New research suggests that most Alzheimer’s cases may rely on the influence of just one gene.
Category: biotech/medical – Page 31
Tumor-derived aminopeptidase N promotes early stages of brain metastatic colonization
In this study, we identified the aminopeptidase CD13 as a key mediator in a subset of human BrMs originating from breast and lung cancers, with approximately 30% of samples exhibiting cancer cell-specific CD13 expression. Notably, this prevalence aligns with previous reports in breast and lung primary tumors. In BC, CD13 cancer cell expression was documented in 36% of patient samples analyzed, with higher rates in invasive ductal carcinoma,31 while in lung cancer, 35% of patients analyzed were positive for cancer cell CD13 expression.32 These observations suggest that CD13 expression is maintained during metastatic progression to the brain, underscoring its potential as a therapeutic target. Importantly, CD13 expression in primary lung cancer is associated with significantly reduced survival, with a similar trend in BC.31,32 Consistent with these data, we show here that patients with HER2+ BC with CD13high tumors have significantly poorer clinical outcomes. These findings emphasize the importance of stratifying patients by CD13 status to better assess both its prognostic significance and therapeutic potential.
To gain mechanistic insight into CD13 function, we employed murine BrM models from three primary origins (breast, lung, and melanoma) that recapitulate distinct stages of the metastatic cascade. Notably, only the breast-BrM model exhibited robust CD13 expression, suggesting that lung cancer and melanoma may rely on alternative, CD13-independent mechanisms to colonize the brain. CD13 knockdown in breast-BrM cells significantly prolonged survival and reduced metastatic seeding following intracardiac injection. This effect was less pronounced when cancer cells were introduced directly into the brain parenchyma (intracranial injection) or implanted at the primary site (MFP), underscoring CD13’s predominant role during the initial colonization phase of metastasis.
Both gain-and loss-of-function experiments confirmed CD13’s functional importance in metastatic seeding. CD13 has been described as a moonlighting enzyme with diverse cellular functions relevant to regulating metastasis,16,17 including β1 integrin recycling,21 cell migration,21 and activation of the MAPK and PI3K pathways.33 Based on our RNA-seq analysis, CD13 overexpression may further enhance metastatic efficiency through activation of Rho family GTPases and effectors that orchestrate cytoskeletal remodeling, endothelial cell adhesion, and transendothelial migration.34 These features position CD13 as a compelling anti-cancer target; indeed, CD13 inhibition has been explored in several therapeutic development efforts. However, no brain-permeable CD13 inhibitor has yet been approved worldwide for clinical use,16 representing a critical gap in the translational landscape.
Beta-2-Microglobulin Is Bad For Neurogenesis: What’s My Data? (6-Test Analysis)
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China’s ‘Ethnic Specific’ Bio-Weapons Target Specific Races Based on DNA
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Mitochondrial specialization and signaling shape neuronal function
How neuronal function is shaped by mitochondria.
Despite the established links between mitochondrial dysfunction and neuronal disorders, the specialization of mitochondria to support the specific demands of neurons has been less extensively explored.
Proper mitochondrial positioning influences an array of neuronal functions and processes, from neurodevelopment through synaptic transmission, due to the participation of mitochondria as local ATP suppliers, Ca2+ sinks, and sites of neurotransmitter synthesis.
In neurons, mitochondria are also crucial for local translation in axons and dendrites, to which they provide both local ATP and mRNA transport. In this way, mitochondria emerge as centers for neuronal plasticity sciencenewshighlights ScienceMission https://sciencemission.com/Mitochondrial-specialization
Neurons are specialized cells designed to process information and transmit it, often across long distances. In many neurons, the axonal volume far exceeds the somato-dendritic volume, creating a need for long-range transport and local polarization mechanisms. In addition, action potential firing and restoration of ionic gradients, as well as dynamic changes in synaptic plasticity, further increase the energetic demands of neurons. In this review, we highlight the roles mitochondria play in vertebrate neuronal biology and how mitochondrial functionality is tuned to support the unique demands of neurons. We cover the influence of mitochondrial positioning, ATP generation and Ca2+ buffering on neuronal function, and explore the role of mitochondria in neurotransmitter metabolism and local protein translation.
Simple patch can make medications safer and more effective
Vancomycin is the antibiotic doctors reach for when almost nothing else will work. It’s used in hospitals for serious drug-resistant infections, or for when an infection is spreading through the patient’s bloodstream, but it’s also notoriously tricky to dose: too little and it won’t knock out the infection, too much and the patient risks kidney damage or even death. Up to 40% of patients receiving vancomycin develop an acute kidney injury.
Right now, dosage levels are monitored by repeated blood tests, an invasive and time-consuming process that can’t always give clinicians the data they need in time. Hoping to solve this issue, UNSW and international researchers working alongside Australian diagnostics company Nutromics developed a minimally invasive patch that tracks the antibiotic in patients every five minutes.
The team has published the results of a clinical trial in Nature Biotechnology, and say its success demonstrates that the major scientific and safety challenges have been solved.
Enhanced Selenium Supplement Extends Lifespan and Delays Multi‐Organs Aging by Regulating the Sik1 Pathway Through Maintaining Calcium Homeostasis
In healthy aging strategies, nutritional supplements synergize with optimized dietary and lifestyle interventions by modulating aging-related molecular pathways.[ 8, 9 ] Notably, NMN exerts multi-organ anti-aging effects by elevating NAD+ levels to activate the SIRT1 pathway, thereby significantly enhancing mitochondrial function while reducing oxidative stress and DNA damage.[ 10 ] Similarly, curcumin delays aging and related diseases through pleiotropic mechanisms involving oxidative stress regulation, anti-inflammatory actions, telomere maintenance, and sirtuin protein modulation.[ 11 ] However, practical applications face significant challenges: bioactive compounds like resveratrol and curcumin suffer from limited bioavailability due to poor aqueous solubility and first-pass metabolism, while excessive supplementation of antioxidants such as vitamins C/E may disrupt reactive oxygen species (ROS) signaling homeostasis, potentially inducing cellular toxicity or even increasing hemorrhagic risk.[ 12-14 ] Future development of anti-aging supplements should focus on: 1) innovative formulation strategies to enhance bioavailability; 2) optimized dosing regimens to minimize toxicity; and 3) long-term clinical studies to validate efficacy.
Selenium, an essential trace element with diverse biological activities, plays a critical role in healthy aging.[ 15-17 ] ≈1 billion people worldwide are affected by selenium deficiency, which is closely linked to neurological disorders, cardiovascular abnormalities, malignancies, and immune dysfunction.[ 18-20 ] Substantial evidence supports the anti-aging effects of selenium through multiple mechanisms: 1) Selenomethionine (SeMet) effectively suppresses Fe2+/H2O2- or Aβ-induced free radical generation, demonstrating therapeutic potential for Alzheimer’s disease characterized by oxidative stress;[ 21 ] 2) Selenium supplementation elevates serum GPx3 levels, a selenoprotein predominantly localized in the basement membrane of renal proximal tubules, modulating mitochondrial quality control pathways to mitigate heavy metal-induced renal aging;[ 22 ] and 3) Our recent findings reveal that selenium supplementation significantly attenuates age-related muscle atrophy by preserving redox homeostasis and regulating muscle protein metabolism.[ 23 ] Recent clinical trials in patients with advanced non-small cell lung cancer (NSCLC) demonstrated that oral administration of selenium nanoparticles (SeNPs) as a dietary supplement (200 µg day−1) in combination with Bev+AP chemotherapy significantly enhanced therapeutic outcomes compared to chemotherapy alone. The SeNPs combination group showed remarkable tumor regression, with progression disease rates decreasing dramatically from 50% to 0% and partial response rates increasing to 83.3%, along with significantly improved objective response rate and disease control rate.[ 24 ] Importantly, this regimen maintained excellent safety profiles without triggering fluctuations in pro-inflammatory or immunosuppressive cytokines. These compelling findings not only establish SeNPs as a safe and effective adjuvant therapy for advanced NSCLC but also provide valuable clinical translation data for nano-selenium formulations in oncology. Despite selenium’s proven benefits in reducing oxidative damage, maintaining genomic stability, and delaying telomere shortening, its narrow therapeutic window, limited bioavailability, and specific mechanisms in multi-organ protection during natural aging require further investigation.
Nanodelivery carriers have emerged as a next-generation platform for gene and drug delivery, offering tunable physicochemical properties such as size, composition, and surface modifications.[ 25 ] Our team has developed organically-bridged mesoporous silica nanoparticles (MSNs) by incorporating functional diselenide bonds into the silica framework at the molecular level, addressing the critical challenge of poor biodegradability in conventional silica materials.[ 26 ] This nanocarrier exhibits unique dual redox-responsive properties, allowing for more precise maintenance of redox homeostasis compared to traditional antioxidants, aligning with the core goal of preserving organismal homeostasis in anti-aging research. Building on this breakthrough, a comprehensive research framework was established: first, this study constructed a natural aging mouse model with MSNs, disulfide-bridged MSNs (SMSNs), commercially available SeMet as controls and then compared the effects of diselenide-bridged MSNs (SeMSNs) on lifespan extension, frailty delay, and multi-organ anti-aging. Next, key pathways and targets were identified through multi-organ transcriptome sequencing, followed by in-depth mechanistic studies. Finally, clinical translation was integrated by analyzing the correlation between serum selenium levels and aging biomarkers in the elderly, and validating the clinical effects of SeMSNs using primary adipose precursor cells (APCs) models. This systematic approach provides a solid theoretical foundation and clinical evidence for the application of nano-selenium in anti-aging research.