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1.
Molecules ; 29(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731488

RESUMO

This study synthesized a novel oat ß-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.


Assuntos
Cromo , Hipoglicemiantes , alfa-Glucosidases , beta-Glucanas , Humanos , Cromo/química , Cromo/farmacologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , beta-Glucanas/química , beta-Glucanas/farmacologia , Células Hep G2 , alfa-Glucosidases/metabolismo , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , Resistência à Insulina , Glucose/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Avena/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química
2.
J Vasc Res ; 60(4): 183-192, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37660689

RESUMO

OBJECTIVE: The aim of the study was to evaluate the effect of the RhoA/ROCK inhibitor Fasudil on retinal neovascularization (NV) in vivo and angiogenesis in vitro. METHODS: C57BL/6 was used to establish an OIR model. First, RhoA/ROCK expression was first examined and compared between OIR and healthy controls. Then, we evaluated the effect of Fasudil on pathological retinal NV. Whole-mount retinal staining was performed. The percentage of NV area, the number of neovascular tufts (NVT), and branch points (BP) were quantified. Finally, human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of Fasudil on angiogenesis. RESULTS: Real-time PCR and Western blotting showed that ROCK expression in retinal tissue was statistically upregulated in OIR. Furthermore, we found that Fasudil attenuated the percentage of NV area, the number of NVT, and BP significantly. In addition, Fasudil could suppress the proliferation and migration of HUVECs induced by VEGF. CONCLUSIONS: RhoA/ROCK might be involved in the pathogenesis of OIR. And its inhibitor Fasudil could suppress retinal NV in vivo and angiogenesis in vitro. Fasudil may be a potential treatment strategy for retinal vascular diseases.


Assuntos
Neovascularização Retiniana , Humanos , Animais , Camundongos , Neovascularização Retiniana/genética , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Neovascularização Patológica/patologia , Retina/metabolismo , Células Endoteliais da Veia Umbilical Humana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
3.
Opt Lett ; 48(6): 1498-1501, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36946962

RESUMO

In this Letter, we demonstrate a high-sensitivity vector bend sensor based on a fiber directional coupler. The fiber directional coupler is composed of two parallel waveguides inscribed within a no-core fiber (NCF) by a femtosecond laser. Since the two written waveguides have closely matched refractive indices and geometries, the transmission spectrum of the fiber directional coupler possesses periodic resonant dips. Such a fiber directional coupler exhibits a good bending-dependent spectral shift response due to its asymmetric structure. Experimental results show that bending sensitivities of -97.11 nm/m-1 and 58.22 nm/m-1 are achieved for the 0° and 180° orientations in the curvature range of 0-0.62 m-1, respectively. In addition, the proposed fiber directional coupler is shown to be insensitive to external humidity changes, thus improving its suitability in high-accuracy bending measurements.

4.
Mol Biol Rep ; 50(12): 10277-10285, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37971567

RESUMO

BACKGROUND: Recent reports suggest that peroxisome proliferator-activated receptor-γ (PPAR-γ) could promote microglial M2 polarization to inhibit inflammation. However, the specific molecular mechanisms that trigger PPAR-γ's anti-inflammatory ability in microglia are yet to be expounded. Thus, in this study, we aimed to explore the molecular mechanisms behind the anti-inflammatory effects of PPAR-γ in hypoxia-stimulated rat retinal microglial cells. METHODS AND RESULTS: We used shRNA expressing lentivirus to knock down PPAR-γ and CD200 genes, and we assessed hypoxia-induced polarization markers release - M1 (iNOS, IL-1ß, IL-6, and TNF-α) and M2 (Arg-1, YM1, IL-4, and IL-10) by RT-PCR. We also monitored PPAR-γ-related signals (PPAR-γ, PPAR-γ in cytoplasm or nucleus, CD200, and CD200Rs) by Western blot and RT-PCR. Our results showed that hypoxia enhanced PPAR-γ and CD200 expressions in microglial cells. Moreover, PPAR-γ agonist 15d-PGJ2 elevated CD200 and CD200R1 expressions, whereas sh-PPAR-γ had the opposite effect. Following hypoxia, expressions of M1 markers increased significantly, while those of M2 markers decreased, and the above effects were attenuated by 15d-PGJ2. Conversely, knocking down PPAR-γ or CD200 inhibited the polarization of microglial cells to M2 phenotype. CONCLUSION: Our findings demonstrated that PPAR-γ performed an anti-inflammatory function in hypoxia-stimulated microglial cells by promoting their polarization to M2 phenotype via the CD200-CD200R1 pathway.


Assuntos
Microglia , PPAR gama , Animais , Ratos , Anti-Inflamatórios/farmacologia , Hipóxia/genética , Hipóxia/metabolismo , Microglia/metabolismo , Fenótipo , PPAR gama/genética , PPAR gama/metabolismo
5.
Immunopharmacol Immunotoxicol ; 45(4): 433-442, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36617937

RESUMO

OBJECTIVE: To explore the effect of baicalin on human nucleus pulposus cells (NPCs) in response to interleukin (IL)-1ß stimulation. METHODS: Viability of NPCs was measured by cell counting kit-8 (CCK-8) assay. TUNEL staining assay and flow cytometry were performed to detect apoptotic cell death of NPCs. Western blot analysis was conducted to detect the expression levels of proteins. Enzyme-linked immunosorbent assay (ELISA) was applied for the determination of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and IL-6. Oxidative stress indicators including reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity were measured. RESULTS: Baicalin attenuated IL-1ß-caused cell viability reduction and apoptosis in NPCs. IL-1ß-induced increase in Bax expression and decrease in Bcl-2 expression were attenuated by baicalin treatment. IL-1ß-induced production of iNOS, COX-2, IL-6, and TNF-α in NPCs was inhibited by baicalin treatment. Baicalin treatment reversed IL-1ß-induced increase in ROS production and MDA level, as well as decrease in SOD activity. Furthermore, baicalin treatment elevated the expression levels of Col II and Aggrecan and downregulated the expression levels of MMP3, MMP13, and ADAMTS5 in IL-1ß-induced NPCs. A total of 402 related targets of baicalin and 134 related targets of intervertebral disk degeneration were found, and nine intersection targets were screened out. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that mitogen-activated protein kinase (MAPK) pathway was found to be involved in the effects of baicalin. CONCLUSIONS: Baicalin exhibited protective effects on IL-1ß-caused cell viability reduction, apoptosis, oxidative stress, inflammation, and extracellular matrix degradation in NPCs. In addition, we found c-Jun N-terminal kinase (JNK) and p38 MAPK pathways as targets of baicalin through bioinformatic analysis.


Assuntos
Apoptose , Flavonoides , Núcleo Pulposo , Humanos , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Matriz Extracelular/metabolismo , Flavonoides/farmacologia , Interleucina-1beta/farmacologia , Interleucina-6/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Estresse Oxidativo , Piroptose , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Sistema de Sinalização das MAP Quinases
6.
Sensors (Basel) ; 23(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36850875

RESUMO

Mobile crowdsensing (MCS) has been an emerging sensing paradigm in recent years, which uses a sensing platform for real-time processing to support various services for the Internet of Things (IoT) and promote the development of IoT. As an important component of MCS, how to design task assignment algorithms to cope with the coexistence of multiple concurrent heterogeneous tasks in group-oriented social relationships while satisfying the impact of users' preferences on heterogeneous multitask assignment and solving the preference matching problem under heterogeneous tasks, is one of the most pressing issues. In this paper, a new algorithm, group-oriented adjustable bidding task assignment (GO-ABTA), is considered to solve the group-oriented bilateral preference-matching problem. First, the initial leaders and their collaborative groups in the social network are selected by group-oriented collaboration, and then the preference assignment of task requesters and users is modeled as a stable preference-matching problem. Then, a tunable bidding task assignment process is completed based on preference matching under budget constraints. Finally, the individual reasonableness, stability, and convergence of the proposed algorithm are demonstrated. The effectiveness of the proposed algorithm and its superiority to other algorithms are verified by simulation results.

7.
Med Anthropol Q ; 37(2): 148-163, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36989348

RESUMO

China and India have become major producers of antibiotics, and the world has become highly dependent on them. Since 2000, the competition among Chinese and Indian manufacturers on key antibiotic ingredients has become increasingly intense in a series of trade disputes involving anti-dumping investigations. Analyzing these trade disputes, we find that they provide a space of communication and contestation where seemingly objective facts about pharmaceutical ingredients are transformed into debatable subjects, which are used and sometimes manipulated by stakeholders of conflicting interests. The disputes reveal entangled configurations and multilayered stakes in the China-India pharmaceutical nexus that often defy polarized national interests. Stakeholders must juggle multiple factors, including public health interests, nationalist sentiments, and corporate profit, in negotiating the national identities and the physical and chemical properties of "standard" pharmaceutical ingredients. The disputes also highlight the coexistence of collaboration and competition among Chinese and Indian stakeholders in global pharmaceutical supply chains. [antibiotics, active pharmaceutical ingredients (APIs), pharmaceutical nexus, dumping, trade disputes, China-India].


Assuntos
Dissidências e Disputas , Negociação , Humanos , Antropologia Médica , Índia , China , Preparações Farmacêuticas
8.
Angew Chem Int Ed Engl ; 62(50): e202313868, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37899658

RESUMO

Solar-to-chemical energy conversion under weak solar irradiation is generally difficult to meet the heat demand of CO2 reduction. Herein, a new concentrated solar-driven photothermal system coupling a dual-metal single-atom catalyst (DSAC) with adjacent Ni-N4 and Fe-N4 pair sites is designed for boosting gas-solid CO2 reduction with H2 O under simulated solar irradiation, even under ambient sunlight. As expected, the (Ni, Fe)-N-C DSAC exhibits a superior photothermal catalytic performance for CO2 reduction to CO (86.16 µmol g-1 h-1 ), CH4 (135.35 µmol g-1 h-1 ) and CH3 OH (59.81 µmol g-1 h-1 ), which are equivalent to 1.70-fold, 1.27-fold and 1.23-fold higher than those of the Fe-N-C catalyst, respectively. Based on theoretical simulations, the Fermi level and d-band center of Fe atom is efficiently regulated in non-interacting Ni and Fe dual-atom pair sites with electronic interaction through electron orbital hybridization on (Ni, Fe)-N-C DSAC. Crucially, the distance between adjacent Ni and Fe atoms of the Ni-N-N-Fe configuration means that the additional Ni atom as a new active site contributes to the main *COOH and *HCO3 dissociation to optimize the corresponding energy barriers in the reaction process, leading to specific dual reaction pathways (COOH and HCO3 pathways) for solar-driven photothermal CO2 reduction to initial CO production.

9.
J Cell Mol Med ; 26(1): 88-98, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34854218

RESUMO

Vasorin (VASN) is an important transmembrane protein associated with development and disease. However, it is not clear whether the death of mice with VASN deficiency (VASN-/- ) is related to cardiac dysfunction. The aim of this research was to ascertain whether VASN induces pathological cardiac hypertrophy by targeting myosin light chain 7 (MYL7). VASN-/- mice were produced by CRISPR/Cas9 technology and inbreeding. PCR amplification, electrophoresis, real-time PCR and Western blotting were used to confirm VASN deficiency. Cardiac hypertrophy was examined by blood tests, histological analysis and real-time PCR, and key downstream factors were identified by RNA sequencing and real-time PCR. Western blotting, immunohistochemistry and electron microscopy analysis were used to confirm the downregulation of MYL7 production and cardiac structural changes. Our results showed that sudden death of VASN-/- mice occurred 21-28 days after birth. The obvious increases in cardiovascular risk, heart weight and myocardial volume and the upregulation of hypertrophy marker gene expression indicated that cardiac hypertrophy may be the cause of death in young VASN-/- mice. Transcriptome analysis revealed that VASN deficiency led to MYL7 downregulation, which induced myocardial structure abnormalities and disorders. Our results revealed a pathological phenomenon in which VASN deficiency may lead to cardiac hypertrophy by downregulating MYL7 production. However, more research is necessary to elucidate the underlying mechanism.


Assuntos
Proteínas Reguladoras de Apoptose , Cardiomegalia , Proteínas de Membrana , Cadeias Leves de Miosina , Animais , Proteínas Reguladoras de Apoptose/genética , Western Blotting , Cardiomegalia/genética , Perfilação da Expressão Gênica , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Miócitos Cardíacos/metabolismo , Cadeias Leves de Miosina/genética , Cadeias Leves de Miosina/metabolismo , Regulação para Cima
10.
J Card Fail ; 28(1): 13-20, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34324927

RESUMO

BACKGROUND: Atrial fibrillation (AF) frequently complicates heart failure (HF), and each is associated with lower overall health-related quality of life. We aimed to quantify the incremental burden of AF on the health-related quality of life of patients with HF in clinical practice. METHODS AND RESULTS: We used data from the Utah mEVAL program to analyze patient-reported outcomes (PROs) among patients with HF with and without AF. The primary outcome was the HF-specific Kansas City Cardiomyopathy Questionnaire, with generic PROs as secondary outcomes. Among 1707 patients with HF, 36% had AF (n = 616). Those with HF and AF were older (mean age 69 years vs 58 years, P < .001), more likely to have prior stroke (29% vs 17%, P < .001) and ischemic cardiomyopathy (28% vs 23%, P = .01), but had similar ejection fractions (mean 44% each, P = .6). After adjustment, and compared with HF alone, HF with AF was associated with worse Kansas City Cardiomyopathy Questionnaire scores (adjusted mean difference -3.45, 95% confidence interval [CI] -6.24 to -0.65), and worse Patient-Reported Outcomes Measurement Information System physical function scores (adjusted mean difference -1.63, 95% CI -2.59 to -0.67). The difference in visual analog scale general health was borderline (adjusted mean difference -2.01, 95% CI -4.51 to 0.49), and Patient-Reported Outcomes Measurement Information System depression scores were similar (adjusted mean difference 0.54, 95% CI -0.48 to 1.57). CONCLUSIONS: AF complicates nearly one-third of HF cases, and patients with HF and AF are substantially older and sicker. After adjustment, AF was independently associated with worse disease-specific and overall health-related quality of life than HF alone. Whether maintaining sinus rhythm can improve the HF-related health status of patients with HF in clinical practice should be explored further.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Medidas de Resultados Relatados pelo Paciente , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Volume Sistólico , Utah/epidemiologia , Valina/análogos & derivados
11.
Inflamm Res ; 71(4): 397-407, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35275225

RESUMO

PURPOSE: Our study aimed to investigate the function of Cavin-1 and SOCS3 in macrophages/microglia M2 polarization and further explored the relevant mechanism. METHODS: Expression levels of Cavin-1 and SOCS3 in macrophages/microglia were measured by western blotting and RT-PCR, respectively. Then, Cavin-1 or SOCS3 was gene silenced by a siRNA approach, and gene silencing efficiency was determined by western blotting. Next, co-immunoprecipitation (Co-IP) was employed to further analyze the interaction between Cavin-1 and SOCS3. Finally, the activation of STAT6/PPAR-γ signaling was evaluated using western blotting, and the M2 macrophages/microglia polarization was validated by measuring the mRNA expression of M2 markers by RT-PCR. RESULTS: In the polarization process of macrophages/microglia to M2 phenotype, both Cavin-1 and SOCS3 increased synchronously at protein and mRNA level, reached the peak at the 6 h, and then decreased. After Cavin-1 or SOCS3 silencing, the expression of Cavin-1 and SOCS3 declined. These results suggested that Cavin-1 and SOCS3 were positively correlated in macrophages/microglia, and this conjecture was verified by Co-IP. Besides, Cavin-1 silencing not only suppressed the activation of STAT6/PPAR-γ pathway, but also suppressed the release of anti-inflammatory factors. Finally, we found that SOCS3 overexpression reversed the inhibitory effect of Cavin-1 silencing on the release of anti-inflammatory factors in M2 macrophages/microglia. CONCLUSIONS: Cavin-1 and SOCS3 are actively involved in the process of M2 macrophages/microglia polarization. As a SOCS3 interacting protein, Cavin-1 can promote M2 macrophages/microglia polarization via SOCS3.


Assuntos
Microglia , Receptores Ativados por Proliferador de Peroxissomo , Anti-Inflamatórios/farmacologia , Macrófagos , Microglia/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro/metabolismo
12.
J Org Chem ; 87(9): 6378-6386, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35422116

RESUMO

Although direct acetoxylation and cyclization of alkylamide have been extensively reported, investigation of the structural influence of directing groups on selectivity is limited. Pd-catalyzed 2-methoxyiminoacyl (MIA) assisted γ-acetoxylation of alkylamides has been developed. Further DFT studies have demonstrated that the directing groups have a significant influence on the reductive elimination step. The strong electron-donating effect of the OMe group in MIA leads to the preferential formation of a five-membered cyclopalladium (OAc-Pd-C) complex, which favors the acetoxylation pathway.

13.
Mol Biol Rep ; 49(10): 9335-9344, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35945403

RESUMO

BACKGROUND: Lung injury caused by pulmonary inflammation is one of the main manifestations of respiratory diseases. Vasorin (VASN) is a cell-surface glycoprotein encoded by the VASN gene and is expressed in the lungs of developing mouse foetuses. Previous research has revealed that VASN is associated with many diseases. However, its exact function in the lungs and the underlying mechanism remain poorly understood. METHODS AND RESULTS: To investigate the molecular mechanisms involved in lung disease caused by VASN deficiency, a VASN gene knockout (VASN-/-) model was established. The pathological changes in the lungs of VASN-/- mice were similar to those in a lung injury experimental mouse model. We further analysed the transcriptomes of the lungs of VASN-/- mice and wild-type mice. Genes in twenty-four signalling pathways were enriched in the lungs of VASN-/- mice, among which PPAR signalling pathway genes (3 genes, FABP4, Plin1, AdipoQ, were upregulated, while apoA5 was downregulated) were found to be closely related to lung injury. The most significantly changed lung injury-related gene, FABP4, was selected for further verification. The mRNA and protein levels of FABP4 were significantly increased in the lungs of VASN-/- mice, as were the mRNA and protein levels of the inflammatory factors IL-6, TNF-α and IL-1ß. CONCLUSIONS: We believe that these data provide molecular evidence for the regulatory role of VASN in inflammation in the context of lung injury.


Assuntos
Lesão Pulmonar , Animais , Proteínas Reguladoras de Apoptose , Proteínas de Ligação a Ácido Graxo , Inflamação/genética , Interleucina-6/metabolismo , Pulmão/metabolismo , Lesão Pulmonar/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro , Fator de Necrose Tumoral alfa/metabolismo
14.
Opt Lett ; 46(22): 5595-5598, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780414

RESUMO

An ultra-compact in-core-parallel-written fiber Bragg grating (FBG) and Mach-Zehnder interferometer (MZI) for simultaneous measurement of strain and temperature is described. The FBG and MZI are written spatially parallel in the same section of fiber core using a femtosecond laser, forming an ultra-compact device, which is different from the previously developed axial cascade of different structures. Due to the weak coupling between the FBG and the MZI, their individual extinction ratios are traded off by optimizing their writing position and separation, and extinction ratios of 5.9 dB for the FBG and 10 dB for the MZI are achieved. Experimental results show that the FBG and MZI have different sensitivities for strain and temperature, allowing this device to measure strain and temperature simultaneously. In addition, since both the FBG and MZI are written in the fiber core, this ultra-compact device is proven to be impervious to ambient humidity, making it a promising candidate for accurate industrial strain and temperature measurements.

15.
Chem Res Toxicol ; 34(4): 1016-1023, 2021 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-33728903

RESUMO

Stroke is a significant cardiovascular disease that influences the health of human beings all over the world, especially the elderly population. It is reported that the blood-brain barrier (BBB) can be easily destroyed by stroke, which is one of the main factors responsible for macrophage infiltration and central nervous inflammation. Here, we report the protective effects of Trelagliptin against BBB injury and macrophage infiltration. Our results indicate that the infraction volume, the neurological score, and macrophage infiltration staining with CD68 were increased in middle cerebral artery occlusion (MCAO) mice but significantly reversed by treatment with Trelagliptin. Additionally, Trelagliptin reduced the permeability of the BBB by increasing the expression of the tight junction zonula occludens protein-1 (ZO-1) in the cerebral cortex. In an in vitro hypoxia model of endothelial cells, the increased migration of macrophages, enlarged permeability of endothelial monolayer, downregulation of ZO-1, and elevated expression level of CXCL1 by hypoxic conditions were all reversed by treatment with Trelagliptin in a dose-dependent manner. Our results demonstrate that Trelagliptin might mitigate macrophage infiltration by preventing the breakdown of the blood-brain barrier in the brains of MCAO mice.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/prevenção & controle , Macrófagos/efeitos dos fármacos , Uracila/análogos & derivados , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Uracila/química , Uracila/farmacologia
16.
Langmuir ; 37(9): 2954-2962, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33636083

RESUMO

Low molecular weight gelators (LMWG) have been extensively explored in many research fields due to their unique reversible gel-sol transformation. Intermolecular interactions between LMWG are known as the main driving force for self-assembly. During this self-assembly process, individually analyzing the contribution difference between various intermolecular interactions is crucial to understand the gel properties. Herein, we report 2,5-bis(hexadecylcarbamoyl)terephthalic acid (BHTA) as a LMWG, which could efficiently form a stable organogel with n-hexadecane, diesel, liquid paraffin, and base lubricant oil at a relatively low concentration. To investigate the contribution difference of intermolecular interactions, we first finished FT-IR spectroscopy and XRD experiments. On the basis of the d-spacing, a crude simulation model was built and then subjected to molecular dynamics (MD) simulations. Then, we knocked out the energy contribution of the H-bonding interactions and π-π stacking, respectively, to evaluate the intermolecular interactions significantly influencing the stability of the gel system. MD simulations results suggest that the self-assembly of the aggregates was mainly driven by dense H-bonding interactions between carbonyl acid and amide moieties of BHTA, which is consistent with FT-IR data. Moreover, wave function analysis at a quantum level suggested these electrostatic interactions located in the middle of the BHTA molecule were surrounded by strong dispersion attraction originating from a hydrophobic environment. Furthermore, we also confirmed that 2 wt % BHTA was able to form gel lubricant with 150BS. The coefficient of friction (COF) data show that the gel lubricant has a better tribological performance than 150BS base lubricant oil. Finally, XPS was performed and offered valuable information about the lubrication mechanism during the friction.

17.
Mol Biol Rep ; 48(3): 2803-2815, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33730288

RESUMO

Chronic liver diseases are attributed to liver injury. Development of fibrosis from chronic liver diseases is a dynamic process that involves multiple molecular and cellular processes. As the first to be impacted by injury, liver sinusoidal endothelial cells (LSECs) are involved in the pathogenesis of liver diseases caused by a variety of etiologies. Moreover, capillarization of LSECs has been recognized as an important event in the development of chronic liver diseases and fibrosis. Studies have reported that various cytokines (such as vascular endothelial growth factor, transforming growth factor-ß), and pathways (such as hedgehog, and Notch), as well as epigenetic and metabolic factors are involved in the development of LSEC-mediated liver fibrosis. This review describes the complexity and plasticity of LSECs in fibrotic liver diseases from several perspectives, including the cross-talk between LSECs and other intra-hepatic cells. Moreover, it summarizes the mechanisms of several kinds of LSECs-targeting anti-fibrosis chemicals, and provides a theoretical basis for future studies.


Assuntos
Células Endoteliais/patologia , Cirrose Hepática/patologia , Fígado/patologia , Animais , Citocinas/metabolismo , Epigênese Genética , Humanos , Cirrose Hepática/genética , Mecanotransdução Celular
18.
J Gastroenterol Hepatol ; 36(3): 767-774, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32840326

RESUMO

BACKGROUND AND AIM: Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. METHODS: The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). RESULTS: We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). CONCLUSIONS: In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.


Assuntos
Antivirais/uso terapêutico , Estudos de Associação Genética , Genótipo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Anemia/induzido quimicamente , Antivirais/efeitos adversos , Povo Asiático/genética , China , Feminino , Hepatite C Crônica/fisiopatologia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Resposta Viral Sustentada , Resultado do Tratamento
19.
Int J Med Sci ; 18(2): 441-447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390813

RESUMO

Papillary thyroid carcinoma (PTC) is the major subtype of thyroid cancer, accounting for 75%-85% of all thyroid malignancies. This study aimed to identify the association between the interactions of single nucleotide polymorphisms (SNPs) in RAS family genes and PTC in the Han Chinese population, to provide clues to the pathogenesis and potential therapeutic targets for PTC. Hap Map and NCBI-db SNP databases were used to retrieve SNPs. Haploview 4.2 software was used to filter SNPs based on specific parameters, six SNPs of RAS gene (KRAS-rs12427141, KRAS-rs712, KRAS-rs7315339, HRAS-rs12628, NRAS-rs14804 and NRAS-rs2273267) were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) in 673 PTC patients and 657 healthy controls, the interactive effect was evaluated by crossover analysis, logistic regression and GMDR software. We found that genetic mutation in rs712 have significant associations with PTC risk after Bonferroni correction (p<0.001). The interaction between KRAS-rs12427141 and HRAS-rs12628 increased the risk of PTC (U=-2.119, p<0.05), the interaction between KRAS-rs2273267 and HRAS-rs7315339 reduced the risk of PTC (U=2.195, p<0.05). GMDR analysis showed that the two-factor model (KRAS-rs712, NRAS-rs2273267) was the best (p=0.0107). Summarily, there are PTC-related interactions between RAS family genes polymorphisms in the Han Chinese population.


Assuntos
GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , Estudos Cross-Over , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo de Nucleotídeo Único , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
20.
Sensors (Basel) ; 21(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34451038

RESUMO

With the rapid development of deep learning, computer vision has assisted in solving a variety of problems in engineering construction. However, very few computer vision-based approaches have been proposed on work productivity's evaluation. Therefore, taking a super high-rise project as a research case, using the detected object information obtained by a deep learning algorithm, a computer vision-based method for evaluating the productivity of assembling reinforcement is proposed. Firstly, a detector that can accurately distinguish various entities related to assembling reinforcement based on CenterNet is established. DLA34 is selected as the backbone. The mAP reaches 0.9682, and the speed of detecting a single image can be as low as 0.076 s. Secondly, the trained detector is used to detect the video frames, and images with detected boxes and documents with coordinates can be obtained. The position relationship between the detected work objects and detected workers is used to determine how many workers (N) have participated in the task. The time (T) to perform the process can be obtained from the change of coordinates of the work object. Finally, the productivity is evaluated according to N and T. The authors use four actual construction videos for validation, and the results show that the productivity evaluation is generally consistent with the actual conditions. The contribution of this research to construction management is twofold: On the one hand, without affecting the normal behavior of workers, a connection between construction individuals and work object is established, and the work productivity evaluation is realized. On the other hand, the proposed method has a positive effect on improving the efficiency of construction management.


Assuntos
Aprendizado Profundo , Algoritmos , Eficiência , Humanos
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