Adv Exp Med Biol
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Outcome after traumatic brain injury (TBI) is worsened by hemorrhagic shock (HS); however, the existing volume expansion approach with resuscitation fluids (RF) is controversial as it does not adequately alleviate impaired microvascular cerebral blood flow (mCBF). We previously reported that resuscitation fluid with drag reducing polymers (DRP-RF) improves CBF by rheological modulation of hemodynamics. Here, we evaluate the efficacy of DRP-RF, compared to lactated Ringers resuscitation fluid (LR-RF), in reducing cerebral microthrombosis and reperfusion mitochondrial oxidative stress after TBI complicated by HS. ⋯ Post-mortem whole-brain visualization of DiI painted vessels revealed multiple microthromboses in both hemispheres that were 29 ± 3% less in DRP-RF vs. LR-RF group (p < 0.05). Resuscitation after TBI/HS using DRP-RF effectively restores mCBF, reduces hypoxia, microthrombosis formation, and mitochondrial oxidative stress compared to conventional volume expansion with LR-RF.
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There are several mechanisms that cause memory impairment, including motivated forgetting, active forgetting, natural decay, and memory interference. Interference occurs when one is attempting to recall something specific, but there is conflicting information making it more difficult to recall the target stimuli. In laboratory settings, it is common to measure memory interference with paired associate tasks-usually utilizing the AB-CD, AB-AC, AB-ABr, or AB-DE AC-FG method. ⋯ The memory effects of each condition differ, but are all related to alterations in brain physiology and general memory deterioration. Exercise, or physical activity, has been demonstrated to attenuate memory interference in some cases, but the mechanisms are still being determined. Further research is needed on memory interference, in regard to exercise and neuropsychiatric disorders.
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The field of cancer therapy has been revolutionized through the use of immunotherapy, and treatment with these therapies now spans from early to late stage, and even into prevention. However, there are still a significant proportion of patients who do not derive long-term benefit from monotherapy and even combined therapy regimens, and novel approaches are needed to enhance therapeutic responses. Additionally, ideal biomarkers of response to immunotherapy are lacking and are critically needed. ⋯ The field of microbiome research in immuno-oncology is quickly emerging, with the potential use of the microbiome (in the gut as well as in the tumor) as a biomarker for response to IO as well as a therapeutic target. Notably, the microbiome may even have a role in toxicity to therapy. The state of the science in microbiome and IO are discussed and caveats and future directions are outlined to provide insights as we move forward as a field.
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As a classical form of programmed cell death, autophagy is widely involved in cellular metabolism and vital for the maintenance of homeostasis in physiological and pathological states. With multiple levels of regulation and signaling integrated in, autography presents complicated relevance with various diseases, such as cancer and neurological diseases. The emerging subject, systems biology, along with multi-omics approaches, offers a new strategy to investigate these interactive processes from a holistic perspective. ⋯ The critical step of systematic study is to explore interplay between biological molecules based on massive biological data, which requires construction of networks in different biological levels, modification, and identification of key pathways and targets via optimized algorithm and experimental verification. Guided by systems biology research, drug design can thus be strengthened by efficient screening and accurate evaluation. Overall, systems biology promises to act as a powerful tool which both helps to clarify the profound mechanism and to develop efficacious medicine.
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The growing success of immune checkpoint inhibitors (ICIs) has led to effectively treating several types of cancers. Even though their use has been associated with the development of cardiac adverse effects, which may decrease the overall survival in cancer patients. ⋯ Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest. We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.