Hanleypearce4946
Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe coronavirus disease 2019 (COVID-19). Recently, early clinical data reported the feasibility of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown.
Here, we used airways-instilled lipopolysaccharide (LPS) and influenza virus (H1N1) as murine models of pneumonia, and toll-like receptor (TLR)-3 stimulation in human lung macrophages.
Low doses of RT (0.5-1 Gray) decreased LPS-induced pneumonia, and increased the percentage of nerve- and airway-associated macrophages producing interleukin (IL) 10. During H1N1 viral infection, we observed decreased lung tissue damage and immune cell infiltration in irradiated animals. Low doses of RT increased IL-10 production by infiltrating immune cells into the lung. Irradiation of TLR-3 ligand-stimulated human lung macrophages ex vivo increased IL-10 secretion and decreased interferon γ production in the culture supernatant. The percentage of human lung macrophages producing IL-6 was also decreased.
Our data highlight a mechanism by which low doses of RT regulate lung inflammation and skew lung macrophages toward an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses of RT, such as COVID-19-induced ARDS.
Our data highlight a mechanism by which low doses of RT regulate lung inflammation and skew lung macrophages toward an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses of RT, such as COVID-19-induced ARDS.
As the association between insulin resistance and ischaemic stroke is conflicting, our study aimed to examine the association between triglyceride-glucose (TyG), a surrogate marker of insulin resistance, and incident ischaemic stroke, and also to further assess the potential effect of modification by several known risk factors of stroke.
The Rural Chinese Cohort Study enrolled 11,777 participants, aged ≥40 years, who were free of stroke and cardiovascular disease at baseline during 2007-2008, and who were then followed during 2013-2014. TyG was determined using the following formula Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The relative risk (RR) and 95% confidence interval (CI) of incident ischaemic stroke associated with TyG were estimated using modified Poisson regression models.
During a median follow-up duration of 6 years, 677 new ischaemic stroke cases were identified. After multivariate adjustment, RR (95% CI) values for ischaemic stroke were 1.33 (1.01-1.75), 1.57 (1.17-2.10) and 1.95 (1.34-2.82) in TyG quartile (Q) 2, 3 and 4 groups, respectively, compared with Q1. CB-5083 A significant interaction between TyG index and age for risk of ischaemic stroke (P
< 0.001) was also observed. However, no significant interaction was found between TyG index and other potential risk factors of risk for ischaemic stroke, although there were significant positive associations with female, non-smoker, non-drinker, low or moderate physical activity, non-obese and non-type 2 diabetes mellitus groups.
Elevated TyG index is an independent predictor of ischaemic stroke in the general population, and insulin resistance may be positively associated with future stroke risk.
Elevated TyG index is an independent predictor of ischaemic stroke in the general population, and insulin resistance may be positively associated with future stroke risk.
Type A personality-characterized by time urgency, strong drive, and a need for achievement and competitiveness-has been shown to be associated with reduced mortality in patients with diabetes. However, it is not known whether a Type A personality might protect against diabetic foot ulcer (DFU). This prompted our present analysis of the association between Type A personality and DFU.
The Bortner Scale questionnaire was used to assess Type A personality in 386 patients with type 2 diabetes (T2D), including 104 patients also presenting with, and 282 presenting without, DFU. Additional questionnaires were used to assess perceived stress and depression.
Type A Bortner scores were significantly lower in T2D patients with vs without DFU (166.64 ± 38.76 vs 178.79 ± 36.61, respectively; P = 0.005). In patients with DFU, the prevalence of Type A personality traits was significantly lower than in those without DFU (48% vs 64.5%, respectively; P = 0.005) whereas, in contrast, Type B personality traits (the opposite, might favour the development of DFU.The zebrafish (Danio rerio) has been considered a suitable model organism to assess the evolutionarily conserved bases of behavioral and neuroendocrine responses to stress. Depending on the nature of the stressor, prolonged stress may elicit habituation or evoke long-term changes in the central nervous systems (CNS) often associated with various neuropsychiatric disorders. Conspecific alarm substance (CAS) and net chasing (NC) constitute chemical and physical stressors, respectively, which cause aversive behaviors and physiological changes in fishes. Here, we investigate whether predictable chronic stress (PCS) using two homotypic stressors differently modulates behavioral and physiological responses in zebrafish. PCS-CAS or PCS-NC were performed for 14 days, 2-times daily, while locomotion, exploratory activity, anxiety-like behaviors, and whole-body cortisol levels were measured on day 15. PCS-CAS reduced distance traveled, the number of transitions and time in top area, as well as increased the latency to enter the top in the novel tank test. In the light/dark test, CAS-exposed fish showed decreased time spent in lit area, shorter latency to enter the dark area, and increased risk assessments. PCS-CAS also increased whole-body cortisol levels in zebrafish. Although PCS-NC reduced the latency to enter the dark area, whole-body cortisol levels did not change. Moreover, acute experiments revealed that both CAS and NC promoted anxiogenesis and increased cortisol levels, suggesting habituation to stress following PCS-NC. Overall, our novel findings demonstrate that PCS induces behavioral and physiological changes in zebrafish depending on the nature of the stressor.