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Carotenoids are a diverse group of pigments known for their broad range of biological functions and applications. This study delves into multifaceted potential of carotenoids extracted from Haloferax larsenii NCIM 5678 previously isolated from Pachpadra Salt Lake in Rajasthan, India. H. larsenii NCIM 5678 was able to grow up to OD600 1.77 ± 0.03 with carotenoid concentration, 3.3 ± 0.03 µg/ml. The spectrophotometric analysis of carotenoid extract indicated the presence of three-fingered peak (460, 490 and 520 nm) which is a characteristic feature of bacterioruberin and its derivatives. The bacterioruberin was purified using silica gel column chromatography and thin layer chromatography. The carotenoid extract showed 12.3 ± 0.09 mm zone of growth inhibition with a minimum inhibitory concentration 546 ng/ml against indicator strain, H. larsenii HA4. The percentage antioxidant activity of carotenoid was found to be 84% which was higher as compared to commercially available ascorbic acid (56.74%). Thus, carotenoid extract from H. larsenii NCIM 5678 possesses unique attributes with compelling evidence of antimicrobial and antioxidant potential for the development of novel pharmaceuticals and nutraceuticals.
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Antioxidantes , Carotenoides , Haloferax , Lagos , Carotenoides/química , Carotenoides/metabolismo , Lagos/microbiologia , Antioxidantes/farmacologia , Antioxidantes/química , Haloferax/metabolismoRESUMO
2D graphene the most investigated structures from nanocarbon family studied in the last three decades. It is projected as an excellent material useful for quantum computing, artificial intelligence, and next generation advanced technologies. Graphene exists in several forms and its extraordinary thermal, mechanical, and electronic properties, principally depend on the kind of perfection of the hexagonal atomic lattice. Defects are always considered as undesired components but certain defects in graphene could be an asset for electrochemistry and quantum electronics due to the engineered electronclouds and quantum tunnelling. The authors carefully discuss the Stone-Wales imperfections in graphene and its derivatives comprehensively. A specific emphasis is focused on the experimental and theoretical aspects of the Stone-Wales defects in graphene with respect to structure-property relationships. The corroboration of extrinsic defects like external atomic doping, functionalization, edge distortion in the graphene consisting of Stone-Wales imperfections, which are very significant in designing graphene-based electronic devices, are summarized.
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OBJECTIVE: To assess healthcare costs and healthcare resource utilization (HCRU) among adult patients who newly initiated erenumab in the United States. METHODS: This retrospective, non-interventional analysis included adult patients (aged ≥18 years) newly initiating erenumab and who had three consecutive monthly claims for erenumab (11/1/2017-9/1/2019) from the Komodo Health database. Outcomes included migraine-related and all-cause costs, use of other preventive/acute migraine medications, and HCRU. All outcomes were compared during the 180-day pre- versus the 180-day post-index periods. Cost outcomes were also assessed for longer periods including post-index Days 91-270 and monthly mean post-index costs for the longest time of continuous insurance enrollment. RESULTS: Overall, 1839 patients with migraine were included for analysis. Compared to the 180-day pre-index period, an increase in total migraine-related costs (+$2639; p < 0.0001), migraine-related prescription costs (+$3435, p < 0.0001), all-cause total costs (+$2977; p < 0.001), and all-cause prescription costs (+$4102; p < 0.0001) were observed during the 180-day post-index period after adjusting for covariates. Conversely, reduction in migraine-related medical costs (-$896; p < 0.0001), and significantly lower odds of migraine-related emergency room visits (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.44-0.82; p = 0.001), migraine-related office visits (OR 0.58, 95% CI 0.53-0.64; p < 0.0001), and migraine-related neurologist visits (OR 0.69, 95% CI 0.63-0.75; p < 0.0001) were observed during the 180-days post-index period. There were significant decreases in the odds of having overall preventive migraine medications (OR 0.81, 95% CI 0.75-0.87; p < 0.0001), acute-migraine medications (OR 0.92, 95% CI 0.85-1.00; p = 0.038), and triptan (OR 0.79, 95% CI 0.73-0.85; p < 0.0001) during the 180-day post-index period. Sensitivity analyses on cost outcomes found no statistically significant differences in pre-index migraine-related costs compared to post-index migraine-related costs when assessing longer post-index follow-up periods. CONCLUSION: Initiation of therapy with a novel treatment is often associated with an increase in overall healthcare costs due to the entrance costs associated with novel therapy. For a chronic condition such as migraine, cost versus health benefits should be evaluated over a long period (e.g., ≥2 years) to better understand the true benefits of therapy. Data from this study suggest that the entrance cost for erenumab, the primary driver of the high post-index prescription costs gets mitigated by reduced medical costs over long-term follow-up. The results indicate better disease management in adult patients with migraine, which should be an important consideration for both patients and payors, as these findings have shown an offset between migraine-related prescription and medical costs.
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Custos de Cuidados de Saúde , Transtornos de Enxaqueca , Adulto , Humanos , Estados Unidos , Adolescente , Estudos Retrospectivos , Transtornos de Enxaqueca/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
Phytases are important enzymes used for eliminating the anti-nutritional properties of phytic acid in food and feed ingredients. Phytic acid is major form of organic phosphorus stored during seed setting. Monogastric animals cannot utilize this phytate-phosphorus due to lack of necessary enzymes. Therefore, phytic acid excretion is responsible for mineral deficiency and phosphorus pollution. Phytases have been reported from diverse microorganisms, however, fungal phytases are preferred due to their unique properties. Aspergillus species are the predominant producers of phytases and have been explored widely as compared to other fungi. Solid-state fermentation has been studied as an economical process for the production of phytases to utilize various agro-industrial residues. Mixed substrate fermentation has also been reported for the production of phytases. Physical and chemical parameters including pH, temperature, and concentrations of media components have significantly affected the production of phytases in solid state fermentation. Fungi produced high levels of phytases in solid state fermentation utilizing economical substrates. Optimization of culture conditions using different approaches has significantly improved the production of phytases. Fungal phytases are histidine acid phosphatases exhibiting broad substrate specificity, are relatively thermostable and protease-resistant. These phytases have been found effective in dephytinization of food and feed samples with concomitant liberation of minerals, sugars and soluble proteins. Additionally, they have improved the growth of plants by increasing the availability of phosphorus and other minerals. Furthermore, phytases from fungi have played an important roles in bread making, semi-synthesis of peroxidase, biofuel production, production of myo-inositol phosphates and management of environmental pollution. This review article describes the production of fungal phytases in solid state fermentation and their biotechnological applications.
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6-Fitase , Animais , 6-Fitase/química , 6-Fitase/metabolismo , Fermentação , Ácido Fítico/metabolismo , Fósforo , MineraisRESUMO
Probiotics have been considered as an economical and safe alternative for the treatment of a large number of chronic diseases and improvement of human health. They are known to modulate the host immunity and protect from several infectious and non-infectious diseases. The colonization, killing of pathogens and induction of host cells are few of the important probiotic attributes which affect several functions of the host. In addition, prebiotics and non-digestible food substances selectively promote the growth of probiotics and human health through nutrient enrichment, and modulation of gut microbiota and immune system. This review highlights the role of probiotics and prebiotics alone and in combination (synbiotics) in the modulation of immune system, treatment of infections, management of inflammatory bowel disease and cancer therapy. KEY POINTS: ⢠Probiotics and their derivatives against several human diseases. ⢠Prebiotics feed probiotics and induce several functions in the host. ⢠Discovery of novel and biosafe products needs attention for human health.
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Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Probióticos , Simbióticos , Humanos , PrebióticosRESUMO
The interaction of antimicrobial peptides with membrane lipids plays a major role in numerous physiological processes. In this study, polydiacetylene (PDA) vesicles were synthesized using 10, 12-tricosadiynoic acid (TRCDA) and 1, 2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). These vesicles were applied as artificial membrane biosensor for the detection of plantaricin LD1 purified from Lactobacillus plantarum LD1. Plantaricin LD1 (200 µg/mL) was able to interact with PDA vesicles by changing the color from blue to red with colorimetric response 30.26 ± 0.59. Nisin (200 µg/mL), used as control, also changed the color of the vesicles with CR% 50.56 ± 0.98 validating the assay. The vesicles treated with nisin and plantaricin LD1 showed increased infrared absorbance at 1411.46 and 1000-1150 cm-1 indicated the interaction of bacteriocins with phospholipids and fatty acids, respectively suggesting membrane-acting nature of these bacteriocins. Further, microscopic observation of bacteriocin-treated vesicles showed several damages indicating the interaction of bacteriocins. These findings suggest that the PDA vesicles may be used as bio-mimetic sensor for the detection of bacteriocins produced by several probiotics in food and therapeutic applications.
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Peptídeos Antimicrobianos/análise , Bacteriocinas/análise , Colorimetria/métodos , Polímero Poliacetilênico/química , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/isolamento & purificação , Bacteriocinas/química , Bacteriocinas/isolamento & purificação , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Dimiristoilfosfatidilcolina/química , Ácidos Graxos Insaturados/química , Lactobacillus plantarum/química , Membranas Artificiais , Nisina/química , Espectroscopia de Infravermelho com Transformada de Fourier , UltrafiltraçãoRESUMO
BACKGROUND: Research indicates that Helicobacter pylori can inflict severe histological damage through the modulation of host-related genes. The current study investigated the effect of H. pylori genotypes in the outcome of disease, and the expression of anti-apoptotic related genes, COX-1, COX-2, and iNOS genes in benign, pre-malignant, and malignant lesions of gastric carcinogenesis. MATERIALS AND METHODS: Tissue samples from H. pylori positive patients were graded based on the genotype of the infected H. pylori strain. Expression of COX-1, COX-2 and iNOS was assessed using a combination of real-time PCR and immunohistochemistry. RESULTS: Gene expression studies confirmed that COX-2 and iNOS expression was highly and selectively induced in epithelium with premalignant changes such as atrophic conditions, metaplasia and dysplasia, suggesting an important role of these genes in the sequence to gastric carcinoma of the intestinal type. Furthermore, the expression of COX-2 and iNOS was also dependent on the genotype of H. pylori and subjects with genotype-1 exhibited significantly higher expressions of COX-2 and iNOS compared to other genotypes. Comparison of the expression levels among infected and uninfected individuals demonstrated significant difference in the expression pattern of COX-2 gene whereas iNOS expression was found only in subjects infected H. pylori (pâ¯<â¯0.001). Immunohistochemical staining showed 1.5619 folds higher propensity of COX-2 and 3.2941 folds higher intensity of iNOS expression in subjects infected with H. pylori genotype 1. CONCLUSION: The up-regulation of COX-2 and iNOS was associated with the genotype of the H. pylori strain and the presence of certain genotype may greatly affect early events during carcinogenesis.
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Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Expressão Gênica , Infecções por Helicobacter/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Adenocarcinoma , Adulto , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Mucosa Gástrica/patologia , Gastrite , Gastrite Atrófica , Genótipo , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Imuno-Histoquímica , Metaplasia , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/patologia , Regulação para CimaRESUMO
AIMS: To understand the bactericidal action of enterocin LD3 against Gram-negative bacteria. METHODS AND RESULTS: Minimum inhibitory concentration (MIC) of enterocin LD3 against Micrococcus luteus MTCC 106 and Escherichia coli NCDC 135 was 80 and 112 µg ml-1 , and minimum bactericidal concentration (MBC) was 128 and 180 µg ml-1 , respectively. The efflux of potassium ion (K+ ) was 14 and 13 ppm and electrical conductivity 10·5 and 8·3 mS cm-1 in cell-free supernatant of MIC-treated cells of M. luteus and E. coli respectively. The increased absorbance (OD260/280 ) 0·422/0·260 and 0·110/0·075 in the bacteriocin-treated cells of M. luteus MTCC 106 and E. coli, NCDC 135, respectively, suggested the release of nucleic acids and proteins. The higher infrared absorbance at 1451·82 and ~1094·30 cm-1 further suggested its interaction with cell membrane and nucleic acids of the target bacteria. The interaction of bacteriocin with nucleic acids was also confirmed using gel retardation assay. Transmission electron microscopy of the bacteriocin-treated cells revealed disruption of cell membrane and leakage of cytoplasmic contents. CONCLUSIONS: Enterocin LD3 demonstrates bactericidal activity against Gram-negative bacteria interacting with cell membrane and nucleic acids. SIGNIFICANCE AND IMPACT OF THE STUDY: The study discloses the possible mechanism of action of enterocin LD3 against Gram-negative bacteria which is a rare phenomenon.
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Antibacterianos/farmacologia , Streptococcus faecium ATCC 9790/química , Bactérias Gram-Negativas/efeitos dos fármacos , Íons/metabolismo , Transporte Biológico/efeitos dos fármacos , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Membrana Celular/efeitos dos fármacos , Bactérias Gram-Negativas/metabolismo , Testes de Sensibilidade Microbiana , Ácidos Nucleicos/metabolismoRESUMO
Bacteriocin LB44 was purified from cell-free supernatant (CFS) of Pediococcus pentosaceus LB44 using activity-guided chromatography techniques. It was stable up to 121⯰C, pH 2.0-6.0, sensitive to proteinase K, papain and trypsin, and retained complete activity in the presence of organic solvents tested. The molecular weight of bacteriocin was â¼6â¯kDa and initial ten amino acid residues (GECGMCXECG) suggested a new compound. The loss in viable cell count and K+ ion efflux of target cells of Micrococcus luteus suggested bactericidal activity. The cell membrane of bacteriocin-treated cells was found to be ruptured which was further confirmed by Fourier Transform Infrared (FTIR) analysis suggesting interaction of bacteriocin with phospholipids in cell membrane. It showed broad host-range and inhibited the growth of Lactobacillus delbrueckii NRRL B-4525, L. plantarum NRRL B-4496, L. acidophilus NRRL B-4495, Enterococcus hirae LD3, Weissella confusa LM85, Staphylococcus aureus, Salmonella typhi ATCC 13311, Serratia marcescens ATCC 27137, Pseudomonas aeruginosa ATCC 27853, Proteus vulgaris ATCC 29905, Haloferax larsenii HA1, HA3, HA8, HA9 and HA10. These properties suggested a new bacteriocin from soil isolate P. pentosaceus LB44 which may offers possible applications in food-safety and therapeutics.
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Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bacteriocinas/isolamento & purificação , Bacteriocinas/farmacologia , Pediococcus pentosaceus/química , Sequência de Aminoácidos , Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , Bacteriocinas/química , Microbiologia de Alimentos , Halobacteriaceae/efeitos dos fármacos , Humanos , Microbiologia do SoloRESUMO
Haloferax larsenii HA3 was able to grow optimally in HS medium containing 15% NaCl, at pH 7.2 and 42 °C in aerobic conditions. Strain HA3 was found to be round shape, Gram-negative, catalase-positive, sensitive to bile acid, and resistant to chloramphenicol, and could not utilize arginine. The lipid profile revealed the presence of glycerol diether moiety (GDEM) suggesting Haloarchaea characteristics. Phylogenetic analysis based on 16S rRNA gene sequence similarities showed that it was closely related to H. larsenii ZJ206. Interestingly, strain HA3 was found to produce halocin HA3 which was purified using ultrafiltration and chromatography. It was found to be stable up to 80 °C, pH 2.0-10.0, organic solvents, surfactants, and detergents tested. However, the activity of halocin HA3 was completely reduced in the presence of proteinase K and trypsin. It was found to be halocidal against H. larsenii HA10, rupturing cell boundary and leading to cell death. The molecular weight of halocin HA3 was found to be ~13 kDa and MALDI-TOF MS/MS analysis suggested no homology with known halocins. The N-terminal ten amino-acid residues, NH2MNLGIILETN-COOH, suggested a new/novel halocin. These properties of halocin HA3 may be applicable for control of Haloarchaea in environments and salted foods.
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Proteínas Arqueais/química , Bacteriocinas/metabolismo , Haloferax/metabolismo , Proteínas Arqueais/metabolismo , Bacteriocinas/química , Bacteriocinas/genética , Fermentação , Estabilidade Proteica , ProteóliseRESUMO
Haloarchaea grow in the extreme environment, such as high salt concentration, and secrete antimicrobial peptides known as halocins. Identification of Haloferax larsenii strain HA1 was carried out using biochemical and molecular methods. Strain HA1 was found as a strict aerobe, catalase positive and Gram negative. It was able to grow optimally at 15 % NaCl (w/v), 42 °C and pH 7.2. Strain HA1 was sensitive to bile acid, was resistant to chloramphenicol and could not utilize arginine. Halocin, produced by strain HA1, was stable up to 100 °C and in a pH range of 5.0-9.0. Antimicrobial activity was not affected by organic solvents, surfactants and detergents, but it was completely lost in the presence of proteinase K, suggesting proteinaceous nature of the compound. It was halocidal against indicator strain Hfx. larsenii HA10. The molecular weight of halocin HA1 was found to be ~14 kDa. These properties of halocin HA1 may be applicable to the preservation of salted foods.
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Haloferax/classificação , Haloferax/metabolismo , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/metabolismo , Bactérias Aeróbias/química , Bactérias Aeróbias/classificação , Bactérias Aeróbias/isolamento & purificação , Bactérias Aeróbias/metabolismo , Catalase/metabolismo , Haloferax/química , Haloferax/isolamento & purificação , Índia , Peso Molecular , Plantas Tolerantes a Sal/química , Plantas Tolerantes a Sal/classificação , Plantas Tolerantes a Sal/metabolismoRESUMO
Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics.
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Antibacterianos/química , Antibacterianos/farmacologia , Bacteriocinas/química , Bacteriocinas/farmacologia , Hidrocarbonetos Aromáticos com Pontes/química , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Escherichia coli O157/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Pediocinas , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacologia , Salmonella enteritidis/efeitos dos fármacosRESUMO
BACKGROUND: Development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents. METHODS: Inspired by their ethnobotanical reputation for being effective against febrile diseases, antiplasmodial potential of ethyl acetate extracts (EAE) and methanol extracts (ME) of 17 medicinal plants collected from the Eastern Ghats of South India and Buchpora, North India were explored against Plasmodium falciparum in vitro using the SYBR Green assay. The results were validated both by confirmation that the fall in fluorescence signal was not due to quenching effects mediated by phytochemical extracts and by Giemsa-stained microscopy. RESULTS: Using EAE or ME, promising antiplasmodial activity (IC50 Pf3D7 ≤ 20 µg/ml), was seen in Aerva lanata (Whole aerial parts-EAE), Anisomeles malabarica (Leaf-EAE), Anogeissus latifolia (bark-EAE), Cassia alata (leaves-EAE), Glycyrrhiza glabra (root-EAE), Juglans regia (seed-ME), Psidium guajava (leaf-ME and EAE) and Solanum xanthocarpum (Whole aerial parts-EAE). EAEs from leaves of Couroupita guianensis, Euphorbia hirta, Pergularia daemia, Tinospora cordifolia and Tridax procumbens as also ME from Ricinus communis (leaf and seed) showed good antiplasmodial activity (Pf 3D7 IC50 21 - 40 µg/ml). Moderate activity (Pf 3D7 IC50: 40-60 µg/mL) was shown by the leaf EAEs of Cardiospermum halicacabum, Indigofera tinctoria and Ricinus communis while the remaining extracts showed marginal (Pf 3D7 IC50 60 to >100 µg/ml) activities. The promising extracts showed good resistance indices (0.41 - 1.4) against the chloroquine resistant INDO strain of P. falciparum and good selectivity indices (3 to > 22.2) when tested against the HeLa cell line. CONCLUSION: These results provide validity to the traditional medicinal usage of some of these plants and further make a case for activity-guided purification of new pharmacophores against malaria.
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Antimaláricos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Eritrócitos/parasitologia , Células HeLa , Humanos , Índia , Extratos Vegetais/toxicidadeRESUMO
Plantaricin LD1 was purified from a potential probiotic strain, Lactobacillus plantarum LD1 previously isolated from indigenous food, Dosa. In this study, we have performed a detailed mechanism of action of plantaricin LD1 against Escherichia coli ATCC 25922 considering Micrococcus luteus MTCC 106 as control. The plantaricin LD1 showed a minimum inhibitory concentration (MIC) of 34.57 µg/mL and a minimum bactericidal concentration (MBC) of 138.3 µg/mL against M. luteus MTCC 106, whereas MIC 69.15 µg/mL and MBC 276.6 µg/mL were found against E. coli ATCC 25922. The efflux of potassium ions, dissipation of membrane potential (∆ψ), and transmembrane pH gradient (∆pH) of plantaricin LD1-treated cells suggested the membrane-acting nature of plantaricin LD1. Plantaricin LD1 also caused degradation of the genomic DNA of the target strains tested. The cell killing was confirmed by staining with propidium iodide and visualized under light and electron microscopes. The bacteriocin-treated cells were found to be ruptured, swollen, and elongated. Thus, the findings indicate plantaricin LD1 kills E. coli ATCC 25922 by interacting with the cell membrane resulting in the efflux of intracellular contents and also causing degradation of nucleic acids leading to cell death.
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Aim: To compare the efficacy of erenumab versus rimegepant as preventive treatment for patients with episodic and chronic migraine using an anchor-based matching-adjusted indirect comparison. Methods: Patients from two phase II/III trials for erenumab (NCT02066415 and NCT02456740) were pooled and weighted to match on the baseline effect modifiers (age, sex, race, baseline monthly migraine days [MMDs], and history of chronic migraine [CM]) reported in the phase II/III trial for rimegepant (NCT03732638). Four efficacy outcomes were compared between the two erenumab regimens (70 mg and 140 mg) and rimegepant, including changes in MMDs from baseline to month 1 and month 3, changes in Migraine-Specific Quality of Life Questionnaire role function - restrictive domain score from baseline to month 3, and change in disability from baseline to Month 3. Results: Compared with rimegepant, erenumab 70 mg was associated with a statistically significant reduction in MMDs at month 3 (-0.90 [-1.76, -0.03]; p = 0.042) and erenumab 140 mg was associated with statistically significant reductions in MMDs at month 1 (-0.94 [-1.70, -0.19]; p = 0.014) and month 3 (-1.28 [-2.17, -0.40]; p = 0.005). The erenumab regimens also had numerical advantages over rimegepant for other efficacy outcomes. Conclusion: In the present study, we found that erenumab had a more favorable efficacy profile than rimegepant in reducing MMDs at month 1 and month 3 for migraine prevention. These results may help with decision-making in clinical practice and can be further validated in future clinical trials or real-world studies.
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Anticorpos Monoclonais Humanizados , Transtornos de Enxaqueca , Piridinas , Qualidade de Vida , Humanos , Piperidinas/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controleRESUMO
Spray-dried niobium oxide coated with chitosan-activated carbon (NIC) was synthesized and used to remove doxorubicin hydrochloride and crystal violet from aqueous solutions under different parameters such as solution pH (2, 4, 6, and 8), contact time (1 to 9 h), initial concentration (20 to 200 mg L-1), and competing ions (0.1 M of CaCl2 and NaCl). The addition of 5 % chitosan-activated carbon to the matrix of niobium oxide slightly increased the specific surface area from 26 to 30 m2 g-1, with the introduction of a carboxylic functional group. This led to an increase in the amount of adsorbed doxorubicin hydrochloride (DOH) from 30 to 44 mg g-1 and that of crystal violet (CV) from 15 to 32 mg g-1 from the initial respective 100 mg L-1 at pH 8. The data from the concentration study fitted into Liu isotherm having adsorption capacity of 128 and 57 mg g-1 for DOH and CV respectively, while pseudo first and second order are more suitable for adsorption kinetics. The additional functional groups on the IR spectrum of NIC after the adsorption of DOH and CV confirmed the interaction between NIC and the adsorbates' molecules. The mechanism of adsorption was supported by DFT calculations.
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Quitosana , Doxorrubicina , Violeta Genciana , Nióbio , Quitosana/química , Doxorrubicina/química , Adsorção , Nióbio/química , Violeta Genciana/química , Concentração de Íons de Hidrogênio , Carvão Vegetal/química , Cinética , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Teoria da Densidade Funcional , Óxidos/química , Água/química , Soluções , Purificação da Água/métodosRESUMO
The use of microorganisms as beneficial crops for human and animal health has been studied for decades, and these microorganisms have been in practical use for quite some time. Nowadays, in addition to well-known examples of beneficial properties of lactic acid bacteria, bifidobacteria, selected Bacillus spp., and yeasts, there are several other bacteria considered next-generation probiotics that have been proposed to improve host health. Aquaculture is a rapidly growing area that provides sustainable proteins for consumption by humans and other animals. Thus, there is a need to develop new technologies for the production practices associated with cleaner and environment-friendly approaches. It is a well-known fact that proper selection of the optimal probiotics for use in aquaculture is an essential step to ensure effectiveness and safety. In this critical review, we discuss the evaluation of host-specific probiotics in aquaculture, challenges in using probiotics in aquaculture, methods to improve the survival of probiotics under different environmental conditions, technological approach to improving storage, and delivery along with possible negative consequences of using probiotics in aquaculture. A critical analysis of the identified challenges for the use of beneficial microbes in aquaculture will help in sustainable aquafarming, leading to improved agricultural practices with a clear aim to increase protein production.
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The magnitude of variations in the level of circulating mitochondrial (cir-mtDNA) and nuclear DNA (cir-ncDNA) in different diseases has indicated the need for investigating a discriminative approach for evaluating their diagnostic significance. This study reports a typical in-house process for extracting both types of cir-DNAs from a single plasma sample and assessed their usefulness in discriminating type 2 diabetes mellitus patients from healthy individuals to eliminate the prevailing dispute about their discriminative role and improve their diagnostic value. This approach offers a more precise and valuable tool for distinguishing the impact of cir-mtDNA from cir-ncDNA in diagnostic implications.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Patologia Molecular , Mitocôndrias/genética , DNA Mitocondrial/genéticaRESUMO
In order to prevent the growth of pathogens in food, bacteriocins produced by various probiotic lactic acid bacteria have been recognized as potential substitutes of chemical preservatives. In this study, enterocin LD3 was purified from the cell-free supernatant of a food isolate, Enterococcus hirae LD3 using multistep chromatography. In the fruit juice, lethal concentration (LC50) of enterocin LD3 was found to be 260 µg/mL against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The cells treated with enterocin LD3 were red colour indicating dead cells after propidium iodide staining, while untreated cells were found blue after staining with 4', 6-diamidino-2-phenylindole. The mechanism of cell killing was analyzed using infrared spectrum of cells treated with enterocin LD3 which was found altered in the range of 1,094.30 and 1,451.82 cm-1 corresponding to nucleic acids and phospholipids, respectively. The morphology of target cells were severely ruptured and lysed as observed under electron microscopy. Thus, the present study suggested that enterocin LD3 showed bactericidal activity against Salm. enterica subsp. enterica serovar Typhimurium ATCC 13311 and may be applied as a bio-preservative for the safety of fruit juices.
RESUMO
The slow kinetics of the oxygen evolution reaction (OER) is one of the significant reasons limiting the development of electrochemical hydrolysis. Doping metallic elements and building layered structures have been considered effective strategies for improving the electrocatalytic performance of the materials. Herein, we report flower-like nanosheet arrays of Mn-doped-NiMoO4/NF (where NF is nickel foam) on nickel foam by a two-step hydrothermal method and a one-step calcination method. The doping manganese metal ion not only modulated the morphologies of the nickel nanosheet but also altered the electronic structure of the nickel center, which could be the result of superior electrocatalytic performance. The Mn-doped-NiMoO4/NF electrocatalysts obtained at the optimum reaction time and the optimum Mn doping showed excellent OER activity, requiring overpotentials of 236 mV and 309 mV to drive 10 mA cm-2 (62 mV lower than the pure NiMoO4/NF) and 50 mA cm-2 current densities, respectively. Furthermore, the high catalytic activity was maintained after continuous operation at a current density of 10 mA cm-2 of 76 h in 1 M KOH. This work provides a new method to construct a high-efficiency, low-cost, stable transition metal electrocatalyst for OER electrocatalysts by using a heteroatom doping strategy.