Intraoperative blood auto-transfusion restrained the malignancy of Liver Cancer via regulating functions of tumor cells and Kuffer cells.

The role of IBA in regulating the recovery of liver cancer was investigated using a rat model of liver cancer and an intraoperative blood return model (IBA). SD rats were used to construct the IBA model. Kupffer cells were isolated from liver cancer tissues, and their biological characteristics were analyzed by flow cytometry. Comet assay was used to detect DNA damage in tumor cells; clone formation assay and transwell assay were used to detect tumor cell proliferation and migration ability. Western blot analysis was used to determine the changes in related signaling pathways. After the IBA treatment, the production of KCs was significantly promoted in rat liver cancer tissues, and the expression levels of cell cycle arrest proteins P53, AEN and CDKN1A were also significantly increased. In tumor cells, IBA induced cell cycle arrest and cellular DNA damage in a p53-mediated manner. In addition, the proliferation and migration of cancer cells were also significantly inhibited. Similar to the in vivo data, the expression of TP53, AEN and CDKN1A was also up-regulated. Our study showed that IBA can inhibit the malignant transformation of hepatocellular carcinoma by modulating the function-dependent p53-mediated pathway of tumor cells and KCs.

Co-exposure of sulfur nanoparticles and Cu alleviate Cu stress and toxicity to oilseed rape Brassica napus L.

Experiments were performed to explore the impact of sulfur nanoparticles (SNPs) on growth, Cu accumulation, and physiological and biochemical responses of oilseed rape (Brassica napus L.) inoculated with 5 mg/L Cu-amended MS medium supplemented with or without 300 mg/L SNPs exposure. Cu exerted severe phytotoxicity and inhibited plant growth. SNPs application enhanced the shoot height, root length, and dry weight of shoot and root by 34.6%, 282%, 41.7% and 37.1%, respectively, over Cu treatment alone, while the shoot and root Cu contents and Cu-induced lipid perodixation as the malondialdehyde (MDA) levels in shoots and roots were decreased by 37.6%, 35%, 28.4% and 26.8%. Further, the increases in superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR) and glutathione S-transferase (GST) enzyme activities caused by Cu stress were mitigated in shoots (10.9%-37.1%) and roots (14.6%-35.3%) with SNPs addition. SNPs also positively counteracted the negative effects on shoot K, Ca, P, Mg, Mn, Zn and Fe contents and root K, Ca, Mg and Mn contents from Cu exposure alone, and significantly promoted the nutrients accumulation in plant. Additionally, in comparison with common bulk sulfur particles (BSPs) and sulfate, SNPs showed more positive effects on promoting growth in shoots (6.7% and 19.5%) and roots (10.9% and 15.1%), as well as lowering the shoot Cu content (40.1% and 43.3%) under Cu stress. Thus, SNPs application has potential to be a green and sustainable technology for increasing plant productivity and reducing accumulation of toxic metals in heavy metal polluted soils.

Synthesis, characterization, and evaluation of novel cell-penetrating peptides based on TD-34.

In this study, six N-1, N-2, or N-11 derivatives of TD-34 (a cationic cyclic cell-penetrating peptide [CPP], ACSSKKSKHCG) were designed and synthesized including both linear peptides and cyclic peptides, such as DL-1 (KWSSKKSKHCG), DLCC-1 (cyclopeptide, KWSSKKSKHCG), DL-2 (KWSSKKSKHCG-NH2 ), DLCC-2 (cyclopeptide, KWSSKKSKHCG-NH2 ), DL-3 (RWSSKKSKHCG), and DLCC-3 (cyclopeptide, RWSSKKSKHCG). The cyclic peptides were synthesized by disulfide bound linkages formed by N-2 and N-10 cysteine. In vitro penetration experiment was conducted to investigate the transdermal enhancement ability of these derivatives, using triptolide (TP) as model drug. The results display that at the presence of DLCC-2, the accumulative penetration amount of TP increased 1.71-fold (P < .05) within 12 hours, displaying better transdermal enhancing ability than TD-34. Meanwhile, DL-3 and DLCC-3 slightly decreased the transdermal delivery of TP, and the presence of DL-1 and DLCC-1 shows no obvious effect. In order to clarify the factors on the transdermal ability of peptides, the solubility of TP in phosphate buffer saline (PBS) at the presence of different peptides and the mechanism of transdermal delivery of CPPs was investigated. The result shows that most of these peptides have no significant effect on the solubility of TP except DLCC-3 (the solubility of TP slightly increased). And in order to investigate transdermal absorption route of DLCC-2, polyarginine linked to rhodamine b (Rh b) derivative is used. The result proved that the transdermal route of polyarginine is via hair follicle, which may change the transdermal route of its cargo molecule (TP). Our group previously proved that polyarginine and TD-34 have similar transdermal enhancing mechanism (changing the transdermal route of their cargo molecule); it is reasonably speculated that the transdermal route of DLCC-2 is the same as polyarginine and then changes the transdermal absorption route of TP. Furthermore, such results have laid a solid foundation for further investigation of CPPs and paved a way for both designing and synthesizing of new drug delivery system for therapy molecules.

[Identification of the chemical compositionsof Verbena officinalis L. extract by high performance liquid chromatography-photodiode array-high resolution mass spectrometry].

To investigate the main chemical compositions of Verbena officinals L. extract, a qualitative high performance liquid chromatography-photodiode array-high resolution mass spectrometry (HPLC-PDA-HRMS) method was established. The structures of the compounds detected were identified by analyzing the chromatographic profiles and the corresponding mass spectra obtained by full scan and MSn full scan. Twenty one compounds including iridoid glycosides, flavonoids, triterpenoids, phenylpropanoids and phenolic diterpenoids were identified, and six of them were not reported in other literatures about Verbena officinalis L. extract, such as carnosic acid, carnosol, rosmanol, isorosmanol, rosmarinic acid and acacetin-7-O-rutinoside. This method is simple, rapid, accurate and sensitive. It provides a reliable scientific basis for the identification of the authenticity and quality control of Chinese medicinal materials.

Outcome of Radical Surgical Resection for Craniopharyngioma with Hypothalamic Preservation: A Single-Center Retrospective Study of 1054 Patients.

OBJECTIVE: A retrospective review of the surgical outcome for patients with craniopharyngioma (CP) treated in a single neurosurgical center with surgical resection using visualization to ensure hypothalamic preservation. METHODS: The study included 1054 patients. Before 2003, a pterional cranial approach was preferred for 78% of patients; after 2004, the unifrontal basal interhemispheric approach was performed in 79.1% of patients. RESULTS: Complete tumor resection was achieved in 89.6% of patients; vision improved in 47.1% of patients who had preoperative vision impairment. However, diabetes insipidus worsened in 70.4% of patients and new-onset diabetes insipidus occurred in 29.7% of the remaining patients. Pituitary stalk preservation occurred in 48.9% of cases. There were 89.6% of patients with total tumor removal; 13.3% of patients showed tumor recurrence within an average of 2.8 years. Of 69 follow-up patients with a subtotal or partial resection, 94.2% showed tumor recurrence within an average of 4.3 months. Of the total patients, 82.3% fully recovered. CONCLUSIONS: This study has shown that radical surgical resection of CP using microsurgical excision can be effective with a good patient outcome without more limitations on each individual tumor of distinct features despite the impact of recent endoscopic techniques on CP surgery. The surgical approach depends on a direct and wider visualization of CP located in the midline with preserving hypothalamic structures by identifying some hypothalamic landmark structures. After surgery, most patients can resume their normal activities even after aggressive tumor removal, although patients require postoperative hormonal replacement.

Pharmacokinetics and pharmacodynamics of glycyrrhetinic acid with Paeoniflorin after transdermal administration in dysmenorrhea model mice.

BACKGROUND: Glycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine. HYPOTHESIS/PURPOSE: The aim of this work was to investigate the combinatory analgesic effect of GA and PF after percutaneous administration and to define their pharmacokinetic/pharmacodynamic (PK/PD) characteristics. STUDY DESIGN AND METHODS: GA and PF were produced to transdermal patches based on previous research, and the permeation parameters of GA and PF in the patches were investigated with in vitro experiments. Dysmenorrhea model mice were then produced to compare the analgesic effects of the patches with different proportions of GA-PF. In the in vivo assessment, the number of writhes exhibited by the dysmenorrhea mice was recorded at designated time points, and skin, muscle under skin and plasma samples were collected, for assessments of drug distribution, pharmacokinetics parameters and PK/PD characteristics. RESULTS AND CONCLUSION: In dysmenorrhea mice, GA-PF and meloxicam (the positive control drug) could relieve pain to equal degrees. Specifically, a single dose of the optimized patches (10%GA-10%PF, wt) exerted a steady analgesic effect for 48h in dysmenorrhea mice, but this effect lagged behind the changes in the plasma concentration. Evaluation with the Bliss Independence criterion revealed that the two ingredients displayed a synergistic effect. Then the PK/PD relationship of GA in this compound preparation was defined with this synergistic effect. The preparation might be suitable for topical spasmolysis and anti-inflammatory therapy.

Metabolism and pharmacokinetics of 8-hydroxypiperidinylmethyl-baicalein (BA-j) as a novel selective CDK1 inhibitor in monkey.

Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in the cell proliferation process and a new target in the research and development of anti-cancer drugs. 8-Hydroxypiperidinemethyl-baicalein (BA-j) is a Mannich base derivative of baicalein (BA) isolated from Scutellaria baicalensis, as a novel selective CDK1 inhibitor. 12 metabolites of BA-j in the monkey urine were identified by LC-MS-MS and (1)H NMR. The major metabolic pathways of BA-j, by capturing oxygen free radicals ((.)O2(-)) and releasing peroxides (H2O2), are degraded into active intermediate metabolite dihydroflavonol, then into main metabolite M179 by Shiff reaction, second metabolite M264 by sulfation, trace amount of metabolite M559 by glucuronidation UGT1A9, and without metabolism by CYP3A4. The metabolic process of BA-j by regulating intracellular reactive oxygen species (ROS) was related with BA-j selectively inducing apoptosis in cancer cells. Pharmacokinetics of 10mg/kg oral BA-j in monkey by HPLC-UV was best fitted to a two-compartment open model, with t1/2(ß) of 4.2h, Cmax 25.4µM at 2h, and Vd 12.6L, meaning the drug distributing widely in body fluids with no special selectivity to certain tissues, and being able to permeate through the blood-brain barrier. The protein binding rate of BA-j was 91.8%. BA-j has excellent druggability for oral administration or injection, and it may be developed into a novel anti-cancer drug as a selective CDK1 inhibitor.

Glutamine supplementation for critically ill adults.

BACKGROUND: Glutamine is a non-essential amino acid which is abundant in the healthy human body. There are studies reporting that plasma glutamine levels are reduced in patients with critical illness or following major surgery, suggesting that glutamine may be a conditionally essential amino acid in situations of extreme stress. In the past decade, several clinical trials examining the effects of glutamine supplementation in patients with critical illness or receiving surgery have been done, and the systematic review of this clinical evidence has suggested that glutamine supplementation may reduce infection and mortality rates in patients with critical illness. However, two recent large-scale randomized clinical trials did not find any beneficial effects of glutamine supplementation in patients with critical illness. OBJECTIVES: The objective of this review was to:1. assess the effects of glutamine supplementation in critically ill adults and in adults after major surgery on infection rate, mortality and other clinically relevant outcomes;2. investigate potential heterogeneity across different patient groups and different routes for providing nutrition. SEARCH METHODS: We searched the Cochrane Anaesthesia Review Group (CARG) Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 5); MEDLINE (1950 to May 2013); EMBASE (1980 to May 2013) and Web of Science (1945 to May 2013). SELECTION CRITERIA: We included controlled clinical trials with random or quasi-random allocation that examined glutamine supplementation versus no supplementation or placebo in adults with a critical illness or undergoing elective major surgery. We excluded cross-over trials. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the relevant information from each included study using a standardized data extraction form. For infectious complications and mortality and morbidity outcomes we used risk ratio (RR) as the summary measure with the 95% confidence interval (CI). We calculated, where appropriate, the number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH). We presented continuous data as the difference between means (MD) with the 95% CI. MAIN RESULTS: Our search identified 1999 titles, of which 53 trials (57 articles) fulfilled our inclusion criteria. The 53 included studies enrolled a total of 4671 participants with critical illness or undergoing elective major surgery. We analysed seven domains of potential risk of bias. In 10 studies the risk of bias was evaluated as low in all of the domains. Thirty-three trials (2303 patients) provided data on nosocomial infectious complications; pooling of these data suggested that glutamine supplementation reduced the infectious complications rate in adults with critical illness or undergoing elective major surgery (RR 0.79, 95% CI 0.71 to 0.87, P ＜ 0.00001, I² = 8%, moderate quality evidence). Thirty-six studies reported short-term (hospital or less than one month) mortality. The combined rate of mortality from these studies was not statistically different between the groups receiving glutamine supplement and those receiving no supplement (RR 0.89, 95% CI 0.78 to 1.02, P = 0.10, I² = 22%, low quality evidence). Eleven studies reported long-term (more than six months) mortality; meta-analysis of these studies (2277 participants) yielded a RR of 1.00 (95% CI 0.89 to 1.12, P = 0.94, I² = 30%, moderate quality evidence). Subgroup analysis of infectious complications and mortality outcomes did not find any statistically significant differences between the predefined groups. Hospital length of stay was reported in 36 studies. We found that the length of hospital stay was shorter in the intervention group than in the control group (MD -3.46 days, 95% CI -4.61 to -2.32, P < 0.0001, I² = 63%, low quality evidence). Slightly prolonged intensive care unit (ICU) stay was found in the glutamine supplemented group from 22 studies (2285 participants) (MD 0.18 days, 95% CI 0.07 to 0.29, P = 0.002, I² = 11%, moderate quality evidence). Days on mechanical ventilation (14 studies, 1297 participants) was found to be slightly shorter in the intervention group than in the control group (MD - 0.69 days, 95% CI -1.37 to -0.02, P = 0.04, I² = 18%, moderate quality evidence). There was no clear evidence of a difference between the groups for side effects and quality of life, however results were imprecise for serious adverse events and few studies reported on quality of life. Sensitivity analysis including only low risk of bias studies found that glutamine supplementation had beneficial effects in reducing the length of hospital stay (MD -2.9 days, 95% CI -5.3 to -0.5, P = 0.02, I² = 58%, eight studies) while there was no statistically significant difference between the groups for all of the other outcomes. AUTHORS' CONCLUSIONS: This review found moderate evidence that glutamine supplementation reduced the infection rate and days on mechanical ventilation, and low quality evidence that glutamine supplementation reduced length of hospital stay in critically ill or surgical patients. It seems to have little or no effect on the risk of mortality and length of ICU stay, however. The effects on the risk of serious side effects were imprecise. The strength of evidence in this review was impaired by a high risk of overall bias, suspected publication bias, and moderate to substantial heterogeneity within the included studies.

[Clinical study on sodium ferulate for intracerebral hemorrhage in early stage].

OBJECTIVE: To evaluate the clinical application value of sodium ferulate for intracerebral hemorrhage in early stage. METHOD: Sixty patients with cerebral hemorrhage in basal ganglia onset within 24 h were randomly divided into two groups. The two groups showed no evident differences in age, hematoma volume and edema volume, computerized tomography number, and Chinese Stroke Scale. Both groups were given basic treatment with dehydrating, cytidine diphosphocholine, controlling blood pressure, blood sugar and complicating diseases, while the observation group added the treatment of sodium ferulate intravenous drip after 24 h. The hematoma volume, edema volume, and computerized tomographynumber were examined in the 1st day and 14th day, Chinese Stroke Scale in the 1st day, 14th day and 28th day, and the level of serum endothelin in the 1, 3, 5, 7, 14th day. RESULT: After treatment, edema volume and computerized tomography number in the observation group were lower than those in the control group (P < 0.01, P < 0.05). Patients' recovery of neural function were markedly improved in the observation group better than that in the control group (P < 0.05), and also the therapeutic effectiveness (P < 0.05). The serum endothelin level of the 60 patients showed higher significantly than the healthy group in 24 h after hemorrhage (P < 0.01). The control group kept higher in 14 days (P < 0.05), while the observation group showed declined significantly in the 3rd day and close to the healthy group, and lower than the healthy group in the 14th day (P < 0.05). CONCLUSION: With the basic medical therapy, applying sodium ferulate can effectually improve the resolution of the haematoma, reduce the peripheral edema, and enhance the recovery of neural function for the patients with intracerebral hemorrhage in early stag. The therapeutic effectiveness of adding sodium ferulate in patients with intracerebral hemorrhage in early stage is better than that of the basic medical therapy in most of the fields as the above. No evident effect on secondary hemorrhage, or harmful impact on heart, liver and kidney function was found.