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Tuberculosis (TB) remains a critical health threat, particularly with the emergence of multidrug-resistant strains. This demands attention from scientific communities and healthcare professionals worldwide to develop effective treatments. The enhanced intracellular survival (Eis) protein is an acetyltransferase enzyme of Mycobacterium tuberculosis that functions by adding acetyl groups to aminoglycoside antibiotics, which interferes with their ability to bind to the bacterial ribosome, thereby preventing them from inhibiting protein synthesis and killing the bacterium. Therefore, targeting this protein accelerates the chance of restoring the aminoglycoside drug activity, thereby reducing the emergence of drug-resistant TB. For this, we have screened 406,747 natural compounds from the Coconut database against Eis protein. Based on MM/GBSA rescoring binding energy, the top 5 most prominent natural compounds, viz. CNP0187003 (- 96.14 kcal/mol), CNP0176690 (- 93.79 kcal/mol), CNP0136537 (- 92.31 kcal/mol), CNP0398701 (- 91.96 kcal/mol), and CNP0043390 (- 91.60 kcal/mol) were selected. These compounds exhibited the presence of a substantial number of hydrogen bonds and other significant interactions confirming their strong binding affinity with the Eis protein during the docking process. Subsequently, the MD simulation of these compounds exhibited that the Eis-CNP0043390 complex was the most stable, followed by Eis-CNP0187003 and Eis-CNP0176690 complex, further verified by binding free energy calculation, principal component analysis (PCA), and Free energy landscape analysis. These compounds demonstrated the most favourable results in all parameters utilised for this investigation and may have the potential to inhibit the Eis protein. There these findings will leverage computational techniques to identify and develop a natural compound inhibitor as an alternative for drug-resistant TB.
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In this study, the potential of ultrafiltered xylano-pectinolytic enzymatic bleaching approach was investigated, for manufacturing wheat straw-based paper. The enzymatic step was found to be most effective, with xylanase-pectinase dose of 4-1.7 IU/g pulp and time period of 180 min. The absorption spectra of the pulp free filtrate samples obtained after treatment of the pulp with ultrafiltered enzymes showed the removal of more impurities, in comparison to the treatment with crude enzymes. Microscopic analysis also showed the removal of lignin impurities in enzymatically bleached pulp samples. This bleaching approach using enzymes resulted in 27% reduction in ClO2 dose. Ultrafiltered enzymes treated pulp samples also showed improved quality-related parameters, and Gurley porosity, burst index, breaking length, double fold, tear index, and viscosity increased by 19.05, 13.70, 8.18, 29.27, 4.41, and 13.27%, respectively. The lignin content, TDS, TSS, BOD and COD values also decreased in the effluent samples obtained after enzymatic bleaching plus 73% chemical bleaching dose. The BOD and COD values of the effluent samples improved by 23.01 and 23.66%, respectively. Thus, indicating the potential of ultrafiltered xylano-pectinolytic enzymes in reducing pollution during bleaching of wheat straw. This is the first study, mentioning the efficacy of ultrafiltered enzymes in the bleaching of wheat straw-based paper with better optical-strength-related properties and effluent characteristics.
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Lignina , Papel , Triticum/química , Endo-1,4-beta-Xilanases/química , PoligalacturonaseRESUMO
Tuberculosis infection has always been a global concern for public health, and the mortality rate has increased tremendously every year. The ability of the resuscitation Mycobacterium tuberculosis (Mtb) from the dormant state is one of the major reasons for the epidemic spread of tuberculosis infection, especially latent tuberculosis infection (LTBI). The element that encourages resuscitation, RpfB (resuscitation-promoting factors B), is mostly in charge of bringing Mtb out of slumber. This reason makes RpfB a promising target for developing tuberculosis drugs because of the effects of latent tuberculosis. Therefore, this work was executed using a computational three-level screening of the Selleckhem antibiotics database consisting of 462 antibiotics against the ligand binding region of the RpfB protein, followed by an estimation of binding free energy for ideal identification and confirmation of potential RpfB inhibitor. Subsequently, three antibiotic drug molecules, i.e., Amikacin hydrate (-66.87 kcal/mol), Isepamicin sulphate (-60.8 kcal/mol), and Bekanamycin (-46.89 kcal/mol), were selected on the basis of their binding free energy value for further computational studies in comparison to reference ligand, 4-benzoyl-2-nitrophenyl thiocyanate (NPT7). Based on the intermolecular interaction profiling, 200 ns molecular dynamic simulation (MD), post-simulation analysis and principal component analysis (PCA), the selected antibiotics showed substantial stability with the RpfB protein compared to the NPT7 inhibitor. Conclusively based on the computational results, the preferred drugs can be potent inhibitors of the RpfB protein, which can be further validated using in vivo research and in vitro enzyme inhibition to understand their therapeutic activity against tuberculosis infection.Communicated by Ramaswamy H. Sarma.
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BACKGROUND: Fractional flow reserve-computed tomography (FFR-CT) is endorsed by UK and U.S. chest pain guidelines, but its clinical effectiveness and cost benefit in real-world practice are unknown. OBJECTIVES: The purpose of this study was to audit the use of FFR-CT in clinical practice against England's National Institute for Health and Care Excellence guidance and assess its diagnostic accuracy and cost. METHODS: A multicenter audit was undertaken covering the 3 years when FFR-CT was centrally funded in England. For coronary computed tomographic angiograms (CCTAs) submitted for FFR-CT analysis, centers provided data on symptoms, CCTA and FFR-CT findings, and subsequent management. Audit standards included using FFR-CT only in patients with stable chest pain and equivocal stenosis (50%-69%). Diagnostic accuracy was evaluated against invasive FFR, when performed. Follow-up for nonfatal myocardial infarction and all-cause mortality was undertaken. The cost of an FFR-CT strategy was compared to alternative stress imaging pathways using cost analysis modeling. RESULTS: A total of 2,298 CCTAs from 12 centers underwent FFR-CT analysis. Stable chest pain was the main symptom in 77%, and 40% had equivocal stenosis. Positive and negative predictive values of FFR-CT were 49% and 76%, respectively. A total of 46 events (2%) occurred over a mean follow-up period of 17 months; FFR-CT (cutoff: 0.80) was not predictive. The FFR-CT strategy costs £2,102 per patient compared with an average of £1,411 for stress imaging. CONCLUSIONS: In clinical practice, the National Institute for Health and Care Excellence criteria for using FFR-CT were met in three-fourths of patients for symptoms and 40% for stenosis. FFR-CT had a low positive predictive value, making its use potentially more expensive than conventional stress imaging strategies.
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Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Humanos , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/terapia , Constrição Patológica , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Angiografia Coronária/métodos , Dor no Peito , Custos e Análise de Custo , Angiografia por Tomografia Computadorizada/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapiaRESUMO
This study has been conducted to assess the pulpability of ultrafiltered pectinase and xylanase in pulping of wheat straw. Best biopulping conditions were achieved using 107 and 250 IU of pectinase and xylanase, respectively, per gram of wheat straw, 180 min of treatment period, one gram: 10 m1 material to liquor ratio, 8.5 pH and 55 °C temperature. Ultrafiltered enzymatic treatment improved the pulp yield (6.18%), brightness (17.83%), along with reduced rejections (61.01%) and kappa number (16.95%) as compared to chemically synthesized pulp. Biopulping of wheat straw saved 14% alkali dose, with nearly same optical properties, as obtained under 100% alkali dose. Bio-chemically pulped samples resulted an increase in breaking length, tear index, burst index, viscosity, double fold and Gurley porosity by 6.05%, 18.64%, 26.42%, 7.94%, 21.6% and 15.38%, respectively, in comparison to control pulp samples. Bleached-biopulped samples showed an improvement in breaking length, tear index, burst index, viscosity, double fold number, and Gurley porosity by 7.39%, 3.55%, 28.82%, 9.1%, 53.66%, and 30.95% respectively. Thus, biopulping of wheat straw with ultrafiltered enzymes lowers alkali consumption and also improves the paper quality. This is the first study reporting, eco-friendly biopulping, for producing better quality wheat straw pulp, using ultrafiltered enzymes.
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This research aimed to investigate the efficiency of crude xylanase-pectinase in pulping of sugarcane bagasse. Optimum biopulping was obtained, using xylanase-pectinase dose 200-60 IU/g, bagasse/liquid ratio 1:10 and 1.0% Tween 80 concentration at 55 °C temperature, pH 8.5 and period of treatment 180 min. Treatment of sugarcane bagasse samples with these enzymes generated pulp with lower rejections (58.76%), total solids (12.64%), kappa number (47.77%), higher screened pulp yield (10.66%), along with enhanced optical and physical properties, in comparison with a chemical pulp. Bagasse biopulping resulted in a 13% decrease in alkali dose to obtain the optical and physical properties similar to those achieved under the 100% alkali dose. The breaking length, burst factor, tear index, double fold, gurley porosity and viscosity were improved by 15.19, 37.64, 2.47, 37.77, 35 and 23.17%, respectively, after bleaching treatment of biopulped samples. Thus, enzymatic pulping is an eco-friendly environmentally sustainable approach, since it reduces the use of pulping chemicals and simultaneously improves the paper quality. This is the first report, showing pulping of sugarcane bagasse, with crude xylanase-pectinase, produced by an isolate.
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In the current study, pretreatment of sugarcane bagasse has been carried out with ultrafiltered xylano-pectinolytic enzymes, before conventional chemical bleaching process. Optimized enzymatic dose (4 IU xylanase and 1.2 IU pectinase per g of oven dried pulp) and retention time (180 min) were determined on the basis of maximum decrement in kappa number (from 20.93 to 15.32), release of maximum sugars (7.4 mg/g) as well as attainment of maximum brightness (25.1% ISO), whiteness (from - 57.3 to - 41.9) and minimum yellowness (from 48.7 to 35.3) of the pulp samples. Enzymatically treated samples also showed release of phenolic, lignin and hydrophobic compounds in their filtrates. Nearly 30% decrement in the exhaustion of bleaching chemical dose was detected as compared to control samples. The physical properties such as tear index, burst index, double fold number, breaking length, gurley porosity and viscosity of enzymo-chemically treated bagasse pulp samples were improved by 6.68%, 33.86%, 22.92%, 13.43%, 17.5% and 9.64%, respectively. Additionally, a decrement of 36.75% and 28.29% in the values of BOD and COD of the effluents was also noted, which demonstrated the fact that, inclusion of enzymes in chemical based protocols of paper and pulp industries could be a highly beneficial and eco-friendly approach in upcoming decades. This is the first report mentioning the effect of ultrafiltered xylano-pectinolytic enzymes concoction on sugarcane bagasse pulp.
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Saccharum , Celulose , Papel , PoligalacturonaseRESUMO
Diagnosis and treatment of lung diseases pose serious challenges. Currently, diagnostic as well as therapeutic methods show poor efficacy toward drug-resistant bacterial infections, while chemotherapy causes toxicity and nonspecific delivery of drugs. Advanced treatment methods that cure lung-related diseases, by enabling drug bioavailability via nasal passages during mucosal formation, which interferes with drug penetration to targeted sites, are in demand. Nanotechnology confers several advantages. Currently, different nanoparticles, or their combinations, are being used to enhance targeted drug delivery. Nanomedicine, a combination of nanoparticles and therapeutic agents, that delivers drugs to targeted sites increases the bioavailability of drugs at these sites. Thus, nanotechnology is superior to conventional chemotherapeutic strategies. Here, the authors review the latest advancements in nanomedicine-based drug-delivery methods for managing acute and chronic inflammatory lung diseases.
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Pneumopatias , Nanopartículas , Humanos , Nanomedicina/métodos , Sistemas de Liberação de Medicamentos/métodos , Nanotecnologia/métodos , Preparações Farmacêuticas , Pulmão , Pneumopatias/tratamento farmacológicoRESUMO
The aim of this study was to evaluate the potential of xylanase-pectinase enzymes in bleaching of wheat straw pulp, just to cut down the toxic wastes, in order to manage the environmental pollution. The appropriate parameters of bleaching were evaluated, and best conditions were xylanase and pectinase dose of 5.0 and 1.66 IU/g of pulp, respectively, along with material to liquid ratio of 1:7.5 (g/ml), temperature 55 °C, treatment time 3 h, Tween-80 1%, and pH 8.5. The release of reducing sugar and other non-cellulosic impurities, phenolic-hydrophobic-lignin was maximum at best bleaching conditions. Prebleaching of wheat straw pulp using these enzymes showed 14.75% decline in kappa number. Enzymatic bleaching plus 100% chemical bleaching also led to 27.90% reduction in yellowness. Using this methodology, the consumption of active chlorine was reduced up to 25%, along with an increase in burst index (7.98%), tear index (3.42%), breaking length (5.30%), viscosity (11.22%), gurley porosity (12.50%), and double-fold number (23.08%), which exhibits a remarkable enhancement in all the properties of pulp treated with enzymes. Microscopic images also confirm the effectiveness of enzymatic treatment in bleaching of wheat straw pulp. BOD and COD values of effluent also decreased by 20.74 and 17.87%, respectively. This research focussing on producing better grade paper using an eco-friendly approach would certainly benefit the paper and pulp industry. This is the first report, depicting bleaching capability of xylanase-pectinase enzymes for soda-anthraquinone pulp of wheat straw.
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CelulaseRESUMO
In this study, suitability of xylano-pectinolytic enzymes in pulping of wheat straw has been explored. The suitable biopulping conditions were optimized, with xylanase dose of 400 and pectinase dose of 120 IU/g wheat straw, 1:10 (g/ml) material to liquid ratio, 55 °C temperature, 3 h treatment time, 0.75% Tween 80 and pH 8.5. Enzymatic pretreatment efficiently increased the pulpability of wheat straw, generated pulp with higher yield, lower kappa number (15.67%) and rejections (59.65%) in comparison with chemical pulp. The brightness of pretreated wheat straw pulp with enzyme was 16.04% higher than that of the non-enzyme treated wheat straw pulp. The biopulping resulted in 12% reduction of pulping chemicals along with more residual alkali content, in order to achieve similar optical and chemical properties as obtained by 100% chemically treated pulp. Physical properties of pulp also improved after enzymatic pretreatment, increasing burst index (26.50%), tear index (18.22%) and breaking length (5.56%). The enzyme plus chemical (88% pulping chemicals) treated pulp showed improvement in brightness and whiteness, with reduction in yellowness at all bleaching stages. In comparison with chemically bleached pulp, biopulp with reduced alkali dose (88%) had higher breaking length (6.63%), double fold number (51.28%), tear index (2.83%), burst index (24.31%), along with increased viscosity (6.12%) and Gurley porosity (27.50%). These results clearly suggest that biopulping of wheat straw with xylano-pectinolytic enzymes can reduce chemical loading during soda-anthraquinone pulping and also improve the quality of paper. This is the first report demonstrating the biopulping of wheat straw using crude xylano-pectinolytic enzymes.
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Endo-1,4-beta-Xilanases , Triticum , Álcalis , Cor , Papel , PoligalacturonaseRESUMO
In this study, zymographic analysis for xylanase and pectinase enzymes has been carried out using agrowaste residues, wheat bran and citrus peel as well as their extracts. Isozymic forms of xylanase as well as pectinase enzyme displayed comparable zymographic bands onto agar petriplates containing either commercial substrates (xylan and pectin), agrowaste-based substrates (wheat bran and citrus peel), or polysaccharides extracted from these agrowastes (crude xylan and pectin extracted from wheat bran and citrus peel, respectively), indicating the fact that agro residues and their extracts can be utilized as a substitute of cost-intensive commercial substrates, xylan and pectin for zymographic analysis. This is the first report revealing the zymographic analysis of xylano-pectinolytic enzymes using agro-based solid residues particles or polysaccharides extracted from agro-based residues.
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Pectinas/química , Poligalacturonase/análise , Resíduos , Xilanos/química , Xilosidases/análise , Pectinas/metabolismo , Poligalacturonase/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Xilanos/metabolismo , Xilosidases/metabolismoRESUMO
The aim of this study was to enhance the production of xylano-pectinolytic enzymes concurrently and also to reduce the fermentation period. In this study, the effect of agro-residues extract-based inoculum on yield and fermentation time of xylano-pectinolytic enzymes was studied. Microbial inoculum and fermentation media were supplemented with xylan and pectin polysaccharides derived from agro-based residues. Enzymes production parameters were optimized through two-stage statistical design approach. Under optimized conditions (temperature 37°C, pH 7.2, K2 HPO4 0.22%, MgSO4 0.1%, gram flour 5.6%, substrate: moisture ratio 1:2, inoculum size 20%, agro-based crude xylan in production media 0.45%, and agro-based crude xylan-pectin in inoculum 0.13%), nearly 28,255 ± 565 and 9,202 ± 193 IU of xylanase and pectinase, respectively, were obtained per gram of substrate in a time interval of 6 days only. The yield of both xylano-pectinolytic enzymes was enhanced along with a reduction of nearly 24 h in fermentation time in comparison with control, using polysaccharides extracted from agro-residues. The activity of different types of pectinase enzymes such as exo-polymethylgalacturonase (exo-PMG), endo-PMG, exo-polygalacturonase (exo-PG), endo-PG, pectin lyase, pectate lyase, and pectin esterase was obtained as 1,601, 12.13, 5637, 24.86, 118.62, 124.32, and 12.56 IU/g, respectively, and was nearly twofold higher than obtained for all seven types in control samples. This is the first report mentioning the methodology for enhanced production of xylano-pectinolytic enzymes in short solid-state fermentation cycle using agro-residues extract-based inoculum and production media.
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Enzimas/biossíntese , Fermentação , Técnicas de Síntese em Fase Sólida , Xilosidases/biossíntese , Enzimas/química , Concentração de Íons de Hidrogênio , Pectinas/farmacologia , Poligalacturonase/biossíntese , Poligalacturonase/química , Polissacarídeo-Liases/biossíntese , Polissacarídeo-Liases/química , Temperatura , Xilanos/farmacologia , Xilosidases/química , Xilosidases/classificaçãoRESUMO
In this study, screening and isolation of xylano-cellulolytic enzymes producing positive microbes from termitarium and termite gut microbiome were done using cost-effective agricultural wastes. The enrichment of xylano-cellulolytic microbes was done in three steps using wheat bran and waste paper. The qualitative screening of xylanase and cellulase producing micro-organisms was done on nutrient agar plates containing wheat bran and waste paper, respectively. Xylanase and cellulase positive colonies were analysed by observing the zone of substrate (wheat bran and waste paper) hydrolysis around the colonies. A total of 30 bacterial isolates were obtained from termite gut and termitarium, respectively. Xylan and cellulose degrading potential of the positive isolates was also quantitatively estimated using agro-wastes-based medium. All the bacterial isolates displayed cellulase and xylanase activities in the range of 0.45-6.80 and 51-380 IU/ml, respectively. This is the first report mentioning the isolation of xylano-cellulolytic microbes from termite gut and termitarium using very simple cost-effective methodology.
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The effect of ultrafiltered xylanase-pectinase concoction produced simultaneously by a bacterial isolate using agro-waste-based media was assessed in prebleaching of plywood waste pulp. Ultrafiltered enzymes caused 12.5% reduction in kappa number at reduced enzyme dose of xylanase-pectinase (4.0-0.8 IU) per gram of pulp under optimized conditions at pH 8.5, temperature 55 °C, and treatment period of 2 h. Using this methodology, amount of Cl2-ClO2 consumption can be reduced up to 30 and 28.86%. Significant improvement in physical and optical properties of pulp was obtained along with an additional reduction in BOD and COD values up to 18.13 and 21.66% using this novel biodelignification approach. This is the first report showing the advantages of using ultrafiltered xylanase-pectinase over crude enzymes in enhancing the bleaching capacity of pulp. This study focussing on the development of good quality paper with less pollution generating strategy will definitely prove a boon for industries.
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Indian mustard seeds were defatted by distillation with hexane and the residue extracted with methanol was analyzed for potential antioxidants; ascorbate, riboflavin, and polyphenols. Gallic acid (129.796 µg), caffeic acid (753.455 µg), quercetin (478.352 µg) and kaempferol (48.060 µg)/g dry seeds were identified by HPLC analysis of the extract. DPPH free radical scavenging activity and protection of lipids, proteins and DNA against metal induced oxidation was examined. Defatted mustard seed remnant had excellent free radical scavenging activity and protects biomolecules with IC50 value 2.0-2.25 mg dry seed weight. Significant content of polyphenols in methanol extract of defatted seeds accounts for high antioxidant potential. We are the first to report the detailed analysis of antioxidant composition and protection of biomolecules against oxidative damage by methanol extract of mustard seed remnant after oil extraction.