Jin Cui

Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis

Osteoporosis is a metabolic bone disease characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content. The imbalance between osteogenesis by osteoblasts and osteoclastogenesis by osteoclasts contributes to the pathogenesis of postmenopausal osteoporosis. Estrogen withdrawal leads to increased levels of proinflammatory cytokines. Overactivated osteoclasts by inflammation play a vital role in the imbalance. Matrine is an alkaloid found in plants from the Sophora genus with various pharmacological effects, including anti‐inflammatory activity. Here we demonstrate that matrine significantly prevented ovariectomy‐induced bone loss and inhibited osteoclastogenesis in vivo with decreased serum levels of TRAcp5b, TNF‐α, and IL‐6. In vitro matrine significantly inhibited osteoclast differentiation induced by receptor activator for NF‐κB ligand (RANKL) and M‐CSF in bone marrow monocytes and RAW264.7 cells as demonstrated by tartrate‐resistant acid phosphatase (TRAP) staining and actin‐ring formation as well as bone resorption through pit formation assays. For molecular mechanisms, matrine abrogated RANKL‐induced activation of NF‐κB, AKT, and MAPK pathways and suppressed osteoclastogenesis‐related marker expression, including matrix metalloproteinase 9, NFATc1, TRAP, C‐Src, and cathepsin K. Our study demonstrates that matrine inhibits osteoclastogenesis through modulation of multiple pathways and that matrine is a promising agent in the treatment of osteoclast‐related diseases such as osteoporosis.—Chen, X., Zhi, X., Pan, P., Cui, J., Cao, L., Weng, W., Zhou, Q., Wang, L., Zhai, X. Zhao, Q., Hu, H., Huang, B., Su, J. Matrine prevents bone loss in ovariectomized mice by inhibiting RANKL‐induced osteoclastogenesis. FASEB J. 31, 4855–4865 (2017). www.fasebj.org

Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats - A possible new hydrogen resource for clinical use.

Hydrogen is a kind of noble gas with the character to selectively neutralize reactive oxygen species. Former researches proved that low-concentration of hydrogen can be used to ameliorating cerebral ischemia/reperfusion injury. Hydrogen electrolyzed from water has a hydrogen concentration of 66.7%, which is much higher than that used in previous studies. And water electrolysis is a potential new hydrogen resource for regular clinical use. This study was designed and carried out for the determination of safety and neuroprotective effects of water electrolysis-derived hydrogen. Sprague-Dawley rats were used as experimental animals, and middle cerebral artery occlusion was used to make cerebral ischemia/reperfusion model. Pathologically, tissues from rats in hydrogen inhalation group showed no significant difference compared with the control group in HE staining pictures. The blood biochemical findings matched the HE staining result. TTC, Nissl, and TUNEL staining showed the significant improvement of infarction volume, neuron morphology, and neuron apoptosis in rat with hydrogen treatment. Biochemically, hydrogen inhalation decreased brain caspase-3, 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine-positive cells and inflammation factors concentration. Water electrolysis-derived hydrogen inhalation had neuroprotective effects on cerebral ischemia/reperfusion injury in rats with the effect of suppressing oxidative stress and inflammation, and it is a possible new hydrogen resource to electrolyze water at the bedside clinically.

Controlled release of vancomycin from 3D porous graphene-based composites for dual-purpose treatment of infected bone defects

Infected bone defects (IBD) are a challenging problem in orthopedic practice. Biomaterials have attracted attention as a novel approach to overcome this challenge instead of using conventional strategies. Graphene, a two-dimensional carbon allotrope, has been shown to possess multiple advantages, such as osteogenesis-promoting activity, a large surface area for drug delivery, and antibacterial activities. However, these attractive merits have not been entirely explored or introduced for the management of IBD. Herein, a novel approach using a vancomycin-laden, self-assembled, graphene-based material against IBD was developed, and the approach uses a single-stage bone graft instead of multiple procedures. Owing to the π–π bonding with graphene, vancomycin can be promptly delivered in the initial stage, followed by a sustained release, which ensures the rapid elimination of an infection and provides a durable pathogen revival inhibition via the inherent antibacterial activity of graphene. Moreover, the 3D porous structure incorporated with nano-hydroxyapatite (nHA) provided a biomimetic microenvironment favored by cell adhesion and osteogenic differentiation. Further evaluation of this system in an IBD animal model demonstrated prompt control of infection and promotion of bone regeneration. These results revealed the potential of this approach to be an effectual solution for IBD treatment and a new area of graphene application in the future.

Quality of Meta-analyses in Major Leading Gastroenterology and Hepatology Journals: A Systematic Review.

To appraise the current reporting methodological quality of meta‐analyses in five leading gastroenterology and hepatology journals, and to identify the variables associated with the reporting quality.

Matrine derivate MASM uncovers a novel function for ribosomal protein S5 in osteoclastogenesis and postmenopausal osteoporosis

Postmenopausal osteoporosis (POMP) is a public health problem characterized by decreased bone density and increased fracture risk. Over-activated osteoclastogenesis plays a vital role in POMP. Here we developed a novel bioactive compound MASM (M19) based on sophocarpine. Although it showed no significant effects on osteogenesis and adipogenesis for bone marrow-derived mesenchymal stem cells (BMSCs) in vitro, it could significantly inhibit RANKL/M-CSF induced osteoclastogenesis through suppressing NF-κB, MAPKs and PI3K/Akt pathways in vitro and ameliorate bone loss in ovariectomized mice in vivo. Ribosomal protein s5 (RPS5) has been identified as a target of M19 and regulates PI3K/Akt, NF-κB and MAPKs pathways in osteoclastogenesis. Overexpressions of RPS5 synergistically inhibited osteoclastogenesis with M19 while silencing RPS5 compromised M19 inhibitory effects on osteoclastogenesis in vitro. Among the three pathways, Akt plays a major role in M19 effects. The Akt activator SC79 partially reversed the inhibitory effects on osteoclastogenesis by M19 and RPS5-knocking-down. It indicates that RPS5 serves as a potential candidate target for inhibiting osteoclastogenesis and osteoporosis therapy and M19 is a promising agent for POMP treatment.

Effects of mesoporous calcium magnesium silicate on setting time, compressive strength, apatite formation, degradability and cell behavior to magnesium phosphate based bone cements

Mesoporous calcium magnesium silicate was doped into magnesium phosphate to fabricate magnesium phosphate based composite cements (MBC). The results showed that the setting time was significantly prolonged from 4 min to 11 min while the compressive strength decreased from 17 MPa to 9 MPa. In addition, the apatite formation ability improved in simulated body fluid (SBF) and degradation of the composite cements in Tris–HCl solution increased with the increase of m-CMS content of the MBC. Importantly, the MBC with excellent cytocompatibility remarkably promoted the MC3T3-E1 cells proliferation and differentiation, which depended on the m-CMS content. It can be suggested that MBC with good bioactivity, degradability and cytocompatibility has great potential to serve as implanted cements for bone defect filler and repairs.

Quality of meta-analyses in major leading orthopedics journals: A systematic review

BACKGROUND Meta-Analyses are the basis of professional and healthcare agencies recommendations and have a growing importance. Quality of meta-analyses has been investigated in some medical fields but to our best knowledge this issue remains under investigated in orthopedics. Therefore, we performed a systematic analysis to: 1) after the introduction of PRISMA statement as a comprehensive guideline and the use of the AMSTAR tool as the standard for sufficient review methodology, has the quality of MAs improved because of that? 2) have some general characteristics influenced the quality of MAs (country, funding source, number of authors)? MATERIAL AND METHODS We systematically searched the meta-analyses in the top four journals with the impact factor (2015) as following: JBJS, Osteoarthritis Cartilage Arthroscopy and Clin Orthop Relat Res from 2005 to 2008 and from 2012 to 2015. Likewise from 2012-2015, we also analyzed the meta-analyses from OTSR. Characteristics were extracted based on the PRISMA statement and the AMSTAR tool. Country, number of authors, funding source were also extracted. RESULTS A total of 154 meta-analyses were included in the present study. Score with PRISMA statement and the AMSTAR checklist were 20.86±3.04 out of a maximum of 27 and 7.86±1.55 out of a maximum of 11. The best journal was OTSR according to the PRISMA (23.06±1.92) and AMSTAR (9.13±0.87) scores. And the worst journal was Clin Orthop Relat Res according to the PRISMA score (19.4±2.70) and JBJS according to the AMSTAR score (6.78±1.65). Twelve items showed significant difference in the PRISMA statement, and five items in the AMSTAR checklist. Integral score of PRISMA statement and AMSTAR checklist has a significant difference between 2005-2008 and 2012-2015. The MAs reported from U.S. (56, 36.4%) were more than any other region in the world. And the MAs published by Asia/Oceania increased remarkably between these two period times [from (4, 10.8%) to (45, 38.5%)]. CONCLUSION This study showed that methodological reporting quality of meta-analyses in the major orthopedics journals has improved after the publication of the PRISMA statement. LEVEL OF EVIDENCE Level III.

Promotion of in vivo degradability, vascularization and osteogenesis of calcium sulfate-based bone cements containing nanoporous lithium doping magnesium silicate

Nanoporous lithium doping magnesium silicate (nl-MS) was introduced into calcium sulfate hemihydrate to prepare calcium sulfate composite (nl-MSC) bone cements. The introduction of nl-MS improved the in vitro degradability of nl-MSC cements, which could neutralize acidic degradable products of calcium sulfate and prevented the pH from dropping. The cements were implanted into the bone defects of femur bone of rabbits, and the results of histological and immunohistochemical analysis revealed that massive new bone tissue formed in the defects while the cements were degradable, indicating that the osteogenesis and degradability of the nl-MSC cements were much better than the control calcium sulfate dihydrate (CSD) cements. Furthermore, the positive expression of vascular endothelial growth factor and collagen type I for nl-MSC cements was higher than CSD, indicating that addition of nl-MS into the cements enhanced vascularization and osteogenic differentiation. The results suggested that the nl-MSC cements with good biocompatibility and degradability could promote vascularization and osteogenesis, and had great potential to treat bone defects.

The chinese version of achilles tendon total rupture score: cross-cultural adaptation, reliability and validity

AbstractBackgroundThe Achilles tendon Total Rupture Score (ATRS), which is originally developed in 2007 in Swedish, is the only patient-reported outcome measure (PROM) for specific outcome assessment of an Achilles tendon rupture.Purpose of this study is to translate and cross-culturally adapt Achilles tendon Total Rupture Score (ATRS) into simplified Chinese, and primarily evaluate the responsiveness, reliability and validity.MethodsInternational recognized guideline which was designed by Beaton was followed to make the translation of ATRS from English into simplified Chinese version (CH-ATRS). A prospective cohort study was carried out for the cross-cultural adaptation. There were 112 participants included into the study. Psychometric properties including floor and ceiling effects, Cronbach’s alpha, intraclass correlation coefficient, effect size, standard response mean, and construct validity were tested.ResultsThe mean scores of CH-ATRS are 57.42 ± 13.70. No sign of floor or ceiling effect was found of CH-ATRS. High level of internal consistency was supported by the value of Cronbach’s alpha (0.893). ICC (0.979, 95%CI: 0.984-0.993) was high to indicate the high test-retest reliability. Great responsive ness was proved with the high absolute value of ES and SRM (0.84 and 8.98, respectively). The total CH-ATRS score had very good correlation with physical function and body pain subscales of SF-36 (r = −0.758 and r = −0.694, respectively, p < 0.001), while poor correlation with vitality and role physical subscales of SF-36 (r = −0.033 and r = −0.025, respectively, p ≥ 0.05), which supported construct validity of CH-ATRS.ConclusionThis Chinese version of Achilles tendon Total Rupture Score (CH-ATRS) can be used as a reliable and valid instrument for Achilles tendon rupture assessing in Chinese-speaking population. Level of evidence II

Inhalation of Hydrogen of Different Concentrations Ameliorates Spinal Cord Injury in Mice by Protecting Spinal Cord Neurons from Apoptosis, Oxidative Injury and Mitochondrial Structure Damages

Background/Aims: Hydrogen selectively neutralizes reactive oxygen species (ROS) and ameliorates various ROS-induced injuries. Spinal cord injury (SCI) is a serious injury to the central nervous system, and secondary SCI is closely related to excessive ROS generation. We hypothesized that hydrogen inhalation ameliorates SCI, and the mechanism of action may be related to the protective effects of hydrogen against oxidative stress, apoptosis, and mitochondrial damage. Methods: Mechanically injured spinal cord neurons were incubated with different concentrations of hydrogen in vitro. Immunofluorescence staining and transmission electron microscopy were used to confirm the protective effects of hydrogen. ROS and related proteins were detected with dihydroethidium fluorescence staining, enzyme-linked immunosorbent assays, and western blotting. Terminal deoxynucleotidyl transferase dUTP nick end labeling assays, flow cytometry, and western blotting were used to detect neuronal apoptosis. ATP concentrations, Janus Green B staining, and mitochondrial permeability transition pore (mPTP) status were assessed to investigate mitochondrial damage. RNA sequencing was performed to screen potential target genes of hydrogen application. Hydrogen was administered to mice after spinal cord contusion injury was established for 42 days. The Basso Mouse Scale (BMS) and footprint analyses were used to assess locomotor functions, and immunofluorescence staining of the injured spinal cord segments was performed to detect oxidative stress status. Results: Spinal cord neurons were preserved by hydrogen administration after mechanical injury in a dose-dependent manner. ROS generation, oxidative stress injury-related markers, and the number of apoptotic neurons were significantly reduced after hydrogen treatment. The ATP production and mPTP function in injured neurons were preserved by hydrogen incubation. The expression levels of Cox8b, Cox6a2, Cox7a1, Hspb7, and Atp2a1 were inhibited by hydrogen treatment. BMS scores and the footprint assessment of mice with SCI were improved by hydrogen inhalation. Conclusions: Hydrogen inhalation (75%) ameliorated SCI in vivo and attenuated neuronal mechanical injuries in vitro, and its protective effect on spinal cord neurons was exerted in a dose-dependent manner. The underlying mechanisms included reducing ROS generation and oxidative stress, inhibiting neuronal apoptosis, and restoring mitochondrial construction and function. Cox8b, Cox6a2, Cox7a1, Hspb7, and Atp2a1 were identified as potential target genes of hydrogen treatment.