LncRNA ANRIL Promotes Autophagy Activation Through miR-16-5p/TLR4 Axis in Allergic Rhinitis.

BACKGROUND: Allergic rhinitis (AR) is an allergic disease of nasal mucosa. LncRNAs are key modulators affecting AR development. Neverthelss, the impact of lncRNA ANRIL in AR is not clear. OBJECTIVE: This work decided to study the mechanism underlying the impact of ANRIL on TLR4 expression through targeting miR-16-5p during autophagy and epithelial barrier dysfunction in the progression of AR. METHODS: Human nasal epithelial cells were exposed to TNF-α to establish AR cell model, AR mice model was constructed by ovalbumin (OVA) treatment. QRT-PCR or western blot assays were applied to measure the levels of mRNA and proteins. Dual-luciferase reporter gene detection and RIP assay were conducted to verify the association between ANRIL and miR-16-5p. Autophagy flux assessment by mRFP-GFP-LC3 method was performed to detect autophagy level. RESULTS: AR progression could induce the autophagy, and the expressions of tight junction proteins were downregulated in AR cell model. Moreover, knockdown of ANRIL reversed the effect of AR on autophagy-related protein and tight junction proteins MiR-16-5p was found to be bound with ANRIL and miR-16-5p inhibitor could reverse ANRIL knockdown-induced downregulation of autophagy-related proteins and epithelial barrier dysfunction. In addition, miR-16-5p directly targeted TLR4. Furthermore, knockdown of ANRIL reversed miR-16-5p and TLR4 expression, autophagy level, and tight junction protein levels in nasal mucosa of AR mice. CONCLUSION: This study illustrated that ANRIL acted as a promotion factor in AR induced autophagy and epithelial barrier dysfunction by enhancing the expression of TLR4 via interacting with miR-16-5p.

[Congenital ectrodactyly caused by chromosome 10q24.31 duplication and its pathogenetic analysis].

In order to investigate the genetic variations and the clinical manifestations of a range of congenital ectrodactyly family and to summarize the split hand/foot malformation (SHFM) types and their related pathogenic genes, we conducted phenotypic analyses of patient's limbs by physical and X-ray examination. The haplotypes were analyzed by using the extracted genes from peripheral blood on D10S1709, D10S192, D10S597, D10S1693 and D10S587 loci, and the mutation duplication loci were confirmed by Array-CGH detection. The pathogenic factors and inheritance pattern of SHFM were analyzed based on family investigation and gene analysis. Results demonstrate the proband's phenotype is typically of a congenital SHFM which is manifested by missing bilateral index and middle fingers, short bilateral thumbs, deformed left ring finger with webbing of the skin missing at the middle finger; bilateral big toe with the second and the third toe missing, fourth and fifth toe fusion leading to a deformed toe separated from the first toe by the middle of the foot. The haplotype analyses show that there is a repeat of at least 610 kb in chromosome 10q24.31-10q24.32 region. Array-CGH analysis shows 10q24.31 (102 832 650-103 511 083) ×3. Our results demonstrate that the pathogenic gene variation of ectrodactyly in this family is due to duplication of 10q24.31 (102 832 650~103 511 083). The haplotype 165-251-289-219-102 can be used as a disease marker for detecting 10q24.31~10q24.32 allele for SHFM.

Short- and long-term efficacy and safety of triple vs. dual antithrombotic therapy in patients with drug-eluting stent implantation and an indication for oral anticoagulation: a meta-analysis.

BACKGROUND: The optimal antithrombotic regimen after coronary stenting in patients taking oral anticoagulants (OACs) is still unclear. Therefore, this meta-analysis focused on the short- and long-term efficacy and safety of triple therapy (TT: OAC, aspirin, and thienopyridine) and dual therapy (DT: OAC plus single antiplatelet drug or aspirin plus thienopyridine). METHODS: We searched PubMed, Embase, the Cochrane Library, Wangfang database, and Google Scholar up to December 1, 2015 (January 1, 2000 - December 2015), from randomized and nonrandomized studies comparing TT and DT in patients with OACs undergoing drug-eluting stent (DES) implantation. Major adverse cardiac and cerebrovascular events (MACCE) were the main outcome. Safety outcome was major bleeding (MB). RESULTS: Of 964 publications identified, 1 randomized study and 27 nonrandomized studies of 31,346 patients were included. Overall, TT and OAC plus clopidogrel were associated with a lower risk of MACCE, stroke, MI, and allcause mortality compared with dual antiplatelet therapy or OAC plus aspirin. Additionally, short-term use of triple antithrombotic regimen with OAC, aspirin, and clopidogrel is associated with equivalent risk of major bleeding and decreased rate of MACCE. Long-term use of OAC plus clopidogrel after TT was associated with equal or better benefit and safety outcomes. CONCLUSION: For patients on OAC after coronary stenting, triple therapy (OAC, aspirin, clopidogrel) should be considered in the short term, followed by more long-term therapy with OAC plus clopidogrel. More randomized studies are needed to confirm these findings.

Transcriptome sequencing and analysis of rubber tree (Hevea brasiliensis Muell.) to discover putative genes associated with tapping panel dryness (TPD).

BACKGROUND: Tapping panel dryness (TPD) involves in the partial or complete cessation of latex flow thus seriously affect latex production in rubber tree (Hevea brasiliensis). Numerous studies have been conducted to define its origin and nature, but the molecular nature and mechanism of TPD occurrence remains unknown. This study is committed to de novo sequencing and comparative analysis of the transcriptomes of healthy (H) and TPD-affected (T) rubber trees to identify the genes and pathways related to the TPD. RESULTS: Total raw reads of 34,632,012 and 35,913,020 bp were obtained from H and T library, respectively using Illumina Hiseq 2000 sequencing technology. De novo assemblies yielded 141,456 and 169,285 contigs, and 96,070 and 112,243 unigenes from H and T library, respectively. Among 73597 genes, 22577 genes were identified as differential expressed genes between H and T library via comparative transcript profiling. A majority of genes involved in natural rubber biosynthesis and jasmonate synthesis with most potential relevance in TPD occurrence were found to be differentially expressed. CONCLUSIONS: In TPD-affected trees, the expression of most genes related to the latex biosynthesis and jasmonate synthesis was severely inhibited and is probably the direct cause of the TPD. These new de novo transcriptome data sets provide a significant resource for the discovery of genes related to TPD and improve our understanding of the occurrence and maintainace of TPD.

Synthesis and antitumor activities of novel thiourea α-aminophosphonates from dehydroabietic acid.

A series of novel thiourea α-aminophosphonate derivatives containing DHA structure was designed and synthesized as antitumor agents. Their inhibitory activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver) and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in vitro. The screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which indicated that the compound can induce cell apoptosis in A549 cells.

Synthesis and antitumor activities of novel α-aminophosphonates dehydroabietic acid derivatives.

A series of novel α-aminophosphonate derivatives containing DHA structure were designed and synthesized as antitumor agents. In vitro antitumor activities of these compounds against the NCI-H460 (human lung cancer cell), A549 (human lung adenocarcinoma cell), HepG2 (human liver cancer cell) and SKOV3 (human ovarian cancer cell) human cancer cell lines were evaluated and compared with commercial anticancer drug 5-fluorouracil (5-FU), employing standard MTT assay. The pharmacological screening results revealed that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most demonstrated more potent inhibitory activities compared with the commercial anticancer drug 5-FU. The action mechanism of representative compound 7c was preliminarily investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound can induce cell apoptosis in NCI-H460 cells. Cell cycle analysis showed that compound 7c mainly arrested NCI-H460 cells in G1 stage.

Indium(III) chloride catalyzed conjugate addition reaction of alkynylsilanes to acrylate esters.

A novel and efficient procedure for the synthesis of δ,γ-alkynyl esters by the conjugate addition of alkynylsilanes to acrylate esters in the presence of a catalytic amount of indium(III) chloride has been developed. This method provides a rapid and efficient access to substituted δ,γ-alkynyl esters.

Three new antioxidant C-glucosylanthrones from Aloe nobilis.

Three new C-glucosylanthrones, 3'-O-acetyl-5-hydroxylaloin A (2), 2',6'-O-diacetyl-5-hydroxylaloin A (4), and 4',6'-O-diacetyl-5-hydroxylaloin A (5), along with three known compounds, 5-hydroxyaloin A (1), 6'-acetyl-5-hydroxylaloin A (3), and 4-methoxy-6-(2',4'-dihydroxy-6'-methylphenyl)-pyran-2-one (6), were isolated from the leaves of Aloe nobilis, and their structures were elucidated on the basis of spectroscopic evidences. Compounds 1, 2, 4 and 5 showed antioxidant activity with inhibitory rates of 31.0, 34.0, 34.0, and 42.0%, respectively, at 10(-5) M.

BACE1 (beta-secretase) inhibitory phenolic acids and a novel sesquiterpenoid from Homalomena occulta.

Four phenolic acids, namely 2-[(Z)-heptadec-11-enyl]-6-hydroxybenzoic acid (1), 2-[(6Z,9Z,12Z)-heptadeca-6,9,12-trienyl]-6-hydroxybenzoic acid (2), 2-[(9Z,12Z)-heptadeca-9,12-dienyl]-6-hydroxybenzoic acid (3), and 2-hydroxy-6-(12-phenyldodecyl)benzoic acid (4), and one sesquiterpene, asperpenoid (5), were isolated from the 95% EtOH extract of the roots of Homalomena occulta, among which 1, 2, and 5 represent new compounds. Further, the phenolic acids 1-4 exhibited BACE1 (beta-secretase) inhibitory activity with IC(50) values of 6.23+/-0.94, 6.28+/-0.63, 7.93+/-0.38, and 7.65+/-0.62 microM, respectively.

Jacaranone analogs from Senecio scandens.

Bioassay-guided fractionation of the ethanolic extract of Senecio scandens led to the isolation of four new compounds 4, 5, 7, and 8, along with four known jacaranone analogs (1, 2, 3, 6). Their structures were elucidated on the basis of spectral and chemical evidence. Compound 7 was obtained as a tautomeric mixture of alpha/beta-epimer. The cytotoxic activities of these compounds were evaluated. Among these, compounds 5 and 8 showed potent cytotoxicities. The benzoquinone derivative, jacaranone ethyl ester (1), was the major cytotoxic constituent in this plant with IC(50)s at a range of 0.5-1.0 microg/ml against various tumor cell lines. The SAR of these jacaranone analogs (1-8), isolated from S. scandens, was also discussed.

[Clinical value of noninvasive positive-pressure ventilation in chronic obstruction pulmonary disease combined with type II respiratory failure: a 4-year retrospective study].

OBJECTIVE: To evaluate the value of noninvasive positive-pressure ventilation (NIPPV) in treatment of patients with chronic obstruction pulmonary disease (COPD) combined with type II respiratory failure (RF). METHODS: From June 15th, 2002 to June 15th, 2006, there were 351 inpatients with COPD combined with type II RF. Those treated with NIPPV were categorized as treatment group; those who were not treated by NIPPV served as control group. All patients were divided into four subgroups according to results of blood gas analysis as follows. Mild RF group: 50 mm Hg < or = arterial partial pressure of carbon dioxide (PaCO2) < or = 65 mm Hg, 1 mm Hg=0.133 kPa; medium RF group: 66 mm Hg < or = PaCO2 < or = 80 mmHg; severe RF group: 81 mm Hg < or = PaCO2 < or = 95 mm Hg; extremely severe RF group: > or = 96 mm Hg. NIPPV was used in treatment group on top of conventional treatment. Values of blood gas analysis, length of stay, cost of hospitalization, rate of cannulation and fatality rate were observed in all groups before treatment and after treatment. RESULTS: After being treated with NIPPV, all patients with COPD combined with type II RF in different degrees, arterial partial pressure of oxygen (PaO2) were raised in different degrees, and PaCO2 were all lowered in different degrees. Blood pH, PaO2 and PaCO2 showed statistically significant difference between treatment group and control group in severe and extremely severe RF patients (all P < 0.05). The length of stay of patients with RF in different degrees, was shortened obviously, also the cost of hospitalization, rate of cannulation and fatality rate were all significantly reduced in treatment group. In contrast to mild, medium RF patients, rate of cannulation and fatality rate were increased in extremely severe RF group (all P < 0.05). CONCLUSION: NIPPV is beneficial to COPD combined with type II RF in different degrees.

Alfacalcidol treatment increases bone mass from anticatabolic and anabolic effects on cancellous and cortical bone in intact female rats.

It has been reported that alfacalcidol had an anticatabolic and anabolic effect on bone in ovariectomized and aged male rat models, but this has not been tested on intact female rats. The current study was to determine the effects of alfacalcidol on cancellous and cortical bone in intact female rats with or without exercise. Seventy-four, 8.5-month-old, intact female rats were orally treated with 0, 0.005, 0.025, 0.05, or 0.1 microg/kg alfacalcidol alone or in combination with raised cage (RC) exercise for 3 months. In vivo peripheral quantitative computerized tomography (pQCT) of the proximal tibial metaphyses (PTM) and ex vivo histomorphometric analyses of the PTM and tibial shaft (TX) were performed. Only the 0.1 microg alfacalcidol/kg dose proved to be anabolic. pQCT analysis showed that this dose increased total and cortical bone mineral content and density and trabecular bone mineral density. Histomorphometrically, it induced an anabolic response by increased trabecular mass and microarchitecture from stimulated cancellous bone and bone bouton formations, and suppressed bone resorption more than bone formation on the trabecular and endocortical surfaces, to produce a positive bone balance. A positive correlation between trabecular connectivity and bone bouton numbers occurred. These findings suggest alfacalcidol treatment augments bone mass by increased cancellous bone mass and improved trabecular architecture through its anticatabolic and anabolic properties in the intact adult female rat. Last, raised cage exercise alone or the combination of raised cage and alfacalcidol was no more effective than alfacalcidol alone.

On the chemical constituents of Dipsacus asper.

Bioassay-guided fractionation of 95% EtOH extract from the roots of Dipsacus asper lead to the isolation of some phenolic acids (caffeic acid, 2,6-dihydroxycinnamic acid, vanillic acid, 2'-O-caffeoyl-D-glucopyranoside ester, and caffeoylquinic acid) as the major active components, and five new iridoid glucoside dimers (1-5) and one new iridoid glucoside monomer (6), other known iridoid glycosides loganin, cantleyoside, triplostoside A, lisianthioside, 6'-O-beta-D-apiofuranosyl sweroside, as well as triterpenoids oleanic acid and akebiasaponin D. The structures of new compounds 1-6 were determined as dipsanosides C (1), D (2), E (3), F (4), G (5), and 3'-O-beta-D-glucopyranosyl sweroside (6) by spectroscopic, including 1D and 2D NMR techniques, and chemical methods.

Jacaranone glycosides from Senecio scandens.

Bioassay-guided fractionation of the ethanol extract of Senecio scandens led to the isolation of four new compounds 1-4. These compounds were obtained as tautomeric mixture of alpha/beta epimers, but their structures were confirmed unambiguously by 1D and 2D NMR spectra and LC NMR technology. 1H NMR spectra of pure 1alpha and 1beta were furnished by HPLC NMR technology. Compounds 1-4 exhibited moderate cytotoxicities against five tumor cell lines.

Two novel tetrairidoid glucosides from Dipsacus asper.

[reaction: see text] Two new iridoid glucoside tetramers, dipsanosides A (1) and B (2), the first-reported iridoid tetramers with four glucosides, were isolated from Dipsacus asper. Their structures were determined by analysis of 1D and 2D NMR data as well as by comparison with model compounds. Their cytotoxicities were tested, but neither of them showed obvious activity.

A nonprostanoid EP4 receptor selective prostaglandin E2 agonist restores bone mass and strength in aged, ovariectomized rats.

UNLABELLED: CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 agonist. CP432 stimulates trabecular and cortical bone formation and restores bone mass and bone strength in aged ovariectomized rats with established osteopenia. INTRODUCTION: The purpose of this study was to determine whether a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 (PGE2) agonist, CP432, could produce bone anabolic effects in aged, ovariectomized (OVX) rats with established osteopenia. MATERIALS AND METHODS: CP432 at 0.3, 1, or 3 mg/kg/day was given for 6 weeks by subcutaneous injection to 12-month-old rats that had been OVX for 8.5 months. The effects on bone mass, bone formation, bone resorption, and bone strength were determined. RESULTS: Total femoral BMD increased significantly in OVX rats treated with CP432 at all doses. CP432 completely restored trabecular bone volume of the third lumbar vertebral body accompanied with a dose-dependent decrease in osteoclast number and osteoclast surface and a dose-dependent increase in mineralizing surface, mineral apposition rate, and bone formation rate-tissue reference in OVX rats. CP432 at 1 and 3 mg/kg/day significantly increased total tissue area, cortical bone area, and periosteal and endocortical bone formation in the tibial shafts compared with both sham and OVX controls. CP432 at all doses significantly and dose-dependently increased ultimate strength in the fifth lumber vertebral body compared with both sham and OVX controls. At 1 and 3 mg/kg/day, CP432 significantly increased maximal load in a three-point bending test of femoral shaft compared with both sham and OVX controls. CONCLUSIONS: CP432 completely restored trabecular and cortical bone mass and strength in established osteopenic, aged OVX rats by stimulating bone formation and inhibiting bone resorption on trabecular and cortical surfaces.