Animals ; Camptothecin ; pharmacology ; Liver Neoplasms, Experimental ; immunology ; Mice ; Neoplasm Transplantation ; Sarcoma, Experimental ; immunology ; Transplantation, Isogeneic

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

OBJECTIVETo reveal the transmembrane signal pathway participating in regulating neuron functions of treating Alzheimer's disease (AD) by acupuncture.

METHODSSAMP8 mice was used for AD animal model. The effect of acupuncture method for qi benefiting, blood regulating, health supporting, and root strengthening on the amount and varieties of transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice was detected using HPLC MS/MS proteomics method.

RESULTSCompared with the control group, acupuncture increased 39 transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice, of them, 14 belonged to ionophorous protein, 8 to G protein, 8 to transmembrane signal receptor, and 9 to kinase protein. Totally 3 main cell signal pathways were involved, including G-protein-coupled receptors signal, enzyme linked receptor signal, and ion-channel mediated signal. Compared with the sham-acupuncture group, acupuncture resulted in significant increase of kinase signal protein amount. From the aspect of functions, they were dominant in regulating synapse functions relevant to cytoskeleton and secreting neurotransmitters.

CONCLUSIONThe cell biological mechanism for treating AD by acupuncture might be achieved by improving synapse functions and promoting the secretion of neurotransmitters through transmembrane signal transduction, thus improving cognitive function of AD patients.

Acupuncture Therapy ; Alzheimer Disease ; metabolism ; Animals ; Disease Models, Animal ; Female ; Male ; Membrane Microdomains ; metabolism ; Mice ; Proteomics ; Signal Transduction ; Tandem Mass Spectrometry

Objective To detect the expression and content of decorin in fibroblasts of keloid to deeply reveal the mechenism and the role of decorin plays in scar formation.Methods Fibroblasts of keloid,normal scar and normal skin were cultured in vitro,and the morphology,activity,apoptosis of fibroblast were observed under light microscope and electron microscope; the mRNAs of decorin and TGF-β1 were detected and analyzed with real-time fluorescent quantitative-PCR (FQ-PCR).Results Fibroblasts of keloid showed irregular morphology,larger size and disorder arrangement.There were a large number of mitochondria,swelling rough endoplasmic reticulum,and euchromatin-rich in nucleus of fibroblasts,suggesting the protein synthesis of keloid fibroblast was very active.Compared with normal skin,the expression of decorin was significantly lower in keloid fibroblast; On the contrary,the expression of TGF-β1 was significantly higher in keloid fibroblast than in normal scar and normal skin.Conclusions Compared with normal skin,the expression of decorin in keloid fibroblast is significantly lower.Lower content of decorin in early stage of wound healing may induce weakly suppression of proliferation and synthesis of fibroblast,and up-regulate the activity of TGF-β1,which promotes the proliferation,migration and excessive collagen synthesis of the fibroblast of keloid.Thus,decorinis an suppressor factor of keloid formation.

Objective To study the conventional MRI and dittusion weighted imaging(DWI) features of Japanese encephalitis(JE)in children.Methods Sixteen patients with JE were included. Conventional MRI and DWI sequences were performed in all patients.Seven patients received MRI within 10 days of onset and 9 after 10 days.The appearances on DWI and T_2 WI were recorded.The ADC values of lesions were calculated,and then were correlated with the corresponding time interval between onset of neurological symptoms and MRI scanning.Results The lesions of JE mainly showed long T_1 and long T_2 signal intensity on MRI.The thalami were the most frequently involved areas,and 15 out of 16 showed thalamic involvement and 6 patients only showed thalamic abnormalities without other lesions.Seven patients within 10 days of onset showed lesions with high signal intensity on both DWI and T_2WI,but whole or partial lesions showed clearer on DWI than on T_2WI,and 2 patients showed extra lesions that were invisible on T_2WI.As for the other 9 patients after 10 days of onset,the lesions showed clearer on T_2WI than on DWI. There was a direct correlations between thalamic ADC values and the disease duration (r=0.84,P

OBJECTIVETo provide anatomic evidence for identification of "holy plane" between fascia propria and its adjacent fascia in total mesorectal excision.

METHODSA total of 26 pelvic specimens of adult male preserved in 10% formalin solution were used in this study. Twenty pelvis were employed for topographic anatomy, six for sectional anatomy.

RESULTSRectovesical septum was formed by the ventral part of the fascia propria and Denonvilliers' fascia, with no blood vessel and nerve coursed between two layers. Dorsal part of the fascia propria parallelled with the presacral fascia, with no blood vessel and nerve coursed between two layers in 80% of the pelvis. However, anatomic variations was encountered occasionally--with muscle-like tissue or fusion of presacral fascia interposed between them for 20%. The lateral space of rectum was between lateral part of the fascia propria and parietal fascia which witnessed pelvic nerve plexus and lateral ligament of the rectum traveling. Pelvic nerve plexus was categorized as two types according the relation between fascia propria and nerve plexus: fusion type accounting for 85% and rarefaction type for 15%.

CONCLUSION'holy plane' is sandwiched between the fascia propria and its adjacent fascia--ventrally Denonvilliers fascia, dorsally presacral fascia and laterally parietal fascia.

Adult ; Autopsy ; Fascia ; anatomy & histology ; Fasciotomy ; Humans ; Male ; Rectum ; anatomy & histology ; surgery

The present study aimed to explore whether the stretch of ischemic myocardium could modulate the electrophysiological characteristics via mechanoelectric feedback (MEF), as well as the effect of phalloidin on the electrophysiological changes. Thirty-two Wistar rats were randomly divided into 4 groups: control group (n=9), phalloidin group (n=7), myocardial infarction (MI) group (n=9), MI + phalloidin group (n=7). The acute myocardial infarction (AMI) was conducted by ligation of the left anterior descending (LAD) coronary artery for 30 min in isolated rat heart. The volume alternation of a water-filled latex balloon in the left ventricle produced the stretch of myocardium. After perfused on Langendorff, the isolated hearts were stretched for 5 s by an inflation of 0.1, 0.2 and 0.3 mL separately and the effect of stretch was observed for 30 s, including the left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dp/dt(max), monophasic action potential duration at 90% repolarization (MAPD90), and occurrence of premature ventricular beats (PVB) and ventricular tachycardia (VT). The stretch caused an increase of MAPD(90) in both control and MI rats (P<0.05, P<0.01). Moreover, MAPD(90) in MI group increased more significantly than that in the control group at the same degree of stretch (P<0.05, P<0.01). Phalloidin (1 μmol/L) had no effect on MAPD(90) in basal state. After stretch, MAPD(90) in phalloidin group slightly increased but was not significantly different from that in the control group. However, phalloidin reduced MAPD(90) in infarcted myocardium, especially when ΔV=0.3 mL (P<0.05). The incidence rates of PVB and VT in MI group were higher than that in the control group (both P<0.01). And there was no significant difference in the incidence rates of PVB and VT between phalloidin group and control group. Phalloidin inhibited the occurrence of PVB and VT in infarcted hearts (both P<0.01). LVSP and +dp/dt(max) in MI group obviously decreased (P<0.01 vs control). With application of phalloidin, LVSP slightly, but not significantly increased in infarcted hearts, while -dp/dt(max) significantly increased (P<0.05). It is suggested that MI facilitates the generation and maintenance of malignant arrhythmias, while phalloidin obviously inhibits the occurrence of arrhythmias.
Action Potentials ; Animals ; Arrhythmias, Cardiac ; prevention & control ; Coronary Vessels ; Heart ; drug effects ; physiopathology ; Heart Ventricles ; Myocardial Infarction ; physiopathology ; Phalloidine ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVE To investigate the neuroprotective effect and possible mechanisms of lute-olin-7-O-β-D-glucuronide (LGU) against focalcerebral ischemic injury. METHODS The focal cerebral ischemic injury model was established by middle cerebral artery occlusion (MCAO). Male Sprague Dawley rats were randomly divided into sham group,model group(MCAO),LGU group(0.24,0.72 and 2.16 mg·kg-1)and positive control group(Edaravone at 5 mg·kg-1).LGU was injected intravenously 30 min after MCAO.Neurological severity score,infarct volume and brain water content were detected 24 h after MCAO and the levels of Na+-K+ATPase,Ca2+ATPase,TNF-α and IL-1β were detected to explore the possible mechanisms.For the therapeutic time window test,LGU(0.72 mg·kg-1)was injected intrave-nously 0.5, 2, 4, 6, 8, 10 and 12 h respectively after MCAO. To evaluate motion behavior, LGU were injected intravenously 30 min after MCAO and once per day during detection period. The changes of motor coordination were detected by rotating rod method and grip strength analysis, and the changes of gaits were detected using DigiGait Imaging System. RESULTS LGU improved the neurological severity score, infarct volume ratio and brain water content. The therapeutic time window of LGU for cerebral infarction and brain edema was at least 6 h and for neurological dysfunction was 12 h.LGU also prolonged the latency on rotarod, increased the forelimb tension and improved 8 gait parameters, including stance duration,stride length,stance width,paw area,paw area variability,gait symmetry,ataxia coefficient and tau propulsion.Furthermore,LGU increased Na+-K+-ATPase and Ca2+-ATPase levels in the cortex and hippocampus in the ischemic side,reduced the levels of TNF-α and IL-1β in the serum. CONCLUSION LGU has a significant neuroprotective effect against cerebral ischemic injury via improving energy metabolism and reducing inflammation.

The analysis of poorly conductive samples using discharge plasma is a significant challenge in determining elemental content by atomic emission spectrometry.In this study,graphite as a conductive medium was combined with metal salts and silica to prepare soil sample pellets.A tungsten needle electrode was employed to generate point discharge microplasma with the sample,exciting atomic emission signals of analyte elements.By using Cu 324.7 nm as the analytical line,both the capability to excite atomic emission spectral lines and the impact of experimental conditions were investigated,resulting in accurate determination of trace copper in both standard and real samples.This method held promise for detecting other metals like manganese,iron,and zinc.This work offered methodology for non-conductive sample analysis via discharge plasma atomic emission spectrometry,showing potential for rapid on-site assessment of soil samples.

The acupuncture technique of tonifying qi, regulating blood and strengthening the primary source of human life is established on the base of the new pathology of dementia due to dysfunction of sanjiao by Prof. HAN Jing-xian. It is held that Tanzhong (CV 17), Zhongwan (CV 12), Qihai (CV 6), Xuehai (SP 10), Zusanli(ST 36) and Waiguan (TE 5) were the basic points for treatment of dementia. There are 3 characteristics of the point combination. Firstly, emphasis should be put on regulation of the stomach and the spleen so as to promote transportation, transformation and distribution; secondly, monarch, minister, assistant and guide points should be selected on the base of meridians, and more attention should be paid to the entity and connections among organs; and thirdly, treatment should be given according to physiological functions of the viscera.
Acupuncture Points ; Acupuncture Therapy ; methods ; Blood Circulation ; Humans ; Medicine, Chinese Traditional ; Qi