Local white matter abnormalities in Parkinson's disease with mild cognitive impairment: Assessed with neurite orientation dispersion and density imaging.

Mild cognitive impairment is a nonmotor complication in Parkinson's disease (PD) that have a high risk of developing dementia. White matter is associated with cognitive function in PD and the alterations may occur before the symptoms of the disease. Previous diffusion tensor imaging (DTI) studies lacked specificity to characterize the concrete contributions of distinct white matter tissue properties. This may lead to inconsistent conclusions about the alteration of white matter microstructure. Here, we used neurite orientation dispersion and density imaging (NODDI) and white matter fiber clustering method to uncover local white matter microstructures in PD with mild cognitive impairment (PD-MCI). This study included 23 PD-MCI and 20 PD with normal cognition (PD-NC) and 21 healthy controls (HC). To probe specific and fine-grained differences, metrics of NODDI and DTI in white matter fiber clusters were evaluated using along-tract analysis. Our results showed that PD-MCI patients had significantly lower neurite density index (NDI) and orientation dispersion index (ODI) in white matter fiber clusters in the prefrontal region. Correlation analysis and receiver operating characteristic (ROC) analysis revealed that the diagnostic performance of NODDI-derived metrics in cingulum bundle (2 clusters) and thalamo-frontal (2 clusters) were superior to DTI metrics. Our study provides a more specific insight to uncover local white matter abnormalities in PD-MCI, which benefit understanding the underlying mechanism of cognitive decline in PD and predicting the disease in advance.

Astragaloside IV reverses MNNG-induced precancerous lesions of gastric carcinoma in rats: Regulation on glycolysis through miRNA-34a/LDHA pathway.

This study was designed to investigate the precancerous lesions of gastric carcinoma (PLGC)-reversing mechanisms of astragaloside IV (ASIV) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced PLGC rats. All rats were sacrificed after 10-week treatment. Gastric tissue was analyzed by using histopathology and electron microscope. To be fully evidenced, LDHA, p53, TIGAR, MCT1, MCT4, HIF-1α, CD147, and miRNA-34a were detected by Western blotting and Real-time Quantitative polymerase chain reaction (RT-qPCR). As histopathology and electron microscope showed, it can be clearly observed that the area of dysplasia was reduced in ASIV groups, indicating that MNNG-induced PLGC was markedly reversed by ASIV. Moreover, compared with model group, a significant decrease in gene expressions of LDHA, MCT1, MCT4, HIF-1α, CD147, and TIGAR was observed whereas miRNA-34a level was increased in ASIV groups. A significant up-regulation induced by MNNG in protein levels of LDHA, MCT1, MCT4, HIF-1α, and CD147 was attenuated in rats treated with ASIV. In contrast, the decreased expression of TIGAR was restored by ASIV. Interestingly, up-regulation of p53 expression induced by MNNG was further increased in ASIV groups. In brief, these results implied that abnormal glycolysis was relieved by ASIV via regulation of the expressions of LDHA, p53, TIGAR, MCT1, MCT4, HIF-1α, CD147, and miRNA-34a.

Selective reduction in the expression of UGTs and SULTs, a novel mechanism by which piperine enhances the bioavailability of curcumin in rat.

Curcumin (CUR) is known to exert numerous health-promoting effects in pharmacological studies, but its low bioavailability hinders the development of curcumin as a feasible therapeutic agent. Piperine (PIP) has been reported to enhance the bioavailability of curcumin, but the underlying mechanism remains poorly understood. In an attempt to find the mechanism by which piperine enhances the bioavailability of curcumin, the dosage ratio (CUR: PIP) and pre-treatment with piperine were hypothesized as key factors for improving the bioavailability in this combination. Therefore, combining curcumin with piperine at various dose ratios (1:1 to 100:1) and pre-dosing with piperine (0.5-8 h prior to curcumin) were designed to investigate their contributions to the pharmacokinetic parameters of curcumin in rats and their effects on the expression of UGT and SULT isoforms. It was shown that the Cmax and AUC0-t of curcumin were slightly increased by 1.29 and 1.67 fold at a ratio of 20:1, while curcumin exposure was enhanced significantly in all the piperine pre-treated rats (0.5-8 h), peaking at 6 h (a 6.09-fold and 5.97-fold increase in Cmax and AUC0-t , p < 0.01), regardless of the unchanged t1/2 and Tmax . Also observed was a time-dependent inhibition of the hepatic expression of UGT1A6, 1A8, SULT1A1, 1A3, and the colonic expression of UGT1A6 that occurred within 6 h of piperine pre-treatment but was reversed at 8 h, which correlated with the changes in curcumin exposure. Similarly, the inhibitory effect of piperine on most of the UGTs and SULTs are time-dependent in Caco-2 and HepG2 cells. It is concluded that piperine pre-treatment time-dependently improves the bioavailability of curcumin through the reversible and selective inhibition of UGTs and SULTs. Copyright © 2016 John Wiley & Sons, Ltd.

Investigation into white matter microstructure differences in visual training by using an automated fiber tract subclassification segmentation quantification method.

Visual training has emerged as a useful framework for investigating training-related brain plasticity, a highly complex task involving the interaction of visual orientation, attention, reasoning, and cognitive functions. However, the effects of long-term visual training on microstructural changes within white matter (WM) is poorly understood. Therefore, a set of visual training programs was designed, and automated fiber tract subclassification segmentation quantification based on diffusion magnetic resonance imaging was performed to obtain the anatomical changes in the brains of visual trainees. First, 40 healthy matched participants were randomly assigned to the training group or the control group. The training group underwent 10 consecutive weeks of visual training. Then, the fiber tracts of the subjects were automatically identified and further classified into fiber clusters to determine the differences between the two groups on a detailed scale. Next, each fiber cluster was divided into segments that can analyze specific areas of a fiber cluster. Lastly, the diffusion metrics of the two groups were comparatively analyzed to delineate the effects of visual training on WM microstructure. Our results showed that there were significant differences in the fiber clusters of the cingulate bundle, thalamus frontal, uncinate fasciculus, and corpus callosum between the training group compared and the control group. In addition, the training group exhibited lower mean fractional anisotropy, higher mean diffusivity and radial diffusivity than the control group. Therefore, the long-term cognitive activities, such as visual training, may systematically influence the WM properties of cognition, attention, memory, and processing speed.

Fiber-specific white matter alterations in Parkinson's disease patients with freezing of gait.

Freezing of gait (FOG) is a gait disorder that usually occurs in advanced stages of Parkinson's disease (PD). Understanding the underlying mechanism of FOG is important for treatment and prevention. Previous studies have investigated white matter (WM) structure to explore the pathology of FOG. However, the pathology is still unclear, possibly due to the methodological limitation in identifying specific fiber tracts. This study aimed to investigate tract-specific WM structural changes in FOG patients and their relationships with clinical characteristics. We enrolled 19 PD patients with FOG (PD-FOG), 19 without FOG (PD-woFOG) and 21 controls. Fixel-based analysis is a novel framework to avoid the effect of crossing fibers, which provides the metrics to assess WM morphology. By combining a method for segmenting fibers, we identified abnormalities in the specific fiber tracts. Compared to PD-woFOG, PD-FOG showed significant increased fiber-bundle cross-section (FC) in the corpus callosum (CC), fornix (FX), inferior longitudinal fasciculus (ILF), striato-premotor (ST_PREM), superior thalamic radiation (STR), thalamo-premotor (T_PREM), increased fiber density and cross-section (FDC) in the STR, and decreased fiber density (FD) in the CC and ILF. Additionally, the ILF was correlated with motor, cognition and memory, the CC was correlated with anxiety, and the T_PREM was also correlated with cognition. In conclusion, in addition to impairments of WM found in PD-FOG, we found enhancements in WM, which may imply compensatory mechanisms. Furthermore, multiple fiber tracts were correlated with clinical characteristics, especially the ILF, validating the involvement of transmission circuits of multiple distinct information in mechanisms of FOG.

Alterations in white matter fiber in Parkinson disease across different cognitive stages.

Cognitive impairment in Parkinson disease (PD) leads to substantial disability. Unlike external manifestations such as tremor, the decay of cognitive function is often an underlying process, and its neuroanatomic substrates are not yet fully elucidated. Knowledge regarding cognitive-related alterations in white matter (WM) pathways helps us understand the mechanisms of cognitive decline in patients with PD. Previous voxel-based analyses with Diffusion tensor imaging (DTI) metrics, such as fractional anisotropy (FA) and mean diffusivity (MD) have uncovered white matter differences in groupwise, but the conclusions were inconsistent. That was partially due to white matter fibers that are known to affect cognition, such as the corpus callosum (CC) and superior longitudinal fasciculus that cross in voxel, and are hard to interpreted by the abovementioned metrics. Furthermore, cognitive decay is a continuous process, it is difficult to reflect the continuous changes of white matter fibers between groups comparison. In the present work, we chose the constrained spherical deconvolution (CSD) and the fixel model, which avoided the effect of crossing fibers. To compare the white matter fiber in different cognitive stages of patients with PD, the results found that the CC, the cingulum bundle (CB), and the corticospinal tract (CST) showed the same trend in the decline of cognitive function, and this change may lead to the impairment of cognitive function. Our findings can help physicians determine the cognitive stage of PD from the perspective of white matter fiber and provide a reference for clinical trials and predictions.

[Clinical study on improving the strength and activity of lumbar spine with Qiang Jin exercises].

OBJECTIVE: To observe the effect of Qiang Jin exercises on the muscle strength and activity of lumbar spine in patients with lumbar disc herniation. METHODS: From March 2016 to September 2017, at the Department of Orthopaedics, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, a total of 110 subjects were enrolled, and 98 eligible subjects were screened. The subjects were randomized by stratified randomization and divided into experimental group and control group, 49 cases in each group, 25 males and 24 females in the experimental group, 25 males and 24 females in the control group. The experimental group exercised with Qiang Jin exercises, one time each morning and evening, each time10 sets were made;the control group used classic rehabilitation training, training twice a week, and three months was a course of treatment. After 12 weeks of training, the muscle strength and activity of the lumbar spine were evaluated and compared with the muscle strength and activity of the lumbar spine before training. RESULTS: The experimental group and the control group had different muscle strength and activity of the lumbar spine before and after treatment (P<0.05). There was no significant difference between two groups after treatment(P>0.05). CONCLUSION: Qiang Jin exercises can effectively improve the muscle strength and activity of the lumbar spine and improve the daily living ability of patients.

[Imaging study of lumbosacral multifidus muscle fat changes in patients with lumbar disc herniation].

OBJECTIVE: To compare the degeneration of lumbosacral multifidus muscle in patients with lumbar disc herniation. METHODS: Magnetic Resonance Spectroscopy was performed on the multifidus muscle of 35 healthy volunteers and 35 patients with unilateral L4,5 lumbar disc herniation. There were 20 males and 15 females in each group, aged from 25 to 55 years old. In healthy volunteers, the mean age was (35.66±8.73) years old and the BMI was (21.85±1.94) kg/m2; in the patients, the mean age was (36.09±7.70) years old, the BMI was (21.50±1.78) kg/m2, the VAS score was (4.40±0.88) points, the course of disease was (11.2±7.14) months. The proportion of fat in the L4,5 lumbosacral multifidus muscle and the proportion of fat-suppressed cross-sectional area were observed by MRI, the differences of the observation indexes of the two groups were compared through data analysis. RESULTS: In healthy volunteers, the proportion of fat on the left side of the multifidus muscle was (0.169± 0.035)%, the proportion of fat removal cross-sectional area on the left side of the multifidus muscle was (0.699±0.070)%, the proportion of fat on the right side of the multifidus muscle was (0.168±0.031)%, and the proportion of fat removal cross-sectional area on the right side of the multifidus muscle was (0.712±0.056)%, there was no significant difference between the two sides (P>0.05). In patients, the proportion of fat on the healthy side of multifidus muscles was (0.173±0.021)%, the proportion of fat removal cross-sectional area on the healthy side of multifidus muscles was (0.695±0.054)%, the proportion of fat on the affected side of the multifidus muscle was (0.228±0.027)%, and the proportion of fat removal cross-sectional area on the affected side of the multifidus muscle was (0.629±0.048)%, the differences of the above indexes on both sides were statistically significant (P<0.05). There was a statistically significant difference in the proportion of multifidus muscle fat and the ratio of fat-suppressed cross-sectional area between the affected side and volunteers (P<0.05). There was no significant difference in fat ratio and fat-suppressed cross sectional area ratio between the left and right sides of healthy volunteers and healthy side of patients (P>0.05). CONCLUSION: There is degeneration of lumbosacral multifidus muscle on the affected side of patients with unilateral L4,5 intervertebral disc herniation, featuring multifidus muscular atrophy and fat infiltration.

[A comparative study on the surface electromyography of lumbosacral multifidus muscle in patients with lumbar disc herniation].

OBJECTIVE: To compare the degeneration of lumbosacral multifidus muscle in patients with lumbar disc herniation. METHODS: Thirty-five healthy volunteers and 35 patients with unilateral L4,5 lumbar disc herniation from December 2015 to September 2017 were recruited. There were 20 males and 15 females in each group, aged from 25 to 55 years old. In healthy volunteers group, the mean age was (35.66±8.73) years old and the BMI was (21.85±1.94) kg /m2. In patients with lumbar disc herniation, the mean age was (36.09±7.70) years old, the BMI was (21.50±1.78) kg /m2, the VAS score was 4.40±0.88, the course of disease was (11.20±7.14) months. Surface electromyography analysis was performed on the multifidus muscle of the two groups. The average myoelectric amplitude of the multifidus muscle in the two groups were compared. RESULTS: The average myoelectric amplitude of the multifidus muscle of healthy volunteers was (48.84±7.77) µV on the left and (49.13±7.86) µV on the right. There was no significant difference between the two sides (P>0.05). The average myoelectric amplitude of multifidus muscle in patients with lumbar disc herniation was(48.82±8.14) µV on the healthy side and (42.81±7.00) µV on the affected side, and the difference was statistically significant between two sides(P<0.05). There was no significant difference in the average myoelectric amplitude of multifidus muscle between the healthy side of lumbar disc herniation and on the left of healthy volunteers, or between the healthy side of lumbar disc herniation and on the right of healthy volunteers (P>0.05). There was significant difference in the average myoelectric amplitude of multifidus muscle between the affected side of lumbar disc herniation and on the left of healthy volunteers, and also between the affected side of lumbar disc herniation and on the right of healthy volunteers(P<0.05). CONCLUSION: Patients with chronic lumbar disc herniation have an imbalance in myoelectric activity, and the muscle strength of the multifidus muscle on the affected side is significantly reduced.

Surface chemical state evaluation of CoSe2 catalysts for the oxygen evolution reaction.

Orthorhombic CoSe2 catalysts with different surface structures and chemical states were tuned by precisely controlling the solvothermal synthesis temperature within a narrow range. The critical condition for efficient construction of metallic Co-Se bonds and its significance for the oxygen evolution reaction were demonstrated, which is instructive for selenide catalyst design and fabrication.

Protective effects of Weipixiao decoction against MNNG-induced gastric precancerous lesions in rats.

Gastric cancer is recognized as one of the most common cancer. In-depth research of gastric precancerous lesions (GPL) plays an important role in preventing the occurrence of gastric cancer. Meanwhile, traditional treatment provides a novel sight in the prevention of occurrence and development of gastric cancer. The current study was designed to assess the effects of therapy with Weipixiao (WPX) decoction on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL rats and the underlying molecular mechanisms. After 10-weeks treatment, all rats were sacrificed. Histopathological changes of gastric tissue were assessed via hematoxylin-eosin (HE) and High-iron diamine-Alcian blue-Periodic acid-Schiff (HID-AB-PAS) staining. To be fully evidenced, RT-qPCR, Western blot and immunohistochemistry were used to detect the expressions of LDHA, CD147, HIF-1α, MCT4, PI3K, AKT, mTOR and miRNA-34a, which were crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis. According to the results of HE and HID-AB-PAS staining, it could be confirmed that MNNG-induced GPL rats were obviously reversed by WPX decoction. Additionally, the increased gene levels of LDHA, CD147, MCT4, PI3K, AKT, mTOR and HIF-1α in model group were down-regulated by WPX decoction, while miRNA-34a expression was decreased and up-regulated by WPX decoction. The significantly increased protein levels of LDHA, CD147, MCT4, PI3K, AKT, mTOR and HIF-1α induced by MNNG were attenuated in rats treated with WPX decoction. In brief, the findings of this study imply that abnormal glycolysis in MNNG-induced GPL rats was relieved by WPX decoction via regulation of the expressions of LDHA, CD147, HIF-1α, MCT4, PI3K, AKT, mTOR and miRNA-34a.

Evaluation of type 2 diabetic mellitus animal models via interactions between insulin and mitogen­activated protein kinase signaling pathways induced by a high fat and sugar diet and streptozotocin.

Type 2 diabetic mellitus (T2DM), which is characterized by insulin resistance (IR), hyperglycemia and hyperlipidemia, is a comprehensive dysfunction of metabolism. The insulin receptor (INSR)/phosphoinositide 3­kinase (PI3K)/AKT signaling pathway is well acknowledged as a predominant pathway associated with glucose uptake; however, the effect of streptozotocin (STZ) plus a high fat and sugar diet (HFSD) on the proteins associated with this pathway requires further elucidation. In order to explore this effect, a T2DM rat model was constructed to investigate T2DM pathogenesis and potential therapeutic advantages. Rats were randomly divided into control and model groups, including normal diet (ND) and HFSD types. ND types were administered intraperitoneal (IP) injections of STZ (35 mg/kg) or a combination of STZ and alloxan monohydrate (AON) (40 mg/kg), whereas HFSD types were composed of HFSD pre­given, post­given and simul­given groups, and were modeled as follows: IP or intramuscular (IM) injection of STZ (35 mg/kg) or a combination of STZ and AON (40 mg/kg). Results indicated that, compared with controls, blood glucose, insulin, homeostatic model assessment­insulin resistance and total triglyceride were significantly elevated in groups with HFSD and modeling agents (P<0.05 or P<0.01), whereas total cholesterol and low­density lipoprotein levels were significantly elevated in groups simultaneously administered HFSD and modeling agents (P<0.05 or P<0.01), in addition to downregulation of the expression of insulin signaling pathway proteins in the liver, including INSR, PI3K, AKT1, phosphatidylinositol-5-phosphate 4­kinase type­2α (PIP5Kα) and glucose transporter (GLUT)2, and increased expression of inflammatory factors, including p38, tumor necrosis factor (TNF)α and interleukin (IL)6. Furthermore, compared with other two HFSD types including pre­given and post­given group, the simul­given group that received IM injection with STZ exhibited decreased expression levels of major insulin signal pathway proteins INSR, PI3K, AKT1, PIP5Kα, GLUT2 or GLUT4 in the liver and pancreas (P<0.05 or P<0.01), whereas the opposite was observed in the skeletal muscle. In addition, the protein expression levels of phosphorylated­p38, p38, IL6 and TNFα in the simul­given group that received IM injection with STZ were increased (P<0.05 or P<0.01), and histopathology also indicated inflammation in pancreas and liver. The present findings suggest that a low dose of STZ may partially impair the ß cells of the pancreas, whereas long­term excess intake of HFSD may increase lipid metabolites, inhibit the insulin signaling pathway and activate the mitogen­activated protein kinase p38 signaling pathway. The combined action of STZ and AON may result in insulin resistance, which ultimately results in abnormalities in glucose and lipid metabolism. The present model, analogue to T2DM onset of humans, evaluated the medical effect on metabolic dysfunction and provides an insight into the underlining mechanism of IR.

The gastric mucosal protective effects of astragaloside IV in mnng-induced GPL rats.

Gastric Cancer is one of the most common types of cancer. And the occurrence of gastric carcinoma is an evolutionary histopathological stage. As a result, further research of GPL, which is a borderline of gastric cancer, is indispensable for preventing the formation and development of gastric carcinoma. Several studies have demonstrated a correlation between the expression of autophagy, apoptosis and Gastric cancer (GC). However, the effects of autophagy and apoptosis on human gastric cancer progression, particularly on gastric precancerous lesions (GPL), have not totally been investigated. At present, Astragaloside IV(AS-IV) is a saponin purified from Astragalus membranaceous Bge, a traditional Chinese herb that has been widely used for more than 2000 y in the treatment of cancer, cardiovascular and immune disorders. This study was designed to investigate the mechanism of AS-IV protecting gastric mucosa in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL rats. The lesions of GIM and GED were significantly ameliorated compared with the model rats, especially crowded tubular glandular and back-to-back tubular structure, which were the dangerous borderline between GPL and GC. Western Blot analysis showed that the ratio of Bcl-2/Bax and the protein expression of Bcl-XL, p53, Beclin1, p62, ATG5 and ATG12 were decreased and the level of Caspase3 was increased in the group of AS-IV compared with the model group; RT-PCR analysis showed that the gene expression Ambra1, Beclin1, ATG5, LC3 and p62 were decreased in the group of AS-IV compared with the model group. This research manifested that the occurrence of gastric cancer was preceded by a prolonged precancerous stage, which could be ameliorated by the AS-IV. Meanwhile, the mild and moderate stage of precancerous lesions is similar with gastric adenocarcinoma in critical biological processes, including inflammation, cell proliferation, differentiation. But this lesion is very different from cancer, because it does not appear obvious invasion and malignant lesions in this pathologic stag. Further, AS-IV could regulate p53 expression to activate the Ambra1/Beclin1 complex in GPL, and it will protect the gastric mucosal injury, prevent and cure gastric mucosal atrophy, intestinal metaplasia and atypical hyperplastic lesions. It provided a potential therapeutic strategy in reversing intestinal metaplasia and dysplasia of gastric precancerous lesions and protecting the gastric mucosa in GPL rats.

Mechanism of YLTZ on glycolipid metabolism based on UPLC/TOF/MS metabolomics.

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by dysfunction of glycolipid metabolism. YLTZ is used to treat hyperlipidemia, yet its hypolipidemic and hypoglycemic mechanism on T2DM are unknown. Thus, UPLC/TOF/MS was applied in this study to identify the potential bio-markers, and deduce the possible metabolic pathways. According to bio-indexes, the increased blood lipid levels, including TC, TG, LDL and FA, and the decreased HDL, the elevated glucose, reduced insulin level and impaired OGTT were observed in diabetic rat model. While YLTZ can decrease the lipid levels and glucose content, as well as increased insulin standards and improve OGTT. After data from UPLC/TOF/MS processed, 17 metabolites were obtained, including phospholipids (LPCs, PCs and PGP (18:1)), beta-oxidation production (HAA, VAG and CNE) and precursors (THA), bile acid (CA, CDCA and IDCA), hydrolysate of TG (MG (22:4)), glycometabolism (G6P), cholesterol-driven synthetics (ADO) and production of arachidonate acid (THETA). As a result, YLTZ was able to reduce LPCs, PCs, PGP (18:1), HAA, VAG, CNE, CA, ADO and THETA, as well as enhance MG (22:4) and G6P. After analyzing results, several metabolic pathways were deduced, which containing, cholesterol synthesis and elimination, FA beta-oxidation, TG hydrolysis, phospholipids synthesis, glycolysis, gluconeogenesis and inflammation. Consequently, YLTZ performed to prohibit the FA beta-oxidation, synthesis of cholesterol and phospholipids, gluconeogenesis and inflammation level, as well as promote TG hydrolysis, glycolysis and blood circulation. Hence, applying metabonomics in TCM research can uncover its pharmacological edges, elucidating comprehensively that YLTZ has capacity of hypolipidemic, hypoglycemic and promoting blood circulation, matching the effect of removing blood stasis, eliminating phlegm and dampness.