Effects of chronic exposure to a high fat diet, nutritive or non-nutritive sweeteners on hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes of male Sprague-Dawley rats.

PURPOSE: Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. METHODS: Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. RESULTS: All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. CONCLUSION: Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes.

Clinical outcomes of different regimens of intravitreal Conbercept for the treatment of choroidal neovascularization secondary to pathological myopia.

PURPOSE: To assess the clinical outcomes of two intravitreal injection regimens of Conbercept used to treat choroidal neovascularization secondary to pathological myopia (PM-CNV). METHODS: A total of 72 eyes of 72 patients were treated: 39 eyes received a single injection followed by treatment pro re nata (1 + PRN); 33 eyes first received 3 consecutive monthly injections (3 + PRN) then followed by PRN. After initial injection, patients were followed up for 12 months. RESULTS: The mean age of 72 patients was 45.3 ± 5.1 years, with the mean diopter of -10.62 ± 3.24D. The best corrected visual acuity (BCVA) was 0.86 ± 0.23 LogMAR with 1 + PRN and 0.90 ± 0.19 LogMAR with 3 + PRN at baseline (P = 0.422), 0.36 ± 0.07 and 0.33 ± 0.05 LogMAR at month 3 (P = 0.026); and 0.33 ± 0.03 and 0.32 ± 0.02 LogMAR at month 12 (P = 0.096). The central retinal thickness (CRT) was 333.5 ± 22.7 µm with 1 + PRN and 341.2 ± 20.9 µm with 3 + PRN at baseline (P = 0.139), 281.53 ± 10.28 and 273.15 ± 13.24 µm at month 3 (P = 0.004); 266.83 ± 8.14 and 264.91 ± 9.27 µm at month 12 (P = 0.350). The number of injections in the 1 + PRN group was significantly lower than that observed in the 3 + PRN group (2.15 ± 1.06 versus 3.36 ± 0.74; P < 0.001). During the follow-up, no serious ocular complications and adverse reactions related to Conbercept and injections occurred. CONCLUSIONS: Both injection regimens resulted in similar visual outcomes in PM-CNV patients. The 1 + PRN regimen had fewer injections and might be more suitable in this patient population.

Apigenin and baicalein ameliorate thoracic aortic structural deterioration and cognitive deficit via inhibiting AGEs/RAGE/NF-κB pathway in D-galactose-induced aging rats.

Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p-NF-κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process.

Diosmetin Ameliorates HFD-induced Cognitive Impairments via Inhibiting Metabolic Disorders, Mitochondrial Dysfunction and Neuroinflammation in Male SD Rats.

Currently, accumulating evidence has indicated that overnutrition-associated obesity may result in not only metabolic dysregulations, but also cognitive impairments. This study aimed to investigate the protective effects of Diosmetin, a bioflavonoid compound with multiple biological functions, on cognitive deficits induced by a high fat diet (HFD) and the potential mechanisms. In the present study, oral administration of Diosmetin (25, 50 and 100 mg/kg) for 12 weeks significantly reduced the body weight, restored glucose tolerance and normalized lipid profiles in the serum and liver in HFD-induced obese rats. Diosmetin also significantly ameliorated depression-like behaviors and impaired spatial memory in multiple behavioral tests, including the open field test, elevated plus-maze and Morris water maze, which was in accordance with the decreased pathological changes and neuronal damage in different regions of hippocampus as suggested by H&E and Nissl staining. Notably, our results also indicated that Diosmetin could significantly improve mitochondrial dysfunction induced by HFD through upregulating genes involved in mitochondrial biogenesis and dynamics, increasing mitochondrial ATP levels and inhibiting oxidative stress. Moreover, the levels of key enzymes involved in the TCA cycle were also significantly increased upon Diosmetin treatment. Meanwhile, Diosmetin inhibited HFD-induced microglial overactivation and down-regulated inflammatory cytokines both in the serum and hippocampus. In conclusion, these results indicated that Diosmetin might be a novel nutritional intervention to prevent the occurrence and development of obesity-associated cognitive dysfunction via metabolic regulation and anti-inflammation.