Int J Med Sci
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Background: Although whole-body cooling has been reported to improve the ischemic/reperfusion injury in hemorrhagic shock (HS) resuscitation, it is limited by its adverse reactions following therapeutic hypothermia. HS affects the experimental and clinical bowel disorders via activation of the brain-gut axis. It is unknown whether selective brain cooling achieves beneficial effects in HS resuscitation via preserving the integrity of the brain-gut axis. ⋯ Intrajugular-based infusion cooled the brain robustly with a minimal effect on body temperature. This brain cooling significantly reduced the HS resuscitation-induced gut disruption, systemic inflammation, and peripheral vital organ injuries in rats. Conclusion: Resuscitation with selective brain cooling achieves peripheral vital organs protection in hemorrhagic shock resuscitation via preserving the integrity of the brain-gut axis.
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Premature ovarian failure (POF) is a typical form of pathological aging with complex pathogenesis and no effective treatment. Meanwhile, recent studies have reported that a high-fat and high-sugar (HFHS) diet adversely affects ovarian function and ovum quality. Here, we investigated the therapeutic effect of thymopentin (TP-5) as a treatment for murine POF derived from HFHS and its target. ⋯ Additionally, compared with the control groups, the expression levels of interleukin, NFκB, and TNF families of genes were significantly downregulated in the POF+TP-5 group, whereas expression of the TGFβ/Smad9 genes was significantly upregulated. Finally, immunofluorescence staining and qPCR confirmed that TP-5 promoted the polarization of Mø2 cells in the ovary by activating the expression of the BMP4/Smad9 signalling pathway. Thus, our study confirmed that TP-5 has a significant therapeutic effect on POF by upregulating BMP4/Smad9 signalling pathway so as to promote the balance and polarization of immune cell and reducing the release of inflammatory factors and reduce lipid oxidative stress injury.
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A new Danshensu/tetramethylpyrazine derivative (ADTM) with cardio-protection effects such as antioxidant, arterial relaxation, pro-angiogenesis and antiplatelet activities. Platelet activating factor receptor (PAFR) plays a key role in myocardial ischemia reperfusion (MIR) injury. This study aims to investigate the protective role of ADTM in MIR injury and clarify the potential role of PAFR. ⋯ At the same time, ADTM and PAFR small interfering RNA (siRNA) could inhibit cardiomyocytes apoptosis and inflammation during HR, while PAF presents the opposite effect. Furthermore, the above effects of PAF in HR induced cardiomyocytes were reversed by co-treatment of ADTM. Our findings demonstrate for the first time that ADTM protects against MIR injury through inhibition of PAFR signaling, which provides a new treatment for MIR.
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Traumatic brain injury (TBI) is a major cause of death and disability worldwide. A sequence of pathological processes occurred when there is TBI. Previous studies showed that sphingosine-1-phosphate receptor 1 (S1PR1) played a critical role in inflammatory response in the brain after TBI. ⋯ Furthermore, treatment with FTY720 not only improved neurological function, but also increased the survival rate of mice significantly. These findings suggest that FTY720 administration restored the structure of the NVU after experimental TBI by decreasing endothelial cell apoptosis and attenuating the activation of astrocytes. Moreover, FTY720 might reduce inflammation in the brain by reducing the activation of microglia in TBI mice.
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Background: Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity. ⋯ Conversely, in the current study, we show that CRAMP-/- mice are more susceptible to the rhabdomyolysis model of AKI. A more in-depth investigation of wild-type and CRAMP-/- mice revealed important differences in the levels of several inflammatory mediators. Conclusion: Cathelicidins can induce a varied and even opposing repertoire of immune-inflammatory responses depending on the subjacent disease and the cellular context.