Conjugated linoleic acid (CLA) as a functional food: Is it beneficial or not?

Conjugated linoleic acid (CLA) has attracted great attention in recent years as a popular class of functional food that is broadly used. It refers to a group of geometric and positional isomers of linoleic acid (LA) with a conjugated double bond. The main natural sources of CLA are dairy products, beef and lamb, whereas only trace amounts occur naturally in plant lipids. CLA has been shown to improve various health issues, having effects on obesity, inflammatory, anti-carcinogenicity, atherogenicity, immunomodulation, and osteosynthesis. Also, compared to studies on humans, many animal researches reveal more positive benefits on health. CLA represents a nutritional avenue to improve lifestyle diseases and metabolic syndrome. Most of these effects are attributed to the two major CLA isomers [conjugated linoleic acid cis-9,trans-11 isomer (c9,t11), and conjugated linoleic acid trans-10,cis-12 isomer (t10,c12)], and their mixture (CLA mix). In contrast, adverse effects of CLA have been also reported, such as glucose homeostasis, insulin resistance, hepatic steatosis and induction of colon carcinogenesis in humans, as well as milk fat inhibition in ruminants, lowering chicken productivity, influencing egg quality and altering growth performance in fish. This review article aims to discuss the health benefits of CLA as a nutraceutical supplement and highlight the possible mechanisms of action that may contribute to its outcome. It also outlines the feasible adverse effects of CLA besides summarizing the recent peer-reviewed publications on CLA to ensure its efficacy and safety for proper application in humans.

Pharmacokinetic and Pharmacodynamic Drug-Drug Interactions: Research Methods and Applications.

Because of the high research and development cost of new drugs, the long development process of new drugs, and the high failure rate at later stages, combining past drugs has gradually become a more economical and attractive alternative. However, the ensuing problem of drug-drug interactions (DDIs) urgently need to be solved, and combination has attracted a lot of attention from pharmaceutical researchers. At present, DDI is often evaluated and investigated from two perspectives: pharmacodynamics and pharmacokinetics. However, in some special cases, DDI cannot be accurately evaluated from a single perspective. Therefore, this review describes and compares the current DDI evaluation methods based on two aspects: pharmacokinetic interaction and pharmacodynamic interaction. The methods summarized in this paper mainly include probe drug cocktail methods, liver microsome and hepatocyte models, static models, physiologically based pharmacokinetic models, machine learning models, in vivo comparative efficacy studies, and in vitro static and dynamic tests. This review aims to serve as a useful guide for interested researchers to promote more scientific accuracy and clinical practical use of DDI studies.

CEACAM1 as a molecular target in oral cancer.

OBJECTIVE: The majority of oral cancer is caused by malignant transformation of squamous cells in surface of the oral mucosa. However, the relationship between CEACAM1 and oral cancer is unclear. METHODS: GSE23558 and GSE25099 profiles were downloaded from gene expression omnibus (GEO). Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. Construction and analysis of protein-protein interaction (PPI) Network. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG), gene set enrichment analysis (GSEA), gene expression heatmap, immune infiltration analysis, comparative toxicogenomics database (CTD) were performed. TargetScan screened miRNAs that regulated central DEGs. Western blotting (WB) experiment was performed. RESULTS: 1269 DEGs were identified. According to GO analysis, they were mainly enriched in same protein binding, signal receptor binding, cell surface, epithelial cell development. KEGG analysis showed that they were mainly enriched in cancer pathways, PI3K Akt signaling pathway, TNF signaling pathway, NF kappa B signaling pathway, TGF beta signaling pathway. PPI network showed that 11 genes (CDCA8, CCNA2, MELK, KIF2C, CDC45, HMMR, TPX2, CENPF, CDK1, CEP55, CEACAM1) were obtained. Gene expression heatmap showed that CEP55 and MELK were highly expressed in oral cancer samples. CEACAM1 was lowly expressed in oral cancer samples. CEACAM1, CEP55 and MELK were involved in tumor, inflammation, necrosis, and proliferation. Western blotting (WB) showed that CEACAM1 in oral cancer samples was lower than that in normal samples, after CEACAM1 knockdown, it was lower than that in oral cancer samples. CONCLUSION: CEACAM1 is lowly expressed in oral cancer, the lower CEACAM1, the worse prognosis.

A physiologically based pharmacokinetic model to optimize the dosage regimen and withdrawal time of cefquinome in pigs.

Cefquinome is widely used to treat respiratory tract diseases of swine. While extra-label dosages of cefquinome could improve clinical efficacy, they might lead to excessively high residues in animal-derived food. In this study, a physiologically based pharmacokinetic (PBPK) model was calibrated based on the published data and a microdialysis experiment to assess the dosage efficiency and food safety. For the microdialysis experiment, in vitro/in vivo relative recovery and concentration-time curves of cefquinome in the lung interstitium were investigated. This PBPK model is available to predict the drug concentrations in the muscle, kidney, liver, plasma, and lung interstitial fluid. Concentration-time curves of 1000 virtual animals in different tissues were simulated by applying sensitivity and Monte Carlo analyses. By integrating pharmacokinetic/pharmacodynamic target parameters, cefquinome delivered at 3-5 mg/kg twice daily is advised for the effective control of respiratory tract infections of nursery pig, which the bodyweight is around 25 kg. Based on the predicted cefquinome concentrations in edible tissues, the withdrawal interval is 2 and 3 days for label and the extra-label doses, respectively. This study provides a useful tool to optimize the dosage regimen of cefquinome against respiratory tract infections and predicts the concentration of cefquinome residues in edible tissues. This information would be helpful to improve the food safety and guide rational drug usage.

Prognostic risk factors for patients with hepatic sinusoidal obstruction syndrome caused by pyrrolizidine alkaloids.

Pyrrolizidine alkaloids induced hepatic sinusoidal obstruction syndrome (PA-HSOS) often occurs after consuming herbs or a dietary supplement containing the plant Tu-San-Qi. Limited data exists to identify patients with fatal outcomes for early interventions. We aimed to analyze the predictors for 3-month survival. We retrospectively enrolled PA-HSOS patients in 5 hospitals and extracted data from the onset of PA-HSOS to 36 months. Outcome measurements were 3-month and 36-month survival rates, baseline prognostic predictors for survival, and the effects of anticoagulant therapy. Among 49 enrollees, the median age was 60 and 49% male. At the onset of PA-HSOS, patients with Child-Turcotte-Pugh (CTP) class of A, B, or C were 8.2% (4/49), 42.8% (21/49) and 49.0% (24/49), respectively. None of them received a transjugular intrahepatic portosystemic shunt or a liver transplant. The 3-month and 36-month survival rates were 86% and 76%, respectively. Compared to the CTP class A or B, class C at baseline independently predicted lower survival rates at both 3 and 36 months. However, anticoagulation therapy treatment within the first 3 months independently predicted significantly higher survival rates at both time points. CTP class C and anticoagulant therapy were the independent predictors for short-term and long-term survival. Anticoagulant therapy could decrease mortality rate of CTP class C patients. The greatest benefit of anticoagulant evaluated by 3-month survival rate was in patients with CTP class C compared with those without treatment (93% vs 40%, P = .009). There were no bleeding complications reported in patients treated with the anticoagulant.

Three dimensional cyclic trinuclear units based metal-covalent organic frameworks for electrochemical CO2RR.

A three-dimensional metal-covalent organic framework (3D-MCOF) based on cyclic trinuclear units was synthesized using organic tetrahedral linkers and copper-based cyclic trinuclear complexes. The novel type of 3D-MCOF, named 3D-CTU-MCOF, with the ctn topology, is reported herein for the first time. Our study demonstrated enhanced electrocatalytic capacity for CO2 reduction reaction of 3D-CTU-MCOF compared to independent cyclic trinuclear units.

Metabolism and Tissue Elimination of Diaveridine in Swine, Chickens, and Rats Using Radioactive Tracing Coupled with LC-ESI-IT-TOF/MS.

Diaveridine (DVD) has widespread use in food animals due to its antibacterial synergistic effects. This study revealed the metabolism, excretion, and tissue elimination of DVD in swine, chickens, and rats following oral gavage of 10 mg/kg b.w. tritium-labeled DVD using radioactive tracing coupled with liquid chromatography-electron spray ionization-ion trap-time-of-flight-mass spectrometry (LC-ESI-IT-TOF/MS). The metabolic pathways involved demethylation, α-hydroxylation, glucuronidation, and sulfonylation and produced four metabolites in swine (M0, DVD; M1, 3'/4'-demethyl-DVD; M2, 3'/4'-demethyl-DVD-O-glucuronide; M4, 2/4-glucuronidated-DVD) and five in chickens (M0∼M2; M3, α-hydroxy-DVD; M4) and rats (M0∼M3; M5, 3'/4'-demethyl-DVD-O-sulfation). M0 was dominant in the excreta of chicken and female and male rats, while M2 was mainly excreted in swine. Among the three species studied, M0 was the most persistent in the kidneys (t1/2 3.15-3.89 d); therefore, M0 kidney levels are residue monitoring targets. This study enabled a thorough comprehension of the metabolism and pharmacokinetic characteristics of DVD in animals.

Defibrotide improved the outcome of monocrotaline induced rat hepatic sinusoidal obstruction syndrome.

BACKGROUND AND AIM: Pyrrolizidine alkaloids (PA) induced hepatic sinusoidal obstruction syndrome (HSOS) occurred worldwide and the mortality rate remained high because there were no specific therapies. Defibrotide was effective for HSOS following hematopoietic stem cell transplantation. But the pathogenesis of the two types of HSOS were not equivalent. The purpose of this study was to see if defibrotide was also effective in PA induced rat HSOS. METHODS: First we improved rat HSOS model by using higher dose (230 mg/kg) of monocrotaline (a kind of PA) as the dose of median lethal dose. So drug effectiveness could be assessed by survival time. Next, male SD rats were divided into 5 groups. They were control group, model group, low dose low molecular weight heparin (LMWH) treatment group, high dose LMWH treatment group and defibrotide treatment group. Rats' survival time, liver function, white blood cell count and cytokines were compared among the groups. The DeLeve score was used to assess the severity of liver pathology. RESULTS: The model group exhibited typical liver pathology of HSOS, such as hepatic sinus dilation, congestion, endothelial injury of central lobular vein, coagulative necrosis of hepatocytes and fibrin deposition in the subendothelial. The pathologic characteristics indicated that the model was built up successfully. The survival rate was significantly higher in defibrotide group (81.8%) than model group (43.7%), while the survival rates were similar in the two LMWH groups (62.5% and 75%) and model group. The survival time only be prolonged by defibrotide (P=0.028) but not LMWH (P>0.05). DeLeve score was improved most in the defibrotide group than the two LMWH groups (both P<0.01). Changes in DeLeve score, liver function, plasma level of tumor necrosis factor α and plasminogen activator inhibitor-1 exhibited the same trends. CONCLUSION: Defibrotide could improve the outcome of monocrotaline-induced rat HSOS indicating that defibrotide might be a better choice than LMWH in clinical practice.

Decoupled Electrochemical Hydrazine "Splitting" via a Rechargeable Zn-Hydrazine Battery.

Hydrogen generation via electrochemical splitting plays an important role to achieve hydrogen economy. However, the large-scale application is highly limited by high cost and low efficiency. Herein, a new type of rechargeable Zn-hydrazine (Zn-Hz) battery is proposed and realized by a bifunctional electrocatalyst based on two separate cathodic reactions of hydrogen evolution (discharge: 2H2 O + 2e-  â†’ H2  + 2OH- ) and hydrazine oxidation (charge: 1 / 2 N 2 H 4 + 2 OH - → 1 / 2 N 2 + 2 H 2 O + 2 e - $1{\rm{/}}2\,{{\rm{N}}_2}{{\rm{H}}_4}{\bm{ + }}2{\rm{O}}{{\rm{H}}^{\bm{ - }}}{\bm{ \to }}1{\rm{/}}2\,{{\rm{N}}_2}{\bm{ + }}2{{\rm{H}}_2}{\rm{O}}{\bm{ + }}2{e^{\bm{ - }}}$ ). This Zn-Hz battery, driven by temporally decoupled electrochemical hydrazine splitting on the cathode during discharge and charge processes, can generate separated hydrogen without purification. When the highly active bifunctional cathode of 3D Mo2 C/Ni@C/CS is paired with Zn foil, the Zn-Hz battery can achieve efficient hydrogen generation with a low energy input of less than 0.4 V (77.2 kJ mol-1 ) and high energy efficiency of 96%. Remarkably, this battery exhibits outstanding long-term stability for 600 cycles (200 h), achieving continuous hydrogen production on demand, which presents great potential for practical application.

Dosing Regimen of Aditoprim and Sulfamethoxazole Combination for the Glaesserella parasuis Containing Resistance and Virulence Genes.

Glaesserella parasuis (G. parasuis) causes Glasser's disease in pigs and causes high mortality in piglets. The new drug Aditoprim (ADP) alone or combined with Sulfamethoxazole (SMZ) is one of the good choices for treating respiratory infections. The objective of this study was to recommend the optimal dosing regimen for the treatment of G. parasuis infection which contains resistance and virulence genes by ADP/SMZ compound through pharmacokinetics-pharmacodynamics (PK-PD) modeling. The whole genome of the virulent strain G. parasuis H78 was obtained and annotated by whole genome sequencing. The results show that G. parasuis H78 consists of a unilateral circular chromosome with prophages in the genome. The annotation results of G. parasuis H78 showed that the genome contained a large number of virulence-related genes and drug resistance-related genes. The in vitro PD study showed that the antibacterial effect of ADP/SMZ compound against G. parasuis was time-dependent, and AUC/MIC was selected as the PK-PD modeling parameter. The PK study showed that the content of ADP/SMZ compound in pulmonary epithelial lining fluid (PELF) was higher than plasma, and there were no significant differences in ADP and SMZ PK parameters between the healthy and infected group. The dose equation to calculate the optimal dosing regimen of ADP/SMZ compound administration for control of G. parasuis infection was 5/25 mg/kg b.w., intramuscular injection once a day for 3~5 consecutive days. The results of this study provide novel therapeutic options for the treatment of G. parasuis infection to decrease the prevalence and disease burden caused by G. parasuis.

rocF affects the production of tetramethylpyrazine in fermented soybeans with Bacillus subtilis BJ3-2.

BACKGROUND: Tetramethylpyrazine (TTMP) is a flavoring additive that significantly contributes to the formation of flavor compounds in soybean-based fermented foods. Over recent years, the application of TTMP in the food industry and medicine has been widely investigated. In addition, several methods for the industrial-scale production of TTMP, including chemical and biological synthesis, have been proposed. However, there have been few reports on the synthesis of TTMP through amino acid metabolic flux. In this study, we investigated genetic alterations of arginine metabolic flux in solid-state fermentation (SSF) of soybeans with Bacillus subtilis (B.subtilis) BJ3-2 to enhance the TTMP yield. RESULTS: SSF of soybeans with BJ3-2 exhibited a strong Chi-flavour (a special flavour of ammonia-containing smelly distinct from natto) at 37 °C and a prominent soy sauce-like aroma at 45 °C. Transcriptome sequencing and RT-qPCR verification showed that the rocF gene was highly expressed at 45 °C but not at 37 °C. Moreover, the fermented soybeans with BJ3-2ΔrocF (a rocF knockout strain in B. subtilis BJ3-2 were obtained by homologous recombination) at 45 °C for 72 h displayed a lighter color and a slightly decreased pH, while exhibiting a higher arginine content (increased by 14%) than that of BJ3-2. However, the ammonia content of fermented soybeans with BJ3-2ΔrocF was 43% lower than that of BJ3-2. Inversely, the NH4+ content in fermented soybeans with BJ3-2ΔrocF was increased by 28% (0.410 mg/kg). Notably, the TTMP content in fermented soybeans with BJ3-2ΔrocF and BJ3-2ΔrocF + Arg (treated with 0.05% arginine) were significantly increased by 8.6% (0.4617 mg/g) and 18.58% (0.504 mg/g) respectively than that of the BJ3-2. CONCLUSION: The present study provides valuable information for understanding the underlying mechanism during the TTMP formation process through arginine metabolic flux.

The Application of Hollow Fiber Cartridge in Biomedicine.

The hollow fiber cartridge has the advantages of good semi-permeability, high surface area to volume ratio, convenient operation, and so on. Its application in chemical analysis, drug in vitro experiment, hemodialysis, and other fields has been deeply studied. This paper introduces the basic structure of hollow fiber cartridge, compares the advantages and disadvantages of a hollow fiber infection model constructed by a hollow fiber cartridge with traditional static model and animal infection model and introduces its application in drug effects, mechanism of drug resistance, and evaluation of combined drug regimen. The principle and application of hollow fiber bioreactors for cell culture and hollow fiber dialyzer for dialysis and filtration were discussed. The hollow fiber cartridge, whether used in drug experiments, artificial liver, artificial kidney, etc., has achieved controllable experimental operation and efficient and accurate experimental results, and will provide more convenience and support for drug development and clinical research in the future.

A new drug-drug interaction-tilmicosin reduces the metabolism of enrofloxacin through CYP3A4.

The monitoring results in China have shown that the phenomenon of single-pollutant residues exceeding the standard in food has decreased, while the coexistence of many low-level residual pollutants has increased significantly. Among these, the combined use of enrofloxacin (EF) and tilmicosin (TIM) is serious. Despite that, little is comprehended about influences of the drug-drug interactions (DDIs) caused by EF and TIM. The purpose of this work is to evaluate the effects caused by the combination of these two drugs on metabolism and residues in vivo and in vitro. The results showed that TIM affected the metabolism of EF by inhibiting CYP3A4 and increased the residual concentrations of EF in broilers. Moreover, the time of elimination of EF was prolonged. Thus, the combined use of TIM and EF must be reduced in veterinary drugs and feeds in order to ensure the safety of humans and animals.

Migration and toxicity of toltrazuril and its main metabolites in the environment.

Veterinary drugs heavily used in livestock are passed into the environment through different ways, resulting in risks to terrestrial environments and humans. The migration of toltrazuril (TOL), an important anticoccidial drug used intensively in livestock, and its main metabolites between the chicken manure compost, soil and vegetables was investigated, and then the impacts of TOL on the soil bacterial community and ARGs, soil enzyme activities and phytotoxicity were detected. In the process of aerobic composting for 80 days, except for toltrazuril sulfoxide (the degradation half-life was 59.74 d), TOL and ponazuril (PON) were not significantly degraded. However, TOL and its metabolites were significantly degraded in fertilized soil, and the degradation half-life was 28.17-346.50 d. Among the three drugs, only PON could migrate from soil to vegetables, and the residual concentrations of PON in lettuce and radish were 2.64-70.02 µg kg-1 and 0-2.80 µg kg-1, respectively. Moreover, TOL and its main metabolisms had no significant effect on the bacterial community structure and the abundance of antibiotic resistance genes during composting, but affected the microbial activity in the soil. The presence of TOL and its main metabolites reduced soil urease activity, increased catalase activity, and decreased alkaline phosphatase activity at the beginning and then increased slightly. They had negative effects on plant growth. Compared with the control group, the inhibition rates of TOL and its metabolites on lettuce and radish seed germination were 8.33% and 26.74% respectively, and the inhibition rates of root elongation length were 25.88% and 34.45% respectively. These results showed that TOL and its main metabolites were ineffectively removed by aerobic composting, and could be migrated from composting to soil and vegetables, which had adverse effects on soil enzyme activity and plant growth. Therefore, its environmental ecological risk and human health risk needs to be further evaluated.

Effects of composting on the fate of doxycycline, microbial community, and antibiotic resistance genes in swine manure and broiler manure.

Aerobic composting is an economical and effective technology that is widely used to treat animal manure. To study the fate of doxycycline (DOX), the microbial community, and antibiotic resistance genes (ARGs) during composting, aerobic composting of broiler manure and swine manure was carried out under natural environmental conditions. Aerobic composting effectively removed DOX (with a removal rate > 97%) and most ARGs from animal manure. The microbial diversity and the numbers of ARGs were higher in composted swine manure compared with composted broiler manure. The microbial community structure changed during composting, and the dominant phyla of broiler manure and swine manure changed from Firmicutes to Bacteroidetes and Proteobacteria, respectively. DOX changed the structure and relative abundance of the microbial community during composting, and the relative abundance of multidrug resistance genes and mobile genetic elements (MGEs) increased, which might lead to the risk of transmission of resistance in the environment. The C / N ratio, DOX concentration, Firmicutes, intl1, and intl2 were the key factors driving the change in ARGs during composting. These results help to reveal the effects of DOX on microbial communities, ARGs, and MGEs during composting and clarify the possible ways to reduce the risk of resistance gene transmission in the environment.

Optimization and Validation of Dosage Regimen for Ceftiofur against Pasteurella multocida in Swine by Physiological Based Pharmacokinetic-Pharmacodynamic Model.

Model informed drug development is a valuable tool for drug development and clinical application due to its ability to integrate variability and uncertainty of data. This study aimed to determine an optimal dosage of ceftiofur against P. multocida by ex vivo pharmacokinetic/pharmacodynamic (PK/PD) model and validate the dosage regimens by Physiological based Pharmacokinetic-Pharmacodynamic (PBPK/PD) model. The pharmacokinetic profiles of ceftiofur both in plasma and bronchoalveolar lavage fluid (BALF) are determined. PD performance of ceftiofur against P. multocida was investigated. By establishing PK/PD model, PK/PD parameters and doses were determined. PBPK model and PBPK/PD model were developed to validate the dosage efficacy. The PK/PD parameters, AUC0-24 h/MIC, for bacteriostatic action, bactericidal action and elimination were determined as 44.02, 89.40, and 119.90 h and the corresponding dosages were determined as 0.22, 0.46, and 0.64 mg/kg, respectively. AUC24 h/MIC and AUC 72 h/MIC are simulated by PBPK model, compared with the PK/PD parameters, the therapeutic effect can reach probability of target attainment (PTA) of 90%. The time-courses of bacterial growth were predicted by the PBPK/PD model, which indicated the dosage of 0.46 mg/kg body weight could inhibit the bacterial growth and perform good bactericidal effect.

Optimal Regimens and Clinical Breakpoint of Avilamycin Against Clostridium perfringens in Swine Based on PK-PD Study.

Clostridium perfringens causes significant morbidity and mortality in swine worldwide. Avilamycin showed no cross resistance and good activity for treatment of C. perfringens. The aim of this study was to formulate optimal regimens of avilamycin treatment for C. perfringens infection based on the clinical breakpoint (CBP). The wild-type cutoff value (COWT) was defined as 0.25 µg/ml, which was developed based on the minimum inhibitory concentration (MIC) distributions of 120 C. perfringens isolates and calculated using ECOFFinder. Pharmacokinetics-pharmacodynamics (PK-PD) of avilamycin in ileal content were analyzed based on the high-performance liquid chromatography method and WinNonlin software to set up the target of PK/PD index (AUC0-24h/MIC)ex based on sigmoid Emax modeling. The PK parameters of AUC0-24h, Cmax, and Tmax in the intestinal tract were 428.62 ± 14.23 h µg/mL, 146.30 ± 13.41 µg/ml,, and 4 h, respectively. The target of (AUC0-24h/MIC)ex for bactericidal activity in intestinal content was 36.15 h. The PK-PD cutoff value (COPD) was defined as 8 µg/ml and calculated by Monte Carlo simulation. The dose regimen designed from the PK-PD study was 5.2 mg/kg mixed feeding and administrated for the treatment of C. perfringens infection. Five respective strains with different MICs were selected as the infection pathogens, and the clinical cutoff value was defined as 0.125 µg/ml based on the relationship between MIC and the possibility of cure (POC) following nonlinear regression analysis, CART, and "Window" approach. The CBP was set to be 0.25 µg/ml and selected by the integrated decision tree recommended by the Clinical Laboratory of Standard Institute. The formulation of the optimal regimens and CBP is good for clinical treatment and to control drug resistance.

Rational Use of Danofloxacin for Treatment of Mycoplasma gallisepticum in Chickens Based on the Clinical Breakpoint and Lung Microbiota Shift.

The study was to explore the rational use of danofloxacin against Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and the effect on lung microbiota. The CBP was established according to epidemiological cutoff value (ECV/COWT), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (COPD) and clinical cutoff value (COCL). The ECV was determined by the micro-broth dilution method and analyzed by ECOFFinder software. The COPD was determined according to PK-PD modeling of danofloxacin in infected lung tissue with Monte Carlo analysis. The COCL was performed based on the relationship between the minimum inhibitory concentration (MIC) and the possibility of cure (POC) from clinical trials. The CBP in infected lung tissue was 1 µg/mL according to CLSI M37-A3 decision tree. The 16S ribosomal RNA (rRNA) sequencing results showed that the lung microbiota, especially the phyla Firmicutes and Proteobacteria had changed significantly along with the process of cure regimen (the 24 h dosing interval of 16.60 mg/kg b.w for three consecutive days). Our study suggested that the rational use of danofloxacin for the treatment of MG infections should consider the MIC and effect of antibiotics on the respiratory microbiota.

Ceruloplasmin inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma cells and is negatively regulated by miR-543.

BACKGROUND: Ceruloplasmin (CP), recognized as a member of multicopper oxidase family, is related to the progression of diverse cancers in human beings. This study is designed to clarify the expression characteristics, biological function and related mechanism of CP in nasopharyngeal carcinoma (NPC). METHODS: CP expression in NPC tissues and cells was probed by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and Western blot. After gain-of-function and loss-of-function models were established, cell counting kit-8 (CCK-8), Transwell and BrdU assays were employed to measure cell viability, migration and invasion. The targeting relationship between microRNA-543 (miR-543) and CP was verified by dual-luciferase reporter gene assay. RESULTS: As against normal nasopharyngeal epithelial tissues, CP expression was significantly lower in NPC tissues, which was associated with higher clinical stage and the short overall survival time. Compared with the control group, CP overexpression markedly restrained the growth, migration and invasion of NPC cells; knocking down CP had the opposite effect. MiR-543 directly targeted CP and negatively modulated its expression. CONCLUSION: CP restrains the growth, migration and invasion of NPC cells and is negatively regulated by miR-543.