YBX-1 alleviates sepsis-stimulated lung epithelial cell injury.

OBJECTIVE: To explore the role of Y-box binding protein 1 (YBX-1) in the lipopolysaccharide (LPS)-stimulated inflammation and oxidative stress of BEAS-2B cell line and clarify the underlying mechanism. METHODS: LPS-stimulated BEAS-2B cells were used as a cell model of sepsis-stimulated acute lung injury (ALI). Immunoblot and quantitative polymerase chain reaction assays were used to detect the expression of YBX-1 in LPS-stimulated BEAS-2B cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, TdT-mediated dUTP nick end labeling, and immunoblot assays were conducted to determine the effects of YBX-1 on cell survival. JC-1 staining and adenosine triphosphate production were used to detect the effects of YBX-1 on mitochondrial function. Immunostaining and enzyme-linked immunosorbent serologic assay were performed to examine the effects of YBX-1 on the inflammation and oxidative stress of cells. Immunoblot assay was conducted to confirm the mechanism. RESULTS: YBX-1 was lowly expressed in LPS-stimulated BEAS-2B cells and enhanced the survival of LPS-stimulated lung epithelial cells. In addition, YBX-1 improved mitochondrial function of LPS-stimulated BEAS-2B cells. YBX-1 inhibited the inflammation and oxidative stress of LPS-stimulated BEAS-2B cells. Mechanically, YBX-1 inhibited mitogen-activated protein kinase (MAPK) axis, thereby alleviating sepsis-stimulated ALI. CONCLUSION: YBX-1 alleviated inflammation and oxidative stress of LPS-stimulated BEAS-2B cells via MAPK axis.

YBX-1 alleviates sepsis-stimulated lung epithelial cell injury

Objective: To explore the role of Y-box binding protein 1 (YBX-1) in the lipopolysaccharide (LPS)-stimulated inflammation and oxidative stress of BEAS-2B cell line and clarify the underlying mechanism. Methods: LPS-stimulated BEAS-2B cells were used as a cell model of sepsis-stimulated acute lung injury (ALI). Immunoblot and quantitative polymerase chain reaction assays were used to detect the expression of YBX-1 in LPS-stimulated BEAS-2B cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, TdT-mediated dUTP nick end labeling, and immunoblot assays were conducted to determine the effects of YBX-1 on cell survival. JC-1 staining and adenosine triphosphate production were used to detect the effects of YBX-1 on mitochondrial function. Immunostaining and enzyme-linked immunosorbent serologic assay were performed to examine the effects of YBX-1 on the inflammation and oxidative stress of cells. Immunoblot assay was conducted to confirm the mechanism. Results: YBX-1 was lowly expressed in LPS-stimulated BEAS-2B cells and enhanced the survival of LPS-stimulated lung epithelial cells. In addition, YBX-1 improved mitochondrial function of LPS-stimulated BEAS-2B cells. YBX-1 inhibited the inflammation and oxidative stress of LPS-stimulated BEAS-2B cells. Mechanically, YBX-1 inhibited mitogen-activated protein kinase (MAPK) axis, thereby alleviating sepsis-stimulated ALI. Conclusion: YBX-1 alleviated inflammation and oxidative stress of LPS-stimulated BEAS-2B cells via MAPK axis. (AU)

Circulating IGFBP-3 and Interleukin 6 as Predictors of Osteoporosis in Postmenopausal Women: A Cross-Sectional Study.

Objective: To explore the relationship between circulating IGFBP-3, IL-6, and bone mineral density and the potential diagnostic role of circulating IGFBP-3 and IL-6 in postmenopausal women with osteoporosis. Methods: Eighty-five postmenopausal women at Soochow University's First Affiliated Hospital, Osteoporosis and Menopause Clinics, were recruited. Forty-five of 85 women were diagnosed with osteoporosis. Circulating IL-6, PTH, 1,25(OH)2D3, osteocalcin (OST), IGF-1, IGFBP-3, and bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) were measured in 40 ordinary and 45 osteoporotic women. A simple regression analysis calculated the correlation between age, BMD, IL-6, and IGFBP-3. Multiple stepwise regression analyses were conducted to determine which variables were independently related to BMD. The potential role of IGFBP-3 and IL-6 in the diagnosis of postmenopausal osteoporosis was predicted using the area under the receiver operating characteristic curve (ROC, AUC). Results: Age, years since menopause, and circulating IL-6, PTH, and IGFBP-3 were significantly higher in the osteoporosis group compared to the normal group. Osteoporotic women had substantially lower BMDs of the LS and FN than normal women. Age-related increases were found for IGFBP-3 and IL-6, whereas age-related decreases were observed for LS/FN BMD. IGFBP-3 and IL-6 were both negatively correlated with LS and FN BMD. Stepwise multiple regression analysis showed that IGFBP-3 and IL-6 were strong predictors of BMD in postmenopausal women. AUC cut-off values (IGFBP-3: 3.65, IL-6: 0.205) were best evaluated for the diagnosis of postmenopausal women with osteoporosis, and the AUC for circulating IGFBP-3 and IL-6 were 0.706 (95% CI 0.594-0.818) and 0.685 (95% CI 0.571-0.798), respectively. Conclusion: In this cross-sectional study of postmenopausal women, IGFBP-3 and IL-6 were negatively related to BMD. Circulating IGFBP-3 and IL-6 might be essential predictors of postmenopausal osteoporosis and can help predict osteoporotic fracture.

Clinical Efficacy of Percutaneous Kyphoplasty Combined with Calcitriol and Calcium in the Treatment of Traumatic Nonosteoporotic Vertebral Compression Fractures.

Objective: The present study investigated the clinical efficacy of percutaneous kyphoplasty (PKP) combined with calcitriol and calcium in the treatment of traumatic nonosteoporotic vertebral compression fractures (TNVCFs). Methods: The patients were equally divided into a control group and a treatment group by a random number table. The patients in the control group underwent PKP surgery, and the patients in the treatment group received calcitriol and calcium on the basis of PKP surgery. The visual analog scale (VAS) pain scores, Oswestry Disability Index (ODI) scores, the height of the anterior edge of the vertebral body, Cobb's angle, and the level of the bone mineral density of the two groups of TNVCF patients before surgery were recorded and compared, one and six months after surgery. Results: Thirty-six inpatients with TNVCFs admitted to the trauma center of the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were recruited. There were no significant differences in the VAS and ODI scores, the height of the anterior edge of the injured vertebral body, Cobb's angle, and bone mineral density between the two groups before surgery (P > 0.05). The VAS scores, ODI scores, the height of the anterior edge of the injured vertebral body, and Cobb's angle of the two groups of patients after surgery were significantly better than those before surgery. One and six months after surgery, the VAS and ODI scores, the height of the anterior edge of the injured vertebral body, Cobb's angle, and the bone mineral density of the patients in the treatment group improved significantly compared to those in the control group (P < 0.05). Conclusions: PKP combined with calcitriol and calcium medications could significantly relieve pain, alleviate the loss of compressed vertebral height and kyphosis, and improve the spinal function and the life quality of the TNVCF patients.

Corrigendum to "Salvianolic Acid B Protects Intervertebral Discs from Oxidative Stress-Induced Degeneration via Activation of the JAK2/STAT3 Signaling Pathway".

[This corrects the article DOI: 10.1155/2021/6672978.].

Similarity and difference between aging and puncture-induced intervertebral disc degeneration.

The purpose of our study was to investigate the changes in micromorphology and mechanical properties of intervertebral discs degeneration induced by aging and puncture. Normal group (NG), 2 weeks post-puncture degeneration group (PDG) and aging degeneration group (ADG) each included 10 rats. Plain film, magnetic resonance imaging, and histological testing were utilized to assess intervertebral disc degeneration. Atomic force microscope was utilized to analyze the microstructure and elastic modulus of the intervertebral disc, while immunohistochemistry was employed to assess alterations in the cell matrix using collagen I, collagen II, matrix metalloproteinase-3 (MMP-3), and tumour necrosis factor-α (TNF-α). The results showed that the disc height ratio between PDG and ADG decreased. In the PDG and ADG group, histological scores both increased, the gray value of the T2 signal decreased, the proportion of MMP-3 and TNF-positive cells in intervertebral disc tissues was higher (p < 0.05) and the IOD values of COL-2 lower in intervertebral disc tissues (p < 0.05). The elastic modulus of PDG and ADG annulus fibers (AF) increased compared to the NG (p < 0.05); when compared to PDG, the elastic modulus of ADG AF decreased (p < 0.05). The elastic modulus of PDG and ADG collagen increased in the nucleus pulposus (NP, p < 0.05); ADG had a greater AF diameter than NG and PDG (p < 0.05). The results indicated that ADG fiber diameter thickens, and chronic inflammation indicators rise; PDG suffers from severe extracellular matrix loss. The degeneration of the ADG and PDG intervertebral discs is different. The results provide foundation for clinical research.

Sodium Tanshinone IIA Sulfonate Ameliorates Injury-Induced Oxidative Stress and Intervertebral Disc Degeneration in Rats by Inhibiting p38 MAPK Signaling Pathway.

OBJECTIVE: Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA, a representative traditional Chinese medicine. The aim of the study was to investigate the capability of STS to reverse injury-induced intervertebral disc degeneration (IDD) and explore the potential mechanisms. METHODS: Forty adult rats were randomly allocated into groups (control, IDD, STS10, and STS20). An IDD model was established by puncturing the Co8-9 disc using a needle. Rats in the STS groups were administered STS by daily intraperitoneal injection (10 or 20 mg/kg body weight) while rats in the control and IDD groups received the same quantity of normal saline. After four weeks, the entire spine from each rat was scanned for X-ray and MRI analysis. Each Co8-9 IVD underwent histological analysis (H&E, Safranin-O Fast green, and alcian blue staining). A tissue was analyzed by immunohistochemical (IHC) staining to determine the expression levels of collagen II (COL2), aggrecan, matrix metalloproteinase-3/13 (MMP-3/13), interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α). Levels of oxidative stress were measured using an ELISA while activity of the p38 MAPK pathway was assessed using Western blot analysis. RESULTS: Compared with the control group, needle puncture significantly decreased IVD volume and T-2 weighted MR signal intensity, confirming disc degeneration. These alterations were significantly attenuated by treatment with 10 or 20 mg/kg STS. Lower COL2 and aggrecan and higher MMP-3/13, IL-1ß, IL-6, and TNF-α levels in the IDD group were substantially reversed by STS. In addition, treatment with STS increased antioxidative enzyme activity and decreased levels of oxidative stress induced by needle puncture. Furthermore, STS inhibited the p38 MAPK pathway in the rat model of IDD. CONCLUSIONS: STS ameliorated injury-induced intervertebral disc degeneration and displayed anti-inflammatory and antioxidative properties in a rat model of IDD, possibly via inhibition of the p38 MAPK signaling pathway.

Salvianolic Acid B Protects Intervertebral Discs from Oxidative Stress-Induced Degeneration via Activation of the JAK2/STAT3 Signaling Pathway.

OBJECTIVE: To evaluate the influence of salvianolic acid B (SAB), an antioxidant derived from Danshen, on intervertebral disc degeneration (IDD) and its possible molecular mechanisms. METHODS: Sixty adult rats were randomly grouped (control, IDD, and SAB IDD groups). IDD was induced using needle puncture. The rats received daily administration of SAB (20 mg/kg) in the SAB IDD group while the other two groups received only distilled water. The extent of IDD was evaluated using MRI after 3 and 6 weeks and histology after 6 weeks. Oxidative stress was assessed using the ELISA method. In in vitro experiments, nucleus pulposus cells (NPCs) were treated with H2O2 (100 µM) or SAB+H2O2, and levels of oxidative stress were measured. Cell apoptosis was assessed by flow cytometry, expression levels of Bcl-2, Bax, and cleaved caspase-3 proteins. Cell proliferation rate was assessed by EdU analysis. Pathway involvement was determined by Western blotting while the influence of the pathway on NPCs was explored using the pathway inhibitor AG490. RESULTS: The data demonstrate that SAB attenuated injury-induced IDD and oxidative stress, caused by activation of the JAK2/STAT3 signaling pathway in vivo. Oxidative stress induced by H2O2 was reversed by SAB in vitro. SAB reduced the increased cell apoptosis, cleaved caspase-3 expression, and caspase-3 activity induced by H2O2. Reduced cell proliferation and decreased Bcl-2/Bax ratio induced by H2O2 were rescued by SAB. Additionally, the JAK2/STAT3 pathway was activated by SAB, while AG490 counteracted this effect. CONCLUSION: The results suggest that SAB protects intervertebral discs from oxidative stress-induced degeneration by enhancing proliferation and attenuating apoptosis via activation of the JAK2/STAT3 signaling pathway.

Percutaneous vertebroplasty versus kyphoplasty for the treatment of neurologically intact osteoporotic Kümmell's disease.

BACKGROUND: Percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) have been widely used to treat neurologically intact osteoporotic Kümmell's disease (KD), but it is still unclear which treatment is more advantageous. Our study aimed to compare and investigate the safety and clinical efficacy of PVP and PKP in the treatment of KD. METHODS: The relevant data that 64 patients of neurologically intact osteoporotic KD receiving PVP (30 patients) or PKP (34 patients) were analyzed. Surgical time, operation costs, intraoperative blood loss, volume of bone cement injection, and fluoroscopy times were compared. Occurrence of cement leakage, transient fever and re-fracture were recorded. Universal indicators of visual analogue scale (VAS) and Oswestry disability index (ODI) were evaluated separately before surgery and at 1 day, 6 months, 1 year, 2 years and the final follow-up after operation. The height of anterior edge of the affected vertebra and the Cobb's angle were assessed by imaging. RESULTS: All patients were followed up for at least 24 months. The volume of bone cement injection, intraoperative blood loss, occurrence of bone cement leakage, transient fever and re-fracture between two groups showed no significant difference. The surgical time, the operation cost and fluoroscopy times of the PKP group was significantly higher than that of the PVP group. The post-operative VAS, ODI scores, the height of the anterior edge of the injured vertebrae and kyphosis deformity were significantly improved in both groups compared with the pre-operation. The improvement of vertebral height and kyphosis deformity in PKP group was significantly better than that in the PVP group at every same time point during the follow-up periods, but the VAS and ODI scores between the two groups showed no significant difference. CONCLUSION: PVP and PKP can both significantly alleviate the pain of patients with KD and obtain good clinical efficacy and safety. By contrast, PKP can achieve better imaging height and kyphosis correction, while PVP has the advantages of shorter operation time, less radiation volume and operation cost.

Apolipoprotein C1 (APOC1): A Novel Diagnostic and Prognostic Biomarker for Cervical Cancer.

BACKGROUND: Previous reports showed that APOC1 was associated with several cancers but the function of APOC1 in cervical cancer was unknown. This study aimed to investigate the clinical effect and function of APOC1 in cervical cancer. MATERIALS AND METHODS: In this study, the relative expression of APOC1 in cervical cancer was detected by RT-qPCR. In order to determine the cell proliferation and migration and invading ability and apoptosis more accurately, we used CCK8 assay, Edu assay, wound healing assay, migration and invasion assay, flow cytometry assay, co-immunoprecipitation, proteomics and Western blot by silencing and overexpressing APOC1, respectively. The role of APOC1 on tumor progression was explored in vitro and vivo. RESULTS: The relative expression of APOC1 in cervical cancer tissues was up-regulated (P<0.05). In cervical cancer cell lines, silencing of APOC1 restrained cell progression and EMT, while over-expression of APOC1 accelerated cell progression and EMT in vivo and vitro (P<0.05). CONCLUSION: APOC1 acts as an oncogene in cervical cancers and knockdown of APOC1 inhibited cervical cancer cells growth in vitro and in vivo. There is a close relationship between the relative expression of APOC1 and clinical outcome in cervical cancer patients.

Increased elastic modulus of the synovial membrane in a rat ACLT model of osteoarthritis revealed by atomic force microscopy.

This study aimed to explore changes in nanoscale elastic modulus of the synovium using atomic force microscopy (AFM) in addition to investigate changes in synovial histomorphology and secretory function in osteoarthritis (OA) in a rat anterior cruciate ligament transection (ACLT) model. Sprague-Dawley rats were randomly assigned to sham control and ACLT OA groups. All right knee joints were harvested at 4, 8, or 12 weeks (W) after surgery for histological assessment of cartilage damage and synovitis in both the anterior and posterior capsules. AFM imaging and nanoscale biomechanical testing were conducted to measure the elastic modulus of the synovial collagen fibrils. Immunohistochemistry was used to visualize the expression of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-3 (MMP-3) in the synovium. The OA groups exhibited progressive development of disease in the cartilage and synovium. Histopathological scores of the synovium in the OA groups increased gradually. Significant differences were observed between all OA groups except for the posterior 4W group. The synovial fibril arrangement in all OA groups was significantly disordered. The synovial fibrils in all ACLT OA groups at each time point were stiffer than those in the sham controls. OA rats displayed a significantly higher expression of IL-1ß and MMP3 in the anterior capsule. In summary, synovial stiffening was closely associated with joint degeneration and might be a factor contributing to synovitis and increased production of proinflammatory mediators. Our data provided insights into the role of synovitis, particularly stiffening of the synovium, in OA pathogenesis.

Danshen Attenuates Intervertebral Disc Degeneration via Antioxidation in SD Rats.

OBJECTIVE: To investigate the effects of Danshen on the imaging and histological parameters, expression levels of ECM-associated proteins and inflammatory factors, and antioxidative activity in the degenerated intervertebral disc (IVD) of SD rats. METHODS: Sixty male rats were randomly divided into three groups (control, IDD, and Danshen IDD). Percutaneous needle puncture in Co8-9 intervertebral disc was conducted in all rats of the IDD and Danshen IDD groups to induce intervertebral disc degeneration (IDD). After operation, animals of the Danshen IDD group were administrated with Danshen granules (3 g/kg body weight ) by gavage once a day. Four weeks later, the coccygeal vertebrae were harvested and used for imaging (disc height and MR signal), histological, immunohistochemical, and biochemical [water content, glycosaminoglycans (GAG), superoxide dismutase (SOD2), glutathione (GSH), and malondialdehyde (MDA)] analyses. RESULTS: The puncture induced significant decreased IVD space and MR T2 signal at both 2 and 4 weeks, which were attenuated by Danshen treatment. The disc degeneration in the IDD group (HE and Safranin O-Fast Green histological staining was markedly more serious compared with that in the control group. Four weeks of Danshen treatment significantly alleviated this degeneration compared with the IDD group. Needle puncture resulted in the upregulation of IL-1ß and TNF-α, MMP-3, and downregulation of COL2 and aggrecan in the IDD group. However, this change was significantly weakened by Danshen treatment. Significantly lower water and GAG content, as well as the SOD2 and GSH levels, in the IDD group were found compared with those in the control group. However, the above parameters of the Danshen IDD group were significantly higher than those of the IDD group. Danshen treatment significantly decreased the content of MDA which was increased by needle puncture in the IDD group. CONCLUSION: Danshen can attenuate intervertebral disc degeneration in SD rats by suppressing the oxidation reaction.

Increased elastic modulus of the synovial membrane in a rat ACLT model of osteoarthritis revealed by atomic force microscopy

This study aimed to explore changes in nanoscale elastic modulus of the synovium using atomic force microscopy (AFM) in addition to investigate changes in synovial histomorphology and secretory function in osteoarthritis (OA) in a rat anterior cruciate ligament transection (ACLT) model. Sprague-Dawley rats were randomly assigned to sham control and ACLT OA groups. All right knee joints were harvested at 4, 8, or 12 weeks (W) after surgery for histological assessment of cartilage damage and synovitis in both the anterior and posterior capsules. AFM imaging and nanoscale biomechanical testing were conducted to measure the elastic modulus of the synovial collagen fibrils. Immunohistochemistry was used to visualize the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-3 (MMP-3) in the synovium. The OA groups exhibited progressive development of disease in the cartilage and synovium. Histopathological scores of the synovium in the OA groups increased gradually. Significant differences were observed between all OA groups except for the posterior 4W group. The synovial fibril arrangement in all OA groups was significantly disordered. The synovial fibrils in all ACLT OA groups at each time point were stiffer than those in the sham controls. OA rats displayed a significantly higher expression of IL-1β and MMP3 in the anterior capsule. In summary, synovial stiffening was closely associated with joint degeneration and might be a factor contributing to synovitis and increased production of proinflammatory mediators. Our data provided insights into the role of synovitis, particularly stiffening of the synovium, in OA pathogenesis.