Elovanoid-N34 modulates TXNRD1 key in protection against oxidative stress-related diseases.

The thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This lipid mediator induces TXNRD1 structure changes that modify the FAD interface domain, leading to its activity modulation. The addition of ELV-N34 decreased membrane and cytosolic TXNRD1 activity, suggesting localizations for the targeted reductase. These results show for the first time that the lipid mediator ELV-N34 directly modulates TXNRD1 activity, underling its protection in several pathologies when uncompensated oxidative stress (UOS) evolves.

Elovanoids are neural resiliency epigenomic regulators targeting histone modifications, DNA methylation, tau phosphorylation, telomere integrity, senescence programming, and dendrite integrity.

Cellular identity, developmental reorganization, genomic structure modulation, and susceptibility to diseases are determined by epigenomic regulation by multiple signaling interplay. Here we demonstrate that elovanoids (ELVs), mediators derived from very-long-chain polyunsaturated fatty acids (VLC-PUFAs, n-3, C > 28), and their precursors in neurons in culture overcome the damage triggered by oligomeric amyloid-beta (OAß), erastin (ferroptosis-dependent cell death), or other insults that target epigenomic signaling. We uncover that ELVs counteract damage targeting histones H3K9 and H3K27 methylation and acetylation; tau hyperphosphorylation (pThr181, pThr217, pThr231, and pSer202/pThr205 (AT8)); senescence gene programming (p16INK4a, p27KIP, p21CIP1, and p53); DNA methylation (DNAm) modifying enzymes: TET (DNA hydroxymethylase), DNA methyltransferase, DNA demethylase, and DNAm (5mC) phenotype. Moreover, ELVs revert OAß-triggered telomere length (TL) attrition as well as upregulation of telomerase reverse transcriptase (TERT) expression fostering dendrite protection and neuronal survival. Thus, ELVs modulate epigenomic resiliency by pleiotropic interrelated signaling.

cRel and Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets for Neuroprotection.

Wnt5a triggers inflammatory responses and damage via NFkB/p65 in retinal pigment epithelial (RPE) cells undergoing uncompensated oxidative stress (UOS) and in experimental ischemic stroke. We found that Wnt5a-Clathrin-mediated uptake leads to NFkB/p65 activation and that Wnt5a is secreted in an exosome-independent fashion. We uncovered that docosahexaenoic acid (DHA) and its derivative, Neuroprotectin D1 (NPD1), upregulate c-Rel expression that, as a result, blunts Wnt5a abundance by competing with NFkB/p65 on the Wnt5a promoter A. Wnt5a increases in ischemic stroke penumbra and blood, while DHA reduces Wnt5a abundance with concomitant neuroprotection. Peptide inhibitor of Wnt5a binding, Box5, is also neuroprotective. DHA-decreased Wnt5a expression is concurrent with a drop in NFkB-driven inflammatory cytokine expression, revealing mechanisms after stroke, as in RPE cells exposed to UOS. Limiting the Wnt5a activity via Box5 reduces stroke size, suggesting neuroprotection pertinent to onset and progression of retinal degenerations and stroke consequences. NPD1 disrupts Wnt5a feedback loop at two sites: (1) decreasing FZD5, thus Wnt5a internalization, and (2) by enhancing cREL activity, which competes with p65/NFkB downstream endocytosis. As a result, Wnt5a expression is reduced, and so is its inflammatory signaling in RPE cells and neurons in ischemic stroke.

Sulfitobacter faviae sp. nov., isolated from the coral Faviaveroni.

Three closely related, non-sporulating, aerobic, Gram-stain-negative, motile, rod-shaped isolates (S5-53T, S6-62 and S6-64) were obtained from mucus of corals Favia veroni from the Andaman Sea, India. Colonies grown on marine agar were small, circular and cream-coloured. Heterotrophic growth was observed at 10-40 °C and pH 6-10; optimum growth occurred at 25-30 °C and pH 7-8. 16S rRNA gene sequence analysis confirmed the isolates belonged to the genus Sulfitobacter and the three isolates shared more than 99 % pairwise sequence similarity. Strain S5-53T shared highest 16S rRNA gene sequence similarity of 98.43 % with Sulfitobacter dubius KMM 3554T. DNA-DNA relatedness among the three isolates was above 70 % whereas strain S5-53T showed less than 70 % relatedness with the type strains of closely related species. The DNA G+C content of strain S5-53T was 61 mol%. It contained phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and diphosphatidylglycerol as major polar lipids. Predominant fatty acids included C18 : 1ω7c, C18 : 1ω7c 11-methyl, C16 : 0 and C10 : 0 3-OH. Q10 was the major respiratory quinone. Based on this polyphasic analysis, the new isolates (S5-53T, S6-62 and S6-64) are considered to represent a novel species of the genus Sulfitobacter, for which the name Sulfitobacter faviae sp. nov. is proposed. The type strain is S5-53T(=JCM 31093T=LMG 29156T).

Is Vibrio fluvialis emerging as a pathogen with epidemic potential in coastal region of eastern India following cyclone Aila?

An isolated area with diarrhoea epidemic was explored at Pakhirala village of the Sundarbans, a coastal region of South 24 Parganas district of West Bengal, eastern India. The Pakhirala village was surrounded by other villages affected by a similar epidemic. The affected villages experienced this epidemic following the cyclone Aila, which had hit the coastal region of the Sundarbans in eastern India. In Pakhirala, the situation was the worst. Within a span of six weeks (5 June-20 July 2009), 3,529 (91.2%) of 3,871 residents were affected by watery diarrhoea. Of all the cases (n = 3,529), 918 (26%) were affected by moderate to severe diarrhoea. In other villages, 28,550 (70%) of the 40,786 people were affected; of them, 3,997 (14%) had moderate to severe watery diarrhoea. The attack rate and the severity of the cases were significantly higher in Pakhirala village compared to other affected villages. The laboratory results revealed that Vibrio fluvialis was the predominant pathogen in Pakhirala village (5 of 6 laboratory-confirmed organisms) whereas Vibrio cholerae O1 Ogawa was the predominant pathogen in other villages of Gosaba block (7 of 9 bacteriologically-confirmed organisms). This result indicates that V fluvialis behaves more aggressively than V cholerae O1 in an epidemic situation with a higher attack rate and a different clinical picture. An in-depth study is required to explore its pathogenicity in detail, geographical distribution, and possible control measures, including development of specific vaccine preparation and determination of its efficacy.