1.Recent advances in the study of AMPK and inflammatory pulmonary disease.
Acta Pharmaceutica Sinica 2014;49(8):1089-96
AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis. Recent studies demonstrated that AMPK is a novel signaling molecule modulating inflammatory responses and oxidative stress which are involved in inflammatory pulmonary diseases, such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary infectious diseases and pulmonary fibrosis. AMPK attenuates inflammatory lung injury by phosphorylating its downstream targets, such as sirtuin1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), p53 and forkhead box O3a (FoxO3a). This review summarized the relationship between AMPK and the development of inflammatory pulmonary diseases.
2.The synthesis and preliminary bioactivity of isoflavone derivatives
Hua HOU ; Lingling WENG ; Rong HU
Journal of Third Military Medical University 2003;0(13):-
Objective To synthesize soybean isoflavones, and their 7-alkaline analogues and to evaluate their uterotrophic activities and anti-uterotrophic activities preliminarily. Methods The target molecules were synthesized by multi-step from resorcinol and p-substituted phenylacetic acid as the starting material. Their uterotrophic activities and anti-uterotrophic activities were evaluated by female mouse at the concentration of 1.1?10 -2 ?mol/ml and 1.85?10 -3 ?mol/ml. Results Twenty-two compounds were synthesized, among which 4 intermediates and 12 isoflavones are new compounds. Conclusion All the target molecules except for 6a show weak uterotrophic activities and high anti-uterotrophic activities.
3.Effect of carbon monoxide releasing molecule on experimental periodontitis in rats.
Lingling WEI ; Meng HOU ; Ping WANG ; Hui SONG
West China Journal of Stomatology 2014;32(1):23-26
OBJECTIVETo evaluate the effects of carbon monoxide releasing molecule-2 (CORM-2) on experimental periodontitis in rats.
METHODSForty-two Wistar rats were divided into three groups. Rats in the normal group (NL group) did not undergo any procedure, whereas the other rats were ligatured and treated with saline solution (NaCl 0.9%) (LO group) or treated with CORM-2 (10 mg kg(-1) per day) (CO group). A 3-0 silk suture was placed around the mandibular first molars. Rats were sacrificed after 3, 7, and 10 d. Blood samples were collected from all animals for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) analysis. Changes in alveolar bone levels were measured clinically, and periodontal tissues were histopathologically examined to assess the infiltration of inflammatory cells.
RESULTSLigature placement increased alveolar bone loss and inflammatory cell infiltration in periodontal tissue. Alveolar bone loss in CO group was significantly higher than that in NL group, but was lower than that in LO group (P<0.05). The ratio of inflammatory cell infiltration in LO group was significantly higher than that in CO and NL groups, and that in CO group was lower than in LO group (P<0.05). Serum levels of TNF-alpha and IL-1beta in the LO group were significantly higher than those in the CO and NL groups, and those in CO group were lower than in LO group (P<0.05).
CONCLUSIONSystemic administration of CORM-2 reduced periodontal inflammation and alveolar bone loss in experimental periodontitis in rats.
Alveolar Bone Loss ; Animals ; Carbon Monoxide ; Periodontitis ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha
4.Effect of activation of Ca2+-permeable acid-sensing ion channel la on focal cerebral ischemia in diabetic rats
Jiajun CHEN ; Yumei HE ; Lingling HOU ; Chundi CHANG ; Ying XING
Chinese Journal of Geriatrics 2013;32(10):1106-1109
Objective To observe the expression of acid-sensing ion channel la (ASICla) and to investigate the effect of intracellular Ca2 + concentration on focal cerebral ischemia in diabetic rats.Methods 108 male Wistar rats were divided into three groups:group A [rats with middle cerebral artery occlusion (MCAO)],group B [rats with MCAO and diabetes (DM + MCAO)],group C [rats with MCAO and diabetes treated with fasudil intervention (DM+ MCAO+ fasudil)] (n=36 each).Samples were obtained at the time points of 1,3,6 and 24 h after ischemia respectively (n=9).Models of MCAO and DM+MCAO were prepared.Rats in DM+MCAO+Fasudil group were treated with fasudil 1 mg/Kg by caudal vein injection after half an hour when DM+MCAO model successfully prepared.ASICla expressions were detected at different time points of ischemia in the 3 groups respectively.Ca2+ concentration in ischemia cortex cells were determined at different time points of ischemia in group B and C.Results ASICla expressions were gradually increased along with the ischemia time in group A and B (group A:0.71±0.10,0.80±0.11,0.86±0.08,0.93±0.09;groupB:0.86±0.11,1.05±0.51,2.42±0.08,2.78±0.04; all P< 0.05),and ASICla expressions at different time points were higher in group B than in group A (all P< 0.05).Ca2-concentration were gradually increased along with the ischemia time in group B (106.32± 18.6,137.84±14.32,151.94± 18.38,183.61±7.96,all P<0.05).Compared with group B,the levels of ASICla expression and calcium current were reduced in group C.Conclusions The activation of ASICla increases calcium ion flow internal pathway leading to intracellular calcium overload,which may be one of the reasons for the aggravation of focal cerebral ischemia in diabetes.
5.Ultrastructural changes and significance of endometriotic rat model with HCG treatment
Lingling WU ; Yuzhu YIN ; Ke SUN ; Jinlang WU ; Hongying HOU
Chinese Journal of Pathophysiology 2015;(8):1516-1519
AIM:Toinvestigatewhetherandhowhumanchorionicgonadotropin(HCG)treatmentameliorates endometriosis in the endometriotic rat model .METHODS:The rat model of endometriosis was established and the model rats were divided into 4 groups.The rats in HCG groups were treated with 19.4, 25.8 and 51.6 IU/100 g of HCG every day (low-dose HCG, medium-dose HCG and high-dose HCG, respectively).The rats in control group were treated with 0.9%NaCl.After 15 days (3 estrous cycles), the ectopic lesion volume and ultrastructural characteristics in eutopic and ectopic endometria were investigated .RESULTS: After HCG treatment , the volume of endometriotic lesions was signifi-cantly smaller than that before treatment .Numerous and mitochondrial , endoplasmic reticulum and ribosomes were ob-served in the cytoplasm of eutopic and ectopic endometrium before treatment .After treatment , some cell structures were not clear , and mitochondrial cristae decreased or disappeared partly .Some cells were densed and shrinkage , autophagosome in cytoplasm increased , and mitochondria and endoplasmic reticulum swelt .CONCLUSION:HCG therapy appears to be an effective treatment for endometriosis in rats attributed to its influence on cell metabolism dysfunction of eutopic and ectopic endometria .
6.Expression of high mobility group box 1 in gingival tissues of chronic periodontitis.
Huaqiang ZHAO ; Pingping MU ; Lingling WEI ; Meng HOU ; Qinfeng SUN ; Hui SONG ; Pishan YANG
West China Journal of Stomatology 2013;31(2):191-194
OBJECTIVETo investigate the expression of high mobility group box 1 (HMGB1) in gingival tissues of chronic periodontitis.
METHODSHuman peripheral blood mononuclear cells(PBMC) were stimulated with 1 microg x mL(-1) lipopolysaccharide (LPS) for 24 h or 48 h. Expression and release of HMGB1 were checked by immunofluorescence and enzyme-linked immunosorbent assay (ELISA), respectively. PBMC were stimulated with 100 ng x mL(-1) HMGB1 or 50 ng x mL(-1) tumor necrosis factor-alpha (TNF-alpha), the expressions of TNF-alpha and HMGB1 in the supernatant were studied by ELISA. Gingival tissues and gingival crevicular fluids (GCF) were collected from patients and healthy people. Expression of HMGB1 in gingival tissues and GCF was studied using immunofluorescence and ELISA, respectively.
RESULTSHMGB1 was translocated from nucleus to cytosol in PBMC after LPS stimulation for 24 h. The content of HMGB1 in the supernatant from stimulated cells was significantly higher than that from unstimulated cells after 48 h (P < 0.01). HMGB1 was released by PBMC in response to TNF-alpha stimulation, it also stimulated PBMC to release TNF-alpha (P < 0.01). Translocation of HMGB1 from nucleus to cytosol was also found in infiltrated cells in gingival tissues from patients, and HMGB1 in GCF from patients was significantly higher than that from healthy people P < 0.01).
CONCLUSIONThe results suggest that HMGB1 may play an important role in the pathological progress of chronic periodontitis.
Chronic Periodontitis ; Gingiva ; HMGB1 Protein ; Humans ; Leukocytes, Mononuclear ; Male ; Tumor Necrosis Factor-alpha
7.Therapeutic effect of Qingzao Runfei Huazhuo Xingxue decoction on PM2.5-induced respiratory disease in ;mice
Jinbo ZHANG ; Li SUN ; Shiqing LI ; Lei ZHANG ; Yanxia CHEN ; Aihua HOU ; Yuejun MU ; Lingling DAI
Chinese Critical Care Medicine 2016;28(10):916-920
Objective To study the influence of Qingzao Runfei Huazhuo Xingxue decoction on pulmonary tissue and lung function in mouse model of lung injury induced by PM2.5, and to provide an idea of clinical prevention and treatment of respiratory diseases induced by PM2.5. Methods Totally 30 clean level male ICR mice were randomly divided into three groups: normal control group, model group and Qingzao Runfei Huazhuo Xingxue decoction intervention group, with 10 mice in each group. Model of PM2.5-induced respiratory disease in mice was reproduced by instilling nasal cavity drip PM2.5 suspension 40 mg/kg once a day for 6 weeks. In the treatment group, the mice were fed with the Qingzao Runfei Huazhuo Xingxue decoction twice a day from the 4th week of instilling PM2.5 suspension until the end of experiment. In the normal control group, the mice were fed as usual. At the end of the experiment, the total protein content in bronchoalveolar lavage fluid (BALF), and lung wet/dry weight (W/D) ratio was determined. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue under light microscope. The inflammatory mediators levels in lung tissue were determined by antibody-sandwich enzyme linked immunosorbent assay (ELISA). Results Respiratory system damage model was successfully reproduced by dripping of PM2.5 suspension in nasal cavity. Compared with normal control group, inflammatory changes and inflammatory cell infiltration in model group were significant, and lung W/D ratio (4.71±0.33 vs. 3.13±0.12), total protein content in BALF (mg/L: 363.98±18.24 vs. 82.13±12.78), tumor necrosis factor-α [TNF-α (ng/L): 185.72±0.23 vs. 31.03±0.16], interleukin-8 [IL-8 (ng/L): 531.85±37.83 vs. 72.64±16.72], and leukotriene B4 [LTB4 (ng/L): 931.74±48.64 vs. 483.81±41.74] in lung tissue were significantly increased (all P < 0.05). Compared with the model group, the inflammatory changes of lung tissue in Qingzao Runfei Huazhuo Xingxue decoction intervention group were significantly reduced, lung W/D ratio (3.92±0.41 vs. 4.71±0.33), total protein content in BALF (mg/L: 213.21±19.62 vs. 363.98±18.24), TNF-α (ng/L: 124.15±0.27 vs. 185.72±0.23), IL-8 (ng/L: 238.42±35.82 vs. 531.85±37.83) and LTB4 (ng/L: 582.85±31.00 vs. 931.74±48.64) levels in lung tissue in Qingzao Runfei Huazhuo Xingxue decoction intervention group were significantly decreased (all P < 0.05). Conclusion Qingzao Runfei Huazhuo Xingxue decoction can improve PM2.5-induced damage and pathological inflammatory changes in lung tissue, which provided some new ideas for the treatment of PM2.5-induced respiratory diseases.
8.Effect of WS070117M1 on chronic obstructive pulmonary disease in mice and the underling mechanisms of anti-inflammation.
Shuhua CAO ; Lingling XUAN ; Dongmei WANG ; Jianlin XIE ; Rentao JIANG ; Jinye BAI ; Song WU ; Qi HOU
Acta Pharmaceutica Sinica 2015;50(8):986-92
The aim of this study is to investigate the anti-inflammatory effect of the adenosine derivative N6-(3-hydroxylaniline) adenosine (WS070117M1) on cigarette smoke plus LPS (lipopolysaccharide)-induced chronic obstructive pulmonary disease (COPD) in mice and its mechanism. COPD model was established by exposing male BALB/c mice to cigarette smoke and challenged with LPS inhalation. Supernatants of bronchoalveolar lavage fluid (BALF) were harvested and IL-1β, IL-6, IL-8 and TGF-β1 levels were measured by ELISA (enzyme-linked immunesorbent assay). The number of total white blood cells and neutrophils in bronchoalveolar lavage fluid was counted separately. Lung tissue was stained with Mayer 's hematoxylin and eosin for histopathologic examination. pAMPKa protein expression and distribution of lung tissue were analyzed by immunohistochemistry method. In vitro, levels of AMPKα phosphorylation in phorbol-12- myristate-13-acetate (PMA) differentiated THP-1 cells was detected by immunohistochemistry, IL-8 level in supernatants of cigarette smoke condensate stimulating PMA differentiated THP-1 cells was measured by ELISA. The results showed that WS070117M1 treatment significantly activated AMPKa in the lung tissue. It also resulted in down regulation of IL-1β, IL-6, IL-8 and TGF-β1 levels in bronchoalveolar lavage fluid and IL-8 level in cigarette smoke condensate stimulating PMA differentiated THP-1 cells. In addition, WS070117M1 could inhibit the recruitment of total white blood cells and neutrophils. These results suggest that WS070117M1 may alleviate the airway inflammation by activating AMPK in the lung tissue.
9.Transrectal contrast enhanced ultrasound in distinguishing benign from malignant nodes of prostate
Yueqin ZHA ; Weidong SHEN ; Weiguo CHEN ; Heping LIN ; Lingling SHEN ; Zongqiang CAI ; Xiaofeng CAI ; Jianquan HOU
Chinese Journal of Medical Imaging Technology 2009;25(10):1867-1870
Objective To evaluate diagnostic value of transrectal gray scale contrast enhanced ultrasound (CEUS) in distinguishing benign from malignant nodes of prostate. Methods Thirty-three patients with 38 prostate nodes underwent real-time transrectal gray scale CEUS with SonoVue and contrast pulsed sequence (CPS). Contrast enhancement pattern of the prostate nodes were recorded and time-intensity curves (TIC) were drawn to calculate the parameters and difference between benign and malignant nodes. Results Twenty benign nodes (17 in inner gland) and 18 malignant ones (14 in external gland) were confirmed by pathology. Compared with normal peripheral zone, malignant lesions showed significantly earlier time to enhancement. The time to peak (TTP), accelerating time (ACT) and peak intensity (PI) of malignant lesions were lower than those of benign lesions (P<0.05).There was no significance in arrival time (AT) between the two groups (P>0.05). Conclusion Of all parameters in CEUS, TTP, ACT and PI are different between prostate benign and malignant lesions, and thus contribute to discriminate prostate cancer from benign diseases.
10.The value of contrast enhanced ultrasound in diagnosis of benign and malignant prostatic neoplasms
Yueqin ZHA ; Weidong SHEN ; Heping LIN ; Zongqiang CAI ; Weiguo CHEN ; Lingling SHEN ; Xiaofeng CAI ; Jianquan HOU
Chinese Journal of Ultrasonography 2010;19(1):32-35
Objective To evaluate the value of transrectal contrast enhanced ultrasound(TR-CEUS) in diagnosis of benign and malignant prostatic neoplasms.Methods Sixty patients with elevated level of serum prostate specific antigen and suspected prostate diseases were examined with transrectal uhrasound(TRUS), and TR-CEUS.The pattern and intensity of CEUS in these patients were observed;and the patients with nodules were examined with CEUS guided biopsy and sextant system biopsy after ultrasound imaging.Time-intensity curves (TIC) were drawn to calculate the parameters, and the difference between benign and malignant nodes was compared.Results All sixty prostate patients were confirmed by pathological examination.Thirty-seven patients belong to benign lesions, among them 15 patients with nodule lesion had total 20 nodules, while 22 cases had benign prostatic hyperplasia.In 23 cases of malignant lesions, 18 cases had centralized nodules and 5 cases showed diffuse pathologic changes.Benign nodes of inner gland showed a main pattern of homogenous enhancement and a clear node zone, whereas, malignant nodes displayed significant enhancement in peripheral tissue.The time to peak and accelerating time (ACT) of malignant nodes were shorter than those of benign nodes (P <0.05).There was no significance in arrival time (AT) between the two groups (P>0.05).The accordance rate of TR-CEUS in the differential diagnosis of benign and malignant prostatic lesions was higher than that of TRUS (P<0.05).In addition, the sensitivity, specificity and accurate rate of TR-CEUS were higher than those of TRUS, whereas, both misdiagnosis and missed diagnosis rate of TR-CEUS were lower than those of TRUS.Conclusions TR-CEUS has clinical value for early discovery of prostatic cancer and has higher application value to differentiate malignant from benign diseases.