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- Michel, M., et al.
(författare)
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Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function
- 2022
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Ingår i: Science. - Stockholm : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1471-1476
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
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- Chng, Kern Rei, et al.
(författare)
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Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment
- 2020
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 941-951
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Tidskriftsartikel (refereegranskat)abstract
- Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections. Spatiotemporal characterization of microbial diversity and antibiotic resistance in a tertiary-care hospital reveals broad distribution and persistence of antibiotic-resistant organisms that could cause opportunistic infections in a healthcare setting.
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- Marimuthu, Kanagaraj, et al.
(författare)
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A meta-analysis of the effect of combinations of immune modulating nutrients on outcome in patients undergoing major open gastrointestinal surgery
- 2012
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 255:6, s. 1060-1068
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Forskningsöversikt (refereegranskat)abstract
- Background: Immune modulating nutrition (IMN) has been shown to reduce complications after major surgery, but strong evidence to recommend its routine use is still lacking.Objective: The aim of this meta-analysis was to evaluate the impact of IMN combinations on postoperative infectious and noninfectious complications, length of hospital stay, and mortality in patients undergoing major open gastrointestinal surgery.Methods: Randomized controlled trials published between January 1980 and February 2011 comparing isocaloric and isonitrogenous enteral IMN combinations with standard diet in patients undergoing major open gastrointestinal surgery were included. The quality of evidence and strength of recommendation for each postoperative outcome were assessed using the GRADE approach and the outcome measures were analyzed with RevMan 5.1 software (Cochrane Collaboration, Copenhagen, Denmark).Results: Twenty-six randomized controlled trials enrolling 2496 patients (1252 IMN and 1244 control) were included. The meta-analysis suggests strong evidence in support of decrease in the incidence of postoperative infectious [risk ratio (RR) (95% confidence interval [CI]): 0.64 (0.55, 0.74)] and length of hospital stay [mean difference (95% CI): -1.88 (-2.91, -0.84 days)] in those receiving IMN. Even though significant benefit was observed for noninfectious complications [RR (95% CI): 0.82 (0.71, 0.95)], the quality of evidence was low. There was no statistically significant benefit on mortality [RR (95% CI): 0.83 (0.49, 1.41)].Conclusions: IMN is beneficial in reducing postoperative infectious and noninfectious complications and shortening hospital stay in patients undergoing major open gastrointestinal surgery.
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- Mumithrakamatchi, Annadurai K., et al.
(författare)
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Melatonin imparts tolerance to combined drought and high-temperature stresses in tomato through osmotic adjustment and ABA accumulation
- 2024
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Ingår i: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, environmental stresses viz., drought and high-temperature negatively impacts the tomato growth, yield and quality. The effects of combined drought and high-temperature (HT) stresses during the flowering stage were investigated. The main objective was to assess the effects of foliar spray of melatonin under both individual and combined drought and HT stresses at the flowering stage. Drought stress was imposed by withholding irrigation, whereas HT stress was imposed by exposing the plants to an ambient temperature (AT)+5°C temperature. The drought+HT stress was imposed by exposing the plants to drought first, followed by exposure to AT+5°C temperature. The duration of individual and combined drought or HT stress was 10 days. The results showed that drought+HT stress had a significant negative effect compared with individual drought or HT stress alone. However, spraying 100 µM melatonin on the plants challenged with individual or combined drought and HT stress showed a significant increase in total chlorophyll content [drought: 16%, HT: 14%, and drought+HT: 11%], Fv/Fm [drought: 16%, HT: 15%, and drought+HT: 13%], relative water content [drought: 10%, HT: 2%, and drought+HT: 8%], and proline [drought: 26%, HT: 17%, and drought+HT: 14%] compared with their respective stress control. Additionally, melatonin positively influenced the stomatal and trichome characteristics compared with stress control plants. Also, the osmotic adjustment was found to be significantly increased in the melatonin-sprayed plants, which, in turn, resulted in an increased number of fruits, fruit set percentage, and fruit yield. Moreover, melatonin spray also enhanced the quality of fruits through increased lycopene content, carotenoid content, titratable acidity, and ascorbic acid content, compared with the stress control. Overall, this study highlights the usefulness of melatonin in effectively mitigating the negative effects of drought, HT, and drought+HT stress, thus leading to an increased drought and HT stress tolerance in tomato.
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