Polo-like kinase 1 (Plk1) is a master regulator of mitosis, initiating key steps of cell cycle regulation, and its overexpression is associated with certain types of cancer. In this study, the authors carefully designed peptides that were able to bind to Plk1 at a location that is important for its proper localization and function. Future studies could further develop these peptides to selectively target Plk1 in cancer cells and induce mitotic arrest.
In this study, the authors identify new potential targets to treat advanced diffuse large B-cell lymphoma after treatment relapse and loss of CD19 expression.
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 the United States, there are currently 17.8 million affected by atopic dermatitis (AD), commonly known as eczema. It is characterized by itching and skin inflammation. AD patients are at higher risk for infections, depression, cancer, and suicide. Genetics, environment, and stress are some of the causes of the disease. With the rise of personalized medicine and the acceptance of gene-editing technologies, AD-related variations need to be identified for treatment. Genome-wide association studies (GWAS) have associated the Filaggrin (FLG) gene with AD but have not identified specific problematic single nucleotide polymorphisms (SNPs). This research aimed to refine known SNPs of FLG for gene editing technologies to establish a causal link between specific SNPs and the diseases and to target the polymorphisms. The research utilized R and its Bioconductor packages to refine data from the National Center for Biotechnology Information's (NCBI's) Variation Viewer. The algorithm filtered the dataset by coding regions and conserved domains. The algorithm also removed synonymous variations and treated non-synonymous, frameshift, and nonsense separately. The non-synonymous variations were refined and ordered by the BLOSUM62 substitution matrix. Overall, the analysis removed 96.65% of data, which was redundant or not the focus of the research and ordered the remaining relevant data by impact. The code for the project can also be repurposed as a tool for other diseases. The research can help solve GWAS's imprecise identification challenge. This research is the first step in providing the refined databases required for gene-editing treatment.
Uveal melanoma (UM) is a rare subtype of melanoma but the most frequent primary cancer of the eye in adults. The goal of this study was to research the genetic causes of UM through a comprehensive frequency analysis of base-pair mismatches in patient genomes. Results showed a total of 130 genetic mutations, including seven recurrent mutations, with most mutations occurring in chromosomes 3 and X. Recurrent mutations varied from 8.7% to 17.39% occurrence in the UM patient sample, with all mutations identified as missense. These findings suggest that UM is a recessive heterogeneous disease with selective homozygous mutations. Notably, this study has potential wider significance because the seven genes targeted by recurrent mutations are also involved in other cancers.
Dhar and colleagues established a Type II diabetes mellitus (T2DM) model in fruit flies, using this model to induce insulin resistance and characterize the effects Resveratrol and Pterostilbene on a number of growth and activity metrics. Resveratrol and Pterostilbene treatment notably overturned the weight gain and glucose levels. The results of this study suggest that Drosophila can be utilized as a model organism to study T2DM and novel pharmacological treatments.
Resveratrol is a type of stillbenoid, a phenolic compound produced in plants, that is known for its anti-inflammatory and anticancer effects. Many oligomers of resveratrol have recently been isolated their bioactivities remain unknown. Here, authors compared the bioactivities of resveratrol with natural dimers (ε-viniferin and gnetin H) and trimers (suffruticosol B and C). Results provide preliminary evidence that resveratrol oligomers could be potential preventive or therapeutic agents for cancers and other immune-related diseases
We systematically evaluated the effects of raw material composition, heat treatment, and mechanical properties on 13-8PH stainless steel alloy. The results of the neural network models were in agreement with experimental results and aided in the evaluation of the effects of aging temperature on double shear strength. The data suggests that this model can be used to determine the appropriate 13-8PH alloy aging temperature needed to achieve the desired mechanical properties, eliminating the need for many costly trials and errors through re-heat treatments.
Tertiary lymphoid structures (TLS) are lymph node-like structures that form at sites of inflammation, and their presence in cancer patients is predictive of a better clinical outcome. One significant obstacle to TLS formation is reduced immune cell infiltration into the tumor microenvironment (TME). Recent studies have shown that vasculature normalizing (VN) agents may override this defect to improve tissue perfusion and increased immune cell entry into the TME. However, their effects on immune cell and tumor cell phenotype remain understudied. Here the authors investigate whether treating tumor cells with VN would reduce their immunosuppressive phenotype and promote production of chemokine that recruit immune cells and foster TLS formation.
Plastic debris can disrupt marine ecosystems, spread contaminants, and take years to naturally degrade. In this study, Wu et al aim to establish an understanding of the scope of Williamston, Michigan’s microplastics problem, as well as to attempt to find the source of these plastics. Initially, the authors hypothesize that the Williamston Wastewater Treatment Plant was the primary contributor to Williamston’s microplastics pollution. Although they find a general trend of increasing concentrations of microplastics from upstream to downstream, they do not pinpoint the source of Williamston’s microplastics pollution in the present research.