Toppmckenzie2709
Endothelial colony-forming cells (ECFCs) are human vasculogenic cells described as potential cell therapy product and good candidates for being a vascular liquid biopsy. Since interleukin-8 (IL-8) is a main actor in senescence, its ability to interact with ECFCs has been explored. However, expression of CXCR1 and CXCR2, the two cellular receptors for IL-8, by ECFCs remain controversial as several teams published contradictory reports. Using complementary technical approaches, we have investigated the presence of these receptors on ECFCs isolated from cord blood. First, CXCR1 and CXCR2 were not detected on several clones of cord blood- endothelial colony-forming cell using different antibodies available, in contrast to well-known positive cells. We then compared the RT-PCR primers used in different papers to search for the presence of CXCR1 and CXCR2 mRNA and found that several primer pairs used could lead to non-specific DNA amplification. Last, we confirmed those results by RNA sequencing. CXCR1 and CXCR2 were not detected in ECFCs in contrary to human-induced pluripotent stem cell-derived endothelial cells (h-iECs). In conclusion, using three different approaches, we confirmed that CXCR1 and CXCR2 were not expressed at mRNA or protein level by ECFCs. Thus, IL-8 secretion by ECFCs, its effects in angiogenesis and their involvement in senescent process need to be reanalyzed according to this absence of CXCR-1 and - 2 in ECFCs.Graphical Abstract.Suspected unnatural or unexpected deaths in the Northern Territory of Australia are reportable to the coroner, and investigation of such cases typically includes a post-mortem examination with comprehensive toxicological screening. An autopsy case series of five Cumyl-PEGACLONE-related fatalities over a recent eighteen-month period is presented. Databases of the Northern Territory coroner's office and the Royal Darwin Hospital Forensic Pathology Unit were searched to identify deaths related to synthetic cannabis use between July 1, 2018 and December 31, 2020. Toxicological analysis was performed at Forensic Science South Australia using a combination of liquid chromatography, gas chromatography and mass spectrometry. Cumyl-PEGACLONE, a synthetic cannabinoid receptor agonist (SCRA) with a gamma-carbolinone core, was detected in five cases (range in post-mortem blood 0.73-3.0 μg/L). Concurrent alcohol use and underlying cardiovascular disease were considered relevant factors in most cases. Toxicological Significance Scoring was carefully considered in all five cases, and in four cases, the presence of Cumyl-PEGACLONE was considered to be highly significant (TSS = 3). Synthetic cannabis use has not previously been identified in Northern Territory drug trends, and only one fatality related to the use of gamma-carbolines was identified in a recent Australia-wide study on synthetic cannabinoid-related fatalities. Deaths related to Cumyl-PEGACLONE use are emerging in the Northern Territory of Australia; this has public health implications. Although learn more (s) of death related to Cumyl-PEGACLONE are not fully established, this additional descriptive case series reaffirm an association with underlying cardiovascular disease, and suggest that concurrent use with alcohol may be relevant.Traumatic optic neuropathy (TON) is characterized by visual dysfunction after indirect or direct injury to the optic nerve following blunt head trauma. TON is associated with increased oxidative stress and inflammation resulting in retinal ganglion cell (RGC) death. Remote ischemic post-conditioning (RIC) has been shown to enhance endogenous protective mechanisms in diverse disease models including stroke, vascular cognitive impairment (VCI), retinal injury and optic nerve injury. However, the protective mechanisms underlying the improvement of retinal function and RGC survival after RIC treatment remain unclear. Here, we hypothesized that RIC therapy may be protective following TON by preventing RGC death, oxidative insult and inflammation in the mouse retina. To carry out the study, mice were divided in three different groups (Control, TON and TON + RIC). We harvested retinal tissue 5 days after TON induction for western blotting and histochemical analysis. We observed increased TON-induced retinal cell deaoxidative stress and inflammation, and improves BRB integrity.
To evaluate the relationship of circulating immune cells with recurrence and metabolic/lifestyle factors in patients with early-stage breast cancer.
Patients with early-stage breast cancer were identified from the electronic record and institutional registry. Lymphocyte and monocyte counts were obtained from blood samples at time of diagnosis prior to any chemotherapy. #link# Correlations between lymphocyte and monocyte and recurrence were assessed in the entire cohort and among obese patients, those reporting alcohol consumption and smoking. Competing risk regression was used to analyze time to recurrence.
A total of 950 patients with ≥ 5years of follow-up were identified; 433 had complete data and were eligible for analysis. 293 (68%) had hormone receptor-positive breast cancer, 82 (19%) HER2 positive, and 53 (13%) triple negative. Patients in the highest quintile of lymphocytes compared to the lowest quintile had lower risk of recurrence (subhazard ratio (SHR) = 0.17, 95% CI [0.03-0.93], p = 0.041) while patients in the highest quintile of monocytes had lower risk for recurrence (SHR = 0.19, 95% CI [0.04, 0.92], p = 0.039). Higher monocytes were more strongly associated with lower recurrence among those reporting alcohol consumption (HR = 0.10, 95% CI [0.01, 0.91], p = 0.04). In obese patients, higher lymphocytes were associated with lower risk of recurrence (p = 0.046); in non-obese patients, higher monocytes were associated with lower risk of recurrence (p = 0.02). There were no correlations among patients who reported tobacco use.
High lymphocyte and monocyte counts are associated with lower recurrence rate in early-stage breast cancer, particularly in obese patients and those reporting alcohol consumption.
High lymphocyte and monocyte counts are associated with lower recurrence rate in early-stage breast cancer, particularly in obese patients and those reporting alcohol consumption.