The emerging role of lipid nanosystems and nanomicelles in liver diseases.

Nanoparticles (NPs) exhibit remarkable potential in the diagnosis and treatment of various liver ailments, including primary liver cancer or hepatocellular carcinoma (HCC), liver cirrhosis, viral hepatitis, and alcoholic and non-alcoholic liver diseases. High surface area-to-volume ratio with distinct physicochemical and bio-pharmaceutical properties have contributed numerous benefits to NPs, such as high intracellular uptake and efficient drug delivery capabilities stemming from their ability to encapsulate a diverse range of drugs. Lipid-based nanosystems have demonstrated significant potential as reliable and efficient transport vehicles for a variety of actives, including small interfering RNA, targeting the liver, owing to their excellent in vivo compatibility, biodegradable nature, and non-toxic properties. Multiple aspects of various lipid-based materials, lipid nanosystems like solid lipid NPs, nanovesicles such as nanoemulsions, liposomes, and nanomicelles for liver-specific active targeting have been comprehensively reviewed. Ongoing and completed clinical trials of lipid nanosystems developed for HCC, hepatic fibrosis, and hepatitis are tabulated. Types of receptors and ligands typically used for active liver targeting in HCC are extensively discussed. The US FDA's recent approval for the use of Onpattro (Patisiran) injection to treat polyneuropathy in adult patients is indicative of the rapid development of lipid nanosystems employed for hepatic targeting. Nanoemulsions loaded with diagnostic imaging agents for multi-modal liver imaging were briefly discussed. Emerging technologies are being developed to integrate desirable properties of nanoparticles (NPs), including high stability, efficient drug loading, opsonization avoidance, active liver targeting, and facilitation of endosomal escape. Clinical translations of many lipid NPs for drug and gene therapy applications targeting different liver diseases are expected in the near future.

Venoms classification and therapeutic uses: a narrative review.

The mere glimpse of venomous animals has always terrified humans because of the devastating effects of their venoms. However, researchers across the globe have isolated therapeutically active ingredients from these venoms and continue to explore them for drug leads. These efforts lead to the discovery of therapeutic molecules that the US-FDA has approved to treat different diseases, such as hypertension (Captopril), chronic pain (Ziconotide), and diabetes (Exenatide). The main active constituents of most venoms are proteins and peptides, which gained more attention because of advancements in biotechnology and drug delivery. The utilization of newer screening approaches improved our understanding of the pharmacological complexity of venom constituents and facilitated the development of novel therapeutics. Currently, with many venom-derived peptides undergoing different phases of clinical trials, more are in pre-clinical drug development phases. This review highlights the various sources of venoms, their pharmacological actions, and the current developments in venom-based therapeutics.

Fenofibrate ameliorates letrozole-induced polycystic ovary in rats via modulation of PPARα and TNFα/CD95 pathway.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a prevalent endocrine health problem during the childbearing period that seriously affects fertility in females. Fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, showed beneficial effects in models of endocrine disturbances. Thus, we evaluated the potential therapeutic effect of fenofibrate in experimental PCOS. MATERIALS AND METHODS: Rats received oral fenofibrate (300 mg/kg/day) for three weeks following a three-week PCOS induction regimen using oral letrozole (1 mg/kg/day). We determined the changes in body weight, levels of serum testosterone, insulin, anti-Müllerian hormone (AMH), ovarian malondialdehyde (MDA), superoxide dismutase (SOD), and tissue tumor necrosis factor-alpha (TNFα) and CD95 protein expressions. The tissue expression of interleukin-10 (IL10) and PPARα genes was determined. RESULTS: Letrozole-treated rats showed successful induction of PCOS, confirmed by histopathology and significantly increased body weight, testosterone, insulin, AMH, and MDA, and decreased SOD. Ovaries of untreated PCOS rats showed increased TNFα and CD95 and decreased PPARα and IL10 expression. Administration of fenofibrate ameliorated the letrozole-induced PCOS changes. CONCLUSIONS: Fenofibrate-mediated amelioration of PCOS in rats is attributed partly to its antioxidant, anti-inflammatory, and anti-apoptotic properties and activation of PPARα.

Prevalence and types of genetic polymorphisms of CYP2C19 and their effects on platelet aggregation inhibition by clopidogrel.

OBJECTIVE: The current study was conducted to determine the distribution of genetic polymorphisms in CYP2C19 in Iraqi patients and their role in inter-individual variability of clopidogrel efficacy. PATIENTS AND METHODS: A prospective controlled study was done on 100 patients under high risk of cardiovascular diseases who started clopidogrel prophylactic therapy. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine the existence of the CYP2C19 gene mutation. Vasodilator-stimulated phosphoprotein (VASP) index baseline besides one-month post-therapy was analyzed by dual-color flow cytometry analysis. RESULTS: Eight gene mutations of CYP2C19 were found (*1/*1), (*1/*2), (*1/*3), (*1/*8), (*1/*17), (*2/*2), (*2/*4), and (*3/*3) with higher prevalent CYP2C19*1 gene. Homozygous CYP2C19*1 allele was shown to be the rapid metabolizer comparing to the heterozygous CYP2C19*1 allele, whereas, CYP2C19*2 and CYP2C19*3 were resistant alleles and were present in 28% of patients. The analysis of VASP phosphorylation produces accurate inter-individual response variability in platelets inhibition by antiplatelet drugs. CONCLUSIONS: In vitro gene analysis and VASP index improve the clinical outcome of a patient candidate to clopidogrel as prophylaxis in cardiovascular events.