Differential proteomic analysis of fetal and geriatric lumbar nucleus pulposus: immunoinflammation and age-related intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a major cause of low back pain. Although the mechanism of degeneration remains unclear, aging has been recognized as a key risk factor for IVDD. Most studies seeking to identify IVDD-associated molecular alterations in the context of human age-related IVDD have focused only on a limited number of proteins. Differential proteomic analysis is an ideal method for comprehensively screening altered protein profiles and identifying the potential pathways related to pathological processes such as disc degeneration. METHODS: In this study, tandem mass tag (TMT) labeling was combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for differential proteomic analysis of human fetal and geriatric lumbar disc nucleus pulposus (NP) tissue. Parallel reaction monitoring (PRM) and Western blotting (WB) techniques were used to identify target proteins. Bioinformatic analyses, including Gene Ontology (GO) annotation, domain annotation, pathway annotation, subcellular localization and functional enrichment analyses, were used to interpret the potential significance of the protein alterations in the mechanism of IVDD. Student's t-tests and two-tailed Fisher's exact tests were used for statistical analysis. RESULTS: Six hundred forty five proteins were significantly upregulated and 748 proteins were downregulated in the geriatric group compared with the fetal group. Twelve proteins were verified to have significant differences in abundance between geriatric and fetal NP tissue; most of these have not been previously identified as being associated with human IVDD. The potential significance of the differentially expressed proteins in age-related IVDD was analyzed from multiple perspectives, especially with regard to the association of the immunoinflammatory response with IVDD. CONCLUSIONS: Differential proteomic analysis was used as a comprehensive strategy for elucidating the protein alterations associated with age-related IVDD. The findings of this study will aid in the screening of new biomarkers and molecular targets for the diagnosis and therapy of IVDD. The results may also significantly enhance our understanding of the pathophysiological process and mechanism of age-related IVDD.

Identification of CD8+ T cell-related biomarkers and immune infiltration characteristic of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease, which do not respond well to current treatment partially. Therefore, further in-depth elucidation of the molecular mechanism and pathogenesis of RA is urgently needed for the diagnosis, personalized therapy and drug development. Herein, we collected 111 RA samples from Gene Expression Omnibus (GEO) database, and conducted differentially expressed genes and GESA analysis. Abnormal activation and imbalance of immune cells in RA were observed. WGCNA was utilized to explore the gene modules and CD8+ T cell-related genes (CRGs) were chosen for KEGG and GO analysis. Besides, to explore biomarkers of RA in depth, machine learning algorithms and bioinformatics analysis were used, and we identified GDF15, IGLC1, and IGHM as diagnostic markers of RA, which was confirmed by clinical samples. Next, ssGSEA algorithms were adopted to investigate the differences in immune infiltration of 23 immune cell subsets between RA and healthy control group. Finally, optimal classification analysis based on consensus clustering combined with ssGSEA algorithms were conducted. GDF15 was revealed that to be positively correlated with mast cells and type 2 T helper cells, but negatively correlated with most other immune cells. On the other hand, IGHM and IGLC1 were negatively correlated with CD56dim natural killer cells, while positively associated with other immune cells. Finally, RA samples in subtype A exhibited a higher immune infiltration status. This study could provide guidance for individualized treatment of RA patients and provide new targets for drug design.

Repair of the Injured Spinal Cord by Schwann Cell Transplantation.

Spinal cord injury (SCI) can result in sensorimotor impairments or disability. Studies of the cellular response to SCI have increased our understanding of nerve regenerative failure following spinal cord trauma. Biological, engineering and rehabilitation strategies for repairing the injured spinal cord have shown impressive results in SCI models of both rodents and non-human primates. Cell transplantation, in particular, is becoming a highly promising approach due to the cells' capacity to provide multiple benefits at the molecular, cellular, and circuit levels. While various cell types have been investigated, we focus on the use of Schwann cells (SCs) to promote SCI repair in this review. Transplantation of SCs promotes functional recovery in animal models and is safe for use in humans with subacute SCI. The rationales for the therapeutic use of SCs for SCI include enhancement of axon regeneration, remyelination of newborn or sparing axons, regulation of the inflammatory response, and maintenance of the survival of damaged tissue. However, little is known about the molecular mechanisms by which transplanted SCs exert a reparative effect on SCI. Moreover, SC-based therapeutic strategies face considerable challenges in preclinical studies. These issues must be clarified to make SC transplantation a feasible clinical option. In this review, we summarize the recent advances in SC transplantation for SCI, and highlight proposed mechanisms and challenges of SC-mediated therapy. The sparse information available on SC clinical application in patients with SCI is also discussed.

Clinical Comparison of Selective versus Nonselective Decompression for Symptomatic Tandem Stenosis of the Cervical and Thoracic Spine: A Retrospective Cohort Study.

OBJECTIVE: The aim of the present paper was to reveal the clinical differences between selective and nonselective decompression for symptomatic tandem stenosis of the cervical and thoracic spine (TSCTS). METHODS: A total of 34 patients were eligible and included in the study. Among them, 8 patients underwent selective cervical decompression (CD), 15 patients underwent selective thoracic decompression (TD), and 11 patients underwent combined CD and TD (CTD) surgery. Age, sex, operative time, intraoperative blood loss, postoperative hospital stay, inpatient expenditure, preoperative upper Japanese Orthopaedic Association (JOA) rate, canal occupation rate, high-intensity T2-weighted image (T2WI) of the spinal cord, and preoperative and postoperative JOA scores were compared among the three groups. RESULTS: The CD group had shorter operative time (138.8 ± 36.1 vs 229.7 ± 95.8 vs 328.6 ± 94.8, min, P < 0.001), less intraoperative blood loss (141.3 ± 116.7 vs 496.7 ± 361.8 vs 654.6 ± 320.5, mL, P = 0.004), and shorter postoperative hospital stay (4.6 ± 1.6 vs 9.0 ± 3.5 vs 10.3 ± 6.6, days, P = 0.008), as well as lower preoperative upper JOA rate (34.1 ± 5.6 vs 53.9 ± 8.4 vs 48.2 ± 15.2, %, P = 0.001) than the TD and CTD groups. The CTD group had higher inpatient expenditure than the CD and TD groups (87,850 ± 18,379 vs 55,100 ± 12,890 vs 55,772 ± 15,715, CNY, P < 0.001). The cervical canal occupation rates were similar among different groups (P > 0.05); however, the TD group showed a higher thoracic canal occupation rate than the CD group (58.3 ± 14.7 vs 43.3 ± 12.3, %, P = 0.035). All positive levels in high-intensity T2WI of the spinal cord were decompressed. The preoperative JOA scores as well as the postoperative JOA scores at 6 months and at last follow-up were comparable among the three groups (P > 0.05). Similarly, the JOA recovery rate showed no significant difference among the groups (P > 0.05). CONCLUSION: Selective CD or TD alone demonstrated similar clinical effectiveness to nonselective and combined CTD for TSCTS. Individualized surgical decision should be made after meticulous assessments of clinical and radiological manifestations, general patient condition, and socioeconomic factors.

The Clinical Effect of Manual Reduction Combined with Internal Fixation Through Wiltse Paraspinal Approach in the Treatment of Thoracolumbar Fracture.

OBJECTIVE: To evaluate the clinical outcome of manual reduction combined with pedicle fixation through Wiltse paraspinal approach (WPA) in the treatment of thoracolumbar fractures. METHODS: From May 2017 to May 2019, 48 thoracolumbar fractures patients without neurological symptoms were enrolled in this study. Forty-eight patients were randomly divided into two groups based on the different surgical treatment. Group 1 was manual reduction combined with pedicle screw fixation through Wiltse paraspinal approach treatment group. Group 2 was pedicle screw fixation through traditional posterior approach treatment group. The operation time (OT), intraoperative blood loss (BL), postoperative drainage (PD), time of brace (TB) and the cobb angle recovery of the injured kyphosis in the prone position were obtained and compared between the two groups, respectively. Comparison of cobb angle changes, serum creatine kinase (CK) level, pain visual analogue score (VAS), Oswestry disability index (ODI), and multifidus cross-sectional (MCS) area changes were achieved between the two groups, respectively. RESULTS: Forty-eight patients were enrolled in this study and each group had 24 patients. There was no significant difference between the two groups in patient's age, height, weight, and body mass index (BMI). There were 20 males and four females in group 1. The mean age, height, weight, and BMI of patients were 61.99 ± 11.00 years (range, 42-75 years), 175.21 ± 4.49 cm, 76.71 ± 4.87 kg, and 24.98 ± 1.03 kg/m2 in group 1, respectively. Group 2 had 18 males and six females, and the mean age, height, weight, and BMI of patients were 57.95 ± 9.22 years (range, 44-77 years), 176.37 ± 4.56 cm, 77.42 ± 4.61 kg, and 24.87 ± 1.10 kg/m2 in group 2, respectively. The mean bleeding volume of group 1 was significantly less than group 2 (64.13 ± 9.77 ml and 152.13 ± 10.73 ml, respectively) (P < 0.05). The mean operation time, postoperative drainage, and time of brace were 62.95 ± 9.80 min, 66.25 ± 12.75 ml, and 3.62 ± 0.97 days in group 1, respectively, and they were significantly better than those of group 2 (69.29 ± 6.82min, 162.96 ± 14.55ml and 7.88 ± 1.94 days, respectively) (P < 0.05). The mean multifidus cross-sectional area was significantly smaller than per-operation after surgery in two groups (P < 0.05). The mean creatine kinase of group 1 was 403.13 ± 39.78 U/L and 292.12 ± 45.81 U/L at 1 and 3 days after surgery, respectively, which was significantly smaller than those in group 2 (654.25 ± 53.13 U/L and 467.67 ± 44.25 U/L, respectively) (P < 0.05). The Oswestry disability index of group 1 were significantly better than those in group 2 especially at 1 month and final follow-up after surgery (P < 0.05). Moreover, group 1 also had better outcomes in postoperative Cobb angle change than those in group 2, with significant difference on intra-operation, 1 day and 1 month post-operation (P < 0.05). CONCLUSION: In short, this operation is suitable for thoracolumbar fractures without neurologic symptoms. Preoperative manual reduction had advantages of restoring the height of injured vertebrae. Wiltse intermuscular approach can reduce intraoperative blood loss, shorten operation time, and reduce paraspinal muscle damage. Using the traditional posterior approach, it is easy for surgeons to grasp this technique and it should be recommended as conforming with the minimally invasive approach of recent years.

THAP9-AS1 Promotes Tumorigenesis and Reduces ROS Generation through the JAK2/STAT3 Signaling Pathway by Increasing SOCS3 Promoter Methylation in Osteosarcoma.

Increasing studies have demonstrated that dysfunction of long noncoding RNAs (lncRNAs) plays critical roles in the development of human cancers. THAP9-AS1 has been reported to be dysregulated and associated with tumor progression in some cancers. However, the function and mechanism of THAP9-AS1 in osteosarcoma (OS) remain unclear. In the present study, we found that the expression of THAP9-AS1 was significantly upregulated in OS tissues and associated with the advanced stage of tumors and poor prognosis of patients. Blast comparison results showed that the SOCS3 promoter region and THAP9-AS1 had base complementary pairing binding sites. The interactions between THAP9-AS1, DNA methyltransferases (DNMTs), and SOCS3 were assessed by RIP and ChIP assays. The results of methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) validated that THAP9-AS1 enhanced the methylation level of the SOCS3 promoter. The mRNA levels of SOCS3 in OS cells could be reversed by the demethylation agent 5-aza-2'-deoxycytidine. The mRNA expression of SOCS3 was downregulated in OS tissues and negatively correlated with THAP9-AS1 expression in tumors. Moreover, the western blot and immunofluorescence (IF) assay data showed that THAP9-AS1 activated the JAK2/STAT3 signaling pathway by upregulating p-JAK2 and p-STAT3 and the nuclear translocation of p-STAT3. Functionally, ectopic expression of THAP9-AS1 promoted cell proliferation, migration, and invasion and inhibited apoptosis, and this phenomenon could be reversed by SOCS3. Introduction of the JAK/STAT inhibitor AG490 partially abolished the stimulative effect of THAP9-AS1 on cellular processes. In addition, THAP9-AS1 decreased oxidative stress by reducing reactive oxygen species (ROS) and enhancing the mitochondrial membrane potential of OS cells via the SOCS3/JAK2/STAT3 pathway. Stable overexpression of THAP9-AS1 contributed to tumor growth and metastasis in vivo. In total, our findings suggested that upregulation of THAP9-AS1 might recruit DNMTs to epigenetically inhibit SOCS3, thereby activating the JAK2/STAT3 signaling pathway and oncogenesis of OS. These results provide novel insights for the understanding of OS progression.