Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 97
Filtrar
1.
Plant Cell ; 36(7): 2531-2549, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38526222

RESUMO

Histospecification and morphogenesis of anthers during development in Arabidopsis (Arabidopsis thaliana) are well understood. However, the regulatory mechanism of microsporocyte generation at the pre-meiotic stage remains unclear, especially how archesporial cells are specified and differentiate into 2 cell lineages with distinct developmental fates. SPOROCYTELESS (SPL) is a key reproductive gene that is activated during early anther development and remains active. In this study, we demonstrated that the EAR motif-containing adaptor protein (ECAP) interacts with the Gro/Tup1 family corepressor LEUNIG (LUG) and the BES1/BZR1 HOMOLOG3 (BEH3) transcription factor to form a transcription activator complex, epigenetically regulating SPL transcription. SPL participates in microsporocyte generation by modulating the specification of archesporial cells and the archesporial cell-derived differentiation of somatic and reproductive cell layers. This study illustrates the regulation of SPL expression by the ECAP-LUG-BEH3 complex, which is essential for the generation of microsporocytes. Moreover, our findings identified ECAP as a key transcription regulator that can combine with different partners to regulate gene expression in distinct ways, thereby facilitating diverse processes in various aspects of plant development.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Pólen/genética , Pólen/metabolismo , Pólen/crescimento & desenvolvimento , Proteínas Correpressoras/metabolismo , Proteínas Correpressoras/genética , Proteínas Nucleares
2.
Cell Commun Signal ; 22(1): 301, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822356

RESUMO

BACKGROUND: Intrauterine adhesion (IUA) is one of the most severe causes of infertility in women of childbearing age with injured endometrium secondary to uterine performance. Stem cell therapy is effective in treating damaged endometrium. The current reports mainly focus on the therapeutic effects of stem cells through paracrine or transdifferentiation, respectively. This study investigates whether paracrine or transdifferentiation occurs preferentially in treating IUA. METHODS: Human amniotic mesenchymal stem cells (hAMSCs) and transformed human endometrial stromal cells (THESCs) induced by transforming growth factor beta (TGF-ß1) were co-cultured in vitro. The mRNA and protein expression levels of Fibronectin (FN), Collagen I, Cytokeratin19 (CK19), E-cadherin (E-cad) and Vimentin were detected by Quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and Immunohistochemical staining (IHC). The Sprague-Dawley (SD) rats were used to establish the IUA model. hAMSCs, hAMSCs-conditional medium (hAMSCs-CM), and GFP-labeled hAMSCs were injected into intrauterine, respectively. The fibrotic area of the endometrium was evaluated by Masson staining. The number of endometrium glands was detected by hematoxylin and eosin (H&E). GFP-labeled hAMSCs were traced by immunofluorescence (IF). hAMSCs, combined with PPCNg (hAMSCs/PPCNg), were injected into the vagina, which was compared with intrauterine injection. RESULTS: qPCR and WB revealed that FN and Collagen I levels in IUA-THESCs decreased significantly after co-culturing with hAMSCs. Moreover, CK19, E-cad, and Vimentin expressions in hAMSCs showed no significant difference after co-culture for 2 days. 6 days after co-culture, CK19, E-cad and Vimentin expressions in hAMSCs were significantly changed. Histological assays showed increased endometrial glands and a remarkable decrease in the fibrotic area in the hAMSCs and hAMSCs-CM groups. However, these changes were not statistically different between the two groups. In vivo, fluorescence imaging revealed that GFP-hAMSCs were localized in the endometrial stroma and gradually underwent apoptosis. The effect of hAMSCs by vaginal injection was comparable to that by intrauterine injection assessed by H&E staining, MASSON staining and IHC. CONCLUSIONS: Our data demonstrated that hAMSCs promoted endometrial repair via paracrine, preferentially than transdifferentiation.


IUA is the crucial cause of infertility in women of childbearing age, and no satisfactory treatment measures have been found in the clinic. hAMSCs can effectively treat intrauterine adhesions through paracrine and transdifferentiation mechanisms. This study confirmed in vitro and in vivo that amniotic mesenchymal stem cells preferentially inhibited endometrial fibrosis and promoted epithelial repair through paracrine, thus effectively treating intrauterine adhesions. The level of fibrosis marker proteins in IUA-THESCs decreased significantly after co-culturing with hAMSCs for 2 days in vitro. However, the level of epithelial marker proteins in hAMSCs increased significantly, requiring at least 6 days of co-culture. hAMSCs-CM had the same efficacy as hAMSCs in inhibiting fibrosis and promoting endometrial repair in IUA rats, supporting the idea that hAMSCs promoted endometrial remodeling through paracrine in vivo. In addition, GFP-labeled hAMSCs continuously colonized the endometrial stroma instead of the epithelium and gradually underwent apoptosis. These findings prove that hAMSCs ameliorate endometrial fibrosis of IUA via paracrine, preferentially than transdifferentiation, providing the latest insights into the precision treatment of IUA with hAMSCs and a theoretical basis for promoting the "cell-free therapy" of MSCs.


Assuntos
Âmnio , Transdiferenciação Celular , Endométrio , Células-Tronco Mesenquimais , Comunicação Parácrina , Ratos Sprague-Dawley , Feminino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Humanos , Endométrio/citologia , Endométrio/metabolismo , Animais , Âmnio/citologia , Âmnio/metabolismo , Ratos , Transplante de Células-Tronco Mesenquimais/métodos , Técnicas de Cocultura , Aderências Teciduais/patologia , Aderências Teciduais/metabolismo
3.
J Chem Inf Model ; 64(7): 2393-2404, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37799091

RESUMO

Antimicrobial peptides (AMPs) are small molecular polypeptides that can be widely used in the prevention and treatment of microbial infections. Although many computational models have been proposed to help identify AMPs, a high-performance and interpretable model is still lacking. In this study, new benchmark data sets are collected and processed, and a stacking deep architecture named AMPpred-MFA is carefully designed to discover and identify AMPs. Multiple features and a multihead attention mechanism are utilized on the basis of a bidirectional long short-term memory (LSTM) network and a convolutional neural network (CNN). The effectiveness of AMPpred-MFA is verified through five independent tests conducted in batches. Experimental results show that AMPpred-MFA achieves a state-of-the-art performance. The visualization interpretability analyses and ablation experiments offer a further understanding of the model behavior and performance, validating the importance of our feature representation and stacking architecture, especially the multihead attention mechanism. Therefore, AMPpred-MFA can be considered a reliable and efficient approach to understanding and predicting AMPs.


Assuntos
Peptídeos Antimicrobianos , Benchmarking , Redes Neurais de Computação
4.
J Pept Sci ; 30(7): e3572, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38396336

RESUMO

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G-25 gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2-induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 µg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries.


Assuntos
Antioxidantes , Peptídeos , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Células HEK293 , Peróxido de Hidrogênio , Hidrólise , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/isolamento & purificação , Alimentos de Soja/análise
5.
J Biochem Mol Toxicol ; 38(4): e23676, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38561971

RESUMO

Although the treatment of ovarian cancer has made great progress, there are still many patients who are not timely detected and given targeted therapy due to unknown pathogenesis. Recent studies have found that hsa_circ_0015326 is upregulated in ovarian cancer and is involved in the proliferation, invasion, and migration of ovarian cancer cells. However, whether hsa_circ_0015326 can be used as a new target of ovarian cancer needs further investigation. Therefore, the effect of hsa_circ_0015326 on epithelial ovarian cancer was investigated in this study. At first, si-hsa_circ_0015326 lentivirus was transfected into epithelial ovarian cancer cells. Then real-time fluorescence quantitative PCR (qRT-PCR) was used to detect hsa_circ_0015326 level. The proliferation of ovarian cancer cells was detected by CCK-8 assay. The horizontal and vertical migration abilities of the cells were detected by wound-healing assay and Transwell assay, respectively. Transwell assay was also used to determine the invasion rate. As for the apoptosis rate, it was assessed by flow cytometry. As a result, the expression level of hsa_circ_0015326 in A2780 and SKOV3 was found to be higher than that in IOSE-80. However, after transfecting si-hsa_circ_0015326 and si-NC into the cells, the proliferation, migration, and invasion abilities of A2780 and SKOV3 cells in the si-hsa_circ_0015326 group were significantly reduced in comparison to those in the si-NC and mock groups, while their apoptosis rates were elevated. Collectively, silencing hsa_circ_0015326 bears the capability of inhibiting the proliferation, migration, and invasion of ovarian cancer cells while increasing apoptosis rate. It can be concluded that hsa_circ_0015326 promotes the malignant biological activities of epithelial ovarian cancer cells.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , RNA/metabolismo , Carcinoma Epitelial do Ovário/genética , RNA Circular/genética , RNA Circular/metabolismo , Linhagem Celular Tumoral , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proliferação de Células , Apoptose , MicroRNAs/metabolismo , Movimento Celular
6.
Environ Res ; 252(Pt 3): 119012, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38704010

RESUMO

Microplastics and heavy metals are ubiquitous and persistent contaminants that are widely distributed worldwide, yet little is known about the effects of their interaction on soil ecosystems. A soil incubation experiment was conducted to investigate the individual and combined effects of polyethylene microplastics (PE-MPs) and lead (Pb) on soil enzymatic activities, microbial biomass, respiration rate, and community diversity. The results indicate that the presence of PE-MPs notably reduced soil pH and elevated soil Pb bioavailability, potentially exacerbated the combined toxicity on the biogeochemical cycles of soil nutrients, microbial biomass carbon and nitrogen, and the activities of soil urease, sucrase, and alkaline phosphatase. Soil CO2 emissions increased by 7.9% with PE-MPs alone, decreased by 46.3% with single Pb, and reduced by 69.4% with PE-MPs and Pb co-exposure, compared to uncontaminated soils. Specifically, the presence of PE-MPs and Pb, individually and in combination, facilitated the soil metabolic quotient, leading to reduced microbial metabolic efficiency. Moreover, the addition of Pb and PE-MPs modified the composition of the microbial community, leading to the enrichment of specific taxa. Tax4Fun analysis showed the effects of Pb, PE-MPs and their combination on the biogeochemical processes and ecological functions of microbes were mainly by altering amino acid metabolism, carbohydrate metabolism, membrane transport, and signal transduction. These findings offer valuable insights into the ecotoxicological effects of combined PE-MPs and Pb on soil microbial dynamics, reveals key assembly mechanisms and environmental drivers, and highlights the potential threat of MPs and heavy metals to the multifunctionality of soil ecosystems.


Assuntos
Biomassa , Chumbo , Microplásticos , Polietileno , Microbiologia do Solo , Poluentes do Solo , Chumbo/toxicidade , Poluentes do Solo/toxicidade , Microplásticos/toxicidade , Polietileno/toxicidade , Solo/química , Ecotoxicologia
7.
Small ; 19(27): e2300207, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36978231

RESUMO

Allostery is a naturally occurring mechanism in which effector binding induces the modulation and fine control of a related biomolecule function. Deoxyribozyme (DNAzyme) with catalytic activity and substrate recognition ability is ideal to be regulated by allosteric strategies. However, the current regulations frequently confront various obstacles, such as severe activity decay, signal leakage, and limited effectors. In this work, a rational regulation strategy for developing versatile effectors-responsive allosteric nucleic acid enzyme (ANAzyme) by introducing an allosteric domain in response to diverse effectors is established. The enzyme-like activity of this re-engineered ANAzyme can be modulated in a more predictable and fine way compared with the previous DNAzyme regulation strategies. Based on the allosteric strategy, the construction of allosterically coregulatory nanodevices and a series of basic logic gates and logic circuits are achieved, demonstrating that the proposed ANAzyme-regulated strategy showed great potential in molecular computing. Given these facts, the rational design of ANAzyme with the allosteric domain presented here can expand the available toolbox to develop a variety of stimuli-responsive allosteric DNA materials, including molecular machines, computing systems, biosensing platforms, and gene-silencing tools.


Assuntos
DNA Catalítico , DNA Catalítico/metabolismo , DNA , Lógica
8.
Cell Biol Int ; 47(1): 75-85, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36317446

RESUMO

Human amniotic transplantation has been proposed to improve the therapeutic efficacy of intrauterine adhesions (IUAs). Human amniotic mesenchymal stem stromal cells (hAMSCs) can differentiate into multiple tissue types. This study aimed to investigate the mechanism by which hAMSCs transplantation promotes endometrial regeneration. The rat models with IUA were established through mechanical and infective methods, and PKH26-labeled hAMSCs were transplanted through the tail vein (combined with/without estrogen). Under three different conditions, hAMSCs differentiated into endometrium-like cells. HE and Mason staining assays, and immunohistochemistry were used to compare the changes in rat models treated with hAMSCs and/or estrogen transplantation. To define the induction of hAMSCs to endometrium-like cells in vitro, an induction medium (cytokines, estrogen) was used to investigate the differentiation of hAMSCs into endometrium-like cells. qRT-polymerase chain reaction (PCR) and western blotting were performed to detect the differentiation of hAMSCs into endometrium-like cells. A greater number of glands, fewer endometrial fibrotic areas, and stronger expression of vascular endothelial growth factor and cytokeratin in the combined group (hAMSCs transplantation combined with estrogen) than in the other treatment groups were observed. hAMSCs could be induced into endometrium-like cells by cytokine treatment (TGF-ß1, EGF, and PDGF-BB). Transplantation of hAMSCs is an effective alternative for endometrial regeneration after injury in rats. The differentiation protocol for hAMSCs will be useful for further studies on human endometrial regeneration.


Assuntos
Endométrio , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Regeneração , Doenças Uterinas , Animais , Feminino , Humanos , Ratos , Endométrio/fisiologia , Estrogênios/metabolismo , Células-Tronco Mesenquimais/fisiologia , Aderências Teciduais/cirurgia , Aderências Teciduais/terapia , Doenças Uterinas/cirurgia , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
J Biochem Mol Toxicol ; 37(9): e23419, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37341014

RESUMO

In the context of diabetes mellitus (DM), the circulating cathepsin S (CTSS) level is significantly higher in the cardiovascular disease group. Therefore, this study was designed to investigate the role of CTSS in restenosis following carotid injury in diabetic rats. To induce DM, 60 mg/kg of streptozotocin (STZ) in citrate buffer was injected intraperitoneally into Sprague-Dawley rats. After successful modeling of DM, wire injury of the rat carotid artery was performed, followed by adenovirus transduction. Levels of blood glucose and Th17 cell surface antigens including ROR-γt, IL-17A, IL-17F, IL-22, and IL-23 in perivascular adipose tissues (PVAT) were evaluated. For in vitro analysis, human dendritic cells (DCs) were treated with 5.6-25 mM glucose for 24 h. The morphology of DCs was observed using an optical microscope. CD4+ T cells derived from human peripheral blood mononuclear cells were cocultured with DCs for 5 days. Levels of IL-6, CTSS, ROR-γt, IL-17A, IL-17F, IL-22 and IL-23 were measured. Flow cytometry was conducted to detect DC surface biomarkers (CD1a, CD83, and CD86) and Th17 cell differentiation. The collected DCs presented a treelike shape and were positive for CD1a, CD83, and CD86. Glucose impaired DC viability at the dose of 35 mM. Glucose treatment led to an increase in CTSS and IL-6 expression in DCs. Glucose-treated DCs promoted the differentiation of Th17 cells. CTSS depletion downregulated IL-6 expression and inhibited Th17 cell differentiation in vitro and in vivo. CTSS inhibition in DCs inhibits Th17 cell differentiation in PVAT tissues from diabetic rats following vascular injury.


Assuntos
Diabetes Mellitus Experimental , Lesões do Sistema Vascular , Ratos , Humanos , Animais , Interleucina-17 , Células Th17/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Diabetes Mellitus Experimental/metabolismo , Lesões do Sistema Vascular/metabolismo , Ratos Sprague-Dawley , Diferenciação Celular , Células Dendríticas/metabolismo , Interleucina-23/metabolismo , Glucose/metabolismo
10.
Eur Arch Otorhinolaryngol ; 280(2): 861-867, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36153784

RESUMO

PURPOSE: To investigate the clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal RDD. METHODS: A retrospective analysis was performed on 16 patients who were initially diagnosed and treated with otolaryngological extranodal RDD in our hospital from January 2013 to January 2019. RESULTS: There were 9 females and 7 males. The mean diagnostic age was 45.35. Nasal, laryngeal and otic RDD were, respectively, accounting for 56.25%, 31.25% and 12.5%. The median interval diagnostic time was individually 1, 0.5 and 0.2 year for nasal, laryngeal and otic RDD. The most common symptoms were separately progressive nasal congestion, dyspnea, otorrhea in nasal, laryngeal and otic RDD. 13 had cervical lymph node swelling on MRI. Surgery or postoperative radiotherapy were conformed. In the end, 14 patients with RDD survived. The survival rate is as high as 87.5%. One of them died of RDD in the fifth year. One case was lost to follow-up 2 years after treatment. Patients survive for at least 2 years and up to 9 years. There was no significant difference in life expectancy of extranodal RDD among different parts of ENT (P = 0.508 > 0.05). The average ages of laryngeal and nasal RDD were similar (P = 0.898 > 0.05). However, the age of both was significantly higher than ear RDD (P = 0.023 and 0.019 < 0.05). CONCLUSIONS: The average diagnostic age was more than 20 years. Nasal RDD was the most common in this area. All laryngeal RDD had infiltrated subglottis. Functional surgery and postoperative radiotherapy can be used to achieve long-term remission and survival.


Assuntos
Histiocitose Sinusal , Laringe , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Histiocitose Sinusal/complicações , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/terapia , Laringe/patologia , Imageamento por Ressonância Magnética , Prognóstico , Estudos Retrospectivos
11.
Int J Mol Sci ; 24(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38003605

RESUMO

Anthocyanin accumulation in plants plays important roles in plant growth and development, as well as the response to environmental stresses. Anthocyanins have antioxidant properties and play an important role in maintaining the reactive oxygen species (ROS) homeostasis in plant cells. Furthermore, anthocyanins also act as a "sunscreen", reducing the damage caused by ultraviolet radiation under high-light conditions. The biosynthesis of anthocyanin in plants is mainly regulated by an MYB-bHLH-WD40 (MBW) complex. In recent years, many new regulators in different signals involved in anthocyanin biosynthesis were identified. This review focuses on the regulation network mediated by different environmental factors (such as light, salinity, drought, and cold stresses) and phytohormones (such as jasmonate, abscisic acid, salicylic acid, ethylene, brassinosteroid, strigolactone, cytokinin, and auxin). We also discuss the potential application value of anthocyanin in agriculture, horticulture, and the food industry.


Assuntos
Antocianinas , Reguladores de Crescimento de Plantas , Raios Ultravioleta , Plantas , Ácido Abscísico , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética
12.
New Phytol ; 233(5): 2216-2231, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34942029

RESUMO

Anthocyanins are a subgroup of plant flavonoids with antioxidant activities and are often induced by various biotic and abiotic stresses in plants, probably to efficiently scavenge free radicals and reactive oxygen species. However, the regulatory mechanisms of salt stress-induced anthocyanin biosynthesis remain unclear. Using molecular and genetic techniques we demonstrated key roles of ECAP in differential salt-responsive anthocyanin biosynthesis pathways in Arabidopsis thaliana. ECAP, JAZ6/8 and TPR2 are known to form a transcriptional repressor complex, and negatively regulate jasmonate (JA)-responsive anthocyanin accumulation. In this study, we demonstrated that under moderate salt stress, the accumulation of anthocyanins is partially dependent on JA signaling, which degrades JAZ proteins but not ECAP. More interestingly, we found that high salinity rather than moderate salinity induces the degradation of ECAP through the 26S proteasome pathway, and this process is independent of JA signaling. Further analysis revealed that ECAP interacts with MYB75 (a transcription factor activating anthocyanin biosynthetic genes) and represses its transcriptional activity in the absence of high salinity. Our results indicated that plants adopt different strategies for fine-tuning anthocyanin accumulation under different levels of salt stress, and further elucidated the complex regulation of anthocyanin biosynthesis during plant development and responses to environmental stresses.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Antocianinas/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Salino , Fatores de Transcrição/metabolismo
13.
Proc Natl Acad Sci U S A ; 116(28): 14349-14357, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31239335

RESUMO

Endocytosis is essential to all eukaryotes, but how cargoes are selected for internalization remains poorly characterized. Extracellular cargoes are thought to be selected by transmembrane receptors that bind intracellular adaptors proteins to initiate endocytosis. Here, we report a mechanism for clathrin-mediated endocytosis (CME) of extracellular lanthanum [La(III)] cargoes, which requires extracellular arabinogalactan proteins (AGPs) that are anchored on the outer face of the plasma membrane. AGPs were colocalized with La(III) on the cell surface and in La(III)-induced endocytic vesicles in Arabidopsis leaf cells. Superresolution imaging showed that La(III) triggered AGP movement across the plasma membrane. AGPs were then colocalized and physically associated with the µ subunit of the intracellular adaptor protein 2 (AP2) complexes. The AGP-AP2 interaction was independent of CME, whereas AGP's internalization required CME and AP2. Moreover, we show that AGP-dependent endocytosis in the presence of La(III) also occurred in human cells. These findings indicate that extracellular AGPs act as conserved CME cargo receptors, thus challenging the current paradigm about endocytosis of extracellular cargoes.


Assuntos
Endocitose/genética , Galactanos/metabolismo , Lantânio/farmacologia , Metais Terras Raras/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Membrana Celular/efeitos dos fármacos , Clatrina/química , Endocitose/efeitos dos fármacos , Galactanos/genética , Humanos , Lantânio/química , Lantânio/metabolismo , Metais Terras Raras/química , Metais Terras Raras/metabolismo , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo
14.
Ecotoxicol Environ Saf ; 234: 113389, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35272194

RESUMO

Soils co-contaminated with polycyclic aromatic hydrocarbons (PAHs) and cadmium (Cd) have serious environmental impacts and are highly toxic to humans and ecosystems. Phytoremediation is an effective biotechnology for the remediation and restoration of PAH- and Cd-polluted soils. Pot experiments were conducted to investigate the individual and combined effects of PAHs (1238.62 mg kg-1) and Cd (23.1 mg kg-1) on the phytoremediation potential of Bermuda grass grown in contaminated soils. Bermuda grass exhibited a significant decrease in plant growth rate, leaf pigment content, root activity, plant height and biomass and a remarkable increase in malondialdehyde content and electrolyte leakage when grown in PAH- and Cd-contaminated soils compared with grass grown in uncontaminated soils. The activity of soil enzymes, including urease, alkaline phosphatase, sucrose, and fluorescein diacetate hydrolysis, were reduced in soil with PAH and Cd stress. Furthermore, the toxicity of combined PAHs and Cd on Bermuda grass growth and soil enzyme activity was much higher than that of PAH or Cd stress alone, suggesting a synergistic effect of PAHs and Cd on cytotoxicity. To scavenge redundant reactive oxygen species and avoid oxidative damage, Bermuda grass increased plant catalase, superoxide dismutase, and peroxidase activity and soluble sugar and proline content. The bioconcentration factor of Cd in Bermuda grass grown under Cd alone and combined PAH and Cd exposure was greater than 1 for both, suggesting that Bermuda grass has a high Cd accumulation ability. Under PAH alone and combined PAH and Cd exposure conditions, a higher PAH removal rate (41.5-56.8%) was observed in soils planted with Bermuda grass than in unplanted soils (24.8-29.8%), indicating that Bermuda grass has a great ability to degrade PAHs. Bermuda grass showed great phytoremediation potential for the degradation of PAHs and phytoextraction of Cd in co-contaminated soils.

15.
Pharm Dev Technol ; 27(6): 695-701, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35899462

RESUMO

The aim of this study was to develop a gambogic acid-loaded mixed micelles (GA-M) system, using Kolliphor HS15 and lecithin, for enhancement of oral bioavailability. GA-M was prepared using the thin film hydration method, and particle size and zeta potential indexes were used to determine the optimized formulation was optimized with taking particle size, zeta potential as indexes. The optimal GA-M system had a mean particle size in the nanometer range (87.22 ± 0.68 nm) and zeta potential greater than 20 mV in magnitude (-21.63 ± 1.69 mV) at a 1:1 proportion of HS15: lecithin. Additionally, the carriers had a high entrapment efficiency (98.32 ± 3.52%) and drug loading (4.68 ± 0.17%). Furthermore, the in vitro GA release characteristics followed first-order kinetics, suggesting that the release of the molecule was achieved both by medium diffusion and structural erosion. Transport elucidation in Caco-2 cells demonstrated that the efflux ratio of encapsulated GA was dramatically decreased from 1.42 to 0.76, and pharmacokinetic studies showed that the oral bioavailability of GA-M was 2.3 times higher than that of free GA, indicating that HS15/lecithin mixed micelles could promote absorption in the gastrointestinal tract. Overall, these results present a micelle system suitable for oral delivery, with increased solubility and oral bioavailability of GA.


Assuntos
Lecitinas , Micelas , Administração Oral , Disponibilidade Biológica , Células CACO-2 , Portadores de Fármacos/química , Humanos , Tamanho da Partícula , Solubilidade , Xantonas
16.
J Cell Mol Med ; 25(23): 11002-11015, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34724320

RESUMO

Intrauterine adhesions (IUAs) severely hamper women's reproductive functions. Human amniotic mesenchymal stromal cell (hAMSC) transplantation is effective in treating IUAs. Here, we examined the function of Notch signalling in IUA treatment with hAMSC transplantation. Forty-five Sprague-Dawley female rats were randomly divided into the sham operation, IUA, IUA + E2, IUA + hAMSCs and IUA + hAMSCs + E2 groups. After IUA induction in the rats, hAMSCs promoted endometrial regeneration and repair via differentiation into endometrial epithelial cells. In all groups, the expression of key proteins in Notch signalling was detected in the uterus by immunohistochemistry. The results indicated Notch signalling activation in the hAMSCs and hAMSCs + E2 groups. We could also induce hAMSC differentiation to generate endometrial epithelial cells in vitro. Furthermore, the inhibition of Notch signalling using the AdR-dnNotch1 vector suppressed hAMSC differentiation (assessed by epithelial and mesenchymal marker levels), whereas its activation using the AdR-Jagged1 vector increased differentiation. The above findings indicate Notch signalling mediates the differentiation of hAMSCs into endometrial epithelial cells, thus promoting endometrial regeneration and repair; Notch signalling could have an important function in IUA treatment.


Assuntos
Âmnio/metabolismo , Endométrio/metabolismo , Células-Tronco Mesenquimais/metabolismo , Receptores Notch/metabolismo , Regeneração/fisiologia , Transdução de Sinais/fisiologia , Aderências Teciduais/metabolismo , Âmnio/fisiologia , Animais , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Endométrio/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Ratos , Ratos Sprague-Dawley , Aderências Teciduais/fisiopatologia , Doenças Uterinas/metabolismo , Doenças Uterinas/fisiopatologia , Útero/metabolismo , Útero/fisiologia
18.
Environ Monit Assess ; 191(2): 90, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30666420

RESUMO

Reducing agricultural greenhouse gas (GHG) emissions is attracting increasing attention. Balanced fertilization (BF) of cropland has been widely promoted and applied and has great potential to reduce GHG emissions. This study assesses GHG mitigation of BF cropland systems including winter wheat and summer maize double-cropping system (wheat-maize) and winter oilseed rape (Brassica napus) and rice double-cropping system (rape-rice) in Shaanxi province, China. We determined the boundaries, scenarios, leakage, and sources of GHG mitigation and developed a measurement system for GHG mitigation under these cropping systems for BF farmland. In the measurement system, except for the changes in nitrogen fertilizer rates, soil carbon storage, mechanical fuel consumption, and fertilizer management mode (paddy), change in crop yield was recommended as a primary source of GHG mitigation. The BF cropland areas of wheat-maize and rape-rice were 2818.89 ha and 1671.73 ha, respectively. The use of BF reduced the GHG emissions of wheat-maize by 1.15 tCO2 equivalent (CO2e) ha-1 per year and the emissions of rape-rice by 1.05 tCO2e ha-1 per year. The BF cropland produced 5007.6 tCO2e per year. Our results do not only provide a reference for the assessment of GHG mitigation on BF cropland under double-cropping systems, but also will be helpful for improving the methodology of GHG mitigation on BF cropland.


Assuntos
Produção Agrícola/métodos , Produtos Agrícolas/crescimento & desenvolvimento , Monitoramento Ambiental/métodos , Fertilizantes/análise , Efeito Estufa/prevenção & controle , Gases de Efeito Estufa/análise , China , Fazendas , Estações do Ano , Solo/química
20.
ORL J Otorhinolaryngol Relat Spec ; 80(5-6): 307-316, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30205367

RESUMO

AIMS: To confirm the efficacy of conservative treatment for laryngeal contact granuloma and identify factors influencing treatment outcome. METHODS: In this prospective study, patients with laryngeal contact granuloma were divided into a group receiving conservative treatment and a group undergoing surgery. Efficacy was assessed by analyzing the complete response after a 48-week follow-up. The association of treatment outcome with clinical factors was then evaluated. RESULTS: In total, 61 patients, 43 in the group receiving conservative treatment and 18 in the group undergoing surgery, were analyzed, and the complete response rate was 72.1% and 38.9%, respectively. Both univariate analysis and multivariate analysis revealed that treatment modality (p1 = 0.015, p2 = 0.043), voice abuse (p1 = 0.010, p2 = 0.010), and the size of the granuloma (p1 = 0.031, p2 = 0.020) were significantly associated with the complete response of laryngeal contact granuloma. Kaplan-Meier curves showed that alcohol consumption (p = 0.031), voice abuse (p < 0.001), and granuloma size (p = 0.025) were significantly related to the complete response of conservative treatment. CONCLUSIONS: This prospective study strengthens the argument for conservative treatment (instead of surgery) as the first choice for laryngeal contact granuloma. The results also suggest that voice abuse, alcohol consumption, and the size of the granuloma may predict treatment outcome.


Assuntos
Tratamento Conservador , Medicamentos de Ervas Chinesas/uso terapêutico , Granuloma Laríngeo/cirurgia , Granuloma Laríngeo/terapia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Análise de Variância , Feminino , Granuloma Laríngeo/patologia , Humanos , Estimativa de Kaplan-Meier , Laringoscopia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Voz/fisiologia
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa