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1.
J Ultrasound Med ; 2024 Sep 06.
Article de Anglais | MEDLINE | ID: mdl-39240020

RÉSUMÉ

OBJECTIVE: The aim of this study was to systematically investigate the ultrasonographic features of nodular hidradenoma (NH). METHODS: A retrospective analysis was used to systematically summarize the ultrasonographic data of 27 patients diagnosed with NH by surgical pathology, including 13 eccrine nodular hidradenomas (ENH) and 14 apocrine nodular hidradenomas (ANH). RESULTS: All instances of NH presented as solitary, well-defined lesions that infiltrated the dermis and subcutaneous fat layer, characterized by a heterogeneous hypoechoic internal solid component on ultrasound imaging. Color Doppler ultrasound revealed blood flow signals of Grade 2 or higher within 74% (20/27) of the lesions. Solid + cystic (cystic >50%) NH (14/27, 51.4%) were typically large and predominantly had an oval shape (11/14, 78.5%). Their distinctive sonographic features included the presence of inner septa within the cystic area (8/14, 57.1%), "snow falling" sign (7/14, 50%), or "fluid-fluid level" sign (7/14, 50%). Solid + cystic (cystic ≤50%) NH exhibited a lobulated morphology in all instances (5/5, 100%). No inner septa, "snow falling" sign or "fluid-fluid level" sign was observed within the cystic regions. The solid NH (8/27, 29.7%) morphology predominantly featured lobulation (6 out of 8, 75%). Ultrasound analysis revealed distinct differences between ENH and ANH. ENH were more lobulated, while ANH were predominantly oval. ANH were mainly solid + cystic (cystic >50%), whereas ENH were mostly solid. Inner septa, "snow falling" sign, and "fluid-fluid level" sign frequencies were similar in both groups, correlating more with cystic-solid composition than pathological subtype. CONCLUSIONS: Ultrasonographic features of lobulated morphology and the presence of inner septa, "snow falling" sign or "fluid-fluid level" sign in the cystic region provide strong support for the diagnosis of NH.

2.
World J Gastrointest Surg ; 16(8): 2511-2520, 2024 Aug 27.
Article de Anglais | MEDLINE | ID: mdl-39220074

RÉSUMÉ

BACKGROUND: Vascular and nerve infiltration are important indicators for the progression and prognosis of gastric cancer (GC), but traditional imaging methods have some limitations in preoperative evaluation. In recent years, energy spectrum computed tomography (CT) multiparameter imaging technology has been gradually applied in clinical practice because of its advantages in tissue contrast and lesion detail display. AIM: To explore and analyze the value of multiparameter energy spectrum CT imaging in the preoperative assessment of vascular invasion (LVI) and nerve invasion (PNI) in GC patients. METHODS: Data from 62 patients with GC confirmed by pathology and accompanied by energy spectrum CT scanning at our hospital between September 2022 and September 2023, including 46 males and 16 females aged 36-71 (57.5 ± 9.1) years, were retrospectively collected. The patients were divided into a positive group (42 patients) and a negative group (20 patients) according to the presence of LVI/PNI. The CT values (CT40 keV, CT70 keV), iodine concentration (IC), and normalized IC (NIC) of lesions in the upper energy spectrum CT images of the arterial phase, venous phase, and delayed phase 40 and 70 keV were measured, and the slopes of the energy spectrum curves [K (40-70)] from 40 to 70 keV were calculated. Arterial phase combined parameter, venous phase combined parameters (VP-ALLs), and delayed phase association parameters were calculated for patients with late-stage disease. The differences in the energy spectrum parameters between the positive and negative groups were compared, receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC), sensitivity, specificity, and optimal threshold were calculated to measure the diagnostic efficiency of each parameter. RESULTS: In the delayed phase, the CT40 keV, CT70 keV, K (40-70), IC, NIC, and CT70 keV and the NIC in the upper arterial and venous phases of energy spectrum CT were greater in the LVI/PNI-positive group than in the LVI-negative group. The representative parameters for the arterial phase NIC were 0.14 ± 0.04 in the positive group and 0.12 ± 0.04 in the negative group. The venous phase NIC was 0.5 (0.5, 0.6) in the positive group and 0.4 (0.4, 0.5) in the negative group. Last, for the delayed phase NIC, it was 0.6 ± 0.1 in the positive group and 0.5 ± 0.1 in the negative group (all P values are less than 0.05). ROC curve analysis demonstrated that the diagnostic efficacy of each parameter during the venous stage was superior to that during the arterial and delayed stages. Furthermore, the diagnostic efficacy of the combined parameter throughout all three stages was superior to that of any single parameter. The AUC, sensitivity, and specificity of the optimal parameter, VP-ALL, were 0.931 (95% confidence interval: 0.872-0.990), 80.95%, and 95.00%, respectively. CONCLUSION: When assessing the condition of LVI and PNI (perineural invasion) in patients with GC prior to surgery, the ability to diagnose these conditions using venous stage parameters was superior to that using arterial stage and delayed stage parameters. Furthermore, the diagnostic accuracy of using a combination of parameters was better than that of using individual parameters alone.

3.
Chem Soc Rev ; 2024 Aug 12.
Article de Anglais | MEDLINE | ID: mdl-39129564

RÉSUMÉ

Apoptosis, as type I cell death, is an active death process strictly controlled by multiple genes, and plays a significant role in regulating various activities. Mounting research indicates that the unique modality of cell apoptosis is directly or indirectly related to different diseases including cancer, autoimmune diseases, viral diseases, neurodegenerative diseases, etc. However, the underlying mechanisms of cell apoptosis are complicated and not fully clarified yet, possibly due to the lack of effective chemical tools for the nondestructive and real-time visualization of apoptosis in complex biological systems. In the past 15 years, various small-molecule fluorescent probes (SMFPs) for imaging apoptosis in vitro and in vivo have attracted broad interest in related disease diagnostics and therapeutics. In this review, we aim to highlight the recent developments of SMFPs based on enzyme activity, plasma membranes, reactive oxygen species, reactive sulfur species, microenvironments and others during cell apoptosis. In particular, we generalize the mechanisms commonly used to design SMFPs for studying apoptosis. In addition, we discuss the limitations of reported probes, and emphasize the potential challenges and prospects in the future. We believe that this review will provide a comprehensive summary and challenging direction for the development of SMFPs in apoptosis related fields.

4.
Biosens Bioelectron ; 264: 116656, 2024 Nov 15.
Article de Anglais | MEDLINE | ID: mdl-39133993

RÉSUMÉ

Human space activities have been continuously increasing. Astronauts experiencing spaceflight are faced with health problems caused by special space environments such as microgravity, and the investigation of cell injury is fundamental. The development of a platform capable of cell culture and injury detection is the prerequisite for the investigation. Constructing a platform suitable for special conditions in space life science research is the key issue. The ground-based investigation is an indispensable part of the research. Accordingly, a simulated microgravity (SMG)-oriented integrated chip platform capable of 3D cell culture and in situ visual detection of superoxide anion radical (O2•-) is developed. SMG can cause oxidative stress in human cells, and O2•- is one of the signaling molecules. Thus, a O2•--responsive aggregation-induced emission (AIE) probe is designed, which shows high selectivity and sensitivity to O2•-. Moreover, the probe exhibits abilities of long-term and wash-free staining to cells due to the AIE behavior, which is precious for space cell imaging. Meanwhile, a chip with a high-aspect-ratio chamber for adequate medium storage for the lack of the perfusion system during the SMG experiment and a cell culture chamber which can integrate the extracellular matrix (ECM) hydrogel for the bioinspired 3D cell culture is fabricated. In addition, a porous membrane is introduced between the chambers to prevent the hydrogel from separating during the SMG experiment. The afforded AIE probe-ECM hydrogel-integrated chip can achieve 3D culturing of U87-MG cells and in situ fluorescent detection of endogenous O2•- in the cells after long-term staining under SMG. The chip provides a powerful and potential platform for ground-based investigation in space life science and biomedical research.


Sujet(s)
Techniques de biocapteur , Hydrogels , Superoxydes , Humains , Superoxydes/analyse , Techniques de biocapteur/instrumentation , Techniques de biocapteur/méthodes , Hydrogels/composition chimique , Matrice extracellulaire/composition chimique , Techniques de culture cellulaire/instrumentation , Simulation d'apesanteur , Conception d'appareillage , Colorants fluorescents/composition chimique , Laboratoires sur puces , Impesanteur , Stress oxydatif
5.
Environ Pollut ; 361: 124848, 2024 Aug 29.
Article de Anglais | MEDLINE | ID: mdl-39214446

RÉSUMÉ

Profenofos (PFF) is a commonly used organophosphorus insecticide that requires strict monitoring due to its potential environmental, ecological, and human health risks originating from residues in soil and water systems, as well as accumulation in crops. In this study, a novel monoclonal antibody (mAb) specific to PFF was prepared for the first time and the recognition mechanism was investigated through molecular simulation. Subsequently, a mAb-based colloidal gold immunochromatographic assay (GICA) was developed for the rapid screening of PFF in fruit and vegetable samples. The mAb exhibited an IC50 value of 12.9 ng/mL, and limit of detection (LOD) of 4.6 ng/mL, respectively in indirect competitive immunosorbent enzyme-linked immunosorbent assay (ic-ELISA). After optimization, the developed GICA exhibited a visual limit of detection (vLOD) of 20 ng/mL and a quantitative of detection (qLOD) of 5.2 ng/mL, with a linear range from 10.0 to 83.8 ng/mL. Good correlation was observed between the results of GICA and standard Gas Chromatography-Tandem Mass Spectrometry (GC-MS/MS) in matrix and recovery test. The developed GICA can be used for rapid sample detection within 15 min, which is an excellent tool for screening PFF in foods and environmental samples.

6.
J Cell Mol Med ; 28(16): e70005, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39159135

RÉSUMÉ

The E-twenty-six variant 1 (ETV1)-dependent transcriptome plays an important role in atrial electrical and structural remodelling and the occurrence of atrial fibrillation (AF), but the underlying mechanism of ETV1 in AF is unclear. In this study, cardiomyocyte-specific ETV1 knockout (ETV1f/fMyHCCre/+, ETV1-CKO) mice were constructed to observe the susceptibility to AF and the underlying mechanism in AF associated with ETV1-CKO mice. AF susceptibility was examined by intraesophageal burst pacing, induction of AF was increased obviously in ETV1-CKO mice than WT mice. Electrophysiology experiments indicated shortened APD50 and APD90, increased incidence of DADs, decreased density of ICa,L in ETV1-CKO mice. There was no difference in VINACT,1/2 and VACT,1/2, but a significantly longer duration of the recovery time after inactivation in the ETV1-CKO mice. The recording of intracellular Ca2+ showed that there was significantly increased in the frequency of calcium spark, Ca2+ transient amplitude, and proportion of SCaEs in ETV1-CKO mice. Reduction of Cav1.2 rather than NCX1 and SERCA2a, increase RyR2, p-RyR2 and CaMKII was reflected in ETV1-CKO group. This study demonstrates that the increase in calcium spark and SCaEs corresponding to Ca2+ transient amplitude may trigger DAD in membrane potential in ETV1-CKO mice, thereby increasing the risk of AF.


Sujet(s)
Fibrillation auriculaire , Calcium , Atrium du coeur , Souris knockout , Myocytes cardiaques , Facteurs de transcription , Animaux , Myocytes cardiaques/métabolisme , Souris , Fibrillation auriculaire/métabolisme , Fibrillation auriculaire/génétique , Calcium/métabolisme , Atrium du coeur/métabolisme , Facteurs de transcription/métabolisme , Facteurs de transcription/génétique , Protéines de liaison à l'ADN/métabolisme , Protéines de liaison à l'ADN/génétique , Signalisation calcique , Potentiels d'action , Potentiels de membrane , Mâle
7.
Sci Adv ; 10(33): eadn6272, 2024 Aug 16.
Article de Anglais | MEDLINE | ID: mdl-39150998

RÉSUMÉ

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.


Sujet(s)
Anxiété , Neurones GABAergiques , Aire hypothalamique latérale , Prurit , Animaux , Souris , Neurones GABAergiques/métabolisme , Maladie chronique , Modèles animaux de maladie humaine , Noyaux médians du thalamus/métabolisme , Mâle , Comportement animal , Voies nerveuses , Plasticité neuronale , Noyaux du septum
8.
Angew Chem Int Ed Engl ; : e202412651, 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39030810

RÉSUMÉ

Photonic heterostructures with codable properties have shown great values as versatile information carriers at the micro and nanoscale. These heterostructures are typically prepared by a step-by-step growth or post-functionalization method to achieve varied emission colors among different building blocks. In order to realize high-throughput and multivariate information loading, we report here a strategy to integrate polarization signals into photonic heterojunctions. A U-shaped di-Pt(II) complex is assembled into highly-polarized yellow-phosphorescent crystalline microrods (Y-rod) by strong intermolecular Pt···Pt interaction. Upon end-initiated desorption of the incorporated CH2Cl2 solvents, Y-rod is transformed in a domino fashion into tri-block polarized photonic heterojunctions (PPHs) with alternate red-yellow-red emissions or red-phosphorescent microrods (R-rod). The red emissions of these structures are also highly polarized; however, their polarization directions are just orthogonal to those of the yellow phosphorescence of Y-rod. With the aid of a patterned mask, R-rod is further programmed into multi-block PPHs with precisely-controlled block sizes by side-allowed adsorption of CH2Cl2 vapor. X-ray diffraction analysis and theoretical calculations suggest that the solvent-regulated modulation of intramolecular and intermolecular excited states is critical for the construction of these PPHs.

9.
Talanta ; 279: 126561, 2024 Nov 01.
Article de Anglais | MEDLINE | ID: mdl-39047628

RÉSUMÉ

Acute lung injury (ALI) is a serious pulmonary inflammatory disease resulting from excessive reactive oxygen species (ROS) which could cause the damage of the alveolar epithelial cells and capillary endothelial cells. Peroxynitrite, as one of short-lived reactive oxygen species, is closely related to the process of ALI. Thus, it is important to monitor the fluctuation of peroxynitrite in living system for understanding the process of ALI. Herein, the novel mitochondria-targeted fluorescent probe BHMT was designed to respond to peroxynitrite and pH with distinct fluorescence properties respectively. The absorption spectrum of the probe BHMT exhibited a notable red shift as the pH value declined from 8.8 to 2.6. Upon reaction with peroxynitrite, BHMT had a significant increase of fluorescence intensity (63-fold) with maintaining a detection limit of only 43.7 nM. Furthermore, BHMT could detect the levels of endogenous peroxynitrite and image the intracellular pH in ratiometric channels utilizing cell imaging. In addition, BHMT was successfully applied to revealing the relationship between the peroxynitrite and the extent of ALI. Thus, these results indicated the probe BHMT could be a potential tool for diagnosing the early stage of ALI and revealed the peroxynitrite was likely to be a crucial therapeutic target in ALI treatment.


Sujet(s)
Lésion pulmonaire aigüe , Colorants fluorescents , Mitochondries , Acide peroxynitreux , Acide peroxynitreux/métabolisme , Acide peroxynitreux/analyse , Lésion pulmonaire aigüe/imagerie diagnostique , Lésion pulmonaire aigüe/métabolisme , Colorants fluorescents/composition chimique , Mitochondries/métabolisme , Humains , Animaux , Concentration en ions d'hydrogène , Souris , Imagerie optique , Mâle
10.
Transl Pediatr ; 13(6): 987-993, 2024 Jun 30.
Article de Anglais | MEDLINE | ID: mdl-38984022

RÉSUMÉ

Background: Acral persistent papular mucinosis (APPM) is a rare idiopathic subtype of localized lichen myxedematosus. To date, there have been less than 41 APPM cases reported worldwide, however, almost all patients were older than 18 years of age. A 7-year-old child was first reported in this paper. Case Description: A 7-year-old boy was admitted to our hospital with a solitary skin-colored papule on the radial side of the middle segment of his right index finger. The patient wanted to know the exact diagnosis and remove it because the flexion movement of the middle segment had been affected. Thus, a surgery was performed. Histopathological examination of a biopsy specimen obtained from the papule on the radial side of the middle segment of his right index finger showed a focal and well-circumscribed deposit of mucin in the papillary and middermis. The deposit never extended deeply into the reticular dermis. Mucin spared a subepidermal area in the papillary dermis. Alcian blue stains can highlight the mucin. The papule was histologically diagnosed as an APPM and excised surgically. The wound gradually healed after the operation, and no obvious recurrence, scar or other discomfort was observed during follow-up so far. Conclusions: To the best of our knowledge, this is the rare case of a child APPM presenting as a solitary papule affecting the flexion movement of the middle segment. Since it is a rare disease, we report this case to contribute to future research on the diagnosis and pathogenesis of APPM.

11.
RSC Adv ; 14(31): 22229-22237, 2024 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-39010912

RÉSUMÉ

Bio-based materials with excellent acoustic absorption properties are in great demand in architecture, interior, and human settlement applications for efficient noise control. In this study, crayfish shells, a form of kitchen waste, are utilized as the primary material to produce ultralight and multifunctional chitin aerogels, which effectively eliminate noise. Different replacement solvents and freezing rates were employed to regulate the porous structures of chitin aerogels, and their resulting acoustic absorption performance was investigated. Results demonstrate that employing deionized water as the replacement solvent and utilizing a common-freeze mode (frozen via refrigerator at -26 °C) can produce chitin aerogels with larger porosity (96.26%) and apertures, as well as thicker pore walls. This results in superior broadband acoustic absorption performance (with a maximum absorption coefficient reaching 0.99) and higher Young's modulus (28 kPa). Conversely, chitin aerogels solvent-exchanged with tert-butyl alcohol or subjected to quick-freeze mode (frozen via liquid nitrogen) exhibit smaller porosity (92.32% and 94.84%) and apertures, thereby possessing stronger diffuse reflection of visible light (average reflectance of 94.30% and 88.18%), and enhanced low-frequency (500 to 1600 Hz) acoustic absorption properties. Additionally, the acoustic absorption mechanism of fabricated chitin aerogels was predicted using a simple three-parameter analysis Johnson-Champoux-Allard-Lafarge (JCAL) model. This study presents a novel approach to developing multifunctional biomass materials with excellent acoustic absorption properties, which could have a wide range of potential applications.

12.
J Org Chem ; 89(12): 8706-8720, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38825808

RÉSUMÉ

In this study, we systematically investigated the regioselective glycosylation of 2,4-OH mannoside and galactoside acceptors since regioselective protection of their 3- and 6-OHs is readily achieved. By altering the protecting groups at 1-, 3-, and 6-positions of such acceptors, we finally screened p-methoxyphenyl 3-OBn, 6-OTBDPS, α-mannoside, and ß-galactoside acceptors whose 2-OHs exhibited excellent selectivity for glycosylation with various glycosyl donors, leading to 1,2-linked products in 70-82% yields. By utilizing such acceptors, a series of 2,4-linked trisaccharide products (53-65% yields over two steps) have been highly efficiently synthesized without the need for complex protection/deprotection operations at the 2- and 4-positions of these acceptors.

13.
Chem Commun (Camb) ; 60(50): 6362-6374, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38836312

RÉSUMÉ

Multicomponent tandem reactions have become indispensable synthetic methods due to their economic advantages and efficient usage in natural products and drug synthesis. The emergence of metalated covalent organic frameworks (MCOFs) has opened up new opportunities for the advancement of multicomponent tandem reactions. In contrast to commonly used homogeneous transition metal catalysts, MCOFs possess regular porosity, high crystallinity, and rich metal chelation sites that facilitate the uniform distribution and anchoring of metals within their cavities. Thus, they show extremely high activity and have recently been widely employed as catalysts for multicomponent tandem reactions. It is timely to conduct a review of MCOFs in multicomponent tandem reactions, in order to offer guidance and assistance for the synthesis of MCOF catalysts and their application in multicomponent tandem reactions. This review provides a comprehensive overview of the design and synthesis of MCOFs, their application and progress in multicomponent tandem reactions, and the primary challenges encountered during their current development with the aim of contributing to the promotion of the field.

15.
Int J Gen Med ; 17: 2299-2309, 2024.
Article de Anglais | MEDLINE | ID: mdl-38799198

RÉSUMÉ

Objective: This study aimed to explore specific biochemical indicators and construct a risk prediction model for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Methods: This study included 234 T2D patients, of whom 166 had DKD, at the First Hospital of Jilin University from January 2021 to July 2022. Clinical characteristics, such as age, gender, and typical hematological parameters, were collected and used for modeling. Five machine learning algorithms [Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF)] were used to identify critical clinical and pathological features and to build a risk prediction model for DKD. Additionally, clinical data from 70 patients (nT2D = 20, nDKD = 50) were collected for external validation from the Third Hospital of Jilin University. Results: The RF algorithm demonstrated the best performance in predicting progression to DKD, identifying five major indicators: estimated glomerular filtration rate (eGFR), glycated albumin (GA), Uric acid, HbA1c, and Zinc (Zn). The prediction model showed sufficient predictive accuracy with area under the curve (AUC) values of 0.960 (95% CI: 0.936-0.984) and 0.9326 (95% CI: 0.8747-0.9885) in the internal validation set and external validation set, respectively. The diagnostic efficacy of the RF model (AUC = 0.960) was significantly higher than each of the five features screened with the highest feature importance in the RF model. Conclusion: The online DKD risk prediction model constructed using the RF algorithm was selected based on its strong performance in the internal validation.

16.
ACS Appl Mater Interfaces ; 16(21): 27566-27575, 2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38743438

RÉSUMÉ

We selectively improved the viewing angle characteristics and light extraction efficiency of blue thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs) by tailoring a nanofiber-shaped Si3N4 layer, which was used as an internal scattering layer. The diameter of the polymer nanofibers changed according to the mass ratio of polyacrylonitrile (PAN) and poly(methyl methacrylate) (PMMA) in the polymer solution for electrospinning. The Si3N4 nanofiber (SNF) structure was fabricated by etching an Si3N4 film using the PAN/PMMA nanofiber as a mask, making it easier to adjust parameters, such as the diameter, open ratio, and height, even though the SNF structure was randomly shaped. The SNF structures exhibited lower transmittance and higher haze with increasing diameter, showing little correlation with their height. However, all the structures demonstrated a total transmittance of over 80%. Finally, by applying the SNF structures to the blue TADF OLEDs, the external quantum efficiency was increased by 15.6%. In addition, the current and power efficiencies were enhanced by 23.0% and 25.6%, respectively. The internal light-extracting SNF structure also exhibited a synergistic effect with the external light-extracting structure. Furthermore, when the viewing angle changed from 0° to 60°, the peak wavelength and CIE coordinate shift decreased from 20 to 6 nm and from 0.0561 to 0.0243, respectively. These trends were explained by the application of Snell's law to the light path and were ultimately validated through finite-difference time-domain simulations.

17.
J Med Chem ; 67(10): 7921-7934, 2024 May 23.
Article de Anglais | MEDLINE | ID: mdl-38713486

RÉSUMÉ

CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.


Sujet(s)
Tumeurs du sein , Prolifération cellulaire , Protein-arginine N-methyltransferases , Humains , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Protein-arginine N-methyltransferases/antagonistes et inhibiteurs , Protein-arginine N-methyltransferases/métabolisme , Femelle , Animaux , Souris , Prolifération cellulaire/effets des médicaments et des substances chimiques , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/usage thérapeutique , Lignée cellulaire tumorale , Souris nude , Souris de lignée BALB C , Antienzymes/pharmacologie , Antienzymes/composition chimique , Antienzymes/usage thérapeutique
19.
Nucleic Acids Res ; 52(12): 6811-6829, 2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38676947

RÉSUMÉ

Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.


Sujet(s)
Tumeurs du sein , Assemblage et désassemblage de la chromatine , Régulation de l'expression des gènes tumoraux , Complexe Mi-2/NuRD , Protein-arginine N-methyltransferases , Complexe Mi-2/NuRD/métabolisme , Complexe Mi-2/NuRD/génétique , Protein-arginine N-methyltransferases/génétique , Protein-arginine N-methyltransferases/métabolisme , Tumeurs du sein/génétique , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Humains , Femelle , Animaux , Lignée cellulaire tumorale , Cycle cellulaire/génétique , Souris , Méthylation , Arginine/métabolisme , Carcinogenèse/génétique , Activation de la transcription
20.
Angew Chem Int Ed Engl ; 63(25): e202402882, 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38594208

RÉSUMÉ

Circularly polarized luminescence (CPL)-active molecular materials have drawn increasing attention due to their promising applications for next-generation display and optoelectronic technologies. Currently, it is challenging to obtain CPL materials with both large luminescence dissymmetry factor (glum) and high quantum yield (Φ). A pair of enantiomeric N N C-type Pt(II) complexes (L/D)-1 modified with chiral Leucine methyl ester are presented herein. Though the solutions of these complexes are CPL-inactive, the spin-coated thin films of (L/D)-1 exhibit giantly-amplified circularly polarized phosphorescences with |glum| of 0.53 at 560 nm and Φair of ~50 %, as well as appealing circular dichroism (CD) signals with the maximum absorption dissymmetry factor |gabs| of 0.37-0.43 at 480 nm. This superior CPL performance benefits from the hierarchical formation of crystalline fibrillar networks upon spin coating. Comparative studies of another pair of chiral Pt(II) complexes (L/D)-2 with a symmetric N C N coordination mode suggest that the asymmetric N N C coordination of (L/D)-1 are favorable for the efficient exciton delocalization to amplify the CPL performance. Optical applications of the thin films of (L/D)-1 in CPL-contrast imaging and inducing CP light generation from achiral emitters and common light-emitting diode lamps have been successfully realized.

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