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1.
Mol Biol Rep ; 51(1): 636, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727863

ABSTRACT

BACKGROUND: Osteoporosis (OP), characterized by compromised bone integrity and increased fracture risk, poses a significant health challenge. Circular RNAs (circRNAs) have emerged as crucial regulators in various pathophysiological processes, prompting investigation into their role in osteoporosis. This study aimed to elucidate the involvement of circCOX6A1 in OP progression and understand its underlying molecular mechanisms. The primary objective was to explore the impact of circCOX6A1 on bone marrow-derived mesenchymal stem cells (BMSCs) and its potential interactions with miR-512-3p and DYRK2. METHODS: GSE161361 microarray analysis was employed to assess circCOX6A1 expression in OP patients. We utilized in vitro and in vivo models, including BMSC cultures, osteogenic differentiation assays, and an OVX-induced mouse model of OP. Molecular techniques such as quantitative RT-PCR, western blotting, and functional assays like alizarin red staining (ARS) were employed to evaluate circCOX6A1 effects on BMSC proliferation, apoptosis, and osteogenic differentiation. The interaction between circCOX6A1, miR-512-3p, and DYRK2 was investigated through dual luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down assays. RESULTS: CircCOX6A1 was found to be upregulated in osteoporosis patients, and its expression inversely correlated with osteogenic differentiation of BMSCs. CircCOX6A1 knockdown enhanced osteogenic differentiation, as evidenced by increased mineralized nodule formation and upregulation of osteogenic markers. In vivo, circCOX6A1 knockdown ameliorated osteoporosis progression in OVX mice. Mechanistically, circCOX6A1 acted as a sponge for miR-512-3p, subsequently regulating DYRK2 expression. CONCLUSION: This study provides compelling evidence for the role of circCOX6A1 in osteoporosis pathogenesis. CircCOX6A1 negatively regulates BMSC osteogenic differentiation through the miR-512-3p/DYRK2 axis, suggesting its potential as a therapeutic target for mitigating OP progression.


Subject(s)
Cell Differentiation , Dyrk Kinases , Mesenchymal Stem Cells , MicroRNAs , Osteogenesis , Osteoporosis , Protein Serine-Threonine Kinases , Protein-Tyrosine Kinases , RNA, Circular , Animals , Mice , Apoptosis/genetics , Cell Differentiation/genetics , Cell Proliferation/genetics , Disease Models, Animal , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Osteogenesis/genetics , Osteoporosis/genetics , Osteoporosis/metabolism , Osteoporosis/pathology , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism
2.
J Nanobiotechnology ; 22(1): 314, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840113

ABSTRACT

Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.


Subject(s)
Calcium , Magnesium , Nanoparticles , Osteogenesis , Osteoporosis , Osteogenesis/drug effects , Osteoporosis/drug therapy , Magnesium/pharmacology , Magnesium/chemistry , Calcium/metabolism , Animals , Nanoparticles/chemistry , Mice , Inflammation/drug therapy , Bone and Bones/drug effects , Bone and Bones/metabolism , Humans , Cellular Microenvironment/drug effects , Female , NF-kappa B/metabolism
3.
Med Sci Monit ; 30: e943176, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39026435

ABSTRACT

BACKGROUND Pyogenic spondylodiscitis is infection of the intervertebral disc or discs and the adjacent vertebrae. This retrospective study aimed to compare the effectiveness of percutaneous endoscopic lumbar debridement (PELD) versus posterior lumbar interbody fusion (PLIF) in 40 patients with pyogenic spondylodiscitis (PSD). MATERIAL AND METHODS Medical records of patients who underwent PELD (n=18) or PLIF (n=22) for PSD between 2018 and 2023 were reviewed. The recorded outcomes encompassed surgical duration, intraoperative blood loss, Oswestry Disability Index (ODI) measurements, Visual Analog Scale (VAS) assessments, C-reactive protein (CRP) levels, duration of hospitalization, erythrocyte sedimentation rate (ESR), American Spinal Injury Association (ASIA) grading, lumbar sagittal parameters, and the incidence of complications. RESULTS The PELD group had shorter surgical duration, less intraoperative blood loss, and shorter length of hospital stay compared to the PLIF group (P<0.01). At the last follow-up, both groups had significant improvement in ESR, CRP levels, and ASIA classification (P<0.001), but there was no significant difference between the 2 groups (P>0.05). The PELD group had lower ODI and VAS ratings at 1 month and 3 months, respectively (P<0.01). The PLIF group had significant improvements in intervertebral space height and lumbar lordosis angle (P<0.01). CONCLUSIONS Both PLIF and PELD surgical approaches demonstrate adequate clinical efficacy in the treatment of monosegmental PSD. PLIF can better ensure more spinal stability than PELD, but PELD offers advantages such as reduced minimal surgical trauma, shorter operative duration, and faster recovery after surgery.


Subject(s)
Debridement , Discitis , Lumbar Vertebrae , Minimally Invasive Surgical Procedures , Spinal Fusion , Humans , Male , Female , Discitis/surgery , Middle Aged , Spinal Fusion/methods , Lumbar Vertebrae/surgery , Debridement/methods , Retrospective Studies , Treatment Outcome , Minimally Invasive Surgical Procedures/methods , Aged , Adult , Endoscopy/methods , Length of Stay , Operative Time
4.
BMC Musculoskelet Disord ; 25(1): 568, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033154

ABSTRACT

BACKGROUND: Andersen's lesion (AL) is a rare complication of ankylosing spondylitis (AS), characterized by nonneoplastic bone destruction, typically manifested as bone destruction and sclerosis in the vertebral body and/or intervertebral disc area. At present, there is no consensus on the pathology and etiology of AL. Repeated trauma, inflammation in essence and part of the natural history of Ankylosing spondylitis itself are the most widely recognized theories of the etiology of AL. However, positive bacteria cultured in bone biopsy of Andersen's lesion (AL) in Ankylosing spondylitis patients are extremely rare. Herein, we report a rare case of detecting Ewingella americana from a patient with Andersson lesion in ankylosing spondylitis by Metagenomic Next-Generation Sequencing (mNGS) Test. CASE PRESENTATION: This case involved a 39-year-old male with a history of AS for 11 years, who developed AL (T11/12) in the thoracic vertebrae. After sufficient preoperative preparation, we successfully performed one-stage posterior approach corrective surgery and collected bone biopsies samples for examination. Cultured bacteria were not found, and pathological histology indicated infiltration of inflammatory cells. However, it is worth noting that we discovered a gram-negative bacterium, the Ewingella americana, through mNGS testing. Further histopathological examination suggests chronic inflammatory cell infiltration. After one-stage posterior approach corrective surgery, the patient's condition significantly improved. At the 6-month follow-up, the pain significantly decreased, and the patient returned to normal life. CONCLUSION: We detected Ewinia americana in the bone biopsies of Andersson lesion (AL) in ankylosing spondylitis patient by mNGS.


Subject(s)
High-Throughput Nucleotide Sequencing , Spondylitis, Ankylosing , Humans , Spondylitis, Ankylosing/diagnosis , Spondylitis, Ankylosing/complications , Spondylitis, Ankylosing/microbiology , Male , Adult , Metagenomics , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/microbiology , Thoracic Vertebrae/pathology , Thoracic Vertebrae/surgery
5.
BMC Genomics ; 24(1): 181, 2023 Apr 05.
Article in English | MEDLINE | ID: mdl-37020267

ABSTRACT

BACKGROUND: CircRNAs are involved in the pathogenesis of several central nervous system diseases. However, their functions and mechanisms in spinal cord injury (SCI) are still unclear. Therefore, the purpose of this study was to evaluate circRNA and mRNA expression profiles in the pathological setting of SCI and to predict the potential function of circRNA through bioinformatics. METHODS: A microarray-based approach was used for the simultaneous measurement of circRNAs and mRNAs, together with qPCR, fluorescence in situ hybridization, western immunoblotting, and dual-luciferase reporter assays to investigate the associated regulatory mechanisms in a rat SCI model. RESULTS: SCI was found to be associated with the differential expression of 414 and 5337 circRNAs and mRNAs, respectively. Pathway enrichment analyses were used to predict the primary function of these circRNAs and mRNAs. GSEA analysis showed that differentially expressed mRNAs were primarily associated with inflammatory immune response activity. Further screening of these inflammation-associated genes was used to construct and analyze a competing endogenous RNA network. RNO_CIRCpedia_4214 was knocked down in vitro, resulting in reduced expression of Msr1, while the expression of RNO-miR-667-5p and Arg1 was increased. Dual-luciferase assays demonstrated that RNO_CIRCpedia_4214 bound to RNO-miR-667-5p. The RNO_CIRCpedia_4214/RNO-miR-667-5p/Msr1 axis may be a potential ceRNA that promotes macrophage M2-like polarization in SCI. CONCLUSION: Overall, these results highlighted the critical role that circRNAs may play in the pathophysiology of SCI and the discovery of a potential ceRNA mechanism based on novel circRNAs that regulates macrophage polarization, providing new targets for the treatment of SCI.


Subject(s)
MicroRNAs , Spinal Cord Injuries , Animals , Rats , In Situ Hybridization, Fluorescence , Luciferases/genetics , MicroRNAs/genetics , RNA, Circular/genetics , RNA, Messenger/genetics , Spinal Cord Injuries/genetics , Scavenger Receptors, Class A/metabolism
6.
Cancer Cell Int ; 23(1): 215, 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37752544

ABSTRACT

BACKGROUND: The aim of this study was to determine the underlying potential mechanisms and function of DIO3OS, a lincRNA in osteosarcoma and clarify that DIO3OS can be used as a potential diagnostic biomarker and immunotherapeutic target. METHODS: The expression matrix data and clinical information were obtained from XENA platform of UCSC and GEO database as the test cohorts. The external validation cohort was collected from our hospital. Bioinformatics analysis was used to annotate the biological function of DIO3OS. Immune infiltration and immune checkpoint analysis were applied to evaluate whether DIO3OS can be used as an immunotherapeutic target. ROC curves and AUC were established to assess the diagnostic value of DIO3OS for differentiating patients from other subtypes sarcoma. The expression analysis was detected by qRT-PCR, western blot, and immunohistochemical. Wound healing assay and Transwell assay were applied to determine the migration and invasion function of DIO3OS in osteosarcoma cell lines. The tail vein injection osteosarcoma cells metastases model was used in this research. RESULTS: High expression of DIO3OS was identified as a risk lincRNA for predicting overall survival of osteosarcoma in test cohort. The outcomes of experiments in vitro and in vivo showed that low expression of DIO3OS limited osteosarcoma tumor metastasis with inhibiting TGF-ß signaling pathway. Immune checkpoint genes (CD200 and TNFRSF25) expressions were inhibited in the low DIO3OS expression group. The DIO3OS expression can be applied to reliably distinguish osteosarcoma from lipomatous neoplasms, myomatous neoplasms, nerve sheath tumors, and synovial-like neoplasms. This result was further validated in the validation cohort. CONCLUSIONS: In conclusion, our outcomes indicated that DIO3OS is a potential diagnostic and prognostic biomarker of osteosarcoma, emphasizing its potential as a target of immunotherapy to improve the treatment of osteosarcoma through TGF-ß signaling pathway. TRIAL REGISTRATION NUMBER: The present retrospectively study was approved by the Ethics Committee of The Second Affiliated Hospital of Nanchang University [Review (2020) No. (115)].

7.
Med Sci Monit ; 29: e939844, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37580900

ABSTRACT

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) has gained popularity as a minimally invasive surgery for treating lumbar disc herniation. However, there is limited research focusing on the reoperation rate and its associated factors. This study aims to investigate the rate of reoperation and identify the causes and risk factors for reoperation after PELD. MATERIAL AND METHODS We conducted a retrospective analysis of patients who underwent PELD (interlaminar and transforaminal approaches) at our hospital from November 2016 to May 2020. A matched case-control design was employed to identify relevant risk factors for reoperation, with a matching ratio of 1:3. Clinical characteristics and radiological parameters were compared, and univariate analysis was performed using independent samples t-test and chi-squared test. RESULTS Among the 435 patients included in the study, the reoperation rate for those with a minimum 2-year follow-up was 6.2% (27/435). The causes of reoperation and their respective rates were as follows: recurrence of lumbar disc herniation (3.2%, 14/435), incomplete decompression (1.8%, 8/435), persistent low back pain (0.7%, 3/435), and postoperative infection (0.5%, 2/435). Univariate analysis revealed that age (P=0.015), Pfirrmann grade IV-V (P=0.017), and lack of active straight leg raise exercises (P=0.026) were significantly associated with reoperation. Multiple logistic regression analysis indicated that age (P=0.001), Pfirrmann grade IV-V (P=0.033), and lack of active straight leg raise exercises postoperatively (P=0.003) were independent risk factors for reoperation after PELD. CONCLUSIONS The primary cause of reoperation in lumbar disc herniation patients after PELD was recurrence of the herniation. Additionally, severe disc degeneration, older age, and lack of active straight leg raise exercises were identified as significant risk factors associated with an increased reoperation rate.


Subject(s)
Diskectomy, Percutaneous , Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/surgery , Diskectomy, Percutaneous/methods , Retrospective Studies , Reoperation , Follow-Up Studies , Lumbar Vertebrae/surgery , Diskectomy/adverse effects , Diskectomy/methods , Endoscopy/adverse effects , Endoscopy/methods , Risk Factors , Research Design , Treatment Outcome
8.
Med Sci Monit ; 29: e938577, 2023 Apr 04.
Article in English | MEDLINE | ID: mdl-37012682

ABSTRACT

BACKGROUND Multi-segment herniation of lumbar intervertebral discs is a complex lumbar spine disease, and it is difficult to identify the responsible segment using only magnetic resonance imaging (MRI). The present study screened 47 patients with multi-segment lumbar disc herniation (MSLDH) to evaluate coronal magnetic resonance imaging (CMRI) of three-dimensional fast-field echo with water-selective excitation to identify the responsible segment of multi-segment lumbar disc herniation (MSLDH) and to assess the accuracy and utility of CMRI. MATERIAL AND METHODS This retrospective study included 44 patients with low back pain or lower-extremity symptoms from January 2019 to December 2021. The imaging (including CMRI) and clinical data of the patients were analyzed by 3 independent, blinded experts. The Kappa statistical method was used to characterize the reader-to-reader reliability to qualitatively evaluate the data. RESULTS CMRI showed high diagnostic performance, with 90.2% sensitivity, 94.9% positive predictive value (PPV), 80% negative predictive value (NPV), and 83.4% accuracy, and there were significant differences in hospital length of stay (P=0.013) and surgical bleeding (P=0.006) (P<0.01) between single-segment and multi-segment patients. CONCLUSIONS CMRI is highly accurate in revealing the shape, signal, and position of the intraspinal and extraspinal lumbosacral plexus, and reducing surgical segments can help improve postoperative outcomes for patients.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Intervertebral Disc , Humans , Intervertebral Disc Displacement/surgery , Retrospective Studies , Reproducibility of Results , Magnetic Resonance Imaging/methods , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/pathology , Lumbar Vertebrae/surgery
9.
Med Sci Monit ; 29: e942137, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38124352

ABSTRACT

BACKGROUND Key-hole surgery is a minimally invasive technique that has shown promise in various surgical procedures. This study aimed to assess the clinical effectiveness of preoperative coronal MRI-assisted key-hole surgery for the treatment of patients with cervical spondylotic radiculopathy (CSR). MATERIAL AND METHODS A total of 30 patients diagnosed with CSR and undergoing key-hole surgery with CMRI assistance were included in the study. Various parameters, including surgical segments, incision length, disease duration, operative time, intraoperative fluoroscopy times, intraoperative blood loss, complications, and length of hospitalization, were recorded. Precise measurements of Cobb angles and intervertebral space height were taken before and after the surgical procedure. Surgical outcomes were evaluated using modified Macnab criteria, visual analogue scale (VAS), Japanese Orthopaedic Association Scores (JOA), and neck disability index (NDI). RESULTS The average duration of disease was 6.47±3.29 months, with an average incision length of 1.94±0.15 cm and operative time of 57.83±4.34 minutes. The average intraoperative blood loss was 33.70±9.28 ml, with an average of 3.50±0.73 intraoperative fluoroscopies. The average duration of hospitalization was 4.10±1.27 days. Preoperative and postoperative measurements showed no statistically significant difference in C2-C7 Cobb angles and intervertebral space height. However, there were significant improvements in postoperative VAS, NDI, and JOA scores compared to preoperative scores. The surgical effectiveness rate was 100%, with a high rate of good and excellent outcomes. CONCLUSIONS The findings of this study suggest that preoperative CMRI-assisted key-hole surgery for single-segment CSR is a safe and effective treatment option with low complication rates. The clinical benefits include high security and good outcomes. Further research and larger studies are warranted to validate these findings.


Subject(s)
Radiculopathy , Spinal Fusion , Spondylosis , Humans , Radiculopathy/diagnostic imaging , Radiculopathy/surgery , Blood Loss, Surgical , Spondylosis/diagnostic imaging , Spondylosis/surgery , Spondylosis/complications , Minimally Invasive Surgical Procedures/adverse effects , Treatment Outcome , Spinal Fusion/methods , Magnetic Resonance Imaging , Retrospective Studies , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery
10.
Lipids Health Dis ; 22(1): 204, 2023 Nov 25.
Article in English | MEDLINE | ID: mdl-38007425

ABSTRACT

BACKGROUND: Intervertebral disc degeneration (IVDD) is widely recognized as the primary etiological factor underlying low back pain, often necessitating surgical intervention as the sole recourse in severe cases. The metabolic pathway of arachidonic acid (AA), a pivotal regulator of inflammatory responses, influences the development and progression of IVDD. METHODS: Initially, a comparative analysis was conducted to investigate the relationship between AA expression patterns and different stages of IVDD using single-cell sequencing (scRNA-seq) data. Additionally, three machine learning methods (LASSO, random forest, and support vector machine recursive feature elimination) were employed to identify hub genes associated with IVDD. Subsequently, a novel artificial intelligence prediction model was developed for IVDD based on an artificial neural network algorithm and validated using an independent dataset. The identified hub genes were further subjected to functional enrichment, immune infiltration, and Connectivity Map analysis. Moreover, external validation was performed using flow cytometry and real-time reverse transcription polymerase chain reaction analysis. RESULTS: Both scRNA-seq and bulk RNA-seq data revealed a positive correlation between the severity of IVDD and the AA metabolic pathway. They also revealed increased AA metabolic activity in macrophages and neutrophils, as well as enhanced intercellular communication with nucleus pulposus cells. Utilizing advanced machine learning algorithms, five hub genes (AKR1C3, ALOX5, CYP2B6, EPHX2, and PLB1) were identified, and an incipient diagnostic model was developed with an AUC of 0.961 in the training cohort and 0.72 in the validation cohort. An in-depth exploration of the functionality of these hub genes revealed their notable association with inflammatory responses and immune cell infiltration. Lastly, AH6809 was found to delay IVDD by inhibiting AKR1C3. CONCLUSIONS: This study offers comprehensive insights into potential biomarkers and small molecules associated with the early pathogenesis of IVDD. The identified biomarkers and the developed integrated diagnostic model hold great promise in predicting the onset of early IVDD. AH6809 was established as a therapeutic target for AKR1C3 in the treatment of IVDD, as evidenced by computer simulations and biological experiments.


Subject(s)
Artificial Intelligence , Intervertebral Disc Degeneration , Humans , Arachidonic Acid , Intervertebral Disc Degeneration/genetics , Multiomics , Biomarkers
11.
Childs Nerv Syst ; 39(1): 275-278, 2023 01.
Article in English | MEDLINE | ID: mdl-35798908

ABSTRACT

BACKGROUND: Posterior ring apophysis fracture (PRAF), accompanied with lumbar disc herniation (LDH), is a rare occurrence. Owing to its rarity, there is no consensus on the treatment strategy for this condition. Differences mainly encompass the type of decompression method, the need for additional spinal fusion, the need for apophysis fragments or/and disc materials removal, and long-term efficacy, particularly, compared to LDH alone. Hence, the aim of this study was to describe a rare instance of PRAF with LDH in a 12-year-old professional diver, who was successfully treated with percutaneous endoscopic interlaminar discectomy (PEID), and to initiate a discussion involving several meaningful and related factors.


Subject(s)
Diskectomy, Percutaneous , Intervertebral Disc Displacement , Humans , Child , Intervertebral Disc Displacement/surgery , Lumbar Vertebrae/surgery , Retrospective Studies , Endoscopy/methods , Diskectomy, Percutaneous/methods , Diskectomy , Treatment Outcome
12.
Cancer Cell Int ; 22(1): 322, 2022 Oct 16.
Article in English | MEDLINE | ID: mdl-36244998

ABSTRACT

Osteosarcoma is a highly malignant tumor, with very high disability and fatality rates. However, the overall prognosis is not optimistic. Pyroptosis is a newly discovered cell death modality accompanied by inflammation, which is closely related to varieties of cancers. In this study, the RNA-seq data were downloaded from public databases, the differences in the expression of the pyroptosis-related genes (PRGs) were identified, and the six PRGs signature was established through the univariate and LASSO Cox analysis. The patients were grouped according to the PRGs signature, and the prognosis between the two groups was further compared. In addition, a ten pyroptosis-related lncRNAs (PRLs) prognostic signature was also constructed. Through functional analysis of the differentially expressed genes (DEGs), the immune-related pathways were found to be enriched. The Pearson correlation analysis showed a strong correlation between the pyroptosis-related biomarkers. Finally, we identified a promising biomarker, CHMP4C, which is highly expressed in osteosarcoma. Overexpression of CHMP4C promoted the proliferation, migration and invasion of the osteosarcoma cell. Our results thus provide new evidence for exploring prognostic biomarkers and therapeutic targets of osteosarcoma.

13.
J Musculoskelet Neuronal Interact ; 21(1): 130-137, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33657763

ABSTRACT

OBJECTIVES: Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown. METHODS: To investigate the function of immune cells in osteosarcoma, we provided a text-based GMT (Gene Matrix Transposed) file in which each line defines one of lm22 with their markers. We used STRING to draw DEG's PPI network and selected hub genes and modules. Then, survival analysis was conducted to hub genes. We identified 10,390 common genes, and identified 218 DEGs based on the combined t-value and Z scores. RESULTS: The KEGG and GSEA enrichment analysis showed that macrophages are significantly activated in osteosarcoma. PPI network analysis revealed that hub gene CD163 molecule. We found that the expression of CD163 was negatively associated with the OS of osteosarcoma patients. These results suggest that macrophages are a risk factor in patients with osteosarcoma. CONCLUSIONS: This study has systematically validated results of the studies carried out previously and filled up the gap in the field of OS on large-scaled meta-analysis. In addition, for the hub gene (CD163) and the macrophage cell capable of being used as a novel biomarker in promoting early diagnosis and development of therapeutic approaches.


Subject(s)
Bone Neoplasms/immunology , Databases, Genetic , Immunity, Cellular/physiology , Macrophages/immunology , Osteosarcoma/immunology , Tumor Microenvironment/physiology , Antigens, CD/genetics , Antigens, Differentiation, Myelomonocytic/genetics , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Gene Regulatory Networks/genetics , Humans , Macrophages/pathology , Osteosarcoma/genetics , Osteosarcoma/pathology , Prognosis , Protein Array Analysis/methods , Receptors, Cell Surface/genetics
14.
J Cell Biochem ; 120(10): 17167-17179, 2019 10.
Article in English | MEDLINE | ID: mdl-31111559

ABSTRACT

Proinflammatory cytokine such as interleukin (IL)-1ß causes inflammation of articular cartilage. In this current study, we explored the chondroprotective effects of long noncoding RNA (lncRNA) MALAT-1 on cell proliferation, apoptosis, and matrix metabolism in IL-1ß-induced inflammation in articular chondrocytes. Articular chondrocytes from knee joints of normal rats were isolated and cultured, followed by identification through observation of toluidine blue and COL II immunocytochemical stainings. The proliferation of chondrocytes at passage 2 was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The inflammatory chondrocytes induced by 10 ng/mL IL-1ß were observed and identified by toluidine blue and COL II immunocytochemical stainings. pcDNA 3.1 and pcDNA-MALAT-1 were transfected in the chondrocytes. Ultrastructure of chondrocytes was observed by using a transmission electron microscope. The MTT assay was carried out to evaluate chondrocyte viability. Hoechst 33258 staining and flow cytometry were adopted to assess chondrocyte apoptosis. The chondrocytes at passage 2 with the biological characteristics of chondrocytes were used for subsequent experiments. In IL-1ß-treated chondrocytes, the growth rate of chondrocytes slowed down, the cells became narrow and long, the vacuoles were seen in the cells, and the morphology of the chondrocytes was irregular. The toluidine blue staining and the immunohistochemical staining of COL II became weaker. In response to IL-1ß induction, articular chondrocytes showed reduced MALAT-1 expression; moreover, obvious cartilage injury was observed with decreased chondrocyte viability and Col II expression and elevated chondrocyte apoptosis, MMP-13 expression, and p-JNK expression. With the treatment of pcDNA-MALAT-1, the cartilage injury was alleviated with increased chondrocyte viability and type II collagen (Col II) expression and reduced chondrocyte apoptosis, MMP-13 expression and p-JNK expression. Taken together these results, lncRNA MALAT-1 blocked the activation of the JNK signaling pathway; thereby, IL-1ß-induced inflammation in articular chondrocytes was reduced with enhanced chondrocyte proliferation and suppressed chondrocyte apoptosis and extracellular matrix degradation.


Subject(s)
Chondrocytes/drug effects , Interleukin-1beta/pharmacology , MAP Kinase Kinase 4/genetics , MAP Kinase Signaling System/genetics , RNA, Long Noncoding/genetics , Animals , Animals, Newborn , Apoptosis/drug effects , Apoptosis/genetics , Cartilage, Articular/cytology , Cartilage, Articular/metabolism , Cell Proliferation/drug effects , Chondrocytes/metabolism , Chondrocytes/pathology , Collagen Type II/genetics , Collagen Type II/metabolism , Gene Expression Regulation , Inflammation , MAP Kinase Kinase 4/metabolism , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Models, Biological , Plasmids/chemistry , Plasmids/metabolism , Primary Cell Culture , RNA, Long Noncoding/agonists , RNA, Long Noncoding/metabolism , Rats , Transfection
15.
Biochem Biophys Res Commun ; 503(2): 791-797, 2018 09 05.
Article in English | MEDLINE | ID: mdl-29928874

ABSTRACT

Serum deprivation is a likely contributor to intervertebral disc (IVD) degeneration (IVDD).17ß-estradiol (E2) have been noted to protect nucleus pulposus cells (NPCs) against apoptosis. Autophagy and apoptosis play a paramount role in maintaining the homeostasis of IVD. So far, little research has been published on whether autophagy plays a role for the E2 mediated protection of NPCs. The aim of this study is to understand whether autophagy is involved in the protective effect of E2 against serum deprivation-induced cell apoptosis and expression of matrix metalloproteinase (MMP)-3 and MMP-13. mCherry-GFP-LC3-adenovirus transfection is used to monitor autophagy detection. The expression levels of autophagy-related proteins were measured by Western blotting, Apoptosis and MMPs were detected by flow cytometry and Western blotting. Accordingly, Autophagy and apoptosis was detected in NP cells under serum deprivation conditions, the autophagy incidence began to reached a peak value at 48 h, the apoptosis and MMPs incidence began reached a minimum value treat with E2 (10-7 M). Whereas the combined use of E2 and 3-MA led to a dramatic decrease in autophagy, while aberrantly elevated expression levels of apoptotic and MMPs. These data suggest that serum deprivation-induced apoptosis and MMP-3, MMP-13, which was efficiently suppressed by the E2 through promoting autophagy in rat NPCs.


Subject(s)
Apoptosis , Estradiol/metabolism , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 3/metabolism , Nucleus Pulposus/cytology , Animals , Autophagy , Cells, Cultured , Cytoprotection , Nucleus Pulposus/metabolism , Rats , Rats, Sprague-Dawley , Serum/metabolism
16.
BMC Musculoskelet Disord ; 19(1): 154, 2018 May 22.
Article in English | MEDLINE | ID: mdl-29788940

ABSTRACT

BACKGROUND: Since disc sequestration that mimics a tumor is rare and sometimes presents with an atypical appearance upon magnetic resonance imaging (MRI), it is often confused with other more common epidural and intradural neoplasms, particularly neurinoma. Open surgery is necessary due to the difficult of achieving a definitive diagnosis using computed tomography, MRI, and gadolinium- enhanced MRI prior to operation. Herein, we describe the use of coronal MR images of 3D fast-field echo with water selective excitation in the diagnosis of disc sequestration mimicking a tumor. CASE PRESENTATION: Two patients were admitted to our hospital with back pain, radiating pain, and hypoesthesia in the right lower limb. MRI revealed tumor-like masses in the lateral recess of L3 and posterior to the body of L4. The initial diagnosis indicated disc sequestration mimicking a tumor and neurinoma. The coronal MR images of 3D fast-field echo with water selective excitation showed a clear boundary between the tumor-like mass and the nerve root. Moreover, the mass was also completely separated from the dura. Therefore, neurinoma was excluded as a possible diagnosis prior to operation. Surgical excision to perform removal of the gross mass was performed in one patient. The histopathological diagnosis was consistent with the 3D fast-field echo with water-selective excitation MRI. Another patient was successfully treated by minimally invasive endoscopic surgery. CONCLUSIONS: Disc sequestration that mimics a tumor is difficult to diagnose preoperatively. As a non-invasive strategy, coronal MR images of 3D fast-field echo with water selective excitation is a helpful imaging tool for differentiating between diagnosis of disc sequestration that mimics a tumor and neurinoma prior to operation. If the disc fragment of mimicking tumor can be identified prior to operation, open surgery may not be necessary for all patients. Minimally invasive endoscopic surgery also is an alternative strategy.


Subject(s)
Imaging, Three-Dimensional/methods , Intervertebral Disc/diagnostic imaging , Magnetic Resonance Imaging/methods , Neurilemmoma/diagnostic imaging , Spinal Neoplasms/diagnostic imaging , Diagnosis, Differential , Humans , Imaging, Three-Dimensional/standards , Intervertebral Disc/surgery , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/surgery , Magnetic Resonance Imaging/standards , Male , Middle Aged , Neurilemmoma/surgery , Spinal Neoplasms/surgery
17.
Med Sci Monit ; 23: 4855-4864, 2017 Oct 10.
Article in English | MEDLINE | ID: mdl-29016554

ABSTRACT

BACKGROUND This study aimed to evaluate the validity of modified laminoplasty in treating close-base OPLL with an occupying ratio of more than 60%. MATERIAL AND METHODS Forty-seven close-base OPLL patients with an occupying ratio of more than 60% were treated through modified laminoplasty (N=22) and combined anterior-posterior approach (N=25) in the study, including 17 females and 30 males, with a mean age of 60.59±6.76 years (ranging from 46 to 75 years). The patients' characteristics, the recovery rate of neurological function, length of the operation, intraoperative blood loss, hospital costs, and complications were recorded and compared between the 2 groups. RESULTS The recovery rate of neurological function did not demonstrate a significant difference between the 2 groups (P=0.886). However, length of the operation and intraoperative blood loss in the modified laminoplasty group were shorter than those in the combined anterior-posterior approach group (P=0.001 and P=0.023). Moreover, the mean hospital costs in the modified laminoplasty group (5166.61±123.27 USD) decreased by 33.6% compared with the combined anterior-posterior approach group (7780.12±256.73 USD). Additionally, the complications of the modified laminoplasty group were lower than in the combined anterior-posterior approach group. CONCLUSIONS Modified laminoplasty may be considered a safe and effective strategy for patients that have demonstrated close-base OPLL with an occupying ratio of more than 60% and who cannot endure the trauma caused by the combined anterior-posterior approach due to medical disease.


Subject(s)
Laminoplasty/adverse effects , Laminoplasty/methods , Ossification of Posterior Longitudinal Ligament/surgery , Uterine Cervical Neoplasms/surgery , Aged , Cervical Vertebrae/surgery , Female , Follow-Up Studies , Humans , Laminectomy/adverse effects , Longitudinal Ligaments/physiology , Male , Middle Aged , Osteogenesis/physiology , Retrospective Studies , Spinal Cord Diseases/surgery , Spinal Fusion/methods , Treatment Outcome , Uterine Cervical Neoplasms/therapy
18.
Am J Ther ; 23(6): e1602-e1611, 2016.
Article in English | MEDLINE | ID: mdl-26164021

ABSTRACT

Our study assessed the effect of bone marrow mesenchymal stem cells (BMSCs) expressing inducible hepatocyte growth factor (HGF) on the recovery of femoral head necrosis (FHN). BMSCs were isolated by density gradient centrifugation. A recombinant AdTRE-HGF was constructed as the response plasmid and Adeno-X Tet-on as the regulator vector. The regulator and the response vectors were coinfected into BMSCs and induced at 0, 200, 500, 1000, and 1200 ng/mL doxycycline (Dox). After 3 days, the concentration of HGF was determined using enzyme-linked immunosorbent assay. Forty rabbits were selected to establish the FHN model and divided into 4 experimental groups. After the rabbits were killed by ketamine overdose, the restoration of FHN was assessed. The distribution of HGF-positive cells was observed by immunohistochemical method. Enzyme-linked immunosorbent assay results showed that 1000 ng/mL Dox induced the highest HGF expression level, even higher than the 1200 ng/mL Dox induction. The highest osteonecrosis incidence and empty lacunae percentage were found in group A compared with all the other groups (all P < 0.05). Furthermore, dramatically lower osteonecrosis incidence and empty lacunae percentage were found in group C compared with those of groups B and D (all P < 0.05). A significantly higher level of HGF protein was detected in group C compared with the other groups (all P < 0.05). Our study successfully developed the AdTRE-HGF, a recombinant adenovirus carrying HGF gene, for high expression of HGF in BMSCs. Importantly, introduction of BMSCs expressing HGF successfully produced the desired therapeutic effect in reversing FHN, in a Dox-dependent manner.


Subject(s)
Doxycycline/pharmacology , Femur Head Necrosis/therapy , Hepatocyte Growth Factor/biosynthesis , Hepatocyte Growth Factor/therapeutic use , Mesenchymal Stem Cells/metabolism , Animals , Dose-Response Relationship, Drug , Doxycycline/administration & dosage , Enzyme-Linked Immunosorbent Assay , Genetic Vectors , Hepatocyte Growth Factor/administration & dosage , Male , Rabbits
19.
Eur Spine J ; 24 Suppl 4: S619-22, 2015 May.
Article in English | MEDLINE | ID: mdl-25805579

ABSTRACT

INTRODUCTION: Nontraumatic posterior atlantooccipital dislocation has only been rarely reported. In the current study, the authors reported an extremely rare case of nontraumatic posterior atlantooccipital dislocation associated with atlantoaxial instability. MATERIALS AND METHODS: A 47-year-old female was referred with a history of neck pain for 5 years. The patient had no history of trauma. The axial rotation of range of motion of the cervical spine was severely restricted. Posterior atlantooccipital dislocation with atlantoaxial instability was confirmed through conventional radiography, computed tomography and magnetic resonance imaging. We performed realignment of the dislocation and posterior occipitocervical (C0-C2) fusion. After the surgery, the patient's symptoms improved significantly and she manifested neurological improvement. CONCLUSION: To our knowledge, this lesion has not been reported previously. Anomalies of upper cervical spine may have induced this instability.


Subject(s)
Atlanto-Axial Joint/surgery , Atlanto-Occipital Joint/surgery , Joint Dislocations/etiology , Joint Instability/complications , Cervical Vertebrae/surgery , Female , Humans , Joint Dislocations/diagnosis , Joint Dislocations/surgery , Joint Instability/diagnosis , Joint Instability/surgery , Magnetic Resonance Imaging , Middle Aged , Range of Motion, Articular , Spinal Fusion/methods , Tomography, X-Ray Computed
20.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 43(6): 711-6, 2014 11.
Article in Zh | MEDLINE | ID: mdl-25644572

ABSTRACT

The fast development of minimally invasive spine surgery in recent years is based on the advance of endoscopic microsurgery techniques, computer science and medical imaging, as well as the growing concerning of medical humanities. The concept of minimally invasive and precise targeting therapy has been penetrating into various areas of surgery, and minimal tissue damage and fewer complications are the new directions of minimally invasive spine surgery. In this article we review some advances in precise spinal surgery including percutaneous lumbar discectomy, microendoscopic discectomy, computer-assisted orthopedic surgery and robot surgery.


Subject(s)
Lumbar Vertebrae/surgery , Minimally Invasive Surgical Procedures , Endoscopy , Humans , Microsurgery , Robotic Surgical Procedures
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