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From the perspective of β-amyloid (Aβ) toxicity and synaptic plasticity, the mechanism of electroacupuncture to improve learning and memory ability in the early pathological stages of Alzheimer's disease was explored.Twelve male amyloid-protein precursor (APP)/γ-secretase (PS1) double transgenic AD mice were randomly and equally divided into electroacupuncture (EA) group and model group, and other 6 male C57BL/6 mice were used as the normal group. EA (1 Hz/50 Hz, 0.5 mA) was applied to "Baihui" (GV20) and bilateral "Yongquan"(KI1) for 15 min, once every other day for 6 weeks. Immunofluorescence was used to observe the positive expression of Aβ in the left hippocampus. Immunohistochemistry was used to observe the positive expression of postsynaptic density-95 (PSD-95) in the left hippocampus. Western blot was used to detect the expression of PSD-95 and synaptophysin (SYN)in the right hippocampus.Immunofluorescence results showed that extracellular Aβ was seen in the model group and electroacupuncture group, but no senile plaques were seen. Compared with the normal group, the expression level of Aβ in the hippocampus of the model group increased significantly (EA can reduce the expression of Aβ in the hippocampus of APP/PS1 mice and increase the expression of PSD-95 and SYN, which may contribute to its effect in improving the synaptic plasticity.

A subchronic toxicity study were conducted in Wistar Han RCC rats to evaluate the potential health effects of genetically modified (GM), drought-tolerant wheat MGX11-10. Rats were fed a rodent diet formulated with MGX11-10 and were compared with rats fed a diet formulated with its corresponding non-transgenic control Jimai22 and rats fed a basal diet. MGX11-10 and Jimai22 were ground into flour and formulated into diets at concentrations of 16.25, 32.5, or 65%, w/w% and fed to rats (10/sex/group) for 13 weeks. Compared with rats fed Jimai22 and the basal-diet group, no biologically relevant differences were observed in rats fed the GM diet with respect to body weight/gain, food consumption/efficiency, clinical signs, mortality, ophthalmology, clinical pathology (hematology, prothrombin time, urinalysis, clinical chemistry), organ weights, and gross and microscopic pathology. Under the conditions of this study, the MGX11-10 diets did not cause any treatment-related effects in rats following at least 90 days of dietary administration as compared with rats fed diets with the corresponding non-transgenic control diet and the basal-diet group. The MGX11-10 diets are considered equivalent to the diets prepared from conventional comparators. The results demonstrated that MGX11-10 wheat is as safe and wholesome as the corresponding non-transgenic control wheat.

Lower heart rate variability (HRV) is known to make patients more susceptible to tachycardia and possibly sudden unexpected death in epilepsy (SUDEP). The heart rate (HR) at which tachycardia is present may vary by age. To date, no study has been done comparing adult and child seizures at different time points. The purpose of this study was to compare the frequency of HR changes with ictal tachycardia (IT) seizures at different time points in adults versus children. We retrospectively assessed the changes in the HR of 99 IT seizures in children and 96 IT seizures in adults. The difference between adults and children in gender, hemispheric lateralization or sleep/wakefulness, or seizure type on the HR changes and the difference between children and adults during 10 s preictal, ictal onset, and ictal and 60 s postictal were separately assessed. The HR difference and maximum HR increase with aging in children. The seizure duration in adults lasted longer as compared with that in children. There are higher HR at different points and HR difference at 10 s preictal as compared to baseline in children. The study illustrates that age and duration were respectively related to HR differences distinguishing children from adults. There may be an age-related effect of HR changes associated with seizures, with higher HR at different times and HR difference at 10 s before seizure onset as compared to baseline in children, which might explain that children are more likely to predict epileptic seizures than adults, contributing to subclinical seizures and treatment efficiency in refractory patients.

Migraine is a disabling neurovascular disorder, which increases risk of cardiovascular events and is a social burden worldwide. The present first-line anti-migraine medications can cause overwhelming side-effects, of which one includes the onset of cardiovascular disease. As one of the marketed Tibetan drugs, Ru-yi-Zhen-bao Pills (RYZBP) have been clinically used to treat cardiovascular disorders and as anti-migraine medication. However, there is currently no research exploring the anti-migraine actions of RYZBP.The current research was designed to assess the anti-migraine roles of RYZBP and explore the underlying mechanisms in a nitroglycerin (NTG)-induced migraine rat model trial.120 rats were randomly divided into the following six groups of 20 rats each: normal control group, model control group, positive control group, and RYZBP high/medium/low-dose groups (Ru-yi-Zhen-bao Pills; TH 1.00 g/kg, TM 0.50 g/kg and TL 0.25 g/kg). All rats were administered intragastrically for 7 consecutive days, which were subcutaneously injected with the NTG (10 mg/kg) after the last gavage (except in the normal control group). 3min after NTG treatment, 30 rats (5 rats from each group) were anesthetized and devoted to electroencephalogram(EEG) testing, which was used to evaluate the analgesic effect of RYZBP. One hour after NTG treatment, the rest of the 90 rats (15 rats from each group) were anesthetized and midbrain tissue sample was dissected. The dissection was then washed with physiological saline and collected. The histopathological changes in the periaqueductal gray(PAG) of 5 tissue samples were determined by aematoxylin-eosin (HE) staining, as well as an estimation of substance P (SP) and neurokinin 1 receptor (NK1R) expression through immunohistochemically staining(IHC). Another 5 midbrain preparations were carried out to evaluate calcitonin gene-related peptide (CGRP), proenkephalin (PENK), SP, and cholecystokinin (CCK) expressions by real-time quantitative polymerase chain reaction (RT-qPCR). The rest of the 5 brainstem tissues were then used to measure CCK, CGRP, and opioid peptide receptor (DORR) levels by western blotting(WB).In the EEG test, RYZBP (TM 0.50 g / kg) treatment transformed the EEG pain-wave of the NTG-induced migraine model rats in different time period. In the mechanism assay, compared with the model control group, RYZBP pretreatment reduced inflammatory cell infiltration, fibrosis and vacuolation of neuronal cells of PAG tissue seen by HE staining. IHC experiments further showed that RYZBPTM up-regulated SP expression levels and enhanced NK1R levels in the NTG-induced migraine rats (P 0.05). Therapeutic administration of RYZBP also increased PENK mRNA expression and DORR protein level. Both RT-qPCR and western blotting trials indicated that RYZBP treatment significantly decreased CCK and CGRP expression levels (P 0.01 or P 0.05) in the NTG-induced migraine rats.RYZBP has the potential to be an effective anti-migraine treatment through suppressing the EEG pain-wave, increasing the levels of SP, PENK, DORR and reducing expression of CCK and CGRP. Mediating the PAG anti-nociceptive channel and inhibiting central sensitization were the two potential mechanisms, which offers further evidence for clinical therapy.

A 90-day feeding study in rats was conducted to evaluate the subchronic oral toxicity of genetically modified (GM) DAS-81419-2 soybean. Wistar rats were fed with diets containing toasted soybean meal produced from DAS-81419-2 soybean grain that expresses the Cry1F, Cry1Ac, and Pat proteins or containing conventional soybean at doses of 30.0%, 15.0%, 7.5%, or 0% (control group) for 90 consecutive days. The general behavior, body weight and food consumption were observed. At the middle and end of the experiment, blood, serum, and urine samples were collected for biochemical assays. At the conclusion of the study, the internal organs were weighed and histopathological examination was completed. The rats exhibited free movement and shiny coats without any abnormal symptoms or abnormal secretions in their noses, eyes, or mouths. There were no adverse effects on body weight in GM soybean groups and conventional soybean groups. No biological differences in hematological, biochemical, or urine indices were observed. No significant differences in relative organ weights were detected between the experimental groups and the control group. No histopathological changes were observed. Under the conditions of this study, DAS-81419-2 soybean did not cause any treatment-related effects in Wistar rats following 90 days of dietary administration.

BACKGROUND/AIMS To evaluate the diagnostic significance of appendiceal orifice inflammation (AOI) in ulcerative colitis (UC) patients. MATERIALS AND METHODS We retrospectively examined data from patients with colitis from May 2010 to January 2014 and assigned them to two groups: UC cases and specific colitis cases. First, we clarified the difference in the AOI+ rate between the two groups. Thereafter, imaging findings of all the patients with colitis were re-examined. Features of AOI alone or in combination with proctitis (referred to as "combination features") were considered as the two separate diagnostic criteria for diagnosing UC. By comparing the current diagnoses with the previous diagnoses, evaluation indexes were obtained. RESULTS A total of 3582 colitis cases (UC cases: 427; specific colitis cases: 3155) were examined. The mean AOI+ rates in UC and specific colitis cases were 26.2% and 0.7%, respectively; a Chi-squared test indicated that the difference between these rates was statistically significant (x2=6.81; p

This study aimed to investigate the effects of baldrinal of Valeriana jatamansi on the expression of corticotropin releasing factor (CRF) and tryptophan hydroxylase 1 (TPH1) mRNA and levels of 5-hydroxytryptamine (5-HT) in colon of rats with irritable bowel syndrome (IBS), and to explain its therapeutic mechanism on IBS through 5-HT pathway. Fifty-four male SD rats were randomly divided into 6 groups: blank group, model group, baldrinal high, medium and low dose groups, and pinaverium bromide group, n=9 in each group. The IBS rat models were established by using unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest and independent feeding. CRF expression was detected by IHC-P; TPH1 mRNA expression was detected by using RT-PCR and the 5-HT level was measured by high performance liquid chromatography(HPLC). The results indicated that the method of chronic stress with acute restrain stress method and independent feeding could lead to the increase in expressions of CRF and TPH1 mRNA and levels of 5-HT in IBS rats(P0.05). The expressions of CRF, TPH1 mRNA and 5-HT in baldrinal groups were significantly lower than those in model group(P0.05). The experimental results showed that IBS could result in increase in the expressions of CRF, TPH1 mRNA and levels of 5-HT, and the baldrinal of V. jatamansi could improve the symptoms of IBS by reducing the expressions of CRF, TPH1 mRNA and levels of 5-HT in colon of rats.

Ten glioma cell lines were examined for abnormalities of exon 1beta of the p14 gene and then for abnormalities of the entire p14 gene with the use of previous findings of other exons. Abnormalities of exon 1beta and the entire p14 gene were detected in eight of ten cases: homozygous deletion of the entire gene in six cases, hemizygous deletion of exon 1beta with homozygous deletion of downstream exons in one case, and hemizygous deletion of the entire coding region with a missense mutation (A97V) at the C-terminal nucleolar localization domain in one case. The remaining two cases revealed no such abnormalities. p14 gene expression was observed in the latter two cases and one case with A97V mutation in the hemizygously deleted coding region, but not in the others, including one case with only exon 1beta. In the three cases with p14 gene expression, immunocytochemistry revealed p14 nucleolar staining, suggesting the retention of the functional activity of p14 protein and, in the case with the A97V mutation, an insufficient mutational effect as well. The present findings of the frequent and variable p14 gene abnormalities, including rare-type ones with or without sufficient mutational effect in glioma cell lines, might be of value for better understanding of the p14 gene and its related pathways in glioma carcinogenesis.

Tocotrienols have been shown many biologic functions such as antioxidant, anti-cancer, maintaining fertility and regulating the immune system and so on. In this study, after feeding with tocotrienol-rich fraction from palm oil (TRF) for 2 weeks, Balb/c nude mice were inoculated human colon SW620 cancer cell and then continued to feed TRF for 4 weeks. At termination of experiments, xenografts were removed and determined the expression of Wnt-pathways related protein by immunohistochemistry or western blotting. Liver tissues were homogenated for determining the levels of antioxidative enzymes activity or malondialdehyde (MDA). The results showed that TRF significantly inhibited the growth of xenografts in nude mice. TRF also affected the activity of antioxidative enzymes in the liver tissue of mice. These changes were partly contributed to activation of wnt pathways or affecting their related protein. Thus, these finding suggested that the potent anticancer effect of TRF is associated with the regulation of Wnt signal pathways.

Using reverse transcription-polymerase chain reaction (RT-PCR), six primary brain lymphomas, pathologically diagnosed as diffuse large B-cell lymphoma, were examined for rearranged V H -D-J H sequences of the immunoglobulin heavy chain gene, focusing on somatic mutations and intraclonal heterogeneity. The reliability of the isolated PCR clones was confirmed by in situ hybridization (ISH) with complementarity-determining region (CDR) 3 oligonucleotide probes. Sequence analysis of the PCR clones revealed a high frequency of somatic mutation, ranging from 8.8 to 27.3% (mean 18.2%) in the V H gene segments in all the lymphomas. A significantly lower frequency of replacement (R) mutations than expected was also seen in their frameworks (FRs) in all cases. These findings suggested that the precursor cells were germinal center (GC)-related cells in these lymphomas. However, despite extensive cloning experiments, intraclonal heterogeneity was not detected in any case except for one in which it could not be ruled out. Thus, it seemed likely that all of our brain lymphomas were derived from GC-related cells and that at least most of them were from post-GC cells.

AIM: To evaluate the effect of suspended moxibustion (SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity (CVH) in rats. METHODS: SM was administered once daily to 37-d-old CVH rats for 7 d. The two pairs of acupoints (ST25 and ST37, bilateral) were simultaneously treated with SM. Each treatment lasted for 30 min. Rats undergoing treatment with SM were not anesthetized. Untreated CVH rats and normal rats were used as controls. The abdominal withdrawal reflex was determined 30-90 min after the seven treatments. The hypothalamic corticotropin-releasing hormone (CRH) mRNA level was measured using real-time quantitative reverse transcription-polymerase chain reaction. RESULTS: We found that SM treatment significantly decreased visceral sensitivity to colorectal distention in this rat model. In treated animals, SM also decreased the relative hypothalamic CRH mRNA expression level to control levels. CONCLUSION: Lower hypothalamic CRH levels may mediate the beneficial effects of SM in this rat irritable bowel syndrome model.

The objective of this study was to evaluate the effect of pulsatile flow on cerebral blood flow (CBF) in infants with the use of a mild hypothermic cardiopulmonary bypass (CPB). Thirty infants scheduled for open heart surgery were randomized to the pulsatile group (Group P, n = 15) and nonpulsatile group (Group NP, n = 15). In Group P, pulsatile perfusion was applied during the aortic cross-clamping period, whereas nonpulsatile perfusion was used in Group NP. The systolic peak velocity (Vs), the end of diastolic velocity (Vd), the mean velocity (Vm), and the pulsatility index (PI) and the resistance index (RI) of the middle cerebral artery were measured by a transcranial Doppler (TCD) ultrasound after anesthesia (T1; baseline), at the beginning of CPB (T2), 10 min after aortic cross-clamping (T3), 3 min after declamping (T4), at the cessation of CPB (T5), and at the end of the operation (T6). During T3 and T4, the Vs in Group P was significantly higher than in Group NP. However, there were no statistically significant differences between Vd and Vm. The PI and RI in Group P were also higher than those in Group NP (both P 0.05). During T5, Vd and Vm were higher in Group P (P 0.05), whereas there was no difference in Vs. Additionally, PI and RI in Group P were significantly lower than those in Group NP (P 0.05). However, there was no difference during T6. Pulsatile perfusion may increase CBF and decrease cerebral vascular resistance in the early period after mild hypothermic CPB.

Anatomical studies have shown that the globus pallidus receives abundant 5-hydroxytryptamine (5-HT) innervations from raphe nuclei. 5-HT may occupy an important position in the modulation of motor function through its affect on the activity of globus pallidus. In the present study, intrapallidal microinjection of 5-HT (0.1 mM) alone did not induce any motor behavior or postural asymmetry in the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. However, when infused concomitantly with a low dose of 3, 4-dihydroxyphenylalanine (L-DOPA, 3 mg/kg i.p.), which itself can induce modest contralateral rotational behavior, 5-HT significantly potentiated the number of contralateral rotations. To elucidate the cellular mechanism, in vivo extracellular recordings were performed to examine the effects of 5-HT on globus pallidus neurons. In normal rats, the predominant effect of micropressure ejection of 5-HT on pallidal neurons was excitation. In 6-OHDA-lesioned rats, although 5-HT increased the firing rate in most pallidal neurons, 5-HT-induced inhibitory effects was stronger than that on the unlesioned side as well as normal rats. Furthermore, 5-HT1B receptors are mainly involved in 5-HT-induced excitation while 5-HT1A receptors are involved in 5-HT-induced inhibition. The results suggest that 5-HT may potentiate the antiparkinsonian effect of L-DOPA through modulating the activity of globus pallidus. © 2009 Wiley-Liss, Inc.

Ten primary central nervous system lymphomas (PCNSL, brain lymphomas) were examined for p14 gene exon 1β deletion, mutation and methylation by Southern blot analysis, nucleotide analysis of polymerase chain reaction clones and Southern blot-based methylation assay. In Southern blot analysis, from the signal densities of the hybridized bands and their similarities to those of exons 2 and 3 in our previous quantitative study, we found that exon 1β was homozygously deleted in four cases, hemizygously deleted in five cases and not deleted in one case. Thus, the same deletion patterns covered the entire p14 gene for all cases except for one case, which suggested the hemizygous deletion of exons 1β and 2 and homozygous deletion of exon 3. In addition, although exon 1β mutation is rare in various tumors, we detected a missense mutation (L50R) in one case with a hemizygous deletion. Methylation of the 5′CpG island of the p14 gene was not suggested for any case without homozygous deletion. Our observation of frequent p14 gene abnormalities (90%) and inactivation (40–60%) was in striking contrast to the same pathological subtype of systemic lymphoma in which p14 gene abnormalities and inactivation were infrequent, suggesting a difference in carcinogenesis between PCNSL and systemic lymphoma. (Cancer Sci 2005; 96: 38 –41)

To observe the expression and distribution changes of connexin 43 (CX) in rats' myocardium after simulated microgravity and explore the partial mechanism of arrhythmia.Male Wistar rats were randomly assigned to either tail-suspension group (SUS) or control group (CON). Immunohistochemistry and Western Blot were used to detect the expression and the distribution of CX43. Electromicroscope was used to observe the ultrastructural changes.In SUS group, the decrease of CX43 and the distribution disturbance were obvious (P0.05), the proportion of the side-to-side gap junction increased (P0.05), and space between some gap junctions disappeared.The results show that CX43 decreased significantly and distributed irregularly after simulated microgravity. These can cause the changes of cardiac electric conduction velocity and direction. As a result, conduction block and reentry may occur. And these might be the partial mechanism of cardiac arrhythmia.