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1.
Gen Comp Endocrinol ; 286: 113306, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31669651

RESUMO

Mechanistic target of rapamycin complex 1 (mTORC1) plays crucial roles in male fertility. In mammals, deregulation of mTORC1 led to disordered spermatogonia proliferation and spermatogenesis, which eventually caused infertility in males. However, its roles in male fertility of non-mammalian species remain unclarified. In the present study, it was found that treatment of rapamycin, an mTORC1 inhibitor, resulted in infertility with decreased milt production and sperm motility in zebrafish. However, it is surprising to find that spermatogenesis was normal in these fish. All types of germ cells were found and the proliferation of spermatogonia and spermatocyte were normal. These results suggested that maturation of sperm may be impaired in males treated with rapamycin. Increased apoptosis was found surrounding the lumen containing spermatozoa, implicating a loss of Sertoli cells in testes treated with rapamycin. Moreover, LH/hCG mediated up-regulation of steroidogenic genes was abolished. The expression of npr and ar induced by LH/hCG was also blocked, which further suppressed the signaling of progestin and androgen. Collectively, mTORC1 maintains male fertility via different mechanisms in fish and mammals. mTORC1 is dispensable for spermatogenesis in zebrafish, but possibly supports the maintenance of Sertoli cells and mediates the signaling of hormones, which are crucial for sperm maturation.

2.
Sci Rep ; 9(1): 14021, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575998

RESUMO

We aimed to assess the ulcer healing time and recurrence rates after treatment with compression therapy (CT) with or without high ligation-endovenous laser ablation-foam sclerotherapy (HL-EVLA-FS) in people with active venous leg ulcers (VLUs). A retrospective cohort study was conducted with 350 patients with active VLUs treated by compression with or without HL-EVLA-FS in our hospital from 2013 to 2017. The primary outcome was the ulcer healing time; secondary outcomes were the 12-month recurrence rates, the relationship between recurrence and venous reflux, and the complications of the two treatments. In total, 193 patients (200 limbs) underwent compression plus HL-EVLA-FS, and 157 patients (177 limbs) underwent CT alone. The ulcer healing time was shorter in the compression plus HL-EVLA-FS group than in the CT alone group (Hazard Ratio [HR] for ulcer healing, 1.845 [95% CI, 1.474-2.309], P = 0.0001). The 12-month ulcer recurrence rates were significantly reduced in the compression plus HL-EVLA-FS group (HR for ulcer recurrence, 0.418 [95% CI, 0.258-0.677], P = 0.0001). Calf perforator vein reflux (CPVR) and isolated superficial venous reflux (ISVR) were risk factors for ulcer recurrence. The combined operation with CT resulted in faster healing of VLUs, a lower ulcer recurrence rate and lower VCSS values after intervention than CT alone.

3.
Opt Express ; 27(16): A995-A1003, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510488

RESUMO

The excited-state carrier dynamics of lead halide perovskites play a critical role in their photoelectric properties, and are greatly affected by lattice structural changes. In this work, the carrier dynamics of all-inorganic CsPbBr3 peroveskite, as a function of pressure, are investigated using in situ high-pressure femtosecond transient absorption spectroscopic experiments. Compression is found to drive crystal structural evolution, thereby markedly changing the behavior of charge carriers in CsPbBr3. Before the phase transition, simultaneous prolonging of the carrier relaxation and Auger recombination is achieved alongside a narrowing in the bandgap. The results favor improved efficiency and photovoltaic performance.

4.
Medicine (Baltimore) ; 98(37): e17010, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517820

RESUMO

PURPOSE: To find out whether the intramedullary fixations are superior to the extramedullary fixations in treating unstable femoral intertrochanteric fractures (UFIFs). METHODS: The meta-analysis of randomized controlled trials (RCTs) was conducted by searching the PubMed, Cochrane Library, and Embase databases to evaluate functional scores, surgical outcomes, and adverse events in adult patients receiving intramedullary fixations in comparison to extramedullary fixations. Risk ratio (RR) or weighted mean difference (WMD)/standard mean difference (SMD) with 95% confidence intervals (CIs) were calculated as effect sizes. RESULTS: A total of 18 RCTs, comprising 2414 patients, were included in this meta-analysis. Primary efficacy outcome: Parker scores [weighted mean difference, 1.10, 95% confidence interval (CI), 0.64-1.55; P < .0001] and Harris hip scores [risk ratio, 1.24, 95%CI, 1.09 -1.41; P = .0008] were higher in the intramedullary fixation group. Moreover, blood loss, operative time, length of incision, hospital stay, and implant failure were superior in the intramedullary fixation group. Other secondary efficacy outcome: No significant differences were found between the 2 groups in terms of fluoroscopy time, mortality, cut-out, nonunion, superficial wound infection, later fracture, and reoperation. CONCLUSIONS: This meta-analysis suggested that intramedullary fixation is more effective and safer than extramedullary fixation in treating UFIFs. Furthermore, blood loss, operative time, length of incision, hospital stay, and implant failure were superior in the intramedullary fixation group.


Assuntos
Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/métodos , Humanos , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Mar Biotechnol (NY) ; 21(5): 707-717, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392592

RESUMO

The giant grouper, Epinephelus lanceolatus, is the largest coral reef-dwelling bony fish species. However, despite extremely fast growth performance and the considerable economic importance in this species, its genetic regulation of growth remains unknown. Here, we performed the first genome-wide association study (GWAS) for five growth traits in 289 giant groupers using 42,323 single nucleotide polymorphisms (SNPs) obtained by genotyping-by-sequencing (GBS). We identified a total of 36 growth-related SNPs, of which 11 SNPs reached a genome-wide significance level. The phenotypic variance explained by these SNPs varied from 7.09% for body height to 18.42% for body length. Moreover, 22 quantitative trait loci (QTLs) for growth traits, including nine significant QTLs and 13 suggestive QTLs, were found on multiple chromosomes. Interestingly, the QTL (LG17: 6934451) was shared between body weight and body height, while two significant QTLs (LG7: 22596399 and LG15: 11877836) for body length were consistent with the associated regions of total length at the genome-wide suggestive level. Eight potential candidate genes close to the associated SNPs were selected for expression analysis, of which four genes (phosphatidylinositol transfer protein cytoplasmic 1, protein tyrosine phosphatase receptor type E, alpha/beta hydrolase domain-containing protein 17C, and vascular endothelial growth factor A-A) were differentially expressed and involved in metabolism, development, response stress, etc. This study improves our understanding of the complex genetic architecture of growth in the giant grouper. The results contribute to the selective breeding of grouper species and the conservation of coral reef fishes.

6.
J Invest Dermatol ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31425706

RESUMO

Atopic dermatitis (AD) is often concomitant with increased levels of IgE against not only foreign allergens but also autoallergens. AD patients with autoallergy are likely to be more severe and difficult to treat, and self-reactive IgE might be a contributing factor in the pathogenesis of AD. However, how autoallergens are recognized by the immune system and what immune responses are induced subsequently remain largely unknown. We found that the serum level of IgE against transglutaminase 3 (TGase3) was significantly higher in AD patients than in healthy individuals and was positively correlated with disease severity. The expression of TGase3 in the lesional skin of AD patients was markedly increased compared with that of the controls, and Th2 cytokines and/or allergen promoted the expression of TGase3 in keratinocytes. TGase3 bond monocytes-derived dendritic cells (MoDCs) via dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), which resulted in the production of IL-6 and activation of the NF-κB signaling pathway in MoDCs; and TGase3-treated MoDCs facilitated Th1 polarization. Moreover, skin inflammation in the mouse model of MC903-induced AD was attenuated when TGase3 was inhibited. In conclusion, TGase3 was revealed as an autoallergen in AD and actively involved in skin inflammation; TGase3-targeting might be a therapeutic strategy for the treatment of AD.

7.
Nature ; 572(7771): 620-623, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31384042

RESUMO

Non-line-of-sight imaging allows objects to be observed when partially or fully occluded from direct view, by analysing indirect diffuse reflections off a secondary relay surface. Despite many potential applications1-9, existing methods lack practical usability because of limitations including the assumption of single scattering only, ideal diffuse reflectance and lack of occlusions within the hidden scene. By contrast, line-of-sight imaging systems do not impose any assumptions about the imaged scene, despite relying on the mathematically simple processes of linear diffractive wave propagation. Here we show that the problem of non-line-of-sight imaging can also be formulated as one of diffractive wave propagation, by introducing a virtual wave field that we term the phasor field. Non-line-of-sight scenes can be imaged from raw time-of-flight data by applying the mathematical operators that model wave propagation in a conventional line-of-sight imaging system. Our method yields a new class of imaging algorithms that mimic the capabilities of line-of-sight cameras. To demonstrate our technique, we derive three imaging algorithms, modelled after three different line-of-sight systems. These algorithms rely on solving a wave diffraction integral, namely the Rayleigh-Sommerfeld diffraction integral. Fast solutions to Rayleigh-Sommerfeld diffraction and its approximations are readily available, benefiting our method. We demonstrate non-line-of-sight imaging of complex scenes with strong multiple scattering and ambient light, arbitrary materials, large depth range and occlusions. Our method handles these challenging cases without explicitly inverting a light-transport model. We believe that our approach will help to unlock the potential of non-line-of-sight imaging and promote the development of relevant applications not restricted to laboratory conditions.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 222: 117244, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31203054

RESUMO

Excited-state deactivation dynamics of Thioflavin-T (ThT) in gradual viscosity solvents were investigated. Femtosecond transient absorption spectra and dynamic decay curves both present significant distinction of ThT in different volume ratios binary mixtures solvents. Dynamics fitting lifetime of twisted intramolecular charge transfer (TICT) state is strongly dependent on solvents viscosity. Compared to rotation corresponding time of ThT in low viscosity solvent (0.6 cp) experimentally coincident well with Stokes-Einstein-Debye (SED) equation, the relation between rotation corresponding time and relatively high viscosity (5.9 cp to 1091.2 cp) is more consistent with fractional SED equation. Combined with optimized geometric structures of ThT by density functional theory and time-dependent density functional theory, further understand TICT state lifetime increases with increasing solvents viscosity. Our work provides a comprehensive understanding of fluorescence molecular rotor (FMR) deactivation process in different viscosity solvents and is helpful to design new FMR.

9.
J Phys Chem Lett ; 10(11): 3064-3070, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31120761

RESUMO

Electron transfer (ET) and Auger recombination (AR) processes in quantum dots (QDs) are key mechanisms for the advance of QD-based devices. However, it still remains a challenge to promote ET and suppress AR simultaneously. Here, we use in situ high-pressure ultrafast transient absorption spectroscopy to explore the impact of pressure on the ET between CdSe/ZnS and anthraquinone (AQ) and AR dissolved in cyclohexane. Remarkably, under compression, ET lifetimes are shorten, while suppression of AR lifetimes is present. The promotion of ET is attributed to the shortened distance between CdSe/ZnS and AQ induced by pressure. We rationalize that for the AR suppression, pressure may enhance the formation of an alloy layer at the core/shell interface. These findings indicate that compression is an effective approach to promote ET and suppress AR simultaneously. This study highlights a brand-new approach for modulating ET and AR and provides new routes toward QD-based applications.

10.
Int J Biol Macromol ; 133: 457-465, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31002905

RESUMO

This study, for the first time in fish, compared the transcriptome of fresh and frozen-thawed sperm, and would help to better understand the effect of cryopreservation on fish sperm and then better preserve the aquatic germplasm resources. Here, we employed high-throughput sequencing technology to obtain the transcriptome of yellow catfish from fresh sperm, cryopreserved sperm with and without cryoprotectant. When cryoprotectant (Me2SO) was excluded, down-regulated genes were significantly enriched into calcium ion binding, cytoskeletal protein binding, microfilament motor activity, calmodulin binding and carnitine O-acyltransferase activity, which affected Ca2+ regulation, cellular morphology, motility and metabolism. Moreover, heat shock proteins and genes associated with regulation of cholesterol, HCO3- and protein tyrosine phosphorylation (PTP) were down-regulated, and thus would impair ability against stress, membrane rigidity, pH regulation and signal transduction of cryopreserved sperm. After Me2SO was added, the amounts of DEGs decreased significantly and down-regulation of genes were found mainly in cytoskeleton and heat shock proteins, thereby suggesting that Me2SO effectively reduced the impact caused by low temperature on gene expression. Whether adding Me2SO or not, the up-regulated genes were mainly found in ribosomal proteins genes. However, when Me2SO was added, over-expression of some genes might contribute to maintain normal function of cryopreserved sperm.


Assuntos
Peixes-Gato/genética , Criopreservação , Crioprotetores/farmacologia , Dimetil Sulfóxido/farmacologia , Perfilação da Expressão Gênica , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Animais , Masculino
11.
Allergy ; 74(9): 1738-1747, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30964950

RESUMO

BACKGROUND: Epicutaneous sensitization is an important route of immunization for allergens in atopic diseases; however, studies have also shown that application with protein on the intact skin induces antigen-specific tolerance. Langerhans cells (LCs) play an immunosuppressive role in several inflammatory skin diseases and mouse models, and the role of LCs in the skin-induced tolerance is not fully understood. METHODS: Langerin-DTA mice that were deficient in LCs were utilized to produce the model of skin-induced tolerance to ovalbumin (OVA). Binding of Langerin to OVA was analyzed by enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence. Homozygous Langerin-DTR mice that were deficient in Langerin were introduced to assess the role of Langerin in the skin-induced tolerance. RESULTS: Application with OVA onto the intact, but not tape-stripped, skin attenuated the production of OVA-specific IgE, IgG1, and IgG2a induced by subsequent subcutaneous immunization with OVA, and the inhibitory effects were abolished in Langerin-DTA mice. In contrast to the tape-stripped skin, the intact skin induced the production of IL-10 by LCs in draining lymph node after application with OVA. Langerin could bind OVA, and homozygous Langerin-DTR mice demonstrated similar humoral and cellular immune responses in the model of skin-induced tolerance compared to wide-type mice. CONCLUSION: Our data suggested that LCs were critical in the intact skin-induced tolerance to protein antigen via Langerin, and LCs might be targeted via Langerin to regulate the immune responses in systemic and (or) skin inflammatory diseases.

12.
Gene ; 700: 120-130, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-30910559

RESUMO

Stem-loop binding protein (SLBP) binds a stem-loop structure of the mRNA, which is important for the stability of histone mRNAs and translation process. In the present study, two slbp cDNAs (Ecslbp1 and Ecslbp2) were cloned from a protogynous hermaphroditic orange-spotted grouper, Epinephelus coioides. Ecslbp1 cDNA contained a 678 base pair (bp) open reading frame (ORF), encoding a predicted polypeptide of 225 amino acids. Ecslbp2 cDNA contained a 1041 bp, encoding a predicted protein of 346 amino acids. The result of real-time PCR revealed that Ecslbp2 mRNA was exclusively detected in the ovary. Moreover, it was found to be restricted to oocytes according to in situ hybridization (ISH) analysis. Ecslbp2 was found to be hardly detected in gonia and significantly increase in the cytoplasm of primary-growth stage oocytes, but decreased during the process of vitellogenesis. Interestingly, Ecslbp2 expression centralized as a perinuclear speckle in early-primary-growth stage oocytes, which appeared to form into the Balbiani body (Bb) in late-primary-growth stage oocytes. These data indicated that Ecslbp2 might play an important role in the process of oocyte development, and could serve as an oocyte-specific molecular marker for the study of ovary development and sex reversal in groupers.


Assuntos
Bass/fisiologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Processos de Determinação Sexual , Animais , Bass/genética , Bass/metabolismo , Clonagem Molecular , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Fases de Leitura Aberta , Especificidade de Órgãos , Ovário/crescimento & desenvolvimento , Ovário/metabolismo
13.
J Steroid Biochem Mol Biol ; 189: 10-18, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30711474

RESUMO

Estrogens exert their biological functions through the estrogen receptors (ERs). In zebrafish, three nuclear estrogen receptors (nERs) named ERα, ERß1 and ERß2 and one membrane-bound G protein-coupled estrogen receptor (GPER) are identified. Vitellogenin (Vtg) is predominantly expressed in liver and strongly response to the stimulation of estrogen. It has been proposed that all three nERs are functionally involved in vitellogenesis and ERα may act as the major mediator in teleost. However, the role of GPER and its interaction with nERs in this process are not yet defined in teleost species. In the present study, we provide genetic evidence for the functional significance of ERα that the expression of Vtg genes (vtg1, vtg2, vtg3) and their response to estradiol stimulation were significantly decreased in esr1 mutant zebrafish. Activation of ERß1 and ERß2 induced Vtg expression through ERα. Moreover, the involvement of GPER in vitellogenesis and its interaction with nERs in zebrafish were firstly proposed in this work. Activation of GPER induced Vtg genes expression while inhibition of GPER significantly attenuated the estrogenic effect on Vtg. Both treatments altered the expression levels of nERs, suggesting GPER acts interactively with nERs. Collectively, the involvement of both nERs and GPER in regulation of vitellogenesis is demonstrated. ERα is the central factor, acting interactively with ERß1, ERß2 and GPER, and GPER regulates vitellogenesis directly and interactively with nERs.

14.
J Phys Chem Lett ; 10(4): 748-753, 2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30704239

RESUMO

The twisted intramolecular charge transfer (TICT) state plays an important role in determining the performance of optoelectronic devices. However, for some nonfluorescent TICT molecules, the "invisible" TICT state could only be visualized by modifying the molecular structure. Here, we introduce a new facile pressure-induced approach to light up the TICT state through the use of a pressure-related liquid-solid phase transition of the surrounding solvent. Combining ultrafast spectroscopy and quantum chemical calculations, it reveals that the "invisible" TICT state can emit fluorescence when the rotation of a donor group is restricted by the frozen acetonitrile solution. Furthermore, the TICT process can even be effectively regulated by the external pressure. Our study offers a unique strategy to achieve dual fluorescence behavior in charge transfer molecules and is of significance for optoelectronic and biomedical applications.

15.
J Invest Dermatol ; 139(8): 1779-1787.e12, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30802424

RESUMO

Previous studies have shown independently that the skin and gut microbiota are closely associated with atopic dermatitis (AD); however, the microbiota across different habitats of AD patients as an integrated community has not been characterized. In the present study, we comparatively analyzed the structure and function of the microbial communities in the skin, oral cavity, and gut of 172 AD patients and 120 healthy controls through 16S ribosomal RNA gene amplicon sequencing. The skin and oral cavity, but not the gut, of AD patients demonstrated differential reduction in the microbial diversity, and these were distinctly correlated with disease severity. Different degrees of shifts in the community structure were found among different habitats, and the lineage distance between the skin and oral microbiota of AD patients was closer than that observed in the controls. The different habitats of AD patients exhibited site-specific alterations at the genus level, and many oral-specific microbes of AD showed opposing directions of enrichment in the skin and oral cavity. Most interestingly, an inverse association in the functional pathways was found between the skin and oral microbiota of AD patients. Additionally, the alterations of the microbiota in different body sites of AD patients were differentially affected by age.

16.
Medicine (Baltimore) ; 98(5): e14389, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702633

RESUMO

Venous leg ulcers (VLUs) are an important health problem, and the size of ulcers often affects patient care, healing time, and quality of life. However, the risk factors associated with ulcer size have been rarely reported. The aim of this study was to establish the risk factors for the size of venous ulceration by analyzing the patient demographics and the results of duplex ultrasonography.This study was an in-patient population-based cross-sectional study conducted at a single center during the period from 2013 to 2017. Men and women aged >18 years, who consecutively presented to our hospital with VLU, were included. According to the size of the ulcer, patients were divided into two groups, those with ulcers≤2 cm and those with ulcers >2 cm. Demographic, anthropometric, and clinical data were collected. For the analysis, univariate and multivariate logistic regressions were used.A total of 232 patients with VLUs were admitted to our hospital from 2013 to 2017, including 117 patients (50.4%) with ulcer diameters ≤2 cm and 115 patients (49.6%) with ulcer diameters >2 cm. According to the results of the multivariate analysis, the ulcer duration (P = .001), the diameter of perforating veins (PVs) around the ulcers (P = .025), the reflux time of common femoral veins (CFVs) (P = .013), the reflux time of great saphenous veins (GSVs) (P = .021), and the reflux time of PVs around the ulcers (P = .001) were independent risk factors for VLUs.These findings provide evidence that the size of VLU was significantly related to the ulcer duration, the diameter of PV around the ulcers, the CFV reflux time, the GSV reflux time, and the PV reflux time.


Assuntos
Úlcera Varicosa/patologia , Adulto , Idoso , Estudos Transversais , Feminino , Veia Femoral/fisiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Veia Safena/fisiologia , Fatores Sexuais , Ultrassonografia , Úlcera Varicosa/diagnóstico por imagem , Úlcera Varicosa/epidemiologia
17.
Chemosphere ; 221: 235-245, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30640006

RESUMO

Bisphenol A (BPA) is an abundant endocrine-disrupting compound that is found in the aquatic environment and has adverse effects on fish reproduction; however, the exact pathway of these impacts is unclear. In this study, the different effects of BPA on ovarian and testis development in goldfish (Carassius auratus) and the different mechanisms underlying these effects were investigated. The gonadosomatic index (GSI) and gonadal histology demonstrated that BPA diminished ovarian maturation in goldfish, which recovered after BPA treatment withdrawal. In males, BPA disrupted testis maturation, but this disruption could not be recovered after BPA treatment withdrawal. The hypothalamic-pituitary-gonad (HPG) axis-related genes sgnrh, fshß and lhß were significantly decreased in BPA-treated female fish, while no changes in sex steroid hormone levels and no TUNEL and PCNA staining were found in the ovary, suggesting that BPA may reduce ovarian maturation through the HPG axis. In male fish, TUNEL staining was found in 1 µg L-1 BPA-exposed germ cells and 50 and 500 µg L-1 BPA-exposed Leydig cells. Decreases in 11-KT levels were also found in 50 and 500 µg L-1 BPA-exposed fish, but BPA did not affect genes associated with the HPG axes. This result shows that BPA disrupts testis maturation through apoptosis of germ cells and Leydig cells, thus inducing decreases in 11-KT levels that disrupt spermatogenesis. Collectively, our findings provide insights into the molecular and cellular mechanisms underlying BPA disturbance of goldfish reproduction.


Assuntos
Compostos Benzidrílicos/toxicidade , Carpa Dourada/crescimento & desenvolvimento , Gônadas , Fenóis/toxicidade , Reprodução/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Feminino , Células Germinativas/citologia , Carpa Dourada/metabolismo , Gônadas/efeitos dos fármacos , Células Intersticiais do Testículo/citologia , Masculino , Ovário/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
18.
Gen Comp Endocrinol ; 274: 26-36, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30594589

RESUMO

The orange-spotted grouper, Epinephelus coioides, is a marine protogynous hermaphrodite fish of commercial importance. There are many examples of sex change species among marine fish, but the molecular basis for the sex change is still unknown. Gonadal expression patterns of the dmrts and foxls genes in E. coioides have pointed to sexual dimorphism in this species and it has been shown that mRNA levels of dmrts and foxls to vary significantly during reproduction cycles. The steroid 17α-methyltestosterone was used to induce sex reversal in these fish, during which dmrts and foxls levels changed significantly and subsequently reverted to normal when 17α-methyltestosterone was withdrawn. Interestingly, the expression of dmrt2b and dmrt3 was not affected by this steroid. We speculate that the role of foxl2 in reproduction may be conserved via regulation of early differentiation of the ovary by the hypothalamus-pituitary-gonad axis, and dmrt2 may have a significant role in premature ovarian differentiation and maintenance in E. coioides. dmrt1 and foxl3 played a role in the development of the testes and are believed to be potential male regulatory genes.


Assuntos
Bass/genética , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gônadas/embriologia , Gônadas/metabolismo , Metiltestosterona/farmacologia , Processos de Determinação Sexual/efeitos dos fármacos , Animais , Sequência de Bases , Bass/metabolismo , DNA Complementar/genética , Feminino , Proteínas de Peixes/metabolismo , Gônadas/efeitos dos fármacos , Masculino , Ovário/efeitos dos fármacos , Ovário/metabolismo , Filogenia , RNA Mensageiro/genética , Testículo/efeitos dos fármacos , Testículo/metabolismo , Distribuição Tecidual/efeitos dos fármacos
19.
Bioorg Med Chem Lett ; 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30501963

RESUMO

A series of our previously described BH3 peptide mimetics derived from Bim-BH3 domain core region were found to exhibit weak to potent PTP1B binding affinity and inhibitory activities via target-based drug screening. Among these compounds, a 12-aa Bim-BH3 core sequence peptide conjugated to palmitic acid (SM-6) displayed good PTP1B binding affinity (KD = 8.38 nmol/L), inhibitory activity (IC50 = 1.20 µmol/L) and selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). Furthermore, SM-6 promoted HepG2 cell glucose uptake and inhibited the expression of PTP1B, indicating that SM-6 could improve the insulin resistance effect in the insulin-resistant HepG2 cell model. These results may indicate a new direction for the application of BH3 peptide mimetics and promising PTP1B peptide inhibitors could be designed and developed based on SM-6.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30319547

RESUMO

It is well established that estrogens regulate female reproduction through estrogen receptors (ERs) in the ovary. However, the precise physiological role of estrogen/ER signaling in reproduction processes remains poorly defined in zebrafish. In this study, we successfully generated an ERα (esr1) mutant line in zebrafish via transcription activator-like effectors nucleases (TALENs). It was found in the mutant females that the fertility was enhanced and the ovarian histology was normal at 90 days post-fertilization (dpf). However, the number of fertile females decreased with age. By 180 dpf, esr1 mutant females were infertile with degenerated ovaries, while the age-matched wild-type females were still fertile. Additionally, few large vitellogenic granules can be found in full grown (FG) follicles at 90 dpf and the expression of vtg genes were down-regulated at both 90 and 180 dpf in esr1 mutant zebrafish. Moreover, steroidogenesis pathway and mTOR signaling pathway were over-activated at 90 dpf, but declined prematurely in esr1 mutant zebrafish by 180 dpf. Collectively, the present study provides evidence that esr1 is fundamental for ovarian maintenance in zebrafish.

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