Ferulic acid alleviates avermectin induced renal injury in carp by inhibiting inflammation, oxidative stress and apoptosis.

Avamectin (AVM), a macrolide antibiotic, is widely used in fisheries, agriculture, and animal husbandry, however, its irrational use poses a great danger to aquatic organisms. Ferulic acid (FA) is a natural chemical found in the cell walls of plants. It absorbs free radicals from the surrounding environment and acts as an antioxidant. However, the protective effect of FA against kidney injury caused by AVM has not been demonstrated. In this study, 60 carp were divided into the control group, AVM group (2.404 µg/L), FA+AVM group and FA group (400 mg/kg). Pathological examination, quantitative real-time PCR (qPCR), reactive oxygen species (ROS) and western blot were used to evaluate the preventive effect of FA on renal tissue injury after AVM exposure. Histological findings indicated that FA significantly reduced the swelling and infiltration of inflammatory cells in the kidney tissues of carp triggered by AVM. Dihydroethidium (DHE) fluorescent probe assay showed that FA inhibited the accumulation of kidney ROS. Biochemical results showed that FA significantly increased glutathione (GSH) content, total antioxidant capacity (T-AOC) and catalase (CAT) activity, and decreased intracellular malondialdehyde (MDA) content. In addition, western blot results revealed that the protein expression levels of Nrf2 and p-NF-κBp65 in the carp kidney were inhibited by AVM, but reversed by the FA. The qPCR results exhibited that FA significantly increased the mRNA levels of tgf-ß1 and il-10, while significantly down-regulated the gene expression levels of tnf-α, il-6 and il-1ß. These data suggest that FA can reduce oxidative stress and renal tissue inflammation induced by AVM. At the same time, FA inhibited the apoptosis of renal cells induced by AVM by decreasing the transcription level and protein expression level of Bax, and increasing the transcription level and protein expression level of Bcl2, PI3K and AKT. This study provides preliminary evidence for the theory that FA reduces the level of oxidative stress, inflammation response and kidney tissue damage caused by apoptosis in carp, providing a theoretical basis for the prevention and treatment of the AVM.

Abamectin induced brain and liver toxicity in carp: The healing potential of silybin and potential molecular mechanisms.

Abamectin (ABM) abuse contaminated aquatic environment and posed a potential threat to fish health as well as public safety. Silybin (SIL), a flavonoid, has been widely used as a novel feed additive to promote fish health. This research was to explore the potential antagonistic mechanism between ABM and SIL on brain and liver toxicity was investigated in common carp. Sixty carp were divided into four groups at random: the Control group, the SIL group, the ABM group, and ABM + SIL group. This experiment lasted for 30 d. According to behavioral observation, the detection of levels of acetylcholinesterase (AchE), iron, and mRNA expression levels of blood-brain barrier (BBB) related tight junction proteins (ZO-1, Claudin7, Occludin, MMP2, MMP9, and MMP13) in brain tissues, it was found that SIL relieved neurobehavioral disorders caused by ABM-induced BBB destruction in carp. H&E staining showed SIL mitigated nerve injury and liver injury caused by ABM. Oil Red O staining and liver-related parameters showed that SIL alleviated hepatotoxicity and lipid metabolism disorder caused by ABM exposure. Furthermore, this work also explored the specific molecular mechanism of SIL in liver protection and neuroprotection. It was shown that SIL lowered ROS levels in liver and brain tissues via the GSK-3ß/TSC2/TOR pathway. Simultaneously, SIL inhibited NF-κB signaling pathway and played an anti-inflammatory role. In conclusion, we believed that SIL supplementation has a protective effect on the brain and liver by regulating oxidative stress and inflammation.

Quercetin attenuates avermectin-induced cardiac injury in carp through inflammation, oxidative stress, apoptosis and autophagy.

As an important antibiotic, avermectin (AVM) has been widely used in China, but its unreasonable application has caused serious harm to the water environment. In view of the various pharmacological effects of quercetin (QUE), such as anti-inflammatory and antioxidant, the scientific hypothesis that "QUE may cause carp poisoning by inhibiting AVM" was proposed in this study. However, its protective effect in AVM -induced heart damage has not been reported. QUE reduced the symptoms of AVM toxicity and decreased the levels of creatine kinase, lactate dehydrogenase, and creatine kinase in the serum of carp. By histological observation, QUE was found to significantly reduce cardiac fiber swelling in carp. A DHE fluorescence probe study showed that QUE was able to inhibit AVM -induced accumulation of reactive oxygen species (ROS) in carp myocardium. We found that QUE significantly increased the intracellular antioxidant enzymes CAT, T-AOC and GSH enzyme activity and reduced intracellular MDA content. In addition, QUE significantly increased il-10 and tgf-ß1 expression, and significantly down-regulated tnf-α, il-6, il-1ß and inos expression. Tunel assay showed that QUE attenuated AVM -induced apoptosis, significantly decreased the transcript levels of pro-apoptosis-related genes, and increased the expression of anti-apoptosis-related genes. We also detected the protein expression of LC3 in the AVM group and QUE + AVM group, and found that the expression of LC3 was significantly increased in both groups compared with the Control group, but after adding QUE, the expression of LC3 was significantly decreased compared with the AVM group. In addition, the transcript levels of p62 and atg5 were also detected by qPCR. QUE significantly increased the expression of p62 and decreased the expression of atg5, suggesting that QUE could attenuate AVM -induced cardiac autophagy in carp. This study will provide preliminary evidence of the principle of QUE attenuating AVM -induced myocardial injury in carp from four aspects, including oxidative stress, inflammatory response, apoptosis and autophagy, and provide a theoretical basis for its prevention and treatment.

Ferulic acid attenuates difenoconazole exposure induced liver injury in carp by modulating oxidative damage, inflammation and apoptosis.

Difenoconazole (DFZ) is a widely used triazole fungicide in agricultural production. However, the presence of DFZ residue in the environment poses a significant risk to non-target organisms. Ferulic acid (FA) is a phenolic compound known for its antioxidant and anti-inflammatory properties. This study aims to investigate the hepatic damage caused by DFZ in carp and explore the mechanism through which FA alleviates this damage. The findings revealed that FA enhanced the antioxidant capability of the carp's liver and reduced the accumulation of reactive oxygen species (ROS) in the liver tissue. Moreover, FA regulated the transcriptional levels of inflammation-related factors, effectively preventing the inflammatory response triggered by the NF-κB signaling pathway. Additionally, TUNEL results demonstrated that DFZ initiated apoptosis, while dietary supplementation with FA decreased the protein expression levels of Bax and Cytochrome C (Cyt c) and the transcriptional levels of bax, caspase3, caspase9, p53 genes. Furthermore, FA increased the protein expression and transcriptional levels of Bcl-2. In conclusion, FA protects against liver injury induced by DFZ exposure in carp by modulating oxidative damage, inflammation, and apoptosis.

Dietary additive ferulic acid alleviated oxidative stress, inflammation, and apoptosis induced by chronic exposure to avermectin in the liver of common carp (Cyprinus carpio).

Avermectin (AVM) has been utilized extensively in agricultural production since it is a low-toxicity pesticide. However, the pollution caused by its residues to fisheries aquaculture has been neglected. As an abundant polyphenolic substance in plants, ferulic acid (FA) possesses anti-inflammatory and antioxidant effects. The goal of the study is to assess the FA's ability to reduce liver damage in carp brought on by AVM exposure. Four groups of carp were created at random: the control group; the AVM group; the FA group; and the FA + AVM group. On day 30, and the liver tissues of carp were collected and examined for the detection of four items of blood lipid as well as the activity of the antioxidant enzymes catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in carp liver tissues by biochemical kits, and the transcript levels of indicators of oxidative stress, inflammation and apoptosis by qPCR. The results showed that liver injury, inflammation, oxidative stress, and apoptosis were attenuated in the FA + AVM group compared to the AVM group. In summary, dietary addition of FA could ameliorate the hepatotoxicity caused by AVM in carp by alleviating oxidative stress, inflammation, apoptosis in liver tissues.

Mussel-inspired polymer with catechol and cationic Lys functionalities for dentin wet bonding.

Mussels can form tough and long-lasting adhesions to organic and inorganic surfaces in saline and impactive severe aquatic environments. Similar to mussel adhesion, dentin bonding occurs in a wet environment. However, unlike mussels, it is difficult to achieve long-lasting bonds with dentin. Moreover, water is considered a major hindrance in dentin bonding. Inspired by the synergistic effect of cationic lysine (Lys) and catechol on the elimination of the hydration layer during mussel adhesion, a catechol- and Lys-functionalized polymerizable polymer (catechol-Lys-methacrylate [CLM]) was synthesized to replicate the complex synergy between amino acids and catechol. The bond-promoting potential of 5 â€‹mg/mL CLM primer was confirmed using an in vitro wet dentin-bonding model, which was characterized by an improvement in bond strength and durability. CLM can adhere to wet demineralized dentin, with Lys acting as a molecular vanguard to expel water. Subsequently, a myriad of interfacial interactions can be obtained by introducing the catechol group into the interface. Additionally, tough and long-lasting adhesion, similar to that formed by mussels, can be achieved by grafting CLM onto type I collagen via covalent bonds, hydrogen bonds, Van der Waals interactions, and cation-π interactions, which can enhance the mechanical and chemical stability of collagen, increase the enzymatic resistance of collagen, and provide additional physical/chemical adhesion to dentin bonds. Catechol- and cationic Lys-functionalized polymers can improve the stability of the resin-dentin interface under wet conditions.

Enhancing bioactivity and stability of polymer-based material-tissue interface through coupling multiscale interfacial interactions with atomic-thin TiO2 nanosheets.

Stable and bioactive material-tissue interface (MTF) basically determines the clinical applications of biomaterials in wound healing, sustained drug release, and tissue engineering. Although many inorganic nanomaterials have been widely explored to enhance the stability and bioactivity of polymer-based biomaterials, most are still restricted by their stability and biocompatibility. Here we demonstrate the enhanced bioactivity and stability of polymer-matrix bio-composite through coupling multiscale material-tissue interfacial interactions with atomically thin TiO2 nanosheets. Resin modified with TiO2 nanosheets displays improved mechanical properties, hydrophilicity, and stability. Also, we confirm that this resin can effectively stimulate the adhesion, proliferation, and differentiation into osteogenic and odontogenic lineages of human dental pulp stem cells using in vitro cell-resin interface model. TiO2 nanosheets can also enhance the interaction between demineralized dentinal collagen and resin. Our results suggest an approach to effectively up-regulate the stability and bioactivity of MTFs by designing biocompatible materials at the sub-nanoscale. Electronic Supplementary Material: Supplementary material (further details of fabrication and characterization of TiO2 NSs and TiO2-ARCs, the bioactivity evaluation of TiO2-ARCs on hDPSCs, and the measurement of interaction with demineralized dentin collagen) is available in the online version of this article at 10.1007/s12274-022-5153-1.

Photothermal-enhanced antibacterial and antioxidant hydrogel dressings based on catechol-modified chitosan-derived carbonized polymer dots for effective treatment of wound infections.

Bacterial infection and excessive reactive oxygen species (ROS) remain challenging factors contributing to the delayed healing of chronic wounds. Although various antibacterial and antioxidant hydrogel dressings have been developed to accelerate wound healing, multifunctional hydrogels fabricated by rationally designing and introducing carbonized polymer dots (CPDs) have rarely been reported. Herein, inspired by the mussel biomimetic approach, we synthesized 3,4-dihydroxybenzaldehyde functionalized chitosan (DFC), and then the polymeric precursor was pyrolyzed into CPDs with abundant amino and catechol groups on the surface, which endowed it with a highly positively charged surface that could activate the photothermal effect under near-infrared (NIR) light irradiation. Finally, the nanocomposite hydrogel (PVA@CPDs) was simply constructed by directly mixing polyvinyl alcohol (PVA) with CPDs, utilizing the freeze-thaw cycle method to form a gel, in which, CPDs as a center of polyfunctional nanoparticles drove the formation of PVA microcrystalline crosslinking and endowed the PVA substrate with versatile functionalities. Remarkable and comprehensive improvements in the swelling behavior, mechanical properties and adhesive strength of the hydrogel could be conveniently achieved with the suitable loading of CPDs. The in vitro experiments demonstrated that the PVA@CPDs hydrogel presented broad-spectrum and rapid bactericidal activity, concurrently acting as an effective antioxidant being able to scavenge free radicals. In addition, no obvious cytotoxicity was observed for the multifunctional hydrogel after incubation with L02 cells. In vivo evaluation in an infected full-thickness skin wound model demonstrated that the PVA@CPDs hydrogel promoted wound closure without any side effects. As a consequence, the current work manifests a facile yet versatile strategy to develop effective and biocompatible multifunctional hydrogel dressings for bacteria-infected wound healing.

A mussel glue-inspired monomer-etchant cocktail for improving dentine bonding.

OBJECTIVES: The humid oral environment adversely affects the interaction between a functionalised primer and dentine collagen after acid-etching. Robust adhesion of marine mussels to their wet substrates instigates the quest for a strategy that improves the longevity of resin-dentine bonds. In the present study, an etching strategy based on the incorporation of biomimetic dopamine methacrylamide (DMA) as a functionalised primer into phosphoric acid etchant was developed. The mechanism and effect of this DMA-containing acid-etching strategy on bond durability were examined. METHODS: Etchants with different concentrations of DMA (1, 3 or 5 mM) were formulated and tested for their demineralisation efficacy. The interaction between DMA and dentine collagen, the effect of DMA on collagen stability and the collagenase inhibition capacity of the DMA-containing etchants were evaluated. The effectiveness of this new etching strategy on resin-dentine bond durability was investigated. RESULTS: All etchants were capable of demineralising dentine and exposing the collagen matrix. The latter strongly integrated with DMA via covalent bond, hydrogen bond and Van der Waals' forces. These interactions significantly improve collagen stability and inhibited collagenase activity. Application of the etchant containing 5 mM DMA achieved the most durable bonding interface. CONCLUSION: Dopamine methacrylamide interacts with dentine collagen in a humid environment and improves collagen stability. The monomer effectively inactivates collagenase activity. Acid-etching with 5 mM DMA-containing phosphoric acid has the potential to prolong the longevity of bonded dental restorations without compromising clinical operation time. CLINICAL SIGNIFICANCE: The use of 5 mM dopamine methacrylamide-containing phosphoric acid for etching dentine does not require an additional clinical step and has potential to improve the adhesive performance of bonded dental restorations.