Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the ...psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washingprocess. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.
Abstract
The purpose of our study was to evaluate the effect of surgery on the survival and prognosis of patients with multifocal intrahepatic cholangiocarcinoma (ICCA). Patients with multifocal ICCA ...were selected from the SEER (Surveillance, Epidemiology, and End Results) database between 2010 and 2016. Kaplan–Meier analyses and log-rank tests were used to evaluate the difference in survival between the surgery group and the non-surgery group. We applied the Cox proportional hazards regression model to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). In total, 580 patients were enrolled in our study, including 151 patients who underwent surgery and 429 patients who did not. The median survival time of surgical patients was longer than non-surgical patients (OS: 25 months vs. 8 months, p < 0.001; CSS: 40 months vs. 25 months, p < 0.001). Similarly, the 5-year survival rate in the surgery group was significantly higher than those in the non-surgery group (5-year OS rate: 12.91% vs. 0%; p < 0.001; 5-year CSS rate:26.91% vs. 0%; p < 0.001). Multivariate Cox analysis showed that the OS (HR:0.299, 95% CI: 0.229–0.390, p < 0.001) and CSS (HR:0.305, 95% CI:0.222–0.419, p < 0.001) of patients undergoing surgical resection were significantly improved. Meanwhile, after propensity score matching (PSM) of the original data, we come to the same conclusion.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Akkermansia muciniphila
is a promising probiotic in the gut. This study aimed to determine the presence and abundance of
Akkermansia
in patients with inflammatory bowel disease (IBD) who underwent ...washed microbiota transplantation (WMT) in order to elucidate the relationship between its level and patients’ clinical data and outcomes. A cohort of Chinese volunteers including 80 healthy controls (HC), 43 patients with ulcerative colitis (UC), and 57 patients with Crohn’s disease (CD) were recruited.
Akkermansia
presented a low colonization rate of 48.8% and a relative abundance of 0.07% in a healthy Chinese population. Compared with HC, significantly lower colonization and abundance of
Akkermansia
were found in UC and CD (
p
< 0.01,
p
< 0.001, respectively). The combination of
Akkermansia
and twelve other gut commensal bacteria significantly enriched in healthy individuals could be conductive to discriminate IBD from HC. Co-occurrence of
Akkermansia
-
Faecalibacterium prausnitzii
was at a lower level in IBD. Patients’ age could affect the abundance of
Akkermansia
in CD. After WMT, 53.7% of patients achieved clinical response, and the colonization rate of
Akkermansia
increased significantly than that pre-WMT (
p
< 0.01). There was a positive correlation between patients and donors in the abundance of
Akkermansia
after WMT. Different from Europeans, the healthy Chinese population is characterized by a low presence of intestinal
Akkermansia
. Compared with healthy people, its colonization and abundance in IBD decreased more significantly. The efficacy of WMT for IBD was closely correlated with
Akkermansia
.
ClinicalTrials.gov
, pooled registered trials, NCT01790061, NCT01793831. Registered February 13, 2013, 18 February 2013.
Key points
•
Akkermansia showed a lower colonization and abundance in Chinese than Europeans.
• Akkermansia could distinguish IBD from healthy people with a reduced abundance.
• IBD patients achieved response from WMT through an increased Akkermansia level.
Graphical abstract
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CEKLJ, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The therapeutic role of fecal microbiota transplantation in ulcerative colitis varies across different reports. This study aims to evaluate the long-term safety and efficacy of a strategy called ...step-up fecal microbiota transplantation for ulcerative colitis.
Two clinical trials (NCT01790061, NCT02560727) for moderate-to-severe ulcerative colitis (Mayo score range 6-12) were performed from November 2012 to July 2017. Both studies were pooled for analysis on the safety and efficacy of fecal microbiota transplantation in patients with ulcerative colitis over a 1-year follow-up. The step-up fecal microbiota transplantation strategy included step 1: single fecal microbiota transplantation; step 2: two or more fecal microbiota transplantations; and step 3: fecal microbiota transplantations followed by immunosuppressants. Long-term clinical efficacy and adverse events were assessed, and multiple factors related to fecal microbiota transplantation were evaluated.
Of 134 eligible patients in this real-word study, 81.3% (109/134) were included for analysis. The follow-up ranged from 1 to 5 years. Fecal microbiota transplantation-related adverse events were observed in 17.4% (43/247) of fecal microbiota transplantation procedures including one serious adverse event (myasthenia gravis) and 56 non-serious adverse events. Multivariable logistic regression analysis showed that both the method of preparation of microbiota from stool using the automatic system and the delivery method of colonic transendoscopic enteral tubing were associated with a lower rate of fecal microbiota transplantation-related adverse events (p = 0.023, p = 0.017, respectively). In total, 74.3% (81/109) and 51.4% (56/109) of patients achieved clinical response at 1 month and 3 months after step-up fecal microbiota transplantation, respectively.
Fecal microbiota transplantation should be a safe and promising therapy for ulcerative colitis. The improved fecal microbiota preparation and colonic transendoscopic enteral tubing might reduce the rate of adverse events in ulcerative colitis.
ClinicalTrials.gov NCT01790061, NCT02560727.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Inflammatory bowel disease (IBD) is a significant health problem with an increasing financial burden worldwide. Although various treatment strategies have been used, the results were not ...satisfactory. More and more researches have proved that the application of phosphatidylcholine (PC) may become an alternative therapy for IBD.
This review aims to provide an overview of the possible mechanisms of PC and promote the potential application of PC for IBD therapy further.
A comprehensive literature search was performed in PubMed with the following keywords: 'phosphatidylcholine', 'inflammatory bowel disease', 'Crohn's disease', 'inflammation', 'ulcerative colitis', 'therapy', 'nanomedicines', 'PKCζ', 'lysophosphatidylcholine', 'microbiota' and 'drug carrier'. The logical operators "AND" and "OR" were applied to combine different sets of the search results.
Studies suggested that PC displays a significant effect in the treatment of IBD by modulating gut barrier function, remodeling gut microbiota structure, regulating polarization of macrophages, and reducing the inflammatory response. PC has also been exploited as a drug carrier for anticancer or anti-inflammation agents in multiple forms, which implies that PC has immense potential for IBD therapy.
PC has shown promising potential as a new therapeutic agent or a drug carrier, with a novel, stable, prolonged mechanism of action in treating IBD. However, more high-quality basic and clinical studies are needed to confirm this.
Abstact
Background and Aim
The gut microbiota plays a pivotal role in the intestinal diseases. Fecal microbiota transplantation (FMT) might be a rescue therapy for refractory inflammatory bowel ...disease. This study aimed to evaluate the safety, feasibility, and efficacy of FMT through mid‐gut for refractory Crohn's disease (CD).
Methods
We established standardized laboratory protocol and clinical work flow for FMT. Only refractory CD patients with Harvey–Bradshaw Index (HBI) score ≥ 7 were enrolled for this study. All included patients were treated with single FMT through mid‐gut and assessed during follow‐up.
Results
Metagenomics analysis showed a high concordance between feces sample and purified fecal microbiota from same donors. Standardized fecal microbiota preparation and clinical flow significantly simplified the practical aspects of FMT. Totally, 30 patients were qualified for the present analysis. The rate of clinical improvement and remission based on clinical activity at the first month was 86.7% (26/30) and 76.7% (23/30), respectively, which was higher than other assessment points within 15‐month follow‐up. Patients' body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD.
Conclusion
This is a pilot study with the largest sample of patients with refractory CD who underwent single FMT. The results demonstrated that FMT through mid‐gut might be a safe, feasible, and efficient rescue therapy for refractory CD.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal ...Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.
Background and aims
With the development of endoscopic technology, endoscopic treatment has been widely used in Gastrointestinal stromal tumors (GISTs). However, population-based studies comparing ...the long-term results of patients who received endoscopic treatment vs. Surgery are lacking. We used the Surveillance, Epidemiology, and End Results (SEER) database to analyze the long-term survival of colorectal or gastric GISTs who underwent primary tumor resection (endoscopic therapy or surgery) in the USA.
Methods
Patients with colorectal or gastric GISTs were selected from the SEER database between 2010 and 2015. Kaplan–Meier analyses and log-rank tests were used to evaluate the difference in the long-term survival between the endoscopic therapy group and the surgery group. We examined the association between different treatments and survival after using the multivariate cox proportional hazards model to adjust the relevant covariates. Besides, we used Propensity score matching (PSM) to overcome the different distributions of covariates between the two groups and then further compare the survival difference.
Results
In total, 2355 patients were enrolled in our study, of which 1999 (84.9%) received surgical treatment and 356 (15.1%) received endoscopic treatment. There was no significant difference in overall survival (OS) between the two groups before PSM. The median OS (73.5 months vs. 72.2 months) and 5-year OS rate (85.7% vs. 81.5%) of endoscopic therapy were similar to surgical patients (
P
= 0.34). The median Cancer-specific survival (CSS) and 5-year CSS rate in the endoscopic treatment group were higher than the surgical group before PSM, with 81.3 months, 97.1% versus 78.8 months, 92.7% (
P
= 0.011). After adjusting for other clinical factors and PSM, the long-term OS and CSS did not significantly differ between those treated surgically and treated endoscopically.
Conclusion
Based on the American population, we preliminarily found that the long-term OS and CSS did not differ between patients undergoing endoscopic therapy and surgery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and cancer progression. Recently, the lncRNA AGAP2-AS1 was identified as an oncogenic lncRNA in human non-small ...cell lung cancer (NSCLC) and its elevated expression was linked to NSCLC development and progression. However, the expression pattern and molecular mechanism of AGAP2-AS1 in gastric cancer (GC) have not been characterized.
Bioinformatic analysis was performed to determine AGAP2-AS1 expression levels in the GC and normal tissues using gene profiling data from the Gene Expression Omnibus. Quantitative real-time polymerase chain reaction was used to validate AGAP2-AS1 expression in the GC tissues/cell lines compared with that in the adjacent nontumorous tissues/normal epithelial cells. Loss- and gain-of-function approaches were performed to investigate the effect of AGAP2-AS1 on GC cell phenotypes. The effect of AGAP2-AS1 on cell proliferation was evaluated by MTT, colony formation, flow cytometry, and in vivo tumor formation assays. The effects of AGAP2-AS1 on cell migration and invasion were examined using Transwell assays. Chromatin immunoprecipitation, luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation were used to investigate the factors involved in AGAP2-AS1 dysregulation and the mechanism of action of AGAP2-AS1 in the GC cells.
AGAP2-AS1 was highly expressed in the GC tissues and cell lines, and patients with higher AGAP2-AS1 expression had a poorer prognosis and shorter overall survival. Furthermore, knockdown of AGAP2-AS1 significantly inhibited GC cell proliferation, migration, and invasion in vitro and tumor growth in vivo. AGAP2-AS1 overexpression promoted cell growth and invasion. In addition, the transcription factor SP1 activated AGAP2-AS1 expression in the GC cells. AGAP2-AS1 functions as an oncogenic lncRNA by interacting with LSD1 and EZH2 and suppressing CDKN1A (P21) and E-cadherin transcription.
Taken together, these findings imply that AGAP2-AS1 upregulated by SP1 plays an important role in GC development and progression by suppressing P21 and E-cadherin, which suggests that AGAP2-AS1 is a potential diagnostic marker and therapeutic target for GC patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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