RESUMO
The separation of enantiomers using high-performance chromatography technologies represents great importance and interest. In this aspect, ß-cyclodextrin (ß-CD) and its derivatives have been extensively studied as chiral stationary phases (CSPs). Nevertheless, ß-CD that was immobilized on a traditional matrix often exhibited low stabilities and limited operating ranges. Recently, covalent organic frameworks (COFs) with highly ordered nanopores are emerging as promising CSPs for enantioseparations, but their practical applications are still hampered by the difficulty of monomer and COF synthesis. Herein, two ß-CD-driven COFs are synthesized via a fast and facile plasma-induced polymerization combined postsynthesis modification strategy. The precisely defined COF channels enhanced the accessibility of the accommodated ß-CD to the analytes and acted as robust protective barriers to safeguard the ß-CD from harsh environments. Therefore, the ß-CD-modified COFs can be potentially general CSPs for extensive enantioseparation in both gas chromatography and high-performance liquid chromatography, and a wide range of racemates were separated. Compared to the commonly employed commercial chiral columns, these COF-based columns exhibited comparable resolution capability and superior application versatility. This work integrates the advantages and overcomes the defects of COFs and ß-CD, thus advancing COFs as platforms for chiral selector modification and giving great promise for practical chromatographic enantioseparation.
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Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also known as Müllerian agenesis, is characterized by uterovaginal aplasia in an otherwise phenotypically normal female with a normal 46,XX karyotype. Previous studies have associated sequence variants of PAX8, TBX6, GEN1, WNT4, WNT9B, BMP4, BMP7, HOXA10, EMX2, LHX1, GREB1L, LAMC1, and other genes with MRKH syndrome. The purpose of this study was to identify the novel genetic causes of MRKH syndrome. Ten patients with MRKH syndrome were recruited at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Whole-exome sequencing was performed for each patient. Sanger sequencing confirmed the potential causative genetic variants in each patient. In silico analysis and American College of Medical Genetics and Genomics (ACMG) guidelines helped to classify the pathogenicity of each variant. The Robetta online protein structure prediction tool determined whether the variants affected protein structures. Eleven variants were identified in 90% (9/10) of the patients and were considered a molecular genetic diagnosis of MRKH syndrome. These 11 variants were related to nine genes: TBC1D1, KMT2D, HOXD3, DLG5, GLI3, HIRA, GATA3, LIFR, and CLIP1. Sequence variants of TBC1D1 were found in two unrelated patients. All variants were heterozygous. These changes included one frameshift variant, one stop-codon variant, and nine missense variants. All identified variants were absent or rare in gnomAD East Asian populations. Two of the 11 variants (18.2%) were classified as pathogenic according to the ACMG guidelines, and the remaining nine (81.8%) were classified as variants of uncertain significance. Robetta online protein structure prediction analysis suggested that missense variants in TBC1D1 (p.E357Q), HOXD3 (p.P192R), and GLI3 (p.L299V) proteins caused significant structural changes compared to those in wild-type proteins, which in turn may lead to changes in protein function. This study identified many novel genes, especially TBC1D1, related to the pathogenesis of MRKH syndrome. The identification of these variants provides new insights into the etiology of MRKH syndrome and a new molecular genetic reference for the development of the reproductive tract.
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Transtornos 46, XX do Desenvolvimento Sexual , Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico , Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas , Feminino , Genômica , Humanos , Ductos Paramesonéfricos/anormalidades , Sequenciamento do ExomaRESUMO
Homeobox transcript antisense RNA (HOTAIR) is a long non-coding RNA associated with a number of fibrosis-related diseases. The aim of this study was to investigate the specific role of HOTAIR in the development of endometrial fibrosis and to identify the molecular mechanisms underlying this process. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of HOTAIR in samples of intrauterine adhesion (IUA) tissue and in endometrial stromal cells (ESCs) that had been treated with transforming growth factor beta 1 (TGF-ß1). Additionally, we transfected ESCs with either overexpression plasmid (pcDNA-HOTAIR) or silencing construct (si-HOTAIR) and then treated these cells with TGF-ß1. We then performed RT-qPCR and western blot analysis, along with cell proliferation and apoptosis assays, to investigate the effects of HOTAIR on the transdifferentiation of ESCs into myofibroblasts. The results showed that the expression levels of HOTAIR were significantly elevated in IUA tissue and in ESCs that had been treated with TGF-ß1. The overexpression of HOTAIR had a pro-fibrotic effect on ESCs, while the silencing of HOTAIR exerted an anti-fibrotic effect. Most importantly, the protein expression levels of p-Smad2 and p-Smad3 were significantly upregulated in TGF-ß1-treated ESCs transfected with pcDNA-HOTAIR and were downregulated after transfection with si-HOTAIR constructs. These data indicate that HOTAIR promotes endometrial fibrosis by activating the TGF-ß1/Smad signaling pathway, suggesting that the inhibition of HOTAIR may represent a promising therapeutic option for suppressing endometrial fibrosis.
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Fibrose/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Doenças Uterinas/genética , Actinas/metabolismo , Adulto , Apoptose/genética , Proliferação de Células/genética , Transdiferenciação Celular/genética , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Feminino , Técnicas de Silenciamento de Genes , Humanos , Cultura Primária de Células , Transdução de Sinais/genética , Proteína Smad2/genética , Proteína Smad3/genética , Células Estromais/metabolismo , Aderências Teciduais/genética , Aderências Teciduais/metabolismo , Fator de Crescimento Transformador beta1/fisiologia , Regulação para Cima , Doenças Uterinas/patologiaRESUMO
Porous organic cages (POCs) have attracted extensive attention due to their unique structures and tremendous application potential in numerous areas. In this study, an enantioselective potentiometric sensor composed of a polyvinyl chloride (PVC) membrane electrode modified with CC3-R POC material was used for the recognition of enantiomers of 2-amino-1-butanol. After optimisation, the developed sensor exhibited enantioselectivity toward S-2-amino-1-butanol ( log K S , R P o t = -0.98) with acceptable sensitivity, and a near-Nernstian response of 25.8 ± 0.3 mV/decade within a pH range of 6.0â»9.0.
Assuntos
Amino Álcoois/química , Técnicas Eletroquímicas , Eletrodos , Concentração de Íons de Hidrogênio , Membranas Artificiais , Estrutura Molecular , Cloreto de Polivinila/química , Porosidade , Potenciometria , Sensibilidade e Especificidade , EstereoisomerismoRESUMO
A new enantioselective potentiometric sensor containing R-type chiral porous organic cage CC9 as the chiral selector was designed for the assay of 2-aminobutanol. Optimized membrane electrodes displayed a linear dynamic range from 10-3 ~ 10-1 mol·L-1 with a detection limit of 2.5 × 10-4 mol·L-1 and a Nernstian response of 27 ± 0.5mV·decade-1 toward S-2-aminobutanol within the pH range 7.0-10.0. The potentiometric enantioselectivity coefficient ( logKS,RPot) of this sensor was -1.333, indicating that the porous organic cage-based electrode exhibited good discrimination toward S-2-aminobutanol over R-2-aminobutanol.
Assuntos
Amino Álcoois/análise , Amino Álcoois/química , Técnicas de Química Analítica/instrumentação , Eletrodos , Utensílios Domésticos , Concentração de Íons de Hidrogênio , Limite de Detecção , Modelos Moleculares , Conformação Molecular , Porosidade , Potenciometria , EstereoisomerismoRESUMO
Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl-ß-cyclodextrin were prepared for chiral dialysis separations. After optimizing the membrane material concentrations, the membrane preparation conditions and the feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were obtained for mandelic acid on the cellulose membrane, p-hydroxy phenylglycine on the sodium alginate membrane, and p-hydroxy phenylglycine on the hydroxypropyl-ß-cyclodextrin membrane, respectively. To study the optical resolution mechanism, chiral discrimination by membrane adsorption, solid phase extraction, membrane chromatography, high-pressure liquid chromatography ultrafiltration were performed. All of the experimental results showed that the first adsorbed enantiomer was not the enantiomer that first permeated the membrane. The crystal structures of mandelic acid and p-hydroxy phenylglycine are the racematic compounds. We suggest that the chiral separation mechanism of the solid membrane is "adsorption - association - diffusion," which is able to explain the optical resolution of the enantioselective membrane. This is also the first report in which solid membranes of sodium alginate and hydroxypropyl-ß-cyclodextrin were used in the chiral separation of p-hydroxy phenylglycine.
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2-Hidroxipropil-beta-Ciclodextrina/química , Alginatos/química , Celulose/química , Membranas Artificiais , Fenômenos Ópticos , Cromatografia Líquida de Alta Pressão , Ácido Glucurônico/química , Glicina/análogos & derivados , Glicina/química , Glicina/isolamento & purificação , Ácidos Hexurônicos/química , EstereoisomerismoRESUMO
Metal-organic frameworks are promising porous materials. Chiral metal-organic frameworks have attracted considerable attention in controlling enantioselectivity. In this study, a homochiral metal-organic framework [Co(2) (D-cam)(2) (TMDPy)] (D-cam = D-camphorates, TMDPy = 4,4'-trimethylenedipyridine) with a non-interpenetrating primitive cubic net has been used as a chiral stationary phase in high-performance liquid chromatography. It has allowed the successful separation of six positional isomers and six chiral compounds. The good selectivity and baseline separation, or at least 60% valley separation, confirmed its excellent molecular recognition characteristics. The relative standard deviations for the retention time of run-to-run and column-to-column were less than 1.8 and 3.1%, respectively. These results demonstrate that [Co(2) (D-cam)(2) (TMDPy)] may represent a promising chiral stationary phase for use in high-performance liquid chromatography.
Assuntos
Cromatografia Líquida de Alta Pressão/instrumentação , Metais/química , Compostos Orgânicos/química , Cromatografia Líquida de Alta Pressão/métodos , EstereoisomerismoRESUMO
BACKGROUND: Müllerian duct anomalies (MDAs) are congenital developmental disorders exhibiting as a variety of malformations of female reproductive tract. The identified etiology of MDAs is limited. The present study aimed to unravel the underlying genetic causes of MDAs. METHODS: Rare variants in androgen receptor (AR) were called from the cohort consists of patients with MDAs and underwent whole exome sequencing (WES) at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Sanger sequencing was used to confirm the causative genetic mutations. In silico analysis were used to classify the pathogenicity of each variant. Molecular modeling and simulations were conducted to investigate the conformational changes between the wild-type (WT) and mutant proteins. RESULTS: A total of 3 rare heterozygous variants in AR from the MDAs cohort in our institution were identified, with unknown effects. All variants were missense mutations, including c.173A > T, c.558C > A and c.1208C > T, and were absent or rare in East Asian populations in Genome Aggregation Database and the Exome Aggregation Consortium Database. According to the American College of Medical Genetics and Genomics guidelines, c.1208C > T variant was classified as likely pathogenic, while the other two were variants of uncertain significance. During molecular dynamics simulations, WT and mutant proteins all reached stable status according to root-mean-square variance. Values of radius of gyration showed that Q58L and S186R protein would be more compact than WT, while the structure of A403V became looser. Despite, in comparison with WT, the number of hydrogen bonds increased in Q58L, while decreased in the other two variants. Furthermore, the solvent-accessible surface area diminished in Q58L and A403V while enlarged in S186R proteins, when compared with WT. CONCLUSIONS: To our knowledge, this is the first report regarding the association of AR mutation and MDAs. The identification of these variants, predicted to damage the structure and function of AR protein, not only expanded the mutational spectrum of causative genes of MDAs, but provide novel molecular genetic reference for future studies.
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Ductos Paramesonéfricos , Receptores Androgênicos , Gravidez , Humanos , Feminino , Ductos Paramesonéfricos/anormalidades , Receptores Androgênicos/genética , Mutação , Mutação de Sentido Incorreto , Proteínas MutantesRESUMO
Covalent organic frameworks ï¼COFsï¼ are an emerging class of porous crystalline materials composed of multidentate organic units connected by covalent bonds. COFs have been demonstrated to exhibit great potential and research value in many fieldsï¼ including gas storage and separationï¼ photoelectric devicesï¼ fluorescence sensorsï¼ catalysisï¼ drug deliveryï¼ dye and pollutant adsorptionï¼ and electronic devicesï¼ and so on. The COFs obtained by post-synthesis modification tend to exhibit high crystallinities and porositiesï¼ thereby rendering them suitable materials for use in the fields of chiral resolutionï¼ asymmetric catalysisï¼ and chromatography. In this workï¼ TpPa-NO2 was synthesized from 1ï¼3ï¼5-tricarbaldehyde phloroglucinol and 2-nitro-1ï¼4-phenylenediamineï¼ which was then reduced to TpPa-NH2. Subsequentlyï¼ this material was modified with D-glucose via a post-synthesis modification strategy to obtain the TpPa-NH2-Glu. TpPa-NH2-Glu were characterized by nuclear magnetic resonance ï¼NMRï¼ spectroscopyï¼ Fourier transform-infrared ï¼FT-IRï¼ spectroscopyï¼ X-ray powder diffraction ï¼XRDï¼ analysisï¼ etc. In the XRD patternï¼ the peaks observed at 4.7°ï¼ 8.1°ï¼ 11.1°ï¼ and 27° were attributed to the TpPa-NH2-Gluï¼ and these peaks are consistent with previous reportsï¼ thereby confirming the successful synthesis of this derivative. In additionï¼ circular dichroism experiments indicated that the TpPa-NH2-Glu exhibited a Cotton effectï¼ further confirming the chiral COF was prepared. Subsequentlyï¼ this material was immobilized on the surface of spherical silica gel particles via the net-wrapping method to prepare a stationary phase for high performance liquid chromatographic column. Using n-hexane-isopropanol ï¼9â¶1ï¼ v/vï¼ or methanol-water ï¼9â¶1ï¼ v/vï¼ as mobile phases at a flow rate of 0.5 mL/minï¼ 16 racemates and two benzene-based positional isomers ï¼oï¼mï¼p-nitroaniline and oï¼mï¼p-Iodoanilineï¼ were successfully resolved by this chiral column. In additionï¼ under methanol-water ï¼9â¶1ï¼ v/vï¼ mobile phase conditionsï¼ five racemates were separatedï¼ among which propranolol hydrochlorideï¼ warfarinï¼ and metoprolol reached baseline separation. Furthermoreï¼ under n-hexane-isopropanol ï¼9â¶1ï¼ v/vï¼ mobile phase conditionsï¼ 11 racemates were resolvedï¼ among which ethyl 2-bromopropionate and 3-butyn-2-ol reached baseline separation. Meanwhileï¼ the effect of temperature on the TpPa-NH2-Glu liquid chromatography column and the repeatability of the TpPa-NH2-Glu liquid chromatography column were also explored. The HPLC column prepared by TpPa-NH2-Glu had good repeatabilityï¼ and its relative standard deviation ï¼RSDï¼ was 1.55% and 1.46%ï¼ respectively. It is demonstrated that the TpPa-NH2-Glu material has good resolution ability for chiral compounds.
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In order to investigate whether the use of single-walled carbon nanotubes can improve enantioseparations on an ionic liquid stationary phase, a chiral ionic liquid, (R)-N,N,N-trimethyl-2-aminobutanol-bis(trifluoromethanesulfon)imidate, was synthesized. Two capillary columns, one containing the chiral ionic liquid and the other containing the single-walled carbon nanotubes and the chiral ionic liquid, were then prepared for GC. The results of the separations achieved with these columns show that coating the chiral ionic liquid stationary phase onto the capillary column containing single-walled carbon nanotubes improves the enantioselectivety of the chiral ionic liquid. This work indicates that using single-walled carbon nanotubes in this manner enables the application range of such GC chiral separations to be extended.
Assuntos
Cromatografia Gasosa/instrumentação , Líquidos Iônicos/química , Nanotubos de Carbono/química , EstereoisomerismoRESUMO
Inorganic mesoporous silica gel spheres, which possess sufficient mechanical strength, thermal stability, and mobile phase endurance, are the most important and widely used materials for column packing in high performance liquid chromatography (HPLC). However, amorphous silica gel is generally reported as an inorganic chiral silica gel, and spherical all-inorganic chiral silica gel has not been reportedly used as the chiral stationary phase for HPLC. In this paper, inorganic spherical mesoporous silica gel was used in the method of polymerization-induced colloid aggregation (PICA), with silica sol as the raw material and L-glutamic acid (L-Glu) as the chiral monomer, to obtain mixed spheres of urea-formaldehyde resin and colloidal silica in a chiral environment. After high-temperature calcination (at 550 â) to remove the resin, inorganic mesoporous silica gel spheres based on L-Glu were prepared. Elemental analysis revealed that the prepared L-Glu chiral silica gel spheres were calcined completely, indicating that there were no organic constituents. Scanning electron microscopy (SEM) images of the silica gel spheres showed that the surface of the silica gel spheres was not smooth, with a uniform particle size of 3.0-4.5 µm. Transmission electron microscopy (TEM) images showed that the pore size distribution of the synthetic silica gel spheres was uniform due to the accumulation of pores. Nitrogen adsorption tests revealed that the specific surface area of L-Glu chiral silica gel spheres was 117.844 m2/g, the pore volume was 0.411 cm3/g, and the average pore size was 12.312 nm. All the characterizations indicated that the inorganic chiral mesoporous silicon had a regular spherical shape. The silica gel spheres possess frameworks and pore structures, providing a chiral microenvironment that is suitable as a chiral stationary phase for separating racemic compounds by HPLC. Because of the chiral pore structure and frameworks, the enantiomers were retained to different degrees and separation was achieved. The porous structure also increased the contact surface between the racemates and the active sites of the inner wall and improved the separation efficiency. Hydrogen bonding between the chiral stationary phase and the racemates, dipole interactions, and van der Waals forces were also involved in enantiomer resolution. An HPLC column was prepared with L-Glu chiral silica gel as the stationary phase and n-hexane-isopropanol (9â¶1, v/v) as the mobile phase. Fifteen racemic compounds were successfully separated on the chiral HPLC column, including seven racemic compounds for baseline separation, at a flow rate of 0.1 mL/min using 254 nm as the detection wavelength at 25 â. The separation of 10 benzene position isomers was successfully achieved, and eight of the benzene position isomers reached baseline separation. Experimental results showed that the chiral silica gel spheres possess sufficient mechanical strength and thermal stability, along with good chiral recognition ability and the ability to separate positional isomers. Compared with ordinary silica gel, these chiral silica gel spheres afforded better chiral separation and better separation of benzene position isomers, without further modification. The preparation of this chiral stationary phase also has the advantages of being cheap, convenient, and feasible.
Assuntos
Ácido Glutâmico/química , Sílica Gel , Dióxido de Silício , Cromatografia Líquida de Alta Pressão , Porosidade , EstereoisomerismoRESUMO
A strategy was designed for the molecular imprinting of magnetic nanoparticles with boric acid affinity (MNPs@MIP) which were then used for the selective recognition and isolation of glycoproteins. Fe3O4 nanoparticles were prepared by a solvothermal method and direct silanization by the condensation polymerization of aminopropyltriethoxysilane (APTES). Subsequently, phenylboric acid was functionalized by reductive amination between 2,3-difluoro-4-formyl phenylboric acid (DFFPBA) and the amido group. The resultant Fe3O4@SiO2-DFFPBA was then used for the selective adsorption of a glycoprotein template. Finally, a molecularly imprinted layer was covered on the surface nanoparticles by the condensation polymerization of tetraethyl orthosilicate (TEOS). The adsorption capacities of the resultant MNPs@MIP-HRP and MNPs@MIP-OVA to horseradish peroxidase (HRP) or ovalbumin (OVA) were significantly higher than non-imprinted particles (MNPs@NIP). Moreover, the adsorption capacities of MNPs@MIP-HRP and MNPs@MIP-OVA on non-template protein and non-glycoprotein bovine serum albumin (BSA) were significantly lower than those of their respective template proteins, thus indicating that both of the prepared MNPs@MIP exhibited excellent selectivity.
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OBJECTIVE: To explore the genetic causes of Herlyn-Werner-Wunderlich syndrome (HWWS) using whole-exome sequencing. DESIGN: Retrospective genetic study. SETTING: Academic medical center. PATIENT(S): Twelve patients with HWWS. INTERVENTION(S): Whole-exome sequencing was performed for each patient. Sanger sequencing was used to confirm the potential causative genetic variants. In silico analysis and American College of Medical Genetics and Genomics guidelines were used to classify the pathogenicity of each variant. MAIN OUTCOME MEASURE(S): Rare sequence variants associated with müllerian duct development and renal agenesis were identified and included in subsequent analyses. RESULT(S): A total of 11 variants were identified in 10 of 12 patients (83.3%) and were considered to constitute a molecular genetic diagnosis of HWWS. These 11 variants were related to 9 genes: CHD1L, TRIM32, TGFBR3, WNT4, RET, FRAS1, FAT1, FOXF1, and PCSK5. All variants were heterozygous and confirmed by Sanger sequencing. The changes included one frameshift variant, one splice-site variant, and eight missense variants. All of the identified variants were absent or rare in Genome Aggregation Database East Asian populations. One of the 11 variants (9.1%) was classified as a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines, and 8 of the 11 variants (72.7%) were classified as variants of uncertain significance. CONCLUSION(S): To our knowledge, this is the first report of the genetic causes of HWWS. Renal agenesis-related genes, such as CHD1L, TRIM32, RET, and WNT4, may be associated with HWWS. Identification of these variants can not only help us understand the etiology of HWWS and the relationship between reproductive tract development and urinary system development, but additionally improve the level of genetic counseling for HWWS.
Assuntos
Anormalidades Múltiplas , Anormalidades Congênitas/genética , Variação Genética , Nefropatias/congênito , Rim/anormalidades , Anormalidades Urogenitais/genética , Adolescente , Adulto , Criança , Anormalidades Congênitas/diagnóstico , Feminino , Predisposição Genética para Doença , Heterozigoto , Humanos , Nefropatias/diagnóstico , Nefropatias/genética , Fenótipo , Estudos Retrospectivos , Fatores de Risco , Síndrome , Anormalidades Urogenitais/diagnóstico , Sequenciamento do Exoma , Adulto JovemRESUMO
Endometriosis (Ems) is a common gynecological disease with the characteristics of infertility, pelvic pain, and sexual intercourse difficulty. Our present study aimed to investigate the effect of miR-199a-5p on cell mobility and epithelial-mesenchymal transition (EMT) in Ems. Ectopic endometrial stromal cells (EcSCs) and control endometrial stromal cells (CSCs) were isolated in our in vitro experiments. The level of miR-199a-5p in EcSCs was found much lower than that in CSCs. Besides, miR-199a-5p mimic suppressed the invasion and migration ability of EcSCs. At the same time, EMT was also found to be suppressed by miR-199a-5p mimic in EcSCs. Our further bioinformatics analysis and luciferase reporter assay revealed that ZEB1, a marker of EMT, was a direct target of miR-199a-5p. In addition, the combination of pcDNA3.1-ZEB1 weakened the inhibiting effect of miR-199a-5p mimic on the mobility and EMT of EcSCs. What is more, the PI3K/Akt/mTOR signal pathway was demonstrated to be inactivated by miR-199a-5p mimic. And then, the inducer of PI3K/Akt/mTOR signal pathway, IGF-1, abolished the effect of miR-199a-5p mimic on Ems progression. At last, an Ems rat model was established, and we found that miR-199a-5p agomir effectively suppressed the expression of vascular endothelial growth factor (VEGF) and EMT in vivo. The PI3K/Akt/mTOR signal pathway was also inactivated by miR-199a-5p agomir in our Ems rat model. Taken together, we concluded that miR-199a-5p targeted ZEB1 to inhibit the EMT of ovarian ectopic endometrial stromal cells via PI3K/Akt/mTOR signal pathway in vitro and in vivo, advancing our understanding of miR-199a-5p as regulators of Ems progression and making contribution to the treatment of Ems.
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Endometriose/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , MicroRNAs/metabolismo , Transdução de Sinais/fisiologia , Células Estromais/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Adulto , Animais , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Following the publication of this paper, the authors have realized that the authors' address affiliation was not presented as it should have officially appeared. The address affiliation should have appeared as "Department of Gynecology" (not "Gynecology Department"), Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing. Therefore, the authors' affiliation address should have been written as follows: Lifang Zhang, Ping Zheng, Aihong Duan, Yan Hao, Chang Lu and Dan Lu. Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, P.R. China. The authors confirm that there are no further errors in the study, and all the authors agree to this correction. The authors regret this error in the affiliation, and apologize for any inconvenience caused. [the original article was published in the Molecular Medicine Reports 19: 391399, 2019; DOI: 10.3892/mmr.2018.9656].
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Pelvic organ prolapse (POP) is an increasingly serious health problem that impairs quality of life and is caused by multiple additive genetic and environmental factors. As the uterosacral ligaments (ULs) provide primary support for the pelvic organs, it was hypothesized that disruption of these ligaments (as a result of aberrant methylation) may lead to a loss of support and eventually contribute to POP. In the present study, whether there are any aberrant methylations in the ULs of patients with POP compared to those of controls was investigated. Genomic DNA was isolated from the ULs of five women with POP and four women without POP, as controls, undergoing hysterectomy for benign conditions. An Illumina Infinium Methylation EPICBeadChips Infinium Human Methylation 850 K bead array was used to investigate the total methylation in the ULs. There were 3,723 differentially methylated CpG sites (Δß<0.14; P<0.05), including 3,576 hypermethylation and 147 hypomethylation sites in the ULs of patients with POP compared with the normal controls. There were more hypermethylated CpG sites, but a high ratio of hypomethylation between CpG islands and the Nshelf; in the gene structure, there was more hypermethylation than hypomethylation in TSS1500 and the 5' untranslated region. Gene ontology analysis demonstrated that these differentially methylated genes were associated with 'cell morphogenesis', 'extracellular matrix', 'cell junction', 'protein binding' and 'guanosine triphosphatase activity'. Several significant pathways were identified, including 'focal adhesion' and 'extracellular matrixreceptor interaction pathway'. This study provides evidence that there are differences in genomewide DNA methylation between ULs in menopausal women with and without POP, and that epigenetic mechanisms may partly contribute to POP pathogenesis.
Assuntos
Metilação de DNA , Genoma Humano , Ligamentos/metabolismo , Prolapso de Órgão Pélvico/genética , Sacro/metabolismo , Útero/metabolismo , Idoso , Estudos de Casos e Controles , Feminino , Redes Reguladoras de Genes , Humanos , Histerectomia , Ligamentos/patologia , Pessoa de Meia-Idade , Prolapso de Órgão Pélvico/patologia , Prolapso de Órgão Pélvico/cirurgia , Qualidade de Vida , Sacro/patologia , Útero/patologiaRESUMO
STUDY OBJECTIVE: The purpose of this study was to determine if there are any genetic changes with whole-exome sequencing associated with distal vaginal atresia. DESIGN: This was a retrospective genetics study of 5 patients who presented with distal vaginal atresia who were recruited between 2017 and 2018. Whole-exome sequencing was performed in each subject with distal vaginal atresia. Sanger sequencing was used to confirm the potential causative genetic mutation. SETTING: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. PARTICIPANTS AND MAIN OUTCOME MEASURES: The main outcome measure was the rare mutations potentially associated with distal vaginal atresia in 5 patients. RESULTS: A truncating mutation c.266delC (p.P89Rfs*5) in the T-box transcription factor 6 (TBX6) gene, which is highly expressed in the human vagina, was identified in 1 patient using whole-exome sequencing. The deletion of the 16p11.2 region containing the TBX6 locus has also been reported previously to have the clinical feature of Müllerian agenesis. This mutation was paternally inherited by the patient. This truncating mutation was absent from all of the databases we checked, suggesting that the variant is rare and pathogenic. CONCLUSION: We showed, to our knowledge, for the first time, that the mutation in TBX6 might be associated with human distal vaginal atresia.
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Anormalidades Congênitas/genética , Sequenciamento do Exoma/métodos , Proteínas com Domínio T/genética , Vagina/anormalidades , Adolescente , China , Feminino , Humanos , Lactente , Mutação com Perda de Função , Estudos RetrospectivosRESUMO
AIM: To investigate if intraoperative ultrasounds by laparoscopic and transvaginal ultrasonography (LUS and TVS) could improve enucleating the residual fibroids following laparoscopic myomectomy (LM). METHODS: From March to December 2016, 78 women with uterine fibroids underwent LM, LUS and TVS were applied to detect residual fibroids and to guide surgeons to enucleate them after the visible fibroids were removed during LM operation. RESULTS: The total number of residual fibroids found by LUS was 140, and the total number found by TVS was 127 following LM (Pâ¯=â¯0.03). LUS is statistically superior to TVS in the detection of residual fibroids in the anterior wall (Pâ¯=â¯0.004), in the detection of intramural fibroids (Pâ¯=â¯0.002), and in the detection of fibroids with a diameter ranging from 0.5 to 1â¯cm (Pâ¯=â¯0.002). According to the total number of enucleated fibroids by LM, patients were divided into three groups (Group 1: 2 to 4, Group 2: 5 to 7 and Group 3: ≥8 fibroid counts). The percentages of patients in each group with residual fibroids at the end of surgery were 22.2%, 51.9% and 66.7% respectively. CONCLUSIONS: Both LUS and TVS are beneficial to surgical treatment of fibroids by assisting enucleation of residual fibroids following LM, while LUS is more effective in localizing residual fibroids than TVS.
Assuntos
Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Cirurgia Assistida por Computador/métodos , Miomectomia Uterina , Adulto , Feminino , Humanos , Período Intraoperatório , Leiomioma/patologia , UltrassonografiaRESUMO
OBJECTIVE: To observe the effects of Spasfon on improving dilatation of cervix and promoting the progression of labor. METHODS: Ninety seven normal primiparae with cervical edema were randomly divided into Spasfon group (group A, n = 46) and atropine group (group B, n = 51) when the cervix dilated 2 - 3 cm. Group A was given 80 mg of Spasfon intravenously, and group B was injected atropine 0.5 mg into the cervix. RESULTS: (1) The mean time period from drug administration to full dilation of the cervix was (3.1 +/- 0.3) h in group A, and (4.4 +/- 0.4) h in group B (P < 0.01). (2) The disappearance ratio of cervical edema 2 h after drug administration in group A was 95.6%, while in group B it was 90.2% (P > 0.05); the mean dilatation of cervix between the 2 hours in group A was (4.3 +/- 0.2) cm, while in group B it was (2.5 +/- 0.3) cm (P < 0.01). (3) There were no obvious side effects in group A. While eight women in group B complained of thirst and 22 women had increased heart rate accompanied with elevated baseline FHR, which all recovered in about 60 minutes. (4) Vaginal delivery rate in group A was 95.7%, and 90.2% in group B (P > 0.05). (5) There was no statistically significant difference in the color of amniotic fluid, suffocation state and weight of the newborns between the two groups (P > 0.05). (6) There was no statistically significant difference in postpartum hemorrhage between the two groups, either (P > 0.05). CONCLUSION: Spasfon can effectively improve cervical dilatation during labor and it is well tolerated by both mother and newborn.