Mitigating phthalate toxicity: The protective role of humic acid and clay in zebrafish larvae.

This research study aimed to explore the mitigating effects of humic acid and clay on the toxicity induced by three different phthalates (DBP, DEP, DEHP) on zebrafish larvae growth. Prolonged exposure to DBP resulted in a concerning 87.33% mortality rate, significantly reduced to 7.3% when co-administered with humic acid. A similar reduction in mortality was observed for the other two phthalates (DEP and DEHP). Additionally, the introduction of phthalates with humic acid, clay, or their combination led to a significant decrease in the malformation rate in larvae. High-Performance Liquid Chromatography (HPLC) analysis of phthalates in treatments revealed a noteworthy decline in their concentration when combined with humic acid and clay. This suggests a reduced bioavailability of phthalates to larvae, aligning with diminished toxicity, lower mortality, fewer malformations, and improved organ development, as well as less oxidative stress. Furthermore, measurements of larval length and morphological scoring affirmed the protective role of humic acid and clay in promoting the normal growth of zebrafish. This study underscores the potential of environment modulators, such as humic acid and clay, as effective bioremediation agents against phthalate toxicity. The generation of reactive oxygen species (ROS), indicative of oxidative stress, was markedly higher in larvae treated solely with phthalates compared to the control. Conversely, larvae treated with a combination of phthalates and humic acid or clay exhibited a significant decrease in ROS generation, signaling a decline in oxidative stress. Histopathological analysis of adult fish subjected to various treatments revealed significant damage to vital organs like the liver and intestine when treated with phthalates alone. However, when phthalates were introduced with humic acid, clay, or both, the morphology closely resembled that of the control, reinforcing the protective role of humic acid and clay in zebrafish development against administered phthalates.

Formation, characterization, and analysis of curcumin nanoformulation for evaluating its in vitro cytotoxicity.

Nanotechnology holds significance in all fields of research, and the formation and surface alterations of nanomaterials are particularly important in this discipline. Nanoformulations synthesized with bioactive plant components play a crucial role in the improvement of several therapeutics and diagnostics. In the present study, we reported the synthesis of a curcumin nanoformulation (CN) by using curcumin and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The synthesized CN was characterized using dynamic light scattering, UV-Visible spectrophotometry, Fourier-transform infrared spectroscopy, field-emission scanning electron microscopy, and X-ray diffraction. Furthermore, it was evaluated for solubility, drug loading, encapsulation efficiency, stability, in vitro release, and anticancer potentials. The role of TPGS in the synthesis of CN was validated. The synthesized CN exhibited a size of 6.2 ± 1.9 nm, needle-shaped morphology, a polydispersity index of 0.164, and zeta potential of - 10.1 ± 3.21 mV, as determined by characterization techniques. Its water solubility was 2.5 × 104 times higher than that of pure curcumin. The encapsulation efficiency and curcumin loading efficiency of the synthesized CN were found to be 80 and 10%, respectively, with storage stability exceeding 30 days. Moreover, the synthesized CN demonstrated significant in vitro anticancer activity against the colorectal cancer cell line HCT-116, with an IC50 value of 12.74 ± 0.54 µM at 24 h.

Spatiotemporal dynamics of DNA nanocage uptake in zebrafish embryos for targeted tissue bioimaging applications.

Three-dimensional DNA nanocages have attracted significant attention for various biomedical applications including targeted bioimaging in vivo. Despite the numerous advantages, the use and in vivo exploration of DNA nanocages are limited as the cellular targeting and intracellular fate of these DNA nanocages within various model systems have not been explored well. Herein, using a zebrafish model system, we provide a detailed understanding of time-, tissue- and geometry-dependent DNA nanocage uptake in developing embryos and larvae. Of all the geometries tested, tetrahedrons showed significant internalization in 72 hours post-fertilized larvae upon exposure, without disturbing the expression of genes involved in embryo development. Our study provides a detailed understanding of the time and tissue-specific uptake of DNA nanocages in the zebrafish embryos and larvae. These findings will provide valuable insights into the internalization and biocompatible potential of DNA nanocages and will help to predict their candidature for biomedical applications.

Fabrication, assessment, and potential anti-bacterial activity of sandalwood oil nanoemulsion and its hand rub sanitizer.

In the last decade, extensive research has been performed on developing hand sanitizers that can be used to eradicate the diseases that are caused due to poor hand hygiene. Essential oils possess antibacterial and antifungal properties and thus have great potential to replace the available antibacterial agents. In the present study, sandalwood oil-based nanoemulsion (NE) and sanitizer have been formulated and well characterized for their properties. Antibacterial activity was assessed using growth inhibition studies, agar cup, viability assay, etc. The sandalwood oil NE synthesized had oil to surfactant ratio of 1:0.5 (2.5% sandalwood oil and 0.5% Tween 80) and was observed to have a droplet diameter of 118.3 ± 0.92 nm, the zeta potential of - 18.8 ± 2.01 mV, and stability of 2 months. The antibacterial activity of sandalwood NE and sanitizer was evaluated against microorganisms. The antibacterial activity was assessed using the zone of inhibition value of sanitizer, which was in the range of 19 to 25 mm against all microorganisms. Morphological analysis showed distant changes in membrane shape and size and microorganisms' morphology. The synthesized NE was thermodynamically stable and efficient enough to be used in sanitizer, and the formulated sanitizer showed great antibacterial efficacy.

New insight into long-term effects of phthalates microplastics in developing zebrafish: Evidence from genomic alteration and organ development.

The plasticizer leaches from the microplastics are one of the significant concerns related to plastic pollution. These plasticizers are known to be endocrine disrupters; however, little is known about their long-term effect on the development of aquatic vertebrates. Hence, the present study has been conducted to provide a holistic understanding of the effect of the three most common plasticizers, dibutyl phthalate (DBP), diethyl phthalate (DEP), and di-ethylhexyl phthalate (DEHP) leaching out from the microplastics in zebrafish development. Zebrafish larvae were exposed to different phthalates at different concentrations. The phthalates have shown significantly higher mortality and morphological changes in the larva upon exposure compared to the control. A significant change in the genes related to cardiovascular development (krit1, fbn2b), dorsoventral axis development (chrd, smad5), tail formation (pkd2, wnt3a, wnt8a), and floorplate development (foxa2) were also observed under the effects of the phthalates in comparison to control.

Development of food-grade antimicrobials of fenugreek oil nanoemulsion-bioactivity and toxicity analysis.

Antimicrobials of natural origin are proving to be an effective solution to emerging antimicrobial resistance and its physiological side effects. Recent studies have demonstrated that essential oils encapsulated in the form of nanoemulsions have better antimicrobial activity than the oil itself, possibly due to its high stability, solubility, sustained release, and increased bioavailability. In the present study, fenugreek oil-a well-known antimicrobial and antioxidant-has been used to fabricate nanoemulsion (NE), with an objective to meet potential alternative to synthesized antimicrobials. A combination of three different components, water, fenugreek oil, and Tween 80, has been used to prepare the nanoemulsions of different size and one of the most stable nanoemulsion with lowest concentration of surfactant Tween 80 was used to assess its bioactivity, antimicrobial properties, and toxicity against human hepatic cell line. Among all the formulations, nano-emulsion with 2.5% oil concentration, 30 min sonication (hydrodynamic size 135.2 nm, zeta potential 36.8 mV, PDI 0.135, and pH 5.12), was selected for all studies. The nanoemulsion showed potential antibacterial activity against all the microbial strains (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa) used in this study. Interestingly, the nanoemulsion showed potential antibacterial activity against P. aeruginosa, known to show resistance against ampicillin. The toxicity evaluation in human hepatic cell line (WRL-68) indicated no significant toxicity of nanoemulsion up to the concentration of 800 µg/ml. The synthesized nanoemulsion thus has a translational potential as a food-grade non-toxic natural nanoantimicrobials.

NIR-Active Porphyrin-Decorated Lipid Microbubbles for Enhanced Therapeutic Activity Enabled by Photodynamic Effect and Ultrasound in 3D Tumor Models of Breast Cancer Cell Line and Zebrafish Larvae.

Porphyrin is known to enable the photodynamic effect during cancer drug delivery and molecular imaging. However, its hydrophobicity and tendency to aggregate in an aqueous medium create a significant hurdle for its use as an anticancer drug. Loading porphyrin onto biocompatible delivery vehicles can enhance its efficacy. This can be achieved by using gas-filled microbubbles that can be administered intravenously. This study aimed at developing near-infrared (NIR)-active porphyrin-loaded lipid microbubbles with anticancer activity enhanced by sonodynamic and photodynamic effects. The porphyrin-loaded microbubbles were studied for their cell toxicity, cellular uptake of porphyrin, and effect on cellular three-dimensional (3D) invasion of breast cancer cells (MDA-MB-231) in cellulo. Toxicity studies in zebrafish larvae (Danio rerio) in the presence and absence of photodynamic and sonodynamic therapy were also conducted. The results suggest that with a higher concentration of porphyrin loaded on microbubbles, the porphyrin-loaded microbubbles display a higher therapeutic effect facilitated by photodynamic and sonodynamic therapy, which results in enhanced cellular uptake and cellular toxicity. A lower concentration of loaded porphyrin microbubbles exhibits high cellular viability and good fluorescence intensity in the NIR region, which can be exploited for bioimaging applications.

Stopping the Unstoppable: Unconventional Methods to Prevent the Biofilm Growth.

Biofilms are consortia of microorganisms encased in extracellular matrix that protect cells from adverse conditions. A biofilm matrix is typically composed of extracellular DNA, cellulose and proteinaceous amyloid fibers. The matrix aids in adhesion to abiotic and biotic surface including medical devices and host tissues. The presence of biofilm makes bacteria more resilient and non-responsive to most current treatment regimes at disposal. Therefore, biofilm-associated infections are serious threat in hospital settings and pose a huge burden on economy. Inhibition of matrix components (cellulose and/or amyloid formation) has emerged as a lucrative alternative strategy to cure biofilm-related infections and combat antibiotic resistance. Here we review the current and emerging therapeutic interventions to mitigate persistent infections due to biofilms. The successful implementation of these interventions will have a huge impact on alleviating the current financial burden on healthcare services.