Neuronal Nitric Oxide Synthase Regulates Depression-like Behaviors in Shortening-Induced Obese Mice.

Shortening is mainly derived from the partial hydrogenation of palm oil and widely used in fast food. Food processed with shortening contains high levels of industrial trans fatty acids. Studies have shown that there is a correlation between industrial trans fatty acids, obesity, and depression. However, the regulatory effect of neuronal nitric oxide synthase (nNOS) on depression in obese patients is still unknown. The purpose of this study was to explore mood changes in obese mice fed a high shortening diet, and to determine the regulatory effect of nNOS on depressive-like behaviors in obese mice. We used a high shortening diet-induced obesity mouse model to systematically assess the metabolic response, behavioral changes, prefrontal and hippocampal nNOS protein levels, and the effect of nNOS inhibitors (7-nitroindole) on depression-like behavior in obese mice. Interestingly, obese mice on a 9-week high-shortening diet developed short-term spatial working memory impairment and anxiety-like behavior, and obesity may be a risk factor for cognitive impairment and mood disorders. In animals fed a high shortening diet for 12 weeks, obese mice developed depression-like behavior and had significantly elevated levels of nNOS protein expression in the hippocampus and prefrontal lobe. Administration of the nNOS inhibitor 7-nitroindole could improve depression-like behaviors in obese mice, further suggesting that inhibition of nNOS is helpful for depression associated with obesity.

[Retrospective observation of curative effects on MDS refractory anemia with combination of all-trans retinoic acid, 1, 25-dihydroxyvitamin D3 and androgen].

This study was aimed to examine whether a combination of all-trans retinoic acid (ATRA), 1, 25-dihydroxyvitamin D(3) and androgen possesses the therapeutic value for the MDS-refractory anemia (MDS-RA), and to analyze the mechanisms in detail. 62 cases receiving a scheme of combination of ATRA, 1, 25-dihydroxyvitamin D(3) and androgen (group A) were monitored. The remaining 33 cases (group B) were provided with vitamin supplementation, chalybeate drugs, and one or two of the combination. Bone marrow aspiration and biopsy were performed for collecting the specimens at the baseline and afterwards. The conditions of the patients were monitored by means of weekly complete blood counts and the monthly examination, including toxicity test, physical examination, electrocardiography, and biochemistry panel. The results showed that after treating for 8 weeks in group A, 4 out of 62 patients showed complete remission and 12 patients showed partial remission according to the defined response criteria, and 43 patients (69.35%) showed hematological improvement (HI). The further treatment for 16 out of 62 patients (25.81%), 13 failures (10 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(5)) with a median survival interval of 26.25 months, were observed and interrupted for some reasons. However, partial remission was observed only in 3 patients in group B, and HI amounted to 51.51%. Furthermore, the disease progression was observed in 12 out of 33 patients (36.36%) with a median survival interval of 16 months, 9 failures (including 6 deaths, 2 RAEB and 1 RAEB-T) and 3 transformations (M(2), M(3), M(4)). The overall ratios of survival for 3 and 5 years in group A, which received the combination, reached to 69.24% and 53.72% respectively, in comparison with 52.23% and 31.34% in the patients of group B (log-rank, P = 0.016). The following requirements, if were met, would be significant for prognosis: the combination regiment, no transformation, children, no complication, female, 90-120 g/L of hemoglobin concentration, normal cellular bone marrow and uni-cytopenias (P < 0.05). Moreover, Cox regression showed that therapy, transformation and age are all the independent factors (P < 0.05). It is concluded that the combination of above mentioned 3 drugs may be effective and safe treatment for the patients with MDS-RA. Its relevant mechanisms can be involved in the combination, that elicits a wide range of pharmacological effects, such as differentiation, anti-tumor-promotion, anti-apoptosis, anti-angiogenesis, anti-cachexia and immunoregulation.