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1.
Artigo em Inglês | MEDLINE | ID: mdl-31688246

RESUMO

PURPOSE: The purpose of this study was to evaluate the features of sclerosing angiomatoid nodular transformation (SANT) in spleen on the imaging of computed tomography (CT) and magnetic resonance (MR). MATERIALS AND METHODS: From July 2006 to April 2017, 12 patients with SANT confirmed by pathology were evaluated in a retrospective study. Eight patients were with CT imaging only, 2 patients were with MR imaging only, and 2 patients were with both CT and MR. Three professional senior radiologists analyzed the imaging features on CT and MR. The main characteristic analysis included size, margin, density, signal intensity, and enhancement pattern. The significant enhancement was defined as the degree of enhancement of lesion that is higher than the surrounding spleen parenchyma, and the mild enhancement was defined as the degree of enhancement of lesion that is lower than the surrounding spleen parenchyma. RESULTS: All the 12 patients (5 men, 7 women; mean age, 45.8 years; age range, 21-62 years) presented as single lesion without special clinical symptoms. The range of lesions on diameter was from 25 to 80 mm. On CT images, 9 (90%) of 10 presented as hypodense in comparison with the parenchyma of spleen, 1 (10%) of 10 presented as isodense, and calcification was observed in 4 (40%) of 10 cases. On MR images, 4 (100%) of 4 manifested heterogeneous hypointensity on in-phase sequence and 3 (75%) of 4 performed as isointensity on out-of-phase sequence of T1-weighted. On the sequences of T2-weighted and diffusion-weighted image, 4 (100%) of 4 showed hypointensity. On CT and MR enhancement images, the number of significant enhancement and mild enhancement was 2 and 10, respectively. Seven (58%) of 12 showed progressive enhancement with the pattern of "spoke-wheel." CONCLUSIONS: Imaging features on CT and MR have a high diagnostic value for SANT, especially when CT combined with MR examination.

2.
Theranostics ; 9(25): 7792-7806, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695801

RESUMO

Therapeutic antibodies are one most significant advances in immunotherapy, the development of antibodies against disease-associated MHC-peptide complexes led to the introduction of TCR-like antibodies. TCR-like antibodies combine the recognition of intracellular proteins with the therapeutic potency and versatility of monoclonal antibodies (mAb), offering an unparalleled opportunity to expand the repertoire of therapeutic antibodies available to treat diseases like cancer. This review details the current state of TCR-like antibodies and describes their production, mechanisms as well as their applications. In addition, it presents an insight on the challenges that they must overcome in order to become commercially and clinically validated.

3.
Sci Rep ; 9(1): 15883, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685898

RESUMO

The variational principle is used to construct a multi-symplectic structure of the generalized KdV-type equation. Accordingly, the local energy conservation law, the local momentum conservation law, and the Cartan form of the generalized KdV-type equation are given. An explicit multi-symplectic scheme for the generalized KdV equation based on the Fourier pseudo-spectral method and the symplectic Euler scheme is constructed. Through a numerical examination, the explicit multi-symplectic Fourier pseudo-spectral scheme for the generalized KdV equation not only preserve the discrete global energy conservation law and the global momentum conservation law with high accuracy, but show long-time numerical stability as well.

4.
J Surg Oncol ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705561

RESUMO

BACKGROUND: We previously reported a prospective study showing axillary lymph node dissection (ALND) is associated with increased breast skin thickening during and 6 weeks post-radiation therapy (RT), and now report ALND's long-term impact at 1 year. METHODS: Among 66 women who received whole breast RT after lumpectomy, objective ultrasound measurements of epidermal thickness over four quadrants of the treated breast were measured at five time points: before RT, week 6 of RT, and 6 weeks, 6 months, and 1 year post-RT. Skin thickness ratio (STRA) was generated by normalizing for corresponding measurements of the contralateral breast. RESULTS: A total of 2,436 ultrasound images were obtained. Among 63 women with evaluable data at 1 year, mean STRA significantly increased at 6 months (absolute mean increase of 65%, SD 0.054), and remained elevated at 1 year post-RT (absolute mean increase of 44%, SD 0.048). In multivariable analysis, ALND compared to sentinel lymph node biopsy, longer interval between surgery and RT, increased baseline STRA, and Caucasian race predicted for more severe changes in STRA at 1 year compared to baseline (all P < .05). CONCLUSIONS: In the setting of whole breast RT, our findings suggest that ALND has long-term repercussions on breast skin thickening.

5.
J Biol Chem ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719145

RESUMO

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo. We found that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found that these effects were not mediated by tubacin's inhibitory effect on HDAC6 activity, but rather were due to its ability to stabilize eNOS mRNA transcripts. Consistent with these findings, tubacin also inhibited proinflammatory cytokine-induced degradation of eNOS transcripts and impairment of endothelium-dependent relaxation in the mouse aorta. Furthermore, we found that tubacin-induced up-regulation in eNOS expression in vivo is associated with improved endothelial function in diabetic db/db mice and with a marked attenuation of ischemic brain injury in a murine stroke model. Our findings indicate that tubacin exhibits potent eNOS-inducing effects and suggest that this compound might be useful for the prevention or management of endothelial dysfunction-associated cardiovascular diseases.

6.
Oncol Rep ; 42(6): 2655-2669, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31661141

RESUMO

Persistent infection with high­risk human papillomavirus is known to cause cervical cancer. The binding of the costimulatory factors, Tim­3 and galectin­9, can cause immune tolerance and lead to immune escape during carcinogenesis. Epigenetic regulation is essential for Tim­3/galectin­9 expression, which affects the outcome of local cervical cancer infection. Hence, exploring the epigenetic regulatory mechanisms of costimulatory signaling by Tim­3/galectin­9 is of great interest for investigating the mechanisms through which these proteins are regulated in cervical cancer tumorigenesis. In this study, we report that E2F­1 and FOXM1 mediated by HPV18 E6 and E7 can enhance the transcriptional activity of Enhancer of zeste homolog 2 (EZH2) by binding to its promoter region, resulting in the induced expression of the EZH2­specific target protein, H3K27me3, which consequently reduces the expression of the downstream target gene, DNA (cytosine­5)­methyltransferase 3A (DNMT3A). EZH2 and H3K27me3 directly interact with the DNMT3A promoter region to negatively regulate its expression in HeLa cells. Moreover, the downregulated DNMT3A and the decreased methylation levels in HAVCR2/LGALS9 promoter regions in HeLa cells promoted the expression of Tim­3/galectin­9. Furthermore, the high expression of Tim­3/galectin­9 was associated with HPV positivity among patients with cervical cancer. Moreover, HAVCR2/LGALS9 promoter regions were hypermethylated in normal cervical tissues, and this hypermethylated status inhibited gene expression. On the whole, these findings suggest that EZH2, H3K27me3 and DNMT3A mediate the epigenetic regulation of the negative stimulatory molecules, Tim­3 and galectin­9 in cervical cancer which is associated with HPV18 infection.

7.
Phys Med Biol ; 64(21): 215016, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31622962

RESUMO

Attenuation correction (AC) of PET/MRI faces challenges including inter-scan motion, image artifacts such as truncation and distortion, and erroneous transformation of structural voxel-intensities to PET mu-map values. We propose a deep-learning-based method to derive synthetic CT (sCT) images from non-attenuation corrected PET (NAC PET) images for AC on whole-body PET/MRI imaging. A 3D cycle-consistent generative adversarial networks (CycleGAN) framework was employed to synthesize CT images from NAC PET. The method learns a transformation that minimizes the difference between sCT, generated from NAC PET, and true CT. It also learns an inverse transformation such that cycle NAC PET image generated from the sCT is close to true NAC PET image. A self-attention strategy was also utilized to identify the most informative component and mitigate the disturbance of noise. We conducted a retrospective study on a total of 119 sets of whole-body PET/CT, with 80 sets for training and 39 sets for testing and evaluation. The whole-body sCT images generated with proposed method demonstrate great resemblance to true CT images, and show good contrast on soft tissue, lung and bony tissues. The mean absolute error (MAE) of sCT over true CT is less than 110 HU. Using sCT for whole-body PET AC, the mean error of PET quantification is less than 1% and normalized mean square error (NMSE) is less than 1.4%. Average normalized cross correlation on whole body is close to one, and PSNR is larger than 42 dB. We proposed a deep learning-based approach to generate sCT from whole-body NAC PET for PET AC. sCT generated with proposed method shows great similarity to true CT images both qualitatively and quantitatively, and demonstrates great potential for whole-body PET AC in the absence of structural information.

8.
Medicine (Baltimore) ; 98(41): e17487, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593112

RESUMO

To analyze the association between glutathione S-transferases polymorphisms and the risk of cervical lesions.Case-control studies focusing on the association between glutathione S-transferase polymorphisms and the risk of cervical lesions were collected from the PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang databases from inception to August 2018. Pooled odds ratios and 95% confidence intervals were employed to evaluate the strength of the association. Subgroup analysis and sensitivity analysis were used to test the potential discrepancy and robustness, respectively.A total of 30 studies comprising 3961 patients and 4726 healthy controls satisfied the inclusion criteria. Of these, 6 studies contained information about GSTP1, 27 studies contained information about GSTM1, and 22 studies contained information about GSTT1. Our results supported that there was no statistical association between GSTP1 polymorphism and the risk of cervical lesions (odds ratio [OR] = 1.08, P = .40). The GSTM1 null variant showed increased susceptibility to cervical lesions (OR = 1.45, P < .001). Subgroup analysis revealed that the GSTM1 null variant caused cervical lesions among HPV infection cases (OR = 1.69, P = .02) and among the Chinese and Indian populations (OR = 2.24 and OR = 1.87, respectively, P < .001). The GSTT1 null variant increased the risk of cervical lesions in smokers (OR = 1.52, P = .03). The GSTT1 null genotype was also related to high-grade intraepithelial neoplasia (HSIL) and cervical cancer risk (OR = 1.30 and OR = 1.78, respectively, P < .05).The GSTM1 null variant caused cervical lesions, especially among HPV infection cases and among the Chinese and Indian populations. The GSTT1 null variant increased the risk of cervical lesions in smokers and was also related to HISL and cervical cancer risk.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias do Colo do Útero/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/virologia , China , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Humanos , Índia , Pessoa de Meia-Idade , Razão de Chances , Infecções por Papillomavirus/genética , Fatores de Risco , Neoplasias do Colo do Útero/virologia
9.
Radiother Oncol ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31630868

RESUMO

BACKGROUND AND PURPOSE: Manual contouring is labor intensive, and subject to variations in operator knowledge, experience and technique. This work aims to develop an automated computed tomography (CT) multi-organ segmentation method for prostate cancer treatment planning. METHODS AND MATERIALS: The proposed method exploits the superior soft-tissue information provided by synthetic MRI (sMRI) to aid the multi-organ segmentation on pelvic CT images. A cycle generative adversarial network (CycleGAN) was used to estimate sMRIs from CT images. A deep attention U-Net (DAUnet) was trained on sMRI and corresponding multi-organ contours for auto-segmentation. The deep attention strategy was introduced to identify the most relevant features to differentiate different organs. Deep supervision was incorporated into the DAUnet to enhance the features' discriminative ability. Segmented contours of a patient were obtained by feeding CT image into the trained CycleGAN to generate sMRI, which was then fed to the trained DAUnet to generate organ contours. We trained and evaluated our model with 140 datasets from prostate patients. RESULTS: The Dice similarity coefficient and mean surface distance between our segmented and bladder, prostate, and rectum manual contours were 0.95 ±â€¯0.03, 0.52 ±â€¯0.22 mm; 0.87 ±â€¯0.04, 0.93 ±â€¯0.51 mm; and 0.89 ±â€¯0.04, 0.92 ±â€¯1.03 mm, respectively. CONCLUSION: We proposed a sMRI-aided multi-organ automatic segmentation method on pelvic CT images. By integrating deep attention and deep supervision strategy, the proposed network provides accurate and consistent prostate, bladder and rectum segmentation, and has the potential to facilitate routine prostate-cancer radiotherapy treatment planning.

10.
J Vis Exp ; (151)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31609323

RESUMO

Increasing evidence shows that the microbiota-gut-brain axis plays an important role in the pathogenesis of brain diseases. Several studies also demonstrate that traumatic brain injuries cause changes to the gut microbiota. However, mechanisms underlying the bidirectional regulation of the brain-gut axis remain unknown. Currently, few models exist for studying the changes in gut microbiota after traumatic brain injury. Therefore, the presented study combines protocols for inducing traumatic brain injury using a lateral fluid percussion device and analysis of caecum samples following injury for investigating alterations in the gut microbiome. Alterations of the gut microbiota composition after traumatic brain injury are determined using 16S-rDNA sequencing. This protocol provides an effective method for studying the relationships between enteric microorganisms and traumatic brain injury.

11.
Redox Biol ; 28: 101322, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605963

RESUMO

Homocysteine-Methionine (HM) cycle produces universal methyl group donor S-adenosylmethione (SAM), methyltransferase inhibitor S-adenosylhomocysteine (SAH) and homocysteine (Hcy). Hyperhomocysteinemia (HHcy) is established as an independent risk factor for cardiovascular disease (CVD) and other degenerative disease. We selected 115 genes in the extended HM cycle (31 metabolic enzymes and 84 methyltransferases), examined their protein subcellular location/partner protein, investigated their mRNA levels and mapped their corresponding histone methylation status in 35 disease conditions via mining a set of public databases and intensive literature research. We have 6 major findings. 1) All HM metabolic enzymes are located only in the cytosol except for cystathionine-ß-synthase (CBS), which was identified in both cytosol and nucleus. 2) Eight disease conditions encountered only histone hypomethylation on 8 histone residues (H3R2/K4/R8/K9/K27/K36/K79 and H4R3). Nine disease conditions had only histone hypermethylation on 8 histone residues (H3R2/K4/K9/K27/K36/K79 and H4R3/K20). 3) We classified 9 disease types with differential HM cycle expression pattern. Eleven disease conditions presented most 4 HM cycle pathway suppression. 4) Three disease conditions had all 4 HM cycle pathway suppression and only histone hypomethylation on H3R2/K4/R8/K9/K36 and H4R3. 5) Eleven HM cycle metabolic enzymes interact with 955 proteins. 6) Five paired HM cycle proteins interact with each other. We conclude that HM cycle is a key metabolic sensor system which mediates receptor-independent metabolism-associated danger signal recognition and modulates SAM/SAH-dependent methylation in disease conditions and that hypomethylation on frequently modified histone residues is a key mechanism for metabolic disorders, autoimmune disease and CVD. We propose that HM metabolism takes place in the cytosol, that nuclear methylation equilibration requires a nuclear-cytosol transfer of SAM/SAH/Hcy, and that Hcy clearance is essential for genetic protection.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 226: 117608, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31605971

RESUMO

A new Schiff-base 1 based on 4-N,N-dimethylaminoaniline salicylaldehyde is developed. It possesses unique solution-solid dual emission behaviour with emission color: an aggregation-induced bright turquoise emission in liquid and strong near-infrared emission in the solid state. Interestingly, on the one hand, compound 1 is promising a ratiometric fluorescent probe for Zn2+ ions detection in the aqueous solution with high sensitivity, selectivity, and relatively low detection limit. On the other hand, based on its inner stimuli-responsive nature, outstanding thermostability and photostability, 1 should be a very promising candidate for the write-once read-many optical data storage medium.

13.
Phys Med Biol ; 64(21): 215017, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31561244

RESUMO

Lowering either the administered activity or scan time is desirable in PET imaging as it decreases the patient's radiation burden or improves patient comfort and reduces motion artifacts. But reducing these parameters lowers overall photon counts and increases noise, adversely impacting image contrast and quantification. To address this low count statistics problem, we propose a cycle-consistent generative adversarial network (Cycle GAN) model to estimate diagnostic quality PET images using low count data. Cycle GAN learns a transformation to synthesize diagnostic PET images using low count data that would be indistinguishable from our standard clinical protocol. The algorithm also learns an inverse transformation such that cycle low count PET data (inverse of synthetic estimate) generated from synthetic full count PET is close to the true low count PET. We introduced residual blocks into the generator to catch the differences between low count and full count PET in the training dataset and better handle noise. The average mean error and normalized mean square error in whole body were -0.14% ± 1.43% and 0.52% ± 0.19% with Cycle GAN model, compared to 5.59% ± 2.11% and 3.51% ± 4.14% on the original low count PET images. Normalized cross-correlation is improved from 0.970 to 0.996, and peak signal-to-noise ratio is increased from 39.4 dB to 46.0 dB with proposed method. We developed a deep learning-based approach to accurately estimate diagnostic quality PET datasets from one eighth of photon counts, and has great potential to improve low count PET image quality to the level of diagnostic PET used in clinical settings.

14.
Phys Med Biol ; 64(20): 205022, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31487698

RESUMO

The purpose of this work is to validate the application of a deep learning-based method for pelvic synthetic CT (sCT) generation that can be used for prostate proton beam therapy treatment planning. We propose to integrate dense block minimization into 3D cycle-consistent generative adversarial networks (cycleGAN) framework to effectively learn the nonlinear mapping between MRI and CT pairs. A cohort of 17 patients with co-registered CT and MR pairs were used to test the deep learning-based sCT generation method by leave-one-out cross-validation. Image quality between the sCT and CT images, gamma analysis passing rate, dose-volume metrics, distal range displacement, and the individual pencil beam Bragg peak shift between sCT- and CT-based proton plans were evaluated. The average mean absolute error (MAE) was 51.32 ± 16.91 HU. The relative differences of the statistics of the PTV dose-volume histogram (DVH) metrics in between sCT and CT were generally less than 1%. Mean values of dose difference, absolute dose difference (in percent of the prescribed dose) were -0.07% ± 0.07% and 0.23% ± 0.08%. Mean gamma analysis pass rate of 1 mm/1%, 2 mm/2%, 3 mm/3% criteria with 10% dose threshold were 92.39% ± 5.97%, 97.95% ± 2.95% and 98.97% ± 1.62% respectively. The median, mean and standard deviation of absolute maximum range differences were 0.09 cm and 0.23 ± 0.25 cm. The median and mean Bragg peak shifts among the 17 patients were 0.09 cm and 0.18 ± 0.07 cm. The image similarity, dosimetric and distal range agreement between sCT and original CT suggests the feasibility of further development of an MRI-only workflow for prostate proton radiotherapy.

15.
Eur Radiol ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31385045

RESUMO

OBJECTIVES: To evaluate the predictive value of CT radiomics features derived from the primary tumor in discriminating occult peritoneal metastasis (PM) in advanced gastric cancer (AGC). METHODS: Preoperative CT images of 233 patients with AGC were retrospectively analyzed. The region of interest (ROI) was manually drawn along the margin of the lesion on the largest slice of venous CT images, and a total of 539 quantified features were extracted automatically. The intra-class correlation coefficient (ICC) and the absolute correlation coefficient (ACC) were calculated for selecting influential features. A multivariate logistic regression model was constructed based on the training cohort, and the testing cohort validated the reliability of the model. Additionally, another model based on the preoperative clinic-pathological features was also developed. The comparison of the diagnostic performance between the two models was performed using ROC analysis and the Akaike information criterion (AIC) value. RESULTS: Six radiomics features (ID_Energy, LoG(0.5)_Energy, Compactness2, Max Diameter, Orientation, and Surface Area Density) differed significantly between AGCs with and without PM and performed well in distinguishing AGCs with PM from those without PM in the primary cohort (AUC = 0.618-0.658). The radiomics model showed a higher AUC value than each single radiomics feature in the primary cohort (0.741 vs. 0.618-0.658) and similar diagnosis performance in the validation cohort. The radiomics model showed slightly worse diagnostic efficacy than the clinic-pathological model (AUC, 0.724 vs. 0.762). CONCLUSION: Venous CT radiomics analysis based on the primary tumor provided valuable information for predicting occult PM in AGCs. KEY POINTS: • Venous CT radiomics analysis provided valuable information for predicting occult peritoneal metastases in advanced gastric cancer. • CT-based T stage was an independent predictive factor of occult peritoneal metastases in advanced gastric cancer. • A radiomics model showed slightly worse diagnostic efficacy than a clinic-pathological model.

16.
Medicine (Baltimore) ; 98(33): e16751, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415372

RESUMO

BACKGROUND: Biomechanical studies have demonstrated that cortical bone trajectory (CBT) screw can provide a 30% increase in uniaxial yield pullout load than pedicle screw (PS). In addition, the insertion torque of CBT screw is 1.71 times higher than that of PS. A meta-analysis was conducted to evaluate clinical results between CBT screw technique and PS technique in lumbar fusion surgery. METHODS: An extensive search of literature was performed in PubMed, Embase, the Cochrane library. The following outcomes were extracted: visual analog scale (VAS), Oswestry disabilities index (ODI), Japanese Orthopaedic Association (JOA) score, complications, fusion rates, hospital stay, incision length, blood loss, and operation time. Data analysis was conducted with RevMan 5.3 and STATA 12.0. RESULTS: A total of 12 studies were included in the final analysis. The results indicated that CBT group with less blood loss [P < .01], less hospital stay [P < .01], and less incision length [P < .01] than PS group. There were no significant differences between 2 groups in other clinical parameters and outcomes. CONCLUSION: CBT technique provided similar clinical outcomes and fusion rates compared to PS technique in lumbar fusion surgery. However, CBT technique provided additional benefits of less blood loss, less hospital stay, and less incision length.


Assuntos
Parafusos Ósseos , Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares , Fusão Vertebral/métodos , Fenômenos Biomecânicos , Humanos , Resultado do Tratamento
17.
Nutrients ; 11(8)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394758

RESUMO

Diet and microbiota each have a direct impact on many chronic, inflammatory, and metabolic diseases. As the field develops, a new perspective is emerging. The effects of diet may depend on the microbiota composition of the intestine. A diet that is rich in choline, red meat, dairy, or egg may promote the growth, or change the composition, of microbial species. The microbiota, in turn, may produce metabolites that increase the risk of cardiovascular disease. This article reviews our current understanding of the effects of the molecule trimethylamine-N-oxide (TMAO) obtained from food or produced by the microbiota. We review the mechanisms of actions of TMAO, and studies that associate it with cardiovascular and chronic kidney diseases. We introduce a novel concept: TMAO is one among a group of selective uremic toxins that may rise to high levels in the circulation or accumulate in various organs. Based on this information, we evaluate how TMAO may harm, by exacerbating inflammation, or may protect, by attenuating amyloid formation, in autoimmune diseases such as rheumatoid arthritis.

18.
Redox Biol ; 26: 101284, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31400697

RESUMO

Accumulated evidence strongly indicates that oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and antioxidants in favor of oxidants, plays an important role in disease pathogenesis. However, ROS can act as signaling molecules and fulfill essential physiological functions at basal levels. Each ROS would be different in the extent to stimulate and contribute to different pathophysiological effects. Importantly, multiple ROS generators can be activated either concomitantly or sequentially by relevant signaling molecules for redox biological functions. Here, we summarized the current knowledge related to chemical and biochemical features of primary ROS species and corresponding antioxidants. Metabolic pathways of five major ROS generators and five ROS clearance systems were described, including their ROS products, specific ROS enriched tissue, cell and organelle, and relevant functional implications. We provided an overview of ROS generation and induction at different levels of metabolism. We classified 11 ROS species into three types based on their reactivity and target selectivity and presented ROS homeostasis and functional implications in pathological and physiological status. This article intensively reviewed and refined biochemical basis, metabolic signaling and regulation, functional insights, and provided guidance for the identification of novel therapeutic targets.

19.
J Chem Phys ; 151(4): 044708, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31370548

RESUMO

Molybdenum trioxide (α-MoO3) is a key component in the redox solid catalysts for methane activation. The wide range of interactions including van der Waals interaction and chemical bonding in α-MoO3 as well as between methane and the catalyst surface makes the accurate description of the methane chemistry a challenge. Herein, we performed a strongly constrained and appropriately normed (SCAN)-functional based density functional theory study of the surface chemistry and reactivity of α-MoO3 toward C-H bond activation of methane. With this meta-generalized-gradient approximation functional, we can predict the bulk structure of α-MoO3 more accurately while reproducing the thermal chemistry of MoO3. The results indicate that surface reduction of α-MoO3 (010) occurs preferably through releasing the terminal oxygen atoms, generating oxygen vacancies while exposing reduced Mo centers. These oxygen vacancies tend to be separated from each other at a higher density due to repulsive interactions. Furthermore, the reduced α-MoO3 (010) promotes methane activation kinetically by reducing the activation barrier for the break of the first C-H bond and thermodynamically by stabilizing the product state as compared with those on the stoichiometric surface. There is a synergy between the reduced Mo active site and surface lattice oxygen for C-H bond cleavage. Our results also show that the reactivity based on the Perdew-Burke-Ernzerhof functional is qualitatively consistent with that from the SCAN functional.

20.
Anal Chem ; 91(16): 10894-10900, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31331163

RESUMO

Acrylate has been widely used as the recognition unit for Cys fluorescent probes. Despite this widespread use, a potential drawback of this probe type is that the ester linkage between the fluorophore and acryloyl recognition unit is liable to be hydrolyzed by abundant esterase in the cytosol, thus affording a high background signal. To solve this problem, we herein put forward a new strategy to construct a selective fluorescent probe for cysteine (Cys)/homocysteine (Hcy) with propynamide as the recognition moiety. The free probe CPA displays weakly fluorescent emission in aqueous media because of the donor-excited photoinduced electron transfer (d-PET) process within the molecule. The Michael addition of Cys (or Hcy) thiols to the conjugated alkyne of CPA gives the expected ß-sulfido-α,ß-unsaturated amides (1a/1b), which subsequently undergo an intramolecular S,N rearrangement, yielding ß-amino-α,ß-unsaturated amides (2a/2b) as the final products. The above cascade reaction results in the blockage of d-PET within CPA, thus affording a dramatic fluorescence enhancement at 495 nm. The involvement of the sulfhydryl and the adjacent amino groups in the sensing process renders CPA high selectivity for Cys/Hcy over glutathione as well as other amino acids. The probe has been successfully applied to image Cys in different cell lines. Further, CPA shows two-photon fluorescence properties, and its ability to monitor Cys in deep tissues has been demonstrated by using two-photon microscopy.

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