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Developing natural alternatives to antibiotics is an essential aspect for countering bacterial pathogens. This study focused on the influence of plant-derived extracts on biofilm and quorum-sensing (QS) inhibition in Pseudomonas aeruginosa. On screening, the methanolic extract (ME) of Sapindus mukorossi (Sm-ME) effectively inhibited biofilm formation. The major bioactive groups present in Sm-ME were alkaloids, flavonoids, terpenoids, and saponins. These phytochemicals were validated by biochemical, Fourier transform infrared spectroscopy, and gas chromatography-mass spectroscopy analysis. Sm-ME significantly inhibits up to 82.5% of P. aeruginosa biofilm formation and anti-QS activity in a dose-dependent manner. The microscopy analysis and the down-regulation of virulence genes (lasI, lasR, rhII, and rhIIR) validated the effectiveness of Sm-ME in P. aeruginosa inhibition. Additionally, Sm-ME retained good biocatalytic activity on exposure to high temperatures up to 90°C and higher antioxidant activity than ascorbic acid. These findings briefly demonstrated the potential influence of Sm-ME for combating biofilm and QS inhibitions in P. aeruginosa via a natural, sustainable alternative to antibiotics.

Significant heterogeneity in the immune microenvironment of Glioblastoma, IDH-wildtype (GBM), has been reported, necessitating a standardized approach to evaluate immune infiltration in the context of emerging immunotherapies. To address this, we developed and validated a standardized immunohistochemistry-based scoring system for quantifying immune cell infiltration in formalin-fixed, paraffin-embedded (FFPE) tissue. Paired primary and recurrent GBM specimens from 20 adult patients were labeled for CD3, CD8, CD45, CD68, and PD-1, and scored across six anatomical regions, including intra- and peritumoral, meningeal, and normal brain areas. The scoring system demonstrated excellent interrater (ICC = 0.932) and intrarater (ICC = 0.953) reliability. CD68+ and CD45+ cells were most numerous across all regions. CD3+ and CD8+ cells concentrated more in the perivascular area rather than within the parenchyma. No significant differences in immune infiltration were observed between primary and recurrent GBM. Cox proportional-hazards analysis showed worse survival with higher CD8+ and CD45+ infiltration in primary GBM, and higher CD45+ and CD68+ infiltration in recurrent GBM. In conclusion, we propose a feasible, cost-efficient, and robust method to assess immune infiltration on FFPE material, enabling standardized comparison of inflammation, with applications for ongoing clinical trials.

This study aimed to investigate the role of YTHDF1, a key m6A reader protein, in ulcerative colitis (UC) pathogenesis and its potential involvement in ferroptosis through ACSL4 regulation. Clinical serum and tissue samples from UC patients, as well as dextran sulfate sodium (DSS)- and oxazolone (OXZ)-induced colitis mouse models, were used to assess YTHDF1 expression and its correlation with disease severity. Ferroptosis markers, including reactive oxygen species (ROS), lipid peroxidation products, and iron levels, were assessed in both colonic tissues and DSS-treated Caco-2 cells. RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays were performed to explore YTHDF1-mediated mRNA stabilization of ACSL4. Data showed that YTHDF1 was significantly upregulated in the serum and colonic tissues of UC patients, with expression levels correlating positively with disease severity. In UC mouse models, YTHDF1 expression was increased, and its knockdown reduced colitis severity. Mechanistically, YTHDF1 knockdown suppressed ferroptosis by reducing lipid peroxidation, ROS accumulation, and iron overload. Additionally, ACSL4, a key ferroptosis regulator, was identified as a downstream target of YTHDF1, with YTHDF1 stabilizing ACSL4 mRNA through m6A modifications. Collectively, YTHDF1 promotes ferroptosis in UC by stabilizing ACSL4 mRNA through m6A modifications and highlights its potential as a therapeutic target for UC treatment.

Prostate cancer is the most common malignancy among men worldwide, and treatment response depends on tumor radiosensitivity. Micrornas (mirnas) are key regulators of cell proliferation, apoptosis, and dna damage response, and have been implicated in therapy resistance. However, their roles in prostate cancer radioresponse remain incompletely understood. This study investigated the expression patterns of ten selected mirnas associated with radiation resistance in other cancers in prostate cancer models. Radiation-resistant pc-3, radiation-sensitive lncap, and normal prostate epithelial (hprec) cells were exposed to 0, 2, 4, 6, and 8 gy of ionizing radiation. Mirna expression levels were analyzed by quantitative pcr using snord48 as an internal control and calculated with the 2 - δδct method. In pc-3 cells, mir-20a-5p, mir-128-3p, and mir-135b-5p showed significant dose-dependent upregulation, whereas mir-23b-3p and mir-381-3p were downregulated. Mir-128-3p correlated positively with radiation dose, while mir-23b-3p and mir-381-3p showed negative correlations. Lncap cells exhibited moderate, non-dose-dependent mirna changes. Distinct mirna signatures differentiate radiation-resistant and radiation-sensitive prostate cancer cells. Mir-20a-5p, mir-128-3p, and mir-135b-5p may contribute to radioresistance, whereas mir-23b-3p and mir-381-3p may act as radiosensitizers.

Interkingdom polymicrobial biofilms of Staphylococcus aureus and Candida albicans increase pathogenicity and complicate treatment strategies, contributing to greater morbidity and mortality. These infections are typically investigated using the C. albicans strain SC5314, despite its uncertain clinical relevance. Here, we evaluate how different C. albicans (high, intermediate, low biofilm formers) and S. aureus strains influence biofilm tolerance to both conventional antimicrobials and cold atmospheric plasma (CAP). CAP is an emerging technology that has been shown, including in our prior work, to disrupt biofilm biomass via reactive oxygen and nitrogen species, positioning it as a promising adjunct to antimicrobial therapy. We determined how strain variation influenced biofilm structure and tolerance to vancomycin, amphotericin B and CAP. Interkingdom biofilm architecture was primarily influenced by the C. albicans strain, particularly its ability to form hyphae. Despite this, all strains conferred protection to S. aureus against vancomycin. CAP eradicated S. aureus biofilms within 120 s, but this effect was lost in dual-species biofilms. However, CAP pretreatment enhanced the efficacy of both antimicrobials in interkingdom biofilms. These findings highlight the role of hyphal morphology in vancomycin tolerance and support further clinical evaluation of CAP as a biofilm-targeting adjunct.

Blood stream infections are associated with high mortality and morbidity. NEWS2 is a quick scoring system including bedside measurable vital signs. This study aimed to investigate the ability of NEWS2 ≥ 5p to identify sepsis, per Sepsis-3 criteria, among adult patients with community-acquired infection and positive blood cultures. It also explored if NEWS2 ≥ 5p could indicate infection etiology based on bacterial species in blood culture. This retrospective study included 555 patients with positive blood cultures. 425 of 555 (76.6%) patients had sepsis. The sensitivity of NEWS2 ≥ 5p for detecting sepsis was 86.6% and was not statistically associated with infection etiology. Patients with S. pneumoniae had a higher median NEWS2 score than those with other bacterial species. The 28-day mortality rate was 12.1%, and the sensitivity of NEWS2 ≥ 5p for detecting 28-day mortality was 91.0%. NEWS2 ≥ 5p was detected in a high proportion of sepsis cases among patients with blood stream infections, independent of bacterial species, and is a quick tool for identifying high sepsis likelihood in the emergency department.