Bergenin alleviates proliferative arterial diseases by modulating glucose metabolism in vascular smooth muscle cells.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation and phenotypic switching are key mechanisms in the development of proliferative arterial diseases. Notably, reprogramming of the glucose metabolism pattern in VSMCs plays an important role in this process. PURPOSE: The aim of this study is to investigate the therapeutic potential and the mechanism underlying the effect of bergenin, an active compound found in Bergenia, in proliferative arterial diseases. METHODS: The effect of bergenin on proliferative arterial disease was evaluated using platelet-derived growth factor (PDGF)-stimulated VSMCs and a mouse model of carotid artery ligation. VSMC proliferation and phenotypic switching were evaluated in vitro using cell counting kit-8, 5-ethynyl-2-deoxyuridine incorporation, scratch, and transwell assays. Carotid artery neointimal hyperplasia was evaluated in vivo using hematoxylin and eosin staining and immunofluorescence. The expression of proliferation and VSMC contractile phenotype markers was evaluated using PCR and western blotting. RESULTS: Bergenin treatment inhibited PDGF-induced VSMC proliferation and phenotypic switching and reduced neointimal hyperplasia in the carotid artery ligation model. Additionally, bergenin partially reversed the PDGF-induced Warburg-like glucose metabolism pattern in VSMCs. RNA-sequencing data revealed that bergenin treatment significantly upregulated Ndufs2, an essential subunit of mitochondrial complex I. Ndufs2 knockdown attenuated the inhibitory effect of bergenin on PDGF-induced VSMC proliferation and phenotypic switching, and suppressed neointimal hyperplasia in vivo. Conversely, Ndufs2 overexpression enhanced the protective effect of bergenin. Moreover, Ndufs2 knockdown abrogated the effects of bergenin on the regulation of glucose metabolism in VSMCs. CONCLUSION: These findings suggest that bergenin is effective in alleviating proliferative arterial diseases. The reversal of the Warburg-like glucose metabolism pattern in VSMCs during proliferation and phenotypic switching may underlie this therapeutic mechanism.

Techno-economic assessment of hydrotreated vegetable oil as a renewable fuel from waste sludge palm oil.

To date, the development of renewable fuels has become a normal phenomenon to solve the problem of diesel fuel emissions and the scarcity of fossil fuels. Biodiesel production has some limitations, such as two-step processes requiring high free fatty acids (FFAs), oil feedstocks and gum formation. Hydrotreated vegetable oil (HVO) is a newly developed international renewable diesel that uses renewable feedstocks via the hydrotreatment process. Unlike FAME, FFAs percentage doesn't affect the HVO production and sustains a higher yield. The improved characteristics of HVO, such as a higher cetane value, better cold flow properties, lower emissions and excellent oxidation stability for storage, stand out from FAME biodiesel. Moreover, HVO is a hydrocarbon without oxygen content, but FAME is an ester with 11% oxygen content which makes it differ in oxidation stability. Waste sludge palm oil (SPO), an abundant non-edible industrial waste, was reused and selected as the feedstock for HVO production. Techno-economical and energy analyses were conducted for HVO production using Aspen HYSYS with a plant capacity of 25,000 kg/h. Alternatively, hydrogen has been recycled to reduce the hydrogen feed. With a capital investment of RM 65.86 million and an annual production cost of RM 332.56 million, the base case of the SPO-HVO production process was more desirable after consideration of all economic indicators and HVO purity. The base case of SPO-HVO production could achieve a return on investment (ROI) of 89.03% with a payback period (PBP) of 1.68 years. The SPO-HVO production in this study has observed a reduction in the primary greenhouse gas, carbon dioxide (CO2) emission by up to 90% and the total annual production cost by nearly RM 450 million. Therefore, SPO-HVO production is a potential and alternative process to produce biobased diesel fuels with waste oil.

Modified biochar/humic substance/fertiliser compound soil conditioner for highly efficient improvement of soil fertility and heavy metals remediation in acidic soils.

Fertile and uncontaminated soil with appropriate pH is crucial in terms of the agricultural sustainable development. Herein, a compound soil conditioner containing chitosan modified straw biochar (CBC), kitchen waste compost product-derived humic substance (HS), NPK compound fertiliser (NPK-CF) was prepared to simultaneously adjust acidic soil pH, improve fertility, and immobilize heavy metal. The results exhibited that the best Pb and NH4+ adsorption performance was obtained in CBC with chitosan:biochar of 1:5. Then, the acid soil pH was improved from 5.03 to 6.66 in the presence of CBC/HS (5:5) with 3% addition weight (the mass ratio of conditioner to soil). Meanwhile, compared with the control, the contents of organic matter, available nitrogen, and available phosphorus significantly increased by 52.4%, 92.6%, and 136.3%, respectively. Moreover, Pb was highly efficient immobilised by CBC, and the concentration of Pb in the soil was decreased by 55.2%. The optimal growth trend of ryegrass was obtained in the presence of 3% addition weight (the mass ratio of conditioner to soil) CBC/HS (CBC:HS = 5:5) combined with 60% of the recommended NPK-CF application weight, which was mainly contributed by the improvement of the soil microbial abundance and community structure diversity. The addition of CBC/HS could effectively reduce the addition of NPK-CF and contribute to simultaneous controlling nitrogen loss, releasing phosphorus, immobilising Pb, adjusting pH, improving soil quality and controlling nonpoint pollution.

Acupotomy combined with intra-articular injection of sodium hyaluronate in the treatment of knee osteoarthritis.

This retrospective study aimed to compare the effects of acupotomy combined with intra-articular injection of sodium hyaluronate (IA-SH) for the treatment of knee osteoarthritis (KOA). Eighty electronic medical records of patients with KOA were retrospectively analyzed. The patients were divided into an intervention group (n = 40, acupotomy plus IA-SH) and a control group (n = 40, IA-SH). Outcome measures included the visual analog scale, the Western Ontario and McMaster Universities Arthritis Index (WOMAC), and adverse events. Outcome data were collected and analyzed before and after treatment. The results of this study showed that there was a greater reduction in the visual analog scale (P < .01) and WOMAC scores (pain, P < .01; stiffness, P < .01; function, P < .01; total, P < .01) in the intervention group than in the control group. In addition, there were no significant differences in adverse events between the 2 groups. In this study, the effects of acupotomy plus IA-SH were superior to those of IA-SH alone for the treatment of patients with KOA. Further prospective studies are required to confirm these findings.

[Effect of intercropping with Vicia faba on secondary metabolites and rhizosphere soil microbial diversity of Notopterygium incisum].

Rhizosphere soil microbial community and its diversity are important for the structure and functions of medicinal plant ecosystem. In this study, based on high-throughput sequencing, rhizosphere soil microbial diversity, and yield and quality of rhizome and root of Notopterygium incisum cultivated alone(control, CK) and intercropped with Vicia faba(QH) were analyzed, which is expected to lay a basis for optimization of the cultivation mode and ecological production of N. incisum. RESULTS:: showed that the rhizosphere soil bacteria of N. incisum were dominated by Proteobacteria and Bacteroides, with the relative abundance of 50.38%-51.95% and 16.36%-17.02%, respectively. Soil bacterial community at the phylum level was not significantly different between CK and QH. At the genus level, the relative abundance of MND1(3.54%), Spinstomonas(3.50%), Nitrospira(1.53%), and Rhizobacter(1.05%) was significantly higher and that of Gemmatimonas, Candidatus＿Solibacter, and Bryophytes was lower in QH treatment than in the CK. The plant height, leaf length, leaf width, and petiole length of N. incisum in QH treatment was significantly increased and the underground biomass rose by 71.43% compared with those in the CK. Thus, intercropping with V. faba promoted the aboveground growth of N. incisum and improved the yield of root and rhizome. Moreover, the content of notopterol and isoimperatorin increased by 37.96% and 4.09% in QH treatment, respectively, indicating that the intercropping with V. faba boosted the accumulation of secondary metabolites in N. incisum. Pearson's correlation analysis showed that the soil bacterial community was mainly influenced by the soil factors including the content of soil available nutrients, soil organic matter, pH value, and soil water. The influence was in the order: total potassium>total nitrogen>pH>organic matter>available potassium>soil water content>available nitrogen>available phosphorus. In conclusion, the intercropping with V. faba altered soil microenvironment and also increased the yield and accumulation of secondary metabolites of N. incisum, which is a promising ecological planting model for N. incisum.

Recent progress on in-situ chemical oxidation for the remediation of petroleum contaminated soil and groundwater.

Accidental oil leaks and spills can often result in severe soil and groundwater pollution. In situ chemical oxidation (ISCO) is a powerful and efficient remediation technology. In this review, the applications and recent advances of three commonly applied in-situ oxidants (hydrogen peroxide, persulfate, and permanganate), and the gap in remediation efficiency between lab-scale and field-scale applications is critically assessed. Feasible improvements for these measures, especially solutions for the 'rebound effect', are discussed. The removal efficiencies reported in 108 research articles related to petroleum-contaminated soil and groundwater were analyzed. The average remediation efficiency of groundwater (82.7%) by the three oxidants was higher than that of soil (65.8%). A number of factors, including non-aqueous phase liquids, adsorption effect, the aging process of contaminants, low-permeability zones, and vapor migration resulted in a decrease in the remediation efficiency and caused the residual contaminants to rebound from 19.1% of the original content to 57.7%. However, the average remediation efficiency of ISCO can be increased from 40.9% to 75.5% when combined with other techniques. In the future, improving the utilization efficiency of reactive species and enhancing the contact efficiency between oxidants and petroleum contaminants will be worthy of attention. Multi-technical combinations, such as the ISCO coupled with phase-transfer, viscosity control, controlled release or natural attenuation, can be effective methods to solve the rebound problem.

Comparison of norepinephrine, dopamine and dobutamine combined with enteral nutrition in the treatment of elderly patients harboring sepsis.

The present study was performed in order to investigate the safety and efficacy of different vasoactive drugs combined with enteral nutrition in terms of treating elderly patients with sepsis. A total of 75 elderly patients with sepsis treated with enteral nutrition in our hospital were randomly divided into three groups: group A (n = 25), group B (n = 25) and group C (n = 25). The three groups were treated with dopamine, dobutamine and norepinephrine respectively. One week after treatment, the therapeutic effects of the three groups were compared, the vascular elastic indexes, hemodynamic indexes and levels of inflammatory factors of the three groups were measured. After treatment, the clinical effective rate of group C was evidently higher than that of group A and group B. The vascular elasticity coefficient and stiffness coefficient in group C were significantly lower than those in group A and group B, and the arterial compliance in group C was significantly higher than that in group A and group B (P < 0.05). The levels of MAP and PVRI in group C were significantly higher than those in group A and B, and the levels of CI, CVP and HR in group C were significantly lower than those in group A and group B (P < 0.05). Norepinephrine elicited greater effects in terms of improving hemodynamic indexes, vascular elasticity and reducing the level of inflammatory factors compared with dopamine and dobutamine in elderly patients harboring sepsis.

K-strategy species plays a pivotal role in the natural attenuation of petroleum hydrocarbon pollution in aquifers.

The natural attenuation of petroleum hydrocarbons is inseparable from the action of microorganisms, while the degradation methods and ecological strategies of microorganisms in petroleum-contaminated aquifers are still under debate. In the present study, 16 S rRNA sequencing and quantitative real-time polymerase chain reaction were used to assess the potential microbial degradation of petroleum hydrocarbons, and the ecological strategy of microorganisms under petroleum stress was analyzed through a co-occurrence network. The results showed that the microbial community in sediments exhibit higher efficiency and stability and stronger ecological function than that in groundwater. Keystone species coordinated with the community to execute ecosystem processes and tended to choose a K-strategy to survive, with the aquifer sediment being the main site of petroleum hydrocarbon degradation. Under natural conditions, the presence of petroleum hydrocarbons at concentrations higher than 126 µg kg-1 and 5557 µg kg-1 was not conducive to the microbial degradation of polycyclic aromatic hydrocarbons and alkanes, respectively. These results can be used as a reference for an enhanced bioremediation of contaminated groundwater. Overall, these findings provide support to managers for developing environmental management strategies.

Efficacy and safety of two different adjuvant chemotherapy regimens in combination with concurrent chemoradiotherapy in treating patients with advanced nasopharyngeal carcinoma: A protocol for randomized controlled trial.

BACKGROUND: Concurrent chemoradiotherapy is widely utilised as a standardized primary method of treatment for patients with advanced nasopharyngeal carcinoma (NPC). However, the combination of concurrent chemoradiotherapy and adjuvant chemotherapy for treating NPC patients remain unclear. Therefore, this study attempts to elucidate the efficiency and safety of concurrent chemoradiotherapy combined with adjuvant chemotherapy (gemcitabine plus cisplatin versus 5-fluorouracil plus cisplatin) for treating patients with NPC. MATERIALS AND METHODS: This study is a randomized, multicentral, open-labelled trial to assess the clinical efficiency and safety of using concurrent chemoradiotherapy combined with adjuvant chemotherapy as a therapeutic measure for advanced NPC patients. A total of 50 patients will be randomly assigned into 2 groups, namely treatment-group-one and treatment-group-two. Eligible patients will be administered with concurrent chemoradiotherapy and subsequentially with adjuvant chemotherapy (gemcitabine plus cisplatin or 5-fluorouracil plus cisplatin). Moreover, the primary endpoint is a comparison of progression-free survival between concurrent chemoradiotherapy and subsequentially adjuvant gemcitabine and cisplatin and chemoradiotherapy, which is proceeded by adjuvant 5-fluorouracil and cisplatin in advanced NPC patients. Overall survival, overall response rate, incidence of acute and late toxicity, and adverse events are the minor endpoints. Statistical analyses will be performed with SPSS 25.0 software. DISCUSSION: The current research evaluates the clinical efficiency and safety of utilising concurrent chemoradiotherapy combined with adjuvant chemotherapy as a therapeutic strategy to treat advanced NPC patients. The work done in this study will provide a clinical basis for concurrent chemoradiotherapy in combination with adjuvant chemotherapy for treating advanced NPC. TRIAL REGISTRATION: DOI 10.17605/OSF.IO/5UPVM.

Acquired segmental sigmoid hypoganglionosis: A case report.

RATIONALE: Intestinal hypoganglionosis most commonly presents in infancy or childhood, with only a few cases reported in adults. Those are mainly diagnosed after elective surgery for long-standing constipation and megacolon. PATIENT CONCERNS: We report a case of a 48-year-old female from China who presented with symptoms of discontinuation of bowel movements for 2 months. A hard, round mass could be felt in her right lower abdomen. DIAGNOSIS: The following examination methods diagnosed acquired segmental sigmoid hypoganglionosis. An abdominal computed tomography revealed a dilatation of the colon and suspicious wall thickening of the sigmoid colon. Anorectal manometry revealed relaxation of the anal sphincter. Histological examination revealed lower numbers and the degeneration of ganglion cells. INTERVENTIONS: Sigmoidectomy and transverse colostomy. OUTCOMES: The patient recovered well from surgery. Three months after the surgery, barium enema revealed a recovery in colorectal dilatation. LESSONS: This case could help raise awareness of acquired segmental hypoganglionosis. Resection of TZ and enterostomy presents an effective remission strategy for patients at risk of anastomotic leakage due to poor intestinal conditions.

A Tomato Nucleotide Binding Sites-Leucine-Rich Repeat Gene Is Positively Involved in Plant Resistance to Phytophthora infestans.

The nucleotide binding sites-leucine-rich repeat (NBS-LRR) genes are key regulatory components of plant to pathogens. Phytophthora infestans-inducible coding sequence encoding an NBS-LRR (SpNBS-LRR) protein in tomato (Solanum pimpinellifolium L3708) was cloned and characterized based on our RNA-Seq data and tomato genome. After sequence analysis, SpNBS-LRR was identified as a hydrophilic protein with no transmembrane topological structure and no signal peptide. SpNBS-LRR had a close genetic relationship to RPS2 of Arabidopsis thaliana by phylogenetic analysis. In addition, SpNBS-LRR gene was mainly expressed in root, with low expression observed in leaf and stem. To further investigate the role of SpNBS-LRR in tomato-P. infestans interaction, SpNBS-LRR was introduced in susceptible tomatoes and three transgenic lines with higher expression level of SpNBS-LRR were selected. These transgenic tomato plants that overexpressed SpNBS-LRR displayed greater resistance than wild-type tomato plants after infection with P. infestans, as shown by decreased disease index, lesion diameters, number of necrotic cells, P. infestans abundance, and higher expression levels of the defense-related genes. This information provides insight into SpNBS-LRR involved in the resistance of tomato to P. infestans infection and candidate for breeding to enhance biotic stress-resistance in tomato.

Granulation of drinking water treatment residuals as applicable media for phosphorus removal.

Recycling drinking water treatment residuals (DWTR) show promise as a strategy for phosphorus (P) removal; however, powdered DWTR is not an ideal practical medium due to clogging. This study granulates DWTR by entrapping powdered DWTR in alginate beads. Results show that granular DWTR has an appreciable amount of mesopores along with a Brunauer-Emmett-Teller (BET) surface area of 43.8 m2/g and total pore volume of 0.049 cm3/g. Most metals (e.g., Al, Ba, Be, Cd, Co, Cr, Mn, Ni, Pb, and Zn) in granular DWTR became more stable and granular DWTR could be considered non-hazardous material. Further analysis indicates that the granular DWTR has strong P adsorption capability with a maximum adsorption capacity of 19.70 mg/g as estimated by the Langmuir model. Good P adsorption may be attributed to the formation of Fe-PO4 and Al-PO4 associated with the amorphous state of enormous iron and aluminum in granular DWTR. More importantly, granular DWTR exhibits good mechanical stability and maintained its shape with weight loss below 12.49% after three recycling rounds. Overall, granular DWTR appears to serve as better media for phosphorus removal in water treatment structures such as wetlands.

Reclamation history and development intensity determine soil and vegetation characteristics on developed coasts.

The question of where and how to carry out reclamation work in coastal areas is still not well addressed in coastal research. To answer the question, it is essential to quantify the impact of reclamation and the associated ecological and/or environmental responses. In this study, ordinary least square (OLS) analysis and geographical weighted regression (GWR) analysis were performed to identify the reclamation variables that affect soil and vegetation characteristics. Reclamation related variables, including residential population (RP), years of reclamation (YR), income per capita (IP), and land use-based human impact index (HII), were used to explain nitrate, ammonium, total phosphorous, and heavy metals in soil, and the height, density, and above-ground biomass of native hydrophytic vegetation. It was found that variables IP, RP, and HII could be used to explain the height of Scirpus and Phragmites australis as well as above-ground biomass with a R2 value of no >0.55, and almost all the variables could explain the hydrophytic vegetation characteristics with a higher R2 value. In comparison to OLS, GWR more reliably reflected the reclamation effects on soil and vegetation characteristics. By GWR analysis, total soil phosphorous, and nitrate and ammonium nitrogen could be explained by RP, YR, and HII, with the highest Ad-R2 value of 0.496, 0.631 and 0.632, respectively. Both of the GWR and OLS analysis revealed that HII and RP were the better variables for explaining the soil and vegetation characteristics. This work demonstrated that coastal reclamation was highly spatial dependent, which sheds a light on the future development of spatial explicit and process-based models to guide coastal reclamation around the world.

Cytotoxic Compounds from Juglans sinensis Dode Display Anti-Proliferative Activity by Inducing Apoptosis in Human Cancer Cells.

Phytochemical investigation of the bark of Juglans sinensis Dode (Juglandaceae) led to the isolation of two active compounds, 8-hydroxy-2-methoxy-1,4-naphthoquinone (1) and 5-hydroxy-2-methoxy-1,4-naphthoquinone (2), together with 15 known compounds 3-17. All compounds were isolated from this plant for the first time. The structures of 1 and 2 were elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments. Compounds 1-17 were tested for their cytotoxicity against the A549 human lung cancer cell line; compounds 1 and 2 exhibited significant cytotoxicity and additionally had potent cytotoxicity against six human cancer cell lines, MCF7 (breast cancer), SNU423 (liver cancer), SH-SY5Y (neuroblastoma), HeLa (cervical cancer), HCT116 (colorectal cancer), and A549 (lung cancer). In particular, breast, colon, and lung cancer cells were more sensitive to the treatment using compound 1. In addition, compounds 1 and 2 showed strong cytotoxic activity towards human breast cancer cells MCF7, HS578T, and T47D, but not towards MCF10A normal-like breast cells. They also inhibited the colony formation of MCF7, A549, and HCT116 cells in a dose-dependent manner. Flow cytometry analysis revealed that the percentage of apoptotic cells significantly increased in MCF7 cells upon the treatment with compounds 1 and 2. The mechanism of cell death caused by compounds 1 and 2 may be attributed to the upregulation of Bax and downregulation of Bcl2. These findings suggest that compounds 1 and 2 may be regarded as potential therapeutic agents against cancer.

Application prospect and clinical effect analysis of Fu Chan Xue Jing during bleeding after abortion.

To investigate the application future of Fu Chan Xue Jing during bleeding after abortion and to observe the clinical effect analysis of Fu Chan Xue Jing on the treatment of bleeding after medical abortion. 86 patients who were willing to perform medical abortion in Women and infants Hospital of Zhengzhou from December 2013 to November 2014 were randomly divided into two groups, with 43 cases in either observation group or control group. Basic medical abortion was conducted on the patients in control group, apart from which Fu Chan Xue Jing was added on the patients in observation group. Meanwhile, the vaginal bleeding volume and vaginal bleeding time for patients in both groups were observed and compared. The treatment results showed that the vaginal bleeding volume for patients in treatment group was lower than that in control group, showing statistically significant difference (P<0.05); the average time (7.5 ± 1.3 d) of vaginal bleeding for patients in treatment group was shorter than that (13.5 ± 4.1d) in control group, showing statistically significant difference for the data of the two groups (P<0.05). Fu Chan Xue Jing is conducive to reduce the bleeding after abortion and help to recovery the normal menstruation faster, which has good effects to prevent the bleeding volume after medical abortion and control the bleeding time, worth popularizing on clinic.

COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells.

The expansion of myeloid-derived suppressor cells (MDSCs) is a common feature of cancer, but its biological roles and molecular mechanism remain unclear. Here, we investigated a molecular link between MDSC expansion and tumor cell metastasis in nasopharyngeal carcinoma (NPC). We demonstrated that MDSCs expanded and were positively correlated with the elevated tumor COX-2 expression and serum IL-6 levels in NPC patients. Importantly, COX-2 and MDSCs were poor predictors of patient disease-free survival (DFS). Knocking down tumor COX-2 expression hampered functional TW03-mediated-MDSC cell (T-MDSC) induction with IL-6 blocking. We identified that T-MDSCs promoted NPC cell migration and invasion by triggering the epithelial-mesenchymal transition (EMT) on cell-to-cell contact, and T-MDSCs enhanced tumor experimental lung metastasis in vivo. Interestingly, the contact between T-MDSCs and NPC cells enhanced tumor COX-2 expression, which subsequently activated the ß-catenin/TCF4 pathway, resulting in EMT of the cancer cells. Blocking transforming growth factor ß (TGFß) or inducible nitric oxide synthase (iNOS) significantly abolished the T-MDSC-induced upregulation of COX-2 and EMT scores in NPC cells, whereas the administration of TGFß or L-arginine supplements upregulated COX-2 expression and EMT scores in NPC cells. These findings reveal that COX-2 is a key factor mediating the interaction between MDSCs and tumor cells, suggesting that the inhibition of COX-2 or MDSCs has the potential to suppress NPC metastasis.

Apios americana Medik Extract Alleviates Lung Inflammation in Influenza Virus H1N1- and Endotoxin-Induced Acute Lung Injury.

Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

A pharmacodynamic simulation to evaluate tigecycline in treatment of nosocomial pneumonia caused by multidrug-resistant Acinetobacter baumannii.

The shortage of effective antibiotics against multidrug-resistant Acinetobacter baumannii (MDR-Ab) has posed great threat to the public health. But the advent of tigecycline gives us new hope. The goal of our research was to assess the clinical efficacy of tigecycline at different doses by using a pharmacokinetic/pharmacodynamic (PK/PD) model which can incorporate pharmacokinetic data of tigecycline from patients with pneumonia and MICs of MDR-Ab from a tertiary hospital. A 10000-patient Monte-Carlo Simulation based on the PK/PD model was conducted to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of tigecycline. 97% isolates displayed susceptibility and 3% were tigecycline-intermediate strains and the values of MIC ranged from 0.125 to 4 µ g/ml. A CFR of 61.62% was predicted for tigecycline at current dosage (50 mg q12h). When the dosage was increased, the predicted CFRs for 75 mg q12h, 100 mg q12h, 125 mg q12h, 150 mg q12h were 81.00%, 89.86%, and 94.57%, 96.77%, respectively. Despite presented higher susceptibility, the CFR obtained was not optimal at current dosage. A higher CFR indicating a better clinical efficacy can be gained by the increased dosage.

Molecular cloning, characterization and expression analysis of melanotransferrin from the sea cucumber Apostichopus japonicus.

Melanotransferrin (MTf), a member of the transferrin families, plays an important role in immune response. But the research about MTf in sea cucumber is limited till now. In this study, the Melanotransferrin (Aj-MTf) gene was firstly cloned and characterized from the sea cucumber Apostichoupus japonicus by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends. The full-length cDNA of Aj-MTf is 2,840 bp in length and contains a 2,184 bp open reading frame that encodes a polypeptide of 727 amino acids. An iron-responsive element-like structure is located at the 5'-UTR of Aj-MTf cDNA. Sequence analysis shows that the Aj-MTf contains two conserved domains, and the binding-iron (III) sites, including eight amino acid residues (D81,Y109,Y215,H283,D425,Y454,Y565 and H634) and three N-linked glycosylation sites (N121V122S123,N173A174S175 and N673S674T675). Quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested that the Aj-MTf expressions in the coelomic fluid, body cavity wall and respiratory trees were significantly changed from 4 to 24 h post lipopolysaccharide (LPS) injection. The mRNA levels of Aj-MTf in coelomic fluid was significantly up-regulated at 12 and 24 h in treatment group, and Aj-MTf shared a similar expression pattern with C-type lectin in coelomic fluid, while both genes appears to gradually increase after 4 h of LPS injection. These results indicate that the Aj-MTf plays a pivotal role in immune responses to the LPS challenge in sea cucumber, and provide new information that it is complementary to the sea cucumber immune genes and initiate new researches concerning the genetic basis of the holothurian immune response.

Oridonin induces apoptosis in SW1990 pancreatic cancer cells via p53- and caspase-dependent induction of p38 MAPK.

Oridonin, an active component isolated from Rabdosia rubescens, has been reported to exhibit antitumor effects. In the present study, we evaluated the antitumor activity and the mechanisms of action of oridonin in pancreatic cancer. Oridonin treatment significantly induced apoptotic cell death in SW1990 pancreatic cancer cells in a dose-dependent manner. Additionally, cell apoptosis was markedly inhibited by PFT α (pifithrin α), a p53-specific inhibitor, which was applied to evaluate the function of p53, showing that p53 was responsible for the cytotoxity of oridonin. Moreover, oridonin increased the expression of p-p53 with a concomitant increase in p21 in the SW1990 cells. Following treatment with mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor), the cytotoxity of oridonin was not influenced by JNK (SP600125) and ERK (PD98059), but these effects were opposite to the cytotoxity of oridonin observed with SP203580 treatment. These findings confirmed that orodonin-induced apoptosis was p38-dependent, but JNK- and ERK-independent. Furthermore, the activation of the p38 kinase promoted the activation of p53 and its downstream target p21, and further caused caspase-9 and -3 activation, as demonstrated by evidence showing that the p38 inhibitor SB203580 not only blocked the phosphorylation of p38 but also reduced the activation of p53, p21 and caspase-9 and -3. Collectively, these results suggest that p53-dependent and caspase-dependent induction of p38 MAPK directly participates in apoptosis induced by oridonin.