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1.
Artigo em Inglês | MEDLINE | ID: mdl-34464275

RESUMO

Visible-Infrared person reidentification (VI-ReID) is a challenging matching problem due to large modality variations between visible and infrared images. Existing approaches usually bridge the modality gap with only feature-level constraints, ignoring pixel-level variations. Some methods employ a generative adversarial network (GAN) to generate style-consistent images, but it destroys the structure information and incurs a considerable level of noise. In this article, we explicitly consider these challenges and formulate a novel spectrum-aware feature augmentation network named SFANet for cross-modality matching problem. Specifically, we put forward to employ grayscale-spectrum images to fully replace RGB images for feature learning. Learning with the grayscale-spectrum images, our model can apparently reduce modality discrepancy and detect inner structure relations across the different modalities, making it robust to color variations. At feature level, we improve the conventional two-stream network by balancing the number of specific and sharable convolutional blocks, which preserve the spatial structure information of features. Additionally, a bidirectional tri-constrained top-push ranking loss (BTTR) is embedded in the proposed network to improve the discriminability, which efficiently further boosts the matching accuracy. Meanwhile, we further introduce an effective dual-linear with batch normalization identification (ID) embedding method to model the identity-specific information and assist BTTR loss in magnitude stabilizing. On SYSU-MM01 and RegDB datasets, we conducted extensively experiments to demonstrate that our proposed framework contributes indispensably and achieves a very competitive VI-ReID performance.

2.
Biomed Res Int ; 2021: 4873678, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337013

RESUMO

LIHC (liver hepatocellular carcinoma) mostly occurs in patients with chronic liver disease. It is primarily induced by a vicious cycle of liver injury, inflammation, and regeneration that usually last for decades. The G protein nucleolar 2 (GNL2), as a protein-encoding gene, is also known as NGP1, Nog2, Nug2, Ngp-1, and HUMAUANTIG. Few reports are shown towards the specific biological function of GNL2. Meanwhile, it is still unclear whether it is related to the pathogenesis of carcinoma up to date. Here, our study attempts to validate the role and function of GNL2 in LIHC via multiple databases and functional assays. After analysis of gene expression profile from The Cancer Genome Atlas (TCGA) database, GNL2 was largely heightened in LIHC, and its overexpression displayed a close relationship with different stages and poor prognosis of carcinoma. After enrichment analysis, the data revealed that the genes coexpressed with GNL2 probably participated in ribosome biosynthesis which was essential for unrestricted growth of carcinoma. Cell functional assays presented that GNL2 knockdown by siRNA in LIHC cells MHCC97-H and SMCC-7721 greatly reduced cell proliferation, migration, and invasion ability. All in all, these findings capitulated that GNL2 could be a promising treatment target and prognosis biomarker for LIHC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Proteínas de Ligação ao GTP/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Prognóstico , Reprodutibilidade dos Testes , Transdução de Sinais/genética
3.
Theranostics ; 11(17): 8379-8395, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34373748

RESUMO

Growth disorders in the orofacial bone development process may lead to orofacial deformities. The balance between bone matrix formation by mesenchymal lineage osteoblasts and bone resorption by osteoclasts is vital for orofacial bone development. Although the mechanisms of orofacial mesenchymal stem cells (OMSCs) in orofacial bone development have been studied intensively, the communication between OMSCs and osteoclasts remains largely unclear. Methods: We used a neural crest cell-specific knockout mouse model to investigate orofacial bone development in GATA-binding protein 4 (GATA4) morphants. We investigated the underlying mechanisms of OMSCs-derived exosomes (OMExos) on osteoclastogenesis and bone resorption activity in vitro. miRNAs were extracted from OMExos, and differences in miRNA abundances were determined using an Affymetrix miRNA array. Luciferase reporter assays were used to validate the binding between GATA4 and miR-206-3p in OMSCs and to confirm the putative binding of miR-206-3p and its target genes in OMSCs and osteoclasts. The regulatory mechanism of the GATA4-miR-206-3p axis in OMSC osteogenic differentiation and osteoclastogenesis was examined in vitro and in vivo. Results: Wnt1-Cre;Gata4fl/fl mice (cKO) not only presented inhibited bone formation but also showed active bone resorption. Osteoclasts cocultured in vitro with cKO OMSCs presented an increased capacity for osteoclastogenesis, which was exosome-dependent. Affymetrix miRNA array analysis showed that miR-206-3p was downregulated in exosomes from shGATA4 OMSCs. Moreover, the transcriptional activity of miR-206-3p was directly regulated by GATA4 in OMSCs. We further demonstrated that miR-206-3p played a key role in the regulation of orofacial bone development by directly targeting bone morphogenetic protein-3 (Bmp3) and nuclear factor of activated T -cells, cytoplasmic 1 (NFATc1). OMExos and agomiR-206-3p enhanced bone mass in Wnt1-cre;Gata4fl/fl mice by augmenting trabecular bone structure and decreasing osteoclast numbers. Conclusion: Our findings confirm that miR-206-3p is an important downstream factor of GATA4 that regulates the functions of OMSCs and osteoclasts. These results demonstrate the efficiency of OMExos and microRNA agomirs in promoting bone regeneration, which provide an ideal therapeutic tool for orofacial bone deformities in the future.

4.
Org Biomol Chem ; 19(16): 3601-3610, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33908578

RESUMO

The zinc salt-catalyzed reduction of α-aryl imino esters, diketones and phenylacetylenes with water as hydrogen source and zinc as reductant was successfully conducted. The presented method provides a low-cost, environmentally friendly and practical preparation of α-aryl amino esters, α-hydroxyketones and phenylethylenes. By using D2O as deuterium source, the corresponding products were obtained in high efficiency with excellent deuterium incorporation rate, which gives a cheap and safe tool for access to valuable deuterium-labelled compounds.

5.
Theranostics ; 11(9): 4316-4334, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754063

RESUMO

Trio is a unique member of the Rho-GEF family that has three catalytic domains and is vital for various cellular processes in both physiological and developmental settings. TRIO mutations in humans are involved in craniofacial abnormalities, in which patients present with mandibular retrusion. However, little is known about the molecular mechanisms of Trio in neural crest cell (NCC)-derived craniofacial development, and there is still a lack of direct evidence to assign a functional role to Trio in NCC-induced craniofacial abnormalities. Methods: In vivo, we used zebrafish and NCC-specific knockout mouse models to investigate the phenotype and dynamics of NCC development in Trio morphants. In vitro, iTRAQ, GST pull-down assays, and proximity ligation assay (PLA) were used to explore the role of Trio and its potential downstream mediators in NCC migration and differentiation. Results: In zebrafish and mouse models, disruption of Trio elicited a migration deficit and impaired the differentiation of NCC derivatives, leading to craniofacial growth deficiency and mandibular retrusion. Moreover, Trio positively regulated Myh9 expression and directly interacted with Myh9 to coregulate downstream cellular signaling in NCCs. We further demonstrated that disruption of Trio or Myh9 inhibited Rac1 and Cdc42 activity, specifically affecting the nuclear export of ß-catenin and NCC polarization. Remarkably, craniofacial abnormalities caused by trio deficiency in zebrafish could be partially rescued by the injection of mRNA encoding myh9, ca-Rac1, or ca-Cdc42. Conclusions: Here, we identified that Trio, interacting mostly with Myh9, acts as a key regulator of NCC migration and differentiation during craniofacial development. Our results indicate that trio morphant zebrafish and Wnt1-cre;Triofl/fl mice offer potential model systems to facilitate the study of the pathogenic mechanisms of Trio mutations causing craniofacial abnormalities.


Assuntos
Cadeias Pesadas de Miosina/genética , Crista Neural/fisiologia , Animais , Diferenciação Celular/genética , Linhagem Celular , Movimento Celular/genética , Embrião de Mamíferos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Fenótipo , RNA Mensageiro/genética , Transdução de Sinais/genética , Peixe-Zebra , beta Catenina/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-33606630

RESUMO

This paper proposes an end-to-end learnt lossy image compression approach, which is built on top of the deep nerual network (DNN)-based variational auto-encoder (VAE) structure with Non-Local Attention optimization and Improved Context modeling (NLAIC). Our NLAIC 1) embeds non-local network operations as non-linear transforms in both main and hyper coders for deriving respective latent features and hyperpriors by exploiting both local and global correlations, 2) applies attention mechanism to generate implicit masks that are used to weigh the features for adaptive bit allocation, and 3) implements the improved conditional entropy modeling of latent features using joint 3D convolutional neural network (CNN)-based autoregressive contexts and hyperpriors. Towards the practical application, additional enhancements are also introduced to speed up the computational processing (e.g., parallel 3D CNN-based context prediction), decrease the memory consumption (e.g., sparse non-local processing) and reduce the implementation complexity (e.g., a unified model for variable rates without re-training). The proposed model outperforms existing learnt and conventional (e.g., BPG, JPEG2000, JPEG) image compression methods, on both Kodak and Tecnick datasets with the state-of-the-art compression efficiency, for both PSNR and MS-SSIM quality measurements. We have made all materials publicly accessible at https://njuvision.github.io/NIC for reproducible research.

7.
J BUON ; 25(5): 2510-2514, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33277876

RESUMO

PURPOSE: Retinoblastoma causes significant human mortality especially in children. Although retinoblastoma may be treated if detected at early stage, however, it becomes destructive at advanced stages. The treatment involves surgery and chemotherapy. However, the chemotherapeutic agents have severe adverse effects. Therefore, development of viable drugs and identification of novel molecular therapeutic targets may enable efficient management of retinoblastoma. This study was designed to examine the expression profile of Chromatin Assembly Factor-1 (CHAF1A) and explore its therapeutic implications in retinoblastoma. METHODS: The expression of CHAF1A was determined by qRT-PCR. MTT assay was used for the determination of the cell viability. Apoptosis was detected by acridine orange (AO)/ethidium bromide (EB) and annexin V/propidium iodide (PI) assay. Cell cycle analysis was determined by flow cytometery. Protein expression was determined by western blot analysis. RESULTS: The results showed that CHAF1A is significantly upregulated in human retinoblastoma, with 7.3 folds upregulation in retinoblastoma cells relative to normal cells. Knockdown of CHAF1A resulted in significant decline in the viability of the RB355 retinoblastoma cells. The flow cytometric analysis showed that knockdown of CHAF1A caused arrest of the RB355 cells at G0/G1 phase of the cell cycle. This was also linked with significant downregulation of cyclin D1 and cyclin E1. The AO/EB staining assay showed that CHAF1A knockdown promotes apoptosis which is associated with downregulation of Bcl-2 and upregulation of Bax. CONCLUSION: Taken together, these results suggest that CHAF1A is upregulated in retinoblastoma and regulates its proliferation and apoptosis. As such CHAF1A may act as biomarker as well as therapeutic target for the management of retinoblastoma.

8.
Sci Total Environ ; 749: 141571, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33370894

RESUMO

Precipitation is a key factor affecting shallow water table fluctuations. Although the literature on shallow aquifers is vast, groundwater response to precipitation in peatlands has received little attention so far. Characterizing groundwater response to precipitation events in differently managed peatlands can give insight into ecohydrological processes. In this study we determined the groundwater table response rate following precipitation events at a drained and a rewetted fen to characterize the effect of rewetting on hydrological buffer capacity. Multiple regression analysis revealed that the groundwater table at the rewetted fen has more than two times lower rate of response to precipitation events than that of the drained fen, even after adjusting for antecedent groundwater levels. Thus, the rewetted fen delivers a better hydrological buffer function against heavy precipitation events than the drained fen. We found that for the depths at which the groundwater interacts with incoming precipitation, the peat of the rewetted fen has a higher specific yield causing groundwater to rise slower compared to the response at the drained fen. A period of 20 years of rewetting was sufficient to form a new layer of organic material with a significant fraction of macropores providing storage capacity. Long-term rewetting has the potential to create favorable conditions for new peat accumulation, thereby altering water table response. Our study has implications for evaluating the success of restoration measures with respect to hydrological functions of percolation fens.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33175187

RESUMO

Ocean acidification and microplastic pollution is a global environmental threat, this research evaluated the effects of ocean acidification and microplastics on mussel digestive tract microbial community. The 16S rRNA gene was sequenced to characterize the flora. Species diversity in the samples was assessed by clustering valid tags on 97% similarity. Bacteroidetes, Firmicutes and Proteobacteria were the three most abundant genera in the four groups, with Bacteroidetes showing the highest diversity. However, no differences in flora structure were evident under various treatments. Phylogenetic relationship analysis revealed Bacteroidetes and Firmicutes had the highest OTU diversity. The weighted UniFrac distance, principal coordinate analysis (PCoA), unweighted pair group method with arithmetic mean (UPGMA) cluster tree and analysis of molecular variance (AMOVA) evaluation results for all samples also showed that changes in pH and microplastics concentration did not significantly affect the microbial community structure in the mussel digestive tract. The results presented the no significant effects of ocean acidification and microplastics intake on mussel intestinal diversity.

10.
Exp Cell Res ; 396(1): 112265, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32898553

RESUMO

Many bone diseases result from abnormal bone resorption by osteoclasts (OCs). Studying OC related regulatory genes is necessary for the development of new therapeutic strategies. Rho GTPases have been proven to regulate OC differentiation and function and only mature OCs can carry out bone resorption. Here we demonstrate that Rac1 and Cdc42 exchange factor Triple functional domain (Trio) is critical for bone resorption caused by OCs. In this study, we created LysM-Cre;Triofl/fl conditional knockout mice in which Trio was conditionally ablated in monocytes. LysM-Cre;Triofl/fl mice showed increased bone mass due to impaired bone resorption caused by OCs. Furthermore, our in vitro analysis indicated that Trio conditional deficiency significantly suppressed OC differentiation and function. At the molecular level, Trio deficiency significantly inhibited the expression of genes critical for osteoclastogenesis and OC function. Mechanistically, our researches suggested that perturbed Rac1/Cdc42-PAK1-ERK/p38 signaling could be used to explain the lower ability of bone resorption in CKO mice. Taken together, this study indicates that Trio is a regulator of OCs. Studying the role of Trio in OCs provides a potential new insight for the treatment of OC related bone diseases.


Assuntos
Reabsorção Óssea/genética , Fêmur/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Neuropeptídeos/genética , Osteoclastos/metabolismo , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinases/genética , Proteína cdc42 de Ligação ao GTP/genética , Proteínas rac1 de Ligação ao GTP/genética , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Feminino , Fêmur/citologia , Fêmur/efeitos dos fármacos , Regulação da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/deficiência , Fator Estimulador de Colônias de Macrófagos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Neuropeptídeos/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Fosfoproteínas/deficiência , Proteínas Serina-Treonina Quinases/deficiência , Ligante RANK/farmacologia , Transdução de Sinais , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo
11.
Nanoscale ; 12(27): 14788-14800, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32627781

RESUMO

Angiogenesis is an irreplaceable therapeutic cancer target, where anti-angiogenesis are drugs that are limited by their hydrophobicity and low therapeutic effects. What is more, the long-term shutdown of tumor blood vessel density also aggravates hypoxia and causes immunosuppression in the tumor microenvironment (TME). In order to solve these shortcomings, we developed a single therapeutic agent based on a bovine serum albumin nanocarrier that can co-deliver the anti-angiogenic drug Sorafenib ("S") and the photosensitizer Ce6 ("C") along with a molecular oxygen supply based on MnO2 ("M") as a convenient one-pot formulated nanoscale agent (SCM@BSA). Compared with anti-angiogenesis monotherapy, SCM@BSA can not only improve upon the solubility and therapeutic effects of anti-angiogenesis agents, but it also reshapes the immunosuppressive TME during anti-angiogenic therapy. Together, these results point out that SCM@BSA synthesized via a very simple method can solve the shortcomings usually experienced during long-term anti-angiogenic therapy.


Assuntos
Fotoquimioterapia , Imunossupressão , Compostos de Manganês , Óxidos , Oxigênio
12.
Sensors (Basel) ; 20(12)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575436

RESUMO

The research of robotic autonomous radioactivity detection or radioactive source search plays an important role in the monitoring and disposal of nuclear safety and biological safety. In this paper, a method for autonomously searching for radioactive sources through mobile robots was proposed. In the method, by using a partially observable Markov decision process (POMDP), the search of autonomous unknown radioactive sources was realized according to a series of radiation information measured by mobile robot. First, the factors affecting the accuracy of radiation measurement during the robot's movement were analyzed. Based on these factors, the behavior set of POMDP was designed. Secondly, the parameters of the radioactive source were estimated in the Bayesian framework. In addition, through the reward strategy, autonomous navigation of the robot to the position of the radiation source was achieved. The search algorithm was simulated and tested, and the TurtleBot robot platform was used to conduct a real search experiment on the radio source Cs-137 with an activity of 37 MBq indoors. The experimental results showed the effectiveness of the method. Additionally, from the experiments, it could been seen that the robot was affected by the linear velocity, angular velocity, positioning accuracy and the number of measurements in the process of autonomous search for the radioactive source. The proposed mobile robot autonomous search method can be applied to the search for lost radioactive sources, as well as for the leakage of substances (nuclear or chemical) in nuclear power plants and chemical plants.

13.
Curr Microbiol ; 77(8): 1890-1895, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32356168

RESUMO

In this study, a wild-type Pseudomonas aeruginosa strain KT1115 with the capability of converting rapeseed oils into di-rhamnolipids, a class of biosurfactants with extensive application potential, was successfully isolated and characterized. Di-rhamnolipids production by microorganism culture provided a mild, eco-friendly, and secure approach for surfactants production instead of conventional chemical synthesis. However, few studies have been attempted to explore the metabolic mechanism behind the high di-rhamnolipids production by P. aeruginosa. Here, we presented the graft genome of a wild-type P. aeruginosa strain KT1115, with emphasis on the analysis of oils metabolism and rhamnolipid synthesis. The availability of the genome sequence provides additional insight into the genetic mechanism enhancing di-rhamnolipids biosynthesis.


Assuntos
Genoma Bacteriano , Glicolipídeos/biossíntese , Redes e Vias Metabólicas/genética , Pseudomonas aeruginosa/genética , Óleo de Brassica napus/metabolismo , Pseudomonas aeruginosa/metabolismo , Tensoativos/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-32248090

RESUMO

This paper presents a dual camera system for high spatiotemporal resolution (HSTR) video acquisition, where one camera shoots a video with high spatial resolution and low frame rate (HSR-LFR) and another one captures a low spatial resolution and high frame rate (LSR-HFR) video. Our main goal is to combine videos from LSR-HFR and HSR-LFR cameras to create an HSTR video. We propose an end-to-end learning framework, AWnet, mainly consisting of a FlowNet and a FusionNet that learn an adaptive weighting function in pixel domain to combine inputs in a frame recurrent fashion. To improve the reconstruction quality for cameras used in reality, we also introduce noise regularization under the same framework. Our method has demonstrated noticeable performance gains in terms of both objective PSNR measurement in simulation with different publicly available video and light-field datasets and subjective evaluation with real data captured by dual iPhone 7 and Grasshopper3 cameras. Ablation studies are further conducted to investigate and explore various aspects (such as reference structure, camera parallax, exposure time, etc) of our system to fully understand its capability for potential applications.

15.
Sensors (Basel) ; 20(6)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178238

RESUMO

LiDAR sensors can provide dependable 3D spatial information at a low frequency (around 10 Hz) and have been widely applied in the field of autonomous driving and unmanned aerial vehicle (UAV). However, the camera with a higher frequency (around 20 Hz) has to be decreased so as to match with LiDAR in a multi-sensor system. In this paper, we propose a novel Pseudo-LiDAR interpolation network (PLIN) to increase the frequency of LiDAR sensor data. PLIN can generate temporally and spatially high-quality point cloud sequences to match the high frequency of cameras. To achieve this goal, we design a coarse interpolation stage guided by consecutive sparse depth maps and motion relationship. We also propose a refined interpolation stage guided by the realistic scene. Using this coarse-to-fine cascade structure, our method can progressively perceive multi-modal information and generate accurate intermediate point clouds. To the best of our knowledge, this is the first deep framework for Pseudo-LiDAR point cloud interpolation, which shows appealing applications in navigation systems equipped with LiDAR and cameras. Experimental results demonstrate that PLIN achieves promising performance on the KITTI dataset, significantly outperforming the traditional interpolation method and the state-of-the-art video interpolation technique.

16.
Phys Chem Chem Phys ; 22(7): 4115-4121, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32031551

RESUMO

The aerogen bond between the Xe and chalcogen atoms in complexes pairing XeOF2 with R1YR2 is examined by ab initio calculations for Y = O, S, and Se. In addition to HYH, one or both H atoms are changed to F or methyl groups. The interaction energies are strong, varying between 21 and 54 kJ mol-1. The aerogen bond is composed of roughly half electrostatic attraction, with lesser contributions due to polarization and dispersion. Replacement of H by electron-withdrawing F on the base weakens the interaction, while electron releasing Me substituents have the opposite effect. Whereas the aerogen bonds are stronger for O than for S or Se for HYH, HYF, and MeYH, it is the heavier chalcogen atoms that form the stronger dimers for MeOF and MeOMe. These trends cannot be fully explained by molecular electrostatic potentials or by measures of charge transfer, nor are they entirely consistent with electron density topology.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31620431

RESUMO

Actinobacillus succinogenes is one of the most promising strains for succinic acid production; however, the lack of efficient genetic tools for strain modification development hinders its further application. In this study, a markerless knockout method for A. succinogenes using in-frame deletion was first developed. The resulting ΔpflA (encode pyruvate formate lyase 1-activating protein) strain displayed distinctive organic acid synthesis capacity under different cultivation modes. Additional acetate accumulation was observed in the ΔpflA strain relative to that of the wild type under aerobic conditions, indicating that acetate biosynthetic pathway was activated. Importantly, pyruvate was completely converted to lactate under anaerobic fermentation. The transcription analysis and enzyme assay revealed that the expression level and specific activity of lactate dehydrogenase (LDH) were significantly increased. In addition, the mRNA expression level of ldh was nearly increased 85-fold compared to that of the wild-type strain during aerobic-anaerobic dual-phase fermentation, resulting in 43.05 g/L lactate. These results demonstrate that pflA plays an important role in the regulation of C3 flux distribution. The deletion of pflA leads to the improvement of acetic acid production under aerobic conditions and activates lactic acid biosynthesis under anaerobic conditions. This study will help elaborate the mechanism governing organic acid biosynthesis in A. succinogenes.

18.
ACS Nano ; 13(11): 12638-12652, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31625721

RESUMO

Photodynamic therapy (PDT) is a clinical cancer treatment modality based on the induction of therapeutic reactive oxygen species (ROS), which can trigger immunogenic cell death (ICD). With the aim of simultaneously improving both PDT-mediated intracellular ROS production and ICD levels, we designed a serum albumin (SA)-coated boehmite ("B"; aluminum hydroxide oxide) organic-inorganic scaffold that could be loaded with chlorin e6 (Ce6), a photosensitizer, and a honey bee venom melittin (MLT) peptide, denoted Ce6/MLT@SAB. Ce6/MLT@SAB was anchored by a boehmite nanorod structure and exhibited particle size of approximately 180 nm. Ce6/MLT@SAB could significantly reduce hemolysis relative to that of free MLT, while providing MLT-enhanced PDT antitumor effects in vitro. Compared with Ce6@SAB, Ce6/MLT@SAB improved Ce6 penetration of cancer cells both in vitro and in vivo, thereby providing enhanced intracellular ROS generation with 660 nm light treatment. Following phototreatment, Ce6/MLT@SAB-treated cells displayed significantly improved levels of ICD and abilities to activate dendritic cells. In the absence of laser irradiation, multidose injection of Ce6/MLT@SAB could delay the growth of subcutaneous murine tumors by more than 60%, compared to controls. When combined with laser irradiation, a single injection and phototreatment with Ce6/MLT@SAB eradicated one-third of subcutaneous tumors in treated mice. The addition of an immune checkpoint blockade to Ce6/MLT@SAB phototreatment further augmented antitumor effects, generating increased numbers of CD4+ and CD8+ T cells in tumors with concomitant reduction of myeloid-derived suppressor cells.


Assuntos
Antineoplásicos , Imunoterapia/métodos , Meliteno , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Morte Celular Imunogênica/efeitos dos fármacos , Meliteno/química , Meliteno/farmacocinética , Meliteno/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/patologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/farmacologia
19.
Med Sci Monit ; 25: 1113-1121, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30739905

RESUMO

BACKGROUND Diabetic retinopathy (DR) is a macrovascular complication that occurs in diabetic patients. Conventional treatments for the management of DR have many limitations. Thus, the present investigation evaluated the protective effect of fangchinoline against diabetic retinopathy (DR). MATERIAL AND METHODS DR was induced by streptozotocin (STZ; 60 mg/kg; i.p.) and rats were treated with fangchinoline 1, 3, and 10 mg/kg for 16 weeks. DR was confirmed by determining the concentration of advanced glycation end-products (AGEs) and morphology of retinal tissues. Parameters of oxidative stress and expression of inflammatory cytokines and receptor for advanced glycation end-products (RAGE) in the retinal tissue were determined by Western blot assay and reverse transcription polymerase chain reaction (RT-PCR). Moreover enzyme-linked immunosorbent assay (ELISA) was used to determine the apoptosis index and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the retinal tissues. RESULTS Our study reveals that the concentration of glycosylated hemoglobin (HbA1c) and glucose in the plasma and AGEs in the retinal tissue were significantly reduced in the fangchinoline group compared to the DR group. Moreover, treatment with fangchinoline attenuated the altered retinal morphology and expression of inflammatory mediators and RAGE in the retinal tissues of DR rats. There was a significant (p<0.01) decrease in oxidative stress, activity of NF-κB, and apoptosis index in the fangchinoline group compared to the DR group of rats. CONCLUSIONS Our investigation shows that fangchinoline attenuates the apoptosis of retinal cells in STZ-induced diabetic retinopathy rats by inhibiting the RAGE/NF-κB pathway.


Assuntos
Benzilisoquinolinas/farmacologia , Retinopatia Diabética/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Benzilisoquinolinas/uso terapêutico , Citocinas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Hemoglobina A Glicada , Masculino , NF-kappa B/efeitos dos fármacos , Estresse Oxidativo , Ratos , Ratos Wistar , Receptor para Produtos Finais de Glicação Avançada/efeitos dos fármacos , Retina , Transdução de Sinais
20.
BMC Complement Altern Med ; 17(1): 531, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29237430

RESUMO

BACKGROUND: Quercetin (QCT) is a flavonol present in many vegetables, it is proved to show chemo preventive effect against lung, cervical, prostate, breast and colon cancer due to its anti-inflammatory, anti-tumor and anti-oxidant property. Looking into the reported chemo-preventive effect we speculated antitumor activity in retinoblastoma (RB) Y79 cells, we also studied the molecular mechanism for antitumor activity. METHODS: The effect of QCT on Y79 cell viability count was done by cell counting kit, cell cycle distribution, apoptosis studies and mitochondrial membrane potential was evaluated by flow cytometry. Protein expression was done by western blot analysis. RESULTS: The outcomes of study showed that QCT reduced Y79 cell viability and caused arrest of G1 phase in cell cycle via decreasing the expression levels of cyclin-dependent kinase (CDK)2/6 and cyclin D3 and by increasing the levels of both CDK inhibitor proteins p21 and p27. Apoptosis of Y79 cells mediated by QCT occurred via activation of both caspases-3/-9. Flow cytometry studies showed that QCT caused collapse in mitochondrial membrane potential (ΔΨm) in Y79 cells. Western blot studies confirmed that QCT brought about phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). We also established that inhibitors of JNK and p38 MAPK suppressed QCT mediated activation of both caspases-3/-9 and subdued the apoptosis of cancerous Y79 cells. CONCLUSION: All the results of the study suggest that QCT induced the apoptosis of Y79 cells via activation of JNK and p38 MAPK pathways, providing a novel treatment approach for human RB.


Assuntos
Antineoplásicos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Quercetina/farmacologia , Retinoblastoma/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos
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