Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke.

BACKGROUND: Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance. METHODS AND RESULTS: This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores. CONCLUSIONS: An increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Differential bone remodeling mechanism in hindlimb unloaded and hibernating Daurian ground squirrels: a comparison between artificial and natural disuse within the same species.

Loss of bone mass can occur in mammals after prolonged disuse but the situation for hibernators that are in a state of torpor for many months of the year is not yet fully understood. The present study assesses the bone remodeling mechanisms present in Daurian ground squirrels (Spermophilus dauricus) during hibernation as compared with a model of hindlimb disuse. Differences in microstructure, mechanical properties, bone remodeling-related proteins (Runx2, OCN, ALP, RANKL, CTK and MMP-9) and key proteins of Wnt/ß-catenin signaling pathway (GSK-3ß and phospho-ß-catenin) were evaluated in ground squirrels under 3 conditions: summer active (SA) vs. hibernation (HIB) vs. hindlimb unloaded (HLU). The results indicated that the body weight in HLU ground squirrels was lower than the SA group, and the middle tibia diameter in the HLU group was lower than that in SA and HIB groups. The thickness of cortical and trabecular bone in femurs from HLU ground squirrels was lower than in SA and HIB groups. Most parameters of the tibia in the HLU group were lower than those in SA and HIB groups, which indicated cortical bone loss in ground squirrels. Moreover, our data showed that the changes in microscopic parameters in the femur were more obvious than those in the tibia in HLU and HIB ground squirrels. The levels of Runx2 and ALP were lower in HLU ground squirrels than SA and HIB groups. The protein levels of OCN were unchanged in the three groups, but the protein levels of ALP were lower in the HLU group than in SA and HIB groups. RANKL, CTK and MMP-9 protein levels were significantly decreased in tibia of HLU ground squirrels as compared with SA and HIB groups. In addition, the protein expression levels of RANKL, CTK and MMP-9 showed no statistical difference between SA and HIB ground squirrels. Thus, the mechanisms involved in the balance between bone formation and resorption in hibernating and hindlimb unloading ground squirrels may be different. The present study showed that in femur, the Wnt signaling pathway was inhibited, the protein level of GSK-3ß was increased, and the protein expression of phospho-ß-catenin was decreased in the HIB group as compared with the SA group, which indicates that the Wnt signaling pathway has a great influence on the femur of the HIB group. In conclusion, the natural anti-osteoporosis properties of Daurian ground squirrels are seasonal. The squirrels do not experience bone loss when they are inactive for a long time during hibernation, but the mechanisms of anti-osteoporosis did not work in HLU summer active squirrels.

Development of red apple pomace extract/chitosan-based films reinforced by TiO2 nanoparticles as a multifunctional packaging material.

A chitosan-based (CS) film was developed with nanosized TiO2 and red apple pomace extract (APE). The intermolecular interactions of CS, TiO2 and APE were evaluated by Fourier transform infrared spectroscopy, scanning electron microscopy and X-ray diffraction. TiO2 nanoparticles remarkably improved the water vapor and UV-Vis light barrier properties, mechanical strength and thermal stability of CS-APE films. The strong antioxidant abilities of CS-APE and CS-TiO2-APE films were characterized. Nano-TiO2 and APE showed a synergistic enhancement of the antimicrobial activity in CS matrix. The addition of TiO2 nano-particles into CS-APE films resulted the sensitive color variations, which applied successfully as an indicator to monitor the freshness of salmon fillets. Consequently, the development of CS-APE-TiO2 film provides a new solution to convert rad apple pomace to an active and multifunctional food packaging material with considerable mechanical, antibacterial, antioxidant and pH-responsive color-changing properties.

The inhibitory effects and mechanisms of polymannuroguluronate sulfate against human papillomavirus infection in vitro and in vivo.

Human papillomaviruses (HPVs) are non-enveloped DNA viruses that infect epithelia and can cause a wide variety of benign and pre-malignant epithelial tumours. The sulfated polysaccharides such as carrageenans were reported to be able to interfere with the binding process of HPV to the cell surface. In this study, brown seaweed derived polysaccharides polymannuroguluronate sulfate (PMGS) were prepared, and their anti-HPV effects were explored in vitro and in vivo. The results indicated that PMGS effectively inhibited high-risk HPV16 and HPV45 infection with very low toxicity. PMGS may inactivate HPV particles or block the binding and entry process of HPV through direct interaction with viral capsid proteins. PMGS can enter into HeLa cells and down-regulate the expression levels of viral oncogene proteins E6 and E7. In addition, PMGS also dramatically inhibited HPV infection on the skin of BALB/c Nude Mice. Thus, marine derived polysaccharide PMGS possessed anti-HPV activities in vitro and in vivo, and may block HPV infection via targeting viral capsid L1 protein, suggesting that it has great potential to be developed into a novel anti-HPV agent in the future.

Inhibition of herpes simplex virus by myricetin through targeting viral gD protein and cellular EGFR/PI3K/Akt pathway.

Myricetin, a common dietary flavonoid, was reported to possess many different biological activities such as anti-oxidant, anti-inflammatory, and antiviral effects. In this study, we explored the anti-HSV effects and mechanisms of myricetin both in vitro and in vivo. The results showed that myricetin possessed anti-HSV-1 and HSV-2 activities with very low toxicity, superior to the effects of acyclovir. Myricetin may block HSV infection through direct interaction with virus gD protein to interfere with virus adsorption and membrane fusion, which was different from the nucleoside analogues such as acyclovir. Myricetin also down-regulate the cellular EGFR/PI3K/Akt signaling pathway to further inhibit HSV infection and its subsequent replication. Most importantly, intraperitoneal therapy of myricetin markedly improved mice survival and reduced virus titers in both lungs and spinal cord. Therefore, the natural dietary flavonoid myricetin has potential to be developed into a novel anti-HSV agent targeting both virus gD protein and cellular EGFR/PI3K/Akt pathway.

The suppression effects of feeding and mechanisms in CRF system of animals.

CRF system is comprised of 4 homologous lineages, 2 main receptors (CRF-R1 and CRF-R2), and a binding protein CRF-BP. The homologous lineages are corticotropin-releasing factor (CRF), urotensin I (UI)/sauvagine (SVG)/urocortin 1 (UCN1), urocortin 2 (UCN2), and urocortin 3 (UCN3), and UI, SVG, UCN1 are orthologous genes. CRF system genes are widely distributed in the brain and gastrointestinal tract, which may relate to feeding regulation. According the research progress about CRF system on mammals and non-mammals, this paper summarized the discovery, structure, tissue distribution, appetite regulation and mechanism of CRF system in animals, which can provide the reference for further research and production of feeding regulation and growth in mammals and fish species.

Increased expression of Triad1 is associated with neuronal apoptosis after intracerebral hemorrhage in adult rats.

Objective: It has been demonstrated that Triad1 (2 RING fingers and double RING finger linked 1) negatively regulates myeloid cell growth and induces cell apoptosis. However, its functions in intracerebral hemorrhage (ICH) disease have not been conducted. In this study, the role of Triad1 in rat model of ICH was explored.Methods: We observe an increasing expression of Triad1 in areas adjacent to hematoma after ICH. Immunofluorescence shows that Triad1 is colocalized with neurons, while not microglia or astrocyte, indicates its correlation with neuronal activities following ICH.Results: As neuronal apoptosis is the most crucial event in ICH disease, the expression of active caspase-3 and p53 is also enhanced around the hematoma, which is consistent with Triad1 in expression tendency. In turn, Triad1 depletion in primary cortical neurons decreased the apoptosis of neurons after using Triad1 shRNA.Conclusion: We conclude that inhibition of Triad1 expression might protect the brain from secondary damage following ICH.

Positive Effect of Magnetic-Conductive Bifunctional Fibrous Scaffolds on Guiding Double Electrical and Magnetic Stimulations to Pre-Osteoblasts.

Development of bone tissue engineering has provided a promising method for bone rehabilitation. Tissue engineering scaffolds with magnetic or conductive properties may conduct electric or magnetic signals and bring out synergetic promoting effect to cells growth. In this work, polypyrrole (PPy)/Fe3O4/polylactic acid-glycolic acid (PLGA) magnetic-conductive bifunctional fibrous scaffolds were prepared through in-situ polymerization of pyrrole on Fe3O4/PLGA fibers. The prepared magnetic-conductive bifunctional PPy/Fe3O4/PLGA fibrous scaffolds showed good conductive and magnetic properties to deliver electrical and magnetic signals. The PPy/Fe3O4/PLGA fibrous scaffolds had a conductivity of 0.58 S/cm at 180 mM pyrrole and still remained with good fibrous morphology. MC3T3-E1 pre-osteoblasts inoculated on PPy/Fe3O4/ PLGA scaffolds under double electrical stimulation (ES) and magnetic stimulation (MS) demonstrated highest cell viabilities compared with those under single ES, MS or without any stimulation. The enhancement of cell viabilities by the Fe3O4/PLGA and PPy/Fe3O4/PLGA fibrous scaffolds from 1 to 5 d culture indicate that both of them had good biocompatibility. MS can also induce cell alignment arrangement on the magnetic scaffolds according to resultant cell scanning electron microscope (SEM) images. In addition, better hydrophilicity and thermal stability of the PPy/Fe3O4/PLGA fibrous scaffolds, as compared to Fe3O4/PLGA fibrous scaffolds, allowed the bifunctional scaffolds wide application in bone tissue engineering.

Development of ultrasound treated polyvinyl alcohol/tea polyphenol composite films and their physicochemical properties.

In this study, polyvinyl alcohol (PVA) was used as a film-forming substrate, added to extracted tea polyphenols (TPs) in various ratios and processed with ultrasonication to form films using the tape-casting method. The effects of ultrasonic processing duration on the properties of PVA/TP antibacterial active materials were explored via material property testing. The results showed that, overall, ultrasonic processing degraded the tensile strength and elongation at break of the composite films. When PVA/TP composite films with a PVA-to-TP mass ratio of 8:2 were processed with ultrasonication for 30 min, the swelling capacity was (740.19 ±â€¯64.67)% and solubility was (5.26 ±â€¯1.31)%. Ultrasonication also improved the degradability and barrier properties of composite films. Moreover, 8/2 composite films with the PVA/TP ratio of 8:2 exhibited excellent bacteriostatic properties; after ultrasonication processing, the films had a bacteriostatic rate of (95.5 ±â€¯4.2)% and (91.8 ±â€¯3.7)% against Staphylococcus aureus and Escherichia coli, respectively, making them suitable for use as antibacterial active materials in food packaging.

Cab45s inhibits neuronal apoptosis following intracerebral hemorrhage in adult rats.

Recent studies have shown that Cab45s, belonging to the CREC family, can fight against apoptosis in the cancer cell lines. Here, we report that Cab45s may involve in neuronal apoptosis at the early stage of intracerebral hemorrhage (ICH) in pathophysiology. We found that expression of Cab45s was enhanced in areas contiguous to hematoma following ICH in adult rats, and that so were the expressions of Glucose-regulated protein 78 (GRP78), pro-apoptotic Bcl-2-associated X protein (Bax) and active caspase-3. In vitro, coimmunoprecipitation analysis indicated the interaction between Cab45s and GRP78. Depletion of Cab45s attenuated the expression of GRP78, but increased the expressions of Bax and caspase-3 in PC12 cells treated with hemin, which finally promoted apoptosis. Together, these results reveal that Cab45s might exert its anti-apoptotic function against neuronal apoptosis. Thus, the study may provide evidences for regulating Cab45s as a potentially reliable treatment for the secondary damage following ICH.

Preparation and properties of polylactic acid-tea polyphenol-chitosan composite membranes.

To study the properties of composite membranes consisting of polylactic acid (PLA), tea polyphenol (TP), and chitosan (CS), the stretch film method was employed to make PLA-TP- CS composite membranes of different concentrations. By testing the density, mechanical properties, heat-sealing performance, water vapor permeability, and solubility of the pure PLA membrane and the composite membranes, the comprehensive performance of the composite membranes were analyzed with regard to the actual use value. The results show that, compared with the pure PLA membrane, adding TP and CS significantly increases the heat-sealing strength, water vapor permeability, and solubility of the composite membrane. When the composite membrane is used for the preservation of cherries, it is found that the composite membrane with the mass ratio of TP to CS of 3:7 can decrease the rotting rate and mass loss rate significantly, postpone the consumption of soluble solids and vitamin C, maintain the quality of the cherries, and extend the shelf life, thus proving its potential for application in food packaging.

Up-Regulation of Cdc37 Contributes to Schwann Cell Proliferation and Migration After Sciatic Nerve Crush.

Cell division cycle protein 37 (Cdc37), a molecular chaperone takes part in a series of cellular processes including cell signal transduction, cell cycle progression, cell proliferation, cell motility, oncogenesis and malignant progression. It can not only recruit immature protein kinases to HSP90 but also work alone. Cdc37 was reported to be associated with neurogenesis, neurite outgrowth, axon guidance and myelination. However, the roles of Cdc37 on Schwann cells (SC) after peripheral nerve injury (PNI) remain unknown. In this study, we found that the expression of Cdc37 increased and reached the peak at 1 week after sciatic nerve crush (SNC), which was consistent with that of proliferation cell nuclear antigen. Immunofluorescence verified that Cdc37 co-localized with SC in vivo and in vitro. Intriguingly, Cdc37 protein level was potentiated in the model of TNF-α-induced SC proliferation. Moreover, we found that Cdc37 silencing impaired proliferation of SC in vitro. Moreover, Cdc37 suppression attenuated kinase signaling pathways of Raf-ERK and PI3K/AKT which are crucial cell signaling for SC proliferation. Finally, we found that Cdc37 silencing inhibited SC migration in vitro. In conclusion, we demonstrated that the way Cdc37 contributed to SC proliferation is likely via activating kinase signaling pathways of Raf-ERK and PI3K/AKT, and CDC37 was also involved in SC migration after SNC.

SSTR2 associated with neuronal apoptosis after intracerebral hemorrhage in adult rats.

Objective SSTR2 is a member of superfamily of SST receptor (SSTR), and widely expressed in the brain; however, the knowledge of its functions in area adjacent to hematoma after intracerebral hemorrhage (ICH) is still limited. Method The role of SSTR2 in the processes of ICH was explored by conducting an ICH rat model. Western blot and immunohistochemistry were employed to examine the level of SSTR2 in area adjacent to hematoma after ICH. Immunofluorescent staining was used to observe the spatial correlation of SSTR2 with cellular types adjacent to hematoma after ICH. RNA interference specific to SSTR2 was adopted in PC12 cells to clarify the causal correlation between SSTR2 and neuronal activities. Results Increased expression of SSTR2 was observed and restricted to the neurons adjacent to hematoma following ICH. Immunofluorescent staining showed that SSTR2 was significant increased in neurons, but not astrocytes or microglia. Increasing SSTR2 level was found to be accompanied by the up-regulation of activated caspase-3 and the down-expression of p-Akt in a time-dependent manner. What's more, using SSTR2 RNA interference (SSTR2-RNAi) in PC12 cells, we indicated that SSTR2 might have a pro-apoptotic role in neurons. Conclusion We speculated that SSTR2 might exert its pro-apoptotic function in neurons through inhibiting Akt activity following ICH.

Electrospun Antimicrobial Polylactic Acid/Tea Polyphenol Nanofibers for Food-Packaging Applications.

The development of new bioactive food-packaging materials that extend the shelf life of food is an important objective. Herein, we report the fabrication of four polylactic acid/tea polyphenol (PLA/TP) composite nanofibers, with PLA/TP ratios of 5:1, 4:1, 3:1, and 2:1, by electrospinning. The morphological quality of each sample was examined by scanning electron microscopy (SEM), and samples with higher TP content were found to be deeper in color. The samples were then examined by Fourier transform infrared (FTIR) spectroscopy to confirm the presence of TP. Examination of the mechanical properties of these fibers revealed that the presence of TP decreased both tensile strength and elongation at break; however, this decrease was only slight for the PLA/TP-3:1 composite fiber. The addition of TP influenced the hydrophilic⁻hydrophobic property and release behavior of the composite fibers, which significantly improved the antioxidant behavior of these samples, with 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging capacities of up to 95.07% ± 10.55% observed. Finally, antimicrobial activities against Escherichia coli and Staphylococcus aureus of up to 92.26% ± 5.93% and 94.58% ± 6.53%, respectively, were observed for the PLA/TP-3:1 composite fiber. The present study demonstrated that PLA/TP composite nanofibers can potentially be used for food-packaging applications that extend food shelf life.

Simultaneous determination of isochamaejasmin, neochamaejasmin A and aphnoretinin rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study of Stellera chamaejasme L. extract.

Isochamaejasmin, neochamaejasmin A and daphnoretin derived from Stellera chamaejasme L. are important because of their reported anticancer properties. In this study, a sensitive UPLC-MS/MS method for the determination of isochamaejasmin, neochamaejasmin A and daphnoretin in rat plasma was developed. The analyte and IS were separated on an Acquity UPLC HSS T3 column (100 × 2.1 mm, 1.8 µm) using gradient elution with the mobile phase of aqueous solution (methanol-water, 1:99, v/v, containing 1 mm formic acid) and organic solution (methanol-water, 99:1, v/v, containing 1 mm formic acid) at a flow rate of 0.3 mL/min. Multiple reaction monitoring mode with negative electrospray ionization interface was carried out to detect the components. The method was validated in terms of specificity, linearity, accuracy, precision, stability, etc. Excellent linear behavior was observed over the certain concentration ranges with the correlation coefficient values >0.99. Intra- and inter-day precisions (RSD) were <6.7% and accuracy (RE) ranged from -7.0 to 12.0%. The validated method was successfully applied to investigate the pharmacokinetics of three chemical ingredients after oral administration of S. chamaejasme L. extract to rats.

Effect of Dietary Acidolysis-Oxidized Konjac Glucomannan Supplementation on Serum Immune Parameters and Intestinal Immune-Related Gene Expression of Schizothorax prenanti.

The present study was conducted to investigate the effects of dietary acidolysis-oxidized konjac glucomannan (A-OKGM) (0%, 0.4%, 0.8%, and 1.6%) supplementation on the immunity and expression of immune-related genes in Schizothorax prenanti. After feeding for eight weeks, the serum and guts were used for measurement of biochemical parameters, and immune-related gene expression in the gut were also analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). C-reactive protein and IgM levels were significantly higher in the A-OKGM fed groups than in the control group, regardless of the dosage. The 0.4% and 1.6% A-OKGM groups showed significant up-regulation of tumor necrosis factor α (TNFα) in the anterior gut. The 0.8% and 1.6% A-OKGM groups also showed significantly enhanced TNFα expression in the mid- and distal guts. Interleukin-1ß (IL-1ß) expression in the anterior gut of fish fed with 0.4% and 1.6% A-OKGM diets was significantly enhanced. The 0.8% and 1.6% A-OKGM diets resulted in significantly increased the expression of IL-1ß in the distal gut. Similarly, the interleukin-6 (IL-6) messenger RNA (mRNA) levels in the 0.4% and 1.6% diet groups were significantly higher in the anterior gut. The 0.8% and 1.6% A-OKGM diet groups showed significant induction of IL-6 gene expression in the distal gut. A-OKGM modified from KGM can act as an immunostimulant to enhance the immunity of S. prenanti.

A rhamnan-type sulfated polysaccharide with novel structure from Monostroma angicava Kjellm (Chlorophyta) and its bioactivity.

A homogeneous polysaccharide was obtained from Monostroma angicava Kjellm by water extraction, preparative anion-exchange and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that the polysaccharide was a glucuronic acid-containing rhamnan-type sulfated polysaccharide. The backbone mainly consisted of →3)-α-l-Rhap-(1→ and →2)-α-l-Rhap-(1→ residues, partially sulfated at C-2 of →3)-α-l-Rhap-(1→ and C-3/C-4 of →2)-α-l-Rhap-(1→. The branching contained unsulfated or monosulfated 3-linked, 2-linked, 4-linked α-l-rhamnose and terminal ß-d-glucuronic acid residues. The polysaccharide had strong antidiabetic activity assessed by glucose consumption, total cholesterol and triglyceride levels using human hepatocellular carcinoma (HepG2) and insulin-resistant HepG2 cells. The polysaccharide exhibited high anticoagulant property by activated partial thromboplastin time and thrombin time assays, and possessed high fibrin(ogen)olytic activity evaluated by plasminogen activator inhibitior-1, fibrin(ogen) degradation products and D-dimer levels using rats plasma. The investigation demonstrated that the polysaccharide from Monostroma angicava Kjellm was a novel sulfated rhamnan and could be a potential antidiabetic and anticoagulant polysaccharide.

Development of Poly(lactic acid)/Chitosan Fibers Loaded with Essential Oil for Antimicrobial Applications.

Cinnamon essential oil (CEO) was successfully encapsulated into chitosan (CS) nanoparticles at different loading amounts (1%, 1.5%, 2%, and 2.5% v/v) using oil-in-water (o/w) emulsion and ionic-gelation methods. In order to form active packaging, poly(lactic acid) (PLA) was used to fabricate PLA/CS-CEO composite fibers using a simple electrospinning method. The shape, size, zeta potential, and encapsulation efficacy of the CS-CEO nanoparticles were investigated. The composition, morphology, and release behavior of the composite fibers were investigated. PLA/CS-CEO-1.5 showed good stability and favorable sustained release of CEO, resulting in improved antimicrobial activity compared to the other blends. The PLA/CS-CEO fibers showed high long-term inactivation rates against Escherichia coli and Staphylococcus aureus due to the sustained release of CEO, indicating that the developed PLA/CS-CEO fibers have great potential for active food packaging applications.

Inhibition effects of novel polyketide compound PPQ-B against influenza A virus replication by interfering with the cellular EGFR pathway.

Development of anti-influenza A virus (IAV) drugs with novel targets and low toxicity is critical for preparedness against influenza outbreaks. In the current study, our results indicated that the novel polyketide compound purpurquinone B (PPQ-B) derived from acid-tolerant fungus Penicillium purpurogenum strain JS03-21 suppressed the replication of IAV in vitro with low toxicity, and may block some stages after virus adsorption. PPQ-B could inhibit H1N1 (A/Puerto Rico/8/34; PR8), H1N1 (A/California/04/2009; Cal09) and H3N2 (A/swine/Minnesota/02719/2009) virus replication in vitro, suggesting that PPQ-B possesses broad-spectrum anti-IAV activities. PPQ-B's antiviral activity may be largely related to its inhibition of some steps that occur 0-4 h after adsorption. Oral administration of PPQ-B could decrease pulmonary viral titers and improve survival rate in IAV infected mice. PPQ-B also significantly decreased the production of inflammatory factors TNF-α, IL-6, RANTES and KC in IAV infected lungs and A549 cells, suggesting that PPQ-B may also attenuate the inflammatory responses caused by IAV infection. PPQ-B may down-regulate the NF-κB and MAPK pathways to inhibit both virus replication and inflammatory responses. In summary, PPQ-B has the potential to be developed into a novel anti-IAV drug targeting host EGFR pathway in the future.

Liquid Chromatography-Mass Spectrometry/Mass Spectrometry Analysis and Pharmacokinetic Assessment of Ponatinib in Sprague-Dawley Rats.

INTRODUCTION: By means of liquid-liquid extraction with ethyl acetate, a rapid, sensitive, and specific LC-MS/MS method was developed and validated for assaying ponatinib and the internal standard, warfarin. METHODS: The method was verified and successfully applied to evaluate the pharmacokinetics of ponatinib in Sprague-Dawley rats. RESULTS: Ponatinib showed dose-dependent exposure in the circulation system, and the absolute bioavailabilities of ponatinib were 43.95 ± 2.40%, 47.69 ± 5.08% and 55.02 ± 2.50% after intragastric administration of 7.5, 15.0 and 30.0 mg/kg ponatinib in rats, respectively. After consecutive administration at 3.75 mg/kg for 7 days, there was distinct accumulation of ponatinib (AUC0-∞ = 5479.41 ± 757.07 µg h/L) relative to that of a single dose (AUC0-∞ = 2301.84 ± 787.10 µg h/L, p < 0.05), and the MRT increased from 16.77 ± 1.91 to 21.34 ± 1.27 h (p < 0.05). Analysis of ponatinib in various tissues revealed it was distributed widely in the body, highly exposed in the lung, thyroid, and lowly exposed in plasma, the brain, bone and the liver, indicating its potential action on lung cancer with lower system toxicity. Ponatinib was eliminated primarily in feces at 26.17 ± 7.70% of its original form and only 0.24 ± 0.10% in urine. CONCLUSION: For the first time, the pharmacokinetics of ponatinib were systematically evaluated in rats, which facilitated the study and development of the analogous candidates of ponatinib.