Invasive candidiasis is a major threat to human health, and Candida albicans is the most common pathogenic species responsible for this condition. The incidence of drug-resistant strains of C. albicans is rising, necessitating the development of new antifungal drugs. Antimicrobial peptides (AMPs) have recently attracted attention due to their unique ability to evade the drug resistance of microorganisms. However, the mechanism of their activity has not yet been identified. The current study analyzed the mode of action of MAF-1A by confocal microscopy, scanning electron microscopy, fluorescent staining, flow cytometry, and qRT-PCR. The results indicate that MAF-1A disrupts the cell membrane of C. albicans and enters the cell where it binds and interacts with nucleic acids. qRT-PCR demonstrated that the expression of several sterol biosynthesis–related genes in C. albicans was increased after MAF-1A treatment. Together, these findings suggest that MAF-1A exerts antifungal action by affecting both the cell membrane and intracellular components. The antifungal mechanism of MAF-1A is unique, and its identification has great research and clinical significance.

To investigate the ameliorated effects of an extract of Ginkgo biloba extract (GBE) on experimental cardiac remodeling in rats induced by acute cardiac infarction, and further explore the mechanism concentrated on myocardial type I collagen, transforming growth factor beta 1 (TGF-β1), matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and provide the experimentaldata for clinical application of GBE. Rats were divided into five groups (n = 20) as following: sham operation group (group A), acute myocardial infarction model group (group B), acute myocardial infarction model + aspirin (10 mg/kg) treatment group (group C), acute myocardial infarction model + captopril (20 mg/kg) treatment group (group D) and acute myocardial infarction model + Ginkgo biloba extract (100 mg/kg) treatment group (group E). The rat acute myocardial infarction model was reproduced by ligaturing the left anterior descending artery excluding the sham operation group which did not ligation only completed the operational process. Each group was further subdivided into treatment regimens lasting 4 weeks and 8 weeks. Immunohistochemistry and real-time polymerase chain reaction (PCR) methods were used to detect the protein expression and mRNA transcriptional levels of rat myocardial TGF-β1, type I collagen, MMP-2 and MMP-9. Compared with group B, regardless of the length of treatment (4 or 8 weeks), the TGF-β1, MMP-2 and MMP-9 mRNA transcriptional levels, and the protein expression levels of type I collagen, MMP-2 and MMP-9 in groups D, C and E were significantly decreased (P < 0.01). Furthermore, the mRNA expression levels of TGF-β1 in groups D, C and E were significantly lower after 8 weeks compared to after 4 weeks (P < 0.01), as were the expression levels of type I collagen in groups D, C and E (P < 0.05). There was no statistically significant difference in the protein expression levels of MMP-2 and MMP-9 between groups E and C. GBE could inhibit experimental rat myocardial remodeling after acute myocardial infarction via reduced transcription of TGF-β1, MMP-2 and MMP-9 genes and by the decreased expression of type I collagen, MMP-2 and MMP-9 proteins in myocardial cells.

Background: Soluble lymphocyte activation gene 3 (sLAG3) may be used for diagnosis or prognosis in various diseases. However, the relationship between sLAG3 and coronary artery disease (CAD) are still unclear. This study aimed to investigate the levels of sLAG3 in patients with CAD, and its potential clinical association with the disease.Methods: A total of 66 subjects (49 patients with CAD and 17 control subjects without CAD) were enrolled. The sLAG3 level was measured using enzyme-linked immunosorbent assay (ELISA) kits. Clinical variables included demographics, biochemical markers, coronary angiography status, and ejection fraction of the heart (EF) were collected, and Gensini scores were calculated. LAG3 gene data was extracted from three datasets (GSE23561, GSE61144, GSE60993) in Gene Expression Omnibus (GEO) to compare differential expression between CAD and control subjects.Results: The sLAG3 level was significantly lower in the CAD vs. the controls (P < 0.05), and negatively associated with CAD [odds ratio (OR): 0.212, 95% confidential interval (CI): 0.060–0.746, P < 0.05]. Furthermore, the area under the curve (AUC) of sLAG3 level was significant (P < 0.05). The sLAG3 level in subjects with body mass index (BMI) ≥ 24 kg/m² was lower compared to those with BMI < 24 kg/m² (P < 0.05). The sLAG3 level was also negatively associated with BMI and diabetes mellitus (P < 0.05), though not associated with the Gensini scores or EF (P > 0.05). Lastly, the LAG3 gene expression in peripheral whole blood of patients with CAD were down-regulated compared to healthy controls (P < 0.05).Conclusion: The sLAG3 level was negatively associated with the occurrence but not severity of CAD. Meanwhile, the sLAG3 was negatively associated with BMI and diabetes mellitus, suggesting the reduced sLAG3 might be a novel risk factor for developing CAD.

Candida parapsilosis is a major fungal pathogen that leads to sepsis. New and more effective antifungal agents are required due to the emergence of resistant fungal strains. MAF-1A is a cationic antifungal peptide isolated from Musca domestica that is effective against a variety of Candida species. However, the mechanism(s) of its antifungal activity remains undefined. Here, we used RNA-seq to identify differentially expressed genes (DEGs) in Candida parapsilosis following MAF-1A exposure. The early (6 h) response included 1,122 upregulated and 1,065 downregulated genes. Late (18 h) responses were associated with the increased expression of 101 genes and the decreased expression of 151 genes. Upon MAF-1A treatment for 18 h, 42 genes were upregulated and 25 genes were downregulated. KEGG enrichment showed that the DEGs in response to MAF-1A were mainly involved in amino acid synthesis and metabolism, oxidative phosphorylation, sterol synthesis, and apoptosis. These results indicate that MAF-1A exerts antifungal activity through interference with Candida parapsilosis cell membrane integrity and organelle function. This provides new insight into the interaction between Candida parapsilosis and this antimicrobial peptide and serves as a reference for future Candida parapsilosis therapies.