Cyaonoside A-loaded composite hydrogel microspheres to treat osteoarthritis by relieving chondrocyte inflammation.

Cyaonoside A (CyA), derived from the natural Chinese medicine, Cyathula officinalis Kuan, which was for a long time used to treat knee injuries and relieve joint pain in traditional Chinese medicine, showed an unclear mechanism for protecting cartilage. In addition, CyA was poorly hydrosoluble and incapable of being injected directly into the joint cavity, which limited its clinical application. This study reveals that CyA resisted IL-1ß-mediated chondrogenic inflammation and apoptosis. Next, transcriptome sequencing is used to explore the potential mechanisms underlying CyA regulation of MSC chondrogenic differentiation. Based on these findings, CyA-loaded composite hydrogel microspheres (HLC) were developed and they possessed satisfactory loading efficiency, a suitable degradation rate and good biocompatibility. HLC increased chondrogenic anabolic gene (Acan, COL2A, and SOX9) expression, while downregulating the expression of the catabolic marker MMP13 in vitro. In the osteoarthritis mouse model, HLC demonstrated promising therapeutic capabilities by protecting the integrity of articular cartilage. In conclusion, this study provides insights into the regulatory mechanisms of CyA for chondrocytes and proposes a composite hydrogel microsphere-based advanced therapeutic strategy for osteoarthritis.

[Expert consensus on integrated traditional Chinese and western medicine diagnosis and treatment for osteoporotic fractures].

Osteoporotic fractures represent the most severe complications of osteoporosis,characterized by insidious onset,high mortality and disability rates,and a steadily increasing incidence,imposing a significant socioeconomic burden. Western medicine has advantages in diagnosis and surgical interventions,while traditional Chinese medicine excels in holistic management and the restoration of bodily equilibrium. The integration of both traditional Chinese medicine (TCM) and western medicine emerges as an effective therapeutic strategy for osteoporotic fractures. In order to propagate the concept of integrated diagnosis and treatment,foster the advancement of integrated medical techniques for osteoporotic fractures,and establish standardized and normative protocols for disease prevention,diagnosis,and treatment,a consensus expert group,led by Geriatric Branch of Chinese Geriatrics Society,the Young Osteoporosis Group of Orthopedics Branch of Chinese Medical Association,Osteoporosis Group of Orthopedics Branch of Chinese Physician Association,and Osteoporosis Professional Committee of the Shanghai Society of Integrated Traditional Chinese and Western Medicine,was established. This group engaged in deliberations and formulated the "Expert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Osteoporotic Fractures" elucidating the concept of integrated medicine and offering recommendations in the domains of prevention,diagnosis,and treatment,with the aspiration of ameliorating the prognosis of osteoporotic fractures and enhancing the quality of life for these patients.

Diterbutyl phthalate attenuates osteoarthritis in ACLT mice via suppressing ERK/c-fos/NFATc1 pathway, and subsequently inhibiting subchondral osteoclast fusion.

Osteoarthritis (OA) is the most common arthritis with a rapidly increasing prevalence. Disease progression is irreversible, and there is no curative therapy available. During OA onset, abnormal mechanical loading leads to excessive osteoclastogenesis and bone resorption in subchondral bone, causing a rapid subchondral bone turnover, cyst formation, sclerosis, and finally, articular cartilage degeneration. Moreover, osteoclast-mediated angiogenesis and sensory innervation in subchondral bone result in abnormal vascularization and OA pain. The traditional Chinese medicine Panax notoginseng (PN; Sanqi) has long been used in treatment of bone diseases including osteoporosis, bone fracture, and OA. In this study we established two-dimensional/bone marrow mononuclear cell/cell membrane chromatography/time of flight mass spectrometry (2D/BMMC/CMC/TOFMS) technique and discovered that diterbutyl phthalate (DP) was the active constituent in PN inhibiting osteoclastogenesis. Then we explored the therapeutic effect of DP in an OA mouse model with anterior cruciate ligament transaction (ACLT). After ACLT was conducted, the mice received DP (5 mg·kg-1·d-1, ip) for 8 weeks. Whole knee joint tissues of the right limb were harvested at weeks 2, 4, and 8 for analysis. We showed that DP administration impeded overactivated osteoclastogenesis in subchondral bone and ameliorated articular cartilage deterioration. DP administration blunted aberrant H-type vessel formation in subchondral bone marrow and alleviated OA pain assessed in Von Frey test and thermal plantar test. In RANKL-induced RAW264.7 cells in vitro, DP (20 µM) retarded osteoclastogenesis by suppressing osteoclast fusion through inhibition of the ERK/c-fos/NFATc1 pathway. DP treatment also downregulated the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of the vacuolar (H+) ATPase V0 domain (Atp6v0d2) in the cells. In conclusion, we demonstrate that DP prevents OA progression by inhibiting abnormal osteoclastogenesis and associated angiogenesis and neurogenesis in subchondral bone.

Neobavaisoflavone inhibits osteoclastogenesis through blocking RANKL signalling-mediated TRAF6 and c-Src recruitment and NF-κB, MAPK and Akt pathways.

Psoralea corylifolia (P corylifolia) has been popularly applied in traditional Chinese medicine decoction for treating osteoporosis and promoting fracture healing since centuries ago. However, the bioactive natural components remain unknown. In this study, applying comprehensive two-dimensional cell membrane chromatographic/C18 column/time-of-flight mass spectrometry (2D CMC/C18 column/TOFMS) system, neobavaisoflavone (NBIF), for the first time, was identified for the bioaffinity with RAW 264.7 cells membranes from the extracts of P corylifolia. Here, we revealed that NBIF inhibited RANKL-mediated osteoclastogenesis in bone marrow monocytes (BMMCs) and RAW264.7 cells dose dependently at the early stage. Moreover, NBIF inhibited osteoclasts function demonstrated by actin ring formation assay and pit-formation assay. With regard to the underlying molecular mechanism, co-immunoprecipitation showed that both the interactions of RANK with TRAF6 and with c-Src were disrupted. In addition, NBIF inhibited the phosphorylation of P50, P65, IκB in NF-κB pathway, ERK, JNK, P38 in MAPKs pathway, AKT in Akt pathway, accompanied with a blockade of calcium oscillation and inactivation of nuclear translocation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1). In vivo, NBIF inhibited osteoclastogenesis, promoted osteogenesis and ameliorated bone loss in ovariectomized mice. In summary, P corylifolia-derived NBIF inhibited RANKL-mediated osteoclastogenesis by suppressing the recruitment of TRAF6 and c-Src to RANK, inactivating NF-κB, MAPKs, and Akt signalling pathways and inhibiting calcium oscillation and NFATc1 translocation. NBIF might serve as a promising candidate for the treatment of osteoclast-associated osteopenic diseases.

3D Interconnected Mesoporous Alumina with Loaded Hemoglobin as a Highly Active Electrochemical Biosensor for H2 O2.

Alumina is one of the most common and stable metal oxides in nature, which has been developed as a novel adsorbent in enrichment of biomolecules due to its excellent affinity to phosphor or amino groups. In this study, ordered mesoporous alumina (OMA) with interconnected mesopores and surface acidic property is synthesized through a solvent evaporation induced co-assembly process using poly(ethylene oxide)-b-polystyrene (PEO-b-PS) diblock copolymer as a template and aluminium acetylacetonate (Al(acac)3 ) as the aluminium source. The pore size (12.1-19.7 nm), pore window size (3.5-9.0 nm) and surface acidity (0.092-0.165 mmol g-1 ) can be precisely adjusted. The highly porous structure endows the OMA materials with high hemoglobin (Hb) immobilization capacity (170 mg g-1 ). The obtained Hb@OMA composite is used as an electrocatalyst of biosensor for convienet and fast detection of hydrogen peroxide (H2 O2 ) with a low H2 O2 detection limit of 1.7 × 10-8 m and a wide linear range of 2.5 × 10-8 to 5.0 × 10-5 m. Moreover, the Hb@OMA sensors show a good performance in real time detection of H2 O2 released from Homo sapiens bone osteosarcoma, indicating their potential application in complex biological processes.

[Advanced progress of main pharmacology activities of triptolide].

Triptolide is an active component in traditional Chinese medicine Tripterygium wilfordii. Currently, triptolide has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. Its main pharmacology efficacies include anti-inflammation, anti-tumor, and immunity suppression. Recent studies have also demonstrated triptolide's protective effect on cardiovascular diseases and osteoporosis. This paper summarizes the pharmacological efficacy of triptolide based on the advance in studies of triptolide.

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 clinical trials of initial observation on therapeutic effects of moxibustion for osteoarthritis of the knee: multi-center clinical effect].

OBJECTIVE: To compare therapeutic effects between moxibustion and infrared therapy for the treatment of knee osteoarthritis. METHODS: From January 2007 to June 2008 period, 65 patients with knee osteoarthritis were divided into treatment and control groups randomly uniform random number table generated from SAS statistical software. Among 35 patients in the treatment group, 17 patients were male and 18 patients were female, ranging in age from 45 to 75 years, with an average of (61.2+/-6.4) years; the course of disease ranged from 9 to 43 months, with a mean of (23.6+/-13.8) months; the preoperative Lysholm score ranged from 19 to 28 scores, averaged (24.3+/-3.3) scores. In the control group, there were 30 patients, including 13 males and 17 females, ranging in age from 47 to 79 years, with an average of (62.5+/-9.3) years; the course of disease ranged from 8 to 45 months, with a mean of (24.6+/-16.6) months; the preoperative Lysholm score ranged from 20 to 29 scores, averaged (25.9+/-3.0) scores. The patients in the treatment group were treated with moxibustion, and the patients in control group were treated with infrared therapy. All the patients were followed up for 4 weeks. The Lysholm scores were compared between the two groups. RESULTS: According to Lysholm score for clinical efficacy, treatment group got (87.5+/-5.6) scores and the control group were (85.9+/-3.5) scores, the Lysholm score of the treatment group was higher than that of the control group (P<0.05). Among pain score, joint flexion and extension score, joint stability score, and up and down stairs score, the pain and joint stability scores of patients in the treatment group were higher than those of control group (P<0.05). CONCLUSION: Compared with infrared therapy, moxibustion treatment for knee osteoarthritis can get better joint function, which is effect to alleviate the patient's pain, improve joint stability, improve the efficacy, and is valued to be promoted.

[Evaluation of the clinical effect of knee osteoarthritis treated with moxibustion according to WHOQOL-BREF].

OBJECTIVE: To investigate and research WHOQOL-BREF evaluation of the clinical effect of application of moxibustion for treatment of knee osteoarthritis, to provide clinical according for the treatment. METHODS: From January 2007 to June 2008, 90 cases of knee osteoarthritis were randomly divided into treatment group and control group. In treatment group there were 45 cases included 16 males and 29 females with an average age of (62.5 +/- 7.4) years; the average course was (26.5 +/- 14.6) months; Lysholm score of knee function before treatment was (65.5 +/- 3.5) hours on average. In control group, there were 45 cases included 11 males and 34 females with an average age of (62.5 +/- 9.3) years;the average course was (24.6 +/- 16.6) months; Lysholm score of knee function before treatment was (66.3 +/- 2.3) hours on average. Applied Quality of Life Scale WHOQOL-BREF in line with the inclusion criteria of the study evaluation. While applied Lysholm scoring of knee joint for supporting the evaluation criteria. All data were statistical analyzed by package SPSS 11.5. RESULTS: Moxibustion was applied to treat the knee osteoarthritis and the quality of life was evaluated according to the WHOQOL-BREF scale score. The scores of the physical state, psychological state, as well as their own general health status of subjective feeling, and so on in treatment was significantly higher than that in control group (P < 0.05). According to Lysholm scoring, the score in treatment group was significantly higher than that of control group, too (t = 0.65, P < 0.05). CONCLUSION: Application of moxibustion for treatment of knee osteoarthritis is a simple, economical and practical, and can avoid the further development of the disease, but also to improve the joint function and improve quality of life.