Kalirin is a guanine nucleotide exchange factor (GEF) for the GTPase RAC1, linked to schizophrenia and Alzheimer’s Disease. It plays a crucial role in synaptic plasticity by regulating dendritic spine formation and actin cytoskeleton remodeling, which are essential for creating new synapses. Authors developed two novel compounds targeting kalirin, confirming that predictive modeling can indicate biological activity.
The authors looked at the effects of commonly used anesthetics in rodents on brain activity (specifically quasi-periodic patterns). Understanding effects on brain activity is important for researchers to understand when choosing rodent models for disease.
According to the World Health Organization, cancer is a leading cause of death globally. The disease’s prevalence is rapidly increasing in association with factors including the increased use of pesticides and herbicides, such as glyphosate, which is one of the most widely used herbicide ingredients. Natural antioxidants and phytochemicals are being tested as anti-cancer agents due to their antiproliferative, antioxidative, and pro-apoptotic properties. Thus, we aimed to investigate the potential role of S. amara extract as a therapeutic agent against glyphosate-induced toxicity and tumor-like morphologies in regenerating and homeostatic planaria (Dugesia dorotocephala).
Many common respiratory illnesses like bronchitis, asthma, and chronic obstructive pulmonary disease (COPD) lead to bronchial inflammation and, subsequently, a blockage. However, there are many difficulties in measuring the severity of the blockage. A numeric metric to determine the degree of the blockage severity is necessary. To tackle this demand, we aimed to develop a novel human respiratory model and design a deep-learning program that can constantly monitor and report bronchial blockage by recording breath sounds in a non-intrusive way.
PDE8, a type of phosphodiesterase (PDE), is proven to be crucial in various cellular activities and physiological activities by influencing second messenger systems. It is involved in a wide range of diseases, including Alzheimer’s disease and various heart diseases. However, there is limited information about PDE8 selective inhibitors. This work aimed to improve the solubility and yield of PDE8 in the supernatant by exploring suitable culture conditions, including temperatures and different additives.
Glioblastoma Multiforme (GBM) is the most malignant brain tumor with the highest fraction of genome alterations (FGA), manifesting poor disease-free status (DFS) and overall survival (OS). We explored The Cancer Genome Atlas (TCGA) and cBioportal public dataset- Firehose legacy GBM to study DNA repair genes Activating Signal Cointegrator 1 Complex Subunit 3 (ASCC3) and Alpha-Ketoglutarate-Dependent Dioxygenase AlkB Homolog 3 (ALKBH3). To test our hypothesis that these genes have correlations with FGA and can better determine prognosis and survival, we sorted the dataset to arrive at 254 patients. Analyzing using RStudio, both ASCC3 and ALKBH3 demonstrated hypomethylation in 82.3% and 61.8% of patients, respectively. Interestingly, low mRNA expression was observed in both these genes. We further conducted correlation tests between both methylation and mRNA expression of these genes with FGA. ASCC3 was found to be negatively correlated, while ALKBH3 was found to be positively correlated, potentially indicating contrasting dysregulation of these two genes. Prognostic analysis showed the following: ASCC3 hypomethylation is significant with DFS and high ASCC3 mRNA expression to be significant with OS, demonstrating ASCC3’s potential as disease prediction marker.
As cancer continues to take millions of lives worldwide, the need to create effective therapeutics for the disease persists. The kinesin Eg5 assembly motor protein is a promising target for cancer therapeutics as inhibition of this protein leads to cell cycle arrest. Monastrol, a small dihydropyrimidine-based molecule capable of inhibiting the kinesin Eg5 function, has attracted the attention of medicinal chemists with its potency, affinity, and specificity to the highly targeted loop5/α2/α3 allosteric binding pocket. In this work, we employed high-throughput virtual screening (HTVS) to identify potential small molecule Eg5 inhibitors from a designed set of novel dihydropyrimidine analogs structurally similar to monastrol.
In this study, the authors observe if the symptoms of Rett Syndrome, a neurodegenerative disease in humans, are reflected in Drosophila melanogaster. This was achieved by differentiating the behavior and physical aspects of wild-type flies from flies expressing the full-length MeCP2 gene and the mutated MeCP2 gene (R106W). After conducting these experiments, some of the Rett Syndrome symptoms were recapitulated in Drosophila, and a subset of those were partially ameliorated by the introduction of pifithrin-alpha.
Cardiac autonomic and structural changes may occur in temporal lobe epilepsy patients and contribute to the risk of sudden unexpected death in epilepsy patients. Choi and colleagues reviewed clinical charts to obtain patients’ lifetime seizure count, antiepileptic drug use, and history of heart disease, followed by transthoracic echocardiogram to calculate left ventricle dimensions, ejection fraction, and left ventricle mass. By comparing epilepsy patients to control subjects, they found that epilepsy patients had thinner left ventricle walls and smaller ejection fraction, but with no significant difference in left ventricle mass.
Patel et al. explore whether T. paniculatum plant extract can work with modern antibiotics to increase antibiotic efficacy against common disease-causing bacteria. The plant extract in conjunction with the antibiotic shows promise in battling S. aureus. The authors present a cost-effective method to increase antibiotic efficacy in a time where antibiotic resistant bacteria is becoming a growing problem.