Current Medicinal Chemistry - Volume 27, Issue 30, 2020

Background: Human serum albumin (HSA), the most abundant protein in plasma, is a monomeric multi-domain macromolecule with at least nine binding sites for endogenous and exogenous ligands. HSA displays an extraordinary ligand binding capacity as a depot and carrier for many compounds including most acidic drugs. Consequently, HSA has the potential to influence the pharmacokinetics and pharmacodynamics of drugs. Objective: In this review, the structural determinants of drug binding to the multiple sites of HSA are analyzed and discussed in detail. Moreover, insight into the allosteric and competitive mechanisms underpinning drug recognition, delivery, and efficacy are analyzed and discussed. Conclusion: As several factors can modulate drug binding to HSA (e.g., concurrent administration of drugs competing for the same binding site, ligand binding to allosteric-coupled clefts, genetic inherited diseases, and post-translational modifications), ligand binding to HSA is relevant not only under physiological conditions, but also in the pharmacological therapy management.

Different natural and synthetic biodegradable polymers have been used in vaccine formulations as adjuvant and delivery system but have faced various limitations. Chitosan is a new delivery system with the potential to improve development of nano vaccines and drugs. However, chitosan is only soluble in acidic solutions of low concentration inorganic acids such as dilute acetic acid and dilute hydrochloric acid and in pure organic solvents, which greatly limits its application. Chemical modification of chitosan is an important way to improve its weak solubility. Quaternized chitosan not only retains the excellent properties of chitosan, but also improves its water solubility for a wider application. Recently, quaternized chitosan nanoparticles have been widely used in biomedical field. This review focuses on some quaternized chitosan nanoparticles, and points out the advantages and research direction of quaternized chitosan nanoparticles. As shown by the applications of quaternized chitosan nanoparticles as adjuvant and delivery carrier in vaccines, quaternized chitosan nanoparticles have promising potential in application for the development of nano vaccines in the future.

To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors. These studies focused on the structural (C, prM, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) of dengue virus as well as host factors as drug targets. Hence, this article provides an overall up-to-date review of the discovery of dengue virus inhibitors that are only targeting the structural and non-structural viral proteins as drug targets.

Chitosan oligosaccharides (COS), hydrolysed products of chitosan, are low-molecular weight polymers with a positive charge and good biocompatibility. COS have recently been reported to possess various biological activities, including hypoglycaemic, hypolipidaemic, antioxidantantioxidant, immune regulation, anti-inflammatory, antitumour, antibacterial, and tissue engineering activities, exhibiting extensive application prospects. Currently, the biological processes and mechanisms of COS are attractive topics of study, ranging from the genetic, molecular and protein levels. This article reviews the recent discoveries about COS, especially in metabolic regulation, immune function and tissue repair, providing important insights into their multiple biological activities, medical benefits, and therapeutic mechanisms.

Hyperuricemia, defined as the presence of elevated serum uric acid (sUA), could lead to urate deposit in joints, tendons, kidney and other tissues. Hyperuricemia as an independent risk factor was common in patients during the causation and progression of kidney disease. Uric acid is a soluble final product of endogenous and dietary purine metabolism, which is freely filtered in kidney glomeruli where approximately 90% of filtered uric acid is reabsorbed. Considerable studies have demonstrated that soluble uric acid was involved in the pathophysiology of renal arteriolopathy, tubule injury, tubulointerstitial fibrosis, as well as glomerular hypertrophy and glomerulosclerosis. In the review, we summarized the mechanistic insights of soluble uric acid related renal diseases.

Background: Long non-coding RNAs (lncRNAs), a type of regulatory RNAs, play a key role in numerous cellular pathways. Ectopic expression of this group of non-coding RNAs has been specified to be involved in numerous diseases. Moreover, the role of lncRNAs in the initiation and development of cancers including colorectal cancer (CRC) has been acknowledged. Objective: In the present review, the role of lncRNAs as prognostic and diagnostic biomarkers in CRC as well as the molecular mechanisms of their contribution to development of CRC has been addressed. Results: The presented studies have indicated the ectopic expression of various lncRNAs in CRC. Some lncRNAs which were considered as tumor suppressors were downregulated in the colorectal cancerous tissues compared with healthy controls; however, some with oncogenic effects were upregulated. LncRNAs contribute to tumor development via various molecular mechanisms such as epigenetically controlling the expression of target genes, interacting with miRNAs as their sponge, etc. Conclusion: LncRNAs that have been recognized as prognostic biomarkers may pave the way for clinical management to offer adjuvant treatments for patients with CRC.

The ocular surface structure and extraocular accessory organs constitute the ocular surface system, which includes the cornea, conjunctiva, eyelids, lacrimal organs, and lacrimal passages. This system is composed of, and stabilized by, the corneal epithelium, conjunctival cells, conjunctival goblet cells, lacrimal acinar cells and Tenon’s fibroblasts, all of which maintain the healthy eyeball surface system. Ocular surface diseases are commonly referred to corneal and conjunctival disease and external ocular disease, resulting from damage to the ocular surface structure. A growing body of evidence has indicated that abnormal activation of the KCa3.1 channel and Ca2+/ calmodulin-dependent kinase initiates ocular injury. Signaling pathways downstream of the irregular Ca2+ influx induce cell progression and migration, and impair tight junctions, epithelial transport and secretory function. In this overview, we summarize the current knowledge regarding ocular surface disease in terms of physical and pathological alteration of the ocular system. We dissect in-depth, the mechanisms underlying disease progression, and we describe the current calcium transport therapeutics and the obstacles that remain to be solved. Finally, we summarize how to integrate the research results into clinical practice in the future.