Current Pharmaceutical Design - Volume 29, Issue 14, 2023

The expression “as sure as night follows a day” emulates those certain cycles in the environment that are always stable. Circadian rhythms are a group of processes that occur within the body in synchronisation with the external factors in a 24 h cycle. Changes in lifestyle and work shifts have disrupted these stable rhythms, which is a leading cause of lifestyle diseases. Associations between these biological clocks and diseases are abundant. However, it is also known that certain drugs work more efficiently and have minimum toxicity when given during a particular phase of the circadian cycle. Chronotherapeutics focuses on treating diseases according to the endogenous processes which mediate xenobiotic metabolism and drug response at a cellular level. Therefore, treatment of those diseases that show aggravation of symptoms according to the circadian rhythms at a particular time is highly beneficial by chronotherapy. In this article, we have emphasised how the changes in rhythms caused diseases and how chronotherapeutic approaches such as controlled drug release technologies can be a better option for these circadian manipulations that seem to influence all types of disease conditions.

Numerous natural compounds have been identified that are able to induce apoptosis in cancer cells. These compounds have various chemical properties and are found in medicinal plants, vegetables, and fruits that are commonly consumed by humans. Phenols represent important compounds, which have been demonstrated to induce apoptosis in cancer cells, and some of the involved mechanisms have also been determined. The most important and abundant phenolic compounds are tannins, caffeic acid, capsaicin, gallic acid, resveratrol, and curcumin. Induction of apoptosis with the least or no toxicity to natural tissues is one of the useful effects of many plant-based bioactive compounds. Phenols, with anticancer potency at different degrees, serve to induce apoptosis through different pathways, including both extrinsic (Fas) and intrinsic (calcium release, ROS increase, DNA degradation, and mitochondrial membrane impairment). In this review, we report these compounds and their apoptosis-inducing mechanisms. Apoptosis or programmed cell death is a precise and systematic mechanism that is aimed at removing damaged or abnormal cells and is very useful to control, treat, and prevent cancer. Apoptotic cells are characterized by specific morphological features and molecular expression. In addition to physiological stimuli, there are many external factors that can be useful for inducing apoptosis. Also, these compounds can affect the regulatory proteins of the apoptotic pathways, such as the apoptotic proteins (Bid and BAX) and antiapoptotic proteins (Bcl-2). Taking these compounds and their molecular mechanisms into account can help use them in combination with chemical drugs and develop new drugs.

Introduction: Apoptosis and autophagy are the two fundamental processes involved in maintaining homeostasis, and a common stimulus may initiate the processes. Autophagy has been implicated in various diseases, including viral infections. Genetic manipulations leading to altered gene expression might be a strategy to check virus infection. Aim: Determination of molecular patterns, relative synonymous codon usage, codon preference, codon bias, codon pair bias, and rare codons so that genetic manipulation of autophagy genes may be done to curb viral infection. Methods: Using various software, algorithms, and statistical analysis, insights into codon patterns were obtained. A total of 41 autophagy genes were envisaged as they are involved in virus infection. Results: The A/T and G/C ending codons are preferred by different genes. AAA-GAA and CAG-CTG codon pairs are the most abundant codon pairs. CGA, TCG, CCG, and GCG are rarely used codons. Conclusion: The information generated in the present study helps manipulate the gene expression level of virus infection-associated autophagy genes through gene modification tools like CRISPR. Codon deoptimization for reducing while codon pair optimization for enhancing is efficacious for HO-1 gene expression.

Background: Fei Jin Sheng Formula (FJSF) is widely used in clinical treatment of lung cancer. But the underlying active ingredients and mechanisms are unclear. Objective: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro. Results: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona, quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage I patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate (MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2. Conclusion: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer.

Background: Nowadays, the emergence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains has dramatically restricted the treatment options against this microorganism. Aim: In this study, we aimed to discover new drug targets and inhibitors against S. aureus. Methods: This study consists of two major sections. In the upstream evaluation, after a comprehensive coreproteome analysis, essential cytoplasmic proteins with no similarity to the human proteome were selected. Then the S. aureus metabolome-specific proteins were selected, and novel drug targets were identified using the DrugBank database. In the downstream analysis, a structure-based virtual screening approach was performed to reveal potential hit compounds against adenine N1 (m¹A22)-tRNA methyltransferase (TrmK) using the StreptomeDB library and AutoDock Vina software. The compounds with a binding affinity > -9 kcal/mol were analyzed based on ADMET properties. Finally, the hit compounds were selected based on Lipinski’s rule of five (RO5). Results: Three proteins, including glycine glycosyltransferase (FemA), TrmK, and heptaprenyl pyrophosphate synthase subunit A (HepS1), were selected as feasible and promising drug targets based on PDB file availability and their essential role in the survival of the S. aureus. Finally, seven hit compounds, including Nocardioazine_ A, Geninthiocin_D, Citreamicin_delta, Quinaldopeptin, Rachelmycin, Di-AFN_A1 and Naphthomycin_ K were introduced against the binding cavity of TrmK, as a feasible drug target. Conclusion: The results of this study provided three feasible drug targets against S. aureus. In the following, seven hit compounds were introduced as potential inhibitors of TrmK, and Geninthiocin_D was identified as the most desirable agent. However, in vivo and in vitro investigations are needed to confirm the inhibitory effect of these agents on S. aureus.

An article was published in the journal "Current Pharmaceutical Design," Volume 13, No. 27, 2007, pp: 2781-2794 [1]. The first author is requesting an alteration in the name. Details of a correction are provided here. The original name published was Markus Galanski. The request is to change the name to Mathea Sophia Galanski. The original article can be found online at: https://www.eurekaselect.com/article/4836 We regret the error and apologize to readers.