Establishment of surfactant-associated protein a suicide gene system and analysis of its activity / 华中科技大学学报（医学）（英德文版）

Alveolar epithelial type II (AT II) cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells (fibroblasts). Progenitor cells are believed to possess capability of multi-potent transdifferentiation, which is closely related to the niche, suggesting the importance of establishment of a lung progenitor cell niche model. We hypothesized that pulmonary surfactant-associated protein A (SPA) suicide gene system would cause AT II cell to kill itself through apoptosis and leave its niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine kinase (rAAV-SPA-TK) system was established to get targeted apoptotic AT II cells. The apoptosis of AT II cells was detected by using MTT. The results showed that cloned SPA gene promoter had specific transcriptional activity in SPA high expression cells, and SPA high expression cells (H441) transfected with TK gene had higher sensitivity to ganciclovir (GCV) than SPA low expression cells (A549). In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system was observed by TUNEL. Finally, the successful packaging and application of rAAV-SPA-TK system provide experimental basis to get specific lung progenitor cell (AT II) niche in vitro and in vivo.

Establishment of surfactant-associated protein A suicide gene system and analysis of its activity / 华中科技大学学报（医学）（英德文版）

Alveolar epithelial type II (AT II) cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells (fibroblasts). Progenitor cells are believed to possess capability of multi-potent transdifferentiation, which is closely related to the niche, suggesting the importance of establishment of a lung progenitor cell niche model. We hypothesized that pulmonary surfactant-associated protein A (SPA) suicide gene system would cause AT II cell to kill itself through apoptosis and leave its niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine kinase (rAAV-SPA-TK) system was established to get targeted apoptotic AT II cells. The apoptosis of AT II cells was detected by using MTT. The results showed that cloned SPA gene promoter had specific transcriptional activity in SPA high expression cells, and SPA high expression cells (H441) transfected with TK gene had higher sensitivity to ganciclovir (GCV) than SPA low expression cells (A549). In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system was observed by TUNEL. Finally, the successful packaging and application of rAAV-SPA-TK system provide experimental basis to get specific lung progenitor cell (AT II) niche in vitro and in vivo.

Effect of dexamethasone on expression of AGR2 protein in asthmatic mice / 华中科技大学学报（医学）（英德文版）

This study examined the expression of the anterior gradient-2 (AGR2) protein and Muc5ac protein in the lung tissues of asthmatic mice and the effect of dexamethasone, with an attempt to explore the role of AGR2 in the over-secretion of mucus in the airway. Eighteen BALB/c mice were divided into asthma group, control group and dexamethasone group. In dexamethasone group, dexamethasone was intraperitoneally administered. Expression of AGR2 protein and Muc5ac protein in the murine lung tissues was immunohistochemically detected. IL-13 level was determined in the bronchoalveolar lavage fluid (BALF) by ELISA. The results exhibited that the expression of AGR2 protein in asthma group (0.522±0.041) was significantly higher than that in normal controls (0.361±0.047) (P<0.01) and bore a positive linear relationship to the expression of Muc5ac protein (r=0.873, P<0.05) and IL-13 level (r=0.828, P<0.05). Expression of AGR2 protein in the dexamethasone group (0.456±0.049) was significantly lower than that in the asthma group. It was concluded that: (1) the expression of AGR2 protein was significantly higher in asthmatic mice as compared with their normal counterparts; (2) the expression was obviously related to the expression of Muc5ac protein and IL-13; (3) dexamethasone could down-regulate the expression of AGR2 protein. Our findings suggested that AGR2 might be involved in the over-secretion of mucus in the airway in asthma.

Murine calcium-activated chloride channel family member 3 induces asthmatic airway inflammation independently of allergen exposure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Expression of murine calcium-activated chloride channel family member 3 (mCLCA3) has been reported to be increased in the airway epithelium of asthmatic mice challenged with ovalbumin (OVA). However, its role in asthmatic airway inflammation under no OVA exposure has not yet been clarified.</p><p><b>METHODS</b>mCLCA3 plasmids were transfected into the airways of normal BALB/c mice. mCLCA3 expression and airway inflammation in mouse lung tissue were evaluated. Cell differentials and cytokines in bronchoalveolar lavage fluid (BALF) were analyzed. The expression of mCLCA3 protein and mucus protein mucin-5 subtype AC (MUC5AC) were analyzed by Western blotting. The mRNA levels of mCLCA3, MUC5AC and interleukin-13 (IL-13) were determined quantitatively.</p><p><b>RESULTS</b>mCLCA3 expression was not detected in the control group while strong immunoreactivity was detected in the OVA and mCLCA3 plasmid groups, and was strictly localized to the airway epithelium. The numbers of inflammatory cells in lung tissue and BALF were increased in both mCLCA3 plasmid and OVA groups. The protein and mRNA levels of mCLCA3 and MUC5AC in the lung tissue were significantly increased in the mCLCA3 plasmid and OVA groups compared to the control group. The level of IL-13, but not IL-4, IL-5, IFN-γ, CCL2, CCL5 or CCL11, was significantly increased compared with control group in BALF in the mCLCA3 plasmid and OVA groups. The level of IL-13 in the BALF in the mCLCA3 plasmid group was much higher than that in the OVA group (P < 0.05). The level of mCLCA3 mRNA in lung tissue was positively correlated with the levels of MUC5AC mRNA in lung tissue, IL-13 mRNA in lung tissue, the number of eosinophils in BALF, and the content of IL-13 protein in BALF. The level of IL-13 mRNA in lung tissue was positively correlated with the number of eosinophils in BALF and the level of MUC5AC mRNA in lung tissue.</p><p><b>CONCLUSION</b>These findings suggest that increased expression of a single-gene, mCLCA3, could simulate an asthma attack, and its mechanism may involve mCLCA3 overexpression up-regulating IL-13 expression.</p>

Effect of dexamethasone on expression of AGR2 protein in asthmatic mice / 华中科技大学学报（医学）（英德文版）

This study examined the expression of the anterior gradient-2 (AGR2) protein and Muc5ac protein in the lung tissues of asthmatic mice and the effect of dexamethasone, with an attempt to explore the role of AGR2 in the over-secretion of mucus in the airway. Eighteen BALB/c mice were divided into asthma group, control group and dexamethasone group. In dexamethasone group, dexamethasone was intraperitoneally administered. Expression of AGR2 protein and Muc5ac protein in the murine lung tissues was immunohistochemically detected. IL-13 level was determined in the bronchoalveolar lavage fluid (BALF) by ELISA. The results exhibited that the expression of AGR2 protein in asthma group (0.522±0.041) was significantly higher than that in normal controls (0.361±0.047) (P<0.01) and bore a positive linear relationship to the expression of Muc5ac protein (r=0.873, P<0.05) and IL-13 level (r=0.828, P<0.05). Expression of AGR2 protein in the dexamethasone group (0.456±0.049) was significantly lower than that in the asthma group. It was concluded that: (1) the expression of AGR2 protein was significantly higher in asthmatic mice as compared with their normal counterparts; (2) the expression was obviously related to the expression of Muc5ac protein and IL-13; (3) dexamethasone could down-regulate the expression of AGR2 protein. Our findings suggested that AGR2 might be involved in the over-secretion of mucus in the airway in asthma.

Effects of bone marrow mesenchymal stem cells transplantation on the apoptosis of alveolar wall cells in papain and Co60-induced pulmonary emphysema rats / 中国应用生理学杂志

<p><b>AIM</b>To study the effects of bone marrow MSCs transplantation on the apoptosis of alveolar wall cells and the expression of Bcl-2 and Bax of lung tissue in papain and Co60-induced pulmonary emphysema rats.</p><p><b>METHODS</b>Female Lewis rats were randomly divided into three groups: control group, emphysema group, emphysema + MSCs transplantation group. Rats were sacrificed at days 14 and 28 after treatment. Morphologic analysis of the lung tissue was performed. The apoptosis of the lung cells was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of Bcl-2 and Bax were determined by immunohistochemical staining.</p><p><b>RESULTS</b>Emphysematous changes of the lung tissue were observed in emphysema group and emphysema + MSCs transplantation group. However, the emphysematous change in emphysema + MSCs transplantation group was improved compared with the emphysema group. There was significant difference in the number of alveolar counted per unit area (MAN), mean alveoli area (MAA) and mean linear interval(MLI) between emphysema group and emphysema + MSCs transplantation group. The apoptotic index of the alveolar wall cells in emphysema + MSCs transplantation group was less than that in the emphysema group. The percentage of Bcl-2 positive cells in emphysema + MSCs transplantation group was significantly higher than that in the emphysema group. The percentage of Bax positive cells in emphysema + MSCs transplantation group was significantly lower than that in the emphysema group. The ratio of Bcl-2/Bax of emphysema + MSCs transplantation group was significantly higher than that in the emphysema group.</p><p><b>CONCLUSION</b>Bone marrow MSCs transplantation inhibits the apoptosis of alveolar wall cells, upregulates the expression of Bcl-2 and downregulates the expression of Bax. This may be part of the reason that bone marrow MSCs transplantation improves the papain and Co60-induced pulmonary emphysema.</p>

Progress in Japanese herbal medicine in treatment of chronic kidney disease / 中国中药杂志

In Japan, Saireito and Onpi-to are widely used Japanese herbal medicine in the treatment of chronic kidney disease (CKD), which is a world-wide public health issue. In this review, it has been discussed the beneficial effects of Japanese herbal medicine, including Sairei-to and Onpi-to on multifarious renal damage in progression of CKD, such as mesangial lesion, inflammatory cell infiltration, cytokine expression, reactive oxygen species release, and aldosterone disorder, and then to clarify the mechanism of these herbs at molecular level by examining the effects on various injurious factors. Both Saireito and Onpi-to are effective agents for delaying the progression of CKD.

Altered surfactant protein A gene expression and protein homeostasis in rats with emphysematous changes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The decrease of surfactant protein (SP) secreted by the alveolar type II cell is one of the important causes of limiting air of pulmonary emphysema. However, the SP-A gene and protein changes in this disease are rarely studied. This study was undertaken to investigate alterations in SP-A gene activity and protein, and to explore their roles in the pathogenesis of emphysematous changes.</p><p><b>METHODS</b>Twenty Wistar rats were divided randomly into a normal control group (n = 10) and a cigarette smoking (CS) + lipopolysaccharide (LPS) group (n = 10). Ultra-structural changes were observed under an electron microscope. The number of cells positive for SP-A was measured by immunohistochemistry. The mRNA expression and protein level of SP-A in the lung tissues were determined by quantitative polymerase chain reaction (qPCR) and Western blot separately. The protein level of SP-A in lavage fluid was determined by Western blot.</p><p><b>RESULTS</b>The number of cells positive for SP-A of the CS + LPS group (0.35 +/- 0.03) was lower than that of the blank control group (0.72 +/- 0.06, P < 0.05). The level of SP-A in the lung tissues of rats in the CS + LPS group (0.2765 +/- 0.0890) was lower than that in the blank control group (0.6875 +/- 0.1578, P < 0.05). The level of SP-A in the lavage fluid of rats in the CS + LPS group (0.8567 +/- 0.1458) was lower than that in the blank control group (1.3541 +/- 0.2475, P < 0.05). The lung tissues of rats in the CS + LPS group showed an approximate increase (0.4-fold) in SP-A mRNA levels relative to beta-actin mRNA (P < 0.05).</p><p><b>CONCLUSIONS</b>The changes of SP-A may be related to emphysematous changes in the lung. And cigarette smoke and LPS alter lung SP-A gene activity and protein homeostasis.</p>

Effects of a combined regime of auricular-plaster and body acupuncture in treatment of cervical spondylosis of vertebral artery type / 中国针灸

<p><b>OBJECTIVE</b>To study effects of a combined regime of auricular-plaster and body acupuncture in treatment of cervical spondylosis of vertebral artery type and make a preliminary revelation of the mechanism.</p><p><b>METHODS</b>Ninety-two patients were randomly divided into 2 groups, the treatment group (n = 56) received the combined regime of auricular-plaster and body acupuncture, and the control group (n = 36) received treatment with body acupuncture. Clinical symptoms and signs, therapeutic effect and some indexes about vertebrobasilar hema-kinetics and hema-rheology were investigated before and after treatment.</p><p><b>RESULTS</b>The treatment group was better than the control group in the clinical overall effective rate (89.29%) and the clinically control rate (17. 85%), and in improving the following indexes, including dizziness and headache, the vertebrobasilar volume and rate of blood flow etab and IR (P < 0.05).</p><p><b>CONCLUSIONS</b>A combined regime of auricular-plaster and body acupuncture ameliorates not only main signs but also some indexes about vertebrobasilar hema-kinetics and hema-rheology. This treatment is an effective therapy for cervical spondylosis of vertebral artery type both in Malaysia and in China.</p>

Aldosterone/plasma renin activity ratio is a sensitive parameter for screening patients with primary aldosteronism / 中华心血管病杂志

<p><b>OBJECTIVE</b>To screen primary aldosteronism cases with ARR (aldosterone/plasma renin activity, ARR) from patients with hypertension, and to evaluate the diagnosis value of ARR in primary aldosteronism cases and analysis the clinical characters of primary aldosteronism cases.</p><p><b>METHODS</b>Nine hundred and two patients with hypertension were collected, the plasma aldosterone concentration to plasma renin activity ratio were detected by radio-immunity method, after that, ARR were calculated. Retrospective analysis was made of clinical data in 126 primary aldosteronism cases, which ARR were over 25.</p><p><b>RESULTS</b>One hundred and twenty-six cases (14%) were diagnosed as primary aldosteronism, and of them, 49 cases had hypokalemia. 25 patients received surgical operation and the rate of efficiency and cure of surgery treatment were 100% and 48%, respectively. The rate of efficiency and cure of drug treatment was 89% and 24% respectively.</p><p><b>CONCLUSIONS</b>Primary aldosteronism affects over 10% of patients with hypertension in China. Patients with hypertension and most patients with treatment-resistant hypertension should undergo screening for primary aldosteronism with ARR. A high ARR is a positive screening test result, a finding that warrants confirmatory testing.</p>

The role of glucocorticoid in treating cytomegalovirus pneumonia following renal transplantation / 中华器官移植杂志

Objective To study the role of glucocorticoid (GC) in treating patients with cyto- megalovirus (CMV) pneumonia following renal transplantation.Methods There were 75 cases CMV pneumonia following renal transplantation during one month (3 cases),2-6 months (64 cases) and more than 6 months (8 cases).All patients were subjected to the comprehensive treatments including anti-virus therapy.In 47 cases,GC was given (GC group),and in the rest 28 cases,GC was not administered (non-GC group).Results In GC group,40 cases (85.1%) were cured and there were 7 deaths (14.9%).In non-GC group,17 cases (60.7%) were cured and there were 11 deaths (39.3%).There was significant difference between two groups (P

Ciglitazone inhibits growth of lung cancer cells A549 in vitro and in vivo: an experimental study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the inhibitory effects of ciglitazone, a synthetic ligand of peroxisome proliferator-activated receptors (PPAR), on human lung cancer growth in vitro and in vivo and its mechanisms.</p><p><b>METHODS</b>Human lung cancer A549 cells cultured in vitro were treated with different concentrations of ciglitazone. The proliferative activity and cell cycle of A549 cells were determined by MTT assay and flow cytometry. Expression of PPARgamma protein was detected by Western blot. A549 cells (1 x 10(6) cells/nude mouse) were inoculated subcutaneously into nude mice, which were randomly divided into two groups, 10 in each: control group (group A) and ciglitazone treated group (group B). When the tumors grew to a size with diameter around 1 cm, ciglitazone 100 microl (100 micromol/L) was intratumorally injected every other day in group B mice. A total of 15 injections were given. Mice in group A were similarly treated with normal saline. One month later, tumors were excised and weighed. Expression of cyclin D1 and p21 protein were detected by immunohistochemistry and Western blot.</p><p><b>RESULTS</b>Growth of A549 cells was significantly inhibited in group B in a dose-dependent and time-dependent fashion as compared with that in group A. Most of the ciglitazone-treated cells arrested in G(1)/G(0) phase and the expression of PPARgamma protein was markedly up-regulated. The tumor weights in group A was (2.79 +/- 0.33) g and that in group B was (1.51 +/- 0.40) g, with an inhibition rate of 47.0%. The expression level of cyclin D1 in group A was significantly higher than that in group B, while the expression level of p21 protein in group A was significantly lower than that in group B.</p><p><b>CONCLUSION</b>Ciglitazone can effectively inhibit the growth of human lung cancer A549 and induce its differentiation by cell cycle arrest via PPARgamma activation.</p>