ABSTRACT
Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.
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Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.
ABSTRACT
A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or / studies, the other is for identifying lead compounds against potential drug targets docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 Å on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easy to be updated, and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php). Currently, the webserver contains 42 proteins [20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release] with 69 different conformations/structures and 557 potential ligand-binding pockets in total. With 6 examples, we demonstrated that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.
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Objective To analyze and verify the expression profiles of long non-coding RNAs (lncRNAs) in gastric cancer (GC) metastatic lymphonodus.Methods Microarray analysis was performed in 3 GC positive lymphonodus and 1 normal lymph node with Agilent Array platform to measure the expression levels of lncRNAs and mRNAs and to investigate the expression differences of lncRNAs in GC metastatic lymphonodus and normal lymphonodus, and hierarchical clustering used to screen out the differently expressed lncRNAs.15 up-regulated lncRNAs and 15 down-regulated lncRNAs were randomly chosen and RT-PCR was used to verify the expression differences.Results Comparing with normal lymphonodus, 353 lncRNAs and 547 mRNAs are up-regulated, but 464 lncRNAs and 562 mRNAs are down-regulated in GC metastatic lymphanodus as 6 times or more variation was found.The expressions of lncRNA OR3A4, LOC84740, FCGR1C and C21orf 96 were increased in GC metastatic lymphonodus, but lncRNA MSTO2P, LOC344595, TUG1, TYW3 and KRT8P10 decreased.Conclusions LncRNAs are aberrantly expressed in GC metastatic lymphonodus.
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ObjectiveTo detect methylation status of the 5'CpG island locating in the promoter region of p27 gene in gastric carcinoma and to analyze the relationship between the aberrant methylaion of p27 gene and the bionomics of gastric carcinoma.MethodsMethylation-specific PCR were used to detect the methylation status of p27 in gastric carcinoma( n =49), adjacent tissue of carcinoma ( n =20) and normal tissue(n =10), respectively.ResultsThe mathylation rate is 49％ (24/49) for gastria cancer, 25％(5/20) for tumor-sideward mucosa and 0 (0/10)for normal mucosa.There was a significant positive correlation between gastric carcinoma specimens and normal mucosa specimens ( P ＜ 0. 05 ). There was no significant diference between normal gastric group and tumor-sideward mucosa group ( P ＞ 0. 05 ) and no significant diference between tumor-sideward mucosa group and tumor group ( P ＞ 0. 05 ). The mathylation rate of p27 gene with lymph node metastases (61％) are higher than those without metastasis (28％) (P ＜ 0. 05). And there is no relation on patients' age, sex, tumor size and location.Conclusionp27 gene methylation of the p27 gene is correlated to oncogenesis and metastasis of gastric carcinoma and could lead to the loss of p27mRNA transcription.
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Objective To investigate the expression of EphrinB2 and microvessel density(MVD) in colorectal carcinoma and to analyze the relationship between the expression of EphrinB2 and the biological characteristics of colorectal carcinoma. Methods EphrinB2 and MVD of 63 colorectal carcinoma diagnosed by pathology were examined by immunohistochemistry, and 25 specimens from normal colorectal tissue were examined as controls. Results The expression of EphrinB2 protein was 82.0 % (51/63) in colorectal carcinoma and 32.0 % (8/25) in the normal colorectal tissues, the difference was significant (P <0.05). Meanwhile, MVD was significantly higher in EphrinB2 positive group (39.39±8.97) than that in negative group (33.00 ±10.19) (P<0.05). The expression of EphrinB2 protein had significant positive correlation with differentiation grade, infiltration, lymph node metastases and clinical stage (P <0.05), and had no relation to age, sex, tumor size and location(P >0.05). Conclusion The EphrinB2 protein expression increase may be involved in development of colorectal carcinoma and play important roles in the tumorigenesis and progression of colorectal carcinoma.
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Objective To examine the frequency and mode of distal spread of low and middle rectal cancer in the mesorectum and rectal wall. Methods Thirty-four specimens from low and middle rectal cancer were collected between August 2004 and December 2005 in Cancer Center of Sun Yat-sen University. Twenty-eight specimens of low and middle rectal cancer were collected between October 2006 and October 2007 in Shandong Provincial Hospital of Shandong University. All 62 specimens were studied using large slices stained with CK20. Logistic regression was used to analyze clinicopathologic factors related to distal spread of low and middle rectal cancer in the mesorectum and rectal wall. Results Two types of distal spread of the tumor were observed in rectal wall: submucosa invasion and muscularis propria invasion. Distal spread in rectal wall was observed in 16% (10/62) of the patients. The length of distal spread in rectal wall was found from O. 5 cm to 1.0 cm. Four types of distal spread of the tumor were observed in mesorectum: lymph node invasion, blood and lymphatic vessel invasion, perineural invasion, isolated neoplastic microfoci. Distal spread in mesorectum was observed in 24% (15/62) of the patients. The length of distal spread in mesorectum was found from 0. 5 cm to 4. 0 cm. Three more cases with microcapillary invasion in distal mesorectum was observed by immunohistochemical technique, which was difficult to identify by conventional HE staining. Univariate analysis showed that serum CEA , lymph node invasion, CMI and TNM stage were correlated with distal spread of low and middle rectal cancer in the mesorectum and rectal wall. TNM stage was shown to be independent impact factor by multivariate analysis( Wald = 9. 567, P =0. 002). Conclusion TNM stage is an independent impact factor for distal spread of low and middle rectal cancer in the mesorectum and rectal wall. Resection of 1.5 cm for distal rectal wall is necessary for a curative intention, but it must be emphasized that the clearance for distal mesorectum should be 5 cm at least.
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Objective To explore the relationship between the abnormal expression of anti-oncogene PTEN in gastric carcinoma and the clinicopathological characteristics. Methods Mythylation specific PCR was applied to detect the expression of PTEN methylation in gastric carcinoma and their normal tissues from 45 patients. Results The methylation took place in 40.0 percent in gastric carcinoma and 2.2 percent in their normal tissues, and the difference was significant(P<0.05). The methylation rate in poorly differentiated adenocarcinoma was 60.0 percent ,while 15.0 percent in highly-moderately differentiated group, the difference was significant (P<0.05). In the 24 cases with lymph node metastasis, mythylation was observed in 13 cases, and the difference was significant (P<0.05). Conclusion The methylation of PTEN gene was associated with gastric carcinoma, it may play an important role in the development of the disease.
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A porous hydroxylapatite-containing titania film was prepared by an electrochemical oxidation method, i.e. micro-arc oxidation (MAO). During the oxidation treatment, the titanium sample was immersed in electrolytic solution containing calcium acetate monohydrate and sodium biphosphate dihydrate by using a pulse power supply. The thickness, phase, composition and morphology of the oxide coating were monitored with X-ray diffraction (XRD) and scanning electron microscopy (SEM) with energy dispersive X-ray spectrometer (EDS). The thickness of the MAO film is about 20 microm and the coating where each porous size is no more than 5 microm was porous and uneven, without apparent interface to the titanium substrates. The coating formed in the Ca- and P-containing solution with MAO contained Ca and P along with Ti and O. The Ca/P ratio on the surface is 1.63, while that in the interface is 0.51. XRD showed that the porous coating was made up of anatase, rutile and hydroxyapatite. Such MAO films are expected to have significant medical applications as dental implants and artificial bone joints.