Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections.

Wound infection is one of the most important factors affecting wound healing, so its effective control is critical to promote the process of wound healing. However, with the increasing prevalence of multi-drug-resistant (MDR) bacterial strains, the prevention and treatment of wound infections are now more challenging, imposing heavy medical and financial burdens on patients. Furthermore, the diminishing effectiveness of conventional antimicrobials and the declining research on new antibiotics necessitate the urgent exploration of alternative treatments for wound infections. Recently, phage therapy has been revitalized as a promising strategy to address the challenges posed by bacterial infections in the era of antibiotic resistance. The use of phage therapy in treating infectious diseases has demonstrated positive results. This review provides an overview of the mechanisms, characteristics, and delivery methods of phage therapy for combating pathogenic bacteria. Then, we focus on the clinical application of various phage therapies in managing refractory wound infections, such as diabetic foot infections, as well as traumatic, surgical, and burn wound infections. Additionally, an analysis of the potential obstacles and challenges of phage therapy in clinical practice is presented, along with corresponding strategies for addressing these issues. This review serves to enhance our understanding of phage therapy and provides innovative avenues for addressing refractory infections in wound healing.

Increased Expression and Prognostic Significance of BYSL in Melanoma.

We evaluated the BYSL content and underlying mechanism in melanoma (SKCM) overall survival (OS). In this study, we used a comprehensive approach combining bioinformatics tools, including miRNA estimation, quantitative real-time polymerase chain reaction (qRT-PCR) of miRNAs, E3 ligase estimation, STRING analysis, TIMER analysis, examination of associated upstream modulators, protein-protein interaction (PPI) analysis, as well as retrospective and survival analyses, alongside clinical sample validation. These methods were used to investigate the content of BYSL, its methylation status, its relation to patient outcome, and its immunologic significance in tumors. Our findings revealed that BYSL expression is negatively regulated by BYSL methylation. Analysis of 468 cases of SKCM RNA sequencing samples demonstrated that enhanced BYSL expression was associated with higher tumor grade. We identified several miRNAs, namely hsa-miR-146b-3p, hsa-miR-342-3p, hsa-miR-511-5p, hsa-miR-3690, and hsa-miR-193a-5p, which showed a strong association with BYSL levels. Furthermore, we predicted the E3 ubiquitin ligase of BYSL and identified CBL, FBXW7, FZR1, KLHL3, and MARCH1 as potential modulators of BYSL. Through our investigation, we discovered that PNO1, RIOK2, TSR1, WDR3, and NOB1 proteins were strongly associated with BYSL expression. In addition, we found a close association between BYSL levels and certain immune cells, particularly dendritic cells (DCs). Notably, we observed a significant negative correlation between miR-146b-3p and BYSL mRNA expression in SKCM sera samples. Collectively, based on the previously shown evidences, BYSL can serve as a robust bioindicator of SKCM patient prognosis, and it potentially contributes to immune cell invasion in SKCM.

Gooderoside A from Anoectochilus elatus attenuates acute and chronic pains by inhibiting NO/cGMP and IRAK4/IRAK1/TAK1 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus elatus Lindl. was traditionally used for pain treatment and Gooderoside A (GA) was regarded as its principal constituent. AIM OF THE STUDY: To investigate whether GA can be responsible for the antinociceptive activity of A. elatus and explore its underlying mechanism. MATERIALS AND METHODS: Acetic acid-induced abdominal writhing and tail flick tests were employed to evaluate the antinociceptive activity of ethanolic extract of A. elatus (EEA) and GA. Formalin test was used to ascertain the antinociceptive pattern of GA. Entobarbital sodium induced sleep test was adopted to exclude its hypnotic effect, while open-field test was performed to rule out its motor impairment effect. Chronic constriction injury (CCI)-induced neuropathic pain in rats was developed to evaluate its efficacy on neuropathic pain, and BV-2 cells were used to explore the underlying mechanism. RESULTS: EEA and GA, significantly inhibited chemical and thermal nociception. GA suppressed nociception in formalin test in both phase I and II, whereas methylene blue and L-NAME partially reversed its efficacy. GA located inner and slightly blocked sodium channel current, and did not show any hypnotic effect or motor impairment effect. Crucially, GA markedly attenuated chronic neuropathic pain in rats, inhibited the phosphorylation of IRAK4, IRAK1 and TAK1, and suppressed MAPKs pathway in BV-2 cells. CONCLUSION: GA relieved acute and chronic pains in vivo. The mechanism of action involves the blocking of NO/cGMP and IRAK4/IRAK1/TAK1 pathways. These results suggested GA may be a promising candidate for antinociceptive drug development.

Interdigital-type antifungal socks for prevention and treatment of tinea pedis.

BACKGROUND: Interdigital tinea pedis is the most common type of foot infection, which is often treated by topical or systemic antifungals. Due to the increase in antifungal resistance, antifungal socks are becoming potential alternatives for the daily management of tinea pedis. METHODS: In this study, antifungal fibres were adopted to produce interdigital hygiene socks to split the third and fourth toe seams of the feet. In vitro antifungal activity was first examined to verify the effectiveness of the socks. Preventive efficacy against tinea pedis was then evaluated among healthy participants, followed by therapeutic effect detection in patients diagnosed with tinea pedis by analysing the improvement in total symptom scores (TTS). RESULTS: The interdigital-type hygiene socks exhibited apparent antifungal activities in vitro. An in vivo study demonstrated significant preventive effects against tinea pedis for interdigital socks compared to plain socks (P = 0.011) and a lower TTS than noninterdigital (P = 0.04) or plain socks (P < 0.0001). Moreover, interdigital socks showed a total effectiveness rate of 72.9% in patients with tinea pedis, with most of the symptoms alleviated. CONCLUSION: Interdigital-type hygiene socks not only exhibited in vitro antifungal activities but also showed significant prophylactic and therapeutic effects against interdigital tinea pedis in vivo.