Issue Cover de Wit, Koos; Beuers, Ulrich; Mukha, Anna ...
Liver international,
03/2023, Volume:
43, Issue:
3
Journal Article
Peer reviewed
Open access
The cover image is based on the Original Article Rifaximin stimulates nitrogen detoxification by PXR‐independent mechanisms in human small intestinal organoids by Koos de Wit et al., ...https://doi.org/10.1111/liv.15491.
Acute‐on‐chronic liver failure (ACLF) is a frequent cause of death in cirrhosis. Albumin dialysis with the molecular adsorbent recirculating system (MARS) decreases retained substances and improves ...hemodynamics and hepatic encephalopathy (HE). However, its survival impact is unknown. In all, 189 patients with ACLF were randomized either to MARS (n = 95) or to standard therapy (SMT) (n = 94). Ten patients (five per group) were excluded due to protocol violations. In addition, 23 patients (MARS: 19; SMT: 4) were excluded from per‐protocol (PP) analysis (PP population n = 156). Up to 10 6‐8‐hour MARS sessions were scheduled. The main endpoint was 28‐day ITT and PP survival. There were no significant differences at inclusion, although the proportion of patients with Model for Endstage Liver Disease (MELD) score over 20 points and with spontaneous bacterial peritonitis (SBP) as a precipitating event was almost significantly greater in the MARS group. The 28‐day survival was similar in the two groups in the ITT and PP populations (60.7% versus 58.9%; 60% versus 59.2% respectively). After adjusting for confounders, a significant beneficial effect of MARS on survival was not observed (odds ratio OR: 0.87, 95% confidence interval CI 0.44‐1.72). MELD score and HE at admission and the increase in serum bilirubin at day 4 were independent predictors of death. At day 4, a greater decrease in serum creatinine (P = 0.02) and bilirubin (P = 0.001) and a more frequent improvement in HE (from grade II‐IV to grade 0‐I; 62.5% versus 38.2%; P = 0.07) was observed in the MARS group. Severe adverse events were similar. Conclusion: At scheduled doses, a beneficial effect on survival of MARS therapy in patients with ACLF could not be demonstrated. However, MARS has an acceptable safety profile, has significant dialysis effect, and nonsignificantly improves severe HE. (HEPATOLOGY 2013)
Aflatoxins are strong cancerogenic compounds predominantly produced by certain strains of the Aspergillus genus. Due to their extreme stability in different conditions, it is very difficult to remove ...them completely in human diet and animal feeds. In this way aflatoxins are triggering numerous healthy problems (such as liver cancer) and thus becoming a huge burden to the hygiene system and food industry worldwide.
Therefore, seeking for an effective technique to degrade aflatoxins to a threshold level has been a “hot-topic” among researchers. Traditional methods to detoxify aflatoxins include physical and chemical treatments, such as an extrusion cooking process and ammoniation, respectively. Meanwhile a bio-degradation by microorganisms gains its popularity due to its friendliness to both environment and body health. Natural phytochemicals (plant extracts) which have great capability to remove aflatoxins without causing any damage on human and animals come out as an improvement.
However, a fully and systematically discussion of the methods of detoxification for aflatoxins is still not available. Therefore, in the present review we briefly enumerate several traditional strategies, update newly methods, particularly the potential use of natural phytochemicals, and discuss some mechanisms during the detoxification period, summarizing merits and demerits of these methods. We suggest that this important information and our humble opinions could help researchers to understand the degradation of methods for aflatoxins.
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•Aflatoxin B1 is classified as a Group I carcinogen by IARC.•Aflatoxin contamination is a great threat to human and animal health.•Physical, chemical and biological degradations are three major ways.•Phytochemicals have also been regarded as a promising approach.
Microbial symbionts of herbivorous insects have been suggested to aid in the detoxification of plant defense compounds; however, quantitative studies on microbial contribution to plant toxin ...degradation remain scarce. Here, we demonstrate microbiome‐mediated degradation of plant‐derived toxic isothiocyanates in the cabbage stem flea beetle Psylliodes chrysocephala, a major pest of oilseed rape. Suppression of microbiota in antibiotic‐fed beetles resulted in up to 11.3‐fold higher levels of unmetabolized isothiocyanates compared to control beetles but did not affect other known detoxification pathways in P. chrysocephala. We characterized the microbiome of laboratory‐reared and field‐collected insects using 16S rRNA amplicon sequencing and isolated bacteria belonging to the three core genera Pantoea, Acinetobacter and Pseudomonas. Only Pantoea isolates rapidly degraded isothiocyanates in vitro, and restored isothiocyanate degradation in vivo when reintroduced in antibiotic‐fed beetles. Pantoea was consistently present across beetle life stages and in field and lab populations. In addition, Pantoea was detected in undamaged tissues of the host plant Brassica rapa, indicating that P. chrysocephala could possibly acquire an isothiocyanate detoxifying bacterium through their diet. Our results demonstrate that both insect endogenous mechanisms and the microbiota can contribute to the detoxification of plant defense compounds and together they can better account for the fate of ingested plant metabolites.
Selection of chemical-resistant predatory mites is a good alternative to balance the contradiction between chemical control and biological control. Previously, a resistant strain of Neoseiulus ...barkeri for chlorpyrifos was obtained. In the current study, two up-regulated (NbCYP3A6, NbCYP3A16) and one down-regulated (NbCYP3A24) P450s were screened through differential expression analysis and other detoxification-related genes such as CCEs, GST, etc. were not found. 3D modelling and molecular docking indicated that the chlorine at position 5 on the pyridine ring of chlorpyrifos, as well as a methyl group, were closest to the heme iron of the enzymes (less than 5 Å). Three active recombinant P450 proteins were heterologously expressed and metabolized with chlorpyrifos in vitro. HPLC assay showed that only NbCYP3A24 could metabolize chlorpyrifos, with a metabolism rate of 21.60 %. Analysis of the m/z of metabolites by LC-MS/MS showed that chlorine at the 5C position of chlorpyrifos was stripped and hydroxylated, whereas chlorpyrifos-oxon, a common product of oxidation by P450, was not found. Knockdown of the NbCYP3A24 gene in the susceptiblestrain did reduce the susceptibility of N. barkeri to chlorpyrifos, suggesting that the biological activity of the metabolite may be similar to chlorpyrifos-oxon, thus enhancing the inhibitory effect on the target.
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•Three highly active P450 proteins of N. barkeri were successfully heterologously expressed.•The active region of the three P450s, heme iron, is distant from the P = O bond of chlorpyrifos.•Chlorpyrifos was dechlorinated and hydroxylated following the action of the down-regulated P450 protein.•Knockdown of NbCYP3A24 improved chlorpyrifos-tolerance in N. barkeri.
Natural enemies of arthropods contribute considerably to agriculture by suppressing pests, particularly when combined with chemical control. Studies show that insect recovery after insecticide ...application is rare. Here, we discovered the recovery of the predatory bug Arma chinensis from knockdown following the application of β-cypermethrin but not five other insecticides. A. chinensis individuals were more tolerant to β-cypermethrin than lepidopteran and coleopteran larvae, which did not recover from knockdown. We assessed A. chinensis recovery by monitoring their respiration and tracking locomotion through the entire process. We identified and verified the trans-regulation of detoxifying genes, including those encoding cytochrome P450s and α/β-hydrolase, which confer recovery from β-cypermethrin exposure in A. chinensis, by mitogen-activated protein kinase (MAPK) and cAMP response element binding protein (CREB). Furthermore, we discovered a novel mechanism, the neurotransmitter clearance, in vivo during the recovery process, by which the insect initiated the removal of excessive dopamine with a degrading enzyme ebony. Overall, these results provide mechanistic insights into the detoxification and neurotransmitter clearance that jointly drive insect recovery from insecticide exposure.
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•Arma chinensis recovered from applications of β-cypermethrin, a rare phenomenon among insects exposed to pesticides.•Metabolic detoxification by trans-regulated detoxifying genes in the A. chinensis entire recovery process was verified.•Arma chinensis rebalanced the excitatory neurotransmission by increasing ebony expression to remove the excessive dopamine.•Arma chinensis has the potential to develop resistance to cypermethrin, that is expected to be compatible with insecticides.
Lignocellulosic biomass (LCB) is expected to play a significant role in achieving the goal of biomass-to-bioenergy conversion due to its wide distribution and low price. Acidogenic dark fermentation ...of LCB is a promising approach to the sustainable production of biohydrogen (bioH2) from this valuable substrate. Because of its inherent recalcitrance, LCB requires pretreatment to increase its digestibility and enable its improved utilization. Intense thermochemical pretreatments solubilize the lignin and hemicellulose and lead to the formation of a variety of inhibitory byproducts, such as short-chain carboxylic acids, furfural, 5-hydroxymethylfurfural (5-HMF), vanillin, and syringaldehyde, which interfere with the physiological and metabolic functions of dark fermentative microbiota, thus inhibiting bioH2 production. To offset the negative impacts of these inhibitors on bioH2 production, approaches to detoxify lignocellulosic hydrolysates have been considered. This review comprehensively discusses the generation of lignocellulosic inhibitory byproducts in commonly used, contemporary pretreatment regimens and their inhibitory effects on dark fermentative H2 production. Furthermore, the mechanisms of inhibiting H2 producing bacteria and their effects on bacterial community dynamics in mixed cultures are reviewed. State-of-the-art strategies for detoxifying pretreated LCB are discussed. The selection of desirable alternative lignocellulose pretreatment strategies that produce less or no inhibitory byproducts are highlighted. Finally, this review discusses the economic aspects of bioH2 production from LCB, considering the pretreatment and detoxification process. Given the limitations of previous studies, future research for developing cost-effective strategies to overcome byproduct inhibition during dark fermentation of pretreated LCB are suggested.
•The effects of lignocellulosic inhibitors on bioH2 production are discussed.•The mechanisms of action of inhibitors on bioH2-producing bacteria are elucidated.•The changes in H2-producing microbiota structure due to inhibitors are interpreted.•State-of-the-art strategies to mitigate problems caused by inhibition are reviewed.•In situ detoxification allows the removal of inhibitors during dark fermentation.
Development of a biotechnological system for rapid degradation of pesticides is important to mitigate the environmental, food security, and health risks that they pose. Degradation of atrazine (ATZ) ...and isoproturon (IPU) in rice crops promoted by the brassinosteroid (BR) signaling component BRASSINAZOLE RESISTANT4 (OsBZR4) is explored. OsBZR4 is localized in the plasma membrane and nucleus, and is strongly induced by ATZ and IPU exposure. Transgenic rice OsBZR4-overexpression (OE) significantly enhances resistance to ATZ and IPU toxicity, improving growth, and reducing ATZ and IPU accumulation (particularly in grains) in rice crops. Genetic destruction of OsBZR4 (CRISPR/Cas9) increases rice sensitivity and leads to increased accumulation of ATZ and IPU. OE plants promote phase I, II, and III metabolic reactions, and expression of corresponding pesticide degradation genes under ATZ and IPU stress. UPLC-Q-TOF-MS/MS analysis reveals increased relative contents of ATZ and IPU metabolites and conjugates in OE plants, suggesting an increased OsBZR4 expression and consequent detoxification of ATZ and IPU in rice and the environment. The role of OsBZR4 in pesticide degradation is revealed, and its potential application in enhancing plant resistance to pesticides, and facilitating the breakdown of pesticides in rice and the environment, is discussed.
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•OsBZR4 positively regulates rice growth and detoxification with ATZ and IPU stress.•OsBZR4 expression decreases ATZ and IPU residues in rice and its environment.•Overexpression of OsBZR4 facilitates the expression of pesticide degradation genes.•Overexpression of OsBZR4 promotes metabolic reactions in rice.•OsBZR4-overexpression plants may reduce ATZ and IPU contamination in rice.
Aflatoxins are a class of carcinogenic mycotoxins produced by Aspergillus fungi and are known to contaminate a large portion of the world's food supply. Aflatoxin B1 (AFB1) is the most potent of ...these compounds and has been well-characterized to lead to the development of hepatocellular carcinoma (HCC) in humans and animals. This review focuses on the metabolism of AFB1, including epoxidation and DNA adduction, as it concerns the initiation of cancer and the underlying mechanisms. The link between AFB1 consumption and HCC is also discussed including synergistic interactions with the hepatitis B virus. Toxic effects of AFB1, including growth suppression, malnutrition, and immunomodulation, are also covered. This review also describes recent reports of AFB1 occurrence in global food supplies and exposures in occupational settings. Furthermore, a summary of recent detoxification methods is included to indicate the present state of the field in developing aflatoxin control methods. This information shows that AFB1 occurs frequently in food supplies at high concentrations, particularly in maize. Regarding detoxification methods, chemical control methods were the fastest methods that still retained high detoxification efficacy. The information presented here highlights the need to implement new and/or existing detoxification methods to reduce the global burden of AFB1 toxicity.
•AFB1 is a potent hepatocarcinogen that contaminates a large portion of the world’s food supply.•After ingestion, AFB1 forms DNA adducts which initiates carcinogenesis and can work synergistically with hepatitis B virus.•AFB1 is also strongly linked with many other toxicities including growth impairment, malnutrition, and immunomodulation.•Diverse chemical and biological control methods have been studied to reduce AFB1 levels in food.
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•Heavy metal detoxification pathways of microorganisms have been summarized.•Heavy metal remediation mechanisms of microorganisms have been included.•Interactions between remediation ...mechanisms and detoxification pathways were discussed.•The next-generation of bioremediation technologies has been put forward.
Heavy metal pollution, because of its high toxicity, non-biodegradability and biological enrichment, has seriously threatened the health of human beings and the stability of ecological system. The immobilization, removal and detoxification of active heavy metal ions in natural environment can be achieved through microbial activities. Because of its outstanding advantages including high efficiency, low cost and environment friendly, the development of high-efficiency biological techniques to clean up toxic metal wastes have already drawn scientists’ great attention. After millions of years of evolution, some microorganisms are resistant to heavy metal ions and able to remediate heavy metal pollution. However, the relationship of microbial resistance system and their remediation ability towards heavy metal ions is still unclear. To uncover the underneath, we summarized heavy metal bioremediation technologies as well as their detoxification pathways in this review, which will contribute to find their interconnections and develop more efficient bioremediation technologies. Additionally, the future potential of gene-editing associated and advanced material associated multi-functional bioremediation technologies have been put forward in this review.
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