Dimethyl fumarate protects thioacetamide‐induced liver damage in rats: Studies on Nrf2, NLRP3, and NF‐κB

The present study was designed to investigate the hepatoprotective potential of dimethyl fumarate (DMF) against thioacetamide (TAA)‐induced liver damage. Wistar rats were treated with DMF (12.5, 25, and 50 mg/kg/day, orally) and TAA (200 mg/kg intraperitoneally, every third day) for 6 consecutive weeks. TAA exposure significantly reduced body weight, increased liver weight and index, and intervention with DMF did not ameliorate these parameters. DMF treatment significantly restored TAA‐induced increase in the levels of aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transferase, total bilirubin, uric acid, malondialdehyde, reduced glutathione, and histopathological findings such as inflammatory cell infiltration, deposition of collagen, necrosis, and bridging fibrosis. DMF treatment significantly ameliorated TAA‐induced hepatic stellate cell activation, increase in inflammatory cascade markers (NACHT, LRR, and PYD domains‐containing protein 3; NLRP3, apoptosis‐associated speck like protein containing a caspase recruitment domain; ASC, caspase‐1, nuclear factor‐kappa B; NF‐κB, interleukin‐6), fibrogenic makers (α‐smooth muscle actin; ɑ‐SMA, transforming growth factor; TGF‐β1, fibronectin, collagen 1) and antioxidant markers (nuclear factor (erythroid‐derived 2)‐like factor 2; Nrf2, superoxide dismutase‐1; SOD‐1, catalase). The present findings concluded that DMF protects against TAA‐induced hepatic damage mediated through the downregulation of inflammatory cascades and upregulation of antioxidant status.     

Circular RNA ciRS‐7 promotes tube formation in microvascular endothelial cells through downregulation of miR‐26a‐5p

Atherosclerosis is one of the most common and crucial heart diseases involving the heart and brain. At present, atherosclerosis and its major complications comprise the leading causes of death worldwide. Our purpose was to identify the role of ciRS‐7 in atherosclerosis. Tubulogenesis of HMEC‐1 cell was evaluated utilizing tube formation assay. Cell Counting Kit‐8 assay and flow cytometry were utilized to test viability and apoptosis. Migration assay was utilized to determine the migration capacity of experimental cells. Western blot was applied to examine apoptosis and tube formation‐associated protein expression. In addition, the above experiments were repeated when silencing ciRS‐7, overexpressing ciRS‐7, and upregulating miR‐26a‐5p. HMEC‐1 cells formed tube‐like structures over time. Silencing ciRS‐7 suppressed viability, migration, and tube formation but promoted apoptosis. Oppositely, overexpressing ciRS‐7 reversed the effect in HMEC‐1 cells. miR‐26a‐5p expression was elevated by silencing ciRS‐7 and reduced by overexpressing ciRS‐7. Moreover, overexpressing ciRS‐7 facilitated viability, migration, and tube formation via upregulating miR‐26a‐5p. Conclusively, overexpressing ciRS‐7 mobilized phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway and suppressed c‐Jun N‐terminal kinase (JNK)/p38 pathway. ciRS‐7 exerted influence on apoptosis, viability, migration, and tube formation through mediating PI3K/AKT and JNK/p38 pathways by miR‐26a‐5p downregulation in HMEC‐1 cells.     

MiR‐16, as a potential NF‐κB‐related miRNA,exerts anti‐inflammatory effects on LPS‐induced myocarditis via mediating CD40 expression: A preliminary study

The purpose of this study was to investigate the biological effect of miR‐16 on myocarditis and the underlying molecular mechanism. H9c2 cells were treated with 10 µg/mL lipopolysaccharide (LPS) for 12 hours to form a myocarditis injury model. We observed that LPS treatment distinctly decreased the level of miR‐16 in H9c2 cells. Upregulation of miR‐16 increased cell proliferation and reduced cell apoptosis. Then, CD40 was predicted and verified as a target gene of miR‐16 by TargetScan and luciferase reporter assay, respectively. Furthermore, the messenger RNA and protein expression of CD40 are negatively regulated by miR‐16. The relative expression of inflammatory factors was dramatically decreased by the miR‐16 mimic. Cells cotransfected with miR‐16 mimic and si‐CD40 could significantly abolish the injury of cardiomyocytes caused by myocarditis. Our study illustrated that the upregulation of miR‐16 has a protective effect on LPS‐damaged H9c2 cells, which may be achieved by regulating CD40 and the nuclear factor kappa B pathway.     

Galectin‐3 mediates pulmonary vascular endothelial cell dynamics via TRPC1/4 under acute hypoxia

Galectin‐3 (Gal‐3) has been implicated in various biological functions, yet little is known about its role in regulating the dynamics of pulmonary vascular endothelial cells. Gal‐3 was shown to be increased in hypoxic model rats by sequencing analysis. We exposed pulmonary vessel endothelial cells (PVECs) to hypoxia or Gal‐3 stimulation, following which cell apoptosis and autophagy were measured with the relevant methods. The results demonstrated that hypoxia elevated nuclear factor‐κB (NF‐κB) activity and Gal‐3 expression. Gla‐3 decreased the expression of Bcl‐2, Alix, Beclin‐1, Atg5, and LC3A/B. The messenger RNA and protein levels of transient receptor potential channel 1/4 (TRPC1/4) and calpain were reduced after Gal‐3 treatment. Gal‐3 also activated protein kinase B/glycogen synthase kinase‐3 β/mammalian target of rapamycin signaling pathways in PVECs. These results suggest that a hypoxia‐mediated increase in Gal‐3 promotes apoptosis and inhibits autophagy by inhibiting the TRPC1/4 pathway and activating the protein kinase B/glycogen synthase kinase‐3 β/mammalian target of rapamycin signaling pathway in PVECs. Furthermore, these results may provide us with a new direction to explore the pathogenesis of pulmonary artery hypertension.     

Deleterious cardiovascular effect of exosome in digitalis‐treated decompensated congestive heart failure

Heart failure (HF) is a medical condition inability of the heart to pump sufficient blood to meet the metabolic demand of the body to take place. The number of hospitalized patients with cardiovascular diseases is estimated to be more than 1 million each year, of which 80% to 90% of patients ultimately progress to decompensated HF. Digitalis glycosides exert modest inotropic actions when administered to patients with decompensated HF. Although its efficacy in patients with HF and atrial fibrillation is clear, its value in patients with HF and sinus rhythm has often been questioned. A series of recent studies have cast serious doubt on the benefit of digoxin when added to contemporary HF treatment. We are hypothesizing the role and mechanism of exosome and its biological constituents responsible for worsening the disease state and mortality in decompensated HF patients on digitalis.     

Climate change impacts on asphalt road pavement construction and maintenance: An economic life cycle assessment of adaptation measures in the State of Virginia,United States

Pavement design and management practices must be adapted in response to future climate change. While many studies have attempted to identify different methods to adapt pavements to future climate conditions, the potential economic impacts of the adaptations still remain largely unquantified. This study presents the results of a comprehensive life‐cycle cost analysis (LCCA) aimed at quantifying the potential economic impacts of a climate adaptation method, in which an upgraded asphalt binder (Performance Grade PG 76‐22) is used in the construction and maintenance of flexible pavement sections in lieu of the original binder (PG 70‐22) for improved resistance against high temperatures. For each of three major Virginia Department of Transportation (VDOT) districts with different climates, three case studies consisting of typical interstate, primary, and secondary pavement sections were considered. The LCCA accounted for the costs incurred during the mixture's production, maintenance, and use phases of the pavement life cycle by explicitly considering future climate projections, pavement life‐cycle performance, maintenance effects, and work zone user delays. The study concludes that pavements using the upgraded binder not only perform better over time but are also economically advantageous compared to those with the original binder under the conditions of the anticipated future climate conditions (2020–2039).     

Technoecological analysis of energy carriers for long‐haul transportation

Long‐haul transportation demand is predicted to increase in the future, resulting in higher carbon dioxide emissions. Different drivetrain technologies, such as hybrid or battery electric vehicles, electrified roads, liquefied natural gas and hydrogen, might offer solutions to this problem. To assess their ecological and economic impact, these concepts were simulated including a weight and cost model to estimate the total cost of ownership. An evolutionary algorithm optimizes each vehicle to find a concept specific optimal solution. A model calculates the minimum investment in infrastructure required to meet the energy demand for each concept. A well‐to‐wheel analysis takes into account upstream and on‐road carbon dioxide emissions, to compare fully electric vehicles with conventional combustion engines. Investment in new infrastructure is the biggest drawback of electrified road concepts, although they offer low CO₂ emissions. The diesel hybrid is the best compromise between carbon reduction and costs.     

Lifting the veil on the correction of double counting incidents in hybrid life cycle assessment

Life cycle assessment (LCA) and environmentally extended input–output analyses (EEIOA) are two techniques commonly used to assess environmental impacts of an activity/product. Their strengths and weaknesses are complementary, and they are thus regularly combined to obtain hybrid LCAs. A number of approaches in hybrid LCA exist, which leads to different results. One of the differences is the method used to ensure that mixed LCA and EEIOA data do not overlap, which is referred to as correction for double counting. This aspect of hybrid LCA is often ignored in reports of hybrid assessments and no comprehensive study has been carried out on it. This article strives to list, compare, and analyze the different existing methods for the correction of double counting. We first harmonize the definitions of the existing correction methods and express them in a common notation, before introducing a streamlined variant. We then compare their respective assumptions and limitations. We discuss the loss of specific information regarding the studied activity/product and the loss of coherent financial representation caused by some of the correction methods. This analysis clarifies which techniques are most applicable to different tasks, from hybridizing individual LCA processes to integrating complete databases. We finally conclude by giving recommendations for future hybrid analyses.     

Eco‐efficiency assessment of calcium sulfoaluminate clinker production

Calcium sulfoaluminate‐based cements (CSA) are proposed as a cement alternative with a low carbon footprint. The nature of CSA makes the manufacturing process to require lower temperature, less fuel, and less calcite. However, it requires aluminum oxide, Al₂O₃, which would be originated from bauxite and bauxite‐derived wastes, and sulfur, coming from calcium sulfate or elemental sulfur. An eco‐efficiency assessment of CSA cements, benchmarked against the conventional Portland cement, has been performed following the principles of ISO 14045 on eco‐efficiency for a total of 240 CSA clinker production scenarios. The eco‐efficiency indicator relates an environmental indicator with a product system value indicator, and it is calculated for each of the studied parameters: bauxite geographical origin, the fuel used for clinkering, the source of sulfur, and the composition of the clinker. Eco‐efficiency results show a strong dependence on the origin of bauxite, while other parameters, as the fuel used, its content in sulfur, or the supply of other raw materials, are of less importance. The most eco‐efficient solutions are those with certain closeness to bauxite sources. To achieve global solutions, that is, cement‐making based on CSA independently of the origin of the raw materials, the amount of bauxite needs to be minimized and CSA composition restricted.