Facilitating endoscopic full-thickness resection for gastric submucosal tumors with a novel snare traction method (with video).

BACKGROUND AND AIM: Endoscopic full-thickness resection (EFTR) is a promising technique in treating gastric submucosal tumors originating from the muscularis propria (SMT-MPs). However, it is challenging without counter-traction. METHODS: A snare was inserted through the forceps channel to grasp the part of the tumor or the mucosa connected to the tumor. The outer sheath and inner wire of snare in vitro were fixed by a pair of hemostatic forceps. The handle of snare was cut off, and the endoscope was pulled out without affecting the traction state of snare. Snare-assisted EFTR (EFTR-S) was then performed with counter-traction. One hundred and four patients with gastric SMT-MPs who received the procedure of EFTR with or without snare traction method were retrospectively analyzed using univariate and multiple regressions, and covariates were adjusted in the multiple analysis. RESULTS: Compared with EFTR group (n = 36), EFTR-S group (n = 68) showed a higher operative success rate (95.6% vs 72.2%, P = 0.001), a lower incidence of intraoperative hemorrhage (4.4% vs 16.7%, P = 0.038) and shorter operative time among operative successes (53.6 ± 16.6 min vs 67.7 ± 33.4 min, P < 0.001). Univariate logistic analysis showed that snare traction represented a significant factor, which could improve operative successful rate (odds ratio, 8.3; 95% confidence interval, 2.1 to 32.7; P = 0.002). Postoperative outcomes and adverse events among operative successes were similar between the two groups. CONCLUSIONS: This novel snare traction method may provide an effective counter-traction and reduce the difficulty of EFTR for gastric SMT-MPs.

Comparison of endoscopic full-thickness resection and ligation-assisted endoscopic full-thickness resection for small (≤ 1.5 cm) gastric subepithelial tumors originating from muscularis propria.

BACKGROUND: In the treatment of small gastric subepithelial tumors originating from muscularis propria (SET-MPs), endoscopic full-thickness resection (EFTR) has been an effective procedure and ligation-assisted EFTR (EFTR-L) seems a feasible and promising operation. We aimed to compare the therapeutic outcomes of EFTR-L and EFTR to evaluate effect and safety of either method in the treatment of small (≤ 1.5 cm) gastric SET-MPs. METHODS: Between January 2018 to May 2022, we retrospectively enrolled a total of 119 patients with gastric SET-MPs treated by EFTR-L (79 patients) or EFTR (40 patients) at Xiangya Hospital Central South University. Clinical characteristics, operation efficacy, adverse events (AEs), and operation cost were compared between the 2 groups. Univariate and multiple logistic and linear regressions were applied to analyze the therapeutic outcomes of the procedure, and covariates were adjusted in the multiple analysis. RESULTS: The operation time of EFTR-L group (16.34 ± 5.75 min) was significantly shorter than EFTR group (51.23 ± 21.21 min, P < 0.001), and the difference remained significant after adjusting the covariates (adjusted mean difference, 30.56; 95% confidence interval, 25.65-35.47; P < 0.001). The operation cost of EFTR-L group was lower than EFTR group (1268.52 ± 457.22 vs 1643.18 ± 295.08 $; P < 0.001). The complete resection rate of the EFTR-L group was 98.72% and of the EFTR group 100%. The incidence of abdominal pain in the EFTR-L group (5.06%) was lower than in the EFTR group (27.50%, P = 0.008). A patient in the EFTR group underwent severe pneumoperitoneum and received abdominocentesis during operation. One case of peritonitis occurred in the EFTR-L group but recovered from intensified antibiotic therapy. No delayed blood or perforation occurred. CONCLUSIONS: Compared to EFTR, EFTR-L might be a feasible procedure for small (≤ 1.5 cm) gastric SET-MPs due to the acceptable efficacy, shorter operation time, and lower cost.

MicroRNA-182-5p aggravates ulcerative colitis by inactivating the Wnt/ß-catenin signaling pathway through DNMT3A-mediated SMARCA5 methylation.

This research focused on novel molecular mechanisms underlying microRNA (miR)-182-5p in ulcerative colitis (UC). Colon tissues were obtained from UC patients, and dextrose sodium sulfate (DSS)-induced mouse and interleukin-1ß (IL-1ß)-induced Caco-2 cell models were generated. Then, miR-182-5p, SMARCA5, and the Wnt/ß-catenin signaling pathway were altered in IL-1ß-stimulated Caco-2 cells and DSS-treated mice to assess their function. MiR-182-5p and SMARCA5 were upregulated and DNMT3A, ß-catenin, and Cyclin D1 were downregulated in UC patients, IL-1ß-stimulated Caco-2 cells, and DSS-treated mice. Mechanistically, miR-182-5p targeted DNMT3A to upregulate SMARCA5, thus blocking the Wnt/ß-catenin signaling pathway. Moreover, SMARCA5 silencing or Wnt/ß-catenin signaling pathway activation repressed apoptosis and augmented proliferation and epithelial barrier function of IL-1ß-stimulated Caco-2 cells. SMARCA5 silencing annulled the impacts of miR-182-5p overexpression on IL-1ß-stimulated Caco-2 cells. SMARCA5 silencing or miR-182-5p inhibition ameliorated intestinal barrier dysfunction in DSS-treated mice. Collectively, miR-182-5p aggravates UC by inactivating the Wnt/ß-catenin signaling pathway through DNMT3A-mediated SMARCA5 methylation.

Construction of Two Stable Co(II)-Based Hydrogen-Bonded Organic Frameworks as a Luminescent Probe for Recognition of Fe3+ and Cr2O72- in H2O.

A pair of cobalt(II)-based hydrogen-bonded organic frameworks (HOFs), [Co(pca)2(bmimb)]n (1) and [Co2(pca)4(bimb)2] (2), where Hpca = p-chlorobenzoic acid, bmimb = 1,3-bis((2-methylimidazol-1-yl)methyl)benzene, and bimb = 1,4-bis(imidazol-1-ylmethyl)benzene were hydrothermally synthesized and characterized through infrared spectroscopy (IR), elemental and thermal analysis (EA), power X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD) analyses. X-ray diffraction structural analysis revealed that 1 has a one-dimensional (1D) infinite chain network through the deprotonated pca- monodentate chelation and with a µ2-bmimb bridge Co(II) atom, and 2 is a binuclear Co(II) complex construction with a pair of symmetry-related pca- and bimb ligands. For both 1 and 2, each cobalt atom has four coordinated twisted tetrahedral configurations with a N2O2 donor set. Then, 1 and 2 are further extended into three-dimensional (3D) or two-dimensional (2D) hydrogen-bonded organic frameworks through C-H···Cl interactions. Topologically, HOFs 1 and 2 can be simplified as a 4-connected qtz topology with a Schläfli symbol {64·82} and a 4-connected sql topology with a Schläfli symbol {44·62}, respectively. The fluorescent sensing application of 1 was investigated; 1 exhibits high sensitivity recognition for Fe3+ (Ksv: 10970 M-1 and detection limit: 19 µM) and Cr2O72- (Ksv: 12960 M-1 and detection limit: 20 µM). This work provides a feasible detection platform of HOFs for highly sensitive discrimination of Fe3+ and Cr2O72- in aqueous media.

Silencing of RHEB inhibits cell proliferation and promotes apoptosis in colorectal cancer cells via inhibition of the mTOR signaling pathway.

Colorectal cancer (CRC) is commonly known as one of the most prominent reasons for cancer-related death in China. Ras homolog enriched in brain (RHEB) and the mammalian target activity of rapamycin (mTOR) signaling pathway were found correlated with CRC, but their specific interaction in CRC was still to be investigated. Therefore, we explored whether RHEB gene silencing affected the cell proliferation, differentiation, and apoptosis by directly targeting the mTOR signaling pathway in cells previously harvested from CRC patients. A microarray analysis was subsequently conducted to investigate the relationship between RHEB and mTOR. Eighty-three adjacent normal tissues and CRC tissues were selected. Immunohistochemistry was carried out to detect the positive expression rates of RHEB and Ki-67 in the CRC tissues. Cells were then transfected with different siRNAs to investigate the potential effects RHEB would have on CRC progression. The expressions of RHEB, 4EBP1, ribosomal protein S6 kinase (p70S6K), proliferating cell nuclear antigen (PCNA), B cell lymphoma 2 (bcl-2), and bcl-2-associated X protein (bax) were determined and then the cell cycle, cell proliferation, and apoptotic rate were also measured. We identified RHEB and mTOR as upregulated genes in CRC. Cells treated with RHEB silencing showed a decreased extent of mTOR, p70S6K, 4EBP1 phosphorylation and expression of RHEB, Ki-67, mTOR, p70S6K, 4EBP1, bcl-2, and PCNA as well as decreased activity of cell proliferation and differentiation; although, the expression of bax was evidently higher. Collectively, our data propose the idea that RHEB gene silencing might repress cell proliferation and differentiation while accelerating apoptosis via inactivating the mTOR signaling pathway.

microRNA-16-5p-containing exosomes derived from bone marrow-derived mesenchymal stem cells inhibit proliferation, migration, and invasion, while promoting apoptosis of colorectal cancer cells by downregulating ITGA2.

Colorectal cancer (CRC) is a form of cancer developing from either the colon or rectum. Nowadays, research supports the functionality of exosome expressing microRNAs (miRNAs) as potential biomarker for various cancers including CRC. This study was performed with the intent of investigating the roles of both bone marrow-derived mesenchymal stem cells (BMSCs) and exosomal miR-16-5p in CRC by regulating integrin α2 (ITGA2). A microarray-based analysis was conducted to screen the CRC-associated differentially expressed genes (DEGs) as well as potential regulatory miRNAs. Next, the role of miR-16-5p in terms of its progression in association with CRC was determined. Subsequently, CRC cells were exposed to exosomes secreted by BMSCs transfected with miR-16-5p, isolated and cocultured with CRC cells in an attempt to identify the role of exosomes. Effects of BMSCs-derived exosomes overexpressing miR-16-5p on biological functions of CRC cells and tumorigenicity were all subsequently detected. Effects of miR-16-5p treated with CRC cells in regard to CRC in vivo were also measured. ITGA2 was overexpressed, while miR-16-5p was poorly expressed in CRC cells and miR-16-5p targeted ITGA2. The in vitro experiments revealed that the BMSCs-derived exosomes overexpressing miR-16-5p inhibited proliferation, migration, and invasion, while simultaneously stimulating the apoptosis of the CRC cells via downregulation of ITGA2. Furthermore, the results of in vivo experiments confirmed that the BMSCs-derived exosomes overexpressing miR-16-5p repressed the tumor growth of CRC. Collectively, BMSCs-derived exosomes overexpressing miR-16-5p restricted the progression of CRC by downregulating ITGA2.

MiR-29a inhibited intestinal epithelial cells autophagy partly by decreasing ATG9A in ulcerative colitis.

Ulcerative colitis (UC), with high morbidity has become one of the fastest-growing severe illnesses in the world. Although MiR-29a is highly expressed in the tissues of UC patients, the mechanism of miR-29a involved in the specific pathogenesis of UC is not known. In this study, a GFP-light chain 3 (LC3) immunofluorescence assay was used to observe the formation of the autophagic spot; qRT-PCR and western blotting analyses were carried out to detect the expression of autophagy-related proteins, including BECN1, Autophagy-related gene (ATG)5, ATG16L, and transcription factor EB. The dual-fluorescence reporter assay was used to analyze the direct effect of miR-29a on ATG9A; experimental dextran sulfate sodium-induced colitis in mice was used to establish the UC model. Our studies showed that the overexpression of miR-29a not only suppressed the production of GFP-LC3 autophagy spots but also inhibited the level of LC3II/LC3I and upregulated the expression of P62 in HT29 and HCT116 cells. Moreover, the results showed that miR-29a directly targeted the 3'UTR region of ATG9A mRNA to suppress the activation of HT29 and HCT116 cells' autophagy. Also, overexpression of ATG9A rescued rapamycin-induced autophagy that was inhibited by overexpression of miR-29a. In addition, miR-29a also affected the expression of autophagy-related proteins (BECN1, ATG5, ATG16L1, and transcription factor EB). Notably, miR-29a was upregulated, whereas ATG9A was downregulated in the experimental dextran sulfate sodium-induced colitis in mice. In effect, this study showed that miR-29a inhibits rapamycin-induced intestinal epithelial cells' autophagy partly by decreasing ATG9A in UC. These findings may provide new insights that may help control the inflammation in UC.

[Option for different surgeries in treating small gastrointestinal stromal tumors].

OBJECTIVE: To explore the differences in biological characteristics for the small gastrointestinal stromal tumors and the incidence of complications and recurrence between the traditional surgical treatment and endoscopic treatment.
 Methods: We collected the relevant clinical and pathological data from patients who were diagnosed as gastrointestinal stromal tumors with the diameter less than 2 cm by the Department of Pathology of Xiangya Hospital from January 2009 to December 2015. The complications and recurrence after the surgical treatment were analyzed.
 Results: In patients with small gastrointestinal stromal tumors, the proportion of female was higher than that of male (male:female=1:1.69). The median age for patient with this disease was 49 years old and it was more common in middle-aged and elderly. Most lesions were found in the stomach, followed by the esophagus and the small intestine. The small gastrointestinal stromal tumors occurred in the colon and rectum were rare. There was 60.3% (47/78) patients with abdominal pain, 7.7% (6/78) patients with hematochezia or melena, and 98.7% (78/79) with small gastrointestinal stromal tumors' mitotic count ≤5/50 HPF. The positive rates for CD, CD34, DOG-1, actin-smooth, and S-100 were 98.7%, 86.1%, 82.3%, 31.6%, and 24.1%, respectively. Three patients occurred surgical complications, 2 suffered recurrence during the follow-up. There was no significant difference in the incidence of complications and recurrence between the traditional surgical treatment and endoscopic treatment (P>0.05).
 Conclusion: Small gastrointestinal stromal tumors' malignant potential is low, and the recurrence and metastasis rate is low. Its biological behavior tends to be benign. The traditional surgical treatment and endoscopic treatment are both safe and effective for small gastrointestinal stromal tumor. Endoscopic treatment has the advantages in lower cost, shorter hospitalization time, and small trauma. Therefore, endoscopic treatment could be the first choice for small GIST resection under the condition of mature endoscopic technology.

Ionic-liquid-modified magnetic nanoparticles as a solid-phase extraction adsorbent coupled with high-performance liquid chromatography for the determination of linear alkylbenzene sulfonates in water samples.

Novel ionic-liquid-functionalized Fe3 O4 magnetic nanoparticles were synthesized by the thiol-ene click reaction. The prepared functionalized Fe3 O4 nanoparticles possessed multiple interactions, such as electrostatic, hydrophobic, and π-π interactions. The functionalized Fe3 O4 nanoparticles were characterized by using Fourier transform infrared spectroscopy, X-ray diffraction, vibrating sample magnetometry, and transmission electron microscopy. Four kinds of linear alkylbenzene sulfonates, namely, sodium decylbenzenesulfonate, sodium undecylbenzene sulfonate, sodium dodecylbenzenesulfonate, and sodium tridecylbenzenesulfonate, were selected as model compounds to evaluate the applicability of adsorbents for extraction and subjected to high-performance liquid chromatography analysis. In addition, the effects of various parameters, such as sorbent amount, pH value, ionic strength, sample volume, extraction time, and elution conditions on extraction efficiency were studied in detail. Under the optimum conditions, good linearities were attained, with correlation coefficients between 0.9912 and 0.9968. The proposed method exhibited limits of detection ranging from 0.061 to 0.099 µg/L for all the target analytes. The spiked recoveries of the target analytes in real water samples ranged from 86.3 to 107.5%, with relative standard deviations lower than 7.96%. The enrichment factors of the analytes ranged from 364 to 391, indicating that the obtained functionalized Fe3 O4 nanoparticles can effectively extract trace target analytes from environmental water samples.

Modulation by miR-29b of intestinal epithelium homoeostasis through the repression of menin translation.

Menin regulates distinct cellular functions by regulating gene transcription through its interaction with partner transcription factors, but the exact mechanisms that control menin levels remain largely unknown. In the present study we report that Men1 mRNA, encoding menin, is a novel target of miR-29b and that miR-29b/Men1 mRNA association regulates menin expression post-transcriptionally in rat intestinal epithelial cells (IECs). Overexpression of a miR-29b precursor lowered the levels of Men1 mRNA modestly, but reduced new synthesis of menin robustly; conversely, antagonism of miR-29b enhanced menin protein synthesis and steady-state levels. The repressive effect of miR-29b on menin expression was mediated through a single binding site in the coding region of Men1 mRNA, because point mutation of this site prevented miR-29b-induced repression of menin translation. Increasing cellular polyamines due to overexpression of ornithine decarboxylase (ODC) enhanced menin translation by reducing miR-29b, whereas polyamine depletion by inhibiting ODC increased it, thus suppressing menin expression. Moreover, an increase in menin abundance in an miR-29b-silenced population of IECs led to increased sensitivity to apoptosis, which was prevented by silencing menin. These findings indicate that miR-29b represses translation of Men1 mRNA, in turn affecting intestinal epithelial homoeostasis by altering IEC apoptosis.

Dynamic analysis of a fuzzy Bobwhite quail population model under g-division law.

This paper is concerned with a kind of Bobwhite quail population model x n + 1 = A + B x n + x n x n - 1 x n - 2 , n = 0 , 1 , ⋯ , where the parameters and initial values are positive parabolic fuzzy numbers. According to g-division of fuzzy sets and based on the symmetrical parabolic fuzzy numbers, the conditional stability of this model is proved. Besides the existence, boundedness and persistence of its unique positive fuzzy solution. When some fuzzy stability conditions are satisfied, the model evolution exhibits oscillations with return to a fixed fuzzy equilibrium no matter what the initial value is. This phenomena provided a vivid counterexample to Allee effect in density-dependent populations of organisms. As a supplement, two numerical examples with data-table are interspersed to illustrate the effectiveness. Our findings have been verified precise with collected northern bobwhite data in Texas, and will help to form some efficient density estimates for wildlife populations of universal applications.

Adverse events of biologic or small molecule therapies in clinical trials for inflammatory bowel disease: A systematic review and meta-analysis.

Background: Biologic or small-molecule therapies are highly effective for the treatment of inflammatory bowel disease (IBD), and approval by the FDA has significantly increased both their clinical use and the development of novel regimens. However, the identification and management of their associated toxicities poses challenges for clinicians and researchers. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) published from January 1, 2000, to October 15, 2022, and in the databases. A random-effects model with logit transformation was applied to the analysis heterogeneity between studies was evaluated using the I2 statistic with incidence and 95 % confidence interval (CI) for any adverse events (AEs), and serious AEs (SAEs). Results: In Crohn's disease (CD), the total AE incidence was 67.0 % (95 % CI, 66.2%-67.8 %; I2 = 97.2 %) for any AEs and 7.3 % (6.9-7.7; 97.2) for serious AEs. In ulcerative colitis (UC), the overall incidence of any and serious AEs was 63.6 % (63.0-64.3; 98.1) and 5.7 % (5.4-6.0; 88.9), respectively. The most common AEs were infections (21.5 [20.3-22.8], 32.6 [31.0-34.2], 25.9 [24.5-27.2], and 13.7 [10.7-16.7]) in CD patients that were treated with TNF antagonists, anti-integrins, anti-IL agents, and JAK inhibitors, respectively, and in UC patients also were infections (22.8 [21.7-24.0], 27.4 [25.9-28.9], and 18.4 [16.7-20.2]), respectively, as well as increases in lactic dehydrogenase levels (23.1 [20.8-25.4]) with JAK inhibitors. Conclusion: This study offers a comprehensive summary of toxic side effects of IBD treatments and a useful reference for both patients and clinicians.

E3 ubiquitin ligase RNF180 mediates the ALKBH5/SMARCA5 axis to promote colon inflammation and Th17/Treg imbalance in ulcerative colitis mice.

SMARCA5, a protein in the SWI/SNF family, has been previously implicated in the development of ulcerative colitis (UC) through methylation. However, the specific molecular mechanisms by which SMARCA5 contributes to colonic inflammation and the imbalance between Th17 and Treg cells remain unclear. This study was designed to explore these molecular mechanisms. A UC mouse model was established using dextran sulfate sodium induction, followed by measurements of mouse weight, disease activity index (DAI) score, colon length, pathological changes in the colon, and FITC-dextran concentration. The levels of IL-17a, IFN-γ, IL-6, TNF-α, TGF-ß, and IL-10 were measured, along with the protein expression of ZO-1 and Occludin. Flow cytometry was used to assess the presence of IL-17 + CD4 + (Th17 +) cells and FOXP3 + CD25 + CD4 + (Treg +) cells in the spleen and mesenteric lymph nodes of UC mice. We observed that SMARCA5 and RNF180 were increased, while ALKBH5 was downregulated in UC mouse colon tissue. SMARCA5 or RNF180 knockdown or ALKBH5 overexpression ameliorated the colon inflammation and Th17/Treg cell imbalance in UC mice, shown by increased body weight, colon length, FOXP3 + CD25 + CD4 + T cells, and the levels of ZO-1, Occludin, TGF-ß, IL-10, and FOXP3. It decreased DAI scores, IL-17 + CD4 + T cells, and levels of IL-17a, IFN-γ, IL-6, TNF-α, and ROR-γt. ALKBH5 inhibited SMARCA5 expression via m6A modification, while RNF180 reduced ALKBH5 expression via ubiquitination. Our findings indicate that RNF180 aggravated the colon inflammation and Th17/Treg cell imbalance in UC mice by regulating the ALKBH5/SMARCA5 axis.

CRISPR-based functional genomics screening in human-pluripotent-stem-cell-derived cell types.

While our knowledge of gene expression in different human cell types is rapidly expanding with advances in transcriptomic profiling technologies, the next challenge is to understand gene function in each cell type. CRISPR-Cas9-based functional genomics screening offers a powerful approach to determine gene function in a high-throughput manner. With the maturation of stem cell technology, a variety of human cell types can be derived from human pluripotent stem cells (hPSCs). Recently, the integration of CRISPR screening with hPSC differentiation technologies opens up unprecedented opportunities to systematically examine gene function in different human cell types and identify mechanisms and therapeutic targets for human diseases. This review highlights recent progress in the development and applications of CRISPR-Cas9-based functional genomics screening in hPSC-derived cell types, discusses current challenges and limitations, and outlines future directions for this emerging field.

Polyamines inhibit the assembly of stress granules in normal intestinal epithelial cells regulating apoptosis.

Polyamines regulate multiple signaling pathways and are implicated in many aspects of cellular functions, but the exact molecular processes governed by polyamines remain largely unknown. In response to environmental stress, repression of translation is associated with the assembly of stress granules (SGs) that contain a fraction of arrested mRNAs and are thought to function as mRNA storage. Here we show that polyamines modulate the assembly of SGs in normal intestinal epithelial cells (IECs) and that induced SGs following polyamine depletion are implicated in the protection of IECs against apoptosis. Increasing the levels of cellular polyamines by ectopic overexpression of the ornithine decarboxylase gene decreased cytoplasmic levels of SG-signature constituent proteins eukaryotic initiation factor 3b and T-cell intracellular antigen-1 (TIA-1)-related protein and repressed the assembly of SGs induced by exposure to arsenite-induced oxidative stress. In contrast, depletion of cellular polyamines by inhibiting ornithine decarboxylase with α-difluoromethylornithine increased cytoplasmic eukaryotic initiation factor 3b and TIA-1 related protein abundance and enhanced arsenite-induced SG assembly. Polyamine-deficient cells also exhibited an increase in resistance to tumor necrosis factor-α/cycloheximide-induced apoptosis, which was prevented by inhibiting SG formation with silencing SG resident proteins Sort1 and TIA-1. These results indicate that the elevation of cellular polyamines represses the assembly of SGs in normal IECs and that increased SGs in polyamine-deficient cells are crucial for increased resistance to apoptosis.

6-Chloro-2-phenyl-3-(2-phenyl-ethyn-yl)quinoxaline.

In the title compound, C(22)H(13)ClN(2), the quinoxaline ring system is close to planar [maximum deviation = 0.061 (2) Å]. The phenyl ring at the 2-position and the phenyl ring of the phenyl-ethynyl substituent make dihedral angles of 49.32 (7) and 11.99 (7) °, respectively, with the quinoxaline mean plane. The two phenyl rings are inclined to one another by 61.27 (9)°. In the crystal, mol-ecules are linked by C-H⋯π and π-π inter-actions [centroid-centroid distances = 3.6210 (12) and 3.8091 (12) Å].

Maternal diets have effects on intestinal mucosal flora and susceptibility to colitis of offspring mice during early life.

OBJECTIVES: Intestinal flora is considered closely related to the occurrence of inflammatory bowel disease (IBD). This study aimed to discover whether diverse diet conditions during early life lead to different intestinal flora structure and impact different susceptibility to IBD. METHODS: We performed a randomized, controlled trial to investigate the relationship between maternal diet, intestinal flora, and susceptibility of IBD in offspring mice. We treated the maternal mice with different dietary conditions (maternal high fat, high protein, or normal diet, and offspring continued maternal diets or changed to normal diet), and then extracted bacterial meta-genomic DNA from the intestinal mucosa of the offspring during the early life and adult stages. We amplified and sequenced the conserved gene v3-v4 of the bacterial 16 S ribosomal RNA. After dextran sulphate sodium intervention, we evaluated the susceptibility to intestinal inflammation with hematoxylin and eosin stains and disease activity index scores. RESULTS: The number of species and alpha diversity of weaning mice (3 wk old) fed a maternal high-protein diet were significantly lower than those of the control diet group (P < 0.05). Among adult (8 wk old) offspring rats, the alpha diversity of mice that continued on a high-protein diet remained significantly decreased (P < 0.05). In addition, 12 kinds of weak bacteria were found in weaning mice fed a maternal high-protein diet compared with the control group. Offspring that continued in the maternal high-protein group had increased disease activity index and pathologic scores after weaning. CONCLUSIONS: In general, our study shows that a maternal high-protein diet during early life can negatively regulate the intestinal flora diversity of offspring mice. A high-protein diet during early life led to higher susceptibility of IBD in offspring rats.

Circular RNA HECTD1 Mitigates Ulcerative Colitis by Promoting Enterocyte Autophagy Via miR-182-5p/HuR Axis.

OBJECTIVE: Ulcerative colitis (UC) is a chronic colitis with unknown etiology. Circular RNA (circRNA) has shown regulatory effect in many diseases, but the role of circRNA in UC is barely known. This study uncovers the function and regulatory mechanism of circRNA HECTD1 (circHECTD1) in UC. METHODS: Colonic mucosal tissues of 60 patients with active UC and 30 healthy controls were collected for H&E staining. Lipopolysaccharide (LPS) and dextran sulfate sodium (DSS) were used to induce inflammation and UC in Caco-2 cells and C57BL/6 mice where modification of circHECTD1, miR-182-5p and/or human antigen R (HuR) took place. The Caco-2 cells and the colon tissues of DSS-treated mice were collected for analysis of the expression levels of inflammatory cytokines, NLRP3 inflammasome, and autophagy-related proteins. The interactions among circHECTD1, miR-182-5p, and HuR were verified. RESULTS: The colonic mucosal tissues of UC patients showed impaired autophagy and decreased expressions of circHECTD1 and HuR. Overexpression of circHECTD1 or HuR or inhibition of miR-182-5p suppressed inflammation and promoted autophagy of LPS-induced Caco-2 cells. The expression of HuR was promoted by circHECTD1 via miR-182-5p in Caco-2 cells. Overexpression of circHECTD1 reduced colonic injuries and inflammation by promoting autophagy in DSS-treated mice. CONCLUSION: Overexpression of circHECTD1 alleviates UC by promoting HuR-dependent autophagy via miR-182-5p. This study highlights the therapeutic potential of circHECTD1 for UC and adds to the knowledge of circRNA in the pathogenesis of UC.