Genome-wide study refines the quantitative trait locus for number of ribs in a Large White × Minzhu intercross pig population and reveals a new candidate gene.

In China, sparerib is one of the most valuable parts of the pork carcass. As a result, candidate gene mining for number of ribs has become an interesting study focus. To examine the genetic basis for this major trait, we genotyped 596 individuals from an F2 Large White × Minzhu intercross pig population using the PorcineSNP60 Genotyping BeadChip. The genome-wide association study identified a locus for number of ribs in a 2.38-Mb region on Sus scrofa chromosome 7 (SSC7 of Sus scrofa genome assembly, Sscrofa10.2). We identified the top significant SNP ASGA0035536, which explained 16.51 % of the phenotypic variance. A previously reported candidate causal mutation (g.19034 A>C) in vertebrae development-associated gene VRTN explained 8.79 % of the phenotypic variation on number of ribs and had a much lower effect than ASGA0035536. Haplotype sharing analysis in F1 boars localized the rib number QTL to a 951-kb interval on SSC7. This interval encompassed 17 annotated genes in Sscrofa10.2, including the previously reported VRTN candidate gene. Of the 17 candidate genes, LTBP2, which encodes a latent transforming growth factor beta binding protein, was previously reported to indirectly regulate the activity of growth differentiation factor Gdf11, which has been shown to increase the number of ribs in knock-out mice. Thus, we propose LTBP2 as a good new candidate gene for number of ribs in the pig population. This finding advances our understanding of the genetic architecture of rib number in pigs.

A Porous Tricyclooxacalixarene Cage Based on Tetraphenylethylene.

A quadrangular prismatic tricyclooxacalixarene cage 1 based on tetraphenylethylene (TPE) was efficiently synthesized by a one-pot S(N)Ar condensation reaction. As a result of the porous internal structure in the solid state, cage 1 exhibited a good CO2 uptake capacity of 12.5 wt% and a high selectivity for CO2 over N2 adsorption of 80 (273 K, 1 bar) with a BET surface area of 432 m(2) g(-1). Formation of cage 1 led to the fluorescence of TPE being switched on in solution. The system was employed as a single-molecule platform to study the mechanism of aggregation-induced emission (AIE) by examining the restriction of intramolecular rotation (RIR).

Tetraphenylethylene-based expanded oxacalixarene: synthesis, structure, and its supramolecular grid assemblies directed by guests in the solid state.

A novel TPE-based expanded oxacalixarene with typical aggregation-induced emission properties was synthesized by the SNAr reaction of dihydroxytetraphenylethylene with 2,6-dichloropyrazine. The conformation of the oxacalixarene is adjusted by the encapsulated guests (benzene or THF), which results in different supramolecular grid structures in the solid state.

A genome-wide association study of limb bone length using a Large White × Minzhu intercross population.

BACKGROUND: In pig, limb bone length influences ham yield and body height to a great extent and has important economic implications for pig industry. In this study, an intercross population was constructed between the indigenous Chinese Minzhu pig breed and the western commercial Large White pig breed to examine the genetic basis for variation in limb bone length. The aim of this study was to detect potential genetic variants associated with porcine limb bone length. METHODS: A total of 571 F2 individuals from a Large White and Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for femur length (FL), humerus length (HL), hipbone length (HIPL), scapula length (SL), tibia length (TL), and ulna length (UL). A genome-wide association study was performed by applying the previously reported approach of genome-wide rapid association using mixed model and regression. Statistical significance of the associations was based on Bonferroni-corrected P-values. RESULTS: A total of 39 significant SNPs were mapped to a 11.93 Mb long region on pig chromosome 7 (SSC7). Linkage analysis of these significant SNPs revealed three haplotype blocks of 495 kb, 376 kb and 492 kb, respectively, in the 11.93 Mb region. Annotation based on the pig reference genome identified 15 genes that were located near or contained the significant SNPs in these linkage disequilibrium intervals. Conditioned analysis revealed that four SNPs, one on SSC2 and three on SSC4, showed significant associations with SL and HL, respectively. CONCLUSIONS: Analysis of the 15 annotated genes that were identified in these three haplotype blocks indicated that HMGA1 and PPARD, which are expressed in limbs and influence chondrocyte cell growth and differentiation, could be considered as relevant biological candidates for limb bone length in pig, with potential applications in breeding programs. Our results may also be useful for the study of the mechanisms that underlie human limb length and body height.

Supramolecular gel-assisted formation of fullerene nanorods.

Gel it like it is: Fullerene nanorods (see figure) with a length of several micrometers, can be easily synthesized by a supramolecular gel-assisted self-assembly method (SGAS). The results presented here may be useful for the design and construction of new organic nanomaterials by SGAS.

Inactivation of GABA transaminase by 3-chloro-1-(4-hydroxyphenyl)propan-1-one.

Previously it was found that 4-hydroxybenzaldehyde is a competitive inhibitor of GABA transaminase. Here 3-chloro-1-(4-hydroxyphenyl)propan-1-one (9), a 4-hydroxybenzaldehyde analogue, was found to inactivate potently the enzyme in a time-dependent manner. alpha-Ketoglutarate prevented the enzyme from inactivation, suggesting that the inactivation occurs in its active site. Several experiments indicated that the inactivation is irreversible. This study provides a novel strategy for the design of more effective inhibitors.

Anti-arrhythmic effects of kappa-opioid receptor and its changes in ischemia and reperfusion.

BACKGROUND: It remains unclear whether the kappa-opioid receptor (kappa-OR) is altered during ischemia and reperfusion. Therefore, the present study was designed to investigate changes in the kappa-OR. Additionally, the anti-arrhythmic effect induced by kappa-OR stimulation was also determined during ischemia and reperfusion (I/R). METHODS: Rats were randomly divided into different groups according to two experimental protocols. The anti-arrhythmic effects of U50,488H, a selective kappa-OR agonist, in an I/R model of 15-min ischemia were studied followed by 15 min of reperfusion. The content of kappa-OR mRNA and protein were measured by RT-PCR and Western blotting techniques in an I/R model of 30-min ischemia followed by 360 min of reperfusion. RESULTS: Limited numbers of premature ventricular contractions (PVCs) were revealed in the control group. Administration of U50,488H in the control group had no effect on occurrence of PVCs. Incidence of arrhythmia in the I/R group was significantly increased. Treated with U50,488H in the I/R group, the incidence of arrhythmia was significantly reduced. With prior use of nor-BNI, a selective kappa-OR antagonist, the anti-arrhythmic effect of U50,488H was completely blocked. Compared with the control group, the content of kappa-OR mRNA and the density of kappa-OR protein increased significantly at 0 min, 60 min, and 180 min during reperfusion. CONCLUSIONS: The present study provides evidence for the first time that the expressions of kappa-OR mRNA and protein are upregulated in the heart of I/R rats. This alteration may produce a strengthened anti-arrhythmic effect upon kappa-OR stimulation during I/R.

[Microstructure of novel solid lipid nanoparticle loaded triptolide].

Novel solid lipid nanoparticle (SLN) system is prepared with Compritol ATO 888 and tricaprylic glyceride. DSC, XRD, SAXS and NMR are employed to study the novel carrier property and microstructure. When the peak melting point decreased from 70.8 degrees C to 61.4 degrees C, the enthalpy sharply decreased. It could be concluded that the regular crystal lattices in the novel carriers are broken out for the oil joined in them. Melting behavior is occurred at -17.7 degrees C while novel SLN is composed of oil and solid lipid mixture from the DSC measurement. Most alpha phase and least beta' phase are in the nano carrier system whether drug loading or not from the XRD investigation. There is only 0.1 nm change of long space among the novel SLN made of mixture and the lipid matrix and traditional SLN; therefore, it is impossible of the oil molecular insert into the solid glyceride structure. Since the different melting behavior (DSC measurements) and molecular move state (NMR investigations), two lipid matrix are still in two state of liquid and solid lipid in the novel SLN carrier. Presume the microstructure of the novel SLN prepared by our experiment would be that liquid oil has formed superfine nano accommodation encapsulated with solid lipid, but the whole particle is still in nano size range.

Puerarin protects rat pancreatic islets from damage by hydrogen peroxide.

The protective effect of puerarin, an isoflavone purified from Chinese herb radix of Pueraria lobata, on hydrogen peroxide (H(2)O(2))-induced rat pancreatic islets damage was investigated. Exposure of islets to 500 microM H(2)O(2) could cause a significant viability loss and an increase in apoptotic rate. Pretreatment of islets with puerarin for 48 h resulted in a reduction in viability loss and apoptotic rate. 100 microM puerarin significantly inhibited the apoptosis of islets induced by H(2)O(2). In addition, preincubation with puerarin could restore the H(2)O(2)-induced decrease in basal and glucose-stimulated insulin secretion in pancreatic islets. Puerarin was also found to inhibit the free radicals production induced by H(2)O(2) and to increase catalase and superoxide dismutase (SOD) activities in the isolated pancreatic islets. These results suggest that puerarin can protect islets against oxidative stress probably due to stimulating the activities of the antioxidant enzymes. Puerarin may be effective in preventing islet cells from the toxic action of reactive oxygen species in diabetes.

Membrane-associated cytotoxicity induced by realgar in promyelocytic leukemia HL-60 cells.

Realgar has been shown to have a therapeutic effect against acute promyelocytic leukemia (APL) by inducing apoptosis. However, there is little data about the effects of it on plasma membrane. In the present study, the cytotoxicity of realgar to HL-60 cells including its inhibiting cell growth, inducing apoptosis and bringing about membrane toxicity was investigated. It was suggested that realgar could significantly suppress the proliferation of HL-60 cells in a dose-dependent manner by 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium bromide (MTT) assay and the IC50 value was 5.67 microM. Flow cytometric analysis revealed that treatment with realgar resulted in increased percentages of apoptotic cells in a dose-dependent manner. On the other hand, membrane lipid peroxidation level, lactate dehydrogenase (LDH) leakage and membrane surface topography alterations were investigated to assess the membrane toxicity induced by realgar. Treatment with realgar at different concentrations accelerated membrane lipid peroxidation, potentiated LDH leakage, which was consistent with enhanced disorganization of membrane surface observed by atomic force microscopy (AFM). These results suggested that such membrane toxicity induced by realgar might play an important role in the process of apoptotic induction and could be considered as one of mechanisms underlying the cytotoxicity of realgar.

Microporous Polymers from a Carbazole-Based Triptycene Monomer: Synthesis and Their Applications for Gas Uptake.

Two kinds of novel organic microporous polymers TCPs (TCP-A and TCP-B) were prepared by two cost-effective synthetic strategies from the monomer of tricarbazolyltriptycene (TCT). Their structure and properties were characterized by FT-IR, solid (13) C NMR, powder XRD, SEM, TEM, and gas absorption measurements. TCP-B displayed a high surface area (1469 m(2) g(-1) ) and excellent H2 storage (1.70 wt % at 1 bar/77 K) and CO2 uptake abilities (16.1 wt % at 1 bar/273 K), which makes it a promising material for potential application in gas storage.

Down-regulation of IL-8 expression in human airway epithelial cells through helper-dependent adenoviral-mediated RNA interference.

Interleukin (IL)-8 is a potent neutrophil chemotactic factor and a crucial mediator in neutrophil-dependent inflammation. Various cell types produce IL-8, either in response to external stimuli such as cytokines or bacterial infection, or after malignant transformation. Anti-IL-8 strategies have been considered for anti-inflammatory therapy. In this paper we demonstrate that the RNA interference technique can be used to efficiently down-regulate IL-8 protein expression in airway epithelial cells. We used a helper-dependent adenoviral vector to express a small hairpin (sh)RNA targeting human IL-8 in cultured airway epithelial cells (IB3-1, Cftr-/-; C38, Cftr-corrected) stimulated with TNF-alpha, IL-1beta or heat-inactivated Burkholderia cenocepacia. Stimulated IL-8 expression in IB3-1 and C38 cells was significantly reduced by shRNA expression. The shRNA targeting IL-8 had no effect on the activation of NF-kappaB, or on the protein levels of IkappaB or IL-6, suggesting that this anti-IL-8 strategy was highly specific, and therefore may offer potential for the treatment of inflammatory diseases.

Synthesis, characterization of novel injectable drug carriers and the antitumor efficacy in mice bearing Sarcoma-180 tumor.

New unsaturated polyesters of poly(fumaric acid-glycol-dodecanedioic acid) P(FA-GLY-DDDA) copolymers, poly(fumaric acid-glycol-brassylic acid) P(FA-GLY-BA) copolymers, poly(fumaric acid-glycol-tetradecanedioic acid) P(FA-GLY-TA) copolymers and poly(fumaric acid-glycol-pentadecanedioic acid) P(FA-GLY-PA) copolymers were prepared by melt polycondensation of the corresponding mixed monomers: fumaric acid, glycol and one of C(12-15) dibasic acids. The copolymers were characterized by FT-IR, gel permeation chromatography (GPC), and the surface structure of unsaturated polyesters after solidify were studied by atomic force microscopy (AFM). The molecular structure and composition of the unsaturated polyesters were determined by 1H NMR spectroscopy. In vitro studies showed that some of the copolymers are degradable in phosphate buffer at 37 degrees C and have properly drug release rate as drug carriers. The biocompatibility of P(FA-GLY-DDDA) and P(FA-GLY-BA) copolymers under mice skin was also evaluated, macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(FA-GLY-DDDA) copolymers and P(FA-GLY-BA) copolymers containing 5% adriamycin hydrochloride (ADM) in mice bearing Sarcoma-180 tumor exhibited increased volume doubling time (VDT) (22+/-1.5 days and 24+/-2.5 days) compared to plain subcutaneous injection of ADM (7+/-0.9 days). The antitumor efficacy of injecting P(FA-GLY-DDDA)-ADM inside tumor twice intervened in 22 days exhibited an especially increased cytotoxic effect as revealed by increased VDT (33+/-2.5 days), and the antitumor efficacy of injecting P(FA-GLY-BA)-ADM inside tumor twice intervened in 24 days exhibited an especially increased cytotoxic effect as revealed by increased VDT (35+/-1.5 days). The studies suggested that P(FA-GLY-DDDA) copolymers and P(FA-GLY-BA) copolymers as effective and injectable carriers for antineoplastic drug like adriamycin hydrochloride have a very good foreground in the treatment of noumenon tumor.

Influence of alloxan-induced diabetes and selenite treatment on blood glucose and glutathione levels in mice.

Many clinical studies reported that diabetic patients had lower glutathione contents in erythrocytes or plasma. Recently, selenium, an essential trace element with well-known antioxidant characteristics, has been found to have insulin-mimetic properties. But seldom information is available about the influence of selenium on glutathione changes induced by diabetes mellitus in animals. Therefore, this study was designed to compare the impacts of selenite treatment on glutathione (GSH) levels of blood and tissues such as brain, kidney, liver, spleen and testis in mice. Four groups were used in this study: a control group, a diabetic group, a selenite-treated normal group and a selenite-treated diabetic group. Selenite was administered to the mice for 4 weeks with an oral dose of 2 mg kg(-1) day(-1) by gavage. The blood glucose level, and GSH level in blood and tissues were determined. The results show that the selenite-treated diabetic group had significantly lower blood glucose levels than the diabetic group. Moreover, alloxan-induced diabetes significantly decreased GSH levels in blood, kidney, liver and testis compared to the controls. Selenite treatment of the diabetic mice only improved the GSH levels in liver and brain. On the other hand, selenite administered to the normal mice reduced GSH levels in the liver compared to the controls. In conclusion, this study suggests that selenite treatment of diabetic mice with an effective dose would be beneficial for the antioxidant system of liver and brain although it exerts a toxic effect on the liver of normal mice.

Membrane toxicity accounts for apoptosis induced by realgar nanoparticles in promyelocytic leukemia HL-60 cells.

Previous studies have demonstrated that realgar nanoparticles might provide a less toxic agent for antineoplasia by suppressing angiogenesis. Here, we addressed the question of whether the size effects on apoptosis induction mainly contribute to the comparably higher concentration of easily soluble As2O3 present in realgar nanoparticles. Results revealed that treatment with realgar nanoparticles resulted in considerably low cell viability and produced characteristic apoptotic events in HL-60 cells, including morphological changes, DNA ladder formation, and increased number of cells with sub-G1-phase, whereas raw realgar particles with the same As2O3 concentration failed to induce apoptosis. On the other hand, the effects of realgar nanoparticles and raw realgar particles on cell membrane were examined. Realgar nanoparticles had acute toxicity to cell membrane, potentiating lipid peroxidation, increasing lactate dehydrogenase (LDH) release, and reducing membrane fluidity, whereas raw realgar particles had little effect on cell membrane besides a similar reduction of membrane fluidity. These results suggest that the promotion of lipid peroxidation and membrane permeability might play an important role in the process of apoptotic induction by realgar nanoparticles. However, raw realgar particles are not sufficient to elicit apoptosis, although they can reduce membrane fluidity in HL-60 cells.

[Isopropyl myristate molecular gels and drug-loaded transdermal capability].

AIM: To prepare of isopropyl myristate (IPM) molecular gels and investigate of its transdermal capability. METHODS: Microstructure of IPM gels was studied by scanning electron microscope (SEM) and optical microscope (OM). The rheology and thixotropy of IPM gels were investigated by viscosity. Triptolide was used as model drug to investigate its transdermal capability. RESULTS: The microstructure of IPM gels was a three-dimension network formed by the aggregation of Span 60 in IPM, which was rod-like tubular aggregate. It has good rheology and thixotropy. There was a good linear correlation between the accumulative permeated amount per unit area and the time for triptolide-loaded IPM gels. The permeation process agreed with zero order pharmacokinetics. The average permeability through rat skin for triptolide was 19.26 ng x cm(-2) x h(-1), which was 2.92 times of triptolide unguents obtained commercially available. CONCLUSION: Isopropyl myristate molercular gel can be formed by span 60 assemblies. Transdermal capability drug-loaded IPM gels was better than that of triptolide unguents.

[Progress in research on triptolide].

To further understand triptolide, this paper has introduced the pharmacology, pharmacokinetics, toxicity, the clinic application and semi-synthesis of triptolide on basis of importance and significant contents of reference which have been consulted in the past twenty years. Presently triptolide and Tripterygium wilfordii have been a hot spot of modernization of Chinese traditional medicine. It is very important to develop a new dosage form of high effect and low toxicity by making use of advanced technology according to its characteristics.

Temperature-sensitive fluorescent organic nanoparticles with aggregation-induced emission for long-term cellular tracing.

Temperature-sensitive organic nanoparticles with AIE effect were assembled in water from tetraphenylethene-based poly(N-isopropylacrylamide) (TPE-PNIPAM), which was synthesized by ATRP using TPE derivative as initiator. The size and fluorescence of TPE-PNIPAM nanoparticles can be tuned by varying the temperature. These nanoparticles can be internalized readily by HeLa cells and can be used as long-term tracer in live cells to be retained for as long as seven passages.

A polysaccharide-protein complex from Lycium barbarum upregulates cytokine expression in human peripheral blood mononuclear cells.

The production of cytokine is a key event in the initiation and regulation of an immune response. Many compounds are now used routinely to modulate cytokine production, and therefore the immune response, in a wide range of diseases, such as cancer. Interleukin-2 and tumor necrosis factor-alpha are two important cytokines in antitumor immunity. In this study, the effects of Lycium barbarum polysaccharide-protein complex (LBP(3p)) on the expression of interleukin-2 and tumor necrosis factor-alpha in human peripheral blood mononuclear cells were investigated by reverse transcription polymerase chain reaction (RT-PCR) and bioassay. Administration of LBP(3p) increased the expression of interleukin-2 and tumor necrosis factor-alpha at both mRNA and protein levels in a dose-dependent manner. The results suggest that LBP(3p) may induce immune responses and possess potential therapeutic efficacy in cancer.