The management of early gastric cancer (EGC) has witnessed a rise in the utilization of endoscopic submucosal dissection (ESD) as a treatment modality, although prognostic markers are needed to guide management strategies. This study investigates the prognostic implications of lymphovascular invasion (LVI) in ESD-eligible EGC patients, specifically its implications for subsequent radical surgery.
Objective: Previous basic studies on the use of titanized polypropylene meshes in abdominal external hernia repair are not only limited, but also highly controversial. This study aims to investigate the modification effect of titanium compounds on polypropylene materials and compare the performance of two kinds of meshes both in vivo and in vitro . Methods: Human peritoneal mesothelial cells (HMrSV5), human epidermal fibroblasts (HSF), and human monocytic cells (THP-1) were cultured in vitro to simulate the abdominal external hernia environment. Titanized polypropylene meshes (Ti) and polypropylene mesh (Non-Ti) were co-cultured with the cells respectively. The effects of titanium compounds on cell growth were determined by cell activity and apoptosis, and the growth of cells on the mesh surface was assessed using a scanning electron microscope and a confocal microscope. In vivo experiments, different sizes titanized polypropylene meshes and polypropylene meshes were placed between the external oblique abdominal muscle and the internal oblique abdominal muscle, the parietal peritoneum, the serous layer of the descending colon, and the underside of the femoral nerve in rabbits. The effects of titanium compounds were evaluated by observing the anti-adhesion, anti-contraction, anti-fibrotic properties, and effects on nerves of the mesh. Results: Titanium compounds effectively reduced the effects of polypropylene material on cell growth, and improved the fixation and adhesion of HMrSV5, HSF and THP-1 (M0) on the surface of titanized polypropylene meshes. Furthermore, titanium compounds improved the adhesion, contraction and fibrosis of polypropylene material, as well as reduced nerve damage. This improvement demonstrated a regular trend with the type of titanized polypropylene meshes. Conclusion: The titanium compounds improved the biocompatibility of the polypropylene material, which was conducive to the fixation and adhesion of cells on the surface of the meshes, and alleviated the adhesion and contraction of the meshes, and the degree of tissue fibrosis, as well as the influence on nerves.
Abstract The subtypes of serous ovarian tumors (SOTs), including benign serous cystadenoma, serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSC), and high-grade serous ovarian carcinoma (HGSC), remain poorly understood. Herein, we aimed to characterize the cell adhesion molecule 1 (CADM1)/signal transducer and activator of transcription 3 (STAT3)/human epidermal growth factor receptor 2 (HER2) axis and identify its clinical significance in patients with serous cystadenoma, SBT, LGSC, and HGSC. The immunohistochemical expression of CADM1, HER2, and STAT3 was assessed in 180 SOT specimens, and its association with clinical data was determined. High levels of CADM1 expression were detected in 100% of serous cystadenomas and 83.33% of SBTs, while a loss of CADM1 expression was observed in 44% of LGSCs and 72.5% of HGSCs. Relative to the levels in benign cystadenomas and SBTs, higher levels of HER2 and STAT3 expression were observed in LGSCs and aggressive HGSCs. Furthermore, the expression profile of the CADM1/HER2/STAT3 axis was significantly associated with histologic type, International Federation of Gynecology and Obstetrics stage, and lymph node metastasis in patients with SOT. Our study identified the changes in the CADM1/HER2/STAT3 axis that were closely associated with the clinical behavior of SOTs. These molecular data may provide new insights into SOT carcinogenesis and aid in the diagnosis and treatment of patients with SOT.
Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a novel type of regulated cell death that is associated with various cancers and diseases. However, its relation to AS is not clear. In the present study, we identified two potential therapeutic targets for AS based on genes associated with ferroptosis and explored their association with immune cells and immune cell infiltration (ICI). We studied gene expression profiles of two cohorts of patients with AS (GSE25101 and GSE41038) derived from the gene expression omnibus database, and ferroptosis-associated genes (FRGs) were obtained from the FerrDb database. LASSO regression analysis was performed to build predictive models for AS based on FRGs, and the ferroptosis level in each sample was assessed via single-sample gene set enrichment analysis. Weighted gene co-expression network and protein-protein interaction network analyses were performed for screening; two key genes, DDIT3 and HSPB1, were identified in patients with AS. The relationship between key genes and ICI levels was assessed using the CIBERSORT algorithm, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, DDIT3 and HSPB1 were identified as diagnostic markers and potential therapeutic targets for AS. DDIT3 was highly positively correlated with the infiltration levels of various immune cells, while HSPB1 was negatively correlated with the infiltration levels of several different types of immune cells. In conclusion, DDIT3 and HSPB1 may induce ferroptosis in the cells of patients with AS via changes in the inflammatory response in the immune microenvironment, and these genes could serve as molecular targets for AS therapy.
Dysregulation of microRNAs (miRNAs) is involved in abnormal development and pathophysiology in the brain.Although miR-20b plays essential roles in various human diseases, its function in cerebral ischemic stroke remains unclear.A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) and A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were constructed.qRT-PCR and western blot were used to evaluate the expression of miR-20b and TXNIP.Cell viability was detected by MTT assay, and cell apoptosis was evaluated by flow cytometry.Targetscan and Starbase were used to predict the potential targets of miR-20b.Luciferase reporter assay was applied to determine the interaction between miR-20b and TXNIP.Rescue experiments were conducted to confirm the functions of miR-20b/TXNIP axis in cerebral ischemic stroke.MiR-20b was significantly downregulated after I/R both in vitro and in vivo.Upregulation of miR-20b inhibited OGD/R-induced neurons apoptosis and attenuated ischemic brain injury in rat model.Bioinformatic prediction suggested that TXNIP might be a target of miR-20b, and luciferase reporter assay revealed that miR-20b negatively regulated TXNIP expression by directly binding to the 3'-UTR of TXNIP.Downregulation of TXNIP inhibited OGD/R-induced neurons apoptosis in vitro and ischemic brain injury in vivo.Rescue experiments indicated that downregulation of TXNIP effectively reversed the effect of miR-20b inhibitor in neurons apoptosis after OGD/R-treatment and ischemic brain injury in a mouse model after MCAO/R-treatment.Our study demonstrated that upregulation of miR-20b protected the brain from ischemic brain injury by targeting TXNIP, extending our understanding of miRNAs in cerebral ischemic stroke.
Cadmium (Cd) is a noxious heavy metal widely dispersed in aquatic systems. Parental Cd exposure of fish species at environmental concentrations has been shown to cause deformities and stunted growth in their offspring. However, the long-term effects and the mechanisms underlying parental Cd exposure in fish species on Cd sensitivity in their offspring remain unclear. To explore the impacts of parental Cd exposures on Cd sensitivity, rare minnow (Gobiocypris rarus) larvae whose parents were exposed to Cd at 0, 5 or 10 μg/L for 28 days were established. Results showed that parental Cd exposure in rare minnow increased the Cd content of its larvae. In terms of malformation rate, mortality rate and total length at 7 days of rare minnow larvae, parental Cd exposure at 5 or 10 μg/L reduced Cd sensitivity. Further mechanistic investigation demonstrated that parental Cd exposure significantly upregulated the expression of antioxidant gene regulated by nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-кB) in rare minnow larvae. In addition, parental Cd exposure significantly elevated the level of reactive oxygen species (ROS) and malondialdehyde (MDA), but markedly decreased catalase (CAT), superoxide dismutase (SOD) and oxidized glutathione (GST) activity. The impact of parental Cd exposure to metallothionein (MT) content and the expression of MT mRNA, a detoxifying metallothionein, showed that parental Cd exposure of rare minnow induced oxidative stress in the larvae. Meanwhile, these results indicated that parental Cd exposure in rare minnow reduced the Cd sensitivity of the larvae via activating the Nrf2-mediated antioxidant system. This project helps us to further understand the toxicological mechanism of Cd in fish species and properly assess its potential ecological risk.
This study built an electrochemical label-free progesterone aptasensor to detect progesterone (P4) levels in environmental water samples. The truncated aptamer-modified sulfhydryl adopted self-assembly as a way to stably immobilize at the electrode surface modified by gold nanoparticles (AuNPs). When progesterone combines with the aptamer, the complexes will inhibit electrode surface electron transfer, which reduces the redox peak current value of [Fe(CN) 6 ] 3−/4− . As a result, the amount of progesterone combined with the aptamer on the electrode reacted to the electric current’s response values. We have established the relationship between the concentration of progesterone and the current change by a standard curve that is ΔI ( μ A) = 11.78log C P4 (nM)+48.98. The coefficient of association was 0.9358. The test ranges were from 0.5 nM to 1000 nM. At the same time, other molecules with a similar structure, such as testosterone, estradiol, and 17 α -hydroxyl progesterone, had lower response interference than P4. In conclusion, the aptasensor, which had outstanding repeatability and stability, could be applied to determine P4. Food hygiene and clinical diagnosis can be made easier with this newly developed electrochemical biosensor based on aptamers.
Matrix metalloproteinase 14 (MMP-14), a membrane-anchored MMP that promotes the tumorigenesis and aggressiveness, is highly expressed in gastric cancer. However, the transcriptional regulators of MMP-14 expression in gastric cancer still remain largely unknown. In this study, through mining computational algorithm programs and chromatin immunoprecipitation datasets, we identified adjacent binding sites of myeloid zinc finger 1 (MZF1) and miRNA-337-3p (miR-337-3p) within the MMP-14 promoter. We demonstrated that MZF1 directly bound to the MMP-14 promoter to facilitate its nascent transcription and expression in gastric cancer cell lines. In contrast, endogenous miR-337-3p suppressed the MMP-14 expression through recognizing its binding site within MMP-14 promoter. Mechanistically, miR-337-3p repressed the binding of MZF1 to MMP-14 promoter via recruiting Argonaute 2 and inducing repressive chromatin remodeling. Gain- and loss-of-function studies demonstrated that miR-337-3p suppressed the growth, invasion, metastasis, and angiogenesis of gastric cancer cells in vitro and in vivo through repressing MZF1-facilitated MMP-14 expression. In clinical specimens and cell lines of gastric cancer, MZF1 was highly expressed and positively correlated with MMP-14 expression. Meanwhile, miR-337-3p was under-expressed and inversely correlated with MMP-14 levels. miR-337-3p was an independent prognostic factor for favorable outcome of gastric cancer, and patients with high MZF1 or MMP-14 expression had lower survival probability. Taken together, these data indicate that miR-337-3p directly binds to the MMP-14 promoter to repress MZF1-facilitatd MMP-14 expression, thus suppressing the progression of gastric cancer.
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