Abstract Colorectal cancer (CRC) is a fatal disease ranking the third among the commonplace cancer types around the world. It is extremely significant to exploit effective treatments against CRC. FAM225A was proved to influence cell progression and forecast unfavorable prognosis in nasopharyngeal carcinoma. The role and function mechanism of FAM225A are still unclear in CRC. In this research, FAM225A was discovered presenting much higher expression in CRC tissues and cell lines. In addition, depleting FAM225A was capable of inhibiting cell proliferation, migration, and epithelial‐to‐mesenchymal transition (EMT) progress, and enhancing cell apoptosis ability. Furthermore, miR‐613 exerted important effects as a mediator between FAM225A and NOTCH3. NOTCH3 was negatively correlated with miR‐613, whereas was positively associated with FAM225A. Via competitively binding with miR‐613, FAM225A positively regulated NOTCH3 expression. FAM225A facilitated CRC occurrence and development through positively regulating NOTCH3 expression by binding with miR‐613. In a word, FAM225A/miR‐613/NOTCH3 axis may play a tumor‐facilitator in CRC cell progression. These data manifested the pivotal effect of FAM225A/miR‐613/NOTCH3 pathway in CRC cell proliferation, apoptosis, and migration process. The findings may provide some theoretical basis and different perspective for CRC treatment.
Objective: To investigate the effect and molecular mechanism of circular RNA-UBXN7 (circ_UBXN7) on the proliferation, migration and apoptosis of hepatocellular carcinoma cells. Methods: Circ_UBXN7 expression in the tissues and cells of hepatocellular cancer was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the relationship between circ_UBXN7 expression and clinicopathological features, including age, gender, tumor volume, pathological classification, staging, and lymph node metastasis was analyzed. The full-length sequence of circ_UBXN7 with lentivirus carrying lenti circ_UBXN7 and lenti circ_UBXN7 shRNA was constructed to transfect hepatocellular cell lines (HepG2 and Huh-7), respectively. CCK-8 experiments were performed to detect the ability of up- or down-regulation of circ_UBXN7 on the proliferation of HEPG2 and HUH-7 cells. Annexin V / PI experiment was used to detect the changes in apoptosis of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. JC-1 assay was used to detect the changes in mitochondrial potential energy of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. Transwell was used to detect the migration ability of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. Western blotting was used to detect the expressional change of TWIST, E-cadherin, N-cadherin and vimentin. Statistical analysis: The expression levels of circ_UBXN7 and clinicopathological features were measured by chi-square test. Two groups were compared by t-test and three groups and above were compared by single factor analysis of variance. LSD method was used for comparison between groups. Results: The expression of circ_UBXN7 in liver cancer tissues was significantly higher than adjacent tissues, and its expression level was significantly positively correlated with tumor volume, stage, and lymph node metastasis (P < 0.05). Lenti-circ_UBXN7 had up-regulated the expression of circ_UBXN7 in HEPG2 and HUH-7 cells and promoted cell proliferation. Lenti-circ_UBXN7-shRNA had down-regulated the expression of circ_UBXN7 and induced apoptosis. Lenti-circ_UBXN7-shRNA had reduced the mitochondrial membrane potential of cells. Lenti-circ_UBXN7 had promoted cell migration, while lenti-circ_UBXN7-shRNA had inhibited cell migration. Lenti-circ_UBXN7 had induced increased expression of Twist, N-cadherin, and Vimentin proteins, and reduced the expression of E-cadherin protein. Lenti-circ_UBXN7-shRNA had opposite effects on the expression levels of each protein. Starbase V2.0 software showed that miR-203a and circ_UBXN7 had potential binding sites, and miR-203a and circ_UBXN7 expression levels were negatively correlated in HEP G2 and HUH-7 cells. Conclusion: circ_UBXN7 plays an important role in promoting the occurrence and development of liver cancer, and is expected to become a potential target for the treatment of liver cancer.目的： 探讨环状RNA-UBXN7（circ_UBXN7）对肝癌细胞增殖、迁移以及凋亡的影响，并初步探讨其中的分子机制。 方法： 采用qRT-PCR检测circ_UBXN7在肝癌组织和细胞中的表达水平，并分析circ_UBXN7与患者临床病理因素如年龄、性别、肿瘤体积、病理分型、分期、淋巴结转移之间的相关性。构建携带circ_UBXN7全长序列的慢病毒（Lenti-circ_UBXN7）和携带circ_UBXN7 shRNA的慢病毒（Lenti-circ_UBXN7-shRNA）分别转染肝癌细胞株（HepG2和HUH-7）。CCK-8实验检测circ_UBXN7表达上调或下调后对HepG2和HUH-7细胞的增殖能力的影响。Annexin V/PI实验检测circ_UBXN7表达上调或下调后HepG2和HUH-7细胞的凋亡变化。JC-1法检测circ_UBXN7表达上调或下调后HepG2和HUH-7细胞线粒体势能的变化。Transwell检测circ_UBXN7表达上调或下调后HepG2和HUH-7细胞迁移能力变化。蛋白质印迹法检测细胞上皮间质化标志蛋白TWIST、E-钙黏蛋白（E-cadherin）、N-cadherin、Vimentin的表达变化。circ_UBXN7表达水平与临床病理因素采用χ(2)检验，两组比较采用t检验，三组及以上比较采用单因素方差分析且组间比较采用LSD法。 结果： circ_UBXN7在肝癌组织中表达显著高于癌旁组织，且其表达水平与肿瘤体积、分期和淋巴结转移显著正相关（P < 0.05）。Lenti-circ_UBXN7可以上调HepG2和HUH-7细胞内circ_UBXN7表达并促进细胞增殖；Lenti-circ_UBXN7-shRNA可以下调circ_UBXN7表达并诱导细胞凋亡。Lenti-circ_UBXN7-shRNA可以导致细胞线粒体膜势能降低。Lenti-circ_UBXN7可以促进细胞迁移，而Lenti-circ_UBXN7-shRNA可以抑制细胞迁移。Lenti-circ_UBXN7可以诱导Twist、N-cadherin、Vimentin蛋白表达增高，并降低E-cadherin蛋白表达；而Lenti-circ_UBXN7-shRNA对各蛋白表达水平的影响则相反。Starbase V2.0软件显示miR-203a与circ_UBXN7存在潜在结合位点，并且在HepG2和HUH-7细胞中miR-203a与circ_UBXN7表达水平呈负相关。 结论： circ_UBXN7在肝癌发生发展中发挥重要促癌作用，有望成为肝癌治疗的潜在靶点。.
To investigate the clinical characteristics of metastatic tumors in small intestine. The clinical manifestations, imaging and endoscopic findings, treatment methods and follow-up of patients with small bowel metastatic tumors admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2022 were retrospectively analyzed. A total of 10 patients were included, including 7 males and 3 females, aged 33-77 (56.4±12.6) years. The main clinical manifestations were intestinal obstruction (8 cases), such as abdominal pain, abdominal distension, nausea, vomiting, and reduced defecation. Some patients had intussusception (abdominal pain, vomiting, black stool and other symptoms, 1 case) or gastrointestinal bleeding (1 case) with early symptoms imperceptible. The primary tumors include gastric cancer (3 cases), malignant melanoma (2 cases), ovarian cancer (2 cases), colon cancer (1 case), rectal cancer (1 case), and lung cancer (1 case). Most of the primary tumors were poorly differentiated (6 cases) or moderately to poorly differentiated (2 cases). The median time from primary tumor surgery to detection of small bowel metastasis [
Objectives Previous studies have confirmed a link between specific inflammatory cytokines and inflammatory bowel disease (IBD), but the causal relationship between them is not completely clear. This Mendelian Randomization (MR) study aims to evaluate the causal relationship between 18 inflammatory cytokines and inflammatory bowel disease. Method Two-sample Mendelian randomization utilized genetic variances associated with IBD from two extensive publicly available genome-wide association studies (GWAS) (Crohn’s Disease (CD): 12,194 cases and 28,072 controls; Ulcerative Colitis (UC): 12,336 cases and 33,609 controls). The data of inflammatory cytokines was acquired from a GWAS including 8,293 healthy participants. We used inverse variance weighted method, MR-Egger, weighted median, simple model and weighted model to evaluate the causal relationship between inflammatory cytokines and IBD. Sensitivity analysis includes heterogeneity and pleiotropy analysis to evaluate the robustness of the results. Results The findings indicated suggestive positive associations between Interleukin-13 (IL-13) and macrophage migration inhibitory factor (MIF) with CD (odds ratio, OR: 1.101, 95%CI: 1.021-1.188, p = 0.013; OR: 1.134, 95%CI: 1.024-1.255, p = 0.015). IL-13 also displayed a significant positive correlation with UC (OR: 1.099, 95%CI: 1.018-1.186, p = 0.016). Stem cell factor (SCF) was suggested to be associated with the development of both CD and UC (OR: 1.032, 95%CI: 0.973-1.058, p = 0.012; OR: 1.038, 95%CI: 1.005-1.072, p = 0.024). Conclusion This study proposes that IL-13 may be a factor correlated with the etiology of IBD (CD and UC), while MIF just be specifically associated with CD. Additionally, SCF appears more likely to be involved in the downstream development of IBD (CD and UC).
Colorectal cancer (CRC) is the third leading cause of cancer-related death in China. It usually originates from the non-cancerous neoplasm polyps of the colon or rectal epithelium. Some polyps will evolve into precancerous lesions and eventually turn into colorectal cancer, Early screening and removal of adenomas can reduce the risk of colorectal cancer if screened. Unfortunately, more than 60% of colorectal cancer cases are attributed to missed polyps. Therefore, a deep learning network referred to as the faster_rcnn_inception_ resnet_v2 model was introduced for the localization and classification of precancerous lesions. It enables high-precision classification of polyps and adenomas under white light endoscopic images. The Mean Average Precision reached 90.645% when the Intersection over Union is set to 0.5. As an aid to clinicians, the model can improve the detection rate of adenomas and the diagnostic accuracy of early CRC.
Abstract The detection of cell viability or the detection of the percentage of live and dead cells in a sample of cells is an important parameter. At present, the common methods for cell viability determination mainly rely on the responses to cell dyes. However, the additional need for cell staining will consequently cause time-consuming and laborious efforts. Furthermore, the determination of cell viability by cell staining is invasive and may damage the internal structure of cells. In this work, we proposed a label-free method to classify live and dead colonic adenocarcinoma cells by 2D light scattering combined with deep learning algorithm. The deep convolutional network of YOLO-v3 was used to identify and classify light scattering images of live and dead HT29 cells. This method achieved an excellent sensitivity (92.16%), specificity (94.23%), and accuracy (93.2%). The results show that the combination of 2D light scattering images and deep neural network may provide a new label-free method for cellular analysis.
The formation of liver fibrosis is mainly caused by the activation of hepatic stellate cells (HSCs) and the imbalance of extracellular matrix (ECM) production and degradation. The treatment of liver fibrosis mainly includes removing the cause, inhibiting the activation of HSCs, and inhibiting inflammation. NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5/NOD27/CLR16.1 (NLRC5) is a highly conserved member of the NLR family and is involved in inflammation and immune responses by regulating various signaling pathways such as nuclear factor-κB (NF-κB) signaling. It has been found that NLRC5 plays an important role in liver fibrosis, but its specific effect and possible mechanism remain to be fully elucidated.To investigate the role of NLRC5 in the activation and reversion of HSCs induced with transforming growth factor-β (TGF-β) and MDI, and to explore its relationship with liver fibrosis.A total of 24 male C57BL/6 mice were randomly divided into three groups, including normal, fibrosis, and recovery groups. Twenty-four hours after a liver fibrosis and spontaneous reversion model was established, the mice were sacrificed and pathological examination of liver tissue was performed to observe the degree of liver fibrosis in each group. LX-2 cells were cultured in vitro and treated with TGF-β1 and MDI. Real-time quantitative PCR (qPCR) and Western blot were used to analyze the expression levels of NLRC5, α-smooth muscle actin (α-SMA), and collagen type I alpha1 (Col1a1) in each group. The activity of NF-κB in each group of cells transfected with NLRC5-siRNA was detected.Compared with the normal mice, the expression level of NLRC5 increased significantly (P < 0.01) in the fibrosis group, but decreased significantly in the recovery group (P < 0.01). In in vitro experiments, the content of NLRC5 was enhanced after TGF-β1 stimulation and decreased to a lower level when treated with MDI (P < 0.01). The expression of α-SMA and Col1a1 proteins and mRNAs in TGF-β1-mediated cells was suppressed by transfection with NLRC5-siRNA (P < 0.01). Western blot analysis showed that the expression of NF-κB p65 protein and phosphorylated IκBα (p-IκBα) was increased in the liver of mice in the fibrosis group but decreased in the recovery group (P < 0.01), and the protein level of nuclear p65 and p-IκBα was significantly increased after treatment with NLRC5-siRNA (P < 0.01).NLRC5 may play a key role in the development and reversal of hepatic fibrosis through the NF-κB signaling pathway, and it is expected to be one of the clinical therapeutic targets.
The long non‑coding RNA (lncRNA) small nucleolar RNA host gene 22 (SNHG22) has been reported as a crucial regulator in several types of human cancer. The present study evaluated the function and mechanism of SNHG22 in colorectal cancer (CRC) progression. SNHG22 expression was detected in colorectal adenoma, CRC tumor tissues (TTs) and adjacent non‑cancerous tissues (ANTs) using reverse transcription‑quantitative PCR (RT‑qPCR). The biological behaviors of SNHG22 in CRC cell lines were explored in vitro using Cell Counting Kit‑8, flow cytometry, wound scratch assay and Transwell assay, and in vivo using a nude mouse xenograft model. The interaction between SNHG22 and microRNA‑128‑3p (miR‑128‑3p), and the target genes of miR‑128‑3p were explored using online tools, RT‑qPCR, western blotting and a dual‑luciferase reporter assay. The present study revealed that SNHG22 expression was most highly expressed in TTs followed by adenoma tissues and ANTs. In addition, high SNHG22 expression levels were significantly associated with advanced clinicopathological factors and worse survival in patients with CRC. SNHG22 knockdown markedly inhibited CRC cell proliferation, apoptosis resistance, migration and invasion in vitro, and hindered tumor growth in vivo. The mechanistic study revealed that SNHG22 bound to miR‑128‑3p and attenuated its inhibitory effects on E2F transcription factor 3 (E2F3) expression levels and activity. Rescue experiments demonstrated that inhibiting miR‑128‑3p or upregulating E2F3 offset the effects of SNHG22 knockdown on CRC cells. The present findings support the existence of an interactive regulatory network involving SNHG22, miR‑128‑3p and E2F3 in CRC cell lines, indicating that the SNHG22/miR‑128‑3p/E2F3 axis may be considered a novel diagnostic and therapeutic target in CRC.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)