR-24-3p/PINK1–PRKN-dependent mitophagy, and circ016719/miR-29c/Map2k6-associated stress survival and apoptosis regulation. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Axis Proteostasis/homeostasis and pathological protein accumulation. ( A ) Representative miRNA nodes implicated in proteostasis collapse across neurodegenerative settings, highlighting links to amyloidogenic processing and stress signaling (e.g., miR-29/BACE1 in Aβ plaque burden; miR-146a–NF-κB signaling intersecting with tau-related pathology; and ALS-associated vulnerability aligned with impaired miRNA processing such as miR-218 depletion). ( B ) lncRNA-mediated regulation of proteostasis-related gene axis, emphasizing lncRNAs proposed to modulate amyloidogenic pathways and protein handling (e.g., BACE1-AS, NDM29, and 51A/SORL1-related mechanisms), as well as aggregation-relevant nodes reported in PD contexts (e.g., HOTAIR–miR-221-3p–α-synuclein-related phenotypes). ( C ) circRNA-linked regulatory motifs that converge on neuronal injury and proteostasis-adjacent clearance pathways, primarily via miRNA-coupled axes (e.g., circAXL/miR-328/BACE1; circLPAR1/miR-212-3p/ZNF217; and circBptf/miR-138-5p/p62/SQSTM1).

Techniques: Control, Activation Assay, Ubiquitin Proteomics, Activity Assay