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1.
Cell ; 172(1-2): 249-261.e12, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29328914

RESUMO

Humans heavily rely on dozens of domesticated plant species that have been further improved through intensive breeding. To evaluate how breeding changed the tomato fruit metabolome, we have generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes from hundreds of tomato genotypes. The combined results illustrate how breeding globally altered fruit metabolite content. Selection for alleles of genes associated with larger fruits altered metabolite profiles as a consequence of linkage with nearby genes. Selection of five major loci reduced the accumulation of anti-nutritional steroidal glycoalkaloids in ripened fruits, rendering the fruit more edible. Breeding for pink tomatoes modified the content of over 100 metabolites. The introgression of resistance genes from wild relatives in cultivars also resulted in major and unexpected metabolic changes. The study reveals a multi-omics view of the metabolic breeding history of tomato, as well as provides insights into metabolome-assisted breeding and plant biology.


Assuntos
Frutas/genética , Metaboloma , Metabolômica/métodos , Melhoramento Vegetal/métodos , Solanum lycopersicum/genética , Flavonoides/genética , Flavonoides/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Seleção Artificial
2.
Small ; 20(27): e2311124, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38258393

RESUMO

The electrochemical nitrogen oxidation reaction (NOR) holds significant potential to revolutionize the traditional nitrate synthesis processes. However, the progression in NOR has been notably stymied due to the sluggish kinetics of initial N2 adsorption and activation processes. Herein, the research embarks on the development of a CeO2-Co3O4 heterostructure, strategically engineered to facilitate the electron transfer from CeO2 to Co3O4. This orchestrated transfer operates to amplify the d-band center of the Co active sites, thereby enhancing N2 adsorption and activation dynamics by strengthening the Co─N bond and diminishing the resilience of the N≡N bond. The synthesized CeO2-Co3O4 manifests promising prospects, showcasing a significant HNO3 yield of 37.96 µg h-1 mgcat -1 and an elevated Faradaic efficiency (FE) of 29.30% in a 0.1 m Na2SO4 solution at 1.81 V versus RHE. Further substantiating these findings, an array of in situ methodologies coupled with DFT calculations vividly illustrate the augmented adsorption and activation of N2 on the surface of CeO2-Co3O4 heterostructure, resulting in a substantial reduction in the energy barrier pertinent to the rate-determining step within the NOR pathway. This research carves a promising pathway to amplify N2 adsorption throughout the electrochemical NOR operations and delineates a blueprint for crafting highly efficient NOR electrocatalysts.

3.
New Phytol ; 242(1): 231-246, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38326943

RESUMO

N6 -methyladenosine (m6 A) is the most abundant mRNA modification in eukaryotes and is an important regulator of gene expression as well as many other critical biological processes. However, the characteristics and functions of m6 A in peanut (Arachis hypogea L.) resistance to bacterial wilt (BW) remain unknown. Here, we analyzed the dynamic of m6 A during infection of resistant (H108) and susceptible (H107) peanut accessions with Ralstonia solanacearum (R. solanacearum), the causative agent of BW. Throughout the transcriptome, we identified 'URUAY' as a highly conserved motif for m6 A in peanut. The majority of differential m6 A located within the 3' untranslated region (UTR) of the transcript, with fewer in the exons. Integrative analysis of RNA-Seq and m6 A methylomes suggests the correlation between m6 A and gene expression in peanut R. solanacearum infection, and functional analysis reveals that m6 A-associated genes were related to plant-pathogen interaction. Our experimental analysis suggests that AhALKBH15 is an m6 A demethylase in peanut, leading to decreased m6 A levels and upregulation of the resistance gene AhCQ2G6Y. The upregulation of AhCQ2G6Y expression appears to promote BW resistance in the H108 accession.


Assuntos
Arachis , Ralstonia solanacearum , Arachis/genética , Transcriptoma , Regulação para Cima , RNA , Doenças das Plantas/genética , Doenças das Plantas/microbiologia
4.
Chemistry ; 30(33): e202400348, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38602023

RESUMO

Utilizing photocatalytic method to produce hydrogen by splitting water is an efficient strategy to solve the hotspot issues of energy crisis and environmental pollution. Herein, we systematically investigate the corresponding properties of the reported Cu-bearing ternary compound monolayer CuP2Se by using the first-principle calculations. The monolayer CuP2Se has quite small cleavage energy of 0.51 J/m2, indicating it can be easily produced by the mechanical exfoliation method experimentally. In addition, it is an indirect bandgap semiconductor material which has a moderate value of 1.91 eV. The conduction band minimum (CBM) and valence band maximum (VBM) can perfectly straddle the redox potentials of water when a biaxial strain of -4% to 4% is applied, unveiling the high photocatalytic thermodynamic stability of monolayer CuP2Se in response to the effect of solvent tension. Remarkably, the monolayer CuP2Se also demonstrates significant sunlight capturing ability in the visible region. The outstanding electronic and optical properties suggest that the monolayer CuP2Se is undoubtedly a viable material for photocatalytic water splitting.

5.
FASEB J ; 37(11): e23241, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37847512

RESUMO

Cementum, a constituent part of periodontal tissues, has important adaptive and reparative functions. It serves to attach the tooth to alveolar bone and acts as a barrier delimit epithelial growth and bacteria evasion. A dynamic and highly responsive cementum is essential for maintaining occlusal relationships and the integrity of the root surface. It is a thin layer of mineralized tissue mainly produced by cementoblasts. Cementoblasts are osteoblast-like cells essential for the restoration of periodontal tissues. In recent years, glucose metabolism has been found to be critical in bone remodeling and osteoblast differentiation. However, the glucose metabolism of cementoblasts remains incompletely understood. First, immunohistochemistry staining and in vivo tracing with 18 F-fluorodeoxyglucose (18 F-FDG) revealed significantly higher glucose metabolism in cementum formation. To test the bioenergetic pathways of cementoblast differentiation, we compared the bioenergetic profiles of mineralized and unmineralized cementoblasts. As a result, we observed a significant increase in the consumption of glucose and production of lactate, coupled with the higher expression of glycolysis-related genes. However, the expression of oxidative phosphorylation-related genes was downregulated. The verified results were consistent with the RNA sequencing results. Likewise, targeted energy metabolomics shows that the levels of glycolytic metabolites were significantly higher in the mineralized cementoblasts. Seahorse assays identified an increase in glycolytic flux and reduced oxygen consumption during cementoblast mineralization. Apart from that, we also found that lactate dehydrogenase A (LDHA), a key glycolysis enzyme, positively regulates the mineralization of cementoblasts. In summary, cementoblasts mainly utilized glycolysis rather than oxidative phosphorylation during the mineralization process.


Assuntos
Cemento Dentário , Ácido Láctico , Diferenciação Celular , Imuno-Histoquímica , Glucose
6.
Cell Commun Signal ; 22(1): 4, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167023

RESUMO

BACKGROUND: Cementoblasts on the tooth-root surface are responsible for cementum formation (cementogenesis) and sensitive to Porphyromonas gingivalis stimulation. We have previously proved transcription factor CXXC-type zinc finger protein 5 (CXXC5) participates in cementogenesis. Here, we aimed to elucidate the mechanism in which CXXC5 regulates P. gingivalis-inhibited cementogenesis from the perspective of mitochondrial biogenesis. METHODS: In vivo, periapical lesions were induced in mouse mandibular first molars by pulp exposure, and P. gingivalis was applied into the root canals. In vitro, a cementoblast cell line (OCCM-30) was induced cementogenesis and submitted for RNA sequencing. These cells were co-cultured with P. gingivalis and examined for osteogenic ability and mitochondrial biogenesis. Cells with stable CXXC5 overexpression were constructed by lentivirus transduction, and PGC-1α (central inducer of mitochondrial biogenesis) was down-regulated by siRNA transfection. RESULTS: Periapical lesions were enlarged, and PGC-1α expression was reduced by P. gingivalis treatment. Upon apical inflammation, Cxxc5 expression decreased with Il-6 upregulation. RNA sequencing showed enhanced expression of osteogenic markers, Cxxc5, and mitochondrial biogenesis markers during cementogenesis. P. gingivalis suppressed osteogenic capacities, mitochondrial biogenesis markers, mitochondrial (mt)DNA copy number, and cellular ATP content of cementoblasts, whereas CXXC5 overexpression rescued these effects. PGC-1α knockdown dramatically impaired cementoblast differentiation, confirming the role of mitochondrial biogenesis on cementogenesis. CONCLUSIONS: CXXC5 is a P. gingivalis-sensitive transcription factor that positively regulates cementogenesis by influencing PGC-1α-dependent mitochondrial biogenesis. Video Abstract.


Assuntos
Cementogênese , Mitocôndrias , Biogênese de Organelas , Animais , Camundongos , Linhagem Celular , Cementogênese/genética , Cementogênese/fisiologia , DNA Mitocondrial/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Fatores de Transcrição/metabolismo , Mitocôndrias/metabolismo
7.
Biomacromolecules ; 25(7): 4177-4191, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38866384

RESUMO

After RNAi was first discovered over 20 years ago, siRNA-based therapeutics are finally becoming reality. However, the delivery of siRNA has remained a challenge. In our previous research, we found that spermine-based poly(ß-amino ester)s are very promising for siRNA delivery. However, the role of hydrophobic modification in siRNA delivery of spermine-based poly(ß-amino ester)s is not fully understood yet. In the current work, we synthesized spermine-based poly(ß-amino ester)s with different percentages of oleylamine side chains, named P(SpOABAE). The chemical structures of the polymers were characterized by 1H NMR. The polymers showed efficient siRNA encapsulation determined by SYBR Gold assays. The hydrodynamic diameters of the P(SpOABAE) polyplexes from charge ratio N/P 1 to 20 were 30-100 nm except for aggregation phenomena observed at N/P 3. Morphology of the polyplexes was visualized by atomic force microscopy, and cellular uptake was determined by flow cytometry in H1299 cells, where all the polyplexes showed significantly higher cellular uptake than hyperbranched polyethylenimine (25 kDa). The most hydrophobic P(SpOABAE) polyplexes were able to achieve more than 90% GFP knockdown in H1299/eGFP cells. The fact that gene silencing efficacy increased with hydrophobicity but cellular uptake was affected by both charge and hydrophobic interactions highlights the importance of endosomal escape. For pulmonary administration and improved storage stability, the polyplexes were spray-dried. Results confirmed the maintained siRNA activity after storage for 3 months at room temperature, indicating potential for dry powder inhalation.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , RNA Interferente Pequeno , Espermina , RNA Interferente Pequeno/química , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/farmacologia , Espermina/química , Humanos , Administração por Inalação , Polímeros/química , Pós/química , Linhagem Celular Tumoral
8.
Inorg Chem ; 63(17): 7886-7895, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38621298

RESUMO

In the quest for proficient electrocatalysts for ammonia's electrocatalytic nitrogen reduction, cobalt oxides, endowed with a rich d-electron reservoir, have emerged as frontrunners. Despite the previously evidenced prowess of CoO in this realm, its ammonia yield witnesses a pronounced decline as the reaction unfolds, a phenomenon linked to the electron attrition from its Co2+ active sites during electrocatalytic nitrogen reduction reaction (ENRR). To counteract this vulnerability, we harnessed electron-laden phosphorus (P) elements as dopants, aiming to recalibrate the electronic equilibrium of the pivotal Co active site, thereby bolstering both its catalytic performance and stability. Our empirical endeavors showcased the doped P-CoO's superior credentials: it delivered an impressive ammonia yield of 49.6 and, notably, a Faradaic efficiency (FE) of 9.6% at -0.2 V versus RHE, markedly eclipsing its undoped counterpart. Probing deeper, a suite of ex-situ techniques, complemented by rigorous theoretical evaluations, was deployed. This dual-pronged analysis unequivocally revealed CoO's propensity for an electron-driven valence metamorphosis to Co3+ post-ENRR. In stark contrast, P-CoO, fortified by P doping, exhibits a discernibly augmented ammonia yield. Crucially, P's intrinsic ability to staunch electron leakage from the active locus during ENRR ensures the preservation of the valence state, culminating in enhanced catalytic dynamism and fortitude. This investigation not only illuminates the intricacies of active site electronic modulation in ENRR but also charts a navigational beacon for further enhancements in this domain.

9.
J Clin Periodontol ; 51(10): 1369-1383, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38956929

RESUMO

AIM: To investigate the relationship and potential causality between biological ageing and periodontitis. MATERIALS AND METHODS: We obtained the National Health and Nutrition Examination Survey (NHANES) and genome-wide association study (GWAS) summary statistics as well as single-cell sequencing data. Multivariate regression analysis based on cross-sectional data, Mendelian randomization (MR) and multi-omics integration analysis were employed to explore the causal association and potential molecular mechanisms between biological ageing and periodontitis. Additionally, two-step MR mediation analysis explored the risk factors in biological ageing-mediated periodontitis. RESULTS: We analysed data from 3189 participants in the NHANES data and found that higher biological age was associated with increased risk of periodontitis. MR analyses revealed causal associations between biological age measures and periodontitis risk. Frailty (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.04-4.18, p = .039) and GrimAge acceleration (OR = 1.16, 95% CI: 1.01-1.32, p = .033) were causally associated with periodontitis risk, and these results were validated in a large-scale meta-periodontitis GWAS dataset. Additionally, the risk effects of body mass index, waist circumference and lifetime smoking on periodontitis were partially mediated by frailty and GrimAge acceleration. CONCLUSIONS: Evidence from cross-sectional survey and MR analysis suggests that biological ageing increases the risk of periodontitis. Additionally, improving the associated risk factors can help prevent both ageing and periodontitis.


Assuntos
Envelhecimento , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Periodontite , Humanos , Estudos Transversais , Periodontite/genética , Feminino , Masculino , Pessoa de Meia-Idade , Envelhecimento/genética , Fatores de Risco , Inquéritos Nutricionais , Idoso , Adulto , Multiômica
10.
J Nanobiotechnology ; 22(1): 193, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643134

RESUMO

Pyroptosis, a novel type of programmed cell death (PCD), which provides a feasible therapeutic option for the treatment of tumors. However, due to the hypermethylation of the promoter, the critical protein Gasdermin E (GSDME) is lacking in the majority of cancer cells, which cannot start the pyroptosis process and leads to dissatisfactory therapeutic effects. Additionally, the quick clearance, systemic side effects, and low concentration at the tumor site of conventional pyroptosis reagents restrict their use in clinical cancer therapy. Here, we described a combination therapy that induces tumor cell pyroptosis via the use of ultrasound-targeted microbubble destruction (UTMD) in combination with DNA demethylation. The combined application of UTMD and hydralazine-loaded nanodroplets (HYD-NDs) can lead to the rapid release of HYD (a demethylation drug), which can cause the up-regulation of GSDME expression, and produce reactive oxygen species (ROS) by UTMD to cleave up-regulated GSDME, thereby inducing pyroptosis. HYD-NDs combined with ultrasound (US) group had the strongest tumor inhibition effect, and the tumor inhibition rate was 87.15% (HYD-NDs group: 51.41 ± 3.61%, NDs + US group: 32.73%±7.72%), indicating that the strategy had a more significant synergistic anti-tumor effect. In addition, as a new drug delivery carrier, HYD-NDs have great biosafety, tumor targeting, and ultrasound imaging performance. According to the results, the combined therapy reasonably regulated the process of tumor cell pyroptosis, which offered a new strategy for optimizing the therapy of GSDME-silenced solid tumors.


Assuntos
Neoplasias , Piroptose , Humanos , Piroptose/fisiologia , Microbolhas , Neoplasias/tratamento farmacológico , Apoptose , Hidralazina/farmacologia , Hidralazina/uso terapêutico
11.
BMC Public Health ; 24(1): 2305, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187832

RESUMO

BACKGROUND: Given the global shifts in environmental conditions and dietary habits, understanding the potential impact of dietary factors and body mass index (BMI) on respiratory diseases, including asthma, is paramount. Investigating these relationships can contribute to the formulation of more effective prevention strategies. The Planetary Health Diet Index (PHDI), a dietary scoring system that balances human health with environmental sustainability, underscores the importance of increasing the consumption of plant-based foods while reducing the intake of red meat, sugar, and highly processed foods. The objective of this study was to assess the association between PHDI and the prevalence of asthma and the mediation effect of BMI in a US general population. METHODS: This study utilized data from 32,388 participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018. Multivariate logistic regression and weighted quantile sum (WQS) regressions were employed to investigate the association between PHDI, individual nutrients, and asthma. Restricted cubic spline (RCS) analysis explored the linear or non-linear relationship between PHDI and asthma. Interaction analyses were conducted on subgroups to validate the findings. Mediation analysis was performed to examine the effect of BMI on the relationship between PHDI and asthma. RESULTS: There was a significant negative association between PHDI and asthma. After adjusting for covariates, for every 10-point increase in PHDI, there was a 4% decrease in the prevalence of asthma (P = 0.025). Moreover, as PHDI increased, there was a trend towards lower asthma prevalence (P for trend < 0.05). WQS analyses showed consistent associations (OR = 0.93, 95%CI: 0.88, 0.98), with Fiber, Vitamin C, and Protein significant factors. The dose-response curve indicated a linear association between PHDI and asthma, with higher PHDI associated with lower asthma prevalence. Additionally, BMI is significantly positively associated with asthma (P < 0.001), and BMI decreases as the PHDI increases (ß = -0.64, P < 0.001). Mediation analysis indicates that BMI significantly mediates the relationship between PHDI and asthma, with a mediation proportion of 33.85% (P < 0.001). CONCLUSION: The results of this study show a strong negative correlation between PHDI and the prevalence of asthma. In addition, BMI mediated this negative relationship.


Assuntos
Asma , Índice de Massa Corporal , Inquéritos Nutricionais , Humanos , Asma/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem , Adolescente , Prevalência , Dieta Saudável/estatística & dados numéricos , Dieta/estatística & dados numéricos , Idoso , Estudos Transversais
12.
Int J Mol Sci ; 25(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38256098

RESUMO

Periodontitis is a chronic infectious disorder damaging periodontal tissues, including the gingiva, periodontal ligament, cementum, and alveolar bone. It arises from the complex interplay between pathogenic oral bacteria and host immune response. Contrary to the previous view of "energy factories", mitochondria have recently been recognized as semi-autonomous organelles that fine-tune cell survival, death, metabolism, and other functions. Under physiological conditions, periodontal tissue cells participate in dynamic processes, including differentiation, mineralization, and regeneration. These fundamental activities depend on properly functioning mitochondria, which play a crucial role through bioenergetics, dynamics, mitophagy, and quality control. However, during the initiation and progression of periodontitis, mitochondrial quality control is compromised due to a range of challenges, such as bacterial-host interactions, inflammation, and oxidative stress. Currently, mounting evidence suggests that mitochondria dysfunction serves as a common pathological mechanism linking periodontitis with systemic conditions like type II diabetes, obesity, and cardiovascular diseases. Therefore, targeting mitochondria to intervene in periodontitis and multiple associated systemic diseases holds great therapeutic potential. This review provides advanced insights into the interplay between mitochondria, periodontitis, and associated systemic diseases. Moreover, we emphasize the significance of diverse therapeutic modulators and signaling pathways that regulate mitochondrial function in periodontal and systemic cells.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Mitocondriais , Periodontite , Humanos , Periodontite/complicações , Inflamação , Periodonto
13.
Int J Mol Sci ; 25(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38396864

RESUMO

Drought stress is a major abiotic factor affecting tomato production and fruit quality. However, the genes and metabolites associated with tomato responses to water deficiency and rehydration are poorly characterized. To identify the functional genes and key metabolic pathways underlying tomato responses to drought stress and recovery, drought-susceptible and drought-tolerant inbred lines underwent transcriptomic and metabolomic analyses. A total of 332 drought-responsive and 491 rehydration-responsive core genes were robustly differentially expressed in both genotypes. The drought-responsive and rehydration-responsive genes were mainly related to photosynthesis-antenna proteins, nitrogen metabolism, plant-pathogen interactions, and the MAPK signaling pathway. Various transcription factors, including homeobox-leucine zipper protein ATHB-12, NAC transcription factor 29, and heat stress transcription factor A-6b-like, may be vital for tomato responses to water status. Moreover, 24,30-dihydroxy-12(13)-enolupinol, caffeoyl hawthorn acid, adenosine 5'-monophosphate, and guanosine were the key metabolites identified in both genotypes under drought and recovery conditions. The combined transcriptomic and metabolomic analysis highlighted the importance of 38 genes involved in metabolic pathways, the biosynthesis of secondary metabolites, the biosynthesis of amino acids, and ABC transporters for tomato responses to water stress. Our results provide valuable clues regarding the molecular basis of drought tolerance and rehydration. The data presented herein may be relevant for genetically improving tomatoes to enhance drought tolerance.


Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Secas , Perfilação da Expressão Gênica/métodos , Transcriptoma , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas
14.
Int J Mol Sci ; 25(13)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39000340

RESUMO

Most α2-AR agonists derived from dexmedetomidine have few structural differences between them and have no selectivity for α2A/2B-AR or Gi/Gs, which can lead to side effects in drugs. To obtain novel and potent α2A-AR agonists, we performed virtual screening for human α2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity. Compound P300-2342 and its three analogs significantly decreased the locomotor activity of mice (p < 0.05). Furthermore, P300-2342 and its three analogs inhibited the binding of [3H] Rauwolscine with IC50 values of 7.72 ± 0.76 and 12.23 ± 0.11 µM, respectively, to α2A-AR and α2B-AR. In α2A-AR-HEK293 cells, P300-2342 decreased forskolin-stimulated cAMP production without increasing cAMP production, which indicated that P300-2342 activated α2A-AR with coupling to the Gαi/o pathway but without Gαs coupling. P300-2342 exhibited no agonist but slight antagonist activities in α2B-AR. Similar results were obtained for the analogs of P300-2342. The docking results showed that P300-2342 formed π-hydrogen bonds with Y394, V114 in α2A-AR, and V93 in α2B-AR. Three analogs of P300-2342 formed several π-hydrogen bonds with V114, Y196, F390 in α2A-AR, and V93 in α2B-AR. We believe that these molecules can serve as leads for the further optimization of α2A-AR agonists with potentially few side effects.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2 , Simulação de Acoplamento Molecular , Receptores Adrenérgicos alfa 2 , Humanos , Animais , Células HEK293 , Receptores Adrenérgicos alfa 2/metabolismo , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Camundongos , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , AMP Cíclico/metabolismo , Masculino , Ligação Proteica
15.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542304

RESUMO

Male sterility is a valuable trait for hybrid seed production in tomato (Solanum lycopersicum). The mutants male sterile-30 (ms-30) and ms-33 of tomato exhibit twisted stamens, exposed stigmas, and complete male sterility, thus holding potential for application in hybrid seed production. In this study, the ms-30 and ms-33 loci were fine-mapped to 53.3 kb and 111.2 kb intervals, respectively. Tomato PISTILLATA (TPI, syn. SlGLO2), a B-class MADS-box transcription factor gene, was identified as the most likely candidate gene for both loci. TPI is also the candidate gene of tomato male sterile mutant 7B-1 and sl-2. Allelism tests revealed that ms-30, ms-33, 7B-1, and sl-2 were allelic. Sequencing analysis showed sequence alterations in the TPI gene in all these mutants, with ms-30 exhibiting a transversion (G to T) that resulted in a missense mutation (S to I); ms-33 showing a transition (A to T) that led to alternative splicing, resulting in a loss of 46 amino acids in protein; and 7B-1 and sl-2 mutants showing the insertion of an approximately 4.8 kb retrotransposon. On the basis of these sequence alterations, a Kompetitive Allele Specific PCR marker, a sequencing marker, and an Insertion/Deletion marker were developed. Phenotypic analysis of the TPI gene-edited mutants and allelism tests indicated that the gene TPI is responsible for ms-30 and its alleles. Transcriptome analysis of ms-30 and quantitative RT-PCR revealed some differentially expressed genes associated with stamen and carpel development. These findings will aid in the marker-assisted selection for ms-30 and its alleles in tomato breeding and support the functional analysis of the TPI gene.


Assuntos
Infertilidade Masculina , Solanum lycopersicum , Humanos , Masculino , Solanum lycopersicum/genética , Alelos , Melhoramento Vegetal , Perfilação da Expressão Gênica , Infertilidade Masculina/genética , Estudos de Associação Genética
16.
Molecules ; 29(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39275053

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly threatening foodborne pathogen capable of causing severe organ and life-threatening diseases. Over the past years, various commercial antibiotics have been used to treat MRSA infections. However, these commercial antibiotics have not yielded efficient results and also cause other side effects; therefore, there is a need for the development of effective alternatives to replace these commercial antibiotics. Suberanilic acid, an amide alkaloid obtained from the endophytic fungus Pestalotiopsis trachycarpicola DCL44, has been identified as a significant antimicrobial agent. However, its antibiotic properties on multi-drug-resistant bacteria such as MRSA have not been fully explored. Therefore, to investigate the potential antimicrobial mechanism of suberanilic acid against MRSA, a quantitative proteomics approach using tandem mass tagging (TMT) was used. The results obtained in the study revealed that suberanilic acid targets multiple pathways in MRSA, including disruption of ribosome synthesis, inhibition of membrane translocation for nutrient uptake (ABC transporter system), and causing dysregulation of carbohydrate and amino acid energy metabolism. These results provide new insights into the mechanism of action of suberanilic acid against MRSA and offer technical support and a theoretical basis for the development of novel food antimicrobial agents derived from endophytic fungal origin.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pestalotiopsis , Endófitos/química , Testes de Sensibilidade Microbiana , Proteômica/métodos
17.
BMC Nurs ; 23(1): 536, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113007

RESUMO

BACKGROUND: This study explored risk perception characteristics and influencing factors among informal caregivers of functionally dependent elderly individuals at home, aiming to improve caregivers' caregiving risk perception and coping abilities and ultimately enhance the quality of life for these individuals. METHODS: We used purposive sampling to select 22 informal caregivers from a community in Zhengzhou City, Henan Province, China, between March and September 2023 and conducted face-to-face semi-structured in-depth interviews. The data were analyzed using Colaizzi's seven-step analysis method. RESULTS: We extracted two themes, caregiving risk perception characteristics and caregiving risk perception associated factors, and eight sub-themes, perceived risk possibility, perceived risk anticipation, perceived severity of consequences, past caregiving experiences, health literacy, psychological status, caregiving burden, and family social support. CONCLUSION: There were differences in how informal caregivers perceived the risks associated with caring for functionally dependent elderly individuals at home, which various factors could influence. It was essential to provide training that covered the knowledge and skills needed for caregiving, improve caregivers' awareness of safety risks, and establish a correct perception of caregiving risks. The government must construct and refine a comprehensive framework for caregiver respite services. Simultaneously, healthcare professionals should proactively undertake health education endeavors to augment the recognition of care safety risks among informal caregivers, thereby cultivating an accurate awareness of care risk perception.

18.
BMC Oral Health ; 24(1): 891, 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39098909

RESUMO

BACKGROUND: Periodontitis is associated with poor pregnancy outcomes, indicating periodontal health as an important health concern for pregnant women. Herein, this study identified risk indicators for periodontitis and developed a nomogram for predicting the risk of periodontitis in pregnancy by analyzing periodontitis and associated factors in pregnant women. MATERIALS AND METHODS: A community-based cross-sectional study was conducted by including 438 pregnant women at 10-36 gestational weeks from Langfang, China. Pregnant women were examined for periodontal status, and their demographic, socioeconomic, and oral health behavior data were collected. Potential influencing factors of periodontitis were analyzed with univariate and multivariate logistic regression analyses. A nomogram was developed, followed by the assessment of its validation and discriminatory abilities. RESULTS: The prevalence of periodontitis was 59.8% in pregnant women. Periodontitis-associated variables in pregnant women were gestational age, non-first pregnancy, daily tooth brushing frequency of ≤ 1 before pregnancy, and annual frequency of periodontal treatment < 1 (including no periodontal treatment). The risk of periodontitis was positively associated with gestational age (OR = 1.28, 95% CI = 1.17-1.39, p < 0.001). Pregnancy history showed a strong positive association (OR = 6.57, 95% CI = 1.22-35.43, p = 0.03). Daily tooth brushing frequency before pregnancy was also positively associated with periodontitis (OR = 1.54, 95% CI = 1.03-2.79, p = 0.05). Additionally, the annual frequency of periodontal treatment exhibited a positive association, with higher odds observed for those with less frequent treatment (OR = 2.28, 95% CI = 1.25-4.14, p = 0.05; OR = 7.37, 95% CI = 3.04-22.06, p < 0.001). These four factors were used to develop a nomogram for predicting periodontitis in pregnant women. The area under the receiver operating characteristic curve of the nomogram was 0.855 and 0.831 in the training and testing cohorts, respectively, reflecting the superior prediction accuracy of the nomogram. The calibration curve and decision curve analysis demonstrated the good performance and net benefit of the nomogram. CONCLUSION: Risk factors for periodontitis in pregnant Chinese women include gestational age, non-first pregnancy, lower frequency of daily tooth brushing before pregnancy, and lower frequency of periodontal treatment. An easy-to-use nomogram with acceptable accuracy can allow for the prediction of periodontitis risk in pregnant Chinese women. CLINICAL RELEVANCE: With the assistance of this nomogram, clinicians can evaluate the risk of periodontitis in pregnancy, thereby offering more tailored oral health education to women of reproductive age.


Assuntos
Comportamentos Relacionados com a Saúde , Nomogramas , Periodontite , Complicações na Gravidez , Humanos , Feminino , Gravidez , China/epidemiologia , Adulto , Estudos Transversais , Periodontite/epidemiologia , Complicações na Gravidez/epidemiologia , Fatores de Risco , Saúde Bucal/estatística & dados numéricos , Fatores Socioeconômicos , Prevalência , Fatores Sociodemográficos , População do Leste Asiático
19.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2222-2229, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38812237

RESUMO

This study aims to investigate the effect and mechanism of Stellera chamaejasme extract(SCL) on multidrug resistance(MDR) in breast cancer. Human triple-negative breast cancer cell line MDA-MB-231 and its adriamycin-resistant cell line MDA-MB-231/ADR were used in the experiment. Cell viability was detected by methyl thiazolyl tetrazolium(MTT) assay, and cell apoptosis was detected by DAPI staining and Annexin-V/Pi double staining. Western blot(WB) was used to detect the expression levels of Keap1, Nrf2, HO-1, Bcl-2, Bax, caspase-9, and caspase-3. Immunofluorescence staining was used to observe the distribution of Nrf2 in the cell, and flow cytometry was used to detect the level of reactive oxygen species(ROS) in the cell. The results showed that the resis-tance factor of SCL was 0.69, and that of adriamycin and paclitaxel was 8.40 and 16.36, respectively. DAPI staining showed that SCL could cause nuclear shrinkage and fragmentation of breast cancer cells. Annexin-V/Pi double staining showed that the average apoptosis rate of the drug-resistant cells was 32.64% and 50.29%, respectively under medium and high doses of SCL. WB results showed that SCL could significantly reduce the expression levels of anti-apoptotic proteins Bcl-2, caspase-9, and caspase-3 and significantly increase the expression level of pro-apoptotic protein Bax. Further studies showed that SCL could significantly promote the expression of Keap1, significantly inhibit the expression of Nrf2 and HO-1, and significantly reduce the expression level of Nrf2 in the nucleus. Correspondingly, flow cytometry showed that the intracellular ROS level was significantly increased. In conclusion, SCL can significantly inhibit the proliferation of MDA-MB-231 multidrug-resistant cells of triple-negative breast cancer and cause cell apoptosis, and the mechanism is related to inhibiting Keap1/Nrf2 signaling pathway, leading to ROS accumulation in drug-resistant cells and increasing the expression of apoptosis-related proteins.


Assuntos
Apoptose , Resistencia a Medicamentos Antineoplásicos , Fator 2 Relacionado a NF-E2 , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Feminino , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Thymelaeaceae/química , Medicamentos de Ervas Chinesas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Doxorrubicina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proliferação de Células/efeitos dos fármacos , Células MDA-MB-231
20.
Glia ; 71(3): 602-615, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36353976

RESUMO

In response to central nervous system (CNS) injury, astrocytes go through a series of alterations, referred to as reactive astrogliosis, ranging from changes in gene expression and cell hypertrophy to permanent astrocyte borders around stromal cell scars in CNS lesions. The mechanisms underlying injury-induced reactive astrocytes in the adult CNS have been extensively studied. However, little is known about injury-induced reactive astrocytes during early postnatal development. Astrocytes in the mouse cortex are mainly produced through local proliferation during the first 2 weeks after birth. Here we show that Sox2, a transcription factor critical for stem cells and brain development, is expressed in the early postnatal astrocytes and its expression level was increased in reactive astrocytes after traumatic brain injury (TBI) at postnatal day (P) 7 in the cortex. Using a tamoxifen-induced hGFAP-CreERT2; Sox2flox/flox ; Rosa-tdT mouse model, we found that specific knockout of Sox2 in astrocytes greatly inhibited the proliferation of reactive astrocytes, the formation of glia limitans borders and subsequently promoted the tissue recovery after postnatal TBI at P7 in the cortex. In addition, we found that injury-induced glia limitans borders were still formed at P2 in the wild-type mouse cortex, and knockout of Sox2 in astrocytes inhibited the reactivity of both astrocytes and microglia. Together, these findings provide evidence that Sox2 is essential for the reactivity of astrocytes in response to the cortical TBI during the early postnatal period and suggest that Sox2-dependent astrocyte reactivity is a potential target for therapeutic treatment after TBI.


Assuntos
Astrócitos , Lesões Encefálicas Traumáticas , Fatores de Transcrição SOXB1 , Animais , Camundongos , Astrócitos/metabolismo , Lesões Encefálicas Traumáticas/patologia , Sistema Nervoso Central/metabolismo , Gliose/patologia , Neuroglia/metabolismo , Fatores de Transcrição SOXB1/genética , Camundongos Knockout
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