Indole-3 acetic acid induced cardiac hypertrophy in Wistar albino rats.

Indole-3-acetic acid (IAA) is the most widely utilized plant growth regulator. Despite its extensive usage, IAA is often overlooked as an environmental pollutant. Due to its protein-binding nature, it also functions as a uremic toxin, contributing to its association with chronic kidney disease (CKD). While in vitro and epidemiological research have demonstrated this association, the precise impact of IAA on cardiovascular disease in animal models is unknown. The main objective of this study is to conduct a mechanistic analysis of the cardiotoxic effects caused by IAA using male Wistar albino rats as the experimental model. Three different concentrations of IAA (125, 250, 500 mg/kg) were administered for 28 days. The circulating IAA concentration mimicked previously observed levels in CKD patients. The administration of IAA led to a notable augmentation in heart size and heart-to-body weight ratio, indicating cardiac hypertrophy. Echocardiographic assessments supported these observations, revealing myocardial thickening. Biochemical and gene expression analyses further corroborated the cardiotoxic effects of IAA. Dyslipidemia, increased serum c-Troponin-I levels, decreased SOD and CAT levels, and elevated lipid peroxidation in cardiac tissue were identified. Moreover, increased expression of cardiac inflammatory biomarkers, including ANP, BNP, ß-MHC, Col-III, TNF-α, and NF-κB, was also found in the IAA-treated animals. Histopathological analysis confirmed the cardiotoxic nature of IAA, providing additional evidence of its adverse effects on cardiovascular health. These results offer insights into the potential negative impact of IAA on cardiovascular function, and elucidating the underlying mechanisms of its cardiotoxicity.

Histone acetyltransferases derived RW20 protects and promotes rapid clearance of Pseudomonas aeruginosa in zebrafish larvae.

Pseudomonas is a group of bacteria that can cause a wide range of infections, particularly in people with weakened immune systems, such as those with cystic fibrosis or who are hospitalized. It can also cause infections in the skin and soft tissue, including cellulitis, abscesses and wound infections. Antimicrobial peptides (AMPS) are the alternative strategy due to their broad spectrum of activity and act as effective treatment against multi-drug resistance pathogens. In this study, we have used an AMP, RW20 (1RPVKRKKGWPKGVKRGPPKW20). RW20 peptide is derived from the histone acetyltransferases (HATs) of the freshwater teleost, Channa striatus. The antimicrobial prediction tool has been utilized to identify the RW20 sequence from the HATs sequence. We synthesized the peptide to explore its mechanism of action. In an in vitro assay, RW20 was challenged against P. aeruginosa and we showed that RW20 displayed antibacterial properties and damaged the cell membrane. The mechanism of action of RW20 against P. aeruginosa has been established via field emission scanning electron microscopy (FESEM) as well as fluorescence assisted cell sorter (FACS) analysis. Both these experiments established that RW20 caused bacterial membrane disruption and cell death. Moreover, the impact of RW20, in-vivo, was tested against P. aeruginosa-infected zebrafish larvae. In the infected larvae, RW20 showed protective effect against P. aeruginosa by increasing the larval antioxidant enzymes, reducing the excess oxidative stress and apoptosis. Thus, it is possible that HATs-derived RW20 can be an efficient antimicrobial molecule against P. aeruginosa.

White feces syndrome in shrimp: Comprehensive understanding of immune system responses.

White feces syndrome (WFS) is a multifactorial disease that affects global shrimp production. The diagnostic approach to identify WFS involves traditional and molecular scientific methods by examining histopathology, bioassays, PCR (polymerase chain reaction), and calorimetric estimation. The pathogenesis of WFS is closely associated with Vibrio spp., intestinal microbiota (IM) dysbiosis, and Enterocytozoon hepatopenaei (EHP). It also has caused over 10-15 % loss in the aquaculture industry and is also known to cause retardation, lethargy and slowly leading to high mortality in shrimp farms. Therefore, it is necessary to understand the molecular mechanisms processed under the association of IM dysbiosis, Vibrio spp., and EHP to analyze the impact of disease on the innate immune system of shrimp. However, only very few reviews have described the molecular pathways involved in WFS. Hence, this review aims to elucidate an in-depth analysis of molecular pathways involved in the innate immune system of shrimp and their response to pathogens. The analysis and understanding of the impact of shrimp's innate immune system on WFS would help in developing treatments to prevent the spread of disease, thereby improving the economic condition of shrimp farms worldwide.

Multifunctional curcumin mediated zinc oxide nanoparticle enhancing biofilm inhibition and targeting apoptotic specific pathway in oral squamous carcinoma cells.

BACKGROUND: Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties. METHODS: In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity. RESULTS: ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40 µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10 µg/mL, 20 µg/mL, 40 µg/mL, and 80 µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells. CONCLUSIONS: This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.

Impact of butylparaben on ß-cell damage and insulin/PEPCK expression in zebrafish larvae: Protective effects of morin.

Butylparaben (BP), a common chemical preservative in cosmetic and pharmaceutical products, has been known to induce oxidative stress and disrupt endocrine function in humans. In contrast, morin, a flavonoid derived from the Moraceae family, exhibits diverse pharmacological properties, including anti-inflammatory and antioxidant. Despite this, the protective role of morin against oxidative stress-induced damage in pancreatic islets remains unclear. Therefore, in this study, we aimed to investigate the potential protective mechanism of morin against oxidative stress-induced damage caused by BP in zebrafish larvae. To achieve this, we exposed the zebrafish larvae to butylparaben (2.5 mg/L) for 5 days, leading to increased oxidative stress and apoptosis in ß-cells. However, our compelling findings revealed that pretreatment with various concentrations of morin effectively reduced mortality and mitigated apoptosis and lipid peroxidation in ß-cells induced by BP exposure. In addition, zebrafish larvae exposed to BP for 5 days exhibited evident ß-cell damage. However, the pretreatment with morin showed promising effects by promoting ß-cell proliferation and lowering glucose levels. Furthermore, gene expression studies indicated that morin pretreatment normalized PEPCK expression while increasing insulin expression in BP-exposed larvae. In conclusion, our findings highlight the potential of morin as a protective agent against BP-induced ß-cell damage in zebrafish larvae. The observed improvements in oxidative stress, apoptosis, and gene expression patterns support the notion that morin could be further explored as a therapeutic candidate to counteract the detrimental effects of BP exposure on pancreatic ß-cells.

Interconnected environmental challenges: heavy metal-drug interactions and their impacts on ecosystems.

Industrial expansion and inadequate environmental safety measures are major contributors to environmental contamination, with heavy metals (HMs) and pharmaceutical waste playing crucial roles. Their negative effects are most noticeable in aquatic species and vegetation, where they accumulate in tissues and cause harmful results. Interactions between HMs and pharmaceutical molecules result in the production of metal-drug complexes (MDCs), which have the potential to disturb diverse ecosystems and their interdependence. However, present studies frequently focus on individual pollutants and their effects on specific environmental parameters, leaving out the cumulative effects of pollutants and their processes across several environmental domains. To address this gap, this review emphasizes the environmental sources of HMs, elucidates their emission pathways during anthropogenic activities, investigates the interactions between HMs and pharmaceutical substances, and defines the mechanisms underlying the formation of MDCs across various ecosystems. Furthermore, this review underscores the simultaneous occurrence of HMs and pharmaceutical waste across diverse ecosystems, including the atmosphere, soil, and water resources, and their incorporation into biotic organisms across trophic levels. It is important to note that these complex compounds represent a higher risk than individual contaminants.

Cadmium and ketoprofen accumulation influences aquatic ecosystem demonstrated using in-vivo zebrafish model.

The growing concern about pollution and toxicity in aquatic as well as terrestrial organisms is predominantly caused due to waterborne exposure and poses a risk to environmental systems and human health. This study addresses the co-toxic effects of cadmium (Cd) and ketoprofen (KPF), representing heavy metal and pharmaceutical discharge pollutants, respectively, in aquatic ecosystems. A 96-h acute toxicity assessment was conducted using zebrafish embryos. The results indicated that high dosages of KPF (10, 15, and 100 µg/mL) and Cd (10 and 15 µg/mL) reduced survivability and caused concentration-dependent deformities such as scoliosis and yolk sac edema. These findings highlight the potential defects in development and metabolism, as evidenced by hemolysis tests demonstrating dose-dependent effects on blood cell integrity. Furthermore, this study employs adult zebrafish for a 42-day chronic exposure to Cd and KPF (10 and 100 µg/L) alone or combined (10 + 10 and 100 + 100 µg/L) to assess organ-specific Cd and KPF accumulation in tissue samples. Organ-specific accumulation patterns underscore complex interactions impacting respiratory, metabolic, and detoxification functions. Prolonged exposure induces reactive oxygen species formation, compromising antioxidant defense systems. Histological examinations reveal structural changes in gills, gastrointestinal, kidney, and liver tissues, suggesting impairments in respiratory, osmoregulatory, nutritional, and immune functions. This study emphasizes the importance of conducting extensive research on co-toxic effects to assist with environmental risk assessments and safeguard human health and aquatic ecosystems.

Mitigating microplastic pollution: A critical review on the effects, remediation, and utilization strategies of microplastics.

Microplastics are found ubiquitous in the natural environment and are an increasing source of worry for global health. Rapid industrialization and inappropriate plastic waste management in our daily lives have resulted in an increase in the amount of microplastics in the ecosystem. Microplastics that are <150 µm in size could be easily ingested by living beings and cause considerable toxicity. Microplastics can aggregate in living organisms and cause acute, chronic, carcinogenic, developmental, and genotoxic damage. As a result, a sustainable approach to reducing, reusing, and recycling plastic waste is required to manage microplastic pollution in the environment. However, there is still a significant lack of effective methods for managing these pollutants. As a result, the purpose of this review is to convey information on microplastic toxicity and management practices that may aid in the reduction of microplastic pollution. This review further insights on how plastic trash could be converted as value-added products, reducing the load of accumulating plastic wastes in the environment, and leading to a beneficial endeavor for humanity.

Textile azo dye, Sudan Black B, inducing hepatotoxicity demonstrated in in vivo zebrafish larval model.

Environmental pollution, particularly from textile industry effluents, raises concerns globally. The aim of this study is to investigate the hepatotoxicity of Sudan Black B (SBB), a commonly used textile azo dye, on embryonic zebrafish. SBB exposure led to concentration-dependent mortality, reaching 100% at 0.8 mM, accompanied by growth retardation and diverse malformations in zebrafish. Biochemical marker analysis indicated adaptive responses to SBB, including increased SOD, CAT, NO, and LDH, alongside decreased GSH levels. Liver morphology analysis unveiled significant alterations, impacting metabolism and detoxification. Also, glucose level was declined and lipid level elevated in SBB-exposed in vivo zebrafish. Inflammatory gene expressions (TNF-α, IL-10, and INOS) showcased a complex regulatory interplay, suggesting an organismal attempt to counteract pro-inflammatory states during SBB exposure. The increased apoptosis revealed a robust hepatic cellular response due to SBB, aligning with observed liver tissue damage and inflammatory events. This multidimensional study highlights the intricate web of responses due to SBB exposure, which is emphasizing the need for comprehensive understanding and targeted mitigation strategies. The findings bear the implications for both aquatic ecosystems and potentially parallels to human health, underscoring the imperative for sustained research in this critical domain.

Piperine-coated zinc oxide nanoparticles target biofilms and induce oral cancer apoptosis via BCl-2/BAX/P53 pathway.

BACKGROUND: Dental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these pathogens and oral cancer initiation and progression. Innovative therapeutic approaches are needed due to antibiotic resistance concerns and treatment limitations. METHODS: We synthesized and analyzed piperine-coated zinc oxide nanoparticles (ZnO-PIP NPs) using UV spectroscopy, SEM, XRD, FTIR, and EDAX. Antioxidant and antimicrobial effectiveness were evaluated through DPPH, ABTS, and MIC assays, while the anticancer properties were assessed on KB oral squamous carcinoma cells. RESULTS: ZnO-PIP NPs exhibited significant antioxidant activity and a MIC of 50 µg/mL against dental pathogens, indicating strong antimicrobial properties. Interaction analysis revealed high binding affinity with dental pathogens. ZnO-PIP NPs showed dose-dependent anticancer activity on KB cells, upregulating apoptotic genes BCL2, BAX, and P53. CONCLUSIONS: This approach offers a multifaceted solution to combatting both oral infections and cancer, showcasing their potential for significant advancement in oral healthcare. It is essential to acknowledge potential limitations and challenges associated with the use of ZnO NPs in clinical applications. These may include concerns regarding nanoparticle toxicity, biocompatibility, and long-term safety. Further research and rigorous testing are warranted to address these issues and ensure the safe and effective translation of ZnO-PIP NPs into clinical practice.

Luteolin, a promising quorum quencher mitigates virulence factors production in Pseudomonas aeruginosa - In vitro and In vivoapproach.

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes healthcare-associated infection and high mortality in immunocompromised patients. It produces several virulence factors through quorum sensing (QS) mechanisms that is essential for subverting host immune system. Even front-line antibiotics are unable to control PA pathogenicity due to the emergence of antibiotic resistance. Luteolin is a naturally derived compound that has proven to be the effective drug to annihilate pathogens through quorum quenching mechanism. In this study, the protective effect of luteolin against the PA-mediated inflammation was demonstrated using zebrafish model. Luteolin protects zebrafish from PA infection and increases their survival rate. It was found that PA-mediated ROS, lipid peroxidation, and apoptosis were also significantly reduced in luteolin-treated zebrafish larvae. Open field test (OFT) reveals that luteolin rescued PA-infected zebrafish from retarded swimming behavior. Furthermore, luteolin increases SOD and CAT levels and decreases LDH and NO levels in PA-infected zebrafish compare to control group. Histological and gene expression analysis reveals that luteolin protects PA-infected zebrafish by decreasing gut inflammation and altering the expression of inflammatory (TNF-α, IL-1ß, IL-6) and antioxidant markers (iNOS, SOD, CAT). Thus, luteolin was found to have dual effect in protecting PA-infected zebrafish by decreasing virulence factors production in PA and stimulating host immune system. This is the first study demonstrating the protective effect of luteolin using animal model. Hence, luteolin could be used as a future therapeutic drug to control multi-drug resistant PA.

Unveiling nanotubes-mediated communication: Enterococcus faecalis countering Salmonella ser. Typhi - In vitro and In vivo insights.

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-1ß, 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.

Role and mechanistic actions of protein kinase inhibitors as an effective drug target for cancer and COVID.

Kinases can be grouped into 20 families which play a vital role as a regulator of neoplasia, metastasis, and cytokine suppression. Human genome sequencing has discovered more than 500 kinases. Mutations of the kinase itself or the pathway regulated by kinases leads to the progression of diseases such as Alzheimer's, viral infections, and cancers. Cancer chemotherapy has made significant leaps in recent years. The utilization of chemotherapeutic agents for treating cancers has become difficult due to their unpredictable nature and their toxicity toward the host cells. Therefore, targeted therapy as a therapeutic option against cancer-specific cells and toward the signaling pathways is a valuable avenue of research. SARS-CoV-2 is a member of the Betacoronavirus genus that is responsible for causing the COVID pandemic. Kinase family provides a valuable source of biological targets against cancers and for recent COVID infections. Kinases such as tyrosine kinases, Rho kinase, Bruton tyrosine kinase, ABL kinases, and NAK kinases play an important role in the modulation of signaling pathways involved in both cancers and viral infections such as COVID. These kinase inhibitors consist of multiple protein targets such as the viral replication machinery and specific molecules targeting signaling pathways for cancer. Thus, kinase inhibitors can be used for their anti-inflammatory, anti-fibrotic activity along with cytokine suppression in cases of COVID. The main goal of this review is to focus on the pharmacology of kinase inhibitors for cancer and COVID, as well as ideas for future development.

Expanding germ-organ theory: Understanding non-communicable diseases through enterobacterial translocation.

Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.

Deacetyl epoxyazadiradione protects aminoglycoside antibiotic-induced renal cell apoptosis, in vitro.

Aminoglycoside antibiotics such as gentamicin are used frequently to treat bacterial infections in humans. Excessive consumption of these antibiotics lead to renal dysfunction. One of the factors contributing to renal dysfunction is oxidative damage, which causes apoptosis. Hence, this study investigates the effect of the antioxidant compound deacetyl epoxyazadiradione (DEA) in reducing cell death induced by gentamicin treatment in kidney cells (Madin-Darby canine kidney cells). The antioxidant experiments showed that reactive oxygen species level is decreased up to 27.06 ± 0.18% in 150 µM of DEA treatment. At this concentration, the activity of antioxidant enzymes such as superoxide dismutase increased from 0.4 ± 0.04 to 1.46 ± 0.05 µmol/min/L and catalase increased from 7.48 ± 0.39 to 17.6 ± 0.74 U/mg. The relative folds of gene expression of mitochondrial enzymes such as GST, GPx and GR restored from 0.596 ± 0.019, 0.521 ± 0.013 and 0.775 ± 0.014 to 0.866 ± 0.013, 0.669 ± 0.015 and 0.8615 ± 0.028, respectively. Consequently, the percentage of cell viability increases upto 91.8 ± 2.01 from 61.93 ± 1.63 with much less fragmentation in genomic DNA. Additionally, molecular docking results showed that DEA could bind to Bax, Bcl- 2, Caspase- 3 and Caspase- 9 proteins. These results indicate that DEA could reduce cell apoptosis by reducing oxidative stress due to antibiotics and interrupting the apoptotic signal pathway in kidney cells.

Insights into molecular aspects of pathogenesis and disease management in acute hepatopancreatic necrosis disease (AHPND): An updated review.

Shrimp aquaculture is a rapidly growing sector that makes a significant economic contribution. However, the aquaculture industry is confronted with significant challenges, and infectious diseases, notably Acute Hepatopancreatic Necrosis Disease (AHPND), have emerged as severe threat. AHPND is caused by pathogens carrying the pVA-1 plasmid, which expresses the PirAB toxin, and it has wreaked havoc in shrimp aquaculture, imposing substantial economic burdens. To address this issue, it is crucial to delve into shrimp's immune responses. Therefore, this comprehensive review offers an in-depth examination of AHPND outbreaks, encompassing various facets such as environmental factors, host susceptibility, and the mechanisms employed by the pathogens. Traditional approaches to combat AHPND, primarily relying on chemicals and antibiotics, have raised concerns related to antibiotic resistance and have demonstrated limited success in disease control. Hence this review spotlights recent advancements in molecular diagnostics, therapeutic agents, and research related to shrimp immunity. Understanding these developments is crucial in the ongoing battle against AHPND. In conclusion, this review underscores the pressing need to comprehend the underlying mechanisms of AHPND pathogenesis and emphasizes the importance of developing comprehensive and effective solutions to combat this devastating disease, which continues to threaten the sustainability of shrimp farming.

Circular RNA ciRS-7 signature as a potential biomarker for the early detection of diabetes with Alzheimer's disease: a hypothesis.

In the 1970s, Circular RNAs (CircRNAs) were first discovered in RNA viruses as viroids and were initially assumed to be RNA splicing defects. The roles and topologies of these circular RNA loops were later revealed using computer analysis and RNA-sequencing. They were found to demonstrate various functions, including protein scaffolding, parental gene regulation, microRNA sponges, and RNA-protein interactions. CircRNAs play a crucial role in controlling gene expression and are essential for biological development and illness detection, as demonstrated by their roles as miRNA sponges, endogenous RNAs, and potential biomarkers. Insulin resistance is caused by damage to ß-cells in the pancreatic islets, which reduces the body's response to the hormone insulin. This reduction in insulin response hinders glucose from entering cells and providing energy for critical processes. As a result, insulin-resistant cells elevate blood sugar levels, leading to diabetes. Diabetes, in turn, increases the risk of heart disease and stroke, which can damage the heart and arteries. Additionally, an excess of insulin can impact the brain's chemical balance, contributing to the development of Alzheimer's disease. Furthermore, oxidative stress created by damaged pancreatic cells during high blood sugar conditions may lead to the destruction of brain cells and the onset of Alzheimer's disease. The hypothesis of this review is to provide an overview of the most dominant ciRS-7 circRNA identified in pancreatic islet cell dysfunction and neurologic disorders, such as Alzheimer's disease. By considering ciRS-7 circRNA as a potential biomarker for diabetes, early detection and treatment of diabetes may be facilitated, potentially reducing the risk of Alzheimer's disease onset in the future.

Brain targeted luteolin-graphene oxide nanoparticle abrogates polyethylene terephthalate induced altered neurological response in zebrafish.

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.

Nimbin (N1) and analog N3 from the neem seeds suppress the migration of osteosarcoma MG-63 cells and arrest the cells in a quiescent state mediated via activation of the caspase-modulated apoptotic pathway.

BACKGROUND: Natural products are considered effective sources for new therapeutic research and development. The numerous therapeutic properties of natural substances in traditional medicine compel us to investigate the anti-cancer properties of Nimbin (N1) and its semi-natural analog Nimbic acid (N3) from Azadirachta indica against MG-63 Osteosarcoma cells. MATERIALS AND METHODS: The therapeutic efficacy of N1 and N3 were screened for their toxicity and cytotoxic activity using L6 myotubes, zebrafish larvae and MG-63 osteosarcoma cells. The mitochondrial membrane potential was evaluated using the Rhodamine 123 stain. Further, the nuclear and cellular damage was distinguished using Hoechst and Acridine orange/EtBr stain. The mechanism of cell cycle progression, cellular proliferation and caspase cascade activation was screened using scratch assay, flow cytometry, and mRNA expression analysis. RESULTS: The Nimbin and analogue N3 were found to be non-toxic to normal L6 cells (Rat skeletal muscles), exhibited cytotoxicity in MG-63 cells, and were exposed to be an active inhibitor of cell proliferation and migration. Analogs N1 and N3 induced negative mitochondrial membrane potential when stained with Rhodamine 123, leading to nuclear damage and apoptosis stimulation using AO/EtBr and Hoechst. Further, N1 and N3 induced cell cycle arrest in G0/G1 phase in flow cytometry using PI staining and induced apoptosis by activating the caspase cascade and upregulated Caspase 3 and caspase 9. CONCLUSION: The study demonstrated cytotoxic activity against MG-63 osteosarcoma cells while being non-toxic to normal L6 cells. These compounds inhibited cell proliferation and migration, induced mitochondrial dysfunction, nuclear damage, and apoptosis stimulation. Furthermore, N1 and N3 caused cell cycle arrest and activated the caspase cascade, ultimately leading to apoptosis. These findings indicate that N1 and N3 hold promise as potential candidates used alone or combined with existing drugs for further investigation and development as anti-cancer agents.

Advancements of fish-derived peptides for mucormycosis: a novel strategy to treat diabetic compilation.

Mucormycosis, an extremely fatal fungal infection, is a major hurdle in the treatment of diabetes consequences. The increasing prevalence and restricted treatment choices urge the investigation of novel therapeutic techniques. Because of their effective antimicrobial characteristics and varied modes of action, fish-derived peptides have lately emerged as viable options in the fight against mucormycosis. This review examines the potential further application of fish-derived peptides in diagnosing and managing mucormycosis in relation to diabetic complications. First, we examine the pathophysiology of mucormycosis and the difficulties in treating it in diabetics. We emphasize the critical need for alternative therapeutic methods for tackling the limitations of currently available antifungal medicines. The possibility of fish-derived peptides as an innovative approach to combat mucormycosis is then investigated. These peptides, derived from several fish species, provide wide antimicrobial properties against a variety of diseases. They also have distinct modes of action, such as rupture of cell membranes, suppression of development, and modification of the host immunological response. Furthermore, we investigate the problems and prospects connected with the clinical application of fish-derived peptides. Ultimately, future advances in fish-derived peptides, offer interesting avenues for the management of mucormycosis in the context of diabetic comorbidities. More research and clinical trials are needed to properly investigate these peptide's therapeutic potential and pave the way for their adoption into future antifungal therapies.