Current Pharmaceutical Design - Volume 28, Issue 34, 2022

Background: The odor and flavor produced by a complex mixture of chemical components with different amounts and thresholds constitute a unique property for food and Traditional Chinese Medicine (TCM). These compounds usually belong to mono- and sesquiterpenes, esters, lipids, and others. Objective: This review aimed to demonstrate the extraction method and reliable technology for identifying the compounds responsible for their odor and flavor. Methods: Existing techniques have been summarized for the analysis of taste and odor components and their characteristics, such as electronic nose (enose, EN) and electronic tongue (etongue, ET), which can separate high-quality food from low-quality and natural from artificial food in terms of unique odor and flavor. Results: Gas chromatography-olfactometry mass spectrometry (GC-O-MS), a technique derived from Gas chromatography mass spectrometry (GC-MS), coupled with human sense by Olfactory Detector Ports has been successfully applied for screening of the odor-producing components for the food or Chinese medicine. Conclusion: This current review provides some guidelines for quality evaluation of food or Chinese medicine.

Cancer nanotechnology takes advantage of nanoparticles to diagnose and treat cancer. The use of natural and synthetic polymers for drug delivery has become increasingly popular. Polymeric nanoparticles (PNPs) can be loaded with chemotherapeutics, small chemicals, and/or biological therapeutics. Major problems in delivering such therapeutics to the desired targets are associated with the lack of specificity and the low capacity of PNPs to cross cell membranes, which seems to be even more difficult to overcome in multidrugresistant cancer cells with rigid lipid bilayers. Despite the progress of these nanocarrier delivery systems (NDSs), active targeting approaches to complement the enhanced permeability and retention (EPR) effect are necessary to improve their therapeutic efficiency and reduce systemic toxicity. For this, a targeting moiety is required to deliver the nanocarrier systems to a specific location. A strategy to overcome these limitations and raise the uptake of PNPs is the conjugation with RNA aptamers (RNApt) with specificity for cancer cells. The site-directed delivery of drugs is made by the functionalization of these specific ligands on the NDSs surface, thereby creating specificity for features of cancer cell membranes or an overexpressed target/receptor exposed to those cells. Despite the advances in the field, NDSs development and functionalization are still in their early stages and numerous challenges are expected to impact the technology. Thus, RNApt supplies a promising reply to the common problem related to drug delivery by NDSs. This review summarizes the current knowledge on the use of RNApt to generate functionalized PNPs for cancer therapy, discussing the most relevant studies in the area.

Background: Most cannabinoids usually present several limitations when evaluating their clinical use, mainly related to the side effects they may cause at the central nervous system and other levels. In this regard, nanotechnology applied to the development of pharmacotherapeutic nanoformulations has become an attractive tool that allows taking advantage of the beneficial properties of multiple drugs while minimizing or avoiding their undesirable side effects. Nanotechnology is a relatively recent scientific field that involves the study, manipulation, development, and characterization of drug delivery systems at the nanoscale (1 to 1000 nm; 1 nm= 1x10-9 m). Usually, the physicochemical properties of matter at the nanoscale are significantly different compared to the matter at the macroscale, which provides several advantages over conventional therapeutic alternative types of organic and inorganic drug delivery nanosystems. Posology, size, composition, surface properties, and different physicochemical characteristics may directly or indirectly influence their pharmacodynamic and pharmacokinetic behavior and, consequently, their biomedical use. Purpose of Review: This mini-review summarizes the main recent findings on nanomedical strategies and applications for cannabinoid encapsulation, raising the possibility of transferring these advances to the therapy of addictions. Highlights Standpoints: The nano therapy significantly improves the pharmacokinetic and pharmacodynamic behavior of multiple active pharmaceutical ingredients with different limitations and disadvantages, thus enhancing the therapeutic compliance of patients. In general, cannabinoids loaded in nanoformulations offer greater efficacy, lower toxicity and more controlled/prolonged release than cannabinoids in free form.

Topoisomerase inhibitors are extensively used in cancer chemotherapy. In the process of identifying novel anticancer compounds, biological evaluations are crucial and include, among others, the use of in silico and in vitro approaches. This work aimed to present recent research involving the obtainment and in silico and in vitro evaluation of topoisomerase I, II, and double inhibitors, of synthetic and natural origin, as potential compounds against tumor cells, in addition to proposing the construction of a desirable enzyme catalytic site. Therefore, it was observed that most Topoisomerase I inhibitors presented medium to large structures, with a rigid portion and a flexible region. In contrast, Topoisomerase IIα inhibitors showed medium and large structural characteristics, in addition to the planarity of the aromatic rings, which are mitigated due to flexible rings but may also present elements that restrict conformation. Most compounds that exhibit dual inhibitory activity had relatively long chains, in addition to a flat and rigid portion suggestive of affinity for Topo I and a flexible region characteristic of selective drugs for Topo II. Besides, it is noticed that most compounds that exhibit dual inhibitory showed similarities in the types of interactions and amino acids when compared to the selective compounds of Topo I and II. For instance, selective Topoisomerase I inhibitors interact with Arginine364 residues, and selective Topoisomerase II inhibitors interact with Arginine487 residues, as both residues are targets for dual compounds.

Background: Acute kidney injury (AKI) is closely linked to the pathogenesis of sepsis. Oxidative stress can affect the development of AKI by increasing damage to renal tubular epithelial cells. Astragaloside IV (AS-IV) is a natural saponin widly verified beneficial for ameliorating sepsis-induced kidney injury. However, the underlying mechanisms of AS-IV on relieving oxidative stress in renal tubular epithelial cells are yet to be established. Purpose: We aimed to investigate whether AS-IV could attenuate mitochondrialdysfunction and apoptosis in renal tubular epithelial cells and reveal its underlying mechanisms. Methods: For the in vivo study, mice were divided into four groups (n=6): sham+saline, CLP+saline, CLP+ASIV- low dosage (5 mg/kg), CLP+AS-IV-high dosage (10 mg/kg), After 6 h or 24 h of treatment, the renal injuries were assessed based on related parameters of blood, protein and histopathological examination. Immunohistochemistry and ELISA were used to examine renal function. The molecular mechanism of AS-IV inhibited apoptosis and mitochondrial damage were monitored by flow cytometry and western blot analysis in HK-2 cells. Results: We found that AS-IV ameliorates renal vacuolization, brush border loss, mitochondrial ultrastructure changes in sepsis-induced AKI, and the apoptosis and oxidative damage were greatly mitigated by AS-IV (10 mg/kg)-treated group. Abnormal changes in mitochondrial morphology and mitochondrial membrane potential were alleviated, and the expression of mitochondrial complex protein I (NDUFB8) and mitochondrial complex protein II (SDHB8) increased with (10 mg/kg)-treated group. Tubular epithelial cell apoptosis in AS-IV (20 μM)-treated cells was reduced by the Bax and cleaved caspase3 pathway. Conclusion: These studies demonstrated that AS-IV protects against sepsis-induced kidney tubular injury by alleviating oxidative stress, mitochondrial dysfunction possibly associated with the restored cleaved caspase3 pathway.

Aims: To develop new anticancer agents based on ferrocene core. Background: Cancer has become the major cause of human death globally. The death caused by cancer mainly focuses on lung cancer, breast cancer, liver cancer, carcinoma of the colon, and rectum. Some small molecular inhibitors have been authorized by FDA for the treatment of cancer and several candidates are in different phases of clinical trials. However, cancer chemotherapy is still highly inadequate. Thus, it is indispensable to develop novel anticancer agents. Objective: Based on the previous good results, twelve novel structures of ferrocene formates bearing isoxazole moiety (3a-3l) were synthesized in this work for the development of anticancer agents. Methods: The target compounds were synthesized using Ferrocenecarboxylic acid and 3-[(R)-substitutedphenyl]- isoxazole-5-methanol catalyzed by DCC and DMAP. The structures of target compounds were characterized by ¹H NMR, ¹³C NMR, MS, HR-MS and XRD. Then, their preliminarily in vitro cytotoxicity against A549, HCT116, and MCF-7 cell lines was evaluated using the MTT method. Results: The results showed that most compounds exhibited moderate cytotoxicity against A549, HCT116, and MCF-7 cell lines compared with the positive control gefitinib. However, (3b, 3c, 3e, 3j, and 3k) simultaneously exhibited stronger inhibitory activity against A549, HCT116, and MCF-7 cell lines, which can be regarded as promising metal-based lead compounds for the development of anticancer agents. Conclusion: In this work, twelve new structures of ferrocene derivatives containing isozaole moiety were synthesized and their cytotoxicity against 549, HCT116, and MCF-7 cell lines was evaluated. (3b, 3c, 3e, 3j, and 3k) simultaneously exhibited stronger inhibitory activity towards A549, HCT116, and MCF-7 cell lines, which can be regarded as promising metal-based lead compounds for the development of anticancer agents.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes significant physical and psychological damage. Although researchers have gained a better understanding of the mechanisms of RA, there are still difficulties in diagnosing and treating RA. We applied a data mining approach based on machine learning algorithms to explore new RA biomarkers and local immune cell status. Methods: We extracted six RA synovial microarray datasets from the GEO database and used bioinformatics to obtain differentially expressed genes (DEGs) and associated functional enrichment pathways. In addition, we identified potential RA diagnostic markers by machine learning strategies and validated their diagnostic ability for early RA and established RA, respectively. Next, CIBERSORT and ssGSEA analyses explored alterations in synovium-infiltrating immune cell subpopulations and immune cell functions in the RA synovium. Moreover, we examined the correlation between biomarkers and immune cells to understand their immune-related molecular mechanisms in the pathogenesis of RA. Results: We obtained 373 DEGs (232 upregulated and 141 downregulated genes) between RA and healthy controls. Enrichment analysis revealed a robust correlation between RA and immune response. Comprehensive analysis indicated PSMB9, CXCL13, and LRRC15 were possible potential markers. PSMB9 (AUC: 0.908, 95% CI: 0.853-0.954) and CXCL13 (AUC: 0.890, 95% CI: 0.836-0.937) also showed great diagnostic ability in validation dataset. Infiltrations of 16 kinds of the immune cell were changed, with macrophages being the predominant infiltrating cell type. Most proinflammatory pathways in immune cell function were activated in RA. The correlation analysis found the strongest positive correlation between CXCL13 and plasma cells, PSMB9, and macrophage M1. Conclusion: There is a robust correlation between RA and local immune response. The immune-related CXCL13 and PSMB9 were identified as potential diagnostic markers for RA based on a machine learning approach. Further in-depth exploration of the target genes and associated immune cells can deepen the understanding of RA pathophysiological processes and provide new insights into diagnosing and treating RA.