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2.
Zhongguo Zhong Yao Za Zhi ; 46(3): 526-531, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645016

RESUMO

Mechanism study was performed to explore how Shouhui Tongbian Capsules promotes energy metabolism of gastrointestinal stromal cells. In this study, gastrointestinal stromal cells line GIST-882 was used as the model to explore energy metabolism regulation effects of Shouhui Tongbian Capsules extract(10, 20, 50 and 100 µg·mL~(-1)) by measuring the cell proliferation, ATP level, mitochondrial membrane potential, and mitochondrial isocitrate dehydrogenase activity. Meanwhile, Western blot was used to detect the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Our results showed that Shouhui Tongbian Capsules promoted cell proliferation and increased ATP level of gastrointestinal stromal cells. In addition, Shouhui Tongbian Capsules obviously improved mitochondrial structural integrity, and increased mitochondrial membrane potential in GIST-882 cells. Mechanism study revealed that Shouhui Tongbian Capsules increased mitochondrial isocitrate dehydrogenase activity and up-regulated the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Collectively, our study indicated that Shouhui Tongbian Capsules promoted the energy metabolism for gastrointestinal stromal cells proliferation by activating mitochondrial isocitrate dehydrogenase to induce ATP production, as well as activating SCF/c-Kit and CDK2/cyclin A signaling pathways.


Assuntos
Tumores do Estroma Gastrointestinal , Cápsulas , Linhagem Celular Tumoral , Metabolismo Energético , Humanos , Proteínas Proto-Oncogênicas c-kit/metabolismo , Células Estromais/metabolismo
3.
Zhongguo Zhong Yao Za Zhi ; 46(4): 894-901, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645094

RESUMO

To study the molecular mechanism of Mahuang Lianqiao Chixiaodou Decoction in the treatment of eczema by means of network pharmacology and molecular docking. First, the TCMSP database was used to excavate the active ingredient of each drug in Mahuang Lianqiao Chixiaodou Decoction and predict its target, and the Uniprot database was used to standardize the names of target proteins, in order to obtain the disease targets of eczema through GeneCards, OMIM, PharmGkb, DrugBank and other databases. And next, the potential targets on which drug targets and disease targets work together were selected to make a Venn diagram, the Cytoscape 3.6.1 software was used to screen out and construct the "active ingredient-core targets" network. STRING database was used to construct a protein-protein interaction(PPI) network, and the R language was used to perform GO enrichment analysis and KEGG pathway analysis. Finally, the molecular docking verification of main active ingredients and core targets of the drug was performed by AutoDock software. The study showed that 74 active ingredients and 103 targets of Mahuang Lianqiao Chixiaodou Decoction for the treatment of eczema were screened. The main active ingredients included quercetin, luteolin, wogonin, kaempferol, and the main targets included PTGS1, ESR1, PPARG, and MAPK3. In addition, eight key targets, including MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1 and RELA, were calculated by PPI network. GO enrichment analysis involved 2 024 biological processes, 81 cell components, and 140 molecular functions. KEGG pathway enrichment analysis was performed to screen out 158 eczema-related pathways, which mainly acted on AGE-RAGE signaling pathway, IL-17 signaling pathway, virus-related pathways, and the results of molecular docking showed that the main active compounds could respectively bind to representative targets and exhibit a good affinity. The study proved that the treatment of eczema with Mahuang Lianqiao Chixiaodou Decoction involved multiple signaling pathways and biological processes, and the combination of main active ingredients(such as quercetin, luteolin, wogonin, kaempferol) and key targets(such as MAPK8, MAPK3, JUN, MAPK14, TP53, MAPK1, ESR1, RELA) may be one of the important mechanisms of action.


Assuntos
Medicamentos de Ervas Chinesas , Eczema , Ephedra sinica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Simulação de Acoplamento Molecular , Tecnologia
4.
Signal Transduct Target Ther ; 6(1): 71, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33602894

RESUMO

Mitochondrial fusion/fission dynamics plays a fundamental role in neuroprotection; however, there is still a severe lack of therapeutic targets for this biological process. Here, we found that the naturally derived small molecule echinacoside (ECH) significantly promotes mitochondrial fusion progression. ECH selectively binds to the previously uncharacterized casein kinase 2 (CK2) α' subunit (CK2α') as a direct cellular target, and genetic knockdown of CK2α' abolishes ECH-mediated mitochondrial fusion. Mechanistically, ECH allosterically regulates CK2α' conformation to recruit basic transcription factor 3 (BTF3) to form a binary protein complex. Then, the CK2α'/BTF3 complex facilitates ß-catenin nuclear translocation to activate TCF/LEF transcription factors and stimulate transcription of the mitochondrial fusion gene Mfn2. Strikingly, in a mouse middle cerebral artery occlusion (MCAO) model, ECH administration was found to significantly improve cerebral injuries and behavioral deficits by enhancing Mfn2 expression in wild-type but not CK2α'+/- mice. Taken together, our findings reveal, for the first time, that CK2 is essential for promoting mitochondrial fusion in a Wnt/ß-catenin-dependent manner and suggest that pharmacologically targeting CK2 is a promising therapeutic strategy for ischemic stroke.

6.
BMC Plant Biol ; 20(1): 444, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993508

RESUMO

BACKGROUND: Leaf senescence comprises numerous cooperative events, integrates environmental signals with age-dependent developmental cues, and coordinates the multifaceted deterioration and source-to-sink allocation of nutrients. In crops, leaf senescence has long been regarded as an essential developmental stage for productivity and quality, whereas functional characterization of candidate genes involved in the regulation of leaf senescence has, thus far, been limited in wheat. RESULTS: In this study, we analyzed the expression profiles of 97 WRKY transcription factors (TFs) throughout the progression of leaf senescence in wheat and subsequently isolated a potential regulator of leaf senescence, TaWRKY42-B, for further functional investigation. By phenotypic and physiological analyses in TaWRKY42-B-overexpressing Arabidopsis plants and TaWRKY42-B-silenced wheat plants, we confirmed the positive role of TaWRKY42-B in the initiation of developmental and dark-induced leaf senescence. Furthermore, our results revealed that TaWRKY42-B promotes leaf senescence mainly by interacting with a JA biosynthesis gene, AtLOX3, and its ortholog, TaLOX3, which consequently contributes to the accumulation of JA content. In the present study, we also demonstrated that TaWRKY42-B was functionally conserved with AtWRKY53 in the initiation of age-dependent leaf senescence. CONCLUSION: Our results revealed a novel positive regulator of leaf senescence, TaWRKY42-B, which mediates JA-related leaf senescence via activation of JA biosynthesis and has the potential to be a target gene for molecular breeding in wheat.

7.
J Fish Dis ; 43(12): 1531-1539, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32924173

RESUMO

C-type lectins are carbohydrate-binding proteins that play important roles in immunity by serving as pattern recognition receptors. In the present study, a novel nattectin-like C-type lectin was obtained from the weather loach, Misgurnus anguillicaudatus, designated as MaCTL. MaCTL encodes a peptide with 165 amino acids, with a signal peptide and a single C-type lectin domain (CTLD), containing a galactose-specific QPD motif and a conserved Ca2+ -binding site. Transcripts of MaCTL were significantly upregulated after immune challenge with its pathogen A. hydrophila. In vitro assays with recombinant MaCTL protein revealed that it exhibited hemagglutinating and bacterial agglutinating activities, in a Ca2+ -dependent manner. MaCTL was found to bind to a wide range of bacteria, as well as bind to bacterial polysaccharides LPS and PGN. Moreover, MaCTL displayed antimicrobial activity by inhibiting the growth of bacteria. These results collectively suggest that MaCTL is involved in the antibacterial defence of weather loach.

8.
Chem Commun (Camb) ; 56(80): 12013-12016, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32901620

RESUMO

A palladium-catalyzed arylation/aza-Michael addition cascade reaction of ß-substituted cyclic enones and 2-haloanilines has been reported. Using 1 mol% Pd(PPh3)4 as a catalyst, C2-spiroindolines are accessed via an intermolecular vinylogous arylation of ß-alkyl cyclic enones and 2-haloanilines followed by an intramolecular aza-Michael addition. The functional group tolerance of this transformation is examined by 18 examples in up to 93% yield. In the second part, we developed an α'-arylation/aza-Michael addition cascade strategy to construct azabicyclo[3.2.2]nonanones catalyzed by Pd(MeCN)2Cl2·PPh3. This study provides a quick route to complex and useful spiro- and bridged-heterocycles from readily available starting materials in good yields with high regioselectivity.

9.
Int J Biol Macromol ; 161: 1346-1357, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32784023

RESUMO

In this study, two homogeneous polysaccharides (PFC-1 and PFC-2) having anti-atherosclerotic activity were isolated from Fructus Corni. PFC-1 and PFC-2 were 1,6-α-glucans with the molecular weight of 4.4 kDa and 82.0 kDa, respectively. In the in vitro experiments, PFC-1 and PFC-2 showed significant inhibitory effects on the cholesterol accumulation in RAW264.7 macrophages induced by oxidized low-density lipoproteins (ox-LDL), and the inhibitory rate of PFC-2 was 81.62%. Apolipoprotein E-deficient (ApoE-/-) mice fed high-fat diet (HFD) were used to evaluate the anti-atherosclerotic effects of PFC-2 in vivo. The aortic root lipid area decreased by 55.01% in the PFC-2-administered group as compared to the model group. PFC-2 decreased the levels of serum low-density lipoprotein cholesterol, total cholesterol, triglycerides, and malondialdehyde, increased the superoxide dismutase activity, and reduced the contents of lipid and macrophages in the aortic sinus plaque in ApoE-/- mice fed with HFD. Furthermore, PFC-2 markedly inhibited the expression of type A1 scavenger receptor (SR-A1) and cluster of differentiation 36 (CD36) in ox-LDL-treated macrophages. Taken together, 1,6-α-glucans from Fructus Corni showed significant anti-atherogenic effect, and the mechanism is related to enhanced antioxidant activity of the ApoE-/- mice and down-regulated the expression of SR-A1 and CD36 proteins in macrophages.

10.
Arch Oral Biol ; 117: 104773, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32512259

RESUMO

OBJECTIVE: The aim of this study was to analyze the occurrence and variations in C-shaped canals in ancient Chinese teeth and compare the differences of these features between ancient and age-matched modern populations. DESIGN: Approximately 5000-year-old craniofacial bone remains were collected from the fossils of 38 individuals (total: 68 mandibular second molars) excavated from the Jiaojia site. The control group comprised of an equal number of randomly selected modern samples. We used cone-beam computed tomography to scan the mandible along the apex-crown axis and analyzed the canal morphology, based on Fan's categorization criterion, at 2 mm, 5 mm, and 8 mm to the apical level. Grooves on the lingual and buccal sides were also recorded. RESULTS: The proportion of C-shaped roots among ancient samples on the left and right sides were 48.57 % (17/35 teeth) and 54.55 % (18/33 teeth), respectively, and 51.47 % (35/68 teeth) in the total sample. Conversely, in the control group, 44.12 % (15/34) and 38.24 % (13/34) occurred on the left and right sides, respectively, and 41.18 % (28/68) in the total sample. Among the C-shaped canals from the Jiaojia site samples, the classification type changed between two adjacent levels in 84.31 % of samples. Approximately 35 (51.5 %) teeth had a fused root, 20 (29.41 %) had one shallow buccal and one deep lingual groove. The occurrence of C-shape variation was not significantly correlated with time (p>0.05). CONCLUSIONS: This study identified a high rate of C-shaped root canals among individuals of Jiaojia who lived approximately 5000 years ago.


Assuntos
Cavidade Pulpar , Fósseis , Raiz Dentária , China , Tomografia Computadorizada de Feixe Cônico , Humanos , Mandíbula , Dente Molar
11.
Medicine (Baltimore) ; 99(24): e20253, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541451

RESUMO

This study is to explore the molecular mechanism of benign bile duct hypertrophic scar formation.Differential proteins between the normal fibroblast (NFB) and scar fibroblast (SCFB) were screened by protein chip assay, and analyzed by pathway-enrichment analysis and function-enrichment analysis. The differential proteins were further tested by ELISA. SiRNA-Act B was transfected to SCFB to down-regulate the expression of Act B. NFB was incubated with rh-Act B. The cell apoptosis and cell cycle were determined by flow cytometry. The expression of Act B, Smad2/3, transforming growth factor-ß1 (TGF-ß1), endothelin-1 (ET-1), thrombospondin-1 (Tsp-1), and Oncostatin M (OSM) were detected by Western blot.A total of 37 differential proteins were identified in SCFBs by microarray (P < .05), including 27 up-regulated proteins and 10 down-regulated proteins (P < .05). Their function were associated with Activin signaling, synthesis and degradation of extracellular matrix, formation and activation of cytokine, inflammatory reaction, immunoreaction, tissue damage reaction, cell cycle, migration, apoptosis, and secretion, etc. ELISA results showed that the expression of Act B, TGF-ß1, ET-1 were higher in SCFBs, while the expression of Tsp-1 and OSM were lower in SCFBs (P < .05). After interfered by siRNA-Act B, the expression of Act B mRNA decreased (P < .05). The percentage of early apoptosis increased (P < .05). The expression of Act B, Smad2/3, TGF-ß1 were decreased and Tsp-1, OSM were increased (P < .05). After treatment with rh-Act B, the percentage of G0/G1 phase of NFBs was decreased and that of S phase was increased without significance (P > .05). The expression of Act B, Smad2/3, TGF-ß1 were increased (P < .05) and Tsp-1, OSM were decreased (P < .01).There are differentially expressed proteins between SCFBs and NFBs. Activin B signal plays an important role in the process of NFB transforming to SCFB, and TGF-ß1, Smad2/3, Tsp-1, and OSM are important participants.


Assuntos
Ativinas/metabolismo , Ductos Biliares/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Transdução de Sinais/fisiologia , Adulto , Apoptose/fisiologia , Ciclo Celular/fisiologia , Cicatriz Hipertrófica , Endotelina-1/metabolismo , Matriz Extracelular/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oncostatina M/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Proteína Smad2/metabolismo , Trombospondina 1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
12.
Ann Surg ; 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32502078

RESUMO

OBJECTIVE: To determine the 5-year and temporal performance of TAVR versus SAVR. BACKGROUND: TAVR has become a valuable treatment for severe aortic stenosis but the long-term safety and efficacy remain unclear. METHODS: Databases were searched until October 6, 2019 for randomized trials with ≥5 years' follow-up. Primary outcome was all-cause mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled with random-effects models. RESULTS: We included 4 trials with 3,758 patients. TAVR was associated with a significantly higher 5-year all-cause mortality than SAVR (OR, 1.19; 95% CI, 1.03-1.37; P = 0.02). Landmark analysis showed no significant difference within 2 years (OR, 0.92; 95% CI, 0.79-1.08; P = 0.33) but a statistically higher mortality in TAVR between 2 and 5 years (OR, 1.32; 95% CI, 1.14-1.52; P = 0.0002), with significant difference between these 2 temporal phases (P for interaction = 0.001). Similar interaction was found for cardiovascular mortality and several other outcomes. Rates of all-cause mortality or disabling stroke, permanent pacemaker implantation, aortic-valve rehospitalization, and reintervention were higher, but rates of major bleeding and new-onset fibrillation were lower in TAVR at 5 years. The incidences of myocardial infarction, stroke, and transient ischemic attack were not statistically different between TAVR and SAVR. CONCLUSIONS: TAVR was associated with a significantly higher all-cause mortality at 5 years compared with SAVR. Of note, all-cause mortality presented a characteristic temporal pattern showing increased risk between 2 and 5 years but not within 2 years. Longer-term follow-up data are warranted.

13.
Fish Shellfish Immunol ; 103: 285-292, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32439506

RESUMO

C-type lectins (CTLs) play important roles in innate immune system of crustaceans as pattern recognition receptors (PRRs). In this study, a novel CTL gene was obtained from the red swamp crayfish, Procambarus clarkii, designated as PcLec. PcLec encodes a peptide with 175 amino acids, with a signal peptide and a single carbohydrate recognition domain (CRD). The PcLec transcripts were specifically expressed in crayfish stomach and were induced by bacterial challenge. In vitro assays with recombinant PcLec protein revealed that it had bacterial binding activity, polysaccharide binding activity, bacterial agglutination activity, and antimicrobial activity. Most importantly, PcLec knockdown significantly impaired the survivability of crayfish upon oral infection with its pathogen A. hydrophila. According to these results, we infer that the PcLec plays a crucial role in antibacterial defense of crayfish.

14.
Fish Shellfish Immunol ; 103: 277-284, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32439510

RESUMO

Whey acidic protein domain (WAPD) occurs in a variety of proteins in animals and many of WAPD-containing proteins are involved in immunity. In the present study, a novel protein containing three WAPDs was identified from the weather loach, Misgurnus anguillicaudatus, designated as MaTWD. MaTWD share high identity with TWDs from fish but low identity with TWDs from other animal phyla. MaTWD transcripts mainly distributed in gills and head kidney responded to bacterial challenge with significant upregulation. In vitro assay with recombinant MaTWD protein revealed that MaTWD had antiprotease activity against bacterial proteases. Moreover, MaTWD exhibited bacterial binding capacity and antimicrobial activity. Most importantly, exogenous MaTWD protected loach against bacterial infection by reducing loach mortality. We infer that MaTWD participates in the antibacterial immunity of loach via its antiprotease and antimicrobial activities.

15.
J Am Chem Soc ; 142(16): 7328-7333, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32255625

RESUMO

Chiral nitriles are valuable molecules in modern organic synthesis and drug discovery. Selectively differentiating the two nitrile groups of widely available malononitrile derivatives is a straightforward yet underdeveloped route to construct enantioenriched nitriles. Here we report an enantioselective nickel-catalyzed desymmetrization of malononitriles for the generation of nitrile-containing all-carbon quaternary stereocenters. This protocol involves a nickel-catalyzed addition of aryl boronic acids to alkynes, followed by a selective nitrile insertion, providing unprecedented access to enantioenriched 5-7-membered α-cyano-cycloenones with a fully substituted olefin from a broad range of substrates. The synthetic utility of these nitrile products is demonstrated by gram-scale synthesis and conversion to several useful functional groups.

16.
ChemSusChem ; 13(10): 2769-2778, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32112521

RESUMO

The photocatalytic reduction of N2 to NH3 is considered a promising strategy to alleviate human need for accessible nitrogen and environmental pollution, for which developing a photocatalyst is an effective method to complete the transformation of this process. We firstly design a series of highly efficient and stable polyoxometalates (POMs)-based zeolitic imidazolate framework-67 (ZIF-67) photocatalysts for N2 reduction. ZIF-67 can effectively fix N2 owing to its porosity. Integration of POMs cluster contributes enormous advantages in terms of broadening the absorption spectrum to improve sunlight utilization, enhance the stability of the materials, effectively inhibit the recombination of photo-generated electron-hole pairs, and reduce charge-transfer impedance. POMs can absorb light to convert into reduced POMs, which have stronger reducing ability to provide ample electrons to reduce N2 . The reduced POMs can recover their oxidation state through contact with an oxidant, which forms a self-recoverable and recyclable photocatalytic fixing N2 system. The photocatalytic activity enhances with the increasing number V substitutions in the POMs. Satisfactorily, ZIF-67@K11 [PMo4 V8 O40 ] (PMo4 V8 ) displays the most significant photocatalytic N2 activity with a NH3 yield of 149.0 µmol L-1 h-1 , which is improved by 83.5 % (ZIF-67) and 78.9 % (PMo4 V8 ). The introduction of POMs provides new insights for the design of high-performance photocatalyst nanomaterials to reduce N2 .

17.
Biochem Pharmacol ; 177: 113932, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32222456

RESUMO

Histone post-translational modifications (PTMs) have been shown to be highly associated with inflammation response, suggesting a therapeutic significance of pharmacologically editing histone PTMs. Currently reported anti-inflammation small-molecules mainly target histone PTMs writers or erasers for methylation, phosphorylation, and acetylation. Although histone chaperones also appear to be involved in inflammation signaling cascades, whether small-molecules could target histone chaperones to show anti-inflammation effects has still been rarely discovered. In this study, natural product artone was found to show obvious inhibitory effects on microglia-mediated neuroinflammation by directly targeting ASF1a, which is a histone-remodeling chaperone. Mechanism study revealed that artone modulated histone H3 PTMs profile by down-regulating acetylation and trimethylation modification levels at sites K4, K9, K18 and K27. Artone-dependent regulations on PTMs further caused an effective inhibition on transcription factor NF-κB assembling to promoters of pro-inflammatory cytokine genes including Tnf-α, Il-6 and Rgs3, indicating a distinctive anti-neuroinflammation mechanism. Collectively, we reported artone as the first small-molecule targeting histone-remodeling chaperone ASF1a for anti-neuroinflammation. Moreover, these findings broaden our knowledge of histone chaperone as a druggable target protein for neuroinflammation inhibition, and open a new avenue to novel therapy strategy for inflammation-associated neurological disorders.

18.
J Environ Radioact ; 217: 106202, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32063554

RESUMO

Uranium mining and milling activities for many years resulted in release of uranium into the adjoining soil in varying degrees. Bioremediation approaches (i.e., immobilization via the action of bacteria) resulting in uranium bearing solid is supposed as an economic and clean in-situ approach for the treatment of uranium contaminated sites. This study purposes to determine the immobilization efficiency of uranium in soil by Leifsonia sp. The results demonstrated that cells have a good proliferation ability under the stress of uranium and play a role in retaining uranium in soil. Residual uranium in active Leifsonia-medium group (66%) was higher than that in the controls, which was 31% in the deionised water control, 46% in the Leifsonia group, and 47% in the medium group, respectively. This indicated that Leifsonia sp. facilitates the immobilization efficiency of uranium in soil by converting part of the reducible and oxidizable fraction of uranium into the residual fraction. X-ray photoelectron fitting results showed that tetravalent states uranium existed in the soil samples, which indicated that the hexavalent uranium was converted into tetravalent by cells. This is the first report of effect of Leifsonia sp. on uranium immobilization in soil. The findings implied that Leifsonia sp. could, to some extent, prevent the migration and diffusion of uranium in soil by changing the chemical states into less toxicity and less risky forms.


Assuntos
Monitoramento de Radiação , Solo , Mineração , Poluentes do Solo , Urânio
19.
Theranostics ; 10(2): 797-815, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903151

RESUMO

Background: Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional activation, chromosome packaging, and DNA repair. Previous studies mainly focused on PTMs by directly targeting histone-modifying enzymes such as HDACs and HATs. Methods and Results: In this study, we discovered a previously unexplored regulation mechanism for histone PTMs by targeting transcription regulation factor 14-3-3ζ. Mechanistic studies revealed 14-3-3ζ dimerization as a key prerequisite, which could be dynamically induced via an allosteric effect. The selective inhibition of 14-3-3ζ dimer interaction with histone H3 modulated histone H3 PTMs by exposing specific modification sites including acetylation, trimethylation, and phosphorylation, and reprogrammed gene transcription profiles for autophagy-lysosome function and endoplasmic reticulum stress. Conclusion: Our findings demonstrate the feasibility of editing histone PTM patterns by targeting transcription regulation factor 14-3-3ζ, and provide a distinctive PTM editing strategy which differs from current histone modification approaches.

20.
Int J Mol Sci ; 21(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941000

RESUMO

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It involves progressive impairment of cognitive function. A growing number of neuroprotective compounds have been identified with potential anti-AD properties through in vitro and in vivo models of AD. Quercetin, a natural flavonoid contained in a wide range of plant species, is repeatedly reported to exert neuroprotective effects in experimental animal AD models. However, a systematic analysis of methodological rigor and the comparison between different studies is still lacking. A systematic review uses a methodical approach to minimize the bias in each independent study, providing a less biased, comprehensive understanding of research findings and an objective judgement of the strength of evidence and the reliability of conclusions. In this review, we identified 14 studies describing the therapeutic efficacy of quercetin on animal AD models by electronic and manual retrieval. Some of the results of the studies included were meta-analyzed by forest plot, and the methodological quality of each preclinical trial was assessed with SYRCLE's risk of bias tool. Our results demonstrated the consistent neuroprotective effects of quercetin on different AD models, and the pharmacological mechanisms of quercetin on AD models are summarized. This information eliminated the bias of each individual study, providing guidance for future tests and supporting evidence for further implementation of quercetin into clinical trials. However, the limitations of some studies, such as the absence of sample size calculations and low method quality, should also be noted.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Quercetina , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Humanos , Fármacos Neuroprotetores/farmacocinética , Fármacos Neuroprotetores/uso terapêutico , Quercetina/farmacocinética , Quercetina/uso terapêutico
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