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Category: biotech/medical – Page 1,023

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.

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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.

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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.

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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.

Candida auris is a yeast-type fungus that is the first to have multiple international health alerts associated with it. It has been found in over 30 countries, including the UK, since it was first identified in Japan in 2009.

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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 , are too small to be detected with standard imaging tests.

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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 Assay26,41,54, 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 transplantation55,56 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 studies58,59. Our previous results44,45 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).

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Huntington’s disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin (HTT) gene. The resulting polyglutamine (polyQ) tract alters the function of the HTT protein. Although HTT is expressed in different tissues, the medium spiny projection neurons (MSNs) in the striatum are particularly vulnerable in HD. Thus, we sought to define the proteome of human HD patient–derived MSNs. We differentiated HD72 induced pluripotent stem cells and isogenic controls into MSNs and carried out quantitative proteomic analysis. Using data-dependent acquisitions with FAIMS for label-free quantification on the Orbitrap Lumos mass spectrometer, we identified 6,323 proteins with at least two unique peptides. Of these, 901 proteins were altered significantly more in the HD72-MSNs than in isogenic controls. Functional enrichment analysis of upregulated proteins demonstrated extracellular matrix and DNA signaling (DNA replication pathway, double-strand break repair, G1/S transition) with the highest significance. Conversely, processes associated with the downregulated proteins included neurogenesis-axogenesis, the brain-derived neurotrophic factor-signaling pathway, Ephrin-A: EphA pathway, regulation of synaptic plasticity, triglyceride homeostasis cholesterol, plasmid lipoprotein particle immune response, interferon-γ signaling, immune system major histocompatibility complex, lipid metabolism and cellular response to stimulus. Moreover, proteins involved in the formation and maintenance of axons, dendrites, and synapses (e.g., Septin protein members) were dysregulated in HD72-MSNs. Importantly, lipid metabolism pathways were altered, and using quantitative image, we found analysis that lipid droplets accumulated in the HD72-MSN, suggesting a deficit in the turnover of lipids possibly through lipophagy. Our proteomics analysis of HD72-MSNs identified relevant pathways that are altered in MSNs and confirm current and new therapeutic targets for HD.

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Improving the seasonal influenza vaccine and public health specialists’ ability to predict pandemic potential in new flu strains may be possible, due to new findings from scientists at St. Jude Children’s Research Hospital. The key is the stability of a viral protein that gains entry into human cells. The findings were published today in Science Advances.

“We found that the protein flu viruses use to enter cells, hemagglutinin, needs to be relatively stable and resistant to acid in an effective H3N2 flu vaccine,” said senior and co-corresponding author Charles Russell, Ph.D., St. Jude Department of Infectious Diseases. “We found a mutation in hemagglutinin that makes the grow better in eggs also causes a mismatch in the vaccine. The mutation makes the virus unstable and makes it look less human-like.”

The H3N2 virus is a subtype of Influenza A and is one of the culprits behind the seasonal flu. Many flu vaccines are made by growing the virus in chicken eggs, but the virus can gain mutations during that process. Some of those changes, like the one uncovered by the St. Jude group, make the vaccine less effective in generating the ideal immune response. At the same time, other mutations have more beneficial impacts.

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