Targeting mitochondrial metabolism by the mitotoxin bromoxib in leukemia and lymphoma cells.

Targeting mitochondrial metabolism represents a promising approach for cancer treatment. Here, we investigated the mitotoxic potential of the polybrominated diphenyl ether bromoxib, a natural compound isolated from the marine sponge Dysidea family. We could show that bromoxib comprised strong cytotoxicity in different leukemia and lymphoma cell lines (such as HL60, HPBALL, Jurkat, K562, KOPTK1, MOLT4, SUPB15 and Ramos), but also in solid tumor cell lines (such as glioblastoma cell lines SJ-GBM2 and TP365MG).

Co-targeting HSP90 alpha and CDK7 overcomes resistance against HSP90 inhibitors in BCR-ABL1+ leukemia cells.

HSP90 has emerged as an appealing anti-cancer target. However, HSP90 inhibitors (HSP90i) are characterized by limited clinical utility, primarily due to the resistance acquisition via heat shock response (HSR) induction. Understanding the roles of abundantly expressed cytosolic HSP90 isoforms (α and β) in sustaining malignant cells' growth and the mechanisms of resistance to HSP90i is crucial for exploiting their clinical potential.

The Golgi stacking protein GRASP55 is targeted by the natural compound prodigiosin.

Background: The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it has been reported to affect cancer cells but not non-malignant cells, rendering prodigiosin a promising lead compound for anticancer drug discovery. However, a direct protein target has not yet been experimentally identified.

Milmed Yeast Alters the LPS-Induced M1 Microglia Cells to Form M2 Anti-Inflammatory Phenotype.

Microglial cells polarized towards a proinflammatory phenotype are considered the main cellular players of neuroinflammation, underlying several neurodegenerative diseases. Many studies have suggested that imbalance of the gut microbial composition is associated with an increase in the pro-inflammatory cytokines and oxidative stress that underlie chronic neuroinflammatory diseases, and perturbations to the gut microbiota were detected in neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease. The importance of gut-brain axis has been uncovered and the relevance of an appropriate microbiota balance has been highlighted.

Solid-Phase Synthesis of Cereblon-Recruiting Selective Histone Deacetylase 6 Degraders (HDAC6 PROTACs) with Antileukemic Activity.

In this work, we utilized the proteolysis targeting chimera (PROTAC) technology to achieve the chemical knock-down of histone deacetylase 6 (HDAC6). Two series of cereblon-recruiting PROTACs were synthesized via a solid-phase parallel synthesis approach, which allowed the rapid preparation of two HDAC6 degrader mini libraries. The PROTACs were either based on an unselective vorinostat-like HDAC ligand or derived from a selective HDAC6 inhibitor.

The mycotoxin viriditoxin induces leukemia- and lymphoma-specific apoptosis by targeting mitochondrial metabolism.

Inhibition of the mitochondrial metabolism offers a promising therapeutic approach for the treatment of cancer. Here, we identify the mycotoxin viriditoxin (VDT), derived from the endophytic fungus Cladosporium cladosporioides, as an interesting candidate for leukemia and lymphoma treatment. VDT displayed a high cytotoxic potential and rapid kinetics of caspase activation in Jurkat leukemia and Ramos lymphoma cells in contrast to solid tumor cells that were affected to a much lesser extent.

mall olecule ranged hermal roximity oggregation (smarTPCA)-A Novel Approach to Characterize Protein-Protein Interactions in Living Cells by Similar Isothermal Dose-Responses.

Chemical biology and the application of small molecules has proven to be a potent perturbation strategy, especially for the functional elucidation of proteins, their networks, and regulators. In recent years, the cellular thermal shift assay (CETSA) and its proteome-wide extension, thermal proteome profiling (TPP), have proven to be effective tools for identifying interactions of small molecules with their target proteins, as well as off-targets in living cells. Here, we asked the question whether isothermal dose-response (ITDR) CETSA can be exploited to characterize secondary effects downstream of the primary binding event, such as changes in post-translational modifications or protein-protein interactions (PPI).

The signal transducer CD24 suppresses the germ cell program and promotes an ectodermal rather than mesodermal cell fate in embryonal carcinomas.

Testicular germ cell tumors (GCTs) are stratified into seminomas and nonseminomas. Seminomas share many histological and molecular features with primordial germ cells, whereas the nonseminoma stem cell population-embryonal carcinoma (EC)-is pluripotent and thus able to differentiate into cells of all three germ layers (teratomas). Furthermore, ECs are capable of differentiating into extra-embryonic lineages (yolk sac tumors, choriocarcinomas).

Why flipping the classroom is not enough: Digital curriculum making after the pandemic.

To slow down the proliferation of Covid-19, governments virtually shut down public life, temporarily closed schools, and forced teaching to be done exclusively on a remote basis. These measures offer an opportunity to reexamine conventional teaching and learning arrangements, test new digital and analogue concepts, and provide essential inspiration for curriculum making in the twenty-first century. This article addresses the historical development of schooling in the classroom as differentiated from "homeschooling".

Comparative Secretomics Gives Access to High Confident Secretome Data: Evaluation of Different Methods for the Determination of Bona Fide Secreted Proteins.

Secretome analysis is broadly applied to understand the interplay between cells and their microenvironment. In particular, the unbiased analysis by mass spectrometry-based proteomics of conditioned medium has been successfully applied. In this context, several approaches have been developed allowing to distinguish proteins actively secreted by cells from proteins derived from culture medium or proteins released from dying cells.

Laying an Early Foundation: Lifestyle Medicine Pre-Professional Education (LMPP) Member Interest Group.

Just as lifestyle medicine is the necessary foundation for true health care reform, lifestyle medicine competencies should be the foundation for health education. Although lifestyle medicine education may benefit a health professional at any stage in their education or career, evidence-based undergraduate lifestyle medicine education for future health professionals shifts the perspective of health and health care delivery. Educating health preprofessionals in associate, bachelor's, master's, and other preprofessional healthcare training programs is of paramount importance due to the interdisciplinary nature of lifestyle medicine.

Using the SMART-EST Goals in Lifestyle Medicine Prescription.

Lifestyle modifications can effectively decrease chronic disease risk but studies show little to no time during patient encounters is spent on lifestyle medicine counseling. The SMART-EST goal framework facilitates both a rich discussion of lifestyle medicine and a comprehensive patient-centered action plan for health behavior change. The tenets of the SMART-EST goal-setting process are discussed.

Solution-processed transparent ferroelectric nylon thin films.

Ferroelectricity, a bistable ordering of electrical dipoles in a material, is widely used in sensors, actuators, nonlinear optics, and data storage. Traditional ferroelectrics are ceramic based. Ferroelectric polymers are inexpensive lead-free materials that offer unique features such as the freedom of design enabled by chemistry, the facile solution-based low-temperature processing, and mechanical flexibility.

Depolarization of multidomain ferroelectric materials.

Depolarization in ferroelectric materials has been studied since the 1970s, albeit quasi-statically. The dynamics are described by the empirical Merz law, which gives the polarization switching time as a function of electric field, normalized to the so-called activation field. The Merz law has been used for decades; its origin as domain-wall depinning has recently been corroborated by molecular dynamics simulations.

Long-Term Outcomes of a Cardiovascular and Diabetes Risk-Reduction Program Initiated by a Self-Insured Employer.

Background: Cardiovascular disease remains the leading cause of death in America and poses a significant challenge for self-insured employers attempting to improve employee health and well-being while controlling healthcare costs. Disease state management programs can be an effective means of achieving these outcomes, but the durability and long-term effects of such programs have limited evaluation.

Objective: To assess the 5-year health, economic, and quality-of-life patient outcomes of an employer-sponsored disease state management program.

Quantum tunnelling and charge accumulation in organic ferroelectric memory diodes.

Non-volatile memories-providing the information storage functionality-are crucial circuit components. Solution-processed organic ferroelectric memory diodes are the non-volatile memory candidate for flexible electronics, as witnessed by the industrial demonstration of a 1 kbit reconfigurable memory fabricated on a plastic foil. Further progress, however, is limited owing to the lack of understanding of the device physics, which is required for the technological implementation of high-density arrays.

The negative piezoelectric effect of the ferroelectric polymer poly(vinylidene fluoride).

Piezoelectricity describes interconversion between electrical charge and mechanical strain. As expected for lattice ions displaced in an electric field, the proportionality constant is positive for all piezoelectric materials. The exceptions are poly(vinylidene fluoride) (PVDF) and its copolymers with trifluoroethylene (P(VDF-TrFE)), which exhibit a negative longitudinal piezoelectric coefficient.

Using S-adenosyl-L-homocysteine capture compounds to characterize S-adenosyl-L-methionine and S-adenosyl-L-homocysteine binding proteins.

S-Adenosyl-l-methionine (SAM) is recognized as an important cofactor in a variety of biochemical reactions. As more proteins and pathways that require SAM are discovered, it is important to establish a method to quickly identify and characterize SAM binding proteins. The affinity of S-adenosyl-l-homocysteine (SAH) for SAM binding proteins was used to design two SAH-derived capture compounds (CCs).

Tool guide for lifestyle behavior change in a cardiovascular risk reduction program.

Lifestyle medicine behaviors such as a healthy diet, physical activity, and tobacco avoidance, are the cornerstone of treatment in many chronic disease conditions, especially those related to the cardiovascular system. In fact, 80% of premature heart disease, stroke, and diabetes may be prevented through modification of these behaviors. The rate-limiting step in cardiovascular disease prevention is the implementation and maintenance of healthy lifestyle behaviors.

Comparison of cardiovascular risk calculation tools in pharmacy practice.

Objective: To examine the use of various cardiovascular disease (CVD) risk estimation calculators in pharmacy practice.

Design: Longitudinal cohort study.

Setting: Midwestern university worksite from August 2008 through May 2012.

Phosphonate- and carboxylate-based self-assembled monolayers for organic devices: a theoretical study of surface binding on aluminum oxide with experimental support.

We report a computational study on the chemical bonding of phosphonates and carboxylates to aluminum oxide surfaces and how the binding properties are related to the amount of water in the experimental environment. Two different surface structures were used in the calculations in order to model representative adsorption sites for the phosphonates and carboxylates and to account for the amorphous nature of the hydroxylated AlOx films in experiment. For the phosphonates, we find that the thermodynamically preferred binding mode changes between mono-, bi-, and tridentate depending on the surface structure and the amount of residual water.

Reducing the risk of obesity: defining the role of weight loss drugs.

The prevalence of obesity has increased dramatically in the past 20 years. As a public health concern, obesity is associated with a health care resource burden that is quickly approaching that associated with tobacco use. Although lifestyle intervention (diet and exercise) remains the mainstay of treatment of obesity, its effectiveness is limited by poor long-term adherence.

Development of a Composite Lifestyle Index and Its Relationship to Quality of Life Improvement: The CLI Pilot Study.

An important component to optimal health is quality of life (QOL). Several healthy lifestyle behaviors have independently shown to improve QOL. The simultaneous implementation of multiple lifestyle behaviors is thought to be difficult, and the current literature lacks the assessment of multiple lifestyle behaviors simultaneously with respect to the effect on QOL.

Self-assembled monolayer exchange reactions as a tool for channel interface engineering in low-voltage organic thin-film transistors.

In this work, we compared the kinetics of monolayer self-assembly long-chained carboxylic acids and phosphonic acids on thin aluminum oxide surfaces and investigated their dielectric properties in capacitors and low-voltage organic thin-film transistors. Phosphonic acid anchor groups tend to substitute carboxylic acid molecules on aluminum oxide surfaces and thus allow the formation of mixed or fully exchanged monolayers. With different alkyl chain substituents (n-alkyl or fluorinated alkyl chains), the exchange reaction can be monitored as a function of time by static contact angle measurements.