Multifunctional nanomedicines-enabled chemodynamic-synergized multimodal tumor therapy via Fenton and Fenton-like reactions.

Chemodynamic therapy (CDT) is well-known for using the tumor microenvironment to activate the Fenton reaction or Fenton-like reaction to generate strong oxidative hydroxyl radicals for tumor-specific treatment. It is highly selective and safe, without depth limitation of tissue penetration, and shows its potential as a new green therapeutic method with great clinical application. However, the catalytic efficiency of reagents involved in the Fenton reaction is severely affected by the inherent microenvironmental limitations of tumors and the strict Fenton reaction-dependent conditions. With the increasing application of nanotechnology in the medical field, combined therapies based on different types of functional nanomaterials have opened up new avenues for the development of next-generation CDT-enhanced system. This review will comprehensively exemplify representative results of combined therapies of CDT with other antitumor therapies such as chemotherapy, phototherapy, sonodynamic therapy, radiation therapy, magnetic hyperthermia therapy, immunotherapy, starvation therapy, gas therapy, gene therapy, oncosis therapy, or a combination thereof for improving antitumor efficiency from hundreds of the latest literature, introduce strategies such as the ingenious design of nanomedicines and tumor microenvironment regulations to enhance the combination therapy, and further summarize the challenges and future perspective of CDT-based multimodal anticancer therapy.

Progressive increase of high-frequency EEG oscillations during meditation is associated with its trait effects on heart rate and proteomics: a study on the Tibetan Buddhist.

Meditation has been a spiritual and healing practice in the East for thousands of years. However, the neurophysiologic mechanisms underlying its traditional form remain unclear. In this study, we recruited a large sample of monks (n = 73) who practice Tibetan Buddhist meditation and compared with meditation-naive local controls (n = 30). Their electroencephalography (EEG) and electrocardiogram signals were simultaneously recorded and blood samples were collected to investigate the integrative effects of Tibetan Buddhist on brain, heart, and proteomics. We found that the EEG activities in monks shifted to a higher frequency from resting to meditation. Meditation starts with decrease of the (pre)frontal delta activity and increase of the (pre)frontal high beta and gamma activity; while at the deep meditative state, the posterior high-frequency activity was also increased, and could be specified as a biomarker for the deep meditation. The state increase of posterior high-frequency EEG activity was significantly correlated with the trait effects on heart rate and nueropilin-1 in monks, with the source of brain-heart correlation mainly locating in the attention and emotion networks. Our study revealed that the effects of Tibetan Buddhist meditation on brain, heart, and proteomics were highly correlated, demonstrating meditation as an integrative body-mind training.

Self-Assembly Nanoparticles for Overcoming Multidrug Resistance and Imaging-Guided Chemo-Photothermal Synergistic Cancer Therapy.

BACKGROUND AND PURPOSE: The development of multiple drug resistance (MDR) to chemotherapy and single modal therapy remains unsatisfied for the eradication of tumor, which are major obstacles in cancer therapy. This novel system with excellent characteristics for inhibition of P-glycoprotein (P-gp), and for near-infrared fluorescence (NIRF) imaging-guided chemo-photothermal therapy (PTT), has been identified as a promising way to MDR and achieve synergistic cancer therapy. METHODS: In this study, we successfully synthesized a multifunctional theranostic system, which was developed through FDA-approved self-assembling drugs, which contain anticancer drug doxorubicin (Dox), imaging and high photothermal conversion drug indocyanine green (ICG) and P-gp regulator TPGS (the system named T/Dox-ICG). We studied the characterization of T/Dox-ICG NPs, including the TEM, SEM, DLS, UV-vis-NIR, zeta potential, CLSM, in vitro FL imaging, in vitro photothermal effect, in vitro Dox and ICG release. We used CLSM to verify the location of intracellular distribution of Dox in SCG 7901/VCR cells, Western blot was performed to demonstrate the TPGS-mediated inhibition of P-gp. And, the cytotoxicity of materials against SCG 7901/VCR cells was studied by the MTT assay. RESULTS: The TEM showed the T/Dox-ICG NPs had good monodispersity with diameters of 19.03 nm, Dox and ICG could be released constantly from T/Dox-ICG NPs in vitro. In vitro cell experiments demonstrated higher Dox accumulation and retention in the nucleus. Western blot showed TPGS could obviously inhibit the expression of P-gp. In vitro cytotoxicity assay showed more significant cytotoxicity on MDR cells (SCG 7901/VCR) with only 8.75% of cells surviving. CONCLUSION: MDR cancer therapy indicates that it may be important to develop a safer system that can simultaneously inhibit the drug transporters and monitor the delivery of chemotherapeutic agents, and combination therapy have raised widespread concern on tumor treatment.

The association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders in children: a meta-analysis.

Previous reviews have been conducted to evaluate the association between maternal use of folic acid supplements during pregnancy and risk of autism spectrum disorders (ASD) in children, with no definitive conclusion. We therefore conducted a more comprehensive meta-analysis to reassess the relationship between folic acid and the risk of ASD. The electronic databases PubMed, Web of Knowledge, and Wanfang Data were carefully searched to find eligible studies as recent as March 2017. A random effects model was used to combine the relative risk (RR) with 95% confidence intervals (CI). Sensitivity analysis and publication bias were conducted. A total of 12 articles with 16 studies comprising 4514 ASD cases were included in this report. It was found that supplementation with folic acid during pregnancy could reduce the risk of ASD [RR = 0.771, 95% CI = 0.641-0.928, I2  = 59.7%, Pheterogeneity = 0.001] as compared to those women without folic acid supplementation. The associations were significant among Asian, European, and American populations. In summary, this comprehensive meta-analysis suggested that maternal use of folic acid supplements during pregnancy could significantly reduce the risk of ASD in children regardless of ethnicity, as compared to those women who did not supplement with folic acid.

Alterations in regional homogeneity of resting-state cerebral activity in patients with chronic prostatitis/chronic pelvic pain syndrome.

The purpose of this study was to explore the neural mechanism in Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) using resting-state functional magnetic resonance imaging. The functional magnetic resonance imaging was performed on 31 male CP/CPPS-patients and 31 age and education matched male healthy controls on a 3-T magnetic resonance imaging unit. A two-sample t-test was adopted to reveal the regional homogeneity between the patients and healthy controls. The mean regional homogeneity values in the alerted brain regions of patients were correlated with the clinical measurements by using Pearson's correlation analyses. The CP/CPPS-patients had significantly decreased regional homogeneity in the bilateral anterior cingulate cortices, insular cortices and right medial prefrontal cortex, while significantly increased regional homogeneity in the brainstem and right thalamus compared with the healthy controls. In the CP/CPPS-patients, the mean regional homogeneity value in the left anterior cingulate cortex, bilateral insular cortices and brainstem were respectively correlated with the National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscale. These brain regions are important in the pain modulation process. Therefore, an impaired pain modulatory system, either by decreased descending pain inhibition or enhanced pain facilitation, may explain the pain symptoms in CP/CPPS.

Self-regulation of brain activity in patients with postherpetic neuralgia: a double-blind randomized study using real-time FMRI neurofeedback.

BACKGROUND: A pilot study has shown that real-time fMRI (rtfMRI) neurofeedback could be an alternative approach for chronic pain treatment. Considering the relative small sample of patients recruited and not strictly controlled condition, it is desirable to perform a replication as well as a double-blinded randomized study with a different control condition in chronic pain patients. Here we conducted a rtfMRI neurofeedback study in a subgroup of pain patients - patients with postherpetic neuralgia (PHN) and used a different sham neurofeedback control. We explored the feasibility of self-regulation of the rostral anterior cingulate cortex (rACC) activation in patients with PHN through rtfMRI neurofeedback and regulation of pain perception. METHODS: Sixteen patients (46-71 years) with PHN were randomly allocated to a experimental group (n = 8) or a control group (n = 8). 2 patients in the control group were excluded for large head motion. The experimental group was given true feedback information from their rACC whereas the control group was given sham feedback information from their posterior cingulate cortex (PCC). All subjects were instructed to perform an imagery task to increase and decrease activation within the target region using rtfMRI neurofeedback. RESULTS: Online analysis showed 6/8 patients in the experimental group were able to increase and decrease the blood oxygen level dependent (BOLD) fMRI signal magnitude during intermittent feedback training. However, this modulation effect was not observed in the control group. Offline analysis showed that the percentage of BOLD signal change of the target region between the last and first training in the experimental group was significantly different from the control group's and was also significantly different than 0. The changes of pain perception reflected by numerical rating scale (NRS) in the experimental group were significantly different from the control group. However, there existed no significant correlations between BOLD signal change and NRS change. CONCLUSION: Patients with PHN could learn to voluntarily control over activation in rACC through rtfMRI neurofeedback and alter their pain perception level. The present study may provide new evidence that rtfMRI neurofeedback training may be a supplemental approach for chronic clinical pain management.