CBP OR P300 OR CREBBP OR EP300

The senescence of alveolar epithelial cells (AECs) and fibroblasts plays a pivotal role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a condition lacking specific therapeutic interventions. Curculigoside (CCG), a prominent bioactive constituent of Curculigo , exhibits anti-osteoporotic and antioxidant activities. Our investigation aimed to elucidate the anti-senescence and anti-fibrotic effects of CCG in experimental pulmonary fibrosis and delineate its underlying molecular mechanisms. Our findings demonstrate that CCG attenuates bleomycin-induced pulmonary fibrosis and lung senescence in murine models, concomitantly ameliorating lung function impairment...

The long-term maintenance of leukaemia stem cells (LSCs) is responsible for the high degree of malignancy in MLL (mixed-lineage leukaemia) rearranged acute myeloid leukaemia (AML). The DNA damage response (DDR) and DOT1L/H3K79me pathways are required to maintain LSCs in MLLr-AML, but little is known about their interplay. This study revealed that the DDR enzyme ATM regulates the maintenance of LSCs in MLLr-AML with a sequential protein-posttranslational-modification manner via CBP-DOT1L. We identified the phosphorylation of CBP by ATM, which confers the stability of CBP by preventing its proteasomal degradation, and characterised the acetylation of DOT1L by CBP, which mediates the high level of H3K79me2 for the expression of leukaemia genes in MLLr-AML...

In the ongoing evolutionary arms race between predators and prey, adaptive innovations often trigger a reciprocal response. For instance, the emergence of α-neurotoxins in snake venom has driven prey species targeted by these snakes to evolve sophisticated defense mechanisms. This study zeroes in on the particular motifs within the orthosteric sites of post-synaptic nicotinic acetylcholine receptors (nAChR) that confer resistance to α-neurotoxins, often through structural alterations of nAChR. This research examined Australian agamid lizards, a primary prey group for Australian elapid snakes, which are subject to predatory selection pressures...

Despite the design and proposal of several new structural motifs as thermally activated delayed fluorescent (TADF) emitters for organic light-emitting device (OLED) applications, the nature of their interaction with the host matrix in the emissive layer of the device and their influence on observed photophysical outputs remain unclear. To address this issue, we present, for the first time, the use of up to four regioisomers bearing a donor-acceptor-donor electronic structure based on the desymmetrized naphthalene benzimidazole scaffold, equipped with various electron-donating units and possessing distinguished conformational lability...

Respiratory diseases significantly affect intensive pig farming, causing production losses and increased antimicrobial use. Accurate classification of lung lesions is crucial for effective diagnostics and disease management. The integration of non-destructive and rapid techniques would be beneficial to enhance overall efficiency in addressing these challenges. This study investigates the potential of near-infrared (NIR) spectroscopy in classifying pig lung tissues. The NIR spectra (908-1676 nm) of 101 lungs from weaned pigs were analyzed using a portable instrument and subjected to multivariate analysis...

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis-Specific Protein Y-encoded-Like 2 (TSPYL2) plays a fibrogenic role in diabetes-associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress in vitro and in vivo ...

BACKGROUND: Carotid body paraganglioma (CBP) is a rare, highly vascularized, and slow-growing neuroendocrine tumor. Surgical resection is the definitive treatment for CBP, however, it remains challenging due to the tumor's proximity to critical blood vessels and cervical cranial nerves. This study aimed to document the characteristics of CBP and examine the clinical outcomes of patients following surgical extirpation of CBP. METHODS: This is a single-center retrospective review analyzed patients who underwent CBP extirpation...

Chemical discovery efforts commonly target individual protein domains. Many proteins, including the EP300/CBP histone acetyltransferases (HATs), contain several targetable domains. EP300/CBP are critical gene-regulatory targets in cancer, with existing high potency inhibitors of either the catalytic HAT domain or protein-binding bromodomain (BRD). A domain-specific inhibitory approach to multidomain-containing proteins may identify exceptional-responding tumor types, thereby expanding a therapeutic index. Here, we discover that targeting EP300/CBP using the domain-specific inhibitors, A485 (HAT) or CCS1477 (BRD) have different effects in select tumor types...

Disruption of the thyroid hormone system by synthetic chemicals is gaining attention owing to its potential negative effects on organisms. In this study, the effects of the dio-inhibitor iopanoic acid (IOP) on the levels of thyroid hormone and related gene expression, swim bladder inflation, and swimming performance were investigated in Japanese medaka. Iopanoic acid exposure suppressed thyroid-stimulating hormone β (tshβ), tshβ-like, iodotyronin deiodinase 1 (dio1), and dio2 expression, and increased T4 and T3 levels...

OBJECTIVE: Verbal retrieval (VR) deficits often occur after traumatic brain injury (TBI), but the mechanisms remain unclear. We examined how event-related potentials (ERPs) during a Go-NoGo task were associated with VR deficits. METHODS: Sixty veterans with a history of TBI underwent a neuropsychological battery and a Go-NoGo task with concurrent EEG recording. We compared task performance and ERP measures (N2, P3) between those with and those without persistent injury-related VR deficits...

INTRODUCTION: Atopic dermatitis (AD) is an inflammatory skin condition that affects millions of pediatric and adult patients with well-studied impact on morbidity and quality of life. Management occurs in a stepwise fashion beginning with preventative measures before immunomodulators are introduced. However, challenges remain in treatment of moderate-to-severe atopic dermatitis that is refractory to first- and second-line treatments and there are only few topical anti-inflammatory options, especially for pediatric patients...

BACKGROUND: Concurrent follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)was reported in some studies, while the diagnosis of TdT (terminal deoxynucleotydil transferase) positive high grade B cell lymphoma (HGBL) with MYC and BCL2 rearrangements ("double hit") transformed from FL/DLBCL has been rarely reported. Herein, we described the clinical features and mutation profiles of a case diagnosed with TdT positive "double hit" HGBL following the treatment of FL/DLBCL. CASE PRESENTATION: This is a 43-year-old Chinese man who was diagnosed with low grade FL (account for 80%) combined with DLBCL (20%) at a stage of IVB...

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance...

BACKGROUND: Brain-computer interface (BCI) technology offers children with quadriplegic cerebral palsy unique opportunities for communication, environmental exploration, learning, and game play. Research in adults demonstrates a negative impact of fatigue on BCI enjoyment, while effects on BCI performance are variable. To date, there have been no pediatric studies of BCI fatigue. The purpose of this study was to assess the effects of two different BCI paradigms, motor imagery and visual P300, on the development of self-reported fatigue and an electroencephalography (EEG) biomarker of fatigue in typically developing children...

Transfer learning has become an important issue in the brain-computer interface (BCI) field, and studies on subject-to-subject transfer within the same dataset have been performed. However, few studies have been performed on dataset-to-dataset transfer, including paradigm-to-paradigm transfer. In this study, we propose a signal alignment for P300 event-related potential (ERP) signals that is intuitive, simple, computationally less expensive, and can be used for cross-dataset transfer learning.

Approach...

The development of targeted anti-cancer therapeutics offers the potential for increased efficacy of drugs and diagnostics. Utilizing modalities agnostic to tumor type, such as the hypoxic tumor microenvironment (TME), may assist in the development of universal tumor targeting agents. The hypoxia-inducible factor (HIF), in particular HIF1, plays a key role in tumor adaptation to hypoxia, and inhibiting its interaction with p300 has been shown to provide therapeutic potential. Using a multivalent assembled protein (MAP) approach based on the self-assembly of the cartilage oligomeric matrix protein coiled-coil (COMPcc) domain fused to the critical residues of the C-terminal transactivation domain (C-TAD) of the α subunit of HIF1 (HIF1α), we generate HIF1α-MAP (H-MAP)...

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a chronic breathing disorder characterized by recurrent upper airway obstruction during sleep. Although previous studies have shown a link between OSAHS and depressive mood, the neurobiological mechanisms underlying mood disorders in OSAHS patients remain poorly understood. This study aims to investigate the emotion processing mechanism in OSAHS patients with depressive mood using event-related potentials (ERPs). METHODS: Seventy-four OSAHS patients were divided into the depressive mood and non-depressive mood groups according to their Self-rating Depression Scale (SDS) scores...

BACKGROUND: The prevalence of depressive disorder is increasing due to a variety of factors, which brings a huge strain on individuals, families and society. This study aims to investigate whether there is Frontal Theta Asymmetry (FTA) in depressed patients, and whether FTAs are related to depression severity and cognitive function changes in depressed patients. METHODS: Participants who met the inclusion criteria were enrolled in this study. Socio-demographic data of each participant were recorded...

Developing an insoluble cross-linkable hole transport layer (HTL) plays an important role for solution-processed quantum dots light-emitting diodes (QLEDs) to fabricate a multilayer device with separated quantum dots layers and HTLs. In this work, a facile photothermal synergic cross-linking strategy is simultaneous annealing and UV irradiation to form the high-quality cross-linked film as the HTL without any photoinitiator, which efficiently reduces the cross-linking temperature to the low temperature of 130 °C and enhances the hole mobility of the 3-vinyl-9-{4-[4-(3-vinylcarbazol-9-yl)phenyl]phenyl}carbazole (CBP-V) thin films...

Cyanobacteria, red algae, and cryptophytes produce two classes of proteins for light-harvesting: water-soluble phycobiliproteins and membrane-intrinsic proteins that bind chlorophylls and carotenoids. In cyanobacteria, red algae, and glaucophytes, phycobilisomes (PBS) are complexes of brightly colored phycobiliproteins and linker (assembly) proteins. To date, six structural classes of phycobilisomes have been described: hemiellipsoidal, block-shaped, hemidiscoidal, bundle-shaped, paddle-shaped, and far-red-light bicylindrical...