[Study on anticoagulant material basis and mechanism of Trichosanthis Semen and its shell and kernel based on spectrum-effect relationship integrated molecular docking].

This study explored the anticoagulant material basis and mechanism of Trichosanthis Semen and its shell and kernel based on spectrum-effect relationship-integrated molecular docking. High performance liquid chromatography(HPLC) fingerprints of Trichosanthis Semen and its shell and kernel were established. Prothrombin time(PT) and activated partial thromboplastin time(APTT) in mice in the low-and high-dose(5, 30 g·kg~(-1), respectively) Trichosanthis Semen, the shell, and kernel groups were determined as the coagulation markers. The spectrum-effect relationship and anticoagulant material basis of Trichosanthis Semen and its shell and kernel were analyzed with mean value calculation method of Deng's correlation degree(MATLAB) and the common effective component cluster was obtained. Then the common targets of the component cluster and coagulation were retrieved from TCMSP, Swiss-TargetPrediction, GenCLiP3, GeneCards, and DAVID, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. The main anticoagulant molecular mechanism of the component cluster was verified by SYBYL-X 2.1.1. The spectrum-effect relationship of Trichosanthis Semen and its shell and kernel was in positive correlation with the dosage. The contribution of each component to anticoagulation was not the same, suggesting that the material basis for anticoagulation was different, but they have common effective components(i.e. common material basis), such as adenine(peak 3), uracil(peak 4), hypoxanthine(peak 6), xanthine(peak 9), and adenosine(peak 11). Network pharmacology showed that these components can act on multiple target proteins such as NOS3, KDR, and PTGS2, and exert anticoagulant effect through multiple pathways such as VEGF signaling pathway. They involved the biological functions such as proteolysis, cell component such as cytosol, and molecular functions. The results of molecular docking showed that the binding free energy of these components with NOS3(PDB ID: 1 D0 C), KDR(PDB ID: 5 AMN), and PTGS2(PDB ID: 4 COX) was ≤-5 kJ·mol~(-1), and the docking conformations were stable. Spectrum-effect relationship-integrated molecular docking can be used for the optimization, virtual screening, and verification of complex chemical and biological information of Chinese medicine. Trichosanthis Semen and its shell and kernel have the common material basis for anticoagulation and they exert the anticoagulant through multiple targets and pathways.

TGF-ß isoforms inhibit hepatitis C virus propagation in transforming growth factor beta/SMAD protein signalling pathway dependent and independent manners.

Transforming growth factor beta (TGF-ß) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation-associated responses. However, the antiviral activities and mechanisms of TGF-ß isoforms, including TGF-ß1, TGF-ß2 and TGF-ß3, remain unclear. Here, we demonstrated that all of the three TGF-ß isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-ß isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-ß isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-ß/SMAD signalling pathway-dependent and TGF-ß/SMAD signalling pathway-independent manners. TGF-ß isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-ß1 and TGF-ß2, not TGF-ß3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and α-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-ß isoforms in the HCV-related liver disease progression.

Mutation at a new allele of the dysferlin gene causes Miyoshi myopathy: A case report.

Miyoshi myopathy (MM) is a rare autosomal recessive disorder caused by dysferlin (DYSF) gene mutation. Miyoshi myopathy-inducing mutation sites in the DYSF gene have been discovered worldwide. In the present study, a patient with progressive lower extremity weakness is reported, for which MM was diagnosed according to clinical manifestations, muscle biopsy, and immunohistochemistry. In addition, the DYSF gene of the patient and his parents was sequenced and analyzed and two heterozygous mutations of the DYSF gene (c.4756C> T and c.5316dupC) were discovered. The first mutation correlated with MM while the second was a new mutation. The patient was diagnosed with a compound heterozygous mutation. The mutation site is a new member of pathogenic MM gene mutations.

Santin inhibits influenza A virus replication through regulating MAPKs and NF-κB pathways.

Influenza A virus (IAV) causes high morbidity and significant mortality worldwide. Given the limitations of existing vaccination and antiviral drugs, it is urgent to develop new anti-influenza drugs. Flavonoids are natural polyphenolic compounds with broad applications to treatments for influenza infection. In this study, we demonstrated that santin, a flavonoid compound, showed anti-influenza activity in MDCK and THP-1 cells. Mechanistic studies revealed that santin depressed the phosphorylation of p38 MAPK, JNK/SAPK, ERK, and NF-κB factor and subsequently attenuated the expression of inflammatory cytokines in IAV-infected cells. Thus, santin is a potential candidate for the future development of anti-IAV drugs.

[Anti-platelet aggregation and anti-thrombotic mechanism of Trichosanthis Fructus combined with aspirin based on network pharmacology].

To explore the anti-platelet aggregation and anti-thrombotic mechanisms of Trichosanthis Fructus combined with aspirin based on network pharmacology and the validation of arteriovenous by pass model in rats. The databases of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome(DRAR-CPI),Universal Protein Resource(Uniprot) and the Database for Annotation,Visualization,and Integrated Discovery(DAVID) were used to predict protein targets and analyze biological pathway and signal pathway in the combination of Trichosanthis Fructus with aspirin. The effects of pretreatment with Trichosanthis Fructus pellets,aspirin pellets and their combination on thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α) and cyclic adenosine monophosphate(c AMP) in rat thrombotic model were studied. Through the study of network pharmacology,12 components of aspirin and Trichosanthis Fructus,including hydroxygenkwanin,quercetin and adenosine,were found to show the anti-platelet aggregation and anti-thrombosis mechanisms through9 common protein targets,such as SRC,RAC1,MAPK14,MAPK1,AKT1,and 14 common signaling pathways,such as VEGF signaling pathway. After the intervention with Trichosanthis Fructus pellets combined with aspirin pellets,the vascular endothslia growth factor(VEGF) signaling pathway can be activated to inhibit platelet aggregation and improve vascular endothelial function,and show the anti-platelet aggregation and anti-thrombosis mechanisms,which verify the results of the network pharmacology,and explain the anti-platelet aggregation and anti-thrombotic mechanisms of the combination of Trichosanthis Fructus pellets with aspirin pellets.

[Research progress on chromatographic fingerprint similarity evaluation method for traditional Chinese medicine in the past 30 years（1988-2017）and its prospect].

Over the past 30 years, the chromatographic fingerprint technology of traditional Chinese medicine (TCM) has been developed from academic discussion to application for the research and development of TCM which has promoted the technological innovation of Chinese medicine industry and the progress of quality standard of TCM. The similarity evaluation method of chromatographic fingerprint of TCM has played a key role in this process. According to the number of literature and research tendency in terms of the chromatographic fingerprint in the last 30 years, the chromatographic fingerprint evaluation could be divided into three stages: the direct comparison stage (1988-1999), similarity evaluation stage (2000-2009) and the similarity evaluation development stage (2010-2017). In this paper, the research progress of chromatographic fingerprints similarity evaluation of TCM in the last 30 years and its prospect were discussed, which may lead to a more mature stage for this method.

[Effect of different data standardization methods on spectrum-effect relationship for anticoagulation of Trichosanthis Fructus dropping pills].

To study the effect of different data standardization methods on the spectrum-effect relationship for anticoagulant effect of Trichosanthis Fructus dropping pills. The spectrum-effect relationship was studied by using grey correlation degree method between three doses of Trichosanthis Fructus dropping pills and prothrombintime (PT) in mice. The effect of 10 data standardization methods, namely minimization method, maximum method, data extreme difference method, standard deviation standardization method, initialization transformation method, mean transformation method, ratio of each chromatographic peak area to the total peak area, ratio of each chromatographic peak area to the common peak area, logarithmic standardization method and tangent normalization method on the spectrum-effect relationship between Trichosanthis Fructus dropping pills and PT in mice was evaluated by using relative correlation degree as the index. The results of spectrum-effect relationship can be expressed by the minimization method, the data extreme difference method, the standard deviation standardization method, the initialization method and the mean transformation method, with highest relative correlation degree by the mean transformation method. As compared with the mean transformation method, there were significant differences between the high dose group and the medium dose group in the minimization method and the data extreme difference method (P<0.01), while the minimization method in the low dose group showed statistical significance (P<0.05). The standard deviation standardization method, initialization method and the mean transformation method can be used to study the spectrum-effect relationship for the anticoagulation of Trichosanthis Fructus dropping pills.

[Spectrum-activity relationship of trichosanthis fructus and trichosanthis fructus strip pieces for rat myocardial ischemia-reperfusion injury].

To investigate the spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces for rat myocardial ischemia-reperfusion injury. HPLC fingerprints of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were established, and the values of creatinekinase-MB (CK-MB), myoglobin (MYO) and cardiac troponin-T (cTNT) in 3 dose groups (2.25, 13.5, 27.0 g·kg⁻¹, equivalent to the crude herb g·kg⁻¹) of Trichosanthis Fructus and Trichosanthis Fructus strip pieces with myocardial ischemia-reperfusion injury in rats were measured, and the grey relational analysis was used to study the spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces for rat myocardial ischemia-reperfusion injury. With the dosage increase from 2.25 g·kg⁻¹ to 27.0 g·kg⁻¹, the correlation degree of spectrum-activity relationship of Trichosanthis Fructus and Trichosanthis Fructus strip pieces was also enhanced, but the change trend was different between these two groups. According to the frequency of the top 10 peaks in the correlation degree, peak 17, 14, 16, 19, 32, 12, 26, 30, 4, 6 and 2 were the basic effective substances group of Trichosanthis Fructus, peak 6,14,12,32,30,4 and 6 were the basic effective substances group of Trichosanthis Fructus strip pieces. Peak 6, 14, 12, 32, 30, 4 and 26 in fingerprints of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were the main common pharmacodynamic substance base, among them, peak 6 was 5-hydroxymethyl furfural, peak 14 was vanillic acid and the peak 28 was rutin, but the correlation degree with the efficacy was different. The effect of Trichosanthis Fructus and Trichosanthis Fructus strip pieces on rat myocardial ischemia-reperfusion injury was due to the synergistic effect of the effective substance groups related to the dosage. The essential pharmacodynamic substance groups of Trichosanthis Fructus and Trichosanthis Fructus strip pieces were different, but they shared a common active ingredient group.

Corydaline inhibits enterovirus 71 replication by regulating COX-2 expression.

Enterovirus 71 (EV71) is a huge threat to the worldwide public health and there is no approved antiviral drug for EV71-induced disease therapy. Corydaline exists antiallergic and antinociceptive activities, but the anti-EV71 activity of corydaline is still not reported. In this study, corydaline could suppress the expression of viral structural and non-structural proteins. Furthermore, corydaline inhibits EV71 replication by suppressing the COX-2 expression and the phosphorylation of JNK MAPK and P38 MAPK but not ERK MAPK in vitro. Based on these findings, corydaline could be a potential lead or supplement for the development of new anti-EV71 agents in the future.

[Pharmacodynamics Study on Gualou Xiebai Dropping Pills and Its Medicinal Ingredients in Prescription].

OBJECTIVE: To study the pharmacodynamics of Gualou Xiebai Dropping Pills and its medicinal ingredients in prescription on anti-myocardial ischemia. METHODS: SPF Rats were divided randomly into eleven groups with ten rats in each group and half male and half female, the rats were respectively given the physiological saline(blank group and model group), Gualou, Xiebai, Gualou Xiebai Baijiutang (all equivalent to the crude herb of 22. 5 g/kg), Gualou Xiebai. Dropping Pills in the doses of 3. 75,11. 25,22. 5,33. 75 and 45 g/kg and Compound Danshen Drop Pills of 0. 085 g/kg by gavage one time a day for seven days. Except blank group, other rats were given by intraperitoneal injection of isoproterenol to establish myocardial ischemia models, changes of ST segments in ECG were observed in all groups, and the levels of SOD, NO, HDL-C, MDA, CAT, LDH and CK in blood plasma were detected, and the pathological changes of myocardial tissues were observed under light microscope by HE staining. RESULTS: Compared with model group, ST segments in ECG dropped markedly at different time point which included 10,11 and 12 (P <0. 05) in Gualou Xiebai Drop Pills groups of 22. 5, 33. 75 and 45 g/kg, time points were more than those of other groups. Gualou Xiebai Dropping Pills groups of 22. 5 and 33. 75 g/kg improved the levels of SOD, MDA, CAT, NO, HDL-C, LDH and CK in blood plasma in model rats significantly (P <0. 01 or P <0. 05). Gualou Xeibai Dropping Pills improved the pathological changes of myocardial tissues at all dosages. CONCLUSION: Gualou Xiebai Drop Pills can effectively restrain the acute myocardial ischemia induced by isoproterenol in rats, compared with Gualou, Xiebai or Gualou Xiebai Baijiutang, Gualou Xiebai Drop Pills obtains a favourable effect.

[Study on HPLC Fingerprint of Trichosanthes Fruit and Its Processed Products].

OBJECTIVE: To study the correlation on chemical fingerprint features between Trichosanthis Fructus and its processed products. METHODS: The chemical fingerprints were established by HPLC for the ethyl acetate extraction and the n-butanol extraction in Trichosanthis Fructus and its processed products,the common pattern was established by the mean and the median, and the similarity degree between Trichosanthis Fructus and its processed products was calculated by the correlation coefficient method and the included angle cosine method. RESULTS: There were 24 common peaks in the fingerprints of ethyl acetate extraction of Trichosanthis Fructus and its processed products,the average similarity degree was calculated separately by the correlation coefficient method and the included angle cosine method:the former as the value was 0. 8497(mean), 0. 8344(median); and the latter as the value was 0. 8429(mean), 0. 8536 (median); there were 6 common peaks in the fingeprints of n-butanol extraction of Trichosanthis Fructus and its processed products, the average similarity degree was calculated by the correlation coefficient method and the included angle cosine method:the former as the value was 0. 9044 (mean), 0. 9076 (median); and the latter as the value was 0. 9075 (mean), 0. 9081 (median). CONCLUSION: Main peaks have good correlation between Trichosanthis Fructus and its processed products. This method can provide theoretical basis for processing and quality control of Trichosanthis Fructus.

[Spectrum-Effect Relationship of GualouXiebai Dropping Pills on Myocardial Ischemia].

OBJECTIVE: To study the relationship between HPLC characteristic spectrum and pharmacodynamics on anti-myocardial ischemia of GualouXiebai dropping pills. METHODS: HPLC characteristic spectrum of GualouXiebai dropping pills was established, dropping pills were divided into five dose groups (3.75, 11.25, 22.5, 33.75 and 45 g/kg, equivalent to the crude herb g/kg), the mice were orally administered dropping pills once daily for 7 d, 90 min after the mice were given by intraperitoneal injection of isoprenaline to establish myocardial ischemia models, the level of CK in blood plasma were detected; Then, the correlation between characteristic spectrum and biochemical index CK was studied by grey relational analysis method. RESULTS: The correlation between each common peak and CK had gradually increased with the dose increased from 3.73 g/kg to 33.75 g/kg, but when the dose reached to 45 g/kg, the correlation between each common peak and CK had decreased. The variation trends of correlation of spectrum-effect relationship for different dose were similar,but the correlation variation trend of the efficacy on the No. 8 peak in 33.75 g/kg group with the other four groups in the opposite, the change trends of the No. 11 peak in 22.5 g/kg group, the No. 24 peak in 33. 75 g/kg group and the No. 37 peak in 45 g/ kg group with 3.75 g/kg group and 11.25 g/kg group on the contrary. The relational orders of spectrum-effect relationship were not consistent, respectively( the first 15 peaks) :11 > 37 > 24 > 30 > 8 > 21 > 2 > 16 > 1 > 3 > 20 > 15 > 12 > 19 > 7;11 > 37 > 30 > 8 > 21 > 24 > 2 > 1 > 16 > 3 > 27 > 12 > 22 > 20 >10; 8 > 30 > 1 > 2 > 21 > 27 > 31 > 22 > 16 > 12 > 3 > 10 > 9 > 20 > 4; 1 > 2 > 27 > 21 > 31 > 22 > 12 > 16 > 9 > 3 > 10 > 4 > 17 > 30 > 20; 8 > 30 > 1 > 2 > 2 > 2 > 7 > 31 > 22 > 16 > 12 > 3 > 9 > 10 > 20 > 17. CONCLUSION: Anti-myocardial ischemia effect of GualouXiebai dropping pills comes from the synergistic or antagonistic effect among various active ingredients related to the dose. With the difference of the dosage, the relational orders of chemical components to play the role is not the same, but the main components to play a pharmacodynamic of five dose groups are consistent,the existence of the component groups lay a foundation for further study of GualouXiebai dropping pills.

[Influence of the Compatibility of Gualou and Xiebai on Pharmacokinetics of Quercetin in Gualou].

OBJECTIVE: To determine the concentration of quercetin in mouse plasma by HPLC-DAD in different time after oral administration with Gualou Xiebai decoction and Gualou decoction, and to explore the influence of the compatibility of Gualou and Xiebai on pharmacokinetics of quercetin in Gualou. METHODS: The plasma sample was simply deproteinized with acetonitrile, extracted three times by aceticether, evaporated to dryness with a gentle N2 stream, dissolved with methanol and determined by HPLC. The pharmacokinetic parameters were separately calculated and compared with data processing software DAS 2. 0 and SPSS 11. 5 software. RESULTS: After oral administration with Gualou Xiebai decoction and Gualou decoction, the pharmacokinetics of quercetin in mouse plasma accorded with the two-compartment model, and t1/2α, t1/2ß, AUC0-t, AUC0-∞, Cmax, tmax, Ka, K10, K12, K21, CL/F and V1/F all had significant differences(P <0. 05 or P <0. 01). CONCLUSION: Xiebai in Gualou Xiebai decoction has a remarkable effect on pharmacokinetic character of quercetin in Gualou, it can promote the absorption and distribution and reduce the elimination of quercetin, in vivo, as well as increase the bioavailability of quercetin.

Bare-metal stent versus drug-eluting stent in large coronary arteries: meta-analysis of randomized controlled trials.

BACKGROUND: Uncertainties exist with regard to the efficacy of drug-eluting stent (DES) versus bare-metal stent (BMS) in large coronary arteries. OBJECTIVE AND METHODS: The aim of this study was to investigate the efficacy of BMS versus DES in terms of clinical events in large coronary vessels (≥3.0 mm) by performing a meta-analysis of all relevant randomized controlled trials (RCTs). RESULTS: Six RCTs with 4,399 patients were included in this study. Overall, there were no significant between-group differences in the risks of the composite of cardiac death and nonfatal myocardial infarction (cardiac death/MI), cardiac death, myocardial infarction, and stent thrombosis, however, DES was associated with significant reduction in the risk of target vessel revascularization (TVR) compared with BMS [0.48 (0.33, 0.70)] with consistent benefits among patients with reference vessel diameter ≥ 3.5 mm, reference vessel diameter ≥ 4.0 mm, stent length ≤ 15 mm, first-generation DES or second-generation DES. In patients with ≥ 3-year follow-up, there were no significant between-group differences in the risk of cardiac death/MI, TVR, cardiac death, myocardial infarction or stent thrombosis. CONCLUSIONS: This meta-analysis suggests that DES is superior to BMS in terms of adverse cardiac events in large coronary arteries at the mid-term follow-up. The long-term efficacy of newer-generation DES versus BMS in larger coronary arteries is still worth further evaluation.

PML Suppresses Influenza Virus Replication by Promoting FBXW7 Expression.

Influenza A viruses (IAV) are responsible for seasonal flu epidemics, which can lead to high morbidity and mortality each year. Like other viruses, influenza virus can hijack host cellular machinery for its replication. Host cells have evolved diverse cellular defense to resist the invasion of viruses. As the main components of promyelocytic leukemia protein nuclear bodies (PML-NBs), PML can inhibit the replication of many medically important viruses including IAV. However, the mechanism of PML against IAV is unclear. In the present study, we found PML was induced in response to IAV infection and ectopic expression of PML could inhibit IAV replication, whereas knockdown of endogenous PML expression could enhance IAV replication. Further studies showed that PML increased the expression of FBXW7 by inhibiting its K48-linked ubiquitination and enhanced the interaction between FBXW7 and SHP2, which negatively regulated IAV replication during infection. Moreover, PML stabilized RIG-I to promote the production of type I IFN. Collectively, these data indicated that PML inhibited IAV replication by enhancing FBXW7 expression in the antiviral immunity against influenza virus and extended the mechanism of PML in antiviral immunity.

LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network.

Rationale: The forkhead box A1 (FOXA1) is a crucial transcription factor in initiation and development of breast, lung and prostate cancer. Previous studies about the FOXA1 transcriptional network were mainly focused on protein-coding genes. Its regulatory network of long non-coding RNAs (lncRNAs) and their role in FOXA1 oncogenic activity remains unknown. Methods: The Cancer Genome Atlas (TCGA) data, RNA-seq and ChIP-seq data were used to analyze FOXA1 regulated lncRNAs. RT-qPCR was used to detect the expression of DSCAM-AS1, RT-qPCR and Western blotting were used to determine the expression of FOXA1, estrogen receptor α (ERα) and Y box binding protein 1 (YBX1). RNA pull-down and RIP-qPCR were employed to investigate the interaction between DSCAM-AS1 and YBX1. The effect of DSCAM-AS1 on malignant phenotypes was examined through in vitro and in vivo assays. Results: In this study, we conducted a global analysis of FOXA1 regulated lncRNAs. For detailed analysis, we chose lncRNA DSCAM-AS1, which is specifically expressed in lung adenocarcinoma, breast and prostate cancer. The expression level of DSCAM-AS1 is regulated by two super-enhancers (SEs) driven by FOXA1. High expression levels of DSCAM-AS1 was associated with poor prognosis. Knockout experiments showed DSCAM-AS1 was essential for the growth of xenograft tumors. Moreover, we demonstrated DSCAM-AS1 can regulate the expression of the master transcriptional factor FOXA1. In breast cancer, DSCAM-AS1 was also found to regulate ERα. Mechanistically, DSCAM-AS1 interacts with YBX1 and influences the recruitment of YBX1 in the promoter regions of FOXA1 and ERα. Conclusion: Our study demonstrated that lncRNA DSCAM-AS1 was transcriptionally activated by super-enhancers driven by FOXA1 and exhibited lineage-specific expression pattern. DSCAM-AS1 can promote cancer progression by interacting with YBX1 and regulating expression of FOXA1 and ERα.

Effects of extracts from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on MSU crystal-induced rats gouty arthritis.

The effects of extract of Paederia scandens (LOUR.) MERRILL (Rubiaceae) (EPS), a Chinese traditional herbal medicine, on inflammatory and immune responses and their mechanisms in MSU crystals-induced (GA) rats were studied. GA rats were established. Ankle joint volume of rats was measured by volume meter; the level of TNF-alpha and IL-1beta was determined by radioimmunoassay. mRNA expressions of TNF-alpha and IL-1beta in synovial tissue of GA rats were analyzed by RT-PCR, and the expression of NF-kappaB was detected by immunohistochemistry. The administration of EPS (2.25, 4.5 g/kg, ig 9 days) inhibited the inflammatory response in GA rats. The mRNA expressions of TNF-alpha and IL-1beta were also significantly suppressed in synovial tissue. In addition, EPS (2.25, 4.5 g/kg, ig 9 days) inhibited the expression of TNF-alpha and IL-1beta and the biological activity of NF-kappaB. These results suggested that EPS possesses antiinflammatory effects by modulating pro-inflammatory mediators' production in synovial tissue and inactivating NF-kappaB pathway transmembrane signal transduction which plays a crucial role in the pathogenesis of this disease.

Assessment of cerebral infarction after transient cerebral ischemic attack by ABCD2 score combined with the position of intracranial vascular stenosis.

This study aims to investigate the value of the ABCD score combined with the position of the offending vessel stenosis in predicting the risk of transient ischemic attack (TIA) to develop into cerebral infarction.The ABCD score and head magnetic resonance imaging + magnetic resonance angiography (MRA) results of 192 patients with TIA were retrospectively analyzed. With the 7th day as the endpoint time, these patients were divided into 3 groups, according to ABCD scores: low-risk group (n = 105), moderate-risk group (n = 60), and high-risk group (n = 27). Blood vessels were screened using head MRA results, and patients were accordingly divided into 2 groups: proximal vascular stenosis group (n = 71) and nonproximal vascular stenosis group (n = 171). Then, the association of the position of the intracranial vascular stenosis and ABCD score with short-term prognosis was analyzed.Based on the ABCD score, the incidence of cerebral infarction after 1 week was significantly higher in the high-risk group (85.7%) than in the moderate-risk group (16.7%) and low-risk group (1.9%), and the differences were statistically significant (P < .05). When the ABCD score was ≥4 points, the incidence of cerebral infarction after 1 week was significantly higher in the proximal vascular stenosis group (59.1%) than in the nonproximal vascular stenosis group (30.8%), and the difference was statistically significant (P < .05). When the ABCD score was <4 points, the incidence of cerebral infarction after 1 week in the proximal stenosis group (2%) was not significantly different from that in the nonproximal stenosis group (1.9%, P > .05).The ABCD score combined with proximal offending vessel stenosis can improve the short-term prediction of cerebral infarction in patients with TIA.

The angiotensin-converting enzyme (ACE) gene family of Bombyx mori.

We previously reported regarding an ecdysone-inducible angiotensin-converting enzyme (ACE) gene. We found another four ACE genes in the Bombyx genome. The present study was undertaken to clarify the evolutionally changed function of the ACE of Bombyx mori. Core regions of deduced amino acid sequences of ACE genes were compared with those of other insect ACE genes. Five Bombyx genes have the conserved Zn2+-binding-site motif (HEXXH); however, BmAcer4 has only one and BmAcer3 has no catalytic ligand. BmAcer1 and BmAcer2 were expressed in several organs. BmAcer3 was expressed in testes, and BmAcer4 and BmAcer5 were expressed in compound eyes; however, the transcription levels of these three genes were very low. Quantitative RT-PCR and Western analysis were conducted to determine the tissue distribution and developmental expression of BmAcer1and BmAcer2. Transcripts of BmAcer1 and BmAcer2 were found in the reproductive organs during the larval and pupal stages. BmAcer1 was dominant in fat bodies during the feeding stage and showed high expression in the epidermis, wing discs, and pupal wing tissues after the wandering stage. Its expression patterns in epidermis, wing discs, and wing tissues resembled the hemolymph ecdysteroid titer in the larval and pupal stages. Acer1 was observed in the hemolymph at all stages, appearing to be the source of it are fat bodies, wings, and epidermis, and functioning after being secreted into the hemolymph. BmAcer2 was abundant in the midgut during the feeding stage and after the wandering stage and in silk glands after the pupal stage. We conclude that the evolution of BmAcer occurred through duplication, and, thereafter, functional diversification developed.

Genome-wide study of ER-regulated lncRNAs shows AP000439.3 may function as a key regulator of cell cycle in breast cancer.

Estrogen receptor (ER) plays important roles in cell growth, development and tumorigenesis. Although ER-regulated genes have been extensively investigated, little is known about roles of ER-regulated lncRNAs in breast cancer. Here, we conducted genome-wide study of ER-regulated lncRNAs by using RNA-seq, ChIP-seq and TCGA data. A total of identified 114 ER-regulated lncRNAs were identified, many of them were overexpressed in ER+ breast cancer and co-expressed with some key regulators. Silencing one of most prominent lncRNA, AP000439.3, resulted in inhibition of cell cycle progression and proliferation. Further study revealed AP000439.3 can regulate expression of CCND1 through enhancing estrogen receptor induction of CCND1. This finding revealed lncRNAs may serve as important effectors of ER in regulation of gene expression and cell phenotype in breast cancer.