Unlocking Oxetane Potential: Modular Synthetic Platform for the Concise Synthesis of Acyclic Oligo-Isoprenoids and Terpenoids.

Terpenes occupy a unique place among the secondary metabolites due to their broad utility and extraordinary structural diversity. Their synthesis via polyene cyclization, either biomimetic or enzymatic, represents the cutting edge of modern synthetic chemistry. However, these endeavors have been inherently tied to the availability of natural and non-natural acyclic polyene starting materials.

One Step Back from Bedside to the Bench-How Do Different Arterial Stiffness Parameters Behave in Relation to Peripheral Resistance?

The investigation of arterial stiffening is a promising approach to estimating cardiovascular risk. Despite the widespread use of different methods, the dynamic nature of measured and calculated stiffness parameters is marginally investigated. We aimed to determine the stability of large artery elasticity parameters assessed via commonly used, ultrasound-based and oscillometric methods in relation to peripheral resistance modulation.

Development of a Standardized Bone Marrow Procedure Training and Competency Toolkit for Advanced Practice Providers in a Large Community Oncology Practice.

Bone marrow procedures are a common diagnostic tool utilized in hematology/oncology and can be completed in the office by trained clinicians. Currently, there are limited guidelines for appropriate training and competency for bone marrow procedures performed by advanced practice providers (APPs) in a community oncology practice setting. The need to create a standardized training and competency protocol for APPs in this setting was recognized.

Identifying the Leader in You.

The leadership journey is often a long and winding road, with speed bumps and unexpected turns. During this session of JADPRO Live Virtual, presenters discussed the leadership qualities that they have found integral, including emotional intelligence, vulnerability, and personal reflection.

Advanced Practitioner Leadership in Times of Crisis.

JADPRO Live Virtual kicked off with the opening panel on advanced practitioner leadership during the COVID-19 pandemic. The group discussed their institutional emergency protocols, how they leveraged advanced practitioners (APs) to provide care during the crisis peak, and how they responded to the personal issues and anxieties of their AP colleagues.

Telemedicine in Community Cancer Care: How Technology Helps Patients With Cancer Navigate a Pandemic.

COVID-19 places unprecedented demands on the oncology ecosystem. The extensive pressure of managing health care during the pandemic establishes the need for rapid implementation of telemedicine. Across our large statewide practice of 640 practitioners at 221 sites of service, an aggressive multidisciplinary telemedicine strategy was implemented in March by coordinating and training many different parts of our healthcare delivery system.

[Epigenetic effects affecting etoposide distribution and metabolism in the human body].

Etoposide is a topoisomerase II inhibitor antitumor agent which is widely used in the treatment of several hematologic malignancies and solid tumors. The therapeutic index of etoposide is quite high, thus its application causes several short-term and long-term side effects which can decrease the chance to cure patients. Drug dosing is based on body surface area calculation; recommendations for individual dosing do not exist yet.

Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA.

Recently, biological roles of extracellular vesicles (which include among others exosomes, microvesicles and apoptotic bodies) have attracted substantial attention in various fields of biomedicine. Here we investigated the impact of sustained exposure of cells to the fluoroquinolone antibiotic ciprofloxacin on the released extracellular vesicles. Ciprofloxacin is widely used in humans against bacterial infections as well as in cell cultures against Mycoplasma contamination.

Antiferromagnetically Coupled Dimeric Dodecacopper Supramolecular Architectures of Macrocyclic Ligands with a Symmetrical μ6-BO3(3-) Central Moiety.

Reactions between 2,6-diformyl-4-alkyl(R)-phenol (R = CH3 or C(CH3)3) and 1,3-diamino-2-hydroxypropane (1,3-DAP) in the presence of copper(II) salts (Cu(BF4)2·6H2O, Cu(ClO4)2·6H2O/H3BO3/Ar) and triethylamine (TEA) in a single pot result in self-assembly of dimeric dodecacopper supramolecular architectures of 30-membered hexatopic macrocyclic ligands (H6L4 and H6L5) with unique and fascinating structures having the BO3(3-) anion as the central species bonded to all six copper centers in a symmetrical fashion (μ6-BO3(3-)). A number of closely related macrocyclic hexacopper complexes are reported: {[Cu6(L4)(μ6-BO3)(μ-H2O)(C3H7NO)2(BF4)][BF4]2·3C3H7NO}2 (1) (DMF = C3H7NO), {[Cu6(L4)(μ6-BO3)(μ-C3H7NO)3][ClO4]3·3C3H7NO}2 (2), {[Cu6(L5)(μ6-BO3)(μ-OH)(H2O)3(C3H7NO)][BF4]2·6C3H7NO·4C2H5OH·2H2O}2 (3), {[Cu6(L5)(μ6-BO3)(μ-CH3OH)(CH3OH)2][ClO4]3·10H2O}2 (4), and {[Cu6(L5)(μ6-BO3)(μ-CH3CO2)(μ-CH3O)(CH3OH)][BF4]·13CH3OH·8H2O}2 (5). A polymeric side product {[Cu2(H2L2)(CH3OH)(BF4)][BF4]}n (6), involving a 2 + 2 macrocyclic ligand, was also isolated and structurally characterized.

Myeloid-derived microRNAs, miR-223, miR27a, and miR-652, are dominant players in myeloid regulation.

In the past few years expanding knowledge has been accumulated about the role of microRNAs (miRNAs) not only in hematopoiesis and cancer, but also in inflammatory and infectious diseases. Regarding myeloid cells, our knowledge is relatively insufficient, therefore we intended to collect the available data of miRNA profiles of myeloid cells. In addition to a rather general myeloid regulator miR-223, two other miRNAs seem to be useful subjects in understanding of myeloid miRNA biology: miR-27a and miR-652.

Critical role of extracellular vesicles in modulating the cellular effects of cytokines.

Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analyzed.

Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer.

The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model.

Effects of mitotane on gene expression in the adrenocortical cell line NCI-H295R: a microarray study.

Aim: The adrenolytic agent mitotane is widely used in the treatment of adrenocortical cancer; however, its mechanism of action is poorly elucidated. We have studied mitotane-induced mRNA expression changes in the NCI-H295R adrenocortical cancer cell line.

Materials & Methods: Cell viability and hormone assays were used to select the optimal mitotane concentration effectively inhibiting hormone secretion without affecting cell viability.

Both freshly prepared and frozen-stored amniotic membrane cells express the complement inhibitor CD59.

Amniotic membrane proved to be very effective tool in the treatment of a number of ocular surface diseases. The amniotic membrane, however, has to be stored before its transplantation onto the ocular surface followed by mandatory serologic control in order to exclude the transmission of certain viruses. Therefore it is most important to study if cryopreservation of the membrane affects cell surface expression of the molecules.

Lymphocytes from rheumatoid arthritis patients have elevated levels of intracellular peroxiredoxin 2, and a greater frequency of cells with exofacial peroxiredoxin 2, compared with healthy human lymphocytes.

Peroxiredoxin 2 has immune regulatory functions, but its expression in human peripheral blood lymphocytes and levels in extracellular fluid in healthy subjects and rheumatoid arthritis patients are poorly described. In the present study, the median intracellular peroxiredoxin 2 protein content of lymphocytes from rheumatoid arthritis patients was more than two-fold higher compared with healthy subjects' lymphocytes. Intracellular peroxiredoxin 3 levels were similar in healthy and rheumatoid arthritis lymphocytes.

A novel galectin-1 and interleukin 2 receptor β haplotype is associated with autoimmune myasthenia gravis.

Galectin-1 (LGALS1) and interleukin receptor 2β (IL2Rβ) are regulators of T-cell activation. Here we evaluated the association of regulatory region polymorphisms of the LGALS1 (rs4820293, rs4820294) and IL2Rβ (rs743777, rs228941) genes in 146 Caucasian myasthenia gravis patients compared to 291 ethnically matched controls. A significant difference was found in the distribution of the rs4820293/rs743777 polymorphism haplotypes (p<0.

Histamine suppresses fibulin-5 and insulin-like growth factor-II receptor expression in melanoma.

We previously showed that transgenic enhancement of histamine production in B16-F10 melanomas strongly supports tumor growth in C57BL/6 mice. In the present study, gene expression profiles of transgenic mouse melanomas, secreting different amounts of histamine, were compared by whole genome microarrays. Array results were validated by real-time PCR, and genes showing histamine-affected behavior were further analyzed by immunohistochemistry.

Impact of systemic histamine deficiency on the crosstalk between mammary adenocarcinoma and T cells.

The purpose of the present study was to investigate the influence of lack of histamine (HA) on tumor growth and functions of T cells in order further to illustrate the mechanism of immunological tolerance induction by HA. We assessed the phenotype and cytokine production of splenic lymphocytes in syngeneic HA-free (histidine decarboxylase knock-out) (HDC KO) and wild-type mice, inoculated subcutaneously with the LM2 murine breast cancer cell line. Relative quantification of target mRNA was performed with a TaqMan real-time RT-PCR assay.

HtrA1 is a novel mast cell serine protease of mice and men.

Mast cells are rich sources of proteases, such as tryptases and chymases that control many physiological and pathological processes, for example vascular permeability, smooth muscle cell proliferation or extracellular matrix remodeling. Murine mucosal mast cells mature under the influence of TGF-beta and play a role in asthmatic and anti-helminthic immune responses. In an attempt to identify novel genes that are highly upregulated during mucosal mast cell differentiation, we detected HtrA1 protease as a novel protein in mast cells by microarray experiments.

TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells.

Many studies detect elevated numbers of mast cells in tumors, but it is still controversial whether they are beneficial or detrimental for tumor cells. Furthermore, many tumors, such as melanomas, produce large quantities of transforming growth factor (TGF)-beta and during tumorigenesis the apoptotic and growth-inhibitory effects of TGF-betas are lost. Based on these data we investigated the gene expression changes in TGF-betaI-treated human mast cells with DNA microarray and detected 45 differentially regulated genes, among them T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3).

Phenotypic profiling of engineered mouse melanomas with manipulated histamine production identifies histamine H2 receptor and rho-C as histamine-regulated melanoma progression markers.

In the present study, the impact of acquired neoplastic L-histidine decarboxylase (HDC) expression, and its direct consequence, the release of histamine in the tumor environment, was assessed on melanoma tumor progression. B16-F10 mouse melanoma cells were manipulated via stable transfection, and nine novel transgenic variants were generated in triplicates, constitutively expressing the full-length sense mouse HDC mRNA, a mock control, and an antisense HDC RNA segment, respectively. Establishing both primary skin tumors and lung metastases in C57BL/6 mice, the nine variants with different histamine-releasing capacities were subjected to a comprehensive comparative progression profiling in vivo.

Effect of UVA radiation on membrane fluidity and radical decay in human fibroblasts as detected by spin labeled stearic acids.

The ultraviolet A (UVA) radiation component of sunlight (320-400 nm) has been shown to be a source of oxidative stress to cells via generation of reactive oxygen species. We report here some consequences of the UVA irradiation on cell membranes detected by electron paramagnetic resonance (EPR) spectroscopy. Paramagnetic nitroxide derivatives of stearic acid bearing the monitoring group at different depths in the hydrocarbon chain were incorporated into human fibroblasts membranes to analyze two main characteristics: kinetics of the nitroxide reduction and membrane fluidity.

IL-9 increases the expression of several cytokines in activated mast cells, while the IL-9-induced IL-9 production is inhibited in mast cells of histamine-free transgenic mice.

Histamine and IL-9 are suspected to play an important role in the pathogenesis of asthmatic and allergic reactions. Mast cells store a large amount of histamine in their granules and are capable of producing different cytokines upon stimulation. In this study we show that mast cells stimulated by IL-9 and ionomycin or IL-9 and antigen-specific IgE/antigen express several cytokines at mRNA level, among them are IL-5, IL-4, IL-10, IL-9, IL-13, IL-1beta, IL-1Ra, IL-6 and MIF.

High leptin level is accompanied with decreased long leptin receptor transcript in histamine deficient transgenic mice.

Leptin is a multifunctional cytokine and hormone that primarily acts in the hypothalamus and plays a key role in regulation of food intake and energy expenditure. Leptin acts through its receptor (OBR), the product of db gene that activates the Jak/STAT pathway predominantly. To exert its functions, leptin interacts with histamine as well.

Leptin-induced signal transduction pathways.

Leptin is a multifunctional cytokine and hormone that primarily acts in the hypothalamus and plays a key role in the regulation of food intake and energy expenditure. In addition, it has direct effects on many cell types on the periphery. Leptin acts through its receptor, the product of the db gene, which has six isoforms.