Using Neurofeedback from Steady-State Visual Evoked Potentials to Target Affect-Biased Attention in Augmented Reality.

Biases in attention to emotional stimuli (i.e., affect-biased attention) contribute to the development and mainte-nance of depression and anxiety and may be a promising target for intervention. Past attempts to therapeutically modify affect-biased attention have been unsatisfactory due to issues with reliability and precision. Electroencephalogram (EEG)-derived steady-state visual evoked potentials (SSVEPS) provide a temporally-sensitive biological index of attention to competing visual stimuli at the level of neuronal populations in the visual cortex. SSVEPS can potentially be used to quantify whether affective distractors vs. task-relevant stimuli have "won" the competition for attention at a trial-by-trial level during neuro-feedback sessions. This study piloted a protocol for a SSVEP-based neurofeedback training to modify affect-biased attention using a portable augmented-reality (AR) EEG interface. During neurofeedback sessions with five healthy participants, signifi-cantly greater attention was given to the task-relevant stimulus (a Gabor patch) than to affective distractors (negative emotional expressions) across SSVEP indices (p<0.000l). SSVEP indices exhibited excellent internal consistency as evidenced by a maximum Guttman split-half coefficient of 0.97 when comparing even to odd trials. Further testing is required, but findings suggest several SSVEP neurofeedback calculation methods most deserving of additional investigation and support ongoing efforts to develop and implement a SSVEP-guided AR-based neurofeedback training to modify affect-biased attention in adolescent girls at high risk for depression.

Graph-based Recurrence Quantification Analysis of EEG Spectral Dynamics for Motor Imagery-based BCIs.

Despite continuous research, communication approaches based on brain-computer interfaces (BCIs) are not yet an efficient and reliable means that severely disabled patients can rely on. To date, most motor imagery (MI)-based BCI systems use conventional spectral analysis methods to extract discriminative features and classify the associated electroencephalogram (EEG)-based sensorimotor rhythms (SMR) dynamics that results in relatively low performance. In this study, we investigated the feasibility of using recurrence quantification analysis (RQA) and complex network theory graph-based feature extraction methods as a novel way to improve MI-BCIs performance. Rooted in chaos theory, these features explore the nonlinear dynamics underlying the MI neural responses as a new informative dimension in classifying MI. METHOD: EEG time series recorded from six healthy participants performing MI-Rest tasks were projected into multidimensional phase space trajectories in order to construct the corresponding recurrence plots (RPs). Eight nonlinear graph-based RQA features were extracted from the RPs then compared to the classical spectral features through a 5-fold nested cross-validation procedure for parameter optimization using a linear support vector machine (SVM) classifier. RESULTS: Nonlinear graph-based RQA features were able to improve the average performance of MI-BCI by 5.8% as compared to the classical features. SIGNIFICANCE: These findings suggest that RQA and complex network analysis could represent new informative dimensions for nonlinear characteristics of EEG signals in order to enhance the MI-BCI performance.

Demethyleneberberine induces cell cycle arrest and cellular senescence of NSCLC cells via c-Myc/HIF-1α pathway.

BACKGROUND: Demethyleneberberine (DMB) is a natural active component of medicinal plant Cortex phellodendri chinensis with favorable bioactivity. However, the role of DMB in suppressing non-small cell lung cancer (NSCLC) remains unknown. PURPOSE: In this study, we aimed to examine the effect and underlying mechanism of DMB in suppressing NSCLC. METHODS: CCK8 assay and colony formation assay were utilized to assess the efficiency of DMB on the viability and colony formation capacity of NSCLC cells. Flow cytometry and ß-Galactosidase Staining Kit were utilized to determine the efficiency of DMB on the cell cycle and cellular senescence of NSCLC cells. RT-qPCR and Western blot were used to detect the effect of DMB on cell cycle and cellular senescence related gene and protein expression of NSCLC cells. In vivo tumor model was established to evaluate the anti NSCLC effect of DMB. In addition, RNA-seq analysis was performed to detect the differential gene expression after DMB treatments. RESULTS: In this study, we revealed that DMB exhibits efficient inhibitory effect on NSCLC cell proliferation and tumor xenografts growth in vivo. We also demonstrated that DMB could inhibit cell migration by suppressing epithelial-mesenchymal transition (EMT) and trigger cell cycle arrest by down-regulating the expression of cell cycle related genes in NSCLC cells. In addition, DMB treatment efficiently induces cellular senescence of NSCLC cells. From the RNA-seq analysis, we found that DMB accelerates senescence through suppressing HIF-1α expression, which was further elucidated by overexpressing HIF-1α in NSCLC to reduce the inhibitory effect of DMB. Furthermore, we also revealed that DMB decreases the expression of c-Myc, an up-stream protein of HIF-1α. CONCLUSIONS: Taken together, we first report that DMB inhibits NSCLC progress through inducing cell cycle arrest and triggering cellular senescence by downregulating c-Myc/HIF-1α pathway.

Insight into the roles of melatonin in bone tissue and bone­related diseases (Review).

Bone­related diseases comprise a large group of common diseases, including fractures, osteoporosis and osteoarthritis (OA), which affect a large number of individuals, particularly the elderly. The progressive destruction and loss of alveolar bone caused by periodontitis is a specific type of bone loss, which has a high incidence and markedly reduces the quality of life of patients. With the existing methods of prevention and treatment, the incidence and mortality of bone­related diseases are still gradually increasing, creating a significant financial burden to societies worldwide. To prevent the occurrence of bone­related diseases, delay their progression or reverse the injuries they cause, new alternative or complementary treatments need to be developed. Melatonin exerts numerous physiological effects, including inducing anti­inflammatory and antioxidative functions, resetting circadian rhythms and promoting wound healing and tissue regeneration. Melatonin also participates in the health management of bone and cartilage. In the present review, the potential roles of melatonin in the pathogenesis and progression of bone injury, osteoporosis, OA and periodontitis are summarized. Furthermore, the high efficiency and diversity of the physiological regulatory effects of melatonin are highlighted and the potential benefits of the use of melatonin for the clinical prevention and treatment of bone­related diseases are discussed.

CuS-NiS2 nanomaterials for MRI guided phototherapy of gastric carcinoma via triggering mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

Gastric carcinoma is one of the most lethal malignant tumors. As part of our long-term efforts on seeking effective diagnosis and therapeutic strategies of gastric cancer, we present herein novel ternary copper-based chalcogenide nanoplatform CuS-NiS2 nanomaterials with outstanding photothermal (PT)/photodynamic (PD) property that could effectively suppress human gastric cancer in vitro and in vivo without obvious side effects. We revealed that CuS-NiS2 induced reactive oxygen species (ROS) generation, leading to apoptosis through Bcl-2/Bax pathway of human gastric cancer cells under 808 nm near-infrared (NIR) irradiation. In addition, we also confirmed that the combination of CuS-NiS2 and 808 nm NIR laser treatment triggered necroptosis by regulating the novel pathway MLKL/CAPG of human gastric cancer cells. Moreover, the CuS-NiS2 exhibited excellent contrast enhancement according to magnetic resonance imaging (MRI). Taken together, we reported new ternary copper-based chalcogenide nanomaterials CuS-NiS2, which could be successfully applied for MRI-guided PT/PD therapy of gastric carcinoma through mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

FuFangChangTai Decoction Activates Macrophages via Inducing Autophagy.

The traditional Chinese medicine decoction FuFangChangTai (FFCT) has been used in the therapy of colon cancer clinically, yielding alleviated toxicity and enhanced immunity. In our previous study, FFCT exerted its antitumor activity not only by inducing apoptosis but also by activating autophagy to eliminate tumor cells. However, its mechanism is not well understood. The purpose of this study was to investigate the relationship between macrophages activation and FFCT-induced autophagy. Results showed that FFCT could induce autophagy in colon cancer, as demonstrated by increased level of intracellular autophagy marker LC3 II in CT26.WT cells by fluorescence microscope and western blot assay. FFCT also facilitated numbers of vesicular bodies with bilayer membrane in CT26.WT cells, which were indicative of autophagosomes formation. Autophagosomes secreted by FFCT-treated CT26.WT cells can activate M1 type macrophages, accompanied with increased expression of costimulatory molecules CD86 and CD40 on the surface of RAW264.7 cells, and more inflammatory cytokines secretion, such as TNF-α, IL-6, MCP-1, and IL-1ß. mRNA expressions of M2 macrophages markers, such as IL-10, CD206, Arg-1, and FIZZ-1, were downregulated. And this process helps regulate the polarization of macrophages and promote the immune response. These findings support a mechanism of FFCT-induced autophagy and provide novel evidence demonstrating that macrophages are involved in FFCT-induced autophagy progression.

Extracellular signal-regulated kinase, substance P and neurokinin-1 are involved in the analgesic mechanism of herb-partitioned moxibustion.

Herb-partitioned moxibustion can effectively mitigate visceral pain, a major symptom in inflammatory bowel disease, but the analgesic mechanism is still unclear. Moreover, extracellular signal-regulated kinase, substance P, and neurokinin-1 are involved in formation of central hyperalgesia. Thus, we postulated that the analgesic effect of herb-partitioned moxibustion may be associated with these factors. Accordingly, in this study, we established an inflammatory bowel disease visceral pain model in rat by enema with a mixed solution of 5% trinitrobenzenesulfonic acid and 50% ethanol. Bilateral Tianshu (ST25) and Qihai (CV6) points were selected for herb-partitioned moxibustion. Our results showed that herb-partitioned moxibustion improved visceral pain and down-regulated extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA expression in dorsal root ganglia. These results indicate that down-regulation of extracellular signal-regulated kinase, substance P, and neurokinin-1 protein and mRNA may be a central mechanism for the analgesic effect of herb-partitioned moxibustion.

The rationality of the hypolipidemic effect of alismatis rhizoma decoction, a classical chinese medicine formula in high-fat diet-induced hyperlipidemic mice.

Alismatis Rhizoma Decoction (ARD) is a classical Traditional Chinese Medicine (TCM) formula for treatment of vertigo with its long history of successful clinical effect. Since vertigo is a symptom of hyperlipidemia, this study aimed at evaluating the hypolipidemic effect of ARD in hyperlipidemic mice induced by high fat diet (HFD) and investigated the rationality of formula combination of Alismatis Rhizoma (AR) and Atractylodis Macrocephalae Rhizoma (AMR). Compared with control group, hyperlipidemic mice in AR and ARD groups displayed a reduction of the following parameters: body weight, liver and serum total cholesterol, triglyceride concentration, liver and spleen coefficients, activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT); whereas the serum HDL-cholesterol levels were significantly elevated in both AR and ARD groups. AR and ARD treatments significantly down regulated the expressions of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoA reductase) and sterol regulatory element binding factor-2 (SREBF-2). These findings clearly provided evidences that the suppression on biosynthesis of cholesterol in liver may in part contribute to the hypolipidemic effects of ARD and AR. Since no significantly hypolipidemic effect of AMR was observed, the more prominent effect of ARD than that of AR indicated synergistic effects of AR and AMR, and confirmed the rationality of ARD formula.

[Artesunate induces prostate cancer cell line PC-3 differentiation and cell cycle arrest].

OBJECTIVE: To explore the effect of artesunate (ART) on cell differentiation and cell cycle distribution of the prostate cancer cell line PC-3 in vitro. METHODS: PC-3 cells were cultivated with ART from logarithmic growth phase. After 48-hour treatment, the cell cycles were detected by flow cytometry (FCM), and enzyme linked immunosorbent assay was used to detect the level of prostate specific antigen (PSA) in cell culture supernatant. The change of cellular morphology was observed under a transmission electron microscope (TEM). RESULTS: In comparison with the blank control group, the rate of G(0)/G(1) plus S stages of PC-3 cells was significantly decreased in the high-dose ART group. The PC-3 cell was arrested in G(2)/M by ART. The rates of G(2)/M of the high-dose ART group and the medium-dose ART group were obviously higher than those of the blank control group and the cisplatin group (P<0.05). The levels of PSA in the three ART groups were significantly lower than that of the normal control group (P<0.05, P<0.01). In the ART groups, TEM showed that some vacuoles appeared in endochylema, cell polarity was enhanced, cell nucleus leaned to one side of the cell, and microvilli increased on the other side of the cell. CONCLUSION: ART can induce PC-3 cell cycle arrest and differentiation in vitro.