could someone please provide a sufficient explanation about the difference between the epithelial and the endothelial cells in terms of location/main purpose or function?

https://doi.org/10.12182/20211160202

https://pubmed.ncbi.nlm.nih.gov/34841761

Abstract

Objective

To investigate the regulatory function and mechanism of β-hydroxybutyrate (β-OHB), a ketone body, on the mitochondrial oxidative stress of inflammatory human umbilical vein endothelial cells (HUVECs).

Methods

Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were used to induce macrophages to release proinflammatory factors, and the culture supernatant was collected as a macrophage-conditioned medium (MCM) to culture HUVECs. A total of 7 groups of cells were used in the study: ①control group, or normal cultured HUVECs, ②MCM group, or the MCM-cultured HUVECs, groups ③ to ⑦ were all HUVECs co-cultured with different reagents, including ③MCM β-OHB group, ④MCM N-acetylcysteine (NAC) group, ⑤MCM β-OHB NAC group, ⑥MCM β-OHB histone deacetylase agonist ITSA1 group, and ⑦MCM β-OHB histone deacetylase inhibitor Entinostat group. MitoSOX immunofluorescence staining was conducted to analyzes the mitochondrial superoxide levels, real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was performed to examine the mRNA expression of antioxidant genes, and Seahorse mitochondrial energy analyzer was used to measure mitochondrial aerobic respiration capacity.

Results

Compared with the control group, mitochondrial superoxide production was significantly increased in the MCM cultured HUVECs cells, while β-OHB treatment significantly inhibited mitochondrial superoxide production, which was accompanied by an increase in the mRNA expression of antioxidant genes, and significant increase in the basal mitochondrial oxygen consumption rate and respiratory reserve capacity. NAC treatment did not further enhance the protective effect of β-OHB on mitochondrial functions. In addition, ITSA1 treatment could completely offset the antioxidant and mitochondrial protective effects of β-OHB, and these stated effects were still maintained after Entinostat treatment.

Conclusion

The ketone body β-OHB attenuates the mitochondrial oxidative stress of vascular endothelial cells through activating the antioxidant pathway and inhibiting histone deacetylase activity.

" Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected and that the main protease of SARS-CoV-2 (Mpro) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, Mpro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood–brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the Mpro-induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19... "

https://www.nature.com/articles/s41593-021-00926-1

necroptosis ->

1 Definition

Necroptosis is a programmed form of necrosis. It is morphologically similar to necrosis, but unlike necrosis, it is initiated or controlled by cellular signaling cascades, as is apoptosis.

2 Background

Necroptosis is mainly relevant in the context of immune response and inflammatory processes. Among other things, it is used as a defense mechanism in viral infections. Here, it allows the cell to undergo caspase-independent cell death in the presence of viral caspase inhibitors.

3 Biochemistry

Necroptosis is based on a multistep signaling pathway. Initially, TNFα leads to stimulation of the TNF receptor TNFR1. The TNFR-associated death protein TRADD binds to TNFR1, which, together with TRAF2, activates the serine/threonine kinase RIPK1. The latter in turn recruits RIPK3 and leads to the formation of a necrosome (ripoptosome). The necrosome phosphorylates the pseudokinase MLKL, which leads to an increase in permeability of the cell membrane.

[https://flexikon.doccheck.com/de/Nekroptose?utm_source=www.doccheck.flexikon&utm_medium=web&utm_campaign=DC%2BSearch](https://flexikon.doccheck.com/de/Nekroptose?utm_source=www.