cFLIPL Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting Endoplasmic Reticulum Stress.

PURPOSE: Endoplasmic reticulum stress (ERS) plays a crucial role in myocardial ischemia-reperfusion injury (MIRI). Cellular FLICE-inhibitory protein (cFLIP) is an essential regulator of apoptosis and plays a major role in regulating ERS. The present study aimed to investigate the effects of long isoform cFLIP (cFLIPL) on endogenous apoptosis and the mechanism of ERS in MIRI. METHODS: The cFLIPL recombinant adenovirus vector was used to infect H9c2 cells and Sprague-Dawley (SD) rats. After infection for 72 h, ischemia was induced for 30 min, and reperfusion was then performed for 2 h to establish the MIRI model in SD rats. H9c2 cells were hypoxic for 4 h and then reoxygenated for 12 h to simulate ischemia/reperfusion (I/R) injury. Model parameters were evaluated by assessing cardiomyocyte viability, cell death (apoptosis), and ERS-related protein expression. In addition, tunicamycin (TM), an ERS agonist, was also added to the medium for pretreatment. Coimmunoprecipitation (Co-IP) of cFLIPL and p38 MAPK protein was performed. RESULTS: cFLIPL expression was decreased in I/R injury and hypoxia/reoxygenation (H/R) injury, and cFLIPL overexpression reduced myocardial infarction in vivo and increased the viability of H9c2 cells in vitro. I/R and H/R upregulated the protein expression of GRP78, IRE-1, and PERK to induce ERS and apoptosis. Interestingly, overexpression of cFLIPL significantly inhibited ERS and subsequent apoptosis, which was reversed by an agonist of ERS. Moreover, Co-IP showed that cFLIPL attenuated ERS and was associated with inhibiting the activation of p38 protein. CONCLUSION: The expression of cFLIPL is significantly downregulated in MIRI, and it is accompanied by excessive ERS and apoptosis. Upregulated cFLIPL suppresses ERS to reduce myocardial apoptosis, which is associated with inhibiting the activity of p38 MAPK. Therefore, cFLIPL may be a potential intervention target for MIRI.

Research Progress on The Mechanism and Treatment of Inflammatory Response in Myocardial Ischemia-Reperfusion Injury.

Acute myocardial infarction can be treated aggressively with intravenous thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting; however, recanalization can cause myocardial ischemia-reperfusion injury (MIRI). This is an important reason that restricts the treatment effect of patients. After the ischemic myocardium is restored to perfusion, an inflammatory response can occur within minutes and peak within a few days. Many pro-inflammatory cytokines can seriously damage cardiac function. Inflammation can regulate cardiomyocyte apoptosis, autophagy, pyroptosis, and necrosis, and is the main initiating factor leading to MIRI in cardiomyocytes. This article reviews the mechanism of inflammatory response in the ischemia-reperfusion period after acute myocardial infarction and the clinical value and application prospect of inhibiting inflammatory response in the treatment of acute myocardial infarction.

Cellular FADD-like IL-1ß-converting enzyme-inhibitory protein attenuates myocardial ischemia/reperfusion injury via suppressing apoptosis and autophagy simultaneously.

BACKGROUND AND AIMS: Myocardial ischemia/reperfusion injury (MI/RI) is a result of coronary revascularization, and often increases cell apoptosis and autophagy. Downregulated cellular FADD-like-IL-1ß-converting enzyme-inhibitory protein (cFLIP) was associated with development of several myocardial diseases, whether overexpression of cFLIP can attenuate MI/RI remains unclear. This study aimed to determine the effects of cFLIP on apoptosis and autophagy in MI/RI. METHODS AND RESULTS: Ischemia/reperfusion (I/R) rat model and hypoxia/reoxygenation (H/R) cardiomyocytes model were established. Both I/R injury and H/R injury down-regulated expression of two cFLIP isoforms (cFLIPL and cFLIPS), and instigated apoptosis and autophagy simultaneously. Overexpression of cFLIPL and/or cFLIPS led to a significant increase in cardiomyocytes viability in vitro, and also reduced the myocardial infarct volume in vivo, these changes were associated with suppressed apoptosis and autophagy. Mechanistically, overexpression of cFLIP significantly downregulated pro-apoptotic molecules (Caspase-3, -8, -9), and pro-autophagic molecules (Beclin-1 and LC3-II). Moreover, cFLIP significantly suppressed activity of NF-κB pathway to upregulate the expression of Bcl-2, which is the molecular of interplay of apoptosis and autophagy. CONCLUSION: Overexpression of cFLIP significantly attenuated MI/RI both in vivo and vitro via suppression of apoptosis and lethal autophagy. cFLIP can suppress activity of NF-κB pathway, and further upregulated expression of Bcl-2.

Duration of dual antiplatelet therapy after percutaneous coronary intervention with implantation of second-generation drug-eluting stent: A meta-analysis of randomized controlled trials.

Objective: The optimal duration of dual antiplatelet therapy (DAPT) in patients after PCI with implantation of a drugeluting stent is still controversial. We conducted a meta-analysis to compare the efficacy and safety of short term DAPT (≤ 3 months) followed by P2Y12 inhibitor monotherapy and standard DAPT (12 months) after PCI. Method: Relevant studies published in Medline, Embase, CoChrane Library were searched for randomized controlled trials (RCTs) until November 2019. Studies were screened by selection criteria then quality assessed through the Cochrane Collaboration's tool. Data were extracted from the included studies and statistically analyzed by RevMan 5.3 software. Results: Five RCTs (n=18,357) were included. Compared with standard DAPT, the short term DAPT was associated with a significant decrease in the major bleeding [odds ratio (OR)=0.43, 95% Confidence Interval (CI):0.32-0.58, P <0.00001] and any bleeding [OR=0.56, 95%CI:0.47-0.66, P<0.00001]. There were no significant differences in all-cause death [OR=0.91, 95%CI:0.71-1.16, P =0.45], major adverse cardiac and cerebrovascular event [OR=1.01, 95%CI:0.87-1.17, P =0.91] and stent thrombosis [OR=0.97, 95%CI:0.61-1.54, P =0.91] between with the short term DAPT group and the standard DAPT group. Conclusions: Short term DAPT followed by P2Y12 monotherapy could reduce the risk of bleeding without increasing the incidence of ischemic events after PCI with implantation of second-generation DES compared with standard DAPT. Therefore, short term DAPT may be a promising strategy to balance ischemic events and bleeding complications in patients after PCI.

Effects of fresh-salt water interaction on spatial variations of soil organic carbon in reed wetland of Yellow River Estuary.

Estuarine wetlands exhibit significant interaction between fresh and salt water, with long-term carbon sequestration capability. We set up 60 sampling sites in the reed wetlands of the fresh-salt water interaction zone of the Yellow River Estuary, covering four different zones of the weak-intensity fresh-salt water interaction zone (WIZ), medium-intensity fresh-salt water interaction zone (MIZ), high-intensity interaction fresh-salt water zone (HIZ) and strong-intensity fresh-salt water interaction zone (SIZ). We investigated how fresh-salt water interaction affected the spatial variation of soil organic carbon (SOC) storage. The results showed that the area of reed wetland accounted for 17.8% of the total area of the fresh-salt water interaction zone the Yellow River Estuary, which mainly distributed in the WIZ and MIZ. The SOC content of reed wetland in the fresh-salt water interaction zone ranged from 1.09 to 3.65 g·kg-1, the SOC density was between 1.85-5.84 kg·m-2, and the SOC storage was (17.32±3.64)×104 t. The SOC content and SOC density decreased with increasing fresh-salt water interaction. There were significant differences in surface SOC content between different subzones of the fresh-salt water interaction zone. The surface SOC content decreased significantly with the increases of fresh-salt water interaction intensity. SOC density was positively correlated with SOC, TN, NH4+-N, and biomass, but negatively correlated with salt ions, soil bulk density, pH, and EC. SOC storage in the 0-30 cm soil layer accounted for 50.9%-64.2% of that in the 0-60 cm soil layer, while SOC storage in the 0-60 cm soil layer occupied 19.1%-37.7% of that in the 0-400 cm soil layer. The results could provide a scientific basis for accurately evaluating SOC storage of estuarine wetlands, improving carbon sink function and wetland management.

[Effects of Water-salt Environment on Freshwater Wetland Soil C, N, and P Ecological Stoichiometric Characteristics in the Yellow River Estuary Wetland].

Carbon (C), nitrogen (N), and phosphorus (P) are important nutrients, and their ecological stoichiometric characteristics can reflect the quality and fertility capacity of soil, which is critical to understanding the stable mechanisms of estuarine wetland ecosystems. Under global changes, the increase in salinity and flooding caused by sea level rise will lead to changes in biogeochemical processes in estuarine wetlands, which is expected to affect the ecological stoichiometric characteristics of soil C, N, and P and ultimately interfere with the stability of wetland ecosystems. However, it remains unclear how the C, N, and P ecological stoichiometric characteristics respond to the water-salt environment in estuarine wetlands. We differentiated changes in the C, N, and P ecological stoichiometric characteristics through an ex-situ culture experiment for 23 months in the Yellow River Estuary Wetland. The five sites with distinct tidal hydrology were selected to manipulate translocation of soil cores from the freshwater marsh to high-, middle-, and low-tidal flats in June 2019. The results showed that soil water content (SWC); electrical conductivity (EC); and C, N, and P ecological stoichiometric characteristics of freshwater marsh soil significantly changed after translocation for 23 months. SWC decreased on the high- and middle-tidal flats (P<0.05) and increased on the low-tidal flat (P<0.05). EC increased to different degrees on all three tidal flats (P<0.05). Soil total organic carbon (TOC) and total nitrogen (TN) were significantly lower on the high-tidal flat (P<0.05), whereas total phosphorus (TP) was significantly lower on the middle- and high-tidal flats (P<0.05). C:N was decreased on the high- and middle-tidal flats (P<0.05); C:P and N:P were lower on the high-tidal flat; and all C, N, and P ecological stoichiometric characteristics showed no change on the low-tidal flat (P>0.05). Pearson's analysis showed that the ecological stoichiometric characteristics of C, N, and P were related to some properties of soil over the culture sites. The PLS-SEM model showed that the water-salt environment had different effects on soil C:N, C:P, and N:P through the main pathways of negative effects on soil TOC and TP. The results suggest that sea level rise may impact the C, N, and P ecological stoichiometric characteristics in freshwater marsh soil, resulting in some possible changes in the nutrient cycles of estuarine wetlands.

[Spatial Distribution and Eco-stoichiometric Characteristics of Soil Nutrient Elements Under Different Vegetation Types in the Yellow River Delta Wetland].

To clarify the distribution characteristics and the ecological stoichiometric characteristics of nutrient elements in soils under different vegetation types, four typical natural wetlands, i.e., Phragmites australis wetland, Tamarix chinensis wetland, Suaeda salsa wetland, and Tidal flat wetland, as well as Gossypium spp. fields that were reclaimed from natural wetlands, were selected as study sites in the Yellow River Delta, and comparisons between the agricultural reclamation land and natural wetlands were conducted. The results showed that the soil total organic carbon (TOC) and total nitrogen (TN) contents in the natural wetlands were as follows:P. australis wetland and T. chinensis wetland>S. salsa wetland>Tidal flat, and the contents of TOC and TN were significantly negatively related to electrical conductivity (EC) and pH values (P<0.05). The contents of TOC, TN, and total phosphorus (TP) in Gossypium spp. fields were significantly higher than those in natural wetlands (P<0.05), especially the contents of nitrate nitrogen (NO3--N) in Gossypium spp. fields, which were 9.4-11.4 times that of natural wetlands. However, no significant correlations between TOC, TN, and TP and EC and pH values (P>0.05) were observed in Gossypium spp. fields. The results of correlation analysis showed that the C/N of natural wetlands were mainly controlled by the contents of TN (P<0.05), and the C/N of the Gossypium spp. fields were significantly lower than those of natural wetlands (P<0.05). The soil C/P and N/P of natural wetlands and Gossypium spp. fields in the Yellow River Delta were low, and the variation trends were consistent with those of soil TOC and TN. Comparative analysis revealed, on the whole, that there were significantly different soil nutrient element contents, C/N, C/P, and N/P in Gossypium spp. fields compared to those of natural wetlands (P<0.05). The process of reclamation could significantly change the spatial distribution of nutrient elements in wetlands. Our results should be of importance in revealing the biogeochemical process of soil nutrient elements in coastal wetland and the influence of agricultural reclamation activities on the differentiation of soil nutrient elements.

[Predicting the potential distribution of dominant species of the coastal wetland in the Yellow River Delta, China using MaxEnt model]. / 基于MaxEnt模型的黄河三角洲滨海湿地优势植物群落潜在分布模拟.

Soil and vegetation community were investigated using the method of kilometer grid sampling. In addition, using the maximum entropy (MaxEnt) and the GIS spatial analysis technique, the potential distribution of dominant species in the Yellow River Delta and their major environmental variables and ecological parameters were quantitatively analyzed. The results showed that the dominant species of the coastal wetland were Tamarix chinensis, Phragmites australis and Suaeda salsa in the Yellow River Delta. Among the environmental variables, six variables were significant contributors to the potential distribution model of T. chinensis: NO3--N, salt, slope, Mg, altitude and NH4+-N. The environmental variables influencing the distribution of P. australis were NO3--N, salt, TP, pH, altitude and NH4+-N. NO3--N, salt and NH4+-N were the significant factors determining the potential distribution of S. salsa. The probability of presence of dominant species of the coastal wetland in the Yellow River Delta was positively correlated with salt, but it was negatively correlated with the other major environmental variables. The model predicted that the core potential distribution of dominant species in the Yellow River Delta was mainly in the coastal areas. In addition, P. australis had a wider range of distribution, compared with T. chinensis and S. salsa.

[Evolution process and related driving mechanisms of Yellow River Delta since the diversion of Yellow River].

Based on the 23 sheets of remote sensing images from 1976 to 2009, in combining with the water and sediment data from Lijin station and the annual precipitation data of Yellow River Basin from 1976 to 2008, this paper quantitatively analyzed the features of water and sediment discharge from Yellow River, and the evolution process of Yellow River Delta and related driving mechanisms. In 1976-2008, the annual runoff and the annual sediment discharge into sea changed largely and frequently, but overall, presented a decreasing trend. Since the course of the Yellow River changed its direction to Qingshui channel in 1976, the Delta coastline and area were generally in a silting-up state. The evolution process of the Delta could be approximately divided into three stages, i.e., 1976-1985, 1986-1995, and 1996-2009, and the increasing rate of the Delta decreased with the stages. The coastline and area of the Delta were significantly exponentially correlated to the sediment accumulated at Lijin station, and the inter-annual variation of the precipitation of the Yellow River Basin had a strong correlation with that of the sediment at Lijin station, suggesting that the annual variation of the precipitation in Yellow River Basin was the main factor affecting the runoff and sediment discharge into sea.