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1.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338822

RESUMO

The hippocampal formation, particularly the CA2 subregion, is critical for social memory formation and memory processing, relying on synaptic plasticity-a fundamental mechanism by which synapses strengthen. Given the role of the ubiquitin-proteasome system (UPS) in various nervous system processes, including learning and memory, we were particularly interested in exploring the involvement of RING-type ubiquitin E3 ligases, such as UHRF2 (NIRF), in social behavior and synaptic plasticity. Our results revealed altered social behavior in mice with systemic Uhrf2 knockout, including changes in nest building, tube dominance, and the three-chamber social novelty test. In Uhrf2 knockout mice, the entorhinal cortex-CA2 circuit showed significant reductions in synaptic plasticity during paired-pulse facilitation and long-term potentiation, while the inability to evoke synaptic plasticity in the Schaffer-collateral CA2 synapses remained unaffected. These changes in synaptic plasticity correlated with significant changes in gene expression including genes related to vesicle trafficking and transcriptional regulation. The effects of Uhrf2 knockout on synaptic plasticity and the observed gene expression changes highlight UHRF2 as a regulator of learning and memory processes at both the cellular and systemic levels. Targeting E3 ubiquitin ligases, such as UHRF2, may hold therapeutic potential for memory-related disorders, warranting further investigation.


Assuntos
Hipocampo , Plasticidade Neuronal , Ubiquitina-Proteína Ligases , Animais , Camundongos , Hipocampo/metabolismo , Transtornos da Memória/metabolismo , Camundongos Knockout , Plasticidade Neuronal/genética , Comportamento Social , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
2.
Food Res Int ; 165: 112431, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36869467

RESUMO

This study investigated the effect of dense phase carbon dioxide (DPCD) treatment on the organoleptic properties of new-paocai. Optimal DPCD treatment (25 MPa/40 °C/40 min) was determined by conducting single-factor and orthogonal experiments with the sensory, bactericidal, and electronic eye evaluations. DPCD treatment (25 MPa/40 °C/40 min) did not significantly affect the nitrite, pH, total acid, and organic acid of the new-paocai brine, and the texture of the radish slices did not display substantial changes. Gas chromatography-mass spectrometry (GC-MS) was employed to characterize the new-paocai brine flavor, revealing 63 and 60 respective flavor compounds with and without DPCD treatment. In addition, DPCD treatment significantly reduced the total organic volatile compound content in the paocai from 48.182 µg/mL to 35.952 µg/mL, DPCD has a great influence on volatile flavor substances. The electronic nose (E-nose) effectively distinguished the flavor differences in the new-paocai brine with and without DPCD treatment. This study combined new food processing technology with traditional food production, could provide a new idea for pickle production technology.


Assuntos
Antibacterianos , Dióxido de Carbono , Nariz Eletrônico , Alimentos
3.
Ecotoxicol Environ Saf ; 246: 114163, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36240522

RESUMO

BACKGROUND: Flurochloridone (FLC), a selective herbicide used on a global scale, has been reported to have male reproductive toxicity whose evidence is limited, but its mechanism remains unclear. The present study was conducted to systematically explore the male reproductive toxicity of FLC, including sperm quality, spermatogenesis, toxicity targets, and potential mechanisms. METHODS: Male C57BL/6 mice aged 6-7 weeks received gavage administration of FLC (365/730 mg/kg/day) for 28 consecutive days. Then, the tissue and sperm of mice were collected for analysis. We measured the gonadosomatic index and analyzed sperm concentration, motility, malformation rate, and mitochondrial membrane potential (MMP). Spermatocyte immunofluorescence staining was performed to analyze meiosis. We also performed pathological staining on the testis and epididymis tissue and TUNEL staining, immunohistochemical analysis, and ultrastructural observation on the testicular tissue. RESULTS: Results showed that FLC caused testicular weight reduction, dysfunction, and architectural damage in mice, but no significant adverse effect was found in the epididymis. The exposure interfered with spermatogonial proliferation and meiosis, affecting sperm concentration, motility, kinematic parameters, morphology, and MMP, decreasing sperm quality. Furthermore, mitochondrial damage and apoptosis of testicular Sertoli cells were observed in mice treated with FLC. CONCLUSION: We found that FLC has significant adverse effects on spermatogonial proliferation and meiosis. Meanwhile, apoptosis and mitochondrial damage may be the potential mechanism of Sertoli cell damage. Our study demonstrated that FLC could induce testicular Sertoli cell damage, leading to abnormal spermatogenesis, which decreased sperm quality. The data provided references for the toxicity risk and research methods of FLC application in the environment.


Assuntos
Infertilidade Masculina , Células de Sertoli , Humanos , Masculino , Camundongos , Animais , Testículo , Camundongos Endogâmicos C57BL , Sêmen , Espermatogênese , Infertilidade Masculina/patologia , Espermatozoides
4.
Can J Microbiol ; 68(12): 758-768, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36194899

RESUMO

Diarrhea-predominant irritable bowel syndrome (IBS-D) is common among the captive South China tigers in zoos. 16S rRNA gene sequencing was performed to demonstrate the compositions and structures of the gastrointestinal microbiota of this species with IBS-D. Their healthy (F1) and mushy (F2) feces were allocated into two groups. A total of 21 and 31 fecal bacterial communities of major phyla and genera were detected, respectively. The F1 and F2 groups had five common microbiotas at the phylum level (Firmicutes, Proteobacteria, Fusobacteria, Actinobacteria, and Bacteroidetes). Among the five phyla, the abundance of Bacteroidetes in the F2 group was significantly lower than that in the F1 group. The diversity level of fecal microbiota within the mild-diarrhea stool was also significantly lower than that of the healthy counterpart. Thirty-two metabolites were correlated to four genus-level bacteria (Bacteroides, Pseudoclavibacter, Streptococcus, and Ruminococcaceae-UCG-005). Due to its normal role in protein degradation and metabolism, we hypothesized that the lower abundance of Bacteroides within the F2 group could be associated with the IBS-D symptoms. Therefore, this work implied that ameliorating the daily diet with a supplement of probiotics, such as Bacteroides, could improve the gut health of this species.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Tigres , Animais , Síndrome do Intestino Irritável/microbiologia , Tigres/genética , Tigres/microbiologia , RNA Ribossômico 16S/genética , Fezes/microbiologia , Diarreia/veterinária , Bactérias/genética , Metabolômica , Bacteroidetes/genética , China
5.
Acta Obstet Gynecol Scand ; 101(8): 889-900, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35645037

RESUMO

INTRODUCTION: Cesarean scar defect (CSD) is a long-term outcome of cesarean section (CS) and associated with numerous gynecological and obstetric problems. Previous studies indicate that infection may be a risk factor for CSD. Adjunctive azithromycin was shown to reduce the risk of postoperative infection in patients undergoing non-elective primary cesarean delivery in labor or after the rupture of membranes compared with standard antibiotic prophylaxis. This study investigated the protective effect of adjunctive azithromycin in combination with single-dose cephalosporin against CSD in women undergoing non-elective cesarean delivery. MATERIAL AND METHODS: A randomized, double-blind, controlled clinical trial was conducted in a University hospital in Shanghai, China. A total of 242 women who underwent their first non-elective CS were randomly assigned to receive 1500 mg cefuroxime sodium plus 500 mg intravenous azithromycin (n = 121; experimental group) or 1500 mg cefuroxime sodium plus a placebo (n = 121; placebo group). The primary outcome was CSD prevalence, as determined by transvaginal ultrasound and saline infusion sonohysterography within 6 months of delivery. Secondary outcomes were changes in infectious indicators (eg hypersensitive C-reactive protein and procalcitonin), postoperative morbidity, and use of postoperative antibiotics. We also examined the operative procedure, pathogenic microorganism cultures, and fetal outcomes. Outcomes were compared between groups with the chi-squared test, Fisher's exact test, or Student's t test. RESULTS: Between May 2018 and May 2021, 121 women were randomized to each arm. Because the sonographic follow up was disrupted by the coronavirus disease 2019 pandemic and strict management policies, we merged the follow-up time points (6 weeks and 6 months) into a single time period (6 weeks to 6 months); 104 and 108 women in the experimental and placebo groups, respectively, completed the first sonographic follow up. CSD was diagnosed by sonography in 34/104 (32.7%) and 50/108 (46.3%) patients in the experimental and placebo groups, respectively (relative risk 0.71, 95% confidence interval 0.50-0.99; p = 0.043). Characteristics of CSD and short-term infection outcomes did not differ between groups. CONCLUSIONS: A single dose of intravenous 500 mg azithromycin adjunctive to single-dose cefuroxime prophylaxis significantly reduced the incidence of CSD in women undergoing non-elective CS.


Assuntos
Tratamento Farmacológico da COVID-19 , Complicações Infecciosas na Gravidez , Antibioticoprofilaxia/efeitos adversos , Azitromicina/uso terapêutico , Cefuroxima/uso terapêutico , Cesárea/efeitos adversos , Cesárea/métodos , China , Cicatriz/epidemiologia , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Sódio
6.
J Food Sci ; 87(7): 2980-2998, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35638346

RESUMO

This experiment aimed to investigate the effects of four drying methods, namely, hot air drying (HAD), microwave drying (MD), vacuum drying (VD), and microwave vacuum drying (MVD), on the quality of lemon slices. The relevant indicators, including total phenolic content, ascorbic acid content, browning, color, reducing sugar content, volatile component measurements, and principal component analysis of 0 and 30 days storage, were compared after exposure to the four drying methods. The shortest time of 64 min was used to treat the lemon slices via MVD at 1 KW. These samples displayed the least damage after drying and the highest rehydration ratio of 4.12. The contents of VC, reducing sugars, and total phenols of MVD samples were significantly higher than those in the HAD, VD, and MD groups, retaining 105.94 mg/100 g, 21.35 g/100 g, and 77.81 mg GAE/g, respectively, while their color difference values were also the smallest, with a browning degree of 3.55, significantly lower than those in the other treatment groups (p < 0.05), and the degree of browning of the samples in the HAD treatment group was the most serious; in terms of volatile flavor substances, the lemon slice samples in the MVD and HAD treatment groups were more diverse and of better quality. The order of product sensory evaluation was: MVD > VD > HAD > MD. The final scores after comprehensive analysis revealed the order of the four drying methods as MVD, HAD, VD, and MD. Therefore, MVD had a better effect on the sensory perception and nutritional properties of the lemon slices, providing a useful alternative to the conventional drying method. PRACTICAL APPLICATION: Lemon slices during drying are affected by various aspects, leading to changes in its color, aroma substances, and nutrient composition. The results of this work will not only provide a technical reference for the future production of high-quality dried lemon slices, but also have important implications for fresh-cut lemons in processing and storage. It also generates important implications for fresh-cut lemons in processing and storage.


Assuntos
Dessecação , Micro-Ondas , Ácido Ascórbico/análise , Dessecação/métodos , Fenóis/análise , Vácuo
7.
Dev Cell ; 57(7): 901-913.e4, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35413238

RESUMO

The switch from mitosis to meiosis ensures the successive formation of gametes. However, it remains unclear how meiotic initiation occurs within the context of chromatin. Recent studies have shown that zinc finger HIT-type containing 1 (Znhit1), a subunit of the SRCAP chromatin remodeling complex, plays essential roles in modulating the chromatin structure. Herein, we report that the germline-conditional deletion of Znhit1 in male mice specifically blocks meiotic initiation. We show that Znhit1 is required for meiotic prophase events, including synapsis, DNA double-strand break formation, and meiotic DNA replication. Mechanistically, Znhit1 controls the histone variant H2A.Z deposition, which facilitates the expression of meiotic genes, such as Meiosin, but not the expression of Stra8. Interestingly, Znhit1 deficiency disrupts the transcription bubbles of meiotic genes. Thus, our findings identify the essential role of Znhit1-dependent H2A.Z deposition in allowing activation of meiotic gene expression, thereby controlling the initiation of meiosis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte , Células Germinativas , Meiose , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cromatina , Expressão Gênica , Células Germinativas/metabolismo , Histonas/metabolismo , Masculino , Meiose/genética , Camundongos
8.
Front Cell Dev Biol ; 9: 666303, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631693

RESUMO

The WNT signaling pathway plays a crucial role in oviduct/fallopian development. However, the specific physiological processes regulated by the WNT pathway in the fallopian/oviduct function remain obscure. Benefiting from the Lgr4 knockout mouse model, we report the regulation of oviduct epithelial secretion by LGR4. Specifically, the loss of Lgr4 altered the mouse oviduct size and weight, severely reduced the number of oviductal epithelial cells, and ultimately impaired the epithelial secretion. These alterations were mediated by a failure of CTNNB1 protein accumulation in the oviductal epithelial cytoplasm, by the modulation of WNT pathways, and subsequently by a profound change of the gene expression profile of epithelial cells. In addition, selective activation of the WNT pathway triggered the expression of steroidogenic genes, like Cyp11a1 and 3ß-Hsd1, through the activation of the transcriptional factor NR5A2 in an oviduct primary cell culture system. As demonstrated, the LGR4 protein modulates a WNT-NR5A2 signaling cascade facilitating epithelial secretory cell maturation and steroidogenesis to safeguard oviduct development and function in mice.

9.
J Assist Reprod Genet ; 38(12): 3175-3193, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34664184

RESUMO

Oxidative stress is one of the major causes leading to male infertility including asthenozoospermia. Hydrogen sulfide (H2S) has been widely recognized to be a potent antioxidant whose role is partially implemented by protein S-sulfhydration. However, protein S-sulfhydration has not been reported in germ cells. Therefore, we investigated whether asthenozoospermia could be associated with sperm protein S-sulfhydration. S-sulfhydrated proteins in human sperm were enriched via biotin-switch assay and analyzed using LC-MS/MS spectrometry. Two hundred forty-four S-sulfhydrated proteins were identified. Importantly, we validated that sperm histones H3.1 and H3.3 were the S-sulfhydrated proteins. Their S-sulfhydrated amino acid residue was Cysteine111. Abundances of S-sulfhydrated H3 (sH3) and S-sulfhydrated H3.3 (sH3.3) were significantly down-regulated in asthenozoospermic sperm, compared with the fertile controls, and were significantly correlated with progressive motility. Retinoic acid (RA) up-regulated level of sH3.3 in primary round spermatids and the C18-4 cells (a mouse spermatogonial stem cell line). Overexpression of the mutant H3.3 (Cysteine111 was replaced with serine) affected expression of 759 genes and raised growth rate of C18-4 cells. For the first time, S-sulfhydration H3 and H3.3 were demonstrated in the present study. Our results highlight that aberrant S-sulfhydration of H3 is a new pathophysiological basis in male infertility.


Assuntos
Astenozoospermia/fisiopatologia , Cisteína/metabolismo , Histonas/metabolismo , Espermatozoides/metabolismo , Compostos de Sulfidrila/metabolismo , Sequência de Aminoácidos , Animais , Biotina/metabolismo , Regulação da Expressão Gênica , Humanos , Sulfeto de Hidrogênio/metabolismo , Infertilidade/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Processamento de Proteína Pós-Traducional , Espermatogênese , Sulfetos/metabolismo
10.
Life Sci ; 278: 119570, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33964295

RESUMO

AIMS: Increasing evidence has shown that hormone secretion is regulated by endocytosis. Eps15 homology domain-containing protein 3 (EHD3) is an endocytic-trafficking regulatory protein, but whether EHD3 is associated with testosterone secretion is not clear. This work aims to explore the role of EHD3 in testosterone synthesis. MAIN METHODS: Testosterone concentration was determined by ELISA. The effects of EHD3 on endocytosis were assessed by exosomes tracing assay and Immunofluorescence. Targeting relationship between EHD3 and NR5A1 was verified by chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assay in Leydig cells. For in vivo assessments, conditional NR5A1 knockout mouse model was established with CRISPR/Cas9 gene targeting technology. KEY FINDINGS: EHD3 overexpression significantly increased the concentration of testosterone. EHD3 knockdown markedly decreased testosterone synthesis by reducing endocytosis. The activity of the EHD3 promoter was positively regulated by NR5A1, which occupied the conserved sequence "AGGTCA" in the EHD3 promoter. Furthermore, mice with a Leydig cell-specific conditional NR5A1 knockout displayed the blunted levels of EHD3 and clathrin (a key factor for endocytosis), and serum testosterone concentration compared with NR5A1f/f mice. SIGNIFICANCE: This study suggests a potential molecular mechanism of testosterone synthesis to fully understand male reproductive health.


Assuntos
Proteínas de Transporte/metabolismo , Endocitose , Exossomos/metabolismo , Regulação da Expressão Gênica , Fator Esteroidogênico 1/metabolismo , Testosterona/metabolismo , Animais , Sistemas CRISPR-Cas , Proteínas de Transporte/genética , Imunoprecipitação da Cromatina , Feminino , Células Intersticiais do Testículo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , RNA Interferente Pequeno/metabolismo , Fator Esteroidogênico 1/genética , Testosterona/farmacologia
11.
RSC Adv ; 11(36): 22125-22130, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35480835

RESUMO

The potential threat that has originated from chemical warfare agents (CWAs) has promoted the development of advanced materials to enhance the protection of civilian and military personnel. Zr-based metal-organic frameworks (Zr-MOFs) have recently been demonstrated as excellent catalysts for decomposing CWAs, but challenges of integrating the microcrystalline powders of Zr-MOFs into monoliths still remain. Herein, we report hierarchically porous monolithic UiO-66-X xerogels for the destruction of CWAs. We found that the UiO-66-NH2 xerogel with a larger pore size and a higher surface area than the UiO-66-NH2 powder possessed better degradability of 2-chloroethyl ethyl sulfide (2-CEES), which is a sulfur mustard simulant. These UiO-66-X xerogels exhibit outstanding performance for decomposing CWAs. The half-lives of vesicant agent sulfur mustard (HD) and nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) are as short as 14.4 min and 1.5 min, respectively. This work is, to the best of our knowledge, the first report on macroscopic monolithic UiO-66-X xerogels for ultrafast decomposition of CWAs.

12.
Can J Microbiol ; 67(5): 372-380, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33242254

RESUMO

Lolium perenne L. and Sorghum sudanense (Piper) Stapf. are 2 common forages fed to blue sheep (Pseudois nayaur Hodgson, 1833) in captivity. However, the effect of these 2 forages on the gastrointestinal microbiota is largely unknown. We analyzed the diversity of the microbiota in the feces of captive blue sheep fed with L. perenne (group F1) and S. sudanense (group F2) by 16S rRNA sequencing. A total of 20 major phyla and 29 genera fecal bacterial communities were detected in the 2 groups. The F1 and F2 groups shared common microbiota at the phylum level, which mainly consisted of Firmicutes and Bacteroidetes. Ruminococcaceae_UCG-005, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-013, and Ruminococcaceae_UCG-010 were the top 4 dominant taxa at the genus level. The percentage of Ruminococcaceae_UCG-010 was significantly higher in the F2 group (∼2.75-fold) than in F1 group. The diversity and abundance of the microbial community in F2 was higher than that in F1. Although both of L. perenne and S. sudanense affect the metabolism of the gastrointestinal microbiota of blue sheep, the S. sudanense improves more aspects of metabolism and biogenesis. In summary, our results demonstrated that L. perenne and S. sudanense affect blue sheep gastrointestinal microbiota in different ways. But S. sudanense efficiently improved the gastrointestinal microbiota of blue sheep.


Assuntos
Ração Animal , Bactérias/classificação , Fezes/microbiologia , Microbioma Gastrointestinal , Ovinos/microbiologia , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , DNA Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Lolium , Filogenia , RNA Ribossômico 16S/genética , Ovinos/metabolismo , Sorghum
13.
Sci Rep ; 10(1): 17424, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060690

RESUMO

This study aimed to develop and validate a model for the preoperative prediction of the effectiveness of hysteroscopic resection of a uterine cesarean niche in patients with postmenstrual spotting. The predictive model was developed in a primary prospective cohort consisting of 208 patients with niche treated by hysteroscopic resection. Multivariable logistic regression analysis was performed to develop the predictive model, which incorporated preoperative menstrual characteristics and magnetic resonance imaging (MRI) findings. Surgical efficacy was defined as a decrease in postmenstrual spotting duration of at least 3 days at the 3-month follow-up compared with baseline. The predictive model was presented with a nomogram, and the performance was assessed with respect to its calibration, discrimination, and clinical use. Internal validation was performed using tenfold cross-validation. The predictive factors in the final model were as follows: preoperative menstrual duration, thickness of the residual myometrium (TRM), length, TRM/thickness of the adjacent myometrium ratio, angle γ, area, and presence of a lateral branch of the niche. The model showed good performance in predicting the effectiveness of hysteroscopic niche resection. Incorporating the preoperative duration of the menstrual period and MRI findings of the niche into an easy-to-use nomogram facilitates the individualized prediction of the effectiveness of a hysteroscopic niche resection by 26 Fr resectoscope, but multicenter prospective studies are needed to validate it.


Assuntos
Cesárea/efeitos adversos , Cicatriz/cirurgia , Histeroscopia/métodos , Metrorragia/cirurgia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Nomogramas , Complicações Pós-Operatórias , Estudos Prospectivos , Resultado do Tratamento
14.
Ecotoxicol Environ Saf ; 202: 110881, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32574863

RESUMO

Exposure to ambient PM2.5 may correlate with the decline of semen quality, and the underlying biological mechanism has not been fully understood. In the present study, mice were intratracheally instilled with diesel exhaust PM2.5 (DEP), and its effects on the spermatogenic process as well as the alterations of testicular gene expression profile were assessed. Our results showed that chronic exposure to DEP impaired the fertility of male mice without influencing their libido. Compared with Vehicle-exposed group, the sperm count and motility from DEP-exposed mice were significantly decreased. In addition, immunohistological staining of γH2AX and DMC1, biomarkers for meiotic double strand breaks (DSBs), demonstrated that chronic exposure to DEP comprised the repair of meiotic DSBs, thus disrupting the spermatogenesis. Deep RNA sequencing test showed altered expressions of testicular genes including the GnRH signaling pathway. In summary, our research demonstrated that chronic exposure to DEP may disrupt spermatogenesis through targeting the meiotic recombination, providing a new perspective for the research on the male reproductive system damage caused by air pollution.


Assuntos
Poluentes Atmosféricos/toxicidade , Espermatogênese/efeitos dos fármacos , Emissões de Veículos/toxicidade , Animais , Fertilidade , Masculino , Camundongos , Material Particulado/toxicidade , Análise do Sêmen , Espermatozoides/efeitos dos fármacos , Testículo
15.
Cell Death Dis ; 11(2): 142, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081844

RESUMO

5'-hydroxymethylcytosine (5hmC), an important 5'-cytosine modification, is altered highly in order in male meiotic prophase. However, the regulatory mechanism of this dynamic change and the function of 5hmC in meiosis remain largely unknown. Using a knockout mouse model, we showed that UHRF1 regulated male meiosis. UHRF1 deficiency led to failure of meiosis and male infertility. Mechanistically, the deficiency of UHRF1 altered significantly the meiotic gene profile of spermatocytes. Uhrf1 knockout induced an increase of the global 5hmC level. The enrichment of hyper-5hmC at transcriptional start sites (TSSs) was highly associated with gene downregulation. In addition, the elevated level of the TET1 enzyme might have contributed to the higher 5hmC level in the Uhrf1 knockout spermatocytes. Finally, we reported Uhrf1, a key gene in male meiosis, repressed hyper-5hmC by downregulating TET1. Furthermore, UHRF1 facilitated RNA polymerase II (RNA-pol2) loading to promote gene transcription. Thus our study demonstrated a potential regulatory mechanism of 5hmC dynamic change and its involvement in epigenetic regulation in male meiosis.


Assuntos
5-Metilcitosina/análogos & derivados , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Infertilidade Masculina/enzimologia , Prófase Meiótica I , Espermatócitos/enzimologia , Testículo/enzimologia , Ubiquitina-Proteína Ligases/metabolismo , 5-Metilcitosina/metabolismo , Animais , Proteínas Estimuladoras de Ligação a CCAAT/deficiência , Proteínas Estimuladoras de Ligação a CCAAT/genética , Linhagem Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo , Epigênese Genética , Fertilidade , Infertilidade Masculina/genética , Infertilidade Masculina/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , RNA Polimerase II/metabolismo , Transdução de Sinais , Espermatócitos/patologia , Espermatogênese , Testículo/patologia , Testículo/fisiopatologia , Ativação Transcricional , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/genética
16.
BMJ Open ; 10(1): e032379, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31915163

RESUMO

INTRODUCTION: Perioperative infections may be considered predictors of caesarean scar defect (CSD), and multidose antibiotics have a protective effect against CSD. However, the ability of adjunctive azithromycin combined with cephalosporin to reduce the prevalence of CSD remains unclear. The planned study aims to clarify the protective effect of antibiotics against CSD and to assess the effectiveness of adjunctive azithromycin prophylaxis for CSD. METHODS AND ANALYSIS: This study is a double-blind, parallel-control randomised clinical trial that will be carried out at the International Peace Maternity and Child Health Hospital. A total of 220 eligible patients will be randomised (1:1) to receive either adjunctive azithromycin or single-dose cephalosporin 30 min before the incision. The evaluation criteria are the prevalence and characteristics of CSD as assessed by transvaginal ultrasound (TVU) and saline infusion sonohysterography (SIS) at 42 days, 6 months and 12 months after delivery. The primary outcome will be the prevalence of CSD, and the characteristics of CSD will be assessed by TVU and SIS 42 days after delivery; all other outcomes are secondary. ETHICS AND DISSEMINATION: This protocol received authorisation from the Medical Research Ethics Committee of International Peace Maternity and Child Health Hospital on 25 April 2018 (approval no. GKLW2017-84). The findings will be reported in peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17013272.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Azitromicina/uso terapêutico , Cefalosporinas/uso terapêutico , Cesárea/efeitos adversos , Cicatriz/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Complicações Pós-Operatórias/prevenção & controle , Gravidez
17.
BMC Bioinformatics ; 20(Suppl 5): 179, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31272367

RESUMO

BACKGROUND: The Chinese National Infrastructure of Cell Line stores and distributes cell lines for biomedical research in China. This study aims to represent and integrate the information of NICR cell lines into the community-based Cell Line Ontology (CLO). RESULTS: We have aligned, represented, and added all identified 2704 cell line cells in NICR to CLO. We also proposed new ontology design patterns to represent the usage of cell line cells as disease models by inducing tumor formation in model organisms, and the relations between cell line cells and their expressed or overexpressed genes or proteins. The resulting CLO-NICR ontology also includes the Chinese representation of the NICR cell line information. CLO-NICR was merged into the general CLO. To serve the cell research community in China, the Chinese version of CLO-NICR was also generated and deposited in the OntoChina ontology repository. The usage of CLO-NICR was demonstrated by DL query and knowledge extraction. CONCLUSIONS: In summary, all identified cell lines from NICR are represented by the semantics framework of CLO and incorporated into CLO as a most recent update. We also generated a CLO-NICR and its Chinese view (CLO-NICR-Cv). The development of CLO-NICR and CLO-NIC-Cv allows the integration of the cell lines from NICR into the community-based CLO ontology and provides an integrative platform to support different applications of CLO in China.


Assuntos
Ontologias Biológicas , Interface Usuário-Computador , Pesquisa Biomédica , Linhagem Celular , China , Bases de Dados Factuais , Humanos
19.
J Minim Invasive Gynecol ; 26(4): 671-678, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30031208

RESUMO

STUDY OBJECTIVE: To investigate whether there are left-right asymmetries, factors affecting lateral dominance, and clinical feature differences in the left and right sides of tubal pregnancy (TP). DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University. PATIENTS: Patients (n = 6186) with TP treated surgically. INTERVENTIONS: We used data from the digital medical records system of the hospital. Women diagnosed with ectopic pregnancy(EP) between January 2005 and December 2016 in the inpatient department of gynecology were included. All data from the medical files were obtained retrospectively, including demographic characteristics; reproductive, gynecologic, and surgical history; clinical features; and treatment. Patients who were previously treated by salpingectomy or nonsurgical management and those with unknown-site EP or non-TPs were excluded. MEASUREMENTS AND MAIN RESULTS: The overall frequency of right-sided TP was 54.48% (3370/6186), which is significantly higher than 50% (p < .001, binominal test). The proportion of right-sided TPs decreased with age (p for trend = .007) and from the proximal (interstitial) end to the distal (fimbrial) end of the tube (p for trend = .017). Of the TP patients with a corpus luteum, we found the corpus luteum was more frequently located in the right ovary (p < .001) and in the contralateral ovary to the TP side in 41.38% of cases. However, tubal rupture was more frequent in left TP than the in right TP (p = .005). CONCLUSION: The left-right asymmetries of TP include right-side dominance and the clinical feature differences between the 2sides of TP.


Assuntos
Gravidez Tubária/epidemiologia , Adolescente , Adulto , China/epidemiologia , Tubas Uterinas , Feminino , Fertilidade , Hospitais , Humanos , Pessoa de Meia-Idade , Cistos Ovarianos/epidemiologia , Gravidez , História Reprodutiva , Estudos Retrospectivos , Adulto Jovem
20.
Acta Obstet Gynecol Scand ; 98(4): 413-422, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30444954

RESUMO

INTRODUCTION: The aim of this study was to explore the prevalence and predictors of cesarean scar defect (CSD) at 6 weeks postpartum in Shanghai, China. MATERIAL AND METHODS: Women scheduled to receive a cesarean section (CS) were recruited from a university hospital. Surgery-related factors, pregnancy complications, routine examinations, perioperative medications, and physical signs were collected and transvaginal ultrasonography was performed to assess the presence of a CSD at 6 weeks postpartum. Multivariate logistic regression was applied to identify the predictors for CSD. RESULTS: A CSD was detected in 223 of 514 women (43.4%, 95% CI 39.1%-47.7%) by transvaginal ultrasonography. Of women with normal temperature (T < 37.5°C, CSD prevalence 33.9%, 95% CI 28.4%-39.5%), women with postpartum fever (T ≥ 38°C, CSD 44.1%, 95% CI 31.0%-57.1%), and women who were subfebrile in the postpartum (37.5 ≤ T ≤ 38.0°C, CSD 58.3%, 95% CI 50.9%-65.7%), the latter two had significantly increased risk for CSD (adjusted odds ratio [aOR] 2.7, 95% CI 1.3-5.2 and aOR 3.3, 95% CI 2.1-5.3, respectively). In comparison to single-dose antibiotic administration (CSD 49.0%, 95% CI 43.8%-54.3%), multi-dose antibiotic administration (CSD 31.1%, 95% CI 23.8%-38.3%) had a protective effect (aOR 0.4, 95% CI 0.3-0.7). Postpartum fever, intrapartum infection, emergency CS, and cervical dilation ≥ 3 cm were found to be the main predictors of multi-dose antibiotics management. Low platelet count postpartum (defined as ≤ 150 × 109 /L) and high fibrinogen pre-CS (defined as ≥ 4.5 g/L) increased CSD risk (aOR 2.0, 95% CI 1.1-3.6 and 1.7, 95% CI 1.1-2.5, respectively). CONCLUSIONS: The prevalence of CSD in the Chinese population is high enough to be a concern. Perioperative infection and hypercoagulability should be considered CSD predictors, and multi-dose antibiotics have a protective effect.


Assuntos
Cesárea/efeitos adversos , Cicatriz/diagnóstico por imagem , Cicatriz/etiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Adulto , Cesárea/estatística & dados numéricos , China/epidemiologia , Cicatriz/epidemiologia , Feminino , Humanos , Complicações Pós-Operatórias/epidemiologia , Período Pós-Parto , Prevalência , Fatores de Risco , Adulto Jovem
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