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1.
Plant Cell Environ ; 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39444137

RESUMEN

Root System Architecture (RSA) is a crucial plant trait that governs a plant's ability to absorb water and nutrients. In this study, we describe a mutant with nutrient-dependent defects in root development, affecting both the primary root and lateral roots (LRs). This mutant, identified through a screen for defects in LR development, has been designated dlr1-1. The dlr1-1 mutant exhibits impaired LR emergence rather than defects in the LR primordium (LRP) formation, particularly under potassium (K+)-deprivation conditions. This impairment likely stems from inhibited cell proliferation caused by the dlr1-1 mutation. K+ deprivation specifically leads to the accumulation of salicylic acid (SA) in the dlr1-1 mutant, consistent with the upregulation of SA biosynthesis genes. Moreover, exogenous application of SA to wild-type plants (B73) mimics the dlr1-1 phenotype. Conversely, treatment of the dlr1-1 mutant with 2-aminoindane-2-phosphonic acid, an SA biosynthesis inhibitor, partially restores LR emergence, indicating that elevated SA levels may be responsible for the mutant's developmental defects. MutMap analysis and allelism tests confirmed that the phenotypes of the dlr1-1 mutant results from the loss of the Na+/H+ antiporter, ZmNHX7. Additionally, the application of NaCl exacerbates the dlr1-1 mutant phenotype, suggesting that the root defects in dlr1-1 mutant depend on ion homoeostasis. In conclusion, our findings demonstrate that maize DLR1/NHX7 is essential for root development under potassium deprivation.

2.
Plant Cell Physiol ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39301683

RESUMEN

In Arabidopsis, RNA editing alters more than 500 cytidines (C) to uridines (U) in mitochondrial transcripts, a process involving the family of pentatricopeptide repeat (PPR) proteins. Here, we report a previously uncharacterized mitochondrial PLS-type PPR protein, GEND2, which functions in the mitochondrial RNA editing. The T-DNA insertion in the 5'-untranslated region of GEND2, referred to as gend2-1, results in defective root development compared to wild-type (WT) plants. A comprehensive examination of mitochondrial RNA editing sites revealed a significant reduction in the gend2-1 mutant compared to WT plants, affecting six specific mitochondrial RNA editing sites, notably within the mitochondrial genes CcmFn-1, RPSL2 and ORFX. These genes encode critical components of cytochrome protein maturation pathway, mitochondrial ribosomal subunit, and twin arginine translocation subunits, respectively. Further analysis of the transcriptional profile of the gend2-1 mutant and wild type revealed a striking induction of expression in a cluster of genes associated with mitochondrial dysfunction and regulated by ANAC017, a key regulator coordinating organelle functions and stress responses. Intriguingly, the gend2-1 mutation activated an ANAC017-dependent signaling aimed at countering cell wall damage induced by cellulose synthase inhibitors, as well as an ANAC017-independent pathway that retarded root growth under normal condition. Collectively, our findings identify a novel mitochondrial PLS-type PPR protein GEND2, which participates in the editing of six specific mitochondrial RNA editing sites. Furthermore, the gend2-1 mutation triggers two distinct pathways in plants: an ANAC017-dependent pathway and ANAC017-independent pathway.

3.
Nat Commun ; 15(1): 7696, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227617

RESUMEN

Heat stress (HS) poses a significant challenge to plant survival, necessitating sophisticated molecular mechanisms to maintain cellular homeostasis. Here, we identify SICKLE (SIC) as a key modulator of HS responses in Arabidopsis (Arabidopsis thaliana). SIC is required for the sequestration of RNA DEBRANCHING ENZYME 1 (DBR1), a rate-limiting enzyme of lariat intronic RNA (lariRNA) decay, into stress granules (SGs). The sequestration of DBR1 by SIC enhances the accumulation of lariRNAs, branched circular RNAs derived from excised introns during pre-mRNA splicing, which in turn promote the transcription of their parental genes. Our findings further demonstrate that SIC-mediated DBR1 sequestration in SGs is crucial for plant HS tolerance, as deletion of the N-terminus of SIC (SIC1-244) impairs DBR1 sequestration and compromises plant response to HS. Overall, our study unveils a mechanism of transcriptional regulation in the HS response, where lariRNAs are enriched through DBR1 sequestration, ultimately promoting the transcription of heat stress tolerance genes.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico , Intrones , Empalme del ARN , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Respuesta al Choque Térmico/genética , Intrones/genética , Gránulos de Estrés/metabolismo , Gránulos de Estrés/genética , ARN de Planta/metabolismo , ARN de Planta/genética , Termotolerancia/genética , ARN Circular/metabolismo , ARN Circular/genética , Plantas Modificadas Genéticamente
4.
Plant J ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115043

RESUMEN

The biogenesis of functional forms of chloroplast ribosomal RNAs (rRNAs) is crucial for the translation of chloroplast mRNAs into polypeptides. However, the molecular mechanisms underlying the proper processing and maturation of chloroplast rRNA species are poorly understood. Through a genetic approach, we isolated and characterized an Arabidopsis mutant, α1-4, harboring a missense mutation in the plastid chaperonin-60α1 gene. Using allelism tests and transgenic manipulation, we determined functional redundancy among ptCPN60 subunits. The ptCPN60α1S57F mutation caused specific defects in the formation of chloroplast rRNA species, including 23S, 5S, and 4.5S rRNAs, but not 16S rRNAs. Allelism tests suggested that the dysfunctional ptCPN60α1S57F competes with other members of the ptCPN60 family. Indeed, overexpression of the ptCPN60α1S57F protein in wild-type plants mimicked the phenotypes observed in the α1-4 mutant, while increasing the endogenous transcriptional levels of ptCPN60α2, ß1, ß2, and ß3 in the α1-4 mutant partially mitigated the abnormal fragmentation processing of chloroplast 23S, 5S, and 4.5S rRNAs. Furthermore, we demonstrated functional redundancy between ptCPN60ß1 and ptCPN60ß2 in chloroplast rRNA processing through double-mutant analysis. Collectively, our data reveal a novel physiological role of ptCPN60 subunits in generating the functional rRNA species of the large 50S ribosomal subunit in Arabidopsis chloroplasts.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124479, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-38772178

RESUMEN

Nowadays, it has been proven that lipid droplets (LDs) not only maintain the fundamental cellular functions, but also play an essential role in the pathogenesis of numerous diseases. Non-alcoholic fatty liver disease (NAFLD) is among these diseases. In this work, we designed two polarity sensitive fluorescent probes TST and TSO with D-π-A-D structure by introducing different electron acceptor groups according to the low polarity of LDs. The experimental discovered that probe TST exhibited the characteristics of near-infrared emission, high selectivity towards polarity, large Stokes shift, rapid targeting ability of LDs, and robust wash-free biological imaging capability. Confocal images illustrated that probe TST has been successfully applied in monitoring LDs polarity during ferroptosis, as well as visualizing changes in LDs polarity at both tissue and organ levels in fatty liver conditions. With these exceptional properties, probe TST was anticipated to make further contributions to the field of LDs research.


Asunto(s)
Colorantes Fluorescentes , Gotas Lipídicas , Enfermedad del Hígado Graso no Alcohólico , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Gotas Lipídicas/química , Colorantes Fluorescentes/química , Humanos , Animales , Diagnóstico Precoz , Ratones , Ratones Endogámicos C57BL , Masculino , Espectroscopía Infrarroja Corta/métodos , Imagen Óptica
6.
Food Chem ; 446: 138866, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38430769

RESUMEN

Fresh-cut potatoes are prone to surface browning and physiological degradation. Chlorogenic acid (CGA), a natural phenolic antioxidant, has demonstrated preservative properties in various postharvest products. However, the underlying mechanisms of its application on maintaining quality remain unclear. Therefore, the effect of exogenous CGA treatment on quality deterioration of potato slices and the mechanisms involved were investigated. Results revealed CGA treatment retarded the browning coloration, suppressed microbial growth and inhibited the declines in starch, and ascorbic acid contents in potato slices. Meanwhile, the treatment activated the phenylpropanoid pathway but decreased the activities of phenolic decomposition-related enzymes such as polyphenol oxidase (PPO) and tyrosinase and downregulated StPPO expression. Moreover, the treated slices exhibited reduced accumulation of reactive oxygen species and increased activity of antioxidant enzymes. Additionally, they displayed enhanced 2,2-diphenyl-1-picrylhydrazyl radicals scavenging capacity and higher ATP levels. Therefore, these findings indicated that CGA treatment was effective for quality maintenance and antioxidant capacity enhancement in fresh-cut potatoes, thereby providing potential strategies for the preservation and processing of fresh-cut produce.


Asunto(s)
Antioxidantes , Solanum tuberosum , Antioxidantes/metabolismo , Ácido Clorogénico/farmacología , Ácido Clorogénico/metabolismo , Solanum tuberosum/metabolismo , Fenoles/metabolismo , Ácido Ascórbico/metabolismo , Catecol Oxidasa/metabolismo
7.
Nat Commun ; 15(1): 170, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167652

RESUMEN

Practical photodynamic therapy calls for high-performance, less O2-dependent, long-wavelength-light-activated photosensitizers to suit the hypoxic tumor microenvironment. Iridium-based photosensitizers exhibit excellent photocatalytic performance, but the in vivo applications are hindered by conventional O2-dependent Type-II photochemistry and poor absorption. Here we show a general metallopolymerization strategy for engineering iridium complexes exhibiting Type-I photochemistry and enhancing absorption intensity in the blue to near-infrared region. Reactive oxygen species generation of metallopolymer Ir-P1, where the iridium atom is covalently coupled to the polymer backbone, is over 80 times higher than that of its mother polymer without iridium under 680 nm irradiation. This strategy also works effectively when the iridium atom is directly included (Ir-P2) in the polymer backbones, exhibiting wide generality. The metallopolymer nanoparticles exhibiting efficient O2•- generation are conjugated with integrin αvß3 binding cRGD to achieve targeted photodynamic therapy.


Asunto(s)
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/química , Iridio/química , Hipoxia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Polímeros/uso terapéutico , Microambiente Tumoral
8.
Adv Colloid Interface Sci ; 322: 103037, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37931381

RESUMEN

Inspired by natural catalytic compartments, various synthetic compartments that seclude catalytic reactions have been developed to understand complex multistep biosynthetic pathways, bestow therapeutic effects, or extend biosynthetic pathways in living cells. These emerging nanoreactors possessed many advantages over conventional biomedicine, such as good catalytic activity, specificity, and sustainability. In the past decade, a great number of efficient catalytic systems based on diverse nanoreactors (polymer vesicles, liposome, polymer micelles, inorganic-organic hybrid materials, MOFs, etc.) have been designed and employed to initiate in situ catalyzed chemical reactions for therapy. This review aims to present the recent progress in the development of catalytic systems based on nanoreactors for therapeutic applications, with a special emphasis on the principles and design strategies. Besides, the key components of nanoreactor-based catalytic systems, including nanocarriers, triggers or energy inputs, and products, are respectively introduced and discussed in detail. Challenges and prospects in the fabrication of therapeutic catalytic nanoreactors are also discussed as a conclusion to this review. We believe that catalytic nanoreactors will play an increasingly important role in modern biomedicine, with improved therapeutic performance and minimal side effects.


Asunto(s)
Liposomas , Polímeros , Catálisis , Micelas , Nanotecnología
9.
Cancer Res ; 83(15): 2614-2633, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37227919

RESUMEN

Cancer metastasis is an extremely complex process affected by many factors. An acidic microenvironment can drive cancer cell migration toward blood vessels while also hampering immune cell activity. Here, we identified a mechanism mediated by sialyltransferases that induces an acidic tumor-permissive microenvironment (ATPME) in BRCA1-mutant and most BRCA1-low breast cancers. Hypersialylation mediated by ST8SIA4 perturbed the mammary epithelial bilayer structure and generated an ATPME and immunosuppressive microenvironment with increased PD-L1 and PD1 expressions. Mechanistically, BRCA1 deficiency increased expression of VEGFA and IL6 to activate TGFß-ST8SIA4 signaling. High levels of ST8SIA4 led to accumulation of polysialic acid (PSA) on mammary epithelial membranes that facilitated escape of cancer cells from immunosurveillance, promoting metastasis and resistance to αPD1 treatment. The sialyltransferase inhibitor 3Fax-Peracetyl Neu5Ac neutralized the ATPME, sensitized cancers to immune checkpoint blockade by activating CD8 T cells, and inhibited tumor growth and metastasis. Together, these findings identify a potential therapeutic option for cancers with a high level of PSA. SIGNIFICANCE: BRCA1 deficiency generates an acidic microenvironment to promote cancer metastasis and immunotherapy resistance that can be reversed using a sialyltransferase inhibitor.


Asunto(s)
Neoplasias de la Mama , Microambiente Tumoral , Humanos , Femenino , Inmunoterapia , Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Sialiltransferasas/genética , Línea Celular Tumoral , Proteína BRCA1/genética
10.
J Am Chem Soc ; 145(24): 13099-13113, 2023 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-37216494

RESUMEN

Photosensitizers to precise target and change fluorescence upon light illumination could accurately self-report where and when the photosensitizers work, enabling us to visualize the therapeutic process and precisely regulate treatment outcomes, which is the unremitting pursuit of precision and personalized medicine. Here, we report self-immolative photosensitizers by adopting a strategy of light-manipulated oxidative cleavage of C═C bonds that can generate a burst of reactive oxygen species, to cleave to release self-reported red-emitting products and trigger nonapoptotic cell oncosis. Strong electron-withdrawing groups are found to effectively suppress the C═C bond cleavage and phototoxicity via studying the structure-activity relationship, allowing us to elaborate NG1-NG5 that could temporarily inactivate the photosensitizer and quench the fluorescence by different glutathione (GSH)-responsive groups. Thereinto, NG2 with 2-cyano-4-nitrobenzene-1-sulfonyl group displays excellent GSH responsiveness than the other four. Surprisingly, NG2 shows better reactivity with GSH in weakly acidic condition, which inspires the application in weakly acidic tumor microenvironment where GSH elevates. To this end, we further synthesize NG-cRGD by anchoring integrin αvß3 binding cyclic pentapeptide (cRGD) for tumor targeting. In A549 xenografted tumor mice, NG-cRGD successfully deprotects to restore near-infrared fluorescence because of elevated GSH in tumor site, which is subsequently cleaved upon light irradiation releasing red-emitting products to report photosensitizer working, while effectively ablating tumors via triggered oncosis. The advanced self-immolative organic photosensitizer may accelerate the development of self-reported phototheranostics in future precision oncology.


Asunto(s)
Nanopartículas , Neoplasias , Fotoquimioterapia , Ratones , Animales , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Neoplasias/tratamiento farmacológico , Autoinforme , Medicina de Precisión , Glutatión/química , Línea Celular Tumoral , Nanopartículas/química , Microambiente Tumoral
11.
Talanta ; 259: 124494, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37004395

RESUMEN

Mercury ion (Hg2+), as one of the most poisonous heavy metal ions, could seriously damage mental and neurological functions thus causing severe diseases. A fluorescent ratiometric sensor based on semiconducting polymer dots (Pdots) and rhodamine spirolactam derivate was developed for the detection of Hg2+. The Pdots were prepared by Poly [(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-diphenylene-vinylene-2-methoxy-5-{2-ethylhexyloxy}-benzene)] (PDDB) with emitting strong green fluorescence. The organic fluorescence dye N-(rhodamine-B) lactam-hydrazine (RhBH), as Hg2+-recognizing monomer, was conjugated to the surface of Pdots. Hg2+ could specifically trigger ring-opening process of RhBH and thus induce strong Förster resonance energy transfer (FRET) effect, resulting in the green fluorescence decrease of Pdots (energy donor) and red emission derived from the ring-opened RhBH (energy acceptor) increasing. PDDB@RhBH showed a sensitive and reversible response toward Hg2+ and had a great performance on resisting interferences from various biological analytes. Additionally, both fluorescent imaging in living cells and zebrafish, and systemic toxicity analysis in rats demonstrated that PDDB@RhBH was a great potential fluorescent sensor for quantitative Hg2+ imaging in living systems.


Asunto(s)
Colorantes Fluorescentes , Mercurio , Ratas , Animales , Polímeros , Mercurio/análisis , Pez Cebra , Rodaminas , Transferencia Resonante de Energía de Fluorescencia/métodos , Iones
12.
Pharmaceutics ; 15(2)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36839992

RESUMEN

Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and mßCD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.

13.
Plant J ; 114(1): 96-109, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36705084

RESUMEN

Ribosome biogenesis is a process of making ribosomes that is tightly linked with plant growth and development. Here, through a suppressor screen for the smo2 mutant, we found that lack of a ribosomal stress response mediator, ANAC082 partially restored growth defects of the smo2 mutant, indicating SMO2 is required for the repression of nucleolar stress. Consistently, the smo2 knock-out mutant exhibited typical phenotypes characteristic of ribosome biogenesis mutants, such as pointed leaves, aberrant leaf venation, disrupted nucleolar structure, abnormal distribution of rRNA precursors, and enhanced tolerance to aminoglycoside antibiotics that target ribosomes. SMO2 interacted with ROOT INITIATION DEFECTIVE 2 (RID2), a methyltransferase-like protein required for pre-rRNA processing. SMO2 enhanced RID2 solubility in Escherichia coli and the loss of function of SMO2 in plant cells reduced RID2 abundance, which may result in abnormal accumulation of FIBRILLARIN 1 (FIB1) and NOP56, two key nucleolar proteins, in high-molecular-weight protein complex. Taken together, our results characterized a novel plant ribosome biogenesis factor, SMO2 that maintains the abundance of RID2, thereby sustaining ribosome biogenesis during plant organ growth.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Nucléolo Celular/genética , Plantas/metabolismo , Ribosomas/metabolismo , ARN Ribosómico/genética , ARN Ribosómico/metabolismo
14.
BMC Public Health ; 22(1): 2012, 2022 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-36324106

RESUMEN

BACKGROUND: Brazil, China, Kazakhstan, and Russia are the main asbestos-producing countries, and all forms of asbestos are carcinogenic to humans. The objective of this study was to estimate the disease burden attributable to asbestos between 1990 and 2019 in major producing countries, including Brazil, China, Kazakhstan, and Russia. METHODS: Age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life year (DALY) rates (ASDR) of disease burden attributable to asbestos by country, age, and sex were extracted from the Global Burden of Disease 2019. Percentage change and estimated annual percentage change (EAPC) were used to assess the trends of ASDR and ASMR of disease burden attributable to asbestos between 1990 and 2019. RESULTS: Asbestos-related diseases were highly heterogeneous across Global, Brazil, China, Kazakhstan, and Russia. There was a downward trend in ASMR and ASDR of diseases burden related to asbestos globally. The age-specific mortality rate of disease attributable to asbestos increased in men and women, although it decreased in women aged 85-89, the highest age-specific mortality rate were observed in age 95 + group in men [162.14 (95% UI: 103.76-215.45)] and women [30.58 (95% UI: 14.83-44.33)] per 100 000 population, respectively. Tracheal, bronchus, and lung (TBL) cancer was the leading cause of death and DALYS attributable to asbestos between 1990 and 2019 globally and in Brazil, China, Kazakhstan, and Russia. China had the highest percentage change (73.31%) and EAPC [3.41 (95% CI: 2.75-4.08)] in ASMR related to exposure to asbestos in men, with the highest percentage change (73.31%) and EAPC [3.41 (95% CI: 2.75-4.08)] in ASDR in men. CONCLUSIONS: The ASMR and ASDR of disease burden attributable to asbestos decreased between 1990 and 2019 globally. TBL cancer was the leading cause of death and DALYs attributable to asbestos between 1990 and 2019. There has been an increasing trend in mortality and DALYs globally, especially in older men. The burden of disease attributable to asbestos is increasing in China, especially in men.


Asunto(s)
Amianto , Neoplasias , Masculino , Humanos , Femenino , Anciano , Años de Vida Ajustados por Calidad de Vida , Brasil , Kazajstán/epidemiología , Salud Global , China/epidemiología , Costo de Enfermedad , Amianto/toxicidad , Neoplasias/epidemiología , Carga Global de Enfermedades
15.
Biosensors (Basel) ; 12(9)2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36140081

RESUMEN

A reversible pH-responsive fluorescent probe, BP, was rationally designed and synthesized, based on protonation and deprotonation gave rise to oxazolidine ring open and close. The fluorescence response of BP against pH ranges from 3.78 to 7.54, which is suitable for labeling intracellular pH-dependent organelles. BP displayed strong red emission at a relatively high pH in living HeLa cells and U87 cells. More importantly, this probe exhibited good colocalization with both mitochondria and lysosomes in these two cell lines, attributing to pH-induced structure tautomerism resulting in an oxazolidine ring open and close that triggered effective targeting of these two organelles. As organelle interactions are critical for cellular processes, this strategy of targeting dual organelles through the structure tautomerism is conducive to further developing more effective and advanced probes for real-time imaging of the interaction between mitochondria and lysosomes.


Asunto(s)
Colorantes Fluorescentes , Orgánulos , Colorantes Fluorescentes/química , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Orgánulos/química , Oxazoles
16.
Biosensors (Basel) ; 12(9)2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-36140101

RESUMEN

Sulfur dioxide (SO2) and formaldehyde (FA) are important species that maintain redox homeostasis in life and are closely related to many physiological and pathological processes. Therefore, it is of great significance to realize the reversible monitoring of them at the intracellular level. Here, we synthesized a reversible ratiometric fluorescent probe through a reasonable design, which can sensitively monitor SO2 derivatives and FA, and the detection limit can reach 0.16 µM. The probe can specifically target mitochondria and successfully monitor the fluctuations of SO2 and FA in living cells. It also works well in the detection of SO2 and FA in zebrafish. This high-performance probe is expected to find broad in vitro and in vivo applications.


Asunto(s)
Colorantes Fluorescentes , Dióxido de Azufre , Animales , Transferencia Resonante de Energía de Fluorescencia , Formaldehído , Células HeLa , Humanos , Mitocondrias , Pez Cebra
17.
J Mater Chem B ; 10(33): 6307-6314, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35916051

RESUMEN

The development of high-performance photosensitizers is the top priority in photodynamic therapy (PDT). Iridium complexes are widely used because of their many advantages such as high photostability, long T1 lifetime, high yield of singlet oxygen generation, and so on. Halogen-bridged binuclear complexes are often used as intermediates in the synthesis of photosensitizers but ignored in PDT applications. Here we found that halogen-bridged binuclear iridium complexes showed excellent performance in 1O2 generation. It was also confirmed that these complexes kill tumor cells by inducing apoptosis. Through molecular design and modification, we studied the effect of the bridging halogen atoms and intracellular localization on the performance of PDT. The results show that replacing the bridging halogen with heavier atoms and targeting the complex in mitochondria can effectively enhance the efficiency of PDT. Among them, the bromine bridged binuclear iridium complex located in mitochondria reported in this paper can achieve an IC50 value of 75 nM for MCF-7 cells. This work also provides inspiration for the exploration of complex-based photosensitizers.


Asunto(s)
Iridio , Fotoquimioterapia , Halógenos/farmacología , Iridio/farmacología , Mitocondrias , Fármacos Fotosensibilizantes
18.
Cardiol Res Pract ; 2022: 6558060, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35600331

RESUMEN

Cardiovascular disease, especially coronary artery disease and stroke, kills around one-third of the world's population, and myocardial infarction, a primary symptom of coronary heart disease, is a major worldwide health problem. Cardiovascular disease research has historically focused on promoting angiogenesis following myocardial damage. Myocardial vascular repair is crucial for improving myocardial infarction prognosis. Endothelial cells, the largest population of nonmyocytes within myocardial tissue, play an important role in angiogenesis. In recent years, different types of programmed cell death such as apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy have been described and found to be linked with cardiovascular diseases such as myocardial infarction, heart failure, and myocarditis. This will have important implications for reforming the treatment strategy of cardiovascular diseases. Different types of cell death of endothelial cells in myocardial infarction have been proposed, the roles and mechanisms of endothelial cell death in myocardial infarction are summarized in this review, and endothelial cell death inhibition as a therapeutic technique for treating myocardial infarction might be advantageous to human health.

19.
Biomed Opt Express ; 13(4): 1995-2005, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35519254

RESUMEN

Using in vivo multiphoton fluorescent dosimetry, we demonstrate that the clearance dynamics of Indocyanine Green (ICG) in the blood can quickly reveal liver function reserve. In normal rats, the ICG retention rate was below 10% at the 15-minute post-administration; While in the rat with severe hepatocellular carcinoma (HCC), the 15-minute retention rate is over 40% due to poor liver metabolism. With a 785 nm CW laser, the fluorescence dosimeter can evaluate the liver function reserve at a 1/10 clinical dosage of ICG without any blood sampling. In the future, this low-dosage ICG 15-minute retention dosimetry can be applied for the preoperative assessment of hepatectomy or timely perioperative examination.

20.
Nanomaterials (Basel) ; 12(9)2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35564177

RESUMEN

Here, we confined fluorescent probes to solid nanochannels to construct nanosensors, which not only significantly improved the reusability of the molecular probes, but also achieved ion current and fluorescence dual gating for more reliable detection. The combination of optical and electrical modalities can provide comprehensive spatiotemporal information that can be used to elucidate the sensing mechanism within the nanochannel. As a proof-of-concept experiment, fluorescein isothiocyanate (FITC)−hydrazine (N2H4) was selected to modify nanochannels for the effective detection of Hg2+. Based on spirolactam opening tactics, the system synergistically alters the surface charge and fluorescence intensity in response to Hg2+, establishing a dual open state of current and fluorescence. The newly prepared nanosensor exhibited a fast response (<1 min), high sensitivity, and selectivity towards Hg2+. Importantly, the nanodevice could be recovered by simple N2H4 treatment. Such sensing behavior could be used to implement optoelectronic dual-output XOR logical gates under the management of Hg2+ and N2H4. This strategy is anticipated to find broad applications in other nanochannel-based systems for various sensing applications used for monitoring of pollutants, food additives, and biomolecules.

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