Protective effects of dietary additive quercetin: Nephrotoxicity and ferroptosis induced by avermectin pesticide.

In recent years, contamination of aquatic systems with Avermectin (AVM) has emerged as a significant concern. This contamination poses substantial challenges to freshwater aquaculture. Plant-derived Quercetin (QUE), known for its anti-inflammatory, antioxidant, and ferroptosis-inhibiting properties, is commonly employed as a supplement in animal feed. However, its protective role against chronic renal injury in freshwater carp induced by AVM remains unclear. This study assesses the influence of dietary supplementation with QUE on the consequences of chronic AVM exposure on carp renal function. The carp were subjected to a 30-day exposure to AVM and were provided with a diet containing 400 mg/kg of QUE. Pathological observations indicated that QUE alleviated renal tissue structural damage caused by AVM. RT-QPCR study revealed that QUE effectively reduced the increased expression levels of pro-inflammatory factors mRNA produced by AVM exposure, by concurrently raising the mRNA expression level of the anti-inflammatory factor. Quantitative analysis using DHE tests and biochemical analysis demonstrated that QUE effectively reduced the buildup of ROS in the renal tissues of carp, activity of antioxidant enzymes CAT, SOD, and GSH-px, which were inhibited by AVM, and increased the content of GSH, which was induced by prolonged exposure to AVM. QUE also reduced the levels of MDA, a marker of oxidative damage. Furthermore, assays for ferroptosis markers indicated that QUE increased the mRNA expression levels of gpx4 and slc7a11, which were reduced due to AVM induction, and it caused a reduction in the mRNA expression levels of ftl, ncoa4, and cox2, along with a drop in the Fe2+ concentration. In summary, QUE mitigates chronic AVM exposure-induced renal inflammation in carp by inhibiting the transcription of pro-inflammatory cytokines. By blocking ROS accumulation, renal redox homeostasis is restored, thereby inhibiting renal inflammation and ferroptosis. This provides a theoretical basis for the development of freshwater carp feed formula.

Silybin prevented avermectin-induced cardiotoxicity in carp by modulating oxidative stress, inflammation, endoplasmic reticulum stress, mitochondrial apoptosis, and autophagy.

Avermectin is one of the widely used anthelmintics in aquaculture and exhibits substantial toxicity to aquatic organisms. Silybin is extensively used for its anti-inflammatory, antioxidant and anti-apoptotic biological properties. Heart is essential for the survival of fish and plays a vital role in pumping blood oxygen and nutrients. Residual avermectin in water poses harm to carp. However, there is still insufficient research on whether silybin can mitigate the toxicity of avermectin to carp heart tissues. In this research, we established a model involving carp subjected to acute avermectin exposure and administered diets containing silybin to explore the potential protective effects of silybin against avermectin-induced cardiotoxicity. The results revealed that avermectin induced oxidative stress, inflammation, endoplasmic reticulum (ER) stress, mitochondrial pathway apoptosis and autophagy in the cardiac tissues of carp. Compared with the avermectin group, silybin significantly reduced ROS accumulation in cardiac tissues, restored antioxidant enzyme activity, inhibited mRNA transcript levels of pro-inflammatory-related factors, and attenuated ER stress, mitochondrial pathway apoptosis and autophagy. Protein-protein interaction (PPI) analysis demonstrated that silybin mitigated avermectin-induced cardiac oxidative stress, inflammation, ER stress, mitochondrial pathway apoptosis and autophagy. Silybin exerted anti-inflammatory effects through the Nuclear Factor kappa B (NF-κB) pathway, antioxidant effects through the Nuclear factor erythroid 2-related factor 2 (Nrf2) - Kelch-like ECH-associated protein 1 (Keap1) pathway, alleviated cardiac ER stress through the Glucose-regulated protein 78 (GRP78)/Activating Transcription Factor 6 (ATF6)/C/EBP homologous protein (CHOP) axis, suppressed apoptosis through the mitochondrial pathway, and inhibited excessive autophagy initiation through the PTEN-induced putative kinase 1 (PINK1)/Parkin RBR E3 ubiquitin protein ligase (PARKIN) signaling pathway. This study provided evidence supporting the protective effect of silybin against avermectin-induced cardiotoxicity in carp, highlighting its potential as a dietary additive to protect fish from adverse effects caused by avermectin exposure.

Protective effect of feed additive ferulic acid on respiratory depression and oxidation imbalance of carp induced by pesticide difenoconazole via ROS/NF-κB/NLRP3 axis.

Difenoconazole (DFZ), classified as a "low-toxicity pesticide," has seen widespread application in recent years. Nevertheless, the non-target toxicity of the substance, particularly towards aquatic creatures, has generated considerable apprehension. The anti-inflammatory and antioxidant effects of Ferulic Acid (FA) have attracted considerable study in this particular setting. This study established a chronic exposure model to DFZ and investigated the protective effects of FA on chronic respiratory inhibition leading to gill damage in freshwater carp. Histological analyses via HE staining indicated that FA effectively alleviated gill tissue damage induced by chronic DFZ exposure. The qRT-PCR results showed that the addition of FA reduced the expression of IL-1ß, IL-6 and TNF-α while boosting the expression of IL-10 and TGF-ß1. Biochemical analyses and DHE staining revealed that FA reduced MDA levels and increased CAT and GSH activities, along with T-AOC, decreased ROS accumulation in response to chronic DFZ exposure. The results obtained from Western blotting analysis demonstrated that the addition of FA effectively suppressed the activation of the NF-κB signalling pathway and the NLRP3 inflammasome pathway in the gills subjected to prolonged exposure to DFZ. In summary, FA ameliorated gill tissue inflammation and blocked ROS accumulation in carp exposed to chronic DFZ, mitigating tissue inflammation and restoring redox homeostasis through the NF-κB-NLRP3 signaling pathway. Hence, the application of FA has been found to be efficacious for improving respiratory inhibition and mitigating gill tissue inflammation and oxidative stress resulting from DFZ pollution in aquatic habitats.

RGMa regulates CCL5 expression via the BMP receptor in experimental autoimmune encephalomyelitis mice and endothelial cells.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Repulsive guidance molecule a (RGMa) has been indicated to act as a bone morphogenetic protein (BMP) co­receptor, enhancing BMP signalling activity. However, the role and downstream pathways of the BMP signalling pathway mediated by RGMa have yet to be fully elucidated. A recent study revealed that C­C motif chemokine ligand 5 (CCL5) has a major role in the pathogenesis of MS via the recruitment of macrophages and T­lymphocytes into the CNS. The present study aimed to evaluate whether RGMa regulates CCL5 via the BMP pathway in MS. The results demonstrated that RGMa regulated CCL5 expression in a BMP ligand­dependent manner in experimental autoimmune encephalomyelitis (EAE) mice in vivo and in endothelial cells in vitro. First, specific inhibition of the expression of RGMa via RNA interference led to a significant reduction of the expression of RGMa and this was associated with a significant delay of EAE, an alleviated disease course and downregulation of CCL5 expression at both the protein and mRNA levels. Furthermore, exogenous noggin, an extracellular antagonist of BMP ligand, abolished the induction effect of RGMa on CCL5 in endothelial cells. Taken together, these results suggested that RGMa is an important regulator of MS and inflammatory mediators such as CCL5, and the present results should prove to be useful in terms of further elucidating the RGMa­BMP receptor signalling pathway and the pathogenesis of RGMa on MS as far as the involvement of blood­brain barrier permeability is concerned.

Support effects on adsorption and catalytic activation of O2 in single atom iron catalysts with graphene-based substrates.

The adsorption and catalytic activation of O2 on single atom iron catalysts with graphene-based substrates were investigated systematically by density functional theory calculation. It is found that the support effects of graphene-based substrates have a significant influence on the stability of the single atom catalysts, the adsorption configuration, the electron transfer mechanism, the adsorption energy and the energy barrier. The differences in the stable adsorption configuration of O2 on single atom iron catalysts with different graphene-based substrates can be well understood by the symmetrical matching principle based on frontier molecular orbital analysis. There are two different mechanisms of electron transfer, in which the Fe atom acts as the electron donor in single vacancy graphene-based substrates while the Fe atom mainly acts as the bridge for electron transfer in double vacancy graphene-based substrates. The Fermi softness and work function are good descriptors of the adsorption energy and they can well reveal the relationship between electronic structure and adsorption energy. This single atom iron catalyst with single vacancy graphene modified by three nitrogen atoms is a promising non-noble metal single atom catalyst in the adsorption and catalytic oxidation of O2. Furthermore, the findings can lay the foundation for the further study of graphene-based support effects and provide a guideline for the development and design of new non-noble-metal single atom catalysts.

[Hydrophilic Surface Modification of Polydimethylsiloxane with UV/Ozone Treatment].

The UV/ozone surface treatment was a simple and low cost hydrophilic modification method. In this paper，UV/ozone treatment is utilized to hydrophilize the surface of PDMS and the results are compared. Contact angle is applied to estimate the effect and stability of the modified surfaces. The results show that the contact angle is around 60° on the PDMS surface with UV/ozone treatment after 12 hours, and it can maintain the surface hydrophilicity in two weeks under ambient atmosphere. The results of FTIR spectroscopy indicate that many chemical functional groups of PDMS surface have been changed with UV/ozone modification, ­CH3 hydrophobic group gradually decrease over time, ­OH and Si­OH hydrophilic groups increase obviously, and the characteristic peaks of SiO2 gradually appear. Through SEM/EDS analysis, it has been found that the major constituent of the surface of PDMS is SiO2 after the surface modification. These results demonstrate that the more hydrophilic groups and the glass-like SiOx layer are formed on the PDMS surface modified with UV/ozone, which enhance the surface hydrophilic and minimize the hydrophobic recovery.

Association of UBQ-8i polymorphism with Alzheimer's disease in Caucasians: a meta-analysis.

BACKGROUND: Several studies have reported an association between the UBQ-8i (rs12344615) polymorphism of the UBQLN1 gene and risk of Alzheimer's disease (AD), but these findings remain controversial. In this study, a meta-analysis was carried out to investigate the relationship between UBQ-8i polymorphism and AD risk and a possible synergy with apolipoprotein E (APOE)ε4 gene status. METHODS: Case-control studies were selected from PubMed, Medline and Embase (Ovid) databases. The potential association was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs). Data were analyzed with Stata version 11.0. RESULTS: A total of 4679 AD cases and 9928 controls were included in the study. There was no evidence of heterogeneity between studies or publication bias in the meta-analysis. There were no significant differences among the examined genetic models. In the analysis stratified by age of onset, a significant association was detected in the late onset AD group under the allele (OR = 1.12, 95% CI: 1.01-1.24), heterozygote (OR = 1.15, 95% CI: 1.02-1.30) and dominant (OR = 1.13, 95% CI: 1.00-1-26) models. However, UBQ-8i polymorphism was not associated with a higher risk for AD among APOEε4 carriers. CONCLUSION: The results suggest that UBQ-8i polymorphism may contribute to AD susceptibility, but does not synergize with APOEε4 status to increase AD risk.

Systematic review of clinical practice guidelines related to multiple sclerosis.

BACKGROUND: High quality clinical practice guidelines (CPGs) can provide clinicians with explicit recommendations on how to manage health conditions and bridge the gap between research and clinical practice. Unfortunately, the quality of CPGs for multiple sclerosis (MS) has not been evaluated. OBJECTIVE: To evaluate the methodological quality of CPGs on MS using the AGREE II instrument. METHODS: According to the inclusion and exclusion criteria, we searched four databases and two websites related to CPGs, including the Cochrane library, PubMed, EMBASE, DynaMed, the National Guideline Clearinghouse (NGC), and Chinese Biomedical Literature database (CBM). The searches were performed on September 20th 2013. All CPGs on MS were evaluated by the AGREE II instrument. The software used for analysis was SPSS 17.0. RESULTS: A total of 27 CPGs on MS met inclusion criteria. The overall agreement among reviews was good or substantial (ICC was above 0.70). The mean scores for each of all six domains were presented as follows: scope and purpose (mean ± SD: 59.05 ± 16.13), stakeholder involvement (mean ± SD: 29.53 ± 17.67), rigor of development (mean ± SD: 31.52 ± 21.50), clarity of presentation (mean ± SD: 60.39 ± 13.73), applicability (mean ± SD: 27.08 ± 17.66), editorial independence (mean ± SD: 28.70 ± 22.03). CONCLUSIONS: The methodological quality of CPGs for MS was acceptable for scope, purpose and clarity of presentation. The developers of CPGs need to pay more attention to editorial independence, applicability, rigor of development and stakeholder involvement during the development process. The AGREE II instrument should be adopted by guideline developers.

Curcumin inhibits mitochondrial injury and apoptosis from the early stage in EAE mice.

The exact pathophysiological change concerning mitochondrial injury and oligodendrocyte apoptosis in MS and EAE model is still unknown. Whether curcumin is able to inhibit mitochondrial injury and suppress the apoptosis in the early stages of MS/EAE is still unclear. We first explored mitochondrial injury and apoptosis at different time points p.i. in C57 BL/6 EAE mice. We then explored the effects of curcumin on mitochondria and apoptosis. Results showed that mitochondrial injury can be observed 3 days p.i. Apoptosis in the spinal cord occurred 3 days p.i. and the apoptotic cells were shown to be oligodendrocytes and neuronal cells. Curcumin significantly reduced the number of apoptotic cells and inhibited the upregulation of cyt-c, caspase-9, and caspase-3 at 7 days p.i. in the EAE mice. These observations demonstrate that mitochondrial injury and oligodendrocyte/neuronal apoptosis occur in the early stages of EAE. Curcumin can inhibit apoptosis in EAE mice which maybe act through protection of mitochondrial injury and inhibition of the intrinsic apoptotic pathway.

Light-emitting-diode-induced fluorescence detection of fluorescent dyes for capillary electrophoresis microchip with cross-polarization method.

A cross-polarization scheme is presented to filter out the excitation light from the emission spectrum of fluorescent dyes using green light emitting diodes as a light source and a linear charge coupled device as an intensity detector. The excitation light was linearly polarized and was then used to illuminate the fluorescent dyes in the microchannels of a capillary electrophoresis microchip. The detector was shielded by the second polarizer, oriented perpendicular to the excitation light. The fluorescent signals from Rhodamine B dyes were measured in a dilution series with resulting emission signals and four different concentrations of fluorescent dyes were detected simultaneously with the same excitation source and detector. A limit-of-detection of 1 µM was demonstrated for Rhodamine B dye under the optimal conditions.

[Reduced irradiation target volume of mediastinal lymph node drainage in conformal radiotherapy for patients with non-small cell lung cancer after thoracic surgery].

OBJECTIVE: To decrease lung and esophageal radiation injuries by reducing irradiation target volume of mediastinal lymph mode drainage in conformal radiotherapy (CRT) for patients with non-small cell lung cancer (NSCLC) after thoracic surgery. METHODS: Fifty-three patients with NSCLC were randomized into groups A and B to receive 3D-CRT after thoracic surgery. Patients in group A, according to conventional therapy, received preventive nodal irradiation (PNI) of the mediastinal lymph node drainage, and those in group B, according to pathological nodal staging after operation, did not have PNI of the metastasis-free area to reduce the clinical target volume (CTV). Patients in both groups were treated with conventional fractionated radiotherapy (CFRT) at 2 Gy in each fraction, and 5 fractions each week. All patients were followed up for two years to record their 2-year survival rate, local relapse of lymph node drainage and lung and esophageal radiation injuries. RESULTS: The total 2-year survival rate was 58.5%in these patients and comparable between the two groups. The rates of local regional relapse and recurrence out of the CTV were 13.8% and 3.4% in group A and 16.7% and 8.3% in group B, respectively (P=1 and P=0.571). The incidence of radiation pneumonia and lung fibrosis were 6.9% and 62.1% in group A and 0% and 58.3% in group B (P=0.459 and P=0.782), and that of radiation esogphagitis and esophagus stricture rates were 27.6% and 6.9% in group A and 12.5% and 4.2% in group B, respectively (P=0.039 and P=1). CONCLUSION: Reduced CTV does not warrant decrease in the local control but may lower the incidence of acute esophageal radiation injury in postoperative patients with NSCLC.

[Relationship between radiosensitivity of nasopharyngeal carcinoma and MDR1 gene polymorphism].

OBJECTIVE: To investigate the relationship between human multidrug resistancel gene (MDR1) polymorphisms and the radiosensitivity of nasopharyngeal carcinoma (NPC). METHODS: Blood samples were collected from 59 NPC patients, who were devided into radiosensitive or radioresistant groups according to their responses to radiation therapy. The genotypes for MDR1 polymorphisms (G2677T in exon 21 and C3435T in exon 26) and their haplotypes were determined by PCR and restriction fragment length polymorphism analysis. The results were further confirmed by sequencing. RESULTS: The 3435CC genotype was associated with a significantly better response to radiotherapy than combined 3435 CT and TT genotype (P=0.026). The 2677GG genotype was also associated with a better response in comparison with combined 2677 GT and TT genotype, but this relation was not statistically significant. Patients with 2677G-3435C haplotype had a significant better response to radiotherapy than those with the other haplotypes (P=0.017). CONCLUSION: The MDR1 G2677T and C3435T polymorphisms may help predict the response to radiotherapy in NPC patients.

[A 16-year clinical observation on 217 chronic HBsAg carriers].

OBJECTIVE: By means of observing the clinical development of asymptomatic chronic HBsAg carriers (AsC) to explore the clinical rule of development of chronic hepatitis B (CHB) to liver cirrhosis (LC) to hepatocellular carcinoma (HCC) and to seek effective method for blocking the procedure. METHODS: AsCs were selected from health examination according to the diagnostic standard from the National Program for Prevention and Treatment of Viral Hepatitis, by periodical or non-periodical conventional examination of liver diseases, mixed infection of HCV was excluded. A 16-year systematic observation on clinical process of HBV infection series was completed. RESULTS: In the 217 AsCs observed, 21 cases (9.68%) with the HBsAg negatively converted, the average year negative conversion rate being 0.58%, among them, 13/21 cases (61.9%) had production of anti-HBs antigen; 20 cases were clinically cured; 1 case transferred to HCC; 124 cases (57.14%) remained asymptomatic carriers; 73 transferred to chronic liver disease, showing a tendency of gradually developing from CHB to LC to HCC, the year transferring rate from AsC to LC and HCC being 1.04% and 0.40%, respectively. Fifteen patients died of liver diseases, in which one died of severe CHB, 3 of LC and 11 of HCC. CONCLUSION: Different clinical end-results may reveal in AsCs according to their age and regulation on immune response to HBV. Few of the HCC and LC patients were HBeAg (e+) positive, they often reveal HBeAg (e-) negative or anti-HBe positive. HCC always develops on the basis of liver fibrosis or cirrhosis, which are the prophase of HCC, and patients with liver fibrosis or cirrhosis are the high risk group of developing HCC. HCC is not only the terminal pathologic stage of hepatopathy, but also one of the most important factors that causes death of chronic hepatopathy. From the viewpoint of integrative medicine in typing hepatopathy to observe the clinical speciality of AsC developing to CHB, LC and HCC, it is considered that the degree of blood stasis is in accordance with the development of hepatopathy.

Therapeutic effect of three-dimensional conformal radiotherapy on locally advanced pancreatic carcinoma.

OBJECTIVE: To evaluate the effects of the two conformal radiotherapy modalities in the treatment of locally advanced pancreatic carcinoma. METHODS: From October, 1998 to June, 2001, 67 patients with locally advanced pancreatic carcinoma received conformal radiotherapy (CRT). Vacuum cushions were applied to immobilize the patients before contrast CT scans, the treatment plans were simulated by three-dimensional treatment planning system. The patients were randomized into group A to receive a total dose of 45-54 Gy given in 8-12 fractions completed in 18-27 d and group B with a total dose of 45-54 Gy in 15-18 fractions within 20-25 d. RESULTS: The partial and complete pain relief rates of the two groups were 95.9% and 81.6%, respectively, one month after the completion of the radiotherapy, with a median survival of 12.5 months. The response rates of the patients and the 2-year overall survival rates in group A were 81.8% and 51.6%, respectively, and were 35.3% and 12.1% in group B. The low-dose fractionated CRT was superior than accelerated CRT. CONCLUSION: For patients with unresectable pancreatic cancer receiving low-dose fractionated CRT, a high dose targeted at the tumor can be given in a fraction and the normal surrounding tissues are exposed to low-dose radiation, to achieve good therapeutic effect with minimized adverse effects on normal tissues in relation to the exposure.

Etiological analysis of the sequelae of radiotherapy for nasopharyngeal carcinoma: a follow-up study of 112 cases.

OBJECTIVE: To explore the etiology of the sequelae of radiotherapy for nasopharyngeal carcinoma (NPC) so as to find the possible means for reducing or preventing its occurrence. METHODS: A total of 112 pathologically confirmed patients with nasopharyngeal carcinoma, who had survived for 5 years following the radiotherapy, were included in this study. Sixty-four patients with the primary carcinoma in the nasopharyngeal region received radiotherapy with the radiation field covering the bilateral anterior ear regions, and in the other 48 patients, adjuvent exposure of the anterior nasal region was administered. The metastases in the cervical lymph nodes were exposed to tangential radiation by 40 Gy X-ray followed by approximately 20 Gy vertical electron beam exposure. RESULTS: Limited mouth-opening and dry mouth occurred mostly during the first 2 years after radiotherapy, and hearing loss in the first year. Neck fibrosis tended to increase with the time elapse after the therapy, and posterior cranial nerve damages showed no signs of time-related occurrence. It was found that the occurrence of neck fibrosis, dry mouth and the nerve injuries did not obviously correlate with the dosage of X-ray exposure in the anterior ear regions, while limited mouth-opening and the hearing loss increased with the radiation dosage. The sequelae did not arise from different radiation field selection as adopted in this study. CONCLUSION: The radiation dose should be controlled at around 70 Gy for NPC treatment, and for carcinoma remnant in the nasopharyngeal region, additional dose in the cavity would be appropriate. When the X-ray dose of 65 Gy in the neck region fails to result in satisfactory recession of lymph node metastasis, comprehensive treatment involving multiple modalities should be considered.