ABSTRACT
Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra-conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory-polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein-based conduits. Moreover, the NGC can gradually regulate the intra-conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.
Subject(s)
Fibroins , Nerve Regeneration , Peripheral Nerve Injuries , Animals , Nerve Regeneration/drug effects , Nerve Regeneration/physiology , Rats , Peripheral Nerve Injuries/therapy , Fibroins/chemistry , Fibroins/pharmacology , Disease Models, Animal , Rats, Sprague-Dawley , Schwann Cells/metabolism , Guided Tissue Regeneration/methods , Inflammation , Tissue Scaffolds/chemistry , Sciatic Nerve/injuriesABSTRACT
BACKGROUND: Osteoclasts are the major players in bone resorption and have always been studied in the prevention and treatment of osteoporosis. Previous studies have confirmed that a variety of flavonoids inhibit osteoporosis and improve bone health mainly through inhibiting osteoclastogenesis. Oroxin B (OB) is a flavonoid compound extracted from traditional Chinese herbal medicine Oroxylum indicum (L.) Vent, exerts potent antitumor and anti-inflammation effect, but its effect on osteoclastogensis remains unknown. METHODS: We comprehensively evaluated the effect of OB on the formation and function of osteoclasts and the underling mechanism by bone marrow-derived macrophage in vitro. In vivo, we used mice ovariectomized model to verify the protective effect of OB. RESULTS: OB was found to inhibit osteoclast formation and bone resorption function in vitro, in a dose-dependent manner and the increased osteoclastic-related genes induced by RANKL (NFATc1, c-fos, cathepsin K, RANK, MMP9 and TRAP) were also attenuated following OB treatment. Mechanistical investigation showed OB abrogated the increased phosphorylation level of MAPK and NF-κB pathway, and diminished the expression of the vital transcription factors for osteoclastogenesis. OB also prevented ovariectomy (OVX)-induced bone loss by inhibiting osteoclast formation and activity in mice. CONCLUSION: Our study demonstrated that OB may act as an anti-osteoporosis agent by inhibiting osteoclast maturation and attenuating bone resorption.
Subject(s)
Bone Resorption/drug therapy , Disaccharides/pharmacology , Flavones/pharmacology , Osteoclasts/drug effects , Ovariectomy , Animals , Cells, Cultured , Male , Mice , Mice, Inbred C57BL , Osteoclasts/metabolism , Osteogenesis/drug effectsABSTRACT
OBJECTIVE: To explore the effect of Jiawei Yupingfeng Powder (JYP) on T-lymphocyte subsets in patients with senile chronic bronchitis in acute onset stage (SCB-AOS). METHODS: Patients were divided, according to the randomized controlled principle, into two groups, the 44 patients in the treated group and the 40 in the control group. The conventional western medicinal therapy was given to both groups, but to the treated group, JYP was administered additionally. The therapeutic course to them was 14 days. Changes of CD3, CD4, CD8 and the ratio of them were observed. RESULTS: Increase of CD3, CD4 and CD4/CD8 (P < 0.05) and decrease of CD8 (P < 0.01) were significantly shown in the treated group after treatment, but no change in the control group. Besides, comparison of the total effective rate in the two groups also showed significant difference (P < 0.05). CONCLUSION: Cellular immune function disturbance exists in patients with SCB-AOS, JYP could enhance the efficacy by way of modulating cellular immune function.