An optimal medicinal and edible Chinese herbal formula attenuates particulate matter-induced lung injury through its anti-oxidative, anti-inflammatory and anti-apoptosis activities / 中草药·英文版

OBJECTIVE@#Identifying novel strategies to prevent particulate matter (PM)-induced lung injury is crucial for the reduction of the morbidity of chronic respiratory diseases. The combined intervention represented by herbal formulae for simultaneously targeting multiple pathological processes can provide a more beneficial effect than the single intervention. The aim of this paper is therefore to design a safe and effective medicinal and edible Chinese herbs (MECHs) formula against PM-induced lung injury.@*METHODS@#PM-induced oxidative stress, inflammatory response and apoptosis A549 cell model were used to screen anti-oxidant, anti-inflammatory and anti-apoptotic MECHs, respectively. A network pharmacology method was utilized to rationally design a novel herbal formula. Ultra performance liquid chromatography-mass spectrometer was utilized to assess the quality control of MECHs formula. The excretion of magnetic iron oxide nanospheres of the MECHs formula was estimated in zebrafish. The MECH formula against PM-induced lung injury was investigated with mice experiments.@*RESULTS@#Five selected herbs were rationally designed to form a new MECH formula, including Citri Exocarpium Rubrum (Juhong), Lablab Semen Album (Baibiandou), Atractylodis Macrocephalae Rhizoma (Baizhu), Mori Folium (Sangye) and Polygonati Odorati Rhizoma (Yuzhu). The formula effectively promoted the magnetic iron oxide nanospheres excretion in zebrafish. The mid/high dose formula significantly prevented PM-induced lung damage in mice by enhancing the activity of SOD and GSH-Px, reducing the MDA and ROS level and attenuating the upregulation of pro-inflammatory cytokine (IL-6, IL-8, IL-1β and TNF-α), down regulating the protein expression of NF-κB, STAT3 and Caspase-3.@*CONCLUSION@#Our findings suggest that the effective MECHs formula will become a novel strategy for preventing PM-induced lung injury and provide a paradigm for the development of functional foods using MECHs.

Molecular Mechanism of Qinghuangsan Against Acute Myeloid Leukemia Based on Network Pharmacology and In Vitro Experiments / 中国实验方剂学杂志

ObjectiveTo predict the therapeutic target genes and related signaling pathways of Qinghuangsan （QHP） in the treatment of acute myeloid leukemia （AML） by network pharmacology，molecular docking，and further clarify its mechanisms through in vitro cell experiment. MethodThe active components and targets of QHP were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP），traditional Chinese medicine integrated database （TCMID），TargetNet and SwissTargetPrediction databases，and AML-related target genes were obtained by GeneCards and online mendelian inheritance in man （OMIM） databases. After screening the common targets of QHP and AML，the protein-protein interaction （PPI） network of the common targets was constructed with STRING，followed by gene ontology （GO） term and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analysis based on RStudio software and clusterProfiler，Bioconductor packages. At the same time，Cytoscape software is used to construct the network of "disease-component-target" and "compound-target-pathway". Select the active ingredients of QHP for molecular docking with the top 8 targets in the "compound-target-pathway" network. In vitro cell experiment and Western blot were used to further verify the anti-AML effect of QHP. ResultThe prediction results show that there are 11 main active components of QHP，and 22 common targets of QHP and AML are collected. KEGG pathway analysis results show that phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and mitogen-activated protein kinase （MAPK） signaling pathways may play a key role in the treatment of AML disease by QHP. "Compound-target-pathway" network analysis showed that the top 8 targets include Akt1，phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA），mitogen-activated protein kinase kinase 1 （MAP2K1），TP53，serine/threonine kinase （RAF1），B cell lymphoma（Bcl）-2，cysteine aspartic acid specific protease（Caspase）-9 and JUN. Molecular docking results showed that 3-indolyl-β-D-glucopyranoside was optimally docked with MAP2K1，isovitexin docked with PIK3CA，and indirubin docked with Bcl-2. Cell experiments show that 3-indolyl-β-D-glucopyranoside，isovitexin and indirubin can effectively inhibit the proliferation of AML cells，regulate the MAPK/PI3K signaling pathway，and inhibit the expression of Bcl-2 protein. ConclusionQHP can treat AML through "multi-component，multi-target，multi-pathway" synergistic treatment，and its mechanism of pharmacology may be related to the regulation of MAPK signaling pathway and PI3K/Akt signaling pathway.

Clinical effect of Fumai Zhuyu Decoction in the adjuvant treatment of deep vein thrombosis after orthopedic surgery / 国际中医中药杂志

Objective:To evaluate the curative effect of Fumai Zhuyu Decoction on deep vein thrombosis (DVT) after orthopedic surgery.Methods:According to random method, 90 patients with DVT after orthopedic surgery who met inclusion criteria in the hospital were divided into two groups between January 2018 and December 2020, 45 cases in each group. Both groups were given DVT catheterization for thrombolysis. After that, control group was given subcutaneous injection of low molecular weight heparin calcium, while observation group was additionally treated with Fumai Zhuyu Decoction. All were continuously treated for 14d. Before and after treatment, scores of TCM syndromes were evaluated. The coagulation response time (R), clotting time (K), clotting angle (α) and maximum strength of blood clotting (MA) were detected by full-automatic thromboelastometry analyzer. The levels of serum IL-6 and CRP were detected by ELISA. The hematocrit (Hct) was calculated according to red cell casts and whole blood height. The adverse reactions were recorded. And the clinical curative effect was evaluated.Results:The differences in total response rate between observation group and control group were statistically significant [82.2% (37/45) vs. 62.2% (38/45); χ2=4.49, P=0.034]. After treatment, scores of affected limb pain, dark encrusted skin and affected limb swelling in observation group were significantly lower than those in control group ( t values were 7.26, 7.14, 6.88, respectively, all Ps<0.001). After treatment, R [(6.12±0.86) min vs. (5.45±0.56) min, t=3.58] and K [(2.24±0.45) min vs. (1.72±0.42) min, t=4.63] in observation group were significantly longer than those in control group ( P<0.01), α [(51.69±2.23)° vs. (54.23±2.42)°, t=4.23] and MA [(51.58±3.62) min vs. (54.58±3.53) min, t=3.25] were significantly lower than those in control group ( P<0.01), and levels of serum IL-6, CRP and Hct were significantly lower than those in control group ( t values were 2.66, 2.96, 7.58, respectively, all Ps<0.01). During treatment, differences in incidence of adverse reactions between observation group and control group were statistically significant [6.7% (3/45) vs. 22.2% (10/45); χ2=4.41, P=0.036]. Conclusion:The Fumai Zhuyu Decoction can reduce blood viscosity, prevent thrombosis and improve clinical curative effect in patients with DVT after orthopedic surgery.

Clinical Efficacy of Dahuang Zhuyu Decoction for Oral Administration and Enema on Severe Acute Pancreatitis with Syndromes of Blood Stasis, Toxin and Its Effect on Serum Inflammatory Factors / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of Dahuang Zhuyu decoction for oral administration and enema on severe acute pancreatitis with syndromes of blood stasis and toxin and its effect on serum inflammatory factors. Method::Sixty eight patients with severe acute pancreatitis with syndromes of blood stasis and toxin who were admitted in Henan Provincial People's Hospital from September 2017 to December 2018 were randomly divided into treatment group (34 cases) and control group (34 cases). The control group was treated with western medicine. The treatment group was treated with Dahuang Zhuyu decoction for oral administattion and enema in addition to the therapy of the control group. Both groups were treated for 7 days. Before and after treatment, abdominal pain, bloating, nausea and vomiting were scored separately, serum amylase (AMS), lipase (LPS), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) were detected, and abdominal pain disappearance time, bloating disappearance time and exhaust recovery time were recorded. Result::After treatment, the abdominal pain score, abdominal distension score, nausea and vomiting score, serum AMS, LPS, IL-6 and TNF-α were lower than those before treatment (P<0.05), and those in treatment group was lower than those in control group (P<0.05). After treatment, IL-10 level in both groups was higher than those before treatment (P<0.05), and that in treatment group was higher than that in control group (P<0.05). The disappearance time of abdominal pain, the disappearance time of abdominal distension and the recovery time of exhaust were shorter in treatment group than in control group (P<0.05). The total effective rate of the treatment group was higher than that of the control group (P<0.05). Conclusion::Dahuang Zhuyu decoction for oral administration and enema for severe acute pancreatitis with syndromes of blood stasis and toxin can alleviate clinical symptoms, reduce amylase and lipase levels, inhibit the expression of pro-inflammatory factors, promote the expression of anti-inflammatory factors, restore intestinal function, and improve clinical efficacy.

Clinical observation on prevention of chemotherapy infection in gastric cancer by moxa-stick moxibustion plus rhG-CSF and its effect on immune function / 针灸推拿医学（英文版）

Objective: To observe the effect of moxa-stick moxibustion plus recombinant human granulocyte-colony stimulating factor (rhG-CSF) in preventing chemotherapy infection in gastric cancer and its effect on immune function. Methods: A total of 70 patients with gastric cancer treated by chemotherapy were randomly divided into an observation group and a control group, with 35 cases in each group. The control group was given rhG-CSF, and the observation group was given additional moxa-stick moxibustion on the basis of rhG-CSF. Both groups were treated for 2 chemotherapy cycles, totally 6 weeks. The number of patients with infection, the duration of infection and the duration of continuous use of antibiotics were observed. The leukocytes and granulocytes counts, the levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured before and after treatment, and the levels of CD4, CD8 and natural killer (NK) cells were analyzed. Results: The infection rate of the observation group was significantly lower than that of the control group (P<0.05), and the duration of infection and the duration of continuous use of antibiotics were also shorter (P<0.05). After treatment, the leukocytes and granulocytes counts in the two groups were higher than those before treatment (all P<0.05). After treatment, the levels of TNF-α and IFN-γ of the patients in the two groups were improved (all P<0.05), and there were significant differences between the observation group and the control group (P<0.05). After treatment, the numbers of CD4, CD8, and NK cells in the observation group increased significantly (all P<0.05), but the changes in the control group were not significant (P>0.05). Conclusion: Moxa-stick moxibustion plus rhG-CSF can significantly reduce the incidence and severity of chemotherapy infection in gastric cancer, increase the leukocytes and granulocytes counts, and regulate the levels of inflammatory factors, which may be related to the improvement of the immune function of the patients.

Network meta-analysis on effectiveness of fire needle, warm acupuncture, and electroacupuncture in the treatment of knee osteoarthritis / 中国组织工程研究

BACKGROUND: Acupuncture has different forms as a kind of therapy, mainly warm acupuncture, fire needle and electroacupuncture, but the balance of effectiveness and safety between these measures remains unclear. OBJECTIVE: To compare the effectiveness of warm acupuncture, fire needle and electroacupuncture in the intervention of knee osteoarthritis by network meta-analysis. METHODS: The Embase, Cochrane Library, PubMed, CNKI, Wanfang, VIP and CBMdisc databases were searched for the clinical randomized controlled trials of warm acupuncture, fire needle and electroacupuncture in the treatment of knee osteoarthritis published before September 20, 2019. RevMan 5.3 and Stata 14.0 were used for data analysis. RESULTS AND CONCLUSION: A total of 2 871 patients with knee osteoarthritis were included in 34 randomized controlled trials. The results of meta-analysis showed that (1) the total clinical effective rate in the fire needle group (OR=1.08, 95%CI: 1.00-1.17, P < 0.05) and warm acupuncture group (OR=1.08, 95%CI: 1.02-1.14, P < 0.05) was better than that in the electroacupuncture, and the total effective rate of the three acupuncture treatments was better than that of western medicine, especially fire needle. (2) In the aspect of improving the Visual Analogue Scale scores, the fire needle (MD=-2.12, 95%CI: -3.52 to -0.71, P < 0.05), warm acupuncture (MD=-1.31, 95%CI: -2.33 to -0.29, P < 0.05), and electroacupuncture (MD=-1.17, 95%CI: -2.19 to -0.16), P < 0.05) were superior to western medicine, especially fire needle. (3) In terms of reducing WOMAC scores, fire needle (MD=-15.38, 95%CI: -27.88 to -2.87, P < 0.05), warm acupuncture (MD=-11.48, 95%CI: -16.45 to -6.51, P < 0.05), and electroacupuncture (MD=-7.29, 95%CI: -11.86 to -2.72, P < 0.05) were superior to western medicine, especially fire needle. (4) In summary, comprehensive comparison of three kinds of acupuncture, in the treatment of knee osteoarthritis, fire needle is the first choice. However, it still needs to be confirmed by more high-quality randomized controlled trials.

Screening of monomers from traditional Chinese medicine for specifically inhibiting brafV600E CT26 cells / 中国药理学通报

Aim: To screen BRAFV600E CT26 cell inhibitors from monomers of traditional Chinese medicine (TCM). Methods CT26 cell line was constructed with lentivirus plasmid to stably express BRAFV6C0E. The proliferation, migration and expression of related proteins in MEK/ERK signaling pathway were detected. The monomers of TCM were detected for biological activities as potential BRAF inhibitors by Discovery Studio 4. 0, and further evaluated by MTT assay. Results: The proliferation and migration of BRAFV6C0E CT26 cells were obviously strengthened compared with wild type control. The expressions of proteins in MEK/ ERK pathway were also activated in BRAFV6C0E CT26 cells. Compared with wild type control, Aloin, Angoroside C and Cyasterone exhibited the potent effect against BRAFV600E in CT26 cells (P <0. 05), and could down-regulate the expression of BRAFV600E. Conclusion: Aloin, Angoroside C, Cyasterone might be the potent inhibitors against BRAF for colon treatment.

Effect of Liuweibuqi capsules on CD4+CD25+Foxp3+ regulatory T cells, helper T cells and lung function in patients with stable chronic obstructive pulmonary disease complicated with lung Qi deficiency.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is predicted to become the fifth leading cause of disability and the third leading cause of death around the world by 2020. Though it is potentially treatable and preventable, evidence of brain structural alterations in COPD remains sparse and conflicting. We aim to investigate the effect of Liuweibuqi capsules on CD4+CD25+ Forkhead box protein 3+ (Foxp3+) regulatory T cells (Tregs), helper T cells (Th) and lung function in patients with stable COPD complicated with lung Qi deficiency. METHODS: COPD patients with lung Qi deficiency [458] were assigned into non-smoking COPD (NS-COPD), non-smoking control (NS-control), smoking COPD (S-COPD) and smoking control (S-control) groups, and healthy volunteers [245] into the non-smoking healthy (NSH) and smoking healthy (SH) groups. Levels of inflammatory cytokines were detected by Enzyme-linked immunoassay (ELISA). Contents of inflammatory cells, inflammatory marker, and CD4+CD25+Fox3+Tregs were measured by flow cytometry. FEV1/FVC (%) and FEV1 (%) were detected by pulmonary function test apparatus. Correlation between FEV1 (%) and Th1, Th2, Th17, Th1/Th2 or CD4+CD25+Fox3+Tregs was analyzed by Spearman rank correlation test. The related factors affecting treatment efficacy was assessed by logistic analysis. RESULTS: COPD patients and smoking people showed higher level of INF-γ, IL-4, IL-17, Th1, Th2, Th17 and Th1/Th2 but lower level of CD4+CD25+Fox3+Tregs. Liuweibuqi capsules could decrease level of inflammatory cells, cytokines, and markers (especially Th17 and IL-17), and increase level of CD4+CD25+Fox3+Tregs. FEV1 (%) negatively correlated with Th1, Th2, Th17 and Th1/Th2 but positively correlated with CD4+CD25+Fox3+Tregs, and smoking may strengthen their correlation, but Liuweibuqi capsules may weaker their correlation. Levels of inflammatory cytokines, cells, marker, CD4+CD25+Fox3+Tregs, FEV1/FVC (%), FEV1 (%), smoking and Liuweibuqi capsules are factors affecting efficacy. CONCLUSIONS: Taken together, our data support the notion that smoking is an important factor to induce and aggravate COPD. Liuweibuqi capsules could stimulate proliferation of CD4+CD25+Fox3+Tregs and decrease Th17 expression to improve the lung function in stable COPD patients with lung Qi deficiency, and it had obvious efficacy for smoking COPD patients.

Comparative analysis of immune function, hemorheological alterations and prognosis in colorectal cancer patients with different traditional Chinese medicine syndromes.

OBJECTIVE: The present study investigates the differences in immune function, hemorheological alterations and prognostic evaluation in colorectal cancer (CRC) patients with different traditional Chinese medicine (TCM) syndromes. METHODS: A total of 128 patients, diagnosed as stage II and III of CRC, were recruited. They were assigned into three TCM syndromes: deficiency syndrome, excess syndrome, and syndrome of intermingled deficiency and excess, and another 53 healthy individuals were selected as the control. Flow cytometry was used to determine the peripheral blood lymphocyte subsets (the levels of CD+3, CD+4, CD+8, NK cells, and the ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2). Whole blood viscosity (WBV), plasma viscosity (PV), hematocrit (Hct), erythrocyte sedimentation rate (ESR), plasma fibrinogen concentration (PFC) were measured using a fully-automatic blood rheological instrument. The univariate analysis and Cox regression analysis were conducted to evaluate the prognosis of CRC patients with different TCM syndromes. RESULTS: Compared with healthy individuals, CRC patients with three different syndromes had lower levels of CD+3, CD+4, NK cells, and ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2, but higher level of CD+8, WBV, PV, Hct, ESR and PFC. Besides, patients with excess syndrome showed the highest levels of CD3+, CD4+ and NK cells, and ratios of CD+4/CD+8, Th1/Th2 and Tc1/Tc2, but the lowest level of CD+8 among three syndromes, and those with deficiency syndrome showed an opposite trend. Compared with patients with excess syndrome, those with deficiency syndrome showed decreased WBV, PV, Hct, ESR and PFC. The pathological type, surgical approach, tumor node metastasis (TNM) stage, liver metastasis, TCM treatment time and different TCM syndromes were independent factors of prognostic survival in CRC patients except perioperative blood transfusion volume. CONCLUSIONS: Taken together, we conclude that patients with TCM deficiency syndrome has lower immune function and poorer prognosis while patients with TCM excess syndrome has higher immune function and better prognosis of CRC.

Effect of mindfulness training intervention on cancer related fatigue after chemotherapy in patients with breast cancer / 重庆医学

Objective To investigate the effects of mindfulness training on cancer related fatigue (CRF) in patients with breast cancer .Methods Two hundreds young and middle‐aged patients with breast cancer receiving chemotherapy in our hospital from January to June 2015 were divided into the observation group and control group ,100 cases in each group .The control group was given the routine nursing ,while on this basis the observation group was given the mindfulness training .The cancer related fa‐tigue status was evaluated according to the CFS scale .The CFS various dimensions and total fatigue scores before and after inter‐vention were compared between the two groups .Results The fatigue status existed in most of patients with breast cancer after chemotherapy ,the occurrence rate of CRF was 97 .0% ,which was dominated by moderate fatigue ,followed by mild fatigue ,severe fatigue was minimal ;the body fatigue ,cognitive fatigue ,emotional fatigue and total fatigue scores in the second time of chemothera‐py had no statistically significant differences between the two groups (P>0 .05);in the fourth and sixth time of chemotherapy ,the body fatigue ,cognitive fatigue ,emotional fatigue and total fatigue scores in the observation group were significantly lower than those in the control group ,the differences were statistically significant (P<0 .05) .Conclusion The mindfulness training interven‐tion can relieve the fatigue status and improve the living quality of the patient .

Bruising caused by traditional Chinese massage therapy (ba sha) complicating the assessment of a case of fatal child abuse.

Precise evaluation of bruises and patterned skin lesions in infants and children is an essential requirement in cases of potential abuse. Such injuries may be markers of more significant internal injuries and/or may be supportive of an assault rather than an accident. On occasion, however, unusual patterned skin lesions may be identified that have been inflicted as part of traditional therapeutic techniques. A five-year-old boy from a rural Chinese community is reported who died from ligature strangulation. In addition to bruises from abusive trauma he had a series of unusual patterned, often-paired, bruises over the anterior and posterior aspects of both shoulders, unrelated to the ligature mark. Upon further police inquiries it transpired that his grandmother and mother had been using traditional Chinese therapeutic massage or "ba sha" to treat an episode of vomiting. The term means "to pull out fever" and involves firm pinching of the skin between the thumb and index finger, often on the neck, chest or back. An awareness of the potential manifestations of traditional therapies is important in contemporary forensic practice so that injuries caused by these treatments are not confused with non-therapeutic inflicted injury.

Higher antiviral response of RIG-I through enhancing RIG-I/MAVS-mediated signaling by its long insertion variant in zebrafish.

As an intracellular pattern recognition receptor (PRR), the retinoic acid-inducible gene-I (RIG-I) is responsible for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). In the present study, an insertion variant of RIG-I with 38 amino acids inserted in the N-terminal CARD2 domain, as well as the typical type, named as RIG-Ia and RIG-Ib respectively were identified in zebrafish. RIG-Ia and RIG-Ib were all up-regulated following the infection of a negative ssRNA virus, the Spring Viremia of Carp Virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, indicating the RLR may have a role in the recognition of both viruses and bacteria. The over-expression of RIG-Ib in cultured fish cells resulted in significant increase in type I IFN promoter activity, and in protection against SVCV infection, whereas the over-expression of RIG-Ia had no direct effect on IFN activation nor antiviral response. Furthermore, it was revealed that both RIG-Ia and RIG-Ib were associated with the downstream molecular mitochondrial antiviral signaling protein, MAVS, and interestingly RIG-Ia when co-transfected with RIG-Ib or MAVS, induced a significantly higher level of type I IFN promoter activity and the expression level of Mx and IRF7, implying that the RIG-Ia may function as an enhancer in the RIG-Ib/MAVS-mediated signaling pathway.

Compound Tufuling Granules (characters: see text) regulate glucose transporter 9 expression in kidney to influence serum uric acid level in hyperuricemia mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effect of Compound Tufuling Granules ([characters: see text], CTG) on regulating glucose transporter 9 (GLUT9) expression in the kidney to influence the uric acid excretion by the kidney and serum uric acid (SUA) level in hyperuricemia mice.</p><p><b>METHODS</b>Sixty Kunming male mice were randomly divided into the control group, model group, benzbromarone group, and CTG high-, middle- and low-dose groups. The yeast extract and uricase inhibition method were used to build hyperuricemia model, and the corresponding drugs were administrated on the 7th day. On the 21st day the 24-h urine was collected, on the 22nd day the blood was collected, the SUA level was detected by uricase colorimetry, and the mRNA and protein expressions of GLUT9 were detected by quantitative real-time polymerase chain reaction and Western blot, respectively.</p><p><b>RESULTS</b>Compared with the model group, the levels of SUA and the mRNA and protein expressions of GLUT9 were significantly decreased, and the fraction excretion of uric acid (FEUA) was significantly increased in the CTG groups and benzbromarone group (all P<0.05). There was no significant difference in the above indicators between the CTG high-dose group and benzbromarone group (P>0.05). SUA is positively related to the GLUT9 mRNA and protein expressions in the kidney (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>CTG can significantly reduce the SUA and increase the FEUA. In addition, CTG can effectively inhibit the mRNA and protein expressions of GLUT9 in the kidney of hyperuricemia mice to inhibit the uric acid re-absorption, promote uric acid excretion and reduce SUA.</p>

Inhibitory effects of propofol on supraoptic nucleus neurons of rat hypothalamus in vitro / 生理学报

To investigate the effects of novel intravenous general anesthetic propofol on membrane electrophysiological characteristics and action potential (AP) of the supraoptic nucleus (SON) neurons and possible ionic mechanisms, intracellular recordings were conducted in SON neurons from the coronal hypothalamic slice preparation of adult male Sprague Dawley (SD) rats. The results showed that bath application of 0.1 mmol/L propofol induced a significant decline in resting potential (P < 0.01), and higher concentrations of propofol (0.3 and 1.0 mmol/L) decreased time constant and slope resistance of cell membrane (P < 0.01). Under the hyperpolarizing current pulses exceeding 0.5 nA, an anomalous rectification was induced by hyperpolarization-activated cation channel (I(h) channel) in 11 out of 18 tested SON neurons. Bath of propofol reversibly decreased the anomalous rectification. Moreover, 0.1 mmol/L propofol elevated threshold level (P < 0.01) and decreased Max L. slope (P < 0.05) of the spike potential in SON neurons. Interestingly, 0.3 and 1.0 mmol/L propofol nullified APs in 6% (1/18) and 71% (12/17) tested SON neurons, respectively. In the SON neurons where APs were not nullified, propofol (0.3 mmol/L) decreased the amplitude of spike potential (P < 0.05). The higher concentrations of propofol (0.3 and 1.0 mmol/L) decreased firing frequencies evoked by depolarizing current pulses (0.1-0.7 nA), and shifted the current intensity-firing frequency relation curves downward and to the right. These results suggest that propofol decreases the excitability of SON neurons by inhibiting I(h) and sodium channels.

Pharmacophore modeling and hybrid virtual screening for the discovery of novel IκB kinase 2 (IKK2) inhibitors.

IKK2 (IκB kinase 2) inhibitors have been identified as potential drug candidates in the treatment of various immune/inflammatory disorders as well as cancer. So far more than one hundred small molecule inhibitors against IKK2 have been reported publicly. In this investigation, pharmacophore modeling was carried out to clarify the essential structure-activity relationship for the known IKK2 inhibitors. One of the established pharmacophore hypotheses, namely Hypo8, which has the best prediction ability to an external test data set, was suggested as a template for virtual screening. Evaluation of the performances of Hypo8 and a hybrid method (Hypo81docking) in virtual screening indicated that the use of the hybrid virtual screening considerably increased the hit rate and enrichment factor. The hybrid method was therefore adopted for screening several commercially available chemical databases, including Specs, NCI, Maybridge and Chinese Nature Product Database (CNPD), for novel potent IKK2 inhibitors. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five. Finally some of the final hit compounds were selected and suggested for further experimental investigations.

Discovery of novel Pim-1 kinase inhibitors by a hierarchical multistage virtual screening approach based on SVM model, pharmacophore, and molecular docking.

In this investigation, we describe the discovery of novel potent Pim-1 inhibitors by employing a proposed hierarchical multistage virtual screening (VS) approach, which is based on support vector machine-based (SVM-based VS or SB-VS), pharmacophore-based VS (PB-VS), and docking-based VS (DB-VS) methods. In this approach, the three VS methods are applied in an increasing order of complexity so that the first filter (SB-VS) is fast and simple, while successive ones (PB-VS and DB-VS) are more time-consuming but are applied only to a small subset of the entire database. Evaluation of this approach indicates that it can be used to screen a large chemical library rapidly with a high hit rate and a high enrichment factor. This approach was then applied to screen several large chemical libraries, including PubChem, Specs, and Enamine as well as an in-house database. From the final hits, 47 compounds were selected for further in vitro Pim-1 inhibitory assay, and 15 compounds show nanomolar level or low micromolar inhibition potency against Pim-1. In particular, four of them were found to have new scaffolds which have potential for the chemical development of Pim-1 inhibitors.

Arterial embolization hyperthermia using As2O3 nanoparticles in VX2 carcinoma-induced liver tumors.

BACKGROUND: Combination therapy for arterial embolization hyperthermia (AEH) with arsenic trioxide (As(2)O(3)) nanoparticles (ATONs) is a novel treatment for solid malignancies. This study was performed to evaluate the feasibility and therapeutic effect of AEH with As(2)O(3) nanoparticles in a rabbit liver cancer model. The protocol was approved by our institutional animal use committee. METHODOLOGY/PRINCIPAL FINDINGS: In total, 60 VX(2) liver-tumor-bearing rabbits were randomly assigned to five groups (n = 12/group) and received AEH with ATONs (Group 1), hepatic arterial embolization with ATONs (Group 2), lipiodol (Group 3), or saline (Group 4), on day 14 after tumor implantation. Twelve rabbits that received AEH with ATONs were prepared for temperature measurements, and were defined as Group 5. Computed tomography was used to measure the tumors' longest dimension, and evaluation was performed according to the Response Evaluation Criteria in Solid Tumors. Hepatic toxicity, tumor necrosis rate, vascular endothelial growth factor level, and microvessel density were determined. Survival rates were measured using the Kaplan-Meier method. The therapeutic temperature (42.5°C) was obtained in Group 5. Hepatotoxicity reactions occurred but were transient in all groups. Tumor growth was delayed and survival was prolonged in Group 1 (treated with AEH and ATONs). Plasma and tumor vascular endothelial growth factor and microvessel density were significantly inhibited in Group 1, while tumor necrosis rates were markedly enhanced compared with those in the control groups. CONCLUSIONS: ATON-based AEH is a safe and effective treatment that can be targeted at liver tumors using the dual effects of hyperthermia and chemotherapy. This therapy can delay tumor growth and noticeably inhibit tumor angiogenesis.

[The feasibility of application of reverse docking method to the selectivity studies of protein kinase inhibitors].

This investigation is to explore the feasibility of applying reverse docking method to the selectivity studies of protein kinase inhibitors. Firstly, a database that consists of 422 protein kinase structures was established through collecting the reported crystal structures or homology modeling. Then a reverse docking based method of protein kinase target screening was established, followed by the optimization of related parameters and scoring functions. Finally, seven typical selective kinase inhibitors were used to test the established method. The results show that the selective targets of these inhibitors have relatively high scoring function values (ranking in the first 35% of the tested kinase targets according to the scoring function values). This implies that the reverse docking method can be applied to the virtual screening of kinase targets and further to the selectivity studies of protein kinase inhibitors.

The feasibility of application of reverse docking method to the selectivity studies of protein kinase inhibitors / 药学学报

This investigation is to explore the feasibility of applying reverse docking method to the selectivity studies of protein kinase inhibitors. Firstly, a database that consists of 422 protein kinase structures was established through collecting the reported crystal structures or homology modeling. Then a reverse docking based method of protein kinase target screening was established, followed by the optimization of related parameters and scoring functions. Finally, seven typical selective kinase inhibitors were used to test the established method. The results show that the selective targets of these inhibitors have relatively high scoring function values (ranking in the first 35% of the tested kinase targets according to the scoring function values). This implies that the reverse docking method can be applied to the virtual screening of kinase targets and further to the selectivity studies of protein kinase inhibitors.

Effects of acupuncture and moxibustion on DNA excision repair-related proteins of bone marrow cell in cyclophosphamide-induced mice / 中国针灸

<p><b>OBJECTIVE</b>To explore the molecular biological mechanism of acupuncture and moxibustion for relieving myelosuppression and increasing white blood cells.</p><p><b>METHODS</b>Two hundred and twenty-four clean male Kunming mice were randomly divided into a control group, a model group, an acupuncture group and a moxibustion group, 56 mice in each group. The model of myelosuppression was made with Cyclophosphamide. In the acupuncture group and the moxibustion group, acupoints "Dazhui" (GV 14), "Geshu" (BL 17), "Shenshu" (BL 23) and "Zusanli" (ST 36) were used for treatment with acupuncture and moxibustion, respectively, while, in the control group and the model group, there were no treatment carried out except catching and fixing. The changes of bone marrow cell DNA pol beta and XPD between the 2nd and 7th day were examined with immunohistochemical method.</p><p><b>RESULTS</b>Acupuncture and moxibustion markedly up-regulated the expression of bone marrow cell DNA pol beta and XPD, and promoted the base excision repair and nucleotide excision repair, which leads to the relieving Cyclophosphamide-induced myelosuppression and increasing the number of white blood cells.</p><p><b>CONCLUSION</b>For acupuncture and moxibustion, one of the bone major mechanisms in relieving post-chemotherapy myelosuppression, protecting hemopoietic function and increasing the white blood cells is that it can promote the repair of the bone marrow cell DNA excision and protect hemopoietic cells from injury by chemical drugs.</p>