Both alpha-synuclein aggregation and iron deposits are neuropathological hallmarks of Parkinson’s disease (PD). We are particularly interested in whether iron could synergize with alpha-synuclein pathology in vivo, especially in the nigrostriatal system. In the present study, we reported transgenic mice with overexpressing human A53T alpha-synuclein, as well as WT mice with high dietary iron displayed hyperactive motor coordination and impaired colonic motility, compared with those with basal dietary iron. Only A53T mice, but not WT mice with high dietary iron exhibited nigral dopaminergic neuronal loss, lower levels of tyrosine hydroxylase (TH) in the substantia nigra (SN) and decreased dopamine contents in the striatum. Although there was no obvious elevation of iron contents in the SN in WT mice with high dietary iron, we observed iron contents in the SN were especially higher than the other brain regions in 12-month aged mice with either high or basal dietary iron. These results suggested high dietary iron supplement could induce nigral dopaminergic neurons lesion in A53T mice, which might be due to the vulnerability of SN to accumulate iron.
We aimed to review and discuss some of the latest research results related to post-burn pathophysiological changes and provide some clues for future study.Background: Burns are one of the most common and serious traumas and consist of a series of pathophysiological changes of thermal injury. Accompanied by thermal damage to skin and soft tissues, inflammatory mediators are released in large quantities. Changes in histamine, bradykinin, and cytokines such as vascular endothelial growth factor (VEGF), metabolic factors such as adenosine triphosphate (ATP), and activated neutrophils all affect the body's vascular permeability.Methods: We searched articles with subject words "microvascular permeability", "burn" "endothelium", and "endothelial barrier" in PubMed in English published from the beginning of database to Dec, 2020.
Conclusions:The essence of burn shock is the rapid and extensive fluid transfer in burn and non-burn tissue. After severe burns, the local and systemic vascular permeability increase, causing intravascular fluid extravasation, leading to a progressive decrease in effective circulation volume, an increase in systemic vascular resistance, a decrease in cardiac output, peripheral tissue edema, multiple organ failure, and even death. There are many cells, tissues, mediators and structures involved in the pathophysiological process of the damage to vascular permeability. Ulinastatin is a promising agent for this problem.
As an aggressive subtype of breast cancer, triple-negative breast cancer (TNBC) is associated with poor prognosis and lack of effective therapy, except chemotherapy. In recent years, immunotherapy based on immune checkpoint (IC) inhibition has emerged as a promising therapeutic strategy in TNBC. TNBC has more tumor-infiltrating lymphocytes (TILs) and higher rate of mutation and programmed cell death ligand-1 (PD-L1) expression than other subtypes of breast cancer have. However, previous studies have shown that monotherapy has little efficacy and only some TNBC patients can benefit from immunotherapy. Therefore, it is important to identify biomarkers that can predict the efficacy of IC inhibitors (ICIs) in TNBC. Recently, various biomarkers have been extensively explored, such as PD-L1, TILs and tumor mutational burden (TMB). Clinical trials have shown that PD-L1-positive patients with advanced TNBC benefit from ICIs plus chemotherapy. However, in patients with early TNBC receiving neoadjuvant therapy, PD-L1 cannot predict the efficacy of ICIs. These inconsistent conclusions suggest that PD-L1 is the best to date but an imperfect predictive biomarker for efficacy of ICIs. Other studies have shown that advanced TNBC patients with TMB ≥10 mutations/Mb can achieve clinical benefits from pembrolizumab. TILs also have potential predictive value in TNBC. Here, we select some biomarkers related to ICIs and discuss their potential predictive and prognostic value in TNBC. We hope these biomarkers could help to identify suitable patients and realize precision immunotherapy.
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