Retraction Note: LINC01116 promotes the proliferation and inhibits the apoptosis of gastric cancer cells.

The article "LINC01116 promotes the proliferation and inhibits the apoptosis of gastric cancer cells" by J. Chen, Z.-H. Yuan, X.-H. Hou, M.-H. Shi, R. Jiang, published in Eur Rev Med Pharmacol Sci 2020; 24 (4): 1807-1814-DOI: 10.26355/eurrev_202002_20358-PMID: 32141549 has been retracted by the Editor in Chief. Following the journal's investigation, due to concerns raised regarding non-verifiable nucleotide sequences and cell lines used in the article, the editorial team has contacted the authors to provide a reply regarding the above-mentioned issues. The authors revealed that they suspected errors in the experimental process as early as 2021. After repeated literature reviews and reproducibility experiments, the authors still believe that the paper's conclusions are inaccurate and need further revision. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20358.

Acupuncture improve proteinuria in diabetic kidney disease rats by inhibiting ferroptosis and epithelial-mesenchymal transition.

Objective: To explore the mechanism of acupuncture to relieve diabetic proteinuria in Diabetic Kidney Disease (DKD). Methods: A total of 10 male Sprague-Dawley rats were randomly selected as the negative control group (NC), and a further 30 rats were fed a high-fat diet (HFD) and intraperitoneal streptozotocin (STZ). The DKD model rats in the model group (DKD) and the acupuncture group (DKD + Acu) were randomly assigned. After 4 weeks of intervention, collected urine, peripheral blood, and renal tissues from all rats, and assessed blood urea nitrogen, serum creatinine, triglyceride, 24-h urine protein quantification, and blood glucose, left kidney weight, kidney body ratio index, then observe changes in renal histology in the rats. The renal cortex tissues of three rats from each group were sent for transcriptomic analysis. According to the results of transcriptomic analysis, various kits were used to detect SOD, MDA, GSH, GSH-px, and iron concentration. The expression levels of GPX4 and System Xc-, members of the antioxidative stress pathway, and TfR 1, SLC39A14, FTH 1, and SLC40A1, involved in iron metabolism, in the kidney tissues were measured by western blotting and reverse transcription-quantitative PCR. The expression of mesenchymal phenotype markers and podocyte-specific markers were evaluated by immunofluorescence. Results: Acupuncture promoted the levels of GSH, GSH-px, and SOD, decreased the level of MDA (P < 0.05), promoted the expression of GPX4 and System Xc- (P < 0.05), decreased the expression of TfR1 and SLC39A14 (P < 0.01), and increased the expression of FTH 1 and SLC40A1 (P < 0.05), inhibited the expression of TGF-ß1, desmin, FSP-1, and α-SMA (P < 0.05), promoted the expression of Nephrin, Podocin, and CD2AP (P < 0.05). Conclusion: Improving the ability of podocytes to prevent oxidative stress and restoring iron ion homeostasis, can improve Ferroptosis and block epithelial-mesenchymal transition, improve podocyte injury, restore filtration function, and reduce proteinuria in DKD rats.

Integrating transcriptome and metabolome to identify key genes regulating important muscular flavour precursors in sheep.

Flavour precursors are the basis of meat flavour, and their metabolism is regulated by a variety of enzymes. Thus, it is of great significance to identify the key genes related to meat flavour precursors. In this study, the difference in flavour precursors and transcriptome between Hu sheep and Dorper with different intramuscular fat (IMF) content were investigated using widely targeted metabolomics and RNA-sequencing technologies. Then, the key genes regulating the metabolism of vital precursors were explored by integrating transcriptome and metabolome. Consequently, 594 metabolites were detected in sheep longissimus dorsi, and 76 differentially abundant metabolites (DAMs) were identified between Hu sheep and Dorper. No DAMs were observed between distinct IMF content groups within each breed. A total of 10 lysophospholipids (LPs), including four lysophospholipid ethanolamines and six lysophospholipid cholines, were identified as the main differential precursors between Hu sheep and Dorper. Furthermore, the weighted gene coexpression network analysis uncovered three differentially coexpression modules that were significantly associated with the content of differential LPs in Dorper. From the three modules, GLB1, PLD3, LPCAT2, DGKE, ACOT7, and CH25H genes were identified as key genes regulating the metabolism of LPs. This work provides an insight into understanding the difference in flavour between different sheep breeds, as well as a basis for further exploring the regulatory mechanism of key genes on LPs.

NLRP3 rs1539019 is significantly associated with chronic obstructive pulmonary disease in a Chinese Han population: a case-control study.

OBJECTIVE: COPD is a complex respiratory disease characterized by chronic airway inflammation and the airflow limitations are not fully reversible due to the combination of genetic and environmental factors. Genetic factors such as polymorphisms, may affect the susceptibility of COPD. In the present study, we examined the association between the polymorphisms of three genes and COPD risk in a Chinese Han population. PATIENTS AND METHODS: A total of 375 COPD patients and 284 control subjects were recruited from November 2018 to June 2021. Data on demographic basic information, smoking status, history of coal dust exposure, and peripheral blood were collected from subjects of two groups. Three polymorphisms (NLRP3 rs1539019, LAMB1 rs4320486,  IL-6 rs1800796) were analyzed. Logistic analysis was used to evaluate the genetic contribution of selected SNPs to COPD susceptibility. RESULTS: The AC genotype of NLRP3 rs1539019 significantly decreased COPD risk compared with CC genotype (adjusted OR = 0.508, 95% CI 0.336-0.767). In the stratification analyses, the AC genotype significantly decreased the risk of COPD in subjects aged 60 and over (p=0.005; adjusted OR = 0.553; 95% CI 0.366-0.835) with current smoking status (p=0.002; adjusted OR = 0.419; 95% CI 0.240-0.732) when compared with AA+CC genotype. Moreover, a significantly decreased risk for GOLD III COPD was found in genotype AC of NLRP3 rs1539019 (p=0.006; adjusted OR = 0.502; 95% CI 0.306-0.822). CONCLUSIONS: Our present study revealed that the genotype AC of NLRP3 rs1539019 is related to a decreased risk of COPD in a Chinese Han population, a large-sample, multi-center, multi-ethnic study is needed to further confirm our study.

Clinical outcomes in patients with infrapopliteal arterial occlusive disease treated by lower extremity bypass surgery: a comparison of atherosclerosis and thromboangiitis obliterans.

OBJECTIVE: Surgical bypasses are commonly utilized for the treatment of infrapopliteal arterial occlusive disease resulting from atherosclerosis (ASO) and thromboangiitis obliterans (TAO), especially when endovascular procedures fail. The aim of this study is to compare the in-hospital and follow-up outcomes of ASO and TAO patients treated with infrapopliteal bypass surgery. PATIENTS AND METHODS: A total of 32 infrapopliteal bypasses were analyzed in 18 TAO patients and 14 ASO patients. Preoperative and postoperative arterial Doppler ultrasonography was performed in all patients. The ankle-brachial index (ABI) was calculated preoperatively and postoperatively in all cases. All patients were followed-up for at least one year and clinical outcomes were recorded. RESULTS: Within 1-7 days postoperatively, 4 grafts in TAO patients occluded; nevertheless, 1 graft occlusion occurred in ASO patients. Patency rates at in-hospital were 77.8% and 92.9% in TAO and ASO patients, respectively. In 27 patients with successful infrapopliteal bypass, ABIs and crural peak arterial flow velocities significantly increased at 1-7 days postoperatively. During the period of follow-up, 6 graft occlusions occurred in TAO patients, and one ASO patient died of myocardial infarction. Patency rates at follow-up were 44.5% and 85.7% in TAO and ASO patients. For TAO patients with graft failure, ABIs at follow-up did not statistically differ from those postoperatively; however, they were significantly higher than those preoperatively. CONCLUSIONS: Infrapopliteal bypass surgery is a feasible and effective procedure for ASO and TAO patients. Patency rates are lower in TAO than those in ASO during the in-hospital and follow-up period. However, TAO patients had the ischemic symptom relief and the improvement in ABI despite graft occlusion one year postoperatively.

[Clinical cure strategies for hepatitis B: direct-acting antiviral drugs].

Direct-acting antivirals (DAAs) play a critical role for the therapy of chronical hepatitis B. DAAs can decrease the production of viral progeny of hepatitis B virus (HBV), breaking the viral dynamic equilibrium between: (1) virion production from hepatocytes and clearance from circulation; (2) replenishment and decay of covalently closed circular (ccc)DNA pool inside infected hepatocytes. Nucleos(t)ide analogues can potently shift the first balance to undetectable viremia in the blood, but have limited or no effect on the second one, thus making it imperative to develop new agents targeting additional step(s) of HBV life cycle. We herein briefly introduce the DAAs currently in development by classifying them as agents affecting the replenishment or the decay of cccDNA pool.

Low expression of CircRNA HIPK3 promotes osteoarthritis chondrocyte apoptosis by serving as a sponge of miR-124 to regulate SOX8.

OBJECTIVE: CircRNA, a type of circular RNA, has recently been shown to be a potential target for osteoarthritis (OA). Circular RNA HIPK3 (CircHIPK3) is reported to be abnormally expressed in various disease tissues and affects the occurrence and development of the disease. However, the role and underlying mechanism of CircRNA HIPK3 in osteoarthritis are still unclear. The purpose of this study is to explore the effect of CircRNA HIPK3 on osteoarthritis and analyze its regulatory mechanism. PATIENTS AND METHODS: We took human OA tissues, normal knee cartilage, human OA chondrocytes and normal chondrocytes as the research objects. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect CircHIPK3 expression level, its target gene miRNA 124 (miR-124) and downstream target molecule SOX8. Flow cytometry analysis was applied to discover the apoptosis of CircHIPK3 and miR-124 on OA cartilage in different transfection situations. Moreover, Western blot and RT-qPCR were used to detect the expression of caspase-3 in OA chondrocytes. The binding site of CircRNA HIPK3 and miR-124, miR-124, and SOX8 were verified by using Dual-Luciferase assay. RESULTS: High expressed CircHIPK3 and low expressed miR-124 were found in OA tissues and OA chondrocytes. In addition, the Dual-Luciferase report showed CircHIPK3 acted as a sponge of miR-124 in OA chondrocytes. CircHIPK3 and miR-124 expression in OA tissue were confirmed to be negatively correlated. To our surprise, knocking down CircHIPK3 and transfected miR-124 mimics both inhibited the apoptosis of OA chondrocytes. Further experiments verified that the downstream target molecule of miR-124 was SOX8 in OA chondrocytes. Besides, miR-124 inhibitors reversed the knockdown of CircHIPK3 while si-SOX8 reversed the miR-124 inhibitors effect of apoptosis on OA chondrocytes. CONCLUSIONS: Our results demonstrated that CircHIPK3 was significantly upregulated in OA cartilage tissue and cells. Low expression of CircHIPK3 promoted the apoptosis of OA chondrocytes by promoting miR-124 to suppress SOX8 expression. The molecular mechanism of CircHIPK3 in present study is expected to provide new ideas for the treatment of osteoarthritis.

Effects of induced stress from the live LaSota Newcastle disease vaccination on the growth performance and immune function in broiler chickens.

This study was conducted to assess the growth performance and immunological effects of vaccination-induced stress on broilers. The chickens were administered 0, 2, 4, 8, and 16 doses of live LaSota Newcastle disease (ND) vaccine and slaughtered on the 1st, 7th, 14th, and 21st day post vaccination. The results showed that the serum antibody titers after Newcastle disease virus (NDV) vaccination were elevated at day 7 post vaccination, peaked at day 14, then declined by day 21. Interestingly, the antibody titers peaked at 2 doses, and no further dose-dependent titer increases were observed. This study demonstrated that vaccination-induced stress increased serum adrenocorticotropic hormone and cortisol, affected growth performance (average daily gain, average daily feed intake, and feed conversion ratio), and triggered apoptosis in spleen lymphocytes by downregulating the ratio of Bcl-2 to BAX and upregulating the gene expressions of caspase-3 and -9, which was concordant with the activation of the enzymatic activities of caspase-3 and -9. This study suggests that NDV vaccine doses in broilers must be controlled judiciously because increasing the number of doses resulted in increased lymphocyte apoptosis while the peak of the antibody titer and optimal growth performance were achieved at a low number of doses (2 doses).

LINC01116 promotes the proliferation and inhibits the apoptosis of gastric cancer cells.

OBJECTIVE: To detect the relative expression of long intergenic non-protein coding ribonucleic acid (LINC) 01116 in gastric cancer (GC) tissues and cells and analyze the correlations of LINC01116 expression with the clinicopathologic characteristics of patients and investigate the biological functions of LINC01116 via in vitro experiments. PATIENTS AND METHODS: The quantitative Real Time Fluorescence-Polymerase Chain Reaction (qRT-PCR) was applied to detect the relative expression level of LINC01116 in 73 cases of tissues and cells in GC patients. The patients were divided into LINC01116 high expression group and LINC01116 low expression group, and the correlations of LINC01116 with patient's pathological characteristics were statistically analyzed. In vitro experiments [cell counting kit-8 (CCK-8) assay, colony formation assay, and flow cytometry] were adopted to investigate the influences of LINC01116 on the biological functions of GC cells. RESULTS: According to the results of qRT-PCR, the expression of LINC01116 was upregulated in 54 out of 73 cases of tissues (fold change >1), and it was upregulated in GC cells compared with that in the normal gastric mucosal epithelial cells (GES-1). The statistical analysis manifested that the highly expressed LINC01116 was positively correlated with the tumor-node-metastasis (TNM) stage (p=0.008), lymph node metastasis (p=0.005), and depth of invasion (p=0.007) of the GC patients. The patients with high expression of LINC01116 in the GC tissues had a shorter survival time than those with low expression (p=0.017). After interference in the expression of LINC01116, it was shown in CCK-8 assay and colony formation assay that the proliferative capacity of the cells was decreased. The results of flow cytometry indicated that the cell cycle was arrested at the G1/G0 phase, and the apoptosis rate was increased. CONCLUSIONS: LINC01116 is highly expressed in GC tissues and cells, and highly expressed LINC01116 indicates poor prognosis of the patients, promotes the proliferation, and inhibits the apoptosis of GC cells.

Long non-coding RNA SOX21-AS1 promotes cell proliferation and invasion through upregulating PAK7 expression by sponging miR-144-3p in glioma cells.

In this study, the function of long non-coding RNA SOX21 antisense RNA 1 (SOX21-AS1) in the progress of glioma was explored. RNA and protein levels were measured via quantitative reverse transcription-PCR (qRT-PCR) and western blot analysis. In addition, we examined cell proliferation, apoptosis, migration and invasion. The interaction between SOX21-AS1 (PAK7) and miR-144-3p was determined via RNA immunoprecipitation (RIP) assay and Luciferase reporter assay. SOX21-AS1 was upregulated in glioma tissues and cells. SOX21-AS1 knockdown was carried out in glioma cells (U251 and U87 cells). Moreover, in vitro, SOX21-AS1 knockdown repressed proliferation, migration, invasion and enhanced apoptosis in glioma cells. In vivo, SOX21-AS1 knockdown suppressed tumor growth in mice. In addition, SOX21-AS1 could sponge miR-144-3p, which was determined to bind to PAK7. miR-144-3p knockdown promoted proliferation, migration, invasion and inhibited cell apoptosis. Importantly, the effects of SOX21-AS1 knockdown-induced proliferation, migration, invasion, and apoptosis were alleviated in glioma cells co-transfected with SOX21-AS1 and miR-144-3p knockdown. Furthermore, miR-144-3p knockdown also attenuated Wnt/ß-catenin pathway-associated protein levels induced by SOX21-AS1 knockdown. These results indicated that SOX21-AS1/miR-144-3p/PAK7 axis played an oncogenic role in glioma cells by regulating Wnt/ß-catenin pathway, which suggests a rational therapeutic strategy for glioma.

Dietary exposure assessment of cyadox based on tissue depletion of cyadox and its major metabolites in pigs, chickens, and carp.

The tissue kinetics of cyadox, an antibacterial agent used in food animals, and its major metabolites in pigs, chickens, and carp were investigated followed by a complete dietary exposure assessment to evaluate the food safety of cyadox. Cyadox and its major metabolites, bisdeoxycyadox (Cy1), 4-desoxycyadox (Cy2), N-(quinoxaline-2-methyl)-cyanide acetyl hydrazine (Cy4), quinoxaline-2-carboxylic acid (Cy6), and 2-hydromethyl-3-hydroxy-quinoxaline (Cy12), were simultaneously quantitated with a high-performance liquid chromatography-ultraviolet (HPLC-UV) method. Pigs, chickens, and carp were fed with 150 mg/kg cyadox in feed for consecutive 60, 40, and 30 days, respectively. The residue amount of cyadox and its major metabolites in liver, kidney, muscle, and fat (skin) tissues was determined. Cy2 was below the limit of quantitation even at the withdrawal time of 6 hr, cyadox, Cy4, Cy6, and Cy12 could be detected at 6-24 hr with low level less than 50 µg/kg. By contrast, Cy1 persisted for 3 days in the kidney of pigs and chickens, and in the liver of carp. Based on these residue depletion data and previous toxicology results, the global estimated chronic dietary exposure assessment of cyadox for general population was conducted, indicating a zero withdrawal time (WDT) may be appropriate for cyadox in food animals when used in feed for prolonged administration. These results provide analytical techniques and safety standards suitable for residue monitoring of cyadox in food animals.

Effect of Vanadium and Tea Polyphenols on Intestinal Morphology, Microflora and Short-Chain Fatty Acid Profile of Laying Hens.

Vanadium (V) is a trace element which can induce dysfunction of gastro-intestine and egg quality deterioration of laying hens. This study was conducted to determine the effect of tea polyphenols (TP) on intestinal morphology, microflora, and short-chain fatty acid (SCFA) profile of laying hens fed vanadium containing diets. A total of 120 Lohman laying hens (67-week-old) were randomly divided into 4 groups with 6 replicates and 5 birds each for a 35-day feeding trial. The dietary treatments were as follows: (1) control (CON), fed a basal diet; (2) vanadium treatment (V10), CON +10 mg V/kg; (3) TP treatment 1 (TP1): V10 + 600 mg TP/kg; (4) TP treatment 2 (TP2): V10 + 1000 mg TP/kg. Fed 10 mg V/kg diets to laying hens did not affect the cecum flora diversity index (H), degree of homogeneity (EH), and richness (S), but hens fed TP2 diet decreased the H, EH, and S (P < 0.05). The cecum butyrate acid concentration was lower in V10 treatment and higher in TP2 treatment (P < 0.05). Addition of 10 mg/kg V resulted in an increased (P < 0.01) duodenal cell apoptosis rate, and 1000 mg/kg TP supplementation overcame (P < 0.01) this reduction effect induced by vanadium. The results indicated that supplementation of 10 mg/kg vanadium increased duodenal cell apoptosis and reduced cecum butyrate acid content. Addition of 1000 mg/kg TP increased the SCFA production to affect cecum flora ecology and protected the duodenal cell from excess apoptosis caused by vanadium.

Effect of tea polyphenols on production performance, egg quality, and hepatic antioxidant status of laying hens in vanadium-containing diets.

This study was conducted to determine the effect of tea polyphenols (TP) on production performance, egg quality, and hepatic-antioxidant status of laying hens in vanadium-containing diets. A total of 300 Lohman laying hens (67 wk old) were used in a 1 plus 3 × 3 experiment design in which hens were given either a diet without vanadium and TP supplementation (control) or diets supplemented with 5, 10, or 15 mg V/kg and TP (0, 600, 1,000 mg/kg) diets for 8 wk, which included 2 phases: a 5-wk accumulation phase and a 3-wk depletion phase. During the accumulation phase, dietary vanadium addition decreased (linear, P < 0.01) albumen height and Haugh unit (HU), and TP supplementation mitigated (linear effect, P < 0.01) this reduction effect induced by vanadium. Eggshell thickness (linear, P < 0.01), redness (linear and quadratic, P < 0.05), and yellowness (linear and quadratic, P < 0.05) were decreased by vanadium and increased by the effect of TP when a vanadium-containing diet was fed. In the depletion phase, the bleaching effect on eggshells induced by vanadium disappeared one wk after vanadium withdrawal. Eggshell thickness, eggshell strength, albumen height, and HU were lower (P < 0.05) in the 15 mg/kg vanadium group compared with the control diet until 2 wk post vanadium challenge, but hens fed 15 mg/kg vanadium and 600 mg/kg TP showed no difference from the control diet only after 1 wk withdrawal. In the liver, the activity of glutathione S-transferases and glutathione peroxidase was increased (linear, P < 0.01) with the TP addition at 5 wk in the accumulation phase in the vanadium-containing diet; the malondialdehyde content increased (linear effect, P = 0.02) with the addition of vanadium. The results indicate that supplementation of 10 and 15 mg/kg vanadium resulted in reduced albumen quality, bleaching effect on eggshell color, and antioxidant stress in the liver. The effect of TP addition can prevent laying hens from the adverse effect of vanadium on egg quality, liver antioxidant stress and shorten the recovery time.

Effect of temperature change on power generation of microbial fuel cell.

Microbial fuel cell (MFC), which can directly generate electricity from biodegradable materials, has been receiving increasing attention. Effects of temperature change on power density, electrode potential, columbic efficiency, chemical oxygen demand removal and internal resistance in two chambers MFCs were examined in this paper. The maximum power density of 7.89 W/m3 was achieved at 37 degrees C, with 199% higher at 10 degrees C (2.64 W/m3), 24% higher at 30 degrees C (6.34 W/m3) and 21% higher at 43 degrees C, no steady power generation was observed at 55 degrees C. Low temperature to 10 degrees C might have a huge effect on anode potential, especially at higher current, but increasing the temperature to 43 degrees C had a main effect on the cathode performance when the MFCs have been established at 37 degrees C. The internal resistance of MFC was about 29 omega at 37 degrees C, and increased 62% and 303% when MFC switched to 30 degrees C and 10 degrees C. Similarly, internal resistance increased 48% at 43 degrees C. The effect of temperature on MFC performance was expressed by internal resistance, the higher the internal resistance of MFC, the lesser the power density obtained. The Columbic efficiencies were 8.65% at 30 degrees C, 8.53% at 37 degrees C, and 13.24% at 43 degrees C. These results demonstrate that MFCs can effectively be operated over a wide range of temperatures.

Increased numbers of T helper 17 cells and the correlation with clinicopathological characteristics in multiple myeloma.

OBJECTIVE: T helper 17 (Th17) cells play important roles in adaptive immunity and are involved in several inflammatory and autoimmune diseases, but little is known about their role in tumour immunity. The current study investigated the involvement of Th17 cells in multiple myeloma. METHODS: Flow cytometry was used to investigate the frequencies of Th17 cells in peripheral blood mononuclear cells from 30 patients with multiple myeloma and from 14 healthy control subjects. The concentrations of Th17-associated cytokines (interleukin [IL]-6, IL-17, IL-1ß and IL-23) were measured by enzyme-linked immunosorbent assay. RESULTS: There was a significantly increased proportion of Th17 cells, and increased plasma concentrations of Th17-associated cytokines, in patients with multiple myeloma compared with healthy controls. There was a significant relationship between the proportion of Th17 cells and clinical tumour stage, serum lactate dehydrogenase concentration and serum creatinine concentration. CONCLUSIONS: Th17 cells might be important therapeutic targets in multiple myeloma and could facilitate a better outcome for tumour immunotherapy.

Pharmacokinetics of tulathromycin and its metabolite in swine administered with an intravenous bolus injection and a single gavage.

Tulathromycin is a macrolide antimicrobial agent proposed for therapeutic use in treatment of porcine and bovine respiratory disease. In this study, the absolute bioavailability of tulathromycin solution was investigated in pigs. Eight pigs, with body weight of 20.5 ± 1.6 kg, were given a single dose of tulathromycin at 2.5 mg/kg oral (p.o.) and intravenous (i.v.) in a crossover design. The plasma concentrations of tulathromycin and its metabolite were determined by LC-MS/MS method, and the pharmacokinetic parameters of tulathromycin were calculated by noncompartmental analysis. After p.o. administration, the maximum plasma concentration (C(max) ) was 0.20 ± 0.05 µg/mL at 3.75 ± 0.71 h. The terminal half-life (t(1/2λz) ) in plasma was 78.7 ± 6.75 h, and plasma clearance (Cl/F) was 1.14 ± 0.28 L/h/kg. After i.v. injection, plasma clearance (Cl) was 0.580 ± 0.170 L/h/kg, the volume of distribution (Vz) was 64.3 ± 21.2 L/kg, and the t(1/2λz) was 76.5 ± 13.4 h. In conclusion, an analytical method for the quantification of tulathromycin and its metabolite in plasma in swine was developed and validated. Following p.o. administration to pigs at 2.5 mg/kg b.w., tulathromycin was rapidly absorbed and the systemic bioavailability was 51.1 ± 10.2.

Inhibition of cytochrome P450 2A participating in coumarin 7-hydroxylation in pig liver microsomes.

Five commonly used human cytochrome P450 (CYP) inhibitors were examined for their effects on coumarin 7-hydroxylase (CYP2A) activity in pig liver microsomes. The K(m) and V(max) values for coumarin 7-hydroxylation in pig liver microsomes were estimated to be 1 µm and 0.26 nmol·mg/min, respectively. The following human CYP inhibitors caused little or no inhibition of CYP2A as defined by a K(i) > 200 µm: quinidine (CYP2D6), troleandomycin (CYP3A4), and sulfaphenazole (CYP2C9). The other two human CYP inhibitors were classified as strong inhibitors of CYP2A: 8-methoxypsoralen (CYP2A6) and α-naphthoflavone (CYP1A1/2). In the absence of a preincubation period, 8-MOP inhibited the 7-hydroxylation of coumarin with a K(i) value of 1.1 µm, which decreased to 0.1 µm when 8-MOP was preincubated with pig liver microsomes for 3 min. α-Naphthoflavone inhibited the 7-hydroxylation of coumarin with a K(i) value of 32 µm, which did not increase ability to inhibitor CYP2A when α-naphthoflavone was preincubated with pig liver microsomes for 3 min. These results of this study suggest that 8-MOP is a potent, mechanism-based inhibitor of pig CYP2A activity in pig liver microsomes.

Analytical determination and pharmacokinetics of major metabolites of carbasalate calcium in broilers following oral administration.

As a newer anti-inflammatory agent, carbasalate calcium is used in various animal species. In this study, the pharmacokinetics of carbasalate calcium was investigated in broilers. Broilers, with body weight of 2.0 ± 0.3 kg, were administrated carbasalate calcium soluble powder at a single dose of 40 mg/kg body weight orally. The plasma concentrations of its metabolites, aspirin (ASA), salicylic acid (SA) and gentisic acid (GA) were determined by LC-MS/MS method and the pharmacokinetic parameters were calculated by noncompartmental analysis. After oral administration of carbasalate calcium, the plasma drug concentration for ASA, SA and GA reached a peak (C(max) ) of 8.88 ± 1.31, 42.6 ± 4.62 and 10.1 ± 2.16 µg/mL at 0.170, 2.00 and 2.00 h, respectively. The terminal half-life (t(1/2λz) ) of ASA, SA and GA was 11.2 ± 8.04, 23.7 ± 17.1 and 28.6 ± 4.90 h, respectively. In conclusion, analytical method for the quantification of ASA, SA and GA in plasma in the broilers was developed and validated. In broilers, carbasalate calcium is quickly metabolized in ASA and ASA is rapidly converted to SA and one of the metabolites of SA is GA.

A meta-analysis of the efficacy and safety of recombinant activated factor VII for patients with acute intracerebral hemorrhage without hemophilia.

Hematoma growth is common in intracerebral hemorrhage (ICH) and is associated with a poor outcome for patients. To evaluate the efficacy and safety of recombinant activated factor VII (rFVIIa) used as a hemostatic agent in patients with ICH without hemophilia, we searched Medline, Scopus, the Cochrane Library, Clinicaltrials.gov and the Stroke Trials Directory. Five randomized controlled trials were selected for analysis. Although rFVIIa can reduce the change in ICH volume, there was no significant difference in mortality, modified Rankin Scale (mRS) score or extended Glasgow Outcome Scale (GOS-E) score in patients treated with rFVIIa or placebo. There was a significant increase in arterial thromboembolic adverse events (TAE) in patients treated with rFVIIa. There was an increase in deep vein thrombosis in patients with spontaneous ICH and traumatic ICH. In conclusion, the use of rFVIIa reduces the growth of the hematoma but does not improve patient survival or functional outcome after ICH; in addition, rFVIIa increases the incidence of arterial TAE.

Primary molecular features of self-incompatible and self-compatible F(1) seedling from apricot (Prunus armeniaca L.) Katy x Xinshiji.

Expression of the S-RNase genes in the self-compatible (SC) apricot (Prunus armeniaca L.) cultivar Katy, the self-incompatible (SI) cultivar Xinshiji and their F(1) seedling was examined in this study. Three S-genotypes, S(9)Sc (Sc, self-compatibility S-gene absent from the style), S(8)S(9), and S(8)S(10), were obtained. Seedlings with S-RNase that migrated as a single band in gel electrophoresis were SC, despite high transcript abundance, and those with S-RNase that migrated as two bands were SI with high transcript abundance or SC with low transcript expression. S(8)-RNase was induced in SI cultivars only 24 h after self-pollination, indicating post-transcriptional regulation of S(8)-RNase in SI apricots. A Proteomic study showed that 35 protein spots were synthesized differently between SC and SI pistils. Fifteen of the 35 protein spots were identified; nine proteins, including receptor protein kinase-like protein, reversibly glycosylated polypeptide-2, and isoflavone reductase-like protein, were detected only in the SC pistils; while nine proteins, including actin 7, a putative serine/threonine kinase, and S-RNase, were detected only in the SI pistils. A mitochondrial NAD-dependent malate dehydrogenase and a probable elongation factor G were up-regulated, while heat shock cognate 70 was down-regulated in the SC pistils compared to those in the SI pistils. The results suggest that the proteins responsible for self-compatibility and self-incompatibility may be different.