ObjectivesSeveral reports suggesting that the intestinal microbiome plays a key role in the development of inflammatory bowel disease (IBD) or colorectal cancer (CRC), but the changes of intestinal bacteria in healthy people, patients with IBD and CRC are not fully explained. The study aimed to investigate changes of intestinal bacteria in healthy subjects, patients with IBD, and patients with CRC.MaterialsWe collected data from the European Nucleotide Archive on healthy people and patients with colorectal cancer with the study accession number PRJEB6070, PRJEB7774, PRJEB27928, PRJEB12449, and PRJEB10878, collected IBD patient data from the Integrated Human Microbiome Project from the Human Microbiome Project Data Portal. We performed metagenome-wide association studies on the fecal samples from 290 healthy subjects, 512 IBD patients, and 285 CRC patients. We used the metagenomics dataset to study bacterial community structure, relative abundance, functional prediction, differentially abundant bacteria, and co-occurrence networks.ResultsThe bacterial community structure in both IBD and CRC was significantly different from healthy subjects. Our results showed that IBD patients had low intestinal bacterial diversity and CRC patients had high intestinal bacterial diversity compared to healthy subjects. At the phylum level, the relative abundance of Firmicutes in IBD decreased significantly, while the relative abundance of Bacteroidetes increased significantly. At the genus level, the relative abundance of Bacteroides in IBD was higher than in healthy people and CRC. Compared with healthy people and CRC, the main difference of intestinal bacteria in IBD patients was Bacteroidetes, and compared with healthy people and IBD, the main difference of intestinal bacteria in CRC patients was in Fusobacteria, Verrucomicrobia, and Proteobacteria. The main differences in the functional composition of intestinal bacteria in healthy people, IBD and CRC patients were L-homoserine and L-methionine biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis II, L-methionine biosynthesis I, and superpathway of L-lysine, L-threonine, and L-methionine biosynthesis I. The results of stratified showed that the abundance of Firmicutes, Bacteroidetes, and Actinobacteria involved in metabolic pathways has significantly changed. Besides, the association network of intestinal bacteria in healthy people, IBD, and CRC patients has also changed.ConclusionsIn conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in IBD and CRC patients was significantly changed.
Retinoblastoma (RB) is a common neoplasm that is exhibited in individuals globally. Increasing evidence demonstrated that cyclin-dependent kinase regulatory subunit 1B (CKS1B) may be involved in the pathogenesis of various tumor types, including multiple myeloma and breast cancer. In the present study, the hypothesis that CKS1B down-regulation would effectively inhibit the proliferation, invasion and angiogenesis of RB cells through the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway was examined. Initial investigation of the expression profile of CKS1B in RB and adjacent retina tissues was performed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. A total of three RB cell lines, SO-RB50, Y79 and HXO-RB44, were examined for selection of the cell line with the highest expression of CKS1B, and human normal retinal vascular endothelial cells (ACBRI-181) were also evaluated. CKS1B short hairpin RNA (shRNA) sequences (shRNA CKS1B-1, shRNA CKS1B-2 and shRNA CKS1B-3) and negative control shRNA sequences were constructed and transfected into cells at the third generation to evaluate the role of shCKS1B and the MEK/ERK signaling pathway in RB. Furthermore, the effect of shCKS1B on cell proliferation, migration, invasion, apoptosis and angiogenesis was investigated. CKS1B was determined to be highly expressed in RB tissue, compared with adjacent retina tissue. SO-RB50 and HXO-RB44 cells treated with shRNA CKS1B-1 and shRNA CKS1B-2 were selected for the present experiments. Activation of the MEK/ERK signaling pathway increases the expression of MEK, ERK, B-cell lymphoma 2, proliferating cell nuclear antigen, cyclin D1, vascular endothelia growth factor and basic fibroblast growth factor, enhances cell proliferation, migration, invasion and lumen formation, and decreases apoptosis. Following silencing CKS1B, the aforementioned conditions were reversed. The key observations of the present study demonstrated that shCKS1B can inhibit the proliferation, invasion and angiogenesis of RB cells by suppressing the MEK/ERK signaling pathway. Thus, CKS1B represents a potential research target in the development of therapeutics for RB.
Using reverse transcription polymerase chain reaction, we cloned and sequenced full-length mouse cDNAs for the two homologous subunits of the proteasome activator PA28 (PA28alpha and PA28beta), as well as for the related protein Ki. These proteins are highly conserved among species. Northern blot analysis of PA28a, PA28b, and Ki mRNA demonstrated broad tissue distribution. Although single transcripts were detected for PA28a and PA28b, two different sized transcripts were detected for mouse Ki, suggesting either alternative splicing or alternate polyadenylation sites. The levels of these transcripts increased in response to interferon-gamma (IFN-gamma) treatment in mouse H6 hepatoma cells, although PA28a and PA28b were induced to a greater extent than Ki, and the effect of IFN-gamma stimulation on Ki expression was transient. Southern blot analysis suggests that both PA28a and PA28b are multiple-copy genes, while Ki is a single-copy gene.
Retinitis pigmentosa (RP) is a group of inherited diseases that primarily affect light‑sensitive rods and cones in the retina. Rhodopsin mutations, including the T17M mutation, are associated with the autosomal dominant form of retinitis pigmentosa (ADRP) and have been linked to abnormal protein folding. However, the molecular mechanisms underlying T17M rhodopsin‑induced retinal degeneration are yet to be elucidated. In the present study, Human embryonic kidney (HEK) 293 and ARPE‑19 cells were transfected with myc‑tagged wild‑type (WT) and T17M rhodopsin constructs. Cells were fixed and stained with anti‑myc antibodies and the localization of WT and T17M rhodopsin was visualized using immunofluorescence microscopy. Turnover rates of WT and T17M rhodopsin were measured using western blot analysis. In addition, endoplasmic reticulum (ER) stress‑induced cell death was analyzed in WT and T17M rhodopsin‑transfected cells using nuclear staining. Misfolded T17M rhodopsin was observed to be abnormally localized in the ER, while WT rhodopsin was predominantly found at the plasma membrane. Protein turnover analysis revealed that T17M rhodopsin was more rapidly degraded by proteasomes than WT rhodopsin. Furthermore, overexpression of T17M rhodopsin was observed to induce cell death and increase cytotoxicity; predisposing cells to ER stress‑induced cell death. These findings show novel insight into the properties of T17M rhodopsin and highlight the role of ER stress in T17M‑associated RP.
This study analyzed the optical coherence tomography angiography (OCTA) macular parameters in primary angle-closure glaucoma (PACG) patients after acute primary angle closure (APAC) episodes. Thirty-three patients with 33 APAC eyes and 33 primary angle closure suspect (PACS) eyes and 33 age-matched normal subjects (controls) were enrolled. Macular vessel density (VD) in central, inner, outer and full regions and foveal avascular zone (FAZ) parameters (area, perimeter and circularity index) were compared between APAC, PACS, and control eyes. For resolved APAC eyes, the VD in each macular region was significantly lower than that in control eyes, with less central and inner macular VD than PACS eyes. The central macular VD was significantly lower in PACS eyes than in controls. There was no difference in FAZ area and perimeter between APAC, PACS, and control eyes. FAZ circularity was highest in control eyes, followed by PACS eyes, and lowest in APAC eyes. The AUC, sensitivity and specificity of FAZ circularity were 0.944, 93.9% and 84.8%, respectively, in APAC eyes and 0.881, 84.8% and 81.8%, respectively, in PACS eyes. Therefore, FAZ circularity had the best discrimination capability for detecting both APAC and PACS eyes. Macular assessment with OCTA could provide an accurate early-stage diagnostic tool for PACG.
This study aimed to evaluate the efficacy of Ahmed glaucoma valve (AGV) implantation in treating neovascular glaucoma (NVG) and to analyze the factors influencing the surgical success rate.This is a retrospective review of 40 eyes of 40 NVG patients who underwent AGV implantation at Xiangya Hospital of Central South University, China, between January 2014 and December 2016. Pre- and postoperative intraocular pressure (IOP), visual acuity, surgical success rate, medications, and complications were observed. Surgical success criteria were defined as IOP ≤21 and >6 mm Hg with or without additional medications. Kaplan–Meier survival curves and Multivariate cox regression analysis were used to examine success rates and risk factors for surgical outcomes.The mean follow-up period was 8.88 ± 3.12 months (range: 3–17). IOP declined at each visit postoperatively and it was statistically significant (P < .001). An average of 3.55 ± 0.86 drugs was applied preoperatively, while an average of 0.64 ± 0.90 drugs was used postoperatively, with the difference being of statistical significance (P < .05). The complete surgical success rate of 3, 6, and 12 months after the operation was 85%, 75%, and 65%, respectively. Meanwhile, the qualified success rate of 3, 6, and 12 months after the operation was 85%, 80%, and 77.5%, respectively. The multivariate cox regression analysis showed that age (hazard ratio: 3.717, 7.246; 95% confidence interval: 1.149–12.048, 1.349–38.461; P = .028, .021) was influencing factors for complete success rate and qualified success rate among all NVG patients. Gender, previous operation history, primary disease, and preoperative IOP were found to be not significant.AGV implantation is an effective and safe surgical method to treat NVG. Age is an important factor influencing the surgical success rate.
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