Current Medicinal Chemistry - Online First

This work provides preclinical in vitro studies of an innovative antimicrobial agent named pyridosept, belonging to the quaternary bis-ammonium salts and synthesized on the base of pyridoxine. Since the wide spread of pathogens with tolerance to both antibiotics and antiseptics challenges the development of new antimicrobials providing high efficiency against fungi and microorganisms with multiple resistance.

This work presents in vitro studies of pyridosept, such as antibacterial and antifungal activities (determination of minimal inhibitory concentration and quantitative suspension test method), as well as antibacterial activity of metal surface test, sporicidal and spermicidal activities, formation of resistance (to bacteria and fungi), Skin-PAMPA (study of membrane transdermal permeability), mutagenicity assays (in Ames test and SOS-chromotest), cytotoxicity (MTT-assay) and comet assay in human skin fibroblasts.

Pyridosept demonstrates advantageous antibacterial and antifungal activity in both suspension and metal surface tests; it has anti-SARS-CoV-2, spermicidal and sporicidal activities (comparable to chlorhexidine digluconate). On the other hand, it demonstrates a low frequency of bacterial resistance development (no more than 2-4-fold increase of the MIC in 30 passages, with MIC values fluctuating within 1-8 µg/ml for Gram-positive bacteria and 4-32 µg/ml for Gram-negative bacteria) and membrane transdermal permeability (Skin-PAMPA, 500-fold less compared to progesterone). While cytotoxicity (in MTT- and comet assay) of pyridosept is comparable with those for bezalkonium chloride and chlorhexidine, our results suggest that pyridosept represents an advantageous structure for the design of new antiseptics.

The information obtained during the studies demonstrated that pyridosept has a good efficacy and safety profile, which allows us to consider it as a potential antiseptic and disinfectant, for which it is necessary to conduct additional in vivo studies.

Myocardial infarction (MI) is a common critical syndrome in the late development of cardiovascular diseases (CVDs), and traditional Chinese Medicine (TCM) treatment has become an essential branch in this field.

This study aimed to use bibliometric methods to examine the research trajectory of TCM treatment of MI from 2007 to 2024 from a multidimensional perspective and analyse its characteristics, hotspots, and frontiers.

This study used the search formula TS OR TI OR AB OR A (“traditional Chinese medicine” or “Chinese medicine” or “TCM” or “traditional medicine, Chinese” or ” Chinese traditional medicine” or “Chinese medicine, traditional”) AND TS OR TI OR AB OR AK (“myocardial infarction” or “myocardial infarctions” or ” infarction, myocardial” or “infarctions, myocardial” or “myocardial infarct” or “MI”) to find the Web of Science Core Collection (WOSCC) of relevant studies from 01/01/2007 to 04/29/2024. Target literature records were analysed and graphed using CiteSpace, VOSviewer, and Scimago Graphica.

A total of 754 records were obtained and 399 records were finally retained after screening. Countries, institutions, authors, and journals were visually analyzed. The current research hotspots and frontiers included Salvia miltiorrhiza, ischemia-reperfusion injury, pathway, molecular docking, and network pharmacology.

This research study would enrich the researchers' understanding of the existing research methodology and future development trends and provide a more efficient research methodology for the research on the mechanism of action of TCM for the treatment of MI and its clinical trials.

We aimed to develop Ferroptosis-Related Gene (FRG) signatures to predict overall survival (OS) along with disease-free survival (DFS) in individuals with colorectal cancer (CRC).

Prediction of CRC prognosis is challenging. Ferroptosis constitutes a newly reported kind of cell death, and its association with CRC prognosis remains unexplored.

This research endeavored to establish a prognostic risk signature for colorectal cancer by leveraging ferroptosis-related genes (FRGs), with the objective of refining prognostic precision in clinical settings.

The clinical data and mRNA expression profiles were obtained from The Cancer Genome Atlas (TCGA) colorectal cancer cohorts. The Lasso algorithm was employed to develop the overall survival (OS) and disease-free survival (DFS) prediction models. These models were subsequently validated using independent data from GSE38832.

Our research unveiled a significant difference in the expression levels of 85% of ferroptosis-related genes (FRGs) between CRC tissues and paracancer tissues. Out of these, 11 prognostic genes were pinpointed through univariate Cox analysis. By employing two models, patients were stratified into low- and high-risk groups based on predicted risk scores, which were subsequently validated as independent prognostic factors via multivariate Cox analysis. The robustness of these models was further confirmed through Receiver Operating Characteristic (ROC) curve analysis. Functional enrichment analysis indicated a predominance of cancer-associated pathways in the high-risk group, including WNT signaling, along with variations in immune status between the two risk categories. Leveraging the Connectivity Map (CMap) database, a total of sixteen potential therapeutic drugs were identified. Additionally, in vitro experiments corroborated that Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1) was underexpressed in CRC and exhibited tumor suppressive properties. More specifically, FDFT1 may augment ferroptosis in CRC by modulating the expression of the Iron-Sulfur Cluster Assembly Enzyme (ISCU).

Our study highlighted the significance of ferroptosis-related genes in the pathogenesis of CRC and underscored the potential of ferroptosis-related gene-based risk signatures as valuable tools for improving prognostic accuracy and tailoring therapeutic strategies. However, the validity of these predictive models required further validation through real-world studies to ensure their reliability and applicability.

This study aimed to screen the potential phytochemicals derived from Asparagus racemosus (Shatavari) against Thymidylate Kinase (TMPK) and D9 decapping enzyme, which is the vital target of the monkeypox virus and helps in the host-pathogen interaction mechanism, using integrated docking, QSAR analysis, and a molecular dynamics approach.

The Monkeypox Virus (MPXV) is a recently emerging outbreak with ongoing infection cases. Drugs and vaccines for smallpox are being used to contain it. However, no specific drugs or vaccines are available to combat this infection.

The TMPK and D9 decapping enzymes were retrieved from the MPXV virus UK strain in FASTA format. Due to the unavailability of an experimentally determined structure, the 3D structure was modelled via SWISS-MODEL and further enhanced and validated. The structure was subjected to docking analysis with the derived phytochemicals from Asparagus racemosus using a maestro module. The potential inhibitors were examined via QSAR analysis. Additionally, through MD simulation 250ns, the stability was analyzed, and the MM-GBSA was employed to calculate the binding affinities.

The molecular investigation revealed asparoside-C (PubChem ID: 158598) and asparoside-D (PubChem ID: 158597) to be potential hits among others for both targets (TMPK and D9 decapping enzyme) compared to the reference drugs, i.e., tecovirimat, brincidofovir, and cidofovir, possessing antiviral and required bioactivity analyzed via the ADME and QSAR analyses. Moreover, the simulation study of over 250ns revealed strong stability, followed by RMSD, RMSF, etc. The free energy calculation via MM-GBSA exhibited strong affinities of asparoside-C and asparoside-D towards the TMPK and the D9 decapping enzyme according to their respective scores.

The docking, QSAR, and simulation investigation revealed dual-target inhibitors activity of phytochemicals from Asparagus racemosus towards the MPXV via targeting TMPK and D9 decapping enzyme. It has been observed that asparoside-D and asparoside-C can potentially combat MPXV.

Fat grafting procedures for body contouring and cosmetic reconstruction have received widespread attention.

In recent years, there has been an increase in post-fat grafting infections caused by Mycobacterium abscessus (MA), and there is a lack of representative and standardized murine models of infection; therefore, there has been limited research on the treatment of post-fat grafting MA infections. To overcome this challenge, we constructed an MA infection model after fat grafting.

By evaluating skin charge, dermatopathology, and inflammatory markers, we found that the fat graft + 1 × 10⁹ CFU/mL bacterial suspension infection group had significant inflammatory symptoms and elevated inflammatory factors on postoperative day 10.

The model construction process was simple and reproducible, which paves the way for further studies on the impact of MA pathogenesis and the efficacy of new treatments.