Tocotrienol-rich fraction (TRF) has demonstrated antiproliferative effect on prostate cancer (PCa) cells. To elucidate this anticancer property in PCa cells, this study aimed, first, to identify the most potent isomer for eliminating PCa cells; and second, to decipher the molecular pathway responsible for its activity. Results showed that the inhibitory effect of g-tocotrienol was most potent, which resulted in induction of apoptosis as evidenced by activation of pro-caspases and the presence of sub-G 1 cell population. Examination of the pro-survival genes revealed that the g-tocotrienol-induced cell death was associated with suppression of NF-kB, EGF-R and Id family proteins (Id1 and Id3). Meanwhile, g-tocotrienol treatment also resulted in the induction of JNK-signalling pathway and inhibition of JNK activity by a specific inhibitor (SP600125) was able to partially block the effect of g-tocotrienol. Interestingly, g-tocotrienol treatment led to suppression of mesenchymal markers and the restoration of E-cadherin and g-catenin expression, which was associated with suppression of cell invasion capability. Furthermore, a synergistic effect was observed when cells were cotreated with g-tocotrienol and Docetaxel. Our results suggested that the antiproliferative effect of g-tocotrienol act through multiplesignalling pathways, and demonstrated for the first time the anti-invasion and chemosensitisation effect of g-tocotrienol against PCa cells.

To date, the most effective cure for metastatic melanoma remains the surgical resection of the primary tumor. Recently, tocotrienol-rich-fraction has shown antiproliferative effect on cancer cells. To elucidate this anticancer property in malignant melanoma, this study aimed, first, to identify the most potent isomer for eliminating melanoma cells and second to decipher the molecular pathway responsible for its activity. Results showed that the inhibitory effect of gamma-tocotrienol was most potent, which resulted in induction of apoptosis as evidenced by activation of procaspases and the accumulation of sub-G1 cell population. Examination of the prosurvival genes revealed that the gamma-tocotrienol-induced cell death was associated with suppression of NF-kappaB, EGF-R, and Id family proteins. Meanwhile, gamma-tocotrienol treatment also resulted in induction of JNK signaling pathway, and inhibition of JNK activity by selective inhibitor was able to partially block the effect of gamma-tocotrienol. Interestingly, gamma-tocotrienol treatment led to suppression of mesenchymal markers and the restoration of E-cadherin and gamma-catenin expression, which was associated with suppression of cell invasion capability. Furthermore, synergistic effect was observed when cells were cotreated with gamma-tocotrienol and chemotherapy drugs. Together, our results demonstrated for the first time the anti-invasion and chemonsensitization effect of gamma-tocotrienol against human malignant melanoma cells.

CSA and AI do not appear to influence 24-month functional outcomes postoperatively and hence are not contraindications to arthroscopic rotator cuff repair.

Subchondroplasty is a relatively new joint preserving procedure, which involves the localized injection of calcium pyrophosphate bone substitute into the bone marrow lesion. The advent of magnetic resonance imaging (MRI) has greatly facilitated the identification of these bone marrow lesions. We investigated the clinical efficacy of subchondroplasty in the treatment of symptomatic bone marrow lesions in the knee, including knees with preexisting osteoarthritis. This study comprised of 12 patients whose knees were evaluated with standard radiographs and MRI to identify and localize the bone marrow lesions. They then underwent subchondroplasty under intraoperative radiographic guidance. Preoperative and postoperative visual analog scale (VAS) pain scores, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, and Knee Injury and Arthritis Outcome Scores (KOOS) were obtained. VAS scores improved significantly from 7.5 ± 1.8 before surgery to 5.2 ± 2.7 after surgery. This further improved to 2.1 ± 2.4 at the one-year follow-up. KOOS scores improved significantly from 38.5 ± 17.0 before surgery to 73.2 ± 19.0 at the one-year follow-up. WOMAC scores improved significantly from 47.8 ± 20.5 before surgery to 14.3 ± 13.2 at the one-year follow-up. Subchondroplasty offers an effective way to treat subchondral bone marrow lesions in the arthritic knee, resulting in improvement in symptoms and early return to activity. Long-term studies are required to evaluate if these benefits can last. This is a Level II study.

Abstract. The purpose of the current study is to evaluate the cardioprotective effects of purified Salvia miltiorrhiza extract (PSME) on myocardial ischemia / reperfusion injury in isolated rat hearts. Hearts were excised and perfused at constant flow (7 -9 ml ⋅ min −1 ) via the aorta. Non-recirculating perfusion with Krebs-Henseleit (KH) solution was maintained at 37°C and continuously gassed with 95% O 2 and 5% CO 2 . KH solution with or without PSME (100 mg per liter solution) was used after 30-min zero-flow ischemia for the PSME and control group, respectively. Left ventricular (LV) developed pressure; its derivatives, diastolic pressure, and so on were continuously recorded via a pressure transducer attached to a polyvinylchloride balloon that was placed in the left ventricle through an incision in the left atrium. PSME treated hearts showed significant postischemic contractile function recovery (developed pressure recovered to 44.2 ± 4.9% versus 17.1 ± 5.7%, P<0.05; maximum contraction recovered to 57.2 ± 5.9% versus 15.1 ± 6.3%, P<0.001; maximum relaxation restored to 69.3 ± 7.3% versus 15.4 ± 6.3%, P<0.001 in the PSME and control group, respectively). Significant elevation in end-diastolic pressure, which indicated LV stiffening in PSME hearts might have resulted from the excess high dose of PSME used. Further study will be conducted on the potential therapeutic value with lower dose of PSME on prevention of ischemic heart disease.