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Copper (Cu) is an essential micronutrient for both humans and animals; however, excessive intake of Cu can be immunotoxic. There are limited studies on spleen toxicity induced by Cu. This study was conducted to investigate the effects of Cu on spleen oxidative stress, apoptosis, and inflammatory responses in mice orally administered with 0 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of CuSO4 for 42 days. As discovered in this work, copper sulfate (CuSO4) reduced the activities of antioxidant enzymes (SOD, CAT, and GSH-Px), decreased GSH contents, and increased MDA contents. Meanwhile, CuSO4 induced apoptosis by increasing TUNEL-positive cells in the spleen. Also, CuSO4 increased the expression of γ-H2AX, which is the marker of DNA damage. Concurrently, CuSO4 caused inflammation by increasing the mRNA levels of interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). In conclusion, the abovementioned findings demonstrate that over 10 mg/kg CuSO4 can cause oxidative stress, apoptosis, DNA damage, and inflammatory responses, which contribute to spleen dysfunction in mice.

Nickel (Ni) is a widely distributed metal in the environment and an important pollutant due to its widespread industrial applications. Ni has various toxicity in humans and experimental animals, including carcinogenicity. However, the carcinogenic effects of Ni remain troublesome. Cell cycle dysregulation may be an important carcinogenic mechanism and is also a potential molecular mechanism for Ni complexes anti-cancerous effects. Therefore, we conducted a literature review to summarize the effects of Ni on cell cycle. Up to now, there were three different reports on Ni-induced cell cycle arrest: (i) Ni can induce cell cycle arrest in G0/G1 phase, phosphorylation and degradation of IkappaB kinase-alpha (IKKα)-dependent cyclin D1 and phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway-mediated down-regulation of expressions of cyclin-dependent kinases 4 (CDK4) play important role in it; (ii) Ni can induce cell cycle arrest in S phase, but the molecular mechanism is not known; (iii) G2/M phase is the target of Ni toxicity, and Ni compounds cause G2/M cell cycle phase arrest by reducing cyclinB1/Cdc2 interaction through the activation of the ataxia telangiectasia mutated (ATM)-p53-p21 and ATM-checkpoint kinase inhibitor 1 (Chk1)/Chk2-cell division cycle 25 (Cdc25) pathways. Revealing the mechanisms of cell cycle dysregulation associated with Ni exposure may help in the prevention and treatment of Ni-related carcinogenicity and toxicology.

In recent years, NADC34-like PRRSV had a strong impact on the pig industry in the United States and Peru; it was also detected in northeastern China in 2017. In this study, we conducted a retrospective survey of NADC34-like PRRSV in Southwest China from 2016 to 2020. Five NADC34-like PRRSV strains were detected in samples and their whole genomes were sequenced, designated as CHSCMY-22019, CHSCYB-32020, CHSCMS-42020 and CHSCLS-22020. This is the first discovery and report of an NADC34-like PRRSV strain in Southwest China. Phylogenetic tree analysis based on the whole genome showed that the five NADC34-like PRRSV strains belonged to sub-lineage 1.5 of PRRV-2. They had 100 aa deletions in the Nsp2 hypervariable region of VR2332, located at 329-428 aa, similar to the US isolate IA/2014/NADC34. Recombination analysis showed that CHSCCD-42020 strain was the recombinant strain of QYYZ strain and IA/2014/NADC34 strain in China. The emergence of NADC34-like PRRSV strains in Southwest China indicates a potential threat to PRRS prevention and control in pigs. This study improves our understanding of the epidemic status and genetic variation of NADC34-like PRRSV strains in China.

Copper (Cu) is an essential micronutrient for both human and animals. However, excessive intake of copper will cause damage to organs and cells. Inflammation is a biological response that can be induced by various factors such as pathogens, damaged cells, and toxic compounds. Dysregulation of inflammatory responses are closely related to many chronic diseases. Recently, Cu toxicological and inflammatory effects have been investigated in various animal models and cells. In this review, we summarized the known effect of Cu on inflammatory responses and sum up the molecular mechanism of Cu-regulated inflammation. Excessive Cu exposure can modulate a huge number of cytokines in both directions, increase and/or decrease through a variety of molecular and cellular signaling pathways including nuclear factor kappa-B (NF-κB) pathway, mitogen-activated protein kinase (MAPKs) pathway, JAK-STAT (Janus Kinase- signal transducer and activator of transcription) pathway, and NOD-like receptor protein 3 (NLRP3) inflammasome. Underlying the molecular mechanism of Cu-regulated inflammation could help further understanding copper toxicology and copper-associated diseases.

Obesity is a risk factor of many diseases, but could be beneficial to the individuals with bacterial infection. The present study was conducted to investigate the relationship between obesity and heart during nonfatal bacterial infection. Male normal (lean) and diet-induced obesity mice (DIO, fed with high-fat diet) were chosen to perform nasal instillation with E. coli to establish a nonfatal acute mouse model. The cardiac histopathology, inflammation and oxidative damage, as well as apoptosis were detected post-infection. The results revealed that the Escherichia coli (E.coli)-infected mice exhibited increased cardiac index, contents of IL-1β, IL-6, IL-8, TNF-α, leptin and resistin, levels of apoptotic proteins (caspase-3 and caspase-9, and bax/bcl-2 ratio), cardiac pathological changes and oxidative stress. Furthermore, these parameters were more serious in the lean mice than those in the DIO mice. In summary, our findings gave a new sight that E.coli infection impaired heart via histopathological lesions, inflammation and oxidative stress and excessive apoptosis of cardiomyocytes. Interestingly, obesity exerted attenuated effects on the heart of mice with non-fatal infection of E.coli through decreased inflammation, oxidative stress and apoptosis of cardiac tissue.

Copper (Cu) is a necessary micronutrient at lower concentration, while excessive Cu exposure or Cu homeostasis disorders can lead to toxicity. The mechanism of male reproductive toxicity induced by Cu is still unknown. This study aims to investigate whether autophagy plays an important role in copper-induced spermatogenesis disorder in vivo and vitro. The present study showed that copper sulfate (CuSO4) might significantly promote autophagy level in the testis and mouse-derived spermatogonia cell line GC-1 spg cells. Concurrently, CuSO4 could induce autophagy via AMPK-mTOR pathway that downregulated p-mTOR/mTOR and subsequently upregulated p-AMPKα/AMPKα as well as p-ULK1/ULK1. In the meanwhile, CuSO4 treatment could also increase expression levels of the autophagy-related proteins. Then, the role of oxidative stress in CuSO4-induced autophagy was investigated. The findings demonstrated that oxidative stress inhibitor (NAC) attenuated CuSO4-induced autophagy in vivo and vitro, reversing the activation for AMPK-mTOR pathway. Additionally, the study also investigated how autophagy worked under the spermatogenesis disorder induced by CuSO4. Inhibition of autophagy could decrease cell viability, and enhance the ROS accumulation and apoptosis in the GC-1 cells, meanwhile, the spermatogenesis disorder, oxidative stress and histopathological changes were increased in the testis. Furthermore, co-treatment with the apoptosis inhibitor (Z-VAD-FMK) could decrease the spermatogenesis disorder but not influence autophagy. Besides, the crosslink between autophagy and ferroptosis were also measured, the data showed that inhibition of autophagy could suppress CuSO4-induced ferroptosis in in vivo and vitro. Altogether, abovementioned results indicated that CuSO4 induced autophagy via oxidative stress-dependent AMPK-mTOR pathway in the GC-1 cells and testis, and autophagy activation possibly led to the generation of protection mechanism through oxidative damage and apoptosis inhibition, however, autophagy also aggravate CuSO4 toxicology through promoting ferroptosis. Overall, autophagy plays a positive role for attenuating CuSO4-induced testicular damage and spermatogenesis disorder. Our study provides a possible targeted therapy for Cu overload-induced reproduction toxicology., Graphical abstract Image 1, Highlights • CuSO4-treatment could induce autophagy through AMPK-mTOR pathway. • Oxidative stress is an essential inducer of CuSO4-induced autophagy. • Autophagy inhibits oxidative damage and apoptosis in the testis of CuSO4-treatment mice. • Autophagy promotes ferroptosis in the testis of CuSO4-treatment mice. • Autophagy plays a protective role in copper-induced spermatogenesis disorder.

JEV is one of the zoonotic pathogens that cause serious diseases in humans. JEV infection can cause abortion, mummified foetus and stillbirth in sows, orchitis and semen quality decline in boars, causing huge economic losses to pig industry. In order to investigate the epidemiology of JEV in pigs in Sichuan province, a rapid and efficient fluorescent Reverse transcription recombinase-aided amplification (RT-RAA) detection method was established. Aborted fetuses and testicular swollen boar samples were detected by RT-RAA in pigs in the mountain areas around Sichuan Basin, and the detection rate of JEV was 6.49%. The positive samples were identified as JEV GI strain and GIIIstrain by sequencing analysis. We analyzed the whole gene sequence of a positive sample for the GI virus. The Envelope Protein (E protein) phylogenetic tree analysis was far related to the Chinese vaccine strain SA14-14-2, and was most closely related to the JEV GI strains SH17M-07 and SD0810 isolated from China. The results showed that we established an efficient, accurate and sensitive method for clinical detection of JEV, and JEV GI strains were prevalent in Sichuan area. It provides reference for the prevention and control of JEV in Sichuan.

Multi-drug-resistant

GETV, an arbo-borne zoonotic virus of the genus Alphavirus, which causes diarrhea and reproduction disorders in swine, lead to serious economic losses to the swine industry in China. At present, the existing methods for GETV detection are time-consuming and low sensitivity, so, a rapid, accurate and sensitive GETV detection method is urgently needed. In this study, a fluorescent reverse transcription recombinase-assisted amplification method (RT-RAA) was successfully established for the rapid detection of GETV. The sensitivity of this method to GETV was 8 copies/reaction and 20 TCID50/reaction. No cross-reaction with other viruses. A total of 118 samples were prepared for GETV detection using fluorescent RT-RAA and SYBR Green I RT-qPCR, the coincidence rate of the two methods was 100%. The results suggest that the RT-RAA method is rapid, sensitive and specific for GETV detection and can be applied in the clinical.

Due to the physiological characteristics of piglets, the morphological structure and function of the small intestinal mucosa change after weaning, which easily leads to diarrhea in piglets. The aim of this study was to investigate effects of crude protein (CP) levels on small intestinal morphology, occludin protein expression, and intestinal bacteria diversity in weaned piglets. Ninety-six weaned piglets (25 days of age) were randomly divided into four groups and fed diets containing 18%, 20%, 22%, and 24% protein. At 6, 24, 48, 72, and 96 h, changes in mucosal morphological structure, occludin mRNA, and protein expression and in the localization of occludin in jejunal and ileal tissues were evaluated. At 6, 24, and 72 h, changes in bacterial diversity and number of the ileal and colonic contents were analyzed. Results showed that structures of the jejunum and the ileum of piglets in the 20% CP group were intact. The expression of occludin mRNA and protein in the small intestine of piglets in the 20% CP group were significantly higher than those in the other groups. As the CP level increased, the number of pathogens, such as

Autophagy and apoptosis play important roles in the occurrence and development of diseases. Largemouth bass virus (LMBV) is a primary agent that causes infectious skin ulcerative syndrome in largemouth bass and threatens the aquaculture of the species. We investigated the relationship between LMBV and autophagy, as well as the effect of autophagy on apoptosis induced by LMBV. Results showed that LMBV could induce autophagy in epithelioma papulosum cyprinid (EPC) cells. There was also an increase in LC3-II protein and decrease in p62 protein, along with autophagosome-like membranous vesicles and punctate autophagosomes fluorescent spots being observed in EPC cells. Enhancing autophagy inhibited the replication of LMBV and apoptosis in EPC cells while inhibiting autophagy produced the opposite effect. These results offer new insights into the pathogenesis of LMBV and anti-LMBV strategies.

Background Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the swine industry globally. Evaluation of antibody responses and neutralizing antibody titers is the most effective method for vaccine evaluation. In this study, the B cell line epitopes of PRRSV M protein were predicted, and two peptide ELISA assays were established (M-A110-129 ELISA, M-A148-174 ELISA) to detect antibodies against PRRSV M protein. Field serum samples collected from pig farms were used to validate the peptide ELISA and compare it with an indirect immunofluorescence assay. Results The sensitivity and specificity of M-A110-129 ELISA and M-A148-174 ELISA were (111/125) 88.80%, (69/70) 98.57% and (122/125) 97.60%, (70/70) 100%, relative to indirect immunofluorescence assay. This peptide ELISA could detect antibodies against different genotypes of PRRSV including type 1 PRRSV, classical PRRSV, HP-PRRSV, and NADC30 like PRRSV, but not antibodies against other common swine viruses. The results of ROC analysis showed that the area under the curve (AUC) of the M-A110-129 ELISA and M-A148-174 ELISA were 0.967 and 0.996, respectively. Compared the concordance of results using two peptide ELISA assays, the IDEXX PRRSV X3 Ab ELISA and a virus neutralization test, were assessed using a series of 147 sera from pigs vaccinated with the NADC30-like PRRSV inactivated vaccine. The M-A148-174 ELISA had the best consistency, with a Cohen’s kappa coefficient of 0.8772. The concordance rates of the Hipra PRRSV ELISA kit, M-A110-129 ELISA and M-A148-174 ELISA in the field seropositive detection results were 91.08, 86.32 and 95.35%, relative to indirect immunofluorescence assay. Conclusions In summary, compared with M-A110-129 ELISA, the PRRSV M-A148-174 ELISA is of value for detecting antibodies against PRRSV and the evaluation of the NADC30-like PRRSV inactivated vaccine, but the advantage is insufficient in serological early diagnosis.

In order to pursue faster growth and development of weaned piglets, increased dietary protein (CP) levels were favoured by the pig industry and the feed industry. The digestive organs of piglets were not fully developed at weaning, and the digestive absorption capacity of protein was limited. High-protein diets can cause allergic reactions in piglets, destroy intestinal structural integrity, reduce immunity, and cause intestinal flora imbalance. Undigested proteins were prone to produce toxic substances, such as ammonia and biogenic amines, after fermentation in the hindgut, which negatively affects the health of the intestine and eventually causes reduced growth performance and diarrhoea in piglets. This review revealed the mechanism of diarrhoea caused by high-protein diets in weaned piglets and provided ideas for preventing diarrhoea in weaned piglets.

The study aimed to perform a regional investigation of the antibiotic resistance characteristics (ARCHs) of zoonotic pathogens in environments of high antibiotic pressure to observe the future trend of antibiotic application. In this study, an ARCH analysis of the animal pathogens was conducted in the Sichuan Basin with an area of about 180,000 km

The aim of this study was to investigate the effects of different doses of selenium (Se) on oxidative damage and neurotransmitter-related parameters in arsenic (As)-induced broiler brain tissue damage. Two hundred 1-day-old avian broilers were randomly divided into five groups and fed the following diets: control group (As 0.1 mg/kg + Se 0.2 mg/kg), As group (As 3 mg/kg + Se 0.2 mg/kg), low-Se group (As 3 mg/kg + Se 5 mg/kg), medium-Se group (As 3 mg/kg + Se 10 mg/kg), and high-Se group (As 3 mg/kg + Se 15 mg/kg). Glutathione (GSH), glutathione peroxidase (GSH-PX), nitric oxide (NO), nitric oxide synthase (NOS) activity, glutamate (Glu) concentration, glutamine synthetase (GS) activity, acetylcholinesterase (TchE) activity, and the apoptosis rate of brain cells were measured. The results showed that 3 mg/kg dietary As could induce oxidative damage and neurotransmitter disorder of brain tissue, increase the apoptosis rate of brain cells and cause damage to brain tissue, decrease activities of GSH and GSH-PX, decrease the contents of NO, decrease the activities of iNOS and tNOS, increase contents of Glu, and decrease activities of Gs and TchE. Compared with the As group, the Se addition of the low-Se and medium-Se groups protected against As-induced oxidative damage, neurotransmitter disorders, and the apoptosis rate of brain cells, with the addition of 10 mg/kg Se having the best effect. However, 15 mg/kg Se not only did not produce a protective effect against As damage but actually caused similar or severe damage.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating viral diseases in the global pig industry. Recently, we isolated and plaque-purified porcine reproductive and respiratory syndrome virus (PRRSV) strain SC2020-1 from “aborted piglets” on a farm in Sichuan, China. To investigate the molecular biological characteristics of this strain, it was subjected to genome sequencing and analysis. The full-length genome sequence of strain SC2020-1 was 87.7% identical to that of the Lelystad strain (PRRSV type I protoype strain) and 82.2-84.8% identical to PRRSV type I isolates from China. NSP2, ORF3, and ORF4 were the most variable regions and contained discontinuous deletions or insertions when compared to other PRRSV type I strains. Phylogenetic analysis of the complete genome sequence showed that SC2020-1 clustered with PRRSV type I but outside of the three previously described branches (Lelystad virus-like, Amervac PRRS-like, and BJEU06-1-like). The Nsp2 gene was in the same branch with EUGDHD strains from China. This is the first report of PRRSV type I infection associated with abortion in sows in southwest China. Close attention should be paid to the prevention and control of this evolving virus.

This study aimed to determine the effects of selenium on the immune toxicity of subacute arsenic poisoning in chickens. Two hundred 8-day-old broilers were randomly divided into 5 groups: the control group (0.1 mg/kg As + 0.2 mg/kg Se), the As group (3 mg/kg As + 0.2 mg/kg Se), As + Se group I (3 mg/kg As + 5 mg/kg Se), As + Se group II (3 mg/kg As + 10 mg/kg Se), and As + Se group III (3 mg/kg As + 15 mg/kg Se). The conclusions were drawn based on the following measurements: 3.0 mg/kg added to feed led to a decrease in the growth performance of the broilers, reduced the level and conversion rate of ANAE, reduced the blood protein content of the broilers but had no effect on the albumin/globulin ratio, and had an inhibitory effect on erythrocyte immunity. Selenium-added of 5 and 10 mg/kg in daily feed leads to increased growth performance, increases the positive rate and conversion rate of ANAE, increases the hemoglobin content of broilers, and promotes erythrocyte immunity, which indicates that the selenium-added reduces the toxic effects of arsenic; 3.0 mg/kg arsenic with 15 mg/kg selenium had the most severe toxic effects. Fifteen milligrams per kilogram of selenium added in daily feed increases the toxicity of arsenic to broilers. The dose of 10 mg/kg selenium showed the best inhibitory effect on subacute arsenic poisoning in the broilers.

Copper is considered as an indispensable trace element for living organisms. However, over-exposure to Cu can lead to adverse health effects on human. In this study, CuSO4 decreased sperm concentration and motility, increased sperm malformation rate. Concurrently, testicular damage including testicular histopathological aberrations and reduction of testis relative weight were observed. Then, the mechanism underlying Cu-induced testicular toxicity was explored. According to the results, CuSO4 elevated ROS production while reducing antioxidant function. Additionally, CuSO4 induced apoptosis which was featured by MMP depolarization and up-regulated levels of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, caspase-12, cleaved-PARP and Bax, whereas down-regulated Bcl-2 expression. Meanwhile, CuSO4 caused testis DNA damage (up-regulation of γ-H2AX protein expression) and suppressed DNA repair pathways including BER, NER, HR, MMR, together with the NHEJ repair pathways, yet did not affect MGMT. To investigate the role of oxidative stress in CuSO4-induced apoptosis and DNA damage, the antioxidant NAC was co-treated with CuSO4. NAC attenuated CuSO4-induced ROS production, inhibited apoptosis and DNA damage. Furthermore, the spermatogenesis disorder was also abolished in the co-treatment with CuSO4 and NAC group. Altogether, abovementioned results indicated that CuSO4-induced spermatogenesis disorder is related to oxidative stress-mediated DNA damage and germ cell apoptosis, impairing male reproductive function.

Although copper is among the indispensable trace elements in animal physiological processes, it exerts toxicity upon over-exposure. The present study aimed to investigate hepatocyte autophagy induced by CuSO4 and its potential mechanism. A total of 240 ICR mice (four-week-old, 120 males and 120 females) were randomly divided into four groups, in which mice separately received 0, 4, 8, and 16 mg/kg of Cu (Cu2+-CuSO4) for 42 d. The results of increased autophagosomes and autophagy marker LC3B brown cell staining showed that excessive intake of Cu enhanced hepatocyte autophagy. Simultaneously, Cu inhibited the activity of mTOR through suppressing mRNA and protein expressions in mTOR, which in turn up-regulated expression levels of ULK1 and initiated autophagy. Also, over-exposure to Cu increased mRNA and protein expressions of Beclin1, Atg12, Atg5, Atg16L1, Atg7, Atg3, and LC3 and decreased mRNA and protein expressions of p62. These results indicate that excess Cu can enhance hepatocyte autophagy via inhibiting the mTOR signaling pathway and regulating mRNA and protein expressions of factors implicated to autophagy in mice.

Background/Aims: Excessive fluoride intake can induce cytotoxicity, DNA damage and cell-cycle changes in many tissues and organs, including the kidney. However, the underlying molecular mechanisms of fluoride-induced renal cell-cycle changes are not well understood at present. In this study, we used a mouse model to investigate how sodium fluoride (NaF) induces cell-cycle changes in renal cells. Methods: Two hundred forty ICR mice were randomly assigned to four equal groups for intragastric administration of NaF (0, 12, 24 and 48 mg/kg body weight/day) for 42 days. Kidneys were taken to measure changes of the cell-cycle at 21 and 42 days of the experiment, using flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods. Results: NaF, at more than 12 mg/kg body weight, induced G2/M phase cell-cycle arrest in the renal cells, which was supported by the finding of significantly increased percentages of renal cells in the G2/M phase. We found also that G2/M phase cell-cycle arrest was accompanied by up-regulation of p-ATM, p-Chk2, p-p53, p-Cdc25C, p-CDK1, p21, and Gadd45a protein expression levels; up-regulation of ATM, Chk2, p53, p21, and Gadd45a mRNA expression levels; down-regulation of CyclinB1, mdm2, PCNA protein expression levels; and down-regulation of CyclinB1, CDK1, Cdc25C, mdm2, and PCNA mRNA expression levels. Conclusion: In this mouse model, NaF, at more than 12 mg/ kg, induced G2/M phase cell-cycle arrest by activating the ATM-Chk2-p53/Cdc25C signaling pathway, which inhibits the proliferation of renal cells and development of the kidney. Activation of the ATM-Chk2-p53/Cdc25C signaling pathway is the mechanism of NaF-induced renal G2/M phase cell-cycle arrest in this model.

Fluorine or fluoride can have toxic effects on bone tissue and soft tissue at high concentrations. These negative effects include but not limited to cytotoxicity, immunotoxicity, blood toxicity, and oxidative damage. Apoptosis plays an important role in fluoride-induced toxicity of kidney, liver, spleen, thymus, bursa of Fabricius, cecal tonsil, and cultured cells. Here, apoptosis activated by high level of fluoride has been systematically reviewed, focusing on three pathways: mitochondrion-mediated, endoplasmic reticulum (ER) stress-mediated, and death receptor-mediated pathways. However, very limited reports are focused on the death receptor-mediated apoptosis pathways in the fluoride-induced apoptosis. Therefore, understanding and discovery of more pathways and molecular mechanisms of fluoride-induced apoptosis may contribute to designing measures for preventing fluoride toxicity.

Fluoride is known to impair organism's development and function via adverse effects, and autophagy plays a regulation role in human or animal health and disease. At present, there are no reports focused on fluoride-induced autophagy in the animal and human spleen. The objective of this study was to investigate sodium fluoride (NaF)-induced splenocyte autophagy and the potential mechanism via regulation of p-mTOR in growing mice by using the methods of transmission electron microscopy (TEM), immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A total of 240 ICR mice were equally allocated into four groups with intragastric administration of distilled water in the control group and 12, 24, 48 mg/kg NaF solution in the experimental groups for 42 days. Results revealed that NaF increased autophagosomes or autolysosomes in spleen. Simultaneously, the autophagy marker LC3 brown punctate staining was increased with NaF dosage increase. On the other hand, NaF caused inhibition of mTOR activity, which was characterized by down-regulation of PI3K, Akt and mTOR mRNA and protein expression levels. And the suppression of mTOR activity in turn resulted in the significantly increased of ULK1 and Atg13 expression levels. Concurrently, NaF increased the levels of mRNA and protein expression of autophagy markers LC3, Beclin1, Atg16L1, Atg12, Atg5 and decreased the mRNA and protein expression levels of p62. The above-mentioned findings verify that NaF induces autophagy via mTOR signaling pathway. The inhibition of mTOR activity and alteration of autophagy-related genes and proteins are the potential molecular mechanism of NaF-induced splenocyte autophagy.

As an extensively environmental pollution, Nickel (Ni) represents a serious hazard to human health. The present study focused on exploring the mechanism of Ni-mediated nephrotoxicity, such as apoptosis, autophagy and oxidative stress. In the current work, NiCl2 treatment could induce kidney damage. Meanwhile, NiCl2 treatment elevated ROS production and MDA content and suppressed the antioxidant activity, which was characterized by reducing T-AOC, CAT, SOD activity and GSH content. For investigating the role of oxidative stress on NiCl2-mediated nephrotoxicity, N-acetyl cysteine (NAC, effective antioxidant and free radical scavenger) was co-treated with NiCl2. The results showed that NAC significantly suppressed the NiCl2-mediated oxidative stress and mitigated NiCl2-induced the kidney damage. Then, whether oxidative stress-induced autophagy and apoptosis were involved in NiCl2-induced nephrotoxicity was explored. The findings demonstrated that NAC relieved NiCl2-induced autophagy and reversed the activation of Akt/AMPK/mTOR pathway. Concurrently, the results indicated that NAC attenuated NiCl2-induced apoptosis, as evidenced by reduction of apoptotic cells and cleaved-caspase-3/− 8/− 9 together with cleaved-PARP protein levels. To sum up, our findings suggested that NiCl2-mediated renal injury was associated with oxidative stress-induced apoptosis and autophagy. This study provides new theoretical basis for excess Ni exposure nephrotoxic researches.

Copper (Cu), as a common chemical contaminant in environment, is known to be toxic at high concentrations. The current research demonstrates the effects of copper upon hepatocyte cell-cycle progression (CCP) in mice. Institute of cancer research (ICR) mice (n = 240) at an age of four weeks were divided randomly into groups treated with different doses of Cu (0, 4, 8, and 16 mg/kg) for 21 and 42 days. Results showed that high Cu exposure caused hepatocellular G0/G1 cell-cycle arrest (CCA) and reduced cell proportion in the G2/M phase. G0/G1 CCA occurred with down-regulation (p

In this study, experimental pathology, flow cytometry (FCM), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB) were used to evaluate the effects of sodium fluoride (NaF) on hepatocellular cell cycle progression in mice. A total of 240 ICR mice were divided equally into four groups; the experimental groups received 12, 24, or 48 mg/kg NaF intragastrically for 42 days, while the control group received distilled water. Doses of NaF above 12 mg/kg increased the percentage of cells in S phase (S-phase arrest), reduced percentages of cells in G0/G1 or G2/M phase, and activated the ATM-p53-p21 and ATR-Chk1-Cdc25A pathways. Activation of these pathways was characterized by up-regulation of ATM, p53, p21, ATR, and Chk1 mRNA and protein expression, and down-regulation of Cdc25A, cyclin E, cyclin A, CDK2, CDK4, and proliferating cell nuclear antigen (PCNA) mRNA and protein expression. These results indicate that NaF caused S-phase arrest by activating the ATM-p53-p21 and ATR-Chk1-Cdc25A pathways.

In this study, we investigated the roles of reactive oxygen species (ROS) and nuclear factor-κB (NF-κB) signaling in sodium fluoride-induced DNA damage and apoptosis in mouse splenocytes. Intragastric administration of 12, 24 or 48 mg/kg sodium fluoride resulted in a time- and dose-dependent increase in DNA fragmentation and apoptosis in mouse splenocytes on days 21 and 42. High ROS levels correlated with increased levels of phosphorylated IκB kinase and NF-κB p65 and decreased levels of inhibitory kappa B protein in splenocytes from mice treated with sodium fluoride. Moreover, splenocytes from sodium fluoride-treated mice showed high expression of pro-apoptotic proteins, including Bim, Bax, Bak, caspase-3 and poly ADP-ribose polymerase, and low expression of the anti-apoptotic proteins BcL-2 and BcL-xL. These results show that sodium fluoride induces apoptosis in mouse splenocytes by enhancing ROS-dependent NF-κB signaling.

// Hongrui Guo 1, * , Ping Kuang 1, * , Qin Luo 1, * , Hengmin Cui 1, 2 , Huidan Deng 1 , Huan Liu 1 , Yujiao Lu 1 , Jing Fang 1, 2 , Zhicai Zuo 1, 2 , Junliang Deng 1, 2 , Yinglun Li 1, 2 , Xun Wang 1, 2 and Ling Zhao 1, 2 1 College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Ya’an 625014, China * These authors have contributed equally to this work Correspondence to: Hengmin Cui, email: cui580420@sicau.edu.cn Keywords: NaF, blood, cellular immunity, humoral immunity, mice Received: March 21, 2017 Accepted: July 19, 2017 Published: August 10, 2017 ABSTRACT Exposure to high fluorine can cause toxicity in human and animals. Currently, there are no systematic studies on effects of high fluorine on blood cellular immunity and humoral immunity in mice. We evaluated the alterations of blood cellular immunity and humoral immunity in mice by using flow cytometry and ELISA. In the cellular immunity, we found that sodium fluoride (NaF) in excess of 12 mg/Kg resulted in a significant decrease in the percentages of CD3 + , CD3 + CD4 + , CD3 + CD8 + T lymphocytes in the peripheral blood. Meanwhile, serum T helper type 1 (Th1) cytokines including interleukin (IL)-2, interferon (IFN)-γ, tumor necrosis factor (TNF), and Th2 cytokines including IL-4, IL-6, IL-10, and Th17 cytokine (IL-17A) contents were decreased. In the humoral immunity, NaF reduced the peripheral blood percentages of CD19 + B lymphocytes and serum immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM). The above results show that NaF can reduce blood cellular and humoral immune function in mice, providing an excellent animal model for clinical studies on immunotoxicity-related fluorosis.

The current study was conducted to investigate the effect of sodium fluoride (NaF) on the oxidative stress and apoptosis as well as their relationship in the mouse liver by using methods of flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, biochemistry and experimental pathology. 240 four-week-old ICR mice were randomly divided into 4 groups and exposed to different concentration of NaF (0 mg/kg, 12 mg/kg, 24 mg/kg and 48 mg/kg) for a period of 42 days. The results showed that NaF caused oxidative stress and apoptosis. NaF-caused oxidative stress was accompanied by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreasing mRNA expression levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione-s-transferase (GST). NaF induced apoptosis via tumor necrosis factor recpter-1 (TNF-R1) signaling pathway, which was characterized by significantly increasing mRNA and protein expression levels of TNF-R1, Fas associated death domain (FADD), TNFR-associated death domain (TRADD), cysteine aspartate specific protease-8 (caspase-8) and cysteine aspartate specific protease-3 (caspase-3) in dose- and time-dependent manner. Oxidative stress is involved in the process of apoptotic occurrence, and can be triggered by promoting ROS production and reducing antioxidant function. NaF-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and increased serum alanine amino transferase (ALT), aspartic acid transferase (AST), alkaline phosphatase (AKP) activities and TBIL contents.

// Qin Luo 1 , Hengmin Cui 1,2 , Huidan Deng 1 , Ping Kuang 1 , Huan Liu 1 , Yujiao Lu 1 , Jing Fang 1,2 , Zhicai Zuo 1,2 , Junliang Deng 1,2 , Yinglun Li 1,2 , Xun Wang 1,2 and Ling Zhao 1,2 1 College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, China 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, China Correspondence to: Hengmin Cui, email: // Keywords : sodium fluoride, oxidative damage, lesion, dysfunction, kidney, Immunology and Microbiology Section, Immune response, Immunity Received : March 13, 2017 Accepted : April 11, 2017 Published : April 21, 2017 Abstract It has been reported that excessive intake of fluoride can induce renal lesions. However, its pathogenesis is still less understood. Therefore, this study was conducted to investigate oxidative damage and the relationships between the oxidative damage and renal lesions in fluoride-treated mice by using the methods of histopathology, biochemistry, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). A total of 240 ICR mice were randomly divided into four equal groups (sodium fluoride was given orally at the dose of 0, 12, 24 and 48 mg/kg body weight for 42 days, respectively). We found that fluoride in excess of 12 mg/kg induced renal oxidative damage, which was characterized by increasing the levels of reactive oxygen species (ROS) production and contents of malondialdehyde (MDA) and protein carbonyls (PC), and decreasing the abilities of anti-superoxide anion (ASA) and anti-hydroxyl radical (AHR), glutathione (GSH) content, as well as activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px). Concurrently, fluoride caused degeneration and necrosis of the tubular cells, renal tubular hyaline casts and glomeruli swelling, which were consistent with the alteration of renal function parameters including elevated contents of serum creatinine (Cr), serum uric acid (UA), blood urea nitrogen (BUN), and the activities of urinary N-acetyl-b-D-glucosaminidase (NAG), renal lactate dehydrogenase (LDH), and reduced activities of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and acid phosphatase (ACP) in the kidney. The above-mentioned results showed that fluoride in excess of 12 mg/kg induced renal oxidative damage, which then caused renal lesions and dysfunctions. These findings also clearly demonstrated that oxidative damage is one of the mechanisms of fluoride-induced renal lesions and dysfunctions.

The aim of the present study was to investigate the abilities of selenium to counteract the toxic damage of arsenic (As). Two hundred 1-day-old healthy male broilers were randomly divided into five groups and fed the following diets: control group (0.1 mg/kg As + 0.2 mg/kg Se), As group (3 mg/kg As + 0.2 mg/kg Se), As + Se group I (3 mg/kg As + 5 mg/kg Se), As + Se group II (3 mg/kg As + 10 mg/kg Se), and As + Se group III (3 mg/kg As + 15 mg/kg Se), respectively. The relative weight of the liver, hepatic protein content, GSH-Px levels, SOD activities, NO contents, iNOS and tNOS activities, and increased malondialdehyde contents, ALT and AST activities, and the apoptotic hepatocytes were analyzed. Adding 3 mg/kg arsenic to the diet caused the growth and development of chicken liver to be blocked, resulting in decrease of protein contents in liver tissue, decrease of SOD and GSH-Px activities, increase of MDA contents, decrease of NO contents, decrease of iNOS and TNOs activities, increase of ALT and AST activities, increase of apoptosis rates of liver cells. Compared to the 3-mg/kg arsenic group, adding 5 mg/kg and 10 mg/kg selenium, respectively, could repair the liver growth retardation and steatosis caused by arsenic, increase the protein contents in liver tissue, increase the activities of SOD and GSH-Px, reduce the contents of MDA, increase the contents of NO, enhance the activities of iNOS and TNOs, reduce the activities of ALT and AST, and reduce the rates of apoptosis of liver cells, in which the best effects are to add 10 mg/kg selenium. While 15 mg/kg of sodium selenite may induce progression of As-induced hepatic lesions, the results indicated that 5 and 10 mg/kg of sodium selenite supplied in the diet, through mechanisms of oxidative stress and apoptosis regulation, may ameliorate As-induced hepatic lesions in a dose-dependent manner.

Humidity sensors have attracted intense interest in various fields because of the importance of humidity detection. Different methods have been adopted to enhance sensing performances of humidity sensors, while it is challenging for researchers to avoid the invalidation of the sensors after being wet. Here, we, for the first time, introduce self-assembly MoS

Previously we demonstrated that fluoride increased acetylated-p53 (Ac-p53) in LS8 cells that are derived from mouse enamel organ epithelia and in rodent ameloblasts. However, how p53 is acetylated by fluoride and how the p53 upstream molecular pathway responds to fluoride is not well characterized. Here we demonstrate that fluoride activates histone acetyltransferases (HATs) including CBP, p300, PCAF and Tip60 to acetylate p53. HAT activity is regulated by post-translational modifications such as acetylation and phosphorylation. HAT proteins and their post-translational modifications (p300, Acetyl-p300, CBP, Acetyl-CBP, Tip60 and phospho-Tip60) were analyzed by Western blots. p53-HAT binding was detected by co-immunoprecipitation (co-IP). Cell growth inhibition was analyzed by MTT assays. LS8 cells were treated with NaF with/without HAT inhibitors MG149 (Tip60 inhibitor) and Anacardic Acid (AA; inhibits p300/CBP and PCAF). MG149 or AA was added 1 h prior to NaF treatment. Co-IP results showed that NaF increased p53-CBP binding and p53-PCAF binding. NaF increased active Acetyl-p300, Acetyl-CBP and phospho-Tip60 levels, suggesting that fluoride activates these HATs. Fluoride-induced phospho-Tip60 was decreased by MG149. MG149 or AA treatment reversed fluoride-induced cell growth inhibition at 24 h. MG149 or AA treatment decreased fluoride-induced p53 acetylation to inhibit caspase-3 cleavage, DNA damage marker γH2AX expression and cytochrome-c release into the cytosol. These results suggest that acetylation of p53 by HATs contributes, at least in part, to fluoride-induced toxicity in LS8 cells via cell growth inhibition, apoptosis, DNA damage and mitochondrial damage. Modulation of HAT activity may, therefore, be a potential therapeutic target to mitigate fluoride toxicity in ameloblasts.

Fluoride is known to affect the inflammatory process and autoregulation of immune responses, but the molecular mechanism by which fluoride causes innate immune injury remain largely unknown. Also, studies on sodium fluoride (NaF)-caused alteration of TLR signaling are still lacking. In the present study, we examined the effects of NaF on the mRNA and protein expression levels of TLR2/MyD88 signaling pathway molecules in the mouse spleen by using the methods of qRT-PCR and Western blotting. Consequently, we elucidated the mechanism underlying the effects of NaF on innate immunity. Two hundred and forty ICR mice were randomly divided into 4 groups with intragastric administration of distilled water in the control group and 12, 24, 48 mg/kg of NaF treatment in the experiment groups for 42 days. The findings revealed that NaF impaired splenic innate immunity in mice via inactivation of TLR2/MyD88 signaling pathway. NaF-inactivated TLR2/MyD88 signaling pathway was identified by prominently downregulated mRNA and protein expression levels of TLR2/MyD88, IRAK4, IRAK1, TRAF6, TAK1, MKK4/MKK7 and c-Jun, which ultimately altered the expression levels of IL-1β, IL-4, IL-6 and IL-8 to attenuate innate immunity.

// Ping Kuang 1, * , Huidan Deng 1, * , Hengmin Cui 1, 2 , Lian Chen 1 , Jing Fang 1, 2 , Zhicai Zuo 1, 2 , Junliang Deng 1, 2 , Xun Wang 1, 2 , Ling Zhao 1, 2 1 College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya’an 625014, China * These authors contributed equally to this work Correspondence to: Hengmin Cui, email: cui580420@sicau.edu.cn Keywords: NaF, growth index, T and B-cell, cytokine, cell cycle Received: November 07, 2016 Accepted: December 07, 2016 Published: December 16, 2016 ABSTRACT At present, very limited studies focus on the toxic effect of sodium fluoride (NaF) on splenic development of human and animals in vivo . This study was firstly designed to evaluate the toxic effects of NaF on the splenic development of mice in vivo by observing histopathological lesions, changes of splenic growth index (GI), T and B cells, immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents, cytokine protein expression levels, and cell cycle and cyclins/cdks protein expression levels using the methods of pathology, flow cytometry (FCM), western blot (WB), and enzyme-linked immunosorbent assay (ELISA). A total of 240 ICR mice were equally allocated into four groups with intragastric administration of distilled water in the control group and 12, 24, 48 mg/kg NaF solution in the experimental groups for 42 days. The results showed that NaF in 12 mg/kg and over caused the toxic effects on splenic development, which was characterized by reducing growth index and lymphocytes in the white and red pulp histopathologically, increasing cell percentages of the G0/G1 phase and decreasing cell percentages of the S phase, and reducing T cells and B cells as well as IgA, IgG, and IgM contents when compared with those in the control group. Concurrently, cytokines including interleukin-2 (IL-2), transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and cyclin (E/D and CDK2/4) protein expression levels were markedly decreased ( P < 0.05 or P < 0.01), and interleukin-10 (IL-10) protein expression levels were significantly increased ( P < 0.05 and P < 0.01) in the three NaF-treated groups. Toxic effects finally impaired the splenic cellular immunity and humoral immunity due to the reduction of T and B cell population and activity. Cell cycle arrest is the molecular basis of NaF-caused toxic effects on the splenic development.

The aim of this study was to find effects of Fusarium toxins on brain injury in mice. We evaluated the individual and combined effect of the Fusarium toxins zearalenone and deoxynivalenol on the mouse brain. We examined brain weight, protein, antioxidant indicators, and apoptosis. After 3 and 5days of treatment, increased levels of nitric oxide, total nitric oxide synthase, hydroxyl radical scavenging, and malondialdehyde were observed in the treatment groups. This was accompanied by reduced levels of brain protein, superoxide dismutase (apart from the low-dose zearalenone groups), glutathione, glutathione peroxidase activity, and percentage of apoptotic cells. By day 12, most of these indicators had returned to control group levels. The effects of zearalenone and deoxynivalenol were dose-dependent, and were synergistic in combination. Our results suggest that brain function is affected by zearalenone and deoxynivalenol.

// Ping Kuang 1, * , Huidan Deng 1, * , Hengmin Cui 1, 2 , Lian Chen 1 , Hongrui Guo 1 , Jing Fang 1, 2 , Zhicai Zuo 1, 2 , Junliang Deng 1, 2 , Xun Wang 1, 2 , Ling Zhao 1, 2 1 College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya’an 625014, China * These authors have contributed equally to this work Correspondence to: Hengmin Cui, email: cui580420@sicau.edu.cn Keywords: sodium fluoride, cytokine, cell cycle, splenic T lymphocytes, splenic B lymphocytes Received: May 01, 2016 Accepted: July 28, 2016 Published: August 16, 2016 ABSTRACT Fluoride-induced immunotoxicity has been documented in vivo, but limited reports have focused on the effects of fluoride on lymphocytes in vitro. Therefore, we have examined the suppressive effects of sodium fluoride on cultured splenic lymphocytes in mice. CD3+ T lymphocytes, CD19+ B lymphocytes, cytokines, and cell-cycle markers were analyzed through the use of a cell-counting kit, western blot, and flow cytometery. Splenic lymphocytes were isolated from 3-week-old male ICR mice and exposed to sodium fluoride (0, 100, 500, and 1000 μmol/L) for 24 h. The percentages of CD3 + , CD3 + CD4 + , CD3 + CD8 + T lymphocytes and CD19 + B lymphocytes were decreased (P

// Lian Chen 1 , Hengmin Cui 1, 2 , Jing Fang 1, 2 , Huidan Deng 1 , Ping Kuang 1 , Hongrui Guo 1 , Xun Wang 1, 2 , Ling Zhao 1, 2 1 College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya’an 625014, China Correspondence to: Hengmin Cui, email: cui580420@sicau.edu.cn Keywords: glutamine, apoptosis, BPTES, cisplatin, etoposide Received: April 19, 2016 Accepted: June 30, 2016 Published: July 13, 2016 ABSTRACT Glutamine provides cancer cells with the energy required to synthesize macromolecules. Methods which block glutamine metabolism in treatment of breast cancer inhibit oncogenic transformation and tumor growth. We investigated whether inhibiting glutamine metabolism produces effects that are synergistic with those produced by drugs which damage DNA in triple-negative breast cancer cells. HCC1937 and BT-549 breast cancer cells were co-treated with either cisplatin or etoposide in combination with BPTES (a specific inhibitor of glutaminase 1) or exposure to a glutamine-free medium, and the cell proliferation and cell apoptosis were measured by flow cytometry, immunoblotting studies, and CCK-8 assays. The results showed that both glutamine deprivation and BPTES pretreatments increased the toxic effects of cisplatin and etoposide on HCC1937 cells, as demonstrated by their reduced proliferation, increased expression of apoptosis-related proteins (cleaved-PARP, cleaved-caspase 9, and cleaved-caspase 3) and decreased Bcl-2/BAX ratio. However, in BT-549 cells, glutamine deprivation and BPTES treatment increased etoposide-induced apoptosis only when used with higher concentrations of etoposide, and the effect on cisplatin-induced apoptosis was minimal. These results suggest that the anti-cancer effects produced by a combined approach of inhibiting glutamine metabolism and administering common chemotherapeutic agents correlate with the tumor cell type and specific drugs being administered.

The aim of this study was to evaluate the effects of the Fusarium toxin zearalenone (ZEA) and/ or deoxynivalenol (DON) on the serum IL-1, IL-4, and C3 levels in mice. In our study, 360 healthy adult female mice were randomly assigned to 9 groups for a 12-day study. Mice of all groups were given a 4-day continuous intraperitoneal injection with different concentrations of ZEA alone, DON alone, and the mixture of ZEA and DON, individually. Blood samples were collected in days 0, 3, 5, 8, and 12 of the experiment. The experiment results showed that all of the experimental groups could cause the dysregulation of the IL-1, IL-4, and C3 levels, thus affecting the immunity of mice. The mixture groups, especially in the group with higher concentrations of ZEA and DON (Group D2Z2), showed more obvious effect on the dysregulation of the IL-1, IL-4, and C3 levels. There was a synergistic effect between DON and ZEA.

The aim of this study was to investigate the effects of dietary antimicrobial peptide (AMP) supplementation on the serum IgG, IgM, IgA, classical swine fever antibody (CSF-Ab), and total complement (CH50) levels in weaned piglets. Ninety weaned piglets were randomly allotted to five groups for 28-day study. Blood samples were collected at 32, 39, 46, and 53 days of age. The results showed that AMP as dietary additive increased the levels of IgG, IgM, IgA, CSF-Ab, CH50 among the whole experimental period, and the effects of AMP supplementation were dose-dependent. The study showed that supplementing weaned piglets diets with AMP enhanced the humoral immune responses of weaned piglets by improving the levels of classical swine fever virus antibody, CH50, and immunoglobulins. We suggest the dosage of AMP was 500 mg/kg.

Fluoride is widely distributed in the environment and often results in adverse health effects on animals and human beings. It has been proved that fluoride can induce inflammatory responses in vitro. However, very limited reports are focused on fluoride-induced inflammatory responses in vivo. In this study, mice were used to investigate sodium fluoride (NaF) induced renal inflammatory responses and the potential mechanism by using the methods of pathology, biochemistry, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A total of 240 ICR mice were randomly divided into four equal groups: the control group and three experimental groups (NaF was given orally at the dose of 0, 12, 24 and 48 mg/kg body weight for 42 days, respectively). The results showed that NaF in excess of 12 mg/kg induced the renal histopathological lesions, and inflammatory responses via the activation of nuclear factor-kappa B (NF-κB) signaling pathway and the reduction of anti-inflammatory cytokines expression. The activation of NF-κB signaling pathway was characterized by increasing the nitric oxide (NO) and prostaglandin E2 (PGE2) contents, inducible nitric oxide synthase (iNOS) activities and mRNA expression levels, and the mRNA and protein expression levels of cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-8 (IL-8) in three NaF-treated groups. Concurrently, the mRNA and protein expression levels of the anti-inflammatory cytokines including interleukin-4 (IL-4) and interleukin-10 (IL-10) were decreased in three experimental groups when compared with those in the control group.

Inflammation is a biological response of the immune system that can be triggered by a variety of factors, including pathogens, damaged cells and toxic compounds. These factors may induce acute and/or chronic inflammatory responses in the heart, pancreas, liver, kidney, lung, brain, intestinal tract and reproductive system, potentially leading to tissue damage or disease. Both infectious and non-infectious agents and cell damage activate inflammatory cells and trigger inflammatory signaling pathways, most commonly the NF-κB, MAPK, and JAK-STAT pathways. Here, we review inflammatory responses within organs, focusing on the etiology of inflammation, inflammatory response mechanisms, resolution of inflammation, and organ-specific inflammatory responses.

// Huidan Deng 1,* , Ping Kuang 1,* , Hengmin Cui 1,2 , Lian Chen 1 , Jing Fang 1,2 , Zhicai Zuo 1,2 , Junliang Deng 1,2 , Xun Wang 1,2 and Ling Zhao 1,2 1 College of Veterinary Medicine, Sichuan Agricultural University, Ya’an, China 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya’an, China * These authors have contributed equally to this work Correspondence to: Hengmin Cui, email: // Keywords : NaF; splenic lymphocytes; apoptosis; Bcl-2 family; caspases; Immunology and Microbiology Section; Immune response; Immunity Received : June 07, 2016 Accepted : September 12, 2016 Published : September 16, 2016 Abstract Though fluorine has been shown to induce apoptosis in immune organs in vivo , there has no report on fluoride-induced apoptosis in the cultured lymphocytes. Therefore, this study was conducted with objective of investigating apoptosis induced by sodium fluoride (NaF) and the mechanism behind that in the cultured splenic lymphocytes by flow cytometry, western blot and Hoechst 33258 staining. The splenic lymphocytes were isolated from 3 weeks old male ICR mice and exposed to NaF (0, 100, 200, and 400 μmol/L) in vitro for 24 and 48 h. When compared to control group, flow cytometry assay and Hoechst 33258 staining showed that NaF induced lymphocytes apoptosis, which was promoted by decrease of mitochondria transmembrane potential, up-regulation of Bax, Bak, Fas, FasL, caspase 9, caspase 8, caspase 7, caspase 6 and caspase 3 protein expression ( P < 0.05 or P

This study aimed to evaluate the effects of the Fusarium toxin zearalenone (ZEA) and deoxynivalenol (DON) on splenic antioxidant functions, IFN levels, and T-cell subsets in mice. Herein, 360 mice were assigned to nine groups for a 12-day study. Mice were administered an intraperitoneal injection for 4 consecutive days with different concentrations of ZEA alone, DON alone, or ZEA+DON. Spleen and blood samples were collected on days 0, 3, 5, 8, and 12. Mice in each of the experimental groups showed dysreglated splenic antioxidant functions, IFN levels, and T-cell subset frequencies, suggesting that the immune system had been affected. The ZEA+DON-treated groups, especially the group that received a higher concentration of ZEA+DON (Group D2Z2), showed more obvious effects on the dysregulation of splenic antioxidant functions, IFN levels, and T-cell subsets. This finding suggested that DON and ZEA exerted synergistic effects.

In this study, the in vitro effects of the treatment of concanavalin A (Con A)--stimulated splenic lymphocytes with DON were examined. Splenic lymphocytes isolated from chickens were stimulated with 12.5 μg/mL Con A and exposed to deoxynivalenol (DON) (0-50 μg/mL) for 48 h. The intracellular calcium concentration ([Ca(2+)]i), pH, calmodulin (CaM) mRNA levels, and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were detected. With the DON exposure concentrations increased, the [Ca(2+)]i and CaM mRNA levels gradually increased in a dose-dependent manner, and all the evaluated conconcentrations affected ATPase activity to the same extent. There were significant differences (P

// Hongrui Guo 1,* , Huidan Deng 1,* , Hengmin Cui 1,2 , Xi Peng 1,2 , Jing Fang 1,2 , Zhicai Zuo 1,2 , Junliang Deng 1,2 , Xun Wang 1,2 , Bangyuan Wu 1 and Kejie Chen 1 1 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya’an, Sichuan, China 2 College of Veterinary Medicine, Sichuan Agricultural University Ya’an, Sichuan, China * These authors have contributed equally to this work Correspondence to: Hengmin Cui, email: // Jing Fang, email: // Keywords : NiCl , inflammation; NF-κB, mRNA expression, kidney, Immunology section Received : July 11, 2015 Accepted : August 26, 2015 Published : September 21, 2015 Abstract Nickel (Ni) or Ni compounds target a number of organs and produce multiple toxic effects. Kidney is the major organ for Ni accumulation and excretion. There are no investigations on the Ni- or Ni compounds-induced renal inflammatory responses in human beings and animals at present. Therefore, we determined NiCl 2 -caused alteration of inflammatory mediators, and functional damage in the broiler’s kidney by the methods of biochemistry, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Dietary NiCl 2 in excess of 300 mg/kg caused the renal inflammatory responses that characterized by increasing mRNA expression levels of the pro-inflammatory mediators including tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-18 (IL-18) via the activation of nucleic factor κB (NF-κB), and decreasing mRNA expression levels of the anti-inflammatory mediators including interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-13 (IL-13). Concurrently, NiCl 2 caused degeneration, necrosis and apoptosis of the tubular cells, which was consistent with the alteration of renal function parameters including elevated alkaline phosphatase (AKP) activity, and reduced activities of sodium-potassium adenosine triphosphatase (Na + /K + -ATPase), calcium adenosine triphosphatase (Ca 2+ -ATPase), lactic dehydrogenase (LDH), succinate dehydrogenase (SDH) and acid phosphatase (ACP) in the kidney. The above-mentioned results present that the activation of NF-κB pathway and reduction of anti-inflammatory mediator expression are main mechanisms of NiCl2-caused renal inflammatory responses and that the renal function is decreased or impaired after NiCl2-treated.

We investigated the immunotoxicity and cytotoxicity of deoxynivalenol (DON), a mycotoxin, and the mechanism by which it induces apoptosis. Chicken splenic lymphocytes treated with 0-50μg/mL DON for 48h inhibited growth of splenic lymphocytes in a dose-dependent manner, as revealed by the Cell Counting Kit-8 (CCK-8) bioassay. Annexin V-fluorescein isothiocyanate staining indicated that the number of apoptotic and necrotic cells were significantly higher compared with the control (P

Deoxynivalenol (DON) immunotoxicity and its induction of cytokines and related genes in the splenic lymphocytes of chickens have not been completely elucidated. In the present study, we aimed to evaluate the effects of 48 h of different DON treatments (0 μg/mL, 0.2 μg/mL, 0.8 μg/mL, 3.2 μg/mL, 12.5 μg/mL, and 50 μg/mL) on the secretion and the mRNA expressions of some cytokine genes, such as interleukin-1beta (IL-1β), IL-1RI, IL-2, IL-4, IL-6, IL-10, IL-12β, and IFN-γ in chicken splenic lymphocytes. The concentrations of IL-1RI, IL-6, IL-10, and IFN-γ were increased with the DON concentrations increasing (P0.05 or P0.01). However, the concentrations of IL-1β, IL-2, IL-4, and IL-12β were decreased with the DON concentrations increasing (P0.05 or P0.01). Except IL-1β, the mRNA expressions of the other cytokines were up-regulated by DON. The highest mRNA expressions values of IL-1RI, IL-4, IL-10, IL-12β, and IFN-γ were at 50 μg/mL DON treatment groups (P0.05 or P0.01), while the highest mRNA expressions values of IL-2 and IL-6 were at 12.5 μg/mL DON treatment groups (P0.05 or P0.01). Our data revealed that the potent effects of DON in affecting the secretion and the mRNA expression of the related cytokines in chicken splenic lymphocytes in vitro.