The Different Influence of Cutibacterium Acnes and Staphylococcus Epidermidis in the Lumbar Disc: An in Vivo Study in Rabbits.

STUDY DESIGN: Animal laboratory study. OBJECTIVE: This study investigated the effects of C. acnes and S. epidermidis on the lumbar discs of rabbits, as well as the outcomes of combined infection. SUMMARY OF BACKGROUND DATA: Many studies have indicated that bacterial infections are associated with lumbar disc degeneration (LDD). The most commonly cultured bacteria from disc tissues are Cutibacterium acne (C. acnes) and Staphylococcus epidermidis (S. epidermidis). METHODS: New Zealand white rabbits (n=40) were randomly divided into control, C. acnes, S. epidermidis, and C. acnes plus S. epidermidis (i.e., combined) groups. All groups except the control were injected with 25 µL of saline at L4-L5 and 25 µL of bacteria (1×107 CFU/mL) at L5-L6. All injections were performed under X-ray guidance. Weight measurements, haematological evaluations, and magnetic resonance imaging were performed after 4, 8, and 12 weeks. Histological examination and gene expression detection were performed 12 weeks after surgery. RESULTS: Inflammatory factors in the blood and weight did not differ among the groups after 4, 8, and 12 weeks (P >0.05). However, after 4 weeks, LDD occurred in the C. acnes group, and discitis occurred in the S. epidermidis and combined groups, all of which worsened after 8 weeks. After 12 weeks, the nucleus pulposus (NP) protruded and compressed the spinal cord in the C. acnes group, and tissue staining showed decreased NP tissue and cartilaginous endplate fracture. In the S. epidermidis and combined groups, the discitis was more confined, but tissue staining revealed a significant decrease in NP tissue, and loss of the normal disc structure. CONCLUSIONS: In the early stage of infection in rabbits, C. acnes caused LDD, and S. epidermidis caused discitis. Co-infection with C. acnes and S. epidermidis caused discitis but was more limited in scope than infection with S. epidermidis alone.

S100A6 Regulates nucleus pulposus cell apoptosis via Wnt/ß-catenin signaling pathway: an in vitro and in vivo study.

BACKGROUND: Intervertebral disc degeneration (IDD) is a common musculoskeletal degenerative disease, which often leads to low back pain and even disability, resulting in loss of labor ability and decreased quality of life. Although many progresses have been made in the current research, the underlying mechanism of IDD remains unclear. The apoptosis of nucleus pulposus (NP) cells (NPCs) is an important pathological mechanism in intervertebral disc degeneration (IDD). This study evaluated the relationship between S100A6 and NPCs and its underlying mechanism. METHODS: Mass spectrometry, bioinformatics, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were used to screen and verify hub genes for IDD in human IVD specimens with different degeneration degrees. Western blotting, immunohistochemistry (IHC), and/or immunofluorescence (IF) were used to detect the expression level of S100A6 in human NP tissues and NPCs. The apoptotic phenotype of NPCs and Wnt/ß-catenin signaling pathway were evaluated using flow cytometry, western blotting, and IF. S100A6 was overexpressed or knocked down in NPCs to determine its impact on apoptosis and Wnt/ß-catenin signaling pathway activity. Moreover, we used the XAV-939 to inhibit and SKL2001 to activate the Wnt/ß-catenin signaling pathway. The therapeutic effect of S100A6 inhibition on IDD was also evaluated. RESULTS: S100A6 expression increased in IDD. In vitro, increased S100A6 expression promoted apoptosis in interleukin (IL)-1ß-induced NPCs. In contrast, the inhibition of S100A6 expression partially alleviated the progression of annulus fibrosus (AF) puncture-induced IDD in rats. Mechanistic studies revealed that S100A6 regulates NPC apoptosis via Wnt/ß-catenin signaling pathway. CONCLUSIONS: This study showed that S100A6 expression increased during IDD and promoted NPCs apoptosis by regulating the Wnt/ß-catenin signaling pathway, suggesting that S100A6 is a promising new therapeutic target for IDD.

Identification of Autophagy-Related Genes Involved in Intervertebral Disc Degeneration by Microarray Data Analysis.

BACKGROUND: Nucleus pulposus cells survive in a hypoxic, acidic, nutrient-poor, and hypotonic microenvironment. Consequently, they maintain low proliferation and undergo autophagy to protect themselves from cellular stress. Therefore, we aimed to identify autophagy-related biomarkers involved in intervertebral disc degeneration pathogenesis. METHODS: Autophagy-related differentially expressed genes were derived from the intersection between the public GSE147383 microarray data set to identify differentially expressed genes and online databases to identify autophagy-related genes. Furthermore, we assessed their biological functions with gene annotation and enrichment analysis in the Metscape portal. Then, the STRING database and Cytoscape software allowed inferring a protein-protein interaction (PPI) network and identifying hub genes. In addition, to predict transcription factors that may regulate the hub genes, we used the GeneMANIA website. Finally, the competing endogenous RNA prediction tools and Cytoscape were also used to construct an mRNA-miRNA-lncRNA network. RESULTS: A total of 123 autophagy-related differentially expressed genes were identified, they were mainly involved in phosphoinositide 3-kinase-Akt signaling, autophagy animal, and apoptosis pathways. Nine were identified as hub genes (PTEN, MYC, CTNNB1, JUN, BECN1, ERBB2, FOXO3, ATM, and FN1) and 36 transcription factors were associated with them. Finally, an autophagy-associated competing endogenous RNA network was constructed based on the 9 hub genes. CONCLUSIONS: Nine hub genes were identified and a network of competing endogenous RNA associated with autophagy was established. They can be used as autophagy-related biomarkers of intervertebral disc degeneration and for further exploration.

HSP70 protects PC12 cells against TBHP-induced apoptosis and oxidative stress by activating the Nrf2/HO-1 signaling pathway.

HSP70 exhibits neuroprotective, antioxidant, and anti-apoptotic properties, which are crucial in preventing spinal cord injury (SCI) induced by oxidative stress and apoptosis. In this study, we assessed the potential protective effects and underlying mechanisms of HSP70 on tert-butyl hydroperoxide (TBHP)-damaged PC12 cells in an in vitro model of SCI. To establish the model, PC12 cells were subjected to oxidative damage induced by TBHP, followed by overexpression of HSP70. Cell viability was assessed using the CCK8 kit, intracellular reactive oxygen species level was evaluated using a commercial kit, cell apoptosis was detected using the Annexin V-APC/7-ADD Apoptosis Detection Kit, and the oxidative stress level was determined using SOD and MDA assay kits. Western blot analysis was used to detect the expression levels of Bax, cleaved caspase-3, and Bcl-2 proteins. Furthermore, immunofluorescence staining and Western bolt were used to detect the expression levels of proteins associated with the Nrf2/HO-1 signaling pathway. We found that HSP70 overexpression reduced apoptosis and oxidative stress in TBHP-induced PC12 cells. Furthermore, it activated the Nrf2/HO-1 signaling pathway. In addition, the Nrf2 inhibitor ML385 attenuated the protective effects of HSP70 on TBHP-induced PC12 cells. In conclusion, HSP70 can partially alleviate TBHP-induced apoptosis and oxidative stress in PC12 cells by promoting the Nrf2/HO-1 signaling pathway.

siRNA incorporated in slow-release injectable hydrogel continuously silences DDIT4 and regulates nucleus pulposus cell pyroptosis through the ROS/TXNIP/NLRP3 axis to alleviate intervertebral disc degeneration.

Aims: In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods: An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel's mechanism in IVDD. Results: A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion: DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD.

The Role of S100A6 in Human Diseases: Molecular Mechanisms and Therapeutic Potential.

S100A6, also known as calcyclin, is a low-molecular-weight Ca2+-binding protein from the S100 family that contains two EF-hands. S100A6 is expressed in a variety of mammalian cells and tissues. It is also expressed in lung, colorectal, pancreatic, and liver cancers, as well as other cancers such as melanoma. S100A6 has many molecular functions related to cell proliferation, the cell cycle, cell differentiation, and the cytoskeleton. It is not only involved in tumor invasion, proliferation, and migration, but also the pathogenesis of other non-neoplastic diseases. In this review, we focus on the molecular mechanisms and potential therapeutic targets of S100A6 in tumors, nervous system diseases, leukemia, endometriosis, cardiovascular disease, osteoarthritis, and other related diseases.

Bioinformatics Analysis of Programmed Cell Death in Spinal Cord Injury.

BACKGROUND: Programmed cell death (PCD) in the development of spinal cord injury (SCI) is complicated, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, and autophagy. It is necessary to make clear the expression levels of PCD and potential molecular targets after SCI for formulating relevant treatment strategies. METHODS: We downloaded the rats' SCI expression matrix GSE45006, and the ssGSEA method was used to analyze the PCD after SCI. Then the related differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and pathway analysis, protein-protein interaction (PPI) network construction, and HUB genes were identified. Finally, the correlation between HUB genes and PCD was analyzed. RESULTS: Apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy increased significantly in acute SCI, and then decreased gradually in the subacute and chronic stages; cuproptosis in acute SCI decreased significantly, and then gradually increased. In addition, we also screened 116 DEGs during the development of SCI. GO and pathway analysis showed that DEGs was related to mitosis and cell cycle. The identified hub genes are closely related to cell apoptosis, necroptosis, pyroptosis, ferroptosis after injury, and autophagy. CONCLUSIONS: PCD occurs differently in different stages after SCI. To inhibit apoptosis, necroptosis, pyroptosis, and ferroptosis after injury and induce autophagy may be the therapeutic strategy. In addition, intervention therapy based on related HUB genes may be the therapeutic target of SCI.

HSPA1A ameliorated spinal cord injury in rats by inhibiting apoptosis to exert neuroprotective effects.

Traumatic spinal cord injury (TSCI) is a serious nervous system insult, and apoptosis in secondary injury is an important barrier to recovery from TSCI. Heat shock protein family A member 1A (HSPA1A) is a protective protein whose expression is elevated after stress. However, whether HSPA1A can inhibit apoptosis after spinal cord injury, and the potential mechanism of this inhibition, remain unclear. In this study, we established in vivo and in vitro models of TSCI and induced HSPA1A overexpression and silencing. HSPA1A upregulation promoted the recovery of neurological function and pathological morphology at the injury site, enhanced neurological cell survival, and inhibited apoptosis in rats following TSCI. In the in vitro model, HSPA1A overexpression inhibited H2O2-induced apoptosis, indicating that HSPA1A suppressed the expression of Bax, caspase-9, and cleaved-caspase-3, promoted the expression of Bcl-2. Furthermore, inhibition of HSPA1A expression can aggravate H2O2-induced apoptosis. We also found that HSPA1A overexpression activated the Wnt/ß-catenin signaling pathway, and that inhibition of this pathway attenuated the inhibitory effect of HSPA1A overexpression on apoptosis. Together, these results indicate that HSPA1A has neuroprotective effects against TSCI that may be exerted through activation of the Wnt/ß-catenin signaling pathway to inhibit apoptosis.

Grape Seed Proanthocyanidins Exert a Neuroprotective Effect by Regulating Microglial M1/M2 Polarisation in Rats with Spinal Cord Injury.

Spinal cord injury (SCI) is a highly disabling disorder for which few effective treatments are available. Grape seed proanthocyanidins (GSPs) are polyphenolic compounds with various biological activities. In our preliminary experiment, GSP promoted functional recovery in rats with SCI, but the mechanism remains unclear. Therefore, we explored the protective effects of GSP on SCI and its possible underlying mechanisms. We found that GSP promoted locomotor recovery, reduced neuronal apoptosis, increased neuronal preservation, and regulated microglial polarisation in vivo. We also performed in vitro studies to verify the effects of GSP on neuronal protection and microglial polarisation and their potential mechanisms. We found that GSP regulated microglial polarisation and inhibited apoptosis in PC12 cells induced by M1-BV2 cells through the Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/AKT) signaling pathways. This suggests that GSP regulates microglial polarisation and prevents neuronal apoptosis, possibly by the TLR4-mediated NF-κB and PI3K/AKT signaling pathways.

N-acetylserotonin protects PC12 cells from hydrogen peroxide induced damage through ROS mediated PI3K / AKT pathway.

N-acetylserotonin (NAS) exerts neuroprotective, antioxidant, and anti-apoptotic effects. Oxidative stress and apoptosis are the primary causes of spinal cord injury (SCI). Herein, we explored potential protective effects and mechanisms of NAS in a neuron oxidative damage model in vitro. We established an oxidative damage model in PC12 cells induced by hydrogen peroxide (H2O2) and treated these cells with NAS. NAS enhanced the activity of superoxide dismutase and halted the increase in reactive oxygen species (ROS) and the expression of inducible nitric oxide synthase. Additionally, NAS promoted protein expression of Bcl-2, but inhibited protein expressions of Fas, FADD, cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, namely, decreasing protein expression of the Fas and mitochondrial pathways. Furthermore, it reduced the rate of apoptosis and necroptosis-related protein expressions of MLKL and p-MLKL. Moreover, NAS promoted the protein expression of p-PI3K and p-AKT, and the addition of the PI3K inhibitor LY294002 partially attenuated the antioxidant stress and anti-apoptotic effects of NAS in H2O2 stimulated PC12 cells. In conclusion, NAS protected PC12 cells from apoptosis and oxidative stress induced by H2O2 by inhibiting ROS activity and activating the PI3K/AKT signaling pathway.

The PI3K/AKT signalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities.

OBJECTS: Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of the spinal cord, which significantly impacts the quality of life in affected patients. The phosphoinositide 3kinase/serine-threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for the inhibition of secondary TSCI. This review summarizes updates concerning the role of the PI3K/AKT pathway in TSCI. MATERIALS AND METHODS: By searching articles related to the TSCI field and the PI3K/AKT signaling pathway, we summarized the mechanisms of secondary TSCI and the PI3K/AKT signaling pathway; we also discuss current and potential future treatment methods for TSCI based on the PI3K/AKT signaling pathway. RESULTS: Early apoptosis and autophagy after TSCI protect the body against injury; a prolonged inflammatory response leads to the accumulation of pro-inflammatory factors and excessive apoptosis, as well as excessive autophagy in the surrounding normal nerve cells, thus aggravating TSCI in the subacute stage of secondary injury. Initial glial scar formation in the subacute phase is a protective mechanism for TSCI, which limits the spread of damage and inflammation. However, mature scar tissue in the chronic phase hinders axon regeneration and prevents the recovery of nerve function. Activation of PI3K/AKT signaling pathway can inhibit the inflammatory response and apoptosis in the subacute phase after secondary TSCI; inhibiting this pathway in the chronic phase can reduce the formation of glial scar. CONCLUSION: The PI3K/AKT signaling pathway has an important role in the recovery of spinal cord function after secondary injury. Inducing the activation of PI3K/AKT signaling pathway in the subacute phase of secondary injury and inhibiting this pathway in the chronic phase may be one of the potential strategies for the treatment of TSCI.

BRD4 Inhibition Suppresses Senescence and Apoptosis of Nucleus Pulposus Cells by Inducing Autophagy during Intervertebral Disc Degeneration: An In Vitro and In Vivo Study.

Intervertebral disc degeneration (IDD) is the most common chronic skeletal muscle degeneration disease. Although the underlying mechanisms remain unclear, nucleus pulposus (NP) autophagy, senescence, and apoptosis are known to play a critical role in this process. Previous studies suggest that bromodomain-containing protein 4 (BRD4) promotes senescent and apoptotic effects in several age-related degenerative diseases. It is not known, however, if BRD4 inhibition is protective in IDD. In this study, we explored whether BRD4 influenced IDD. In human clinical specimens, the BRD4 level was markedly increased with the increasing Pfirrmann grade. At the cellular level, BRD4 inhibition prevented IL-1ß-induced senescence and apoptosis of NP cells and activated autophagy via the AMPK/mTOR/ULK1 signaling pathway. Inhibition of autophagy by 3-methyladenine (3-MA) partially reversed the antisenescence and antiapoptotic effects of BRD4. In vivo, BRD4 inhibition attenuated IDD. Taken together, the results of this study showed that BRD4 inhibition reduced NP cell senescence and apoptosis by induced autophagy, which ultimately alleviated IDD. Therefore, BRD4 may serve as a novel potential therapeutic target for the treatment of IDD.

Therapeutic Effect of Exosomes Derived From Stem Cells in Spinal Cord Injury: A Systematic Review Based on Animal Studies.

Objective: A systematic review of the role of stem cell-derived exosomes in repairing spinal cord injury (SCI) and the existing problems in animal experiments to provide a reference for better animal experiments and clinical studies in the future. Method: Three electronic databases, namely PubMed, Web of Science, and Ovid-Embase were searched. The studies were retrieved from inception to October 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria. Results and Discussion: Thirty-two studies were incorporated into the final analyses. Exosomes derived from stem cells could not only significantly improve the motor function of animals with SCI, but also significantly increase the expression of anti-inflammatory factors IL-4 and IL-10 and anti-apoptotic protein Bcl-2, while significantly lowering the pro-inflammatory factor IL-1ß and TNF-α and the expression of the apoptotic protein BAX. However, the mechanism of exosome-mediated SCI repair, as well as the best source and dosage remain unknown. In addition, there are still some issues with the design, implementation, and reporting of animal experiments in the included studies. Therefore, future research should further standardize the implementation and reporting of animal studies and fully explore the best strategies for exosomes to repair SCI so as to promote the translation of preclinical research results to clinical research better and faster.

Postoperative changes in rib cage deviation in adolescent idiopathic scoliosis.

BACKGROUND: Scoliosis causes changes in the thorax, but it is unclear what type of changes occur in the thoracic profile after scoliosis surgery. OBJECTIVE: To investigate changes in rib cage deviation in the postoperative period after adolescent idiopathic scoliosis (AIS) surgery. METHODS: Forty-four patients with AIS with a main right thoracic curvature underwent posterior surgical fusion (PSF), and radiological parameters of the spine and thorax were evaluated. RESULTS: The correction rates of main thoracic curve (MT)-Cobb angle at immediate after surgery and postoperative follow-up (2 years) were 64% and 66%, respectively. At these two postoperative time points, the correction rates of height of thoracic vertebrae 1 to 12 (T1T12) were 10% and 12%; the correction rates of Rib-vertebra angle difference (RVAD) were 59% and 52%; the correction rates of Apical rib hump prominence (RH) were 58% and 76%; while the correction rates of Apical vertebral body-rib ratio (AVB-R) were 23% and 25%, respectively. Statistical analysis showed that all these radiological parameters at the two postoperative time points were significantly different from the preoperative values (p< 0.001). There were significant correlations between MT-Cobb angle and T1-T12 height (p< 0.001), RVAD (p< 0.001), RH (p< 0.001), and AVB-R (p< 0.001). CONCLUSIONS: Posterior spinal fusion appears to be effective at correcting scoliosis, and the correction of rib cage deviation also plays an important role.

NF-κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a common clinical degenerative disease of the spine. A series of factors, such as inflammation, oxidative stress and mechanical stress, promote degradation of the extracellular matrix (ECM) of the intervertebral discs (IVD), leading to dysfunction and structural destruction of the IVD. Nuclear factor-κB (NF-κB) transcription factor has long been regarded as a pathogenic factor of IDD. Therefore, NF-κB may be an ideal therapeutic target for IDD. As NF-κB is a multifunctional functional transcription factor with roles in a variety of biological processes, a comprehensive understanding of the function and regulatory mechanism of NF-κB in IDD pathology will be useful for the development of targeted therapeutic strategies for IDD, which can prevent the progression of IDD and reduce potential risks. This review discusses the role of the NF-κB signalling pathway in the nucleus pulposus (NP) in the process of IDD to understand pathological NP degeneration further and provide potential therapeutic targets that may interfere with NF-κB signalling for IDD therapy.

Research progress on the regulatory role of microRNAs in spinal cord injury.

Spinal cord injury (SCI) is a severe CNS injury that results in abnormalities in, or loss of, motor, sensory and autonomic nervous function. miRNAs belong to a new class of noncoding RNA that regulates the production of proteins and biological function of cells by silencing translation or interfering with the expression of target mRNAs. Following SCI, miRNAs related to oxidative stress, inflammation, autophagy, apoptosis and many other secondary injuries are differentially expressed, and these miRNAs play an important role in the progression of secondary injuries after SCI. The purpose of this review is to elucidate the differential expression and functional roles of miRNAs after SCI, thus providing references for further research on miRNAs in SCI.

Different Types of Double-Level Degenerative Lumber Spondylolisthesis: What Is Different in the Sagittal Plane?

BACKGROUND: Degenerative lumber spondylolisthesis (DLS) is a common orthopedic condition, described as a condition that compared with the lower vertebra, the superior vertebra slides forward or backward in the sagittal plane without accompanying isthmic spondylolisthesis. Information pertaining to different types of double-level DLS is scarce. This study aims to analyze parameters of patients with different types of double-level DLS to provide a reference for guiding surgical treatment and restoring sagittal balance of patients with DLS. METHODS: From January 2014 to January 2020, records of patients with double-level DLS were retrospectively reviewed. Patients with double-level DLS were divided into 3 types: anterior, posterior, and combined; the anterior and combined types were studied. The sagittal spinopelvic parameters included C7 tilt, maximal thoracic kyphosis, maximal lumbar lordosis (LLmax), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). After descriptive analysis, demographic and radiographic data were compared. RESULTS: Forty and 18 patients were included in the anterior and combined type groups, respectively. Both groups had different levels of chronic low back pain, but the incidence of radiating leg pain and neurogenic claudication was significantly higher in the anterior type. Oswestry Disability Index and visual analog scale low back scores were also higher in the anterior type. In the anterior type, C7 tilt (7.14 ± 2.15 vs. 5.41 ± 2.28, P = 0.007), LLmax (50.02 ± 14.76 vs. 36.96 ± 14.56, P = 0.003), PI (68.28 ± 9.16 vs. 55.53 ± 14.19, P < 0.001), PT (28.68 ± 7.31 vs. 19.38 ± 4.70, P < 0.001), and PT/PI (42.45 ± 11.22 vs. 36.04 ± 9.87, P = 0.041) were significantly higher. In the anterior type, PI correlated positively with LLmax (r = 0.59) and SS (r = 0.71). LLmax and SS (r = 0.65) had a positive correlation. PT/PI and SS (r = -0.77) had a negative correlation. In the combined type, PI correlated positively with LLmax (r = 0.61) and SS (r = 0.88), and PT/PI correlated negatively with SS (r = -0.81). CONCLUSIONS: In patients with double-level DLS, the sagittal spinopelvic parameters differed between the anterior and combined types. Overall, spinal surgeons should focus on correcting sagittal deformities, relieving postoperative clinical symptoms, and improving quality of life during fusion surgery.

Grape seed proanthocyanidins protect PC12 cells from hydrogen peroxide-induced damage via the PI3K/AKT signaling pathway.

Grape seed proanthocyanidins (GSP) are natural flavonoids with strong antioxidant and anti-apoptotic effects. Oxidative stress and neuronal apoptosis are major contributors to spinal cord injury (SCI). In this study, we assessed the potential protective effects of GSP on hydrogen peroxide (H2O2)-damaged pheochromocytoma-12 (PC12) cells in an in vitro model of SCI as well as the putative mechanism of action. We established a model using PC12 cells with oxidative damage induced by H2O2. Cells were treated with various concentrations of GSP (control group, 200 µmol/L H2O2 group, 5 µM GSP + H2O2 group, 10 µM GSP + H2O2 group, and 25 µM GSP + H2O2 group). The CCK-8 assay was used to determine cell activity. Dichloro-dihydro-fluorescein diacetate was used to detect intracellular reactive oxygen species (ROS), and flow cytometry was used to determine apoptosis rate. Western blot analysis was used to detect the expression of caspase-3, Bax, Bcl-2, and PI3K/AKT proteins. The results showed that GSP reduced H2O2-induced intracellular ROS and inhibited apoptosis. Furthermore, GSP inhibited the expression of caspase-3 and Bax, while promoting the expression of Bcl-2. In addition, GSP promoted the phosphorylation of PI3K and AKT. Moreover, a PI3K inhibitor (LY294002) weakened the protective effects of GSP on H2O2-induced PC12 cells. In conclusion, GSP pretreatment can protect PC12 cells from oxidative damage induced by H2O2 via the PI3K/AKT signaling pathway.

Single-segment central lumbar spinal stenosis: Correlation with lumbar X-ray measurements.

BACKGROUND: Lumbar X-rays are usually preferred in patients with lower back pain, but lumbar spinal stenosis (LSS) cannot be directly observed on lumbar X-ray films. OBJECTIVE: The purpose of this study is to explore the correlation between the degree of single-segment central LSS and lumbar X-ray measurements. METHODS: The data of 60 male patients aged 39-78 years with single-segment central LSS were analyzed. Linear correlation analysis was used to determine the correlation between the single-segment central LSS and the various measurement parameters. Multiple linear regression analysis was used to analyze the factors affecting single-segment central LSS. RESULTS: There were significant differences in S1/S0, E, B, L1-5Cobb, and M among the three groups (p< 0.05). S1/S0 was positively correlated with E, B, L1-5Cobb, and M (p< 0.05), but was not correlated with D (p= 0.66). After multiple linear regression analysis, B, L1-5Cobb, and M were independently associated with S1/S0. CONCLUSIONS: The B, L1-5Cobb, and M parameters were independently associated with single-stage central LSS, and would likely be of particular value in evaluating the degree of single-segment central LSS; B, L1-5Cobb, and M served as independent predictors of the degree of LSS. These findings will guide clinicians' decision-making in the future.