ABSTRACT
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.
ABSTRACT
OBJECTIVE: To investigate the potential therapeutic role of porous SiO2 -coated ultrasmall selenium particles nanospheres (Se@SiO2 nanospheres) pretreatment in acute pancreatitis (AP) and to investigate the related mechanism. METHODS: C57BL/6 mice were randomized to the normal control (CON) group, the AP (induced by cerulein injection) (CAE) group, and AP pretreated with Se@SiO2 nanocomposites at 1 and 2 mg/kg (CAE + 1 or 2 mg/kg Se@SiO2 ) groups, respectively. Serum levels of amylase and lipase, inflammatory cytokines (interleukin [IL]-6, IL-1ß and tumor necrosis factor [TNF]-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were measured, and histopathology was performed to examine the tissue samples of the pancreas, lungs, kidneys and liver. Immunofluorescence assay of reactive oxygen species (ROS), myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were conducted, and levels of MPO, malondialdehyde, superoxide dismutase and glutathione were evaluated. Finally, Western blot analysis was used to evaluate protein expressions of Nrf2, HO-1, NQO1, TLR4, MyD88 and p-p65 in pancreatic tissue. RESULTS: Se@SiO2 nanospheres alleviated pathological damage to the pancreas, and reduced pancreatic enzymes and inflammatory cytokines. Injury to other organs such as the liver, lungs and kidneys was also alleviated, as indicated by decreased ALT, AST, BUN, and Cr levels as well as improved histopathology. Moreover, Se@SiO2 nanospheres reduced oxidative stress, and ultimately inhibited TLR4/ MyD88/p-p65 pathway and increased the protein expressions of NQO1, Nrf2, and HO-1. CONCLUSION: Se@SiO2 nanospheres may alleviate AP by relieving oxidative stress and targeting the TLR4/Myd88/p-p65 and NQO1/Nrf2/HO-1 pathways.
Subject(s)
Ceruletide , Nanospheres , Pancreatitis , Selenium , Acute Disease , Animals , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Oxidative Stress , PorosityABSTRACT
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.
