Knowledge of the time of deposition is pivotal in forensic investigations. Recent studies show that changes in intrinsic fluorescence over time can be used to estimate the age of body fluids. These changes have been attributed to oxidative modifications caused by protein–lipid interactions. This pilot study aims to explore the impact of these modifications on body fluid fluorescence, enhancing the protein–lipid model system for age estimation. Lipid and protein oxidation markers, including protein carbonyls, dityrosine, advanced glycation end-products (AGEs), malondialdehyde (MDA), and 4-hydroxynonenal (HNE), were studied in aging semen, urine, and saliva over 21 days. Surface plasmon resonance imaging (SPRi), enzyme-linked immunosorbent assay (ELISA), and fluorescence spectroscopy were applied. Successful detection of AGE, dityrosine, MDA, and HNE occurred in semen and saliva via SPRi, while only dityrosine was detected in urine. Protein carbonyls were measured in all body fluids, but only in saliva was a significant increase observed over time. Additionally, protein fluorescence loss and fluorescent oxidation product formation were assessed, showing significant decreases in semen and saliva, but not in urine. Although optimization is needed for accurate quantification, this study reveals detectable markers for protein and lipid oxidation in aging body fluids, warranting further investigation.
MULTIFILE
Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.
DOCUMENT
According to the "membrane sensor" hypothesis, the membrane's physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy.
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