Evidence for neurotoxicity and oxidative stress in zebrafish embryos/larvae treated with HFPO-DA ammonium salt (GenX).

"GenX" [ammonium perfluoro (2-methyl-3-oxahexanoate] was developed as a replacement chemical for toxic perfluorinated compounds to be used in product manufacturing. Here, we assessed developmental, mitochondrial, and behavioral toxicity endpoints in zebrafish embryos/larvae exposed to GenX. GenX exerted low toxicity to zebrafish embryos/larvae up to 20 mg/L. GenX did not affect mitochondrial oxidative phosphorylation nor ATP levels. ROS levels were reduced in larvae fish exposed to 10 and 100 µg/L, indicative of an antioxidant defense; however, ROS levels were elevated in fish exposed to 1000 µg/L. Increased expression of cox1 and sod2 in GenX exposed 7-day larvae was noted. GenX (0.1 or 1 µg/L) altered transcripts associated with neurotoxicity (elavl3, gfap, gap43, manf, and tubb). Locomotor activity of larvae was reduced by 100 µg/L GenX, but only in light periods. Perturbations of anxiety-related behaviors in larvae were not observed with GenX exposure. These data inform risk assessments for long-lived perfluorinated chemicals of concern.

Probiotic potentials of lactic acid bacteria isolated from Egyptian fermented food.

Lactic acid bacteria (LAB) are of major concern due to their health benefits. Fermented food products comprise variable LAB demonstrating probiotic properties. Discovering and evaluating new probiotics in fermented food products poses a global economic and health importance. Therefore, the present work aimed to investigate and evaluate the probiotic potentials of LAB strains isolated from Egyptian fermented food. In this study, we isolated and functionally characterized 100 bacterial strains isolated from different Egyptian fermented food sources as probiotics. Only four LAB strains amongst the isolated LAB showed probiotic attributes and are considered to be safe for their implementation as feed or dietary supplements. Additionally, they were shown to exert antimicrobial activities against pathogenic bacteria and anticancer effects against the colon cancer cell line Caco-2. The Enterococcus massiliensis IS06 strain was exclusively reported in this study as a probiotic strain with high antimicrobial, antioxidant, and anti-colon cancer activity. Hitherto, few studies have focused on elucidating the impact of probiotic supplementation in vivo. Therefore, in the current study, the safety of the four strains was tested in vivo through the supplementation of rats with potential probiotic strains for 21 days. The results revealed that probiotic bacterial supplementation in rats did not adversely affect the general health of rats. The Lactiplantibacillus plantarum IS07 strain significantly increased the growth performance of rats. Furthermore, the four strains exhibited increased levels of antioxidants such as superoxide dismutase and glutathione in vivo. Consistently, all strains also showed high antioxidant activity of the superoxide dismutase enzyme in vitro. Overall, these findings demonstrated that these isolated potential probiotics harbor desirable characteristics and can be applied widely as feed additives for animals or as dietary supplements for humans to exert their health benefits and combat serious diseases.

Association between cyclin-dependent kinase inhibitor 2B antisense RNA 1 and zinc finger homeobox 3 gene polymorphisms and COVID-19 severity.

BACKGROUND: There is no doubt about the cardiovascular complications of coronavirus disease 2019 (COVID-19). Several genetic studies have demonstrated an association between genetic variants in a region on chromosome 9p21 and in a region on chromosome 16q22 with myocardial infarction (MI) and atrial fibrillation (AF) accompanied by cerebral infarction (CI), respectively. OBJECTIVES: MI and CI susceptibility in patients with CDKN2B-AS1 and ZFHX3 polymorphisms, respectively, may have an effect on COVID-19 severity. We aimed to investigate whether there is an association between the cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) rs1333049 and zinc finger homeobox 3 (ZFHX3) rs2106261 single nucleotide polymorphisms (SNPs) and the degree of COVID-19 severity. SUBJECTS AND METHODS: This current work was carried out on 360 subjects. They were classified into three groups: 90 severe COVID-19 cases, 90 moderate COVID-19 cases and 180 age- and gender-matched healthy controls. All subjects underwent genotyping of CDKN2B-AS1 (rs1333049) and ZFHX3 (rs2106261) by real-time PCR. RESULTS: The frequency of G/C in CDKN2B-AS1 (rs1333049) was higher in severe and moderate COVID-19 patients than in controls (71.1% and 53.3% vs. 37.8%). The frequency of the C/C of CDKN2B-AS1 (rs1333049) was higher in moderate COVID-19 patients than in controls (26.7% vs. 13.3%). There were no significant differences regarding genotype frequency and allelic distribution of ZFHX3 (rs2106261) between COVID-19 patients and healthy controls. CONCLUSION: CDKN2B-AS1 (rs1333049) gene polymorphism may play a role in determining the degree of COVID-19 severity. Further studies on its effect on cyclins and cyclin-dependent kinases (CDKs) [not measured in our study] may shed light on new treatment options for COVID-19.

Hepatic demethylation of methoxy-bromodiphenyl ethers and conjugation of the resulting hydroxy-bromodiphenyl ethers in a marine fish, the red snapper, Lutjanus campechanus, and a freshwater fish, the channel catfish, Ictalurus punctatus.

Methoxylated bromodiphenyl ethers (MeO-BDEs), marine natural products, can be demethylated by cytochrome P450 to produce hydroxylated bromodiphenyl ethers (OH-BDEs), potentially toxic metabolites that are also formed by hydroxylation of BDE flame retardants. The OH-BDEs may be detoxified by glucuronidation and sulfonation. This study examined the demethylation of 6-MeO-BDE47, 2'-MeO-BDE68 and 4'-MeO-BDE68, in hepatic microsomes from the red snapper, Lutjanus campechanus, a marine fish likely to be exposed naturally to MeO-BDEs, and the channel catfish, Ictalurus punctatus, a freshwater fish in which pathways of xenobiotic biotransformation have been studied. We further studied the glucuronidation and sulfonation of the resulting OH-BDEs as well as of 6-OH-2'-MeO-BDE68 in hepatic microsomes and cytosol fractions of these fish. The three studied biotransformation pathways were active in both species, with high individual variability. The range of activities overlapped in the two species. Demethylation of MeO-BDEs, studied in the concentration range 10-500 µM, followed Michaelis-Menten kinetics in both fish species, however enzyme efficiencies were low, ranging from 0.024 to 0.334 µL min.mg protein. Conjugation of the studied OH-BDEs followed Michaelis-Menten kinetics in the concentration ranges 1-50 µM (glucuronidation) or 2.5-100 µM (sulfonation). These OH-BDEs were readily glucuronidated and sulfonated in the fish livers of both species, with enzyme efficiencies one to three orders of magnitude higher than for demethylation of the precursor MeO-BDEs. The relatively low efficiencies of demethylation of the MeO-BDEs, compared with higher efficiencies for OH-BDE conjugation, suggests that MeO-BDEs are more likely than OH-BDEs to bioaccumulate in tissues of exposed fish.