Lifeboat Foundation

Advanced age is a shared risk factor for many chronic and debilitating skeletal diseases including osteoporosis and periodontitis. Mesenchymal stem cells develop various aging phenotypes including the onset of senescence, intrinsic loss of regenerative potential and exacerbation of inflammatory microenvironment via secretory factors. This review elaborates on the emerging concepts on the molecular and epigenetic mechanisms of MSC senescence, such as the accumulation of oxidative stress, DNA damage and mitochondrial dysfunction. Senescent MSCs aggravate local inflammation, disrupt bone remodeling and bone-fat balance, thereby contributing to the progression of age-related bone diseases. Various rejuvenation strategies to target senescent MSCs could present a promising paradigm to restore skeletal aging.

Periodic prolonged fasting (PF) extends lifespan in model organisms and ameliorates multiple disease states both clinically and experimentally owing, in part, to its ability to modulate the immune system. However, the relationship between metabolic factors, immunity, and longevity during PF remains poorly characterized especially in humans.

This study aimed to observe the effects of PF in human subjects on the clinical and experimental markers of metabolic and immune health and uncover underlying plasma-borne factors that may be responsible for these effects.

In this rigorously controlled pilot study ( ClinicalTrial.gov identifier, NCT03487679), 20 young males and females participated in a 3D study protocol including assessments of 4 distinct metabolic states: 1) overnight fasted baseline state, 2) 2-h postprandial fed state, 3) 36-h fasted state, and 4 ) final 2-h postprandial re-fed state 12 h after the 36-h fasting period. Clinical and experimental markers of immune and metabolic health were assessed for each state along with comprehensive metabolomic profiling of participant plasma. Bioactive metabolites identified to be upregulated in circulation after 36 h of fasting were then assessed for their ability to mimic the effects of fasting in isolated human macrophage as well as the ability to extend lifespan in Caenorhabditis elegans.

Nanomedicine uses nanomaterials [e.g., carbon nanotubes (CNTs), nanoparticles, and nanodiscs] or organic nanostructures (e.g., DNA origami and liposomes) for drug delivery (8–10), medical imaging (11–14), and tissue regeneration (15). Nanomaterials offer therapeutic efficacy through their tissue permeation, interaction with an external energy source, and capability to be combined with other therapeutic modalities (16, 17). Because we recently demonstrated that GBM cells are mechanosensitive (18), we set to use nanomaterials to develop a nanoscale mechanical approach to treat GBM. Mechanical perturbation has been investigated as an approach to target cancer cells. For example, magnetic field–actuated nanomaterials compromise the integrity of plasma membrane, leading to the death of in vitro–cultured GBM cells (19) and breast cancer cells (20). GBM cells, which were preincubated with magnetic nanoparticles, were implanted into mice to generate xenograft tumors. A rotating magnetic field, which was then applied to these magnetic particles–harboring tumors, suppressed GBM growth (21). Similarly, magnetic field mobilization of mitochondria-targeting magnetic nanoparticle chains demonstrated efficacy in inhibiting GBM growth in mice (22). While these studies showed that magnetic field–controlled nanomaterials can be used in cancer treatment, the utility of magnetic nanomaterials in treating chemoresistant tumors, the root cause of tumor relapse and patient death, remains unexplored.

GBM displays an extreme level of heterogeneity at genomic, epigenetic, biochemical signaling, and cellular composition levels (23). The heterogeneous nature of GBM confers treatment resilience to tumors and leads to a unifying therapy resistance mechanism; i.e., suppressing selected proteins or biochemical pathways provides a fertile ground for alternative signaling mechanisms, which are not targeted by the given therapy, to fuel GBM growth (24). In other words, the “whack-a-mole” approach failed to benefit patients with GBM for decades. For this reason, we hypothesized that nanomaterial-based mechanical treatment of cancer cells, rather than specific targeting of signaling pathways, can overcome the therapy resistance of this biologically plastic disease. To this end, we engineered a mechanical nanosurgery approach using magnetic CNTs (mCNTs; nanotubes with carbon surface and a cavity filled with iron particles) based on the following reasons.

Combining an optical tweezer technology called C-trap that manipulates a single molecule of DNA and a novel approach, researchers were able to receive a detailed view into how cells find and repair damaged DNA.

Their findings are described in an article titled, “Single-molecule analysis of DNA-binding proteins from nuclear extracts (SMADNE),” published in Nucleic Acids Research.

In the new study, the researchers used the C-trap to investigate how different DNA repair proteins identify and bind to their respective forms of damage.

Assessing how energy-generating synthetic organelles could sustain artificial cells.

Researchers have assessed the progress and challenges in creating artificial mitochondria and chloroplasts for energy production in synthetic cells. These artificial organelles could potentially enable the development of new organisms or biomaterials. The researchers identified proteins as the most crucial components for molecular rotary machinery, proton transport, and ATP production, which serves as the cell’s primary energy currency.

Energy production in nature is the responsibility of chloroplasts and mitochondria and is crucial for fabricating sustainable, synthetic cells in the lab. Mitochondria are not only “the powerhouses of the cell,” as the middle school biology adage goes, but also one of the most complex intracellular components to replicate artificially.

CRISPR Is The Future.

Welcome to the future!

It is the year 2050, and the world is facing a crisis. Climate change has caused widespread devastation, and the planet’s resources are dwindling. Famine and disease are rampant, and humanity is on the brink of collapse. But amidst the chaos, a new hope emerges.

O.o!!!

A fungal superbug called Candida auris is spreading rapidly through hospitals and nursing homes in the US. The first case was identified in 2016. Since then, it has spread to half the country’s 50 states. And, according to a new report, infections tripled between 2019 and 2021.

This is hugely concerning because Candida auris is resistant to many drugs, making this fungal infection one of the hardest to treat.

Continue reading “New Deadly Superfungus Can Now Be Found in Half of US States” »

A team of scientists at the Sloan Kettering Institute have identified the STING cellular signaling pathway as a key player in keeping dormant cancer cells from progressing into aggressive tumors months, or even years, after they’ve escaped from a primary tumor.

The findings, which were published in Nature on March 29, suggest that drugs to activate STING could help prevent the spread of cancer to new sites throughout the body—a process known as metastasis.

In mouse models of lung cancer, treatment that stimulated the STING pathway helped eliminate lingering cancer cells and prevent them from progressing to aggressive metastases. Known as micrometastases, these cells, which can be found individually and in small clusters, are too small to be detected with standard imaging tests.

The hNSCs used in the study have been produced and characterised in the Cell Factory and Biobank of Santa Maria Hospital (Terni, Italy), authorised by the Italian Medicine Agency (AIFA) for the production of hNSCs to be used for clinical trials (aM 54/2018). The methodology applied to isolate, expand, characterise and cryopreserve the lines is based on the Neurosphere Assay^26,41,54, and has been used for the production of the cells utilised in phase I trials for Amyotrophic Lateral Sclerosis patients (NCT01640067²³) and for Secondary Progressive Multiple Sclerosis patients (NCT03282760, ongoing).

The entire production process, starting from tissue procurement to cryopreservation is compliant to cGMP guidelines and approved by AIFA. The hNSCs are obtained from foetal brain tissue derived from fetuses that underwent miscarriage or natural in utero death upon receiving the signed informed consent from the mother. Forty-eight hours prior to implantation, hNSCs were plated in the growth medium at a concentration of 10,000 cells/cm². On the day of surgery, hNSCs were collected by centrifugation, viable cells were counted by Trypan blue exclusion criteria, and the correct number of cells were re-suspended in HBSS for the transplant.

SOD1 transgenic male rats were randomly divided into three experimental groups: (i) transplanted with hNSCs (hNSC rats, n = 15); (ii) treated with HBSS (HBSS rats, n = 15) and (iii) untreated (CTRL rats, n = 22). An additional group of non-transgenic littermates (wild-type, WT, n = 9) were used as controls for symptomatic evaluation of the colony. Tacrolimus (FK506) and cyclosporine (cyclosporin A) are the principal immunosuppressive drugs that have been applied for solid organ transplantation^55,56 and have been translated to stem cell treatments for PD⁵⁷ and ALS²². In animal models, despite differences in potency, both drugs showed excellent survival rates for grafts across many comparative studies^58,59. Our previous results^44,45 showed that hNSCs can survive—without signs of rejection—in the rat brain up to 6 months under transient immunosuppression treatment, with cyclosporin A. On the bases of these results, we applied the same immunosuppressive treatment with administration of cyclosporine A (15 mg/kg/day subcutaneous; Sandimmne, Novartis) that was initiated on the day of transplantation and continued for 15 days after surgery (for all animal groups).