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1.
Plant Biotechnol J ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861663

RESUMO

The length of hypocotyl affects the height of soybean and lodging resistance, thus determining the final grain yield. However, research on soybean hypocotyl length is scarce, and the regulatory mechanisms are not fully understood. Here, we identified a module controlling the transport of sucrose, where sucrose acts as a messenger moved from cotyledon to hypocotyl, regulating hypocotyl elongation. This module comprises four key genes, namely MYB33, SWEET11, SWEET21 and GA2ox8c in soybean. In cotyledon, MYB33 is responsive to sucrose and promotes the expression of SWEET11 and SWEET21, thereby facilitating sucrose transport from the cotyledon to the hypocotyl. Subsequently, sucrose transported from the cotyledon up-regulates the expression of GA2ox8c in the hypocotyl, which ultimately affects the length of the hypocotyl. During the domestication and improvement of soybean, an allele of MYB33 with enhanced abilities to promote SWEET11 and SWEET21 has gradually become enriched in landraces and cultivated varieties, SWEET11 and SWEET21 exhibit high conservation and have undergone a strong purified selection and GA2ox8c is under a strong artificial selection. Our findings identify a new molecular pathway in controlling soybean hypocotyl elongation and provide new insights into the molecular mechanism of sugar transport in soybean.

2.
Plant Cell ; 33(4): 1196-1211, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-33604650

RESUMO

Arabidopsis thaliana CONSTANS (CO) is an essential transcription factor that promotes flowering by activating the expression of the floral integrator FLOWERING LOCUS T (FT). A number of histone modification enzymes involved in the regulation of flowering have been identified, but the involvement of epigenetic mechanisms in the regulation of the core flowering regulator CO remains unclear. Previous studies have indicated that the transcription factors, FLOWERING BHLH1 (FBH1), FBH2, FBH3, and FBH4, function redundantly to activate the expression of CO. In this study, we found that the KDM3 group H3K9 demethylase JMJ28 interacts with the FBH transcription factors to activate CO by removing the repressive mark H3K9me2. The occupancy of JMJ28 on the CO locus is decreased in the fbh quadruple mutant, suggesting that the binding of JMJ28 is dependent on FBHs. Furthermore, genome-wide occupancy profile analyses indicate that the binding of JMJ28 to the genome overlaps with that of FBH3, indicating a functional association of JMJ28 and FBH3. Together, these results indicate that Arabidopsis JMJ28 functions as a CO activator by interacting with the FBH transcription factors to remove H3K9me2 from the CO locus.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas de Ligação a DNA/metabolismo , Flores/fisiologia , Histona Desmetilases/metabolismo , Fatores de Transcrição/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Histona Desmetilases/genética , Histonas/metabolismo , Lisina/metabolismo , Plantas Geneticamente Modificadas/genética , Fatores de Transcrição/genética
3.
Brain Behav Immun ; 119: 56-83, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38555992

RESUMO

Decreased hippocampal tropomyosin receptor kinase B (TrkB) level is implicated in the pathophysiology of stress-induced mood disorder and cognitive decline. However, how TrkB is modified and mediates behavioral responses to chronic stress remains largely unknown. Here the effects and mechanisms of TrkB cleavage by asparagine endopeptidase (AEP) were examined on a preclinical murine model of chronic restraint stress (CRS)-induced depression. CRS activated IL-1ß-C/EBPß-AEP pathway in mice hippocampus, accompanied by elevated TrkB 1-486 fragment generated by AEP. Specifi.c overexpression or suppression of AEP-TrkB axis in hippocampal CaMKIIα-positive cells aggravated or relieved depressive-like behaviors, respectively. Mechanistically, in addition to facilitating AMPARs internalization, TrkB 1-486 interacted with peroxisome proliferator-activated receptor-δ (PPAR-δ) and sequestered it in cytoplasm, repressing PPAR-δ-mediated transactivation and mitochondrial function. Moreover, co-administration of 7,8-dihydroxyflavone and a peptide disrupting the binding of TrkB 1-486 with PPAR-δ attenuated depression-like symptoms not only in CRS animals, but also in Alzheimer's disease and aged mice. These findings reveal a novel role for TrkB cleavage in promoting depressive-like phenotype.


Assuntos
Depressão , Hipocampo , Estresse Psicológico , Animais , Hipocampo/metabolismo , Camundongos , Depressão/metabolismo , Masculino , Estresse Psicológico/metabolismo , Receptor trkB/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Comportamento Animal/fisiologia , Transdução de Sinais/fisiologia , Doença de Alzheimer/metabolismo , Glicoproteínas de Membrana/metabolismo
4.
Mol Pharm ; 21(6): 2970-2980, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38742943

RESUMO

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.


Assuntos
Doxorrubicina , Nanopartículas , Polietilenoglicóis , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/análogos & derivados , Animais , Nanopartículas/química , Polietilenoglicóis/química , Camundongos , Lipossomos/química , Soroalbumina Bovina/química , Soroalbumina Bovina/administração & dosagem , Distribuição Tecidual , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Fígado/efeitos dos fármacos , Fígado/metabolismo , Tamanho da Partícula , Nanomedicina/métodos , Humanos , Masculino , Feminino
5.
Mol Pharm ; 21(5): 2394-2405, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38647653

RESUMO

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.


Assuntos
Cálcio , Doxorrubicina , Liberação Controlada de Fármacos , Glutationa , Lipossomos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Animais , Camundongos , Lipossomos/química , Humanos , Cálcio/química , Cálcio/metabolismo , Glutationa/química , Feminino , Géis/química , Gelatina/química , Camundongos Nus , Nanopartículas/química , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Reagentes de Ligações Cruzadas/química , Sistemas de Liberação de Medicamentos/métodos
6.
Mol Breed ; 44(2): 16, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38371442

RESUMO

WNK kinases are a unique class of serine/threonine protein kinases that lack a conserved catalytic lysine residue in the kinase domain, hence the name WNK (with no K, i.e., lysine). WNK kinases are involved in various physiological processes in plants, such as circadian rhythm, flowering time, and stress responses. In this study, we identified 26 WNK genes in soybean and analyzed their phylogenetic relationships, gene structures, chromosomal distribution, cis-regulatory elements, expression patterns, and conserved protein motifs. The soybean WNK genes were unevenly distributed on 15 chromosomes and underwent 21 segmental duplication events during evolution. We detected 14 types of cis-regulatory elements in the promoters of the WNK genes, indicating their potential involvement in different signaling pathways. The transcriptome database revealed tissue-specific and salt stress-responsive expression of WNK genes in soybean, the second of which was confirmed by salt treatments and qRT-PCR analysis. We found that most WNK genes were significantly up-regulated by salt stress within 3 h in both roots and leaves, except for WNK5, which showed a distinct expression pattern. Our findings provide valuable insights into the molecular characteristics and evolutionary history of the soybean WNK gene family and lay a foundation for further analysis of WNK gene functions in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01440-5.

7.
J Environ Manage ; 359: 120951, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38669877

RESUMO

Atrazine, a widely used herbicide in modern agriculture, can lead to soil contamination and adverse effects on specific crops. To address this, we investigated the efficacy of biochar loaded with Paenarthrobacter sp. AT5 (an atrazine-degrading bacterial strain) in mitigating atrazine's impact on soybeans in black soil. Bacterially loaded biochar (BBC) significantly enhanced atrazine removal rates in both unplanted and planted soil systems. Moreover, BBC application improved soybean biomass, photosynthetic pigments, and antioxidant systems while mitigating alterations in metabolite pathways induced by atrazine exposure. These findings demonstrate the effectiveness of BBC in reducing atrazine-induced oxidative stress on soybeans in black soil, highlighting its potential for sustainable agriculture.


Assuntos
Atrazina , Carvão Vegetal , Glycine max , Estresse Oxidativo , Poluentes do Solo , Solo , Atrazina/toxicidade , Glycine max/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Solo/química , Carvão Vegetal/química , Poluentes do Solo/toxicidade , Poluentes do Solo/metabolismo , Herbicidas/toxicidade
8.
New Phytol ; 238(4): 1671-1684, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36811193

RESUMO

Soybean (Glycine max) is a major source of protein and edible oil world-wide and is cultivated in a wide range of latitudes. However, it is extremely sensitive to photoperiod, which influences flowering time, maturity, and yield, and severely limits soybean latitude adaptation. In this study, a genome-wide association study (GWAS) identified a novel locus in accessions harboring the E1 allele, called Time of flowering 8 (Tof8), which promotes flowering and enhances adaptation to high latitude in cultivated soybean. Gene functional analyses showed that Tof8 is an ortholog of Arabidopsis FKF1. We identified two FKF1 homologs in the soybean genome. Both FKF1 homologs are genetically dependent on E1 by binding to E1 promoter to activate E1 transcription, thus repressing FLOWERING LOCUS T 2a (FT2a) and FT5a transcription, which modulate flowering and maturity through the E1 pathway. We also demonstrate that the natural allele FKF1bH3 facilitated adaptation of soybean to high-latitude environments and was selected during domestication and improvement, leading to its rapid expansion in cultivated soybean. These findings provide novel insights into the roles of FKF1 in controlling flowering time and maturity in soybean and offer new means to fine-tune adaptation to high latitudes and increase grain yield.


Assuntos
Glycine max , Proteínas de Plantas , Aclimatação , Adaptação Fisiológica , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Fotoperíodo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glycine max/metabolismo
9.
Mol Pharm ; 20(11): 5383-5395, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37747899

RESUMO

Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by ionizing radiation and is used as an antitumor adjuvant and cell protector in cancer chemotherapy and radiotherapy. Amifostine is usually injected intravenously before chemotherapy or radiotherapy and has been used in the treatment of head and neck cancer. However, the inconvenient intravenous administration and its toxic side effects such as hypotension have severely limited its further application in clinic. In order to reduce the toxic and side effects, scientists are trying to develop a variety of drug administration methods and are devoted to developing a wide application of amifostine in radiation protection. This paper reviews the research progress of amifostine for radiation protection in recent years, discusses its mechanism of action, clinical application, and other aspects, with focus on summarizing the most widely studied amifostine injection administration and drug delivery systems, and explored the correlation between various administrations and drug efficacies.


Assuntos
Amifostina , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Proteção Radiológica , Protetores contra Radiação , Humanos , Amifostina/farmacologia , Amifostina/uso terapêutico , Protetores contra Radiação/farmacologia , Administração Intravenosa , Adjuvantes Imunológicos
10.
Phys Chem Chem Phys ; 25(17): 12220-12230, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37073883

RESUMO

The catalytic performance of titanosilicates involving hydrogen peroxide (H2O2) as the oxidant is strongly influenced by the solvents. Until now, there is still a lack of a universal principle that can guide the choice of a solvent. Herein, the kinetics of H2O2 activation catalyzed by various titanosilicates in different solvents is investigated, and an isokinetic compensation effect is concluded. This indicates that the solvent participates in the H2O2 activation process for the formation of a Ti-OOH species. Additionally, the results of isotopically labeled infrared spectra preliminarily confirm that the solvent acts as the mediator to promote the proton transfer during the H2O2 activation process. The catalytic activities of a series of TS-1 catalysts toward 1-hexene epoxidation are compared, which include Ti(OSi)3OH species with a range of densities but a constant total Ti content. This reveals that the solvent effect is closely related to the Ti active sites of these TS-1 catalysts. Based on these results, a principle for the rational choice of solvent for this catalytic process is proposed. ROH is found to be the mediator for Ti(OSi)4 sites, and methanol, which has a strong proton-donating ability, is the best solvent for these sites. However, for the Ti(OSi)3OH sites, water (H2O) is the mediator, and a weaker hydrogen bonding between H2O molecules promotes proton transfer more effectively. The solvent influences the catalytic performance by perturbing the hydrogen bonds between the H2O molecules, and aprotic acetonitrile, which has a strong ability to break the hydrogen bonding network between H2O molecules, is the best solvent for Ti(OSi)3OH sites. This study provides experimental evidence that the solvent promotes the catalytic performance of titanosilicates by assisting the proton transfer during the catalytic H2O2 activation process, which will pave the way toward the rational choice of solvent for the titanosilicate-catalyzed oxidation systems.

11.
Proc Natl Acad Sci U S A ; 117(10): 5260-5268, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32094196

RESUMO

A critical problem in the fight against bacterial infection is the rising rates of resistance and the lack of new antibiotics. The discovery of new targets or new antibacterial mechanisms is a potential solution but is becoming more difficult. Here we report an antibacterial mechanism that safeguards intestine cells from enteropathogenic Escherichia coli (EPEC) by shutting down an infection-responsive signal of the host intestine cell. A key step in EPEC infection of intestinal cells involves Tir-induced actin reorganization. Nck mediates this event by binding with Tir through its SH2 domain (Nck-SH2) and with WIP through its second SH3 domain (Nck-SH3.2). Here we report the design of a synthetic peptide that reacts precisely with a unique cysteine of the Nck-SH3.2 domain, blocks the binding site of the Nck protein, and prevents EPEC infection of Caco-2 cells. Oral update of this nontoxic peptide before EPEC administration safeguards mice from EPEC infection and diarrhea. This study demonstrates domain-specific blockage of an SH3 domain of a multidomain adaptor protein inside cells and the inhibition of Tir-induced rearrangement of the host actin cytoskeleton as a previously unknown antibacterial mechanism.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Peptídeos Catiônicos Antimicrobianos/farmacologia , Escherichia coli Enteropatogênica/efeitos dos fármacos , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/antagonistas & inibidores , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Proteínas Oncogênicas/antagonistas & inibidores , Receptores de Superfície Celular/antagonistas & inibidores , Actinas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Células CACO-2 , Escherichia coli Enteropatogênica/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas/química , Proteínas Oncogênicas/metabolismo , Ligação Proteica , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo , Transdução de Sinais , Domínios de Homologia de src
12.
Int J Mol Sci ; 24(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37108411

RESUMO

Sucrose nonfermenting 2 (Snf2) family proteins are the core component of chromatin remodeling complexes that can alter chromatin structure and nucleosome position by utilizing the energy of ATP, playing a vital role in transcription regulation, DNA replication, and DNA damage repair. Snf2 family proteins have been characterized in various species including plants, and they have been found to regulate development and stress responses in Arabidopsis. Soybean (Glycine max) is an important food and economic crop worldwide, unlike other non-leguminous crops, soybeans can form a symbiotic relationship with rhizobia for biological nitrogen fixation. However, little is known about Snf2 family proteins in soybean. In this study, we identified 66 Snf2 family genes in soybean that could be classified into six groups like Arabidopsis, unevenly distributed on 20 soybean chromosomes. Phylogenetic analysis with Arabidopsis revealed that these 66 Snf2 family genes could be divided into 18 subfamilies. Collinear analysis showed that segmental duplication was the main mechanism for expansion of Snf2 genes rather than tandem repeats. Further evolutionary analysis indicated that the duplicated gene pairs had undergone purifying selection. All Snf2 proteins contained seven domains, and each Snf2 protein had at least one SNF2_N domain and one Helicase_C domain. Promoter analysis revealed that most Snf2 genes had cis-elements associated with jasmonic acid, abscisic acid, and nodule specificity in their promoter regions. Microarray data and real-time quantitative PCR (qPCR) analysis revealed that the expression profiles of most Snf2 family genes were detected in both root and nodule tissues, and some of them were found to be significantly downregulated after rhizobial infection. In this study, we conducted a comprehensive analysis of the soybean Snf2 family genes and demonstrated their responsiveness to Rhizobia infection. This provides insight into the potential roles of Snf2 family genes in soybean symbiotic nodulation.


Assuntos
Arabidopsis , Glycine max , Glycine max/genética , Glycine max/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Família Multigênica
13.
J Exp Bot ; 73(3): 835-847, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-34545936

RESUMO

BRAHMA (BRM) is the ATPase of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodelling complex, which is indispensable for transcriptional inhibition and activation, associated with vegetative and reproductive development in Arabidopsis thaliana. Here, we show that BRM directly binds to the chromatin of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), which integrates multiple flowering signals to regulate floral transition, leading to flowering. In addition, genetic and molecular analysis showed that BRM interacts with GNC (GATA, NITRATE-INDUCIBLE, CARBON METABOLISM INVOLVED), a GATA transcription factor that represses flowering by directly repressing SOC1 expression. Furthermore, BRM is recruited by GNC to directly bind to the chromatin of SOC1. The transcript level of SOC1 is elevated in brm-3, gnc, and brm-3/gnc mutants, which is associated with increased histone H3 lysine 4 tri-methylation (H3K4Me3) but decreased DNA methylation. Taken together, our results indicate that BRM associates with GNC to regulate SOC1 expression and flowering time.


Assuntos
Adenosina Trifosfatases , Proteínas de Arabidopsis , Arabidopsis , Montagem e Desmontagem da Cromatina , Fatores de Transcrição , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição GATA/genética , Fatores de Transcrição GATA/metabolismo , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
Mol Pharm ; 19(5): 1647-1655, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35349292

RESUMO

One of the most significant barriers to the clinical transformation of nanomedicines is low drug distribution in solid tumors due to quick clearance of nanomedicine after injection. Studies have revealed that the distribution of nanomedicine in tumor sites can be considerably improved when the number of nanoparticles supplied in a short period surpasses the threshold. Most routinely employed nanomaterials have dose-related safety concerns. To resolve this problem, we use highly biocompatible albumin to construct blank nanoparticles and doxorubicin loading nanoparticles. Under the guidance of the threshold theory, when the quantity of drug loading nanoparticles is constant, the drug delivery effectiveness improves with the addition of blank nanoparticles. This enhanced impact was verified both in vitro and in vivo. The area under the curve of the high dose group (19.5 × 1011) is 2.5 times higher than that of the low dose group (6.5 × 1011). In addition, the drug distribution of the high dose group at the tumor site was also improved by 1.5 times compared with the low dose group. The results of histopathological sections also showed that the administration of excess blank nanoparticles within 24 h has no damage to the animals. This study contributes to the clinical transition of nanomedicine by providing fresh ideas for anticancer nanomedicine research.


Assuntos
Nanopartículas , Neoplasias , Animais , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Nanomedicina , Neoplasias/tratamento farmacológico , Neoplasias/patologia
15.
Mol Pharm ; 19(3): 819-830, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35170976

RESUMO

The emergence of superbacteria as well as the drug resistance of the current bacteria gives rise to worry regarding a bacterial pandemic and also calls for the development of novel ways to combat the bacteria. Here in this article, we demonstrate that mild hyperthermia induced by hollow mesoporous Prussian blue nanoparticles (HMPBNPs) in alliance with a low concentration of hydrogen peroxide (H2O2) shows a powerful inhibition effect on bacteria. Our results demonstrate that this therapeutic regime could realize almost full growth inhibition of both Gram-positive (Staphylococcus aureus, S. aureus) and -negative bacteria (Escherichia coli, E. coli), as well as potent inhibition/elimination of the S. aureus biofilm. The wound healing results indicate that combination regime of the antibacterial system could be conveniently used for wound disinfection in vivo and could promote wound healing. To our limited knowledge, this is one of the few pioneer works to apply mild hyperthermia for the combat of bacteria, which provides a novel strategy to inspire future studies.


Assuntos
Hipertermia Induzida , Nanopartículas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Escherichia coli , Ferrocianetos , Peróxido de Hidrogênio/farmacologia , Staphylococcus aureus
16.
Pharm Res ; 39(10): 2475-2486, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36008737

RESUMO

Gene therapy is one of the most widely studied treatments and has the potential to treat a variety of intractable diseases. The skin's limited permeability, as the body's initial protective barrier, drastically inhibits the delivery effect of gene medicine. Given the potential adverse effects and physicochemical features of the medications, improving generic drug penetration into the skin barrier and achieving an effective level of target tissues remains a challenge. Microneedles have made tremendous improvements in aided gene transfer and medication delivery as a unique method. Microneedles offer the advantage of being minimally invasive and painless, as well as the ability to distribute gene medicines straight through the stratum corneum. Microneedles have been used to penetrate skin tissue with various nucleic acids and medicines in recent years, allowing for a wide range of applications in the treatment of skin ailments. This review focuses on skin-related disorders and immunity, and it primarily discusses the progress of microneedle transdermal gene therapy in recent years. It also complements the current major vectors and related microneedle gene therapy applications.


Assuntos
Medicamentos Genéricos , Ácidos Nucleicos , Administração Cutânea , Sistemas de Liberação de Medicamentos/métodos , Terapia Genética/métodos , Microinjeções/métodos , Agulhas/efeitos adversos , Preparações Farmacêuticas , Pele
17.
J Sep Sci ; 45(14): 2699-2707, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35544319

RESUMO

This study used capillary electrophoresis with fluorescence detection- and a partial-filling mode-based method for chiral separation of ofloxacin. The deoxyribonucleic acid oligonucleotides with different base sequences were studied as potential chiral selectors including deoxyribonucleic acid tetrahedron, G-quadruplex, and G-riched double-strand deoxyribonucleic acid. Under the optimized conditions, all the deoxyribonucleic acid chiral selectors exhibited excellent chiral separation capabilities with a resolution higher than 1.5. The electrophoretic behavior of the ofloxacin enantiomer might result from the intermediate conjugate with different stabilities between chiral selectors and analytes by a combination of the hydrogen bond and spatial recognition structure. Moreover, satisfactory repeatability regarding run-to-run and interday repeatability was obtained, and all the relative standard deviation values of migration times and resolutions were below 4% (n = 6). Conclusively, both spatial structure and arrangement of the G bases potentiated the chiral separation capability of deoxyribonucleic acid for ofloxacin enantiomer. This work offered a stepping stone for enantioseparation using deoxyribonucleic acid as chiral selectors.


Assuntos
Ofloxacino , Oligonucleotídeos , Eletroforese Capilar/métodos , Estereoisomerismo
18.
Chem Biodivers ; 19(5): e202100951, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35344272

RESUMO

Guava (Psidium guajava L.) leaf essential oil (GLEO) was extracted by water distillation, and its in vitro antioxidant, antidiabetic, and antibacterial properties were evaluated. Using GC/MS to determine the chemical components of GLEO, 27 constituents were identified, accounting for 74.90 % of the total oil content, among which L-caryophyllene (24.46 %), L-calamenene (10.82 %), (-)-globulol (10.69 %), and α-copaene (8.71 %) were the main components. Subsequently, the antioxidant activity of GLEO was determined by DPPH, ABTS, and ß-carotene bleaching tests. The half maximal inhibitory concentration of GLEO for three free radicals were IC50 =17.66±0.07 µg/mL, IC50 =19.28±0.03 µg/mL, and IC50 =3.17±0.01 µg/mL, respectively. Moreover, GLEO exhibited remarkable α-amylase (IC50 =13.99±0.34 µg/mL) and α-glucosidase (IC50 =5.50±1.02 µg/mL) inhibitory activities. It was effective against Streptomyces acidiscabies (MIC=1.25 µg/mL), Ralstonia solanacearum (MIC=5 µg/mL), and Erwinia carotovora subsp carotovora borgey (MIC=2.5 µg/mL), showing significant antibacterial properties. Based on the findings, given the high biological activity of GLEO, it is a biological preservative for food, medicine, and cosmetics and is valuable in natural therapy and crop disease management.


Assuntos
Óleos Voláteis , Psidium , Antibacterianos/análise , Antibacterianos/farmacologia , Antioxidantes/química , Óleos Voláteis/química , Extratos Vegetais/química , Folhas de Planta/química , Psidium/química
19.
Electrophoresis ; 42(11): 1217-1220, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675051

RESUMO

A novel peptide containing antimicrobial sequence and gelatinase cleavage sites was designed for Staphylococcus aureus detection. Since Staphylococcus aureus could secrete gelatinase, the fluorescein labeled peptide GKRWWKWWRRPLGVRGC could be recognized and cleaved. The obtained products were able to be analyzed by capillary electrophoresis with fluorescence detection. To explore the effect of Staphylococcus aureus concentration on enzyme digestion ability of peptide, Staphylococcus aureus with different concentrations were incubated with the peptide. Results indicated that capillary electrophoretic method was efficient for determining Staphylococcus aureus content. Compared with traditional approaches for Staphylococcus aureus detection, capillary electrophoresis possessed higher efficiency, enhanced sensitivity, and low sample consumption. Moreover, the proposed peptide also presented desirable antimicrobial activity. It suggested that the novel antimicrobial peptide used in this research opens a new path of detecting Staphylococcus aureus by capillary electrophoretic method.


Assuntos
Peptídeos Antimicrobianos , Staphylococcus aureus , Sequência de Aminoácidos , Eletroforese Capilar , Fluoresceína , Gelatinases , Staphylococcus aureus/isolamento & purificação
20.
Analyst ; 146(1): 48-63, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33211035

RESUMO

DNA possesses various chemical and physical properties which make it important in biological analysis. The opportunity for DNA to 'meet' capillary-based microsystems is rapidly increasing owing to the expanding development of miniaturization. Novel capillary-based methods can provide favourable platforms for DNA-ligand interaction assay, DNA translocation study, DNA separation, DNA aptamer selection, DNA amplification assay, and DNA digestion. Meanwhile, DNA exhibits great potential in the fabrication of new capillary-based biosensors and enzymatic bioreactors. Moreover, DNA has received significant research interest in improving capillary electrophoresis (CE) performance. We focus on highlighting the advantages of combining DNA and capillary-based microsystems. The general trend presented in this review suggests that the 'meeting' has offered a stepping stone for the application of DNA and capillary-based microsystems in the field of analytical chemistry.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA/genética , Eletroforese Capilar , Miniaturização
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