Ontosight^® Newsletter Issue 19

Ontosight^® – Newsletter
January 27^th – February 9^th, 2025 – Issue 19

Welcome to the 19^th edition of Ontosight^® Newsletter! We're excited to introduce Ontosight.ai—our free AI research assistant now powered by DeepSeek R1—that streamlines your research with smart, conversational insights.

This issue also highlights breakthrough cancer studies revealing novel immunotherapy strategies and targeted treatments, alongside pioneering neurology research exploring gut-brain connections in Alzheimer's and depression. Discover how AI and emerging therapies are revolutionizing precision medicine, with innovative approaches for metabolic, autoimmune, and infectious diseases—all complemented by key regulatory updates shaping healthcare.

Product Spotlight: Introducing Ontosight.ai – Your Research Companion for Smarter, Faster Insights

Ontosight.ai is our latest cutting-edge research and AI-powered Q&A platform designed to transform the way you access, analyze, and apply scientific information. Whether you’re an undergraduate, a Ph.D. student, or a seasoned researcher, this platform makes every inquiry feel like a conversation with a subject-matter expert. Here’s what you need to know:

Key Features

• Conversational Search: Ask questions naturally—like “What are the most effective cancer treatments?”—and receive clear, concise, and tailored answers.
• Transparent Citations & Sources: Every response includes full references from trusted journals, academic papers, and specialized databases, ensuring the accuracy you need for scholarly work.
• Specialized for Life Sciences & Beyond: Dive deep into biomedical studies, clinical trials, genomics, bioinformatics, and more—all on one intuitive platform.
• Knowledge Synthesis: Not just raw data—the platform distills key insights, connecting interdisciplinary dots to spark innovation.
• Enhanced Efficiency: Save hours with actionable summaries, real-time answers, and highlighted key points that keep you focused on your research goals.
• User-Friendly Experience: A clean interface with features like contextual summaries, glossaries, and an easy-to-use design ensures accessibility for everyone.

Powered by NVIDIA: Ontosight.ai is backed by advanced NVIDIA technology, ensuring optimal performance and scalability.

Growing Academic & Research Partnerships

We’re proud to announce significant milestones that underscore the global traction of Ontosight.ai:

• Academic Collaborations: We’ve signed MoUs with leading institutions like Symbiosis Institute of Technology and MIT World Peace University in Pune, and extended access to the Business School at Universidade Federal do Pampa in Brazil.
• Global Showcases: Recently, Ontosight.ai was showcased at the GPU Meetup hosted by IIT Kanpur, and it’s been featured in the Product Hunt Newsletter.
• University Engagements: Our platform has also been presented to faculty at Pimpri Chinchwad University, Pune, demonstrating its potential to enhance academic research.

DeepSeek R1 Now on Ontosight.ai – For Free!

We’re excited to announce that DeepSeek R1—our advanced AI engine—is now available at no cost for all users. This major update means:

• Free Access for All: Unlock powerful, AI-driven insights without any barriers.
• Smarter Citations & Structured Responses: Enjoy even more accurate references and clearer, well-organized outputs.
• Google Sign-In Integration: Get started instantly—no lengthy sign-up process required.

Why It Matters:

• Accelerate Discoveries: Analyze vast datasets in seconds, making breakthroughs faster than ever.
• Data-Backed Decisions: Rely on AI-curated insights that save you time while ensuring precision.
• The Future is Now: As AI becomes an integral part of everyday research, tools like DeepSeek R1 are paving the way for smarter, more efficient problem-solving.

Ready to transform your research experience? Sign up today at Ontosight.ai and explore the future of discovery.

Featured Articles

1. Cutting-Edge Cancer Research & Immunotherapy

• Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins

This study shows that cancer cells evade immune-mediated ferroptosis by upregulating Fabp7, which reprograms lipid metabolism and disrupts circadian regulation in immune cells. Fabp7 reduces lipid peroxidation, enhances mitochondrial function, and promotes tumor survival. Targeting Fabp7 could improve immunotherapy outcomes by re-sensitizing tumors to ferroptosis. [Article]

• A neoantigen vaccine generates antitumour immunity in renal cell carcinoma

A phase I trial tested a personalized cancer vaccine (PCV) in high-risk renal cell carcinoma (RCC) patients, showing strong immune responses against tumor driver mutations. All nine patients remained recurrence-free after a median follow-up of 40.2 months, with no severe side effects. The vaccine induced durable T cell expansion and tumor recognition, highlighting its potential as an effective adjuvant therapy for RCC. [Article]

• Lymphatic-Derived Oxysterols Promote Anti-Tumor Immunity and Response to Immunotherapy in Melanoma

This study reveals that lymphatic endothelial cells (LECs) in melanoma upregulate Ch25h, producing 25-hydroxycholesterol (25-HC), which inhibits immunosuppressive macrophages and promotes proinflammatory immune responses. In human melanoma, Ch25h expression correlates with better survival and improved immunotherapy response. Targeting this pathway could enhance immunotherapy efficacy by boosting anti-tumor immunity. [Article]

• The Mode of Action and Clinical Outcomes of Sacituzumab Govitecan in Solid Tumors

Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate approved for metastatic triple-negative and HR+/HER2- breast cancer, with potential in other tumors. It delivers SN-38, a topoisomerase I inhibitor, to Trop-2+ tumor cells, inducing apoptosis and a bystander effect. SG has shown broad efficacy, with manageable neutropenia and diarrhea as common adverse effects. [Article]

• EGFR Inhibition Boosts the Efficacy of NAT10 Inhibitor Remodelin in Colorectal Cancer

This study identifies NAT10 as a pro-oncogenic factor in colorectal cancer (CRC) that stabilizes ERRFI1 mRNA via ac4C modifications, leading to EGFR pathway activation. While NAT10 inhibition alone had limited effects, combining the NAT10 inhibitor Remodelin with cetuximab and 5-Fluorouracil enhanced tumor regression in CRC models with wild-type KRAS, NRAS, and BRAF. This triple therapy offers a promising strategy for CRC treatment. [Article]

2. Neurology & Neurodegenerative Diseases

• Bioaccumulation of microplastics in decedent human brains

This study confirms the presence of microplastics and nanoplastics (MNPs), primarily polyethylene, in human kidney, liver, and brain tissues. Brain tissues showed higher polyethylene levels, with increasing MNP accumulation over time. Notably, brains with dementia had greater MNP deposition, particularly in cerebrovascular walls and immune cells, underscoring the need to investigate the health impacts of plastic exposure. [Article]

• Multi-omics analyses identify gut microbiota-fecal metabolites-brain-cognition pathways in the Alzheimer's disease continuum

This study links gut microbiota dysbiosis to Alzheimer's disease (AD) through changes in microbial composition, fecal metabolites, brain structure, and cognition. Key microbial taxa and metabolites progressively changed from healthy controls to mild cognitive impairment to AD. Multi-omics integration revealed mediation pathways where microbiota influence cognition via metabolites and neuroimaging. These findings highlight potential therapeutic targets in the gut-brain axis for AD. [Article]

• Microglia-Derived Interleukin-6 Triggers Astrocyte Apoptosis in the Hippocampus and Mediates Depression-Like Behavior

This study identifies microglial IL-6 as a key driver of astrocyte atrophy and apoptosis in a depression model induced by chronic social defeat stress (CSDS). Blocking IL-6 signaling or inhibiting microglial activation reduced astrocyte loss and alleviated depression-like behaviors. These findings highlight the IL-6/IL-6R pathway as a potential therapeutic target for major depressive disorder. [Article]

3. AI, Emerging Technologies and Innovative Therapies

• Deep learning to decode sites of RNA translation in normal and cancerous tissues

RiboTIE is a transformer-based model designed to enhance ribosome profiling analysis by directly leveraging raw ribosome profiling counts to detect translated open reading frames (ORFs) with high precision and sensitivity. It successfully identifies RNA translation variations in both normal brain and medulloblastoma samples, offering novel insights into protein synthesis regulation. RiboTIE improves Ribo-Seq data analysis, advancing our understanding of translation dynamics in health and disease. [Article]

• Screening Performance and Characteristics of Breast Cancer Detected in the Mammography Screening With Artificial Intelligence Trial (MASAI)

This study demonstrates that AI-supported mammography screening enhances cancer detection while reducing radiologists' workload. AI detected more invasive and in situ cancers, particularly smaller, lymph-node-negative, and high-grade tumors, compared to standard double reading. Despite improved detection, recall and false-positive rates remained similar, and AI increased the positive predictive value of recall. Additionally, AI reduced screen-reading workload by 44.2%, highlighting its potential to optimize breast cancer screening efficiency without compromising accuracy. [Article]

• An AI-assisted morphoproteomic approach is a supportive tool in esophagitis-related precision medicine

This study used proteomic profiling and machine learning to identify distinct molecular signatures for different types of esophagitis, improving diagnostic accuracy. The AI-assisted approach successfully differentiated conditions like GERD, EoE, Crohn’s, HSV, and Candida esophagitis with high precision. In a case study, it revised a GERD diagnosis to Crohn’s and suggested a personalized treatment. This method enhances precision medicine in esophagitis diagnosis and management. [Article]

• Gene-Replacement Therapy in Neurodevelopmental Disorders: Progress and Challenges

This study explores gene-replacement therapy for SLC6A1-related neurodevelopmental disorders using AAV9 vectors in mouse models. Early postnatal intrathecal delivery of GAT1 showed high expression and was well tolerated, while later-stage treatment was ineffective. The findings highlight the critical role of early GABA metabolism and the importance of timely gene therapy intervention. [Article]

4.Metabolic & Autoimmune Disorders

• Lipidomics unravels lipid changes in osteoarthritis articular cartilage

This study maps the lipid composition of human articular chondrocytes (hACs) and identifies OA-associated lipidome changes. OA chondrocytes showed increased ceramides and reduced cholesteryl esters, triacylglycerols, and odd-chain fatty acids like C17:0. A deficiency in HACL1, an enzyme crucial for odd-chain fatty acid synthesis, shifted hACs to a catabolic state. These findings suggest targeting lipid imbalances as a potential OA therapy. [Article]

• Estrogen-dependent activation of TRX2 reverses oxidative stress and metabolic dysfunction associated with steatotic disease

This study explores the protective role of estrogens in metabolic dysfunction-associated steatotic liver disease (MASLD). Estrogen treatment in steatotic liver cells reduced oxidative stress, lipid accumulation, and mitochondrial dysfunction by upregulating mitochondrial thioredoxin 2 (TRX2). Disrupting TRX2 negated these benefits, suggesting a key mechanism through which estrogens may slow MASLD progression. [Article]

• Associations Between Diabetic Retinopathy and Frailty: Insights From the National Health and Nutrition Examination Survey

This study found that diabetic retinopathy (DR) is significantly associated with an increased risk of frailty, with a moderate genetic correlation. DR appears to accelerate physical decline rather than being influenced by frailty itself. These findings emphasize the need for integrated care, including frailty screening, to improve health outcomes in individuals with DR. [Article]

5. Infectious Diseases & Immunology

• Pre-exposure antibody prophylaxis protects macaques from severe influenza

This study demonstrates that pre-exposure prophylaxis with the broadly neutralizing antibody (bnAb) MEDI8852 effectively protects cynomolgus macaques from severe disease caused by aerosolized H5N1 infection. Protection was dose-dependent but did not rely on Fc-mediated functions. These findings suggest bnAbs like MEDI8852 could offer broad protection against future pandemic influenza A viruses. [Article]

• VANGL2 alleviates inflammatory bowel disease by recruiting the ubiquitin ligase MARCH8 to limit NLRP3 inflammasome activation through OPTN-mediated selective autophagy

This study identifies VANGL2 as a key regulator in inflammatory bowel disease (IBD) by inhibiting NLRP3 inflammasome activation. VANGL2 deficiency worsens colitis in mice and enhances inflammation in IBD patients. Mechanistically, VANGL2 promotes NLRP3 degradation via autophagy, and its loss leads to sustained inflammation. Targeting this pathway may offer new therapeutic strategies for IBD. [Article]

• Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1

This study explores the potential of repurposing domperidone, an antiemetic, to combat dengue virus (DENV) infection. Domperidone binds to viral envelope (E) and nonstructural protein 1 (NS1), inhibiting viral RNA replication and NS1 secretion in human hepatocyte-like cells. Its antiviral effects were observed across all four DENV serotypes, highlighting its potential as a therapeutic candidate. [Article]

Additional Highlights

Explore more groundbreaking research and regulatory updates in our biweekly newsletter:

• Clioquinol inhibits angiogenesis by promoting VEGFR2 degradation and synergizes with AKT inhibition to suppress triple-negative breast cancer vascularization [Article]
• A BCL-xL/BCL-2 PROTAC Effectively Clears Senescent Cells in the Liver and Reduces MASH-Driven Hepatocellular Carcinoma in Mice[Article]
• Update on Regulatory Review of Lecanemab for Early Alzheimer’s Disease in the European Union[News]
• Sonnet BioTherapeutics Further Expands Global Intellectual Property Portfolio with Issuance of EU Patent for FHAB® Platform Technology[News]
• Pfizer Launches PfizerForAll™, a Digital Platform that Helps Simplify Access to Healthcare[News]
• Supernus Announces Label Update for Non-Stimulant ADHD Treatment, Qelbree®, Including New Pharmacodynamic Data and Information for Breastfeeding Women[News]
• Vistagen Receives U.S. Patent for AV-101 to Treat Neuropathic Pain[News]

Stay informed about the latest in medical research and innovation. Join us in two weeks for more insights into the dynamic world of healthcare and life sciences advancements.

Ontosight^® – Biweekly Newsletter brings you the top and trending articles on medical advancements and life sciences. Subscribe now to stay updated on the latest breakthroughs and innovations in healthcare.

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