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"Xia, Yuan"
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Lipopolysaccharide (LPS) Aggravates High Glucose- and Hypoxia/Reoxygenation-Induced Injury through Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis in H9C2 Cardiomyocytes
Diabetes aggravates myocardial ischemia-reperfusion (I/R) injury because of the combination effects of changes in glucose and lipid energy metabolism, oxidative stress, and systemic inflammatory response. Studies have indicated that myocardial I/R may coincide and interact with sepsis and inflammation. However, the role of LPS in hypoxia/reoxygenation (H/R) injury in cardiomyocytes under high glucose conditions is still unclear. Our objective was to examine whether lipopolysaccharide (LPS) could aggravate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by upregulating ROS production to activate NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes. H9C2 cardiomyocytes were exposed to HG (30 mM) condition with or without LPS, along with caspase-1 inhibitor (Ac-YVAD-CMK), inflammasome inhibitor (BAY11-7082), ROS scavenger N-acetylcysteine (NAC), or not for 24 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). The cell viability, lactate dehydrogenase (LDH) release, caspase-1 activity, and intracellular ROS production were detected by using assay kits. The incidence of pyroptosis was detected by calcein-AM/propidium iodide (PI) double staining kit. The concentrations of IL-1β and IL-18 in the supernatants were assessed by ELISA. The mRNA levels of NLRP3, ASC, and caspase-1 were detected by qRT-PCR. The protein levels of NF-κB p65, NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18 were detected by western blot. The results indicated that pretreatment LPS with 1 μg/ml not 0.1 μg/ml could efficiently aggravate HG and H/R injury by activating NLRP3 inflammasome to mediate pyroptosis in H9C2 cells, as evidenced by increased LDH release and decreased cell viability in the cells, and increased expression of NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18. Meanwhile, Ac-YVAD-CMK, BAY11-7082, or NAC attenuated HG- and H/R-induced H9C2 cell injury with LPS stimulated by reversing the activation of NLRP3 inflammasome-mediated pyroptosis. In conclusion, LPS could increase the sensitivity of H9C2 cells to HG and H/R and aggravated HG- and H/R-induced H9C2 cell injury by promoting ROS production to induce NLRP3 inflammasome-mediated pyroptosis.
Journal Article
Cellular Toxicity and Immunological Effects of Carbon-based Nanomaterials
Background
Carbon nanomaterials are a growing family of materials featuring unique physicochemical properties, and their widespread application is accompanied by increasing human exposure.
Main body
Considerable efforts have been made to characterize the potential toxicity of carbon nanomaterials in vitro and in vivo. Many studies have reported various toxicology profiles of carbon nanomaterials. The different results of the cytotoxicity of the carbon-based materials might be related to the differences in the physicochemical properties or structures of carbon nanomaterials, types of target cells and methods of particle dispersion,
etc.
The reported cytotoxicity effects mainly included reactive oxygen species generation, DNA damage, lysosomal damage, mitochondrial dysfunction and eventual cell death via apoptosis or necrosis. Despite the cellular toxicity, the immunological effects of the carbon-based nanomaterials, such as the pulmonary macrophage activation and inflammation induced by carbon nanomaterials, have been thoroughly studied. The roles of carbon nanomaterials in activating different immune cells or inducing immunosuppression have also been addressed.
Conclusion: Here, we provide a review of the latest research findings on the toxicological profiles of carbon-based nanomaterials, highlighting both the cellular toxicities and immunological effects of carbon nanomaterials. This review provides information on the overall status, trends, and research needs for toxicological studies of carbon nanomaterials.
Journal Article
Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients
PurposeTo assess the management and safety of epidural or general anesthesia for Cesarean delivery in parturients with coronavirus disease (COVID-19) and their newborns, and to evaluate the standardized procedures for protecting medical staff.MethodsWe retrospectively reviewed the cases of parturients diagnosed with severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection disease (COVID-19). Their epidemiologic history, chest computed tomography scans, laboratory measurements, and SARS-CoV-2 nucleic acid positivity were evaluated. We also recorded the patients’ demographic and clinical characteristics, anesthesia and surgery-related data, maternal and neonatal complications, as well as the health status of the involved medical staff.ResultsThe clinical characteristics of 17 pregnant women infected with SARS-CoV-2 were similar to those previously reported in non-pregnant adult patients. All of the 17 patients underwent Cesarean delivery with anesthesia performed according to standardized anesthesia/surgery procedures. Fourteen of the patients underwent continuous epidural anesthesia with 12 experiencing significant intraoperative hypotension. Three patients received general anesthesia with tracheal intubation because emergency surgery was needed. Three of the parturients are still recovering from their Cesarean delivery and are receiving in-hospital treatment for COVID-19. Three neonates were born prematurely. There were no deaths or serious neonatal asphyxia events. All neonatal SARS-CoV-2 nucleic acid tests were negative. No medical staff were infected throughout the patient care period.ConclusionsBoth epidural and general anesthesia were safely used for Cesarean delivery in the parturients with COVID-19. Nevertheless, the incidence of hypotension during epidural anesthesia appeared excessive. Proper patient transfer, medical staff access procedures, and effective biosafety precautions are important to protect medical staff from COVID-19.
Journal Article
Validity of chronic restraint stress for modeling anhedonic-like behavior in rodents: a systematic review and meta-analysis
Background
Chronic restraint stress (CRS) is widely used to recapitulate depression phenotypes in rodents but is frequently criticized for a perceived lack of efficacy. The aim of this study was to evaluate anhedonic-like behavior in the CRS model in rodents by performing a meta-analysis of studies that included sucrose preference tests.
Methods
This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. We comprehensively searched for eligible studies published before June 2021 in the PubMed, Embase, Medline, and Web of Science databases. We chose sucrose preference ratio as the indicative measure of anhedonia because it is a core symptom of depression in humans.
Results
Our pooled analysis included 34 articles with 57 studies and seven rodent species/strains and demonstrated decreased sucrose preference in the stress group compared with controls. The duration of CRS differentially affected the validity of anhedonic-like behavior in the models. Rats exhibited greater susceptibility to restraint stress than mice, demonstrating inter-species variability.
Conclusions
Our meta-analysis of studies that used the CRS paradigm to evaluate anhedonic-like behavior in rodents was focused on a core symptom of depression (anhedonia) as the main endpoint of the model and identified species-dependent susceptibility to restraint stress.
Journal Article
Seed germination response to high temperature and water stress in three invasive Asteraceae weeds from Xishuangbanna, SW China
Crassocephalum crepidioides, Conyza canadensis, and Ageratum conyzoides are alien annuals naturalized in China, which produce a large number of viable seeds every year. They widely grow in Xishuangbanna, becoming troublesome weeds that compete with crops for water and nutrients. As seed germination is among the most important life-stages which contribute to plant distribution and invasiveness, its adaptation to temperature and water stress were investigated in these three species. Results showed that: (1) These three species have wide temperature ranges to allow seed germination, i.e., high germination and seedling percentages were achieved between 15°C and 30°C, but germination was seriously inhibited at 35°C; only A. conyzoides demonstrated relative preference for warmer temperatures with approximately 25% germination and seedling percentage at 35°C; (2) light was a vital germination prerequisite for C. crepidioides and A. conyzoides, whereas most C. canadensis seeds germinated in full darkness; (3) Although all three species have good adaptation to bare ground habitat characterized by high temperatures and water stress, including their tolerance to soil surface temperatures of 70°C in air-dried seeds, A. conyzoides seeds exhibited higher tolerance to both continuous and daily periodic high-temperature treatment at 40°C, and to water restriction (e.g., ca. 65% seeds germinated to -0.8 MPa created by NaCl), which is consistent with their field behavior in Xishuangbanna. This study suggests that seed high-temperature tolerance contributes to the weed attributes of these three species, and that adaptation to local micro-habitats is a critical determinant for invasiveness of an alien plant.
Journal Article
Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain–barrier disruption after ischemic stroke
Endothelium (EC) is a key component of blood–brain barrier (BBB), and has an important position in the neurovascular unit. Its dysfunction and death after cerebral ischemic/reperfusion (I/R) injury not only promote evolution of neuroinflammation and brain edema, but also increase the risk of intracerebral hemorrhage of thrombolytic therapies. However, the mechanism and specific interventions of EC death after I/R injury are poorly understood. Here we showed that necroptosis was a mechanism underlying EC death, which promoted BBB breakdown after I/R injury. Treatment of rats with receptor interacting protein kinase 1 (RIPK1)-inhibitor, necrostatin-1 reduced endothelial necroptosis and BBB leakage. We furthermore showed that perivascular M1-like microglia-induced endothelial necroptosis leading to BBB disruption requires tumor necrosis factor-α (TNF-α) secreted by M1 type microglia and its receptor, TNF receptor 1 (TNFR1), on endothelium as the primary mediators of these effects. More importantly, anti-TNFα (infliximab, a potent clinically used drug) treatment significantly ameliorate endothelial necroptosis, BBB destruction and improve stroke outcomes. Our data identify a previously unexplored role for endothelial necroptosis in BBB disruption and suggest infliximab might serve as a potential drug for stroke therapy.
Journal Article
Protective Effect of Ginsenoside Rb1 against Intestinal Ischemia-Reperfusion Induced Acute Renal Injury in Mice
Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway.
Journal Article
Tandem utilization of CO2 photoreduction products for the carbonylation of aryl iodides
Photocatalytic CO
2
reduction reaction has been developed as an effective strategy to convert CO
2
into reusable chemicals. However, the reduction products of this reaction are often of low utilization value. Herein, we effectively connect photocatalytic CO
2
reduction and amino carbonylation reactions in series to reconvert inexpensive photoreduction product CO into value-added and easily isolated fine chemicals. In this tandem transformation system, we synthesize an efficient photocatalyst, NNU-55-Ni, which is transformed into nanosheets (NNU-55-Ni-NS) in situ to improve the photocatalytic CO
2
-to-CO activity significantly. After that, CO serving as reactant is further reconverted into organic molecules through the coupled carbonylation reactions. Especially in the carbonylation reaction of diethyltoluamide synthesis, CO conversion reaches up to 85%. Meanwhile, this tandem transformation also provides a simple and low-cost method for the
13
C isotopically labeled organic molecules. This work represents an important and feasible pathway for the subsequent separation and application of CO
2
photoreduction product.
A Ni-based MOF catalyst is reported to facilitate the photocatalytic reduction of CO2 to CO, a low-value product. In tandem, the as-produced CO is used as a reactant in the Pd-catalyzed carbonylation of aryl halides and other fine organic chemicals.
Journal Article