SNHG8 promotes cell proliferation, migration, and invasion of nasopharyngeal carcinoma cells as an oncogene through miR-588/HMGA2 axis.

Nasopharyngeal carcinoma (NC) poses a threat to the life of patients. Long non-coding RNA (LncRNA) is a novel kind of non-coding RNA, which plays a pivotal role through sponge microRNA (miRNA). Abnormal expression of small nucleolar RNA host gene 8 (SNHG8) is involved in various tumors; however, the role of SNHG8 in NC remains unknown. Quantitative real-time PCR (qRT-PCR) and Western blotting was employed to detect the expression levels of SNHG8, miR-588, and high mobility group A2 (HMGA2). Cell proliferation, migration, and invasion were analyzed by CCK-8 and transwell assays. miR-588 binding sites in SNHG8 were predicted by LncBase analysis. Luciferase reporter and RNA pull-down assay were used to confirm the interaction of SNHG8 and miR-588. SNHG8 was highly expressed in NC cells. The prognosis of the patients with NC in the high expression levels of SNHG8 was poorer than that in the low expression levels. The expression of SNHG8 was closely related to tumor size, TNM stage, and distal metastasis. Knockdown of SNHG8 inhibited cell proliferation, migration, and invasion of NC. SNHG8 targeted miR-588. Inhibition of miR-588 could partially reverse the knockdown of SNHG8 in NC cells, and miR-588 targeted HMGA2. In conclusion, SNHG8 promotes proliferation, migration, and invasion of NC cells through miR-588/HMGA2 in NC as an oncogene.

Effect of Bayesian penalty likelihood algorithm on 18F-FDG PET/CT image of lymphoma.

OBJECTIVE: Recently, a new Bayesian penalty likelihood (BPL) reconstruction algorithm has been applied in PET, which is expected to provide better image resolution than the widely used ordered subset expectation maximization (OSEM). The purpose of this study is to compare the differences between these two algorithms in terms of image quality and effects on clinical diagnostics and quantification of lymphoma. METHODS: A total of 246 FDG-positive lesions in 70 patients with lymphoma were retrospectively analyzed by using BPL and OSEM + time-of-flight + point spread function algorithms. Visual analysis was used to evaluate the effects of different reconstruction algorithms on clinical image quality and diagnostic certainty. Quantitative analysis was used to compare the differences between pathology and lesion size. RESULTS: There were significant differences in lesion-related SUVmax, total-lesion-glycolysis (TLG), and signal-to-background ratio (SBR) (P < 0.01). The variation Δ SUVmax% and Δ SBR% caused by the two reconstruction algorithms were negatively correlated with tumor diameter, while Δ MTV% and Δ TLG% were positively correlated with tumor diameter. In the grouped analysis based on pathology, there were significant differences in lesion SUVmax, lesion SUVmean, and SBR. In non-Hodgkin's lymphoma (diffuse large B cells and follicular lymphoma), diversities were significantly found in SUVmax, SUVmean, SBR, and TLG of the lesions (P < 0.05). According to the grouped analysis based on lesion size, for lesions smaller than 1 cm and 2 cm, there was a significant difference in SUVmean, SUVmax, SBR, and MTV, but not in lesions larger than or equal to 2 cm (P > 0.05), and the liver background SUVmean (P > 0.05) remained unchanged. CONCLUSION: BPL reconstruction algorithm could effectively improve clinical image quality and diagnostic certainty. In quantitative analysis, there were no significant differences among different pathological groups, but there were significant diversities in lesion sizes. Especially for small lesions, lesion SUVmax increased and SBR was significantly improved, which may better assist in the diagnosis of small lesions of lymphoma.

miR-188-3p Inhibits Vascular Smooth Muscle Cell Proliferation and Migration by Targeting Fibroblast Growth Factor 1 (FGF1).

BACKGROUND As one of the crucial causes leading to cardiovascular disease, atherosclerosis (AS) develops in association with the dysfunction of vascular smooth muscle cells (VSMCs). However, the associated mechanism of the proliferation and migration in VSMCs requires further elucidation. MATERIAL AND METHODS Human VSMCs and ApoE-knockout (ApoE-/-) mice were used to establish AS cell and animal models, respectively. Expression levels of miR-188-3p and fibroblast growth factor 1 (FGF1) mRNA were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was used to assess FGF1 protein expression. The proliferation, migration, and apoptosis of the cells were determined using MTT, BrdU, and Transwell assays, as well as flow cytometry analysis. The interaction between miR-188-3p and FGF1 was validated using dual-luciferase reporter gene assay, qRT-PCR, and Western blot analysis. RESULTS MiR-188-3p was found to be significantly decreased in the serum of AS patients and ApoE-/- mice as well as VSMCs of ApoE-/- mice and human VSMCs treated with oxidized low-density lipoprotein. MiR-188-3p repressed the proliferation and migration of VSMCs but promoted apoptosis of VSMCs. The binding site between miR-188-3p and 3' untranslated region (3'-UTR) of FGF1 was identified, and FGF1 was verified as a target gene of miR-188-3p. Restoration of FGF1 reversed the effects of miR-188-3p on VSMCs. CONCLUSIONS MiR-188-3p suppresses the proliferation and migration of VSMCs and induces their apoptosis through targeting FGF1.

(3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one inhibited osteosarcoma growth by inducing apoptosis.

As one of the leading causes of cancer-associated mortalities worldwide, the overall survival rate of osteosarcoma has stably remained at 15-30% for several decades. (3R)- 5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM), isolated from the whole plant of Selaginella moellendorffii Hieron., has been reported to have pharmacological activities. In the present study, the anti-proliferative effects of TIM against osteosarcoma were evaluated, and the underlying molecular mechanisms were explored. The results demonstrated that TIM inhibited proliferation and induced apoptosis in U2OS cells. Furthermore, the expression of the pro-apoptotic protein NOXA in the intrinsic apoptosis pathway was upregulated by TIM, while the expression of myeloid cell leukemia 1, an anti-apoptotic protein, was downregulated. In addition, TIM increased the protein expression of the endoplasmic reticulum stress markers inositol-requiring enzyme 1, activating transcription factor 6 and glucose-regulated protein 78. These results suggested that TIM induced ER stress response while activating intrinsic apoptosis. Furthermore, treating osteosarcoma tumor-bearing mice with TIM significantly inhibited the tumor growth in the xenograft animal model. Overall, the study results suggested that TIM may serve as a potential antitumor agent against osteosarcoma.

MiR-223 inhibitor suppresses proliferation and induces apoptosis of thyroid cancer cells by down-regulating aquaporin-1.

To investigate the effect of miR-223 on thyroid cancer cells, further to study its potential mechanisms. The difference in miR-223 expression between normal thyroid Nthy-ori3-l cells and thyroid cancer SW579 cells was detected by PCR. The miR-223 overexpression and silencing vector transfection were verified by qRT-PCR. To further investigate the role of miR-223 in AQP-1, the AQP-1 siRNA vector was transfected on the basis of transfection of miR-223 inhibitor vector. The cell proliferation was detected by plate cloning, MTT, and cellular immunofluorescence assays. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the expression of AQP-1 protein. The expression of miR-223 in SW579 cells was higher than that in normal cells. After transfection with miR-223 mimic, miR-223 expression was increased in SW579 cells. MiR-223 inhibitor transfection can inhibit SW579 cells proliferation, promote apoptosis, and inhibit cell cycle G0/G1 arrest. The SW579 cells proliferation was decreased, and the apoptosis rate was increased after transfection of AQP-1 silencing vector. Compared with the AQP-1 siRNA group, the SW579 cells proliferation rate was further reduced, and the apoptosis rate was significantly increased after co-transfection of miR-223 silencing vector and AQP-1 silencing vector. AQP-1 protein was highly expressed in SW579 cells, and miR-223 inhibitor can down-regulate the expression of APQ-1 protein. The expression AQP-1 protein was significantly reduced after transfected with AQP-1 silencing vector. Inhibition of miR-223 expression could suppress proliferation and promote apoptosis of SW579, and its mechanism is related to down-regulation of APQ-1 protein expression.

Next-generation Metabolomics in the Development of New Antidepressants: Using Albiflorin as an Example.

Depression is a highly prevalent disorder that affects more than 300 million adults worldwide in 2015. Depression also frequently coexists with many other conditions such as osteoporosis and one-third of the Intensive Care Unit (ICU) survivors had depressive symptoms. Antidepressants have become the most commonly prescribed drugs in the United States. In addition to the regular process, drug discovery and development (R&D) for depression presents extra challenges because of the heterogeneity of the symptoms and various co-occurring disorders. Botanical medicine with multi-functional nature has been proposed to be more effective, providing rapid control of core and comorbid conditions of depression. With the technical advances in analytical instruments, metabolomics is entering into a "new generation". Next-generation metabolomics (NGM) has the capability to comprehensively characterize drug-induced metabolic changes in the biological systems. NGM has demonstrated great potential in all the stages of pharmaceutical R&D in the last 10 years. Albiflorin isolated from Peony roots is a promising drug candidate with multi-target for depression and is currently under development by Beijing Wonner Biotech. In this work, we summarized the common analytical platforms for NGM and its main applications in drug R&D. We used albiflorin as an example to illustrate how NGM improves our understanding of drug candidate actions and facilitates drug safety evaluation. Future directions on how to expand the use of NGM for new antidepressant development in pharmaceutical industry were also discussed.

In vivo HMRS and lipidomic profiling reveals comprehensive changes of hippocampal metabolism during aging in mice.

Aging is characterized by various cellular changes in the brain. Hippocampus is important for systemic aging and lifespan control. There is still a lack of comprehensive overview of metabolic changes in hippocampus during aging. In this study, we first created an accelerated brain aging mice model through the chronic administration of d-galactose. We then performed a multiplatform metabolomic profiling of mice hippocampus using the combination of in vivo 9.4 T HMRS and in vitro LC-MS/MS based lipidomics. We found N-acetylaspartic acid (NAA), gama-aminobutyric acid (GABA), glutamate/glutamine, taurine, choline, sphingolipids (SMs), phosphatidylethanolamines (PEs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs) and phosphatidylserines (PSs), all of them decreasing with the aging process in mice hippocampus. The changes of sphingolipids and phospholipids were not limited to one single class or molecular species. In contrast, we found the significant accumulation of lactate, myoinositol and phosphatidylcholines (PCs) along with aging in hippocampus. SM (d18:1/20:2), PE (36:2), PG (34:1), PI (36:4), PS (18:0/20:4) and PC (36:0) have the most significant changes along with aging. Network analysis revealed the striking loss of biochemical connectivity and interactions between hippocampal metabolites with aging. The correlation pattern between metabolites in hippocampus could function as biomarkers for aging or diagnosis of aging-related diseases.