Background:Adult-onset Still's disease (AOSD) is a rare autoinflammatory condition characterized by high spiking fevers, arthralgia, typical rash, and systemic inflammation. Life-threatening complications, such as macrophage activation syndrome (MAS) and disseminated intravascular coagulation (DIC), may arise. Prompt recognition and intensive management are crucial for patient survival. This report presents a case of AOSD complicated by MAS and pre-DIC, accompanied by a review of the relevant literature. Case Presentation:A 22-year-old male presented with recurrent high-grade fever, generalized red rash, lymphadenopathy, splenomegaly, and knee arthralgia. He met the Yamaguchi criteria for AOSD and the Ravelli criteria for MAS, and was diagnosed with pre-DIC using the Chinese Diagnostic Scoring System for DIC (CDSS). Following diagnosis, the patient received a comprehensive medical regimen that included glucocorticoids, the JAK inhibitor tofacitinib, infusion of fresh frozen plasma, and supportive care, resulting in clinical improvement. At the 8-month follow-up evaluation, the patient's condition remained stable without any signs of progression. Conclusion:This case underscores the critical importance of early identification of MAS and pre-DIC in AOSD, and demonstrates that aggressive immunosuppressive and supportive therapy, implemented within a multidisciplinary framework, is essential to prevent progression to overt DIC and multi-organ failure.

BackgroundHypertension-induced cardiac fibrosis leads to heart failure. Large-conductance calcium-activated potassium (BK) channels regulate vascular tone, and their activation may mitigate fibrosis. This study explores the impact of BK channel activation on angiotensin II (Ang II)-induced hypertension and cardiac fibrosis and its effects on nuclear factor-kappa B (NFκB) signaling.MethodsMale C57BL/6 J mice were infused with Ang II for 4 weeks to induce hypertension and cardiac fibrosis. The BK channel activator BMS-191011 was administered via intraperitoneal injection. Cardiac tissue was analyzed using histology, Western blotting and qPCR. Single channel recordings were used to analyze the activation of BKα channels. A dihydroethidium (DHE) Assay was used to detect superoxide (ROS) production. Superoxide Dismutase (SOD) was measured using a colorimetric activity kit. In vitro, macrophages (RAW 264.7) were stimulated with Ang II, to detect NFκB activation and macrophage polarization.ResultsThe expression of BKα mRNA and protein abundance was decreased while markers of cardiac fibrosis (fibronectin, vimentin, αSMA and TGF-β) and ROS production were increased in the hearts of Ang II-induced hypertensive mice. In addition, macrophage infiltration was significantly increased along with inflammatory cytokines IFNγ, IL-6, IL-4, IL-10 and TNFα. The BK channel opener, BMS-191011, significantly reduced hypertension, cardiac fibrosis, and ROS production, but restored SOD in the hearts of Ang II-treated mice. In cultured macrophages, we found that Ang II increased inflammatory cytokines through NFκB-NLRP3-caspase-1 signaling. After Ang II treatment, BK channel activation inhibited NFκB, NLRP3 and caspase-1 expression. BK channel activation also suppressed NFκB-NLRP3 signaling, leading to reduced ROS accumulation and restored SOD activity.ConclusionBK channel activation reduces Ang II-induced hypertension and cardiac fibrosis by modulating oxidative stress, inflammation and macrophage polarization through the NFκB-NLRP3 pathway. These findings implicate BK channel activators as a potential novel therapeutic strategy for hypertensive cardiomyopathy.

Background: Maladaptive repair following acute kidney injury leads to CKD, but the underlying molecular drivers remain incompletely understood. Krüppel-like factor 5 (Klf5), a zinc finger transcription factor, is upregulated in kidney diseases. However, its role and regulation in post-injury kidney repair are unknown. Methods: Klf5 expression was analyzed in C57BL/6 mice after unilateral ischemia/reperfusion (I/R), repeated low-dose cisplatin (RLDC), and unilateral ureteral obstruction (UUO) in vivo, in human CKD biopsies, and in TGFβ-, TNFα, and RLDC-treated kidney proximal tubule cells in vitro. The role of Klf5 was investigated using Klf5 knockdown proximal tubular cells in vitro and proximal tubule-specific Klf5 knockout mouse model in vivo. To examine the regulation by nuclear factor-κB (NF-κB), p65 (RelA, a key component of the NF-κB complex) was specifically ablated from kidney proximal tubule cells in mice. Results: Klf5 was transcriptionally induced in renal proximal tubular cells in mouse models of maladaptive kidney repair and in human CKD biopsies. Proximal tubule-specific Klf5 knockout significantly reduced fibrosis, inflammation, dedifferentiation, and cellular senescence in post-injury kidneys, leading to improved kidney repair. Genetic or pharmacologic inhibition of NF-κB attenuated Klf5 expression and downstream fibrotic and inflammatory responses. NF-κB was further proved to transactivate Klf5 via promoter binding. Conclusions: The results demonstrated Klf5 as a critical mediator of maladaptive repair and CKD development after AKI. Mechanistically, Klf5 was transcriptionally up-regulated via NF-κB. Upon induction, Klf5 contributed to renal inflammation, senescence, and fibrosis, highlighting potential therapeutic targets.

Background:The implementation of COVID-19 control and prevention measures has significantly influenced the incidence rates of multiple notifiable infectious diseases. We aimed to investigate the epidemiological trends of notifiable infectious diseases in mainland China from 2020 to 2024, a period spanning both stringent interventions and their subsequent relaxation. Methods:We systematically analysed surveillance data from the National Center for Disease Control and Prevention (2020-2024). We excluded COVID-19, monkeypox, and neonatal tetanus to ensure methodological consistency and comparability. We classified the diseases into Class A, B, and C notifiable infectious diseases and further grouped them by transmission routes: intestinal, respiratory, sexually transmitted and blood-borne, vector-borne/zoonotic, and others. We focused on incidence rates, mortality rates, seasonal patterns, and trends to inform future prevention and control strategies. Results:Between 2020 and 2024, mainland China recorded 38 notifiable infectious diseases (excluding COVID-19, monkeypox, and neonatal tetanus). The average incidence rate was 734.8945/100 000, showing an upward trend. Class A notifiable infectious diseases were extremely rare, Class B encompassed 25 types and showed a rising trend with minimal seasonal variation, and Class C included 11 types. Class C notifiable infectious diseases incidence remained relatively low from 2020 to 2022, but rose sharply in 2023 after the relaxation of COVID-19 restrictions, maintaining elevated levels in 2024, with pronounced winter/spring peaks observed, especially in 2023-2024. Respiratory infectious diseases (RIDs) exhibited the highest incidence, while blood-borne and sexually transmitted infectious diseases accounted for over 90.35% of the deaths. Conclusions:In mainland China, strict COVID-19 measures between 2020 and 2022 significantly reduced the incidence of RIDs. However, after COVID-19 management was downgraded and restrictions were relaxed in early 2023, these diseases resurged, demonstrating a 'suppression-rebound' effect.

BACKGROUND AND OBJECTIVE:Obesity and metabolic syndrome impose chronic lipotoxic stress on hepatocytes, contributing to macrophage reprogramming and fibrosis progression in steatotic liver disease. However, how soluble hepatocyte-derived factors regulate Kupffer cell-hepatic stellate cell (HSC) crosstalk remains unclear. This study investigated the role of hepatocyte NAT10-mediated N4-acetylcytidine (ac4C) RNA modification and explored potential ac4C-dependent targets involved in this process. METHODS:Hepa1-6 cells were exposed to palmitic acid with or without NAT10 knockdown, and nd key findings were validated in primary mouse hepatocytes. Hepatocyte-conditioned media were applied to primary Kupffer cells and a Kupffer-HSC coculture system. ac4C-RIP-qPCR and mRNA stability assays were performed. Recombinant TGFβ1 was used for rescue analysis. In vivo, hepatocyte-specific NAT10 knockdown was achieved using AAV8-TBG-shNat10 in a high-fat diet plus fructose model. RESULTS:NAT10 knockdown reduced TGFβ1 secretion from lipotoxic hepatocytes without affecting cell viability. Conditioned media induced Spp1 and Lgals3 expression in Kupffer cells, which was attenuated by NAT10 silencing. In the Kupffer-HSC coculture system, Kupffer cells primed by lipotoxic hepatocyte-conditioned media markedly increased HSC activation, as indicated by elevated α-SMA and Collagen I expression. This effect was diminished when Kupffer cells were exposed to media from NAT10-deficient hepatocytes, and recombinant TGFβ1 partially restored HSC activation. Tgfb1 showed reduced ac4C enrichment and mRNA stability following Nat10 knockdown, suggesting that it is a NAT10-responsive ac4C-associated transcript under lipotoxic conditions. In vivo, hepatocyte-specific NAT10 knockdown reduced hepatic TGFβ1 levels, decreased CLEC4F+LGALS3+ pro-fibrotic Kupffer cells, and alleviated liver fibrosis. CONCLUSIONS:Hepatocyte NAT10-mediated ac4C regulation contributes to pro-fibrotic Kupffer-HSC crosstalk in steatotic liver disease, at least partly through TGFβ1-associated soluble hepatocyte-derived signaling.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and the elderly, with limited treatment options. Venenum bufonis (Vb), a traditional Chinese medicine, exhibits broad pharmacological activities including antiviral and anti-inflammatory effects, but its potential against RSV-induced pneumonia remains unclear. This study evaluates Vb's therapeutic effects and mechanisms in RSV-infected pneumonia and identifies its key active constituents. RSV pneumonia was induced in C57BL/6 mice via intranasal inoculation. Mice were treated with Vb or ribavirin intraperitoneally for five days. Lung pathology, viral gene, inflammatory cytokine gene expression, NLRP3 pathway activation, and immune cell infiltration were assessed using H&E staining, electron microscopy, RT-qPCR, immunohistochemistry, RNA sequencing and flow cytometry. The results demonstrated that Vb treatment significantly reduced lung tissue damage, mRNA levels of RSV-N protein, proinflammatory cytokines (TNF-α, IL-6) and type II interferon (IFN-γ), and enhanced the mRNA levels of type I interferons (IFN-α/β). Furthermore, Vb markedly decreased macrophage infiltration and suppressed mRNA expression of NLRP3, Caspase-1, and IL-1β in lung tissue, suggesting it may alleviate RSV pneumonia by inhibiting macrophage-driven inflammation and NLRP3 activation. Additionally, bufalin, cinobufagin, and resibufogenin were identified as likely bioactive constituents mediating Vb's therapeutic effects. This study provides a scientific basis for the potential application of Vb in the treatment of RSV-induced pneumonia.

[This corrects the article DOI: 10.1016/j.heliyon.2024.e35681.].

The ATP6V0A4 gene encodes the a4 subunit of vacuolar H+-ATPase (V-ATPase), which mediates hydrogen ion transport across the membrane. Previous studies have suggested that mutations in ATP6V0A4 consistently result in a loss of function, impairing the hydrogen ion transport efficacy of V-ATPase and leading to distal renal tubular acidosis and sensorineural hearing loss. Here, we identified a 32-year-old male patient and his father, both of whom harbored a heterozygous ATP6V0A4 p.V512L mutation and exhibited hypochloremic metabolic alkalosis, acidic urine, and hypokalemia. Through a series of protein structural analyses and functional experiments, the V512L mutation was confirmed as a gain-of-function mutation in the ATP6V0A4 gene. V512-a4 increased a4 subunit expression abundance by enhancing V512L-a4 stability and reducing its degradation, which in turn potentiated the capacity of V-ATPase to acidify the tubular lumen, leading to acidic urine and metabolic alkalosis. Through mutant V512L-a4 subunit structure-based virtual and experimental screening, we identified F351 (C25H26FN3O2S), a small-molecule inhibitor specifically targeting the V512L-a4 mutant. In conclusion, we identified a gain-of-function mutation in the ATP6V0A4 gene, broadening its phenotypic and mutational spectrum, and we provide valuable insights into potential therapeutic approaches for diseases associated with ATP6V0A4 mutations.

Autosomal dominant polycystic kidney disease (ADPKD) is marked by aberrant cell proliferation driven by cAMP-PKA and MAPK signaling pathways. EGR1, a transcription factor directly activated by the above two pathways, is critical in the over-proliferation of tumor cells, which share similarities with cystic epithelial cells in ADPKD. This study utilized in vitro cell models, three-dimensional (3D) cyst model, embryonic renal cystic model, and PKD mouse model to clarify the role of EGR1 in cyst development of ADPKD. We found the high expression and nuclear condensates of EGR1 in human ADPKD renal cyst epithelial cells and PKD mouse kidney tissue. Pharmacological inhibition of EGR1 retarded cyst enlargement in in vitro, ex vivo, and in vivo ADPKD models. Furthermore, EGR1 formed nuclear condensates with YAP1 and CBP via phase separation, leading to EGR1-specific transcriptional activation and upregulation of cell-cycle-related genes (e.g., CCND1, CCNE1, and CDK4/6), thus promoting abnormal renal cystic epithelial cell proliferation. Disruption of EGR1 phase separation significantly alleviated cyst growth in the forskolin-induced 3D spheroid model of mIMCD3 cells and MDCK cyst model. These findings demonstrate that phase separation-mediated EGR1 condensates facilitate renal cyst development in ADPKD.

ETHNOPHARMACOLOGICAL RELEVANCE:Ling-gui-zhu-gan (LGZG) decoction, a traditional Chinese medicinal formulation with a long-established history, is frequently utilized in the treatment of fluid retention disorders, with a particular focus on metabolic dysfunction-associated steatotic liver disease (MASLD). Although its clinical efficacy has been substantiated, the precise mechanisms underlying its therapeutic effects on MASLD remain inadequately understood. AIM OF THE STUDY:This study sought to elucidate the functional role and regulatory mechanisms of LGZG decoction in the treatment of MASLD. MATERIALS AND METHODS:A murine model of MASLD was induced through the administration of a high-fat diet (HFD), followed by intervention with LGZG decoction. The therapeutic efficacy of LGZG decoction in mice with MASLD was assessed through a comprehensive methodology, including triglyceride quantification, biochemical assays, hematoxylin-eosin staining, and oil red O staining. Additionally, dot blotting, methylated DNA immunoprecipitation sequencing, real-time quantitative polymerase chain reaction, western blotting, and immunofluorescence were employed to investigate the potential mechanisms of action of LGZG decoction in the context of MASLD. ALKBH1 knockdown or overexpression in AML12 cells was performed to verify the function of ALKBH1 on steatosis, and regulation of downstream targets. RESULTS:The administration of LGZG decoction markedly ameliorated hepatic steatosis in mice with MASLD and enhanced the expression of AlkB homolog 1 (ALKBH1). ALKBH1 serves as a demethylase for DNA N6-methyladenosine (6 mA), facilitating the demethylation of DNA 6 mA and playing a pivotal role in the regulation of 6 mA modifications. The study demonstrated that LGZG decoction significantly diminished DNA 6 mA modification by upregulating ALKBH1 expression. Furthermore, LGZG treatment led to a reduction in 6 mA methylation on the promoters of pleckstrin and Sec7 domain containing 4 (PSD4) and ribosomal protein S23 (RPS23), which subsequently resulted in increased expression of PSD4 and RPS23 at both mRNA and protein levels. In addition, protein levels of ALKBH1 and PSD4 were significantly reduced in AML12 cells with free fatty acid treatment. Overexpression of ALKBH1 led to a significant decrease in TG levels, whereas ALKBH1 knockdown resulted in a significant increase in TG levels in AML12 cells. Overexpression of ALKBH1 also enhanced PSD4 expression, while ALKBH1 knockdown significantly suppressed PSD4 level. CONCLUSIONS:The findings suggest that LGZG decoction represents an effective therapeutic strategy for MASLD, alleviating hepatic steatosis through the enhancement of ALKBH1-mediated 6 mA modification, reduction of 6 mA methylation on the PSD4 promoter, and upregulation of PSD4 expression.

Rheumatoid arthritis (RA) is a persistent autoimmune condition characterized by synovitis and joint damage. Recent findings suggest a potential link to abnormal lactate metabolism. This study aims to identify lactate metabolism-related genes (LMRGs) in RA and investigate their correlation with the molecular mechanisms of RA immunity. Data on the gene expression profiles of RA synovial tissue samples were acquired from the gene expression omnibus (GEO) database. The RA database was acquired by obtaining the common LMRDEGs, and selecting the gene collection through an SVM model. Conducting the functional enrichment analysis, followed by immuno-infiltration analysis and protein-protein interaction networks. The results revealed that as possible markers associated with lactate metabolism in RA, KCNN4 and SLC25A4 may be involved in regulating macrophage function in the immune response to RA, whereas GATA2 is involved in the immune mechanism of DC cells. In conclusion, this study utilized bioinformatics analysis and machine learning to identify biomarkers associated with lactate metabolism in RA and examined their relationship with immune cell infiltration. These findings offer novel perspectives on potential diagnostic and therapeutic targets for RA.

Nocardia farcinica is an aerobic gram-positive bacterium that is pathogenic to humans. It usually causes local and adjacent tissues’ diseases at the entry of infection (most commonly occur in the lungs, skin, or central nervous system), which can also spread to other organs through the bloodstream such as joints, kidneys, and liver. However, these infections are often seen as opportunistic that occur in immunocompromised patients. Here, we report for the first time two immunocompetent patients lacking evidence of local infections, with multiple lymph node enlargements and fever as main clinical manifestations, finally diagnosed as nocardiosis by Metagenomic Next-Generation Sequencing testing (mNGS) from formalin-fixed and paraffin-embedded (FFPE) lymph node tissue, after all the other standard tests were negative. Both patients recovered after receiving anti-nocardia therapies. These two cases indicates that in healthy population, there may be more potential nocardia infections than we expected. Multiple lymph node enlargements and fever suggest a possibility of nocardiosis, especially in patients with fever of unknown origin (FUO). mNGS detection from FFPE lymph node tissue is an accurate, reliable and traceable method for diagnosis of nocardiosis.

Osteopenia and osteoporosis are among the most common metabolic bone diseases and represent major public health problems, with sufferers having an increased fracture risk. Diabetes is one of the most common diseases contributing to osteopenia and osteoporosis. However, the mechanisms underlying diabetes-induced osteopenia and osteoporosis remain unclear. Bone reconstruction, including bone formation and absorption, is a dynamic process. Large-conductance Ca2+-activated K+ channels (BK channels) regulate the function of bone marrow-derived mesenchymal stem cells, osteoblasts, and osteoclasts. Our previous studies revealed the relationship between BK channels and the function of osteoblasts via various pathways under physiological conditions. In this study, we reported a decrease in the expression of BK channels in mice with diabetes-induced osteopenia. BK deficiency enhanced mitochondrial Ca2+ and activated classical PINK1 (PTEN induced putative kinase 1)-PRKN/Parkin (parkin RBR E3 ubiquitin protein ligase)-dependent mitophagy, whereas the upregulation of BK channels inhibited mitophagy in osteoblasts. Moreover, SLC25A5/ANT2 (solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 5), a critical inner mitochondrial membrane protein participating in PINK1-PRKN-dependent mitophagy, was also regulated by BK channels. Overall, these data identified a novel role of BK channels in regulating mitophagy in osteoblasts, which might be a potential target for diabetes-induced bone diseases.

Exposure to particulate matter (PM) can cause airway inflammation and worsen various airway diseases. However, the underlying molecular mechanism by which PM triggers airway inflammation has not been completely elucidated, and effective interventions are lacking. Our study revealed that PM exposure increased the expression of histone deacetylase 9 (HDAC9) in human bronchial epithelial cells and mouse airway epithelium through the METTL3/m6A 6 A methylation/IGF2BP3 pathway. Functional assays showed that HDAC9 upregulation promoted PM-induced airway inflammation and activation of MAPK signaling pathway in vitro and in vivo. . Mechanistically, HDAC9 modulated the deacetylation of histone 4 acetylation at K12 (H4K12) in the promoter region of dual specificity phosphatase 9 (DUSP9) to repress the expression of DUSP9 and resulting in the activation of MAPK signaling pathway, thereby promoting PM-induced airway inflammation. Additionally, HDAC9 bound to MEF2A to weaken its anti-inflammatory effect on PM-induced airway inflammation. Then, we developed a novel inhaled lipid nanoparticle system for delivering HDAC9 siRNA to the airway, offering an effective treatment for PM-induced airway inflammation. Collectively, we elucidated the crucial regulatory mechanism of HDAC9 in PM-induced airway inflammation and introduced an inhaled therapeutic approach targeting HDAC9. These findings contribute to alleviating the burden of various airway diseases caused by PM exposure.

Oxidative stress and endoplasmic reticulum stress (ERS) was associated with the development of asthma. Edaravone (EDA) plays a classical role to prevent the occurrence and development of oxidative stress-related diseases. Herein, we investigated the involvement and signaling pathway of EDA in asthma, with particular emphasis on its impact on type 2 innate lymphoid cells (ILC2) and CD4+T cells, and then further elucidated whether EDA could inhibit house dust mite (HDM)-induced allergic asthma by affecting oxidative stress and ERS. Mice received intraperitoneally injection of EDA (10 mg/kg, 30 mg/kg), dexamethasone (DEX) and N-acetylcysteine (NAC), with the latter two used as positive control drugs. DEX and high dose of EDA showed better therapeutic effects in alleviating airway inflammation and mucus secretion in mice, along with decreasing eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) than NAC. Further, the protein levels of IL-33 in lung tissues were inhibited by EDA, leading to reduced activation of ILC2s in the lung. EDA treatment alleviated the activation of CD4+ T cells in lung tissues of HDM-induced asthmatic mice and reduced Th2 cytokine secretion in BALF. ERS-related markers (p-eIF2 alpha, IRE1 alpha, CHOP, GRP78) were decreased after treatment of EDA compared to HDM group. Malondialdehyde (MDA), glutathione (GSH), hydrogen peroxide (H2O2), and superoxide dismutase (SOD) were detected to evaluate the oxidant stress in lung tissues. EDA showed a protective effect against oxidant stress. In conclusion, our findings demonstrated that EDA could suppress allergic airway inflammation by inhibiting oxidative stress and ERS, suggesting to serve as an adjunct medication for asthma in the future.

Background Allergic asthma has been regarded as an inflammatory disease mediated by type 2 immunity. The treatment of progressive forms of asthma remains unsatisfactory despite substantial progress in drug development. Lentinan (LTN), a specific polysaccharide derived from Lentinus edodes, exhibits anti-inflammatory and immunomodulatory functions. Nevertheless, the effect and underlying mechanisms of Lentinan on asthma remain unclear. Purpose This research investigated the regulatory role of Lentinan on allergic airway inflammation and epithelial barrier dysfunction in HDM (house dust mite)-induced asthma. Study design HDM-induced C57BL/6 mice received different dosages of Lentinan through intraperitoneal injections, to observe the effect of Lentinan against allergic airway inflammation and epithelial barrier dysfunction in asthma. Methods Mice were intranasally administered HDM extract solution on days 0, 1, 2 and on days 8 to 12, establishing the allergic asthma model. On days 8 to 12, mice were intraperitoneally administered varying doses of Lentinan (5/10/20mg/kg) 1h before HDM challenge. On day 14, samples were harvested for analysis. Cell counting, flow cytometry, ELISA, HE and PAS staining, IF staining, western blotting, RT-PCR, and bioinformatic analysis were conducted to delve into the underlying functions and mechanisms of Lentinan in asthma. Results Our study revealed that the treatment of Lentinan significantly ameliorated allergic airway inflammation and improved epithelial barrier dysfunction in experimental mice. Following Lentinan treatment, there was a significant reduction in eosinophil counts, accompanied by a diminished presence of type 2 cytokines. Reversal of epithelial barrier dysfunction after treatment was also observed. The therapeutic mechanism involved suppression of the PI3K/AKT/ NF-κB pathway. Conclusion Our research illuminated the protective role of Lentinan in allergic airway inflammation and impaired epithelial barrier, suggesting LTN could be an innovative and promising candidate for asthma treatment.

Our previous study demonstrated that acupuncture with low frequency electrical stimulation (Acu-LFES) attenuates skeletal muscle atrophy by improving muscle progenitor cell regeneration. The present study examines whether Acu-LFES improves revascularization, innervation, and protein anabolism in muscle of chronic kidney disease (CKD) mice. CKD was induced by the 5/6 nephrectomy in mice. Acu-LFES treatment was applied in hindlimbs of CKD mice. Pro-teins from hindlimb (gastrocnemius), forelimb (triceps brachii) and back (longissimus) muscles were isolated and Pro-tein synthesis was measured by the surface-sensing of translation (SUnSET) assay. Exosomes were isolated using serial centrifugation and concentration and size of the collected exosomes were measured using a NanoSight instrument. The mature microRNA library was validated using a High Sensitivity DNA chip. Protein synthesis was enhanced in the Acu/LFES-treated gastrocnemius; however, in non-Acu/LFES treated muscles, triceps brachii and longissimus, protein synthesis was also significantly increased. These increases were accompanied with increased myogenesis markers myoD and myogenin. The mRNA expression of PDGF and ENO2 were enhanced by Acu/LFES. The protein amount of Igf-1, Igf-1 receptor, VEGF (a protein that stimulates the formation of blood vessels), and peripherin (expressed mainly in the nervous system) were also increased by Acu/LFES. Deep sequencing revealed that miR-5107-5p and miR-30-5p were sharply decreased in serum exosomes of Acu/LFES mice. Using a luciferase reporter assay, we demonstrated that miR-5107-5p directly inhibits VEGF, and miR-30-5p inhibits ENO2. Conclusions: Acu-LFES treatment increases myogenesis, angiogenesis and neurogenesis, as well as protein synthesis. Acu/LFES inhibits miR-5107 and miR-30, resulting in increased VEGF and ENO2 contributing to these processes.