OBJECTIVETo investigate the brain functional laterality in motor areas during motor execution systematically.

METHODSFunctional magnetic resonance imaging (fMRI) was employed combined with right hand sequential finger movement task to investigate brain activation pattern and laterality in 8 right-handed subjects. 3dDeconvolve program of AFNI was used to estimate the hemodynamic response function and to generate activation maps. Then the laterality index (LI) was calculated and tested statistically.

RESULTAll motor areas including the areas which were previously considered to be engage in movement preparation only were activated in movement execution. In the activation map, it appeared left lateralization in cerebra and right lateralization in cerebella. After further statistical test, it was found that in primary motor area (M1), supplementary motor area (SMA) and posterior parietal cortex (PPC), there were left lateralization. While in premotor cortex (PMC), cingulate gyrus and basal ganglia (BG), the lateralization tendency was not obvious. The activation in cerebella is characterized with right lateralization.

CONCLUSIONThough there are tiny differences among subjects, most of the motor areas appear lateralized activation. Past studies only observed laterality in several motor areas. It may be due to the difficulty of the task or the experimental design.

Adult ; Brain ; physiology ; Female ; Functional Laterality ; physiology ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Motor Cortex ; physiology

OBJECTIVETo investigate the effect of interferon regulatory factors (IRFs) on neointimal formation after vascular injury in the mouse, and its possible mechanism.

METHODSVascular injury was induced by polyethylene cuff placement around the left femoral artery of IRF-1-deficient mice and C57BL/6J mice. The mRNA expressions of IRF-1, IRF-2, angiotensin II type 2 (AT2) receptor, interleukin-1 beta converting enzyme (ICE), inducible nitric oxide synthase (iNOS) were detected by RT-PCR and immunohistochemical staining.

RESULTSNeointimal formation after vascular injury was significantly greater in IRF-1-deficient mice than that in C57BL/6J mice (P<0.05). In contrast, TUNEL-positive nuclei to total nuclei in the neointima and media in vascular smooth muscle cell (VSMC) in the injured artery significantly attenuated in IRF-1-deficient mice compared to C57BL/6J mice (P<0.05). The expressions of AT2 receptor as well as pro-apoptotic genes such as ICE and iNOS in C57BL/6J mice were up-regulated in response to vascular injury, but this upregulation was attenuated in IRF-1-deficient mice.

CONCLUSIONSOur results suggest that IRF-1 induces VSMC apoptosis and inhibits neointimal formation after vascular injury at least partly due to the upregulation of AT2 receptor, ICE and iNOS expressions. These results indicate that IRF-1 exerts an inhibitory effect on neointimal formation through the induction of apoptosis in VSMCs.

Animals ; Apoptosis ; physiology ; Caspase 1 ; genetics ; metabolism ; Femoral Artery ; anatomy & histology ; pathology ; Interferon Regulatory Factor-1 ; genetics ; metabolism ; Interferon Regulatory Factor-2 ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular ; cytology ; metabolism ; pathology ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Platelet Endothelial Cell Adhesion Molecule-1 ; genetics ; metabolism ; Receptor, Angiotensin, Type 2 ; genetics ; metabolism ; Tunica Intima ; pathology ; physiology

OBJECTIVETo detect the differences in subcortical structures between patients with paroxysmal kinesigenic dyskinesia (PKD) and normal subjects during movement preparation and execution.

METHODSThe PKD patients performed a movement task, in which a CUE signal (preparation) indicated the movement sequence prior to the appearance of an imperative GO signal (execution). Event-related functional magnetic resonance imaging (fMRI) and 3dDeconvolve program of AFNI were used to estimate the hemodynamic response function and to generate activation maps.

RESULTDuring movement preparation, the activated brain areas in PKD patients were less than those of normal subject, and there was no activation in basal ganglia in PKD patients. During execution, the activation was also less in PKD patients except in bilateral M1.

CONCLUSIONDuring intermission, abnormalities of the brain still exist in PKD patients when during preparing or performing movement. The movement circuit in the brain displays an unusual state. The attack may be caused by reducing of inhibition in brain areas.

Adult ; Chorea ; physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; Motor Cortex ; physiopathology ; Movement ; physiology

ObjectiveTo investigate the mechanism of Renshentang， recorded in Synopsis of Golden Chamber， in the treatment of atherosclerosis （AS） based on the autophagic effect of transient receptor potential vanilloid subtype 1 （TRPV1） on arterial smooth muscle. MethodFourteen SPF-grade 8-week-old male C57BL/6J mice were assigned to the normal group and 70 8-week-old apolipoprotein E knockout （ApoE^-/-） mice were assigned to the experimental group. The AS model was induced by a high-fat diet in the mice in the experimental group for eight weeks. The model mice were then randomly divided into model group， low-， medium-， and high-dose Renshentang groups （2.715， 5.43， and 10.68 g·kg^-1·d^-1）， and simvastatin group （0.02 g·kg^-1·d^-1）. Drug treatment lasted eight weeks. Serum was taken and serum total cholesterol （CHO）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured by assay kits to observe the changes in lipid levels in mice. The aorta was stained with hematoxylin-eosin （HE） to observe the overall pathology of the aortic root and oil red O staining was used to detect the lipid deposition in the aortic plaque and calculate the percentage of the aortic root area to the lumen area. The protein expression of TRPV1， adenylate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， autophagy effector-1 （Beclin-1）， and microtubule-associated protein 1 light chain 3 （LC3Ⅱ） in mouse aortic tissues was determined by Western blot. ResultCompared with the normal group， the model group showed increased serum CHO， TG， and LDL-C levels， decreased HDL-C， and increased aortic root plaque area （P<0.01）. Compared with the model group， the Renshentang groups showed decreased levels of CHO， TG， and LDL-C in serum （P<0.05， P<0.01）， especially in the low- and medium-dose Renshentang groups （P<0.01）. Compared with the normal group， the simvastatin group and the Renshentang groups showed reduced aortic root plaque area （P<0.05）， especially in the high-dose Renshentang group （P<0.01）. Compared with the normal group， the model group showed decreased relative expression levels of TRPV1， p-AMPK/AMPK， Beclin-1， and LC3Ⅱ/LC3Ⅰ（P<0.05， P<0.01）. Compared with the model group， the medium- and high-dose Renshentang groups showed increased relative expression levels of TRPV1， p-AMPK/AMPK， Beclin-1， and LC3Ⅱ/LC3Ⅰ（P<0.05，P<0.01）. ConclusionThe anti-AS effect of Renshentang recorded in Synopsis of Golden Chamber may be achieved by up-regulating TRPV1 expression to restore the level of autophagy mediated by AMPK.

Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.

ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis （AS） mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 （TRPA1）. MethodThe AS model was established on apolipoprotein E knockout （ApoE^-/-） mice with a high-fat diet. The mice were randomly divided into low-dose， middle-dose， and high-dose groups of Zhishi Xiebai Guizhitang （2.97， 5.94， 11.88 g·kg^-1） and simvastatin group （0.002 g·kg^-1）， and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process， the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin （HE） staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， and high density lipoprotein cholesterol （HDL-C） were detected， and the levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot and immunohistochemical method were used to analyze the expression of TRPA1， ATP-binding cassette transporter A1 （ABCA1）， ATP-binding cassette transporter G1 （ABCG1）， and mannose receptor （CD206）. ResultFrom the perspective of drug efficacy， compared with the normal group， pathological changes such as plaque， a large number of foam cells， and cholesterol crystals appeared in the aorta of the model group， and the serum levels of TC， LDL-C， IL-1β， and IL-18 were significantly increased （P<0.01）. The HDL-C level was significantly decreased （P<0.01）， and the CD206 level in aortic tissue was significantly decreased （P<0.01）. Compared with the model group， the lipid deposition in the aorta was alleviated in all drug administration groups. In addition， except for the high-dose group of Zhishi Xiebai Guizhitang， all drug administration groups could significantly decrease the levels of TC and LDL-C （P<0.01）. In terms of inflammation， except for the middle-dose group of Zhishi Xiebai Guizhitang， the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups （P<0.05）. Moreover， Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206， and the difference was significant in the middle-dose and high-dose groups （P<0.05）. From the perspective of mechanism， the expression levels of TRPA1， ABCA1， and ABCG1 in the aorta in the model group were lower than those in the normal group （P<0.05）. Compared with the model group， all drug administration groups significantly increased the expression of TRPA1 in the aorta （P<0.05）， and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant （P<0.05）， which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows： the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1， which promotes cholesterol outflow in foam cells， thereby regulating cholesterol metabolism， intervening in inflammation level to a certain extent， and finally treating AS.

Multicellular tumor spheroids (MCTS) can simulate the structure and metabolic characteristics of tumors in vivo, which is of great significance to study the metabolic phenotype of tumor cells and the mechanism of drug intervention. In this study, esophageal cancer MCTS were constructed, and MCTS frozen sections were prepared after treated with different formulations of paclitaxel (PTX) including common PTX injection, PTX liposome and albumin bound PTX. MCTS mass spectrometry imaging analysis method was established by using air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI). The visualization of the permeation and enrichment process of PTX in MCTs after PTX treatment was realized, and the spatially resolved metabolomics of PTX injection group was studied. The results showed that the permeation and enrichment behavior of PTX in MCTs model were related to the formulations. The changes of endogenous metabolites in MCTs of esophageal cancer after treated with PTX injection had temporal and spatial characteristics. The metabolic changes of MCTS during the initial 0-4 hours were dominated by the down-regulation of middle-high polarity metabolites and some lipids in the central region of MCTS, while the metabolic changes of MCTS during 8-72 hours were mainly up-regulated by lipid metabolites in the peripheral region of MCTS. The combination of in vivo tumor-associated MCTs model with label free, highly sensitive and high coverage mass spectrometry imaging technology provided a new method and strategy for the study of pharmacometabolomics.

Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine （First Batch）， with the effect of activating Yang， dissipating mass， moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain， or even chest pain radiating to the back， wheezing， coughing， shortness of breath， and Qi reversal from the hypochondrium. In modern traditional Chinese medicine， Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system， digestive system， respiratory system and other diseases， among which coronary heart disease， unstable angina pectoris， myocardial infarction， sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent， with the pharmacological effects of improving intravascular environment， myocardial ischemia， myocardial ischemia-reperfusion injury， and myocardial hypoxia， anti-inflammation， plaque stabilisation， etc.， and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels， mainly including thromboxane B₂ （TXB₂）， prostacyclin I₂（PGI₂） and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase （PI3K/Akt/eNOS） signaling pathways， and ATP-sensitive potassium channels. In addition， the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 （TRPA1） has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases， which is worth of further study.

Atherosclerosis is a chronic inflammatory disease caused by lipid accumulation and vascular endothelial dysfunction. The Toll-like receptor （TLR）/nuclear transcription factor-κB （NF-κB） pathway and the NOD-like receptor protein 3 （NLRP3） inflammasome pathway play a proinflammatory role， while the transient receptor potential vanilloid subtype 1 （TRPV1） and transient receptor potential ankyrin 1 （TRPA1） play a protective role in the occurrence of atherosclerosis. We reviewed the relevant studies published in the last 10 years. The results showed that activation of TRPV1/TRPA1 could activate endothelial-type nitric oxide synthase （eNOS） and inhibit the generation of reactive oxygen species （ROS） and cholesterol crystal （CC） to modulate the TLR/NF-κB and NLRP3 inflammasome pathways， thereby inhibiting TLR/NLRP3-mediated inflammatory response. A variety of compound prescriptions and active components of Chinese medicinal materials can activate TRPV1/TRPA1 or its downstream pathway to regulate the TLR/NLRP3 pathway in atherosclerosis. This paper introduces the mechanisms of compound prescriptions and active components of Chinese medicinal materials in regulating the TLR/NLRP3 pathway via TRPV1/TRPA1 in atherosclerosis. This review provides new ideas for the research on the interactions between Chinese medicines in the treatment of atherosclerosis and provides a new strategy for the clinical treatment of atherosclerosis with traditional Chinese medicine.

ObjectiveTo study the effect and mechanism of Linggui Zhugantang in treating chronic bronchitis （CB） induced by exposure to cigarette smoke combined with tracheal instillation of lipopolysaccharide （LPS）. MethodSixty SPF-grade SD rats were randomly divided into normal， model， dexamethasone （1 mg·kg^-1）， and high-， medium-， and low-dose （30.06， 15.03， 7.515 g·kg^-1， respectively） Linggui Zhugantang groups by the body weight stratification method， with 10 rats in each group. Each group was administrated with 200 μL LPS （1 g·L^-1） by tracheal instillation on days 1 and 14， respectively， while the normal group was administrated with an equal volume of normal saline. Except the normal group， the other groups were exposed to cigarette smoke on days 2-13 and 15-30 （10 cigarettes/time/30 min， twice/day） for the modeling of CB. The rats were administrated with corresponding drugs by gavage for 30 consecutive days from day 2 of modeling， and the mental status， behavior， and body weights of the rats were observed and measured. The wet/dry mass ratio （W/D） of the left lung was measured 30 days after modeling. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung and bronchial tissues. The bronchial mucus secretion and goblet cell proliferation were observed by Alcian blue-periodic acid Schiff （AB-PAS） staining. The levels of mucin 5AC （MUC5AC）， interleukin （IL）-13， IL-6， and tumor necrosis factor （TNF）-α in the serum were determined by enzyme-linked immunosorbent assay. The expression of phospholipase A2 （PLA2）， transient receptor potential vanilloid receptor 1 （TRPV1）， and transient receptor potential ankyrin 1 （TRPA1） in the lung tissue was quantitatively analyzed by immunohistochemistry and Western blot. ResultCompared with the normal group， the model group showcased abnormal mental status and behaviors， bloody secretion in the nose and mouth， the mortality rate of 40%， decreased body weight， severe lung bronchial structure damage， a large number of inflammatory mediators and inflammatory cell infiltration in the tube wall， hyperemia， edema， and fibroplasia， massive proliferation of goblet cells， excessive secretion and accumulation of mucus， stenosis and deformation of the lumen， and aggravation of pulmonary edema （P<0.01）. In addition， the model group had higher levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and higher expression of PLA2 in the lung tissue than the normal group （P<0.01）. Compared with the model group， the medication groups showed normal mental status and behaviors， reduced mortality rate， stable weight gain， reduced lung and bronchial injuries， decreased goblet cell proliferation and mucus secretion， and alleviated pulmonary edema （P<0.01）. Furthermore， Linggui Zhugantang lowered the levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and down-regulated the protein levels of PLA2， TRPV1， and TRPA1 in the lung tissue （P<0.01）. ConclusionLinggui Zhugantang can reduce the pulmonary inflammation and airway mucus hypersecretion in the rat model of chronic bronchitis. It may exert the effects of reducing inflammation and resolving phlegm by regulating the PLA2-TRPV1/TRPA1 pathway.