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1.
J Cell Biochem ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898364

RESUMO

The study aimed to investigate the expression and function of bladder cancer (BC) long noncoding RNAs (lncRNAs) using a high-throughput platform. High-throughput sequencing was used to compare the expression profiles of lncRNA in BC and adjacent normal tissues. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in situ hybridization, gene ontology, and Kyoto Encyclopedia of Genes and Genomes analysis were performed to verify differential expression of lncRNA. The effect of lncRNA overexpression on cellular proliferation, apoptosis, migration, and invasion was analyzed following the transfection of lncRNA overexpressing lentivirus into 5637 and T24 cell lines. The overexpressing cells were subcutaneously injected into nude mice to evaluate their effects on tumor growth. Tumor-associated RNA-binding proteins of lncRNA were analyzed by RNA pull-down combined with mass spectrometry. A total of 93 lncRNA genes were upregulated and 352 lncRNA genes were downregulated in the tissues of patients with BC. Of which, we investigated the function of downregulated lnc-MUC20-9. Overexpression of lnc-MUC20-9 in 5637 and T24 cells resulted in decreased tumor cell viability and cell clones, decreased migration and invasion, and increased apoptosis. Similarly, nude mice bearing lnc-MUC20-9 overexpressing tumor cells exhibited smaller tumor size and volume than that of mice bearing control cells. Mass spectrometry analysis showed that lnc-MUC20-9 binds to ROCK1, an oncogene whose expression was decreased in lnc-MUC20-9 overexpressing cells. The study revealed that lnc-MUC20-9 has the function of inhibiting tumor growth, migration, and invasion. In BC cells, lnc-MUC20-9 binds to ROCK1 and may be involved in lnc-MUC20-9-mediated tumor suppressor function, which might be potential therapeutic targets for BC.

2.
Elife ; 82019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31290742

RESUMO

Mechanical load of the skeleton system is essential for the development, growth, and maintenance of bone. However, the molecular mechanism by which mechanical stimuli are converted into osteogenesis and bone formation remains unclear. Here we report that Piezo1, a bona fide mechanotransducer that is critical for various biological processes, plays a critical role in bone formation. Knockout of Piezo1 in osteoblast lineage cells disrupts the osteogenesis of osteoblasts and severely impairs bone structure and strength. Bone loss that is induced by mechanical unloading is blunted in knockout mice. Intriguingly, simulated microgravity treatment reduced the function of osteoblasts by suppressing the expression of Piezo1. Furthermore, osteoporosis patients show reduced expression of Piezo1, which is closely correlated with osteoblast dysfunction. These data collectively suggest that Piezo1 functions as a key mechanotransducer for conferring mechanosensitivity to osteoblasts and determining mechanical-load-dependent bone formation, and represents a novel therapeutic target for treating osteoporosis or mechanical unloading-induced severe bone loss.

3.
Phytomedicine ; 56: 83-93, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30668357

RESUMO

BACKGROUND: Cardiac atrophy and reduced cardiac distensibility have been reported following space flight. Cardiac function is correspondingly regulated in response to changes in loading conditions. Panax quinquefolium saponin (PQS) improves ventricular remodeling after acute myocardial infarction by alleviating endoplasmic reticulum stress and Ca2+overload. However, whether PQS can ameliorate cardiac atrophy following exposure to simulated microgravity remains unknown. PURPOSE: To explore the protective role of PQS in cardiac remodeling under unloading conditions and its underlying mechanisms. METHODS: Hindlimb unloading (HU) model was used to simulate unloading induced cardiac remodeling. Forty-eight male rats were randomly assigned to four groups, including control, PQS, HU and HU + PQS. At 8 weeks after the experiment, cardiac structure and function, serum levels of Creatine Kinase-MB (CK-MB), Cardiactroponin T (cTnT), ischemia modified albumin (IMA), and cardiomyocyte apoptosis were measured. Network pharmacology analysis was used to predict the targets of the six major constituents of PQS, and the signaling pathways they involved in were analyzed by bioinformatics methods. Changes in the key proteins involved in the protective effects of PQS were further confirmed by Western Blot. RESULTS: Simulated microgravity led to increases in serum levels of CK-MB, cTnT and IMA, remodeling of cardiac structure, impairment of cardiac function, and increased cardiomyocyte apoptosis as compared with control. PQS treatment significantly reduced serum levels of CK-MB, cTnT and IMA, improved the impaired cardiac structure and function, and decreased cardiomyocyte apoptosis induced by unloading. The activation of AMPK and inhibition of Erk1/2 and CaMKII/HDAC4 were demonstrated in the cardiocytes of HU rats after PQS treatment. CONCLUSION: PQS provides protection against cardiac remodeling induced by simulated microgravity, partly resulting from changes in the signaling pathways related to energy metabolism reduction, calcium overloading and cell apoptosis.


Assuntos
Cardiotônicos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Saponinas/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Ausência de Peso/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/sangue , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Infarto do Miocárdio/etiologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Albumina Sérica/análise , Albumina Sérica Humana , Transdução de Sinais/efeitos dos fármacos
4.
DNA Cell Biol ; 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30362823

RESUMO

There is a perception that long noncoding RNA (lncRNA) has relationship with carcinogenesis. Many studies have previously identified and validated that the section of chromosome 11p13 is associated with high incidence of tumor. In this study, we investigated a new lncRNA, named lncPRRG4-4, mapped to 11p13 and suspected that lncPRRG4-4 was a potential lung cancer-related gene. To explore its role in carcinogenesis, we first demonstrated that lncPRRG4-4 was upregulated in lung cancer tissues compared with adjacent nontumor tissues and functioned as an oncogene in lung cancer cells. The lncPRRG4-4 was significantly upregulated in lung cancer tissues compared with adjacent normal counterparts (mean ± standard deviation: 0.12 ± 0.84 vs. 0.05 ± 0.22; p < 0.001). Patients with metastasis exhibited high levels of lncPRRG4-4 expression than those without metastasis in both the southern samples (p = 0.045) and eastern samples (p = 0.030), total samples (p = 0.004). In addition, downregulation of lncPRRG4-4 expression inhibited lung cancer proliferation, viability, migration, and invasion ability, arrested cell cycle, facilitated apoptosis, and vice versa. Taken together, these observations suggested that the lncPRRG4-4 functions as an oncogene in lung cancer cells.

5.
Pathol Res Pract ; 214(6): 857-861, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29709443

RESUMO

Antisense RNA (AS) is a type of long non-coding RNAs that functions as a post-transcriptional regulatory element on regulating parental coding gene expression via directly binding to complementary mRNA sequences. We aimed to investigate the effect of the AS to FEZF1 gene on non-small cell lung cancer (NSCLC) development. The expression level of lncRNA FEZF-AS1 and FEZF1 was determined by the quantitative Real-time PCR in 160 cases of NSCLC tissues and their adjacent non-tumour tissues. We found that lncRNA FEZF-AS1 was significantly up-regulated in tumour tissues when compared to the adjacent non-cancerous tissues (P = 0.001), and it's high expression correlated with advanced stages (P = 0.002) and Tumour Family History (P = 0.029). Meanwhile, In 58 cases of NSCLC tissues the expression of lncRNA FEZF-AS1 was positively associated with that of FEZF1expression (r = 0.8810, p = 1.6575E-20). By GEPIA database analysis, we also found that the expression of lncRNA FEZF-AS1 and FEZF1 were significantly higher in tumour tissues than those of the adjacent non-cancerous tissues in 969 NSCLC patients (P < 0.05), and lncRNA FEZF-AS1 was positively correlated with FEZF1 (r = 0.90, P < 0.001). These results suggest that lncRNA FEZF-AS1 relate to the progression of lung cancer patients and it may be a potential target for cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , RNA Antissenso/biossíntese , Fatores de Transcrição/biossíntese , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , RNA Antissenso/genética , Proteínas Repressoras , Fatores de Transcrição/genética , Regulação para Cima
6.
Mol Cell ; 68(1): 171-184.e6, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28985503

RESUMO

A substantial fraction of eukaryotic transcripts are considered long non-coding RNAs (lncRNAs), which regulate various hallmarks of cancer. Here, we discovered that the lncRNA HOXB-AS3 encodes a conserved 53-aa peptide. The HOXB-AS3 peptide, not lncRNA, suppresses colon cancer (CRC) growth. Mechanistically, the HOXB-AS3 peptide competitively binds to the ariginine residues in RGG motif of hnRNP A1 and antagonizes the hnRNP A1-mediated regulation of pyruvate kinase M (PKM) splicing by blocking the binding of the ariginine residues in RGG motif of hnRNP A1 to the sequences flanking PKM exon 9, ensuring the formation of lower PKM2 and suppressing glucose metabolism reprogramming. CRC patients with low levels of HOXB-AS3 peptide have poorer prognoses. Our study indicates that the loss of HOXB-AS3 peptide is a critical oncogenic event in CRC metabolic reprogramming. Our findings uncover a complex regulatory mechanism of cancer metabolism reprogramming orchestrated by a peptide encoded by an lncRNA.


Assuntos
Transformação Celular Neoplásica/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Peptídeos/genética , RNA Longo não Codificante/genética , Processamento Alternativo , Motivos de Aminoácidos , Animais , Ligação Competitiva , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Éxons , Células HeLa , Ribonucleoproteína Nuclear Heterogênea A1 , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Peptídeos/antagonistas & inibidores , Peptídeos/metabolismo , Ligação Proteica , Mapeamento de Interação de Proteínas , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
8.
J Assist Reprod Genet ; 33(9): 1239-46, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27364628

RESUMO

PURPOSE: The aim of this study is to investigate the relationships among reactive oxygen species (ROS) elevation, histone transition, and seminal cytokine concentrations. METHODS: Total levels of ROS in semen samples from 6560 men were measured. From this sample, 118 cases with high ROS and 106 controls were recruited. Basic semen parameters and histone-to-protamine ratios were analyzed, 400 semen cytokine and receptor alterations were assayed by protein chip, and finally 18 cytokines were validated in each sample using a Bio-Plex Cytokine assay. RESULTS: The results showed that the seminal ROS concentration was associated with abnormalities in the sperm histone transition. Compared with controls, 93 cytokines had significant alterations in the high ROS cases, with 14 of them further verified in individual samples. The concentrations of CXCL5, CXCL16, CXCL8, IL-1b, IL-10, CSF3, CCL3, and TNF-α were significantly correlated with the histone transition ratio. In addition, IL-16 showed significantly different concentrations in controls, normal semen with high ROS levels, and abnormal semen with high ROS levels. CONCLUSIONS: Semen ROS are associated with abnormalities in sperm histone transition. CXCL5, CXCL8, IL-16, CCL8, CCL22, CCL20, CXCL16, IL-1B, IL-6, IL-7, IL-10, CSF3, CCL3, CCL4, and TNF-α all have elevated concentrations in semen with high ROS levels. These data might help to explain the mechanisms behind the increase in the levels of ROS and seminal cytokines and their relationship with defective spermatogenesis.


Assuntos
Citocinas/genética , Histonas/metabolismo , Infertilidade Masculina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adulto , Citocinas/biossíntese , Humanos , Infertilidade Masculina/patologia , Masculino , Protaminas/metabolismo , Motilidade Espermática/genética , Espermatogênese/genética , Espermatozoides/metabolismo , Espermatozoides/patologia
9.
J Assist Reprod Genet ; 33(5): 581-588, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27052831

RESUMO

PURPOSE: As a powerful technology for genome engineering, the CRISPR/Cas system has been successfully applied to modify the genomes of various species. The purpose of this study was to evaluate the technology and establish principles for the introduction of precise genetic modifications in early human embryos. METHODS: 3PN zygotes were injected with Cas9 messenger RNA (mRNA) (100 ng/µl) and guide RNA (gRNA) (50 ng/µl). For oligo-injections, donor oligo-1 (99 bp) or oligo-2 (99 bp) (100 ng/µl) or dsDonor (1 kb) was mixed with Cas9 mRNA (100 ng/µl) and gRNA (50 ng/µl) and injected into the embryos. RESULTS: By co-injecting Cas9 mRNA, gRNAs, and donor DNA, we successfully introduced the naturally occurring CCR5Δ32 allele into early human 3PN embryos. In the embryos containing the engineered CCR5Δ32 allele, however, the other alleles at the same locus could not be fully controlled because they either remained wild type or contained indel mutations. CONCLUSIONS: This work has implications for the development of therapeutic treatments of genetic disorders, and it demonstrates that significant technical issues remain to be addressed. We advocate preventing any application of genome editing on the human germline until after a rigorous and thorough evaluation and discussion are undertaken by the global research and ethics communities.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Doenças Genéticas Inatas/genética , Receptores CCR5/genética , Reparo do DNA por Junção de Extremidades , Resistência à Doença/genética , Embrião de Mamíferos , Desenvolvimento Embrionário , Fertilização , Edição de Genes/ética , Doenças Genéticas Inatas/prevenção & controle , Humanos , Análise de Sequência de DNA
10.
Biomed Res Int ; 2016: 1765624, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27066497

RESUMO

BACKGROUND: Diverticulum, one of the long-term sequelae of cesarean section, can cause abnormal uterine bleeding and increase the risk of uterine scar rupture. In this study, we aimed to evaluate the efficacy of combined laparoscopic and hysteroscopic repair, a newly occurring method, treating post-cesarean section uterine scar diverticulum. METHODS: Data relating to 40 patients with post-cesarean section uterine diverticulum who underwent combined laparoscopic and hysteroscopic repair were retrospectively analyzed. Preoperative clinical manifestations, size of uterine defects, thickness of the lower uterine segment (LUS), and duration of menstruation were compared with follow-up findings at 1, 3, and 6 months after surgery. RESULTS: The average preoperative length and width of uterine diverticula and thickness of the lower uterine segment were recorded and analyzed. The average durations of menstruations at 1, 3, and 6 months after surgery were significantly shorter than the preoperative one (p < 0.05), respectively. At 6 months after surgery, the overall success improvement rate of surgery was 90% (36/40). Three patients (3/40 = 7.5%) developed partial improvement, and 1/40 (2.5%) was lost to follow-up. CONCLUSIONS: Our findings showed that combined treatment with laparoscopy and hysteroscopy was an effective method for the repair of post-cesarean section uterine diverticulum.


Assuntos
Cesárea/efeitos adversos , Divertículo/cirurgia , Histeroscopia/métodos , Histeroscopia/estatística & dados numéricos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Doenças Uterinas/cirurgia , Adulto , Feminino , Humanos , Histeroscopia/efeitos adversos , Laparoscopia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
PLoS One ; 10(7): e0131128, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26131765

RESUMO

Human-induced pluripotent stem cells (iPSCs) are derived from differentiated somatic cells using defined factors and provide a renewable source of autologous cells for cell therapy. Many reprogramming methods have been employed to generate human iPSCs, including the use of integrating vectors and non-integrating vectors. Maintenance of the genomic integrity of iPSCs is highly desirable if the cells are to be used in clinical applications. Here, using the Affymetrix Cytoscan HD array, we investigated the genomic aberration profiles of 19 human cell lines: 5 embryonic stem cell (ESC) lines, 6 iPSC lines derived using integrating vectors ("integrating iPSC lines"), 6 iPSC lines derived using non-integrating vectors ("non-integrating iPSC lines"), and the 2 parental cell lines from which the iPSCs were derived. The genome-wide copy number variation (CNV), loss of heterozygosity (LOH) and mosaicism patterns of integrating and non-integrating iPSC lines were investigated. The maximum sizes of CNVs in the genomes of the integrating iPSC lines were 20 times higher than those of the non-integrating iPSC lines. Moreover, the total number of CNVs was much higher in integrating iPSC lines than in other cell lines. The average numbers of novel CNVs with a low degree of overlap with the DGV and of likely pathogenic CNVs with a high degree of overlap with the ISCA (International Symposium on Computer Architecture) database were highest in integrating iPSC lines. Different single nucleotide polymorphisms (SNP) calls revealed that, using the parental cell genotype as a reference, integrating iPSC lines displayed more single nucleotide variations and mosaicism than did non-integrating iPSC lines. This study describes the genome stability of human iPSCs generated using either a DNA-integrating or non-integrating reprogramming method, of the corresponding somatic cells, and of hESCs. Our results highlight the importance of using a high-resolution method to monitor genomic aberrations in iPSCs intended for clinical applications to avoid any negative effects of reprogramming or cell culture.


Assuntos
Técnicas de Reprogramação Celular , Reprogramação Celular , Variações do Número de Cópias de DNA , Instabilidade Genômica , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Cultivadas , Heterozigoto , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Mosaicismo , Polimorfismo de Nucleotídeo Único
12.
Fertil Steril ; 101(1): 51-57.e1, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24112532

RESUMO

OBJECTIVE: To investigate the association between smoking, semen quality, and the histone-to-protamine transition ratio in mature sperm. DESIGN: Biochemical and molecular analysis in human samples and a cell line. SETTING: Andrology laboratory in a university-affiliated hospital. PATIENT(S): Semen samples from 147 heavy smokers and 175 nonsmokers receiving infertility treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Basic semen parameters, histone-to-protamine ratios, and number of sperm cells with abnormal histone transition were calculated. The relative messenger RNA (mRNA) expression levels of protamine 1 and protamine 2 were assayed in human sperm and in TM3 cells exposed to cigarette smoke condensate. T tests, Spearman tests, and nonparametric Mann-Whitney U tests were used to detect significant differences. RESULT(S): Normozoospermic smokers had significantly higher abnormalities than their nonsmoking counterparts. Sperm histone replacement abnormalities were found to be closely correlated with sperm motility, viability, concentration, counts, and cotinine levels. The ratios of protamine 1 to protamine 2 mRNA expression significantly increased in heavy smokers and in TM3 cells treated with cigarette smoke condensate. CONCLUSION(S): Smoking is strongly associated with abnormalities in histone-to-protamine transition and with alteration of protamine mRNA expression in human sperm.


Assuntos
Histonas/metabolismo , Protaminas/metabolismo , Fumar/efeitos adversos , Fumar/metabolismo , Espermatozoides/anormalidades , Espermatozoides/metabolismo , Adulto , Animais , Células Cultivadas , Humanos , Masculino , Camundongos , RNA Mensageiro/metabolismo , Sêmen/metabolismo , Motilidade Espermática/fisiologia
13.
Diagn Pathol ; 8: 94, 2013 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-23773344

RESUMO

UNLABELLED: Extranodal NK/T cell lymphoma(NKTCL), nasal type, occurring primarily in the prostate gland, is extremely rare. We present a case of primarily prostatic NKTCL in a 59-year-old man suffering from dysuria. Histological examinations revealed that diffused, large-sized, pleomorphic lymphocytes were arranged in an angiocentric distribution with large areas of geographic necroses. Additionally, the prostatic glands were diffusely infiltrated by heteromorphous lymphocytes forming lymphoepithelial lesions. The tumor cells were strongly expressed CD3ϵ, CD56, TIA-1, granzyme B and EBV-encoded RNAs. And interestingly, the lymphoid cells were also strongly immunoreactive with CD30. A rearrangement study showed T-cell receptor γ-chain gene rearrangement with monoclonal appearance. Though postoperative combination of chemotherapy was given, the patient died four months later. Our observation and other literatures indicate that extremely rare NKTCLs unusually express CD30. TCR gene rearrangement existed in some NKTCL, suggesting that a subset of NKTCL may be a mixed NK/T-cell differentiation. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9671878568932824.


Assuntos
Linfoma Extranodal de Células T-NK/genética , Neoplasias da Próstata/genética , Biomarcadores Tumorais/genética , Infecções por Vírus Epstein-Barr/complicações , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/fisiologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Antígeno Ki-1/metabolismo , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/virologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/virologia , Receptores de Antígenos de Linfócitos T/genética
14.
Zhonghua Nan Ke Xue ; 19(9): 794-7, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24386856

RESUMO

OBJECTIVE: To investigate the impact of cigarette smoking on sperm nucleoprotein transition and its association with sperm motility in infertile males. METHODS: We examined the semen quality and sperm nucleoprotein transition of 116 non-smokers and 113 heavy smokers (aged 25 -50 years) who visited the Research Institute of Obstetrics and Gynecology for male infertility. We determined the rate of individual sperm nucleoprotein transition by aniline blue staining and analyzed the correlation of cigarette smoking with routine semen parameters and the rate of sperm nucleoprotein transition. Based on the smoking index (SI) derived from smoking frequency (no. of cigarettes/d) multiplied by smoking duration (yr), the men with SI = 0 were considered as non-smokers, and those with SI > or = 200 as heavy smokers. RESULTS: The rate of abnormal sperm nucleoprotein transition was significantly higher in the asthenozoospermic (23.5 +/- 9.4, P < 0.01) and oligoasthenozoospermic (28.2 +/- 9.2, P < 0.01) than in the normozoospermic males (19.0 +/- 9.0). Compared with the non-smokers, cigarette smoking remarkably reduced sperm nucleoprotein transition in both the men with normal sperm motility (21.9 +/- 9.8 vs 16.8 +/- 7.7, P < 0.01) and those with abnormal sperm motility (26.0 +/- 9.9 vs 22.7 +/- 8.8, P < 0.05). A weak correlation was observed between the rate of sperm nucleoprotein transition and routine semen parameters. CONCLUSION: Cigarette smoking is not significantly correlated with sperm motility but decreases sperm nucleoprotein transition in infertile males.


Assuntos
Infertilidade Masculina/metabolismo , Nucleoproteínas/metabolismo , Fumar/efeitos adversos , Espermatozoides/patologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Motilidade Espermática/efeitos dos fármacos
15.
Zhonghua Nan Ke Xue ; 19(12): 1111-4, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24432625

RESUMO

OBJECTIVE: To investigate the diagnosis and treatment of male Kallmann syndrome. METHODS: We retrospectively analyzed the clinical data of 12 cases of male Kallmann syndrome, 3 treated for male sterility and the other 9 for secondary sex characteristics dysplasia and external genitalia developmental anomalies, all by combined replacement therapy with human chorionic gonadotropin (hCG), human menopause gonadotropin (hMG) and testosterone undecanoate for 6 months to 3 years. We compared the secondary sexual development and serum sex hormone levels of the patients before and after treatment. RESULTS: After 9 months of treatment, all the 12 patients showed significant improvement in the penile length, testicular volume and sex hormone levels (P < 0.01), with different degrees of promotion of the secondary sexual development. Three married cases could have normal sexual intercourse, and one of them achieved normal pregnancy. CONCLUSION: The clinical characteristics of Kallmann syndrome include lack of gonadotropins, lower gonad function and loss or reduction of olfactory sensation. Replacement therapy with hCG, hMG and androgens is an effective treatment method. However, no effective therapy is now available for olfactory dysfunction. Early diagnosis and hormone replacement therapy can best alleviate its clinical symptoms and eventually achieve fertility.


Assuntos
Terapia de Reposição Hormonal , Síndrome de Kallmann/diagnóstico , Síndrome de Kallmann/tratamento farmacológico , Adolescente , Adulto , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
16.
Tohoku J Exp Med ; 228(3): 259-66, 2012 11.
Artigo em Inglês | MEDLINE | ID: mdl-23089668

RESUMO

Antioxidant genes and enzymes play important roles in human spermatogenesis. Although low levels of antioxidant enzyme expression are associated with poor sperm quality, it is not clear whether mRNA expression of antioxidant genes is lower in these men than in normozoospermic men. In this study, 55 asthenozoospermic and oligoasthenozoospermic patients and 65 controls were recruited. Quantitative real-time reverse transcription PCR was performed and the abundance of mRNA of four antioxidant genes known to be important to spermatogenesis were evaluated. These genes were nuclear factor erythroid 2-related factor 2 (NRF2), catalase (CAT), glutathione S-transferase Mu 1 (GSTM1), and superoxide dismutase isoenzyme 2 (SOD2). Results showed the level of NRF2 mRNA expression to be significantly lower in patients than in controls (P < 0.001), but no statistically significant difference in the level of SOD2, CAT, or GSTM1 gene expression was observed between the two groups. A significant correlation was observed between the level of NRF2 mRNA expression and specific sperm function parameters, including concentration, progressive motility, immotility, vitality, and morphology (all P < 0.01). NRF2 expression was also found to be associated with seminal SOD activity and mRNA levels of the CAT and SOD2 genes (all P < 0.05). Therefore, our data demonstrated that the level of NRF2 mRNA expression is significantly lower in human males with low sperm motility and correlated with specific sperm function parameters. This suggests that NRF2 is important to spermatogenesis and may serve as a useful biomarker in the prediction of male infertility.


Assuntos
Astenozoospermia/genética , Fator 2 Relacionado a NF-E2/genética , Espermatozoides/metabolismo , Adulto , Astenozoospermia/diagnóstico , Astenozoospermia/metabolismo , Biomarcadores/análise , Biomarcadores/metabolismo , Estudos de Casos e Controles , Regulação para Baixo/genética , Expressão Gênica , Humanos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Masculino , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/metabolismo , Prognóstico , RNA Mensageiro/metabolismo , Análise do Sêmen/métodos , Motilidade Espermática/genética , Espermatogênese/genética
17.
Asian Pac J Cancer Prev ; 13(6): 2635-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22938433

RESUMO

BACKGROUND: Many studies have investigated the association between glutathione S-transferase T 1 (GSTT1) null genotype and risk of prostate cancer, but the impact of GSTT1 null genotype in Asians is still unclear owing to inconsistencies across results. Thie present meta-analysis aimed to quantify the strength of the association between GSTT1 null genotype and risk of prostate cancer. METHODS: We searched the PubMed, Embase and Wangfang databases for studies of associations between the GSTT1 null genotype and risk of prostate cancer in Asians and estimated summary odds ratio (OR) with their 95% confidence interval (95% CI). RESULTS: A total of 11 case-control studies with 3,118 subjects were included in this meta-analysis, which showed the GSTT1 null genotype to be significantly associated with increased risk of prostate cancer in Asians (random-effects OR = 1.49, 95% CI 1.15-1.92, P = 0.002), also after adjustment for heterogeneity (fixed-effects OR = 1.45, 95% CI 1.23-1.70, P< 0.001). No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis of available data suggested the GSTT1 null genotype does contribute to increased risk of prostate cancer in Asians.


Assuntos
Predisposição Genética para Doença , Glutationa Transferase/genética , Neoplasias da Próstata/genética , Ásia , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Genótipo , Glutationa Transferase/deficiência , Humanos , Masculino , Fatores de Risco
18.
J Mol Med (Berl) ; 90(11): 1333-42, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22648520

RESUMO

Defective spermatogenesis, which severely impairs male fertility, can be caused by excessive reactive oxygen species (ROS). Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates transcription of genes encoding enzymes important for protection against ROS. In human seminal plasma and spermatozoa, superoxide dismutase isoenzymes (SOD) and glutathione S-transferases (GST) are key antioxidant enzymes. We hypothesized that decreased function of the Nrf2-antioxidant response element (ARE) pathway might predispose individuals to male infertility. In this study, we identified three functional single nucleotide polymorphisms (SNPs) in the Nrf2 promoter regions of 196 idiopathic asthenozoospermic patients, 140 idiopathic oligoasthenozoospermic patients, and 295 controls. We found that two of the Nrf2 SNPs (-617 G > T and -653 T > C) were associated with oligoasthenozoospermia (p = 0.001) and individuals with 617 TT and 653 TT genotypes had higher risk of oligoasthenozoospermia (p = 0.006 and p = 0.002). Four haplotypes of Nrf2 promoters were identified, and two of them (GCC and TCT) had different frequencies in oligoasthenozoospermic patients than in controls (p = 0.019 and p = 0.011). In vitro reporter assay indicated that oligoasthenozoospermia associated genotypes of Nrf2 had significantly decreased transcriptional capabilities. The GCC and TCT haplotypes both showed lower Nrf2 mRNA expression in spermatozoa than GCT. TCT also showed decreased levels of antioxidant gene GSTM1 and SOD2 mRNA. Analysis of total seminal SOD activity elucidated that oligoasthenozoospermic patients had less SOD activity than controls. This study is the first to demonstrate a strong association between functional polymorphisms in Nrf2 promoters with defective spermatogenesis in humans.


Assuntos
Variação Genética , Infertilidade Masculina/genética , Fator 2 Relacionado a NF-E2/genética , Espermatogênese/genética , Adulto , Astenozoospermia/genética , Genes Reporter , Genótipo , Glutationa Transferase/metabolismo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polimorfismo de Nucleotídeo Único , Espécies Reativas de Oxigênio , Risco , Fumar , Superóxido Dismutase/metabolismo
19.
Zhonghua Nan Ke Xue ; 18(1): 67-9, 2012 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-22295853

RESUMO

OBJECTIVE: To explore the correlation of the testosterone level with circulated endothelial progenitor cells in patients with Klinefelter's syndrome (KS) and its clinical significance. METHODS: This study included 36 patients affected by non-mosaic 47, XXY KS, each with one or more cardiovascular risk factors. Serum hormone levels and the content of circulated endothelial progenitor cells were determined by radioimmunology and cell culture methods, respectively, and the measurement was repeated after 6 months of testosterone replacement therapy. RESULTS: After testosterone replacement therapy, the testosterone level was increased from (8 +/- 3) to (24 +/- 10) nmol/L, while the content of endothelial progenitor cells ([41 +/- 48] cells/ml) showed no significant rise. CONCLUSION: There is no obvious correlation between the testosterone level and the content of endothelial progenitor cells in KS patients.


Assuntos
Células Endoteliais/citologia , Síndrome de Klinefelter/sangue , Células-Tronco/citologia , Testosterona/sangue , Adulto , Contagem de Células , Terapia de Reposição Hormonal , Humanos , Infertilidade Masculina/sangue , Síndrome de Klinefelter/tratamento farmacológico , Masculino , Testosterona/uso terapêutico
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