Plant-derived exosomal nanoparticles: potential therapeutic for inflammatory bowel disease.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic autoimmune disorder characterized by inflammation. However, currently available disease-modifying anti-IBD drugs exhibit limited efficacy in IBD therapy. Furthermore, existing therapeutic approaches provide only partial relief from IBD symptoms and are associated with certain side effects. In recent years, a novel category of nanoscale membrane vesicles, known as plant-derived exosome-like nanoparticles (PDENs), has been identified in edible plants. These PDENs are abundant in bioactive lipids, proteins, microRNAs, and other pharmacologically active compounds. Notably, PDENs possess immunomodulatory, antitumor, regenerative, and anti-inflammatory properties, making them particularly promising for the treatment of intestinal diseases. Moreover, PDENs can be engineered as targeted delivery systems for the efficient transport of chemical or nucleic acid drugs to the site of intestinal inflammation. In the present study, we provided an overview of PDENs, including their biogenesis, extraction, purification, and construction strategies, and elucidated their physiological functions and therapeutic effects on IBD. Additionally, we summarized the applications and potential of PDENs in IBD treatment while highlighting the future directions and challenges in the field of emerging nanotherapeutics for IBD therapy.

Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic inflammatory diseases of the gastrointestinal tract. Repeated inflammation can lead to complications, such as intestinal fistula, obstruction, perforation, and bleeding. Unfortunately, achieving durable remission and mucosal healing (MH) with current treatments is difficult. Stem cells (SCs) have the potential to modulate immunity, suppress inflammation, and have anti-apoptotic and pro-angiogenic effects, making them an ideal therapeutic strategy to target chronic inflammation and intestinal damage in IBD. In recent years, hematopoietic stem cells (HSCs) and adult mesenchymal stem cells (MSCs) have shown efficacy in treating IBD. In addition, numerous clinical trials have evaluated the efficiency of MSCs in treating the disease. This review summarizes the current research progress on the safety and efficacy of SC-based therapy for IBD in both preclinical models and clinical trials. We discuss potential mechanisms of SC therapy, including tissue repair, paracrine effects, and the promotion of angiogenesis, immune regulation, and anti-inflammatory effects. We also summarize current SC engineering strategies aimed at enhancing the immunosuppressive and regenerative capabilities of SCs for treating intestinal diseases. Additionally, we highlight current limitations and future perspectives of SC-related therapy for IBD.

Optimal Timing of Simethicone Supplement for Bowel Preparation: A Prospective Randomized Controlled Trial.

Background and Aims: Simethicone (SIM), as an antifoaming agent, has been shown to improve bowel preparation during colonoscopy. However, the optimal timing of SIM addition remained undetermined. We aimed to investigate the optimal timing of SIM addition to polyethylene glycol (PEG) to improve bowel preparation. Methods: Eligible patients were randomly assigned to two groups: the SIM evening group (SIM addition to PEG in the evening of the day prior to colonoscopy) and the SIM morning group (SIM addition to PEG in the morning of colonoscopy). The primary outcome was Bubble Scale (BS). The secondary outcomes were Boston Bowel Preparation Scale (BBPS) and adenoma detection rate (ADR). Results: A total of 419 patients were enrolled in this study. The baseline characteristics of the patients were similar in both groups. No significant differences were observed in terms of BS (8.76 ± 0.90 vs. 8.65 ± 1.16, P = 0.81), ADR (34.1% vs. 30.8%, P = 0.47), Boston Bowel Preparation Scale (BBPS) (8.59 ± 0.94 vs. 8.45 ± 1.00, P = 0.15), and withdrawal time (8.22 ± 2.04 vs. 8.01 ± 2.51, P = 0.094) between the two groups. Moreover, safety and compliance were similar in both groups. However, the SIM evening group was associated with shorter cecal intubation time (3.80 ± 1.81 vs. 4.42 ± 2.03, P < 0.001), higher BS (2.95 ± 0.26 vs. 2.88 ± 0.38, P = 0.04) in the right colon, and diminutive ADR (62.5% vs. 38.6%, P = 0.022) in the right colon, when compared to the SIM evening group. Conclusions: The SIM addition to PEG in the evening of the day prior to colonoscopy can shorten cecal intubation time and improve BS scores and diminutive ADR of the right colon compared with the SIM addition to PEG in the morning of colonoscopy in bowel preparation.

Comprehensive analysis on the expression profile and prognostic values of Synaptotagmins (SYTs) family members and their methylation levels in gastric cancer.

Synaptotagmins (SYTs), constitute a family of 17 membrane-trafficking protein, palying crucial roles in the development and progression of human cancers. However, only very few studies have investigated the expression profile and prognostic values of SYTs family members in gastric cancer (GC). Therefore, we comprehensively evaluated the expression, methylation, prognosis and immune significance of SYTs family members through bioinformatics analysis from the online databases in GC. The expressions of SYT4, SYT9, and SYT14 were up-regulated, and negatively associated with their methylation levels in GC. Both the over-expression of SYT4, SYT9 and SYT14 and their hypomethylation levels contributed to an unsatisfactory overall survival (OS) and progression-free survival (PFS) in GC. Moreover, the low expressions of several methylation cg sites (cg02795029, cg07581146, cg15149095, cg19922137, cg25371503, cg26158959, cg02269161, cg03226737, cg08185661, cg16437728, cg22723056 and cg24678137) were significantly correlated with an unfavorable OS and PFS in GC. Furthermore, the expression of SYT4, SYT9 and SYT14 played a pivotal role in immune cells infiltration in GC. Collectively, our current finding suggested that SYT4, SYT9 and SYT14 might be potent prognostic indictors and promising immunotherapeutic targets for GC patients.

Metabolic Reprogramming in Gastric Cancer: Trojan Horse Effect.

Worldwide, gastric cancer (GC) represents the fifth most common cancer for incidence and the third leading cause of death in developed countries. Despite the development of combination chemotherapies, the survival rates of GC patients remain unsatisfactory. The reprogramming of energy metabolism is a hallmark of cancer, especially increased dependence on aerobic glycolysis. In the present review, we summarized current evidence on how metabolic reprogramming in GC targets the tumor microenvironment, modulates metabolic networks and overcomes drug resistance. Preclinical and clinical studies on the combination of metabolic reprogramming targeted agents and conventional chemotherapeutics or molecularly targeted treatments [including vascular endothelial growth factor receptor (VEGFR) and HER2] and the value of biomarkers are examined. This deeper understanding of the molecular mechanisms underlying successful pharmacological combinations is crucial in finding the best-personalized treatment regimens for cancer patients.

The efficacy and safety of underwater endoscopic mucosal resection for ≥10-mm colorectal polyps: systematic review and meta-analysis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) is a promising strategy for nonpedunculated colorectal polyp removal. However, the efficacy and safety of the technique for the treatment of ≥ 10-mm colorectal polyps remain unclear. We aimed to comprehensively assess the efficacy and safety of UEMR for polyps sized 10-19 mm and ≥ 20 mm. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for relevant articles from January 2012 to November 2019. Primary outcomes were the rates of adverse events and residual polyps. Secondary outcomes were the complete resection, en bloc resection, and R0 resection rates. RESULTS: 18 articles including 1142 polyps from 1093 patients met our inclusion criteria. The overall adverse event and residual polyp rates were slightly lower for UEMR when removing colorectal polyps of 10-19 mm vs. ≥ 20 mm (3.5 % vs. 4.3 % and 1.2 % vs. 2.6 %, respectively). The UEMR-related complete resection rate was slightly higher for colorectal polyps of 10-19 mm vs. ≥ 20 mm (97.9 % vs. 92.0 %). However, the en bloc and R0 resection rates were dramatically higher for UEMR removal of polyps of 10-19 mm vs. ≥ 20 mm (83.4 % vs. 36.1 % and 73.0 % vs. 40.0 %, respectively). In addition, univariate meta-regression revealed that polyp size was an independent predictor for complete resection rate (P = 0.03) and en bloc resection (P = 0.01). CONCLUSIONS: UEMR was an effective and safe technique for the removal of ≥ 10-mm nonpedunculated colorectal polyps. However, UEMR exhibited low en bloc and R0 resection rates for the treatment of ≥ 20-mm polyps.

Bioinformatic Analysis Suggests That Three Hub Genes May Be a Vital Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide due to its ineffective diagnosis and poor prognosis. It is essential to identify differentially expressed genes (DEGs) in PDAC to gain new insights into its underlying molecular mechanisms, as well as identify potential diagnostic and therapeutic targets. We screened 135 DEGs from the GSE15417, GSE16515, and GSE28735 PDAC and normal pancreatic tissue microarray data sets, and identified 16 DEGs that were correlated with PDAC prognosis through the Kaplan-Meier survival analysis and log-rank tests. The Cancer Genome Atlas and Oncomine databases validated the expression levels of 16 candidate genes (SLC6A14, GPRC5A, IFI27, ERP27, SDR16C5, SIDT2, TCN1, COL12A1, MMP1, CEACAM6, DKK1, ITGA2, KRT19, PLAU, ANO1, and GABRP). Weighted gene coexpression network analysis (WGCNA) and protein and protein interaction (PPI) analysis identified three hub genes-ERP27, ITGA2, and MMP1-that are likely important in PDAC prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that they were enriched in functions of extracellular matrix organization, extracellular structure organization, and positive regulation of cell migration. Taken together, we identified three pivotal genes for PDAC, which can improve our understanding of its pathogenesis, progression, and prognosis.

Factors associated with diagnostic accuracy, technical success and adverse events of endoscopic ultrasound-guided fine-needle biopsy: A systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is used to diagnose lesions within or adjacent to the digestive tract. However, there is no report on the overall diagnostic accuracy, technical success, and adverse events of FNB. The aims of this study were to conduct a systematic review and meta-analysis to comprehensively assess the diagnostic accuracy, technical success, and adverse events of FNB. METHODS: Pubmed, Embase, and Cochrane Library databases were searched for relevant articles published in English from January 1998 to May 2019 (No. CRD42019141647). Primary outcomes were EUS-FNB related diagnostic accuracy rate, technical success rate, and adverse event rate. RESULTS: A total of 51 articles including 5330 patients met our criteria. The overall EUS-FNB related diagnostic accuracy rate, technical success rate, and adverse event rate was 90.82% [95% confidence interval (CI) 88.69-92.76%], 99.71% [95% CI 99.35-99.93%], and 0.59% [95% CI 0.29-1.0%], respectively. Biopsy with 22G needle could increase the diagnostic accuracy rate and technical success rate to 92.17% [95% CI 89.32-94.61%] and 99.88% [95% CI 99.64-99.99%], respectively, and decrease the adverse event to 0.37% [95% CI 0.08-0.87%]. Moreover, it showed that 22G needle was an independent factor associated with a higher diagnostic accuracy rate and technical success rate and a lower adverse event rate (P = 0.04, P < 0.001, and P = 0.04, respectively) by univariate and multivariate meta-regression analyses. CONCLUSION: Endoscopic ultrasound-guided fine-needle biopsy is a feasible and safe procedure for lesions within or adjacent to the digestive tract. Biopsy using 22G needle could increase the diagnostic accuracy rate and technical success rate and decrease adverse event rate during the FNB procedure.

Comparative study of the transfection efficiency of commonly used viral vectors in rhesus monkey (Macaca mulatta) brains.

Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system. In brain research, a series of powerful and novel gene editing technologies are based on these systems. Although many viral vectors are used in rodents, their full application has been limited in non-human primates. To identify viral vectors that can stably and effectively express exogenous genes within non-human primates, eleven commonly used recombinant adeno-associated viral and lentiviral vectors, each carrying a gene to express green or red fluorescence, were injected into the parietal cortex of four rhesus monkeys. The expression of fluorescent cells was used to quantify transfection efficiency. Histological results revealed that recombinant adeno-associated viral vectors, especially the serotype 2/9 coupled with the cytomegalovirus, human synapsin I, or Ca2+/calmodulin-dependent protein kinase II promoters, and lentiviral vector coupled with the human ubiquitin C promoter, induced higher expression of fluorescent cells, representing high transfection efficiency. This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates (NHPs). These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.