Fen Yao

Saxifraga stolonifera Meeb is widely used as a traditional Chinese medicine for the treatment of infections. This study aims to evaluate the antibacterial properties and suppression of virulence by Saxifraga stolonifera Meeb extracts on Pseudomonas aeruginosa . Following extraction of Saxifraga stolonifera Meeb with petroleum ether, ethyl acetate, n-butyl alcohol, and water, the n-butyl alcohol extract had the strongest activity against P. aeruginosa PAO1 and P. aeruginosa ATCC27853, with minimum inhibitory concentration (MIC) values of 10 and 5 mg/mL, respectively. In the presence of the n-butyl alcohol (n-BuOH) extract at 1/4MIC, genes lasI, lasR, rhlI, phzA1, phzA2, and pilG were decreased to levels ranging from 13% ( lasI ) to 43% ( phzA2 ). Both biofilm formation and pyocyanin production of PAO1 were inhibited by the n-BuOH extract at sub-inhibitory concentrations. N-butyl alcohol extract analyzed by HPLC-Q-TOF-MS/MS showed more than 11 compounds. Overall, our results suggest that the n-BuOH extract from Saxifraga stolonifera Meeb may be used as a new anti-virulence agent for P. aeruginosa infection. IMPORTANCE: Pseudomonas aeruginosa infections pose severe challenges to clinical treatment, and anti-virulence therapy has emerged as a novel therapeutic strategy. This study demonstrates that the n-butanol extract of Saxifraga stolonifera exerts anti-virulence effects by downregulating virulence-related genes, inhibiting quorum-sensing systems, and biofilm formation. Moreover, its multiple bioactive components also possess antibacterial and anti-virulence properties. S. stolonifera is thus promising to be developed into a novel anti-virulence inhibitor against P. aeruginosa for the prevention and treatment of clinically relevant infections.

Extracellular vesicles (EVs) are promising cell-free therapeutics for diabetic wound healing due to their immunomodulatory and proangiogenic properties. Nonetheless, challenges in ensuring long-term stability and achieving targeted delivery continue to impede clinical translation. Herein, we developed a 3-dimensional bioprinted methacrylated decellularized umbilical cord matrix (MDUM) patch enabling the sustained delivery of telomerase-immortalized umbilical cord mesenchymal stem cell-derived EVs (TMSC-EVs). TMSC-EVs encapsulated in MDUM maintained their structural integrity and biological functionality for more than 30 d under 4 °C storage, outperforming those encapsulated in gelatin methacryloyl ( P < 0.01). In a diabetic murine wound model, our data demonstrated that MDUM could enhance the retention and delivery of TMSC-EVs and further augment the therapeutic effects for diabetic wound healing as revealed by attenuating proinflammatory cytokine levels, enhancing neovascularization, and accelerating collagen deposition. This study pioneers the integration of biomaterial engineering with immortalized cell-derived EVs, establishing a translatable platform for regenerative therapies in chronic wound management.

Rationale: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and persistent inflammation in multiple joints is an important sign for the progression of RA. To this end, we developed the transdermal microneedle integrating biomimetic self-enhancing Fenton reaction nano-reactor, for the purposes of eliminating reactive oxygen species, reducing hypoxia and inflammation, and regulating macrophage phenotype.

This study aimed to investigate the high-resolution phenotypic and genotypic characterization of extended-spectrum β-lactamase (ESBL)-producing E. coli strains isolated from hospitalized patients to explore the resistance genes and mobile genetic elements (MGEs) involved in horizontal dissemination. Between May and September 2021, a total of 216 ESBL-producing E. coli isolates were recovered from multiple departments. The identification of strains was performed using MALDI-TOF mass spectrometry and PCR, while antibiotic susceptibility testing was carried out using the Vitek 2 COMPACT system to determine resistance patterns, while PCR was used to detect different resistance genes and MGEs. In addition, a conjugation assay was performed to investigate the horizontal gene transfer of resistance genes. Selected isolates underwent whole-genome sequencing using the Illumina MiSeq platform. A total of 216 out of 409 E. coli isolates recovered from a tertiary hospital were observed to be ESBL-producing, giving a carriage rate of 52.8%, as determined by phenotypic screening. The most frequent sources of ESBL-producing E. coli isolates were urine (129/216, 59.72%,) and blood (50/216, 23.14%). The most prevalent ESBL genes identified were bla_CTX-M (60.18%), bla_TEM (40.27%), and bla_SHV (18.05%). Three E. coli isolates were found to carry the genes bla_NDM, mcr-1, and fosA3 genes. The most prevalent MGEs were IS26 (95.37%), Int (87.03%), and IncFIB (76.85%). Whole-genome sequencing analysis of eight MDR E. coli strains revealed that these isolates belonged to eight different sequence types (STs) and serotypes and were found to harbor multiple plasmid replicons and virulence factors. This study highlights a high incidence of antibiotic resistance genes and MGEs associated with the dissemination of ESBLs and other resistance genes.

Linezolid has been reported to restore erythromycin susceptibility in erythromycin-resistant Staphylococcus aureus . This phenomenon has not been reported in enterococci and the mechanisms involved therein are still unknown. The purpose of this study was to investigate the mechanisms involved and the effect of combining linezolid with erythromycin on erythromycin-resistant enterococci . Checkerboard techniques were used to determine drug interactions, and 12 of 14 isolates showed a synergistic effect between erythromycin and linezolid (fractional inhibitory concentration erm (B) gene, which encodes a dimethyltransferase responsible for erythromycin resistance, was expressed from transposon Tn1545 in the tested erythromycin-resistant enterococci . After exposure to linezolid, erm (B)-mediated rRNA dimethylation at A2071 could not be detected, and the erm (B) gene was lost following acquisition of erythromycin susceptibility. Thus, in conclusion, linezolid combined with erythromycin exerts a synergistic effect against erythromycin-resistant enterococci . Linezolid treatment suppressed erm (B)-mediated rRNA dimethylation at A2071, which could lead to loss of the erm (B) gene.

Before the emergence of plasmid-mediated colistin resistance, colistin was once considered the last drug of choice for infections caused by carbapenem-resistant bacteria. Currently, researchers are relentlessly exploring possible alternative therapies that could efficiently curb the spread of drug resistance. In this study, we aim to investigate the synergistic antibacterial activity of tetrandrine in combination with colistin against mcr-1-harboring Escherichia coli. We examined the antibacterial activity of tetrandrine in combination with colistin in vivo and in vitro and examined the bacterial cells by fluorescence, scanning, and transmission electron microscopy (TEM) to explore their underlying mechanism of action. We further performed a computational analysis of MCR-1 protein and tetrandrine to determine the interaction interface of these two molecules. We confirmed that neither colistin nor tetrandrine could, on their own, inhibit the growth of mcr-1-positive E. coli. However, in combination, tetrandrine synergistically enhanced colistin activity to inhibit the growth of E. coli both in vivo and in vitro. Similarly, molecular docking showed that tetrandrine interacted with the three crucial amino acids of the MCR-1 protein in the active site, which might inhibit MCR-1 from binding to its substrates, cause MCR-1 to lose its ability to confer resistance. This study confirmed that tetrandrine and colistin have the ability to synergistically overcome the issue of colistin resistance in mcr-1-harboring E. coli.

Glycyrrhetic acid (GA)-modified pullulan nanoparticles (GAP NPs) were synthesized as a novel carrier of curcumin (CUR) with a degree of substitution (DS) of GA moieties within the range of 1.2–6.2 groups per hundred glucose units. In the present study, we investigated the physicochemical characteristics, release behavior, in vitro cytotoxicity and cellular uptake of the particles. Self-assembled GAP NPs with spherical shapes could readily improve the water solubility and stability of CUR. The CUR release was sustained and pH-dependent. The cellular uptake of CUR-GAP NPs was confirmed by green fluorescence in the cells. An MTT study showed CUR-GAP NPs with higher cytotoxicity in HepG2 cells than free CUR, but GAP NPs had no significant cytotoxicity. GAP is thus an excellent carrier for the solubilization, stabilization, and controlled delivery of CUR.