METHODS: To determine the antibacterial effectiveness of the MAC against Pseudomonas aeruginosa, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques were employed to observe bacterial morphology and biofilm formation. We further performed a biofilm inhibition assay to assess the effect of the MAC on biofilm formation. Whole-transcriptome sequencing and bioinformatics analysis were employed to elucidate the antibacterial mechanism of the MAC. Additionally, the expression levels of differentially expressed genes were validated using the real-time PCR approach.
RESULTS: Our findings demonstrated the antibacterial activity of the MAC against P. aeruginosa. SEM analysis revealed that the MAC can induce morphological changes in bacterial cells. The biofilm assay showed that the MAC could reduce biofilm formation. Whole-transcriptome analysis revealed 1093 differentially expressed genes consisting of 659 upregulated genes and 434 downregulated genes, in response to the MAC treatment. Mechanistically, the MAC inhibited P. aeruginosa growth by targeting metabolic processes, secretion system, signal transduction, and cell membrane functions, thereby potentially compromising the survival of this human pathogen. This study provides valuable insights into the antibacterial and antibiofilm activities of the MAC, a synergistic and cost-effective malic acid combination, which holds promise as a potential therapeutic drug cocktail for treating human infectious diseases in the future.
METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-455-5p expression in breast cancer tissues and cell lines. CCK8 and Transwell assays were conducted to assess the effects of miR-455-5p on breast cancer line proliferation, migration, and invasion. SOCS3 expression level in breast cancer tissues and cell lines was determined by qPCR and western blotting. The targeting relationship between miR-455-5p and SOCS3 was determined by dual luciferase reporter gene assay in different breast cancer cell lines. Finally, the upstream and downstream regulatory association between miR-455-5p and SOCS3 was confirmed in breast cancer cells by CCK8, western blot, and Transwell assays.
RESULTS: MiR-455-5p expression was up-regulated in breast cancer tissues; miR-455-5p regulates TNBC proliferation, migration, and invasion of TNBC. SOCS3 was the direct target of miR-455-5p and was down-regulated in breast cancer. Interference with SOCS3 reversed the inhibitory effect of the miR-455-5p inhibitor on breast cancer cells' malignant potential.
CONCLUSION: MiR-455-5p promotes breast cancer progression by targeting the SOCS3 pathway and may be a potential therapeutic target for breast cancer.
AIM OF THE STUDY: A more comprehensive and in-depth review about the geographical distribution, traditional uses, chemical constituents and pharmacological activities as well as safe and toxicity of Gynura species has been summarized, hoping to provide a scientific basis for rational development and utilization as well as to foster further research of these important medicinal plant resources in the future.
MATERIALS AND METHODS: A review of the literature was performed based on the existing peer-reviewed researches by consulting scientific databases including Web of Science, PubMed, Elsevier, Google Scholar, SciFinder and China National Knowledge Infrastructure.
RESULTS: Many of the Gynura species have been phytochemically studied, which led to the isolation of more than 338 compounds including phenolics, flavonoids, alkaloids, terpenoids, steroids, cerebrosides, aliphatics and other compounds. Pharmacological studies in vitro and in vivo have also confirmed the various bioactive potentials of extracts or pure compounds from many Gynura plants, based on their claimed ethnomedicinal and anecdotal uses, including antioxidant, anti-inflammation, anticancer, antidiabetic, antihypertension, antibacterial and other activities. However, pyrrolizidine alkaloids (PAs) pose a threat to the medication safety and edible security of Gynura plants because of toxicity issues, requiring the need to pay great attention to this phenomenon.
CONCLUSION: The traditional uses, phytochemistry and pharmacology of Gynura species described in this review demonstrated that these plants contain a great number of active constituents and display a diversity of pharmacological activities. However, the mechanism of action, structure-activity relationship, potential synergistic effects and pharmacokinetics of these components need to be further elucidated. Moreover, further detailed research is urgently needed to explain the mechanisms of toxicity induced by PAs. In this respect, effective detoxification strategies need to be worked out, so as to support the safe and reasonable utilization of Gynura plant resources in the future.