Compatibility of Achyranthes bidentata components in reducing inflammatory response through Arachidonic acid pathway for treatment of Osteoarthritis.

Achyranthes bidentate is a common traditional Chinese medicine (TCM) used in treating osteoarthritis (OA). The compatibility between effective components has now become a breakthrough in understanding the mechanism of TCM. This study aimed at determining the optimal compatibility and possible mechanism of Achyranthes bidentate for OA treatment. Results showed that the adhesion score of the OA group is higher than NC group, and showed a trend of down-regulation in the intervention group. The CHI3L1 and IL-1ß in joint fluid of the OA group was significantly increased compared to the sham operation group (NC group). Group G, I, and L exhibited significantly down-regulated CHI3L1, while groups C, F, I, K, and L exhibited reduced IL-1ß. Joint adhesion, damage in cartilage, and synovial tissue was found in the OA model, cartilage tissue was found recovered in groups I, J, and L, and synovial tissue was recovered in group G, I, and L. Thus, group I and L were chosen for metabolite analysis, and indole-3-propionic acid was slightly up-regulated, while koeiginequinone A, prostaglandin H2, and 1-hydroxy-3-methoxy-10-methylacridonew were down-regulated in group I and L. According to functional analysis, the arachidonic acid (AA) metabolic pathway is enriched. Down-regulated expression of vital proteins in the AA metabolism pathway, such as PGE2 and COX2 in group I and L were verified. In conclusion, Hydroxyecdysone, Oleanolic acid, Achyranthes bidentata polysaccharide at a compatibility of 0.03-µg/mg, 2.0-µg/mg, 20.0-µg/mg or 0.03-µg/mg, 2.0-µg/mg, 10.0-µg/mg, respectively, may be the optimal compatibility of Achyranthes bidentate.

Achyranthes bidentata extract protects chondrocytes functions through suppressing glycolysis and apoptosis via MAPK/AKT signaling axis.

Osteoarthritis (OA) is considered to be a joint-associated disorder and one of leading reasons for disability, however, potential mechanism has never been clarified. The purpose of this research was to evaluate protective-effects of Achyranthes Bidentata extracts (ABE) on chondrocytes function in osteoarthritis. We performed a systematic investigation of transcriptional and proteomic landscapes to identify the underlying mechanisms behind effects of ABE on chondrocytic functions. OA animal models were generated in the present research. Chondrocytes were isolated and cultured, and then prepared for GeneChip analysis. Two-dimensional gel electrophoresis and LC-MS/MS analysis were conducted to analyze samples. Quantitative real-time PCR (qRT-PCR) and western blotting were used to evaluate expression of protein kinase B (AKT), ß-tubulin and ß-action. Apoptosis and glycolysis pathway were significantly compromised in chondrocytes with ABE stimulation as revealed by both transcriptional and proteomic data. Consistently, ABE suppressed chondrocytes apoptosis and glycolytic activity in vitro through modulating multiple genes, such as Plk2, Casp1/12 and Cers1 as well as Pkm2, Eno1/3 and Pgk2. Mechanically, ABE activated MAPK signaling pathway and suppressed AKT signaling pathway, therefore, reducing the glycolysis to provide survival benefits. We extended our analysis by verifying insulin-like growth factor 1 (IGF-1) and MAP kinase 1 (MEK1) in chondrocytes function. Depletion of either IGF-1 or MEK1 impaired AKT expression and phosphorylation, leading to the enhanced chondrocyte apoptosis and reduced cell proliferation. In conclusion, our study provided systematic view and molecular basis for ABE to serve as potential intervention of OA via suppressing AKT signaling.

Association between cytokines and exosomes in synovial fluid of individuals with knee osteoarthritis.

Background: Cytokines in synovial fluid (SF) play a crucial role in knee osteoarthritis (KOA). Exosomes are nanovesicles that are abundant in SF and carry a large quantity of signaling molecules. The purpose of this study was to evaluate the cytokine profiles of SF-derived exosomes and try to explore its biological function.Methods: Twenty-four KOA patients who were scheduled for their first intra-articular injection or knee replacement surgery were enrolled and divided into the KL1-2 group and the KL3-4 group according to the Kellgren and Lawrence (KL) classification. SF was collected from the patient's knee for the isolation of exosomes. A multiplex cytokine assay was performed to detect the 21 cytokines in the exosomes. The SF derived-exosomes were exposed to PBMCs and chondrocytes to assess their immunomodulatory potential.Results: Exosomes were successfully extracted from the SF, with an average diameter of 92 nm. Most cytokines were detectable in the SF-derived exosomes. Twelve inflammatory cytokines and eight chemokines were elevated in the exosomes of the KL3-4 group compared to that of the KL1-2 group (p < .05). A higher number of PBMCs were chemo attracted and the proliferation of chondrocytes was restrained by the SF-derived exosomes from the KL3-4 group in comparison with the KL1-2 group (p < .05).Conclusion: Our data indicated that most cytokines in SF are not only in a free form but also associated with and enriched in exosomes. Exosomes from end-stage KOA patients have a higher level of cytokines, especially chemokines, in comparison with the cytokine profiles of the soluble SF. SF-derived exosomes recruit inflammatory cells and inhibit cartilage proliferation, thus promoting joint degeneration. These data provide a new perspective for understanding the changes in the inner environment of KOA.

The predictive role of monocyte-to-lymphocyte ratio in osteoporosis patient.

Osteoporosis is a chronic, progressive disease in which early diagnosis is very important. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported as new predictors in inflammatory and immune diseases including osteoporosis. No studies have reported the relationship between monocyte-to-lymphocyte ratio (MLR) and osteoporosis patients.To investigated the ability of MLR to predict osteoporosis.Three hundred sixteen osteoporosis patients and 111 healthy control subjects were enrolled. Patients' laboratory and clinical characteristics were recorded. MLR, NLR, and PLR levels were calculated. The differences were compared and the diagnostic values of MLR were analyzed.There were 76 male and 105 female patients included, with a mean age of 56.57 ±â€Š9.95 years. The levels of MLR, NLR, and PLR in osteoporosis patients were all higher than those in healthy control subjects. The area under the curve of MLR was higher than those of NLR and PLR. Multivariate linear regression analysis showed that T-score was affected by age and MLR. MLR was positively correlated with C-reactive protein, erythrocyte sedimentation rate, red blood cell distribution width, age, sex, and inversely with hemoglobin. MLR and PLR levels were significantly higher in osteoporosis patients than in osteopenia patients (P < .05).The present study shows that MLR had a higher diagnostic value for osteoporosis. MLR may be a reliable, inexpensive, and novel potential predictor of osteoporosis.

PIM1, CYP1B1, and HSPA2 Targeted by Quercetin Play Important Roles in Osteoarthritis Treatment by Achyranthes bidentata.

AIM: Achyranthes bidentata is one of the most commonly used Chinese herbal medicines (CHM) that is currently considered for the treatment of osteoarthritis. The purpose of this study was to reveal the mechanism of Achyranthes bidentata in osteoarthritis treatment based on the network pharmacology. METHODS: The effective components of Achyranthes bidentata were firstly screened out from the TCMSP database with ADME property parameters. Then, osteoarthritis-related proteins targeted by the effective components were predicted based on the DrugBank and CTD databases. Subsequently, enrichment analysis and interaction network between targets of effective components and pathways were also studied. In addition, the differentially expressed genes (DEGs) of GSE55457 were used for validation of the osteoarthritis-related target proteins. Finally, the effective components-target molecular docking models were predicted. RESULTS: A total of 10 effective components were identified, of which kaempferol and quercetin had 1 and 29 targets, respectively. There were 26 target proteins of quercetin related to the osteoarthritis. These targets were mainly enriched in mitochondrial ATP synthesis coupled proton transport, cellular response to estradiol stimulus, and nitric oxide biosynthetic process. In addition, there were three common proteins, PIM1, CYP1B1, and HSPA2 based on the DEGs of GSE55457, which were considered as the key targeted proteins of the quercetin. CONCLUSION: The docking of PIM1-quercetin, CYP1B1-quercetin, and HSPA2-quercetin may play important roles during the treatment of osteoarthritis by Achyranthes bidentata.

Combining YESS and TESSYS techniques during percutaneous transforaminal endoscopic discectomy for multilevel lumbar disc herniation.

The authors retrospectively characterized the clinical outcomes of combining the Yeung endoscopic spine system (YESS) and transforaminal endoscopic surgical system (TESSYS) techniques during percutaneous transforaminal endoscopic discectomy (PTED) to treat multilevel lumbar disc herniation.PTED using both YESS and TESSYS was performed on 52 patients with multilevel lumbar disc herniations who had shown no apparent response to previous conservative treatments. Postsurgical follow-ups were conducted at weeks 1, 26, and 48. Patients' preoperative and postoperative performances were assessed by modified MacNab classification, Japanese Orthopedic Association (JOA) scores, Oswestry disability index (ODI), and visual analog scale (VAS), and compared with 34 and 45 patients who were treated only by YESS and TESSYS, respectively.The postsurgery surgeon-performed assessment showed satisfactory results in 98% of the YESS + TESSYS-treated cases. The average operative time was 116 ±â€Š23 minutes, intraoperative bleeding was 19 ±â€Š12 mL, and bed stay was 3 days. No complications occurred, including infection, nerve injury, or spinal canal hematoma. One week after surgery, the modified MacNab classifications of the patients were excellent in 45, good in 6, fair in 1, and poor in 0 (98% were excellent or good). JOA, ODI, and VAS scores for low back pain significantly improved relative to the preoperative assessment (P < .01) and had remained stable at 26 and 48 weeks.PTED that combined YESS and TESSYS techniques, depending on the predominant type of lumbar disc herniation at individual levels, is safe, minimally invasive, and effective.

[Unilateral fixation combined with interbody fusion for the treatment of lumbar degenerative instability via a paraspinal intermuscular approach under MAST Quadrant retractor].

OBJECTIVE: To study clinical effects of unilateral pedicle screw-rod system fixation combined with the single the cage of interbody fusion in the treatment of lumbar degenerative instability via paraspinal intermuscular approach under MAST Quadrant retractor. METHODS: From February 2010 to December 2011, 39 patients with lumbar degenerative instability after invalid conservative treatment were treated with unilateral fixation combined with interbody fusion via the paraspinal intermuscular approach under MAST Quadrant retractor. The indexes such as the operative time, blood loss, complications, VAS pain scores, JOA (subjective symptoms of low back pain,lower limb pain and numbness, sensory disturbance, movement disorders) scores, modified Macnab criteria for curative effect evaluation were observed before treatment, at the 1st month after treatment and the latest follow-up. The intervertebral fusion was studied on the X-ray at the latest follow-up. RESULTS: All the patients were followed up, and the mean during was (22.3 +/- 8.6) months. The operation time was (138 +/- 46) min, and the amount of bleeding was (335 +/- 152) ml. There were no complications such as cerebrospinal fluid leakage and spinal nerve injury during operation, and no incision infection after operation. The VAS pain score was reduced from preoperative 7.93 +/- 1.27 to 2.05 +/- 1.18 on the 1st month after operation and 1.89 +/- 0.42 at the latest follow-up. The JOA total score was improved from preoperative 1.59 +/- 0.42 to 8.86 +/- 0.37 on the 1st month and 9.02 +/- 0.29 at the latest follow-up. According to modified Macnab criteria, there were 17 cases got an excellent result, 19 good, 3 case fair. Thirty-five patients got intervertebral bony fusion at the latest follow-up. CONCLUSION: Unilateral pedicle screw-rod system fixation combined with single cage interbody fusion in the treatment of lumbar degenerative instability via paraspinal intermuscular approach under MAST Quadrant retractor is a safe, minimally invasive, satisfactorily effective methods to treat lumbar degenerative instability.

[Internal fixation combined with bone grafting through the injured pedicle for the treatment of thoracolumbar burst fractures via a paraspinal intermuscular approach under MAST Quadrant retractor].

OBJECTIVE: To study clinical effects of short-segment fixation and injured vertebra bone grafting through injured pedicle for the treatment of thoracolumbar burst fractures under MAST Quadrant retractor via a paraspinal muscle approach. METHODS: The data of 42 patients with thoracolumbar burst fractures treated from June 2009 to September 2012 were reviewed. There were 19 males and 23 females, with an average age of (55.2±11.9) years old. The mean injury time was (5.8±4.3) days. Fracture segments included T10 in 3 cases, T11 in 6 cases, T12 in 13 cases, L1 in 9 cases, L2 in 7 cases, and L3 in 4 cases. According to Denis classification, 9 patients were type A, 21 patients were type B, 5 patiens were type C, 5 patients were type D, and 2 patients were type E. All the patients were treated with short-segment pedicle screw-rod system fixation under MAST Quadrant via the paraspinal muscle approach. The operative time, blood loss, complications and the height of vertebra, kyphosis Cobb angle, VAS scores, JOA scores were measured before and after treatment. RESULTS: After treatment, the vertebral height and kyphosis Cobb angle were restored. Compared with preoperative results, postoperative vertebral height and kyphosis Cobb angle, VAS scores and JOA scores were all improved. But there was no statistically significance in vertebral height, kyphosis Cobb angle between postoperative at 1 week and 1 year. CONCLUSION: Internal fixation combined with injured vertebra bone grafting through the injured pedicle for the treatment of thoracolumbar burst fractures via the paraspinal intermuscular approach under MAST Quadrant is a safe, minimally invasive, effective and satisfactory method.