No abstract

No abstract

Breast carcinoma is the most common female cancer with considerable metastatic potential. Signal transducers and activators of the transcription 3 (Stat3) signaling pathway is constitutively activated in many cancers including breast cancer and has been validated as a novel potential anticancer target. Here, we reported our finding with nifuroxazide, an antidiarrheal agent identified as a potent inhibitor of Stat3. The potency of nifuroxazide on breast cancer was assessed in vitro and in vivo. In this investigation, we found that nifuroxazide decreased the viability of three breast cancer cell lines and induced apoptosis of cancer cells in a dose-dependent manner. In addition, western blot analysis demonstrated that the occurrence of its apoptosis was associated with activation of cleaved caspases-3 and Bax, downregulation of Bcl-2. Moreover, nifuroxazide markedly blocked cancer cell migration and invasion, and the reduction of phosphorylated-Stat3Tyr705, matrix metalloproteinase (MMP) MMP-2 and MMP-9 expression were also observed. Furthermore, in our animal experiments, intraperitoneal administration of 50 mg/kg/day nifuroxazide suppressed 4T1 tumor growth and blocked formation of pulmonary metastases without detectable toxicity. Meanwhile, histological and immunohistochemical analyses revealed a decrease in Ki-67-positive cells, MMP-9-positive cells and an increase in cleaved caspase-3-positive cells upon nifuroxazide. Notably, nifuroxazide reduced the number of myeloid-derived suppressor cell in the lung. Our data indicated that nifuroxazide may potentially be a therapeutic agent for growth and metastasis of breast cancer.

Background: Subjective cognitive decline (SCD) may be the first clinical sign of Alzheimer's disease (AD). SCD individuals with normal cognition may already have significant medial temporal lobe atrophy. However, few studies have been devoted to exploring the alteration of left-right asymmetry with hippocampus and amygdala in SCD. The aim of this study was to compare SCD individuals with amnestic mild cognitive impairment (MCI) patients and the normal population for volume and asymmetry of hippocampus, amygdala and temporal horn, and to assess their relationship with cognitive function in elderly population living in China.Methods: 111 SCD, 30 MCI, and 67 healthy controls (HC) underwent a standard T1-weighted MRI, from which the volumes of the hippocampus and amygdala were calculated and compared. Then we evaluated the pattern and extent of asymmetry in hippocampus and amygdala of these samples. Furthermore, we also investigated the relationship between the altered brain regions and cognitive function.Results: Among the three groups, SCD showed more depressive symptoms (p < 0.001) and higher percentage of heart disease (16.4% vs. 35.1%, p = 0.007) than controls. In terms of brain data, significant differences were found in the volume and asymmetry of both hippocampus and amygdala among the three groups (P < 0.05). In logistic analysis controlled by age, gender, education level, depression symptoms, anxiety symptom, somatic disease and lifestyle in terms of smoking, both SCD and MCI individuals showed significant decreased right hippocampal and amygdala volume than controls. For asymmetry pattern, a ladder-shaped difference of left-larger-than-right asymmetry was found in amygdala with MCI>SCD>HC, and an opposite asymmetry of left-less-than-right pattern was found with HC>SCD>MCI in hippocampus. Furthermore, correlation was shown between the volume of right hippocampus and right amygdala with MMSE and MoCA in SCD group.Conclusion: Our results supported that SCD individuals are biologically distinguishable from HC, and this may relate to cognitive impairment, although more longitudinal studies are need to investigate this further.Moreover, different levels of asymmetry in hippocampus and amygdala might be a potential dividing factor to differentiate clinical diagnosis.

No abstract

No abstract

A new azobenzene-bridged cryptand was synthesized; it can be well controlled between cis and trans isomers by irradiation with different wavelengths or by being heated. It was found that this cryptand exhibits an ON-OFF binding ability with 2,7-diazapyrenium (DAP) derivatives. It binds DAP derivatives as the cis isomer only, as demonstrated by various methods. The fluorescence property of DAP derivatives endows these host-guest systems with detectable fluorescent output signals, which makes monitoring these photoresponsive systems convenient.

C ompared to metal and resin, ceramic is the preferred material for fabricating dental restorations, owing to its chemical stability, biocompatibility, and toothlike color. 1,2 In the past decades, the advent and development of subtractive computer-aided design/computer-assisted manufacturing (CAD/CAM) technology have enabled all-ceramic restorations to be reliable, with accurate dimensions and reduced manufacturing time. 2,3 Toughened by phase transformation, yttria-stabilized zirconia ceramic is gaining popularity in clinical practice and has become the first choice for posterior dental restorations. However, the subtractive method requires milling tools, and the costs of the final machining process account for 70% to 80% of the total cost. 4 Besides, introduction of invisible microscopic cracks from the milling process could undermine the strength of the restoration, 5 resulting in a concentration of stress that could potentially lead to clinical failure. To overcome these issues, recent research has explored the feasibility of additive manufacturing of zirconia in