A novel aging-associated lncRNA signature for predicting prognosis in osteosarcoma.

Osteosarcoma (OS) is one of the most prevalent bone tumors in adolescents, and the correlation between aging and OS remains unclear. Currently, few accurate and reliable biomarkers have been determined for OS prognosis. To address this issue, we carried out a detailed bioinformatics analysis based on OS with data from the Cancer Genome Atlas data portal and Human Aging Genomic Resources database, as well as in vitro experiments. A total of 88 OS samples with gene expression profiles and corresponding clinical characteristics were obtained. Through univariate Cox regression analysis and survival analysis, 10 aging-associated survival lncRNAs (AASRs) were identified to be associated with the overall survival of OS patients. Based on the expression levels of the 10 AASRs, the OS patients were classified into two clusters (Cluster A and Cluster B). Cluster A had a worse prognosis, while Cluster B had a better prognosis. Then, 5 AASRs were ultimately included in the signature through least absolute shrinkage and selection operator-Cox regression analysis. Kaplan‒Meier survival analysis verified that the high-risk group exhibited a worse prognosis than the low-risk group. Furthermore, univariate and multivariate Cox regression analyses confirmed that the riskScore was an independent prognostic factor for OS patients. Subsequently, we discovered that the risk signature was correlated with the properties of the tumor microenvironment and immune cell infiltration. Specifically, there was a positive association between the risk model and naïve B cells, resting dendritic cells and gamma delta T cells, while it was negatively related to CD8+ T cells. Finally, in vitro experiments, we found that UNC5B-AS1 inhibited OS cells from undergoing cellular senescence and apoptosis, thereby promoting OS cells proliferation. In conclusion, we constructed and verified a 5 AASR-based signature, that exhibited excellent performance in evaluating the overall survival of OS patients. In addition, we found that UNC5B-AS1 might inhibit the senescence process, thus leading to the development and progression of OS. Our findings may provide novel insights into the treatment of OS patients.

Effectiveness of the Interventional Technique for the Removal of Self-Expanding Metallic Esophageal Stents Under Fluoroscopy.

RATIONALE AND OBJECTIVES: Timely removal of esophageal stents can help avoid or reduce the occurrence of complications. This study was aimed at elucidating the interventional technique for the removal of self-expanding metallic esophageal stents (SEMESs) under fluoroscopy and analyzing its safety and efficacy. MATERIALS AND METHODS: The medical records of patients who underwent removal of SEMESs by interventional techniques under fluoroscopy were retrospectively analyzed. Furthermore, the success and adverse event rates for different interventional techniques of stent removal were analyzed and compared. RESULTS: Overall, 411 patients were included, and 507 metallic esophageal stents were removed. There were 455 and 52 fully and partially covered SEMESs, respectively. According to the stent indwelling time, benign esophageal diseases were divided into two groups: ≤68 days and >68 days. There was a significant difference in the incidence of complications between the two groups (13.1% and 30.5%, respectively, p < .001). The stents in cases of malignant esophageal lesions were divided into the following two groups: ≤52 days and >52 days. Intergroup differences in complication incidence were not significant (p = .81) Further, there was a significant difference in removal time between the recovery line pull and proximal adduction techniques (4 and 6 minutes, respectively, p < .001). In addition, the recovery line pull technique was associated with a lower rate of complications (9.8% vs 19.1 %, p = .04). There was no statistical difference in the technical success rate and incidence of adverse events between the inversion and stent-in-stent techniques. CONCLUSION: Interventional technique to remove SEMESs under fluoroscopy is safe, effective, and worthy of clinical application.

Identification and validation of immunotherapy for four novel clusters of colorectal cancer based on the tumor microenvironment.

The incidence and mortality of colorectal cancer (CRC) are increasing year by year. The accurate classification of CRC can realize the purpose of personalized and precise treatment for patients. The tumor microenvironment (TME) plays an important role in the malignant progression and immunotherapy of CRC. An in-depth understanding of the clusters based on the TME is of great significance for the discovery of new therapeutic targets for CRC. We extracted data on CRC, including gene expression profile, DNA methylation array, somatic mutations, clinicopathological information, and copy number variation (CNV), from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) (four datasets-GSE14333, GSE17538, GSE38832, and GSE39582), cBioPortal, and FireBrowse. The MCPcounter was utilized to quantify the abundance of 10 TME cells for CRC samples. Cluster repetitive analysis was based on the Hcluster function of the Pheatmap package in R. The ESTIMATE package was applied to compute immune and stromal scores for CRC patients. PCA analysis was used to remove batch effects among different datasets and transform genome-wide DNA methylation profiling into methylation of tumor-infiltrating lymphocyte (MeTIL). We evaluated the mutation differences of the clusters using MOVICS, DeconstructSigs, and GISTIC packages. As for therapy, TIDE and SubMap analyses were carried out to forecast the immunotherapy response of the clusters, and chemotherapeutic sensibility was estimated based on the pRRophetic package. All results were verified in the TCGA and GEO data. Four immune clusters (ImmClust-CS1, ImmClust-CS2, ImmClust-CS3, and ImmClust-CS4) were identified for CRC. The four ImmClusts exhibited distinct TME compositions, cancer-associated fibroblasts (CAFs), functional orientation, and immune checkpoints. The highest immune, stromal, and MeTIL scores were observed in CS2, in contrast to the lowest scores in CS4. CS1 may respond to immunotherapy, while CS2 may respond to immunotherapy after anti-CAFs. Among the four ImmClusts, the top 15 markers with the highest mutation frequency were acquired, and CS1 had significantly lower CNA on the focal level than other subtypes. In addition, CS1 and CS2 patients had more stable chromosomes than CS3 and CS4. The most sensitive chemotherapeutic agents in these four ImmClusts were also found. IHC results revealed that CD29 stained significantly darker in the cancer samples, indicating that their CD29 was highly expressed in colon cancer. This work revealed the novel clusters based on TME for CRC, which would guide in predicting the prognosis, biological features, and appropriate treatment for patients with CRC.

FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells.

Background: Immune checkpoint inhibitors (ICIs) have rapidly revolutionized colorectal cancer (CRC) treatment, but resistance caused by the heterogeneous tumor microenvironment (TME) still presents a challenge. Therefore, it is necessary to characterize TME immune infiltration and explore new targets to improve immunotherapy. Methods: The compositions of 64 types of infiltrating immune cells and their relationships with CRC patient clinical characteristics were assessed. Differentially expressed genes (DEGs) between "hot" and "cold" tumors were used for functional analysis. A prediction model was constructed to explore the survival of CRC patients treated with and without immunotherapy. Finally, fatty acid-binding protein (FABP6) was selected for in vitro experiments, which revealed its roles in the proliferation, apoptosis, migration, and immunogenicity of CRC tissues and cell lines. Results: The infiltration levels of several immune cells were associated with CRC tumor stage and prognosis. Different cell types showed the synergistic or antagonism infiltration patterns. Enrichment analysis of DEGs revealed that immune-related signaling was significantly activated in hot tumors, while metabolic process pathways were altered in cold tumors. In addition, the constructed model effectively predicted the survival of CRC patients treated with and without immunotherapy. FABP6 knockdown did not significantly alter tumor cell proliferation, apoptosis, and migration. FABP6 was negatively correlated with immune infiltration, and knockdown of FABP6 increased major histocompatibility complex (MHC) class 1 expression and promoted immune-related chemokine secretion, indicating the immunogenicity enhancement of tumor cells. Finally, knockdown of FABP6 could promote the recruitment of CD8+ T cells. Conclusion: Collectively, we described the landscape of immune infiltration in CRC and identified FABP6 as a potential immunotherapeutic target for treatment.

Stent-in-stent technique under fluoroscopy for removal of embedded esophageal stent: a retrospective case series.

Background: Treatment of complications after esophageal stent placement and methods for removal of stents need to be improved. The purpose of this study was to evaluate the safety and efficacy of stent-in-stent (SIS) removal of esophageal stent under fluoroscopy. Methods: This study analyzed the clinical data of consecutive patients undergoing esophageal stent removal by the SIS technique under fluoroscopy. The procedure was performed under local anesthesia on conscious sedated patients. Under fluoroscopy, a second esophageal stent was released within the lumen of the first esophageal stent. The second stent was larger than the first, with both ends protruding 1-2 cm beyond the ends of the first stent. Four weeks later, both esophageal stents were removed by the SIS technique under fluoroscopy. All procedures were performed by the same interventional radiologist (with >10 years of experience). Results: A total of 25 patients were treated by the SIS removal technique. In 23 patients, the first esophageal stent was easily removed by the SIS technique; in the other 2 patients, stent fracture occurred, and some residual nitinol wire had to be removed endoscopically. No serious complications occurred in any patient. Conclusions: The SIS removal technique appears to be a safe and effective method for removal of embedded esophageal metallic stents.

Inversion technique under fluoroscopy for removal of self-expanding nitinol esophageal stent after long-term placement: review of 107 consecutive cases.

BACKGROUND: Removal of self-expanding esophageal metal stents that have been implanted for a long time can be difficult and risky. PURPOSE: In this paper, we describe the use of the "inversion technique" under fluoroscopy for removal of self-expandable nitinol esophageal stents that have been placed for long periods and evaluate the effectiveness and safety of the method. METHODS: Retrospective analysis of patients who underwent removal of self-expanding nitinol esophageal stents by the inversion technique under fluoroscopy at our center. Demographic characteristics, type of esophageal stents, stent retention time, reasons for stent removal, and related complications were collected from the case records and analyzed. RESULTS: A total of 112 metal esophageal stents (62 fully covered esophageal stents and 50 partially covered esophageal stents) were extracted from the 107 patients included in the study. Indications for stent implantation were malignant esophageal stenosis (27 patients), benign esophageal stenosis (42 patients), and esophageal fistula (38 patients). Median duration of stent retention was 77 days (29-727 days). All stents were removed successfully without major complications such as esophageal rupture, massive hemorrhage, asphyxia, or cardiorespiratory arrest. CONCLUSION: Inversion technique under fluoroscopy appears to be a safe, effective, and quick procedure for removal of self-expanding nitinol esophageal stent after long-term placement.

Comprehensive Analyses of Stromal-Immune Score-Related Competing Endogenous RNA Networks In Colon Adenocarcinoma.

Although recent clinical investigations emphasize the roles of myriad diversities of RNAs in stromal and immune components in the tumor microenvironment, especially in colon adenocarcinoma, however, analyses of "competing endogenous RNAs (ceRNA)" network in association with stromal and immune scores have yet to be determined. This study was conducted to explore the regulatory mechanisms of a stromal-immune score-based ceRNA network in colon adenocarcinoma. Stromal and immune scores of colon adenocarcinoma tumor samples were calculated by using the ESTIMATE algorithm. Differential expression analysis between samples with high/low stromal and immune scores was performed, followed by functional annotation for the overlapping DEmRNAs. The ceRNA network was constructed by differential expression analysis, prediction of RNA-RNA interaction, and correlation with clinicopathological parameters of the patients, which were further verified by external datasets and experiments. Colon adenocarcinoma patients having higher immune scores exhibited prolonged overall survival. RNA dataset analyses from TCGA revealed aberrant expressions of a total of 2052 mRNAs, 108 lncRNAs, and 70 miRNAs between high and low stromal/immune groups. Functional annotation mapped the differentially overexpressed mRNAs for immune-associated GO terms. To construct the ceRNA network, a total of 48 lncRNAs, 40 miRNAs, and 199 mRNAs were sorted out. A dysregulated ceRNA network consisting of 6 lncRNAs, 11 miRNAs, and 39 mRNAs was constructed by comparing RNA expressions between cancer as well as adjacent normal tissues. The ceRNA regulatory axis "MIAT/miR-532-3p/STC1" was regarded as a potential hit by the comprehensive analysis. The RT-qPCR assay showed upregulation of MIAT and STC1 while downregulation of hsa-miR-532-3p expression in cancer. Thus, our study highlights the potential role of a stromal-immune score-based ceRNA network in the colon adenocarcinoma microenvironment. The ceRNA axis MIAT/miR-532-3p/STC1 could serve as a promising therapeutic target for colon adenocarcinoma.

Balloon dilatation complications during esophagogastric anastomotic stricture treatment under fluoroscopy: Risk factors, prevention, and management.

BACKGROUND: Balloon dilatation (BD) is a common treatment for esophagogastric anastomotic stricture (EAS), but with complications. This study investigates the risk factors, prevention, and management of BD complications to provide clinical guidance. METHODS: We retrospectively analyzed the clinical data of 378 patients with EAS treated by BD from March 2011 to June 2021. The association between esophagogastric anastomotic rupture outcome and patient and stricture characteristics and treatment were analyzed by logistic regression. RESULTS: BD was performed 552 times and technical success, 98.0%; overall clinical success, 97.8%; major adverse events, 1.3%; minor adverse events, 9.4%; mortality, 0.3%. Logistic regression showed that age (p = 0.080), sex (p = 0.256), interval from surgery to stricture development (p = 0.817), number of dilatations (p = 0.054), cause of stricture (p ≥ 0.168), and preoperative chemotherapy (p = 0.679) were not associated with anastomotic rupture. Balloon diameter (p < 0.001), preoperative radiotherapy (p = 0.003), and chemoradiotherapy (p = 0.021) were correlated with anastomotic rupture. All patients with type I and II ruptures resumed oral feeding without developing into type III rupture. Type III rupture occurred in six cases, who resumed oral feeding after 7-21 days of nasal feeding and liquid feeding. One patient died of massive bleeding after BD. CONCLUSIONS: Symptomatic treatment for type I and II ruptures and transnasal decompression and jejunal nutrition tubes for type III rupture, are suggested pending rupture healing. Tumor recurrence, preoperative radiotherapy, and balloon diameter affected the anastomotic rupture outcome.

In vitro and vivo study of tranilast protects from acute respiratory distress syndrome and early pulmonary fibrosis induced by smoke inhalation.

BACKGROUND: Tranilast (N-[3＇,4＇-dimethoxycinnamoyl]-anthranilic acid) is an analog of a tryptophan metabolite. It was identified with anti-inflammatory and antifibrotic activities, and used in the treatment of a variety of diseases, such as anti - allergy, bronchial asthma, and hypertrophic scars. As a drug with few adverse reactions, tranilast has attracted great attention, but its application is limited due to the uncertainty of dosages and mechanisms. In this study, the protection effects of different doses of tranilast on smoke inhalation mediated lung injury on rats, and on the damage of three kinds of lung cells in vitro were investigated. METHOD: In vivo, Sprague-Dawley rats were randomly divided into sham group, smoke group (rats were exposed to pine sawdust smoke three times, each time for 5 min), different doses of tranilast treatment group (doses were 100 mg/kg, 200 mg/kg and 300 mg/kg, ip.) and placebo group. After 1, 3 and 7 days, pulmonary function, pathologic injury by HE staining, cytokines and oxidative stress level by kits were determined. At 7days, lung fibrosis was assessed by Masson's trichrome staining and the level of hydroxyproline (HYP). In vitro, three kinds of lung cells from normal rats were isolated: type II alveolar epithelial cells (AT-II), pulmonary microvascular endothelial cells (PMVECs) and pulmonary fibroblasts (PFs). To investigate the potential effects of tranilast on cell proliferation, cell cycle and cytokine production of three kinds of lung cells exposed to smoke. RESULTS: Compared with smoke group and placebo group, tranilast treatment significantly reduced histopathological changes (such as pulmonary hemorrhage, edema and inflammatory cell infiltration, etc.), significantly reduced histopathological score (p < 0.05), increased arterial oxygen partial pressure, and decreased the levels of IL-1ß, TNF-α, TGF-ß1 (p < 0.05), oxidative stress and the expression of nuclear transcription factor κB (NF-κB) smoke exposed rats (p < 0.01). In particular, the effect of 200 mg/kg dose was more prominent. In vitro, smoke induced AT-II and PMVECs apoptosis, improved PFs proliferation (p < 0.01), activity of SOD and decreased the content of MDA (p < 0.01). However, tranilast seems to be turning this trend well. The inflammatory factor IL-11ß, TNF-α and TGF-ß1, and the expression of NF-κB were significantly lower in the tranilast treatment than in the smoke group (p < 0.01). CONCLUSION: This study indicates that tranilast had a protective effect on acute respiratory distress syndrome and early pulmonary fibrosis of rats in vivo. In addition, tranilast promotes proliferation of AT-II and PMVECs but inhibits PFs proliferation, down-regulates secretion of inflammatory cytokines and alleviates oxidative stress of AT-II, PMVECs and PFs after smoke stimuli in vitro.

ATAD2 drives colorectal cancer progression by regulating TRIM25 expression via a positive feedback loop with E2F transcriptional factors.

ATPase family AAA domain-containing protein 2 (ATAD2) is highly expressed in a variety of cancer types, and acts as a co-activator of androgen and estrogen receptors, as well as MYC and E2F transcription factors, to promote tumor cell proliferation. However, the regulation of ATAD2 and its related mechanisms are still elusive. Here, we show that ATAD2 protein was stabilized during DNA damage response in colorectal cancer (CRC) cells. TRIM25, an oncogenic ubiquitin E3 ligase, can interact with ATAD2 and stabilize ATAD2 upon genotoxic insult. We further demonstrated that ATAD2 played a tumor promoting role in CRC and acted as a transcriptional co-activator of E2Fs to promote the expression of TRIM25. Thus, our results revealed an unknown ATAD2-E2Fs-TRIM25 positive feedback loop that drove CRC progression.

Safety and efficacy of large balloon dilatation under fluoroscopy.

The maximum diameter of the balloon used for balloon dilatation(BD) of esophagogastric anastomotic stricture (EAS) is generally 20 millimeters. This study aimed to evaluate the safety and efficacy of BD under fluoroscopy, using balloons with a diameter of 25-30 millimeters. We retrospectively analyzed the data of patients with benign EAS treated by large BD (balloon diameter, 25-30 mm) under fluoroscopy. The Cox proportional hazards model (PHM) was used to identify the factors associated with stricture-free survival. The results show that a total of 127 patients were included in this study, and 204 BDs were performed. The technical success rate was 96.6%, and the clinical success rate was 99.2%. The incidence of serious adverse events was 3.4% (7/204). One patient died of massive hemorrhage during BD, and nine patients were lost to follow-up. For the remaining 117 patients, the median stricture-free survival period was 14.9 months. In multivariable analysis using the Cox PHM, only balloon diameter was significantly associated with stricture-free survival. The stricture-free survival period tended to increase as balloon diameter increased. Large BD under fluoroscopy appears to be safe and effective for the treatment of benign EAS after esophagectomy.

LncRNA KCNQ1OT1 as a miR-26a-5p sponge regulates ATG12-mediated cardiomyocyte autophagy and aggravates myocardial infarction.

BACKGROUND: As a dominant cardiovascular disease, myocardial infarction (MI) causes a considerable mortality globally. KCNQ1 overlapping transcript 1 (KCNQ1OT1) was reported to be overexpressed in MI patients. However, the detailed mechanisms remain unclear. METHODS: We analyzed the expression of KCNQ1OT1 in the serum of MI patients, and built ischemia/reperfusion (I/R) mouse and H/R-induced cell model. TTC staining was used to evaluate infarct size in mice. TUNEL was employed to assess cell apoptosis. QRT-PCR was performed to detect the expression of KCNQ1OT1 and miR-26a-5p. The formation of autophagosomes in cells was detected by immunofluorescence. Caspase3 activity was detected by the Caspase-3 Assay Kit. Autophagy and apoptosis-related proteins were assessed by western blotting. Luciferase reporter assay was used to assess the binding relationship of KCNQ1OT1 and miR-26a-5p and miR-20a-5p/ATG12. RESULTS: KCNQ1OT1 was up-regulated while miR-26a-5p was decreased in MI patients, I/R mouse and H/R-induced cell model. KCNQ1OT1 knockdown inhibited cell autophagy and protected cardiomyocytes from apoptosis by up-regulating miR-26a-5p. Either KCNQ1OT1 knockdown or miR-26a-5p mimics caused inhibition of autophagy related 12 homolog (ATG12), which was the direct target of miR-26a-5p. In vivo, KCNQ1OT1 promoted cardiomyocytes apoptosis via miR-26a-5p/ATG12 pathway. CONCLUSION: KCNQ1OT1/miR-26a-5p/ATG12 axis regulated cardiomyocyte autophagy and apoptosis, both in vivo and in vitro. These data supported that KCNQ1OT1 inhibition might be a promising therapeutic option for protection after MI.

Immunomodulatory property and its regulatory mechanism of double network hydrogel on dendritic cells.

Modulation of the key immune cell subsets by biomaterial has emerged as a potential target to promote tissue repair and regeneration. Based on calcium alginate (Alg) and glycol chitosan (GC), an injectable double-network (DN) hydrogel has been developed as a scaffold for cell delivery and cell cocultured system. Previous studies have documented the interaction between dendritic cells (DCs) and GC or Alg hydrogel, but the potential effect of DN hydrogel on activation of DCs still remains unclear. This research was conducted to explore the immunomodulatory influence and underlying mechanisms of GC/Alg DN hydrogel on DCs in vitro and in vivo. Stimulation of DCs with DN hydrogel obviously induced the maturation of DCs in vitro. In vivo, DN hydrogel did not have obvious influence on the maturation of splenic DCs on postimplantation days 3, 10, and 30. Mechanistically, we found that DN hydrogel induced the maturation of DCs via phosphorylation of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin in vitro. It provides a novel understanding of the immunomodulatory property of DN hydrogel on DCs, which may serve as potential target for designing immune-mediated regenerative strategies.

TMT proteomics analysis of intestinal tissue from patients of irritable bowel syndrome with diarrhea: Implications for multiple nutrient ingestion abnormality.

Diarrheal irritable bowel syndrome (IBS-D) is a chronic functional bowel disease with no clear diagnostic markers and no satisfactory treatment strategies. In recent years, the importance of intestinal microstructure and function in IBS-D has been emphasized. However, the intestinal tissue proteomics of IBS-D patients has not been analyzed. Here, we systematically analyzed the molecule profiling of the intestinal tissues in IBS-D patients through tandem mass tag (TMT)-based proteomics for the first time, aiming to reveal the pathogenesis and provide evidence for diagnosis and treatment of IBS-D. Five IBS-D patients and five healthy subjects were selected, biopsy tissue samples from the junction of sigmoid and rectum were analyzed by TMT proteomics. Differentially expressed proteins were obtained and bioinformatics analysis was performed. Furthermore, parallel reaction monitoring (PRM) and q-PCR detection were applied to validate the differentially expressed proteins. Eighty differentially expressed proteins were screened, 48 of which were up-regulated and 32 were down-regulated (fold change >1.2, P < 0.05). Bioinformatics analysis showed that these proteins were significantly enriched in the nutrient ingestion pathways which are related to immune molecules. SELENBP1, VSIG2, HMGB1, DHCR7, BCAP31 and other molecules were significantly changed. Our study revealed the underlying mechanisms of IBS-D intestinal dysfunction. SIGNIFICANCE: Irritable bowel syndrome with diarrhea (IBS-D) is a worldwide chronic intestinal disease with no definite diagnostic markers. It is still a challenge to accurately locate the pathogenesis of patients for appropriate treatment strategy. Established proteomics studies of IBS-D are only based on urine, blood, or tissue samples from animals. Our study was the first TMT proteomics analysis on intestinal biopsy tissues of patients with IBS-D, which revealed the changes of molecular spectrum of actual intestinal conditions in patients with IBS-D. Some important molecules and signaling pathways have been found abnormal in our study, which were related with nutrient uptake. They not only provided preliminary clues for low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance, an unsolved conundrum of IBS-D, but also revealed obscure problems of protein, lipid, and other nutrients ingestion in IBS-D patients. Some of these differentially expressed molecules have been preliminarily verified, and will may be potential candidate molecules for diagnostic markers of IBS-D.

Sestrin2 protects dendritic cells against endoplasmic reticulum stress-related apoptosis induced by high mobility group box-1 protein.

Sestrin2 (SESN2) is a highly evolutionary conserved protein and involved in different cellular responses to various stresses. However, the potential function of SESN2 in immune system remains unclear. The present study was designed to test whether dendritic cells (DCs) could express SESN2, and investigate the underlying molecular mechanism as well as its potential significance. Herein, we firstly reported that SESN2 was expressed in DCs after high mobility group box-1 protein (HMGB1) stimulation and the apoptosis of DCs was obviously increased when SESN2 gene silenced by siRNA. Cells undergone SESN2-knockdown promoted endoplasmic reticulum (ER) stress (ERS)-related cell death, markedly exacerbated ER disruption as well as the formation of dilated and aggregated structures, and they significantly aggravated the extent of ERS response. Conversely, overexpressing SESN2 DCs markedly decreased apoptotic rates and attenuated HMGB1-induced ER morphology fragment together with inhibition of ERS-related protein translation. Furthermore, sesn2-/--deficient mice manifested increased DC apoptosis and aggravated ERS extent in septic model. These results indicate that SESN2 appears to be a potential regulator to inhibit apoptotic ERS signaling that exerts a protective effect on apoptosis of DCs in the setting of septic challenge.

miR-145-5p restrained cell growth, invasion, migration and tumorigenesis via modulating RHBDD1 in colorectal cancer via the EGFR-associated signaling pathway.

miR-145-5p has been reported to be downregulated and described functioning as a tumor suppressive gene in colorectal cancer (CRC), yet its detailed regulatory function and mechanism in malignant progression of the disease have not been thoroughly understood. In our study, miR-145-5p and rhomboid domain containing 1 (RHBDD1) in CRC tissues and cells were examined by qRT-PCR and western blot. MTT, colony formation, wound healing, Transwell invasion, and flow cytometry assays were performed to evaluate the malignant phenotypes of CRC cells. Xenograft tumor, qRT-PCR, and western blot assays were applied to validate the roles and mechanism of miR-145-5p in CRC in vivo. The interaction between miR-145-5p and RHBDD1 was investigated by luciferase reporter assay and western blot. The changes of the EGFR/Raf/MEK/ERK pathway were detected by western blot. We found miR-145-5p was lowly expressed and low miR-145-5p predicted poor prognosis in CRC, while RHBDD1 was greatly enhanced in CRC cells and tissues. RHBDD1 silencing resulted in inhibiting cell proliferative, invasive, and migratory potentials as well as elevating apoptotic ones in CRC cells. miR-145-5p was inversely related with RHBDD1 expression in CRC tissues. miR-145-5p was found to directly bind to RHBDD1 and restrained its expression in CRC cells. miR-145-5p overexpression repressed CRC cell proliferation, invasion, migration and induced apoptosis, and these effects were reversed by RHBDD1 upregulation. Moreover, in CRC xenograft tumor, its growth was impeded by miR-145-5p via suppressing RHBDD1. Furthermore, miR-145-5p inhibited the expression of EGFR, p-MEK1/2 and p-ERK1/2, in vitro and in vivo by targeting RHBDD1. In conclusion, our study revealed that miR-145-5p overexpression inhibited tumorigenesis in CRC by downregulating RHBDD1 via suppressing the EGFR-associated signaling pathway (EGFR/Raf/MEK/ERK cascades).

RETRACTED: Physcion 8-O-ß-glucopyranoside induced ferroptosis via regulating miR-103a-3p/GLS2 axis in gastric cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Editor-in-Chief and the authors. The journal was initially contacted by the corresponding author to request the retraction of the article because the author claimed that part of the paper was outsourced to a third-party company who offered them the "wrong picture". During the investigation, the Editor became aware of allegations about this article on Pubpeer. Figure 7E is similar to Figure 7F from the article published by Xiaoping Pan, Chen Wang, Yan Li, Lida Zhu and Ti Zhang in Life Sciences, 214, (2018) 124-135 https://doi.org/10.1016/j.lfs.2018.10.064, a similar portion of Figure 6D from the article published by Qiang Wang, Yi Yan, Jie Zhang, Peng Guo, Yuqing Xing, Yong Wang, Fawei Qin and Qingyun Zeng in Biomedicine & Pharmacotherapy, 104, (2018) 28-35 https://doi.org/10.1016/j.biopha.2018.05.013, portions of Figure 6C from the article published by Jun Zou, Yamei Wang, Mingdi Liu, Xiushu Huang, Wenjian Zheng, Qian Gao, Haijing Wang in Cell Biochemistry and Function, 36, (2018) 303-311 https://doi.org/10.1002/cbf.3349, portions of Figure 8C from the article published by Kaili Liu, Hui Gao, Qiaoyun Wang , Longyuan Wang, Bin Zhang , Zhiwu Han, Xuehong Chen, Mei Han, and Mingquan Gao in Cancer Science, 109, (2018) 1369-1381 https://doi.org/10.1111/cas.13575, portions of Figure 8D of the article published by Xiangyang Dou, Meihua Wang, Tao Zhang and Jiapei Yao in The Anatomical Record, 303, (2020) 3117-3128 https://doi.org/10.1002/ar.24324, portions of Figure 6F from the article published by Xuezhu Lin, Mingquan Gao, Ailing Zhang, Jingjie Tong, Xiaoyi Zhang, Quanzhong Su, Zhihong Yang, Hui Gao and Guohui Jiang in Life Sciences 239, (2019) 117074 https://doi.org/10.1016/j.lfs.2019.117074, portions of 6F from the article published by Luping Wang, Lu Yun, Xiaojun Wang, Liying Sha, Luning Wang, Yingying Sui and Hui Zhang in Life Sciences, 218, (2019) 16-24 https://doi.org/10.1016/j.lfs.2018.12.023, and portions of Figure 7F from the article published by Dong Li, Xiaoyan Li , Genqu Li , Yan Meng , Yanghong Jin , Shuang Shang , Yanjie Li in Life Sciences, 216, (2019) 259-270 https://doi.org/10.1016/j.lfs.2018.11.032. The journal requested the authors to provide the raw data. However, the authors were not able to fulfill this request and therefore the Editor-in-Chief has decided to retract the article.

Role of dendritic cells in the host response to biomaterials and their signaling pathways.

Strategies to enhance, inhibit, or qualitatively modulate immune responses are important for diverse biomedical applications such as vaccine adjuvant, drug delivery, immunotherapy, cell transplant, tissue engineering, and regenerative medicine. However, the clinical efficiency of these biomaterial systems is affected by the limited understanding of their interaction with complex host microenvironments, for example, excessive foreign body reaction and immunotoxicity. Biomaterials and biomedical devices implanted in the body may induce a highly complicated and orchestrated series of host responses. As macrophages are among the first cells to infiltrate and respond to implanted biomaterials, the macrophage-mediated host response to biomaterials has been well studied. Dendritic cells (DCs) are the most potent antigen-presenting cells that activate naive T cells and bridge innate and adaptive immunity. The potential interaction of DCs with biomaterials appears to be critical for exerting the function of biomaterials and has become an important, developing area of investigation. Herein, we summarize the effects of the physicochemical properties of biomaterials on the immune function of DCs together with their receptors and signaling pathways. This review might provide a complete understanding of the interaction of DCs with biomaterials and serve as a reference for the design and selection of biomaterials with particular effects on targeted cells. STATEMENT OF SIGNIFICANCE: Biomaterials implanted in the body are increasingly applied in clinical practice. The performance of these implanted biomaterials is largely dependent on their interaction with the host immune system. As antigen-presenting cells, dendritic cells (DCs) directly interact with biomaterials through pattern recognition receptors (PRRs) recognizing "biomaterial-associated molecular patterns" and generate a battery of immune responses. In this review, the physicochemical properties of biomaterials that regulate the immune function of DCs together with their receptors and signaling pathways of biomaterial-DC interactions are summarized and discussed. We believe that knowledge of the interplay of DC and biomaterials may spur clinical translation by guiding the design and selection of biomaterials with particular effects on targeted cell for tissue engineering, vaccine delivery, and cancer therapy.