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1.
Gut ; 73(5): 751-769, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38331563

RESUMEN

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.


Asunto(s)
Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Ratones , Animales , Enfermedad Pulmonar Obstructiva Crónica/etiología , Pulmón/metabolismo , Pulmón/patología , Neumonía/etiología , Inflamación/metabolismo , Carbohidratos/farmacología
2.
PLoS Pathog ; 16(5): e1008342, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32365117

RESUMEN

Chitinases are important enzymes that contribute to the generation of carbon and nitrogen from chitin, a long chain polymer of N-acetylglucosamine that is abundant in insects, fungi, invertebrates and fish. Although mammals do not produce chitin, chitinases have been identified in bacteria that are key virulence factors in severe respiratory, gastrointestinal and urinary diseases. However, it is unclear how these enzymes are able to carry out this dual function. Legionella pneumophila is the causative agent of Legionnaires' disease, an often-fatal pneumonia and its chitinase ChiA is essential for the survival of L. pneumophila in the lung. Here we report the first atomic resolution insight into the pathogenic mechanism of a bacterial chitinase. We derive an experimental model of intact ChiA and show how its N-terminal region targets ChiA to the bacterial surface after its secretion. We provide the first evidence that L. pneumophila can bind mucins on its surface, but this is not dependent on ChiA. This demonstrates that additional peripheral mucin binding proteins are also expressed in L. pneumophila. We also show that the ChiA C-terminal chitinase domain has novel Zn2+-dependent peptidase activity against mammalian mucin-like proteins, namely MUC5AC and the C1-esterase inhibitor, and that ChiA promotes bacterial penetration of mucin gels. Our findings suggest that ChiA can facilitate passage of L. pneumophila through the alveolar mucosa, can modulate the host complement system and that ChiA may be a promising target for vaccine development.


Asunto(s)
Quitinasas/metabolismo , Legionella pneumophila/metabolismo , Acetilglucosamina/metabolismo , Proteínas Bacterianas/metabolismo , Quitina/metabolismo , Quitinasas/fisiología , Regulación Bacteriana de la Expresión Génica/genética , Enfermedad de los Legionarios/metabolismo , Metales , Mucina-1/metabolismo , Mucinas/metabolismo , Proteolisis , Relación Estructura-Actividad , Factores de Virulencia/metabolismo
3.
Allergy ; 76(3): 714-734, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32762040

RESUMEN

The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a "poor" diet or protection against disease with a "healthy" diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.


Asunto(s)
Microbioma Gastrointestinal , Enfermedades del Sistema Inmune , Microbiota , Dieta , Tracto Gastrointestinal , Humanos
4.
J Fish Dis ; 44(10): 1619-1637, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34237181

RESUMEN

Anti-nutritional factors in dietary components can have a negative impact on the intestinal barrier. Here, we present soya bean-induced changes in the intestine of juvenile zebrafish and the effect of yeast ß-glucan through a transcriptomic approach. The inclusion of soya bean meal affected the expression of several intestinal barrier function-related genes like arl4ca, rab25b, rhoub, muc5ac, muc5d, clcn2c and cltb in zebrafish. Several metabolic genes like cyp2x10.2, cyp2aa2, aldh3a2b, crata, elovl4, elovl6, slc51a, gpat2 and ATP-dependent peptidase activity (lonrf, clpxb) were altered in the intestinal tissue. The expression of immune-related genes like nlrc3, nlrp12, gimap8, prdm1 and tph1a, and genes related to cell cycle, DNA damage and DNA repair (e.g. spo11, rad21l1, nabp1b, spata22, tdrd9) were also affected in the soya bean fed group. Furthermore, our study suggests the plausible effect of yeast ß-glucan through the modulation of several genes that regulate immune responses and barrier integrity. Our findings indicate a subdued inflammation in juvenile zebrafish fed soya bean meal and the efficacy of ß-glucan to counter these subtle inflammatory responses.


Asunto(s)
Enfermedades de los Peces/prevención & control , Glycine max/química , Inflamación/veterinaria , Enfermedades Intestinales/prevención & control , Polisacáridos/metabolismo , Transcriptoma/efectos de los fármacos , Pez Cebra , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Suplementos Dietéticos/análisis , Enfermedades de los Peces/inmunología , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/inmunología , Inflamación/prevención & control , Enfermedades Intestinales/inmunología , Intestinos , Polisacáridos/administración & dosificación , Polisacáridos/química , Saccharomyces cerevisiae/química
5.
Pak J Pharm Sci ; 32(2): 617-624, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31081774

RESUMEN

In the present study, Pleurotus ostreatus IBL-02, a white rot basidiomycete was exploited for lipase production in solid-state fermentation (SSF). Different agro-industrial wastes such as canola-oilseed cake, cotton-oilseed cake, linseed-oil cake, sesame-oilseed cake, rice bran and wheat bran were screened for fermentative production of the lipolytic enzyme. The enzyme profile of P. ostreatus showed the highest activity of lipase on canola oil seed cake as a substrate under SSF conditions. Various physiological factors such as incubation time, humidity level, culture pH, incubation temperature and supplementation of carbon and nitrogen sources were optimized to induce the lipase synthesis capability of P. ostreatus at an optimal level. Optimum lipase activity (3256 U/gram dry substrate) was measured in the solid fermentation medium using moisture level, 50.0%; pH, 4.0; temperature, 30°C and olive oil, 2.0% after 72 h of incubation period with glucose and urea as carbon and nitrogen supplements, respectively. Glucose supplementation significantly stimulated the lipase production, while nitrogen addition did not exert any significant effect on lipase yield. Overall, under optimized bioprocess conditions, the enzyme activity was improved up to 1.6 folds with respect to the original enzyme activities. The current findings indicate that culture conditions have great influence on the lipase production potential of P. ostreatus for commercial purpose.


Asunto(s)
Medios de Cultivo/química , Lipasa/biosíntesis , Pleurotus/metabolismo , Biotecnología/métodos , Carbono/metabolismo , Fibras de la Dieta , Fermentación , Industria de Procesamiento de Alimentos , Concentración de Iones de Hidrógeno , Residuos Industriales , Nitrógeno/metabolismo , Aceite de Oliva , Temperatura , Factores de Tiempo
6.
Drug Chem Toxicol ; 39(3): 290-6, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26524343

RESUMEN

In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.


Asunto(s)
Antioxidantes/farmacología , Arsenitos/toxicidad , Daño del ADN , Contaminantes Ambientales/toxicidad , Quercetina/farmacología , Compuestos de Sodio/toxicidad , Espermatozoides/efectos de los fármacos , Administración Oral , Animales , Arsenitos/farmacocinética , Ensayo Cometa , Contaminantes Ambientales/farmacocinética , Epidídimo/efectos de los fármacos , Epidídimo/metabolismo , Epidídimo/patología , Masculino , Ratas Sprague-Dawley , Compuestos de Sodio/farmacocinética , Espectrofotometría Atómica , Recuento de Espermatozoides , Espermatozoides/patología , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología
7.
Contemp Oncol (Pozn) ; 20(2): 185-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27358600

RESUMEN

AIM OF THE STUDY: TRAIL-mediated signalling has emerged as an extensively studied biological mechanism reported to differentially induce apoptosis in cancer cells. However, overwhelmingly increasing experimentally verified data is shedding light on resistance against TRAIL-induced apoptosis in cancer cells. Moreover, genetic and epigenetic mutations also exert effects on the functionality of TRAIL and its receptors. In this study we investigated the association between breast cancer and polymorphisms in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in a Pakistani Population. MATERIAL AND METHODS: Genotyping for TRAIL gene 1595 C/T polymorphism was done for 363 breast cancer patients and 193 age- and sex-matched healthy controls. DNA was extracted using standard organic methods. PCR-RFLP analysis was done for C/T polymorphism at position 1595 in exon 5 of the TRAIL gene using site-specific primers and restriction enzyme. The results were statistically evaluated by SPSS14. RESULTS: In this study, CC homozygotes were 46.3% in patients and 49.7% in controls, p = 0.729 with OR value 0.8705 (95% CI: 0.6137-1.2348). CT was statistically insignificant, p = 0.837 with OR value 0.9242 (95% CI: 0.6494-1.3154). However, the minor allele or risk allele genotype TT had a higher percentage among breast cancer patients (12.1%) than in the control group (6.7%). Since there was a statistically insignificant difference (p = 0.212, OR value 1.9098 with 95% CI 1.0019 to 3.6406) of TT genotype between the two groups, the contrastingly higher percentage of TT genotype in breast cancer patients seems to be a risk factor for the disease. Moreover, the frequency of minor allele T was also found to be higher in the patients (0.329) than in the controls (0.285). CONCLUSIONS: The TRAIL gene 1595 C/T SNP has a contradictory role in cancer development in different populations. In our population group although the percentage of homozygous risk allele TT was higher in patients it was statistically non-significant. The raised T allele and TT genotype in patients may suggest its association with breast cancer in the Pakistani population.

8.
PLoS Pathog ; 8(2): e1002531, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22346756

RESUMEN

Gram-negative bacteria secrete virulence factors and assemble fibre structures on their cell surface using specialized secretion systems. Three of these, T2SS, T3SS and T4PS, are characterized by large outer membrane channels formed by proteins called secretins. Usually, a cognate lipoprotein pilot is essential for the assembly of the secretin in the outer membrane. The structures of the pilotins of the T3SS and T4PS have been described. However in the T2SS, the molecular mechanism of this process is poorly understood and its structural basis is unknown. Here we report the crystal structure of the pilotin of the T2SS that comprises an arrangement of four α-helices profoundly different from previously solved pilotins from the T3SS and T4P and known four α-helix bundles. The architecture can be described as the insertion of one α-helical hairpin into a second open α-helical hairpin with bent final helix. NMR, CD and fluorescence spectroscopy show that the pilotin binds tightly to 18 residues close to the C-terminus of the secretin. These residues, unstructured before binding to the pilotin, become helical on binding. Data collected from crystals of the complex suggests how the secretin peptide binds to the pilotin and further experiments confirm the importance of these C-terminal residues in vivo.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa/metabolismo , Sistemas de Secreción Bacterianos/fisiología , Enterobacteriaceae/metabolismo , Secretina/metabolismo , Secuencia de Aminoácidos , Proteínas de la Membrana Bacteriana Externa/química , Cristalización , Enterobacteriaceae/química , Enterobacteriaceae/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Unión Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Secretina/química , Análisis de Secuencia de ADN
9.
Chemosphere ; 362: 142747, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38960051

RESUMEN

The widespread occurence of pharmaceutical pollutants seriously threatens the environment and human well-being. In the present study, zinc ferrite nanoparticles (ZnFe2O4 NPs) have been synthesized by co-precipitation method and used as photocatalyst for the degradation of two most commonly prescribed painkillers, piroxicam (PXM) and paracetamol (PCM), via heterogeneous Fenton process under the solar light. The synthesized ZnFe2O4 NPs showed a narrower band gap i.e. 1.87 eV, signifying the ability to efficiently work in visible light range. In context of photocatalytic applications, the operational conditions were optimized to achieve maximum degradation. PCM and PXM were completely degraded (100%) at the optimized photocatalytic dose (20 mg L-1), reaction time (180 min), initial drug concentration (10 mg L-1), and pH (6.0), which is close to the natural environment. The extent of mineralization as estimated by the reduction of total organic carbon (TOC) was observed to be ∼91 and 82% for PCM and PXM respectively. Kinetic studies revealed that photocatalytic degradation followed pseudo-first-order kinetics. Moreover, the ZnFe2O4 NPs retained ∼90 % of photocatalytic activity after five consecutive reaction cycles, showing remarkable reusability and stability of catalyst.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38867525

RESUMEN

BACKGROUND: Oleogelation is an efficient and emerging approach for obtaining biocompatible and biodegradable elastic semisolid crystals to be used in various cosmetic and pharmaceutical formulations. Recently, drug incorporation in oil structuring has been a promising strategy under consideration due to the effectiveness of this method. Plant oils have very beneficial characteristics for skin care and wound healing due to the presence of certain antioxidants. METHODS: In this study, the oleogels of Moringa oleifera seed oil with natural polysaccharides, including pectin, chitosan, and xanthan gum, were prepared using the emulsion template method. Moringa oil was selected because it can hydrate and moisturize the skin and has great antioxidant activity. Also, the natural polysaccharides, i.e., pectin and chitosan, exhibited good gelling properties. Allantoin, which is a wound healer and eucalyptus leaf oil with antioxidant potential, was incorporated into the emulsion-based-oleogels to enhance the antioxidant and antimicrobial activity of the oleogels. RESULTS: Allantoin and eucalyptus-loaded oleogels exhibited good antibacterial activity against E. coli. The FTIR spectra of moringa-based oleogels in the range between 3226-3422 cm-1 indicate the presence of hydrogen bonding in oleogels. CONCLUSION: The antioxidant potential of allantoin and eucalyptus-containing oleogel was maximized, and an IC50 value of 0.9719 µM was found. Maximum release of allantoin from oleogel was observed in the first hour.

11.
Environ Pollut ; 348: 123835, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38521395

RESUMEN

Plastic pollution, including micro- and nanoplastics, is a growing concern. Tyre-wear particles (TWPs) are the second largest source of microplastics in the ocean following abrasion of synthetic fibres. In addition to the particles themselves, TWPs contain many harmful chemicals, including 6PPD. This chemical reacts with atmospheric ozone and forms the toxic compound 6PPD-quinone (6PPDq), which poses a danger to aquatic life. There is a knowledge gap in understanding risks associated with the combined toxicity of nanoplastics (NPs) and 6PPDq. The present study aimed to investigate the toxicity of NPs and 6PPDq on adult zebrafish using phenotypic (behaviour, histology) and transcriptomic endpoints. Zebrafish were exposed to four treatments: control (contaminant-free), 50 µg/L 6PPDq, 3 mg/L polystyrene (PS)-NPs, and a combination of 50 µg/L 6PPDq and 3 mg/L PS-NPs. We did not observe locomotory dysregulation in zebrafish exposed to NPs. However, we found significant hyperlocomotion in zebrafish exposed to 6PPDq and this effect was even more substantial after co-exposure with PS-NPs. This study explores the molecular mechanisms behind these effects, identifying genes associated with neurotransmitters and fatty acid metabolism that were dysregulated by the co-exposure. Transcriptomic analysis further showed that both 6PPDq and PS-NPs impacted cellular processes associated with sterol biosynthesis, cholesterol metabolism, and muscle tissue development. The effects on these mechanisms were stronger in co-exposed zebrafish, indicating a heightened risk to cellular integrity and mitochondrial dysfunction. These results highlight the significance of mixture toxicity when studying the effects of NPs and associated chemicals like 6PPDq.


Asunto(s)
Benzoquinonas , Nanopartículas , Contaminantes Químicos del Agua , Animales , Pez Cebra , Microplásticos/toxicidad , Poliestirenos/toxicidad , Plásticos/toxicidad , Quinonas , Contaminantes Químicos del Agua/toxicidad
12.
Nat Commun ; 15(1): 4912, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851738

RESUMEN

Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires' disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations. Here we report the crystal structure of the Lcl C-terminal domain (Lcl-CTD) and present a model for intact Lcl. Our data reveal that Lcl-CTD forms an unusual trimer arrangement with a positively charged external surface and negatively charged solvent exposed internal cavity. Through molecular dynamics simulations, we show how the glycosaminoglycan chondroitin-4-sulphate associates with the Lcl-CTD surface via distinct binding modes. Our findings show that Lcl homologs are present across both the Pseudomonadota and Fibrobacterota-Chlorobiota-Bacteroidota phyla and suggest that Lcl may represent a versatile carbohydrate-binding mechanism.


Asunto(s)
Proteínas Bacterianas , Colágeno , Glicosaminoglicanos , Legionella pneumophila , Simulación de Dinámica Molecular , Unión Proteica , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Legionella pneumophila/metabolismo , Colágeno/metabolismo , Colágeno/química , Cristalografía por Rayos X , Sulfatos de Condroitina/metabolismo , Sulfatos de Condroitina/química , Adhesión Bacteriana , Dominios Proteicos , Enfermedad de los Legionarios/microbiología , Enfermedad de los Legionarios/metabolismo , Humanos , Secuencia de Aminoácidos
13.
Acta Crystallogr D Biol Crystallogr ; 69(Pt 8): 1381-6, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23897461

RESUMEN

The secretins are a family of large multimeric channels in the outer membrane of Gram-negative bacteria that are involved in protein export. In Dickeya dadantii and many other pathogenic bacteria, the lipoprotein pilotin targets the secretin subunits to the outer membrane, allowing a functional type II secretion system to be assembled. Here, the crystal structure of the C-terminal peptide of the secretin subunit bound to its cognate pilotin is reported. In solution, this C-terminal region of the secretin is nonstructured. The secretin peptide folds on binding to the pilotin to form just under four turns of α-helix which bind tightly up against the first helix of the pilotin so that the hydrophobic residues of the secretin helix can bind to the hydrophobic surface of the pilotin. The secretin helix binds parallel to the first part of the fourth helix of the pilotin. An N-capping aspartate encourages helix formation and binding by interacting favourably with the helix dipole of the helical secretin peptide. The structure of the secretin-pilotin complex of the phytopathogenic D. dadantii described here is a paradigm for this interaction in the OutS-PulS family of pilotins, which is essential for the correct assembly of the type II secretion system of several potent human adversaries, including enterohaemorrhagic Escherichia coli and Klebsiella oxytoca.


Asunto(s)
Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Enterobacteriaceae/metabolismo , Proteínas Ligadas a Lípidos/química , Proteínas Ligadas a Lípidos/metabolismo , Secretina/química , Secretina/metabolismo , Secuencia de Aminoácidos , Sistemas de Secreción Bacterianos/fisiología , Sitios de Unión , Secuencia Conservada , Cristalografía por Rayos X , Enterobacteriaceae/patogenicidad , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Datos de Secuencia Molecular , Péptidos/química , Péptidos/metabolismo , Unión Proteica , Conformación Proteica , Pliegue de Proteína
14.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1868(11): 159383, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37657755

RESUMEN

Dyslipidemia is often associated with unhealthy dietary habits, and many mammalian studies have explored the mode of action of certain bioactive compounds such as ß-glucans and n-3 PUFAs to understand their potential to normalize the lipid metabolism. There are only a few investigations that adopted omic approaches to unveil their combined effect on hypercholesterolemia. Zebrafish (Danio rerio) was used as a model organism to reveal the efficacy of Schizochytrium oil and ß-glucans (from Euglena gracilis and Phaeodactylum tricornutum) against cholesterol-rich diet induced dyslipidemia. One of the folowing four diets was fed to a particular group of fish: a control high-cholesterol diet, a Schizochytrium oil diet or one of the two diets containing the oil and ß-glucan. The plasma HDL, expression of hepatic genes linked to, among others, ferric ion binding and plasma phosphatidylcholines were higher and plasma cholesterol esters and triacylglycerols were lower in the microbial oil-fed fish compared to the fish fed high cholesterol diet. While the fish fed a mix of microbial oil and Euglena ß-glucan had lower plasma triacylglycerols and expression of hepatic genes linked to PPAR signaling pathway and enriched biosynthesis of plasma unsaturated fatty acids, the fish fed microbial oil-Phaeodactylum ß-glucan combination had lower abundance of triacylglycerols rich in saturated and mono-unsaturated fatty acids and cholesterol esters in the plasma.

15.
Front Nutr ; 10: 1161119, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37435570

RESUMEN

A Western diet elevates the circulating lipoprotein and triglyceride levels which are the major risk factors in cardiovascular disease (CVD) development. Consumption of long-chain omega-3 fatty acids can stall the disease progression. Although these fatty acids can significantly impact the intestine under a hypercholesterolemic condition, the associated changes have not been studied in detail. Therefore, we investigated the alterations in the intestinal transcriptome along with the deviations in the plasma lipids and liver histomorphology of zebrafish offered DHA- and EPA-rich oil. Fish were allocated to 4 dietary treatments: a control group, a high cholesterol group and microbial oil groups with low (3.3%) and high (6.6%) inclusion levels. We quantified the total cholesterol, lipoprotein and triglyceride levels in the plasma. In addition, we assessed the liver histology, intestinal transcriptome and plasma lipidomic profiles of the study groups. The results suggested that higher levels of dietary microbial oil could control the CVD risk factor indices in zebrafish plasma. Furthermore, microbial oil-fed fish had fewer liver vacuoles and higher mRNA levels of genes involved in ß-oxidation and HDL maturation. Analyses of the intestine transcriptome revealed that microbial oil supplementation could influence the expression of genes altered by a hypercholesterolemic diet. The plasma lipidomic profiles revealed that the higher level of microbial oil tested could elevate the long-chain poly-unsaturated fatty acid content of triglyceride species and lower the concentration of several lysophosphatidylcholine and diacylglycerol molecules. Our study provides insights into the effectiveness of microbial oil against dyslipidemia in zebrafish.

16.
Front Immunol ; 14: 1183701, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37275890

RESUMEN

Alginate oligosaccharides (AOS) are natural bioactive compounds with anti-inflammatory properties. We performed a feeding trial employing a zebrafish (Danio rerio) model of soybean-induced intestinal inflammation. Five groups of fish were fed different diets: a control (CT) diet, a soybean meal (SBM) diet, a soybean meal+ß-glucan (BG) diet and 2 soybean meal+AOS diets (alginate products differing in the content of low molecular weight fractions - AL, with 31% < 3kDa and AH, with 3% < 3kDa). We analyzed the intestinal transcriptomic and plasma metabolomic profiles of the study groups. In addition, we assessed the expression of inflammatory marker genes and histological alterations in the intestine. Dietary algal ß-(1, 3)-glucan and AOS were able to bring the expression of certain inflammatory genes altered by dietary SBM to a level similar to that in the control group. Intestinal transcriptomic analysis indicated that dietary SBM changed the expression of genes linked to inflammation, endoplasmic reticulum, reproduction and cell motility. The AL diet suppressed the expression of genes related to complement activation, inflammatory and humoral response, which can likely have an inflammation alleviation effect. On the other hand, the AH diet reduced the expression of genes, causing an enrichment of negative regulation of immune system process. The BG diet suppressed several immune genes linked to the endopeptidase activity and proteolysis. The plasma metabolomic profile further revealed that dietary SBM can alter inflammation-linked metabolites such as itaconic acid, taurochenodeoxycholic acid and enriched the arginine biosynthesis pathway. The diet AL helped in elevating one of the short chain fatty acids, namely 2-hydroxybutyric acid while the BG diet increased the abundance of a vitamin, pantothenic acid. Histological evaluation revealed the advantage of the AL diet: it increased the goblet cell number and length of villi of the intestinal mucosa. Overall, our results indicate that dietary AOS with an appropriate amount of < 3kDa can stall the inflammatory responses in zebrafish.


Asunto(s)
Pez Cebra , beta-Glucanos , Animales , Pez Cebra/metabolismo , beta-Glucanos/farmacología , beta-Glucanos/metabolismo , Intestinos , Inflamación , Glycine max , Oligosacáridos/farmacología , Oligosacáridos/metabolismo
17.
bioRxiv ; 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38106198

RESUMEN

Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires' disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans (GAGs) on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations. Here we report the crystal structure of the Lcl C-terminal domain (Lcl-CTD) and present a model for intact Lcl. Our data reveal that Lcl-CTD forms an unusual dynamic trimer arrangement with a positively charged external surface and a negatively charged solvent exposed internal cavity. Through Molecular Dynamics (MD) simulations, we show how the GAG chondroitin-4-sulphate associates with the Lcl-CTD surface via unique binding modes. Our findings show that Lcl homologs are present across both the Pseudomonadota and Fibrobacterota-Chlorobiota-Bacteroidota phyla and suggest that Lcl may represent a versatile carbohydrate binding mechanism.

18.
ScientificWorldJournal ; 2012: 179782, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22545008

RESUMEN

The Ocean, which is called the "mother of origin of life," is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria.


Asunto(s)
Cianobacterias/metabolismo , Descubrimiento de Drogas , Biología Marina , Antineoplásicos , Antivirales , Inhibidores Enzimáticos , Protectores contra Radiación
19.
Front Immunol ; 13: 1018768, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36389790

RESUMEN

Soybean meal evokes diet-induced intestinal inflammation in certain fishes. Although the molecular aspects of soybean-induced intestinal inflammation in zebrafish are known, the impact of the inflammatory diet on fish behavior remain largely underexplored. We fed zebrafish larvae with three diets - control, soybean meal and soybean meal with ß-glucan to gain deeper insight into the behavioral changes associated with the soybean meal-induced inflammation model. We assessed the effect of the diets on the locomotor behavior, morphological development, oxygen consumption and larval transcriptome. Our study revealed that dietary soybean meal can reduce the locomotor activity, induce developmental defects and increase the oxygen demand in zebrafish larvae. Transcriptomic analysis pointed to the suppression of genes linked to visual perception, organ development, phototransduction pathway and activation of genes linked to the steroid biosynthesis pathway. On the contrary, ß-glucan, an anti-inflammatory feed additive, counteracted the behavioral and phenotypic changes linked to dietary soybean. Although we did not identify any differentially expressed genes from the soybean meal alone fed group vs soybean meal + ß-glucan-fed group comparison, the unique genes from the comparisons of the two groups with the control likely indicate reduction in inflammatory cytokine signaling, inhibition of proteolysis and induction of epigenetic modifications by the dietary glucan. Furthermore, we found that feeding an inflammatory diet at the larval stage can lead to long-lasting developmental defects. In conclusion, our study reveals the extra-intestinal manifestations associated with soybean meal-induced inflammation model.


Asunto(s)
Pez Cebra , beta-Glucanos , Animales , Alimentación Animal/análisis , Dieta/efectos adversos , Inflamación/genética , Glycine max , Larva
20.
Int J Biol Macromol ; 220: 683-691, 2022 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-35987366

RESUMEN

An extracellular pectinase from a mixed consortium of Bacillus sp. (BSP) was immobilized onto graphene oxide/chitosan composite (GO/CS) through covalent binding to enhance its recycling and operational stability features. Different parameters were optimized, including cross-linker concentration (%), time, pH, and GO/CS-pectinase ratios. GO/CS-pectinase was further characterized by FT-IR and XRD. The activity of GO/CS-pectinase was reached up to 804 µmolmin-1 with an immobilization efficiency of 80.64 ± 1.15 % under optimum conditions. GO/CS-pectinase exhibited a 3.0-folds higher half-life (t1/2) than free pectinase at 50, 55, and 60 °C, respectively. The Vmax and KM values of GO/CS-pectinase were found to be nearly equal to the free pectinase indicating that conformational flexibility was retained. Kd, t1/2, ∆G*, ∆H*, and ∆S* of both free pectinase and GO/CS-pectinase was 0.0339 & 0.0721 min-1, 9.62 and 40.44 min, 81.35, 90.72 kJmol-1, 47.098 & 63.635 kJmol-1, -102.86 & -81.340 Jmole-1 K-1. SEM morphological analysis further confirmed the successful binding of pectinase with GO/CS, which retained about 92 % of its original catalytic activity after ten consecutive reaction cycles. Finally, GO/CS-pectinase was employed for guava juice clarification which exhibited the turbidity reduction up to 81 % after 75 min of treatment.


Asunto(s)
Quitosano , Grafito , Quitosano/química , Enzimas Inmovilizadas/química , Grafito/química , Concentración de Iones de Hidrógeno , Poligalacturonasa/química , Espectroscopía Infrarroja por Transformada de Fourier
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