[Health Risk Assessment for an Arsenic-contaminated Site Based on Monte Carlo Simulation and Parameters Optimization].

Risk assessment is a critical part of risk management for contaminated sites. However， in the specific management practice of As-contaminated sites， it is difficult to obtain realistic health risks for contaminated sites based on the total amount of pollutants and determined values of the model， thus preventing the control requirements of later remediation to be met. An increasing number of studies have recently been conducting risk assessments by considering bioavailability， modification parameters， and combined probabilistic models. To improve the accuracy of risk assessment results， taking a large As-contaminated site as a case， 432 sampling sites were set up and collected at different depths to analyze the level and distribution characteristics of As pollution， and probabilistic risk assessment was conducted with the modification of model parameters through literature research and Monte Carlo simulation. Then， the impact of traditional methods and probabilistic methods on health risk assessment was explored in comparison. The results indicated that ω（As） in the top soil of the study area ranged from 2.70-97.0 mg·kg-1， with a spatial variation coefficient of 0.61 and weaker spatial continuity. The carcinogenic risk and hazard index obtained by the traditional risk assessment method were 2.12E-4 and 8.36， respectively， which obviously overestimated the actual risk level and were not conductive to the refined management of As-contaminated sites. Combined with modification of model parameters and probabilistic risk assessment， the non-carcinogenic risk for adults and children was found to be at an acceptable level， and the carcinogenic risk was reduced by nearly an order of magnitude compared to that in the conventional method. Considering the relative biological effectiveness （RBA） of As， the 95% quantile of the total carcinogenic risk was 1.24E-5， a reduction of up to 36.41% compared to the uncorrected corresponding risk value of 1.95E-5. The carcinogenic risk of soil As for adults and children in the study area exceeded acceptable risk levels 1E-6， with oral ingestion of soil being the primary route of exposure. In addition， the results of the sensitivity analysis of the parameters showed that As concentration， daily oral ingestion rate of soils， and exposure duration of children had relatively larger effects for health risks. This work will provide a methodological and theoretical basis for achieving accurate risk assessment of As-contaminated sites and provide concepts for refined risk management.

Mesenchymal stem cell therapy in pulmonary fibrosis: a meta-analysis of preclinical studies.

BACKGROUND: Pulmonary fibrosis (PF) is a devastating disease characterized by remodeling of lung architecture and abnormal deposition of fibroblasts in parenchymal tissue and ultimately results in respiratory failure and death. Preclinical studies suggest that mesenchymal stem cell (MSC) administration may be a safe and promising option in treating PF. The objective of our meta-analysis is to assess the efficacy of MSC therapy in preclinical models of PF. METHODS: We performed a comprehensive literature search in PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to March 17, 2021. Studies that assessed the efficacy of MSC therapy to animals with PF were included. The SYRCLE bias risk tool was employed to evaluate the bias of included studies. The primary outcomes included survival rate and pulmonary fibrosis scores. Meta-analysis was conducted via Cochrane Collaboration Review Manager (version 5.4) and Stata 14.0 statistical software. RESULTS: A total of 1120 articles were reviewed, of which 24 articles met inclusion criteria. Of these, 12 studies evaluated the survival rate and 20 studies evaluated pulmonary fibrosis scores. Compared to the control group, MSC therapy was associated with an improvement in survival rate (odds ratios (OR) 3.10, 95% confidence interval (CI) 2.06 to 4.67, P < 0.001, I2 = 0%) and a significant reduction in pulmonary fibrosis scores (weighted mean difference (WMD) 2.05, 95% CI -2.58 to -1.51, P < 0.001, I2 = 90%). CONCLUSIONS: MSC therapy is a safe and effective method that can significantly improve the survival and pulmonary fibrosis of PF animals. These results provide an important basis for future translational clinical studies.

Dihydroartemisinin Inhibits the Proliferation, Colony Formation and Induces Ferroptosis of Lung Cancer Cells by Inhibiting PRIM2/SLC7A11 Axis.

OBJECTIVE: Lung cancer is the first leading cause of cancer-related deaths both worldwide and in China and threatens human health and quality of life. New drugs and therapeutic methods are urgently needed. Our study evaluated the roles of dihydroartemisinin (DHA) in lung cancer and further explored its underlying mechanisms. METHODS: CCK-8, colony formation and trypan blue exclusion assays were used to detect the cell viability, colony formation ability and cell death. qRT-PCR and Western blotting assays were applied to analyze the expressions of key molecules. RESULTS: DHA inhibited the proliferation and colony formation abilities and enhanced the cell death and induced ferroptosis of lung NCI-H23 and XWLC-05 cancer cells. DHA reduced PRIM2 expression and silencing PRIM2 mimicked the inhibitory roles on proliferation and colony formation and promotive roles on cell death and ferroptosis of DHA in lung NCI-H23 and XWLC-05 cancer cells. We further found that DHA treatment and loss of PRIM2 reduced the GSH level and increased the cellular lipid ROS and mitochondrial MDA levels, and further downregulated the expressions of SLC7A11 and ß-catenin in lung cancer cells, respectively. Exogenetic overexpression of PRIM2 recovered the inhibitory effects of DHA on proliferation and colony formation in lung NCI-H23 cancer cells, meanwhile loss of PRIM2 sensitizes NCI-H23 cells to DHA therapy. In vivo experiment further showed that DHA treatment significantly suppressed the tumor growth and downregulated PRIM2 and SLC7A11. CONCLUSION: Our study suggested that DHA inhibited the proliferation, colony formation and enhanced cell death and induced ferroptosis of lung cancer cells by inactivating PRIM2/SLC7A11 axis. Loss of PRIM2 induced ferroptosis might developed to be a novel therapeutic method in lung cancer therapy.

[Exposure Levels, Sources, and Health Risks of Heavy Metal Components of PM2.5 in Housewives in Rural Shanghai].

To investigate exposure characteristics and potential health risk of PM2.5-bound heavy metals in housewives in rural areas, 265 personal exposure samples from 143 subjects were collected in the Songjiang district, Shanghai from February 2017 to June 2018. Mass concentrations of 13 elements in PM2.5 were determined by energy-dispersive X-ray fluorescence spectrometry (ED-XRF). The sources of heavy metal components in PM2.5 were analyzed using positive matrix factorization (PMF). The inhalation health risks of exposure to Ni, V, Cr, Mn, As, and Pb were analyzed using the US EPA health risk assessment model. The results showed that the average concentration of personal exposure to PM2.5 was 40.61 µg·m-3 in housewives, which was higher than the concentration at peripheral monitoring stations. The carcinogenic risks of Cr(Ⅵ)and As exceeded the acceptable risk level (10-6). The non-carcinogenic risks of V, Cr(Ⅵ), Mn, Ni, and As were all below the safety threshold, while the total non-carcinogenic risks of these five elements were higher than the safety threshold (>1). The results of PMF indicated that resuspended dust and indoor dust(43.8%), the metallurgy industry(34.6%), coal combustion(14.5%), and fossil-fuel combustion(7.2%)were the major sources of ten elements (Al, Ti, V, Cr, Mn, Fe, Ni, Zn, As, and Pb) in PM2.5. Based on the results of health risk assessment of pollution sources, control measures on the metallurgy industry and fossil-fuel combustion should be further strengthened.

Knockdown of TNF­α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL­10 expression.

Intestinal ischemia and reperfusion (II/R) injury often triggers severe injury in remote organs, with the lungs being considered the main target. Excessive elevation of proinflammatory cytokines is a major contributor in the occurrence and development of II/R­induced acute lung injury (ALI). Therefore, the present study aimed to investigate whether blocking tumor necrosis factor­α (TNF­α) expression could protect the lungs from injury following II/R, and to explore the possible underlying mechanism involving interleukin­10 (IL­10). Briefly, II/R was induced in rats by 40 min occlusion of the superior mesenteric artery and celiac artery, followed by 8, 16 or 24 h of reperfusion. Subsequently, lentiviral vectors containing TNF­α short hairpin (sh)RNA were injected into the right lung tissues, in order to induce TNF­α knockdown. The severity of ALI was determined according to lung injury scores and lung edema (lung wet/dry weight ratio). The expression levels of TNF­α were analyzed by quantitative polymerase chain reaction (qPCR), western blotting and immunofluorescence (IF) staining. IL­10 expression, in response to TNF­α knockdown, was detected in lung tissues by qPCR and IF. The results detected marked inflammatory responses, and increased levels of lung wet/dry weight ratio and TNF­α expression, in the lungs of II/R rats. Conversely, treatment with TNF­α shRNA significantly alleviated the severity of ALI and upregulated the expression levels of IL­10 in lung tissues. These findings suggested that TNF­α RNA interference may exert a protective effect on II/R­induced ALI via the upregulation of IL­10. Therefore, TNF­α knockdown may be considered a potential strategy for the prevention or treatment of ALI induced by II/R in future clinical trials.

Effect of Mono-2-ethyhexyl Phthalate on DNA Methylation in Human Prostate Cancer LNCaP Cells.

OBJECTIVE: To evaluate whether mono (2-ethylhexyl) phthalate (MEHP) affects genomic DNA methylation and the methylation status of some specific genes such as patched gene (PTCH) and smoothened gene (SMO) in LNCaP cells. METHODS: LNCaP cells were treated with MEHP (0, 1, 5, 10, and 25 µmol/L) for 3 days. An ELISA assay was preformed to detect genomic methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) content. A pyrosequencing assay was applied to assess DNA methylation in PTCH and SMO gene promoters. The correlation between DNA methylation and gene expression was assessed. RESULTS: The proportion of cytosines with 5-mC methylation in LNCaP cells was significantly decreased by MEHP (1, 5, 10, and 25 µmol/L) in a dose-dependent manner (P < 0.01). For genes in the Hedgehog pathway, there was no significant MEHP concentration-dependent difference in the DNA methylation of PTCH and SMO. CONCLUSION: MEHP might affect the progression of prostate cancer through its effect on global DNA methylation.

Interleukin­6 RNA knockdown ameliorates acute lung injury induced by intestinal ischemia reperfusion in rats by upregulating interleukin­10 expression.

Acute lung injury (ALI) is a common complication following intestinal ischemia/reperfusion (II/R) injury and contributes to the associated high mortality rate. However, the underlying mechanism is poorly understood and treatments are limited. RNA interference (RNAi) has been demonstrated to provide a promising disease treatment strategy both in vitro and in vivo. Therefore, the present study aimed to test whether blocking the proinflammatory cytokine IL­6 by RNAi may protect the lungs from remote organ injury following II/R, and to investigate the potential underlying mechanisms. A total of 176 adult healthy male Sprague­Dawley rats were randomly divided into sham, II/R, negative­control and IL­6­short hairpin (sh)RNA groups. The rats underwent II/R injury with occlusion of the superior mesenteric artery and coeliac artery to induce ischemia for 40 min, and were subsequently reperfused for 0­48 h. The negative­control group received a control lentiviral vector containing scrambled or non­specific sequences, and the IL­6­shRNA groups were administered with a vector containing an IL­6 shRNA sequence to affect RNAi­mediated knockdown of IL­6. ALI severity was determined by lung edema (lung wet/dry ratio) and histological analysis (lung injury scores). IL­6 localization, and mRNA and protein expression levels, were detected by immunofluorescence, reverse transcription­quantitative polymerase chain reaction and western blot analysis, respectively. IL­10 expression induced by IL­6 knockdown in lung tissues was additionally detected. IL­6 RNAi was revealed to significantly reduce the expression of IL­6, which was associated with upregulated IL­10 expression in lung tissues. Consequently, the severities of ALI and edema induced by II/R were substantially improved. In conclusion, the present study demonstrated that IL­6 RNAi may protect the lung from ALI induced by II/R, and that this protective role may be associated with upregulation of IL­10. These findings may contribute to the development of an IL­6­RNAi­based therapeutic strategy for the treatment of II/R­induced ALI.

Surveillance for respiratory infectious diseases caused by 6 common viruses in a recruit training site in the Northern region of China.

BACKGROUND: Recruit training sites are places with a high incidence of respiratory infectious diseases. Effective surveillance for acute respiratory infectious diseases in a recruit training site is an important way to prevent disease outbreaks. METHODS: Eight hundred recruits (722 males and 78 females) enlisted in autumn 2015 received a background survey within 24 h of settlement at the recruit training site, including their general personal information, vaccination history, mental status and clinical symptoms. Then, nasopharyngeal swabs of these recruits were collected to detect common respiratory pathogens [influenza virus type A, influenza virus type B, adenovirus (Adv), human respiratory syncytial virus, human bocavirus and human metapneumovirus] by PCR. In addition, fasting venous blood was collected in the morning for adenovirus IgG antibody detection. During the three months of training, the recruits were monitored for symptoms of respiratory infection, and nasopharyngeal swabs were collected from those with an axillary temperature ≥38 °C and other respiratory symptoms within 4 h of symptom onset. Samples were further examined by PCR. RESULTS: Among the 795 effective nasopharyngeal swab samples collected during survey, two cases of group C type 1 adenovirus were identified by PCR. During the 3 months of training, fever and respiratory symptoms occurred in 39 recruits (incidence rate of 4.9%) and 5 cases of adenovirus were detected (positive rate of 12.8%). Genotyping showed 3 cases of type 4 adenovirus and 2 of type 3 adenovirus. No type 7, 14 or 55 adenovirus was detected. The Adv-IgG positive rate of recruits was 48.2%. Among the 5 Adv positive cases with fever and respiratory symptoms, 4 were Adv-IgG positive. CONCLUSION: The pathogen carrier rate in recruits was low, and only group C adenovirus, which causes mild infection in humans, was detected. No respiratory outbreak was observed at the recruit training site, and sporadic cases were mainly caused by type 3 and type 4 adenoviruses.

The PI3K-AKT-mTOR pathway activates recovery from general anesthesia.

We investigated roles of PI3K-AKT-mTOR pathway in recovery from general anesthesia. Sprague-Dawley rats divided into five groups: saline+artificial cerebrospinal fluid (ACSF; Group A), ketamine+ACSF (Group B), ketamine+IGF-1 (Group C), ketamine+PI3K inhibitor (Group D), and PI3K/Akt agonists (Group E). Proportion of δ waves on ECoGs was recorded. Rats were tested for duration of loss of righting reflex (LORR), ataxic period and behavior in Morris water maze. mRNA and protein expression of members of PI3K-AKT-mTOR pathway were measured by RT-qPCR and Western blots. Histopathologic changes in hippocampal tissues observed by HE staining. We found that the proportion of δ waves decreased in Group C, while increased in Group D compared with Group B; the durations of LORR and ataxic period were shorter in Group C, but longer in Group D. In Morris water maze, escape latency (EL) and duration and frequency of staying on platform was shorter in Group C and longer in Group D than in Group B. Group A exhibited low expression of proteins in PI3K-AKT-mTOR pathway, while p-AKT, p-mTOR and p-P70S6K expression increased in cerebral cortex, brain stem, and thalamus in Group C. By contrast, expression of those proteins was lower in Group D than Group B. Those proteins expressions were higher in Group E than in Group A. HE staining showed that anesthesia may induce cell apoptosis in rat hippocampal CA1 areas, and PI3K/Akt agonists could inhibit apoptosis. Our results suggest that activation of PI3K-AKT-mTOR pathway may promote recovery from general anesthesia and enhance spatial learning and memory.

Maternal Disononyl Phthalate Exposure Activates Allergic Airway Inflammation via Stimulating the Phosphoinositide 3-kinase/Akt Pathway in Rat Pups.

OBJECTIVE: To evaluate the effect of diisononyl phthalate (DINP) exposure during gestation and lacta- tion on allergic response in pups and to explore the role of phosphoinositide 3-kinase/Akt pathway on it. METHODS: Female Wistar rats were treated with DINP at different dosages (0, 5, 50, and 500 mg/kg of body weight per day). The pups were sensitized and challenged by ovalbumin (OVA). The airway response was assessed; the airway histological studies were performed by hematoxylin and eosin (HE) staining; and the relative cytokines in phosphoinositide 3-kinase (PI3K)/Akt pathway were measured by enzyme-linked immunosorbent assay (ELISA) and western blot analysis. RESULTS: There was no significant difference in DINP's effect on airway hyperresponsiveness (AHR) between male pups and female pups. In the 50 mg/(kg·d) DINP-treated group, airway response to OVA significantly increased and pups showed dramatically enhanced pulmonary resistance (RI) compared with those from controls (P<0.05). Enhanced Akt phosphorylation and NF-κB translocation, and Th2 cytokines expression were observed in pups of 50 mg/(kg·d) DINP-treated group. However, in the 5 and 500 mg/(kg·d) DINP-treated pups, no significant effects were observed. CONCLUSION: There was an adjuvant effect of DINP on allergic airway inflammation in pups. Maternal DINP exposure could promote OVA-induced allergic airway response in pups in part by upregulation of PI3K/Akt pathway.

Prenatal phthalate exposure, infant growth, and global DNA methylation of human placenta.

Prenatal phthalate exposure has been shown to be associated with reduced fetal growth. Epigenetic changes such as DNA methylation might be a molecular mechanism through which phthalate exposure affects fetal growth. In this study, we examined associations between prenatal phthalate exposure, infant growth, and global DNA methylation in human placenta samples. We measured global DNA methylation of 119 subjects [55 fetal growth restriction (FGR) cases and 64 normal controls], as assessed by long interspersed nuclear element-1 (LINE-1) methylation, via quantitative polymerase chain reaction-pyrosequencing. Prenatal phthalate exposure was assessed by measuring maternal urinary phthalate metabolites concentrations using high-performance liquid chromatography-tandem mass spectrometry. Concentrations of mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and SumDEHP (molar sum of MEHP, MEHHP, and MEOHP) were significantly higher in FGR cases than those in normal controls (P = 0.002, 0.003, and 0.002, respectively). Placental LINE-1 methylation were found to be positively associated with fetal birth weight standard deviation scores, and negatively associated with urinary phthalate metabolites concentrations (MEHHP and SumDEHP). Every natural-log unit increase in urinary concentrations of MEHHP and SumDEHP was associated with 0.015 (ß = -0.015, P = 0.150) and 0.012 kg (ß = -0.012, P = 0.167) decrease in birth weight mediated through LINE-1 methylation. These findings suggest that changes in placental LINE-1 methylation might be part of the underlying biological pathway between prenatal phthalate exposure and adverse fetal growth.

Cross-sectional study of the relationship of peripheral blood cell profiles with severity of infection by adenovirus type 55.

BACKGROUND: The immunologic profiles of patients with human adenovirus serotype 55 (HAdV-55) infections were characterized in subjects diagnosed with silent infections (n = 30), minor infections (n = 27), severe infections (n = 34), and healthy controls (n = 30) during a recent outbreak among Chinese military trainees. METHODS: Blood was sampled at the disease peak and four weeks later, and samples were analyzed to measure changes in leukocyte and platelet profiles in patients with different severities of disease. Differential lymphocyte subsets and cytokine profiles were measured by flow cytometry and Luminex xMAP®, and serum antibodies were analyzed by ELISA and immunofluorescence staining. RESULTS: Patients with severe HAdV infections had higher proportions of neutrophils and reduced levels of lymphocytes (p < 0.005 for both). Patients with minor and severe infections had significantly lower platelet counts (p < 0.005 for both) than those with silent infections. The silent and minor infection groups had higher levels of dendritic cells than the severe infection group. Relative to patients with silent infections, patients with severe infections had significantly higher levels of IL-17+CD4+ cells, decreased levels of IL-17+CD8+ cells, and higher levels of IFN-γ, IL-4, IL-10, and IFN-α2 (p < 0.001 for all comparisons). CONCLUSIONS: Patients with different severities of disease due to HAdV-55 infection had significantly different immune responses. These data provide an initial step toward the identification of patients at risk for more severe disease and the development of treatments against HAdV-55 infection.

Reversal of bone cancer pain by HSV-1-mediated silencing of CNTF in an afferent area of the spinal cord associated with AKT-ERK signal inhibition.

Pain induced by bone metastases has a strong impact on the quality of life of patients with cancer, but current therapies for bone cancer pain cannot attain a satisfactory therapeutic goal because of various adverse reactions. Currently, advanced monitoring is required to clarify pathogenic mechanisms, so as to develop more effective treatments. We constructed herpes simplex virus carrying small interference RNA for CNTF (HSV-siCNTF) and established cancer-induced bone cancer pain models with intra-tibial injection of MRMT-1 cells. At different time points after treatment, sensory function indicated by thermal hyperalgesia and mechanical allodynia was measured. The mechanism underlying sensory function regulated by CNTF was also determined. There was apparent mechanical and thermal hyperalgesia in rats injected with bone cancer cells. Bone destruction was detected in the area of tibia injected with tumor cells by the plain radiography. MRMT-1 cells and the increased number of osteoclasts were found in tibia sections stained with hematoxylin and eosin. Intrathecal injection of morphine or HSV-siCNTF significantly reduced the mechanical allodynia and thermal hyperalgesia, which was accompanied by astrocyte hypertrophy. The number of nerve fibers positive for substance P (SP) and calcitonin gene related peptide (CGRP) was significantly decreased, which was consistent with the decrease of CNTF, ERK/pERK, AKT/pAKT and c-fos expression. These results demonstrate that the HSV-siCNTF gene therapy appears beneficial for the treatment of pain induced by bone cancer via blocking the AKT-ERK signaling pathway. Our data suggest that CNTF interference may be considered a new target to develop an effective management for bone cancer pain.

Oxysophoridine suppresses the growth of hepatocellular carcinoma in mice: in vivo and cDNA microarray studies.

OBJECTIVE: To observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms. METHODS: C57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously, then divided into 5 groups (14 per group), and treated with oxysophoridine (50, 100, or 150 mg/kg) or cisplatin (4 mg/kg) for 10 days. Inhibitory rate of tumor, body weight gain, and influence indices on internal organs (liver, spleen and thymus) were evaluated. The differentially expressed genes between the oxysophoridine-treated group, and the control group were analyzed using cDNA microarray and quantitative real-time PCR (qRT-PCR) experiments. RESULTS: Compared with the tumor weight of the control group (2.75±0.66 g), oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice (P <0.01), with 0.82±0.36 g, 0.57±0.22 g, and 1.22±0.67 g for the tumor weight in the low, moderate, and high dose treatment group, respectively. The moderate dose led to the highest inhibitory rate, 79.3%. Observation of body weight gain and influence on three organs showed that compared with cisplatin, oxysophoridine produced fewer side effects in vivo. cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis, with the Tnfrsf11b (osteoprotegerin) gene being the most significantly affected. CONCLUSION: Oxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma, and its anti-hepatoma effect was probably related to osteoprotegerin activation.

[Expression of trkB gene in the pulmonary tissue of rats with lung injury induced by cerebral ischemia].

OBJECTIVE: To investigate the expression of tyrosine kinase B (trkB) in lung tissue of rats with lung injury induced by brain ischemia. METHODS: Twenty six adult SD rats were divided into sham group and brain ischemia lung injury (BILI) group. All rats were sacrificed at 3 days after the operation of modeling, lung tissues were then harvested to measure the protein and mRNA level of trkB by the methods of western blot and RT-PCR, the location of trkB positive cells was observed by immunochemistry study. RESULTS: trkB mRNA level in the lung tissue of rats with brain ischemia presented a significant increase, in corresponding to the upregulation of BDNF protein levels, when compared with sham one (P<0.05). trkB was localized in endothelia cells and smooth muscle. CONCLUSION: The upregulated expression of trkB expression may be associated with lung injury after brain ischemia.

[Expression changes of MEK in lung of rats subjected to brain ischemia].

OBJECTIVE: To explore the expression changes of mitogen extracellular kinase (MEK) in injured lung after brain ischemia in rats. METHODS: Adult SD rats were assigned randomly to sham operation group and brain ischemia lung injury (BILI) group. Rats in BILI group were subjected brain ischemia and allowed to survived 3 d. Pathalogical changes in lung were indicated by HE staining. The MEK expression was determined by RT-PCR and Western blot technique. RESULTS: After brain ischemia, the bulk of inflammatory cells invaded into lung were observed. Upregulated level of MEK mRNA and protein were found at 3 days after ischemia (P<0.05). CONCLUSION: The upregulated expression of MEK implied that the MEK may play some roles in lung injury after brain ischemia.

[Expression of TNF-alpha in lung tissue of rats with lung injury induced by brain ischemia].

OBJECTIVE: To investigate the expression of tumor necrosis factor-alpha (TNF-alpha) in the lung tissue of rats with lung injury induced by brain ischemia. METHODS: The rat model of lung injury induced by brain ischemia was established. At 24 h, 48 h, 72 h after brain ischemia, lung tissues were harvested from each rats, the expressions of TNF-alpha mRNA and protein and its distributions in the lung tissue were measured by the methods of RT-PCR (n=8), Western blot (n=8), and immunohistochemistry (n=5), respectively. RESULTS: The increase of TNF-alpha mRNA and protein levels were found in the lung tissues after brain ischemia, when compared with sham group (P<0.05). The morphological study with immunohistochemical staining observed TNF-alpha positive reaction in epithelial cells and some macrophages in the lung tissues after brain ischemia. CONCLUSION: The expression of TNF-alpha in the lung tissue could be upregulated in the rats with brain ischemia.

[Expression changes of IL-1beta in lung of rats subjected to brain ischemia].

OBJECTIVE: To study the expression changes of interleukin-1beta (IL-1beta) in the lung of rats with brain ischemia. METHODS: Adult SD rats were divided into sham operation group and brain ischemia lung injury (BILI) group randomly. Focal cerebral ischemia inflammatory lung injury model was developed with intraluminal thread technique. Lungs were harvested from rats at different time point respectively. RT-PCR (24 h), Western blot (48 h) and immunohistochemistry (72 h) were employed to detect the expressional changes and the distributions of IL-1beta in the lung tissues. RESULTS: IL-1beta immunohistochemical positive reaction was observed in epithelia cell and neutrophil as well as macrophage. Increased protein level and mRNA expression for IL-1beta were found in lung after brain ischemia compared with those of sham group. CONCLUSION: IL-1beta, as a crucial inflammatory factor, could be associated with airway inflammation in lung following brain ischemia in rats.

[Effects of BDNF antibody block on IL-6 expression in lung of rats subjected to brain ischemia].

OBJECTIVE: To explore effect of brain-derived neurotrophic factor (BDNF) on IL-6 expression in the lung of rats with brain ischemia. METHODS: Inflammatory lung injury was induced by brain ischemia in rats that were devided into sham operation group, brain ischemia lung injury (BILI) group and brain ischemia with BDNF administration group. Lungs were harvested from rats in each group in 3 days after brain ischemia respectively. Immunohistochemistry, RT-PCR and Western blot were employed to detect the expressional changes on the mRNA and protein of IL-6 in the lung tissues. RESULTS: Expression of IL-6 was mainly found in cytoplasm of lung epithelial cell and macrophage with immunohistochemistry staining. A significant decrease of IL-6 expression was observed at 3 days after brain ischemia with BDNF antibody block. CONCLUSION: BDNF, as a crucial neurotrophic factor, could regulate IL-6 expression in rats lung tissues with brain ischemia.

[Effects of BDNF antibody to block IL-1beta expression and lung injury in rats subjected to brain ischemia].

OBJECTIVE: To explore the effects of brain-derived neurotrophic factor (BDNF) antibody to block lung injury and interleukin-1beta (IL-1beta) expression in the rats with brain ischemia. METHODS: Thirty nine SD rats were divided into sham group, brain ischemia lung injury (BILI) group, and BDNF antibody treated group. Inflammatory lung injury was induced by brain ischemia in the later two groups, and BDNF antibody was given through intraperitoneal injection to the rats for 3 days in BDNF antibody group. Lung tissue samples were harvested from the rats in each group at the 3rd day after brain ischemia. Lung edema degree was evaluated by HE staining. The protein expressions of IL-1beta in the lung tissues were measured by the methods of immunohistochemistry (n=5) and Western blot (n=8). RESULTS: The increased immunostaining of IL-1beta were found in the lung tissue at 3 days after brain ischemia, which indicated the upregulated expression of IL-1beta protein in the lung injury induced by cerebral ischemia. The block of BDNF antibody resulted in a significant decrease of IL-1beta expression, as well as the decrease of lung edema. CONCLUSION: BDNF, as a crucial factor, could regulate airway inflammation injury in brain ischemia rats via activating IL-1beta expression.