| 1. |
- Li, Wei, et al.
(författare)
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Soluble Immune Checkpoints Are Dysregulated in COVID-19 and Heavy Alcohol Users With HIV Infection
- 2022
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Ingår i: FRONTIERS IN IMMUNOLOGY. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Immune checkpoints (ICPs) consist of paired receptor-ligand molecules that exert inhibitory or stimulatory effects on immune defense, surveillance, regulation, and self-tolerance. ICPs exist in both membrane and soluble forms in vivo and in vitro. Imbalances between inhibitory and stimulatory membrane-bound ICPs (mICPs) in malignant cells and immune cells in the tumor immune microenvironment (TIME) have been well documented. Blockades of inhibitory mICPs have emerged as an immense breakthrough in cancer therapeutics. However, the origin, structure, production regulation, and biological significance of soluble ICPs (sICPs) in health and disease largely remains elusive. Soluble ICPs can be generated through either alternative mRNA splicing and secretion or protease-mediated shedding from mICPs. Since sICPs are found in the bloodstream, they likely form a circulating immune regulatory system. In fact, there is increasing evidence that sICPs exhibit biological functions including (1) regulation of antibacterial immunity, (2) interaction with their mICP compartments to positively or negatively regulate immune responses, and (3) competition with their mICP compartments for binding to the ICP blocking antibodies, thereby reducing the efficacy of ICP blockade therapies. Here, we summarize current data of sICPs in cancer and infectious diseases. We particularly focus on sICPs in COVID-19 and HIV infection as they are the two ongoing global pandemics and have created the world's most serious public health challenges. A "storm" of sICPs occurs in the peripheral circulation of COVID-19 patients and is associated with the severity of COVID-19. Similarly, sICPs are highly dysregulated in people living with HIV (PLHIV) and some sICPs remain dysregulated in PLHIV on antiretroviral therapy (ART), indicating these sICPs may serve as biomarkers of incomplete immune reconstitution in PLHIV on ART. We reveal that HIV infection in the setting of alcohol misuse exacerbates sICP dysregulation as PLHIV with heavy alcohol consumption have significantly elevated plasma levels of many sICPs. Thus, both stimulatory and inhibitory sICPs are present in the bloodstream of healthy people and their balance can be disrupted under pathophysiological conditions such as cancer, COVID-19, HIV infection, and alcohol misuse. There is an urgent need to study the role of sICPs in immune regulation in health and disease.
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| 2. |
- Wang, Fang, et al.
(författare)
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A NUMERICAL STUDY ON CORRELATION OF RIB FRACTURES WITH THORACIC INJURY CRITERIA IN OBLIQUE IMPACT
- 2017
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Ingår i: Journal of Mechanics in Medicine and Biology. - 0219-5194. ; 17:8
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Tidskriftsartikel (refereegranskat)abstract
- Thoracic injury is one of the vital issues in vehicle side crashes. Experiments have been done widely to study thoracic injuries using biological subjects but less virtual tests were made by using Finite Element (FE) models. This study aimed at determining the correlation of the computationally calculated thoracic injury (Number of Rib Fractures NRF) with existing thoracic injury criteria under pure side and oblique impacts. For this purpose, a previously developed thorax FE model was validated by using Post Mortem Human Subject (PMHS) tests in pure side and oblique impacts in this study. The rib fractures were reconstructed and compared with the fractures observed in the PMHS tests. The model was then used to simulate rib fractures in human thorax impactor tests at Principal Direction of Force (PDOF) angles of 90 degrees to 35 degrees (total of 12 impacts). Furthermore, the normalized NRF were calculated and analyzed for comparing with normalized simulated injury parameters based on various human thoracic injury criteria, including contact force criterion, thorax deflection criterion, compression criterion, upper spine acceleration criterion and Thoracic Trauma Index (TTI). It is suggested that the TTI criterion has better correlation with the NRF than the other injury criteria.
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