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This study aimed to investigate the protective effect of sulforaphane (SFN) on liver injury induced by triphenyltin (TPT) in Cyprinus carpio (C. carpio). The fish (average weight of 56.9±0.4â¯g) were divided into 4 groups with four replicates: the control, TPT, SFN+TPT and SFN groups. Twenty fish were selected from each tank and cultured for 8 weeks. Then, serum and liver samples were collected for physiological, biochemical and metabolomic analyses. In the present study, TPT downregulated the expression of the lysozyme gene, upregulated HSP70 and Hsp90 gene expression, and decreased the activities of serum antioxidant enzymes (SOD, CAT, and GPX). However, dietary SFN alleviated oxidative stress, and prevented changes in immune genes. Metabolomic analysis revealed that TPT exposure changed key metabolites in the main phenylalanine, fatty acid and glycerophosphatide metabolic pathways, which are related to inflammation, oxidative stress and immunity and might also lead to an imbalance of liver energy and lipid metabolism. Dietary SFN promoted amino acid metabolism and increased metabolites related to immunity, anti-inflammation, antioxidation, and protein synthesis in liver of C. carpio. In summary, dietary SFN supplementation reversed TPT-induced decreases in immunity and oxidative stress and regulated amino acid metabolism, lipid metabolism, inflammation and immunity-related metabolic pathways.
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The purpose of this experiment was to study the mitigation effect of sulforaphane (SFN) on fish toxicological damage caused by triphenyltin (TPT) pollution. A total of 320 healthy fish (56.9 ± 0.4g) were randomly placed into four groups, each with four duplicates. The control group was fed the basal diet, the TPT group was exposed to 10 ng/L TPT on the basis of the control group, the SFN group was fed a diet supplemented with 10 mg/kg SFN, the SFN + TPT group was exposed to 10 ng/L TPT on the basis of the SFN group. Each tank had 20 fish and the breeding lasted for 8 weeks. The present study found that the antioxidant enzyme activity in the TPT group was significantly lower than that of the control group (P < 0.05). In addition, compared with the control group, the mRNA expression of pro-inflammatory factors (IL-6, TNF-α) were significantly induced, and the anti-inflammatory factor genes (IL-10, TGF) were significantly inhibited (P < 0.05) in TPT group. SFN relieved the changes of inflammatory factors caused by TPT, ameliorated oxidative stress, improved antioxidant enzyme (include SOD, CAT, GSH, GPx) activities (P < 0.05). 16s RNA analysis indicated that exposure to TPT caused changes in intestinal microflora. The results of the study showed that after exposure to TPT, some beneficial genera of bacteria in the gut of Rhizobiaceae, Bdellovibrio and Candidatus Alysiosphaera were decreased. The bacteria associated with intestinal inflammation including Propionibacterium, Rubrobacter, Anaerorhabdus_furcosa_group, Rikenellaceae and Eubacterium_brachy were upregulated. However, the SFN treatment group significantly down-regulated the above five inflammation-related bacteria. The above results indicated that TPT caused oxidative stress and inflammation in fish intestines, changed the intestinal microflora, and dietary SFN could improve antioxidant status, regulate inflammation and intestinal health. Therefore, SFN is a promising diet additive for improving fish damage caused by TPT contamination.
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Antioxidantes , Carpas , Animais , Antioxidantes/metabolismo , Carpas/metabolismo , Disbiose , Inflamação/induzido quimicamente , Inflamação/veterinária , Estresse OxidativoRESUMO
The present study was performed to determine the effects of Aeromonas hydrophila infection on intestinal -histopathology, innate immune response and changes in antioxidant capacity of blunt snout bream (Megalobrama amblycephala). A series of histopathological changes, innate immune enzyme activities, antioxidant enzyme activities, and the corresponding mRNA relative genes expressions in intestines were measured at 0, 1, 2, and 3 weeks post-treatment of Aeromonas hydrophila (1â107 CFU mL-1) infection. The results showed that Aeromonas hydrophila induced changes in intestinal morphology, including the decreased muscularis thickness, the proliferated goblet cells, and the atrophied intestine villi height. Moreover, the innate immune enzymes activities in serum such as acid phosphatase, alkaline phosphatase, lysozyme activities and immunoglobulin M were significantly reduced after infection at 1week, 2week and 3week. The contents of complement 3 and complement 4 were significantly decreased after infection as well. In addition, the antioxidant enzymes activities, including superoxide dismutase, catalase and glutathione peroxidase in the experimental groups were significantly decreased compared with the control group, whereas the content of malondialdehyde was significantly increased after infection at 1week, 2week and 3week. Furthermore, the mRNA relative expressions of the inflammatory cytokines such as tumor necrosis factor-α, interleukins-1ß, interferon-γ, and interleukins-6 were significantly increased after infection with Aeromonas hydrophila. The TJ-related gene expressions in the intestine of zonula occluden-1, occludin, occludin-1, occludin-2 were significantly reduced throughout the infection period. The mRNA relative expressions of signal transducers and activators of transcription 4 and janus kinase-3 in the intestine were significantly ascended compared with the non-infected group. Overall, the results elucidated that the intestine tissue injury and innate immune response reduction, as well as antioxidant capacity attenuation were occurred against Aeromonas hydrophila infection of the blunt snout bream.
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Cyprinidae , Cipriniformes , Infecções por Bactérias Gram-Negativas , Aeromonas hydrophila/fisiologia , Animais , Antioxidantes/metabolismo , Cyprinidae/genética , Cipriniformes/genética , Suplementos Nutricionais , Proteínas de Peixes/metabolismo , Imunidade Inata , Interleucinas/metabolismo , Intestinos , Ocludina/metabolismo , Ocludina/farmacologia , RNA Mensageiro/metabolismoRESUMO
Benzo[a]pyrene (BaP), a model compound of polycyclic aromatic hydrocarbon known to impair reproductive functions of vertebrates, while the data is scarce in marine invertebrates. To investigate the toxic effects of BaP on invertebrates reproduction, we exposed male scallop (Chlamys farreri) to BaP (0, 0.38 and 3.8⯵g/L) throughout three stages of reproductive cycle (early gametogenesis stage, late gametogenesis stage and ripe stage). The results demonstrated that BaP decreased the gonadosomatic index and mature sperms counts in a dose-dependent manner. Significant changes in sex hormones contents and increased 17ß-estradiol/testosterone ratio suggested that BaP produced the estrogenic endocrine effects in male scallops. In support of this view, we confirmed that BaP significantly altered transcripts of genes along the upstream PKA and PKC mediated signaling pathway like fshr, lhcgr, adcy, PKA, PKC, PLC and NR5A2. Subsequently, the expressions of genes encoding downstream steroidogenic enzymes (e.g., 3ß-HSD, CYP17 and 17ß-HSD) were impacted, which corresponded well with hormonal alterations. In addition, BaP suppressed transcriptions of spermatogenesis-related genes, including ccnd2, SCP3, NRF1 and AQP9. Due to different functional demands, these transcript profiles involved in spermatogenesis exhibited a stage-specific expression pattern. Furthermore, histopathological analysis determined that BaP significantly inhibited testicular development and maturation in male scallops. Overall, the present findings indicated that, playing as an estrogenic-like chemical, BaP could disrupt the steroidogenesis pathway, impair spermatogenesis and caused histological damages, thereby inducing reproductive toxicities with dose- and stage-specific effects in male scallops. And the adverse outcomes might threaten the stability of bivalve populations and destroy the function of marine ecosystems in the long term.
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Benzo(a)pireno , Pectinidae , Animais , Benzo(a)pireno/toxicidade , Ecossistema , Masculino , Pectinidae/genética , Reprodução , EspermatogêneseRESUMO
This study aimed to investigate the detoxification metabolism responses in scallop Chlamys farreri exposed to phenanthrene (PHE), chrysene (CHR), benzo[a]pyrene (B[a]P) and PHE + CHR + B[a]P for 15 days under laboratory conditions. The mRNA expression levels of AhR signaling pathway (AhR, HSP90, XAP2 and ARNT), detoxification system (phase I: CYP1A1 and CYP1B1; phase II: SULTs, UGT and GSTs) and ATP-binding cassette transporters (phase 0: ABCB1 and phase III: ABCC1, ABCG2) in digestive glands of scallops exposed to PHE (0.7, 2.1 µg/L), CHR (0.7, 2.1 µg/L), B[a]P (0.7, 2.1 µg/L), and PHE + CHR + B[a]P (0.7 + 0.7 +0.7, 2.1 + 2.1 + 2.1 µg/L) were detected. In present study, key genes (AhR, HSP90, XAP2 and ARNT) of the AhR signaling pathway can be significantly induced by pollutants, suggesting that the AhR/ARNT signaling pathway plays a role directly or indirectly. AhR, HSP90 and ARNT reached the maximum value on day 6, which can be preliminarily understood as the synchronization of their functions. Besides, the results also indicated that different genes had specific response to different pollution exposure. CYP1B1, GST-2, GST-omega and GST-microsomal could be potional indexes to PHE, ARNT, GST-sigma 2 and GST-3 were sensitive to CHR exposure, HSP90, GST-theta and ABCG2 were considered as potional indexes to BaP while CYP1A1 and UGT were possible to be indexes for monitoring the mix exposure of these three PAHs. These findings in C. farreri suggested that phase II detoxification metabolic enzymes isoforms played an essential role in detoxification mechanisms and mRNA expression levels of specific SULTs, UGTs and GSTs were potentially to be ideal indexes in PAHs pollution research. In summary, this study provides more valuable information for the risk assessments of different rings of PAHs.
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Pectinidae , Poluentes Químicos da Água , Animais , Benzo(a)pireno/toxicidade , Desintoxicação Metabólica Fase II , Isoformas de Proteínas/genética , Transdução de Sinais , Poluentes Químicos da Água/toxicidadeRESUMO
In this study, we cloned the full-length cDNA of the Kelch-like ECH-associated protein 1 (Keap1) from the scallops Chlamys farreri (C. farreri). Sequences alignment and phylogenetic analysis showed that CfKeap1 was highly specific in the scallops, and the amino acid sequence identity value is closer to that in zebrafish Keap1b and Nothobranchius furzeri Keap1b than Keap1a. The highest transcription level of CfKeap1 expression was detected in the digestive glands. The gene expressions of CfKeap1, NF-E2-related nuclear factor 2 (Nrf2), Superoxide Dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPx) in digestive glands were evaluated by quantitative real-time PCR (qRT-PCR) after being exposed to benzo(a)pyrene (BaP) (0.25, 1and 4⯵g/L) for 15 days, which indicated that the activation of Nrf2 and Keap1 expression can be significantly induced under BaP exposure. RNA interference (RNAi) experiments were conducted to examine the expression profiles of CfKeap1, Nrf2, antioxidant genes (Cu/Zn-SOD, CAT and GPx), mitogen-activated protein kinase (MAPKs) and protein kinase C (PKC) signaling pathways key genes in digestive glands and gills when exposed to BaP. Results showed that the mRNA level of CfKeap1 was significantly decreased by 60.69% and59.485%. The changes of CfKeap1 and Nrf2 suggested that the enhancement of Keap1 expression stimulating Nrf2 degradation. Furthermore, the expression of antioxidant genes were consistent with the Nrf2 gene, which suggesting that Nrf2-Keap1 signaling pathway is required for the induction of antioxidant genes. Besides, the changes of PKC, c-Jun N-terminal kinase (JNK) and p38 genes expression suggested that PKC and MAPKs signaling pathways played a synergistic role with Nrf2-Keap1 signaling pathway in the anti-oxidative defense system of bivalve molluscs. In conclusion, these data demonstrated that Keap1 can sense nucleophilic or oxidative stress factors to regulate the Nrf2 signaling pathway together with Cul3-based E3 Ubiquitin Ligase (E3), and the Nrf2-Keap1 signaling pathway played an important role in modulating gene expression of antioxidant enzymes in bivalve mollusks.
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Benzo(a)pireno/efeitos adversos , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/imunologia , Pectinidae/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Sequência de Aminoácidos , Animais , Perfilação da Expressão Gênica , Proteína 1 Associada a ECH Semelhante a Kelch/química , Fator 2 Relacionado a NF-E2/química , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/imunologia , Pectinidae/genética , Pectinidae/imunologia , Filogenia , Alinhamento de Sequência , Transdução de SinaisRESUMO
BACKGROUND: Native T1 mapping is an emerging cardiac magnetic resonance technique for quantitative evaluation of cardiomyopathies. This study aimed to investigate the usefulness of native T1 mapping in characterizing myocardial abnormalities in left ventricular non-compaction (LVNC) by comparing it with late gadolinium enhancement (LGE). METHODSâANDâRESULTS: The study group of 31 LVNC patients and 8 normal controls underwent cardiovascular magnetic resonance to acquire the native T1 maps and LGE images. Of the 31 LVNC patients, 14 had LGE. The mean native T1 value of the normal controls, LGE(-) and LGE(+) patients was 1,098.8±40.8 ms, 1140.6±32.8 ms, and 1181.4±53.7 ms, respectively. Significant differences were found in native T1 between any 2 groups (F=9.74, P<0.001). In discriminating the presence of LGE in LVNC patients, the odds ratio and corresponding 95% confidence interval (CI) of native T1 were, respectively, 2.966 (95% CI: 1.123-7.835, P=0.028) and 4.348 (95% CI: 1.155-16.363, P=0.030) before and after adjusting for confounding factors with an increment of 1 standard deviation. CONCLUSIONS: The finding that LGE(-) patients had elevated native T1 compared with normal controls suggested native T1 mapping can be used earlier than LGE imaging to detect myocardial fibrosis in LVNC patients. Furthermore, higher native T1 values in LGE(+) patients than in the LGE(-) group suggested native T1 mapping is more sensitive than LGE imaging for identifying myocardial fibrosis in LVNC patients. (Circ J 2016; 80: 1210-1216).
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Gadolínio , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Função Ventricular Esquerda , Estudos de Casos e Controles , Estudos de Coortes , Fibrose/diagnóstico por imagem , Humanos , Fatores de TempoRESUMO
BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with premature atherosclerosis. However, the associated mechanism remains unknown. This study investigates the expression of adenosine triphosphate (ATP)-binding cassette transporter protein A1 (ABCA1) and cellular cholesterol efflux in cultured macrophages from OSAHS patients. METHODS: Of the 18 subjects enrolled in this study, six subjects with apnea-hypopnea index (AHI) <5 were placed into the control group, and 12 subjects with AHI ≥5 were placed into the OSAHS group. Peripheral blood mononuclear cells (PBMCs) from each subject were isolated, purified, cultured, and differentiated into macrophages in vitro. ABCA1 mRNA and protein expression were evaluated by reverse transcription PCR and Western Blot, respectively. Both ABCA1-mediated and autologous serum induced cholesterol efflux were measured by isotopic cholesterol efflux assays. RESULTS: The levels of AHI and high sensitivity C-reactive protein (hsCRP) were significantly higher in the OSAHS group than in the control group. ABCA1 mRNA and protein expressions in PBMCs-derived macrophages were significantly reduced in patients with OSAHS compared to that in controls (p < 0.05). Both ABCA1-mediated and autologous serum-induced cholesterol efflux were significantly lower in the OSAHS group than that in the control group (p = 0.033 and p = 0.01, respectively). Pearson's correlation analysis revealed a negative correlation between AHI and the mRNA (r = -0.7726, p = 0.0007) and protein (r = -0.8112, p = 0.0044) expression of ABCA1, a positive correlation between ABCA1-mediated cholesterol efflux and the minimum oxygen saturation (r = 0.7954, p < 0.0001), and a negative correlation between AHI and autologous serum induced cholesterol efflux (r = -0.7756, p = 0.0002). CONCLUSION: ABCA1 expression and cellular cholesterol efflux in macrophages were significantly decreased in OSAHS patients, which closely correlated with the severity of disease. Our findings provide meaningful insights into the mechanism of atherogenesis in OSAHS patients.
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Transportador 1 de Cassete de Ligação de ATP/genética , Aterosclerose/genética , Aterosclerose/fisiopatologia , Colesterol/metabolismo , Macrófagos/fisiologia , Apneia Obstrutiva do Sono/genética , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Estudos de Casos e Controles , Células Cultivadas , Feminino , Regulação da Expressão Gênica/genética , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Valores de Referência , Estatística como AssuntoRESUMO
Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH) with the most carcinogenic effects of all the PAHs, has multiple toxic effects on marine bivalves. We investigated the interference mechanism of B[a]P on food metabolism (sugars, proteins, and sugars), and on reproductive endocrine and ovarian development in female scallops (Chlamys farreri). Scallops were exposed to different concentrations of B[a]P concentrations of 0, 0.38, 3.8, and 38 µg/L throughout gonadal development. Total cholesterol and triglyceride contents in the digestive glands were increased, and their synthesis genes were upregulated. The plasma glucose contents decreased with the inhibition of glycogen synthesis genes and the induction of glycolysis genes in the digestive gland. The results showed that B[a]P had endocrine-disrupting effects on scallops, that it negatively affected genes related to ovarian cell proliferation, sex differentiation, and egg development, and that it caused damage to ovarian tissue. Our findings supplement the information on B[a]P disruption in gonadal development of marine bivalves. Environ Toxicol Chem 2024;43:748-761. © 2023 SETAC.
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Benzo(a)pireno , Pectinidae , Animais , Feminino , Benzo(a)pireno/toxicidade , Benzo(a)pireno/metabolismo , Diferenciação Sexual , Pectinidae/genética , Pectinidae/metabolismo , Alimentos Marinhos , Açúcares/farmacologiaRESUMO
Uterine serous carcinoma (USC) is a biologically aggressive subtype of endometrial cancer. Anti-human epidermal growth factor receptor 2 (HER2) therapy has demonstrated its promising effects on HER2-positive USC. However, data on prognostic relevance and immune microenvironment are limited in HER2-positive USC. This study aimed to determine the clinicopathologic features, prognosis, and the immune microenvironment trait in HER2 status in USC. We applied immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and multi-color immunofluorescence to investigate HER2 expression and amplification, PD-L1 expression, and tumor infiltration lymphocytes (TIL) in 77 USC (61 pure and 16 mixed-type USC). HER2 IHC 1 + , 2 + , and 3 + were found in 26, 18, and 10 USC, respectively. HER2 staining frequently had an incomplete membrane (basolateral or "U"-shaped) pattern. Twenty-three cases (23/54, 42.6%) showed an intra-tumor heterogeneous staining. HER2 amplification was present in 16/77 (20.8%) USC. HER2 amplification was significantly associated with deep myometrial invasion (> 1/2), and increased intra-epithelial and stromal density of CD20 + or CD8 + TIL (all P < 0.05), but not with USC subtypes (pure versus mixed-type), PD-L1 expression, CD4 + TIL, CD68 + histiocytes, or the CD4 + /CD8 + ratio (p > 0.05). HER2 amplification was associated with poor overall and progression-free survival in USC, but lost the prognostic significance on multivariate analysis. We concluded that HER2 amplified USC had adverse clinical outcomes, but showed the potential active immune microenvironment. Our findings raised the possibility of the combined anti-HER2 and immunotherapy for HER2-positive USC in the future.
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Aeromonas hydrophila (A. hydrophila) is one of the most pathogenic disease-causing bacteria, and causes massive death of animals including fish. Thus, strategies are being sought to ameliorate the impact of A. hydrophila. In this study, we have evaluated the ameliorative potential of dietary Lactobacillus delbrueckii (L. delbrueckii). The fishes were divided into the control group, an A. hydrophila group (A. hydrophila), and an L. delbrueckii group (A. hydrophila + 1*107 CFU/g L. delbrueckii). The results showed that A. hydrophila increased reactive oxygen species (ROS) content. However, dietary supplementation with L. delbrueckii prevented oxidative damage caused by elevated levels of ROS. The toxic effects of A. hydrophila on superoxide dismutase (SOD) activity, glutathione-S-transferase (GST), glutathione peroxidase (GPx), and glutathione reductase (GR), along with the levels of glutathione (GSH), were mitigated by dietary L. delbrueckii (P < 0.05). Also, Dietary L. delbrueckii induced the expression of antioxidant-related genes (sod, cat, gpx, gst, NF-E2-related factor 2 (nrf2), Kelch-like-ECH-and associated protein 1a (keap1a)) in the intestine of fish (P < 0.05). Furthermore, L. delbrueckii increased A. hydrophila-induced lysozyme, ACP, C3, and C4 decline. The mRNA expression levels of interleukin 1ß (il-1ß), interleukin 8 (il-8), tumour necrosis factor α (tnf-α), and nuclear transcription factor-κB p65 (nf-κb p65) were significantly elevated by A. hydrophila. In contrast, the relative mRNA expression levels of inhibitor factor κBα (iκbα) in the intestine were decreased by A. hydrophila (P < 0.05). However, L. delbrueckii prevented A. hydrophila-induced the relative mRNA expression changes. These present results demonstrate that dietary L. delbrueckii alleviated A. hydrophila-induced oxidative stress, immunosuppression, inflammation, and apoptosis in common Cyprinus carpio.
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BACKGROUND: Cervical cancer is characterized by a complex immunosuppressive tumor microenvironment (TME). Disulfidptosis is a recently identified form of programmed cell death that has emerged as a crucial factor in tumorigenesis. However, the research on the specific involvement of disulfidptosis within the TME is still in its early stages. METHODS: Under glucose starvation, SiHa and HeLa cells underwent experiments employing diverse cell death inhibitors and SLC7A11 knockdown to observe their impact on cell survival. TCGA-CESC cohort was subjected to consensus clustering for disulfidptosis-related clusters. Prognosis, function, immune infiltration, and differentially expressed genes (DEGs) evaluations among clusters were compared. A prognostic model based on DEGs and disulfidptosis regulator genes (DRGs) was constructed and internally and externally validated. The correlation between YWHAG and clinicopathological characteristics in cervical cancer patients was investigated at both the mRNA and protein levels. Proliferation and migration assays were performed to uncover the roles of YWHAG in cervical cancer. RESULTS: Experimental validation confirmed disulfidptosis in cervical cancer cell lines. Cervical cancer patients were classified into three clusters based on DRGs, showing notably improved prognosis and increased immune infiltration in cluster B. The developed disulfidptosis-related prognostic model effectively stratified patients into high- and low-risk groups. Low-risk patients exhibited more favorable responses to immunotherapy and improved overall prognosis. Additionally, YWHAG, recognized as a tumor-promoting gene, demonstrated active roles in enhancing the growth, migration, and invasion of cervical cancer cells. CONCLUSION: Our research proposed a prognostic model for cervical cancer, probably contributing to tumor microenvironment traits and more potent immunotherapy strategy exploration.
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The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.
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Ammonia is one of the most important aquatic environmental factors, which is of great concern. In order to evaluate the effect of ammonia on guppy (Poecilia reticulate), fish were exposed to increased concentrations (0, 12.50, 25.00, 41.67, 62.50 mg/L) of ammonia for 48 h. After exposure, we measured the anxiety behavior, antioxidant enzymes and pro-inflammation genes (TNF-α, IL-1ß and IL-6) of guppy. The results showed that ammonia stress induced fish anxiety, which was manifested by the increased latency to enter the upper half and decreased time spent in upper half compared with control fish. The guppy showed oxidative stress after 48 h of ammonia stress as evidenced by decreases in the activities of antioxidant enzymes and an increase in lipid hydroperoxide content. With prolonged ammonia stress, the expressions of HSP70, HSP90, TNF-α, IL-1ß and IL-6 mRNA at first had an increasing trend, and then decreased, all of which were significantly higher than the control levels at 12 h and 24 h after ammonia stress (P < 0.05). Ammonia significantly upregulated these genes mRNA levels after 48 h exposure, suggesting that heat shock proteins and innate immune system may try to protect cells from oxidative stress induced by ammonia stress. Our study showed that higher ammonia exposure induced oxidative stress in exposed fish, since inhibition of antioxidant enzymes activity and increases in lipid peroxidation, and inflammation occurred. Furthermore, the results will be helpful to understand the mechanism of ammonia toxicity in guppys.
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Antioxidantes , Poecilia , Animais , Antioxidantes/metabolismo , Poecilia/metabolismo , Amônia/toxicidade , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Estresse Oxidativo , Inflamação/induzido quimicamente , Ansiedade/induzido quimicamente , RNA Mensageiro/metabolismoRESUMO
As one of the most carcinogenic persistent organic pollutants (POPs), benzo[a]pyrene (B [a]P) brings high toxicity to marine bivalves. Digestive gland is the most important metabolism-related organ of aquatic animals. This study conducted the digestive gland transcriptome of Chlamys farreri under B[a]P treatment at reproductive stages. And the reproductive-stage dependence metabolism-DNA repair-apoptosis process of scallops under 0, 0.04, 0.4 and 4 µg/L B[a]P was studied by qRT-PCR. The results demonstrated that the detoxification metabolism was disturbed after ovulation except for CYP3A4. In antioxidant system, antioxidant enzyme CAT and GPX, and GGT1 (one of the non-enzymatic antioxidants synthesis gene) continuously served the function of antioxidant defense. Three types of DNA repair were activated under B[a]P stress, however, DNA strand breaks were still serious. B[a]P exposure weakened death receptor pathway as well as enhanced mitochondrial pathway, surprisingly suppressing apoptosis in scallops. In addition, ten indicators were screened by Spearman correlation analysis. This study will provide sound theoretical basis for bivalve toxicology and contribute to the biomonitoring of marine POPs pollution.
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Benzo(a)pireno , Pectinidae , Feminino , Animais , Benzo(a)pireno/toxicidade , Antioxidantes , Pectinidae/genética , Dano ao DNA , ApoptoseRESUMO
This study was conducted to elucidate the effects of FOS that alleviate Aeromonas hydrophila-induced intestinal damage. The results showed that A. hydrophila disrupted the intestinal structure and increased intestinal permeability, causing abnormalities in mucosal pathology. Additionally, A. hydrophila induced an imbalance in the intestinal flora and disturbed its stability. Dietary FOS ameliorated the injury to the intestinal structure of fish, but also in part improved the condition of the intestinal tight junction complex. Transcriptomic analysis showed that 120 genes were up-regulated and 320 genes were down-regulated. The intestinal immune network for the IgA production signalling pathway was enriched following A. hydrophila infection, and the change in the FOS group was mainly in the Tight junction signalling pathway. Similarly, dietary FOS reduced the disruption of the intestinal microbiota induced by A. hydrophila and improved the intestinal microbiota's stability; FOS was also partially implicated in the upregulation of Tight junction and Adhesion junction pathways by transcriptomic analysis. After further analysis, it was found that fish fed FOS had upregulated expression of genes related to apoptosis, antigen presentation, and the T-cell-mediated immune response in the intestine compared with those in the A. hydrophila group, which may be related to changes in the intestinal microbiome.
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Carpas , Cipriniformes , Doenças dos Peixes , Animais , RNA Ribossômico 16S , Aeromonas hydrophila , Intestinos , Perfilação da Expressão Gênica , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/genéticaRESUMO
Lipids are the main energy support during gametogenesis. Digestive gland is the key organ of aquatic animal metabolism for storing nutrition and supplying energy. It participates in a variety of life activities (such as growth, digestion, immunity, and reproduction). Nutrients stored in digestive glands, especially lipids, provide energy for reproductive behaviors such as gametogenesis and ovulation. A large number of studies have confirmed the accumulation of lipids from digestive gland to gonad during gametogenesis. At present, the research on the interference mechanism of persistent organic pollutants (POPs) on lipid metabolism of aquatic animals and the adaptive response of aquatic animals to POPs stress focus on biochemical levels or a few genes. The potential molecular mechanism of lipid metabolism interference needs to be further studied. In addition, as an important stage of aquatic animals, the reproductive period is a vigorous period of lipid metabolism. However, at present, there is no report on the molecular mechanism of POPs interfering with the lipid metabolism of the digestive gland in the reproductive process of aquatic animals. In this study, female scallop C. farreri was cultured in natural seawater and exposed to 4 µg/L B[a]P in seawater. Transcriptome analysis of digestive glands at multiple stages (proliferative stage, growth stage, mature stage and spawn stage) was performed, and iPath pathway analysis was used to analyze lipid metabolism pathways and differential genes. The interference mechanism of lipid metabolism in bivalves during reproductive period was revealed. This study will provide valuable genomic information on the role of digestive glands in lipid metabolism and reproduction of C. farreri, and will contribute to further functional genomics of bivalves and other closely related species.
Assuntos
Metabolismo dos Lipídeos , Pectinidae , Animais , Benzo(a)pireno/metabolismo , Feminino , Perfilação da Expressão Gênica , ReproduçãoRESUMO
Reproductive toxicity induced by benzo[a]pyrene (B[a]P) exposure has received great ecotoxicological concerns. However, huge gaps on the molecular mechanism still exist in bivalves. In this study, reproduction-related indicators were investigated in female scallops Chlamys farreri during life cycle of proliferative, growth, mature, and spawn stages, under gradient concentrations of B[a]P at 0, 0.04, 0.4, and 4 µg/L. Meanwhile, a multi-stage ovarian transcriptome analysis under 4 µg/L B[a]P exposure was also conducted to elucidate the potential molecular mechanisms. The results indicated that life-cycle exposure to 0.4 and 4 µg/L B[a]P significantly decreased GSI and sex steroid levels. Even 0.04 µg/L B[a]P could play the adverse role in DNA integrity at the mature and spawn stages. Ovarian histological sections showed that B[a]P inhibited the maturation and release of oocytes. Through the functional enrichment analysis of differentially expressed genes (DEGs) from transcriptome data, 18 genes involved in endocrine disruption effects, DNA damage and repair, and oogenesis were selected and further determined by qRT-PCR. The downregulation of genes involved in steroidogenic and estrogen signaling pathways indicated that B[a]P could cause endocrine disruption through both receptor-dependent and receptor-independent pathways. The variations of gene expressions involved in DNA single-strand break and repair implied the presence of toxic mechanisms similar with vertebrates. Additionally, the changes of gene expressions of cell cycle, apoptosis, and cell adhesion suggested that exposure to B[a]P possibly caused the reproductive toxicity effects by affecting oogenesis. Taken together, this study was a pioneer in combining genome-wide transcriptomic analysis with its corresponding reproductive indicators (GSI, sex steroid levels, DNA single-strand break, and histological sections) to explore the bivalves' toxic mechanisms under B[a]P exposure. Meanwhile, some genes involved in estrogen signaling pathway and DNA damage were firstly analyzed in bivalves, and the expression data might be useful in establishing new hypotheses and discovering new biomarkers for marine biomonitoring.
Assuntos
Benzo(a)pireno , Pectinidae , Animais , Benzo(a)pireno/metabolismo , Benzo(a)pireno/toxicidade , Estrogênios/metabolismo , Feminino , Hormônios Esteroides Gonadais/metabolismo , Pectinidae/genética , Reprodução , EsteroidesRESUMO
OBJECTIVE: To investigate the cardiovascular risk profile in patients with glycogen storage disease (GSD) type I. METHOD: The clinical information of 62 patients with GSD type I who admitted to Peking Union Medical Hospital were reviewed and the cardiovascular risk profile was analyzed. RESULTS: The age of the patient cohort was (8.4 ± 6.9) years and the ratio of male vs. female was 36:26. The median disease duration was (6.7 ± 6.2) years and treatment duration was (38.3 ± 35.2) months. The rate of abnormal change in electrocardiogram and echocardiography was 17.7% and 24.2%, respectively. The serum concentration of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and uric acid in patient before and after treatment were (6.18 ± 2.47) mmol/L vs. (5.61 ± 1.84) mmol/L (P = 0.020), (11.17 ± 9.85) mmol/L vs. (6.81 ± 5.97) mmol/L (P = 0.010), (2.55 ± 1.27) mmol/L vs. (2.78 ± 1.07) mmol/L (P = 0.617), (0.98 ± 0.37) mmol/L vs. (0.96 ± 0.23) mmol/L (P = 0.005), (526.53 ± 127.09) µmol/L vs. (490.78 ± 129.79) µmol/L (P = 0.977), respectively. The high-sensitivity C-reactive protein levels tended to be higher after therapy compared before treatment (2.33 ± 3.30) mg/L vs. (3.35 ± 3.39) mg/L, P = 0.431. CONCLUSION: Patients with GSD I are associated with an increased risk for cardiovascular disease.
Assuntos
Doenças Cardiovasculares/etiologia , Doença de Depósito de Glicogênio Tipo I/complicações , Adolescente , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Doença de Depósito de Glicogênio Tipo I/sangue , Doença de Depósito de Glicogênio Tipo I/diagnóstico por imagem , Humanos , Lactente , Lipoproteínas LDL/sangue , Masculino , Fatores de Risco , Triglicerídeos/sangue , UltrassonografiaRESUMO
Benzo[a]pyrene (B[a]P), a representative polycyclic aromatic hydrocarbon (PAH) compound in marine ecosystem, has great potential for chronic toxicity to marine animals. It is becoming increasingly apparent that reproductive system is the major target of B[a]P, but the adverse effects of B[a]P on subcellular fractions in bivalve gonads have not been elucidated. Scallops Chlamys farreri are used as the experimental species since they are sensitive to environmental pollutants. This study was conducted to investigate how B[a]P affected the gonadal subcellular fractions, including plasma membrane, nucleus, mitochondria and microsome in scallops, and whether subcellular damages were related to reproductive toxicity. The results showed that mature gametes' counts were significantly decreased in B[a]P-treated scallops. Three biological macromolecules (viz., DNA, lipids and proteins) in gonadal subcellular fractions obtained by differential centrifugation suffered damages, including DNA damage, lipid peroxidation and protein carbonylation in B[a]P treatment groups. Interestingly, mitochondria and microsome were more vulnerable to lipid peroxidation and protein carbonylation than plasma membrane and nucleus, meanwhile males were more susceptible to DNA damage than females under B[a]P exposure. In addition, histological analysis showed that B[a]P delayed gonadal development in C. farreri. To summarize, our results indicated that B[a]P caused damages to biological macromolecules in gonadal subcellular fractions and then induced damages to gonadal tissues of C. farreri, which further inhibited gonadal development and ultimately leaded to reduction in fertility. This study firstly reports the impacts of PAHs on subcellular fractions in bivalves and their relationship with reproductive toxicity. Moreover, exposure of reproductive scallops to B[a]P leads to defects in reproduction, raising concerns on the possible long-term consequences of PAHs for natural populations of bivalves.