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1.
Mol Med ; 30(1): 58, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720283

ABSTRACT

BACKGROUND: Vascular calcification (VC) is a complication in diabetes mellitus (DM) patients. Osteogenic phenotype switching of vascular smooth muscle cells (VSMCs) plays a critical role in diabetes-related VC. Mitophagy can inhibit phenotype switching in VSMCs. This study aimed to investigate the role of the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin 4 (EX4) in mitophagy-induced phenotype switching. MATERIALS AND METHODS: The status of VC in T2DM mice was monitored using Von Kossa and Alizarin Red S (ARS) staining in mouse aortic tissue. Human aortic smooth muscle cells were cultured in high glucose (HG) and ß-glycerophosphate (ß-GP) conditioned medium. Accumulation of LC3B and p62 was detected in the mitochondrial fraction. The effect of EX4 in vitro and in vivo was investigated by knocking down AMPKα1. RESULTS: In diabetic VC mice, EX4 decreased the percentage of von Kossa/ARS positive area. EX4 inhibited osteogenic differentiation of HG/ß-GP-induced VSMCs. In HG/ß-GP-induced VSMCs, the number of mitophagosomes was increased, whereas the addition of EX4 restored mitochondrial function, increased the number of mitophagosome-lysosome fusions, and reduced p62 in mitochondrial frictions. EX4 increased the phosphorylation of AMPKα (Thr172) and ULK1 (Ser555) in HG/ß-GP-induced VSMCs. After knockdown of AMPKα1, ULK1 could not be activated by EX4. The accumulation of LC3B and p62 could not be reduced after AMPKα1 knockdown. Knockdown of AMPKα1 negated the therapeutic effects of EX4 on VC of diabetic mice. CONCLUSION: EX4 could promote mitophagy by activating the AMPK signaling pathway, attenuate insufficient mitophagy, and thus inhibit the osteogenic phenotype switching of VSMCs.


Subject(s)
AMP-Activated Protein Kinases , Exenatide , Glucagon-Like Peptide-1 Receptor , Mitophagy , Signal Transduction , Vascular Calcification , Animals , Mitophagy/drug effects , Vascular Calcification/etiology , Vascular Calcification/metabolism , Vascular Calcification/drug therapy , Signal Transduction/drug effects , Mice , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Male , AMP-Activated Protein Kinases/metabolism , Humans , Exenatide/pharmacology , Exenatide/therapeutic use , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Disease Models, Animal , Mice, Inbred C57BL
2.
Curr Med Sci ; 44(2): 247-260, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38622425

ABSTRACT

Extracellular vesicles (EVs) are considered to be a new generation of bioinspired nanoscale drug delivery systems due to their low immunogenicity, natural functionality, and excellent biocompatibility. However, limitations such as low uptake efficiency, insufficient production, and inhomogeneous performance undermine their potential. To address these issues, numerous researchers have put forward various methods and applications for enhancing EV uptake in recent decades. In this review, we introduce various methods for the cellular uptake of EVs and summarize recent advances on the methods and mechanisms for enhancing EV uptake. In addition, we provide further understanding regarding enhancing EV uptake and put forward prospects and challenges for the development of EV-based therapy in the future.


Subject(s)
Extracellular Vesicles , Drug Delivery Systems/methods
3.
J Fluoresc ; 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639858

ABSTRACT

Two fluorescent probes, Y1-2 were synthesized from 2-acetonaphthone, 4-acetylbiphenyl, and phenyl hydrazine by Vilsmeier-Haack reaction and Knoevenagel condensation. Their recognition efficacies for N2H4 were tested by UV-visible absorption spectroscopy and fluorescence emission spectroscopy. The recognition mechanism were studies by density-functional theory calculations, and the effect of pH on N2H4 recognition was also studied. The results showed that the probe Y1-2 has high selectivity and a low detection limit for N2H4, and the recognition of N2H4 can be accomplished at physiological pH. The probes have had obvious aggregation-induced luminescence effect, large Stokes shift, high sensitivity, and can be successfully applied to live cell imaging.

4.
Theor Appl Genet ; 137(3): 54, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38381205

ABSTRACT

KEY MESSAGE: Integrated phenomics, ionomics, genomics, transcriptomics, and functional analyses present novel insights into the role of pectin demethylation-mediated cell wall Na+ retention in positively regulating salt tolerance in oilseed rape. Genetic variations in salt stress tolerance identified in rapeseed genotypes highlight the complicated regulatory mechanisms. Westar is ubiquitously used as a transgenic receptor cultivar, while ZS11 is widely grown as a high-production and good-quality cultivar. In this study, Westar was found to outperform ZS11 under salt stress. Through cell component isolation, non-invasive micro-test, X-ray energy spectrum analysis, and ionomic profile characterization, pectin demethylation-mediated cell wall Na+ retention was proposed to be a major regulator responsible for differential salt tolerance between Westar and ZS11. Integrated analyses of genome-wide DNA variations, differential expression profiling, and gene co-expression networks identified BnaC9.PME47, encoding a pectin methylesterase, as a positive regulator conferring salt tolerance in rapeseed. BnaC9.PME47, located in two reported QTL regions for salt tolerance, was strongly induced by salt stress and localized on the cell wall. Natural variation of the promoter regions conferred higher expression of BnaC9.PME47 in Westar than in several salt-sensitive rapeseed genotypes. Loss of function of AtPME47 resulted in the hypersensitivity of Arabidopsis plants to salt stress. The integrated multiomics analyses revealed novel insights into pectin demethylation-mediated cell wall Na+ retention in regulating differential salt tolerance in allotetraploid rapeseed genotypes. Furthermore, these analyses have provided key information regarding the rapid dissection of quantitative trait genes responsible for nutrient stress tolerance in plant species with complex genomes.


Subject(s)
Arabidopsis , Brassica napus , Brassica rapa , Salt Tolerance/genetics , Brassica napus/genetics , Pectins , Salt Stress , Cell Wall , Demethylation
5.
J Agric Food Chem ; 72(7): 3814-3831, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38329036

ABSTRACT

Common wheat (Triticum aestivum L.) is a global staple food, while nitrogen (N) limitation severely hinders plant growth, seed yield, and grain quality of wheat. Genetic variations in the responses to low N stresses among allohexaploid wheat (AABBDD, 2n = 6x = 42) genotypes emphasize the complicated regulatory mechanisms underlying low N tolerance and N use efficiency (NUE). In this study, hydroponic culture, inductively coupled plasma mass spectrometry, noninvasive microtest, high-performance liquid chromatography, RNA-seq, and bioinformatics were used to determine the differential growth performance, ionome and phytohormone profiles, and genome-wide expression profiling of wheat plants grown under high N and low N conditions. Transcriptional profiling of NPFs, NRT2s, CLCs, SLACs/SLAHs, AAPs, UPSs, NIAs, and GSs characterized the core members, such as TaNPF6.3-6D, TaNRT2.3-3D, TaNIA1-6B, TaGLN1;2-4B, TaAAP14-5A/5D, and TaUPS2-5A, involved in the efficient transport and assimilation of nitrate and organic N nutrients. The low-N-sensitivity wheat cultivar XM26 showed obvious leaf chlorosis and accumulated higher levels of ABA, JA, and SA than the low-N-tolerant ZM578 under N limitation. The TaMYB59-3D-TaNPF7.3/NRT1.5-6D module-mediated shoot-to-root translocation and leaf remobilization of nitrate was proposed as an important pathway regulating the differential responses between ZM578 and XM26 to low N. This study provides some elite candidate genes for the selection and breeding of wheat germplasms with low N tolerance and high NUE.


Subject(s)
Plant Growth Regulators , Triticum , Triticum/genetics , Triticum/metabolism , Plant Growth Regulators/metabolism , Nitrogen/metabolism , Nitrates/metabolism , Plant Breeding
6.
J Agric Food Chem ; 72(4): 2381-2396, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38232380

ABSTRACT

Variations in the resistance to potassium (K) deficiency among rapeseed genotypes emphasize complicated regulatory mechanisms. In this study, a low-K-sensitivity accession (L49) responded to K deficiency with smaller biomasses, severe leaf chlorosis, weaker photosynthesis ability, and deformed stomata morphology compared to a low-K resistant accession (H280). H280 accumulated more K+ than L49 under low K. Whole-genome resequencing (WGS) revealed a total of 5,538,622 single nucleotide polymorphisms (SNPs) and 859,184 insertions/deletions (InDels) between H280 and L49. RNA-seq identified more differentially expressed K+ transporter genes with higher expression in H280 than in L49 under K deficiency. Based on the K+ profiles, differential expression profiling, weighted gene coexpression network analysis, and WGS data between H280 and L49, BnaC4.AKT1 was proposed to be mainly responsible for root K absorption-mediated low K resistance. BnaC4.AKT1 was expressed preferentially in the roots and localized on the plasma membrane. An SNP and an InDel found in the promoter region of BnaC4.AKT1 were proposed to be responsible for its differential expression between rapeseed genotypes. This study identified a gene resource for improving low-K resistance. It also facilitates an integrated knowledge of the differential physiological and transcriptional responses to K deficiency in rapeseed genotypes.


Subject(s)
Brassica napus , Brassica rapa , Potassium Deficiency , Brassica napus/genetics , Brassica napus/metabolism , Potassium Deficiency/genetics , Brassica rapa/metabolism , Genotype , Genomics , Gene Expression Regulation, Plant
7.
Gene ; 894: 148025, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38007163

ABSTRACT

Rapeseed (Brassica napus L.) is susceptible to nutrient stresses during growth and development; however, the CPA (cation proton antiporter) family genes have not been identified in B. napus and their biological functions remain unclear. This study was aimed to identify the molecular characteristics of rapeseed CPAs and their transcriptional responses to multiple nutrient stresses. Through bioinformatics analysis, 117 BnaCPAs, consisting of three subfamilies: Na+/H+ antiporter (NHX), K+ efflux antiporter (KEA), and cation/H+ antiporter (CHX), were identified in the rapeseed genome. Transcriptomic profiling showed that BnaCPAs, particularly BnaNHXs, were transcriptionally responsive to diverse nutrient stresses, including Cd toxicity, K starvation, salt stress, NH4+ toxicity, and low Pi. We found that the salt tolerance of the transgenic rapeseed lines overexpressing BnaA05.NHX2 was significantly higher than that of wild type. Subcellular localization showed that BnaA05.NHX2 was localized on the tonoplast, and TEM combined with X-ray energy spectrum analysis revealed that the vacuolar Na+ concentrations of the BnaA05.NHX2-overexpressing rapeseed plants were significantly higher than those of wild type. The findings of this study will provide insights into the complexity of the BnaCPA family and a valuable resource to explore the in-depth functions of CPAs in B. napus.


Subject(s)
Brassica napus , Brassica rapa , Brassica napus/genetics , Antiporters/genetics , Protons , Brassica rapa/genetics , Vacuoles , Gene Expression Regulation, Plant , Stress, Physiological
8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1019506

ABSTRACT

As color doppler ultrasound listed as the thyroid to regular physical examination project, the positive detection rate of benign and malignant thyroid diseases has increased year by year. The population of patients after thyroid surgery is getting larger and larger, however, the research on how to replace the absent thyroid with exogenous thyroid hormone is not perfect. As the switch of thyroid hormone activation and deactivation, deiodinase plays an important role in maintaining the internal environment of human body. The expression of these enzymes will change with the different needs of each organ in the individual. In the past, many authors have made a detailed description of deiodinase in basic medicine, but the principle of action in clinical aspects is relatively lacking. In this paper, the mechanism of deiodinase was reviewed through literature reading, to explore the basic principle of deiodinase in exogenous thyroid hormone supplementation after thyroid surgery.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1021138

ABSTRACT

Surgical resection is the standard treatment for most patients with thyroid cancer(TC)and is of critical significance for the prognosis of TC.However,clarifying the surgical indications of TC,standardizing the surgical method of TC and formulating rational and personalized treatment strategies are the key to maximizing the curative effect of surgical treatment.In recent years,the global consensus on guidelines related to TC diagnosis and treatment has been rapidly updated,and comprehensive guidelines covering the whole course of the disease and suitable for China's national conditions are urgently needed to keep pace with the times.In this context,the Chinese Anti-Cancer Association(CACA)'s first guidelines for the diagnosis and treatment of thyroid cancer covering all pathologic types,"Chinese Guidelines for the Integrated Diagnosis and Treatment of Cancer-CACA Guidelines for the Diagnosis and Treatment of Thyroid Cancer,"(short as 2022 edition of CACA guidelines)was officially released in April 2022.Based on the authors'personal clinical experience,this paper will interpret the contents of the 2022 edition of CACA guidelines from differentiated TC(DTC)diagnosis,initial treatment and postoperative follow-up from a surgical perspective,explore the particularity and value of surgical treatment strategies in the entire management of TC diagnosis and treatment,and point out areas that deserve to be explored in the future.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1028740

ABSTRACT

AIM To study the phenylethanoid glycosides from Verbenae Herba.METHODS The 80%ethanol extract from Verbenae Herba was isolated and purified by silica gel,Sephadex LH-20,TLC and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Nine compounds were isolated and identified as verbofficoside A(1),cistanoside D(2),epimeredinoside A(3),verbascoside(4),isoverbascoside(5),cistanoside C(6),cistanoside F(7),decaffeoylacteoside(8),jionoside C(9).CONCLUSION Compound 1 is a new compound.Compounds 3 and 6-9 are isolated from this plant for the first time.

11.
Chinese Pharmacological Bulletin ; (12): 201-207, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013588

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

12.
J Fluoresc ; 34(1): 159-167, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37166610

ABSTRACT

A fluorescent probe Y((1,1'-([1,1'-biphenyl]-4,4'-diylbis(3-(2-hydroxyphenyl)-4,5-dihydro-1H-pyrazole-5,1-diyl)) bis(ethan-1-one))) was designed and synthesized, which could be used to Cu2+ and Fe3+ sensors. Through the study of optical properties, the probe Y shows good selectivity and sensitivity to Cu2+ and Fe3+ in aqueous tetrahydrofuran solution [10.0 mM HEPES, pH 7.4, THF-H2O = 9:1(v/v)] with has excellent anti-interference performance, and its detection limits were 0.931 uΜ for Cu2+ and 0.401uΜ for Fe3+. The coordination mechanism of probe Y with Cu2+ and Fe3+ was speculated and verified at DFT level and HRNM. By Hela cytotoxicity and imaging tests, probe Y not only has good biocompatibility, but also can be used for sensing Cu2+ in cells.


Subject(s)
Copper , Fluorescent Dyes , Humans , Fluorescent Dyes/chemistry , Copper/chemistry , Iron/chemistry , HeLa Cells , Optical Imaging , Spectrometry, Fluorescence
13.
Chinese Journal of Radiology ; (12): 266-272, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1027305

ABSTRACT

Objective:To explore brain network properties and their relationship with cognitive function in children with spastic cerebral palsy (SCP) using diffusion tensor imaging (DTI) based graph theory analysis.Methods:The study was a cross-sectional study. Clinical and imaging data of 21 children with SCP (SCP group) and 32 healthy children (control group) who underwent cranial MRI at the Affiliated Hospital of Zunyi Medical University from August 2020 to April 2022 were analyzed retrospectively. 3D-T 1WI, DTI and Wechsler Intelligence Scale were assessed for all subjects. The Wechsler Intelligence Scale included the verbal comprehension index (VCI), the processing speed index (PSI), the work memory index (WMI), and the perceptual reasoning index (PRI), etc., and ultimately the full scale intelligence quotient (FSIQ) scores were obtained based on the indices of each subscale. Independent samples t-test was used to analyze the differences in the small world attributes [small-world index (σ), normalized shortest path length (λ), normalized clustering coefficients (γ)], global attributes [global efficiency (Eglob), local efficiency (Eloc), characteristic path length (Lp), clustering efficiency (Cp)] and node attributes [degree centrality(DC), nodal efficiency (Ne), betweeness centrality (Bc), nodal shortest path length (NLp), nodal clustering efficiency, nodal local efficiency] between two groups of children′s brain networks. Brain network indicators with statistically significant differences between the 2 groups were correlated with Wechsler Intelligence Scale scores using Spearman. Results:The FSIQ scores on the Wechsler Intelligence Scale and the VCI, WMI, PSI, and PRI were lower in the SCP group than in the control group, and the differences were all statistically significant (all P<0.05). Both groups of children′s brain networks had small world properties. Compared with the control group, Eglob decreased, Lp and λ increased in the SCP group (all P<0.05). Compared with the control group, DC and Ne in multiple brain regions decreased, NLp increased in the SCP group (all P<0.05, FDR corrected). Correlation analysis showed that DC in the right parsopercularis was positively correlated with FSIQ, VCI, WMI and PRI( r=0.53, 0.47, 0.47, 0.60, P=0.019, 0.045, 0.044, 0.020, respectively); NLp in the right parsopercularis was negatively correlated with PRI( r=-0.56, P=0.030); Ne in left paracentral, the right parsopercularis, right precentral, right postcentra were positively correlated with PRI( r=0.62, 0.56, 0.53, 0.54, P=0.015, 0.031, 0.044, 0.039, respectively); Ne in the right precentral was positively correlated with WMI ( r=0.48, P=0.039) in the SCP group. Conclusions:There are changes in the topological attributes of global and multiple regional brain networks in SCP. The changes in the attributes of nodes in the right parsopercularis, right precentral, right postcentral, and left paracentral could reflect cognitive dysfunction in children with SCP.

14.
Math Biosci Eng ; 20(10): 17905-17918, 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-38052542

ABSTRACT

Complementary label learning (CLL) is a type of weakly supervised learning method that utilizes the category of samples that do not belong to a certain class to learn their true category. However, current CLL methods mainly rely on rewriting classification losses without fully leveraging the supervisory information in complementary labels. Therefore, enhancing the supervised information in complementary labels is a promising approach to improve the performance of CLL. In this paper, we propose a novel framework called Complementary Label Enhancement based on Knowledge Distillation (KDCL) to address the lack of attention given to complementary labels. KDCL consists of two deep neural networks: a teacher model and a student model. The teacher model focuses on softening complementary labels to enrich the supervision information in them, while the student model learns from the complementary labels that have been softened by the teacher model. Both the teacher and student models are trained on the dataset that contains only complementary labels. To evaluate the effectiveness of KDCL, we conducted experiments on four datasets, namely MNIST, F-MNIST, K-MNIST and CIFAR-10, using two sets of teacher-student models (Lenet-5+MLP and DenseNet-121+ResNet-18) and three CLL algorithms (PC, FWD and SCL-NL). Our experimental results demonstrate that models optimized by KDCL outperform those trained only with complementary labels in terms of accuracy.

15.
Article in English | MEDLINE | ID: mdl-38012369

ABSTRACT

In this paper, four novel hydrazine fluorescent probes X1-X4 with bis-chalcone structure were designed and synthesized. Through the measurement of its optical properties, it is found that it can quickly identify hydrazine, high sensitivity, low detection limit, and good anti-interference ability. The recognition of hydrazine by probes X1-X4 is not affected in the pH range of 4-10, X2 has the highest sensitivity, and the detection limit is as low as 0.336 × 10-7 M. Through Gaussian quantization calculation of probe molecules and their reaction products with hydrazine, it is speculated that the recognition mechanism is the closure of intramolecular charge transfer effect. In addition, the cytotoxicity and imaging of HeLa cells were tested, which showed that probes X1-X4 could be used to detect hydrazine in cells.

16.
J Fluoresc ; 2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37561367

ABSTRACT

Widely utilized in the chemical industry and agriculture, hydrazine is easily absorbed by living things and can cause physical harm when in touch for an extended period of time. As a result, a novel cinnamaldehyde chalcone C5 was produced by Friedel Crafts process and aldol condensation reaction. Triphenylamine was used as the raw material for hydrazine determination in both reactions. Chalcone C5 exhibits significant AIE behavior in a mixed mixture of ethanol and water in addition to having great selectivity and a low detection limit (0.119 nm) for hydrazine. The solvent effect test revealed a linear relationship between the Stokes shift of C5 in the solvent and the rise in solvent orientation polarization. It is important to note that C5 is not harmful to MCF-7 cells, mouse kidney cells, or pig kidney cells. Furthermore, research on cell imaging has demonstrated that probe C5 may be utilized to image the fluorescence of hydrazine in active MCF-7 cells.

17.
Biomed Environ Sci ; 36(6): 501-509, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37424243

ABSTRACT

Objective: This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China. Methods: A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined. Results: BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan). Conclusion: BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.


Subject(s)
Antitubercular Agents , Tuberculosis, Multidrug-Resistant , Adult , Humans , Antitubercular Agents/therapeutic use , Cost-Effectiveness Analysis , Cost-Benefit Analysis , Tuberculosis, Multidrug-Resistant/drug therapy , China/epidemiology
18.
Mater Today Bio ; 21: 100700, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37455821

ABSTRACT

Tissue infection typically results from blood transmission or the direct inoculation of bacteria following trauma. The pathogen-induced destruction of tissue prevents antibiotics from penetrating the infected site, and severe inflammation further impairs the efficacy of conventional treatment. The current study describes the size-dependent induction of macrophage polarization using gold nanoparticles. Gold nanoparticles with a diameter of 50 â€‹nm (Au50) can induce M2 polarization in macrophages by inhibiting the NF-κB signaling pathway and stimulate an inflammatory response in the environment by inhibiting the MAPK signaling pathway LPS. Furthermore, the induced polarization and anti-inflammatory effects of the Au50 nanoparticles promoted the osteogenic differentiation of BMSCs in vitro. In addition, the overexpression of TREM2 in macrophage induced by Au50 nanoparticles was found to promote macrophage phagocytosis of Staphylococcus aureus, enhance the fusion of autophagosomes and lysosomes, accelerate the intracellular degradation of S. aureus, in addition to achieving an effective local treatment of osteomyelitis and infectious skin defects in conjunction with inflammatory regulation and accelerating bone regeneration. The findings, therefore, demonstrate that Au50 nanoparticles can be utilized as a promising nanomaterial for in vivo treatment of infections.

19.
J Nat Prod ; 86(6): 1487-1499, 2023 06 23.
Article in English | MEDLINE | ID: mdl-37291059

ABSTRACT

A preliminary phytochemical investigation on the 90% MeOH extract from the twigs and needles of the vulnerable conifer Keteleeria fortunei led to the isolation and characterization of 17 structurally diverse triterpen-26-oic acids, including nine previously undescribed ones (fortunefuroic acids A-I, 1-9) featuring a rare furoic acid moiety in the lateral chain. Among them, 1-5 are uncommon 9ßH-lanostane-type triterpenoic acids. Friedo-rearranged triterpenoids 6 and 7 feature a unique 17,14-friedo-lanostane skeleton, whereas 9 possesses a rare 17,13-friedo-cycloartane-type framework. Their structures and absolute configurations were elucidated by extensive spectroscopic (e.g., detailed 2D NMR) and computational (NMR/ECD) calculations and the modified Mosher's method. In addition, the absolute structure of compound 1 was ascertained by single-crystal X-ray diffraction analyses. Fortunefuroic acids B (2), G (7), and I (9), along with isomangiferolic acid (12) and 3α,27-dihydroxycycloart-24E-en-26-oic acid (14), exhibited dual inhibitory effects against the adenosine triphosphate (ATP)-citrate lyase (ACL, IC50s: 5.7-11.4 µM) and acetyl-CoA carboxylase 1 (ACC1, IC50s: 7.5-10.5 µM), both of which are key enzymes for glycolipid metabolism. The interactions of the bioactive triterpenoids with both enzymes were examined by molecular docking studies. The above findings reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics for ACL-/ACC1-associated diseases.


Subject(s)
Abies , Tracheophyta , Triterpenes , Molecular Docking Simulation , Triterpenes/chemistry , Abies/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure
20.
BMC Plant Biol ; 23(1): 248, 2023 May 11.
Article in English | MEDLINE | ID: mdl-37170202

ABSTRACT

BACKGROUND: Histone modification is an important epigenetic regulatory mechanism and essential for stress adaptation in plants. However, systematic analysis of histone modification genes (HMs) in Brassicaceae species is lacking, and their roles in response to abiotic stress have not yet been identified. RESULTS: In this study, we identified 102 AtHMs, 280 BnaHMs, 251 BcHMs, 251 BjHMs, 144 BnHMs, 155 BoHMs, 137 BrHMs, 122 CrHMs, and 356 CsHMs in nine Brassicaceae species, respectively. Their chromosomal locations, protein/gene structures, phylogenetic trees, and syntenies were determined. Specific domains were identified in several Brassicaceae HMs, indicating an association with diverse functions. Syntenic analysis showed that the expansion of Brassicaceae HMs may be due to segmental and whole-genome duplications. Nine key BnaHMs in allotetraploid rapeseed may be responsible for ammonium, salt, boron, cadmium, nitrate, and potassium stress based on co-expression network analysis. According to weighted gene co-expression network analysis (WGCNA), 12 BnaHMs were associated with stress adaptation. Among the above genes, BnaPRMT11 simultaneously responded to four different stresses based on differential expression analysis, while BnaSDG46, BnaHDT10, and BnaHDA1 participated in five stresses. BnaSDG46 was also involved in four different stresses based on WGCNA, while BnaSDG10 and BnaJMJ58 were differentially expressed in response to six different stresses. In summary, six candidate genes for stress resistance (BnaPRMT11, BnaSDG46, BnaSDG10, BnaJMJ58, BnaHDT10, and BnaHDA1) were identified. CONCLUSIONS: Taken together, these findings help clarify the biological roles of Brassicaceae HMs. The identified candidate genes provide an important reference for the potential development of stress-tolerant oilseed plants.


Subject(s)
Brassica napus , Brassica rapa , Brassica napus/genetics , Brassica napus/metabolism , Phylogeny , Histone Code/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Brassica rapa/genetics , Stress, Physiological/genetics , Gene Expression Regulation, Plant
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