Aspartame Causes Developmental Defects and Teratogenicity in Zebra Fish Embryo: Role of Impaired SIRT1/FOXO3a Axis in Neuron Cells.

Aspartame, a widely used artificial sweetener, is present in many food products and beverages worldwide. It has been linked to potential neurotoxicity and developmental defects. However, its teratogenic effect on embryonic development and the underlying potential mechanisms need to be elucidated. We investigated the concentration- and time-dependent effects of aspartame on zebrafish development and teratogenicity. We focused on the role of sirtuin 1 (SIRT1) and Forkhead-box transcription factor (FOXO), two proteins that play key roles in neurodevelopment. It was found that aspartame exposure reduced the formation of larvae and the development of cartilage in zebrafish. It also delayed post-fertilization development by altering the head length and locomotor behavior of zebrafish. RNA-sequencing-based DEG analysis showed that SIRT1 and FOXO3a are involved in neurodevelopment. In silico and in vitro analyses showed that aspartame could target and reduce the expression of SIRT1 and FOXO3a proteins in neuron cells. Additionally, aspartame triggered the reduction of autophagy flux by inhibiting the nuclear translocation of SIRT1 in neuronal cells. The findings suggest that aspartame can cause developmental defects and teratogenicity in zebrafish embryos and reduce autophagy by impairing the SIRT1/FOXO3a axis in neuron cells.

Brown sugar as a carbon source can make agricultural organic waste compost enter the secondary thermophilic stage and promote compost decomposition.

To enhance the efficiency of composting agricultural organic waste (AOW), this study aimed to examine the impact of inoculating tomato straw compost with two distinct microbial agents: ZymoZone (ZZ), a composite microbial agent derived from the straw compost and Effective Microorganisms (EM), a commercial microbial agent. Furthermore, in order to reactivate the microorganisms within the compost during the initial high temperature phase, 10% brown sugar was introduced as a carbon source. The objective of this addition was to assess its influence on the composting process. The findings revealed that compared to the control (CK) group, the ZZ and EM treatments extended the first high-temperature phase by 2 and 1 day, respectively. Furthermore, with the addition of 10% brown sugar, the ZZ and EM treatments remained in the second high-temperature phase for 8 and 7 days, respectively, while the CK treatment had already entered the cooling stage by then. Notably, the inoculation of microbial agents and the addition of brown sugar substantially augmented the activity of lignocellulose-related hydrolases, thereby promoting the degradation of lignocellulose in the ZZ and EM treatment groups. This was confirmed by FTIR analysis, which demonstrated that the addition of microbial agents facilitated the degradation of specific substances, leading to reduced absorbance in the corresponding spectra. XRD analysis further indicated a notable reduction in cellulose crystallinity for both the ZZ (8.00%) and EM (7.73%) treatments. Hence, the incorporation of microbial agents and brown sugar in tomato straw compost effectively enhances the composting process and improves the quality of compost products.

Recent Prospects of Carbonaceous Nanomaterials-Based Laccase Biosensor for Electrochemical Detection of Phenolic Compounds.

Phenolic compounds (PhCs) are ubiquitously distributed phytochemicals found in many plants, body fluids, food items, medicines, pesticides, dyes, etc. Many PhCs are priority pollutants that are highly toxic, teratogenic, and carcinogenic. Some of these are present in body fluids and affect metabolism, while others possess numerous bioactive properties such as retaining antioxidant and antimicrobial activity in plants and food products. Therefore, there is an urgency for developing an effective, rapid, sensitive, and reliable tool for the analysis of these PhCs to address their environmental and health concern. In this context, carbonaceous nanomaterials have emerged as a promising material for the fabrication of electrochemical biosensors as they provide remarkable characteristics such as lightweight, high surface: volume, excellent conductivity, extraordinary tensile strength, and biocompatibility. This review outlines the current status of the applications of carbonaceous nanomaterials (CNTs, graphene, etc.) based enzymatic electrochemical biosensors for the detection of PhCs. Efforts have also been made to discuss the mechanism of action of the laccase enzyme for the detection of PhCs. The limitations, advanced emerging carbon-based material, current state of artificial intelligence in PhCs detection, and future scopes have also been summarized.

Protective efficacy of naringenin against cadmium-induced redox imbalance in Labeo rohita: an integrated biomarker approach.

The protective efficacy of dietary naringenin (NG) has been investigated against the toxicity caused by cadmium chloride (CdCl2) using biomarkers of oxidative stress in the liver, gills and kidney of Labeo rohita. The fish were exposed to environmentally relevant concentrations of CdCl2 (0.37 and 0.62 mg/L) and simultaneously orally administered with NG (50 mg/kg bw/day) for 60 days. Tissue (gills, liver and kidney) samples were collected on days 15, 30 and 60 of the experiment and analysed for endogenous antioxidants and oxidative stress biomarkers. CdCl2 exposure for 15 and 30 days induced the development of adaptive mechanism as demonstrated by the enhanced activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in all three tissues. However, on the 60th day, CdCl2-induced oxidative damage was stipulated by a decline in the enzyme activities and reduced glutathione (GSH) content significantly (p < 0.05) below control levels along with enhanced levels of lipid peroxidation. Oral administration of NG in toxicant exposed fish significantly restored the altered levels of antioxidants, oxidative enzymes and lipid peroxidation. Besides, integrated biomarker response (IBR) analysis was applied by combining all the biomarkers to indicate the overall stress response index. IBR analysis confirmed the altered levels of biomarkers, the oxidative stress induced by CdCl2 exposure and the ameliorative potential of NG. The present study suggested that NG might have protective role against Cd-induced oxidative insult which might be ascribed to the ability of NG to chelate metals and scavenge free radicals.

Ameliorating effect of ascorbic acid on fenvalerate induced ultrastructural changes in scales, erythrocytes and gills of Ctenopharyngodon idella (Valenciennes, 1844).

Fenvalerate (type II synthetic pyrethroid), widely used in agricultural practices, find its way into aquatic ecosystem through air, by runoff, or by percolation to groundwater. It is an extremely toxic insecticide for aquatic organisms especially fish. In the present study, the fenvalerate (FEN) induced toxicity and the protective efficacy of ascorbic acid (AA) against FEN in Ctenopharyngodon idella was evaluated by studying the structural alterations in scales, erythrocytes and gills. The fishes were exposed to 1.2 µg/L and 2 µg/L of FEN and orally administered with 1000 mg/kg diet of AA. The fishes were scrutinized on 15th, 30th and 60th day of experiment. Scanning electron microscopic studies (SEM) of FEN-treated fish revealed extensive morphological alterations on the microstructure of scales including deformed focus, uprooted lepidonts and tubercles, hole formation and worn out calcareous material from the surface. FEN intoxication induced severe damage on erythrocytes including formation of dacrocytes, serrated spherocytes, echinocytes with oozed out cytoplasmic content, contracted plasma membrane and appearance of lobopodial projections. Ultrastructural studies in gills declared profound lesions in the form of aneurysm, loss of secondary lamellae and destructed microstructures of pavement cells. On the other hand, supplementation of AA in diet mitigated the impairment provoked by FEN on the scales, erythrocytes and gills due to its antioxidant properties.

In vivo genotoxicity and cytotoxicity assessment of cadmium chloride in peripheral erythrocytes of Labeo rohita (Hamilton).

Cadmium chloride (CdCl2) induced genotoxicity and cytotoxicity has been assessed in the peripheral blood erythrocytes of freshwater fish Labeo rohita exposed to 0.37 and 0.62mg/L of CdCl2 in water for 100 days. The blood samples of the fish were collected at different intervals (days 1, 3, 5, 10, 15, 30, 60 and 100) of exposure period to analyze DNA damage using comet assay and the occurrence of micronuclei and other cellular anomalies. The results of comet assay showed a significant increase in the mean percentage of tail DNA at both the concentrations. Exposure to CdCl2 also induced micronuclei in addition to many nuclear abnormalities such as nuclear bud, binucleates, lobed, notched and vacuolated nuclei. Cytoplasmic abnormalities like echinocytes, acanthocytes, notched, microcytes and cells with vacuolated cytoplasm were also observed. The metal exposed groups showed significant variation in the frequency of cellular abnormalities as well as the extent of DNA damage in comparison to controls. These frequencies increased significantly (p<0.05) in concentration dependent manner, peaking on 10th day while a decreasing trend was observed after 15 days of the exposure period.

The chromatin-binding protein HMGN3 stimulates histone acetylation and transcription across the Glyt1 gene.

HMGNs are nucleosome-binding proteins that alter the pattern of histone modifications and modulate the binding of linker histones to chromatin. The HMGN3 family member exists as two splice forms, HMGN3a which is full-length and HMGN3b which lacks the C-terminal RD (regulatory domain). In the present study, we have used the Glyt1 (glycine transporter 1) gene as a model system to investigate where HMGN proteins are bound across the locus in vivo, and to study how the two HMGN3 splice variants affect histone modifications and gene expression. We demonstrate that HMGN1, HMGN2, HMGN3a and HMGN3b are bound across the Glyt1 gene locus and surrounding regions, and are not enriched more highly at the promoter or putative enhancer. We conclude that the peaks of H3K4me3 (trimethylated Lys(4) of histone H3) and H3K9ac (acetylated Lys(9) of histone H3) at the active Glyt1a promoter do not play a major role in recruiting HMGN proteins. HMGN3a/b binding leads to increased H3K14 (Lys(14) of histone H3) acetylation and stimulates Glyt1a expression, but does not alter the levels of H3K4me3 or H3K9ac enrichment. Acetylation assays show that HMGN3a stimulates the ability of PCAF [p300/CREB (cAMP-response-element-binding protein)-binding protein-associated factor] to acetylate nucleosomal H3 in vitro, whereas HMGN3b does not. We propose a model where HMGN3a/b-stimulated H3K14 acetylation across the bodies of large genes such as Glyt1 can lead to more efficient transcription elongation and increased mRNA production.