BackgroundThe periaqueductal gray (PAG) dysfunction was recognized in migraine, and the altered dysfunction of PAG subregions were not totally detected up to now. The aim of this study is to investigate the altered functional connectivity of PAG subregions in EM patients.MethodsThe brain structural images and resting state functional MR imaging (rs-fMRI) data were obtained from 18 normal controls (NC) and 18 EM patients on 3.0 T MR system. Seven subregions of PAG were classified as bilateral ventrolateral PAG (vlPAG), lateral PAG (lPAG), dorsolateral PAG (dlPAG) and dorsomedial PAG (dmPAG). The functional connectivity maps of each PAG subregion were calculated, and Two sample t-test was applied with age and sex as covariables.ResultsBilateral vlPAG and left dlPAG presented decreased functional connectivity, and the other subregions (bilateral lPAGs, right dlPAG and dmPAG) showed no significant altered functional connectivity in EM compared with NC. The brain regions with decreased functional connectivity mainly located in bilateral prefrontal cortex(PFC), middle temporal gyrus, primary motor area (PMA) and supplementary motor area (SMA) and right ventrolateral PFC (vlPFC) in EM patients in this study. Disease duration was positively related to the functional connectivity of bilateral vlPAG on the bilateral thalamus and putamen, left pallidum and right medial orbitofrontal gyrus in EM patients.ConclusionThe present study suggested that the dysfunction of bilateral vlPAG and left dlPAG presented in EM, and functional evaluation of PAG subregions may be help for the diagnosis and understanding of EM pathogenesis.

Previous studies have shown that α-linolenic acid (ALA) has a significant regulatory effect on related disorders induced by high-fat diets (HFDs), but little is known regarding the correlation between the gut microbiota and disease-related multitissue homeostasis. We systematically investigated the effects of ALA on the body composition, glucose homeostasis, hyperlipidemia, metabolic endotoxemia and systemic inflammation, white adipose tissue (WAT) homeostasis, liver homeostasis, intestinal homeostasis, and gut microbiota of mice fed an HFD (HFD mice). We found that ALA improved HFD-induced multitissue metabolic disorders and gut microbiota disorders to various degrees. Importantly, we established a complex but clear network between the gut microbiota and host parameters. Several specific differential bacteria were significantly associated with improved host parameters. Rikenellaceae_RC9_gut_group and Parasutterella were positively correlated with HFD-induced “harmful indicators” and negatively correlated with “beneficial indicators.” Intriguingly, Bilophila showed a strong negative correlation with HFD-induced multitissue metabolic disorders and a significant positive correlation with most beneficial indicators, which is different from its previous characterization as a “potentially harmful genus.” Turicibacter might be the key beneficial bacterium for ALA-improved metabolic endotoxemia, while Blautia might play an important role in ALA-improved gut barrier integrity and anti-inflammatory effects. The results suggested that the gut microbiota, especially some specific bacteria, played an important role in the process of ALA-improved multitissue homeostasis in HFD mice, and different bacteria might have different divisions of regulation. IMPORTANCE Insufficient intake of n-3 polyunsaturated fatty acids is an important issue in modern Western-style diets. A large amount of evidence now suggests that a balanced intestinal microecology is considered an important part of health. Our results show that α-linolenic acid administration significantly improved the host metabolic phenotype and gut microbiota of mice fed a high-fat diet, and there was a correlation between the improved gut microbiota and metabolic phenotype. Some specific bacteria may play a unique regulatory role. Here, we have established correlation networks between gut microbiota and multitissue homeostasis, which may provide a new basis for further elucidating the relationship between the gut microbiota and host metabolism.

Background: Alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30) derived from Momordica charantia L. have been confirmed to possess antitumor and antivirus activities due to their RNA-N-glycosidase activity. However, strong immunogenicity and short plasma half-life limit their clinical application. To solve this problem, the two proteins were modified with (mPEG) 2 -Lys-NHS (20 kDa). Methodology/principal findings: In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs), α-MMC and MAP30, was successfully developed for laboratory-scale preparation. Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds. The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N-terminal sequence analysis as well as Western blot. Two polyethylene glycol (PEG)ylated proteins were synthesized and purified. Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex virus-1. Furthermore, both PEGylated proteins showed about 60%-70% antitumor and antivirus activities, and at the same time decreased 50%-70% immunogenicity when compared with their unmodified counterparts. Conclusion/significance: α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with nanomaterials to be a targeting drug that can further decrease immunogenicity and side effects. Through nanotechnology we can make them low-release drugs, which can further prolong their half-life period in the human body.

Laryngeal squamous cell carcinoma (LSCC) is one of the most commonly diagnosed malignancies with high occurrence of tumor metastasis, which usually exposes to fluid shear stress (FSS) in lymphatic channel and blood vessel. Epithelial-mesenchymal transition (EMT) is an important mechanism that induces metastasis and invasion of tumors. We hypothesized that FSS induced a progression of EMT in laryngeal squamous carcinoma. Accordingly, the Hep-2 cells were exposed to 1.4 dyn/cm2 FSS for different durations. Our results showed that most of cells changed their morphology from polygon to elongated spindle with well-organized F-actin and abundant lamellipodia/filopodia in protrusions. After removing the FSS, cells gradually recovered their flat polygon morphology. FSS induced Hep-2 cells to enhance their migration capacity in a time-dependent manner. In addition, FSS down-regulated E-cadherin, and simultaneously up-regulated N-cadherin, translocated β-catenin into the nucleus. These results confirmed that FSS induced the EMT in Hep-2 cells, and revealed a reversible mesenchymal-epithelial transition (MET) process when FSS was removed. We further examined the time-expressions of signaling cascades, and demonstrated that FSS induces the EMT and enhances cell migration depending on integrin-ILK/PI3K-AKT-Snail signaling events. The current study suggests that FSS, an important biophysical factor in tumor microenvironment, is a potential determinant of cell behavior and function regulation.

BackgroundThe marginal division of neostriatum (MrD) is a flat, pan-shaped zone between the neostriatum and the globus pallidus, and previous documents demonstrated that it was involved in the modulation of pain. The aim of this study is to investigate the roles of the MrD of the human brain in the chronicization migraine using resting state functional magnetic resonance imaging (rs-fMRI).MethodsConventional MRI, 3D structure images, and rs-fMRI were performed in 18 patients with episodic migraines (EM), 16 patients with chronic migraine (CM), 44 patients with medication overuse headache plus chronic migraine (MOH + CM), and 32 normal controls (NC). MrD was defined using manual delineation on structural images, and was selected as the seed to calculate the functional connectivity (FC).ResultsCompared with the NC group, the decreased FC of MrD was observed in the EM and CM groups, and increased FC of MrD was demonstrated in all patient groups. Compared with the EM group, the decreased FC of MrD was revealed in the CM and MOH + CM groups, and the increased FC occurred only in the CM group. Increased FC of MrD alone was observed in the MOH + CM group compared with that in the CM group.ConclusionThis study confirmed the double neuromodulation network of MrD in pain modulation and migraine chronicization; however, the mechanism requires further investigation.

As China undergoes urbanization, lifestyles and disease profiles are changing. In this study, metabolic syndrome (MetS) was discovered in 53.5% and 42.7% of men and women, respectively. In 3 age cohorts (44, 48, and 52 years), prevalence of MetS among women was 33.3%, 41.4%, and 50.8%, respectively (χ2 = 10.27, P = .006), whereas among men it was 51.5%, 56.3%, and 52.3%, respectively (χ2 = 0.46, P = .796). The component contributing to the presence of MetS was increased waist circumference, especially among women. MetS among men results from higher rates of elevated triglycerides, blood pressure, and blood glucose when compared with women. Risk factors for MetS included less than 60 minutes of exercise a week (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.4) and rarely consuming milk (OR = 1.7, 95% CI = 1.2-2.3). Abstaining from or occasionally consuming alcohol (OR = 0.7, 95% CI = 0.4-1.1) and having parents with no chronic disease (OR = 0.4, 95% CI = 0.2-0.6) suggest increased protection against MetS.

BackgroundPeriaqueductal gray (PAG) is a substantial descending pain modulatory center, and previous voxel-based morphometry study confirmed the clusters with increased volume in PAG region in medication-overuse headache (MOH). The aim of this study is to investigate altered PAG volume in MOH using an automated PAG segment method to measure the true PAG volume.MethodsHigh resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 22 patients with MOH and 22 normal controls (NC). PAG template was created based on ICBM 152 gray template, and the individual PAG was generated by applying the deformation field from structural image segment to the PAG template, and individual PAG volume was calculated.ResultsThere was a significant increased volume of PAG in MOH (0.366 ± 0.005 ml) than that in NC (0.341 ± 0.005 ml)(P < 0.05). There was no significant correlation between the PAG volume and the clinical variables in MOH patients (P > 0.05). The area of receiver operating characteristic (ROC) curve was 0.845, and the cut-off of PAG volume was 0.341 ml with sensitivity 95.5% and specificity 63.6%.ConclusionThe present study demonstrated that the PAG volume gain was confirmed in MOH patients, and the automated individual PAG volume measure may be considered as a simple and effective imaging biomarker in MOH diagnosis.

BackgroundThe periaqueductal gray (PAG) dysfunction was recognized in migraine, and the nonspecific PAG lesions were also observed in episodic migraine (EM) recently. However, the PAG volume change was not totally detected in EM up to now. Herein, the aim of this study was to investigate altered PAG volume in EM patients based on high resolution brain structural image.MethodsThe brain structural images were obtained from 18 normal controls (NC), 18 EM patients and 16 chronic migraine (CM) on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template using MRIcron, and the individual PAG was created by applying the deformation field to the PAG template after structural image segment. One-way analysis of covariance, partial correlation analysis and Receiver operating characteristics (ROC) curve were applied.ResultsEM had a larger PAG volume (0.35 ± 0.02 ml) than that (0.32 ± 0.02 ml) of NC (P = 0.017). The PAG volume of CM (0.33 ± 0.02 ml) was negatively related to the VAS score (P = 0.03). ROC analysis demonstrated that PAG volume has higher diagnostic efficacy (AUC, 0.731; Sensitivity, 0.556; Specificity, 0.889) for NC vs. EM compared with that NC vs. CM (AUC, 0.634; Sensitivity, 0.438; Specificity, 0.833) and EM vs. CM (AUC, 0.618; Sensitivity, 0.813; Specificity, 0.556).ConclusionPAG volume expansion may be the direct impairment evidence on the brain in EM, and could be considered as a diagnostic and evaluated imaging biomarker in migraine.