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1دورية أكاديمية
المؤلفون: Díaz, Roberto Efraín, Ecker, Andrew K, Correy, Galen J, Asthana, Pooja, Young, Iris D, Faust, Bryan, Thompson, Michael C, Seiple, Ian B, Van Dyken, Steven, Locksley, Richard M, Fraser, James S
مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Underpinning research, 1.1 Normal biological development and functioning, Chitinases, Animals, Hydrogen-Ion Concentration, Mice, Molecular Dynamics Simulation, Chitin, Protein Conformation, Crystallography, X-Ray, Protein Binding, Ligands, Kinetics, Acetylglucosamine, Models, Molecular, enzyme, chitin, lung, E. coli, Human, Mouse, biochemistry, chemical biology, human, molecular biophysics, mouse, structural biology, Biological sciences, Biomedical and clinical sciences, Health sciences
الوصف: Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across a broad pH range, quantifying its unusual dual activity optima at pH 2 and 7. We also solved high-resolution crystal structures of mAMCase in complex with oligomeric GlcNAcn, the building block of chitin, where we identified extensive conformational ligand heterogeneity. Leveraging these data, we conducted molecular dynamics simulations that suggest how a key catalytic residue could be protonated via distinct mechanisms in each of the two environmental pH ranges. These results integrate structural, biochemical, and computational approaches to deliver a more complete understanding of the catalytic mechanism governing mAMCase activity at different pH. Engineering proteins with tunable pH optima may provide new opportunities to develop improved enzyme variants, including AMCase, for therapeutic purposes in chitin degradation.
وصف الملف: application/pdf
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2دورية أكاديمية
المؤلفون: Kim, Do-Hyun, Wang, Yilin, Jung, Haerin, Field, Rachael, Zhang, Xinya, Liu, Ta-Chiang, Ma, Changqing, Brestoff, Jonathan, Van Dyken, Steven, Fraser, James
المصدر: Science. 381(6662)
مصطلحات موضوعية: Animals, Mice, Chitin, Immunity, Innate, Lymphocytes, Obesity, Stomach, Adaptation, Physiological, Dietary Fiber, Chitinases, Digestion
الوصف: Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/0hd6j43cTest
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3دورية أكاديمية
المؤلفون: Guessous, Ghita, Patsalo, Vadim, Balakrishnan, Rohan, Çağlar, Tolga, Williamson, James R, Hwa, Terence
المصدر: Nature Microbiology. 8(9)
مصطلحات موضوعية: Microbiology, Biological Sciences, Life Below Water, Chitin, Chitinases, Vibrio, Medical Microbiology
الوصف: Many biogeochemical functions involve bacteria utilizing solid substrates. However, little is known about the coordination of bacterial growth with the kinetics of attachment to and detachment from such substrates. In this quantitative study of Vibrio sp. 1A01 growing on chitin particles, we reveal the heterogeneous nature of the exponentially growing culture comprising two co-existing subpopulations: a minority replicating on chitin particles and a non-replicating majority which was planktonic. This partition resulted from a high rate of cell detachment from particles. Despite high detachment, sustained exponential growth of cells on particles was enabled by the enrichment of extracellular chitinases excreted and left behind by detached cells. The 'inheritance' of these chitinases sustains the colonizing subpopulation despite its reduced density. This simple mechanism helps to circumvent a trade-off between growth and dispersal, allowing particle-associated marine heterotrophs to explore new habitats without compromising their fitness on the habitat they have already colonized.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/59v14774Test
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4دورية أكاديمية
المؤلفون: Kim, Andrea D, Kui, Lin, Kaufmann, Benedikt, Kim, Sung Eun, Leszczynska, Aleksandra, Feldstein, Ariel E
المصدر: Journal of Molecular Medicine. 101(7)
مصطلحات موضوعية: Nutrition, Liver Disease, Digestive Diseases, Hepatitis, Chronic Liver Disease and Cirrhosis, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Oral and gastrointestinal, Mice, Humans, Animals, Non-alcoholic Fatty Liver Disease, Chitinases, Interleukin-13 Receptor alpha2 Subunit, Liver, Liver Cirrhosis, Diet, High-Fat, Mice, Knockout, Mice, Inbred C57BL, Disease Models, Animal, Chitinase-like proteins, Non-alcoholic fatty liver disease, Hepatic stellate cells, Infiltrating macrophages, Medicinal and Biomolecular Chemistry, Immunology
الوصف: Chitinase-3-like 1 protein (CHI3L1) is a secreted glycoprotein, strongly correlated with fibrosis severity in chronic liver diseases including non-alcoholic steatohepatitis (NASH). However, the mechanisms by which CHI3L1 contributes to fibrogenesis remain undefined. Here, we showed that infiltrating monocyte-derived liver macrophages represent the main source of CHI3L1 in murine NASH. We developed a floxed CHI3L1 knock-out (KO) mouse to further study the cell-specific role of CHI3L1 ablation. Wildtype (WT) and myeloid cell-specific CHI3L1 KO mice (CreLyz) were challenged with a highly inflammatory and fibrotic dietary model of NASH by administering choline-deficient high-fat diet for 10 weeks. Macrophage accumulation and inflammatory cell recruitment were significantly ameliorated in the CreLyz group compared to WT (F4/80 IHC p
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/76f4374gTest
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5دورية أكاديمية
المؤلفون: Ruiling Zhang, Wenjuan Liu, Jingwen Fu, Zhong Zhang
المصدر: Parasites & Vectors, Vol 16, Iss 1, Pp 1-12 (2023)
مصطلحات موضوعية: miRNA, Chitin metabolism, Mosquito, Chitin synthases, Chitinases, Infectious and parasitic diseases, RC109-216
الوصف: Abstract Background Aedes albopictus is a vector of numerous devastating arboviruses and places heavy burdens on global public health. Chitin is one of the important components of cuticles and targeting chitin metabolism is a promising strategy for preventing mosquito dispersal and mosquito-borne diseases. Increasing evidence suggests that microRNAs (miRNAs) play crucial roles in various physiological processes of insects. Methods A previous analysis suggested that the microRNA miR-989 is potentially involved in chitin metabolism in Ae. albopictus pupae. In the present study, we found that the expression level of miR-989 was significantly overexpressed after injection of agomir. A dual-luciferase assay was used to determine the direct target of miR-989. Survival rate, eclosion rate and malformation rate were statistically analyzed to evaluate the potential effect of miR-989. Hematoxylin–eosin staining and chitin staining were used to evaluate the microstructural changes in the cuticles of Ae. albopictus pupae. Results Overexpression of miR-989 resulted in a significantly reduced survival rate and eclosion rate of pupae and an elevated malformation rate of adults. The results suggested that miR-989 acted as a regulator of chitin metabolism in Ae. albopictus pupae by affecting the transcript levels of the Ae. albopictus genes encoding chitin synthase 1 (AaCHS1) and chitinase 10 (AaCht10). The altered expression levels of the two chitin metabolism-related enzymes (CHS1 and Cht10, respectively) caused the structural changes in cuticles and further affected the pupal-adult transition process of Ae. albopictus. XM_029863591.1 was proven to be the target gene of miR-989 and displayed similar effects on pupae as miR-989. Conclusions The microRNA miR-989 was found to be essential for chitin metabolism in old and new cuticles of Ae. albopictus pupae. The results of the current study suggested that miR-989 could be used as a potential target to control Ae. albopictus. Graphical Abstract
وصف الملف: electronic resource
العلاقة: https://doaj.org/toc/1756-3305Test
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6دورية أكاديمية
المؤلفون: Abdul Ghani, Syed Ali Imran Bokhari, Syed Anees Ali, Muhammad Faheem, Suliman Yousef Alomar, Muhammad Mudassir Basheir, Naushad Ahmad, Sana Irshad
المصدر: Journal of King Saud University: Science, Vol 36, Iss 1, Pp 103036- (2024)
مصطلحات موضوعية: Microbial Chitinases, Nanoparticles, Plant protection, Nanobiofungicide, Science (General), Q1-390
الوصف: Objectives: In the current study, a new potential nanobiofungicide was investigated as hybrid composite antifungals; zinc oxide nanoparticles (ZNPs) in combination with microbial hydrolytic enzymes (Chitinases). Methods: The Chitinase enzyme was achieved from a local isolate, which was identified as Bacillus licheniformis AG-W3. The enzyme production was achieved after 72 h of incubation at pH 7.5 and temperature 45 °C. The mean diameter of the synthesized nanoparticles (38–76 nm) was established by means of scanning electron microscope (SEM). Additionally, their antifungal activity was evaluated against Fusarium species. Results: Based on the results obtained, ZNPs amended with Chitinase at 0.1 % concentrations showed the strongest inhibitory effect (89.1 %). A synergistic effect of Chitinase (0.03U/ml) in combination with ZNPs (0.005 %) was observed up to 89.1 %. The SEM results exhibits agglomerated spherical particles due to high surface energy. The average size calculated for calcined zinc nanoparticles are (38–76 nm) and this is in good agreement with the XRD results (Eq. (1): 46 nm). Conclusions: It was concluded that the combination of ZNPs with Chitinase enzyme exhibits enhanced antifungal activity compared to their individual effects, considered a new alternative for synthetic fungicides. The development of novel nanocomposites for sustainable management of fungal diseases can mitigate the emergence of persistent and resilient fungal diseases and the crop losses that they cause. In addition, the importance of the current study was to establishing a consortium of chitinolytic microorganisms and nanoparticles appears to bring superior outcomes in fighting fungal phytopathogens, and also a potential alternative to these chemical pesticides, residing in soil and already the part of endophytic microbiome, have minimum altering effect on ecosystem.
وصف الملف: electronic resource
العلاقة: http://www.sciencedirect.com/science/article/pii/S1018364723004986Test; https://doaj.org/toc/1018-3647Test
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7دورية أكاديمية
المؤلفون: Ebtehag A.E. Sakr
مصطلحات موضوعية: Chitin Metabolism in Insects and Mammals, Molecular Biology, Biochemistry, Genetics and Molecular Biology, Life Sciences, Microbial Enzymes and Biotechnological Applications, Biotechnology, Technologies for Biofuel Production from Biomass, Biomedical Engineering, FOS Medical engineering, Engineering, Physical Sciences, Chitinases, Chitinase, Chitin, Bioremediation, Response surface methodology, Food science, Biochemistry, Chemistry, Biology, Microbiology, FOS Biological sciences, Bacteria, Enzyme, Chromatography, Chitosan, Genetics
الوصف: Background Hydrocarbon pollution stemming from petrochemical activities is a significant global environmental concern. Bioremediation, employing microbial chitinase-based bioproducts to detoxify or remove contaminants, presents an intriguing solution for addressing hydrocarbon pollution. Chitooligosaccharides, a product of chitin degradation by chitinase enzymes, emerge as key components in this process. Utilizing chitinaceous wastes as a cost-effective substrate, microbial chitinase can be harnessed to produce Chitooligosaccharides. This investigation explores two strategies to enhance chitinase productivity, firstly, statistical optimization by the Plackett Burman design approach to evaluating the influence of individual physical and chemical parameters on chitinase production, Followed by response surface methodology (RSM) which delvs into the interactions among these factors to optimize chitinase production. Second, to further boost chitinase production, we employed heterologous expression of ... : يشكل التلوث الهيدروكربوني الناجم عن أنشطة البتروكيماويات مصدر قلق بيئي عالمي كبير. تقدم المعالجة الحيوية، باستخدام المنتجات الحيوية القائمة على الكيتيناز الميكروبي لإزالة السموم أو الملوثات، حلاً مثيرًا للاهتمام لمعالجة التلوث الهيدروكربوني. تظهر السكريات الشيتولية، وهي نتاج تحلل الكيتين بواسطة إنزيمات الكيتيناز، كمكونات رئيسية في هذه العملية. باستخدام نفايات الكيتينا كركيزة فعالة من حيث التكلفة، يمكن تسخير الكيتيناز الميكروبي لإنتاج السكريات الشيتولية. يستكشف هذا التحقيق استراتيجيتين لتعزيز إنتاجية الكيتيناز، أولاً، التحسين الإحصائي من خلال نهج تصميم Plackett Burman لتقييم تأثير المعلمات الفيزيائية والكيميائية الفردية على إنتاج الكيتيناز، تليها منهجية سطح الاستجابة (RSM) التي تتعمق في التفاعلات بين هذه العوامل لتحسين إنتاج الكيتيناز. ثانيًا، لتعزيز إنتاج الكيتيناز، استخدمنا تعبيرًا غير متجانس عن جين تشفير الكيتيناز في E. coli BL21(DE3) باستخدام ناقل مناسب. إن تعزيز نشاط الكيتيناز لا يعزز الإنتاجية فحسب، بل يزيد أيضًا من إنتاج السكريات الشيتولية، والتي تم العثور عليها لاستخدامها كمستحلبات. النتائج في هذه ...
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8دورية أكاديمية
المؤلفون: Gavala, M L, Kelly, E A B, Esnault, Stéphane, Kukreja, S, Evans, M D, Bertics, P J, Chupp, G L, Jarjour, N N
المساهمون: Université de Lille, Inserm, CHU Lille
مصطلحات موضوعية: Adipokines, Adult, Airway Remodeling, Allergens, Asthma, Bronchial Provocation Tests, Bronchoalveolar Lavage Fluid, Chemokines, CC, Chitinase-3-Like Protein 1, Chitinases, Cytokines, Enzyme Activation, Female, Humans, Inflammation Mediators, Lectins, Male, Time Factors, Young Adult
الوصف: Allergic airway inflammation contributes to the airway remodelling that has been linked to increased obstruction and morbidity in asthma. However, the mechanisms by which allergens contribute to airway remodelling in humans are not fully established. CCL18, chitotriosidase (CHIT1) and YKL-40 are readily detectable in the lungs and contribute to remodelling in other fibrotic diseases, but their involvement in allergic asthma is unclear. We hypothesized that CCL18, YKL-40 and CHIT1 bioactivity are enhanced in allergic asthma subjects after segmental allergen challenge and are related to increased pro-fibrotic and Th2-associated mediators in the lungs. Levels of CCL18 and YKL-40 protein and chitotriosidase (CHIT1) bioactivity in bronchoalveolar lavage (BAL) fluid, as well as CCL18, YKL-40 and CHIT1 mRNA levels in BAL cells were evaluated in patients with asthma at baseline and 48 h after segmental allergen challenge. We also examined the correlation between CCL18 and YKL-40 levels and CHIT1 activity with the levels of other pro-fibrotic factors and chemokines previously shown to be up-regulated after allergen challenge. Chitotriosidase activity and YKL-40 and CCL18 levels were elevated after segmental allergen challenge and these levels correlated with those of other pro-fibrotic factors, T cell chemokines, and inflammatory cells after allergen challenge. CCL18 and YKL-40 mRNA levels also increased in BAL cells after allergen challenge. Our results suggest that CCL18 and YKL-40 levels and CHIT1 activity are enhanced in allergic airway inflammation and thus may contribute to airway remodelling in asthma. ; 43
وصف الملف: application/octet-stream
العلاقة: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology; Clin Exp Allergy; http://hdl.handle.net/20.500.12210/89546Test
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9دورية أكاديمية
المؤلفون: Kodosaki, E, Watkins, WJ, Loveless, S, Kreft, KL, Richards, A, Anderson, V, Hurler, L, Robertson, NP, Zelek, WM, Tallantyre, EC
المصدر: Journal of Neuroinflammation , 21 , Article 52. (2024)
مصطلحات موضوعية: Biomarkers, Cerebrospinal fluid, Complement, Multiple sclerosis, Prediction, Serum, Humans, Osteopontin, Vitamin D-Binding Protein, Chitinases, Recurrence
الوصف: Establishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination of biomarkers would increase the accuracy of prediction models to differentiate multiple sclerosis from other neurological disorders and enhance prognostication for people with multiple sclerosis. We measured 24 fluid biomarkers in the blood and cerebrospinal fluid of 77 people with multiple sclerosis and 80 people with other neurological disorders, using ELISA or Single Molecule Array assays. Primary outcomes were multiple sclerosis versus any other diagnosis, time to first relapse, and time to disability milestone (Expanded Disability Status Scale 6), adjusted for age and sex. Multivariate prediction models were calculated using the area under the curve value for diagnostic prediction, and concordance statistics (the percentage of each pair of events that are correctly ordered in time for each of the Cox regression models) for prognostic predictions. Predictions using combinations of biomarkers were considerably better than single biomarker predictions. The combination of cerebrospinal fluid [chitinase-3-like-1 + TNF-receptor-1 + CD27] and serum [osteopontin + MCP-1] had an area under the curve of 0.97 for diagnosis of multiple sclerosis, compared to the best discriminative single marker in blood (osteopontin: area under the curve 0.84) and in cerebrospinal fluid (chitinase-3-like-1 area under the curve 0.84). Prediction for time to next relapse was optimal with a combination of cerebrospinal fluid[vitamin D binding protein + Factor I + C1inhibitor] + serum[Factor B + Interleukin-4 + C1inhibitor] (concordance 0.80), and time to Expanded Disability Status Scale 6 with cerebrospinal fluid [C9 + Neurofilament-light] + serum[chitinase-3-like-1 + CCL27 + vitamin D binding protein + C1inhibitor] (concordance 0.98). A combination of fluid biomarkers has a higher accuracy to differentiate multiple sclerosis from other neurological disorders and ...
وصف الملف: application/pdf
العلاقة: https://discovery.ucl.ac.uk/id/eprint/10188303/1/s12974-024-03036-4.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10188303Test/
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10دورية أكاديمية
المؤلفون: Blazevic, Nina, Rogic, Dunja, Pelajic, Stipe, Miler, Marijana, Glavcic, Goran, Ratkajec, Valentina, Vrkljan, Nikolina, Bakula, Dejan, Hrabar, Davor, Pavic, Tajana
المصدر: Biochemia Medica ; ISSN 1330-0962 (Print) ; ISSN 1846-7482 (Online) ; Volume 34 ; Issue 1 (online first)
مصطلحات موضوعية: chitinases, Chitinase-3-Like Protein 1, biomarkers, YKL-40, inflammation
الوصف: Highlights YKL-40 is a biomarker for inflammatory diseases’ diagnosis and prediction YKL-40 concentration increases with age and has variations in healthy population YKL-40 is convincing in pancreatic/liver disease, arthritis, bronchitis, and sepsis YKL-40 is debatable in cardiovascular/neurological/renal disease, diabetes, asthma Future larger studies and age-stratified reference intervals of YKL-40 are needed YKL-40 or Chitinase-3-Like Protein 1 (CHI3L1) is a highly conserved glycoprotein that binds heparin and chitin in a non-enzymatic manner. It is a member of the chitinase protein family 18, subfamily A, and unlike true chitinases, YKL-40 is a chitinase-like protein without enzymatic activity for chitin. Although its accurate function is yet unknown, the pattern of its expression in the normal and disease states suggests its possible engagement in apoptosis, inflammation and remodeling or degradation of the extracellular matrix. During an inflammatory response, YKL-40 is involved in a complicated interaction between host and bacteria, both promoting and attenuating immune response and potentially being served as an autoantigen in a vicious circle of autoimmunity. Based on its pathophysiology and mechanism of action, the aim of this review was to summarize research on the growing role of YKL-40 as a persuasive biomarker for inflammatory diseases’ early diagnosis, prediction and follow-up (e.g., cardiovascular, gastrointestinal, endocrinological, immunological, musculoskeletal, neurological, respiratory, urinary, infectious) with detailed structural and functional background of YKL-40.
وصف الملف: application/pdf
العلاقة: https://hrcak.srce.hr/312200Test
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