RP11-874J12.4 promotes oral squamous cell carcinoma tumorigenesis via the miR-19a-5p/EBF1 axis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) ranks as the fifth most frequent cancer worldwide, and the recurrence and migration of OSCC still pose large threats to patients. Long non-coding RNAs (lncRNAs) have recently emerged as crucial players in cancer development, and it is of great significance to understand the regulatory nexus of lncRNAs in OSCC. METHODS: Here, we identified a novel lncRNA, RP11-874J12.4, which is ectopically expressed in OSCC and facilitates OSCC. RESULTS: RP11-874J12.4 directly binds to and regulates miR-19a-5p. Interestingly, RP11-874J12.4 and miR-19a-5p form a negative regulatory loop that inhibits the expression of miR-19a-5p in OSCC. The expression of an oncogenic transcription factor, EBF1, is unleashed in OSCC due to the low expression of miR-19a-5p, which promotes the growth and migration of OSCC. CONCLUSION: Our data illustrate a regulatory axis of RP11-874J12.4/miR-19a-5P/EBF1 and an inhibitory loop with RP11-874J12.4 and miR-19a-5p. These data provide insights into the tumorigenesis of OSCC and the novel drug targets for OSCC.

Ginsenoside Rd Inhibits Glioblastoma Cell Proliferation by Up-Regulating the Expression of miR-144-5p.

miR-144-5p exhibits anti-tumor activities in various cancers. Although treatment for glioblastoma has progressed rapidly, novel targets for glioblastoma are insufficient, particularly those used in precision medicine. In the current study, we found that ginsenoside Rd reduced the proliferation and migration of glioblastoma cells. Ginsenoside Rd up-regulated the tumor-suppressive miR-144-5p in glioblastoma cells. Moreover, Toll-like receptor 2, which is a target of miR-144-5p, was down-regulated. After inhibition of miR-144-5p, the effect of Ginsenoside Rd on proliferation inhibition and down-regulation of Toll-like receptor 2 was reduced. These data demonstrated the ginsenoside Rd/miR-144-5p/Toll-like receptor 2 regulatory nexus that controls the glioblastoma pathogenesis of glioblastoma. Our work provided novel targets for glioblastoma diagnosis and treatment.

A periodontal tissue regeneration strategy via biphasic release of zeolitic imidazolate framework-8 and FK506 using a uniaxial electrospun Janus nanofiber.

Guided tissue regeneration (GTR) strategies are an effective approach to repair periodontal defects by using GTR membranes. However, commercial GTR membranes still have limitations in periodontal tissue regeneration owing to lack of antibacterial and osteogenic properties. The development of novel Janus nanofibers with biphasic release characteristics based on the therapeutic needs of GTR is essential to tackle this issue. Here, we developed a multifunctional Janus nanofiber via uniaxial electrospinning, with zeolitic imidazolate framework-8 nanoparticle (ZIF-8 NP) loading in the hydrophilic polyvinylpyrrolidone (PVP) part and FK506 embedding in the hydrophobic polycaprolactone (PCL) part. The release of Zn2+ conformed to the Ritger-Peppas kinetics which could effectively prevent bacterial infection, and the release profile of FK506 was fitted to a first-order equation which could provide persistent osteogenic stimulation for osteogenesis. The periodontal tissue regeneration data from a rat periodontitis model revealed that the multifunctional electrospun Janus nanofibers could be used as an effective bioplatform to restore alveolar bone impairment, compared with the control group. In summary, the Janus nanofibers with biphasic release characteristics quickly exert antibacterial function as well as continuously provide a microenvironment beneficial to the osteogenesis process, demonstrating its great potential for GTR treatment in dental clinic applications.

ZIF-8 modified multifunctional injectable photopolymerizable GelMA hydrogel for the treatment of periodontitis.

Periodontitis is a chronic inflammatory disease caused by plaque that leads to alveolar bone resorption. In the treatment of periodontitis, it is necessary to reduce the bacterial load and promote alveolar bone regeneration. In this study, zeolitic imidazolate framework-8 (ZIF-8) is used in the treatment of periodontitis, and an injectable photopolymerizable ZIF-8/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z) is constructed. We confirm that ZIF-8 nanoparticles are successfully loaded into GelMA, which demonstrates fluidity and photopolymerizability. GelMA-Z continuously releases Zn2+ and shows good cytocompatibility. In vitro, GelMA-Z can effectively upregulate the expression of osteogenesis-related genes and proteins, increase alkaline phosphatase activity, promote extracellular matrix mineralization by rat bone mesenchymal stem cells, and exert an obvious antibacterial effect against Porphyromonas gingivalis. In vivo, GelMA-Z reduces the bacterial load, relieves inflammation and promotes alveolar bone regeneration in a rat model. The above results show that GelMA-Z has potential prospects in the treatment of periodontitis. STATEMENT OF SIGNIFICANCE: Various methods have been explored for the treatment of periodontitis. However, current regiments have difficulty achieving ideal alveolar bone regeneration. In this study, we constructed a zeolitic imidazolate framework-8 (ZIF-8)/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z). (1) The injectable and photopolymerizable GelMA-Z showed biocompatibility in vitro and in vivo. (2) GelMA-Z continually released zinc ions to promote the osteogenic differentiation of bone mesenchymal stem cells and kill bacteria in vitro. (3) In a rat model, the GelMA-Z pregel solution was used to fill the periodontal pocket and then crosslinked by UV exposure. GelMA-Z can stably remain in the periodontal pocket to reduce the bacterial load, relieve inflammation and promote alveolar bone regeneration. In conclusion, GelMA-Z has great potential for use in the treatment of periodontitis, especially in promoting alveolar bone regeneration.

Expression of miR-1304 in patients with esophageal carcinoma and risk factors for recurrence.

BACKGROUND: Esophageal carcinoma is a malignant gastrointestinal tumor with a very poor prognosis. MicroRNA (miR)-1304 is a newly discovered non-coding RNA, which shows differential expression in other cancers, and its clinical value in esophageal carcinoma remains unclear. AIM: To explore the expression of miR-1304 in patients with esophageal carcinoma and its clinical value. METHODS: The expression of miR-1304 in patients with esophageal carcinoma was analyzed based on the data on miR in esophageal carcinoma downloaded from The Cancer Genome Atlas database. Quantitative real-time polymerase chain reaction was adopted to determine the expression of miR-1304 in the tissues and serum of patients. The clinical diagnostic value of miR-1304 and independent factors for recurrence and prognosis of esophageal carcinoma were then analyzed. The potential target genes of miR-1304 were predicted, and then analyzed based on gene ontology, Kyoto Encyclopedia of Genes, and Genomes, and protein-protein interaction. RESULTS: The expression of miR-1304 in the tissues and serum of patients with esophageal carcinoma increased, and was also increased according to the database. Patients with high expression of miR-1304 suffered increased rates of tumor ≥ 3 cm, low differentiation and stage II + III. miR-1304 had a diagnostic value in identifying esophageal carcinoma, tumor size, differentiation and TNM stage. Tumor size, differentiation, TNM stage, and miR-1304 were independent risk factors for recurrence of esophageal carcinoma, and they had certain predictive and diagnostic value for the recurrence of esophageal carcinoma. Seventy-eight patients showed a 3-year survival rate of 38.46%, and patients with high expression of miR-1304 had a relatively lower survival rate. Multivariate analysis revealed that tumor size, differentiation, recurrence and miR-1304 were independent factors for the prognosis of patients. MiRTarBase, miRDB, and Targetscan predicted 20 target genes in total. Gene ontology enrichment analysis found 18 functions with a P < 0.05, and Kyoto Encyclopedia of Genes, and Genomes analysis found 11 signal pathways with a P < 0.05. String analysis of protein co-expression found 269 relationship pairs, of which co-expression with epidermal growth factor was the most common. CONCLUSION: miR-1304 can be used as a potential indicator for the diagnosis and recurrence of esophageal carcinoma and for survival of patients with this disease.

Exosomal proteome from the serum, bone marrow, and palm and toe pustular skin tissues of a single patient with SAPHO syndrome.

Exosome proteomic analysis may reveal differentially abundant proteins that are of significance for clarifying the pathogenesis of SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) syndrome. Exosomes were isolated from the serum, bone marrow and skin tissue of the palm and toe pustular areas in a unique patient with SAPHO syndrome. The exosomes were not different from those of healthy subjects in size (114.1 ± 73.7 nm) or morphology. Label-free exosome proteomic analysis identified 198 more abundant proteins and 183 less abundant compared with those of healthy subjects. Gene ontology enrichment analysis revealed that these proteins were involved in binding with a variety of biological molecules and participated in biological processes related to autoimmunity or inflammation. A total of 243 KEGG (Kyoto Encyclopedia of Gene and Genomes) pathways were enriched, of which 43 were related to immune function. It was speculated that five differentially abundant proteins, Mitogen-activated protein kinase 1 (MAPK1/MK01), Tyrosine protein kinase (SYK), Integrin beta-3 (ITB3), Serine/threonine-protein phosphatase 2a catalytic subunit alpha isoform (PP2AA) and Serine/threonine-protein phosphatase 2a 65 kDa regulatory subunit A beta isoform (2AAB), associated with multiple KEGG pathways, forms an interaction network that may be involved in the occurrence, development and prognosis of SAPHO syndrome. SIGNIFICANCE: Exosomes of SAPHO syndrome patient were not significantly different from those of healthy subjects in size and morphology. Label-free proteomic analysis of exosomal proteins in patient with SAPHO syndrome speculated 5 proteins MAPK1, SYK, ITB3, PP2AA and 2AAB, which may be involved in the occurrence, development and prognosis of SAPHO syndrome by binding with other biological molecules. It is speculated for the first time that proteins Histone H2A type 1-J and Histone H4 were related to SAPHO syndrome. Clinic relevance. Exosome proteomics can suggest novel pathological data in patients with SAPHO.

Bone formation promoted by bone morphogenetic protein-2 plasmid-loaded porous silica nanoparticles with the involvement of autophagy.

Gene therapy is one of the most common and effective ways for the regeneration of defective bone tissue, but even highly efficient gene delivery vectors are insufficient. In this study, bone morphogenetic protein-2 plasmid (pBMP-2) was encapsulated by polyethylenimine-modified porous silica nanoparticles (PPSNs), which were synthesized via an ethyl ether emulsion method. Owing to the high specific surface area and high absorption characteristics, low cytotoxicy PPSNs can efficiently load and protect pBMP-2. The resulting PPSN/pBMP-2 can transfect MC3T3-E1 cells effectively to promote osteogenic differentiation and increase calcium deposition in vitro. Interestingly, the mass of calcium deposition nodules decreased dur to the presence of an autophagy inhibitor, demonstrating that PPSNs stimulated the autophagy pathway. Because of their excellent biocompatibility, high transfection efficiency, and ability to stimulate autophagy, the as-prepared PPSN/pBMP-2 could efficiently transfect local cells in a defect area in vivo. Micro-computed tomography and histological images demonstrated that PPSN/pBMP-2 could efficiently promote new bone formation in a 5 mm sized rat calvarial defect model. Taken together, our newly synthesized PPSNs could efficiently carry pBMP-2 and deliver it to the target cells as well as stimulating the autophagy pathway, resulting in significant osteogenic differentiation and bone regeneration.

Comprehensive multi-omics analysis identified core molecular processes in esophageal cancer and revealed GNGT2 as a potential prognostic marker.

BACKGROUND: Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world. Although a series of studies on esophageal cancer have been reported, the molecular pathogenesis of the disease remains elusive. AIM: To investigate comprehensively the molecular process of esophageal cancer. METHODS: Differential expression analysis was performed to identify differentially expressed genes (DEGs) in different stages of esophageal cancer from The Cancer Genome Atlas data. Exacting gene interaction modules were generated, and hub genes in the module interaction network were found. Further, through survival analysis, methylation analysis, pivot analysis, and enrichment analysis, some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer. RESULTS: A total of 7457 DEGs and 14 gene interaction modules were identified. These module genes were significantly involved in the positive regulation of protein transport, gastric acid secretion, insulin-like growth factor receptor binding, and other biological processes as well as p53 signaling pathway, epidermal growth factor signaling pathway, and epidermal growth factor receptor signaling pathway. Transcription factors (including hypoxia inducible factor 1A) and non-coding RNAs (including colorectal differentially expressed and hsa-miR-330-3p) that significantly regulate dysfunction modules were identified. Survival analysis showed that G protein subunit gamma transducin 2 (GNGT2) was closely related to survival of esophageal cancer. DEGs with strong methylation regulation ability were identified, including SST and SH3GL2. Furthermore, the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction, and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines. Moreover, cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines. CONCLUSION: This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.

An injectable and thermosensitive hydrogel: Promoting periodontal regeneration by controlled-release of aspirin and erythropoietin.

Periodontitis is an inflammatory disease induced by complex interactions between host immune system and plaque microorganism. Alveolar bone resorption caused by periodontitis is considered to be one of the main reasons for tooth loss in adults. To terminate the alveolar bone resorption, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. In this study, chitosan (CS), ß-sodium glycerophosphate (ß-GP), and gelatin were used to prepare an injectable and thermosensitive hydrogel, which could continuously release aspirin and erythropoietin (EPO) to exert pharmacological effects of anti-inflammation and tissue regeneration, respectively. The releasing profile showed that aspirin and EPO could be continuously released from the hydrogels, which exhibited no toxicity both in vitro and in vivo, for at least 21 days. Immunohistochemistry staining and micro-CT analyses indicated that administration of CS/ß-GP/gelatin hydrogels loaded with aspirin/EPO could terminate the inflammation and recover the height of the alveolar bone, which is further confirmed by histological observations. Our results suggested that CS/ß-GP/gelatin hydrogels are easily prepared as drug-loading vectors with excellent biocompatibility, and the CS/ß-GP/gelatin hydrogels loaded with aspirin/EPO are quite effective in anti-inflammation and periodontium regeneration, which provides a great potential candidate for periodontitis treatment in the dental clinic. Statement of Significance To terminate the alveolar bone resorption caused by periodontitis, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. Here, (1) the chitosan (CS)/ß-sodium glycerophosphate/gelatin hydrogels loaded with aspirin/erythropoietin (EPO) can form at body temperature in 5 min with excellent biocompatibility in vitro and in vivo; (2) The faster release of aspirin than EPO in the early stage is beneficial for anti-inflammation and provides a microenvironment for ensuring the regeneration function of EPO in the following step. In vivo experiments revealed that the hydrogels are effective in the control of inflammation and regeneration of the periodontium. These results indicate that our synthesized hydrogels have a great potential in the future clinical application.

Microwave-Assisted Heating Method toward Multicolor Quantum Dot-Based Phosphors with Much Improved Luminescence.

Solid-state highly photoluminescent quantum dot (QD)-based phosphors attract great scientific interests as color converters because of an increasing demand for white-light-emitting devices. Herein, a microwave-assisted heating method is presented to fabricate multicolor QD-based phosphors within 30 s through microwave-assisted heating of the mixture of QDs and sodium silicate aqueous solution. In the composites, the formed cross-linked networks not only play as a matrix to prevent QD aggregation in solid state but also cause the variation of the refractive index around QDs and the QD surface optimization, which contributes to good stabilities and twice enhancement in photoluminescence quantum yields (69%) compared with the initial QD aqueous solution (33%). Using the QD-based phosphors as color conversion layers, white-light-emitting diodes were realized with controllable color temperature, high color purity, and high color-rendering index (90.3), which show a great potential in display and illumination. Furthermore, the luminescence lifetime of the QD-based phosphors is less than 25 ns. The potential application of the QD-based phosphors in visible light communication was also demonstrated, with the modulation bandwidth achieving 42 MHz.