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BACKGROUND: Despite the important clinical issue of cognitive impairment after moderate traumatic brain injury (TBI), there is currently no suitable treatment. Here, we used in vitro and in vivo models to investigate the effect of Donepezil-an acetylcholinesterase (AChE) inhibitor-on cognitive impairment in the acute period following injury, while focusing on neuroinflammation and autophagy- and mitophagy-related markers. METHODS: The purpose of the in vitro study was to investigate potential neuroprotective effects in TBI-induced cells after donepezil treatment, and the in vivo study, the purpose was to investigate therapeutic effects on cognitive impairment in the acute period after injury by analyzing neuroinflammation and autophagy- and mitophagy-related markers. The in vitro TBI model involved injuring SH-SY5Y cells using a cell-injury controller and then investigating the effect of donepezil at a concentration of 80 µM. The in vivo TBI model was made using a stereotaxic impactor for male C57BL/6J mice. Immuno-histochemical markers and cognitive functions were compared after 7 days of donepezil treatment (1 mg/kg/day). Mice were divided into four groups: sham operation with saline treatment, sham operation with donepezil treatment, TBI with saline treatment, and TBI with donepezil treatment (18 mice in each group). Donepezil treatment was administered within 4 h post-TBI. RESULTS: In vitro, donepezil was found to lead to increased cell viability and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), along with decreased reactive oxygen species (ROS), lactate-dehydrogenase (LDH), 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA)-positive cells, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. The mRNA and protein expressions of neuroinflammation (Cyclooxygenase-2, COX-2; NOD-like receptor protein 3, NLRP3; Caspase-1; and Interleukin-1 beta, IL-1ß), as well as autophagy- and mitophagy-related markers (death-associated protein kinase 1, DAPK1; PTEN-induced kinase 1, PINK1; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like, BNIP3L; Beclin-1, BECN1; BCL2-associated X protein, BAX; microtubule-associated protein 1A/1B-light chain 3B (LC3B); Sequestosome-1; and p62) were all found to decrease after donepezil treatment. The in vivo study also showed that donepezil treatment resulted in decreased levels of cortical tissue losses and brain swelling in TBI compared to the TBI group without donepezil treatment. Donepezil treatment was also shown to decrease the mRNA and Western blotting expressions of all markers, and especially COX-2 and BNIP3L, which showed the most significant decreases. Moreover, TBI mice showed an decreased escape latency, increased alteration rate, and improved preference index, altogether pointing to better cognitive performance after donepezil treatment. CONCLUSIONS: Donepezil treatment may be beneficial in improving cognitive impairment in the early phase of moderate traumatic brain injury by ameliorating neuroinflammation, as well as autophagy and mitophagy.
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Clinical outcome after traumatic brain injury (TBI) is closely associated conditions of other organs, especially lungs as well as degree of brain injury. Even if there is no direct lung damage, severe brain injury can enhance sympathetic tones on blood vessels and vascular resistance, resulting in neurogenic pulmonary edema. Conversely, lung damage can worsen brain damage by dysregulating immunity. These findings suggest the importance of brain-lung axis interactions in TBI. However, little research has been conducted on the topic. An advanced disease model using stem cell technology may be an alternative for investigating the brain and lungs simultaneously but separately, as they can be potential candidates for improving the clinical outcomes of TBI.In this review, we describe the importance of brain-lung axis interactions in TBI by focusing on the concepts and reproducibility of brain and lung organoids in vitro. We also summarize recent research using pluripotent stem cell-derived brain organoids and their preclinical applications in various brain disease conditions and explore how they mimic the brain-lung axis. Reviewing the current status and discussing the limitations and potential perspectives in organoid research may offer a better understanding of pathophysiological interactions between the brain and lung after TBI.
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OBJECTIVE: Both the Global Alignment and Proportion (GAP) score and Roussouly classification account for the lordosis distribution index (LDI), but the LDI of the GAP score (G-LDI) is typically set to 50%-80%, while the LDI of the Roussouly classification (R-LDI) varies depending on the degree of pelvic incidence (PI). The objective of this study was to validate the ability of the G-LDI to predict mechanical complications and compare it with the predictive probability of R-LDI in patients with long-level fusion surgery. METHODS: A total of 171 patients were divided into two groups: 93 in the nonmechanical complication group (non-MC group) and 78 in the mechanical complication group (MC group). The mean age of the participants was 66.79 ± 8.56 years (range 34-83 years), and the mean follow-up period was 45.49 ± 16.20 months (range 24-62 months). The inclusion criteria for the study were patients who underwent > 4 levels of fusion and had > 2 years of follow-up. The predictive models for mechanical complications using the G-LDI and R-LDI were analyzed using binomial logistic regression and receiver operating characteristic analyses. RESULTS: There was a significant correlation between R-LDI and PI (r = -0.561, p < 0.001), while there was no correlation between G-LDI and PI (r = 0.132, p = 0.495). In reference to G-LDI, most patients in the non-MC group were classified as having alignment (72, 77.4%), while the MC group had an inhomogeneous composition (aligned: 34, 43.6%; hyperlordosis: 37, 47.4%). The agreement between the G-LDI and R-LDI was moderate (κ = 0.536, p < 0.001) to fair (κ = 0.383, p = 0.011) for patients with average or large PI, but poor (κ = -0.255, p = 0.245) for those with small PI. The areas under the curve for the G-LDI and R-LDI were 0.674 (95% CI, 0.592-0.757) and 0.745 (95% CI, 0.671-0.820), respectively. CONCLUSIONS: The R-LDI, which uses a PI-based proportional parameter, enables individual quantification of LL for all PI sizes and has been shown to have a higher accuracy in classifying cases and a stronger correlation with the risk of mechanical complications compared with G-LDI.
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Lordosis , Postoperative Complications , Spinal Fusion , Humans , Middle Aged , Aged , Female , Male , Spinal Fusion/adverse effects , Spinal Fusion/methods , Adult , Lordosis/surgery , Lordosis/diagnostic imaging , Aged, 80 and over , Postoperative Complications/classification , Lumbar Vertebrae/surgery , Retrospective Studies , Predictive Value of Tests , Follow-Up StudiesABSTRACT
Thoracic ossification of the ligamentum flavum (TOLF) is a rare pathology for which limited research exists. While it is known that mechanical factors play a role in the development of TOLF, little is currently understood about the sagittal alignment and related mechanical stress involved in its development. This study aims to describe the sagittal alignment of patients with TOLF based on the pathologic evolution of the Roussouly classification. The current study evaluated the preoperative Roussouly type in consecutive patients who underwent posterior decompressive laminectomy with or without posterior screw fixation for TOLF between January 2015 and December 2021. The post-evolution sagittal alignments were analyzed using the classic Roussouly classification based on sacral slope (SS). To determine the pre-evolution Roussouly type, the patients were retrospectively classified using their individual PI and PT values. Lumbopelvic parameters and morphological index including inflection point (IP), lumbar apex (LA), and lordosis distribution index (LDI) were also evaluated. Forty-three patients (21 women and 22 men) were included; their mean age was 64.21â ±â 11.01 years (range 43-81). The most affected level was T10-11 (48.83%). The mean PI was 50.81â ±â 9.56°, the mean SS was 33.11â ±â 8.61°and the mean PT was 17.69â ±â 7.89°. According to the post-evolution Roussouly classification, type 2 shape was the most frequently observed type (nâ =â 23, 53.5%) in the post-evolution classification while type 3 was the most common type observed in the pre-evolution classification (nâ =â 22, 51.5% and Pâ =â .00). The level of IP and LA in type 3 moved caudally (around L2 and L4/5 level, respectively) and the LDI increased (77.98â ±â 8.08%) than the normal standard value. The authors found that the majority of the patients had a false type 2 spine, which had evolved pathologically from Roussouly type 3 and exhibited increased LDI, a lowered level of IP, and a lowered level of LA. These changes of spinal shape, including the transition to long hypolordosis and increased length of the thoracic kyphosis, may have accentuated tensile stress at the lower thoracic spine and contributed to the development of TOLF.
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Kyphosis , Ligamentum Flavum , Lordosis , Male , Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Retrospective Studies , Ligamentum Flavum/surgery , Osteogenesis , Lordosis/pathology , Kyphosis/etiology , Kyphosis/surgery , Sacrum , Thoracic Vertebrae/surgery , Thoracic Vertebrae/pathology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgeryABSTRACT
We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2-ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p < 0.01). We observed the association between increased mitochondrial dysfunction concomitant with autophagy and mitophagy in CSF cells and neurological outcomes in adult patients with hemorrhagic MMD. Further prospective multicenter studies are needed to determine whether it has a diagnostic value for risk prediction.
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Mitophagy , Moyamoya Disease , Adult , Female , Humans , Middle Aged , Antibodies , Autophagy , bcl-2-Associated X Protein , Mitochondria , MaleABSTRACT
OBJECTIVE: There are no effective clinically applicable treatments for neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated the therapeutic effect of a new delivery method of mouse neural stem cell (mNSC) spheroids using a hydrogel, in terms of improvement in damaged cortical lesions and cognitive impairment after mild TBI. METHODS: mNSCs were isolated from the subventricular zone and subgranular zone by a hydrogel-based culture system. GFP-transduced mNSCs were generated into spheroids and wrapped into a sheet for transplantation. Male C57BL/6J mice were randomly divided into four groups: sham operation, TBI, TBI with mNSC spheroids, and TBI with mNSC spheroid sheet transplantation covering the damaged cortex. Histopathological and immunohistochemical features and cognitive function were evaluated 7, 14, and 28 days after transplantation following TBI. RESULTS: Hydrogel-based culture systems and mNSC isolation were successfully established from the adult mice. Essential transcription factors for NSCs, such as SOX2, PAX6, Olig2, nestin, and doublecortin (DCX), were highly expressed in the mNSCs. A transplanted hydrogel-based mNSC spheroid sheet showed good engraftment and survival ability, differentiated into TUJ1-positive neurons, promoted angiogenesis, and reduced neuronal degeneration. Also, TBI mice treated with mNSC spheroid sheet transplantation exhibited a significantly increased preference for a new object, suggesting improved cognitive function compared to the mNSC spheroids or no treatment groups. CONCLUSION: Transplantation with a hydrogel-based mNSC spheroid sheet showed engraftment, migration, and stability of delivered cells in a hostile microenvironment after TBI, resulting in improved cognitive function via reconstruction of the damaged cortex. STATEMENT OF SIGNIFICANCE: This study presents the therapeutic effect of a new delivery method of mouse neural stem cells spheroids using a hydrogel, in terms of improvement in damaged cortical lesions and cognitive impairment after traumatic brain injury. Collagen/fibrin hydrogel allowed long-term survival and migratory ability of NSCs spheroids. Furthermore, transplanted hydrogel-based mNSCs spheroids sheet showed good engraftment, migration, and stability of delivered cells in a hostile microenvironment, resulting in reconstruction of the damaged cortex and improved cognitive function after TBI. Therefore, we suggest that a hydrogel-based mNSCs spheroids sheet could help to improve cognitive impairment after TBI.
Subject(s)
Brain Concussion , Brain Injuries, Traumatic , Neural Stem Cells , Male , Mice , Animals , Brain Concussion/pathology , Hydrogels/pharmacology , Mice, Inbred C57BL , Neurons , Brain Injuries, Traumatic/pathologyABSTRACT
BACKGROUND: We aimed to investigate the effects of oxiracetam on cognitive impairment in the early phase of traumatic brain injury (TBI), for which no specific treatment is currently available. METHODS: The in vitro study used a cell injury controller to damage SH-SY5Y cells and evaluate the effect of oxiracetam at a dosage of 100 nM. The in vivo study used a stereotaxic impactor to induce a TBI model in C57BL/6 J mice and analyzed immunohistochemical changes and cognitive function after an intraperitoneal injection of oxiracetam (30 mg/kg/day) for 5 days. The number of mice used in this study was 60. They were divided into three groups (sham, TBI, and TBI with oxiracetam treatment) (20 mice in each group). RESULTS: The in vitro study showed that oxiracetam treatment resulted in increased superoxide dismutase (SOD)1 and SOD2 mRNA expression. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and interleukin (IL)-1 ß were decreased after oxiracetam treatment, along with decreases in intracellular reactive oxygen species production and apoptotic effects. TBI mice treated with oxiracetam exhibited the loss of fewer cortical damaged lesions, less brain edema, and fewer Fluoro-Jade B (FJB)-positive and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-positive cells compared to those without oxiracetam treatment. The mRNA and protein expression of COX-2, NLRP3, caspase-1, and IL-1ß were decreased significantly after oxiracetam treatment. These inflammation-related markers, which colocalized with Iba-1-positive or GFAP-positive cells after TBI, were also decreased after oxiracetam treatment. TBI mice treated with oxiracetam had a smaller decrease in preference and more latency time than those not treated with oxiracetam, suggesting the amelioration of impaired cognitive impairment. CONCLUSIONS: Oxiracetam may be helpful in restoring cognitive impairment by ameliorating neuroinflammation in the early phase of TBI.
Subject(s)
Brain Injuries, Traumatic , Cognitive Dysfunction , Neuroblastoma , Rats , Mice , Humans , Animals , NLR Family, Pyrin Domain-Containing 3 Protein , Rats, Sprague-Dawley , Cyclooxygenase 2 , Mice, Inbred C57BL , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/metabolism , Anti-Inflammatory Agents/therapeutic use , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Messenger/therapeutic use , Caspases/therapeutic use , Disease Models, AnimalABSTRACT
OBJECTIVE: We performed an expanded multi-ethnic meta-analysis to identify associations between inflammation-related loci with intracranial aneurysm (IA) susceptibility. This meta-analysis possesses increased statistical power as it is based on the most data ever evaluated. METHODS: We searched and reviewed relevant literature through electronic search engines up to August 2022. Overall estimates were calculated under the fixed- or random-effect models using pooled odds ratio (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed according to ethnicity. RESULTS: Our meta-analysis enrolled 15 studies and involved 3070 patients and 5528 controls including European, Asian, Hispanic, and mixed ethnic populations. Of 17 inflammation-related variants, the rs1800796 locus (interleukin [IL]-6) showed the most significant genome-wide association with IA in East-Asian populations, including 1276 IA patients and 1322 controls (OR, 0.65; 95% CI, 0.56-0.75; p=3.24×10-9) under a fixed-effect model. However, this association was not observed in the European population (OR, 1.09; 95% CI, 0.80-1.47; p=0.5929). Three other variants, rs16944 (IL-1ß), rs2195940 (IL-12B), and rs1800629 (tumor necrosis factor-α) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01
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Ahead of Print article withdrawn by publisher.
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Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.
Subject(s)
Longitudinal Ligaments , Ossification of Posterior Longitudinal Ligament , Humans , Longitudinal Ligaments/metabolism , Longitudinal Ligaments/pathology , Osteogenesis/genetics , Ossification of Posterior Longitudinal Ligament/genetics , Ossification of Posterior Longitudinal Ligament/pathology , Reactive Oxygen Species/metabolism , Ferritins/genetics , Ferritins/metabolismABSTRACT
Kallikrein-related peptidase (KLK)6 is associated with inflammatory diseases and neoplastic progression. KLK6 is aberrantly expressed in several solid tumors and regulates cancer development, metastatic progression, and drug resistance. However, the function of KLK6 in the tumor microenvironment remains unclear. This study aimed to determine the role of KLK6 in the tumor microenvironment. Here, we uncovered the mechanism underlying KLK6-mediated cross-talk between cancer cells and macrophages. Compared with wild-type mice, KLK6-/- mice showed less tumor growth and metastasis in the B16F10 melanoma and Lewis lung carcinoma (LLC) xenograft model. Mechanistically, KLK6 promoted the secretion of tumor necrosis factor-alpha (TNF-α) from macrophages via the activation of protease-activated receptor-1 (PAR1) in an autocrine manner. TNF-α secreted from macrophages induced the release of the C-X-C motif chemokine ligand 1 (CXCL1) from melanoma and lung carcinoma cells in a paracrine manner. The introduction of recombinant KLK6 protein in KLK6-/- mice rescued the production of TNF-α and CXCL1, tumor growth, and metastasis. Inhibition of PAR1 activity suppressed these malignant phenotypes rescued by rKLK6 in vitro and in vivo. Our findings suggest that KLK6 functions as an important molecular link between macrophages and cancer cells during malignant progression, thereby providing opportunities for therapeutic intervention.
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Kallikreins , Melanoma , Receptor, PAR-1 , Animals , Mice , Kallikreins/metabolism , Macrophages/metabolism , Receptor, PAR-1/metabolism , Tumor Microenvironment , Tumor Necrosis Factor-alphaABSTRACT
OBJECTIVE: There are no effective treatments for relieving neuronal dysfunction after mild traumatic brain injury (TBI). Here, we evaluated therapeutic efficacy of human embryonic stem cell-derived cerebral organoids (hCOs) in a mild TBI model, in terms of repair of damaged cortical regions, neurogenesis, and improved cognitive function. METHODS: Male C57BL/6 J mice were randomly divided into sham-operated, mild TBI, and mild TBI with hCO groups. hCOs cultured at 8 weeks were used for transplantation. Mice were sacrificed at 7 and 14 days after transplantation followed by immunofluorescence staining, cytokine profile microarray, and novel object recognition test. RESULTS: 8W-hCOs transplantation significantly reduced neuronal cell death, recovered microvessel density, and promoted neurogenesis in the ipsilateral subventricular zone and dentate gyrus of hippocampus after mild TBI. In addition, increased angiogenesis into the engrafted hCOs was observed. Microarray results of hCOs revealed neuronal differentiation potential and higher expression of early brain development proteins associated with neurogenesis, angiogenesis and extracellular matrix remodeling. Ultimately, 8W-hCO transplantation resulted in reconstruction of damaged cortex and improvement in cognitive function after mild TBI. CONCLUSION: hCO transplantation may be feasible for treating mild TBI-related neuronal dysfunction via reconstruction of damaged cortex and neurogenesis in the hippocampus.
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Brain Concussion , Brain Injuries, Traumatic , Human Embryonic Stem Cells , Animals , Humans , Male , Mice , Brain Concussion/complications , Brain Injuries, Traumatic/drug therapy , Disease Models, Animal , Mice, Inbred C57BL , Neurogenesis/physiology , OrganoidsABSTRACT
Retrospective cross-sectional study To evaluate the validity and obtain optimal cutoff values of 3 radiologic measurements for the diagnosis of basilar invagination (BI). Two hundred seventy-six patients (46 patients who underwent atlantoaxial fusion for BI and 230 patients who were treated for minor cervical trauma) seen in a single institution from January 2010 to December 2016 were included in this study. Age, sex, and body mass index were adjusted for the patients. The Ranawat index (RI), modified Ranawat method (MRM), and Redlund-Johnell method (RJM) were used to diagnose BI on plain radiographs. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and diagnostic odds ratio of 3 radiologic measurements were compared. We also calculated the optimized cutoff values of 3 radiologic measurements using the receiver operating characteristic curve in our patients. The mean age of the 130 women and 146 men was 58.3â ±â 14.5 years. The mean values of RI, MRM, and RJM in the BI group were 12.5â ±â 3.3, 23.1â ±â 3.8, and 27.3â ±â 3.6 in women and 13.6â ±â 2.6, 26.8â ±â 4.2, and 34.7â ±â 5.1 in men. There was a significant difference between the sexes (Pâ <â .05). The accuracies of RI, MRM, and RJM were 95%, 89.6%, and 92.3% in women and 93%, 68.2%, and 85.4% in men, respectively. The optimized cutoff values of RI, MRM, and RJM were 14, 26, and 32 mm in women and 15, 29, and 38 mm in men. Three radiologic measurements (RI, MRM, and RJM) are reliable for the diagnosis of BI even in the era of cross-sectional images. The validity of these measurements depends on sex and particular radiologic measurement. The optimized cutoff values of RI, MRM, and RJM were 14, 26, and 32 mm in women and 15, 29, and 37 mm in men. These cutoff values showed high validity when compared to the CT and MRI findings.
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Atlanto-Axial Joint , Platybasia , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Platybasia/diagnostic imaging , Radiography , Retrospective StudiesABSTRACT
Recently, with the growing interest in indoor location-based services, visible light positioning (VLP) systems have been extensively studied owing to their advantages of low cost, high energy efficiency, and no electromagnetic interference. However, due to structural limitations which lead to the requirement of multiple signal sources, it has been challenging to apply VLP in real-world scenarios. In this study, we propose a single LED, single PD-based tracking system that solves these problems by applying a new Bayesian method that can effectively reduce the computational burden of particle filters. The method of evaluating particle reliability developed in this work adjusts the number of particles on the fly. Using the absolute position of the single LED source, the long-term cumulative error of the inertial measurement unit can be continuously corrected. In this regard, the applicability of the VLP system can be enhanced in places where the multiple luminescent signals are hard to consistently detect. The proposed system was verified through experiments in a classroom and a corridor, and the results show an average error of less than 11 cm at travel distances of 80 to 100 m.
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BACKGROUND: The goal of the present study was to investigate the impact of C3 involvement on the postoperative kyphosis following cervical laminoplasty in patients with high and low T1S. METHODS: The data from ossification of the posterior longitudinal ligament patients who had undergone laminoplasty between January 2016 and December 2019 were retrospectively reviewed. Patients were divided into low-and high-T1S groups according to preoperative T1S, and the postoperative alignment change was compared between the groups. The relationships between postoperative cervical kyphosis and preoperative variables, including gender, C3 laminoplasty, T1S, cervical lordosis (CL), C2-7 Sagittal Vertical Axis, and T1S minus CL (T1S-CL) were investigated. RESULTS: Eighty-six patients were divided into 2 groups above and below median preoperative T1S (23.70). There were thirty-three patients (38.3%) in low-T1S group and fifty-three patients (61.7%) in high-T1S group. Twenty-three patients (26.7%) were performed with C3 involved laminoplasty. C3 laminoplasty (odds ratio [OR], 9.67; 2.82-33.16; P = 0.000), high T1S (OR, 4.89; 1.54-15.49; P = 0.007), and mismatched T1S-CL (OR, 5.96; 1.83-19.43; P = 0.003) were significantly associated with postoperative kyphosis. In high-T1S group, the loss of CL was significant (P = 0.017) when C3 laminoplasty was performed, whereas, in low-T1S group, the C3 laminoplasty did not show the statistically significant difference. (P = 0.194). CONCLUSIONS: C3 laminoplasty, mismatched T1S-CL, and high T1S were found to increase the risk of postoperative kyphosis following cervical laminoplasty. Patients with high T1 slope tended to exhibit a greater loss of CL when the laminoplasty was performed extending to C3 segment.
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Kyphosis , Laminoplasty , Lordosis , Humans , Laminoplasty/adverse effects , Retrospective Studies , Cervical Vertebrae/surgery , Kyphosis/etiology , Kyphosis/surgery , Lordosis/surgeryABSTRACT
BACKGROUND/AIM: Dark tea, made by fermentation of tea leaves using microorganisms, is well known for its antiobesity effect; however, studies to identify this effect have not been sufficiently conducted. Herein, the anti-obesity effects of post-fermented dark tea were studied in high-fat diet mouse. MATERIALS AND METHODS: Obesity was induced through a high-fat diet in C57BL/6 mice, and then dark tea extract powder (DTP) was orally administered daily for 12 weeks to evaluate the body and organ weights. Changes in the biochemical markers of obesity were evaluated to study the mechanism of the anti-obesity effects of DTP. RESULTS: When DTP was administered to obesity mice, the weight and food intake reduced, blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) decreased, whereas high-density lipoprotein cholesterol (HDL-C) increased. Histopathology showed that steatosis and inflammation scores were reduced within the liver and adipocyte sizes were reduced within epididymal adipocyte. In addition, a significant decrease in blood insulin and hepatic TG and a significant increase in blood adiponectin were also confirmed. The results of western blot and qPCR in week 12, showed a significant decrease in the mRNA and protein levels of C/EBPα, and the mRNA levels of PPARγ in the liver. CONCLUSION: Dark tea extracts are thought to have an anti-obesity effect by reducing the levels of the main transcription factors that promote adipocyte differentiation, such as C/EBPα, and PPARγ. Therefore, diet products using dark tea extracts could be developed.
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CCAAT-Enhancer-Binding Protein-alpha , PPAR gamma , Animals , CCAAT-Enhancer-Binding Protein-alpha/genetics , CCAAT-Enhancer-Binding Protein-alpha/metabolism , CCAAT-Enhancer-Binding Protein-alpha/pharmacology , Cholesterol , Diet, High-Fat/adverse effects , Down-Regulation , Liver/pathology , Mice , Mice, Inbred C57BL , Obesity/metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , RNA, Messenger/metabolism , Tea/chemistry , Triglycerides/metabolism , Triglycerides/pharmacologyABSTRACT
OBJECTIVE: To evaluate which radiologic parameters affect clinical outcomes in patients underwent posterior C1-2 fusion for atlantoaxial dislocation. METHODS: From January 2014 to December 2017, among 98 patients underwent C1-2 posterior fusion, patients with previous cervical surgery or extending to subaxial spine or basilar invagination were excluded. Finally, 38 patients were included. O-C2, C1-2, C1-C7, C2-C7 cobb angle (CA), T1 slope, C1-7, C2-7 sagittal vertical axis (SVA), and posterior atlantodental interval (PADI) were measured at preoperative and postoperative 1 year. The difference between postoperative and preoperative values for each parameter was designated as Δvalue. Postoperative subaxial kyphosis (PSK) was defined to decrease ≥ 10° at subaxial spine. Visual analogue scale (VAS), Japanese Orthopedic Association (JOA) score, Neck Disability Index (NDI) were used to evaluate clinical outcomes. RESULTS: Mean age was 54.4 ± 15.9. Male to female was 14 to 24. Of radiologic parameters, C1-7 SVA and PADI were significantly changed from 26.4 ± 12.9 mm, 17.1 ± 3.3 mm to 22.6 ± 13.0 mm, 21.6 ± 3.4 mm. ΔC1-2 CA was correlated with ΔC1-7 CA and ΔC2-7 SVA. ΔPADI correlates with ΔO-C2 CA. VAS correlates with ΔC1-7 CA (p = 0.03). JOA score also correlates with ΔC2-7 SVA (p = 0.02). NDI was associated with ΔPADI (p < 0.01). The incidence of PSK was 23.7%, and not significant with clinical outcomes. CONCLUSION: ΔC1-2 CA was correlated with ΔC1C7 CA, ΔC2-7 SVA. ΔC1-7 CA, ΔC2-7 SVA, and ΔPADI were the key radiologic parameters to influence clinical outcomes. Postoperative C1-2 angle should be carefully determined as a factor affecting clinical outcomes and cervical sagittal alignment.
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Although technological advances and clinical studies on stem cells have been increasingly reported in stroke, research targeting hemorrhagic stroke is still lacking compared to that targeting ischemic stroke. Studies on hemorrhagic stroke are also being conducted, mainly in the USA and China. However, little research has been conducted in Korea. In reality, stem cell research or treatment is unfamiliar to many domestic neurosurgeons. Nevertheless, given the increased interest in regenerative medicine and the increase of life expectancy, attention should be paid to this topic. In this paper, we summarized pre-clinical rodent studies and clinical trials using stem cells for hemorrhagic stroke. In addition, we discussed results of domestic investigations and future perspectives on stem cell research for a better understanding.
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Recent trends suggest novel natural compounds as promising treatments for cardiovascular disease. The authors examined how neopetroside A, a natural pyridine nucleoside containing an α-glycoside bond, regulates mitochondrial metabolism and heart function and investigated its cardioprotective role against ischemia/reperfusion injury. Neopetroside A treatment maintained cardiac hemodynamic status and mitochondrial respiration capacity and significantly prevented cardiac fibrosis in murine models. These effects can be attributed to preserved cellular and mitochondrial function caused by the inhibition of glycogen synthase kinase-3 beta, which regulates the ratio of nicotinamide adenine dinucleotide to nicotinamide adenine dinucleotide, reduced, through activation of the nuclear factor erythroid 2-related factor 2/NAD(P)H quinone oxidoreductase 1 axis in a phosphorylation-independent manner.
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Barley sprouts are known to have several effective physiological activities. In this study, the anti-obesity effect of a barley sprout hot water extract (BSE) was confirmed. Saponarin was quantitatively analyzed in BSE using HPLC, and the inhibitory effect on 3T3-L1 pre-adipocyte differentiation into adipocytes was confirmed by Oil Red O staining, TG assay, and Western blotting. In addition, the inhibitory effect of BSE on adipocyte growth was confirmed through glucose uptake and lipolysis of adipocytes. C57/BL/6N mice were induced to obesity with a high-fat diet, and BSE was administered to confirm the effect on an animal model. Weight gain, morphological changes in adipose tissue, changes in the food efficiency ratio, and blood biochemical changes were observed, and an improvement effect on fatty liver was confirmed. As a result, the anti-obesity effect of BSE was confirmed in vitro, and it was confirmed that this effect was also effective in vivo and that it could be helpful in the treatment of obesity-related diseases.