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1.
Magn Reson Med ; 87(1): 249-262, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34427341

RESUMO

PURPOSE: To optimize pseudo-continuous arterial spin labeling (pCASL) for 7 T, and to further improve the labeling efficiency with parallel RF transmission transmit B1 ( B 1 + ) shimming. METHODS: pCASL parameters were optimized based on B 1 + / B 0 field distributions at 7 T with simulation. To increase labeling efficiency, the B 1 + amplitude at inflowing arteries was increased with parallel RF transmission B 1 + shimming. The "indv-shim" with shimming weights calculated for each individual subject, and the "univ-shim" with universal weights calculated on a group of 12 subjects, were compared with circular polarized (CP) shim. The optimized pCASL sequences with three B 1 + shimming modes (indv-shim, univ-shim, and CP-shim) were evaluated in 6 subjects who underwent two repeated scans 24 hours apart, along with a pulsed ASL sequence. Quantitative metrics including mean B 1 + amplitude, perfusion, and intraclass correlation coefficient were calculated. The optimized 7T pCASL was compared with standard 3T pCASL on 5 subjects, using spatial SNR and temporal SNR. RESULTS: The optimal pCASL parameter set (RF duration/gap = 300/250 us, G ave = 0.6 mT / m , g R a t i o = 10 ) achieved robust perfusion measurement in the presence of B 1 + / B 0 inhomogeneities. Both indv-shim and univ-shim significantly increased B 1 + amplitude compared with CP-shim in simulation and in vivo experiment (P < .01). Compared with CP-shim, perfusion signal was increased by 9.5% with indv-shim (P < .05) and by 5.3% with univ-shim (P = .35). All three pCASL sequences achieved fair to good repeatability (intraclass correlation coefficient ≥ 0.5). Compared with 3T pCASL, the optimized 7T pCASL achieved 78.3% higher spatial SNR and 200% higher temporal SNR. CONCLUSION: The optimized pCASL achieved robust perfusion imaging at 7 T, while both indv-shim and univ-shim further increased labeling efficiency.

2.
Anal Biochem ; 637: 114474, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34801482

RESUMO

Yaobitong capsule (YBTC) has been used for the prevention and treatment of inflammation-related lumbago and leg pain. However, its intervention mechanism still remains unclear. This study was aimed to evaluate the control efficiency of YBTC on adjuvant-induced rheumatoid arthritis (RA) rats by metabonomic method and to explore its possible anti-arthritis mechanism. Taking into account the complexity of endogenous metabolites in serum samples, an integrated metabolomics method based on RP/HILIC-UHPLC-Q-TOF MS was developed, to overcome the limitations of a single chromatographic in this study. The results showed that 32 potential biomarkers of arthritis were identified, primarily related to amino acid metabolism, glucose metabolism, lipid metabolism and nucleotide metabolism. Further receiver operating characteristic analysis revealed that the area under the curve of two down-regulated metabolites (3-Hydroxy-hexadecanoic acid, 2-Oxoarginine) and one up-regulated metabolite (l-Glutamic acid) among 32 biomarkers were 0.906, 0.969 and 1.000, respectively, indicating that high predictive ability of this method for RA. In this study, an integrated serum metabolomics method based on high-resolution mass spectrometry was successfully established for the first time to study the intervention mechanism of YBTC in RA, providing evidence regarding the clinical application of YBTC and a new insight for the prevention of RA in the future.

3.
J Phys Chem Lett ; : 11645-11651, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822249

RESUMO

Solution-processed quasi-two-dimensional (quasi-2D) perovskites with self-assembled multiple quantum well (QW) structures exhibit enhanced exciton binding energy, which is ideal for use as light emitters. Here, we have found that postannealing is important to promoting the QWs' composition transfer, and we explored the correlation among the annealing time, the external quantum efficiency (EQE), and the operational stability of the device. During thermal annealing, the low-n QWs will gradually convert to high-n phases, accompanied by an increase in grain size. The EQE and working stability of the device exhibit different annealing-time dependences; that is, with the extension of the annealing time, the EQE gradually decreases while the working stability improves. By introducing trimethylolpropane trimethacrylate (TPTA) to passivate the emitting-region defects, the annealing-time dependence of the EQE was effectively eliminated due to the reduction of the nonradiative recombination rate, wherefore high efficiency and stability can be achieved simultaneously. Our research provides an effective way to develop highly efficiency and stable perovskite light-emitting diodes.

4.
Ecotoxicol Environ Saf ; 228: 112988, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808505

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous pollutant that results in hepatotoxicity. However, an understanding of the systematic mechanism of hepatic injury caused by DEHP remains limited. Here, we performed a comprehensive metabolomics and transcriptomics analyses to describe hepatic responses of rats to long-term DEHP exposure and, together with pathology and functional injury of liver, systematically analyzed the pathogenesis and mechanisms of liver damage. SD rats were exposed to 0 and 600 mg/kg/day DEHP for 12 weeks. Thereafter, biochemical indicators and histopathological changes regarding liver function were detected. Metabolomics and transcriptomics profiles of rat liver samples were analyzed using a UPLC-MS/MS system and Illumina Hiseq 4000, respectively. DEHP induced hepatocyte structural alterations and edema, depressed monooxygenase activity, decreased antioxidant activities, aggravated oxidative damage, blocked the tricarboxylic acid cycle and respiratory chain, and disturbed glucose homeostasis in the liver. These findings indicate that reactive oxygen species play a major role in these events. Overall, this study systematically depicts the comprehensive mechanisms of long-term DEHP exposure to liver injury and highlights the power of metabolomics and transcriptomics platforms in the mechanistic understanding of xenobiotic hepatotoxicity.

5.
Adv Mater ; : e2105133, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676914

RESUMO

The zinc (Zn)-ion battery has attracted much attention due to its high safety and environmental protection. At present, the critical issues of the generation of dendrites and the accumulation of dead Zn on the surface will lead to a sharp decline of the battery life. Zn dendrites can be inhibited to some extent by constructing an interface protective coating. However, the existing rigid coating method cannot maintain conformal contact with Zn due to the volume change of Zn deposition and will cause fracture irreversibly during the cycle. Here, a highly self-adaptable poly(dimethylsiloxane) (PDMS)/TiO2- x coating is developed that can dynamically adapt to volume changes and inhibit dendrites growth. PDMS has high dynamic and self-adaptability due to the crosslinking of the B-O bond. In addition, the rapid and uniform transfer of Zn2+ is induced by the oxygen-vacancy-rich TiO2- x . The assembled cells still achieve 99.6% coulombic efficiency after 700 cycles at a current density of 10 mA cm-2 . The adaptive interface coating constructed provides a sufficient guarantee for the stable operation of the Zn anode.

6.
Comput Intell Neurosci ; 2021: 2993870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603429

RESUMO

Today, the global exchange market has been the world's largest trading market, whose volume could reach nearly 5.345 trillion US dollars, attracting a large number of investors. Based on the perspective of investors and investment institutions, this paper combines theory with practice and creatively puts forward an innovative model of double objective optimization measurement of exchange forecast analysis portfolio. To be more specific, this paper proposes two algorithms to predict the volatility of exchange, which are deep learning and NSGA-II-based dual-objective measurement optimization algorithms for the exchange investment portfolio. Compared with typical traditional exchange rate prediction algorithms, the deep learning model has more accurate results and the NSGA-II-based model further optimizes the selection of investment portfolios and finally gives investors a more reasonable investment portfolio plan. In summary, the proposal of this article can effectively help investors make better investments and decision-making in the exchange market.


Assuntos
Aprendizado Profundo , Algoritmos , Investimentos em Saúde
7.
EMBO Rep ; : e52702, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34693625

RESUMO

TNF stimulation generates pro-survival signals through activation of NF-κB that restrict the build-in death signaling triggered by TNF. The competition between TNF-induced survival and death signals ultimately determines the fate of a cell. Here, we report the identification of Bclaf1 as a novel component of the anti-apoptotic program of TNF. Bclaf1 depletion in multiple cells sensitizes cells to TNF-induced apoptosis but not to necroptosis. Bclaf1 exerts its anti-apoptotic function by promoting the transcription of CFLAR, a caspase 8 antagonist, downstream of NF-κB activation. Bclaf1 binds to the p50 subunit of NF-κB, which is required for Bclaf1 to stimulate CFLAR transcription. Finally, in Bclaf1 siRNA administered mice, TNF-induced small intestine injury is much more severe than in control mice with aggravated signs of apoptosis and pyroptosis. These results suggest Bclaf1 is a key regulator in TNF-induced apoptosis, both in vitro and in vivo.

8.
Nanoscale ; 13(29): 12697-12710, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477620

RESUMO

A small size effect could be conducive to enhancing the electrochemical performance, while the mechanism by which they also increase the capacitance for carbon electrode materials has not been established. Here, ultrasmall polyacrylonitrile particles with controllable sizes are supported on poly(ionic liquid)s microspheres (PILMs/PAN) by epitaxial polymerization growth strategy. Unlike traditional subtraction formulas in developing a porous architecture, we report on the synthesis of creating numerous micro/mesopores in carbon materials by addition theorem, and thus making for the perfection of packing density, which has not been reported yet. As an example, PILMC/PAN-L with a well-balanced specific surface area of 875.38 m2 g-1 and packing density of 1.05 g cm-3 demonstrated gravimetric and volumetric capacitances of 309 F g-1 and 324.45 F cm-3 at 0.5 A g-1, showing good rate performance and stable cyclability. Moreover, the underlying mechanism is thoroughly developed using multiple electrochemical methods. On this basis, this work would afford avenues to further enhancing the electrochemical performance, especially in exploring advanced carbon materials.

9.
Expert Rev Clin Pharmacol ; 14(10): 1295-1303, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34488513

RESUMO

BACKGROUND: This study aimed to quantitatively evaluate factors influencing the efficacy and safety of the docetaxel-platinum regimen to provide reliable information for optimizing chemotherapy regimens. RESEARCH DESIGN AND METHODS: A parametric survival function model was used to describe the time course of overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) receiving a docetaxel-platinum regimen. A random-effects model in a single-arm meta-analysis was used to analyze the objective response rate and grade 3-4 adverse event rates based on various docetaxel-platinum regimens. RESULTS: The model revealed that the risk of death in East Asians was approximately 1.5-fold higher than that in non-East Asians, with a median OS of 13.7 (95% confidence interval [CI]: 12.8-14.7) months and 9.3 (95% CI: 7.7-11.1) months, respectively. No significant impact of different administration regimens on OS was found. However, when drug exposure increased, the incidence of grade 3-4 anemia or neutropenia significantly increased. CONCLUSIONS: The docetaxel-platinum regimen has different efficacies in the treatment of advanced NSCLC between East Asian and non-East Asian populations. A better benefit-risk ratio can be obtained with a lower exposure regimen of docetaxel combined with platinum.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel/administração & dosagem , Humanos , Neoplasias Pulmonares/patologia , Modelos Estatísticos , Compostos de Platina/administração & dosagem , Análise de Sobrevida , Taxa de Sobrevida
10.
Photoacoustics ; 24: 100302, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34540586

RESUMO

Multiple objective assessments have been used to assess the activity of keloids to compare different therapeutic regimens and facilitate the best individual treatment choice for patients, but none of them are standardized. A multimodal photoacoustic/ultrasonic (PA/US) imaging system, including photoacoustic imaging, elastography, ultra-micro-angiography, and conventional US technologies (gray scale US, color Doppler US, and power Doppler US), was applied to evaluate keloids by a radiologist. Growing stages were defined by patients, and Vancouver Scar Scale (VSS) was assessed by a plastic surgeon. A comprehensive model based on multimodal ultrasound parameters (poor-echo pattern, high vascular density, decreased elasticity, and low SO2 within the keloid) and VSS might be a potential indicator of active keloids, comparing with VSS alone. The multimodal PA/US imaging system could be a promising technique for keloids assessment.

11.
J Exp Clin Cancer Res ; 40(1): 273, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452627

RESUMO

BACKGROUND: Expression of aberrant cyclin G2 is a key factor contributing to cancer biological processes, including glioma. However, the potential underlying mechanisms of cyclin G2 in the glioma tumor immune microenvironment remain unclear. METHODS: Co-immunoprecipitation (co-IP), in situ proximity ligation assay (PLA), and in vitro kinase assay were conducted to reveal the underlying mechanism by which cyclin G2 regulates Y10 phosphorylation of LDHA. Further, the biological roles of cyclin G2 in cell proliferation, migration, invasion capacity, apoptosis, glycolysis, and immunomodulation were assessed through in vitro and in vivo functional experiments. Expressions of cyclin G2 and Foxp3 in glioma specimens was determined by immunohistochemistry. RESULTS: In this study, we found that cyclin G2 impeded the interaction between LDHA and FGFR1, thereby decreasing Y10 phosphorylation of LDHA through FGFR1 catalysis. Cyclin G2 inhibited proliferation, migration, invasion capacity, and glycolysis and promoted apoptosis glioma cells via suppressing Y10 phosphorylation of LDHA. Moreover, we further verified that cyclin G2 reversed the immunosuppressive to antitumor immune microenvironment through inhibiting lactate production by glioma cells. Besides, cyclin G2 potentiated PD-1 blockade and exerted strong antitumor immunity in the glioma-bearing mice model. CONCLUSIONS: Cyclin G2 acts as a potent tumor suppressor in glioma and enhances responses to immunotherapy. Our findings may be helpful in selecting glioma patients for immunotherapy trials in the future.

12.
Cancer Sci ; 112(11): 4722-4735, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34431598

RESUMO

The Wnt/ß-catenin signaling pathway plays an important role in tissue homeostasis, and its malignant activation is closely related to the occurrence and development of many cancers, especially colorectal cancer with adenomatous polyposis coli (APC) and CTNNB1 mutations. By applying a TCF/lymphoid-enhancing factor (LEF) luciferase reporter system, the high-throughput screening of 18 840 small-molecule compounds was performed. A novel scaffold compound, C644-0303, was identified as a Wnt/ß-catenin signaling inhibitor and exhibited antitumor efficacy. It inhibited both constitutive and ligand activated Wnt signals and its downstream gene expression. Functional studies showed that C644-0303 causes cell cycle arrest, induces apoptosis, and inhibits cancer cell migration. Moreover, transcription factor array indicated that C644-0303 could suppress various tumor-promoting transcription factor activities in addition to Wnt/ß-catenin. Finally, C644-0303 suppressed tumor spheroidization in a 3-dimensional cell culture model and inhibited xenograft tumor growth in mice. In conclusion, we report a novel structural small molecular inhibitor targeting the Wnt/ß-catenin signaling pathway that has therapeutic potential for colorectal cancer treatment.


Assuntos
Polipose Adenomatosa do Colo/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Descoberta de Drogas , Feminino , Células HCT116 , Células HT29 , Humanos , Luciferases , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular/métodos , Esferoides Celulares/efeitos dos fármacos , Fatores de Transcrição TCF , Fatores de Transcrição/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética
13.
J Cell Mol Med ; 25(18): 8973-8984, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34409723

RESUMO

NF-κB, a critical cytokine of inflammatory bowel diseases (IBD), is a viable marker to reflect the inflammatory activity of the intestine. We aimed to develop NF-κB-targeted microbubbles (MBs) and perform molecular contrast-enhanced ultrasound (CEUS) to quantify NF-κB expressions on the intestinal wall in IBD mice in vivo. In this study, NF-κB-targeted MBs were fabricated by connecting biotin-loaded NF-κB antibodies and avidin-loaded MBs. NF-κB-targeted MBs presented as transparent and round bubbles with an average diameter of 1.03/µm±0.01. The specific binding of targeted MBs and inflammatory cells was validated by in vitro experiments, including flow cytometry, Western blot and immunofluorescence, which revealed the specific binding of targeted MBs and inflammatory cells. Subsequently, NF-κB-targeted CEUS imaging was performed on mice with chemical-induced colitis, and the peak intensity (PI) and time-to-peak (TTP) were quantified. Pathological and immunohistochemical (IHC) examinations were further implemented. For the target CEUS group, fast enhancement followed by slow subsiding was observed. The PI of target CEUS of the IBD mice was significantly higher than that of non-target CEUS of the IBD mice, healthy controls and target CEUS of the treated IBD mice (34835%[13379-73492%] VS 437%[236-901%], 130%[79-231%], 528%[274-779%], p<0.0001), in accordance with the IHC results of NF-κB expressions. The TTP of target CEUS of the treated mice was significantly higher than that of untreated mice (35.7s [18.1-49.5s] VS 8.3s [4.2-12.5s], p<0.0001). Therefore, we suggested that NF-κB-targeted CEUS could accurately detect and quantify NF-κB expressions on the intestinal walls of IBD, enabling the evaluation of intestinal inflammation.

14.
Micromachines (Basel) ; 12(7)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34198959

RESUMO

In this paper, an investigation of cutting strategy is presented for the optimization of machining parameters in the ultra-precision machining of polar microstructures, which are used for optical precision measurement. The critical machining parameters affecting the surface generation and surface quality in the machining of polar microstructures are studied. Hence, the critical ranges of machining parameters have been determined through a series of cutting simulations, as well as cutting experiments. First of all, the influence of field of view (FOV) is investigated. After that, theoretical modeling of polar microstructures is built to generate the simulated surface topography of polar microstructures. A feature point detection algorithm is built for image processing of polar microstructures. Hence, an experimental investigation of the influence of cutting tool geometry, depth of cut, and groove spacing of polar microstructures was conducted. There are transition points from which the patterns of surface generation of polar microstructures vary with the machining parameters. The optimization of machining parameters and determination of the optimized cutting strategy are undertaken in the ultra-precision machining of polar microstructures.

15.
Langmuir ; 37(27): 8323-8330, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34210124

RESUMO

Three-dimensional metallic nanonetworks (3D-MNWs) demonstrate unique performances across a wide range of fields, and their facile and green synthetic method is of high significance. Herein, we report a self-generated-nanobubble scaffolding strategy for the fabrication of 3D-MNWs, which employs aqua ammonia (AA) as a nanobubble reservoir and avoids the use of any surfactants or polymeric capping agents. Benefiting from the interaction between ammonia and metallic nanoparticles, finely interlocked nanonetworks (Au, Pt, Ag, and Cu) with curved geometry and abundant pores are obtained by precisely controlling the anisotropic kinetic growth using a strong reducing agent and a high concentration of AA. As a demonstration, the methanol oxidation reaction (MOR) is tested to assess the electrocatalytic performance of the Pt 3D-MNWs. The peak current of Pt 3D-MNWs reaches 152 mA/mgPt, which is 2.5 times higher than that of commercial Pt black. This unique nanobubble-assisted strategy has great potential in the basic synthetic prototype for polyporous nanomaterials.

16.
Int J Biol Sci ; 17(9): 2367-2379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239363

RESUMO

Recombinant human bone morphogenetic proteins (rhBMPs) can stimulate bone formation and growth in the treatment of spinal fusions and nonunions. However, it is still unclear whether rhBMPs function in the prevention of intervertebral disc degeneration (IDD). Here, we discovered that BMP levels were decreased in IDD patients, which impaired the BMP/Smad (Mothers against decapentaplegic homologs) signaling. Conducting a microarray assay in Smad4-knockdown cells, we found that expression of PUMA (p53-upregulated modulator of apoptosis) was significantly induced. The molecular analysis revealed that Smad4 recruited HDAC1 (histone deacetylase 1) and the phosphorylated Smad1/5/8 to dock on the promoter of PUMA to repress its expression. The impairment of BMP/Smad signaling in IDD patients caused the significant induction of Puma-dependent apoptosis and resulted in the pathogenesis of IDD. In vitro knockdown of BMP receptors (BMPR1a and BMPR2) in nucleus pulposus (NP) cells could mimic the molecular changes of BMP/Smad signaling and Puma-dependent apoptotic signaling that were observed in IDD patients. Exposing NP cells to RITA (reactivating p53 and inducing tumor apoptosis) small molecule and rhBMP2 (or rhBMP7), we observed that rhBMP2/7 could significantly decrease protein levels of Puma and its downstream proapoptotic molecules, blocking cell apoptosis. Importantly, administration of rhBMPs in aged rats could inhibit the occurrence of IDD. Our results provide a link between BMP/Smad signaling and Puma-dependent apoptotic signaling, revealing a new mechanism of how BMPs contribute to IDD pathogenesis and providing evidence that rhBMPs may decrease apoptosis and improve the outcome of IDD.

17.
Small ; 17(26): e2007543, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34096175

RESUMO

Halide perovskites are promising photoactive materials for filter-free color-imaging sensors owing to their outstanding optoelectronic properties, tunable bandgaps, and suitability for large-scale fabrication. However, producing patterned perovskite films of sufficiently high quality for such applications poses a challenge for existing fabrication methods: using solution processes to prepare patterned perovskite films is complicated, while evaporation methods often result in perovskite photodetectors with limited performance. In this paper, the authors report the development of an improved evaporation method in which substrates are treated with a brominated (3-aminopropyl) triethoxysilane self-assembled monolayer to improve the properties of the patterned perovskite films. The resulting perovskite photodetectors exhibit significantly enhanced photosensitivity and long-term stability (exceeding 100 days). Additionally, the polymer substrates facilitate device flexibility. Finally, perovskites comprising three different halide components, each with a different bandgap, are integrated into a device array using the developed evaporation technology, yielding sensors that enable the discrimination of red, green, and blue colors. Thus, the flexible photosensor arrays can generate colorful images closely resembling perceived patterns, demonstrating reliable color imaging. Therefore, this study successfully demonstrates filter-free color-imaging by integrating high-performance patterned and multicomponent perovskite photodetectors, highlighting the potential of such detectors for advanced optoelectronic applications, including hyperspectral imaging.

18.
J Trace Elem Med Biol ; 68: 126796, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34098241

RESUMO

BACKGROUND: Osteoporosis is frequently accompanied by iron disorders. Calcitonin (CT) was approved as a clinical drug to treat osteoporosis. Hepcidin is a peptide hormone that is secreted by the liver and controls body iron homeostasis. Hepcidin deficiency leads to iron overload diseases. This study was aimed at investigating the effect of CT on hepatic hepcidin and the mechanism by which CT modulates hepatic hepcidin pathways and iron metabolism. METHOD: RT-PCR, Western blot, ELISA and siRNA were used to detect the effect of CT on iron metabolism in vivo and in vitro. In addition, the regulatory signal molecules of hepcidin were measured to explore the molecular mechanism of its regulation. RESULTS: The results showed that CT strongly increased hepcidin expression and altered iron homeostasis, after mice were intraperitoneal injection of CT. In response to CT administration, BMP6 level in kidney and the serum BMP6 was increased significantly. The phosphorylation of Smad1/5/8 proteins in liver was increased at 3 h and 6 h. Moreover, the Bmp inhibitor LDN-193,189 pretreatment significantly attenuated the CT-mediated increases in phosphorylated Smad1/5/8 and Hamp1 mRNA levels. Calcitonin receptor (CTR) siRNA transfection significant suppressed the role of CT on BMP6 expression in Caki-1 cells. CONCLUSION: Our results suggest that CT strongly induces hepcidin expression and affected iron metabolism. It will provide a new strategy for the treatment of calcium iron related diseases.

19.
J Cell Mol Med ; 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34018320

RESUMO

JAK/STAT and NFκB signalling pathways play essential roles in regulating inflammatory responses, which are important pathogenic factors of various serious immune-related diseases, and function individually or synergistically. To find prodrugs that can treat inflammation, we performed a preliminary high-throughput screening of 18 840 small molecular compounds and identified scaffold compound L971 which significantly inhibited JAK/STAT and NFκB driven luciferase activities. L971 could inhibit the constitutive and stimuli-dependent activation of STAT1, STAT3 and IκBα and could significantly down-regulate the proinflammatory gene expression in mouse peritoneal macrophages stimulated by LPS. Gene expression profiles upon L971 treatment were determined using high-throughput RNA sequencing, and significant differentially up-regulated and down-regulated genes were identified by DESeq analysis. The bioinformatic studies confirmed the anti-inflammatory effects of L971. Finally, L971 anti-inflammatory character was further verified in LPS-induced sepsis shock mouse model in vivo. Taken together, these data indicated that L971 could down-regulate both JAK/STAT and NFκB signalling activities and has the potential to treat inflammatory diseases such as sepsis shock.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 260: 119949, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34023551

RESUMO

In this work, the nonadiabatic energy relaxation mechanism of hemicyanines for UV photoprotection were investigated by using the density functional theory (DFT) and time-dependent density functional theory (TDDFT) method for the first time. The absorption spectra and potential energy surfaces (PESs) of four hemicyanines with different positions of substituents were presented. The maximum absorption peaks of the four hemicyanines are located in the UVA region. In addition, all these hemicyanine molecules also have light absorption in both the UVB and UVC regions. At the same time, we found that the trans-cis photoisomerization PESs of all these hemicyanines have a significant conical intersection (CI) point between the first excited state and the ground state. Herein, it was first demonstrated that the UV energy absorbed by the hemicyanines could be dissipated nonadiabatically through the CI point by using the trans-cis photoisomerization dynamics mechanism. This work proves that hemicyanines have the possibility to be applied for UV photoabsorbers, and provides important basis for designing new type of hemicyanines for UV photoprotection.

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