Ontosight^® Newsletter Issue 4

Ontosight^® – Newsletter
July 1^st – July 14^th, 2024 – Issue 4

Trending Topic: Medical Advancements and Therapeutic Strategies

Welcome to the 4^th edition of Ontosight^® Newsletter! This issue, we spotlight major advancements in medical research, from AI-driven innovations in cancer diagnostics to groundbreaking cancer therapies and genetic discoveries. We also delve into neuroscience breakthroughs and novel approaches in diabetes and metabolic disorders, underscoring the transformative impact of these developments on healthcare.

Featured Articles

1. Artificial Intelligence and Innovative Approaches in Medical Research

• Artificial Intelligence-based Segmentation of Residual Pancreatic Cancer in Resection Specimens Following Neoadjuvant Treatment (ISGPP-2): International Improvement and Validation Study

Neoadjuvant therapy (NAT) for borderline resectable pancreatic cancer necessitates evaluating residual pancreatic cancer (RPC) in resection specimens. This study developed and validated the first automated segmentation model using artificial intelligence to quantify RPC. Digitized histopathological slides from 528 patients across 14 centers worldwide were used to train a U-Net model, achieving robust mean F1 scores in cross-validation. The ISGPP model, which demonstrated strong performance in detecting RPC, is now publicly available for objective evaluation of NAT response in pancreatic cancer. [Article]

• A deep learning-driven discovery of berberine derivatives as novel antibacterial against multidrug-resistant Helicobacter pylori

Helicobacter pylori, a major cause of gastric cancer, is difficult to treat due to its prevalence and drug resistance. A deep learning model identified a berberine derivative, 8, which showed strong efficacy against H. pylori with minimum inhibitory concentrations of 0.25–0.5 μg/mL. Pharmacokinetic studies confirmed its excellent gastric retention, and it significantly reduced bacterial load, comparable to traditional therapies, without disturbing the intestinal flora. SecA and BamD were identified as direct targets, making 8 a promising candidate for treating drug-resistant H. pylori. [Article]

• Machine Learning-based Framework Develops a Tumor Thrombus Coagulation Signature in Multicenter Cohorts for Renal Cancer

Renal cell carcinoma (RCC) with venous tumor thrombus has a poor prognosis, and current staging systems are inadequate for guiding treatment. This study developed a coagulation tumor thrombus signature (TTCRRS) using machine learning, comprising 10 prognostic genes. The TTCRRS accurately predicted survival outcomes and therapy responses, outperforming existing signatures. It complements traditional staging systems, offering better precision in treatment options. [Article]

2. Groundbreaking Cancer Research

• Next-Gen Breast Cancer Treatment: Copper-based composites nanoparticles improve triple-negative breast cancer treatment with induction of apoptosis-cuproptosis and immune activation

Combining apoptosis, cuproptosis, and immune activation offers a promising strategy against triple-negative breast cancer (TNBC). Two prodrugs, PEG-TK-DOX and PEG-DTPA-SS-CPT, self-assemble with Cu2+ to form PCD@Cu, releasing doxorubicin (DOX), camptothecin (CPT), and Cu+ in response to elevated ROS and GSH in TNBC cells. This induces apoptosis, immunogenic cell death (ICD), and downregulates ATP7B, leading to copper ion accumulation and cuproptosis. In vitro and in vivo studies confirm PCD@Cu’s strong anti-tumor efficacy and excellent biosafety. [Article]

• Game-Changing Prostate Cancer Study: Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer

This study examined cancer evolution in locally advanced prostate cancer using genomic and deep learning analyses of 642 samples and 1,923 histological sections. Both genetic and morphological diversity independently predicted recurrence, with their combination identifying high-risk patients. Spatial segregation of clones and chromosome 6p loss also indicated recurrence risk and reduced immune infiltration. Combining genomics with AI-enhanced histopathology revealed crucial biomarkers of cancer evolution and progression. [Article]

• Unlocking the diagnostic power of plasma extracellular vesicle miR-200 family in pancreatic ductal adenocarcinoma

This study aimed to differentiate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary diseases using plasma extracellular vesicle (EV)-derived miRNAs. EVs were isolated and characterized, and small RNA sequencing identified the miR-200 family as significantly overexpressed in PDAC. Validation in an independent cohort demonstrated the EV-miR-200 model had high diagnostic accuracy with 100% sensitivity and 88% specificity. This study is the first to validate EV-miR-200 as a potential biomarker for PDAC, with further validation needed in larger trials. [Article]

3. Game-Changing Genetic and Molecular Discoveries

• Loss of Lamin A leads to the nuclear translocation of AGO2 and compromised RNA interference

In mammals, RNA interference (RNAi) is typically studied in the cytoplasm, but AGO proteins are also found in the nucleus. This study found that reduced Lamin A levels increase nuclear AGO2 in neuroblastoma and melanoma cells, which usually lack nuclear AGO2. Lamin A loss leads to EGFR and Src kinase activation, which affects AGO2 stability and decreases nuclear RNAi activity by about 60%. Additionally, AGO2 interacts with FAM120A in the nucleus, which inhibits RNAi and supports cancer cell proliferation. [Article]

• Genomic profiling of a multi-lineage and multi-passage patient-derived xenograft biobank reflects heterogeneity of ovarian cancer

A resource of 68 early passage patient-derived xenografts (PDXs) was developed from 65 pediatric solid tumors. Genomic analysis showed about 30% of PDXs and patient tumors (PTs) have low mutational similarity, with aggressive subclones in PTs seeding the major clone in PDXs, likely due to immune suppression. PDXs generally replicate PT copy number and transcriptomic profiles. The gene fusion LRPAP1-PDGFRA, was also identified highlighting immune constraints’ role in tumor evolution and the utility of this PDX resource for childhood cancer research. [Article]

• CRISPR-Cas gene editing: applications in genetic disease therapy and research

This paper reviews CRISPR/Cas9 gene-editing technology for precisely treating diseases by correcting mutations or disrupting disease genes. It highlights the challenge of delivering CRISPR systems in vivo and suggests nonviral vectors with target recognition as a future research focus. The review covers advancements in gene-editing methods, delivery vectors, and disease characteristics, summarizes successful clinical trials, and discusses current challenges in CRISPR/Cas9 applications. [Article]

4. Neuroscience and Mental Health Breakthroughs

• SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system in vitro

SARS-CoV-2 is associated with neurological issues like hemorrhage and encephalitis, but the mechanism is unclear. This study detected ACE2 and TMPRSS2 in brain cells, including astrocytes and neurons, which support productive SARS-CoV-2 infection. Infected cells released virus particles, while brain microvascular endothelial cells, pericytes, and microglia did not. These results suggest SARS-CoV-2 directly infects neural cells, potentially explaining neurological symptoms of COVID-19. [Article]

• Screen Media Use and Mental Health of Children and Adolescents

This study assessed the effects of a 2-week screen media reduction on children’s and adolescents’ mental health. Involving 89 families and 181 children, the intervention group, which reduced screen time to 3 hours per week, showed significant improvements in behavioral difficulties, internalizing symptoms, and prosocial behavior compared to the control group. Results suggest that reducing screen media use can positively impact mental health. Further research is needed to determine if these effects are sustained long-term. [Article]

• Therapeutic potential of exercise-hormone irisin in Alzheimer’s disease

Irisin, a myokine produced from FNDC5 in response to exercise, has shown promise in protecting against Alzheimer’s disease by improving cognitive function and reducing amyloid-β and tau pathologies. It appears to enhance neprilysin activity, which helps degrade amyloid-β. Despite these findings, more research is needed to clarify irisin’s potential as a therapeutic target for Alzheimer’s. This overview summarizes irisin/FNDC5’s protective roles and mechanisms against the disease. [Article]

5. Innovations in Diabetes and Metabolic Disorders

• Telemedicine in Improving Glycemic Control Among Children and Adolescents With Type 1 Diabetes Mellitus

This meta-analysis of 20 RCTs found that telemedicine significantly reduced HbA1c levels by 0.22% in children and adolescents with Type 1 diabetes compared to usual care. It also improved non-youth-specific quality of life, though other outcomes like self-monitoring and hypoglycemia were not significantly affected. Benefits were greater with shorter study durations, smartphone apps, and medication adjustments. Telemedicine is a promising addition to usual care, but more research is needed on its long-term effects and cost-effectiveness. [Article]

• Gut microbiota and immune modulation in metabolic-associated fatty liver disease

Metabolic-associated fatty liver disease (MAFLD) is increasingly common due to lifestyle and dietary factors, posing significant health and economic challenges. Advances in 16S sequencing and multi-omics have highlighted the gut microbiota’s role in MAFLD, influencing digestion, metabolism, and immune regulation. The gut-liver axis is crucial in MAFLD, with gut-derived toxins affecting liver function and vice versa. This review discusses gut microbiota characteristics in MAFLD, including its impact on bile acid circulation, metabolism, and treatment strategies targeting the microbiota. [Article]

• Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes

This study investigated the risk of 13 obesity-associated cancers (OACs) in patients with type 2 diabetes (T2D) prescribed GLP-1 receptor agonists (GLP-1RAs) compared to those on insulin or metformin. The analysis of over 1.6 million patients showed that GLP-1RAs significantly reduced the risk of 10 out of 13 OACs, including gallbladder, meningioma, pancreatic, and hepatocellular cancers, compared to insulin. GLP-1RAs did not show a reduced risk for postmenopausal breast or thyroid cancers and had an increased risk for kidney cancer compared to metformin. These findings suggest GLP-1RAs may have potential benefits in reducing cancer risk among high-risk T2D populations, warranting further research. [Article]

Additional Highlights

Explore more groundbreaking research and guidelines in our newsletter:

• Efficacy of Melatonin Administration in Reducing Headaches in Children with Migraines without Sleep Disorders [Article]
• Microbiota and Resveratrol: How Are They Linked to Osteoporosis? [Article]
• Hong Kong approves Leqembi for Alzheimer’s treatment [News]
• Arcutis bags FDA approval for atopic dermatitis cream after delay [News]
• AstraZeneca’s Tagrisso plus chemotherapy wins EU approval for NSCLC [News]
• China NMPA approves Antengene’s Xpovio as monotherapy to treat relapsed or refractory diffuse large B-cell lymphoma [News]
• GSK and MVV launch malaria medicine in Brazil and Thailand [News]
• FDA Rejects Novo’s Once-Weekly Insulin Injection, Cites Manufacturing Process [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.

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