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Intestinal barrier integrity in patients with plaque psoriasis

Posted by M Sikora, C Maciejewski, L Rudnicka, et al. on 2018-10-23 23:14:26


Psoriasis is a chronic inflammatory systemic disease. Growing evidence suggests that human homeostasis depends on a mutualistic relationship with gut bacteria that produce a number of biologically active compounds. Therefore, enteric microbiota dysbiosis with gut barrier disruption may be an important factor in the development of chronic inflammatory diseases. The aim of our study was to assess non‐invasive markers of intestinal barrier integrity in patients with moderate to severe psoriasis. Concentrations of claudin‐3 (intestinal epithelial tight junction structure) and intestinal fatty acid binding protein (I‐FABP; marker of enterocyte damage) were determined in the blood of patients with chronic plaque psoriasis (n = 20) and healthy individuals (n = 20) using commercially available enzyme‐linked immunoassay test kits. Claudin‐3 concentration was higher in patients with psoriasis compared with healthy control (median, 54.07 vs 42.36 ng/mL; P < 0.001). Patients with psoriasis also had elevated concentration of plasma I‐FABP (median, 708.8 vs 147.1 pg/mL; P < 0.05). Our results support the hypothesis that dysfunction of the intestinal barrier in psoriasis disturbs the homeostatic equilibrium between the microbiota and immune system. Further studies are needed in order to develop new therapeutic interventions based on modulation of intestinal permeability.


Aldrin, dieldrin, and DDT are chlorinated insecticides that are unintentionally widespread in the environment. It was previously shown that all of the aforementioned compounds increased secretion of ovarian oxytocin (OT), which is a potent uterotonic agent. However, only DDT and its metabolite (DDE) promoted, while aldrin and dieldrin inhibited basal and OT-stimulated myometrial contractions in cows. Therefore, the aim of this study was to determine the effect of these treatments on the reception and further transmission of the OT-signal for myometrial contractions and on the levels of contractile-associated integral proteins (caveolin; CAV) and gap junction proteins (GAPs). Moreover, their effect on reception of signal for the relaxation of myometrium was also studied. Myometrial strips or cells from non-pregnant (8–12 days of oestrous cycle) or late pregnant (5–8 months) cows were incubated with the studied compounds at environmentally relevant dose (10?ng/ml), which was chosen according to the previous studies. DDT and DDE increased the CAV protein level, while dieldrin decreased the GAPs level. None of the studied compounds affected mRNA expression of the OT receptor and expression of the second messengers (DAG, IP3, PKC, MLCK). Oppositely, DDE and dieldrin decreased mRNA expression of the relaxin (RLX) receptor. Changes in the amount of contractile-associated integral proteins may be involved in the molecular mechanism underlying the adverse effects of the studied insecticides on myometrial motility. Admittedly, none of the studied compounds impaired the reception or further intracellular transmission of the OT signal to promote contractions during the oestrous cycle, while they showed potential to impair the transmission the signal between cells as well as to diminish the effects of one of the primary inhibitor (RLX) of myometrial contractions during gestation.

Relationship of muscle function to circulating myostatin, follistatin and GDF11 in older women and men

Posted by E Fife, J Kostka, A Guligowska, et al. on 2018-09-28 19:40:58



Myostatin, its inhibitor follistatin, and growth/differentiation factor 11 (GDF11) have been proposed as factors that could potentially modify biological aging. The study aimed to test whether there is a relationship between these plasma circulating proteins and muscle strength, power and optimal shortening velocity (υopt) of older adults.


The cross-sectional study included 56 women and 45 men aged 60 years and older. Every participant underwent examination which included anthropometric and bioimpedance analysis measurements, functional and cognitive performance tests, muscle strength of upper and lower extremities, muscle power testing with two different methods and blood analyses.


Women had higher plasma levels of myostatin and GDF11 than men. Men had higher plasma level of follistatin than women. In women, plasma level of myostatin was negatively correlated with left handgrip strength and υopt. Follistatin was negatively correlated with maximum power output (Pmax), power relative to kg of body mass (Pmax?kg− 1) (friction-loaded cycle ergometer) and power at 70% of the 1-repetition maximum (1RM) strength value (P70%) of leg press (Keiser pneumatic resistance training equipment), and positively correlated with the Timed Up & Go (TUG) test. GDF11 was negatively correlated with body mass, body mass index, waist circumference, fat mass and the percentage of body fat. In men, there were no significant correlations observed between circulating plasma proteins and muscle function measures.


The circulating plasma myostatin and follistatin are negatively associated with muscle function in older women. There is stronger relationship between these proteins and muscle power than muscle strength. GDF11 has a higher association with the body mass and composition than muscle function in older women.


Montelukast (MK),a cysteinyl leukotriene (CysLT1) receptor antagonist, latterly exhibited a remarkable neuroprotective activity in various neurodegenerative disorders. This study aims to elucidate the neuroprotective effect of MK in rotenone-induced Parkinson disease(PD) model in rats. Ninety six male rats were split into four groups: vehicle control (0.2?ml/kg/48?h, sc), MK (10?mg/kg/day, ip), rotenone (1.5?mg/kg/48?h, sc.) and rotenone pretreated with MK. Rotenone treatment led to significant reduction in motor functioning and elevation in oxidative stress markers. Additionally, upregulation of p38 mitogen-activated protein kinase (p38 MAPK) and CysLT1 receptor expressions were anchored with enhanced striatal microglial activation generating a severe neuro-inflammatory milieu. Furthermore, an augmentation in p53 expression and cleaved caspases-3 activity increased apoptotic neurodegeneration synchronized with reduction of striatal tyrosine hydroxylase (TH) content. Changes in neuronal morphology was also noted. MK administration significantly mitigated motor impairment and rise in oxidative stress mediators. As well, the anti-inflammatory activity of MK was manifested by hindering the principal controller of inflammatory pathway, nuclear factor-kappa B, followed by its downstream pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta), by attenuating striatal microglial activation and hampering the expression of both p38 MAPK and CysLT1. Moreover, MK revealed a decline in p53 expression with its downstream cleaved caspases-3 which resulted in preservation of striatal TH terminals as verified by increased striatal TH content and improvement in the histopathological changes incited by rotenone. In conclusion, MK endowed neuroprotective effects in rotenone-induced PD animal model via attenuation of microglial cell activation and p38 MAPK expression.


This work evaluated the effects of moderate physical exercise performed under hypoxic conditions on melatonin and sleep. Forty healthy men were randomized into four groups: Normoxia (N) (n=10); Hypoxia (H) (n=10); Exercise under Normoxia (EN) (n=10); and Exercise under Hypoxia (EH) (n=10). The observation period for all groups was approximately 36h, beginning with a first night devoid of any intervention. Aerobic exercise was performed by the EN and EH groups on a treadmill at 50% of the ventilatory threshold intensity for 60?min. Sleep evaluation was performed on the 1st and 2nd nights. Venous blood samples for the melatonin measurement were obtained on the 1st and 2nd days at 7:30 AM as well as on the 1st and 2nd nights at 10:30 PM. On the 2nd night, melatonin was higher in the H group than in the N group, but both were lower than values of the EH group. The nocturnal increase in melatonin was inversely correlated with the oxygen saturation of hemoglobin (SaO2%) on the 2nd night in the H group and on the 2nd day in the EH group. Diurnal remission of nocturnal melatonin appeared to be postponed in the H group and even more so in the EH group. Thus, normobaric hypoxia, which is equivalent to oxygen availability at an altitude of 4500 m, acutely increases melatonin. Moreover, diurnal remission of the nocturnal increase in melatonin seems to be delayed by hypoxia alone but even more so when acting together with exercise.

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