Effect of probiotics on cognitive function in adults with mild cognitive impairment or Alzheimer's disease: A meta-analysis of randomized controlled trials.

BACKGROUND: Recent clinical studies have yielded controversial results regarding the effect of probiotics on cognitive function in Alzheimer's disease (AD) or mild cognitive impairment (MCI) subjects. To clarify the efficacy of probiotics on cognition, we conducted a meta-analysis of randomized controlled trials (RCTs). METHODS: Instructions of the PRISMA 2020 statement were followed. Literature from the PubMed, Embase and Cochrane databases were systematically searched and manually screened for relevant published RCTs. We performed statistical analysis using RevMan, and assessed the risk of bias using the R software. RESULTS: A total of 12 studies comprising 852 patients with MCI or AD were identified. The results of meta-analysis showed that probiotics improved global cognitive function (SMD=0.67; 95% CI, 0.32, 1.02), recall/delayed memory (SMD=0.67; 95% CI: 0.32, 1.02), attention (SMD=0.31; 95% CI: 0.04, 0.58) and visuospatial/constructional (SMD=0.24; 95% CI: 0.06, 0.42) cognitive domain. CONCLUSION: This meta-analysis found that probiotic supplementation is associated with an improvement in cognitive performance among patients with AD and MCI. However, current evidence is limited, and more reliable large-scale RCTs with higher methodological quality are needed.

Corrigendum: Risk and prediction of multiple primary malignancies after early gastric cancer.

[This corrects the article DOI: 10.3389/fonc.2023.1205358.].

Risk and prediction of multiple primary malignancies after early gastric cancer.

Background: Patients with early gastric cancer have increased risk of developing multiple primary malignancies (MPM) due to improved survival rates. The purpose of this study was to evaluate the clinicopathological features of MPM and to generate a useful tool for predicting the development of MPM after early gastric cancer. Methods: We selected 1025 early gastric cancer patients with complete medical records for a retrospective analysis. The Cox proportional risk regression model was used to analyze the independent risk factors for the development of MPM in early gastric cancer. RStudio software was used to compare the OS of early gastric cancer patients with and without MPM, and a nomogram was established to predict the probability of MPM 1-, 2-, 3-year after early gastric cancer. The predictive effectiveness of the nomogram was evaluated by the C-index and calibration curve. Decision curve analysis (DCA) measured the applicability of the nomogram to clinical practice. Results: Of the 1025 patients with early gastric cancer, 66 patients (6.4%) had 69 primary cancers other than early gastric cancer. They had a median follow-up of 41 months, and their cumulative incidence of MPM was 4.9%, 5.4% and 5.9% after 1-, 2-, and 3- year, respectively. Oesophageal cancer was the most frequently detected MPM, followed by lung and colorectal cancers. Male (p=0.038), age ≥65 years (p=0.003), smoking history (p=0.036), and lymph node metastasis (p=0.013) were independent risk factors for MPM in patients with early gastric cancer. Patients with early gastric cancer with MPM had a worse OS prognosis than patients with early gastric cancer without MPM (p<0.001). The internally validated nomogram predicted the probability of developing MPM after early gastric cancer (C index= 0.697). The calibration chart showed that the predicted probability of MPM in early gastric cancer was similar to the observed result, and the DCA showed strong clinical practicability. Conclusion: After the diagnosis and treatment of early gastric cancer, we should be alert to the possibility of MPM and perform regular and careful monitoring.

Long noncoding RNA Ftx regulates the protein expression profile in HCT116 human colon cancer cells.

BACKGROUND: The long noncoding RNA (lncRNA) five prime to Xist (Ftx) is involved in distant metastasis in colorectal cancer (CRC). This study aimed to investigate Ftx alteration-induced proteomic changes in the highly metastatic CRC cell line HCT116. METHODS: Tandem mass tag (TMT)-based proteomics analysis was performed to detect the differential protein expression in Ftx-overexpressing and Ftx-silenced HCT116 cells. The differentially expressed proteins were classified and characterized by bioinformatics analyses, including gene ontology (GO) annotation, GO/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway/protein domain enrichment analyses, as well as hierarchical clustering. A total of 5471 proteins were quantified, and the proteins with |fold change|≥ 1.2 and p < 0.05 were identified as differentially expressed proteins in response to Ftx overexpression or silencing. RESULTS: The bioinformatics analyses revealed that the differentially expressed proteins were involved in a wide range of GO terms and KEGG signaling pathways and contained multiple protein domains. These terms, pathways, and protein domains were associated with tumorigenesis and metastasis in CRC. CONCLUSIONS: Our results indicate that the alteration of Ftx expression induces proteomic changes in highly metastatic HCT116 cells, suggesting that Ftx and its downstream molecules and signaling pathways could be potential diagnostic biomarkers and therapeutic targets for metastatic CRC.

Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial.

BACKGROUND AND AIM: Bowel preparation is an important determinant of the quality of colonoscopy. The traditional split-dose regimen of 4 L polyethylene glycol (PEG) solutions for bowel preparation is effective but poorly tolerated. The aim of this was to study the efficacy and tolerability of using linaclotide as an adjunctive agent with low-volume PEG for bowel preparation. METHODS: This was an endoscopist-blinded, randomized, controlled trial of 432 patients randomly assigned to three groups: 2 L PEG, 4 L PEG and 2 L PEG + 290 µg linaclotide (2 L PEG + L group). The primary outcome measure was efficacy of bowel preparation according to the Boston Bowel Preparation Scale (BBPS), with secondary outcomes of patients' tolerance, defecating frequency, complications, sleeping quality, cecal intubation rate, preparation-to-colonoscopy interval, withdrawal time, cecal intubation time, and adenoma and polyp detection rates. RESULTS: The percentage of adequate bowel preparation in the 2 L PEG + L group was higher than that of the 2 L PEG group (87.9% vs. 77.0%; P = 0.017), but not the 4 L PEG group (87.9% vs. 91.4%; P = 0.339). In terms of the mean (SD) BBPS score for the total and segmental colons, the bowel cleansing efficacy of 2 L PEG + L was superior to that of 2 L PEG and similar to that of 4 L PEG. Patient's tolerance (including complications, willingness to repeat and sleeping quality) were compatible between the 2 L and 2 L + L group, and the 4 L group was the worst among these three groups. CONCLUSION: Two liters of PEG combined with 290 µg linaclotide was an effective and well-tolerated bowel preparation regimen.

Circ_ZFP644 attenuates caerulein-induced inflammatory injury in rat pancreatic acinar cells by modulating miR-106b/Pias3 axis.

(AP) is a kind of inflammatory misorder existing in pancreas. Non-coding RNAs (ncRNAs) have been reported to play important roles in development of AP. The current study was designed to explore the role of circular RNA zinc finger protein 644 (circRNA circ_ZFP644) in caerulein-induced AR42J cells. AP model in vitro was established by exposure of rat pancreatic acinar AR42J cells to caerulein. Amylase activity was measured using a kit. Enzyme-linked immunosorbent assay (ELISA) was performed to examine the levels of several inflammatory factors. The expression of circ_ZFP644, microRNA (miR)-106b and protein inhibitor of activated STAT 3 (Pias3) was detected by quantitative real-time PCR (qRT-PCR) or western blot assay. And flow cytometry was employed to monitor cell apoptosis. Western blot assay was also conducted to analyze the expression of apoptosis-related proteins. The association among circ_ZFP644, miR-106b and Pias3 was validated by dual-luciferase reporter assay. Caerulein treatment activated amylase activity and promoted the secretion of inflammatory cytokines in AR42J cells. Circ_ZFP644 and Pias3 were downregulated, but miR-106b was upregulated in caerulein-induced AR42J cells. Enforced expression of circ_ZFP644 or miR-106b inhibition could reduce amylase activity and inflammatory cytokine secretion, while promote apoptosis in caerulein-induced AR42J cells, which was almost reversed by Pias3 knockdown. Circ_ZFP644 targeted miR-106b to upregulate Pias3 expression. Circ_ZFP644 might exert its anti-inflammation and pro-apoptosis roles in caerulein-induced AR42J cells by regulating miR-106b/Pias3 axis.

Resveratrol Suppresses Tumor Progression via Inhibiting STAT3/HIF-1α/VEGF Pathway in an Orthotopic Rat Model of Non-Small-Cell Lung Cancer (NSCLC).

BACKGROUND: The STAT3/HIF-1α/VEGF pathway is associated with the development and progress of various tumors including NSCLC. The aim of the present study was to investigate whether resveratrol (RES) could suppress NSCLC progression via inhibiting the expressions of STAT3, HIF-1α, and VEGF in a nude rat model. METHODS: Twenty-four nude rats were randomly divided into control, NSCLC, and NSCLC+RES groups. An orthotopic rat model of NSCLC was established. The animals in the NSCLC+RES group received the same operation as the NSCLC group and were intragastrically administered RES at 250 mg/kg/day for 12 weeks. Lung tissue samples were harvested for gross tumor burden measurement, histological examinations, RT-PCR, and Western blot assays. RESULTS: In the NSCLC+RES group, significant decreases in lung weight index, lung tumor burden, STAT3/HIF-1α/VEGF mRNA, and protein levels were observed when compared with the NSCLC group (all P<0.05). The structural integrity of the lung was less affected and the apoptotic index was significantly higher in the NSCLC+RES group, when compared to the NSCLC group (P<0.05). CONCLUSION: RES suppresses NSCLC partly through inhibiting the expressions of STAT3, HIF-1α, and VEGF. The STAT3/HIF-1α/VEGF pathway might be a candidate drug target for developing new chemotherapy agents derived from RES for the treatment of NSCLC.

Fibroblast growth factor receptor-like-1: a new therapeutic target and unfavorable prognostic indicator for rectal adenocarcinoma.

Fibroblast growth factor receptor-like-1 (FGFRL1) is important to cell motility and links with tumorigenic potential in various types of cancers. To investigate the biological function and underlying mechanism of FGFRL1 in rectal adenocarcinoma, we conducted this study. TCGA and Oncomine databases were used to analyze FGFRL1 expression and its association with clinical characteristics or overall survival (OS) in rectal adenocarcinoma patients. siRNA strategy was implemented to knockdown FGFRL1 expression in rectal adenocarcinoma cells. CCK8, colony formation, wound healing, and transwell assays were implemented to measure cell behaviors. qRT-PCR and western blot were utilized to identify mRNA and protein expression levels. FGFRL1 was significantly increased in rectal adenocarcinoma tissue samples, either colon or rectum. High-regulation of FGFRL1 expression induced poorer outcome of rectal adenocarcinoma patients. Downregulation of FGFRL1 inhibited the proliferation, colony formation, migration, and invasion of SW837 cells. The MAPK pathway-related proteins, phosphorylation of MEK and ERK, were also decreased after si-FGFRL1 transfection. These findings demonstrated that FGFRL1, acting as a potential inducator, may promote the progression of rectal adenocarcinoma via activating the MAPK signaling pathway.

Quantitative Proteomics Analysis Revealed the Potential Role of lncRNA Ftx in Promoting Gastric Cancer Progression.

PURPOSE: The molecular pathogenesis of gastric cancer is still ambiguous till now. Here, it is demonstrated that long noncoding RNA (lncRNA) Ftx acts as a novel tumor promotor of gastric cancer and a potent regulator of hexokinase-2 (HK2). EXPERIMENTAL DESIGN: The role of lncRNA Ftx is detected in the loss and gain-of-function models of gastric cancer cells. Tandem mass tags combined with multidimensional LC and MS analyses are performed to decipher comparative proteomic profiles of gastric cancer cells in response to lncRNA Ftx knockdown and overexpression. Real-time roteomics-clinical applications (PCR) and western blot are used to validate the proteomic data. RESULTS: A total of 5124 proteins are quantified and indicated in diverse biological functions and metabolic related signaling pathways. Interestingly, HK2, which is downregulated when lncRNA Ftx is deleted and upregulated while lncRNA Ftx is overexpressed, is further validated in gastric cancer cells. CONCLUSIONS AND CLINICAL RELEVANCE: The present study suggests lncRNA Ftx promotes gastric cancer progression by upregulating HK2, which provides a new perspective for the mechanism of gastric cancer progression, and thus identifies potential therapeutic targets for gastric cancer.

MicroRNA-186-5p Inhibits Proliferation And Metastasis Of Esophageal Cancer By Mediating HOXA9.

OBJECTIVE: MicroRNA (miRNA) is an endogenous, non-coding small RNA that plays a key role in regulating organism biology and pathology. The aim of this study was to investigate the expression characteristics of microRNA-186-5p in esophageal cancer (ECa) and its correlation with clinical progression and prognosis, and to further explore its underlying mechanisms. METHODS: Real-time quantitative PCR (qRT-PCR) was used to detect microRNA-186-5p level in 45 pairs of ECa tissue samples and adjacent ones, and to analyze the expression of microRNA-186-5p and clinical progression of ECa and prognosis. The relationship between microRNA-186-5p level in ECa cell lines was further verified by qRT-PCR. Finally, the potential mechanism was explored using luciferase reporter gene assay and cell recovery experiment. RESULTS: QRT-PCR results revealed that the expression of microRNA-186-5p in ECa tissues was remarkably lower than that in adjacent tissues, and the difference was statistically significant. Compared with patients with high expression of microRNA-186-5p, patients with low expression of microRNA-186-5p had higher incidence of pathological stage and lower overall survival rate. Besides, compared with the miR-NC group, the microRNA-186-5p mimics group had a significant decrease in proliferation and metastasis ability of ECa cells. Subsequent qRT-PCR validation in ECa cell lines and tissues indicated a significant increase in HOXA9 expression and a negative correlation with microRNA-186-5p. CONCLUSION: The expression of microRNA-186-5p was remarkably decreased in ECa, which was remarkably correlated with pathological stage, distant metastasis and poor prognosis of ECa. The results suggested that microRNA-186-5p may inhibit cell proliferation of ECa by regulating HOXA9.

Endoscopic ultrasound guided fine needle aspiration versus endoscopic ultrasound guided fine needle biopsy in sampling pancreatic masses: A meta-analysis.

BACKGROUND: The comparison between endoscopic ultrasound guided fine needle aspiration (EUS-FNA) and endoscopic ultrasound guided fine needle biopsy (EUS-FNB) for the diagnosis of pancreatic masses is still controversial. Many factors can affect the final results. METHODS: Databases, such as PubMed, EMBASE, Cochrane Library, and Science Citation Index updated from 2000 to 2016 were searched to include eligible articles. In the meta-analysis, the main outcome measurements were the diagnostic accuracy, number of needle passes, specimen adequacy, the rate of complications, and technical success. RESULTS: Eight randomized controlled trials (RCTs) were identified, and a total of 921 cases were included in the meta-analysis. The diagnostic accuracy was not significantly different between the FNA and FNB groups. The specimen adequacy was higher in the FNB group compared with the FNA group. The number of needle passes to obtain sufficient tissue was lower in the FNB group. The rate of adverse events and technical success did not significantly differ between the 2 groups. But, the forest plot showed a trend toward lower technical success rate and a trend toward higher diagnostic accuracy in the FNB group, compared with FNA. CONCLUSION: We provide the evidence that FNB is comparable to FNA in terms of diagnostic accuracy, adverse events, and technical success. FNB gives higher specimen adequacy than that of FNA, despite performance of fewer needle passes.

Analysis of Predictors for Lymph Node Metastasis in Patients with Superficial Esophageal Carcinoma.

In order to predict related risk factors for lymph node metastasis (LNM) in patients with superficial esophageal carcinoma (SEC) and provide reference for endoscopic minimally invasive treatment, we included a total of 93 patients with superficial esophageal carcinoma who have underwent esophagectomy and lymph node dissection from 2010 to 2015. The depth of invasion was remeasured and classified into 6 groups according to their wall penetration. The prediction model was founded based on the independent risk factors. The results shows that lymph node metastasis of m1, m2, m3, sm1, sm2, and sm3 of superficial esophageal carcinoma was 0%, 0%, 5.3%, 8.7%, 17.6%, and 37.5%, respectively. The tumor size, differentiation, and lymphvascular invasion were also significantly related to lymph node metastasis by univariate analysis. Multivariate analysis showed that the depth of invasion and lymphovascular invasion were independent risk factors of lymph node metastasis. A prediction model for lymph node metastasis was established as follows: p = ex /(1 + ex ), and x = -5.469 + 0.839 × depth of invasion + 1.992 × lymphavascular metastasis. The area under ROC curve was 0.858 (95% CI: 0.757-0.959). It was also shown that the depth of invasion was related to tumor differentiation, macroscopic type, and tumor size.