Exploring key genes associated with non-small cell lung carcinoma (NSCLC) may lead to targeted therapies for NSCLC patients. The protein kinase MAP4K3 has been established as an important modulator of cell growth and autophagy in mammals. Herein, we investigated the somatic mutations and the expression pattern of MAP4K3 detected in NSCLC patients based on the TCGA database. Abnormal MAP4K3 expression and its somatic mutations are associated with the carcinogenesis and thereby becoming an attractive therapeutic target. Baicalein, a natural product, was determined to be the first-reported MAP4K3 binding ligand with its KD values of 6.47 μM measured by microscale thermophoresis. Subsequent in silico docking and mutation studies demonstrated that baicalein directly binds to MAP4K3, presumably to the substrate-binding pocket of this kinase domain, causing inactivity of MAP4K3. We further showed that baicalein could induce degradation of MAP4K3 through decreasing its stability and promoting the ubiquitin proteasome pathway. Degradation of MAP4K3 could cause dissociation of the transcription factor EB and 14-3-3 complex, enhance rapid transport of TFEB to the nucleus and trigger TFEB-dependent autophagy, resulting in lung cancer cells proliferation arrest. Knockdown of MAP4K3 expression by siRNA was sufficient to mimic baicalein-induced autophagy. Ectopic expression of the MAP4K3 protein resulted in significant resistance to baicalein-induced autophagy. Baicalein exhibited good tumor growth inhibition in a nude mouse model for human H1299 xenografts, which might be tightly related to its binding to MAP4K3 and degradation of MAP4K3. Our data provide novel mechanistic insights of baicalein/ MAP4K3/ mTORC1/ TFEB axis in regulating baicalein-induced autophagy in NSCLC, suggesting potential therapies for treatment of NSCLC.
This paper reviewed the diversity of endophytic fungi and their interactions with medicinal plants, along with the research methodologies utilized to investigate these interactions. It mainly includes the diversity of endophytic fungi, as well as distribution diversity, species diversity, and the diversity of their metabolites and functions, including antibacterial, anti-inflammatory, anti-tumor, insecticidal, antioxidant capabilities, and so on. The research methodologies employed to investigate the interactions between endophytic fungi and medicinal plants are categorized into metagenomics, transcriptomics, metatranscriptomics, proteomics, and metabolomics. Furthermore, this study anticipates the potential applications of secondary metabolites derived from endophytic fungi in both medicine and agriculture.
27 June 2023 in Frontiers in Bioengineering and Biotechnology
As nanotechnology develops in the fields of mechanical engineering, electrical engineering, information and communication, and medical care, it has shown great promises. In recent years, medical nanorobots have made significant progress in terms of the selection of materials, fabrication methods, driving force sources, and clinical applications, such as nanomedicine. It involves bypassing biological tissues and delivering drugs directly to lesions and target cells using nanorobots, thus increasing concentration. It has also proved useful for monitoring disease progression, complementary diagnosis, and minimally invasive surgery. Also, we examine the development of nanomedicine and its applications in medicine, focusing on the use of nanomedicine in the treatment of various major diseases, including how they are generalized and how they are modified. The purpose of this review is to provide a summary and discussion of current research for the future development in nanomedicine.
Cinnamon essential oil (CEO), a safe, medicinal, and edible Traditional Chinese Medicine (TCM) component, was investigated for its anti-Candida albicans property and ability to relieve intestinal inflammation. The anti-Candida albicans ability of CEO was evaluated by Minimum Inhibitory Concentration (MIC), 2,3-Bis-(2-Methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), and Scanning Electron Microscope (SEM) methods. By constructing ulcerative colitis (UC) mice intestinally colonized by C. albicans, the CEO effects on the regulation of flora, the relief of intestinal inflammation, and possible related signal pathway were discussed. The results showed that CEO has a significant effect on inhibiting C. albicans, where the MIC80 value was 265 μg/mL, and the Sessile Minimum Inhibitory Concentration (SMIC)80 value was 530 μg/mL. SEM showed the CEO could inhibit C. albicans mycelium growth and biofilm formation. CEO can regulate the flora disturbance, reduce inflammatory factors level, and play a protective role in intestinal mucosal damage. Network pharmacology predicts CEO may be associated with Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway. It was proved that CEO had an inhibitory effect on the JAK-STAT pathway by qPCR determination. These findings suggest CEO may have therapeutic potential for C. albicans–associated UC.
This article investigates the antifungal activity of clove essential oil (CEO) against Candida albicans, as well as its inhibitory effects on C. albicans biofilm formation and the associated developmental processes. Furthermore, it evaluates the therapeutic efficacy of CEO in a mouse model of intestinal C. albicans infection and explores its impact on intestinal microbiota. Additionally, 16S rRNA high-throughput sequencing was conducted to analyze the alterations in the intestinal microbiota. The findings indicate that the administration of CEO in mice infected with C. albicans resulted in a normalization of body weight and an improvement in their symptoms. Histological analysis utilizing HE and PAS staining demonstrated that CEO exerted beneficial effects on the intestinal mucosal status of these infected mice. Furthermore, ELISA results revealed a dose-dependent reduction in the levels of IL-6, IL-8, and IL-17A within the small intestinal tissues of C. albicans-infected mice. Additionally, 16S rRNA gene analysis indicated that CEO effectively enhanced the richness and diversity within the intestinal microbiota of CEO treatment groups of mice that were investigated. Overall, CEO exhibits therapeutic potential against inflammation induced by intestinal C. albicans infection in mice. This effect can be attributed to its anti-inflammatory properties as well as its capacity to regulate the composition of intestinal flora.