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1.
Medicine (Baltimore) ; 99(5): e18341, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000355

RESUMO

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) has contributed to an increasing number of deaths and readmissions over the past few decades. Despite the appearance of standard treatments, including diuretics, ß-receptor blockers and angiotensin-converting enzyme inhibitor (ACEI), there are still a large number of patients who have progressive deterioration of heart function and, inevitably, end-stage heart failure. In recent years, new medications for treating chronic heart failure have been clinically applied, but there is controversy surrounding drug selection and whether patients with HFrEF benefit from these medications. Therefore, we aimed to compare and rank different new pharmacological treatments in patients with HFrEF. METHODS: We performed a network meta-analysis to identify both direct and indirect evidence from relevant studies. We searched MEDLINE, EMBASE, and PsycINFO through the OVID database and CENTRAL through the Cochrane Library for clinical randomized controlled trials investigating new pharmacological treatments in patients with HFrEF published up to September 30, 2018. We included trials of ivabradine, levosimendan, omega-3, tolvaptan, recombinant human B-type natriuretic peptide (rhBNP), isosorbide dinitrate and hydralazine (ISDN/HYD) and angiotensin-neprilysin inhibition (LCZ696). We extracted the relevant information from these trials with a predefined data extraction sheet and assessed the risk of bias with the Cochrane risk of bias tool. Based on these items, more than half of the entries were judged as having an overall low to moderate risk of bias; the remaining studies had a high or unclear risk of bias. The outcomes investigated were left ventricle ejection fraction (LVEF %), heart rate (HR) and serum level of B-type natriuretic peptide (BNP). We performed a random-effects network meta-analysis within a Bayesian framework. RESULTS: We deemed 32 trials to be eligible that included 3810 patients and 32 treatments. Overall, 32 (94.1%) trials had a low to moderate risk of bias, while 2 (5.9%) trials had a high risk of bias. The quality of the included studies was rated as low in regard to allocation concealment and blinding and high in regard to other domains according to the Cochrane tools. As for increasing LVEF%, levosimendan was better than placebo (-3.77 (-4.96, -2.43)) and was the best intervention for improving ventricle contraction. As for controlling HR, n3-PUFA was better than placebo (4.01 (-0.44, 8.48)) and was the best choice for regulating HR. As for decreasing BNP, omega-3 was better than placebo (941.99 (-47.48, 1952.89) and was the best therapy for improving ventricle wall tension. CONCLUSIONS: Our study confirmed the effectiveness of the included new pharmacological treatments for optimizing the structural performance and improving the cardiac function in the management of patients with HFrEF and recommended several interventions for clinical practice.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Teorema de Bayes , Humanos , Volume Sistólico
2.
Biomark Med ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904263

RESUMO

Aim: Fatty acid synthase (FASN), a key enzyme for de novo synthesis of fatty acids, has been identified as an oncogene in some tumor types; however, the function of FASN in gastric cancer (GC) is poorly elucidated. Method: Integrative bioinformatics analyses were performed to unveil the role of FASN in tumor progression and cancer-associated immunology of GC. Result: FASN was overexpressed in the GC tissues and correlated with an inferior survival outcome, and largely contributed to the carcinogenesis of GC. Moreover, FASN expression was closely associated with the immune-infiltrating levels of CD8+ T, CD4+ T, neutrophils, macrophages and dendritic cells. Conclusion: FASN was closely associated with GC and may be involved in the tumorigenesis and cancer-immune interactions, and could be a promising prognostic and therapeutic biomarker in GC.

3.
Waste Manag Res ; : 734242X19896630, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31918637

RESUMO

In this study, the pyrolysis behaviour of nonmetal fraction of waste printed circuit boards (NMF-WPCBs) was studied based on five model-free methods and distributed activation energy model (DAEM). The possible decomposition mechanism was further probed using the Criado method. Thermogravimetric analysis indicated that the NMF-WPCBs pyrolysis process could be divided into three stages with temperatures of 37-330°C, 330-380°C and 380-1000°C. The mass loss at different heating rate was determined as 26.85-29.98%, 13.47-24.21% and 20.43-23.36% for these stages, respectively. The activation energy (Eα) from various model-free methods first increased with degree of conversion (α) increasing from 0.05 to 0.275, and then decreased beyond this range. The coefficient (R) from the Flynn-Wall-Ozawa (FWO) method was higher, and the resulting Eα fell into the range of 214.947-565.660 kJ mol-1. For the DAEM method, the average Eα value was determined as 337.044 kJ mol-1, comparable with 329.664 kJ mol-1 from the FWO method. The thermal decomposition kinetics of NMF-WPCBs could be better described by the second-order reaction.

4.
Waste Manag Res ; : 734242X19897814, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957598

RESUMO

In this work, the pyrolysis behavior of plastic waste-TV plastic shell-was investigated, based on thermogravimetric analysis and using a combination of model-fitting and model-free methods. The possible reaction mechanism and kinetic compensation effects were also examined. Thermogravimetric analysis indicated that the decomposition of plastic waste in a helium atmosphere can be divided into three stages: the minor loss stage (20-300°C), the major loss stage (300-500°C) and the stable loss stage (500-1000°C). The corresponding weight loss at three different heating rates of 15, 25 and 35 K/min were determined to be 2.80-3.02%, 94.45-95.11% and 0.04-0.16%, respectively. The activation energy (Ea) and correlation coefficient (R2) profiles revealed that the kinetic parameters calculated using the Friedman and Kissinger-Akahira-Sunose method displayed a similar trend. The values from the Flynn-Wall-Ozawa and Starink methods were comparable, although the former gave higher R2 values. The Eα values gradually decreased from 269.75 kJ/mol to 184.18 kJ/mol as the degree of conversion (α) increased from 0.1 to 0.8. Beyond this range, the Eα slightly increased to 211.31 kJ/mol. The model-fitting method of Coats-Redfern was used to predict the possible reaction mechanism, for which the first-order model resulted in higher R2 values than and comparable Eα values to those obtained from the Flynn-Wall-Ozawa method. The pre-exponential factors (lnA) were calculated based on the F1 reaction model and the Flynn-Wall-Ozawa method, and fell in the range 59.34-48.05. The study of the kinetic compensation effect confirmed that a compensation effect existed between Ea and lnA during the plastic waste pyrolysis.

5.
Waste Manag Res ; 38(1): 100-106, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31603400

RESUMO

Thermal treatment offers an alternative method for the separation of aluminum foil and cathode materials during spent lithium-ion batteries recycling. In this work, the combustion kinetic of cathode was studied based on six model-free (isoconversional) methods, namely Flynn-Wall-Ozawa (FWO), Friedman, Kissinger-Akahira-Sunose, Starink, Tang, and Boswell methods. The possible decomposition mechanism was also probed using a master-plots method (Criado method). Thermogravimetric analysis showed that the whole thermal process could be divided into three stages with temperatures of 37-578°C, 578-849°C, and 849-1000°C. The activation energy (Eα) derived from these model-free methods displayed the same trend, gradually increasing with a conversion range of 0.002-0.013, and significantly elevating beyond this range. The coefficients from the FWO method were larger, and the resulted Eα fell into the range of 10.992-40.298 kJ/mol with an average value of 20.228 kJ/mol. Comparing the theoretical master plots with an experimental curve, the thermal decomposition of cathode could be better described by the geometric contraction models.


Assuntos
Fontes de Energia Elétrica , Lítio , Eletrodos , Cinética , Termogravimetria
6.
Glia ; 68(2): 263-279, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31490574

RESUMO

Myelination delay and remyelination failure following insults to the central nervous system (CNS) impede axonal conduction and lead to motor, sensory and cognitive impairments. Both myelination and remyelination are often inhibited or delayed due to the failure of oligodendrocyte progenitor cells (OPCs) to mature into myelinating oligodendrocytes (OLs). Digestion products of the glycosaminoglycan hyaluronan (HA) have been implicated in blocking OPC maturation, but how these digestion products are generated is unclear. We tested the possibility that hyaluronidase activity is directly linked to the inhibition of OPC maturation by developing a novel modified flavonoid that functions as a hyaluronidase inhibitor. This compound, called S3, blocks some but not all hyaluronidases and only inhibits matrix metalloproteinase activity at high concentrations. We find that S3 reverses HA-mediated inhibition of OPC maturation in vitro, an effect that can be overcome by excess recombinant hyaluronidase. Furthermore, we find that hyaluronidase inhibition by S3 accelerates OPC maturation in an in vitro model of perinatal white matter injury. Finally, blocking hyaluronidase activity with S3 promotes functional remyelination in mice with lysolecithin-induced demyelinating corpus callosum lesions. All together, these findings support the notion that hyaluronidase activity originating from OPCs in CNS lesions is sufficient to prevent OPC maturation, which delays myelination or blocks remyelination. These data also indicate that modified flavonoids can act as selective inhibitors of hyaluronidase activity and can promote OPC maturation, making them excellent candidates to accelerate myelination or promote remyelination following perinatal and adult CNS insults.

7.
Chemistry ; 25(67): 15217, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31793089

RESUMO

Invited for the cover of this issue is the group of Min Zhang and Weiping Su at the Fujian Institute of Research on the Structure of Matter. Read the full text of the article at 10.1002/chem.201903551.

8.
J Orthop Surg Res ; 14(1): 446, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847866

RESUMO

BACKGROUND: Poly(vinyl alcohol) (PVA) hydrogels have been widely used in synthetic cartilage materials. However, limitations of PVA hydrogels such as poor biomechanics and limited cell ingrowth remain challenges in this field. METHODS: This work aimed to design novel nano-hydroxyapatite (nano-HA)/poly(vinyl alcohol) (PVA) hydrogels coated with a poly(lactic-co-glycolic acid) (PLGA)/nano-HA/PVA scaffold to counter the limitations of PVA hydrogels. The core, comprising nano-HA/PVA hydrogel, had the primary role of bearing the mechanical load. The peripheral structure, composed of PLGA/nano-HA/PVA, was designed to favor interaction with surrounding cartilage. RESULTS: The double-layer HA/PVA hydrogel coated with PLGA/HA/PVA scaffold was successfully prepared using a two-step molding method, and the mechanical properties and biocompatibility were characterized. The mechanical properties of the novel PLGA/HA/PVA scaffold modified HA/PVA hydrogel were similar to those of native cartilage and showed greater sensitivity to compressive stress than to tensile stress. Rabbit chondrocytes were seeded in the composites to assess the biocompatibility and practicability in vitro. The results showed that the peripheral component comprising 30 wt% PLGA/5 wt% HA/15 wt% PVA was most conducive to rabbit chondrocyte adhesion and proliferation. CONCLUSIONS: The study indicated that the double-layer HA/PVA hydrogel coated with PLGA/HA/PVA scaffold has the potential for cartilage repair.

9.
Waste Manag Res ; : 734242X19877682, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599207

RESUMO

Thermal treatment offers advantages of significant volume reduction and energy recovery for the polyurethane foam from waste refrigerators. In this work, the pyrolysis kinetics of polyurethane foam was investigated using the model-fitting, model-free and distributed activation energy model methods. The thermogravimetric analysis indicated that the polyurethane foam decomposition could be divided into three stages with temperatures of 38°C-400°C, 400°C-550°C and 550°C-1000°C. Peak temperatures for the major decomposition stage (<400°C) were determined as 324°C, 342°C and 344°C for heating rates of 5, 15 and 25 K min-1, respectively. The activation energy (Eα) from the Friedman, Flynn-Wall-Ozawa and Tang methods increased with degree of conversion (α) in the range of 0.05 to 0.5. The coefficients from the Flynn-Wall-Ozawa method were larger and the resulted Eα values fell into the range of 163.980-328.190 kJ mol-1 with an average of 206.099 kJ mol-1. For the Coats-Redfern method, the diffusion models offered higher coefficients, but the E values were smaller than that from the Flynn-Wall-Ozawa method. The Eα values derived from the distributed activation energy model method were determined as 163.536-334.231 kJ mol-1, with an average of 206.799 kJ mol-1. The peak of activation energy distribution curve was located at 205.929 kJ mol-1, consistent with the thermogravimetric results. The Flynn-Wall-Ozawa and distributed activation energy model methods were more reliable for describing the polyurethane foam pyrolysis process.

10.
Chemistry ; 25(67): 15233-15238, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31495987

RESUMO

Herein, an oxidization reaction of enones with a CuII complex that leads to a new type of regioselective [3+2] cycloaddition is reported. Highly functionalized cyclopentenes and spirocyclic compounds are obtained in moderate-to-good yields. This cycloaddition reaction occurred through the formation of γ-enone radicals, providing a rarely explored reactivity pattern for enones.

11.
Environ Sci Pollut Res Int ; 26(31): 31581-31591, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502055

RESUMO

Shellfish cultivation is an expanding economic activity worldwide. However, the rapid development of crab farming and processing result in a large number of crab shells (CS). Utilizing CS could not only benefit the environment and economy but also promote the sustainable development of aquaculture. In this work, it reviews and analyzes recent attempts in CS recycling, including extracting chitin and its derivatives, for use as adsorbent and flocculant and for preparing polymer composites and catalysts, as well as medical applications. The challenges in these utilizations are discussed, and future research directions are proposed as well. Extracting chitin and its derivates, for use as adsorbent and flocculant, are recent major recycling approaches. Preparing polymer composites and carbon materials has gained more and more attentions. Biotechnology is an alternative method for extracting chitin and its derivates from CS, and high-efficiency desalted and deproteinized bacteria need to be screened. Immobilizing the CS-based adsorbents is the key of treating wastewater in continuous systems. Using CS as a biofiller to prepare polymer composites is promising, and surface modification to improve the interfacial compatibility between CS-based fillers and matrix needs to be further studied.

12.
Front Oncol ; 9: 683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403034

RESUMO

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare type of lymphoma with a high incidence in elderly patients, poor drug response, and unfavorable prognosis. Despite advances in genomic profiling and precision medicine in DLBCL, EBV+ DLBCL remain poorly characterized and understood. We include 236 DLBCL patients for EBV-encoded mRNA (EBER) in situ hybridization detection and analyzed 9 EBV+ and 6 EBV negative cases by next-generation sequencing (NGS). We then performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to analyze chromosome rearrangements and gene expressions in 22 EBV+ and 30 EBV negative cases. The EBER results showed a 9.3% (22/236) positive rate. The NGS results revealed recurrent alterations in MYC and RHOA, components of apoptosis and NF-κB pathways. The most frequently mutated genes in EBV+ DLBCL were MYC (3/9; 33.3%), RHOA (3/9; 33.3%), PIM1 (2/9; 22.2%), MEF2B (2/9; 22.2%), MYD88 (2/9; 22.2%), and CD79B (2/9; 22.2%) compared with KMT2D (4/6; 66.7%), CREBBP (3/6; 50.0%), PIM1 (2/6; 33.3%), TNFAIP3 (2/6; 33.3%), and BCL2 (2/6; 33.3%) in EBV-negative DLBCL. MYC and KMT2D alterations stood out the most differently mutated genes between the two groups. FISH detection displayed a lower rearrangement rate in EBV+ cohort. Furthermore, KMT2D expression was highly expressed and associated with poor survival in both cohorts. MYC was only overexpressed and related to an inferior prognosis in the EBV+ DLBCL cohort. In summary, we depicted a distinct mutation profile for EBV+ and EBV-negative DLBCL and validated the differential expression of KMT2D and MYC with potential prognostic influence, thereby providing new perspectives into the pathogenesis and precision medicine of DLBCL.

13.
Nat Commun ; 10(1): 3681, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417081

RESUMO

Metal-catalyzed ß-C-H functionalization of saturated carbonyls via dehydrogenative desaturation proved to be a powerful tool for simplifying synthesis of valuable ß-substituted carbonyls. Here, we report a copper-catalyzed dehydrogenative γ-C(sp3)-H amination of saturated ketones that initiates the three-component coupling of saturated ketones, amines and N-substituted maleimides to construct polysubstituted anilines. The protocol presented herein enables both linear and α-branched butanones to couple a wide spectrum of amines and various N-substituted maleimides to produce diverse tetra- or penta-substituted anilines in fair-to-excellent yields with good functional group tolerance. The mechanism studies support that this ketone dehydrogenative γ-C(sp3)-H amination was triggered by the ketone α,ß-dehydrogenation desaturation that activates the adjacent γ-C(sp3)-H bond towards functionalization. This α,ß-dehydrogenation desaturation-triggered cascade sequence opens up a new avenue to the remote C(sp3)-H functionalization of saturated ketones and has the potential to enable the rapid syntheses of complex compounds from simple starting materials.

14.
J Knee Surg ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434148

RESUMO

Diffuse-type pigmented villonodular synovitis is a rare benign disease that causes disorders of the knee, including erosion of subchondral bone and cyst formation, with eventual osteoarthritis. The purpose of this study was to evaluate the short-term outcomes of synovectomy and total knee replacement in patients with the diffuse type of pigmented villonodular synovitis. From November 2011 to May 2015, we performed synovectomy and total knee replacement in 28 patients with diffuse pigmented villonodular synovitis diagnosed on the basis of histopathology of biopsy specimens. Clinical data were collected perioperatively and during follow-up for evaluation of surgical efficacy. No intraoperative complications were encountered. Mean operative duration was 73.4 minutes (range: 47-115 minutes); mean estimated blood loss was 223.9 mL (range: 50-600 mL). The mean duration of follow-up was 58.7 months (range: 36-84 months). Mean range of motion improved from 86.1 ± 11.3 degrees (range: 60-100 degrees) to 107 ± 11.4 degrees (range: 90-130 degrees). Average Knee Society clinical scores improved from 38.9 ± 9.5 (range: 17-54) to 84.4 ± 6.1 (range: 75-98); functional scores improved from 48.9 ± 13.1 (range: 25-80) to 84.6 ± 6.1 (range: 75-95; p < 0.05 for both). Postoperative radiographs showed no signs of prosthesis loosening, periprosthetic fractures, or dislocation. The short-term efficacy of synovectomy and total knee replacement in treating patients with diffuse pigmented villonodular synovitis was satisfactory.

15.
Chem Commun (Camb) ; 55(64): 9547-9550, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31334711

RESUMO

Rh-catalyzed reactions of N-alkyl anilines with internal alkynes at room temperature have been developed using an in situ generated N-nitroso group as a transient oxidizing directing group. Due to mild reaction conditions, this method enabled synthesis of a broad range of N-alkyl indoles, including even two indole-based medicinal compounds. Our work disclosed the feasibility of the transient oxidizing directing group strategy in C-H functionalization reactions, which possesses the potential to enhance overall step-economy and impart new reactivity patterns to substrates.

16.
Med Sci Monit ; 25: 5028-5035, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31280283

RESUMO

BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway. MATERIAL AND METHODS Compound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression. RESULTS The constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression. CONCLUSIONS HSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.


Assuntos
Constipação Intestinal/tratamento farmacológico , Fibras na Dieta/uso terapêutico , Intestinos/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Água/metabolismo , Animais , Aquaporina 3/genética , Aquaporina 3/metabolismo , Constipação Intestinal/sangue , Constipação Intestinal/genética , Constipação Intestinal/fisiopatologia , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fibras na Dieta/farmacologia , Fezes , Microbioma Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Dureza , Umidade , Polissacarídeos/química , Polissacarídeos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Transcrição Genética/efeitos dos fármacos , Resultado do Tratamento , Peptídeo Intestinal Vasoativo/sangue , Peptídeo Intestinal Vasoativo/genética
17.
Sci Total Environ ; 675: 651-657, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31039499

RESUMO

In this work, the combustion and pyrolysis characteristics of a waste TV plastic shell sample were investigated using a powerful Thermogravimetric-Fourier Infrared Spectrum-Mass Spectrum (TG-FTIR-MS) technique. The decomposition mechanisms of plastic waste and fate of bromines in both thermal processes were probed as well. The TG analysis revealed that the combustion rate was larger than that of pyrolysis at temperature of 456 °C below, whereas it decreased at temperature of 456-605 °C. As a result, the total weight loss was equivalent at temperature of 605 °C for both processes. The FTIR analysis indicated the plastic combusted vigorously at 300-500 °C and 800-900 °C. As a comparison, it decomposed drastically at 300-400 °C and 500-900° in pyrolysis. The MS analysis showed that the release of brominated products HBr, CH3Br, C2H5Br, C3H5Br, C3H7Br and C3H5BrO increased with an increase of temperature and reached maximum at 400-600 °C in both thermal processes. The release intensities of larger molecules C6H5Br, C6H5BrO and C6H4Br2 were in the descending order of C6H5Br > C6H4Br2 > C6H5BrO. It was not significant in the evolved products and decomposition pathway for both thermal processes. The entire decomposition of TV plastic shell sample could be divided into three stages, taking account of the evolved products. The backbone in acrylonitrile butadiene styrene resin and tetrabromobisphenol A first broke at 350 °C below, resulting in the form of 2-bromophenol, styrene, acrylonitrile and polybutadiene. Subsequently, the resulted 2-bromophenol debrominated forming HBr, which further reacted with hydrocarbons resulting in various brominated derivates. In addition, many small molecules, including CO2, CO and CH4 were generated in this stage. Further increasing temperature to 550 °C above, larger brominated derivates decomposed and smaller molecules predominated.

18.
Matrix Biol ; 78-79: 272-283, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29408010

RESUMO

Adult neurogenesis in mammals is a tightly regulated process where neural stem cells (NSCs), especially in the subgranular zone (SGZ) of the hippocampal dentate gyrus, proliferate and differentiate into new neurons that form new circuits or integrate into old circuits involved in episodic memory, pattern discrimination, and emotional responses. Recent evidence suggests that changes in the hyaluronan (HA)-based extracellular matrix of the SGZ may regulate neurogenesis by controlling NSC proliferation and early steps in neuronal differentiation. These studies raise the intriguing possibility that perturbations in this matrix, including HA accumulation with aging, could impact adult neurogenesis and cognitive functions, and that alterations to this matrix could be beneficial following insults to the central nervous system that impact hippocampal functions.


Assuntos
Envelhecimento/metabolismo , Ácido Hialurônico/metabolismo , Células-Tronco Neurais/citologia , Neurogênese , Envelhecimento/fisiologia , Animais , Diferenciação Celular , Proliferação de Células , Cognição , Matriz Extracelular/metabolismo , Humanos , Mamíferos , Células-Tronco Neurais/metabolismo , Nicho de Células-Tronco
19.
Nat Commun ; 9(1): 5002, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30479335

RESUMO

Enamine and imine represent two of the most common reaction intermediates in syntheses, and the imine intermediates containing α-hydrogen often exhibit the similar reactivity to enamines due to their rapid tautomerization to enamine tautomers. Herein, we report that the minor structural difference between the enamine and the enamine tautomer derived from imine tautomerization results in the different chemo- and regioselectivity in the reaction of cyclohexanones, amines and TEMPO: the reaction of primary amines furnishes the formal oxygen 1,2-migration product, α-amino-enones, while the reaction of secondary amines under similar conditions generates exclusively arylamines via consecutive dehydrogenation on the cyclohexyl rings. The 18O-labeling experiment for α-amino-enone formation revealed that TEMPO served as oxygen transfer reagent. Experimental and computational studies of reaction mechanisms revealed that the difference in chemo- and regioselectivity could be ascribed to the flexible imine-enamine tautomerization of the imine intermediate containing an α-hydrogen.

20.
Neoplasia ; 20(10): 1059-1069, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30227305

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma. The treatment of PCNSL is comprehensive, combining surgery, radiotherapy, and chemotherapy. However, the outcome is poor because of its high invasiveness and rate of recurrence. We analyzed 22 cases of PCNSL using next-generation sequencing (NGS) to detect 64 candidate genes. We used immunohistochemical methods to analyze gene expression in 57 PCNSL samples. NGS showed that recurrent mutations in KMT2D and CD79B, components of the NF-κB pathway, accounted for 65% of total mutations in PCNSL samples. The most frequent mutated gene was PIM1 (77.27%, 17/22), followed by MYD88 (63.64%, 14/22), CD79B (69.09%, 13/22), and KMT2D (50.00%, 11/22). Mutations of the CD79B gene were associated with an inferior progression-free survival (PFS), and GNA13 gene mutations were associated with a shorter PFS and overall survival (OS) in PCNSL patients (P < .05). PIM1 and MYD88 were highly expressed in PCNSL patients and were related to their OS time. MYD88 overexpression might be an independent and poor prognostic predictor of OS time. In summary, we identified highly recurrent genetic lesions in CD79B and KMT2D, components of the NF-κB pathway, in PCNSL and validated the expression of PIM1 and MYD88 related to poor survival, thereby providing novel insights into the pathogenesis and precision medicine of PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central/genética , Regulação Neoplásica da Expressão Gênica , Linfoma/genética , Mutação , Adolescente , Adulto , Idoso , Antígenos CD79/genética , Neoplasias do Sistema Nervoso Central/mortalidade , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Proteínas de Neoplasias/genética , Prognóstico , Proteínas Proto-Oncogênicas c-pim-1/genética , Proteínas Proto-Oncogênicas c-pim-1/metabolismo
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