Identification of TFR2 as a novel ferroptosis­related gene that serves an important role in prognosis and progression of triple­negative breast cancer.

Effective targeted therapeutic strategies for triple-negative breast cancer (TNBC), the most malignant subtype of breast cancer, are currently lacking. Ferroptosis has been reported to be associated with the onset and advancement of various cancer types, including TNBC. However, there are limited studies on the correlation between TNBC and ferroptosis-related genes. In addition, the potential biomarkers of ferroptosis in TNBC need further investigation. The present study aimed to assess the prognostic role of a novel ferroptosis-related gene signature in the context of TNBC. The signature was established utilizing The Cancer Genome Atlas dataset. This three-gene model [transferrin receptor 2 (TFR2), regulator of G protein signaling 4 and zinc finger protein 36] was developed utilizing least absolute shrinkage and selection operator regression analysis and demonstrated satisfactory predictive performance in TNBC. The area under the curve values of the receiver operating characteristic curves in this model concerning the 1-, 2- and 3-year survival prediction were 0.721, 0.840 and 0.856, respectively. The predictive performance of the model was verified using the TNBC dataset GSE25307. Gene set enrichment analysis (GSEA) demonstrated the enrichment of genes in the low-risk group in a number of important metabolic pathways. Single-sample GSEA demonstrated a variation in the expression levels of immune checkpoint molecules between the high- and low-risk groups. The inhibitory impact of TFR2 knockdown on the proliferative capacity of TNBC cells was verified through in vitro experiments. The data also demonstrated that TFR2 knockdown facilitated the ferroptosis of TNBC cells. Additional assessments indicated that the effects of TFR2 knockdown were partially reversed upon treatment with the ferroptosis inhibitor ferrostatin-1. In conclusion, in the present study, a novel and accurate ferroptosis-related predictive signature was established for TNBC with potential future clinical applications. To the best of our knowledge, the present study is the first to report that TFR2 regulated ferroptosis in TNBC cells in vitro.

Histone deacetylation-regulated cell surface Siglec-7 expression promoted megakaryocytic maturation and enhanced platelet-like particle release.

BACKGROUND: Functioning as important hematologic cells for hemostasis, wound healing and immune defense platelets are produced before being released into the blood by cytoplasmic fragmentation at the end of the megakaryocyte (MK) differentiation, during which the involvement of both apoptosis and autophagy has been reported. Inhibitory sialic acid-binding immunoglobulin-like lectin-7 gene (Siglec-7) can be expressed on platelets and induce apoptosis on activation for uncharacterized function. OBJECTIVE: We aimed to investigate the regulatory mechanism for Siglec-7 activation along MK differentiation and its physiologic role during the MK maturation and platelet formation. METHODS: By using 2 well-established MK differentiation models (HEL and K562) and human primary CD34+ cell, we examined the upregulations of transcript and protein levels of Siglec-7 during MK differentiation, and the effect of Siglec-7 surface presence on MK differentiation and platelet-like particles (PLPs) release. RESULTS: We show that both transcripts and surface Siglec-7 were elevated during MK differentiation, and the histone deacetylase 1 (HDAC1) acted as a negative regulator for Siglec-7 activation. By increasing Siglec-7 surface expression, we found that increased presence of Siglec-7 not only enhanced MK maturation but also the release of PLPs by activating caspase 3-dependent signaling, as evidenced in the observation of more CD41, polyploidy, and platelet factor 4 transcript formations. CONCLUSION: In this study, we demonstrated that Siglec-7 activation was subjected to epigenetic regulation, and the resulting induced expression of surface Siglec-7 played an important regulatory role in promoting MK differentiation, maturation, and PLP formation.

Bioinformatics analyses of differentially expressed genes associated with spinal cord injury: A microarray-based analysis in a mouse model.

Gene spectrum analysis has shown that gene expression and signaling pathways change dramatically after spinal cord injury, which may affect the microenvironment of the damaged site. Microarray analysis provides a new opportunity for investigating diagnosis, treatment, and prognosis of spinal cord injury. However, differentially expressed genes are not consistent among studies, and many key genes and signaling pathways have not yet been accurately studied. GSE5296 was retrieved from the Gene Expression Omnibus DataSet. Differentially expressed genes were obtained using R/Bioconductor software (expression changed at least two-fold; P < 0.05). Database for Annotation, Visualization and Integrated Discovery was used for functional annotation of differentially expressed genes and Animal Transcription Factor Database for predicting potential transcription factors. The resulting transcription regulatory protein interaction network was mapped to screen representative genes and investigate their diagnostic and therapeutic value for disease. In total, this study identified 109 genes that were upregulated and 30 that were downregulated at 0.5, 4, and 24 hours, and 3, 7, and 28 days after spinal cord injury. The number of downregulated genes was smaller than the number of upregulated genes at each time point. Database for Annotation, Visualization and Integrated Discovery analysis found that many inflammation-related pathways were upregulated in injured spinal cord. Additionally, expression levels of these inflammation-related genes were maintained for at least 28 days. Moreover, 399 regulation modes and 77 nodes were shown in the protein-protein interaction network of upregulated differentially expressed genes. Among the 10 upregulated differentially expressed genes with the highest degrees of distribution, six genes were transcription factors. Among these transcription factors, ATF3 showed the greatest change. ATF3 was upregulated within 30 minutes, and its expression levels remained high at 28 days after spinal cord injury. These key genes screened by bioinformatics tools can be used as biological markers to diagnose diseases and provide a reference for identifying therapeutic targets.

Biomarker identification and trans-regulatory network analyses in esophageal adenocarcinoma and Barrett's esophagus.

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated. AIM: To explore the transcriptome changes in the progression from normal esophagus (NE) to BE and EAC. METHODS: Two datasets from the Gene Expression Omnibus (GEO) in NCBI Database (https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes (DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets. RESULTS: In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors (DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs, E2F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1A1 could discriminate EAC from NE tissue, while REG1A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer. CONCLUSION: After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.

Application of Gelatin Sponge Impregnated with a Mixture of 3 Drugs to Intraoperative Nerve Root Block to Promote Early Postoperative Recovery of Lumbar Disc Herniation.

OBJECTIVE: To observe effect of application of gelatin sponge impregnated with a mixture of 3 drugs to intraoperative nerve root block to promote early postoperative recovery of lumbar disc herniation. METHODS: Retrospective analysis was performed of 265 patients with single-level lumbar disc herniation from January 2013 to October 2017. Patients were divided into intervention and control groups based on intraoperative application of gelatin sponge impregnated with a mixture of 3 drugs. All patients underwent unilateral minimally invasive surgical transforaminal lumbar interbody fusion. Clinical data, including bedridden period, postoperative hospital stay, visual analog scale scores for low back pain and leg pain, Japanese Orthopaedic Association score, postoperative satisfaction questionnaire results, and therapeutic effect, were collected. RESULTS: There were 136 cases in the intervention group and 129 cases in the control group. The intervention group had significantly shorter bedridden period and postoperative hospital stay than control group (P < 0.05). Visual analog scale scores for low back pain and leg pain at postoperative days 1-10 were significantly lower in the intervention group compared with control group (P < 0.05). The Japanese Orthopaedic Association score at postoperative day 6 and satisfaction at 72 hours postoperatively were significantly higher in the intervention group than in control group (P < 0.05). Clinical effect at postoperative day 6 was significantly better in the intervention group than control group (P < 0.05). CONCLUSIONS: Application of gelatin sponge impregnated with a mixture of 3 drugs to intraoperative nerve root block can significantly promote early postoperative recovery of lumbar disc herniation and has great short-term clinical efficacy.

Long Noncoding RNA CRNDE Promotes Multiple Myeloma Cell Growth by Suppressing miR-451.

It has been determined that long noncoding RNAs (lncRNAs) are identified as a potential regulatory factor in multiple tumors as well as multiple myeloma (MM). However, the role of colorectal neoplasia differentially expressed (CRNDE) in the pathogenesis of MM remains unclear. In this study, we found that the CRNDE expression level, in MM samples and cell lines, is higher than that in the control detected by real-time qPCR, which is also closely related to tumor progression and poor survival in MM patients. Knockdown of CRNDE significantly inhibits the proliferative vitality of MM cells (U266 and RPMI-8226), induces cell cycle arrest in the G0/G1 phase, and promotes apoptosis. After being transfected with siRNA, miR-451 expression observably increases. Bioinformatics analysis and luciferase assay reveal the interaction by complementary bonding between CRNDE and miR-451. Pearson's correlation shows that CRNDE is negatively correlated to miR-451 expression in human MM samples. Subsequently, miR-451 inhibitor rescues the inhibited tumorigenesis induced by CRNDE knockdown. Our study illustrates that lncRNA CRNDE induces the proliferation and antiapoptosis capability of MM by acting as a ceRNA or molecular sponge via negatively targeting miR-451, which could act as a novel diagnostic marker and therapeutic target for MM.

Use of micro-computed tomography to evaluate the effects of exercise on preventing the degeneration of articular cartilage in tail-suspended rats.

Space flight has been shown to induce bone loss and muscle atrophy, which could initiate the degeneration of articular cartilage. Countermeasures to prevent bone loss and muscle atrophy have been explored, but few spaceflight or ground-based studies have focused on the effects on cartilage degeneration. In this study, we investigated the effects of exercise on articular cartilage deterioration in tail-suspended rats. Thirty-two female Sprague-Dawley rats were randomly divided into four groups (n=8 in each): tail suspension (TS), tail suspension plus passive motion (TSP), tail suspension plus active exercise (TSA), and control (CON) groups. In the TS, TSP, and TSA groups, the rat hindlimbs were unloaded for 21 days by tail suspension. Next, the cartilage thickness and volume, and the attenuation coefficient of the distal femur were evaluated by micro-computed tomography (µCT). Histological analysis was used to assess the surface integrity of the cartilage, cartilage thickness, and chondrocytes. The results showed that: (1) the cartilage thickness on the distal femur was significantly lower in the TS and TSP groups compared with the CON and TSA groups; (2) the cartilage volume in the TS group was significantly lower compared with the CON, TSA, and TSP groups; and (3) histomorphology showed that the chondrocytes formed clusters where the degree of matrix staining was lower in the TS and TSP groups. There were no significant differences between any of these parameters in the CON and TSA groups. The cartilage thickness measurements obtained by µCT and histomorphology correlated well. In general, tail suspension could induce articular cartilage degeneration, but active exercise was effective in preventing this degeneration in tail-suspended rats.

[Clinical application of maxillary sinus augmentation, bone graft and simultaneously placement of implant with trephine bur].

OBJECTIVE: To introduce and evaluate the procedure and the effect of localized management of sinus floor (LMSF), bone graft and simultaneous implant placement with trephine bur in maxillary posterior region. METHODS: 24 patients without enough alveolar bone height received LMSF, bone grafting and implants placement were carried out simultaneously.The autogenous bone were harvested by trephine bur in situ. Patients were followed up after 1 week, 1, 3 and 6 month. RESULTS: There was no implant loose or lost and maxillary antritis. 6 months postoperatively, bone graft reformed to new bone seen in X-ray films, sinus floors were augmented and reached the requirements of dental implants. The implant osseointegrated tightly with new bone which was satisfactory to second-step prosthesis after implant placement of 6 months later. CONCLUSIONS: The method enlarges the indication of dental implants and avoids operation of harvesting autogenous bone in other site. It is simple and valuable to clinical application.