Microfluidics-Derived Microparticles with Prebiotics and Probiotics for Enhanced In Situ Colonization and Immunoregulation of Colitis.

Oral administration of probiotics orchestrates the balance between intestinal microbes and the immune response. However, effective delivery and in situ colonization are limited by the harsh environment of the gastrointestinal tract. Herein, we provide a microfluidics-derived encapsulation strategy to address this problem. A novel synergistic delivery system composed of EcN Nissle 1917 and prebiotics, including alginate sodium and inulin gel, for treating inflammatory bowel disease and colitis-associated colorectal cancer is proposed. We demonstrated that EcN@AN microparticles yielded promising gastrointestinal resistance for on-demand probiotic delivery and colon-retentive capability. EcN@AN microparticles efficiently ameliorated intestinal inflammation and modulated the gut microbiome in experimental colitis. Moreover, the prebiotic composition of EcN@AN enhanced the fermentation of relative short-chain fatty acid metabolites, a kind of postbiotics, to exert anti-inflammatory and tumor-suppressive effects in murine models. This microfluidcis-based approach for the coordinated delivery of probiotics and prebiotics may have broad implications for gastrointestinal bacteriotherapy applications.

miR-129-2-3p inhibits colon cancer cell proliferation by down-regulating the expression of BZW1.

BACKGROUND AND STUDY AIMS: MicroRNA (miRNA) is involved in diverse biological and physiological processes of tumors. Dysregulation of miRNA will induce a series of human diseases. miR-129-2-3p has vital effects in the pathogenesis of various tumors. However, the regulatory function of miR-129-2-3p in colon cancer remains to be clarified. This study investigated the role of miR-129-2-3p targeting BZW1 in proliferation, apoptosis, migration, and invasion of colon cancer. PATIENTS AND METHODS: Here, RT-qPCR was applied to measure the miR-129-2-3p levels in colon cancer tissues. The predicted targets of miR-129-2-3p were identified by bioinformatics and verified using luciferase reporter assay. The effects of miR-129-2-3p on colon cancer were detected by CCK-8, colony formation, transwell chamber test, wound healing, and flow cytometry assays. Finally, the influence of miR-129-2-3p on tumor growth was studied. Nude mice were xenografted with transfected Lovo cells by subcutaneous injection of 5 × 105 cells in 100 µl. HE staining and TUNEL were used to assess metastasis ability. RESULTS: miR-129-2-3p level in colon cancer tissue was significantly reduced. Furthermore, it was verified that BZW1 was a target of miR-129-2-3p, and its expression in colon cancer cells was inhibited by miR-129-2-3p. Additionally, miR-129-2-3p inhibited colon cancer cell proliferation, colony formation, mobility ability and tumor growth, and promoted cell apoptosis by targeting BZW1. miR-129-2-3p overexpression in tumor xenografts in vivo decreased BZW1 expression, and suppressed tumor growth. CONCLUSION: Collectively, these findings indicated that miR-129-2-3p exerts a suppressive role in colon cancer cells by directly targeting BZW1, and may have significant therapeutic implications for patients with colon cancer.

Establishment and verification of prediction model of occult peritoneal metastasis in advanced gastric cancer.

BACKGROUND: To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a nomogram for predicting the occurrence of occult peritoneal metastasis in patients with advanced gastric cancer. METHODS: A total of 111 patients with advanced gastric cancer who underwent laparoscopic exploration or peritoneal lavage cytology examination at the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 2014 to December 2021 were retrospectively analyzed. The patients diagnosed between 2019 and 2021 were assigned to the training set (n = 64), while those diagnosed between 2014 and 2016 constituted the external validation set (n = 47). In the training set, patients were classified into two groups based on preoperative imaging and postoperative pathological data: the occult peritoneal metastasis group (OPMG) and the peritoneal metastasis negative group (PMNG). In the validation set, patients were classified into the occult peritoneal metastasis group (CY1P0, OPMG) and the peritoneal metastasis negative group (CY0P0, PMNG) based on peritoneal lavage cytology results. A nomogram was constructed using univariate and multivariate analyses. The performance of the nomogram was evaluated using Harrell's C-index, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration plots. RESULTS: This study analyzed 22 potential variables of OPM in 111 gastric cancer patients who underwent laparoscopic exploration or peritoneal lavage cytology examination. Logistic regression analysis results showed that Lauren classification, CLDN18.2 score and CA125 were independent risk factors for OPM in patients with gastric cancer. We developed a simple and easy-to-use prediction nomogram of occult peritoneal metastasis in advanced gastric cancer. This nomogram had an excellent diagnostic performance. The AUC of the bootstrap model in the training set was 0.771 and in the validation set was 0.711. This model showed a good fitting and calibration and positive net benefits in decision curve analysis. CONCLUSION: We have developed a prediction nomogram of OPM for gastric cancer. This novel nomogram has the potential to enhance diagnostic accuracy for occult peritoneal metastasis in gastric cancer patients.

Comparison of clinical outcomes and prognosis between surgery and endoscopic submucosal dissection in patients with synchronous multifocal early gastric cancer.

BACKGROUND: Synchronous multiple early gastric cancer (SMEGC) refers to the simultaneous occurrence of two or more malignant cancer lesions in the stomach. For patients with multiple early gastric carcinomas, the choice of appropriate treatment remains controversial. This study is dedicated to comparing the clinical outcomes and prognosis of patients with SMEGC who underwent endoscopic submucosal dissection (ESD) or gastrectomy. METHODS: A total of 180 patients with more than one malignant cancer lesion in the stomach who had received gastrectomy or ESD between 2012 and 2021 were retrospectively evaluated to determine their clinical outcomes and prognosis. Univariate and multivariate logistic regression were utilized to identify risk factors for tumor recurrence. RESULTS: Over the 57.5 months median follow-up period for the 140 enrolled cases, tumor recurrence occurred in 8 (12%) in the ESD group but only 1 (1%) in the surgery group. Relapse-free survival (RFS) was higher in the surgery group (p = 0.023) in all cases; however, there was no significant difference in Overall survival (OS, p = 0.772). Complications were significantly higher in the surgery group than in the ESD group, but fewer in the radical distal gastrectomy group. Multivariate regression analysis revealed that ESD(p = 0.034), the main lesion size > 2 cm(p = 0.019), and undifferentiated tumor(p = 0.022) were independent risk factors for tumor recurrence. CONCLUSIONS: For the treatment of simultaneous multifocal early gastric cancer, ESD has a good short-term effect and higher quality of life. However, ESD has a higher risk of recurrence than surgery. And we found that the partial gastrectomy appears to be considered as adequate treatment for some SMEGC patients.

Genome-wide screening for differentially methylated long noncoding RNAs identifies LIFR-AS1 as an epigenetically regulated lncRNA that inhibits the progression of colorectal cancer.

BACKGROUND: Aberrant DNA methylation is an epigenetic marker that has been linked to the pathogenesis of colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) have been increasingly identified to be associated with tumorigenic processes of CRC. Identifying epigenetically dysregulated lncRNAs and characterizing their effects during carcinogenesis are focuses of cancer research. METHODS: Differentially methylated loci and expressed lncRNAs were identified by integrating DNA methylome and transcriptome analyses using The Cancer Genome Atlas database. Bisulfite sequencing PCR (BSP) was performed to analyze LIFR-AS1 promoter methylation status. The functional roles of LIFR-AS1 in CRC were determined by in vitro and in vivo experiments. RESULTS: We identified a novel hypermethylated lncRNA, LIFR-AS1, that was downregulated and associated with tumorigenesis, metastasis, and poor prognosis in CRC. High methylation burden of LIFR-AS1 indicated a poor survival of CRC patients. Promoter hypermethylation of LIFR-AS1 in tumor tissues was confirmed by BSP. Functional assays revealed that LIFR-AS1 could competitively bind to hsa-miR-29b-3p, and repressed colon cancer cell proliferation, colony formation and invasion. LIFR-AS1 also inhibited tumor growth in a mouse xenograft model of CRC. CONCLUSIONS: Our results showed that the identified DNA methylation-dysregulated lncRNAs may be potential biomarkers and highlighted a role for LIFR-AS1 as a tumor suppressor in CRC.

A Personalized Task Allocation Strategy in Mobile Crowdsensing for Minimizing Total Cost.

Mobile crowdsensing utilizes the devices of a group of users to cooperatively perform some sensing tasks, where finding the perfect allocation from tasks to users is commonly crucial to guarantee task completion efficiency. However, existing works usually assume a static task allocation by sorting the cost of users to complete the tasks, where the cost is measured by the expense of time or distance. In this paper, we argue that the task allocation process is actually a dynamic combinational optimization problem because the previous allocated task will influence the initial state of the user to finish the next task, and the user's preference will also influence the actual cost. To this end, we propose a personalized task allocation strategy for minimizing total cost, where the cost for a user to finish a task is measured by both the moving distance and the user's preference for the task, then instead of statically allocating the tasks, the allocation problem is formulated as a heterogeneous, asymmetric, multiple traveling salesman problem (TSP). Furthermore, we transform the multiple-TSP to the single-TSP by proving the equivalency, and two solutions are presented to solve the single-TSP. One is a greedy algorithm, which is proved to have a bound to the optimal solution. The other is a genetic algorithm, which spends more calculation time while achieving a lower total cost. Finally, we have conducted a number of simulations based on three widely-used real-world traces: roma/taxi, epfl, and geolife. The simulation results could match the results of theoretical analysis.