SUMOylation of SIRT1 activating PGC-1α/PPARα pathway mediates the protective effect of LncRNA-MHRT in cardiac hypertrophy.

Long noncoding RNA-Myosin heavy chain associated RNA transcript (LncRNA-MHRT) has been reported to prevent pathological cardiac hypertrophy. However, the underlying inhibition mechanism has not been fully elucidated. Further, whether MHRT inhibits hypertrophy by regulating post-translational modification of certain proteins remains unclear. Therefore, this study aims to find potential role of MHRT in inhibiting cardiac hypertrophy via regulating modification of certain proteins. Here, Angiotensin II (Ang II) -treated neonatal rat cardiomyocytes and transverse aortic constriction (TAC) mice were used to investigate the effect and mechanism of MHRT in cardiac hypertrophy in vitro and in vivo. Moreover, the regulatory effects of MHRT on SUMOylation of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α)/peroxisome proliferator-activated receptor-α (PPARα), specificity protein 1 (SP1)/histone deacetylase 4 (HDAC4) pathway were investigated. Here, we found that MHRT improved heart function by attenuating pathological cardiac hypertrophy in vivo and in vitro. MHRT also promoted the SUMOylation of SIRT1 protein that activated PGC1-α/PPAR-α pathway. Furthermore, MHRT enhanced SUMOylation of SIRT1 by upregulating SP1/HDAC4. Our findings suggested that SUMOylation of SIRT1 could mediate the protective effect of MHRT in cardiac hypertrophy. The new regulatory pathway provides a potential new therapeutic target for pathological cardiac hypertrophy.

Cordyceps Improves Obesity and its Related Inflammation via Modulation of Enterococcus cecorum Abundance and Bile Acid Metabolism.

Dysbiotic gut microbiota has been identified as a primary mediator of inherent inflammation that underlies the pathogenesis of obesity. Cordyceps comprises the larval body and the stroma of Cordyceps sinensis (BerK.) Sacc. parasiting on Hepialidae larvae of moths (H. pialusoberthur) with potent metabolic regulation functions. The underlying anti-obesity mechanisms, however, remain largely unknown. Here, we demonstrate that the water extract of Cordyceps attenuates glucose and lipid metabolism disorders and its associated inflammation in high-fat diet (HFD)-fed mice. 16S rRNA gene sequencing and microbiomic analysis showed that Cordyceps reduced the amounts of Enterococcus cecorum, a bile-salt hydrolase-producing microbe to regulate the metabolism of bile acids in the gut. Importantly, E. cecorum transplantation or liver-specific knockdown of farnesoid X receptor (FXR), a bile acid receptor, diminished the protective effect of Cordyceps against HFD-induced obesity. Together, our results shed light on the mechanisms that underlie the glucose- and lipid-lowering effects of Cordyceps and suggest that targeting intestinalE. cecorum or hepatic FXR are potential anti-obesity and anti-inflammation therapeutic avenues.

Graphene Oxide and Reduced Graphene Oxide Exhibit Cardiotoxicity Through the Regulation of Lipid Peroxidation, Oxidative Stress, and Mitochondrial Dysfunction.

OBJECTIVE: Graphene has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to evaluate the cardiotoxicity of graphene oxide (GO) and reduced GO (rGO) in vitro and in vivo, as well as to investigate the underlying toxicity mechanisms. METHODS: GO was reduced by gamma irradiation to prepare rGO and then characterized by UV/visible light absorption spectroscopy. Rat myocardial cells (H9C2) were exposed to GO or rGO with different absorbed radiation doses. The in vitro cytotoxicity was evaluated by MTT assay, cell apoptosis assay, and lactate dehydrogenase (LDH) activity assay. The effects of GO and rGO on oxidative damage and mitochondrial membrane potential were also explored in H9C2 cells. For in vivo experiments, mice were injected with GO or rGO. The histopathological changes of heart tissues, as well as myocardial enzyme activity and lipid peroxidation indicators in heart tissues were further investigated. RESULTS: rGO was developed from GO following different doses of gamma irradiation. In vitro experiments in H9C2 cells showed that compared with control cells, both GO and rGO treatment inhibited cell viability, promoted cell apoptosis, and elevated the LDH release. With the increasing radiation absorbed dose, the cytotoxicity of rGO gradually increased. Notably, GO or rGO treatment increased the content of ROS and reduced the mitochondrial membrane potential in H9C2 cells. In vivo experiments also revealed that GO or rGO treatment damaged the myocardial tissues and changed the activities of several myocardial enzymes and the lipid peroxidation indicators in the myocardial tissues. CONCLUSION: GO exhibited a lower cardiotoxicity than rGO due to the structure difference, and the cardiotoxicity of GO and rGO might be mediated by lipid peroxidation, oxidative stress, and mitochondrial dysfunction.

MOF Nanosheet Reconstructed Two-Dimensional Bionic Nanochannel for Protonic Field-Effect Transistors.

The construction of hydrophobic nanochannel with hydrophilic sites for bionic devices to proximally mimick real bio-system is still challenging. Taking the advantages of MOF chemistry, a highly oriented CuTCPP thin film has been successfully reconstructed with ultra-thin nanosheets to produce abundant two-dimensional interstitial hydrophobic nanochannels with hydrophilic sites. Different from the classical active-layer material with proton transport in bulk, CuTCPP thin film represents a new type of active-layer with proton transport in nanochannel for bionic proton field-effect transistor (H+ -FETs). The resultant device can reversibly modulate the proton transport by varying the voltage on its gate electrode. Meanwhile, it shows the highest proton mobility of ≈9.5×10-3  cm2 V-1 s-1 and highest on-off ratio of 4.1 among all of the reported H+ -FETs. Our result demonstrates a powerful material design strategy for proximally mimicking the structure and properties of bio-systems and constructing bionic electrical devices.

Natural deep eutectic solvents as tailored and sustainable media for the extraction of five compounds from compound liquorice tablets and their comparison with conventional organic solvents.

An efficient and environmentally friendly ultrasound-assisted (UAE) natural deep eutectic solvent (NADES) extraction method was applied for the extraction of five bioactive compounds (liquiritin, isoliquiritin, liquiritigenin, glycyrrhizic acid and isoliquiritigenin) from compound liquorice tablets (CPLTs), and the antioxidant activities of these compounds were evaluated. In this study, eighteen different NADES systems based on either two or three components were tested and a 1,4-butanediol-levulinic acid system (1 : 3 molar ratio) was selected as a topgallant solvent for maximizing analyte extraction yields. Various extraction parameters, such as water content, liquid/solid ratio, extraction time and temperature, were systematically optimized by single-factor and response surface methodology (RSM) experiments. The results indicated that the optimum extraction conditions for the analytes featured a water content of 17%, a liquid/solid ratio of 42 mL g-1 and an extraction time of 30 min. The extracted amounts of liquiritin, isoliquiritin, liquiritigenin, glycyrrhizic acid and isoliquiritigenin reached 5.60, 3.17, 1.27, 74.62 and 1.34 mg g-1, respectively, under optimized conditions, which were much higher than those extracted using conventional organic solvents. In addition, antioxidant tests revealed that the NADES extracts showed higher DPPH and hydroxyl radical-scavenging capacity than the conventional solvent extracts used for comparison. This study provides a suitable approach for efficiently extracting the bioactive compounds of CPLTs. Meanwhile, NADESs can be extended to other natural products as green extraction media.

Antagonistic effect of N-acetyl-L-cysteine against cadmium-induced cytotoxicity and abnormal immune response on chicken peritoneal macrophages.

Cadmium is a highly toxic metal threatening human and animal health. N-acetyl-L-cysteine (NAC) was reported to play a positive role in disease treatment and immune regulation. The present study aimed to explore the effect of NAC administration on Cd-induced cytotoxicity and abnormal immune response on chicken peritoneal macrophages. Peritoneal macrophages isolated from Isa Brown male chickens were exposed to CdCl2 (20 or 50 µM) and/or NAC (500 µM) for different time periods. Results showed that Cd caused dose-dependent damage on chicken peritoneal macrophages characterized by morphologic and ultrastructural alterations, increased cell apoptosis, reactive oxygen species accumulation and mitochondrial injury. Cd exposure inhibited phagocytic activity of chicken peritoneal macrophages, and promoted transcriptional status of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in both unactivated macrophages and cells in response to lipopolysaccharide (LPS) stimuli. Pretreatment with 500 µM NAC did not affect growth of normal chicken peritoneal macrophages, while remarkably inhibiting Cd-caused cell death, oxidative stress, and mitochondrial membrane depolarization. NAC pretreatment significantly prevented intracellular Cd2+ accumulation in the Cd-exposed macrophages. Inhibitory effects of NAC on Cd-induced ROS accumulation and mitochondrial injury on chicken macrophages were confirmed in HD-11 macrophage cell line. In addition, NAC pretreatment promoted the phagocytic activity of Cd-exposed chicken peritoneal macrophages, and significantly inhibited expression of pro-inflammatory factors (IL-1ß, IL-6 and TNF-α) in both Cd-exposed macrophages and Cd-treated cells in response to LPS stimuli. In conclusion, the present study firstly demonstrated the antagonistic effect of NAC against Cd-caused damage and abnormal immune response on chicken peritoneal macrophages. Protective effect of NAC on chicken macrophages was highly related to its suppression on Cd-induced ROS overproduction, pro-inflammatory reaction and intracellular Cd2+ accumulation.

[The role of ZFP580 in the regulation of rat VSMCs migration by ATRA and its mechanism].

OBJECTIVE: To investigate the probable roles of the novel C2H2 zinc finger transcription factor ZFP580 on all-transretinoic acid (ATRA)-regulated VSMCs migration and underlying mechanisms. METHODS: Rat aortic VSMCs were isolated, cultured and identified. VSMCs were treated with ATRA at the concentrations of 0, 5, 10 or 20 µmol/L for 24 hours. The migration ability of VSMCs was observed in each group and compared with control group which was treated by 0 µmol/L ATRA. The mRNA and protein expression levels of ZFP580 were detected by QPCR and Western blot. ZFP580 protein expression in VSMCs was detected under ATRA stimulation when ERK inhibitor PD98059 was used to inhibit the protein expression of ERK. Adenovirus transfection technology was used to obtain VSMCs with overexpression or low expression of ZFP580, and QPCR and Western blot were used to detect the mRNA and protein levels of MMP-2, MMP-9 and ZFP580. RESULTS: On the 10th day of VSMCs culture, immunofluorescence showed that SM22 alpha antibody, as a specific marker of smooth muscle cells, was positive. Compared to the control group, VSMCs migration was reduced by 32%, 43%, and 59% in the group of 5, 10, and 20 µmol/L ATRA pretreatment. Compared with the control group, VSMCs treated by 20 µmol/L ATRA reduced the cell migration by 49%, 36% and 22% at 24, 48 and 72 h. The mRNA and protein expression levels of ZFP580 were increased with the increase of ATRA stimulation solubility and the extension of stimulation time. ERK was increased significantly after 15 min of ATRA stimulation. Pretreatment with ERK inhibitor PD98059 (20 µmol/L) inhibited the expression of ERK protein and reduced the expression of ATRA-induced ZFP580 protein. Overexpression of ZFP580 inhibited the expressions of MMP-2 and MMP-9, whereas down-expression of ZFP580 promoted the expressions of MMP-2 and MMP-9. CONCLUSION: ATRA increased the expression of ZFP580 through the ERK signaling pathway, while ZFP580 was involved in ATRA's inhibition of VSMCs migration by affecting the expression of downstream MMP-2 and MMP-9.

[Differential expression of immediately early gene c-fos in THP-1 macrophage subtype polarization].

Objective: To investigate the expression of immediate early gene c-fos in THP-1 macrophage subtype polarization. Methods: PMA was used to induce the polarization of THP-1 monocytes to macrophages, and the expression of c-fos in the polarization process was observed. After PMA treatment, LPS or IL-4 were used alone to induce the polarization of THP-1 macrophages to the M1 or M2 subtypes. Subsequently, real-time quantitative PCR and western-blot were used to analyze the changes in the expressions of the cell subtype markers CD274, CD86 and CD163. Meanwhile, the expression of c-fos in the polarization process was observed dynamically. Results: The levels of c-fos protein and mRNA expressions were up-regulated during PMA-induced polarization of THP-1 monocytes. The protein and mRNA expressions of c-fos were significantly decreased during the polarization of THP-1 cells into M1 macrophages induced by LPS. The specific markers showed the characteristics of M1 macrophages polarization at 24 h (CD86 protein increased, CD274 and CD163 protein decreased). The protein and mRNA expressions of c-fos were significantly increased during the polarization of THP-1 cells into M2 macrophages induced by IL-4. The specific markers showed the characteristics of M2 macrophages polarization at 24 h (CD86 protein decreased, CD274 and CD163 protein increased). Conclusion: C-fos plays an important role in the polarization of THP-1 monocytes to macrophages. Moreover, it may be involved in the regulation of macrophage subtype polarization, by inhibiting the formation of M1 macrophage and promoting the polarization of macrophages to the M2 subtype.

Effects of Digeda-4 Decoction on the CYP450 Activities in Rats Using a Cocktail Method by HPLC.

Digeda-4 decoction is a traditional Mongolian medicine; its effects on cytochrome (CYP) enzymes are still unclear. CYP450 isoenzymes are the main drug metabolic enzymes, and their activities may be induced or inhibited by certain drugs, which lead to drug interactions in clinical use. Effects of Digeda-4 decoction on the activities of CYP450 subtype enzymes CYP1A2, CYP2C9, CYP2E1, CYP2C19, and CYP3A4 in rats were studied by cocktail method, and the pharmacokinetic parameters of five specific probe drugs (theophylline, tolbutamide, chlorzoxazone, omeprazole, and midazolam) were calculated by DAS software; changes of parameters can be used to evaluate the effects of Digeda-4 decoction on enzyme activities. The experimental rats were divided into three groups: control group, Digeda group, and positive group. Rats in Digeda group were given Digeda-4 decoction through continuous gavage for 14 days. After fasting for 12 hours, the mixed probes drug solution was injected into the tail vein; the blood samples were collected through the orbital vein at different time points. The concentrations of probe drugs in rat plasma were measured by HPLC. Compared with the control group, the half-life time (t1/2) of the pharmacokinetic parameters of theophylline, tolbutamide, omeprazole, and midazolam was prolonged, the area under the curve (AUC) increased, and the plasma clearance (CL) decreased in the Digeda group. Continuous gavage administration for 14 days may inhibit the activities of CYP450 subtype enzymes CYP1A2, CYP2C9, CYP2C19, and CYP3A4 of rats. Herb-drug interaction should be noted between Digeda-4 decoction and the drugs metabolized by CYP1A2, CYP2C9, CYP2C19, and CYP3A4.

[Enhanced Nitrogen Removal of ANAMMOX Treating Saline Wastewater With Betaine Addition].

High salt content could result in the inhibition of microbes and affect biological treatment processes. At present, an important research topic is how to improve the efficiency of biological treatments. The anaerobic ammonia oxidation (ANAMMOX) process was used to treat high saline wastewater. Nitrogen removal performance with betaine was studied by analyzing the ANAMMOX activity, and ammonia nitrogen and nitrate nitrogen removal. The results showed that:① It has obvious improvement when betaine concentration was 0.1-0.4 mmol·L-1. It alleviated the salt stress on bacteria growth inhibition of ANAMMOX, and also promoted the growth of denitrifying bacteria. When betaine concentration was 0.4-0.5 mmol·L-1, denitrifying bacteria was found to have grown greatly. When betaine concentration was greater than 0.5 mmol·L-1, it was unable to alleviate the salt stress inhibiting denitrification efficiency. As a result, betaine concentration of 0.8 mmol·L-1 completely inhibited bacteria. ② When concentration of betaine was 0.3 mmol·L-1, the optimal nitrogen removal efficiency was achieved. NH4+-N and NO2--N increased by 16% and 32%, respectively. Nitrogen removal rate (NRR) increased by 26.8%. ③ At the end of the recovery experiment, with the decreasing concentrations of betaine, NH4+-N was 50.6%, NO2--N was 63.7%, and NRR was 0.65 kg·(m3·d)-1, so the nitrogen removal efficiency underwent fast recovery.

Layer-by-Layer Assembled Conductive Metal-Organic Framework Nanofilms for Room-Temperature Chemiresistive Sensing.

The utility of electronically conductive metal-organic frameworks (EC-MOFs) in high-performance devices has been limited to date by a lack of high-quality thin film. The controllable thin-film fabrication of an EC-MOF, Cu3 (HHTP)2 , (HHTP=2,3,6,7,10,11-hexahydroxytriphenylene), by a spray layer-by-layer liquid-phase epitaxial method is reported. The Cu3 (HHTP)2 thin film can not only be precisely prepared with thickness increment of about 2 nm per growing cycle, but also shows a smooth surface, good crystallinity, and high orientation. The chemiresistor gas sensor based on this high-quality thin film is one of the best room-temperature sensors for NH3 among all reported sensors based on various materials.

[Substrate Inhibition and Kinetic Characteristics of Marine Anaerobic Ammonium Oxidizing Bacteria Treating Saline Wastewater].

An anaerobic sequencing batch reactor (ASBR) was used to study substrate inhibition and kinetic characteristics of marine anaerobic ammonium oxidizing bacteria (MAAOB) treating saline wastewater. The results indicated that when ammonia increased to 1200 mg·L-1, the MAAOB still maintained good nitrogen removal capability, though there was a slight inhibitory effect. At the same time, nitrite nitrogen removal efficiency was stable at about 80.70%. When nitrite increased to 265.6 mg·L-1, the MAAOB were inhibited obviously, and ammonia nitrogen removal efficiency decreased to about 63.01%. When influent nitrite concentration increased to 305.6 mg·L-1, the removal rate of ammonia nitrogen further decreased to 43.93%. The kinetic characteristics resulting from inhibition of the MAAOB were simulated by the Haldane model and Aiba model. Three parameters, TNRRmax, KS, and Ki, and the relationship between effluent substrate concentration and total nitrogen loading (TNRR) were evaluated. Based on further analysis, the Haldane model was more suitable for describing dynamic characteristics resulting from NH4+-N inhibition, while the Aiba model was more suitable for describing the dynamic characteristics resulting from NO2--N inhibition. The predicted effluent inhibitory concentrations of NH4+-N and NO2--N were 3893.625 mg·L-1 and 287.208 mg·L-1, respectively. The results could provide a theoretical basis for saline wastewater treatment by MAAOB.

[Nitrogen Removal Performance of ANAMMOX Process with K+ Addition in Saline Surroundings].

In view of the poor performance of biological nitrogen removal in saline wastewater treatment, nitrogen removal of anaerobic ammonium oxidation(ANAMMOX) with K+ addition was studied. The results showed that K+ addition could strengthen nitrogen removal performance. The effect of K+ on ANAMMOX process was mainly divided into four stages. In the adaptive phase(0-2 mmol·L-1), sudden addition of K+ destroyed the original equilibrium reaction, but ultimately ANAMMOX bacteria could adapt to the presence of K+. Because K+ had no obvious effects on anaerobic ammonia oxidation bacteria, the removal rates of NH4+-N and NO2--N slightly increased. In the ascension phase(2-8 mmol·L-1), K+ played a role in promoting anaerobic ammonia oxidation biological systems, with increasing concentration of K+, the removal rates of NH4+-N and NO2--N significantly increased. In the stabilization phase(8-20 mmol·L-1), the nitrogen removal rate decreased, but was still higher than the control without K+ addition. In the inhibition phase(more than 20 mmol·L-1), K+ largely inhibited anaerobic ammonia oxidation, and its denitrification efficiency was lower than 0 mmol·L-1. In the whole cycle, when the concentration of K+ was 8 mmol·L-1, it achieved the best effect, the average removal rates of NH4+-N and NO2--N were 89.24% and 84.87%, and NRR was 1.113 kg·(m3·d)-1.

[Effect of pH Shock on Nitrogen Removal Performance of Marine Anaerobic Ammonium-Oxidizing Bacteria Treating Saline Wastewater].

The effect of pH shock on nitrogen removal performance of marine anaerobic ammonium-oxidizing bacteria (MAAOB) treating saline wastewater was studied by employing an ASBR reactor. Dynamic characteristics of the MAAOB were simulated by the Andrew model and Ratkowsky model. The results indicated that the reactor had the best nitrogen removal efficiency when the pH value was 7-8. The nitrogen removal rate (NRR) was (0.30±0.04) kg·(m3·d)-1, and the total nitrogen removal efficiency (TNRE) was (76.73±5.74)%. When the pH value was 8.5, FA had a mean concentration of 14.22 mg·L-1 and little effect on nitrogen removal. The NRR was (0.30±0.02) kg·(m3·d)-1. However, NO2--N accumulated and it was not completely removed. When the pH values were 6.5 and 9, the concentrations of FA were 0.22 mg·L-1 and 37.84 mg·L-1, respectively, the NRRs were (0.10±0.02) and (0.15±0.02) kg·(m3·d)-1, and the TNREs were (23.04±9.88)% and (42.12±5.52)%. The tolerance of the MAAOB in alkaline condition was stronger than that in acidic condition. The Andrew model was modified to determine the relationship between NRR and FA. Other parameters such as NRRmax, kS, and kI were also achieved simultaneously. These are key to describing the nitrogen removal process of MAAOB.

[Effect of Temperature on Nitrogen Removal Performance of Marine Anaerobic Ammonium Oxidizing Bacteria].

The effect of temperature on the nitrogen removal performance of marine anaerobic ammonium oxidizing bacteria processing sewage seawater was studied by employing an ASBR reactor, and the dynamic characteristics of the marine anaerobic ammonium oxidizing bacteria at different temperatures were simulated by modified Logistic model. The experimental results indicated that the nitrogen removal performance was affected little at 25-35℃. The total nitrogen removal efficiency (TNRE) remained at (82±2)% and the total nitrogen removal rate (TNRR) was stabilized at (0.62±0.01) kg·(m3·d)-1. When the temperature was 20℃, TNRE increased from 59% at the beginning to 79% after 13 days. This indicated that the marine anammox bacteria still had strong ability of nitrogen removal, and the reactor in the low temperature treatment of sewage containing seawater had a good potential. However, when the temperature dropped to 10-15℃, the nitrogen removal performance of the reactor was inhibited. TNRE decreased to (40±8)% and (11±4)%, respectively. Besides, TNRR also decreased to (0.30±0.04) kg·(m3·d)-1 and (0.08±0.03) kg·(m3·d)-1, respectively. According to the Arrhenius equation, the activation energy for marine anaerobic ammonium oxidation reaction was 26 kJ·mol-1 at 25-35℃, and the activation energy of marine anaerobic ammonium oxidation reaction was 76 kJ·mol-1 at 10-25℃. In addition, dynamic analysis was performed by Logistic model and the NRE and effluent total nitrogen concentration (ceff) at different temperatures were forecasted. The correlation coefficient R2 was between 0.9668 and 0.9957.

[Protection, exploitation and utilization states of specialized Mongolian folk medicine resources and related development strategy].

Mongolian folk medicine resource is the origin of Mongolian medicine development, even more important of which is the specialized Mongolian folk medicine resources with regional and high medicine quality, it processes distinctive national characteristics with irreplaceable important position in traditional Mongolian medicine. Nevertheless, due to the serious destroy of ecological environment and sharp increase of demands, etc. A lot of specialized Mongolian folk medicine resources were endangered, and there still existed some problems in the protection and exploitation and utilization. This paper intends to provide comprehensive insight into the species protection and exploitation and utilization states of specialized Mongolian folk medicine resources. The application and protection status and the existing problems were reviewed, and the development strategies of Mongolian folk medicine resource were analyzed.

Self-assembled dual in-plane gate thin-film transistors gated by nanogranular SiO2 proton conductors for logic applications.

Phosphorus (P)-doped nanogranular SiO(2) films are deposited by plasma-enhanced chemical vapor deposition at room temperature, and a high proton conductivity of ~5.6 × 10(-4) S cm(-1) is measured at room temperature with a relative humidity of 70%. The accumulation of protons at the SiO(2)/indium-zinc-oxide (IZO) interface induces a large electric-double-layer (EDL) capacitance. Thin-film transistors (TFTs) with two in-plane gates are self-assembled on transparent conducting glass substrates. The large EDL capacitance can effectively modulate the IZO channel with a current ON/OFF ratio of >10(7). Such TFTs calculate dual input signals at the gate level coupled with a floating gate, analogous to that of neuron MOS (vMOS). AND logic is demonstrated on the neuron TFTs. Such neuron TFTs gated by P-doped nanogranular SiO(2) shows an effective electrostatic modulation on conductivities of oxide semiconductors, which is meaningful for portable chemical-biological sensing applications.

Artesunate inhibits angiogenesis and downregulates vascular endothelial growth factor expression in chronic myeloid leukemia K562 cells.

Artesunate (ART), a semi-synthetic derivative of artemisinin extracted from the Chinese herb Artemisia annua, is a safe and effective antimalarial drug. In the present investigation, we analyzed the inhibitory effects of ART on angiogenesis and on VEGF production in chronic myeloid leukemia (CML) K562 cells in vitro and in vivo. In order to analyze the effect of ART on VEGF secretion in K562 cells, we examined the level of VEGF secreted in conditioned media (CM) by ELISA assay. The result showed that ART could decrease the VEGF level in CM of K562 cells, even at a lower concentration (2 micromol/l, P<0.01). The inhibitory effect of in vitro angiogenesis was tested on aortic sprouting in fibrin gel. ART could effectively suppress the stimulating angiogenic ability of CM by pretreated with K562 cells for 48 h in a time-dependent manner (days 3-14). The antiangiogenic effect of ART was further evaluated in vivo in chicken chorioallantoic membrane (CAM) neovascularization model. The result indicated that the stimulating angiogenic activity was decreased in response to the K562 cells treated with ART or the CM from K562 cells pretreated with ART in a dose-dependent manner (3-12 micromol/l). Furthermore, we analyzed the level of VEGF expression by western blot and detected the form of VEGF mRNA by RT-PCR in K562 cells. The experiments showed that ART could inhibit the VEGF expression, correlated well with the level of VEGF secreted in CM. These findings suggest that ART might present potential antileukemia effect as a treatment for CML therapy, or as an adjunct to standard chemotherapeutic regimens.

[Association analysis of 30 type 2 diabetes candidate genes in Chinese Han population].

OBJECTIVE: To identify the susceptibility genes of type 2 diabetes in Chinese Han population. METHODS: Single nucleotide polymorphism (SNP) discovery, genotyping and haplotype construction were performed in 30 candidate genes. Case-control study were carried out in a population-based sample and confirmed by the transmission disequilibrium test (TDT) analysis in 77 trio pedigrees. The effects of the SNP rs5210 on gene expression were studied by reporter gene technique. RESULTS: The case-control studies showed that several SNPs on KCNJ11 gene was associated with type 2 diabetes in Chinese Han population, in which the allele frequency of SNP rs5219, the genotype frequency of rs5210, rs2285676 and rs5219, and the frequency of haplotype GA combined of the rs5219 and rs5215 showed significant difference between these two groups (P < 0.05). In addition, TDT test also showed statistical significance on this haplotype GA (P < 0. 05). The reporter gene assay showed that the effect on gene expression was significantly different between two alleles of rs5210 (P < 0.05). CONCLUSION: KCNJII gene is one of the susceptibility genes of type 2 diabetes in Chinese Han population.

[Screening susceptibility genes of type 2 diabetes in Chinese population by single nucleotide polymorphism analysis].

OBJECTIVE: To search for the susceptibility variant (s) of type 2 diabetes in the susceptible regions on chr.1 (1p36.23-36.33, 1q24.3-25.1, and 1q42.12-42.13) by genotyping SNP markers in case-control DNA samples and identifying the haplotype associated with type 2 diabetes. METHODS: Totally 124 SNPs in 33 candidate genes in the mapped regions were chosen from public SNP data or identified by sequencing the samples that were used to search for SNP locus. Sequencing method was used to genotype the loci for 236 sporadic type 2 diabetes patients and 152 normal subjects in Northern Han Chinese population. The haplotypes with significant difference were further analyzed. RESULTS: Of 124 SNPs successfully typed, 4 SNPs that showed association with diabetes status were found: rs203849 (P=0.005, OR=1.60) and rs203826 (P=0.016, OR=1.60) located in sAC gene, rs7535528 (P=0.028, OR=1.45) located in PANK4, rs884363 (P=0.043, OR=1.37) located in CASP9 gene. In addition, the frequencies of two combination types from these 4 SNP genotypes were significantly different between case and control groups (P < 0.001). Furthermore, four haplotypes associated with diabetes were found in haplotype analysis of sAC gene. CONCLUSION: sAC, PANK4, and CA SP9 may be associated with type 2 diabetes in Han population in north China, and it seems that the synergetic effect of these genes is responsible for the development of type 2 diabetes.