Ablation of Lrp4 in Schwann Cells Promotes Peripheral Nerve Regeneration in Mice.

Low-density lipoprotein receptor-related protein 4 (Lrp4) is a critical protein involved in the Agrin-Lrp4-MuSK signaling pathway that drives the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). Many studies have shown that Lrp4 also functions in kidney development, bone formation, nervous system development, etc. However, whether Lrp4 participates in nerve regeneration in mammals remains unknown. Herein, we show that Lrp4 is expressed in SCs and that conditional knockout (cKO) of Lrp4 in SCs promotes peripheral nerve regeneration. In Lrp4 cKO mice, the demyelination of SCs was accelerated, and the proliferation of SCs was increased in the injured nerve. Furthermore, we identified that two myelination-related genes, Krox-20 and Mpz, were downregulated more dramatically in the cKO group than in the control group. Our results elucidate a novel role of Lrp4 in peripheral nerve regeneration and thereby provide a potential therapeutic target for peripheral nerve recovery.

[Analysis of Regularity of Acupoint Selection in Acupuncture Treatment of Urticaria Based on Data Mining Technology].

OBJECTIVE: To analyze the regularity of acupoint selection, main acupoints and theoretical basis in acupuncture treatment of urticaria. METHODS: Papers collected from the time of establishment of each database to September of 2017 were retrieved from databases CNKI, CBM, VIP and WF by using keywords of "acupuncture" "moxibustion" "blood-letting therapy" "autohemotherapy" "cupping" "acupoint catgut embedding" "auricular points" "acupoint injection" "fire-needle" (or red-hot needle), "dermal needle" "needle-embedding" "urticaria" in both Chinese and English. The collected papers were brought into analysis according to the inclusion and exclusion criteria, from which the prescriptions for acupuncture treatment of urticaria were subjected into descriptive statistical analysis, association rule analysis, and cluster analysis by using Access 2010, Clementine 18.0 and Stata software. RESULTS: Outcomes of analysis indicated that the treatment methods of urticaria with acupuncture and moxibustion, with different emphases, may be classified into eight categories. For treating the exterior syndrome of urticaria, acupoints of the Bladder Meridian, Governor Vessel and Conception Vessel were often employed to harmonize Ying and Wei and to dispel the pathogenic wind, while for treating the interior syndrome, acupoints of the Large Intestine Meridian, Spleen Meridian, and Stomach Meridian were usually used to invigorate the spleen to dispel dampness and to regulate blood circulation. The top five frequently used acupoints were Quchi (LI 11), Xuehai (SP 10), Zusanli (ST 36), Sanyinjiao (SP 6) and Geshu (BL 17). It was crucial to make use of the specific acupoints with adequate meridian-qi, such as He-Sea points, Back-Shu points, and Yuan-Primary points. There were some fixed forms in the combination of acupoints, including LI 11, SP 10, Dazhui (GV 14) and auricular Lung, Shenmen, Fengxi, Adrenal gland, which had the highest confidence coefficient for the meridian points and ear acu-points, respectively. The outcomes of cluster analysis about the acupoint prescriptions showed that 12 acupoint groups as the SP 6-Hegu (LI 4)-LI 11-SP 10-ST 36, etc. were frequently used. CONCLUSION: The regularity of acupuncture treatment of urticaria can be discovered using data mining technology, resulting in an in-depth understanding and having a solid theoretical basis.

Long-term acupuncture treatment has a multi-targeting regulation on multiple brain regions in rats with Alzheimer's disease: a positron emission tomography study.

The acute effect of acupuncture on Alzheimer's disease, i.e., on brain activation during treatment, has been reported. However, the effect of long-term acupuncture on brain activation in Alzheimer's disease is unclear. Therefore, in this study, we performed long-term needling at Zusanli (ST36) or a sham point (1.5 mm lateral to ST36) in a rat Alzheimer's disease model, for 30 minutes, once per day, for 30 days. The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning. Positron emission tomography images were processed with SPM2. The brain areas activated after needling at ST36 included the left hippocampus, the left orbital cortex, the left infralimbic cortex, the left olfactory cortex, the left cerebellum and the left pons. In the sham-point group, the activated regions were similar to those in the ST36 group. However, the ST36 group showed greater activation in the cerebellum and pons than the sham-point group. These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer's disease.

MicroRNA Profiling Response to Acupuncture Therapy in Spontaneously Hypertensive Rats.

MicroRNAs (miRNAs) are a group of endogenous noncoding RNAs that play important roles in many biological processes. This study aimed to check if miRNAs were involved in the response to acupuncture in rats. Microarray analysis was performed to compare the miRNA expression profiles of medulla in spontaneously hypertensive rats (SHRs) treated with or without acupuncture. Our microarray analysis identified 222 differentially expressed miRNAs in the medulla of SHRs treated with acupuncture at taichong acupoint. Among these miRNAs, 23 miRNAs with a significant difference were found in acupuncture-treated SHRs compared to untreated rats. These 23 miRNAs could regulate 2963 target genes which were enriched in at least 14 pathways based on our bioinformatic analysis. miRNA-339, miR-223, and miR-145 were downregulated in the medulla of SHRs compared to normotensive rats. Notably, these miRNAs were upregulated to basal levels in the medulla of SHRs treated with acupuncture at taichong in comparison with SHRs receiving acupuncture at nonacupoint group or SHRs without any treatment. Our findings have revealed significant changes of a panel of selective miRNAs in hypertensive rats treated at taichong acupoint. These data provide insights into how acupuncture elicits beneficial effects on hypertension.

Acupuncture may exert its therapeutic effect through microRNA-339/Sirt2/NFκB/FOXO1 axis.

Recently, we have found that a number of microRNAs (miRNAs) and proteins are involved in the response to acupuncture therapy in hypertensive rats. Our bioinformatics study suggests an association between these miRNAs and proteins, which include miR-339 and sirtuin 2 (Sirt2). In this paper, we aimed to investigate whether Sirt2 was a direct target of miR-339 in neurons. In human SH-SY5Y cells, the luciferase assay implied that Sirt2 was likely a target of miRNA-339. Overexpression of miR-339 downregulated Sirt2 expression, while knockdown of miR-339 upregulated Sirt2 expression in human SH-SY5Y cells and rat PC12 cells. In addition, overexpression of miR-399 increased the acetylation of nuclear factor-κB (NF-κB) and forkhead box protein O1 (FOXO1) in SH-SY5Y cells, which are known targets of Sirt2. Our findings demonstrate that miR-339 regulates Sirt2 in human and rat neurons. Since Sirt2 plays a critical role in multiple important cellular functions, our data imply that acupuncture may act through epigenetic changes and subsequent action on their targets, such as miRNA-339/Sirt2/NF-κB/FOXO1 axis. Some physiological level changes of neurons after altering the miR-339 levels are needed to validate the suggested therapeutic role of miR-339/Sirt2/NF-κB/FOXO1 axis in response to acupuncture therapy in the future work.

Acupuncture for ischemic stroke: cerebellar activation may be a central mechanism following Deqi.

The needling sensation of Deqi during acupuncture is a key factor of influencing acupuncture outcome. Recent studies have mainly focused on the brain function effects of Deqi in a physiological state. Functional magnetic resonance imaging (fMRI) on the effects of acupuncture at Waiguan (SJ5) in pathological and physiological states is controversial. In this study, 12 patients with ischemic stroke received acupuncture at Waiguan (SJ5) and simultaneously underwent fMRI scanning of the brain, with imaging data of the activated areas obtained. Based on the patient's sensation, imaging data were allocated to either the Deqi group or non-Deqi group. In the Deqi group, the activated/deactivated areas were the left superior temporal gyrus (BA39)/right anterior lobe of the cerebellum and left thalamus. In the non-Deqi group, the activated areas included the medial frontal gyrus of the right frontal lobe (BA11), right limbic lobe (BA30, 35), and left frontal lobe (BA47), while the only deactivated area was the right parietal lobe (BA40). Compared with the non-Deqi group, the Deqi group exhibited marked activation of the right anterior lobe of the cerebellum and right limbic lobe (BA30). These findings confirm that the clinical effect of Deqi during acupuncture is based on brain functional changes. Cerebellar activation may be one of the central mechanisms of acupuncture in the treatment of ischemic stroke.

Adenosine as a probing tool for the mechanistic study of acupuncture treatment.

To date, acupuncture has been widely used despite a lack of solid clinical evidence in the East and West. However, there are few validated in vitro models for the mechanistic studies of acupuncture. We hypothesized that adenosine could be used as a probing tool in the mechanistic studies of acupuncture because of its critical role in the action of acupuncture. Subsequently, we tested this hypothesis using both in vitro and in vivo experiments. First, we found that adenosine stimulation mimicked the effect of acupuncture on microRNA profiling (including miR-339, miR-145 and miR-451) and protein level (including Sirt2) in nerve growth factor-induced differentiated PC12 cells. These miRNA and proteins have been found to be regulated by acupuncture treatment in the brain of spontaneously hypertensive rats. Next, we found that adenosine stimulation downregulated miR-339 expression through adenosine A1 receptor-mediated pathway. Finally, we showed that the concentration of adenosine was actually decreased in the brain of spontaneously hypertensive rats after acupuncture treatment at Taichong acupoint. Taken together, these findings suggest that adenosine could be used as a useful probing tool for acupuncture mechanistic studies, while more validation studies are certainly warranted.

Transcription factor ZBED6 mediates IGF2 gene expression by regulating promoter activity and DNA methylation in myoblasts.

Zinc finger, BED-type containing 6 (ZBED6) is an important transcription factor in placental mammals, affecting development, cell proliferation and growth. In this study, we found that the expression of the ZBED6 and IGF2 were upregulated during C2C12 differentiation. The IGF2 expression levels were negatively associated with the methylation status in beef cattle (P < 0.05). A luciferase assay for the IGF2 intron 3 and P3 promoter showed that the mutant-type 439 A-SNP-pGL3 in driving reporter gene transcription is significantly higher than that of the wild-type 439 G-SNP-pGL3 construct (P < 0.05). An over-expression assay revealed that ZBED6 regulate IGF2 expression and promote myoblast differentiation. Furthermore, knockdown of ZBED6 led to IGF2 expression change in vitro. Taken together, these results suggest that ZBED6 inhibits IGF2 activity and expression via a G to A transition disrupts the interaction. Thus, we propose that ZBED6 plays a critical role in myogenic differentiation.

[Efficacy on perennial allergic rhinitis treated with acupuncture at three nasal poinits and the acupoints selected by syndrome differentiation].

OBJECTIVE: To compare the difference in the clinical efficacy on perennial allergic rhinitis between three nasal points acupuncture therapy and the oral administration of loratadine so as to provide the better acupuncture program in clinical treatment. METHODS: Sixty cases were randomized into an acupuncture group (30 cases) and a medication group (30 cases). In the acupuncture group, acupuncture was applied to three nasal points [Yingxiang (LI 20), Yintang (EX-HN 3), Bitong (Extra)] and acupoints selected by syndrome differentiation. Acupuncture was given once every two days, three times a week, for 4 weeks totally. In the medication group, loratadine was prescribed for oral administration, 10 mg every day, for 4 weeks. The symptom and physical sign scores before and after treatment, as well the short-term and long-term efficacy were compared between the two groups. RESULTS: The total effective rate was 96.7% (29/30) in the acupuncture group and was 93.3% (28/30) in the medication group after treatment. The efficacy was similar between the two groups (P>0.05). In follow-up, the total effective rate was 86.7% (26/30) in the acupuncture group, which was better than 56.7% (17/30, P<0.05) in the medication group. The scores of symptoms and physical signs after treatment and in follow-up were all reduced apparently as compared with those before treatment in the patients of the two groups (all P<0.05). The scores of symptoms and physical signs were reduced more apparently in the acupuncture group as compared with those in the medication group in follow-up (all P<0.05). CONCLUSION: The acupuncture at three nasal points and the acupoints selected by syndrome differentiation achieves the similar short-term efficacy on perennial allergic rhinitis as compared with the oral administration of loratadine. The acupuncture therapy presents the obvious advantages on long-term efficacy.

Lateralisation of cerebral response to active acupuncture in patients with unilateral ischaemic stroke: an fMRI study.

OBJECTIVE: Acupuncture is beneficial in treating stroke neuropsychiatric symptoms. The present study aimed to identify functional brain response to active acupuncture in patients with unilateral ischaemic stroke using functional MRI (fMRI). METHODS: A total of 10 patients aged 47-65 years with left hemispheric ischaemic stroke received single-session manual acupuncture at the TE5 point of the affected (right) forearm. A 6-min tactile control procedure in which an acupuncture needle tip was alternately touched and removed from the skin at the acupuncture point for 30 s each was performed first, followed by active acupuncture in a blocking paradigm consisting of six 30-s twist blocks of rotation interspersed between six 30-s blocks of rest. A whole brain scan was simultaneously conducted on a 3.0-T imager. Activated and deactivated brain regions during tactile stimulation and active acupuncture relative to rest were obtained via group analysis. RESULTS: Compared to tactile stimulation, needling with twist manipulation modulated many more widespread brain areas. All the brain areas activated and deactivated by active acupuncture relative to tactile stimulation were distributed in the primary sensorimotor and medial frontal cortex of the unaffected, but not the affected hemisphere. CONCLUSIONS: Active acupuncture results in lateralisation of functional cerebral response to the contralateral unaffected hemisphere in patients with unilateral stroke. This lateralisation may represent an effect of acupuncture in enhancing a compensatory process by redistributing functions into the intact cortex, particularly in the unaffected hemisphere.

[Effect of needling at waiguan (SJ5) on brain glucose metabolism in patients with cerebral infarction].

OBJECTIVE: To observe changes of brain glucose metabolism by needling at Waiguan (SJ5) in cerebral infraction (CI) patients using 18F-fluorodeoxyglucose (FDG) positron-emission computer tomography (PET/CT), thus exploring its effect and mechanisms. METHODS: A total of 21 patients with CI were recruited in this study. The location of lesion was limited to the left basal ganglia by CT or MRI scan. All patients were randomly assigned to three groups. i.e., the acupoint group (Group A), the non-acupoint group (Group B), the blank control group (Group C), 7 in each group. Patients in Group A were needled at right Waiguan (SJ5). Those in Group B were needled at non-acupoint [10 mm beside Waiguan (SJ5)], whereas those in Group C did not receive any treatment. All patients underwent PET/CT head scan. All data were statistically analyzed using SPSS 13.0 Software and SPM8 Software. RESULTS: Compared with Group C, glucose metabolism increased in bilateral superior temporal gyrus (BA38), right superior frontal gyrus (BA9), left cingulate gyrus (BA24), left culmen and pyramid of cerebellum, and right cerebellar tonsil of cerebellum in Group A. Compared with Group C, glucose metabolism increased in bilateral superior frontal gyrus (BA6, BA9, BA10), bilateral middle frontal gyrus (BA6, BA10), left middle frontal gyrus (BA4), bilateral uncus of limbic lobe (BA36, BA38), left cingulate gyrus (BA24, BA31), left posterior cingulate gyrus (BA30), left precuneus (BA7), left inferior parietal lobule (BA4), and left lingual gyrus of occipital lobe (BA18) in Group B. Compared with Group B, glucose metabolism increased in bilateral superior temporal gyrus (BA22, BA38), right inferior frontal gyrus (BA47), left culmen and cerebellar tonsil of cerebellum in Group A. Activated encephalic regions of needling at Waiguan (SJ5) were mainly dominated in the healthy side, bilateral superior temporal gyrus, and right inferior frontal gyrus. Activated encephalic regions of cerebellum were located at the left cerebellar hemisphere, left culmen of anterior cerebella lobe, and bilateral cerebellar tonsil of posterior cerebella lobe. CONCLUSIONS: Needling at Waiguan (SJ5) of CI patients induced increased glucose metabolism in local cerebral regions. Functional neuroimaging using PET/CT could directly reflect changes of brain glucose metabolism by acupuncture.

[Evaluation of the immediate effect of acupuncture on cervical spondylosis of vertebral artery type based on orthogonal design].

OBJECTIVE: To analyze the differences in the immediate effect of acupuncture on cervical spondylosis of vertebral artery type among three factors: needling technique, acupoint selection and time of needle retaining so as to option the best therapeutic program. METHODS: Thirty-two cases were observed and randomly divided into 8 groups, 4 cases in each one. The orthogonal design of three factors and two levels was adopted. There were needling technique (electroacupuncture, reinforcing and reducing method), acupoint selection [C4-C7 Jiaji (EX-B 2) and three needles of neck: Tianzhu (BL 10), Jingbailao (EX-LHN 15), Dazhu (BL 11)] and time of needle retaining (5 min, 15 min). L8 (2(7)) orthogonal design table was arranged in the trial. The changes in mean velocity (Vm) of vertebral artery (VA) and basilar artery (BA) were observed before and after acupuncture. RESULTS: The immediate effect of VA-BA blood flow was the most significant after electroacupuncture at C4-C7 Jiaji (EX-B 2), with continuous wave for 5 min. This method and acupoint selection greatly influenced the therapeutic results (both P<0.05). CONCLUSION: The optimized therapeutic program of the immediate effect of acupuncture for cervical spondylosis of vertebral artery type is electroacupuncture + C4-C7 Jiaji (EX-B 2) + 5 min. The importance of different factors for the immediate effect in acupuncture treatment of cervical spondylosis of vertebral artery type is: acupoint selection > needling technique > time of needle retaining.

[Effect of moderate acupuncture-stimulation of "Taichong" (LR 3) on blood pressure and plasma endothelin-1 levels in spontaneous hypertension rats].

OBJECTIVE: To observe the effect of different strength of acupuncture stimulation on blood pressure and plasma endothelin (E)-1 in spontaneous hypertension rats (SHR) ,so as to seek a better acupuncture parameter for clinical treatment of hypertension. METHODS: Twenty-eight 9-week-old SHRs were randomized into mild-stimulation group, moderate-stimulation group, strong-stimulation group and model group (n = 7 in each group). Seven normotensive SD rats served as a normal control group. Acupuncture stimulation with mild, moderate and strong stimulation was applied to bilateral "Taichong" (LR 3) for 5 min, once daily for 7 days. Blood pressure (BP) was determined by using a non-invasive BP-6 detection system. Plasma ET-1 was assayed by radioimmunoassay. RESULTS: Compared with the model group, the systolic pressure of the moderate-stimulation group on the 6th and 7th day was decreased significantly after acupuncture of "Taichong" (LR 3) (P<0. 01), being significantly lower than that of the mild- and strong-stimulation groups (P<0. 01). In comparison with the normal control group, plasma ET-1 level in the model group was increased significantly (P<0.01), while compared with the model group, only that in the moderate-stimulation group was down-regulated considerably (P<0. 01). No significant differences were found between the mild-stimulation and model groups, between the strong-stimulation and model groups, and between the mild-stimulation and strong-stimulation groups in plasma ET-1 level (P>0. 05). CONCLUSION: Moderate-stimulation of "Taichong" (LR 3) can lower blood pressure and plasma EA-1 level in spontaneous hypertension rats. The reduced level of plasma ET-1 may be one of its mechanisms underlying improving hypertension.

A study on the classification and the 'catching' of the 'arrived qi' in acupuncture.

This essay studies the phenomenon of 'obtaining of qi' in acupuncture. Combined with clinical practice, the authors think that it was a habitual misunderstanding in the past to equate 'needling sensation' to 'obtaining of qi' in acupuncture practice. The two concepts are different and are related with each other. The authors have also classified the phenomenon of 'obtaining of qi' according to its depth in the skin layer. Based on the research achievements in neuroscience, the authors propose the study on 'catching' the specific cerebrations, so as to reveal the essence of 'obtaining of qi'.

[Effect of acupuncture treatment of relieving depression and regulating mind on insomnia accompanied with depressive disorders].

OBJECTIVE: To compare the therapeutic effects of insomnia accompanied with depressive disorders treated by acupuncture of relieving depression and regulating mind and oral administration of Trazodone. METHODS: Sixty-five cases were randomly divided into a acupuncture group (33 cases) and western medication group (32 cases). In acupuncture group, Shenmen (HT 7), Baihui (CV 20), Hegu (LI 4) and Taichong (LR 3) were selected. In western medication group, Trazodone was applied with oral administration for 4 weeks. The curative effect comparison was carried on by Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), and Side Effect Rating Scale (SERS) of Asberg. RESULTS: The cured and markedly effective rate of 72.7% (24/33)in acupuncture group was superior to that of 46.8% (15/32) in western medication group; after treatment, the scores of all items and the total cumulative scores of PSQI and SDS of both groups were reduced (P < 0.01, P < 0.05), of which, the sleep quality and daytime function evaluation in acupuncture group reduced more obviously than those in western medication group (both P < 0.05); the SERS scores of Asberg in western medication group were higher than those in acupuncture group. CONCLUSION: Acupuncture treatment of relieving depression and regulating mind is superior to Trazodone with oral administration for sleep quality and daytime function, with milder adverse reactions.

Substrate specificity, inhibitors and regulation of human cytochrome P450 2D6 and implications in drug development.

CYP2D6 accounts for only a small percentage of total hepatic CYPs (<2%), but it metabolizes approximately 25% of clinically used drugs (>100) with significant polymorphisms. A number of drugs acting on the central nervous system and cardiovascular system are substantially metabolized by CYP2D6. The enzyme also utilizes hydroxytryptamines and neurosteroids as endogenous substrates. In addition, CYP2D6 metabolizes procarcinogens and neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, and indolealkylamines. Typical CYP2D6 substrates are usually lipophilic bases with a planar hydrophobic aromatic ring and a nitrogen atom which can be protonated at physiological pH, but several atypical substrates such as spirosulfonamide and pactimibe do not contain a basic nitrogen atom. The structure of human CYP2D6 has been recently determined and shows the characteristic CYP fold as observed in other members of the CYP superfamily, with a well-defined active site cavity above the heme group with a volume of approximately 540 A(3). CYP2D6 is largely uninducible by prototypical CYP inducers such as phenobarbital, rifampin and dexamethasone, but it is regulated by hepatocyte nuclear factor-4alpha, a nuclear receptor. CYP2D6 is subject to inhibition by a number of drugs and this may provide an explanation for numerous clinical drug interactions. CYP2D6 has an important role in drug development and it is a common practice for pharmaceutical industry nowadays to a great extent screen drug candidates early in development as possible CYP2D6 substrates and/or inhibitors and drop such candidates where they have alternatives. This candidate selection might eventually lead to a less prominent role of this enzyme in the future for drug metabolism and less interindividual variability in drug exposure and minimize potentially adverse drug interactions. Further studies are warranted to delineate the molecular mechanisms involved in the function and regulation of CYP2D6.

[Functional brain magnetic resonance imaging in healthy people receiving acupuncture at Waiguan versus Waiguan plus Yanglingquan points: a randomized controlled trial].

OBJECTIVE: To observe the cerebral activating effects of needling at Waiguan (SJ5) versus SJ5 plus Yanglingquan (GB34) points in young healthy volunteers based on the hypothesis of "needling effect of combined acupuncture points relates to the brain activation". METHODS: Sixteen healthy volunteers were randomly divided into SJ5 group and SJ5 plus GB34 group, and there were 8 volunteers in each group. The volunteers in the two groups received needling at corresponding points on the right hand or foot respectively. Nuclear magnetic resonance (1.5T, GE Corporation) was used for functional magnetic resonance imaging (fMRI) of the brain before and during the needling, and the obtained experimental data in the regional brain were processed and analyzed by the method of region of interest (ROI). RESULTS: The ROI activation induced by needling of SJ5 or SJ5 plus GB34 was all relatively concentrated (activation rate more than 4 or activation point more than 10) on bilateral frontal and parietal lobes. There were no significant differences in ROI activation rates of brain regions between the two groups. ROI activation points showed that needling at SJ5 could activate the right cerebellum specifically (P < 0.05, vs SJ5 plus GB34), while needling at SJ5 plus GB34 could activate the left parietal and occipital lobes and bilateral basal ganglion more effectively than activate the other brain regions (P < 0.05, vs SJ5). ROI activation strength showed that needling at SJ5 plus GB34 could more strongly activate the right cerebellum (P < 0.05, vs SJ5). CONCLUSION: Based on fMRI data, a kind of acupuncture point combination of SJ5 and GB34 within the hand-foot Shaoyang meridians, could improve the motor and sensory dysfunctions and equilibrium disturbance. The effect of combined acupuncture points was proved by cerebral activity initially.

[Effect of electroacupuncture on learning-memory ability of vascular dementia rats with concomitant hypertension and hyperlipemia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of acupoint recipe for "dredging Governor-Meridian, regulating vitality and strengthening the kidney" on learning-memory ability and pathological changes of cerebral minute blood vessels and hippocampal structure in hypertension-hyperlipmia-vascular dementia (HH-VD) rats. METHODS: Forty SD rats were randomly divided into sham-operation (sham) group (n=8), EA-I group [n=8, EA of "Baihui" (GV 20), "Dazhui" (GV 14), "Pishu" (BL 20) and "Shenshu" (BL 23), 80 Hz, 1 mA, 20 min/day, 15 days], EA-II group (n=8, EA of nonpoints, 5 mm lateral to the abovementioned acupoints), medication group (n=8, intragastric perfusion of Nimotong, 0.6 mg/mL, 20 mL/kg, 15 days), model group (n=8). HH-VD model was established by feeding the rat with high fat forage and by occlusion of the left renal artery and carotid artery. The animals' learning-memory ability was detected by Y-maze test, the synaptic structure of the hippocampal CA 1 region, and the pathological change of the cerebral cortex were observed by electronic microscope and light microscope, respectively. RESULTS: After modeling, the blood pressure, serum total cholesterol and triglyceride (TG) levels, and the error number (EN), total reaction time (TRT) and standard number (SN, number of paw-electric-stroke for reaching correct reactions) of Y maze test increased significantly in comparison with sham group (P<0.05). After EA, the EN, TRT and SN of EA-I , EA-II and medication groups decreased significantly in comparison with model group (P<0.01), suggesting a striking improvement of the learning-memory ability after the treatment, and the EN, TRT and SN of EA-I group and medication group were significantly lower than those of EA-II group (P<0.05). Under electronic microscope, the number of synapses in hippocampal CA 1 area of HH-VD model rats reduced obviously, its postsynaptic density (PSD) was lighter, and the synaptic vesicles were fewer. Whereas in comparison with EA-II and medication groups, the synaptic number and density in EA-I group were more and bigger, and the width, length and color of PSD increased clearly. The synaptic number of EA-II group was relatively smaller compared with the other two treatment groups. Under light microscope, the vascular walls of the cerebral minute and small arteries of model group were obviously thickened and their lumina narrowed. While in EA-I group, these pathological changes were mild. In medication group the thickening of vascular walls of partial cerebral minute and small arteries were also seen. CONCLUSION: EA of acupoint recipe for "dredging Governor-Meridian, regulating vitality and strengthening the kidney" can improve pathological changes of the synaptic structure of hippocampal CA 1 region and the vascular walls of cerebral minute and small arteries, which may contribute to its function in improving the learning-memory ability in HH-VD rats.

Human CYP2C8: structure, substrate specificity, inhibitor selectivity, inducers and polymorphisms.

Human CYP2C8 is a key member of the CYP2C family and metabolizes more than 60 clinical drugs. A number of active site residues in CYP2C8 have been identified based on homology modeling and site-directed mutagenesis studies. In the structure of CYP2C8, the large active site cavity exhibits a trifurcated topology that approximates a T or Y shape, which is consistent with the finding that CYP2C8 can efficiently oxidize relatively large substrates such as paclitaxel and cerivastatin. The active site cavity of CYP2C8 contains at least 48 amino acid residues and many of them are important for substrate binding. The structures of CYP2C8 in complex with distinct ligands have revealed that the enzyme can bind divergent substrates and inhibitors without extensive conformational changes. CYP2C8 is a major catalyst in the metabolism of paclitaxel, amodiaquine, troglitazone, amiodarone, verapamil and ibuprofen, with a secondary role in the biotransformation of cerivastatin and fluvastatin. CYP2C8 also metabolises endogenous compounds such as retinoids and arachidonic acid. Many drugs are inhibitors of CYP2C8 and inhibition of this enzyme may result in clinical drug interactions. The pregnane X receptor, constitutive androstane receptor, and glucocorticoid receptor are likely to involve the regulation of CYP2C8. A number of genetic mutations in the CYP2C8 gene have been identified in humans and some of them have functional impact on the clearance of drugs. Further studies are needed to delineate the role of CYP2C8 in drug development and clinical practice.

Electroacupuncture treatment of chronic insomniacs.

BACKGROUND: Due to the quick rhythm of life and work pressure, more and more people suffer from sleep quality problems. In this study, we investigated the effect of electroacupuncture on sleep quality of chronic insomniacs and the safety of electroacupuncture therapy. METHODS: Four courses of electroacupuncture treatment were applied to 47 patients. With pre-treatment and post-treatment self-control statistical method, Pittsburgh sleep quality index (PSQI) scores were used for evaluating sleep quality. Polysomnogram was used for detecting insomniacs' changes in sleep architecture. The safety of electroacupuncture was evaluated by monitoring the self-designed adverse events and side effects during treatment and post-treatment. RESULTS: Electroacupuncture considerably improved insomniacs' sleep quality and social function during the daytime. Electroacupuncture had certain repairing effect on the disruption in sleep architecture. At the same time, electroacupuncture prolonged slow wave sleep (SWS) time and relatively rapid eye movement sleep (REM sleep) time. There was no hangover, addiction or decrements in vigilance during the daytime (incidence rate was 0). However, insomnia rebound rate was about 23% within one month. CONCLUSIONS: These results suggest that electroacupuncture has beneficial effect on sleep quality improvement in the patients with chronic insomnia, which may be associated with repairing sleep architecture, reconstructing sleep continuity, as well as prolonging SWS time and REM sleep time. Electroacupuncture treatment for chronic insomnia is safe. Therefore, electroacupuncture therapy could be a promising avenue of treatment for chronic insomnia.