Journal: Advanced Science

Article Title: Aberrant Mitochondrial Metabolism in Alzheimer's Disease Links Energy Stress with Ferroptosis

doi: 10.1002/advs.202504175

Figure Lengend Snippet: ATP is linked to GSH synthesis revealing ferroptosis vulnerability under energy stress. a) Schematic displaying that two ATP molecules generated by the electron transport chain (ETC) are required to synthesise 1 GSH molecule; γ‐GCS, γ‐glutamylcysteine synthetase; GS, GSH synthetase. b) Time course of t‐GSH depletion with buthionine sulphoximine (BSO) in HT22 neuronal cells. c) boxplot showing t‐GSH across MAP study subjects assigned according to dementia and pathology (CERAD); each dot represents individual subject; a one way ACNOVA with age at death, APOE ε4, and sex as covariates. d) global cognition median split high versus low t‐GSH over 5 years preceding death (all subjects; n = 615). e–i) GSH recovery after 4 h of BSO treatment – GSH, ATP and viability were measured in HT22 cells after 17 h of recovery in the presence of escalating doses of ETC inhibitors (rotenone – complex 1 inhibitor; TTFA – complex II inhibitor; antimycin A – Complex III inhibitor; sodium azide – Complex IV inhibitor; CCCP – mitochondrial uncoupler). j–l) Bar plots of ATP, t‐GSH and viability after 17 h co‐treatment with 5% of either ATP‐encapsulated or empty liposomes with ETC inhibitors; antimycin (250 n m ), azide (7.5 m m ) and CCCP (3.125 µ m ). m) schematic diagram showing the action of ATP nucleosidase (Cap 17) cleaving the N‐glycosidic bond between the adenine and sugar moieties of ATP, resulting in adenosine and ribulose 5‐triphosphate products. n) bar plots of ATP and t‐GSH in HT22 cells FACS‐sorted for high transfection of Cap17 (pCap17) or empty vector (pEV). Data in j‐l & n presented as mean ± SEM of 3 independent experiments, multiple two‐sided t ‐tests, * indicates significance p <0.05. nd indicates no difference. Schematics in a & m created with BioRender.com.

Article Snippet: BSO (Cat#B251), arachidonic acid (Cat#10931) and ammonium iron(II) sulfate hexahydrate (Cat#203505), liproxstatin‐1 (LPX, Cat#SML1414), glutathione ethyl ester (Cat# G1404) were purchased from Merck.

Techniques: Generated, Liposomes, Transfection, Plasmid Preparation

Journal: Microorganisms

Article Title: Optimizing Precision Probiotics for Mitigating Graft-Versus-Host Disease

doi: 10.3390/microorganisms13040706

Figure Lengend Snippet: Oral supplementation with precision probiotics ameliorates GVHD and increases survival. ( A ) Schematic overview of the GVHD protocol used to assess probiotic efficacy in mice. Lethally irradiated Balb/C recipients underwent transplantation with 2 × 10 7 C57BL/6 T cell-depleted bone marrow cells and 5 × 10 6 splenic T cells. Recipients were initially treated with levofloxacin. After transplantation (day 0), mice were treated with levofloxacin in the drinking water until day +7, then clindamycin until day +10. Starting on day +11 mice were orally gavaged a probiotic cocktail (1 × 10 8 colony-forming unit of Clostridium bolteae , Ruminococcus gnavus , R. torques , Blautia producta, Bifidobacterium longum and Lactococcus lactis in 0.2 mL sterile PBS) or sterile PBS (vehicle, 0.2 mL) every 3 days for the remainder of the experiment. ( B ) Weight and ( C ) GVHD scores were monitored during the acute phase of GVHD. ( D ) Survival of GVHD mice. Statistical analysis by log-rank test. ( E ) Acetate, propionate, and butyrate concentrations in cecal contents of GVHD mice. Bars represent mean ± SEM. Points represent results from individual animals. Data are 5 mice per group from 2 experiments, final n = 10 per group. Statistical analysis by Mann–Whitney test. ** p < 0.01. **** p < 0.0001. ns, not significant.

Article Snippet: The bacterial cocktail contained Clostridium bolteae, Bifidobacterium longum, Blautia producta, Lactococcus lactis (human, ATCC 19435, strain NCTC 6681), Ruminococcus gnavus (human, ATCC 29149, strain VPI C7-9), and Ruminococcus torques (human, ATCC 27756, strain VPI B2-51), with each strain administered at 1 × 10 8 colony-forming units (CFU) in a total volume of 0.2 mL sterile PBS.

Techniques: Probiotics, Irradiation, Transplantation Assay, Sterility, MANN-WHITNEY