Combining Porous Se@SiO2 Nanocomposites and dECM Enhances the Myogenic Differentiation of Adipose-Derived Stem Cells.

Background: Volumetric Muscle Loss (VML) denotes the traumatic loss of skeletal muscle, a condition that can result in chronic functional impairment and even disability. While the body can naturally repair injured skeletal muscle within a limited scope, patients experiencing local and severe muscle loss due to VML surpass the compensatory capacity of the muscle itself. Currently, clinical treatments for VML are constrained and demonstrate minimal efficacy. Selenium, a recognized antioxidant, plays a crucial role in regulating cell differentiation, anti-inflammatory responses, and various other physiological functions. Methods: We engineered a porous Se@SiO2 nanocomposite (SeNPs) with the purpose of releasing selenium continuously and gradually. This nanocomposite was subsequently combined with a decellularized extracellular matrix (dECM) to explore their collaborative protective and stimulatory effects on the myogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs). The influence of dECM and NPs on the myogenic level, reactive oxygen species (ROS) production, and mitochondrial respiratory chain (MRC) activity of ADSCs was evaluated using Western Blot, ELISA, and Immunofluorescence assay. Results: Our findings demonstrate that the concurrent application of SeNPs and dECM effectively mitigates the apoptosis and intracellular ROS levels in ADSCs. Furthermore, the combination of dECM with SeNPs significantly upregulated the expression of key myogenic markers, including MYOD, MYOG, Desmin, and myosin heavy chain in ADSCs. Notably, this combination also led to an increase in both the number of mitochondria and the respiratory chain activity in ADSCs. Conclusion: The concurrent application of SeNPs and dECM effectively diminishes ROS production, boosts mitochondrial function, and stimulates the myogenic differentiation of ADSCs. This study lays the groundwork for future treatments of VML utilizing the combination of SeNPs and dECM.

Molecular targets and mechanisms involved in the action of Banxia Shumi decoction in insomnia treatment.

Insomnia is a common sleep-wake rhythm disorder, which is closely associated with the occurrence of many serious diseases. Recent researches suggest that circadian rhythms play an important role in regulating sleep duration and sleep quality. Banxia Shumi decoction (BSXM) is a well-known Chinese formula used to treat insomnia in China. However, the overall molecular mechanism behind this therapeutic effect has not yet been fully elucidated. This study aimed to identify the molecular targets and mechanisms involved in the action of BSXM during the treatment of insomnia. Using network pharmacology and molecular docking methods, we investigated the molecular targets and underlying mechanisms of action of BSXM in insomnia therapy. We identified 8 active compounds from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the traditional Chinese medicine integrative database that corresponded to 26 target genes involved in insomnia treatment. The compound-differentially expressed genes of the BXSM network indicated that cavidine and gondoic acid could potentially become key components of drugs used for insomnia treatment. Further analysis revealed that GSK3B, MAPK14, IGF1R, CCL5, and BCL2L11 were core targets significantly associated with the circadian clock. Pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes revealed that epidermal growth factor receptor tyrosine kinase inhibitor resistance was the most prominently enriched pathway for BSXM in the insomnia treatment. The forkhead box O signaling pathway was also found to be significantly enriched. These targets were validated using the Gene Expression Omnibus dataset. Molecular docking studies were performed to confirm the binding of cavidine and gondoic acid to the identified core targets. To our knowledge, our study confirmed for the first time that the multi-component, multi-target, and multi-pathway characteristics of BXSM may be the potential mechanism for treating insomnia with respect to the circadian clock gene. The results of this study provided theoretical guidance for researchers to further explore its mechanism of action.

Porous Se@SiO2 nanoparticles improve oxidative injury to promote muscle regeneration via modulating mitochondria.

Background: Acute skeletal muscle injuries are common among physical or sports traumas. The excessive oxidative stress at the site of injury impairs muscle regeneration. The authors have recently developed porous Se@SiO2 nanoparticles (NPs) with antioxidant properties. Methods: The protective effects were evaluated by cell proliferation, myogenic differentiation and mitochondrial activity. Then, the therapeutic effect was investigated in a cardiotoxin-induced muscle injury rat model. Results: Porous Se@SiO2 NPs significantly protected the morphological and functional stability of mitochondria, thus protecting satellite cells from H2O2-induced damage to cell proliferation and myogenic differentiation. In the rat model, intervention with porous Se@SiO2 NPs promoted muscle regeneration. Conclusion: This study reveals the application potential of porous Se@SiO2 NPs in skeletal muscle diseases related to mitochondrial dysfunction.

Muscle injuries are very common in daily life and in sports. When a muscle is injured, the local response inhibits the regeneration and differentiation of stem cells inside the muscle, thus hindering muscle regeneration. The authors have recently developed a nanoparticle with the ability to protect muscle stem cell function, promote stem cell proliferation and differentiation and facilitate muscle regeneration after skeletal muscle injury in rats. Thus, this study reveals the potential of porous Se@SiO₂ nanoparticles in skeletal muscle diseases associated with mitochondrial dysfunction.

Porous Se@SiO2 Nanoparticles Enhance Wound Healing by ROS-PI3K/Akt Pathway in Dermal Fibroblasts and Reduce Scar Formation.

Hypertrophic scarring, which is characterized by excessive extracellular matrix deposition and abnormal fibroblast homeostasis, is an undesirable outcome of dermal wound healing. Once formed, the scar will replace the normal function of local skin, and there are few noninvasive clinical treatments that can cure it. Se@SiO2 nanoparticles were synthesized to suppress oxidative stress, which induced the presence and activation of myofibroblasts during wound recovery. The characterization, antioxidant capacity and biological safety of Se@SiO2 NPs were evaluated. A full-thickness excisional wound model was established, and the wounds were divided into three groups. The re-epithelization and distribution of collagen fibers were assessed using hematoxylin and eosin staining and Masson's trichome staining after specific treatments. Our results revealed that the Se@SiO2 NPs accelerated dermal wound healing and suppressed the formation of hypertrophic scars, accompanied by oxidative stress inhibition. Moreover, we found that Se@SiO2 NPs worked by activating the PI3K/Akt pathway and upregulating the phosphorylation of Akt. The findings of our study provide a new method to promote dermal scar-free wound healing by suppressing excessive oxidative stress and through PI3K/Akt pathway activation.

[Effect of Banxia Xiexin Decoction on intestinal flora of mice with ulcerative colitis induced by dextran sodium sulfate].

The aim of this paper was to investigate the effect of Banxia Xiexin Decoction(BXD) on inflammatory factors and intestinal flora in a dextran sulfate sodium induced ulcerative colitis(DSS-UC) mouse model, and to explore the mechanism of BXD in treating ulcerative colitis from the perspective of flora disorder. Forty C57 BL/6 J mice were randomly divided into control group, model group and BXD group. A 2.5% DSS-induced ulcerative colitis model was established. On the 8 th day, normal saline, normal saline, and BXD were given daily for 14 days. After 14 days, HE staining was used to observe histopathological changes of the colon. Serum inflammatory factor content was detected by ELISA, and the change of intestinal flora in mice feces was detected by 16 S rRNA sequencing technology. Compared with control group, the colonic tissue of mice in model group was damaged seriously, and the contents of IL-6 and TNF-α in serum were significantly increased(P<0.05). Compared with model group, mice in BXD group had less colonic damage, and the contents of IL-6, TNF-α in serum were decreased significantly(P<0.05). After creation, the richness of Patescibacteria was increased significantly at the phylum level(P<0.05). At the same time, the richness of Faecalibaculum(P<0.01), norank_f_Muribaculaceae(P<0.01) were decreased significantly at the genus level, while the richness of Turicibacter(P<0.01), Romboutsia(P<0.01), Clostridium_sensu_stricto_1(P<0.01) were increased significantly. After the intervention with BXD, the content of Patescibacteria was significantly reduced at the phylum level(P<0.05), and the contents of Lactobacillus(P<0.01), Clostri-dium_sensu_stricto_1(P<0.01), Enterorhabdus(P<0.01), Candidatus_Saccharimonas(P<0.05), Eubacterium_fissicatena_group(P<0.05) were decreased significantly at the genus level, while the contents of Dubosiella, Bacteroides and Allobaculum were increased significantly. Therefore, BXD could significantly improve the symptoms of DSS-UC mice. It not only could reduce the contents of IL-6 and TNF-α, but also could reduce the richness of Patescibacteria at the phylum level, and those of Clostridium_sensu_stricto_1, Candidatus_Saccharimonas, Eubacterium_fissicatena_group at the genus level. Inaddition, BXD could increase the richness of Bacteroides and Bifidobacterium. It suggested that BXD could play a role in the treatment of ulcerative colitis partially through reducing inflammatory factors and regulating the structure of the gut microbiota.

Urine metabolomics of rats with chronic atrophic gastritis.

BACKGROUND/AIM: To use liquid chromatography-mass spectrometry (LC-MS) to identify endogenous differential metabolites in the urine of rats with chronic atrophic gastritis (CAG). MATERIALS AND METHODS: Methylnitronitrosoguanidine (MNNG) was used to produce a CAG model in Wistar rats, and HE staining was used to determine the pathological model. LC-MS was used to detect the differential metabolic profiles in rat urine. Diversified analysis was performed by the statistical method. RESULTS: Compared with the control group, the model group had 68 differential metabolites, 25 that were upregulated and 43 that were downregulated. The main metabolic pathways were D-glutamine and D-glutamic acid metabolism, histidine metabolism and purine metabolism. CONCLUSION: By searching for differential metabolites and metabolic pathways in the urine of CAG rats, this study provides effective experimental data for the pathogenesis and clinical diagnosis of CAG.

Porous Se@SiO2 nanosphere-coated catheter accelerates prostatic urethra wound healing by modulating macrophage polarization through reactive oxygen species-NF-κB pathway inhibition.

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.