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Cigarette smoking is a well-established risk factor for various diseases, such as cardiovascular diseases, neurodegeneration, and cancer. Cadmium nitrate (Cd(NO3)2) is one of the major products from the cigarette smoke. Up to now, no supporting evidence on Cd(NO3)2-induced apoptosis and its related working mechanism in neurons has been found. In present study, the mode of cell death, caspase activities, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in N2a cells, which are neuron-like cells, were assessed by Annexin V-FITC and PI assays, caspase fluorometric assay, DCFH-DA fluorescence assay, and JC-1 fluorescence assay respectively. The results showed that not only Cd(NO3)2 induced apoptosis and necrosis but also the activities of caspase-3 and -9 expressed in a concentration-dependent manner. In addition, Cd(NO3)2 also induced both mitochondrial dysfunction and ROS generation in a concentration-dependent manner. All these indicated that in N2a cells parallel trends could be observed in apoptosis, caspase-3 and -9 activities, mitochondrial dysfunction, and ROS generation when induced by Cd(NO3)2. Furthermore, Cd(NO3)2-induced apoptosis, caspases activities, mitochondrial dysfunction, and ROS generation were reduced by N-acetyl-l-cysteine (NAC). These results indicated that Cd(NO3)2-induced neuronal apoptosis was reduced by NAC via intrinsic apoptotic caspase cascade activities and their up-stream factors, including mitochondrial dysfunction and ROS generation.

Safrole is a natural compound categorized as a group 2B carcinogen extracted from betel quid chewing, which is a common practice of psychoactive habits integrated into social and cultural ceremonies among serveral million people, especially in Southern or Southeastern Asia. Safrole is one of the major risk compunds for development of oral squamous cell carcinoma and hepatocellular carcinoma via DNA adduction. In innate immunity, macrophages are the predominant cells for non-specific first line defense against pathogens in oral tissue. Up to now, there is no evidence to implicate the potential toxicological effect of safrole on macrophages. In this study, we found safrole induced the generation of reactive oxygen species (ROS) and myeloperoxidase (MPO) in RAW264.7 macrophages in a concentration-dependent manner. Furthermore, cytotoxicity, DNA damage, and apoptosis were caused by safrole in a concentration-dependent manner. While the activation of antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) was reduced, the phosphorylation of Akt was induced by safrole in a concentration-dependent manner. These results indicated that the induction of cytotoxicity, DNA damage, and apoptosis in macrophages by safrole was through generation of ROS and inhibition of antioxidative enzymes possibly via Akt phosphorylation.

Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality rates mainly caused by Gram-negative bacteria. Nevertheless, an effective treatment strategy for ALI is yet to be developed. Zerumbone, a sesquiterpene isolated from Zingiber zerumbet Smith, possesses several advantageous bioeffects such as antioxidation, anti-inflammation, and antiulcer. Pretreatment of zerumbone inhibited lipopolysaccharide (LPS)-induced arterial blood gas exchange, neutrophils infiltration, and increased pulmonary vascular permeability. LPS-induced expression of intercellular adhesion molecule-1 (ICAM-1) was inhibited by zerumbone at a lower concentration than that of vascular cell adhesion molecule-1 (VCAM-1). In addition, proinflammatory cytokines, such as interleukin (IL)-1β and macrophage inflammatory protein (MIP)-2 were suppressed by zerumbone. The phosphorylation of nuclear factor (NF)-κB, a proinflammatory transcription factor, and degradation of inhibitor of κB (IκB), an inhibitor of NF-κB, were also reduced by zerumbone. Furthermore, we found the inhibitory concentration of zerumbone on phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was lower than that of extracellular signal-regulated kinase (ERK). In conclusion, zerumbone could be a potential protective agent for ALI, possibly via expression of ICAM-1, IL-1β, and MIP-2. The protective mechanism of zerumbone was by reversing the activation of p38 MAPK/JNK-IκB/NF-κB pathway.

There are voluminous ultrahigh pressure-related orthogneisses and minor metamorphic supracrustal rocks in the northeastern Sulu UHP terrane (NSL), East China. The tectonic affinities of the supracr...

Nerve decompression is an essential therapeutic strategy for pain relief clinically; however, its potential mechanism remains poorly understood. Opioid analgesics acting on opioid receptors (OR) within the various regions of the nervous system have been used widely for pain management. We therefore hypothesized that nerve decompression in a neuropathic pain model of chronic constriction injury (CCI) improves the synaptic OR plasticity in the dorsal horn, which is in response to alleviate pain hypersensitivity. After CCI, the Sprague-Dawley rats were assigned into Decompression group, in which the ligatures around the sciatic nerve were removed at post-operative week 4 (POW 4), and a CCI group, in which the ligatures remained. Pain hypersensitivity, including thermal hyperalgesia and mechanical allodynia, was entirely normalized in Decompression group within the following 4 weeks. Substantial reversal of mu- and delta-OR immunoreactive (IR) expressions in Decompression group was detected in primary afferent terminals in the dorsal horn. In Decompression group, mu-OR antagonist (CTOP, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 [Disulfide Bridge: 2-7]) and delta-OR antagonist (NTI, 17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan hydrochloride) re-induced pain hypersensitivity by intrathecal administration in a dose-responsive manner. Additionally, mu-OR agonist (DAMGO, [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin) and delta-OR agonist (SNC80, ((+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide) were administrated intrathecally to attenuating CCI-induced chronic and acute pain hypersensitivity dose-dependently. Our current results strongly suggested that nerve decompression provides the opportunity for improving the synaptic OR plasticity in the dorsal horn and pharmacological blockade presents a novel insight into the therapeutic strategy for pain hypersensitivity.

Zerumbone, a cyclic eleven-membered sesquiterpene, is the major component of the essential oil isolated from the wild ginger, Zingiber zerumbet. There are several beneficial pharmacological activities of zerumbone including anti-inflammatory, antioxidant, and anticancer activities. Acute lung injury (ALI) is an acute pulmonary inflammatory disorder with high morbidity and mortality rate. In present study, we aimed to investigate the protective effects and mechanisms of zerumbone on endotoxin, lipopolysaccharide (LPS)-induced ALI. Mice were pretreated with zerumbone at various concentrations for 30 min followed by intratracheal administration of LPS for 6 h. Pretreatment with zerumbone not only reduced leukocytes infiltration into the alveolar space but also inhibited lung edema in LPS-induced ALI. Decreased secretion of proinflammatory cytokines such as TNFα and IL-6 caused by LPS were reversed by zerumbone. LPS-induced expressions of proinflammatory mediators, iNOS and COX-2, were inhibited by zerumbone. In addition, NFκB activation and Akt phosphorylation were inhibited by zerumbone in LPS-induced ALI. All these results suggested that the protective mechanisms of zerumbone on endotoxin-induced ALI were via inhibition of Akt-NFκB activation.

Acute lung injury (ALI) is a serious disease with high morbidity and mortality rate. Although there are effective strategies for treatment of ALI; a widely accepted specific pharmacotherapy has not yet established. Zerumbone, the major active phytochemical compound from Zingiber zerumbet Smith, exhibits various beneficial biological and pharmacological activities, such as antioxidation, anti-inflammation, immunomodulation, and anti-cancer. We aimed to study the potential protective effects and mechanisms of zerumbone in mouse model of lipopolysaccharide (LPS)-induced ALI. Pretreatment with zerumbone inhibited the histopatholgical changes such as neutrophils infiltration, increased in alveolar barrier thickness, hemorrhage, and hyaline membrane formation occurred in lungs in LPS-induced ALI. In addition, not only LPS-induced activation of myeloperoxidase (MPO) and metallopeptidase-9 (MMP-9) was suppressed by zerumbone, but also lipid peroxidation in lungs was inhibited as well. Moreover, pretreatment with zerumbone reversed the antioxidative enzymes activities, including superoxide dismutase, catalase, and glutathione peroxidase, decreased by LPS and enhanced the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) induced by LPS. These results from present study suggested that the protective mechanisms of zerumbone on LPS-induced ALI were via up-regulation of antioxidative enzymes and Nrf2/HO-1 pathway.

Background Postoperative sepsis is a major type of sepsis. Sociodemographic characteristics, incidence trends, surgical procedures, comorbidities, and organ system dysfunctions related to the disease burden of postoperative sepsis episodes are unclear. Methods We analyzed epidemiological characteristics of postoperative sepsis based on the ICD-9-CM codes for the years 2002 to 2013 using the Longitudinal Health Insurance Databases of Taiwan’s National Health Insurance Research Database. Results We identified 5,221 patients with postoperative sepsis and 338,279 patients without postoperative sepsis. The incidence of postoperative sepsis increased annually with a crude mean of 0.06% for patients aged 45–64 and 0.34% over 65 years. Patients with postoperative sepsis indicated a high risk associated with the characteristics, male sex (OR:1.375), aged 45–64 or ≥ 65 years (OR:2.639 and 5.862), low income (OR:1.390), aged township (OR:1.269), agricultural town (OR:1.266), and remote township (OR:1.205). Splenic surgery (OR:7.723), Chronic renal disease (OR:1.733), cardiovascular dysfunction (OR:2.441), and organ system dysfunctions had the highest risk of postoperative sepsis. Conclusion Risk of postoperative sepsis was highest among men, older, and low income. Patients with splenic surgery, chronic renal comorbidity, and cardiovascular system dysfunction exhibited the highest risk for postoperative sepsis. The evaluation of high-risk factors assists in reducing the disease burden.

Bisphenol A (BPA) is primarily used in production of polycarbonate plastics and epoxy resins including plastic containers. BPA is an endocrine disruptor and supposes to induce asthma and cancer. However, so far only a few evidences have shown the BPA-induced toxic effect and its related mechanism in macrophages. BPA demonstrated cytotoxic effect on RAW264.7 macrophages in a concentration and time-dependent manner. BPA induces necrosis, apoptosis, and genotoxicity in a concentration-dependent manner. Phosphorylation of cytochrome C (cyto C) and p53 was due to mitochondrial disruption via BCL2 and BCL-XL downregulation and BAX, BID, and BAD upregulation. Both caspase-dependent, including caspase-9, caspase-3, and PARP-1 cleavage, and caspase-independent, such as nuclear translocation of AIF, pathways were activated by BPA. Furthermore, generation of reactive oxygen species (ROS) and reduction of antioxidative enzyme activities were induced by BPA. Parallel trends were observed in the effect of BPA on cytotoxicity, apoptosis, genotoxicity, p53 phosphorylation, BCL2 family expression exchange, caspase-dependent and independent apoptotic pathways, and ROS generation in RAW264.7 macrophages. Finally, BPA-exhibited cytotoxicity, apoptosis, and genotoxicity could be inhibited by N-acetylcysteine. These results indicated that the toxic effect of BPA was functioning via oxidative stress-associated mitochondrial apoptotic pathway in macrophages.

When a science park or a technology park react to a transformation in the world, it becomes important to determine how to eliminate components with poor performance that have not contributed to the country’s overall research and development targets. The theory and goal of competitiveness clusters and technology parks in France is similar. The territory of the Technology Park is a type of organization with a structure that can be re-organized, just as the concept of Fractal Theory, to become diversified into an organization through re-organization. This study uses the Fuzzy Delphi method to investigate France and Taiwan’s innovation strategies by analysing the degree of recognition of park evaluation items in an expert questionnaire as a preliminary study of park evaluation in developing Science Parks in Taiwan.

Acute lung injury (ALI) is a serious inflammatory disorder which remains the primary cause of incidence and mortality in patients with acute pulmonary inflammation. However, there is still no effective medical strategy available clinically for the improvement of ALI. Wogonin, isolated from roots of Scutellaria baicalensis Georgi, is a common medicinal herb which presents biological and pharmacological effects, including antioxidation, anti-inflammation, and anticancer. Preadministration of wogonin inhibited not only lung edema but also protein leakage into the alveolar space in murine model of lipopolysaccharide (LPS)-induced ALI. Moreover, wogonin not only reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) induced by LPS. We further found wogonin inhibited the phosphorylation of p38 MAPK and JNK at a concentration lower than ERK. In addition, inhibition of lung edema, protein leakage, expression of iNOS and COX-2, and phosphorylation of p38 MAPK and JNK were all observed in a parallel concentration-dependent manner. These results suggest that wogonin possesses potential protective effect against LPS-induced ALI via downregulation of iNOS and COX-2 expression by blocking phosphorylation of p38 MAPK and JNK. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 397-403, 2017.

Objectives Neutrophil infiltration into the lung is the critical characteristic of acute lung injury (ALI), which is a clinical state with acute inflammatory syndrome. Up to now, there is no effective medicine for ALI. Wogonin has been shown to posses serval biological activities including anti-inflammation, anti-oxidant and anti-carcinoma. Methods Acute lung injury was induced by intratracheal injection of LPS, and wogonin at various concentrations was injected intraperitoneally 30 min prior to LPS. Contents of myeloperoxidase (MPO) and expression of chemokines and adhesion molecules were determined by commercially and ELISA assay kits, respectively. Akt phosphorylation and RhoA activation were measured by western blot and RhoA pull-down activation assay, respectively. Key finding Neutrophil infiltration was reduced by wogonin in a concentration-dependent manner in the LPS-induced ALI mice model. LPS-induced proinflammatory cytokines and adhesion molecules were inhibited by wogonin in bronchoalveolar lavage fluid (BALF) with LPS-induced ALI. Furthermore, wogonin suppressed Akt phosphorylation and RhoA activation in lungs in LPS-induced ALI. The similar parallel trend was observed as wogonin reduced LPS-induced neutrophils infiltration, proinflammatory cytokines generation, adhesion molecules expression, Akt phosphorylation, and RhoA activation. Summary These results suggested that the effects of wogonin in LPS-induced ALI were induced by inhibition of Akt phosphorylation and RhoA activation.

Up to date, the morbidity and mortality rates of acute lung injury (ALI) still rank high among clinical illnesses. Endotoxin, also called lipopolysaccharide (LPS), induced sepsis is the major cause for ALI. Beneficial biological effects, such as antioxidation, anti-inflammation, and neuroprotection was found to express by 5,7-dihydroxy-8-methoxyflavone (DHMF). The purpose of present study was to investigate the potential protective effects of DHMF and the possibile mechanisms involved in LPS-induced ALI. In our experimental model, ALI was induced in mice by intratracheal injection of LPS, and DHMF at various concentrations was injected intraperitoneally for 30 min prior to LPS administration. Pretreatment with DHMF inhibited not only the histolopatholgical changes occurred in lungs but also leukocytes infiltration in LPS-induced ALI. Decreased activity of antioxidative enzymes (AOE) such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) caused by LPS was reversed by DHMF. LPS-induced lipid peroxidation HIF-1α accumulation, NF-κB phosphorylation, and IκBα degradation were all inhibited by DHMF. In addition, LPS-induced expression of proinflammatory mediators such as TNF-α and IL-1β were also inhibited by 5,7-dihydroxy-8-methoxyflavone. These results suggested that the protective mechanisms of DHMF on endotoxin-induced ALI might be via up-regulation of antioxidative enzymes, inhibition of NFκB phosphorylation, and HIF-1α accumulation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1700-1709, 2016.

Solvothermal reactions of Cd(II) or Mn(II) ions with 4׳-(4-carboxylphenyl)-2,2׳:6׳,2"-terpyridine acid (Hcpt) and thiophene-2,5-dicarboxylic acid (H2tpd) resulted in the formation of two isostructrual coordination networks {[M2(cpt)2(tpd)]·3.5H2O}n (M=Cd, 1; M=Mn, 2). These complexes have been characterized by single-crystal X-ray diffraction analyses, infrared spectra (IR), elemental analyses, and powder X-ray diffraction (PXRD). Complexes 1 and 2, formed by the cpt− and tpd2− bidentate connectors, have a 3D framework with a 3-connected, uninodal 103-ths topology possessing an unusual eight-fold [4*2] interpenetration mode. In addition, the ths cage has a long intracage M⋯M distance. In contrast, only a 1D coordination network {[CdCl(cpt)]·3.75H2O}n (3) was obtained under similar conditions while in the absence of the H2tpd ligand. Compound 3 is propagated only by the [CdCl(cpt)] unit, which illustrated that the incorporation of the cpt− and Cl− ligands to form a 1D network. The distinct ancillary anions (tpd2− or Cl−) play a critical role in determining the coordination features and the network connectivity of metal ions. This work presents a successful route to preparing rare eight-fold [4*2] interpenetrated networks.

Lipopolysaccharide (LPS), also called endotoxin, is the important pathogen of acute lung injury (ALI), which is a clinical syndrome that still lacks effective therapeutic medicine. Rutin belongs to vitamin P and possesses various beneficial effects. In this study, we investigate the potential protective effects and the mechanisms of rutin on LPS-induced ALI. Pre-administration with rutin inhibited LPS-induced arterial blood gas exchange and neutrophils infiltration in the lungs. LPS-induced expression of macrophage inflammatory protein (MIP)-2 and activation of matrix metalloproteinase (MMP)-9 were suppressed by rutin. In addition, the inhibitory concentration of rutin on phosphorylation of Akt was similar as MIP-2 expression and MMP-9 activation. In conclusion, rutin is a potential protective agent for ALI via suppressing the blood gas exchange and neutrophil infiltration. The mechanism of rutin is down-regulation of MIP-2 expression and MMP-9 activation through inhibition of Akt phosphorylation.

Endotoxins exist anywhere including in water pools, dust, humidifier systems, and machining fluids. The major causal factor is endotoxins in many serious diseases, such as fever, sepsis, multi-organ failure, meningococcemia, and severe morbidities like neurologic disability, or hearing loss. Endotoxins are also called lipopolysaccharide (LPS) and are important pathogens of acute lung injury (ALI). Rutin has potential beneficial effects including anti-inflammation, antioxidation, anti-hyperlipidemia, and anti-platelet aggregation. Pre-treatment with rutin inhibited LPS-induced neutrophil infiltration in the lungs. LPS-induced

Signal source is an important part of modern electronic system and has a wide range of applications in the fields of communication, measuring & control, navigation and medical care. This project developed a new dual-channel sine wave generator with Tunable Phase Difference on the basis of the direct digital frequency synthesis (DDS) technology. Design was accomplished using STC89C52 MCU and FPGA as the control center, integrating basic operation circuit and employing low-pass filter and the necessary software algorithm. The experimental results showed that the system can produce dual sine waves with tunable phase difference in 0~359° range. The system is stable in work and it is easy to adjust parameters.

Acute lung injury (ALI) is a serious disease with unacceptably high mortality and morbidity rates. Up to now, no effective therapeutic strategy for ALI has been established. Rutin, quercetin-3-rhamnosyl glucoside, expresses a wide range of biological activities and pharmacological effects, such as anti-inflammatory, antihypertensive, anticarcinogenic, vasoprotective, and cardioprotective activities. Pretreatment with rutin inhibited not only histopathological changes in lung tissues but also infiltration of polymorphonuclear granulocytes into bronchoalveolar lavage fluid in lipopolysaccharide (LPS)-induced ALI. In addition, LPS-induced inflammatory responses, including increased secretion of proinflammatory cytokines and lipid peroxidation, were inhibited by rutin in a concentration-dependent manner. Furthermore, rutin suppressed phosphorylation of NF-κB and MAPK and degradation of IκB, an NF-κB inhibitor. Decreased activities of antioxidative enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1 caused by LPS were reversed by rutin. At the same time, we found that ALI amelioration by chelation of extracellular metal ions with rutin is more efficacious than with deferoxamine. These results indicate that the protective mechanism of rutin is through inhibition of MAPK-NF-κB activation and upregulation of antioxidative enzymes.

Acute lung injury (ALI) presents high mortality and morbidity clinically and by far no effective preventive strategy has been established. Extract of Ginkgo biloba leaves, EGb 761, is a complex mixture that possesses several clinical beneficial effects such as anti-oxidation, anti-inflammation, anti-tumor, and cardioprotective property. With EGb 761 pretreatment, both lipopolysaccharide (LPS)-induced protein leakage and neutrophil infiltration, and LPS-induced inflammatory responses including increased myeloperoxidase (MPO) activity, lipid peroxidation, and metalloproteinase (MMP)-9 activity, were inhibited; LPS-suppressed activation of antioxidative enzymes (AOE) were reversed; and not only the phosphorylation of NF-κB but also the degradation of its inhibitor, IκB, were suppressed. These results suggested that the protection mechanism of EGb 761 is by inhibition of NFκB activation, possibly via the up-regulation of antioxidative enzymes. More studies are needed to further evaluate whether EGb 761 is a suitable candidate as an effective dietary strategy to reduce the incidence of endotoxin-induced ALI.

Microglia are the major component of intrinsic brain immune system in neuroinflammation. Although wogonin expresses anti-inflammatory function in microglia, little is known about the molecular mechanisms of the protective effect of wogonin against microglia activation. The aim of this study was to evaluate how wogonin exerts its anti-inflammatory function in BV2 microglial cells after LPS/INFγ administration. Wogonin not only inhibited LPS/ INFγ-induced PGE2 and NO production without affecting cell viability but also exhibited parallel inhibition on LPS/INFγ-induced expression of iNOS and COX-2 in the same concentration range. While LPS/INFγ-induced expression of P-p65 and P-IκB was inhibited by wogonin—only weak inhibition on P-p38 and P-JNK were observed, whereas it significantly attenuated the P-ERK1/2 and its upstream activators P-MEK1/2 and P-Src in a parallel concentration-dependent manner. These results indicated that the blockade of PGE2 and NO production by wogonin in LPS/INFγ-stimulated BV2 cells is attributed mainly to interference in the Src-MEK1/2-ERK1/2-NFκB-signaling pathway. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1162–1170, 2014.

Sophia-Atipolis Technology Park and Hsinchu Science Park has been over thirty years. This study analyzed French and Taiwan's innovation strategies in measures and tools, used Literature Reviews and Inductive Method to analyze and compare innovation strategies of France and Taiwan.

The toxicity of dental materials has raised public concern over the past years. One of the most commonly used methacrylic monomers for building the three-dimensional structure of the dental resin composites is 2,2-bis[4-(acryloxypropoxy)phenyl]propane (BAPP). The purpose of this study is to evaluate the potential toxicological implication of BAPP on human gingival fibroblasts (HGFs). Flow cytometric, fluorometric, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assays were used to detect the mode of cell death, caspase activities, and cell viability, respectively. In addition, alkaline single-cell gel electrophoresis (COMET) and cytokinesis block micronucleus (MN) assays were applied to evaluate the genotoxicity. According to the results BAPP demonstrated a cytotoxic effect on HGFs in a dose- and time-dependent manner. With increasing concentrations of BAPP, the mode of cell death shifted from apoptosis to necrosis, and the activities of caspases 3, 8, and 9 were also significantly induced. Moreover, a dose-related increase in the number of micronucleus and DNA strand breaks hinted at the expression of genotoxicity by BAPP. In conclusion, the results gathered from this study had demonstrated that BAPP-induced cytotoxicity and genotoxicity on HGFs were mediated by DNA damage and the activation of caspases 3, 8, and 9.

Acute lung injury (ALI) in critically ill patients remains the leading cause of mortality and morbidity. Lipopolysaccharide (LPS) is a key mediator of lung injury. This study investigates the protective effects and mechanisms of luteolin in intratracheal instillation of LPS (100μg)-induced ALI in mice. Pretreatment of mice with 70μmol/kg luteolin significantly restores LPS-induced decrease in oxygen pressure and increase in carbon dioxide in arterial blood. The histopathological study established 70μmol/kg luteolin pretreatment markedly attenuates lung histopathological changes, such as haemorrhaging, interstitial edema, and infiltration of polymorphonuclear neutrophils (PMNs) into the lung parenchyma and alveolar spaces. Sufficient evidence for luteolin (35 and 70μmol/kg) suppresses activation and infiltration of PMNs is obtained in expression of surface marker CD11b and Ly6G on cells in bronchoalveolar lavage fluid (BALF) cells and myeloperoxidase activity in lung tissue. Furthermore, luteolin reduces the activity of catalase and superoxide dismutase, and the level of oxidative damage, and lipid peroxidation, in lung tissue. In addition, the secretion of TNF-α, KC, and ICAM-1 in the BALF after LPS challenge are also inhibited by luteolin. Moreover, luteolin reduced LPS-induced activation of MAPK and NFκB pathways. Therefore, luteolin is a potential protective antagonists for LPS-induced ALI in mice.

We study the cytotoxicity of indium chloride (InCl₃) in Chinese hamster lung fibroblasts, the V79 cells, using MTT assay. The results showed that InCl₃ did not induce significant cytotoxicity at various concentrations tested. In addition, the frequency of micronuclei (MN) was assayed to evaluate the genotoxic effects of InCl₃ in V79 cells. InCl₃ at concentrations ranged 0.1-1 μM significantly increased MN frequency in a concentration-dependent manner. Both catalase and superoxide dismutase at concentrations of 75 and 150 μg/mL significantly inhibited InCl₃-induced MN. Similarly, Germanium oxide (GeO₂) and dimercaprol expressed antigenotoxic effects. From these findings, it is concluded that InCl₃ is a potent genotoxic chemical, which may be mediated partly by inducing oxidative stress. The significance of this study shows that the workers in the semiconductor factories should be cautious in exposing to the hazardous genotoxic InCl₃.

Chinese hamster ovary (CHO) cells, its lung fibroblasts (V79), and human lymphocytes are routinely used in in vitro cytogenetic assays, which include micronuclei (MN), sister chromatid exchange (SCE), and chromosome aberration (CA) assays. Mitomycin C (MMC), a DNA cross-link alkylating agent, is both an anticancer medicine and a carcinogen. To study the differential representative values of cell types in MMC-treated cytogenetic assays and its upstream factor, cysteine aspartic acid-specific protease (caspase)-3. Among the chosen cell types, lymphocytes expressed the highest sensitivity in all three MMC-induced assays, whereas CHO and V79 showed varied sensitivity in different assays. In MN assay, the sensitivity of CHO is higher than or equal to V79; in SCE assay, the sensitivity of CHO is the same as V79; and in CA assay, the sensitivity of CHO is higher than V79. In-depth analysis of CA revealed that in chromatid breaks and dicentrics formation, lymphocyte was the most sensitive of all and CHO was more sensitive than V79; and in acentrics and interchanges formation, lymphocyte was much more sensitive than the others. Furthermore, we found caspase-3 activity plays an important role in MMC-induced cytogenetic assays, with MMC-induced caspase-3 activity resulting in more sensitivity in lymphocytes than in CHO and V79. Based on these findings, lymphocyte will make a suitable predictive or representative control reference in cytogenetic assays and caspase-3 activity with its high specificity, positive predictive value, and sensitivity.

Acute lung injury (ALI) is a serious inflammatory disorder which remains the primary cause of incidence and mortality in patients with acute pulmonary inflammation. However, there is still no effective medical strategy available clinically for the improvement of ALI. Wogonin, isolated from roots of Scutellaria baicalensis Georgi, is a common medicinal herb which presents biological and pharmacological effects, including antioxidation, anti-inflammation, and anticancer. Preadministration of wogonin inhibited not only lung edema but also protein leakage into the alveolar space in murine model of lipopolysaccharide (LPS)-induced ALI. Moreover, wogonin not only reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) induced by LPS. We further found wogonin inhibited the phosphorylation of p38 MAPK and JNK at a concentration lower than ERK. In addition, inhibition of lung edema, protein leakage, expression of iNOS and COX-2, and phosphorylation of p38 MAPK and JNK were all observed in a parallel concentration-dependent manner. These results suggest that wogonin possesses potential protective effect against LPS-induced ALI via downregulation of iNOS and COX-2 expression by blocking phosphorylation of p38 MAPK and JNK. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 397-403, 2017.

Up to date, the morbidity and mortality rates of acute lung injury (ALI) still rank high among clinical illnesses. Endotoxin, also called lipopolysaccharide (LPS), induced sepsis is the major cause for ALI. Beneficial biological effects, such as antioxidation, anti-inflammation, and neuroprotection was found to express by 5,7-dihydroxy-8-methoxyflavone (DHMF). The purpose of present study was to investigate the potential protective effects of DHMF and the possibile mechanisms involved in LPS-induced ALI. In our experimental model, ALI was induced in mice by intratracheal injection of LPS, and DHMF at various concentrations was injected intraperitoneally for 30 min prior to LPS administration. Pretreatment with DHMF inhibited not only the histolopatholgical changes occurred in lungs but also leukocytes infiltration in LPS-induced ALI. Decreased activity of antioxidative enzymes (AOE) such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) caused by LPS was reversed by DHMF. LPS-induced lipid peroxidation HIF-1α accumulation, NF-κB phosphorylation, and IκBα degradation were all inhibited by DHMF. In addition, LPS-induced expression of proinflammatory mediators such as TNF-α and IL-1β were also inhibited by 5,7-dihydroxy-8-methoxyflavone. These results suggested that the protective mechanisms of DHMF on endotoxin-induced ALI might be via up-regulation of antioxidative enzymes, inhibition of NFκB phosphorylation, and HIF-1α accumulation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1700-1709, 2016.

Endotoxins exist anywhere including in water pools, dust, humidifier systems, and machining fluids. The major causal factor is endotoxins in many serious diseases, such as fever, sepsis, multi-organ failure, meningococcemia, and severe morbidities like neurologic disability, or hearing loss. Endotoxins are also called lipopolysaccharide (LPS) and are important pathogens of acute lung injury (ALI). Rutin has potential beneficial effects including anti-inflammation, antioxidation, anti-hyperlipidemia, and anti-platelet aggregation. Pre-treatment with rutin inhibited LPS-induced neutrophil infiltration in the lungs. LPS-induced expression of vascular cell adhesion molecule (VCAM)-1 and inducible nitric oxide synthase (iNOS) was suppressed by rutin, but there was no influence on expression of intercellular adhesion molecule-1 and cyclooxygenase-2. In addition, activation of the nuclear factor (NF)κB was reduced by rutin. Furthermore, we found that the inhibitory concentration of rutin on expression of VCAM-1 and iNOS was similar to NFκB activation. In conclusion, rutin is a potential protective agent for ALI via inhibition of neutrophil infiltration, expression of VCAM-1 and iNOS, and NFκB activation.

Wogonin is a flavonoid compound which exhibits antioxidation, anti-inflammation, neuroprotection, and antitumorgenesis functions. However, the mechanism of how wogonin reduces proinflammatory cytokine generation in activated microglia is unclear. At present, we found wogonin inhibited lipopolysaccharide (LPS)-/interferon-γ (INF-γ)-induced generation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Wogonin exhibited parallel inhibition on LPS-/INF-γ-induced expression of IL-6 and TNF-α messenger RNA at the same concentration range. LPS-/INF-γ-induced phosphorylation of signal transduction and transcription 1 and 3 (STAT1/3) were also inhibited by wogonin. Although wogonin expressed only weak inhibitory effect on LPS-/INF-γ-induced phosphorylation of Janus kinase-2 (Jak-2) and tyrosine kinase (Tyk)-2, it significantly attenuated the phosphorylation of Jak-1 and Jak-3. These results indicated that the blockade of IL-6 and TNF-α production by wogonin in LPS-/INF-γ-stimulated BV2 microglial cells was attributed mainly to the interference in Jak-1/-3-STAT1/3 signaling pathway.

Acute lung injury (ALI), instilled by lipopolysaccharide (LPS), is a severe illness with excessive mortality and has no specific treatment strategy. Luteolin is an anti-inflammatory flavonoid and widely distributed in the plants. Pretreatment with luteolin inhibited LPS-induced histological changes of ALI and lung tissue edema. In addition, LPS-induced inflammatory responses, including increased vascular permeability, tumor necrosis factor (TNF)-αand interleukin (IL)-6 production, and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), were also reduced by luteolin in a concentration-dependent manner. Furthermore, luteolin suppressed activation of NFκB and its upstream molecular factor, Akt. These results suggest that the protection mechanism of luteolin is by inhibition of NFκB activation possibly via Akt.

We study the cytotoxicity of indium chloride (InCl₃) in Chinese hamster lung fibroblasts, the V79 cells, using MTT assay. The results showed that InCl₃ did not induce significant cytotoxicity at various concentrations tested. In addition, the frequency of micronuclei (MN) was assayed to evaluate the genotoxic effects of InCl₃ in V79 cells. InCl₃ at concentrations ranged 0.1-1 μM significantly increased MN frequency in a concentration-dependent manner. Both catalase and superoxide dismutase at concentrations of 75 and 150 μg/mL significantly inhibited InCl₃-induced MN. Similarly, Germanium oxide (GeO₂) and dimercaprol expressed antigenotoxic effects. From these findings, it is concluded that InCl₃ is a potent genotoxic chemical, which may be mediated partly by inducing oxidative stress. The significance of this study shows that the workers in the semiconductor factories should be cautious in exposing to the hazardous genotoxic InCl₃.

Three-dimensional computed tomography (3D-CT) not only allows accurate preoperative delineation of the lesions but also provides precise pathomechanic diagnosis for planning the most effective treatment to avoid respiratory compromise. In a 10-month-old baby girl, who was ventilator-dependent after successful correction of double outlet right ventricle (DORV), flexible fiberoptic bronchoscopy (FFB) revealed the new formation of postoperative airway obstruction over the right main bronchus (RMB) and obstructed right tracheal bronchus (RTB). 3D-CT demonstrated tracheobronchial obstruction (TBO) was caused by the dilated ascending aorta (AAo) and right pulmonary artery (RPA). Sequential treatments including artery pexy of AAo and RPA and balloon dilatation (BD) of the stenotic RTB and RMB had successfully restored the airway patency. The patient was successfully weaned from ventilator 2 days after treatments and has shown no respiratory difficulty thus far. Thus, the impact of preoperative 3D-CT on planning treatment cannot be emphasized.

Background Spared nerve injury is an important neuropathic pain model for investigating the role of intact primary afferents in the skin on pain hypersensitivity. However, potential cellular mechanisms remain poorly understood. In phosphoinositide-3 kinase pathway, pyruvate dehydrogenase kinase 1 (PDK1) participates in the regulation of neuronal plasticity for central sensitization. The downstream cascades of PDK1 include: (1) protein kinase C gamma (PKCg) controls the trafficking and phosphorylation of ionotropic glutamate receptor; (2) protein kinase B (Akt)/the mammalian target of rapamycin (mTOR) signaling is responsible for local protein synthesis. Under these statements, we therefore hypothesized that an increase of PKCg activation and mTOR-dependent PKCg synthesis in intact primary afferents after SNI might contribute to pain hypersensitivity. Results The variants of spared nerve injury were performed in Sprague-Dawley rats by transecting any two of the three branches of the sciatic nerve, leaving only one branch intact. Following SNIt (spared tibial branch), mechanical hyperalgesia and mechanical allodynia, but not thermal hyperalgesia, were significantly induced. In the first footpad, normal epidermal innervations were verified by the protein gene product 9.5 (PGP9.5)- and growth-associated protein 43 (GAP43)-immunoreactive (IR) intraepidermal nerve fibers (IENFs) densities. Furthermore, the rapid increases of phospho-PKCg- and phosphomTOR-IR subepidermal nerve fibers (SENFs) areas were distinct gathered from the results of PGP9.5-, GAP43-, and neurofilament 200 (NF200)-IR SENFs areas. The efficacy of PKC inhibitor (GF 109203X) or mTOR complex 1 inhibitor (rapamycin) for attenuating mechanical hyperalgesia and mechanical allodynia by intraplantar injection was dose-dependent. Conclusions From results obtained in this study, we strongly recommend that the intact SENFs persistently increase PKCg activation and mTOR-dependent PKCg synthesis participate in the initiation and maintenance of mechanical hypersensitivity in spared nerve injury, which represents as a novel insight into the therapeutic strategy of pain in the periphery.