Acellular Dermal Matrix Prevents Esophageal Stricture After Full Circumferential Endoscopic Submucosal Dissection in a Porcine Model.

Esophageal stricture is a common complication after endoscopic submucosal dissection (ESD), especially in full circumferential ESD. This study investigated fully covered self-expanding metal stent (FCSEMS) placement with an acellular dermal matrix (ADM) for preventing post-ESD esophageal stricture. Twelve Bama minipigs were randomly divided into two groups, which underwent full circumferential ESD in the distal esophagus. In group A, an FCSEMS with ADM was placed at the mucosal defect, whereas group B underwent standard FCSEMS placement. The stent was removed during gastroscopy 2 weeks after the ESD procedure. At the fourth week, gastroscopy was repeated to evaluate local healing and stenosis. The animals were sacrificed, esophageal specimens were obtained for macroscopic and histological evaluation, and serum C-reactive protein (CRP) levels were quantified. Four weeks post ESD, dysphagia occurrence was lesser in group A than in group B. Group A demonstrated lesser esophageal stricture on macroscopic evaluation (21.02 ± 16.65% vs. 57.41 ± 8.48%, p = 0.001) in the form of enhanced re-epithelization (99.13 ± 0.98% vs. 96.63 ± 1.64%, p = 0.009), diminished submucosal fibrosis (1117.53 ± 188.83 um vs. 1834.69 ± 421.99 um, p = 0.003), and attenuated inflammatory infiltration (121.00 ± 30.66 vs. 188.17 ± 64.92, p = 0.045). The increase in the serum CRP level was lower in group A than in group B at 4 weeks post-ESD. FCSEMS combined with ADM can enhance re-epithelization in the process of wound healing and significantly reduce the degree of esophageal stenosis after circumferential ESD. This study provided important preclinical findings for subsequent clinical trials.

MicroRNA-219a-2-3p modulates the proliferation of thyroid cancer cells via the HPSE/cyclin D1 pathway.

Heparanase (HPSE) is an endo-ß-D-glucuronidase overexpressed in different types of human cancer, and a predicted target of microRNA (miRNA/miR)-219a-2-3p in thyroid cancer. The present study aimed to investigate the potential role of HPSE and miR-219a-2-3p in thyroid cancer, and the molecular mechanism of miR-219a-2-3p regulating the proliferation of thyroid cancer cells via HPSE was confirmed. Immunohistochemistry analysis was performed to detect HPSE expression in thyroid cancer sections. In addition, reverse transcription-quantitative PCR analysis was performed to detect mRNA and miR-219a-2-3p expression levels in thyroid cancer samples and cell lines. miR-219-2-3p mimic or HPSE plasmid were transfected into B-CPAP and TPC-1 thyroid cancer cells. Furthermore, western blot analysis was performed to detect the protein expression levels of HPSE and cyclin D1. Cell cycle analysis was performed using propidium iodide staining and flow cytometry, and EdU incorporation was performed to detect cell proliferation. The results demonstrated that high HPSE expression was significantly associated with tumor size, extracapsular invasion and lymph node metastasis. Notably, a statistically negative correlation was observed between HPSE mRNA expression and miR-219a-2-3p expression in thyroid cancer tumors, as well as in thyroid cancer cell lines. When exogenously expressed in B-CPAP and TPC-1 cells, miR-219a-2-3p induced cell cycle arrest at the G0/G1 phase and decreased the percentage of proliferating cells. Furthermore, HPSE and cyclin D1 protein expression decreased following transfection with miR-219a-2-3p. Notably, when HPSE was ectopically expressed in miR-219a-2-3p transfected cells, cyclin D1 expression and the number of proliferative cells increased. Taken together, these results suggest that HPSE contributes to the proliferation of thyroid cancer cells. In addition, miR-219a-2-3p was confirmed to target HPSE and inhibit cell proliferation, which was associated with cyclin D1 suppression-mediated cell cycle arrest.

Pentraxin 3 is a diagnostic and prognostic marker for ovarian epithelial cancer patients based on comprehensive bioinformatics and experiments.

BACKGROUND: Ovarian epithelial cancer is one of the leading malignant tumors in gynecology and lacks effective diagnostic and prognostic markers. Our study aims to screen and verify ovarian epithelial cancer biomarkers. METHODS: GSE18520 and GSE26712 were downloaded from the GEO database. The "limma" and "WGCNA" packages were used to explore hub genes. The Kaplan-Meier Plotter database was used for survival analysis of the hub genes. Immunohistochemical analysis was used to identify the expression level of Pentraxin 3 in ovarian epithelial cancer samples. RESULTS: In this study, we integrated and analyzed two datasets, GSE18520 and GSE26712, and a total of 238 differentially expressed genes (DEGs) were screened out. Enrichment analysis showed that these DEGs were related to collagen-containing extracellular matrix and other pathways. Further application of WGCNA (weighted gene coexpression network analysis) identified 15 gene modules, with the purple module showing the highest correlation with ovarian epithelial cancer. Twenty-five genes were shared between the purple module and DEGs, 13 genes were related to the prognosis of ovarian epithelial cancer patients, and the PTX3 gene had the highest hazardous risk (HR) value. We performed immunohistochemical analyses on the 255 Pentraxin-3 (PTX3)-based clinical samples. PTX3 was found to be overexpressed in ovarian epithelial cancer and related to the degree of differentiation. The Cox proportional hazard model indicates that high PTX3 expression is an independent risk factor for the prognosis of ovarian epithelial cancer patients. CONCLUSIONS: In conclusion, through WGCNA and a series of comprehensive bioinformatics analyses, PTX3 was first identified as a novel diagnostic and prognostic biomarker for ovarian epithelial cancer.

COVID-19 Epidemic Peer Support and Crisis Intervention Via Social Media.

This article describes a peer support project developed and carried out by a group of experienced mental health professionals, organized to offer peer psychological support from overseas to healthcare professionals on the frontline of the COVID-19 outbreak in Wuhan, China. This pandemic extremely challenged the existing health care systems and caused severe mental distress to frontline healthcare workers. The authors describe the infrastructure of the team and a novel model of peer support and crisis intervention that utilized a popular social media application on smartphone. Such a model for intervention that can be used elsewhere in the face of current global pandemic, or future disaster response.

LncRNA NKILA inhibits the proliferation and promotes the apoptosis of CSCC cells by downregulating miRNA-21.

Long noncoding RNA (lncRNA) NKILA has been well studied in several types of human tumors as a tumor suppressor, while its involvement in cervical squamous cell carcinoma (CSCC) remains unclear. In our studies, we found that serum NKILA was at lower levels and serum microRNA-21 (miRNA-21) was at higher levels in patients with early stage CSCC than in the healthy female. Altered expression of NKILA and miRNA-21 can effectively separate patients with CSCC at an early stage from healthy controls. Serum levels of NKILA were significantly and negatively correlated with miRNA-21 in patients with CSCC but not in normal controls. Overexpression of NKILA mediated the inhibited expression of miRNA-21 in CSCC cells, but mimic transfection of miRNA-21 did not significantly change the expression level of NKILA. Overexpression of NKILA repressed the proliferation and promoted the apoptosis of CSCC cells, while miRNA-21 showed opposite functions. In addition, miRNA-21 mimic transfection reduced the effects of NKILA on CSCC cells. Collectively, lncRNA NKILA could repress the proliferation and promote the apoptosis of CSCC cells by downregulating miRNA-21.

NR2F1-AS1 regulated miR-423-5p/SOX12 to promote proliferation and invasion of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is an aggressive histological subtype of thyroid carcinoma (THCA), whose occurrence rate is high. The participation of long noncoding RNAs in the pathologies of cancers has attracted significant attention during the past decades. The purpose of the current study is to investigate the role of NR2F1 antisense RNA 1 (NR2F1-AS1) in PTC. The expression of NR2F1 in THCA samples was analyzed by bioinformatics tool gene expression profiling interactive analysis. Levels of NR2F1-AS1, microRNA-423-5p (miR-423-5p), and SRY-box 12 (SOX12) were evaluated by a quantitative reverse transcription-polymerase chain reaction and Western blot. The impact of NR2F1-AS1 on PTC cell proliferation and invasion was assessed by Cell Counting Kit-8, EdU, and Transwell invasion assays. The interactions among NR2F1-AS1, miR-423-5p, and SOX12 were determined by RNA immunoprecipitation and luciferase reporter assays. Consequently, we found that NR2F1-AS1 and SOX12 levels were elevated in PTC, whereas miR-423-5p was downregulated in PTC cells. Functionally, NR2F1-AS1 silence led to reduced proliferation and invasion of PTC cells. Mechanistically, NR2F1-AS1 interacted with miR-423-5p to induce SOX12 expression in PTC cells. In conclusion, the present study firstly stated that NR2F1-AS1 regulated miR-423-5p/SOX12 to promote proliferation and invasion of PTC, indicating NR2F1-AS1 as a potential novel target for the molecular-targeted therapy of PTC.

Long non-coding RNA LINC01207 silencing suppresses AGR2 expression to facilitate autophagy and apoptosis of pancreatic cancer cells by sponging miR-143-5p.

Pancreatic cancer is a serious malignancy accompanied by a well-documented poor prognosis. Accumulating studies have indicated the crucial roles played by long non-coding RNAs (lncRNAs) in proliferation, apoptosis and invasion of cancer cells. The aim of the current study was to investigate the role of lncRNA LINC01207 in autophagy and apoptosis of pancreatic cancer cells and its regulatory mechanism interacting with miR-143-5p. Initially, expression profiles of lncRNAs and genes associated with pancreatic cancer were identified. The expression patterns of LINC01207, miR-143-5p and AGR2 in both pancreatic cancer and adjacent tissues were then determined. The binding relationship of LINC01207 to miR-143-5p and targeting relationship of miR-143-5p to AGR2 were subsequently verified. Silencing of LINC01207, or up-regulation or down-regulation of miR-143-5p was introduced into the pancreatic cancer cells, so as to analyze their effects on the cell growth, apoptosis and autophagy. Besides, these regulatory effects were further explored with the determination of the autophagy- and apoptosis-related gene or proteins. LINC01207 and AGR2 were highly expressed while miR-143-5p was poorly expressed in pancreatic cancer. Functionally, LINC01207 can bind to miR-143-5p, and AGR2 was a target gene of miR-143-5p. Importantly, silencing of LINC01207 down-regulated the expression of AGR2 by up-regulating miR-143-5p. Moreover, silencing of LINC01207 and up-regulation of miR-143-5p promoted cell apoptosis and autophagy, corresponding to increased expression of autophagy- and apoptosis-related proteins, in addition to inhibited cell growth. Taken together, silencing of LINC01207 prevents the progression of pancreatic cancer by impairing miR-143-5p-targeted AGR2 expression, providing a potential target for pancreatic cancer treatment.

Fibrosis of mesothelial cell-induced peritoneal implantation of ovarian cancer cells.

BACKGROUND: Peritoneal metastasis frequently occurs in patients with advanced ovarian cancer and is the main basis for a poor prognosis. The mechanism underlying preferential ovarian cancer spread to the peritoneum is not well understood. METHODS: Herein, we investigated the significance and mechanism underlying fibrosis of mesothelial cells promoting peritoneal implantation of ovarian cancer. We have assessed the mesothelial cell fibroblast transformation process in peritoneal tissues of omentum and fibrotic mesothelial cell release of chemokines to promote dissemination by scanning electron microscopy, ELISA, Western blot, and Transwell chamber assay. RESULTS: We showed that the fibrosis of mesothelial cells exists in the peritoneum of ovarian cancer patients with peritoneal metastasis. Fibrosis of the mesothelial cells was induced by TGF-ß1, which upregulates the CXCL12-CXCR4 and CXCL16-CXCR6 axes of mesothelial cells. CONCLUSION: CXCL12-CXCR4 and CXCL16-CXCR6 may be important signaling pathways closely involved in peritoneal metastasis of ovarian cancer that require further investigation. The findings may lead to developing alternative strategies aimed at preventing and treating the metastasis of ovarian cancer.

[Clinicopathologic analysis of spermatocytic seminoma].

OBJECTIVE: To study the clinicopathologic features and biological behavior of spermatocytic seminoma. METHODS: A retrospective analysis of patients diagnosed as seminoma, spermatocytic seminoma between January 2003 and May 2011, was performed. Clinical data, HE stained section and immunohistochemical staining (SP method) were reviewed with follow-up. RESULTS: Sixty-six cases of seminoma and 5 cases of spermatocytic seminoma were identified. The average age at the diagnosis of 5 cases of spermatocytic seminoma was 53 years, and no patient had a history of crytorchidism or germ cell tumor. All five patients had stage pT1 tumor. Immunohistochemical studies showed that spermatocytic seminoma was negative for CK, vimentin, OCT3/4, PLAP, and LCA, and PAS staining was also negative. All five patients were well after operation. In contrast, the average age at diagnosis of the 66 cases of seminoma was 37 years, in which 12% had a history of crytorchidism and 11% were in stage pT2 or the above. Immunohistochemical studies showed that seminoma was positive for OCT3/4, PLAP, and CD117. During the follow-up, 2 patients developed metastasis and 3 patients died of the disease. CONCLUSIONS: Spermatocytic seminoma is rare and appears to follow a benign clinical course Due to its favourable prognosis, further treatment is not necessary after orchidectomy. Accurate pathologic diagnosis is critical for patient management and for avoiding over-treatment.

Shape-controlled synthesis of cuprous oxide nanocrystals via the electrochemical route with H2O-polyol mix-solvent and their behaviors of adsorption.

With H2O-polyols (glycerol, ethylene glycol and polyethylene glycol 400) mix-solvent as media in the NaCl-NaOH-NaNO3 electrolytic system, we developed a simple and efficient electrochemical route for the synthesis of Cu2O nanocrystals with different morphology. The SEM results indicated that electrolytic media and current density had a great influence on the shape of Cu2O crystals. The mono-disperse and uniform sphere Cu2O nanoparticles could be readily obtained in H2O-glycerol (or H2O-ethylene glycol) mix-solvent (1:1 volume ratio) and current density 5 mA/cm2. The sphere Cu2O nanoparticles exhibit excellent adsorption ability for organic dyes (methyl orange, fuchsin acid and methyl blue), which is obviously superior to that of the irregular shape Cu2O crystals prepared in H2O-PEG400 (polyethylene glycol 400) mix-solvent. The present work further confirmed that the adsorption ability of Cu2O crystals was related to their size and shape.

Deficits in dopamine clearance and locomotion in hypoinsulinemic rats unmask novel modulation of dopamine transporters by amphetamine.

Insulin affects brain reward pathways and there is converging evidence that this occurs through insulin regulation of the dopamine (DA) transporter (DAT). In rats made hypoinsulinemic by fasting, synaptosomal DA uptake is reduced. Interestingly, [3H]DA uptake is increased in hypoinsulinemic rats with a history of amphetamine self-administration. The possibility that amphetamine and insulin act in concert to regulate DAT activity prompted this study. Here we show that [3H]DA uptake, measured in vitro and clearance of exogenously applied DA in vivo, is significantly reduced in rats made hypoinsulinemic by a single injection of streptozotocin. Strikingly, amphetamine (1.78 mg/kg, given every other day for 8 days) restored DA clearance in streptozotocin-treated rats but was without effect on DA clearance in saline-treated rats. Basal locomotor activity of streptozotocin-treated rats was lower compared to control rats; however, in streptozotocin-treated rats, hyperlocomotion induced by amphetamine increased over successive amphetamine injections. In saline-treated rats the locomotor stimulant effect of amphetamine remained stable across the four amphetamine injections. These results provide exciting new evidence that actions of amphetamine on DA neurotransmission are insulin-dependent and further suggest that exposure to amphetamine may cause long-lasting changes in DAT function.

The Drosophila acetylcholine receptor subunit D alpha5 is part of an alpha-bungarotoxin binding acetylcholine receptor.

The central nervous system of Drosophila melanogaster contains an alpha-bungarotoxin-binding protein with the properties expected of a nicotinic acetylcholine receptor. This protein was purified 5800-fold from membranes prepared from Drosophila heads. The protein was solubilized with 1% Triton X-100 and 0.5 M sodium chloride and then purified using an alpha-cobratoxin column followed by a lentil lectin affinity column. The purified protein had a specific activity of 3.9 micromol of 125I-alpha-bungarotoxin binding sites/g of protein. The subunit composition of the purified receptor was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. This subunit profile was identical with that revealed by in situ labeling of the membrane-bound protein using the photolyzable methyl-4-azidobenzoimidate derivative of 125I-alpha-bungarotoxin. The purified receptor reveals two different protein bands with molecular masses of 42 and 57 kDa. From sedimentation analysis of the purified protein complex in H2O and D2O and gel filtration, a mass of 270 kDa was calculated. The receptor has a s(20,w) of 9.4 and a Stoke's radius of 7.4 nm. The frictional coefficient was calculated to be 1.7 indicating a highly asymmetric protein complex compatible with a transmembrane protein forming an ion channel. The sequence of a peptide obtained after tryptic digestion of the 42-kDa protein allowed the specific identification of the Drosophila D alpha5 subunit by sequence comparison. A peptide-specific antibody raised against the D alpha5 subunit provides further evidence that this subunit is a component of an alpha-bungarotoxin binding nicotinic acetylcholine receptor from the central nervous system of Drosophila.