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1.
World J Urol ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965289

RESUMO

OBJECTIVE: Inflammation plays an important role in the development of benign prostatic hyperplasia (BPH). The aim of the present study was to reference the study of the pathological changes in the prostate gland of rats with experimental autoimmune prostatitis (EAP), for the development of experimental models of BPH. METHODS: Experimental autoimmune prostatitis was induced in rats by the intradermal injection of rat prostate antigen with immunoadjuvants. In case of the positive BPH group, BPH was induced by the subcutaneous injection of testosterone propionate. At the end of the 45-day model period, prostate weights were measured, and the histopathological analysis of the prostate glands was performed. The levels of cytokines, TGF-ß1/RhoA/ROCK signals, and the oxidative stress status were also examined. RESULTS: Rats from the EAP group had a higher histological score than those from the control group. Compared to the samples from rats in the hormone-induced group, those from the EAP group showed a more pronounced increase in the size of the stromal compartment; this was characterized by the formation of reactive stroma and the deposition of a greater amount of extracellular matrix (ECM). Significant increases in the numbers of CD3-positive cells and CD68-positive cells, as well as a significant upregulation in the cytokine levels, and an increase in the TGF-ß1 levels and activation of RhoA/ROCK signaling, were observed in the samples from rats in the EAP group. CONCLUSION: Chronic inflammation can induce BPH in rats via EAP model method. When performing drug experiments on the stroma compartments of BPH, the use of the EAP model is a recommendation of the authors based on this study.

2.
J Hazard Mater ; 390: 122160, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31999958

RESUMO

An oxygen-constrained system of crude oil reservoir environment was constructed to stimulate the growth of indigenous microbes, such as petroleum hydrocarbon-degrading bacteria. Addition of nitrogen and phosphorus sources was investigated for the growth of petroleum hydrocarbon-degrading bacteria. The results show that nitrates and phosphates stimulated the growth of the bacteria and promoted the biodegradation of crude oil as the sole carbon source in this process. The minimum surface tension was 29.63 mN/m when the amounts of the nitrogen (NaNO3: [Formula: see text]  = 2:1) and phosphorus (KH2PO4: NaH2PO4 = 5:2) sources added were 0.8 wt% and 1.4 wt%, respectively. Furthermore, the dominant petroleum hydrocarbon-degrading bacteria were shifted from Arcobacter in production water to Pseudomonas after the first subculture and then to Bacillus after the sixth subculture. The heteroatom groups in the crude oil were biodegraded simultaneously with normal alkanes and alkyl cyclohexanes. Addition of the nutrients resulted in microbial growth, microbial community shift, and enhanced microbial degradation.

3.
Behav Brain Res ; 379: 112375, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31759046

RESUMO

Physical exercise is well-established paradigm for improving adult neurogenesis and brain functions. As considered as an alternative therapeutic strategy, treadmill running could reduce cognitive impairment and psychiatric abnormalities associating post-traumatic stress disorder (PTSD), which might associate with the promote effects to adult neurogenesis. In current study, we aimed to address how treadmill exercise benefit adult hippocampal neurogenesis in PTSD model and the underlying molecular mechanism related with Akt signaling. PTSD was induced by exposure to aggressor and treatments were conducted with different intensity of compulsory treadmill running. We observed treadmill running improved hippocampal neurogenesis including proliferation and neural differentiation of neural stem cells (NSCs). Moreover, behavioral tests showed treadmill could attenuate the cognitive deficit and depressive/anxiety like behaviors in correlating with PTSD model. Moreover, treadmill running recovered the Akt activity in hippocampus. Interrupting treadmill running administrated mice with Akt inhibitor GSK690693 resulted in the blocked the effects of treadmill running to hippocampal neurogenesis and behavioral improvement in PTSD mice model. In conclusion, treadmill running could mediate behavioral functions and improve hippocampal neurogenesis in PTSD model by regulating Akt signaling.

4.
Cancer Manag Res ; 11: 9921-9930, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819630

RESUMO

Purpose: The imaging features of patients with early-stage non-small cell lung cancer (NSCLC) receiving stereotactic body radiotherapy (SBRT) are crucial for the decision-making process to establish a treatment plan. The purpose of this study was to predict the clinical outcomes of SBRT from the textural features of pretreatment computed tomography (CT) images. Patients and methods: Forty-one early-stage NSCLC patients who received SBRT were included in this retrospective study. In total, 72 textural features were extracted from the pretreatment contrast-enhanced CT images. Survival analysis was used to identify high-risk groups for progression-free survival (PFS) and disease-specific survival (DSS). Receiver operating characteristic (ROC) curve analysis was utilized to estimate the diagnostic abilities of the textural parameters. Univariable and multivariable Cox regression analyses were performed to evaluate the predictors of PFS and DSS. Results: Four parameters, including entropy (P=0.003), second angular moment (SAM) (P=0.04), high-intensity long-run emphasis (HILRE) (P=0.046) and long-run emphasis (LRE) (P=0.042), were significant prognostic features for PFS. In addition, contrast (P=0.008), coarseness (P=0.017), low-intensity zone emphasis (LIZE) (P=0.01) and large number emphasis (LNE) (P=0.046) were significant prognostic factors for DSS. In the ROC analysis, the area under the curve (AUC) of coarseness for local recurrence (LR) was 0.722 (0.528-0.916), and the AUC of entropy for lymph node metastasis (LNM) was 0.771 (0.556-0.987). The four highest AUCs for distant metastasis (DM) were 0.885 (0.784-0.985) for LNE, 0.846 (0.733-0.959) for SAM, 0.731 (0.500-0.961) for LRE and 0.731 (0.585-0.876) for contrast. In the multivariable analysis, smoking and entropy were independent prognostic factors for PFS. Conclusion: This exploratory study reveals that textual features derived from pretreatment CT scans have prognostic value in early-stage NSCLC patients treated with SBRT.

5.
Animals (Basel) ; 9(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752173

RESUMO

Natural plant extracts and probiotics has been proved as the most preferred and effective alternatives for antibiotics in animal feeding. The current study aimed to investigate the facilitating effect of tartary buckwheat flavonoids and Lactobacillus plantarum on the growth performance, nutrient digestibility, antioxidant capacity, and microbiota of weaned piglets. Fifty 35-day-old weaned piglets (7.85 ± 0.67 kg) were randomly divided into five treatments with 10 piglets per treatment. Piglets in the negative control (NC) group were fed a basal diet, and others were fed basal diets supplemented with 40 mg/kg of colistin sulfate (positive control, PC), 109 CFU/kg Lactobacillus plantarum (LP), 40 mg/kg of tartary buckwheat flavonoids (BF), and a combination of 109 CFU/kg Lactobacillus plantarum and 40 mg/kg of tartary buckwheat flavonoids (LB). Supplementation of BF increased the average daily gain of piglets in the BF group (p < 0.05). The nutrient digestibility of piglets in the NC group was lower than that in other groups, while the digestibility of gross energy, dry matter, organic matter, and phosphorus of piglets in the LB group was higher than the other four groups (p < 0.05). Compared with the NC and pC group, supplementation of Lp increased the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-px), and catalase (CAT), while the BF increased the content of IgA and IgM (p < 0.05). Supplementation of colistin sulfate decreased the alpha diversity index, including chao and observed species, while the addition of Lp or combination of Lp and BF increased the abundance of Selenomonas or Mitsuokella in fecal samples, respectively. The results indicated that supplementation of Lactobacillus plantarum can improve the antioxidant capacity, while tartary buckwheat flavones can increase the growth performance and immune ability of weaned piglets. Moreover, in combination, they promote nutrient digestibility.

6.
Sci Rep ; 9(1): 15772, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673044

RESUMO

Low permeability oil reservoirs are a widespread petroleum reservoir type all over the world. Therefore, methods to recover these reservoirs efficiently are of importance to guarantee energy supply. Here we report our novel stimulation of indigenous microbes by optimizing the water cut in low permeability reservoirs for green and enhanced oil recovery. We aimed to investigate the characteristics of indigenous bacterial communities with changes in water cut in reservoirs by high-throughput sequencing technology, and reveal the mechanism and characteristics of the crude oil biotreatment under different crude oil-water ratio conditions and the optimum activation time of indigenous functional microbial groups in reservoirs. The indigenous microbial metabolism products were characterized by gas chromatography mass spectrometry. Results showed that Acinetobacter (47.1%) and Pseudomones (19.8%) were the main functional genus of crude oil degradation at the optimal activation time, and can reduce the viscosity of crude oil from 8.33 to 5.75 mPa·s. The dominant bacteria genus for oil recovery after activation of the production fluids was similar to those in the reservoirs with water cut of 60-80%. Furthermore seven mechanism pathways of enhancing oil recovery by the synergistic of functional microbial groups and their metabolites under different water cut conditions in low permeability reservoirs have been established.

7.
Sci Rep ; 9(1): 16612, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719633

RESUMO

The aim of the study was to evaluate the ruminal function and microbial community of lamb under different nutrient levels. Sixty-four lambs with similarity body weight were randomly assigned to four groups after weaning off ewe's milk on the 17th day (6.2 ± 0.2 kg). The lambs of the control group (CON) were fed a basal diet, and the other three groups were subjected to a diet of decreased protein (PR), digestible energy (ER) or both of them at 20% (BR) of basal diet. The decrease of dietary protein or energy level decreased the average daily gain, ruminal weight and mucosal thickness of lambs (P < 0.05). The total volatile fatty acid (TVFA), acetate and propionate concentration of the CON group were significantly higher than that of the other three groups. The dietary protein and energy level affected the microbial diversity, and low energy level increased the relative abundance of phyla of Fibrobacteres, whereas at the genus level, increased the relative abundance of Butyrivibrio and Prevotellaceae. Under different dietary energy and protein levels, 14 genera exhibited significant correlation with ruminal fermentation. These findings supplied new perspective for the understanding of the dietary effect on ruminal microbial community interactions and are of great significance for establishing the optimal nutrient supply strategy for lambs.

8.
Medicine (Baltimore) ; 98(48): e18205, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770278

RESUMO

BACKGROUND AND OBJECTIVES: This meta-analysis was to investigate the efficacy and safety of new oral anticoagulant (NOAC) in atrial fibrillation (AF) patients with renal function insufficiency, and to explore whether renal decline occurs in AF patients with NOAC and its impact on outcomes. METHODS AND RESULTS: In AF patients with mild renal insufficiency, the NOAC was associated with significantly lower rates of stroke (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.91; P < .05). Lower rates of bleeding were significantly observed in NOAC group (OR, 0.85; 95% CI, 0.75-0.97; P < .05). In AF patients with moderate renal impairment, similar results were revealed (OR for stroke or systemic embolism, 0.80; 95% CI, 0.67-0.95, P < .05; OR for major bleeding, 0.78; 95% CI, 0.59-1.03; P = .07). During the follow-up, pooled data revealed that NOAC showed a less renal toxicity, but the difference did not reach statistical significance (creatinine clearance decline: -0.12 mL/min [-0.84, 0.61 mL/min]). We have revealed that the NOACs were associated with significantly lower rates of stroke or systemic embolism (hazard ratio [HR], 0.66; 95% CI, 0.42-0.89; P < .05) and lower rates of bleeding (HR, 0.93; 95% CI, 0.70-1.16; P = .153) in AF patients with worsening renal function. CONCLUSIONS: NOAC may have the potentiality to be at least as effective as warfarin and may equal safety outcomes in AF patients with renal impairment. Renal decline during therapeutics may be less likely happened in NOAC than warfarin dose. NOAC may reveal good efficacy and safety outcomes in these scenarios. Further detailed research is needed to gain more clear profile on this new anticoagulant.


Assuntos
Anticoagulantes , Fibrilação Atrial , Insuficiência Renal/complicações , Anticoagulantes/classificação , Anticoagulantes/farmacologia , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Humanos , Farmacovigilância , Resultado do Tratamento
9.
Animals (Basel) ; 9(10)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635360

RESUMO

Sixty neonatal Hu lambs were weaned at either 21 (n = 30) (early weaning, EW) or 49 days (n = 30) of age (control, CON). The starter intake and body weight (BW) of lambs was recorded weekly from birth to 63 days of age. Diarrhea rate of lambs was measured from birth to 35 days. Six randomly selected lambs from each treatment were slaughtered at 26, 35, and 63 days of age, respectively. Ruminal pH, NH3-N, and volatile fatty acid (VFA) concentration, as well as serum parameters including immunity, antioxidant status, and inflammatory parameters from randomly selected lambs from each treatment were measured. There was no difference in BW at birth and day 21 between the two groups of lambs (p > 0.05). However, BW of the lambs in the EW group was significantly lower than those in the CON group (p < 0.01) from 28 to 49 days of age. Average daily gain (ADG) of the lambs in the EW group was significantly lower than those in the CON group (p < 0.01) at three weeks after early weaning. Starter intake of the lambs in the EW group was obviously higher than that in the CON group (p < 0.01) from day 28 to 49. In addition, the diarrhea rate was significantly higher than that in the CON group from day 5 to 14 after weaning (p < 0.01). The EW group had heavier carcasses (p < 0.01) and rumen relative to whole stomach weights (p < 0.01). Rumen pH was increased by age (p < 0.01) and was not affected by early weaning (p > 0.05). Early weaning decreased abomasum relative to whole stomach weight (p < 0.01) and increased total VFA concentrations (p < 0.01) at day 26. There was no difference in lambs' immunity and stress indicators (p > 0.05). The results indicated that lambs weaned at 21 days of age had decreased ADG and higher diarrhea rate, although the overall immunity was not compromised. Long-term study is needed to further validate the feasibility of early weaning strategy in lambs.

10.
J Phys Chem B ; 123(43): 9222-9229, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31589039

RESUMO

Scaled-charge force fields (FFs) are widely employed in the simulation of neat ionic liquids (ILs), where the charges on the ions are empirically scaled to approximately account for electronic polarization and/or charge transfer. Such charge scaling has been found to yield significant improvement in liquid-state thermodynamic and dynamic properties (when compared to experiment). However, the mean field approximation inherent in charge scaling becomes suspect when applied to IL mixtures or solutions. In this work, we simulate solutions of IL with various nonpolar and polar gas solutes and compare results of charge-scaled and polarizable FFs to experiment. Our results demonstrate that scaling of the Coulomb interaction inherent in scaled-charge FFs leads to an underestimation of the solute-solvent electrostatic interaction and thus also the enthalpy and free energy of solvation; this effect is particularly pronounced for polar solutes. In some cases, we find that this artificial reduction in the solute-solvent interaction can also alter the apparent phase behavior of the resulting solution. Overall, the totality of our results suggests that explicit polarization (rather than charge scaling) is likely necessary to provide high transferability to both neat IL and IL mixtures and solutions.

11.
Nanotechnology ; 31(8): 084001, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31618713

RESUMO

A fluorine-doped, chlorine-intercalated carbon nitride (CNF-Cl) photocatalyst has been synthesized for simultaneous improvements in light harvesting capability along with suppression of charge recombination in bulk g-C3N4. The formation of heterojunctions of these CNF-Cl nanosheets with low bandgap, earth abundant bismuth oxyiodide (BiOI) was achieved, and the synthesized heterojunctions were tested as active photoanodes in photoelectrochemical water splitting experiments. BiOI/CNF-Cl heterojunctions exhibited extended light harvesting with a band-edge of 680 nm and generated photocurrent densities approaching 1.3 mA cm-2 under AM1.5 G one sun illumination. Scanning Kelvin probe force microscopy under optical bias showed a surface potential of 207 mV for the 50% BiOI/CNF-Cl nanocomposite, while pristine CNF-Cl and BiOI had surface photopotential values of 83 mV and 98 mV, respectively, which in turn, provided direct evidence of superior charge separation in the heterojunction blends. Enhanced charge carrier separation and improved light harvesting capability in BiOI/CNF-Cl hybrids were found to be the dominant factors in increased photocurrent, compared to the pristine constituent materials.

12.
Ther Adv Med Oncol ; 11: 1758835919876196, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31579127

RESUMO

Renal transplantation has become the sole most preferred therapy modality for end-stage renal disease patients. The growing tendency for renal transplants, and prolonged survival of renal recipients, have resulted in a certain number of post-transplant colorectal cancer patients. Antitumor pharmacotherapy in these patients is a dilemma. Substantial impediments such as carcinogenesis of immunosuppressive drugs (ISDs), drug interaction between ISDs and anticancer drugs, and toxicity of anticancer drugs exist. However, experience of antitumor pharmacotherapy in these patients is limited, and the potential risks and benefits have not been reviewed systematically. This review evaluates the potential impediments, summarizes current experience, and provides potential antitumor strategies, including adjuvant, palliative, and subsequent regimens. Moreover, special pharmaceutical care, such as ISDs therapeutic drug monitoring, metabolic enzymes genotype, and drug interaction, are also highlighted.

13.
Materials (Basel) ; 12(18)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527395

RESUMO

Copper-chromium alloy film and Cu-Cr bulk alloy were obtained using magnetron sputtering and vacuum smelting. Experimental results indicated that Cu-Cr bulk alloy and alloy films having different residual stress and atomic diffusion exhibit a significant difference in microstructure evolution behaviors after annealing. Numerous polyhedral Cu particles and dendritic Cr particles precipitated on the surface of annealed Cu-Cr alloy film and as-cast Cu-Cr bulk alloy, respectively. Cu particles were formed under the driving of energy and residual stress in the film. The effect of annealing temperature and Cr content on the size and quantity of Cu particles is discussed. Cr particles precipitated on the bulk alloy due to the low solid solubility of Cr in Cu, and the crystallinity of Cu grains promoted the diffusion of Cr atoms. The surface-enhanced Raman scattering (SERS) intensity of the Cu-14.6%Cr alloy film was obviously higher than that of the Cu-14.2%Cr bulk alloy. The particles/film composite structure possessed the appropriate particle number, surface roughness, and interstitial gap, as opposed to the bulk material, to effectively improve SERS enhancement.

14.
Vet Microbiol ; 235: 199-208, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383303

RESUMO

Trueperella pyogenes is an importantly opportunistic and commensal pathogen that causes suppurative lesions of most economically important livestock. To understand the molecular mechanism underlying the infection by T. pyogenes, we carried out a large-scale transcriptome sequencing of mice livers intraperitoneally infected with T. pyogenes using RNA-sequencing. A total of 47 G clean bases were obtained and 136 differentially expressed genes were detected between the control and the infection groups in the liver transcriptomes. Additionally, we found that the expression of a key autophagy regulator, mTOR (mechanistic target of rapamycin) was significantly up-regulated in the infection groups. Mechanistically, T. pyogenes infection induced the expression of mTOR and subsequently inhibited the autophagy of host cell. Blocking autophagy with inhibitor 3-methyladenine (3-MA) or silencing autophagy-related gene 7 (Atg7) reduced the effect of bacterial elimination. Interestingly, inhibition of mTOR induced autophagy and reduced T. pyogenes viability in RAW264.7 murine macrophages. The silencing mTOR regulated oxidation and cytokines (interleukin-1ß, IL-6 and tumor necrosis factro-α) against T. pyogenes in macrophages and significantly protected mice from T. pyogenes challenge. These findings indicate that mTOR is a novel functional regulator in autophagy-mediated T. pyogenes elimination and will be useful to further knowledge on the development of effective therapeutic strategy to control T. pyogenes-related diseases.


Assuntos
Autofagia , Infecções por Bactérias Gram-Positivas/imunologia , Serina-Treonina Quinases TOR/imunologia , Actinomycetaceae , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Proteína 7 Relacionada à Autofagia/genética , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Inativação Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Fígado/microbiologia , Macrófagos/imunologia , Camundongos
15.
J BUON ; 24(3): 913-917, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424642

RESUMO

PURPOSE: Long non-coding RNAs (lncRNA) polymorphisms have been reported to associate with the carcinogenicity mechanisms. The association between lncRNA H19 polymorphisms and the risk of non-small cell lung cancer (NSCLC) in Chinese population has not been reported yet. We designed this case-control study to evaluate the effects of H19 polymorphisms on NSCLC susceptibility. METHODS: In this case-control study, four single nucleotide polymorphisms (SNPs) (rs2067051, rs217727, rs2839698 and rs4929984) in H19 gene were genotyped in a Chinese population which consisted of 564 NSCLC cases and 1536 controls. RESULTS: rs2067051 was associated with a significantly decreased risk of NSCLC in our population [AA vs. GG: adjusted odds ratio (OR) = 0.75, 95% confidence interval (CI)=0.60-0.93; Additive model: OR=0.79, 95%CI=0.67-0.93)]. rs217727 was related to significantly increased NSCLC susceptibility (TT vs. CC: OR=1.16, 95%CI=1.01-1.33; Additive model: OR=1.16, 95%CI=1.01-1.33). However, no significant association was observed between rs2839698, rs4929984 and NSCLC risk. CONCLUSIONS: H19 polymorphism rs2067051 and rs217727 might influence NSCLC susceptibility and the mechanism warrants further exploration.

16.
Environ Sci Pollut Res Int ; 26(29): 29585-29596, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31440974

RESUMO

An exhaustive overview of heavy metal pollution in Chaohu Lake illustrating enrichment intensity, temporal and spatial distribution, chemical speciation, and ecological risk under natural and anthropogenic changes was conducted. Low concentrations of heavy metals excluding Hg were found in water whereas high Hg might be ascribed to surrounding coal-fired power plants. Copper, Pb, Zn, Cd, and Hg were enriched in sediment whereas Cr and Ni were comparable to background values. Besides, As demonstrated an equal accumulation from natural and anthropogenic fluxes. Heavy metals were at a low level prior to the 1950s; it increased gradually during the 1950s-1960s owing to population growth and agricultural expansion; then it displayed abrupt increase since the late 1970s due to rapid modern urbanization and industrialization and agricultural intensification. Spatial distribution of heavy metals was a good indicator of natural and anthropogenic changes, where higher enrichment was found in the western lake. Apart from fluvial input, anthropogenic disturbances such as land use changes, atmospheric deposition, and algae-derived organic matter, along with natural stressors including climate change, hydrological alteration, and soil erosion, made significant contribution to the biogeochemical cycle of heavy metals in the lake. Heavy metals mainly from anthropogenic sources were dominantly partitioned in non-residual fractions, whereas those mainly from natural sources were predominantly distributed in residual form. Mercury and Cd were below the threshold effect concentration (TEC) indicating that adverse effects were excluded. However, result of chemical speciation demonstrated Cd would pose a considerable potential ecological risk. Besides, most of the heavy metals were in the range of TEC-PEC suggesting possible toxicity.


Assuntos
Sedimentos Geológicos/análise , Lagos/análise , Metais Pesados/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental , Sedimentos Geológicos/química , Indústrias , Lagos/química , Solo , Análise Espaço-Temporal , Urbanização
17.
J Sex Med ; 16(10): 1506-1517, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31439521

RESUMO

BACKGROUND: Hyperhomocysteinemia (HHcy) has been reported to be strongly correlated with the occurrence of erectile dysfunction (ED), but the mechanisms are not fully understood. Moreover, whether melatonin could be a potential treatment of HHcy-induced ED needs to be elucidated. AIM: The aim of this study was to investigate the effects of melatonin on HHcy-induced ED and the potential mechanisms via modulating oxidative stress and apoptosis. METHODS: The Sprague-Dawley (SD) rat model of HHcy was induced by 7% methionine (Met)-rich diets. 36 male SD rats were randomly distributed into 3 groups (n = 12 per group): control group, 7% Met group, and 7% Met + melatonin (Mel; 10 mg/kg, intraperitoneal injection) treatment group. After 4 weeks, the erectile function of all rats was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum were also analyzed by immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, Western blotting, and polymerase chain reaction. OUTCOMES: HHcy-induced ED rat models were successfully established, and Mel could preserve erectile function mainly through inhibiting oxidative stress via the Erk1/2/Nrf2/HO-1 signaling pathway and suppression of apoptosis. RESULTS: Erectile function was significantly reduced in the rats with HHcy compared with that in the control group and was ameliorated in the HHcy rats treated with Mel. Compared with the control group, the rats in the HHcy group showed the following: (1) higher levels of total plasma homocysteine; (2) fewer neuronal nitric oxide synthase-positive cells in the corpus cavernous; (3) higher levels of reactive oxygen species and malondialdehyde, higher expression levels of nicotinamide adenine dinucleotide phosphate oxidase, and lower activities of superoxide dismutase, indicating an overactivated oxidative stress; (4) lower expression levels of Erk1/2/Nrf2/HO-1 signaling pathway components; and (5) higher levels of apoptosis, as determined by the expression levels of Bax, Bcl-2, and caspase 3. Mel treatment improved the erectile response, as well as histologic and molecular alterations. CLINICAL TRANSLATION: Our study on a rodent model of HHcy provided evidence that Mel could be a potential therapeutic method for HHcy-related ED. CONCLUSIONS: Mel treatment improves erectile function in rats with HHcy probably by potential antioxidative stress activity. This finding provides evidence for a potential new therapy for HHcy-induced ED. Tang Z, Song J, Yu, Z, et al. Melatonin Treatment Ameliorates Hyperhomocysteinemia-Induced Impairment of Erectile Function in a Rat Model. J Sex Med 2019;16:1506-1517.

18.
Micron ; 123: 102680, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31146186

RESUMO

While electron tomography can be used to visualize objects at nanoscale, it is difficult to perform reproducible quantitative measurements. Here we measure the shape and size of nanoparticles (NPs) in three dimensions (3D) using electron tomography. We evaluated the accuracy of maximum Feret diameter (Feretmax), minimum Feret diameter (Feretmini) and volume of NPs measurements from reconstructed 3D images which were obtained from data acquired with varied electron dose. We perform both simulations and experiment to clarify what factors effect on the accuracy of the NP shape measurement. Based on the results, suitable reconstruction methods and threshold for binarization were evaluated. We also report comparison results obtained on exactly the same samples in two different laboratories.

19.
J Hazard Mater ; 375: 26-32, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31035183

RESUMO

The worldwide environmental occurrence of natural steroid estrogens has drawn increasing concerns. However, the fate of the estrogens, especially the α-isomer of estradiol, in the environmental matrices is still obscure. Using 14C-radioactively labelled forms of these estrogens can facilitate and is sometimes a prerequisite for studying their transformation and residual distribution in the environment, but the availability of labelled compounds (owing to commercially high prices or unavailable) hampers such studies. Here we developed simple and stable methods to synthesize 14C-labelled estradiol isomers and estrone using relatively low-priced [carboxyl-14C]-labelled sodium acetate as a precursor. The radiochemical syntheses started from an enol lactone, which was prepared from nandrolone by oxidation to open the A-ring followed by recyclization. Inversion of the 17ß-hydroxyl group into its 17α-form was achieved via the Walden inversion using the Mitsunobu reaction. [3-14C]-17ß-estradiol, [3-14C]-17α-estradiol, and [3-14C]-estrone were synthesized in five, six, and seven steps with an overall radiochemical yield of 17.4%, 16.2%, and 13.9%, respectively. The synthesized 14C-labelled compounds provide materials for studying the fate and behavior of estrogens in complex environmental matrixes and for further synthesis of their 14C-labelled sulfate and glucuronide conjugates.

20.
Nano Lett ; 19(5): 3344-3352, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-30974946

RESUMO

Bypass signaling activation plays a crucial role in the acquired resistance of gefitinib, the first targeted drug in the clinic to treat advanced non-small cell lung cancer. Although the inactivation of bypass signaling by small-molecule inhibitors or monoclonal antibodies may overcome gefitinib resistance, their clinical use has been limited by the complex production process and off-target toxicity. Here we show CuS nanoparticles (NPs) behaved as a photodynamic nanoswitch to specifically abrogate overactive bypass signaling in resistant tumor cells without interfering with the same signal pathways in normal cells. In representative insulin growth factor-1 receptor (IGF1R) bypass activation-induced gefitinib resistant tumors, CuS NPs upon near-infrared laser irradiation locally elevated reactive oxygen species (ROS) level in tumor cells, leading to the blockage of bypass IGF1R and its downstream AKT/ERK/NF-κB signaling cascades. Consequently, laser-irradiated CuS NPs sensitized tumors to gefitinib treatment and prolonged the survival of mice with no obvious toxicity. Laser-irradiated CuS NPs may serve as a simple and safe nanomedicine strategy to overcome bypass activation-induced gefitinib resistance in a specific and controllable manner and provide insights into the treatment of a myriad of other resistant tumors in the field of cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Nanopartículas/química , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Humanos , Camundongos , Mutação , Ensaios Antitumorais Modelo de Xenoenxerto
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