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1.
Sci Total Environ ; 753: 141961, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32889319

RESUMO

Nutrient stoichiometry and input of trace metals may profoundly affect the growth and community structure of phytoplankton. A bioassay experiment was designed to explore the key components in atmospheric deposition that affect marine phytoplankton growth by adding aerosols and analogues nutrients and Cu to the surface water of the coastal East China Sea (ECS). Our results showed that atmospheric deposition along with the input of phosphate could largely enhance the chlorophyll a (Chl a) concentrations in this eutrophic water. Phosphorus addition lifted the proportions of T. oceanica in Diatoms and B. brevisulcata in Dinoflagellates. T. oceanica replaced S. costatum and became the dominant diatom species after the Chl a peak, probably associated with the N/P ratio approaching to 16. Atmospheric aerosols containing affluent N and little P showed limited promotion to Chl a, and the positive effect was very likely due to the soluble Cu and other trace metals supplied by the aerosol. Moreover, soluble aerosol Cu was found to be conducive to the relative abundance of most dominant class Coscinodiscophyceae, and both soluble aerosol Fe and Cu seemed to be very important for increasing the proportion of S. costatum. Soluble metals could be the key components in aerosols controlling the phytoplankton composition in the eutrophic sea and such impact might exceed affluent P provided by other exogenous sources.


Assuntos
Diatomáceas , Fitoplâncton , Aerossóis/análise , China , Clorofila A
2.
J Hazard Mater ; 402: 123471, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32693336

RESUMO

Short chain carboxylic acids (SCCAs) production is one of the primary ways to recycle excess sludge (ES). However, the high cost for the SCCAs separation/extraction due to its complete miscibility in water hinders the practical application of SCCAs and the popularization of this recycling way. To overcome this barrier, this study performed an emerging chain elongation (CE) technology to upgrade the SCCAs-rich sludge fermentation broth into the highly hydrophobic medium chain carboxylic acids (MCCAs). In a continuous expanded granule sludge bed (EGSB) reactor, a maximal MCCAs yield of 67.39 % and the corresponding concentration of 9.80 g COD/L (224.97 mM C/L) were achieved. By supplying CO2 at a loading rate of 2 [Formula: see text] to lower the hydrogen partial pressure, the ethanol utilization rate and the resulting MCCAs yield were further improved. In addition, three branched-MCCAs including iso-caproate, iso-heptylate, and iso-caprylate were obtained the first time from waste biomass with the average proportions of 6.17 %, 3.65 %, and 0.8 %, respectively. The branched-MCCAs came from the CE of branched-SCCAs. The granule sludges performing CE were mainly consisted of rod-shaped cells, and dominated by Clostridium sensu stricto and Clostridium IV. This study is expected to lay a foundation for recycling ES to MCCAs.

3.
BMC Complement Med Ther ; 20(1): 341, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176782

RESUMO

BACKGROUND: Herba Siegesbeckiae (HS), the dried aerial parts of Siegesbeckia orientalis L., S. pubescens Makino, or S. glabrescens Makino, is traditionally used for treating chronic diseases in China. However, there is no information about the chronic toxicity of HS. The objective of this study is to evaluate the 24-week oral dosing toxicities of HS aqueous extract (HSE) in rats. METHODS: S. orientalis-originated HS was reflux-extracted with distilled water. Sprague-Dawley rats were randomly divided into four groups, with 10 males and 10 females in each group. The rats were intragastrically administered with HSE at 5, 1.67 and 0.56 g/kg (experimental groups) or an equal volume of distilled water (control group), 6 days a week, for 24 weeks. The high dose of HSE (5 g/kg) was its maximum tolerated dose. Body weight was recorded every 2 days during the experimental period. Chemical, hematological and histopathological parameters, as well as organ weights, were measured at the end of the experiment. RESULTS: Decreased body weight gain; increased liver and lung relative weights; histopathological alterations in liver and lung tissues; elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were found after HSE treatments. In liver tissues, HSE treatment upregulated levels of three pro-inflammatory cytokines: IL-6, IL-1ß and TNF-α. In lung tissues, HSE treatment caused oxidative stress and activated mitogen-activated protein kinases (MAPKs). CONCLUSION: Long-term oral administration of HSE caused toxicities in rats evidenced by decreased body weight gain, as well as liver and lung damage. Treatment-induced oxidative stress, inflammation and MAPK activation are involved in HSE's toxicities. Caution should be taken when using HS to treat chronic diseases.

4.
J Biosci ; 452020.
Artigo em Inglês | MEDLINE | ID: mdl-33184245

RESUMO

Modeling a protein functional network in concerned species is an efficient approach for identifying novel genes in certain biological pathways. Tea plant (Camellia sinensis) is an important commercial crop abundant in numerous characteristic secondary metabolites (e.g., polyphenols, alkaloids, alkaloids) that confer tea quality and health benefits. Decoding novel genes responsible for tea characteristic components is an important basis for applied genetic improvement and metabolic engineering. Herein, a high-quality protein functional network for tea plant (TeaPoN) was predicted using cross-species protein functional associations transferring and integration combined with a stringent biological network criterion control. TeaPoN contained 31,273 nonredundant functional interactions among 6,634 tea proteins (or genes), with general network topological properties such as scale-free and small-world. We revealed the modular organization of genes related to the major three tea characteristic components (theanine, caffeine, catechin) in TeaPoN, which served as strong evidence for the utility of TeaPoN in novel gene mining. Importantly, several case studies regarding gene identification for tea characteristic components were presented. To aid in the use of TeaPoN, a concise web interface for data deposit and novel gene screening was developed (http://teapon.wchoda.com). We believe that TeaPoN will serve as a useful platform for functional genomics studies associated with characteristic secondary metabolites in tea plant.

5.
Biomater Sci ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33184620

RESUMO

Wound healing is a complex and sequential biological process that involves multiple stages. Current treatments for nonhealing or chronic wounds are unsatisfactory as they exert a single effect on one specific activity. Herein, we constructed a silver nanowire (AgNW)-based, three-dimensional (3D), porous foam dressing that is flexible and conductive. This conductive foam dressing was composed of AgNWs modified with a stable hydrophobic coating and porous polyurethane (PU), providing a skeleton to support the 3D conductive networks. The AgNWs-PU foam dressing exhibited favorable biocompatibility, outstanding electrical properties, excellent bending-compression durability, and long-term stability under wet conditions, making it suitable for wound treatment. Via the conductive foam dressing, negative pressure and exogenous wound directional electric fields (EFs) could be integrated for simultaneous implementation, and the artificial jointly constructed microenvironment promoted wound healing in a system. This novel "all-in-one" device presented intrinsic multifunctionality, including the drainage of pus and necrotic tissue, mitigation of inflammation, promotion of cell proliferation, direction of keratinocyte migration, and induction of angiogenesis. An immunohistochemical assay and western blot analysis illustrated that the angiogenesis and cell proliferation pathways in the tissue were significantly activated when this novel therapy was adopted. More importantly, the practical performance of this "all-in-one" device was demonstrated by assessment of full-thickness defect wounds in model pigs. Comparing the percentage of residual wound area after administration of traditional treatment (25.82 ± 3.52%) and the novel treatment (3.07 ± 1.23%) demonstrated the promising applications of this novel treatment in clinical wound healing.

6.
Org Lett ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175549

RESUMO

The benzylic C-H group of α,α-dicyanoolefins from 3-substituted 1-indanones could be significantly activated via transmission along the aromatic system, thus enabling dynamic kinetic resolution via a traditional reversible deprotonation-protonation process. Enantioenriched 9-substituted 9H-fluorene frameworks were finally constructed through an asymmetric vinylogous Michael addition to nitroolefins, followed by a cascade cyclization and oxidative aromatization process, under the catalysis of a chiral bifunctional thiourea-tertiary amine.

7.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120315398, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33147994

RESUMO

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a vascular degenerative disease causing sudden rupture of aorta and significant mortality in elders. Nevertheless, no prognostic and therapeutic target is available for disease management. Gal-1 (galectin-1) is a ß-galactoside-binding lectin constitutively expressed in vasculature with roles in maintaining vascular homeostasis. This study aims to investigate the potential involvement of Gal-1 in AAA progression. Approach and Results: Gal-1 was significantly elevated in circulation and aortic tissues of Ang II (angiotensin II)-infused apoE-deficient mice developing AAA. Gal-1 deficiency reduced incidence and severity of AAA with lower expression of aortic MMPs (matrix metalloproteases) and proinflammatory cytokines. TNFα (tumor necrosis factor alpha) induced Gal-1 expression in cultured vascular smooth muscle cells and adventitial fibroblasts. Gal-1 deletion enhanced TNFα-induced MMP9 expression in fibroblasts but not vascular smooth muscle cells. Cysteinyl-labeling assay demonstrated that aortic Gal-1 exhibited susceptibility to oxidation in vivo. Recombinant oxidized Gal-1 induced expression of MMP9 and inflammatory cytokines to various extents in macrophages, vascular smooth muscle cells, and fibroblasts through activation of MAP kinase signaling. Clinically, serum MMP9 level was significantly higher in both patients with AAA and coronary artery disease than in control subjects, whereas serum Gal-1 level was elevated in patients with AAA but not coronary artery disease when compared with controls. CONCLUSIONS: Gal-1 is highly induced and contributes to AAA by enhancing matrix degradation activity and inflammatory responses in experimental model. The pathological link between Gal-1 and AAA is also observed in human patients. These findings support the potential of Gal-1 as a disease biomarker and therapeutic target of AAA.

8.
Cancer Lett ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33148467

RESUMO

The acyl-CoA thioesterase (ACOT) family catalyses the hydrolysis of acyl-CoA thioesters to their corresponding non-esterified fatty acid and coenzyme A (CoA). Increasing evidence suggests that cancer cells generally have altered lipid metabolism in different aspects. However, the roles of the ACOT family in cancer, especially in pancreatic ductal carcinoma (PDAC), are largely unknown. In the present study, we mined data to determine the clinical significance of all eleven ACOT genes among nine major solid tumour types from TCGA database and found that the expression of ACOT4 in PDAC was negatively correlated with patient survival, establishing ACOT4 as a potential biomarker of PDAC. Depletion of ACOT4 attenuated the proliferation and tumour formation of PDAC cells. Using mass spectrometry, HSPA1A was found to associate with ACOT4. Furthermore, we found that phosphorylation of ACOT4 at S392 by AKT decreased the binding of ACOT4 to HSPA1A, resulting in ACOT4 accumulation. The ACOT4 elevation promotes pancreatic tumourigenesis by producing excessive CoA to support tumour cell metabolism. Thus, our study expands the relationship between AKT signalling and lipid metabolism and establishes a functional role of ACOT4 in PDAC.

9.
Anal Bioanal Chem ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33155131

RESUMO

As mercury ions (Hg2+) are emanated to surroundings in the course of various natural events and human activities, an accurate sensing of Hg2+ is essential for human health and environmental protection. Herein, a new aggregation-induced chemiluminescence (CL) sensor for fast, sensitive, and selective detection of Hg2+ is developed, based on the CL enhancement of bis(2,4,6-trichlorophenyl)oxalate (TCPO)-H2O2 system by thiolate-protected gold complexes (Au(I)-thiolate complexes) in the aggregated state. Because Hg2+ has a strong interaction with hydrosulfuryl (-SH) groups in Au(I)-thiolate complexes, the aggregation is disrupted and the CL is quenched. The decrease of CL intensity is proportional to Hg2+ contents with a linear range of 0.005-10 µg mL-1 and the limit of detection (LOD) is 3 ng mL-1. To the best of our knowledge, this is the first AIE CL sensor for Hg2+ detection. The study opens up attractive perspectives for developing simple and rapid aggregation-induced CL methods in monitoring heavy metals.

10.
Biomater Sci ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155581

RESUMO

Co-delivery of H2O2-generating agent and catalyst via a nano-Fenton reactor to the tumor acidic microenvironment for amplified tumor oxidation therapy has been widely studied. However, high side effects and low efficiency remain the limitations of the design and development of this process. Herein, a new nano-Fenton reactor in which mesoporous silica is integrated with Fe3O4 and palmitoyl ascorbate (Fe3O4@SiO2-PA) was designed, with the product exhibiting good dispersion, stability, uniformity and consistent spectral characteristics. The results show that Fe3O4@mSiO2-PA successfully enters cancer cells, significantly inhibits HeLa cells and 3D tumor spheroid growth in vitro via the induction of apoptosis. Meanwhile, Fe3O4@mSiO2-PA administration in vivo markedly suppresses HeLa tumor xenografts growth via the induction of apoptosis, followed by caspase-3 activation and cytochrome C release. Further investigation revealed that Fe3O4@mSiO2-PA causes enhanced production of reactive oxygen species (ROS), which subsequently triggers DNA damage and causes dysfunction of the MAPK and PI3K/AKT pathways. Importantly, Fe3O4@mSiO2-PA shows few side effects and good biocompatibility in vivo. Taken together, these results suggest that Fe3O4@mSiO2-PA inhibits HeLa cell growth in vitro and in vivo by triggering enhanced oxidative damage and regulating multiple signal pathways. Our findings validate the rational design that mesoporous silica integrated with Fe3O4 and palmitoyl ascorbate can act as a new nano-Fenton reactor for amplified tumor oxidation therapy.

11.
Immun Inflamm Dis ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33156578

RESUMO

OBJECTIVE: Considering the potential of adipose-derived stem cells (ADSCs) migrating towards cancer cells, this study was performed to explore the function of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) modified ADSCs on the development and progression of hepatocellular carcinoma (HCC). METHODS: ADSCs were extracted from human adipose tissues and identified through immunofluorescence and flow cytometry. Oil red staining and alizarin red staining were performed to clarify the differentiation potential of ADSCs. AAV-CMV-sTRAIL was transfected into ADSCs before Western blot and Transwell measurements. sTRAIL-ADSCs were cocultured with HCC cells to explore its effect on the proliferation and apoptosis of HCC cells. The possible effect of sTRAIL-ADSCs or ADSCs on tumor growth and metastasis was determined in vivo using xenograft nude mouse models. RESULTS: ADSCs were successfully extracted from adipose tissues, which were confirmed by cell morphology and positive expressions of CD44 and CD105. ADSCs were found with differentiation potential. After transfection, TRAIL was stably expressed in sTRAIL-ADSCs. Both ADSCs and sTRAIL-ADSCs can migrate towards HCC cells. In addition, sTRAIL-ADSCs can promote the cell apoptosis and inhibit cell proliferation in vitro, on parallel it can also suppress epithelial-mesenchymal transition, tumor growth, and metastasis in vivo. CONCLUSION: TRAIL modified ADSCs can migrate towards HCC cells to inhibit tumor growth and the metastasis of implanted HCC tumors, which hints TRAIL modified ADSCs may be a new therapeutic approach for HCC treatment.

12.
Cytokine ; 137: 155345, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33137563

RESUMO

BACKGROUND: The roles of pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress were unknown in elderly patients with recurrent ventricular arrhythmias (VA). We evaluated whether cross talk between oxidative stress, pro-inflammatory microparticles, and pro-inflammatory cytokines play the roles in elderly patients with recurrent VA after coronary stenting. This research sought to investigate the effects of oxidative stress, pro-inflammatory microparticles, and pro-inflammatory cytokines on recurrent VA in elderly patients after coronary stenting. METHODS: In this study, we included 613 consecutive elderly patients with recurrent ventricular arrhythmias induced by coronary reocclusions after coronary stenting. We measured CD31+ endothelial microparticle (CD31+EMP), CD62E+ endothelial microparticle (CD62E+EMP), high-sensitivity C-reactive protein (hs-CRP), aldosterone (ALD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), soluble tumor necrosis factor receptor-1 (sTNFR-1) and soluble tumor necrosis factor receptor-2 (sTNFR-2) in elderly patients with recurrent VA and assessed impacts of pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress on recurrent VA in elderly patients after coronary stenting. RESULTS: The levels of CD31+EMP, CD62E+EMP, hs-CRP, ALD, MDA, TNF-α, sTNFR-1 and sTNFR-2 were increased in recurrent malignant ventricular arrhythmia, sustained ventricular tachycardia, multiple ventricular premature beat and left and right ventricular bundle branch block groups (P < 0.001) in elderly patients with coronary reocclusions after coronary stent implantation. Upregulation of pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress markers induced recurrent VA in elderly patients after coronary stenting. CONCLUSIONS: High levels of pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress markers were associated with recurrent VA in elderly patients after coronary stenting. Our results suggested that the pro-inflammatory microparticles, pro-inflammatory cytokines and oxidative stress may simultaneously induce and aggravate recurrent VA in elderly patients after coronary stenting.

13.
Microbiome ; 8(1): 162, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213511

RESUMO

The capability of gut microbiota in degrading foods and drugs administered orally can result in diversified efficacies and toxicity interpersonally and cause significant impact on human health. Production of atherogenic trimethylamine N-oxide (TMAO) from carnitine is a gut microbiota-directed pathway and varies widely among individuals. Here, we demonstrated a personalized TMAO formation and carnitine bioavailability from carnitine supplements by differentiating individual TMAO productivities with a recently developed oral carnitine challenge test (OCCT). By exploring gut microbiome in subjects characterized by TMAO producer phenotypes, we identified 39 operational taxonomy units that were highly correlated to TMAO productivity, including Emergencia timonensis, which has been recently discovered to convert γ-butyrobetaine to TMA in vitro. A microbiome-based random forest classifier was therefore constructed to predict the TMAO producer phenotype (AUROC = 0.81) which was then validated with an external cohort (AUROC = 0.80). A novel bacterium called Ihubacter massiliensis was also discovered to be a key microbe for TMA/TMAO production by using an OCCT-based humanized gnotobiotic mice model. Simply combining the presence of E. timonensis and I. massiliensis could account for 43% of high TMAO producers with 97% specificity. Collectively, this human gut microbiota phenotype-directed approach offers potential for developing precision medicine and provides insights into translational research. Video Abstract.

14.
J Clin Sleep Med ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226331

RESUMO

STUDY OBJECTIVES: The association between schizophrenia and narcolepsy has been controversial. We conducted a prospective case control study of schizophrenia and comorbid narcolepsy type 1 in adolescents, compared to patients with either diagnosis alone and healthy controls using 18-F-fluorodeoxy glucose (FDG) positron emission tomography (PET), sleep studies, and neurocognitive tests. METHODS: We included eleven 9-20 years old patients with schizophrenia and comorbid narcolepsy type 1, 11 with narcolepsy type 1, 11 with schizophrenia, and 11 controls. All groups were matched for age and gender. Participants were required to submit to clinical interviews for sleep and psychiatric disorders, sleep questionnaires, continuous performance test (CPT), Wisconsin card sorting test (WCST), sleep studies including polysomnography (PSG), multiple sleep latency test (MSLT) and actigraphy, and PET studies. All data were analyzed to compare the differences between the four groups. RESULTS: The PET results demonstrated significant differences in the dual diagnoses group, compared with the three other groups. Compared to the controls, the dual diagnoses group had a significant presence of hypometabolism in the right mid frontal, right orbital inferior frontal, and right posterior cingulum and a significant presence of hypermetabolism in the left amygdala, bilateral striatum, bilateral substantia nigra, bilateral basal ganglia, and bilateral thalamus. CPT and WCST tests showed that the dual diagnoses group had the worst performance. CONCLUSIONS: Patients with schizophrenia and comorbid narcolepsy type 1 had different PET findings than those with either schizophrenia or narcolepsy type 1 alone. They also had more neurocognitive impairments and required additional interventions.

15.
Macromol Biosci ; : e2000301, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33205616

RESUMO

Poly(glycerol-sebacate) (PGS) is a biodegradable elastomer known for its mechanical properties and biocompatibility for soft tissue engineering. However, harsh thermal crosslinking conditions are needed to make PGS devices. To facilitate the thermal crosslinking, citric acid is explored as a crosslinker to form poly(glycerol sebacate citrate) (PGSC) elastomers. The effects of varying citrate contents and curing times are investigated on the mechanical properties, elasticity, degradation, and hydrophilicity. To examine the potential presence of unreacted citric acid, material acidity is monitored in relation to the citrate content and curing times. It is discovered that a low citrate content and a short curing time produce PGSC with tunable mechanical characteristics similar to PGS with enhanced elasticity. The materials demonstrate good cytocompatibility with human umbilical vein endothelial cells similar to the PGS control. The research study suggests that PGSC is a potential candidate for large-scale biomedical applications because of the quick thermal crosslink and tunable elastomeric properties.

16.
Mediators Inflamm ; 2020: 3432587, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132754

RESUMO

Sepsis remains a major global concern and is associated with high mortality and morbidity despite improvements in its management. Markers currently in use have shortcomings such as a lack of specificity and failures in the early detection of sepsis. In this study, we aimed to identify key genes involved in the molecular mechanisms of sepsis and search for potential new biomarkers and treatment targets for sepsis using bioinformatics analyses. Three datasets (GSE95233, GSE57065, and GSE28750) associated with sepsis were downloaded from the public functional genomics data repository Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using R packages (Affy and limma). Functional enrichment of the DEGs was analyzed with the DAVID database. Protein-protein interaction networks were derived using the STRING database and visualized using Cytoscape software. Potential biomarker genes were analyzed using receiver operating characteristic (ROC) curves in the R package (pROC). The three datasets included 156 whole blood RNA samples from 89 sepsis patients and 67 healthy controls. Between the two groups, 568 DEGs were identified, among which 315 were upregulated and 253 were downregulated in the septic group. These genes were enriched for pathways mainly involved in the innate immune response, T-cell biology, antigen presentation, and natural killer cell function. ROC analyses identified nine genes-LRG1, ELANE, TP53, LCK, TBX21, ZAP70, CD247, ITK, and FYN-as potential new biomarkers for sepsis. Real-time PCR confirmed that the expression of seven of these genes was in accordance with the microarray results. This study revealed imbalanced immune responses at the transcriptomic level during early sepsis and identified nine genes as potential biomarkers for sepsis.

17.
J Sci Food Agric ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33222240

RESUMO

BACKGROUND: The intestinal microbiota and metabolites play an important role in human health and immunity. However, few studies have investigated the long-term effects of stachyose on the human intestinal microbiota and metabolism. Therefore, in this study, the feces of infants were transplanted into germ-free mice, and the effect of long-term stachyose intake on intestinal metabolism was examined by comparing the results of microbiome and metabolome analyses. Ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) was used to study the effects of stachyose intake on the metabolites and metabolic pathways of the transplanted human intestinal microbiota. RESULTS: We observed that stachyose significantly altered the composition of the intestinal microbiota and metabolites, upregulated production of the metabolite taurocholic acid, downregulated amino acid metabolism, and significantly regulated the metabolism of taurine and hydroxytaurine, pantothenate and CoA biosynthesis, and other signaling pathways. CONCLUSION: These findings may provide a basis for elucidating the mechanism by which stachyose promotes host health. This article is protected by copyright. All rights reserved.

18.
Pediatr Hematol Oncol ; : 1-13, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231128

RESUMO

Development of chemo­resistance is ultimately responsible for treatment failure and relapse in B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism underlying glucocorticoid (GC) resistance remains unclear. This study was performed to identify GC resistance-related genes using the transcriptome chip from the GEO database, and preliminarily analyze drug resistance mechanism in B-ALL. Here, we found that ANXA5 expression was upregulated in B-ALL cells and high-level ANXA5 was associated with dexamethasone (DEX) resistance. Then, small interfering RNA (siRNA) was designed to silence ANXA5 expression in the B-ALL cell lines, and the apoptotic rate of cells treated with DEX was detected by flow cytometry. As a result, cell apoptosis was dramatically promoted in B-ALL cells following silencing of ANXA5 and DEX administration versus that in ANXA5-silenced alone or DEX-treated alone cells. It was further found that down-regulation of ANXA5 in B-ALL cells significantly increased the relative amount of cleaved Caspase 3 and Caspase 9 induced by DEX. Collectively, inhibition of ANXA5 gene expression may represent a novel method to restore the sensitivity of treatment-resistant B-ALL tumors to GC-induced cell death, which is of important clinical significance to overcome drug resistance associated with B-ALL.

19.
Phys Chem Chem Phys ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33231596

RESUMO

After a general introduction to the features and mechanisms of cytochrome c oxidases (CcOs) in mitochondria and aerobic bacteria, we present DFT calculated physical and spectroscopic properties for the catalytic reaction cycle compared with experimental observations in bacterial ba3 type CcO, also with comparisons/contrasts to aa3 type CcOs. The Dinuclear Complex (DNC) is the active catalytic reaction center, containing a heme a3 Fe center and a near lying Cu center (called CuB) where by successive reduction and protonation, molecular O2 is transformed to two H2O molecules, and protons are pumped from an inner region across the membrane to an outer region by transit through the CcO integral membrane protein. Structures, energies and vibrational frequencies for Fe-O and O-O modes are calculated by DFT over the catalytic cycle. The calculated DFT frequencies in the DNC of CcO are compared with measured frequencies from Resonance Raman spectroscopy to clarify the composition, geometry, and electronic structures of different intermediates through the reaction cycle, and to trace reaction pathways. X-ray structures of the resting oxidized state are analyzed with reference to the known experimental reaction chemistry and using DFT calculated structures in fitting observed electron density maps. Our calculations lead to a new proposed reaction pathway for coupling the PR → F → OH (ferryl-oxo → ferric-hydroxo) pathway to proton pumping by a water shift mechanism. Through this arc of the catalytic cycle, major shifts in pKa's of the special tyrosine and a histidine near the upper water pool activate proton transfer. Additional mechanisms for proton pumping are explored, and the role of the CuB+ (cuprous state) in controlling access to the dinuclear reaction site is proposed.

20.
J Cell Mol Med ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33164313

RESUMO

Endogenous electric field is considered to play an important role in promoting collective migration of epidermis to the wound centre. However, most studies are focused on the effect of bioelectric field on the movement and migration of single epithelial cell; the molecular mechanisms about collective migration of epidermal monolayers remain unclear. Here, we found that EFs dramatically promoted the collective migration of HaCaT cells towards the anode, activated the sheddase activity of ADAM17 and increased the phosphorylation level of EGFR. Moreover, EGFR phosphorylation and HB-EGF shedding level were significantly decreased by the ADAM17 inhibitor TAPI-2 or siADAM17 under EFs, which subsequently attenuated the directed migration of HaCaT sheets. Notably, the inhibition of EF-regulated collective migration by siADAM17 was rescued by addition of recombinant HB-EGF. Furthermore, we observed that F-actin was dynamically polarized along the leading edge of the migrated sheets under EFs and that this polarization was regulated by ADAM17/HB-EGF/EGFR signalling. In conclusion, our study indicated that ADAM17 contributed to the collective directional movement of the epidermal monolayer by driving HB-EGF release and activating EGFR under EFs, and this pathway also mediated the polarization of F-actin in migrating sheets, which is essential in directional migration.

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