Evaluation comparative de l'activité anti-oxydante des extraits éthanoliques des feuilles d'Olea europaea L. de l'Est Algérien / Comparative evaluation of antioxidant activity of ethanolic extracts from leaves of Olea europaea L. from Eastern Algeria

Introduction: Objectif-Dans les dernières décennies il y a eu un intérêt croissant pour l'étude des plantes médicinales et leur utilisation traditionnelle pour le traitement de diverses maladies. L'olivier ou Olea europaea L. constitue une entité indissociable des peuples méditerranéens. Cette plante appartient à la grande famille des oleaceae. L'objectif de cette étude a été d'évaluer l'activité anti-oxydante des extraits éthanoliques de quatre variétés sauvages de la plante O.europaea des régions de l'Est algérien : Batna et Mila (hautes-plateaux), Biskra (Sahara) et Skikda (ville côtière). Matériels et méthodes - L'évaluation de l'activité anti-oxydante in vitro des extraits éthanoliques de la plante O.europaea a été réalisée par différentes méthodes, notamment le piégeage du radical libre DPPH• et le pouvoir réducteur des ions ferriques. Résultats : L'analyse quantitative des extraits éthanoliques des feuilles de la plante O.europaea a révélé que l'extrait de Mila était plus riche (420.36 mg GAE/g MS), suivi de celui de Batna (396.84 mg GAE/g MS), puis celui de Biskra (de 380.69 mg GAE/g MS) et enfin de l'extrait de Skikda (368.45 mg GAE/g MS). Les résultats de l'activité antiradicalaire des extraits éthanoliques ont montré que ceux de Batna et Mila possédaient le pouvoir le plus important. Conclusion -Les résultats obtenus confirment favorablement l'utilisation des feuilles d'O.europaea en médecine traditionnelle algérienne pour le traitement de diverses maladies.

Introduction-Objective-In recent decades the study of medicinal proprieties of Olea europaea showed an increase interest of medicinal plants and their traditional use for the treatment of various diseases. The olive tree or Olea europaea L. is an inseparable entity of the Mediterranean people. This plant belongs to the large family of oleaceae. The purpose of this study was to assess the antioxidant activity of the ethanolic extracts from four wild varieties of O.europea in the eastern regions of Algeria: Batna and Mila (highlands), Biskra (Sahara) and Skikda (coastal city). Material and methods - The evaluation of the antioxidant activity in vitro of the ethanolic extracts of O.europaea plant was carried out by various methods, in particular, 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging effect and ferric reducing antioxidant power (FRAP). Results -Quantitative analysis of ethanolic extracts from the leaves of the plant O.europaea revealed that Mila's extract was richer (420.36 mg GAE / g DM), followed by that of Batna (396.84 mg GAE / g DM), then that of Biskra (380.69 mg GAE / g MS) and finally by Skikda extract (368.45 mg GAE / g MS). The results of DPPH free radical scavenging of the ethanolic extracts showed that those of Batna and Mila had the most important power. Conclusion - The obtained results favorably confirm the use of O.europaea leaves in traditional Algerian medicine for the treatment of various diseases.

Cloning and expression analysis of three critical triterpenoid pathway genes in Osmanthus fragrans

Background: Osmanthus fragrans is an important ornamental tree and has been widely planted in China because of its pleasant aroma, which is mainly due to terpenes. The monoterpenoid and sesquiterpenoid metabolic pathways of sweet osmanthus have been well studied. However, these studies were mainly focused on volatile small molecule compounds. The molecular regulation mechanism of synthesis of large molecule compounds (triterpenoids) remains unclear. Squalene synthase (SQS), squalene epoxidase (SQE), and beta-amyrin synthase (BETA-AS) are three critical enzymes of the triterpenoid biosynthesis pathway. Results: In this study, the full-length cDNA and gDNA sequences of OfSQS, OfSQE, and OfBETA-AS were isolated from sweet osmanthus. Phylogenetic analysis suggested that OfSQS and OfSQE had the closest relationship with Sesamum indicum, and OfBETA-AS sequence shared the highest similarity of 99% with that of Olea europaea. The qRT-PCR analysis revealed that the three genes were highly expressed in flowers, especially OfSQE and OfBETA-AS, which were predominantly expressed in the flowers of both "Boye" and "Rixiang" cultivars, suggesting that they might play important roles in the accumulation of triterpenoids in flowers of O. fragrans. Furthermore, the expression of OfBETA-AS in the two cultivars was significantly different during all the five flowering stages; this suggested that OfBETA-AS may be the critical gene for the differences in the accumulation of triterpenoids. Conclusion: The evidence indicates that OfBETA-AS could be the key gene in the triterpenoid synthesis pathway, and it could also be used as a critical gene resource in the synthesis of essential oils by using bioengineered bacteria.

Cytotoxic Triterpenoids from the Fruits of Ligustrum japonicum

Medicinal plants are potential sources of anticancer agents screening. A large number of phytochemicals, including triterpenoids, have been reported to have significant cytotoxic effects on cancer cells. From the fruits of Ligustrum japonicum Thunb., thirteen triterpenoids (1 – 13) were isolated and evaluated for their cytotoxic activity against Hela and HL-60 cells. As results, 8 (oleanolic acid) showed significant effects on Hela with IC50 values of 5.5 µM, and moderate effects on HL-60 cells with IC₅₀ values of 55.9 µM. Meanwhile, 10 (oleanderic acid) and 11 (3β-acetoxy-urs-12-en-28-oic acid) exhibited moderate inhibitory effects on Hela with IC₅₀ value of 55.0 and 68.8 µM, respectively. Moreover, 10 showed cytotoxic effect on HL-60 cell line with IC₅₀ value of 63.9 µM. To our knowledge, this is the first report that oleanderic acid was isolated from L. japonicum and investigated in cytotoxic effects on Hela and HL-60 cells.

Chemical constituents of Osmanthus fragrans / 中国中药杂志

By Silica gel, Sephadex LH-20 and other materials for isolation and purification and by physicochemical methods and spectral analysis for structural identification, 32 compounds were isolated and identified from ethyl acetate portion of alcohol extract of the Osmanthus fragrans. Their structures were identified as boschniakinic acid (1), ursolaldehyde (2), augustic acid (3), arjunolic acid (4), 5-hydroxymethyl-2-furancarboxaldehyde (5), isoscutellarein (6), 6, 7-dihydroxycoumarin (7), 2α-hydroxy-oleanolic acid (8), quercetin-3-0-β-D-glu-copyranoside (9), D-allito (10), 5, 4'-dihydroxy-7- methoxyflavone-3-0-β-D-glucopyranoside (11), 5,7-dihydroxychromone (12), lupeol (13), naringenin (14), acetyloleanolic acid (15), chlorogenic acid (16), kaempferol-3-0-β- D-glucopyranoside (17), oleanolic acid (18), kaempferol-3-0-β-D-galactopyanoside (19), 3', 7-dihydroxy-4'-methoxyisoflavon (20), ergosta-4,6,8 (14), 22-tetraen-3-one (21), p-hydroxycinnamic acid (22), syringaresinol (23), 3,4-dihydroxyacetophenonel (24), β-sitosterol (25), ethyl p-hydroxyphenylacetate (26), benzoic acid (27), caffeic acid (28), coelonin (29), p-hydorxy-phenylacetic acid (30), p-hydroxyacetophenone (31), and methyl-p-hydroxphenylacetate (32). Except for compounds 2, 4, 5, 8-11, 13, 15, 18, 20, 25, and 27, the rest were isolated from the Osmanthus fragrans for the first time.

Anti-cancer Activity of Osmanthus matsumuranus Extract by Inducing G2/M Arrest and Apoptosis in Human Hepatocellular Carcinoma Hep G2 Cells

BACKGROUND: Osmanthus matsumuranus, a species of Oleaceae, is found in East Asia and Southeast Asia. The bioactivities of O. matsumuranus have not yet been fully understood. Here, we studied on the molecular mechanisms underlying anti-cancer effect of ethanol extract of O. matsumuranus (EEOM). METHODS: Inhibitory effect of EEOM on cell growth and proliferation was determined by WST assay in various cancer cells. To investigate the mechanisms of EEOM-mediated cytotoxicity, HepG2 cells were treated with various concentration of EEOM and analyzed the cell cycle arrest and apoptosis induction by flow cytometry, Western blot analysis, 4,6-diamidino-2-phenylindole (DAPI) staining and DNA fragmentation. RESULTS: EEOM showed the cytotoxic activities in a dose-dependent manner in various cancer cell lines but not in normal cells, and HepG2 cells were most susceptible to EEOM-induced cytotoxicity. EEOM induced G2/M arrest in HepG2 cells associated with decreased expression of cyclin-dependent kinase 1 (CDK1), cyclin A and cylcin B, and increased expression of phospho-checkpoint kinase 2, p53 and CDK inhibitor p21. Immunofluorescence staining showed that EEOM-treated HepG2 increased doublet nuclei and condensed actin, resulting in cell rounding. Furthermore, EEOM-mediated apoptosis was determined by Annexin V staining, chromatin condensation and DNA fragmentation. EEOM caused upregulation of FAS and Bax, activation of caspase-3, -8, -9, and fragmentation of poly ADP ribose polymerase. CONCLUSIONS: These results suggest that EEOM efficiently inhibits proliferation of HepG2 cells by inducing both G2/M arrest and apoptosis via intrinsic and extrinsic pathways, and EEOM may be used as a cancer chemopreventive agent in the food or nutraceutical industry.

Free Radical Scavenging Activities of Nyctanthes arbor-tristis. L on Adjuvant Induced Arthritis in Rats.

Aims: The present study was undertaken to explore in vivo antioxidant potential of ethanol extracts of Nyctanthes arbor-tristis leaf and stem in adjuvant induced arthritic rats. Methodology: Arthritis induced rats were administered with extract of Nyctanthes arbortristis leaf and stem. (150 mg/kg body Weight/rat/day for 30 days. Results: A significant decrease in paw edema was observed following oral administration of the leaf and stem extracts. A significant (p<0.05) increase in the level of tissue TBARS, GPx and catalase was seen in arthritis induced rats (group II) and NAT treated rats (group III and group IV) showed a significant decrease in lipid peroxides, GPx and catalase level to near normalcy. The activity of total tissue SOD was found significantly (p<0.05) low in arthritis induced rats (group II) while a substantial increase in the activity to near normal level was noticed in NAT administered rats. The alterations in hematological and other biochemical parameters were restored to near normal levels after a treatment period of 30 days. The structural changes of the tissues shows the therapeutic ability of Nyctanthes arbor-tristis stem and leaf in experimental animals which were further evidenced by histological observations made on the hind limb tissue. Conclusion: As Nyctanthes arbor-tristis is of natural origin, it is a safe and effective intervention for free radical mediated diseases.

In vitro antioxidant evaluation and total phenolics of methanolic leaf extracts of Nyctanthes arbor-tristis L / 中国天然药物

AIM@#To investigate the in vitro antioxidant activity and total phenolic content of the methanolic leaf extract of Nyctanthes arbor-tristis L. (NA).@*METHODS@#The sample was tested using five in vitro antioxidant methods (1, 1-diphenyl-2-picryl hydrazine radical scavenging activity (DPPH), hydroxyl radical-scavenging activity (-OH), nitric oxide scavenging activity (NO), superoxide radical-scavenging activity, and total antioxidant activity) to evaluate the in vitro antioxidant potential of NA and the total phenolic content (Folin-Ciocalteu method). The extract showed good free radical scavenging property which was calculated as an IC50 value.@*RESULTS@#IC50 (Half maximal inhibitory concentration) of the methanolic extract was found to be 57.93 μg·mL(-1) for DPPH, 98.61 μg·mL(-1) for -OH, 91.74 μg·mL(-1) for NO, and 196.07 μg·mL(-1) for superoxide radical scavenging activity. Total antioxidant capacity of the extract was found to be (1198 ± 24.05) mg ascorbic acid for the methanolic extract. Free radical scavenging activity observed in the extracts of NA showed a concentration-dependent reaction. The in vitro scavenging tested for free radicals was reported to be due to high phenolic content in the leaf extract. The leaf extract of NA showed the highest total phenolic content with a value of 78.48 ± 4.2 equivalent mg TAE/g (tannic acid equivalent).@*CONCLUSIONS@#N. arbor-tristis leaf extract exhibited potent free radical scavenging activity. The finding suggests that N. arbor-tristis leaves could be a potential source of natural antioxidant.

Chemical constituents of Osmanthus fragrans fruits / 中国中药杂志

By Silica gel, Sephadex LH-20 and other materials for isolation and purification and by physicochemical methods and spectral analysis for structural identification, 23 compounds were isolated and identified from ethyl acetate portion of alcohol extract solution of Osmanthus fragrans fruits. Their structures were identified as nicotinamide (1), D-allitol (2), 5-hydroxymethyl-2-furancarboxaldehyde (3), acetyloleanolic acid (4), benzoic acid (5), ergosta-7,22-dien-3-one (6), beta-sitosterol (7), borreriagenin (8), cerevistero (9), c-veratroylglycol (10), methyl-2-O-beta-glucopyranosylbenzoate (11), 3', 7-dihydroxy-4'-methoxyisoflavon (12), umbelliferone (13), caffeic acid methyl ester (14), oleanolic acid (15), (-) -chicanine (16), dillapiol (17), 3beta,5alpha, 9alpha-trihydroxyergosta-7-22-dien-6-one (18), 2alpha-hydroxy-oleanolic acid (19), betulinic acid (20), betulin (21), 3, 3'-bisdemethylpinoresinol (22), and lupeol (23). All compounds were isolated from the osmanthus fruit for the first time. Except for compounds 4, 7, 15, 19, 23, the rest ones were isolated from the this plant for the first time.

Study on process conditions of Forsytiae Fructus / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of different processing methods on the content and biological activity of main chemical constituents of Forsytiae Fructus, in order to provide the basis for rational processing of Forsytiae Fructus.</p><p><b>METHOD</b>The content of extracts was determined by the extract determination method of Chinese Pharmacopoeia. The effects of chemical constituents of Forsytiae Fructus under different processing conditions were compared by HPLC method. Furthermore, free radical scavenging DPPH method was used to assess the antioxidation effect, and the antibacterial effect of Forsytiae Fructus was evaluated according to the inhibition effect on staphylococcus aureus.</p><p><b>RESULT</b>Considering various factors, the optimum boiling process is that adding six-fold water and boiling for 8 min.</p><p><b>CONCLUSION</b>The content and activity of chemical constituents of Forsytiae Fructus are significantly different under different processing conditions.</p>

Biochemical composition and germination capacity of Ligustrum lucidum ait. seeds in the process of biological invasion / Composição bioquímica e capacidade de germinação de sementes de Ligustrum lucidum ait. no processo de invasão biológica

Ligustrum lucidum ait. is an exotic species and In the present study, contents of sugars, proteins, and germination were evaluated in seeds removed from not abscisic and abscisic fruits. The seeds were stored or not under shadow or sun. The higher contents of total and reducing sugars were observed in seeds removed from not abscisic fruit while the period of storage resulted in the loss of these compounds. The same result was observed in the content of total sugars of seeds from abscisic fruits. The content of reducing sugars in seeds from abscisic fruits and submitted to storage had its content increased. The contents of total proteins in seeds from abscisic and not abscisic submitted to shadow or sun were not significantly different, but the results suggested an increase in protein synthesis during the storage period, differently from those seeds that were not submitted to storage. When seeds from abscisic and not abscisic fruits were evaluated immediately after harvest, they presented greater percentages of germination, while after 28 days, seeds submitted to the storage treatments showed lower values. The invasive potential of L. lucidum seems to be more associated to the number of seeds produced, than to their germination potential.

Ligustrum lucidum ait. é uma espécie exótica e no presente trabalho foram avaliados os teores de açúcares totais, redutores, proteínas, e germinação de sementes retiradas de frutos coletados da planta-mãe (não abscisados) e dispersos (abscisados) mantidos ou não em condições de sombra ou sol. Os maiores teores de açúcares totais e redutores foram obtidos em sementes imaturas, enquanto o armazenamento levou à perda destes composto, o que foi observado também para açúcares totais, nas mesmas condições, para sementes maduras. Verificaram-se aumentos nos teores de açúcares redutores em sementes maduras armazenadas. Apesar de não serem estatisticamente significativos, estes resultados entre sementes maduras e imaturas submetidas ao mesmo tratamento, indicam possível aumento da síntese protéica durante o período de armazenamento, sugerido pelo acréscimo no teor de proteínas totais, com pequena perda e/ou inibição em sementes de frutos submetidos ao sol. Sementes maduras e imaturas, imediatamente testadas após a coleta, apresentaram os maiores valores de porcentagem de germinação. no final de 28 dias de avaliação, enquanto aquelas submetidas aos tratamentos de armazenamento ficaram muito abaixo destes valores. Pelo presente trabalho, o potencial invasor de L. lucidum parece estar relacionado mais ao número de sementes produzidas pela espécie que o seu potencial germinativo.

Assessment of genetic diversity and relationships among osmanthus fragrans cultivars using AFLP markers

This study was conducted to reveal genetic diversity among 100 Osmanthus fragrans cultivars using amplified fragment length polymorphism (AFLP) markers. Eight AFLP primer combinations produced a total of 443 polymorphic fragments with an average of 64 per primer combination. The percentage of polymorphic bands (86.81 percent), the resolving power (Rp) (32.71) and the PIC values (0.331) showed the efficiency of used primer combinations. The revealed AFLP makers were effective in distinguishing all the cultivars considered. Cluster analysis were performed to assess patterns of diversity among cultivars and showed the abundant genetic diversity. The overall distribution pattern of molecular variation suggested that 93.33 percent of the total genetic variance was within the identified groups and 6.67 percent of the genetic variation was among the identified groups. Our results showed that AFLP markers are useful for Osmanthus fragrans germplasm discrimination as well as for investigation of genetic diversity and variation. The information will facilitate germplasm identification, conservation and new cultivar development.

Influence of ethanolic extract of Jasminum grandflorum linn flower on wound healing activity in rats.

The influence of flower extract of Jasminum grandiflorum was studied for its wound healing activity at a dose of 250 mg/kg body weight, using excision and dead space wound models in rats. The animals were divided into three groups in excision wound model, the controls (n=10) were treated with 0.25% CM cellulose, reference standard (n=10) were treated with sulfathiazole ointment and the experimental (n=10) were treated with extract of J. grandiflorum flower till complete epithelialization. The animals in dead space wound models were divided into two groups, controls were given plain drinking water and the experimental animals were administered with extract orally for 10 days. The extract treated wounds were found to epithelize faster as compared to controls. Extract-treated rats exhibited 65% reduction in the wound area when compared to controls (54%). The wet and dry granulation tissue weight, and hydroxyproline content in a dead space wound model increased significantly (P < 0.001) when compared to controls. Histological studies of the tissue obtained on day 10 from the extract-treated group showed increased well organized bands of collagen, more fibroblasts and few inflammatory cells when compared to controls which showed inflammatory cells, scanty collagen fibres and fibroblasts. The. demonstration of increased rate of wound contraction together with the biochemical and histological findings suggest the use of J. grandiflorum flower extract in the management of wound healing.

Studies on taste-masking technology of traditional Chinese medicine compounds / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the preparation of Shuanghuanglian taste-masking microspheres by spray-drying.</p><p><b>METHOD</b>Traced the compounds bitterness source, marked its curve and optimized the microspheres preparation by taking taste evaluation, microspheres yield and inclusion rate as the indexes.</p><p><b>RESULT</b>The bitter taste of compounds comes from Forsythia suspensa. The best taste-masking material is Eudragit E100. The optimal spray-drying parameters: solvent concentration 2.0%, inlet air temperature 75 degrees C, aspirator 35.0 m3 x h(-1), spray flow 0.35 m3 x h(-1), pump speed 8.0 mL x min(-1).</p><p><b>CONCLUSION</b>The spray-drying as a method of masking the traditional Chinese medicine compound taste have advantages of simple process and efficient masking.</p>

Comparative studies of different organs of Nyctanthes arbortristis in modulation of cytokines in murine model of arthritis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the modulation effect of pro- and anti-inflammatory cytokines following long term use of water soluble ethanol extracts from different organs of Nyctanthes arbortristis (NAT) in mouse model of arthritis.</p><p><b>METHODS</b>Arthritis was induced in mice by two injections of Freund's complete adjuvant on days 0 and 12 in the sub-planter surface of the right hind paw.</p><p><b>RESULTS</b>Injection of adjuvant resulted in a maximum primary edema of the footpad with erythema, and edema and distortion of joints of the right hind paw after 24-48 hours. Second injection of FCA led to the formation of secondary swellings persisting more than four weeks that spread onto the other hind limb but to a lesser extent. Histological analysis of the ankle on day 47 showed marked evidence of cartilage destruction in association with pannus formation and moderate bone resorption. Proinflammatory cytokine levels in the inflamed joint homogenate were elevated on days 2, 14, and 47. Oral administration of leaf and fruit extracts in arthritic mice reduced joint homogenate levels of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 on days 2, 14, and 47 in comparison to untreated arthritic mice. Interleukin-10 level was elevated in the inflamed joint on days 2, 14, and 47 in comparisons to untreated arthritic mice.</p><p><b>CONCLUSION</b>Evidence of lesser inflammation of the footpad and joint and associated histological observation support the therapeutic benefit of leaf and fruit extracts from Nyctanthes arbortristis. This study helps in understanding the mechanism of anti-inflammatory action of Nyctanthes arbortristis in the light of pro- and anti-inflammatory cytokine balance.</p>

Antiviral profile of Nyctanthes arbortristis L. against encephalitis causing viruses.

The ethanolic extracts, various fractions and two pure compounds isolated from the plant N. arbortris were tested against Encephalomyocarditis Virus (EMCV) and Semliki Forest Virus (SFV). Pronounced in vitro virus inhibitory activity was observed with the ethanolic and n-butanol fractions as well as with the pure compounds arbortristoside A and arbortristoside C. In addition, ethanolic extracts and n-butanol fraction protected EMCV infected mice to the extent of 40 and 60% respectively against SFV at a daily dose of 125 mg/kg body weight.

The effect of miswak and tooth brush filaments end-surface texture on enamel. A SEM pilot study.

OBJECTIVE: The aim of the study was to compare the abrasive effect of miswak and toothbrush filaments on enamel tooth surface. MATERIAL AND METHODS: Ten maxillary central incisors were obtained from Division of Maxillofacial Surgery, King Saud University, College of Dentistry. Twenty specimen were prepared, they were divided into 4 groups (1) Butler toothbrush; (2) Aquafresh toothbrush; (3) Miswak; (4) Control group. Miswak, Aquafresh 311 and Butler 311 tooth brush were used with light pressure in one direction motion for 60 seconds on enamel surface. The specimens were prepared for Scanning Electron Microscopy (SEM) examination. The middle filament from toothbrushes and miswak were also prepared for SEM. RESULTS: Showed that filaments end-surface texture play a major role in abrasive active activity and enamel tooth surface loss. CONCLUSION: The Butler 311 toothbrush and miswak showed lesser effect on enamel as compared to Aquafresh 311 toothbrush.

Silica induced early fibrogenic reaction in lung of mice ameliorated by Nyctanthes arbortristis extract / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles.</p><p><b>METHOD</b>Lung injury was induced in Swiss mice through inhalation exposure to silica particles (< 5 mu) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury.</p><p><b>RESULTS</b>Inhalation of silica increased the level of tumor necrosis factor-alpha (TNF-alpha), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-alpha in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung.</p><p><b>CONCLUSION</b>NAT leaf extract helps in bypassing silica induced initial lung injury in mice.</p>