Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson’s disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases.
Psoriasis (PSO) is a common skin disease affecting approximately 1%–3% of the population, and the incidence rate is increasing yearly. PSO is associated with a dramatically increased risk of cardiovascular disease, the most common of which is atherosclerosis (AS). In the past, inflammation was considered to be the triggering factor of the two comorbidities, but in recent years, studies have found that lipid metabolism disorders increase the probability of atherosclerosis in patients with psoriasis. In this review, we discuss epidemiological studies, clinical treatment methods, risk factors, and lipid metabolism of psoriasis and atherosclerosis comorbidities.
17 August 2022 in Colloids and Surfaces B: Biointerfaces
Aedes albopictus (Skuse) is a vector of several arboviruses, such as dengue, chikungunya, West Nile, and Zika viruses. At present, the use of synthetic insecticides is the main vector control strategy. However, the widespread and long-term use of insecticides has aroused several problems, including insecticide resistance, environmental pollution, and non-target species effects, thereby encouraging researchers to search for new alternatives derived from natural products. In recent decades, essential oils (EOs) as natural alternatives to control mosquitoes have received increasing attention. In the initial larvicidal activity screen, two Rutaceae plants (Citrus aurantium and Citrus paradisi) EOs were selected and evaluated for killing Ae. albopictus larvae. The LC50 values of C. aurantium and C. paradisi EOs against Ae. albopictus were 91.7 and 100.9 ppm, respectively. The main components of C. aurantium EO include diethyl o-phthalate (37.32%), limonene (10.04%), and methyl dihydrojasmonate (6.48%). The main components of C. paradisi EO include limonene (60.51%), diethyl o-phthalate (11.75%), linalool (7.90%), and styralyl acetate (6.28%). Among these main components of the two EOs, limonene showed potent larvicidal activity, with the LC50 value of 39.7 ppm. The nanoemulsions of limonene were prepared and characterized. The duration of larvicidal activity was greater in the limonene nanoemulsions than when limonene was applied in solvent. This study demonstrates that EOs of plants in family Rutaceae are a potential resource to develop new larvicides, and nanoemulsification is an effective method for improving the physicochemical properties and efficacy of natural products as larvicides.
1 December 2021 in Journal of Biomedical Nanotechnology
This research was performed to optimize the enzymatic synthesis of mannosylated ligand with which to prepare mannosy-lated liposomes and investigate their bioactivity. Based on single-factor studies, lipase dose, substrate molar ratio (diester lauric diacid-cholesterol to mannose) and temperature were identified as significant parameters, and optimal reaction conditions were determined through response surface methodology (RSM) with central composite design. The optimum operating parameters, 61.23 mg of lipase, a substrate molar ratio of 5.36, and 56.64 °C temperature offered a predicted yield (71.11%) which was consistent with the actual yield (69.08%). Drug-free mannosylated liposomes were prepared film-dispersion. The characterizations of these liposomes showed that mannosylated liposomes were well-dispersible spherical particles with an average particle size of 142.3 nm, the polydispersity index of 0.16, and a zeta potential of −19.8 mV. Pyrogen examination, hemolytic studies and cytotoxicity assays revealed no substantial safety concern for drug-free mannosylated liposomes. Cellular uptake efficiency of mannosylated liposomes by HepG2 cells was significantly higher than that of unmodified liposomes, demonstrating that mannosylated ligands have a positive effect on liver targeting. Overall, mannosylated liposomes could be active drug delivery system for combatting the therapy of hepatic diseases.
19 November 2024 in Colloids and Surfaces A: Physicochemical and Engineering Aspects