The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.

Osteosarcoma (OS) is one of the most aggressive bone tumors worldwide. Emerging documents have shown that long noncoding RNAs (lncRNAs) elicit crucial regulatory functions in the process of tumorigenesis. LncRNA DLGAP1-AS2 is recognized as a regulator in several types of cancers, but its biological functions and molecular mechanisms in OS remain to be elucidated. RT-qPCR and In situ hybridization (ISH) were used to evaluate DLGAP1-AS2 expression in OS samples. Western blotting was used for the measurement of the protein levels of hexokinase 2 (HK2) and epithelial-mesenchymal transition (EMT)-related markers. The proliferation of OS cells was determined using a CCK-8 assay and EdU assay. TUNEL assay and flow cytometry were performed to assess OS cell apoptosis. Glucose metabolism in vitro assays were used. The binding relations among miR-451a, HK2, and DLGAP1-AS2 were validated by luciferase reporter assay. The cellular distribution of DLGAP1-AS2 in OS cells was determined by FISH and subcellular fractionation assays. Mouse xenograft models were established to perform the experiments in vivo. We found that DLGAP1-AS2 expression was upregulated in OS tissues and cells. Downregulation of DLGAP1-AS2 expression suppressed the malignancy of OS cells by restraining cell proliferation, the EMT process, invasiveness, migration, and aerobic glycolysis and accelerating apoptotic behaviors. Of note, silenced DLGAP1-AS2 restrained tumor growth and metastasis in vivo. However, DLGAP1-AS2 overexpression accelerated the progression of OS. We further found that DLGAP1-AS2 upregulation was induced by hypoxia and low glucose. Additionally, DLGAP1-AS2 bound to miR-451a to upregulate HK2 expression. Rescue assays revealed that the DLGAP1-AS2/miR-451a/HK2 axis contributed to OS cell malignancy by promoting aerobic glucose metabolism. Overall, these findings revealed a new regulatory pathway where DLGAP1-AS2 upregulated HK2 expression by sponging miR-451a to accelerate OS development.

A rare left ventricular cardiac myxoma mimicking fibroma.

BACKGROUND: In most cases, it is not difficult to differentiate common left ventricular (LV) cardiac myxomas from fibromas because they are different disease entities and have different imaging findings. Herein, we present a case of a tumor with histological characteristics of a LV cardiac myxoma even though its imaging and macroscopical views were similar to that of fibroma. CASE PRESENTATION: A 65-year-old woman was admitted to the hospital with chest tightness and palpitations which persisted for 2 years. Transthoracic echocardiogram and transesophageal echocardiography revealed a 23 mm × 8 mm, polyp-like-shaped, homogeneous, firm, solitary, mobile and solitary LV mass, which protruded into the left atrium during systole, resulting in mild mitral regurgitation. LV contrast-enhanced echocardiography revealed that there was little contrast agent filling in the LV mass. To further clarify the nature of the mass, non-enhanced and contrast-enhanced coronary computed tomography (CT) angiograms showed a 19 mm × 8 mm relatively homogeneous low density with punctate calcifications mass and no significant enhancement. Thus, we preoperatively diagnosed her condition as a LV fibroma and performed excision of the tumor under cardiopulmonary by-pass by using port-access approach through right mini-thoracotomy. The postoperative pathological diagnosis of the tumor was in fact a LV myxoma. CONCLUSIONS: LV cardiac myxomas mimicking fibroma makes diagnosis difficult, and sonographers should be aware of this imaging changes.

LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-ß/SMAD Signaling Pathway and Upregulating SSH2 Expression.

Osteosarcoma (OS), a frequent malignant tumor which mainly occurs in the bone. The roles of long noncoding RNAs (lncRNAs) have been revealed in cancers, including OS. LncRNA long intergenic non-protein coding RNA (LINC00174) has been validated as an oncogene in several cancers. However, the role of LINC00174 in OS has not been explored. In our research, loss-of-function assays were conducted to explore the function of LINC00174 in OS cells. Then, we explored the downstream pathway of LINC00174 in OS cells. Bioinformatics, RNA pull-down and RIP experiments investigated the downstream mechanism of LINC00174 in OS cells. Finally, in vivo assays clarified the effect of LINC00174 on tumorigenesis. We found that LINC00174 was upregulated in OS tissues and cells. LINC00174 knockdown repressed OS cell growth. Mechanistically, LINC00174 knockdown suppressed the TGF-ß/SMAD pathway. LINC00174 interacted with miR-378a-3p, and slingshot protein phosphatase 2 (SSH2) 3'UTR was targeted by miR-378a-3p in OS cells. Rescue assays showed that SSH2 upregulation or miR-378a-3p inhibition counteracted the inhibitory effect of LINC00174 depletion in OS cell growth. Additionally, LINC00174 depletion suppressed tumor growth in mice. In conclusion, LINC00174 promotes OS cellular malignancy and tumorigenesis via the miR-378a-3p/SSH2 axis and the TGF-ß/SMAD pathway, which might provide a novel insight for OS treatment.

A novel mitochondrial-targeting fluorescent probe based on 1,4-dihydropyridine to visualize and monitor the viscosity of live cells and mice in vivo.

Cell viscosity is related to some diseases, such as diabetes, atherosclerosis, and Alzheimer's disease. These diseases can cause abnormal viscosity of the cell mitochondrial matrix. 1,4-Dihydropyridine (DHP) is an important organic compound with biological activity and is widely used in drug research. However, there are few studies on its optical properties, especially in the design of viscous fluorescent probes. In this study, a fluorescent probe for viscosity detection using 1,4-dihydropyridine as the fluorophore and indole iodide salt as the recognition group was designed and synthesized. The probe has the advantages of a deep-red emission, low cytotoxicity, good biocompatibility and excellent anti-interference ability. In addition, the probe also has the ability to target mitochondria and has been successfully applied to the detection of the viscosity response of HeLa cells and living mice, and has good clinical application potential.

Three-Dimensional Printing Strategies for Irregularly Shaped Cartilage Tissue Engineering: Current State and Challenges.

Although there have been remarkable advances in cartilage tissue engineering, construction of irregularly shaped cartilage, including auricular, nasal, tracheal, and meniscus cartilages, remains challenging because of the difficulty in reproducing its precise structure and specific function. Among the advanced fabrication methods, three-dimensional (3D) printing technology offers great potential for achieving shape imitation and bionic performance in cartilage tissue engineering. This review discusses requirements for 3D printing of various irregularly shaped cartilage tissues, as well as selection of appropriate printing materials and seed cells. Current advances in 3D printing of irregularly shaped cartilage are also highlighted. Finally, developments in various types of cartilage tissue are described. This review is intended to provide guidance for future research in tissue engineering of irregularly shaped cartilage.

Sustained Release of VEGF to Promote Angiogenesis and Osteointegration of Three-Dimensional Printed Biomimetic Titanium Alloy Implants.

Tumor resection and treatment of trauma-related regional large bone defects have major challenges in the field of orthopedics. Scaffolds that treat bone defects are the focus of bone tissue engineering. 3D printing porous titanium alloy scaffolds, prepared via electron beam melting technology, possess customized structure and strength. The addition of a growth factor coating to the scaffold introduces a specific form of biological activation. Vascular endothelial growth factor (VEGF) is key to angiogenesis and osteogenesis in vivo. We designed a porous titanium alloy scaffold/thermosensitive collagen hydrogel system, equipped with VEGF, to promote local osseointegration and angiogenesis. We also verified the VEGF release via thermosensitive collagen and proliferation and induction of the human umbilical vein endothelial cells (HUVECs) via the composite system in vitro. In vivo, using microscopic computed tomography (Micro-CT), histology, and immunohistochemistry analysis, we confirmed that the composite scaffold aids in angiogenesis-mediated bone regeneration, and promotes significantly more bone integration. We also discovered that the composite scaffold has excellent biocompatibility, provides bioactive VEGF for angiogenesis and osteointegration, and provides an important theoretical basis for the restoration of local blood supply and strengthening of bone integration.

An Update on the Emerging Role of Visfatin in the Pathogenesis of Osteoarthritis and Pharmacological Intervention.

Osteoarthritis (OA) is one of the most common degenerative joint diseases that affects millions of people worldwide, mainly the aging population. Despite numerous published reports, little is known about the pathology of this disease, and no feasible treatment plan exists to stop OA progression. Recently, extensive basic and clinical studies have shown that adipokines play a key role in OA development. Moreover, some drugs associated with adipokines have shown chondroprotective and anti-inflammatory effects on OA. Visfatin has been shown to play a detrimental role in the progression of OA. It increases the production of matrix metalloproteinases and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), induces the production of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, affects the differentiation of mesenchymal stem cells to adipocytes, and induces osteophyte formation by inhibiting osteoclastogenesis. Although some side effects of chemical visfatin inhibitors have been reported, they were shown to be successful in the treatment of diabetes, cancer, and other diseases that can utilize Chinese herbs, further suggesting that similar therapeutic strategies could be used in OA prevention and treatment. Here, we describe the pathophysiological mechanism of visfatin in OA and discuss some potential pharmacological interventions using Chinese herbs.

Study of Osteoarthritis-Related Hub Genes Based on Bioinformatics Analysis.

Osteoarthritis (OA) is a common cause of morbidity and disability worldwide. However, the pathogenesis of OA is unclear. Therefore, this study was conducted to characterize the pathogenesis and implicated genes of OA. The gene expression profiles of GSE82107 and GSE55235 were downloaded from the Gene Expression Omnibus database. Altogether, 173 differentially expressed genes including 68 upregulated genes and 105 downregulated genes in patients with OA were selected based on the criteria of ∣log fold-change | >1 and an adjusted p value < 0.05. Protein-protein interaction network analysis showed that FN1, COL1A1, IGF1, SPP1, TIMP1, BGN, COL5A1, MMP13, CLU, and SDC1 are the top ten genes most closely related to OA. Quantitative reverse transcription-polymerase chain reaction showed that the expression levels of COL1A1, COL5A1, TIMP1, MMP13, and SDC1 were significantly increased in OA. This study provides clues for the molecular mechanism and specific biomarkers of OA.

Identification of biomarkers associated with synovitis in rheumatoid arthritis by bioinformatics analyses.

OBJECTIVES: Rheumatoid arthritis (RA) is the most common inflammatory arthritis in the world, but its underlying mechanism is still unclear. The present study aims to screen and verify the potential biomarkers of RA. METHODS: We searched the Gene Expression Omnibus (GEO) database for synovial expression profiling from different RA microarray studies to perform a systematic analysis. Functional annotation of differentially expressed genes (DEGs) was conducted, including GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) networks of the DEGs were constructed based on data from the STRING database. The expression levels of the hub genes in normal membranes and RA synovium were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot system. RESULTS: A total of 444 differential expression genes were identified, including 172 up-regulated and 272 down-regulated genes in RA synovium compared with normal controls. The top ten hub genes; protein tyrosine phosphatase receptor type C (PTPRC), LCK proto-oncogene (LCK), cell division cycle 20 (CDC20), Jun proto-oncogene (JUN), cyclin-dependent kinase 1 (CDK1), kinesin family member 11 (KIF11), epidermal growth factor receptor (epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), mitotic arrest deficient 2 like 1 (MAD2L1), and signal transducer and activator of transcription 1 (STAT1) were identified from the PPI network, and the expression level of VEGFA and EGFR was significantly increased in RA membranes (P<0.05). CONCLUSION: Our results indicate that the hub genes VEGFA and EGFR may have essential effects during the development of RA and can be used as potential biomarkers of RA.

Combined carbon photon and hydrogel therapy mediates the synergistic repair of full-thickness skin wounds.

OBJECTIVE: This study investigated the synergistic repair effects of Prontosan hydrogel and carbon photon therapy in a rat full-thickness wound model. METHODS: The wavelength distribution of the photon source was determined. Dehydration of the Prontosan hydrogel and fibroblast viability were analyzed following exposure to different durations of light exposure at different distances from the source. Indexes of wound healing in a full-thickness rat wound model were then determined in groups (n = 8 each) subjected to either no treatment, Prontosan treatment only, carbon photon therapy only, or a combination of the two treatments (synergistic group). RESULTS: Carbon photon exposure for 15 minutes at a distance of 20 cm from the wound was found to be optimal. Wound healing occurred faster in the synergistic group compared with the control and single-treatment groups. Growth factor secretion, granulation tissue formation, inflammation regulation, collagen deposition, and neovascularization were all higher in the synergistic group. CONCLUSIONS: Prontosan hydrogel combined with carbon photon therapy may provide an optimal environment for wound healing and serve as a novel physical approach to the treatment of wounds. However, the number of animals included in this study was relatively small and a larger study is required to confirm these findings.

Selection of Appropriate Wound Dressing for Various Wounds.

There are many factors involved in wound healing, and the healing process is not static. The therapeutic effect of modern wound dressings in the clinical management of wounds is documented. However, there are few reports regarding the reasonable selection of dressings for certain types of wounds in the clinic. In this article, we retrospect the history of wound dressing development and the classification of modern wound dressings. In addition, the pros and cons of mainstream modern wound dressings for the healing of different wounds, such as diabetic foot ulcers, pressure ulcers, burns and scalds, and chronic leg ulcers, as well as the physiological mechanisms involved in wound healing are summarized. This article provides a clinical guideline for selecting suitable wound dressings according to the types of wounds.

Overexpression of carboxypeptidase X M14 family member 2 predicts an unfavorable prognosis and promotes proliferation and migration of osteosarcoma.

BACKGROUND: Carboxypeptidase X, M14 family member 2 (CPXM2), has been associated with several human developmental disorders. However, whether CPXM2 is involved in oncogenesis or tumor progression remains unclear. Currently, the clinical relevance and function of CPXM2 in human osteosarcoma were investigated. MATERIALS AND METHODS: The expression of CPXM2 in osteosarcoma cell lines and tissues were explored by immunohistochemistry and western blotting assays. A eukaryotic expression plasmid was transfected into fetal osteoblast cells to overexpress CPXM2 and the endogenous CPXM2 in osteosarcoma cells was silenced through an RNA interference (RNAi) method transfection. These transfections were validated via western blotting, and the expression levels of several key molecules involved in the epithelial mesenchymal transition was also determined via western blotting. The expression levels of CPXM2 in a fetal osteoblast cell line with CPXM2 overexpressing and an osteosarcoma CPXM2-knockout cell line was confirmed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunofluorescence. The malignant phenotype of osteosarcoma cells was indicated by the cholecystokinin octapeptide, colony formation assay, scratch wound healing assay, and Transwell® migration assay. RESULTS: We found that CPXM2 was overexpressed in osteosarcoma and that the overexpression was associated with an unfavorable prognosis and tumor node metastasis staging. The knockdown of CPXM2 in cultured osteosarcoma cells significantly impeded cell proliferation and migration. In addition, the upregulation of CPXM2 in fetal osteoblast cells significantly promoted cell proliferation and migration. Besides, western blotting results revealed that several key molecules involved in the epithelial mesenchymal transition (EMT) were regulated by CPXM2. CONCLUSION: Taken together, these results imply an active role for CPXM2 in promoting tumor aggressiveness via epithelial to mesenchymal transition (EMT) modulation in osteosarcoma.

[Ultrasound-guided suprascapular nerve block combined with acupuncture for the treatment of calcified tendinitis of rotator cuff].

OBJECTIVE: To explore the method and effect of ultrasound-guided suprascapular nerve block combined with acupuncture in the treatment of calcified tendinitis of rotator cuff. METHODS: From January 2015 to December 2017, total 30 patients with calcified tendinitis, including 23 cases of supraspinatus tendon, 5 cases of infraspinatus tendon and 2 cases of subscapular tendon, were treated with ultrasound-guided suprascapular nerve block combined with acupuncture. There were 7 males and 23 females, ranging in age from 36 to 71 years old, with an average of 51.6 years old. There were 17 cases on the right and 13 cases on the left. VAS pain score, Constant-murley score, UCLA score and X-ray examination were used to evaluate the clinical results before and after surgery. RESULTS: The mean follow-up was 14.3 months (6 to 30 months). The preoperative VAS score was 3.82±1.13, Constant-Murley score was 36.91±7.95 and UCLA score was 11.35±2.17. The final follow-up scores were 1.32±1.06, 90.61±2.89 and 33.22±1.51, respectively. The final follow-up scores were improved significantly(P<0.05). CONCLUSIONS: Conservative treatment of calcified rotator cuff tendinitis is ineffective. Suprascapular nerve block guided by ultrasound combined with acupuncture has a good therapeutic effect. It is a minimally invasive, economic, safe and effective method, which is worth promoting.