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This study aims to identify potential efficacy-related biomarkers and investigate the mechanism of Youjing granule (YG) in improving spermatogenic function in rats based on metabolomics combined with network pharmacology. We obtained YG-containing serum from Sprague-Dawley rats, compared it with control group serum and analyzed it using gas chromatography-mass spectroscopy to identify potential biomarkers and investigate the mechanism of YG in improving spermatogenic function in rats. Six important differential biomarkers, comprising putrescine, amidine, arginine, d-fructose-6-phosphate, l-proline and galactose, were identified in the YG-containing serum and then used to explore the potential mechanisms. The ultra-high-performance liquid chromatography-high-resolution mass spectrometry technology was adopted for the rapid separation, identification and analysis of chemical components of YG in blood. A total of 69 detected chromatographic peaks were revealed. The binding energy between core compounds and key proteins is low, among which dipsacoside B is the best. The outcomes suggest that YG may improve spermatogenic function in rats by facilitating the development of spermatogonial stem cells, counteracting oxidative stress and controlling cellular apoptosis. Youjing granule may also affect the energy required for sperm production or influence sperm growth and maturation.
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RATIONALE: Male infertility is a common reproductive system disease manifested as aberrant spermatogenesis and identified as "kidney deficiency and dampness" in Chinese traditional medicine. Youjing granule (YG) is a Chinese material medica based on tonifying kidneys and removing dampness. It has proven to be able to regulate semen quality in clinical application, but the underlying mechanism has not been clarified. METHODS: Using serum containing YG to treat primarily cultured spermatogonial stem cells (SSCs), the apoptotic rate and mitosis phase ratio of SSCs were measured. The liquid chromatography-tandem mass spectrometry with tandem mass tags method was applied for analyzing the serum of rats treated with YG/distilled water, and proteomic analyses were performed to clarify the mechanisms of YG. RESULTS: Totally, 111 proteins in YG-treated serum samples were differentially expressed compared with control groups, and 43 of them were identified as potential target proteins, which were further annotated based on their enrichment in Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Proteomic analyses showed that the mechanisms of YG may involve regulation of glycolysis, gluconeogenesis and nucleotide-binding and oligomerization domain-like receptor signaling pathway. In addition, RhoA and Lamp2 were found to be possible responders of YG through reviewing the literature. CONCLUSIONS: The results demonstrate that our serum proteomics platform is clinically useful in understanding the mechanisms of YG.
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Proteómica , Análisis de Semen , Ratas , Masculino , Animales , Proteómica/métodos , Proteínas/metabolismo , Espectrometría de Masas en Tándem , EspermatogénesisRESUMEN
As one of the common plasticizers, di-n-butyl phthalate (DBP) has been using in various daily consumer products worldwide. Since it is easily released from products and exists in the environment for a long time, it has a lasting impact on human health, especially male reproductive health. However, the detailed mechanism of testicular damage from DBP and the protection strategy are still not clear enough. In this study, we found that DBP could induce dose-dependent ferroptosis in testicular tissue. Mechanism dissection indicates that DBP can upregulate SP1 expression, which could directly transcriptionally upregulate PRDX6, a negative regulator of ferroptosis. Overexpression of PRDX6 or adding SP1 agonist curcumin could suppress the DBP-induced ferroptosis on testicular cells. In vivo, rats were given 500 mg/kg/day DBP orally for 3 weeks; elevated levels of ferroptosis were detected in testicular tissue. When the above-mentioned doses of DBP and curcumin at a dose of 300 mg/kg/day were administered intragastrically simultaneously, the testicular ferroptosis induced by DBP was alleviated. Immunohistochemistry and quantitative real-time PCR of testis tissue showed that the expression of PRDX6 was upregulated under the action of DBP and curcumin. These findings suggest a spontaneous self-protection mechanism of testicular tissue from DBP damage by upregulating SP1 and PRDX6. However, it is not strong enough to resist the DBP-induced ferroptosis. Curcumin can strengthen this self-protection mechanism and weaken the level of ferroptosis induced by DBP. This study may help us to develop a novel therapeutic option with curcumin to protect the testicular tissue from ferroptosis and function impairment by DBP.
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Curcumina , Ferroptosis , Ratas , Masculino , Humanos , Animales , Testículo , Dibutil Ftalato/toxicidad , Dibutil Ftalato/metabolismo , Curcumina/farmacología , Curcumina/metabolismo , Plastificantes/toxicidad , Plastificantes/metabolismo , Peroxiredoxina VI/genética , Peroxiredoxina VI/metabolismoRESUMEN
The performance and mechanisms of a titanium carbide (Ti3C2) MXene modified Fe3+/hydrogen peroxide (H2O2) system were compared in detail under dark and visible light conditions, with a new mechanism proposed for the reaction and reduction of MXene by Fe3+. Using Bisphenol A (BPA) as the target pollutant, the degradation of BPA by the Fe3+/H2O2 system was improved after adding MXene in the dark, and the degradation rate of BPA was ≥ 95 % within 12.5 min under visible light, six times higher than that in the dark. Fe2+ was ascertained to be the effective component responsible for H2O2 activation to produce ·OH. SEM, XPS, ICP, XRD, and FTIR spectroscopy, analyses show that MXene and Fe3+ form a complex, and then MXene reacts with Fe3+ by breaking the Ti-C bonding to accelerate the Fe3+/Fe2+ cycle. MXene uses photogenerated electrons to promote this reaction under visible light. In addition, quenching experiments and electron spin resonance spectroscopy results show that ·OH and O2â¢- are the main reactive oxygen species under visible light, while ·OH is the main active species in the dark. MXene thus effectively uses O2 to form O2â¢- under visible light and promotes the Fe3+/Fe2+ cycle. This study provides a theoretical basis for the combination of visible light catalysis and the advanced oxidation process of a Ti3C2 MXene.
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Male infertility has evolved from a common reproductive system disease to a major social issue. Youjing granule (YG) is a Chinese medicinal material used as a therapy method for tonifying the kidneys and removing dampness due to its pathogenic characteristics. YG has been shown to regulate sperm quality in clinical trials, but the underlying mechanism is not fully understood. The present study was aimed to explore the protective effects and mechanism of action of YG on male reproductive system damage caused by methyl methane sulfonate (MMS). We first established an infertility model of rats through oral administration of MMS and then treated with YG. To determine the effect of YG, spermatogenesis, microvascular density, and secretory function of Leydig cells and Sertoli cells in rats were assessed. Spermatogonial stem cells (SSCs) were co-cultured with mouse embryo fibroblast (MEF) cells as an in vitro cell model before exposure to serum containing YG. Furthermore, the proliferation and apoptosis of SSCs were measured. Results indicated that YG increased the expression of self-renewal and proliferation-related molecules such as glial cell line derived neurotrophic factor (GDNF) and fibroblast growth factor-2 (FGF2), and improved the quality of sperm and the proliferation of SSCs. In conclusion, YG may protect spermatogenetic function of rats through regulating the proliferation and self-renewal of SSCs.
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Espermatogonias , Células Madre , Animales , Proliferación Celular , Masculino , Ratones , Ratas , Semen , EspermatogénesisRESUMEN
OBJECTIVE: This study is set out to explore the potential difference of miR in PD through GEO data and provide diagnostic indicators for clinical practice. METHODS: In this study, differential miR was screened through the Gene Expression Omnibus (GEO) database, 68 PD patients treated in our hospital from May 2017 to March 2018 were collected as the research group (RG), and 50 normal subjects who underwent physical examination in our hospital during the same period were collected as the control group (CG). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression and diagnostic value of miR-374a-5p in serum of patients. The potential target genes of miR-374a-5p were predicted, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology Consortium (GO) were carried out. RESULTS: GEO2R analysis revealed that 193 miRs are expressed differentially, of which 78 were highly expressed and 115 were poorly expressed. The miR-374a-5p expression in the serum of the RG was reduced markedly and had a diagnostic value. Targetscan and miRDB online websites were used to predict their target genes, with 415 common target genes. miR-374a-5p may participate in 27 functional pathways and 8 signal pathways. CONCLUSION: miR-335-5p has low expression in PD and is expected to be a potential diagnostic indicator.
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MicroARNs/genética , Enfermedad de Parkinson/genética , Estudios de Casos y Controles , Biología Computacional , Bases de Datos de Ácidos Nucleicos , Ontología de Genes , Marcadores Genéticos , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/estadística & datos numéricos , Enfermedad de Parkinson/diagnóstico , Transducción de Señal/genéticaRESUMEN
Interface engineering has been regarded as an effective strategy to improve thermoelectric (TE) performance by modulating electrical transport and enhancing phonon scattering. Herein, we develop a new interface engineering strategy in SnTe-based TE materials. We first use a one-step solvothermal method to synthesize SnTe powders decorated by Sb2Te3 nanoplates. After subsequent spark plasma sintering, we found that an ion-exchange reaction between the Sb2Te3 and SnTe matrixes happens to result in Sb doping and the formation of SnSb nanoparticles and the recrystallization of the nanograined SnTe at the grain boundaries of the SnTe matrix. Benefitting from this unique engineering, a significantly reduced lattice thermal conductivity of â¼0.64 W m-1 K-1 and a high zT of â¼1.08 (â¼100% enhanced) at 873 K are achieved in SnTe-Sb0.06. Such improved TE properties are attributed to the optimized carrier concentration and valence band convergence due to the Sb doping and enhanced phonon scattering by interface engineering at the grain boundaries. This work has demonstrated a facile and effective method to realize high-TE-performance SnTe via interface engineering.
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OBJECTIVE: The purpose of the study was to evaluate the effect of family-centered nursing based on Timing It Right Framework (TIR) on self-management and quality of life in patients with acute cerebral infarction. METHODS: According to the rules of randomized control, 100 patients with acute cerebral infarction were divided into two groups, including the control group (n=50) received treatment of routine nursing and follow-up, and the research group (n=50) implemented with a family-centered nursing based on TIR. The changes in self-management ability, mental function, social function, psychological resilience, quality of life, and family nursing ability at discharge and 6 months after discharge were compared between the two groups, and the data of patients' adherence to medication and nursing satisfaction were collected. RESULTS: The overall excellent rate of medication adherence and nursing satisfaction in the research group (96.00%, 98.00%) were significantly higher than those in the control group (80.00%, 78.00%) (P<0.05). The scores of ESCA, CD-RISC, and GQOL-74 in the research group were significantly higher than those in the control group after discharge, while the scores of SDSS, FCTI and NIHSS in the research group were significantly lower than those in the control group (P<0.05). CONCLUSION: The implementation of the family-centered nursing based on TIR can promote the self-management ability and quality of life, improve psychological resilience, enhance social function and family nursing ability, and improve medication adherence and the nurse-patient relationship in patients with acute cerebral infarction.
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CD9 is a trans-membrane protein, and has recently been implicated in different physiological and cellular processes, such as cell migration and adhesion. According to previous study, down-regulation of CD9 contributes to keratinocyte migration, critical for wound re-epithelialization. Nevertheless, it is widely believed that tetraspanin CD9 does not have ligands or function as the cell surface receptor, rather it is thought to associate with other transmembrane molecules, thereby mediate keratinocyte migration. Little is known about how CD9 associates with transmembrane molecules in migratory keratinocytes. Here, using confocal microscopy, we observed that tetraspanin CD9 and ADAM17 co-localized on the surface of keratinocytes in the course of wound repair in vivo and in vitro. Co-immunoprecipitation experiments demonstrated a direct association between CD9 and ADAM17 in HaCaT cells and C57-MKs. Functional studies revealed that down-regulation or over-expression of CD9 exerted negative regulatory effects on ADAM17 sheddase activity. This activity is involved in CD9-regulated cell motility and migration. Further studies found that ADAM17 inhibitor-TAPI-2 or siADAM17 significantly abolished the enhanced effect of keratinocyte migration induced by CD9 down-regulation. Meanwhile, the sheddase activity of ADAM17 was inhibited by TAPI-2, which decreased this release of AREG and HB-EGF in CD9-silenced HaCat cells and C57-MKs. Importantly, neutralizing antibody against HB-EGF significant weakened keratinocyte migration and motility in CD9-silenced keratinocytes, and the inhibition of CD9-regulated keratinocyte migration by siADAM17 was rescued by addition of recombinant HB-EGF, activating EGFR/ERK pathway. Collectively, our results suggest that ADAM17 sheddase activity is activated by down-regulation of CD9, thereby mediating shedding of HB-EGF and activation of EGFR/ERK signaling, which crucially affects the keratinocyte migration and wound healing.
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Proteína ADAM17/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Tetraspanina 29/metabolismo , Proteína ADAM17/genética , Western Blotting , Línea Celular , Movimiento Celular/genética , Movimiento Celular/fisiología , Células Cultivadas , Humanos , Inmunohistoquímica , Inmunoprecipitación , Transducción de Señal/genética , Transducción de Señal/fisiología , Tetraspanina 29/genética , Cicatrización de Heridas/genética , Cicatrización de Heridas/fisiologíaRESUMEN
Di-N-butylphthalate (DBP) is one of the most common endocrine-disrupting chemicals which can disrupt human endocrine system, especially in the male reproductive system. Here, this study was aimed to determine whether sulforaphane (SFN) could protect against testicular oxidative stress injury induced by DBP in male mice offsprings. Wild-type (Nrf2+/+) and Nrf2-deficient (Nrf2-/-) timed-pregnant mice were given DBP orally from embryonic day (E)14.5 to E19.5. Subsequently, the oxidative stress markers were evaluated. Besides, Nrf2, NF-κB, I-kB, HO-1 and NQO-1 expression levels in the testis were measured by immunohistochemical staining or western blot analysis. DBP significantly reduced anogenital distance (AGD) and influenced testes growth in male mice offsprings, while SFN ameliorated these phenotypes. After DBP stimulation, the testicular morphology, testicular cell apoptosis index and the oxidative stress markers exhibited statistical differences compared with Control group, while SFN supplementation showed obvious improvements. In addition, administration of SFN could obviously increase the expression level of Nrf2 and its downstream ARE gene battery, such as HO-1, NQO-1 in the testis. Meanwhile, SFN pretreatment did not confer protection against DBP-induced testicular oxidative stress injury in Nrf2 knockout mice. Therefore, the present findings suggested that SFN could effectively protect against DBP-induced testicular oxidative stress injury through Nrf2/ARE signaling pathways in male mice offsprings.
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Previous studies have investigated the relationships between PSCA rs2294008 C>T and rs2976392 G>A polymorphisms and cancer susceptibility. However, the available findings remained inconsistent and even controversial. Thus, the aim of this meta-analysis was performed to clarify such associations. The online databases PubMed, EMBASE and Web of Science searched for relevant studies, covering all the papers published until September 1st, 2016. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of such associations. Then, trial sequential analysis was performed to estimate whether the evidence of the results was firm. Overall, a significant increased risk of cancer was associated with PSCA rs2294008 C>T and rs2976392 G>A polymorphisms. For the PSCA rs2294008 polymorphism, when stratified by type of cancer, the results were significant especially in gastric cancer and bladder cancer. Moreover, in the subgroup analysis by ethnicity, significant results were detected in both Asian and Caucasian populations. Similarly, for the PSCA rs2976392 polymorphism, the stratification analyses by type of cancer showed that the results were significant only in gastric cancer. In addition, the stratification analyses by ethnicity detected that this polymorphism increased cancer risk only in Asian populations. Then, trial sequential analyses demonstrated that the results of the meta-analysis were based on sufficient evidence. Therefore, this meta-analysis suggested that the PSCA rs2294008 C>T and rs2976392 G>A polymorphisms might be associated with cancer susceptibility, which might act as a potential predicted biomarker for genetic susceptibility to cancer, especially in gastric cancer and bladd er cancer.
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BACKGROUND: To evaluate the role of free-hand transperineal targeted prostate biopsy using multiparametric magnetic resonance imaging-transrectal ultrasound (mpMRI-TRUS) fusion in Chinese men with repeated biopsy. METHODS: A total of 101 consecutive patients suspicious of prostate cancer (PCa) at the mpMRI scan and with prior negative biopsy and elevated PSA values were prospectively recruited at two urological centers. Suspicious areas on mpMRI were defined and graded using PI-RADS score. Targeted biopsies (TB) were performed for each suspicious lesion and followed a 12-core systematic biopsy (SB). Results of biopsy pathology and whole-gland pathology at prostatectomy were analyzed and compared between TB and SB. The risk for biopsy positivity was assessed by univariate and multivariate logistic regression analysis. RESULTS: Fusion biopsy revealed PCa in 41 of 101 men (40.6%) and 25 (24.8%) were clinically significant. There was exact agreement between TB and SB in 74 (73.3%) men. TB diagnosed 36% more significant cancer than SB (22 vs 13 cases, P = 0.012). When TB were combined with SB, an additional 14 cases (34.1%) of mostly significant PCa (71.4%) were diagnosed (P = 0.036). TB had greater sensitivity and accuracy for significant cancer than SB in 26 men with whole-gland pathology after prostatectomy. PI-RADS score on mpMRI was the most powerful predictor of PCa and significant cancer. CONCLUSIONS: Free-hand transperineal TB guided with MRI-TRUS fusion imaging improves detection of clinical significant PCa in Chinese men with previously negative biopsy. PI-RADS score is a reliable predictor of PCa and significant cancer.
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Imagen por Resonancia Magnética , Próstata/patología , Neoplasias de la Próstata/patología , Ultrasonografía Intervencional , Anciano , Humanos , Hidroxietilrutósido , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Imagen Multimodal/métodos , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/diagnóstico por imagen , RectoRESUMEN
di-N-butylphthalate (DBP) is a ubiquitous environmental pollutant used for plastic coating and in the cosmetics industry. It has toxic effects on body health, especially the male reproductive system. Here, we investigated the effects of DBP on the male reproductive system of pubertal mice and explored the protective role of sulforaphane (SFN). The results showed that DBP significantly reduced the anogenital distance, testicular weight, sperm count and motility, and plasma and testicular testosterone levels and significantly increased the oxidative stress, sperm abnormalities, and testicular cell apoptosis. SFN supplementation ameliorated these effects. After DBP stimulation, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1 and NQO1. Upregulation of Nrf2 by SFN reduced the DBP-mediated intracellular oxidative toxicity and also increased testosterone secretion and spermatogenesis, which were decreased by DBP. These findings indicate that SFN can attenuate DBP-induced reproductive damage in pubertal mice via Nrf2-associated pathways.
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Dibutil Ftalato/toxicidad , Contaminantes Ambientales/toxicidad , Isotiocianatos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Reproducción/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Masculino , Ratones , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Sulfóxidos , Testículo/citología , Testículo/efectos de los fármacos , Regulación hacia ArribaRESUMEN
Semen cryopreservation is widely used in assisted reproductive technologies, but it reduces sperm quality dramatically. The aim of this study was to develop a model using basal semen quality to predict the outcome of postthaw semen parameters and improve the efficiency of cryopreservation in a human sperm bank. Basal semen parameters of 180 samples were evaluated in the first stage, and a multiple logistic regression analysis involving a backward elimination selection procedure was applied to select independent predictors. After a comprehensive analysis of all results, we developed a new model to assess the freezability of sperm. Progressive motility (PR), straight-line velocity (VSL) and average path velocity (VAP) were included in our model. A greater area under the receiver operating characteristic curve was obtained in our model when compared with other indicators. In the second stage of our study, samples that satisfied the new model were selected to undergo freeze-thawing. Compared with the first stage, the rate of good freezability was increased significantly (94% vs 67%, P = 0.003). By determining basal semen quality, we have developed a new model to improve the efficiency of cryopreservation in a human sperm bank.
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Criopreservación/métodos , Preservación de Semen/métodos , Bancos de Esperma/métodos , Adulto , Congelación , Humanos , Masculino , Modelos Estadísticos , Análisis Multivariante , Pronóstico , Curva ROC , Análisis de Semen , Espermatozoides , Adulto JovenRESUMEN
OBJECTIVES: To prospectively compare biopsy outcomes between free-hand transperineal mpMRI/TRUS fusion targeted biopsy (TB) and transperineal systematic biopsy (SB) in patients with first prostate biopsy. PATIENTS AND METHODS: In all, 224 consecutive patients with the suspicion of PCa were investigated. All patients were evaluated by 3.0-T mpMRI applying the ESUR criteria. All patients underwent free-hand transperineal mpMRI/TRUS fusion TB and additionally a transperineal SB. Pathological findings of TB, SB, and step-sectioned RP specimens were analyzed. RESULTS: The median age of the patients was 69 (40-85) years, median PSA level was 10.05 (3.61-78.39) ng/mL, and median prostate volume was 45.5 (22-77) mL. Overall, the PCa detection rate was 50.45% (113/224). TB detected significantly more cancer [44.2% (99/224) vs. 34.8% (78/224); P = 0.001] and clinically significant PCa [75.75% (75/99) vs. 62.82% (49/78); P = 0.005] than SB. For the upgrading of Gleason score, 39.74% (31/78), more clinically significant PCa was detected by using additional TB than by SB alone. Conversely, 5.05% (5/99) more clinically significant PCa was found by SB in addition to that by TB. The location of 96.67% (58/60) and Gleason score of 60% (36/60) of TB-proven ITs were correctly identified, as corroborated by RP specimens. The median IT volume was 1.125 (0.21-19.87) ml on MRI and 1.41 (0.13-9.56) ml in RP specimens. CONCLUSIONS: Free-hand transperineal mpMRI/TRUS fusion biopsy was associated with a higher detection rate of clinically significant PCa while taking fewer cores. Moreover, this technique can reliably predict the location, and relatively reliably predict cancer volume and Gleason score of ITs.
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Biopsia Guiada por Imagen/métodos , Próstata/patología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , China , Imagen de Difusión por Resonancia Magnética/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética Intervencional , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tamaño de los Órganos , Peritoneo , Estudios Prospectivos , Antígeno Prostático Específico/sangre , RectoRESUMEN
Acute kidney injury (AKI) induced by ischemia-reperfusion is a critical conundrum in many clinical settings. Here, this study aimed to determine whether and how RTA-408, a novel oleanane triterpenoid, could confer protection against renal ischemia-reperfusion injury (IRI) in male mice. Mice treated with RTA-408 undergoing unilateral ischemia followed by contralateral nephrectomy had improved renal function and histological outcome, as well as decreased apoptosis, ROS production, and oxidative injury marker compared with vehicle-treated mice. Also, we had found that RTA-408 could strengthen the total antioxidant capacity by increasing Nrf2 nuclear translocation and subsequently increased Nrf2 downstream GSH-related antioxidant gene expression and activity. In vitro study demonstrated that GSH biosynthesis enzyme GCLc could be an important target of RTA-408. Furthermore, Nrf2-deficient mice treated with RTA-408 had no significant improvement in renal function, histology, ROS production, and GSH-related gene expression. Thus, by upregulating Nrf2 and its downstream antioxidant genes, RTA-408 presents a novel and potential approach to renal IRI prevention and therapy.
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Glutatión/biosíntesis , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Daño por Reperfusión/prevención & control , Triterpenos/farmacología , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Glutatión/genética , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Regulación hacia ArribaRESUMEN
BACKGROUND: Some previous studies have investigated the relationship between insulin-like growth factor-binding protein-3 polymorphism and prostate cancer (PCa) susceptibility; however, the findings from those studies remain inconsistent. Hence, the aim of this meta-analysis was to provide a more reliable conclusion about such associations. METHODS: A meta-analysis based on twelve studies was conducted, and 8,341 PCa cases and 7,734 controls were included in this analysis. All relevant studies published till February 1, 2016, were identified by searching the databases such as PubMed, EMBASE, and Web of Science. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) in order to assess the strength of such associations. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. RESULTS: Several articles provided data only for particular genotypes; therefore, only dominant model analyses were carried out for all of these studies. Initially, the results from this analysis indicated that rs2854744 was not associated with PCa susceptibility (OR=1.12, 95% CI=0.996-1.2). However, after excluding one study due to its heterogeneity and publication bias, a significant relationship was detected between rs2854744 and PCa risk (OR=1.10, 95% CI=1.03-1.17). When stratified by genotyping method, significant results were detected only in the Sequenom method group (OR=1.13, 95% CI=1.04-1.22). Moreover, the results from a subgroup analysis that was conducted by using source of controls were significant only in the population-based control group. CONCLUSION: This meta-analysis suggested that the insulin-like growth factor-binding protein-3 polymorphism-202 A/C was associated with PCa susceptibility.
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The aim of the present study was to determine whether magnetic resonance imaging - ultrasound (MRI-US) fusion prostate biopsy is superior to systematic biopsy for making a definitive diagnosis of prostate cancer. The two strategies were also compared regarding their ability to detect clinically significant and insignificant prostate cancer. A literature search was conducted through the PubMed, EMBASE and China National Knowledge Infrastructure databases using appropriate search terms. A total of 3,415 cases from 21 studies were included in the present meta-analysis. Data were expressed as relative risk (RR) and 95% confidence interval. The results revealed that MRI-US fusion biopsy achieved a higher rate of overall prostate cancer detection compared with systematic biopsy (RR=1.09; P=0.047). Moreover, MRI-US fusion biopsy detected more clinically significant cancers compared with systematic biopsy (RR=1.22; P<0.01). It is therefore recommended that multi-parametric MRI-US is performed in men suspected of having prostate cancer to optimize the detection of clinically significant disease, while reducing the burden of biopsies.
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Gastric cancer is one of the leading causes of cancer death worldwide. However, precise molecular mechanisms underlining its development are far from clear. We recently reported that PES1 promoted development of breast cancer and ovarian cancer as an oncogene. In this study, we reported that ablation of endogenous PES1 resulted in significant suppression of cell proliferation and growth and led to cell cycle arrest in G2 or G1 phase, respectively, in two gastric cancer cell lines (AGS and N87) in vitro. Meanwhile, silencing of PES1 obviously decreased expressions of cyclin D1, HIF-1α, and vascular endothelial growth factor (VEGF) expressions and increased p21WAF1 expression. Re-expression of PES1 in these two kinds of PES1 knockdown cells rescued these effects. In vivo, repression of endogenous PES1 expression suppressed gastric tumor growth in nude mice. In addition, 40.7 % (24/59) of gastric cancer tissues showed PES1 expression via immunohistochemical (IHC) staining. However, there were not any positive PES1 stainings in matched adjacent tissues. Our results demonstrated that repression of PES1 changed expressions of some cell proliferation- and angiogenesis-related genes and inhibited gastric cancer growth, and PES1 expression increased in gastric cancer tissues. These results suggest that PES1 may play an important role in development of gastric cancer. PES1 may be a potential target for gastric cancer therapy.
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Proteínas/fisiología , Neoplasias Gástricas/patología , Animales , Línea Celular Tumoral , Proliferación Celular , Humanos , Ratones , Ratones Endogámicos BALB C , Proteínas/análisis , Proteínas de Unión al ARN , Neoplasias Gástricas/irrigación sanguínea , Neoplasias Gástricas/etiologíaRESUMEN
Sperm cryopreservation is a method to preserve sperm samples for a long period. However, the fertility of sperm decreases markedly after freezing and thawing in a certain amount of samples. The aim of the present study was to find useful and reliable predictive biomarkers of the capacity to withstand the freeze-thawing process in human ejaculates. Previous researches have shown that enolase1 (ENO1) and glucose-6-phosphate isomerase (GPI) are closely related to spermatozoa quality. We chose the two proteins as probable markers of sperm freezing capacity. Ejaculate samples were separated into good freezability ejaculates (GFE) and poor freezability ejaculates (PFE) according to progressive motility of the sperm after thawing. Before starting cryopreservation protocols, the two proteins from each group were compared using western blot analysis and immunofluorescence. Results showed that normalized content of ENO1 (P<0.05) and GPI (P<0.01) were both significantly higher in GFE than in PFE. The association of ENO1 and GPI with postthaw sperm viability and motility was confirmed using Pearson's linear correlation. In conclusion, ENO1 and GPI can be used as markers of human sperm freezability before starting the cryopreservation procedure.