Pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, and epithelioid glioblastoma: Case series with clinical characteristics, molecular features and progression relationship.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and relationship with progression. METHODS: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enroled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumour tissue samples of the fourteen patients were examined by immunohistochemical staining (MGMT, VEGF, BRAF-V600E, etc.). RESULTS: The mean age of 13 patients with PXA or A-PXA was 25.4 years; twelve of these patients had tumours at supratentorial regions. VEGF positivity was detected in the tumour samples of 13 patients, MGMT positivity in 10 patients, and BRAF-V600E positivity in 7 patients. The recurrent tumour tissue of the patient with E-GBM arising from A-PXA was screened to detect 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next-generation sequencing (NGS). For the tumour sample of the E-GBM patient who survived for up to 11 years after the fourth resection, BRAF V600E was wild type in the sample obtained from the first surgery, while it was mutant in the second, third, and fourth surgeries. In contrast, the promoter status of MGMT in the four surgeries was unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second, third and fourth surgeries were 14.06%, 9.13% and 48.29%, respectively. CONCLUSIONS: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with the BRAF-V600E mutation.

Multistate transformations of a femtosecond fiber laser based on a pure fiber saturable absorber.

The graded index multimode-fiber step-index multimode fiber-graded index multimode fiber (GIMF-SIMF-GIMF) structure was designed as a saturable absorber (SA). To obtain optical pulses that meet the requirements of different applications, the multistate transformations of a femtosecond fiber laser based on GIMF-SIMF-GIMF SA were numerically and experimentally researched. The fiber laser can self-start mode-locking; its fundamental repetition rate of fiber laser is 10.35 MHz. The fiber laser can deliver three different optical pulses, namely, the conventional soliton, second-order bound state, and noise-like pulse. The duration of soliton is 421.2 fs; the energy of noise-like pulse is 197.10 pJ. The experimental and simulated results show that the output states of the fiber laser can be switched by adjusting the pump power.

Evolutions of Q-switched mode-locked square noise-like pulse with different cavity lengths.

A $Q$-switched mode-locked square noise-like pulse (QMLSNLP) is generated in a nonlinear polarization rotation passively mode-locked fiber laser. When the pump power changes from 154 mW to 414 mW, the frequency of the $Q$-switched envelope varies from 21.7 kHz to 38.9 kHz, while the duration of the $Q$-switched envelope decreases from $5.1\,\,{\unicode{x00B5}\rm s}$ to $3.2{\unicode{x00B5}\rm s}$, correspondingly. In the meantime, QMLSNLP keeps the fundamental repetition rate constant, and the pulse duration increases from 3.4 ns to 6.7 ns. By inserting different lengths of single-mode fiber into the ring cavity, the evolutions of QMLSNLP are measured and analyzed. According to the cavity parameters and experimental results, impacts of the cavity length on QMLSNLP are investigated in detail.

Integrated genomic and transcriptomic analysis suggests KRT18 mutation and MTAP are key genetic alterations related to the prognosis between astrocytoma and glioblastoma.

BACKGROUND: Astrocytoma and glioblastoma (GBM) are the two main subtypes of glioma, with the 2016 World Health Organization Classification of Tumors of the Central Nervous System (CNS WHO) classifying them into different grades. GBM is the most malignant among all CNS tumors with a 5-year survival rate of less than 5%. Although the prognosis of patients with astrocytoma is better than that of GBM in general, patients with anaplastic astrocytoma (AA) and isocitrate dehydrogenase (IDH) wild type have a similar prognosis as GBM and entail a high risk of progression. Exploring the molecular driving force behind the malignant phenotype of astrocytoma and GBM will help explain the diversity of glioma and discover new drug targets. METHODS: We enrolled 12 patients with astrocytoma and 12 patients with GBM and performed whole-exome sequencing (WES) and RNA sequencing analysis on tumor samples from the patients. RESULTS: We found that the somatic mutation of KRT18, which is associated with cell apoptosis and adhesion by interacting with receptor 1-associated protein (TRADD) and pinin, was significantly enriched in astrocytoma, but rare in GBM. Copy number loss of MTAP, which is closely related to a poor prognosis of glioma, was found to be significantly enriched in GBM. In addition, different somatic copy number alteration (SCNA), gene expression, and immune cell infiltration patterns between astrocytoma and GBM were found. CONCLUSIONS: This study revealed the distinct characteristics of astrocytoma and GBM at the DNA and RNA level. Somatic mutation of KRT18 and copy number loss of MTAP, two key genetic alterative genes in astrocytoma and GBM, have the potential to become therapeutic targets in glioma.

Unique genomic features and prognostic value of COSMIC mutational signature 4 in lung adenocarcinoma and lung squamous cell carcinoma.

BACKGROUND: Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, and prognosis. Among the signatures cataloged at COSMIC, mutational signature 4 has been linked to smoking. However, the distribution of signature 4 in Chinese lung cancer patients has not been evaluated, and its clinical value has not been evaluated. Here we survey mutational signatures in Chinese lung cancer patients and explore the relationship between signature 4 and other genomic features in the patients. METHODS: We extracted mutational signatures from whole-exome sequencing data of Chinese non-small cell lung cancer patients. The data included 401 lung adenocarcinoma (LUAD) and 92 squamous cell carcinoma (LUSC). We then performed statistical analysis to search for genomic and clinical features that can be linked to mutation signatures. RESULTS: We found signature 4 is the most frequent mutational signature in LUSC and the second most frequent in LUAD. Fifty-six LUAD and thirty-five LUSC patients were named with high signature 4 similarities (cosine similarity >0.7). These patients have shorter survival and higher tumor mutational burden comparing to those with low signature 4 similarities. Dozens of genes with single nucleotide variation, index mutations, and copy number variations were differentially enriched in the patients with high signature 4 similarities. Among these genes, CSMD3, LRP1B, TP53, SYNE1, SLIT2, FGF4, and FGF19 are common in both LUADs and LUSCs with high signature 4 similarities, showing that these genes are tightly associated with signature 4. CONCLUSIONS: The present study is the first to report a comparison in Chinese NSCLC patients with or without COSMIC mutational signature 4. These results will help find the Signature 4 related mutational process in NSCLC.

Rapid and precise phase retrieval from two-frame tilt-shift based on Lissajous ellipse fitting and ellipse standardization.

A rapid and precise phase-retrieval method based on Lissajous ellipse fitting and ellipse standardization is demonstrated. It only requires two interferograms without pre-filtering, which reduces its complexity and shortens the processing time. The elliptic coefficients obtained by ellipse fitting are used for ellipse standardization. After compensating phase-shift errors by ellipse standardization, the phase distribution is extracted with high precision. It is suitable for fluctuation, noise, tilt-shift, simple and complex fringes. This method is effective for the number of fringes less than 1. The reliability of the method is verified by simulations and experiments, indicating high accuracy and less time consumption.

The SIAH1-HIPK2-p53ser46 Damage Response Pathway is Involved in Temozolomide-Induced Glioblastoma Cell Death.

Patients suffering from glioblastoma have a dismal prognosis, indicating the need for new therapeutic targets. Here we provide evidence that the DNA damage kinase HIPK2 and its negative regulatory E3-ubiquitin ligase SIAH1 are critical factors controlling temozolomide-induced cell death. We show that HIPK2 downregulation (HIPK2kd) significantly reduces the level of apoptosis. This was not the case in glioblastoma cells expressing the repair protein MGMT, suggesting that the primary DNA lesion responsible for triggering HIPK2-mediated apoptosis is O6 -methylguanine. Upon temozolomide treatment, p53 becomes phosphorylated whereby HIPK2kd had impact exclusively on ser46, but not ser15. Searching for the transcriptional target of p-p53ser46, we identified the death receptor FAS (CD95, APO-1) being involved. Thus, the expression of FAS was attenuated following HIPK2kd, supporting the conclusion that HIPK2 regulates temozolomide-induced apoptosis via p-p53ser46-driven FAS expression. This was substantiated in chromatin-immunoprecipitation experiments, in which p-p53ser46 binding to the Fas promotor was regulated by HIPK2. Other pro-apoptotic proteins such as PUMA, NOXA, BAX, and PTEN were not affected in HIPK2kd, and also double-strand breaks following temozolomide remained unaffected. We further show that downregulation of the HIPK2 inactivator SIAH1 significantly ameliorates temozolomide-induced apoptosis, suggesting that the ATM/ATR target SIAH1 together with HIPK2 plays a proapoptotic role in glioma cells exhibiting p53wt status. A database analysis revealed that SIAH1, but not SIAH2, is significantly overexpressed in glioblastomas. IMPLICATIONS: The identification of a novel apoptotic pathway triggered by the temozolomide-induced DNA damage O6 -methylguanine supports the role of p53 in the decision between survival and death and suggests SIAH1 and HIPK2 as new therapeutic targets.

Pretreatment with the compound asperuloside decreases acute lung injury via inhibiting MAPK and NF-κB signaling in a murine model.

Asperuloside, an iridoid glycoside found in Herba Paederiae, is a component from traditional Chinese herbal medicine. In this study, we aimed to investigate the protective effects and potential mechanisms of asperuloside action on inflammatory responses in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and an LPS-induced lung injury model. The pro-inflammatory cytokines and signaling pathways were measured by enzyme-linked immunosorbent assays (ELISA) and Western blotting to determine the effects of asperuloside. We found that asperuloside can significantly downregulate tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, and IL-6 levels in vitro and in vivo, and treatment with asperuloside significantly reduced the lung wet-to-dry weight, histological alterations and myeloperoxidase activity in a murine model of LPS-induced acute lung injury (ALI). In addition, Western blot analysis that pretreatment with asperuloside remarkably blunted the phosphorylation of inhibitor of nuclear factor kappa-B (IκBα), extracellular signal-related kinases 1 and 2 (ERK1/2), c-Jun. N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) in LPS-stimulated inflammation. These results indicate that asperuloside exerts its anti-inflammatory effect in correlation with inhibition of a pro-inflammatory mediator through suppressing nuclear factor kappa-B (NF-κB) nuclear translocation and MAPK phosphorylation in a dose-dependent manner.

D(-)-Salicin inhibits the LPS-induced inflammation in RAW264.7 cells and mouse models.

D(-)-Salicin is a traditional medicine which has been known to exhibit anti-inflammation and other therapeutic activities. The present study aimed to investigate whether D(-)-Salicin inhibited the LPS-induced inflammation in vivo and in vitro. We evaluated the effect of D(-)-Salicin on cytokines (TNF-α, IL-1ß, IL-6 and IL-10) in vivo and in vitro by enzyme-linked immunosorbent assay and signaling pathways (MAPKs and NF-κB) in vivo by Western blot. The results showed that D(-)-Salicin markedly decreased TNF-α, IL-1ß and IL-6 concentrations and increased IL-10 concentration. In addition, western blot analysis indicated that D(-)-Salicin suppressed the activation of MAPKs and NF-κB signaling pathways stimulated by LPS. To examine whether D(-)-Salicin ameliorated LPS-induced lung inflammation, inhibitors of MAPKs and NF-κB signaling pathways were administrated intraperitoneally to mice. Interference with specific inhibitors revealed that D(-)-Salicin-mediated cytokine suppression was through MAPKs and NF-κB pathways. In the mouse model of acute lung injury, histopathologic examination indicted that D(-)-Salicin suppressed edema induced by LPS. So it is suggest that D(-)-Salicin might be a potential therapeutic agent against inflammatory diseases.

Asiaticoside attenuates lipopolysaccharide-induced acute lung injury via down-regulation of NF-κB signaling pathway.

Asiaticoside (AS), a triterpene glycoside isolated from Centella asiatica, has been shown to possess potent anti-inflammatory activity. However, the detailed molecular mechanisms of AS on lipopolysaccharide (LPS)-induced acute lung injury (ALI) model in mice are scanty. The purpose of this study was to evaluate the effect of AS on LPS-induced mouse ALI via down-regulation of NF-κB signaling pathway. We investigated the efficacy of AS on cytokine levels induced by LPS in bronchoalveolar lavage fluid (BALF) and RAW 264.7 cells. The production of cytokine (TNF-α and IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). The lung wet-to-dry weight ratios were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. To further study the mechanism of AS protective effects on ALI, the activation of NF-κB p65 subunit and the degradation of IκBα were tested by western blot assay. We found that AS treatment at 15, 30 or 45mg/kg dose-dependently attenuated LPS-induced pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, our results suggested that AS suppressed inflammatory responses in LPS-induced ALI through inhibition of the phosphorylation of NF-κB p65 subunit and the degradation of its inhibitor IκBα, and might be a new preventive agent of ALI in the clinical setting.

Betulin protects mice from bacterial pneumonia and acute lung injury.

Betulin, a naturally occurring triterpene, has shown anti-HIV activity, but details on the anti-inflammatory activity are scanty. In this study, we sought to investigate the effect of Betulin on LPS-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LPS or viable Escherichia coli (E. coli) in vivo. In vitro, Betulin inhibited LPS-induced tumor necrosis factor α (TNF-α) and (interleukin) IL-6 levels and up-regulated the level of IL-10. Also Betulin suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 protein in LPS-stimulated RAW 264.7 cells. In vivo, Betulin alleviated LPS-induced acute lung injury. Treatment with Betulin diminished pro-inflammatory cytokines, myeloperoxidase activity and bacterial loads in lung tissue during gram-negative pneumonia. Our findings demonstrated that Betulin inhibits pro-inflammatory responses induced by the gram-negative stimuli LPS and E. coli, suggesting that Betulin may represent a novel strategy for the treatment of lung inflammation.

Linalool attenuates lung inflammation induced by Pasteurella multocida via activating Nrf-2 signaling pathway.

Pasteurellosis caused by Pasteurella multocida manifest often as respiratory infection in farmed small ruminants. Although the incidence of pasteurellosis due to P. multocida mainly takes the form of pneumonia, there is limited information on host factors that play a role in disease pathogenesis in the milieu of host-pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a critical regulator for various inflammatory and immune responses by controlling oxidative stress, may play an important role in the processes of inflammation induced by P. multocida. In this study, linalool, a natural compound of the essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein translocation in the A549 lung cell line and in vivo. The P. multocida-induced pro-inflammatory cytokines expression was abrogated by Nrf-2 siRNA. Postponed treatment with linalool decreased lung neutrophil accumulation and enhanced clearance of P. multocida. Furthermore, linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6. In addition, animals treated with linalool had a marked improvement in survival. These findings have uncovered that linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in pathogen-mediated lung inflammation.

p-Synephrine suppresses lipopolysaccharide-induced acute lung injury by inhibition of the NF-κB signaling pathway.

OBJECTIVE: We investigated whether p-synephrine exerts potent anti-inflammatory effects against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo, and we further investigated the inhibitory mechanism of p-synephrine in LPS-induced ALI. METHODS: Lipopolysaccharide (0.5 mg/kg) was instilled intranasally in phosphate-buffered saline to induce acute lung injury, and 6, 24, and 48 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator. We also evaluated the effects of p-synephrine on LPS-induced the severity of pulmonary injury. The phosphorylation of nuclear factor-κB (NF-κB) p65 protein was analyzed by Western blotting. RESULTS: Our data showed that p-synephrine significantly reduced the amount of inflammatory cells, the lung wet-to-dry weight (W/D) ratio, reactive oxygen species, myeloperoxidase activity and enhanced superoxide dismutase (SOD) in mice with LPS-induced ALI. Tumor necrosis factor α and interleukin (IL)-6 concentrations decreased significantly while the concentration of IL-10 was significantly increased after p-synephrine pretreatment. In addition, p-synephrine suppressed not only the phosphorylation of NF-κB but also the degradation of its inhibitor (IκBα). CONCLUSIONS: These results suggested that the inhibition of NF-κB activation and the regulation of SOD are involved in the mechanism of p-synephrine's protection against ALI.

Protection of mice against lipopolysaccharide-induced endotoxic shock by pinocembrin is correlated with regulation of cytokine secretion.

Natural products have been used as potentially important sources of anti-inflammatory drugs. This study examined the effects of pinocembrin against lipopolysaccharide (LPS)-induced endotoxemia to ascertain whether pinocembrin could protect mice from ensuing death. Cytokine responses were also assessed in serum isolated from blood collected at 0, 2, 4, 6, 8, and 24 h after LPS administration of the mice (with or without drug treatment). The results showed that there was a lower production of TNFα, IL-6, and IL-1ß in the serum of LPS-challenged mice that had been pre-treated with pinocembrin. In addition, pre-treatment with pinocembrin improved host survival against the LPS-induced lethal endotoxemia. These results suggest that this new flavonoid could potentially be a novel candidate for preventing development/mitigation progression of septic shock.

Inhibition of lung inflammatory responses by bornyl acetate is correlated with regulation of myeloperoxidase activity.

BACKGROUND: Bornyl acetate is a bicyclic monoterpene present in numerous conifer oils. In this study, we aimed at clarifying the potential anti-inflammatory function and mechanism of bornyl acetate by using lipopolysaccharide (LPS)-induced acute lung injury murine model and RAW 264.7 cells. MATERIALS AND METHODS: RAW 264.7 cells were pretreated with bornyl acetate 1 h before LPS stimulation and cell-free super supernatants were collected to measure cytokine concentrations. To induce acute lung injury, BALB/c mice were injected intranasally with LPS and treated with bornyl acetate 1 h before LPS stimulation. Seven hours after administration, the bronchoalveolar lavage fluid (BALF) was collected for measuring the cell count and cytokine production. We collected lungs for assaying wet-to-dry weight ratio, myeloperoxidase activity, and histologic changes. The extent of phosphorylation of mitogen-activated protein kinases and nuclear factor κB was detected by Western blot. RESULTS: Our results showed that bornyl acetate downregulated the levels of proinflammatory cytokines in vitro and in vivo; reduced the number of total cells, neutrophils, and macrophages in BALF; attenuated the histologic alterations in the lung; decreased the wet-to-dry weight ratio in BALF; and suppressed NF-kappa-B inhibitor alpha, extracellular regulated protein kinases, c-JunN-terminal kinase, p38 mitogen-activated protein kinase activation. CONCLUSIONS: These findings suggested that bornyl acetate may be developed as a preventive agent for lung inflammatory diseases.

Role of sortase A in the pathogenesis of Staphylococcus aureus-induced mastitis in mice.

Sortase A (SrtA), a transpeptidase, anchors surface proteins with an LPXTG-motif sorting signal to the cell envelope. To determine the role of SrtA in the pathogenesis of Staphylococcus aureus, we constructed a mutant strain, ∆SrtA, by genetic techniques and identified its functions in a S. aureus-induced mastitis mouse model. The histological and myeloperoxidase (MPO) level results showed that the ∆SrtA strain attenuated the inflammatory reaction in the mammary tissue of mice compared with wild-type S. aureus challenge. Additionally, the ELISA results showed that the ∆SrtA strain impaired the induction of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and the Western blot results showed that the mutant strain blocked the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) by attenuating the degradation and phosphorylation of signaling pathway molecules such as IκBα, p65 and p38. These results suggest that SrtA is a key virulence factor in the pathogenesis of S. aureus-induced mastitis in mice. It appears that the srtA mutant affected the attachment of S. aureus to host cells, thus attenuating the activation of the NF-κB and MAPK signaling pathways, which regulated the expression of pro-inflammatory cytokines and decreased the susceptibility to mastitis.

Tubeimoside-1 attenuates LPS-induced inflammation in RAW 264.7 macrophages and mouse models.

CONTEXT: Acute lung injury (ALI), characterized by severe hypoxemia, pulmonary edema and neutrophil accumulation in the lung, is a common clinical problem associated with significant morbidity and mortality in shock, sepsis, ischemia reperfusion, etc. OBJECTIVE: In this study, we aimed at investigating the protective effect of tubeimoside-1 (TBMS1) on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and a LPS-induced in vivo lung injury model. MATERIALS AND METHODS: We evaluated the effect of TBMS1 on LPS-induced production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß in the culture supernatants of RAW 264.7 cells by enzyme-linked immunosorbent assay. LPS (0.5 mg/kg) was instilled intranasally in phosphate-buffered saline to induce ALI, and the severity of pulmonary injury was evaluated 6 h after LPS challenge. RESULTS: TBMS1 significantly inhibited the production of the pro-inflammatory cytokines, TNF-α, IL-6 and IL-1ß in vitro and in vivo. Pretreatment with TBMS1 markedly attenuated the development of pulmonary edema, histological severities and inflammatory cells infiltration in mice with ALI. In addition, we further demonstrated that TBMS1 exerts an anti-inflammatory effect in vivo model of ALI through suppression of IκB activation and p38/extracellular signal-regulated kinase mitogen-activated protein kinases signaling in a dose-dependent manner. DISCUSSION AND CONCLUSION: Overall, our data suggest that TBMS1 inhibits inflammation both in vitro and in vivo, and may be a potential therapeutic candidate for the prevention of inflammatory diseases.

Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice.

Prime-O-glucosylcimifugin is an active chromone isolated from Saposhnikovia root which has been reported to have various activities, such as anti-convulsant, anticancer, anti-inflammatory properties. The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. BALB/c mice received intraperitoneal injection of Prime-O-glucosylcimifugin 1h before intranasal instillation (i.n.) of lipopolysaccharide (LPS). Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary histological changes were evaluated by hematoxylin-eosin, myeloperoxidase (MPO) activity in the lung tissue and lung wet/dry weight ratios were observed. Furthermore, the mitogen-activated protein kinases (MAPK) signaling pathway activation and the phosphorylation of IκBα protein were determined by Western blot analysis. Prime-O-glucosylcimifugin showed promising anti-inflammatory effect by inhibiting the activation of MAPK and NF-κB signaling pathway.

Preventive effect of Imperatorin on acute lung injury induced by lipopolysaccharide in mice.

Imperatorin, a linear furanocoumarin, has many pharmacological effects such as antibacterial, anti-inflammatory and antiviral effects. The purpose of this study was to investigate the effect of Imperatorin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. BALB/c mice were pretreated with Imperatorin 1h before LPS challenge. We found that the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) were decreased significantly, and the level of interleukin-10 (IL-10) was up-regulated 8h after Imperatorin treatment. Pretreatment with Imperatorin (15 or 30 mg/kg) decreased lung wet-to-dry weight (W/D) ratio, the number of inflammatory cells and myeloperoxidase (MPO) activities. Additionally, Imperatorin attenuated lung histopathological changes and significantly inhibited the phosphorylation of IκB, JNK, ERK and p38/MAPK. These findings demonstrate that Imperatorin protects against LPS-induced ALI in mice.

p-Cymene protects mice against lipopolysaccharide-induced acute lung injury by inhibiting inflammatory cell activation.

The objective of this study was to test the hypothesis that p-cymene can attenuate acute lung injury induced by lipopolysaccharide (LPS) in vivo. In the mouse model of LPS-induced acute lung injury, intraperitoneal preconditioning with p-cymene resulted in a significant reduction of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), lung water gain, inflammatory cell infiltration, lung tissue myeloperoxidase activity. In addition, p-cymene blocked the phosphorylation of IκBα protein and mitogen-activated protein kinases (MAPK) signaling pathway activation. Histopathologic examination of lung tissue indicated that p-cymene treatment markedly decreased focal thickening, congestion, pulmonary edema, and inflammatory cells infiltration. The results showed that p-cymene had a protective effect on LPS-induced ALI in mice.