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1.
J Agric Food Chem ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065523

RESUMO

2-Ethyl-3,5(3,6)-dimethylpyrazine (EDMPs) has a pleasant aroma of roasted cocoa or nuts with extreme low odor threshold that have potential in industrial applications as food fragrances. Food fermentation process can accumulate EDMPs and that might be the chance to study the biosynthesis mechanism of EDMPs under mild conditions for "natural" EDMPs' production. In this study, an EDMP-producing strain was isolated from Baijiu fermentation. This strain was identified as Bacillus subtilis, a generally regarded as safe (GRAS) organism. After reasonable assumption, substrate addition and isotope-labelled experiments, we found EDMPs are produced from L-threonine and D-glucose at environmental temperature and pressure. In addition, aminoacetone, metabolite of L-threonine, and 2,3-pentanedione, metabolite of L-threonine and D-glucose, are intermediates for the production of EDMPs. This study proposed and confirmed the biosynthesis pathway of EDMPs. It will be helpful for the industrial production of EDMPs, and provides reference for the biosynthetic mechanism analysis of other valuable pyrazines.

2.
Medicine (Baltimore) ; 99(8): e19246, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080128

RESUMO

INTRODUCTION: Chromosome 6pter-p24 deletion syndrome (OMIM #612582) is a rare genetic disorder characterized by deletion of the distal part of 6p. Human 6p deletion syndromes result in a variety of congential malformations. PATIENT CONCERNS: The fetus was the fourth child born to healthy non-consanguineous parents with no relevant family history. DIAGNOSIS: The fetus was diagnosed with 6pter-p24 deletion syndrome through prenatal ultrasound, magnetic resonance imaging, and chromosomal microarray analysis. The fetus had brain, skeletal, and heart malformations. The fetus was cytogenetically normal. Chromosomal microarray analysis detected an interstitial 7.999Mb deletion within the 6p25.1p24.3 region of chromosome 6. INTERVENTIONS: There was no treatment for the fetus. OUTCOMES: Pregnancy was terminated. CONCLUSIONS: To the author's knowledge, the present case is one of the first to report the prenatal diagnosis of 6pter-p24 deletion syndrome in a fetus. No published reports have described the diagnosis of 6pter-p24 deletion syndrome using multiple technologies during the antenatal period; therefore, our findings may provide a reference for other clinicians. The clinical features and pathophysiology of this prenatal diagnosis are discussed.

3.
J Cell Mol Med ; 24(1): 686-694, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31691506

RESUMO

Type 2 diabetes mellitus (T2DM) is the most common diabetes and has numerous complications. Recent studies demonstrated that T2DM compromises bone fracture healing in which miR-222 might be involved. Furthermore, tissue inhibitor of metalloproteinase 3 (TIMP-3) that is the target of miR-222 accelerates fracture healing. Therefore, we assume that miR-222 could inhibit TIMP-3 expression. Eight-week-old rats were operated femoral fracture or sham, following the injection of streptozotocin (STZ) to induce diabetes one week later in fractured rats, and then, new generated tissues were collected for measuring the expression of miR-222 and TIMP-3. Rat mesenchymal stem cells (MSCs) were isolated and treated with miR-222 mimic or inhibitor to analyse osteogenic differentiation. MiR-222 was increased in fractured rats and further induced in diabetic rats. In contrast, TIMP-3 was reduced in fractured and further down-regulated in diabetic rats. Luciferase report assay indicated miR-222 directly binds and mediated TIMP-3. Furthermore, osteogenic differentiation was suppressed by miR-222 mimic and promoted by miR-222 inhibitor. miR-222 is a key regulator that is promoted in STZ-induced diabetic rats, and it binds to TIMP3 to reduce TIMP-3 expression and suppressed MSCs' differentiation.

4.
Cell Tissue Res ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31867684

RESUMO

Among the troika of clinicopathologic features of asthma, airway remodelling has gained sufficient attention for its contribution to progressive airway narrowing. Much effort has been directed at the management of airway smooth muscle cells (ASMCs), but few attempts have proven to prevent the progression of remodelling. Recently, accumulating data have shown the anti-inflammatory/anti-proliferative potency of melatonin (a crucial neurohormone involved in many physiological and pathological processes) in diverse cells. However, no evidence has confirmed its effect on ASMCs. The present study investigates the benefits of melatonin in asthma, with an emphasis on airway remodelling. The results indicated that melatonin significantly attenuated airway hyperresponsiveness (AHR), inflammation and remodelling in a house dust mite (HDM) model. Melatonin markedly alleviated goblet cell hyperplasia/metaplasia, collagen deposition and airway smooth muscle hyperplasia/hypertrophy, implying the achievement of remodelling remission. The data obtained in vitro further revealed that melatonin notably inhibited ASMCs proliferation, VEGF synthesis and cell migration induced by PDGF, which might depend on STAT3 signalling. Moreover, melatonin remarkably relieved ASMCs contraction and reversed ASMCs phenotype switching induced by TGF-ß, probably via the Akt/GSK-3ß pathway. Altogether, our findings illustrated for the first time that melatonin improves asthmatic airway remodelling by balancing the phenotypic proportions of ASMCs, thus highlighting a novel purpose for melatonin as a potent option for the management of asthma.

5.
PLoS One ; 14(11): e0225463, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751406

RESUMO

OBJECTIVE: The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. The pathogenic mechanisms that damage the fetal-maternal unit and cause abnormal placental development are incompletely understood in APS patients. Liquid Chromatography/Mass Spectrometry (LC/MS) based metabolomics are applied for the mechanism of disease and further supporting the research of diagnosis and management in recent years. The aim of this research was to investigate the difference of serum metabolic profiles in recurrent abortion women with APS and healthy women to explore the mechanism of this disease. METHODS: Serum samples of 25 recurrent abortion women with APS and 25 healthy women were collected and analyzed by LC/MS in this study. Potential biomarkers were discovered by multivariate statistical analysis and then identified based on analysis results. RESULTS: Totally, we identified five biomarkers that involved in different metabolic pathway such as purine metabolism, amino acid metabolism and tyrosine metabolism. These biomarkers showed different roles in disease development. CONCLUSION: Metabolomics was proved as a powerful tool in understanding the mechanism of recurrent abortion caused by APS.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31752069

RESUMO

In this study, the acidic lipase from Aspergillus niger (ANL) was homologously expressed in A. niger. The expression of ANL was significantly improved by the expression of the native ANL with the introns, the addition of the kozak sequence and the optimization of the signal sequences. When the cDNA sequence of ANL fused with the glaA signal was expressed under the gpdA promoter in A. niger, no lipase activity could be detected. Then we tried to improve the expression by using the full length ANL gene containing three introns, and the lipase activity in the supernatant reached 75.80 U/mL, which probably contributed by a more stable mRNA structure. The expression was further improved to 100.60 U/mL by introducing a kozak sequence around the start codon due to a higher translation efficiency. Finally, the effects of three signal sequences including the cbhI signal, the ANL signal and the glaA signal on the lipase expression were evaluated. The transformant with the cbhI signal showed the highest lipase activity (314.67 U/mL), which was 1.90 -fold and 3.13 -fold higher than those with ANL signal and glaA signal, respectively. The acidic lipase was characterized. Highest activity was detected at pH 3.0 and a temperature of 45°C. These results provided promising strategies for the production of the acidic lipase from A. niger.

7.
Nanomedicine ; 24: 102116, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31672602

RESUMO

Few studies reported the application of miRNA in bone regeneration. In this study, the expression of miR133a and miR133b in murine BMSCs was inhibited via antagomiR-133a/b and the osteogenic differentiation in murine BMSCs was evaluated. The RT-PCR, flow cytometry, cell counting kit-8, and annexin V-FITC/PI double staining assays were performed. Double knockdown miR133a and miR133b can promote BMSC osteogenic differentiation. At optimum N/P ration (15:1), the loading efficiency can reach over 90%. CTH-antagomiR-133a/b showed no cytotoxicity to BMSCs and diminished miR133a and miR133b expression in BMSCs. Furthermore, chitosan-based sustained delivery system can facilitate continuous dosing of antagomiR-133a/b, which enhanced calcium deposition and osteogenic specific gene expression in vitro. The new bone formation was enhanced after the sustained delivery system containing CTH-antagomiR-133a/b nanoparticles was used in mouse calvarial bone defect model. Our results demonstrate that CTH nanoparticles could facilitate continuous dosing of antagomiR133a/b, which can promote osteogenic differentiation.

8.
Int J Mol Sci ; 20(20)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623239

RESUMO

Light is one of the most important abiotic factors for most plants, which affects almost all growth and development stages. In this study, physiological indicators suggest that the application of exogenous Ca2+ improves photosynthesis and changes phytohormone levels. Under weak light, photosynthetic parameters of the net photosynthetic rate (PN), stomatal conductance (Gs), and transpiration rate (Tr) decreased; the antioxidation systems peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) reduced; the degrees of malondialdehyde (MDA), H2O2, and superoxide anion (O2-) free radical damage increased; while exogenous Ca2+ treatment was significantly improved. RNA-seq analysis indicated that a total of 13,640 differently expressed genes (DEGs) were identified and 97 key DEGs related to hormone, photosynthesis, and calcium regulation were differently transcribed. Gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses, plant hormone signal transduction, photosynthesis, carbon metabolism, and phenylpropanoid biosynthesis were significantly enriched. Additionally, quantitative real-time PCR (qRT-PCR) analysis confirmed some of the key gene functions in response to Ca2+. Overall, these results provide novel insights into the complexity of Ca2+ to relieve injuries under weak light, and they are helpful for potato cultivation under weak light stress.

9.
Free Radic Res ; 53(11-12): 1073-1083, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31631710

RESUMO

Of all the aerobic respiration by-products, cytotoxic superoxide derived from mitochondrial-leaked electrons, is the only one known to be disposed of intracellularly. Is this fate the only destiny for mitochondrial-leaked electrons? When Cynomolgus monkeys were injected intravenously with reactive oxygen species (ROS) indicators, the connective tissues of dura mater, facial fascia, pericardium, linea alba, dorsa fascia and other body parts, emitted specific and intense fluorescent signals. Moreover, the fluorescent signals along the linea alba of SD rats, did not result from the local presence of ROS but from the interaction of ROS indicators with electrons flowing through this tissue. Furthermore, the electrons travelling along the linea alba of mice were revealed to originate from mitochondria. These data suggest that mitochondrial-leaked electrons may be transported extracellularly to a hitherto undescribed system of connective tissues, which is pervasively networked, electrically conductive and metabolically related.

10.
Colloids Surf B Biointerfaces ; 184: 110501, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31541891

RESUMO

Supported cross-linked enzyme aggregates were prepared by immobilization of Candida antarctica lipase B onto hydrophobic surface of octyl-modified mesocellular foams (MCFs-C8). Oxidized sodium alginate was used as a substitute for traditional glutaraldehyde. Supported cross-linked enzyme aggregates using oxidized sodium alginate (SA-CLEAs@MCFs-C8) exhibited significantly improved thermal stability and organic solvents tolerance compared to the free lipase, lipase adsorbed onto MCFs-C8 and supported cross-linked enzyme aggregates using glutaraldehyde (G-CLEAs@MCFs-C8). Then immobilized lipases were employed for biodiesel production by transesterification of soybean oil with methanol. In the optimization condition, SA-CLEAs@MCFs-C8 were quite stable and still showed high fatty acid methyl esters (FAME) yield after 5 repeated cycles (from 89% to 78%), whereas MCFs-C8-CALB retained 67% FAME yield (about 72% for G-CLEAs@MCFs-C8).

11.
Biochemistry ; 58(38): 3943-3954, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31436959

RESUMO

Members of an important group of industrial enzymes, Rhizopus lipases, exhibit valuable hydrolytic features that underlie their biological functions. Particularly important is their N-terminal polypeptide segment (NTPS), which is required for secretion and proper folding but is removed in the process of enzyme maturation. A second common feature of this class of lipases is the α-helical "lid", which regulates the accessibility of the substrate to the enzyme active site. Some Rhizopus lipases also exhibit "interfacial activation" by micelle and/or aggregate surfaces. While it has long been recognized that the NTPS is critical for function, its dynamic features have frustrated efforts to characterize its structure by X-ray crystallography. Here, we combine nuclear magnetic resonance spectroscopy and X-ray crystallography to determine the structure and dynamics of Rhizopus chinensis lipase (RCL) with its 27-residue NTPS prosequence (r27RCL). Both r27RCL and the truncated mature form of RCL (mRCL) exhibit biphasic interfacial activation kinetics with p-nitrophenyl butyrate (pNPB). r27RCL exhibits a substrate binding affinity significantly lower than that of mRCL due to stabilization of the closed lid conformation by the NTPS. In contrast to previous predictions, the NTPS does not enhance lipase activity by increasing surface hydrophobicity but rather inhibits activity by forming conserved interactions with both the closed lid and the core protein structure. Single-site mutations and kinetic studies were used to confirm that the NTPS serves as internal competitive inhibitor and to develop a model of the associated process of interfacial activation. These structure-function studies provide the basis for engineering RCL lipases with enhanced catalytic activities.

12.
ACS Appl Mater Interfaces ; 11(37): 34416-34423, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31438669

RESUMO

Nonvacuum printing of single crystals would be ideal for high-performance functional device (such as electronics) fabrication yet challenging for most materials, especially for inorganic semiconductors. Currently, the printed films are dominant in amorphous, polycrystalline, or nanoparticle films. In this article, manufacturing of single-crystal silicon micro/nano-islands is attempted. Different from traditional vapor deposition for silicon thin-film preparation, silicon nanoparticle ink was aerosol-printed followed by confined laser melting and crystallization, allowing potential fabrication of single-crystal silicon micro/nano-islands. It is also shown that as-fabricated Si islands can be transfer-printed onto polymer substrates for potential application of flexible electronics. The additive nature of this technique suggests a scalable and economical approach for high-crystallinity semiconductor printing.

13.
Curr Ther Res Clin Exp ; 90: 99-105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31388362

RESUMO

Background: Amlodipine (AML) is the initial therapy most commonly prescribed for patients with hypertension in China. However, AML monotherapy is often less effective in achieving blood pressure (BP) control than other agents. Objective: We performed a clinical study to evaluate efficacy and safety of a combination therapy with AML, olmesartan (OLM), or an OLM/hydrochlorothiazide (HCTZ) compound for Chinese patients with mild-to-moderate hypertension. Methods: In the clinical trial, patients were initially treated with OLM 20 mg/d combined with AML 5 mg/d. Then OLM was uptitrated to 40 mg/d or changed to an OLM/HCTZ (20/12.5 mg/d) compound if the patients did not reach the target of seated diastolic BP <90 mm Hg (<80 mm Hg in patients with diabetes) after 8 weeks. Results: The overall response rate of the combination therapy was 59.2% (95% CI, 54.23%-63.97%) at Week 2 and gradually increased to 97.1% (95% CI, 94.93%-98.47%) at the end of the study (Week 16). Conclusions: The combination therapy with OLM or OLM/HCTZ was well tolerated. The total incidence of adverse events was 42.9% (n = 176). Most of the adverse events were mild in severity (39.5%; n = 162) and not associated with the drugs (33.2%). In conclusion, combination therapy with AML, OLM, or OLM/HCTZ can significantly lower BP safely and achieve a high BP control rate in patients with mild-to-moderate hypertension in China. ClinicalTrial.org identifier: ChiCTR-ONC-12001963.

14.
Organogenesis ; 15(2): 43-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31272281

RESUMO

Type 2 diabetes mellitus (T2DM) accounts for approximately 90% of all diabetic patients, and osteoporosis is one of the complications during T2DM process. ATP6V1H (V-type proton ATPase subunit H) displays crucial roles in inhibiting bone loss, but its role in osteogenic differentiation remains unknown. Therefore in this study, we aimed to explore the biological role of ATP6V1H in osteogenic differentiation. OM (osteogenic medium) and HG (high glucose and free fatty acids) were used to induce the MC3T3-E1 cells into osteogenic differentiation in a T2DM simulating environment. CCK8 assay was used to detect cell viability. Alizarin Red staining was used to detect the influence of ATP6V1H on osteogenic differentiation. ATP6V1H expression increased in OM-MC3T3-E1 cells, while decreased in OM+HG-MC3T3-E1 cells. ATP6V1H promoted osteogenic differentiation of OM+HG-MC3T3-E1 cells. Overexpression of ATP6V1H inhibited Akt/GSK3ß signaling pathway, while knockdown of ATP6V1H promoted Akt/GSK3ß signaling pathway. ATP6V1H overexpression promoted osteogenic differentiation of OM+HG-MC3T3-E1 cells. The role of ATP6V1H in osteogenic differentiation in a T2DM simulating environment involved in Akt/GSK3ß signaling pathway. These data demonstrated that ATP6V1H could serve as a potential target for osteogenic differentiation in a T2DM simulating environment.

15.
Nutr Res ; 67: 1-16, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078816

RESUMO

As an endocrine disruptor, tyrosine kinase inhibitor, and DNA methyltransferase inhibitor, genistein can interfere with breast cancer development. However, as the results of numerous studies are contradictory, it is unclear whether genistein plays a positive or negative role. Retrospective epidemiological studies have indicated that high genistein intake is related to reduced breast cancer risk, but this protective effect has not been reported in clinical trials. Additionally, rodent and cellular studies show that genistein promoted breast cancer progression. Obviously, genistein's bioactivities do not solely depend upon the dose, and simply discussing the overall effects of genistein without considering individual factors is unrealistic. The purpose of this review was to collect relevant studies (over 164) on genistein and breast cancer that were published on PubMed from 1984 to 2019 and to summarize the impact of key individual factors on the bioactivities of genistein in breast cancer prevention and treatment. Furthermore, the related potential molecular mechanisms were explored to explain the contradictions in genistein-breast cancer studies. Our results showed that the intake mode and metabolic characteristics of genistein, as well as the menopausal status, estrogen receptor expression pattern, and gene mutations of the patient, are important factors that should be included when discussing the bioactivities of genistein. A better understanding of the influence of individual factors may enable the precise prediction of personalized responses to dietary genistein exposure. Given that the current information on genistein is mostly restricted to the cellular level, more comprehensive human studies should be performed to clarify the relationship between genistein and breast cancer.

16.
Pak J Med Sci ; 35(2): 549-554, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31086549

RESUMO

Objective: To explore the relationships between expression of CD44v6, lymphatic vessel density (LVD) and the clinicopathological parameters of patients. Methods: One hundred early gastric cancer tissues, 55 high-grade gastric intraepithelial neoplasia (HGIN) tissues, 60 low-grade gastric intraepithelial neoplasia (LGIN) tissues and 60 chronic superficial gastritis tissues were collected and set as gastric cancer group, HGIN group, LGIN group and gastritis group respectively. The expression of CD44v6 and LVD of patients in all the groups were detected using two-step immunohistochemical method to analyze the relationships between the expression of CD44v6 and lymphatic vessel density in early gastric cancer tissues and their relationships with the clinicopathological parameters of patients. The values of LVD in predicting lymph node metastasis in early gastric cancer were evaluated using receiver operating characteristic (ROC) curve. Results: The positive expression of CD44v6 and LVD in the gastritis group, LGIN group, HGIN group and gastric cancer group gradually increased. The positive expression of CD44v6 and LVD in early gastric cancer tissues were in no correlation with the gender, age, tumor site, maximum diameter, differentiation degree and invasion depth (P>0.05) and in a correlation with lymphatic metastasis and lymphatic vessel invasion (P<0.06). The positive expression of CD44v6 in the early gastric cancer tissues was in a positive correlation with LVD (P<0.05). The analysis of ROC curves suggested that the area under ROC curve of predicting lymphatic metastasis of early gastric cancer with LVD was 0.837 (95% CI: 0.756~0.910), and the cut-off value was 14; the corresponding sensitivity and specificity were 63.6% and 90.2 respectively. Conclusion: The expression of CD44v6 and LVD in early gastric cancer tissues are in a close correlation with the clinicopathologic features, and joint detection of expression of CD44v6 and LVD can be taken as the indicator of gastric cancer metastasis.

17.
Huan Jing Ke Xue ; 40(4): 1553-1561, 2019 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087895

RESUMO

To investigate the characteristics, sources, and health risks of trace heavy metals in fine particles, PM2.5 samples were collected at a suburban site of Zhuhai in the Pearl River Delta Region. Fifteen elements in the PM2.5 were analyzed by an X-ray fluorescence method. The results showed that the total mass concentrations of crustal elements (Al, Si, Ca, Fe, and Ti) in a typical month during spring, summer, autumn, and winter were (708±213), (645±269), (1155±503), and (1466±492) ng·m-3, respectively, while the total mass concentrations of the rest of the trace elements (Ba, Co, Cr, Cu, Mn, Ni, Pb, Sb, V, and Zn) were (271±124), (163±87.6), (424±192), and (546±183) ng·m-3, respectively. The element concentrations decreased in the following order:Si > Al > Fe > Zn > Ca > Pb > Ba > Mn > Sb > Cu > Ti > V > Ni > Cr > Co. Enrichment factors (EFs) analysis showed that Sb, Zn, Pb, Cu, Ni, Ba, Ca, and Co were heavily enriched, with EFs values ranging from 172 to 2426. Principal component analysis further showed that regional transport, ship emissions, coal combustion, and the electronics industry were the major sources of heavy metals, contributing 53.4%, 13%, 7.6%, and 6.8% of the total, respectively. Health risk assessment results indicated that Mn may pose a non-carcinogenic risk to children, and Cr, Pb, and Co may pose cancer risks to humans.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Metais Pesados/efeitos adversos , Medição de Risco , Poluentes Atmosféricos/análise , Cidades , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Material Particulado/efeitos adversos , Material Particulado/análise
18.
Int J Biol Macromol ; 130: 342-347, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30825565

RESUMO

Lipase r27RCL from Rhizopus chinensis was immobilized onto octyl-modified mesocellular foams (MCFs-C8) via two-step process of enzyme adsorption and cross-linking. Oxidized gum arabic was used as substitute for harmful glutaraldehyde to improve catalytic performance of immobilized enzyme for catalysis in non-aqueous phase. The parameters like aldehyde concentration, cross-linking time were optimized. Cross-linked enzyme aggregates (CLEAs) of lipase r27RCL prepared in MCFs-C8 by using oxidized gum arabic (GA-CLEAs@MCFs-C8) showed the highest esterification activity (145 µmol min-1 mg-1 protein) compared with lipase adsorbed onto MCFs-C8 (MCFs-C8-r27RCL) (98 µmol min-1 mg-1 protein), CLEAs of lipase in MCFs-C8 by glutaraldehyde (G-CLEAs@MCFs-C8) (88 µmol min-1 mg-1 protein) and immobilized lipase onto octyl/epoxy (1,1, v/v) modified MCFs (MCFs-octyl-epoxy-r27RCL) (35 µmol min-1 mg-1 protein). Moreover, GA-CLEAs@MCFs-C8 exhibited excellent thermal and mechanical stability, and could still maintain 69% of initial activity after 5 time cycles.


Assuntos
Enzimas Imobilizadas/química , Lipase/química , Agregados Proteicos , Rhizopus/enzimologia , Adsorção , Biocatálise , Enzimas Imobilizadas/metabolismo , Esterificação , Goma Arábica/química , Lipase/metabolismo , Fenômenos Mecânicos , Oxirredução , Temperatura Ambiente
19.
Mol Cell Biochem ; 456(1-2): 205-216, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30737644

RESUMO

As one of the typical food-derived phytoestrogens, genistein (GEN) could bind to estrogen receptor (ER) and was reported to be closely related to breast cancer. Our former research showed that GEN interfered with the anti-tumor effects of cisplatin (CIS) in breast cancer MCF-7 (ERα+/ERß-) cells. However, it is not clear whether ER expression pattern affects GEN's modulation on CIS's activity. In the present study, breast cancer ERß knockdown (ERßKD) MDA-MB-231 (ERα-/ERß+) cell model was established via ERß RNAi lentivirus infection. The role of ERß expression in GEN's bioeffects on cells' response to CIS was investigated and was further double-checked by pathway-specific inhibitor PHTPP. Consistent results were harvested through cell viability analysis, cell cycle distribution flow cytometry, TUNEL staining, and expression detection of key biomarkers, Bax, Bcl-2, P21, P53, and cleaved caspase-3. Compared with the control group, PHTPP-treated or ERßKD cells exhibited higher sensitivity to both GEN and CIS treatment. GEN and CIS showed synergistic effects only in ERß-deficient cells. This effect mainly resulted in G2 phase arresting and apoptosis induction with the upregulation of P21 and Bax/Bcl-2 protein level. Besides, P53 expression was strikingly suppressed in ERß-deficient cells. This indicated ERß pathway deficiency might enhance GEN-CIS bioactivity via the downregulation of P53. In summary, our data imply that daily intake of GEN-rich diet could collaborate with CIS anti-tumor treatment in ERα-/ERß- breast cancer cases. ERß pathway might be one of the potential targets which elicit GEN's positive effects in ERα- breast cancer patients.


Assuntos
Neoplasias da Mama/metabolismo , Cisplatino/farmacologia , Receptor beta de Estrogênio/metabolismo , Genisteína/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Receptor beta de Estrogênio/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
20.
Int Immunol ; 31(4): 263-273, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30779845

RESUMO

Inflammation plays an important role in osteonecrosis. Obesity, a risk factor for osteonecrosis, leads to a chronic inflammatory status. We hypothesized that inflammation mediated the effects of obesity on osteonecrosis and tested our hypothesis in a mouse model of osteonecrosis. We fed mice with a high-fat diet (HFD) for 12 weeks before osteonecrosis induction by methylprednisolone and examined bone structure and IL-6 expression. Then we investigated the effects of IL-6 deletion in mice with osteonecrosis on the HFD. Next, we isolated bone marrow cells and determined the cell types responsible for HFD-induced IL-6 secretion. Finally, we investigated the roles of macrophages and macrophage-driven IL-6 in HFD-mediated effects on osteonecrosis and osteogenesis of bone marrow stromal cells (BMSCs). The HFD lead to exacerbated destruction of the femoral head in mice with osteonecrosis and increased IL-6 expression in macrophages. Il-6 knockout or macrophage depletion suppressed the effects of the HFD on bone damage. When co-cultured with macrophages isolated from HFD-fed mice with osteonecrosis, BMSCs showed reduced viability and suppressed osteogenic differentiation. Our results suggest that macrophage-driven IL-6 bridges obesity and osteonecrosis and inhibition of IL-6 or depletion of macrophage may represent a therapeutic strategy for obesity-associated osteonecrosis.

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