A targeted antibody-based array reveals a serum protein signature as biomarker for adolescent idiopathic scoliosis patients.

BACKGROUND: Evident adolescent idiopathic scoliosis (AIS) incurs high treatment costs, low quality of life, and many complications. Early screening of AIS is essential to avoid progressing to an evident stage. However, there is no valid serum biomarker for AIS for early screening. METHODS: Antibody-based array is a large-scale study of proteins, which is expected to reveal a serum protein signature as biomarker for AIS. There are two segments of the research, including biomarkers screening and validation. In the biomarkers screening group, a total of 16 volunteers participated in this study, and we carried out differentially expressed proteins screening via protein array assay between No-AIS group and the AIS group, through which GeneSet enrichment analysis was performed. In the validation group with a total of 62 volunteers, the differentially expressed proteins from screening group were verified by Enzyme-Linked immunosorbent assay (ELISA), and then multiple regression analysis. RESULTS: In our study, there were twenty-nine differentially expressed proteins in AIS, through Protein array assay and GeneSet enrichment analysis in the biomarkers screening group. Then the expression of FAP, CD23 and B2M decreased as the degree of AIS increased via ELISA in validation group (FAP, p < 0.0001; CD23, p = 0.0002; B2M, p < 0.0001). Further, the results of multiple regression analysis showed that FAP, CD23 are linked to Cobb angle, whereas B2M were excluded because of multicollinearity. CONCLUSIONS: Altogether, we found that serum protein FAP and CD23 are intimately related to AIS, suggesting FAP and CD23 are expected to serve as the serum biomarkers, which significantly facilitate frequent longitudinal monitoring as to keep track of disease progression and tailor treatment accordingly.

Bexarotene improves motor function after spinal cord injury in mice.

Spinal cord injury is a challenge in orthopedics because it causes irreversible damage to the central nervous system. Therefore, early treatment to prevent lesion expansion is crucial for the management of patients with spinal cord injury. Bexarotene, a type of retinoid, exerts therapeutic effects on patients with cutaneous T-cell lymphoma and Parkinson's disease. Bexarotene has been proven to promote autophagy, but it has not been used in the treatment of spinal cord injury. To investigate the effects of bexarotene on spinal cord injury, we established a mouse model of T11-T12 spinal cord contusion and performed daily intraperitoneal injection of bexarotene for 5 consecutive days. We found that bexarotene effectively reduced the deposition of collagen and the number of pathological neurons in the injured spinal cord, increased the number of synapses of nerve cells, reduced oxidative stress, inhibited pyroptosis, promoted the recovery of motor function, and reduced death. Inhibition of autophagy with 3-methyladenine reversed the effects of bexarotene on spinal cord injury. Bexarotene enhanced the nuclear translocation of transcription factor E3, which further activated AMP-activated protein kinase-S-phase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signaling pathways. Intravenous injection of transcription factor E3 shRNA or intraperitoneal injection of compound C, an AMP-activated protein kinase blocker, inhibited the effects of bexarotene. These findings suggest that bexarotene regulates nuclear translocation of transcription factor E3 through the AMP-activated protein kinase-S-phase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signal pathways, promotes autophagy, decreases reactive oxygen species level, inhibits pyroptosis, and improves motor function after spinal cord injury.

Safranal inhibits estrogen-deficiency osteoporosis by targeting Sirt1 to interfere with NF-κB acetylation.

BACKGROUND: Osteoporosis is a prevalent bone metabolic disease in menopause, and long-term medication is accompanied by serious side effects. Estrogen deficiency-mediated hyperactivated osteoclasts is the initiating factor for bone loss, which is regulated by nuclear factor-κB (NF-κB) signaling. Safranal (Saf) is a monoterpene aldehyde produced from Saffron (Crocus sativus L.) and possesses multiple biological properties, particularly the anti-inflammatory property. However, Saf's role in osteoporosis remains unknown. PURPOSE: This study aims to validate the role of Saf in osteoporosis and explore the potential mechanism. STUDY DESIGN: The RANKL-exposed mouse BMM (bone marrow monocytes) and the castration-mediated osteoporosis model were applied to explore the effect and mechanism of Saf in vitro and in vivo. METHOD: The effect of Saf on osteoclast formation and function were assessed by TRAcP staining, bone-resorptive experiment, qPCR, immunoblotting and immunofluorescence, etc. Micro-CT, HE, TRAcP and immunohistochemical staining were performed to estimate the effects of Saf administration on OVX-mediated osteoporosis in mice at imaging and histological levels. RESULTS: Saf concentration-dependently inhibited RANKL-mediated osteoclast differentiation without affecting cellular viability. Meanwhile, Saf-mediated anti-osteolytic capacity and Sirt1 upregulation were also found in ovariectomized mice. Mechanistically, Saf interfered with NF-κB signaling by activating Sirt1 to increase p65 deacetylation and inactivating IKK to decrease IκBα degradation. CONCLUSION: Our results support the potential application of Saf as a therapeutic agent for osteoporosis.

Chrysophanol prevents IL-1ß-Induced inflammation and ECM degradation in osteoarthritis via the Sirt6/NF-κB and Nrf2/NF-κB axis.

Osteoarthritis (OA) is a common joint illness that negatively impacts people's lives. The main active ingredient of cassia seed or rhubarb is chrysophanol. It has various pharmacological effects including anticancer, anti-diabetes and blood lipid regulation. Previous evidence suggests that chrysophanol has anti-inflammatory properties in various diseases, but its effect on OA has not been investigated yet. In this study, chrysophanol inhibited IL-1ß -induced expression of ADAMTS-4, MMP13, COX-2 and iNOS. Meanwhile, it can inhibit aggrecan and collagen degradation in osteoarthritic chondrocytes induced by IL-1ß.Further studies depicted that SIRT6 silencing eliminated the chrysophanol effect on IL-1ß. The results demonstrated that chrysophanol could stimulate SIRT6 activation and, more importantly, increase SIRT6 levels. We also discovered that chrysophanol might impede the NF-κB pathway of OA mice's chondrocytes induced by IL-1ß, which could be because it depends on SIRT6 activation to some extent. It had also been previously covered that chrysophanol could produce a marked effect on Nrf2/NF-κB axis [1]. Therefore, we can infer that chrysophanol may benefit chondrocytes by regulating the SIRT6/NF-κB and Nrf2/NF-κB signaling axis.We examined the anti-inflammatory mechanism and the impact of chrysophanol on mice in vitro and in vivo. In summary, we declare that chrysophanol diminishes the inflammatory reaction of OA in mice in vitro by regulating SIRT6/NF-κB and Nrf2/NF-κB signaling pathway and protects articular cartilage from degradation in vivo. We can infer that chrysophanol could be an efficient therapy for OA.

Gamma-oryzanol alleviates intervertebral disc degeneration development by intercepting the IL-1ß/NLRP3 inflammasome positive cycle.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1ß/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown. PURPOSE: This study aims to validate the role of Ory in IVDD and explore the potential mechanism. STUDY DESIGN: Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory. METHOD: The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1ß-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels. RESULTS: Ory treatment inhibited IL-1ß-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1ß/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development. CONCLUSION: Our results support the potential application of Ory as a therapeutic compound for IVDD.

Engineering the surfaces of orthopedic implants with osteogenesis and antioxidants to enhance bone formation in vitro and in vivo.

Limited osteointegration of orthopedic implants with surrounding tissues has been the leading issue until the failure of orthopedic implants in the long term, which could be induced by multiple factors, including infection, limited abilities for bone formation and remodeling, and an overstressed reactive oxygen species (ROS) environment around implants. To address this challenge, a multifunctional coating composed of tannic acid (TA), nanohydroxyapatite (nHA) and gelatin (Gel) was fabricated by a layer-by-layer (LBL) technique, into which TA, nHA, and Gel were integrated, and their respective functions were utilized to synergistically promote osteogenesis. The fabrication process of (TA@nHA/Gel)n coatings and related bio-multifunctionalities were thoroughly investigated by various techniques. We found that the (TA@nHA/Gel)n coatings showed strong antioxidant activity and accelerated cellular attachment in the early stage and proliferation in the long term, largely enhancing osteogenesis in vitro and promoting bone formation in vivo. We believe our findings will guide the design of orthopedic implants in the future, and the strategy developed here could pave the way for multifunctional orthopedic implant coating and protein-related coatings with various potential applications, including biosensors, catalysis, tissue engineering, and life science.

Nerve growth factor (NGF) with hypoxia response elements loaded by adeno-associated virus (AAV) combined with neural stem cells improve the spinal cord injury recovery.

The ischemia and hypoxia microenvironment after spinal cord injury (SCI) makes SCI repair a challenging problem. With various stimulus, chances for neural stem cells (NSCs) to differentiate into neurons, astrocytes, oligodendrocytes are great and is considered as a potential source of the stem cell therapy to SCI. Our research used adeno-associated virus (AAV) to carry the target gene to transfect neural stem cells. Transfected NSCs can express nerve growth factor (NGF) navigated by five hypoxia-responsive elements (5HRE). Therefore, the 5HRE-NGF-NSCs could express NGF specifically in hypoxia sites to promote the tissue repair and function recovery. Based on the regeneration of neurocytes and promotion of the recovery found in SCI models, via locomotor assessment, histochemical staining and molecular examinations, our results demonstrated that 5HRE-NGF-NSCs could improve the motor function, neurons survival and molecules expression of SCI rats. Meanwhile, the downregulated expression of autophagy-related proteins indicated the inhibitive effect of 5HRE-NGF-NSCs on autophagy. Our research showed that 5HRE-NGF-NSCs contribute to SCI repair which might via inhibiting autophagy and improving the survival rate of neuronal cells. The new therapy also hampered the hyperplasia of neural glial scars and induced axon regeneration. These positive functions of 5HRE-NGF-NSCs all indicate a promising SCI treatment.

Potential role of microRNAs in the regulation of pyroptosis (Review).

MicroRNAs (miRNAs) perform a variety of important cellular functions, including regulating the cell cycle, apoptosis and differentiation, amongst others. Recent research has demonstrated an essential function performed by miRNAs in regulating pyroptosis, which is a type of programmed cell death associated with inflammatory responses that plays a critical role in numerous diseases. Through direct or indirect action on proteins associated with the pyroptosis signaling pathway, miRNAs are involved in the pathological processes of cardiovascular, kidney and immune diseases, among others. The present review discusses the maturation process of miRNAs and the process of pyroptosis, with a specific focus on the transport of miRNAs to damaged cells via exosomes, shedding vesicles and protein stabilized complexes, as well as the role of different miRNAs in the regulation of pyroptosis through different gene and protein targets. The aim of the present review was to provide a novel insight into the regulatory role of miRNAs in pyroptosis and new treatment options for pyroptosis­associated diseases.

Gelatine nanostructured lipid carrier encapsulated FGF15 inhibits autophagy and improves recovery in spinal cord injury.

Gelatine nanostructured lipid carriers (GNLs) have attracted increasing attention due to their biodegradable status and capacity to capture various biologically active compounds. Many studies demonstrated that fibroblast growth factor therapies after spinal cord injury (SCI) can be used in the future for the recovery of neurons. In this study, the therapeutic effects of GNL-encapsulated fibroblast growth factor 15 (FGF15) and FGF15 were compared in SCI. The FGF15-GNLs had 88.17 ± 1.22% encapsulation efficiency and 4.82 ± 0.12% loading capacity. The effects of FGF15-GNLs and FGF15 were assessed based on the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test and footprint analysis. Immunofluorescent staining was used to identify the expression of autophagy-associated proteins, GFAP (glial fibrillary acidic protein) and neurofilament 200 (NF200). FGF15-GNLs use enhanced the repair after SCI compared to the effect of FGF15. The suppression of autophagy-associated proteins LC3-II and beclin-1, and p62 enhancement by FGF15-GNLs treatment were more pronounced. Thus, the effects of FGF15-GNLs on the recovery after SCI are related to the inhibition of autophagy and glial scar, and promotion of nerve regeneration in SCI.

Grape seed procyanidins suppress the apoptosis and senescence of chondrocytes and ameliorates osteoarthritis via the DPP4-Sirt1 pathway.

Osteoarthritis (OA) is a complicated pathological condition affecting thousands of people around world, many with substantial unmet medical care needs and without any effective therapies. Previous study has indicated that glucagon-like peptide-1 (GLP-1) is involved in the pathological progress of osteoarthritis; however, the role of dipeptidase-4 (DPP4), which regulates the degradation of GLP-1, still remains unclear in osteoarthritis. Herein, after comparing normal mouse cartilage tissues with OA mouse cartilage tissues by histological analysis, we found out that DPP4 was highly expressed in OA cartilage tissues. To investigate the role of DPP4 in osteoarthritis, the apoptosis and senescence of chondrocytes were found to be decreased in vitro when DPP4 was downregulated by siRNA in chondrocytes. Further study showed that the inhibition of DPP4 by procyanidins, a grape seed extract, attenuated apoptosis and senescence of chondrocytes in vitro. Furthermore, the results showed that DPP4 inhibition protects cartilage by activating Sirt1, which has been reported to be associated with many pathophysiological processes, particularly in age-related diseases, such as neurodegenerative disorders and osteoarthritis. In addition, animal experiment results demonstrated that procyanidins were capable of ameliorating the progression of osteoarthritis through the inhibition of DPP4. This study provides a competitive target for the therapeutic treatment of osteoarthritis, and procyanidins were shown to be a potential medicine for the restoration of the effects of osteoarthritis.

Baicalein Attenuates Pyroptosis and Endoplasmic Reticulum Stress Following Spinal Cord Ischemia-Reperfusion Injury via Autophagy Enhancement.

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCIRI) is the main complication after the repair of a complex thoracoabdominal aortic aneurysm. Many clinical treatments are not ideal due to the complex pathophysiological process of this injury. Baicalein (BA), a component derived from the roots of the herb Scutellaria baicalensis, may contribute to the successful treatment of ischemia/reperfusion injury. PURPOSE: In the present study, the effects of BA on spinal cord ischemia-reperfusion injury and the underlying mechanisms were assessed. MATERIALS AND METHODS: Spinal cord ischemia was induced in C57BL/6 mice by blocking the aortic arch. Fifty-five mice were then randomly divided into four groups: Sham, SCIR+Vehicle, SCIR+BA, and SCIR+BA +3MA groups. At 0 and 24 h pre-SCIRI and at 24 h and 7 days post-SCIRI, evaluations with the Basso mouse scale (BMS) were performed. On postoperative 24 h, the spinal cord was harvested to assess pyroptosis, endoplasmic reticulum stress mediated apoptosis and autophagy. RESULTS: BA enhanced the functional recovery of spinal cord ischemia-reperfusion injury. In addition, BA attenuated pyroptosis, alleviated endoplasmic reticulum stress-mediated apoptosis, and activated autophagy. However, the effects of BA on the functional recovery of SCIRI, pyroptosis and endoplasmic reticulum stress-mediated apoptosis were reversed by the inhibition of autophagy. CONCLUSIONS: In general, our findings revealed that BA enhances the functional recovery of spinal cord ischemia-reperfusion injury by dampening pyroptosis and alleviating endoplasmic reticulum stress-mediated apoptosis, which are mediated by the activation of autophagy.

Role of Pyroptosis in Traumatic Brain and Spinal Cord Injuries.

Central nervous system (CNS) trauma, including traumatic brain injury (TBI) and spinal cord injury (SCI), remains a leading cause for morbidity and mortality worldwide. Past research has shown that cell death plays a critical role in the pathophysiology of CNS injuries. More recently, pyroptosis has been identified as a form of programmed inflammatory cell death, and it is a unique form of cell death in various aspects. Mechanistically, pyroptosis can be categorized into canonical (mediated by caspase-1) and non-canonical (mediated by caspase-4/5/11). In canonical pyroptosis, Nod-like receptors (NLRs) inflammasomes play a critical role, and their activation promotes the maturation and secretion of the inflammatory cytokines interleukin-1ß/18 (IL-1ß/18), cleavage of gasdermin D (GSDMD), and ultimately pyroptotic cell death. Despite a plethora of new knowledge regarding pyroptosis, detailed understanding of how pyroptosis is involved in CNS injuries and possible ways to improve clinical outcomes following CNS injuries remain elusive. This review discusses the current knowledge on how pyroptosis is involved in CNS injuries, focusing on new discoveries regarding how pyroptosis activation occurs, differences between CNS cell types following injury, time-course of inflammatory responses, and key regulatory steps of pyroptosis. In addition, we highlight various investigational agents that are capable of regulating key steps in pyroptotic cell death, and we discuss how these agents may be used as therapies to improve outcomes following CNS trauma.

Comparison of the effects of general and local anesthesia in lumbar interlaminar endoscopic surgery.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) with an interlaminar approach is a technique used to treat lumbar disc hernia. It has not yet been established whether general or local anesthesia (LA) is preferable for lumbar interlaminar endoscopic surgery. METHODS: Between October, 2012 and June, 2016, 60 patients were recruited and randomly divided into 2 groups: the general anesthesia (GA) group and the LA group. The patients' basic clinical data, intraoperative patient experience, Oswestry disability index (ODI), visual analog scale (VAS) score, and the postoperative patient satisfaction rate were assessed. RESULTS: Statistically significant differences were found between the two groups in operative time and length of hospital stay. There were no significant differences in postoperative ODI or VAS scores between the two groups during follow-up at 3, 6, and 12 months. One patient in the GA group sustained a nerve root injury intraoperatively. Two patients in the LA group suffered adverse reactions, as did six patients in the GA group. However, 50% of the patients expressed fear about undergoing the surgery with LA, while all patients felt they could undergo the same surgery with GA. CONCLUSIONS: General and LA are both suitable for use in lumbar interlaminar endoscopic surgery. However, GA makes a positive intraoperative surgical experience more likely for the patient.

α-Bisabolol suppresses the inflammatory response and ECM catabolism in advanced glycation end products-treated chondrocytes and attenuates murine osteoarthritis.

As a chronic musculoskeletal degeneration disease, osteoarthritis (OA) clinically manifests as joint pain, stiffness and a limited range of movement. OA has affected the life quality of at least one-tenth of the population but lacks satisfactory treatments. α-Bisabolol (BISA) is a small oily sesquiterpene alcohol widely found in essential oils of chamomile (Matricaria recutita), salvia and wood of Candeia and has multiple biological properties, particularly an anti-inflammatory effect. The purpose of this study is to assess the anti-inflammatory and chondroprotective effect of BISA in OA progression and explore its underlying mechanism. We isolated human chondrocytes and treated them with advanced glycation end products (AGEs) to imitate OA progression in vitro. BISA pretreatment suppressed the AGE-induced inflammatory reaction and extracellular matrix (ECM) degeneration by blocking nuclear factor kappa B (NF-κB), p38 and c-Jun N-terminal kinase (JNK) signaling. Moreover, a mouse destabilization of the medial meniscus (DMM) model was established by surgery to investigate BISA protection in vivo. BISA administration attenuated DMM-induced radiological and histopathological changes relative to the DMM group and resulted in lower OARSI scores. Taken together, the results of our study indicate the potential of BISA in OA therapy.

Anterior decompression through transoral axis slide and rotation osteotomy for salvage of failed posterior occipitocervical fusion: a novel technique note.

Atlantoaxial dislocation could be caused by odontoid fractures or Os odontoideum. The previous surgical techniques in treatment of atlantoaxial dislocation were based on arch remove decompression or anterior atlantoaxial release and atlantoaxial (occipital-cervical) screw fixation-based reduction and fusion. However, for some clinical situations, all of above techniques cannot be applied. In this study, a patient with atlantoaxial dislocation caused by Os odontoideum treated by posterior occipitocervical fusion 20 years ago and failed. We design a novel anterior decompression through transoral axis slide and rotation osteotomy for salvage of this failed posterior occipitocervical fusion case. The C2 body and odontoid process was ventrally slide and rotation at good position after operation as well as the position of plate and screws, the spinal canal was increased significantly after operation too. We suggest this anterior decompression through transoral "C2 slide and rotation" technique is good choice for salvage of failed posterior occipitocervical fusion and some irreducible atlantoaxial dislocation because of the anterior bony fusion, it could direct decompress the spinal cord anteriorly, avoid the odontoid resection, and is feasible and safe technique.

Lysozyme (Lys), Tannic Acid (TA), and Graphene Oxide (GO) Thin Coating for Antibacterial and Enhanced Osteogenesis.

Dental implants have great potential in the global market, around $3.7 billion in 2015, which will increase to $7 billion in 2023 with an annual increase rate of 8.2%. Incorporating antibacterial and osteogenic agents into implants is helpful to make the dental implants successful, which can be endowed by coatings. In recent years, graphene oxide (GO) and its composite materials have shown advances in the biomedical field. Lysozyme (Lys) and tannic acid (TA) are naturally derived, with promising antibacterial and osteogenic properties as well. In the present study, the strong antibacterial and enhanced osteogenic multilayer coating is fabricated using the facile and controllable layer by layer (LBL) technique to integrate GO, Lys, and TA. The thickness of coating exhibited a continuous growth with the deposited process as proved from UV-vis and ellipsometry data, and the physical properties of the coating, such as wettability, roughness, and stiffness are well characterized. The coatings exhibited the synergic effect on the killing bacteria, both Gram-negative bacteria and Gram-positive bacteria represented by E. coli and S. aureus, respectively, and enhancing osteogenesis of dental pulp stem cells (hDPSCs), showing the potential application on coatings of dental implants. Thus, the strategy applied here will inspire the design and development of dual functional surfaces for the success of implanted dental surface in future.

Minimally invasive surgery for degenerative spondylolisthesis: transforaminal or oblique lumbar interbody fusion.

Aim: To compare the outcomes of minimally invasive surgery (MIS) for degenerative spondylolisthesis transforaminal lumbar interbody fusion (TLIF) and oblique lumbar interbody fusion (OLIF). Materials & methods: The clinical and surgical characteristics and outcomes of 38 patients with MIS-OLIF and 55 with MIS-TLIF were retrospectively evaluated. Results: Procedures and hospital stay were shorter and blood loss was less, with MIS-OLIF than with MIS-OLIF. The clinical and radiographic outcomes were similar. Postoperative changes in disk height and foraminal dimension were greater and patient satisfaction was better with MIS-OLIF than with MIS-TLIF. Conclusion: The clinical findings associated with the two procedures were similar; but patients preferred MIS-OLIF, which is less invasive, to MIS-TLIF. Clinical trial registration number: ChiCTR1800019443.

Luteoloside Inhibits IL-1ß-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration.

Intervertebral disk degeneration (IDD) is the major cause of low back pain (LBP), which affects 80% of the world's population. Interleukin 1 beta (IL-1ß) is a major inflammatory factor that accelerates disk degeneration, and IL-1ß levels increase in degenerative disks. It has recently been reported that luteoloside-a type of flavonoid glycoside-has anti-inflammatory properties. In the present study, we investigated the protective potential of luteoloside in IDD. We found that luteoloside maintains cell morphology and inhibits apoptosis (indicated by the reduced expression of cleaved caspase 3) in IL-1ß-treated nucleus pulposus (NP) cells. It also suppresses inflammatory mediators-nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)-in IL-1ß-treated NP cells. Furthermore, we found increased collagen II and aggrecan expression and reduced MMP13 and ADAMTS5 expression in luteoloside-treated NP cells in the presence of IL-1ß. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is involved in apoptosis, inflammation, and extracellular matrix (ECM) homeostasis. Mechanistic studies revealed that the NF-κB signaling pathway is inhibited by luteoloside, and Nrf2 is involved in the regulation of luteoloside in NF-κB signaling because Nrf2 knockdown reduced the suppressive effect of luteoloside on NF-κB signaling. We also established a puncture-induced rat IDD model and demonstrated that the persistent intraperitoneal injection of luteoloside ameliorates the progression of IDD. In conclusion, we demonstrated that luteoloside activates the Nrf2/HO-1 signaling axis and is a potential therapeutic medicine for IDD.

Building polyphenol and gelatin films as implant coating, evaluating from in vitro and in vivo performances.

Bone related implants have huge potential market in global. Improving the implant outcomes and probability of implant success are highly pursued to relieve the pain of patients and burden on native healthy system. There are growing evidence to support reactive oxygen species (ROS) directly involved in bone diseases and failure of implants. Taking advantage of the antioxidant property of tannic acid (TA) and biocompatibility of gelatin (Gel), the TA/Gel multilayer film was fabricated by layer by layer method, and the growing process of this film was monitored by QCM-D. The physical properties of TA/Gel film were further well characterized and modulated. In cellular test, TA/Gel multilayer film displayed good antioxidant properties under ROS stress environment (after H2O2 treatment flourscence intensity increased 38.9-fold for glasses, only ˜6-fold for (TA/Gel)8), facilitating cell attachment, fastening spreading at early stage and accelerating proliferation in beginning 2 day. Area per cell on (TA/ Gel)4-0.15 M is 1.5-fold higher than that on glass at 2 h, while it became 2.3-fold higher at 4 h. Moreover, these films performed both enhanced osteogenesis in vitro test and bone formation in vivo in the animal bone implanting model. Our results supported discovered the antioxidant coating played the critical role one the success of bone related implants, which could be particularly noted in the future implant design. And the strategy applied here, utilizing the interactions between polyphenol and proteins to construct multilayer film, will pave the way to fabricating an antioxidant coating.