Fabrication of a Polylactide-Glycolide/Poly-ε-Caprolactone/Dextran/Plastrum Testudinis Extract Composite Anti-Inflammation Nanofiber Membrane via Electrospinning for Annulus Fibrosus Regeneration.

Tissue engineering is a promising approach for the treatment of chronic lower back pain (LBP) caused by intervertebral disc degeneration (IDD) resulting from degeneration and inflammation of annulus fibrosus (AF) tissue. However, scaffold with an anti-inflammatory effect on AF cells has not been reported. In this study, we fabricated a polylactide-glycolide (PLGA)/poly-ε-caprolactone (PCL)Zdextran (DEX) composite membrane loaded with plastrum testudinis extract (PTE), a Traditional Chinese Medicine herbal extract, via electrospinning. The membranes were characterized by mechanical measurements and scanning electron microscopy (SEM). Using an in vitro inflammation model induced by interleukin (IL)-1ß, the cytocompatibility and anti-inflammatory effects of the composites were investigated by CCK-8 assay and flow cytometry. Potential regulatory mechanisms were examined by RT-qPCR and Western blotting. The results showed that the P10P8D2 (PLGA 10 g, PCL 8 g, DEX 2 g) composite nanofiber membrane exhibited the most uniform diameter distribution, best mechanical properties, a moderate degradation rate, and the best cytocompatibility characteristics. The optimal concentration of PTE was 120 µg/mL. Importantly, P10P8D2 combined with PTE exhibited anti-inflammatory and cell proliferation promotion effects. Moreover, the NF-κBB/NLRP3/IL-ß signaling pathway was inactivated. Our findings suggested that the nanofiber membrane composed of P10P8D2 and PTE has anti-inflammatory and pro-proliferation effects on AF cells. It may provide an effective strategy for AF tissue regeneration.

Cationic Polymer Brush-Modified Carbon Nanotube-Meditated eRNA LINC02569 Silencing Attenuates Nucleus Pulposus Degeneration by Blocking NF-κB Signaling Pathway and Alleviate Cell Senescence.

Enhancer RNAs (eRNAs) are noncoding RNAs that synthesized at active enhancers. eRNAs have important regulatory characteristics and appear to be significant for maintenance of cell identity and information processing. Series of functional eRNAs have been identified as potential therapeutic targets for multiple diseases. Nevertheless, the role of eRNAs on intervertebral disc degeneration (IDD) is still unknown yet. Herein, we utilized the nucleus pulposus samples of patients and identified a key eRNA (LINC02569) with the Arraystar eRNA Microarray. LINC02569 mostly locates in nucleus and plays an important role in the progress of IDD by activating nuclear factor kappa-B (NF-κB) signaling pathway. We used a cationic polymer brush coated carbon nanotube (oCNT-pb)-based siRNA delivery platform that we previously designed, to transport LINC02569 siRNA (si-02569) to nucleus pulposus cells. The siRNA loaded oCNT-pb accumulated in nucleus pulposus cells with lower toxicity and higher transfection efficiency, compared with the traditional siRNA delivery system. Moreover, the results showed that the delivery of si-02569 significantly alleviated the inflammatory response in the nucleus pulposus cells via inhibiting P65 phosphorylation and preventing its transfer into the nucleus, and meanwhile alleviated cell senescence by decreasing the expression of P21. Altogether, our results highlight that eRNA (LINC02569) plays important role in the progression of IDD and could be a potential therapeutic target for alleviation of IDD.

Panax Notoginseng Saponins Prevent Bone Loss by Promoting Angiogenesis in an Osteoporotic Mouse Model.

With the aging of the population and the extension of life expectancy, osteoporosis is becoming a global epidemic. Although there are several drugs used to treat osteoporosis in clinical practice, such as parathyroid hormone or bisphosphonates, they all have some serious side effects. Therefore, a safer drug is called for osteoporosis, especially for the prevention in the early stage of the disease, not only the treatment in the later stage. Panax notoginseng saponin (PNS), a traditional Chinese herb, has been used as anti-ischemic drug due to its function on improving vascular circulation. In order to verify whether Panax notoginseng saponins (PNS) could be used to prevent osteoporosis, ovariectomy (OVX) was induced in female C57BL/C6J mice, followed by orally administration with 40 mg/kg/d, 80 mg/kg/d, and 160 mg/kg/d of three different dosages of PNS for 9 weeks. Serum biochemical analysis, micro-CT, histological evaluation, and immunostaining of markers of osteogenesis and angiogenesis were performed in the sham, osteoporotic (OVX), and treatment (OVX+PNS) groups. Micro-CT and histological evaluation showed that compared to sham group, the bone mass of OVX group reduced significantly, while it was significantly restored in the moderate-dose PNS (40 mg/kg and 80 mg/kg) treatment groups. The expression of CD31 and osteocalcin (OCN) in the bone tissue of treatment group also increased, suggesting that PNS activated osteogenesis and angiogenesis, which subsequently increased the bone mass. These results confirmed the potential function of PNS on the prevention of osteoporosis. However, in the high dose of PNS (160 mg/kg) group, the antiosteoportic effect had been eliminated, which also suggested the importance of proper dose of PNS for the prevention and treatment of osteoporosis in postmenopausal women.

Electroacupuncture treatment contributes to the downregulation of neuronal nitric oxide synthase and motoneuron death in injured spinal cords following root avulsion of the brachial plexus.

This study was performed in order to investigate the effect of electroacupuncture (EA) on motoneurons and the expression of neuronal nitric oxide synthase (nNOS) following brachial plexus root avulsion (BPRA). A total of 40 female Sprague-Dawley rats underwent BPRA (5th cervical-1st thoracic) and were randomly divided into the avulsion plus EA stimulation (AV+EA) and AV groups. The AV+EA group received a continuous 20-Hz asymmetric bidirectional disperse-dense wave at the acupuncture points (acupoints) of Dazhui (DU4) and Shousanli (LI10) for 15 min on alternate days until the animals were sacrificed, at 1, 2, 3 and 6 weeks. The AV group received no treatment. The cryostat sections of the 7th cervical segments were prepared and stained with neuronal nitric oxide synthase nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and histochemically stained and counterstained with neutral red (NR). The number of nNOS-positive motoneurons on the lesion side and survived motoneurons on both sides of the 7th cervical segments were blindly counted and compared between the two groups. The results demonstrated that the number of nNOS-positive motoneurons was significantly lower in the AV+EA group compared with that in the AV group and the percentage of survived motoneurons was significantly higher compared with that of the AV group at 2 and 3 weeks. However, the number of nNOS-positive motoneurons and the percentage of survived motoneurons were not significantly different between the two groups at 1 and 6 weeks. These results indicated that, during the early period after BPRA, EA stimulation at the acupoints of Dazhui (DU4) and Shousanli (LI10) may significantly reduce the number of nNOS-positive motoneurons and protect against motoneuron death.