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1.
Anal Biochem ; 597: 113669, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32126209

RESUMO

Lambda-cyhalothrin is a pyrethroid widely used in crop, fruit and vegetable production, but has potential health threats to human. Immunoassay is a cheap, rapid and facile method to detect lambda-cyhalothrin, yet wide application of this method still requires improvement in the construction of antigen. In this study, we developed a one-step lambda-cyhalothrin hapten synthesis that transformed the cyanide group in lambda-cyhalothrin to amide. Complete antigen was assembled by coupling the amide with succinic-anhydride-activated carrier proteins, and corresponding polyclonal antibodies were generated using Balb/c mice. Using antibody generated by the method in this paper, the competitive ELISA demonstrated the lowest detection limit of 3.772 µg/L for lambda-cyhalothrin, and no significant cross-reactivity for other pyrethroid pesticides was observed. All the results suggested we have established a more efficient technique of generating lambda-cyhalothrin antibody. Furthermore, since the activated proteins used in this study are highly controllable, we believe these proteins could potentially be the prototype of a series of standardized carrier proteins for the synthesis of complete antigens.

2.
J Cell Biochem ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32162364

RESUMO

The Iroquois homeobox gene 5 (IRX5), one of the members of the Iroquois homeobox family, has been identified to correlate with worse prognosis in many cancers, including colorectal cancer (CRC). In this study, upregulation of IRX5 revealed a great reduction in the proliferation of CRC colorectal cancer cell line SW480 and DLD-1, which was accompanied by G1/S arrest, increased expression in cyclin E1, P21, and P53 and a decrease in cyclin A2, B1, and D1. Furthermore, IRX5-mediated an increase expression of RH2A protein, the biomarker of DNA damage. Consequently, the SA-ß-gal level is higher in IRX5-overexpression cells compared to control ones, which showed elevated DNA damage triggered cellular senescence. Recapitulating the above findings, IRX5 exhibited higher levels of genomic instability. IRX5 may be a perspective target for cancer therapy and it deserves further investigation.

3.
Eur J Med Chem ; 193: 112194, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32203786

RESUMO

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death around the world. The current treatments of CRC exhibited high occurrence rate of side effects. Docetaxel (DTX), an important drug widely used in cancer chemotherapy, showed serious toxicity in CRC. Reducing toxicity of DTX could be a feasible and promising way to achieve the new indication of DTX for CRC. In this study, a series of MMP-7 activated octapeptide-DTX/4FDT prodrugs (6a-10a and 6b-10b) were designed and synthesized based on the features of MMP-7 which is highly expressed in CRC and could specially recognize octapeptides with specific sequences. Among them, 9a and 9b, both possessing an octapeptide Gly-Pro-Gln-Gly-Ile-Ala-Met-Gln moiety, were the most potent prodrugs. Compounds 9a and 9b were also tested their release rate in HCT116 cell culture fluids and tumor homogenate along with in vivo anti-CRC activity and systemic toxicity. Since 9a showed better anti-CRC activity and lower systemic toxicity than 9b in CRC tumor bearing mice, it was further evaluated for its acute toxicity, pharmacokinetics and tissue distribution in comparison with its parent drug DTX. These results revealed that 9a possessed good systemic stability, rapid release rate in CRC and reduced systemic toxicity, while retaining similar anti-CRC activity to its parent drug DTX. Thus, 9a, an MMP-7 polypeptide prodrug of DTX, has been identified as a promising candidate for the treatment of CRC.

4.
Molecules ; 25(5)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143323

RESUMO

An efficient approach to obtain functionalized rhodanines was developed through a base-assisted one-pot coupling and continuous cyclization of a primary amine, carbon disulfide, and methyl (2-chloroacetyl)carbamate. This conversion tolerates a broad range of functional groups and can be used to scale the preparation of N-substituted rhodanines in excellent yields.

5.
Mol Imaging Biol ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125599

RESUMO

PURPOSE: The aim of this study was to perform radiotheranostics with radioiodinated monoclonal antibodies (mAbs) for targeting cancer stem cells (CSCs) in human colorectal cancer xenografts and evaluate the relative advantage of a cocktail containing both [131I]CD133 mAb and [131I]CD44 mAb. PROCEDURES: Tumor-bearing mice were randomly divided into eight groups: [131I]CD133mAb, [131I]CD44 mAb, [131I]IgG isotype control, radioiodinated mAb cocktail, CD133 mAb, CD44 mAb, unradioiodinated mAb cocktail, and saline groups. In vivo single photon emission computed tomography (SPECT) imaging was used to monitor dynamically changes in the CSC population after treatment. The radioactivity uptake of tumors was quantified ex vivo. The expression of CD133 and CD44 after treatment was also assessed by immunohistochemistry and western blot. Tumor growth curves and survival curves were generated to assess treatment efficacy. Cell apoptosis and proliferation in xenografts 30 days after treatment were measured by TdT-mediated dUTP-biotin nick end labeling (aka, TUNEL) and Ki67 staining. The expression levels of biomarkers in xenografts 30 days after treatment were measured by flow cytometry. RESULTS: The radioimmunoimaging (RII) with in vivo SPECT showed that the CSC-targeting radioimmunotherapy (RIT) groups ([131I]CD133 mAb, [131I]CD44 mAb, and radioiodinated mAb cocktail groups) had intense accumulations of radiolabeled agents in the tumor areas. The ex vivo biodistribution confirmed these findings. In the CSC-targeting RIT groups, immunohistochemistry and western blot indicated significant reduction of specific target expression in the xenografts. The tumor growth curves and survival curves showed that the CSC-targeting RIT significantly inhibited tumor growth and prolonged mean survival, respectively. Significantly increased apoptosis and decreased proliferation in xenografts further confirmed the therapeutic efficacy of CSC-targeting RIT. Flow cytometry showed that the decreases in CSCs correlated with the presence of the corresponding antibodies. CONCLUSIONS: Our results suggest that the CSC-targeting RIT can effectively reduce CSCs which consequently inhibits tumor development. The radioiodinated mAb cocktail may generate enhanced CSC-targeting specificity.

6.
Food Funct ; 11(2): 1334-1348, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32043503

RESUMO

Huntington's disease (HD) is a genetic neurodegenerative disorder caused by a highly polymorphic CAG trinucleotide repeat expansion encoding an extended polyglutamine (polyQ) tract at the N-terminus of huntingtin protein (HTT). The polyQ tract promotes the formation of toxic oligomers and aggregates of HTT, which leads to neuronal dysfunction and death. Therapies to lower mutant HTT (mHTT) and its aggregates appear to be the most promising strategies. Ellagic acid (EA) has been marketed as a dietary supplement with various claimed benefits and neuroprotective effects on several neurodegenerative disorders, while its effect on mHTT pathology is still unknown. Here we reported that EA significantly attenuated motor and cognitive deficits in R6/2 mice. Moreover, EA significantly lowered mHTT levels, reduced neuroinflammation, rescued synapse loss, and decreased oxidative stress in R6/2 mouse brains. These findings indicated that EA has promising therapeutic potential for HD treatment.

7.
Bioorg Med Chem ; 28(7): 115356, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32067892

RESUMO

Past few years have seen an active pursuit of the inhibitors for the deacylation catalyzed by the seven human sirtuins (i.e. SIRT1-7) as valuable chemical biological/pharmacological probes of this enzymatic deacylation and lead compounds for developing novel therapeutics for human diseases. In the current study, we prepared eight monocyclic and one bicyclic analogs of a linear pentapeptide-based potent (sub-µM IC50's) pan-SIRT1/2/3 inhibitor Zheng laboratory discovered recently that harbors the catalytic mechanism-based SIRT1/2/3 inhibitory warhead Nε-thioacetyl-lysine at its central position. We found that the bicyclic analog exhibited largely comparable SIRT1/2/3 inhibitory potencies to those of the parent linear pentapeptide, however, the former is proteolytically much more stable than the latter. Moreover, the bicyclic analog displayed very weak inhibition against SIRT5/6/7, was cell permeable, and exhibited an anti-proliferative effect on the human SK-MEL-2 melanoma cells. This bicyclic analog could be a lead for the future development of more potent and still selective pan-SIRT1/2/3 inhibitors whose use in studies on human sirtuin biology, pharmacology, and medicinal chemistry could complement with the use of the potent inhibitors selective for a single human sirtuin.

8.
Nanoscale ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065185

RESUMO

We propose a strategy to construct dynamically tunable random lasers by continuously adjusting the excited state of gain molecules spatially confined in the nanoporous channels of metal-organic framework particles. Wavelength-tunable random lasers are achieved by thermally manipulating the intramolecular charge transfer process of gain molecules. The wavelength-tunable response to thermal stimuli exhibits excellent reversible behavior. We envisage that such random lasers based on metal-organic frameworks will raise new fundamental issues regarding light-matter interactions in complex photonic media and open up a new avenue toward highly efficient light-emitting devices.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32048201

RESUMO

Messenger RNA (mRNA) vaccines have attracted great interest in recent years due to their high potency, safety profile, and potential of rapid development. Although a number of mRNA vaccines have entered clinical trials, there remain several challenges. Inefficient in vivo delivery of mRNA is the foremost one. Here we synthesized a conjugate composed of ß-cyclodextrin (ß-CD) and branched polyethyleneimine (molecular weight 2 kDa, bPEI2k) to deliver an mRNA vaccine. The CD-PEI (CP) conjugate helped the encapsulated mRNA molecules pass through the plasma membranes and escape from the endosomes, which consequently ensured high transfection efficiency. On this basis, we optimized several structural elements of mRNA molecules via synthesizing an advanced cap structure and incorporating untranslated regions (UTRs) and an extended poly(A) tail into the sequence. These modifications led to a higher expression level of encoded proteins, which was expected to induce potent immune responses with a relatively low dosage. We also investigated the relevance of the administration route to the immune responses induced by CP-assisted mRNA vaccines with in vivo evidence, providing a basis for the selection of optimum administration route in specific cases. This CP-based mRNA vaccine platform, with an optimized mRNA structure and administrated in a most appropriate route, holds a promise to be applied to specific antigens in the future. Graphical abstract.

10.
J Colloid Interface Sci ; 565: 177-185, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31958657

RESUMO

Non-noble-metal-based catalysts for catalyzing the oxidative coupling of aldehydes and ammonia represent an efficient atom-economical synthetic route to produce nitriles. In this study, an effective Fe-modified N-doped carbon catalyst anchored on fibrous silica nanospheres (Fe-N/KCC-1-T) was successfully prepared by a facile strategy. 1,10-Phenanthroline with a strong chelating ability ensured the homogeneous, ultrafine distribution of Fe-based active sites, and the KCC-1 support material effectively enhanced the accessibility to these active sites, which corresponded to center-radial pore channels and a high surface area. As-fabricated Fe-N/KCC-1-T exhibited excellent catalytic performance for the ammoxidation of aldehydes under mild reaction conditions. A series of functionalized aldehydes were efficiently oxidized into the corresponding nitriles by using air as the green oxidant. Moreover, the catalyst was recycled for at least five runs without any clear decrease in the performance. Hence, this study is expected to provide an eco-friendly synthetic route to produce nitriles from easily available aldehydes and ammonia by using a cost-effective catalyst.

11.
Nanoscale ; 12(5): 3359-3369, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31984408

RESUMO

The tumor microenvironment (TME) acts as an ecosystem that includes not only tumor cells, but also stromal cells such as cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). In addition, the abnormal extracellular environment (ECM), of which the mechanical forces are regulated by fibronectin (Fn) and collagen I, orchestrates tumorigenesis and progression by directly promoting invasion and cellular transformation of the ecosystem. Herein, we develop a novel peptide-modified liposome incorporated into doxorubicin (FnBPA5-AAN-Dox) as an ecological therapy system, which targets not only the cellular compartment but also non-cellular components of breast cancer. FnBPA5 is a Fn-binding peptide showing high affinity with relaxed Fn and collagen I in the ECM as well as α-SMA-expressing CAFs. However, the fast clearance by Fn-excreting organs such as the liver and spleen limits the accumulation of FnBPA5-Dox in the TME. The AAN peptide, which targets legumain overexpressed in the TAMs, could extend the circulation time and improve the therapeutic response as well as modulate the tumor immune microenvironment (TMIE). Given twice at an equivalent dose of 5 mg kg-1 intravenously, the multi-in-one 'ecological therapy' applied AAN-FnBPA5-Dox showed excellent antitumor efficacy in 4T1 breast cancer mice, and the tumor growth inhibition (TGI) is up to 98.20% compared with saline. Immunofluorescence, flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) results revealed that the dramatic improvement in antitumor efficacy can be attributed to the multifunctional targets of the drug delivery system.

12.
Chem Commun (Camb) ; 56(12): 1875-1878, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31950940

RESUMO

Photodetectors play a key role in the military, aerospace, communications, bio-imaging, etc. In this study, we fabricate photodetector devices based on (CH3NH3)2FeCuI4Cl2 (MA2FeCuI4Cl2) and (CH3NH3)2InCuI6 (MA2InCuI6) for the first time. We find that the device based on MA2InCuI6 is highly selective for ultraviolet light (880 nA mW-1) and shows high anti-interference for visible-light (20-50 nA mW-1). The electrochemical impedance results indicate that the value (480 ± 10 Ω) of the resistance based on the MA2InCuI6 photodetector device is much smaller than that (1 ± 0.001 MΩ) based on the MA2FeCuI4Cl2 photodetector device, which in turn proves the difference in photoelectric response.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31927906

RESUMO

Metal-nanocluster-doped porous materials are attracting considerable research attention due to their specific catalytic performance. In this study, core-shell metal-organic frameworks@covalent organic polymer (MOF@COP) nanocomposites were formed by the covalent linking of chemically stable COP on the surface of size-selective UiO-66-NH2. Pd nanoclusters with an average diameter of ∼0.8 nm were successfully confined in UiO-66-NH2@COP, and the obtained nanoreactor, referred to as UiO-66-NH2@COP@Pd, exhibited abundant porosity, high stability, and large surface area. Notably, the UiO-66-NH2@COP@Pd nanoreactor exhibited superior catalytic activity and stability for the catalytic reduction of 4-nitrophenol and hydrogenation of other nitroarenes, demonstrating the potential of Pd-cluster-doped MOF@COP hybrid materials as candidates for efficient catalytic hydrogenation. This study may provide new avenues for the construction of MOF@COP-hybrid-material-based heterogeneous catalysts for efficient catalytic applications.

14.
J Control Release ; 320: 457-468, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31972242

RESUMO

Glomerulonephritis related renal failure is a frequent cause of end-stage renal disease, and immunoglobulin A nephropathy (IgAN) is the most frequent type of primary glomerulonephritis. As damage induced by IgAN mostly attributes to inflammation responses, inhibiting inflammation in glomerulus can protect normal renal function and delay the onset of renal failure. Hence, reducing levels of p38 MAPK and p65 which are essential regulators in p38 MAPK and NF-κB related inflammation responses could be effective against IgAN. Here, we rationally designed and constructed size- and surface charge- dependent glomerulus-targeting liposomal nanoparticles which are loaded with both p38α MAPK and p65 siRNA. Experiments show that our nanoparticles successfully crossed fenestrated endothelium, accumulated in mesangial cells and endothelial cells, efficiently silenced p38α MAPK and p65 genes, and eventually alleviated proteinuria, inflammation and excessive extracellular matrix deposition in mouse IgAN models. This siRNA co-delivery system thus represents a promising treatment option for IgAN and offers a versatile platform for other glomerular problems. Our work also highlights a novel strategy of glomerulus-targeting and an encouraging therapeutic route for other inflammatory diseases.

15.
Int J Syst Evol Microbiol ; 70(1): 240-245, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31661055

RESUMO

A novel Gram-stain-negative, strictly aerobic, rod-shaped, non-motile and yellow-pigmented bacterial strain, designated T58T, was isolated from a marine sediment sample collected from the coastal area of Weihai, PR China. Strain T58T was most closely related to Hyunsoonleella pacifica SW033T with 97.1 % 16S rRNA gene sequence similarity, followed by Hyunsoonleella jejuensis KCTC 22242T (96.9 %). Based on 16S rRNA gene sequences, the phylogenetic analysis indicated that strain T58T represented a member of the genus Hyunsoonleella within the family Flavobacteriaceae of the phylum Bacteroidetes. Strain T58T was found to grow optimally at 30 °C, at pH 7.0-7.5 and in the presence of 2.0-3.0 % (w/v) NaCl. The major fatty acids were iso-C15  :  0, iso-C15 : 1 G, iso-C17 : 0 3-OH and iso-C15 : 0 3-OH. The major isoprenoid quinone was menaquinone 6 (MK-6). The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and two unidentified lipids. The DNA G+C content of the genomic DNA was 35.0 mol%. On the basis of its phylogenetic, phenotypic and chemotaxonomic characteristics, strain T58T is considered to represent a novel species of the genus Hyunsoonleella, for which the name Hyunsoonleella flava sp. nov. is proposed. The type strain is T58T (=KCTC 72081T=MCCC 1H00359T).


Assuntos
Flavobacteriaceae/classificação , Sedimentos Geológicos/microbiologia , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/isolamento & purificação , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
16.
Plant Cell Environ ; 43(2): 358-373, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31675439

RESUMO

The endophytic fungus Falciphora oryzae was initially isolated from wild rice (Oryza granulata) and colonizes many crop species and promotes plant growth. However, the molecular mechanisms underlying F. oryzae-mediated growth promotion are still unknown. We found that F. oryzae was able to colonize Arabidopsis thaliana. The most dramatic change after F. oryzae inoculation was observed in the root architecture, as evidenced by increased lateral root growth but reduced primary root length, similar to the effect of auxin, a significant plant growth hormone. The expression of genes responsible for auxin biosynthesis, transport, and signalling was regulated in Arabidopsis roots after F. oryzae cocultivation. Indole derivatives were detected at significantly higher levels in liquid media after cocultivation compared with separate cultivation of Arabidopsis and F. oryzae. Consistently, the expression of indole biosynthetic genes was highly upregulated in F. oryzae upon treatment with Arabidopsis exudates. Global analysis of Arabidopsis gene expression at the early stage after F. oryzae cocultivation suggested that signals were exchanged to initiate Arabidopsis-F. oryzae interactions. All these results suggest that signalling molecules from Arabidopsis roots are perceived by F. oryzae and induce the biosynthesis of indole derivatives in F. oryzae, consequently stimulating Arabidopsis lateral root growth.

17.
Biomater Sci ; 8(2): 530-543, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750453

RESUMO

Immunotherapy has become an increasingly important area in the medical field at present. As it is often difficult for synthetic carriers to overcome regulatory hurdles for clinical translation, bionic cell-derived carriers are attracting considerable interest due to their better biocompatibility and lower toxicity. Moreover, biomimetic cell-derived nanocarriers may achieve different specific biological effects due to the benefit from their host attributes. In this review, we introduce the technologies that are under extensive investigation, including extracellular vesicle-based formulation technology and cell membrane coating technology, summarize various applications that have been developed based on these technologies for modulating immune responses, and briefly discuss the future perspectives of this field. With a better understanding of these biomimetic technologies, in conjunction with the current advanced biotechnology methods, we expect that the continuing development of biomimetic cell-derived nanocarriers will promote their clinical applications.

18.
J Ethnopharmacol ; 247: 112283, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31605736

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bulbus Fritillaria cirrhosa D. Don (BFC) is a Chinese traditional herbal medicine that has long been used as an indispensable component in herbal prescriptions for bronchopulmonary diseases due to its well-established strong anti-inflammation and pulmonary harmonizing effects. Interestingly, there are few case reports in traditional Chinese medicine available where they found it to contribute in anti-tumor therapies. Imperialine is one of the most favored active substances extracted from BFC and has been widely recognized as an anti-inflammatory agent. AIM OF THE STUDY: The aim of the current work is to provide first-hand evidences both in vitro and in vivo showing that imperialine exerts anti-cancer effects against non-small cell lung cancer (NSCLC), and to explore the molecular mechanism of this anti-tumor activity. It is also necessary to examine its systemic toxicity, and to investigate how to develop strategies for feasible clinical translation of imperialine. MATERIALS AND METHODS: To investigate anti-NSCLC efficacy of imperialine using both in vitro and in vivo methods where A549 cell line were chosen as in vitro model NSCLC cells and A549 tumor-bearing mouse model was constructed for in vivo study. The detailed underlying anti-cancer mechanism has been systematically explored for the first time through a comprehensive set of molecular biology methods mainly including immunohistochemistry, western blot and enzyme-linked immunosorbent assays. The toxicity profile of imperialine treatments were evaluated using healthy nude mice by examining hemogram and histopathology. An imperialine-loaded liposomal drug delivery system was developed using thin film hydration method to evaluate target specific delivery. RESULTS: The results showed that imperialine could suppress both NSCLC tumor and associated inflammation through an inflammation-cancer feedback loop in which NF-κB activity was dramatically inhibited by imperialine. The NSCLC-targeting liposomal system was successfully developed for targeted drug delivery. The developed platform could favorably enhance imperialine cellular uptake and in vivo accumulation at tumor sites, thus improving overall anti-tumor effect. The toxicity assays revealed imperialine treatments did not significantly disturb blood cell counts in mice or exert any significant damage to the main organs. CONCLUSIONS: Imperialine exerts anti-cancer effects against NSCLC both in vitro and in vivo, and this previously unknown function is related to NF-κB centered inflammation-cancer feedback loop. Imperialine mediated anti-cancer activity is not through cytotoxicity and exhibit robust systemic safety. Furthermore, the liposome-based system we commenced would dramatically enhance therapeutic effects of imperialine while exhibiting extremely low side effects both on cellular and in NSCLC model. This work has identified imperialine as a promising novel anti-cancer compound and offered an efficient target-delivery solution that greatly facilitate practical use of imperialine.


Assuntos
Alcaloides/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cevanas/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Fritillaria/química , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Alcaloides/efeitos adversos , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Contagem de Células Sanguíneas , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Cevanas/efeitos adversos , Cevanas/química , Cevanas/isolamento & purificação , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Retroalimentação Fisiológica/efeitos dos fármacos , Humanos , Lipossomos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Testes de Toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Brain Res Bull ; 154: 9-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31626954

RESUMO

Hypertension is a common complication of metabolic abnormalities associated with cardiovascular system and characterized by sexual dimorphism in mammals. Fibroblast growth factor-21 (FGF-21) plays a critical role in metabolic-disorder related hypertension through the afferent loop of baroreflex. However, the gender difference in FGF-21-mediated blood pressure (BP) regulation via sexual dimorphic expression of FGFRs in the nodose (NG) and nucleus tractus solitarius (NTS) were not elucidated in physiological and genomic form of hypertension. The gene and protein expression of FGFRs were tested by qRT-PCR, immunoblotting and immunostaining; the serum level of FGF21 was tested using ELISA; The BP was monitored while FGF21 was nodose microinjected. The results showed that more potent BP reduction was confirmed in female vs. male rats by nodose microinjection of rhFGF-21 along with higher expression of FGFR2 and FGFR4 in the nodose compared with age-match male and ovariectomized (OVX) rats, rather than other receptor subtypes, which is consistent well with immunohistochemical analysis. Additionally, serum FGF-21 was significantly higher in female-WKY, and this level of FGF-21 was dramatically declined in spontaneous hypertensive rats (SHR) with significant down-regulation of FGFR1/R4 for male-SHR and FGFR2/FGFR4 for female-SHR, respectively. Apparently, high BP of SHR of either sex could be reduced by rhFGF-21 nodose microinjection. These data extends our current understanding that sexual-specific distribution/expression of FGF-21/FGFRs is likely to contribute at least partially to sexual dimorphism of baroreflex afferent function on BP regulation in rats. FGF-21-mdiated BP reduction sheds new light on clinical management of primary/genomic form of hypertension.

20.
Materials (Basel) ; 12(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795224

RESUMO

With the increase of time, the shrinkage of materials at fixed temperature could enhance the failure of fasteners. We report a potential way to alter the volume/length of alloy automatically through isothermal aging due to pseudospinodal decomposition mechanism. The volume of Ti-10V-2Fe-3Al alloy first shrunk and then expanded during isothermal aging at 550 °C. It can fit tightly and make up for volume loss. Transmission electron microscopy observation exhibits no obvious coarsening of intragranular α phase with the increasing time. However, composition evolution with time shows a gradual change through energy dispersive spectrometer analysis. The result shows that ß stabilizers, V and Fe, are prone to diffuse to the ß matrix, while α stabilizers, Al, prefer to segregate to the α phase. First principle calculations suggest that the structure transition for ß to α cause the first decrease of volume, and the diffusion of V, Fe and Al is the origin of the later abnormal increase of volume.

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