Time dependent release of microplastics from disposable face masks poses cyto-genotoxic risks in Allium cepa.

The use of disposable face masks (DFMs) increased during the COVID-19 pandemic and has become a threat to the environment due to the release of microplastics (MPs). Although many reports have characterized and explored the release of MPs from DFMs and their effects in aquatic ecosystems, there is a lack of investigation into the effects in terrestrial plants. This report aims to fill this research gap by characterizing whole mask leachates (WMLs) collected at different time points and examining their toxicity on Allium cepa, a terrestrial model plant. Various analytical techniques including FE-SEM, FT-IR, and Raman spectroscopy were used to identify MPs in WMLs. The MPs are composed of polypropylene mostly and the concentration of smaller-sized MPs increased with leachate release time. The WMLs showed a MP concentration-dependent cytogenotoxic effect (72 %, 50 %, and 31 %, on 1, 5, and 11-day WMLs, respectively) on A. cepa root cells due to elevated oxidative stress (19 %, 45 %, and 70 %, on 1, 5, and 11-day WMLs, respectively). Heavy metal content of the WMLs was negligible and, thus, not a significant contributor to toxicity in the plant. Overall, this report highlights the fate of DFMs in the environment and their biological impacts in a model plant.

Antibacterial activity of a novel compound isolated from Bacillus licheniformis for treating bacterial infections in fishes: An in-silico approach.

Aeromonas hydrophila is a fish pathogen which is widely associated with diseases related to freshwater fishes. Vibrio parahemolyticus is a major globally emerging marine pathogen. Seven novel compounds were extracted from the ethyl acetate extract of Bacillus licheniformis, a novel marine bacterium isolated from marine actinomycetes. The compounds were identified using Gas Chromatography-Mass Spectroscopy (GC-MS). Only one bioactive compound having potent antibacterial activity was virtually screened to understand its drug-like property according to Lipinski's rule. The core proteins, 3L6E and 3RYL from the pathogens, A. hydrophila and V. parahemolyticus were targeted for drug discovery. In the present in-silico approach, Phenol,2,4-Bis(1,1-Dimethylethyl) a potent bioactive compound present in Bacillus licheniformis was used to prevent the infection due to the two pathogens. Further, using this bioactive compound, molecular docking was done to block their specific target proteins. This bioactive compound satisfied all the five rules of Lipinski. Molecular docking result revealed the best binding efficacy of Phenol,2,4-Bis(1,1-Dimethylethyl) against 3L6E and 3RYL with - 4.24 kcal/mol and - 4.82 kcal/mol, respectively. Molecular dynamics (MD) simulations were also executed to determine the binding modes as well as the stability of the protein-ligand docking complexes in the dynamic structure. The in vitro toxicity analysis of this potent bioactive compound against Artemia salina was carried out, revealing the non-toxic nature of B. licheniformis ethyl acetate extract. Thus, the bioactive compound of B. licheniformis was found to be a potent antibacterial agent against A. hydrophila and V. parahemolyticus.

A distribution-free procedure for testing versatile alternative in medical multisample comparison studies.

We propose a test for multisample comparison studies that can be applied without strict assumptions, especially when the underlying population distributions are far from normal. The new test can detect differences not only in location or scale but also in shape parameters among parent population distributions. We are motivated by numerous medical studies, where the variables are not normally distributed and may present in the various groups more complex differences than simple differences in a particular aspect of underlying distributions, such as location or scale. In these situations, traditional ANOVA and Kruskal-Wallis tests are unreliable since the underlying assumptions are not valid. The proposed procedure also allows the researcher to determine which aspects are more responsible for a significant result. This is an important practical advantage over procedures that test for general differences among the distribution functions but cannot identify which aspects lead to significant results. The asymptotic distribution of the test statistic is analyzed along with its small sample behavior against several competing tests. The practical advantages of the proposed procedure are illustrated with a multisample comparison study of a biomarker for liver damage in patients with hepatitis C.

Polystyrene nanoplastics diminish the toxic effects of Nano-TiO2 in marine algae Chlorella sp.

Widespread usage of nano-TiO2 in various commercial products and their consequent release into the seawater pose a severe threat to marine biota. Nanoplastics, a secondary pollutant in the marine environment, could influence adverse effects of nano-TiO2. The main goal of the present study was to investigate the influence of the differently functionalized polystyrene nanoplastics (COOH-PSNPs, NH2-PSNPs, and Plain-PSNPs) on the acute toxic effects of P25 nano-TiO2 in marine algae Chlorella sp. Three different concentrations of nano-TiO2, 0.25, 0.5, and 1 mg/L, mixed with 5 mg/L of the PSNPs were employed in this study. A substantial increase was noted in mean hydrodynamic sizes of nano-TiO2 when they were mixed with the PSNPs. This hetero-aggregation would reduce the bioavailability of the particles to the algae. The presence of the PSNPs in the mixture reduced the toxicity of nano-TiO2 significantly. A signficant decline in the oxidative stress parameters like total ROS, superoxide (), and hydroxyl radical generation was noted for the mixture of nano-TiO2 with the PSNPs in comparison with the pristine counterparts. The lipid peroxidation, and the antioxidant enzyme activities in the cells correlated well with the reactive species generation results. The treatments with the mixture resulted in notable enhancement in the esterase activity in the cells. The Independent Action model suggested antagonistic interactions between PSNPs and nano-TiO2. The results from this study clearly demonstrate that nano-TiO2 in presence of the PSNPs exerted significantly reduced cytotoxic effects in Chlorella sp, in comparison with the pristine particles.

Multispectroscopy analysis of polystyrene nanoplastic interaction with diastase α-amylase.

The digestive enzyme of plant are generally α-amylase. They functions enzyme that breakdown starch into maltose and sugars. This happens in the endosperm of the seed. Due to pollutants, this process get happened one of emergent xenobiotics are micro and nano plastics. This study involves the interaction 100 nm size of polystyrene nano plastic (PSNPs) on α-amylase. The hyperchromism of α-amylase - PSNPs conjugate's revealed that ground-state complex in a microenvironment. Fluorescence quenching happened when the concentration of PSNPs was increased. The Stern Volmer plot revealed binding constant (Ka) was 1.904 × 1019 M-1. S-1 while the quenching constant (Kq) was 1.036 × 1011 M-1, the blue shift of the peak showed static quenching. The binding constant was KA = 4.2 × 1012, the number of binding site on PSNPs for α-amylase was n = 1.12. The synchronous result showed a gradual reduction in the intensity of Trp residues because when the α-amylase interacts with PSNPs short-range π-π interaction happens around the Trp163 residues. The enzyme activity of α-amylase by 44 % and its IC50 value was found to be 100 µg/mL. The enzyme kinetics (Vmax) analysis showed the type of inhibition with and without PSNPs Vmax 769 and Vmax 303 µg/mL/min, uncompetitive inhibition respectively. The effect of PSNPs on the enzymatic activity of α-amylase showed structural alterations of the protein. Therefore the in vitro and in silico studies were shown evidence of interaction between α-amylase and PSNPs leads to conformational structural changes in α-amylase.

Exposure to polystyrene nanoplastics impairs lipid metabolism in human and murine macrophages in vitro.

The use of polystyrene micro and nanoplastics in cosmetics and personal care products continues to grow every day. The harmful effects of their biological accumulation in organisms of all trophic levels including humans have been reported by several studies. While we have accumulating evidence on the impact of nanoplastics on different organ systems in humans, only a handful of reports on the impact of polystyrene nanoplastics upon direct contact with the immune system at the cellular level are avialable. The present study offers significant evidence on the cell-specific harmful impact of sulfate-modified nanoplastics (S-NPs) on human macrophages. Here we report that exposure of human macrophages to S-NPs (100 µg/mL) stimulated the accumulation of lipids droplets (LDs) in the cytoplasm resulting in the differentiation of macrophages into foam cells. The observed effect was specific for human and murine macrophages but not for other cell types, especially human keratinocytes, liver, and lung cell models. Furthermore, we found that S-NPs mediated LDs accumulation in human macrophages was accompanied by acute mitochondrial oxidative stress. The accumulated LDs were further delivered and accumulated into lysosomes leading to impaired lysosomal clearance. In conclusion, our study reveals that exposure to polystyrene nanoplastics stabilized with anionic surfactants can be a potent stimulus for dysregulation of lipid metabolism and macrophage foam cell formation, a characteristic feature observed during atherosclerosis posing a serious threat to human health.

Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22.

(1) Background: The systemic administration of therapeutic agents to the intestine including cytokines, such as Interleukin-22 (IL-22), is compromised by damage to the microvasculature 24 hrs after total body irradiation (TBI). At that time, there is significant death of intestinal microvascular endothelial cells and destruction of the lamina propria, which limits drug delivery through the circulation, thus reducing the capacity of therapeutics to stabilize the numbers of Lgr5+ intestinal crypt stem cells and their progeny, and improve survival. By its direct action on intestinal stem cells and their villus regeneration capacity, IL-22 is both an ionizing irradiation protector and mitigator. (2) Methods: To improve delivery of IL-22 to the irradiated intestine, we gavaged Lactobacillus-reuteri as a platform for the second-generation probiotic Lactobacillus-reuteri-Interleukin-22 (LR-IL-22). (3) Results: There was effective radiation mitigation by gavage of LR-IL-22 at 24 h after intestinal irradiation. Multiple biomarkers of radiation damage to the intestine, immune system and bone marrow were improved by LR-IL-22 compared to the gavage of control LR or intraperitoneal injection of IL-22 protein. (4) Conclusions: Oral administration of LR-IL-22 is an effective protector and mitigator of intestinal irradiation damage.

Studies on the removal of acid violet 7 dye from aqueous solutions by green ZnO@Fe3O4 chitosan-alginate nanocomposite synthesized using Camellia sinensis extract.

In the present study, ZnO-Fe3O4 nanoparticles were synthesized using the leaves of Camellia sinensis and immobilized in crosslinked alginate-chitosan polymer beads and tested for their photocatalytic applications. The prepared nanocomposite was used for the simultaneous adsorption and photocatalytic degradation of acid violet 7 (AV7) dye. The optimization of reaction conditions ensured higher dye removal efficacy up to 94.21 ± 1.02% using the nanocomposite under UV-C irradiation of 365 nm. The kinetics of the adsorption study fitted well with the pseudo-first-order reaction. The Langmuir model fitted better to the adsorption isotherms compared to the Freundlich and Temkin models. The mechanism of degradation was studied by analyzing the treated AV7 solution. The removal efficiency in tap water, groundwater, and lake water was 83.23 ± 0.4%, 69.13 ± 1.6%, and 67.89 ± 0.3%, respectively. The residual toxicity of the degraded AV7 solution was tested on model organisms like freshwater algae, Scenedesmus sp., and plant model, Allium cepa, demonstrating the lower toxicity of the degraded AV7 product. Finally, a cost-benefit analysis of the experiments was also carried out.

Nanoemulsions: The rising star of antiviral therapeutics and nanodelivery system-current status and prospects.

Nanoemulsions (NEs) of essential oil (EO) have significant potential to target microorganisms, especially viruses. They act as a vehicle for delivering antiviral drugs and vaccines. Narrowing of drug discovery pipeline and the emergence of new viral diseases, especially, coronavirus disease, have created a niche to use NEs for augmenting currently available therapeutic options. Published literature demonstrated that EOs have an inherent broad spectrum of activity across bacterial, fungal, and viral pathogens. The emulsification process significantly improved the efficacy of the active ingredients in the EOs. This article highlights the research findings and patent developments in the last 2 years especially, in EO antiviral activity, antiviral drug delivery, vaccine delivery, viral resistance development, and repurposing EO compounds against SARS-CoV-2.

Impact of acute lymphoblastic leukemia induction therapy: findings from metabolomics on non-fasted plasma samples from a biorepository.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is among the most common cancers in children. With improvements in combination chemotherapy regimens, the overall survival has increased to over 90%. However, the current challenge is to mitigate adverse events resulting from the complex therapy. Several chemotherapies intercept cancer metabolism, but little is known about their collective role in altering host metabolism. OBJECTIVES: We profiled the metabolomic changes in plasma of ALL patients initial- and post- induction therapy. METHODS: We exploited a biorepository of non-fasted plasma samples derived from the Dana Farber Cancer Institute ALL Consortium; these samples were obtained from 50 ALL patients initial- and post-induction therapy. Plasma metabolites and complex lipids were analyzed by high resolution tandem mass spectrometry and differential mobility tandem mass spectrometry. Data were analyzed using a covariate-adjusted regression model with multiplicity adjustment. Pathway enrichment analysis and co-expression network analysis were performed to identify unique clusters of molecules. RESULTS: More than 1200 metabolites and complex lipids were identified in the total of global metabolomics and lipidomics platforms. Over 20% of those molecules were significantly altered. In the pathway enrichment analysis, lipids, particularly phosphatidylethanolamines (PEs), were identified. Network analysis indicated that the bioactive fatty acids, docosahexaenoic acid (DHA)-containing (22:6) triacylglycerols (TAGs), were decreased in the post-induction therapy. CONCLUSION: Metabolomic profiling in ALL patients revealed a large number of alterations following induction chemotherapy. In particular, lipid metabolism was substantially altered. The changes in metabolites and complex lipids following induction therapy could provide insight into the adverse events experienced by ALL patients.

Eco-corona formation on the nanomaterials in the aquatic systems lessens their toxic impact: A comprehensive review.

Recent studies have shown that nanosized materials including plastics as a major cause of concern in the aquatic ecosystem. Fortunately, in the aquatic environment, the surface of the materials is often colonized by exudates of aquatic microorganisms (biofilm), where these materials are attached and surrounded by a secreted matrix with a sticky layer. The significance of these biofilms on the existence and beneficial implications of these pollutants has been studied in recent decades. Here we develop the concept of these pollutants as a complex matrix of polymers to which Extracellular Polymeric Substances (EPS) binds to form eco-corona modifying its density and surface charge of these particles. This review critically integrates the outstanding properties and functions of algal EPS in the aquatic environment and their dynamic interactions of early colonization on the surface of these pollutants, the impact of biofilm formation on stability, reactivity and, toxicity from the current literature. Due to the modifications of the environmental processes, EPS can have an impact on the toxicity thus special attention is focused on their behavior to decrease the toxicity of the pollutants in the aquatic environment. Although there has been an increasing number of researches in this area, further progress is needed to explore the extent to which ecological processes could be impacted, including the modifications in the behavior of aquatic pollutants. Thus, this review provides a recent perspective into the mechanisms of how eco-corona formation mitigates the toxicity of nanomaterials prevalent in aquatic ecosystems.

Prospects on the nano-plastic particles internalization and induction of cellular response in human keratinocytes.

BACKGROUND: Today, cosmetic products are very popular with both men and women to improve their appearance and increase their social acceptability. RESULTS: In this study, nano-sized (30-300 nm) plastic particles were isolated from the commercial face-scrubs and treated on the human keratinocytes. The observed adherence of polyethylene nano-plastics (PENPs), polystyrene NPs (PSNPs), and face-scrubs isolated nano-plastics (NPs) on the keratin layer reveals a significant attachment of NPs from the cosmetics that are applied on the skin for a short duration. This attachment property could facilitate further adherence of protein molecules on NPs and the protein-corona formation. The protein-corona mimics protein aggregates, thereby triggers macropinocytosis, followed by the macropinolysosomal process in the cell. These internalized NPs induced the concentration-dependent cytotoxic, cytostatic and cytoprotective activity in keratinocytes. Both single dose and chronic long-term exposure of lethal and sub-lethal concentrations of NPs resulted in oxidative stress-mediated down-regulation of cell growth and proliferation inhibition. Autophagic structures and premature aging were also observed using an electron microscopy and a senescence marker, respectively in the NPs internalized HaCaT cells incubated in a fresh, NPs-free medium. CONCLUSION: Though 2D culture models have many limitations, it produces significant conceptual advancements. This work provides an insight into the NPs concentration-dependent regulatory, cytoprotective, and cytotoxic effects in HaCaT cells. However, 3D model studies are required to identify the detailed mechanisms of NPs toxicity and cytoprotective events in cells at the molecular level.

Development of biogenic bimetallic Pd/Fe nanoparticle-impregnated aerobic microbial granules with potential for dye removal.

The objective of this study was to develop bimetallic core-shell Pd/Fe nanoparticles on the surface of aerobic microbial granules (Bio-Pd/Fe) and to evaluate their dye removal potential using a representative dye, methyl orange (MO). The aerobic microbial granules (1.5 ± 0.32 mm) were grown for 70 days in a 3-L glass sequencing batch reactor (SBR) with a 12-h cycle time. The Bio-Pd/Fe formation was catalyzed by the Bio-H2 gas produced by the granules. The developed Bio-Pd/Fe was further used for MO removal from aqueous solutions, and the reaction parameters were optimized by response surface methodology (RSM). The XRD, SEM, EDAX, elemental mapping, and XPS studies confirmed the formation of Bio-Pd/Fe. Under the optimized removal conditions, 99.33% MO could be removed by Bio-Pd/Fe, whereas removal by Bio-Pd, Bio-Fe, aerobic microbial granules, and heat-killed granules were found to be quite low (68.91 ± 0.2%, 76.8 ± 0.3%, 19.8 ± 0.6%, and 6.59 ± 0.2%, respectively). The mechanism of removal was investigated by UV-visible spectroscopy, redox potential analysis, HR-LCMS analyses of the solution phase, and XRD and XPS analyses of the solid sorbent. The degradation products of MO exhibited m/z values corresponding to 292, 212, and 160 m/z. The remnant toxicity of the intermediate degradation products was analysed using freshwater algae, Scenedesmus sp. And Allium cepa, as indicator organisms. These assays suggested that after the treatment with Bio-Pd/Fe, MO was transformed to a lesser toxic form.

Mechanism of the oxidative stress-mediated increase in lipid accumulation by the bacterium, R. opacus PD630: Experimental analysis and genome-scale metabolic modeling.

Appropriate species of oleaginous bacteria, with their high growth rates and lipid accumulation capabilities, can be good contenders for industrial triacylglycerol (TAG) production, compared to microalgae. Further, oxidative stress (OS) can be used to significantly increase TAG yields in oleaginous microbes, but the mechanism is unexplored. In a first, this study explored the mechanism behind OS-mediated increase in TAG accumulation by the bacterium, Rhodococccus opacus PD630, through experimental analysis and metabolic modelling. Two mechanisms that could increase acetyl-CoA (TAG-precursor) levels were hypothesized based on literature information. One was OS-mediated inactivation of the aconitase (TCA cycle), and another was the inactivation of the triosephosphate isomerase (TPI; glycolysis). The results negated the involvement of aconitase in increased acetyl-CoA levels. Analysis of the metabolic model showed that inactivation of TPI, re-routed the flux through the pentose phosphate pathway (PPP), supplying both NADPH and acetyl-CoA for TAG synthesis. Additionally, inactivation of TPI increased TAG flux by 143%, whereas, inactivating both TPI and aconitase, increased it by 152%. We present experimental evidence for OS-mediated decrease in TPI activity and increase in activity of glucose-6-phosphate dehydrogenase (PPP enzyme). The findings indicate that increased flux through PPP can be explored to improve TAG accumulation on a large-scale.

Eco-corona formation lessens the toxic effects of polystyrene nanoplastics towards marine microalgae Chlorella sp.

Unabated use of nanoplastics (<1 µm) in the consumer products and their consequent release to the marine environment poses a substantial threat to the marine ecosystem. The toxic impact of the nanoplastics on marine microalgae is yet to be explored in detail, and the role of reactive oxygen species generation remains largely unclear. The algal exudates constitute a significant part of the natural organics present in the marine system that may readily adsorb over the nanoplastics to form eco-corona. In the current work a marine alga, Chlorella sp., was considered a bioindicator organism and the effects of eco-corona formation in lessening the toxic impact of the nanoplastics was analyzed. Three differently functionalized polystyrene nanoplastics (PS NPs): Aminated (NH2-PS NPs), Carboxylated (COOH-PS NPs) and Plain nanoplastics were aged (12, 24, and 48 h) in the EPS containing medium to facilitate eco-corona formation. Decline in cell viability, membrane integrity, and photosynthetic yield were considered to be principle toxicity indicators. The role of oxidative stress as key mode of action (MOA) was studied considering generation of overall reactive oxygen species, and specific radicals (hydroxyl and superoxide) as relevant markers. The changes in antioxidant enzyme activities (superoxide dismutase, and catalase) were also measured. The results clearly indicate a significant decline in the oxidative stress and corresponding lessening of the toxic effects due to eco-corona formation on the PS NPs. The response varied with surface charge on the NPs and ageing duration. Considering the increasing importance of the nanoplastics as one of the major emerging pollutants in marine ecosystem, this study strongly suggests that the EPS mediated eco-corona formation may substantially lessen their toxic burden.

Differential growth and metabolic responses induced by nano-scale zero valent iron in germinating seeds and seedlings of Oryza sativa L. cv. Swarna.

Since development of antioxidant defence system is high energy demanding event, innate defence system and stress tolerance of plant is strictly governed by plant age. This study is aimed towards evaluating variation of tolerance in germinating seeds and seedlings of Oryza sativa L. cv. Swarna against nano-scale zero valent iron (nZVI). A comparative study of several physiological and biochemical parameters have been carried out among 2 distinct plant groups, Group I treated with variable concentrations of nZVI (50, 100, 150 and 200 mg L-1) during germination and Group II treated with similar nZVI doses on 7th day after germination. Upon treatment with higher nZVI concentrations, Group I seedlings showed susceptibility towards oxidative stress while Group II seedlings showed tolerance against these higher doses of nZVI. Significant growth enhancement was observed upon treatment with 50-150 mg L-1 nZVI, since up-regulation of plant's endogenous antioxidant system protected relatively aged Group II seedlings from oxidative damages. Hierarchical clustering based on overall physiological, biochemical and stress parameters confirmed that in Group I seedlings 100-200 mg L-1 nZVI treatments were toxic where as in Group II seedlings 50-150 mg L-1 nZVI treatments showed growth promoting effects. This differential response is due to developmental stage related resistance in plants.

Distribution-free simultaneous tests for location-scale and Lehmann alternative in two-sample problem.

The paper deals with the classical two-sample testing problem for the equality of two populations, one of the most fundamental problems in biomedical experiments and case-control studies. The most familiar alternatives are the difference in location parameters or the difference in scale parameters or in both the parameters of the population density. All the tests designed for classical location or scale or location-scale alternatives assume that there is no change in the shape of the distribution. Some authors also consider the Lehmann-type alternative that addresses the change in shape. Two-sample tests under Lehmann alternative assume that the location and scale parameters are invariant. In real life, when a shift in the distribution occurs, one or more of the location, scale, and shape parameters may change simultaneously. We refer to change of one or more of the three parameters as a versatile alternative. Noting the dearth of literature for the equality two populations against such versatile alternative, we introduce two distribution-free tests based on the Euclidean and Mahalanobis distance. We obtain the asymptotic distributions of the two test statistics and study asymptotic power. We also discuss approximating p-values of the proposed tests in real applications with small samples. We compare the power performance of the two tests with several popular existing distribution-free tests against various fixed alternatives using Monte Carlo. We provide two illustrations based on biomedical experiments. Unlike existing tests which are suitable only in certain situations, proposed tests offer very good power in almost all types of shifts.

Tetracycline removal using green synthesized bimetallic nZVI-Cu and bentonite supported green nZVI-Cu nanocomposite: A comparative study.

Antibiotics, one of the most abundant contaminants in the natural water systems possess various difficulties to remediate through conventional water treatment methods. Tetracycline (TC) remains one of the most widely used antibiotics for human and veterinary applications because of its broad-spectrum antibacterial activity. In the current study, we have employed nano zero-valent technology-based antibiotic remediation. In a first of its kind work, we applied bimetallic nZVI-Cu nanoparticles synthesized using pomegranate rind extract for remediation. TC removal of 72 ±â€¯0.5% (initial TC concentration 10 mg/L) was obtained with the nZVI-Cu concentration of 750 mg/L at pH 7. To overcome the colloidal instability and enhance TC removal further, the bimetallic nanoparticles were formed in-situ over bentonite. The bentonite supported composite (B/nZVI-Cu) was used to treat TC an initial concentration of 10 mg/L and the results confirmed significant enhancement in removal with a substantially decreased nanoparticle loading. Using only 150 mg/L of B/nZVI-Cu at pH 7, 95 ±â€¯0.05% of TC could be removed. The nanoparticles and the composites were characterized by SEM, FT-IR, and XRD analyses. The removal process was followed by UV-Visible analyses in conjunction with TOC, ORP and LCMS measurements. For treatment using B/nZVI-Cu, the reusability of the composite was established up to three cycles of operation, and the process was validated in the real water systems. Substantially decreased residual toxicity of the composite treated TC solution lends credence to the environmental sustainability of the process.

Transient High Pressure in Pancreatic Ducts Promotes Inflammation and Alters Tight Junctions via Calcineurin Signaling in Mice.

BACKGROUND & AIMS: Pancreatitis after endoscopic retrograde cholangiopancreatography (PEP) is thought to be provoked by pancreatic ductal hypertension, via unknown mechanisms. We investigated the effects of hydrostatic pressures on the development of pancreatitis in mice. METHODS: We performed studies with Swiss Webster mice, B6129 mice (controls), and B6129 mice with disruption of the protein phosphatase 3, catalytic subunit, ßisoform gene (Cnab-/- mice). Acute pancreatitis was induced in mice by retrograde biliopancreatic ductal or intraductal infusion of saline with a constant hydrostatic pressure while the proximal common bile duct was clamped -these mice were used as a model of PEP. Some mice were given pancreatic infusions of adeno-associated virus 6-nuclear factor of activated T-cells-luciferase to monitor calcineurin activity or the calcineurin inhibitor FK506. Blood samples and pancreas were collected at 6 and 24 hours and analyzed by enzyme-linked immunosorbent assay, histology, immunohistochemistry, or fluorescence microscopy. Ca2+ signaling and mitochondrial permeability were measured in pancreatic acinar cells isolated 15 minutes after PEP induction. Ca2+-activated phosphatase calcineurin within the pancreas was tracked in vivo over 24 hours. RESULTS: Intraductal pressures of up to 130 mm Hg were observed in the previously reported model of PEP; we found that application of hydrostatic pressures of 100 and 150 mm Hg for 10 minutes consistently induced pancreatitis. Pancreatic tissues had markers of inflammation (increased levels of interleukin [IL] 6, IL1B, and tumor necrosis factor), activation of signal transducer and activator of transcription 3, increased serum amylase and IL6, and loss of tight junction integrity. Transiently high pressures dysregulated Ca2+ processing (reduced Ca2+ oscillations and an increased peak plateau Ca2+ signal) and reduced the mitochondrial membrane potential. We observed activation of pancreatic calcineurin in the pancreas in mice. Cnab-/- mice, which lack the catalytic subunit of calcineurin, and mice given FK506 did not develop pressure-induced pancreatic inflammation, edema, or loss of tight junction integrity. CONCLUSIONS: Transient high ductal pressure produces pancreatic inflammation and loss of tight junction integrity in a mouse model of PEP. These processes require calcineurin signaling. Calcineurin inhibitors might be used to prevent acute pancreatitis that results from obstruction.

Insights into the interaction of key biofilm proteins in Pseudomonas aeruginosa PAO1 with TiO2 nanoparticle: An in silico analysis.

Pseudomonas aeruginosa is a pathogenic biofilm forming bacteria which exist in wide range of environments such as water, soil and human body. In an earlier study, we used a system biology approach based analysis of biofilm forming genes of P. aeruginosa and their possible role in TiO2 nanoparticle binding. The major protein of P. aeruginosa targeted by TiO2 was found to be KatA, a major catalase required for H2O2 resistance and acute virulence and the direct interacting protein partners of KatA were found to be DnaK, Hfq, RpoA and RpoS. To understand the protein-protein physical interaction characteristic of these key proteins involved in biofilm related processes, homology modeling, docking and molecular dynamic simulation were performed. For all these proteins, physical and chemical properties, amino acid composition, nest and cleft analysis were performed using online tools. The interactions between TiO2NPs-KatA and four protein-protein complexes such as KatA-DnaK, KatA-Hfq, KatA-RpoA and KatA-RpoS were studied. Our results indicate that all four key proteins and TiO2NPs can have stable complexation with KatA. The study has given enough clues to understand the interaction of TiO2NPs with P. aeruginosa biofilm in natural environment. Further investigations could lead to development of TiO2NPs based therapeutic and sanitary interventions to combat this pathogenic bacterium.