Antibacterial and antibiofilm efficacy of green synthesized ZnO nanoparticles using Saraca asoca leaves.

Biofilms are made up of bacterial colonies and their extracellular polymeric substances (EPS) matrix, which protects the bacteria from adverse environmental conditions. The increasing drug resistivity of pathogenic bacteria is becoming an emergency for developing new antibacterial agents. In this study, we have synthesized the zinc oxide nanoparticles (ZnO NPs) using the leaf extract of Saraca asoca plant, and the antibacterial and antibiofilm activity of green synthesized ZnO NPs was measured against the biofilm-producing bacteria Bacillus subtilis. The disk diffusion data reveals that the zone of inhibition (ZOI) starts at a concentration of 0.5 mg/mL and minimum inhibition concentration (100 µg/mL) and minimum bactericidal concentration (150 µg/mL) values were also evaluated for green synthesized ZnO nanomaterials. Crystal violet test and microscopic examination were used to assess the impact of produced nanoparticles on biofilm development. The findings indicated a nearly 45%, 64%, and 83% suppression of biofilm development at 0.5 × MIC, 0.75 × MIC, and 1 × MIC value, respectively. The biofilm biomass of the preformed or matured biofilms by the ZnO NPs was evaluated to be 68%, 50%, and 33% at concentrations of 0.5 × MIC, 0.75 × MIC, and 1 × MIC which was concentration-dependent. Moreover, flow cytometry results suggest damage to the bacterial cell membrane. The data indicated that the proportion of dead cells increased with NP concentration in comparison to the control. Therefore, it can be concluded that the green synthetic ZnO nanoparticles showed excellent antibacterial and antibiofilm activity against the Bacillus subtilis bacteria that produce biofilms and that they could be a promising substitute agent for the treatment of biofilms and drug-resistant bacteria.

Assessment of airline industry using a new double-frontier cross-efficiency method based on prospect theory.

Cross-efficiency method (CEM) is a well-known technique based on data envelopment analysis that provides policymakers with a powerful tool to measure the efficiency of decision-making units. However, there are two main gaps in the traditional CEM. First, it neglects the subjective preferences of decision-makers (DMs), and therefore, cannot reflect the importance of self-evaluation compared to peer-evaluations. Second, it ignores the importance of anti-efficient frontier in the overall evaluation. The present study aims to incorporate the prospect theory into the double-frontier CEM to deal with these drawbacks while considering the preferences of DMs towards gains and losses. To address these drawbacks, this paper utilizes an aggregation method based on the prospect theory and consensus degree (APC) to reflect the subjective preferences of DMs. The second issue is also addressed by incorporating APC into the optimistic and pessimistic CEMs. Finally, the double-frontier CEM aggregated using APC (DAPC) is obtained by aggregating two viewpoints. As a real case study, DAPC is applied to evaluate the performance of 17 Iranian airlines based on three inputs and four outputs. The findings demonstrate that both viewpoints are influenced by DMs' preferences. The ranking results achieved for more than half of the airlines based on the two viewpoints are significantly different. The findings confirm that DAPC deals with these differences and leads to more comprehensive ranking results by considering both subjective viewpoints simultaneously. The results also show that to what extent DAPC efficiency for each airline is influenced by each viewpoint. In this regard, the efficiency of IRA is most influenced by the optimistic point of view (80.92%), and on the other hand, the efficiency of IRZ is most influenced by the pessimistic viewpoint (73.45%). KIS is the most efficient airline, followed by PYA. On the other hand, IRA is the least efficient airline, followed by IRC.

Assessment of coal supply chain under carbon trade policy by extended exergy accounting method.

Within an uncertain environment and following carbon trade policies, this study uses the Extended Exergy Accounting (EEA) method for coal supply chains (SCs) in eight of the world's most significant coal consuming countries. The purpose is to improve the sustainability of coal SCs in terms of Joules rather than money while considering economic, environmental, and social aspects. This model is a multi-product economic production quantity (EPQ) with a single-vendor multi-buyer with shortage as a backorder. Within the SC, there are some real constraints, such as inventory turnover ratio, waste disposal to the environment, carbon dioxide emissions, and available budgets for customers. For optimization purposes, three recent metaheuristic algorithms, including Ant Lion Optimizer, Lion Optimization Algorithm, and Whale Optimization Algorithm, are suggested to determine a near-optimum solution to an "exergy fuzzy nonlinear integer-programming (EFNIP)." Moreover, an exact method (GAMS) is employed to validate the results of the suggested algorithms. Additionally, sensitivity analyses with different percentages of exergy parameters, such as capital, labor, and environmental remediation, are done to gain a deeper understanding of sustainability improvement in coal SCs. The results showed that sustainable coal SC in the USA has the lowest fuzzy total exergy, while Poland and China have the highest.

Carbon Nano-Onion-Decorated ZnO Composite-Based Enzyme-Less Electrochemical Biosensing Approach for Glucose.

This study investigates the enzyme-less biosensing property of the zinc oxide/carbon nano-onion (ZnO/CNO) nanocomposite coated on a glassy carbon electrode. The ZnO/CNO nanocomposite was synthesized using the ex situ mixing method, and the structural characterization was done using XRD, SEM, and TEM, whereas functional groups and optical characterization were done through FTIR and UV-visible spectroscopy. The electrochemical sensing response of the ZnO/CNO nanocomposite for the linear range of glucose concentration (0.1-15 mM) was examined using cyclic voltammetry (CV) with a potential window of -1.6 to +1.6 V using 0.1 M NaOH as an electrolyte. The ZnO/CNO nanocomposites showed enhanced sensing ability toward glucose with a sensitive value of 606.64 µA/mM cm2. Amperometric i-t measurement supports the finding of CV measurement and showed good sensing ability of the electrode ZnO/CNO nanocomposite material for up to 40 days. The enhanced electrocatalytic activity of the ZnO/CNO nanocomposite is explained due to the synergetic effect of both ZnO and CNO. Our findings suggest a high potential for ZnO/CNO nanocomposite-based glucose biosensors, which could be further utilized to develop noninvasive skin-attached sensors for biomedical applications.

Tracking Mitochondrial Density and Positioning along a Growing Neuronal Process in Individual C. elegans Neuron Using a Long-Term Growth and Imaging Microfluidic Device.

The long cellular architecture of neurons requires regulation in part through transport and anchoring events to distribute intracellular organelles. During development, cellular and subcellular events such as organelle additions and their recruitment at specific sites on the growing axons occur over different time scales and often show interanimal variability thus making it difficult to identify specific phenomena in population averages. To measure the variability in subcellular events such as organelle positions, we developed a microfluidic device to feed and immobilize Caenorhabditis elegans for high-resolution imaging over several days. The microfluidic device enabled long-term imaging of individual animals and allowed us to investigate organelle density using mitochondria as a testbed in a growing neuronal process in vivo Subcellular imaging of an individual neuron in multiple animals, over 36 h in our microfluidic device, shows the addition of new mitochondria along the neuronal process and an increase in the accumulation of synaptic vesicles (SVs) at synapses. Long-term imaging of individual C. elegans touch receptor neurons (TRNs) shows that the addition of new mitochondria takes place along the entire neuronal process length at a rate of ∼0.6 mitochondria/h. The threshold for the addition of a new mitochondrion occurs when the average separation between the two preexisting mitochondria exceeds 24 µm. Our assay provides a new opportunity to move beyond simple observations obtained from in vitro assays to allow the discovery of genes that regulate positioning of mitochondria in neurons.

Removal of reactive orange 16 and reactive green 19 using Cyphos IL101-impregnated Amberlite XAD7HP resin in batch and recirculating stirrer vessel.

Reactive dyes are highly soluble in water, and carcinogenic. Therefore, it is essential to remove these dyes from their aqueous solutions. This study focused on the simultaneous removal of reactive orange 16 (RO) and reactive green 19 (RG) dyes from their binary dye solution using Cyphos IL101-impregnated Amberlite XAD7HP resin (ILX7) in batch and recirculating stirrer vessel (RSV). In the batch study, the experimental operating conditions were designed by using central composite design of response surface methodology. Influence of important input variables (RO dye concentration, RG dye concentration, pH, and resin dosage) on the dye adsorption was studied and their values were optimized. At the optimum values of input variables, equilibrium, kinetic, and thermodynamic studies were performed for the binary dye mixture. The equilibrium and kinetic adsorption data were best fitted with extended-Freundlich and pseudo-second-order models, respectively. Now to intensify the process, continuous studies were performed in a RSV at optimum conditions and at different flow rates and stirring speeds. The impregnated resin was regenerated by using 80% v/v ethanol and successfully reused up to 3 cycles with slight decrease in the adsorption capacity.

Dose dependent enhanced antibacterial effects and reduced biofilm activity against Bacillus subtilis in presence of ZnO nanoparticles.

Bacterial biofilms are self-produced matrix of sticky extracellular polymeric substances. They result in fouling in the food industry, water treatment plants, and possess significant environmental and industrial impacts. Nanoparticles have shown immense potential and have been effective in combating bacterial biofilm, which is the common cause of drug resistance development, biofouling in water treatment plants and the food industry. Hence, in order to explore the same, Zinc oxide nanoparticles have been synthesized by chemical synthesis method and their action against Bacillus subtilis biofilm formation was evaluated in this study by crystal violet and ROS assay. The dose-dependent reduction in biofilm biomass and density was observed as a result of nanoparticle exposure. There was considerable reduction in biofilm formation after treatment with ZnO nanoparticles. Change in surface morphology of the Bacillus subtilis cells was observed which could be due to oxidative stress induced by ZnO nanoparticles. The oxidative stress was estimated by measurement of catalase activity that also showed dose-dependent decrease.

UNC-16/JIP3 and UNC-76/FEZ1 limit the density of mitochondria in C. elegans neurons by maintaining the balance of anterograde and retrograde mitochondrial transport.

We investigate the role of axonal transport in regulating neuronal mitochondrial density. We show that the density of mitochondria in the touch receptor neuron (TRN) of adult Caenorhabditis elegans is constant. Mitochondrial density and transport are controlled both by the Kinesin heavy chain and the Dynein-Dynactin complex. However, unlike in other models, the presence of mitochondria in C. elegans TRNs depends on a Kinesin light chain as well. Mutants in the three C. elegans miro genes do not alter mitochondrial density in the TRNs. Mutants in the Kinesin-1 associated proteins, UNC-16/JIP3 and UNC-76/FEZ1, show increased mitochondrial density and also have elevated levels of both the Kinesin Heavy and Light Chains in neurons. Genetic analyses suggest that, the increased mitochondrial density at the distal end of the neuronal process in unc-16 and unc-76 depends partly on Dynein. We observe a net anterograde bias in the ratio of anterograde to retrograde mitochondrial flux in the neuronal processes of unc-16 and unc-76, likely due to both increased Kinesin-1 and decreased Dynein in the neuronal processes. Our study shows that UNC-16 and UNC-76 indirectly limit mitochondrial density in the neuronal process by maintaining a balance in anterograde and retrograde mitochondrial axonal transport.

UNC-16/JIP3 regulates early events in synaptic vesicle protein trafficking via LRK-1/LRRK2 and AP complexes.

JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the µ-subunit of the AP-1 complex. AP1 regulates the size but not the composition of SVP transport carriers. Additionally, UNC-16 and LRK-1 through the AP-3 complex regulates the composition but not the size of the SVP transport carrier. These early biogenesis steps are essential for dependence on the synaptic vesicle motor, UNC-104 for axonal transport. Our results show that UNC-16 and its downstream effectors, LRK-1 and the AP complexes function at the Golgi and/or post-Golgi compartments to control early steps of SV biogenesis. The UNC-16 dependent steps of exclusion, inclusion and motor recruitment are critical for polarized distribution of neuronal cargo.

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.

Colored polydimethylsiloxane micropillar arrays for high throughput measurements of forces applied by genetic model organisms.

Measuring forces applied by multi-cellular organisms is valuable in investigating biomechanics of their locomotion. Several technologies have been developed to measure such forces, for example, strain gauges, micro-machined sensors, and calibrated cantilevers. We introduce an innovative combination of techniques as a high throughput screening tool to assess forces applied by multiple genetic model organisms. First, we fabricated colored Polydimethylsiloxane (PDMS) micropillars where the color enhances contrast making it easier to detect and track pillar displacement driven by the organism. Second, we developed a semi-automated graphical user interface to analyze the images for pillar displacement, thus reducing the analysis time for each animal to minutes. The addition of color reduced the Young's modulus of PDMS. Therefore, the dye-PDMS composite was characterized using Yeoh's hyperelastic model and the pillars were calibrated using a silicon based force sensor. We used our device to measure forces exerted by wild type and mutant Caenorhabditis elegans moving on an agarose surface. Wild type C. elegans exert an average force of ∼1 µN on an individual pillar and a total average force of ∼7.68 µN. We show that the middle of C. elegans exerts more force than its extremities. We find that C. elegans mutants with defective body wall muscles apply significantly lower force on individual pillars, while mutants defective in sensing externally applied mechanical forces still apply the same average force per pillar compared to wild type animals. Average forces applied per pillar are independent of the length, diameter, or cuticle stiffness of the animal. We also used the device to measure, for the first time, forces applied by Drosophila melanogaster larvae. Peristaltic waves occurred at 0.4 Hz applying an average force of ∼1.58 µN on a single pillar. Our colored microfluidic device along with its displacement tracking software allows us to measure forces applied by multiple model organisms that crawl or slither to travel through their environment.

Silymarin extends lifespan and reduces proteotoxicity in C. elegans Alzheimer's model.

Aging is a process of progressive decline in physiological functions resulting in increased vulnerability to diseases and death. Aging results in increased rates of age related disorders like neurodegenerative diseases, cardiovascular diseases, diabetes, cancer, arthritis etc. Modulation of insulin signaling, protein aggregation, stress, free radical damage and inflammation are the major causes for deleterious changes resulting in aging. Many studies are being undertaken to find novel compounds which can improve a typical human life span and aid in healthy aging. We investigated the potential of one such compound silymarin for its anti-aging effect. Silymarin is a flavanone derivative extracted from the seeds of the milk thistle Silybum marianum. It is widely used for the treatment of liver diseases in clinical practice. We tested the anti-aging efficacy of silymarin using the Caenorhabditis elegans model system. Our results demonstrate that C. elegans treated with 25µM and 50µM silymarin concentration resulted in an increase in mean lifespan by 10.1% and 24.8% respectively compared to untreated control. Besides increased lifespan, silymarin treated aged animals showed better locomotion rate, higher response to stimuli and improved tolerance to stress compared to untreated control. We also checked the potential of silymarin to slow the progression of neurodegenerative disorder like Alzheimer's disease (AD) by using CL4176 C. elegans model for AD. C. elegans CL4176 transgenic animal induces expression of amyloid beta-protein (Aß1-42) in muscle tissues when subjected to temperature of 23°C and above resulting in worm paralysis. CL4176 animals treated with silymarin showed delayed paralysis via enhancing resistance to oxidative stress. These results suggested that silymarin is a potential hormetin for preventing aging and age-related diseases.

Phycoerythrin extends life span and health span of Caenorhabditis elegans.

In the present study, we tested the antioxidant activity of phycoerythrin (PE, an oligomeric light harvesting protein isolated from Lyngbya sp. A09DM) to curtail aging effects in Caenorhabditis elegans. Purified PE (100 µg/ml) dietary supplement was given to C. elegans and investigated for its anti-aging potential. PE treatment improved the mean life span of wild type (N2)-animals from 15 ± 0.1 to 19.9 ± 0.3 days. PE treatment also moderated the decline in aging-associated physiological functions like pharyngeal pumping and locomotion with increasing age of N2 worms. Moreover, PE treatment also enhanced the stress tolerance in 5-day-aged adults with increase in mean survival rate from 22.2 ± 2.5 to 41.6 ± 2.5% under thermo stress and from 30.1 ± 3.2 to 63.1 ± 6.4% under oxidative (hydrogen peroxide)-stress. PE treatment was also noted to moderate the heat-induced expression of human amyloid-beta(Aß1-42) peptide and associated paralysis in the muscle tissues of transgenic C. elegans CL4176 (Alzheimer's disease model). Effectiveness of PE in expanding the life span of mutant C. elegans, knockout for some up (daf-2 and age-1)- and down (daf-16)-stream regulators of insulin/IGF-1 signaling (IIS), shows the independency of PE effect from DAF-2-AGE-1-DAF-16 signaling pathway. Moreover, the inability of PE in expanding the life span of hsf-1 knockout C. elegans(sy441) suggests the dependency of PE effect on heat shock transcription factor (HSF-1) controlling stress-induced gene expression. In conclusion, our results demonstrated a novel anti-aging activity of PE which conferred increased resistance to cellular stress resulting in improved life span and health span of C. elegans.

Using operations research to plan improvement of the transport of critically ill patients.

OBJECTIVE: Operations research is the application of mathematical modeling, statistical analysis, and mathematical optimization to understand and improve processes in organizations. The objective of this study was to illustrate how the methods of operations research can be used to identify opportunities to reduce the absolute value and variability of interfacility transport intervals for critically ill patients. METHODS: After linking data from two patient transport organizations in British Columbia, Canada, for all critical care transports during the calendar year 2006, the steps for transfer of critically ill patients were tabulated into a series of time intervals. Statistical modeling, root-cause analysis, Monte Carlo simulation, and sensitivity analysis were used to test the effect of changes in component intervals on overall duration and variation of transport times. Based on quality improvement principles, we focused on reducing the 75th percentile and standard deviation of these intervals. RESULTS: We analyzed a total of 3808 ground and air transports. Constraining time spent by transport personnel at sending and receiving hospitals was projected to reduce the total time taken by 33 minutes with as much as a 20% reduction in standard deviation of these transport intervals in 75% of ground transfers. Enforcing a policy of requiring acceptance of patients who have life- or limb-threatening conditions or organ failure was projected to reduce the standard deviation of air transport time by 63 minutes and the standard deviation of ground transport time by 68 minutes. CONCLUSIONS: Based on findings from our analyses, we developed recommendations for technology renovation, personnel training, system improvement, and policy enforcement. Use of the tools of operations research identifies opportunities for improvement in a complex system of critical care transport.

Multi walled carbon nano tubes induced hepatotoxicity in Swiss albino mice.

In the present study, multi walled carbon nano tubes (MWCNTs) were synthesized using chemical vapour deposition (CVD) technique. Swiss albino mice were orally administered with single dose of 60 and 100 mg/kg body weight of purified and functionalized MWCNTs suspended in water. The mice were autopsied on 7, 14, 21 and 28 days post exposure. Liver was taken out and part of it fixed in Bouin's solution for histopathological examinations. The remaining part was immersed in cold saline, blotted dry, weighed quickly and homogenized in ice cold buffer. The activity of superoxide dismutase (SOD) and catalase (CAT) was immediately measured in the supernatant. The MWCNTs in liver led to pathological changes, including injury to macrophages, cellular swelling, unspecific inflammation, spot necrosis and blood coagulation. Estimation of SOD and CAT showed altered levels in the experimental groups as compared to controls. Therefore, MWCNTs from manufactured and combustion sources in the environment can have adverse effects on human health.

Development of multiple embryos in polyembryonic insertional mutant OsPE of rice.

A T-DNA insertional mutant OsPE of rice gives twin and triplet seedlings in up to 20 % of the seeds. Detailed cytological and histological analysis of OsPE indicated normal male and female gametogenesis in the OsPE mutant. Confocal laser scanning microscopic (CLSM) analysis of the developing seeds of OsPE showed multiple embryo development in up to 60 % of the ovules. The multiple embryos, mostly twins and triplets, and rarely quadruplets, developed through sequential cleavage from a single zygotic embryo in each ovule. The reduced number of multiple seedlings compared with multiple embryos observed in CLSM study may be attributed to their inability to develop further due to competition in a single embryo sac. Key message Multiple seedlings in the OsPE mutant are due to sequential proliferation and cleavage of the zygotic embryos. The nucellar tissue was not involved in multiple embryo development.

Reduced tillering in Basmati rice T-DNA insertional mutant OsTEF1 associates with differential expression of stress related genes and transcription factors.

A T-DNA insertional mutant OsTEF1 of rice gives 60-80% reduced tillering, retarded growth of seminal roots, and sensitivity to salt stress compared to wild type Basmati 370. The insertion occurred in a gene encoding a transcription elongation factor homologous to yeast elf1, on chromosome 2 of rice. Detailed transcriptomic profiling of OsTEF1 revealed that mutation in the transcription elongation factor differentially regulates the expression of more than 100 genes with known function and finely regulates tillering process in rice by inducing the expression of cytochrome P450. Along with different transcription factors, several stress associated genes were also affected due to a single insertion. In silico analysis of the TEF1 protein showed high conservation among different organisms. This transcription elongation factor predicted to interact with other proteins that directly or indirectly positively regulate tillering in rice.

Abnormal endosperm development causes female sterility in rice insertional mutant OsAPC6.

A T-DNA insertional mutant OsAPC6 of rice, with gibberellic acid insensitivity and reduced height, had up to 45% reduced seed set. The insertion occurred on chromosome 3 of rice in the gene encoding one of the subunits of anaphase promoting complex/Cyclosome APC6. The primary mother cells of the mutant plants had normal meiosis, male gametophyte development and pollen viability. Confocal laser scanning microscopic (CLSM) studies of megagametophyte development showed abnormal mitotic divisions with reduced number or total absence of polar nuclei in about 30-35% megagametophytes of OsAPC6 mutant leading to failure of endosperm and hence embryo and seed development. Abnormal female gametophyte development, high sterility and segregation of tall and gibberellic acid sensitive plants without selectable marker Hpt in the selfed progeny of OsAPC6 mutant plants indicate that the mutant could be maintained in heterozygous condition. The abnormal mitotic divisions during megagametogenesis could be attributed to the inactivation of the APC6/CDC16 of anaphase promoting complex of rice responsible for cell cycle progression during megagametogenesis. Functional validation of the candidate gene through transcriptome profiling and RNAi is in progress.

Status of Stat3 in an ovalbumin-induced mouse model of asthma: analysis of the role of Socs3 and IL-6.

BACKGROUND: Stat3, Socs3 and cytokines play an integral role in the coordination and persistence of inflammation. However, a clear understanding of the role played by the Stat3/IL-6 and Socs3 pathway in airway inflammation is lacking. We report the alteration in the status of expression and activation of Stat3 by ovalbumin (OVA), and establish its relationship with Socs3 and IL-6 in the lungs of mice with eosinophilic pulmonary inflammation and airway hyperresponsiveness. METHODS: Alterations in the expression of Stat3, Socs3 and IL-6 were determined in a murine model of asthma, where Balb/c mice were sensitized and challenged with OVA (OVA/OVA) and compared with control mice sensitized and challenged with saline (SAL) (SAL/SAL) mice. The OVA/OVA mice were characterized by a moderate increase in methacholine-induced specific airway resistance, the presence of 150 microg/ml of OVA-specific IgG and 8.93 microg/ml OVA-specific IgE antibody and elevated levels of eosinophils and Th2 cytokines (IL-4 and IL-5) in the bronchoalveolar lavage fluid. In contrast SAL/SAL mice had low eosinophils, IL-4 and IL-5 and no OVA-specific IgG and IgE antibodies in the BALF. Stat3 and Socs3 expression profiles were monitored in OVA/OVA and Stat3- and Socs3-silenced OVA/OVA mice. Furthermore, expression of IL-6 in Stat3- and Socs3-silenced mice and the exogenous effect of IL-6 on Stat3 were studied. RESULTS: The results show that expression and activation of Stat3 mRNA and proteins are significantly low in lung of OVA/OVA mice in comparison to SAL/SAL mice following OVA challenge. An increased pool of Socs3 mRNA is observed in OVA/OVA mice with or without OVA challenge and in SAL/SAL mice 24 h after OVA challenge. Transient in vivo blocking of Socs3 gene by Socs3 siRNA restores the expression of IL-6 mRNA and protein in OVA/OVA mice, and nasal administration of recombinant IL-6 to OVA/OVA mice enhanced Stat3 mRNA expression. CONCLUSIONS: Our data suggest that airway inflammation is associated with low expression of Stat3 and IL-6 and overexpression of Socs3 genes in a mouse model of asthma. Furthermore, IL-6 is under the influence of the Socs3 gene and may contribute to the negative regulation of Stat3 via IL-6 following a challenge with an allergen during the development of asthma.