Search

• Achyranthoside D is effective in relieving ACLT-MMx-induced osteoarthritis in rats. • Achyranthoside D inhibits NLRP3 inflammasome-triggered inflammation in rats. • Achyranthoside D attenuates IL-1β-induced chondrocyte loss in vitro. • Achyranthoside D inhibits NLRP3 inflammasome-triggered inflammation in vitro. • Achyranthoside D exerts anti-osteoarthritis effects via targeting Wnt3a. Achyranthes bidentata Blume (A. bidentata) is a common Chinese herb used to treat osteoarthritis (OA). Achyranthoside D (Ach-D) is a glucuronide saponin isolated from A. bidentata. To assess the mechanisms of action of Ach-D and its effects on OA. The effects of Ach-D were evaluated in rats underwent anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx) and in interleukin (IL)-1β-induced chondrocytes. Histological changes in rat cartilage tissues were detected using Safranin O-Fast green and haematoxylin-eosin staining. Immunohistochemical staining, qRT-PCR, ELISA, immunoblotting, and immunofluorescence were conducted to examine cartilage degeneration-related and inflammation-related factor expression. CCK-8, LDH assay, and EdU staining were performed to detect chondrocyte death. Ach-D dose-dependently reduced the Osteoarthritis Research Society International (OARSI) scores, alleviated cartilage injury, and decreased the serum concentrations of CTX-II and COMP in ACLT-MMx models. Ach-D increased the expression levels of collagen II and aggrecan and decreased the levels of cartilage degeneration-related proteins, ADAMTS-5, MMP13, and MMP3, in rat cartilage tissues. Additionally, nod-like receptor protein 3 (NLRP3)-related inflammation was reduced by Ach-D, as shown by the significantly inhibited expression levels of NLRP3, ASC, GSDMD, IL-6, TNF-α, IL-1β, and IL-18 in rat cartilage tissues. In primary rat chondrocytes, Ach-D protected against IL-1β-induced viability loss and LDH release. Wnt3a is the target protein of Ach-D. Mechanistically, Ach-D alleviated OA by inhibiting Wnt signalling. ACH-D may reduce inflammation and cartilage degeneration by inhibiting the Wnt signalling pathway, thereby reducing OA. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Over half the population of the world will suffer from moderate or severe low back pain (LBP) during their life span. Studies have shown that naringin, a major flavonoid in grapefruit and an active compound extracted from a Chinese herbal medicine (Rhizoma Drynariae) possesses many pharmacological effects.Purpose: The aim of this study was to evaluate the influence of naringin on the growth of degenerative human nucleus pulposus (NP) cells, and its repair effects on protein and gene expressions of the cells.Study Design/setting: This was an in vitro investigation of the human NP cells isolated from degenerated intervertebral discs that were interacted with various concentrated of naringin.Method: This study was exempted by the institutional Human Subjects Committee-2, University of Kansas School of Medicine-Wichita. Degenerative human NP cells were isolated from intervertebral discs of patients with discogenic LBP and cultured at 37°C with 5% CO2. The proliferation of NP cells was determined following treatment with various concentrations of naringin. The protein expressions of tumor necrosis factor-α (TNF-α) and Bone morphogenetic protein 2 (BMP-2) were tested using enzyme-linked immunosorbent assay. Aggrecan and type II collagen levels were measured by immunohistological staining. Further examination of the gene expression of aggrecan, Sox6, and MMP3 was performed after intervention with naringin for 3 days.Results: The human NP cells were successfully propagated in culture and stained positive with toluidine blue staining. Naringin effectively enhanced the cell proliferation at an optimal concentration of 20 µg/mL. Naringin treatment resulted in significant inhibition of TNF-α, but elevated protein expressions of BMP-2, collagen II, and aggrecan. Naringin also increased disc matrix gene activity including aggrecan and Sox6, and decreased the gene expression of MMP3.Conclusion: Naringin effectively promotes the proliferation of degenerative human NP cells and improves the recuperation of the cells from degeneration by increasing expression of aggrecan, BMP-2, and Sox6 while inhibiting the expression of TNF-α and MMP3. This study suggests that naringin may represent an alternative therapeutic agent for disc degeneration. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a common pathological condition that influences 20 % of women over 50 years of age. This condition decreases bone strength and increases the risk of bone fracture. Naringin is a major flavonoid found in grapefruit and an active compound extracted from a Chinese herbal medicine (Rhizoma Drynariae). Studies have shown that naringin possesses many pharmacological effects. The current study evaluated the influence of naringin on osteoblastic cell differentiation and proliferation, and assessed its therapeutic effects on a rat osteoporosis model. Method: The proliferation, differentiation, and function of rat bone marrow stromal cells (BMSCs) were determined following treatment with various concentrations of naringin. Ovariectomy (OVX)-induced osteoporotic rats were orally administered naringin daily at low, medium, and high dosages, while a control group received PBS for 2 months. Femoral X-ray images and microCT scans were used for bone mineral density (BMD) and BV/TV (bone volume/total volume) analyses, and histological assessments of left tibiae were employed to check for changes in trabecular thickness (Tb.Th) and trabecular space (Tb.Sp) in the groups. Results: Naringin was effective at enhancing the proliferation and osteogenic differentiation of BMSCs, and a concentration of 10 μg/ml prompted the highest levels of osteocalcin expression among the in vitro study groups. There appeared to be a delayed response pattern of BMSCs to the naringin treatment. Naringin also effectively reversed OVX-induced bone loss via increasing BMD, bone volume, and trabecular thickness. The medium dose (300 mg/kg) appeared to be the optimal dosage for delivering satisfactory therapeutic effects. Conclusion: Naringin promotes the proliferation and differentiation of BMSCs, and increases osteocalcin expression. Naringin also effectively reverses ovariectomy-induced osteoporosis in rats. The study suggests that naringin administration may represent an effective treatment for osteoporosis. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a quite common disease in both China and the United States with a reported indidence of 0.13-0.23%. The incidence of fracture in AS patients is higher compared with the ordinary population. Thoracolumbar fractures are the most common type with some complications. Treatment is usually focused on restoration of spinal stability because of the unique character of the AS spine. Surgical treatment is the primary treatment method and percutaneous fixation could be a minimally invasive option for most patients. To observe the clinical effect of thoracolumbar fracture of AS treated with posterior percutaneous long-segment internal fixation in 21 patients. Forty-one patients were divided into (1) a percutaneous group (21) and (2) an open surgery group (20). Posterior long-segment internal fixation with rod and screws was randomized and performed either openly or percutaneously. General data of the two groups were compared before the surgery and other parameters were compared during and after the surgery. SPSS 20 was used for statistics and P<0.05 was considered significant differences. Forty-one patients were included in the study. Operating time, blood loss during surgery, misplacement of screws, bed rest time after operation and VAS were measured. Forty-one patients diagnosed with thoracolumbar fractures of AS were treated from Nov. 2014 to Nov. 2018. All patients were divided into a percutaneous group and an open surgery group by means of a random table. Twenty patients underwent open fixation with long-segment screws and 21 others treated with percutaneous long-segment internal fixation. Reduction was performed with positioning and manipulation before sterilization. Small incisions were made according to the preoperation plan and then screws were inserted under fluorscopy. The rod must be shaped beforehand and then put into position. Operating time, blood loss, misplacement of pedicle screws and length of bed rest after operation were recorded. Imaging examinations were performed to evaluate the bone union, spinal cord injury and spinal column balance during follow up. All patients, followed up for 6 to 48 months (mean time 21.7 months), showed bony union and no signs of loosening or broken rods or screws. During surgery, there were no displaced screws or nerve injuries. No infections were found during or after the surgery; all surgical wounds healed. Significant differences were found for operating time, blood loss during the operation and length of bed rest after surgery within the two groups (P <0.05). No significant difference was found on visual analog score (VAS) after operation and improvement of Cobb angle of spinal kyphosis (P >0.05). As a minimally invasive surgery, posterior percutaneous long-segment internal fixation can achieve results similar to traditional open surgery in relieving patients' pain and correcting spinal kyphosis with less operating time, less blood loss during operation and less traumatic impact. It could be considered the first choice or a comparatively ideal method for the treatment of thoracolumbar fractures of AS patients. 3D print technique could be used for helping reduction and shaping of the rod. percutaneous fixation system (Approved for this indication). [ABSTRACT FROM AUTHOR]

Peripheral neuropathy (PN) is an incurable complication of multiple myeloma (MM) which adversely affects patients' quality of life. The important roles that Circular RNAs (circRNAs) play in tumor progression, and exosome-mediated intracellular communication has been recognized as a crucial factor in the pathogenesis of MM. However, the role of exosome-derived circRNAs (exo -circRNAs) in MM and MM-induced PN remains elusive. In this study, we aimed to investigate the correlation between serum exo-circRNAs and MM to preliminarily explore the role of exo-circRNAs in MM-related PN. A cohort of 25 MM patients and 5 healthy control (HC) individuals were enrolled in the study. High-throughput sequencing and qRT PCR validation of serum exo-circRNAs were used to generate the aberrantly expressed exo-circRNAs profiles. Bioinformatics analysis was done using GO, KEGG, miRanda, Targetscan and Metascape. Correlation analysis was conducted between chr2:2744228–2,744,407+ and clinical characteristics of PN. ROC curve, univariate and multivariate COX regression models were conducted to identify the prognostic potential of chr2:2744228–2,744,407+ in the MM-related PN. 265 upregulated circRNAs and 787 downregulated circRNAs, with at least a two-fold difference in expression level in MM patients vs HC, were screened. Bioinformatics analysis indicated that upregulated circRNAs had the potential to facilitate MM-related PN. Furthermore, PCR validated the abundant expression of chr2:2744228–2,744,407+ in the serum exosomes of 25 MM patients. Bioinformatics analysis indicated that chr2:2744228–2,744,407+ might induce MM related PN via the downstream miRNA and GRIN2B axis. Overexpressed chr2:2744228–2,744,407+ in the serum exosomes of MM patients might lead to the downregulation of hsa-miR-6829-3p, elevation of GRIN2B in the serum and PC12 cells, and inhibited cell viability. The correlation analysis indicated that the expression of chr 2:2744228–2,744,407+ was positively correlated with the clinical characteristics of PN. ROC curve, univariate and multivariate COX regression analysis identified that chr2:2744228–2,744,407+ is an independent prognostic factor in the MM related PN. We identified that the abnormal expression of the serum exo -circRNA was correlated with MM-related PN, implying that exo-circRNA has potential as a novel therapeutic target for MM related PN. • An abundant exo -circRNA profile was found in the serum of MM patients. • The upregulated exosomal chr2:2744228–2,744,407+ might have the potential to induce MM related PN via the ceRNA mechanism. • chr2:2744228–2,744,407+ was identified as the biomarker and independent prognostic indicator in MM related PN. [ABSTRACT FROM AUTHOR]