MicroRNA-455-3p inhibits osteosarcoma progression via HSF1 downregulation.

OBJECTIVE: This study was conducted to dissect the role and potential mechanism of microRNA (miR)-455-3p on osteosarcoma (OS) development. METHODS: miR-455-3p and HSF1 expression in OS tissues were detected by RT-qPCR and western blot. Later, gain- and loss-of-function assays were implemented in OS cells U-2OS and MNNG. The expression of apoptosis-related genes was measured by RT-qPCR and western blot. MTT, Transwell, scratch test, and flow cytometry were utilized to test OS cell viability, invasion, migration, and apoptosis. The targeting relationship between miR-455-3p and HSF1 was assessed with a dual-luciferase reporter gene assay. The transplantation tumor experiment in nude mice was utilized for in vivo confirmation. RESULTS: Downregulated miR-455-3p and upregulated HSF1 were displayed in OS tissues and cells. Mechanistically, miR-455-3p negatively targeted HSF1. MiR-455-3p inhibition or HSF1 overexpression increased MNNG and U-2OS cell proliferative, invasive, and migrating capabilities, while diminishing U-2OS cell apoptosis. Moreover, HSF1 overexpression negated the impacts of miR-455-3p upregulation on OS cell proliferative, invasive, migrating, and apoptotic abilities. Likewise, overexpressing miR-455-3p curtailed the growth of transplanted OS tumors through HSF1 repression. CONCLUSION: MiR-455-3p inhibits the development of OS cells by downregulating HSF1, highlighting the possibility of miR-455-3p as an innovative indicator of prognosis and a therapeutic target for OS.

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation.

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl4)-induced acute liver injury. Mice were intraperitoneally injected with CCl4 (0.15ml/kg). In CCl4+OCA group, mice were orally with OCA (5mg/kg) 48, 24 and 1h before CCl4. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl4-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl4-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl4-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl4-induced hepatic pro-inflammatory gene Tnf-α and Il-1ß. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl4-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl4-induced acute liver injury. These results suggest that OCA protects against CCl4-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury.

Bisphosphonates can prevent recurrent hip fracture and reduce the mortality in osteoporotic patient with hip fracture: A meta-analysis.

OBJECTIVE: This meta-analysis was conducted to investigate the efficacy of bisphosphonates for preventing recurrent hip fracture and reducing the mortality of elderly patient with hip fracture. METHODS: The databases of Pubmed, Embase and Cochrane Library were searched. All randomized or prospective matched controlled trials that assessed the efficacy of bisphosphonate for elderly patients with hip fracture were included. Two researchers independently extracted data of the included articles and assessed the methodological quality which was assessed based on Jadad scoring system or Newcastle-Ottawa scale. The second hip fracture incidence, mortality and complications were compared between bisphosphonates and control groups. RESULTS: Four studies including 3088 patients were included. Results showed that there were significant difference of second hip fracture (P<0.05) and mortality (P<0.05) between bisphosphonates group and control group. While no significant intergroup difference were observed for all complications. CONCLUSIONS: Bisphosphonates can prevent subsequent hip fracture, reduce the mortality, and does not increase the overall complications in elderly patients with hip fracture.

Protective effect of rosiglitazone against acetaminophen-induced acute liver injury is associated with down-regulation of hepatic NADPH oxidases.

The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. The aim of the present study was to investigate the effects of rosiglitazone (RSG), a synthetic PPAR-γ agonist, on acetaminophen (APAP)-induced acute liver injury. Male CD-1 mice were injected with APAP (300mg/kg). Some mice were pretreated with RSG (20mg/kg) 48, 24 and 1h before APAP injection. As expected, RSG pretreatment alleviated APAP-induced acute liver injury. Moreover, RSG pretreatment attenuated APAP-induced hepatic cell death and improved the survival. Although it did not affect hepatic cytochrome P450 (CYP)2E1 expression, RSG pretreatment attenuated reduction of hepatic glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd) and glutathione S-transferase (GST) activities, inhibited upregulation of hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-2 and NOX-4, and alleviated hepatic GSH depletion during APAP-induced acute liver injury. In addition, RSG pretreatment suppressed activation of hepatic nuclear factor kappa B (NF-κB) and extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling during APAP-induced acute liver injury. These results provide a novel mechanistic explanation for RSG-mediated protection against APAP-induced acute liver injury. The present results suggest that synthetic PPAR-γ agonists might be effective agents for preventing the progression of APAP-induced acute liver injury.

Hip arthroscopy versus open surgical dislocation for femoroacetabular impingement: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis aims to evaluate the efficacy and safety of hip arthroscopy versus open surgical dislocation for treating femoroacetabular impingement (FAI) through published clinical trials. METHODS: We conducted a comprehensive literature search using PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials databases for relevant studies on hip arthroscopy and open surgical dislocation as treatment options for FAI. RESULTS: Compared with open surgical dislocation, hip arthroscopy resulted in significantly higher Nonarthritic Hip Scores (NAHS) at 3- and 12-month follow-ups, a significant improvement in NAHS from preoperation to 3 months postoperation, and a significantly lower reoperation rate. Open surgical dislocation resulted in a significantly improved alpha angle by the Dunn view in patients with cam osteoplasty from preoperation to postoperation, compared with hip arthroscopy. This meta-analysis demonstrated no significant differences in the modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, or Hip Outcome Score-Sport Specific Subscale at 12 months of follow-up, or in complications (including nerve damage, wound infection, and wound dehiscence). CONCLUSION: Hip arthroscopy resulted in higher NAHS and lower reoperation rates, but had less improvement in alpha angle in patients with cam osteoplasty, than open surgical dislocation.

Rifampicin-Induced Hepatic Lipid Accumulation: Association with Up-Regulation of Peroxisome Proliferator-Activated Receptor γ in Mouse Liver.

Previous study found that rifampicin caused intrahepatic cholestasis. This study investigated the effects of rifampicin on hepatic lipid metabolism. Mice were orally administered with rifampicin (200 mg/kg) daily for different periods. Results showed that serum TG level was progressively reduced after a short elevation. By contrast, hepatic TG content was markedly increased in rifampicin-treated mice. An obvious hepatic lipid accumulation, as determined by Oil Red O staining, was observed in mice treated with rifampicin for more than one week. Moreover, mRNA levels of Fas, Acc and Scd-1, several key genes for fatty acid synthesis, were elevated in rifampicin-treated mice. In addition, the class B scavenger receptor CD36 was progressively up-regulated by rifampicin. Interestingly, hepatic SREBP-1c and LXR-α, two important transcription factors that regulate genes for hepatic fatty acid synthesis, were not activated by rifampicin. Instead, hepatic PXR was rapidly activated in rifampicin-treated mice. Hepatic PPARγ, a downstream target of PXR, was transcriptionally up-regulated. Taken together, the increased hepatic lipid synthesis and uptake of fatty acids from circulation into liver jointly contribute to rifampicin-induced hepatic lipid accumulation. The increased uptake of fatty acids from circulation into liver might be partially attributed to rifampicin-induced up-regulation of PPARγ and its target genes.

Rehabilitation protocol after arthroscopic rotator cuff repair: early versus delayed motion.

PURPOSE: To evaluate the effectiveness of early and delayed motion in rehabilitation after arthroscopic rotator cuff repair using a meta-analysis from randomized controlled trials. MATERIALS AND METHODS: Electronic searches of the CENTRAL, PUBMED, and EMBASE were used to identify randomized controlled trials that evaluated the effectiveness and safety of early and delayed motion for rehabilitation after arthroscopic rotator cuff repair. The methodological quality of the studies was assessed by the Cochrane Collaboration tool for assessing risk of bias. RESULTS: Four randomized controlled trials involving a total of 348 shoulders were included. Of these, two were rated as high quality and two were rated as moderate quality. No significant publication bias was detected by Egger's test and sensitivity analysis demonstrates a statistically robust result. Our meta-analysis indicated that early motion after arthroscopic rotator cuff repair resulted in a significantly greater recovery of external rotation from pre-operation to 3, 6, and 12 months post-operation (P < 0.05) and forward elevation ability from pre-operation to 6 months post-operation (P < 0.05), as compared to when motion was delayed. However, early motion resulted in non-significant excess (P > 0.05) in the rate of recurrence, compared to delayed motion. In addition, there were statistically higher rating scale of the American Shoulder and Elbow Surgeons (ASES) scores at 12 months post-operation (P < 0.05) and healing rates (P < 0.05) with delayed motion after arthroscopic rotator cuff repair, compared with early motion. CONCLUSION: Our meta-analysis included data from randomized controlled trials and demonstrated that delayed motion after arthroscopic rotator cuff repair resulted in higher healing rates and ASES scores than early motion. Alternatively, early motion increased range of motion (ROM) recovery, but also increased the rate of recurrence compared to delayed motion.

[Clinical effect of arthroscopically assisted repair and reconstruction for dislocation of the knee with multiple ligament injuries].

OBJECTIVE: To investigate the clinical outcomes of the treatment of knee dislocation with multiple ligaments injuries by anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction under arthroscopy and repair of the injured structures of the knee joint. METHODS: From July 2003 to August 2006, there were 24 patients with knee dislocation (19 males and 5 females), with the average age of 42 years (ranging from 20 years to 69 years), whose ACL and PCL were reconstructed under arthroscopy and whose collateral ligaments and other structures of the knee were repaired [8 with injuries of ACL, PCL, medial collateral ligament (MCL) and lateral collateral ligament (LCL); 12 with injuries of ACL, PCL and MCL; 4 with injuries of ACL, PCL and LCL]. There were 1 case with common peroneal nerve injury, 3 with medial meniscus injury and 7 with lateral meniscus injury. Every patient had single knee dislocation. The outcome was measured from the following aspects: range of the knee, complication, clinical improvement and Lysholm scoring. RESULTS: Twenty-four patients were followed up for 11 months to 36 months, with the average time of 25 months. Eleven patients (45.8%) recovered to the normal sports level and 13 (54.2%) patients' knee function improved significantly so that they could walk by themselves. Lachman test, anterior drawer test and posterior drawer test were negative in 24 patients. The side-to-side difference was less than 5 mm in 24 patients. There were 4 patients who had slight knee stiffness. One patient's feeling and sports function of the general peroneal nerve improved to the normal level. Lysholm scale of the knee function was 41.8 +/- 4.3 preoperatively and 87.0 +/- 6.0 postoperatively (P < 0.05). The movement ranges of the knee were (87.5 +/- 12.5) degrees preoperatively and (125.0 +/- 9.2) degrees postoperatively (P < 0.05). CONCLUSION: Reconstructing the ACL and PCL and repairing other structures of the knee is an effective method to treat dislocation of the knee.