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.
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.
Purpose
To 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.
Methods
We 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.
Results
The 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.
Conclusions
Both 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.
Carbon nanomaterials are a growing family of materials featuring unique physicochemical properties, and their widespread application is accompanied by increasing human exposure.
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.
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.
The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were ...unintentionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes.
We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020.
Of the 34 operative patients, the median age was 55 years (IQR, 43–63), and 20 (58·8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 91·2%), fatigue (25 73·5%) and dry cough (18 52·9%). 15 (44·1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20·5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury.
In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44·1%) patients needed ICU care, and the mortality rate was 20·5%.
National Natural Science Foundation of China.
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.
Molecular recognition, which is the process of biological macromolecules interacting with each other or various small molecules with a high specificity and affinity to form a specific complex, ...constitutes the basis of all processes in living organisms. Proteins, an important class of biological macromolecules, realize their functions through binding to themselves or other molecules. A detailed understanding of the protein-ligand interactions is therefore central to understanding biology at the molecular level. Moreover, knowledge of the mechanisms responsible for the protein-ligand recognition and binding will also facilitate the discovery, design, and development of drugs. In the present review, first, the physicochemical mechanisms underlying protein-ligand binding, including the binding kinetics, thermodynamic concepts and relationships, and binding driving forces, are introduced and rationalized. Next, three currently existing protein-ligand binding models--the "lock-and-key", "induced fit", and "conformational selection"--are described and their underlying thermodynamic mechanisms are discussed. Finally, the methods available for investigating protein-ligand binding affinity, including experimental and theoretical/computational approaches, are introduced, and their advantages, disadvantages, and challenges are discussed.
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.
Background
Tumor biomarkers have used widely in clinical oncology in human medicine. Only a few studies have evaluated the clinical utility of tumor biomarkers for veterinary medicine. A test for ...fibrinogen and fibrin degradation products (DR‐70) has been proposed as an ideal biomarker for tumors in humans. The clinical value of DR‐70 for veterinary medicine however has yet to be determined.
Objectives
Investigate the diagnostic value of DR‐70 concentrations by comparing them between healthy dogs and dogs with tumors.
Animals
Two hundred sixty‐three dogs with different types of tumors were included. Sixty healthy dogs also were recruited for comparison.
Methods
The DR‐70 concentrations were measured in all recruited individuals by ELISA. Clinical conditions were categorized based on histopathology, cytology, ultrasound examination, radiology, clinical findings, and a combination of these tests.
Results
The median concentration of DR‐70 was 2.130 ± 0.868 μg/mL in dogs with tumors, which was significantly higher than in healthy dogs (1.202 ± 0.610 μg/mL; P < .0001). With a cut‐off of 1.514 μg/mL, the sensitivity and specificity of DR‐70 were 84.03% and 78.33%, respectively. The area under curve was 0.883. The DR‐70 concentration can be an effective tumor biomarker in veterinary medicine.
Conclusions and Clinical Importance
Increased DR‐70 concentrations were not affected by tumor type, sex, age, or body weight. However, in dogs with metastatic mast cell tumors and oral malignant melanoma, DR‐70 concentrations were significantly increased. Additional studies, including more dogs with nonneoplastic diseases, are needed to further evaluate the usefulness of DR‐70 as a tumor biomarker.
As a spreading addictive behaviour in recent years, internet gaming disorder (IGD) has been studied a lot and the overall research results indicate that IGD has a high prevalence among adolescents ...and young adults (AYAs). To update the status quo of prevalence, it is necessary to conduct comprehensive analyses.
On the premise of following the PRISMA statement, the study conducted two systematic reviews and meta-analyses to assess the global prevalence of IGD among AYAs and identify its possible risk factors. To achieve the goals, PubMed and CNKI databases were used to select the concerned studies published up to May 31, 2021. Heterogeneity was assessed using a funnel plot, Begg's test, Egger's test, and trim-and-fil method, followed by sensitivity analysis, subgroup analysis, and meta-regression analysis.
For the meta-analysis of prevalence, 407,620 participants from 155 reports in 33 countries were included. The pooled prevalence of IGD among AYAs was 9.9% (95% CI: 8.6%–11.3%, P = 0.000, I2 = 94.4%), including 8.8% (95% CI: 7.5%–10.0%) among adolescents and 10.4% (95% CI: 8.8%–11.9%) among young adults. The following 12 factors are the possible risk factors of IGD among AYAs, which are stress, long average game time, family dysfunction, poor academic performance, being bullied, bullying, interpersonal problems, hyperactivity/inattention, anxiety, depression, emotional distress and low self-esteem.
This study confirms the prevalence and possible risk factors for IGD among AYAs. It's valuable in understanding the threat of IGD and finding intervention strategies for IGD among AYAs.
•Provides updated global prevalence of internet gaming disorder among adolescents and young adults in summary (9.9%) and separately (8.8% vs 10.4%).•Higher prevalence of internet gaming disorder among adolescents and young adults in males (15.4%) compared to females (6.4%).•Identify 12 possible risk factors for internet gaming disorder among adolescents and young adults.
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