Momordica charantia has been found to exhibit anticancer activity, in addition to its well-known therapeutic functions. We have demonstrated that the leaf extract of Momordica charantia (MCME) induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. In this study, a different susceptibility to MCME was found in human lung adenocarcinoma CL1 cells with different metastatic ability, leading to the significant difference of cell viability and invasiveness between MCME-treated CL1-0 and CL1-5 cells. MCME was found to upregulate the expression of Wnt-2 and affect the migratory and invasive ability of CL1 cells through suppressed MMP-2 and MMP-9 enzymatic activities. We proposed that MCME mediates inhibition against migration of CL1 cells by reducing the expression and activation of Src and FAK to decrease the expression of downstream Akt, β-catenin, and MMPs.

Background

Angiogenesis is essential for the progression of osteoarthritis (OA). Hepatocyte growth factor (HGF) is an angiogenic mediator, and it shows elevated levels in regions of OA. However, the relationship between HGF and vascular endothelial growth factor (VEGF-A) in OA synovial fibroblasts (OASFs) is mostly unknown.

Methodology/Principal Findings

Here we found that stimulation of OASFs with HGF induced concentration- and time-dependent increases in VEGF-A expression. Pretreatment with PI3K inhibitor (Ly294002), Akt inhibitor, or mTORC1 inhibitor (rapamycin) blocked the HGF-induced VEGF-A production. Treatment of cells with HGF also increased PI3K, Akt, and mTORC1 phosphorylation. Furthermore, HGF increased the stability and activity of HIF-1 protein. Moreover, the use of pharmacological inhibitors or genetic inhibition revealed that c-Met, PI3K, Akt, and mTORC1 signaling pathways were potentially required for HGF-induced HIF-1α activation.

Conclusions/Significance

Taken together, our results provide evidence that HGF enhances VEGF-A expression in OASFs by an HIF-1α-dependent mechanism involving the activation of c-Met/PI3K/Akt and mTORC1 pathways.

Plants are an invaluable source of potential new anti-cancer drugs. Momordica charantia is one of these plants with both edible and medical value and reported to exhibit anticancer activity. To explore the potential effectiveness of Momordica charantia, methanol extract of Momordica charantia (MCME) was used to evaluate the cytotoxic activity on four human cancer cell lines, Hone-1 nasopharyngeal carcinoma cells, AGS gastric adenocarcinoma cells, HCT-116 colorectal carcinoma cells, and CL1-0 lung adenocarcinoma cells, in this study. MCME showed cytotoxic activity towards all cancer cells tested, with the approximate IC50 ranging from 0.25 to 0.35 mg/mL at 24 h. MCME induced cell death was found to be time-dependent in these cells. Apoptosis was demonstrated by DAPI staining and DNA fragmentation analysis using agarose gel electrophoresis. MCME activated caspase-3 and enhanced the cleavage of downstream DFF45 and PARP, subsequently leading to DNA fragmentation and nuclear condensation. The apoptogenic protein, Bax, was increased, whereas Bcl-2 was decreased after treating for 24 h in all cancer cells, indicating the involvement of mitochondrial pathway in MCME-induced cell death. These findings indicate that MCME has cytotoxic effects on human cancer cells and exhibits promising anti-cancer activity by triggering apoptosis through the regulation of caspases and mitochondria.

Acute traumatic patellar dislocation is a common injury in the active and young adult populations. MRI of the knee is recommended in all patients who present with acute patellar dislocation. Numerous operative and non-operative methods have been described to treat the injuries; however, the ideal management of the acute traumatic patellar dislocation in young adults is still in debate. This article is intended to review the studies to the subjects of epidemiology, initial examination and management.

Introduction

Thrombin is a key factor in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of osteoarthritis (OA). Heme oxygenase (HO)-1 is a stress-inducible rate-limiting enzyme in heme degradation that confers cytoprotection against oxidative injury. Here, we investigated the intracellular signaling pathways involved in thrombin-induced HO-1 expression in human synovial fibroblasts (SFs).

Methods

Thrombin-mediated HO-1 expression was assessed with quantitative real-time (q)PCR. The mechanisms of action of thrombin in different signaling pathways were studied by using Western blotting. Knockdown of protease-activated receptor (PAR) proteins was achieved by transfection with siRNA. Chromatin immunoprecipitation assays were used to study in vivo binding of Nrf2 to the HO-1 promoter. Transient transfection was used to examine HO-1 activity.

Results

Osteoarthritis synovial fibroblasts (OASFs) showed significant expression of thrombin, and expression was higher than in normal SFs. OASFs stimulation with thrombin induced concentration- and time-dependent increases in HO-1 expression. Pharmacologic inhibitors or activators and genetic inhibition by siRNA of protease-activated receptors (PARs) revealed that the PAR1 and PAR3 receptors, but not the PAR4 receptor, are involved in thrombin-mediated upregulation of HO-1. Thrombin-mediated HO-1 expression was attenuated by thrombin inhibitor (PPACK), PKCδ inhibitor (rottlerin), or c-Src inhibitor (PP2). Stimulation of cells with thrombin increased PKCδ, c-Src, and Nrf2 activation.

Conclusion

Our results suggest that the interaction between thrombin and PAR1/PAR3 increases HO-1 expression in human synovial fibroblasts through the PKCδ, c-Src, and Nrf2 signaling pathways.

Background:

Open discectomy remains the standard method for treatment of lumbar disc herniation, but can traumatize spinal structure and leaves symptomatic epidural scarring in more than 10% of cases. The usual transforaminal approach may be associated with difficulty reaching the epidural space due to anatomical peculiarities at the L5–S1 level. The endoscopic interlaminar approach can provide a direct pathway for decompression of disc herniation at the L5–S1 level. This study aimed to evaluate the clinical results of endoscopic interlaminar lumbar discectomy at the L5–S1 level and compare the technique feasibility, safety, and efficacy under local and general anesthesia (LA and GA, respectively).

Methods:

One hundred twenty-three patients with L5–S1 disc herniation underwent endoscopic interlaminar lumbar discectomy from October 2006 to June 2009 by two spine surgeons using different anesthesia preferences in two medical centers. Visual analog scale (VAS) scores for back pain and leg pain and Oswestry Disability Index (ODI) sores were recorded preoperatively, and at 3, 6, and 12 months postoperatively. Results were compared to evaluate the technique feasibility, safety, and efficacy under LA and GA.

Results:

VAS scores for back pain and leg pain and ODI revealed statistically significant improvement when they were compared with preoperative values. Mean hospital stay was statistically shorter in the LA group. Complications included one case of dural tear with rootlet injury and three cases of recurrence within 1 month who subsequently required open surgery or endoscopic interlaminar lumbar discectomy. There were no medical or infectious complications in either group.

Conclusion:

Disc herniation at the L5–S1 level can be adequately treated endoscopically with an interlaminar approach. GA and LA are both effective for this procedure. However, LA is better than GA in our opinion.

We retrospectively analysed 106 consecutive traumatic humeral shaft fractures over a five-year period. The mechanism of injury, age, gender, fracture types, associated injury and the presence of injury to the radial nerve were reviewed. The incidence was about 10 per 100,000 per year; most were closed fractures in young males which had been sustained as a result of traffic accidents. The age–gender distribution was characterised by gradually increased incidence from the fifth decade in women, while it reached a peak at the third decade and decreased after the fifth decade in men. The results revealed different epidemiological features from previous studies. The epidemiology differs between ethnicity and country, and updating the epidemiological features of humeral shaft fractures may provide information for appropriate treatment programmes. This study documents the epidemiology of humeral shaft fracture in Taiwan, probably for the first time in this Asian community.

Background

Long-term alendronate therapy may lead to atypical femoral fractures in a very few patients. However, the management protocol to optimize fracture healing remains undetermined. The purpose of this study was to describe the time to union of atypical femoral fractures after surgical nailing in patients on long-term alendronate therapy, with continuation of alendronate or discontinuation of alendronate, and administration of bone-forming agents.

Findings

From January 2004 to December 2011, the records of patients at our institution on long-term alendronate therapy for more than 36 months and sustaining atypical femoral fractures that had undergone surgical nailing, with continuation of alendronate or discontinuation of alendronate and administration of bone-forming agents were reviewed.

During the 8-year study period, we treated 10 atypical femoral fractures with surgical nailing in 7 consecutive osteopenic or osteoporotic patients on long-term alendronate therapy for more than 36 months. There were no post-operative complications or needs for revision surgery. All fractures achieved union during follow-up. Mean union time was 23.5 months (range, 18–31 months) for 6 fractures with continuation of alendronate after surgery, and 4.5 months (range, 4–5 months) for 4 fractures with discontinuation of alendronate and administration of bone-forming agents after surgery.

Conclusions

Discontinuation of alendronate and administration of bone-forming agents after surgical nailing may promote union of atypical femoral fractures in patients on long-term alendronate therapy.