Neuroblastoma

Spatial transcriptomics delineated the molecular variant expressions of hub gene JAK1 in malignant cells across cancers, while immunohistochemistry validated the differential protein levels of JAK1 in NB. Based on multi-omics analysis and ML algorithms, we successfully developed the SCRS to enable accurate diagnosis and prognostic stratification in NB, which shed light on molecular landscapes of senes CAF and clinical utilization of SCRS.

P1/2, N=38, Terminated, Hoffmann-La Roche | Completed --> Terminated; Study was terminated by the sponsor based on insufficient tolerability and efficacy to proceed beyond Part 1b.

The detail of these interactions provides insight into a process critical for the assembly of paraspeckles as well as the behaviour of SFPQ as a transcription factor, and general multipurpose auxiliary protein with functions essential to mammalian life. Our understanding of the coiled coil behaviour of SFPQ also enhances the explanatory power of mutations (often disease-associated) observed in the DBHS family, potentially allowing for the development of future medical options such as targeted gene therapy.

Conversely, the low-risk group demonstrated potential immunotherapy effectiveness and increased sensitivity to anti-tumor drugs. We established a prognostic model based on DRLs to predict the prognosis of NB patients, assess the immune cell infiltration, analyze TMB, evaluate the effectiveness of immunotherapy, and gauge sensitivity to anti-tumor drug treatments.

Finally, expression of the HuR-V225I mutant decreases the cell's response to apoptotic stimuli through the increased expression of mRNAs encoding anti-apoptotic factors, such as XIAP and BCL-2. Therefore, our data establishes that the absence of HuR cytoplasmic translocation and cleavage promotes cell viability, and that acquiring this mutation during tumorigenesis may thus reduce the efficacy of cancer therapy.

Activation of the TRPM3/CaMKKβ/AMPK pathway promoted collateral sprouting of sensory axons, positioning TRPM3 as a promising therapeutic target for peripheral neuropathy.

Caspase 3/7 activity was significantly reduced in both cells, while efficient cellular uptake was noted. The present study provided a solid basis as a proof of principle study for future applications of the potential therapeutic in vitro, promising to address the unmet medical needs of patients with neurological disorders.

These results suggest that pterostilbene may offer neuroprotective advantages for differentiated neuronal-like cells. However, further studies are required to confirm these effects in vivo by examining specific biomarkers in human populations consuming pterostilbene-containing foods.

In ONB, relative to SNUC and SNEC, the SSTR2 expression profile, combined with its immune profiles, indicates potential novel therapeutic strategies and combinations for this unmet clinical need. Conversely, the inflammatory microenvironment of SNUC may be targetable using immuno-oncologic therapies.

This review aims to capture the most recent studies that investigate metabolic rewiring in MYCN-amplified and MYCN-activated cells from the perspective of alterations to glycolysis, the TCA cycle, and oxidative phosphorylation, in addition to changes to amino acid, nucleotide, and lipid metabolism that can be relevant to therapy. A better understanding of the metabolic profile of MYCN-amplified disease will facilitate the identification of effective treatment options and improve the prognosis of high-risk neuroblastoma patients.

Conversely, the reduced levels of HuD leads to decreased Msi2 expression and increased APAF1 levels, which results in apoptosis in N2a cells. Overall, our research indicates that HuD and Msi2 possess an anti-apoptotic role in N2A cells.

We provide evidence that PPAR ligands in combination with CIK cell immunotherapy could be a valuable option for malignant CNS tumors.

Our findings indicate that SL showed protective effects against rotenone-induced OS, mitochondrial complex-I in neuronal cell damage, which suggests that SL might potentially serve as an anti-PD remedial candidate for PD treatment.

Activity of the lncRNA NEAT1 can be triggered via CARM1, which synchronously promotes NB development via the miR-873-5p/MYCN and miR-873-5p/GalNAcT-I axes. These findings shed light on the novel molecular mechanisms underlying NB progression.

18F-OC could be used in the evaluation of NB, and the modified Curie scoring system could be used to semi-quantify the disease extent of NB in 18F-OC PET/CT.

Although surgical intervention serves as the primary treatment for early-stage disease, advanced-stage cases necessitate a variety of oncologic therapeutic approaches, including 131I-MIBG and peptide receptor radionuclide therapy. Herein we report incidental pineal gland activity, represented in 68Ga-DOTATATE PET/CT (SSTR-PET) in 3 pediatric patients diagnosed with stage 4 neuroblastoma, related to the physiological distribution of radiopharmaceuticals.

Our research shows that the dysregulation of miR-9, miR-222, and MMP14 could be key indicators in the pathogenesis of neuroblastoma. We also found that up-regulation of miR-9 was associated with decreased disease severity, whereas up-regulation of miR-222 and MMP14 was linked to increased disease severity.

The insilico docking analysis denotes that betanin had a significant docking score with the target molecules. Thus, from the invitro and insilico studies, betanin strongly inhibit the toxic effects of Aβand protect the cells from degeneration.

By performing cP-RNA-seq, which selectively captures cP-containing RNAs, we identified Ang-generated tRNA halves and the specific cleavage positions within tRNA anticodon-loops responsible for their generation. Our results provide insights into the anticodon-loop cleavage and the selective production of a specific subset of tRNA halves by Ang.

We further found that sarkosyl-insoluble phosphorylated tau was increased in cultured hippocampal neurons due to glutamate-induced hyperactivity. Our data suggest that hyperphosphorylated tau synthesized in response to NMDA receptor stimulation contributes to regulation of neuronal activity by binding calcium ions, but that this calcium binding may cause tau to adopt an aggregated form.

P1, N=44, Active, not recruiting, University Hospital Southampton NHS Foundation Trust | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2024 --> May 2025

It significantly decreased ROS levels (p < .001), preserved mitochondrial membrane potential, and moderated upregulation of apoptotic (CytC, Casp3, and Bax) and autophagic genes (Beclin-1, and LC-3) and down-regulation of Bcl-2 as an anti-apoptotic gene. Similar naringenin-mediated patterns were observed for cytochrome C and caspase 3 proteins. Naringenin administration can be considered for treating the neurotoxic effects of methamphetamine.

While HUC-MSC-exo could significantly alleviate the cytotoxicity, apoptosis and inflammatory effects induced by lead on SH-SY5Y cells via partially restoring miR-26a-5p/PTEN pathway. Herein, we conclude that HUC-MSC-exo can alleviate lead-induced toxic effects on SH-SY5Y cells partially through miR-26a-5p/PTEN pathway.

These findings collectively indicate that surface modification of EVs with dopamine presents a potent strategy for targeting dopaminergic neurons in the brain. The remarkable therapeutic potential of Dopa-EVs, demonstrated in PD models, positions them as a highly promising candidate for PD treatment, offering a significant advance over current therapeutic modalities.

These findings provide crucial insights into the nervous system's effectiveness and potential cardiovascular or nervous system adverse reactions from core compound combinations. This study provides insights into the TCM interpretation, drug compatibility or combined medication for further clinical application or potential drug pairs with a cost-effective method of integrated network pharmacology and deep learning.

The rs3803662 is located in CASC16:miRNA binding sites, which has positive effects on hsa-miR-4475 and hsa-miR-7845-5p and negative effects on hsa-miR-4524a-3p and hsa-miR-4524b-3p. These haplotypic structures and lncRNA:miRNA:SNP interactions on CASC family lncRNAs reveal novel genetic associations between CASC genes and various cancers.

Nrf2 deficiency negated the neuroprotective effects of filbertone in MPTP-treated mice. Consequently, our finding suggests that filbertone is a novel therapeutic agent for neurodegenerative diseases, enhancing neuronal resilience through the Nrf2 signaling pathway and upregulation of neurotrophic factors.

We investigate the interplay between TERT activation, overexpression and copy-number dosage and reveal loss of imprinting at the RTL1 gene associated with poor clinical outcome. These results highlight the importance of gene dosage in key oncogenic mechanisms in neuroblastoma.

Notably, HIF-1α regulated the expression of cell cycle inhibitory proteins (p16, p21, p53) and senescence-associated secretory phenotype factors (IL-8, IL-6, CCL2), along with the expression of senescence-associated β-galactosidase, thereby exacerbating T-2 toxin-induced cellular senescence. These findings underscore the vital role of HIF-1α in T-2 toxin-induced senescence in SH-SY5Y cells.

Meanwhile, the PINK1/Parkin-mediated mitophagy was activated after ASIV administration, which ameliorated ZnONPs-induced SH-SY5Y cell death. Collectively, ASIV administration mitigated ZnONPs-induced cytotoxicity in SH-SY5Y cells through restoring mitochondrial quality control process, which hinted the protective role of ASIV in ZnONPs-induced neurotoxicity.

P=N/A, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P=N/A, N=500, Enrolling by invitation, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine | Not yet recruiting --> Enrolling by invitation

ERK1/2 inhibitors may serve as novel molecular-targeted drugs for treating leukemia with NRAS mutations.

Furthermore, the ability of the rejuvenated cells to produce EPO was maintained in hypoxia. Thus, EPO production is controlled by epigenetic mechanisms and hypoxia signaling in the immature state of hypoxic NEP cells.

P1, N=26, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

The impact of ATM on secretory granules confirms previous ATM-null cerebellar transcriptome findings. This study provides the first link of A-T neural atrophy to growth cone collapse and aberrant microtubule dynamics.

The therapeutic vulnerabilities associated with POU2F3 expression in SCLC suggest that a similar approach might be considered for POU2F3-positive carcinomas of the sinonasal tract. Given their diagnostic and possible therapeutic relevance, nNEM have potential to transform the way we approach the diagnosis and management of sinonasal small round epithelial/neuroepithelial malignancies.

While dinutuximab beta immunotherapy is an effective and widely used treatment, it has several potential side effects that must be carefully monitored...However, DFMO has adverse effects that require continuous monitoring. Further research is needed to minimize these side effects and improve its efficacy, particularly in addressing resistance caused by long-term use.

Furthermore, in our zebrafish model, DHE pretreatment effectively alleviated behavioral impairments, reduced neutrophil aggregation, and suppressed neuroinflammation in the brain by regulating TREM2/NF-κB/NLRP3 pathways after intraventricular LPS injection. These findings provide novel insights into the potent protective effects of DHE as a promising novel TREM2 agonist against LPS-induced neuroinflammation, revealing its potential therapeutic role in the treatment of central nervous system diseases associated with neuroinflammation.

Our results suggest OCN as the most plausible neurotoxic agent involved in konzo, while SCN toxicity could be questioned at such high concentrations. Also, they support apoptosis, oxidative stress, and excitotoxicity as probable mechanisms of OCN neurotoxicity.

Genistein helps overcome chemoresistance in various cancers by inhibiting autophagy and promoting apoptosis. It also enhances immunotherapy by boosting immune responses and modifying antigens, but careful dosing is needed when combined with anti-PD-1 treatments to avoid reducing effectiveness.

In conclusion, circ_0004630 knockdown might suppress NSCLC cell proliferation, metastasis, and glycolysis partly by the miR-1208/LRRK2 axis. Our findings hinted at an important theoretical basis for further elucidating the pathogenesis of NSCLC and targeted therapy.