Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that Fusobacterium nucleatum (F. nucleatum) contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether F. nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid. AIM: To investigate the mechanism by which F. nucleatum affects CRC occurrence and development. METHODS: Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function. RESULTS: Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB's inhibition of CRC cell proliferation. CONCLUSION: F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.

Research hotspots of polycystic ovary syndrome and hyperandrogenism from 2008 to 2022: bibliometric analysis.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disorder in female adults, and hyperandrogenism (HA) is the typical endocrine feature of PCOS. This study aims to investigate the trends and hotspots in the study of PCOS and HA. METHODS: Literature on Web of Science Core Collection (WoSCC) from 2008 to 2022 was retrieved, and bibliometric analysis was conducted using VOSviewer and CiteSpace software. RESULTS: A total of 2,404 papers were published in 575 journals by 10,121 authors from 2,434 institutions in 86 countries. The number of publications in this field is generally on the rise yearly. The US, China and Italy contributed almost half of the publications. Monash University had the highest number of publications, while the University of Adelaide had the highest average citations and the Karolinska Institute had the strongest cooperation with other institutions. Lergo RS contributed the most to the field of PCOS and HA. The research on PCOS and HA mainly focused on complications, adipose tissue, inflammation, granulosa cells, gene and receptor expression. CONCLUSION: Different countries, institutions, and authors should facilitate cooperation and exchanges. This study will be helpful for better understanding the frontiers and hotspots in the areas of PCOS and HA.

Scientific Knowledge Graph of Dysmenorrhea: A Bibliometric Analysis from 2001 to 2021.

Purpose: This study aims to help researchers master the most active hotspots and trends quickly through bibliometric analysis in the field of dysmenorrhea. Methods: We retrieved literature on Web of Science from 2001 to 2021, and bibliometric analysis software CiteSpace was used in combination with VOSviewer. Results: We finally acquired 944 papers and an upward trend in articles continued in this field overall. Through the map, China contributed the most, followed by the USA and Turkey. For institutions, Beijing University of Chinese Medicine in China contributed the most, followed by National Yang-Ming University in Taiwan, China. Hsieh JC and Hellman KM were both the most prolific authors with 14 articles. Five major research groups, respectively, with Hsieh JC, Hellman KM, Zhu J, Liang F and Dun W were the key group. Dawood MY was the most dominant author and most frequently cited author. The Cochrane Database of Systematic Reviews Journal was the most productive, and the Fertility and Sterility Journal was the most cited. Advances in pathogenesis and management for primary dysmenorrhea written by Dawood MY was most cited and influential. Pathophysiology, the potential central mechanism, syndrome, evaluation index, diagnosis of adenomyosis-associated dysmenorrhea, treatment, etc., were the main trends and hotspots. Conclusion: Dysmenorrhea research has received a lot of attention from scholars. Strengthening international cooperation may promote the development of this field. The pathophysiology of dysmenorrhea, its impact on public health and its treatment are current research hotspots and are likely to be the focus of future study.

Robotic Construction and Screening of Lanthipeptide Variant Libraries in Escherichia coli.

Lanthipeptides are a major class of ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by thioether cross-links called lanthionine (Lan) and methyllanthionine (MeLan). Previously, we developed a method to produce mature lanthipeptides in recombinant Escherichia coli, but manual steps hinder large-scale analogue screening. Here we devised an automated workflow for creating and screening variant libraries of haloduracin, a two-component class II lanthipeptide. An integrated work cell of a synthetic biology foundry was programmed to robotically execute DNA library construction, host transformation, peptide production, mass spectrometry analysis, and activity screening by agar diffusion assay. For recombinantly produced Halα peptides, the sequence-activity relationship of 380 single-residue variants and >1300 triple-residue combinatorial variants were rapidly analyzed in microplates within weeks. The peptide expression levels in E. coli were also visualized via robotic creation and analysis of GFP-lanthipeptide fusions for select peptide mutants. Following shake-flask fermentation and purification, one Halα mutant was confirmed with enhanced specific antimicrobial activity relative to the wild-type peptide. Overall, this approach may be generally applicable for the high-throughput characterization and engineering of RiPP natural products.

Fusobacterium nucleatum Affects Cell Apoptosis by Regulating Intestinal Flora and Metabolites to Promote the Development of Colorectal Cancer.

Background/Aims: Intestinal flora, especially Fusobacterium nucleatum (Fn), can affect the development of colorectal cancer (CRC). In this study, we examined the composition of intestinal flora and their metabolites in the tissues, serum and feces of CRC patients. Materials and Methods: CRC tissues, adjacent normal colonic tissues, fecal and serum samples were collected from CRC patients who received surgical treatment between January 2018 and January 2020. Fecal and serum samples were collected from healthy individuals for comparison. In addition, fecal samples were collected from BALB/c female mice. SW480, a human CRC cell line, was utilized for in vitro studies. The experiments involved 1H-NMR-based metabolomics analysis, targeted and untargeted mass spectrometry analysis, and intestinal flora 16S rDNA V4 region sequencing. Results: The abundance of Bacteroides and propionic acid concentration were decreased and that of Lactobacillus and lactic acid concentration were increased in CRC tissues. In addition, the abundances of Ruminococcus, Prevotella, and Sutterell were decreased in CRC patients. The levels of leucine and isoleucine were decreased in the serum and tumor tissues of CRC patients. Aspartate, glutamate and glutathione levels were elevated in the tissues of CRC patients only. The serum glutamine, tyrosine, valine, alanine, and histidine levels were decreased significantly. Lactic acid inhibited and propionic acid promoted apoptosis among SW480 CRC cells. Conclusion: Fn affected the apoptosis of CRC cells and promoted the progression of CRC by affecting the distribution of intestinal flora, which altered the concentrations of metabolites such as lactic acid, propionic acid. Intestinal flora could regulate amino acid metabolism.

Fusobacterium nucleatum Promotes the Progression of Colorectal Cancer Through Cdk5-Activated Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: Growing evidence supports the direct link of Fusobacterium nucleatum with colorectal cancer (CRC). However, to date, the underlying mechanism of action remains poorly understood. In this study, we examined the effects of F. nucleatum on the progression of CRC and investigated whether cyclin-dependent kinase 5 (Cdk5) is involved in the effect through activating the Wnt/ß-catenin signaling pathway. MATERIALS AND METHODS: CRC tissues and matched histologically normal specimens were collected from patients who were diagnosed with CRC and underwent surgical treatment in our hospital between January 2018 and January 2019. Two human CRC cell lines, including DLD-1 and SW480, were utilized mainly for in vitro mechanistic investigations. RESULTS: The abundance of F. nucleatum was significantly greater in CRC tissues than in cancer-free specimens, which was significantly correlated with the progression of CRC. In vitro investigations revealed that F. nucleatum significantly enhanced the proliferation and migration of CRC cells. Furthermore, F. nucleatum significantly induced the expression of Cdk5 and activation of the Wnt/ß-catenin signaling pathway. Notably, knockdown of Cdk5 significantly abrogated the effects of F. nucleatum on cellular processes and Wnt/ß-catenin signaling in relation to the progression of CRC. CONCLUSION: The results of this study demonstrate that F. nucleatum orchestrates a molecular network involving the direct role of Cdk5 in activating Wnt/ß-catenin signaling to modulate CRC progression. Thus, in-depth investigations of F. nucleatum-associated molecular pathways may offer valuable insight into the pathogenesis of CRC, which may help further the development of treatment for this disease.