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Infections caused by Gram‐negative bacteria present a significant risk to human health worldwide. Novel strategies are needed to deal with the challenge caused by drug‐resistant bacteria. Here, we report a new approach to combat infections by targeting iron‐binding proteins to suppress bacterial growth. We investigated the function of the conserved periplasmic binding protein FecB from Vibrio alginolyticus. FecB was known to play a crucial role in the bacterial growth and to relate with biofilm formation. We then solved the crystal structures and elucidated the binding mechanism of FecB with ferric ion chelated by citrate. The results indicated that FecB binds weakly to one citrate molecule and strongly to the Fe3+‐(citrate)2 complex. Based on these results, a structure‐based virtual screening approach was conducted against FecB to identify small molecules that block ferric citrate uptake. Further evaluations in vivo and in vitro demonstrated that salvianolic acid C significantly suppressed bacterial growth, indicating that targeting bacterial nutrient absorption is a promising strategy for identifying potential antibacterial drugs. [ABSTRACT FROM AUTHOR]

Global warming has increased the growth of pathogenic Vibrio bacteria, which can cause foodborne illnesses and death. Vibrio bacteria require iron for growth and survival. They utilize a ferric ion‐binding protein (FbpA) to bind and transport Fe3+ into the cell. FbpA from Vibrio metschnikovii (Vm) is a potential target for inhibiting its growth. Rosmarinic acid (RA) can block the binding of VmFbpA to Fe3+; however, the molecular mechanism of Fe3+ binding and RA inhibition to VmFbpA is unclear. In this study, we used x‐ray crystallography to determine the Fe3+‐binding mode of VmFbpA and the mechanism of RA inhibition. The structures revealed that in the Fe3+ bound form, Fe3+ was coordinated to VmFbpA by two Tyr residues, two HCO3− ions, and two water molecules in a six‐coordinated geometry. In contrast, in the inhibitor bound form, RA was initially bound to VmFbpA following gel filtration purification, but it was hydrolyzed to danshensu (DSS), which occupied the binding site as shown in an electron density map and reverse phase chromatography (RPC) analysis. Both RA and DSS exhibited a stronger binding affinity to VmFbpA, higher Fe3+ reduction capacity, and more potent bacteriostatic effect on V. metschnikovii compared with caffeic acid (CA), another hydrolysis product of RA. These results provide insight into the mechanism of iron acquisition by V. metschnikovii and inhibition by RA and DSS. Our findings offer clues on the development of effective strategies to prevent Vibrio infections. [ABSTRACT FROM AUTHOR]

Background and Aim: So far, the understanding of the role of Epstein-Barr virus-induced gene 3 (EBI3) in breast cancer has been limited. This study uncovers the functional role and clinical significance of EBI3 in breast cancer patients. Patients and Methods: The expression levels of EBI3, IL-27p28, and IL-12p35 were measured by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Correlations of EBI3 expression with IL-27p28 and IL-12p35 expression were analyzed using Pearson's correlation assay. The prognostic performance of EBI3 was assessed via Kaplan-Meier survival assay and Cox regression analysis. Results:EBI3 expression was increased in cancerous tissues compared with the controls (P < 0.05). This overexpression of EBI3 was correlated with lymph node metastasis and clinical stage (both P < 0.05). Besides, elevated expression of EBI3 was usually found in patients with positive lymph node metastasis (P < 0.05), and similar results were obtained in advanced clinical-stage breast cancer cases (P < 0.05). Increases in both IL-27p28 and IL-12p35 expression were identified in breast cancer tissues (all P < 0.05), and IL-12p35 expression was found to be associated with EBI3 expression (R = 0.888, P < 0.001). Survival curves revealed that high EBI3 expression was correlated with poor overall survival (log-rank P < 0.05). The Cox analysis indicated that EBI3 was an independent prognostic factor in breast cancer. Conclusion: Taken together, overexpression of EBI3 was associated with poor prognosis and might be involved in the progression of breast cancer. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study is to investigate whether hospital-based transitional care can reduce the postoperative complication in patients who received enterostomy or not by pooling the published prospective clinical studies.Materials and Methods: Prospective clinical studies related to hospital-based transitional care for reducing the postoperative complication in patients with enterostomy were searched in the electronic databases of PubMed, Medline, EMBASE, CNKI, and Wanfang. The postoperative complications in the experiment and control groups were extracted from the original studies and pooled by fixed effects model. The publication bias was evaluated by Begg's funnel plot and Egger's line regression test.Results: After searching through the electronic databases of PubMed, Medline, EMBASE, CNKI, and Wanfang, we finally included in eight studies with 600 cases related to hospital-based transitional care and postoperative complication in patients with enterostomy. The pooled result showed that hospital-based transitional care could significantly reduce the postoperative complication in patients with enterostomy (risk ratio = 0.42, 95% confidence interval: 1.0.32, ~0.55, P = 0.005) by fixed effects model. The Begg's funnel plot demonstrated a litter left-right asymmetry, which indicated potential publication bias. Moreover, Egger's line regression test showed that there were significant publications (t = -3.04, P = 0.023).Conclusion: Hospital-based transitional care can significantly reduce the postoperative complication in patients with enterostomy. [ABSTRACT FROM AUTHOR]

AbstractBackgroundObjectiveMethodsResultsConclusionNuclear Medicine(NM), as an inherently interdisciplinary field, integrates diverse scientific principles and advanced imaging techniques. The advent of ChatGPT, a large language model, opens new avenues for medical educational innovation. With its advanced natural language processing abilities and complex algorithms, ChatGPT holds the potential to substantially enrich medical education, particularly in NM.To investigate the current application of ChatGPT in undergraduate Nuclear Medicine Education(NME).Employing a mixed-methods sequential explanatory design, the research investigates the current status of NME, the use of ChatGPT and the attitude towards ChatGPT among teachers and students in the Second Clinical College of Chongqing Medical University.The investigation yields several salient findings: (1) Students and educators in NM face numerous challenges in the learning process; (2) ChatGPT is found to possess significant applicability and potential benefits in NME; (3) There is a pronounced inclination among respondents to adopt ChatGPT, with a keen interest in its diverse applications within the educational sphere.ChatGPT has been utilized to address the difficulties faced by undergraduates at Chongqing Medical University in NME, and has been applied in various aspects to assist learning. The findings of this survey may offer some insights into how ChatGPT can be integrated into practical medical education. [ABSTRACT FROM AUTHOR]

Global warming has increased the growth of pathogenic Vibrio bacteria, which can cause foodborne illnesses and death. Vibrio bacteria require iron for growth and survival. They utilize a ferric ion-binding protein (FbpA) to bind and transport Fe 3+ into the cell. FbpA from Vibrio metschnikovii (Vm) is a potential target for inhibiting its growth. Rosmarinic acid (RA) can block the binding of VmFbpA to Fe 3+ ; however, the molecular mechanism of Fe 3+ binding and RA inhibition to VmFbpA is unclear. In this study, we used x-ray crystallography to determine the Fe 3+ -binding mode of VmFbpA and the mechanism of RA inhibition. The structures revealed that in the Fe 3+ bound form, Fe 3+ was coordinated to VmFbpA by two Tyr residues, two HCO 3 - ions, and two water molecules in a six-coordinated geometry. In contrast, in the inhibitor bound form, RA was initially bound to VmFbpA following gel filtration purification, but it was hydrolyzed to danshensu (DSS), which occupied the binding site as shown in an electron density map and reverse phase chromatography (RPC) analysis. Both RA and DSS exhibited a stronger binding affinity to VmFbpA, higher Fe 3+ reduction capacity, and more potent bacteriostatic effect on V. metschnikovii compared with caffeic acid (CA), another hydrolysis product of RA. These results provide insight into the mechanism of iron acquisition by V. metschnikovii and inhibition by RA and DSS. Our findings offer clues on the development of effective strategies to prevent Vibrio infections., (© 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

The morphological changes from single-cell yeast to filamentous hypha form are critical in plant pathogenic smut fungi. This dimorphic switch is tightly regulated by complex gene pathways in pathogenic development. The phytopathogenic basidiomycetes Sporisorium scitamineum displays a morphological transition from budding growth of haploid cells to filamentous growth of the dikaryon, which enables fungi to forage for nutrients and evade the host plant immune system. In the search for compounds that affect dimorphic switch instead of killing the cell directly, a natural product, mycophenolic acid (MPA), was purified and exhibited significant dimorphism inhibitory activities with minimum effective concentrations of 0.3 μg/mL. RNA sequencing and real-time quantitative transcription-PCR analysis showed that treatment of 100 μg/mL MPA dramatically repressed the expression of the ammonium transporter gene Ssa2 . A further subcellular localization experiment, ammonium response assay, and Western blot assay confirmed that Ssa2 could be one of the most important molecular targets of MPA in regulating dimorphism of S. scitamineum. These observations suggest that Ssa2 serves as a molecular target of MPA and could be used in the treatment of sugar cane smut diseases caused by S. scitamineum.

The effects of a proprietary topical formulation containing EGCG-stearate in 100% glycerin USP were studied in two volunteer patients with recurrent herpes simplex (HSV) type 1. Application during early onset (prodromal stage) in a patient with herpes labialis prevented lesion progression. In a second patient with herpetic stomatitis, application of the formula during a later stage (inflammation stage) led to a remarkably shortened duration of symptoms. In contrast, a third patient provided 100% glycerin USP only as placebo failed to demonstrate any therapeutic or preventive effect against lesion occurrence or duration of lesion and healing time. These results suggest that this proprietary topical preparation could be used effectively to prevent and treat HSV-induced symptoms, and warrants further clinical investigation.

Multicellular resistance (MCR) is produced because multicellular spheroids (MCSs) are formed with a broad cell-cell connection when cultured in three-dimensions, which limits the clinical treatment efficacy in solid tumors. Focal adhesion kinase (FAK) plays an important role in apoptosis, survival and cell adhesion between cells and their extracellular matrix. In this study, we investigated the expressions of FAK, Akt and NF-kappaB in human colorectal cancer (CRC), and the effects of FAK gene silencing on MCSs formation and 5-fluorouracil (5-FU) chemosensitivity in colon carcinoma MCSs culture cells. In CRC samples, FAK, Akt and NF-kappaB were overexpressed. The positive expression of FAK correlated notably with lymph node metastasis and cellular differentiation. Positive expressions of Akt and NF-kappaB were significantly related to cellular differentiation and lymph node metastasis, respectively. Furthermore, positive expression of FAK correlated with that of Akt and NF-kappaB. The expression of FAK was inhibited significantly by a small hairpin RNA targeting FAK. Knockdown of FAK reversed the formation and aggregation of MCSs, significantly decreased the 50% inhibitory concentration of 5-FU, and markedly increased MCS culture cells apoptosis. These effects were associated with reduced levels of Akt and NF-kappaB. These results indicate that suppressing FAK expression potentiated 5-FU-induced cytotoxicity and contributed to its chemosensitizing effect by suppressing Akt/NF-kappaB signaling in colon carcinoma MCS culture cells. These data also imply that FAK mediates MCR of CRC through the survival signaling pathway FAK/Akt/NF-kappaB.