Interactions of ruthenium(II) polypyridyl complexes with human telomeric DNA.

Eight [Ru(bpy)2L]2+ and three [Ru(phen)2L]2+complexes (where bpy = 2,2'-bipyridine and phen = 1,10-phenanthroline are ancillary ligands, and L = a polypyridyl experimental ligand) were investigated for their G-quadruplex binding abilities. Fluorescence resonance energy transfer melting assays were used to screen these complexes for their ability to selectively stabilize human telomeric DNA variant, Tel22. The best G-quadruplex stabilizers were further characterized for their binding properties (binding constant and stoichiometry) using UV-vis, fluorescence spectroscopy, and mass spectrometry. The ligands' ability to alter the structure of Tel22 was determined via circular dichroism and PAGE studies. We identified me2allox as the experimental ligand capable of conferring excellent stabilizing ability and good selectivity to polypyridyl Ru(II) complexes. Replacing bpy by phen did not significantly impact interactions with Tel22, suggesting that binding involves mostly the experimental ligand. However, using a particular ancillary ligand can help fine-tune G-quadruplex-binding properties of Ru(II) complexes. Finally, the fluorescence "light switch" behavior of all Ru(II) complexes in the presence of Tel22 G-quadruplex was explored. All Ru(II) complexes displayed "light switch" properties, especially [Ru(bpy)2(diamino)]2+, [Ru(bpy)2(dppz)]2+, and [Ru(bpy)2(aap)]2+. Current work sheds light on how Ru(II) polypyridyl complexes interact with human telomeric DNA with possible application in cancer therapy or G-quadruplex sensing.

Denosumab as a Pharmacological Countermeasure Against Osteopenia in Long Duration Spaceflight.

INTRODUCTION: Prolonged exposure to microgravity is associated with a significant reduction in bone density, exposing astronauts to renal calculi in flight and osteoporotic fractures on return to Earth. While physical countermeasures and bisphosphonates may reduce demineralization, additional therapies are needed for future interplanetary missions. This literature review aims to understand the current background pertaining to denosumab (a monoclonal antibody therapy used in osteoporosis) and its potential use for long duration spaceflight.METHOD: A literature review was conducted using the following keywords: "osteoporosis"; "osteopaenia"; "microgravity"; "space flight"; "bed rest"; "denosumab"; "alendronate"; "bisphosphonates"; and "countermeasures". Additional articles were identified through references. Included for discussion were 48 articles, including systemic reviews, clinical trials, practice guidelines, and textbooks.RESULTS: No previous bed rest or in-flight studies regarding denosumab were identified. In osteoporosis, denosumab is superior to alendronate in maintaining bone density with a lower rate of side-effects. Emerging evidence in reduced biomechanical loading state suggests denosumab improves bone density and decreases fracture risk. Concerns exists over vertebral fracture risk following discontinuation. The dosing regimen of denosumab offers practical advantages over bisphosphonates. Existing spaceflight studies with alendronate serve as a template for a study with denosumab and allow for a direct comparison of efficacy and safety.DISCUSSION: Denosumab has numerous potential advantages as a countermeasure to microgravity-induced osteopenia when compared to alendronate, including: improved efficacy; fewer side-effects: better tolerability; and a convenient dosing regimen. Two further studies are proposed to determine in-flight efficacy and the suitability of monoclonal antibody therapy in the spaceflight environment.Rengel A, Tran V, Toh LS. Denosumab as a pharmacological countermeasure against osteopenia in long duration spaceflight. Aerosp Med Hum Perform. 2023; 94(5):389-395.

The Final Frontier: Palliative Care in Space is an Inevitability.

As space exploration becomes increasingly common, palliative care for astronauts will require greater consideration. All aspects of palliative care need to be specifically adapted for astronauts. For example, addressing additional circumstances such as inability to see loved ones from Earth will be an important part of meeting their psychological and spiritual needs. A different approach to pharmacological management of end-of-life symptoms is also warranted due to changes in human physiology and pharmacokinetics in space.

Space Medicines for Space Health.

Scientists from around the world are studying the effects of microgravity and cosmic radiation via the "off-Earth" International Space Station (ISS) laboratory platform. The ISS has helped scientists make discoveries that go beyond the basic understanding of Earth. Over 300 medical experiments have been performed to date, with the goal of extending the knowledge gained for the benefit of humanity. This paper gives an overview of these numerous space medical findings, critically identifies challenges and gaps, and puts the achievements into perspective toward long-term space traveling and also adding benefits to our home planet. The medical contents are trifold structured, starting with the well-being of space travelers (astronaut health studies), followed by medical formulation research under space conditions, and then concluding with a blueprint for space pharmaceutical manufacturing. The review covers essential elements of our Earth-based pharmaceutical research such as drug discovery, drug and formulation stability, drug-organ interaction, drug disintegration/bioavailability/pharmacokinetics, pathogen virulence, genome mutation, and body's resistance. The information compiles clinical, medicinal, biological, and chemical research as well as fundamentals and practical applications.

Mechanical and oral antibiotic bowel preparation in ovarian cancer debulking: Are we lowering or just trading surgical complications?

OBJECTIVES: To examine postoperative complications associated with preoperative mechanical and oral antibiotic bowel preparation (MOABP) for patients with ovarian cancer who underwent bowel resection at cytoreductive surgery (CRS). METHODS: This was a single-institution retrospective study of patients with ovarian cancer undergoing CRS from 01/2011-12/2020 using ICD-10 diagnoses and procedure codes. Patients were stratified by those who underwent bowel resection versus no resection. Bowel resection patients were further stratified by those who underwent MOABP versus no bowel preparation. Patient demographics, tumor data, and perioperative metrics were collected. Unadjusted and adjusted logistic regression evaluated odds of 30-day postoperative complications in patients with bowel resection versus no resection and those with MOABP versus no bowel preparation. RESULTS: Of 919 patients identified, 215 (23.3%) required bowel resection, which included 81 (37.7%) who received MOABP. Patient characteristics, co-morbidities, and cancer data were similar between MOABP versus no bowel preparation patients. MOABP patients underwent more interval CRS (34.6% versus 9.0%), more optimal surgical resections (96.3% versus 83.8%), fewer diverting ostomies (13.5% versus 33.5%), and shorter hospital stays (7.1 versus 9.4 days) than no bowel preparation patients. On adjusted analyses, MOABP patients experienced significantly lower odds of deep/organ-space surgical infections and 30-day readmissions but higher odds of unplanned intensive care unit (ICU) admissions and grade 3 or higher cardiac and gastrointestinal complications. CONCLUSIONS: Patients who underwent preoperative MOABP prior to ovarian cancer CRS with bowel resection had lower odds or deep/organ-space infections and readmissions, shorter hospital stays, fewer diverting ostomies, and more optimal resections. However, these patients also experienced higher odds of ICU admissions and grade 3 or higher cardiac and gastrointestinal complications. The positive and negative postoperative outcomes in this population should be considered in clinical practice.

Gluteal Muscle Atrophy and Increased Intramuscular Lipid Concentration Are Not Mitigated by Daily Artificial Gravity Following 60-Day Head-Down Tilt Bed Rest.

Exposure to spaceflight and head-down tilt (HDT) bed rest leads to decreases in the mass of the gluteal muscle. Preliminary results have suggested that interventions, such as artificial gravity (AG), can partially mitigate some of the physiological adaptations induced by HDT bed rest. However, its effect on the gluteal muscles is currently unknown. This study investigated the effects of daily AG on the gluteal muscles during 60-day HDT bed rest. Twenty-four healthy individuals participated in the study: eight received 30 min of continuous AG; eight received 6 × 5 min of AG, interspersed with rest periods; eight belonged to a control group. T1-weighted Dixon magnetic resonance imaging of the hip region was conducted at baseline and day 59 of HDT bed rest to establish changes in volumes and intramuscular lipid concentration (ILC). Results showed that, across groups, muscle volumes decreased by 9.2% for gluteus maximus (GMAX), 8.0% for gluteus medius (GMED), and 10.5% for gluteus minimus after 59-day HDT bed rest (all p < 0.005). The ILC increased by 1.3% for GMAX and 0.5% for GMED (both p < 0.05). Neither of the AG protocols mitigated deconditioning of the gluteal muscles. Whereas all gluteal muscles atrophied, the ratio of lipids to intramuscular water increased only in GMAX and GMED muscles. These changes could impair the function of the hip joint and increased the risk of falls. The deconditioning of the gluteal muscles in space may negatively impact the hip joint stability of astronauts when reexpose to terrestrial gravity.