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1.
Lipids Health Dis ; 23(1): 180, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862993

RESUMO

BACKGROUND: The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. METHODS: Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. RESULTS: A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. CONCLUSIONS: This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.


Assuntos
Autofagia , Barreira Hematotesticular , Bussulfano , Caprilatos , Estresse Oxidativo , Células de Sertoli , Espermatogênese , Masculino , Animais , Barreira Hematotesticular/efeitos dos fármacos , Barreira Hematotesticular/metabolismo , Bussulfano/efeitos adversos , Caprilatos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Humanos , Espermatogênese/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/patologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Adulto
2.
Cell Mol Life Sci ; 79(2): 114, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35103851

RESUMO

Sertoli cells are essential for spermatogenesis in the testicular seminiferous tubules by forming blood-testis barrier (BTB) and creating a unique microenvironment for spermatogenesis. Many lncRNAs have been reported to participate in spermatogenesis. However, the role of long noncoding RNAs (lncRNAs) in Sertoli cells has rarely been examined. Herein, we found that a high-fat diet (HFD) decreased sperm quality, impaired BTB integrity and resulted in accumulation of saturated fatty acids (SFAs), especially palmitic acid (PA), in mouse testes. PA decreased the expression of tight junction (TJ)-related proteins, increased permeability and decreased transepithelial electrical resistance (TER) in primary Sertoli cells and TM4 cells. Moreover, lncRNA Tug1 was found to be involved in PA-induced BTB disruption by RNA-seq. Tug1 depletion distinctly impaired the TJs of Sertoli cells and overexpression of Tug1 alleviated the disruption of BTB integrity induced by PA. Moreover, Ccl2 was found to be a downstream target of Tug1, and decreased TJ-related protein levels and TER and increased FITC-dextran permeability in vitro. Furthermore, the addition of Ccl2 damaged BTB integrity after overexpression of Tug1 in the presence of PA. Mechanistically, we found that Tug1 could directly bind to EZH2 and regulate H3K27me3 occupancy in the Ccl2 promoter region by RNA immunoprecipitation and chromatin immunoprecipitation assays. Our study revealed an important role of Tug1 in the BTB integrity of Sertoli cells and provided a new view of the role of lncRNAs in male infertility.


Assuntos
Barreira Hematotesticular/metabolismo , RNA Longo não Codificante/genética , Túbulos Seminíferos/irrigação sanguínea , Células de Sertoli/metabolismo , Espermatogênese/genética , Junções Íntimas/genética , Animais , Células Cultivadas , Quimiocina CCL2/biossíntese , Quimiocina CCL2/genética , Dieta Hiperlipídica , Impedância Elétrica , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histonas/metabolismo , Infertilidade Masculina/genética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Obesidade/patologia , Ácido Palmítico/análise , Análise do Sêmen , Espermatogênese/fisiologia
3.
BMC Pregnancy Childbirth ; 21(1): 215, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731060

RESUMO

BACKGROUND: China has one of the highest caesarean section (C-Section) rates in the world. In recent years, China has been experiencing a massive flow of migration due to rapid urbanization. In this study, we aimed to differentiate the rates of C-Section between migrants and residents, and explore any possible factors which may moderate the association between migrant status and C-Section rates. METHODS: We conducted a retrospective cohort study in Shanghai, China. All deliveries were classified using the modified Robson Classification. The association between women's migrant status and C-Section rates was assessed using the Poisson regression of sandwich estimation, after adjusting for possible factors. RESULTS: Of the 40,621 women included in the study, 66.9% were residents and 33.1% were internal migrants. The rate of C-Section in migrants was lower than that of residents in all subjects (39.9 and 47.7%) and in group 1 subjects (based on the Robson Classification) using a modified Robson Classification. There was an association between migrant status and caesarean delivery on maternal request that was statistically significant (RR = 0.664, p < 0.001), but the association was weakened after adjusting for such factors as maternal age at delivery (aRR = 0.774, p = 0.02), ethnicity (aRR = 0.753, p < 0.001), health insurance (aRR = 0.755, p < 0.001), and occupation (aRR = 0.747, p = 0.004), but had no significant changes when adjusting for health conditions (aRR = 0.668, p = 0.001) and all considering variables (aRR = 0.697, p = 0.002). In group 1 subjects, the effect of migrant status on maternal requested intrapartum C-Section was also statistically significant (RR = 0.742, p = 0.004). CONCLUSION: C-Section rates are lower among migrant women than residents, especially on maternal request. The medical practitioners should further reinforce the management of elective C-Section in resident women.


Assuntos
Cesárea/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos , Preferência do Paciente/estatística & dados numéricos , Características de Residência , Migrantes/estatística & dados numéricos , Adulto , China/epidemiologia , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Distribuição de Poisson , Gravidez , Estudos Retrospectivos
4.
Open Life Sci ; 19(1): 20220947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290497

RESUMO

The cardiometabolic index (CMI) is an emerging and effective indicator for predicting the presence of metabolic-associated fatty liver disease (MAFLD). This study aims to investigate the relationship between CMI and MAFLD using data from NHANES 2017-2020. In this cross-sectional study, a total of 3,749 subjects were included. The study conducted a thorough analysis of CMI with three multivariate logistic regression models, subgroup analyses, and restricted cubic splines (RCS) were utilized. Using multifactorial logistic regression as the primary method of analysis, we found that a higher CMI was also significantly associated with an increased risk of MAFLD (OR = 1.45, 95% CI (1.05-2.01)). This result was further visualized by the RCS curve: There was a non-linear positive correlation between CMI and MAFLD incidence (the turning point is CMI = 0.4554). These findings were strongly reinforced by subsequent subgroup and sensitivity analyses. There is a robust positive relationship between the CMI and the risk of MAFLD, providing valuable clinical benefits for early detection and screening of MAFLD. It is important to highlight the presence of a non-linear association between CMI and MAFLD, with an inflection point identified at CMI = 0.4554.

5.
IEEE Trans Image Process ; 32: 2093-2106, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37023145

RESUMO

Knowledge amalgamation (KA) is a novel deep model reusing task aiming to transfer knowledge from several well-trained teachers to a multi-talented and compact student. Currently, most of these approaches are tailored for convolutional neural networks (CNNs). However, there is a tendency that Transformers, with a completely different architecture, are starting to challenge the domination of CNNs in many computer vision tasks. Nevertheless, directly applying the previous KA methods to Transformers leads to severe performance degradation. In this work, we explore a more effective KA scheme for Transformer-based object detection models. Specifically, considering the architecture characteristics of Transformers, we propose to dissolve the KA into two aspects: sequence-level amalgamation (SA) and task-level amalgamation (TA). In particular, a hint is generated within the sequence-level amalgamation by concatenating teacher sequences instead of redundantly aggregating them to a fixed-size one as previous KA approaches. Besides, the student learns heterogeneous detection tasks through soft targets with efficiency in the task-level amalgamation. Extensive experiments on PASCAL VOC and COCO have unfolded that the sequence-level amalgamation significantly boosts the performance of students, while the previous methods impair the students. Moreover, the Transformer-based students excel in learning amalgamated knowledge, as they have mastered heterogeneous detection tasks rapidly and achieved superior or at least comparable performance to those of the teachers in their specializations.

6.
Toxicol Lett ; 376: 1-12, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36642205

RESUMO

As a widespread environmental contaminant, short chain chlorinated paraffins (SCCPs) has attracted great attention. However, the toxicity of SCCPs on male reproductive system remains ambiguous. In this study, we treated mice with SCCPs by gavage and investigated the toxic effects of SCCPs on testis. According to the results, the sperm parameters of mice were significantly reduced after exposure to 1, 10, 100 mg/kg body mass per day SCCPs for 35 days. SCCPs resulted in disorderly arranged seminiferous epithelium and increased apoptotic cells in testes. Both in vivo and in vitro experiments indicated that the oxidative stress was induced after SCCPs exposure, and dysfunction of nuclear factor erythroid-related factor (NRF2) signaling pathway played a role in this process. Moreover, resveratrol, an NRF2 activator, could alleviate the damage of SCCPs onmale reproductive system. Our study indicated that oxidative stress is the key point for explaining the testicular toxicity caused by SCCPs, and NRF2 could be used as a potential target for clinical treatment to alleviate the reproductive toxicity induced by SCCPs.


Assuntos
Hidrocarbonetos Clorados , Parafina , Animais , Masculino , Camundongos , China , Monitoramento Ambiental/métodos , Hidrocarbonetos Clorados/toxicidade , Fator 2 Relacionado a NF-E2/genética , Parafina/toxicidade , Parafina/análise , Sêmen/química , Testículo , Estresse Oxidativo
7.
J Ovarian Res ; 16(1): 87, 2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37120599

RESUMO

n-3 PUFAs are classic antioxidant that can be used to treat follicular dysplasia and hyperinsulinemia caused by excessive oxidative stress in PCOS women. To investigate the effect of n-3 PUFA supplementation on the oocyte quality of polycystic ovary syndrome (PCOS) mice during in vitro maturation, a PCOS mouse model was established by dehydroepiandrosterone (DHEA). The GV oocytes of the control and PCOS groups were collected and cultured in vitro with or without n-3 PUFAs. After 14 h, the oocytes were collected. Our data demonstrated that the oocyte maturation rate of PCOS mice significantly increased after the addition of 50 µM n-3 PUFAs. The results of immunofluorescence showed that the abnormal rates of spindles and chromosomes in the PCOS + n-3 PUFA group were lower than those in the PCOS group. The mRNA expression of an antioxidant-related gene (Sirt1) and DNA damage repair genes (Brca1/Msh2) was found to be significantly rescued after n-3 treatment. Additionally, the results of living cell staining showed that the addition of n-3 PUFAs could reduce the levels of reactive oxygen species and mitochondrial superoxide in PCOS oocytes. In conclusion, the addition of 50 µM n-3 PUFAs during the in vitro maturation of PCOS mouse oocytes can improve the maturation rate by reducing the level of oxidative stress and the rate of spindle/chromosome abnormalities, providing valuable support during the IVM process.


Assuntos
Ácidos Graxos Ômega-3 , Síndrome do Ovário Policístico , Humanos , Feminino , Animais , Camundongos , Técnicas de Maturação in Vitro de Oócitos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Oócitos/metabolismo , Suplementos Nutricionais
8.
J Ovarian Res ; 16(1): 138, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37443082

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. METHODS: We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. RESULTS: We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1ß, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. CONCLUSION: These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3 , Microbioma Gastrointestinal , Síndrome do Ovário Policístico , Animais , Feminino , Camundongos , Desidroepiandrosterona/toxicidade , Microbioma Gastrointestinal/fisiologia , Resistência à Insulina , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/fisiopatologia , Ácidos Graxos Ômega-3/uso terapêutico
9.
Cell Death Discov ; 9(1): 163, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37188682

RESUMO

In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36612683

RESUMO

Understanding land use change and its impact on habitat quality (HQ) is conducive to land use management and ecological protection. We used the InVEST model and the GeoDetector model to explore the land use and HQ of Wusu from 1980 to 2020. We found that the spatial distribution of land use in Wusu had the most dramatic change from 2000 to 2010, and accordingly, the habitat quality deteriorated seriously from 2000 to 2010. Via correlation analysis, the response of HQ to land use change is obvious, among which the negative effect of forest land to construction land is the largest, and the positive effect of construction land to water is the largest. However, the overall HQ had the largest negative response to the change of grassland to arable land, and the largest positive response to the change of unused land to grassland. Of the driving factors that cause land use change and thus affect HQ, the human factors are the strongest, and the negative impact on HQ is more irreversible. This study can provide a scientific basis for land use management and ecological protection in Wusu, and can help to further promote the exploration of human activities and ecological responses in arid and semi-arid areas.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Humanos , Florestas , China , Atividades Humanas
11.
IEEE Trans Cybern ; 49(7): 2591-2604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30028717

RESUMO

This paper is concerned with the stabilization problem of type-2 fuzzy systems with network-induced packet losses. By regarding the packet lost process as an unstable mode of a switched system, the stability of the system is then guaranteed with the aid of the mode-dependent average dwell time approach in the sense of the slow and fast switching. The discrete-time multiple discontinuous Lyapunov function is also utilized for the analysis. Two sufficient conditions regarding the stability and the stabilization of the system are proposed. The state-feedback matrices can be then calculated from the conditions to ensure the criterion that the packet-loss rate is no larger than a specific constant. Two practical examples are given to illustrate the feasibility and effectiveness of the proposed method.

12.
IEEE Trans Neural Netw Learn Syst ; 29(8): 3404-3417, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28792906

RESUMO

The model approximation problem is studied in this paper for switched genetic regulatory networks (GRNs) with time-varying delays. We focus on constructing a reduced-order model to approximate the high-order GRNs considered under the switching signal subject to certain constraints, such that the approximation error system between the original and reduced-order systems is exponentially stable with a disturbance attenuation performance. The stability conditions and the disturbance attenuation performance are established by utilizing two integral inequality bounding techniques and the average dwell-time method for the approximation error system. Then, the solvability conditions for the reduced-order models for the GRNs are also established using the projection method. Furthermore, the model approximation problem can be transferred into a sequential minimization problem that is subject to linear matrix inequality constraints by using the cone complementarity algorithm. Finally, several examples are provided to illustrate the effectiveness and the advantages of the proposed methods.


Assuntos
Simulação por Computador , Redes Reguladoras de Genes , Modelos Genéticos , Animais , Humanos , Fatores de Tempo
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1553-1558, 2018 Oct.
Artigo em Zh | MEDLINE | ID: mdl-30295283

RESUMO

OBJECTIVE: To study the coagulation properties the refrigerated whole blood stored at 4℃. METHODS: Ten units of whole blood were obtained from healthy volunteer donors and stored at 4±2℃ for 21 days. Samples were collected on the day after donation and on days 2, 4, 6, 8, 10, 14 and 21 for delection including complete blood count, electrolyte, APTT, PT, Fg, blood coagulation factors, and thromboelastography(TEG). RESULTS: The levels of Hb, WBC, Plt, sodium and potassium in each sample accorded with standard of storing whole blood. The level of Hb, WBC, Plt and Na+ decreased along with prolonging of storage time, while the K+ level increased along with prolonging of stored time, APTT and PT prolonged along with prolonging of thored time, PT>17 min at d 21, the Fg level change was no-obvious, The level of factor Ⅴ and Ⅷ decreased more than 50 % of baseline on d 6 and 4 respectively; the levels of factor Ⅱ, Ⅶ, Ⅸ, Ⅹ, Ⅺ, Ⅻ showed decreasing trend, but their levels were less than 40 % of baseline values at d 21. TEG test showed that no abnormalily of R value was found, the abnormal valnes of K and Angle were observed at d 21, the abnormal value of MA was observed at d 14. CONCLUSION: The whole blood stored for 10 days possesses normal coagulation function showing important significance for treatment of hemorrhage from war injury and surgical openation of heart and chest.


Assuntos
Coagulação Sanguínea , Tromboelastografia , Fatores de Coagulação Sanguínea , Testes de Coagulação Sanguínea , Hemorragia , Humanos
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