Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 317
Filtrar
1.
Plant J ; 119(1): 252-265, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38596892

RESUMO

Chicoric acid is the major active ingredient of the world-popular medicinal plant purple coneflower (Echinacea purpurea (L.) Menoch). It is recognized as the quality index of commercial hot-selling Echinacea products. While the biosynthetic pathway of chicoric acid in purple coneflower has been elucidated recently, its regulatory network remains elusive. Through co-expression and phylogenetic analysis, we found EpMYB2, a typical R2R3-type MYB transcription factor (TF) responsive to methyl jasmonate (MeJA) simulation, is a positive regulator of chicoric acid biosynthesis. In addition to directly regulating chicoric acid biosynthetic genes, EpMYB2 positively regulates genes of the upstream shikimate pathway. We also found that EpMYC2 could activate the expression of EpMYB2 by binding to its G-box site, and the EpMYC2-EpMYB2 module is involved in the MeJA-induced chicoric acid biosynthesis. Overall, we identified an MYB TF that positively regulates the biosynthesis of chicoric acid by activating both primary and specialized metabolic genes. EpMYB2 links the gap between the JA signaling pathway and chicoric acid biosynthesis. This work opens a new direction toward engineering purple coneflower with higher medicinal qualities.


Assuntos
Ácidos Cafeicos , Echinacea , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Succinatos , Fatores de Transcrição , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Succinatos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ácidos Cafeicos/metabolismo , Echinacea/genética , Echinacea/metabolismo , Oxilipinas/metabolismo , Oxilipinas/farmacologia , Ciclopentanos/metabolismo , Ciclopentanos/farmacologia , Filogenia , Acetatos/farmacologia
2.
Immunology ; 172(4): 566-576, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38618995

RESUMO

The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular , Caspase 8 , Enzima Desubiquitinante CYLD , Lipopolissacarídeos , Proteína Serina-Treonina Quinases de Interação com Receptores , Transdução de Sinais , Receptor 4 Toll-Like , Caspase 8/metabolismo , Caspase 8/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Enzima Desubiquitinante CYLD/metabolismo , Enzima Desubiquitinante CYLD/genética , Animais , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Camundongos , Humanos , Regulação da Expressão Gênica , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Knockout , Camundongos Endogâmicos C57BL , Proteína de Domínio de Morte Associada a Fas
3.
Drug Metab Dispos ; 52(6): 555-564, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38565301

RESUMO

Cytochrome P450 1A2 (CYP1A2) is a known tumor suppressor in hepatocellular carcinoma (HCC), but its expression is repressed in HCC and the underlying mechanism is unclear. In this study, we investigated the epigenetic mechanisms of CYP1A2 repression and potential therapeutic implications. In HCC tumor tissues, the methylation rates of CYP1A2 CpG island (CGI) and DNA methyltransferase (DNMT) 3A protein levels were significantly higher, and there was a clear negative correlation between DNMT3A and CYP1A2 protein expression. Knockdown of DNMT3A by siRNA significantly increased CYP1A2 expression in HCC cells. Additionally, treating HCC cells with decitabine (DAC) resulted in a dose-dependent upregulation of CYP1A2 expression by reducing the methylation level of CYP1A2 CGI. Furthermore, we observed a decreased enrichment of H3K27Ac in the promoter region of CYP1A2 in HCC tissues. Treatment with the trichostatin A (TSA) restored CYP1A2 expression in HCC cells by increasing H3K27Ac levels in the CYP1A2 promoter region. Importantly, combination treatment of sorafenib with DAC or TSA resulted in a leftward shift of the dose-response curve, lower IC50 values, and reduced colony numbers in HCC cells. Our findings suggest that hypermethylation of the CGI at the promoter, mediated by the high expression of DNMT3A, and hypoacetylation of H3K27 in the CYP1A2 promoter region, leads to CYP1A2 repression in HCC. Epigenetic drugs DAC and TSA increase HCC cell sensitivity to sorafenib by restoring CYP1A2 expression. Our study provides new insights into the epigenetic regulation of CYP1A2 in HCC and highlights the potential of epigenetic drugs as a therapeutic approach for HCC. SIGNIFICANCE STATEMENT: This study marks the first exploration of the epigenetic mechanisms underlying cytochrome P450 (CYP) 1A2 suppression in hepatocellular carcinoma (HCC). Our findings reveal that heightened DNA methyltransferase expression induces hypermethylation of the CpG island at the promoter, coupled with diminished H3K27Ac levels, resulting in the repression of CYP1A2 in HCC. The use of epigenetic drugs such as decitabine and trichostatin A emerges as a novel therapeutic avenue, demonstrating their potential to restore CYP1A2 expression and enhance sorafenib sensitivity in HCC cells.


Assuntos
Carcinoma Hepatocelular , Citocromo P-450 CYP1A2 , Metilação de DNA , Epigênese Genética , Neoplasias Hepáticas , Sorafenibe , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Humanos , Sorafenibe/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/genética , Metilação de DNA/efeitos dos fármacos , Linhagem Celular Tumoral , Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP1A2/metabolismo , DNA Metiltransferase 3A , Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Decitabina/farmacologia , Ilhas de CpG/genética , Ácidos Hidroxâmicos/farmacologia , Regiões Promotoras Genéticas/genética , Regiões Promotoras Genéticas/efeitos dos fármacos
4.
Brain Behav Immun ; 119: 171-187, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38565398

RESUMO

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.


Assuntos
Barreira Hematoencefálica , Disfunção Cognitiva , Disbiose , Emulsificantes , Microbioma Gastrointestinal , Polissorbatos , Animais , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Polissorbatos/farmacologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/induzido quimicamente , Emulsificantes/metabolismo , Emulsificantes/farmacologia , Disbiose/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Envelhecimento/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Masculino , Microglia/metabolismo , Microglia/efeitos dos fármacos , Eixo Encéfalo-Intestino/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ácidos e Sais Biliares/metabolismo
5.
Inorg Chem ; 63(1): 795-802, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38109223

RESUMO

The conversion of diluted CO2 into tunable syngas via photocatalysis is critical for implementing CO2 reduction practically, although the efficiency remains low. Herein, we report the use of graphene-modified transition metal hydroxides, namely, NiXCo1-X-GR, for the conversion of diluted CO2 into syngas with adjustable CO/H2 ratios, utilizing Ru dyes as photosensitizers. The Ni(OH)2-GR cocatalyst can generate 12526 µmol g-1 h-1 of CO and 844 µmol g-1 h-1 of H2, while the Co(OH)2-GR sample presents a generation rate of 2953 µmol g-1 h-1 for CO and 10027 µmol g-1 h-1 for H2. Notably, by simply altering the addition amounts of nickel and cobalt in the transition metal composite, the CO/H2 ratios in syngas can be easily regulated from 18:1 to 1:4. Experimental characterization of composites and DFT calculations suggest that the differing adsorption affinities of CO2 and H2O over Ni(OH)2-GR and Co(OH)2-GR play a significant role in determining the selectivity of CO and H2 products, ultimately affecting the CO/H2 ratios in syngas. Overall, these findings demonstrate the potential of graphene-modified transition metal hydroxides as efficient photocatalysts for CO2 reduction and syngas production.

6.
J Immunol ; 208(10): 2309-2318, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428692

RESUMO

Classical activation of macrophage and monocyte differentiation induced by ß-glucan is accompanied with metabolic change in glucose. However, the role of the metabolic rewiring in monocyte/macrophage activation remains elusive. In this study, we show that berberine induces aerobic glycolysis by blocking the tricarboxylic acid cycle and modulates cytokine responses in bone marrow-derived macrophages (BMDMs) from mice and human PBMC. 13-Methyberberine had activities on glucose metabolism and BMDM activation similar to those of berberine, whereas other tested derivatives lost both activities. Glucose transporter (GLUT)1 expression and total cellular hexokinase activity increased gradually in BMDMs in the presence of berberine. In the contrast, LPS upregulated GLUT1 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) levels in 6 h. Extracellular glucose levels and replacing glucose with galactose in culture medium affected the cytokine secretion of BMDMs. Berberine alleviated enteritis of Salmonella typhimurium infection and protected mice against endotoxic shock. In mice i.p. injected with LPS, the increase of serum TNF-α and the drop of blood glucose were attenuated by berberine treatment. These data together demonstrated that macrophage activation was closely related with glucose metabolism.


Assuntos
Berberina , Ativação de Macrófagos , Animais , Berberina/farmacologia , Glucose , Glicólise , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/metabolismo , Camundongos , Fosfofrutoquinase-2/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
BMC Biol ; 21(1): 235, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880634

RESUMO

BACKGROUND: Severe peripheral nerve injury (PNI) often leads to significant movement disorders and intractable pain. Therefore, promoting nerve regeneration while avoiding neuropathic pain is crucial for the clinical treatment of PNI patients. However, established animal models for peripheral neuropathy fail to accurately recapitulate the clinical features of PNI. Additionally, researchers usually investigate neuropathic pain and axonal regeneration separately, leaving the intrinsic relationship between the development of neuropathic pain and nerve regeneration after PNI unclear. To explore the underlying connections between pain and regeneration after PNI and provide potential molecular targets, we performed single-cell RNA sequencing and functional verification in an established rat model, allowing simultaneous study of the neuropathic pain and axonal regeneration after PNI. RESULTS: First, a novel rat model named spared nerve crush (SNC) was created. In this model, two branches of the sciatic nerve were crushed, but the epineurium remained unsevered. This model successfully recapitulated both neuropathic pain and axonal regeneration after PNI, allowing for the study of the intrinsic link between these two crucial biological processes. Dorsal root ganglions (DRGs) from SNC and naïve rats at various time points after SNC were collected for single-cell RNA sequencing (scRNA-seq). After matching all scRNA-seq data to the 7 known DRG types, we discovered that the PEP1 and PEP3 DRG neuron subtypes increased in crushed and uncrushed DRG separately after SNC. Using experimental design scRNA-seq processing (EDSSP), we identified Adcyap1 as a potential gene contributing to both pain and nerve regeneration. Indeed, repeated intrathecal administration of PACAP38 mitigated pain and facilitated axonal regeneration, while Adcyap1 siRNA or PACAP6-38, an antagonist of PAC1R (a receptor of PACAP38) led to both mechanical hyperalgesia and delayed DRG axon regeneration in SNC rats. Moreover, these effects can be reversed by repeated intrathecal administration of PACAP38 in the acute phase but not the late phase after PNI, resulting in alleviated pain and promoted axonal regeneration. CONCLUSIONS: Our study reveals that Adcyap1 is an intrinsic protective factor linking neuropathic pain and axonal regeneration following PNI. This finding provides new potential targets and strategies for early therapeutic intervention of PNI.


Assuntos
Axônios , Neuralgia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Animais , Ratos , Axônios/fisiologia , Gânglios Espinais/fisiologia , Regeneração Nervosa/genética , Neuralgia/genética , Neurônios , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Fatores de Proteção , Ratos Sprague-Dawley , Análise de Sequência de RNA
8.
Perfusion ; : 2676591231226159, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38171385

RESUMO

BACKGROUND: Hyperlactatemia (HL) during cardiopulmonary bypass (CPB) is relatively frequent in infants and associates with increased morbidity and mortality. Studies on adults have shown that carbon dioxide production index (VCO2i) during CPB is linked to the occurrence of HL, with 'critical thresholds' for VCO2i reported to be 60 mL/min/m2. However, considering infants have a higher metabolic rate and lower tolerance to hypoxia, the critical threshold of VCO2i in infants cannot be replied to the existing adults' standards. The objective of this study is to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in infants. METHODS: VCO2i predicts hyperlactatemia during cardiopulmonary bypass in pediatric cardiac surgery (pGDP-VCO2i) is a nested case-control study. A cohort of consecutive pediatric patients of less than 3 years of age, undergoing congenital cardiac surgeries between May 2021 and December 2023 in West China Hospital will be enrolled. The VCO2i levels of each patient will be recorded every 5 min during CPB. The primary outcome is the rate of HL. The infants will be divided into two groups based on the presence or not of HL. Pre- and intraoperative factors will be tested for independent association with HL. Then, we will make an analysis, and the critical value of VCO2i will be obtained. The postoperative outcome of patients with or without HL will be compared. DISCUSSION: This will be the first trial to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in pediatrics. The results of this study are expected to lay a foundation for clinical application of goal-directed perfusion (GDP) management strategy, and optimize the perfusion strategy and improve the prognosis of pediatric patients undergoing cardiac surgery. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR2100044296 on 16 March 2021.

9.
Sensors (Basel) ; 24(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38894191

RESUMO

This article discusses the use of distributed acoustic sensing (DAS) for monitoring gas-liquid two-phase slug flow in horizontal pipes, using standard telecommunication fiber optics connected to a DAS integrator for data acquisition. The experiments were performed in a 14 m long, 5 cm diameter transparent PVC pipe with a fiber cable helically wrapped around the pipe. Using mineral oil and compressed air, the system captured various flow rates and gas-oil ratios. New algorithms were developed to characterize slug flow using DAS data, including slug frequency, translational velocity, and the lengths of slug body, slug unit, and the liquid film region that had never been discussed previously. This study employed a high-speed camera next to the fiber cable sensing section for validation purposes and achieved a good correlation among the measurements under all conditions tested. Compared to traditional multiphase flow sensors, this technology is non-intrusive and offers continuous, real-time measurement across long distances and in harsh environments, such as subsurface or downhole conditions. It is cost-effective, particularly where multiple measurement points are required. Characterizing slug flow in real time is crucial to many industries that suffer slug-flow-related issues. This research demonstrated the DAS's potential to characterize slug flow quantitively. It will offer the industry a more optimal solution for facility design and operation and ensure safer operational practices.

10.
Molecules ; 29(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38398666

RESUMO

Although nano SiO2 exhibits excellent application potential in the field of oil and gas exploration and development, such as drilling fluid, enhanced oil/gas recovery, etc., it is prone to agglomeration and loses its effectiveness due to the action of cations in saline environments of oil and gas reservoirs. Therefore, it is crucial to study the mechanism of the change in energy between nano SiO2 and cations for its industrial application. In this paper, the effect of cations (Na+, K+, Ca2+, and Mg2+) on the surface energy of nano SiO2 particles is investigated from the perspective of molecular motion and electronic change by density functional theory. The results are as follows: Due to the electrostatic interactions, cations can migrate towards the surface of nano SiO2 particles. During the migration process, monovalent cations are almost unaffected by water molecules, and they can be directly adsorbed on the surface by nano SiO2 particles. However, when divalent cations migrate from a distance to the surface of nano SiO2 particles, they can combine with water molecules to create an energy barrier, which can prevent them from moving forward. When divalent cations break through the energy barrier, the electronic kinetic energy between them and nano SiO2 particles changes more strongly, and the electrons carried by them are more likely to break through the edge of the atomic nucleus and undergo charge exchange with nano SiO2 particles. The change in interaction energy is more intense, which can further disrupt the configuration stability of nano SiO2. The interaction energy between cations and nano SiO2 particles mainly comes from electrostatic energy, followed by Van der Waals energy. From the degree of influence of four cations on nano SiO2 particles, the order from small to large is as follows: K+ < Na+ < Mg2+ < Ca2+. The research results can provide a theoretical understanding of the interaction between nano SiO2 particles and cations during the application of nano SiO2 in the field of oil and gas exploration and development.

11.
Bull Environ Contam Toxicol ; 112(4): 51, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38556558

RESUMO

Esketamine (ESK) is the S-enantiomer of ketamine racemate (a new psychoactive substance) that can result in illusions, and alter hearing, vision, and proprioception in human and mouse. Up to now, the neurotoxicity caused by ESK at environmental level in fish is still unclear. This work studied the effects of ESK on behaviors and transcriptions of genes in dopamine and GABA pathways in zebrafish larvae at ranging from 12.4 ng L- 1 to 11141.1 ng L- 1 for 7 days post fertilization (dpf). The results showed that ESK at 12.4 ng L- 1 significantly reduced the touch response of the larvae at 48 hpf. ESK at 12.4 ng L- 1 also reduced the time and distance of larvae swimming at the outer zone during light period, which implied that ESK might potentially decrease the anxiety level of larvae. In addition, ESK increased the transcription of th, ddc, drd1a, drd3 and drd4a in dopamine pathway. Similarly, ESK raised the transcription of slc6a1b, slc6a13 and slc12a2 in GABA pathway. This study suggested that ESK could affect the heart rate and behaviors accompanying with transcriptional alterations of genes in DA and GABA pathways at early-staged zebrafish, which resulted in neurotoxicity in zebrafish larvae.


Assuntos
Dopamina , Ketamina , Humanos , Animais , Camundongos , Dopamina/metabolismo , Dopamina/farmacologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Ketamina/metabolismo , Ketamina/farmacologia , Larva , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia
12.
Entropy (Basel) ; 26(7)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39056952

RESUMO

While collecting training data, even with the manual verification of experts from crowdsourcing platforms, eliminating incorrect annotations (noisy labels) completely is difficult and expensive. In dealing with datasets that contain noisy labels, over-parameterized deep neural networks (DNNs) tend to overfit, leading to poor generalization and classification performance. As a result, noisy label learning (NLL) has received significant attention in recent years. Existing research shows that although DNNs eventually fit all training data, they first prioritize fitting clean samples, then gradually overfit to noisy samples. Mainstream methods utilize this characteristic to divide training data but face two issues: class imbalance in the segmented data subsets and the optimization conflict between unsupervised contrastive representation learning and supervised learning. To address these issues, we propose a Balanced Partitioning and Training framework with Pseudo-Label Relaxed contrastive loss called BPT-PLR, which includes two crucial processes: a balanced partitioning process with a two-dimensional Gaussian mixture model (BP-GMM) and a semi-supervised oversampling training process with a pseudo-label relaxed contrastive loss (SSO-PLR). The former utilizes both semantic feature information and model prediction results to identify noisy labels, introducing a balancing strategy to maintain class balance in the divided subsets as much as possible. The latter adopts the latest pseudo-label relaxed contrastive loss to replace unsupervised contrastive loss, reducing optimization conflicts between semi-supervised and unsupervised contrastive losses to improve performance. We validate the effectiveness of BPT-PLR on four benchmark datasets in the NLL field: CIFAR-10/100, Animal-10N, and Clothing1M. Extensive experiments comparing with state-of-the-art methods demonstrate that BPT-PLR can achieve optimal or near-optimal performance.

13.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1082-1090, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38621915

RESUMO

This study aims to investigate the impact of Kuntai Capsules(KTC) on polycystic ovarian syndrome(PCOS) rat models and explore the underlying mechanism. Fifty female SD rats were randomly divided into five groups(10 rats in each group), including control group, model group, low-, medium-, and high-dose KTC group. Except for the control group, the other groups were injected with dehydroepiandrosterone(DHEA) combined with a high-fat diet(HFD) to induce the PCOS rat model for 28 days. 0.315, 0.63, and 1.26 g·kg~(-1)·d~(-1) KTC was dissolved in the same amount of normal saline and given to low-, medium-, and high-dose KTC groups by gavage. Both control group and model group were given the same amount of normal saline for 15 days. After administration, fasting blood glucose(FBG) was measured by a glucose meter. Fasting insulin(FINS), luteinizing hormone(LH), testosterone(T), and follicle-stimulating hormone(FSH) were detected by enzyme-linked immunosorbent assay(ELISA), and LH/FSH ratio and insulin resistance index(HOMA-IR) were calculated. The pathological morphology of ovarian tissue was observed by hematoxylin-eosin(HE) staining. The expression levels of collagen α type Ⅲ 1 chain(COL3A1), apoptotic factors Bax, and Bcl-2 were detected using Western blot and immunofluorescence. The mRNA expressions of COL3A1, Bax, and Bcl-2 in ovarian tissue were performed by real-time PCR(RT-PCR). The results show that compared with the control group, the body weight, serum levels of FBG, FINS, LH, T, LH/FSH, and HOMA-IR are higher in model group(P<0.05 or P<0.01), and the level of FSH is lower(P<0.05). In model group, a large number of white blood cells are found in the vaginal exfoliated cells, mainly in the interictal phase. There are more cystic prominences on the surface of the ovary. The thickness of the granular cell layer is reduced, and oocytes are absent. COL3A1 and Bax protein expression levels are increased(P<0.01), while Bcl-2 protein expression levels are decreased(P<0.05) in the ovarian tissue COL3A1 and Bax mRNA expression levels are increased in ovarian tissue(P<0.05). Compared with the model group, the body weight, FBG, FINS, LH, T, LH/FSH, and HOMA-IR in low-, medium-, and high-dose KTC groups are decreased(P<0.05 or P<0.01), while the levels of FSH in medium-, and high-dose KTC groups are increased(P<0.05 or P<0.01). Low-, medium-, and high-dose KTC groups gradually show a stable interictal phase. The surface of the ovary is smooth. Oocytes and mature follicles can be seen in ovarian tissue, and the thickness of the granular cell layer is increased. The expression level of COL3A1 protein decreases in low-and medium-dose KTC groups(P<0.05 or P<0.01), and that of Bax protein decreases in low-dose KTC group(P<0.05 or P<0.01), and the expression level of Bcl-2 protein increases in low-dose KTC group(P<0.01). The expression levels of COL3A1 and Bax mRNA decreased in the low-dose KTC group(P<0.05), while the expression levels of Bcl-2 mRNA increased(P<0.05). In summary, KTC can inhibit ovarian granulosa cell apoptosis and reduce follicular atresia by regulating the AGE-RAGE signaling pathway. It can promote insulin secretion, reduce blood sugar and body weight, restore serum hormone levels, improve symptoms of PCOS, alleviate morphological damage of the ovary, and restore ovarian function, which is of great value in the treatment of PCOS.


Assuntos
Síndrome do Ovário Policístico , Humanos , Ratos , Feminino , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/genética , Proteína X Associada a bcl-2 , Solução Salina , Ratos Sprague-Dawley , Atresia Folicular , Transdução de Sinais , Peso Corporal , Hormônio Foliculoestimulante , RNA Mensageiro
14.
Plant J ; 110(3): 802-813, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35141962

RESUMO

High pliability and promiscuity are observed widely exist in plant specialized metabolism, especially the hydroxycinnamic acid metabolism. Here, we identified an addition BAHD acyltransferase (EpHMT) that catalyzes phaselic acid biosynthesis and found that the substrate promiscuities of identified BAHD and SCPL acyltransferases are responsible for the diversity of hydroxycinnamic acid derivatives in purple coneflower.


Assuntos
Produtos Biológicos , Echinacea , Aciltransferases/genética , Aciltransferases/metabolismo , Ácidos Cumáricos , Echinacea/metabolismo , Plantas/metabolismo
15.
Infect Immun ; 91(5): e0010023, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37052497

RESUMO

Streptococcus pneumoniae relies on two-component systems (TCSs) to regulate the processes of pathogenicity, osmotic pressure, chemotaxis, and energy metabolism. The TCS01 system of S. pneumoniae is composed of HK01 (histidine kinase) and RR01 (response regulator). Previous studies have reported that an rr01 mutant reduced the pneumococcal virulence in rat pneumonia, bacteremia, a nasopharyngeal model, and infective endocarditis. However, the mechanism of TCS01 (HK/RR01) regulating pneumococcal virulence remains unclear. Here, pneumococcal mutant strains Δrr01, Δhk01, and Δrr01&hk01 were constructed, and bacterial adhesion and invasion to A549 cells were compared. RNA sequencing was performed in D39 wild-type and Δrr01 strains, and transcript profile changes were analyzed. Differentially expressed virulence genes in the Δrr01 strain were screened out and identified by quantitative real-time PCR (qRT-PCR). Our results showed that pneumococcal mutant strains exhibited attenuated adhesion and invasion to A549 cells and differential transcript profiles. Results of qRT-PCR identification showed that the differential virulence genes screened out were downregulated. Among those changed virulence genes in the Δrr01 strain, the downregulated expression level of choline binding protein pcpA was the most obvious. Complementation of rr01 and overexpression of pcpA in the Δrr01 strain partially restored both pneumococcal adhesion and invasion, and rr01 complementation made the expression of pcpA upregulated. These findings revealed that rr01 influenced pneumococcal virulence by regulating pcpA.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Infecções Pneumocócicas , Streptococcus pneumoniae , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células A549 , Humanos , Infecções Pneumocócicas/metabolismo , Infecções Pneumocócicas/microbiologia , Aderência Bacteriana
16.
Planta ; 257(6): 110, 2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37149499

RESUMO

MAIN CONCLUSION: Based on phenotypic, physiological and proteomic analysis, the possible mechanism by which Ds-26-16 regulates salt tolerance in Arabidopsis seedlings was revealed. Functional and mechanistic characterization of salt tolerance genes isolated from natural resources is crucial for their application. In this study, we report the possible mechanism by which Ds-26-16, a gene from Dunaliella, and its point mutation gene EP-5, enhance salt tolerance in Arabidopsis seedlings. Both Ds-26-16 and EP-5 transgenic lines displayed higher seed germination rates, cotyledon-greening rates, soluble sugar contents, decreased relative conductivity and ROS accumulation when germinating under 150 mM NaCl conditions. Comparative proteomic analysis revealed that there were 470 or 391 differentially expressed proteins (DEPs) in Ds-26-16 or EP-5, respectively, compared with the control (3301) under salt stress. The GO and KEGG enrichment analyses showed the DEPs in Ds-26-16 vs. 3301 and EP-5 vs. 3301 were similar and mainly enriched in photosynthesis, regulation of gene expression, carbohydrate metabolism, redox homeostasis, hormonal signal and defense, and regulation of seed germination. Thirty-seven proteins were found to be stably expressed under salt stress due to the expression of Ds-26-16, and eleven of them contain the CCACGT motif which could be bound by the transcription factor in ABA signaling to repress gene transcription. Taken together, we propose that Ds-26-16, as a global regulator, improves salt-tolerance by coordinating stress-induced signal transduction and modulating multiple responses in Arabidopsis seedlings. These results provide valuable information for utilizing natural resources in crop improvement for breeding salt-tolerant crops.


Assuntos
Arabidopsis , Clorofíceas , Plântula/genética , Arabidopsis/metabolismo , Tolerância ao Sal/genética , Proteômica , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/genética , Germinação/genética
17.
Plant Cell ; 32(4): 984-999, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32051210

RESUMO

Starch is the major storage carbohydrate in plants and functions in buffering carbon and energy availability for plant fitness with challenging environmental conditions. The timing and extent of starch degradation appear to be determined by diverse hormonal and environmental signals; however, our understanding of the regulation of starch metabolism is fragmentary. Here, we demonstrate that the phytohormone brassinosteroid (BR) and redox signal hydrogen peroxide (H2O2) induce the breakdown of starch in guard cells, which promotes stomatal opening. The BR-insensitive mutant bri1-116 accumulated high levels of starch in guard cells, impairing stomatal opening in response to light. The gain-of-function mutant bzr1-1D suppressed the starch excess phenotype of bri1-116, thereby promoting stomatal opening. BRASSINAZOLE-RESISTANT1 (BZR1) interacts with the basic leucine zipper transcription factor G-BOX BINDING FACTOR2 (GBF2) to promote the expression of ß-AMYLASE1 (BAM1), which is responsible for starch degradation in guard cells. H2O2 induces BZR1 oxidation, enhancing the interaction between BZR1 and GBF2 to increase BAM1 transcription. Mutations in BAM1 lead to starch accumulation and reduce the effects of BR and H2O2 on stomatal opening. Overall, this study uncovers the critical roles of BR and H2O2 in regulating guard cell starch metabolism and stomatal opening.


Assuntos
Brassinosteroides/farmacologia , Peróxido de Hidrogênio/farmacologia , Estômatos de Plantas/citologia , Estômatos de Plantas/fisiologia , Amido/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Modelos Biológicos , Mutação/genética , Estômatos de Plantas/efeitos dos fármacos
18.
Environ Sci Technol ; 57(36): 13384-13396, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37651267

RESUMO

Imidacloprid (IMI) and thiamethoxam (THM) are ubiquitous in aquatic ecosystems. Their negative effects on parental fish are investigated while intergenerational effects at environmentally relevant concentrations remain unclear. In this study, F0 zebrafish exposed to IMI and THM (0, 50, and 500 ng L-1) for 144 days post-fertilization (dpf) was allowed to spawn with two modes (internal mating and cross-mating), resulting in four types of F1 generations to investigate the intergenerational effects. IMI and THM affected F0 zebrafish fecundity, gonadal development, sex hormone and VTG levels, with accumulations found in F0 muscles and ovaries. In F1 generation, paternal or maternal exposure to IMI and THM also influenced sex hormones levels and elevated the heart rate and spontaneous movement rate. LncRNA-mRNA network analysis revealed that cell cycle and oocyte meiosis-related pathways in IMI groups and steroid biosynthesis related pathways in THM groups were significantly enriched in F1 offspring. Similar transcriptional alterations of dmrt1, insl3, cdc20, ccnb1, dnd1, ddx4, cox4i1l, and cox5b2 were observed in gonads of F0 and F1 generations. The findings indicated that prolonged paternal or maternal exposure to IMI and THM could severely cause intergenerational toxicity, resulting in developmental toxicity and endocrine-disrupting effects in zebrafish offspring.


Assuntos
Exposição Materna , Peixe-Zebra , Animais , Feminino , Humanos , Tiametoxam , Ecossistema
19.
J Opt Soc Am A Opt Image Sci Vis ; 40(6): 1191-1200, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37706772

RESUMO

This paper focuses on a dynamic star image acquisition and matching method for space situational awareness, which can quickly search for widely distributed resident space objects. First, the optical circular rotation imaging method performed by a single space camera is proposed to obtain a series of star images. And then, the image matching method based on graph neural networks is proposed for generating a wide observation star image. Experiment results show that compared with baseline matching algorithms, the matching accuracy and matching precision of the proposed algorithm are improved significantly.

20.
Appl Opt ; 62(10): 2595-2603, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132808

RESUMO

Micro-pore optics (MPO) has been employed in space x-ray telescopes for large field-of-view observations. For x-ray focal plane detectors with visible photon sensing capability, the optical blocking filter (OBF) on MPO devices is critical for preventing signal contamination by those photons. In this work, we designed a piece of equipment to measure the light transmission with high accuracy. The transmittance test results of the MPO plates meet the design requirements of less than 5×10-4. Based on the multilayer homogeneous film matrix method, we estimated possible combinations of film thicknesses (with alumina) that show a good agreement with the OBF design.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA