Diagnosis of post-neurosurgical bacterial meningitis in patients with aneurysmal subarachnoid hemorrhage based on the immunity-related proteomics signature of the cerebrospinal fluid.

Introduction: Post-neurosurgical bacterial meningitis (PNBM) is a serious complication for patients who receive neurosurgical treatment, but the diagnosis is difficult given the complicated microenvironment orchestrated by sterile brain injury and pathogenic infection. In this study, we explored potential diagnostic biomarkers and immunological features using a proteomics platform. Methods: A total of 31 patients with aneurysmal subarachnoid hemorrhage (aSAH) who received neurosurgical treatment were recruited for this study. Among them, 15 were diagnosed with PNBM. The remaining 16 patients were categorized into the non-PNBM group. Proteomics analysis of the cerebrospinal fluid (CSF) was conducted on the Olink platform, which contained 92 immunity-related molecules. Results: We found that the expressions of 27 CSF proteins were significantly different between the PNBM and non-PNBM groups. Of those 27 proteins, 15 proteins were upregulated and 12 were downregulated in the CSF of the PNBM group. The receiver operating characteristic curve analysis indicated that three proteins (pleiotrophin, CD27, and angiopoietin 1) had high diagnostic accuracy for PNBM. Furthermore, we also performed bioinformatics analysis to explore potential pathways and the subcellular localization of the proteins. Conclusion: In summary, we found a cohort of immunity-related molecules that can serve as potential diagnostic biomarkers for PNBM in patients with aSAH. These molecules also provide an immunological profile of PNBM.

Evidence for an intra-tumoral microbiome in pituitary neuroendocrine tumors with different clinical phenotypes.

PURPOSE: Bacteria have been observed in the tumor environment for decades and have been demonstrated to play important roles in the pathogenesis and development of several different tumors. So far there is a clear lack of specific studies relating to the presence of bacteria in pituitary neuroendocrine tumors (PitNETs). METHODS: In this study, we performed five region-based amplification and bacterial 16 S rRNA sequencing to identify the microbiome of PitNET tissues across four clinical phenotypes. Multiple filter procedures were performed to inhibit the risk of contamination with bacteria and bacterial DNA. Histological analysis was also conducted to validate the localization of bacteria in the intra-tumoral region. RESULTS: We identified common and diverse bacterial types across the four clinical phenotypes of PitNET. We also predicted the potential functions of these bacteria in tumor phenotypes and found that these functions were reported in certain previous mechanistic studies. Our data indicate that the pathogenesis and development of tumors may correlate with the behavior of intra-tumoral bacteria. Histological results, including lipopolysaccharide (LPS) staining and fluorescence in situ hybridization (FISH) for bacterial 16 S rRNA clearly demonstrated the localization of bacteria in the intra-tumoral region. Staining for Iba-1 suggested that the proportion of microglia was more abundant in FISH-positive regions than in FISH-negative regions. Furthermore, in FISH-positive regions, the microglia exhibited a longitudinally branched morphology that was different to the compact morphology observed in FISH-negative regions. CONCLUSION: In summary, we provide an evidence for the existence of intra-tumoral bacteria in PitNET.

Bilateral Subthalamic Nucleus Deep Brain Stimulation Improves Gastric Emptying Time in Parkinson Disease.

BACKGROUND: It is well-established that deep brain stimulation (DBS) can improve motor function in those with Parkinson disease (PD); however, its effects on gastrointestinal disorders remain unclear. METHODS: From January 2019 to December 2020, 26 patients with PD who had undergone subthalamic nucleus (STN) DBS were included in our study. The evaluated items included the pre- and postoperative dose of levodopa, Unified Parkinson's Disease Rating Scale, part III, scores with and without medication and stimulation, and gastric emptying time (expressed as the peak time of carbon-13C dioxide excretion in the 13C-acetate breath test). Sex-, age-, and body weight-matched controls were recruited to test the gastric emptying time in healthy individuals. RESULTS: All the patients benefited from DBS. The Unified Parkinson's Disease Rating Scale, part III, scores had decreased from 48.5 ± 13.77 to 25.23 ± 8.59 without medication and 31.23 ± 11.4 to 13.92 ± 5.27 with medication. The levodopa equivalent dose had decreased from 1009.8 ± 291 mg to 707.65 ± 193.79 mg. The gastric emptying time was significantly prolonged in the patients with PD before DBS compared with the healthy control group (29.23 ± 6.58 minutes) and had improved to 35.19 ± 10.14 minutes with medication and 38.07 ± 11.17 minutes without medication after 3 months of STN stimulation. At 6 months postoperatively, the gastric emptying time was 32.3 ± 10.02 minutes without medication and 33.84 ± 10.79 minutes with medication. CONCLUSIONS: A delayed gastric emptying time is associated with greater PD severity. Antiparkinsonian medications did not affect gastric emptying in patients with PD. STN DBS can improve both movement function and gastrointestinal motility in patients with PD in the long term. The exact mechanism by which DBS improves gastric emptying requires further exploration.

S100A11 Promotes Glioma Cell Proliferation and Predicts Grade-Correlated Unfavorable Prognosis.

The prognosis of glioma is significantly correlated with the pathological grades; however, the correlations between the prognostic biomarkers with pathological grades have not been elucidated. S100A11 is involved in a variety of malignant biological processes of tumor, whereas its biological and clinicopathological features on glioma remain unclear. In this study, the S100A11 expression and clinical information were obtained from the public databases (TCGA, GEPIA2) to analyze its correlations with the pathological grade and the prognosis of glioma patients. We then verified the expression of S100A11 by immunohistochemistry staining. The effects of S100A11 on the proliferation of glioma cells were confirmed by cytological function assays (CCK-8, Flow cytometry, Clone formation assay) in vitro, the role of S100A11 in regulation of glioma growth was determined by xenograft model assay. We observed that S100A11 expression positively correlated with the pathological grades, while negatively correlated with the survival time of patients. In cytological analysis, we found the proliferations of glioma cell lines were significantly inhibited in vitro (P < 0.05) after interfering S100A11 expression via shRNAs. The cell cycle was blocked at G0/G1 stage. The ability of clone formation was significantly decreased, and the tumorigenicity in vivo was weakened (P < 0.05). In summary, S100A11 was over-expressed in gliomas and positively correlated with the pathological grades. Interfering the expression of S100A11 significantly inhibited the proliferation of glioma in vitro and the tumorigenicity in vivo (P < 0.05). In conclusion, S100A11 might be considered as a potential biomarker in glioma.

Oxidative stress induced autophagy in cancer associated fibroblast enhances proliferation and metabolism of colorectal cancer cells.

Tumors are comprised of malignant cancer cells and stromal cells which constitute the tumor microenvironment (TME). Previous studies have shown that cancer associated fibroblast (CAF) in TME is an important promoter of tumor initiation and progression. However, the underlying molecular mechanisms by which CAFs influence the growth of colorectal cancer cells (CRCs) have not been clearly elucidated. In this study, by using a non-contact co-culture system between human colorectal fibroblasts (CCD-18-co) and CRCs (LoVo, SW480, and SW620), we found that fibroblasts existing in tumor microenvironment positively influenced the metabolism of colorectal cancer cells, through its autophagy and oxidative stress pathway which were initially induced by neighboring tumor cells. Therefore, our data provided a novel possibility to develop fibroblasts as a potential target to treat CRC.