Endothelial Cell Necrosis Research Articles

Dendrobium huoshanense stem polysaccharide exhibits gastroprotective effect via regulating PI3K/AKT, NF-κB and Nrf-2 signaling in high-salt diet-induced gastritis mice

Prolonged consumption of high-salt diet (HSD) is implicated in the development of gastritis. This research intends to explore the protective potential of Dendrobium huoshanense stem polysaccharide (cDHPS) on gastritis in high-salt diet mice. cDHPS effectively alleviated the symptoms of HSD-induced gastritis, which were demonstrated by the reversed weight loss, gastric mucosal swelling, gastric mucus depletion, tight junction (TJ) disruption, and microvascular endothelial cell necrosis. Notably, cDHPS inhibited HSD-induced gastric inflammation, which was evidenced by the remodeled balance of Th17/Treg cells, along with the decreased level of IL-17 and the increased level of IL-10. Simultaneously, the oxidative stress induced by HSD was also improved with cDHPS treatment. Western blot analysis revealed that cDHPS markedly upregulated Nrf-2 expression while concurrently inhibiting the phosphorylation of P65, IκB, PI3K, AKT and FOXO-1 in the gastric tissues of HSD-induced gastritis mice. Collectively, these results indicate that cDHPS possesses protective potential against HSD-induced gastritis, which was attributable to the improvement of inflammatory and oxidative damage by modulating the PI3K/AKT and NF-κB/Nrf-2 signaling.

The β2-adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury.

Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β2-adrenergic receptor (β2-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome. The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy. Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours. The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β2-AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels. Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.

Spock2 Functions as a Key Time-Series Gene of Endothelial Cells in Sepsis-Induced Cardiomyopathy.

The study aimed to investigate the pathogenesis of sepsis-induced cardiomyopathy, a leading cause of mortality in septic patients. Transcriptome data from cecal ligation and puncture-induced septic mice were analyzed at different time points (24, 48, and 72 hours) using GSE171546 data. Through weighted gene co-expression network analysis, time series, and differential expression analyses, key time-series differentially expressed genes were identified. In addition, single-cell sequencing data (GSE207363) were used for both differential and pseudotime analyses to pinpoint differentially expressed genes specific to endothelial cells. The study highlighted Spock2, S100a9, S100a8, and Xdh as differential genes specific to endothelial cells in a time-dependent manner. Immunofluorescence validation confirmed the increased expression of SPOCK2 in the endothelial cells of cecal ligation and puncture-induced septic mice. Furthermore, in vitrostudies showed that deletion of Spock2 significantly increased LPS-induced apoptosis and necrosis in human umbilical vein endothelial cells. In conclusion, SPOCK2 expression was increased in septic cardiac endothelial cells and LPS-induced human umbilical vein endothelial cells and may play a protective role.

Endothelial Cell Apoptosis but Not Necrosis Is Inhibited by Ischemic Preconditioning.

This study aimed to assess the influence of ischemic preconditioning (IP) on hypoxia/reoxygenation (HR)-induced endothelial cell (EC) death. Human umbilical vein endothelial cells (HUVECs) were subjected to 2 or 6 h hypoxia with subsequent reoxygenation. IP was induced by 20 min of hypoxia followed by 20 min of reoxygenation. Necrosis was assessed by the release of lactate dehydrogenase (LDH) and apoptosis by double staining with propidium iodide/annexin V (PI/AV), using TUNEL test, and Bcl-2 and Bax gene expression measured using RT-PCR. In PI/AV staining, after 24 h of reoxygenation, 30-33% of EC were necrotic and 16-21% were apoptotic. In comparison to HR cells, IP reduced membrane apoptosis after 24 h of reoxygenation by 50% but did not influence EC necrosis. Nuclear EC apoptosis affected about 15-17% of EC after 24 h of reoxygenation and was reduced with IP by 55-60%. IP was associated with a significantly higher Bcl-2/Bax ratio, at 8 h 2-4 times and at 24 h 2-3 times as compared to HR. Longer hypoxia was associated with lower values of Bcl-2/Bax ratio in EC subjected to HR or IP. IP delays, without reducing, the extent of HR-induced EC necrosis but significantly inhibits their multi-level evaluated apoptosis.

Differential vascular endothelial cell toxicity of established and novel BCR-ABL tyrosine kinase inhibitors.

BCR-ABL tyrosine kinase inhibitors (TKIs) have dramatically improved survival in Philadelphia chromosome-positive leukemias. Newer BCR-ABL TKIs provide superior cancer outcomes but with increased risk of acute arterial thrombosis, which further increases in patients with cardiovascular comorbidities and mitigates survival benefits compared to imatinib. Recent studies implicate endothelial cell (EC) damage in this toxicity by unknown mechanisms with few side-by-side comparisons of multiple TKIs and with no available data on endothelial impact of recently approved TKIs or novels TKIs being tested in clinical trials. To characterize BCR-ABL TKI induced EC dysfunction we exposed primary human umbilical vein ECs in 2D and 3D culture to clinically relevant concentrations of seven BCR-ABL TKIs and quantified their impact on EC scratch-wound healing, viability, inflammation, and permeability mechanisms. Dasatinib, ponatinib, and nilotinib, the TKIs associated with thrombosis in patients, all significantly impaired EC wound healing, survival, and proliferation compared to imatinib, but only dasatinib and ponatinib impaired cell migration and only nilotinib enhanced EC necrosis. Dasatinib and ponatinib increased leukocyte adhesion to ECs with upregulation of adhesion molecule expression in ECs (ICAM1, VCAM1, and P-selectin) and leukocytes (PSGL1). Dasatinib increased permeability and impaired cell junctional integrity in human engineered microvessels, consistent with its unique association with pleural effusions. Of the new agents, bafetinib decreased EC viability and increased microvessel permeability while asciminib and radotinib did not impact any EC function tested. In summary, the vasculotoxic TKIs (dasatinib, ponatinib, nilotinib) cause EC toxicity but with mechanistic differences, supporting the potential need for drug-specific vasculoprotective strategies. Asciminib and radotinib do not induce EC toxicity at clinically relevant concentrations suggesting a better safety profile.

Effect of serum from patients with ST-segment elevation myocardial infarction on endothelial cells

Introduction and objectives Clinical and experimental studies have shown that, in patients with reperfused ST-segment elevation myocardial infarction (STEMI), abnormalities in the endothelial monolayer are initiated during ischemia but rapidly intensify upon restoration of blood perfusion to the ischemic area. We aimed to evaluate the effect of serum isolated after revascularization from STEMI patients on the degree of endothelial permeability in vitro, by promoting endothelial cell apoptosis and necrosis in vitro. We also investigated the association between the percentage of serum-induced endothelial cell apoptosis or necrosis in vitro and the extent of cardiovascular magnetic resonance (CMR)-derived parameters of reperfusion injury (edema, hemorrhage, and microvascular obstruction).Methods Human coronary artery endothelial cells were incubated with serum isolated 24 hours after revascularization from 43 STEMI patients who underwent CMR and 14 control participants. We assessed the effect of STEMI serum on activation of apoptosis and necrosis, as well as on the permeability and structure of the endothelial monolayer.Results Serum from STEMI patients increased apoptosis (P < .01) and necrosis (P < .05) in human coronary artery endothelial cells and caused increased permeability of the endothelial monolayer in vitro (P < .01), due to enlarged intercellular spaces (P < .05 vs control in all cases). Higher serum-induced necrosis was associated with greater endothelial permeability in vitro (P < .05) and with more extensive CMR-derived indices of reperfusion injury and infarct size.Conclusions Postreperfusion serum activates necrosis and apoptosis in endothelial cells and increases the degree of endothelial permeability in vitro. The more potent the necrosis-triggering effect of serum, the more deleterious the consequences in terms of the resulting cardiac structure.

Effect of serum from patients with ST-segment elevation myocardial infarction on endothelial cells

Introduction and objectivesClinical and experimental studies have shown that, in patients with reperfused ST-segment elevation myocardial infarction (STEMI), abnormalities in the endothelial monolayer are initiated during ischemia but rapidly intensify upon restoration of blood perfusion to the ischemic area. We aimed to evaluate the effect of serum isolated after revascularization from STEMI patients on the degree of endothelial permeability in vitro, by promoting endothelial cell apoptosis and necrosis in vitro. We also investigated the association between the percentage of serum-induced endothelial cell apoptosis or necrosis in vitro and the extent of cardiovascular magnetic resonance (CMR)-derived parameters of reperfusion injury (edema, hemorrhage, and microvascular obstruction). MethodsHuman coronary artery endothelial cells were incubated with serum isolated 24hours after revascularization from 43 STEMI patients who underwent CMR and 14 control participants. We assessed the effect of STEMI serum on activation of apoptosis and necrosis, as well as on the permeability and structure of the endothelial monolayer. ResultsSerum from STEMI patients increased apoptosis (P <.01) and necrosis (P <.05) in human coronary artery endothelial cells and caused increased permeability of the endothelial monolayer in vitro (P <.01), due to enlarged intercellular spaces (P <.05 vs control in all cases). Higher serum-induced necrosis was associated with greater endothelial permeability in vitro (P <.05) and with more extensive CMR-derived indices of reperfusion injury and infarct size. ConclusionsPostreperfusion serum activates necrosis and apoptosis in endothelial cells and increases the degree of endothelial permeability in vitro. The more potent the necrosis-triggering effect of serum, the more deleterious the consequences in terms of the resulting cardiac structure.

Aronia Melanocarpa Fruit Juice Ameliorates the Histopathological Changes in the Myocardium and Coronary Arteries in a Rat Metabolic Syndrome Model

Abstract Aim: The purpose of this study was to examine the effect of Aronia melanocarpa fruit juice (AMFJ) on the histology of the myocardium and coronary arteries in metabolic syndrome (MS) rats. Materials and methods: The animals were divided into five groups: control, MS, MS+AMFJ2.5, MS+AMFJ5, and MS+AMFJ10. For 10 weeks, the control group received regular rat chaw and tap water, the other groups – high-fat, high-fructose diet and 10% fructose in their drinking water to induce MS. Throughout the experiment, rats received a daily oral treatment: the control and MS groups – 10 ml/kg distilled water, the other groups – AMFJ at doses of 2.5, 5.0, and 10.0 ml/kg, respectively. At the end of the experimental period, the animals were sacrificed and tissue samples from the myocardium and coronary arteries were evaluated histologically. Results: In the MS group, degeneration of the cardiomyocytes and endothelial cell necrosis were detected. In the MS+AMFJ2.5 group, cardiomyocyte damage was decreased, the endothelium was damaged and the preserved cells were activated. In MS+AMFJ5 and MS+AMFJ10 groups, the myocardium and the endothelial layer of the coronary arteries were preserved. Conclusion: These results indicate cardio- and vasoprotective effects of the juice.

Morphometric assessment of age-related structural changes in the vessels of the microcirculatory bed of the prostate gland under conditions of ethanol intoxication

Vessels of the microcirculatory bed ensure the full trophism of the body at the level of capillary-tissue relations and are the first to respond to various functional and pathological conditions of organs. At the same time, morphological changes in prostate microvasculature with age under conditions of prolonged ethanol poisoning have been understudied. The purpose of this study was to determine the age-related remodelling of the prostate vessels of the microcirculatory bed in case of prolonged alcohol intoxication. Injection, histological, morphometric, and statistical methods were used. The microvasculature of the prostate gland of 80 sexually mature white male rats of different ages was studied, 40 animals served as controls, and 40 rats were injected daily for 28 days with a 30% ethanol solution at a dose of 20 ml/kg intragastrically. Morphometric analysis indicated that chronic ethanol poisoning in white rats significantly reduces the lumens of arterial microvessels and hemocapillaries, while expanding the venous vessels in the microcirculatory bed of the prostate gland. When venous congestion occurs, the density of microvessels decreases, and microcirculation bed is disturbed. This disruption is accompanied by atrophic, dystrophic, and necrobiotic changes in endotheliocytes, epithelial cells, muscle cells, stromal structures, infiltration, and sclerosing. Intragastric 28-day administration of a 30% ethanol solution at a dose of 20 ml/kg to laboratory mature white male rats leads to pronounced structural changes in the microvasculature of the prostate microcirculatory bed: constriction of arterioles, precapillary arterioles and hemocapillaries, dilation of the capillary venules and venules, which is complicated by significant venous haemorrhage, development of atrophy, dystrophy, necrosis of vascular endothelial cells, glandular epithelial cells, muscle cells, connective tissue structures, cellular infiltration, and sclerosis. Vessels of the microcirculatory bed play a leading role in ethanol-induced damage of prostate structures, which dominate in 24-month-old experimental animals

Potential enhancement of post-stroke angiogenic response by targeting the oligomeric aggregation of p53 protein.

Tumor suppressor gene p53 and its aggregate have been found to be involved in many angiogenesis-related pathways. We explored the possible p53 aggregation formation mechanisms commonly occur after ischemic stroke, such as hypoxia and the presence of reactive oxygen species (ROS). The angiogenic pathways involving p53 mainly occur in nucleus or cytoplasm, with one exception that occurs in mitochondria. Considering the high mitochondrial density in brain and endothelial cells, we proposed that the cyclophilin D (CypD)-dependent vascular endothelial cell (VECs) necrosis pathway occurring in the mitochondria is one of the major factors that affects angiogenesis. Hence, targeting p53 aggregation, a key intermediate in the pathway, could be an alternative therapeutic target for post-stroke management.

Escherichia coli-induced inflammatory responses are temperature-dependent in human whole blood ex vivo

Systemic inflammatory conditions are often associated with hypothermia or hyperthermia. Therapeutic hypothermia is used in post-cardiac arrest and some other acute diseases. There is a need for more knowledge concerning the effect of various temperatures on the acute inflammatory response. The complement system plays a crucial role in initiating the inflammatory response. We hypothesized that temperatures above and below the physiologic 37 °C affect complement activation and cytokine production ex vivo. Lepirudin-anticoagulated human whole blood from 10 healthy donors was incubated in the presence or absence of Escherichia coli at different temperatures (4 °C, 12 °C, 20 °C, 33 °C, 37 °C, 39 °C, and 41 °C). Complement activation was assessed by the terminal C5b-9 complement complex (TCC) and the alternative convertase C3bBbP using ELISA. Cytokines were measured using a 27-plex assay. Granulocyte and monocyte activation was evaluated by CD11b surface expression using flow cytometry. A consistent increase in complement activation was observed with rising temperature, reaching a maximum at 41 °C, both in the absence (C3bBbP p < 0.05) and presence (C3bBbP p < 0.05 and TCC p < 0.05) of E. coli. Temperature alone did not affect cytokine production, whereas incubation with E. coli significantly increased cytokine levels of IL-1β, IL-2, IL-6, IL-8, IFN-γ, and TNF at temperatures > 20 °C. Maximum increase occurred at 39 °C. However, a consistent decrease was observed at 41 °C, significant for IL-1β (p = 0.003). Granulocyte CD11b displayed the same temperature-dependent pattern as cytokines, with a corresponding increase in endothelial cell apoptosis and necrosis. Thus, blood temperature differentially determines the degree of complement activation and cytokine release.

The effect of a drug Cisplatin and Thymoquinone material in the liver of rats after the induced of cancer in laboratary

Cisplatin drug is one of platinum compounds and it is in common use world wide for the treatment of a variety of human neoplasms. However in high doses it can produceundesirable toxic side effects on liver, so in this study we investigated whether Thymoqunion has protective effect on hepatotoxicity induced by cisplatin or not. Four equal-sized groups(four rats each) of adult female rats with colon cancer induced in two group unless control group by used azoxymethane carcinogen were used as (control group, AOM group cisplatin group, Thymoqunion group (TQ)). It was detected for tumor by measuring the concentration CEA in serum, it was observed significant increase (P&lt;0.05) when injected article carcinogen totals compared with the control group. when the transaction ad these two articles focusing decreased response to treatment user. Histological examination of livers were carried out using light microscopy. Results showed that cisplatin produced histopathological changes in liver tissue, congestion and expansion of central veins, dilatation and congestion of sinusoids, with necrosis of liver cells and endothelial cells, severe fatty infiltration and necrotic foci in large areas from liver cells, congestion of sinusoids, while Thymoqunion not appear any side effect on liver tissue

Lichen sclerosus: A C5B-9 mediated chronic microvascular injury syndrome potentially reflective of common adult comorbidities

Lichen sclerosus (LS) is a cutaneous disease of unknown etiology that often involves the vulva or foreskin but also can affect extragenital sites. Regardless of the anatomic site, the histomorphology and presumably pathogenesis are similar. Perhaps a clue to the pathophysiology of LS lies in its frequent association with morphea, specifically, when occurring in an extragenital context. In our experience a striking feature evident in established lichen sclerosis (LS) is one of superficial vascular drop out whereby residual vessels exhibited endothelial cell necrosis and microvascular basement membrane zone thickening, the latter reflective of antecedent episodes of microvascular injury. We sought to understand the pathophysiology that underlies the distinct vascular changes and in doing so, shed light on the pathogenesis of LS. We examined 44 cases of LS over a period of 2019 to 2021. We were able to obtain past medical histories in 34 of the 44 cases. Regarding pathological assessment, the predominant focus was on microvascular changes. We assessed the role of C5b-9 mediated vascular injury in the pathogenesis of the vasculopathy and enhanced type I interferon signaling in vessels given the morphologic semblance to the select interferonopathy syndromes, namely fibrosing dermatomyositis and Kohlmeier Degos disease. We examined the expression of CMV DNA and protein based on prior observations in an earlier study that isolated early protein expression in the microvasculature in the setting of LS and scleroderma. From a clinical perspective, the most striking association was an older age at the time of diagnosis (mean age of 62 years and median age of 61.5 years) and the presence of vascular comorbidities of diabetes, hypertension, and hyperlipidemia in almost 80% of cases. All cases showed significant microvascular changes in the superficial corium with the most frequent findings being those of significant basement membrane zone reduplication and vascular drop out. A number of cases showed prominent microvascular deposits of C5b-9 in the zone of hyalinizing fibrosis or subjacent to the discernible table of fibroplasia in the absence of enhanced type I interferon signaling. In no case were there viral cytopathic changes associated with CMV affecting the endothelium. The studies that encode CMV DNA or protein did not show a significant role for CMV reactivation in endothelium in the majority of the studied cases. It is concluded that the pathophysiology of LS includes a microvascular injury syndrome within the papillary dermis. The mechanism of endothelial cell injury is complement mediated at least in part and could reflect an adaptive immune response targeting endothelium indicative of classic complement pathway activation when coexisting with morphea or occurring in younger individuals. A non-immune based endothelial dysfunction and complement mediated injury unrelated to antibody driven classic complement pathway activation are more likely pathogenetically in the setting of certain diseases like diabetes mellitus and hypertension. Vascular drop out can be explained by the diminished endothelial progenitor pool needed to repopulate the damaged microvessels in certain settings like hypertension and diabetes.

Platelet-derived microparticles stimulated by anti-β2GPI/β2GPI complexes induce pyroptosis of endothelial cells in antiphospholipid syndrome

Platelet microparticles (PMPs) are vesicles that are released by platelets into the extracellular space and play a role in antiphospholipid antibody syndromes. PMPs have recently been recognized as a new and viable cell. There is growing evidence that the anti-β2 glycoprotein (GPI)/β2GPI complex is associated with aberrant activation of PMPs. Although studies suggest that aberrant activation of PMPs may lead to inflammatory necrosis of endothelial cells, the underlying mechanisms remain unclear. We found that although the difference in the number of PMPs was not statistically significant, NLR family pyrin domain containing 3 (NLRP3) within PMPs was increased during stimulation of anti-β2GPI/β2GPI complexes. Furthermore, we demonstrated that anti-β2GPI/β2GPI complex-induced PMPs effectively stimulated endothelial cell pyroptosis via the NLRP3/nuclear factor (NF)-κB/gasdermin D (GSDMD) signaling pathway as well as the NLRP3/Caspase-1 signaling pathway. Additionally, inhibition of NLRP3 expression in PMPs effectively reduced the inflammatory response and pyroptosis in endothelial cells. Our data suggest that PMPs aberrantly activated by anti-β2GPI/β2GPI complexes play a vital role in endothelial cell pyroptosis, and these studies provide major insights into the mechanisms of thrombosis during the treatment of antiphospholipid antibody syndrome.

Regulation of NETosis and Inflammation by Cyclophilin D in Myeloperoxidase-Positive Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is pathologically characterized by focal fibrinoid necrosis, in which ANCA-mediated neutrophil extracellular trap (NET) formation and subsequent endothelial cell necrosis occur. Cyclophilin D (CypD) plays an important role in mediation of cell necrosis and inflammation via the opening of mitochondrial permeability transition pores. This study was undertaken to examine the role of CypD in AAV pathogenesis. We assessed the role and mechanism of CypD in ANCA-stimulated neutrophils in vitro by immunostaining and electron microscopy observation. We performed a comprehensive RNA-sequencing analysis on ANCA-treated murine neutrophils. To investigate the role of CypD in vivo, we assessed disease features in CypD-knockout mice and wild-type mice using 2 different murine AAV models: anti-myeloperoxidase IgG transfer-induced AAV and spontaneous AAV. In vitro experiments showed that pharmacologic and genetic inhibition of CypD suppressed ANCA-induced NET formation via the suppression of reactive oxygen species and cytochrome c release from the mitochondria. RNA-sequencing analyses in ANCA-treated murine neutrophils revealed the involvement of inflammatory responses, with CypD deficiency reducing ANCA-induced alterations in gene expression. Furthermore, analyses of upstream regulators revealed the relevance of intracellular calcium (CypD activator) and cyclosporin (CypD inhibitor) in ANCA stimulation, indicating that the CypD-dependent opening of mitochondrial permeability transition pores is associated with ANCA-induced neutrophil activation and NETosis. In both AAV mouse models, the genetic deletion of CypD ameliorated crescentic glomerulonephritis via the inhibition of CypD-dependent neutrophil and endothelial necrosis. CypD targeting is a novel and specific therapeutic strategy for AAV via the resolution of necrotizing vasculitis.

Benefits of Ginger as Medicine for COVID-19: Literature Study

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) affects other systems, including the digestive, circulatory, urogenital, and even the central nervous systems, as its receptor Angiotensin-Converting Enzyme-2 (ACE-2) is expressed in several organs, such as lungs, intestine, heart, esophagus, kidneys, bladder, testes, liver and brain. Different mechanisms, in particular, massive virus replication, extensive apoptosis and necrosis of lung-related epithelial and endothelial cells, vascular leakage, hyperinflammatory responses, overproduction of proinflammatory mediators, cytokine storm, oxidative stress, the downregulation of ACE2 and impairment of the renin-angiotensin system contribute to the pathogenesis of COVID-19. Currently, COVID-19 is a global pandemic with no specific antiviral treatment. The favorable abilities of ginger were indicated in patients suffering from osteoarthritis, neurodegenerative disorders, rheumatoid arthritis, type 2 diabetes, respiratory distress, liver diseases, and primary dysmenorrhea. Ginger or its compounds exhibited strong anti-inflammatory and antioxidant influences in numerous animal models. This review provides evidence regarding the potential effects of ginger against SARS-CoV-2 infection and highlights its antiviral, anti-inflammatory, antioxidant, and immunomodulatory impacts in an attempt to consider this plant as an alternative therapeutic agent for the treatment of COVID-19.

α-Lipoic Acid-Plus Ameliorates Endothelial Injury by Inhibiting the Apoptosis Pathway Mediated by Intralysosomal Cathepsins in an In Vivo and In Vitro Endothelial Injury Model.

α-Lipoic acid-plus (LAP), an amine derivative of α-lipoic acid, has been reported to protect cells from oxidative stress damage by reacting with lysosomal iron and is more powerful than desferrioxamine (DFO). However, the role of LAP in experimental carotid artery intimal injury (CAII) has not yet been well investigated. Therefore, we sought to uncover the role and potential endovascular protective mechanisms of LAP in endothelial injury. In vitro, oxyhemoglobin (OxyHb) stimulation of cultured human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, balloon compression injury of the carotid artery was used to establish a rat CAII model. We found that the protein levels of cathepsin B/D, ferritin, transferrin receptor (TfR), cleaved caspase-3, and Bax increased in the injured endothelium and HUVECs but were rectified by DFO and LAP treatments, as revealed by western blotting and immunofluorescence staining. Additionally, DFO and LAP decreased oxidative stress levels and endothelial cell necrosis of the damaged endothelium. Moreover, DFO and LAP significantly ameliorated the increased oxidative stress, iron level, and lactic dehydrogenase activity of HUVECs and improved the reduced HUVEC viability induced by OxyHb. More importantly, DFO and LAP significantly reduced mitochondrial damage and were beneficial for maintaining lysosomal integrity, as indicated by acridine orange (AO), Lyso-Tracker Red, JC-1, and ATPB staining in HUVECs. Finally, LAP might offer more significant endovascular protective effects than DFO. Our data suggested that LAP exerted endovascular protective effects by inhibiting the apoptosis signaling pathway mediated by intralysosomal cathepsins by reacting with excessive iron in endothelial lysosomes after intimal injury.

3-Bromofluoranthene-induced cardiotoxicity of zebrafish and apoptosis in the vascular endothelial cells via intrinsic and extrinsic caspase-dependent pathways

Fluoranthene, a high-molecular-weight polycyclic aromatic hydrocarbon (PAH), is widely present in air pollutants, including fine inhalable particulate matter. 3-Bromofluoranthene (3-BrFlu), which is a brominated fluoranthene and halogenated PAH, is generated from waste combustion, metallurgical processes, cement production, e-waste dismantling, and photoreaction. Vascular endothelial cells have key functions in the homeostasis and the development of the cardiovascular system. The zebrafish model has been widely employed to study cardiotoxicity and embryotoxicity. However, no evidence has indicated that 3-BrFlu induces cytotoxicity in vascular endothelial cells, or cardiotoxicity and embryotoxicity in zebrafish. In this study, 3-BrFlu induced concentration-dependent changes in embryo- and cardiotoxicity. Cytotoxicity was also induced by 3-BrFlu in a concentration-dependent manner through apoptosis and necrosis in vascular endothelial cells, SVEC4-10 cells. The activities of caspase-3, -8, and -9 were induced by 3-BrFlu via an intrinsic pathway constituting Bcl-2 downregulation, Bad upregulation, and mitochondrial dysfunction; the extrinsic pathway included the expression of death receptors, including tumour necrosis factor α and Fas receptors. These results indicated that 3-BrFlu caused cardio- and embryotoxicity in zebrafish through vascular endothelial cells cytotoxicity resulting from caspase-dependent apoptosis through intrinsic and extrinsic pathways.

A broad spectrum of posterior reversible encephalopathy syndrome - a case series with clinical and paraclinical characterisation, and histopathological findings

BackgroundPosterior reversible encephalopathy syndrome (PRES) is clinical-neuroradiologically defined and potentially reversible, so there are limited data about histopathological findings. We aimed to describe the clinical and paraclinical features of patients with PRES with regard to its reversibility.MethodsThis retrospective case series encompasses 15 PRES cases out of 1300 evaluated patients from a single German center between January 1, 2010, and June 15, 2020. PRES was established according to the diagnostic criteria as proposed by the Berlin PRES Study 2012. One of the cases studied was subject to brain autopsy.ResultsFrom the 15 patients studied (median age 53 years, range 17–73; 11 female), 67 % presented with epileptic seizures, 40 % suffered from encephalopathy with reduced consciousness and 53 % developed delirium, while 47 % had headache and visual disturbances. Subcortical brain MRI abnormalities related to PRES were observed in all patients. One patient developed spinal ischemia and another Guillain-Barré syndrome in addition to PRES. Hypertensive blood pressure was the main underlying/trigger condition in all patients. Clinical symptoms and MRI changes were not reversible in 42 %, even progressive in 3 out of these 5 patients. Median time from symptom onset to diagnosis in these non-reversible cases was 7 days (range 0–13), while the median delay in diagnosis in the reversible group was 1 day (range 0–3). Cerebellar/brain stem involvement and status epilepticus were more frequently in patients with non-reversible disease course. Mortality due to PRES occurred in 13 % of these patients. Neuropathological examination of the brain of a 57-year-old female patient revealed major leukencephalopathic changes, fibrinoid necrosis of endothelial cells and fresh petechial hemorrhages in accordance with PRES.ConclusionsOur case series demonstrates that PRES was not reversible in 42 % of the studied patients. Delay in diagnosis seems to contribute to limited reversibility and poor outcome.

Pathological findings of Chinese sucker (Myxocyprinus asiaticus) infected with virulent Aeromonas hydrophila

A highly virulent strain of Aeromonas hydrophila (vAh) has caused the motile Aeromonas septicemia (MAS) in Chinese sucker (Myxocyprinus asiaticus). The pathology of MAS in Chinese sucker has not been studies well yet. Thus, the aim of this study was to determine histopathological and ultrastructural changes in Chinese sucker following vAh challenge. Histopathological examination revealed hemorrhage, hemolysis, endothelial cell damage, necrosis, cell vacuolation, lymphocyte infiltration and MMCs response. The ultrastructure showed severe tissue destruction, such as the malformation of glomerulus filtration device in trunk kidney, macrophages with large phagocytic vacuoles in head kidney, reticular cells and endothelial cells necrosis in spleen, the disappearing of glycogen and the degeneration of the diss space in liver. In conclusion, these results indicated that vAh infection would lead to serious pathological changes in tissues, which maybe results in death by anoxia, energy shortage and metabolic waste accumulation. Moreover, we found that MMCs in tissues might play an important role in fighting vAh infection, which would provide a new perspective for studies on the pathomechanism and enrich the histopathological data on MAS.