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1.
Int J Biol Macromol ; 188: 595-608, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34389388

RESUMO

Phosphate transporters (PHTs) mediate the uptake and translocation of phosphate in plants. A comprehensive analysis of the PHT family in aquatic plant is still lacking. In this study, we identified 73 PHT members of six major PHT families from four duckweed species. The phylogenetic analysis, gene structure and protein characteristics analysis revealed that PHT genes are highly conserved among duckweeds. Interaction network and miRNA target prediction showed that SpPHTs could interact with the important components of the nitrate/phosphate signaling pathway, and spo-miR399 might be a central regulator that mediates phosphate signal network in giant duckweed (Spirodela polyrhiza). The modeled 3D structure of SpPHT proteins shared a high level of homology with template structures, which provide information to understand their functions at proteomic level. The expression profiles derived from transcriptome data and quantitative real-time PCR revealed that SpPHT genes are respond to exogenous stimuli and remarkably induced by phosphate starvation, phosphate is absorbed from aquatic environment by the whole duckweed plant. This study lays the foundation for further functional studies on PHT genes for genetic improvement and the promotion of phosphate uptake efficiency in duckweeds.

2.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203933

RESUMO

Natural resistance-associated macrophage proteins (Nramps) are specific metal transporters in plants with different functions among various species. The evolutionary and functional information of the Nramp gene family in Spirodela polyrhiza has not been previously reported in detail. To identify the Nramp genes in S. polyrhiza, we performed genome-wide identification, characterization, classification, and cis-elements analysis among 22 species with 138 amino acid sequences. We also conducted chromosomal localization and analyzed the synteny relationship, promoter, subcellular localization, and expression patterns in S. polyrhiza. ß-Glucuronidase staining indicated that SpNramp1 and SpNramp3 mainly accumulated in the root and joint between mother and daughter frond. Moreover, SpNramp1 was also widely displayed in the frond. SpNramp2 was intensively distributed in the root and frond. Quantitative real-time PCR results proved that the SpNramp gene expression level was influenced by Cd stress, especially in response to Fe or Mn deficiency. The study provides detailed information on the SpNramp gene family and their distribution and expression, laying a beneficial foundation for functional research.


Assuntos
Araceae/genética , Cádmio/toxicidade , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Família Multigênica , Proteínas de Plantas/genética , Estresse Fisiológico/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Araceae/efeitos dos fármacos , Proteínas de Transporte de Cátions/química , Proteínas de Transporte de Cátions/metabolismo , Cromossomos de Plantas/genética , Sequência Conservada , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Estresse Fisiológico/efeitos dos fármacos , Sintenia/genética
3.
J Ethnopharmacol ; 278: 114280, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34082014

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gross Saponins of Tribulus terrestris L. Fruit (GSTTF) has been reported to have a protective effect against ischemic stroke, but the related mechanism is complex and still not fully investigated. AIM OF THE STUDY: The combination of metabolomics and proteomics approach was applied to reveal the mechanisms of GSTTF in treating ischemic stroke. MATERIALS AND METHODS: The metabolite and protein changes in brain tissue were analyzed by the LC-MS-based untargeted metabolomics method and tandem mass tags (TMT)-based quantitative proteomics technology. The multivariate statistical analysis and protein-protein interaction (PPI) analysis were conducted to screen out the biomarkers, and their related pathway was further investigated by the joint pathway analysis. RESULTS: A total of 110 metabolites and 359 differential proteins, which were mainly associated with complement and coagulation cascades, sphingolipid metabolism, glycerophospholipid metabolism, glutathione metabolism, and platelet activation, etc. were screened out from the rat brain tissue. The PPI network exhibited that the protein F2, Fga, Fgb, Fgg, Plg, and C3, which are greatly involved in the complement and coagulation cascades, have a relatively high connectivity degree, indicating their importance in the process of middle cerebral artery occlusion (MCAO). The GSTTF exerted a protective effect against MCAO via modulating multiple proteins on this pathway. Moreover, F2 played a key role during the protective process and worth to be further investigated due to it has been reported as one of the therapeutic targets of ischemic stroke. CONCLUSION: The present study could improve the understanding of the potential therapeutic mechanism of GSTTF against ischemic stroke.

4.
Biomed Res Int ; 2021: 6649085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136571

RESUMO

Aging affects the brain function in elderly individuals, and Dushen Tang (DST) is widely used for the treatment of senile diseases. In this study, the protective effect of DST against memory impairment was evaluated through the Morris water maze (MWM) test and transmission electron microscopy (TEM). A joint analysis was also performed using LC-MS metabolomics and the microbiome. The MWM test showed that DST could significantly improve the spatial memory and learning abilities of rats with memory impairment, and the TEM analysis showed that DST could reduce neuronal damage in the hippocampus of rats with memory impairment. Ten potential biomarkers involving pyruvate metabolism, the synthesis and degradation of ketone bodies, and other metabolic pathways were identified by the metabolomic analysis, and it was found that 3-hydroxybutyric acid and lactic acid were involved in the activation of cAMP signaling pathways. The 16S rDNA sequencing results showed that DST could regulate the structure of the gut microbiota in rats with memory impairment, and these effects were manifested as changes in energy metabolism. These findings suggest that DST exerts a good therapeutic effect on rats with memory impairment and that this effect might be mainly achieved by improving energy metabolism. These findings might lead to the potential development of DST as a drug for the treatment of rats with memory impairment.


Assuntos
Encéfalo/efeitos dos fármacos , Galactose/química , Metabolômica , Microbiota/efeitos dos fármacos , Panax/química , Ácido 3-Hidroxibutírico/química , Animais , Biomarcadores/metabolismo , Cromatografia em Camada Delgada , AMP Cíclico/metabolismo , DNA Ribossômico/metabolismo , Metabolismo Energético , Hipocampo/efeitos dos fármacos , Ácido Láctico/química , Masculino , Aprendizagem em Labirinto , Memória , Microscopia Eletrônica de Transmissão , Modelos Animais , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
5.
Genomics ; 113(4): 1761-1777, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33862182

RESUMO

WRKY is one of the largest transcription factor families across higher plant species and is involved in important biological processes and plant responses to various biotic/abiotic stresses. However, only a few investigations on WRKYs have been conducted in aquatic plants. This study first systematically analyzed the gene structure, protein properties, and phylogenetic relationship of 693 WRKYs in nine aquatic and two wetland plants at the genome-wide level. The pattern of WRKY groups in two aquatic ferns provided new evidence for the origin and evolution of WRKY genes. ARE cis-regulatory elements show an unusual high frequency in the promoter region of WRKY genes, indicating the adaptation to the aquatic habitat in aquatic plants. The WRKY gene family experienced a series of gene loss events in aquatic plants, especially group III. Further studies were conducted on the interaction network of SpWRKYs, their target genes, and non-coding RNAs. The expression profile of SpWRKYs under phosphate starvation, cold, and submergence conditions revealed that most SpWRKYs are involved in the response to abiotic stresses. Our investigations lay the foundation for further study on the mechanism of WRKYs responding to abiotic stresses in aquatic plants.

6.
Elife ; 102021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33683200

RESUMO

TRPC5 channel is a nonselective cation channel that participates in diverse physiological processes. TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression, and kidney disease. However, the binding sites and inhibitory mechanism of TRPC5 inhibitors remain elusive. Here, we present the cryo-EM structures of human TRPC5 in complex with two distinct inhibitors, namely clemizole and HC-070, to the resolution of 2.7 Å. The structures reveal that clemizole binds inside the voltage sensor-like domain of each subunit. In contrast, HC-070 is wedged between adjacent subunits and replaces the glycerol group of a putative diacylglycerol molecule near the extracellular side. Moreover, we found mutations in the inhibitor binding pockets altered the potency of inhibitors. These structures suggest that both clemizole and HC-070 exert the inhibitory functions by stabilizing the ion channel in a nonconductive closed state. These results pave the way for further design and optimization of inhibitors targeting human TRPC5.

7.
Semin Cell Dev Biol ; 114: 126-133, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33583737

RESUMO

Emerging evidence has shown that several SOX family transcription factors are key regulators of stem/progenitor cell fates in the mammary gland. These cell-fate regulators are often upregulated in breast cancer and contribute to tumor initiation and progression. They induce lineage plasticity and the epithelial-mesenchymal transition, which promotes tumor invasion, metastasis, and therapeutic resistance. SOX factors act through modulating multiple oncogenic signaling pathways in breast cancer. In addition to the cell-autonomous functions, new evidence suggests they can shape the tumor immune microenvironment. Here, we will review the molecular and functional evidence linking SOX factors with mammary gland development and discuss how these cell-fate regulators are co-opted in breast cancer.

8.
Ophthalmic Plast Reconstr Surg ; 37(1): 27-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32282646

RESUMO

PURPOSE: To prospectively explore the incidence and risk factors of moderate to severe pain after primary and secondary orbital implantation following evisceration or enucleation surgery. METHODS: One hundred eighteen patients under general anesthesia for orbital implantation were enrolled in this study. In 91 patients, primary orbital implantation followed evisceration, and in 27 patients, the implantation was secondary after previous evisceration or enucleation surgery. Medical interventions for all participants were followed by standardized surgical, anesthetic, and analgesic protocols. Postoperative pain (POP) intensity was quantified by an 11-point numerical rating scale within 72 hours after the surgery, numerical rating scale ≥4 was considered moderate to severe POP. Multivariate logistic regression was utilized to identify the risk factors related to the development of POP. RESULTS: Thirty-five patients (29.7%) displayed moderate to severe POP, particularly within 6 to 24 hours after surgery, which peaked at 24 hours. Of these patients, 26 patients who were unable to tolerate the pain received additional doses of analgesics during in-hospital stay. Logistic regression model revealed that preoperative anxiety (odds ratios = 4.890; p = 0.002), congenital microphthalmia (odds ratios = 14.602; p = 0.038), and surgical time longer than 60 minutes (odds ratios = 5.586; p = 0.001) were significantly associated with moderate to severe POP after orbital implantation. CONCLUSIONS: Orbital implantation after evisceration or enucleation surgery is likely to cause moderate to severe pain intensity in the early postoperative period. Preoperative anxiety, prolonged surgical time, and congenital microphthalmia were the risk factors.


Assuntos
Implantes Orbitários , Enucleação Ocular , Evisceração do Olho , Humanos , Incidência , Implantes Orbitários/efeitos adversos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Estudos Retrospectivos , Fatores de Risco
9.
J Mol Cell Cardiol ; 152: 52-68, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33301800

RESUMO

Pathological cardiac remodeling, characterized by excessive deposition of extracellular matrix proteins and cardiac hypertrophy, leads to the development of heart failure. Meprin α (Mep1a), a zinc metalloprotease, previously reported to participate in the regulation of inflammatory response and fibrosis, may also contribute to cardiac remodeling, although whether and how it participates in this process remains unknown. Here, in this work, we investigated the role of Mep1a in pathological cardiac remodeling, as well as the effects of the Mep1a inhibitor actinonin on cardiac remodeling-associated phenotypes. We found that Mep1a deficiency or chemical inhibition both significantly alleviated TAC- and Ang II-induced cardiac remodeling and dysfunction. Mep1a deletion and blocking both attenuated TAC- and Ang II-induced heart enlargement and increases in the thickness of the left ventricle anterior and posterior walls, and reduced expression of pro-hypertrophic markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and myosin heavy chain beta (ß-MHC). In addition, Mep1a deletion and blocking significantly inhibited TAC- and Ang II-induced cardiac fibroblast activation and production of extracellular matrix (ECM). Moreover, in Mep1a-/- mice and treatment with actinonin significantly reduced Ang II-induced infiltration of macrophages and proinflammatory cytokines. Notably, we found that in vitro, Mep1a is expressed in cardiac myocytes and fibroblasts and that Mep1a deletion or chemical inhibition both markedly suppressed Ang II-induced hypertrophy of rat or mouse cardiac myocytes and activation of rat or mouse cardiac fibroblasts. In addition, blocking Mep1a in macrophages reduced Ang II-induced expression of interleukin (IL)-6 and IL-1ß, strongly suggesting that Mep1a participates in cardiac remodeling processes through regulation of inflammatory cytokine expression. Mechanism studies revealed that Mep1a mediated ERK1/2 activation in cardiac myocytes, fibroblasts and macrophages and contributed to cardiac remodeling. In light of our findings that blocking Mep1a can ameliorate cardiac remodeling via inhibition of cardiac hypertrophy, fibrosis, and inflammation, Mep1a may therefore serve as a strong potential candidate for therapeutic targeting to prevent cardiac remodeling.

10.
Int J Clin Exp Pathol ; 13(11): 2720-2726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33284867

RESUMO

Ulinastatin (UTI) is a trypsin inhibitor observed in urine. UTI can treat some diseases by inhibiting the broad-spectrum hydrolysis activity of various enzymes and other pharmacological effects. UTI can widely treat pancreatitis, systemic multiple organ dysfunction syndrome, circulatory failure, and toxic shock clinically. The liver is a major metabolic organ of the human body. Various biological metabolic reactions require the liver's participation. When various physical and chemical factors drive the body, it will damage the liver to varying degrees. As a clinically effective drug, UTI is also known to treat some liver diseases. This article mainly describes UTI's research progress in treating septic liver injury, hepatitis, liver fibrosis, autoimmune liver disease with liver failure, and liver ischemia-reperfusion injury.

11.
Clin Invest Med ; 43(4): E44-55, 2020 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-33370524

RESUMO

PURPOSE: The purpose of this study was to determine whether ticagrelor, a classic anti-platelet drug, has a therapeutic effect on sepsis-induced myocardial injury. METHODS: The C57BL6J mice received oral ticagrelor (10, 25 and 50 mg/kg) for seven days after which cecum ligation and puncture (CLP) were performed. An adenosine-receptor antagonist (CGS15943) was administered two hours before CLP. After 24 h, cardiac function was measured using cardiac echocardiography, then the heart and blood were collected. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL staining) were used to observe pathological changes and cardiomyocyte apoptosis. Plasma concentration of TNF-α, IL-6 and adenosine and myocardial tissue levels of TNF-α and IL-6 were determined. Survival analysis was performed. Western blot was used to determine the expression of a signalling protein in the myocardial tissue. RESULTS: The HE and TUNEL staining showed less inflammatory cell infiltration and less cardiomyocyte apoptosis in the ticagrelor group. Cardiac echocardiography showed preserved heart function in the ticagrelor group. Plasma TNF-α, IL-6 and relative expression of TNF-α and IL-6 in myocardial tissue were significantly lower in the ticagrelor group. Plasma adenosine levels were significantly higher in the ticagrelor group. Adenosine-receptor antagonists significantly blocked the protective effect of ticagrelor. Ticagrelor reduced the mortality of sepsis mice, and this reduction was blocked by the adenosine-receptor antagonist. Western blot showed that ticagrelor activated the phosphorylation of AKT and mTOR. Adenosine-receptor antagonists inhibited the activation of AKT and mTOR. CONCLUSION: The protective effect of ticagrelor was dependent on adenosine-receptor activation, with downstream upregulation of phosphorylation of AKT and mTOR.

12.
Bioresour Technol ; 317: 124029, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32916457

RESUMO

Duckweed is a potential biomass source for alternative energy production. This work reports the effects of trophic modes on growth rates, biomass accumulation, and removal rates of pollutant by duckweed. Glucose, fructose, galactose, sucrose, and maltose all supported heterotrophic and mixotrophic growth of duckweed. The mixotrophic growth rate was 4.98 and 6.22 times higher than those in heterotrophic and photoautotrophic conditions, respectively. Notably, mixotrophy produced more biomass than the simple sum of the biomass accumulation during heterotrophy and photoautotrophy. Mixotrophy was also superior in starch and protein production, as well as in removal rates of nutrients and organic carbon from the growth medium. However, the starch content of duckweed grown heterotrophically was 2.06 times higher than in mixotrophy, suggesting a combination of mixotrophy and heterotrophy as an effective strategy for starch-rich biomass production. This study thus provides a paradigm for future studies supporting duckweed-based biomass production and organic wastewater treatment.


Assuntos
Araceae , Poluentes Ambientais , Biomassa , Carbono , Processos Heterotróficos
13.
J Ethnopharmacol ; 263: 113202, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-32768639

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tribulus terrestris L. belongs to the family Zygophyllaceae and has been widely used as a folk medicine for a long history in Asian countries. Gross saponins of Tribulus terrestris L. fruit (GSTTF) has an obvious neuroprotective effect on the treatment of ischemic stroke, but its potential therapeutic mechanisms have not been thoroughly studied. AIM OF THE STUDY: To investigate the protective effect of GSTTF against ischemic stroke in rat. MATERIALS AND METHODS: The combination of metabolomics and network pharmacology analysis was applied to investigate the protective effects of GSTTF on ischemic stroke and its putative mechanism. The related pathway of the biomarkers highlighted from metabolomics analysis was explored, then the possible targets of GSTTF were further revealed by network pharmacology analysis. Molecular docking was conducted to investigate the interaction between the active compound and target protein. RESULTS: Metabolomics analysis showed that metabolic disturbances were observed in serum for the rats in middle cerebral artery occlusion (MCAO). These MCAO-induced deviations in serum metabolism can be reversely changed by GSTTF via metabolic pathways regulation. Twenty-four proteins with the connectivity degree larger than 15 were selected by the network pharmacology analysis, which are considered as the possible therapeutic targets of the GSTTF against ischemic stroke. The results of molecular docking showed that the active compounds were capable of binding to the representative potential targets HSD11B1 and AR, respectively. And the docking mode of two compounds with the lowest binding energy to their target protein was illustrated by the ribbon binding map. CONCLUSION: The present study combines metabolomics and network pharmacology analysis to investigate the mechanism of MCAO-induced ischemic stroke and reveal the efficiency and possible mechanisms of GSTTF for ischemic stroke. Further studies on the bioactive saponin as well as their synergistic action on ischemic stroke will be conducted to better reveal the underlying mechanisms.


Assuntos
Frutas , AVC Isquêmico/prevenção & controle , Metabolômica/métodos , Fármacos Neuroprotetores/uso terapêutico , Saponinas/uso terapêutico , Tribulus , Animais , AVC Isquêmico/metabolismo , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/fisiologia , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/metabolismo , Estrutura Secundária de Proteína , Ratos , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Saponinas/metabolismo
14.
Int J Burns Trauma ; 10(3): 47-54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714627

RESUMO

OBJECTIVE: To explore the effects of sleep deprivation on perioperative general anesthesia in rats. METHODS: 45 healthy male Sprague-Dawley (SD) rats were randomly divided into 3 groups, the control group (Group A), the anesthesia group (Group B) and the sleep deprivation anesthesia group (Group C), 15 in each group. The sleep deprivation model was established by improving multi-platform water environment method. The group B and C were received propofol 80 mg/kg by intraperitoneally, the group A was given the same dose of normal saline. The EEG in each group was measured. The GABAa R-ß3 protein in cerebral cortex was detected by Western Blot. The rats were treated with Brennan incision, and the changes of thermal pain sensitive (PWL) and open field behavior were measured in each group. RESULTS: In group C, the δ band of brainwave of EEG increased significantly, the disappearance time of righting reflex shortened significantly, the recovery time prolonged significantly, the GABAa R-ß3 protein was significantly increased, and the time of passing through the central area before operation was significantly decreased. CONCLUSION: Sleep deprivation can significantly inhibit the electrical activity of rat cerebral cortex induced by propofol, up-regulating the GABAa R-ß3 protein in cortex.

15.
Cell Rep ; 31(10): 107742, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32521267

RESUMO

Lineage plasticity is important for the development of basal-like breast cancer (BLBC), an aggressive cancer subtype. While BLBC is likely to originate from luminal progenitor cells, it acquires substantial basal cell features and contains a heterogenous collection of cells exhibiting basal, luminal, and hybrid phenotypes. Why luminal progenitors are prone to BLBC transformation and what drives luminal-to-basal reprogramming remain unclear. Here, we show that the transcription factor SOX9 acts as a determinant for estrogen-receptor-negative (ER-) luminal stem/progenitor cells (LSPCs). SOX9 controls LSPC activity in part by activating both canonical and non-canonical nuclear factor κB (NF-κB) signaling. Inactivation of TP53 and RB via expression of SV40 TAg in a BLBC mouse tumor model leads to upregulation of SOX9, which drives luminal-to-basal reprogramming in vivo. Furthermore, SOX9 deletion inhibits the progression of ductal carcinoma in situ (DCIS)-like lesions to invasive carcinoma. These data show that ER- LSPC determinant SOX9 acts as a lineage plasticity driver for BLBC progression.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição SOX9/metabolismo , Animais , Linhagem da Célula , Plasticidade Celular/fisiologia , Proliferação de Células/fisiologia , Progressão da Doença , Feminino , Humanos , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regulação para Cima
16.
J Pain Res ; 13: 947-953, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32440200

RESUMO

Purpose: The aim of this study was to evaluate postoperative discomfort in patients undergoing ambulatory strabismus under general anesthesia, and to identify risk factors associated with the discomfort. Patients and Methods: A cross-sectional study was conducted among 210 consecutive patients undergoing ambulatory strabismus under general anesthesia. Postoperative discomfort including nausea, vomiting, dizziness, and headache was recorded and quantified. Univariable and multivariable logistic regression were performed to detect the risk factors associated with postoperative discomfort. Results: Of 210 participants, 199 (94.76%) patients experienced mild discomfort after ambulatory strabismus surgery under general anesthesia, and 31 (14.76%), 11 (5.24%), 60 (28.57%), 23 (10.95%) patients suffered from nausea, vomiting, dizziness, and headache, respectively. A multivariate analysis indicated that female sex, the surgery on inferior rectus, and the surgery on inferior oblique were the independent risk factors for postoperative vomiting while, mild anxiety was the independent risk factor for postoperative dizziness. Conclusion: Patients undergoing ambulatory strabismus surgery tended to experience postoperative nausea and dizziness. Female sex, the surgery on inferior rectus, mild anxiety, and the surgery on inferior oblique were the independent predictors of postoperative discomfort.

17.
Dev Cell ; 53(5): 503-513.e5, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32413329

RESUMO

Bone marrow (BM) mesenchymal stem and progenitor cells (MSPCs) are a critical constituent of the hematopoietic stem cell (HSC) niche. Previous studies have suggested that the zinc-finger epithelial-mesenchymal transition transcription factor Snai2 (also known as Slug) regulated HSCs autonomously. Here, we show that Snai2 expression in the BM is restricted to the BM stromal compartment where it regulates the HSC niche. Germline or MSPC-selective Snai2 deletion reduces the functional MSPC pool and their mesenchymal lineage output and impairs HSC niche function during homeostasis and after stress. RNA sequencing analysis revealed that Spp1 (osteopontin) expression is markedly upregulated in Snai2-deficient MSPCs. Genetic deletion of Spp1 in Snai2-deficient mice rescues MSPCs' functions. Thus, SNAI2 is a critical regulator of the transcriptional network maintaining MSPCs by the suppression of osteopontin expression.


Assuntos
Células da Medula Óssea/metabolismo , Osteopontina/genética , Fatores de Transcrição da Família Snail/metabolismo , Nicho de Células-Tronco , Animais , Células da Medula Óssea/citologia , Células Cultivadas , Deleção de Genes , Camundongos , Camundongos Endogâmicos C57BL , Osteopontina/metabolismo , Fatores de Transcrição da Família Snail/genética
18.
Br J Pharmacol ; 177(12): 2872-2885, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32072633

RESUMO

BACKGROUND AND PURPOSE: Abdominal aorticaneurysm (AAA) rupture is mainly due to elastic lamina degradation. As a metalloendopeptidase, meprin-α (Mep1A) critically modulates the activity of proteins and inflammatory cytokines in various diseases. Here, we sought to investigate the functional role of Mep1A in AAA formation and rupture. EXPERIMENTAL APPROACH: AAA tissues were detected by using real-time PCR (RT-PCR), western blotting (WB), and immunohistochemistry. Further mechanistic studies used RT-PCR, WB, and enzyme-linked immunosorbent assays. KEY RESULTS: Mep1A mediated AAA formation by regulating the mast cell (MC) secretion of TNF-α, which promoted matrix metalloproteinase (MMP) expression and apoptosis in smooth muscle cells (SMCs). Importantly, increased Mep1A expression was found in human AAA tissues and in angiotensin II-induced mouse AAA tissues. Mep1A deficiency reduced AAA formation and increased the survival rate of AAA mice. Pathological analysis showed that Mep1A deletion decreased elastic lamina degradation and SMC apoptosis in AAA tissues. Furthermore, Mep1A was expressed mainly in MCs, wherein it mediated TNF-α expression. Mep1A inhibitor actinonin significantly inhibited TNF-α secretion in MCs. TNF-α secreted by MCs enhanced MMP2 expression in SMCs and promoted SMC apoptosis. CONCLUSION AND IMPLICATIONS: Taken together, these data suggest that Mep1A may be vital in AAA pathophysiology by regulating TNF-α production by MCs. Knocking out Mep1A significantly decreased AAA diameter and improved AAA stability in mice. Therefore, Mep1A is a potential new therapeutic target in the development of AAA.


Assuntos
Aneurisma da Aorta Abdominal , Animais , Mastócitos , Metaloproteinase 2 da Matriz , Camundongos , Tiopronina , Fator de Necrose Tumoral alfa
19.
Nanoscale ; 12(2): 983-990, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31840705

RESUMO

Sustainable production of hydrogen by water splitting requires the exploration of highly efficient electrocatalysts from abundant non-precious metals on Earth. Ni(OH)2 hollow nanorod arrays were obtained on Ni foam by simple alkali etching, and FeOOH was electrodeposited on the walls of hollow nanorods to construct FeOOH@Ni(OH)2 sandwich hollow nanorod arrays, which help overcome the drawbacks of the poor conductivity and poor stability of FeOOH and boost the catalytic performance of the oxygen evolution reaction (OER) in comparison with the individual components. A fully contacted three-dimensional nanorod array structure provides many exposed catalytically active sites and promotes charge transfer during the electrochemical OER process. The presence of FeOOH can promote the formation of a more conductive catalytically active component, NiOOH, which improves the catalytic performance of Ni(OH)2. The electronic interaction and synergistic catalysis between nickel and iron enhances the electrochemical performance of the catalyst significantly. The optimized FeOOH@Ni(OH)2 sandwich hollow nanorod arrays show an outstanding OER activity with a small overpotential of 245 mV at 50 mA cm-2 and a low Tafel slope of 45 mV dec-1. The catalyst can maintain a substantially constant voltage over 40 h in 1.0 M KOH solution. Our work provides a new strategy to prepare Ni-Fe bimetallic materials as OER electrocatalysts.

20.
Metabolites ; 9(10)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640179

RESUMO

Stroke is one of the leading causes of death and long-term disability worldwide. Gross saponins of Tribulus terrestris fruit (GSTTF) has been used for neuroprotective therapy on convalescents of ischemic stroke. But the related therapeutic mechanisms have not yet been well investigated. This study aimed to investigate the protective effects of GSTTF on ischemic stroke using metabolomics coupled with network pharmacology analysis. The rat urine sample was collected and profiled by an LC-MS-based metabolomics approach. The pathway analysis was performed based on the highlighted biomarkers, then the network pharmacology approach was applied to screen the potential therapeutic targets of GSTTF. Metabolomics analysis showed that a series of metabolic perturbations occurred in the middle cerebral artery occlusion (MCAO) group compared with the sham group. Gross saponins of Tribulus terrestris fruit can change the MCAO-induced urine metabolic deviations in a reverse manner via regulating multiple metabolic pathways. Two proteins, inducible nitric oxide synthase (NOS2) and glycogen synthase kinase-3 beta (GSK3B), were highlighted by the network pharmacology analysis, which may be the potential therapeutic targets for the GSTTF against ischemic stroke. This study provides an overview of the mechanism of MCAO-induced ischemic stroke and investigates the efficacy of GSTTF in the treatment of ischemic stroke. Further study is needed to reveal its underlying mechanisms more clearly.

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