Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.

Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.

Nanoselenium Alleviates Cadmium-Induced Cerebral Injury via Regulating Cerebral Metal Transporters and Metal-Regulatory Transcription Factor 1.

Cadmium (Cd) is a hazardous environmental metal that poses a global public health concern due to its high toxic potential. Nanoselenium (Nano-Se) is a nanoform of elemental Se that is widely used to antagonize heavy metal toxicity owing to its high safety margin with low doses. However, the role of Nano-Se in relieving Cd-induced brain damage is unclear. For this study, Cd-exposure-induced cerebral damage was established by using a chicken model. Administration of Nano-Se with Cd significantly decreased the Cd-mediated elevation of cerebral ROS, MDA, and H2O2 levels as well as markedly increased the Cd-mediated reduced activities of antioxidant biomarkers (GPX, T-SOD, CAT, and T-AOC). Accordingly, co-treatment with Nano-Se significantly reduced Cd-mediated increased Cd accumulation and recovered the Cd-induced biometal imbalance, notably Se and Zn. Nano-Se downregulated the Cd-induced upregulation of ZIP8, ZIP10, ZNT3, ZNT5, and ZNT6 and upregulated the Cd-mediated decreased expressions of ATOX1 and XIAP. Nano-Se also increased the Cd-mediated decreased mRNA levels of MTF1 and its target genes MT1 and MT2. Surprisingly, co-treatment with Nano-Se regulated the Cd-induced increased total protein level of MTF1 by reducing its expression. Moreover, altered selenoproteins regulation was recovered after co-treatment with Nano-Se as evidenced by increased expression levels of antioxidant selenoproteins (GPx1-4 and SelW) and Se transport-related selenoproteins (SepP1 and SepP2). The histopathological evaluation and Nissl staining of the cerebral tissues also supported that Nano-Se markedly reduced the Cd-induced microstructural alterations and well preserved the normal histological architectures of the cerebral tissue. Overall, the results of this research reveal that Nano-Se may be beneficial in mitigating Cd-induced cerebral injury in the brains of chickens. This present study provides a basis for preclinical research for its usefulness as a potential therapeutic for the treatment of neurodegeneration in the heavy-metal-induced neurotoxicity.

Association between blood manganese levels and depressive symptoms among US adults: A nationally representative cross-sectional study.

BACKGROUND: Recent studies indicated that manganese (Mn) levels were inconsistently associated with the prevalence of depression. We aimed to evaluate whether blood Mn concentrations were associated with the risk of depression among US adults. METHODS: Using the NHANES 2011-2019 datasets, we conducted a cross-sectional study in 16,572 eligible participants with complete data on blood Mn concentrations and depression diagnosis. A weighted multivariable logistic model and restricted cubic spline model were applied to explore the association and dose-response relationship of blood Mn concentrations with depression risk in the total population and subgroups. RESULTS: In the total population, compared with the lowest reference group of blood Mn, participants in the second, third, and fourth quartile had an OR of 0.84 (95%CI: 0.66, 1.07), 0.93 (95%CI: 0.73, 1.19) and 0.91 (95%CI: 0.71, 1.15) for depression (ptrend = 0.640). In subgroup analyses, doubling of blood Mn concentrations was associated with a 0.83-fold (95%CI: 0.67, 1.02), 0.30 -fold (0.14, 0.65) decreased risk of depression in females and other ethnic groups, respectively. Significant modification effects of ethnicity on the association of blood Mn concentrations with depression risk were observed. LIMITATIONS: cross-sectional study design and self-reported depressive symptoms. CONCLUSIONS: Elevated blood Mn concentrations were associated with decreased depression risk in females and other specific subgroups. Mn supplementation could be a potential pathway for intervention and prevention of depression.

Effects of alkaline mineral complex water supplementation on growth performance, inflammatory response, and intestinal barrier function in weaned piglets.

The purpose of the present study was to investigate the effects of drinking water alkaline mineral complex (AMC) supplementation on growth performance, intestinal morphology, inflammatory response, immunity, antioxidant defense system, and barrier functions in weaned piglets. In a 15-d trial, 240 weaned piglets (9.35 ± 0.86 kg) at 28 d of age (large white × landrace × Duroc) were randomly divided into two groups: the control (Con) group and the AMC group. Drinking water AMC supplementation improved (P < 0.01) final body weight (BW) and average daily gain (ADG) in weaned piglets compared to the Con group. Importantly, AMC reduced (P < 0.01) the feed-to-gain (F:G) ratio. AMC water improved the physical health conditions of piglets under weaning stress, as reflected by the decreased (P < 0.05) hair score and conjunctival score. Moreover, there was no significant (P > 0.05) difference in relatively small intestinal length, organ (liver, spleen, and kidney) indices, or gastrointestinal pH value in weaned piglets between the two groups. Of note, AMC significantly promoted the microvilli numbers in the small intestine and effectively ameliorated the gut morphology damage induced by weaning stress, as evidenced by the increased (P < 0.05) villous height (VH) and ratio of VH to crypt depth. Additionally, AMC lessened the levels of lipopolysaccharide (LPS, P < 0.01) and the contents of IL1ß (P<0.05), and TNF-α (P<0.05) in the weaned piglet small intestine. Conversely, the gut immune barrier marker, secretory immunoglobulin A (sIgA) levels in serum and small intestine mucosa were elevated after AMC water treatment (P < 0.01). Furthermore, AMC elevated the antioxidant mRNA levels of (P < 0.05) SOD 1-2, (P < 0.01) CAT, and (P < 0.01) GPX 1-2 in the small intestine. Likewise, the mRNA levels of the small intestine tight junction factors Occludin (P < 0.01), ZO-1 (P < 0.05), Claudin 2 (P < 0.01), and Claudin 5 (P<0.01) in the AMC treatment group were notably higher than those in the Con group. In conclusion, drinking water AMC supplementation has an accelerative effect on growth performance by elevating gut health by improving intestinal morphology, the inflammatory response, the antioxidant defense system, and barrier function in weaned piglets.

The piglet suffers vital physiological, environmental, and social challenges when it is weaned from the sow that can predispose the piglet to subsequent diseases and other production losses, and these challenges are responsible for serious economic losses to the swine industry. Weaning stress induces intestinal injury, decreased immunity, and digestive system dysfunction, which then reduces feed intake and inhibits the growth performance of piglets. It is well known that alternatives to antibiotics for preventing weaning stress in weaned farm animals are sorely needed. The biologically beneficial effects of alkaline mineral water are widely reported. Alkaline mineral complex (AMC), as an immunomodulator, is considered to have antistress effects in the swine industry. In addition, treatment through drinking water is considered to be an efficient and low-cost feasible disease control strategy. Drinking water AMC supplementation is expected to exert health benefits in pigs; however, the responses of weaned piglets to water supplemented with AMC have not been fully explored. Thus, this study explored the effects of drinking water AMC supplementation on growth performance and gut health in weaned piglets. Our results showed that AMC water supplementation conspicuously enhanced the growth performance by improving the gut health.

Rational formulation engineering of fraxinellone utilizing 6-O-α-D-maltosyl-ß-cyclodextrin for enhanced oral bioavailability and hepatic fibrosis therapy.

Although Fraxinellone (Frax) isolated from Dictamnus albus L. possessed excellent anti-hepatic fibrosis activity, oral administration of Frax suffered from the inefficient therapeutic outcome in vivo due to negligible oral absorption. At present, the oral formulation of Frax is rarely exploited. For rational formulation design, we evaluated preabsorption risks of Frax and found that Frax was rather stable while poorly dissolved in the gastrointestinal tract (78.88 µg/mL), which predominantly limited its oral absorption. Further solubility test revealed the outstanding capacity of cyclodextrin derivatives (CDs) to solubilize Frax (6.8-12.8 mg/mL). This led us to study the inclusion complexes of Frax with a series of CDs and holistically explore their drug delivery performance. Characterization techniques involving 1H-NMR, FT-IR, DSC, PXRD, and molecular docking confirmed the most stable binding interactions when Frax complexed with 6-O-α-D-maltosyl-ß-cyclodextrin (G2-ß-CD-Frax). Notably, G2-ß-CD-Frax exhibited the highest solubilizing capacity, fast dissolution rate, and superior Caco-2 cell internalization with no obvious toxicity. Pharmacokinetic studies demonstrated markedly higher oral bioavailability of G2-ß-CD-Frax (5.8-fold that of free drug) than other Frax-CDs. Further, long-term administration of G2-ß-CD-Frax (5 mg/kg) efficiently inhibited CCl4-induced hepatic fibrosis in the mouse without inducing any toxicity. Our results will inspire the continued advancement of optimal oral Frax formulations for anti-fibrotic therapy.

[Research in technical regulations for production of pollution-free Chinese herbal medicines].

Aimed to solve the issues of pesticide residue, heavy metal contents and harmful elements in the productive process of Chinese herbal medicines, the research team built the technical regulations for production of pollution-free Chinese herbal medicines. This regulation included the environment of production area, the process of production, quality of products etc., which were the key steps controlled the quality of Chinese herbal medicines. The environment of production area was selected according to the ecological factors which were stipulated by Ecological Suitability Regionalization of Chinese herbal medicines (second edition). The quality of air should be attain the one or two levels of GB/T3095-2012 standard values. The cultivation soils should reach to the one or two levels of GB15618 and NY/T391 standard values. The quality of irrigation water should accord with the stipulation of GB5084-2005. Aimed to the production of Chinese herbal medicines, disease-resistant and superior varieties which were suitable to the local stations should be selected, and the breeding of superior seeds and seedlings should be strengthened. Additionally, rational fertilizer application of pollution-free Chinese herbal medicines should be conformed to the principles, requirements, and the kinds of fertilizers allowed or limited for use, which were stipulated by the standard of DB13/T454. Furthermore, the plant protection policy of priority to prevention and synthetical prevention should be followed; improving ecological environment and strengthening cultivation management should be served as the basics. Agricultural measures, and biological and physical control strategies should be preferred to use; and high toxicity, residue pesticide and its mixture should be inhibited; the use of chemical pesticides should be minimized and then to decrease contamination and residue. Additionally, the quality of products should be reached to the standard of pollution-free Chinese herbal medicines; high toxicity and detection rate of pesticide residues and the contents of heavy metal and harmful elements (e.g. plumbum, cadmium, mercury, arsenic and cuprum) should accord with the common criteria of pollution-free Chinese herbal medicines. Application of technical regulations for production of pollution-free Chinese herbal medicines guarantees significantly social, economic and ecological benefits.

A new resveratrol trimer from the roots and stems of Vitis wenchowensis.

Phytochemical constituents of Vitis wenchowensis were investigated for the first time. A new resveratrol trimer, wenchowenol (1), was isolated from the roots and stems of Vitis wenchowensis along with four known stilbenoids 2-5. The structure and relative configuration of 1 were established on the basis of spectral evidence, especially HMBC and NOESY experiments. It showed potent antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radical.