Andrographolide alleviates paraquat-induced acute lung injury by activating the Nrf2/HO-1 pathway

Objective(s): Paraquat (PQ), a highly effective and rapidly non-selective herbicide, mainly targets the lungs and causes acute lung injury (ALI). So far, the scarcity of effective drug candidates against PQ-induced ALI remains a big challenge. Andrographolide (Andro), with its anti-inflammatory and antioxidant activities, has been demonstrated to alleviate ALI. Nevertheless, whether Andro could alleviate the PQ-mediated ALI remains unknown. Therefore, this study will explore the effects as well as the possible mechanism of Andro against ALI caused by PQ. Materials and Methods: C57BL/6J mice were injected with 20 mg/kg PQ intraperitoneally to establish an ALI model. PQ-treated MLE-12 cells were applied to a vitro model. Nuclear factor erythroid like-2 (Nrf2) was knocked out to explore the specific effects of the Nrf2/ Heme oxygenase-1 (OH-1) pathway in the protection of Andro against ALI caused by PQ.Results: Andro significantly reduced lung damage and the ratio of Wet/Dry (W/D) weight, decreased MDA, IL-6, IL-1β, and TNF-ɑ levels, reversed the decrease of CAT and SOD levels, and inhibited apoptosis caused by PQ. Andro obviously increased the ratio of Bcl-2/Bax while reducing caspase-3 and cleaved caspase-3 levels. Furthermore, Andro dramatically elevated the antioxidant proteins Nrf2, NQO-1, and HO-1 levels compared with the PQ group. This experiment demonstrated that Andro reduced ROS and inhibited apoptosis, induced by PQ in MLE-12 cells, by inducing Nrf2/HO-1 pathway activation.Conclusion: Andro effectively ameliorates oxidant stress and apoptosis in ALI caused by PQ, possibly through inducing Nrf2/HO-1 pathway activation

How Well Does the ERA5 Reanalysis Capture the Extreme Climate Events Over China? Part II: Extreme Temperature

The fifth-generation atmospheric reanalysis of the European Center for Medium-Range Weather Forecasts (ERA5) is the latest reanalysis product. However, the reliability of ERA5 to capture extreme temperatures is still unclear over China. Hence, based on conventional meteorological station data, a new criterion (DISO) was used to validate the ERA5 capturing extreme temperature indices derived from the Expert Team on Climate Change Detection and Indices (ETCCDI) across the six subregions of China on different timescales. The conclusions are as follows: the original daily temperatures (mean temperature, maximum temperature, and minimum temperature) can be well reproduced by ERA5 reanalysis over China. ERA5 tends to exhibit more misdetection for the duration of extreme temperature events than extreme temperature intensity and frequency. In addition, ERA5 performed best in the summer and worst in the winter, respectively. The trend of absolute indices (e.g., TXx and TNx), percentile-based indices (e.g., TX90p, TX10p, TN90p, and TN10p), and duration indices (e.g., WSDI, CSDI, and GSL) can be captured by ERA5, but ERA5 failed to capture the tendency of the diurnal temperature range (DTR) over China. Spatially, ERA5 performs well in southeastern China. However, it remains challenging to accurately recreate the extreme temperature events in the Tibetan Plateau. The elevation difference between the station and ERA5 grid point contributes to the main bias of reanalysis temperatures. The accuracy of ERA5 decreases with the increase in elevation discrepancy

How Well Does the ERA5 Reanalysis Capture the Extreme Climate Events Over China? Part I: Extreme Precipitation

ERA5 is the fifth-generation atmospheric reanalysis of the European Center for Medium-Range Weather Forecasts, with high spatiotemporal resolution and global coverage. However, the reliability of ERA5 for simulating extreme precipitation events is still unclear over China. In this study, 12 extreme precipitation indices and a comprehensive quantitative distance between indices of simulation and observation were used to evaluate ERA5 precipitation from three fundamental aspects: intensity, frequency, and duration. The geomorphological regionalization method was used to divide the subregions of China. The results showed that the ability of ERA5 to simulate annual total precipitation was better than that of daily precipitation. For the intensity indices, ERA5 performs well for simulating the PRCPTOT (annual total wet days precipitation) over China. ERA5 performs better on RX5day (max 5-days precipitation amount) and R95p (very wet days), especially in eastern China, than on RX1day (max 1-day precipitation amount) and R99p (extremely wet days). For the frequency indices, the ability of the ERA5 simulation increased as the amount of precipitation increased, except for northwestern China. However, the ability of ERA5 to simulate R50 mm (number of extreme heavy precipitation days) decreased. For the duration indices, ERA5 was better at simulating drought events than wet events in eastern China. Our results highlight the need for ERA5 to enhance the simulation of trend changes in extreme precipitation events

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA

Biomedical Simulator Using Nonlinear Finite Element Modeling of the Human Head

Biomaterials, including brain tissue, usually have nonlinear material properties. In this project, a human head simulator using the finite element method (FEM) was improved by adding an implementation of a nonlinear material model into it. The Ogden model is chosen to be implemented in this project because of its good accuracy to model the brain tissue. This work aims at improving the validity of impact simulation tests. Results show that the nonlinear model was successfully implemented into the simulator and a difference was discovered when conducting impact simulation. In the simulation using a nonlinear model, the deformation of brain tissue is larger than the deformation using a linear model

Biomedical Simulator Using Nonlinear Finite Element Modeling of the Human Head

Biomaterials, including brain tissue, usually have nonlinear material properties. In this project, a human head simulator using the finite element method (FEM) was improved by adding an implementation of a nonlinear material model into it. The Ogden model is chosen to be implemented in this project because of its good accuracy to model the brain tissue. This work aims at improving the validity of impact simulation tests. Results show that the nonlinear model was successfully implemented into the simulator and a difference was discovered when conducting impact simulation. In the simulation using a nonlinear model, the deformation of brain tissue is larger than the deformation using a linear model

Andrographolide alleviates paraquat-induced acute lung injury by activating the Nrf2/HO-1 pathway.

OBJECTIVES: Paraquat (PQ), a highly effective and rapidly non-selective herbicide, mainly targets the lungs and causes acute lung injury (ALI). So far, the scarcity of effective drug candidates against PQ-induced ALI remains a big challenge. Andrographolide (Andro), with its anti-inflammatory and antioxidant activities, has been demonstrated to alleviate ALI. Nevertheless, whether Andro could alleviate the PQ-mediated ALI remains unknown. Therefore, this study will explore the effects as well as the possible mechanism of Andro against ALI caused by PQ. MATERIALS AND METHODS: C57BL/6J mice were injected with 20 mg/kg PQ intraperitoneally to establish an ALI model. PQ-treated MLE-12 cells were applied to a vitro model. Nuclear factor erythroid like-2 (Nrf2) was knocked out to explore the specific effects of the Nrf2/ Heme oxygenase-1 (OH-1) pathway in the protection of Andro against ALI caused by PQ. RESULTS: Andro significantly reduced lung damage and the ratio of Wet/Dry (W/D) weight, decreased MDA, IL-6, IL-1β, and TNF-ɑ levels, reversed the decrease of CAT and SOD levels, and inhibited apoptosis caused by PQ. Andro obviously increased the ratio of Bcl-2/Bax while reducing caspase-3 and cleaved caspase-3 levels. Furthermore, Andro dramatically elevated the antioxidant proteins Nrf2, NQO-1, and HO-1 levels compared with the PQ group. This experiment demonstrated that Andro reduced ROS and inhibited apoptosis, induced by PQ in MLE-12 cells, by inducing Nrf2/HO-1 pathway activation. CONCLUSION: Andro effectively ameliorates oxidant stress and apoptosis in ALI caused by PQ, possibly through inducing Nrf2/HO-1 pathway activation

Linear Dextrin as Potential Insulin Delivery System: Effect of Degree of Polymerization on the Physicochemical Properties of Linear Dextrin–Insulin Inclusion Complexes

In the current study, linear dextrin (LD) was prepared using waxy potato starch debranched with pullulanase, which has attracted immense interest in the food, pharmaceutical, and cosmetic industries as a versatile ingredient. Various LDs were separated on the basis of their differential solubility in aqueous/ethanol solutions of different volumetric ratios. Three LD products—LD Fabrications with 40% ethanol (F-40); LD Fabrications with 50% ethanol (F-50); and LD Fabrications with 60%, 70%, and 80% ethanol (F-M)—were obtained with an average degree of polymerization (DP) values of 31.44, 21.84, and 16.10, respectively. The results of Fourier transform infrared spectroscopy (FT-IR) analysis revealed that the reaction mainly involved hydrogen bonding and a hydrophobic interaction between LD and insulin in the process of inclusion complex formation. X-ray diffraction (XRD) results indicated that insulin was encapsulated in LD. The results of circular dichroism (CD) showed that the changes in the secondary structure of insulin were negligible during the release from the inclusion complexes. The order of encapsulation capacity is as follows: the complex composed of F-M and insulin (F-M-INS) > the complex composed of LD and insulin (LD-INS) > the complex composed of F-50 and insulin (F-50-INS) > and the complex composed of F-40 and insulin (F-40-INS). F-M-INS inclusion complexes showed a better effect on reducing the release of insulin in gastric juice and promoting the release of insulin in intestinal juice and blood plasma than LD-INS

Enhanced In Vitro Cascade Catalysis of Glycerol into Pyruvate and Acetoin by Integration with Dihydroxy Acid Dehydratase from Paralcaligenes ureilyticus

Recently, an in vitro enzymatic cascade was constructed to transform glycerol into the high-value platform chemical pyruvate. However, the low activity of dihydroxy acid dehydratase from Sulfolobus solfataricus (SsDHAD) limited the efficiency. In this study, the enzymatic reduction of pyruvate catalyzed by d-lactate dehydrogenase from Pseudomonas aeruginosa PAO1 was used to assay the activities of dihydroxy acid dehydratases. Dihydroxy acid dehydratase from Paralcaligenes ureilyticus (PuDHT) was identified as the most efficient candidate for glycerate dehydration. After the optimization of the catalytic temperature for the enzymatic cascade, comprising alditol oxidase from Streptomyces coelicolor A3, PuDHT, and catalase from Aspergillus niger, 20.50 ± 0.27 mM of glycerol was consumed in 4 h to produce 18.95 ± 0.97 mM of pyruvate with a productivity 12.15-fold higher than the previous report using SsDHAD. The enzymatic cascade was further coupled with the pyruvate decarboxylase from Zymomonas mobile for the production of another platform compound, acetoin. Acetoin at a concentration of 8.52 ± 0.12 mM was produced from 21.62 ± 0.19 mM of glycerol with a productivity of 1.42 ± 0.02 mM h−1