Current Topics in Medicinal Chemistry - Volume 19, Issue 31, 2019

Background: microRNAs play a critical role in auto-immunity, cell proliferation, differentiation and cell death. miRNAs are present in all biological fluids, and their expression is essential in maintaining regular immune functions and preventing autoimmunity, whereas miRNA dysregulation may be associated with the pathogenesis of autoimmune and inflammatory diseases. Oral lichen planus (OLP) is an inflammatory disease mediated by cytotoxic T cells attack against epithelial cells. The present study aims to perform a specific microRNA expression profile through the analysis of saliva in this disease. Methods: The study group was formed by five patients (mean age 62.8±1.98 years; 3 females/2 males) affected by oral lichen planus and control group by five healthy subjects (mean age 59.8 years±2.3; 3 females/ 2 males); using a low-density microarray analysis, we recorded a total of 98 differentially expressed miRNAs in the saliva of patients with oral lichen planus compared to the control group. The validation was performed for miR-27b with qRT-PCR in all saliva samples of oral lichen planus group. Results: 89 miRNAs were up-regulated and nine down-regulated. In details, levels of miR-21, miR- 125b, miR-203 and miR15b were increased (p<0.001) in study group while levels of miR-27b were about 3.0-fold decreased compared to controls (p<0.001) of miR-27b expression in OLP saliva. QRTPCR validation confirmed the down regulation of miR-27b in all saliva samples. Conclusion: Collecting saliva samples is a non-invasive procedure and is well accepted by all patients. microRNAs can be readily isolated and identified and can represent useful biomarkers of OLP.

Background: West Syndrome is a rare epileptic encephalopathy involving infantile spasms, altered electroencephalographic pattern with hypsarrhythmia, and psychomotor development delay. It arises in paediatric patients, generally within the first year of life, in symptomatic or idiopathic form depending on the presence of hereditary features or not. Case Report: In this report it is described the case of a West syndrome patient affected by multiple caries, gingival enlargement, dental eruption abnormalities, high-arched palate and MIH, treated at the dental clinic of University of Bari “Aldo Moro”. Discussion: West patients present with multiple oral abnormalities, including altered eruption timing, teeth agenesis, teeth shape and position abnormalities, plaque and calculus accumulation, malocclusions and bad oral habits (mouth breathing, nails biting). Conclusion: West Syndrome patients’ oral hygiene is generally bad due to their motor difficulty and to their low compliance towards dentists, which entails general anaesthesia to perform dental treatment. West Syndrome pharmacological treatment is usually based on antiepileptic drugs and/or ACTH. These medications are well known for their ability to induce gingival enlargement, increasing the possibility of plaque accumulation and gingivitis development.

ST8Sia II (STX) is a highly homologous mammalian polysialyltransferase (polyST), which is a validated tumor-target in the treatment of cancer metastasis reliant on tumor cell polysialylation. PolyST catalyzes the synthesis of α2,8-polysialic acid (polySia) glycans by carrying out the activated CMP-Neu5Ac (Sia) to N- and O-linked oligosaccharide chains on acceptor glycoproteins. In this review article, we summarized the recent studies about intrinsic correlation of two polybasic domains, Polysialyltransferase domain (PSTD) and Polybasic region (PBR) within ST8Sia II molecule, and suggested that the critical amino acid residues within the PSTD and PBR motifs of ST8Sia II for polysialylation of Neural cell adhesion molecules (NCAM) are related to ST8Sia II activity. In addition, the conformational changes of the PSTD domain due to point mutations in the PBR or PSTD domain verified an intramolecular interaction between the PBR and the PSTD. These findings have been incorporated into Zhou’s NCAM polysialylation/cell migration model, which will provide new perspectives on drug research and development related to the tumor-target ST8Sia II.

Background: Before October 1846, surgery and pain were synonymous but not thereafter. Conquering pain must be one of the very few strategies that has potentially affected every human being in the world of all milestones in medicine. Methods: This review article describes how various general anesthetics were discovered historically and how they work in the brain to induce sedative, hypnosis and immobility. Their advantages and disadvantages will also be discussed. Results: Anesthesia is a relatively young field but is rapidly evolving. Currently used general anesthetics are almost invariably effective, but nagging side effects, both short (e.g., cardiac depression) and long (e.g., neurotoxicity) term, have reawakened the call for new drugs. Conclusion: Based on the deepening understanding of historical development and molecular targets and actions of modern anesthetics, novel general anesthetics are being investigated as potentially improved sedative-hypnotics or a key to understand the mechanism of anesthesia.

Gynostemma pentaphyllum (Thunb.) Makino (GpM) and its derivatives, especially gypenosides (Gyps), are widely used as safe and convenient natural herbal drugs for the treatment of many diseases for a long time, and Gyps have different oral bioavailability (OB) values and low ability to cross the blood-brain barrier (BBB). The effects of GpM and isolates on fibrosis, inflammation, oxidation, proliferation and migration are proved. GpM shows bidirectional regulation effect on proliferation, oxidation and apoptosis in tumor and non-tumor cells. GpM and its extractions can resist proliferation, activate oxidation and apoptosis in tumor cells and have opposite effects on non-tumor cells. We succinctly present some current views of medicinal value and potential therapeutic mechanisms of GpM and its derivatives.

Actinomycetes is an abundant resource for discovering a large number of lead compounds, which play an important role in microbial drug discovery. Compared to terrestrial microorganisms, marine actinomycetes have unique metabolic pathways because of their special living environment, which has the potential to produce a variety of bioactive substances. In this paper, secondary metabolites isolated from marine actinomycetes are reviewed (2013-2018), most of which exhibited cytotoxic, antibacterial, and antiviral biological activities.

Cilostazol is a unique platelet inhibitor that has been used clinically for more than 20 years. As a phosphodiesterase type III inhibitor, cilostazol is capable of reversible inhibition of platelet aggregation and vasodilation, has antiproliferative effects, and is widely used in the treatment of peripheral arterial disease, cerebrovascular disease, percutaneous coronary intervention, etc. This article briefly reviews the pharmacological mechanisms and clinical application of cilostazol.