mitfa deficiency promotes immune vigor and potentiates antitumor effects in zebrafish.

The mitfa gene is a well-known transcription factor associated with microphthalmia and is essential for early melanophore development. However, little is known about how mitfa affects the immune system. Here, we generated a novel mitfa knock-out zebrafish line using the CRISPR/Cas9 system. The mitfa-/- zebrafish exhibited reduced melanin levels compared to the nacre mutant. We investigated the impact on the immune system after exposure to Edwardsiella tarda and bifenazate in zebrafish larvae, and observed that the macrophage numbers were reduced in both treated groups. Remarkably, the expression levels of immune-related genes exhibited significant increases after bacterial challenge or bifenazate exposure in the mitfa-/- zebrafish, except for tlr4 and rela. Furthermore, we conducted xenograft experiments using mouse B16 melanoma cells. Notably, the cancer cells didn't show a high cell migration ratio, implying that the immune system was highly activated after the loss of mifta. Taken together, our findings suggest that mitfa-/- zebrafish serve as a valuable model for investigating the relationship between the immune system and melanocytes, providing new insights into the role of mitfa in immune responses.

Recent advances in micro (nano) plastics in the environment: Distribution, health risks, challenges and future prospects.

Environmental micro(nano)plastics have become a significant global pollution problem due to the widespread use of plastic products. In this review, we summarized the latest research advances on micro(nano)plastics in the environment, including their distribution, health risks, challenges, and future prospect. Micro(nano)plastics have been found in a variety of environmental media, such as the atmosphere, water bodies, sediment, and especially marine systems, even in remote places like Antarctica, mountain tops, and the deep sea. The accumulation of micro(nano)plastics in organisms or humans through ingestion or other passive ways poses a series of negative impacts on metabolism, immune function, and health. Moreover, due to their large specific surface area, micro(nano)plastics can also adsorb other pollutants, causing even more serious effects on animal and human health. Despite the significant health risks posed by micro(nano)plastics, there are limitations in the methods used to measure their dispersion in the environment and their potential health risks to organisms. Therefore, further research is needed to fully understand these risks and their impacts on the environment and human health. Taken together, the challenges of micro(nano)plastics analysis in the environment and organisms must be addressed, and future research prospects need to be identified. Governments and individuals must take action to reduce plastic waste and minimize the negative impact of micro(nano)plastics on the environment and human health.

Effects of dietary chlorogenic acid on ileal intestinal morphology, barrier function, immune factors and gut microbiota of broilers under high stocking density stress.

Aims: The purpose of this research was to assess the effect of chlorogenic acid (CGA) in the diet on ileac structure, barrier function, immunological state, and microbial profile of broiler chickens in a high stocking density (HD) environment. Methods: Four hundred and seventy-six male AA broiler chickens were randomly split into four groups, two with a normal stocking density (ND) of fourteen birds per m2 and two with a high stocking density of twenty-two birds per m2. Each of the treatments consisted of five replicates. One of the two ND and HD groups received the usual feed, while the other two were given at 1.5 g/kg CGA as part of their dietary regimen. Results: The ND CGA group showed a greater increase in villus height and villus height/crypt depth compared to the ND group at 35 and 42 days. The HD group experienced a greater elevation in villus height due to CGA supplementation than the HD group across days 28, 35, and 42. At day 42, the HD group saw a decline in OCLN and ZO-1 mRNA expression in the ileum, but CGA was able to restore them. The HD group experienced a greater rise in OCLN mRNA than the control HD group when supplemented with CGA. The expression of TNF-α, IL-1ß, and IL-6 in the ileum was higher in the HD group, and CGA supplementation enhanced this effect. The HD group experienced a greater rise in IL-10 mRNA expression than the control group following the administration of CGA. The HD group showed reduced alpha diversity and an increase in detrimental microbes such as Turicibacter and Shigella in the gut compared to the ND group, while the HD CGA group saw a reduction in Turicibacter, Shigella, and other harmful microbes. These findings reveal that HD stress suppressed the growth of ileac villi, decreased the expression of tight-junction genes, amplified the expression of inflammatory genes, and disturbed the gut microbiota, ultimately leading to increased intestinal permeability. Conclusion: We conclude that when chickens are given dietary CGA, the disruption of the ileac barrier and increased oxidative damage and inflammation due to HD stress are reduced, which increases ileac integrity and the presence of beneficial intestinal bacteria.

The influence of immune stress induced by Escherichia coli lipopolysaccharide on the pharmacokinetics of danofloxacin in broilers.

This study aimed to determine whether the challenge from Escherichia coli (E. coli) lipopolysaccharide (LPS) affects the pharmacokinetics of danofloxacin in broilers. Twenty 1-day-old Arbor Acres (AA) broilers were equally and randomly divided into 2 groups. When the chickens were 23, 25, 27, and 29 days old, E. coli LPS (1 mL; 0.5 mg/kg body weight [BW]) and sterile saline (1 mL) were intraperitoneally injected into the two groups. After the last injection, danofloxacin was given to all chickens by gavage at the dose of 5 mg/kg BW. Then serum and plasma samples at each time point were collected through the wing vein. Danofloxacin concentrations in plasma were detected through the high-performance liquid chromatography (HPLC) method and subjected to noncompartmental analysis using Phoenix software. The levels of chicken interleukin-1ß (IL-1ß) and corticosterone (CORT) in serum were measured by the Enzyme-linked immunosorbent assay (ELISA) kit. In addition, after the collection of plasma or serum samples, 7 chickens (31 days of age) in each group were killed to calculate the organ indices. Compared with the control group, the challenge of LPS significantly decreased the parameters of AUC0-∞, Cmax, and t1/2λz and increased the parameters of Tmax and λz. Additionally, in the LPS group, the absorption time of danofloxacin was prolonged; however, the elimination was accelerated, which resulted in reduced internal exposure.

Influence of Escherichia coli endotoxemia on danofloxacin pharmacokinetics in broilers following single oral administration.

As a fluoroquinolone antimicrobial agent, danofloxacin is mainly used to treat avian bacterial and mycoplasma infections. The pharmacokinetic characteristics of danofloxacin are usually explored in healthy animals, while those in endotoxemic broilers are still rare. This study aimed to investigate the pharmacokinetics of danofloxacin in endotoxemic broilers induced by Escherichia coli (E. coli) lipopolysaccharide (LPS) after single oral administration. Ten healthy 5-week-old Arbor Acres (AA) broilers with similar body weight (BW) were randomly and equally divided into LPS and control groups. The LPS group was intravenously injected with an LPS of E. coli O55: B5 at 2.5 mg/kg BW, and the control group was intravenously injected with the same volume of sterile saline. Danofloxacin was administered orally at a dose of 5 mg/kg BW immediately 1 h after the intravenous injection of LPS or sterile saline. Rectal temperature was measured at predetermined times points in all broilers, and plasma and serum samples were taken. The interleukin-6 (IL-6) levels in serum samples were detected by the enzyme-linked immunosorbent assay (ELISA) kits, and danofloxacin concentrations in plasma were detected through the high-performance liquid chromatography (HPLC) method and subjected to a compartmental analysis using Phoenix software. The LPS challenge led to biphasic adaptive changes in broiler body temperature and increased the levels of IL-6. Compared with the control group, LPS treatment significantly prolonged the time to the peak concentration (LPS: 8.75 ± 3.88 h; Control: 3.20 ± 2.20 h). However, there were no significant differences in the other pharmacokinetic parameters between both groups.

Disruption of Intestinal Homeostasis Through Altered Responses of the Microbial Community, Energy Metabolites, and Immune System in Zebrafish After Chronic Exposure to DEHP.

Di-(2-ethylhexyl) phthalate (DEHP) is ubiquitously reported in global water bodies and exhibits various environmental and human health risks. However, the effects of DEHP chronic exposure on the intestinal microbiota and associated host health concerns in aquatic species are still largely unexplored. In this study, chronic exposure to DEHP at environmental levels significantly increased the body weight, length, and body mass index (BMI), especially in male fish. The microbial community was disrupted with the relative abundance of phylum Firmicutes and genera diversity for Prevotella-7, Deefgea, PeM15, Halomonas, Akkermansia, Chitinibacter, and Roseomonas, which are significantly activated in zebrafish after exposure to DEHP. The height of the gut villus, the thickness of muscularis layer, and the number of goblet cells per villus were significantly decreased, as well as showed differences between female and male zebrafish. Further, the levels of energy-related metabolites in gut tissues were increased, compared to the control group. The expression levels of immune-related genes (interleukin 8, il-8, also referred to as cxcl8a), microbial defense-related genes (lysozyme, lyz, interleukin 10, and il-10), and obesity-related genes (aquaporin 8a, aqp8, mucin 2.1, muc2.1, fibroblast growth factor 2, fgf2, and proopiomelanocortin a, pomca) were significantly up-regulated in zebrafish, except the down-regulated expressions of toll-like receptor-5 (tlr-5) and interleukin 1ß (il-1ß) in the females and pomca in the males, respectively. Importantly, Spearman's correlation analyses revealed that the levels of metabolites and gene expressions in the gut were closely related to the dominant microbial genera, such as Aeromonas, Deefgea, Akkermansia, PeM15, Mycobacterium, and Rhodobacter. Taken together, chronic exposure to DEHP at environmental levels disturbed bacterial composition accompanied by the altered expressions of intestinal metabolites and the critical immune and intestinal function-related genes, which provided novel insights into DEHP effects on perturbation of gut microbiota and metabolic homeostasis in zebrafish.

Transcriptome and in silico approaches provide new insights into the mechanism of male reproductive toxicity induced by chronic exposure to DEHP.

Di-(2-ethylhexyl) phthalate (DEHP) can affect the male reproductive system in vertebrates, but the underlying molecular mechanism is still elusive. Therefore, in this study, we aimed to dig the in-depth mechanism of DEHP-induced reproductive toxicity on male zebrafish via testicular transcriptome using embryo exposed at the environmentally relevant concentration (ERC) of 100 µg/L for 111 days. Moreover, our results were further confirmed via in silico technique and bioassay experimental in vitro (cell lines) and in vivo (zebrafish). The results showed DEHP exposure could affect male spermatogenesis, altered gonad histology, and reduced egg fertilization rate. Transcriptome analysis identified 1879 significant differentially expressed genes enriched in the exposure group. Twenty-seven genes related to three pathways of reproduction behavior were further validated by qPCR. In silico molecular docking revealed that DEHP and its metabolism bind to the zebrafish progesterone receptor (Pgr), suggesting the potential disruption of DEHP to the normal Pgr signaling. To further validate it, a wild-type Pgr plasmid and its mutants on specific binding sites were constructed. The transfection and microinjection experiment demonstrated that these binding sites mutations of Pgr affected the expression levels of male reproductive toxicity. Taken together, our study provided new insight into the molecular mechanisms of male reproductive toxicity induced by DEHP, and Pgr may serve as an important target binding by DEHP pollution, which needs further study in the future.

A sheep in wolf's clothing: Elaphe xiphodonta sp. nov. (Squamata, Colubridae) and its possible mimicry to Protobothrops jerdonii.

Based on combined morphological and osteological characters and molecular phylogenetics, we describe a new species of the genus Elaphe that was discovered from the south slope of the Qinling Mountains, Shaanxi, China, namely Elaphe xiphodonta sp. nov. It is distinguished from the other congeners by a combination of the following characters: dorsal scales in 21-21-17 rows, the medial 11 rows keeled; 202-204 ventral scales, 67-68 subcaudals; two preoculars (including one subpreocular); two postoculars; two anterior temporals, three posterior temporals; reduced numbers of maxillary teeth (9+2) and dentary teeth (12); sharp cutting edges on the posterior or posterolateral surface of the rear maxillary teeth and dentary teeth; dorsal head yellow, three distinct markings on the head and neck; a distinct black labial spot present in supralabials; dorsum yellow, 46-49 complete (or incomplete) large black-edged reddish brown blotches on the body and 12-19 on the tail, two rows of smaller blotches on each ventrolateral side; ventral scales yellow with mottled irregular black blotches, a few irregular small red spots dispersed on the middle of the ventral. Based on molecular phylogenetic analyses, the new species forms the sister taxon to E. zoigeensis. The discovery of this new species increases the number of the recognized species in the genus Elaphe to 17.

Gut bacteria Vibrio sp. and Aeromonas sp. trigger the expression levels of proinflammatory cytokine: First evidence from the germ-free zebrafish.

Gut microbiota plays a central part in the regulation of multiple host metabolic pathways, such as homeostasis, immunostasis, mucosa permeability, and even brain development. Though, slight known about the function of an individual gut bacterium in zebrafish. In this study, germ-free (GF) and conventionally reared (CV) zebrafish models utilized for studying the role of gut bacteria Vibrio sp. and Aeromonas sp. After the analysis of gut microbial profile in zebrafish male and female at three-month age, Proteobacteria and Fusobacteria dominated the main composition of zebrafish intestinal microflora. However, the relative richness of them was different base on gender variance. Aeromonas sp. and Vibrio sp. belonging to Proteobacteria phylum of bacteria were isolated from zebrafish gut, and their potential capacities to trigger innate immunity were investigated. In gut microbiota absence, the expression levels of the innate immunity genes in the GF group were not significantly changed compared to the CV group. After exposure to Aeromonas sp. and Vibrio sp., the expression levels of myd88, TLRs-, and inflammation-related genes were increased in both GF and CV groups, except tlr2 and NLRs-related genes. However, the expression level of NF-κB and JNK/AP-1 pathway genes were all decreased after exposure to Aeromonas sp. and Vibrio sp. in both GF and CV groups. Interestingly, inflammation-related genes (tnfa, tnfb, and il1ß) were activated in the CV group, and there were not significantly changed in the GF group, indicating that other bacteria were indispensable for Aeromonas sp. or Vibrio sp. to activate the inflammation response. Taken together, this is the first study of gut bacteria Vibrio sp. and Aeromonas sp. prompting the innate immune response using the GF and CV zebrafish model.

Evidence of positively selected G6PD A- allele reduces risk of Plasmodium falciparum infection in African population on Bioko Island.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme that protects red blood cells from oxidative damage. Although G6PD-deficient alleles appear to confer a protective effect of malaria, the link with clinical protection against Plasmodium infection is conflicting. METHODS: A case-control study was conducted on Bioko Island, Equatorial Guinea and further genotyping analysis used to detect natural selection of the G6PD A- allele. RESULTS: Our results showed G6PD A- allele could significantly reduce the risk of Plasmodium falciparum infection in male individuals (adjusted odds ratio [AOR], 0.43; 95% confidence interval [CI], 0.20-0.93; p < .05) and homozygous female individuals (AOR, 0.11; 95% CI, 0.01-0.84; p < .05). Additionally, the parasite densities were significantly different in the individuals with different G6PD A- alleles and individual levels of G6PD enzyme activity. The pattern of linkage disequilibrium and results of the long-range haplotype test revealed a strong selective signature in the region encompassing the G6PD A- allele over the past 6,250 years. The network of inferred haplotypes suggested a single origin of the G6PD A- allele in Africans. CONCLUSION: Our findings demonstrate that glucose-6-phosphate dehydrogenase (G6PD) A- allele could reduce the risk of P. falciparum infection in the African population and indicate that malaria has a recent positive selection on G6PD A- allele.

Nanotoxicity of different sizes of graphene (G) and graphene oxide (GO) in vitro and in vivo.

Graphene family nanomaterials (GFNs) have attracted significant attention due to their unique characteristics and applications in the fields of biomedicine and nanotechnology. However, previous studies highlighted the in vitro and in vivo toxicity of GFNs with size and oxidation state differences are still elusive. Therefore, we prepared graphene (G) and graphene oxide (GO) of three different sizes (S-small, M-medium, and L-large), and characterized them using multiple surface-sensitive analytical techniques. In vitro assays using HEK 293T cells revealed that the small and large sizes of G and GO significantly reduced the cell viability and increased DNA damage, accompanying with activated reactive oxygen species (ROS) generation and induced various expressions of associated critical genetic markers. Moreover, the bacterial assays highlighted that G and GO caused strong acute toxicity on Tox2 bacteria. Effects of G were higher than GO and showed size dependent effect: L > M > S, while the medium size of GO induced mild genetic toxicity on RecA bacteria. In vivo assays revealed that exposure to G and GO caused the developmental toxicity, induced ROS generation, and activated related pathways (specifically GO) in zebrafish. Taken together, G showed stronger ability to decrease the survival rate and induce the acute toxicity, while GO showed obvious toxicity in terms of DNA damages, ROS generation, and abnormal gene expressions. Our findings highlighted that G and GO differentially induced toxicity based on their varying physical characteristics, especially sizes and oxidation state, and exposure concentrations and sensitivity of the employed in vitro and in vivo models. In short, this study provided deep insights on the negative effects of GFNs exposure.

Transcriptomic response and perturbation of toxicity pathways in zebrafish larvae after exposure to graphene quantum dots (GQDs).

Graphene quantum dots (GQDs) are widely used for biomedical applications. Previously, the low-level toxicity of GQDs in vivo and in vitro has been elucidated, but the underlying molecular mechanisms remained largely unknown. Here, we employed the Illumina high-throughput RNA-sequencing to explore the whole-transcriptome profiling of zebrafish larvae after exposure to GQDs. Comparative transcriptome analysis identified 2116 differentially expressed genes between GQDs exposed groups and control. Functional classification demonstrated that a large proportion of genes involved in acute inflammatory responses and detoxifying process were significantly up-regulated by GQDs. The inferred gene regulatory network suggested that activator protein 1 (AP-1) was the early-response transcription factor in the linkage of a cascade of downstream (pro-) inflammatory signals with the apoptosis signals. Moreover, hierarchical signaling threshold determined the high sensitivity of complement system in zebrafish when exposed to the sublethal dose of GQDs. Further, 35 candidate genes from various signaling pathways were further validated by qPCR after exposure to 25, 50, and 100 µg/mL of GQDs. Taken together, our study provided a valuable insight into the molecular mechanisms of potential bleeding risks and detoxifying processes in response to GQDs exposure, thereby establishing a mechanistic basis for the biosafety evaluation of GQDs.

Potential adverse outcome pathway (AOP) of silver nanoparticles mediated reproductive toxicity in zebrafish.

Recently, the augmented utilization of silver nanoparticles (AgNPs) resulted in increasingrates of its release to aquatic environment, which potentially caused adverse effects to aquatic organisms. Therefore, this study investigated - reproductive toxicity and associated potential adverse outcome pathway (AOP) in zebrafish after chronic exposure to AgNPs. To serve the purpose, three-month-old adult zebrafish were exposed to different concentrations (0, 10, 33 and 100 µg/L) of AgNPs for five weeks. Exposure to 33 and 100 µg/L of AgNPs significantly decreased the fecundity in female zebrafish, accompanied by increasing apoptotic cells in the ovarian and testicular tissue using TUNEL assay. Increasing tissue burdens of AgNPs and reactive oxygen species (ROS) production were also found in both ovary and testis after five-week exposure to AgNPs. To explore the mechanism of the apoptotic pathway, the transcription levels of various genes (bax, bcl-2, caspase-3, and caspase-9) associated with the mitochondrion-mediated apoptosis pathway were examined in zebrafish after exposure to AgNPs. The results showed that the expression patterns of all the investigated genes were altered to some extent. These findings demonstrated that AgNPs exposure caused oxidative stress, induced germ cells apoptosis via mitochondrial-dependent pathway, and ultimately impaired the reproduction in zebrafish.

Reproductive effects linked to DNA methylation in male zebrafish chronically exposed to environmentally relevant concentrations of di-(2-ethylhexyl) phthalate.

Di-(2-ethylhexyl) phthalate (DEHP) possesses the potential to interfere with the male reproductive endocrine system in mammals; however, its reproductive toxicity in male zebrafish and associated epigenetic studies have not been explored. In this study, three-month-old male zebrafish were exposed to environmentally relevant concentrations of DEHP (0, 10, 33 and 100 µg/L) for 3 months, and then the impact on the reproduction of males and the underlying mechanism were investigated. Histological testing showed that an exposure concentration of 100 µg/L DEHP significantly inhibited spermatogenesis, with an associated decline in capability to fertilize untreated oocytes. Electron microscopic examinations also revealed noticeable damage to the testicular ultrastructure at the 100 µg/L DEHP exposure level. In addition, exposure to 33 and 100 µg/L of DEHP resulted in a decline of circulating testosterone (T) and an increase in the level of 17ß-estradiol (E2), both of which were possibly derived from the downregulation of cyp17a1 and hsd17b3 genes and the upregulation of the cyp19a1a gene in the gonads. The DNA methylation statuses of these genes were altered within their promoter regions. A significant increase in global DNA methylation in both the male testes and their offspring larvae was observed at higher exposure concentration of DEHP. Our findings demonstrate that exposure to environmentally relevant concentrations of DEHP can damage the testes, disturbe the sex hormones production, and inhibite spermatogenesis, which ultimately impairs the reproduction of male zebrafish.

Generation and application of a novel transgenic zebrafish line Tg(cyp1a:mCherry) as an in vivo assay to sensitively monitor PAHs and TCDD in the environment.

The polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) are classified as human carcinogens, and can also cause serious health problems. To develop a convenient bio-monitoring tool for the detection of PAHs and TCDD in the environment, we generated a transgenic zebrafish line Tg(cyp1a:mCherry) with cyp1a promoter driving mCherry expression. Here, Tg(cyp1a:mCherry) embryos were treated with different concentrations of TCDD and five US EPA priority PAHs congeners. The results showed that the expressions of mCherry and endogenous cyp1a were consistent with the PAHs exposure concentrations and were largely induced by TCDD and ≥4-ring PAHs. Moreover, the sensitivity of Tg(cyp1a:mCherry) embryos was also evaluated through monitoring of the PAHs contamination in the water and soil samples. The elevated red fluorescent signals and cyp1a expression levels were observed in Tg(cyp1a:mCherry) zebrafish after exposure to water samples and soil organic extracts with higher concentrations of ≥4-ring PAHs. These results further strengthen our findings of concentration- and congener-dependent response of the newly established zebrafish. Taken together, the newly established zebrafish line will prove as a sensitive, efficient and convenient tool for monitoring PAHs and TCDD contamination in the environment.

Role of human DNA2 (hDNA2) as a potential target for cancer and other diseases: A systematic review.

DNA nuclease/helicase 2 (DNA2), a multi-functional protein protecting the high fidelity of genomic transmission, plays critical roles in DNA replication and repair processes. In the maturation of Okazaki fragments, DNA2 acts synergistically with other enzymes to cleave the DNA-RNA primer flaps via different pathways. DNA2 is also involved in the stability of mitochondrial DNA and the maintenance of telomeres. Moreover, DNA2 potentially participates in controlling the cell cycle by repairing the DNA replication faults at main checkpoints. In addition, previous evidences demonstrated that DNA2 also functions in the repair process of DNA damages, such as base excision repair (BER). Currently, large studies revealed the structures and functions of DNA2 in prokaryotes and unicellular eukaryotes, such as bacteria and yeast. However, the studies that highlighted the functions of human DNA2 (hDNA2) and the relationships with other multifunctional proteins are still elusive, and more precise investigations are immensely needed. Therefore, this review mainly encompasses the key functions of DNA2 in human cells with various aspects, especially focusing on the genome integrity, and also generalizes the recent insights to the mechanisms related to the occurrence of cancer and other diseases potentially linked to the mutations in DNA2.

Graphene oxide nanosheets induce DNA damage and activate the base excision repair (BER) signaling pathway both in vitro and in vivo.

Graphene oxide (GO) has widespread concerns in the fields of biological sciences and medical applications. Currently, studies have reported that excessive GO exposure can cause cellular DNA damage through reactive oxygen species (ROS) generation. However, DNA damage mediated response of the base excision repair (BER) pathway due to GO exposure is not elucidated yet. Therefore, we exposed HEK293T cells and zebrafish embryos to different concentrations of GO for 24 h, and transcriptional profiles of BER pathway genes, DNA damage, and cell viability were analyzed both in vitro and in vivo. Moreover, the deformation of HEK293T cells before and after GO exposure was also investigated using atomic force microscopy (AFM) to identify the physical changes occurred in the cells' structure. CCK-8 and Comet assay revealed the significant decrease in cell viability and increase in DNA damage in HEK293T cells at higher GO doses (25 and 50 µg/mL). Among the investigated genetic markers in HEK293T cells, BER pathway genes (APEX1, OGG1, CREB1, UNG) were significantly up-regulated upon exposure to higher GO dose (50 µg/mL), however, low exposure concentration (5, 25 µg/mL) failed to induce significant genetic induction except for CREB1 at 25 µg/mL. Additionally, the viscosity of HEK293T cells decreased upon GO exposure. In zebrafish, the results of up-regulated gene expressions (apex1, ogg1, polb, creb1) were consistent with those in the HEK293T cells. Taken all together, the exposure to elevated GO concentration could cause DNA damage to HEK293T cells and zebrafish embryos; BER pathway could be proposed as the possible inner response mechanism.

The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT) Axis in Zebrafish Larvae after Exposure to DEHP.

Di-(2-ethylhexyl) phthalate (DEHP) has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish (Danio rerio) embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 µg/L) from 2 to 168 hours post fertilization (hpf). Thyroid hormones (THs) levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT) axis were examined. The result of whole-body thyroxine (T4) and triiodothyronine (T3) indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone (tshß) and corticotrophin releasing hormone (crh) genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development (nkx2.1 and pax8) and thyroid synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) were also measured. The transcripts of nkx2.1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase (ugt1ab) and up-regulation of thyronine deiodinase (dio2) might change the THs levels. In addition, the transcript of transthyretin (ttr) was up-regulated, while the mRNA levels of thyroid hormone receptors (trα and trß) remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones.

Relationship between SERPING1 rs2511989 polymorphism and age-related macular degeneration risk: a meta-analysis.

PURPOSE: We conducted a meta-analysis aiming to evaluate the relationship between a common polymorphism (rs2511989 G>A) in the SERPING1 gene and the risk of age-related macular degeneration (AMD). METHODS: The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before November 1, 2013, without any language restrictions. A meta-analysis was conducted using STATA 12.0 software. We calculated a crude odds ratio (OR) with a 95% confidence interval (95% CI) to evaluate the relationships under five genetic models. RESULTS: Seven case-control studies with a total of 7,159 patients with AMD and 5,797 healthy subjects met the inclusion criteria. The results of our meta-analysis showed that the SERPING1 rs2511989 polymorphism might be correlated with an increased risk of AMD (G allele versus A allele: OR = 1.09, 95% CI = 1.03-1.15, p = 0.020; GG + GA versus AA: OR = 1.14, 95% CI = 1.03-1.26, p = 0.014; GG versus GA+AA: OR = 1.10, 95% CI = 1.02-1.19, p = 0.012; GG versus AA: OR = 1.20, 95% CI = 1.07-1.34, p = 0.002; respectively). Results of subgroup analysis by ethnicity revealed positive correlations between the SERPING1 rs2511989 polymorphism and risk of AMD among Caucasians under five genetic models (all p<0.05), but not among Asians (all p>0.05). CONCLUSIONS: The current meta-analysis shows that the SERPING1 rs2511989 polymorphism may have a positive effect on the risk of AMD, especially among Caucasians.

Zebrafish as a model system to study toxicology.

Monitoring and assessing the effects of contaminants in the aquatic eco-environment is critical in protecting human health and the environment. The zebrafish has been widely used as a prominent model organism in different fields because of its small size, low cost, diverse adaptability, short breeding cycle, high fecundity, and transparent embryos. Recent studies have demonstrated that zebrafish sensitivity can aid in monitoring environmental contaminants, especially with the application of transgenic technology in this area. The present review provides a brief overview of recent studies on wild-type and transgenic zebrafish as a model system to monitor toxic heavy metals, endocrine disruptors, and organic pollutants for toxicology. The authors address the new direction of developing high-throughput detection of genetically modified transparent zebrafish to open a new window for monitoring environmental pollutants.