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1.
J Am Chem Soc ; 146(11): 7419-7430, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38447583

RESUMO

The first earth-abundant transition metal Ni-catalyzed highly regio- and enantioselective semihydrogenation of racemic tetrasubstituted allenes via a kinetic resolution process as a challenging task was well established. This protocol furnishes expedient access to a diversity of structurally important enantioenriched tetrasubstituted allenes and chiral allylic molecules with high regio-, enantio-, and Z/E-selectivity. Remarkably, this semihydrogenation proceeded with one carbon-carbon double bond of allenes, which was regioselective complementary to the Rh-catalyzed asymmetric version. Deuterium labeling experiments and density functional theory (DFT) calculations were carried out to reveal the reasonable reaction mechanism and explain the regio-/stereoselectivity.

2.
BMC Med ; 22(1): 16, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38225649

RESUMO

BACKGROUND: Little is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term night shift work exposure and COPD risk, and assess modification effects of genetic predisposition. METHODS: A total of 277,059 subjects who were in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment was obtained, and a weighted COPD-specific genetic risk score (GRS) was constructed. We used Cox proportional hazard models to investigate associations between night shift work and COPD risk, and their interaction with COPD-specific GRS. RESULTS: The cohort study included 277,059 participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During a median follow-up of 12.87 years, we documented 6558 incidents of COPD. From day work, irregular night shifts to regular night shifts, there was an increased trend in COPD incidence (P for trend < 0.001). Compared with day workers, the hazard ratio (HR) and 95% confidence interval (CI) of COPD was 1.28 (1.20, 1.37) for subjects with rarely/sometimes night shifts and 1.49 (1.35, 1.66) for those with permanent night shifts. Besides, the longer durations (especially in subjects with night shifts ≥ 10 years) and increasing monthly frequency of night shifts (in workers with > 8 nights/month) were associated with a higher COPD risk. Additionally, there was an additive interaction between night shifts and genetic susceptibility on the COPD risk. Subjects with permanent night shifts and high genetic risk had the highest risk of COPD (HR: 1.90 [95% CI: 1.63, 2.22]), with day workers with low genetic risk as a reference. CONCLUSIONS: Long-term night shift exposure is associated with a higher risk of COPD. Our findings suggest that decreasing the frequency and duration of night shifts may offer a promising approach to mitigating respiratory disease incidence in night shift workers, particularly in light of individual susceptibility.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Jornada de Trabalho em Turnos , Masculino , Humanos , Pessoa de Meia-Idade , Jornada de Trabalho em Turnos/efeitos adversos , Tolerância ao Trabalho Programado , Estudos de Coortes , Incidência , Estudos Prospectivos , Bancos de Espécimes Biológicos , Biobanco do Reino Unido , Fatores de Risco , Doença Pulmonar Obstrutiva Crônica/epidemiologia
3.
Angew Chem Int Ed Engl ; : e202408195, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38923245

RESUMO

Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki-Hiyama-Kishi (NHK) reaction is a widely used method for the synthesis of allylic alcohols, it suffers from drawbacks such as the use of toxic chromium salts, high amounts of metal reductants, and poor enantiocontrol. To address these limitations, we present a novel approach involving a metallaphotoredox-catalyzed asymmetric NHK reaction for the production of chiral allylic alcohols. This method marries alkenyl (pseudo)halides with aldehydes, leveraging a synergistic blend of a chiral nickel catalyst and a photocatalyst. This innovative technique enables both oxidative addition and insertion just using nickel, diverging significantly from the conventional NHK reaction pathway mediated by nickel and chromium salts. The adoption of this methodology holds immense promise for crafting a spectrum of intricate compounds, particularly those of significance in pharmaceuticals. Detailed experimental investigations have shed light on the metallaphotoredox process, further enhancing our understanding and enabling further advancements.

4.
Curr Issues Mol Biol ; 45(2): 1570-1586, 2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36826046

RESUMO

ATP-binding cassette (ABC) transporters are involved in transporting multiple substrates, such as toxins, and may be important for the survival of Trichoderma when encountering biotic toxins. In this study, genome searching revealed that there are 44 ABC transporters encoded in the genome of Trichoderma asperellum. These ABC transporters were divided into six types based on three-dimensional (3D) structure prediction, of which four, represented by 39 ABCs, are involved in transport and the remaining two, represented by 5 ABCs, are involved in regulating translation. The characteristics of nucleotide-binding domain (NBD) are important in the identification of ABC proteins. Even though the 3D structures of the 79 NBDs in the 44 ABCs are similar, multiple sequence alignment showed they can be divided into three classes. In total, 794 motifs were found in the promoter regions of the 44 ABC genes, of which 541 were cis-regulators related to stress responses. To characterize how their ABCs respond when T. asperellum interact with fungi or plants, T. asperellum was cultivated in either minimal media (MM) control, C-hungry, N-hungry, or poplar medium (PdPap) to simulate normal conditions, competition with pathogens, interaction with pathogens, and interaction with plants, respectively. The results show that 17 of 39 transport ABCs are highly expressed in at least one condition, whereas four of the five translation-regulating ABCs are highly expressed in at least one condition. Of these 21 highly expressed ABCs, 6 were chosen for RT-qPCR expression under the toxin stress of phytopathogen Alternaria alternata, and the results show ABC01, ABC04, ABC05, and ABC31 were highly expressed and may be involved in pathogen interaction and detoxifying toxins from A. alternata.

5.
Chemistry ; 29(26): e202300029, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-36806228

RESUMO

Deep red/near-infrared (NIR, >650 nm) emissive organic luminophores with aggregation-induced emission (AIE) behaviours have emerged as promising candidates for applications in optoelectronic devices and biological fields. However, the molecular design philosophy for AIE luminogens (AIEgens) with narrow band gaps are rarely explored. Herein, we rationally designed two red organic luminophores, FITPA and FIMPA, by considering the enlargement of transition dipole moment in the charge-transfer state and the transformation from aggregation-caused quenching (ACQ) to AIE. The transition dipole moments were effectively enhanced with a "V-shaped" molecular configuration. Meanwhile, the ACQ-to-AIE transformation from FITPA to FIMPA was induced by a methoxy-substitution strategy. The experimental and theoretical results demonstrated that the ACQ-to-AIE transformation originated from a crystallization-induced emission (CIE) effect because of additional weak interactions in the aggregate state introduced by methoxy groups. Owing to the enhanced transition dipole moment and AIE behaviour, FIMPA presented intense luminescence covering the red-to-NIR region, with a photoluminescence quantum yield (PLQY) of up to 38 % in solid state. The promising cell-imaging performance further verified the great potential of FIMPA in biological applications. These results provide a guideline for the development of red and NIR AIEgens through comprehensive consideration of both the effect of molecular structure and molecular interactions in aggregate states.

6.
Nutr Cancer ; 75(4): 1263-1270, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37139873

RESUMO

The effects of sulforaphane on glycolysis and proliferation of SGC7901 and BGC823 gastric carcinoma cell lines were analyzed, and the potential mediating role of the TBX15/KIF2C axis was explored. SGC7901 and BGC823 cells stably over- or underexpressing TBX15 were exposed to sulforaphane, and cell viability was assessed together with the expression of TBX15, KIF2C, and proteins involved in glycolysis, glucose uptake, and lactate production. Overexpressing TBX15 in SGC7901 and BGC823 cells significantly reduced glucose uptake, lactate production, cell viability, expression of KIF2C, and pyruvate kinase M2-mediated (PKM2) glycolysis. These effects were recapitulated by treatment with sulforaphane. The anti-tumor effects of sulforaphane were antagonized by down-regulation of TBX15, up-regulation of KIF2C or addition of a PKM2 agonist. Sulforaphane can reduce cell proliferation and PKM2-mediated glycolysis in gastric carcinoma cells, apparently by activating the TBX15/KIF2C pathway.


Assuntos
Carcinoma , Proteínas de Transporte , Humanos , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Glucose/metabolismo , Glicólise , Cinesinas/metabolismo , Lactatos/metabolismo , Proteínas com Domínio T/metabolismo
7.
J Environ Sci (China) ; 126: 772-783, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36503802

RESUMO

Environmental exposure to crystalline silica particles can lead to silicosis, which is one of the most serious pulmonary interstitial fibrosis around the world. Unfortunately, the exact mechanism on silicosis is unclear, and the effective treatments are lacking to date. In this study, we aim to explore the molecular mechanism by which interleukin-11 (IL-11) affects silica particles-induced lung inflammation and fibrosis. We observed that IL-11 expressions in mouse lungs were significantly increased after silica exposure, and maintained at high levels across both inflammation and fibrosis phase. Immunofluorescent dual staining further revealed that the overexpression of IL-11 mainly located in mouse lung epithelial cells and fibroblasts. Using neutralizing anti-IL-11 antibody could effectively alleviate the overexpression of pro-inflammatory cytokines (i.e., interleukin-6 and tumor necrosis factor-α) and fibrotic proteins (i.e., collagen type I and matrix metalloproteinase-2) induced by silica particles. Most importantly, the expressions of IL-11 receptor subunit α (IL-11Rα), Glycoprotein 130 (GP130), and phosphorylated extracellular signal-regulated kinase (p-ERK) were significantly increased in response to silica, whereas blocking of IL-11 markedly reduced their levels. All findings suggested that the overexpression of IL-11 was involved in the pathological of silicosis, while neutralizing IL-11 antibody could effectively alleviate the silica-induced lung inflammation and fibrosis by inhibiting the IL-11Rα/GP130/ERK signaling pathway. IL-11 might be a promising therapeutic target for lung inflammation and fibrosis caused by silica particles exposure.


Assuntos
Interleucina-11 , Pneumonia , Animais , Camundongos , Dióxido de Silício/toxicidade , Metaloproteinase 2 da Matriz , Pneumonia/induzido quimicamente , Pneumonia/prevenção & controle , Fibrose
8.
Angew Chem Int Ed Engl ; 62(19): e202300743, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-36916783

RESUMO

Transition-metal-catalyzed enantioselective addition of aryl organometallic reagents to imines has emerged as one of the most powerful tools for the formation of optically active diarylmethylamines. Here, we report the first asymmetric reductive (hetero)arylations of imines using aryl and heteroaryl halides enabled by a chiral cobalt-bisphosphine catalyst. This approach shows good functional group compatibility and complements the reported strategy without use of organometallic reagents. Mechanistic investigations supported that aryl-cobalt, instead of an arylzinc reagent, was formed in situ in this reductive aryl-addition event.

9.
Small ; 18(6): e2105017, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35142068

RESUMO

To better exploit all-liquid 3D architectures, it is essential to understand dynamic processes that occur during printing one liquid in a second immiscible liquid. Here, the interfacial assembly and transition of 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (H6 TPPS) over time provides an opportunity to monitor the interfacial behavior of nanoparticle surfactants (NPSs) during all-liquid printing. The formation of J-aggregates of H4 TPPS2- at the interface and the interfacial conversion of the J-aggregates of H4 TPPS2- to H-aggregates of H2 TPPS4- is demonstrated by interfacial rheology and in situ atomic force microscopy. Equally important are the chromogenic changes that are characteristic of the state of aggregation, where J-aggregates are green in color and H-aggregates are red in color. In all-liquid 3D printed structures, the conversion in the aggregate state with time is reflected in a spatially varying change in the color, providing a simple, direct means of assessing the aggregation state of the molecules and the mechanical properties of the assemblies, linking a macroscopic observable (color) to mechanical properties.


Assuntos
Porfirinas , Porfirinas/química , Reologia , Tensoativos/química
10.
World J Surg Oncol ; 20(1): 189, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35676669

RESUMO

BACKGROUND: Preoperative prediction of microvascular invasion (MVI) is critical for treatment strategy making in patients with hepatocellular carcinoma (HCC). We aimed to develop a deep learning (DL) model based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the MVI status and clinical outcomes in patients with HCC. METHODS: We retrospectively included a total of 321 HCC patients with pathologically confirmed MVI status. Preoperative DCE-MRI of these patients were collected, annotated, and further analyzed by DL in this study. A predictive model for MVI integrating DL-predicted MVI status (DL-MVI) and clinical parameters was constructed with multivariate logistic regression. RESULTS: Of 321 HCC patients, 136 patients were pathologically MVI absent and 185 patients were MVI present. Recurrence-free survival (RFS) and overall survival (OS) were significantly different between the DL-predicted MVI-absent and MVI-present. Among all clinical variables, only DL-predicted MVI status and a-fetoprotein (AFP) were independently associated with MVI: DL-MVI (odds ratio [OR] = 35.738; 95% confidence interval [CI] 14.027-91.056; p < 0.001), AFP (OR = 4.634, 95% CI 2.576-8.336; p < 0.001). To predict the presence of MVI, DL-MVI combined with AFP achieved an area under the curve (AUC) of 0.824. CONCLUSIONS: Our predictive model combining DL-MVI and AFP achieved good performance for predicting MVI and clinical outcomes in patients with HCC.


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Microvasos/patologia , Invasividade Neoplásica/patologia , Estudos Retrospectivos , alfa-Fetoproteínas
11.
Ecotoxicol Environ Saf ; 247: 114215, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306621

RESUMO

Silicosis is one of the most severe interstitial lung fibrosis diseases worldwide, caused by crystalline silica exposure. While the mechanisms and pathogenesis underlying silicosis remained unknown. N6-methyladenosine (m6A) methylation has received significant attention in a variety of human diseases. However, whether m6A methylation is involved in silicosis has not been clarified. In this study, we conducted methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and transcriptome sequencing (RNA-Seq) to profile the m6A modification in normal and silicosis mouse models (n = 3 pairs). The global levels of m6A methylation were further assessed by m6A RNA methylation quantification kits, and the major regulators of m6A RNA methylation were verified by qRT-PCR. Our results showed that long-term exposure to crystalline silica led to silicosis, accompanied by increasing levels of m6A methylation. Upregulation of METTL3 and downregulation of ALKBH5, FTO, YTHDF1, and YTHDF3 might contribute to aberrant m6A modification. Compared with controls, 359 genes showed differential m6A methylation peaks in silicosis (P < 0.05 and FC ≥ 2). Among them, 307 genes were hypermethylated, and 52 genes were hypomethylated. RNA-Seq analysis revealed 1091 differentially expressed genes between the two groups, 789 genes were upregulated and 302 genes were downregulated in the lungs of silicosis mice (P < 0.05 and FC ≥ 2). In the conjoint analysis of MeRIP-Seq and RNA-Seq, we identified that 18 genes showed significant changes in both m6A modification and mRNA expression. The functional analysis further noted that these 18 m6A-mediated mRNAs regulated pathways that were closely related to "phagosome", "antigen processing and presentation", and "apoptosis". All findings suggested that m6A methylation played an essential role in the formation of silicosis. Our discovery with multi-omics approaches not only gives clues for the epigenetic mechanisms underlying the pathogenesis of silicosis but also provides novel and viable strategies for the prevention and treatment of silicosis.


Assuntos
Fibrose Pulmonar , Silicose , Humanos , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Transcriptoma , Dióxido de Silício/toxicidade , Metilação , Silicose/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo
12.
Environ Toxicol ; 37(8): 1925-1933, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35438832

RESUMO

Inhalation of crystalline silica (CS) can cause silicosis, which is one of the most serious interstitial lung diseases worldwide. Autophagy dysfunction is an essential step in silicosis progression. In this study, we aim to identify the effect of growth arrest-specific protein 6 (Gas6) during autophagy induction and macrophage inflammatory response caused by CS. After RAW 264.7 macrophages exposed to CS, the levels of Gas6 and autophagy markers (p62, Beclin1, and LC3-II/LC3-I) were increased, accompanied with enhanced inflammatory cytokines secretion. Using autophagy activator (rapamycin) repressed, whereas autophagy inhibitor (3-methyladenine) promoted inflammatory cytokines release. Besides, inhibition of Gas6 aggravated CS-induced inflammatory response, and autophagy inhibition facilitated the promoted effect of Gas6 silencing, resulting in elevated expression of inflammatory cytokines. These findings reveal the protective effects of Gas6 and autophagy in macrophages in response to CS exposure, and highlight the autophagy regulated by Gas6 may be a potential prevention target for CS-induced lung inflammatory response.


Assuntos
Dióxido de Silício , Silicose , Autofagia , Citocinas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Macrófagos , Dióxido de Silício/toxicidade , Silicose/metabolismo
13.
Cardiovasc Ultrasound ; 19(1): 26, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289865

RESUMO

BACKGROUND: Essential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography. METHODS: All patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid-femoral pulse wave velocity (cfPWV), intimal-medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography. RESULTS: The cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E' among three groups. CONCLUSION: Children and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.


Assuntos
Hipertensão , Análise de Onda de Pulso , Adolescente , Criança , Diástole , Ecocardiografia , Hipertensão Essencial , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Função Ventricular Esquerda
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(3): 350-356, 2021 May.
Artigo em Zh | MEDLINE | ID: mdl-34018350

RESUMO

Modern tissue clearing techniques have made it possible to have high-resolution imaging of cell populations and three-dimensional reconstruction of tissue structures, and we are able to obtain more complete three-dimensional brain structures and spatial connections between the various components of brain tissues through tissue clearing techniques. Over the past decade, scientists have developed and improved a number of tissue clearing techniques that are now widely used in neuroscience research, allowing us to extract important information from complex neural networks. Moreover, tissue clearing technology also provides research tools for the stem cell therapy and neurogeneration of neurodegenerative diseases. In this paper, we reviewed the major types of existing tissue clearing techniques and their respective strengths and weaknesses. We summarized the application of these techniques in neurodegenerative disease research and their unique merits. In addition, we explored the development requirements of tissue clearing technology, improvements in the supporting equipment, and its potential to be used as research tools for stem cell therapy and regenerative medicine in the future.


Assuntos
Doenças Neurodegenerativas , Encéfalo , Humanos , Imageamento Tridimensional , Doenças Neurodegenerativas/terapia , Tecnologia
15.
Angew Chem Int Ed Engl ; 60(16): 8694-8699, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33491263

RESUMO

With the interfacial jamming of nanoparticles (NPs), a load-bearing network of NPs forms as the areal density of NPs increases, converting the assembly from a liquid-like into a solid-like assembly. Unlike vitrification, the lineal packing of the NPs in the network is denser, while the remaining NPs can remain in a liquid-like state. It is a challenge to determine the point at which the assemblies jam, since both jamming and vitrification lead to a solid-like behavior of the assemblies. Herein, we show a real-time fluorescence imaging method to probe the evolution of the interfacial dynamics of NP surfactants at the water/oil interface using aggregation-induced emission (AIE) as a reporter for the transition of the assemblies into the jammed state. The AIEgens show typical fluorescence behavior at densities at which they can move and rotate. However, when aggregation of these fluorophores occurs, the smaller intermolecular separation distance arrests rotation, and a significant enhancement in the fluorescence intensity occurs.

16.
Angew Chem Int Ed Engl ; 60(6): 2871-2876, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33111473

RESUMO

Locking nonequilibrium shapes of liquids into targeted architectures by interfacial jamming of nanoparticles is an emerging area in material science. 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (H6 TPPS) shows three different aggregation states that present an absorption imaging platform to monitor the assembly and jamming of supramolecular polymer surfactants (SPSs) at the liquid/liquid interface. The interfacial interconversion of H6 TPPS, specifically H4 TPPS2- dissolved in water, from J- to an H-aggregation was induced by strong electrostatic interactions with amine-terminated polystyrene dissolved in toluene at the water/toluene interface. This resulted in color-tunable liquids due to interfacial jamming of the SPSs formed between H4 TPPS2- and amine-terminated polystyrene. However, the formed SPSs cannot lock in nonequilibrium shapes of liquids. In addition, a self-wrinkling behavior was observed when amphiphilic triblock copolymers of PS-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) were used to interact with H4 TPPS2- . Subsequently, the SPSs formed can lock in nonequilibrium shapes of liquids.

17.
Zhongguo Zhong Yao Za Zhi ; 45(2): 312-320, 2020 Jan.
Artigo em Zh | MEDLINE | ID: mdl-32237313

RESUMO

Gastrodin(GAS) and p-hydroxybenzyl alcohol(HBA) are extracts of dried tubers of Gastrodia elata, which is the material basis for its efficacy and belongs to phenolic compounds. Modern pharmacology studies have shown that they have significant effects on central nervous system diseases, such as insomnia, convulsions, depression, ischemic stroke, anxiety, and cognitive impairment, and these diseases are closely related to neurotransmitters and cytokines. This paper described various mechanisms of GAS and HBA monomer components on the central nervous system. They alleviate hippocampal neuronal toxicity mainly by regulating a variety of neurotransmitters, such as acetylcholine, glutamic acid(GLU), γ-aminobutyric acid(GABA), serotonin(5-HT), dopamine(DA), norepinephrine(NE), 5-indoleacetic acid(5-HIAA), high vanillic acid(HVA) and dihydroxyphenylacetic acid(DOPAC), pro-inflammatory cell growth factors, such as IL-1ß, IL-6 and TNF-α and relevant receptor functions, and exert neuropharmacological effects by effectively increasing mRNA expressions of brain neurotrophic factors, such as BDNF and GDNF, and further inhibiting the apoptosis of damaged neurons. This paper summarized various mechanisms on the central nervous system, which provides a scientific basis for the further research of the neuropharmacological mechanism of GAS and HBA and the development of new drugs and functional food.


Assuntos
Álcoois Benzílicos/farmacologia , Sistema Nervoso Central/efeitos dos fármacos , Glucosídeos/farmacologia , Extratos Vegetais/farmacologia , Gastrodia/química , Humanos
18.
Angew Chem Int Ed Engl ; 58(35): 12112-12116, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31353804

RESUMO

The strong electrostatic interactions at the oil-water interface between a small molecule, 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin, H6 TPPS, dissolved in water, and an amine terminated hydrophobic polymer dissolved in oil are shown to produce a supramolecular polymer surfactant (SPS) of H6 TPPS at the interface with a binding energy that is sufficiently strong to allow an intermolecular aggregation of the supramolecular polymers. SPSs at the oil-water interface are confirmed by in situ real-space atomic force microcopy imaging. The assemblies of these aggregates can jam at the interface, opening a novel route to kinetically trap the liquids in non-equilibrium shapes. The elastic film, comprised of SPSs, wrinkles upon compression, providing a strategy to stabilize liquids in non-equilibrium shapes.

19.
Med Sci Monit ; 23: 3209-3216, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28667247

RESUMO

BACKGROUND Mesenchymal stem cells (MSCs) have emerged as an attractive alternative to modulating immune response after transplantation. Recent studies have shown that systemically administered MSCs enter the inflamed intestine. In the present study, we propose a strategy to improve the efficacy of MSC-based cellular therapy for inflammation using Astragaloside and Baicalein to enhance cell survival, inhibit apoptosis, and modulate inflammatory response in vitro. MATERIAL AND METHODS MSCs were induced with lipopolysaccharide (LPS) as an inflammatory model before being treated for 48 h with Astragaloside, Baicalein, and the combination of both. MSCs proliferation was determined using the MTT method. The cell cycle situation was monitored using flow cytometry, and the apoptosis ability of MSCs was detected with Annexin-V flow cytometry. The levels of cytokine IL-1ß, IL-8, and TNF-α, and their relations with the ERK pathway were measured using ELISA, RT-PCR, and Western blot. RESULTS Compared to the control groups (containing no drug), each drug-treated group showed the ability to promote epithelial differentiation and cell growth and to inhibit apoptosis. The combination group had reduced levels of IL-1ß, IL-8, and TNF-α in LPS-induced MSCs, much more than in the other 2 groups. Compared with the other groups, the combination of Astragaloside and Baicalin more efficiently reduced IL-1ß, IL-8, and TNF-α levels in the LPS-induced MSCs model, and ERK inhibitor was capable of recovering the inflammatory effect. CONCLUSIONS The results demonstrated that Astragaloside and Baicalin can promote epithelial differentiation and proliferation, inhibit apoptosis, and reduce inflammatory effects.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Flavanonas/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/enzimologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/patologia , Saponinas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Separação Celular , Citocinas/metabolismo , Flavanonas/farmacologia , Inflamação/patologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/enzimologia , Ratos Sprague-Dawley
20.
Biol Pharm Bull ; 39(9): 1412-8, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27334578

RESUMO

Vinpocetine is an inhibitor of phosphodiesterase type 1 (PDE1), which has been used for treating stroke for over 40 years. However, according to current clinical dosage and treatment period, its direct effect on memory is unclear. In this study, we investigated whether vinpocetine could reverse the scopolamine (SCO)-induced cognitive deficits in animals. Behavioral experiments, including open field, Y-maze, and fear conditioning tests were used to determine the possible role of vinpocetine on scopolamine-induced memory dysfunction. In the open field and Y-maze tests, there were significant differences between the control (CON) group and SCO group. Vinpocetine (4 mg/kg) administration for consecutive 28 d significantly improved the scopolamine-induced memory dysfunction. In the fear conditioning test, vinpocetine (2, 4 mg/kg) administration had certain beneficial effect on emotional memory. Our results suggest that vinpocetine could improve cognitive function in memory deficient mice and high clinic dosage might be better.


Assuntos
Demência/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Alcaloides de Vinca/uso terapêutico , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Condicionamento Psicológico/efeitos dos fármacos , Demência/induzido quimicamente , Medo , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Camundongos Endogâmicos C57BL , Escopolamina
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