Perceived participation and autonomy structural relationships among related factors in patients with stroke and hypertension in China: A ISM model approach.

Aims: To explore the structural relationship between perceived participation and autonomy among older adults with stroke and hypertension in home and community-based services (HCBSs) in the eastern coastal region of China. Design: An explorative cross-sectional study. Methods: From July to September 2021, a total of 714 respondents were reported to have stroke and hypertension, and their information was used in the analysis of this study. A multiple linear regression analysis was used to explore the factors influencing factors older adults' perceived participation and autonomy. Using the ISM model, we analyzed the factors affecting social participation in patients with stroke and hypertension and explained the logical relationships and hierarchy among the factors. Results: The mean score of perceived participation was 58.34 ± 27.57. Age, marital status, health insurance, living status, number of children, chronic diseases, sleep time, frequency of outings, and health utility value were significant factors affecting perceived participation and autonomy with stroke and hypertension patients. Among them, health insurance is the direct factor on the surface, age, number of children, chronic diseases, sleep time, frequency of outings, and health utility value are the intermediate indirect factors, and marital status and living status are the deep-rooted factors. Conclusion: By the study that the hierarchical structure provides a visualization of interrelationships and interdependences among the influencing factors of perceived participation and autonomy. It also may be a significant complement to traditional variable-entered approaches and construct an optimized multidimensional perspective of participation and autonomy. Future research should focus on optimizing the living environment of older adults with stroke and hypertension to explore the model of rehabilitative intervention and help patients successfully reintegrate into their families/societies.

Hypoxia induces endothelial­mesenchymal transition in pulmonary vascular remodeling.

It is well established that hypoxia induces epithelial­mesenchymal transition in vitro and in vivo. However, the role of hypoxia in endothelial­mesenchymal transition (EndMT), an important process in the pathogenesis of pulmonary hypertension, is not well­characterized. The present study demonstrated a significant downregulation of the endothelial marker CD31 and its co­localization with a mesenchymal marker, α­smooth muscle actin (α­SMA), in the intimal layer of small pulmonary arteries of rats exposed to chronic hypoxia. These results suggest a possible role of hypoxia in inducing EndMT in vivo. Consistent with these observations, pulmonary microvascular endothelial cells (PMVECs) cultured under hypoxic conditions exhibited a significant decrease in CD31 expression, alongside a marked increase in the expression of α­SMA and two other mesenchymal markers, collagen (Col) 1A1 and Col3A1. In addition, hypoxia promoted the proliferation and migration of α­SMA­expressing mesenchymal­like cells, but not of PMVECs. Of note, knockdown of hypoxia­inducible factor 1α (HIF­1α) effectively inhibited hypoxic induction of α­SMA, Col1A1 and the transcription factor Twist1, while rescuing hypoxic suppression of CD31; these results suggest that HIF­1α is essential for hypoxia­induced EndMT and that it serves as an upstream regulator of Twist1. Mechanistically, HIF­1α was identified to bind to the promoter of the Twist1 gene, thus activating Twist1 transcription and regulating EndMT. Collectively, the present results indicate that the HIF­1α/Twist1 pathway has a critical role in mediating the effect of hypoxia­induced EndMT in pulmonary arterial remodeling.

Automatic regulation of NF-κB by pHSP70/IκBαm to prevent acute lung injury in mice.

Controlling target gene expression is a vital step in the procedure of gene therapy upon acute lung injury (ALI). Excessive activation of nuclear factor-kappa B (NF-κB) has been the key point of the inflammation overwhelming process in onset of ALI. We designed and tested a variety of plasmid named pHSP70/IκBαm which conditionally carries a mutant inhibitor of kappa B (IκB) transgene to regulate the activity of NF-κB signaling pathway in its response to an inflammatory stimulus that causes acute lung injury. Results recorded along our experiments showed that pHSP70/IκBαm was able to control mutant IκB expression in RAW264.7 cells with reference to the level of inflammatory response induced by LPS, thereby inhibiting NF-κB activation and downstream inflammatory cytokine expression. Vivo experiments revealed that construction naming pHSP70/IκBαm reduced LPS-induced lung injury and the secretion of inflammatory factors from lungs, hearts, and livers of sample mice in a LPS dose-dependent manner. In conclusion, the promoter heat shocking protein 70(HSP70) regulatory sequence of the construction was shown to drive mutant IκB expression so that its levels were positively associated with the dose of LPS used to induce acute lung injury. NF-κB activation and the downstream expression of inflammatory factors were therefore down-regulated in along an efficient path and ameliorating the damage as a consequence of LPS-induced acute lung injury.

miR-29a-3p attenuates hypoxic pulmonary hypertension by inhibiting pulmonary adventitial fibroblast activation.

Activation of pulmonary adventitial fibroblasts plays a key role in the pulmonary vascular remodeling in hypoxic pulmonary hypertension. Previous studies showed that miRNAs participated in the regulation of fibroblast activation. This study explored the role of miR-29 in the activation of pulmonary adventitial fibroblasts and the therapeutic potential in hypoxic pulmonary hypertension. We found that hypoxia-induced pulmonary adventitial fibroblasts activation was accompanied with a drastic decrease of miR-29a-3p expression. Knockdown of hypoxia-inducible factor-1 α or Smad3 reversed the hypoxia-induced decrease of miR-29-3p in cultured pulmonary adventitial fibroblasts. In vitro, miR-29a-3p mimic inhibited the hypoxia-induced proliferation, migration, and secretion of pulmonary adventitial fibroblasts, suppressed the hypoxia-induced expression of α-smooth muscle actin and extracellular matrix collagen in pulmonary adventitial fibroblasts; however, miR-29a-3p inhibitor mimicked the effect of hypoxia on the activation of pulmonary adventitial fibroblasts. Further studies revealed that preventative or therapeutic administration of miR-29a-3p significantly decreased pulmonary artery pressure and right ventricle hypertrophy index and ameliorated pulmonary vascular remodeling in hypoxic pulmonary hypertension rats. These findings suggest that miR-29a-3p regulates the activation and phenotype of pulmonary adventitial fibroblasts in hypoxia and has preventative and therapeutic potential in hypoxic pulmonary hypertension.

Antitumor effects of artesunate on human breast carcinoma MCF-7 cells and IGF-IR expression in nude mice xenografts.

PURPOSE: The objective of this study was to investigate the anti-tumor effects and analyze the mechanism of artesunate (ART) action on breast cancer in vivo using tumor transplanted nude mice. METHODS: The human breast tumor cell line MCF-7 was transplanted into nude mice, and the animals were treated with various doses of ART alone or in combination with cyclophosphamide (CTX) or normal saline (NS). The tumor inhibitory effects were observed and compared, and the ultrastructural morphology of the transplanted tumor cells was observed by electron microscopy. The apoptosis rates and cell cycle status were detected by flow cytometry (FCM). The expression of apoptosis-related proteins p53, Bcl-2, Bax and Caspase-3 were detected by immunohistochemistry and IGF-IR was detected by western blot. The expression correlation for these proteins was also analyzed. RESULTS: The tumor inhibition rates in the low dose ART group, high dose ART group, CTX group and combined drug therapy group were (24.39±10.20)%, (40.24±7.02)%, (57.01±5.84)% and (68.29±5.1)%, respectively. The cell cycle was arrested in phase G0/G1 after treatment with ART. The expression of Bcl-2 was significantly reduced, and the expression levels of Bax and Caspase-3 were significantly increased in the ART group compared to the negative control saline group. There was no significant difference detected in p53 expression. The Bcl-2 level was negatively related to Bax and Caspase-3. The western blotting results showed IGF-IR downregulation. CONCLUSIONS: ART inhibits the growth of MCF-7 breast tumor cell xenografts in nude mice. The anti-tumor mechanism of ART for human breast carcinoma in nude mice might be correlated with the alteration of apoptosis related protein expression, which may further induce apoptosis and inhibit cell proliferation.

Leptin attenuates lipopolysaccharide or oleic acid-induced acute lung injury in mice.

Leptin is reported to be involved in acute lung injury (ALI). However, the role and underlying mechanisms of leptin in ALI remain unclear. The aim of this study was to determine whether leptin deficiency promoted the development of ALI. LPS or oleic acid (OA) were administered to wild-type and leptin deficient (ob/ob) mice to induce ALI. Leptin level, survival rate, and lung injury were examined. Results showed that leptin levels were predominantly increased in the lung, but also in the heart, liver, kidney, and adipose tissue after LPS adminiatration. Compared with wild-type mice, LPS- or OA-induced lung injury was worse and the survival rate was lower in ob/ob mice. Moreover, leptin deficiency promoted the release of proinflammatory cytokines. Exogenous administration of leptin reduced lethality in ob/ob mice and ameliorated lung injury partly through inhibiting the activation of NF-κB, p38, and ERK pathways. These results indicated that leptin deficiency contributed to the development of lung injury by enhancing inflammatory response, and a high level of leptin improved survival and protected against ALI.

Osthole improves acute lung injury in mice by up-regulating Nrf-2/thioredoxin 1.

Inhibiting reactive oxygen species (ROS) has been viewed as a therapeutic target for the treatment of acute lung injury (ALI). Osthole, an active component in Chinese herbal medicine, has drawn increasing attention because of its various pharmacological functions, including anti-inflammatory and anti-oxidative activities. The aim of the present study was to examine the effects of osthole on ALI induced by lipopolysaccharide (LPS) through intratracheal instillation. The mRNA and protein expression levels of thioredoxin 1 (Trx1) and the nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time PCR, reverse transcription PCR (RT-PCR) and Western blot, respectively. ROS production was measured by flow cytometry. Our results showed that osthole treatment improved the mice survival rates in the middle and high dosage groups, compared with the untreated LPS group. Moreover, osthole treatment significantly improved LPS-induced lung pathological damage, and it decreased the lung injury scores, lung wet/dry ratios and the total protein level in Bronchoalveolar lavage fluid (BALF). Osthole treatment dramatically reduced the H2O2, MDA and OH levels in the lung homogenates. LDH and ROS were markedly reduced in the osthole+LPS group in vitro. Furthermore, osthole increased Nrf2 and Trx1 expression in terms of mRNA and protein in vivo and in vitro. Nrf2 siRNA (siNrf2) could suppress the beneficial effects of osthole on ALI. In conclusion, the current study demonstrates that osthole exerted protective effects on LPS-induced ALI by up-regulating the Nrf-2/Trx-1 pathway.

Tanshinone IIA inhibits hypoxia-induced pulmonary artery smooth muscle cell proliferation via Akt/Skp2/p27-associated pathway.

We previously showed that tanshinone IIA ameliorated the hypoxia-induced pulmonary hypertension (HPH) partially by attenuating pulmonary artery remodeling. The hypoxia-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) is one of the major causes for pulmonary arterial remodeling, therefore the present study was performed to explore the effects and underlying mechanism of tanshinone IIA on the hypoxia-induced PASMCs proliferation. PASMCs were isolated from male Sprague-Dawley rats and cultured in normoxic (21%) or hypoxic (3%) condition. Cell proliferation was measured with 3 - (4, 5 - dimethylthiazal - 2 - yl) - 2, 5 - diphenyltetrazoliumbromide assay and cell counting. Cell cycle was measured with flow cytometry. The expression of of p27, Skp-2 and the phosphorylation of Akt were measured using western blot and/or RT-PCR respectively. The results showed that tanshinone IIA significantly inhibited the hypoxia-induced PASMCs proliferation in a concentration-dependent manner and arrested the cells in G1/G0-phase. Tanshinone IIA reversed the hypoxia-induced reduction of p27 protein, a cyclin-dependent kinase inhibitor, in PASMCs by slowing down its degradation. Knockdown of p27 with specific siRNA abolished the anti-proliferation of tanshinone IIA. Moreover, tanshinone IIA inhibited the hypoxia-induced increase of S-phase kinase-associated protein 2 (Skp2) and the phosphorylation of Akt, both of which are involved in the degradation of p27 protein. In vivo tanshinone IIA significantly upregulated the hypoxia-induced p27 protein reduction and downregulated the hypoxia-induced Skp2 increase in pulmonary arteries in HPH rats. Therefore, we propose that the inhibition of tanshinone IIA on hypoxia-induce PASMCs proliferation may be due to arresting the cells in G1/G0-phase by slowing down the hypoxia-induced degradation of p27 via Akt/Skp2-associated pathway. The novel information partially explained the anti-remodeling property of tanshinone IIA on pulmonary artery in HPH.

Osthole protects lipopolysaccharide-induced acute lung injury in mice by preventing down-regulation of angiotensin-converting enzyme 2.

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Angiotensin converting enzyme 2 (ACE2) plays a protective role in acute lung injury. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to have anti-inflammatory effect, but the effect of osthole on the ALI is largely unknown. The aim of this study is to explore whether and by what mechanisms osthole protects lipopolysaccharide(LPS)-induced acute lung injury. Herein, we found that osthole had a beneficial effect on LPS-induced ALI in mice. As revealed by survival study, pretreatment with high doses of osthole reduced the mortality of mice from ALI. Osthole pretreatment significantly improved LPS-induced lung pathological changes, reduced lung wet/dry weight ratios and total protein in BALF. Osthole also inhibited the release of inflammatory mediators TNF-α and IL-6. Meanwhile, osthole markedly prevented the loss of ACE2 and Ang1-7 in lung tissue of ALI mice. ACE2 inhibitor blocked the protective effect of osthole in NR 8383 cell lines. Taken together, our study showed that osthole improved survival rate and attenuated LPS-induced ALI and ACE2 may play a role in it.

Insulin reduces LPS-induced lethality and lung injury in rats.

Insulin is a main glucose homeostatic hormone in the body. Previous reports showed that insulin also exerted anti-inflammatory actions and attenuated systemic inflammatory response. Here, we observed the effects and the underlying mechanisms of insulin on lipopolysaccharide (LPS)-induced acute lung injury (ALI). As revealed by survival study, insulin reduced mortality of rats and prolonged their survival time. Meanwhile, insulin significantly reduced the levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1) in bronchoalveolar lavage fluid (BALF). Besides, insulin markedly inhibited the expression of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB). Taken together, these data provided information that insulin attenuated LPS-induced ALI may attribute partly to the inhibition of the production of cytokines, and the expression of TLR2, TLR4 and NF-κB.

Role of macrophage migration inhibitory factor in the proliferation of smooth muscle cell in pulmonary hypertension.

Pulmonary hypertension (PH) contributes to the mortality of patients with lung and heart diseases. However, the underlying mechanism has not been completely elucidated. Accumulating evidence suggests that inflammatory response may be involved in the pathogenesis of PH. Macrophage migration inhibitory factor (MIF) is a critical upstream inflammatory mediator which promotes a broad range of pathophysiological processes. The aim of the study was to investigate the role of MIF in the pulmonary vascular remodeling of hypoxia-induced PH. We found that MIF mRNA and protein expression was increased in the lung tissues from hypoxic pulmonary hypertensive rats. Intensive immunoreactivity for MIF was observed in smooth muscle cells of large pulmonary arteries (PAs), endothelial cells of small PAs, and inflammatory cells of hypoxic lungs. MIF participated in the hypoxia-induced PASMCs proliferation, and it could directly stimulate proliferation of these cells. MIF-induced enhanced growth of PASMCs was attenuated by MEK and JNK inhibitor. Besides, MIF antagonist ISO-1 suppressed the ERK1/2 and JNK phosphorylation induced by MIF. In conclusion, the current finding suggested that MIF may act on the proliferation of PASMCs through the activation of the ERK1/2 and JNK pathways, which contributes to hypoxic pulmonary hypertension.

Macrophage migration inhibitory factor contributes to hypoxic pulmonary vasoconstriction in rats.

BACKGROUND: Hypoxic pulmonary vasoconstriction may lead to pulmonary hypertension, but the underlying mechanisms of persistent vasoconstriction are still unclear. There is evidence that pulmonary inflammation contributes to the abnormalities of function in the pulmonary artery (PA) following chronic hypoxia exposure. Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine, and we found that expression of MIF was increased in the smooth muscle of PA from hypoxic pulmonary hypertensive rats. Therefore, the aim of the study was to investigate the role of MIF in modulating vasoreactivity of isolated PA rings. METHODS: Sprague-Dawley rats were challenged by intermittent chronic hypoxia exposure for 4 weeks to establish hypoxic pulmonary hypertension models. Subsequently, immunohistochemistry and western blot assay were used to examine the MIF expression in pulmonary artery. Moreover, isometric force displacement was measured in isolated intrapulmonary artery. RESULTS: In the isolated PA, our results showed that MIF mediated the enhanced pulmonary arterial vasoconstriction in response to chronic hypoxia, and the delayed hypoxic constriction in a biphasic pattern of constriction occurs in response to acute hypoxia. We also present the finding that MIF had no effect on force on its own, but concentration-dependently potentiated constrictions pre-evoked by phenylephrine under normoxic condition. The potentiation was independent of the endothelium. MIF-induced potentiation of phenylephrine-evoked constriction was partially inhibited by PKC inhibitor chelerythrine, p38 inhibitor SB 203580, ERK1/2 inhibitor U0126, respectively. CONCLUSIONS: Our results suggested that MIF enhanced vasoconstriction of pulmonary artery elicited by agonist through PKC, p38 and ERK1/2 signal pathways, which may contributes to hypoxic pulmonary vasoconstriction.

Antiinflammatory effects of matrine in LPS-induced acute lung injury in mice.

Matrine is one of the main active components of Chinese herb Sophora flavescens Ait (Kushen), which has been demonstrated to be effective in suppressing inflammation. The aim of the present study is to investigate the effect of matrine on LPS-induced lung injury. Lung injury was assessed by histological study and wet to dry weight ratios, as well as cell count and protein content in bronchoalveolar lavage fluid. We also detected MPO activity reflecting neutrophil infiltration and MDA activity examining oxidative stress in lung tissues. Cytokines and ROS production in cells were monitored by ELISA and flow cytometry, respectively. The results showed that high dose of matrine significantly reduced the mortality rate of mice with LPS administration. Treatment with matrine improved LPS-induced lung histopathologic changes, alleviated pulmonary edema and lung vascular leak, inhibited MPO and MDA activity,and reduced the production of inflammatory mediators including TNF-α, IL-6 and HMGB1. In vitro, matrine administration reduced the production of ROS and inflammatory factors, which was possibly associated with inhibition of NF-κB. In conclusion, the current study demonstrated that matrine exhibited a protective effect on LPS-induced acute lung injury by inhibiting of the inflammatory response, which may involve the suppression of ROS and tissue oxidative stress.

Tanshinone IIA attenuates seawater aspiration-induced lung injury by inhibiting macrophage migration inhibitory factor.

Inflammation takes responsibility for the seawater aspiration-induced lung injury. Tanshinone IIA (TIIA) can protect lipopolysaccharide-induced lung injury in mice through the inhibition of inflammation, but it is not reported whether TIIA have a protective effect on lung injury induced by seawater aspiration. Macrophage migration inhibitory factor (MIF) plays an important role in acute lung injury. In this study, we observed the effect of TIIA on the seawater aspiration-induced lung injury and the role of MIF in it. Seawater was aspirated into trachea of rats to make the lung injury model. TIIA was administered to investigate its beneficial effect on seawater-induced acute lung injury. The results showed that seawater aspiration led to hyoxemia, pulmonary edema, neutrophil infiltration, and lung histopathologic changes, with the elevated MIF expression in the lung tissues and plasma. However, these changes were attenuated by TIIA. In macrophage cells we also demonstrated that TIIA could inhibit MIF expression, nuclear factor κB (NF-κB) activity and release of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) induced by seawater. Besides, pretreatment with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid (ISO-1), the MIF antagonist, elevated NF-κB and cytokines induced by seawater were also reduced markedly. Furthermore, rMIF treatment alone increased the phosphorylation level of NF-κB and release of cytokines, which was almost abolished by TIIA. Taken together, our results suggested that TIIA exert a protective effect on the seawater aspiration-induced lung injury partly through downregulation of MIF and the subsequent NF-κB activity, as well as expression of IL-6 and TNF-α.

[Expression of platelet-derived growth factor receptor α and its ligand PDGF- A in breast cancer].

AIM: To investigate the potential significance of platelet-derived growth factor receptor-α (PDGFR-α) and platelet-derived growth factor A (PDGF-A) expression in mammary carcinomas, and analyze its correlation with the lymph node metastasis and the expression of PDGF-A. METHODS: Used immunohistochemistry to detect the protein expression of PDGFR-α and PDGF-A in paraffinembedded breast carcinomas. RESULTS: The expression of PDGFR-α and PDGF-A were observed in 51.7% and 61.7% in the breast carcinomas, respectively and showed an association with lymph node metastasis (P < 0. 05). A correlation was also found with the expression of PDGFR-α and PDGF-A (P<0.05). CONCLUSION: PDGFR-α is expressed in invasive breast carcinomas and is associated with biological aggressiveness.

Beta-estradiol attenuates hypoxic pulmonary hypertension by stabilizing the expression of p27kip1 in rats.

BACKGROUND: Pulmonary vascular structure remodeling (PVSR) is a hallmark of pulmonary hypertension. P27(kip1), one of critical cyclin-dependent kinase inhibitors, has been shown to mediate anti-proliferation effects on various vascular cells. Beta-estradiol (ß-E2) has numerous biological protective effects including attenuation of hypoxic pulmonary hypertension (HPH). In the present study, we employed ß-E2 to investigate the roles of p27(kip1) and its closely-related kinase (Skp-2) in the progression of PVSR and HPH. METHODS: Sprague-Dawley rats treated with or without ß-E2 were challenged by intermittent chronic hypoxia exposure for 4 weeks to establish hypoxic pulmonary hypertension models, which resemble moderate severity of hypoxia-induced PH in humans. Subsequently, hemodynamic and pulmonary pathomorphology data were gathered. Additionally, pulmonary artery smooth muscle cells (PASMCs) were cultured to determine the anti-proliferation effect of ß-E2 under hypoxia exposure. Western blotting or reverse transcriptional polymerase chain reaction (RT-PCR) were adopted to test p27(kip1), Skp-2 and Akt-P changes in rat lung tissue and cultured PASMCs. RESULTS: Chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of right ventricle/left ventricle plus septum (RV/LV+S) ratio, medial width of pulmonary arterioles, accompanied with decreased expression of p27(kip1) in rats. Whereas, ß-E2 treatment repressed the elevation of RVSP, RV/LV+S, attenuated the PVSR of pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of p27(kip1). Study also showed that ß-E2 application suppressed the proliferation of PASMCs and elevated the expression of p27(kip1) under hypoxia exposure. In addition, experiments both in vivo and in vitro consistently indicated an escalation of Skp-2 and phosphorylated Akt under hypoxia condition. Besides, all these changes were alleviated in the presence of ß-E2. CONCLUSIONS: Our results suggest that ß-E2 can effectively attenuate PVSR and HPH. The underlying mechanism may partially be through the increased p27(kip1) by inhibiting Skp-2 through Akt signal pathway. Therefore, targeting up-regulation of p27(kip1) or down-regulation of Skp-2 might provide new strategies for treatment of HPH.

Effects of sodium tanshinone II A sulphonate on hypoxic pulmonary hypertension in rats in vivo and on Kv2.1 expression in pulmonary artery smooth muscle cells in vitro.

AIM OF THE STUDY: To investigate the effect of sodium tanshinone IIA sulphonate (STS), a water-soluble derivative of tanshinone II A, on hypoxic pulmonary hypertension (HPH) in rats and its underlying mechanisms. MATERIALS AND METHODS: Rats were exposed to hypoxia for two or three weeks, pretreated with or without STS. We detected mean pulmonary arterial pressure (mPAP), the ratio of right ventricle weight to left ventricle with septum weight [RV/(LV+S)], wall thickness and voltage-activated potassium channel (Kv) 2.1 mRNA level of pulmonary arteries (PAs), respectively, and the in vitro effects of STS on proliferation and Kv2.1 expression of cultured pulmonary smooth muscle cells (PASMCs) from normal rats. Cell proliferation was determined by 3-(4,5-dimethylthiazal-2-yl)-2,5-diphenyltetrazoliumbromiede (MTT) assay and direct cell counting. Kv2.1 mRNA and protein level were evaluated by reverse transcription-polymerase chain reaction and Western blot, respectively. RESULTS: Chronic hypoxia increased values of mPAP and RV/(LV+S) and inhibited Kv2.1 mRNA level in PAs. Three weeks' daily STS pretreatment inhibited the hypoxia-induced increased mPAP and RV/(LV+S), pulmonary arterial thickening and up-regulated Kv2.1 mRNA level in PAs. Further study in vitro showed that STS suppressed significantly hypoxia-induced PASMCs proliferation and inhibition of Kv2.1 expression in PASMCs. CONCLUSIONS: STS might play protective effects on HPH through decreasing mPAP, V/(LV+S) and inhibiting structural remodeling in distal PAs. The mechanism of these effects may be attributed to inhibiting PASMCs proliferation and stimulating Kv2.1 expression.

Tanshinone IIA reduces lethality and acute lung injury in LPS-treated mice by inhibition of PLA2 activity.

Tanshinone IIA (TIIA) is one of the main active components from Chinese herb danshen. Previous reports showed that TIIA reduced the production of pro-inflammatory mediators stimulated with lipopolysaccharide (LPS). However, the effects of TIIA on LPS-induced acute lung injury are not fully understood. Here, we observed the effects of TIIA on mortality and lung injury in LPS-treated mice and on LPS-induced pulmonary epithelial cell injury, and further studied the underlying mechanism. As revealed by survival study, pretreatment with TIIA reduced mortality of mice and prolonged their survival time. Meanwhile, TIIA pretreatment significantly improved LPS-induced lung histopathologic changes, decreased lung wet-to-dry and lung-to-body weight ratios, inhibited lung myeloperoxidase activity and reduced protein leakage. TIIA also alleviated LPS-induced pulmonary epithelial cell injury, as proved by methyl thiazolyl tetrazolium (MTT) and lactic dehydrogenase assay. Furthermore, TIIA suppressed LPS-induced phospholipase A2 (PLA2) activity in both lung homogenate and bronchoalveolar lavage fluid. TIIA also inhibited the metabolites of PLA2, which was confirmed by results of thromboxane B2, prostaglandin E2 and leukotriene B4 detection. Besides, TIIA in vitro inhibited LPS-induced PLA2 activity in a dose-dependent manner. Western blotting showed that TIIA markedly inhibited the activation of nuclear factor kappa B (NF-kappaB) in LPS-treated mice. Taken together, these data firstly provided the novel information that the protective role of TIIA against LPS-induced lung injury may attribute partly to the inhibition of PLA2 activity and NF-kappaB activation.

[Study on the relative risk factors of adult measles in a case-control study in Qingdao city].

OBJECTIVE: To explore the relative risk factors of adult measles in Qingdao city. METHODS: Case-control study was used to collect the information from 70 adult measles cases and 140 controls. Information would include general social and demographic characteristics, history and times regarding measles vaccination, demography of the study of population etc. RESULTS: The case group had lower proportion of measles vaccination (chi2 = 26.88, P < 0.05, OR = 5.12, 95% CI: 2.69 - 9.73) than the control group with statistical significance. The vaccination frequencies were stratified as three ranks: 0, 1, > or = 2 times for analysis. When having 0 and 1 time measles vaccination, no statistical significance was found in these two groups (chi2 = 1.86, P = 0.173), but there were statistical significance between 0 and > or = 2 times (chi2 = 45.24, P = 0.000, OR = 13.35, 95% CI: 5.80 - 30.71), 1 and > or = 2 times (chi2 = 26.23, P = 0.000, OR = 7.91, 95% CI: 3.37 - 18.59) in the two groups. It was also found that the proportion of floating population was higher in case group than that of the control group (chi2 = 21.60, P < 0.01, OR = 4.06, 95% CI: 2.21 - 7.45). At the same time, statistically significant correlation was found between adult measles and average family incomes (chi2 = 2.23, P < 0.05, OR = 2.08, 95% CI: 1.15 - 3.76) by single-factor statistical analysis. CONCLUSION: Results showed that 'without history of measles vaccination' was key relative risk factor for the adult measles while being a part of 'floating population' and those having lower incomes were among vulnerable groups.

Effects of navelbine and docetaxel on gene expression in lung cancer cell strains.

AIM: To search genes sensitivity to the anti-cancer drugs navelbine (NVB) and docetaxel (DOC) in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell strains. METHODS: The sensitivity of 4 strains of SCLC and 6 strains of NSCLC to NVB and DOC was evaluated using the MTT assay. The expression of 1291 sensitive-related genes to the anti-cancer drugs in 10 lung cancer cell strains was measured using cDNA macroarrays and the relationship was analyzed. RESULTS: In total, there were 56 (r > or = 0.4) genes sensitive to NVB and DOC. For NVB: 36 genes were sensitive to NVB, 20 co-expressed genes between the SCLC+NSCLC set and the NSCLC set; 27 expressed genes and 7 specially expressed genes in the SCLC+NSCLC set; and 29 expressed genes and 9 specially expressed genes in the NSCLC set. For DOC, 50 genes were sensitive to DOC, 12 co-expressed genes between the SCLC+NSCLC set and the NSCLC set; 24 expressed genes and 12 specially expressed genes in the SCLC+NSCLC set; and 38 expressed genes and 26 specially expressed genes in the NSCLC set. The genes sensitive to NVB and DOC in lung-cancer cell stains were mainly divided into the following 4 categories: signal transduction molecules, cell factors, transcription factors and metabolism-related enzymes and inhibitors. CONCLUSIONS: There were obvious differences in genes related to NVB and DOC between SCLC and NSCLC cell strains, but the same as categories of function.