Receptor-binding affinity and larvicidal activity of tetrahydroquinoline-type ecdysone agonists against Aedes albopictus

Tetrahydroquinolines (THQs), a class of nonsteroidal ecdysone agonists, are good candidates for novel mosquito control agents because they specifically bind to mosquito ecdysone receptors (EcRs). We have recently performed quantitative structure–activity relationship (QSAR) analyses of THQs to elucidate the physicochemical properties important for the ligand–receptor interaction. Based on previous QSAR results, here, we newly synthesized 15 THQ analogs with a heteroaryl group at the acyl moiety and evaluated their binding affinity against Aedes albopictus EcRs. We also measured the larvicidal activity of the combined set of previously and newly synthesized compounds against A. albopictus to examine the contribution of receptor-binding to larvicidal activity. Multiple regression analyses showed that the binding affinity and the molecular hydrophobicity of THQs are the key determinants of their larvicidal activity

Undernutrition Scored Using the CONUT Score with Hypoglycemic Status in ICU-Admitted Elderly Patients with Sepsis Shows Increased ICU Mortality

This study aimed to clarify whether the influence of undernutrition status and the degree of glycemic disorders affected the prognosis of patients with sepsis. A total of 307 adult patients with sepsis were retrospectively enrolled and analyzed. Characteristics, including nutrition status, calculated according to the Controlling Nutritional Status (CONUT) score of survivors and non-survivors, were examined. The independent prognostic factors of these patients with sepsis were extracted using multivariable logistic regression analysis. The CONUT scores in three glycemic categories were compared. Most patients with sepsis (94.8%) in the study had an undernutrition status according to their CONUT scores. High CONUT scores (odds ratio, 1.214; p = 0.002), indicating a poor nutritional status, were associated with high mortality. The CONUT scores in the hypoglycemic group were significantly higher than those in other groups with an undernutrition status (vs. hyperglycemic, p p = 0.006). The undernutrition statuses of patients with sepsis in the study scored using the CONUT were independent predictors of prognostic factors

Effects of human amnion-derived mesenchymal stromal cell transplantation in rats with radiation proctitis

Background aims. Mesenchymal stromal cells (MSCs) have been reported to be a promising cell source in cell therapy, and large amounts of MSCs can easily be isolated from human amnion. Therapeutic irradiation for intra-pelvic cancer often causes radiation proctitis; however, there is currently no effective treatment. We therefore investigated the effect of transplantation of human amnion derived MSCs (AMSCs) in rats with radiation proctitis. Methods. Amnion was obtained at cesarean delivery, and AMSCs were isolated and expanded. Sprague-Dawley rats were gamma-irradiated (5 Gy/d) at the rectum for 5 days. On day 5, AMSCs (1 x 10(6) cells) were intravenously transplanted. Rats were killed on day 8. Histological analyses were performed, and messenger RNA expression of inflammatory mediators was measured. In vitro, after gamma-irradiation of rat intestinal epithelial cells (IEC-6), the cells were cultured with AMSC-conditioned medium (CM). The effect of AMSC-CM was evaluated by measurement of caspase-3/7 activity, p53 transcription activity and quantitative reverse-transcription polymerase chain reaction for p53-target genes. Results. Histological examination demonstrated that epithelial injury and infiltration of inflammatory cells in the rectum were significantly suppressed by transplantation of AMSCs. In vitro, the cell injury in IEC-6 cells induced by gamma-irradiation was inhibited by AMSC-CM, which also inhibited the upregulation of p53 transcription activity, caspase-3/7 activity and p21 expression. Conclusions. Transplantation of AMSCs improved radiation proctitis, possibly through inhibition of cell injury and inflammatory reactions. AMSC transplantation should be considered as a new treatment for radiation proctitis

The role of medial prefrontal corticosterone and dopamine in the antidepressant-like effect of exercise

Despite the well-documented beneficial effect of exercise on stress coping and depression treatment, its underlying neurobiological mechanism remains unclear. This is further complicated by a 'side effect' of exercise: it increases basal glucocorticoid (CURT), the stress hormone, which has been shown to be a mediator linking stress to depressive disorders. Here we show that three weeks of voluntary wheel running reduced rats' immobility in the forced swim test (FST), an antidepressant-like effect. Monitoring extracellular fluids in the medial prefrontal cortex PFC (mPFC) using microdialysis we found that, wheel running was associated with higher baseline CORT, but lower FST-responsive CORT. Further, wheel running resulted in a higher dopamine (DA) both at baseline and following FST. Interestingly, the antidepressant-like effect of wheel running was completely abolished by intra-mPFC pre-microinjection of a D2R (haloperidol) but not D1R (SCH23390) antagonist, at a dose that does not affect normal rats' performance in the FST. It suggests that exercise exerts antidepressant-like effect through upregulated DA and in a D2R dependent way in the mPFC. Importantly, the antidepressant-like effect of wheel running was also abolished by intra-mPFC pre-microinjection of a GR antagonist (RU486). Finally, intra-mPFC pre-microinjection of RU486 also downregulated the originally elevated basal and FST-responsive DA in the mPFC of exercise rats. These results suggest a causal pathway linking CURT, GR, DA, and D2R, to the antidepressant-like effect of exercise. In conclusion, exercise achieves antidepressant-like effect through the CORT-GR-DA-D2R pathway and that the increased basal CORT by exercise itself may be beneficial rather than detrimental

Plasma fatty acid-binding protein 7 concentration correlates with depression/anxiety, cognition, and positive symptom in patients with schizophrenia

Because of the involvement of the brain in the pathophysiology of psychiatric disorders, obtaining information on the biochemical features that directly contribute to symptoms is challenging. The present study aimed to assess fatty acid-binding protein 7 (FABP7) expressed specifically in the brain and detectable in the peripheral blood and to investigate the correlation between blood FABP7 concentration and symptoms. We recruited 30, 29, and 35 patients with schizophrenia, bipolar disorder, and depression and evaluated using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAMD-21), respectively. Plasma FABP7 concentrations correlated with PANSS scores (R-2 = 0.3305, p < 0.001) but not with other scales. In the analysis of the relationship between five dimensions of schizophrenia symptoms derived from the PANSS 5-factor model and measured plasma FABP7 concentrations, severities of depression/ anxiety, cognition, and positive symptom were significantly correlated with plasma FABP7 concentrations. Further molecular investigation of the functional and kinetic analyses of FABP7 is necessary to understand the relationship of this protein with schizophrenia pathology. Nevertheless, the present study suggests that FABP7 can be a biological indicator reflecting the pathogenesis of schizophrenia and has potential applications as a biomarker for diagnosis and symptom assessment