Immunological gadolinium-doped mesoporous carbon nanoparticles for tumor-targeted MRI and photothermal-immune co-therapy.

Photothermal therapy (PTT) is an effective and well-documented approach to thermally ablate tumors. However, the side effect of distal metastasis and recurrence limit its further expansion. At the same time as PTT was developed, the employment of imaging to monitor the treatment of tumors also became meaningful. Herein, as a proof of concept, gadolinium-doped mesoporous carbon nanoparticles (Gd-MCNs) were prepared as nanocarriers, MRI contrast agents, and PTT agents by a one-step hard template method, which realized Gd doping and carbon filling simultaneously, while retaining enough pore space for drug loading. After loading the immune adjuvant, R837, and the coating of tumor extracellular vesicle, the obtained biomimetic nanoparticles (EV@Gd-MCNs-R837) not only allowed tumor MRI, but also inhibited the primary tumor and its metastasis with long-term immune memory in vivo. This study provides proof for the potential of Gd-MCNs-based biomimetic nanoparticles for targeted PTT/immune-enhanced synergistic theranostic of tumors.

Cadmium-mediated miR-30a-GRP78 leads to JNK-dependent autophagy in chicken kidney.

Cadmium-mediated microRNAs have become a heavily researched topic. Few studies mention the regulation of autophagy by cadmium through microRNAs, especially regarding poultry. The kidney is one of the organs most severely affected by cadmium, as it is involved in the accumulation of metal ions; causing such types of damage as apoptosis, necrosis and autophagy to the body. However, the relationship between miR-30a and GRP78 in the chicken kidney during ER stress and autophagy via JNK has not been thoroughly elucidated to date. In our research, we randomly assigned 128 Hy-Line Brown laying chickens to four groups with different diet treatments. The four groups consisted of the control group (0.2 mg Se kg-1), the Se group (2 mg kg-1 of Na2SeO3), the Se + Cd group (150 mg kg-1 of CdCl2 and 2 mg kg-1 of Na2SeO3) and the Cd group (150 mg kg-1 of CdCl2). On the 90th day, we detected the expression of miR-30a, GRP78, ER stress-related genes, IRE-1-JNK and autophagy-related genes. Compared with the control group, the mRNA levels of IRE-1-JNK, ER stress-related genes, autophagy-related genes and GRP78 were significantly increased (P < 0.05), while the expression of miR-30a was significantly decreased (p < 0.05) in the Cd group. However, those changes were clearly alleviated in the Se + Cd group (p < 0.05). In summary, we demonstrated that Cd triggered an miR-30a-GRP78 signaling axis disorder, increasing ER stress and activating the IRE-1-JNK pathway, thereby promoting autophagy in the chicken kidney. Moreover, Se could antagonize the negative impact of Cd.

The Antagonistic Effect of Selenium on Lead-Induced Immune Dysfunction via Recovery of Cytokine and Heat Shock Protein Expression in Chicken Neutrophils.

Lead (Pb) is a ubiquitous and toxic heavy metal and it can damage the immune system in humans and animals. Many researchers have reported that Selenium (Se) could possess various pharmacological effects in mammals. However, few studies have been carried out to investigate the protective role of Se in birds, especially in chickens. In this study, we investigated the protective effects of Se against Pb-induced inflammatory responses and the expression of heat shock proteins (HSPs) in peripheral blood neutrophils. One hundred eighty Hy-Line brown chickens were randomly divided into the control group (Con group), Se supplementation group (+Se group), Pb supplementation group (+Pb group), and the Se and Pb compound group (Se+Pb group). On the 90th day of the experiment, the peripheral blood was collected to extract neutrophils, and then, the levels of HSPs and cytokines were examined. The results showed that, after Pb treatment, the levels of IL-(1ß, 1R, 4, 8, 10, and 12ß), TGF-ß4, and HSP (27, 40, 60, 70, and 90) mRNA were significantly increased and levels of IL-2 and IFN-γ mRNA were decreased compared with those in the control group. Compared with the control group, the protein levels of HSP60 and HSP70 were also increased in the Pb treatment group. Co-administration of Se (1 mg/kg/day) and Pb resulted in a reversal of the Pb-induced cytokine changes in neutrophils accompanied by a significant decrease in HSPs. Our study demonstrated that Pb could decrease the immune function via changing the expression of cytokines and HSPs in chicken neutrophils, but Se could relieve the toxic effect induced by Pb.

Inflammatory Response Occurs in Veins of Broiler Chickens Treated with a Selenium Deficiency Diet.

Selenium (Se) has been indicated to prevent chronic diseases including cancer, cardiovascular disease, and type 2 diabetes. However, a few studies have indicated that Se deficiency can induce vascular diseases. Thus, in the present study, we investigated the effect of Se deficiency on vascular pathology. A total of 60 male broiler chickens were randomly divided into 2 groups (n = 30). The control group (C group) was fed a basic diet, and the Se-deficient group (L group) was fed a Se-deficient, corn-soy-based diet. Changes in messenger RNA (mRNA) and protein levels of inflammatory factors and inflammation-related cytokines were examined by both RT-PCR and Western blot analysis. Our results indicate that the mRNA and protein levels of inflammatory factors and inflammation-related cytokines in the L group were significantly changed in the vein. In addition, principal component analysis (PCA) was used to define the most important parameters that could be used as key factors. The in vitro experiments also demonstrated that Se can enhance the anti-inflammatory ability of vein endothelial cells. In conclusion, Se deficiency induces an inflammatory response by modulating inflammatory factors and inflammation-related cytokines.

Effects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils.

Lead (Pb) is one of the most highly toxic metal pollutant that can cause damage to the immune system. It is known that selenium (Se) can antagonize heavy metals. To explore the toxic effects of Pb poisoning on bird immune cells, as well as the alleviating effects of Se on Pb, Se supplement and/or Pb poisoning chicken models were established. One hundred and eighty Hyline 7-day-old male chickens received either Se (1mg Se per kg of diet), Pb (350mg Pb per liter water) or Se+Pb in their diet and water for 90 days. Then, whole blood was collected from the four groups of chickens, and serum and neutrophils were isolated. The levels of Se and Pb in chicken serum, mRNA levels of 24 selenoproteins (GPX1, GPX2, GPX3, GPX4, Dio1, Dio2, Dio3, Txnrd1, Txnrd2, Txnrd3, SELS, SPS2, SELK, SELW1, SEP15, SEPX1, SELT, SELI, SELO, SELM, SEPN1, SEPP1, SELU, SELH) and inflammatory factors (TNF-α, COX-2, iNOS, NF-κB), and iNOS protein level in chicken neutrophils were determined, and protein-protein interaction prediction and principal component analysis were performed. The data showed that Pb exposure increased Pb content in serum, activated the NF-κB pathway, and increased the expression of selenoproteins in chicken neutrophils. Se supplements could reduce Pb concentration in serum, had a mitigative effect on the activation of the NF-κB pathway and further enhanced the upward trend of selenoprotein expression induced by Pb exposure. These results suggest that Se supplement could eliminate Pb in serum and alleviate the activation of the NF-κB pathway under Pb exposure by increasing the expression of selenoproteins.