Pyroptosis is a caspase-1 or caspase-4/5/11-dependent programmed cell death associated with inflammation, which is initiated by inflammasomes or cytosolic LPS in innate immunity. Sepsis is a life-threatening organ dysfunction caused by an imbalance in the body's response to infection. It is a complex interaction between the pathogen and the host's immune system. Neutrophils play the role of a double-edged sword in sepsis, and a number of studies have previously shown that regulation of neutrophils is the most crucial part of sepsis treatment. Pyroptosis is one of the important forms for neutrophils to function, which is increasingly understood as a host active immune response. There is ample evidence that neutrophil pyroptosis may play an important role in sepsis. In recent years, a breakthrough in pyroptosis research has revealed the main mechanism of pyroptosis. However, the potential value of neutrophil pyroptosis in the treatment of sepsis did not draw enough attention. A literature review was performed on the main mechanism of pyroptosis in sepsis and the potential value of neutrophils pyroptosis in sepsis, which may be suitable targets for sepsis treatment in future.
Although the neutrophil recruitment cascade during inflammation has been well described, the molecular players that halt neutrophil chemotaxis remain unclear. In this study, we found that lipopolysaccharide (LPS) was a potent stop signal for chemotactic neutrophil migration. Treatment with an antagonist of the ATP receptor (P2X1) in primary human neutrophils or knockout of the P2X1 receptor in neutrophil-like differentiated HL-60 (dHL-60) cells recovered neutrophil chemotaxis. Further observations showed that LPS-induced ATP release through connexin 43 (Cx43) hemichannels was responsible for the activation of the P2X1 receptor and the subsequent calcium influx. Increased intracellular calcium stopped neutrophil chemotaxis by activating myosin light chain (MLC) through the myosin light chain kinase (MLCK)-dependent pathway. Taken together, these data identify a previously unknown function of LPS-induced autocrine ATP signaling in inhibiting neutrophil chemotaxis by enhancing MLC phosphorylation, which provides important evidence that stoppage of neutrophil chemotaxis at infectious foci plays a key role in the defense against invading pathogens.endotoxin | neutrophil | chemotaxis | ATP | myosin light chain N eutrophils are the most abundant leukocytes in humans and the first blood cells to arrive at infectious sites as part of the innate cellular immune response. Following transmigration out of the blood vessel, neutrophils migrate through interstitial tissue toward the foci of damage. Then, neutrophil recruitment mobilizes near the pathogenic sites to eliminate pathogens and necrotic tissue. Although the neutrophil recruitment cascade during inflammation has been well described, the molecules that stop neutrophil chemotaxis remain unclear.Studies in recent decades have confirmed that extracellular ATP, as a purinergic signaling molecule, participates in the pathogenesis of various inflammatory diseases such as transplantation rejection, autoimmune disease, and bacterial infection (1). As a result of ectoapyrases and ectoadenosine triphosphatases (ecto-ATPases), which hydrolyze ATP into adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO), the concentration of extracellular ATP is maintained at ∼10 nmol/L (2). However, the intracellular ATP concentration in mammalian cells is 5-8 mmol/L. Owing to the 10 6 -fold ATP gradient difference, cell necrosis or activation at inflammatory sites causes a dramatic ATP release (2). By activating the P2X (P2X1-7 subtypes) and P2Y (P2Y1, -2, -4, -6, and -11-14 subtypes) receptor families, extracellular ATP contributes to the regulation of a variety of inflammatory cell responses (3). Given the high concentration of ATP in inflammatory tissues, the effects of extracellular ATP/P2 receptors on neutrophil migration have attracted much attention. ATP released from the leading edge of the neutrophil surface amplifies chemotactic signals and directs cell orientation by feedback through the P2Y2 receptor (4). Knockout of the P2Y2 receptor decreases liver infi...
Flavanols, or flavan-3-ols, are a family of bioactive compounds present in cocoa, red wine, green tea, red grapes, berries and apples. With a basic monomer unit of (À)-epicatechin or (+)-catechin, flavanols can be present in foods and beverages as monomers or oligomers (procyanidins). Most, but not all, procyanidins are degraded into monomer or dimer units prior to absorption. The bioavailability of flavanols can be influenced by multiple factors, including food processing, cooking, digestion, and biotransformation. Flavanols are potent antioxidants, scavenging free radicals in vitro and in vivo. While some of the actions of flavanols can be linked to antioxidant activities, other modes of action may also occur, including modulation of intracellular signaling, effects on membrane fluidity and regulation of cytokine release or action. Physiologically, flavanolrich foods and beverages can affect platelet aggregation, vascular inflammation, endothelial nitric oxide metabolism, and may confer protective effects against neurodegeneration. Epidemiological data suggests that intake of cocoa, a rich source of flavanols, is inversely associated with 15-year cardiovascular and all-cause mortality in older males. (À)-Epicatechin and its metabolite, epicatechin-7-Oglucuronide, have been identified as independent predictors of some of the vascular effects associated with the consumption of a flavanol-rich beverage. Targeted dietary components and nutrition supplements that can influence the vascular system will be of great value in the prevention and treatment of chronic disease.
Objective:To estimate birth population-based perinatal-neonatal mortality and preterm rate in China from a regional survey in 2010.Study design:Data of total births in 2010 obtained from 151 level I–III hospitals in Huai’an, Jiangsu, were prospectively collected and analyzed.Results:From 61 227 birth registries (including 60 986 live births and 241 stillbirths), we derive a birth rate of 11.3‰ (of 5.4 million regional population), a male-to-female ratio of 116:100 and valid data from 60 615 newborns. Mean birth weight (BW) was 3441 ± 491 g with 13.6% macrosomia. Low BW was 2.8% (1691/60 372) with 8.83% mortality. Preterm rate was 3.72% (2239/60 264) with 7.61% mortality. Cesarean section rate was 52.9% (31 964/60 445), multiple pregnancy 1.8% (1088/60 567) and birth defects 6.7‰ (411/61 227). There were 97.4% healthy newborns and 2.2% (1298) requiring hospitalized after birth. The perinatal mortality was 7.7‰ (471/61 227, including 241 stillbirths, 230 early neonatal deaths). The neonatal mortality was 4.4‰ (269/60 986). The main causes of neonatal death were birth asphyxia (24.5%), respiratory diseases (21.5%), prematurity related organ dysfunction (18.5%) and congenital anomalies (7.7%), whereas incidence of congenital heart disease and respiratory distress syndrome was 8.6‰ and 6.1‰, respectively.Conclusions:This regional birth population-based data file contains low perinatal-neonatal mortality rates, associated with low proportion of LBW and preterm births, and incidences of major neonatal disease, by which we estimate, in a nationwide perspective, in 16 million annual births, preterm births should be around 800 000, perinatal and neonatal mortality may be 128 000–144 000 and 80 000–96 000, respectively, along with 100 000 respiratory distress syndrome.
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