Betulin Accelerated the Functional Recovery of Injured Muscle in a Mouse Model of Muscle Contusion.

Muscle contusion is an injury to muscle fibers and connective tissues. It commonly happens in impact events, and could result in pain, swelling, and limited range of motion. Diclofenac is one of commonly used nonsteroidal anti-inflammatory drugs to alleviate pain and inflammation after injury. However, it can potentially cause some side effects including gastrointestinal complications and allergy. Betulin is a lupine-type pentacyclic triterpenoid. It is showed to have valuable pharmacological effects, but the physiological effect of betulin on muscle contusion has not been reported. This study aimed to explore the therapeutic effects of betulin on muscle contusion that produced by the drop-mass method in mice. C57BL/6 mice were randomly assigned to control (no injury), only drop-mass injury (Injury), diclofenac treatment (Injury+diclofenac), and betulin treatment (Injury+betulin) groups. Injury was executed on the gastrocnemius of the right hind limb, and then phosphate-buffered saline (PBS), diclofenac, or betulin were oral gavage administrated respectively for 7 days. Results revealed that betulin significantly restored motor functions based on locomotor activity assessments, rota-rod test, and footprints analysis. Betulin also attenuated serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels after muscle injury. Neutrophil infiltration was alleviated and desmin levels were increased after betulin treatment. Our data demonstrated that betulin attenuated muscle damage, alleviated inflammatory response, improved muscle regeneration, and restored motor functions after muscle contusion. Altogether, betulin may be a potential compound to accelerate the repair of injured muscle.

Predicting the Poor Clinical and Radiographic Outcomes after the Anatomical Reduction and Internal Fixation of Posterior Wall Acetabular Fractures: A Retrospective Analysis.

Anatomical reduction is the fundamental principle of hip function restoration after posterior acetabular wall fractures (PWFs). Some patients exhibit poor outcomes despite anatomical reduction, and the prognostic factors leading to poor outcomes remain elusive. This study aimed to investigate the clinical and radiographic outcomes in patients with PWFs who had undergone anatomical reduction and internal fixation and to identify the predictors that impair clinical and radiologic outcomes. The clinical records of 60 patients with elementary PWFs who had undergone anatomical reduction and internal fixation between January 2005 and July 2015 were reviewed retrospectively. The Harris hip score (HHS) and modified Merle d'Aubigné clinical hip scores (MMAS) were used to evaluate the clinical outcome. Preoperative and final follow-up radiographs were cross checked to identify poor radiographic outcomes that included the presence of advanced osteoarthritis and osteonecrosis, as well as the need for conversion to total hip arthroplasty. Acetabular dome comminution was assessed from computerized tomography, and the outcomes were further evaluated according to the involvement of fragment comminution. The fracture comminution and age were negatively correlated with functional outcomes (correlation coefficients were -0.41 and -0.39 in HHS and MMAS, respectively) and were significantly related to the severity of osteoarthritis and osteonecrosis as well as the need for total hip arthroplasty. Regarding the radiographic factors, significantly worse post-operative HHS and MMAS were found in the fracture comminution group. In the subanalysis of the status of fracture comminution, patients with fragment comminution involving the acetabular dome had significantly lower functional scores than those with other fracture patterns. In conclusion, age, fracture comminution, and dome comminution were the prognostic indicators of advanced osteoarthritis and poor functional scores after the anatomical reduction and internal fixation of PWFs. We emphasized the relevance of acetabular dome comminution as an important contributing factor to clinical and radiographic outcomes.

Fistein Suppresses Human Osteosarcoma U-2 OS Cell Migration and Invasion via Affecting FAK, uPA and NF-ĸB Signaling Pathway In Vitro.

BACKGROUND/AIM: Evidence has indicated that fisetin induces cytotoxic effects in human cancer cell lines, including the inhibition of cell migration and invasion, however, the exact molecular mechanism of action of fisetin in human osteosarcoma cells remains unclear. MATERIALS AND METHODS: The anti-metastatic mechanisms of fisetin in human osteosarcoma U-2 OS cells were investigated in vitro. RESULTS: Fisetin reduced the viability of cells at different concentrations (2.5, 5 and 10 µM) as measured by flow cytometric assay. Fisetin suppressed cell mobility, migration and invasion of U-2 OS cells, as shown by wound healing assay and transwell filter chambers, respectively. The gelatin zymography assay showed that fisetin inhibited MMP-2 activity in U-2 OS cells. Results from western blotting indicated that fisetin reduced the levels of pEGFR, SOS-1, GRB2, Ras, PKC, p-ERK1/2, p-JNK, p-p-38, VEGF, FAK, RhoA, PI3K, p-AKT, NF-ĸB, uPA, MMP-7, MMP-9, and MMP-13, but increased GSK3ß and E-cadherin in U-2 OS cells after 48 h of treatment. CONCLUSION: Fisetin can be used in the future, as a target for the treatment of metastasis of human osteosarcoma cells.

Maslinic Acid Enhances Immune Responses in Leukemic Mice Through Macrophage Phagocytosis and Natural Killer Cell Activities In Vivo.

BACKGROUND/AIM: Maslinic acid (MA), a pentacyclic triterpene extracted from wax-like coatings of olives, has been shown to reduce cancer cell number through induction of autophagy and apoptosis in many human cancer cells including human leukemia HL-60 cells. In the present study, we investigated whether or not MA affects immune responses in a leukemia mouse model. MATERIALS AND METHODS: WEHI-3 cells were intraperitonealIy (i.p.) injected into normal BALB/c mice to develop leukemia. Mice were then treated by i.p. injection with MA at different doses (0, 8, 16 and 32 mg/kg) for 2 weeks. After treatment, all animals were weighed and blood, liver and spleen tissues were weighed. Blood or spleen both were used for determination of cell markers or phagocytosis, natural killer (NK) cell activities and T- and B-cell proliferation, respectively, by using a flow cytometric assay. RESULTS: MA did not significantly affect body, liver, and spleen weights. However, MA increased markers of T-cells (at 16 mg/kg treatment) and monocytes (at 32 mg/kg treatment), but reduced B-cell markers (at 8 mg/kg treatment); MA did not significantly affect cell marker of macrophages. Furthermore, MA increased phagocytosis by macrophages from peripheral blood mononuclear cells and peritoneal cavity at 32 mg/kg treatment and increased NK cell activity at target cell:splenocyte ratio of 25:1 but did not affect B- and T-cell proliferation. CONCLUSION: MA increased immune responses by enhancing macrophage phagocytosis and NK cell activities in leukemic mice.

Rotational Shortening of Collateral Ligament in TKR With Severe Deformity.

Instability of the knee joint after total knee replacement (TKR) is one of the most important reasons for revision TKR. Inadequate release or tightening of the collateral ligaments in the knee joint may cause instability and early failure. This study presents a case series study of a new technique for ligament balancing wherein the collateral ligament is detached from its origin and rotated (twisted) around its longitudinal axis to tighten the ligament before the origin is reattached to its original position. The surgical technique for collateral ligament tightening during TKR was performed on 6 patients with a deformed knee caused by osteoarthritis and rheumatoid arthritis. The range of motion, knee society score, and laxity of the patients' knee joint, after 7 months to 13 years of follow-up, were evaluated. The technique was successful, achieving good range of motion and satisfactory stability of the joint. Further evaluation in a larger number of cases and a comparative analysis with different techniques would further support the usefulness of this rotational ligamentoplasty technique.