Small-interfering RNA olpasiran reduced lipoprotein(a)–apolipoprotein B particles by 95% with minimal rise in non–Lp(a)-apoB, lowering total apoB concentration in patients with cardiovascular disease.
This secondary analysis of the OCEAN(a)-DOSE randomized clinical trial investigates the effect of the small-interfering RNA olpasiran on atherogenic lipoproteins.
This retrospective cohort study reported an association between GLP1RA use and a lower risk of acute asthma exacerbations in adolescents with overweight or obesity, suggesting a potential dual benefit for this population.
This cohort study investigates the association between glucagonlike peptide-1 receptor agonist use and the risk of acute asthma exacerbations among adolescents with overweight or obesity and asthma.
We present the first comprehensive data set for the aluminium content of brain tissue in donors without a diagnosis of neurodegenerative disease. All donors fulfilled recently revised criteria for control brain tissues14. Approximately 80% of measured tissues have an aluminium content below 1.0 μg/g dry wt. (Table 1). There are some anomalies, 6 out of 191 tissues have an aluminium content ≥3.00 μg/g dry wt., and these are worth future investigation to identify possible neuropathology. There was no statistically significant relationship between brain aluminium content and age of donor and this observation is contrary to a previous investigation of brain aluminium in a neurologically normal population15. An explanation may be that herein only two out of twenty donors were below 66 years old. The data do support a conclusion that a high content of brain aluminium is not an inevitability of ageing.
When we compared the new control data set with data produced in an identical manner in donors dying with diagnoses of sporadic Alzheimer’s disease (sAD)16, familial Alzheimer’s disease (fAD)11, autism spectrum disorder (ASD)13 and multiple sclerosis (MS)12 all of these disease groups had significantly higher brain aluminium content. The differences were always highly significant regardless of the method of statistical analysis (Table 4). The largest disease group, designated as sAD, was actually composed of approximately equal numbers of donors previously described by a brain bank as controls and donors diagnosed with sAD. Unfortunately, information discriminating between control and sAD donors was not made available to us17. However, the observation that the aluminium content of brain tissue in this group as a whole was significantly higher than the similarly aged control group emphasised the likelihood that brain aluminium content is increased in sAD.
Malignant tumors remain a primary cause of human mortality. Among the various treatment modalities for neoplasms, tumor vaccines have consistently shown efficacy and promising potential. These vaccines offer advantages such as specificity, safety, and tolerability, with mRNA vaccines representing promising platforms. By introducing exogenous mRNAs encoding antigens into somatic cells and subsequently synthesizing antigens through gene expression systems, mRNA vaccines can effectively induce immune responses. Katalin Karikó and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine for their great contributions to mRNA vaccine research. Compared with traditional tumor vaccines, mRNA vaccines have several advantages, including rapid preparation, reduced contamination, nonintegrability, and high biodegradability.
Imagine a container of tomatoes arriving at the container terminal in Aarhus. The papers state that the tomatoes are from Spain, but in reality, we have no way of knowing if that is true.
That is, unless we take a sample and have it analyzed in a laboratory, where scientists use DNA markers to determine whether the tomato is Spanish, South American or Chinese. This is both time-consuming and expensive.
But thanks to a scientific breakthrough, we will be able to examine tomatoes a lot quicker and cheaper, using special light producing proteins and our phones camera. Not right now, but in the near future.
The results were recently published in the journal Nature Communications.
“We have figured out how to instruct the proteins to generate light when specific DNA sequences appear. This could be used, as in the example with the tomatoes, but could also be useful in the healthcare sector, agriculture, or the pharmaceutical industry to analyze samples easily and cheaply,” the senior author explains.
The authors did this via “thiol switching”, using thiolated oligonucleotides: a protein is inactivated by conjugation to an oligonucleotide via a disulfide linkage; hybridization of the thiolated complementary oligonucleotide ensues disulfide exchange, the liberation of the enzyme, and the activation of enzymatic catalysis. In doing so, the researchers couple the most specific recognition event (hybridization) to the most effective tool of signal amplification (catalysis).
“Our primary goal is to control the activity of molecules in space and time, inside and outside of the cell. Specifically we focus on enzymes that can create ATP, which is the cell’s fuel, and polymerases, which the cell uses to build RNA and DNA.”
Children whose fathers took valproate within three months prior to conception were more likely to have neurodevelopmental disorders than children of men exposed to lamotrigine or levetiracetam.
Researchers behind a new study believe that it is the first to show an increased risk of neurodevelopmental disorders in offspring of fathers who took valproate rather than lamotrigine or levetiracetam prior to conceiving children.
Children whose fathers took valproate within the three months prior to their conception were more likely to have neurodevelopmental disorders, including autism spectrum disorders, than children of men exposed to lamotrigine or levetiracetam, according to a study published in JAMA Network Open in November.
The European research team—which analyzed medical records from Denmark, Norway, and Sweden—concluded that “health care practitioners should consider the potential risks associated with paternal valproate exposure and discuss alternative treatment options with male patients of reproductive age.” The team also said that “findings should be interpreted with caution due to the heterogeneity in the unadjusted estimates.”
Transposable elements in cancer therapy.
Transposable elements (TEs) are a major source of immunogenic nucleic acids that can be therapeutically reactivated in cancer cells to induce a state of viral mimicry.
TE expression can trigger innate immune sensing pathways, including type I interferon responses, and promote immunogenic cell death via sensors such as RIGI, MDA5, cGAS, and Z-DNA binding protein 1.
Although initially described in the context of epigenetic therapies, viral mimicry is now recognized as a shared response to diverse cancer treatment modalities, including chemotherapies and targeted therapies.
Despite their distinct primary mechanisms, these treatments converge on TE reactivation through disruption of DNA/histone methylation, p53 activation, and perturbation of mRNA splicing.
Therapeutic resistance to chemotherapy, radiation, and targeted agents is associated with TE silencing, identifying TE repression as a targetable axis of resistance.
Combination strategies to induce immunogenic TE expression can further enhance viral mimicry and boost antitumor immunity. https://sciencemission.com/Viral-mimicry-in-cancer-therapy
Scientists studying Alzheimer’s in African Americans have uncovered a striking genetic clue that may cut across racial lines. In brain tissue from more than 200 donors, the gene ADAMTS2 was significantly more active in people with Alzheimer’s than in those without it. Even more surprising, this same gene topped the list in an independent study of White individuals. The discovery hints at a common biological pathway behind Alzheimer’s and opens the door to new treatment strategies.