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1.
Sci Total Environ ; 775: 145846, 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33631569

RESUMO

In recent years, natural particles in drinking water have attracted attention due to their carry of toxic organic matter. However, the adsorption behavior of multiple antibiotics at very low concentrations on different sized particles has not been revealed. Here, the content of 17 antibiotics in water samples collected from four process stages of the water supply plant was detected. Results showed the concentration of antibiotics in water plant was in the range of 0-69.24 ng L-1. Characterization of natural particles obtained directly from raw water of waterworks showed that the surface of large particles (>1 µm) was rougher and the composition was more complex than that of small particles (0.05-1 µm). Besides, the adsorption experiments of four antibiotics (nalidixic acid (NAL), trimethoprim (TMP), roxithromycin (ROX), and penicillin G potassium salt (PG)) on small (0.05-1 µm) and large (>1 µm) natural particles were studied. The results indicated that in the binary antibiotic system, the competition and synergy between antibiotics made a greater proportion of antibiotics soluble in water comparing with single systems, and the particle-water partition coefficient (kp-w) of the total antibiotics ranged from 1.13-1.78 was reduced to 0.57-0.84. The competitive adsorption of antibiotics appeared in the binary system showed that ROX and PG had a higher adsorption capacity than NAL and TMP. Furthermore, in the binary antibiotic systems, small particles played an important role in adsorption, suggesting the urgency of their removing. This work could help predict the possible risks of drinking water and provide some insights into future drinking water treatment.

2.
Toxicol Lett ; 342: 6-19, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33581290

RESUMO

2,2',4,4'-Tetrabromodiphenyl ether (BDE47), a flame retardant, is extensively distributed in the food chain. However, whether BDE47 affects Leydig cell development during prepuberty remains unclear. BDE47 was daily gavaged to 21-day-old Sprague-Dawley male rats with 0 (corn oil), 0.1, 0.2, and 0.4 mg/kg for 14 days. BDE47 did not affect the body weight or testis weight of rats. It significantly increased serum testosterone level at 0.4 mg/kg, but decreased luteinizing hormone (LH) level without affecting estradiol level. BDE47 induced Leydig cell hyperplasia (the number of CYP11A1-positive Leydig cells increased), and up-regulated the expression of Scarb1, Star, Hsd11b1, Pcna, and Ccnd1 in the testis. BDE47 significantly reduced p53 and p21 levels but increased CCND1 level. It also markedly increased the phosphorylation of AKT1, AKT2, ERK1/2, and CREB. BDE47 significantly up-regulated the expression of Scarb1, Star, and Hsd11b1 and stimulated androgen production by immature Leydig cells from rats under basal, LH, and 8Br-cAMP stimulated conditions at 100 nM in vitro. In conclusion, BDE47 increased Leydig cell number and up-regulated the expression of Scarb1 and Star, thereby leading to increased testosterone synthesis.

3.
Ann Hematol ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33389024

RESUMO

Tumour-infiltrating lymphocytes (TILs) account for a large proportion of tumour microenvironment (TME) in angioimmunoblastic T cell lymphoma (AITL), and at present the significance of TIL in TME of AITL remains unclear. Overall, 50 de novo AITL patients undergoing lymph node flow cytometry from 2014 to 2019 were retrospectively analysed to assess the relationship between TILs and AITL prognosis. We found that high TIL-Bs (≥ 42.4%, p = 0.004) and high CD4:CD8 (≥ 0.85, p = 0.024) were independent favourable prognostic factors for de novo AITL in univariate or multivariate analyses. New TIL-related risk stratification was established based on TIL-Bs and CD4:CD8 factors. Patients in the low-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 ≥ 0.85) had significantly better overall survival than the high-risk (TIL-Bs < 42.4% and CD4:CD8 < 0.85) (p < 0.001) or intermediate-risk group (TIL-Bs ≥ 42.4% and CD4:CD8 < 0.85 or TIL-Bs < 42.4% and CD4:CD8 ≥ 0.85) (p = 0.011). To our knowledge, our cohort is the largest one focusing on the TILs in de novo cases of AITL by analysing lymph node samples using flow cytometry, which is the first time to comprehensively consider humoral immunity and cellular immunity influence on AITL. Our new risk stratification was valuable and useful in evaluating prognosis of AITL and guiding immunotherapy strategies.

4.
Anal Chim Acta ; 1140: 78-88, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33218492

RESUMO

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with unclear pathogenesis, for which diagnosis has been a great challenge. Recent researches have revealed that miR-3675-3p is a promising biomarker for IPF diagnosis. Herein, the present work describes a novel electrochemical microRNA biosensor for rapid and sensitive detection of miR-3675-3p based on multiple signal amplification strategies. First of all, fullerene (C60) is doped with poly(amidoamine) (PAMAM)-functionalized metal-organic framework (MOF) to form a new nanohybrid of C60@PAMAM-MOF, which exhibits more remarkable redox activity compared with the other two synthesized C60-based nanohybrids when triggered by tetraoctylammonium bromide (TOAB). C60@PAMAM-MOF also possesses a large specific surface area and abundant amino groups to anchor Au nanoparticles (AuNPs) for the immobilization of signal probe (SP) to form tracer label and enhance the electrochemical response signal. In addition, core@shell Au-Pt nanoparticles (Au@PtNPs) are absorbed on chitosan-acetylene black (CS-AB) to act as sensing platform, which can promote electron transfer and increase the loading of capture probe (CP). Under optimum conditions, the proposed biosensor displays a wide linear range for miR-3675-3p from 10 fM to 10 nM, with a limit of detection (LOD) as low as 2.99 fM. More significantly, this biosensor shows a lower LOD and wider linear range than that of qRT-PCR, and its trial application in human serum shows favorable results, which exhibits a promising prospect for IPF diagnosis.

5.
Food Chem Toxicol ; 143: 111479, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32504733

RESUMO

Triphenyltin has been classified as an endocrine disruptor. However, whether triphenyltin interferes with the adrenal glands during puberty remains unknown. Here, we reported the effects of triphenyltin on the adrenal glands in rats. Male Sprague Dawley rats (age of 35 days) were orally administered with 0, 0.5, 1, or 2 mg/kg/day triphenyltin for 18 days. Triphenyltin significantly lowered corticosterone levels at 1 and 2 mg/kg and adrenocorticotropic hormone at 2 mg/kg. The RNA-Seq analysis detected multiple differentially expressed genes. Four down-regulated genes were transcription factor genes (Nr4a1, Nr4a2, Nr4a3, and Ppard), which might be associated with the suppression of the adrenal cortex function. RNA-seq and qPCR showed that triphenyltin dose-dependently down-regulated the expression of the genes for cholesterol transport and biosynthesis, including Scarb1, Ldlr, Hmgcs1, Hmgcr, and Hsd17b7. Further Western blotting revealed that it lowered NR4A1, PPRAD, LDLR, and HMGCS1 protein levels. We treated H295R adrenal cells with 1-100 nM triphenyltin for 72 h. Triphenyltin induced significant higher ROS production at 100 nM and did not induce apoptosis at 10 and 100 nM. In conclusion, triphenyltin inhibits production of corticosterone via blocking the expression of cholesterol uptake transporters and cholesterol biosynthesis.

6.
Front Genet ; 11: 527, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528534

RESUMO

Cadmium is a heavy metal, and people are exposed to it through contaminated foods and smoking. In humans and other mammals, cadmium causes damage to male testis. In this review, we summarize the effects of cadmium on the development and function of the testis. Cadmium causes severe structural damage to the seminiferous tubules, Sertoli cells, and blood-testis barrier, thus leading to the loss of sperm. Cadmium hinders Leydig cell development, inhibits Leydig cell function, and induces Leydig cell tumors. Cadmium also disrupts the vascular system of the testis. Cadmium is a reactive oxygen species inducer and possibly induces DNA damage, thus epigenetically regulating somatic cell and germ cell function, leading to male subfertility/infertility.

7.
Toxicol Lett ; 330: 23-29, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32387388

RESUMO

Diisodecyl phthalate (DIDP) is one of synthetic phthalate plasticizers. It is widely used in plastic products and is a potential endocrine disruptor. However, the effects of DIDP on fetal testicular cell development remain unclear. The objective of the present study was to determine the effects of DIDP on fetal testis development in rats after in utero exposure. Sprague Dawley dams were randomly divided into 5 groups and were daily gavaged with DIDP (0, 10, 100, 500, and 1000 mg/kg body weight) from gestational day 14-21. Serum testosterone levels, fetal Leydig cell number and distribution, testicular gene and protein expression in male pups were examined. DIDP decreased serum testosterone levels at 1000 mg/kg (1.37 ± 0.40 ng/mL, mean ± SE) when compared to the control level (3.14 ± 0.60 ng/mL). DIDP did not affect numbers of Leydig and Sertoli cells. DIDP significantly induced abnormal aggregation of fetal Leydig cells and increased the incidence of multinucleated gonocytes at 1000 mg/kg. Furthermore, DIDP down-regulated expression of Star, Cyp11a1, Hsd17b3, and Insl3 in fetal Leydig cells at 1000 mg/kg and Sox9 in Sertoli cells at 1000 mg/kg. In conclusion, the current study indicates that in utero exposure to high-dose DIDP disrupts the development of fetal testicular cells, thus affecting the male reproductive system.

8.
Chemosphere ; 253: 126764, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32464778

RESUMO

Perfluoroalkyl substances (PFASs) are a group of man-made organic substances. Some of PFASs have been classified as persistent organic pollutants and endocrine disruptors. They might interfere with the male sex endocrine system, causing the abnormal development of the male reproductive tract and failure of pubertal onset and infertility. The present review discusses the development and function of two generations of Leydig cells in rodents and the effects of PFASs on Leydig cell development after their exposure in gestational and postnatal periods. We also discuss human epidemiological data for the effects of PFASs on male sex hormone levels. The structure-activity relationship of PFASs on Leydig cell steroidogenesis and enzyme activities are also discussed.


Assuntos
Disruptores Endócrinos/toxicidade , Fluorcarbonetos/toxicidade , Células Intersticiais do Testículo/fisiologia , Poluentes Ambientais , Humanos , Masculino
9.
J Cell Mol Med ; 24(13): 7313-7330, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32441057

RESUMO

Epidermal growth factor (EGF) has many physiological roles. However, its effects on stem and progenitor Leydig cell development remain unclear. Rat stem and progenitor Leydig cells were cultured with different concentrations of EGF alone or in combination with EGF antagonist, erlotinib or cetuximab. EGF (1 and 10 ng/mL) stimulated the proliferation of stem Leydig cells on the surface of seminiferous tubules and isolated CD90+ stem Leydig cells and progenitor Leydig cells but it blocked their differentiation. EGF also exerted anti-apoptotic effects of progenitor Leydig cells. Erlotinib and cetuximab are able to reverse EGF-mediated action. Gene microarray and qPCR of EGF-treated progenitor Leydig cells revealed that the down-regulation of steroidogenesis-related proteins (Star and Hsd3b1) and antioxidative genes. It was found that EGF acted as a proliferative agent via increasing phosphorylation of AKT1. In conclusion, EGF stimulates the proliferation of rat stem and progenitor Leydig cells but blocks their differentiation.

10.
J Biochem Mol Toxicol ; 34(8): e22505, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32275808

RESUMO

Abamectin (ABA) as one of the worldwide used compounds in agriculture has raised safety concerns on nontarget organism toxicity. However, the study of male reproductive system damage caused by ABA remains unclear. Our aim is to investigate the effect of ABA-induced cytotoxicity in TM3 Leydig cells and their underlying mechanisms. ABA inhibits TM3 cell viability and proliferation via cell cycle arrested in the G0/G1 phase. In addition, ABA-induced mitochondrial depolarization leads to an imbalance in Bcl-2 family expression, causing caspase-dependent apoptosis in TM3 cells. The increased ratio of cells expression LC3 protein and LC3-II to LC3-I indicated the activation of autophagy potentially. Further experiments revealed ABA treatment reduced phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) phosphorylation, and mammalian target of rapamycin (mTOR) phosphorylation. Pretreatment with a PI3K/AKT inhibitor, LY294002, mimicked the ABA-mediated effects on cytotoxicity. Pretreatment with a PI3K/AKT agonist, insulin-like growth factor-1, reversed the effects of ABA. ABA caused the accumulation of intracellular reactive oxygen species (ROS) by increased intensity of the ROS indicator. However, N-acetylcysteine as ROS scavengers inhibited ABA-induced apoptosis and autophagy and reversed these ABA-mediated effects on PI3K/AKT/mTOR pathway. On the basis of the above results, it is suggested that ABA exposure induces apoptosis and autophagy in TM3 cells by ROS accumulation to mediate PI3K/AKT/mTOR signaling pathway suppression.

11.
Oxid Med Cell Longev ; 2020: 4253457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190173

RESUMO

Myocardial ischemic postconditioning- (IPo-) mediated cardioprotection against myocardial ischemia-reperfusion (IR) injury needs the activation of signal transducer and activator of transcription 3 (STAT3), which involves adiponectin (APN). APN confers its biological effects through AMP-activated protein kinase- (AMPK-) dependent and AMPK-independent pathways. However, the role of AMPK in APN-mediated STAT3 activation in IPo cardioprotection is unknown. We hypothesized that APN-mediated STAT3 activation in IPo is AMPK-independent and that APN through AMPK-dependent STAT3 activation facilitates IPo cardioprotection. Here, Sprague-Dawley rats were subjected to myocardial IR without or with IPo and/or APN. APN or IPo significantly improved postischemic cardiac function and reduced myocardial injury and oxidative stress, and their combination further attenuated postischemic myocardial injuries. APN or its combination with IPo but not IPo alone significantly increased AMPK activation and both nuclear and mitochondrial STAT3 activation, while IPo significantly enhanced mitochondrial but not nuclear STAT3 activation. In primarily isolated cardiomyocytes, recombined globular APN (gAd), hypoxic postconditioning (HPo), or their combination significantly attenuated hypoxia/reoxygenation-induced cell injury and increased nuclear and/or mitochondrial STAT3 activation. STAT3 inhibition had no impact on gAd or gAd in combination with HPo-induced AMPK activation but abolished their cellular protective effects. AMPK inhibition did not affect HPo cardioprotection but abolished gAd cardioprotection and disabled gAd to facilitate/enhance HPo cardioprotection and STAT3 activation. These results suggest that APN confers cardioprotection through AMPK-dependent and AMPK-independent STAT3 activation, while IPo confers cardioprotection through AMPK-independent mitochondrial STAT3 activation. Joint use of APN and IPo synergistically attenuated myocardial IR injury by activating STAT3 via distinct signaling pathways.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/farmacologia , Cardiotônicos/metabolismo , Núcleo Celular/metabolismo , Mitocôndrias/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Animais , Hipóxia Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Pós-Condicionamento Isquêmico , Masculino , Mitocôndrias/efeitos dos fármacos , Miocárdio/enzimologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
12.
Chemosphere ; 245: 125597, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31864041

RESUMO

Acephate is an organophosphate pesticide. It is widely used. However, whether it inhibits androgen synthesis and metabolism remains unclear. In the current study, we investigated the effect of acephate on the inhibition of androgen synthetic and metabolic pathways in rat immature Leydig cells after 3-h culture. Acephate inhibited basal androgen output in a dose-dependent manner with the inhibition starting at 0.5 µM. It significantly inhibited luteinizing hormone and 8-Br-cAMP stimulated androgen output at 50 µM. It significantly inhibited progesterone-mediated androgen output at 50 µM. Further study demonstrated that acephate down-regulated the expression of Hsd3b1 and its protein at ≥ 0.5 µM, Lhcgr at 5 µM and Star at 50 µM. Acephate directly blocked rat testicular HSD3B1 activity at 50 µM. Acephate did not affect other androgen synthetic and metabolic enzyme activities as well as ROS production, proliferation, and apoptosis of immature Leydig cells. In conclusion, acephate targets LHCGR, STAR, and HSD3B1, thus blocking androgen synthesis in rat immature Leydig cells and HSD3B1 is being the most sensitive target of acephate.


Assuntos
Androgênios/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Compostos Organotiofosforados/farmacologia , Fosforamidas/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/análogos & derivados , 8-Bromo Monofosfato de Adenosina Cíclica/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Células Intersticiais do Testículo/metabolismo , Hormônio Luteinizante/antagonistas & inibidores , Hormônio Luteinizante/metabolismo , Masculino , Complexos Multienzimáticos/antagonistas & inibidores , Progesterona/farmacologia , Progesterona Redutase/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Receptores do LH/antagonistas & inibidores , Esteroide Isomerases/antagonistas & inibidores , Testículo/efeitos dos fármacos , Testículo/metabolismo
13.
Pharmacology ; 105(7-8): 397-404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31865316

RESUMO

AIMS: Taxifolin, a flavonoid, has several pharmacological activities. Taxifolin inhibits some steroid biosynthetic enzymes, suggesting that it might inhibit neurosteroid synthesis. Here, we investigated effects of taxifolin on rat neurosteroidogenic enzymes, steroid 5α-reductase 1 -(SRD5A1), 3α-hydroxysteroid dehydrogenase (AKR1C9), and retinol dehydrogenase 2 (RDH2). METHODS: SRD5A1, AKR1C9, and RDH2 were expressed in COS-1 cells and the direct effects of taxifolin on these enzymes and the mode of action were determined using steroid substrates and thin chromatography separation-coupled radiometric scanning. RESULTS: The half maximal inhibitory concentration values of taxifolin on SRD5A1 and AKR1C9 were 100 and 1.01 mol/L. Taxifolin did not inhibit RDH2 even at as high as 100 mol/L. Taxifolin competitively inhibited rat AKR1C9 against steroid dihydrotestosterone (DHT), and docking analysis revealed that taxifolin bound to the steroid binding site of rat AKR1C9 with similar free energy with the substrate DHT. CONCLUSION: Taxifolin is a potent inhibitor of rat AKR1C9 and moderate inhibitor of rat SRD5A1, thereby controlling the rate of neurosteroid biosynthesis.

14.
Chemosphere ; 241: 125036, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31606569

RESUMO

Dimethoate is an organophosphate pesticide. It is widely used in agriculture. However, whether it blocks pubertal development of Leydig cells remains unknown. In the current study, we exposed male Sprague Dawley rats with 7.5 and 15 mg kg-1 dimethoate from postnatal day 35-56. We also exposed Leydig cells isolated from 35-day-old rats for 3 h. Dimethoate reduced serum testosterone levels at 7.5 and 15 mg kg-1 but increased serum luteinizing hormone and follicle stimulating hormone levels at 15 mg kg-1. Dimethoate did not influence Leydig cell number but reduced Leydig cell size and down-regulated Star, Cyp11a1, and Hsd3b1 in Leydig cells as well as their protein expression. Dimethoate inhibited basal androgen output in a dose-dependent manner with the inhibition starting at 0.05 µM. It significantly inhibited luteinizing hormone and 8Br-cAMP stimulated androgen outputs at 50 µM. It significantly inhibited 22R-hydroxycholesterol and progesterone-mediated androgen outputs at 50 µM. Further study demonstrated that dimethoate also down-regulated the expression of Star, Cyp11a1, and Hsd3b1 at 5 or 50 µM in vitro. Dimethoate did not directly inhibit rat testicular steroidogenic enzyme activities at 50 µM. In conclusion, dimethoate targets Star, Cyp11a1, and Hsd3b1 transcription, thus blocking Leydig cell differentiation during puberty.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Dimetoato/farmacologia , Células Intersticiais do Testículo/citologia , Puberdade , Androgênios/metabolismo , Animais , Inseticidas/farmacologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Complexos Multienzimáticos/genética , Fosfoproteínas/genética , Progesterona Redutase/genética , Ratos , Ratos Sprague-Dawley , Esteroide Isomerases/genética , Testosterona/sangue , Transcrição Genética
15.
Front Pharmacol ; 10: 1309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780936

RESUMO

Male fetal Leydig cells in the testis secrete androgen and insulin-like 3, determining the sexual differentiation. The abnormal development of fetal Leydig cells could lead to the reduction of androgen and insulin-like 3, thus causing the male reproductive tract anomalies in male neonates, including cryptorchidism and hypospadias. Environmental pollutants, such as phthalic acid esters (phthalates), can perturb the development and differentiated function of Leydig cells, thereby contributing to the reproductive toxicity in the male. Here, we review the epidemiological studies in humans and experimental investigations in rodents of various phthalates. Most of phthalates disturb the expression of various genes encoded for steroidogenesis-related proteins and insulin-like 3 in fetal Leydig cells and the dose-additive effects are exerted after exposure in a mixture.

16.
Environ Pollut ; 255(Pt 2): 113316, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31610511

RESUMO

Paraquat is a fast and non-selective herbicide that is widely used in crop cultivation and conservation tillage systems. Animal experiments have shown that paraquat decreases sperm quality and testicular organ coefficient, but its effects on the development of Leydig cells remain unclear. The objective of the current study was to investigate the effects of paraquat exposure on the Leydig cell development in rats during puberty. Twenty-eight male 35-day-old Sprague-Dawley rats were divided into 4 groups: 0, 0.5, 2.0, and 8 mg kg-1 d-1 paraquat. Paraquat was gavaged for 10 d. Adult Leydig cells were isolated and treated with paraquat for 24 h. Paraquat in vivo significantly decreased body and testis weights at 8 mg kg-1 and lowered serum testosterone levels at 2 and 8 mg kg-1 without affecting the levels of serum luteinizing hormone and follicle-stimulating hormone. Paraquat did not alter Leydig cell number and PCNA labeling index. Real-time PCR showed that paraquat down-regulated the expression of Lhcgr, Scarb1, Cyp11a1, Cyp17a1, and Hsd17b3 genes and their proteins at 2 or 8 mg kg-1, while it up-regulated the expression of Srd5a1 at 8 mg kg-1. Paraquat increased ROS and decreased testosterone production by Leydig cells at 1 and 10 µM after in vitro 24-h exposure. Vitamin E (40 µg/ml) reversed paraquat-induced ROS and suppression of testosterone synthesis in vitro. In conclusion, paraquat directly delays Leydig cell differentiation to block testosterone synthesis via down-regulating the expression of critical testosterone synthesis-related genes and up-regulating the expression of testosterone metabolic enzyme (Srd5a1) gene and possibly via increasing ROS production.


Assuntos
Herbicidas/toxicidade , Células Intersticiais do Testículo/efeitos dos fármacos , Paraquat/toxicidade , Animais , Diferenciação Celular/efeitos dos fármacos , Regulação para Baixo , Hormônio Foliculoestimulante/sangue , Herbicidas/metabolismo , Hormônio Luteinizante/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Maturidade Sexual , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/efeitos dos fármacos , Testosterona/sangue , Regulação para Cima
17.
Front Pharmacol ; 10: 1100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611792

RESUMO

Background: Childhood leukemia is one of the most common cancers in children. As a potential treatment for leukemia, immunotherapy has become a new research hotspot. This research aimed at exploring the status and trends of current researches on immunotherapy for childhood leukemia through bibliometric analysis. Methods: The Institute for Scientific Information Web of Science core collection database was searched for articles on immunotherapy and childhood leukemia using a computer. Time period for retrieval was from the beginning of the database to June 15, 2019. The top 100 highly cited articles were selected to extract their information on publication year, authors, title, publication journal, number of citations, author's affiliations, country, and so on. These general information and bibliometric data were collected for analysis. VOSviewer software was used to generate a figure for keywords' co-occurrence network and a figure for researcher's coauthorship network that visualized reference and cooperation patterns for different terms in the 100 articles. Results: The number of citations in the top 100 articles ranged from 17 to 471. These articles were published in 52 different publications. The top four journals in terms of the number of our selected articles were Leukemia (11 articles), Blood (10 articles), Bone Marrow Transplantation (6 articles), and Clinical Cancer Research. The most frequently nominated author was T. Klingebiel from Goethe University Frankfurt, and of the top 100 articles, 12 listed his name. These top 100 articles were published after the year 2000. Most of these articles were original (67%). The United States and Germany were the major countries researching immunotherapy for childhood leukemia and made significant contributions to the combat against the disease. Adoptive immunotherapy and stem cell transplantation appeared more frequently in keywords. Conclusions: This study analyzed the top 100 highly cited articles on immunotherapy for childhood leukemia and provided insights into the features and research hotspots of the articles on this issue.

18.
Chem Biol Interact ; 312: 108817, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499053

RESUMO

Aconitine might have reproductive toxicity and the effects of aconitine on androgen synthesis in Leydig cells remain unclear. Here, we explore how aconitine affects androgen synthesis and metabolism in rat immature Leydig cells in vitro. Immature Leydig cells were isolated from 35-day-old male Sprague Dawley rats and cultured with 0-50 µM aconitine for 3 h in combination with LH, 8Br-cAMP, 22R-hydroxycholesterol, pregnenolone, progesterone, androstenedione, testosterone, and dihydrotestosterone, respectively. Medium androgens were measured. The levels of Leydig cell mRNAs, Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Srd5a1, and Akr1c14, were measured by qPCR. ROS and apoptosis were determined after 24-h aconitine treatment. Aconitine inhibited basal androgen production in Leydig cells at 0.05 µM and the higher concentrations. Aconitine blocked pregnenolone, progesterone, and androstenedione mediated androgen outputs without affecting 22R-hydroxycholesterol-mediated androgen production at 5 µM. Aconitine also inhibited LH and 8Br-cAMP stimulated androgen outputs at 5 µM. Further investigation showed that aconitine blocked androgen synthesis via down-regulating the expression of Scarb1, Hsd3b1, Cyp17a1, and Hsd17b3. At 50 µM, aconitine also induced ROS generation and increased apoptotic rate of Leydig cells. Aconitine lowered serum testosterone levels at 1.5 mg/kg after 7 days of oral exposure from postnatal day 35. In conclusion, aconitine inhibits androgen synthesis.


Assuntos
Aconitina/farmacologia , Androgênios/metabolismo , Regulação para Baixo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores do LH/genética , Receptores do LH/metabolismo , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismo , Testosterona/sangue , Testosterona/farmacologia
19.
Chem Res Toxicol ; 32(9): 1772-1779, 2019 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-31423765

RESUMO

Polybrominated diphenyl ethers (PBDEs) are a group of flame retardants with two or more bromines attached. They are endocrine disruptors. PBDEs photodegrade into 4-bromodiphenyl ether (BDE3). Whether BDE3 impairs adrenal cortical cell function during postnatal development still remains unknown. The aim of the current study was to investigate the influence of BDE3 on adrenal cortical cell function. Sprague-Dawley rats (35 days of age, male) were orally administered with BDE3 (0, 50, 100, and 200 mg/kg/day body weight) for 21 days. BDE3 significantly increased serum aldosterone and corticosterone levels at 200 mg/kg without affecting adrenocorticotropic hormone level. Further study showed that BDE3 up-regulated Cyp11b1 at 100 and 200 mg/kg and Scarb1, Star, Cyp11b2, Cyp21, and Nr5a1 mRNA levels in the 200 mg/kg group. BDE3 also decreased the phosphorylation of AMP-activated protein kinase (AMPK) at 200 mg/kg and increased PGC-1α and phosphorylated cyclic AMP-responsive element-binding protein (CREB)/CREB at 200 mg/kg. Taken together, these findings demonstrate that BDE3 stimulates adrenal cell function likely through decreasing phosphorylation of AMPK and increasing phosphorylation of CREB.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Éteres Difenil Halogenados/toxicidade , Puberdade/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/química , Proteínas Quinases Ativadas por AMP/metabolismo , Aldosterona/metabolismo , Animais , Corticosterona/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/química , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Puberdade/metabolismo , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
20.
Toxicology ; 425: 152253, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351905

RESUMO

Human placental 3ß-hydroxysteroid dehydrogenase/steroid Δ5, 4-isomerase 1 (HSD3B1), a high-affinity type I enzyme, uses pregnenolone to make progesterone, which is critical for maintenance of pregnancy. HSD3B1 is located in the mitochondrion and the smooth endoplasmic reticulum of placental cells and is encoded by HSD3B1 gene. HSD3B1 contains GATA and TEF-5 regulatory elements. Many endocrine disruptors, including phthalates, methoxychlor and its metabolite, organotins, and gossypol directly inhibit placental HSD3B1 thus blocking progesterone production. In this review, we discuss the placental HSD3B1, its gene regulation, biochemistry, subcellular location, and inhibitors from the environment.


Assuntos
Complexos Multienzimáticos/metabolismo , Placenta/enzimologia , Progesterona Redutase/metabolismo , Esteroide Isomerases/metabolismo , Poluentes Ambientais/efeitos adversos , Feminino , Regulação da Expressão Gênica , Humanos , Complexos Multienzimáticos/antagonistas & inibidores , Complexos Multienzimáticos/química , Complexos Multienzimáticos/genética , Placenta/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Progesterona Redutase/antagonistas & inibidores , Progesterona Redutase/química , Progesterona Redutase/genética , Esteroide Isomerases/antagonistas & inibidores , Esteroide Isomerases/química , Esteroide Isomerases/genética
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