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Abstract 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.

Paulownin, a natural compound derived from Paulownia tomentosa wood, exhibits various physiological functions, including anti-bacterial and anti-fungal effects. However, the impact of paulownin on natural killer (NK) cell immune activity remains largely unknown. In this study, we investigated the effect of paulownin on NK cell activity both in vitro and in vivo, and explored its potential mechanisms. NK-92 cells were used for in vitro experiments and a BALB/c mouse model with B16F10 cells injected subcutaneously were used for in vivo anti-tumor analysis. We found that paulownin enhanced the cytolytic activity of NK-92 cells against leukemia, human colon, and human lung cancer cell lines. Paulownin treatment increased the expression of the degranulation marker protein CD107a and cytolytic granules, including granzyme B and perforin in NK-92 cells. Moreover, these enhancements of cytotoxicity and the expression of cytolytic granules induced by paulownin were also observed in human primary NK cells. Signaling studies showed that paulownin promoted the phosphorylation of JNK. The increased perforin expression and elevated cytotoxic activity induced by paulownin were effectively inhibited by pre-treatment with a JNK inhibitor. In vivo studies demonstrated that the administration of paulownin suppressed the growth of B16F10 melanoma cells allografted into mice. Paulownin administration promoted the activation of NK cells in the spleen of mice, resulting in enhanced cytotoxicity against YAC-1 cells. Moreover, the anti-tumor effects of paulownin were reduced upon the depletion of NK cells. Therefore, these results suggest that paulownin enhances NK cell cytotoxicity by activating the JNK signaling pathway and provide significant implications for developing new strategies for cancer immunotherapy.

Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays a critical role in regulating the activity of Rho guanosine triphosphatases (GTPases). Phosphorylation of RhoGDI1 dynamically modulates the activation of Rho GTPases, influencing cell proliferation and migration. This study explored the involvement of Never In Mitosis A (NIMA)-related serine/threonine protein kinase 2 (NEK2) in phosphorylating RhoGDI1 and its implications in cancer cell behavior associated with tumor progression. We employed GST pull-down assays and immunoprecipitation to investigate the interaction between NEK2 and RhoGDI1. Truncation fragments identified the region of RhoGDI1 responsible for binding with NEK2. Phosphorylation assays determined the site of NEK2-mediated phosphorylation on RhoGDI1. Functional assays were conducted using overexpression of the RhoGDI1 substitution mutant to assess their impact on cancer cell behavior. NEK2 directly bound to RhoGDI1 and phosphorylated it at Ser174. This phosphorylation event facilitated cancer cell proliferation and motility by activating RhoA and Rac1. The RhoGDI1 aa 112–134 region was critical for the binding to NEK2. Disruption of the NEK2–RhoGDI1 interaction through overexpression of a RhoGDI1 truncated fragment (aa 112–134) led to diminished RhoGDI1 phosphorylation and RhoA/Rac1 activation induced by NEK2, resulting in reduced cancer cell proliferation and migration. Moreover, in vivo studies showed reduced tumor growth and lung metastasis when the NEK2–RhoGDI1 interaction was disrupted. This study indicates that NEK2 promotes the metastatic behaviors of cancer cells by activating RhoA and Rac1 by phosphorylating RhoGDI1.

Abstract 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

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-1β), 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.

Objective To evaluate a radiological difference between the oblique lumbar interbody fusion (OLIF) L5-S1 and transforaminal lumbar interbody fusion (TLIF) L5-S1 procedure. Methods 16 patients who underwent single-level OLIF L5-S1 and 32 patients of TLIF L5-S1 were retrospectively reviewed. Assessment of the lumbopelvic parameters and the height of disc space and L5-S1 neural foramen was performed before surgery as well as a month after surgery. Results Preoperatively, OLIF L5-S1 group and TLIF group showed similar lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS); (p=0.08, 0.48, 0.67, 0.19 and 0.12, respectively). Postoperatively those parameters did not show statistically significant differences between two groups (p=0.17, 0.32, 0.53, 0.16 and 0.19, respectively). In terms of disc and foraminal height, the OLIF L5-S1 group showed significant greater increase of posterior disc height and foraminal height (p=0.01 and 0.00). There was no significant differences between the two groups in mean VAS and ODI score over the follow-up period. Conclusion This study demonstrates that both OLIF L5-S1 group and TLIF L5-S1 group had similar ability of achieving lumbopelvic alignment however, increase of foraminal height was greater in patients with OLIF L5-S1 group.

BackgroundCopeptin has been reported as a predictive biomarker for the prognosis after traumatic brain injury (TBI). However, most of them were in patients with severe TBI and limited value in predicting outcomes in patients with moderate TBI defined as Glasgow Coma Scale (GCS) score from 9 to 12. We aimed to investigate the predictive value of copeptin in assessing the neurologic outcome following moderate TBI.MethodsPatients were prospectively enrolled between May 2017 and November 2020. We consecutively measured plasma copeptin within 24 h after trauma, days 3, 5, and 7 using ELISA. The primary outcome was to correlate plasma copeptin levels with poor neurologic outcome at 6 months after moderate TBI. The secondary outcome was to compare the prognostic accuracy of copeptin and C-reactive protein (CRP) in assessing the outcome of patient.ResultsA total of 70 patients were included for the final analysis. The results showed that 29 patients (41.4%) experienced a poor neurologic outcome at 6 months. Multivariable logistic regression analysis revealed that increased copeptin (odds ration [OR] = 1.020, 95% CI: 1.005–1.036), GCS score of 9 or 10 (OR = 4.507, 95% CI: 1.266–16.047), and significant abnormal findings on CT (OR = 4.770; 95% CI: 1.133–20.076) were independent risk factors for poor outcomes. Consecutive plasma copeptin levels were significantly different according to outcomes (p < 0.001). Copeptin on day 7 exhibited better prognostic performance than CRP with an area under receiver operating characteristic curve (AUROC) difference of 0.179 (95% CI: 0.032–0.325) in predicting 6-month poor outcomes.ConclusionPlasma copeptin level can be a useful marker in predicting 6-month outcomes in patients with moderate TBI.

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.

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.

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

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-a) showed a statistically nominal association with IA in both the overall, as well as East-Asian populations (0.01

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 highfat 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 highdensity 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 antiobesity 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This paper proposes a regression noise model that can cover the noise effect from N-coupled TSVs based on SPICE simulation and reliability analysis flow for high-level simulation using a regression model. Regression analysis is adopted to develop a simple noise model with a single parameter and use the superposition theorem to extend the number of TSV lines that produce the noise. The proposed regression model has over 99 percent accuracy with SPICE in the given parameter range. For the N-coupled TSV wire, the regression noise model has over 96 percent accuracy. This paper choose the transaction level simulation for the high-level proposed analysis flow to calculate the single bit error rate of over 100 billion transaction data in a few minutes. Our simulation result shows the effect of the N-coupled TSV crosstalk glitch noise on the single bit error rate when the probability function type of the manufacturing noise is considered. [ABSTRACT FROM AUTHOR]

Objective : Massive intracerebral hemorrhage (ICH) and major infarction (MI) are devastating cerebral vascular diseases. Decompression craniectomy (DC) is a common treatment approach for these diseases and acceptable clinical results have been reported. Author experienced the postoperative intracranaial pressure (ICP) trend is somewhat different between the ICH and MI patients. In this study, we compare the ICP trend following DC and evaluate the clinical significance. Methods : One hundred forty-three patients who underwent DC following massive ICH (81 cases) or MI (62 cases) were analyzed retrospectively. The mean age was 56.3±14.3 (median=57, male : female=89 : 54). DC was applied using consistent criteria in both diseases patients; Glasgow coma scale (GCS) score less than 8 and a midline shift more than 6 mm on brain computed tomography. In all patients, ventricular puncture was done before the DC and ICP trends were monitored during and after the surgery. Outcome comparisons included the ictus to operation time (OP-time), postoperative ICP trend, favorable outcomes and mortality. Results : Initial GCS (p=0.364) and initial ventricular ICP (p=0.783) were similar among the ICH and MI patients. The postoperative ICP of ICH patients were drop rapidly and maintained within physiological range if greater than 80% of the hematoma was removed. While in MI patients, the postoperative ICP were not drop rapidly and maintained above the physiologic range (MI=18.8 vs. ICH=13.6 mmHg, p=0.000). The OP-times were faster in ICH patients (ICH=7.3 vs. MI=40.9 hours, p=0.000) and the mortality rate was higher in MI patients (MI=37.1% vs. ICH=17.3%, p=0.007). Conclusion : The results of this study suggest that if greater than 80% of the hematoma was removed in ICH patients, the postoperative ICP rarely over the physiologic range. But in MI patients, the postoperative ICP was above the physiologic range for several days after the DC. Authors propose that DC is no need for the massive ICH patient if a significant portion of their hematoma is removed. But DC might be essential to improve the MI patients' outcome and timely treatment decision. [ABSTRACT FROM AUTHOR]

Intramuscular myxoma (IM) is a benign neoplasm of mesenchymal origin. We report a rare case of IM which was located in the lumbosacral paraspinal muscles. A 62-year-old female patient presented with progressive low back pain for 2 months, and the radiologic findings showed a large mass (4.0x3.5x6.5 cm) in the right lumbosacral paraspinal area. Total resection of the tumor was performed and the symptom was nearly resolved after surgery. Although the immuno-histopathological analysis was consistent with IM, there were some different findings from typical pathological characteristics of IM in this case. Firstly, the symptomatic change of the mass took relatively short time (less than 3 months), and this change was accompanied by partial calcification inside the mass. Moreover, iatrogenic interruption of paravertebral muscle by the other previous operation might be the promoting factor of the fibrous dysplasia, which can explain the pathogenesis of IM. To our knowledge, this is the eighth case of the lumbar paraspinal myxoma reported in the literatures and the first case in Asian population. [ABSTRACT FROM AUTHOR]

Objective : The purpose of this study was to investigate morphological change at the craniovertebral junction (CVJ) region using computed tomography. Methods : A total of 238 patients were included in this study, and mean age was 47.8±21.3 months. Spinal canal diameter, Power's ratio, McRae line, antero-posterior C1 ring height, atlantoaxial joint space, C2 growth, epidural space from the dens (M-PB-C2) and longitudinal distance (basion to C2 lower margin, B-C2) were measured. The mean value of each parameter was assessed for individual age groups. The cohorts were then divided into three larger age groups : infancy (I) (≤2 years), very early (VE) childhood (2-5 years) and early (E) childhood (5≥ years). Results : Spinal canal diameter increased with age; however, this value did not increase with statistical significance after VE age. A significant agerelated difference was found for all C2 body and odontoid parameters (p<0.05). Mean McRae line was 8.5, 8, and 7.5 mm in the I, VE, and E groups, respectively. The M-PB-C2 line showed up-and-down dynamic change during early pediatric periods. Conclusion : Expansion of the spinal canal was restricted to the very early childhood period (less than 5 years) in the CVJ region; however, the C2 body and odontoid process increased continuously with age. The above results induced a dynamic change in the M-PB-C2 line. Although C2 longitudinal growth continued with age, the McRae line showed relatively little change. [ABSTRACT FROM AUTHOR]

Objective In order to provide normal values of the pediatric sub-axial cervical spinal canal and vertebral body growth pattern using computed tomographic scans, a total of 318 patients less than 10 years old were included. Methods: The growth of the vertebral body and canal space was investigated using four different age groups. The Torg ratio (TR) was calculated and all patients were classified into a low TR group and a high TR group according to a cutoff value of 1.0. To account for spinal curvature, the C3-7 angle was measured. Results: Very little axial expansion and growth in height were observed (2.9 mm and 3.4 mm, respectively), and the spinal canal increments (1.8 mm) were much smaller than the dimensions of the vertebral body. The mean TR values were 1.03±0.14 at the C3 vertebral level, 1.02±0.13 at C4, 1.05±0.13 at C5, 1.04±0.13 at C6, and 1.02±0.12 at C7 in all patients. The mean sub-axial angle (C3-7) was 7.9±10.6° (range: -17-47°). Conclusion: The upper sub-axial spinal canal continuously increased in size compared to the lower sub-axial spine after 8 years of age. Considerable decrements in the TR was found after late childhood compared to younger ages. Generally, there were no significant differences between boys and girls in vertical length of the cervical vertebrae. However, the axial dimension of the vertebral body and the spinal canal space varied according to gender. [ABSTRACT FROM AUTHOR]

Spinal neurenteric cysts are uncommon congenital lesions, furthermore solitary neurenteric cysts of the upper cervical spine are very rare. A 15-yearold boy having an intraspinal neurenteric cyst located at cervical spine presented with symptoms of neck pain and both shoulders pain for 2 months. Cervical spine magnetic resonance (MR) imaging demonstrated an intradural extramedullary cystic mass at the C1-3 level without enhancement after gadolinium injection. There was no associated malformation on the MR imaging, computed tomography, and radiography. Hemilaminectomy at the C1-3 levels was performed and the lesion was completely removed through a posterior approach. Histological examination showed the cystic wall lined with ciliated pseudostratified columnar epithelium containing mucinous contents. Neurenteric cyst should be considered in the diagnosis of spinal solitary cystic mass. [ABSTRACT FROM AUTHOR]

Background: Carcinoma-associated fibroblasts (CAFs) contribute to carcinogenesis and cancer progression, although their origin and role remain unclear. We recently identified and investigated the in situ identity and implications of gastric submucosa-resident mesenchymal stem cells (GSMSCs) in the progression of gastric carcinogenesis. Methods: We isolated GS-MSCs from gastric submucosa using hydrogel-supported organ culture and defined their identity. Isolated cells were assessed in vitro by immunophenotype and mesengenic multipotency. Reciprocal interactions between GS-MSCs and gastric cancer cells were evaluated. To determine the role of GS-MSCs, xenografts were constructed of gastric cancer cells admixed with or without GS-MSCs. Results: Isolated cells fulfilled MSCs requirements in regard to plastic adherence, stromal cell immunophenotype, and multipotency. We demonstrated a paracrine loop that gastric cancer cells enhanced the migration, proliferation, and differentiation of GS-MSCs; additionally, GS-MSCs promoted the proliferation of gastric cancer cell in vitro. Xenograft experiments showed that GSMSCs significantly promoted cancer growth and angiogenesis. GS-MSCs that integrated into gastric cancer became not only CAFs but also rarely endothelial cells which contributed to the formation of cellular and vascular cancer stroma. Conclusions: Endogenous GS-MSCs play an important role in gastric cancer progression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Kallikrein-related peptidase 6 (KLK6) encodes a trypsin-like serine protease that is up-regulated in several cancers, although the putative functions of KLK6 in cancer have not been elucidated. In the current study, overexpression of KLK6 was identified in colon cancer, and the possibility that KLK6 may be a suitable candidate as a tumor marker was examined. METHODS: Messenger RNA (mRNA) transcript levels and protein up-regulation of KLK6 in colon cancer tissues was examined using reverse transcriptase-polymerase chain reaction, immunohistochemistry, and clinicopathologic analyses. Cell proliferation, invasiveness, and antiapoptotic activity were determined in colon cancer cells that were transfected with small-interfering RNA (siRNA) of KLK6. RESULTS: KLK6 mRNA was up-regulated significantly in tumor tissues compared with nontumor regions. KLK6 protein was strongly expressed in adenocarcinomas but was not expressed in normal mucosa or in premalignant dysplastic lesions. Sera from patients with colon cancer revealed an increase in KLK6 secretion (0.25 lg/mL; P = .031) compared with noncancer cells (0.19 µg/mL). Clinicopathologic and immunohistochemical studies of 143 patients with colon cancer revealed a significant correlation between KLK6 expression and Dukes disease stage (P = .005). High KLK6 expression was associated significantly with shorter overall (P = .001) and recurrence-free survival (P = .001). The rates of proliferation and invasiveness were decreased by 50% in cells that were transfected with KLK6 siRNA. The overexpression of KLK6 led to decreased activity of the E-cadherin promoter. CONCLUSIONS: KLK6 was up-regulated significantly in tissues and sera from patients with colon cancer and was associated closely with a poor prognosis, suggesting that KLK6 may be used as a potential biomarker and a therapeutic target for colon cancer. [ABSTRACT FROM AUTHOR]

Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1. [ABSTRACT FROM AUTHOR]

Polymer encapsulated inorganic metal oxide nanocomposites composed of poly(methyl methacrylate)/TiO2 were synthesized by the radical dispersion polymerization of methyl methacrylate in supercritical carbon dioxide. TiO2 nanoparticles, pretreated with 3-methacryloxypropyltrimethoxysilane were used to produce the nanocomposites. Relatively stable composite latexes were formed in supercritical carbon dioxide at 7.5% w/w TiO2 with respect to MMA in the presence of poly(dimethylsiloxane-b-methacrylic acid) stabilizer, which resulted in dry white powder. With increasing the ratio of TiO2/methyl methacrylate, the latexes became unstable and produced more agglomerated products. Transmission electron microscope images revealed that the nanoparticles were encapsulated as small agglomerate in poly(methyl methacrylate) particles. This facile method provides a way to develop solvent free composites with nanostructures. The composite particles were also confirmed by FT-IR spectroscopy, X-ray diffraction and thermogravimetric analysis. [ABSTRACT FROM AUTHOR]

The proangiogenic action of human adipose tissue-derived mesenchymal stem cells (hASCs) transplantation has been shown to be mediated by secretory factors. In this study, we determined if human granulocyte chemotactic protein-2(GCP2) or monocyte chemoattractant protein-1(MCP1) is involved in the proangiogenic action of hASCs transplantation in the hindlimb ischemia model. hASCs secrete GCP2 and MCP1, which leads to increased tubule formation. The downregulation of GCP2 or MCP1 decreased MCP1 and GCP2 secretion, respectively, whereas the external addition of GCP2 or MCP1 increased MCP1 and GCP2, respectively. Additionally, the treatment of GCP2 and MCP1 increased VEGF secretion, while the downregulation of GCP2 and MCP1 showed the opposite effect on VEGF secretion. Downregulation of GCP2 and MCP1 expression also inhibited hASCs-induced proangiogenic action, while the overexpression of GCP2 increased it. Finally, the downregulation of MCP1 or VEGF inhibited the GCP2 overexpression-induced increase in blood flow recovery. Taken together, these data indicate that the proangiogenic action of hASCs transplantation is mediated by the interaction between GCP2, MCP1 and VEGF, which are secreted from the transplanted cells. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

CKS2 was identified as an upregulated gene in gastric cancer via our DNA microarray. This study was to verify the upregulation of CKS2 in many gastric cancer patients and to examine the CKS2-mediated cellular response. CKS2 upregulation was analyzed using reverse transcriptase PCR, real-time PCR, and immunohistochemical and clinicopathological analyses. GFP-CKS2 or CKS2-siRNA was used to analyze the cellular localization and proliferation. The strong upregulation of mRNA and protein levels of CKS2 was identified. In CKS2-overexpressing cells, tumor suppressor p53 and p21cip1 were downregulated and cell growth was increased. In contrast, CKS2-siRNA-transfected cells showed an increased tumor suppressor expression and decreased cell growth. We showed that CKS2 was significantly upregulated in gastric cancers and a high level of CKS2 was highly correlated with histologic tumor differentiation and pathological grade of the tumor size, lymph node, and metastasis stage. We suggest that the cell cycle regulator CKS2 might be deeply involved in gastric cancer progression. [ABSTRACT FROM AUTHOR]

Combining hybrid nanostructures of metal nanoparticles (NPs) and carbon nanotubes could afford a novel strategy to prepare promising nanomaterials for the highly sensitive sensors and imaging science applications. Conventional acid oxidation process was used to obtain carboxylic acid bound multi-walled carbon nanotubes (MWNTs) which was further acylated with thionyl chloride to give acyl chloride functionalized MWNTs. Thiol functionalized MWNTs were synthesized by amidation reaction of the acylated MWNTs with cysteamine. Further, gold nanoparticles (GNPs) were successfully fabricated on the tube walls to yield the CNT/Au hybrid. Fourier transform infrared spectroscopy and energy dispersive X-ray studies were used to characterize the surface chemical functionalities and composition of MWNTs, respectively. Evidence for the attachment of GNPs to thiol functionalized MWNTs was obtained from ultraviolet–visible absorption spectra. In addition, TEM images provided a vivid image of uniform decoration of GNPs on the nanotube sidewalls. [ABSTRACT FROM AUTHOR]

NDRG (N-Myc downstream-regulated gene)-2 is a member of the NDRG family. Although it has been suggested that NDRG2 is involved in cellular differentiation and tumor suppression, its intracellular signal and regulatory mechanism are not well known. Here, we show the differential expression of NDRG2 in human colon carcinoma cell lines and tissues by reverse transcription–polymerase chain reaction and immunohistochemical analyses with monoclonal antibody against NDRG2. NDRG2 was strongly expressed in normal colonic mucosa and colonic adenomatous tissues (25 of 25) but not in all invasive cancer tissues [44 of 99 (44%)]. Most distinctive results indicated that the high expression level of NDRG2 has a positive correlation with tumor differentiation and inverse correlation with tumor invasion depth and Dukes’ stage of colon adenocarcinoma. To investigate the roles of NDRG2 in tumorigenesis, we used in vitro cell culture system. SW620 colon cancer cell line with a low level of intrinsic NDRG2 protein was transfected with NDRG2-expressing plasmid. TOPflash luciferase reporter assay showed that the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) was reduced by NDRG2 introduction, but not by the introduction of mutant NDRG2 generated by deletion or site-directed mutagenesis. Intracellular β-catenin levels were slightly reduced in the NDRG2-transfected SW620 cells and this regulation of β-catenin stability and TCF/LEF activity were mediated through the modulation of glycogen synthase kinase-3beta activity by NDRG2 function. Our results suggest that NDRG2 might play a pivotal role as a potent tumor suppressor by the attenuation of TCF/β-catenin signaling for the maintenance of healthy colon tissues. [ABSTRACT FROM AUTHOR]