Centenarians-the way to healthy vascular ageing and longevity: a review from VascAgeNet.

The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is reduced in healthy centenarians along with late onset of age-related diseases compared with the general aged population.

Unraveling host genetics and microbiome genome crosstalk: a novel therapeutic approach.

The ability of the gut microbiome to adapt to a new environment and utilize a new metabolite or dietary compound by inducing structural variations (SVs) in the genome has an important role in human health. Here, we discuss recent data on host genetic regulation of SV induction and its use as a new therapeutic approach.

Protocol for the induction of innate immune memory in human smooth muscle cells and endothelial cells in vitro.

Non-immune cells, like innate immune cells, can develop a memory-like phenotype in response to priming with microbial compounds or certain metabolites, which enables an enhanced response to a secondary unspecific stimulus. This paper describes a step-by-step protocol for the induction and analysis of trained immunity in human endothelial and smooth muscle cells. We then describe steps for cell culture with cryopreserved vascular cells, subcultivation, and induction of trained immunity.

LXRα Regulates oxLDL-Induced Trained Immunity in Macrophages.

Reprogramming of metabolic pathways in monocytes and macrophages can induce a proatherosclerotic inflammatory memory called trained innate immunity. Here, we have analyzed the role of the Liver X receptor (LXR), a crucial regulator of metabolism and inflammation, in oxidized low-density lipoprotein (oxLDL)-induced trained innate immunity. Human monocytes were incubated with LXR agonists, antagonists, and oxLDL for 24 h.

Targeting inflammation with collagen.

Tissue damage caused by an infection oran autoimmune disease triggers degradation of collagen in the extracellular matrix (ECM), which further enhances inflammation. Therefore, improving ECM in aninflamed tissue can be exploited as a potential therapeutic target. A recentstudy emphasised an innovative approach against COVID-19 using polymerised type I collagen (PTIC) that improves disease severity through a hitherto unknownmechanism.

LDL-C augments whereas HDL-C prevents inflammatory innate immune memory.

Recent studies emphasize the importance of low-density lipoprotein cholesterol (LDL-C) in altering the hematopoietic cell compartment of bone marrow and of high-density lipoprotein cholesterol (HDL-C) in inhibiting metabolic endotoxemia-induced inflammation. The data suggest that these lipoproteins may exert their inflammatory or anti-inflammatory roles by modulating innate immune memory. Targeting specific LDL-C and HDL-C subfractions could therefore potentially reduce the residual risk in hepatic and cardiometabolic disease.

Synthesis and in vitro evaluation of cyclodextrin hyaluronic acid conjugates as a new candidate for intestinal drug carrier for steroid hormones.

Steroid hormones became increasingly interesting as active pharmaceutical ingredients for the treatment of endocrine disorders. However, medical applications of many steroidal drugs are inhibited by their very low aqueous solubilities giving rise to low bioavailabilities. Therefore, the prioritized oral administration of steroidal drugs remains problematic.

Reversible immobilization of a protein to a gold surface through multiple host-guest interactions.

Monolayers were formed by specific interactions between adamantylated proteins (transferrin, lysozyme) and a β-cyclodextrin (β-CD) monolayer on a gold surface. Very high stabilities could be reached by multiple interactions of 3-6 adamantyl moieties linked through triethylene glycol spacers to the protein with β-CD rings attached to the surface. Furthermore, bound proteins could be completely removed from the surface through competitive binding of an excess of free adamantane.

Solubilizing steroidal drugs by β-cyclodextrin derivatives.

Administration of steroidal drugs is hampered by their very low solubilities in water. β-Cyclodextrin and β-cyclodextrin derivatives can solubilize steroids and improve bio-availability of these hydrophobic APIs. A systematic overview of the achievable solubility enhancements of various steroids, testosterone, estradiol, progesterone, hydrocortisone, prednisone, dexamethasone, and finasteride, is provided.

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs.

Methyl and ethyl thioether groups were introduced at all primary positions of α-, β-, and γ-cyclodextrin by nucleophilic displacement reactions starting from the corresponding per-(6-deoxy-6-bromo)cyclodextrins. Further modification of all 2-OH positions by etherification with iodo terminated triethylene glycol monomethyl ether (and tetraethylene glycol monomethyl ether, respectively) furnished water-soluble hosts. Especially the β-cyclodextrin derivatives exhibit very high binding potentials towards the anaesthetic drugs sevoflurane and halothane.