Sex-specific immune alterations in mice following long-term simulated microgravity and chronic irradiation.

Given NASA's plans for manned lunar and Mars missions, it is critical to assess the risk of splenic immune dysregulation by using ground-based models of simulated microgravity (SMG) and/or chronic irradiation (CIR). To address this, C57BL/6 J mice of both sexes exposed to SMG and/or CIR for 29 days and alterations in immune cell distribution, function and phenotype were assessed. SMG and/or CIR altered a greater variety of immune cells in both lymphoid and myeloid lineages in female mice than in male mice; the function of splenic CD4 + T cells, CD8 + T cells, and CD19 + B cells altered in a sex-specific manner; and the distribution of different immune cells altered based on animal sex.

Azido derivatives of sesquiterpene lactones: Synthesis, anticancer proliferation, and chemistry of nitrogen-centered radicals.

Sesquiterpene lactones (SLs) such as parthenolide (PTL) and dehydroleucodine (DhL) selectively kill cancer cells without exerting normal tissue toxicity, potentially due to presence of α-methylene-γ-lactone (αMγL) fragment. We hypothesize that the addition of an azido group to the αMγL fragment of PTL or DhL further augments their anticancer properties as well as radiation sensitivity of cancer cells. Azido-SLs containing the azido group at the C14 methyl position of PTL (i.

Current Insights into Molecular Mechanisms and Potential Biomarkers for Treating Radiation-Induced Liver Damage.

Highly conformal delivery of radiation therapy (RT) has revolutionized the treatment landscape for primary and metastatic liver cancers, yet concerns persist regarding radiation-induced liver disease (RILD). Despite advancements, RILD remains a major dose-limiting factor due to the potential damage to normal liver tissues by therapeutic radiation. The toxicity to normal liver tissues is associated with a multitude of physiological and pathological consequences.

G-Banding and Molecular Cytogenetics Detect Novel Translocations and Cryptic Aberrations in Human Immortal Endothelial Cells.

Endothelial cells (ECs) maintain vessel tone and barrier integrity, regulate blood homeostasis, and prevent the extravasation of leukocytes under normal physiological conditions. Because of the limited lifespans and batch-to-batch differences with respect to the genetic make-up of primary ECs, established immortal EC lines are extensively used for studying endothelial biology. To address this issue, the immortal endothelial cell line EA.

Platelets, inflammation, and purinergic receptors in chronic kidney disease.

Platelets are anucleated cells that circulate in the bloodstream. Historically, platelets were thought to perform a singular function-stop bleeding via clotting. Although platelets do play a key role in hemostasis and thrombosis, recent studies indicate that platelets also modulate inflammation, and this platelet-induced inflammation contributes to the pathophysiology of various diseases such as atherosclerosis and diabetes mellitus.

Understanding the molecular mechanism responsible for developing therapeutic radiation-induced radioresistance of rectal cancer and improving the clinical outcomes of radiotherapy - A review.

Rectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence.

Protocol for preparation and staining of chromosomes isolated from mouse and human tissues for conventional and molecular cytogenetic analysis.

The study of chromosomes without or with molecular DNA probes provides crucial insight for understanding research findings, as well as refining diagnosis, prognosis, and therapeutics in clinical settings. Here, we present a protocol for chromosome preparation, conventional G-banding, locus-specific fluorescent in situ hybridization, and spectral karyotyping for both mouse and human samples. This protocol optimizes the preparation of chromosomes from mouse and human cells for subsequent conventional and molecular cytogenetic analysis.

Tocotrienols Provide Radioprotection to Multiple Organ Systems through Complementary Mechanisms of Antioxidant and Signaling Effects.

Tocotrienols have powerful radioprotective properties in multiple organ systems and are promising candidates for development as clinically effective radiation countermeasures. To facilitate their development as clinical radiation countermeasures, it is crucial to understand the mechanisms behind their powerful multi-organ radioprotective properties. In this context, their antioxidant effects are recognized for directly preventing oxidative damage to cellular biomolecules from ionizing radiation.

Evaluating the effects of low-dose simulated galactic cosmic rays on murine hippocampal-dependent cognitive performance.

Space exploration has advanced substantially over recent decades and plans to increase the duration of deep space missions are in preparation. One of the primary health concerns is potential damage to the central nervous system (CNS), resulting in loss of cognitive abilities and function. The majority of ground-based research on space radiation-induced health risks has been conducted using single particle simulations, which do not effectively model real-world scenarios.

Radiation-Induced Intestinal Normal Tissue Toxicity: Implications for Altered Proteome Profile.

Radiation-induced toxicity to healthy/normal intestinal tissues, especially during radiotherapy, limits the radiation dose necessary to effectively eradicate tumors of the abdomen and pelvis. Although the pathogenesis of intestinal radiation toxicity is highly complex, understanding post-irradiation alterations in protein profiles can provide crucial insights that make radiotherapy safer and more efficient and allow for increasing the radiation dose during cancer treatment. Recent preclinical and clinical studies have advanced our current understanding of the molecular changes associated with radiation-induced intestinal damage by assessing changes in protein expression with mass spectrometry-based approaches and 2-dimensional difference gel electrophoresis.

Cytogenetic and epigenetic aberrations in peripheral lymphocytes of northwest Arkansas Marshallese.

Purpose: Nuclear weapons testing in the northern Marshall Islands between 1946 and 1958 resulted in ionizing radiation (IR) exposure of the thousands of Marshallese. Furthermore, numerous islands were contaminated by radioactive fallout. Significant increases in cancer and metabolic syndrome incidences have been reported among Marshallese, and potential for further increases looms due to the latency of radiation-induced health effects.

Molecular Cytogenetics Reveals Mosaicism in Human Umbilical Vein Endothelial Cells.

Primary human umbilical vein endothelial cells (HUVECs) are consistently the most reliable in vitro model system for studying the inner lining of blood and lymphatic vessels or the endothelium. Primary human cells originate from freshly isolated tissues without genetic manipulation and generally show a modal number of 46 chromosomes with no structural alterations, at least during early passages. We investigated the cytogenetic integrity of HUVECs with conventional (G-banding) and molecular cytogenetic methods (spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH)).

Ionizing Radiation Activates Mitochondrial Function in Osteoclasts and Causes Bone Loss in Young Adult Male Mice.

The damaging effects of ionizing radiation (IR) on bone mass are well-documented in mice and humans and are most likely due to increased osteoclast number and function. However, the mechanisms leading to inappropriate increases in osteoclastic bone resorption are only partially understood. Here, we show that exposure to multiple fractions of low-doses (10 fractions of 0.

Synthetic Matrices for Intestinal Organoid Culture: Implications for Better Performance.

Organoids are three-dimensional (3D) self-renewing and self-organizing clusters of cells that imitate an organ's structure and function, making them an important tool in various fields ranging from regenerative medicine to drug discovery. Organoids can be developed by isolating adult stem cells from an organ-specific tissue (e.g.

Platelet glycoprotein Ibα provides radiation protection.

Background And Purpose: Platelet membrane glycoprotein Ibα (GPIbα), the major ligand-binding subunit of the GPIb-IX-V complex, binds to a number of ligands contributing to hemostasis, thrombosis, and inflammation. Binding to von Willebrand factor (VWF) initiates the process of hemostasis/thrombosis, while binding to the leukocyte receptor Macrophage-1 antigen (Mac-1) has been implicated in modulating the inflammatory response. Thus as GPIbα resides at the nexus of thrombosis and inflammation, we investigated the impact of GPIbα on radiation injury outcomes as this injury triggers both the thrombotic and inflammatory pathways.

Mitigation of late cardiovascular effects of oxygen ion radiation by γ-tocotrienol in a mouse model.

Purpose: While there is concern about degenerative tissue effects of exposure to space radiation during deep-space missions, there are no pharmacological countermeasures against these adverse effects. γ-Tocotrienol (GT3) is a natural form of vitamin E that has anti-oxidant properties, modifies cholesterol metabolism, and has anti-inflammatory and endothelial cell protective properties. The purpose of this study was to test whether GT3 could mitigate cardiovascular effects of oxygen ion (O) irradiation in a mouse model.

Plasma Metabolomics in a Nonhuman Primate Model of Abdominal Radiation Exposure.

The acute radiation syndrome is defined in large part by radiation injury in the hematopoietic and gastrointestinal (GI) systems. To identify new pathways involved in radiation-induced GI injury, this study assessed dose- and time-dependent changes in plasma metabolites in a nonhuman primate model of whole abdominal irradiation. Male and female adult Rhesus monkeys were exposed to 6 MV photons to the abdomen at doses ranging between 8 and 14 Gy.

Differential Recovery of Small Intestinal Segments after Partial-Body Irradiation in Non-Human Primates.

In the event of a radiological attack or accident, it is more likely that the absorbed radiation dose will be heterogeneous, rather than uniformly distributed throughout the body. This type of uneven dose distribution is known as partial-body irradiation (PBI). Partial exposure of the vital organs, specifically the highly radiosensitive intestines, may cause death, if the injury is significant and the post-exposure recovery is considerably compromised.

Dietary Methionine Deficiency Enhances Genetic Instability in Murine Immune Cells.

Both cell and animal studies have shown that complete or partial deficiency of methionine inhibits tumor growth. Consequently, the potential implementation of this nutritional intervention has recently been of great interest for the treatment of cancer patients. Unfortunately, diet alteration can also affect healthy immune cells such as monocytes/macrophages and their precursor cells in bone marrow.

Simultaneous exposure to chronic irradiation and simulated microgravity differentially alters immune cell phenotype in mouse thymus and spleen.

Deep-space missions may alter immune cell phenotype in the primary (e.g., thymus) and secondary (e.

Dietary Methionine Supplementation Exacerbates Gastrointestinal Toxicity in a Mouse Model of Abdominal Irradiation.

Background And Purpose: Identification of appropriate dietary strategies for prevention of weight and muscle loss in cancer patients is crucial for successful treatment and prolonged patient survival. High-protein oral nutritional supplements decrease mortality and improve indices of nutritional status in cancer patients; however, high-protein diets are often rich in methionine, and experimental evidence indicates that a methionine-supplemented diet (MSD) exacerbates gastrointestinal toxicity after total body irradiation. Here, we sought to investigate whether MSD can exacerbate gastrointestinal toxicity after local abdominal irradiation, an exposure regimen more relevant to clinical settings.

Fractionated radiation suppresses Kruppel-like factor 2 pathway to a greater extent than by single exposure to the same total dose.

Kruppel-like factor 2 (KLF2) is a positive transcriptional regulator of several endothelial protective molecules, including thrombomodulin (TM), a surface receptor, and endothelial nitric oxide synthase (eNOS), an enzyme that generates nitric oxide (NO). Loss of TM and eNOS causes endothelial dysfunction, which results in suppressed generation of activated protein C (APC) by TM-thrombin complex and in upregulation of intercellular adhesion molecule 1 (ICAM-1). Mechanistic studies revealed that activation of extracellular signal-regulated kinase 5 (ERK5) via upregulation of myocyte enhancer factor 2 (MEF2) induces KLF2 expression.

Methionine dietary supplementation potentiates ionizing radiation-induced gastrointestinal syndrome.

Methionine is an essential amino acid needed for a variety of processes in living organisms. Ionizing radiation depletes tissue methionine concentrations and leads to the loss of DNA methylation and decreased synthesis of glutathione. In this study, we aimed to investigate the effects of methionine dietary supplementation in CBA/CaJ mice after exposure to doses ranging from 3 to 8.

Identification of novel breakpoints for locus- and region-specific translocations in 293 cells by molecular cytogenetics before and after irradiation.

The human kidney embryonic 293 cell line (293 cells) is extensively used in biomedical and pharmaceutical research. These cells exhibit a number of numerical and structural chromosomal anomalies. However, the breakpoints responsible for these structural chromosomal rearrangements have not been comprehensively characterized.