Sub-chronically exposing zebrafish to environmental levels of methomyl induces dysbiosis and dysfunction of the gut microbiota.

The widespread use of carbamate pesticides has led to numerous environmental and health concerns, including water contamination and perturbation of endocrine homeostasis among organisms. However, there remains a paucity of research elucidating the specific effects of methomyl on gut microbial composition and physiological functions. This study aimed to investigate the intricate relationship between changes in zebrafish bacterial communities and intestinal function after 56 days of sub-chronic methomyl exposure at environmentally relevant concentrations (0, 0.05, 0.10, and 0.20 mg/L). Our findings reveal significant methomyl-induced morphological changes in zebrafish intestines, characterized by villi shortening and breakage. Notably, methomyl exposure down-regulated nutrient and energy metabolism, and drug metabolism at 0.05-0.10 mg/L, while up-regulating cortisol, inflammation-related genes, and apoptotic markers at 0.20 mg/L. These manifestations indicate physiological stress imposition and disruption of gut microbiota equilibrium, impacting metabolic processes and instigating low-grade inflammatory responses and apoptotic cascades. Importantly, changes in intestinal function significantly correlated with shifts in specific bacterial taxa abundance, including Shewanella, Rubrobacter, Acinetobacter, Bacillus, Luteolibacter, Nocardia, Defluviimonas, and Bacteroides genus. In summary, our study underscores the potential adverse effects of environmental methomyl exposure on aquatic organisms, emphasizing the necessity for further research to mitigate its repercussions on environmental health and ecosystem stability.

Preparation and characterization of BSA-loaded liraglutide and platelet fragment nanoparticle delivery system for the treatment of diabetic atherosclerosis.

BACKGROUND: Diabetic atherosclerosis is one of the main causes of morbidity and mortality worldwide, but its therapeutic options are limited. Liraglutide (LIR), a synthetic analog of GLP-1 approved as an anti-obesity drug by the FDA, has been reported as a promising drug for diabetic atherosclerosis. However, the main problem with LIR is its use that requires regular parenteral injections, which necessitates the improvement of drug delivery for increased efficiency and minimization of injection numbers. RESULTS: The objective of our present study was to prepare and characterize nanoparticles (BSA@LIR-PMF) for targeted drug delivery using LIR-encapsulated platelet membrane fragments (PMF) coated bovine serum albumin (BSA). We used various methods to characterize the prepared nanoparticles and evaluated their efficiency on diabetes-induced atherosclerosis in vitro and in vivo. The results showed that the nanoparticles were spherical and had good stability and uniform size with intact membrane protein structure. The loading and encapsulation rates (LR and ER) of BSA@LIR-PMF were respectively 7.96% and 85.56%, while the cumulative release rate was around 77.06% after 24 h. Besides, we also examined the impact of BSA@LIR-PMF on the proliferation, migration, phagocytosis, reactive oxygen species (ROS) levels, oxidative phosphorylation, glycolysis, lactate and ATP levels, and lipid deposition in the aortas. The results indicated that BSA@LIR-PMF could effectively inhibit ox-LDL-stimulated abnormal cell proliferation and migration, reduce the level of ROS and lactate concentration, and enhance the level of ATP, thereby improving oxidative phosphorylation in ox-LDL-treated cells. CONCLUSION: BSA@LIR-PMF significantly inhibited diabetes-induced atherosclerosis. It was anticipated that the BSA@LIR-PMF nanoparticles might be used for treating diabetes-associated cardiovascular complications.

M2 macrophage-polarized anti-inflammatory microneedle patch for accelerating biofilm-infected diabetic wound healing via modulating the insulin pathway.

Macrophages play a pivotal role in the healing of diabetic ulcers. The sustained elevation of glucose levels damages the insulin signaling pathway in macrophages, leading to dysfunctional macrophages that struggle to transition from pro-inflammatory (M1) to reparative (M2) states. Therefore, modulating macrophage inflammatory responses via the insulin pathway holds promise for diabetic ulcer treatment. Additionally, the presence of biofilm impedes drug penetration, and the resulting immunosuppressive microenvironment exacerbates the persistent infiltration of pro-inflammatory M1 macrophages. Therefore, we designed an array of dissolvable microneedle (denoted as NPF@MN) loaded with self-assembled nanoparticles that could deliver NPF nanoparticles, acid-sensitive NPF-releasing Protocatechualdehyde (PA) with hypoglycemic and insulin-like effects, regulating macrophage polarization to an anti-inflammatory M2 phenotype. Additionally, this study extensively examined the mechanism by which NPF@MN accelerates the healing of diabetic ulcers through the activation of the insulin signaling pathway. Through RNA-seq and GSEA analysis, we identified a reduction in the expression of pathway-related factors such as IR, IRS-1, IRS-2, and SHC. Our work presents an innovative therapeutic approach targeting the insulin pathway in diabetic ulcers and underscores its translational potential for clinical management.

Microglia-neuron interactions promote chronic itch via the NLRP3-IL-1ß-GRPR axis.

BACKGROUND: Spinal astrocytes contribute to chronic itch via sensitization of itch-specific neurons expressing gastrin-releasing peptide receptor (GRPR). However, whether microglia-neuron interactions contribute to itch remains unclear. In this study, we aimed to explore how microglia interact with GRPR+ neurons and promote chronic itch. METHODS: RNA sequencing, quantitative real-time PCR, western blot, immunohistochemistry, RNAscope ISH, pharmacologic and genetic approaches were performed to examine the roles of spinal NLRP3 (The NOD-like receptor family, pyrin-containing domain 3) inflammasome activation and IL-1ß-IL1R1 signaling in chronic itch. Grpr-eGFP and Grpr KO mice were used to investigate microglia-GRPR+ neuron interactions. RESULTS: We observed NLRP3 inflammasome activation and IL-1ß production in spinal microglia under chronic itch conditions. Blockade of microglial activation and the NLRP3/caspase-1/IL-1ß axis attenuated chronic itch and neuronal activation. Type 1 IL-1 receptor (IL-1R1) was expressed in GRPR+ neurons, which are essential for the development of chronic itch. Our studies also find that IL-1ß+ microglia are localized in close proximity to GRPR+ neurons. Consistently, intrathecal injection of IL1R1 antagonist or exogenous IL-1ß indicate that the IL-1ß-IL-1R1 signaling pathway enhanced the activation of GRPR+ neurons. Furthermore, our results demonstrate that the microglial NLRP3/caspase-1/IL-1ß axis contributes to several different chronic itches triggered by small molecules and protein allergens from the environment and drugs. CONCLUSION: Our findings reveal a previously unknown mechanism in which microglia enhances the activation of GRPR+ neurons through the NLRP3/caspase-1/IL-1ß/IL1R1 axis. These results will provide new insights into the pathophysiology of pruritus and novel therapeutic strategies for patients with chronic itch.

Responses of bacterial and three sub-microeukaryote communities in the water of white shrimp Penaeus vannamei aquaculture ponds in two polyculture models.

Polyculture operations in freshwater aquaculture ponds can disrupt microbial communities. High-throughput sequencing was used to assess the impact of polyculture operations on bacterial and three sub-microeukaryote communities (fungi, zooplankton, and eukaryotic phytoplankton) in Penaeus vannamei aquaculture ponds containing oriental river prawns and giant freshwater prawns, respectively. The results showed that the bacterial community was less sensitive than the microeukaryote communities to both the polyculture activity and environmental variations. The polyculture of giant freshwater prawns rather than oriental river prawns was the primary factor affecting the beta diversity of the three sub-microeukaryote communities. This may be due to the larger biomass of the polyculture varieties of giant freshwater prawns compared with oriental river prawns. The polyculture activity of giant freshwater prawns with a higher density and that of oriental river prawns with a lower density increased the stochasticity of the community assembly of the three sub-microeukaryote communities. It also affected the topological properties of the microbial communities, including greater correlations between ecosystem elements, and reducing the correlations among zooplanktons. The eukaryotic phytoplankton was the only microbial community that could also be explained by nutrient variation (mainly the total nitrogen). This highlights the potential role of the eukaryotic phytoplankton as a suitable indicator of the effects of nutrient input into ecosystems.

Histone methyltransferase enzyme enhancer of zeste homolog 2 counteracts ischemic brain injury via H3K27me3-mediated regulation of PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Epigenetic histone methylation plays a crucial role in cerebral ischemic injury, particularly in the context of ischemic stroke. However, the complete understanding of regulators involved in histone methylation, such as Enhancer of Zeste Homolog 2 (EZH2), along with their functional effects and underlying mechanisms, remains incomplete. METHODS: Here, we employed a rat model of MCAO (Middle cerebral artery occlusion) and an OGD (Oxygen-Glucose Deprivation) model of primary cortical neurons to study the role of EZH2 and H3K27me3 in cerebral ischemia-reperfusion injury. The infarct volume was measured through TTC staining, while cell apoptosis was detected using TUNEL staining. The mRNA expression levels were quantified through quantitative real-time polymerase chain reaction (qPCR), whereas protein expressions were evaluated via western blotting and immunofluorescence experiments. RESULTS: The expression levels of EZH2 and H3K27me3 were upregulated in OGD; these expression levels were further enhanced by GSK-J4 but reduced by EPZ-6438 and AKT inhibitor (LY294002) under OGD conditions. Similar trends were observed for mTOR, AKT, and PI3K while contrasting results were noted for UTX and JMJD3. The phosphorylation levels of mTOR, AKT, and PI3K were activated by OGD, further stimulated by GSK-J4, but inhibited by EPZ-6438 and AKT inhibitor. Inhibition of EZH2 or AKT effectively counteracted OGD-/MCAO-induced cell apoptosis. Additionally, inhibition of EZH2 or AKT mitigated MCAO-induced infarct size and neurological deficit in vivo. CONCLUSIONS: Collectively, our results demonstrate that EZH2 inhibition exerts a protective effect against ischemic brain injury by modulating the H3K27me3/PI3K/AKT/mTOR signaling pathway. The results provide novel insights into potential therapeutic mechanisms for stroke treatment.

Effect of Chronic Exposure to Methomyl on Tissue Damage and Apoptosis in Testis of Tilapia (Oreochromis niloticus) and Recovery Pattern.

Tilapia were exposed to 0, 0.2, 2, 20, 200 µg/L methomyl for 30 days, and then transferred to methomyl-free water for 18 days. Caspase-8 in serum, apoptosis rate, microstructure and ultra-microstructure of testis were checked after methomyl exposure and at 18 days after transferring to methomyl-free water. There were no significant changes in Caspase-8 activity, apoptosis rate, and tissue structure in testis exposed to 0.2 and 2 µg/L compared with control. However, when tilapia exposed to 20 and 200 µg/L, the Caspase-8 activity and apoptosis rate were induced significantly, and tissue damage happened compared with the control. Thus it would appear 2 µg/L methomyl might be considered as the no observed adverse effect level. Recovery data showed that the effects produced by lower concentration of 20 µg/L were reversible but not at the higher 200 µg/L concentration.

Gut microbiota analysis of juvenile genetically improved farmed tilapia (Oreochromis niloticus) by dietary supplementation of different resveratrol concentrations.

The genetically improved farmed tilapia (GIFT, Oreochromis niloticus) is cultured widely for production of freshwater fish in China, while streptococcosis, likely related to pathogenic infections, occurs frequently in juvenile, mother, and operated GIFT. The gut microbiota plays an important role in nutrient digestibility in animals, and resveratrol (RES) has been used in feed for different freshwater fish species. Therefore, understanding changes in the tilapia gut microbiota across different concentrations of dietary RES supplementation is extremely important. The gut microbiota population in tilapia at 45 d after supplementation with different concentrations (0, 0.025, 0.05, 0.1 g/kg) of dietary RES was assessed by 16S rDNA gene sequencing. A total of 5445 operational taxonomic units were identified from all samples, and 14 phyla and 81 families were identified from all fecal samples. The bacteria of the phylum Firmicutes were significantly enriched in the 0.025 g/kg RES group when compared with the controls. Proteobacteria, Firmicutes and Cyanobacteria were the most dominant three phyla in all samples. With the increasing concentrations, the proportion of beneficial microbial taxa (Acetobacteraceae and Methylobacteriaceae) increased, whereas the proportion of harmful microbial taxa decreased, eg. Streptococcaceae except for 0.1 g/kg RES groups. RES did not affect the richness and diversity in tilapia gut microbiota. These findings provide information on the diversity and differences in GIFT gut microbiota database, and may contribute to developing strategies for management of diseases and long-term sustainability of O. niloticus culture.

Methanogenic community compositions in surface sediment of freshwater aquaculture ponds and the influencing factors.

Aquaculture ponds represent ecologically relevant environments to study the community composition and diversity of methanogenic assemblages, as well as their interactions with cultivated species and chemical indicators. In this study, aquaculture ponds with crab (Eriocheir sinensis), oriental river prawn (Macrobrachium nipponense), perch (Micropterus salmonides) and Wuchang fish (Parabramis pekinensis) were sampled, and Illumina high-throughput sequencing was used to investigate the methanogenic communities. The results revealed that the abundant methanogenic orders in surface sediment were Methanomicrobiales, Methanosarcinales and Methanocellales. The relative abundance of Methanocellales was higher in crab and prawn ponds as compared to other ponds. Methanogenic 16S rRNA gene abundance and beta diversity of the community was affected by the cultivated species. Methanogenic communities in aquaculture ponds with higher contents of total nitrogen and organic matter had decreased species richness, while those with higher contents of ammonia and nitrite had an overall decreased abundance of methanogens and their respective diversities. Overall, in addition to the differences in cultivated species, the consequent differences in farming practices including the types and amounts of feeds used, the contents of total nitrogen, organic matter, ammonia and nitrite could all influence the methanogenic community in surface sediment of aquaculture ponds.

Hepatic transcriptome analysis of juvenile GIFT tilapia (Oreochromis niloticus), fed diets supplemented with different concentrations of resveratrol.

The GIFT (Genetically Improved Farmed Tilapia) tilapia, Oreochromis niloticus, is cultured widely for the production of freshwater fish in China. Streptococcosis, which is related to pathogenic infections, occurs frequently in juvenile and adult female GIFT individuals. Resveratrol (RES) has been used in feed to control these infections in freshwater tilapia. To address the effects of RES on tilapia, we used high-throughput RNA sequencing technology (RNA-Seq, HiSeq. 2500) to explore the global transcriptomic response and specific involvement of hepatic mRNA of juvenile O. niloticus fed with diets containing different concentrations of (0, 0.025, 0.05, and 0.1g/kg) RES. A total of > 24,513,018 clean reads were generated and then assembled into 23,244 unigenes. The unigenes were annotated by comparing them against non-redundant protein sequence (Nr), non-redundant nucleotide (Nt), Swiss-Prot, Pfam, Gene Ontology database (GO), Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and 12,578 unigenes were annotated to the GO database. A total of 1444 (0.025g/kg RES), 1526 (0.05g/kg RES), and 3135 (0.1g/kg RES) genes were detected as significant differentially expressed genes (DEGs), when compared with the controls. A total of 6 (0.025 vs 0.05g/kg RES), 19 (0.025 vs 0.1g/kg RES), and 124 (0.05 vs 0.1g/kg RES) genes were detected as significant DEGs. Six genes, including dnah7x1, sox4, fam46a, hsp90a, ddit4, and nmrk2, were associated with an immune response. These findings provide information on the innate immunity of GIFT and might contribute to the development of strategies for the effective management of diseases and long-term sustainability of O. niloticus culture.

Archaeal community compositions in tilapia pond systems and their influencing factors.

Archaea, like the bacterial communities are gradually being realized as key players in the biogeochemical progress of water ecosystems. In this study, tilapia aquaculture ponds were used for an in-depth understanding of archaeal community compositions in water and surface sediment. Some of the main functions, as well as the communities' response patterns, to time variations, pond differences and some physio-chemical parameters were investigated. The results revealed the dominant phylum in both the water and surface sediment, as Euryarchaeota, while, the most abundant classes were: Halobacteria and Methanomicrobia respectively. Significant differences in the archaeal community compositions in the water and surface sediment, were observed in the early stages of cultivation, which became minimal at the later stage of the GIFT tilapia cultivation. Additionally to the differences in the most abundant classes, more OTUs were observed in water samples than in surface sediment samples. The methane generation could be attributed to the large proportion of methanogens found in both pond water and in the surface sediment. Furthermore, the archaeal community compositions in water and the surface sediment were shaped mainly by temporal variations and pond differences respectively. In the pond water, the archaeal community compositions were highly co-related to the concentration changes of ammonia, sulfate and total nitrogen; while in the surface sediment, the correlation to the content changes was significant in total phosphorus. The archaeal community compositions in surface sediment should be considered as an indicator for future environmental capacity studies in aquaculture.

Dietary supplementation with rutin has pro-/anti-inflammatory effects in the liver of juvenile GIFT tilapia, Oreochromis niloticus.

Dietary supplementation with rutin may have some pharmacological qualities including anti-inflammatory effects. Kupffer cell activation resulted in increased transcription of pro- and anti-inflammatory cytokines. The main purpose of this study was to investigate the pro- and anti-inflammatory activities in juvenile freshwater tilapia, Oreochromis niloticus, in response to 0.1 or 0.3 g/kg dietary supplementation of rutin. Results showed that hepatic IgM, anti-inflammatory-cytokines, and pro-inflammatory cytokines were significantly decreased in groups treated with high doses of rutin. Hepatic IgM and anti-inflammatory cytokines (IL-10 and IFN-γ) transcripts were significantly decreased, whereas the transcripts of the pro-inflammatory cytokines, TNFα and IL-1ß were significantly decreased, whereas IL-8 was significantly increased. The number of Kupffer cells in rutin-treated groups was significantly decreased, and scanning electron micrographs showed that rutin enriched the number of gut microvilli and secretion pits. With the phenomena of cell apoptosis occurred in the rutin groups, the present study demonstrated that optimum levels of rutin may be beneficial but excessive level may cause liver impairment, which may be absorbed by the gut and then transported to the liver.

Dietary risk ranking for residual antibiotics in cultured aquatic products around Tai Lake, China.

Antibiotics are widely used in aquaculture and therefore may be present as a dietary risk in cultured aquatic products. Using the Tai Lake Basin as a study area, we assessed the presence of 15 antibiotics in 5 widely cultured aquatic species using a newly developed dietary risk ranking approach. By assigning scores to each factor involved in the ranking matrices, the scores of dietary risks per antibiotic and per aquatic species were calculated. The results indicated that fluoroquinolone antibiotics posed the highest dietary risk in all aquatic species. Then, the total scores per aquatic species were summed by all 15 antibiotic scores of antibiotics, it was found that Crab (Eriocheir sinensis) had the highest dietary risks. Finally, the most concerned antibiotic category and aquatic species were selected. This study highlighted the importance of dietary risk ranking in the production and consumption of cultured aquatic products around Tai Lake.

Effect of methomyl on sex steroid hormone and vitellogenin levels in serum of male tilapia (Oreochromis niloticus) and recovery pattern.

Tilapia were exposed to sub-lethal concentrations of 0, 0.2, 2, 20 or 200 µg/L for 30 days, then transferred to methomyl-free water for 18 days. E2 , T, 11-KTand VTG in serum were examined. There were no significant changes in all the parameters in serum of tilapia exposed to 0.2 µg/L and 2 µg/L methomyl compared to the control. However, 20 µg/L and 200 µg/L have the potential to disrupt the endocrine system of male tilapia, as shown by its ability to increase VTG and E2 and decrease T and 11-KT in serum. Thus it would appear the no observed adverse effect level for sexual steroid hormones of methomyl is lower than 2 µg/L. Recovery data showed that the effects produced by 20µg/L were reversible but not at 200µg/L. Furthermore, the sensitivity of above parameters to methomyl followed the order of VTG>E2 >11-KT>T>GSI, suggesting VTG being the better biomarkers.

Characterizing bacterial communities in tilapia pond surface sediment and their responses to pond differences and temporal variations.

Bacterial community compositions in the surface sediment of tilapia ponds and their responses to pond characteristics or seasonal variations were investigated. For that, three ponds with different stocking densities were selected to collect the samples. And the method of Illumina high-throughput sequencing was used to amplify the bacterial 16S rRNA genes. A total of 662, 876 valid reads and 5649 operational taxonomic units were obtained. Further analysis showed that the dominant phyla in all three ponds were Proteobacteria, Bacteroidetes, Chloroflexi, and Acidobacteria. The phyla Planctomycetes, Firmicutes, Chlorobi, and Spirochaetae were also relatively abundant. Among the eight phyla, the abundances of only Proteobacteria, Bacteroidetes, Firmicutes, and Spirochaetae were affected by seasonal variations, while seven of these (with the exception of Acidobacteria) were affected by pond differences. A comprehensive analysis of the richness and diversity of the bacterial 16S rRNA gene, and of the similarity in bacterial community composition in sediment also showed that the communities in tilapia pond sediment were shaped more by pond differences than by seasonal variations. Linear discriminant analysis further indicated that the influences of pond characteristics on sediment bacterial communities might be related to feed coefficients and stocking densities of genetically improved farmed tilapia (GIFT).

Responses of glutathione-related antioxidant defense system in serum of Nile tilapia (Oreochromis niloticus) exposed to sublethal concentration of methomyl and recovery pattern.

Tilapia were exposed to sublethal concentrations of 0, 0.2, 2, 20, or 200 µg/L for 30 days, and then transferred to methomyl-free water for 18 days. GST, GPx, GR, GSH, and GSSG in tilapia serum were examined at 0, 6, 12, 18, 24, and 30 days after methomyl exposure and at 18 days after transferring to methomyl-free water. There were no significant changes in antioxidants activities and contents in serum of tilapia exposed to 0.2 µg/L. Significant increases in GST, GR, GPx, and GSSG accompanied by a decrease in GSH were observed following methomyl exposure to 2, 20, or 200 µg/L, suggesting the presence of oxidative stress. Thus, it would appear the 0.2 µg/L methomyl might be considered the no observed adverse effect level. Recovery data showed that the effects produced by lower concentration of 20 µg/L were reversible but not at the higher 200 µg/L concentration.

MicroRNA-198 inhibits proliferation and induces apoptosis of lung cancer cells via targeting FGFR1.

Lung cancer is the most common cause of death from cancer worldwide and recent studies have revealed that microRNAs play critical roles to regulate lung carcinogenesis. Here we present evidence to show the role of miR-198 in lung cancer development. Our results showed that ectopic expression of miR-198 inhibits the viability and induces the apoptosis of human non-small cell lung cancer cells A549 and NCI-H460, while miR-198 inhibition resulted in opposite changes. In nude mice miR-198 inhibits A549 growth of tumor graft. We further demonstrated that miR-198 directly targets fibroblast growth factor receptor 1 (FGFR1) in lung cancer cells. Restoring FGFR1 expression blocked the inhibitory function of miR-198, while FGFR1 inhibition achieved the similar phenotypes of miR-198 overexpression. Hence, our data delineates the molecular pathway by which miR-198 inhibits lung cancer cellular proliferation and induces apoptosis, and may have important implication for the treatment of lung carcinogenesis.

HMGCR is necessary for the tumorigenecity of esophageal squamous cell carcinoma and is regulated by Myc.

Hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme of mevalonate pathway, has been involved in the tumorigenesis of several tumor types. Our previous study has showed that statin, the inhibitor of HMGCR, inhibited the tumorigenecity of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. However, the function of HMGCR in the carcinogenesis of ESCC cells remains unknown. In this study, we have observed the up-regulation of HMGCR in ESCC tissues compared with the paired normal tissues. Over-expression of HMGCR in ESCC cells promoted cell growth and migration, while knockdown of the expression of HMGCR inhibited the growth, migration and colony formation of ESCC cells in vitro and in vivo. Furthermore, we found that oncogene Myc positively regulated the expression of HMGCR. Taken together, our study revealed the pivotal function of HMGCR and mevalonate pathway in the progression of ESCC and supported the clinical application of statin.

KGRT peptide incorporated hydrogel with antibacterial activity for wound healing by optimizing cellular functions via ERK/eNOS signaling.

Bacterial infected wounds, which is characterized by easy infection, multiple inflammation and slow healing, is a complex symptom, resulting from metabolic disorder of the wound microenvironment. In this study, a series of self-healing double-network hydrogels based on KGRT peptide (Lys-Gly-Arg-Thr) with antibacterial, anti-inflammatory and optimizing cellular functions were designed to promote the healing of infected wounds with full-thickness skin defects. Moreover, the dextran hydrogelintroduces a large number of side chains, which are entangled with each other in the Schiff base network to form an interpenetrating structure. The hydrogel might regulate cell metabolism, differentiation and vascular endothelial growth factor (VEGF) function. Importantly, both in vitro and in vivo data showed that hydrogel not only has good antibacterial properties (99.8 %), but also can eradicate bacterial biofilm, effectively reduce inflammation (down-regulated IL-1ß, TNF-α and ROS) and accelerate chronic wound healing process by speeding-up wound closure, increasing granulation tissue thickness, collagen deposition, angiogenesis (up-regulated CD31). The hydrogel could up-regulate mRNA expression of PI3K, AKT, ERK, eNOS, HIF-1α and VEGF, which were correlated with wound healing. Consistently, the hydrogel could promote infected wounds healing and inhibit inflammation through ERK/eNOS signaling pathway. Collectively, hydrogel has excellent clinical application potential for promoting infected wound healing.

Simultaneous antioxidant and neuroprotective effects of two-dimensional (2D) MXene-loaded isoquercetin for ischemic stroke treatment.

Oxidative stress and reactive oxygen species drive ischemic stroke and its related complications. New antioxidant medications are therefore crucial for treating ischemic stroke. We developed Ti2C@BSA-ISO nanocomposites loaded with the hydrophobic drug isoquercetin (ISO) encapsulated in BSA on Ti2C nano-enzymes as a novel therapeutic nanomedicine for the treatment of ischemic stroke targeting reactive oxygen species (ROS). TEM visually proved the successful preparation of Ti2C@BSA-ISO, and the FTIR, XPS, zeta potential and DLS together demonstrated the acquisition of Ti2C@BSA-ISO. In addition, the enzyme-mimicking activity of Ti2C was evaluated and the antioxidant capacity of Ti2C@BSA-ISO was verified. Ti2C@BSA-ISO was able to reverse the decrease in cellular activity caused by ROS. Experiments in vivo showed that Ti2C@BSA-ISO could promote neuroprotection and scavenging of ROS in the hippocampal CA1 area and cerebral cortex of rats, thereby inhibiting cellular death and alleviating ischaemic stroke. Specifically, Ti2C@BSA-ISO alleviated ischemic stroke by inhibiting NLRP3/caspase-1/GSDMD pathway-mediated pyroptosis. Our study demonstrates the effectiveness of nanomedicines that can be directly used as drugs for the treatment of ischemic stroke in synergy with other drugs, which greatly expands the application of nanomaterials in the treatment of ischemic stroke.