Advances in metal-organic framework-based nanozymes in ROS scavenging medicine.

Reactive oxygen species (ROS) play important roles in regulating various physiological functions in the human body, however, excessive ROS can cause serious damage to the human body, considering the various limitations of natural enzymes as scavengers of ROS in the body, the development of better materials for the scavenging of ROS is of great significance to the biomedical field, and nanozymes, as a kind of nanomaterials which can show the activity of natural enzymes. Have a good potential for the development in the area of ROS scavenging. Metal-organic frameworks (MOFs), which are porous crystalline materials with a periodic network structure composed of metal nodes and organic ligands, have been developed with a variety of active nanozymes including catalase-like, superoxide dismutase-like, and glutathione peroxidase-like enzymes due to the adjustability of active sites, structural diversity, excellent biocompatibility, and they have shown a wide range of applications and prospects. In the present review, we first introduce three representative natural enzymes for ROS scavenging in the human body, methods for the detection of relevant enzyme-like activities and mechanisms of enzyme-like clearance are discussed, meanwhile, we systematically summarize the progress of the research on MOF-based nanozymes, including the design strategy, mechanism of action, and medical application, etc. Finally, the current challenges of MOF-based nanozymes are summarized, and the future development direction is anticipated. We hope that this review can contribute to the research of MOF-based nanozymes in the medical field related to the scavenging of ROS.

Corrigendum: Gut microbes reveal Pseudomonas medicates ingestion preference via protein utilization and cellular homeostasis under feed domestication in freshwater drum, Aplodinotus grunniens.

[This corrects the article DOI: 10.3389/fmicb.2022.861705.].

PPAR Signaling Maintains Metabolic Homeostasis under Hypothermia in Freshwater Drum (Aplodinotus grunniens).

Aplodinotus grunniens, known as freshwater drum, is a kind of eurythermal freshwater fish that is widely distributed in North America. In 2019, our research group reached a milestone on its artificial breeding and cultivation and have investigated its physiological adaption to the environment, providing a breakthrough and prospects for aquaculture. However, its adaptability and metabolic homeostasis to hypothermia is not fully understood. In this experiment, cold stress was conducted at 18 °C (LT18) and 10 °C (LT10) with 25 °C as control (Con) for 8 days to explore the effects of short-term hypothermia on the physiology and metabolism of freshwater drum. From the results, the level of free essential amino acids in LT18 and LT10 decreased significantly after 2 days cold stress compared with Con. Furthermore, plasma total triglyceride (TG) content and lipase (LPS) activity were decreased at LT10 for 2d. With RNA-seq in the liver, metabolic-related signaling, especially amino acid synthesis and lipid metabolism, was inhibited by hypothermia. Specifically, the PPAR signaling pathway is correlated with the inhibition of lipid and amino acid metabolism induced by hypothermia. These data confirmed that PPAR signaling maintains lipid and amino acid metabolic homeostasis during cold stress. These results give a theoretical foundation for hypothermia resistance in the area of metabolic homeostasis for freshwater drum.

Hypothermia-Mediated Apoptosis and Inflammation Contribute to Antioxidant and Immune Adaption in Freshwater Drum, Aplodinotus grunniens.

Hypothermia-exposure-induced oxidative stress dysregulates cell fate and perturbs cellular homeostasis and function, thereby disturbing fish health. To evaluate the impact of hypothermia on the freshwater drum (Aplodinotus grunniens), an 8-day experiment was conducted at 25 °C (control group, Con), 18 °C (LT18), and 10 °C (LT10) for 0 h, 8 h, 1 d, 2 d, and 8 d. Antioxidant and non-specific immune parameters reveal hypothermia induced oxidative stress and immunosuppression. Liver ultrastructure alterations indicate hypothermia induced mitochondrial enlargement, nucleoli aggregation, and lipid droplet accumulation under hypothermia exposure. With the analysis of the transcriptome, differentially expressed genes (DEGs) induced by hypothermia were mainly involved in metabolism, immunity and inflammation, programmed cell death, and disease. Furthermore, the inflammatory response and apoptosis were evoked by hypothermia exposure in different immune organs. Interactively, apoptosis and inflammation in immune organs were correlated with antioxidation and immunity suppression induced by hypothermia exposure. In conclusion, these results suggest hypothermia-induced inflammation and apoptosis, which might be the adaptive mechanism of antioxidation and immunity in the freshwater drum. These findings contribute to helping us better understand how freshwater drum adjust to hypothermia stress.

Transcriptome Analysis of Hepatopancreas Provides Insights into Differential Metabolic Mechanisms of Eriocheir sinensis Feeding on Trash Fish and Formulated Feed.

BACKGROUND: The Chinese mitten crab, Eriocheir sinensis (E. sinensis), is a popular crab species in both domestic and foreign markets. Trash fish are essential for E. sinensis breeding, but have caused serious water pollution. The municipal party committee for the main production areas of E. sinensis implemented a ban on feeding on trash fish since 2020. METHODS: In this study, we performed a culture experiment of E. sinensis feeding on trash fish and formulated feed, with comparative transcriptome analysis on hepatopancreas of E. sinensis. RESULTS: The results indicate that formulated feed causes no significant difference in growth, survival rate or content of amino acids in the muscles of adult E. sinensis. Formulated feed caused a slight downregulation of pathways involved in amino acid metabolism, development, energy metabolism and homeostasis maintenance. CONCLUSIONS: On the whole, formulated feed can serve as an undifferentiated substitution for trash fish. This study provides a theoretical foundation for optimizing research on E. sinensis feed.

miR-1/AMPK-Mediated Glucose and Lipid Metabolism under Chronic Hypothermia in the Liver of Freshwater Drum, Aplodinotus grunniens.

Our previous study demonstrated that low temperature could induce hepatic inflammation and suppress the immune and oxidation resistance of freshwater drum. However, the metabolism, especially the glucose and lipid metabolism involved, is poorly studied. To further explore the chronic hypothermia response of freshwater drum, an 8-day hypothermia experiment was conducted at 10 °C to investigate the effect of chronic hypothermia on glucose and lipid metabolism via biochemical and physiological indexes, and metabolic enzyme activities, miRNAs and mRNA-miRNA integrate analysis in the liver. Plasma and hepatic biochemical parameters reveal chronic hypothermia-promoted energy expenditure. Metabolic enzyme levels uncover that glycolysis was enhanced but lipid metabolism was suppressed. Differentially expressed miRNAs induced by hypothermia were mainly involved in glucose and lipid metabolism, programmed cell death, disease, and cancerization. Specifically, KEGG enrichment indicates that AMPK signaling was dysregulated. mRNA-miRNA integrated analysis manifests miR-1 and AMPK, which were actively co-related in the regulatory network. Furthermore, transcriptional expression of key genes demonstrates hypothermia-activated AMPK signaling by miR-1 and subsequently inhibited the downstream glucogenic and glycogenic gene expression and gene expression of fatty acid synthesis. However, glycogenesis was alleviated to the control level while fatty acid synthesis was still suppressed at 8 d. Meanwhile, the gene expressions of glycolysis and fatty acid oxidation were augmented under hypothermia. In conclusion, these results suggest that miR-1/AMPK is an important target for chronic hypothermia control. It provides a theoretical basis for hypothermia resistance on freshwater drum.

Gut Microbes Reveal Pseudomonas Medicates Ingestion Preference via Protein Utilization and Cellular Homeostasis Under Feed Domestication in Freshwater Drum, Aplodinotus grunniens.

With strong demand for aquatic products, as well as a rapid decrease in global fishery resources and capture fisheries, domesticating animals to provide more high-quality proteins is meaningful for humans. Freshwater drum (Aplodinotus grunniens) is widely distributed in the wild habitats of North America. However, the research on A. grunniens and the feed domestication with diets composed of artificial compounds remains unclear. In this study, a 4-month feeding domestication experiment was conducted with A. grunniens larvae to evaluate the underlying mechanism and molecular targets responsible for alternations in the ingestion performance. The results indicated that a significant increase in the final body weight was exhibited by the feed domesticated group (DOM, 114.8 g) when compared to the group that did not ingest the feed (WT, 5.3 g) as the latest version we raised From the result, the final body weight exhibited significant increase between unfavorable with the feed (WT, 5.3 g) and feed domesticated group (DOM, 114.8 g). In addition, the enzyme activity of digestive enzymes like amylase, lipase, and trypsin was increased in DOM. Genes related to appetite and perception, such as NPY4R, PYY, and LEPR, were activated in DOM. 16s rRNA gene sequencing analysis revealed that Pseudomonas sp. increased from 58.74% to 89.77% in DOM, which accounts for the dominant upregulated microbial community at the genus level, followed by Plesiomonas. Analogously, Mycobacterium, Methylocystis, and Romboutsia also accounted for the down-regulated microbes in the diversity. Transcriptome and RT-PCR analysis revealed that feed domestication significantly improved protein digestion and absorption, inhibited apoptosis by AGE-RAGE signaling, and activated extracellular matrix remodeling by relaxin signaling. Integrated analysis of the microbiome and host transcriptome revealed that Pseudomonas-mediated ingestion capacity, protein utilization, and cellular homeostasis might be the underlying mechanism under feed domestication. These results indicate Pseudomonas and its key genes relating to food ingestion and digestion could serve as the molecular targets for feed domestication and sustainable development in A. grunniens.

Integrated transcriptome and phosphoproteome analyses reveal that fads2 is critical for maintaining body LC-PUFA homeostasis.

Fatty acid desaturate 2 (Fads2) is associated with many chronic diseases. Nevertheless, comprehensive researches on its role have not been performed. We here conducted an integrated analysis of long-chain polyunsaturated fatty acid (LC-PUFA) metabolism of fads2-deletion zebrafish (fads2-/-) by transcriptomics, proteomics and phosphoproteomics. Compared with wild type zebrafish (WT), fads2-/- showed significantly higher contents of hepatic linoleic acid (all-cis-9,12-C18:2), α-linolenic acid (all-cis-9,12,15-C18:3) and docosapetaenoic acid (all-cis-7,10,13,16,19-C22:5), and lower contents of γ-linolenic acid (all-cis-6,9,12-C18:3), stearidonic acid (all-cis-6,9,12,15-C18:4) and docosahexaenoic acid (all-cis-4,7,10,13,16,19-C22:6), accompanied by an increased n-6/n-3 PUFA level. In total, we identified 1608 differentially expressed genes (DEGs), 209 differentially expressed proteins (DEPs) and 153 differentially expressed phosphorylated proteins (DEPPs) with 190 sites between fads2-/- and WT. Transcriptome and proteome analysis simultaneously aggregated these DEGs and DEPs into LC-PUFA synthesis and PPAR signaling pathways. Further interaction network analysis of the DEPPs showed that spliceosome and protein processing in endoplasmic reticulum pathway were critical groups. Additionally, we determined seven highly phosphorylated kinases and a highly expressed phosphatase in fads2-/- zebrafish. These results give insights into the mechanism by which fads2 affects metabolic disease occurrence, and provide datasets for target selections for human disease treatment. SIGNIFICANCE: Balanced LC-PUFA composition was deeply associated with body health, while changes of LC-PUFAs usually induced serious diseases such as cardiovascular disease, type 2 diabetes and inflammatory disease. Fatty acid desaturase 2 (Fads2), subordinating to the fatty acid desaturase protein family, catalyzes the first desaturation reaction in LC-PUFA synthesis. Although Fads2 is associated with many chronic diseases including metabolic abnormalities, type 2 diabetes and obesity, comprehensive researches on its role have not been performed. On the basis of the integrated transcriptome, proteome and phosphoproteome analysis, we identified that fads2 was critical for maintaining body LC-PUFA homeostasis. Moreover, the crucial pathways including PPAR signaling pathway, spliceosome and protein processing in endoplasmic reticulum pathway, and candidate kinase targets associated with LC-PUFA metabolism were determined. These findings will contribute to the revealing of the mechanism and supply possible datasets for target selection for human disease treatment.