Characterization of the gut microbiota and fecal metabolome in the osteosarcoma mouse model.

Previous studies have reported the correlation between gut microbiota (GM), GM-derived metabolites, and various intestinal and extra-intestinal cancers. However, limited studies have investigated the correlation between GM, GM-derived metabolites, and osteosarcoma (OS). This study successfully established a female BALB/c nude mouse model of OS. Mice (n = 14) were divided into the following two groups (n = 7/group): OS group named OG, injected with Saos-2 OS cells; normal control group named NCG, injected with Matrigel. The GM composition and metabolites were characterized using 16S rDNA sequencing and untargeted metabolomics, respectively. Bioinformatics analysis revealed that amino acid metabolism was dysregulated in OS. The abundances of bone metabolism-related genera Alloprevotella, Rikenellaceae_RC9_gut_group, and Muribaculum were correlated with amino acid metabolism, especially histidine metabolism. These findings suggest the correlation between GM, GM-derived metabolites, and OS pathogenesis. Clinical significance: The currently used standard therapeutic strategies for OS, including surgery, chemotherapy, and radiation, are not efficacious. The findings of this study provided novel insights for developing therapeutic, diagnostic, and prognostic strategies for OS.

MiR-134-5p inhibits the malignant phenotypes of osteosarcoma via ITGB1/MMP2/PI3K/Akt pathway.

Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.

Clinical Efficacy of Unilateral Dual-channel Endoscopic Lumbar Interbody Fusion for Lumbar Spondylolisthesis with Spinal Scoliosis.

OBJECTIVES: Scoliosis associated with spondylolisthesis is a common phenomenon. Recent research has reported that scoliosis can spontaneously disappear after lumbar spinal fusion surgery. Researchers have advocated that, for scoliosis associated with vertebral slippage, surgery for the latter may be the only necessary intervention, while unnecessary surgery for scoliosis should be avoided. So we propose that minimally invasive techniques can achieve treatment effects similar to those of open surgery. Therefore, in this study, we aimed to investigate the clinical efficacy of unilateral dual-channel endoscopic lumbar interbody fusion (ULIF) for treating lumbar spondylolisthesis with spinal scoliosis. METHODS: This study retrospectively analyzed patients with lumbar spondylolisthesis and spinal scoliosis who underwent ULIF between September 2021 and September 2023. Measurements of the Cobb angle, lumbar lordosis (LL) angle, sacral slope (SS), slip percentage (SP), slip angle (SA), L1 plumb line-S1 distance (LASD), and average intervertebral height (AIH) were taken preoperatively, immediately following surgery, 3 months after surgery, and at the final follow-up. The visual analogue scale (VAS), Oswestry disability index (ODI), and Japanese Orthopaedic Association (JOA) scoring systems were used to assess clinical results. The surgical efficacy was evaluated by comparing these parameters before and after surgery. Comparison of indicators within the same group was conducted using one-way repeated-measures analysis of variance or paired sample t-tests, whereas between-group differences were compared using an independent t-test. RESULTS: This study included 31 individuals who underwent surgery and completed follow-up. The follow-up period did not show a significant loss of corrective angles. Furthermore, the Cobb angle, SP, SA, and LASD significantly decreased after surgery, whereas the LL angle, SS, and AIH significantly increased (all p < 0.05). SP did not differ between the immediate postoperative period and the 3-month and final follow-up periods (p > 0.05). However, other parameters significantly improved during the follow-up period at all time points, except from 3 months to the final follow-up period (p > 0.05). Throughout the follow-up period, the lower back and leg pain VAS, ODI, and JOA scores considerably improved compared with the preoperative levels (p < 0.05). CONCLUSION: ULIF effectively treated lumbar spondylolisthesis with scoliosis, thereby reducing the degree of slip and scoliosis. By performing surgical reduction, fusion, and fixation only on the slipped segment, ULIF also had a corrective effect on the spinal lateral curvature, thereby avoiding the need for unnecessary scoliosis surgery. Moreover, the short-term efficacy was satisfactory, but the long-term efficacy requires further study.

Research on stem cell therapy for spinal cord injury: a bibliometric and visual analysis from 2018-2023.

Objectives: The aim of this study was to conduct a bibliometric analysis of the literature on stem cell treatment for spinal cord injury to gain an intuitive understanding of how the field is progressing, discover topics of interest, and determine what development trends are emerging in this field. Background: Spinal cord injury and its complications often cause an enormous economic burden, and postinjury repair and treatment have always been challenging in clinical and scientific research. Stem cell therapy for spinal cord injury can prevent immune rejection and induce the release of neuroprotective and anti-inflammatory factors to reduce the production of stress-related proteins, reactive oxygen species, and inflammatory reactions. Methods: We analyzed the number and quality of publications in the field of stem cell therapy in spinal cord injury between 2018.01.01 and 2023.06.30 in the core collection database of Web of Science. CiteSpace and VOSviewer were used to sort and summarize these studies by country, institution, authors' publications, and collaborative networks. In addition, the research topics of interest were identified and summarized. Results: This study ultimately included 2,150 valid papers, with the number of publications showing a gradual upward trend. The country, institution, author and journal with the greatest number of publications and citations are China, the Chinese Academy of Sciences, Dai JW, and the International Journal of Molecular Sciences, respectively. The top three high-frequency keyword clusters were hereditary paraplegia, reactive astrocytes and tissue engineering. Conclusion: With the help of visual analysis, we identified general trends and research topics of interest in the field of spinal cord injury over the last 5 years. Our findings suggest that stem cell transplantation for spinal cord injury and exosome therapy may be a focus of future research. This study provides a foundation for future research on stem cell therapy as well as clinical efforts in this field.

Cisplatin and doxorubicin chemotherapy alters gut microbiota in a murine osteosarcoma model.

The gut microbiota is closely associated with tumor progression and treatment in a variety of cancers. However, the alteration of the gut microbiota during the progression and chemotherapy of osteosarcoma remains poorly understood. This study aimed to explore the relationship between dysbiosis in the gut microbiota during osteosarcoma growth and chemotherapy treatment. We used BALB/c nude mice to establish osteosarcoma xenograft tumor models and administered cisplatin (CDDP) or doxorubicin (DOX) intraperitonially once every 2 days for a total of 5 times to establish effective chemotherapy models. Fecal samples were collected and processed for 16S rRNA sequencing to analyze the composition of the gut microbiota. We observed that the abundances of Colidextribacter, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG-010, Lachnospiraceae_UCG-006, and Lachnoclostridium decreased, and the abundances of Alloprevotella and Enterorhabdus increased in the osteosarcoma mouse model group compared to those in the control group. In addition, genera, such as Lachnoclostridium and Faecalibacterium were more abundant in chemotherapy-treated mice than those in saline-treated mice. Additionally, we observed that alterations in some genera, including Lachnoclostridium and Colidextribacter in the osteosarcoma animal model group returned to normal after CDDP or DOX treatment. Furthermore, the function of the gut microbiota was inferred through PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), which indicated that metabolism-related microbiota was highly enriched and significantly different in each group. These results indicate correlations between dysbiosis of the gut microbiota and osteosarcoma growth and chemotherapy treatment with CDDP or DOX and may provide novel avenues for the development of potential adjuvant therapies.

Computer-Assisted Navigation Full Visualization Spinal Endoscopic Surgery for Lumbar Vertebral Osteoid Osteoma.

BACKGROUND: Osteoid osteoma is a benign osteogenic tumor that occurs mostly in the femoral stem, while osteoid osteoma occurring in the lumbar vertebral body is a relatively rare case. To minimize treatment-related complications, a computer-assisted navigation fully visualized spinal endoscopy was used. Ultimately, the pathology was diagnosed as osteoid osteoma. CASE PRESENTATION: We report a 19-year-old adult male with low back pain that worsened at night and CT, MRI imaging showed an abnormal signal shadow at the posterior margin of the lumbar vertebral body. Due to the proximity of the lesion to the spinal canal and adjacent to the nerve roots, it was difficult to precisely localize the lesion by purely endoscopic or open procedures, and if necessary, the resection of surrounding tissues had to be expanded, causing unnecessary damage to the surrounding tissues. Therefore, we choose computer-assisted navigation fully visualized spinal endoscopy to perform the treatment. CONCLUSION: In this case, we report an osteoid osteoma that occurs less frequently in the lumbar vertebral body. Using computer-assisted navigation with fully visualized spinal endoscopy, we successfully resected the osteoid osteoma at the posterior margin of the L3 vertebral body preoperatively by computer-planned path with intraoperative visualization endoscopy, minimizing the damage to spinal stability. Computer-assisted navigation with visualization endoscopy provides a more precise and minimally invasive approach to the treatment of osteoid osteoma of the spine.

A bone implant with NIR-responsiveness for eliminating osteosarcoma cells and promoting osteogenic differentiation of BMSCs.

Incomplete removal of tumor cells and insufficient osseointegration are the main causes of bone tumor recurrence and implantation failure. In the present study, a multifunctional titanium-based bioactive implant for near-infrared-triggered synergy therapy to overcome these hurdles is engineered, composed of titanium dioxide (TiO2) nanoparticles doped with fluorine (F)/dopamine (PDA)/collagen. The TiO2 nanoparticles designed in this work can simultaneously exhibit excellent near-infrared-activated photothermal and photocatalytic properties. Besides, the layer designed in this work show excellent anti-tumor activity under irradiation with 808 nm light due to the synergetic effect of hyperthermia and reactive oxygen species (ROS), and Saos-2 cells can be eradicated within 10 min. Moreover, modification of PDA and collagen endue the Ti alloy excellent osteogenic activity.

Periostin promotes the proliferation and metastasis of osteosarcoma by increasing cell survival and activates the PI3K/Akt pathway.

BACKGROUND: Silencing of the periostin gene (POSTN) can inhibit the biological process of several different cancers, and this inhibition may be related to down-regulation of PI3K/AKT signaling. However, the effect of POSTN on the progression, proliferation, and invasion of osteosarcoma (OS) remain unclear. METHODS: We used the Gene Expression Omnibus (GEO) database to screen datasets on in situ OS and lung metastases to identify core genes and potential pathways. We used additional bioinformatics tools to identify protein-protein interactions (PPIs) and gene networks, and selected the top seven genes whose expression had the strongest correlations with other genes. RESULTS: The results indicated that POSTN was a major hub gene. Subsequent analysis of gene expression profiles showed that POSTN was highly expressed in 262 cases with sarcoma and expression was closely related to poor prognosis. We also performed enrichment analysis to identify differentially expressed genes and used real-time PCR, western blotting, and immunohistochemistry analyses to measure POSTN expression in cells and tissues. Transfection of a POSTN-shRNA plasmid into cultured OS cells (Saos-2) effectively inhibited the proliferation, invasion, and migration of these cells. Taken together, our results suggest that POSTN may play a role in promoting the proliferation and metastasis of OS by activation of the PI3K/Akt signaling pathway. CONCLUSIONS: Our results provide a preliminary characterization of the mechanism by which POSTN may regulate the migration and invasion of OS cells and also provide a theoretical basis for identifying biomarkers that have potential use for the diagnosis and treatment of OS.

Diverse autophagy and apoptosis in myeloid leukemia cells induced by 20(s)-GRh2 and blue LED irradiation.

Autophagy is an important mechanism for cell death regulation. To improve the anticancer effect during the treatment of leukemia and promote the apoptosis of leukemic cells, it is important to define the relationship between autophagy and apoptosis. A key bioactive compound in traditional Chinese medicine, 20(s)-Ginsenoside (GRh2), demonstrated an advancement in leukemia treatment. Blue LED therapy (BL) is a physical treatment method that can induce leukemic cell death. In this study, we tested the effect of 20(s)-GRh2, BL, and their combination (BL-GRh2) on the activation of leukemic cell apoptosis and autophagy. Both treatments, whether used individually or simultaneously, induce apoptosis through the induction of reactive oxygen species (ROS), disrupted mitochondrial membrane potential (MMP) and regulated the expression of apoptosis-related genes and proteins. Furthermore, using western blotting to analyze the autophagy markers LC3B and P62, we detected the activation of autophagy. In cells treated with autophagy inhibitor 3-MA, both autophagy and apoptosis were inhibited, either by BL alone or by BL-GRh2. However, apoptosis in 20(s)-GRh2-treated cells was enhanced. In cells treated with apoptosis suppressor Z-VAD-FMK, autophagy was inhibited in the BL and BL-GRh2-treated cells, although it was enhanced in cells treated with 20(s)-GRh2 alone. Moreover, we observed a stronger induction of apoptosis by BL-GRh2 in myeloid leukemia cells. Our data indicate that autophagy induced by different factors can play diverse roles on the same cells. Our results also indicate that the combination of traditional Chinese medicine with physical therapy may be a new strategy for anti-cancer therapy.

20(S)-Ginsenoside Rh2 Induce the Apoptosis and Autophagy in U937 and K562 Cells.

Acute myeloid leukemia (AML) and Chronic myelogenous leukemia (CML) are common leukemia in adults. 20(S)-GRh2 is an important bioactive substance that is present in Panax ginseng. However, there are no investigations that deal with the comparison of apoptosis, the occurrence of autophagy, and the relationship between apoptosis and autophagy after being treated with 20(S)-GRh2 in AML and CML. In this study, we explored the effect of 20(S)-GRh2 on the AML and CML (U937 and K562). Fluorescence microscopy, CCK-8, Quantitative realtime PCR, Western blot, transmission electron microscopy (TEM), and flow cytometric analysis were used to detect the occurrence of cell proliferation inhibition, apoptosis, and autophagy. By using the above methods, it was determined that apoptosis induced by 20(S)-GRh2 was more obvious in K562 than U937 cells and 20(S)-GRh2 could generate autophagy in K562 and U937 cells. When pretreated by a specific inhibitor of autophagy, (3-methyladenine), the 20(S)-GRh2-induced apoptosis was enhanced, which indicated that 20(S)-GRh2-induced autophagy may protect U937 and K562 cells from undergoing apoptotic cell death. On the other hand, pretreated by an apoptosis suppressor (Z-VAD-FMK), it greatly induced the autophagy and partially prevented 20(S)-GRh2 induced apoptosis. This phenomenon indicated that 20(S)-GRh2-induced autophagy may serve as a survival mechanism and apoptosis and autophagy could act as partners to induce cell death in a cooperative manner. These findings may provide a rationale for future clinical application by using 20(S)-GRh2 combined autophagy inhibitors for AML and CML.

Expression of b-FGF and endostatin and their clinical significance in human osteosarcoma.

OBJECTIVE: To investigate the expression and the clinical significance of basic fibroblast growth factor (b-FGF) and endostatin in osteosarcoma. METHODS: From January 2003 to December 2005, expression of b-FGF, endostatin and CD34 were detected in 30 osteosarcoma and 30 osteochondroma tissue specimens by the immunohistochemical Elivision method. All data were post-processed with SPSS 13.0 software and prepared for investigation and analysis of these expressions and the relationships between the parameters. RESULTS: (i) The rates of expression of b-FGF, endostatin and CD34 protein in osteosarcoma were 76.7%, 93.3%, and 96.7%, respectively, and in osteochondroma 43.3%, 40.0% and 16.7%, respectively. Each of the three expressions showed obvious differences between the osteosarcoma and the osteochondroma group. (ii) In the osteosarcoma group, expression of endostatin was positively correlated with that of CD34 (P < 0.05, γs = 0.528), and expression of endostatin in poorly differentiated osteosarcoma was much greater than that in highly differentiated osteosarcoma (P= 0.004). Expression of endostatin correlated with osteosarcoma metastasis (P= 0.036). (iii) There was no correlation between b-FGF and endostatin expression rates (P= 0.182) in the osteosarcoma group. CONCLUSION: Angiogenesis is the basis of tumor metastasis, as well as being an important factor in tumor growth. Expression of endostatin could be adopted as a parameter for the diagnosis of postoperative metastases and for assessing prognosis, and could act as an adjuvant indicator in the grading of osteosarcoma.

[Operative strategy of atlantoaxial instability].

OBJECTIVE: To evaluate the operative strategy and therapeutic outcomes of the atlantoaxial instability. METHODS: Clinical data of 29 patients with atlantoaxial instability were retrospectively analyzed. There were 27 males and 2 females. The mean age was 33 years old with a range from 18 to 54 years. There were fracture of anterior arch of atlas accompanied with ligamentum transversum rupture in 5 cases, odontiod fracture in 7 cases, Hangman fracture in 6 cases, dysplasia of atlas and axis in 10 cases, ankylosing spondylitis in 1 case. The clinical and imaging manifestation of atlantoaxial instability were found in all patients. The symptoms and physical signs of superior cervical spinal cord disease or cervical spinal injury were found in 18 cases. The patients were treated with simple modified Magerl method (7 cases), cannutated screw fixation(6 cases), resection of C2,3 disc throuth the anterior approach and fusion with Zephir titanium plate (4 cases), percutaneous pedicle screw fixation of C2 (2 cases), release and reduction through anterior oropharynx (LRAO) combined with modified Magerl method (4 cases), LRAO and atlas lateral mass screw and plate fixation through posterior approach (3 cases), cervical occipital fusion through C2 pedicle (3 cases). RESULTS: All patients were followed up with an average time of 17.2 months ranging from 11 to 38 months. All patients obtained anatomical reduction and bone healing. Using Odom standard to evaluation for 18 cases with spinal injury before operation, the results were excellent in 9 cases,good in 7,fair in 2. No injury of vertebral artery, nerve root, spinal cord, infection of incisional wound, breaking or loosening of internal fixatir were found in the study. CONCLUSION: Identifying the causes of atlantoaxial instability, rational plan of operation can get satisfactory clinical results.