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1.
J Neurochem ; 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37924265

RESUMO

Sex differences in pain sensitivity have contributed to the fact that medications for curing chronic pain are unsatisfactory. However, the underlying mechanism remains to be elucidated. Brain-derived estrogen participates in modulation of sex differences in pain and related emotion. G protein-coupled receptor 30 (GPR30), identified as a novel estrogen receptor with a different distribution than traditional receptors, has been proved to play a vital role in regulating pain affected by estrogen. However, the contribution of its distribution to sexually dimorphic pain-related behaviors has not been fully explored. In the current study, immunofluorescence assays were applied to mark the neurons expressing GPR30 in male and female mice (in metestrus and proestrus phase) in pain-related brain regions. The neurons that express CaMKIIα or VGAT were also labeled to observe overlap with GPR30. We found that females had more GPR30-positive (GPR30+ ) neurons in the primary somatosensory (S1) and insular cortex (IC) than males. In the lateral habenula (LHb) and the nucleus tractus solitarius (NTS), males had more GPR30+ neurons than females. Moreover, within the LHb, the expression of GPR30 varied with estrous cycle phase; females in metestrus had fewer GPR30+ neurons than those in proestrus. In addition, females had more GPR30+ neurons, which co-expressed CaMKIIα in the medial preoptic nucleus (mPOA) than males, while males had more than females in the basolateral complex of the amygdala (BLA). These findings may partly explain the different modulatory effects of GPR30 in pain and related emotional phenotypes between sexes and provide a basis for comprehension of sexual dimorphism in pain related to estrogen and GPR30, and finally provide new targets for exploiting new treatments of sex-specific pain.

2.
Fish Shellfish Immunol ; 139: 108910, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37385463

RESUMO

Berberine (BBR) is known for its strong antioxidant, anti-inflammatory, and capacity to preserve intestinal microbiota balance in fish. This study aimed to investigate the protective effects of berberine against copper-induced toxicity in the intestine of freshwater grouper Acrossocheilus fasciatus. The experiment involved four groups: a control group, a Cu group exposed to 0.02 mg/L Cu2+, and two BBR groups fed with 100 or 400 mg/kg of berberine diets and exposed to the same Cu2+ concentration. Three replicates of healthy fish (initial weight 1.56 ± 0.10 g) were subjected to their respective treatments for 30 days. Results showed that none of the treatments significantly affected the survival rate, final weight, weight gain, and feed intake (P > 0.05). However, supplementation with 100 and 400 mg/kg of BBR significantly lowered the antioxidant activities, and glutathione peroxidase (gpx) and superoxide dismutase (sod) expression levels, as well as reduced malondialdehyde (MDA) content caused by Cu2+ exposure (P < 0.05). Berberine inclusion significantly downregulated proinflammatory factors NLR family pyrin domain containing 3 (nlrp3), interleukin 1 beta (il1ß), interleukin 6 cytokine family signal transducer (il6st) but upregulated transforming growth factor beta 1 (tgfß1) and heat shock 70 kDa protein (hsp70) expression. Moreover, berberine at both levels maintained the intestinal structural integrity and significantly improved gap junction gamma-1 (gjc1) mRNA level compared to the Cu group (P < 0.05). Based on 16S rDNA sequencing, the richness and diversity of intestinal microbiota in different groups were not significantly influenced. Berberine reduced the Firmicutes/Bacteroidota ratio and stifled the growth of some specific pathogenic bacteria such as Pseudomonas, Citrobacter, and Acinetobacter, while boosting the richness of potential probiotic bacteria, including Roseomonas and Reyranella compared with the Cu group. In conclusion, berberine showed significant protective effects against Cu2+-induced intestinal oxidative stress, inflammation response, and microbiota disturbance in freshwater grouper.


Assuntos
Bass , Berberina , Cyprinidae , Microbiota , Animais , Antioxidantes/metabolismo , Cobre/toxicidade , Berberina/farmacologia , Bass/metabolismo , Estresse Oxidativo , Intestinos , Dieta , Cyprinidae/metabolismo , Inflamação/induzido quimicamente , Inflamação/veterinária
3.
BMC Cancer ; 21(1): 321, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765976

RESUMO

BACKGROUND: We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. METHODS: RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. RESULTS: RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. CONCLUSION: The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Recombinantes de Fusão/farmacologia , Antineoplásicos Imunológicos/isolamento & purificação , Antineoplásicos Imunológicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Humanos , Imunoconjugados/genética , Imunoconjugados/isolamento & purificação , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/uso terapêutico , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/isolamento & purificação , Anticorpos de Cadeia Única/farmacologia , Anticorpos de Cadeia Única/uso terapêutico
4.
FASEB J ; 34(8): 10623-10639, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32596959

RESUMO

Although renal cell carcinoma (RCC) is a common malignant urological cancer, its pathogenesis remains unclear. Previous studies have indicated that miR-140-5p acts as a tumor suppressor in various tumors, including bladder cancer, hepatocellular carcinoma, and gastric cancer, but its biological function in RCC remains unknown. In the present study, we found that miR-140-5p was upregulated in RCC tissues, whereas Krüppel-like factor 9 (KLF9) was downregulated and correlated inversely with miR-140-5p in RCC tissues. miR-140-5p promoted the proliferation, migration, and invasion of RCC cells in vitro, and knockdown of miR-140-5p significantly suppressed tumor growth and lung metastasis in nude mouse model of RCC. We also found that miR-140-5p significantly suppressed the expression of KLF9 by binding to the 3'-UTR of KLF9 mRNA and that KLF9, as a transcription factor, upregulates KCNQ1 (also called Kv 7.1 and Kv LQT1) expression by binding to the site (-841/-827) in the KCNQ1 promoter region in RCC cells. Moreover, forced expression of KCNQ1 decreased the growth and metastasis of RCC cells. These results suggest that the miR-140-5p/KLF9/KCNQ1 axis functions as a key signaling pathway in RCC progression and metastasis and represents a potential target of RCC therapies.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Canal de Potássio KCNQ1/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Regiões 3' não Traduzidas/genética , Animais , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Células HEK293 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Regulação para Cima/genética
5.
Environ Sci Technol ; 55(11): 7731-7740, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34003641

RESUMO

In this study, the carbon and chlorine isotope fractionation during ultraviolet-photolysis of polychlorinated biphenyls (PCBs, including PCB18, PCB77, PCB110, and PCB138) in n-hexane (Hex), methanol/water (MeOH/H2O), and silica gel was first investigated to explore their mechanistic processes. We observed a significant variation in ΛCl-C (εCl/εC) for the same PCBs in different photochemical systems, implying that PCB degradation processes in various photoreaction systems could differ. Although all substrates showed normal apparent carbon/chlorine kinetic isotope effects (C-/Cl-AKIE >1), the putative inverse C-AKIE of nondechlorinated pathways was suggested by 13C depletion of the average carbon isotope composition of PCB138 and corresponding dechlorinated products in MeOH/H2O, which might originate from the magnetic isotope effect. Significant negative correlations were found between C-AKIE and relative disappearance quantum yields ("Φ") of ortho-dechlorinated substrates (PCB18, PCB110, and PCB138) in Hex and MeOH/H2O. However, the C-AKIE and "Φ" of PCB77 (meta/para-dechlorinated congener) obviously deviated from the above correlations. Furthermore, significantly different product-related carbon isotope enrichment factors of PCB77 in Hex were found. These results demonstrated the existence of dechlorination position-specific and masking effects in carbon isotope fractionations.


Assuntos
Bifenilos Policlorados , Carbono , Isótopos de Carbono , Fracionamento Químico , Cloro
6.
Environ Sci Technol ; 55(14): 9579-9590, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-33852286

RESUMO

Surface sediments of polluted urban rivers can be a reservoir of hydrophobic persistent organic pollutants (POPs). In this study, we comprehensively assessed the contamination of two groups of POPs, that is, polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), in 173 black-odorous urban rivers in China. Spatial distribution of PCBs and PBDEs showed similar patterns but very different contamination levels in surface sediments, that is, average concentrations of 10.73 and 401.16 ng/g dw for the ∑PCBs and ∑PBDEs, respectively. Tetra-/di-CBs and deca-BDE are major PCBs and PBDEs and accounted for 59.11 and 95.11 wt % of the ∑PCBs and ∑PBDEs, respectively. Compared with the persistence of PBDEs, the EF changes of chiral PCBs together with previous cultivation evidence indicated indigenous bioconversion of PCBs in black-odorous urban rivers, particularly the involvement of uncharacterized Dehalococcoidia in PCB dechlorination. Major PCB sources (and their relative contributions) included pigment/painting (25.36%), e-waste (22.92%), metallurgical industry (13.25%), and e-waste/biological degradation process (10.95%). A risk assessment indicated that exposure of resident organisms in urban river sediments to deca-/penta-BDEs could pose a high ecological risk. This study provides the first insight into the contamination, conversion and ecological risk of PCBs and PBDEs in nationwide polluted urban rivers in China.


Assuntos
Bifenilos Policlorados , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Éteres Difenil Halogenados/análise , Bifenilos Policlorados/análise , Rios , Poluentes Químicos da Água/análise
7.
J Cell Mol Med ; 24(12): 6609-6621, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32342645

RESUMO

Growing evidence indicates that circular RNAs (circRNAs) are promising biomarkers, as they play significant roles in the development of various cancers. The circular RNA MYLK (circMYLK) has been reported to be involved in the development of malignant tumours, including liver, prostate and bladder cancers. Nevertheless, the biological function of circMYLK in renal cell carcinoma (RCC) remains unclear. In this study, we observed that circMYLK is notably up-regulated in RCC. Increased circMYLK expression led to a larger tumour size, distant metastasis and poor prognosis of RCC patients. Moreover, circMYLK silencing repressed RCC growth and metastasis in vitro and in vivo. Mechanistically, circMYLK can capture miR-513a-5p to facilitate VEGFC expression and further promote the tumorigenesis of RCC cells. In summary, our findings demonstrate that circMYLK has an oncogenic role in RCC growth and metastasis by modulating miR-513a-5p/VEGFC signalling. Thus, circMYLK has potential as a diagnostic biomarker and therapeutic target in the treatment of RCC.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , MicroRNAs/genética , RNA Circular/metabolismo , Transdução de Sinais , Fator C de Crescimento do Endotélio Vascular/metabolismo , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , RNA Circular/genética
8.
J Cell Mol Med ; 24(16): 9231-9243, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32596993

RESUMO

Growing evidence suggests that long non-coding RNAs (lncRNAs) are associated with carcinogenesis. LncRNA small nucleolar RNA host gene 3 (SNHG3) is up-regulated in various cancers and positively associated with poor prognosis of these cancers. However, the precise role of lncRNA SNHG3 in bladder cancer (Bca) remains unclear. In our research, we first reported that lncRNA SNHG3 was up-regulated in bladder cancer tissues and positively related to poor clinical prognosis. Moreover, knockdown of lncRNA SNHG3 significantly suppressed the proliferation, migration, invasion and EMT process of Bca cells in vitro and vivo. Mechanistically, we revealed that suppression of SNHG3 evidently enhanced miR-515-5p expression and decreased GINS2 expression at posttranscriptional levels. Moreover, SNHG3 positively regulated GINS2 expression by sponging miR-515-5p under a competing endogenous RNA (ceRNA) mechanism. To sum up, our study suggested lncRNA SNHG3 acted as a microRNA sponge and an oncogenic role in the progression of bladder cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Proteínas Cromossômicas não Histona/genética , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Humanos , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Mol Cancer ; 19(1): 103, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503552

RESUMO

BACKGROUND: Circular RNAs (circRNAs), a novel type of noncoding RNA (ncRNA), are covalently linked circular configurations that form via a loop structure. Accumulating evidence indicates that circRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise roles of circRNAs in renal cell carcinoma (RCC) remain unknown. METHODS: Through circRNA high-throughput sequencing of RCC cell lines, we identified the circRNA TLK1 (circTLK1) as a novel candidate circRNA derived from the TLK1 gene. qRT-PCR detected the mRNA, circRNA and miRNA expression levels in RCC tissues and cells. Loss-of function experiments were executed to detect the biological roles of circTLK1 in the RCC cell phenotypes in vitro and in vivo. RNA-FISH, RNA pull-down, dual-luciferase reporter, western blot and immunohistochemistry assays were used to investigate the molecular mechanisms underlying the functions of circTLK1. RESULTS: circTLK1 is overexpressed in RCC, and expression is positively correlated with distant metastasis and unfavorable prognosis. Silencing circTLK1 significantly inhibited RCC cell proliferation, migration and invasion in vitro and in vivo. circTLK1 was mainly distributed in the cytoplasm and positively regulated CBX4 expression by sponging miR-136-5p. Forced CBX4 expression reversed the circTLK1 suppression-induced phenotypic inhibition of RCC cells. Moreover, CBX4 expression was positively correlated with VEGFA expression in RCC tissues. CBX4 knockdown significantly inhibited VEGFA expression in RCC cells. CONCLUSION: Collectively, our findings demonstrate that circTLK1 plays a critical role in RCC progression by sponging miR-136-5p to increase CBX4 expression. circTLK1 may act as a diagnostic biomarker and therapeutic target for RCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Ligases/metabolismo , MicroRNAs/genética , Proteínas do Grupo Polycomb/metabolismo , Proteínas Serina-Treonina Quinases/genética , RNA Circular/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Ligases/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Proteínas do Grupo Polycomb/genética , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Mol Cell ; 45(5): 669-79, 2012 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-22306294

RESUMO

During embryonic cell cycles, B-cyclin-CDKs function as the core component of an autonomous oscillator. Current models for the cell-cycle oscillator in nonembryonic cells are slightly more complex, incorporating multiple G1, S phase, and mitotic cyclin-CDK complexes. However, periodic events persist in yeast cells lacking all S phase and mitotic B-cyclin genes, challenging the assertion that cyclin-CDK complexes are essential for oscillations. These and other results led to the proposal that a network of sequentially activated transcription factors functions as an underlying cell-cycle oscillator. Here we examine the individual contributions of a transcription factor network and cyclin-CDKs to the maintenance of cell-cycle oscillations. Our findings suggest that while cyclin-CDKs are not required for oscillations, they do contribute to oscillation robustness. A model emerges in which cyclin expression (thereby, CDK activity) is entrained to an autonomous transcriptional oscillator. CDKs then modulate oscillator function and serve as effectors of the oscillator.


Assuntos
Ciclo Celular/genética , Quinases Ciclina-Dependentes/fisiologia , Regulação Fúngica da Expressão Gênica , Fatores de Transcrição/fisiologia , Leveduras/citologia , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Proteína Quinase CDC2/fisiologia , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Leveduras/enzimologia , Leveduras/genética
11.
Environ Sci Technol ; 53(4): 1928-1936, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30644732

RESUMO

In the present study, positive matrix factorization (PMF) and compound-specific isotope analysis were used to investigate the in situ biodegradation of polybrominated diphenyl ethers (PBDEs) in sediment cores collected from a pond at an e-waste recycling site in South China. The potential microorganisms relevant to the degradation of PBDEs were also assessed to aid in the understanding of in situ biodegradation. The PMF results suggested that reductive debromination took place in the sediments. The debromination signal (ratio of the concentration of factor 5 (PMF result) to the total PBDE content) was positively correlated with the relative abundance of Dehalococcoidetes at different core depths. The clear 13C enrichment of five PBDE congeners (BDE 28, 47, 49, 99, and 153) with increasing core depth indicated that a measurable change in isotope fractionation might have occurred during PBDE biodegradation. The in situ biodegradation was further validated by the widespread detection of mono-BDE congeners (BDE 2, BDE 3) and diphenyl ether in the sediments. This study provides new evidence to enhance our understanding of the in situ biodegradation of PBDEs and suggests that the extensive removal of bromine from PBDEs was mediated by indigenous microorganisms at the e-waste site.


Assuntos
Resíduo Eletrônico , Poluentes Químicos da Água , Carbono , Isótopos de Carbono , China , Sedimentos Geológicos , Éteres Difenil Halogenados
13.
Environ Sci Technol ; 52(18): 10359-10368, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30160487

RESUMO

Two artificial food chains, food tiger barb-oscar fish and food tiger barb-redtail catfish, were established in the laboratory. The species-specific biotransformation of ortho, para'-dichlorodiphenyltrichloroethane, 12 polychlorinated biphenyl, and five polybrominated diphenyl ether congeners were characterized by measuring the compound- and enantiomer-specific stable carbon isotope composition (δ13C), enantiomeric fraction of the chiral chemicals, and metabolites in the fish. Compound- and enantiomer-specific biotransformations were revealed by the alteration of δ13C and EF in both predator fish species. Significant correlations between the carbon stable isotope signatures and the depuration rates and biomagnification factors (BMF) were observed. Chemicals that exhibited changes in δ13C during the experiment have higher kd and lower BMF values than those with unchanged δ13C. Specifically, the difference between the predicted BMF based on the log Kow and the measured BMF, ΔBMF, was significantly positively and linearly correlated to the change in the δ13C (expressed by Δδ13C/δ13Cinitial, the percentage of Δδ13C: δ13Cending-δ13Cinitial to the initial δ13Cinitial) in both food chains. These results indicated that the impact of metabolism on the bioaccumulation potential of organic contaminants can be predicted by the stable carbon isotope fractionation of chemicals in the fish.


Assuntos
Cadeia Alimentar , Bifenilos Policlorados , Animais , Carbono , Isótopos de Carbono , Éteres Difenil Halogenados
15.
J Cancer ; 15(5): 1191-1202, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356717

RESUMO

Background: P7C3 is a novel compound that has been widely applied in neurodegenerative diseases and nerve injury repair. Here, we show that higher concentrations of P7C3 than are required for in vivo neuroprotection have the novel function of suppressing renal cell carcinoma (RCC) proliferation and metastasis. Methods: Colony formation, CCK-8 and EdU assay were applied to evaluate RCC cell proliferation. Wound healing and transwell assay were used to measure RCC cell migration and invasion. Flow cytometry assay was employed to detect RCC cell apoptosis and cell cycle. qRT-PCR assay was carried out to measure ribonucleotide reductase subunit M2 (RRM2) mRNA expression level, while western blot assay was utilized to detect the expression level of target proteins. RCC cell growth in vivo was determined by xenografts in mice. Results: We observed that high concentrations of P7C3 could restrain the proliferation and metastasis of RCC cells and promote cell apoptosis. Mechanistically, this new effect of higher dose of P7C3 was associated with reduced expression of RRM2, and the beneficial efficacy of P7C3 in RCC was blocked when suppression of RRM2 was prevented. When RRM2 suppression was permitted, the cGAS-STING pathway was activated by virtue of RRM2/Bcl-2/Bax signaling. Lastly, intraperitoneal injection of this high level of P7C3 in mice potently inhibited tumor growth. Conclusion: In conclusion, we show here that P7C3 that exerts an anti-cancer effect in RCC. Our study indicated that P7C3 might act as a novel drug for RCC in the future. The regulatory signal pathway RRM2/Bcl-2/BAX/cGAS-STING might present novel insight to the potential mechanism of RCC development.

16.
Toxics ; 12(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38251039

RESUMO

Novel brominated flame retardants (NBFRs) and dechlorane plus (DP) have been widely used as alternatives to traditional BFRs. However, little is known about the temporal trends of NBFR and DP pollution in e-waste recycling sites. In the current study, three composite sediment cores were collected from an e-waste-polluted pond located in a typical e-waste recycling site in South China to investigate the historical occurrence and composition of NBFRs and DP. The NBFRs and DP were detected in all layers of the sediment cores with concentration ranges of 5.71~180,895 and 4.95~109,847 ng/g dw, respectively. Except for 2,3,5,6-tetrabromo-p-xylene (pTBX) and 2,3,4,5,6-pentabromoethylbenzene (PBEB), all the NBFR compounds and DP showed a clear increasing trend from the bottom to top layers. These results implied the long-term and severe contamination of NBFRs and DP. Decabromodiphenyl ethane (DBDPE) was the most abundant NBFR with the contribution proportions of 58 ± 15%, 73 ± 15%, and 71 ± 18% in three sediment cores, followed by 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE) and pentabromobenzene (HBB). The ratios of BTBPE/Octa-BDEs and DBDPE/Deca-BDEs varied from 0.12 to 60 and from 0.03 to 0.49, respectively, which had no clear increase trends with a decrease in sediment depth. As for DP, the fanti values (the concentration ratios of anti-DP to the sum of anti-DP and syn-DP) in sediment cores ranged from 0.41 to 0.83, almost falling in the range of those in DP technical products, suggesting that DP degradation did not occur in sediment cores. The environmental burdens of DBDPE, BTBPE, HBB, PBT, PBEB, pTBX, and DP were estimated to be 34.0, 5.67, 10.1, 0.02, 0.02, 0.01, and 34.8 kg, respectively. This work provides the first insight into the historical contamination status of NBFRs and DP in the sediments of an e-waste recycling site.

17.
Sci Total Environ ; 915: 170108, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38232851

RESUMO

Organophosphate triesters (tri-OPEs) are a kind of widespread contaminants in the world, particularly in China, which is a major producer and user of tri-OPEs. However, tri-OPE pollution in urban river sediments in China remains unclear. In current work, we carried out the first nationwide investigation to comprehensively monitor 10 conventional and five emerging tri-OPEs in sediments of 173 black-odorous urban rivers throughout China. Concentrations of 10 conventional and five emerging tri-OPEs were 3.8-1240 ng/g dw (mean: 253 ng/g dw) and 0.21-1107 ng/g dw (68 ng/g dw), respectively, and significantly differed among the cities sampled but generally decreased from Northeast and East China to Central and West China. These spatial patterns suggest that tri-OPE pollution was mainly from local sources and was controlled by the industrial and economic development levels in these four areas, as indicated by the significant correlations between tri-OPE concentrations and gross domestic production, gross industrial output, and daily wastewater treatment capacity. Although the tri-OPE composition varied spatially at different sites, which indicated different tri-OPE input patterns, it was commonly dominated by tris(2-chloroethyl) phosphate, tris(2-ethylhexyl) phosphate, and tris(1-chloro-2-propyl) phosphate (conventional tri-OPEs) and bisphenol A-bis(diphenyl phosphate) and isodecyl diphenyl phosphate (emerging tri-OPEs). A risk assessment indicated that tri-OPEs in most sampling sediments had a low to moderate risk to aquatic organisms.

19.
Sci Total Environ ; 907: 168057, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37898190

RESUMO

Hexabromocyclododecanes (HBCDs) have become a global pollution problem, particularly in China-a major producer and user of HBCDs. However, little is known about the HBCD pollution status in urban rivers nationwide in China. In this study, we comprehensively investigated the pollution characteristics of HBCDs in 173 sediment samples from black-odorous urban rivers across China. Total HBCD concentrations ranged from not-detected to 848 ng/g dw, showing significant differences among the various sampling cities, but generally increasing from west to east China. This distribution pattern of HBCDs was strongly associated with the local industrial output, gross domestic product, and daily wastewater treatment capacity. α-HBCD was the predominant diastereoisomer in most sediments, with an average proportion of 63.8 ± 18.8 %, followed by γ-HBCD (23.8 ± 19.5 %) and ß-HBCD (12.4 ± 6.49 %), showing a significant increase of the α-HBCD proportions relative to those in HBCD commercial mixtures and an opposite trend for that of γ-HBCD. These results suggested that HBCDs might undergo isomerization from γ- to α-HBCD and biotic/abiotic degradation with preference for γ-HBCD. Of these conversions, the microbial degradation of HBCDs was further verified by the preferential transformation of (-)-α-, (+)-ß-, and (-)-γ-HBCDs and the detection of HBCD-degrading bacteria, including Dehalococcoides, Bacillus, Sphingobium, and Pseudomonas. A risk assessment indicated that HBCDs pose low to moderate risks to aquatic organisms in most black-odorous urban river sediments.


Assuntos
Retardadores de Chama , Hidrocarbonetos Bromados , Rios , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Hidrocarbonetos Bromados/análise , China , Medição de Risco , Retardadores de Chama/análise
20.
Environ Sci Pollut Res Int ; 31(11): 17472-17480, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342836

RESUMO

China, one of the two dechlorane plus (DP) producers, might have become a major area of DP pollution. The environmental contamination status of DP in sediments across the whole of China has not yet been studied. In the current study, the pollution levels, spatial distribution, and compositions of DP were investigated comprehensively in surface sediments from 173 black-odorous urban rivers across China for the first time. Total DP concentrations varied from not-detected to 39.71 ng/g dw, with an average concentration of 3.20 ± 4.74 ng/g dw, which was polluted by local emission sources and presented significant differences among different sampling cities. Among the seven administrative regions of China, DP concentrations were the highest in South China and showed a decreasing trend from southeastern coastal areas to northwest inland regions. Spearman's correlation analysis suggested that the gross industrial output, gross domestic product, and daily wastewater treatment capacity were not the principal factors controlling the spatial distribution of DP. The fanti values (the concentration ratios of anti-DP to the sum of anti-DP and syn-DP) varied from 0.19 to 0.88, with those in most sediments falling in the range of DP technical product (0.60 ~ 0.80), suggesting no apparent stereoselective enrichment occurred. Moreover, the anti-Cl11-DP was detected in sediments (n.d. ~ 0.40 ng/g dw), which showed significantly and insignificantly positive correlation with the anti-DP levels and fanti, respectively, implying it might mainly originate from the byproduct of DP technical product rather than the dechlorination of anti-DP.


Assuntos
Retardadores de Chama , Hidrocarbonetos Clorados , Compostos Policíclicos , Poluentes Químicos da Água , Sedimentos Geológicos , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Retardadores de Chama/análise , Hidrocarbonetos Clorados/análise , Compostos Policíclicos/análise , Rios , China
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