- |||||||||| Review, Journal: The noncanonical NF?B pathway: Regulatory mechanisms in health and disease. (Pubmed Central) - Nov 14, 2024
It turns out that dysregulation of RelA and cRel, not RelB, is often implicated in mediating the resulting pathology. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Cancer > Molecular and Cellular Physiology Immune System Diseases > Stem Cells and Development.
- |||||||||| Journal: SOCS6, an inhibitory factor in Japanese eel inhibits the type I IFN pathway and the MyD88-mediated NF-kB pathway. (Pubmed Central) - Nov 13, 2024
Co-transfection of AjSOCS6 with AjMyD88 into HEK293 cells significantly reduced NF-?B luciferase activities compared to AjMyD88 single-transfection groups, in a natural state and under LPS stimulation. These findings suggest that AjSOCS6 negatively regulates MyD88-dependent NF-?B and type I IFN signaling pathways, underscoring its role in the immune defense of fish against viral and bacterial infections.
- |||||||||| Journal: A scallop I?B protein involved in innate immunity acts as a key regulator of NF-?B. (Pubmed Central) - Nov 13, 2024
These findings suggest that CfI?B1 plays a crucial role in regulating NF-?B activity, which is integral to the innate immunity of C. farreri. This research enhances our understanding of the innate immune system in invertebrates and provides a theoretical basis for developing disease-resistant scallops at the molecular level.
- |||||||||| Rituxan (rituximab) / Roche
Genetic Subclones Reveal Phenotypic Heterogeneity in Diffuse Large B-Cell Lymphoma (Marriott Grand Ballroom 5-6 (Marriott Marquis San Diego Marina)) - Nov 6, 2024 - Abstract #ASH2024ASH_1953;
In a validation cohort (n=574), the GC B cell theme was associated with a favorable response to R-CHOP chemotherapy (p<0.02), as expected, while the cell growth theme (but not the cell cycle theme) was associated with adverse survival (p<0.02)...In particular, our analysis suggests a functional role for the highly recurrent REL amplification in GCB DLBCL, which may be selected for its ability to block terminal memory B cell differentiation. Our paired scRNA and scATAC sequencing represents a significant resource for the lymphoma research community that illuminates the pathobiology of these malignancies.
- |||||||||| Journal: Shifts in embryonic oxygen levels cue heterochrony in limb initiation. (Pubmed Central) - Nov 1, 2024
This heterochronic shift is not due to changes in cis-regulatory sequences controlling T-box gene expression, but unexpectedly, is dependent upon differential oxygen levels to which avian and mammalian embryos are exposed prior to limb initiation, mediated, at least partially, by an NFKB transcription factor, cRel. Together, these results provide mechanistic understanding of an important example of developmental heterochrony and exemplify how the maternal environment regulates timing during embryonic development.
- |||||||||| Biomarker, Journal: Cumulative Health Risk from Exposure Load (CHREL): Looking at multi-chemical exposures through the lens of biomonitoring guidance values. (Pubmed Central) - Oct 31, 2024
The most important contributors to exposures above HB2GVs were inorganic arsenic, mercury, acrylamide, xylenes, benzene and triclosan. Keeping certain assumptions, uncertainties and limitations in mind, the CHREL indicator can be used to obtain a picture of potential cumulative health risks from combined chemical exposures in a population, and as a comparative measure between subpopulations, including vulnerable subgroups.
- |||||||||| Journal, IO biomarker: Glut3 promotes cellular O-GlcNAcylation as a distinctive tumor-supportive feature in Treg cells. (Pubmed Central) - Oct 29, 2024
Furthermore, by employing mouse tumor models and human clinical data, we identified the NF-?B subunit c-Rel as one such factor that, through Glut3-dependent O-GlcNAcylation, functionally orchestrates gene expression in Tregs at tumor sites. Together, these results not only identify immunometabolic alterations and molecular events contributing to fundamental aspects of Treg biology, specifically at tumor sites but also reveal tumor-specific cellular properties that can aid in the development of Treg-targeted cancer immunotherapies.
- |||||||||| Journal: Examining NF-?B genomic interactions by ChIP-seq and CUT&Tag. (Pubmed Central) - Aug 26, 2024
We also found considerable consistency between ChIP-seq and CUT&Tag results, but with a substantial fraction of genomic interactions detected with only one of the two techniques. Together, the results demonstrate the dramatic impact of experimental conditions on the results obtained in a genome-wide analysis of transcription factor binding, highlighting the need for further scrutiny of the functional significance of these condition-dependent differences.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg.
Journal, Metastases: Nanoparticle Polymeric Micellar Paclitaxel Versus Paclitaxel for Patients with Advanced Gastric Cancer. (Pubmed Central) - Aug 26, 2024
Together, the results demonstrate the dramatic impact of experimental conditions on the results obtained in a genome-wide analysis of transcription factor binding, highlighting the need for further scrutiny of the functional significance of these condition-dependent differences. NPMP combined chemotherapy offers a new, active, and safe treatment for patients with AGC.
- |||||||||| paclitaxel / Generic mfg.
Journal: PTX-RPPR, a conjugate of paclitaxel and NRP-1 peptide inhibitor to prevent tumor growth and metastasis. (Pubmed Central) - Aug 24, 2024
Characterized by a particle size of 200?nm and a zeta potential of +30?mV, the nano-formulation of PTX-RPPR demonstrated remarkable stability over seven days. This study introduced PTX-RPPR as a promising peptide-drug conjugate that addresses the solubility and hypersensitivity issues associated with paclitaxel, offering a safer therapeutic strategy for cancer treatment.
- |||||||||| Cortical spreading depolarization induces distinct transcriptomic responses in neurons, astrocytes, and microglia, shifting from pro to anti-inflammatory signaling within 24 hours. A potential mechanism contributing to headache termination (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_1489;
Consistent with the transcriptional data, no p65 nuclear translocation and inflammatory morphological phenotype were observed in microglia, suggesting that microglia may contribute to synaptic repair by surveilling injured dendrites with their processes, while inflammatory signaling in astrocytes can potentially stimulate/modulate the meningeal nociceptor activity through astrocyte endfeet abutting subarachnoid and perivascular spaces. In conclusion, following a single CSD, distinct transcriptomic responses occur in neurons, astrocytes, and microglia, suggesting tightly regulated inflammatory signaling, which is largely terminated within 24 hours, thus potentially contributing to headache resolution.
- |||||||||| Journal, IO biomarker: Synergy and antagonism in the integration of BCR and CD40 signals that control B-cell proliferation. (Pubmed Central) - Aug 12, 2024
Our quantitative findings highlight a complex non-monotonic integration of BCR and CD40 signals that is controlled by a balance between NF?B and cell-death pathways, and suggest a mechanism for regulating the stringency of B-cell selection during an antibody response. CD40 and BCR signaling in B-cells synergize to potentiate NF?B cRel activationBCR-apoptotic signaling may enhance or antagonize CD40-driven proliferationBCR-induced apoptosis may be rescued by CD40 within a temporal windowA mathematical model reveals regulators of the dose-dependent selection stringency.
- |||||||||| Journal, Immunogenic cell death, IO biomarker: Halting Multiple Myeloma with MALT1 Inhibition: Suppressing BCMA-Induced NF-?B and Inducing Immunogenic Cell Death. (Pubmed Central) - Jul 29, 2024
It was noteworthy that Mi-2 induces properties associated with immunogenic cell death (ICD), as evidenced by increased calreticulin (CRT), ATP release, and high-mobility group protein B1 (HMGB1) upregulation, consequently triggering ICD-associated immune activation and enhancing CD8+ T - cell cytotoxicity in vitro. In conclusion, our research highlights MALT1 as a promising druggable target for therapeutic interventions in MM, providing insights into its molecular mechanisms in MM progression.
- |||||||||| Journal, IO biomarker: The involvement of CgRHIM-containing protein in regulating haemocyte apoptosis after high temperature stress in Pacific oyster Crassostrea gigas. (Pubmed Central) - Jul 22, 2024
Moreover, the protein abundance of CgRHIM-containing protein increased significantly, and the ubiquitination level of CgRHIM-containing protein in haemocytes showed an increasing trend at first and then decreased. After the expression of CgRHIM-containing protein was knocked down by siRNA, the mRNA expression levels of CgRel and CgBcl-2 decreased significantly at 6 h after high temperature stress, and those of CgFADD-like, Cgcaspase-8 and Cgcaspase-3, as well as the apoptosis rate of haemocytes also decreased significantly at 24 h. These results indicated that CgRHIM-containing protein might regulate haemocyte apoptosis in oysters upon high temperature stress via mediating the expression of Rel, Bcl-2 and caspase-8/3.
- |||||||||| Journal: A novel surface marker CD49d promotes TNF expression in oyster agranulocytes by mediating the MAPK pathway. (Pubmed Central) - Jul 21, 2024
After the expression of CgRHIM-containing protein was knocked down by siRNA, the mRNA expression levels of CgRel and CgBcl-2 decreased significantly at 6 h after high temperature stress, and those of CgFADD-like, Cgcaspase-8 and Cgcaspase-3, as well as the apoptosis rate of haemocytes also decreased significantly at 24 h. These results indicated that CgRHIM-containing protein might regulate haemocyte apoptosis in oysters upon high temperature stress via mediating the expression of Rel, Bcl-2 and caspase-8/3. Furthermore, CgCD49d was found to be mainly expressed in the agranulocyte subpopulation, and Alexa Fluor 488-conjugated CgCD49d antibody labeled agranulocytes with a circle of green fluorescence signals on CgCD49d+ agranulocyte surface under Confocal microscopy, which accounted for 24.9
- |||||||||| MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
Mechanism of tau-mediated microglial NF-?B inhibitor I?B? degradation in Alzheimer (Exhibit (Pennsylvania Convention Center); In-Person) - Jun 19, 2024 - Abstract #AAIC2024AAIC_4502;
Microglial endocytosed AD-TO damages endomembrane and activate NF-kB by constitutively degrading IkB?, which localizes in autophagosomes, and concurrent inhibition of calpains and autophagy leading to secretion of IkB? into the extracellular space.
- |||||||||| Journal: Transient interactions modulate the affinity of NF-?B transcription factors for DNA. (Pubmed Central) - May 28, 2024
Binding and simulation studies with mutants supported these observations of transient interactions dictating specificity. In combination with published reports, this work provides insights into the nuanced mechanisms governing the discriminatory binding of NF-?B family TFs to ?B DNA elements and sheds light on cancer pathogenesis of cRel, a close homolog of RelA.
- |||||||||| Journal: Neuromorphic computing spiking neural network edge detection model for content based image retrieval. (Pubmed Central) - May 6, 2024
Importantly, our findings underscore the enhanced performance of CBIR methodologies integrating the proposed SNN-based edge detection approach, with an average increase in mean precision values exceeding 3%. This study conclusively demonstrated the utility of our proposed methodology in optimizing feature extraction, thereby establishing its pivotal role in advancing edge centric CBIR approaches.
- |||||||||| Exploring CK2 transcriptional regulation and signaling pathways in cancer. () - Apr 24, 2024 - Abstract #ASCO2024ASCO_4782;
Clinical Trial Registry-India (CTRI), CTRI/2010/091/001344 Registered on: 18 October 2010 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjEzNQ==&Enc=&userName=CTRI/2010/091/001344), CTRI/2015/07/006062 Registered on: 31 July 2015 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE2Mjc=&Enc=&userName=CTRI/2015/07/006062). Overall this study demonstrates significant correlations between CK2 gene expression and previously proposed transcriptional regulation mechanisms as well as known CK2 signaling pathways in cancer.
- |||||||||| Journal: Co-imaging of RelA and c-Rel reveals features of NF-?B signaling for ligand discrimination. (Pubmed Central) - Apr 1, 2024
Ligand discrimination is achieved through selective non-redundancy of RelA and c-Rel signaling dynamics, as well as their temporal coordination. These results suggest a potential role of c-Rel in fine-tuning immune responses and highlight the need for approaches that will elucidate the mechanisms regulating NF-?B subunit specificity.
- |||||||||| Zymfentra (infliximab-dyyb subcutaneous) / Celltrion
Interim Analysis of Subcutaneous Infliximab Cohort Study in Korea (Room A) - Mar 30, 2024 - Abstract #IMKASID2024IMKASID_83;
In conclusion, IFX -SC proves to be an effective and safe therapeutic option for patients with moderate -to-severe UC or CD in real -world settings, offering good drug survival and a tolerable saf ety profile. It also supports the possibility of switching from IFX -IV to IFX -SC, which enables individualized treatment approaches and improves compliance.
- |||||||||| O-GlcNAcylated NF-?B c-Rel is a transcriptional regulator of Acute Myeloid Leukemia (Exhibit Hall F1; Poster Board Number: B895) - Mar 29, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_1404;
We show that OGC350 treatment decreases viability of AML cells and suppresses expression of anti-apoptotic genes. Thus far, our data indicates that specific targeting of O-GlcNAcylated c-Rel has therapeutic promise for AML treatment by preventing activation of aberrant c-Rel activity while preserving normal functions of non-O-GlcNAcylated c-Rel.
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