Mogrol suppresses lung cancer cell growth by activating AMPK-dependent autophagic death and inducing p53-dependent cell cycle arrest and apoptosis.

Lung carcinoma is the leading cause of cancer-related death worldwide. Chemotherapy remains the cornerstone of lung cancer treatment. Unfortunately, most types of cancer will develop resistance to chemotherapies over the time. One of the efforts to prevent the chemotherapy resistance is to find alternative chemotherapy drugs. Mogrol has been found to have antitumor activity. However, little is known about the pharmacological mechanisms underlying the suppression of mogrol on lung cancers. In this study, we observed that mogrol exposure significantly reduced the tumor volume and weight in tumor-bearing nude mice without obvious effect on body weight and cardiac function. Mogrol also significantly inhibited the proliferation and migration of lung cancer cells, including non-small-cell lung carcinoma cells, A549, H1299, H1975 and SK-MES-1 cells, with no obvious effect on control human bronchial epithelial cells (HBE). Further studies revealed that mogrol stirred excessive autophagy and autophagic flux, and finally, autophagic cell death, in lung cancer cells, which could be attenuated by autophagy inhibitors, 3-MA and chloroquine. Furthermore, mogrol significantly activated AMPK to induce autophagy and autophagic cell death, which could be abrogated by Compound C, an AMPK inhibitor. In addition, mogrol induced a significant increase in p53 activity in lung cancer cells, accompanied with cell cycle arrest and apoptosis, which could be weakened by p53 silence. Our results indicated that mogrol effectively suppressed lung cancer cells in vivo and in vitro by inducing the excessive autophagy and autophagic cell death via activating AMPK signaling pathway, as well as cell cycle arrest and apoptosis via activating p53 pathway.

Irisin alleviates pressure overload-induced cardiac hypertrophy by inducing protective autophagy via mTOR-independent activation of the AMPK-ULK1 pathway.

In hypertrophic hearts, autophagic flux insufficiency is recognized as a key pathology leading to maladaptive cardiac remodeling and heart failure. This study aimed to illuminate the cardioprotective role and mechanisms of a new myokine and adipokine, irisin, in cardiac hypertrophy and remodeling. Adult male wild-type, mouse-FNDC5 (irisin-precursor)-knockout and FNDC5 transgenic mice received 4 weeks of transverse aortic constriction (TAC) alone or combined with intraperitoneal injection of chloroquine diphosphate (CQ). Endogenous FNDC5 ablation aggravated and exogenous FNDC5 overexpression attenuated the TAC-induced hypertrophic damage in the heart, which was comparable to the protection of irisin against cardiomyocyte hypertrophy induced by angiotensin II (Ang II) or phenylephrine (PE). Accumulated autophagosome and impaired autophagy flux occurred in the TAC-treated myocardium and Ang II- or PE-insulted cardiomyocytes. Irisin deficiency caused reduced autophagy and aggravated autophagy flux failure, whereas irisin overexpression or supplementation induced protective autophagy and improved autophagy flux, which were reversed by autophagy inhibitors Atg5 siRNA, 3-MA and CQ. Irisin boosted the activity of only AMPK but not Akt and MAPK family members in hypertrophic hearts and cultured cardiomyocytes and further activated ULK1 at Ser555 but not Ser757 and did not affect the mTOR-S6K axis. Blockage of AMPK and ULK1 with compund C and SBI-0206965, respectively, both abrogated irisin's protection against cardiomyocyte hypertrophic injury and reversed its induction of both autophagy and autophagy flux. Our results suggest that irisin protects against pressure overload-induced cardiac hypertrophy by inducing protective autophagy and autophagy flux via activating AMPK-ULK1 signaling.

Video texture synthesis based on flow-like stylization painting.

The paper presents an NP-video rendering system based on natural phenomena. It provides a simple nonphotorealistic video synthesis system in which user can obtain a flow-like stylization painting and infinite video scene. Firstly, based on anisotropic Kuwahara filtering in conjunction with line integral convolution, the phenomena video scene can be rendered to flow-like stylization painting. Secondly, the methods of frame division, patches synthesis, will be used to synthesize infinite playing video. According to selection examples from different natural video texture, our system can generate stylized of flow-like and infinite video scenes. The visual discontinuities between neighbor frames are decreased, and we also preserve feature and details of frames. This rendering system is easy and simple to implement.

An Optimized LIME Scheme for Medical Low Light Level Image Enhancement.

The role of medical image technology in the medical field is becoming more and more obvious. Doctors can use medical image technology to more accurately understand the patient's condition and make accurate judgments and diagnosis and treatment in order to make a large number of medical blurred images clear and easy to identify. Inspired by the human vision system (HVS), we propose a simple and effective method of low-light image enhancement. In the proposed method, first a sampler is used to get the optimal exposure ratio for the camera response model. Then, a generator is used to synthesize dual-exposure images that are well exposed in the regions where the original image is underexposed. Next, the enhanced image is processed by using a part of low-light image enhancement via the illumination map estimation (LIME) algorithm, and the weight matrix of the two images will be determined when fusing. After that, the combiner is used to get the synthesized image with all pixels well exposed, and finally, a postprocessing part is added to make the output image perform better. In the postprocessing part, the best gray range of the image is adjusted, and the image is denoised and recomposed by using the block machine 3-dimensional (BM3D) model. Experiment results show that the proposed method can enhance low-light images with less visual information distortions when compared with those of several recent effective methods. When it is applied in the field of medical images, it is convenient for medical workers to accurately grasp the details and characteristics of medical images and help medical workers analyze and judge the images more conveniently.

Prim-O-glucosycimifugin attenuates liver injury in septic mice by inhibiting NLRP3 inflammasome/caspase-1 signaling cascades in macrophages.

BACKGROUND: Liver dysfunction and liver failure are serious complications of sepsis, directly leading to septic progression and death. Now, there is no specific therapeutics available for sepsis-related liver dysfunction. Prim-O-glucosylcimifugin (POG), a chromone richest in the roots of Saposhnikovia divaricata (Turcz.) Schischk, is usually used to treat headache, rheumatoid arthritis and tetanus. While, the underlying mechanisms of POG against sepsis-induced liver damage and dysfunction are still not clear. PURPOSE: To study the anti-sepsis effect of POG, and its pharmacological mechanism to protect liver injury by weakening the function of macrophages in septic livers through inhibiting NOD-like receptor protein 3 (NLRP3) inflammasome pathway. METHOD: In vivo experiments, septic mouse model was induced by cecal ligation and puncture (CLP), and then the mortality was detected, liver inflammatory damages and plasma biomarkers of liver injury were evaluated by histopathological staining and biochemical assays, respectively. In vitro experiments, mouse primary peritoneal macrophages were treated with lipopolysaccharide (LPS) and ATP, and then the activated-inflammasomes, macrophage migration and polarization were detected by ASC immunofluorescence staining, transwell and flow cytometry assays, respectively. NLRP3 inflammasome components NLRP3, caspase-1, IL-1ß and IL-18 protein expressions were detected using western blot assays, and the contents of IL-1ß and IL-18 were measured by ELISA assays. RESULTS: POG treatment significantly decreased the mortality, liver inflammatory damages, hepatocyte apoptosis and plasma biomarkers of liver injury in CLP-challenged male WT mice, which were comparable to those in ibuprofen (a putative anti-inflammatory drug)-supplemented septic male WT mice and septic NLRP3 deficient-male mice. POG supplementation significantly suppressed NLRP3 inflammasome activation in septic liver tissues and cultured macrophages, by significantly reducing NLRP3, cleaved-caspase-1, IL-1ß and IL-18 levels, the activated-inflammasome ASC specks, and macrophage infiltration and migration, as well as M1-like polarization, but significantly increasing M2-like polarization. These findings were similar to the pharmacological effects of ibuprofen, NLRP3 deficiency, and a special NLRP3 inhibitor, MCC950. CONCLUSION: POG protected against sepsis by inhibiting NLRP3 inflammasome-mediated macrophage activation in septic liver and attenuating liver inflammatory injury, indicating that it may be a potential anti-sepsis drug candidate.

5-Lipoxagenase deficiency attenuates L-NAME-induced hypertension and vascular remodeling.

BACKGROUND: Abnormalities of the L-arginine-nitric oxide pathway induce hypertension. 5-Lipoxygenase (5-LO) is the key enzyme involved in synthesis of leukotrienes (LTs). However, whether nitricoxide synthase dysfunction induces hypertensive vascular remodeling by regulating 5-LO activity and its downstream inflammatory metabolites remains unknown. METHODS AND RESULTS: Six-week L-NAME treatment significantly induced hypertension and vascular remodeling in both wild-type (WT) and 5-LO-knockout (5-LO-KO) mice, and blood pressure in caudal and carotid arteries was lower in 5-LO-KO than WT mice with L-NAME exposure. On histology, L-NAME induced less media thickness, media-to-lumen ratio, and collagen deposition and fewer Ki-67-positive vascular smooth muscle cells (VSMCs) but more elastin expression in thoracic and mesenteric aortas of 5-LO-KO than L-NAME-treated WT mice. L-NAME significantly increased LT content, including LTB4 and cysteinyl LT (CysLTs), in plasma and neutrophil culture supernatants from WT mice. On immunohistochemistry, L-NAME promoted the colocalization of 5-LO and 5-LO-activating protein on the nuclear envelope of cultured neutrophils, which was accompanied by elevated LT content in culture supernatants. In addition, LTs significantly promoted BrdU incorporation, migration and phenotypic modulation in VSMCs. CONCLUSION: L-NAME may activate the 5-LO/LT pathway in immune cells, such as neutrophils, and promote the products of 5-LO metabolites, including LTB4 and CysLTs, which aggravate vascular remodeling in hypertension. 5-LO deficiency may protect against hypertension and vascular remodeling by reducing levels of 5-LO downstream inflammatory metabolites.

Aclinicalstudyontheefficacyandsafetyofmodifiedaspirationcatheterinthetreatment ofacutelowerextremitydeepveinthrombosis / 实用放射学杂志

Objective Toinvestigatethethrombusclinicalcurativeeffectandpracticalvalueintreatmentofdeepveinthrombosis (DVT)byusingmodifiedaspirationcatheter.Methods Atotalof35patientswhometthediagnosticcriteriaofDVTwererandomly assignedintoexperimentalandcontrolgroups.Afterasufficientpreoperativepreparation,thepatientsweredividedintotheexperimentalgroup (n=18,usingmodifiedaspirationcatheterwithsubsequenturokinasethrombolysisandconventionalanticoagulationtherapy)andthe controlgroup [n=17,usingthe8Fvascularsheaths (COOK,USA)duringtheprocedure,subsequenturokinasethrombolysisand conventionalanticoagulationtherapy].Thepatencyofvessels,theperimeterdifferenceandthecomplicationweredocumented.Theresultswere comparedbetweenthetwogroups.Results Inexperimentalgroup,thrombusremovalofgradeⅣ (removalratelessthan0%)was 0%in0case,gradeⅢ (removalratelessthan50%)was5.56%in1case,gradeⅡ (removalrategreaterthan50%)was94.44%in ncontrolgroup,thrombusremovalofgradeⅣwas23.53%in4cases,gradeⅢwas52.94%in9cases,gradeⅡwas23.53%in4cases. Thedifferencesofthelegcircumferenceoftheaffectedextremitiesat15cmaboveandbelowthekneejointattimeofdischargewere alllessthanthoseatadmission.Thedifferencesinbothpreoperativeandpostoperativedatabetweenthetwogroupswerestatistically significant(bothP<0.05).Noseriouscomplicationswerefoundintwogroups.Conclusion UsingmodifiedaspirationcathetertreatingDVTisa safeandeffectivemethod,whichhashighsuctionefficiencyandfewcomplications.Therefore,itisworthytoberecommended. 17casesI.

Clinical curative effect analysis of vena cava filter placement and thrombolytic therapy combined with Rivaroxaban for acute deep venous thrombosis / 实用放射学杂志

Objective To analyze the clinical curative effect of inferior vena cava filter placement and catheter direct thrombolytic therapy combined with anticoagulant therapy with Rivaroxaban for deep venous thrombus (DVT) of the lower extremity.Methods 40 patients with acute lower extremity DVT were collected,after the inferior vena cava filter placement,thrombolytic catheter were placed in femoral and iliac vein occlusion,and urokinase was continuously infused through the catheter 24 h.Anticoagulant therapy with Rivaroxaban tablets started when the patient was diagnosed with the disease.We evaluated the short-term and long-term efficacy of the treatment from the iliac femoral vein patency,limb circumference and complications.Results 40 patients were successfully implanted the filter,38 patients were successfully removed the filter after 21 days.The clinical symptoms were relieved after 7 days of treatment,and the iliac femoral vein blood flow was basically recovered.Before and after treatment,the limb circumference was significantly reduced (P＜0.05).No serious complications occurred during the treatment period.Following up in 6 months,the rate of iliac vein occlusion and pigmentation were 2.5 ％ (1/40)and 2.5 ％ (1/40)respectively.Following up in 12 months,the rate of iliac vein occlusion and pigmentation were 7.5 ％ (3/40) and 5.0 ％ (2/40)respectively.Conclusion For treatment of acute DVT of the lower extremity,inferior vena cava filter placement and catheter direct thrombolytic therapy combined with anticoagulant therapy with Rivaroxaban can achieve satisfactory clinical curative effect,which is clinically safe and feasible.

Design and application of information management system of nuclear medicine / 中华核医学与分子影像杂志

Information management system of nuclear medicine (IMSNM) is an important part of modem medical information system.It is used for the scientific management of clinical works,and classification and storage of patient data and examination data (words and images).With the help of IMSNM,standardization,automation and digitization of clinical operation protocols,the scientific and normalized management,the unification of image storage and viewing could be achieved.The IMSNM plays an important role in the health care,education and scientific research.This study mainly describes the design and application of IMSNM.

Comparative study on the efficacy and safety of interventional therapy of uterine fibroid using Embosphere and Pingyangmycin lipiodol emulsion / 实用放射学杂志

Objective To observe the curative effect and safety of interventional therapy of uterine fibroids using Embosphere and Pingyangmycin lipiodol emulsion.Methods The clinical data of 120 cases with uterine fibroids treated in our hospital were reviewed,and the patients were according to the different treatments given,divided into two groups (each with 60 cases).Patients in control group were treated with interventional therapy of Pingyangmycin lipiodol emulsion,while patients in the study group were given interventional therapy of Embosphere.The clinical efficacy and safety in the two groups were compared.Results The total efficiency in the study group was 93.33%,which was significantly higher than that in the control group (75.00%),and the difference was statistically significant (P<0.05).The comprehensive indexes after the treatment were improved in both groups compared with those before the treatment,and the improvement in the study group was significantly better than the control group (P<0.05,P<0.01).Besides,the total incidence of adverse effects in the study group was 11.67%,which was significantly lower than that in the control group (26.67%)(P<0.05). Conclusion The interventional therapy using Embosphere has better effect on uterine fibroid compared with the therapy using Pingyangmycin lipiodol emulsion,which is worthwhile to be brought into clinical application.

Cytokeratin expression in cervical lymph nodes of patients with mandibular gingival squamous cell carcinoma / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To examine the cytokeratin expression in cervical lymph nodes of patients with mandibular gingival squamous cell carcinoma and its clinical significance.</p><p><b>METHODS</b>The data of 42 cases with mandibular gingival squamous cell carcinoma after operation from July 2009 to December 2012 were included. Forty-two patients (male = 27, formale = 15) were included, with a mean age of 54.1 years (range 27-77). The lesions were staged (stage I:9, stage II:16, stage III:6, stage IV:11). The cervical lymph nodes were examined by immunohistochemistry and HE. The cytokeratin expression in the lymph nodes was analyzed.</p><p><b>RESULTS</b>The rates of lymph nodes metastasis detected by routine HE staining, serial sections HE staining and IHC were 8.0% (47/585), 9.6% (56/585) and 12.8% (75/585), respectively. There was significant difference (χ(2) = 7.17, P < 0.01) in the diagnosis of lymph nodes metastasis between IHC and routine HE staining, There was no significant difference between IHC and serial HE staining (χ(2) = 3.10, P > 0.05). Metastasis occurred mainly in the Level I, II and III. Nineteen lymph nodes in 12 patients were found micrometastasis with IHC. Serial sections and routine HE staining did not find micrometastasis.</p><p><b>CONCLUSIONS</b>CK markers is sensitive in detecting lymph node metastasis of mandibular gingival squamous cell carcinoma.</p>

Two kinds of uterine artery perfusion chemotherapy plus embolization for the treatment of ectopic pregnancy：a single center, randomized, double-blind and controlled study / 介入放射学杂志

Objective To evaluate the clinical efficacy and safety of two kinds of uterine artery perfusion chemotherapy plus embolization (UACE) in treating ectopic pregnancy (EP). Methods A single center, randomized, double-blind, controlled clinical trial was carried out at authors hospital. A total of 50 cases of EP patients were randomly and equally divided into the study group (perfusion chemotherapy of MTX and 5-FU plus embolization therapy) and the control group (perfusion chemotherapy of pure MTX plus embolization therapy). After UACE, the serumβ-HCG value, the clinical healing time and the tubal patency rate were determined at different time, and the adverse events were recorded. The results were statistically analyzed by using t test, and χ2 test, and the data were compared between the two groups. Results One patient in both groups was excluded from the study. In the remaining 48 patients, one patient of the control group failed to respond the treatment, so the overall cure rate was 97.9%. The differences in the main effect of treatment method and the time interaction of the serum β-HCG values between the two groups were not statistically significant (P > 0.05), while the difference in the time effect between the two groups was statistically significant (P 0.05). The tubal patency rate of the study group and the control group was 76.2%and 78.9%respectively, and no statistically significant difference existed between the two groups (P > 0.05). The adverse events in both groups were mild, and the occurrence of the adverse events in the study group and the control group was 58.3% and 26.1% respectively, and the difference between the two groups was statistically significant (P <0.05). Conclusion Two kinds of interventional methods have the same clinical curative effect. However, the incidence of adverse events in the control group is lower than that in the study group. Therefore, in treating ectopic pregnancy perfusion chemotherapy with MTX only is recommend.

Two novel compounds from Ardisia punctata Lindl / 药学学报

To study the chemical constituents of Ardisia punctata, compounds were isolated with a combination of multi-chromatography. Their structures were determined on the basis of spectral analysis and comparison to those of the known compounds. A 1,4-benzoquinone derivative and a alkylphenol were isolated from the petroleum ether extract of the roots of Ardisia punctata. Their structures were elucidated as 2-tridecyl-3-[(2-tridecyl-4-acetoxy-6-methoxy)-phenoxyl] -6-methoxy-1,4-benzoquinone (1) and 2-methoxy-4-hydroxy-6-tridecyl-phenyl acetate (2). The two compounds are both new.

Chemical constituents from roots of Ficus hirta / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents from the roots of Ficus hirta.</p><p><b>METHOD</b>Compounds were isolated by chromatographic techniques on silica gel and HP-20 resin columns. Their structures were elucidated by chemical and spectroscopic methods.</p><p><b>RESULT</b>Ten compounds were identified as beta-sitosterol (1), stigmasterol (2), psoralene (3), 3beta-hydroxy-stigmast-5-en-7-one (4), 5-hydroxy-4', 6, 7, 8-tetramethoxy flavone (5), 4', 5, 6, 7, 8-pentamethoxy flavone (6), 4', 5, 7-trihydroxy-flavone (7), 3beta-acetoxy-beta-amyrin (8), 3beta-acetoxy-alpha-amyrin (9) and hesperidin (10).</p><p><b>CONCLUSION</b>The compounds 4, 5, 6 were obtained from this genus for the first time, and all the compounds were obtained from this plant for the first time.</p>

Chemical constituents from roots of Ardisia punctata / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents from the roots of Ardisia punctata.</p><p><b>METHOD</b>Compounds were isolated by chromatographic techniques on silica gel and Rp-HPLC column. Their structures were elucidated by chemical and spectroscopic methods.</p><p><b>RESULT</b>Twelve compounds were identified as 3-hydroxy-5-tridecyl-methyl phenyl ether (1), 5-pentadecyl-1, 3-benzenediol (2), 2-methoxy-6-tridecyl-1, 4-benzoquinone (3), 2-methoxy-6-pentadecyl-1, 4-benzoquinone (4), glutinol (5), ardisicrenoside A (6), ardisiacrispin B (7), 24-ethyl-5a-cholesta-7, 22(E)-dien-3-one (8), 24-ethyl-5alpha-cholesta-7, 22(E)-dien-3beta-ol (9), daucosterol (10), vanillin acid (11), tetratriacontanoic acid (12).</p><p><b>CONCLUSION</b>All the compounds were obtained from this plant for the first time.</p>

Three new belamcandaquinones from Ardisia punctata / 药学学报

<p><b>AIM</b>To study the chemical constituents of Ardisia punctata.</p><p><b>METHODS</b>Compounds were separated with a combination of multi-chromatography. Their chemical structures were determined on the basis of spectral analysis and single crystal X-ray diffraction.</p><p><b>RESULTS</b>Three compounds were isolated from chloroform extract of the roots of Ardisia punctata. Their structures were elucidated as 2-tridecyl-3-[(2-tridecyl-3-acetoxy-4-methoxy-6-hydroxy) -phenyl]-6-methoxy-1, 4-benzoquinone (1), 2-tridecyl-3-[(2-tridecyl-4,6-dihydroxy) -phenyl]-6-methoxy-1,4-benzoquinone (2) and 2-tridecyl-3-[(2-pentadecyl-4,6-dihydroxyl) -phenyl]-6-methoxy-,4-benzoquinone (3).</p><p><b>CONCLUSION</b>The three compounds are new 1,4-benzoquinone derivatives.</p>

Determination of acetylharpagide in Ajuga decumbens by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a method of the quantitative determination of acetylharpagide in Ajuga decumbens.</p><p><b>METHOD</b>The chromatographic conditions were as follows: a Phenomenex Luna C18 column was used, the mobile phase was composed of acetontrile-water (15:85), the flow rate was 1.0 mL x min(-1) and the UV absorbance detection was set at 197 nm.</p><p><b>RESULT</b>Linearity of acetylharpagide was in the range of 0.6-3.6 microg (r = 0.9993), and the average recovery and RSD were 99.13% and 2.48%, respectively.</p><p><b>CONCLUSION</b>The contents of acetylharpagide ranged 0.40%-6.39% in A. decumbens. The method was simple, accurate and sensitive.</p>