Showing papers by "Carlo Cervellati published in 2023"
TL;DR: In this article , the role of HDL lipoprotein and ceramides in cerebrovascular diseases and the repercussion on vascular dementia was highlighted and an up-to-date picture of the impact of saturated and omega-3 fatty acids on HDL circulating levels, functionality and ceramide metabolism was provided.
Abstract: Cerebrovascular diseases and the subsequent brain hypoperfusion are at the basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels of triglycerides and LDL-cholesterol and a parallel decrease in HDL-cholesterol, in turn, is pivotal in promoting atherosclerosis which represents a common feature of cardiovascular and cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from a cardiovascular and a cerebrovascular prospective. However, emerging evidence suggests that their quality and functionality play a more prominent role than their circulating levels in shaping cardiovascular health and possibly cognitive function. Furthermore, the quality of lipids embedded in circulating lipoproteins represents another key discriminant in modulating cardiovascular disease, with ceramides being proposed as a novel risk factor for atherosclerosis. This review highlights the role of HDL lipoprotein and ceramides in cerebrovascular diseases and the repercussion on vascular dementia. Additionally, the manuscript provides an up-to-date picture of the impact of saturated and omega-3 fatty acids on HDL circulating levels, functionality and ceramide metabolism.
2 citations
TL;DR: In this article , a meta-analysis of existing data comparing the PON1 arylesterase activity in AD and healthy subjects from the general population was performed, which revealed that PON 1 activity was significantly lower in the AD group compared to controls, exhibiting low level of heterogeneity.
TL;DR: This paper showed that reactive microglia, dysfunctional mitochondria, amyloid-β aggregates and pro-inflammatory cytokines, such as reactive micro-glia and reactive microcell activation, can cause cancer.
TL;DR: In this paper , the effect of nutraceutical compounds (NC) on HDL-C was investigated and it was found that the administration of an NC with beneficial effects on lipid homeostasis also positively impacts HDL function by improving the balance between protective and damaging determinants.
Abstract: BACKGROUND
In earlier studies, it has been observed that 8-week treatment with a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids and hydroxytyrosol improves lipid profile and endothelial function and reduces the level of oxidized low-density lipoprotein (oxLDL). We hypothesize that this effect might be, at least in part, explained by positive modulation exerted by the NC on the atheroprotective function of high-density lipoprotein (HDL).
AIM
This study aimed to evaluate whether the NC could influence determinants of HDL function.
METHODS
Forty-five subjects with low-moderate dyslipidaemia were enrolled and treated for 8 weeks with the NC, followed by 4 weeks of washout. Blood samples were collected at every time point to evaluate changes in lipid profile, endothelial function, oxLDL, and markers of HDL function, such as the anti-oxidant activities of paraoxonase-1, glutathione peroxidase-3 (Gpx3), lipoprotein-phospholipase A2 (Lp-PLA2), and pro-oxidant activity of myeloperoxidase (MPO).
RESULTS
Although the concentration of HDL-C did not change, the activity of Lp-PLA2 significantly decreased upon treatment (-11.6%, p<0.001) and returned to baseline level 4 weeks after the end of treatment. In contrast, Gpx3 increased after treatment (+5%, p<0.01) and remained unvaried after 4 weeks. Both MPO activity and concentration significantly decreased after the washout period (-33 and 32%, p<0.001).
CONCLUSION
For the first time, it was found that the administration of an NC with beneficial effects on lipid homeostasis also positively impacts HDL function by improving the balance between protective and damaging determinants. Further investigation is required to corroborate our findings.
TL;DR: In this article , a transglutaminase (TGase) from L. infantum was shown to be Ca2+- and GTP-dependent, corresponding to a 54 kDa protein, which was purified to homogeneity through two chromatographic steps.
Abstract: Simple Summary Protozoan parasites of the Leishmania genus (Kinetoplastida: Trypanosomatidae) are responsible for human and animal leishmaniasis, pathologies mainly spread in the tropical and subtropical regions of the Americas and Afro-Eurasia, with several millions of people affected worldwide. Antileishmanial drugs present problems associated with drug toxicity and increasing parasite resistance. Therefore, the acquirement of further knowledge of these parasites with a focus on new potential drug targets is extremely useful. While transglutaminases are known to be involved in cell death and autophagy, it appears that these functions are very important for parasites’ virulence. Transglutaminase activity has been reported in Leishmania, where it was shown to be important for the proliferation of the insect promastigote stage. However, the enzyme has never been purified or well characterized. This study aimed to fill this knowledge gap by isolating and characterizing TGase from L. infantum promastigotes. For the first time, we showed a Ca2+- and GTP-dependent TGase in Leishmania corresponding to a 54 kDa protein, which was purified to homogeneity through two chromatographic steps: DEAE-Sepharose and Heparin-Sepharose. These results might allow for the exploration of the potential of this enzyme in fighting leishmaniasis. Abstract While human and animal leishmaniasis affect several millions of people worldwide, L. infantum is the species responsible for visceral leishmaniasis in Europe, Middle East, and America. Antileishmanial drugs present issues associated with drug toxicity and increasing parasite resistance. Therefore, the study of this parasite with a focus on new potential drug targets is extremely useful. Accordingly, we purified and characterized a transglutaminase (TGase) from L. infantum promastigotes. While Tgases are known to be involved in cell death and autophagy, it appears that these functions are very important for parasites’ virulence. For the first time, we showed a Ca2+- and GTP-dependent TGase in Leishmania corresponding to a 54 kDa protein, which was purified by two chromatographic steps: DEAE-Sepharose and Heparin-Sepharose. Using polyclonal antibodies against a 50-amino-acid conserved region of the catalytic core of human TGase 2, we revealed two other bands of 66 and 75 kDa. The 54 kDa band appears to be different from the previously reported TGase, which was shown to be Ca2+- independent. Future research should address the identification of the purified enzyme sequence and, subsequently, its cloning to more comprehensively investigate its pathophysiological function and possible differences from mammal enzymes.
TL;DR: Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood-brain barrier (BBB) by regulating tight junction molecular assembly as discussed by the authors .
Abstract: Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood-brain barrier (BBB) by regulating tight junction molecular assembly.Since changes in microbiota and BBB may play a role in neurodegenerative disorders, we aimed to determine whether serum zonulin levels change in older patients affected by different types of dementia or mild cognitive impairment (MCI).We evaluated serum zonulin levels in patients with late-onset AD (LOAD), vascular dementia (VAD), MIXED (AD + VAD) dementia, amnestic MCI, and in healthy controls.Compared with controls, serum zonulin increased in LOAD, MIXED dementia, and aMCI but not in VAD, independent of potential confounders (ANCOVA p = 0.01; LOAD vs controls, p = 0.01; MIXED vs. controls, p = 0.003; aMCI vs. controls, p = 0.04). Notably, aMCI converting to dementia showed significantly higher levels of zonulin compared with stable aMCI (p = 0.04). Serum zonulin inversely correlated with the standardized Mini-Mental State Examination (MMSE) score (p < 0.05), regardless of potential confounders.We found increased serum zonulin levels in patients with aMCI, LOAD and MIXED dementia, but not in VAD; moreover, zonulin levels were higher in aMCI converting to AD compared with stable ones.Our findings suggest that a dysregulation of intestinal-epithelial barrier and/or BBB may be an early specific event in AD-related neurodegeneration.
TL;DR: Although substantial progress has been made in the last two decades, there are still important unfilled gaps in the understanding of the pathomechanism of Alzheimer's disease (AD) as mentioned in this paper .
Abstract: Although substantial progress has been made in the last two decades, there are still important unfilled gaps in the understanding of the pathomechanism of Alzheimer's disease (AD) [...].
TL;DR: In this article , the authors evaluated whether serum Lp-PLA2 activity might be an early and/or late biomarker for different forms of dementia and found a significant trend towards higher levels of Lpplipase A2 activity in vascular dementia compared with the other groups.
Abstract: A wealth of evidence suggests that Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a relevant role in atherogenesis and inflammation, which in turn are associated with the risk of developing dementia. The aim of this study was to evaluate whether serum Lp-PLA2 activity might be an early and/or late biomarker for different forms of dementia. Serum Lp-PLA2 activity was assessed in older patients with mild cognitive impairment (MCI, n = 166; median clinical follow-up = 29 months), Late-Onset Alzheimer’s disease (LOAD, n = 176), vascular dementia (VAD, n = 43), dementia characterized by an overlap between LOAD and VAD (AD-VAD MIXED dementia) (n = 136), other dementia subtypes (n = 45), and cognitively normal controls (n = 151). We found a significant trend towards higher levels of Lp-PLA2 activity in VAD compared with the other groups (ANOVA, p = 0.028). Similarly, Lp-PLA2 activity was greater in MCI converting to VAD compared with those that did not or did convert to the other types of dementia (ANOVA, p = 0.011). After adjusting for potential confounders, high levels of Lp-PLA2 activity were associated with the diagnosis of VAD (O.R. = 2.38, 95% C.I. = 1.06–5.10), but not with other types of dementia. Our data suggest that increased serum Lp-PLA2 activity may represent a potential biomarker for the diagnosis of VAD.