Melatonin ameliorates osteoarthritis rat cartilage injury by inhibiting matrix metalloproteinases and JAK2/STAT3 signaling pathway.

OBJECTIVE: To observe the effect of melatonin intervention on rat knee osteoarthritis (KOA) model and explore its mechanism. METHODS: A total of 81 Sprague-Dawley (SD) rats were employed. Haematoxylin and eosin (H&E) staining and safranin o-solid green staining were used to observe the changes of pathology in KOA, and inflammation factors in serum were detected by enzyme-linked immunosorbent assay (ELISA), type II collagen (Col-II) was detected by immunohistochemistry, chondrocyte apoptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL). The expression of matrix metalloproteinases (MMPs) and JAK2/STAT3 signaling were detected by western blot. RESULTS: Melatonin treatment ameliorated the histomorphology of knee joint in rats compared to the model group. The contents of TNF-α, IL-6, and IL-1ß in serum were decreased after melatonin treatment. In addition, compared to the model group, the positive expression of Col-II increased, the chondrocyte apoptosis decreased after melatonin treatment. Interestingly, the expression levels of MMP3, MMP9, MMP13, p-JAK2 and p-STAT3 decreased (p < 0.05). Importantly, melatonin combined with AG490 is significantly ameliorates histomorphology of knee joint, reduced cartilage loss compared with melatonin treatment alone. CONCLUSIONS: Melatonin treatment can effectively diminish the cartilage injury. Its mechanism may be related to protect the articular cartilage by reducing the release of inflammatory factors, inhibit the expression of MMPs and JAK2/STAT3 signaling.

Isoorientin ameliorates osteoporosis and oxidative stress in postmenopausal rats.

CONTEXT: Isoorientin has many biological activities, including antioxidant, anti-inflammatory, antitumor. However, the effect of isoorientin on postmenopausal osteoporosis remains unclear. OBJECTIVE: To evaluate the effect of isoorientin on postmenopausal osteoporosis. MATERIALS AND METHODS: Sprague-Dawley rats were divided into five groups (n = 5): sham, model, 17-ß-oestradiol (E2, 10 µg/kg/day), low-dose isoorientin (L-Iso, 50 mg/kg), and high-dose isoorientin (H-Iso, 100 mg/kg). The rats were ovariectomized, treated by gavage daily for 12 weeks, and serum and femur samples were collected. Bone mineral density, bone metabolism, and oxidative stress were assessed. H&E staining, immunohistochemistry, and western blotting were employed. RESULTS: Isoorientin improved the bone mineral density of the lumbar vertebrae (2.01 ± 0.05 g/cm3 in H-Iso group vs. 1.74 ± 0.07 g/cm3 in model group) and femur (1.46 ± 0.06 g/cm3 vs. 1.19 ± 0.03 g/cm3), increased the trabecular bone number (1.97 ± 0.03 vs. 1.18 ± 0.13) and thickness (0.27 ± 0.02 vs. 0.16 ± 0.03 mm). Isoorientin decreased the separation degree of trabecular bone, ameliorated bone histomorphology changes, and significantly improved the mechanical properties. Isoorientin diminished MDA (by 60%) and increased SOD (by 49.2%), and GSH-Px (by 159%) activity. Furthermore, osteoprotegerin (OPG), nuclear factor erythroid 2-like 2 (Nrf2), haem oxygenase (HO-1), NAD(P)H quinone dehydrogenase 1(NQO1), and oestrogen receptor 1(ESR1) protein expression increased, while receptor activator of nuclear factor-κB ligand (RANKL) protein expression decreased after treatment. CONCLUSIONS: Isoorientin ameliorates osteoporosis via upregulating OPG and Nrf2/ARE signalling, suggesting isoorientin maybe a potential therapeutic drug for PMOP.

[Lateral ligament reconstruction with autogenous partial peroneus longus tendon for chronic lateral ankle instability].

OBJECTIVE: To assess the effectiveness of lateral ligament reconstruction with autogenous partial peroneus longus tendon for chronic lateral ankle instability. METHODS: Between September 2014 and November 2018, 32 patients (32 sides) with chronic lateral ankle instability were treated with lateral ankle ligament reconstruction by using autogenous anterior half of the peroneus longus tendon. There were 25 males and 7 females, with an average age of 28.5 years (range, 20-51 years). The disease duration was 6-41 months (mean, 8.9 months). The preoperative Karlsson-Peterson ankle score was 53.7±9.7. The talar tilt angle was (14.9±3.7)°, and the anterior talar translation was (8.2±2.8) mm. Six patients combined with osteochondral lesion of talus and 4 patients combined with bony impingement. RESULTS: All incisions healed by first intention postoperatively. All patients were followed up 12-53 months (mean, 22.7 months). At last follow-up, the Karlsson-Peterson ankle score was 85.2±9.6; the talar tilt angle was (4.3±1.4)°; the anterior talar translation was (3.5±1.1) mm. There were significant differences in all indexes between pre- and post-operation ( P<0.05). Seventeen patients were very satisfied with the results, 10 patients were satisfied, 4 patients were normal, and 1 patient was unsatisfied. After operation, the ankle sprain occurred in 7 cases, the tenderness around the compression screws at calcaneus in 5 cases, the anterolateral pain of ankle joint over 6 months in 4 cases. No patient had discomfort around the reciepient sites. At last follow-up, the ultrasonography examination showed that there was no significant difference in the density and diameter between bilateral peroneus longus tendons in 12 cases. CONCLUSION: For chronic lateral ankle instability, the lateral ankle ligament reconstruction with the autogenous partial peroneus longus tendon is a safe and effective surgical option.

Negative feedback loop of ERK/CREB/miR-212-3p inhibits HBeAg-induced macrophage activation.

The activation of liver macrophages is closely related to liver injury after HBV infection. Our previous results demonstrated that HBeAg played a key role in inducing macrophage activation. As we all know, miRNAs are involved in the regulation of multiple immune cell functions. Meanwhile, we have shown that miR-155 positively regulates HBeAg-induced macrophage activation and accelerates liver injury. Subsequently, based on our previous miRNA sequencing results, we further evaluated the role of miR-212-3p called 'neurimmiR' in HBeAg-induced macrophages in this study. First, miR-212-3p expression was significantly elevated in HBeAg-treated macrophages. Meanwhile, we found up-regulation of miR-212-3p significantly decreased the production of cytokines, whereas knockdown of miR-212-3p held the opposite effect by gains and losses of function. Mechanically, although MAPK signal pathway, including ERK, JNK and p38, was activated in HBeAg-induced macrophages, only ERK promoted the expression of miR-212-3p via transcription factor CREB, which was able to bind to the promoter of miR-212-3p verified by ChIP assay. Moreover, we further indicated that up-regulated miR-212-3p inhibited HBeAg-induced inflammatory cytokine production through targeting MAPK1. In conclusion, miR-212-3p was augmented in HBeAg-stimulated macrophages via ERK/CREB signal pathway and the elevated miR-212-3p suppressed inflammatory cytokine production induced by HBeAg through targeting MAPK1.

Autogenous fibula graft and cannulated screw fixation to cephalic cut out after DHS fixation: a retrospective study.

BACKGROUND: This study aimed to explore the effect of the treatment through autologous fibula graft and hollow needle fixation to treat femoral head cutting after dynamic hip screw (DHS) fixation. METHODS: A total of 41 patients were admitted to the department of orthopedic trauma and received DHS fixation. Preoperative and postoperative harris score of hip function, limb shortening length and collodiaphysial angle between operation group (n = 11) and non-operation group (n = 13) were compared. RESULTS: There was no difference between the two groups before surgery (P > 0.05). There was a difference between the preoperative and postoperative in the operation group (P < 0.05). The excellent and good rate of the hip function score in patients 6 months after the operation was 55.6%. In the operation group, the hip function score increased after surgery (P < 0.001). Except for two groups of patients before operation, there was a difference in the limb shortening length and collodiaphysial angle between the operation group and non-operation group in other time points after surgery (P < 0.001). CONCLUSION: The application of the autogenous fibula graft and hollow nail fixation was effective in treating femoral head cutting after DHS fixation, and patients' subjective evaluation and objective indicators' outcomes of follow up were satisfactory, which was worthy of clinical application.

The effect of robot-navigation-assisted core decompression on early stage osteonecrosis of the femoral head.

BACKGROUND: The aim of the current paper is to evaluate the effects of robot-navigation-assisted core decompression compared with conventional core decompression surgery for early-stage osteonecrosis of the femoral head. METHODS: Twenty patients with a total of 36 hips who were diagnosed with Association Research Circulation Osseous stage 2 avascular necrosis of the femoral head and who received core decompression with or without robotic assistance were reviewed. The Harris hip score and visual analog scale score were used to assess clinical function. Intraoperative radiation exposure and operation time were used to evaluate the effectiveness of the robot-assisted system. RESULTS: At a mean follow-up of 26.4 months (24-36 months), the Harris hip score, visual analog scale score, and survival rate of the patients were similar between the conventional and robot-assisted groups. The guidewire insertion time, number of guidewire attempts, and radiation exposure during guidewire insertion were all significantly lower in the robot-assisted group than in the conventional group. CONCLUSIONS: Robot-assisted core decompression of the femoral head is as safe and effective as a conventional core decompression surgery. It can reduce operation time and decrease intraoperative radiation exposure.

Sulforaphane induces apoptosis and inhibits invasion in U251MG glioblastoma cells.

In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant and anti-tumor activities. In the present study, the viability inhibition effects of SFN in U251MG glioblastoma cells were analyzed by MTS. Morphology changes were observed by microscope. Apoptotic effects of SFN were evaluated by annexin V binding capacity with flow cytometric analysis. Invasion inhibition effects of SFN were tested by the invasion assay. The molecular mechanisms of apoptotic effects and invasion inhibition effects of SFN were detected by western blot and gelatin zymography. The results indicated that SFN has potent apoptotic effects and invasion inhibition effects against U251MG glioblastoma cells. These effects are both dose dependent. Taken together, SFN possessed apoptotic activity on U251MG cells indicated by increased annexin V-binding capacity, Bad, Bax, cytochrome C expression, and decreased Bcl-2 and survivin expressions. SFN inhibited invasion in U251MG cells via upregulation of E-cadherin and downregulation of MMP-2, MMP-9 and Galectin-3.