Isoquercetin Ameliorates Osteoarthritis via Nrf2/NF-κB Axis: An In Vitro and In Vivo Study.

Osteoarthritis (OA) is a progressive joint disease characterized by extracellular matrix (ECM) degradation and inflammation, which is involved with pathological microenvironmental alterations induced by damaged chondrocytes. However, current therapies are not effective in alleviating the progression of OA. Isoquercetin is a natural flavonoid glycoside compound that has various pharmacological effects including anticancer, anti-diabetes and blood lipid regulation. Previous evidence suggests that isoquercetin has anti-inflammatory properties in various diseases, but its effect on OA has not been investigated yet. In this study, through western bolt, qRT-PCR and ELISA, it was found that isoquercetin could reduce the increase of ADAMTS5, MMP13, COX-2, iNOS and IL-6 induced by IL-1ß, suggesting that isoquercetin could inhibit the inflammation and ECM degradation of chondrocytes. Through nuclear-plasma separation technique, western blot and immunocytochemistry, it can be found that Nrf2 and NF-κB pathways are activated in this process, and isoquercetin may rely on this process to play its protective role. In vivo, the results of X-ray and SO staining show that intra-articular injection of isoquercetin reduces the degradation of cartilage in the mouse OA model. In conclusion, the present work suggests that isoquercetin may benefit chondrocytes by regulating the Nrf2/NF-κB signaling axis, which supports isoquercetin as a potential drug for the treatment of OA.

[Clinical study of double plate system in the treatment of complex proximal humeral fractures in the elderly].

OBJECTIVE: To explore the clinical outcomes of anteromedial combined with lateral locking plate for complex proximal humeral fractures in the eldery. METHODS: From June 2018 to October 2020, 30 patients who underwent surgical treatment for Neer grade 3 to 4 proximal humeral fractures, including 8 males and 22 females, aged from 51 to 78 years old with an average of (61.5±7.5) years old. Of them, 15 patients had fractures fixed with anteromedial combined with lateral locking plate(ALLP group), whereas 15 received internal fixation with proximal humerus locking plate only(PHLP group). The clinical data, simple shoulder test (SST), humeral head height loss, varus angle and shoulder range of motion were compared between the two groups. RESULTS: All fractures were healed. The follow-up time ranged from 12 to 24 months, with an average of(14.3±2.9) months. The operation time of ALLP group was longer than that of PHLP group (P<0.05). There was no significant difference in intraoperative blood loss between the two groups (P>0.05). There was no significant difference in SST score between the two groups at 1, 3 and 12 months after operation (P>0.05). In terms of radiographic measurement, there was no significant difference in humeral head height loss and varus angle between the two groups at 1 and 3 months after operation (P>0.05). At 12 months after operation, the height loss and varus angle of humeral head in ALLP group were lower than those in PHLP group (P<0.05). In shoulder range of motion, the range of forward elevation in ALLP group was larger than that in PHLP group 1 year after operation(P<0.05). There was no significant difference in external rotation between the two groups. CONCLUSION: Anteromedial combined with lateral locking plate in the treatment of complex proximal humeral fractures in the elderly can increase the stability of the medial column and obtain a good fracture prognosis. But there are also disadvantages such as longer operation time, so it should be individualized according to the fracture type of the patient.

Correlation Analysis Between Basic Diseases and Subsequent Vertebral Fractures After Percutaneous Kyphoplasty (PKP) for Osteoporotic Vertebral Compression Fractures.

BACKGROUND: Percutaneous kyphoplasty (PKP) is a widely accepted surgical treatment modality for painful osteoporotic vertebral compression fractures. The risk factors cause of subsequent vertebral fractures after PKP are debated. OBJECTIVES: To evaluate risk factors for the occurrence of new vertebral compression fractures after PKP. STUDY DESIGN: A retrospective study. SETTING: A single-center inpatient population. METHODS: A total of 921 patients (1,152 vertebrae) with PKP were investigated. Among those patients, 111 patients (155 levels) incurred refractures after PKP. RESULTS: The average bone mineral density was -3.27 in the "refracture"group and -3.00 in the "no fracture" group (P = 0.031). Morbidities of women were significantly higher in the "refracture" group (90.99%) compared with the "no fracture" group (81.73%) (P = 0.015). Among the basic diseases, several diseases (history of previously fracture, previously osteoporosis, gallstone disease, stomach disease, and ovariectomy) are associated with refractures after PKP (P < 0.05). And antiosteoporotic treatment (calcium + vitamin D or zoledronate) after PKP can also significantly reduce the occurrence of refracture (P < 0.000). In addition, logistic regression analysis also showed that most of the above contents had significant correlation with the refracture after PKP (P < 0.05), except for gallstone disease (P = 0.362). LIMITATIONS: Retrospective study, single center. CONCLUSION: Osteoporosis is the main cause of refracture after PKP. Elderly women were found to be more susceptible than elderly men to refracture. Patients with a history of previously fracture, previously osteoporosis, stomach ulcer, and ovariectomy are more likely to be refracture. Antiosteoporosis treatment (calcium + vitamin D or zoledronate) after PKP can reduce the risk of refracture.

Osteoclastic miR-301-b knockout reduces ovariectomy (OVX)-induced bone loss by regulating CYDR/NF-κB signaling pathway.

Postmenopausal osteoporosis (PMOP) is a frequent bone disorder responsible for an increased risk of disability to millions of individuals in the world. For identifying novel and effective targets to treat this disease, it is essential to explore the underlying molecular mechanisms. MicroRNAs (miRNAs) have been widely investigated due to their involvement in the pathophysiology of bone loss. In this study, we attempted to elucidate the role of miR-301-b in murine osteoclastogenesis. We found that miR-301-b expression was increased in the bone tissues from PMOP patients, along with up-regulated nuclear factor of activated T cells c1 (NFATC1), which were confirmed in ovariectomy (OVX)-induced mouse bone specimens and bone marrow-derived macrophages (BMMs). Osteoclastogenesis was found to be obviously suppressed by miR-301-b inhibitor, whereas being further promoted in BMMs transfected with miR-301-b mimic. The animal studies showed that osteoclastic miR-301-b knockout markedly up-regulated the bone mass by reducing osteoclastogenesis. Mechanistically, we found that cylindromatosis (CYLD) was a direct target of miR-301-b at the post-transcriptional level during osteoclastogenesis. The enhanced expression of CYLD led to a reduction of phosphorylated nuclear factor κB (NF-κB), along with remarkably decreased tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Finally, osteoclastic miR-301-b ablation evidently inhibited OVX-induced osteoclastogenesis, exhibiting protective effects against bone loss in rodent animals. Therefore, results in the study reported an important mechanism for osteoclastogenesis progression regulated by miR-301-b/CYLD/NF-κB pathway, which may be an effective therapeutic target for PMOP treatment.

An analytical reconstruction model of the spread-out Bragg peak using laser-accelerated proton beams.

With the development of laser technology, laser-driven proton acceleration provides a new method for proton tumor therapy. However, it has not been applied in practice because of the wide and decreasing energy spectrum of laser-accelerated proton beams. In this paper, we propose an analytical model to reconstruct the spread-out Bragg peak (SOBP) using laser-accelerated proton beams. Firstly, we present a modified weighting formula for protons of different energies. Secondly, a theoretical model for the reconstruction of SOBPs with laser-accelerated proton beams has been built. It can quickly calculate the number of laser shots needed for each energy interval of the laser-accelerated protons. Finally, we show the 2D reconstruction results of SOBPs for laser-accelerated proton beams and the ideal situation. The final results show that our analytical model can give an SOBP reconstruction scheme that can be used for actual tumor therapy.