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Chronic neuroinflammation is a pathological feature of neurodegenerative diseases. Inhibition of microglia-mediated neuroinflammation might be a potential strategy for neurodegeneration. Matairesinol, a dibenzylbutyrolactone plant lignan, presents in a wide variety of foodstuffs. It has been found to possess anti-angiogenic, anti-oxidative, anti-cancer and anti-fungal activities. In the present study, we investigated the anti-neuroinflammation effects of matairesinol on lipopolysaccharide (LPS)-induced BV2 microglia cells and the related molecular mechanisms. The results showed that matairesinol inhibited microglia activation by reducing the production of nitric oxide, the expression of inducible nitric oxide synthase and cyclooxygenase-2 in a concentration-dependent manner (6.25, 12.5, 25 μM). In the molecular signaling pathway, LPS-induced nuclear factor-kappa B (NF-κB) transcriptional activity and translocation into the nucleus were remarkably suppressed by matairesinol through the inhibition of the extracellular signal-regulated kinase (ERK)1/2 signal transduction pathways, but not p38 MAPK or c-jun N-terminal kinase (JNK). Meanwhile, matairesinol also blocked LPS-mediated microglia migration and this was associated with inhibition of LPS-induced Src phosphorylation as well as Src expression in a concentration-dependent manner. Taken together, these results suggest that matairesinol inhibited inflammatory response and migration in LPS-induced BV2 microglia, and the mechanisms may be associated with the NF-κB activation and modulation of Src pathway.

The objective of the current study was to evaluate the anti-inflammatory effects of shizukaol B, a lindenane-type dimeric sesquiterpene isolated from the whole plant of Chloranthus henryi, on lipopolysaccharide (LPS)-induced activation of BV2 microglial cells in vitro. Our data showed that shizukaol B concentration-dependently suppressed expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), production of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in LPS-stimulated BV2 microglia. Meanwhile, shizukaol B concentration- and time-dependently inhibited LPS-mediated c-Jun N-terminal kinase 1/2 (JNK) activation, but had little effect on extracellular signal-regulated kinase 1/2 or p38 phosphorylation. Furthermore, shizukaol B significantly blocked LPS-induced activator protein-1 (AP-1) activation, evidenced by reduced phosphorylation and nuclear translocation of c-Jun and DNA binding activity of AP-1. Taken together, our findings suggest that shizukaol B exerts anti-inflammatory effects in LPS-activated microglia partly by modulating JNK-AP-1 signaling pathway.

The production of zinc-bearing solid dust is up to 4%~8% of total crude steel in steel plant, which is difficult to be recycled in traditional methods. To fully utilize the resources and reduce environmental pollutions, Chinese steel plants are using rotary hearth furnace (RHF) process to recycle solid dust. A consequential life-cycle inventory was carried out to assess the impact of dust recovery on greenhouse gas emissions based on the local production status. In the study system, the selected steel plant named a which have 10.5 million tons of Crude steel productivity and 0.48 million tons solid dust come out meanwhile. To research, a RHF production line of 0.3 million tons directly reduced iron (DRI) a year was established to recycle the solid dust. The DRI will be obtained from RHF and sent to the blast furnace as raw materials to reduce the demand for iron ore and coke in steelmaking processes. By researching on the life-cycle inventory in the system, the steelmaking process with RHF was 2299.3kgCO2/ton steel. It’s a little higher while compared with the process without RHF, which data is 2297.0 kgCO2/ton steel. The small production of DRI make a small difference to reduce the carbon footprint of steelmaking process, the added carbon footprint of RHF process is more than BF and other steelmaking processes reduced. It is concluded that dust recovery has no contribution to the greenhouse gas emission reductions in the technic condition of Chinese steel plants currently.

The objective of this study was to investigate the mechanical characteristics of implant–abutment interface design in a dental implant system, using nonlinear finite element analysis (FEA) method. This finite element simulation study was applied on three commonly used commercial dental implant systems: model I, the reduced-diameter 3i implant system (West Palm Beach, FL, USA) with a hex and a 12-point double internal hexagonal connection; model II, the Semados implant system (Bego, Bremen, Germany) with combination of a conical (45° taper) and internal hexagonal connection; and model III, the Brånemark implant system (Nobel Biocare, Gothenburg, Sweden) with external hexagonal connection. In simulation, a force of 170 N with 45° oblique to the longitudinal axis of the implant was loaded to the top surface of the abutment. It has been found from the strength and stiffness analysis that the 3i implant system has the lowest maximum von Mises stress, principal stress and displacement while the Brånemark implant system has the highest. It was concluded from our preliminary study using nonlinear FEA that the reduced-diameter 3i implant system with a hex and a 12-point double internal hexagonal connection had a better stress distribution, and produced a smaller displacement than the other two implant systems.

Xiao Nie,1,* Yi Shao,2,* Si-yu Liu,3 Hai-jun Li,1 Ai-lan Wan,4 Si Nie,1 De-chang Peng,1 Xi-jian Dai1,5 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 2Department of Ophthalmology,The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 3Medical College of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 4Department of Psychosomatic Medicine, The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 5Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China *These authors contributed equally tothis work Objective: The aim of this study is to explore the resting-state functional connectivity (FC) differences between the paired default mode network (DMN) subregions in patients with primary insomnia (PIs).Methods: Forty-two PIs and forty-two age- and sex-matched good sleepers (GSs) were recruited. All subjects underwent the resting-state functional magnetic resonance imaging scans. The seed-based region-to-region FC method was used to evaluate the abnormal connectivity within the DMN subregions between the PIs and the GSs. Pearson correlation analysis was used to investigate the relationships between the abnormal FC strength within the paired DMN subregions and the clinical features in PIs.Results: Compared with the GSs, the PIs showed higher Pittsburgh Sleep Quality Index score, Hamilton Anxiety Rating Scale score, Hamilton Depression Rating Scale score, Self-Rating Depression Scale score, Self Rating Anxiety Scale score, Self-Rating Scale of Sleep score, and Profile of Mood States score (P

1. It has been reported that resveratrol exerts the inhibitory effects on aging through activation of sirtuin 1 (SIRT1) and dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway involved in the high glucose-induced endothelial cell senescence. 2. The aims of this work were to explore whether BTM-0512, a novel derivative of resveratrol, was able to exert the beneficial effect on high glucose-induced cellular senescence through regulating the DDAH/ADMA pathway and to explore whether the regulatory effect of BTM-0512 on DDAH/ADMA pathway was related to the activation of SIRT1. 3. The senescence model of endothelial cells was induced by high glucose and the cells were collected for the determination of beta-galactosidase and DDAH activity, ADMA level, DDAH and SIRT1 mRNA expression. 4. The results showed that high glucose significantly increased the ratio of senescent cells concomitantly with the decreased DDAH activity, the downregulated DDAH2 and SIRT1 mRNA expressions and the increased ADMA levels, which were attenuated by pretreatment with BTM-0512. 5. The beneficial effects of BTM-0512 on high glucose-induced senescence were blocked by splimtomicin, the specific inhibitor of SIRT1, or by silencing DDAH2 expression. 6. The results suggest that BTM-0512 was able to exert the beneficial effects on high glucose-induced cellular senescence through regulating the DDAH/ADMA pathway, and its regulatory effect on DDAH/ADMA pathway was related to the activation of SIRT1.

The intrinsic polysulfides shuttle, resulting from not only concentration-gradient diffusion but also slow conversion kinetics of polysulfides, bears the primary responsibility for the poor capacity and cycle stability of lithium–sulfur batteries (LSBs). Here, it is first presented that enriched edge sites derived from vertical standing and ultrathin 2D layered metal selenides (2DLMS) can simultaneously achieve the thermodynamic and kinetic regulation for polysulfides diffusion, which is systematically elucidated through theoretical calculation, electrochemical characterization, and spectroscopic/microscopic analysis. When employed to fabricate compact coating layer of separator, an ultrahigh capacity of 1338.7 mA h g−1 is delivered after 100 cycles at 0.2 C, which is the best among the reports. Over 1000 cycles, the cell still maintains the capacity of 546.8 mA h g−1 at 0.5 C. Moreover, the cell exhibits outstanding capacities of 1106.2 and 865.7 mA h g−1 after 100 cycles at stern temperature of 0 and −25 °C. The superior low-temperature performance is appealing for extended practical application of LSBs. Especially, in view of the economy, the 2DLMS is recycled as an anode of lithium-ion and sodium-ion batteries after finishing the test of LSBs. The low-cost and scalable 2DLMS with enriched egde sites open a new avenue for the perfect regulation of the sulfur electrode.

Our previous studies showed that rutaecarpine (Rut) protected against myocardial ischemia/reperfusion (I/R) injury, which was associated with activation of transient receptor potential vanilloid subtype 1 (TRPV1). Recently, TRPV1 activation was also reported to exert neuroprotective effects. The present study was to investigate the effect of Rut on hypoxia/reoxygenation (H/R)-induced apoptosis in primary rat hippocampal neurons. Three-hour hypoxia (1% O2) and consequent 24-h reoxygenation significantly increased the apoptotic death of hippocampal neurons as evidenced by increases in both TUNEL-positive cell number and caspase-3 activity. However, pretreatment with Rut (1–10 mM) or caspase-3 specific inhibitor DEVD-CHO could markedly attenuate H/R-induced apoptosis in neurons. Rut markedly induced the phosphorylation of Akt and PI3K inhibitor LY294002 prevented the survival effect of Rut on neurons. Intracellular oxidative stress was significantly induced after H/R, which was inhibited by Rut and LY294002 as well as antioxidant PDTC. TRPV1 antagonist capsazepine or intracellular Ca 2þ chelator BAPTA/AM could abolish these effects of Rut mentioned above. In summary, the present data suggest that Rut inhibits H/R-induced apoptosis of hippocampal neurons via TRPV1-[Ca 2þ ]i-dependent and PI3K/Akt signaling pathway, which is related to inhibiting oxidative stress and caspase-3 activation.

BACKGROUND. Recent work has demonstrated that methyl methansulfonate and ultraviolet-sensitive gene clone 81 (Mus81) is critical in the maintenance of chromosome stability and tumor suppression in mice. To investigate its role in human hepatocellular carcinoma (HCC), which currently is unknown, the authors examined the correlation between Mus81 expression and prognosis in patients with HCC. METHODS. Reverse transcriptase-polymersase chain reaction and Western blot analyses were used to determine Mus81 expression levels in 41 paired HCC and paracarcinomatous liver tissue (PCLT) specimens. Immunohistochemistry analysis was also performed on 104 HCC specimens from patients with follow-up information. RESULTS. Both Mus81 messenger RNA and protein expression levels were decreased significantly in HCC specimens. Moreover, lower Mus81 expression levels were detected in nodular HCC (NHCC) than in solitary large HCC (SLHCC) specimens. Among 104 specimens of HCC, the positive rate of Mus81 was significantly lower than the rate in PCLT (P = .017), and the decreased Mus81expression was correlated significantly with high Edmondson-Steiner grade, multiple tumor nodes, and venous invasion. Patients with HCC who had low Mus81 expression had either poorer disease-free survival or poorer overall survival than patients who had with high Mus81 expression (P = .0027 and P = .0001, respectively). Multivariate Cox regression analysis revealed that low Mus81 expression was an independent prognostic factor for patients with HCC (risk ratio, 5.74; P = .012). CONCLUSIONS. Mus81 expression levels were decreased significantly in HCC specimens, and the decreased levels were correlated with a poor prognosis in patients with HCC, implicating Mus81 as a candidate prognostic marker in HCC. Cancer 2008. © 2008 American Cancer Society.

Neuroinflammation underlies the pathogenesis and progression of neurodegenerative diseases. 2׳-hydroxy-4,3׳,4׳,6׳-tetramethoxychalcone (HTMC) is a known chalcone derivative isolated from Chloranthus henryi with anti-inflammatory activities in BV2 macrophages. However, its pharmacological effects on microglial cells have not been demonstrated. To this end, we examined the effects of HTMC on lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglial cells. HTMC concentration-dependently inhibited LPS-induced expression of inflammatory enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nitric oxide (NO) production, and the secretion of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. In addition, HTMC inhibited reactive oxygen species (ROS) production by reducing NADPH oxidase (Nox) 2 and Nox4 expression. In addition, HTMC interfered LPS-induced c-Jun N-terminal kinase 1/2 (JNK) phosphorylation in a time- and concentration-dependent manner. By inhibiting phosphorylation and nuclear translocation of Jun, HTMC suppressed LPS-induced activator protein-1 (AP-1) activation. Taken together, our data indicate that HTMC suppresses inflammatory responses in LPS-stimulated BV2 microglial cells by modulating JNK-AP-1 and NADPH oxidases-ROS pathways. HTMC represents a promising therapeutic agent for neurodegenerative and related aging-associated diseases.

Transforming growth factor-β (TGF-β)/Smad signaling has been implicated in connective tissue growth factor (CTGF) expression in vascular smooth muscle cells (VSMC). Reactive oxygen species (ROS) are involved in activation of TGF-β/Smad signaling. However, detailed mechanisms underlying the process remain unclear. In present study, we demonstrated TGF-β1 strongly induced CTGF expression, Smad3 activation, NADPH oxidase 4 (Nox4) expression and increased ROS production in primary rat VSMC in vitro. NADPH oxidases inhibitor diphenylene iodonium (DPI) eliminated TGF-β1-induced CTGF expression and ROS generation. In addition, small-interfering RNA (siRNA) silencing of Smad3 or Nox4 significantly suppressed TGF-β1-mediated CTGF expression in VSMC. Furthermore, Nox4 silencing or inhibition eliminated TGF-β1-induced Smad3 activation and interaction between Nox4 and Smad3. In vivo studies further identified a positive correlation of Nox4 levels with Smad3 activation and CTGF expression in atherosclerotic arteries of patients and animal models. These data established that a novel mechanistic link of Nox4-dependent activation of Smad3 to increased TGF-β1-induced CTGF in the process of vascular remodeling, which suggested a new potential pathway for therapeutic interventions.

Background Reactive oxygen species (ROS) is thought as a major reason of vascular injury in diabetes. Vascular peroxidase 1 (VPO1) is a newly found peroxidase playing an important role in inducing oxidative stress. In the present experiment, we tested the role of VPO1 in senescence of endothelial cells in streptozotocin (STZ)-induced diabetic rats and cultured endothelial cells. Methods Blood samples were collected from carotid arteries. Vasodilator responses to acetylcholine (Ach) in the isolated aortic rings were measured, serum concentration of glucose, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and the expression of VPO1 in the aorta were determined. Endothelial cells were treated with high glucose or H 2 O 2 , the concentrations of MCP-1, TNF-α and hypochlorous acid (HOCl) and the expression of VPO1 were determined. shRNA of VPO1 was used for mechanism research in cultured cells. Results Vasodilator responses to Ach were impaired markedly and the serum concentrations of glucose, TNF-α and MCP-1 were significantly increased in diabetic rats. The expression of VPO1 in the aorta was upregulated in diabetic rats. High glucose treatment significantly decreased cell viability and elevated the levels of MCP-1, TNF-α and HOCl and upregulated the expression of VPO1. H 2 O 2 treatment significantly induced cellular senescence, inhibited eNOS expression and NO production. The effects of high glucose and H 2 O 2 were attenuated by shRNA interference of VPO1. Conclusions VPO1 plays an important role in senescence of endothelial cells and endothelial dysfunction by induction of oxidative stress and inflammatory reaction in type 2 diabetic rats.

Endothelial progenitor cells (EPCs) are involved in the repair of vessels and angiogenesis and are useful in the treatment of ischemic diseases. The dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is regulated by silent information regulator 1 (SIRT1), leading to the senescence of endothelial cells (ECs). Here, we demonstrated that peripheral blood EPCs predominantly expressed DDAH2 that increased with EPC differentiation. EPC senescence and dysfunction were induced on interruption of DDAH2 expression, whereas the mRNA expression of vascular endothelial growth factor (VEGF) and kinase-domain insert containing receptor (KDR) were downregulated. Moreover, SIRT1 expression increased with EPC differentiation. Interruption of SIRT1 inhibited DDAH2, VEGF, and KDR expression, but had no effect on the level of ADMA. From our data, we concluded that DDAH2 is involved in the differentiation of EPCs and regulates the senescence and function of EPCs through the VEGF/KDR pathway by activation of SIRT1.

Endothelial progenitor cells (EPCs) are involved in the repair of vessels and angiogenesis and are useful in the treatment of ischemic diseases. The dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway is regulated by silent information regulator 1 (SIRT1), leading to the senescence of endothelial cells (ECs). Here, we demonstrated that peripheral blood EPCs predominantly expressed DDAH2 that increased with EPC differentiation. EPC senescence and dysfunction were induced on interruption of DDAH2 expression, whereas the mRNA expression of vascular endothelial growth factor (VEGF) and kinase-domain insert containing receptor (KDR) were downregulated. Moreover, SIRT1 expression increased with EPC differentiation. Interruption of SIRT1 inhibited DDAH2, VEGF, and KDR expression, but had no effect on the level of ADMA. From our data, we concluded that DDAH2 is involved in the differentiation of EPCs and regulates the senescence and function of EPCs through the VEGF/KDR pathway by activation of SIRT1.

Statement of problem It is unknown whether dental implant systems with a platform-switched configuration have better periimplant bone stress distribution and lead to less periimplant bone level changes. Purpose The purpose of this study was to quantitatively investigate interfacial stress and stress distribution in implant bone in 2 implant abutment designs (platform-switched design and conventional diameter matching) by using a nonlinear finite element analysis method. Material and methods A finite element simulation study was applied to 2 commercially available dental implant systems: the Ankylos implant system with a reduced-diameter abutment (platform-switched implant) and the Anthogyr implant system with an abutment of the same diameter (regular platform implant). These 2 dental implant systems were positioned in a bone block, which was constructed based on a cross-sectional image of a human mandible in the molar region. In simulation, a single vertical load of 50 N, 100 N, or 150 N and horizontal loads of 50 N and 100 N were applied to the occlusal surface of the abutment. Results The finite element analysis found that the Ankylos implant system has a higher maximum von Mises stress in the implant abutment connection section and a lower maximum von Mises stress in the periimplant bone. The opposite results were found in the Anthogyr implant system. Conclusions Lower stress levels in the periimplant bone with a more uniform stress distribution were found for the Ankylos implant system with a platform-switched configuration. Although relatively higher stress was found in the abutment, premature implant failure is not anticipated because of the high strength of titanium alloy.

To investigate the expression of Abi1 in hepatocellular carcinoma (HCC) and the correlation between its expression level and clinical pathological characteristics as well as prognosis of HCC.Abi1 expression was determined at both mRNA and protein levels in 40 HCC tissues and their corresponding para carcinomatous liver tissues by RT-PCR and immunohistochemistry. The correlations between Abi1 expression levels and pathological characteristics as well as prognosis were also analyzed.The expression level of Abi1 mRNA in HCC tissues were significantly higher than those in corresponding para carcinomatous liver tissue (P0.05), and the expression level of Abi1 mRNA in nodular HCC tissues were also significantly higher than those in solitary large HCC tissues. Immunohistochemistry results showed that Abi1 protein located in cytoplasm of HCC cells and the expression level of Abi1 protein were significant positive correlated with the number of HCC, capsular formation, venous invasion and Edmondson-Steiner grade (P0.05). Combined with follow-up data, the results also showed that HCC patients with high Abi1 protein expression had a higher risk of invasion/metastasis and a shorter survival than those with low Abi1 protein expression (P0.05).Expression level of Abi1 is up-regulated in HCC tissues compared with corresponding para carcinomatous liver tissue and the expression level of Abi1 is significantly correlated with the number of tumor, capsular formation, venous invasion, Edmondson-Steiner grade and prognosis of HCC.

Tetrahydroacridine (THA), or Cognex, is currently awaiting FDA approval for the treatment of Alzheimer's disease. In addition to reports indicating that THA improves the symptoms of patients with Alzheimer's disease, we have found that THA possesses potent antiplatelet activity. THA produced dose-dependent inhibition of human platelet aggregation induced by collagen, ADP, A23187, and phorbol ester. THA, when added to activated platelets, dispersed the platelet aggregates. We have also examined the effects of THA on intracellular Ca++ mobilization, ATP release, and production of cyclic AMP.

Tetramethylpyrazine (TMPZ) is an active component that can be extracted from certain plants. In China, this herbal extract is used to treat ischemic vascular diseases. We have assessed the antithrombotic activity of TMPZ using arterial and venous thrombosis models in rats. Antithrombotic activity of TMPZ is at least partly due to its potent antiplatelet effect. We have shown that TMPZ inhibits platelet aggregation induced by ADP, collagen, thrombin, and A23187 but not by diacylglycerol (DAG). Platelets that were induced to produce maximal aggregation could be dispersed by the addition of TMPZ. Platelets could then be reaggregated by the addition of DAG. Studies monitoring intracellular ionized calcium suggest that TMPZ inhibits calcium mobilization from both the extracellular medium and from intracellular stores.

Our previous studies showed that rutaecarpine (Rut) protected against myocardial ischemia/reperfusion (I/R) injury, which was associated with activation of transient receptor potential vanilloid subtype 1 (TRPV1). Recently, TRPV1 activation was also reported to exert neuroprotective effects. The present study was to investigate the effect of Rut on hypoxia/reoxygenation (H/R)-induced apoptosis in primary rat hippocampal neurons. Three-hour hypoxia (1% O2) and consequent 24-h reoxygenation significantly increased the apoptotic death of hippocampal neurons as evidenced by increases in both TUNEL-positive cell number and caspase-3 activity. However, pretreatment with Rut (1-10microM) or caspase-3 specific inhibitor DEVD-CHO could markedly attenuate H/R-induced apoptosis in neurons. Rut markedly induced the phosphorylation of Akt and PI3K inhibitor LY294002 prevented the survival effect of Rut on neurons. Intracellular oxidative stress was significantly induced after H/R, which was inhibited by Rut and LY294002 as well as antioxidant PDTC. TRPV1 antagonist capsazepine or intracellular Ca2+ chelator BAPTA/AM could abolish these effects of Rut mentioned above. In summary, the present data suggest that Rut inhibits H/R-induced apoptosis of hippocampal neurons via TRPV1-[Ca2+]i-dependent and PI3K/Akt signaling pathway, which is related to inhibiting oxidative stress and caspase-3 activation.

Tetramethylpyrazine (TMPZ) is an active ingredient of a Chinese herbal medicine. We have previously shown that TMPZ possesses antithrombotic activity in rat thrombotic models. Inhibition of platelet aggregation and promotion of disaggregation contributed to the antithrombotic activity of TMPZ. In this study, we evaluated the antiplatelet actions of TMPZ using human platelets and found that antiplatelet activity of TMPZ included the inhibition of intracellular Ca++ mobilization (mainly the release from internal stores), the enhancement of intracellular cAMP by inhibition of phosphodiesterase activity, and the reduction of GP IIb/IIIa exposure on the surface of activated platelets.