Adlerhaaning0479
Of these, 5 novel microRNAs were reported for the first time to be associated with RPL. These comprised Hsa-let-7e, Hsa-miR-519d, Hsa-miR-410 which were upregulated, and Hsa-let-7a, Hsa-let-7d which were downregulated in RPL. While its association with RPL was reported earlier, this study is also the first to report on the upregulation of Hsa-miR-184 in circulating fluids in association with RPL. The study provides for understanding circulating microRNAs expression pattern in RPL which may be involved in its pathogenesis and demonstrates their potential role as noninvasive diagnostic and prognostic biomarkers for RPL.Early reports suggest that lockdown measures associated with the COVID-19 pandemic (e.g., social distancing) are having adverse consequences for people's mental health, including increases in maladaptive eating habits and body dissatisfaction. Certain groups, such as those with pre-existing mental health difficulties, may be especially at risk. The current study explored perceived changes in eating, exercise, and body image during lockdown within the United Kingdom, using an online survey (n = 264). There were large individual differences in perceived changes in eating, exercise, and body image in this period. Women were more likely than men to report increasing struggles with regulating eating, preoccupation with food and worsening body image. Those with a current/past diagnosis of eating disorders reported significantly greater difficulties in regulating eating, increased preoccupation with food, exercise thoughts and behaviours and concern about appearance, even when compared to those with other mental health and developmental disorders. Ongoing research to explore individual differences in the trajectories of change in eating, exercise and body image as lockdown measures ease will be important for understanding the full psychological impact of this pandemic and improve service and public health planning going forward.We compare consumers' attitude towards and willingness to pay (WTP) for gene-edited (GE) apples in Europe and the US. Using hypothetical choices in a lab and different technology messages, we estimate WTP of 162 French and 166 US consumers for new apples, which do not brown upon being sliced or cut. Messages center on (i) the social and private benefits of having the new apples, and (ii) possible technologies leading to this new benefit (conventional hybrids, GE, and genetically modified (GMO)). French consumers do not value the innovation and actually discount it when it is generated via biotechnology. US consumers do value the innovation as long as it is not generated by biotechnology. In both countries, the steepest discount is for GMO apples, followed by GE apples. Furthermore, the discounting occurs through "boycott" consumers who dislike biotechnology. However, the discounting is weaker for US consumers compared to French consumers. Favorable attitudes towards sciences and new technology totally offset the discounting of GE apples.
The p53, tumor suppressor protein is inactivated upon mutation in the DNA-binding domain and the non-functional protein leads to cancers. Inderal The p53Y220C is one of the most frequently observed mutations in p53 with a scope of rescuing the protein function using small molecules.
Using computational modeling, biophysical, and experimental cell-based studies we tried to understand the molecular basis of Curcumin as a potential small molecule to stabilize p53Y220C mutant and restore its function. The pancreatic adenocarcinomas BxPC-3 p53Y220C mutant cell line was used for cell-based assays to determine the therapeutic potential of Curcumin to restore mutant p53 to function like wild type.
Our results showed that the Curcumin binds p53Y220C with K
=3.169±0.257μM and it increases the DNA binding affinity of the mutant by 4-fold with K
=851.29±186.27nM. By Fluorescence, CD, and IR spectroscopy, we could characterize the secondary structural changes and stabilization of the p53Y220C DNA binding domain upon Curcumin binding. By caspase-3 and Annexin V assays, we could demonstrate that Curcumin at 3μM to 8μM concentration could initiate p53 mediated apoptosis in BxPC-3 cell line. Based on our experimental studies, we propose a mechanism for the activation of ATM/Chk1 kinases pathways for apoptosis and/or G2/M cell cycle arrest in the BxPC-3 cell line mediated by functionally restored p53Y220C.
The study indicated that the natural compound Curcumin could rescue mutant p53Y220C in BxPC-3 pancreatic adenocarcinomas cell line to function like wild-type and activate apoptotic pathways.
The study indicated that the natural compound Curcumin could rescue mutant p53Y220C in BxPC-3 pancreatic adenocarcinomas cell line to function like wild-type and activate apoptotic pathways.
Carbon nanotubes (CNTs) show great promise as theranostic agents due to their drug delivery properties, intrinsic near-infrared radiation-responsiveness, and magnetic functionalization. However, temperature elevation caused by these external stimuli during drug delivery should be considered for the evaluation of CNT-based systems loaded with temperature-sensitive biomolecules.
We examine the thermal stability of a 33 nucleotides long hairpin miRNA encapsulated in (20,20) CNT using all-atom molecular dynamics simulations in explicit water. We systematically increase the temperature as 298, 310, 327, and 343K, reaching the melting temperature of miRNA. To emphasize the effect of the aromatic confined space, we compare the dynamics of miRNA inside the CNT to its dynamics free in the solution at the same temperatures, reaching a total simulation time of 7.9μs.
miRNA hairpin mostly maintains its double-stranded structure in the confined CNT, even at elevated temperatures. Binding free energies and potential of mean force calculations also underline the strong π-π interactions between the biomolecule and the CNT for 298-343K.
The let-7 miRNA mimic, which represents a wide family of RNAi-based therapeutics, can be transported in the CNT under medically applied hyperthermic conditions.
This study shows how the structure and dynamics of miRNA hairpin are affected when encapsulated in an aromatic tube, during a systematic increase of temperature. It also indicates the high potential of CNT-based systems for the delivery of oligonucleotide therapeutics while simultaneous imaging/magnetic field guiding to the target tissue is achieved.
This study shows how the structure and dynamics of miRNA hairpin are affected when encapsulated in an aromatic tube, during a systematic increase of temperature. It also indicates the high potential of CNT-based systems for the delivery of oligonucleotide therapeutics while simultaneous imaging/magnetic field guiding to the target tissue is achieved.