Inokosterone Is A Potential Drug Target of Estrogen Receptor 1 in Rheumatoid Arthritis Patients: Analysis from Active Ingredient of Cyathula Officinalis.

OBJECTIVE: To elucidate the active compounds and the molecular mechanism of Cyathula Officinalis as a drug treatment for rheumatoid arthritis (RA). METHODS: The target genes of active ingredients from Cyathula Officinalis were obtained from bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine. The protein-protein interaction between the target genes were analyzed using STRING and Genemania. The transcriptome of RA patients compared to healthy people (GSE121894) were analyzed using R program package Limma. The relative expression of the target genes was obtained from the RNA-seq datasets. The molecular docking analyses were processed based on the molecular model of estrogen receptor 1 (ESR1) binding with estradiol (PDB ID:1A52). The binding details were analyzed by SYBYL. RESULTS: Inokosterone, ecdysterone, and cyaterone were the 3 active ingredients from Cyathula Officinalis that bind to target genes. Of all the significantly changed genes from RA patients, ESR1, ADORA1, and ANXA1 were significantly increased in mRNA samples of RA patients. CONCLUSION: ESR1, the transcription factor that binds inokosterone in the molecular binding analysis, is the target protein of Cyathula Officinalis.

A combination of four effective components derived from Sheng-mai san attenuates hydrogen peroxide-induced injury in PC12 cells through inhibiting Akt and MAPK signaling pathways.

The present study was designed to investigate whether a combination of four effective components derived from Sheng-mai san (SMXZF; ginsenoside Rb1: ginsenoside Rg1: DT-13: Schizandrol A as 6 : 9 : 4 : 5) could attenuate hydrogen peroxide (H2O2)-induced injury in PC12 cells, focusing on the Akt and MAPK pathways . The PC12 cells were exposed to H2O2 (400 µmol·L(-1)) for 1 h in the presence or absence of SMXZF pre-treatment for 24 h. Cell viability was measured by MTT assay. The efflux of lactate dehydrogenase (LDH), the intracellular content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), and caspase-3 were also determined. Cell apoptosis was measured by Hoechst 33342 staining and Annexin V-FITC/PI staining method. The expression of Bcl-2, Bax, cleaved caspase-3, Akt, and MAPKs were detected by Western blotting analyses. SMXZF pretreatment significantly increased the cell viability and SOD activity and improved the cell morphological changes, while reduced the levels of LDH and MDA at the concentrations of 0.1, 1 and 10 µg·mL(-1). SMXZF also inhibited H2O2-induced apoptosis in PC12 cells. Moreover, SMXZF reduced the activity of caspase-3, up-regulated the protein ratio of Bcl-2 and Bax and inhibited the expression of cleaved caspase-3, p-Akt, p-p38, p-JNK and p-ERK1/2 in H2O2-induced PC12 cells. Co-incubation of Akt inhibitor or p38 inhibitor partly attenuated the protection of SMXZF against H2O2-injured PC12 cells. In conclusion, our findings suggested that SMXZF attenuated H2O2-induced injury in PC12 cells by inhibiting Akt and MAPKs signaling pathways, which might shed insights on its neuroprotective mechanism.

Network pharmacology-based prediction and verification of the molecular targets and pathways for schisandrin against cerebrovascular disease.

AIM: To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification. METHOD: A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting. RESULTS: Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting. CONCLUSION: The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.

Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis.

The previous published data on the association between the 8-oxo-guanine glycosylase-1 (OGG1) and apurinic/apyrimidinic-endonuclease-1 (APEX1/APE1) polymorphisms and lung cancer risk remained controversial. Several polymorphisms in the OGG1 and APEX1 gene have been described, including the commonly occurring Ser326Cys in OGG1 and Asp148Glu in APEX1. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. A total of 37 studies were identified to the meta-analysis, including 9,203 cases and 10,994 controls for OGG1 Ser326Cys (from 25 studies) and 3,491 cases and 4,708 controls for APEX1 Asp148Glu (from 12 studies). When all the eligible studies were pooled into the meta-analysis of OGG1 Ser326Cys polymorphism, significantly increased lung cancer risk was observed in recessive model (OR = 1.17, 95 % CI = 1.03-1.33) and in additive model (OR = 1.21, 95 % CI = 1.03-1.42). In the stratified analysis, significantly increased risk of lung cancer was also observed on the population-based studies (recessive model: OR = 1.26, 95 % CI = 1.08-1.46, additive model: OR = 1.42, 95 % CI = 1.06-1.73) and non-smokers (dominant model: OR = 1.20, 95 % CI = 1.02-1.42, recessive model: OR = 1.20, 95 % CI = 1.02-1.40, additive model: OR = 1.35, 95 % CI = 1.08-1.68). Additionally, when one study was deleted in the sensitive analysis, the results of OGG1 Ser326Cys were changed in Asians (recessive model: OR = 1.16, 95 % CI = 1.06-1.27, additive model: OR = 1.23, 95 % CI = 1.09-1.38). When all the eligible studies were pooled into the meta-analysis of APEX1 Asp148Glu polymorphism, there was no evidence of significant association between lung cancer risk and APEX1 Asp148Glu polymorphism in any genetic model. In the stratified analysis, significantly decreased lung adenocarcinoma risk was observed in recessive model (OR = 0.68, 95 % CI = 0.48-0.97, P (h) = 0.475, I(2) = 0.0 %). Additionally, when one study was deleted in the sensitive analysis, the results of APEX1 Asp148Glu were changed in Asians (recessive model: OR = 1.21, 95 % CI = 1.03-1.43) and smokers (dominant model: OR = 1.62, 95 % CI = 1.08-2.44, additive model: OR = 1.37, 95 % CI = 1.02-1.84). In summary, this meta-analysis indicates that OGG1 Ser326Cys show an increased lung cancer risk in Asians and non-smokers, APEX1 Asp148Glu polymorphism may be associated with decreased lung adenocarcinoma risk, and APEX1 Asp148Glu polymorphism show an increased lung cancer risk in Asians and smokers. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk.

Association between the COMT Val158Met polymorphism and breast cancer risk: a meta-analysis of 30,199 cases and 38,922 controls.

Many studies have reported the role of COMT Val158Met with breast cancer risk, but the results remained controversial. In addition, previous meta-analysis on COMT Val158Met showed conflicting results. Hence, we performed a meta-analysis to investigate the association between breast cancer and COMT Val158Met (30,199 cases and 38,922 controls) in different inheritance models. When all the eligible studies were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and COMT Val158Met polymorphism in any genetic model (dominant model: odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94-1.04, P value of heterogeneity test [P(h)] = 0.009, I(2) = 36.9%; recessive model: OR = 0.97, 95% CI = 0.92-1.02, P(h) = 0.044, I(2) = 28.6%; additive model: OR = 0.98, 95% CI = 0.91-1.05, P(h) = 0.004, I(2) = 40.4%). However, significant between-study heterogeneity was detected in any genetic model. Hence, we performed the stratified analysis according to ethnicity, source of controls, menopausal status, and family history. In the stratified analysis by ethnicity significantly decreased breast cancer risk was observed in Caucasian population (recessive model: OR = 0.96, 95% CI = 0.92-1.00, P(h) = 0.419, I(2) = 3.1%). In conclusion, this meta-analysis indicates that COMT Val158Met polymorphism may be associated with decreased breast cancer risk in Caucasian population. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on COMT Val158Met polymorphisms and breast cancer risk.

[A method for determination of volatile organic compounds in drinking water by purge and trap in combination with gas chromatograph/mass spectrometry].

OBJECTIVE: To establish a method of purge and trap in combination with gas chromatograph/mass spectrometry(P and T-GC/MS) for the rapid determination of minimum multi-mixture of volatile organic compounds (VOCs) in drinking water simultaneously. METHODS: The experimental conditions of P and T, such as desorption temperature, desorption time, the type of the trap and the analytical conditions of GC were optimized. 54 VOCs in drinking water were determined by P and T-GC/MS. RESULTS: The method enjoyed a wide linear range and good precision, the method detection limit(MDL) was 0.01 - 0.5 microg/L, the average recoveries of the method was 90% - 110% and the relative standard deviation (RSD) was 1.24%-7.79%. CONCLUSION: The results showed that the method was accurate and high sensitivity and might be good for application and suitable for trace analysis of VOCs in drinking water.

[Luminescence properties of rare earth ions in 2SrO.0.84 P2O5.0.16 B2O3: RE3+ (RE=Ce, Tb)].

The phosphors of 2SrO.0.84 P2O5.0.16 B2O3: RE3+ (RE=Ce, Tb) were synthesized by high temperature solid state reaction. The luminescence properties of Ce3+, Tb3+ and the sensitization of Ce3+ to Tb3+ were studied. In the excitation spectrum of Ce3+, there are two broad bands at 232 and 296 nm respectively. Because of the large overlap between the emission bands, the authors could not separate them from each other. The authors could get two bands at 325 and 344 nm with the Gaussian fitting method. The possible reason is that these two peaks are from two light centers. In the phosphor of 2SrO.0.84 P2O5.0.16 B2O3: Tb3+, the excitation spectrum of Tb3+ exhibits high absorption at 370 nm and emission spectrum shows the strongest emission peak at 548 nm. The emission from the levels of (5)D3 and (5)D4 of Tb3+ appear at the same time, indicating that non-radiative process between them is inefficient. In the phosphor of Ce3+ and Tb3+ co-doped 2SrO.0.84 P2.O5.0.16 B2O3, efficient energy transfer exists.

[VUV spectral properties of (Y, Gd) Al3 (BO3)4: Tb].

(Y, Gd)A13 (BO3)4 doped with Ce and Tb were prepared by solid state reaction. The structure, VUV excitation properties, excitation were studied. (Y,Gd)Al3 (BO3)4 belongs to trigonal crystal system with thespace group of R32, and the crystal structure does not change as Tb3+ and Ce3+ ions are doped to the crystal lattice. The host absorption band of (Y,Gd)Al3 (BO3)4:Tb moves to longer wavelength as Gd3+ mol concentration increases. The energy transfer between Gd3+ and Tb3+ is very effective, and the samples with high Gd3+ mol concentrations have high radiant efficiencies. It was found that the luminescence of Tb3+ is quenched by Ce3+ in (Y,Gd)Al3(BO3)4:Ce, Tb under VUV excitation.

[Luminescence properties and spectral analysis of long phosphorescent phosphors: Ba(1 - x) Ca (x) Al2O4 : Eu2+, RE3+].

New long phosphorescent phosphors Ba(1 -x),Ca(x)Al2O4 : Eu2+, RE3+ (RE3+ = Dy3+, Nd3+) with tunable color emission have been prepared by solid state reaction. The luminescence properties of the samples are discussed and analyzed. The emission spectra show that the tuning range of the color emission of the phosphors is between 498 and 440 nm, which is determined by x, under the excitation of UV. The wavelength of afterglow increases with increasing x until x equals 0.6, and when x equals 0.6, the luminescence property of Ba(1-x) Ca(x)Al2O4: Eu2+, RE3+ (RE3+ = Dy3+, Nd3+) is similar to that of CaAl2O4 : Eu2+, RE3+. The XRD measurements were performed to investigate the single phase states of the samples, and it was found that the single phase limit in the phosphors is below an x value of 0.4. The thermoluminescence curves imply that the traps in the hosts are different with different x value, which well explains the varying delay time of the samples.