[The Effect of CYP4 F2 Polymorphism on Initial Warfarin Dose in Patients with Heart Valve Replacement].

OBJECTIVE: To study the effect of cytochrome P-4504F2 ( CYP4 F2) gene polymorphism on the initial dose of warfarin in patients after mechanical heart valve replacement. METHODS: We collected 350 patients receiving warfarin after mechanical heart valve replacement from January 2013 to December 2015 in our hospital. According to the international standardized ratio (INR) ≥2 at the initial stage after surgery, the patients were divided into two groups: INR≥2 group and INR<2 group. We selected the blood samples of all the 350 patients with testing the CYP4 F2 gene type of each patient, and analyzed the effect of CYP4 F2 gene polymorphism on the initial dose of warfarin after mechanical heart valve replacement (the average daily dose during hospitalization of patients 5-10 days after mechanical heart valve replacement). RESULTS: There was no statistical significance in the initial dose of warfarin among patients with different CYP4 F2 genotypes. However, warfarin dose was higher in CYP4 F2 TT genotype than in CYP4 F2 CC carriers ((3.37±0.68) mg vs. (2.94±0.74) mg, P<0.05) in INR≥2 group; In patients with the same genotype, the initial dose of warfarin in the CYP4 F2 CC ((4.02±0.58) mg vs. (2.94±0.74) mg) and CYP4 F2 CT genotypes ((4.15±0.88) mg vs. (3.18±0.82) mg) of INR<2 group was higher than that in INR≥2 group ( P<0.05). Gender, age, body mass index (BMI), comorbidities (hypertension, diabetes mellitus, coronary heart disease, atrial fibrillation), cytopigment P-450 2C9 ( CYP2 C9), CYP4 F2 and vitamin K peroxide-reductase complex 1 ( VKORC1) gene polymorphism and INR compliance were included in multiple linear regression analysis. The regression equation was as follows: warfarin initial dose (mg) =-8.634+0.352×BMI (kg/m 2) +1.102× CYP4 F2 genotype (CC or CT values 1, TT values 2) +2.147× VKORC1 (AA or AG values 1, GG values 2) +1.325×INR ( INR≥2 values 0, INR<2 values 1). The coefficient of determination ( R 2) of regression equation was 0.431 ( P<0.05). CONCLUSION: CYP4 F2 gene polymorphism may affect the initial dose of warfarin in patients after heart valve replacement, and this effect is also affected by body characteristics and other factors.

Long non-coding RNA HOTAIR functions as a competitive endogenous RNA to regulate PRAF2 expression by sponging miR-326 in cutaneous squamous cell carcinoma.

BACKGROUND: LncRNAs may exert a regulatory effect in tumorigenesis. Although the expression of lncRNA HOTAIR has been confirmed to be notably elevated in the tissues of CSCC, its biological mechanism in CSCC is still unknown. METHODS: HOTAIR expression level in CSCC cell lines was monitored via qRT-PCR. Then CCK-8 assay, Transwell assay and EdU assay were adopted to detect cell migration and proliferation. Meanwhile, through bioinformatics analysis and luciferase reporter gene detection, a new target of HOTAIR was identified. Additionally, Western blotting and RIP analysis were adopted to discuss the possible mechanism. RESULTS: HOTAIR expression in CSCC cell lines exhibited an obvious elevation. Cell function analysis revealed that HOTAIR overexpression remarkably facilitated CSCC cell migration, proliferation and EMT process, which were impeded by down-regulation of HOTAIR. Furthermore, HOTAIR competitively bound to miR-326, so as to positively modulate miR-326 expression. CONCLUSIONS: These results present that HOTAIR, as a ceRNA, regulates PRAF2 expression by competitive binding to miR-326 during CSCC.

Tumor stroma-targeted antibody-drug conjugate triggers localized anticancer drug release.

Although nonmalignant stromal cells facilitate tumor growth and can occupy up to 90% of a solid tumor mass, better strategies to exploit these cells for improved cancer therapy are needed. Here, we describe a potent MMAE-linked antibody-drug conjugate (ADC) targeting tumor endothelial marker 8 (TEM8, also known as ANTXR1), a highly conserved transmembrane receptor broadly overexpressed on cancer-associated fibroblasts, endothelium, and pericytes. Anti-TEM8 ADC elicited potent anticancer activity through an unexpected killing mechanism we term DAaRTS (drug activation and release through stroma), whereby the tumor microenvironment localizes active drug at the tumor site. Following capture of ADC prodrug from the circulation, tumor-associated stromal cells release active MMAE free drug, killing nearby proliferating tumor cells in a target-independent manner. In preclinical studies, ADC treatment was well tolerated and induced regression and often eradication of multiple solid tumor types, blocked metastatic growth, and prolonged overall survival. By exploiting TEM8+ tumor stroma for targeted drug activation, these studies reveal a drug delivery strategy with potential to augment therapies against multiple cancer types.

Proteome exploration to provide a resource for the investigation of Ganoderma lucidum.

Ganoderma lucidum is a basidiomycete white rot fungus that has been used for medicinal purposes worldwide. Although information concerning its genome and transcriptome has recently been reported, relatively little information is available for G. lucidum at the proteomic level. In this study, protein fractions from G. lucidum at three developmental stages (16-day mycelia, and fruiting bodies at 60 and 90 days) were prepared and subjected to LC-MS/MS analysis. A search against the G. lucidum genome database identified 803 proteins. Among these proteins, 61 lignocellulose degrading proteins were detected, most of which (49 proteins) were found in the 90-day fruiting bodies. Fourteen TCA-cycle related proteins, 17 peptidases, two argonaute-like proteins, and two immunomodulatory proteins were also detected. A majority (470) of the 803 proteins had GO annotations and were classified into 36 GO terms, with "binding", "catalytic activity", and "hydrolase activity" having high percentages. Additionally, 357 out of the 803 proteins were assigned to at least one COG functional category and grouped into 22 COG classifications. Based on the results from the proteomic and sequence alignment analyses, a potentially new immunomodulatory protein (GL18769) was expressed and shown to have high immunomodulatory activity. In this study, proteomic and biochemical analyses of G. lucidum were performed for the first time, revealing that proteins from this fungus can play significant bioactive roles and providing a new foundation for the further functional investigations that this fungus merits.

Genome analysis of medicinal Ganoderma spp. with plant-pathogenic and saprotrophic life-styles.

Ganoderma is a fungal genus belonging to the Ganodermataceae family and Polyporales order. Plant-pathogenic species in this genus can cause severe diseases (stem, butt, and root rot) in economically important trees and perennial crops, especially in tropical countries. Ganoderma species are white rot fungi and have ecological importance in the breakdown of woody plants for nutrient mobilization. They possess effective machineries of lignocellulose-decomposing enzymes useful for bioenergy production and bioremediation. In addition, the genus contains many important species that produce pharmacologically active compounds used in health food and medicine. With the rapid adoption of next-generation DNA sequencing technologies, whole genome sequencing and systematic transcriptome analyses become affordable approaches to identify an organism's genes. In the last few years, numerous projects have been initiated to identify the genetic contents of several Ganoderma species, particularly in different strains of Ganoderma lucidum. In November 2013, eleven whole genome sequencing projects for Ganoderma species were registered in international databases, three of which were already completed with genomes being assembled to high quality. In addition to the nuclear genome, two mitochondrial genomes for Ganoderma species have also been reported. Complementing genome analysis, four transcriptome studies on various developmental stages of Ganoderma species have been performed. Information obtained from these studies has laid the foundation for the identification of genes involved in biological pathways that are critical for understanding the biology of Ganoderma, such as the mechanism of pathogenesis, the biosynthesis of active components, life cycle and cellular development, etc. With abundant genetic information becoming available, a few centralized resources have been established to disseminate the knowledge and integrate relevant data to support comparative genomic analyses of Ganoderma species. The current review carries out a detailed comparison of the nuclear genomes, mitochondrial genomes and transcriptomes from several Ganoderma species. Genes involved in biosynthetic pathways such as CYP450 genes and in cellular development such as matA and matB genes are characterized and compared in detail, as examples to demonstrate the usefulness of comparative genomic analyses for the identification of critical genes. Resources needed for future data integration and exploitation are also discussed.

Deep insight into the Ganoderma lucidum by comprehensive analysis of its transcriptome.

BACKGROUND: Ganoderma lucidum is a basidiomycete white rot fungus and is of medicinal importance in China, Japan and other countries in the Asiatic region. To date, much research has been performed in identifying the medicinal ingredients in Ganoderma lucidum. Despite its important therapeutic effects in disease, little is known about Ganoderma lucidum at the genomic level. In order to gain a molecular understanding of this fungus, we utilized Illumina high-throughput technology to sequence and analyze the transcriptome of Ganoderma lucidum. METHODOLOGY/PRINCIPAL FINDINGS: We obtained 6,439,690 and 6,416,670 high-quality reads from the mycelium and fruiting body of Ganoderma lucidum, and these were assembled to form 18,892 and 27,408 unigenes, respectively. A similarity search was performed against the NCBI non-redundant nucleotide database and a customized database composed of five fungal genomes. 11,098 and 8, 775 unigenes were matched to the NCBI non-redundant nucleotide database and our customized database, respectively. All unigenes were subjected to annotation by Gene Ontology, Eukaryotic Orthologous Group terms and Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes from the Ganoderma lucidum mycelium and fruiting body stage were analyzed, resulting in the identification of 13 unigenes which are involved in the terpenoid backbone biosynthesis pathway. Quantitative real-time PCR was used to confirm the expression levels of these unigenes. Ganoderma lucidum was also studied for wood degrading activity and a total of 22 putative FOLymes (fungal oxidative lignin enzymes) and 120 CAZymes (carbohydrate-active enzymes) were predicted from our Ganoderma lucidum transcriptome. CONCLUSIONS: Our study provides comprehensive gene expression information on Ganoderma lucidum at the transcriptional level, which will form the foundation for functional genomics studies in this fungus. The use of Illumina sequencing technology has made de novo transcriptome assembly and gene expression analysis possible in species that lack full genome information.

catena-Poly[[[tetra-aqua-copper(II)]-µ-4,4'-bipyridyl-κ(2)N:N'] tetra-fluorido-succinate tetra-hydrate].

In the title compound, {[Cu(C(10)H(8)N(2))(H(2)O)(4)](C(4)F(4)O(4))·4H(2)O}(n), the Cu(II) atom adopts an elongated octa-hedral geometry because of the Jahn-Teller effect. Both cation and anion have crystallographic twofold rotation symmetry with the twofold axes passing through the Cu and N atoms and through the midpoint of the central C-C bond. The 4,4'-bipyridyl ligand links the Cu(II) atoms into a linear chain along the b axis. O-H⋯O hydrogen-bonding inter-actions between the cationic chains and the tetra-fluorido-succinate anions and the free water mol-ecules generate a three-dimensional supra-molecular network.

[Clinical observation on analgesic effect of electroacupuncture at Neimadian after operation of extremities].

OBJECTIVE: To observe effectiveness and safety of electroacupuncture at Neimadian for analgesia in the extremities after orthopedic operation. METHODS: Two hundred cases enrolled were divided into two groups. The test group of 100 cases were treated with electroacupuncture at Neimadian and oral administration of placebo, and the control group of 100 cases with oral administration of tramadoli hydrochloride. RESULTS: The mean score for pain signs at all the time points before and after analgesic treatment in the test group had more decreases as compared with the control group (P < 0.001); and in the good rate after treatment, the test group was higher than the control group (P < 0.001, P < 0.05), and for safety, the test group was higher than the control group (P < 0.001). CONCLUSION: The analgesic effect and safety of electroacupuncture at Neimadian are superior to the routine analgesic after operation of the extremities.

[Clinical observation on acupuncture at Neimadian for analgesia postoperation of extremities].

OBJECTIVE: To observe therapeutic effect of acupuncture at Neimadian on pain after operation of four limbs. METHODS: Sixty-two patients were randomly divided into an observation group and a control group, 31 cases in each group. The observation group were treated with electroacupuncture at Neimadian for 30 min, and the control group with oral administration of tramadoli hydrochloridum. Changes of pain within 24 hours were observed. RESULTS: The analgesic effect in the observation group was better than that in the control group (P < 0.05). CONCLUSION: Analgesic effect of acupuncture at Neimadian on pain after operation of four limbs is superior to that of oral administration of tramadoli.