Current Pharmaceutical Biotechnology - Online First

Antibiofilm agents serve as an essential tool in the fight against antibiotic resistance, and natural products provide a promising source for potential drug leads.

This study investigates the activity of twenty Bangladeshi medicinal plants against Staphylococcus aureus and Pseudomonas aeruginosa biofilms and predicts the interactions of selected phytochemicals from five of the best performing plants with the active sites of transcriptional regulatory proteins SarA of S. aureus and LasR of P. aeruginosa.

The plant extracts were tested by microtiter plate-based assay against S. aureus and P. aeruginosa biofilms. Molecular docking and molecular dynamics simulation (MD) were conducted using PyRx and GROMACS, respectively.

The best activity was identified for Cassia fistula and Ananas comosus, showing ≥ 75% inhibition of biofilm formation. ent-Epicatechin-(4α→8)-epiafzelechin (EEE) of C. fistula, cyanidin-3,3',5-tri-O-β-D-glucopyranoside (CTG) of A. comosus, and 7-O-(4-hydroxy-E-cinnamoyl)-spinoside of A. spinosus showed the best predictive binding affinity (-7.6, -7.6 and -7.7 kcal/mol, respectively) for SarA. EEE was the only ligand to exhibit a stable ligand-protein complex with SarA in the MD simulation of 200 ns (binding energy of MMPBSA analysis -39.899 kJ/mol). Chrysophanol, epicatechin and physcion, of C. fistula (-10.5, -10.5, and -11.0 kcal/mol, respectively) and auraptene of F. limonia (-10.8 kcal/mol) showed the best predictive binding affinity for LasR. Epicatechin showed the most stable ligand-protein complex with LasR (binding energy of MMPBSA analysis -63.717 kJ/mol).

Epicatechin and its derivative EEE could be used as scaffolds for the development of new antibiofilm agents against P. aeruginosa and S. aureus, respectively.

The aim of this study was to develop a clinical application model for the rational use of caffeine.

Caffeine is related to the incidence of neuro immune gastrointestinal diseases. Coffee consumption needs to be optimized in order to reduce the incidence rate.

By using KEEG analysis to explore potential molecular signaling pathways involved in the progression of neurological immune gastrointestinal diseases, and analyzing the details of this signaling Pathway using molecular simulation results, which can support AI system for doctor.

The research team designed a controlled experiment to analyze the differences in reward and reinforcement of Brain pleasure/addiction and dopamine related signaling pathways function between multiple groups of people with different coffee drinking habits and a blank control group. The study team used molecular dynamics methods to investigate the signaling route that links coffee with the binding of dopamine receptor D3.AI is used to predict the prevalence of gastric reflux disease.

Human experiments have shown a correlation between caffeine intake and gastroesophageal reflux disease. AI algorithm results can provide clinical support, and molecular simulation results are consistent with human experimental results. Caffeine and DRD3 protein have a stable interaction system.

The research team elucidated the intermolecular interaction between caffeine and DRD3, and AI algorithms can predict the likelihood of disease occurrence, providing a new strategy for clinical practice. This study has passed ethical approval at Chifeng Cancer Hospital, and the ethical documents for this study have been submitted to the World Health Organization for filing.

Gene therapy has been effectively applied in many biological studies and for the treatment of many genetic or cancer diseases. Currently Recombinant Adeno-Associated Viruses (rAAVs) are one of the main types of delivery vectors used for gene therapy. rAAV vectors produced via the Sf9 cells have the advantages of high rAAV yields easy scale-up and low cost.

Here we used Sf9 rhabdovirus-negative (Sf9-RVN) cells to validate and optimize the rAAV production process and the fed-batch process increased the rAAV production titre.

In the fed-batch procedure the cell density reached 12.9×106 cells/mL which was approximately twice as high as in the batch culture process. The rAAV titre was also approximately 8-fold higher in the fed-batch process reaching 1.5×10¹² VG/mL. The optimized process was validated by generating rAAVs with various serotypes and genes of interest (GOI) all of which gave production titres greater than 1×10¹² VG/mL.

We used Sf9-RVN cells to develop a fed-batch rAAV production process that replaces Sf9 cells to meet regulatory standards. This process has good applicability and the rAAV titre can reach at least 1×10¹² VG/mL which is higher than the level of 10¹¹ VG/mL reported in the literature.

Dilated Cardiomyopathy (DCM) is a debilitating cardiovascular disorder that challenges current therapeutic strategies. The exploration of novel drug repositioning opportunities through gene expression analysis offers a promising avenue for discovering effective treatments.

This study aims to identify potential drug repositioning opportunities and lead compounds for DCM treatment by optimizing gene expression characteristics using published data.

Our approach involved analyzing DCM expression profiles from the Gene Expression Omnibus database and identifying differentially expressed genes with GEO2R. A protein interaction network was constructed using the STRING database and visualized with Cytoscape. Enrichment analyses were conducted on these genes through the Omicshare platform, followed by the identification of candidate compounds via the Connectivity Map (CMAP) and validation through molecular docking. The Coremine Medical database was utilized to predict potential herbal medicines.

We identified 29 differentially expressed genes, highlighting MYH6, NPPA, and NPPB as central to DCM pathology. Enrichment analyses indicated significant impacts on biological processes, such as organ morphogenesis and inflammatory responses. The AGE-RAGE signaling pathway was notably affected. From over 6,100 compounds analyzed, tenoxicam emerged as a promising candidate, with Radix Salviae Miltiorrhizae (Danshen) being suggested as a potential herbal treatment.

This study underscores the utility of bioinformatics in uncovering new therapeutic candidates for DCM, offering a foundational step towards novel drug development.

Wound healing is a complex procedure frequently delayed in patients with underlying chronic conditions. Despite essential advances in tissue engineering and regenerative medicine, wound healing remains challenging, warranting novel methods for promoting wound healing. It has been demonstrated that exosomes are one of the main secretory products of different cell types, such as Mesenchymal Stem Cells (MSCs), for regulating various biological processes, including wound healing. Henceforth, understanding these exosome effects might assist in improving wound management and highlight a novel therapeutic model for cell-free therapies with reduced side effects for repairing wounds.

This systematic review involved conducting research electronically on scholarly scientific databases, including PubMed, Science Direct, and Scopus. Eligibility checks were performed based on predefined selection criteria. Finally, thirty-nine studies were considered.

Exosomes have been indicated to use multitargeted pathways to improve wound healing by modulating numerous dysregulated signaling cascades involved in cell proliferation, cell cycle regulation, metastasis, apoptosis, and angiogenesis.

The outcome of this review might guide pre-clinical and clinical studies on the role of exosomes in skin wound healing.

Combining immune checkpoint inhibitors and antiangiogenic agents offers a promising strategy to counteract the cooperative promotion of solid tumor growth by immune checkpoints and intratumoral angiogenesis.

We investigated the potential of thalidomide (THD) and anti-PD-1 antibody (PD-1 mAb) in suppressing tumor growth, enhancing immunity, and inhibiting angiogenesis.

THD exhibited regulatory effects on PD-1 in CD4⁺ T cells and PD-L1 in cancer cells, along with tumor growth inhibition in A549 and Lewis lung carcinoma (LLC) cell lines. Combined with PD-1 mAb, THD increased intracellular IL-2 and IFN-γ expression in CD4⁺ T cells, enhanced granzyme (Gzm-B) expression in peripheral blood mononuclear cells (PBMCs), and reduced TNF-α expression in CD4⁺ T cells. In C57BL/6 mice, THD plus PD-1 mAb decreased LLC-derived lung tumor weight and volume, boosted CD8⁺ T cell infiltration in tumors, and reduced CD34⁺ intratumoral microvessel density.

This study highlights THD’s role in modifying the tumor microenvironment to enhance PD-1 mAb efficacy, proposing a clinically feasible approach for improving PD-1 mAb treatment outcomes.

A stone is a compact mass of one or more crystallised substances. The essential mechanism of stone formation is an excessive concentration of poorly soluble compounds in the urine. In excessive concentration, these compounds precipitate into crystals, which then aggregate to form a stone. The use of certain plants using the turbidimetric model has shown positive results on oxalocalcic crystallisation and, according to a recent study, has revealed very high inhibition rates.

The aim of this study was to dissolve calcium oxalate urinary stones using two medicinal plants with high inhibition rates by monitoring Ca²⁺ release, pH variation, and mass loss. The study consisted of treating the stones with two plants, Ficus-carica and Zea mays, at two concentrations of 10g/l and 25g/l for 24 hours.

The main analytical techniques used in this study were as follows: Morphological analysis using a binocular magnifying glass, Fourier transform infrared spectroscopic method, and potentiometric method along with specific calcium electrode and an analytical balance. The study on the release of Ca²⁺ in the presence of the different herbal teas during 8 treatments of 3 to 4 hours was carried out on a series of 33 stones with the same chemical composition from several spontaneous expulsions of a 43-year-old male subject with lithiasis.

The results showed a very remarkable effect of the Ficus-carica plant on Ca²⁺ release, which recorded 156.98 ppm, while Zea mays gave 130.63 ppm.

The kinetics of Ca²⁺ release were monitored by a potentiometer using a Ca^2+-specific electrode. Zea mays at 10g/l showed a slightly positive effect on calculus dissolution compared to Ficus-carica.