Lycium barbarum polysaccharide-glycoprotein preventative treatment ameliorates aversive.

Previous studies have shown that Lycium barbarum polysaccharide, the main active component of Lycium barbarum, exhibits anti-inflammatory and antioxidant effects in treating neurological diseases. However, the therapeutic action of Lycium barbarum polysaccharide on depression has not been studied. In this investigation, we established mouse models of depression using aversive stimuli including exposure to fox urine, air puff and foot shock and physical restraint. Concurrently, we administered 5 mg/kg per day Lycium barbarum polysaccharide-glycoprotein to each mouse intragastrically for the 28 days. Our results showed that long-term exposure to aversive stimuli significantly enhanced depressive-like behavior evaluated by the sucrose preference test and the forced swimming test and increased anxiety-like behaviors evaluated using the open field test. In addition, aversive stimuli-induced depressed mice exhibited aberrant neuronal activity in the lateral habenula. Importantly, concurrent Lycium barbarum polysaccharide-glycoprotein treatment significantly reduced these changes. These findings suggest that Lycium barbarum polysaccharide-glycoprotein is a potential preventative intervention for depression and may act by preventing aberrant neuronal activity and microglial activation in the lateral habenula. The study was approved by the Jinan University Institutional Animal Care and Use Committee (approval No. 20170301003) on March 1, 2017.

MMP-9, Vertebrobasilar Ectasia and Vertebral Artery Dominance in Vertigo or Dizziness Patients With Vascular Risk Factors.

Background and Purpose: Although vertebrobasilar ectasia (VBE) is diagnosed with increasing frequency, it is not clear whether this is because of altered hemodynamics caused by the effects of matrix metalloproteinases (MMPs) and/or vertebral artery dominance (VAD). Therefore, we investigate the relationship between plasma levels of MMPs and VBE in patients with vertigo or dizziness who also have vascular risk factors, in order to determine whether high levels of MMPs in VBE are independent of VAD. Methods: We prospectively studied 285 patients with vertigo or dizziness and at least one vascular risk factor. Plasma levels of MMPs, tissue inhibitor of metalloproteinases (TIMPs) and cathepsin L were measured. Subjects were classified as VBE-negative or VBE-positive, who were further classified based on the presence of VAD with magnetic resonance angiography. Acute ischemic stroke was screened by diffusion-weighted imaging, generally after bedside evaluation and the drawing of blood samples. Receiver operating characteristic (ROC) curves were applied to evaluate the utility of these potential biomarkers in predicting risk for ischemic stroke. Results: The prevalence of VBE in patients with vertigo or dizziness was 16.5%. Of the 82 patients with ischemic stroke, 14 strokes involved the cortex or subcortex. MMP-9 levels were significantly higher in the VBE-positive group than in the VBE-negative group (P = 0.022). There was a significant difference in the risk of posterior circulation ischemic stroke between the VBE-positive group and the VBE-negative group (P = 0.002). Levels of MMP-2 and cathepsin L tended to be higher in the VBE-negative group (P = 0.054, P = 0.060, respectively). Compared with the non-VAD subgroup, levels of MMP-2,-3,-9, TIMP-1,-2, and cathepsin L were similar in the VAD subgroup. ROC analysis showed that MMP-9 predicted risk for ischemic stroke (AUC = 0.582, 95%CI, 0.510-0.654, P = 0.030). Conclusions: MMP-9 was associated with VBE and independent of VAD. High levels of MMP-9 may predict risk for ischemic stroke in patients with vertigo or dizziness who also have vascular risk factors.

Basilar Artery Tortuosity Is Associated With White Matter Hyperintensities by TIMP-1.

BACKGROUND AND PURPOSE: To test the hypothesis that the imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may play a potential role in bridging vertebrobasilar dolichoectasia (VBD) with lacunar infarction (LI) and white matter hyperintensities (WMH). METHODS: We studied 212 patients with vertigo who underwent multimodal magnetic resonance imaging (MRI) tests for VBD, LI, and WMH identification. We investigated biomarkers of VBD with magnetic resonance angiography (MRA) via various physical characteristics of the vertebrobasilar arteries (VBAs). Similarly, LI and WMH biomarkers were extracted using T2-weighted and fluid attenuated inversion recovery (FLAIR) images. We first determined which of these neuroimaging markers were significant identifiers of VBD, LI and the different grades of WMH. We then sought to draw potential mechanistic conclusions from these MRI-derived parameters, by associating the aforementioned biomarkers with MMP and TIMP serum levels in patient blood samples using non-parametric statistical tests. RESULTS: MMP-9 serum level was significantly higher in vertigo patients with VBAs dilation and basilar artery (BA) elongation compared to those with healthy arterial size, and the ratio of MMP-9/TIMP-1 level were higher in those patients. TIMP-1 level was also markedly higher in vertigo patients with BA tortuosity than those without BA tortuosity. The bending length (BL) of the BA was positively correlated with TIMP-1. The length, BL, and tortuosity index of the BA, as well as serum levels of TIMP-1 were greater in patients with higher WMH grades compared to those with low WMH grades. The vertebral artery and BA diameters, and the levels of MMP-2, -3, -9, TIMP-2 and cathepsin L were similar in patients with different WMH grades. CONCLUSION: In vertigo patients, we found various probably associations between MMP-9 and TIMP-1 with arterial alterations linked to both VBD and WMH that may help with the diagnosis and treatment of such diseases in the future.

Prevalence of Stroke and Hypoperfusion in Patients With Isolated Vertigo and Vascular Risk Factors.

Background and Purpose: The aim of this study was to determine the prevalence and associated factors of stroke and hypoperfusion among patients with isolated vertigo and vascular risk factors. Methods: We studied 157 patients with isolated vertigo who had undergone multimodal magnetic resonance imaging. Magnetic resonance angiography (MRA) was used to measure the diameters of vertebrobasilar arteries and to evaluate morphologic changes to vessels. Measurements obtained included length of the basilar artery and curvature index for the vertebral artery (VA). Perfusion-weighted imaging (PWI) was performed to determine relative cerebral blood flow, relative cerebral blood volume (rCBV), time to peak (TTP), and mean transit time for two mirror regions of interest (ROIs) in each map. Regional hypoperfusion of the cerebellum was considered significant when TTP and mean transit time (MTT) were present in ≥2 adjacent slices. Results: The prevalence of stroke in patients with isolated vertigo and vascular risk factors was 24.8% (n = 39). Visual assessment revealed cerebellar hypoperfusion in 57.6% (68/118) of non-stroke patients. Multivariate logistic regression indicated that diabetes mellitus (P = 0.049, OR = 2.758), VA stenosis or hypoplasia (P = 0.023, OR = 3.486), and relative TTP of cerebellum (P = 0.002, OR = 3.197) were independent risk factors for stroke and LVA curvature index (P = 0.026, OR = 2.049), VA stenosis and hypoplasia (P = 0.009, OR = 2.977) were independent risk factors for hypoperfusion. Conclusions: The prevalence of stroke and hypoperfusion is higher in patients with isolated vertigo and vascular risk factors, compared with matched controls. Potential risk factors include diabetes mellitus, VA stenosis or hypoplasia, and enlarged VA curvature index.

Perfusion by delayed time to peak in vertebrobasilar dolichoectasia patients with vertigo.

OBJECTIVE: To investigate the association between the perfusion magnetic resonance imaging (MRI) and vertebrobasilar dolichoectasia (VBD) in vertigo patients and at least one vascular risk factor. METHODS: We studied 289 patients with vertigo (spinning, swaying, nausea, vomiting, and unsteady gait) who performed multimode MRI. Maximum diameter and tortuous parameters of the basilar artery and vertebral arteries were calculated using magnetic resonance angiography. Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), mean transit time (MTT), and time to peak (TTP) maps were evaluated by dynamic susceptibility contrast-enhanced perfusion imaging. Association of perfusion MRI and VBD was evaluated by nonparametric tests and receiver-operating characteristic curve was constructed to predict posterior ischemic stroke in VBD patients. RESULTS: The prevalence of VBD was 26.6% (n = 77/289) in our study. Male gender was the risk factor of VBD by multivariate analysis. BA diameter was significant statistics between ischemic stroke and nonischemic stroke patients. TTP in bilateral lower cerebellum, superior cerebellum, bilateral pons, and occipital and temporal lobes region of interests was significantly delayed in VBD versus non-VBD patients, while rCBF, rCBV, and MTT parameters were not significant differences. TTP in the right temporal lobe delayed by 21.96 ms was the best predictive value and the mean TTP predictive threshold value in all ROIs was 22.67 ± 1.48 ms. INTERPRETATION: VBD leads to the hypoperfusion of posterior circulation territory characterized by delayed TTP. Delayed TTP in cerebellum, pons, and occipital and temporal lobes fed by vertebrobasilar arteries predicted the occurrence of posterior ischemic stroke in VBD patients.

Why does my patient's basilar artery continue to grow? A four-year case study of a patient with symptoms of vertebrobasilar dolichoectasia.

BACKGROUND: Vertebrobasilar dolichoectasia (VBD) is a clinical entity associated with ischemic stroke, compression of cranial nerves or brainstem, and hydrocephalus. There have been relatively few studies following the progression of VBD in patients presenting with a variety of diverse clinical features. CASE PRESENTATION: Here, we report a case study of a male with progressive VBD who was followed from November 2012 to December 2016. The patient had diagnosed hypertension for several years and suffered from left peripheral facial paralysis, recurrent ischemic attacks in the brainstem and cerebellum, obstructive hydrocephalus and frequent pneumonia. A series of cranial CT and multi-modal MRI scans were performed to explore the brain imaging features of the patient during follow-up. CONCLUSIONS: The presented case study suggests that aging, uncontrolled hypertension, arterial dissection and infection may contribute to the exacerbation of VBD and recurrent ischemic stroke.

[NIR Assignment of Magnolol by 2D-COS Technology and Model Application Huoxiangzhengqi Oral Liduid].

Near infrared (NIR) spectroscopy assignment of Magnolol was performed using deuterated chloroform solvent and two-dimensional correlation spectroscopy (2D-COS) technology. According to the synchronous spectra of deuterated chloroform solvent and Magnolol, 1365~1455, 1600~1720, 2000~2181 and 2275~2465 nm were the characteristic absorption of Magnolol. Connected with the structure of Magnolol, 1440 nm was the stretching vibration of phenolic group O-H, 1679 nm was the stretching vibration of aryl and methyl which connected with aryl, 2117, 2304, 2339 and 2370 nm were the combination of the stretching vibration, bending vibration and deformation vibration for aryl C-H, 2445 nm were the bending vibration of methyl which linked with aryl group, these bands attribut to the characteristics of Magnolol. Huoxiangzhengqi Oral Liduid was adopted to study the Magnolol, the characteristic band by spectral assignment and the band by interval Partial Least Squares (iPLS) and Synergy interval Partial Least Squares (SiPLS) were used to establish Partial Least Squares (PLS) quantitative model, the coefficient of determination Rcal(2) and Rpre(2) were greater than 0.99, the Root Mean of Square Error of Calibration (RM-SEC), Root Mean of Square Error of Cross Validation (RMSECV) and Root Mean of Square Error of Prediction (RMSEP) were very small. It indicated that the characteristic band by spectral assignment has the same results with the Chemometrics in PLS model. It provided a reference for NIR spectral assignment of chemical compositions in Chinese Materia Medica, and the band filters of NIR were interpreted.

Targeted metabolomic study indicating glycyrrhizin's protection against acetaminophen-induced liver damage through reversing fatty acid metabolism.

The present study aimed to give a short report on a possible mechanism of glycyrrhizin to acetaminophen-induced liver toxicity. Seven-day intraperitoneal administration of glycyrrhizin (400 mg/kg/day) to 2- to 3-month-old male C57BL/6N mice (mean weight 27 g) significantly prevents acetaminophen-induced liver damage, as indicated by the activity of alanine transaminase and aspartate aminotransferase. Metabolomics analysis and principal component analysis (PCA) using ultra-fast liquid chromatography coupled to triple time-of-flight mass spectrometer were performed. PCA separated well the control, glycyrrhizin-treated, acetaminophen-treated, and glycyrrhizin+acetaminophen-treated groups. Long-chain acylcarnitines were listed as the top ions that contribute to this good separation, which include oleoylcarnitine, palmitoylcarnitine, palmitoleoylcarnitine, and myristoylcarnitine. The treatment of glycyrrhizin significantly reversed the increased levels of long-chain acylcarnitines induced by acetaminophen administration. In conclusion, this metabolomic study indicates a significant glycyrrhizin protection effect against acetaminophen-induced liver damage through reversing fatty acid metabolism.

[Multivariate detection limits of baicalin in qingkailing injection based on four NIR spectrometer types].

Multivariate detection limits (MDLs) of different types of near-infrared instruments were investigated to guide the selection of device type for TCM NIR analysis. In this paper, near-infrared spectroscopy of Qingkailing injection was performed in transmission mode on four near-infrared spectrometers named a, b, c and d, respectively. High performance liquid chromatography (HPLC) was used as the reference method to determine the content of baicalin in Qingkailing injection. Partial least squares (PLS) and interval partial least squares (iPLS) quantitative models of baicalin in Qingkailing injection were established and MDLs of quantitative models based on different types of instruments were calculated. The determination coefficient of prediction (R2(pre))and the root mean square errors of prediction (SEP) of PLS models of four different near-infrared spectrometers are 0.9762 and 230.4 microg x mL(-1) (a), 0.9561 and 246.4 microg x mL(-1) (b), 0.9662 and 264.4 microg x mL*-1) (c), 0.9985 and 71.5 microg x mL(-1) (d). And the model of instrument d shows a better prediction performance than the other three types. There are no remarkable superiorities in predictability in iPLS models of instruments a and b after variable selection, since the R2(pre) and SEP values for instruments a and b are 0.9771 and 218.4 microg x mL(-1), and 0.9754 and 219.4 microg x mL(-1), respectively. Models c and d show no results of variable selection. MDLs (delta(0.05, 0.05) of different instruments are all less than 250 microg x mL(-1), and the MDLs of instruments c and d reach to 58 and 2.9 microg x mL(-1) respectively. The results reveal that the predictability of models and corresponding MDLs are different for different detection equipments. This paper innovatively used the theory of MDL to investigate the detection performance of different types of NIR instruments. The results demonstrated the feasibility of the approach. And it is expected that in actual applications, choosing the right type of instrument should be based on the characteristics of the study carrier to ensure quantitative accuracy.