Cyclic peptides (Shandong University)

Chlorinated paraffins (CPs) are complex mixture of chlorinated straight-chain hydrocarbons, including short-, medium-, and long-chain CPs (SCCPs, MCCPs, and LCCPs), to which humans are exposed environmentally. Although PM_2.5-bound CPs were positively associated with asthma and related symptoms, the toxicological effects of CPs on the respiratory system remain limitedly understood. CPs were extracted from PM_2.5 samples collected in three cities in southern China, representing distinct SCCPs, MCCPs, and LCCPs profiles. The A549/THP-1 co-culture cells, an in vitro respiratory model, were exposed to PM_2.5-derived extracts containing CPs (CP extract). The gradient was established according to the extract dosage calibrated based on its quantified SCCP content with environmentally relevant concentrations. Cell viability, oxidative stress, inflammatory factors, cell cycle distribution, and genotoxicity were assessed. CP extracts reduced cell viability, increased pro-inflammatory factors concentrations, induced cell cycle arrest and DNA damage. Furthermore, CP mixtures were prepared using standards to simulate PM_2.5-relevant compositions. But the results showed weak toxicological effects of CP mixtures, suggesting CPs play a relatively weak role or CPs exhibit toxicological effects through alternative pathways. Interesting, varying compositional ratios of SCCPs, MCCPs, and LCCPs may induce different cytotoxic effects. These findings provide in vitro evidence for explaining adverse effects of PM_2.5-bound CPs on A549/THP-1 cells. More research is needed to clarify the respiratory toxicological effects of CPs.

Normothermic regional perfusion (NRP) is increasingly implemented to optimize the outcome of transplantation from donors undergoing circulatory determination of death. NRP shortens the duration of warm ischemia, allowing splanchnic reperfusion with oxygenated blood. This supports the abdominal organs throughout recovery, allowing for their thorough assessment, avoids the need for rapid recovery, and restores a near physiological environment. However, after NRP, the grafts are exposed to a period of cold ischemia preceding further evaluation and reconditioning through ex situ machine perfusion or direct transplantation. The duration of cold ischemic time may be extremely variable. During cold ischemic time, the liver and the kidneys are indirectly protected by a decrease in metabolic demands induced by deep hypothermia. To optimize protection, the hypothermic state is initiated in situ, immediately after extracorporeal blood flow interruption, via topical cooling with sterile ice and intravascular cooling. The latter is usually induced by the administration of cold preservation solution (CPS) by gravity. We performed an observational study to assess the feasibility, safety, and effectiveness of a controlled strategy of CPS administration and oxygenation employing the NRP circuit and cannulae in controlled circulatory determination of death undergoing abdominal NRP. This approach provided a controlled, fast, and consistent flow, ensuring a prompt induction of hypothermia. Moreover, during CPS administration, the delivery of a fresh gas flow through the membrane lung resulted effective in significantly increasing the oxygen tension in the CPS. The hyperoxygenation of the blood-free perfusate might provide a metabolic substrate to the cells, preconditioning the grafts before cold ischemia.