A peptide named SEM18, possessing structural similarity to the binding site of tumor necrosis factor (TNF)-α to TNF receptor 1 (TNFR1), was designed. We investigated whether the SEM18 peptide can mitigate lipopolysaccharide (LPS)-induced liver injury in mice. Adult male Balb/cJ mice received LPS (15 mg/kg; LPS group) or LPS plus SEM18 (LSEM group). Control groups were run simultaneously. At 2 h after LPS, the first dose of SEM18 (0.3 mg/kg) was administered, followed by three supplemental doses of SEM18 (0.15 mg/kg, every 2 h). At 24 h after LPS, surviving mice were euthanized for analyses. Compared with the LPS group, binding of TNF-α to TNFR1 in liver tissues was significantly lower in the LSEM group (p < 0.001). Plasma concentrations of aspartate transaminase and alanine transaminase, as well as Suzuki’s scores (liver damage assessment), wet/dry weight ratios, levels of polymorphonuclear neutrophil infiltration, and levels of mitochondrial injury in liver tissues, of the LSEM group were significantly lower than in the LPS group (all p < 0.05). Levels of necroptosis, pyroptosis, apoptosis, and autophagy upregulation in liver tissues in the LSEM group were also significantly lower than in the LPS group (all p < 0.05). Notably, exogenous TNF-α counteracted these effects of SEM18. SEM18 peptide mitigates LPS-induced liver injury in mice.

This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all p < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all p < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.

Background/Objectives: Psoriasis is a chronic systemic inflammatory disease. Evidence on the efficacy of different mesenchymal stem cell (MSC) exosomes for psoriasis remains limited. This study aimed to evaluate the therapeutic effects of different MSC exosomes in mitigating psoriasis. Methods: The efficacy of human placenta MSC (hPMSC) and human umbilical cord MSC (hUCMSC) exosomes was compared in an imiquimod (IMQ)-induced psoriasis murine model. A meta-analysis was performed to incorporate the results of studies using IMQ-induced psoriasis murine models to compare MSC exosome treatments (exosome group) with vehicle or no-treatment controls (control group). Results: In this murine study, both the hPMSC and hUCMSC exosomes showed better effectiveness in reducing epidermal thickness and skin tissue cytokines than controls, but no significant difference was observed between the two MSC exosomes. Seven studies were included in the meta-analysis. Clinical severity scores were significantly lower in the exosome group than in the controls (standardized mean difference [SMD]: −1.886; 95% confidence interval [CI]: −3.047 to −0.724). Epidermal thickness was significantly reduced (SMD: −3.258; 95% CI: −4.987 to −1.529). No significant differences were found in most skin cytokines between the groups, although tumor necrosis factor-α mRNA (SMD: −0.880; 95% CI: −1.623 to −0.136) and interleukin-17A protein levels (SMD: −2.390; 95% CI: −4.522 to −0.258) were both lower in the exosome group. Meta-regression revealed a greater improvement in clinical scores in studies using hUCMSC exosomes compared to other MSC sources (p = 0.030). Conclusions: hUCMSC exosomes have been studied more extensively than other MSC exosomes. MSC exosomes reduce clinical severity and epidermal hyperplasia.

Background: Aspiration pneumonia (AP), which can be caused by gastric content inhalation into the lower airways, causes acute lung injury (ALI) through complex mechanisms, including inflammation, oxidative stress, and apoptosis. Here, we evaluated the efficacy of exosomes derived from human placental mesenchymal stem cells (hpMSCs) in mitigating ALI in a murine model of AP. We also investigated the role of hsa-let-7i-5p, the most abundant miRNA in hpMSC-derived exosomes, in this respect.Methods: Adult male C57BL/6 mouse AP models were administered hpMSC-derived exosomes (APExo group) or phosphate-buffered saline (AP group) intra-tracheally. After 48 h, the mice were euthanized and evaluated. The effects of hsa-let-7i-5p were assessed by specific inhibition or overexpression.Results: Compared with the APExo group, the AP group exhibited significantly greater ALI, as evidenced by histological damage, increased lung injury scores, impaired lung function, increased leukocyte infiltration, and elevated tissue edema (all P < 0.05). The untreated AP group also showed more inflammation, characterized by nuclear factor-κB upregulation, macrophage M1 polarization, and cytokine level elevation (tumor necrosis factor-α, interleukin-1β, and interleukin-6), as well as increased oxidation and activation of the apoptosis pathway (all P < 0.05). Notably, the therapeutic effects of hpMSC-derived exosomes were compromised by specific inhibition of hsa-let-7i-5p. Furthermore, engineered exosomes derived from genetically modified RAW264.7 overexpressing hsa-let-7i-5p demonstrated therapeutic effects against AP similar to those obtained with hpMSC-derived exosomes.Conclusions: In a murine AP model, intra-tracheal administration of hpMSC-derived exosomes has ALI-mitigating effects, involving inflammation, oxidation, and apoptosis modulation, with hsa-let-7i-5p playing a pivotal mediating role.

Testicular torsion–detorsion (T/D) induces ischemia–reperfusion injury, leading to mitochondrial dysfunction, oxidative stress, apoptosis, and spermatogenic impairment. Pyrroloquinoline quinone (PQQ), a redox cofactor with mitochondrial-protective, antioxidant, and anti-apoptotic properties, was evaluated for its therapeutic potential in a rat T/D model. Young adult male Sprague-Dawley rats underwent 720° spermatic cord rotation for 2 h followed by detorsion and were assigned to T/D or T/D + PQQ groups, with sham-operated controls run in parallel. PQQ (400 mg/kg body weight) was administered orally once daily for 4 weeks. T/D resulted in severe disruption of testicular architecture, disorganization of seminiferous epithelium, reduced sperm count and testis-to-body weight ratio, increased hypoxia-inducible factor-1α and malondialdehyde, decreased superoxide dismutase 2, impaired oxidative phosphorylation (OXPHOS), and enhanced apoptosis. Notably, PQQ treatment significantly preserved testicular structure, improved sperm counts, reduced oxidative stress, restored OXPHOS, and suppressed apoptosis (all p < 0.05. T/D + PQQ vs. T/D). These findings indicate that PQQ protects against T/D-induced testicular injury. The underlying mechanisms may involve the attenuation of oxidative stress, the preservation of mitochondrial function, and the limitation of apoptosis, supporting its potential as a therapeutic strategy for testicular IRI.