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STUDY DESIGN: To demonstrate the existence of mesenchymal stem cells (MSCs) in ligamentum flavum (LF) and their pathogenic role in LF hypertrophy. OBJECTIVE: To isolate and characterize LF-derived MSCs and their response to transforming growth factor-beta 1 (TGF-[beta]1) and trichostatin A (TSA), a histone deacetylase inhibitor (HDACi). SUMMARY OF BACKGROUND DATA: LF is a connective tissue, of which hypertrophic changes induce spinal stenosis. The pathogenic role of TGF-[beta]1 in spinal stenosis has been implicated. TSA has been shown to suppress TGF-[beta]1-induced alpha-smooth muscle actin ([alpha]-SMA), type I and III collagen synthesis in a variety of cells. MSCs have been isolated from a variety of adult tissues, except LF. Whether MSCs exist in LF and their response to TGF-[beta]1 and TSA is not clear. METHODS: The MSCs from LF were isolated and cultured. Their phenotypic character, linage differentiation potential, and response to TGF-[beta]1 and TSA were analyzed. RESULTS: LF-derived MSCs have the similar profile of surface markers as bone marrow MSCs. They were demonstrated to have the potential to be differentiated into osteoblasts, adipocytes, and chondrocytes. Administration of TGF-[beta]1 stimulated cell proliferation, enhanced the gene expression of type I and III collagen, and increased the gene expression and protein level of [alpha]-SMA. TSA blocked the fibrogenic effects of TGF-[beta]1. CONCLUSION: The current results demonstrated the isolation of MSCs from LF. The cellular response to TGF-[beta]1 implied that these cells might play an important role in the pathogenesis of LF hypertrophy. TSA, which blocks the effects of TGF-[beta]1, may be a potent therapeutic choice for inhibiting LF hypertrophy. [ABSTRACT FROM AUTHOR]

Purpose: To compare the clinical efficacy and prognosis differences between conservative treatment and surgical treatment in patients with non-serious neurologically intact pyogenic spondylitis (Nsi-Nsni-PS), and to provide theoretical reference for the clinical treatment of Nsi-Nsni-PS patients., Methods: A retrospective analysis was conducted on 112 cases of Nsi-Nsni-PS patients treated in our hospital from June 2016 to June 2021. According to different treatment methods, they were divided into conservative treatment group (53 cases) and surgical treatment group (59 cases). The general data, laboratory tests, imaging examinations, length of hospital stay, duration of antibiotic use, VAS for pain before and after treatment, ODI, local kyphotic angle correction of diseased vertebrae, and recurrence rate were collected and analyzed in both groups. SPSS 26.0 statistical software was used for analysis. Measurement data were expressed as mean ± standard deviation, and independent sample t-test or rank sum test was used for comparison between groups, while variance analysis was used for intra-group comparison. Count data were expressed as number (%) and compared between groups using chi-square test or Fisher's exact test. Mann-Whitney U test was used to evaluate the changes in local kyphotic angle between the two groups. A p value < 0.05 was considered statistically significant., Results: There were no significant differences in general data and imaging characteristics between the two groups (P > 0.05); there were no statistically significant differences in the positive culture rate of pathogens, length of hospital stay, duration of antibiotic use, treatment complications, WBC, CRP, ESR levels at admission and discharge, VAS and ODI at admission and last follow-up between the two groups (P > 0.05). The WBC and CRP levels of patients in the conservative group at discharge were lower than those in the surgical group (P < 0.05), and there was no significant difference in the decrease in inflammatory indicators (WBC, CRP, ESR) between the two groups (P > 0.05). By the last follow-up, the neurological function of patients in both groups had significantly improved compared to admission (P < 0.05), with 12 out of 15 ASIA grade D patients in the conservative group recovering to grade E, and 21 out of 25 grade D patients in the surgical group recovering to grade E, with no worsening of neurological function in either group. The differences in VAS and ODI scores at the last follow-up compared to before treatment were statistically significant in both groups (P < 0.05), and all patients regained normal activity. Compared with before treatment, the correction degree of local kyphotic angle in the surgical group at the last follow-up was 0.93 ± 4.94°, slightly higher than that in the conservative group (-0.83 ± 3.37°), and the difference was statistically significant(P < 0.05)., Conclusions: During our follow-up, we found that both conservative and surgical treatments achieved satisfactory clinical outcomes in patients with Nsi-Nsni-PS. Compared to conservative treatment, surgical intervention did not demonstrate significant advantages in reducing hospitalization time and antibiotic usage duration, increasing pathogen culture positivity rate, lowering treatment complications, or controlling recurrence. However, surgical intervention showed superiority in correcting the local kyphotic angle of spinal lesions, albeit with relatively increased surgical trauma, risks, and treatment costs. At the last follow-up, the surgical group did not exhibit better long-term efficacy. Therefore, when formulating clinical treatment strategies for patients with Nsi-Nsni-PS, it may be preferable to prioritize conservative treatment, supplemented by the use of sensitive or empiric antibiotics for infection management, to improve patient prognosis., (© 2024. The Author(s) under exclusive licence to SICOT aisbl.)

Leukotriene B4 (LTB4) is a potent chemoattractant that can recruit and activate immune cells such as neutrophils, eosinophils, and monocytes to sites of inflammation. Excessive production of LTB4 has been linked to acute and chronic inflammatory diseases, including asthma, rheumatoid arthritis, and psoriasis. Inhibiting the binding of LTB4 to its receptors, BLT1 and BLT2, is a potential strategy for treating these conditions. While several BLT1 antagonists have been developed for clinical trials, most have failed due to efficacy and safety issues. Therefore, discovering selective BLT2 antagonists could improve our understanding of the distinct functions of BLT1 and BLT2 receptors and their pharmacological implications. In this study, we aimed to discover novel BLT2 antagonists by synthesizing a series of biphenyl analogues based on a BLT2 selective agonist, CAY10583. Among the synthesized compounds, 15b was found to selectively inhibit the chemotaxis of CHO-BLT2 cells with an IC 50 value of 224 nM without inhibiting the chemotaxis of CHO-BLT1 cells. 15b also inhibited the binding of LTB4 and BLT2 with a Ki value of 132 nM. Furthermore, 15b had good metabolic stability in liver microsomes and moderate bioavailability (F = 34%) in in vivo PK studies. 15b also showed in vivo efficacy in a mouse model of asthma, reducing airway hyperresponsiveness by 59% and decreasing Th2 cytokines by up to 46%. Our study provides a promising lead for the development of selective BLT2 antagonists as potential therapeutics for inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

BLT2 is a low-affinity leukotriene B 4 receptor that plays an essential role in the pathogenesis of various inflammatory diseases, including asthma and cancer. BLT2 is minimally expressed in a normal internal environment but is overexpressed in a stress-induced inflammatory environment. Recent research indicated that human BLT2 has two distinct forms. Although their functions are likely to be different, very few studies investigated these differences. Therefore, this paper will discuss about the two distinct forms of human BLT2; the short-form of BLT2 and the long-form of BLT2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei and Kim.)

Wernicke's encephalopathy (WE) is a severe life-threatening disease that occurs due to vitamin B1 (thiamine) deficiency (TD). It is characterized by acute mental disorder, ataxia, and ophthalmoplegia. TD occurs because of the following reasons: insufficient intake, increased demand, and long-term drinking due to corresponding organ damage or failure. Recent studies showed that oxidative stress (OS) can damage organs and cause TD in the brain, which further leads to neurodegenerative diseases, such as WE. In this review, we discuss the effects of TD caused by OS on multiple organ systems, including the liver, intestines, and brain in WE. We believe that strengthening the human antioxidant system and reducing TD can effectively treat WE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei and Xu.)

G protein-coupled receptors (GPCRs) have always been important drug targets in the pharmaceutical industry. One major question for the current GPCR drug discovery is how drugs have distinct efficacies at the same GPCR target. Related to this question, we studied how different ligands can have disparate efficacies at Leukotriene B 4 receptor (BLT2). By using molecular modeling studies, we predicted that Tyr271 6.51 located at TM6 of BLT2 performs as a key trigger for its activation and verified the prediction by site-directed mutagenesis, chemotactic motility studies, which included a chemical derivative of agonist CAY10583. We further identified Asn275 6.55 located at TM6 as a weak activation trigger in BLT2 and performed double mutation studies to confirm our computational results. Our results provide strong evidence for the exact mechanism of ligand efficacy at BLT2., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

A method to measure the superficial velocity of the water phase in gas-water flow using an electromagnetic flowmeter (EMF) and rotating electric field conductance sensors (REFCSs) is introduced in this paper. An electromagnetic flowmeter instrument factor model is built and the correlation between electromagnetic flowmeter output and gas holdup in different flow patterns are explored through vertical upward gas-water flow dynamic experiments in a pipe with an inner diameter (ID) of 20 mm. Water superficial velocity is predicted based on pattern identification among bubble, churn, and slug flows. The experimental results show that water superficial velocity can be predicted fairly accurately for bubble, churn, and slug flows with a water cut higher than 60% (absolute average percentage deviation and absolute average deviation are 4.1057% and 0.0281 m/s, respectively). The output of the electromagnetic flowmeter is unstable and invalid in slug flows with a water cut below 60% due to the non-conducting gas slug is almost filling the pipe. Therefore, the electromagnetic flowmeter is not preferred to be used in such conditions., Competing Interests: The authors declare no conflict of interest.

Background: Developing mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for therapy of non-alcoholic fatty liver disease (NAFLD). Polygonatum kingianum (PK) has been traditionally used in China as a medicinal and nutritional ingredient for centuries and can alleviate high-fat diet (HFD)-induced NAFLD by promoting mitochondrial functions. To date, the underlying molecular mechanism of PK for treating mitochondrial dysfunctions and thus alleviating NAFLD remains unclear., Aim: To identify the molecular mechanism behind the mitochondrial regulatory action of PK against HFD-induced NAFLD in rats., Methods: NAFLD model was induced in rats with HFD. The rats were intragastrically administered PK (4 g/kg per day) for 14 wk. Metabolites in hepatic mitochondrial samples were profiled through ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to find the potential biomarkers and metabolic pathways., Results: PK significantly restored the metabolites' levels in the mitochondrial samples. Ten potential biomarkers were identified in the analyzed samples. These biomarkers are involved in riboflavin metabolism., Conclusion: PK can alleviate HFD-induced NAFLD by regulating the riboflavin metabolism and further improving the mitochondrial functions. Thus, PK is a promising mitochondrial regulator/nutrient for alleviating NAFLD-associated diseases., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest associated with this manuscript., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: To identify the effects and mechanism of action of Polygonatum kingianum ( P. kingianum ) on dyslipidemia in rats using an integrated untargeted metabolomic method., Methods: A rat model of dyslipidemia was induced with a high-fat diet (HFD) and rats were given P. kingianum [4 g/(kg•d)] intragastrically for 14 wk. Changes in serum and hepatic lipid parameters were evaluated. Metabolites in serum, urine and liver samples were profiled using ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to identify potential biomarkers and metabolic pathways., Results: P. kingianum significantly inhibited the HFD-induced increase in total cholesterol and triglyceride in the liver and serum. P. kingianum also significantly regulated metabolites in the analyzed samples toward normal status. Nineteen, twenty-four and thirty-eight potential biomarkers were identified in serum, urine and liver samples, respectively. These biomarkers involved biosynthesis of phenylalanine, tyrosine, tryptophan, valine, leucine and isoleucine, along with metabolism of tryptophan, tyrosine, phenylalanine, starch, sucrose, glycerophospholipid, arachidonic acid, linoleic acid, nicotinate, nicotinamide and sphingolipid., Conclusion: P. kingianum alleviates HFD-induced dyslipidemia by regulating many endogenous metabolites in serum, urine and liver samples. Collectively, our findings suggest that P. kingianum may be a promising lipid regulator to treat dyslipidemia and associated diseases., Competing Interests: Conflict-of-interest statement: The authors declare that there is no duality of interest associated with this manuscript.

Mangrove degradation is a well-documented trend, but the spread of mangroves within the Siangshan Wetland in Hsinchu, Taiwan, runs contrary to that trend. The spread of mangroves changes the structure and functions of habitats for benthic organisms, causes infilling of estuaries and flooding and creates breeding grounds for small black mosquitoes. A large-scale mangrove-removal project was undertaken by the Hsinchu City Government from October 2015 to March 2016. They also investigated the consequences of mangrove removal on benthic organisms and adjacent habitats from October 2015 to September 2016, and the density, species count, Shannon-Wiener index ( H '), and Pielou's evenness index ( J ') of the mangrove and non-mangrove regions were compared. In this study, we used satellite telemetry images to monitor fluctuations in mangrove density from 2006 to 2016. The non-mangrove region exhibited more variations than the mangrove region. After mangrove removal, species returned to their original habitats and noteworthy biological values significantly increased in the mangrove regions. This study presents evidence to argue that mangrove removal benefits benthic organisms. The results indicate that mangrove removal can be an appropriate habitat rehabilitation strategy for benthic organisms. The ecological findings of this study can inform coastal managers or other officials who seek to steward mangrove biomass., Competing Interests: The authors declare there are no competing interests.

Wogonin, a naturally occurring bioactive monoflavonoid isolated from Scutellariae radix (roots of Scutellariae baicalensis Georgi), has known anticancer effects. However, the molecular signaling mechanism by which wogonin inhibits invasiveness in breast cancer cells remains unclear. In the present study, it was observed that wogonin exerted an inhibitory effect on the lipopolysaccharide (LPS)‑enhanced invasiveness of MDA‑MB‑231 cells. In addition, wogonin inhibited the synthesis of interleukin‑8 (IL‑8) and matrix metallopeptidase‑9 (MMP‑9), which are critical for promoting invasiveness in MDA‑MB‑231 cells. Wogonin also suppressed the expression of leukotriene B4 receptor 2 (BLT2) and the synthesis of its ligand, by inhibiting 5‑lipoxygenase (5‑LO) in LPS‑stimulated MDA‑MB‑231 cells. Notably, wogonin attenuated the production of IL‑8 and MMP‑9 by inhibiting the BLT2/extracellular signal‑regulated kinase (ERK)‑linked cascade. Finally, in vivo, LPS‑driven MDA‑MB‑231 cell metastasis was markedly suppressed by wogonin administration. Overall, the present results suggested that wogonin inhibited the 5‑LO/BLT2/ERK/IL‑8/MMP‑9 signaling cascade and demonstrated that this cascade may be an important target through which wogonin exerts its anticancer effects in breast cancer.

The molecular and cellular characteristics of male germ cell development remain largely unknown in corals. This study focused on the expression pattern of acetylated α-tubulin (Ac-α-Tu), which is involved in male germ cell development in various animals across taxa, to gain a better understanding of male germ cell development in the stony coral Euphyllia ancora. Immunohistochemical analysis of the different stages of male germ cells showed the presence of filamentous Ac-α-Tu in the early to late stages of male germ cells-such as spermatogonia, spermatocytes, and spermatids-as well as in the flagella of mature sperm. Immunocytochemical and transmission electron microscope analyses demonstrated that early-stage male germ cells possess long flagella containing Ac-α-Tu. The presence of filamentous Ac-α-Tu was also immunohistochemically demonstrated in the male germ cells from 14 other coral species, implying that possession of flagella with Ac-α-Tu is a common characteristic of male germ cells in stony corals. Therefore, as a distinctive cellular characteristic of male germ cells, Ac-α-Tu could be used as a male germ cell marker in stony corals; indeed, immunolabeling for Ac-α-Tu may be a useful method to aid in the identification and morphological observation of male germ cells in various corals in basic and applied biology (e.g., aquaculture) as well as in ecological studies., (© 2017 Wiley Periodicals, Inc.)

Recently, single-nucleotide polymorphisms (SNPs) in G-protein-coupled receptors (GPCRs) have been suggested to contribute to physiopathology and therapeutic effects. Leukotriene B 4 receptor 2 (BLT2), a member of the GPCR family, plays a critical role in the pathogenesis of several inflammatory diseases, including cancer and asthma. However, no studies on BLT2 SNP effects have been reported to date. In this study, we demonstrate that the BLT2 SNP (rs1950504, Asp196Gly), a Gly-196 variant of BLT2 (BLT2 D196G), causes enhanced cell motility under low-dose stimulation of its ligands. In addition, we demonstrated that Akt activation and subsequent production of reactive oxygen species (ROS), both of which act downstream of BLT2, are also increased by BLT2 D196G in response to low-dose ligand stimulation. Furthermore, we observed that the ligand binding affinity of BLT2 D196G was enhanced compared with that of BLT2. Through homology modeling analysis, it was predicted that BLT2 D196G loses ionic interaction with R197, potentially resulting in increased agonist-receptor interaction. To the best of our knowledge, this report is the first to describe a SNP study on BLT2 and shows that BLT2 D196G enhances ligand sensitivity, thereby increasing cell motility in response to low-dose ligand stimulation.

High-end graphics processing units (GPUs), such as NVIDIA Tesla/Fermi/Kepler series cards with thousands of cores per chip, are widely applied to high-performance computing fields in a decade. These desktop GPU cards should be installed in personal computers/servers with desktop CPUs, and the cost and power consumption of constructing a GPU cluster platform are very high. In recent years, NVIDIA releases an embedded board, called Jetson Tegra K1 (TK1), which contains 4 ARM Cortex-A15 CPUs and 192 Compute Unified Device Architecture cores (belong to Kepler GPUs). Jetson Tegra K1 has several advantages, such as the low cost, low power consumption, and high applicability, and it has been applied into several specific applications. In our previous work, a bioinformatics platform with a single TK1 (STK platform) was constructed, and this previous work is also used to prove that the Web and mobile services can be implemented in the STK platform with a good cost-performance ratio by comparing a STK platform with the desktop CPU and GPU. In this work, an embedded-based GPU cluster platform will be constructed with multiple TK1s (MTK platform). Complex system installation and setup are necessary procedures at first. Then, 2 job assignment modes are designed for the MTK platform to provide services for users. Finally, ClustalW v2.0.11 and ClustalWtk will be ported to the MTK platform. The experimental results showed that the speedup ratios achieved 5.5 and 4.8 times for ClustalW v2.0.11 and ClustalWtk, respectively, by comparing 6 TK1s with a single TK1. The MTK platform is proven to be useful for multiple sequence alignments., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

RanBPM is a scaffolding protein that regulates several cellular processes by interacting with various proteins. Previously, we reported that RanBPM acts as a negative regulator of BLT2, a low-affinity leukotriene B 4 receptor; thus, it interferes with BLT2-mediated cell motility. In the present study, we observed that the expression levels of RanBPM were markedly reduced in the highly aggressive MDA-MB-435 and MDA-MB-231 human breast cancer cell lines compared with those in non-invasive MCF-7 cells. Additionally, we found that the restoration of RanBPM levels suppressed the invasiveness of these aggressive breast cancer cells in a manner dependent on BLT2 activation. In contrast, the knockdown of endogenous RanBPM by shRNA strongly promoted invasiveness in non-invasive MCF-7 cells. We also observed that RanBPM suppressed the invasiveness of aggressive breast cancer cells by inhibiting BLT2-mediated reactive oxygen species (ROS) generation and IL-8 production. Taken together, our results suggest that RanBPM acts as a negative regulator of BLT2, thus attenuating the invasiveness of aggressive breast cancer cells., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Blastocystis is a common enteric protistan parasite that can cause acute, as well as chronic, infection and is associated with irritable bowel syndrome (IBS). However, the pathogenic status of Blastocystis infection remains unclear. In this study, we found that Blastocystis antigens induced abundant expression of proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α), in mouse intestinal explants, in mouse colitis colon, and in macrophages. Further investigation utilizing RAW264.7 murine macrophages showed that Blastocystis treatment in RAW264.7 macrophages induced the activation of ERK, JNK, and p38, the three major groups of mammalian mitogen-activated protein (MAP) kinases that play essential roles in the expression of proinflammatory cytokines. ERK inhibition in macrophages significantly suppressed both mRNA and protein expression of IL-6 and TNF-α and mRNA expression of IL-1β. On the other hand, JNK inhibition resulted in reductions in both c-Jun and ERK activation and significant suppression of all three proinflammatory cytokines at both the mRNA and protein levels. Inhibition of p38 suppressed only IL-6 protein expression with no effect on the expression of IL-1β and TNF-α. Furthermore, we found that serine proteases produced by Blastocystis play an important role in the induction of ERK activation and proinflammatory cytokine expression by macrophages. Our study thus demonstrated for the first time that Blastocystis could induce the expression of various proinflammatory cytokines via the activation of MAP kinases and that infection with Blastocystis may contribute to the pathogenesis of inflammatory intestinal diseases through the activation of inflammatory pathways in host immune cells, such as macrophages., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

BLT2, a low affinity receptor for leukotriene B4 (LTB4), is a member of the G protein-coupled receptor family and is involved in many signal transduction pathways associated with various cellular phenotypes, including chemotactic motility. However, the regulatory mechanism for BLT2 has not yet been demonstrated. To understand the regulatory mechanism of BLT2, we screened and identified the proteins that bind to BLT2. Using a yeast two-hybrid assay with the BLT2 C-terminal domain as bait, we found that RanBPM, a previously proposed scaffold protein, interacts with BLT2. We demonstrated the specific interaction between BLT2 and RanBPM by GST pulldown assay and co-immunoprecipitation assay. To elucidate the biological function of the RanBPM-BLT2 interaction, we evaluated the effects of RanBPM overexpression or knockdown. We found that BLT2-mediated motility was severely attenuated by RanBPM overexpression and that knockdown of endogenous RanBPM by shRNA strongly promoted BLT2-mediated motility, suggesting a negative regulatory function of RanBPM toward BLT2. Furthermore, we observed that the addition of BLT2 ligands caused the dissociation of BLT2 and RanBPM, thus releasing the negative regulatory effect of RanBPM. Finally, we propose that Akt-induced BLT2 phosphorylation at residue Thr(355), which occurs after the addition of BLT2 ligands, is a potential mechanism by which BLT2 dissociates from RanBPM, resulting in stimulation of BLT2 signaling. Taken together, our results suggest that RanBPM acts as a negative regulator of BLT2 signaling to attenuate BLT2-mediated cell motility.

Cancer is a leading cause of death worldwide and has been linked to inflammation. Leukotriene B4 (LTB4) is synthesized from arachidonic acid via the 5-lipoxygenase pathway and is a potent chemoattractant for inflammatory cells. LTB4 was recently shown to be associated with the pathogenesis of inflammatory diseases, including cancer. Of the two known LTB4 receptors, BLT1 and BLT2, the biological roles of the low-affinity LTB4 receptor 2, BLT2, have only recently been elucidated. This review focuses on recent discoveries regarding BLT2 and its roles in cancer progression and the downstream signaling mechanisms of the BLT2-linked signaling cascade in cancer cells. We believe that these findings will facilitate the development of new cancer treatments.

Special AT-rich sequence binding protein 2 (SATB2), a nuclear matrix attachment region-binding protein, can regulate embryonic development, cell differentiation, and cell survival. Previous studies showed that SATB2 is involved in osteoblast differentiation and skeletal development. In this study, we evaluated the role of SATB2 in oxidative stress-induced apoptotic insults to human osteoblast-like MG63 cells and mouse MC3T3-E1 cells. Exposure of MG63 cells to menadione increased intracellular reactive oxygen species levels in a concentration- and time-dependent manner. Simultaneously, menadione-induced oxidative stress triggered cell shrinkage and decreased cell viability. In addition, treatment of MG63 cells with menadione time-dependently decreased the mitochondrial membrane potential but enhanced caspase-3 activity. As a result, menadione-induced DNA fragmentation and cell apoptosis. As to the mechanism, exposure of MG63 cells to menadione amplified SATB2 messenger (m)RNA and protein expression in a time-dependent manner. Knockdown of translation of SATB2 mRNA using RNA interference led to chromatin disruption and nuclear damage. When MG63 cells and MC3T3-E1 cells were treated with SATB2 small interfering RNA, menadione-induced cell apoptosis was increased. We conclude that menadione causes oxidative stress in human osteoblasts and induces cellular apoptosis via a mitochondrion-caspase protease pathway. In addition, SATB2 may play a crucial role in protecting against oxidative stress-induced osteoblast apoptosis., (Copyright © 2012 Orthopaedic Research Society.)

12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid (12- HHT) is an enzymatic product of prostaglandin H(2) (PGH(2)) derived from cyclooxygenase (COX)-mediated arachidonic acid metabolism. Despite the high level of 12-HHT present in tissues and bodily fluids, its precise function remains largely unknown. In this study, we found that 12-HHT treatment in HaCaT cells remarkably down-regulated the ultraviolet B (UVB) irradiation-induced synthesis of interleukin-6 (IL-6), a pro-inflammatory cytokine associated with cutaneous inflammation. In an approach to identify the down-stream signaling mechanism by which 12-HHT down-regulates UVB-induced IL-6 synthesis in keratinocytes, we observed that 12-HHT inhibits the UVB-stimulated activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB). In addition, we found that 12-HHT markedly up-regulates MAPK phosphatase-1 (MKP-1), a critical negative regulator of p38 MAPK. When MKP-1 was suppressed by siRNA knock-down, the 12-HHT-mediated inhibitory effects on the UVB-stimulated activation of p38 MAPK and NF-κB, as well as the production of IL-6, were attenuated in HaCaT cells. Taken together, our results suggest that 12-HHT exerts anti-inflammatory effect via up-regulation of MKP-1, which negatively regulates p38 MAPK and NF-κB, thus attenuating IL-6 production in UVB-irradiated HaCaT cells. Considering the critical role of IL-6 in cutaneous inflammation, our findings provide the basis for the application of 12-HHT as a potential anti-inflammatory therapeutic agent in UV-induced skin diseases.

The influence of physical characteristics of electrospun three-dimensional (3D) fibrous scaffolds based on polybutylene succinate-co-adipate (PBSA) and poly l-lactic acid (PLLA) on the culture of primary human chondrocytes (PHCs) in terms of cell attachment, proliferation, and re-differentiation was investigated. Physical characteristics assessed for two polymers electrospun at two different delivery rates (PBSA-3, PBSA-16, PLLA-3, and PLLA-16) including average fiber diameter, average pore diameter, porosity, and contact angle. Results demonstrated that 3D fibrous scaffolds are better for PHCs' attachment than two-dimensional (2D) casting films made of the same polymeric materials. It was also found that 3D fibrous scaffolds are appropriate architecture for the proliferation of PHCs than 2D casting films and dependent upon the polymer used. Histological analysis revealed that a significant amount of PHC was found to be growing only within layers of PLLA fibrous scaffolds. The mitochondrial ribonucleic acid (mRNA) expression of both aggrecan and type II collagen by PHCs cultured in tissue culture polystyrene for 28 days decreased significantly. The mRNA expression of both aggrecan and type II collagen by PHCs cultured in PBSA scaffolds increased from 14 to 28 days, whereas only mRNA expression of aggrecan cultured in both PLLA scaffolds increased from 14 to 28 days.

BLT2, a low-affinity leukotriene B(4) (LTB(4)) receptor, is a member of the G protein-coupled receptor family and is involved in multiple cellular responses, including chemotaxis. Despite its biological significance, the mechanisms of BLT2 regulation, especially by protein kinases, are poorly characterised. In this study, we found that Akt phosphorylates BLT2 at its C-terminal Thr(355) residue and that this event is critical for BLT2-mediated chemotactic responses. In addition, we found that Rac1 stimulation and subsequent reactive oxygen species (ROS) production lie downstream of BLT2 phosphorylation, thus mediating chemotaxis., (Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Objectives: This study attempted to characterise the in-vitro release profiles of fenofibrate (FFB) from a self-microemulsifying drug-delivery system (SMEDDS) for optimising formulation factors and dissolution conditions for in-vivo absorption., Methods: The study was conducted by profiling the release of FFB formulated with either a complete solution or a micronised dispersion system (MDS) in a SMEDDS composed of medium-chain triglyceride (MCT) oil and surfactant mixtures S(mix) of TPGS and Tweens at different ratios (K(m) =TPGS/Tweens), with and without adding water. Optimised FFB SMEDDS formulations were then selected for in-vivo bioavailability study., Key Findings: The release rates of FFB from TPGS/Tween 20 systems were faster than those from TPGS/Tween 80 systems at the same K(m) value. In both systems, the release rates of FFB increased with a decrease in the K(m) value. Furthermore, both the release rates and the amounts of FFB from MDS in the water medium decreased with an increasing percentage of S(mix) added to both water contents. However, the release rates and amounts of FFB from MDSs increased with an increasing percentage of S(mix) in a 0.025 M sodium lauryl sulfate (SLS) solution. It was further illustrated that the release of FFB from SMEDDSs was complete within 30 min in both the 0.025 M SLS solution and water medium, but the release of FFB from Tricor® or MDSs was limited in water medium. An optimised FFB SMEDDS with either Tween 20(E5(20)) or Tween 80(E5(80)) and one MDS were selected for a pharmacokinetic study to compare with Tricor(®). The results demonstrated that the area under the receiver operating curve and C(max) values were in the order of Tricor(®) > E5(80)≅E5(20) > MDS and Tricor(®)≅E5(80) > E5(20) > MDS, respectively. Conclusions  The absorption of drug carried by SMEDDS might not be enhanced as a result of the smaller volume of water taken with oral administration of SMEDDSs and the agitation rate of the gastrointestinal tract not being strong enough to efficiently promote the self-microemulsification process to facilitate the in-vivo dissolution rate., (© 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.)

Recent studies have suggested that mast cells have critical roles in angiogenesis. However, the detailed mechanism by which mast cells contribute to angiogenesis is not yet clearly understood, especially in response to proinflammatory cytokines. In this study, we showed that the proinflammatory cytokine IL-1beta induces the synthesis of IL-8, a potent angiogenic factor, in human mast cells via the leukotriene B(4) receptor (BLT)2. We also characterized the BLT2 downstream signaling pathway and determined that BLT2-mediated IL-8 synthesis involves the upregulation of Nox1, a member of the NADPH oxidase family, Nox1-dependent reactive oxygen species generation and the subsequent activation of the redox-sensitive transcription factor NF-kappaB. For instance, knockdown of BLT2 and Nox1 with specific small interfering RNA, treatment with a specific BLT2 antagonist, LY255283, or treatment with a potential Nox inhibitor, diphenylene iodonium, suppressed IL-1beta-induced IL-8 synthesis. We found that the conditioned media collected from IL-1beta-treated human mast cell line HMC-1 had significantly enhanced angiogenic activity that could be dramatically attenuated by either small interfering RNA knockdown of BLT2 or treatment with neutralizing Ab to IL-8. Finally, the experiments were repeated using human primary cord blood-derived mast cells, and the results were clearly reproduced. Taken together, our results suggest that BLT2-Nox1-reactive oxygen species-dependent pathway plays a role in promoting the secretion of IL-8 from human mast cells in response to the proinflammatory cytokine IL-1beta, thus contributing to angiogenesis.

Distinguishing ventricular extrasystoles from normal heartbeats is crucial to cardiac arrhythmia analysis. This paper proposes novel morphological descriptors, the major portrait partition area (MPPA) and point distribution percentage (PDP), which are extracted from the reconstructed phase space of the QRS complex. These measures can be linked to QRS width and prolonged ventricular contraction, and offer several advantages over traditional characterization of the QRS structure: it does not require QRS boundary detection, is robust under R-peak misalignment, and including some information from nearby points. The first four principal components of MPPA variables and PDPs in the first and the third quadrants of the phase space diagram were used as inputs of neural networks. The performance of networks in distinguishing premature ventricular contraction events from normal heartbeats were evaluated under a series of 50 cross-validations based on the electrocardiogram data taken from the MIT/BIH arrhythmia database. The sensitivity and specificity obtained using the aforementioned MPPA principal components and PDPs as inputs were similar to those obtained using wavelet features and Hermite coefficients. However, the phase space information performed better in situations of noise contaminations and waveform deformations.

Fifty-two patients with unstable fractures of distal clavicle treated by open reduction and internal fixation with hook plates or tension band wires were retrospectively reviewed. The 52 patients were divided into two groups based on the method of treatment. The hook plate (HP) group included 32 patients and the tension band wire (TBW) group included 20 patients. Both groups were similar in respect to injury mechanisms, compounding medical conditions, and shoulder score (p > 0.1). However, hook plating had a significantly lower rate of complication (p = 0.01) and symptomatic hardware (p = 0.001). In addition, hook plating better facilitated the return to work and athletic activity (p = 0.004 and p = 0.003, respectively). In conclusion, if surgery of distal clavicular fractures is indicated, internal fixation with a hook plate has more advantages than with tension band wires.

Algorithm visualization is a unique research topic that integrates engineering skills such as computer graphics, system programming, database management, computer networks, etc., to facilitate algorithmic researchers in testing their ideas, demonstrating new findings, and teaching algorithm design in the classroom. Within the broad applications of algorithm visualization, there still remain performance issues that deserve further research, e.g., system portability, collaboration capability, and animation effect in 3D environments. Using modern technologies of Java programming, we develop an algorithm visualization and debugging system, dubbed GeoBuilder, for geometric computing. The GeoBuilder system features Java's promising portability, engagement of collaboration in algorithm development, and automatic camera positioning for tracking 3D geometric objects. In this paper, we describe the design of the GeoBuilder system and demonstrate its applications.

Objective: To study the degree and changes of cervical spinal canal stenosis by MRI scans in flexion and extension of the cervical vertebrae., Methods: Thirty cases of cervical stenosis included 13 male and 17 female with an average age of 39 years ranging from 28 to 66 years. The sagittal diameter of cervical spinal canal were below 10 mm (absolute stenosis) in 12 cases,within 10 to 12 mm (correspondence stenosis) in 18 cases. MRI scans in neutrality, flexion, extension performanced and the degree of cervical spinal canal stenosis and the changes of spinal cord compression were evaluated after MRI scans obtained., Results: Nineteen patients of extension occurrenced stenosis more serious, 8 patients of flexion occurrenced (P < 0.05)., Conclusion: For the cervical stenosis imaging diagnostic, flexion and extension of cervical MRI scan can be used to supplement conventional MRI examination neutral position, and the extension of MRI is more sensitivity than neutral position and flexion bit.

In order to improve the spatial resolution achieved by magnetic force microscopy (MFM) technique and its derivatives, we employ here advanced MFM tips fabricated by means of focused ion beam (FIB) milling. The magnetic coating applied on these tips is a CoCr film of 10 nm thickness. The MFM measurements on hard disk test samples reveal the achieved high resolution, and the measurement on a garnet film demonstrates the low invasiveness. High-frequency MFM (HF-MFM) is a development of the MFM technique to observe the HF stray fields emerging from magnetic recording writer poles at their operating conditions. By means of HF-MFM, magnetic recording writer poles are characterized in the frequency range 100-1,000 MHz. Up to now, all HF-MFM experiments conducted were using standard MFM cantilevers. From the HF-MFM images obtained using the advanced MFM cantilevers, it is clearly seen that the spatial resolution is considerably improved over the images obtained using standard MFM tips. However, the 10 nm thick magnetic coating of the cantilevers is found to work properly only at frequencies of up to about 500 MHz.

This report presents a case of direct injury to the dorsal sensory branch of the ulnar nerve caused by arthroscopic repair of the triangular fibrocartilage complex. The dorsal sensory branch of the ulnar nerve was strangulated by one of the three pull-out sutures of the joint capsule, just ulnar to the extensor carpi ulnaris tendon. Pain and dysaesthesia of the ulnar side of the wrist was completely relieved after excision of the injured nerve segment. This complication can be avoided by careful exploration of the dorsal sensory branch of the ulnar nerve prior to suturing or passage of instruments during arthroscopy.

Analysis of the indicator synthesis was studied by catalytic spectrophotometry, and the reducing decolorization that the copper(II) catalyzed the ration between ascorbic acid and 3-methyl-4-amino-4'-nitro azobenzol was discussed. Reaction condition was optimized and a highly selective determination of trace copper(II) was established. The detection limit was 0.048 microgram.L-1 for copper (II). The method has been used for determining trace copper(II) in human hair and aluminum alloy samples with satisfactory results.

Simple (unicameral or solitary) bone cysts are the only true cysts of primary intraosseous origin. These cysts involve the metaphysis of long tubular bones such as the proximal humerus and proximal femur and, occasionally, the proximal tibia, distal femur, patella, ilium, rib, and calcaneus. They are very rarely found in vertebrae, especially in the cervical vertebral spinous process and laminae. We report a 14-year-old boy with an expansile, bubbly cystic lesion in the spinous process and laminae of the seventh cervical vertebra. Histopathologic examination showed a cyst surrounded by thin fibrous or fibro-osseous wall without any lining epithelial cells, compatible with a simple bone cyst. As far as we know, this is the first case of simple bone cyst involving the spinous process and laminae of a cervical vertebra reported in Taiwan.

Hysteresis is a unique type of dynamic, which contains an important property, rate-independent memory. In addition to other memory-related studies such as time delay neural networks, recurrent networks, and reinforcement learning, rate-independent memory deserves further attention owing to its potential applications. In this paper, we attempt to define hysteretic memory (rate independent memory) and examine whether or not it could be modeled in neural networks. Our analysis results demonstrate that other memory-related mechanisms are not hysteresis systems. A novel neural cell, referred to herein as the propulsive neural unit, is then proposed. The proposed cell is based on a notion related the submemory pool, which accumulates the stimulus and ultimately assists neural networks to achieve model hysteresis. In addition to training by backpropagation, a combination of such cells can simulate given hysteresis trajectories.