A Chromatographic Approach for High-Precision Eu Isotope Analysis.

Eu isotopes are promising tracers across various scientific domains such as planetary, earth, and marine science, yet their high-precision analysis has been challenging due to the similar geochemical properties of rare earth elements (REEs). In this study, a novel two-column chromatographic approach was developed utilizing AG50W-X12 and TODGA resins to separate Eu effectively from matrix and interfering elements like Ba, Nd, Sm, and Gd, while ensuring high Eu yields (99.4 ± 0.4%, n = 19) and low blanks (<20 pg). The robustness of this method is evidenced by various rock types and different Eu loading masses. The efficient purification of Eu facilitated the establishment of a high-precision calibration technique with standard-sample bracketing (SSB) and internal normalization (Nd). When a Nu Plasma 1700 multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) instrument was employed, repeated purification and analysis of various Geological Reference Materials (GRMs) confirmed that the long-term external precision of δ153/151Eu is better than 0.04‰ (2 standard deviation (2SD)), which represents a 2-5-fold increase in precision compared to previously reported methods. Additionally, the high-precision Eu isotopic compositions of five GRMs, including basalts, andesite, syenite, and marine sediment, were measured. The high-precision Eu isotope techniques presented herein open up new avenues for Eu isotope geochemistry.

Inhibition of hepatocellular carcinoma cell proliferation through regulation of the Cell Cycle, AGE-RAGE, and Leptin signaling pathways by a compound formulation comprised of andrographolide, wogonin, and oroxylin A derived from Andrographis Paniculata(Burm.f.) Nees.

ETHNOPHARMACOLOGICAL RELEVANCE: In 2020, liver cancer contributed to approximately 0.9 million new cases and 0.83 million deaths, making it the third leading cause of mortality worldwide. Andrographis paniculata (Burm.f.) Nees(APN), a traditional Chinese or ethnic medicine extensively utilized in Asia, has been historically employed for treating hepatitis and liver cancer. However, the precise molecular mechanism responsible for its therapeutic efficacy remains unclear. AIM OF THE STUDY: To identify and replace the active components of APN on liver cancer, which is investigate the potential of a Multi-Component Chinese Medicine derived from Andrographis paniculata (Burm.f.) Nees(APN-MCCN) for the treatment of liver cancer. MATERIALS AND METHODS: Firstly, the TCMSP database and two liver cancer disease databases were utilized to optimize the chemical constituents of APN and the disease-related targets of liver cancer. The network was constructed using Cytoscape to visualize the relationships between them. Subsequently, the optimal combination of components in APN-MCCN for the treatment of liver cancer was determined using the contribution index method. HPLC analysis was performed to measure the content of each component. Pathway enrichment and gene annotation were conducted using the ClueGo plugin. In vivo efficacy was evaluated by transplanting S180 and H22 tumor-bearing mouse models. In vitro efficacy was determined through MTT assay, morphological observations, flow cytometry analysis, and scratch tests. Western blotting was used to validate the protein expression. The transfection techniques were employed to knockdown the expressions of key protein in different pathway. RESULTS: We obtained 24 effective compounds, with andrographolide contributing 20.78%, wogonin contributing 41.85%, and oroxylin A contributing 30.26% to the overall composition. Based on the predicted enrichment degree and correlation with liver cancer, we identified a total of 27 pathways, among which the Leptin signaling pathway, AGE-RAGE signaling pathway, and Cell Cycle signaling pathway were selected for further investigation. The content of andrographolide, oroxylin A, and wogonin in APN was found to be 0.104%, 0.0024%, and 0.0052%, respectively. In vivo experiments demonstrated that APN-MCCM significantly reduced tumor weight in S180 tumor-bearing mice and prolonged the survival time of H22 liver cancer-bearing mice. APN-MCCM exhibited inhibitory effects on the proliferation, apoptosis, and migration of liver cancer cells while arresting them in the G2/M phase. Furthermore, APN-MCCM down-regulated the protein expression of NCOA1, PTPN1, and GSK3B in the Leptin signaling pathway, NOS2 and NOS3 in the AGE-RAGE signaling pathway, CCNA2, CDK1, CDK2, and CDK7 in the Cell Cycle signaling pathway. Additionally, it upregulated the protein phosphorylation of p-P38 and p-JUN in the AGE-RAGE signaling pathway. Knockout experiments revealed that the inhibitory effect of APN-MCCM on liver cancer cell migration was prevented when the MAPK or NCOA1 genes were knocked out. Similarly, knocking out the CDK7 gene blocked the G2/M phase arrest induced by APN-MCCM in liver cancer cells. CONCLUSIONS: APN-MCCM, consisting of andrographolide, wogonin, and oroxylin A, exhibits inhibitory effects on the cell proliferation of liver cancer cells by targeting the cell cycle pathway. Additionally, it suppresses the migration of liver cancer cells through the AGE-RAGE and Leptin signaling pathways.

A Novel Classification and Scoring Method Based on Immune-Related Transcription Factor Regulation Patterns in Gastric Cancer.

Background: Transcription factors (TFs) play a crucial role in tumorigenesis and anti-tumor immunity. However, the potential role of large-scale transcription factor regulation patterns in the progression in gastric cancer (GC) is unknown. Methods: We comprehensively assessed the relevance of immune-related TF (IRTF) regulation patterns in anti-tumor immunity and immunotherapy in 1,136 gastric cancer (GC) patients, and evaluated the IRTF score based on IRTF regulation patterns using random forests. Results: Two distinct IRTF regulation patterns were identified, which demonstrating the distinct characteristics in clinical phenotypes, tumor immune microenvironment (TIME), immunogenicity and prognosis in GC. Subsequently, the IRTF score was established to quantify the IRTF regulation pattern for each GC patient. Analysis of large conventional therapy cohorts showed low IRTF score was associated with a better prognosis. In addition, analysis of multiple immunotherapy cohorts showed low IRTF score was also linked to enhanced response to immunotherapy. Conclusion: TF regulation patterns were found to play an important role in the complex immune regulatory relationships in GC. Evaluation of the IRTF regulation patterns in patients will enhance our understanding of immune specificities, and thus, provide effective strategies for personalized therapy.

Computational analysis for identification of early diagnostic biomarkers and prognostic biomarkers of liver cancer based on GEO and TCGA databases and studies on pathways and biological functions affecting the survival time of liver cancer.

BACKGROUND: Liver cancer is the sixth most commonly diagnosed cancer and the fourth most common cause of cancer death. The purpose of this work is to find new diagnostic biomarkers or prognostic biomarkers and explore the biological functions related to the prognosis of liver cancer. METHODS: GSE25097 datasets were firstly obtained and compared with TCGA LICA datasets and an analysis of the overlapping differentially expressed genes (DEGs) was conducted. Cytoscape was used to screen out the Hub Genes among the DEGs. ROC curve analysis was used to screen the Hub Genes to determine the genes that could be used as diagnostic biomarkers. Kaplan-Meier analysis and Cox proportional hazards model screened genes associated with prognosis biomarkers, and further Gene Set Enrichment Analysis was performed on the prognosis genes to explore the mechanism affecting the survival and prognosis of liver cancer patients. RESULTS: 790 DEGs and 2162 DEGs were obtained respectively from the GSE25097 and TCGA LIHC data sets, and 102 Common DEGs were identified by overlapping the two DEGs. Further screening identified 22 Hub Genes from 102 Common DEGs. ROC and survival curves were used to analyze these 22 Hub Genes and it was found that there were 16 genes with a value of AUC > 90%. Among these, the expression levels of ESR1,SPP1 and FOSB genes were closely related to the survival time of liver cancer patients. Three common pathways of ESR1, FOBS and SPP1 genes were identified along with seven common pathways of ESR1 and SPP1 genes and four common pathways of ESR1 and FOSB genes. CONCLUSIONS: SPP1, AURKA, NUSAP1, TOP2A, UBE2C, AFP, GMNN, PTTG1, RRM2, SPARCL1, CXCL12, FOS, DCN, SOCS3, FOSB and PCK1 can be used as diagnostic biomarkers for liver cancer, among which FOBS and SPP1 genes can also be used as prognostic biomarkers. Activation of the cell cycle-related pathway, pancreas beta cells pathway, and the estrogen signaling pathway, while on the other hand inhibition of the hallmark heme metabolism pathway, hallmark coagulation pathway, and the fat metabolism pathway may promote prognosis in liver cancer patients.

Copper(II)-catalysed direct C3-H esterification of indoles assisted by an N,N-bidentate auxiliary moiety.

The regioselective direct C3-esterification of indoles with OXA is developed in an efficient reaction with carboxylic acids using the catalyst CuBr2 and oxidants Ag2CO3 and K2S2O8. The simple experimental procedure is proved to be broadly applicable to a range of substrates, including aromatic and aliphatic acids, and the corresponding products were obtained in good yields up to 87%. At the same time, it provides a valuable approach to produce C3-benzyl derivatives of indoles through reaction with benzyl carboxylic acid under the same reaction conditions.

Copper(II)-Catalyzed Direct C-H (Hetero)arylation at the C3 Position of Indoles Assisted by a Removable N,N-Bidentate Auxiliary Moiety.

The regioselective arylation of inert C3-H bonds in indoles reacting with arylboronates via effective copper-mediated catalysis with the aid of a facile and removable 2-pyridinylisopropyl (PIP) group without ligand participation is reported. This newly established method features high compatibility with diverse functional groups between coupling partners, including both indole substrates and arylboron reagents, consequentially leading to operational simplicity and providing access to generate the desired arylated products in good to excellent yields of up to 97%. Synthetically, the PIP-derived amide moiety could subsequently be readily removed under mild reaction conditions to produce useful indole carboxylic acids for further transformation.

Pain management after ambulatory surgery: a prospective, multicenter, randomized, double-blinded parallel controlled trial comparing nalbuphine and tramadol.

BACKGROUND: Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. METHODS: This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. RESULTS: The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. CONCLUSIONS: Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. TRIAL REGISTRATION: The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.

The nickel-catalyzed C3-acylation of 2H-indazoles with aldehydes.

A direct coupling of 2H-indazoles' C3 position and acyl groups has been achieved to produce 3-acyl-2H-indazoles. The Ni(ii)-catalyzed acylation might proceed through a radical pathway for the reaction of 2H-indazoles with either aryl or alkyl aldehydes in the presence of the free radical initiator TBHP and additive PivOH. This method provided a superior approach to fulfil the direct C3-acylation of 2H-indazoles with yields up to 91%. And various substituted 2H-indazoles were well tolerated with this method, enriching the diversity of 2H-indazole derivatives. In comparison with previously reported approaches for the C3-acylation of 2H-indazoles, the developed reaction represents a more convenient and economical method directly using aldehydes as the acylation agents.

Direct Acyloxylation of C(sp2)-H and C(sp2)-X (X = Cl, Br) Bonds in Aromatic Amides Using Copper Bromide and 2-(4,5-Dihydro-oxazol-2-yl)-phenylamine.

Here we reported a method for Cu2+-catalyzed ortho-acyloxylation of either the C(sp2)-H or C(sp2)-X (X = Cl, Br) bond of aromatic amides with carboxylic acid, especially olefine acids, to obtain corresponding products in good yields up to 91%. The catalyst CuBr2 is cheap and stable to conserve in comparison with other metals, like Rh, Pd, Ru, and Cu+. This simple procedure is applicable for wide substrate scope and various functional groups to produce carboxylic esters without any additives or ligands.

Assessment of three methods for removing massive air in a cardiopulmonary bypass circuit: simulation-based multi-discipline training in West China Hospital.

BACKGROUND AND OBJECTIVE: A multi-discipline cardiac and cardiopulmonary bypass (CPB) team simulation scenario was established to compare three different de-airing approaches dealing with massive air embolism in CPB, so as to formulate a standardized procedure to handle this adverse acute event more proficiently and ensure clinical safety. METHOD: A simulation-based clinical CPB massive air embolism scenario was developed by a cardiac and CPB team. Study Objects: Five licensed perfusionists and five CPB trainees were matched randomly into five pairs. Each pair would simulate the three different de-airing approaches separately as followed: (1) Conventional Method: arterial line filter (ALF) de-airing purge line and oxygenator self-recirculation bypass were used to de-air; (2) Arterial-Venous Loop (A-V Loop) Method: surgeons reconnected the arterial and venous lines to de-air by restoring the original priming A-V loop configuration; (3) Isolation of the ALF Method: this ensures de-bubbling of the CPB circuit, but bypasses the ALF function. Assessment Criteria: (1) Times to recovery (duration of the circulation suspension); (2) Subjective evaluation of skill and non-skill performances. RESULTS: As to times to recovery, the Conventional Method group took 290.6 s ± 36.2, the A-V Loop Method group took 196.8 s ± 52.0 and the Isolation of ALF group took 99.4 s ± 15.1. The statistical difference is significant among the three groups (p<0.01). The subjective evaluation of training performance indicates that this simulation-based training is effective in assessing both skill and non-skill abilities. CONCLUSION: CPB simulation-based training was effective in comparing de-airing strategies and can instruct perfusion practices how to optimize techniques. For well-trained, multi-discipline cardiac teams, the A-V Loop Method is highly efficient and reliable in managing CPB massive air embolism. For cardiac teams that do not have this sophisticated training, the Isolation of ALF Method should be their alternative option.

Developing pyridazine-3-carboxamides to be CB2 agonists: The design, synthesis, structure-activity relationships and docking studies.

Herein, we described the design and synthesis of a series of pyridazine-3-carboxamides to be CB2-selective agonists via a combination of scaffold hopping and bioisosterism strategies. The compounds were subjected to assessment of their potential activities through calcium mobilization assays. Among the tested derivatives, more than half of these compounds exhibited moderate to potent CB2 agonist activity. Six compounds showed EC50 values below 35 nM, and several derivatives also exhibited significantly enhanced potency and high selectivity at the CB2 receptor over the CB1 receptor. Specifically, compound 26 showed the highest CB2 agonist activity (EC50 = 3.665 ± 0.553 nM) and remarkable selectivity (Selectivity Index > 2729) against CB1. In addition, logPs of some representative compounds were measured to display significantly decreased values in comparison with GW842166X. Furthermore, docking simulations were conducted to explain the interaction mode of this series.

Oridonin induces apoptosis through the mitochondrial pathway in human gastric cancer SGC-7901 cells.

Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G2/M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridonin-mediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC50) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Western blot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells.

Alpha7 nicotinic acetylcholine receptor activation attenuated intestine-derived acute lung injury.

BACKGROUND: Intestinal ischemia-reperfusion (IIR) could lead to acute lung injury, associated with severe alveolar epithelial cells inflammatory and oxidative injury. Alpha7 nicotinic acetylcholine receptor (α7nAChR) is an essential component of the cholinergic anti-inflammatory pathway. The aim of this study was to investigate the important role of α7nAChR on the lung subjected to IIR. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups (n = 8 in each): sham group (group S), model group (group M), α7nAChR agonist PNU-282987-treated group (group PNU), and specific α7nAChR antagonist methyllycaconitine-treated group (group MLA). Intestinal IR damage was induced by clamping the superior mesenteric artery for 75 min, followed by a 120-min reperfusion. All rats were killed at 2 h after release of the clamps. The histologic examination of lungs was made, and lung water content was detected. Expression levels of malondialdehyde, tumor necrosis factor alpha, interleukin-6, and superoxide dismutase activity of the lungs were detected. Additionally, expression level of toll-like receptor (TLR)4 and nuclear factor-kappaB (NF-κB p65) in the nucleus of lung tissue and apoptosis-related protein (Bax, Bcl-2, and cleaved-caspase3) were detected using Western blot. RESULTS: Lungs were damaged after intestine IR, manifested by higher lung water content, histologic score, concentrations of interleukin-6, tumor necrosis factor alpha, and malondialdehyde of group M than those of group S, accompanied with decreased superoxide dismutase activity (P < 0.05). PNU treatment could significantly improve the pulmonary function of rats subjected to IIR. These effects of activation of α7nAChR were associated with suppression of TLR4/NF-κB pathway and subsequent reduction of apoptosis-related protein. However, MLA treatment aggravated lung injury. CONCLUSIONS: α7nAChR plays a role in acute lung injury induced by IIR via attenuating lung oxidative stress and inflammation through suppression of TLR4/NF-κB pathway, resulting in reduction of apoptosis in the lung.

[Survey on Echinococcosis in Maqing County of Qinghai Province].

OBJECTIVE: To understand the status of echinococcosis in Maqing County of Qinghai Province in order to facilitate echinococcosis control in this region. METHODS: Ultrasonic scanning and indirect hemagglutination assay were used to detect echinococcosis infection in residents >1 year old, according to the People's Republic of China Health Industry Standard--Diagnostic Criteria for Hydatid Disease (WS257-2006). Meanwhile, ELISA was used o detect the Echinococcus antigen in dog's feces collected in Youyun, Dangluo and Xiadawu townships. RESULTS: Ultrasonic scanning showed that the prevalence of hydatid disease in the residents was 7.4% (116/1 561), cystic hydatid disease 5.3% (82/1 561), alveolar hydatid disease 2.2% (34/1 561). The serum positive rate in human population was 23.8%(307/1 288). Of the 82 cases of cystic hydatid disease, 23 cases (28.1%) had the hydatid cyst with a diameter of >10 cm. The prevalence in males and females in the county was 5.3% (40/753) and 9.4% (76/808), respectively (P<0.05). Among populations with different occupations, the highest prevalence of hydatid disease fell into houseworkers (11/61, 18.0%), monks (5/41, 12.2%) and herdsmen (84/758, 11.1%). Among the age groups, the groups of >60 years (24/132, 18.2%) and 30-40 years (31/302, 10.3%) had higher prevalence of hydatid disease. The three townships with the higher prevalence were Youyun (29/247, 11.7%), Changmahe (6/63, 9.5%) and Dangluo (54/645, 8.4%). Of the 199 samples of dog's feces, 54 were positive for Echinococcus antigens (27.1%), with a positive rate of 40.4% (23/57) in Youyun towship, being significantly higher than in the other two (P<0.05). CONCLUSION: Maqin county is a co-endemic area of cystic echinococcosis and alveolar echinococcosis. The prevalence is higher in females and those over 60 years-old.

In Vivo Evaluation of the Ameliorating Effects of Small-Volume Resuscitation with Four Different Fluids on Endotoxemia-Induced Kidney Injury.

Acute kidney injury associated with renal hypoperfusion is a frequent and severe complication during sepsis. Fluid resuscitation is the main therapy. However, heart failure is usually lethal for those patients receiving large volumes of fluids. We compared the effects of small-volume resuscitation using four different treatment regimens, involving saline, hypertonic saline (HTS), hydroxyethyl starch (HES), or hypertonic saline hydroxyethyl starch (HSH), on the kidneys of rats treated with lipopolysaccharide (LPS) to induce endotoxemia. LPS injection caused reduced and progressively deteriorated systemic (arterial blood pressure) and renal hemodynamics (renal blood flow and renal vascular resistance index) over time. This deterioration was accompanied by marked renal functional and pathological injury, as well as an oxidative and inflammatory response, manifesting as increased levels of tumor necrosis factor-α, nitric oxide, and malondialdehyde and decreased activity of superoxide dismutase. Small-volume perfusion with saline failed to improve renal and systemic circulation. However, small-volume perfusion with HES and HSH greatly improved the above parameters, while HTS only transiently improved systemic and renal hemodynamics with obvious renal injury. Therefore, single small-volume resuscitation with HES and HSH could be valid therapeutic approaches to ameliorate kidney injury induced by endotoxemia, while HTS transiently delays injury and saline shows no protective effects.

Screening antitumor bioactive fraction from Sauromatum giganteum (Engl.) Cusimano & Hett and sensitive cell lines with the serum pharmacology method and identification by UPLC-TOF-MS.

Sauromatum giganteum (Engl.) Cusimano & Hett Tuber are used in Chinese folklore medicine for treatment of neoplasms. However, the claim has not been scientifically validated. The aim of the study is to screen the antitumor bioactive fraction of Sauromatum giganteum (Engl.) Cusimano & Hett Tuber and sensitive tumor cell lines using a cytotoxicity assay in vitro and tumor transplantation method in vivo, to support its use in folk medicine. The petroleum ether fraction, chloroform fraction, ethyl acetate fraction, n-butanol fraction and water fraction were successively extracted by turn by the maceration under reflux assay. Screening of antitumor bioactive fraction and sensitive cell lines were measured by MTT assay and the serum pharmacology method, and in vivo the antitumor activities of the active fraction was evaluated by using S180 or H22 tumor-bearing mice model and Kunming mice. The active constituents of ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett were characterized by UPLC-TOF-MS. Compared with control groups, mice serum containing ethyl acetate fraction had a inhibition effect on SMMC-7721 cell, SGC-7901 cell, MCF-7 cell, HeLa cell, A549 cell, HT-29, and MDA-MB-231, respectively, but mice serum containing other four fractions had no different with that of control group. The inhibition capabilities of mice serum containing ethyl acetate fraction on the seven cell lines in descending order is SGC-7901 > SMMC-7721 > MCF-7 > HT-29 > A549 > HeLa > MDA-MB-231. In vivo the inhibition rate of 106, 318, 954 mg/kg·d ethyl acetate fraction dry extract to sarcoma S180 is 15.22%, 26.15% and 40.24%, respectively, and life prolonging rate to hepatoma H22 is 33.61%, 40.16% and 55.74%. A total of 14 compounds were identified in the ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett. The results of the experimental studies proved the antitumor activity of Sauromatum giganteum (Engl.) Cusimano & Hett and supported the traditional use of this plant. These data indicate the potential for the use of ethyl acetate fraction of Sauromatum giganteum (Engl.) Cusimano & Hett Tuber in tumor therapy, anti-tumor activity on cancer cell line in descending order is SGC-7901 > SMMC-7721 > MCF-7 > HT-29 > A549 > HeLa > MDA-MB-231.

HDAC4 degradation mediates HDAC inhibition-induced protective effects against hypoxia/reoxygenation injury.

Histone deacetylases (HDACs) play a crucial role in the regulation of gene expression through remodeling of chromatin structures. However, the molecular mechanisms involved in this event remain unknown. In this study, we sought to examine whether HDAC inhibition-mediated protective effects involved HDAC4 sumoylation, degradation, and the proteasome pathway. Isolated neonatal mouse ventricular myocytes (NMVM) and H9c2 cardiomyoblasts were subjected to 48 h of hypoxia (H) (1% O2 ) and 2 h of reoxygenation (R). Treatment of cardiomyocytes with trichostatin A (TSA) attenuated H/R-elicited injury, as indicated by a reduction of lactate dehydrogenase (LDH) leakage, an increase in cell viability, and decrease in apoptotic positive cardiomyocytes. MG132, a potent proteasome pathway inhibitor, abrogated TSA-induced protective effects, which was associated with the accumulation of ubiquitinated HDAC4. NMVM transduced with adenoviral HDAC4 led to an exaggeration of H/R-induced injury. TSA treatment resulted in a decrease in HDAC4 in cardiomyocytes infected with adenoviral HDAC4, and HDAC4-induced injury was attenuated by TSA. HDAC inhibition resulted in a significant reduction in reactive oxygen species (ROS) in cardiomyoblasts exposed to H/R, which was attenuated by blockade of the proteasome pathway. Cardiomyoblasts carrying wild type and sumoylation mutation (K559R) were established to examine effects of HDAC4 sumoylation and ubiquitination on H/R injury. Disruption of HDAC4 sumoylation brought about HDAC4 accumulation and impairment of HDAC4 ubiquitination in association with enhanced susceptibility of cardiomyoblasts to H/R. Taken together, these results demonstrated that HDAC inhibition stimulates proteasome dependent degradation of HDAC4, which is associated with HDAC4 sumoylation to induce these protective effects.

Ulinastatin prevents acute lung injury led by liver transplantation.

BACKGROUND: Little is known regarding the effect of ulinastatin (UTI) on acute lung injury (ALI) induced by orthotopic liver transplantation. This study aims to investigate the protective effect of UTI on ALI induced by orthotopic autologous liver transplantation (OALT) in a rat model and to explore the potential underlying mechanism. MATERIALS AND METHODS: Rats were randomly allocated into the following four groups (n = 8 each): (i) sham control group (group sham); (ii) model group (underwent OALT) (group model); (iii) low-dose UTI-treated group (group u1), with UTI (50 U/g) administered intravenously both before the portal vein was occluded and after liver reperfusion started; and (iv) high-dose UTI-treated group (group uh), with UTI (100 U/g) given in the same way as group ul. The lung pathologic parameters, lung water content, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, malondialdehyde (MDA), superoxide dismutase (SOD) activity, RanBP-type and C3HC4-type zinc finger-containing protein 1 (RBCK1), and peroxiredoxin-2 (Prx-2) were assessed 8 h after OALT was performed. RESULTS: According to histology, there was severe damage in the lung of group model accompanied by increases in the TNF-α, IL-1ß, IL-6, and MDA levels and decreases in SOD activity and the expression of RBCK1 and Prx-2. UTI treatment significantly reduced the pathologic scores, lung water content, and TNF-α, IL-1ß, IL-6, and MDA levels while restoring the SOD activity and expression of RBCK1 and Prx-2. Furthermore, compared with group u1, treatment with a high dose of UTI resulted in a better protective effect on the lung when assessed by the TNF-α, IL-1ß, IL-6, and MDA levels and SOD activity. CONCLUSIONS: UTI dose-dependently attenuates ALI that is induced by OALT in this rat model, which is mainly due to the suppression of the inflammatory response and oxidant stress, which may, in turn, be mediated by the upregulation of RBCK1 and Prx-2 expression.

Role of Wnt/ß-catenin signaling pathway in the mechanism of calcification of aortic valve.

Aortic valve calcification is a common disease in the elderly, but its cellular and molecular mechanisms are not clear. In order to verify the hypothesis that Wnt/ß-catenin signaling pathway is involved in the process of calcification of aortic valve, porcine aortic valve interstitial cells (VICs) were isolated, cultured and stimulated with oxidized low density lipoprotein (ox-LDL) for 48 h to induce the differentiation of VICs into osteoblast-like cells. The key proteins and genes of Wnt/ß-catenin signaling pathway, such as glycogen synthase kinase 3ß (GSK-3ß) and ß-catenin, were detected by using Western blotting and real-time polymerase chain reaction (PCR). The results showed that the VICs managed to differentiate into osteoblast-like cells after the stimulation with ox-LDL and the levels of proteins and genes of GSK-3ß and ß-catenin were increased significantly in VICs after stimulation for 48 h (P<0.05). It is suggested that Wnt/ß-catenin signaling pathway may play a key role in the differentiation of VICs into osteoblast-like cells and make great contribution to aortic valve calcification.

Ethanol but not aqueous extracts of tubers of Sauromatum Giganteum(Engl.) Cusimano and Hett inhibit cancer cell proliferation.

BACKGROUND: Both alcohol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett, the dried root tuber of which is named Baifuzi in Chinese, have been used for folklore treatment of cancer in Northeast of China. However, little is known about which is most suitable to the cancer therapy. MATERIALS AND METHODS: Serum pharmacology and MTT assays were adopted to detect the effects of ethanol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett , prepared by heat reflux methods, on proliferation of different cancer cells. RESULTS: Cancer cells treated with medium supplemented with 10%, 20%, 40% serum(v/v) containing ethanol extract had a decline in viability, with inhibition rates of 7.69%, 21.8%, 41.9% in MCF-7 cells, 42.8%, 48.1%, 51.8% in SGC-7901 cells, 44.1%, 49.2%, 53.7% in SMMC-7721 cells, 6.8%, 15.2%, 39.8% in HepG2 cells, 7.57%, 16.3%, 36.2% in HeLa cells, 6.24%, 12.5%, 27.4% in A549 cells, and 7.20%, 17.5%, 31.3% in MDA-MB-231 cells, respectively. Viability in the aqueous extract groups was no different with that of controls. CONCLUSIONS: An ethanol extract of Sauromatum giganteum(Engl.) Cusimano and Hett inhibited the proliferation of SMMC-7721, SGC-7901 and MCF-7 cells, which supports the use of alcoholic but not aqueous extracts for control of sensive cancers, which might include hepatocarcinoma, gastric cancer and breast cancer.