Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
FASEB J ; 37(7): e23052, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37352114

RESUMEN

The ion channels in sperm tail play an important role in triggering key physiological reactions, e.g., progressive motility, hyperactivation, required for successful fertilization. Among them, CatSper and KSper have been shown to be important ion channels for the transport of Ca2+ and K+ . Moreover, the voltage-gated proton channel Hv1, the sperm-specific sodium-hydrogen exchanger (sNHE), the epithelial sodium channel (ENaC), members of the temperature-sensitive TRP channel family, and the cystic fibrosis transmembrane regulator (CFTR) are also found in the flagellum. This review focuses on the latest advances in ion channels located at the flagellum, describes how they affect sperm physiological function, and summarizes some primary mutual regulation mechanism between ion channels, including PH, membrane potential, and cAMP. These ion channels may be promising targets for clinical application in infertility.


Asunto(s)
Canales de Calcio , Cola del Espermatozoide , Humanos , Masculino , Cola del Espermatozoide/metabolismo , Canales de Calcio/metabolismo , Semen/metabolismo , Espermatozoides/metabolismo , Transporte Iónico , Motilidad Espermática/fisiología
2.
Ecotoxicol Environ Saf ; 268: 115726, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37992646

RESUMEN

Exposure to metal mixtures may affect children's health but the conclusions are controversial. We aimed to investigate the associations of metal mixture exposure with children's physical and behavioral development. 15 metals were detected in the urine samples of 278 preschoolers aged 3-6 years from eastern China. Multiple linear models and restricted cubic splines were used to evaluate dose-response relationships between single metal and children's physical and behavioral development. The Bayesian Kernel Machine Regression (BKMR) models, the weighted quantile sum (WQS) models and Quantile G-Computation were applied to evaluate the joint effects of metal mixtures. The results showed that arsenic (As) was negatively associated with z score of height for age (HAZ) in individual-metal models [ß (95%CI): - 0.22 (-0.38, -0.06), P = 0.006]. Concerning children's behavioral development, multiple-metal models demonstrated a negative association with strontium (Sr) [ß (95%CI): - 0.82 (-1.38, -0.26), P = 0.004], and a positive association with tin (Sn) [ß (95%CI): 0.69 (0.16, 1.21), P = 0.010]. Notably, these associations remained significant or suggestive even after adjustments for multiple tests, sensitivity analyses, and application of different statistical models, including BKMR, WQS, and Quantile G-Computation. Furthermore, the study identified a negative joint effect of the metal mixture on HAZ, as demonstrated by BKMR and Quantile G-Computation models, with As playing an irreplaceable role in this observed impact. In summary, exposure to As appears to have adverse effects on HAZ, while exposure to Sn may hinder children's behavioral development. Conversely, exposure to Sr may have a protective effect on children's behavioral development. Additionally, the combined impact of metal mixtures is implicated in potentially impairing children's physical development, particularly in terms of HAZ.


Asunto(s)
Arsénico , Exposición a Riesgos Ambientales , Humanos , Niño , Preescolar , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Monitoreo Biológico , Teorema de Bayes , Metales/toxicidad , Metales/análisis , Arsénico/toxicidad , Arsénico/análisis , Estroncio/análisis , China
3.
Neural Plast ; 2023: 2741287, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38099081

RESUMEN

Background: Obsessive-compulsive disorder (OCD) is frequently treated using a combination of counseling, drugs, and, more recently various transcranial stimulation protocols, but all require several weeks to months for clinically significant improvement, so there is a need for treatments with faster onset. This study investigated whether an accelerated high-dose theta burst stimulation (ahTBS) protocol significantly improves the efficacy of OCD compared to traditional 1-Hz repetitive transcranial magnetic stimulation (rTMS) in the routine clinical setting. Method: Forty-five patients with OCD were randomized into two groups and treated with ahTBS or 1-Hz rTMS for 5 days. Patients were assessed at baseline at the end of treatment using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results: After 5 days of treatment, there was a significant decrease in Y-BOCS scores in both groups (p < 0.001), and the difference between the two groups was not statistically significant (group × time interaction, F = 1.90, p=0.18). There was also no statistically significant difference in other secondary outcome indicators, including depression, anxiety symptoms, and response rate. However, the ahTBS group had a greater trend in response rate. Neuropsychological testing showed no negative cognitive side effects of either treatment. Conclusion: Accelerated high-dose TBS is as safe and has comparable short-term efficacy to traditional 1-Hz rTMS for the clinical treatment of OCD. Further research is needed to explore optimal ahTBS parameters, validate the utility of this treatment modality, and identify factors predictive of rapid clinical response to guide clinical decision-making. This trial is registered with NCT05221632.


Asunto(s)
Trastorno Obsesivo Compulsivo , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Proyectos de Investigación , Trastorno Obsesivo Compulsivo/terapia , Pruebas Neuropsicológicas , Resultado del Tratamiento
4.
Anal Chem ; 94(38): 13076-13083, 2022 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-36106530

RESUMEN

CRISPR/Cas-based systems are highly attractive for developing next-generation diagnostic technologies because of their intrinsic merits such as simplicity, sensitivity, and specificity. However, currently, nucleic acid amplification procedures are still needed to achieve attomolar sensitivity in most CRISPR/Cas-based assays, which causes high cost, operation difficulty, and low efficiency. Herein, we combine the CRISPR/Cas12a-based assay and a single-microbead detection platform for one-step and amplification-free detection of DNA at the single-molecule level. By modifying DNA reporters on a biomimetic membrane-coated microbead, the activated Cas12a by targets will cleave these reporters and lighten the bead within 10 min. The method allows the detection of the target down to three copies in a 5 µL sample. Furthermore, we successfully apply this method for the specific identification of viral infection, foodborne bacteria, and DNA mutation in real samples without extra nucleic acid amplification. We believe that this approach offers new insights for developing CRISPR/Cas-based DNA assays in biomedical applications.


Asunto(s)
Sistemas CRISPR-Cas , Técnicas de Amplificación de Ácido Nucleico , Sistemas CRISPR-Cas/genética , ADN , Microesferas , Técnicas de Amplificación de Ácido Nucleico/métodos
5.
Anal Chem ; 94(37): 12822-12827, 2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-36067364

RESUMEN

Capture and analysis of circulating tumor cells (CTCs) from complex matrixes is pivotal for the prediction of cancer metastasis and personalized treatment of cancer. Herein, we propose a strategy for CTC capture by design and fabrication of a polyvalent aptamer network on an electrode surface, which can be further used for the sensitive analysis of CTCs. In our design, the polyvalent aptamer network, which is constructed via a rolling circle amplification reaction, can significantly enhance the cell-binding abilities. Meanwhile, tetrahedral DNA structures previously assembled on the electrode surface will promote the spatial orientation and reduce the steric hindrance effect of the cell capture, thus improving the cell capture efficiency. Importantly, a detectable electrochemical signal can be obtained without additional signal probes by means of target-induced allostery of the DNA hairpin structures. Further studies reveal that the electrochemical response is proportional to the logarithm of the CTC abundance ranging from 102 to 5 × 104 cell mL-1 with a low limit of detection of 23 cell mL-1. Moreover, the proposed capture strategy exhibits excellent stability and anti-interference in human whole blood, indicating its promising potential in clinical diagnosis.


Asunto(s)
Aptámeros de Nucleótidos , Células Neoplásicas Circulantes , Aptámeros de Nucleótidos/química , Línea Celular Tumoral , ADN , Electrodos , Humanos , Células Neoplásicas Circulantes/patología
6.
Anal Chem ; 94(5): 2383-2390, 2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35068136

RESUMEN

Analyzing single-cell phenotypes is increasingly required in biomedical studies, for non-genetic understanding of cellular activities and the biological significance of rare cell subpopulations. However, as compared to the genotypic analysis, single-cell phenotype analysis is technically more challenging. Herein, a tractable method that allows quantitative phenotyping of single cell is developed in this work, termed as the aptamer-mounted nest-PCR (Apt-nPCR). In specific, only two rounds of PCR reactions are required to complete the analysis, where aptamers (short oligonucleotides that bind to specific target molecules) are used as the recognition elements to bind antigens and also as the templates of nPCR for multiplexed and quantitative detection. So, quantitative information of these target antigens can be revealed by quantitative PCR analysis of these aptamers, which can thus be used to interpret cell phenotypes in a quantitative-to-qualitative way. By addressing two technical issues that are involved in single-cell phenotype analysis─multiplexed detection plus high sensitivity, we have shown the availability of this method for single-cell phenotyping. Therefore, the Apt-nPCR method may represent a tractable method to facilitate the single-cell phenotype analysis, which can be used as a complementary method against these single-cell genotyping methods in our daily research.


Asunto(s)
Aptámeros de Nucleótidos , Aptámeros de Nucleótidos/genética , Aptámeros de Nucleótidos/metabolismo , Reacción en Cadena de la Polimerasa
7.
Analyst ; 145(2): 613-618, 2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31782424

RESUMEN

Herein, an electrochemical method to detect histone acetyltransferases activity (HAT) has been developed based on the reduction of G-Quadruplex-Cu(ii) metalloenzyme activity. A G-quadruplex-Cu(ii) metalloenzyme has excellent peroxidase property, generating strong electrochemical signal. In the presence of HAT, it can catalyze substrate peptide acetylation and produce large amounts of Coenzyme A (CoA). The electrochemical signal of G-Quadruplex-Cu(ii) is weak due to the competitive combination between G-Quadruplex and CoA with Cu(ii), resulting in the direct quantitative detection of HAT. The detection limit for HAT is about 0.14 nM using this strategy and the cost is quite low since the developed assay method is label-free and antibody-free due to the use of low-cost DNA and Cu2+. Since this assay method can be employed to detect HAT in serum, it may be useful in disease diagnosis in the future.


Asunto(s)
Técnicas Biosensibles/métodos , Coenzima A/metabolismo , Cobre/metabolismo , G-Cuádruplex , Histona Acetiltransferasas/metabolismo , Fragmentos de Péptidos/metabolismo , Acetilación , Coenzima A/química , Cobre/química , Técnicas Electroquímicas , Humanos , Límite de Detección , Fragmentos de Péptidos/química
8.
Zhonghua Nan Ke Xue ; 26(12): 1074-1082, 2020 Dec.
Artículo en Zh | MEDLINE | ID: mdl-34898080

RESUMEN

OBJECTIVE: To explore the pathogenesis of lubrication disorder (LD), a most common type of female sexual dysfunction affecting women's physical health and conception, and find the therapeutic targets for its treatment and prevention. METHODS: We chose 3 LD patients and 3 healthy controls in Nanjing Maternal and Child Health Hospital, extracted their vaginal epithelial RNA for high-throughput miRNA sequencing, screened differentially expressed miRNAs for hierarchical cluster analysis, target gene prediction and gene ontology (GO) and KEGG pathway enrichment analyses. Finally, we verified the sequencing results by real-time fluorescent quantitative PCR. RESULTS: Totally 1 673 miRNAs were predicted by high-throughput sequencing and 64 likely to be the targets for the treatment of LD were screened, including 25 up-regulated more than 4 times and 39 down-regulated more than 4 times in the LD patients compared with the healthy controls. The neuron projection morphogenesis and AMPK signaling pathway were the most significant enrichment GO term and KEGG pathway. CONCLUSIONS: miRNAs are expressed differentially in LD patients. These miRNAs and target genes may be related to the occurrence of LD, and those that are expected to be the targets for the treatment of LD have important theoretical significance and potential application value.


Asunto(s)
MicroARNs , Niño , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lubrificación , MicroARNs/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal
9.
J Cell Physiol ; 234(5): 7012-7018, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30426492

RESUMEN

Genome-wide association studies (GWASs) showed that three single nucleotide polymorphisms (SNPs; rs10968576, rs1412239, and rs824248) in the leucine-rich repeat and Ig domain containing 2 (LINGO2) were associated with obesity or type 2 diabetes (T2D). We aimed to determine the influence of the LINGO2 variants on the gestational diabetes mellitus (GDM) risk. Thus, we performed a case-control study including 964 GDM cases and 1,021 controls to test the associations between the three LINGO2 variants (rs10968576, rs1412239, and rs824248) and susceptibility to GDM. Logistic regression analyses showed no significant association between LINGO2 variations (rs10968576 and rs1412239) and GDM susceptibility, but we observed that LINGO2 rs824248 A > T was significantly associated with an increased risk of GDM using the dominant model (TT/AT vs. AA: adjusted odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.05-1.51; p = 0.012) and the additive model (TT vs. AT vs. AA: adjusted OR = 1.16, 95% CI = 1.03-1.31; p = 0.016). In the additive model, a stronger risk effect of rs824248 was observed among obese women (prepregnancy body mass index [BMI] > 22 kg/m2 , adjusted OR = 1.34, 95% CI = 1.12-1.59) compared with that in lean women (prepregnancy BMI ≤ 22 kg/m2 , adjusted OR = 1.02 , 95% CI = 0.86-1.21; p = 0.029 for heterogeneity test). Further interactive analyses also detected a significant multiplicative interaction between rs824248 and prepregnancy BMI for the risk of GDM (p = 0.041). These findings indicate that LINGO2 rs824248 may serve as a susceptibility marker for GDM in Chinese females.


Asunto(s)
Diabetes Gestacional/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/etnología , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Embarazo , Medición de Riesgo , Factores de Riesgo
10.
J Sex Med ; 16(11): 1696-1707, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31551192

RESUMEN

INTRODUCTION: Recently, circular RNA (circRNA) has been proved to occupy a vital pathological position in many diseases by acting as microRNAs sponges. However, the role of circRNA in female sexual dysfunction (FSD), especially in lubrication disorders (LDs), remains unclear. AIM: The aim of this study was to detect circRNA expression in LDs, analyzed target genes, and pathways regulated by the differently expressed circRNAs. METHODS: In this study, next-generation sequencing was first conducted to produce circRNA expression profiles of FSD groups and normal control groups. Furthermore, differences in expression of 6 randomly selected circRNAs were confirmed through real-time quantitative polymerase chain reaction. Kyoto Encyclopedia of Genes and Genomes biological pathway analysis and Gene Ontology showed that immune processes and infection could be involved in the development of FSDs. MAIN OUTCOME MEASURE: CircRNA expression in vaginal epithelial tissue obtained from women with LDs have been detected. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes biological pathway analysis, and circRNA-microRNA interaction predictions were investigated. RESULTS: Totally, 7,746 circRNAs of vaginal epithelial tissue from women of 2 groups were sequenced. Preliminary judgment revealed that there were 73 circRNAs that have significant differential expression, including 53 downregulated circRNAs and 20 upregulated circRNAs. Research results also displayed that the majority of circRNAs has multiple binding sites of microRNAs, including miR-137, which has been reported to be linked to FSD. CLINICAL IMPLICATIONS: We predicted 10 circRNAs paired with hsa-miR-137-5p, but the mechanism of circRNA involvement in disease development remains to be further explored. STRENGTHS & LIMITATIONS: For the first time, the research disclosed the potential pathogenesis of LDs. However, we only analyzed the expression profile of circRNA in FSD, no specific mechanism was further confirmed or proposed. We still have a preliminary understanding, and more research is needed to explore the target of FSD treatment. CONCLUSION: The results suggest that circRNAs have different expression in the FSD groups and play a vital part in the occurrence and development of FSD. Zhang J, Xia H, Zhang A, et al. Circular RNA Expression Profiles in Vaginal Epithelial Tissue of Women With Lubrication Disorders. J Sex Med 2019;16:1696-1707.


Asunto(s)
ARN Circular/genética , Disfunciones Sexuales Fisiológicas/genética , Adulto , Regulación hacia Abajo , Femenino , Humanos , MicroARNs/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba
11.
Analyst ; 144(11): 3539-3545, 2019 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-31025665

RESUMEN

The formation of DNA self-assembled monolayers (SAMs) is one of the most popular ways to attach DNA molecules onto Au surfaces and is extensively used in many fields, especially in biosensing. However, the relatively poor stability of DNA SAMs (e.g., after long-term storage or under harsh environmental conditions) greatly limits their use in real applications. Herein, a new strategy is reported to protect the DNA SAMs by using a metal organic framework (MOF)-based exoskeleton. Taking electrochemical DNA (E-DNA) sensors as an example, we have systematically studied the stability of various DNA probes from the simple single-stranded DNA to a complex DNA nanostructure on the Au electrode surface. We have found that different DNA probes lead to various MOF profiles and the formed MOFs can be conveniently removed by simple acidic water rinse. Thanks to the exoskeleton, the stability of DNA SAMs is significantly enhanced and the DNA probes can be insulated from heat, nuclease, and varying ionic strengths, greatly extending the shelf-life of E-DNA sensors and indirectly improving their sensing performance. More importantly, the secondary structures of DNA probes can also be well preserved. The longstanding stability is of particular importance to biosensors; thus they can be facilely handled, transported, and stored in a resource-limited setting without compromising the analytical performance of biosensors.


Asunto(s)
Sondas de ADN/química , ADN/química , Estructuras Metalorgánicas/química , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Electrodos , Oro/química
12.
Mikrochim Acta ; 186(1): 48, 2019 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-30610460

RESUMEN

The authors describe a turn-off fluorometric method for the determination of the activity of the T4 polynucleotide kinase (T4 PNK). It is based on the use of DNA-templated silver nanoclusters (AgNCs). DNA probes with terminal 5' hydroxy groups are used as substrates for DNA phosphatases. If subsequently treated with T4 PNK and Lambda exonuclease (λ exo), the AgNC DNA probes with a modified C-rich sequence and the G-rich sequence is separated. Upon their separation, the strong fluorescence (with excitation/emission maxima at 580/650 nm) that is caused by the proximity of the G-rich region and the C-rich region in the AgNCs decreases sharply. This enabled the fluorometric kinetic determination of the activity of T4 PNK. The assay is characterized by a wide linear range (from 0.01 to 12.5 U·mL-1), a low detection limit (0.01 U·mL-1) and short assay time (typically 60 min). This makes it a promising tool for use in studying processes related to DNA phosphorylation, in drug discovery and in diagnostics. Graphical abstract A turn-off fluorometric method for the determination of the activity of the T4 polynucleotide kinase (T4 PNK) has been developed. It is based on the use of DNA-templated silver nanoclusters (AgNCs). This makes it a promising tool for use in studying processes related to DNA phosphorylation, in drug discovery and in diagnostics.


Asunto(s)
Bacteriófago T4/enzimología , ADN/química , Fluorometría/métodos , Nanopartículas del Metal/química , Sondas Moleculares/química , Polinucleótido 5'-Hidroxil-Quinasa/metabolismo , ADN/metabolismo , Cinética , Fosforilación , Polinucleótido 5'-Hidroxil-Quinasa/análisis , Plata
13.
Mikrochim Acta ; 187(1): 22, 2019 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-31807960

RESUMEN

A method is described for the determination of the CCAAT/enhancer binding protein alpha (C/EBPα) which is a regulator in adipocyte differentiation. The method is based on quenching of the red fluorescence (with excitation/emission maxima at 548/562 nm) of Cy3-labeled DNA if it becomes adsorbed on positively charged gold nanoparticles (AuNPs). Fluorescently labeled dsDNA that can bind C/EBPα is introduced as a fluorescent probes. The dsDNA is electrostatically adsorbed on the positively charged AuNPs to quench their fluorescence. In the presence of C/EBPα, it will bind dsDNA which then diffuses away. The fluorescence of the AuNPs becomes restored. The fluorescent signal increases linearly in the 0.05 to 600 ng·mL-1 µM C/EBPα concentration range, and the detection limit is 29 pg·mL-1. The method is specific and was applied to analyze cell lysates and in-situ. Graphical abstractSchematic representation of a fluorometric method for determination of the CCAAT/enhancer binding protein alpha (C/EBPα). Fluorescently labeled dsDNA that can bind C/EBPα is introduced as a fluorescent probes. The dsDNA is electrostatically adsorbed on the positively charged AuNPs to quench their fluorescence. In the presence of C/EBPα, it will bind dsDNA which then diffuses away. The fluorescence of the AuNPs becomes restored.


Asunto(s)
Proteína alfa Potenciadora de Unión a CCAAT/análisis , Sondas de ADN/química , Colorantes Fluorescentes/química , Fluorometría/métodos , Oro/química , Nanopartículas del Metal/química , Proteína alfa Potenciadora de Unión a CCAAT/química , Línea Celular , Estudios de Factibilidad , Humanos
14.
Zhonghua Nan Ke Xue ; 24(6): 516-519, 2018 Jun.
Artículo en Zh | MEDLINE | ID: mdl-30173456

RESUMEN

OBJECTIVE: Human papilloma virus (HPV) is a necessary cause of cervical cancer and is also closely related to penile cancer, oropharyngeal cancer, and anal cancer in males. However, few studies are reported on male HPV. This study aimed to investigate HPV infection of the external genitalia in men whose female partners have cervical HPV infection. METHODS: We collected the relevant data on the male outpatients whose partners had cervical HPV infection in our Department of Urology and Andrology from August to December 2016. We obtained samples with nylon swabs from the glans penis, corona, inner layer of the prepuce and penile body and detected different types of HPV infection using the Hybribio HPV typing kit, PCR and membrane hybridization. RESULTS: Valid data were collected from 140 males, which showed 83.5% of HPV infection of the external genitalia, including 60 cases of HPV6 (43.2%), 27 cases of HPV16 (19.4%), 14 cases of HPV39 (10.1%), 13 cases of HPV18 (9.4%), 13 cases of HPV58 (9.4%), and 13 cases of HPV52 (9.4%). Redundant prepuce was found in 75.5% of the males, but there was no statistically significant difference in the incidence rate of HPV infection between the normal and redundant prepuce groups (P > 0.05). CONCLUSIONS: Men who have the female partners with positive cervical HPV are at high risk of HPV infection and therefore need to be screened and treated so as to reduce HPV infection in both sexes.


Asunto(s)
Enfermedades de los Genitales Femeninos/virología , Enfermedades de los Genitales Masculinos/virología , Infecciones por Papillomavirus/diagnóstico , Pene/virología , Femenino , Prepucio/virología , Papillomavirus Humano 16/aislamiento & purificación , Humanos , Masculino , Papillomaviridae/aislamiento & purificación , Neoplasias del Pene/virología , Pene/anomalías , Fimosis/virología , Reacción en Cadena de la Polimerasa , Parejas Sexuales , Manejo de Especímenes , Neoplasias del Cuello Uterino/virología
15.
Mol Genet Genomics ; 291(6): 2215-2224, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27681254

RESUMEN

To better understand the molecular aetiology of type 2 diabetes mellitus-associated erectile dysfunction (T2DMED) and to provide candidates for further study of its diagnosis and treatment, this study was designed to investigate differentially expressed microRNAs (miRNAs) in the corpus cavernosum (CC) of mice with T2DMED using GeneChip array techniques (Affymetrix miRNA 4.0 Array) and to predict target genes and signalling pathways regulated by these miRNAs based on bioinformatic analysis using TargetScan, the DAIAN web platform and DAVID. In the initial screening, 21 miRNAs appeared distinctly expressed in the T2DMED group (fold change ≥3, p ≤ 0.01). Among them, the differential expression of miR-18a, miR-206, miR-122, and miR-133 were confirmed by qRT-PCR (p < 0.05 and FDR <5 %). According to bioinformatic analysis, the four miRNAs were speculated to play potential roles in the mechanisms of T2DMED via regulating 28 different genes and several pathways, including apoptosis, fibrosis, eNOS/cGMP/PKG, and vascular smooth muscle contraction processes, which mainly focused on influencing the functions of the endothelium and smooth muscle in the CC. IGF-1, as one of the target genes, was verified to decrease in the CCs of T2DMED animals via ELISA and was confirmed as the target of miR-18a or miR-206 via luciferase assay. Finally, these four miRNAs deserve further confirmation as biomarkers of T2DMED in larger studies. Additionally, miR-18a and/or miR-206 may provide new preventive/therapeutic targets for ED management by targeting IGF-1.


Asunto(s)
Biología Computacional/métodos , Diabetes Mellitus Tipo 2/complicaciones , Disfunción Eréctil/genética , Perfilación de la Expresión Génica/métodos , MicroARNs/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Animales , Modelos Animales de Enfermedad , Disfunción Eréctil/fisiopatología , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Ratones , Pene/metabolismo , Pene/fisiopatología
16.
Zhonghua Nan Ke Xue ; 22(10): 882-885, 2016 Oct.
Artículo en Zh | MEDLINE | ID: mdl-29278468

RESUMEN

OBJECTIVE: To investigate the relationship between the abnormal sperm DNA methylation level and early spontaneous abortion. METHODS: We randomly selected 98 males who met the inclusion criteria and whose wives suffered from unexplained abortion or embryo abortion, and included another 46 normal healthy men present for pre-pregnancy check-up as controls. We examined the semen quality and sperm morphology, obtained the sperm DNA fragmentation index (DFI) by modified sperm chromatin dispersion, and measured the sperm DNA methylation level using the methylated DNA quantification kit and the colorimetric method. RESULTS: Compared with the normal controls, the men in the unexplained abortion group showed a significantly lower rate of big-halo sperm (ï¼»45.50 ± 26.27ï¼½ vs ï¼»36.49 ± 23.06ï¼½%, P = 0.038), a higher rate of abnormal-head sperm (ï¼»77.08± 12.21ï¼½ vs ï¼»81.09± 10.89ï¼½%, P = 0.049), and a lower level of sperm DNA methylation (ï¼»0.47 ± 0.33ï¼½ vs ï¼»0.36 ± 0.26ï¼½ ng/µl, P = 0.035). The sperm DNA methylation level was positively correlated with the percentage of big-halo sperm (OR=0.546, P<0.01). Multivariate regression analysis manifested that sperm head abnormality was an independent risk factor of early spontaneous abortion or embryo abortion (OR=1.032, P = 0.049), while the high methylation level was protective factor against early spontaneous abortion or embryo abortion (OR=0.244, P = 0.03). CONCLUSIONS: The abnormal level of sperm DNA methylation may be one of the important reasons for early spontaneous abortion or embryo abortion.


Asunto(s)
Aborto Espontáneo/etiología , Metilación de ADN , Análisis de Semen , Cabeza del Espermatozoide/patología , Estudios de Casos y Controles , Fragmentación del ADN , Femenino , Humanos , Masculino , Embarazo , Factores de Riesgo
17.
Cell Physiol Biochem ; 37(4): 1513-26, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26513665

RESUMEN

BACKGROUND/AIMS: Erectile dysfunction (ED) in aged people remains a topic of interest to andrological physicians. Long non-coding RNAs (lncRNAs), which form the largest group of non-coding RNAs, have been shown to regulate various biological processes. The function of lncRNAs in age-related erectile dysfunction (A-ED) pathogenesis remains poorly understood. METHODS: This study aims to assess the differential expression profiles of mRNAs and lncRNAs between A-ED and normal control (NC) samples. Using a second-generation lncRNA microarray, we detected a total of 8,744 lncRNAs and 13,585 coding transcripts. RESULTS: We identified 608 up-regulated and 406 down-regulated lncRNAs in A-ED compared with NC samples, by setting a filter of fold-change >2.0. Gene Ontology and pathway analysis revealed that a muscle contraction disorder induced by abnormal ion channels might play a critical role in the pathogenesis of A-ED. CONCLUSION: Our results show significantly altered expression profiles of lncRNAs and mRNAs between A-ED and NC. This study may provide information for further research on A-ED and may be helpful for finding a new therapeutic target for A-ED.


Asunto(s)
Envejecimiento , Disfunción Eréctil/genética , ARN Largo no Codificante/genética , Animales , Regulación hacia Abajo , Disfunción Eréctil/patología , Perfilación de la Expresión Génica , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba
18.
Int J Gynecol Cancer ; 25(3): 356-62, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25695542

RESUMEN

OBJECTIVE: To evaluate the association of tumor-derived matrix metalloproteinase 2 (MMP-2) and stromal-derived MMP-2 expression with the prognosis of patients with ovarian cancer, a meta-analysis study was performed, which was aimed to comprehensively review the evidence of MMP-2 as prognostic biomarkers in ovarian cancers. METHODS: All relevant studies were searched in PubMed and Web of Science until May 30, 2014. Hazard ratios (HRs) with their 95% confidence intervals (CIs) were used to assess the association between MMP-2 expression (tumor-derived or stromal-derived) and prognosis of patients with ovarian cancer. Pooled odds ratios (ORs) and their 95% CIs were used to assess the correlation of MMP-2 expression with the clinicopathological features of patients with ovarian cancer. RESULTS: A total of 965 patients in 8 studies were included in this analysis. Among them, tumor-derived and stromal-derived MMP-2 expression was detected in 7 and 5 articles, respectively. The results revealed that ovarian cancer patients with positive tumor-derived MMP-2 expression showed a worse prognosis than did the ones with negative tumor-derived MMP-2 expression (HR, 1.52; 95% CI, 1.06-2.20). However, ovarian cancer patients with positive stromal-derived MMP-2 expression had not. In addition, we also found that tumor-derived MMP-2 expression was associated with distant metastasis (absent vs present; pooled OR, 4.52; 95% CI, 1.56-13.09; P = 0.001). CONCLUSIONS: These results suggested that positive tumor-derived MMP-2 expression could predict a lower overall survival rate and could be an independent dangerous prognostic factor in patients with ovarian cancer.


Asunto(s)
Biomarcadores de Tumor/análisis , Metaloproteinasa 2 de la Matriz/análisis , Neoplasias Ováricas/enzimología , Células del Estroma/enzimología , Progresión de la Enfermedad , Femenino , Humanos , Metástasis de la Neoplasia , Neoplasias Ováricas/patología , Pronóstico , Tasa de Supervivencia
19.
J Sex Med ; 11(4): 909-919, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24754329

RESUMEN

INTRODUCTION: The Female Sexual Function Index (FSFI) remains the most widely used scale for screening female sexual dysfunction (FSD), and the Chinese Version of the FSFI (CVFSFI) has been validated, but cutoff scores for the CVFSFI to distinguish between cases and noncases have not been developed, so the real prevalence of FSD in China is unknown. AIM: To establish clinical cutoff scores for the CVFSFI and to evaluate the prevalence of FSD in urban Chinese women. METHODS: A cross-sectional study was conducted between June and December 2011. A total of 586 (age range of 22-60 years) women participated in the study. Receiving operating characteristic curve and classification and regression trees methodology were combined to establish clinical cutoff scores for the CVFSFI. The cutoff scores we developed were used to determine the prevalence of FSD in urban Chinese women. MAIN OUTCOME MEASURES: The prevalence of FSD based on cutoff scores developed herein. RESULTS: The optimal CVFSFI cutoff score for the FSFI total score was 23.45 (sensitivity = 66.9%; specificity = 72.7%; area under curve [AUC] = 0.75). The cutoff score for each domain was also established as follows: ≤2.7 low desire (sensitivity = 55.2%; specificity = 78.3%; AUC = 0.73); ≤3.15 arousal disorder (sensitivity = 62.1%; specificity = 76.9%; AUC = 0.74); ≤4.05 lubrication disorder (sensitivity = 86.4%; specificity = 69.8%; AUC = 0.85); ≤3.8 orgasm disorder (sensitivity = 83.3%; specificity = 74.2%; AUC = 0.85); and ≤3.8 sexual pain (sensitivity = 65.4%; specificity = 80.6%; AUC = 0.79). Using these cutoff scores, we determined the prevalence for FSD, low desire, arousal disorder, lubrication disorder, orgasm disorder, and sexual pain to be 37.6%, 23.6%, 25.4%, 36.8%, 30.6%, and 21.8% in urban Chinese women, respectively. CONCLUSIONS: The present data may suggest that urban Chinese women might have a lower FSD prevalence than women from some other countries; however, further study to achieve a better understanding of its epidemiology in China is a high necessity.


Asunto(s)
Disfunciones Sexuales Fisiológicas/epidemiología , Disfunciones Sexuales Psicológicas/epidemiología , Adulto , Nivel de Alerta/fisiología , China/epidemiología , Métodos Epidemiológicos , Femenino , Humanos , Persona de Mediana Edad , Conducta Sexual , Disfunciones Sexuales Fisiológicas/diagnóstico , Disfunciones Sexuales Psicológicas/diagnóstico , Salud Urbana , Adulto Joven
20.
Zhonghua Nan Ke Xue ; 20(8): 734-7, 2014 Aug.
Artículo en Zh | MEDLINE | ID: mdl-25195372

RESUMEN

Epigenetics comprises the modifications made in gene expressions without changing the DNA sequence itself. Significant epigenetic changes take place during spermatogenesis and fertilization and exert direct influences on embryogenesis. This article provides an overview of the latest researches on epigenetics of male germ cells and a brief discussion on the correlation of sperm with embryogenesis in four aspects: DNA methylation, histone modification, regulation of non-coding RNAs, and genomic imprinting.


Asunto(s)
Desarrollo Embrionario , Epigénesis Genética , Espermatozoides , Animales , Metilación de ADN , Impresión Genómica , Histonas/metabolismo , Humanos , Masculino
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA