Abstract. Flavin adenine dinucleotide (FAD) is an essential coenzyme for glutathione reductase (GR) which catalyzes the reduction of oxidized glutathione to regenerate the reduced form involved in protection against oxidative stress. Riboflavin kinase (RFK) also known as flavokinase is involved in the first step of bioactivation of riboflavin (RF) to form flavin mononucleotide (FMN) which can be subsequently converted to FAD in an ATP-dependent reaction catalyzed by FAD synthetase (FADS). We investigated the involvement of RFK in cisplatin resistance using human prostate cancer PC3 cells. RFK overexpression renders cells resistant not only to cisplatin but also to hydrogen peroxide (H 2 O 2 ) and diamide. Furthermore, knockdown of RFK expression induced apoptosis. We demonstrated that overexpression of RFK increased the levels of FAD, FMN and total glutathione and the expression of GR and glutathione S-transferase-π (GSTπ). RFK expression is up-regulated in cisplatin-resistant P/CDP6 cells in addition to FAD, total glutathione level, GR and GSTπ. Knockdown of RFK expression also sensitized both PC3 and P/CDP6 cells to cisplatin. Moreover, cellular levels of RFK expression correlate well with Gleason score, known as a good indicator of patient prognosis. The present study suggests that RFK expression is involved not only in cellular protection from oxidative stress but also in malignant progression of prostate cancer.

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Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related protein (DC-SIGNR) is a type II transmembrane protein that has been reported to bind to various pathogens and participate in immunoregulation and tumorigenesis. However, further research is required to investigate whether the level of DC-SIGNR and cervical cancer are associated. The present study aimed to explore the clinical diagnostic significance of DC-SIGNR in cervical cancer. Immunohistochemical staining of DC-SIGNR was performed in samples from 25 patients with early stage cervical cancer, 14 patients with cervical intraepithelial neoplasia (CIN) and cervical polyp samples from 15 individuals. DC-SIGNR expression in cervical cancer tissue was significantly higher compared with that in CIN and cervical polyp tissue (P=0.0184 and P=0.0236, respectively). However, there was no significant difference in DC-SIGNR expression between CIN and cervical polyp tissue (P=0.8103). Additionally, the serum DC-SIGNR levels in 84 cervical cancer patients and 69 healthy female individuals were measured using an ELISA. Serum (s)DC-SIGNR levels were significantly higher in cervical cancer patients compared with healthy female individuals (P<0.0001). A sDC-SIGNR level of 93.7 ng/ml was revealed by receiver operating characteristic curve analysis to predict the presence of cervical cancer with 69.57% sensitivity and 66.67% specificity (area under the curve, 0.6989; P<0.0001). Levels of sDC-SIGNR in cervical cancer patients were also correlated with serum levels of squamous cell carcinoma antigen (r=0.2583; P=0.0348). The results of the present study demonstrate that DC-SIGNR is overexpressed in cervical cancer tissue, and suggest that DC-SIGNR could serve as a biomarker for the early diagnosis of cervical cancer. Nevertheless, further studies are required to demonstrate what role DC-SIGNR serves in cervical cancer.

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Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD.