The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas

Background Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood. Methods In this study, we analyzed TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouse glioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion. Results For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited. Conclusions Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.

Formulation Development and Evaluation of Liposphere of Poor Water Soluble Drug for Hyperlipidemia

Lipospheres offer a new approach to improve an aqueous solubility of BCS class-II drugs. Simvastatin is a third generation fibric acid derivative belonging to this class, employed clinically as a hypolipidemic agent to lessen the risk caused by atherosclerosis. An attempt was made to improve aqueous solubility of Simvastatin by aid of stearic acid and Paraffin oil. The factorial batches of the Simvastatin lipospheres were formulated by melt dispersion technique using 32 factorial design with variables X1- concentration of stearic acid and X2- concentration of paraffin oil and responses Y1 - % Drug Entrapment (% DE) and Y2 - % Drug Release (% DR). From the surface response graphs the optimized batch was formulated and evaluated for saturation solubility, in-vitro drug release studies. Significant improvement in the aqueous solubility of the drug in the Simvastatin lipospheres supports the applicability of lipospheres as a tool for improving aqueous solubility of the BCS class-II drugs. Keywords: Linospheres; Simvastatin; Drug release; Hyperlipidemic; Drug entrapment.

Lipid-Lowering Drug, Fenofibrate Combined with si-HOTAIR Can Effectively Inhibit the Proliferation of Gliomas

Background: Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood.Methods: In this study, we analyzed the TCGA database and found that there is a significant negative correlation between long non-coding RNA (lncRNA) HOTAIR and PPARα. Then we explored the molecular mechanism of lncRNA HOTAIR regulating PPARα from the level of in vitro cell lines and the level of nude mouse glioma model in vivo, and explored the effect of combined application of HOTAIR knocking down and fenofibrate treatment on glioma invasion.Results: For the first time, it was shown that after knocking down the expression of HOTAIR in gliomas, the expression of PPARα was significantly up-regulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both PPARα agonist, fenofibrate and si-HOTAIR; results showed that proliferation and invasion of glioma cells were significantly inhibited.Conclusions: Our results suggest that HOTAIR can negatively regulate the expression of PPARα, and the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.

Two Siblings with Familial Chylomicronemia Syndrome: Disease Course and Effectiveness of Early Treatment

There are no adequate data that evaluate the safety and effectiveness of lowering triglyceride levels in very young children. The authors report a family with two male siblings, 7 and 4 years old, affected by familial hyperchylomicronemia. The oldest was diagnosed at birth during evaluation of jaundice, and the youngest showed asymptomatic hypertriglyceridemia by 6 months of age. Due to high triglyceride levels, Gemfibrozil (a fibric acid derivative) was started at diagnosis. Close clinical followup and laboratory monitoring of these children showed no side effects from the drug, and the risk of acute pancreatitis was significantly reduced.

Rhabdomyolysis-Induced Acute Renal Failure Following Fenofibrate Therapy: A Case Report and Literature Review

Fenofibrate, a fibric acid derivative, is used to treat diabetic dyslipidemia, hypertriglyceridemia, and combined hyperlipidemia, administered alone or in combination with statins. Rhabdomyolysis is defined as a pathological condition involving skeletal muscle cell damage leading to the release of toxic intracellular material into circulation. Its major causes include muscle compression or overexertion; trauma; ischemia; toxins; cocaine, alcohol, and drug use; metabolic disorders; infections. However, rhabdomyolysis associated with fenofibrate is extremely rare. Herein we report a 45-year-old female patient who was referred to our department because of generalized muscle pain, fatigue, weakness, and oliguria over the preceding 3 weeks. On the basis of the pathogenesis and clinical and laboratory examinations, a diagnosis of acute renal failure secondary to fenofibrate-induced rhabdomyolysis was made. Weekly followups for patients who are administered fenofibrate are the most important way to prevent possible complications.

Severe hypertriglyceridaemia associated with human immunodeficiency virus and highly active antiretroviral therapy

We report two cases of severe hypertriglyceridaemia associated with human immunodeficiency virus infection and highly active antiretroviral therapy (HAART). The first patient, a 39-year-old man, developed moderate hypertriglyceridaemia (5·88 mmol/L) and hypercholesterolaemia (7·0 mmol/L) after 8 months of HAART. When his therapy was altered, triglyceride and cholesterol concentrations increased further to 15·9 and 10·9 mmol/L, respectively, after 6 weeks. The second patient, a 31-year-old man, presented with triglyceride and cholesterol concentrations of 16·2 and 5·7 mmol/L, respectively, following an 8-year history of HAART. Therapy was changed, but 1 month later the triglyceride concentration had increased to 39·4 mmol/L and the cholesterol concentration to 12·1 mmol/L. Both patients were managed by a change in HAART and the introduction of a fibric acid derivative. Although neither patient displayed any clinical symptoms associated with hypertriglyceridaemia, it is important to recognize such cases because of the associated risk of pancreatitis and coronary disease.

A Review of Combined Hyperlipidaemia and Its Treatment with Fenofibrate

Approximately 15% of myocardial infarction survivors <60 years of age have a plasma lipid abnormality defined as combined hyperlipidaemia. Patients with this condition are at substantial risk for future cardiovascular events. Combined hyperlipidaemia involves elevations in both plasma triglycerides and low-density lipoprotein (LDL) cholesterol and may share similarities with hyperapolipoproteinaemia, LDL-pattern B and the small LDL-pattern. Treatment is directed at reduction of LDL-cholesterol and plasma triglyceride values. Nicotinic acid and the fibric acid derivatives are useful therapeutic agents. Fenofibrate is a fibric acid derivative that lowers both triglycerides and LDL-cholesterol in combined hyperlipidaemia. In combined hyperlipidaemia, fenofibrate has been shown to reduce significantly plasma triglycerides by approximately 40%, LDL-cholesterol by 6%, and to increase high-density lipoprotein cholesterol by 15%. Apoproteins are favourably altered with increases in apoprotein-A, decreases in apoprotein-E and inconsistent decreases in apoprotein-B. Fenofibrate is well tolerated with primarily dermatological side-effects.