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The present study aimed to screen potential genes associated with metastatic prostate cancer (PCa), in order to improve the understanding of the mechanisms underlying PCa metastasis. The GSE3325 microarray dataset, which was downloaded from the Gene Expression Omnibus database, consists of seven clinically localized PCa samples, six hormone-refractory metastatic PCa samples and six benign prostate tissue samples. The Linear Models for Microarray Data package was used to identify differentially-expressed genes (DEGs) and a hierarchical cluster analysis for DEGs was performed with the pheatmap package. Furthermore, potential functions for the DEGs were predicted by a functional enrichment analysis. Subsequently, microRNAs (miRNAs) potentially involved in the regulation of PCa metastasis were identified by WebGestalt software, and the miRNA-DEG regulatory network was visualized using Cytoscape. In addition, a pathway enrichment analysis for DEGs in the regulatory network was performed. A total of 306 and 2,073 genes were differentially expressed in the clinically localized PCa and the metastatic PCa groups, respectively, as compared with the benign prostate group, of which 174 were differentially expressed in both groups. A number of the DEGs, including CAMK2D and SH3BP4, were significantly enriched in the cell cycle, and others, such as MAF, were associated with the regulation of cell proliferation. Furthermore, some DEGs (CAMK2D and PCDH17) were observed to be regulated by miR-30, whereas others (ADCY2, MAF, SH3BP4 and PCDH17) were modulated by miR-182. Additionally, ADCY2 and CAMK2D were distinctly enriched in the calcium signaling pathway. The present study identified novel DEGs, including ADCY2, CAMK2D, MAF, SH3BP4 and PCDH17, that may be involved in the metastasis of PCa. [ABSTRACT FROM AUTHOR]

Dimer nanostructure as a pair of closely-spaced metal nanoparticles supports the localized surface plasmon (LSP) forming in designed area, showing signal enhancement and chirality, and it can offer a fundamental approach to studying the photonic interaction between nanoparticles. Thus an efficient way to realize dimer nanostructures with controllable gap size is important for the study of LSP resonance. In this paper, angle evaporation of Au is utilized to realize the varied dimer gap within tens of nm leading to the efficient adjusting of LSP resonance. Experimental results coupled with theoretical FDTD simulations revealed strong polarization-dependent transmission bands at the adjustable LSP resonance. The theoretical study showed an enhancement of over 2000 times of the localized electrical field intensity confined within dimer gap. Our method is expected to realize large-area LSP nanostructures for the application in metamaterial and chemical sensing. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to quantify the cumulative randomized evidence for the efficacy and safety of lapatinib combined with neoadjuvant therapy in human epidermal growth factor receptor (HER) 2-positive breast cancer. Three electronic databases, MEDLINE, Embase and Cochrane Central Register of Controlled Trials, and the abstracts of major international conferences between inception and 15 December 2013 were searched. Two evaluators independently extracted data. The end-points assessed consisted of the pathological complete response (pCR) rate, breast-conserving surgery (BCS) rate and the occurrence of adverse events. Four randomized controlled trials were assessed in the present study, involving a total of 779 participants. Compared with the patients who did not receive lapatinib, the pCR rate was higher in the hormone receptor (HR)-positive [risk ratio (RR), 1.39; 95% confidence interval (CI), 1.12-1.72; P=0.002) and HR-negative (RR, 1.38; 95% CI, 1.14-1.68; P=0.0009) patients that received lapatinib. No significant difference between the BCS rate of the two treatment arms was observed in two trials (n=382; RR, 1.14; 95% CI, 0.89-1.47; P=0.31). The primary adverse events, including diarrhea, dermatological toxicity, hepatic toxicity and neutropenia, were statistically more frequent in patients that received lapatinib (RR, 2.46; 95% CI, 1.97-3.07; P<0.00001). The present analysis revealed that the addition of lapatinib to neoadjuvant chemotherapy for HER2-positive breast cancer improves the probability of achieving a higher pCR rate, but the use of lapatinib is associated with a higher risk of adverse events. [ABSTRACT FROM AUTHOR]

Introduction: Transoral vestibular endoscopic thyroidectomy (TOET) is sometimes used in young and middle-aged patients with papillary thyroid microcarcinoma (PTMC), but it is still difficult to identify lymph nodes (LNs) and parathyroid glands (PGs). Carbon nanoparticle (CN) is a novel lymph node tracer and has been widely used in open thyroid surgery. Aim: To evaluate the efficacy of CN in identifying LNs and preserving PGs in TOET with central neck dissection (CND). Material and methods: A total of 72 PTMC patients undergoing TOET with CND were retrospectively enrolled from January 2017 to January 2019. Patients were divided into a CN group (n = 38) and a control group (n = 34). The parameters including pathological characteristics, surgery related indicators, serum Ca2+ and parathyroid hormone (PTH) levels were compared. Results: No significant differences were found in patient characteristics, operative complications and superior PGs preserved in situ (all p > 0.05). Total LNs and number of LNs less than 5 mm were significantly higher in the CN group than in the control group (p = 0.021, p < 0.01). The number of superior PGs preserved in situ discovered in the CN group was greater than the control group (p = 0.038). Serum PTH and Ca2+ levels dropped markedly in each group after surgery and gradually recovered in time. The CN group recovered faster than the control group. Conclusions: CN may be a good choice for TOET for PTMC because of better protection and faster recovery of parathyroid function, and more LNs removed. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs)-derived dopaminergic neurons might be reset back to the fetal state due to reprogramming. Thus, it is a compelling challenge to reliably and efficiently induce disease phenotypes of iPSCs-derived dopaminergic neurons to model late-onset Parkinson's disease (PD). Here, we applied a small molecule, hydroxyurea (HU), to promote the manifestation of disease relevant phenotypes in iPSCs-based modeling of PD. We established two iPS cell lines derived from two sporadic PD patients. Both patients-iPSCs-derived dopaminergic neurons did not display PD relevant phenotypes after 6 weeks culture. HU treatment remarkably induced ER stress on patients-iPSCs-derived dopaminergic neurons. Moreover, HU treatment significantly reduced neurite outgrowth, decreased the expression of p-AKT and its downstream targets (p-4EBP1 and p-ULK1), and increased the expression level of cleaved-Caspase 3 in patients-iPSCsderived dopaminergic neurons. The findings of the present study suggest that HU administration could be a convenient and reliable approach to induce disease relevant phenotypes in PD-iPSCs-based models, facilitating to study disease mechanisms and test drug effects. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of upper and lower motor neurons. The disease progression is associated with the astrocytic environment. Aquaporin-4 (AQP4) water channels are the most abundant AQPs expressed in astrocytes, exerting important influences on central nervous system homeostasis. The present study aimed to characterize the alterations in AQP4 expression and localization in superoxide dismutase 1 (SOD1) G93A transgenic mice. SOD1G93A mice were sacrificed during the presymptomatic, disease onset and end stages and immunostaining was performed on spinal cord sections to investigate neuronal loss, glial activation and AQP4 expression in the spinal cord. It was observed that global AQP4 expression increased in the spinal cord of SOD1G93A mice as the disease progressed. However, AQP4 polarization decreased as the disease progressed, and AQP4 polarized localization at the endfeet of astrocytes was decreased in the spinal ventral horn of SOD1G93A mice at the disease onset and end stages. Meanwhile, motor neuron degeneration and decreased glutamate transporter 1 expression in astrocytes in SOD1G93A mice were observed as the disease progressed. The results of the present study demonstrated that AQP4 depolarization is a widespread pathological condition and may contribute to motor neuron degeneration in ALS. [ABSTRACT FROM AUTHOR]

Impairment of amyloid-ß (Aß) clearance leads to Aß accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aß clearance from the brain and resist Aß injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aß. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after Aß injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing Aß accumulation via mediating the glymphatic system function. [ABSTRACT FROM AUTHOR]

Ginsenosides exhibit various neuroprotective effects against oxidative stress. However, which ginsenoside provides optimal effects for the treatment of neurological disorders as a potent antioxidant remains to be elucidated. Therefore, the present study investigated and compared the neuroprotective effects of the Rb1, Rd, Rg1 and Re ginsenosides on neural progenitor cells (NPCs) following tert-Butylhydroperoxide (t-BHP)-induced oxidative injury. Primary rat embryonic cortical NPCs were prepared from E14.5 embryos of Sprague-Dawley rats. The oxidative injury model was established with t-BHP. A lactate dehydrogenase assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining were used to measure the viability of the NPCs pre-treated with ginsenosides under oxidative stress. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the activation of intracellular signaling pathways triggered by the pretreatment of ginsenosides. Among the four ginsenosides, only Rb1 attenuated t-BHP toxicity in the NPCs, and the nuclear factor (erythroizd-derived 2)-like 2/heme oxygenase-1 pathway was found to be key in the intracellular defense against oxidative stress. The present study demonstrated the anti-oxidative effects of ginsenoside Rb1 on NPCs, and suggested that Rb1 may offer potential as a potent antioxidant for the treatment of neurological disorders. [ABSTRACT FROM AUTHOR]

Ki67 has potential prognostic and predictive values for breast cancer patients, and has become an important biomarker in routine clinical practice. The aims of the present study were to investigate the distribution of Ki67 expression and its correlation with other clinicopathological parameters in central China. In total, 1,259 patients with newly-diagnosed invasive breast cancer were included in the present study. The clinical information was obtained from the electronic medical records. The expression levels of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) were detected by immunohistochemical analysis. The associations between Ki67 scores and other prognostic factors were evaluated as continuous and categorical variables. The mean value of the Ki67 scores of all patients was 31%. In total, ~36% (456/1,259) of the patients demonstrated a low expression of Ki67. A statistically significant correlation was identified between the mean Ki67 scores and the lymph node status, tumor grade, ER, PR and HER2 status, and clinical stage or molecular subtypes (all P<0.001). When Ki67 was categorized into high (>14%) and low (≤14%) level groups, the Χ² test was used to verify these results. The Ki67 scores demonstrated no statistically significant differences between the HER2-positive (non-luminal) and three negative subtypes, with the exception of patients with a tumor size of >2 cm (P=0.02). In conclusion, the results revealed the presence of significant correlations between Ki67 and other clinicopathological parameters. [ABSTRACT FROM AUTHOR]