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1دورية أكاديمية
المؤلفون: Kai Zhang, Lina Zhang, Mengyu Han, Zhiping Pu, Jinjing Zhong, Yanmei Hou, Peng Zhou
مصطلحات موضوعية: Biophysics, Biochemistry, Medicine, Microbiology, Cell Biology, Immunology, Developmental Biology, Cancer, Mental Health, Hematology, Biological Sciences not elsewhere classified, mouse model due, mast cell degranulation, epithelial barrier integrity, cholera toxin adjuvant, 2h3 cell model, common food allergy, milk protein α, study found differences, activation cow ’, goat milk α, higher potential sensitization, milk allergy, goat α, study aimed, investigate differences, higher production, cow α, th2 responses, th2 cells
الوصف: Cow’s milk allergy is a common food allergy, with the milk protein α S1 -casein being a major allergen. This study aimed to investigate differences in sensitization between cow and goat α S1 -CN. Cow and goat α S1 -CN were labeled with fluorescent dyes and given to mice sensitized with cholera toxin adjuvant. Both proteins reached immune organs, suggesting no major difference in digestion. However, compared with goat α S1 -CN, cow α S1 -CN is more readily taken up by dendritic cells, inducing dendritic cell maturation. Furthermore, cow α S1 -CN can more effectively induce the generation of Th2 cells, leading to a higher production of specific IgE. In a Caco-2/RBL-2H3 cell model, cow α S1 -CN caused more mast cell degranulation and loss of epithelial barrier integrity than goat α S1 -CN. In summary, this study found differences in immune responses between cow and goat milk α S1 -CN. Cow α S1 -CN elicited stronger dendritic cell and Th2 responses, leading to increased mast cell degranulation.
الإتاحة: https://doi.org/10.1021/acs.jafc.3c07688.s001Test
https://figshare.com/articles/journal_contribution/Higher_Potential_Sensitization_of_Cow_sub_S1_sub_-Casein_over_Goat_sub_S1_sub_-Casein_in_a_Mouse_Model_due_to_Enhanced_Dendritic_Cell_Uptake_and_Activation/25077660Test -
2دورية أكاديمية
المؤلفون: Nereu Junio Cândido Oliveira, Valtair Severino dos Santos Júnior, Isabella Campolina Pierotte, Victor Augusto Teixeira Leocádio, Luiz Felipe de Andrade Santana, Gabriel Vitor de Lima Marques, Ícaro Ferrari Protti, Saulo Fehelberg Pinto Braga, Markus Kohlhoff, Túlio Resende Freitas, Adriano de Paula Sabino, Thales Kronenberger, José Eduardo Gonçalves, Susana Johann, Daniel A. Santos, Isabela da Costa César, Vinícius Gonçalves Maltarollo, Renata Barbosa Oliveira
مصطلحات موضوعية: Medicine, Microbiology, Pharmacology, Biotechnology, Evolutionary Biology, Ecology, Infectious Diseases, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Information Systems not elsewhere classified, novel antifungal agent, new therapeutical options, mic value ranging, invertebrate infection model, global health problem, obtain novel compounds, nine novel compounds, results obtained indicate, 2 cell model, 28 , synthesized compounds, potent compounds, vivo <, cryptococcus <, candida <, resistant yeast, permeability study, learning models, immunocompromised individuals, higher potency
الوصف: Opportunistic fungal infections represent a global health problem, mainly for immunocompromised individuals. New therapeutical options are needed since several fungal strains show resistance to clinically available antifungal agents. 2-Thiazolylhydrazones are well-known as potent compounds against Candida and Cryptococcus species. A scaffold-focused drug design using machine-learning models was established to optimize the 2-thiazolylhydrazone skeleton and obtain novel compounds with higher potency, better solubility in water, and enhanced absorption. Twenty-nine novel compounds were obtained and most showed low micromolar MIC values against different species of Candida and Cryptococcus spp., including Candida auris, an emerging multidrug-resistant yeast. Among the synthesized compounds, 2-thiazolylhydrazone 28 (MIC value ranging from 0.8 to 52.17 μM) was selected for further studies: cytotoxicity evaluation, permeability study in Caco-2 cell model, and in vivo efficacy against Cryptococcus neoformans in an invertebrate infection model. All results obtained indicate the great potential of 28 as a novel antifungal agent.
الإتاحة: https://doi.org/10.1021/acs.jmedchem.3c01105.s001Test
https://figshare.com/articles/journal_contribution/Discovery_of_Lead_2_Thiazolylhydrazones_with_Broad-Spectrum_and_Potent_Antifungal_Activity/24774580Test -
3دورية أكاديمية
المؤلفون: Zheng-Kui Weng, Te-Hsien Lin, Kuo-Hsuan Chang, Ya-Jen Chiu, Chih-Hsin Lin, Pei-Hsuan Tseng, Ying-Chieh Sun, Wenwei Lin, Guey-Jen Lee-Chen, Chiung-Mei Chen
المصدر: Biomolecules, Vol 13, Iss 2, p 219 (2023)
مصطلحات موضوعية: Alzheimer’s disease, BDNF-TRKB signaling, TRKB agonist, heterocyclic compound, Tau cell model, Microbiology, QR1-502
الوصف: Misfolded aggregation of the hyperphosphorylated microtubule binding protein Tau in the brain is a pathological hallmark of Alzheimer’s disease (AD). Tau aggregation downregulates brain-derived neurotrophic factor (BDNF)/tropomycin receptor kinase B (TRKB) signaling and leads to neurotoxicity. Therefore, enhancement of BDNF/TRKB signaling could be a strategy to alleviate Tau neurotoxicity. In this study, eight compounds were evaluated for the potential of inhibiting Tau misfolding in human neuroblastoma SH-SY5Y cells expressing the pro-aggregator Tau folding reporter (ΔK280 Tau RD -DsRed). Among them, coumarin derivative ZN-015 and quinoline derivatives VB-030 and VB-037 displayed chemical chaperone activity to reduce ΔK280 Tau RD aggregation and promote neurite outgrowth. Studies of TRKB signaling revealed that ZN-015, VB-030 and VB-037 treatments significantly increased phosphorylation of TRKB and downstream Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), extracellular signal-regulated kinase 1/2 (ERK) and AKT serine/threonine kinase (AKT), to activate ribosomal S6 kinase (RSK) and cAMP response element-binding protein (CREB). Subsequently, p-CREB enhanced the transcription of pro-survival BDNF and BCL2 apoptosis regulator (BCL2), accompanied with reduced expression of anti-survival BCL2-associated X protein (BAX) in ΔK280 Tau RD -DsRed-expressing cells. The neurite outgrowth promotion effect of ZN-015, VB-030 and VB-037 was counteracted by a RNA interference-mediated knockdown of TRKB, suggesting the role of these compounds acting as TRKB agonists. Tryptophan fluorescence quenching analysis showed that ZN-015, VB-030 and VB-037 interacted directly with a Pichia pastoris -expressed TRKB extracellular domain, indirectly supporting the role through TRKB signaling. The results of up-regulation in TRKB signaling open up the therapeutic potentials of ZN-015, VB-030 and VB-037 for AD.
العلاقة: https://www.mdpi.com/2218-273X/13/2/219Test; https://doaj.org/toc/2218-273XTest; https://doaj.org/article/9934b3950a89424da630b45ecdf060e8Test
الإتاحة: https://doi.org/10.3390/biom13020219Test
https://doaj.org/article/9934b3950a89424da630b45ecdf060e8Test -
4دورية أكاديمية
المؤلفون: Ruggiero Gorgoglione, Roberta Seccia, Amer Ahmed, Angelo Vozza, Loredana Capobianco, Alessia Lodi, Federica Marra, Eleonora Paradies, Luigi Palmieri, Vincenzo Coppola, Vincenza Dolce, Giuseppe Fiermonte
المصدر: Biomolecules, Vol 13, Iss 5, p 808 (2023)
مصطلحات موضوعية: N -acetylglutamate, urea cycle, mitochondrial carriers, yeast cell model, Microbiology, QR1-502
الوصف: The human mitochondrial carrier family (MCF) consists of 53 members. Approximately one-fifth of them are still orphans of a function. Most mitochondrial transporters have been functionally characterized by reconstituting the bacterially expressed protein into liposomes and transport assays with radiolabeled compounds. The efficacy of this experimental approach is constrained to the commercial availability of the radiolabeled substrate to be used in the transport assays. A striking example is that of N -acetylglutamate (NAG), an essential regulator of the carbamoyl synthetase I activity and the entire urea cycle. Mammals cannot modulate mitochondrial NAG synthesis but can regulate the levels of NAG in the matrix by exporting it to the cytosol, where it is degraded. The mitochondrial NAG transporter is still unknown. Here, we report the generation of a yeast cell model suitable for identifying the putative mammalian mitochondrial NAG transporter. In yeast, the arginine biosynthesis starts in the mitochondria from NAG which is converted to ornithine that, once transported into cytosol, is metabolized to arginine. The deletion of ARG8 makes yeast cells unable to grow in the absence of arginine since they cannot synthetize ornithine but can still produce NAG. To make yeast cells dependent on a mitochondrial NAG exporter, we moved most of the yeast mitochondrial biosynthetic pathway to the cytosol by expressing four E. coli enzymes, argB-E , able to convert cytosolic NAG to ornithine. Although argB-E rescued the arginine auxotrophy of arg 8∆ strain very poorly, the expression of the bacterial NAG synthase ( argA ), which would mimic the function of a putative NAG transporter increasing the cytosolic levels of NAG, fully rescued the growth defect of arg 8∆ strain in the absence of arginine, demonstrating the potential suitability of the model generated.
العلاقة: https://www.mdpi.com/2218-273X/13/5/808Test; https://doaj.org/toc/2218-273XTest; https://doaj.org/article/dbbce2b9f7c34c37bf9fdd955f3125d4Test
الإتاحة: https://doi.org/10.3390/biom13050808Test
https://doaj.org/article/dbbce2b9f7c34c37bf9fdd955f3125d4Test -
5دورية أكاديمية
المؤلفون: Eloïne Bestion, Philippe Halfon, Soraya Mezouar, Jean-Louis Mège
المصدر: Viruses, Vol 14, Iss 1507, p 1507 (2022)
مصطلحات موضوعية: SARS-CoV-2, COVID-19, cell model, animal model, drug, Microbiology, QR1-502
الوصف: During the last two years following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, development of potent antiviral drugs and vaccines has been a global health priority. In this context, the understanding of virus pathophysiology, the identification of associated therapeutic targets, and the screening of potential effective compounds have been indispensable advancements. It was therefore of primary importance to develop experimental models that recapitulate the aspects of the human disease in the best way possible. This article reviews the information concerning available SARS-CoV-2 preclinical models during that time, including cell-based approaches and animal models. We discuss their evolution, their advantages, and drawbacks, as well as their relevance to drug effectiveness evaluation.
العلاقة: https://www.mdpi.com/1999-4915/14/7/1507Test; https://doaj.org/toc/1999-4915Test; https://doaj.org/article/8b40305c9b33477fa3813abc771631afTest
الإتاحة: https://doi.org/10.3390/v14071507Test
https://doaj.org/article/8b40305c9b33477fa3813abc771631afTest -
6دورية أكاديمية
المؤلفون: Larissa E. C. Constant, Bia F. Rajsfus, Pedro H. Carneiro, Tháyna Sisnande, Ronaldo Mohana-Borges, Diego Allonso
المصدر: Frontiers in Microbiology, Vol 12 (2021)
مصطلحات موضوعية: chikungunya virus, epidemiology, pathogenesis, in vitro cell model, rodent models, non-human primate models, Microbiology, QR1-502
الوصف: Chikungunya virus (CHIKV) is currently one of the most relevant arboviruses to public health. It is a member of the Togaviridae family and alphavirus genus and causes an arthritogenic disease known as chikungunya fever (CHIKF). It is characterized by a multifaceted disease, which is distinguished from other arbovirus infections by the intense and debilitating arthralgia that can last for months or years in some individuals. Despite the great social and economic burden caused by CHIKV infection, there is no vaccine or specific antiviral drugs currently available. Recent outbreaks have shown a change in the severity profile of the disease in which atypical and severe manifestation lead to hundreds of deaths, reinforcing the necessity to understand the replication and pathogenesis processes. CHIKF is a complex disease resultant from the infection of a plethora of cell types. Although there are several in vivo models for studying CHIKV infection, none of them reproduces integrally the disease signature observed in humans, which is a challenge for vaccine and drug development. Therefore, understanding the potentials and limitations of the state-of-the-art experimental models is imperative to advance in the field. In this context, the present review outlines the present knowledge on CHIKV epidemiology, replication, pathogenesis, and immunity and also brings a critical perspective on the current in vitro and in vivo state-of-the-art experimental models of CHIKF.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2021.744164/fullTest; https://doaj.org/toc/1664-302XTest
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7دورية أكاديمية
المؤلفون: Xin Yan, Sen Hu, Yan Yang, Da Xu, Wenxing Liu, Ganwu Li, Wentong Cai, Zhigao Bu
المصدر: Frontiers in Cellular and Infection Microbiology, Vol 11 (2021)
مصطلحات موضوعية: Brucella melitensis, twin-arginine protein translocation, immune response, RAW264.7 cell model, cytokines, nitric oxide - NO, Microbiology, QR1-502
الوصف: Brucella, a notorious intracellular pathogen, causes chronic infections in many mammals, including humans. The twin-arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane; protein substrates translocated by Brucella include ABC transporters, oxidoreductases, and cell envelope biosynthesis proteins. Previously, we showed that a Tat mutant of Brucella melitensis M28 exhibits reduced survival within murine macrophages. In this study, we compared the host responses elicited by wild-type M28 and its Tat-mutant strains ex vivo. We utilized label-free quantitative proteomics to assess proteomic changes in RAW264.7 macrophages after infection with M28 and its Tat mutants. A total of 6085 macrophage proteins were identified with high confidence, and 79, 50, and 99 proteins were differentially produced upon infection with the Tat mutant at 4, 24, and 48 hpi, respectively, relative to the wild-type infection. Gene ontology and KEGG enrichment analysis indicated that immune response-related proteins were enriched among the upregulated proteins. Compared to the wild-type M28 infection, the most upregulated proteins upon Tat-mutant infection included the cytosolic nucleic acid signaling pathway-related proteins IFIH1, DHX58, IFI202, IFI204, and ISG15 and the NF-κB signaling pathway-related proteins PTGS2, CD40, and TRAF1, suggesting that the host increases the production of these proteins in response to Tat mutant infection. Upregulation of some proteins was further verified by a parallel reaction monitoring (PRM) assay. ELISA and qRT-PCR assays indicated that Tat mutant infection significantly induced proinflammatory cytokine (TNF-α and IL-6) and nitric oxide (NO) production. Finally, we showed that the Tat mutant displays higher sensitivity to nitrosative stress than the wild type and that treatment with the NO synthase inhibitor L-NMMA significantly increases the intracellular survival of the Tat mutant, indicating that NO production contributes to restricting Tat mutant survival within macrophages. Collectively, this work improves our understanding of host immune responses to Tat mutants and provides insights into the mechanisms underlying the attenuated virulence of Tat mutants.
وصف الملف: electronic resource
العلاقة: https://www.frontiersin.org/articles/10.3389/fcimb.2021.679571/fullTest; https://doaj.org/toc/2235-2988Test
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8دورية أكاديمية
المؤلفون: Connie Le (8463771), Yanming Liu (1482403), Joaquín López-Orozco (11210140), Michael A. Joyce (9694450), X. Chris Le (17762), D. Lorne Tyrrell (17808)
مصطلحات موضوعية: Biophysics, Microbiology, Cell Biology, Genetics, Molecular Biology, Immunology, Developmental Biology, Cancer, Infectious Diseases, Virology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, CRISPR Technique Incorporated, liver cell model, CRISPR-Cas 9 technique, hepatitis B virus, HBV infection, HBV RNA, HBV-infected Huh 7.5-NTCP cells, Huh 7.5-NTCP cells, Hepatitis B Infection, gene expression, CRISPR-mediated enrichment technique, Single-Cell RNA Sequencing, cell RNA-seq analysis, transcript
الوصف: Single-cell RNA sequencing (scRNA-seq) provides rich transcriptomic information for studying molecular events and cell heterogeneity at the single-cell level. However, it is challenging to obtain sequence information from rare or low-abundance genes in the presence of other highly abundant genes. We report here a CRISPR-Cas9 technique for the depletion of high-abundance transcripts, resulting in preferential enrichment of rare transcripts. We demonstrate an application of this CRISPR-mediated enrichment technique to scRNA-seq of liver cells infected with hepatitis B virus (HBV). Direct sequencing without the CRISPR-mediated enrichment detected HBV RNA in only 0.6% of the cells. The CRISPR-mediated depletion of the three most abundant transcripts resulted in selective enrichment of the HBV transcript and successful sequencing of HBV RNA in more than 74% of the cells. The improvement enabled a study of HBV infection and interferon treatment of a liver cell model. Gene clusters between the control and HBV-infected Huh7.5-NTCP cells were similar, suggesting that HBV infection did not significantly alter gene expression of the host cells. The treatment with interferon alpha dramatically changed the gene expression of Huh7.5-NTCP cells. These results from the single cell RNA-seq analysis of 7370 cells are consistent with those of bulk experiments, suggesting that HBV is a “stealth virus”.
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9دورية أكاديمية
المؤلفون: E. M. Keizer (11105218), I. D. Valdes (11105221), G. Forn-Cuni (11105224), E. Klijn (11105227), A. H. Meijer (7605770), F. Hillman (11105230), H. A. B. Wösten (11105233), H. de Cock (11105236)
مصطلحات موضوعية: Medicine, Microbiology, Evolutionary Biology, Ecology, Immunology, Infectious Diseases, Virology, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Protostelium aurantium amoeba, genome sequence analysis, Galleria melonella larvae, infection models Conidia, SNP, lung epithelial cell model, Galleria infection model, Aspergillus fumigatus, CEA, 549 lung epithelial cells, strain ATCC 46645, DTO 303-F, aspergillosi, fumigatus strains show, reference strain Af 293, virulence, 271-B, infection models, model systems, II, infection model systems
الوصف: Green cells represent cells that are alive (L), where the acridine orange can bind the double stranded DNA. Orange cells are apoptotic cells (A), where the acridine orange can bind the RNA or single stranded DNA. Red cells are cells where the ethidium bromide can enter indicating that they are necrotic (N). (DOCX)
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10دورية أكاديمية
المؤلفون: E. M. Keizer (11105218), I. D. Valdes (11105221), G. Forn-Cuni (11105224), E. Klijn (11105227), A. H. Meijer (7605770), F. Hillman (11105230), H. A. B. Wösten (11105233), H. de Cock (11105236)
مصطلحات موضوعية: Medicine, Microbiology, Evolutionary Biology, Ecology, Immunology, Infectious Diseases, Virology, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Protostelium aurantium amoeba, genome sequence analysis, Galleria melonella larvae, infection models Conidia, SNP, lung epithelial cell model, Galleria infection model, Aspergillus fumigatus, CEA, 549 lung epithelial cells, strain ATCC 46645, DTO 303-F, aspergillosi, fumigatus strains show, reference strain Af 293, virulence, 271-B, infection models, model systems, II, infection model systems
الوصف: Representative images of association (A and B), conidia are shown in red (A) and A459 cells are stained with Hoechst and shown in blue(B), and internalization (C and D), conidia are shown in red (C) and conidia also stained with CalcoFluor White (CFW) in blue (D) are considered to be outside of the A549 cells, after 4 h of incubation. (DOCX)
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