Search Results (6)

Forskolin (FSK) is a potent adenylate cyclase activator and may display endocrine-disruptive effects via the disruption of steroidogenesis. Here, we tested this hypothesis by use of the in vitro H295R steroidogenesis assay and the in vivo long-term medaka (Oryzias latipes) exposure assay. The results from the H295R assay demonstrated that the transcriptional levels of a series of genes involved in steroidogenesis, including HSD3B2, CYP11A, CYP11B2, CYP17, CYP19, and CYP21, were remarkably up-regulated. Meanwhile, the productions of estrogens (17β-estradiol (17β-E₂) and estrone (E₁)) and progestins (progesterone (PGT) and 17-hydroxyprogesterone (17-HPT)) were significantly increased, and those of androgens (androstenedione (ADD) and testosterone (TTR)) were significantly inhibited. After waterborne exposure of medaka to FSK for 100 days, the gene expressions of HMGR, HSD17B1, CYP17B, CYP19A, and CYP21A were significantly enhanced in the gonads of male medaka. 17β-E2 was remarkably induced, although without statistical significance. In addition, the biomarker genes for estrogenicity, including VTG-I, VTG-II, CHG-H, and CHG-L, were significantly induced in male medaka livers. Pathological damage to their gonads was further identified. Therefore, the results demonstrated that FSK modulates the transcriptions of steroidogenesis genes and alters hormone levels in vitro and in vivo, which is a mark of endocrine disruption in organisms. Full article

The threat posed by water pollutants to aquatic ecosystems and human health cannot be overlooked, and the assessment of the toxicity of these contaminants is paramount to understanding their risks and formulating effective control measures. Luminescent bacteria-based assays, as a vital tool in evaluating contaminant toxicity, encounter a challenge in ensuring accuracy due to the phenomenon of “Hormesis” exhibited by pollutants towards biological entities, which may skew toxicity assessments. This study elucidated the specific effects of pollutants on luminescent bacteria at different concentrations, used modeling to characterize the effects and predict their toxicity trends, and explored the applicable concentration ranges for different pollutants. Research revealed that six typical pollutants, namely PAHs, endocrine disruptors, antibiotics, pesticides, heavy metals, and phytosensory substances, could promote the luminescence intensity of luminescent bacteria at low concentrations, and the promotional effect increased and then decreased. However, when the concentration of the substances reached a certain threshold, the effect changed from promotional to inhibitory, and the rate of inhibition was directly proportional to the concentration. The EC50 values of six types of substances to luminescent bacteria is as follows: endocrine disruptors > pesticides > antibiotics > heavy metals > polycyclic aromatic hydrocarbons > chemosensory agents. The effect curves were further fitted using the model to analyze the maximum point of the promotion of luminescence intensity by different substances, the threshold concentration, and the tolerance of luminescent bacteria to different substances. The maximum promotion of bacterial luminescence intensity was 29% for Bisphenol A at 0.005 mg/L and the minimum threshold concentration of chromium was 0.004 mg/L, and the maximum bacterial tolerance to erythromycin is 6.74. In addition, most of the current environmental concentrations had a positive effect on luminescent bacteria and may still be in the range of concentrations that promote luminescence as the substances continue to accumulate. These findings will enhance the accuracy and comprehensiveness of toxicity assessments, thereby facilitating more informed and effective decision-making in the realms of environmental protection and pollution management. Full article

This study explores the potential efficacy of chlorogenic acid (CGA) in mitigating lipopolysaccharide (LPS)-induced cystitis in a mice model. C57BL/6J mice were divided into four groups: normal control (NC), LPS, LPS + low CGA, and LPS + high CGA. Evaluation methods included cystometrogram (CMG), histopathological, western blot, and immunohistological analysis. In the LPS group, CMG revealed abnormal voiding behavior with increased micturition pressure, voided volume (VV), and decreased voided frequency. Low CGA treatment in LPS mice demonstrated improved micturition pressure and inter-contraction intervals (ICI). However, high CGA treatment exhibited prolonged ICI and increased VV, suggesting potential adverse effects. Histological analysis of LPS-treated mice displayed bladder inflammation and interstitial edema. Low CGA treatment reduced interstitial edema and bladder inflammation, confirmed by Masson’s trichrome staining. Western blotting revealed increased cytokeratin 20 (K20) expression in the low CGA group, indicating structural abnormalities in the bladder umbrella layer after LPS administration. In conclusion, low CGA treatment positively impacted voiding behavior and decreased bladder edema and inflammation in the LPS-induced cystitis mice model, suggesting its potential as a supplement for inflammation cystitis prevention. However, high CGA treatment exhibited adverse effects, emphasizing the importance of dosage considerations in therapeutic applications. Full article

The low-dose toxicity of chloride and nitrate salts of three lanthanides (La, Ce and Nd) was tested on six microfungal species. Five of them (Geomyces vinaceus, Aspergillus niveoglaucus, Pseudogymnoascus pannorum, Penicillium simplicissimum and Umbelopsis isabellina) were isolated from the loparite ore tailings on the Kola Peninsula, northwestern Russia. Sydowia polyspora was a control strain. In the case of nitrate salts, the toxicity of REEs to four of six microorganisms was significantly (p < 0.5) lower compared to chloride salts. In this case, nitrates can play the role of exogenous nutrients, compensating for the toxic effect of REEs. Interestingly, U. isabellina only showed an opposite response, indicating the highest toxicity of nitrate (IC₅ = 9–20 mg/L) REEs’ salts compared to chlorides (IC₅ = 80–195 mg/L) at low concentration levels. In addition, treatment with lanthanides showed a “hormesis effect” on fungal growth with stimulation at low doses and inhibition at high doses. However, U. isabellina and S. polyspora demonstrated the absence of hormetic response under the treatment of REEs’ nitrate salt. Taking into account the specific hormetic responses and high tolerance of P. simplicissimum and U. isabellina to lanthanides, our findings may be useful in the assessment of the potential application of the selected fungi to bioremediation and REE bioleaching. Full article

Objective: To investigate the role of miR-212-5p-targeted ARAF during the apoptosis of rat alveolar macrophages induced by cowshed PM_2.5. Methods: miRNA and related target genes and pathways were predicted using the KEGG, TargetScan, and other prediction websites. NR8383 macrophages were treated with cowshed PM_2.5 to establish an in vitro lung injury model in rats; meanwhile, for the assessment of cell viability, apoptosis, intracellular calcium ions, and mitochondrial membrane potential in NR8383 cells, RT-qPCR was used to detect the expression of miR-212-5p and the target gene ARAF. Results: The bioinformatic analyses showed that miR-212-5p and ARAF were involved in PM_2.5-associated cellular damage. Exposure to different concentrations (0 μg/mL, 60 μg/mL, 180 μg/mL, 300 μg/mL) with different durations (0 h, 12 h, 24 h, 48 h) of cowshed PM_2.5 resulted in apoptosis, increased intracellular calcium ions, and decreased mitochondrial membrane potential. The miR-212-5p mimic group showed an up-regulation of Bax and cleaved Caspase 3 expression but decreased Bcl2 expression compared to the NC group, and overexpression of ARAF up-regulated the expression of p-MEK1/2 and p-ERK1/2 and simultaneously reversed the above phenomena. Conclusions: miR-212-5p targets ARAF to affect the cowshed PM_2.5-induced apoptosis through the MEK/ERK signaling pathway, providing a potential target for relevant farming industry and pathology studies. Full article

A mathematical model for radiation hormesis below 100 mSv has previously been reported, but the origins of the formula used in the previous report were not provided. In the present paper, we first considered a sequential reaction model with identical rate constants. We showed that the function of components produced in the second step of this model agreed well with the previously reported function. Furthermore, in a general sequential reaction model with different rate constants, it was mathematically proved that the function representing the component produced in the second step is always mountain-shaped: the graph has a peak with one inflection point on either side, and such a component may induce radiation hormesis. Full article