Synergistic effects of T-2 toxin and selenium deficiency exacerbate renal fibrosis through modulation of the ERα/PI3K/Akt signaling pathway.

As common pathogenic agents in the world and widely distributed globally, T-2 toxin and selenium deficiency might exacerbate toxic effects by combined exposure, posing a dramatic health hazard to humans and animals. In this study, we aim to elucidate the underlying mechanisms of renal fibrosis triggered by T-2 toxin and selenium deficiency exposure. A total of thirty-two rats are randomly divided into the normal control, T-2 toxin, selenium deficiency, and combined intervention groups. T-2 toxin (100 ng/g) is intragastric gavaged to the rats in compliance with the body weight. Both the standard (containing selenium 0.20 mg/Kg) and selenium-deficient (containing selenium 0.02 mg/Kg) diets were manufactured adhering to the AIN-93 formula. After 12 weeks of intervention, renal tissue ultrastructural and pathological changes, inflammatory infiltration, epithelial mesenchymal transition (EMT), and extracellular matrix (ECM) deposition are evaluated, respectively. Metabolomics analysis is conducted to explore the underlying pathology of renal fibrosis, followed by the validation of potential mechanisms at gene and protein levels. T-2 toxin and selenium deficiency exposure results in podocyte foot process elongation or fusion, tubular vacuolization and dilatation, and collagen deposition in the kidneys. Additionally, it also increases inflammatory infiltration, EMT conversion, and ECM deposition. Metabolomics analysis suggests that T-2 toxin and selenium deficiency influence amino acid and cholesterol metabolism, respectively, and the estrogen signaling pathway is probably engaged in renal fibrosis progression. Moreover, T-2 toxin and selenium deficiency are found to regulate the expressions of the ERα/PI3K/Akt signaling pathway. In conclusion, T-2 toxin and selenium deficiency synergistically exacerbate renal fibrosis through regulating the ERα/PI3K/Akt signaling pathway, and inflammatory infiltration, EMT and ECM deposition are involved in this process.

Single and Combined Effects of Short-Term Selenium Deficiency and T-2 Toxin-Induced Kidney Pathological Injury Through the MMPs/TIMPs System.

The single and combined effects of short-term selenium (Se) deficiency and T-2 toxin-induced kidney pathological injury through the MMPs/TIMPs system were investigated. Forty-eight rats were randomly divided into control, 10 ng/g T-2 toxin, 100 ng/g T-2 toxin, Se-deficient, 10 ng/g T-2 toxin and Se deficiency combined, and 100 ng/g T-2 toxin and Se deficiency combined groups for a 4-week intervention. The kidney Se concentration was measured to evaluate the construction of animal models of Se deficiency. Kidney tissues were analyzed by hematoxylin-eosin staining, Masson staining, and transmission electron microscope to observe the pathological changes, the severity of kidney fibrosis, and ultrastructural changes, respectively. Meanwhile, quantitative polymerase chain reaction and immunohistochemical staining were used to analyze the gene and protein expression levels of matrix metallopeptidase 2/3 (MMP2/3) and tissue inhibitor of metalloproteinase 1 (TIMP1). The results showed that short-term Se deficiency and T-2 toxin exposure can cause kidney injury through tubular degeneration and even lead to kidney fibrosis. And the combination of T-2 toxin and Se deficiency had a synergistic effect on the kidney. A dose-response effect of the T-2 toxin was also observed. At the gene and protein levels, the expression of MMP2/3 in the intervention group increased, while the expression of TIMP1 decreased compared with the control group. In conclusion, short-term Se deficiency and T-2 toxin exposure might lead to injury and even the development of fibrosis in the kidneys, and combined intervention can increase the severity with a dose-dependent trend. MMP2/3 and TIMP1 likely play a significant role in the development of kidney fibrosis.

Altered Expression of the Hedgehog Pathway Proteins BMP2, BMP4, SHH, and IHH Involved in Knee Cartilage Damage of Patients With Osteoarthritis and Kashin-Beck Disease.

OBJECTIVE: To investigate the expression of Hedgehog (HH) signaling pathway proteins in knee articular cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA) patients. METHODS: Knee articular cartilage samples were collected from normal (N), OA, and KBD adults (aged 38-60 years) and divided into 3 groups with 6 subjects in each group. The localization of the HH pathway proteins bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4), Sonic hedgehog (SHH), and Indian hedgehog (IHH) was observed with the microscope after immunohistochemical (IHC) staining. Positive staining cell rates of each proteins were compared. RESULTS: The strongest stainings of all proteins were observed in the middle zones of all 3 groups. The positive staining rates of BMP4 and IHH were significantly lower in the OA and KBD groups than those in the N group in all 3 zones. The positive staining rates of BMP2 and SHH tend to be lower in the OA and KBD groups than those in the N group in the deep zone, while higher in the OA and KBD groups than those in the N group in superficial and middle zones. CONCLUSIONS: Altered expression of the HH pathway proteins BMP2, BMP4, SHH, and IHH was found in OA and KBD articular cartilage. There seemed to be a compensatory effect between SHH and IHH in cartilage damage. Further studies on the pathogenesis of OA and KBD may be carried out from these aspects in the future.

Influencing factors of residents' environmental health literacy in Shaanxi province, China: a cross-sectional study.

BACKGROUND: This study comprehensively analyzed the basic conditions and influencing factors of the residents' environmental health literacy (EHL) level in Shaanxi Province, China in 2020, and provided a scientific basis for exploring new ideas and new methods to improve the EHL level of the whole people. METHODS: In the cross-sectional study with a multi-stage random sampling method, 1320 participants were recruited in 6 neighborhood committees (administrative villages) from the Shaanxi province of China between 15-69 years old. The Core Questions for Assessment of EHL of Chinese Citizens (Trial Implementation) was adopted to measure the EHL of the respondents. RESULTS: The survey showed the level of EHL of residents is 17.6% in Shaanxi in 2020. Among them, the basic concepts, basic knowledge, and basic skills classification literacy levels are 34.7%, 6.89%, and 37.95% respectively. The EHL ratio of rural residents is significantly lower than that of urban residents (12.38 vs. 29.02%). A noticeable difference was shown in various aspects and environmental health issues of EHL between urban and rural populations. CONCLUSIONS: Many factors are affecting the level of EHL. Education and science popularization of basic environmental and health knowledge in key areas and populations should be strengthened, and behavioral interventions should be carried out according to the characteristics of the population.

Progress of Signaling Pathways, Stress Pathways and Epigenetics in the Pathogenesis of Skeletal Fluorosis.

Fluorine is widely dispersed in nature and has multiple physiological functions. Although it is usually regarded as an essential trace element for humans, this view is not held universally. Moreover, chronic fluorosis, mainly characterized by skeletal fluorosis, can be induced by long-term excessive fluoride consumption. High concentrations of fluoride in the environment and drinking water are major causes, and patients with skeletal fluorosis mainly present with symptoms of osteosclerosis, osteochondrosis, osteoporosis, and degenerative changes in joint cartilage. Etiologies for skeletal fluorosis have been established, but the specific pathogenesis is inconclusive. Currently, active osteogenesis and accelerated bone turnover are considered critical processes in the progression of skeletal fluorosis. In recent years, researchers have conducted extensive studies in fields of signaling pathways (Wnt/ß-catenin, Notch, PI3K/Akt/mTOR, Hedgehog, parathyroid hormone, and insulin signaling pathways), stress pathways (oxidative stress and endoplasmic reticulum stress pathways), epigenetics (DNA methylation and non-coding RNAs), and their inter-regulation involved in the pathogenesis of skeletal fluorosis. In this review, we summarised and analyzed relevant findings to provide a basis for comprehensive understandings of the pathogenesis of skeletal fluorosis and hopefully propose more effective prevention and therapeutic strategies.

Effect of Low Nutrition and T-2 Toxin on C28/I2 Chondrocytes Cell Line and Chondroitin Sulfate-Modifying Sulfotransferases.

OBJECTIVE: To investigate the effects of low nutrition and trichothecenes-2 toxin (T-2) on human chondrocytes cell line C28/I2 and the gene expression levels of some chondroitin sulfate (CS)-modifying sulfotransferases. METHODS: The chondrocytes were divided into 4 intervention groups: (a) control group (Dulbecco's modified Eagle's medium/Nutrient Mixture F-12 [DMEM/F-12] with fetal bovine serum [FBS]), (b) low-nutrition group (DMEM/F-12 without FBS), (c) T-2 group (DMEM/F-12 with FBS plus 20 ng/mL T-2), and (d) combined group (DMEM/F-12 without FBS plus 20 ng/mL T-2). Twenty-four hours postintervention, ultrastructural changes in the chondrocytes were observed by transmission electron microscopy (TEM). Live cell staining and methyl thiazolyl tetrazolium (MTT) assay were performed to observe cell viability. The expression of CS-modifying sulfotransferases, including carbohydrate sulfotransferase 3, 12, 13, 15 (CHST-3, CHST-12, CHST-13, and CHST-15, respectively), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction (RT-qPCR) analysis. RESULTS: The cells in the T-2 group and combined group had significantly lower live cell counts and relative survival rates than the control group. TEM pictures revealed decreased electron density of mitochondria in the low-nutrition group. The T-2 group and combined group both caused mitochondrial swelling, damage, and reduction in mitochondrial number. RT-qPCR showed a trend of altered expression of CHST and increased expression of UST genes under low-nutrition, T-2 toxin and combined interventions. CONCLUSIONS: These results show early-stage Kashin-Beck disease chondrocyte pathophysiology, consisting of chondrocyte cell damage and compensatory upregulation of CHST and UST genes.