Background: Claudins (CLDNs) are a family of closely related transmembrane proteins that have been linked to oncogenic transformation and metastasis across a range of cancers, suggesting that they may be valuable diagnostic and/or prognostic biomarkers that can be used to evaluate patient outcomes. However, CLDN expression patterns associated with colorectal cancer (CRC) remain to be defined. Methods: The mRNA levels of 21 different CLDN family genes were assessed across 20 tumor types using the Oncomine database. Correlations between these genes and patient clinical outcomes, immune cell infiltration, clinicopathological staging, lymph node metastasis, and mutational status were analyzed using the GEPIA, UALCAN, Human Protein Atlas, Tumor Immune Estimation Resource, STRING, Genenetwork, cBioportal, and DAVID databases in an effort to clarify the potential functional roles of different CLDN protein in CRC. Molecular docking analyses were used to probe potential interactions between CLDN4 and TGFβ1. Levels of CLDN4 and CLDN11 mRNA expression in clinical CRC patient samples and in the HT29 and HCT116 cell lines were assessed via qPCR. CLDN4 expression levels in these 2 cell lines were additionally assessed following TGFβ1 inhibitor treatment. Results: These analyses revealed that COAD and READ tissues exhibited the upregulation of CLDN1, CLDN2, CLDN3, CLDN4, CLDN7, and CLDN12 as well as the downregulation of CLDN5 and CLDN11 relative to control tissues. Higher CLDN11 and CLDN14 expression as well as lower CLDN23 mRNA levels were associated with poorer overall survival (OS) outcomes. Moreover, CLDN2 and CLDN3 or CLDN11 mRNA levels were significantly associated with lymph node metastatic progression in COAD or READ lower in COAD and READ tissues. A positive correlation between the expression of CLDN11 and predicted macrophage, dendritic cell, and CD4+ T cell infiltration was identified in CRC, with CLDN12 expression further being positively correlated with CD4+ T cell infiltration whereas a negative correlation was observed between such infiltration and the expression of CLDN3 and CLDN15. A positive correlation between CLDN1, CLDN16, and neutrophil infiltration was additionally detected, whereas neutrophil levels were negatively correlated with the expression of CLDN3 and CLDN15. Molecular docking suggested that CLDN4 was able to directly bind via hydrogen bond with TGFβ1. Relative to paracancerous tissues, clinical CRC tumor tissue samples exhibited CLDN4 and CLDN11 upregulation and downregulation, respectively. LY364947 was able to suppress the expression of CLDN4 in both the HT29 and HCT116 cell lines. Conclusion: Together, these results suggest that the expression of different CLDN family genes is closely associated with CRC tumor clinicopathological staging and immune cell infiltration. Moreover, CLDN4 expression is closely associated with TGFβ1 in CRC, suggesting that it and other CLDN family members may represent viable targets for antitumor therapeutic intervention.
Objective:To evaluate the clinical value of three-dimensional contrast-enhanced MR angiography(3D CE-MRA)in the diseases of aorta.Methods:3D CE-MRA were performed in 50 patients with 1.5T super conductive MR scanner.Postprocessing techniques including original digital subtraction and maximum intensity projection(MIP)and multiplanar reconstrution(MPR)and surface shading display(SSD).Results:In the 50 cases,11 cases are normal,39 cases are abnormal,including thoracic aortic aneurysms in 4 cases,abdominal aortic aneurysms in 4 cases,aortic dissections in 15 cases,aorta atherosclerosis in 13 cases,arteritis in 1 case,aorta aberrance in 2 cases.Thirty-four cases were proved by surgery and/or DSA.Conclusion:3D CE-MRA is a reliable noninvasive method for examining the diseases of the aorta.It has an important role in diagnosing and treating the diseases of aorta.
Current therapeutic strategies for central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) are extremely limited. Secondary central nervous system lymphoma (SCNSL) also shows a grave prognosis and high mortality. This report describes a young female patient with DLBCL and CNS relapse who received low-dose CD19-directed chimeric antigen receptor T (CAR-T) cell therapy followed with Bruton's tyrosine kinase inhibitor and programmed cell death protein 1 antibody after several lines of chemotherapy. However, limited reports on CAR-T cell therapy are applied for SCNSL, particularly those in combination with targeted agents. The current treatment combination for this case provides a new regimen for CNS relapse from DLBCL.ClinicalTrials.gov number, NCT04666168.
BACKGROUND Polysaccharides from bivalves have multiple bioactivities in various aspects of biology. However, the role of a polysaccharide derived from Amusium pleuronectes on potential hepatoprotective effects remains unclear. MATERIAL AND METHODS A water-soluble polysaccharide was isolated from Amusium pleuronectes (APS-1) using ultrasound-assisted hot-water extraction. The molecular weight of APS-1 was approximately 11.7 kDa and was determined by calibration with dextran. APS-1 was analyzed by high-performance liquid chromatography (HPLC), and mainly consisted of a uniform glucose polymer. The protective effect of APS-1 on Schistosoma japonicum-induced liver fibrosis was investigated in a mouse model. RESULTS Treatment with APS-1 increased serum levels of interleukin (IL)-12 and interferon (IFN)-γ, increased superoxide dismutase (SOD) activity, and decreased levels of IL-13 and IL-5, and hyaluronidase activity. Moreover, immunohistochemical analysis revealed that the collagen content of hepatic tissue of APS-1-treated mice, including that of collagen I, II, and IV, was dramatically decreased. Furthermore, our data showed that combined treatment of APS-1 with praziquantel had more pronounced effects than treatment with either APS-1 or praziquantel alone. CONCLUSIONS Our findings suggest that the treatment using APS-1 in combination with praziquantel attenuated S. japonicum egg-induced hepatic fibrosis, and possessed potent hepatoprotective activity.
At present, the use of the common chemotherapy regimen CHOP/R-CHOP for diffuse large B-cell lymphoma (DLBCL) has some shortcomings, especially for relapsed and refractory DLBCL. CD47 is now considered as a prominent target in cancer therapies, and CD47 blockade mainly inhibits the CD47-SIRPα axis to prevent tumor immune escape. Here, we evaluated the effects of the latest CD47 antibodies reported and the correlations of closely related genes with CD47 in this disease. In the future, therapeutic strategies for DLBCL will focus on multitarget antibody combined treatment and multigene joint attacks.
Background: Vitamin C has been used in combination with several target genes in the treatment of leukemia. Tet methylcytosine dioxygenase (Tet2), B-cell lymphoma 2 (Bcl2), and solute carrier family 23 member 2 (Slc23a2) are the major target genes in the treatment of leukemia and are relevant to vitamin C. Materials and Methods: Using whole-genome expression profiles from mouse livers, the expression quantitative trait locus (eQTL), correlation matrix, and gene network graph were constructed with probes from each of these three genes and with their relative genes. The function of key genes was examined by their pathways and reported information. The results indicated that although direct correlations among their expression levels were not strong, alternative connecting pathways were discovered. By comparing the expression levels of one probe with known sequences from each of the three genes, we identified several key genes, induced myeloid leukemia cell differentiation protein (Mcl1), far upstream element-binding protein 1 (Fubp1), and tumor protein D52-like 2 (Tpd52l2), which play important roles in acute lymphocytic leukemia and acute myelocytic leukemia. In conclusion, Alternative pathways and key genes that connect Tet2, Bcl2, and Slc23a2 for their therapeutic applications with vitamin C were identified.
The prognosis of hepatocellular carcinoma (HCC) is very dismal and the targeted drugs of HCC are limited. Studies of HCC prognostic biomarkers have made little progress, though many new techniques such as high-throughput sequencing have been applied. FOS-like antigen 1 (FOSL1) is generally accepted as a proto-oncogene but its clinical significance in HCC has never been elucidated.In our study, we investigated the expression of FOSL1 in 114 paraffin-embedded HCC tissues, and detected FOSL1 mRNA levels in 20 pairs of fresh HCC tissues and their corresponding tumor adjacent tissues. The correlations between FOSL1 expression and clinicopathological factors were analyzed and the prognostic significance of FOSL1 was evaluated with univariate and multivariate analysis. Moreover, we detected the function of FOSL1 in HCC proliferation with experiments in vitro.FOSL1 mRNAs in HCCs were significantly higher than those in tumor adjacent tissues. The percentage of high expression and low expression of FOSL1 accounted for 46% (53/114) and 54% (61/114), respectively. High expression of FOSL1 was significantly associated with larger tumor size (P = 0.021), hepatitis B virus infection (P = 0.014), advanced T stage (P = 0.014), and tumor necrosis metastasis stage (P = 0.014). Moreover, high expression of FOSL1 was significantly correlated with poor prognosis of HCC and could be identified as an independent prognostic biomarker of HCC (hazard ratio = 5.60, 95% confidence interval = 3.00-10.45, P < 0.001). With in vitro function assay, we demonstrated that FOSL1 played an essential role in HCC proliferation.High expression of FOSL1 is an independent risk factor of HCC predicting unfavorable prognosis, indicating that FOSL1 detection could stratify patients with high risk, and anti-FOSL1 therapy may be a promising way to treat HCC.
BACKGROUND:The objective of this study was to investigate the molecular mechanism by which miR-637 interferes with the expression of CDK6, which contributes to the development of pulmonary hypertension (PH) with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS:We used an online miRNA database to identify CDK6 as a virtual target of miR-637, and validated the hypothesis using luciferase assay. Furthermore, we transfected SMCs with miR-637 mimics and inhibitor, and expression of CDK6 was determined using Western blot and real-time PCR. RESULTS:In this study, we identified CDK6 as a target of miR-637 in smooth muscle cells (SMCs), and determined the expression of miR-637 in SMCs from PH patients with COPD and normal controls. We also identified the exact miR-637 binding site in the 3’UTR of CDK6 by using a luciferase reporter system. The mRNA and protein expression levels of CDK6 in SMCs from PH patients with COPD were clearly upregulated compared with the normal controls. Cells exposed to hypoxia also showed notably increased CKD6 mRNA and protein expression levels, and when treated with miR-637 or CDK6 siRNA, this increase in CKD6 expression was clearly attenuated. Additionally, cell viability and cell cycle analysis showed that hypoxia markedly increased viability of SMCs by causing an accumulation in S phase, which was relieved by the introduction of miR-637 or CDK6 siRNA. CONCLUSIONS:Our study proved that the CDK6 gene is a target of miR-637, and demonstrated the regulatory association between miR-637 and CDK6, suggesting a possible therapeutic target for PH, especially in patients with COPD.
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