Aggerholmwinters9147
Our study aimed to investigate circulating CD8
T cell subpopulations and pro-inflammatory cytokines in the neuromyelitis optica spectrum disorder (NMOSD).
A total of 121 peripheral blood samples were obtained from 57 patients with NMOSD, 34 patients with multiple sclerosis (MS), and 30 sex- and age-matched healthy controls (HCs) for detection of CD8
T cell subpopulations, including phenotypes of naïve (T
, CD62L
CD45RO
), effector/memory (T
, CD62L
CD45RO
), memory precursor (T
, CD127
KLRG1
), and short lived effector (T
, CD127
KLRG1
). In addition, 36 samples from 18 NMOSD, 12 MS, and 6 sex- and age-matched HCs for detecting pro-inflammatory cytokines (IFNγ and TNFα) using flow cytometry.
Compared with HCs, we found significantly reduced CD8
T
and increased CD8
T
in both NMOSD and MS，while decreased CD8
T
was only observed in NMOSD. Patients treated with immunotherapy were associated with increased CD8
T
and decreased CD8
T
in NMOSD. Moreover NMOSD cohort showed significant higher proportions of IFNγ
CD8
T cells and proportions of TNFα
CD8
T cells than HC and MS cohorts. On the contrary, obviously decreased IFNγ and TNFα were found in NMOSD patients treated with immunotherapy. Furthermore, Multivariate linear regression analyses revealed that age was negatively correlated with CD8
T
and T
, and positively associated with T
; however, sex, EDSS scores and disease phase were not significantly associated with CD8
T subpopulations.
This current study provides an evidence that circulating CD8
T cell with abnormal subpopulations and increased pro-inflammatory were associated with pathogenesis of autoimmune demyelinating disease of CNS, especially in NMOSD.
This current study provides an evidence that circulating CD8+ T cell with abnormal subpopulations and increased pro-inflammatory were associated with pathogenesis of autoimmune demyelinating disease of CNS, especially in NMOSD.
Trauma-induced coagulopathy has been extensively investigated in the multitrauma setting, but only sparsely following moderate orthopedic trauma. The purpose of this study was to evaluate changes in the hemostatic profile of patients with hip fractures, using rotational thromboelastometry (ROTEM).
198 patients with hip fractures who underwent surgery were included in the study. A matched group of 52 healthy individuals was also enrolled. Demographics, conventional laboratory assays, and ROTEM parameters were recorded and compared between patients and healthy adults. The preoperative and postoperative ROTEM values of fractured patients were also compared.
The conventional coagulation assays were similar for the 2 groups. However, several ROTEM parameters including EXTEM MCF (P<.001), EXTEM alpha angle (P<.001), INTEM MCF (P<.001), INTEM A10 (P<.001), and INTEM alpha angle (P<.001) significantly differed between the 2 groups indicating a higher coagulation potential following hip fractures. Also, fractured patients had significantly lower INTEM and EXTEM CT values (P=.008 and P=.012, respectively) and significantly lower INTEM and EXTEM CFT values (P<.001). Adjusted analysis for confounders further confirmed the direct relationship between hip fracture and higher coagulation activity. Last, INTEM CT and CFT significantly decreased (P=.008 and P<.001, respectively), while INTEM MCF, A10, and alpha angle significantly increased (P<.001) postoperatively, indicating that surgery further increases the coagulation potential.
A higher coagulation activity following hip fractures and surgical treatment can be detected by ROTEM shortly after the injury, even when this is undetectable by conventional coagulation assays.
A higher coagulation activity following hip fractures and surgical treatment can be detected by ROTEM shortly after the injury, even when this is undetectable by conventional coagulation assays.The mechanisms underlying the association between orthostatic hypotension (OH) and cardiovascular disease are unclear. We investigated whether OH is associated with circulating cardiovascular risk markers. This was a cross-sectional analysis of 3857 older, community-dwelling men. "Consensus OH" was defined as a sitting-to-standing decrease in systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg that occurred within three minutes of standing. Multiple generalized linear regression and logistic models were used to examine the association between cardiovascular risk markers and OH. Consensus OH was present in 20.2%, consisting of isolated systolic OH in 12.6%, isolated diastolic OH in 4.6%, and combined systolic and diastolic OH in 3.0%. Concentration of von Willebrand factor, a marker of endothelial dysfunction, was positively associated with isolated systolic OH (OR 1.35, 95% CI 1.05-1.73) and combined systolic and diastolic OH (OR 2.27, 95% CI 1.35-3.83); high circulating phosphate concentration, which may reflect vascular calcification, was associated with isolated diastolic OH (OR 1.53, 95% CI 1.04-2.25) and combined systolic and diastolic OH (OR 2.12, 95% CI 1.31-3.44), high-sensitivity troponin T, a marker of myocardial injury, was positively associated with isolated diastolic OH (OR 1.69, 95% CI 1.07-2.65) and N-terminal pro-brain natriuretic peptide, a marker of cardiac stress, was positively associated with combined systolic and diastolic OH (OR 2.14, 95% CI 1.14-4.03). In conclusion, OH is associated with some cardiovascular risk markers implicated in endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress. Clinicians should consider assessing cardiovascular risk in patients with OH.Endothelial progenitor cells (EPCs) promote the maintenance of the endothelium by secreting vasoreparative factors. A population of EPCs known as early outgrowth cells (EOCs) is being investigated as novel cell-based therapies for the treatment of cardiovascular disease. We previously demonstrated that the absence of liver X receptors (LXRs) is detrimental to the formation and function of EOCs under hypercholesterolemic conditions. Here, we investigate whether LXR activation in EOCs is beneficial for the treatment of atherosclerosis. EOCs were differentiated from the bone marrow of wild-type (WT) and LXR-knockout (Lxrαβ-/-) mice in the presence of vehicle or LXR agonist (GW3965). WT EOCs treated with GW3965 throughout differentiation showed reduced mRNA expression of endothelial lineage markers (Cd144, Vegfr2) compared with WT vehicle and Lxrαβ-/- EOCs. GW3965-treated EOCs produced secreted factors that reduced monocyte adhesion to activated endothelial cells in culture. When injected into atherosclerosis-prone Ldlr-/- mice, GW3965-treated EOCs, or their corresponding conditioned media (CM) were both able to reduce aortic sinus plaque burden compared with controls. Furthermore, when human EOCs (obtained from patients with established CAD) were treated with GW3965 and the CM applied to endothelial cells, monocyte adhesion was decreased, indicating that our results in mice could be translated to patients. Ex vivo LXR agonist treatment of EOCs therefore produces a secretome that decreases early atherosclerosis in Ldlr-/- mice, and additionally, CM from human EOCs significantly inhibits monocyte to endothelial adhesion. Thus, active factor(s) within the GW3965-treated EOC secretome may have the potential to be useful for the treatment of atherosclerosis.
Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI®), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged≥2months in the United States, and is currently under Health Authority review in the EU.
Subjects included patients with SMA aged 2months-60years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. Ophthalmologic assessments, including functional assessments (age-appropriate visual acuity and visual field) and imaging (spectral domain optical coherence tomography [SD-OCT], fundus photography, and fundus autofluorescence [FAF]), were conducted at baseline and every 2-6months depending on study and assessment. SD-OCT, FAF, fundus photography, and threshold perimetry were evaluated by an independent, masked reading center. Adverse events (AEs) were reported throughout these. These results suggest that safety ophthalmologic monitoring is not needed in patients receiving risdiplam, as also reflected in the United States Prescribing Information for risdiplam.
Periplocin is a monomeric compound that exhibits anti-tumor activities. It is extracted from Cortex Periplocae.
This study aimed at determining the effect of periplocin treatment on the apoptosis and proliferation of human pancreatic cancer cells, and to elucidate on its mechanisms of action.
PANC1 and cfpac1 cells were treated with periplocin. Cell proliferation was detected by RTCA, Ki67 immunofluorescence, and a clonogenic assay. The transwell assay was used to examine cell migration and invasion functions. The expression of apoptosis-associated proteins was detected by flow cytometry and western blotting. Total RNA was extracted from the treated and untreated group of PANC1 cells for RNA-seq detection and analysis. Differentially expressed genes were screened for GO biological process and KEGG pathway analysis. Finally, CFPAC1 cells were subcutaneously inoculated into BALB / c nude mice to assess tumor growth.
Periplocin inhibited the proliferation of PANC1 and CFPAC1 cells and induced their apoptosis by activating the AMPK/mTOR pathway and inhibiting p70 S6K. It also attenuated the cell migration, invasion, and inhibited the growth of cfpac1 xenografts in nude mice.
Periplocin inhibits human pancreatic cancer cell proliferation and induces their apoptosis by activating the AMPK / mTOR pathway.
Periplocin inhibits human pancreatic cancer cell proliferation and induces their apoptosis by activating the AMPK / mTOR pathway.Our previous study on rat skin showed that cumulative oxidative pressure induces profound structural and ultrastructural alterations in both rat skin epidermis and dermis during aging. Here, we aimed to investigate the biophotonic properties of collagen as a main dermal component in the function of chronological aging. We used second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) on 5 μm thick skin paraffin sections from 15-day-, 1-month- and 21-month-old rats, respectively, to analyze collagen alterations, in comparison to conventional light and electron microscopy methods. Obtained results show that polarization-resolved SHG (PSHG) images can detect collagen fiber alterations in line with chronological aging and that this method is consistent with light and electron microscopy. Moreover, the β coefficient calculated from PSHG images points out that delicate alterations lead to a more ordered structure of collagen molecules due to oxidative damage. The results of this study also open the possibility of successfully applying this fast and label-free method to previously fixed samples.
