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1.
Plant Cell ; 35(7): 2654-2677, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37043544

RESUMO

Cellulose, the main component of the plant cell wall, is synthesized by the multimeric cellulose synthase (CESA) complex (CSC). In plant cells, CSCs are assembled in the endoplasmic reticulum or Golgi and transported through the endomembrane system to the plasma membrane (PM). However, how CESA catalytic activity or conserved motifs around the catalytic core influence vesicle trafficking or protein dynamics is not well understood. Here, we used yellow fluorescent protein (YFP)-tagged AtCESA6 and created 18 mutants in key motifs of the catalytic domain to analyze how they affected seedling growth, cellulose biosynthesis, complex formation, and CSC dynamics and trafficking in Arabidopsis thaliana. Seedling growth and cellulose content were reduced by nearly all mutations. Moreover, mutations in most conserved motifs slowed CSC movement in the PM as well as delivery of CSCs to the PM. Interestingly, mutations in the DDG and QXXRW motifs affected YFP-CESA6 abundance in the Golgi. These mutations also perturbed post-Golgi trafficking of CSCs. The 18 mutations were divided into 2 groups based on their phenotypes; we propose that Group I mutations cause CSC trafficking defects, whereas Group II mutations, especially in the QXXRW motif, affect protein folding and/or CSC rosette formation. Collectively, our results demonstrate that the CESA6 catalytic domain is essential for cellulose biosynthesis as well as CSC formation, protein folding and dynamics, and vesicle trafficking.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Domínio Catalítico , Mutação Puntual , Arabidopsis/genética , Arabidopsis/metabolismo , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Parede Celular/metabolismo , Plântula/metabolismo , Celulose/metabolismo
2.
Mol Med ; 30(1): 60, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750415

RESUMO

Severe acute pancreatitis (SAP) begins with premature activation of enzymes, promoted by the immune system, triggering a potential systemic inflammatory response that leads to organ failure with increased mortality and a bleak prognosis. Interleukin-22 (IL-22) is a cytokine that may have a significant role in SAP. IL-22, a member of the IL-10 cytokine family, has garnered growing interest owing to its potential tissue-protective properties. Recently, emerging research has revealed its specific effects on pancreatic diseases, particularly SAP. This paper provides a review of the latest knowledge on the role of IL-22 and its viability as a therapeutic target in SAP.


Assuntos
Interleucina 22 , Interleucinas , Pancreatite , Humanos , Interleucinas/metabolismo , Pancreatite/metabolismo , Pancreatite/imunologia , Animais , Doença Aguda
3.
J Cell Sci ; 135(7)2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35194638

RESUMO

Multicellular organisms use dedicator of cytokinesis (DOCK) family guanine nucleotide exchange factors (GEFs) to activate Rac/Rho-of-plants small GTPases and coordinate cell shape change. In developing tissues, DOCK signals integrate cell-cell interactions with cytoskeleton remodeling, and the GEFs cluster reversibly at specific organelle surfaces to orchestrate cytoskeletal reorganization. The domain organizations among DOCK orthologs are diverse, and the mechanisms of localization control are poorly understood. Here, we use combinations of transgene complementation and live-cell imaging assays to uncover an evolutionarily conserved and essential localization determinant in the DOCK-GEF named SPIKE1. The SPIKE1-DHR3 domain is sufficient for organelle association in vivo, and displays a complicated lipid-binding selectivity for both phospholipid head groups and fatty acid chain saturation. SPIKE1-DHR3 is predicted to adopt a C2-domain structure and functions as part of a tandem C2 array that enables reversible clustering at the cell apex. This work provides mechanistic insight into how DOCK GEFs sense compositional and biophysical membrane properties at the interface of two organelle systems.


Assuntos
Fatores de Troca do Nucleotídeo Guanina , Proteínas Monoméricas de Ligação ao GTP , Domínios C2 , Citocinese , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Organelas/metabolismo
4.
Small ; : e2401551, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39109958

RESUMO

Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing the viable treatment needs across different healing stages is a critical challenge in wound management. Herein, a novel core-shell microneedle (CSMN) patch is designed for the sequential delivery of tannic acid-magnesium (TA-Mg) complexes and extracellular vesicles from Lactobacillus druckerii (LDEVs). Upon application to infected sites, CSMN@TA-Mg/LDEV releases TA-Mg first to counteract pathogenic overload and reduce reactive oxygen species (ROS), aiding the transition to proliferative phase. Subsequently, the sustained release of LDEVs enhances the activities of keratinocytes and fibroblasts, promotes vascularization, and modulates the collagen deposition. Notably, dynamic track of microbial composition demonstrates that CSMN@TA-Mg/LDEV can both inhibit the aggressive pathogen and increase the microbial diversity at wound sites. Functional analysis further highlights the potential of CSMN@TA-Mg/LDEV in facilitating wound healing and skin barrier restoration. Moreover, it is confirmed that CSMN@TA-Mg/LDEV can accelerate wound closure and improve post-recovery skin quality in the murine infected wound. Conclusively, this innovative CSMN patch offers a rapid and high-quality alternative treatment for infected wounds and emphasizes the significance of microbial homeostasis.

5.
Plant Cell ; 33(7): 2454-2478, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-33871640

RESUMO

Myosin motors are essential players in secretory vesicle trafficking and exocytosis in yeast and mammalian cells; however, similar roles in plants remain a matter for debate, at least for diffusely growing cells. Here, we demonstrate that Arabidopsis (Arabidopsis thaliana) myosin XIK, via its globular tail domain (GTD), participates in the vesicle tethering step of exocytosis through direct interactions with the exocyst complex. Specifically, myosin XIK GTD bound directly to several exocyst subunits in vitro and functional fluorescently tagged XIK colocalized with multiple exocyst subunits at plasma membrane (PM)-associated stationary foci. Moreover, genetic and pharmacological inhibition of myosin XI activity reduced the rate of appearance and lifetime of stationary exocyst complexes at the PM. By tracking single exocytosis events of cellulose synthase (CESA) complexes with high spatiotemporal resolution imaging and pair-wise colocalization of myosin XIK, exocyst subunits, and CESA6, we demonstrated that XIK associates with secretory vesicles earlier than exocyst and is required for the efficient localization and normal dynamic behavior of exocyst complex at the PM tethering site. This study reveals an important functional role for myosin XI in secretion and provides insights about the dynamic regulation of exocytosis in plants.


Assuntos
Arabidopsis/metabolismo , Citoplasma/metabolismo , Membrana Celular/metabolismo , Glucosiltransferases/metabolismo , Vesículas Secretórias/metabolismo
6.
Chemistry ; : e202402581, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143837

RESUMO

Metal-organic frameworks (MOFs) show potential application in many domains, in which photochromic MOFs (PMOFs) have received enormous attention. Researchers mainly utilize photoactive ligands to build PMOFs. Recently, the mixed electron donating and accepting ligands strategies have also been used to construct PMOFs driven by the electron transfer between nonphotochromic moieties. However, the potential interligand competition inhibits the formation of PMOFs. Therefore, the exploration of single-ligand-guided assembly is conductive for building PMOFs. Considering the existing electron accepting and donating role of pyridyl and carboxyl, the pyridinecarboxyate derived from the fusion of pyridyl and carboxyl units may serve as single ligand to yield PMOFs. In this work, the coordination assembly of bipyridinedicarboxylate (2,2'-bipyridine-4,4'-dicarboxylic acid, H2bpdc; 1,10-phenanthroline-2,9-dicarboxylic acid, H2pda) and LaCl3 generate two PMOFs, [La(bpdc)(H2O)Cl] (1) and [La(pda)(H2O)2Cl]·2H2O (2). Both complexes feature dinuclear lanthanum as building blocks with differences in the connecting number of likers, in which 1 has (4,8)-connected topology and 2 exhibits sql topology. Their structural differences result in the diversities of photoresponsive functionalities. Compared with reported PMOFs built from photoactive ligands and mixed ligands, this study provides new available categories of single ligand for generating PMOFs and tuning the structure and photoresponsive properties via ligand substitution and external photostimulus.

7.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 140-146, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38678618

RESUMO

The incidence and mortality of endometrial carcinoma (EC) are increasing year by year. Although the curative effect of surgery and commonly used drugs is clear, it is accompanied by obvious side effects, and safe and effective means are urgently needed to promote the curative effect and decrease the toxicity of drugs. Traditional Chinese medicine has been passed down for thousands of years in China and has proved to be advantageous in the treatment of various cancers and the auxiliary enhancement and reduction of toxicity. This paper reviewed the role and internal mechanism of Salvia miltiorrhiza in preventing and treating endometrial carcinoma by referring to relevant literature and works, so as to more comprehensively understand and grasp the research status, effective components, curative effect and effective mechanism of S. miltiorrhiza in preventing and treating endometrial carcinoma, and provide ideas and basis for clinical use and basic research.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias do Endométrio , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Humanos , Feminino , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos
8.
J Environ Manage ; 366: 121792, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39002459

RESUMO

Signal transduction is an important mode of algae-bacteria interaction, in which bacterial quorum sensing (QS) may affect microalgal growth and metabolism. Currently, little is known whether acyl homoserine lactones (AHLs) released by bacteria can affect the pollutant removal by algae-bacteria consortia (ABC). In this study, we constructed ABC using Chlorella vulgaris (Cv) with two AHLs-producing bacteria and investigated their performance in the removal of multiple pollutants, including chemical oxygen demand (COD), total nitrogen (TN), phosphorus (P), and cadmium (Cd). The AHLs-producing bacteria, namely Agrobacterium sp. (Ap) and Ensifer adherens (Ea), were capable of forming a symbiosis with C. vulgaris. Consortia of Cv and Ap with ratio of 2:1 (Cv2-Ap1) showed the optimal growth promotion and higher removal of Cd, COD, TN, and P compared to the C. vulgaris monoculture. Cv2-Ap1 ABC removed 36.1-47.5% of Cd, 94.5%-94.6% COD, 37.1%-56.0% TN, and 90.4%-93.5% P from the culture medium. In addition, increase of intracellular neutral lipids and extracellular protein, as well as the types of functional groups on cell surface contributed to Cd removal and tolerance in the Cv2-Ap1 ABC. Six AHLs were detected in the Cv2-Ap1 culture. Among these, 3OC8-HSL and 3OC12-HSL additions promoted the ABC growth and enhanced their Cd accumulation. These findings may contribute to further understanding of AHL-mediated communication between algae and bacteria and provide support bioremediation efforts of metal-containing wastewater.


Assuntos
Acil-Butirolactonas , Cádmio , Cádmio/metabolismo , Acil-Butirolactonas/metabolismo , Chlorella vulgaris/metabolismo , Chlorella vulgaris/crescimento & desenvolvimento , Bactérias/metabolismo , Biodegradação Ambiental , Percepção de Quorum , Fósforo/metabolismo , Nitrogênio/metabolismo
9.
Molecules ; 29(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731439

RESUMO

The production of peanut oil in the industrial sector necessitates the utilization of diverse raw materials to generate consistent batches with stable flavor profiles, thereby leading to an increased focus on understanding the correlation between raw materials and flavor characteristics. In this study, sensory evaluations, headspace solid-phase micro-extraction gas chromatography mass spectrometry (HS-SPME-GC-MS), odor activity value (OAV) calculations, and correlation analysis were employed to investigate the flavors and main contributing amino acids of hot-pressed oils derived from different peanut varieties. The results confirmed that the levels of alcohols, aldehydes, and heterocyclic compounds in peanut oil varied among nine different peanut varieties under identical processing conditions. The OAVs of 25 key aroma compounds, such as methylthiol, 3-ethyl-2,5-dimethylpyrazine, and 2,3-glutarone, exceeded a value of 1. The sensory evaluations and flavor content analysis demonstrated that pyrazines significantly influenced the flavor profile of the peanut oil. The concentrations of 11 amino acids showed a strong correlation with the levels of pyrazines. Notably, phenylalanine, lysine, glutamic acid, arginine, and isoleucine demonstrated significant associations with both pyrazine and nut flavors. These findings will provide valuable insights for enhancing the sensory attributes of peanut oil and selecting optimal raw peanuts for its production.


Assuntos
Aminoácidos , Arachis , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Óleo de Amendoim , Aminoácidos/análise , Aminoácidos/química , Arachis/química , Odorantes/análise , Óleo de Amendoim/química , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Aromatizantes/química , Aromatizantes/análise , Pirazinas/química , Pirazinas/análise , Microextração em Fase Sólida , Paladar , Temperatura Alta
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(6): 696-701, 2024 Jun 10.
Artigo em Zh | MEDLINE | ID: mdl-38818553

RESUMO

OBJECTIVE: To explore the feasibility of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal copy number variants (CNV). METHODS: A retrospective analysis was carried out on NIPT positive samples in Suzhou Municipal Hospital from January 1, 2019 to December 31, 2021. The effect of NIPT on fetal CNV detection was assessed by comparison with the results of karyotype analysis and/or chromosomal microarray analysis (CMA). RESULTS: Among the 525 NIPT positive samples, 146 were CNV cases, of which 84 were further verified by karyotyping and/or CMA, 29 (34.5%) were true positive. Among them, 12 cases were pathogenic variants, 2 cases were likely pathogenic variants and 15 cases were variants of uncertain significance. CONCLUSION: NIPT could detect CNV with high accuracy, and to combine CNV detection and chromosomal aneuploidy detection has great significance to improve the prenatal and postnatal care.


Assuntos
Variações do Número de Cópias de DNA , Cariotipagem , Teste Pré-Natal não Invasivo , Diagnóstico Pré-Natal , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Teste Pré-Natal não Invasivo/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Aneuploidia , Feto , Estudos de Viabilidade
11.
J Environ Sci (China) ; 146: 28-38, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38969456

RESUMO

Semiconductor heterojunction engineering and three-dimensional (3D) architecture construction have been considered highly desirable strategies to enhance photocatalytic performance. Herein, a BiOI/ZnO composite photocatalyst with a 3D flower-like architecture was successfully prepared, which was stably immobilized on three-dimensional porous lignocellulosic biomass Juncus effusus (JE) fiber. The outstanding photocatalytic performance of the BiOI/ZnO-JE fiber was confirmed by the degradation of tetracycline hydrochloride (TC, 90%), ciprofloxacin (CIP, 79%), and norfloxacin (NOR, 81%). The enhanced photocatalytic activities were mainly attributed to the synergistic absorption performance of the lignocellulosic JE and the effective transfer and separation of charges. Moreover, the hydroxyl (·OH) and superoxide radicals (·O2-) are the main reactive species in the photocatalytic process according to the analysis. This work may provide a novel perspective for constructing high-performance lignocellulosic-based photocatalytic materials.


Assuntos
Biomassa , Fotólise , Óxido de Zinco , Óxido de Zinco/química , Poluentes Químicos da Água/química , Catálise
12.
BMC Genomics ; 24(1): 514, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658288

RESUMO

BACKGROUND: The cellular and molecular dynamics of human prepuce are crucial for understanding its biological and physiological functions, as well as the prevention of related genital diseases. However, the cellular compositions and heterogeneity of human prepuce at single-cell resolution are still largely unknown. Here we systematically dissected the prepuce of children and adults based on the single-cell RNA-seq data of 90,770 qualified cells. RESULTS: We identified 15 prepuce cell subtypes, including fibroblast, smooth muscle cells, T/natural killer cells, macrophages, vascular endothelial cells, and dendritic cells. The proportions of these cell types varied among different individuals as well as between children and adults. Moreover, we detected cell-type-specific gene regulatory networks (GRNs), which could contribute to the unique functions of related cell types. The GRNs were also highly dynamic between the prepuce cells of children and adults. Our cell-cell communication network analysis among different cell types revealed a set of child-specific (e.g., CD96, EPO, IFN-1, and WNT signaling pathways) and adult-specific (e.g., BMP10, NEGR, ncWNT, and NPR1 signaling pathways) signaling pathways. The variations of GRNs and cellular communications could be closely associated with prepuce development in children and prepuce maintenance in adults. CONCLUSIONS: Collectively, we systematically analyzed the cellular variations and molecular changes of the human prepuce at single-cell resolution. Our results gained insights into the heterogeneity of prepuce cells and shed light on the underlying molecular mechanisms of prepuce development and maintenance.


Assuntos
Células Endoteliais , Regulação da Expressão Gênica , Adulto , Humanos , Comunicação Celular/genética , Redes Reguladoras de Genes , Análise de Célula Única , Proteínas Morfogenéticas Ósseas
13.
BMC Plant Biol ; 23(1): 663, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129812

RESUMO

BACKGROUND: Plant HSP20s are not only synthesized in response to heat stress but are also involved in plant biotic and abiotic stress resistance, normal metabolism, development, differentiation, survival, ripening, and death. Thus, HSP20 family genes play very important and diverse roles in plants. To our knowledge, HSP20 family genes in peach have not yet been characterized in detail, and little is known about their possible function in the development of red flesh in peach. RESULTS: In total, 44 PpHSP20 members were identified in the peach genome in this study. Forty-four PpHSP20s were classified into 10 subfamilies, CI, CII, CIII, CV, CVI, CVII, MII, CP, ER, and Po, containing 18, 2, 2, 10, 5, 1, 1, 2, 1, and 2 proteins, respectively. Among the 44 PpHSP20 genes, 6, 4, 4, 3, 7, 11, 5, and 4 PpHSP20 genes were located on chromosomes 1 to 8, respectively. In particular, approximately 15 PpHSP20 genes were located at both termini or one terminus of each chromosome. A total of 15 tandem PpHSP20 genes were found in the peach genome, which belonged to five tandemly duplicated groups. Overall, among the three cultivars, the number of PpHSP20 genes with higher expression levels in red flesh was greater than that in yellow or white flesh. The expression profiling for most of the PpHSP20 genes in the red-fleshed 'BJ' was higher overall at the S3 stage than at the S2, S4-1, and S4-2 stages, with the S3 stage being a very important period of transformation from a white color to the gradual anthocyanin accumulation in the flesh of this cultivar. The subcellular localizations of 16 out of 19 selected PpHSP20 proteins were in accordance with the corresponding subfamily classification and naming. Additionally, to our knowledge, Prupe.3G034800.1 is the first HSP20 found in plants that has the dual targets of both the endoplasmic reticulum and nucleus. CONCLUSIONS: This study provides a comprehensive understanding of PpHSP20s, lays a foundation for future analyses of the unknown function of PpHSP20 family genes in red-fleshed peach fruit and advances our understanding of plant HSP20 genes.


Assuntos
Prunus persica , Genoma de Planta , Genes de Plantas/genética , Resposta ao Choque Térmico , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Frutas/genética , Filogenia
14.
Plant Cell ; 32(7): 2141-2157, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32327535

RESUMO

Plant cellulose is synthesized by rosette-structured cellulose synthase (CESA) complexes (CSCs). Each CSC is composed of multiple subunits of CESAs representing three different isoforms. Individual CESA proteins contain conserved catalytic domains for catalyzing cellulose synthesis, other domains such as plant-conserved sequences, and class-specific regions that are thought to facilitate complex assembly and CSC trafficking. Because of the current lack of atomic-resolution structures for plant CSCs or CESAs, the molecular mechanism through which CESA catalyzes cellulose synthesis and whether its catalytic activity influences efficient CSC transport at the subcellular level remain unknown. Here, by performing chemical genetic analyses, biochemical assays, structural modeling, and molecular docking, we demonstrate that Endosidin20 (ES20) targets the catalytic site of CESA6 in Arabidopsis (Arabidopsis thaliana). Chemical genetic analysis revealed important amino acids that potentially participate in the catalytic activity of plant CESA6, in addition to previously identified conserved motifs across kingdoms. Using high spatiotemporal resolution live cell imaging, we found that inhibiting the catalytic activity of CESA6 by ES20 treatment reduced the efficiency of CSC transport to the plasma membrane. Our results demonstrate that ES20 is a chemical inhibitor of CESA activity and trafficking that represents a powerful tool for studying cellulose synthesis in plants.


Assuntos
Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Arabidopsis/efeitos dos fármacos , Celulose/biossíntese , Glucosiltransferases/antagonistas & inibidores , Glucosiltransferases/química , Glucosiltransferases/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Domínio Catalítico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Recuperação de Fluorescência Após Fotodegradação , Glucosiltransferases/genética , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Simulação de Acoplamento Molecular , Mutação , Plantas Geneticamente Modificadas , Conformação Proteica
15.
Crit Rev Food Sci Nutr ; 63(3): 303-329, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34254536

RESUMO

Alginates are linear polymers comprising 40% of the dry weight of algae possess various applications in food and biomedical industries. Alginate oligosaccharides (AOS), a degradation product of alginate, is now gaining much attention for their beneficial role in food, pharmaceutical and agricultural industries. Hence this review was aimed to compile the information on alginate and AOS (prepared from seaweeds) during 1994-2020. As per our knowledge, this is the first review on the potential use of alginate oligosaccharides in different fields. The alginate derivatives are grouped according to their applications. They are involved in the isolation process and show antimicrobial, antioxidant, anti-inflammatory, antihypertension, anticancer, and immunostimulatory properties. AOS also have significant applications in prebiotics, nutritional supplements, plant growth development and others products.


Assuntos
Alginatos , Alga Marinha , Alginatos/metabolismo , Oligossacarídeos/metabolismo , Antioxidantes , Suplementos Nutricionais
16.
Cell Mol Life Sci ; 79(7): 360, 2022 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690642

RESUMO

Breast cancer stem cells (BCSCs) are positively correlated with the metastasis, chemoresistance, and recurrence of breast cancer. However, there are still no drugs targeting BCSCs in clinical using for breast cancer treatment. Here, we tried to screen out small-molecule compounds targeting BCSCs from the phenazine library established by us before. We focused on the compounds without affecting cell viability and screened out three potential compounds (CPUL119, CPUL129, CPUL149) that can significantly attenuate the stemness of breast cancer cells, as evident by the decrease of stemness marker expression, CD44+/CD24- subpopulation, mammary spheroid-formation ability, and tumor-initiating capacity. Additionally, these compounds suppressed the metastatic ability of breast cancer cells in vitro and in vivo. Combined with the transcriptome sequencing analysis, ferroptosis was shown on the top of the most upregulated pathways by CPUL119, CPUL129, and CPUL149, respectively. Mechanistically, we found that these three compounds could trigger ferroptosis by accumulating and sequestering iron in lysosomes through interacting with iron, and by regulating the expression of proteins (IRP2, TfR1, ferritin) engaged in iron transport and storage. Furthermore, inhibition of ferroptosis rescued the suppression of these three compounds on breast cancer cell stemness. This study suggests that CPUL119, CPUL129, and CPUL149 can specifically inhibit the stemness of breast cancer cells through triggering ferroptosis and may be the potential compounds for breast cancer treatment.


Assuntos
Neoplasias da Mama , Ferroptose , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Ferro/metabolismo , Células-Tronco Neoplásicas/metabolismo , Fenazinas/metabolismo , Fenazinas/farmacologia , Fenazinas/uso terapêutico
17.
Chem Biodivers ; 20(2): e202201117, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36536551

RESUMO

Thirty-seven novel chalcone-phenazine hybrid molecules (C1∼C13 and F1∼F24) with 1,2,3-triazole or ethyl group as linkers were designed and synthesized in this study. Some compounds exhibited selective cytotoxicity against U87-MG cancer cell lines in vitro, in which compound C4 were found to have the best antiproliferative activity. SAR study indicated 1,2,3-triazole group may be crucial for enhancing compounds' cytotoxicity. C4 was verified to induce ferroptosis in U87-MG cells by transcription, lipid peroxidation, lipid ROS assays. Furthermore, C4 was up-regulated LC3-II, degradated FTH1, and then increasing iron resulted in the down-regulation of NCOA4. Together, all above evidences highlighted the potential of compound C4 that triggered ferroptosis by activating ferritinophagy against U87-MG cells.


Assuntos
Chalcona , Chalconas , Ferroptose , Fenazinas , Triazóis , Autofagia
18.
J Adv Nurs ; 79(7): 2632-2642, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36896878

RESUMO

AIMS: To evaluate the features of depressive and anxiety symptoms and illness perception and their associations in patients with acute coronary syndrome (ACS). DESIGN: Secondary analysis of data from a cross-sectional study and baseline data from a randomized controlled trial. METHODS: From June to July 2019 and June to September 2020, patients with ACS in four public hospitals in China completed measurements of depressive and anxiety symptoms, illness perception, and sociodemographic and clinical characteristics. Data were analysed using univariate and multiple logistic regression analyses. RESULTS: This study included 510 participants (mean age, 61.0 ± 9.9 years; 67.8% male). The prevalence of depressive and anxiety symptoms was 66.3% and 56.5%, respectively. Total score of illness perception was 43.5 ± 9.1 and mean scores of each dimension ranged from 5.5 to 7.6, suggesting relatively negative illness perceptions. The top two perceived causes of illness were negative emotions or stress (27.3%) and dietary habits (25.5%) and 24.7% of participants were unaware of causes regarding their illness. After adjusting for potential confounders, a one-point increase in scores on illness perception regarding consequences and emotional response (range, 0-10) was related to a 22% increased probability of depressive symptoms. Every one-point increase in scores on illness perception related to emotional response, personal control and illness comprehensibility was associated with a 38% increased, 13% decreased and 9% decreased probability of anxiety symptoms, respectively. CONCLUSION: Depressive and anxiety symptoms are prevalent at high rates in patients with ACS. They have a relatively negative illness perception that is associated with the prevalence of depressive and anxiety symptoms. IMPACT: This study highlights the importance of screening for depressive and anxiety symptoms in patients with ACS, especially for those with negative illness perceptions. Targeted strategies are imperative to improve patients' health outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: These details do not apply to this work.


Assuntos
Síndrome Coronariana Aguda , Depressão , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Depressão/epidemiologia , Depressão/etiologia , Síndrome Coronariana Aguda/epidemiologia , Estudos Transversais , Ansiedade/etiologia , Percepção
19.
J Adv Nurs ; 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38041587

RESUMO

AIMS: Fear of cancer recurrence (FCR) is a multifaceted concept influenced by individual characteristics, social support, psychological factors. This study aims to identify distinct FCR profiles among breast cancer patients and explore the associated variables with these patterns. DESIGN: A cross-sectional study was conducted from April 2022 to March 2023. METHODS: A convenience sample of 339 patients completed a questionnaire that assessed general and disease-related data, including the Fear of Progression Questionnaire-Short Form, Social Support Rating Scale, Medical Coping Modes Questionnaire. Statistical analysis involved latent profile analysis (LPA) and multinomial logistic regression. RESULTS: Three latent patterns of FCR were found: the low fear (28.9%), the moderate fear (51.3%), and the high fear (18.0%). The study identified the social support, family monthly income, employment status, utilization of confrontation coping mode and avoidance coping mode, as factors that impacted the FCR. CONCLUSIONS: Social support, family monthly income, employment status, and medical coping modes have been found to impact the FCR among newly diagnosed breast cancer patients. Healthcare professionals should focus on addressing FCR at diagnosis and implement effective interventions, such as promoting social support and encouraging adaptive coping, to alleviate this concern. IMPACT: Urgently addressing the FCR in Chinese breast cancer patients is imperative due to its profound influence on their holistic health. Through advanced LPA, we categorized the FCR progression, highlighting risks. These findings have implications for healthcare strategies, offering new insights to manage the FCR and improve patient well-being. Our study adds a fresh perspective to the factors underlying the FCR in breast cancer patients, contributing to the broader comprehension and management of this complex survivorship issue. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

20.
Sensors (Basel) ; 23(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37112442

RESUMO

Ecosystem conditions at the regional level are critical factors for environmental management, public awareness, and land use decision making. Regional ecosystem conditions may be examined from the perspectives of ecosystem health, vulnerability, and security, as well as other conceptual frameworks. Vigor, organization, and resilience (VOR) and pressure-stress-response (PSR) are two commonly adopted conceptual models for indicator selection and organization. The analytical hierarchy process (AHP) is primarily used to determine model weights and indicator combinations. Although there have been many successful efforts in assessing regional ecosystems, they remain affected by a lack of spatially explicit data, weak integration of natural and human dimensions, and uncertain data quality and analyses. In the future, regional ecosystem condition assessments may be advanced by incorporating recent improvements in spatial big data and machine learning to create more operative indicators based on Earth observations and social metrics. The collaboration between ecologists, remote sensing scientists, data analysts, and scientists in other relevant disciplines is critical for the success of future assessments.

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