Carbon nanodots in endothelial cells and C57BL/6 mice: a study of toxicity and anti-inflammatory effect

The advancement of therapy for cardiovascular disease (CVD) is paramount to public health, as it is the leading global cause of mortality [1]. Nanomedicine provides new opportunities in the ongoing efforts to reduce the economic and healthcare consequences of CVD. Carbon nanodots (CNDs) green-synthesized from microwave pyrolysis of ethylenediamine and citric acid are spherical, ~3 nm in diameter, and possess exceptional hydrophilic, biocompatible, fluorescent, and anti-oxidant properties. However, there is no current report on how these CNDs affect the cardiovascular system, particularly their potential in mediating endothelial dysfunction and cardiovascular disease (CVD). As a known biomarker of inflammation, Oxidized-LDL (Ox-LDL) induces inflammatory gene expression and monocyte extravasation that leads to atherosclerotic development. This study examines the role of CNDs in mediating Ox-LDL induced inflammation in human microvascular endothelial cells (HMEC-1). Our results demonstrate that CNDs can reduce Ox-LDL induced monocyte adhesion in HMEC-1s, which demonstrates their anti-inflammatory effects. The relative gene expression of the cytokine interleukin-8 (IL-8) was reduced by the addition of CNDs, which implies their action in mediating monocyte recruitment to the site of inflammation. While reactive oxygen species (ROS) perform many essential functions, their overproduction disrupts cellular oxidative balance, induces EC dysfunction, and leads to an inflammatory state. Studying the action of CNDs through Electron paramagnetic resonance (EPR) spectroscopy showed direct superoxide and hydroxyl radical-scavenging by CNDs. This result implies that the anti-inflammatory effects of CNDs seen in vitro are attributed to their direct scavenging of ROS. Furthermore, CNDs were found to ameliorate the cytotoxicity caused by Ox-LDL in HMEC-1s. Viability assays showed CNDs were not cytotoxic at measured concentrations to HMEC-1s in vitro. Animal studies involving mice did not show any morphological or physical changes between the CND and control groups. These collective results demonstrate the potential of CNDs to reduce inflammation and cytotoxicity caused by Ox-LDL in HMEC-1s, which implies their use in the development of novel therapy for cardiovascular disease

Carbon Nanodots Inhibit Tumor Necrosis Factor-α-Induced Endothelial Inflammation through Scavenging Hydrogen Peroxide and Upregulating Antioxidant Gene Expression in EA.hy926 Endothelial Cells

Carbon nanodots (CNDs) are a new type of nanomaterial with a size of less than 10 nanometers and excellent biocompatibility, widely used in fields such as biological imaging, transmission, diagnosis, and drug delivery. However, its potential and mechanism to mediate endothelial inflammation have yet to be explored. Here, we report that the uptake of CNDs by EA.hy926 endothelial cells is both time and dose dependent. The concentration of CNDs used in this experiment was found to not affect cell viability. TNF-α is a known biomarker of vascular inflammation. Cells treated with CNDs for 24 h significantly inhibited TNF-α (0.5 ng/mL)-induced expression of intracellular adhesion molecule 1 (ICAM-1) and interleukin 8 (IL-8). ICAM-1 and IL-8 are two key molecules responsible for the activation and the firm adhesion of monocytes to activated endothelial cells for the initiation of atherosclerosis. ROS, such as hydrogen peroxide, play an important role in TNF-α-induced inflammation. Interestingly, we found that CNDs effectively scavenged H2O2 in a dose-dependent manner. CNDs treatment also increased the activity of the antioxidant enzyme NQO1 in EA.hy926 endothelial cells indicating the antioxidant properties of CNDs. These results suggest that the anti-inflammatory effects of CNDs may be due to the direct H2O2 scavenging properties of CNDs and the indirect upregulation of antioxidant enzyme NQO1 activity in endothelial cells. In conclusion, CND can inhibit TNF-α-induced endothelial inflammation, possibly due to its direct scavenging of H2O2 and the indirect upregulation of antioxidant enzyme NQO1 activity in endothelial cells

Recent Advances in Carbon Nanodots: A Promising Nanomaterial for Biomedical Applications

Carbon nanodots (CNDs) are an emerging class of nanomaterials and have generated much interest in the field of biomedicine by way of unique properties, such as superior biocompatibility, stability, excellent photoluminescence, simple green synthesis, and easy surface modification. CNDs have been featured in a host of applications, including bioimaging, biosensing, and therapy. In this review, we summarize the latest research progress of CNDs and discuss key advances in our comprehension of CNDs and their potential as biomedical tools. We highlighted the recent developments in the understanding of the functional tailoring of CNDs by modifying dopants and surface molecules, which have yielded a deeper understanding of their antioxidant behavior and mechanisms of action. The increasing amount of in vitro research regarding CNDs has also spawned interest in in vivo practices. Chief among them, we discuss the emergence of research analyzing CNDs as useful therapeutic agents in various disease states. Each subject is debated with reflection on future studies that may further our grasp of CNDs

Carbon Nanodots Inhibit Tumor Necrosis Factor-α-Induced Endothelial Inflammation through Scavenging Hydrogen Peroxide and Upregulating Antioxidant Gene Expression in EA.hy926 Endothelial Cells

Carbon nanodots (CNDs) are a new type of nanomaterial with a size of less than 10 nanometers and excellent biocompatibility, widely used in fields such as biological imaging, transmission, diagnosis, and drug delivery. However, its potential and mechanism to mediate endothelial inflammation have yet to be explored. Here, we report that the uptake of CNDs by EA.hy926 endothelial cells is both time and dose dependent. The concentration of CNDs used in this experiment was found to not affect cell viability. TNF-α is a known biomarker of vascular inflammation. Cells treated with CNDs for 24 h significantly inhibited TNF-α (0.5 ng/mL)-induced expression of intracellular adhesion molecule 1 (ICAM-1) and interleukin 8 (IL-8). ICAM-1 and IL-8 are two key molecules responsible for the activation and the firm adhesion of monocytes to activated endothelial cells for the initiation of atherosclerosis. ROS, such as hydrogen peroxide, play an important role in TNF-α-induced inflammation. Interestingly, we found that CNDs effectively scavenged H2O2 in a dose-dependent manner. CNDs treatment also increased the activity of the antioxidant enzyme NQO1 in EA.hy926 endothelial cells indicating the antioxidant properties of CNDs. These results suggest that the anti-inflammatory effects of CNDs may be due to the direct H2O2 scavenging properties of CNDs and the indirect upregulation of antioxidant enzyme NQO1 activity in endothelial cells. In conclusion, CND can inhibit TNF-α-induced endothelial inflammation, possibly due to its direct scavenging of H2O2 and the indirect upregulation of antioxidant enzyme NQO1 activity in endothelial cells

From Fear to Preparedness: A Systematic Review of Parents' Awareness and Use of Epinephrine Autoinjectors

This systematic review aims to synthesize existing literature on parents' knowledge and use of epinephrine autoinjectors (EAIs) and identify factors associated with correct use and barriers to education and training. A comprehensive search was conducted on PubMed and the Directory of Open Access Journals (DOAJ) using keywords and MeSH terms. Inclusion and exclusion criteria were established, and papers were screened for eligibility. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal tool. A total of 1008 papers were initially identified, with 214 remaining after applying filters. Following screening and quality assessment, seven observational studies were included in the review. The studies found that while most caregivers claimed to carry an EAI on their person and practiced its use at home after training, it was often not used during allergic reactions. The most common reason cited for not using EAI was uncertainty about whether the symptoms were severe enough to warrant EAI use. The lack of EAI use was significantly associated with lower caregiver confidence in using EAI. Those who received EAI during oral food challenges (OFC) and in the community had increased confidence in administering the EAI from pre-OFC to follow-up compared to those who did not receive EAI at all. Targeted interventions and educational strategies should be developed to improve parent knowledge and use of EAIs

Effect of Sacubitril-Valsartan on Quality of Life, Functional and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (HFpEF): A Systematic Review of Randomized Clinical Trials

Background: Sacubitril/Valsartan use in heart failure has shown promising results in early trials. However, the effects on the overall functional capacity, exercise capacity, and quality of life are unknown. Aims: We aimed to understand the results of studies that attempted to measure these outcomes that affect the mobility and day-to-day life of these patients. Methods: MEDLINE, PubMed, PubMed Central (PMC), Google Scholar, ClinicalTrials.gov, and ISRCTN were explored to look for clinical trials relevant to the literature. Results: A total of three high-quality randomized controlled trials were discovered that evaluated the effect of sacubitril-valsartan on functional capacity, exercise capacity, or quality of life. All of them were industry-funded and revealed no statistical difference in the mentioned outcomes. No study measured peak oxygen uptake or ventilation/carbon dioxide ratio slope. Conclusion: Sacubitril-valsartan had minimal to no impact on functional capacity, exercise capacity, or quality of life. However, future prospective studies with more sensitive outcome measures should be conducted to validate the findings

Effect of Sacubitril-Valsartan on Quality of Life, Functional and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (HFpEF): A Systematic Review of Randomized Clinical Trials

Background: Sacubitril/Valsartan use in heart failure has shown promising results in early trials. However, the effects on the overall functional capacity, exercise capacity, and quality of life are unknown. Aims: We aimed to understand the results of studies that attempted to measure these outcomes that affect the mobility and day-to-day life of these patients. Methods: MEDLINE, PubMed, PubMed Central (PMC), Google Scholar, ClinicalTrials.gov, and ISRCTN were explored to look for clinical trials relevant to the literature. Results: A total of three high-quality randomized controlled trials were discovered that evaluated the effect of sacubitril-valsartan on functional capacity, exercise capacity, or quality of life. All of them were industry-funded and revealed no statistical difference in the mentioned outcomes. No study measured peak oxygen uptake or ventilation/carbon dioxide ratio slope. Conclusion: Sacubitril-valsartan had minimal to no impact on functional capacity, exercise capacity, or quality of life. However, future prospective studies with more sensitive outcome measures should be conducted to validate the findings

Immunotherapy for Post-COVID Neuropsychiatric Symptoms: The Potential of IVIG Treatment

This paper explores the neuropsychiatric consequences of SARS-CoV-2 (COVID-19) infection, specifically the use of intravenous immunoglobulin (IVIG) therapy in treating central nervous system (CNS) symptoms associated with COVID-19. The authors searched PubMed and Google Scholar using the keywords "IVIG" and "covid-19 neuropsychiatric symptoms" to find five articles, including three case reports, a retrospective study, and a prospective study, that detail the experiences of individuals with persistent neuropsychiatric symptoms after contracting COVID-19. The neuropsychiatric symptoms reported in the analyzed studies include sleep disturbance, exhaustion, cognitive decline, anxiety, and others. Common treatments for post-COVID neuropsychiatric symptoms include medications, cognitive behavioral therapy, and lifestyle modifications. IVIG therapy to manage CNS symptoms of COVID-19 has shown mixed results in studies, with some showing positive effects while others remain inconclusive. Further research is needed to understand this therapy's potential benefits and limitations fully