In situ hydrodeoxygenation of heavy bio-oil using a Ce/Fe-based oxygen carrier in methanol-zero valent aluminum media.

Resource recovery from solid organic wastes, such as degradable plastics, and upgrading raw bio-oil are important ways for reducing carbon and pollution emissions. Hydrodeoxygenation (HDO) is a common thermochemical treatment to upgrade crude bio-oil. In this study, in order to realize in situ HDO during the hydropyrolysis of heavy bio-oil and degradable plastics, a reduced Fe/Ce oxygen carrier (OC) was used to catalytically remove oxygen from organics under the methanol-zero valent aluminum (ZV Al) media, where the hydrogen was produced during pyrolysis instead of a direct hydrogen supply. The results showed that the reduced OC captured the oxygen from the pyrolysis products of heavy bio-oil and degradable plastic, representing the multi-selectivity of reduced OC to phenols, ketones, etc. The ZV Al system promoted the production and utilization of hydrogen, as evidenced by the increased hydrogen content in gas phase and hydrocarbon content in liquid phase. The hydrocarbon component distribution in the liquid phase increased clearly when hydropyrolysis with degradable plastics addtion, but the excess degradable plastics addition caused increasing of the liquid product viscosity, and decreasing of the liquid products yield for the higher ash content in degradable plastic, and a higher ZV Al amount was required to maintain the hydropyrolysis. Molecular dynamics simulations verified the synergistic effect of degradable plastics and bio-oil by the pyrolysis behavior in different systems and temperatures, and the pyrolysis pathways were proposed. This non-autocatalytic system realized the resource recovery and heavy bio-oil upgrading using an Fe/Ce OC.

Regulation strategy for nutrient-dependent carbon and nitrogen stoichiometric homeostasis in freshwater phytoplankton.

Phytoplankton carbon (C) and nitrogen (N) stoichiometric homeostasis plays an important role in aquatic ecosystems. Their C:N ratio is a result of cellular metabolic balance, and the relevant regulatory strategy for its plasticity is still unclear. Therefore, a field survey of seven reservoirs in Tianjin, North China, was conducted to understand variations in phytoplankton C:N ratios, and a laboratory culture of Chlamydomonas reinhardtii was performed to understand the relevant regulation strategy for cellular C-N stoichiometric homeostasis under different C and N availability by using transcriptome sequencing and Nano SIMS and C stable isotope analyses. The results indicated that CO2 limitation had no significant effect on the phytoplankton C:N ratio in either scene, whereas limitation of dissolved inorganic N induced a 35% higher ratio in the field and a 138% higher ratio in the laboratory. Under CO2 limitation, algal CO2-concentrating mechanisms were operated to ensure a C supply, and coupled C-N molecular regulation remained the cellular C:N ratio stable. Under nitrate limitation, differentially expressed gene-regulated intensities increase enormously, and their increasing proportion was comparable to that of the algal C:N ratio; cellular metabolism was reorganized to form a "subhealthy" C-N stoichiometric state with high C:N ratios. In addition, the N transport system had a specific role under CO2 and nitrate limitations. Our study implies that algal stoichiometric homeostasis depends on the involved limitation element and will help to deepen the understanding of C-N stoichiometric homeostasis in freshwater phytoplankton.

Pharmacodynamic Mechanism of Kuanxiong Aerosol for Vasodilation and Improvement of Myocardial Ischemia.

OBJECTIVE: To explore the effect of Kuanxiong Aerosol (KXA) on isoproterenol (ISO)-induced myocardial injury in rat models. METHODS: Totally 24 rats were radomly divided into control, ISO, KXA low-dose and high-dose groups according to the randomized block design method, and were administered by intragastric administration for 10 consecutive days, and on the 9th and 10th days, rats were injected with ISO for 2 consecutive days to construct an acute myocardial ischemia model to evaluate the improvement of myocardial ischemia by KXA. In addition, the diastolic effect of KXA on rat thoracic aorta and its regulation of ion channels were tested by in vitro vascular tension test. The influence of KXA on the expression of calcium-CaM-dependent protein kinase II (CaMK II)/extracellular regulated protein kinases (ERK) signaling pathway has also been tested. RESULTS: KXA significantly reduced the ISO-induced increase in ST-segment, interventricular septal thickness, cardiac mass index and cardiac tissue pathological changes in rats. Moreover, the relaxation of isolated thoracic arterial rings that had been precontracted using norepinephrine (NE) or potassium chloride (KCl) was increased after KXA treatment in an endothelium-independent manner, and was attenuated by preincubation with verapamil, but not with tetraethylammonium chloride, 4-aminopyridine, glibenclamide, or barium chloride. KXA pretreatment attenuated vasoconstriction induced by CaCl2 in Ca2+-free solutions containing K+ or NE. In addition, KXA pretreatment inhibited accumulation of Ca2+ in A7r5 cells mediated by KCl and NE and significantly decreased p-CaMK II and p-ERK levels. CONCLUSION: KXA may inhibit influx and release of calcium and activate the CaMK II/ERK signaling pathway to produce vasodilatory effects, thereby improving myocardial injury.

Huoxin Pill inhibits isoproterenol-induced transdifferentiation and collagen synthesis in cardiac fibroblasts through the TGF-ß/Smads pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The abnormal proliferation and differentiation of cardiac fibroblasts (CFs) are universally regarded as the key process for the progressive development of cardiac fibrosis following various cardiovascular diseases. Huoxin Pill (Concentrated pill, HXP) is a Chinese herbal formula for treating coronary heart disease. However, the cellular and molecular mechanisms of HXP in the treatment of myocardial fibrosis are still unclear. AIM OF THE STUDY: To investigate the effects of HXP on CFs transdifferentiation and collagen synthesis under isoproterenol (ISO) conditions, as well as the potential mechanism of action. MATERIALS AND METHODS: In vivo, we established a rat model of cardiac fibrosis induced by ISO, and administered with low or high dose of HXP (10 mg/kg/day or 30 mg/kg/day). The level of α-SMA was detected by immunohistochemistry examination, and combined with RNA-sequencing analysis to determine the protective effect of HXP on myocardial fibrosis rats. In vitro, by culturing primary rat CFs, we examined the effects of HXP on the proliferation and transdifferentiation of CFs using CCK8, scratch wound healing and immunofluorescence assays. Western blot was used to determine protein expression. RESULTS: The findings revealed that HXP protects against ISO-induced cardiac fibrosis and CFs transdifferentiation in rats. RNA-sequencing and pathway analyses demonstrated 238 or 295 differentially expressed genes (DEGs) and multiple enriched signal pathways, including transforming growth factor-beta (TGF-ß) receptor signaling activates Smads, downregulation of TGF-ß receptor signaling, signaling by TGF-ß receptor complex, and collagen formation under treatment with low or high-dose of HXP. Moreover, HXP also markedly inhibited ISO-induced primary rat CFs proliferation, transdifferentiation, collagen synthesis and the upregulation of TGF-ß1 and phosphorylated Smad2/3 protein expression. CONCLUSION: HXP suppresses ISO-induced CFs transdifferentiation and collagen synthesis, and it may exert these effects in part by inhibiting the activation of the TGF-ß/Smads pathway. This may be a new therapeutic tool for cardiac fibrosis.

Huoxin Pill () Attenuates Cardiac Fibrosis by Suppressing TGF-ß1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats.

OBJECTIVE: To evaluate the effects of Huoxin Pill (, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats. METHODS: Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor- ß 1 (TGF-ß 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western-blot assay. RESULTS: HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen I and collagen III protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-ß 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3. CONCLUSIONS: HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-ß 1/Smad2/3 pathway.

Kuanxiong aerosol inhibits apoptosis and attenuates isoproterenol-induced myocardial injury through the mitogen-activated protein kinase pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kuanxiong aerosol (KXA) is a common clinical drug based on Fangxiang Wentong (FXWT) therapy in the treatment of angina pectoris. However, the pharmacological mechanism of KXA in the prevention and treatment of myocardial injury (MI) is not clear. AIM OF THE STUDY: The purpose of this study was to explore the protective effect of KXA on isoproterenol (ISO)-induced MI in rats. MATERIALS AND METHODS: The study included male Wistar Kyoto rats (age: 6 weeks). The rats were randomly divided into the following 5 groups (n = 6 per group): control group, ISO group, isosorbide mononitrate (ISMN) group (5 mg/kg), KXA-L group (0.1 mL/kg), and KXA-H group (0.3 mL/kg). The rats in the last three groups were given intragastric administration for 14 days, and rats in control group and ISO group were given the same amount of normal saline daily. ISO (120 mg/kg) was used to induce MI on the 13th and 14th days. We assessed electrocardiograms (ECGs), myocardial specific enzymes, histopathological changes, and apoptosis. RESULTS: We found that KXA reduced the increase in the ST-segment amplitude (elevation or depression) and the levels of myocardial marker enzymes induced by ISO in MI rats, improved the pathological changes in myocardial tissue, and reduced cardiomyocyte apoptosis. At the same time, KXA significantly inhibited the up-regulation of caspase-3 and Bax expression and down-regulation of Bcl-2 expression induced by ISO. RNA sequencing showed that 90 up-regulated genes induced by ISO were down-regulated after KXA treatment, whereas 27 down-regulated genes induced by ISO were up-regulated after KXA treatment. In addition, KEGG pathway enrichment analysis showed that the mitogen-activated protein kinase (MAPK) signaling pathway may be an important target of KXA in the treatment of ISO-induced MI in rats. The results of RNA sequencing verified by Western blot analysis showed that KXA significantly inhibited the activation of the ISO-induced MAPK pathway. CONCLUSIONS: KXA improves cardiac function in MI rats by inhibiting apoptosis mediated by the MAPK signaling pathway.

Modulating AtDREB1C Expression Improves Drought Tolerance in Salvia miltiorrhiza.

Dehydration responsive element binding proteins are transcription factors of the plant-specific AP2 family, many of which contribute to abiotic stress responses in several plant species. We investigated the possibility of increasing drought tolerance in the traditional Chinese medicinal herb, Salvia miltiorrhiza, through modulating the transcriptional regulation of AtDREB1C in transgenic plants under the control of a constitutive (35S) or drought-inducible (RD29A) promoter. AtDREB1C transgenic S. miltiorrhiza plants showed increased survival under severe drought conditions compared to the non-transgenic wild-type (WT) control. However, transgenic plants with constitutive overexpression of AtDREB1C showed considerable dwarfing relative to WT. Physiological tests suggested that the higher chlorophyll content, photosynthetic capacity, and superoxide dismutase, peroxidase, and catalase activity in the transgenic plants enhanced plant drought stress resistance compared to WT. Transcriptome analysis of S. miltiorrhiza following drought stress identified a number of differentially expressed genes (DEGs) between the AtDREB1C transgenic lines and WT. These DEGs are involved in photosynthesis, plant hormone signal transduction, phenylpropanoid biosynthesis, ribosome, starch and sucrose metabolism, and other metabolic pathways. The modified pathways involved in plant hormone signaling are thought to be one of the main causes of the increased drought tolerance of AtDREB1C transgenic S. miltiorrhiza plants.

γ-Tocotrienol protects against ovariectomy-induced bone loss via mevalonate pathway as HMG-CoA reductase inhibitor.

γ-Tocotrienol (GT3), an analogue of vitamin E, has gained increasing scientific interest recently as it provides significant health benefits. GT3 exerts its biological effects not only by virtue of antioxidant properties but also by inhibiting hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Studies have reported that the mevalonate pathway is relevant for bone metabolism and HMG-CoA reductase inhibitors can increase bone mass and are useful in osteoporosis therapy. However, whether it is involved in the bone anabolic activity of GT3 is not clear. This study was conducted to investigate the ability of GT3 to protect against ovariectomy-induced bone loss, as well as the correlation between the protections and mevalonate pathway. Results showed that mice supplemented with 100mg/kg emulsified GT3 via subcutaneous injection once per month for three months were significantly protected from ovariectomy-induced bone loss as evaluated by various bone structural parameters, bone metabolic gene expression levels and serum levels of biochemical markers for bone resorption and bone formation. Importantly, the effect of GT3 on preventing against ovariectomy-induced bone loss could be reversed by daily supplementation with mevalonate, indicating that GT3 may via an HMG-CoA reductase-dependent mechanism to protect against ovariectomy-induced bone loss. Our results suggest that GT3 is suitable as dietary supplement and has potential as an alternative drug to treat or prevent osteoporosis.

Treatment of porcine donor cells and reconstructed embryos with the antioxidant melatonin enhances cloning efficiency.

This study was conducted to investigate the effect of melatonin during the culture of donor cells and cloned embryos on the in vitro developmental competence and quality of cloned porcine embryos. At concentrations of 10(-6 )M or 10(-8) M, melatonin significantly enhanced the proliferation of porcine fetal fibroblasts (PFFs), and the blastocyst rate was significantly increased in the 10(-10) M melatonin-treated donor cell group. Cloned embryo development was also improved in embryo culture medium that was supplemented with 10(-9) M or 10(-12) M melatonin. When both donor cells and cloned embryos were treated with melatonin, the cleavage rate and total cell number of blastocysts were not significantly affected; however, the blastocyst rate was increased significantly (20.0% versus 11.7%). TUNEL assays showed that combined melatonin treatment reduced the rate of apoptotic nuclei (3.6% versus 6.1%). Gene expression analysis of the apoptosis-related genes BAX, BCL2L1, and p53 showed that the expression of BCL2L1 was significantly elevated 2.7-fold relative to the control group, while the expression of BAX and p53 was significantly decreased by 3.7-fold and 23.2-fold, respectively. In addition, we detected the expression of two melatonin receptors (MT1 and MT2) in PFFs but not in porcine cloned embryos. We conclude that exogenous melatonin enhances the development of porcine cloned embryos and improves embryo quality by inhibiting p53-mediated apoptotic pathway. The proliferation of PFFs may be mediated by receptor binding, but the beneficial effects of melatonin on embryonic development may be receptor-independent, possibly through melatonin's ability to directly scavenge free radicals.

[Effect of oxymatrine on JAK2/STAT3 signaling in renal tissues of rats with septic shock].

OBJECTIVE: To explore the effect of oxymatrine (OMT) on JAK2/STAT3 signaling in renal tissues of rats with septic shock. METHOD: The cecal ligation and puncture (CLP) was adopted to establish the rat septic shock model. Fifty-six male SD rats were randomly divided into 7 groups: the sham operation group, the model (CLP) group, CLP + OMT high, middle, low-dose (52, 26, 13 mg x kg(-1), vena caudalis bolus) groups and the positive control (CLP + dexamethasone, 10 mg x kg(-1)) group. The pathological changes in renal tissues were examined with lightmicroscope. BUN content was determined by urine enzymatic method. Expressions of tumournecrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA in renal tissues were determined by RT-PCR. Expression of JAK2 and STAT3 in renal tissues determined by Western blot. Changes in tumournecrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) contents in renal tissue were determined by radioimmunoassay. RESULT: OMT of different doses could inhibit the JAK2 and STAT3 activation in renal tissues (P<0.05), and decrease the protein expression of JAK2, STAT3, TNF-alpha and IL-1beta mRNA (P<0.05). Besides, it could reduce TNF-alpha and IL-1beta contents in renal tissue homogenate (P<0.05), serum BUN content (P<0.05), and improve such lesions as tissue hyperemia, edema and inflammatory cell infiltration, with identical results in medium and high-dose OMT groups, and the positive control group. CONCLUSION: OMT can inhibit JAK2/STAT3 signaling activity to reduce the expression of proin-flammatory factors (TNF-alpha, IL-1beta) and treat the renal injury in rats with septic shock.

[Effects of Peristrophe roxburghiana on blood pressure. NO and ET in renal hypertensive rats].

OBJECTIVE: To observe the effects of Peristrophe roxbrughiana (HSX) on blood pressure, NO, No-synthase and ET in the serum and NO in urine in renal hypertensive rats. METHODS: The 2K1C(2 kidney 1 clap) hypertensive model rats were used and drugs had been given by ig. for 4 weeks. The blood pressure was measured at the end of the each week. At the end of 4th week, the urine was collected and the concentration of NO in the serum or urine, NO-synthease and ET in the serum were measured. RESULTS: HSX (H or L dosage) by ig. for 1 week can significantly lower the blood pressure, increase the levels of NO and NO-synthase in the serum and NO in the urine, reduce the concentration of ET in the serum. The effects have lasted for 4 weeks. CONCLUSION: HSX played an important role in the renal hypertensive rats.

Free radical scavenging properties of sulfinpyrazone.

Sulfinpyrazone, a potent uricosuric drug, was tested in vitro for its scavenging action against oxygen free radicals. In this study, sulfinpyrazone was able to scavenge 1,1-diphenyl-2-picrylhydrazyl radical with IC50 value of 29.82 micrograms/ml compared to butylated hydroxytoluene (BHT, IC50 value = 20.15 micrograms/ml) and Trolox (IC50 value = 16.01 micrograms/ml). It was able to scavenge superoxide anion with IC50 value of 27.72 micrograms/ml compared to Trolox (IC50 value = 22.08 micrograms/ml) and ascorbic acid (IC50 value = 14.65 micrograms/ml). The hydroxyl radical scavenging activity of sulfinpyrazone is in a concentration-dependent fashion. In the range of concentrations used, sulfinpyrazone was not a scavenger toward H2O2. However, the intracellular H2O2-induced 2',7'-dichlorofluorescin diacetate (DCF-DA) fluorescence in HL-60 cells was significantly reduced by sulfinpyrazone during 30-60 min of incubation. Finally, phorbol-12-myristate-13-acetate induced-lucigenin chemiluminescence in whole blood was markedly inhibited by sulfinpyrazone. Our results suggest a new direction for the pharmacological actions of sulfinpyrazone in free radical scavenging properties.

[Effect of the extract from Peristrophe roxburghiana on hemorheology in rats].

OBJECTIVE: To observe the effect of extract from Peristrophe roxburghiana (EPR) on the hemorheology and thrombosis in rats. METHODS: To study the hemorheology by adrenaline and ice-water stimulant and to observe thrombosis by the carotid and jugular bypath. RESULTS: EPR could effectively decrease many hemorheologic parameters in hypostasis rats and reduce the wet weight of thrombosis. CONCLUSIONS: EPR can improve the hemorheological parameters and inhibit the formation of thrombosis.