Obesity. 2006;14:1905-1913. Objective: Human adenovirus 36 (Ad-36) increases adiposity and reduces serum lipids in chicken, mouse, and nonhuman primate models, and it is linked to obesity in seroepidemiological studies in humans. Involvement of the central nervous system (CNS) or adipose tissue in the mechanism of Ad-36-induced adiposity is unknown. The effects of Ad-36 on adiposity and on the neuroendocrine system were investigated in a rat model. Research Methods and Procedures: Five-week-old male Wistar rats were inoculated intraperitoneally with Ad-36 or medium. Results: Despite similar food intakes, infected rats attained significantly greater body weight and fat pad weight by 30 weeks post-inoculation. Epididymal-inguinal, retroperitoneal, and visceral fat pad weights of the infected group were greater by 60%, 46%, and 86%, respectively (p Ͻ 0.00001). The fasting serum insulin level and homeostasis model assessment index indicated greater insulin sensitivity in the infected group. Visceral adipose tissue expression of glycerol 3-phosphate dehydrogenase, peroxisome proliferatoractivated receptor ␥, and CCAAT/enhancer-binding protein ␣ and ␤ was markedly increased in the infected animals compared with controls. Ad-36 decreased norepinephrine levels significantly in the paraventricular nucleus in infected vs. control rats (mean Ϯ standard error, 8.9 Ϯ 1.1 vs. 12.8 Ϯ 1.2 pg/g protein; p Ͻ 0.05). Ad-36 markedly decreased serum corticosterone in infected vs. control rats (mean Ϯ standard error, 97 Ϯ 41.0 vs. 221 Ϯ 111 ng/mL; p Ͻ 0.005). Discussion: The results suggest that the pro-adipogenic effect of Ad-36 may involve peripheral as well as central effects. The male Wistar rat is a good model for the elucidation of metabolic and molecular mechanisms of Ad-36-induced adiposity.

Garlic (Allium sativum) has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic's other physiological effects.

Background: Accumulating evidence has revealed that an increasing number of microRNAs (miRNAs) are dysregulated in papillary thyroid cancer (PTC) and that their dysregulation plays an important role in PTC onset and progression. Reportedly, miRNA-564 (miR-564) is downregulated in several types of human cancer. However, its expression profile and specific functions in PTC remain unclear to date. Methods: In this study, we used reverse transcription-quantitative polymerase chain reaction to detect miR-564 expression in PTC tissues and cell lines. Further, the regulatory roles of miR-564 in the malignant development of PTC in vitro and in vivo were examined using a series of functional experiments. In addition, the possible underlying mechanisms and signaling pathways involved were investigated. Results: We demonstrated that miR-564 expression markedly decreased in PTC tissues and cell lines, and this decrease correlated with the lymph node metastasis and tumor–node–metastasis stage. miR-564 upregulation significantly inhibited cell proliferation, migration, and invasion and induced cell apoptosis in vitro as well as hindered tumor growth in vivo. Furthermore, astrocyte-elevated gene-1 (AEG-1) was identified as a direct target gene of miR-564 in PTC cells. Its expression was upregulated and inversely correlated with miR-564 expression in clinically PTC tissues. Additionally, the silencing of AEG-1 expression could imitate the action of miR-564 overexpression in PTC cells. Remarkably, the restoration of AEG-1 expression partially abolished the tumor-suppressing effects induced by a miR-564 upregulation in PTC cells. Ectopic miR-564 expression deactivated the PTEN/Akt pathway in PTC cells in vitro and in vivo. Conclusion: Overall, the findings of the current study suggest that miR-564 is a tumor-suppressive miRNA that exerts crucial roles in the development and progression of PTC. Therefore, this miRNA might be a promising candidate target in the anticancer treatment of patients with PTC.

Purpose An increasing number of studies have documented that dysregulation of microRNAs (miRNAs) is common in glioblastoma multiforme (GBM). miR-652 is aberrantly expressed in various human cancers and plays important roles in numerous cancer-related processes. However, the expression profiles and potential roles of miR-652 in GBM remain largely unknown. Patients and methods Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine miR-652 expression in GBM tissues and cell lines. The effects of miR-652 upregulation on GBM cell proliferation, clone formation, apoptosis, migration and invasion were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clone formation, flow cytometry and Transwell ® migration and invasion assays, respectively. In vivo xenotransplantation was utilized to determine the effect of miR-652 on GBM tumor growth in vivo. Of note, the molecular mechanisms underlying the tumor-suppressing activity of miR-652 upregulation in GBM cells were also investigated using a series of experiments, including bioinformatics analysis, luciferase reporter assay, RT-qPCR and Western blot analysis. Results miR-652 expression was considerably downregulated in GBM tissues and cell lines. Low miR-652 expression was strongly correlated with Karnofsky performance score and tumor size. Overall survival duration was shorter in GBM patients with low miR-652 expression than in those with high miR-652 expression. miR-652 resumption considerably suppressed the proliferation, clone formation, migration, and invasion and promoted the apoptosis of GBM cells in vitro. In addition, forkhead-box k1 (FOXK1) was demonstrated as the direct target gene of miR-652 in GBM cells. FOXK1 downregulation led to a tumor-suppressing activity similar to that of miR-652 upregulation. Restoration of FOXK1 expression partially neutralized the influence of miR-652 overexpression on GBM cells. Furthermore, ectopic miR-652 expression deactivated the AKT/mTOR pathway in GBM cells via FOXK1 regulation. Moreover, miR-652 impaired GBM tumor growth in vivo, probably caused by miR-652-mediated suppression of FOXK1/AKT/mTOR signaling. Conclusion miR-652 inhibits FOXK1 and deactivates the AKT/mTOR pathway, thereby resulting in the suppression of malignant phenotypes of GBM cells in vitro and in vivo.