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1.
Zhongguo Zhong Yao Za Zhi ; 47(9): 2547-2555, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35531703

RESUMO

This Meta-analysis was designed to evaluate the effects of Bailing Capsules on microinflammation and nutritional status of maintenance hemodialysis patients, and to determine its efficacy and safety. The randomized controlled trials concerning the intervention of microinflammation and nutritional status in maintenance hemodialysis patients with Bailing Capsules were searched from Chinese and English databases including CNKI, Wanfang, VIP, PubMed, EMbase, and Cochrane Library. A total of 16 articles were obtained, involving 1 095 cases. As revealed by Meta-analysis,(1)Bailing Capsules lowered the levels of serum high sensitivity C-reactive protein(SMD=-0.92, 95%CI[-1.05,-0.80], P<0.000 01), interleukin-6(SMD=-1.49, 95%CI[-1.96,-1.02], P<0.000 01), and tumor necrosis factor-α(SMD=-1.48, 95%CI[-1.68,-1.28], P<0.000 01) in patients with maintenance hemodialysis, thus alleviating microinflammation.(2)Bailing Capsules elevated the levels of serum hemoglobin(SMD=1.37, 95%CI[1.21, 1.54], P<0.000 01), albumin(SMD=0.78, 95%CI[0.57, 0.98], P<0.000 01), and triglyceride(SMD=0.29, 95%CI[0.07, 0.50], P=0.01) in patients with hemodialysis to improve their nutritional status.(3)Bailing Capsules reduced the incidence of cardiovascular events(RR=0.45, 95%CI[0.34, 0.59], P<0.000 01).(4)A total of six patients presented with mild gastrointestinal discomfort after receiving Bailing Capsules, and no serious adverse reactions were observed. The sequential analysis showed that the sample size of this Meta-analysis had reached the expected value. Meanwhile, the grade of evidence quality suggested that the outcome indicators were mainly low or extremely low in quality. In conclusion, Bailing Capsules might have potential advantages in alleviating microinflammation, improving nutritional status, and reducing the incidence of cardiovascular events. However, in view of the low quality and evidence of the included literature, high-quality clinical trials are needed to further confirm the efficacy and safety of Bailing Capsules.


Assuntos
Doenças Cardiovasculares , Medicamentos de Ervas Chinesas , Cápsulas , Doenças Cardiovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Estado Nutricional , Diálise Renal/efeitos adversos
2.
Int J Biol Macromol ; 206: 481-488, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35245574

RESUMO

To obtain an analogue of pork backfat (PBF), we combined emulsion and gel to fabricate emulsion gel, which was prepared by using soybean protein isolate (SPI) and curdlan (CL) through a facile heat-treatment method in this paper. The microstructures, rheology properties, water holding capacity and freeze-thawing stability of the emulsion gel were investigated. The results suggested that the SPI/CL-stabilized emulsion gel was thermal-irreversible, and SPI was the emulsifying agent of the emulsion gel. Oil contents significantly affect the water holding capacity and freeze-thawing stability of emulsion gel. Subsequently, the TPA, gel strength and color of emulsion gels with different oil contents were compared with PBF. The hardness, chewiness, springiness, and gel strength of emulsion gel with 10 wt% oil contents were no significant differences from that of PBF (P > 0.05). Hence, this SPI/CL based emulsion gel can be used as an analogue to PBF, providing an alternative ingredient for the development of plant-based low-fat meat products.


Assuntos
Carne de Porco , Carne Vermelha , Animais , Emulsões , Géis/química , Proteínas de Soja/química , Suínos , Água , beta-Glucanas
3.
Acta Pharm Sin B ; 12(2): 735-746, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35256943

RESUMO

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and ß-catenin and inhibited AEC2 differentiation by disturbing the P300-ß-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.

4.
Clin Genet ; 101(4): 411-420, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35023146

RESUMO

Elevated serum uric acid (UA) level has been shown to be influenced by multiple genetic variants, but it remains uncertain how UA-associated variants differ in their influence on hyperuricemia risk in people taking antihypertensive drugs. We examined a total of 43 UA-related variants at 29 genes in 1840 patients with hypertension from a community-based longitudinal cohort during a median 2.25-year follow-up (including 1031 participants with normal UA, 440 prevalent hyperuricemia at baseline, and 369 new-onset hyperuricemia). Compared with the wild-type genotypes, patients carrying the SLC2A9 rs3775948G allele or the rs13129697G allele had decreased risk of hyperuricemia, while patients carrying the SLC2A9 rs11722228T allele had increased risk of hyperuricemia, after adjustment for cardiovascular risk factors and correction for multiple comparisons; moreover, these associations were modified by the use of diuretics, ß-blockers, or angiotensin converting enzyme inhibitors. The rs10821905A allele of A1CF gene was associated with increased risk of hyperuricemia, and this risk was enhanced by diuretics use. The studied variants were not observed to confer risk for incident cardiovascular events during the follow-up. In conclusion, the genes SLC2A9 and A1CF may serve as potential genetic markers for hyperuricemia risk in relation to antihypertensive drugs therapy in Chinese hypertensive patients.


Assuntos
Hipertensão , Hiperuricemia , Anti-Hipertensivos/efeitos adversos , Diuréticos/efeitos adversos , Proteínas Facilitadoras de Transporte de Glucose/genética , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Hiperuricemia/complicações , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Estudos Longitudinais , Fatores de Risco , Ácido Úrico/uso terapêutico
5.
J Am Chem Soc ; 144(3): 1087-1093, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35007081

RESUMO

Enantioselective [3 + 2] annulation of N-heteroarenes with alkynes has been developed via a cobalt-catalyzed dearomative umpolung strategy in the presence of chiral ligand and reducing reagent. A variety of electron-deficient N-heteroarenes, including quinolines, isoquinolines, quinoxaline, and pyridines, and internal or terminal alkynes are employed in this reaction, showing a broad substrate scope and good functionality tolerance. Annulation of electron-rich indoles with alkynes is also developed. This protocol provides a straightforward access to a variety of N-spiroheterocyclic molecules in excellent enantioselectivities (76 examples, up to 99% ee).

6.
J Hypertens ; 40(4): 749-757, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34980864

RESUMO

BACKGROUND: Evidence suggests that patients with higher blood pressure variability (BPV) have a higher risk for stroke but the relationship between BPV and stroke outcomes is unknown in those who underwent intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). The objective of this study is to investigate the association among BPV, BP values and stroke outcomes. METHODS: A retrospective analysis of about 510 consecutive thrombolysis cases for AIS from January 2015 to March 2019 in a single-center database were done. Then, these patients were followed-up for 3 months. We used univariate and multivariable models to evaluate the relationship between mean BP values, BPV and the risk of stroke outcomes from prior IVT to 72 h after IVT. Meanwhile, we also used COX regression to assess the hazard ratios of stroke outcomes with BPV within 3 months. Furthermore, we tested the effect of BP level at various time-points (prior to IVT and at 0, 2, 4, 8, 12, 24, 48 and 72 h after IVT) on development of postthrombolytic stroke outcomes. RESULTS: Higher BPV from prior IVT to 72 h after IVT was associated with higher risk of stroke outcomes within 3 months [SBPV of recurrent stroke: odds ratios (OR) = 5.298, 95% confidence interval (CI) 1.339-10.968, P = 0.018; DBPV of recurrent stroke: OR = 6.397, 95% CI 1.576-25.958, P = 0.009, respectively]. In addition, patients with recurrent stroke had significantly higher mean SBP (OR=1.037, 95% CI 1.006-1.069, P = 0.019). Furthermore, higher BP at different time points were associated with greater risk of recurrent stroke from prior IVT to 72 h after IVT. CONCLUSION: Higher BPV and SBP from prior IVT to 72 h after IVT was associated with higher risk of stroke outcomes within 3 months.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Pressão Sanguínea/fisiologia , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/efeitos adversos , Humanos , Prognóstico , Estudos Retrospectivos , Terapia Trombolítica , Resultado do Tratamento
7.
Sci Transl Med ; 14(626): eabf0992, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985967

RESUMO

High CD8+ T cell infiltration in colorectal cancer (CRC) should suggest a favorable prognosis and a satisfactory response to immunotherapy; however, the vast majority of patients with CRC do not benefit from immunotherapy due to poor T cell infiltration. Therefore, a better understanding of the mechanisms for T cell exclusion from CRC tumors is needed. Tribbles homolog 3 (TRIB3) has been implicated as an oncoprotein, but its role in regulating antitumor immune responses has not been defined. Here, we demonstrated that TRIB3 inhibits CD8+ T cell infiltration in various CRC mouse models. We showed that TRIB3 was acetylated by acetyltransferase P300, which inhibited ubiquitination and subsequent proteasomal degradation of TRIB3. Ectopically expressed TRIB3 inhibited signal transducer and activator of transcription 1 (STAT1) activation and STAT1-mediated CXCL10 transcription by enhancing the epidermal growth factor receptor signaling pathway, causing a reduction in tumor-infiltrating T cells. Genetic ablation of Trib3 or pharmacological acceleration of TRIB3 degradation with a P300 inhibitor increased T cell recruitment and sensitized CRCs to immune checkpoint blockade therapy. These findings identified TRIB3 as a negative modulator of CD8+ T cell infiltration in CRCs, highlighting a potential therapeutic target for treating immunologically "cold" CRCs.


Assuntos
Proteínas de Ciclo Celular , Neoplasias Colorretais , Evasão da Resposta Imune , Proteínas Repressoras , Animais , Linfócitos T CD8-Positivos , Proteínas de Ciclo Celular/metabolismo , Quimiocina CXCL10/metabolismo , Neoplasias Colorretais/patologia , Humanos , Imunoterapia , Camundongos , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais
8.
J Sci Food Agric ; 102(3): 949-956, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34302360

RESUMO

BACKGROUND: The waste of salted egg white resources has always been a serious problem in the food industry. In this current study, we report on a kind of Pickering emulsion system, which was stabilized by duck egg white nanogels (DEWNs) and sodium alginate (SA), followed by which this system was crosslinked by calcium carbonate (CaCO3 ) via controlling the gluconolactone (GDL) concentrations, aiming to open up a promising route for making full use of these protein resources. RESULTS: The droplet size of the emulsion exhibited a reduction with an increase in SA concentrations, indicating that higher negative charges and steric hindrance was useful for a stable emulsion system. Meanwhile, the result of rheology measurement showed that storage modulus (G') values were higher than loss modulus (G″) values of the samples at higher GDL concentration, revealing the formation of elastic gel-like networks in the system, which was fabricated by SA and Ca2+ released by the CaCO3 particles. The gel-like network structure in the continuous phase improved both the freeze-thaw and thermal stability of the obtained Pickering emulsion system. Encouragingly, the Pickering high internal phase emulsions (HIPEs, φ = 0.75) stabilized by DEWN/SA3 -GDL3 were prepared, which could be stored at 4 °C for at least 30 days without oiling-off and creaming. CONCLUSION: These findings not only develop a green ultra-stable Pickering emulsion system but also extend the potential commercial applications of duck egg white proteins in the food, cosmetics, and pharmaceutical industries. © 2021 Society of Chemical Industry.


Assuntos
Alginatos/química , Clara de Ovo/química , Nanogéis/química , Animais , Patos , Proteínas do Ovo/química , Emulsões/química , Reologia , Resíduos/análise
9.
Chin J Integr Med ; 28(3): 236-242, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34897590

RESUMO

OBJECTIVE: To elucidate the mechanisms of 4 effective components from a Chinese medicine formula, namely Qingre Huoxue Jiedu Formula (QHJ heat- and toxin-clearing and blood-activating formula), in the treatment of nerve growth factor (NGF)-induced psoriasis. METHODS: Keratinocyte proliferation and T cell proliferation models were developed using NGF. An NGF solution (NGF+DMEM, 100 ng/mL) was added to all induced groups and treated groups and were cultured for 24 h, while a solution with NTRK1 antagonist (K252a+DEME, 300 nmol/L) was added and cultured for 1 h. The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ, namely shikonin, paeonol, astilbin and ursolic acid. Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay, respectively. The mRNA expression levels of Bax, Bcl-xl, and NGF receptor (NGFR) were assessed by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. RESULTS: (1) All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups (P<0.05). In addition, treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only (P<0.05), particularly in cells treated with ursolic acid. (2) QHJ-treated groups showed higher protein expression levels of Bax, Bcl-xl compared with other groups (P<0.05). Additionally, treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax, Bcl-xl and NGFR compared with those treated with QHJ only (all P<0.05), especially in those treated with shikonin. CONCLUSION: The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation, and upregulating the expression level of Bax, Bcl-xl and NGFR.


Assuntos
Medicamentos de Ervas Chinesas , Psoríase , Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Fator de Crescimento Neural/metabolismo , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico
10.
Cell Death Dis ; 12(11): 1056, 2021 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-34743197

RESUMO

The delivery of biomolecules by extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs) has been proven to ameliorate sepsis, yet the therapeutic mechanism remains to be elucidated. Taurine upregulated gene 1 (TUG1) is a long noncoding RNA (lncRNA) that is downregulated in sepsis. The current study was designed to explore the role of EPCs derived EVs transmitting TUG1 in macrophage polarization and macrophage-mediated inflammation in a cecal ligation and puncture (CLP)-induced sepsis mouse model. TUG1 was underexpressed in CLP-induced sepsis, and its reexpression induced anti-inflammatory macrophage polarization and suppressed macrophage-medicated inflammatory injury to the pulmonary vascular endothelium. EPCs derived EVs transmitted TUG1 to promote M2 macrophage polarization. Luciferase, RIP, and RNA pull-down assays showed that TUG1 could competitively bind to microRNA-9-5p (miR-9-5p) to upregulate the expression of sirtuin 1 (SIRT1). Furthermore, EPCs derived EVs transmitted TUG1 to promote M2 macrophage polarization through the impairment of miR-9-5p-dependent SIRT1 inhibition. Finally, EPCs derived EVs carrying TUG1 were verified to ameliorate sepsis-induced organ damage in the murine model. In summary, EPCs derived EVs transmit TUG1 to attenuate sepsis via macrophage M2 polarization. This study also highlights the proinflammatory mechanism associated with miR-9-5p-mediated inhibition of SIRT1, which contributes to a more comprehensive understanding of the pathogenesis of sepsis.


Assuntos
Anti-Inflamatórios/metabolismo , Polaridade Celular , Células Progenitoras Endoteliais/metabolismo , Vesículas Extracelulares/metabolismo , Macrófagos/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Sepse/genética , Sirtuína 1/metabolismo , Animais , Sequência de Bases , Polaridade Celular/genética , Modelos Animais de Doenças , Inflamação/genética , Inflamação/patologia , Pulmão/irrigação sanguínea , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Modelos Biológicos , Tamanho da Partícula , Ligação Proteica , Células RAW 264.7 , RNA Longo não Codificante/genética , Sepse/patologia , Regulação para Cima/genética
11.
J Clin Hypertens (Greenwich) ; 23(12): 2089-2099, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34783432

RESUMO

To investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single-center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP < 140 mm Hg and DBP < 90 mm Hg), Group 2: (SBP: 140-159 mm Hg and or DBP: 90-99 mm Hg), and Group 3: (SBP ≥160 mm Hg and/or DBP ≥100 mm Hg) according to the guidelines. The associations of mean BP levels and variability with outcomes (recurrent stroke, all-cause death and the composite cardiovascular events) at 6 months were analyzed by Cox proportional hazard models. The associations of BP variability with BP levels and cerebral blood flow (CBF) were analyzed by linear regression and generalized additive models. Both for primary and secondary outcome, more events occurred in Group 1 compared with Group 2, while no significant difference was found in Group 3 with higher BP levels. Lower systolic BP variability showed better prognosis and higher CBF. The associations were more significant in patients with CAS ≥50%. BP variability exhibited a linear negative relationship with BP levels. In the early phase of AIS with hypertension and CAS, maintaining low blood pressure variability may be important to improve outcomes while low BP levels (SBP/DBP < 140/90 mm Hg) were harmful, especially in those patients with CAS ≥ 50%.


Assuntos
Isquemia Encefálica , Estenose das Carótidas , Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Pressão Sanguínea , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/epidemiologia , Estudos de Coortes , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
12.
Acta Pharm Sin B ; 11(10): 3105-3119, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34729304

RESUMO

Pulmonary fibrosis (PF) is a chronic, progressive, fatal interstitial lung disease with limited available therapeutic strategies. We recently reported that the protein kinase glycogen synthase kinase-3ß (GSK-3ß) interacts with and inactivates the ubiquitin-editing enzyme A20 to suppress the degradation of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPß) in alveolar macrophages (AMs), resulting in a profibrotic phenotype of AMs and promoting the development of PF. Here, we showed that chronic lung injury upregulated the stress response protein tribbles homolog 3 (TRIB3), which interacted with GSK-3ß and stabilized GSK-3ß from ubiquitination and degradation. Elevated GSK-3ß expression phosphorylated A20 to inhibit its ubiquitin-editing activity, causing the accumulation of C/EBPß and the production of several profibrotic factors in AMs and promoting PF development. Activated C/EBPß, in turn, increased the transcription of TRIB3 and GSK-3ß, thereby establishing a positive feedback loop in AMs. The knockdown of TRIB3 expression or the pharmacologic disruption of the TRIB3‒GSK-3ß interaction was an effective PF treatment. Our study reveals an intact profibrotic axis of TRIB3‒GSK-3ß‒A20‒C/EBPß in AMs, which represents a target that may provide a promising treatment strategy for PF.

15.
Immunity ; 54(9): 2042-2056.e8, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34407391

RESUMO

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4+ T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1. Mass spectrometry analyses of CCL1 complexes identified AMFR as a CCL1 receptor, and deletion of Amfr impaired fibroblast activation. Mechanistically, CCL1 binding triggered ubiquitination of the ERK inhibitor Spry1 by AMFR, thus activating Ras-mediated profibrotic protein synthesis. Antibody blockade of CCL1 ameliorated PF pathology, supporting the therapeutic potential of targeting this pathway for treating fibroproliferative lung diseases.


Assuntos
Quimiocina CCL1/metabolismo , Fibroblastos/metabolismo , Proteínas de Membrana/metabolismo , Miofibroblastos/metabolismo , Fosfoproteínas/metabolismo , Fibrose Pulmonar/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Diferenciação Celular/fisiologia , Fibroblastos/patologia , Humanos , Camundongos , Miofibroblastos/patologia , Fibrose Pulmonar/patologia , Transdução de Sinais/fisiologia
17.
Plant Physiol Biochem ; 166: 958-963, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34256249

RESUMO

Nitrate plays both nutritional and osmotic roles in the salt tolerance of halophytes. However, how halophytes take up NO3- under saline conditions is still not well understood. Seedlings of Suaeda salsa L. were treated with 0, 200 and 500 mM NaCl under 0.5 mM NO3--N with or without Na3VO4 (the inhibitor of plasma membrane H+-ATPase) for 24 h. Salinity treatment of 200 mM NaCl up-regulated the gene expression of nitrate transporter 2.1 (SsNRT2.1) in the roots, increased the root net influx of H+ and NO3- and 15NO3- accumulation in the leaves and roots. The expression of SsNRT2.1 at 200 mM NaCl with Na3VO4 was much higher than that without supplying Na3VO4, and the opposite trend was found in 15NO3- accumulation in the leaves and roots. Supplying Na3VO4 had no significant effect on the net H+ flux, but induced a net NO3- efflux in the roots at 200 mM NaCl. Salinity may directly activate the expression of SsNRT2.1 and promote NO3- uptake via the increment of pumping H+ by PM H+-ATPase in S. salsa, which may explain why certain halophytes can absorb and accumulate high concentration of NO3- under low NO3- and high salinity conditions.


Assuntos
Chenopodiaceae , Salinidade , Nitratos , Tolerância ao Sal , Plantas Tolerantes a Sal
18.
ACS Omega ; 6(12): 8616-8624, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33817522

RESUMO

A new fluorescent probe LXY based on the rhodamine 6G platforms has been designed, synthesized, and characterized, which could recognize Fe3+ effectively in HEPES buffer (10 mM, pH = 7.4)/CH3CN (2:3, v/v). And the distinct color change and the rapid emergence of fluorescence emission at 550 nm achieved "naked eye" detection of Fe3+. The interaction mode between them was achieved by Job's plot, MS, SEM, and X-ray single-crystal diffraction. Importantly, the crystal structures proved that Fe3+ could induce the rhodamine moiety transform the closed-cycle form to the open-cycle form. But it is interesting that Fe3+ did not appear in the crystal structures. Meanwhile, the limit of detection (LOD) of LXY to Fe3+ was calculated to be 3.47 × 10-9. In addition, the RGB experiment, test papers, and silica gel plates all indicated that the probe LXY could be used to distinguish Fe3+ quantitatively and qualitatively on-site. Moreover, the probe LXY has also been successfully applied to Fe3+ image in Caenorhabditis elegans, adult mice, and plant tissues. Thus, LXY was considered to have some potential for application in bioimaging.

19.
Sci Transl Med ; 13(586)2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762435

RESUMO

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which have the worst prognosis and distant metastasis-free survival among breast cancer subtypes. Now, no targeted therapies are available for patients with BLBC due to the lack of reliable and effective molecular targets. Here, we performed the BLBC tissue microarray-based immunohistochemical analysis and showed that Faciogenital Dysplasia 5 (FGD5) abundance is associated with poor prognosis in BLBCs. FGD5 deletion decreased the proliferation, invasion, and tumorsphere formation capacity of BLBC cells. Furthermore, genetic inhibition of Fgd5 in mouse mammary epithelial cells attenuated BLBC initiation and progression by reducing the self-renewal ability of tumor-initiating cells. In addition, FGD5 abundance was positively correlated with the abundance of epidermal growth factor receptor (EGFR) in BLBCs. FGD5 ablation decreased EGFR abundance by reducing EGFR stability in TNBC cells in 2D and 3D culture conditions. Mechanistically, FGD5 binds to EGFR and interferes with basal EGFR ubiquitination and degradation induced by the E3 ligase ITCH. Impaired EGFR degradation caused BLBC cell proliferation and promoted invasive properties and self-renewal. To verify the role of the FGD5-EGFR interaction in the regulation of EGFR stability, we screened a cell-penetrating α-helical peptide PER3 binding with FGD5 to disrupt the interaction. Treatment of BLBC patient-derived xenograft-bearing mice with the peptide PER3 disrupting the FGD5-EGFR interaction either with or without chemotherapy reduced BLBC progression. Our study identified FGD5 as a positive modulator of tumor-initiating cells and suggests a potential therapeutic option for the BLBC subtype of breast cancer.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Células-Tronco Neoplásicas , Neoplasias de Mama Triplo Negativas , Animais , Receptores ErbB , Feminino , Humanos , Camundongos , Neoplasias de Mama Triplo Negativas/genética
20.
Brain ; 144(9): 2648-2658, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33729480

RESUMO

Cavernous malformations affecting the CNS occur in ∼0.16-0.4% of the general population. The majority (85%) of cavernous malformations are in a sporadic form, but the genetic background of sporadic cavernous malformations remains enigmatic. Of the 81 patients, 73 (90.1%) patients were detected carrying somatic missense variants in two genes: MAP3K3 and PIK3CA by whole-exome sequencing. The mutation spectrum correlated with lesion size (P = 0.001), anatomical distribution (P < 0.001), MRI appearance (P = 0.004) and haemorrhage events (P = 0.006). PIK3CA mutation was a significant predictor of overt haemorrhage events (P = 0.003, odds ratio = 11.252, 95% confidence interval = 2.275-55.648). Enrichment of endothelial cell population was associated with a higher fractional abundance of the somatic mutations. Overexpression of the MAP3K3 mutation perturbed angiogenesis of endothelial cell models in vitro and zebrafish embryos in vivo. Distinct transcriptional signatures between different genetic subgroups of sporadic cavernous malformations were identified by single cell RNA sequencing and verified by pathological staining. Significant apoptosis in MAP3K3 mutation carriers and overexpression of GDF15 and SERPINA5 in PIK3CA mutation carriers contributed to their phenotype. We identified activating MAP3K3 and PIK3CA somatic mutations in the majority (90.1%) of sporadic cavernous malformations and PIK3CA mutations could confer a higher risk for overt haemorrhage. Our data provide insights into genomic landscapes, propose a mechanistic explanation and underscore the possibility of a molecular classification for sporadic cavernous malformations.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/genética , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/genética , MAP Quinase Quinase Quinase 3/genética , Mutação/genética , Medula Espinal/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Peixe-Zebra
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