PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer.

Cervical cancer, one of the most common malignancies, has a poor survival rate. The identification of more biomarkers for cervical cancer diagnosis and therapy is urgently needed. Plasminogen activator urokinase (PLAU) exerts multiple biological effects in various physiological and pathological processes; however the role of PLAU in cervical cancer progression is not fully understood. In the present study, the involvement and transcriptional regulation of PLAU in cervical cancer were explored. The expression of PLAU in cervical cancer was first analyzed, and PLAU was found to be overexpressed. In vitro experiments demonstrated that the migration and invasion of HeLa and HT3 cells were significantly suppressed by PLAU knockdown. Additionally, the core promoter of PLAU was confirmed, and the transcription factor YinYang 1 (YY1) was found to regulate PLAU mRNA expression. Overall, the present study elucidated the direct association between PLAU and cervical cancer, suggesting the YY1/PLAU axis as a potential novel therapeutic target for cervical cancer.

Effects of titanium dioxide nanoparticles on nutrient absorption and metabolism in rats: distinguishing the susceptibility of amino acids, metal elements, and glucose.

Food grade titanium dioxide (TiO2) containing nanofractions, is commonly applied to whiten and brighten food products, which put consumers under health risks of ingesting TiO2 nanoparticles (NPs). Although the oral toxicity of TiO2-NPs has been evaluated in several studies, gaps in knowledge exist regarding interactions between NPs and food components. Therefore, this study aimed to estimate the influence of TiO2-NPs on nutrient absorption and metabolism through an in situ intestinal loop experiment which conducted on adult Sprague Dawley (SD) rats after 30-d gastrointestinal exposure to TiO2-NPs of two different sizes (N-TiO2 and M-TiO2). Results showed that exposure to TiO2-NPs caused flat apical membranes with sparse and short microvilli and inflammatory infiltration in small intestine. Both particles were absorbed into small intestinal cells, but N-TiO2 with smaller size could more easily be transported through gut and raise the blood titanium (Ti) levels. Changes in serum levels of amino acid were also different after exposure to these two particles. After injecting mixed solution of nutrients into in situ intestinal loop, the N-TiO2 exposure groups displayed significant absorption inhibition of the added histidine (His) and metabolism disorder of some non-added amino acid. However, no influence was observed on metal elements or glucose levels. This study identified TiO2-NPs with small sizes could affect nutrient absorption and metabolism by inducing intestinal epithelium injury, and amino acids were more susceptible than metal elements and glucose. These findings suggested that foods supplemented with TiO2-NPs should be carefully consumed by people with high protein requirements, such as children, the elderly, and patients with high metabolic disease or intestinal inflammation.

M2 macrophages mediate sorafenib resistance by secreting HGF in a feed-forward manner in hepatocellular carcinoma.

BACKGROUND: Sorafenib is the only approved first line systemic therapy for advanced hepatocellular carcinoma (HCC) in the last decade. Tumour resistance to sorafenib has been of major obstacles to improve HCC patient survival. METHODS: We polarised THP-1 cells to M1 and M2 macrophages, performed various in vitro assays and developed sorafenib-resistant xenograft models to investigate the role of tumour-associated macrophages (TAM)-secreted molecules in HCC resistance to the targeted therapy. RESULTS: We demonstrated M2, but not M1, macrophages not only promote proliferation, colony formation and migration of hepatoma cells but also significantly confer tumour resistance to sorafenib via sustaining tumour growth and metastasis by secreting hepatocyte growth factor (HGF). HGF activates HGF/c-Met, ERK1/2/MAPK and PI3K/AKT pathways in tumour cells. Tumour-associated M2 macrophages were accumulated in sorafenib-resistance tumours more than in sorafenib-sensitive tumours in vivo and produced abundant HGF. HGF chemoattracts more macrophages migrated from surrounding area, regulates the distribution of M2 macrophages and increases hepatoma resistance to sorafenib in a feed-forward manner. CONCLUSIONS: Our results provide new insights into the mechanisms of sorafenib resistance in HCC and rationale for developing new trials by combining sorafenib with a potent HGF inhibitor such as cabozantinib to improve the first line systemic therapeutic efficacy.

Hypothalamus-anchored resting brain network changes before and after sertraline treatment in major depression.

Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline) on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients (n = 12) both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.