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Category: biotech/medical – Page 260

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.

The Wnt–NAD+ axis in cancer, aging, and tissue regeneration

Wnt–NAD+ axis in stem cell function.

The Wnt–NAD+ axis is a fundamental regulatory hub in which metabolic state meets developmental signaling and it acts as a metabolic sensor that coordinates tissue regeneration with cellular energy status through compartment specific NAD+ pools.

Wnt signaling regulates NAD+ metabolism by controlling the expression of key biosynthetic enzymes and NAD+ consumers, while NAD+-dependent proteins modulate Wnt activity through direct interactions and epigenetic modifications.

Sirtuins exhibit tissue-specific and subcellular compartment-dependent roles in Wnt regulation where they function as activators or suppressors depending on the cellular bioenergetic state.

The Wnt–NAD+ axis maintains stem cell function and self-renewal capacity through metabolic/signaling integration, and its disruption during aging leads to declining regenerative capacity.

The progressive dysregulation of compartment-specific Wnt–NAD+ coordination contributes to stem cell exhaustion and multiple pathological conditions, indicating that therapeutic strategies must consider tissue-specific and subcellular targeting. sciencenewshighlights ScienceMission https://sciencemission.com/Wnt%E2%80%93NAD-axis

Continue reading “The Wnt–NAD+ axis in cancer, aging, and tissue regeneration” | >

MIT’s new brain tool could finally explain consciousness

Although the technology has been around for several years, it has not yet become a standard tool in neuroscience research. Now, two researchers at MIT are preparing new experiments using the technique and have published a paper that serves as a detailed guide, or “roadmap,” for applying it to the study of consciousness.

“Transcranial focused ultrasound will let you stimulate different parts of the brain in healthy subjects, in ways you just couldn’t before,” says Daniel Freeman, an MIT researcher and co-author of the paper. “This is a tool that’s not just useful for medicine or even basic science, but could also help address the hard problem of consciousness. It can probe where in the brain are the neural circuits that generate a sense of pain, a sense of vision, or even something as complex as human thought.”

Unlike other brain stimulation methods, transcranial focused ultrasound does not require surgery. It can reach deeper areas of the brain with greater precision than techniques such as transcranial magnetic or electrical stimulation.

The layer 6b theory of attention

(A) Neuromodulatory projections of the ascending arousal system project divergent axons across the cortex, including to L6b, providing state-dependent signals. Likewise, higher-order cortical axons project to multiple cortical regions, including L6b, providing top-down volitional signals. L6b integrates the convergent input from these two pathways and directs its output to CTC loops with fast and focused activation.

(B) L6b is depolarized by arousal-promoting neuromodulators (left), and we hypothesize that the addition of higher-order cortical feedback strongly activates L6b (right). Thus, the role of neuromodulation is to bring L6b close to the activation threshold across the cortex so that specific L6b circuits can be more easily recruited by specific top-down cortical input. ACh, acetylcholine; 5HT, serotonin; DA, dopamine; NA, noradrenaline; HIS, histamine.

Immune gene diversity and STING1 variants in shaping cancer immunity across different genetic ancestry populations

Hu et al. analyzed non-synonymous SNPs across diverse human populations and revealed divergent evolutionary pressures on immune-and cancer-related genes. By integrating population diversity with functional evaluation, they identified STING1 variants as modulators of interferon signaling. Their findings suggest that germline variations shaped by genetic ancestry may influence cancer immunity.

PRISM reanalyzes 4,400 tumors, reshaping the debate over tumor microbiomes

When scientists sequence tumor DNA, they typically find small amounts of genetic code from bacteria, viruses and fungi—microorganisms that—if actually present in tumor tissues—could influence how they grow, evade immunity or respond to treatment. But do microorganisms truly reside in tumors, or do the samples become contaminated before sequencing occurs?

Independent analyses of the same genomic data have reached wildly different conclusions. Now, researchers at Rutgers Cancer Institute have developed a computational tool that settles the controversy by distinguishing genuine microbial signals from artifacts. Their findings are published in Cancer Cell.

“There are microbes all over the environment, on our skin and in our breath,” said Subhajyoti De, a member of the Genomic Instability and Cancer Genetics Program at Rutgers Cancer Institute and the senior author of the study. “There could be DNA particles floating in the air. How do you know whether you’re finding came from the tissue you were interested in, or whether something was introduced along the way?”

Ultrastructural and Histological Cryopreservation of Mammalian Brains by Vitrification

Studies of whole brain cryopreservation are rare but are potentially important for a variety of applications. It has been demonstrated that ultrastructure in whole rabbit and pig brains can be cryopreserved by vitrification (ice-free cryopreservation) after prior aldehyde fixation, but fixation limits the range of studies that can be done by neurobiologists, including studies that depend upon general molecular integrity, signal transduction, macromolecular synthesis, and other physiological processes. We now show that whole brain ultrastructure can be preserved by vitrification without prior aldehyde fixation. Rabbit brain perfusion with the M22 vitrification solution followed by vitrification, warming, and fixation showed an absence of visible ice damage and overall structural preservation, but osmotic brain shrinkage sufficient to distort and obscure neuroanatomical detail. Neuroanatomical preservation in the presence of M22 was also investigated in human cerebral cortical biopsies taken after whole brain perfusion with M22. These biopsies did not form ice upon cooling or warming, and high power electron microscopy showed dehydrated and electron-dense but predominantly intact cells, neuropil, and synapses with no signs of ice crystal damage, and partial dilution of these samples restored normal cortical pyramidal cell shapes. To further evaluate ultrastructural preservation within the severely dehydrated brain, rabbit brains were perfused with M22 and then partially washed free of M22 before fixation. Perfusion dilution of the brain to 3-5M M22 resulted in brain re-expansion and the re-appearance of well-defined neuroanatomical features, but rehydration of the brain to 1M M22 resulted in ultrastructural damage suggestive of preventable osmotic injury caused by incomplete removal of M22. We conclude that both animal and human brains can be cryopreserved by vitrification with predominant retention of ultrastructural integrity without the need for prior aldehyde fixation. This observation has direct relevance to the feasibility of human cryopreservation, for which direct evidence has been lacking until this report. It also provides a starting point for perfecting brain cryopreservation, which may be necessary for lengthy space travel and could allow future medical time travel.

The authors have declared no competing interest.

What to watch as fungal infections rise: Species that can quickly ‘translate’ fat-use proteins

A new study by researchers at Kiel University and MPI-EvolBio describes how more efficient protein production drives the adaptation of fungi to the human body, potentially turning previously harmless species into emerging pathogens. In the wake of global change and the associated rise in temperatures, fungal infections are on the increase worldwide, threatening crops, wildlife and, also, human health. Many fungal species are completely harmless and fulfill important ecological functions, such as decomposing organic matter and releasing nutrients into the soil.

As symbionts of multicellular organisms, they perform useful functions for their host. On the other hand, some species are so-called opportunistic human pathogens: particularly in a weakened immune system, such fungi can colonize the body and cause serious and even life-threatening infections.

While fungi are often studied as pathogens of crops at institutions such as Kiel University and the Max Planck Institute for Evolutionary Biology in Plön (MPI-EvolBio), researchers are increasingly turning their attention to their harmful effects on humans. A research team led by Professor Eva Stukenbrock, head of the Environmental Genomics group at Kiel University and MPI-EvolBio, has conducted a new study to investigate why certain fungi might become human pathogens in the course of global change. To this end, the researchers analyzed various fungal species of the order Trichosporonales, which includes both harmless and dangerous species for humans.

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