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1.
Eur Radiol ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31485837

RESUMO

OBJECTIVE: To investigate the natural history of persistent pulmonary pure ground-glass nodules (pGGNs) with deep learning-assisted nodule segmentation. METHODS: Between January 2007 and October 2018, 110 pGGNs from 110 patients with 573 follow-up CT scans were included in this retrospective study. pGGN automatic segmentation was performed on initial and all follow-up CT scans using the Dr. Wise system based on convolution neural networks. Subsequently, pGGN diameter, density, volume, mass, volume doubling time (VDT), and mass doubling time (MDT) were calculated automatically. Enrolled pGGNs were categorized into growth, 52 (47.3%), and non-growth, 58 (52.7%), groups according to volume growth. Kaplan-Meier analyses with the log-rank test and Cox proportional hazards regression analysis were conducted to analyze the cumulative percentages of pGGN growth and identify risk factors for growth. RESULTS: The mean follow-up period of the enrolled pGGNs was 48.7 ± 23.8 months. The median VDT of the 52 pGGNs having grown was 1448 (range, 339-8640) days, and their median MDT was 1332 (range, 290-38,912) days. The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p < 0.001). The growth pattern of pGGNs may conform to the exponential model. Lobulated sign (p = 0.044), initial mean diameter (p < 0.001), volume (p = 0.003), and mass (p = 0.023) predicted pGGN growth. CONCLUSIONS: Persistent pGGNs showed an indolent course. Deep learning can assist in accurately elucidating the natural history of pGGNs. pGGNs with lobulated sign and larger initial diameter, volume, and mass are more likely to grow. KEY POINTS: • The pure ground-glass nodule (pGGN) segmentation accuracy of the Dr. Wise system based on convolution neural networks (CNNs) was 96.5% (573/594). • The median volume doubling time (VDT) of 52 pure ground-glass nodules (pGGNs) having grown was 1448 days (range, 339-8640 days), and their median mass doubling time (MDT) was 1332 days (range, 290-38,912 days). The mean time to growth in volume was 854 ± 675 days (range, 116-2856 days). • The 12-month, 24.7-month, and 60.8-month cumulative percentages of pGGN growth were 10%, 25.5%, and 51.1%, respectively, and they significantly differed among the initial diameter, volume, and mass subgroups (all p values < 0.001). The growth pattern of pure ground-glass nodules may conform to exponential model.

2.
Biomed Res Int ; 2019: 7659239, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485445

RESUMO

Background: The purpose of this study was to investigate the correlation of the extent of aortic arch calcification (AAC) detectable on chest X-rays with the severity of coronary artery disease (CAD) as evaluated by the SYNTAX score (SS) in patients with acute coronary syndrome (ACS). Methods: A total of 1,418 patients (344 women; 59 ± 10 years) who underwent coronary angiography for ACS and were treated with coronary revascularization were included in the present study; chest X-rays were performed on admission. The AAC extent was divided into four grades (0-3). SS was calculated based on each patient's coronary angiographic findings. The relationship between the AAC extent and SS was assessed. Results: The AAC extent was positively correlated with SS (ρ = 0.639, P < 0.001). In the multivariate analysis, compared with grade 0, odds ratios (ORs) of AAC grades 1, 2, and 3 in predicting SS >22 were 12.95 (95% CI, 7.85-21.36), 191.76 (95% CI, 103.17-356.43), and 527.81 (95% CI, 198.24-1405.28), respectively. Receiver operating characteristic curve analysis yielded a strong predictive ability of the AAC extent for SS >22 (area under curve = 0.840, P < 0.001). Absence of AAC had a sensitivity, specificity, positive prognostic value, negative prognostic value, and accuracy of 46.7%, 95.9%, 94.1%, 56.4%, and 67.3%, respectively, for SS ≤22. AAC grades ≥2 had a sensitivity of 66.3%, specificity of 89.2%, positive prognostic value of 81.5%, negative prognostic value of 78.6%, and accuracy of 79.6% for the correct identification of SS >22. Conclusions: The extent of AAC detectable on chest X-rays might provide valuable information in predicting CAD severity in ACS patients.

3.
Medicine (Baltimore) ; 98(35): e16985, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464947

RESUMO

RATIONALE: Angiostrongylus cantonensis-induced eosinophilic meningoencephalitis (AEM) in infants is a very rare but fatal disease. Utilization of genetic assay to detect the cerebral parasite plays an important role for the treatment of the infection. PATIENT CONCERNS: Two infants (<2 years) presented with cough, intermittent fever, mental fatigue, and poor diet. DIAGNOSIS: The patients were under clinical examination and laboratory test including cardiac ultrasound, chest X-ray, blood or cerebrospinal fluid (CSF) cell counting, serum enzyme-linked immunosorbent assay (ELISA), head magnetic resonance imaging (MRI) and next-generation sequencing (NGS) on DNA from CSF. Due to hypereosinophils in patients' peripheral blood and CSF, and abundant DNA sequences from A cantonensis in CSF, the patients were diagnosed with Angiostrongylus eosinophilic meningoencephalitis. INTERVENTIONS: The patients were treated with albendazole to deworm, and methylprednisolone to reduce inflammation. OUTCOME: The patients were completely recovered from AEM without relapse after 10-day treatment. LESSONS: ELISA and MRI are not sufficiently accurate for the diagnosis of AEM in infants. NGS can specify the infection by the cerebral parasite and offers a new effective approach for the early and precise diagnosis of AEM in infants.

4.
Cell Signal ; 63: 109378, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31369826

RESUMO

B lymphocytes, a key cluster of cells composing the immune system, can protect against abnormal biological factors. Heme oxygenase-1 (HO-1) plays important roles in cell proliferation and immune regulation, but its effects on the development and growth of B lymphocytes are still unknown. Herein, the count of B lymphocytes in HO-1 gene knockout (HO-1+/-) mice was significantly lower than that of the HO-1 gene wild-type (HO-1WT) mice. Meanwhile, the cell count of HO-1+/- mice did not recover after irradiation for one week, due to the G0/G1 phase arrest of Pro-B cells and the augmented apoptosis of Pre-B cells. Up-regulation of HO-1 by lentivirus attenuated the Pro-B cell cycle arrest and Pre-B cell apoptosis. To understand the molecular mechanism by which HO-1 knockout blocked B lymphocyte development, protein-to-protein interaction network and Western blot were used. The PI3K/AKT signaling pathway mediated the regulatory effects of HO-1 on B lymphocytes. In conclusion, HO-1 is a crucial transcriptional repressor for B cell development.

5.
Ecotoxicol Environ Saf ; 183: 109562, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31437726

RESUMO

Presence of cadmium (Cd) in food poses serious risks to human health. Understanding the effects of zinc (Zn) on Cd absorption by crops could help provide a theoretical basis for the treatment with Zn on contaminated soils. In this study, two wheat varieties, differing in grain-Cd accumulation ability (L979, a Cd low-accumulation variety, and H27, a high-accumulation variety) were selected to investigate the effect of Zn addition on Cd toxicity. Cd was applied to nutrient solutions at 0 and 10 µM, and added Zn were 0, 50 and 100 µM. Zn supplements alleviated decreases in biomass induced by Cd toxicity for both varieties, and both varieties had different reduced concentrations of Cd in their shoots. Application of 50 µM Zn to H27 resulted in a 17% decrease in Cd concentrations. When treated with 100 µM Zn, only L979 showed a reduction in Cd concentration. The higher proportion of Cd in the soluble fraction was found in L979. In addition, ion-selective scanning at the root-surface indicated that Zn supplements reduced net root Cd2+ flux by 55% for L979, and 69% for H27. These mitigating effects of Zn in both varieties involved mechanisms related to photosynthesis, root growth, and antioxidant production. Additionally, both Zn available in the medium and absorbed in plant tissue causes antagonistic effects on Cd absorption for wheat. It seemed that vacuolar compartmentation could contribute Cd detoxification especially for low accumulation variety.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31372954

RESUMO

The emergence of antibiotic resistance genes (ARGs) in microbes can be largely attributed to the abuse and misuse of antibiotics and biocides. Quaternary ammonium compounds (QACs) have been used worldwide as common disinfectants and detergents; however, their potential impact on the spread and diffusion of ARGs is still unknown. In this study, we detected the QAC resistance gene (qacEΔ1), the 1 integron gene (intI1), and 12 ARGs (sul1, sul2, cfr, cml, fexA, tetA, tetG, tetQ, tetX, ermB, blaTEM, and dfrA1) in 48 water samples from three watersheds by quantitative PCR (qPCR). We investigated the evolution of bacterial antibiotic resistance under QAC and antibiotic environmental pressures by long-term continuous culture. In addition, five QACs were selected to investigate the effect of QAC on the efficiency of conjugation transfer. The changes in bacterial cell membrane and production of reactive oxygen species (ROS) were detected by flow cytometry, revealing the mechanism by which QAC affects the spread of antibiotic resistance. Our results showed that the QAC resistance gene was ubiquitous in watersheds and it had significant correlation with intI1 and seven ARGs (r = 0.999, p < 0.01). QACs could increase the resistance of bacteria to multiple antibiotics. Furthermore, all five QACs promoted the conjugation transfer of the RP4 plasmid; the optimal concentration of QACs was about 10-1-10-2 mg/L and their transfer efficiencies were between 1.33 × 10-6 and 8.87 × 10-5. QACs enhanced membrane permeability of bacterial cells and stimulated bacteria to produce ROS, which potentially promoted the transfer of plasmids between bacteria. In conclusion, this study demonstrated that QACs may facilitate the evolution and gene transfer of antibiotic resistance gene among microbiome.

7.
Bioresour Technol ; 291: 121920, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31382094

RESUMO

An anoxic/oxic membrane bioreactor (AO-MBR), an anaerobic side-stream reactor (ASSR) coupled MBRs (A-MBRs), an A-MBR with carriers packed in ASSR (AP-MBR) and an AP-MBR with sludge ultrasonicated before ASSR (AUP-MBR) were operated for 261 d to investigate effects of ASSR, packing carriers and ultrasonication on sludge reduction and microbial population. Sludge reduction efficiencies of A-MBR, AP-MBR and AUP-MBR were 36.2%, 46.4% and 51.4%, respectively. Packing carriers and ultrasonication both enhanced hydrolysis by stimulating activities of α-glucosidase and protease, while uncoupling metabolism was enhanced greatly by packing carriers but slightly by ultrasonication. Linear discriminant analysis of effect size (LEfSe) results showed that packing carriers promoted the growth of hydrolytic and fermentative bacteria in bulk sludge, and enriched anaerobes and fermentative bacteria on the surface of carriers. Ultrasonication screened ultrasonication-resistant bacteria, and created an anaerobic environment beneficial to hydrolytic and fermentative bacteria.

8.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(6): 731-735, 2019 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-31270054

RESUMO

OBJECTIVE: To evaluate the long-term clinical outcomes of two-stage closed sinus lift for the maxillary sinus with residual bone height (RBH) of 1-3 mm in the posterior maxillary. METHODS: Seventy-eight patients with maxillary posterior tooth loss (1 mm≤RBH≤3 mm and alveolar ridge width ≥5 mm) were treated with two-stage closed sinus lift at the Dental Implantation Center of our hospital between March, 2012 and December, 2014. Coral hydroxyapatite powder and 148 implants were implanted. The superstructure was fixed within 6 months after the operation and the patients were followed up for 1-5 years for assessing the patients' satisfaction, postoperative response, stability and survival rates of the implant, soft tissue condition, bone height of maxillary sinus floor elevation and the marginal bone loss. RESULTS: Perforation of the maxillary sinus floor occurred in 3 (3.85%) of the cases. Twenty-three (30.67%) patients complained of mild pain, and 52 (69.33%) did not experience headache or fever or reported obvious pain or swelling after the operation. The overall response to the operation was favorable. The ISQ value was 58.39±1.39 immediately after the operation, and increased significantly to 81.88±1.22 at 6 months (P < 0.05). During the healing period and the follow-up, none of the implants fell off, and the implant survival rate was 100%. The peri-implant probing depth and modified sulcus bleeding index at 1 year after sinus lifting were similar to those at 5 years after the operation (P > 0.05), but the sinus floor elevation and marginal bone resorption at the two time points differed significantly (P < 0.05). CONCLUSIONS: Compared with lateral wall lifting, two-stage close lifting of the maxillary sinus floor is associated with less trauma and less discomfort, and effectively solves the problem of severe alveolar bone height deficiency in the maxillary posterior region to achieve favorable long-term clinical outcomes.


Assuntos
Reabsorção Óssea , Levantamento do Assoalho do Seio Maxilar , Implantação Dentária Endo-Óssea , Seguimentos , Humanos , Maxila , Seio Maxilar , Resultado do Tratamento
9.
Environ Sci Process Impacts ; 21(8): 1393-1402, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31322150

RESUMO

The hydroxyl radical (OH) is one of the most important oxidants controlling the oxidation capacity of the indoor atmosphere. One of the main OH sources indoors is the photolysis of nitrous acid (HONO). In this study, real-time measurements of HONO, nitrogen oxides (NOx) and ozone (O3) in an indoor environment in Guangzhou, China, were performed under two different conditions: (1) in the absence of any human activity and (2) in the presence of cooking. The maximum NOx and HONO levels drastically increased from 15 and 4 ppb in the absence of human activity to 135 and 40 ppb during the cooking event, respectively. The photon flux was determined for the sunlit room, which has a closed south-east oriented window. The photon flux was used to estimate the photolysis rate constants of NO2, J(NO2), and HONO, J(HONO), which span the range between 8 × 10-5 and 1.5 × 10-5 s-1 in the morning from 9:30 to 11:45, and 8.5 × 10-4 and 1.5 × 10-4 s-1 at noon, respectively. The OH concentrations calculated by photostationary state (PSS) approach, observed around noon, are very similar, i.e., 2.4 × 106 and 3.1 × 106 cm-3 in the absence of human activity and during cooking, respectively. These results suggest that under "high NOx" conditions (NOx higher than a few ppb) and with direct sunlight in the room, the NOx and HONO chemistry would be similar, independent of the geographic location of the indoor environment, which facilitates future modeling studies focused on indoor gas phase oxidation capacity.

10.
Acta Crystallogr C Struct Chem ; 75(Pt 7): 990-995, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271389

RESUMO

A new coordination polymer (CP), namely poly[(µ-4,4'-bipyridine)(µ3-3,4'-oxydibenzoato)cobalt(II)], [Co(C14H8O5)(C10H8N2)]n or [Co(3,4'-obb)(4,4'-bipy)]n (1), was prepared by the self-assembly of Co(NO3)2·6H2O with the rarely used 3,4'-oxydibenzoic acid (3,4'-obbH2) ligand and 4,4'-bipyridine (4,4'-bipy) under solvothermal conditions, and has been structurally characterized by elemental analysis, IR spectroscopy, single-crystal X-ray crystallography and powder X-ray diffraction (PXRD). Single-crystal X-ray diffraction reveals that each CoII ion is six-coordinated by four O atoms from three 3,4'-obb2- ligands, of which two function as monodentate ligands and the other as a bidentate ligand, and by two N atoms from bridging 4,4'-bipy ligands, thereby forming a distorted octahedral CoN2O4 coordination geometry. Adjacent crystallographically equivalent CoII ions are bridged by the O atoms of 3,4'-obb2- ligands, affording an eight-membered Co2O4C2 ring which is further extended into a two-dimensional [Co(3,4'-obb)]n sheet along the ab plane via 3,4'-obb2- functioning as a bidentate bridging ligand. The planes are interlinked into a three-dimensional [Co(3,4'-obb)(4,4'-bipy)]n network by 4,4'-bipy ligands acting as pillars along the c axis. Magnetic investigations on CP 1 disclose an antiferromagnetic coupling within the dimeric Co2 unit and a metamagnetic behaviour at low temperature resulting from intermolecular π-π interactions between the parallel 4,4'-bipy ligands.

11.
Ann Intern Med ; 171(1): 73, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31261397
12.
J Chem Phys ; 150(20): 204507, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31153173

RESUMO

Glassy materials are nonequilibrium and their energy states have crucial influences on properties. Recent studies have shown that oscillating deformations (vibrations) can cause either accelerated aging (lowering energy) or rejuvenation (elevating energy); however, the underlying atomic mechanisms remain elusive. Using metallic glasses (MGs) as model systems, we show that the vibration-induced accelerated aging is correlated with the strain field of the stringlike atomic motions stemming from the Johari-Goldstein (ß) relaxation, whereas the rejuvenation is associated with nonlinear response and the formation of nanoscale shear bands attributing to the activation of α relaxation. Both processes are affected by thermal fluctuations, which result in an optimal temperature for accelerated aging. These results suggest intrinsic correlations among relaxation dynamics, mechanical properties, and the vibration induced structural rearrangements in MGs.

14.
Chin J Nat Med ; 17(5): 387-393, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31171274

RESUMO

Replacement of the native promoter of theglobal regulator LaeA-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism (ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

15.
Top Curr Chem (Cham) ; 377(3): 18, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161309

RESUMO

Manganese(III) porphyrin complexes with various metal-containing/non-metal bridges reported during the past two decades, including their structural characteristics and magnetic properties, are summarized. As the porphyrin ligands usually adopt a planar chelate form, it is possible that the porphyrin-based complexes, being a coordination-acceptor building block, have two coordination labile sites in trans positions. In particular, the coordination labile sites in an octahedral field face the direction of the Jahn-Teller elongated axis occupying the dz2 orbital. As a result of this characteristic orbital arrangement, the activity and magnetic-electronic properties of the manganese complexes can be tuned by modulating the porphyrin ligand, which is equatorially located around the manganese ion and coupled with the dx2-y2 orbital. The high-spin Mn(III) porphyrin complexes (S = 2) display strong magnetic uniaxial anisotropy with the Jahn-Teller axis as the magnetic easy axis. So far, various manganese(III) porphyrin magnetism systems, including multinuclear clusters, one-dimensional chains, and two- or three-dimensional networks, have been designed and structurally and magnetically characterized. This review shows that the manganese(III) porphyrin complexes have potential as versatile sources for the design of unique magnetic materials as well as other molecular functional materials with various structures.


Assuntos
Imãs/química , Metaloporfirinas/química , Complexos de Coordenação/química , Cristalografia por Raios X , Cianetos/química , Dimerização , Magnetismo/métodos , Modelos Moleculares
16.
J Hazard Mater ; 377: 267-273, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31173975

RESUMO

The coexistence of arsenic (As) and fluoride (F) in drinking water is an urgent environmental issue that causes increasing public concerns. The need for effective simultaneous removal of As and F has motived great research efforts. Herein, a novel {201}TiO2-ZrO2 composite was synthesized and its application mechanism was explored. Batch adsorption experiments show that the As(III), As(V), and F adsorption followed the pseudo-second-order kinetics with the Langmuir adsorption capacity at 58.5, 21.6, and 13.1 mg/g, respectively. EXAFS and in situ ATR-FTIR results suggested that TiO2 surface sites were occupied by As(III) and As(V) in bidentate binuclear structures, and ZrO2 sites preferentially adsorbed As(III) and F in monodentate mononuclear configurations. This molecular structure obtained in the mono-adsorption system was integrated with the charge distribution multisite surface complexation model to accurately predict the As and F co-existing adsorption behaviors. The results in competitive adsorption, regeneration, and application evidenced that the {201}TiO2-ZrO2 composite is a promising adsorbent for simultaneous As and F removal.

17.
Acta Crystallogr C Struct Chem ; 75(Pt 6): 657-666, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31166917

RESUMO

Reaction of the flexible phenolic carboxylate ligand 2-(3,5-dicarboxylbenzyloxy)benzoic acid (H3L) with nickel salts in the presence of 1,2-bis(pyridin-4-yl)ethylene (bpe) leads to the generation of a mixture of the two complexes under solvolthermal conditions, namely poly[[aqua[µ-1,2-bis(pyridin-4-yl)ethylene-κ2N:N']{µ-5-[(2-carboxyphenoxy)methyl]benzene-1,3-dicarboxylato-κ3O1,O1':O3}nickel(II)] dimethylformamide hemisolvate monohydrate], {[Ni(C16H10O7)(C12H10N2)(H2O)]·0.5C3H7NO·H2O}n or {[Ni(HL)(bpe)(H2O)]·0.5DMF·H2O}n, 1, and poly[[diaquatris[µ-1,2-bis(pyridin-4-yl)ethylene-κ2N:N']bis{µ-5-[(2-carboxyphenoxy)methyl]benzene-1,3-dicarboxylato-κ2O1:O5}nickel(II)] dimethylformamide disolvate hexahydrate], {[Ni2(C16H10O7)2(C12H10N2)3(H2O)2]·2C3H7NO·6H2O}n or {[Ni2(HL)2(bpe)3(H2O)2]·2DMF·6H2O}n, 2. In complex 1, the NiII centres are connected by the carboxylate and bpe ligands to form two-dimensional (2D) 4-connected (4,4) layers, which are extended into a 2D+2D→3D (3D is three-dimensional) supramolecular framework. In complex 2, bpe ligands connect to NiII centres to form 2D layers with Ni6(bpe)6 metallmacrocycles. Interestingly, 2D+2D→3D inclined polycatenation was observed between these layers. The final 5-connected 3D self-penetrating structure was generated through further connection of Ni-carboxylate chains with these inclined motifs. Both complexes were fully characterized by single-crystal analysis, powder X-ray diffraction analysis, FT-IR spectra, elemental analyses, thermal analysis and UV-Vis spectra. Notably, an interesting metal/ligand-induced crystal-to-crystal transformation was observed between the two complexes.

18.
Bioresour Technol ; 289: 121643, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228743

RESUMO

Effects of microaeration pretreatment on sludge hydrolysis, biogas production and microbial community structure in anaerobic digestion (AD) were investigated by bench-scale tests and semi-continuous experiments. Bench tests showed that microaeration led to the release of dissolved organic matters, generation of volatile fatty acids and stimulation of enzyme activity. Correlation analysis showed that methane production was significantly correlated with the activity of α-glucosidase at 0.01 level, and with protease activity, released polysaccharides and VFAs at 0.05 level. Semi-continuous experiments showed that microaeration accelerated the utilization of organic matters, increased biogas production by 16.4%, enhanced methane content in biogas, and improved sludge dewaterability. Microbial community structure analysis showed that microaeration promoted enrichment of hydrolytic and fermentative bacteria in AD reactor rather than methanogenic bacteria, and aceticlastic methanogenesis was the main methanogenic pathway for methane production.

19.
Life Sci ; 232: 116583, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31226417

RESUMO

TP53 mutation is an indicator of poor prognostic in chronic lymphocytic leukemia (CLL). Worse still, CLL patients with TP53 mutation are associated with poor efficacy to current chemotherapeutic, such as Fludarabine. Here, we confirmed that high expression of HDAC1 in CLL patients with TP53 mutation, which is closely related to poor prognosis and drug-resistance. Subsequently, we demonstrated Entinostat (HDAC1 inhibitor) combination with Fludarabine significantly induced apoptosis in TP53 mutations CLL cells. Its mechanism was associated with up-regulation of the pro-apoptotic protein Bax and the down-regulation of HDAC1, HO-1 and BCL-2 proteins. More importantly, we also confirmed that upregulation of HDAC1 could resistant Entinostat-induced apoptosis in TP53 mutations CLL cells by activating the HDAC1/P38/HO-1 pathway. In vivo, we found that Entinostat combination with Fludarabine significantly induced tumor cells apoptosis and prolong survival time in xenograft mouse model. Finally, combining vitro and vivo experiments, we presented the first demonstration that Entinostat combination with Fludarabine had a synergistic effect on the induction of apoptosis in TP53 mutations CLL cells. In conclusion, we provide valuable pre-clinical experimental evidence for the treatment of CLL patients with poor prognosis, especially for TP53 mutations.

20.
J Am Coll Cardiol ; 73(25): 3362, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31248565
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