Blocking nitric oxide production for glioblastoma: A targeted therapeutic approach DOI
Shashank Kumar Ojha, Wisam Bazbaz, Manish Kumar Tripathi

и другие.

Brain medicine :, Год журнала: 2025, Номер unknown, С. 1 - 9

Опубликована: Май 20, 2025

Glioblastoma (GBM) represents the foremost prevalent and aggressive form of primary brain tumor, characterized by high morbidity mortality rates. Nitric oxide (NO) has been shown to have diverse effects on various cancers, including GBM. Our previous study NO synthase (NOS) hyperactivation in GBM cell lines. survival was reversed NOS-targeting pharmacological inhibition vitro. The current work explores impact inducible neuronal NOS (iNOS nNOS) inhibitors, BA-103 BA-101, respectively, a glioblastoma xenograft model. Both agents mitigate nitrosative stress through distinct mechanisms. NOD-SCID mice were used establish subcutaneous tumor model with U-87 MG cells. BA-101 administered via intraperitoneal injections. Tumor metrics, weight volume, assessed. Immunofluorescence Western blots conducted assess stress, proliferation, death. Treatment particularly significantly reduced volume A dose-dependent identified 80 mg/kg as most efficacious dose for treatment. Combining antitumor drug temozolomide (TMZ) synergistically size increased survivability bearing TMZ-sensitive findings suggest that targeting nNOS holds promise therapeutic strategy

Язык: Английский

Shared early molecular mechanisms revealed in P301S and 5xFAD Alzheimer’s disease mouse models DOI Creative Commons

Huda Suloh,

Shashank Kumar Ojha,

Maryam Kartawy

и другие.

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Март 26, 2025

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by early molecular events that influence progression. Still, mechanisms caused different mutations of AD are not understood. We have performed a multidisciplinary study to investigate and compare stages pathology in two transgenic mouse models: P301S 5xFAD. Using SNOTRAP-based mass spectrometry, we assessed changes S-nitrosylation, nitric oxide-mediated post-translational modification, proteins both models during their juvenile age. The increased levels 3-nitrotyrosine confirmed nitrosative stress mutant mice. Systems biology analysis revealed shared processes between models, particularly γ-aminobutyric acid (GABA)ergic glutamatergic neurotransmission processes. In model, identified 273 S-nitrosylated (SNOed) cortex, with 244 uniquely SNOed diseased 5xFAD 309 were identified. found altered expression glutamate/GABA-related markers cortex hippocampus models. Additionally, phosphorylation mTOR signaling components hyperactivation this pathway Conversely, mice showed no significant except for elevated ribosomal protein S6 cortex. Our findings key stages. These could serve as potential biomarkers therapeutic targets early-stage AD.

Язык: Английский

Процитировано

0
Multi-omics study reveals differential expression and phosphorylation of autophagy-related proteins in autism spectrum disorder DOI Creative Commons

Eden Deri,

Shashank Kumar Ojha,

Maryam Kartawy

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 29, 2025

Our multi-omics study investigated the molecular mechanisms underlying autism spectrum disorder (ASD) using Shank3Δ4–22 and Cntnap2−/− mouse models. Through global- phospho- proteomics of cortex, we focused on shared changes found that autophagy was particularly affected in both Global identified a small number differentially expressed proteins significantly impact postsynaptic components synaptic function, including key pathways such as mTOR signaling. Phosphoproteomics revealed unique phosphorylation sites autophagy-related ULK2, RB1CC1, ATG16L1, ATG9, suggesting altered patterns contribute to impaired autophagic flux ASD. SH-SY5Y cells with SHANK3 gene deletion showed elevated LC3-II p62 levels, indicating autophagosome accumulation initiation, while reduced level lysosomal activity marker LAMP1 suggested autophagosome-lysosome fusion. The highlights involvement reactive nitrogen species nitric oxide (NO) disruption. Importantly, inhibition neuronal NO synthase (nNOS) by 7-NI normalized markers levels primary cultured neurons. We have previously shown nNOS improved behavioral phenotypes reveals differential expression ASD but further investigation is needed prove full underscores need for examination into functional consequences sites, which may offer potential novel therapeutic targets treatment.

Язык: Английский

Процитировано

0
Oxidative Stress Response and NRF2 Signaling Pathway in Autism Spectrum Disorder DOI Creative Commons
Sergio Davinelli, Alessandro Medoro, Martina Siracusano

и другие.

Redox Biology, Год журнала: 2025, Номер 83, С. 103661 - 103661

Опубликована: Май 2, 2025

Язык: Английский

Процитировано

0
Blocking nitric oxide production for glioblastoma: A targeted therapeutic approach DOI
Shashank Kumar Ojha, Wisam Bazbaz, Manish Kumar Tripathi

и другие.

Brain medicine :, Год журнала: 2025, Номер unknown, С. 1 - 9

Опубликована: Май 20, 2025

Glioblastoma (GBM) represents the foremost prevalent and aggressive form of primary brain tumor, characterized by high morbidity mortality rates. Nitric oxide (NO) has been shown to have diverse effects on various cancers, including GBM. Our previous study NO synthase (NOS) hyperactivation in GBM cell lines. survival was reversed NOS-targeting pharmacological inhibition vitro. The current work explores impact inducible neuronal NOS (iNOS nNOS) inhibitors, BA-103 BA-101, respectively, a glioblastoma xenograft model. Both agents mitigate nitrosative stress through distinct mechanisms. NOD-SCID mice were used establish subcutaneous tumor model with U-87 MG cells. BA-101 administered via intraperitoneal injections. Tumor metrics, weight volume, assessed. Immunofluorescence Western blots conducted assess stress, proliferation, death. Treatment particularly significantly reduced volume A dose-dependent identified 80 mg/kg as most efficacious dose for treatment. Combining antitumor drug temozolomide (TMZ) synergistically size increased survivability bearing TMZ-sensitive findings suggest that targeting nNOS holds promise therapeutic strategy

Язык: Английский

Процитировано

0