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1.
J Plant Physiol ; 295: 154205, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437759

RESUMO

Ammonium (NH4+) concentrations in rice fields show heterogeneous spatial distribution under the combined influences of nitrogen fertilizer application and modern agronomic practices. However, the characteristics and mechanisms of rice roots in response to heterogeneous NH4+ supply are not well understood. Here, we found a systemic response of rice roots to heterogeneous and high (10 mM) NH4+ supply using a split-root experiment, and show root growth on the NH4+-free (NO3-) side was also inhibited by localized high-NH4+ supply. Moreover, OsEIL1 (encoding a core transcription factor in the ethylene signaling pathway) was found to be involved in the response of rice roots to heterogeneous NH4+. OsEIL1 mutation significantly increased the inhibitory effect of localized high-NH4+ on root growth of the NO3- side, as well as significantly increased NH4+ efflux there. Furthermore, our results indicate that the mitigating effect of OsEIL1 on NH4+ efflux is related to the regulated expression of OsVTC1-3 (encoding a GDP-mannose pyrophosphorylase). These findings provide insight into the mechanisms by which OsEIL1 responds to heterogeneous high NH4+ and contribute to our understanding of rice adaptation to heterogeneous NH4+ supply.


Assuntos
Compostos de Amônio , Oryza , Compostos de Amônio/metabolismo , Oryza/metabolismo , Fatores de Transcrição/metabolismo , Nitrogênio/metabolismo , Raízes de Plantas/metabolismo , Nitratos/metabolismo
2.
Heliyon ; 10(4): e26070, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420419

RESUMO

Anterior cruciate ligament (ACL) tear is a common sports-related injury, and cartilage injury always emerges as a serious complication following ACL tear, significantly impacting the physical and psychological well-being of affected individuals. Over the years, efforts have been directed toward finding strategies to repair cartilage injury after ACL tear. In recent times, procyanidins, known for their anti-inflammatory and antioxidant properties, have emerged as potential key players in addressing this concern. This article focuses on summarizing the research progress of procyanidins in repairing cartilage injury after ACL tear. It covers the roles, mechanisms, and clinical significance of procyanidins in repairing cartilage injury following ACL tear and explores the future prospects of procyanidins in this domain. This review provides novel insights and hope for the repair of cartilage injury following ACL tear.

3.
Plant Physiol ; 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38401163

RESUMO

Improving nitrogen-use efficiency (NUE) is an important path toward enhancing crop yield and alleviating the environmental impacts of fertilizer use. Ammonium (NH4+) is the energetically preferred inorganic N source for plants. The interaction of NH4+ with other nutrients is a chief determinant of ammonium-use efficiency (AUE) and of the tipping point toward ammonium toxicity, but these interactions have remained ill-defined. Here, we report that iron (Fe) accumulation is a critical factor determining AUE and have identified a substance that can enhance AUE by manipulating Fe availability. Fe accumulation under NH4+ nutrition induces NH4+ efflux in the root system, reducing both growth and AUE in Arabidopsis (Arabidopsis thaliana). Low external availability of Fe and a low plant Fe status substantially enhance protein N-glycosylation through a Vitamin C1 (VTC1)-independent pathway, thereby reducing NH4+ efflux to increase AUE during the vegetative stage in Arabidopsis under elevated NH4+ supply. We confirm the validity of the iron-ammonium interaction in the important crop species lettuce (Lactuca sativa). We further show that dolomite can act as an effective substrate to subdue Fe accumulation under NH4+ nutrition by reducing the expression of Low Phosphate Root 2 (LPR2) and acidification of the rhizosphere. Our findings present a strategy to improve AUE and reveal the underlying molecular-physiological mechanism.

4.
J Exp Bot ; 74(19): 6131-6144, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37279530

RESUMO

Plant growth and development depend on sufficient nutrient availability in soils. Agricultural soils are generally nitrogen (N) deficient, and thus soils need to be supplemented with fertilizers. Ammonium (NH4+) is a major inorganic N source. However, at high concentrations, NH4+ becomes a stressor that inhibits plant growth. The cause of NH4+ stress or toxicity is multifactorial, but the interaction of NH4+ with other nutrients is among the main determinants of plants' sensitivity towards high NH4+ supply. In addition, NH4+ uptake and assimilation provoke the acidification of the cell external medium (apoplast/rhizosphere), which has a clear impact on nutrient availability. This review summarizes current knowledge, at both the physiological and the molecular level, of the interaction of NH4+ nutrition with essential mineral elements that are absorbed as cations, both macronutrients (K+, Ca2+, Mg2+) and micronutrients (Fe2+/3+, Mn2+, Cu+/2+, Zn2+, Ni2+). We hypothesize that considering these nutritional interactions, and soil pH, when formulating fertilizers may be key in order to boost the use of NH4+-based fertilizers, which have less environmental impact compared with nitrate-based ones. In addition, we are convinced that better understanding of these interactions will help to identify novel targets with the potential to improve crop productivity.

5.
Phys Rev Lett ; 130(6): 066302, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36827579

RESUMO

A Coulomb blockaded M-Majorana island coupled to normal metal leads realizes a novel type of Kondo effect where the effective impurity "spin" transforms under the orthogonal group SO(M). The impurity spin stems from the nonlocal topological ground state degeneracy of the island and thus the effect is known as the topological Kondo effect. We introduce a physically motivated N-channel generalization of the topological Kondo model. Starting from the simplest case N=2, we conjecture a stable intermediate coupling fixed point and evaluate the resulting low-temperature impurity entropy. The impurity entropy indicates that an emergent Fibonacci anyon can be realized in the N=2 model. We also map the case N=2, M=4 to the conventional four-channel Kondo model and find the conductance at the intermediate fixed point. By using the perturbative renormalization group, we also analyze the large-N limit, where the fixed point moves to weak coupling. In the isotropic limit, we find an intermediate stable fixed point, which is stable to "exchange" coupling anisotropies, but unstable to channel anisotropy. We evaluate the fixed point impurity entropy and conductance to obtain experimentally observable signatures of our results. In the large-N limit, we evaluate the full crossover function describing the temperature-dependent conductance.

6.
Urol Int ; 107(2): 214-218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35158355

RESUMO

Renal arteriovenous malformation (RAVM) is a rare pathology. It may present with heamturia, hypertension, and congestive heart failure. Digital subtraction angiography (DSA) is the standard diagnostic choice, and endovascular embolization is a preferred procedure of management in most cases. The feeding branches of RAVM are reported to originate from renal arteries. In this report, a 43-year-old female with recurrent massive hematuria and left flank pain was described. Renal angiography revealed double renal arteries supplying the left kidney and multiple renal arteriovenous fistula formation around the renal pelvis. Embolization with coils and gelfoam was performed after which her hematuria subsided. One month later, the patient was readmitted to our hospital due to the relapse of massive hematuria following heavy physical activities. DSA found another feeding artery of the RAVM originating from the aorta around the 4th lumbar vertebra. After embolization of this arterial feeder, hematuria settled. There was no recurrence during a 10-month follow-up. To our knowledge, this is the first case of RAVM with an extrarenal feeding artery, and omission of this scenario can lead to treatment failure.


Assuntos
Malformações Arteriovenosas , Embolização Terapêutica , Nefropatias , Doenças Ureterais , Humanos , Feminino , Adulto , Hematúria/etiologia , Hematúria/terapia , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/terapia , Rim , Nefropatias/complicações , Artéria Renal/diagnóstico por imagem , Falha de Tratamento , Doenças Ureterais/complicações , Embolização Terapêutica/métodos
8.
Technol Cancer Res Treat ; 21: 15330338221117386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35950243

RESUMO

Osteosarcoma is one of the most common primary malignant bone tumors, mainly occurring in children and adolescents, and is characterized by high morbidity and poor prognosis. MicroRNAs, a class of noncoding RNAs consisting of 19 to 25 nucleotides, are involved in cell proliferation, invasion, metastasis, and apoptosis to regulate the development and progression of osteosarcoma. Studies have found that microRNAs are closely related to the diagnosis, treatment, and prognosis of osteosarcoma patients and have an important role in improving drug resistance in osteosarcoma. This paper reviews the role of microRNAs in the pathogenesis of osteosarcoma and their clinical value, aiming to provide a new research direction for diagnosing and treating osteosarcoma and achieving a better prognosis.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , Adolescente , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Criança , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Osteossarcoma/patologia , Prognóstico
9.
BMC Urol ; 22(1): 66, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440078

RESUMO

BACKGROUND: Hem-o-Lok clips (HOLCs) are widely used in minimal access urological operations due to the advantage of vascular control and suture stabilization. In rare cases, however, they can develop problems themselves. Migration of HOLCs into the collecting system is a fairly rare complication after laparoscopic pyelolithotomy. To date, only two cases were reported in the literature. CASE PRESENTATION: This article describes a case of 51-year-old man with a complaint of left flank pain. He had a medical history of ipsilateral retroperitoneal laparoscopic pyelolithotomy at another hospital 8 years ago. Non-contrast CT scan demonstrated a renal stone in the left ureteropelvic junction complicated by mild hydronephrosis. A straight foreign body was found near the renal pelvis, with part of it wedging into renal pelvic wall. A percutaneous nephrolithotomy (PNL) was performed for this patient. After some fragmentation, a HOLC was found in the kernel of the stone. With an alligator plier, the clip was totally removed out of the collecting system. The postoperative period and follow-up were uneventful. CONCLUSIONS: HOLC migration into renal pelvis is a rare complication following laparoscopic pyelolithotomy. It could act as nidus for stone formation under extended exposure to urine. Using HOLCs to stabilize the anastomotic suture near renal pelvis should be avoided to prevent this complication. Instead, knotting is a better choice under such condition. The secondary calculi and dislodged HOLCs can be removed through PNL by an alligator plier after laser lithotripsy.


Assuntos
Cálculos Renais , Laparoscopia , Feminino , Humanos , Cálculos Renais/cirurgia , Pelve Renal , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Espaço Retroperitoneal , Instrumentos Cirúrgicos
10.
J Colloid Interface Sci ; 618: 11-21, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35316708

RESUMO

The redox state disorder of biological system caused by oxidative stress can lead to a variety of clinical dysfunction and diseases. It is an important challenge to find artificial materials that can efficiently adjust the redox balance to maintain health. In this work, a nitrogen-doped carbon (NCDs) redox nanozyme loaded into metal organic framework (MOF, UiO-66) is designed to form NCDs/UiO-66 nanocomposites. The high specific surface area and porosity of UiO-66 serve as ideal carrier to support multifunctional NCDs. NCDs/UiO-66 nanocomposites are comprehensively investigated for their ability to scavenge or generate reactive oxygen species (ROS) and free radicals. Experimental results demonstrate that NCDs/UiO-66 can remove intrinsic free radicals (•OH, O2•- and ABTS•+), exhibiting superoxide dismutase-like activity and antioxidant capability. Moreover, NCDs/UiO-66 can efficiently produce ROS (•OH, O2•- and 1O2) under irradiation showing light induced oxidase-like activity and pro-oxidant capability. This suggests the anti-oxidant and pro-oxidant activities of NCDs/UiO-66 could be regulated easily by light irradiation. Using the fluorescent property and light-activated oxidase-like activity of NCDs/UiO-66, the methods for detection of ferric ion (Fe3+) and glutathione (GSH) are developed.


Assuntos
Estruturas Metalorgânicas , Antioxidantes , Carbono , Radicais Livres , Glutationa , Ferro , Nitrogênio , Oxirredução , Oxirredutases , Ácidos Ftálicos , Espécies Reativas de Oxigênio
11.
Ecol Evol ; 12(1): e8286, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35136541

RESUMO

In general, it is accepted that gap formation significantly affects the placement of scatter-hoarded seeds by small rodents, but the effects of different forest gap sizes on the seed-eating and scatter-hoarding behaviors of small rodents remain unclear. Thus, we examined the effects of a closed-canopy forest, forest edge, and gaps with different sizes on the spatial dispersal of Quercus variabilis acorns and cache placement by small rodents using coded plastic tags in the Taihang Mountains, China. The seeds were removed rapidly, and there were significant differences in the seed-eating and caching strategies between the stand types. We found that Q. variabilis acorns were usually eaten after being removed from the closed-canopy forest and forest edges. By contrast, the Q. variabilis acorns in the forest gap stands were more likely to be scatter-hoarded. The dispersal distances of Q. variabilis acorns were significantly longer in the forest gap plots compared with the closed canopy and forest edge plots. However, the proportion of scatter-hoarded seeds did not increase significantly as the gap size increased. In small-scale oak reforestation projects or research, creating small gaps to promote rodent-mediated seed dispersal may effectively accelerate forest recovery and successional processes.

12.
Plant Cell Environ ; 45(5): 1537-1553, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35133011

RESUMO

Rice is known for its superior adaptation to ammonium (NH4+ ) as a nitrogen source. Compared to many other cereals, it displays lower NH4+ efflux in roots and higher nitrogen-use efficiency on NH4+ . A critical role for GDP-mannose pyrophosphorylase (VTC1) in controlling root NH4+ fluxes was previously documented in Arabidopsis, but the molecular pathways involved in regulating VTC1-dependent NH4+ efflux remain unclear. Here, we report that ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1) acts as a key transcription factor regulating OsVTC1-3-dependent NH4+ efflux and protein N-glycosylation in rice grown under NH4+ nutrition. We show that OsEIL1 in rice plays a contrasting role to Arabidopsis-homologous ETHYLENE-INSENSITIVE3 (AtEIN3) and maintains rice growth under NH4+ by stabilizing protein N-glycosylation and reducing root NH4+ efflux. OsEIL1 constrains NH4+ efflux by activation of OsVTC1-3, but not OsVTC1-1 or OsVTC1-8. OsEIL1 binds directly to the promoter EIN3-binding site (EBS) of OsVTC1-3 in vitro and in vivo and acts to increase the transcription of OsVTC1-3. Our work demonstrates an important link between excessive root NH4+ efflux and OsVTC1-3-mediated protein N-glycosylation in rice grown under NH4+ nutrition and identifies OsEIL1 as a direct genetic regulator of OsVTC1-3 expression.


Assuntos
Compostos de Amônio , Arabidopsis , Oryza , Compostos de Amônio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Glicosilação , Nitrogênio/metabolismo , Oryza/metabolismo , Raízes de Plantas/metabolismo
13.
New Phytol ; 232(1): 190-207, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34128546

RESUMO

Ammonium (NH4+ ) is toxic to root growth in most plants, even at moderate concentrations. Transcriptional regulation is one of the most important mechanisms in the response of plants to NH4+ toxicity, but the nature of the involvement of transcription factors (TFs) in this regulation remains unclear. Here, RNA-seq analysis was performed on Arabidopsis roots to screen for ammonium-responsive TFs. WRKY46, the member of the WRKY transcription factor family most responsive to NH4+ , was selected. We defined the role of WRKY46 using mutation and overexpression assays, and characterized the regulation of NUDX9 and indole-3-acetic acid (IAA)-conjugating genes by WRKY46 via yeast one-hybrid and electrophoretic mobility shift assays and chromatin immunoprecipitation-quantitative real-time polymerase chain reaction (ChIP-qPCR). Knockout of WRKY46 increased, while overexpression of WRKY46 decreased, NH4+ -suppression of the primary root. WRKY46 is shown to directly bind to the promoters of the NUDX9 and IAA-conjugating genes (GH3.1, GH3.6, UGT75D1, UGT84B2) and to inhibit their transcription, thus positively regulating free IAA content and stabilizing protein N-glycosylation, leading to an inhibition of NH4+ efflux in the root elongation zone (EZ). We identify TF involvement in the regulation of NH4+ efflux in the EZ, and show that WRKY46 inhibits NH4+ efflux by negative regulation of NUDX9 and IAA-conjugating genes.


Assuntos
Compostos de Amônio , Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos , Raízes de Plantas/genética , Raízes de Plantas/metabolismo
14.
J Plant Physiol ; 261: 153415, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33894579

RESUMO

Ammonium (NH4+) inhibits primary root (PR) growth in most plant species when present even at moderate concentrations. Previous studies have shown that transport of indole-3-acetic acid (IAA) is critical to maintaining root elongation under high-NH4+ stress. However, the precise regulation of IAA homeostasis under high-NH4+ stress (HAS) remains unclear. In this study, qRT-PCR, RNA-seq, free IAA and IAA conjugate and PR elongation measurements were conducted in genetic mutants to investigate the role of IAA biosynthesis and conjugation under HAS. Our data clearly show that HAS decreases free IAA in roots by increasing IAA inactivation but does not decrease IAA biosynthesis, and that the IAA-conjugating genes GH3.1, GH3.2, GH3.3, GH3.4, and GH3.6 function as the key genes in regulating high-NH4+ sensitivity in the roots. Furthermore, the analysis of promoter::GUS staining in situ and genetic mutants reveals that HAS promotes IAA conjugation in the elongation zone (EZ), which may be responsible for the PR inhibition observed under HAS. This study provides potential new insight into the role of auxin in the improvement of tolerance to NH4+.


Assuntos
Compostos de Amônio/metabolismo , Arabidopsis/crescimento & desenvolvimento , Ácidos Indolacéticos/farmacologia , Raízes de Plantas/crescimento & desenvolvimento , Compostos de Amônio/administração & dosagem , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Homeostase/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Estresse Fisiológico
15.
J Exp Bot ; 72(12): 4548-4564, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33772588

RESUMO

Ammonium (NH4+) is toxic to root growth in most plants already at moderate levels of supply, but mechanisms of root growth tolerance to NH4+ remain poorly understood. Here, we report that high levels of NH4+ induce nitric oxide (NO) accumulation, while inhibiting potassium (K+) acquisition via SNO1 (sensitive to nitric oxide 1)/SOS4 (salt overly sensitive 4), leading to the arrest of primary root growth. High levels of NH4+ also stimulated the accumulation of GSNOR (S-nitrosoglutathione reductase) in roots. GSNOR overexpression improved root tolerance to NH4+. Loss of GSNOR further induced NO accumulation, increased SNO1/SOS4 activity, and reduced K+ levels in root tissue, enhancing root growth sensitivity to NH4+. Moreover, the GSNOR-like gene, OsGSNOR, is also required for NH4+ tolerance in rice. Immunoblotting showed that the NH4+-induced GSNOR protein accumulation was abolished in the VTC1- (vitamin C1) defective mutant vtc1-1, which is hypersensititive to NH4+ toxicity. GSNOR overexpression enhanced vtc1-1 root tolerance to NH4+. Our findings suggest that induction of GSNOR increases NH4+ tolerance in Arabidopsis roots by counteracting NO-mediated suppression of tissue K+, which depends on VTC1 function.


Assuntos
Compostos de Amônio , Arabidopsis , Oryza , Aldeído Oxirredutases/genética , Arabidopsis/genética , Proteínas de Arabidopsis , Glutationa Redutase , Homeostase , Oryza/genética , Oxirredutases , Potássio , S-Nitrosoglutationa
16.
Arthritis Res Ther ; 22(1): 269, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198785

RESUMO

BACKGROUND: Osteogenic differentiation is an essential process for bone regeneration involving bone marrow mesenchymal stem cells (BMSCs). BMSC-secreted extracellular vesicles (EVs) enriched with microRNAs (miRs) have vital roles to play in mediating osteogenic differentiation. Therefore, this study aimed to explore the effect of BMSC-derived EVs loaded with miR-15b on osteogenic differentiation. METHODS: Human BMSCs (hBMSCs) were cultured and treated with plasmids overexpressing or knocking down KLF2, WWP1, and miR-15b to define the role of derived EVs in osteogenic differentiation in vitro. The expression of osteogenic differentiation-related marker was measured by Western blot analysis. The interaction among miR-15b, WWP1, and ubiquitination of KLF2 was investigated by dual-luciferase reporter, immunoprecipitation, and GST pull-down assays. Moreover, EVs from hBMSCs transfected with miR-15b inhibitor (EV-miR-15b inhibitor) were injected into ovariectomized rats to verify the effect of miR-15b on bone loss in vivo. RESULTS: WWP1 was downregulated, and KLF2 was upregulated during osteogenic differentiation. After co-culture with EVs, miR-15b expression was elevated and WWP1 expression was reduced in hBMSCs. Upregulation of miR-15b or KLF2 or downregulation of WWP1 or NF-κB increased ALP activity and cell mineralization, as well as osteogenic differentiation-related marker expression in hBMSCs. Mechanistically, miR-15b targeted and inhibited WWP1, thus attenuating KLF2 degradation and inhibiting NF-κB activity. Co-culture of EVs increased the bone volume and trabecular number, but decreased bone loss in ovariectomized rats, which could be reversed after treatment with EV-miR-15b inhibitor. CONCLUSION: Collectively, BMSC-derived EVs loaded with miR-15b promoted osteogenic differentiation by impairing WWP1-mediated KLF2 ubiquitination and inactivating the NF-κB signaling pathway.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Animais , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Fatores de Transcrição Kruppel-Like/genética , MicroRNAs/genética , Osteogênese/genética , Ratos , Ubiquitina-Proteína Ligases
17.
Stem Cell Res Ther ; 11(1): 227, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522250

RESUMO

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) exhibit the capacity to self-renew and differentiate into multi-lineage cell types, including osteoblasts, which are crucial regulators of fracture healing. Thus, this study aims to investigate the effect of microRNA (miR)-22-3p from BMSC-derived EVs on osteogenic differentiation and its underlying mechanism. METHODS: Extracellular vesicles (EVs) were isolated from BMSCs and taken up with BMSCs. Dual-luciferase reporter gene assay was used to verify the binding relationship between miR-22-3p and FTO. Loss- and gain-of-function experiments were performed to determine the roles of EV-delivered miR-22-3p and FTO in osteogenic differentiation as well as their regulatory role in the MYC/PI3K/AKT axis. To determine the osteogenic differentiation, ALP and ARS stainings were conducted, and the levels of RUNX2, OCN, and OPN level were determined. In vivo experiment was conducted to determine the function of EV-delivered miR-22-3p and FTO in osteogenic differentiation, followed by ALP and ARS staining. RESULTS: miR-22-3p expression was repressed, while FTO expression was elevated in the ovariectomized mouse model. Overexpression of miR-22-3p, EV-delivered miR-22-3p, increased ALP activity and matrix mineralization of BMSCs and promoted RUNX2, OCN, and OPN expressions in BMSCs. miR-22-3p negatively targeted FTO expression. FTO silencing rescued the suppressed osteogenic differentiation by EV-delivered miR-22-3p inhibitor. FTO repression inactivated the MYC/PI3K/AKT pathway, thereby enhancing osteogenic differentiation both in vivo and in vitro. CONCLUSION: In summary, miR-22-3p delivered by BMSC-derived EVs could result in the inhibition of the MYC/PI3K/AKT pathway, thereby promoting osteogenic differentiation via FTO repression.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Animais , Diferenciação Celular , Células Cultivadas , Camundongos , MicroRNAs/genética , Osteogênese/genética , Fosfatidilinositol 3-Quinases
18.
ACS Sens ; 5(6): 1726-1733, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32441104

RESUMO

Hyaluronidase 1 (Hyal-1) is an important enzyme involved in intracellular hyaluronic acid (HA) catabolism for performing various physiological functions, and its aberrant level is closely associated with many malignant diseases. Bioluminescence imaging is advantageous for monitoring Hyal-1 activity in vivo, but it remains challenging to design an available probe for differentiating Hyal-1 from other isoforms by a traditional strategy that covalently masks the firefly luciferase substrate. Herein, we, for the first time, present a noncovalently caging approach to construct a Hyal-1-specific bioluminogenic nanosensor by entrapping d-luciferin (d-Luc) inside the cholesterylamine-modified HA (CHA) nanoassembly to inhibit the bioluminescence production. When encountered with intracellular Hyal-1, CHA could be fully dissembled to liberate multiple copies of the loaded d-Luc, thereby emitting light by the luciferase-catalyzed bioluminescence reaction. Because of its cascade signal amplification feature, d-Luc@CHA displayed a remarkable "turn-on" response (248-fold) to 5 µg/mL Hyal-1 with a detection limit of 0.07 ng/mL. Importantly, bioluminescence imaging results validated that d-Luc@CHA could be competent for dynamically visualizing endogenous Hyal-1 changes in living cells and animals and possessed the capability of discriminating between normal and cancer cells, thus offering a promising toolbox to evaluate Hyal-1 roles in biological processes as well as to diagnose Hyal-1-related diseases.


Assuntos
Luciferina de Vaga-Lumes , Neoplasias , Animais , Hialuronoglucosaminidase , Luciferases/genética , Luciferases de Vaga-Lume
19.
J Cell Mol Med ; 24(9): 4944-4955, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32198976

RESUMO

Bone defects resulting from non-union fractures or tumour resections are common clinical problems. Long non-coding RNAs (lncRNAs) are reported to play vital roles in stem cell differentiation. The aim of this study was to elucidate the role of lncRNA-H19 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Following the establishment of an osteogenic differentiation model in rats, the expression of H19, microRNA-149 (miR-149) and stromal cell-derived factor-1 (SDF-1) was measured by RT-qPCR. Thereafter, BMMSCs were isolated from rats and treated with a series of mimic, inhibitor or siRNA. SDF-1 expression, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content were detected. The mineralized and calcified nodules were assessed by alizarin red S and Von Kossa staining. BMMSC surface markers were detected by flow cytometry. Western blot analysis was used to measure the expression of ALP, OCN, runt-related transcription factor 2 (RUNX2) and osterix (OSX) proteins. Lastly, dual-luciferase reporter gene assay and RNA immunoprecipitation were applied to verify the relationship of H19, miR-149 and SDF-1. Overexpressed H19 and SDF-1 and poorly expressed miR-149 were found in rats with osteogenic differentiation. H19 increased SDF-1 expression by binding to miR-149. H19 enhanced ALP activity, OCN content, calcium deposit and ALP, OCN, RUNX2 and OSX protein expression of BMMSCS by up-regulating SDF-1 via binding to miR-149. Taken together, up-regulated H19 could promote the osteogenic differentiation of BMMSCs by increasing SDF-1 via miR-149.


Assuntos
Células da Medula Óssea/citologia , Quimiocina CXCL12/metabolismo , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/citologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Regeneração Óssea , Diferenciação Celular , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Genes Reporter , Masculino , Osteocalcina/biossíntese , Osteogênese , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , Transfecção , Regulação para Cima
20.
J Plant Physiol ; 246-247: 153137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32112956

RESUMO

NH4+ is not only the primary nitrogen for rice, a well-known NH4+ specialist, but is also the chief limiting factor for its production. Limiting NH4+ triggers a series of physiological and biochemical responses that help rice optimise its nitrogen acquisition. However, the dynamic nature and spatial distribution of the adjustments at the whole plant level during this response are still unknown. Here, nitrogen-starved rice seedlings were treated with 0.1 mM (NH4)2SO4 for 4 or 12 h, and then the shoots and roots were harvested for RNA-Seq analysis. We identified 138 and 815 differentially expressed genes (DEGs) in shoots, and 597 and 1074 in roots following 4 and 12 h treatment, respectively. Up-regulated DEGs mainly participated in phenylpropanoid, sugar, and amino acid metabolism, which was confirmed by chemical content analysis. The transcription factor OsJAZ9 was the most pronouncedly induced component under low NH4+ in roots, and a significant increase in root growth, NH4+ absorption, amino acid, and sugar metabolism in response to resupplied NH4+ following nitrogen starvation was identified in JAZ9ox (OsJAZ9-overexpressed) and coi1 (OsCOI1-RNAi). Our data provide comprehensive insight into the whole-plant transcriptomic response in terms of metabolic processes and signaling transduction to a low-NH4+ signal, and identify the transcription factor OsJAZ9 and its involvement in the regulation of carbon/nitrogen metabolism as central to the response to low NH4+.


Assuntos
Compostos de Amônio/metabolismo , Nitrogênio/metabolismo , Oryza/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Transdução de Sinais , Compostos de Amônio/administração & dosagem , Perfilação da Expressão Gênica , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Fatores de Transcrição
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