Scorpion Venom Heat-Resistant Synthesized Peptide Increases Stress Resistance and Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1-Like Signal Pathway.

Improving healthy life expectancy by targeting aging-related pathological changes has been the spotlight of geroscience. Scorpions have been used in traditional medicine in Asia and Africa for a long time. We have isolated heat-resistant peptides from scorpion venom of Buthusmartensii Karsch (SVHRP) and found that SVHRP can attenuate microglia activation and protect Caenorhabditis elegans (C. elegans) against ß-amyloid toxicity. Based on the amino acid sequence of these peptides, scorpion venom heat-resistant synthesized peptide (SVHRSP) was prepared using polypeptide synthesis technology. In the present study, we used C. elegans as a model organism to assess the longevity-related effects and underlying molecular mechanisms of SVHRSP in vivo. The results showed that SVHRSP could prolong the lifespan of worms and significantly improve the age-related physiological functions of worms. SVHRSP increases the survival rate of larvae under oxidative and heat stress and decreases the level of reactive oxygen species and fat accumulation in vivo. Using gene-specific mutation of C. elegans, we found that SVHRSP-mediated prolongation of life depends on Daf-2, Daf-16, Skn-1, and Hsf-1 genes. These results indicate that the antiaging mechanism of SVHRSP in nematodes might be mediated by the insulin/insulin-like growth factor-1 signaling pathway. Meanwhile, SVHRSP could also up-regulate the expression of stress-inducing genes Hsp-16.2, Sod-3, Gei-7, and Ctl-1 associated with aging. In general, our study may have important implications for SVHRSP to promote healthy aging and provide strategies for research and development of drugs to treat age-related diseases.

Reducing Nav1.6 expression attenuates the pathogenesis of Alzheimer's disease by suppressing BACE1 transcription.

Aberrant increases in neuronal network excitability may contribute to cognitive deficits in Alzheimer's disease (AD). However, the mechanisms underlying hyperexcitability of neurons are not fully understood. Voltage-gated sodium channels (VGSC or Nav), which are involved in the formation of excitable cell's action potential and can directly influence the excitability of neural networks, have been implicated in AD-related abnormal neuronal hyperactivity and higher incidence of spontaneous non-convulsive seizures. Here, we have shown that the reduction of VGSC α-subunit Nav1.6 (by injecting adeno-associated virus (AAV) with short hairpin RNA (shRNA) into the hippocampus) rescues cognitive impairments and attenuates synaptic deficits in APP/PS1 transgenic mice. Concurrently, amyloid plaques in the hippocampus and levels of soluble Aß are significantly reduced. Interfering with Nav1.6 reduces the transcription level of ß-site APP-cleaving enzyme 1 (BACE1), which is Aß-dependent. In the presence of Aß oligomers, knockdown of Nav1.6 reduces intracellular calcium overload by suppressing reverse sodium-calcium exchange channel, consequently increasing inactive NFAT1 (the nuclear factor of activated T cells) levels and thus reducing BACE1 transcription. This mechanism leads to a reduction in the levels of Aß in APP/PS1 transgenic mice, alleviates synaptic loss, improves learning and memory disorders in APP/PS1 mice after downregulating Nav1.6 in the hippocampus. Our study offers a new potential therapeutic strategy to counteract hippocampal hyperexcitability and subsequently rescue cognitive deficits in AD by selective blockade of Nav1.6 overexpression and/or hyperactivity.

Corrigendum: Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation.

[This corrects the article DOI: 10.3389/fphar.2021.704715.].

Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation.

Background: Intervention of neuroinflammation in central nervous system (CNS) represents a potential therapeutic strategy for a host of brain disorders. The scorpion Buthus martensii Karsch (BmK) and its venom have long been used in the Orient to treat inflammation-related diseases such as rhumatoid arthritis and chronic pain. Scorpion venom heat-resistant peptide (SVHRP), a component from BmK venom, has been shown to reduce seizure susceptibility in a rat epileptic model and protect against cerebral ischemia-reperfusion injury. As neuroinflammation has been implicated in chronic neuronal hyperexcitability, epileptogenesis and cerebral ischemia-reperfusion injury, the present study aimed to investigate whether SVHRP has anti-inflammatory property in brain. Methods: An animal model of neuroinflammation induced by lipopolysacchride (LPS) injection was employed to investigate the effect of SVHRP (125 µg/kg, intraperitoneal injection) on inflammagen-induced expression of pro-inflammatory factors and microglia activation. The effect of SVHRP (2-20 µg/ml) on neuroinflammation was further investigated in primary brain cell cultures containing microglia as well as the immortalized BV2 microglia culture stimulated with LPS. Real-time quantitative PCR were used to measure mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6 in hippocampus of animals. Protein levels of TNF-α, iNOS, P65 subunit of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) were examined by ELISA or western blot. Microglia morphology in animal hippocampus or cell cultures and cellular distribution of p65 were shown by immunostaining. Results: Morphological study demonstrated that activation of microglia, the main component that mediates the neuroinflammatory process, was inhibited by SVHRP in both LPS mouse and cellular model. Our results also showed dramatic increases in the expression of iNOS and TNF-α in hippocampus of LPS-injected mice, which was significantly attenuated by SVHRP treatment. In vitro results showed that SVHRP attenuated LPS-elicited expression of iNOS and TNF-α in different cultures without cell toxicity, which might be attributed to suppression of NF-κB and MAPK pathways by SVHRP. Conclusion: Our study demonstrates that SVHRP is able to inhibit neuroinflammation and microglia activation, which may underlie the therapeutic effects of BmK-derived materials, suggesting that BmK venom could be a potential source for CNS drug development.

Comparison of Pharmacokinetics and Tissue Distribution Characteristics of Three Diterpenoid Esters in Crude and Prepared Semen Euphorbiae.

BACKGROUND: Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP) have a long history of medicinal use. SEP is the processed product of SE; both ancient and modern studies have shown that SEP has a lower toxicity compared to SE. To clarify the influence of processing on the pharmacological properties of SE and SEP, a study was carried out to compare the pharmacokinetics and distribution characteristics of three active compounds after oral administration of SE and SEP extracts. METHODS: A UPLC-MS/MS method was established to simultaneously determine the contents of Euphorbia factors L1, L2, and L3 in rat plasma and mouse tissues after an oral administration of crude and processed SE with approximately the same dosage. Plasma and heart, liver, spleen, lung, kidney, and colon tissue samples were treated with ethyl acetate and separated by gradient elution on a C18 column with a mobile phase of 0.1% formic acid and methanol. RESULTS: The established method had good selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery. The area under the concentration time curve, time to maximum concentration, maximum concentration, half-life of elimination, and mean retention time of plasma samples in SEP-treated group decreased, and the clearance in SEP-treated group increased. Moreover, the active component concentrations in colon, liver, and kidney tissues were more followed by those in the heart, lungs, and spleen. CONCLUSION: These results indicate that the processing could influence the pharmacokinetics and tissue distribution of Euphorbia factors L1, L2, and L3 after oral administration of crude and processed SE. The data obtained may lay a foundation for the clinical use of SE and for further study on the processing mechanism of SE.

Endophytic Bacillus amyloliquefaciens YTB1407 elicits resistance against two fungal pathogens in sweet potato (Ipomoea batatas (L.) Lam.).

The endophytic Bacillus amyloliquefaciens YTB1407 was previously reported to promote the growth of sweet potato (Ipomoea batatas cv. Yanshu 25). Here, we demonstrate in both in vitro and pot trial assays that pre-treatment with YTB1407 suspension could enhance resistance against root rot disease and black rot disease, caused by Fusarium solani Mart. Sacc. f. sp. batatas McClure and Ceratocystis fimbriata Ell. & Halst on sweet potato, respectively. When seedlings were infected with fungal pathogens at 10 days post irrigation, pre-treatment with YTB1407 suspension decreased these pathogens and YTB1407 bacterial biomass in sweet potato roots. The pre-treatment activated the expression of salicylic acid (SA)-responsive PR-1 gene, raised SA content, and reduced hydrogen peroxide (H2O2) in the host to resist F. solani, while it enhanced the expression levels of SA-responsive NPR1 and PR1 genes and increased SA content to resist C. fimbriata. The disease resistance control effect initiated by pre-treatment with YTB1407 for root rot pathogen (F. solani) was better than for black rot pathogen (C. fimbriata). The results indicated that Bacillus amyloliquefaciens YTB1407 played a pivotal role in enhancing resistance to two fungi pathogens in sweet potato, through production of some antifungal metabolites to decrease infection in the early stage as well as induction of SA-dependent systemic resistance.

Scorpion Venom Heat-Resistant Peptide is Neuroprotective against Cerebral Ischemia-Reperfusion Injury in Association with the NMDA-MAPK Pathway.

Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Our previous studies have shown that SVHRP is neuroprotective in models of Alzheimer's disease and Parkinson's disease. The present study aimed to explore the potential neuroprotective effects of SVHRP on cerebral ischemia/reperfusion (I/R) injury, using a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R). Our results showed that SVHRP treatment decreased the neurological deficit scores, edema formation, infarct volume and neuronal loss in the MCAO/R mice, and protected primary neurons against OGD/R insult. SVHRP pretreatment suppressed the alterations in protein levels of N-methyl-D-aspartate receptors (NMDARs) and phosphorylated p38 MAPK as well as some proinflammatory factors in both the animal and cellular models. These results suggest that SVHRP has neuroprotective effects against cerebral I/R injury, which might be associated with inhibition of the NMDA-MAPK-mediated excitotoxicity.

[Root promoting effect and its regulation mechanisms of endophytic Bacillus amyloliquefaciens YTB1407 in sweet potato]. / å† ç”Ÿåž‹è§£æ·€ç²‰èŠ½å­¢æ†èŒYTB1407å¯¹ç”˜è–¯æ ¹ç³»çš„ä¿ƒç”Ÿä½œç”¨åŠå ¶è°ƒæŽ§æœºç†.

We isolated the endophytic Bacillus amyloliquefaciens YTB1407 from the root of Panax quinquefolium, which has both biological control and growth promoting effects. To investigate its potential applications, a pot experiment of sweet potato was tested to assess the capacity of endophytic colonization of YTB1407 and the selection of its optimum concentration by investigating the performance of root characteristics on three time points in the whole early growth phase after irrigating with different concentrations of bacterial suspensions with treatment of sterile water as control. The activities of endogenous hormone IAA, ZR, t-ZR and IAA oxidase (IAAO, PPO, POD) were analyzed. The results showed that YTB1407 promoted the specific colonization of root system, the elongation of adventitious root and branch roots, and root activity in the early growth stage of sweet potato. At later growth stage, it formed greater fresh mass of absorption root and lower aboveground/root system mass ratio. YTB1407 suspensions with OD600 of 0.50 (T0.50) had more significant effect, which induced the highest fresh tuber mass and the largest effective tuber numbers of per plant at top cover stage. YTB1407 promoted the differentiation of adventitious roots into tubers at initial point of tuberization by increasing IAA content and the ratio of (t-ZR+ZR)/IAA, decreasing IAAO activity and enhancing PPO activity. Moreover, it promoted the differentiated roots into tubers at tuberization stage by keeping the higher content of IAA, lower ratio of (t-ZR+ZR)/IAA, and decreasing IAAO and PPO activities.

The generation and biological activity of a long-lasting recombinant human interferon-λ1.

The previously generated recombinant human (rh) interferon (IFN)-λ1 protein has a short half-life, and this feature makes it challenging to conduct studies on potential clinical applications for rhIFN-λ1. In an attempt to overcome this difficulty, we constructed a 'long-life' version of rhIFN-λ1. This modified rhIFN-λ1, named rhIFN-λ1-CTPON, has a human chorionic gonadotropin ß subunit carboxyl-terminal peptide (CTP) and an N-glycosylation sequence linked to its C-terminus. We confirmed the sequence of rhIFN-λ1-CTPON by mass spectrometry and then measured its biological activities. The results show that rhIFN-λ1-CTPON had antiviral activity and anti-proliferation activity in vitro that were similar to those of rhIFN-λ1 and that it similarly promoted natural killer cell cytotoxicity. Notably, the in vivo half-life of rhIFN-λ1-CTPON was determined to be 3-fold higher than that of rhIFN-λ1. We also assessed the anti-hepatitis B virus activity of rhIFN-λ1-CTPON; it was able to inhibit the production of the antigens HBs-Ag and HBe-Ag and induce antiviral gene expression. In conclusion, rhIFN-λ1-CTPON has a longer half-life than rhIFN-λ1 and has similar biological activities, so rhIFN-λ1-CTPON is an appropriate substitute for rhIFN-λ1 in the further study of potential clinical applications for rhIFN- λ1.

Effect of gap junctions on RAW264.7 macrophages infected with H37Rv.

BACKGROUND: Apoptosis and inflammation have been shown to play an important role in the mechanisms involved in the pathogenesis of Mycobacterium tuberculosis (MTB) infection. When macrophages undergo apoptosis and polarization, gap junctions (GJs) may be needed to provide conditions for their functions. Connexin 43 (Cx43) and connexin 37 (Cx37) are the main connexins in macrophages that participate in the formation of GJ channels. METHODS: An H37Rv infection RAW264.7 macrophage model was established to investigate the associate between connexins and host macrophage immune defense response after MTB infection. First, Real-time Polymerase Chian Reaction (RT-PCR) was used to detect the mRNA expression of Cx43 and Cx37. Cx43 protein expression and location was detected by western blotting and immunofluorescence. Confocal microscope was used to assay the gap junctional intercellular communication (GJIC). Then, electron microscope used to observe the morphology of macrophages. Finally, RAW264.7 macrophage apoptosis and mitochondrial membrane potential was detected by flow cytometry, and the expression of inflammation factors such as CD86, CD206, and IL-6, IL-10, TNF-α, and TGF-ß were detected by Real-time PCR and enzyme-linked-immunosorbent serologic assay (ELISA). RESULTS: H37Rv infection significantly promoted host macrophage Cx43 mRNA and protein expression (increased 1.6-fold and 0.3-fold respectively), and enhanced host macrophage GJIC. When host macrophage cell-to-cell communication induced by H37Rv infection, the apoptosis rate and inflammatory factors expression also increased. CONCLUSIONS: The results confirm that H37Rv infection can obviously induce host macrophage Cx43 expression and enhance GJIC, which may implicated in host macrophage inflammatory reaction, to regulate the release of inflammatory factors and/or initiate apoptosis to activate host immune defense response.

[Influence of fixed orthodontic treatment on oral health-related quality of life in adolescent and adult: a comparative study].

PROPOSE: To compare the changes in oral health-related quality of life(OHRQoL) among adolescent patients and adult patients during orthodontic treatment. METHODS: The clinical data were collected from 81 patients (aged 15 to 25 years old) who underwent comprehensive orthodontic treatment. The participants were divided into 2 groups: adolescent patients (n=43) and adult patients (n=38) by age. OHRQoL was assessed using the Oral Health Impact Profile (OHIP-14). All subjects were examined and interviewed at baseline and the end of 3 stages during orthodontics treatment. Friedman 2-way analysis of variance (ANOVA) and Wilcoxon signed rank tests were used to compare the relative changes of OHRQoL among different time points with SPSS 20.0 software package. RESULTS: The scores of OHIP-14 and all domains except communication disorder and social disability domain in adolescent and adult patients showed significant changes as well as a decrease trend. Only adults showed significant changes in communication disorder.Both groups had no significant difference. CONCLUSIONS: The impact of comprehensive orthodontic treatment on patients' OHRQoL is quite different. Orthodontists should pay attention to the differences and guide the patients accordingly.

Expression of AQP2, AQP4 and AQP 8 in mouse intestine induced by unprocessed and processed Euphorbia lathyris.

The present research was designed to study expression of AQP2, AQP4 and AQP8 in mouse intestines induced by unprocessed and processed Euphorbia lathyris. KM mice were given by different dose lavage of unprocessed and processed Euphorbia lathyris, Euphorbia factor L1, Euphorbia factor L2, Euphorbia factor L3. Samples of mouse intestine were collected for protein levels of AQP2, AQP 4 and AQP 8 which were assessed by immunohistochemical staining and mRNA expression of AQP2, AQP 4 and AQP 8 which were quantified by Real Time-PCR. Comparing to the normal control group, the protein levels of AQP2, AQP 4 and AQP 8 were significantly decreased (P<0.05)by Semen Euphorbiae group and Semen Euphorbiae Pulveratum group (unprocessed and processed Euphorbia lathyris) induced. Protein expression of AQP2, AQP 4 and AQP 8 in the Euphorbia factor L1, Euphorbia factor L2 and Euphorbia factor L3 group were not significantly lower than normal control group. There had no differences on the levels of AQP2 and AQP 8 mRNA expressions between the high-dose group of semen Euphorbiae group, semen Euphorbiae Pulveratum group and positive control group, while significantly lower than normal control group (P<0.05). Expression of AQP4 mRNA in the Semen Euphorbiae group and Semen Euphorbiae Pulveratum group has not significantly decreased. But levels of AQP2, AQP 4 and AQP 8 mRNA in the Euphorbia factor L1 group had no significant differences in normal control group and positive control group. These findings suggest that semen Euphorbiae could regulate expression of AQP2, AQP 4 and AQP 8 protein and mRNA, which may be the possible one reason of semen Euphorbiae induces diarrhea. The semen Euphorbiae group has more significant effects on the levels of AQP2, AQP 4 and AQP 8 protein and mRNA than semen Euphorbiae Pulveratum group, which may be one of the mechanisms of processing attenuation.

Bioactivation of cyclopropyl rings by P450: an observation encountered during the optimisation of a series of hepatitis C virus NS5B inhibitors.

1. Due to its unique C-C and C-H bonding properties, conformational preferences and relative hydrophilicity, the cyclopropyl ring has been used as a synthetic building block in drug discovery to modulate potency and drug-like properties. During an effort to discover inhibitors of the hepatitis C virus non-structural protein 5B with improved potency and genotype-coverage profiles, the use of a pyrimidinylcyclopropylbenzamide moiety linked to a C6-substituted benzofuran or azabenzofuran core scaffold was explored in an effort to balance antiviral potency and metabolic stability. 2. In vitro metabolism studies of two compounds from this C6-substituted series revealed an NADPH-dependent bioactivation pathway leading to the formation of multiple glutathione (GSH) conjugates. Analysis of these conjugates by LC-MS and NMR demonstrated that the cyclopropyl group was the site of bioactivation. Based on the putative structures and molecular weights of the cyclopropyl-GSH conjugates, a multi-step mechanism was proposed to explain the formation of these metabolites by P450. This mechanism involves hydrogen atom abstraction to form a cyclopropyl radical, followed by a ring opening rearrangement and reaction with GSH. 3. These findings provided important information to the medicinal chemistry team which responded by replacing the cyclopropyl ring with a gem-dimethyl group. Subsequent compounds bearing this feature were shown to avert the bioactivation pathways in question.

Enhanced gap junctional channel activity between vascular smooth muscle cells in cerebral artery of spontaneously hypertensive rats.

The aim of the present study is to investigate the effects of hypertension on the gap junctions between vascular smooth muscle cells (VSMCs) in the cerebral arteries (CAs) of spontaneously hypertensive rats (SHRs). The functions of gap junctions in the CAs of VSMCs in SHRs and control normotensive Wistar-Kyoto (WKY) rats were studied using whole-cell patch clamp recordings and pressure myography, and the expression levels of connexins were analyzed using reverse transcription-quantitative polymerase chain reaction and Western blot analyses. Whole-cell patch clamp measurements revealed that the membrane capacitance and conductance of in situ VSMCs in the CAs were significantly greater in SHRs than in WKY rats, suggesting that gap junction coupling is enhanced between VSMCs in the CAs of SHRs. Application of the endothelium-independent vasoconstrictors KCl or phenylephrine (PE) stimulated a greater vasoconstriction in the CAs of SHRs than in those of WKY rats. The EC50 value of KCl was 24.9 mM (n = 14) and 36.9 mM (n=12) for SHRs and WKY rats, respectively. The EC50 value of PE was 0.9 µM (n = 7) and 2.2 µM (n = 7) for SHRs and WKY rats, respectively. Gap junction inhibitors 18ß-glycyrrhetinic acid (18ß-GA), niflumic acid (NFA), and 2-aminoethoxydiphenyl borate (2-APB) attenuated KCl-induced vasoconstriction in SHRs and WKY rats. The mRNA and protein expression levels of the gap junction protein connexin 45 (Cx45) were significantly higher in the CAs of SHRs than in those of WKY rats. Phosphorylated Cx43 protein expression was significantly higher in the CAs of SHRs than in those of WKY rats, despite the total Cx43 mRNA and protein expression levels in the cerebral artery (CA) exhibiting no significant difference between SHRs and WKY rats. Increases in the expression of Cx45 and phosphorylation of Cx43 may promote gap junction communication among VSMCs in the CAs of SHRs, which may enhance the contractile response of the CA to vasoconstrictors.

Association of connexin gene polymorphism with essential hypertension in Kazak and Han Chinese in Xinjiang, China.

Essential hypertension (EH) is affected by both genetic and environmental factors. The polymorphism of connexin (Cx) genes is found associated with the development of hypertension. However, the association of the polymorphism of Cxs with EH has not been investigated. This study aimed to investigate the association of the polymorphism of connexin (Cx) genes Cx37, Cx40, and Cx43 with EH in Kazak and Han Chinese in Xinjiang, China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to analyze the polymorphism of Cx genes in Kazak and Han EH patients as well as their normotensive controls. The results showed that there were no significant differences in the frequencies of different three genotypes (A/A, A/G, and G/G) and A and G alleles of Cx40 rs35594137 and rs11552588 between EH patients and normotensive controls. However, in Kazak EH patients, the frequencies of three genotypes (A/A, A/G, and G/G) of Cx37 rs1630310 were 24.8%, 47.2% and 28.0%, respectively, which were significantly different from those in Han EH patients. In Han EH patients, the frequencies of the three genotypes (C/C, C/G and G/G) of Cx43 rs1925223 were 6.4%, 35.6% and 58.0%, respectively. Frequencies of the other four genotypes had no statistical differences among Kazak and Han EH patients and their normotensive controls. These results suggest polymorphisms of Cx37 rs1630310 and Cx43 rs1925223 genes may be associated with the pathogenesis of EH. Carrying Cx37 rs1630310-A or Cx43 rs1925223-G genotypes may protect against the development of EH.

[Chromatographic fingerprint analysis of Toosendan Fructus by HPLC-CAD coupled with chemometrics methods].

A new method was developed for the chromatographic fingerprint analysis of Toosendan Fructus by HPLC coupled with the charged aerosol detector (CAD) in the present study. Samples were well separated on an Agilent ZOBAX SB C18 column (4.6 mm × 250 mm, 5 µm) by gradient elution using acetonitrile and water containing 0.1 % formic acid (v/v) at the flow rate of 1.0 mL·min−1. The column temperature was 30 ℃ and the injection volume was 5 µL. The nitrogen inlet pressure of the charged aerosol detector (CAD) was 35 psi, and the nebulizer chamber temperature was 35 ℃. In addition, the method of the chromatographic fingerprints combined with multivariate statistical analysis was effective and reasonable lead to an accurate classification of 20 batches of samples from different locations. The results showed that 28 common peaks were observed in the fingerprint and the samples were classified into three clusters. The established method was well validated, and showed high precision, good repeatability, and satisfactory stability. It may serve in the quality control and evaluation of Toosendan Fructus.

[Effect of icraiin on turnover of alveolar bone during orthodontic tooth movement in rats].

PURPOSE: To observe the effect of icariin on turnover of paradentium as well as the mechanism of effects on osteoclast during orthodontic tooth movement in rats. METHODS: Forty-right SD rats were used to establish animal models of OTM and divided into two groups randomly: the control group and the experimental group. Rats in the experimental group were given 20 mg/（kg.d） icariin by intragastric administration, while rats in the control group received solvent with the same volume. The rats were sacrificed in batch on the 7th, 14th, 21st and 28th day after orthodontic treatment. The amount of tooth movement was measured, and histomorphometric analysis based on slices from periodontium adjacent to the maxillary first molars was used to observe new bone formation, bone resorption and quantify osteoclasts. Statistical analysis was performed by using SPSS 16.0 software package. RESULTS: The movement distance of the first molar was significantly larger in the icariin group than that in the control group (P<0.05). In the icariin group, the number of osteoclasts was significantly higher than the control group at the 7th day and then demonstrated a steady decrease. CONCLUSIONS: Icariin could accelerate OTM in rats through promoting bone turnover of alveolar bone.

[Standardization of production of process Notopterygii Rhizoma et Radix slices].

Notopterol, isoimperatorin, volatile oil and extract （water and ethanol) were used as the research objects in this study to investigate the effects of different softening method, slice thickness and drying methods on the quality of Notopterygii Rhizoma et Radix slices, and the experimental data were analyzed by homogeneous distance evaluation method. The results showed that different softening, cutting and drying processes could affect the content of five components in Notopterygii Rhizoma et Radix incisum. The best processing technology of Notopterygii Rhizoma et Radix slices was as follows: non-medicinal parts were removed; mildewed and rot as well as moth-eaten parts were removed; washed by the flowing drinking water; stacked in the drug pool; moistening method was used for softening, where 1/8 volume of water was sprayed for every 1 kg of herbs every 2 h; upper part of herbs covered with clean and moist cotton, and cut into thick slices (2-4 mm) after 12 h moistening until appropriate softness, then received blast drying for 4 h at 50 ℃, and turned over for 2 times during the drying. The process is practical and provides the experimental basis for the standardization of the processing of Notopterygii Rhizoma et Radix, with great significance to improve the quality of Notopterygii Rhizoma et Radix slices.

[Preliminary study on standardization of production and processing of Angelicae Sinensis Radix pieces].

Study on the standardization of Chinese materia medica is an important action for modernization and globalization for traditional Chinese medicine. Standardization on the processing of Chinese herbal pieces is an important part in the study on standardization of Chinese materia medica, so it is of great significance to establish the technical processing standards of Angelicae Sinensis Radix pieces for improving its quality. In this study, single factor experiment was designed to optimize the softening, cutting and drying processes of Angelicae Sinensis Radix. With ferulic acid, Angelicae Sinensis Radix polysaccharide, volatile oil and extracts (water and ethanol) content as the quality index, the effects of different softening, cutting and drying processes on the contents of the five components in Angelicae Sinensis Radix were analyzed, and the normalized distance evaluation method was used to analyze the experimental data. The results showed that the content of five components in Angelicae Sinensis Radix was affected by different softening methods and drying temperature, but the thickness of slice had little effect on the content. The best preparation process for Angelicae Sinensis Radix was as follows: Non-medicinal parts were removed; mildewed and rot as well as moth-eaten parts were removed; washed by the flowing drinking water; stacked in the drug pool; moistening method was used for softening, where 125 mL water was sprayed for every 1 kg of herbs every 2.5 h; upper part of herbs covered with clean and moist cotton, and cut into thin slices (1-2 mm) after 15 h moistening until appropriate softness, with disk thickness of 1-2 cm, then received blast drying for 6 h at 55 ℃, and turned over for 2 times during the drying.

Association of Connexin Gene Polymorphism with Essential Hypertension in Kazak and Han Chinese in Xinjiang, China / 华中科技大学学报（医学）（英德文版）

Essential hypertension (EH) is affected by both genetic and environmental factors.The polymorphism of connexin (Cx) genes is found associated with the development of hypertension.However,the association of the polymorphism of Cxs with EH has not been investigated.This study aimed to investigate the association of the polymorphism of connexin (Cx) genes Cx37,Cx40,and Cx43 with EH in Kazak and Han Chinese in Xinjiang,China.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to analyze the polymorphism of Cx genes in Kazak and Han EH patients as well as their normotensive controls.The results showed that there were no significant differences in the frequencies of different three genotypes (A/A,A/G,and G/G) and A and G alleles of Cx40 rs35594137 and rs11552588 between EH patients and normotensive controis.However,in Kazak EH patients,the frequencies of three genotypes (A/A,A/G;and G/G) of Cx37 rs1630310 were 24.8％,47.2％ and 28.0％,respectively,which were significantly different from those in Han EH patients.In Han EH patients,the frequencies of the three genotypes (C/C,C/G and G/G) of Cx43 rs1925223 were 6.4％,35.6％ and 58.0％,respectively.Frequencies of the other four genotypes had no statistical differences among Kazak and Hart EH patients and their normotensive controls.These results suggest polymorphisms of Cx37 rs 1630310 and Cx43 rs 1925223 genes may be associated with the pathogenesis of EH.Carrying Cx37 rs1630310-A or Cx43 rs1925223-G genotypes may protect against the development of EH.