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1.
Food Chem ; 302: 125275, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31442701

RESUMO

2,6-Dimethoxy-ρ-benzoquinone (DMBQ) is a potential anti-tumor substance found in the fermented wheat germ. In this study, ultrasound and Fe3O4 nanoparticles were used to improve the DMBQ yield. An artificial neural network (ANN) embedded separately with the back-propagation algorithm (BP), genetic algorithm (GA), particle swarm optimized algorithm (PSO), ant colony optimized algorithm (ACO), GA-ACO, GA-PSO and PSO-ACO, were used to establish the relationship between 11 factors and DMBQ yield. The robustness and generalization of PSO-ACO-ANN, which gave the minimum mean squared error and mean absolute percentage error for the training and test dataset, was superior to the others. Next, a modified Garson's algorithm and mixed partial derivatives algorithm indicated that the most influential paired-parameters were ultrasonic power and concentration of nanoparticles. Finally, the factors were optimized by six optimization algorithms, and confirmatory experimental results indicated that the optimum DMBQ yield was 0.213 ±â€¯0.007 mg/g, which was 161.2% higher than the control.

2.
J Nanosci Nanotechnol ; 20(2): 692-700, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383064

RESUMO

Fluorescent bimetallic Au-Ag nanoclusters (Au-AgNCs) were found to exhibit oxidase-like activity and could catalyze the oxidation of 3,3',5,5' tetramethylbenzidine (TMB) to oxTMB. On the basis of this property, we assembled a fluorescent nanoplatform as a turn-on probe for sensing mercury (II) ions (Hg2+) through the inner-filter effect (IFE). Au-AgNCs and oxTMB were chosen as IFE absorber and fluorophore pair for the first time. In the absence of Hg2+, the Au-AgNCs absorption band well. Covered the fluorescence emission band of oxTMB, and as a result, the fluorescence of oxTMB was reduced. In the presence of Hg2+, Hg2+ was reduced to Hg0 by extra BSA in Au-AgNCs probe system and anchored on the surface of Au-AgNCs. The absorption intensity for Au-AgNCs then decreased at 418 nm, resulting in the recovery of fluorescence from oxTMB. The formed Au-Hg thin amalgam layer obviously enhanced the oxidase-like activity of Au-AgNCs as well as hindered the IFE activity between Au-AgNCs and oxTMB. Therefore, based on the Hg2+ stimulating oxidaselike properties of Au-AgNCs, a fluorometric assay for determination of Hg2+ was developed in this study. The proposed sensing strategy showed a linear range from 10 nM to 500 nM, with ultralow LOD of ~0.7 nM for Hg2+. Moreover, the detection probe system was stable over a wide pH range, making it able to be applied in complex sample systems. We have successfully demonstrated the detection of Hg2+ in tap water samples. The fluorescent assay reported here, for sensitive and selective determination of Hg2+, may find great application in multiple areas, such as environmental and pharmaceutical analysis.

3.
Anal Chem ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31476117

RESUMO

Kinases, which function in numerous cell signaling processes, are among the best characterized groups of client proteins for the 90-kDa heat shock protein (HSP90), a molecular chaperone that suppresses the aggregation and maintains the proper folding of its substrate proteins (i.e., clients). No high-throughput proteomic method, however, has been developed for the characterizations of the interactions between HSP90 and the human kinome. Herein, by employing a parallel-reaction monitoring (PRM)-based targeted proteomic method, we found that 99 out of the 249 detected kinase proteins display diminished expression in cultured human cells upon treatment with ganetespib, a small-molecule HSP90 inhibitor. PRM analysis of kinase proteins in the affinity pull-down samples showed that 86 out of the 120 detected kinases are enriched from the CRISPR-engineered cells where a tandem affinity tag was conjugated with the C-terminus of endogenous HSP90ß protein over the parental cells. Together, our results from the two complementary quantitative proteomic experiments offer systematic characterizations about the HSP90-kinase interactions at the entire proteome scale and reveal extensive interactions between HSP90 and kinase proteins in human cells.

4.
Plant Cell ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484683

RESUMO

Plant surface waxes form an outer barrier that protects the plant from many forms of environmental stress. The deposition of cuticular waxes on the plant surface is regulated by external environmental changes, including light and dark cycles. However, the underlying molecular mechanisms controlling light regulation of wax production is are still poorly understood, especially at the post-transcriptional level. In this paper, we report the regulation of cuticular wax production by the miR156-SPL9 module in Arabidopsis. Compared with wild-type plants, miR156 and SPL9 mutants showed significantly altered cuticular wax amounts in both stems and leaves. Furthermore, it was found that SPL9 positively regulates gene expression of the alkane-forming enzyme CER1, as well as the primary (1-) alcohol-forming enzyme CER4, to enhance alkane and 1-alcohol synthesis respectively. More importantly, our results indicate that complex formation of SPL9 with a negative regulator of wax synthesis, DEWAX, will hamper SPL9 DNA binding ability, possibly by interfering with SPL9 homodimerization. Combined with their diurnal gene and protein expressions, this dynamic repression-activation transcriptional module defines a dynamic mechanism that may allow plants to optimize wax synthesis during daily cycles. These findings provide a regulatory framework for environmental signal integration in the regulation of wax synthesis.

5.
ACS Nano ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478375

RESUMO

The discovery in 1974 of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is considered a landmark in the history of spectroscopic and analytical techniques. Much experimental and theoretical effort has been spent toward understanding the surface enhanced Raman scattering (SERS) effect, and demonstrating its potential toward various types of ultrasensitive sensing applications in a wide variety of fields. Forty five years later, SERS has blossomed as an extremely rich area of research and technology, but additional efforts are still needed before it can be routinely used as a commercial product. In this Review, prominent authors from all over the world joined efforts to summarize the current state-of-the-art in understanding and using SERS, as well as to propose what can be expected in the near future, in terms of research, applications, and technological development.

6.
Sensors (Basel) ; 19(17)2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31480745

RESUMO

Recent developments in laser scanning systems have inspired substantial interest in indoor modeling. Semantically rich indoor models are required in many fields. Despite the rapid development of 3D indoor reconstruction methods for building interiors from point clouds, the indoor reconstruction of multi-room environments with curved walls is still not resolved. This study proposed a novel straight and curved line tracking method followed by a straight line test. Robust parameters are used, and a novel straight line regularization method is achieved using constrained least squares. The method constructs a cell complex with both straight lines and curved lines, and the indoor reconstruction is transformed into a labeling problem that is solved based on a novel Markov Random Field formulation. The optimal labeling is found by minimizing an energy function by applying a minimum graph cut approach. Detailed experiments were conducted, and the results indicate that the proposed method is well suited for 3D indoor modeling in multi-room indoor environments with curved walls.

7.
Cell Res ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481760

RESUMO

Breast cancer is a heterogeneous disease. In particular, triple-negative breast cancer (TNBC) comprises various molecular subgroups with unclear identities and currently has few targeted treatment options. Our previous study identified protein C receptor (Procr) as a surface marker on mammary stem cells (MaSCs) located in the basal layer of the normal mammary gland. Given the possible connection of TNBC with basal layer stem cells, we conducted comparative analyses of Procr in breast cancers of mouse and human origin. In mouse mammary tumors, we showed that Procr+ cells are enriched for cancer stem cells (CSCs) in Wnt1 basal-like tumors, but not in Brca1 basal-like tumors or PyVT luminal tumors. In human cancers, PROCR was robustly expressed in half of TNBC cases. Experiments with patient-derived xenografts (PDXs) revealed that PROCR marks CSCs in this discrete subgroup (referred to as PROCR+ TNBC). Interfering with the function of PROCR using an inhibitory nanobody reduced the CSC numbers, arrested tumor growth and prevented rapid tumor recurrence. Our data suggest a key role of MaSC in breast tumorigenesis. Moreover, our work indicates that PROCR can be used as a biomarker to stratify TNBC into clinically relevant subgroups and may provide a novel targeted treatment strategy for this clinically important tumor subtype.

8.
Adv Mater ; : e1902791, 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31496027

RESUMO

Protein/antibody therapeutics have exhibited the advantages of high specificity and activity even at an extremely low concentration compared to small molecule drugs. However, they are accompanied by unfavorable physicochemical properties such as fragile tertiary structure, large molecular size, and poor penetration of the membrane, and thus the clinical use of protein drugs is hindered by inefficient delivery of proteins into the host cells. To overcome the challenges associated with protein therapeutics and enhance their biopharmaceutical applications, various protein-loaded nanocarriers with desired functions, such as lipid nanocapsules, polymeric nanoparticles, inorganic nanoparticles, and peptides, are developed. In this review, the different strategies for intracellular delivery of proteins are comprehensively summarized. Their designed routes, mechanisms of action, and potential therapeutics in live cells or in vivo are discussed in detail. Furthermore, the perspective on the new generation of delivery systems toward the emerging area of protein-based therapeutics is presented as well.

9.
Health Commun ; : 1-10, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31496292

RESUMO

Health information technology (health IT) has the potential to facilitate the self-regulation of fruit and vegetable intake (FVI) and physical activity (PA). This study explores whether using health IT for self-regulation mediates the relationship between sociodemographic factors and health behaviors including FVI and PA among U.S. adults. Bayesian mediation analysis was used to analyze a nationally representative sample of the U.S. adults (N = 3285) from Cycle 1 of the 2017 Health Information National Trends Survey (HINTS). The 95% credibility intervals (CI) were calculated for each sociodemographic factor and the mediator using health IT for self-regulation in relation to FVI and PA. About 58% of the participants used at least one type of health IT for self-regulation. Age was negatively associated with using health IT for self-regulation, whereas being a female and having a higher income and education were positively associated with it. Using health IT for self-regulation partially mediated the positive relationships between income, education, and FVI, but it is unrelated to PA. The findings support the efficacy of using health IT to regulate healthier eating. Nevertheless, the digital divide is a critical issue to consider when applying health IT to promote behavior change.

10.
Med Sci Monit ; 25: 6775-6781, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31496537

RESUMO

BACKGROUND High-intensity focused ultrasound (HIFU) and plasma radiofrequency ablation (PRA) have been used to treat recurrent allergic rhinitis (AR); however, there is a lack of literature comparing the efficacy of these 2 methods. We assessed and compared the therapeutic effects of HIFU and PRA on recurrent AR. MATERIAL AND METHODS We enrolled 66 patients with recurrent AR at West China Hospital of Sichuan University. Visual analogue score (VAS), pain score, rhinoconjunctivitis quality of life questionnaire (RQLQ), and nasal endoscopy were performed to evaluate the therapeutic effect. RESULTS Nasal endoscopy showed that HIFU and PAR reduced the volume of the inferior turbinate, whereas HIFU reduced the amount of nasal secretions in patients. VAS scores showed that HIFU and PRA nasal congestion symptoms were significantly reduced (P<0.05). The preoperative VAS scores for nasal fluid and sneezing were significantly lower in patients receiving HIFU (P<0.05) than in those receiving PRA (P>0.05). HIFU-treated patients had significantly lower postoperative pain scores than those in the PRA group (P<0.05). RQLQ showed activity, sleep, and non-nasal or ocular symptoms, and both HIFU and PRA patients had significantly lower scores (P<0.05). Nasal symptom scores, actual problems, and mood in the HIFU group were significantly worse than those in the PRA group (P<0.05). However, neither treatment had a significant effect on ocular symptoms (P>0.05). CONCLUSIONS Compared with PRA, HIFU can significantly reduce the nasal symptoms of AR patients, improve the quality of life, and can be used as an adjuvant therapy with better therapeutic effect.

11.
Mikrochim Acta ; 186(9): 665, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478114

RESUMO

An amino-functionalized ordered mesoporous polymer (OMP-NH2) was synthesized and applied as a fiber coating for solid phase microextraction of polar phenols from environmental samples. The fiber coating was prepared by loading the OMP-NH2 powder onto a stainless steel wire through silicone gel. Combined with GC-MS, the fibers were employed to quantify trace of phenols in water through headspace-SPME. The characterization showed the OMP-NH2 to have a large specific surface area (420 m2 g-1) and good thermal stability (>400 °C). Due to its mesoporous structure and favorable interactions via hydrogen bonding and π stacking interactions with phenols, the sorbent represents a promising candidate for the separation and enrichment of polar phenols. Extraction conditions, such as temperature, extraction time, salt concentration, pH value and desorption time, were fully optimized. Under the optimized conditions, the coating exhibits an enrichment effect that is ~2-10 times better than that of a commercial polyacrylate coating. Figures of merit include (a) low limits of detection (0.05-0.16 ng L-1), (b) wide linear ranges (0.2-10,000 ng L-1), and (c) high enrichment factors (510-2272). The relative standard deviations for one fiber and fiber-to-fiber were in the range of 4.0-6.1% and 4.6-7.4%, respectively. The method was applied to the determination of phenols in water samples and gave satisfactory recoveries between 85.4 and 112.2%. Graphical abstract An amino-functionalized ordered mesoporous polymer (OMP-NH2) was synthesized by a solventless method and applied as headspace solid phase microextraction (HS-SPME) fiber coating for the extraction of polar phenols from the environmental samples.

12.
Sci Rep ; 9(1): 13062, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506551

RESUMO

The conventional electrowetting lens usually has one tunable liquid-liquid (L-L) interface. The shape of L-L interface is deformed to get variable focal length due to electrowetting effect. However, contact angle saturation of the L-L interface is an unavoidable problem which prevents focal length from further changing. Here, we demonstrate an optofluidic lens based on electrowetting liquid piston. The proposed lens has two connected chambers, the piston chamber and the lens chamber to form a closed-loop fluidic system. The electrowetting liquid piston can generate clockwise and counter-clockwise liquid flows, which can make the L-L interface convex and concave. To prove the concept, we fabricate an optofluidic device whose shortest negative and positive focal lengths are ~-17.9 mm and ~18 mm with 5 mm aperture, respectively. The proposed optofluidic lens has large tunable focal length range. Widespread application of such an adaptive lens is foreseeable.

13.
Eur J Pharmacol ; 862: 172637, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31491402

RESUMO

To support proliferation, tumour cells often undergo a metabolic switch to aerobic glycolysis, and a large amount of fatty acids (FAs) is produced to provide conditions for the formation of cell membrane structures. This phenomenon is particularly prominent in clear cell renal cell carcinoma (ccRCC). FAs need to be combined with fatty acid binding proteins (FABPs) for transport. Fatty Acid Binding Protein 5 (FABP5) is an important chaperone protein of FAs that is upregulated in a variety of tumours. However, to date, the potential regulatory role and molecular mechanisms of FABP5 in the development and progression of cancers, including ccRCC, remain unknown. Herein, we demonstrate that FABP5 is upregulated in human ccRCC tissues and cell lines and is positively correlated with the progression of ccRCC. FABP5 deletion inhibits the proliferation, colony-forming ability and migration of ccRCC cells, suggesting that FABP5 may be a cancer-promoting protein in ccRCC. Mechanistically, FABP5 deletion significantly downregulated MMP9 and the transcription factor Snail1 in addition to upregulating E-cadherin and downregulating N-cadherin and Vimentin to inhibit epithelial-mesenchymal transition (EMT) in the ACHN cell line. In summary, our data suggest that FABP5 may be a potential therapeutic target in ccRCC.

14.
Mater Sci Eng C Mater Biol Appl ; 104: 109961, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500022

RESUMO

Formation of fungal biofilms on health care-related materials causes serious clinical consequences. This study reports a novel fungal repelling strategy to control fungal biofilm formation on denture biomaterials through layer-by-layer self-assembly (LBL). Amphiphilic quaternary ammonium chitosans (CS612) were synthesized and used as the antimicrobial positive layer, and sodium alginate (SA) was chosen as the negative layer to construct LBL multilayers on poly (methyl methacrylate) (PMMA)-based denture materials. The presence of LBL multilayers on denture disc was confirmed and characterized by surface zeta potential, water contact angle, AFM, and FT-IR analyses. The multilayer coatings, especially CS612 as the outmost layer, effectively prevented the fungal initial adhesion and biofilm formation. The Candida cells avoided the multilayer coatings and suspended in broth solution instead of forming biofilms, suggesting that the LBL multilayers had fungal repelling effects. The LBL multilayers were biocompatible toward mammalian cells. In stability tests, after immersion in PBS for 4 weeks under constant shaking and repeated brushing with a denture brush for up to 3000 times, the biofilm-controlling effects of the LBL multilayers were not affected, pointing to a novel long-term strategy in controlling fungal biofilms on denture and other related biomaterials.

15.
Cell Res ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501519

RESUMO

The response of endothelial cells to signaling stimulation is critical for vascular morphogenesis, homeostasis and function. Vascular endothelial growth factor-a (VEGFA) has been commonly recognized as a pro-angiogenic factor in vertebrate developmental, physiological and pathological conditions for decades. Here we report a novel finding that genetic ablation of CDP-diacylglycerol synthetase-2 (CDS2), a metabolic enzyme that controls phosphoinositide recycling, switches the output of VEGFA signaling from promoting angiogenesis to unexpectedly inducing vessel regression. Live imaging analysis uncovered the presence of reverse migration of the angiogenic endothelium in cds2 mutant zebrafish upon VEGFA stimulation, and endothelium regression also occurred in postnatal retina and implanted tumor models in mice. In tumor models, CDS2 deficiency enhanced the level of tumor-secreted VEGFA, which in-turn trapped tumors into a VEGFA-induced vessel regression situation, leading to suppression of tumor growth. Mechanistically, VEGFA stimulation reduced phosphatidylinositol (4,5)-bisphosphate (PIP2) availability in the absence of CDS2-controlled-phosphoinositide metabolism, subsequently causing phosphatidylinositol (3,4,5)-triphosphate (PIP3) deficiency and FOXO1 activation to trigger regression of CDS2-null endothelium. Thus, our data indicate that the effect of VEGFA on vasculature is context-dependent and can be converted from angiogenesis to vascular regression.

16.
BMC Cancer ; 19(1): 882, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488104

RESUMO

BACKGROUND: Bispecific T-cell engaging antibodies (BiTES), comprising dual anti-CD3 and anti-tumor antigen scFv fragments, are important therapeutic agents for the treatment of cancer. The dual scFv construct for BiTES requires proper protein folding while their small molecular size leads to rapid kidney clearance. METHODS: An intact (150 kDa) anti-tumor antigen antibody to CEA was joined in high yield (ca. 30%) to intact (150 kDa) anti-murine and anti-human CD3 antibodies using hinge region specific Click chemistry to form dual-specific, bivalent BiTES (dbBiTES, 300 kDa). dbBiTEs were tested in vitro by EM, flow cytometry and cell cytoxicity and in vivo by PET tumor imaging and redirected T-cell therapy. RESULTS: The interlocked hinge regions are compatible with a structural model that fits the electron micrographs of 300 kDa particles. Compared to intact anti-CEA antibody, dbBiTES exhibit high in vitro cytotoxicity, high in vivo tumor targeting as demonstrated by PET imaging, and redirected dbBiTE coated T-cells (1 microgram/10 million cells) that kill CEA+ target cells in vivo in CEA transgenic mice. CONCLUSION: dbBiTE redirected T-cell therapy is a promising, efficient approach for targeting and killing cancer cells.

17.
J Control Release ; 311-312: 104-116, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484040

RESUMO

Currently, most anti-cancer therapies are still haunted by serious and deleterious adverse effects. Here, we report a highly biocompatible tumor cell-targeting delivery systems utilizing exosome-like vesicles (ELVs) that delivers a low-toxicity anti-cancer agent imperialine against non-small cell lung cancer (NSCLC). First, we introduced a novel micelle-aided method to efficiently load imperialine into intact ELVs. Then, integrin α3ß1-binding octapeptide cNGQGEQc was modified onto ELV platform for tumor targeting as integrin α3ß1 is overexpressed on NSCLC cells. This system not only significantly improved imperialine tumor accumulation and retention, but also had extremely low systemic toxicity both in vitro and in vivo. Our discoveries offer new ways to utilize ELV more efficiently for both drug loading and targeting. The solid pharmacokinetics improvement and extraordinary safety of this system also highlight possibilities of alternative long course cancer therapies using similar strategies.

18.
Biomed Res Int ; 2019: 5701236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380431

RESUMO

Purpose: Ocular Response Analyzer (ORA) is one of the most widely used devices in clinic, while the mechanical interpretations of parameters obtained from ORA have not been understood completely. The aim of this research is to explore the mechanical interpretation of ORA parameters. Methods: Rabbits aged 3-24 months were measured with ORA in vivo and corneal strips uniaxial tensile tests to get ORA parameters and corneal biomechanical parameters (corneal elastic modulus, relaxation time, and relaxation limit). The mechanical interpretation of ORA parameters was cognized preliminarily by analyzing the correlation between ORA parameters and corneal biomechanical parameters. On the other hand, finite element method was applied to simulate ORA measurements with different corneal biomechanical parameters to obtain quantitative relationship between ORA parameters and corneal biomechanical parameters further. Results: Biomechanical experimental results showed that Corneal Resistance Factor (CRF) was correlated with corneal elastic modulus and relaxation limit significantly, while the significant correlations between Corneal Hysteresis (CH) and corneal biomechanical parameters were not observed. Results of finite element analysis showed that both CH and CRF were correlated with corneal elastic modulus, relaxation limit, and relaxation time significantly. Besides, corneal elastic modulus was positively correlated with upslop1 and upslop2 and negatively correlated with w2. Conclusions: For all ORA parameters, CH, CRF, the upslope, and the width of the peaks are parameters which may reflect corneal elastic properties. It is viable to cognize mechanical interpretation of ORA parameters by the comparisons of the data from ORA and biomechanical tests of rabbits with different ages and the simulations of ORA based on finite element methods. Further studies are needed to confirm the mechanical interpretation.

19.
Anatol J Cardiol ; 22(2): 68-76, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31375651

RESUMO

OBJECTIVE: It is unknown whether the intravascular ultrasound (IVUS) guidance for percutaneous coronary intervention (PCI) should be routinely used in small-vessel coronary lesions in patients affected by Type 2 diabetes mellitus (T2DM). This study aimed to assess the clinical significance of the IVUS-guided PCI treatment for small-vessel coronary lesions in T2DM. METHODS: This was a prospective interventional trial. A total of 228 patients affected by T2DM with stable angina and a positive stress test in the presence of coronary arteriography (CAG) involving small vessels [online measurement reference vessel diameter ≤3.0 mm by means of quantitative coronary angiography (QCA)] were recruited and divided into two groups: an IVUS-guided group (n=120) and a CAG-guided group (n=108). Follow-up PCIs were performed via CAG or IVUS criteria, respectively. Between-group comparisons were made for the number of stents implanted, length, diameter, and high-pressure balloons used post-dilatation. Major adverse cardiac events (MACEs) defined as cardiac death, nonfatal myocardial infarction, and target lesion revascularization (TLR) were the primary endpoint. The value of late lumen loss and proportion of in-stent restenosis (ISR) were the secondary endpoint, all of which were also evaluated during the follow-up period. RESULTS: There was an increased lesion length observed using the IVUS measurement when compared with QCA measurements in the IVUS-guided group (p≤0.001). The number of implanted stents, diameter, length, percentage of high-pressure balloons used during post-dilatation, value of late lumen loss, and proportion of ISR decreased in the IVUS-guided group when compared with the CAG-guided group (p=0.002, p=0.001, p=0.003, p=0.004, p=0.007, p=0.001, respectively). After a 2-year follow-up, the Kaplan-Meier curves indicated that the incidence of MACEs was significantly lower in the IVUS-guided group (log-rank p=0.029), mainly because of the TLR reduction (log-rank p=0.037). CONCLUSION: The IVUS-guided PCI treatment improved the event-free survival in small-vessel coronary lesions in patients affected by T2DM.

20.
Mol Cell ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31420216

RESUMO

The mitochondrial pathway of apoptosis is controlled by the ratio of anti- and pro-apoptotic members of the Bcl-2 family of proteins. The molecular events underlying how a given physiological stimulus changes this ratio to trigger apoptosis remains unclear. We report here that human 17-ß-estradiol (E2) and its related steroid hormones induce apoptosis by binding directly to phosphodiesterase 3A, which in turn recruits and stabilizes an otherwise fast-turnover protein Schlafen 12 (SLFN12). The elevated SLFN12 binds to ribosomes to exclude the recruitment of signal recognition particles (SRPs), thereby blocking the continuous protein translation occurring on the endoplasmic reticulum of E2-treated cells. These proteins include Bcl-2 and Mcl-1, whose ensuing decrease triggers apoptosis. The SLFN12 protein and an apoptosis activation marker were co-localized in syncytiotrophoblast of human placentas, where levels of estrogen-related hormones are high, and dynamic cell turnover by apoptosis is critical for successful implantation and placenta development.

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