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1.
J Chem Phys ; 160(21)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38832730

RESUMO

It is highly demanded to understand the confinement effect on nanoconfined polymers. Recent studies reported a strong perturbation of local dynamics and substantial alteration of glass transition temperature Tg at nanoscale. However, how confinement affects the mechanical properties of polymers is not fully understood. Here, we show that the modulus of thin polymer films could be remarkedly altered through a polymer-polymer interface. The modulus of a thin polystyrene (PS) film next to a polydimethylsiloxane (PDMS) was determined from the PS-PDMS bilayer bulging test. A series of experiments show that the modulus of PS can be increased up to 37%, when the modulus of the neighboring PDMS varies from 1.04 to 4.88 MPa. The results demonstrate a strong sensitivity of mechanical properties of thin polymers to the hard/soft environment, which we attribute to the change of high-mobility layer by the polymer-polymer interface.

2.
Int J Impot Res ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858529

RESUMO

Erectile dysfunction is a common sexual disorder in men. Some studies have found a strong association between some serum metabolites and erectile dysfunction. To investigate this association further, we used bidirectional Mendelian randomisation to investigate causality and possible biological mechanisms.Firstly, this study screened the statistics of genome-wide association studies of serum metabolites and erectile dysfunction to obtain instrumental variables. Inverse variance weighting was used as the primary method for causal effect analysis of instrumental variables in forward or reverse Mendelian randomisation, and the results obtained by MR-Egger regression and the weighted median method were used as references. Subsequently, the metabolites causally associated with erectile dysfunction were subjected to replication analyses and meta-analyses, and the results of the meta-analyses were analysed by pathway analyses to find influential pathways. In this process, Mendelian randomisation results need to be assessed for stability and reliability using sensitivity analysis.It was found that a total of six serum metabolites were causally associated with erectile dysfunction in a forward Mendelian randomisation study. 1,3,7-trimethyluraten (0.85 (0.73-0.99), P = 0.0368), ergothioneine (0.65 (0.45-0.94), P = 0.0226) and gamma-glutamylglutamate (0.63 (0.46-0.88), P = 0.0059) were protective against the development of erectile dysfunction, whereas 2-hydroxyhippurate (1.10 (1.02-1.19), P = 0.0152), N2,N2-dimethylguanosine (1.57 (1.02-2.40), P = 0.0395) and octanoylcarnitine (1.38 (1.06-1.82), P = 0.0183) were able to induce the development of erectile dysfunction. In addition, metabolic pathway analysis showed that 1,3,7-trimethylurate was able to influence the development of erectile dysfunction via the caffeine metabolism pathway (P = 0.0454). On the other hand, reverse Mendelian randomisation analysis showed that erectile dysfunction reduced serum homocitrulline levels (0.99 (0.97-1.00), P = 0.0360). Sensitivity analyses, including heterogeneity tests and pleiotropy tests, confirmed the reliability of the results.In conclusion, this study demonstrated a bidirectional causal relationship between serum metabolites and erectile dysfunction using bidirectional Mendelian randomisation analysis and replication meta-analysis. On this basis, this study provides a new direction of thinking and strong evidence for the therapeutic application and adjunctive diagnosis of serum metabolites in erectile dysfunction, and provides a certain reference value for subsequent related studies.

3.
Gut Microbes ; 16(1): 2316533, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38372783

RESUMO

Probiotics are live microorganisms that offer potential benefits to their hosts and can occasionally influence behavioral responses. However, the detailed mechanisms by which probiotics affect the behavior of their hosts and the underlying biogenic effects remain unclear. Lactic acid bacteria, specifically Lactobacillus spp. are known probiotics. Drosophila melanogaster, commonly known as the fruit fly, is a well-established model organism for investigating the interaction between the host and gut microbiota in translational research. Herein, we showed that 5-day administration of Lactobacillus acidophilus (termed GMNL-185) or Lacticaseibacillus rhamnosus (termed GMNL-680) enhances olfactory-associative memory in Drosophila. Moreover, a combined diet of GMNL-185 and GMNL-680 demonstrated synergistic effects on memory functions. Live brain imaging revealed a significant increase in calcium responses to the training odor in the mushroom body ß and γ lobes of flies that underwent mixed feeding with GMNL-185 and GMNL-680. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and whole-mount brain immunohistochemistry revealed significant upregulation of lactate dehydrogenase (LDH) expression in the fly brain following the mixed feeding. Notably, the genetic knockdown of Ldh in neurons, specifically in mushroom body, ameliorated the beneficial effects of mixed feeding with GMNL-185 and GMNL-680 on memory improvement. Altogether, our results demonstrate that supplementation with L. acidophilus and L. rhamnosus enhances memory functions in flies by increasing brain LDH levels.


Assuntos
Drosophila , Microbioma Gastrointestinal , Animais , Lactobacillus , Drosophila melanogaster , Corpos Pedunculados , Encéfalo , Lactato Desidrogenases
4.
Se Pu ; 42(2): 159-163, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38374596

RESUMO

Peak alignment is a crucial data-processing step in untargeted metabolomics analysis that aims to integrate metabolite data from multiple liquid chromatography-mass spectrometry (LC-MS) batches for enhanced comparability and reliability. However, slight variations in the chromatographic separation conditions can result in retention time (RT) shifts between consecutive analyses, adversely affecting peak alignment accuracy. In this study, we present a retention index (RI)-based chromatographic peak-shift correction (CPSC) strategy to address RT shifts and align chromatographic peaks for metabolomics studies. A series of N-acyl glycine homologues (C2-C23) was synthesized as calibrants, and an LC RI system was established. This system effectively corrected RT shifts arising from variations in flow rate, gradient elution, instrument systems, and chromatographic columns. Leveraging the RI system, we successfully adjusted the RT of raw data to mitigate RT shifts and then implemented the Joint Aligner algorithm for peak alignment. We assessed the accuracy of the RI-based CPSC strategy using pooled human fecal samples as a test model. Notably, the application of the RI-based CPSC strategy to a long-term dataset spanning 157 d as an illustration revealed a significant enhancement in peak alignment accuracy from 15.5% to 80.9%, indicating its ability to substantially improve peak-alignment precision in multibatch LC-MS analyses.


Assuntos
Algoritmos , Metabolômica , Humanos , Reprodutibilidade dos Testes , Cromatografia Líquida , Espectrometria de Massa com Cromatografia Líquida
5.
J Chem Phys ; 159(21)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38054519

RESUMO

The demand for applications, such as coatings, separation filters, and electronic packaging, has greatly driven the research of polymer films. At nanometer scale, mechanical properties of thin polymer films can significantly deviate from bulk. Despite outstanding progresses, there still lack deep discussions on nonlinear viscoelastic-viscoplastic response and their interactions under nanoconfinement. In this work, by conducting measurements via the bubble inflation method and modelling using Schapery and Perzyna equations, we demonstrate nonlinear viscoelastic-viscoplastic properties of freely standing thin polystyrene (PS) films. The results show the unchanged glassy compliance and the rubbery stiffening phenomenon for thin PS films, where the lower rubbery plateau in rubbery stiffening may originate from the induced molecular orientation by plastic deformation. With decreasing film thickness, viscosity and yield stress in viscoplasticity increase in an exponential and a linear trend, respectively, indicating the significant role of nanoconfinement effect on viscoplastic properties. These findings may reveal that there are many properties from linear viscoelasticity to nonlinear viscoelasticity-viscoplasticity that need to be explored and unveiled for sufficient understanding of the nanoconfinement effect on altering mechanical behavior of polymers.

6.
Hum Vaccin Immunother ; 19(3): 2281700, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38112061

RESUMO

The safety of human papillomavirus (HPV) vaccines, one of the major challenges to public vaccination, has been controversial. This study assessed the adverse reactions of 9-valent HPV (9vHPV) vaccines. This open-label, observational, multi-center, post-marketing study assessed the safety of 9vHPV administered according to local clinical practice. All post-marketing adverse events (AEs) reports received between December 2019 and November 2021 in Chongqing were analyzed. A total of 1000 individuals aged 16-26 years provided safety data post-vaccination; The most common AEs (60.1%) experienced by 9vHPV vaccine recipients were vaccination-site AEs (pain, swelling, induration) and non-vaccination-site AEs (dizzy, weak, fever). Vaccination-site AEs most were mild-to-moderate in intensity. Discontinuations and HPV 9-related serious AEs were rare (0.3% and 0.0%, respectively). Eight SAEs were reported during the study but none were considered as related to the study vaccine. The 9vHPV vaccine was generally well tolerated in subjects aged 16-26 years; Vaccination-site AEs were more common with 9vHPV.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vigilância de Produtos Comercializados , Vacinação , Humanos , China , Dor/etiologia , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/uso terapêutico , Vacinação/efeitos adversos , Adolescente , Adulto Jovem , Adulto
7.
Anal Chem ; 95(35): 13330-13337, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37609864

RESUMO

Peak alignment is a crucial step in liquid chromatography-mass spectrometry (LC-MS)-based large-scale untargeted metabolomics workflows, as it enables the integration of metabolite peaks across multiple samples, which is essential for accurate data interpretation. Slight differences or fluctuations in chromatographic separation conditions, however, can cause the chromatographic retention time (RT) shift between consecutive analyses, ultimately affecting the accuracy of peak alignment between samples. Here, we introduce a novel RT shift correction method based on the retention index (RI) and apply it to peak alignment. We synthesized a series of N-acyl glycine (C2-C23) homologues via the amidation reaction between glycine with normal saturated fatty acids (C2-C23) as calibrants able to respond proficiently in both mass spectrometric positive- and negative-ion modes. Using these calibrants, we established an N-acyl glycine RI system. This RI system is capable of covering a broad chromatographic space and addressing chromatographic RT shift caused by variations in flow rate, gradient elution, instrument systems, and LC separation columns. Moreover, based on the RI system, we developed a peak shift correction model to enhance peak alignment accuracy. Applying the model resulted in a significant improvement in the accuracy of peak alignment from 15.5 to 80.9% across long-term data spanning a period of 157 days. To facilitate practical application, we developed a Python-based program, which is freely available at https://github.com/WHU-Fenglab/RI-based-CPSC.


Assuntos
Fabaceae , Cromatografia Líquida , Glicina , Espectrometria de Massas , Metabolômica
8.
Anal Chem ; 95(30): 11550-11557, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471289

RESUMO

Gut microbiota-host co-metabolites serve as essential mediators of communication between the host and gut microbiota. They provide nutrient sources for host cells and regulate gut microenvironment, which are associated with a variety of diseases. Analysis of gut microbiota-host co-metabolites is of great significance to explore the host-gut microbiota interaction. In this study, we integrated chemical derivatization, liquid chromatography-mass spectrometry, and molecular networking (MN) to establish a novel CD-MN strategy for the analysis of carboxylated metabolites in gut microbial-host co-metabolism. Using this strategy, 261 carboxylated metabolites from mouse feces were detected, which grouped to various classes including fatty acids, bile acids, N-acyl amino acids, benzoheterocyclic acids, aromatic acids, and other unknown small-scale molecular clusters in MN. Based on the interpretation of the bile acid cluster, a novel type of phenylacetylated conjugates of host bile acids was identified, which were mediated by gut microbiota and exhibited a strong binding ability to Farnesoid X receptor and Takeda G protein-coupled receptor 5. Our proposed strategy offers a promising platform for uncovering carboxylated metabolites in gut microbial-host co-metabolism.


Assuntos
Microbioma Gastrointestinal , Animais , Camundongos , Microbioma Gastrointestinal/fisiologia , Metaboloma , Fezes/química , Espectrometria de Massas/métodos , Aminoácidos/análise , Ácidos e Sais Biliares/análise
9.
J Hazard Mater ; 452: 131190, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36965353

RESUMO

Di(2-ethylhexyl) phthalate (DEHP), the most widely used plasticizers in the world, has been regarded as an endocrine disrupting chemical with serious adverse health outcomes. Accumulating evidence strongly suggests that the undesirable biological effects of DEHP are meditated by its metabolites rather than itself. However, the metabolic footprints of DEHP in vivo are still unclear. Here we developed a click chemistry-assisted mass spectrometry (CC-MS) strategy for in-depth profiling DEHP metabolites in rats. An alkyne-modified DEHP analogue (alkyne-DEHP) was synthesized as a tracer for in vivo tracing, and a pair of MS probes (4-azido-nphenylbenzamide, 4-ANPA, and its deuterated reagent d5-4-ANPA) were prepared to specifically label the alkyne-DEHP metabolites, and prominently improve their detection sensitivity and selectivity. Using the CC-MS strategy, we successfully screened 247 alkyne-DEHP metabolites from rat urine, feces, and serum, including many unrevealed metabolites, such as oxidized phthalate diester metabolites and glucuronides of phthalate monoester metabolites. The discovery of new DEHP metabolites provides additional insights for understanding the metabolism of DEHP, which may be beneficial in exploring the mechanism underlying DEHP induced-toxicity in the future.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Ratos , Animais , Química Click , Plastificantes/toxicidade , Plastificantes/metabolismo , Espectrometria de Massas , Indicadores e Reagentes
10.
Anal Chim Acta ; 1239: 340691, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628759

RESUMO

Bile acids (BAs) are a class of vital gut microbiota-host cometabolites, and they play an important role in maintaining gut microbiota-host metabolic homeostasis. Very recently, a new mechanism of BA anabolic metabolism mediated by gut microbiota (BA-amino acid conjugation) has been revealed, which provides a perspective for the research on BA metabolism and gut metabolome. In this study, we established a polarity-switching multiple reaction monitoring mass spectrometry-based screening method to mine amino acid-conjugated bile acids (AA-BAs) derived from host-gut microbiota co-metabolism. In addition, a retention time-based annotation strategy was further proposed to identify the AA-BA isomers and epimers. Using the developed methods, we successfully screened 118 AA-BA conjugates from mouse and human feces, 28 of them were confirmed by standards, and 62 putatively identified based on their predicted retention times. Moreover, we observed that the levels of most AA-BAs were significantly downregulated in the feces of chronic sleep deprivation mice, suggesting that the AA-BA metabolism was closely related to the physiological state of the host.


Assuntos
Aminoácidos , Ácidos e Sais Biliares , Camundongos , Humanos , Animais , Aminoácidos/análise , Cromatografia Líquida , Espectrometria de Massas , Ácidos e Sais Biliares/análise , Fezes/química
11.
Sci Adv ; 8(17): eabm3436, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35476440

RESUMO

Macrophages play a vital role in cardiac repair following myocardial infarction (MI). An enriched environment (EE) is involved in the regulation of macrophage-related activities and disease progression; however, whether EE affects the phenotype and function of macrophages to improve postinfarction cardiac repair remains unknown. In this study, we found that EE improved cardiac function, decreased mortality, and ameliorated adverse ventricular remodeling in mice after MI, with these outcomes closely related to the increased survival of Ly6Clow macrophages and their CCR2-MHCIIlow subsets. EE increased the expression of brain-derived neurotrophic factor (BDNF) in the hypothalamus, leading to higher circulating levels of BDNF, which, in turn, regulated the cardiac macrophages. BDNF bound to tropomyosin receptor kinase B to activate downstream ERK1/2 and AKT pathways, promoting macrophage survival. These findings demonstrate that EE optimizes postinfarction cardiac repair and highlights the significance of EE as a previously unidentified strategy for impeding adverse ventricular remodeling.


Assuntos
Infarto do Miocárdio , Remodelação Ventricular , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Coração , Macrófagos/metabolismo , Camundongos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/terapia , Miocárdio/metabolismo
12.
Bioorg Chem ; 121: 105679, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35182884

RESUMO

A phytochemical study was carried out on the extract of Trillium tschonoskii rhizomes, resulting in the isolation of thirty-six steroidal glycosides (1-36). Their structures were established mainly by spectroscopic analyses as well as necessary chemical evidence, of which 1-25 were identified as new analogues. Herein, all the isolated analogues were screened for the cytotoxicity against intrahepatic cholangiocarcinoma (ICC) cell lines of HuCCT1 and RBE through tumor colony formation and CCK-8 survival analysis, and the results demonstrated that three compounds 9, 12, and 26 significantly repressed tumor colony and sphere formation in both cell lines, respectively. Furthermore, the three analogues possessed a remarkable inhibitory role of organoid formation established from hydrodynamic induced mouse primary intrahepatic cholangiocarcinoma. Moreover, the functional assays of flow cytometry analysis, cancer stemness related gene expression, and western blotting assays all indicated that compound 26 could significantly repress cancer stem markers. Taken together, these results demonstrate that steroidal glycosides derived from T. tschonoskii rhizomes could be potentially implicated in human ICC therapy.


Assuntos
Colangiocarcinoma , Saponinas , Trillium , Animais , Proliferação de Células , Colangiocarcinoma/tratamento farmacológico , Glicosídeos/farmacologia , Camundongos , Rizoma/química , Saponinas/química , Saponinas/farmacologia , Trillium/química
13.
Anal Chem ; 94(5): 2655-2664, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35085440

RESUMO

Bile acids (BAs) are a type of gut microbiota-host cometabolites with abundant structural diversity, and they play critical roles in maintaining host-microbiota homeostasis. In this study, we developed a new N-(4-aminomethylphenyl) pyridinium (AMPP) derivatization-assisted alternating dual-collision energy scanning mass spectrometry (AMPP-dual-CE MS) method for the profiling of BAs derived from host-gut microbiota cometabolism in mice. Using the proposed method, we discovered two new types of amino acid conjugations (alanine conjugation and proline conjugation) and acetyl conjugation with host BAs, for the first time, from mouse intestine contents and feces. Additionally, we also determined and identified nine new leucine- and phenylalanine-conjugated BAs. These findings broaden our knowledge of the composition of the BA pool and provide insight into the mechanism of host-gut microbiota cometabolism of BAs.


Assuntos
Ácidos e Sais Biliares , Microbioma Gastrointestinal , Animais , Bile , Ácidos e Sais Biliares/análise , Fezes/química , Espectrometria de Massas , Camundongos
14.
Rev Sci Instrum ; 92(10): 103904, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34717382

RESUMO

We present the design and validation of an apparatus, which is developed based on micro-vibration in cyclic bulge and contraction, to determine dynamic mechanical properties of ultrathin polymer films. By controlling air pressure acting on a polymer membrane, the apparatus exerts simple harmonic or other type periodic stresses on the film, and the resultant real-time deformation of the freely standing film is recorded by using a high-speed CCD camera. From the image frame sequences and the gas pressure data, the real-time stress and strain of the polymer film are attained. Consequently, the dynamic mechanical properties, including biaxial storage and loss moduli, and loss factor can be determined for polymer films with thickness down to 20 nm. This apparatus could also be used to determine other mechanical properties such as fatigue and yield for nanoconfined films of soft matter.

15.
J Phys Chem Lett ; 12(33): 8072-8079, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34406018

RESUMO

Mastering mechanical properties of polymers at nanometer scale is highly demanded yet remains challenging. Pioneering advances determined Young's modulus in ultrathin polymer films and attained unprecedented results including rubbery stiffening. However, many viscoelastic properties such as dynamic mechanical behavior of freestanding nanoconfined polymer films are still unknown. Here we demonstrate striking changes of stiffness and the ratio between elastic and viscous responses in thin PDMS films, using a microvibrational system which enables direct measurements of dynamic stress-strain relation of freestanding films. The results show that elastic modulus is enhanced by a factor of 135 in 50 nm films than the bulk, while the viscous response substantially increases at strains >0.05 in 125 nm films. These observations exhibit significant alterations of viscoelasticity under nanoconfinement. With insights on the underlying mechanism of these results, this study is expected to provide new evidence toward gaining a comprehensive understanding of nanoconfinement effect of soft matter.


Assuntos
Elastômeros/química , Nanotecnologia , Dimetilpolisiloxanos/química , Elasticidade , Fenômenos Mecânicos , Membranas Artificiais , Viscosidade
16.
Curr Med Sci ; 41(1): 140-144, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582918

RESUMO

The effect of preoperative Double-J (DJ) ureteral stenting before flexible ureterorenoscopy (FURS) in the treatment for urinary stones was evaluated. We retrospectively enrolled 306 consecutive patients who underwent FURS from Jan. 2014 to Dec. 2017. All the patients were classified into two groups according to whether they had DJ ureteral stenting before FURS. Baseline characteristics (age, sex, stone location, stone size, surgical success rate, operation time, stone-free rate of the first day after surgery, stone-free rate of the first month after surgery, total complication rate) were compared using Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables. In total, 306 patients were included in this study. The group of DJ stenting before FURS included 203 (66.3%) patients, and non-DJ stenting before FURS was observed in 103 (33.7%) patients. The group of DJ stenting before FURS was significantly associated with a shorter operation time (53.8 vs. 59.3 min, P<0.001), a higher stone-free rate of the first day after surgery (69.0% vs. 51.5%, P=0.003). However, statistical significant differences were not found in the age, sex, stone location, stone size, surgical success rate, stone-free rate of the first month after surgery (89.2% vs. 81.6%, P=0.065) and total complication rate (5.4% vs. 9.7%, P=0.161) between the two groups. Preoperative DJ ureteral stenting before FURS could reduce the operation time and increase stone-free rate of the first day after surgery. However, it might not benefit the stone-free rate of the first month after surgery and reduce the complication rate. Preoperative DJ stenting should be not routinely performed.


Assuntos
Complicações Pós-Operatórias/epidemiologia , Ureteroscopia/métodos , Cálculos Urinários/cirurgia , Cateterismo Urinário/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Ureteroscopia/efeitos adversos , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/instrumentação , Cateteres Urinários/efeitos adversos , Cateteres Urinários/normas
17.
Mol Cell Biochem ; 463(1-2): 137-146, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31595425

RESUMO

Coronin-3 (coronin-1C), a homotrimer F-actin-binding protein, has been reported to be important for metastasis in several types of cancers such as lung cancer, gastric cancer, and breast cancer. Here, we present an investigation of the expression and function of coronin-3 in renal cell cancer for the first time. We also confirmed that miR-26 directly targets coronin-3 and down-regulates its expression by western blot assay and dual-luciferase reporter system. The results of MTT and colony formation assay showed that miR-26 suppressed cell proliferation. Wound healing and transwell assay revealed that miR-26 inhibited migration and invasion of renal cancer cell. Moreover, overexpression of coronin-3 could reverse the miR-26-induced inhibition in cell growth and metastasis. Thus, our study suggests that coronin-3 should serve as a potential therapeutic target in renal cell cancer and provide a candidate for miRNA therapy.


Assuntos
Movimento Celular , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/metabolismo , MicroRNAs/metabolismo , Proteínas dos Microfilamentos/biossíntese , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/metabolismo , Células HEK293 , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , MicroRNAs/genética , Proteínas dos Microfilamentos/genética , Proteínas de Neoplasias/genética , RNA Neoplásico/genética
18.
J BUON ; 24(1): 227-232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30941974

RESUMO

PURPOSE: To determine the associations among diabetes status, Metformin administration and prostate cancer (PCa) detection at biopsy in Chinese population. METHODS: A case-control study was conducted among a prospectively enrolled prostate biopsy cohort of 518 patients from Jan 2013 to Dec 2014 at our institute. Diabetes status and Metformin administration were determined through medical records and self-report. Different clinical characteristics were registered and compared among different groups. Univariate and multivariate logistic regression analyses were performed to evaluate the effects of diabetes status and Metformin administration on the detection of overall as well as high-grade PCa at biopsy. RESULTS: PCa was detected in 229 (44.2%) men, and high-grade PCa (Gleason score ≥8) was detected in 65 (12.5%) men. Diabetes was observed in 96 men, and 28 of them were administered with Metformin. Both overall and high-grade cancer detection rates were significantly higher in diabetic patients (p<0.001). In multivariate analysis, diabetes status was a risk factor for high-grade cancer detection (OR 7.699, 95%CI 3.483-17.020, p<0.001), but not for total PCa detection (OR 1.774, 95%CI 0.831-3.787, p=0.138). Meanwhile, Metformin administration was proved to be a protective factor for high-grade disease (OR 0.420, 95%CI 0.201-0.879, p=0.021) in multivariate analysis, while no correlation was detected with overall cancer detection (OR 0.786, 95%CI 0.172-3.593, p=0.756). CONCLUSIONS: Diabetes status was positively associated with biopsy-mediated high-grade PCa detection in Chinese population, while the positive association would be partly compromised by Metformin administration.


Assuntos
Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Neoplasias da Próstata/prevenção & controle , Substâncias Protetoras/administração & dosagem , Idoso , Biópsia , Estudos de Casos e Controles , China , Diabetes Mellitus , Seguimentos , Humanos , Masculino , Gradação de Tumores , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico
19.
Zhonghua Nan Ke Xue ; 25(5): 309-314, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32216211

RESUMO

OBJECTIVE: To investigate the effects of melatonin on the oxidative stress and signaling pathways of apoptosis-related genes following testicular torsion/detorsion in male rats. METHODS: Twenty-four healthy male Sprague-Dawley rats were randomly divided into a control, a torsion and a melatonin group of equal number. The torsion model was made in the animals of the latter two groups by 720° torsion of the left testis for 2 hours. The rats of the torsion and melatonin groups received intraperitoneal injection of isotonic saline and melatonin (17 mg/kg) respectively at 15 minutes prior to detorsion. At 24 hours after modeling, testis tissues were collected from the rats for detection of the apoptosis of the germ cells by flow cytometry (FCM), analysis of the expressions of Fas, Fas ligand (FasL) and Bax mRNA by quantitative real-time PCR (qRT-PCR), measurement of the cytochrome C content released from the mitochondrion by Western blot, and determination of the total antioxidant capacity (T-AOC) and the levels of myeloperoxidase (MPO) and malodialdehyde (MDA) by spectrophotometry. RESULTS: Compared with the torsion group, the rats treated with melatonin showed significantly increased normal testicular cells (ï¼»77.81 ± 6.52ï¼½% vs ï¼»88.61 ± 7.93ï¼½%, P < 0.05), decreased early apoptotic germ cells (ï¼»16.74 ± 3.16ï¼½% vs ï¼»6.97 ± 1.65ï¼½%, P < 0.05), down-regulated expressions of Fas (ï¼»4.52 ± 0.29ï¼½ vs ï¼»2.66 ± 0.37ï¼½, P < 0.01), FasL (ï¼»2.82 ± 0.30ï¼½ vs ï¼»1.73 ± 0.18ï¼½, P < 0.01) and Bax mRNA (ï¼»2.39 ± 0.18ï¼½ vs ï¼»1.50 ± 0.14ï¼½, P < 0.01), reduced levels of cytochrome C (ï¼»1.40 ± 0.38ï¼½ vs ï¼»0.67 ± 0.30ï¼½, P < 0.01), MPO (ï¼»0.52 ± 0.15ï¼½ vs ï¼»0.19 ± 0.10ï¼½ U/g prot, P < 0.01) and MDA ï¼»6.37 ± 1.73ï¼½ vs ï¼»3.98 ± 0.90ï¼½ nmol/mg prot, P < 0.01) and elevated T-AOC (ï¼»0.76 ± 0.25ï¼½ vs ï¼»1.55 ± 0.32ï¼½ U/mg prot, P < 0.01). CONCLUSIONS: Melatonin has a significant protective effect on spermatogenesis after testicular torsion by regulating the expressions of apoptosis-related genes and increasing T-AOC in the testis tissue.


Assuntos
Apoptose , Melatonina/uso terapêutico , Estresse Oxidativo , Transdução de Sinais , Torção do Cordão Espermático/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Masculino , Malondialdeído , Ratos , Ratos Sprague-Dawley , Espermatogênese/efeitos dos fármacos , Testículo
20.
Materials (Basel) ; 11(8)2018 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30061504

RESUMO

In this research, the effect of several heat treatments on the microstructure and microhardness of TC4 (Ti6Al4V) titanium alloy processed by selective laser melting (SLM) is studied. The results showed that the original acicular martensite α'-phase in the TC4 alloy formed by SLM is converted into a lamellar mixture of α + ß for heat treatment temperatures below the critical temperature (T0 at approximately 893 °C). With the increase of heat treatment temperature, the size of the lamellar mixture structure inside of the TC4 part gradually grows. When the heat treatment temperature is above T0, because the cooling rate is relatively steep, the ß-phase recrystallization transforms into a compact secondary α-phase, and a basketweave structure can be found because the primary α-phase develop and connect or cross each other with different orientations. The residence time for TC4 SLM parts when the treatment temperature is below the critical temperature has little influence: both the α-phase and the ß-phase will tend to coarsen but hinder each other, thereby limiting grain growth. The microhardness gradually decreases with increasing temperature when the TC4 SLM part is treated below the critical temperature. Conversely, the microhardness increases significantly with increasing temperature when the TC4 SLM part is treated above the critical temperature.

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