Study on the regulatory effect of herbal cake- partitioned moxibustion on colonic CD206, AMPK and TSC2 in rats with Crohn disease / 针灸推拿医学（英文版）

Objective: To explore the mechanism of herbal cake-partitioned moxibustion in Crohn disease (CD) treatment by observing the effect of herbal cake-partitioned moxibustion on protein expressions of colonic M2 macrophage marker CD206, AMP-activated protein kinase (AMPK) and tuberous sclerosis complex (TSC) 2. Methods: Twenty-six specific pathogen free male rats were randomly divided into a normal group, a model group and a herbal cake-partitioned moxibustion group. The CD model was prepared by enema with the mixture of 5％ (W/V) 2,4,6- trinitrobenzene sulfonic acid (TNBS) and 50％ ethanol at 2:1 (volume ratio). After the model was successfully prepared, rats in the herbal cake-partitioned moxibustion group received herbal cake-partitioned moxibustion at Qihai (CV 6) and bilateral Tianshu (ST 25). Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of rat colon; immunohistochemical technique was used to detect the expression of colonic CD206 protein; Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) technologies were used to detect the protein and mRNA expressions of colonic AMPK and TSC2. Results: Compared with the normal group, rats in the model group showed damaged colonic mucosa, missing of the epithelial layer, thickened submucosa, vascular proliferation, massive infiltration of monocytes and lymphocytes, and cracked ulcers that reached the muscle layer. Rats in the herbal cake-partitioned moxibustion group showed reduced intestinal inflammation and healing intestinal epithelium ulcers. Compared with the normal group, rat colonic CD206 protein expression, and the protein and mRNA expressions of colonic AMPK and TSC2 were decreased in the model group (all P<0.01); compared with the model group, rat colonic CD206 protein expression was increased (P<0.01), as well as the protein and mRNA expressions of AMPK and TSC2 in the herbal cake-partitioned moxibustion (all P<0.05). Conclusion: Herbal cake-partitioned moxibustion can reduce intestinal inflammation in CD rats, increase colonic CD206 protein expression, and up-regulate the protein and mRNA expressions of colonic AMPK and TSC2.

Association between apolipoprotein E polymorphism and myocardial infarction in patients with type 2 diabetes mellitus / 中华检验医学杂志

Objective:To investigate the relationship between the E2 and E4 alleles of apolipoprotein E (apoE) gene and myocardial infarction (MI) in type 2 diabetes Mellitus (T2DM) patients, and to explore the relationship between apoE polymorphism and blood lipid metabolism.Methods:This case control study was conducted from August 2016 to March 2020 in China-Japan Friendship Hospital, 3 459 inpatients with T2DM were included including 3 044 patients without MI (T2DM group) and 415 patients with MI (T2DM+MI group). Real time fluorescent quantitative PCR was used to detect apoE polymorphism. Automatic biochemical analyzer was used to detect lipid levels. Logistic regression analyses were performed to determine the association of apoE with risk of MI in patients with T2DM.Results:(1) The frequency of E4 allele in T2DM+MI group (12.29%, 102/830) was significantly higher than in T2DM group (9.13%,556/6 088), while the frequency of E2 allele in T2DM+MI group (7.35%,61/830) was significantly lower than that in T2DM group (8.21%,500/6 088), P=0.012. Logistic regression analyses showed that E4 allele carrier (E3/E4+E4/E4) faced a higher risk for MI in T2DM patients ( OR=1.48, 95% CI 1.14-1.92, P=0.003), while E2 allele carrier(E2/E3+E2/E2)did not face a higher risk of MI in T2DM patients ( OR=0.88, P=0.642). (2) The levels of apoE polymorphism and blood lipid: The levels of TC, LDL-C and apoB increased in the order of E4 allele, wild type and E2 allele ( P<0.05). The levels of HDL-C, apoA1 and apoE decreased in the order of E4 allele, Wild type and E2 allele ( P<0.05). Conclusion:The E4 allele is a risk factor for MI in T2DM patients, and apoE polymorphism can affect blood lipid level in this patent cohort.

Chaetocin:a review of its anticancer potential and mechanisms / 中国药理学与毒理学杂志

Chaetocin is a natural metabolite product with various biological activities and pharmacological functions isolated from Chaetomium species fungi belonging to the thiodiketopyrazines. Numerous studies have demonstrated a wide range of antitumor activities of chaetocin in vitro and in vivo. Several studies have demonstrated that chaetocin sup?presses the growth and proliferation of various tumour cells by regulating multiple signalling pathways related to tumour initiation and progression, inducing cancer cell apoptosis (intrinsic and extrinsic), enhancing autophagy, inducing cell cycle arrest, as well as inhibiting tumour angiogenesis, invasion and migration. The antitumor effects and molecular mechanisms of chaetocin are reviewed and analysed in this paper, and the prospective applications of chaetocin in cancer prevention and therapy are also discussed. Our review provides the theoretical basis for exploiting the clinical applica?tion of chaetocin in cancer treatment.

Chemical constituents of Psidium guajava and their antitumor and antifungal activities / 中国中药杂志

Twenty-six compounds, including sixteen meroterpenoids(1-16), a triterpenoid(17), four terpenoid derivatives(18-21), and five aromatic compounds(22-26), were isolated from the leaves of Psidium guajava. Their structures were identified by spectroscopic analyses including NMR and MS. Compounds 21-26 were obtained from plants of Psidium for the first time. Based on the structure,(R)-2-ethylhexyl 2H-1,2,3-triazole-4-carboxylate(24 a), an α-glucosidase inhibitor recently isolated from Paramignya trimera, should be revised as compound 24. Meroterpenoids 1-16 were evaluated for their antitumor and antifungal activities. Meroterpenoids psiguajadial D(4), guapsidial A(5), 4,5-diepipsidial A(7), guadial A(14), and guadial B(15) showed cytotoxicities against five human tumor cell lines(HL-60, A-549, SMMC-7721, MCF-7, and SW-480), among which 5 was the most effective with an IC_(50) of 3.21-9.94 μmol·L~(-1).

Spectrum and indications of acupuncture and moxibustion therapy based on bibliometric analysis / 中国针灸

OBJECTIVE@#To analyze the literature of acupuncture and moxibustion for diseases in the recent 5 years, and discuss the spectrum and indications of acupuncture and moxibustion.@*METHODS@#The literature on acupuncture and moxibustion for diseases in CNKI, Wanfang and VIP databases from January 1, 2015 to December 31, 2019 was searched, summarized and analyzed, and the disease spectrum was summarized. At the same time, the literature from 2015 to 2019 (group A), 1978 to 2005 (group B), and 1949 to 2005 (group C) was compared, and the indications of acupuncture and moxibustion therapy were summarized.@*RESULTS@#There were 32 011 articles on acupuncture and moxibustion for diseases in the recent 5 years, including 377 kinds of indications. These indications can be mostly classified as neurology (9384), orthopedics and traumatology (7765), gastroenterology (3529) and obstetrics and gynecology (2283). The types of diseases were mostly gastroenterology (52 types), neurology (47 types), ophthalmology and otorhinolaryngology (47 types), and obstetrics and gynecology (42 types). The first-class indications of acupuncture and moxibustion therapy in the recent 5 years were hemiplegia, lumbar disc herniation, cervical spondylosis, knee osteoarthritis, insomnia, constipation and cerebrovascular diseases; the second-class were facial neuritis, shoulder pain and headache; the third-class were dysphagia, dysmenorrhea and depression; the forth-class were asthma, urinary retention, cerebral palsy, hypertension, dementia, side effects of radiotherapy and chemotherapy, infertility, allergic rhinitis, vertigo, shoulder-hand syndrome, diabetic neuropathy, herpes zoster, pain, hiccup, diarrhea, lumbar sprain and sciatica.@*CONCLUSION@#Although the disease spectrum and indications of acupuncture and moxibustion therapy have changed to some extent in the recent 5 years, neurology and orthopedics and traumatology are still predominant, and the observation objects tend to transition from symptoms to diseases.

Treatment of irreducible femoral intertrochanteric fractures using a wire-guided device / 中华创伤杂志(英文版)

PURPOSE@#Treatment of irreducible femoral intertrochanteric fractures often requires open reduction. However, the technique unavoidably causes patients to suffer greater trauma. As such, minimally invasive techniques should be employed to reduce the surgical-related trauma on these patients and maintain a stable reduction of the fractures. Herein, a minimally invasive wire introducer was designed and used for the treatment of femoral intertrochanteric fractures. The effectiveness of using a wire-guided device to treat irreducible femoral intertrochanteric fractures was evaluated.@*METHODS@#Between 2013 and 2018, patients with femoral intertrochanteric fractures who were initially treated by intramedullary nail fixation but had difficult reduction using the traction beds were retrospectively reviewed. Decision for an additional surgery was based on the displacement of the fracture. The patients were then divided into two groups: those in the control group received an open reduction surgery while those in the observation group received a closed reduction surgery using a minimally invasive wire introducer to guide the wire that could assist in fracture reduction. The operation time, blood loss, visual analogue scale scores, angulation, reduction, neck-shaft angle, re-displacement, limb length discrepancy, and union time were then recorded and analyzed to determine the efficiency of the wire introducer technique. Categorical variables were analyzed by using Chi-square test, while continuous variables by independent t-test and the Mann-Whitney test accordingly.@*RESULTS@#There were 92 patients included in this study: 61 in the control group and 31 in the observation group. There were no significant differences in baseline demographic factors between the two groups. All surgeries were successful with no deaths within the perioperative period. The average follow-up time for the patients was 23.8 months. However, the observation group had a significantly shorter operation time, lower visual analogue scale score, less intraoperative bleeding, and shorter fracture healing time. There were no significant differences in the angulation, reduction, neck-shaft angle, and limb length discrepancy between the two groups.@*CONCLUSION@#The minimally invasive wire guide achieved a similar effect to that of open reduction in the treatment of intertrochanteric fractures with difficult reduction. Moreover, the minimally invasive wire introducer is a good technology that accurately guides the wire during reduction. Indeed, it is an effective technique and achieves good clinical outcomes in restoration of irreducible femoral intertrochanteric fractures.

Clinical efficacy and technical characteristics of percutaneous endoscopic lumbar discectomy in the treatment of upper lumbar disc herniation / 中国骨伤

OBJECTIVE@#To analyze the clinical efficacy and technical characteristics of percutaneous endoscopic lumbar discecomy in the treatment of upper lumbar disc herniation.@*METHODS@#The clinical data of 9 patients with upper lumbar disc herniation underwent percutaneous endoscopic lumbar discecomy from January 2012 to October 2019 were retrospectively analyzed. There were 6 males and 3 females, aged 26 to 79 years, including 2 patients with L disc herniation and 7 patients with L2, 3 disc herniation. Visual analogue scale (VAS) and Japanese Orthopeadic Association (JOA) score were recorded before and after surgery. The clinical efficacy was evaluated according to the modified Macnab standard.@*RESULTS@#All 9 patients were followedup, and the follow-up time was 1 day and 3 months after surgery. The operation time was 1.5 to 2.9 h and postoperative hospital stay was 5 to 8 d. No cerebrospinal fluid leakage or spinal cord injury occurred during the operation. Preoperative and postoperative at 1 day, 3 months, the VAS scores of 9 patients were 7 to 8 scores, 1 to 3 scores, 0 to 1 case, JOA scores were 5 to 7 scores, 15 to 24 scores, 21 to 26 scores, respectively. The improvement rate of JOA was 36.4% to 78.3% on the first day and 65.2% to 87.5% three months after operation. According to modified Macnab standard to evaluate effect, 4 cases got excellent results, 4 good, 1 fair.@*CONCLUSION@#Percutaneous endoscopic lumbar discecomy has reliable therapeutic effect for upper lumbar disc herniation in line with the indications, and it has the characteristics of small trauma and short operation time, so it is more suitable for middle aged and elderly patients with poor physique and can replace part of transforaminal lumbar interbody fusion.

Effect of Bimin Decoction on Aquaporin 5 in Nasal Mucosa of Allergic Rhinitis Rats with Lung and Spleen Qi Deficiency Syndrome Via NF-κB Signaling Pathway / 中国实验方剂学杂志

Objective::To observe the effect of Bimin decoction(BMD) on nuclear factor-kappa B(NF-κB) signaling pathway and aquaporin 5(AQP5) expression in allergic rhinitis (AR) rats with lung and spleen Qi deficiency syndrome(LSQDS), in order to study the mechanism in treating AR. Method::Fifty-six SD rats were randomly divided into seven groups: control group, AR group, LSQDS AR group, BMD low dose two weeks group and four weeks group, BMD high dose two weeks group and four weeks group. The control group did not intervened, the AR group established the AR disease model with ovalbumin (OVA) as the allergen, the other five groups established the LSDQS model with smoke and senna gavage, and also established the AR disease model with OVA sensitization at the same time as the AR group. After the model was established successfully, four BMD intervention groups were separately given low dose BMD (11.3 g·kg-1) for 2 weeks and 4 weeks, and high dose BMD (22.6 g·kg-1) for 2 weeks and 4 weeks. To observe the general situation of the rats, hematoxylin eosin (HE) staining was used to observe the pathological changes of the nasal mucosa, immunohistochemistry and Western blot were used to detect the expression levels of NF-κB and AQP5, real-time fluorescent quantitative polymerase chain reaction technique (Real-time PCR)was used to detect mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6). Result::The typical AR symptoms were found in AR rats, the AR symptoms and lung and spleen Qi deficiency symptoms were found in AR rats with LSQDS at the same time, and the AR symptoms and lung and spleen Qi deficiency symptoms were significantly improved after the intervention of BMD. Compared with the control group, the typical histopathological changes of nasal mucosa were found in AR group and LSQDS AR group, with a higher behavioral score (P<0.05), and the expression of NF-κB and AQP5 protein increased (P<0.05), the expression of IL-1β, TNF-α, IL-6 and AQP5 mRNA increased (P<0.05). Compared with AR group, the pathological changes of nasal mucosa in LSQDS AR group were more serious, and the expression of NF-κB protein in nucleus increased (P<0.05), the expression of TNF-α and AQP5 mRNA increased (P<0.05). Compared with LSQDS AR group, the pathological changes of nasal mucosa in the groups which interfered by BMD were improved, and the expression of NF-κB and AQP5 protein decreased (P<0.05), the expression of IL-1β, TNF-α, IL-6 and AQP5 mRNA decreased (P<0.05). Compared with BMD low-dose two-week group, the expression of NF-κB protein in nucleus decreased (P<0.05) in BMD high dose four week group. Conclusion::Compared with AR group, the AR condition of the rats with LSQDS is more serious under the same allergen stimulation, BMD can treat AR and reduce the over secretion of glands, which may be related to inhibit the expression of AQP5 by inhibiting the NF-κB signaling pathway.

Establishment of gastric cancer SGC-7901 cell line with stable lncRNA BC002811 silencing / 医学研究生学报

Objective The aim of this study was to construct a recombinant lentivirus-mediated short hairpin RNA (shRNA) expression vector targeting the long non-coding RNA (lncRNA) BC002811 and establish a gastric cancer SGC-7901 cell line with stable BC002811 down-regulation. Methods Three small interfering RNAs (siRNA) were designed and synthesized. The best sequence for RNA interference was selected by real-time quantitative PCR (qPCR) and inserted into the lentiviral vector pLVX-shRNA2. After identification by DNA sequencing, the lentiviral vectors carrying BC002811 shRNA were packaged in HEK293T cells. The lentiviral particles were collected to infect human gastric cancer SGC-7901 cells. After screened by limiting dilution analysis, the SGC-7901 cell line with stable BC002811 down-regulation was established, the expression level of BC002811 detected by qPCR, and the effect of BC002811 on the proliferation of the cells analyzed by MTS. Results The results of qPCR showed that BC002811 siRNA-1 was the most effective siRNA sequence, with a knockdown efficiency of 87%. The recombinant lentiviral vector was packaged in the HEK293T cells with a viral titer of 3.7 × 108 TU/mL in the shRNA-1 group as compared with 4.5 × 108 TU/mL in the control. The expression of BC002811 in the shRNA-1 group was only 10% of that in the control group (P < 0.01), which indicated the successful establishment of the gastric cancer SGC-7901 cell line with stable BC002811 down-regulation. BC002811 knockdown significantly inhibited the proliferation of the SGC-7901 cells in the shRNA-1 group as compared with the control. Conclusion A recombinant lentiviral vector expressing BC002811 shRNA was successfully constructed and the gastric cancer cell line SGC-7901 with stable BC002811 silencing was established.

Xylaroisopimaranin A, a New Isopimarane Derivative from an Endophytic Fungus Xylaralyce sp

Five secondary metabolites, including a new isopimarane derivative xylaroisopimaranin A (1), were isolated from the endophytic fungus Xylaralyce sp. (HM-1), and their structures were elucidated by 1D, 2D NMR, MS and CD spectra. Their bioactivities were performed to antibacterial, Hep G2 cells cytotoxicity and brine shrimp inhibition. The biological evaluation results showed that the xylaroisopimaranin A (1), xylabisboein B (2), griseofulvin (3) , 5-methylmellein (4) and mellein-5-carboxlic acid (5) displayed no significant Hep G2 cells cytotoxicity and antibacterial acitivity, but they inhibited the brine shrimp with IC₅₀ from 0.5 to 25 µmol/mL.

Repositioning drug discovery for Alzheimer's disease based on global marketed drug data / 药学学报

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the life of the elderly and there is no effective therapy to treat or delay the onset of this disease. Due to the multifactorial etiology of this disease, the multi-target-directed ligand (MTDL) approach is an innovative and promising method in search for new drugs against AD. In order to find potential multi-target anti-AD drugs through reposition of current drugs, the database of global drugs on market were mined by an anti-AD multi-target prediction platform established in our laboratory. As a result, inositol nicotinate, cyproheptadine, curcumin, rosiglitazone, demecarium, oxybenzone, agomelatine, codeine, imipramine, dyclonine, melatonin, perospirone, and bufexamac were predicted to act on at least one anti-AD drug target yet act against AD through various mechanisms. The compound-target network was built using the Cytoscape. The prediction was validated by molecular docking between agomelatine and its multiple targets, including ADORA2A, ACHE, BACE1, PTGS2, MAOB, SIGMAR1 and ESR1. Agomelatine was shown to be able to act on all the targets above. In conclusion, the potential drugs for anti-AD therapy in the database for global drugs on market was partially uncovered using machine learning, network pharmacology, and molecular docking methods. This study provides important information for drug reposition in anti-AD therapy.

Relationship between insertion/deletion polymorphism of angiotensin converting enzyme gene and type 2 diabetic kidney disease / 中华检验医学杂志

Objective To explore the interaction of angiotensin converting enzyme (ACE) insertion/deletion(I/D) polymorphism(rs1799752)with diabetic kidney disease (DKD) development as well as its interaction with smoking and obesity in Chinese type 2 diabetic mellitus (T2DM) using the improved experiment method. Methods From June 2016 to March 2018, 300 T2DM patients with DKD [DKD(+)] and 300 T2DM patients without DKD[DKD(-)] were selected from China-Japan Friendship Hospital. The improved Triple Primer Method that combined PCR with capillary electrophoresis was established in this study to detect the ACE genotype. The relevant clinical data as well as the frequencies of genotype and allele of ACE gene I/D polymorphism between two groups were statistically analyzed. Patients were further grouped based on smoking status and obesity for multivariate regression. Results Frequency of the DD genotype and D allele were significantly higher in DKD(+) group than in DKD(-) group [DD genotype:15.0％ (45 cases) vs 7.3％(22 cases),χ2=10.8, P=0.004;D allele:36.5％(219 cases) vs 28.0％(168 cases),χ2=9.92, P=0.02]. Multivariate logistic regression analysis found that D allele of rs1799752 was associated with a significantly higher risk of DKD in both recessive model(OR=1.45, 95％CI:1.06-2.00, P=0.022 after adjustments) and additive model(OR=1.41, 95％CI:1.04-1.90, P=0.025 after adjustments). In the smoker group and the obese group, D allele showed significant relationship with DKD incidence (P<0.05 after adjustments) in both recessive model and dominant model. No such relationships were observed in non-smoker group and non-obese group (P>0.05). Conclusions I/D polymorphism of ACE gene is associated with the incidence of DKD in T2DM patients. DD genotype of the ACE gene is the risk factor for T2DM patients with DKD. D allele may increase DKD incidence in the presence of smoking and obesity.

Spatio-temporal expression of dentin sialophosphoprotein and collagen Ⅰ during molar tooth germ development in vps4b knockout mouse / 华西口腔医学杂志

OBJECTIVE@#To verify the effect of the mutant gene vps4b on the expression of tooth development-related proteins, dentin sialophosphoprotein (DSPP) and collagenⅠ (COL-Ⅰ).@*METHODS@#Paraffin tissue sections of the first molar tooth germ were obtained from the heads of fetal mice at the embryonic stages of 13.5, 14.5, and 16.5 days and from the mandibles of larvae aged 2.5 and 7 days after birth. The immunohistochemical method was used to detect the expression and location of DSPP and COL-Ⅰ in wild-type mouse and vps4b knockout mouse.@*RESULTS@#DSPP and COL-Ⅰ were not found in the bud and cap stages of wild-type mouse molar germ. In the bell stage, DSPP was positively expressed in the inner enamel epithelium and dental papilla, whereas COL-Ⅰ was strongly expressed in the dental papilla and dental follicle. During the secretory and mineralized periods, DSPP and COL-Ⅰ were intensely observed in ameloblasts, odontoblasts, and dental follicles, but COL-Ⅰ was also expressed in the dental papilla. After vps4b gene knockout, DSPP was not expressed in the dental papilla of the bell stage and in the dental papilla and dental follicle of the secretory phase. The expression position of COL-Ⅰ in the bell and mineralization phase was consistent with that in the wild-type mice. Moreover, the expression of COL-Ⅰ in the dental papilla changed in the secretory stage.@*CONCLUSIONS@#Gene vps4b plays a significant role in the development of tooth germ. The expression of DSPP and COL-Ⅰ may be controlled by gene vps4b and regulates the development of tooth dentin and cementum together with vps4b.

Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer's disease / 中国天然药物

Naodesheng (NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease (AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.

Network pharmacology study of Chinese medicine Xiao-Xu-Ming decoction based on vasoconstrictor related GPCR targets / 中国药理学与毒理学杂志

OBJECTIVE Using bioinformatics methods, to establish Xiao-Xu-Ming decoction (XX-MD)"compound-vasoconstriction G Protein-Coupled Receptors(GPCR)targets"network,and analyze the vasoconstriction regulatory effective components and the potential targets of XXMD. METHODS Ac-cording to the XXMD herb sources,we retrieved the chemical structures from the national scientific da-ta sharing platform for population and health pharmaceutical information center,TCMSP database and the latest research literature.The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties.Five kinds of vasoconstriction GPCR crystal structure including 5-HT receptors(5-HT1AR,5-HT1BR),AT1R,β2-AR,hUTR and ETB were retrieved from Bank Pro-tein Data Bank database or homology modeling using Discovery Studio 4.1 built-in modeling tools.After virtual screening by Libdock molecular docking,the highest rated 50 compounds of each target were col-lected and analyzed. The collected data were further used to construct and analyze the network. RE-SULTS 859 single compound structures information in XXMD were generalized following the screen-ing of obtained 2043 compounds.The complicated compound-vasoconstriction GPCR targets network of XXMD was then constructed and analyzed by molecular docking with the above five kinds of GPCR target receptors. Most of the chemical composition effects were associated with different vasoconstric-tion GPCR targets,while a few effective components can be applied to multiple GPCR targets at the same time,therefore forming synergies.CONCLUSION Vasorelaxant effects of XXMD may not only result from the collaborative interaction between a variety of active ingredients in Chinese medicine and multi-ple targets,but also from the interaction between some effective component and multiple targets.

Network mechanism on effective constituents from Polygala Tenuifolia for anti-Alzheimer Disease / 中国药理学与毒理学杂志

OBJECTIVE To clarify out the network pharmacology mechanism of Polygala tenuifolia against Alzheimer disease(AD).METHODS Firstly,we collected the chemical constituents from Polyg-ala tenuifolia and key targets toward AD.Machine learning algorithms were applied to construct classifi-ers for predicting the effective constituents. Secondly, docking models were utilized for further evalua-tion.Finally,we built constituent-target,target-target network and target-biology pathway network.RE-SULTS 104 chemical constituents Polygala tenuifolia from were collected.Through prediction of blood-brain penetration and validation,36 chemical constituents were selected among 100 chemical constitu-ents,their action targets mainly focused on AChE,COX-2,TNF-α,insulin-degrading enzyme and APP. Their main structure types include Polygala saponins, Polygala glycosides, Polygala shrubby ketones, polygala xanthones and sterols,which acted on AchE,APP,M-TAU,GSK3β and 5HT1A with high fre-quency.Gene-Ontology and KEGG enrichment analysis showed that the main pathways of these con-stituents involve in neurotransmitter release,synaptic conduction and synaptic plasticity,apoptosis reg-ulation,phosphorylation pathway,Ca2+signaling pathway,and so on.CONCLUSION This study uncov-ered a network mechanism of Polygala tenuifolia against Alzheimer disease,which may provide impor-tant information for the further study and new drug development.

Network pharmacology-based analysis of Chinese herbal Naodesheng formula for application to Alzheimer's disease / 中国天然药物

Naodesheng (NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease (AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.

Network pharmacology study of Xiaoxuming Decoction based on vasodilatory and vasoconstrictory related GPCR targets / 中国中药杂志

In this study, bioinformatics methods such as molecular docking and network pharmacology were adopted to establish Xiaoxuming Decoction (XXMD) "compound-vasodilatory and vasoconstrictory related G protein-coupled receptors (GPCR) targets" network, then the vascular function regulatory effective components and the potential targets of XXMD were analyzed. Based on the XXMD herb sources, the chemical structures of the compounds were retrieved from the national scientific data sharing platform for population and health pharmaceutical information center, TCMSP database and the latest research literatures. The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties. Then, five kinds of vasodilatory and vasoconstrictory related GPCR crystal structure including 5-HT receptors (5-HT1AR, 5-HT1BR), AT1R, β2-AR, hUTR and ETB were retrieved from RCSB Protein Data Bank database or constructed by homology modeling of Discovery Studio 4.1 built-in modeling tools. After virtual screening by Libdock molecular docking, the highest rated 50 compounds of each target were collected and analyzed. The collected data were further used to construct and analyze the network by Cytoscape 3.4.0. The results showed that most of the chemical composition effects were associated with different vasodilatory and vasoconstrictory related GPCR targets, while a few effective components could be applied to multiple GPCR targets at the same time, therefore forming synergies and vasorelaxant effects of XXMD.

DL0410, a candidate for anti-Alzheimer disease with multiple targets in multiple pathways / 中国药理学与毒理学杂志

OBJECTIVE To find a promising candidate for anti- Alzheimer disease (AD) with multiple targets in multiple pathways. METHODS A series of classifiers were constructed for predicting the active compounds against 51 key targets toward Alzheimer disease (AD) using the multitarget-quantitative structure- activity relationships (mt- QSAR) method. While drug screening assays were established to evaluate the predicted active molecules. In addition, various cellular models and animal models related with AD were set up to further study the effects of the active compounds. RESULTS A system for the discovery of Multitarget-Directed Ligands against AD was set up and applied, the predicted active compounds were validated by the drug screening assays, and several active compounds with multiple targets were discovered. Among them, DL0410 exerted high activity on H3R, α7nAChR, AChE and ERα, also displayed the most significant effect in improving the ability of memory and learning in several AD animal models. The study on its action mechanisms showed that it's effect may partially through increasing neurotransmitter, inhibiting oxidative emergency, inhibiting the expression of APP, and promoting long- term potentiation. Besides, DL0410 is of more safety than the first- line clinical medicines. CONCLUSION DL0410 is a promising candidate for further development for AD treatment.