Vascular Endothelial Cells and Innate Immunity Shao, Ying; Saredy, Jason; Yang, William Y ...
Arteriosclerosis, thrombosis, and vascular biology,
2020-June, Volume:
40, Issue:
6
Journal Article
Peer reviewed
Open access
In addition to the roles of endothelial cells (ECs) in physiological processes, ECs actively participate in both innate and adaptive immune responses. We previously reported that, in comparison to ...macrophages, a prototypic innate immune cell type, ECs have many innate immune functions that macrophages carry out, including cytokine secretion, phagocytic function, antigen presentation, pathogen-associated molecular patterns-, and danger-associated molecular patterns-sensing, proinflammatory, immune-enhancing, anti-inflammatory, immunosuppression, migration, heterogeneity, and plasticity. In this highlight, we introduce recent advances published in both ATVB and many other journals(1) several significant characters classify ECs as novel immune cells not only in infections and allograft transplantation but also in metabolic diseases; (2) several new receptor systems including conditional danger-associated molecular pattern receptors, nonpattern receptors, and homeostasis associated molecular patterns receptors contribute to innate immune functions of ECs; (3) immunometabolism and innate immune memory determine the innate immune functions of ECs; (4) a great induction of the immune checkpoint receptors in ECs during inflammations suggests the immune tolerogenic functions of ECs; and (5) association of immune checkpoint inhibitors with cardiovascular adverse events and cardio-oncology indicates the potential contributions of ECs as innate immune cells.
As a gram-positive foodborne pathogen, Listeria monocytogenes (LM) can cause many serious diseases to the human health coupled with high mortality rates; thus, constructing an effective method to ...detect LM is of great significance. Herein, a novel sandwich-type electrochemical immunosensor is proposed for LM by introducing 3,4,9,10-perylene tetracarboxylic acid/graphene ribbons (PTCA/GNR) nanohybrids as a sensing platform and ferrocene/gold nanoparticles (Fc/Au NPs) as a signal amplifier. The high conductivity and large surface area of GNR can increase the immobilizing amount of the primary antibody (PAb) and enhance the electron transport rate, while Au NPs can carry secondary antibodies (SAb) and Fc derivative (Fc-SH) to form a SAb-Au NPs-Fc signal amplifier. Through using Fc molecules as a signal probe, its peak current can appear and increase varied from the LM concentrations; hence, a highly sensitive sandwich-type immunosensor was constructed wide linear range from 10 to 2 × 104-CFU mL−1 and low limit of detection of low to 6 CFU mL−1. Furthermore, the specificity of the immunosensor was also studied and a satisfactory result was obtained.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Norfloxacin (NFX) and sulfadiazine (SDZ) are two widely used antibiotics belonging to fluoroquinolone and sulfonamide groups, respectively, and have become the commonly detected micropollutants in ...aquatic environments. However, only few works have been conducted to investigate the highly probable inhibition of these antibiotic pollutants to Arthrospira platensis, which is an important species of cyanobacteria that is one of primary producers in aquatic ecosystems and should be remarkably sensitive to environmental pollutants due to its prokaryotic characteristics. Hence, the toxicological effects and removal efficiencies of NFX and SDZ in culturing A. platensis were studied by analyzing the biomass growth, photosynthetic pigments, primary biocomponents, and antibiotics concentration. The corresponding variations of these characteristics showed the higher sensitivity of A. platensis to NFX than to SDZ, indicating the specifically targeted effect of NFX on A. platensis, which could be confirmed in silico by the higher binding affinity of NFX with the critical enzyme. The obtained results illustrated the roles of NFX and SDZ on the growth of A. platensis, thus providing the great support in employing A. platensis to reduce hazards from contaminated water and recover biomass resources.
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•S. platensis showed higher sensitivity to norfloxacin than to sulfadiazine.•Photosynthetic pigments and primary biocomponents varied with antibiotics level.•Removal of norfloxacin was observed in the cultivation process.•Target effect of NFX on S. platensis is confirmed by the high binding affinity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 ...domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The number of early gastric cancer (EGC) cases has been increasing because of improved diagnostic procedures. Applications of function-preserving gastric cancer surgery may therefore also be ...increasing because of its low incidence of lymph node metastasis, excellent survival rates, and the possibility of less-invasive procedures such as laparoscopic gastrectomy being used in combination. Pylorus-preserving gastrectomy (PPG) with radical lymph node dissection is one such function-preserving procedure that has been applied for EGC, with the indications, limitations, and survival benefits of PPG already reported in several retrospective studies. Laparoscopy-assisted proximal gastrectomy has also been applied for EGC of the upper third of the stomach, although this procedure can be associated with the 2 major problems of reflux esophagitis and carcinoma arising in the gastric stump. In the patient with EGC in the upper third of the stomach, laparoscopy-assisted subtotal gastrectomy with a preserved very small stomach may provide a better quality of life for the patients and fewer postoperative complications. Finally, the laparoscopy endoscopy cooperative surgery procedure combines endoscopic submucosal dissection with laparoscopic gastric wall resection, which prevents excessive resection and deformation of the stomach after surgery and was recently applied for EGC cases without possibility of lymph node metastasis. Function-preserving laparoscopic gastrectomy is recommended for the treatment of EGC if the indication followed by accurate diagnosis is strictly confirmed. Preservation of remnant stomach sometimes causes severe postoperative dysfunctions such as delayed gastric retention in PPG, esophageal reflux in PG, and gastric stump carcinoma in the remnant stomach. Moreover, these techniques present technical difficulties to the surgeon. Although many retrospective studies showed the functional benefit or oncological safety of function-preserving gastrectomy, further prospective studies using large case series are necessary.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
RATIONALE:Endothelial injury is an initial mechanism mediating cardiovascular disease.
OBJECTIVE:Here, we investigated the effect of hyperhomocysteinemia on programed cell death in endothelial cells ...(EC).
METHODS AND RESULTS:We established a novel flow-cytometric gating method to define pyrotosis (Annexin V/Propidium iodide). In cultured human EC, we found that(1) homocysteine and lipopolysaccharide individually and synergistically induced inflammatory pyroptotic and noninflammatory apoptotic cell death; (2) homocysteine/lipopolysaccharide induced caspase-1 activation before caspase-8, caspase-9, and caspase-3 activations; (3) caspase-1/caspase-3 inhibitors rescued homocysteine/lipopolysaccharide-induced pyroptosis/apoptosis, but caspase-8/caspase-9 inhibitors had differential rescue effect; (4) homocysteine/lipopolysaccharide-induced nucleotide-binding oligomerization domain, and leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) protein caused NLRP3-containing inflammasome assembly, caspase-1 activation, and interleukin (IL)-1β cleavage/activation; (5) homocysteine/lipopolysaccharide elevated intracellular reactive oxygen species, (6) intracellular oxidative gradient determined cell death destiny as intermediate intracellular reactive oxygen species levels are associated with pyroptosis, whereas high reactive oxygen species corresponded to apoptosis; (7) homocysteine/lipopolysaccharide induced mitochondrial membrane potential collapse and cytochrome-c release, and increased B-cell lymphoma 2–associated X protein/B-cell lymphoma 2 ratio which were attenuated by antioxidants and caspase-1 inhibitor; and (8) antioxidants extracellular superoxide dismutase and catalase prevented homocysteine/lipopolysaccharide -induced caspase-1 activation, mitochondrial dysfunction, and pyroptosis/apoptosis. In cystathionine β-synthase–deficient (Cbs) mice, severe hyperhomocysteinemia-induced caspase-1 activation in isolated lung EC and caspase-1 expression in aortic endothelium, and elevated aortic caspase-1, caspase-9 protein/activity and B-cell lymphoma 2–associated X protein/B-cell lymphoma 2 ratio in Cbs aorta and human umbilical vein endothelial cells. Finally, homocysteine-induced DNA fragmentation was reversed in caspase-1 EC. Hyperhomocysteinemia-induced aortic endothelial dysfunction was rescued in caspase-1 and NLRP3 mice.
CONCLUSIONS:Hyperhomocysteinemia preferentially induces EC pyroptosis via caspase-1–dependent inflammasome activation leading to endothelial dysfunction. We termed caspase-1 responsive pyroptosis and apoptosis as pyrop-apoptosis.
Reactive oxygen species (ROS) are critical for the progression of cardiovascular diseases, inflammations and tumors. However, the mechanisms of how ROS sense metabolic stress, regulate metabolic ...pathways and initiate proliferation, inflammation and cell death responses remain poorly characterized. In this analytic review, we concluded that: 1) Based on different features and functions, eleven types of ROS can be classified into seven functional groups: metabolic stress-sensing, chemical connecting, organelle communication, stress branch-out, inflammasome-activating, dual functions and triple functions ROS. 2) Among the ROS generation systems, mitochondria consume the most amount of oxygen; and nine types of ROS are generated; thus, mitochondrial ROS systems serve as the central hub for connecting ROS with inflammasome activation, trained immunity and immunometabolic pathways. 3) Increased nuclear ROS production significantly promotes cell death in comparison to that in other organelles. Nuclear ROS systems serve as a convergent hub and decision-makers to connect unbearable and alarming metabolic stresses to inflammation and cell death. 4) Balanced ROS levels indicate physiological homeostasis of various metabolic processes in subcellular organelles and cytosol, while imbalanced ROS levels present alarms for pathological organelle stresses in metabolic processes. Based on these analyses, we propose a working model that ROS systems are a new integrated network for sensing homeostasis and alarming stress in metabolic processes in various subcellular organelles. Our model provides novel insights on the roles of the ROS systems in bridging metabolic stress to inflammation, cell death and tumorigenesis; and provide novel therapeutic targets for treating those diseases. (Word count: 246).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The DS-1 satellite was launched successfully on 3 June 2021 from the Taiyuan Satellite Launch Center. The satellite is equipped with a 1 m panchromatic and a 4 m multispectral sensor, providing ...high-resolution and wide-field optical remote sensing imaging capabilities. For satellites equipped with panchromatic and multispectral sensors, conventional geometric processing methods in the past involved separate calibration for the panchromatic sensor and the multispectral sensor. This method produced distinct internal and external calibration parameters in the respective bands, and also resulted in nonlinear geometric misalignments between the panchromatic and multispectral images due to satellite chattering and other factors. To better capitalize on the high spatial resolution of panchromatic imagery and the superior spectral resolution of multispectral imagery, it is necessary to perform registration on the calibrated panchromatic and multispectral images. When registering separately calibrated panchromatic and multispectral images, poor consistency between panchromatic and multispectral images leads to a small number of corresponding points, resulting in poor accuracy and registration effects. To address this issue, we propose a joint panchromatic and multispectral calibration method to register the panchromatic and multispectral images. Before geometric calibration, it is necessary to perform corresponding points matching. When matching, the small interval between the panchromatic and multispectral Charge-Coupled Devices (CCDs) results in a small intersection angle of the corresponding points between the panchromatic and multispectral images. As a result of this, the consistency between the spectral bands significantly improves, and the corresponding points match to have a more uniform distribution and a wider coverage. The technique enhances the consistent registration accuracy of both the panchromatic and multispectral bands. Experiments demonstrate that the joint calibration method yields a registration accuracy of panchromatic and multispectral bands exceeding 0.3 pixels.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Highlights • The expression level of Bmal1 is downregulated in pancreatic cancer (PC) tissues. • Bmal 1 significantly inhibits the proliferation and invasion of PC cells, both in vitro and in vivo. • ...Bmal1 could directly bind to the p53 gene promoter. • Bmal1 is able to induce apoptosis and G2/M cell cycle arrest in PC cells in a p53-dependent manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
We determined the
f
odd,Ba
values, 0.46 ± 0.08, 0.51 ± 0.09, 0.50 ± 0.13, and 0.48 ± 0.12, that correspond to the r-contribution 100% for four r-II stars, CS 29491-069, HE 1219-0312, HE ...2327-5642, and HE 2252-4225, respectively. Our results suggest that almost all of the heavy elements (in the range from Ba to Pb) in r-II stars have a common origin, that is, from a single r-process (the main r-process). We found that the
f
odd,Ba
has an intrinsic nature, and should keep a constant value of about 0.46 in the main r-process yields, which is responsible for the heavy element enhancement of r-II stars and of our Galaxy chemical enhancement. In addition, except for the abundance ratio Ba/Eu the
f
odd,Ba
is also an important indicator, which can be used to study the relative contributions of the r- and s-processes during the chemical evolution history of the Milky Way and the enhancement mechanism in stars with peculiar abundances of heavy elements.
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