Preliminary investigation into the impact of BPA on osteoblast activity and bone development: In vitro and in vivo models.

Bisphenol A (BPA), an ingredient in consumer products, has been suggested that it can interfere with bone development and maintenance, whereas the molecule mechanism remains unclear. The objective of this study is to investigate the effect of BPA on early bone differentiation and metabolism, and its potential molecule mechanism by employing hFOB1.19 cell as an in vitro model, as well as larval zebrafish as an in vivo model. The in vitro experiments indicated that BPA decreased cell viability, inhibited osteogenic activity (such as ALP, RUNX2), increased ROS production, upregulated transcriptional or protein levels of apoptosis-related molecules (such as Caspase 3, Caspase 9), while suppressed transcriptional or protein levels of pyroptosis-specific markers (TNF-α, TNF-ß, IL-1ß, ASC, Caspase 1, and GSDMD). Moreover, the evidences from in vivo model demonstrated that exposure to BPA distinctly disrupted pharyngeal cartilage, craniofacial bone development, and retarded bone mineralization. The transcriptional level of bone development-related genes (bmp2, dlx2a, runx2, and sp7), apoptosis-related genes (bcl2), and pyroptosis-related genes (cas1, nlrp3) were significantly altered after treating with BPA in zebrafish larvae. In summary, our study, combining in vitro and in vivo models, confirmed that BPA has detrimental effects on osteoblast activity and bone development. These effects may be due to the promotion of apoptosis, the initiation of oxidative stress, and the inhibition of pyroptosis.

Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity.

Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe2+ content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe2+ metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.

Behavioral changes and transcriptomic effects at embryonic and post-embryonic stages reveal the toxic effects of 2,2',4,4'-tetrabromodiphenyl ether on neurodevelopment in zebrafish (Danio rerio).

Polybrominated biphenyl ethers (PBDEs) are new persistent pollutants that are widely exist in the environment and have many toxic effects. However, their toxicity mechanisms on neurodevelopment are still unclear. In this study, zebrafish embryos were exposed to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) (control, 10, 50 and 100 µg/L) at 2 h postfertilization (hpf) - 7 dpf. Locomotion analysis indicated that BDE-47 increased spontaneous coiling activity in zebrafish embryos under high-intensity light stimuli and decreased locomotor in zebrafish larvae. RNA-Seq analysis revealed that most of the up-regulated pathways were related to the metabolism of cells and tissues, while the down-regulated pathways were related to neurodevelopment. Consistent with the locomotion and KEGG results, BDE-47 affected the expression of genes for central nervous system (gfap, mbpa, bdnf & pomcb), early neurogenesis (neurog1 & elavl3), and axonal development (tuba1a, tuba1b, tuba1c, syn2a, gap43 & shha). Furthermore, BDE-47 interfered with gene expression of the Wnt signaling pathway, especially during embryonic stages, suggesting that the mechanisms of BDE-47 toxicity to zebrafish at various stages of neurodevelopment may be different. In summary, early neurodevelopment effects and metabolic disturbances may have contributed to the abnormal neurobehavioral changes induced by BDE-47 in zebrafish embryos/larvae, suggesting the neurodevelopmental toxicity of BDE-47.

Effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on reproductive and endocrine function in female zebrafish (Danio rerio).

BACKGROUND: Polybrominated diphenyl ethers (PBDEs), a group of brominated flame retardants (BFRs), were reported exist extensively in various ecological environmental. Studies have indicated that PBDEs induce reproductive toxic effects on human health, but the mechanisms remain poorly understood. In this study, the adult female zebrafish were used to investigate the effects of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) on the reproductive endocrine system and its mechanism. METHODS: Female zebrafish (AB strains) were continuously exposed to BDE-47 at the concentrations of 0, 10, 50, 100 and 500 µg/L till 21 days. The morphology of ovary were stained and evaluated with hematoxylin-eosin (H&E), and levels of sex hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and 17ß-estradiol (E2) and the biomarkers of oxidative stress such as superoxide dismutase (SOD) and malondialdehyde (MDA), were measured via ELISA. Subsequently, the expression of genes along the hypothalamic pituitary-gonad (HPG) and oxidative stress were determined using quantitative real-time PCR (qRT-PCR). RESULT: The results showed that exposure to high level of BDE-47 reduced the index of condition factor (CF) and gonadosomatic index (GSI). Treatment with BDE-47 impaired the normal development and structure of oocytes in zebrafish ovary. Moreover, the steroid hormone of FSH, LH, T and E2 were significantly decreased in BDE-47 exposure group. A dose-dependent elevation in SOD activity and MDA levels were recorded. Meanwhile, the transcription level of cyp19a, cyp19b, fshß, lhß were up-regulated while the transcription of fshr, lhr, cyp17a, 17ßhsd were down-regulated in the gonad of female adult zebrafish. CONCLUSION: Exposure to BDE-47 have detrimental impact on the development of ovary, decreasing sex hormone levels, inducing oxidative damage as well as altering HPG axis-related genes.

Associations between polybrominated diphenyl ethers (PBDEs) levels in adipose tissues and blood lipids in women of Shantou, China.

Animal studies have indicated that exposure to polybrominated diphenyl ethers (PBDEs) during development can permanently affect blood/liver lipid balance. However, no epidemiological study has assessed the relationship between PBDEs in adipose tissues and blood lipid metabolism. In this study, we explored the associations between PBDEs levels in female adipose tissues and lipid profiles. We recruited 150 female patients undergoing plastic surgery from hospital in Shantou, China, collected their characteristics, clinical information, and adipose tissue samples. Fourteen PBDE congeners in adipose tissues were analyzed by gas chromatography-mass spectrometry (GC-MS). Multiple linear and logistic regression models were used to explore the relationships between PBDEs and lipid profiles, while restricted cubic spline (RCS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the nonlinearity of mixtures. Median levels of ΣPBDEs and dominant congeners BDE-153, -209, and -183 in adipose tissues were 73.91, 26.12, 14.10 and 9.01 ng/g lipid, respectively. In the multiple linear model, BDE-153 and BDE-209 were negatively associated with triglycerides (TG), similarly for BDE-190 and total cholesterol (TC). While in the adjusted logistic models, BDE-138 was negatively associated with TC (OR = 0.76, 95%CI: 0.58, 0.99) and total lipids (TL) (OR = 0.76, 95%CI: 0.58, 0.99). Diastolic blood pressure was positively correlated with BDE-28 and BDE-71 (P < 0.05). Furthermore, a non-linear relationship was observed in BDE-138 and blood lipid levels using a RCS model (Pnonlinearity<0.05). BKMR analysis indicated that with the cumulative levels across PBDEs increased, the health risks of hypertriglyceridemia gradually rebounded, and the health risks of hypercholesterolemia and high total lipid gradually rebounded and then declined, but without statistical significance. PBDEs pollution was still prevalent in Shantou city, and several PBDE congeners were significant risk factors for dyslipidemia and blood pressure alteration. There exist deleterious effects of PBDEs and blood lipids.

CuO-NPs-triggered heterophil extracellular traps exacerbate liver injury in chicks by promoting oxidative stress and inflammatory responses.

With the widespread use of copper oxide nanoparticles (CuO-NPs), their potential toxicity to the environment and biological health has attracted close attention. Heterophil extracellular traps (HETs) are an innate immune mechanism of chicken heterophils against adverse stimuli, but excessive HETs cause damage. Here, we explored the effect and mechanism of CuO-NPs on HETs formation in vitro and further evaluated the potential role of HETs in chicken liver and kidney injury. Heterophils were exposed to 5, 10, and 20 µg/mL of CuO-NPs for 2 h. The results showed that CuO-NPs induced typical HETs formation, which was dependent on NADPH oxidase, P38 and extracellular regulated protein kinases (ERK1/2) pathways, and glycolysis. In in vivo experiments, fluorescence microplate and morphological analysis showed that CuO-NPs elevated the level of HETs in chicken serum and caused liver and kidney damage. Meanwhile, CuO-NPs caused hepatic oxidative stress (MDA, SOD, CAT, and GSH-PX imbalance), and also induced an increase in mRNA expression of their inflammatory and apoptosis-related factors (IL-1ß, IL-6, TNF-α, COX-2, iNOS, NLRP3, and Caspase-1, 3, 11). However, these results were significantly altered by DNase I (HETs degradation reagent). In conclusion, the present study demonstrates for the first time that CuO-NPs induce the formation of HETs and that HETs exacerbate pathological damage in chicken liver and kidney by promoting oxidative stress and inflammation, providing insights into immunotoxicity and potential prevention and treatment targets caused by CuO-NPs overexposure.

Quantitative and amplification-free detection of SOCS-1 CpG methylation percentage analyses in gastric cancer by fiber optic nanoplasmonic biosensor.

A new innovative approach is essential for early and effective diagnosis of gastric cancer, using promoter hypermethylation of the tumor suppressor, SOCS-1, that is frequently inactivated in human cancers. We have developed an amplification-free fiber optic nanoplasmonic biosensor for detecting DNA methylation of the SOCS-1 human genome. The method is based on the fiber optic nanogold-linked sorbent assay of PCR-free DNA from human gastric tumor tissue and cell lines. We designed a specific DNA probe fabricated on the fiber core surface while the other probe is bioconjugated with gold nanoparticles in free form to allow percentage determination and differentiating the methylated and unmethylated cell lines, further demonstrating the SOCS-1 methylation occurs in cancer patients but not in normal cell lines. The observed detection limit is 0.81 fM for methylated DNA, and the detection time is within 15 min. In addition, our data were significantly correlated to the data obtained from PCR-based pyrosequencing, and yet with superior accuracy. Hence our results provide new insight to the quantitative evaluation of methylation status of the human genome and can act as an alternative to PCR with a great potential.

Facile and Selective Determination of Total Phthalic Acid Esters Level in Soft Drinks by Molecular Fluorescence Based on Petroleum Ether Microextraction and Selective Derivation by H2SO4.

Determining the level of phthalic acid esters (PAEs) in packaged carbonated beverages is a current need to ensure food safety. High-selectivity and -accuracy identification of individual PAEs can be achieved by chromatographic and mass spectrometric (MS) techniques. However, these methods are slow; involve complicated, expensive instruments in professional laboratories; and consume a large amount of organic solvents. As such, a food analysis method is needed to conveniently and rapidly evaluate multiple contaminants on site. In this study, with the assistance of ultrasound, we quickly determined the total PAEs in soft drinks using 1.5 mL of petroleum ether in one step. Then, we determined the characteristic molecular fluorescence spectrum of all PAEs in samples (excitation (Ex)/emission (Em) at 218/351 nm) using selectively concentrated sulfuric acid derivatization. The relative standard deviations of the fluorescent intensities of mixed solutions with five different PAEs were lower than 7.1% at three concentration levels. The limit of detection of the proposed method is 0.10 µmol L-1, which matches that of some of the chromatographic methods, but the proposed method uses less organic solvent and cheaper instruments. These microextraction devices and the fluorescence spectrometer are portable and provide an instant result, which shows promise for the evaluation of the total level of PAEs in beverages on site. The proposed method successfully detected the total level of PAEs in 38 kinds of soft drink samples from local supermarkets, indicating its potential for applications in the packaged beverage industry.

A closed-circuit cycle process for recovery of carbon and valuable components from spent carbon cathode by hydrothermal acid-leaching method.

Spent carbon cathode (SCC) as a hazardous solid waste produced in aluminum electrolysis industry, contains plenty valuable components but generate a seriously threat to the environment. This paper focus on a closed-circuit cycle process for direct treatment of SCC based on the hydrothermal acid-leaching method. Thermodynamic calculation, single factor experiment, orthogonal experiment and kinetic study are utilized to obtain the leaching properties of impurities, optimize the leaching conditions, study the influence of conditions on leaching, and capture the restriction factors of leaching. The results indicate that the carbon content of the treated SCC can reach 97.3% when the leaching condition attach the optimal (liquid-solid ratio of 25 mL/g, temperature of 413 K, time of 270 min and acid concentration of 4 mol/L), and liquid-solid ratio is regarded as the crucial factor influencing on that. In addition, the activation energy of impurities reaches 6.25 kJ/mol and the whole leaching process is controlled by the diffusion extent. Finally, the filtrate after the hydrothermal acid leaching is treated, and calcium fluoride, cryolite and sodium chloride are successfully separated. The proposed process eliminates the harm of SCC to the environment, and completes a closed-circuit cycle for the treatment of SCC and recovery of valuable components. It enriches the hydrometallurgical processes of SCC, and provides an attractive scheme for the treatment of SCC.

Exploration of novel phthalazinone derivatives as potential efflux transporter inhibitors for reversing multidrug resistance and improving the oral absorption of paclitaxel.

Chemotherapy is an important means of cancer treatment. However, overexpression of efflux transporters (including but not limited to P-gp and BCRP) can lead to resistance to cancer chemotherapy. Multiple-target inhibitors of efflux transporter can be overcome the resistance and improve the oral bioavailability of chemotherapy drugs. Therefore, we designed and synthesized a series of phthalazinone ring derivatives (1-20) with different aromatic heterocycles substituents on the amide bond for dual inhibition of P-gp and BCRP. Most target compounds significantly increased the accumulation of P-gp substrates in the chemo-resistant cancer cell lines by inhibiting the efflux of transporters. Compound 19 in particular showed stronger MDR reversal compared to Gefitinib and Verapamil, and comparable to that of the BCRP inhibitor Ko143. In addition, compound 19 improved intestinal absorption of paclitaxel (PTX) and enhanced the bioavailability of the orally administered drug in vivo.

PCDHB15 as a potential tumor suppressor and epigenetic biomarker for breast cancer.

Breast cancer is among the most frequently diagnosed cancer types and the leading cause of cancer-related death in women. The mortality rate of patients with breast cancer is currently increasing, perhaps due to a lack of early screening tools. In the present study, using The Cancer Genome Atlas (TCGA) breast cancer dataset (n=883), it was determined that methylation of the protocadherin ß15 (PCDHB15) promoter was higher in breast cancer samples than that in normal tissues. A negative association between promoter methylation and expression of PCDHB15 was observed in the TCGA dataset and breast cancer cell lines. In TCGA cohort, lower PCDHB15 expression was associated with shorter relapse-free survival times. Treatment with the DNA methyltransferase inhibitor restored PCDHB15 expression in a breast cancer cell line; however, overexpression of PCDHB15 was shown to suppress colony formation. PCDHB15 methylation detected in circulating cell-free DNA (cfDNA) isolated from serum samples was higher in patients with breast cancer (40.8%) compared with that in patients with benign tumors (22.4%). PCDHB15 methylation was not correlated with any clinical parameters. Taken together, PCDHB15 is a potential tumor suppressor in cases of breast cancer, which can be epigenetically silenced via promoter methylation. PCDHB15 methylation using cfDNA is a novel minimally invasive epigenetic biomarker for the diagnosis and prognosis of breast cancer.

Structure-based discovery of receptor tyrosine kinase AXL degraders with excellent anti-tumor activity by selectively degrading AXL and inducing methuosis.

The receptor tyrosine kinase (RTK) anexelekto (AXL) is mutated and/or overexpressed in various malignancies, and plays a central role in tumor development and acquired drug resistance. Although highly selective inhibitors have been developed in recent years, direct inhibition of AXL may block its ubiquitination, eventually leading to surface accumulation of the protein. Herein, we designed and synthesized a series of AXL degraders with high selectivity and without compensatory increase of AXL. In particular, compounds 20 and 22 showed significant AXL degradation capacity, which inhibited the proliferation and migration of cancer cells in vitro. In addition, these compounds induced the formation of cytoplasmic vacuoles and triggered methuosis, a new type of non-apoptotic cell death, by stimulating excessive production of macropinosomes. Vacuole formation was mediated via H-Ras activation, and was attenuated upon inhibition of its downstream regulatory factor Rac1. Furthermore, compound 20 inhibited the growth of tumor cell xenografts in vivo, and prolonged the survival of the tumor-bearing mice.

The Mechanism and Prognostic Value of DNA Polymerase δ Subunits in Hepatocellular Carcinoma: Implications for Precision Therapy.

PURPOSE: Polymerase δ (POLD) proteins is a pivotal B-family DNA polymerase in the process of genome replication and repair and are comprised of POLD1-4. The predictive value of POLDs in hepatocellular carcinoma (HCC) has not been evaluated until now. PATIENTS AND METHODS: A total of 369 hepatocellular carcinoma samples and 50 adjacent normal samples were enrolled from the TCGA-LIHC database, and the GSE10186 database was also used. Transcription, methylation and genetic alteration status of HCC patients were evaluated by GEPIA, Kaplan-Meier plotter, cBioPortal, MethHC, MethSurv. SurvExpress was employed to generate the overall prognosis prediction signature of POLDs. POLDs coexpressed genes were explored and enriched in potential pathways. K-M curves were generated to compare the different survival results in different groups, while ROC curves were used to validate the efficiency of the POLD signature. RESULTS: All four POLD subunits were highly expressed in HCC tumor tissues. POLD1-3 and increased mRNA levels were also positively associated with advanced tumor stage and OS prognosis. Methylation in the promoter of POLDs affects mRNA expression and OS, especially for some specific CpG sites. Meanwhile, POLDs could preferably predict the prognosis for patients who suffered from a high gene mutation burden. We evaluated the combined prognostic predictive value of four POLD subunits in both the TCGA-LIHC and GSE10186 databases and recognized the statistically significant HR of the high-risk group, along with the reliable predictive value. The coexpressed gene sets and annotation results showed that the POLD coexpressed genes were mostly associated with DNA repair and cell cycle regulation pathways. CONCLUSION: POLD is an essential predictive factor for the prognosis of HCC. The united signature could precisely identify unfavorable clinical outcome of HCC.

Alumina nanoparticles-induced heterophil extracellular traps exacerbate liver injury by regulating oxidative stress and inflammation in chickens.

Widely used alumina nanoparticles (Al2O3 NPs) exposed to the environment pose a serious threat to human and animal health. The formation of heterophil extracellular traps (HETs) is a mechanism of innate immune defense against infection, but excessive HETs cause pathological damage. Here, we aim to explore the influence and mechanism of Al2O3 NPs on the formation of HETs in vitro, and further investigate the role of HETs release in histopathological damage after Al2O3 NPs treatment. Immunofluorescence analysis showed that Al2O3 NPs induced the formation of HETs, which was characterized by modified histones and elastase in the DNA backbone. Fluorescence microplate analysis showed that HETs formation was dependent on NADPH oxidase, P38, extracellular regulated protein kinases (ERK1/2) pathways and glycolysis. In vivo investigation showed that Al2O3 NPs significantly caused HETs release and liver damage. Biochemical analysis showed that Al2O3 NPs inhibited the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). Real-time fluorescence quantification results showed that Al2O3 NPs caused the overexpression of inflammation-related molecules interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), caspase-1 and caspase-11. All these changes were significantly changed by DNase I (Degradation reagent for HETs). Together, these suggest that Al2O3 NPs-induced HETs exacerbate liver injury by regulating oxidative stress and inflammatory responses, which provide a new perspective and potential prophylaxis and treatment targets for Al2O3 NPs toxicological research.

A designed cyclic peptide based on Trastuzumab used to construct peptide-drug conjugates for its HER2-targeting ability.

Human epidermal growth factor receptor 2 (HER2) has been recognized as an important therapeutic target for its overexpression in many cancers. Trastuzumab is a monoclonal antibody targeting HER2, which has been approved by FDA to treat HER2-positive cancer. In this research, cyclic peptide Cyclo-GCGPep1 was designed based on the binding mode between antibody and HER2 protein in silico, which has been confirmed possessing good affinity with HER2. Cyclo-GCGPep1 was also used to construct peptide-drug conjugates with Camptothecin. Biological evaluations demonstrated that Conjugate 1 has a good antiproliferative activity on SK-BR-3 and NCI-N87 cells. Conjugate 1 retained the pro-apoptotic and Topo I inhibitory ability of Camptothecin. Meanwhile, it has good targeting ability towards HER2-positive cells with the help of Cyclo-GCGPep1. It also has better permeability in the tumor spheroid model than Camptothecin. In summary, the design of cyclic peptide derived from antibody is of significance for the discovery of targeting peptides and Conjugate 1 is expected as a good therapeutic agent for HER2-positive cancers.

Morin alleviates aflatoxin B1-induced liver and kidney injury by inhibiting heterophil extracellular traps release, oxidative stress and inflammatory responses in chicks.

Aflatoxin B1 (AFB1) is a secondary metabolite produced by Aspergillus flavus and parasitic aspergillus, mainly existing in cereals, peanuts, corn, and other crops, which seriously endanger poultry, human health, and environment. Morin, a flavonoid compound extracted from moraceae plants, possess antioxidant, antibacterial, and anti-inflammatory effects. However, whether morin has a protective effect on AFB1-induced liver and kidney damage in chicks has not been specifically reported. In this study, we mainly confirmed the protective effect of morin on AFB1-induced liver and kidney damage in chicks and clarified its mechanism. It was found that morin can significantly reduce the liver biochemical indicators of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and kidney indicators of creatinine (CRE) and urea nitrogen (BUN) levels. Meanwhile, histopathological examination showed that morin effectively relieved AFB1-caused liver damage, including hepatocyte disruption, swelling, and inflammatory cell infiltration, and effectively relieved kidney damage, including renal cell necrosis, exfoliation, and vacuolization. Further investigation of its mechanism demonstrated that morin significantly inhibited AFB1-induced heterophil extracellular traps (HETs) release, and decreased the level of malondialdehyde (MDA) but increased the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in vivo. Moreover, quantitative real-time PCR (qRT-PCR) analysis showed that morin also significantly decreased AFB1-induced mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), caspase-1, caspase-3, and caspase-11. In conclusion, all results confirmed that morin could protect AFB1-caused liver and kidney damage by inhibiting HETs release, regulating oxidative stress, and inhibiting inflammatory response, suggesting that morin can be utilized as a potential drug for prevention and treatment of aflatoxicosis in poultry breeding industry.

Cyanidin-3-O-Glucoside improves the viability of human islet cells treated with amylin or Aß1-42 in vitro.

Islet transplantation is being considered as an alternative treatment for type 1 diabetes. Despite recent progress, transplant recipients continue to experience progressive loss of insulin independence. Cyanidin-3-O-Glucoside (C3G) has shown to be protective against damage that may lead to post-transplant islet loss. In this study, human islets cultured with or without C3G were treated with human amylin, Aß1-42, H2O2, or rapamycin to mimic stresses encountered in the post-transplant environment. Samples of these islets were collected and assayed to determine C3G's effect on cell viability and function, reactive oxygen species (ROS), oxidative stress, amyloid formation, and the presence of inflammatory as well as autophagic markers. C3G treatment of human islets exposed to either amylin or Aß1-42 increased cell viability (p<0.01) and inhibited amyloid formation (p<0.01). A reduction in ROS and an increase in HO-1 gene expression as well as in vitro islet function were also observed in C3G-treated islets exposed to amylin or Aß1-42, although not significantly. Additionally, treatment with C3G resulted in a significant reduction in the protein expression of inflammatory markers IL-1ß and NLRP3 (p<0.01) as well as an increase in LC3 autophagic marker (p<0.05) in human islets treated with amylin, Aß1-42, rapamycin, or H2O2. Thus, C3G appears to have a multi-faceted protective effect on human islets in vitro, possibly through its anti-oxidant property and alteration of inflammatory as well as autophagic pathways.

Baicalin protects against zearalenone-induced chicks liver and kidney injury by inhibiting expression of oxidative stress, inflammatory cytokines and caspase signaling pathway.

Zearalenone (ZEA) is a secondary metabolite produced by fungi such as Fusarium and Fusarium flavum, which is classified as a mycotoxin. Crops and feed in a humid surrounding are widely polluted by ZEA, which further endangering the healthful aquaculture of poultry and even human health. Up to now, prevention and cure of mycotoxicosis is still a crucial subject of poultry husbandry. Baicalin (BAI) is a flavonoid refined from dried roots of Scutellaria baicalensis possessing the function of hepatoprotective, anti-inflammatory, anti-oxidant, and anti-atherosclerotic efficacies.etc. But whether Baicalin also has a protective effect against ZEA intoxication is unclear. Therefore, the aim of this study was to establish a model of ZEA-induced toxic injury in chicks, and then to investigate the way in which Baicalin plays a protective role in the mechanism of ZEA-induced liver and kidney injury in chicks. The results exhibit that Baicalin could not only significantly decrease aspartate aminotransferase (AST) , alanine aminotransferase (ALT) and creatinine (Cre) levels in serum, but also ameliorate ZEA-induced pathologic changes of liver and kidney. Baicalin could also significantly regulate ZEA-induced the changes of catalase (CAT) , malondialdehyde (MDA) , total sulfhydryl group , except for glutathione peroxidase (GSH-px) , and inhibit the mRNA levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) , interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) with caspase-3 and caspase-11 in the caspase signaling pathway , meanwhile inhibit the cell apoptosis in immunohistochemistry. In summary, we successfully established a model of ZEA-induced liver injury in chicks, and confirm that Baicalin can reduce ZEA-induced liver and kidney injury in chicks. The mechanism of these effects is via inhibiting inflammation, oxidative stress and apoptosis, which also indicates the potential applicability of Baicalin for the prevention and treatment of ZEA-induced toxicity in chicks.

The effect of a high-quality nursing model employing low-frequency pulse electrical stimulation combined with early systemic functional exercises on the function of the affected limb in brachial plexus injury patients.

OBJECTIVE: To explore the effect of a high-quality nursing model employing low-frequency pulse electrical stimulation combined with early systemic functional exercises on the function of the affected limb in brachial plexus injury patients. METHODS: A total of 98 brachial plexus injury patients admitted to our hospital were recruited as the research cohort. All the patients were treated with surgery to repair, release, and transfer or transplant nerves according to each patient's condition. After the operations, the patients were randomly divided into one of two groups: the control group (n=49) or the research group (n=49). The control group did early systemic functional exercises, while the research group was administered low frequency pulse electrical stimulation in addition to doing the early systemic functional exercises. The clinical efficacy, the visual analogue scale (VAS) scores before and after the treatment, the brachial plexus function scores, the nerve conduction velocities and amplitudes, the SF-36 questionnaires, the incidences of complications, and the nursing satisfaction were compared between the two groups. RESULTS: After the treatment, the overall response rate to the treatment in the research group was significantly higher than it was in the control group (95.92% vs 81.63%, P<0.05). The VAS scores in both groups were decreased, and the scores in the research group were lower than the scores in the control group (P<0.05). The upper limb, lower limb, and the whole brachial plexus scores were increased in both groups, and the scores in the research group were higher than the scores in the control group (P<0.05). The motor conduction velocities, the sensory conduction velocities, and the amplitudes of the ulnar and median nerves in the two groups were increased, and the research group had higher levels than the control group (P<0.05). The emotional function, physical pain, physical health, role function, social function, mental health, energy, and general health scores in the two groups were increased, and the research group was higher than the control group (P<0.05). The incidence of complications in the research group was lower than it was in the control group, but the nursing satisfaction was higher than it was in the control group (all P<0.05). CONCLUSION: The high-quality nursing model based on low-frequency pulse electrical stimulation combined with early systemic functional exercise can effectively promote the functional recovery of the affected limb in brachial plexus injury patients. It can reduce pain and the incidence of complications and it can improve the quality of life and the satisfaction with the nursing at the same time.