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Diabetic foot ulcers can lead to severe complications, including infection, gangrene, and even amputation, significantly impacting patients' quality of life. The application of anti-inflammatory compounds loaded into chitosan membranes offers targeted therapeutic effects, reducing inflammation and promoting tissue regeneration. This study evaluates the therapeutic efficacy of T7, a selective COX-2 inhibitor, incorporated into chitosan-polyvinylalcohol (CS-PVA) membranes for diabetic wound treatment. Cytotoxicity analysis showed high cell viability across various T7 concentrations, indicating minimal cytotoxicity. In silico pharmacology identified 98 potential inflammation-related targets for T7, further supported by GO and KEGG enrichment analyses. Developmental toxicity tests on zebrafish embryos indicated no significant toxicity up to 100 µM concentration. SEM and FTIR analyses confirmed the successful incorporation of T7 into the CS-PVA membrane, while XRD analysis indicated structural stability. The drug release assay demonstrated a sustained release profile, crucial for prolonged therapeutic efficacy. Antibacterial activity assays revealed significant inhibition of common pathogens. In vivo wound healing assays showed accelerated wound closure and enhanced collagen deposition, with histological and immunohistochemistry analyses supporting improved tissue architecture and reduced inflammation. Gene expression analysis confirmed reduced inflammatory markers. These findings suggest that T7-loaded CS-PVA membranes offer a promising, multifaceted approach to diabetic wound treatment, combining anti-inflammatory, antimicrobial, and collagen-promoting properties for effective wound healing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Non-steroidal anti-inflammatory drugs (NSAIDs) have been researched for their capacity to reduce cancer incidence, primarily due to their COX-2 inhibition properties. However, concerns have arisen regarding the precision of their targeting abilities. Nanoparticle approaches are revolutionizing cancer treatment by enabling targeted drug delivery, which enhances the efficacy and reduces the toxicity of chemotherapy. Particularly, chitosan-based nanoparticles are noteworthy for their biocompatibility, biodegradability, and ability to improve drug delivery. In this study, we synthesized folic acid-conjugated, 1,5-diaryl pyrazole-loaded chitosan (FA-CS-DP) nanoparticles using the ionic gelation method. The bioavailability and anti-neoplastic effects in a 7,12-dimethylbenzanthracene (DMBA)-exposed zebrafish model was investigated. MTT assay showed dose-dependent cytotoxicity of FA-CS-DP nanoparticles against MCF-7 breast cancer. The nanoparticles showed no toxicity to zebrafish embryos up to 100 μg/mL. The nanoparticle reduced oxidative stress and enhanced apoptosis in zebrafish exposed to DMBA. The morphological examination suggests that tumor growth was prevented in the zebrafish's surface and internal regions. The gene expression analysis confirmed the decrease in the expression of anti-inflammatory genes, such as cox-2 and nf-κb, and apoptosis inhibitor genes, such as bcl-2 and mdm2. By regulating the anti-inflammatory and apoptosis inhibitor genes, FA-CS-DP nanoparticle prevents neoplastic growth in the zebrafish model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis, a chronic autoimmune disorder characterized by joint inflammation, is thought to be exacerbated by bacterial infections, notably Proteus mirabilis. This study explores the combined effects of quercetin, a potent antioxidant and anti-inflammatory flavonoid, and chondroitin sulfate, known for its cartilage-protective properties, as a potential therapeutic approach. Molecular docking analyses revealed favourable interactions between these compounds and key pro-inflammatory cytokines IL-6 and TNF-α, suggesting their potential to disrupt inflammation-related signaling pathways. In vitro assays demonstrated that the quercetin-chondroitin sulfate combination (1:1 ratio) significantly inhibited oxidative stress and hemolysis, highlighting its enhanced anti-inflammatory and membrane-protective effects. The free radical scavenging assays further confirmed the antioxidant potential of this combination, which demonstrated strong radical scavenging activity. Antimicrobial assays showed notable antibacterial effects, with an increased inhibition zone against P. mirabilis when quercetin and chondroitin sulfate were combined, suggesting a synergistic antimicrobial action. In vivo, zebrafish subjected to bacterial stress showed improved survival rates with the quercetin and chondroitin sulfate combination treatment, along with enhanced mineralization and significant modulation of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities, indicating its protective role in maintaining joint health. Furthermore, gene expression analysis revealed a substantial reduction in pro-inflammatory markers, including TNF-α and IL-6, demonstrating the quercetin and chondroitin sulfate combination's ability to mitigate inflammation. Together, these findings suggest that the quercetin and chondroitin sulfate combination hold significant therapeutic potential in reducing oxidative stress, inflammation, and microbial-induced RA exacerbations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the aquatic environment, the primary pollutants of heavy metals and pharmaceuticals always occur in coexisting forms, and the research about combined impacts remains unclear, especially transgenerational effects. Cadmium (Cd) is a heavy metal that can damage the endocrine reproduction systems and cause thyroid dysfunction in fish. Meanwhile, ketoprofen (KPF) is a nonsteroidal anti-inflammatory drug (NSAID) that can cause neurobehavioral damage and physiological impairment. However, to our knowledge, the combined exposure of Cd and KPF in transgenerational studies has not been reported. In this investigation, sexually mature zebrafish were subjected to isolated exposure and combined exposure to Cd (10 μg/L) and KPF (10 and 100 μg/L) at environmentally relevant concentrations for 42 days. In this background, breeding capacity, chemical accumulation rate in gonads, and tissue morphologies are investigated in parental fish. This is followed by examining the malformation rate, inflammation rate, and gene transcription in the F1 offspring. Our results indicate that combined exposure of Cd and KPF to the parental fish could increase the chemical accumulation rate and tissue damage in the gonads of fish and significantly reduce the breeding ability. Furthermore, these negative impacts were transmitted to its produced F1 embryos, reflected by hatching rate, body deformities, and thyroid axis-related gene transcription. These findings provide further insights into the harm posed by Cd in the presence of KPF to the aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The prevalent use of Azorubine (E122) and the unintentional food additive, Bisphenol A (BPA), in ready-to-drink (RTD) beverages raises significant health concerns, especially for children. The combined impact on embryonic development must be explored despite individual safety assessments. Our investigation revealed that the combined exposure of E122 and BPA at beverage concentration significantly induces mortality and morphological deformities, including reduced growth, pericardial edema, and yolk sac edema. The co-exposure triggers oxidative stress, impairing antioxidant enzyme responses and resulting in lipid and cellular damage. Notably, apoptotic cells are observed in the neural tube and notochord of the co-exposed larvae. Critical genes related to the antioxidant response elements (nrf2, ho1, and nqo1), apoptosis activation (bcl2, bax, and p53), and pro/anti-inflammatory cytokines (nfkb, tnfa, il1b, tgfb, il10, and il12) displayed substantial changes, highlighting the molecular mechanisms. Behavior studies indicated hypo-locomotion with reduced thigmotaxis and touch response in co-exposed larvae, distinguishing it from individual exposures. These findings underscore the neurodevelopmental impacts of E122 and BPA at reported beverage concentrations, emphasizing the urgent need for comprehensive safety assessments, particularly for child consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The escalating focus on ageing-associated disease has generated substantial interest in the phenomenon of cognitive impairment linked to diabetes. Hyperglycemia exacerbates oxidative stress, contributes to β-amyloid accumulation, disrupts mitochondrial function, and impairs cognitive function. Existing therapies have certain limitations, and apigenin (AG), a natural plant flavonoid, has piqued interest due to its antioxidant, anti-inflammatory, and anti-hyperglycemic properties. So, we anticipate that AG might be a preventive medicine for hyperglycemia-associated amnesia. To test our hypothesis, naïve zebrafish were trained to acquire memory and pretreated with AG. Streptozotocin (STZ) was administered to mimic hyperglycemia-induced memory dysfunction. Spatial memory was assessed by T-maze and object recognition through visual stimuli. Acetylcholinesterase (AChE) activity, antioxidant enzyme status, and neuroinflammatory genes were measured, and histopathology was performed in the brain to elucidate the neuroprotective mechanism. AG exhibits a prophylactic effect and improves spatial learning and discriminative memory of STZ-induced amnesia in zebrafish under hyperglycemic conditions. AG also reduces blood glucose levels, brain oxidative stress, and AChE activity, enhancing cholinergic neurotransmission. AG prevented neuronal damage by regulating brain antioxidant response elements (ARE), collectively contributing to neuroprotective properties. AG demonstrates a promising effect in alleviating memory dysfunction and mitigating pathological changes via activation of the Nrf2/ARE mechanism. These findings underscore the therapeutic potential of AG in addressing memory dysfunction and neurodegenerative changes associated with hyperglycemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigates the individual and combined toxic effects of Bisphenol A (BPA) and Cadmium (Cd) in zebrafish, recognizing the complex mixture of pollutants organisms encounter in their natural environment. Examining developmental, neurobehavioral, reproductive, and physiological aspects, the study reveals significant adverse effects, particularly in combined exposures. Zebrafish embryos exposed to BPA + Cd exhibit synergistically increased mortality, delayed hatching, and morphological abnormalities, emphasizing the heightened toxicity of the combination. Prolonged exposure until 10 days post-fertilization underscores enduring effects on embryonic development. BPA and Cd induce oxidative stress, as evidenced by increased production of reactive oxygen species and lipid peroxidation. This oxidative stress disrupts cellular functions, affecting lipid metabolism and immune response. Adult zebrafish exposed to BPA and Cd for 40 days display compromised neurobehavioral functions, altered antioxidant defenses, and increased oxidative stress, suggesting potential neurotoxicity. Additionally, disruptions in ovarian follicle maturation and skeletal abnormalities indicate reproductive and skeletal impacts. Histological analysis reveals significant liver damage, emphasizing the synergistic hepatotoxicity of BPA and Cd. Molecular assessments further demonstrate compromised cellular defense mechanisms, synaptic function, and elevated cellular stress and inflammation-related gene expression in response to combined exposures. Bioaccumulation analysis highlights differential tissue accumulation patterns. In conclusion, this study provides comprehensive insights into the multifaceted toxicological effects of BPA and Cd in zebrafish, raising concerns about potential adverse impacts on environmental ecosystems and human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Polyethylene terephthalate (PET), a commonly used polymer in various food and plastic bag containers, has raised significant concerns regarding its environmental and human health risks. Despite its prevalent use, the impact of PET exposure on aquatic environments and its potential to induce neurotoxic conditions in species remain poorly understood. Furthermore, the mechanisms underlying amelioration through natural product intervention are not well-explored. In light of these gaps, our study aimed to elucidate the neurotoxic effects of PET in zebrafish through waterborne exposure, and to mitigate its neurological impact using luteolin-graphene oxide nanoparticles., Methods and Results: Our investigation revealed that exposure to PET in water triggered adverse effects in zebrafish larvae, particularly in the head region. We observed heightened oxidative stress, lipid peroxidation, and cell death, accompanied by impaired antioxidant defense enzymes. Furthermore, abnormal levels of acetylcholine esterase and nitric oxide in the zebrafish brain indicated cognitive impairment. To address these issues, we explored the potential neuroprotective effects of luteolin-graphene oxide nanoparticles. These nanoparticles demonstrated efficacy in localizing within the zebrafish brain, enhancing their therapeutic impact against PET exposure. Treatment with luteolin-graphene oxide nanoparticles not only mitigated PET-induced neurological alterations but also exhibited a neuroprotective effect. This was evidenced by the regulation of pro-inflammatory cytokine gene expression in the zebrafish brain. Additionally, normalization of locomotory behavior in PET-exposed zebrafish following nanoparticle treatment underscored the potential effectiveness of luteolin-graphene oxide nanoparticles as a treatment against PET-induced neurotoxicity., Conclusions: In summary, our study emphasizes the urgent need to investigate the environmental and health risks associated with PET. We demonstrate the potential of luteolin-graphene oxide nanoparticles as an effective intervention against PET-induced neurotoxicity in zebrafish., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Bacteria communicate with each other through contact-dependent and contact-independent mechanisms. While certain contact-dependent mechanisms, such as Type IV and Type VI, have received considerable attention, nanotubes-mediated communication among gut bacteria remains largely unknown. The purpose of this study is to demonstrate the presence of nanotube production in both gut commensal and gut pathogenic bacteria. And also aims to show how Enterococcus faecalis utilizes nanotubes to combat Salmonella ser. Typhi (S. Typhi), a pathogen in the gut. The research findings suggest that the formation of nanotubes is an inherent trait observed in both Gram-positive and Gram-negative bacteria. Interestingly, bacteria generate nanotubes in dynamic environments, biofilms, and even within the gut of zebrafish. These nanotubes develops over time in accordance with the duration of incubation. Furthermore, E. faecalis effectively combats S. Typhi through mechanisms that depend on physical contact rather than indirect methods. Notably, E. faecalis protects zebrafish larvae from S. Typhi infections by reducing reactive oxygen species and cell death, and concurrently boosting the production of antioxidant enzymes. It is hypothesized that E. faecalis might eliminate S. Typhi by transferring toxic metabolites into the pathogen via nanotubes. Gene expression analysis highlights that proinflammatory markers such as TNF-α, IL-1β, and IL-6 are elevated in Salmonella-infected larvae. However, co-treatment with E. faecalis counters this effect. Findings of this study underscores the significance of nanotubes as a vital machinery for bacterial communication and distribution of virulence factors. Exploring nanotubes-mediated communication at a molecular level could pave the way for innovative therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) leaches from plastic products have become a major inevitable concern among the research society. Human exposure to BPA leads to deleterious effects on multiple organs by the induced hyper inflammatory and oxidative stress responses. Due to the compromised antioxidant mechanism, the brain environment was highly susceptible and required special concern to ameliorate the effects of BPA. Hence, this study investigates the potential of neem-derived semi natural deacetyl epoxyazadiradione (DEA) against the oxidative stress and inflammatory response induced by BPA exposure in N9 cells and zebrafish larvae. The results from the in vitro analyses showed a decrease in cell viability in the MTT assay and a decline in mitochondrial damage in BPA-exposed N9 cells. Further in vivo, results revealed that pre-treatment of DEA to zebrafish larvae has significantly reduced the level of superoxide anion and increased the production of antioxidant enzymes such as SOD, CAT, GST, GPx and GR. We also found a significant decrease in the production of nitric oxide (p < 0.0001) and iNOS gene expression at 150 μM concentration. Further, DEA pre-treatment improved the behaviour of zebrafish larvae by ameliorating the production of the AChE enzyme. In conclusion, DEA protected zebrafish larvae from BPA toxicity by ameliorating oxidative stress and inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Exogenous toxicants cause oxidative stress and damage to brain cells, resulting in inflammation. Neuroinflammation is important in the pathobiology of various neurological illnesses, including Alzheimer's disease (AD). In this context, Bisphenol A (BPA), a common toxin, causes oxidative damage and has been linked to neurological problems. An O-methylated isoflavone known as Biochanin A (5,7-dihydroxy-4'-methoxy-isoflavone, BCA) is considered to be a phytoestrogen, which is abundant in some legume plants and soy which have preventive effects against cancer, osteoporosis, menopausal symptoms and oxidative stress. However, the mechanism by which BCA protected the prenatal neurological stress are not known. So that, in this study we investigated the BCA neuroprotective effect against BPA-induced neuroinflammation in zebrafish embryo models. For this study, fertilized zebrafish embryos are exposed to BPA (1 µM) with or without BCA. Our finding suggested that BCA co-exposure prevented the depletion of antioxidant defense enzymes by BPA and reduced the production of intracellular ROS production, superoxide anion (O 2 - ), lipid peroxidation (LPO), lactate dehydrogenase (LDH) and nitric oxide (NO) levels in the head that aided in safeguarding neuronal development. Baseline locomotion was rendered and a total distance was calculated to assess the motor function. Exposure to BCA increased acetylcholinestrase (AChE) and improved motor neuron functions. It also reduced the pro-inflammatory response expression and prevented neuroinflammation. Our study suggests that BCA has a positive role in the attenuation or amelioration of neuronal oxidative damage and locomotory behaviour induced by BPA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alcoholic liver disease is one of the most prominent liver diseases in the world. Lipid accumulation accompanied by oxidative stress and inflammation in the liver is the most important pathogenesis of ALD. This study was designed to investigate the anti-oxidative, fat metabolism-regulating, and anti-inflammatory potential of N2, a seminatural analog of Nimbin. The ethanol exposure was found to induce liver injury on zebrafish larvae, such as liver inflammation, lipid accumulation, oxidative stress, and hepatocytes apoptosis. N2 was subjected to ADMET screening in-silico, and it was observed N2's co-exposure decreased the ROS, apoptosis, lipid peroxidation, and macrophage accumulation in the liver of larval zebrafish. To further study the mechanism behind ethanol hepatotoxicity and the hepatoprotective behavior of N2, gene expression changes were determined in zebrafish. The results of this study revealed that ethanol exposure upregulated mRNA expressions of SREBP1, C/EBP-α, FAS and provoked more severe oxidative stress and hepatitis via upregulation of inflammatory cytokines TNF-α, IL-10, IL-1β, iNOS, COX-2. However, the N2 co-exposure protected the hepatocyte damage and almost reversed the condition by downregulating the mRNA levels. The study suggested that N2 could be an effective therapeutic agent for the treatment of ALD and other inflammatory conditions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polycystic ovarian syndrome (PCOS) causes swollen ovaries in women at reproductive age due to hormonal disorder with small cysts on the outer edges. The cause of the disorder is still yet to be found. Multiple factors have increased PCOS prevalence, hyperandrogenism, oxidative stress, inflammation, and insulin resistance. Various animal PCOS models have been developed to imitate the pathophysiology of PCOS in humans. Zebrafish is one of the most versatile animal experimental models because of the transparency of the embryos, small size, and rapid growth. The zebrafish similarity to higher vertebrates made it a useful non-mammalian model for PCOS drug testing and screening. This review provides an insight into the usage of zebrafish, a non-mammalian model for PCOS, as an opportunity for evaluating future initiatives in such a research domain., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Polycystic ovarian syndrome (PCOS) is a hormonal disorder that causes enlargement of ovaries and follicular maturation arrest, which lacks efficient treatment. N2, a semi‐natural triterpenoid from the neem family, was already reported to have antioxidant and antiinflammatory properties in our previous report. This study investigated the anti‐androgenic property of N2 on testosterone‐induced oxidative stress in Chinese Hamster Ovarian cells (CHO) and PCOS zebrafish model. The testosterone exposure disrupted the antioxidant enzymes and ROS level and enhanced the apoptosis in both CHO cells and PCOS zebrafish. However, N2 significantly protected the CHO cells from ROS and apoptosis. N2 improved the Gonado somatic index (GSI) and upregulated the expression of the SOD enzyme in zebrafish ovaries. Moreover, the testosterone‐induced follicular maturation arrest was normalized by N2 treatment in histopathology studies. In addition, the gene expression studies of Tox3 and Denndla in zebrafish demonstrated that N2 could impair PCOS condition. Furthermore, to confirm the N2 activity, the in‐silico studies were performed against PCOS susceptible genes Tox3 and Dennd1a using molecular docking and molecular dynamic simulations. The results suggested that N2 alleviated the oxidative stress and apoptosis in‐vitro and in‐vivo and altered the expression of PCOS key genes. [ABSTRACT FROM AUTHOR]

• Withaferin a inhibits growth of S. aureus though cell membrane damage. • Tube adherence test indicated biofilm inhibition by withaferin a at Sub-MIC concentration. • Treatment of withaferin a reduced inflammation in S. aureus infected zebrafish. • Protection from pathogen-induced cellular damage by withaferin a treatment was observed through histology analysis. The emergence of antibiotic resistance is the most challenging factor for developing a proper drug to treat S. aureus infection. These bacterial pathogens can survive in fresh water and spread to various environments. Plant sources, especially pure compounds, are the material of interest amongst researchers for developing drugs of therapeutic value. Here, we report the bacterial clearance and anti-inflammatory potential of the plant compound Withaferin A, using the zebrafish infection model. The minimum inhibitory concentration of the Withaferin A was calculated as 80 µM against S. aureus. The DAPI/PI staining and scanning electron microscopy analysis showed the pore-forming mechanism of Withaferin A on the bacterial membrane. Along with the antibacterial activity, the results from the tube adherence test reveal the antibiofilm property of Withaferin A. In vivo studies were demonstrated to determine the effect of Withaferin A on survival, inflammatory response and behavioural changes during S. aureus infection. Staining zebrafish larvae with neutral red and Sudan black indicates a substantial decrease in the number of localized macrophages and neutrophils. The gene expression analysis showed the downregulation of inflammatory marker genes. Additionally, we observed the improvement in locomotory behaviour among Withaferin A treatment adult zebrafish. In conclusion, S. aureus can infect zebrafish and induces toxicological effect. In comparison, the results from in vitro and in vivo experiments suggest that Withaferin A can be used for synergistic antibacterial, antibiofilm and anti-inflammatory activity to treat infections due S. aureus. [ABSTRACT FROM AUTHOR]