Gut microbiota and its metabolites in non-small cell lung cancer and brain metastasis: from alteration to potential microbial markers and drug targets.

Background: The elevated mortality rate associated with non-small-cell lung cancer (NSCLC) is a well-established global concern. Considerable attention has been directed toward exploring the association between gut microbiota and various malignant tumors. We herein investigated the associations between the intestinal microbiome and its metabolites, particularly short-chain fatty acids (SCFAs), in patients with NSCLC at different stages, including early and brain metastasis (BM) stages. The findings aim to offer a fresh perspective on the diagnosis and management of NSCLC. Methods: Fecal samples were collected from 115 participants, comprising healthy controls (n = 35) and patients with treatment-naive NSCLC at the early stage (ELC, n = 40) and the BM stage (n = 40). Characterization of the intestinal microbiome and fecal SCFA levels was performed using 16S rRNA gene sequencing and gas chromatography. Results: The microbial diversity in patients with NSCLC was found to be less abundant and uniform, particularly in the BM stage. Significant alterations in the community structure of the gut microbiota were observed in patients with NSCLC, with an increase in pathogens in Fusobacteria and Proteobacteria and a decrease in SCFA-producing bacteria in Firmicutes and Actinobacteria, particularly in the BM stage. Meanwhile, microbial communities displayed intricate associations in patients with NSCLC. A biomarker panel (Faecalibacterium, Bifidobacterium, Butyricicoccus, Klebsiella, Streptococcus, and Blautia) successfully distinguished patients in the ELC and BM stages from healthy controls (area under the curve: 0.884). The overall concentration of fecal SCFAs was significantly lower in patients with BM compared to patients with ELC and healthy controls. Subgroup analysis of acetate and butyrate yielded similar results. Moreover, multiple disrupted pathways in the NSCLC group were identified using the Kyoto Encyclopedia of Genes and Genomes annotation, including lipid metabolism and genetic information processing, specifically in the BM stage. Conclusion: Compared with healthy controls, distinct host-microbe interactions were evident in different phases of patients with NSCLC. Furthermore, specific forms of the gut microbiome and SCFAs may serve as valuable biomarkers and therapeutic targets in the diagnosis and treatment of NSCLC.

TCF3 Induces DNMT1 Expression to Regulate Wnt Signaling Pathway in Glioma.

The epigenetic alteration is widely understood as the key to cancer initiation. Herein, we intended to clarify the role of transcription factor 3 (TCF3) in the development of glioma and the behind epigenetic mechanism. Through bioinformatics analysis, we identified a TCF3-DNA methyltransferase 1 (DNMT1)-secreted frizzled related protein 1 (SFRP1) axis which was differentially expressed and interacted in gliomas. More specifically, TCF3 activated DNMT1 transcription, and DNMT1 repressed SFRP1 expression. TCF3 and DNMT1 were overexpressed, while SFRP1 was downregulated in glioma. Functionally, TCF3 silencing inhibited cell proliferation and migration, and promoted apoptosis, which were reversed by DNMT1. SFRP1 inhibited the tumor supporting effects of DNMT1 on glioma cells. Moreover, TCF3 downregulation or SFRP1 overexpression inhibited tumorigenesis and enhanced apoptosis of glioma cells, while DNMT1 enhanced tumorigenesis and repressed apoptosis in tumor tissues in vivo. The Wnt pathway was a downstream effector of the TCF3-DNMT1-SFRP1 axis. Collectively, this study determined a novel therapeutic target TCF3 for glioma from the perspective of epigenetic alteration via regulation of SFRP1 expression in a DNMT1-dependent manner.

The role of gut microbiota in patients with benign and malignant brain tumors: a pilot study.

Gut microbiota is associated with the growth of various tumors, including malignant gliomas, through the brain-gut axis. Moreover, the gut microbiota in patients with malignant tumors may considerably differ from those with benign tumors. However, the associations of gut microbiota with benign and malignant brain tumors remain unclear. Hence, in order to explore these underlying relationships, patients with benign meningioma (n = 32), malignant glioma (n = 27), and healthy individuals (n = 41) were selected to participate in this study. The results showed that the diversity of the microbial ecosystem in brain tumor patients were less than the healthy controls, while no significant differences were observed between the meningioma and glioma groups. The microbial composition also differed significantly between individuals with brain tumors and healthy participants. In meningioma group, pathogenic bacteria like Enterobacteriaceae were increased, whereas certain carcinogenic bacteria were overrepresented in the glioma group, including Fusobacterium and Akkermansia. Furthermore, benign and malignant brain tumor patients lacked SCFA-producing probiotics. Thus, a microbial biomarker panel including Fusobacterium, Akkermansia, Escherichia/Shigella, Lachnospira, Agathobacter, and Bifidobacterium was established. Diagnostic models confirmed that this panel could distinguish between brain tumor patients and healthy patients. Additionally, gut microbiota can affect the differentiation and proliferation of brain tumors via several metabolic pathways based on annotations from the Kyoto Encyclopedia of Genes and Genomes (KEGG). This is the first study designed to investigate whether gut microbiota differs between benign and malignant brain tumor patients, and our work concluded that intestinal flora is a valuable tool for the diagnosis and treatment of brain tumors.

Comparison of Neuroendoscopic and Microscopic Surgery for Unilateral Hemilaminectomy: Experience of a Single Institution.

Objective: This study was designed to compare the safety and efficacy of unilateral hemilaminectomy conducted under complete neuroendoscopic visualization (UHNV) relative to unilateral hemilaminectomy under total microscopic visualization (UHMV) for the treatment of patients diagnosed with intraspinal tumors. Methods: In total, 41 patients undergoing intraspinal tumor resection at Northern Jiangsu People's Hospital were included in this study, including 20 and 21 patients in the UHNV and UHMV groups, respectively. Intraoperative parameters including incision length, operative duration, number of vertebral laminae removed and intraoperative blood loss, as well as indicators of curative efficacy such as total tumor resection rates and postoperative symptom improvement rates, and safety indicators including complication rates, recurrence rates, spinal deformity rates, spinal instability incidence, and length of stay (LOS), were compared between the two groups. Results: In contrast to the UHMV group, patients in the UHNV group had a significantly shorter incision length and decreased intraoperative blood loss (P < 0.05), while the operative duration (P > 0.05) showed no statistical difference. Although the postoperative improvement and total tumor resection rates were enhanced, the difference was not statistically significant (P > 0.05). In comparison, the bedridden time and length of stay (LOS) were significantly shortened (P < 0.05) in the UHNV group. However, there were no significant differences in recurrence, incidence of complications, spinal deformity, and spinal instability (P > 0.05). Conclusion: Collectively, our findings indicate that UHNV is not inferior to the UHMV approach. Moreover, due to its safe and minimally invasive nature, UHNV represents a promising alternative to UHMV as a treatment for patients with intradural extramedullary tumors.

Crosstalk Between the Gut and Brain: Importance of the Fecal Microbiota in Patient With Brain Tumors.

Background: Variations in the gut microbiota may affect the metabolism, inflammation and immune response of the host. Microbiota dysbiosis has been extensively investigated in neurological disorders and diseases of the central nervous system (CNS). However, the alterations of the gut microbiota in patients suffering from brain tumors and the associations of the gut microbiota with these diseases remain unknown. Herein, we investigate the alterations of the gut microbiota community in patients with brain tumors and the associations between the two and further explore microbial markers used for the diagnosis of brain tumors. Methods: In our study, we recruited 158 participants, consisting of 101 brain tumor patients (65 benign and 36 malignant cases) and 57 age- and sex-matched healthy controls (HCs). We characterized the gut microbial community by using 16S rRNA gene amplicon sequencing and investigated its correlations with clinical features. Results: The results showed remarkably less microbial ecosystem richness and evenness in patients with brain tumors than in HCs. The gut microbiota community structure underwent profound changes in the brain tumor group, including an increase in the abundances of pathogenic bacteria, such as Fusobacteriota and Proteobacteria and a reduction in the abundances of probiotic bacteria, such as Bifidobacterium or Lachnospira. Moreover, our study indicated more significant correlations and clustering of pathogens in the malignant brain tumor group. Furthermore, a biomarker panel was used to discriminate the brain tumor patients from the healthy controls (AUC: 0.77). Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation revealed an accumulation of harmful metabolites and disorders of the basic physiological pathways in the brain tumor group. Conclusions: Our study revealed that brain tumor patients may possess divergent host-microbe interactions from those of healthy controls, especially in malignant brain tumor patients. In addition, the intestinal flora may be involved in immune responses and metabolism in the microenvironment of brain tumors. All evidence, including the biomarker panel, suggests that the intestinal flora may be a useful diagnostic and predictive tool and an important preventive target for brain tumors.

Effect of Twist-Drill Craniostomy With Hollow Screws for Evacuation of Chronic Subdural Hematoma: A Meta-Analysis.

OBJECTIVE: This study systematically reviews the clinical efficacy and safety of twist-drill craniostomy with hollow screws in chronic subdural hematoma treatment. METHODS: A computerized search of PubMed, Embase, Web of Science, Cochrane Library, World Health Organization International Trial Registry platform, CBM, CNKI, and Wanfang Database was performed to retrieve randomized controlled trials or case-control trials using twist-drill craniostomy (TDC) with hollow screws for the evacuation of chronic subdural hematoma from the date of databases' inception to July 2021. Two investigators independently screened the studies and extracted data in strict accordance with pre-established inclusion and exclusion criteria. RevMan 5.3 software or STATA was used for meta-analysis after evaluating the methodological quality of the included studies. RESULTS: A total of 4 randomized controlled trials and 16 case-control trials with a total of 2,536 cases were included. Results of the meta-analysis showed that the surgical success rate and postoperative recurrence rate of TDC with hollow screws were slightly higher compared to the burr hole craniostomy (BHC) group, but showed no statistical significance (RR = 1.03, P = 0.05; RR = 1.13, P = 0.50). However, subgroup analysis showed that the use of YL-1 needle had a higher success rate and lower recurrence rate (RR = 1.05, P = 0.02 < 0.05; RR = 0.584, P = 0.002), and TDC with hollow screws had a lower incidence rate of postoperative complications and postoperative acute intracranial hemorrhage compared with BHC, also revealing an overall shorter hospital stay (RR = 0.57, P = 0.0002 < 0.05; RR = 0.584, P = 0.027 < 0.05; WMD = -3.752, P < 0.001). However, the postoperative mortality rate was practically the same between the two groups (OR = 1.01, P = 0.95 > 0.05). CONCLUSION: Twist-drill craniostomy with hollow screws is not inferior or superior to BHC in efficacy, and this strategy is safer and minimally invasive, which is reflected in a lower incidence of acute intracranial hemorrhage, overall complication rate, and length of hospital stay. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021270835.