The role of miRNAs in multiple sclerosis pathogenesis, diagnosis, and therapeutic resistance.

In recent years, microRNAs (miRNAs) have gained increased attention from researchers around the globe. Although it is twenty nucleotides long, it can modulate several gene targets simultaneously. Their mal expression is a signature of various pathologies, and they provide the foundation to elucidate the molecular mechanisms of each pathology. Among the debilitating central nervous system (CNS) disorders with a growing prevalence globally is the multiple sclerosis (MS). Moreover, the diagnosis of MS is challenging due to the lack of disease-specific biomarkers, and the diagnosis mainly depends on ruling out other disabilities. MS could adversely affect patients' lives through its progression, and only symptomatic treatments are available as therapeutic options, but an exact cure is yet unavailable. Consequently, this review hopes to further the study of the biological features of miRNAs in MS and explore their potential as a therapeutic target.

Potential of Caffeic Acid and 10-Dehydrogingerdione as Lipid Regulators Relevant to Their Inhibitory Effect on miR-122 and ATP Citrate Lyase Activity in Diabetic Hyperlipidemic Rats.

The present study aimed to illustrate the hypolipemic effect of 10-Dehydrogengardione (10-DHG) or caffeic acid (CA) with reference to the role of microRNA-122 (miR-122) and ATP citrate lyase (ACLY) activity. Diabetic hyperlipidemia was induced in rats, and then randomly classified into three groups. The first one received only a CCT-diet for 6 weeks and was referred to as the positive control. The other two groups received 10-DHG (10 mg/kg/day) or CA (50 mg/kg/day), orally for 6 weeks along with a CCT-diet. Another group of normal rats was included, received a normal diet, and was referred to as the negative control. Either 10-DHG or CA significantly decreased MiR-122 expression and appeared more remarkable in the CA group by 15.5%. The 10-DHG greatly enhanced phosphorylated form of AMP activated protein kinase (p-AMPK) activity, more than CA by 1.18-fold, while the latter exerted more inhibitory effect on ACLY, and fatty acid synthase (FAS) activities compared with 10-DHG (p < 0.05). Both drugs significantly decreased hydroxy methyl glutaryl coenzyme A (HMG-COA) reductase activity, which appeared more remarkable in 10-DHG, and significantly decreased triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) along with a high density lipoprotein cholesterol (HDL-C) increase. The 10-DHG ameliorated the hepatic tissue lesions greatly, more than CA. The 10-DHG or CA significantly inhibited MiR-122, hepatic FAS, and ACLY levels along with p-AMPK activation. This subsequently led to reduced plasma TG, cholesterol levels, and blood glucose improvement and, indeed, may explain their mechanisms as hypolipemic agents.

Lycopene ameliorates hyperlipidemia via potentiation of AMP-activated protein kinase and inhibition of ATP-citrate lyase in diabetic hyperlipidemic rat model.

AIM: The present study aimed mainly to demonstrate the metabolic effects of lycopene (LYC) or atorvastatin (ATOR) in diabetic hyperlipidemic rat model. MAIN METHODS: Rats were randomly classified into four groups; the first was fed normal chow diet (NC) while the other three groups received streptozotocin (STZ) along with CCT-diet. The second group received no treatment (diabetic hyperlipidemic control, DHC), the third one received ATOR (50 mg/kg/day) while the fourth one received LYC (20 mg/kg/day). Serum and tissue samples were collected for biochemical and histological evaluations. KEY FINDINGS: DHC rats demonstrated significant hyperglycemia, dyslipidemia, increased hepatic fatty acid synthetase (FAS), malondialdehyde (MDA), tumor necrosis factor- alpha (TNF-α), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase and ATP citrate lyase (ACLY). However, hepatic reduced glutathione (GSH) and phosphorylated form of AMP-activated protein kinase (AMPK-P) activities showed significant decreases. ATOR or LYC administration induced hypoglycemic and hypolipidemic effects; decreased hepatic levels of MDA, TNF-α, HMG-CoA reductase, ACLY and FAS along with GSH and AMPK-P increases. Histopathological findings showed clear correlation with the biomarkers results. SIGNIFICANCE: LYC demonstrated favorable significant effects regarding the biomarkers studied as compared to ATOR and may be expressed as a potent therapeutic agent of natural origin for hyperlipidemia complications either alone or in combination with other hypolipidemic drugs.