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1.
RSC Adv ; 14(2): 1072-1081, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38174238

ABSTRACT

Utilization of efficient, stable and reusable catalysts for wastewater treatment and catalytic elimination of toxic pollutants is a challenge among researchers. This present work shows the synthesis of high-surface-activity Ag nanoparticle decorated gC3N4 modified MCM-41 and its efficiency towards catalytic hydrogenation of organic dye in the presence of reducing agent NaBH4. The proposed mechanism is based on the transfer of H+ and 2e- between the dye and the catalyst. Adsorption of dye stuff on the catalyst is a rate-determining step and is accelerated by the MCM-41 support which enhances the surface area. The catalytic efficiency and optimum time requirement were examined through the adsorption-desorption equilibrium, pseudo-first-order reaction kinetic model for the dye. The result obtained was 98% catalytic efficiency followed by the catalytic hydrogenation reaction.

2.
Environ Sci Pollut Res Int ; 31(4): 5540-5554, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38127232

ABSTRACT

The performance of advanced materials in environmental applications using green energy is the tremendous interest among researchers. The visible light responsive BiFeO3 (BFO), BiFeO3/CuS (BFOC), and Ag-loaded BiFeO3/CuS (Ag-BFOC) heterostructures have been synthesized by reflux method followed by hydrothermal and wetness impregnation method. These synthesized composites are well characterized through X-ray diffraction, UV diffuse reflectance spectroscopy, scanning electron microscope, and Fourier transfer infrared spectroscopy techniques. Compared with BFO and BFOC, Ag-BFOC exhibits the highest photocatalytic performance towards the degradation of antibiotics ciprofloxacin (76%) within 120-min time and also showed better antibacterial performance towards gram-negative (Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii) bacteria. Moreover, the novelty of the present work is the addition of CuS on the surface of BiFeO3 from heterojunction type II and facilitates the electron-hole channelization at the interfaces between BiFeO3 and CuS. Again, the loading of Ag on BiFeO3/CuS helps in shifting the absorption band towards the red end, is eligible to absorb more sunlight due to surface plasmon resonance effect, improves the separation efficiency of photo-generated charge carriers, and enhances the photocatalytic degradation of ciprofloxacin. The antibacterial property of Ag gives a best result towards antimicrobial activity. The prepared composites have proved their durability and stability by four successive cycles and prove the versatility of the composite.


Subject(s)
Anti-Bacterial Agents , Silver , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Silver/chemistry , Photolysis , Light , Ciprofloxacin/pharmacology
3.
J Fungi (Basel) ; 8(11)2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36422036

ABSTRACT

The Kv1.3 channel has become a therapeutic target for the treatment of various diseases. Several Kv1.3 channel blockers have been characterized from scorpion venom; however, extensive studies require amounts of toxin that cannot be readily obtained directly from venoms. The Pichia pastoris expression system provides a cost-effective approach to overcoming the limitations of chemical synthesis and E. coli recombinant expression. In this work, we developed an efficient system for the production of three potent Kv1.3 channel blockers from different scorpion venoms: Vm24, AnTx, and Ts6. Using the Pichia system, these toxins could be obtained in sufficient quantities (Vm24 1.6 mg/L, AnTx 46 mg/L, and Ts6 7.5 mg/L) to characterize their biological activity. A comparison was made between the activity of tagged and untagged recombinant peptides. Tagged Vm24 and untagged AnTx are nearly equivalent to native toxins in blocking Kv1.3 (Kd = 4.4 pM and Kd = 0.72 nM, respectively), whereas untagged Ts6 exhibits a 53-fold increase in Kd (Kd = 29.1 nM) as compared to the native peptide. The approach described here provides a method that can be optimized for toxin production to develop more selective and effective Kv1.3 blockers with therapeutic potential.

4.
Pathog Dis ; 80(1)2022 07 21.
Article in English | MEDLINE | ID: mdl-35704614

ABSTRACT

This study has investigated a total of 51 Acinetobacter baumannii isolates for the prevalence of resistant determinants in tigecycline susceptible and non-susceptible clinical isolates of A. baumannii. Antimicrobial susceptibility testing revealed 74% of isolates were tigecycline resistant. Mutations in RND-efflux pump regulatory genes and the expression of efflux pump genes were measured in tigecycline resistant isolates. There was a strong co-relation between the blaNDM-1 and armA wherein majority of the isolates that are positive for blaNDM-1 have also harbored armA. Compared with TSAB (tigecycline susceptible A. baumannii), TNAB (tigecycline non-susceptible A. baumannii) isolates show increased distribution of blaNDM-1 (P = 0.048), blaIMP-1 (P< 0.0001) and blaOXA-51 (P = 0.0029) carbapenemase genes. The variants of RND-efflux pump regulatory genes due to amino-acid mutations in adeS (F12S, K84E, W61R, N268H and Q299R) and adeL (G21R and Q262R) were identified in tigecycline resistant isolates as well as ISAba1 mediated disruption of adeN were observed causing overexpression of adeIJK efflux pump. Additionally, mutations in adeRS were also associated with increased expression of adeABC efflux pump. Besides, TNAB isolates showed significantly (P< 0.0001) higher ability of biofilm formation as compared to TSAB isolates. The tigecycline resistance due to mutations in contemporary A. baumannii isolates having a higher ability to form biofilm may pose therapeutic difficulties.


Subject(s)
Acinetobacter baumannii , Acinetobacter baumannii/genetics , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Drug Resistance, Multiple, Bacterial/genetics , Membrane Transport Proteins , Microbial Sensitivity Tests , Mutation , Tigecycline/metabolism , Tigecycline/pharmacology
5.
Respir Res ; 22(1): 99, 2021 Apr 06.
Article in English | MEDLINE | ID: mdl-33823870

ABSTRACT

BACKGROUND: COVID-19 pneumonia has been associated with severe acute hypoxia, sepsis-like states, thrombosis and chronic sequelae including persisting hypoxia and fibrosis. The molecular hypoxia response pathway has been associated with such pathologies and our recent observations on anti-hypoxic and anti-inflammatory effects of whole aqueous extract of Adhatoda Vasica (AV) prompted us to explore its effects on relevant preclinical mouse models. METHODS: In this study, we tested the effect of whole aqueous extract of AV, in murine models of bleomycin induced pulmonary fibrosis, Cecum Ligation and Puncture (CLP) induced sepsis, and siRNA induced hypoxia-thrombosis phenotype. The effect on lung of AV treated naïve mice was also studied at transcriptome level. We also determined if the extract may have any effect on SARS-CoV2 replication. RESULTS: Oral administration AV extract attenuates increased airway inflammation, levels of transforming growth factor-ß1 (TGF-ß1), IL-6, HIF-1α and improves the overall survival rates of mice in the models of pulmonary fibrosis and sepsis and rescues the siRNA induced inflammation and associated blood coagulation phenotypes in mice. We observed downregulation of hypoxia, inflammation, TGF-ß1, and angiogenesis genes and upregulation of adaptive immunity-related genes in the lung transcriptome. AV treatment also reduced the viral load in Vero cells infected with SARS-CoV2. CONCLUSION: Our results provide a scientific rationale for this ayurvedic herbal medicine in ameliorating the hypoxia-hyperinflammation features and highlights the repurposing potential of AV in COVID-19-like conditions.


Subject(s)
Anti-Inflammatory Agents/pharmacology , COVID-19 Drug Treatment , Drug Repositioning , Hypoxia/drug therapy , Justicia , Lung/drug effects , Plant Extracts/pharmacology , Pneumonia/prevention & control , Pulmonary Fibrosis/drug therapy , Sepsis/drug therapy , Animals , Anti-Inflammatory Agents/isolation & purification , Bleomycin , COVID-19/metabolism , COVID-19/virology , Cecum/microbiology , Cecum/surgery , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Hypoxia/genetics , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor-Proline Dioxygenases/genetics , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Inflammation Mediators/metabolism , Justicia/chemistry , Ligation , Lung/metabolism , Lung/microbiology , Lung/pathology , Male , Mice, Inbred BALB C , Mice, Inbred C57BL , Plant Extracts/isolation & purification , Pneumonia/genetics , Pneumonia/metabolism , Pneumonia/microbiology , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/genetics , Pulmonary Fibrosis/metabolism , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Sepsis/genetics , Sepsis/metabolism , Sepsis/microbiology , Transcriptome
6.
Am J Physiol Lung Cell Mol Physiol ; 320(5): L757-L769, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33565386

ABSTRACT

Severe asthma is a chronic airway disease that exhibits poor response to conventional asthma therapies. Growing evidence suggests that elevated hypoxia increases the severity of asthmatic inflammation among patients and in model systems. In this study, we elucidate the therapeutic effects and mechanistic basis of Adhatoda vasica (AV) aqueous extract on mouse models of acute allergic as well as severe asthma subtypes at physiological, histopathological, and molecular levels. Oral administration of AV extract attenuates the increased airway resistance and inflammation in acute allergic asthmatic mice and alleviates the molecular signatures of steroid (dexamethasone) resistance like IL-17A, KC (murine IL-8 homologue), and HIF-1α (hypoxia-inducible factor-1α) in severe asthmatic mice. AV inhibits HIF-1α levels through restoration of expression of its negative regulator-PHD2 (prolyl hydroxylase domain-2). Alleviation of hypoxic response mediated by AV is further confirmed in the acute and severe asthma model. AV reverses cellular hypoxia-induced mitochondrial dysfunction in human bronchial epithelial cells-evident from bioenergetic profiles and morphological analysis of mitochondria. In silico docking of AV constituents reveal higher negative binding affinity for C and O-glycosides for HIF-1α, IL-6, Janus kinase 1/3, TNF-α, and TGF-ß-key players of hypoxia inflammation. This study for the first time provides a molecular basis of action and effect of AV whole extract that is widely used in Ayurveda practice for diverse respiratory ailments. Further, through its effect on hypoxia-induced mitochondrial dysfunction, the study highlights its potential to treat severe steroid-resistant asthma.


Subject(s)
Asthma/drug therapy , Hypoxia/complications , Justicia/chemistry , Mitochondria/drug effects , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Pneumonia/prevention & control , Animals , Asthma/etiology , Asthma/metabolism , Asthma/pathology , Disease Models, Animal , Gene Expression Regulation , Male , Mice , Mice, Inbred BALB C , Mitochondria/metabolism , Mitochondria/pathology , Pneumonia/etiology , Pneumonia/metabolism , Pneumonia/pathology
7.
Am J Respir Cell Mol Biol ; 60(4): 399-412, 2019 04.
Article in English | MEDLINE | ID: mdl-30335467

ABSTRACT

The asthma candidate gene inositol polyphosphate 4-phosphatase type I A (INPP4A) is a lipid phosphatase that negatively regulates the PI3K/Akt pathway. Destabilizing genetic variants of INPP4A increase the risk of asthma, and lung-specific INPP4A knockdown induces asthma-like features. INPP4A is known to localize intracellularly, and its extracellular presence has not been reported yet. Here we show for the first time that INPP4A is secreted by airway epithelial cells and that extracellular INPP4A critically inhibits airway inflammation and remodeling. INPP4A was present in blood and BAL fluid, and this extracellular INPP4A was reduced in patients with asthma and mice with allergic airway inflammation. In both naive mice and mice with allergic airway inflammation, antibody-mediated neutralization of extracellular INPP4A potentiated PI3K/Akt signaling and induced airway hyperresponsiveness, with prominent airway remodeling, subepithelial fibroblast proliferation, and collagen deposition. The link between extracellular INPP4A and fibroblasts was investigated in vitro. Cultured airway epithelial cells secreted enzymatically active INPP4A in extracellular vesicles and in a free form. Extracellular vesicle-mediated transfer of labeled INPP4A, from epithelial cells to fibroblasts, was observed. Inhibition of such transfer by anti-INPP4A antibody increased fibroblast proliferation. We propose that secretory INPP4A is a novel "paracrine" layer of the intricate regulation of lung homeostasis, by which airway epithelium dampens PI3K/Akt signaling in inflammatory cells or local fibroblasts, thereby limiting inflammation and remodeling.


Subject(s)
Airway Remodeling/physiology , Asthma/pathology , Phosphatidylinositol 3-Kinases/metabolism , Phosphoric Monoester Hydrolases/metabolism , Respiratory Hypersensitivity/pathology , Airway Remodeling/genetics , Animals , Asthma/blood , Asthma/genetics , Cell Line, Transformed , Cell Line, Tumor , Cell Proliferation , Disease Models, Animal , Fibroblasts/metabolism , Humans , Lung/pathology , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Phosphoric Monoester Hydrolases/blood , Phosphoric Monoester Hydrolases/genetics , Respiratory Hypersensitivity/genetics , Signal Transduction/genetics
8.
Int Immunopharmacol ; 55: 20-27, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29220719

ABSTRACT

Obesity is a high risk factor for diseases such as cardiovascular, metabolic syndrome and asthma. Obese-asthma is another emerging phenotype in asthma which is typically refractive to steroid treatment due to its non-classical features such as non-eosinophilic cellular inflammation. The overall increased morbidity, mortality and economical burden in asthma is mainly due to steroid resistant asthma. In the present study, we used high fat diet induced obese mice which when sensitized with house dust mite (HDM) showed steroid resistant features. While the steroid, dexamethasone (DEX), treatment to high fat fed naïve mice could not reduce the airway hyperresponsiveness (AHR) induced by high fat, DEX treatment to high fat fed allergic mice could not reduce the HDM allergen induced airway remodeling features though it reduced airway inflammation. Further, these HDM induced high fat fed mice with or without DEX treatment had shown the increased activity and expression of arginase as well as the inducible nitric oxide synthase (iNOS) expression. However, DEX treatment had reduced the expressions of high iNOS and arginase I in control chow diet fed mice. Thus, we speculate that the steroid resistance seen in human obese asthmatics could be stemming from altered NO metabolism and its induced airway remodeling and with further investigations, it would encourage new treatments specific to obese-asthma phenotype.


Subject(s)
Airway Remodeling/drug effects , Asthma/drug therapy , Dexamethasone/therapeutic use , Obesity/drug therapy , Respiratory Hypersensitivity/drug therapy , Animals , Antigens, Dermatophagoides/immunology , Arginase/genetics , Arginase/metabolism , Diet, High-Fat , Drug Resistance , Humans , Male , Mice , Mice, Inbred C57BL , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Pyroglyphidae/immunology
9.
Nat Commun ; 8(1): 815, 2017 10 09.
Article in English | MEDLINE | ID: mdl-28993609

ABSTRACT

Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3+ regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that the forkhead family transcription factor Foxo1 is required for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1. Mechanistically, Foxo1 binds and transactivates IL-9 and IRF4 promoters in Th9, Th17 and iTreg cells. Furthermore, loss of Foxo1 attenuates IL-9 in mouse and human Th9 and Th17 cells, and ameliorates allergic inflammation in asthma. Our findings thus identify that Foxo1 is essential for IL-9 induction in Th9 and Th17 cells.The transcription factor Foxo1 can control regulatory T cell and Th1 function. Here the authors show that Foxo1 is also critical for IL-9 production by Th9 cells and other IL-9-producing cells.

10.
Sci Rep ; 7(1): 9565, 2017 08 29.
Article in English | MEDLINE | ID: mdl-28851976

ABSTRACT

Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15-lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI). HODE treatment to allergic mice further increased airway hyperresponsiveness and goblet metaplasia. Treatment with dexamethasone was associated with increased neutrophilic inflammation in HODE treated allergic mice; unlike control allergic mice that showed resolution of inflammation. HODE induced loss of steroid sensitivity was associated with increased p-NFkB in mice and reduced GR-α transcript levels in cultured human bronchial epithelia. In summary, HODE modifies typical AAI to recapitulate many of the phenotypic features seen in severe steroid unresponsive asthma. We speculate that since HODE is a natural metabolite, it may be relevant to the increased asthma severity and steroid insensitivity in patients who are obese or consume high fat diets. Further characterization of HODE induced steroid insensitivity may clarify the mechanisms.


Subject(s)
Anti-Asthmatic Agents/pharmacology , Asthma/metabolism , Drug Resistance , Linoleic Acid/metabolism , NF-kappa B/metabolism , Steroids/pharmacology , Animals , Asthma/drug therapy , Asthma/pathology , Disease Models, Animal , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Humans , Hypersensitivity/drug therapy , Hypersensitivity/immunology , Hypersensitivity/metabolism , Hypersensitivity/pathology , Lipid Metabolism , Mice , Receptors, Glucocorticoid/metabolism , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology
11.
Int Immunopharmacol ; 26(1): 246-56, 2015 May.
Article in English | MEDLINE | ID: mdl-25863236

ABSTRACT

This is a follow-up study of our previous work in which we screened a series of Vasicine analogues for their anti-inflammatory activity in a preventive OVA induced murine model of asthma. The study demonstrated that R8, one of the analogues, significantly suppressed the Th2 cytokine production and eosinophil recruitment to the airways. In the present study, we have been using two standard experimental murine models of asthma, where the mice were treated with R8 either during (preventive use) or after (therapeutic use) the development of asthma features. In the preventive model, R8 reduced inflammatory cell infiltration to the airways, OVA specific IgE and Th2 cytokine production. Also, the R8 treatment in the therapeutic model decreased methacholine induced AHR, Th2 cytokine release, serum IgE levels, infiltration of inflammatory cells into the airways, phosphorylation of STAT6 and expression of GATA3. Moreover, R8 not only reduced goblet cell metaplasia in asthmatic mice but also reduced IL-4 induced Muc5AC gene expression in human alveolar basal epithelial cells. Further, R8 attenuated IL-4 induced differentiation of murine splenocytes into Th2 cells in vitro. So, we may deduce that R8 treatment profoundly reduced asthma features by attenuating the differentiation of T cells into Th2 cells by interfering with the binding of IL-4 to its receptor in turn decreasing the phosphorylation of STAT6 and expression of GATA3 in murine model of asthma. These preclinical findings suggest a possible therapeutic role of R8 in allergic asthma.


Subject(s)
Alkaloids/chemistry , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Azepines/therapeutic use , Quinazolines/chemistry , Quinazolinones/therapeutic use , STAT6 Transcription Factor/antagonists & inhibitors , Animals , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/chemistry , Anti-Asthmatic Agents/toxicity , Asthma/immunology , Asthma/metabolism , Azepines/administration & dosage , Azepines/chemistry , Azepines/toxicity , Cytokines/analysis , Cytokines/genetics , Disease Models, Animal , Gene Expression/drug effects , Immunoglobulin E/blood , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Mice, Inbred BALB C , Ovalbumin/immunology , Quinazolinones/administration & dosage , Quinazolinones/chemistry , Quinazolinones/toxicity , Toxicity Tests
12.
Int Immunopharmacol ; 15(3): 597-605, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23453702

ABSTRACT

Even though neurogenic axis is well known in asthma pathogenesis much attention had not been given on this aspect. Recent studies have reported the importance of TRP channels, calcium-permeable ion channels and key molecules in neurogenic axis, in asthma therapeutics. The role of TRPV1 channels has been underestimated in chronic respiratory diseases as TRPV1 knockout mice of C57BL/6 strains did not attenuate the features of these diseases. However, this could be due to strain differences in the distribution of airway capsaicin receptors. Here, we show that TRPV1 inhibition attenuates IL-13 induced asthma features by reducing airway epithelial injury in BALB/c mice. We found that IL-13 increased not only the lung TRPV1 levels but also TRPV1 expression in bronchial epithelia in BALB/c rather than in C57BL/6 mice. TRPV1 knockdown attenuated airway hyperresponsiveness, airway inflammation, goblet cell metaplasia and subepithelial fibrosis induced by IL-13 in BALB/c mice. Further, TRPV1 siRNA treatment reduced not only the cytosolic calpain and mitochondrial calpain 10 activities in the lung but also bronchial epithelial apoptosis indicating that TRPV1 siRNA might have corrected the intracellular and intramitochondrial calcium overload and its consequent apoptosis. Knockdown of IL-13 in allergen induced asthmatic mice reduced TRPV1, cytochrome c, and activities of calpain and caspase 3 in lung cytosol. Thus, these findings suggest that induction of TRPV1 with IL-13 in bronchial epithelia could lead to epithelial injury in in vivo condition. Since TRPV1 expression is correlated with human asthma severity, TRPV1 inhibition could be beneficial in attenuating airway epithelial injury and asthma features.


Subject(s)
Asthma/immunology , Respiratory Mucosa/immunology , TRPV Cation Channels/metabolism , Animals , Asthma/genetics , Bronchial Hyperreactivity/genetics , Cytokines/metabolism , Disease Models, Animal , Gene Expression Regulation/genetics , Gene Knockdown Techniques , Goblet Cells/pathology , Humans , Interleukin-13/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , RNA, Small Interfering/genetics , TRPV Cation Channels/genetics
13.
Tetrahedron Lett ; 51(11): 1462-1466, 2010 Mar 17.
Article in English | MEDLINE | ID: mdl-20379349

ABSTRACT

Novel retinoids 1-3 containing perillyl alcohol were synthesized through the addition of perillyl alcohol to the activated carboxylic acids (retinoids) promoted by DCC (N, N'-Dicylohexyl cabodiimide). A set of structurally and functionally diverse perillyl alcohol derivatives of retinoids were obtained in good yields (78-82%). Biological evaluation of these novel hybrid compounds (containing retinoids and perillyl alcohol) is currently underway in our laboratory.

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