The Mitochondrial Antioxidant Sirtuin3 Cooperates with Lipid Metabolism to Safeguard Neurogenesis in Aging and Depression

Neural stem cells (NSCs), crucial for memory in the adult brain, are also pivotal to buffer depressive behavior. However, the mechanisms underlying the boost in NSC activity throughout life are still largely undiscovered. Here, we aimed to explore the role of deacetylase Sirtuin 3 (SIRT3), a central player in mitochondrial metabolism and oxidative protection, in the fate of NSC under aging and depression-like contexts. We showed that chronic treatment with tert-butyl hydroperoxide induces NSC aging, markedly reducing SIRT3 protein. SIRT3 overexpression, in turn, restored mitochondrial oxidative stress and the differentiation potential of aged NSCs. Notably, SIRT3 was also shown to physically interact with the long chain acyl-CoA dehydrogenase (LCAD) in NSCs and to require its activation to prevent age-impaired neurogenesis. Finally, the SIRT3 regulatory network was investigated in vivo using the unpredictable chronic mild stress (uCMS) paradigm to mimic depressive-like behavior in mice. Interestingly, uCMS mice presented lower levels of neurogenesis and LCAD expression in the same neurogenic niches, being significantly rescued by physical exercise, a well-known upregulator of SIRT3 and lipid metabolism. Our results suggest that targeting NSC metabolism, namely through SIRT3, might be a suitable promising strategy to delay NSC aging and confer stress resilience.

PROTECTIVE ACTIVITY OF LEMNA MINOR L. IN CHRONIC BLEOMYCIN–INDUCED LUNG INFLAMMATION

This research investigates the probable effects of induced chronic (28 days) lung inflammations by Bleomycin (BLM) and its oxidative-toxicity protection by the aquatic extract of Lemna minor L. (LME). Balb/c male mice were in every two days exposed to: (1) a controlled normal diet, (2) an LME treatment (120 mg/kg bwt, i.p.), (3) a BLM treatment (0.34 U/kg bwt, i.p.), and (4) an LME (120 mg/kg bwt, i.p.) administered two hours prior to the BLM. At the 30 experimental days of chronic BLM administration, the mice were sacrificed and fresh lung tissue was collected for biochemical determination and EPR analysis. The BLM treatment significantly increased the biochemical indices two-fold (SOD, CAT, MDA, TC) than controls. Furthermore, lung/alveolar cell experiments were performed to investigate the LME modulative and oxidative-protection effect. The results revealed that LME alone and in combination (LME + BLM) inhibited BLM expression by significantly reducing EPR-ascorbate (p < 0.05), ROS production (p < 0.05), and by enhancing enzymatic antioxidants. As a conclusion, our results indicated that chronic BLM toxicity and lung inflammation could be neutralized by long-term LME treatment. Therefore, LME + BLM prevented the detrimental impacts of BLM and have proved to have a potential therapeutic effect on the oxidative stress biomarkers, antioxidant enzymes and alleviation of lung inflammations.

Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis

Background and Aims: Ulcerative colitis(UC) is a chronic inflammatory bowel disorder with highly cellular heterogeneity. Mass cytometry(Cy-TOF) and single-cell RNA sequencing (scRNA-seq) have revealed cellular heterogeneity of UC. However, comprehensive elucidation of tissue topological changes within the UC ecosystem is still missing. And we aimed to illustrate compositional and spatial changes of the UC ecosystem.Methods: Imaging mass cytometry (IMC) and scRNA-seq were applied to depict the single-cell landscape of colon ecosystem.Results: We noticed tissue topological changes featured with macrophage disappearance reaction (MDR) in UC region. MDR only occurred for CD163+ tissue-resident macrophages. We found reactive oxygen species (ROS) level were higher in UC region but ROS scavenging enzyme SOD1/2 were barely detected in resident macrophages, resulting selective oxidative protection for inflammatory macrophages and resident macrophage disappearance reaction. Furthermore, inflammatory macrophages replaced resident macrophages during UC, which played a key role in forming the inflammatory cellular network by producing TNF-α and IL-1β. Conclusions: Our study dissected the microenvironment of UC lesions at single-cell resolution while preserving its architecture, based on which, we discovered the mechanism of MDR in UC region and resident macrophage specific MDR resulted in infiltration of inflammatory macrophage, which formed the cytokine producing network within the local cellular neighborhood.

Fluorometric Optimized Determination of Total Glutathione in Erythrocytes

Glutathione is a tripeptide natural product characterized by a non-canonical peptide bond with an amide moiety linking the nitrogen of cysteine to the γ-carboxyl of glutamate, and is found ubiquitously in nature, in animals, plants and microorganisms. One of the most abundant biological matrices is represented by erythrocytes, being glutathione the only sulfur-containing mechanism for the red blood cell oxidative protection. Several analytical methods for glutathione determination from different samples are described in the literature and most of these methods are based on the use of high-performance liquid chromatography. HPLC equipment is not available in all the biochemical laboratories, and, moreover, displays lot of economic and ecological limitations, including organic solvent consumption and time-consuming analysis. Here, an organic-free high-throughput fluorometric methodology for the analysis of total glutathione in erythrocytes is reported, avoiding the use of time-consuming and not-sustainable techniques.

Impact of Dry Hopping on Beer Flavor Stability

To investigate the chemical and sensorial impact of dry hopping time on typical pale ale, a standardized beer was produced and separated into ten vessels. Nine vessels were dry hopped, and one vessel remained un-hopped as a control. Impact of dry hopping contact time was investigated over 96 h. Polyphenols and iso-α-acid t/c ratio were analyzed in both Young and Aged beer samples. Total polyphenol content generally increased in both young and aged treatments compared to controls. Analysis of the t/c ratio suggests that both Young and Aged beers were chemically preserved to some degree after approximately 12 h at the given dry hopping rate regardless of age. Within the Aged beer trials, 96 h of dry hop contact yielded a significant increase in t/c ratio compared to all other Aged trials. This suggests that a 4-day dry hop regime may yield additional oxidative protection of iso-α-acids in beers stored unrefrigerated for 30 days. Descriptive analysis was also performed with an 8-person, trained panel; however, beers were sensorially distinguished by their aging time as opposed to their dry hopping time.

Effects of the Reactive Moiety of Phenolipids on Their Antioxidant Efficiency in Model Emulsified Systems

Our previous research was focused on the effects of hydrophobicity on the antioxidant (AO) efficiency of series of homologous antioxidants with the same reactive moieties. In this work we evaluate the antioxidant efficiency of hydrophobic phenolipids in 4:6 olive oil-in-water emulsions, with different phenolic moieties (derived from caffeic, 4-hydroxycinnamic, dihydrocaffeic acids, tyrosol and hydroxytyrosol), with alkyl chains of 8 and 16 carbons, and compare the antioxidant efficiency with that of the parent compounds. All catecholic phenolipids, in particular the C8 derivatives, have proven to be better antioxidants for the oxidative protection of emulsions than their parental compounds with octyl dihydrocafffeate being the most efficient (16-fold increase in relation to the control). To understand the importance of some factors on the antioxidant efficiency of compounds in emulsions, Pearson’s correlation analysis was carried out between antioxidant activity and the first anodic potential (Epa), reducing capacity (FRAP value), DPPH radical scavenging activity (EC50) and the concentration of antioxidants in each region of the emulsified system. Results confirm the importance of the effective concentration of AOs in the interfacial region (AOI) (ρ = 0.820) and of the Epa (ρ = −0.677) in predicting their antioxidant efficiency in olive oil-in-water emulsions.

Impact of curcumin on replicative and chronological aging in the Saccharomyces cerevisiae yeast

Curcumin is a biologically active compound of vegetable origin which has a hormetic effect. Pro-health and anti-aging properties of curcumin have been known for years. The main benefit of curcumin is thought to be its anti-oxidative action. Despite vast amount of data confirming age-delaying activity of curcumin in various groups of organisms, so far little has been discovered about curcumin’s impact on cell aging in the experimental model of the Saccharomyces cerevisiae budding yeast. We have been able to demonstrate that curcumin significantly increases oxidative stress and accelerates replicative and chronological aging of yeast cells devoid of anti-oxidative protection (with SOD1 and SOD2 gene deletion) and deprived of DNA repair mechanisms (RAD52). Interestingly, curcumin delays aging, probably through hormesis, of the wild-type strain BY4741.