Chemokines, a subclass of cytokine superfamily have both pro-inflammatory and migratory role and serve as chemoattractant of immune cells during the inflammatory responses ensuing spinal cord injury (SCI). The chemokines, especially CXCL-1, CXCL-9, CXCL-10 and CXCL-12 contribute significant part in the inflammatory secondary damage of SCI. Inhibiting chemokine’s activity and thereby the secondary damage cascades has been suggested as a chemokine-targeted therapeutic approach to SCI. To optimize the inhibition of secondary injury through targeted chemokine therapy, accurate knowledge about the temporal profile of these cytokines following SCI is required. Hence, the present study was planned to determine the serum levels of CXCL-1, CXCL-9, CXCL-10 and CXCL-12 at 3–6 h, 7 and 28 days and 3 m after SCI in male and female SCI patients (n = 78) and compare with age- and sex-matched patients with non-spinal cord injuries (NSCI, n = 70) and healthy volunteers (n = 100). ANOVA with Tukey post hoc analysis was used to determine the differences between the groups. The data from the present study show that the serum level of CXCL-1, CXCL-9 and CXCL-10 peaked on day 7 post-SCI and then declined to the control level. In contrast, significantly elevated level of CXCL-12 persisted for 28 days post SCI. In addition, post-SCI expression of CXCL-12 was found to be sex-dependent. Male SCI patients expressed significantly higher CXCL-12 when compared to control and SCI female. We did not observe any change in chemokines level of NSCI. Further, the age of the patients did not influence chemokines expression after SCI. These observations along with SCI-induced CSF-chemokine level should contribute to the identification of selective and temporal chemokine targeted therapy after SCI. 相似文献
Granulosa Cells (GCs) are sensitive to excessive production of reactive oxygen species (ROS). Quercetin (QUR) is a free radical scavenger which can alleviate oxidative stress through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) pathway and thioredoxin (Trx) system. We aimed to explore the probable protective role of QUR on cultured human GCs treated with hydrogen peroxide (H2O2) as an inducer of oxidative stress. MTT assay was applied for evaluating the cell cytotoxicity of QUR and H2O2. The rate of apoptotic cells and intracellular ROS generation were determined by Annexin V-FITC/PI staining and 2′-7′-dichlorodihydro?uorescein diacetate ?uorescent probes (DCFH-DA), respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blot analysis were used to evaluate the gene and protein expression of Nrf2 and kelch-like ech-associated protein 1 (Keap1)1. The Nrf2 and Trx activities were measured by Enzyme-linked Immunosorbent Assay (ELISA). The results indicated that QUR pretreatment can decrease ROS production and apoptosis induced by H2O2. In addition, QUR increased Nrf2 gene and protein expression, as well as its nuclear translocation. Moreover, in QUR-treated group, a lower level of Keap1 protein was observed, which was not reported as significant. The results also indicated a significant correlation between the expression of Nrf2 and Keap1 in QUR-treated group. Further, QUR protected GCs from oxidative stress by increasing Trx gene expression and activity. This study suggests that QUR as a supplementary factor may protect GCs from oxidative stress in diseases related to this condition. 相似文献
Sprouting angiogenesis and capillary network formation are tissue scale phenomena. There are also sub-scale phenomena involved in angiogenesis including at the cellular and intracellular (molecular) scales. In this work, a multiscale model of angiogenesis spanning intracellular, cellular, and tissue scales is developed in detail. The key events that are considered at the tissue scale are formation of closed flow path (that is called loop in this article) and blood flow initiation in the loop. At the cellular scale, growth, migration, and anastomosis of endothelial cells (ECs) are important. At the intracellular scale, cell phenotype determination as well as alteration due to blood flow is included, having pivotal roles in the model. The main feature of the model is to obtain the physical behavior of a closed loop at the tissue scale, relying on the events at the cellular and intracellular scales, and not by imposing physical behavior upon it. Results show that, when blood flow is considered in the loop, the anastomosed sprouts stabilize and elongate. By contrast, when the loop is modeled without consideration of blood flow, the loop collapses. The results obtained in this work show that proper determination of EC phenotype is the key for its survival. 相似文献
Marine oil spills are catastrophic events that cause massive damage to ecosystems at all trophic levels. While most of the research has focused on carbon-degrading microorganisms, the potential impacts of hydrocarbons on microbes responsible for nitrification have received far less attention. Nitrifiers are sensitive to hydrocarbon toxicity: ammonia-oxidizing bacteria and archaea being 100 and 1000 times more sensitive than typical heterotrophs respectively. Field studies have demonstrated the response of nitrifiers to hydrocarbons is highly variable and the loss of nitrification activity in coastal ecosystems can be restored within 1–2 years, which is much shorter than the typical recovery time of whole ecosystems (e.g., up to 20 years). Since the denitrification process is mainly driven by heterotrophs, which are more resistant to hydrocarbon toxicity than nitrifiers, the inhibition of nitrification may slow down the nitrogen turnover and increase ammonia availability, which supports the growth of oil-degrading heterotrophs and possibly various phototrophs. A better understanding of the ecological response of nitrification is paramount in predicting impacts of oil spills on the nitrogen cycle under oil spill conditions, and in improving current bioremediation practices. 相似文献
Currently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti-inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease-modifying antirheumatic drugs (DMARDs), administered as first-line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. The biological therapies, on the contrary, are chimeric anti-CD20 monoclonal antibody, rituximab, inhibitors of tumor necrosis factor-α (TNF-α) like etanercept, infliximab, and adalimumab, a recombinant inhibitor of interleukin-1 (IL-1), anakinra, and costimulation blocker, abatacept. Moreover, newly under evaluation biological therapies include new TNF-α inhibitors, JAK inhibitors, anti-interleukin-6-receptor monoclonal antibodies (mABs), and antibodies against vital molecules involved in the survival and development of functional B cells. The new strategies to treat RA has improved the course of the disease and most of the patients are successful in remission of the clinical manifestations if the diagnosis of the disease occur early. The probability of remission increase if the diagnosis happens rapidly and treat-to-target approach are implemented. In this review article, we have attempted to go through the treatment strategies for RA therapy both the routine ones and those which have been developed over the past few years and currently under investigation. 相似文献
Plant Cell, Tissue and Organ Culture (PCTOC) - Methyl chavicol and methyl eugenol are important phenylpropanoid compounds previously purified from basil. These compounds are significantly enhanced... 相似文献
Fuel economy and emissions of heavy-duty trucks greatly vary based on vehicular/environmental conditions. Large-scale infrastructure construction projects require a large amount of material/equipment transportation. Single-parameter generic hauling models may not be the best option for an accurate estimation of hauling contribution in life cycle assessment (LCA) involving construction projects; therefore, more precise data and parameterized models are required to represent this contribution. This paper discusses key environmental/operational variables and their impact on transportation of materials and equipment; a variable-impact transportation (VIT) model accounting for these variables was developed to predict environmental impacts of hauling.
Methods
The VIT model in the form of multi-nonlinear regression equations was developed based on simulations using the U.S. Environmental Protection Agency (EPA)’s Motor Vehicle Emission Simulator (MOVES) to compute all the impact categories in EPA’s TRACI 2.1 and energy consumption of transportation. Considering actual driving cycles of hauling trucks recorded during a pavement rehabilitation project, the corresponding environmental impacts were calculated, and sensitivity analyses were performed. In addition, an LCA case study based on historical pavement reconstruction projects in Illinois was conducted to analyze the contribution of transportation and variability of its impacts during the pavements’ life cycle.
Results and discussion
The importance of vehicle driving cycles was realized from simulation results. The case study results showed that considering driving cycles using the VIT model could increase the contribution of hauling in total life cycle Global Warming Potential (GWP) and total life cycle GWP itself by 2–4 and 3–5%, respectively. In addition to GWP, ranges of other hauling-related impact categories including Smog, Ozone Depletion, Acidification, and Primary Energy Demand from fuel were presented based on the case study. Ozone Depletion ranged from 9 to 45%, and Smog ranged from 11 to 48% of the total relevant life cycle impacts. The GWP contribution of hauling in pavement LCA ranged between 5 and 32%. The results indicate that the contribution of hauling transportation can be significant in pavement LCA.
Conclusions
For large-scale roadway infrastructure construction projects that need a massive amount of material transportation, high fidelity models and data should be used especially for comparative LCAs that can be used as part of decision making between alternatives. The VIT model provides a simple analytical platform to include the critical vehicular/operational variables without any dependence on an external software; the model can also be incorporated in those studies where some of the transportation activity data are available.
New-generation wide-base tire (NG-WBT) is known for improving fuel economy and at the same time for potentially causing a greater damage to pavement. No study has been conducted to evaluate the net environmental saving of the combined system of pavements and NG-WBT. This study adopted a holistic approach (life cycle assessment [LCA] and life cycle costing [LCC]) to quantitatively evaluate the environmental and economic impact of using NG-WBT.
Methods
The net effect of different levels of market penetration of NG-WBT on energy consumption, global warming potential (GWP), and cost based on the fatigue cracking and rutting performance of two different asphalt concrete (AC) pavement structures was evaluated. The performance of pavements was determined based on pavement design lives; pavement surface characteristics, and pavement critical strain responses obtained from the artificial neural network (ANN) based on finite element (FE) simulations were used to calculate design lives of pavements. Based on the calculated design lives, life cycle inventory (LCI) and cost databases, and rolling resistance (RR) models previously developed by the University of Illinois at Urbana-Champaign (UIUC) were used to calculate the environmental and economic impact of the combined system.
Results and discussion
The fuel economy improvement using NG-WBT is 1.5% per axle. Scenario-based case studies were conducted. Considering 0% NG-WBT market penetration (or 100% standard dual tire assembly [DTA]) as a baseline, scenario 1 assumed the same fatigue and rutting potential between NG-WBT and DTA; therefore, the only difference came from fuel economy improvement of using NG-WBT. In scenario 2, pavement fatigue cracking potential determined the pavement design life; both thick and thin AC overlay sections experienced positive net environmental savings, but mixed net economic savings. In scenario 3, pavement rutting potential determined the pavement design life; the thick AC overlay section experienced positive net environmental savings, but mixed net economic savings. The thin section experienced negative net environmental and economic savings.
Conclusions
The outcomes of scenario-based case studies indicated that NG-WBT can result in significant savings in life cycle energy consumption and cost, and GWP; however, these benefits were sensitive to the method used to determine the pavement performance; especially, a small change in pavement strain can result in significant change in pavement life. In addition, the effect of fuel price/economy improvement, discount rate, and International Roughness Index (IRI) threshold values was studied in the sensitivity analyses.
