Relationships among gut microbes, the interleukin family, and hypertension: a mediation Mendelian randomization study.

Purpose: Observational studies have increasingly recognized the influence of gut microbes on blood pressure modulation. Despite these findings, a direct causal link between gut flora and hypertension remains unestablished due to inherent confounders and the challenges of reverse causality in observational research. In this study, we sought to elucidate the causal relationship between specific gut flora and hypertension and its intermediary mediators. Methods: We employed a two-sample Mendelian randomization (MR) and mediation MR analysis, analyzing 211 species of gut bacteria, with a focus on the interleukin family as potential mediators and hypertension as the primary outcome. The central methodological technique was inverse variance-weighted estimation, supplemented by various other estimators. Results: Our findings revealed that two bacterial species positively correlated with hypertension risk, while five exhibited a negative association. Further validation was conducted using sensitivity analyses. Notably, our mediation MR results suggest interleukin-1 receptor type 2 (IL-1R2) as a mediator for the effect of the genus Clostridium innocuum group on hypertension, accounting for a mediation proportion of 14.07% [mediation effect: (b = 0.0007, 95%CI: 0.0002-0.0011); proportion mediation = 14.07% (4.26-23.40%)]. Conclusion: Our research confirms a genetic causal relationship between specific gut microbes and hypertension, emphasizing the potential mediating role of interleukin-1 receptor type 2 (IL-1R2) and offering insights for clinical hypertension interventions.

Yin Yang 1-Induced Long Noncoding RNA DUXAP9 Drives the Progression of Oral Squamous Cell Carcinoma by Blocking CDK1-Mediated EZH2 Degradation.

LncRNAs play a critical role in oral squamous cell carcinoma (OSCC) progression. However, the function and detailed molecular mechanism of most lncRNAs in OSCC are not fully understood. Here, a novel nuclear-localized lncRNA, DUXAP9 (DUXAP9), that is highly expressed in OSCC is identified. A high level of DUXAP9 is positively associated with lymph node metastasis, poor pathological differentiation, advanced clinical stage, worse overall survival, and worse disease-specific survival in OSCC patients. Overexpression of DUXAP9 significantly promotes OSCC cell proliferation, migration, invasion, and xenograft tumor growth and metastasis, and upregulates N-cadherin, Vimentin, Ki67, PCNA, and EZH2 expression and downregulates E-cadherin in vitro and in vivo, whereas knockdown of DUXAP9 remarkably suppresses OSCC cell proliferation, migration, invasion, and xenograft tumor growth in vitro and in vivo in an EZH2-dependent manner. Yin Yang 1 (YY1) is found to activate the transcriptional expression of DUXAP9 in OSCC. Furthermore, DUXAP9 physically interacts with EZH2 and inhibits EZH2 degradation via the suppression of EZH2 phosphorylation, thereby blocking EZH2 translocation from the nucleus to the cytoplasm. Thus, DUXAP9 can serve as a promising target for OSCC therapy.

Gut brain interaction theory reveals gut microbiota mediated neurogenesis and traditional Chinese medicine research strategies.

Adult neurogenesis is the process of differentiation of neural stem cells (NSCs) into neurons and glial cells in certain areas of the adult brain. Defects in neurogenesis can lead to neurodegenerative diseases, mental disorders, and other maladies. This process is directionally regulated by transcription factors, the Wnt and Notch pathway, the extracellular matrix, and various growth factors. External factors like stress, physical exercise, diet, medications, etc., affect neurogenesis and the gut microbiota. The gut microbiota may affect NSCs through vagal, immune and chemical pathways, and other pathways. Traditional Chinese medicine (TCM) has been proven to affect NSCs proliferation and differentiation and can regulate the abundance and metabolites produced by intestinal microorganisms. However, the underlying mechanisms by which these factors regulate neurogenesis through the gut microbiota are not fully understood. In this review, we describe the recent evidence on the role of the gut microbiota in neurogenesis. Moreover, we hypothesize on the characteristics of the microbiota-gut-brain axis based on bacterial phyla, including microbiota's metabolites, and neuronal and immune pathways while providing an outlook on TCM's potential effects on adult neurogenesis by regulating gut microbiota.

An Efficient Markerless Deletion System Suitable for the Industrial Strains of Streptomyces.

The genus Streptomyces is intensively studied due to its excellent ability to produce secondary metabolites with diverse bioactivities. In particular, adequate precursors of secondary metabolites as well as sophisticated post modification systems make some high-yield industrial strains of Streptomyces the promising chassis for the heterologous production of natural products. However, lack of efficient genetic tools for the manipulation of industrial strains, especially the episomal vector independent tools suitable for large DNA fragment deletion, makes it difficult to remold the metabolic pathways and streamline the genomes in these strains. In this respect, we developed an efficient deletion system independent of the episomal vector for large DNA fragment deletion. Based on this system, four large segments of DNA, ranging in length from 10 kb to 200 kb, were knocked out successfully from three industrial Streptomyces strains without any marker left. Notably, compared to the classical deletion system used in Streptomyces, this deletion system takes about 25% less time in our cases. This work provides a very effective tool for further genetic engineering of the industrial Streptomyces.

Display of Microbial Glucose Dehydrogenase and Cholesterol Oxidase on the Yeast Cell Surface for the Detection of Blood Biochemical Parameters.

High levels of blood glucose are always associated with numerous complications including cholesterol abnormalities. Therefore, it is important to simultaneously monitor blood glucose and cholesterol levels in patients with diabetes during the management of chronic diseases. In this study, a glucose dehydrogenase from Aspergillus oryzae TI and a cholesterol oxidase from Chromobacterium sp. DS-1 were displayed on the surface of Saccharomyces cerevisiae, respectively, using the yeast surface display system at a high copy number. In addition, two whole-cell biosensors were constructed through the immobilization of the above yeast cells on electrodes, for electrochemical detection of glucose and cholesterol. The assay time was 8.5 s for the glucose biosensors and 30 s for the cholesterol biosensors. Under optimal conditions, the cholesterol biosensor exhibited a linear range from 2 to 6 mmol·L-1. The glucose biosensor responded efficiently to the presence of glucose at a concentration range of 20-600 mg·dL-1 (1.4-33.3 mmol·L-1) and showed excellent anti-xylose interference properties. Both biosensors exhibited good performance at room temperature and remained stable over a three-week storage period.