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  1. Artikel ; Online: Modifier pathways in polyglutamine (PolyQ) diseases: from genetic screens to drug targets.

    Costa, Marta Daniela / Maciel, Patrícia

    Cellular and molecular life sciences : CMLS

    2022  Band 79, Heft 5, Seite(n) 274

    Abstract: Polyglutamine (PolyQ) diseases include a group of inherited neurodegenerative disorders caused by unstable expansions of CAG trinucleotide repeats in the coding region of specific genes. Such genetic alterations produce abnormal proteins containing an ... ...

    Abstract Polyglutamine (PolyQ) diseases include a group of inherited neurodegenerative disorders caused by unstable expansions of CAG trinucleotide repeats in the coding region of specific genes. Such genetic alterations produce abnormal proteins containing an unusually long PolyQ tract that renders them more prone to aggregate and cause toxicity. Although research in the field in the last years has contributed significantly to the knowledge of the biological mechanisms implicated in these diseases, effective treatments are still lacking. In this review, we revisit work performed in models of PolyQ diseases, namely the yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and provide a critical overview of the high-throughput unbiased genetic screens that have been performed using these systems to identify novel genetic modifiers of PolyQ diseases. These approaches have revealed a wide variety of cellular processes that modulate the toxicity and aggregation of mutant PolyQ proteins, reflecting the complexity of these disorders and demonstrating how challenging the development of therapeutic strategies can be. In addition to the unbiased large-scale genetic screenings in non-vertebrate models, complementary studies in mammalian systems, closer to humans, have contributed with novel genetic modifiers of PolyQ diseases, revealing neuronal function and inflammation as key disease modulators. A pathway enrichment analysis, using the human orthologues of genetic modifiers of PolyQ diseases clustered modifier genes into major themes translatable to the human disease context, such as protein folding and transport as well as transcription regulation. Innovative genetic strategies of genetic manipulation, together with significant advances in genomics and bioinformatics, are taking modifier genetic studies to more realistic disease contexts. The characterization of PolyQ disease modifier pathways is of extreme relevance to reveal novel therapeutic possibilities to delay disease onset and progression in patients.
    Mesh-Begriff(e) Animals ; Caenorhabditis elegans/metabolism ; Drosophila/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Genetic Testing ; Humans ; Mammals/genetics ; Mutant Proteins/metabolism ; Peptides/metabolism ; Saccharomyces cerevisiae/metabolism
    Chemische Substanzen Mutant Proteins ; Peptides ; polyglutamine (26700-71-0)
    Sprache Englisch
    Erscheinungsdatum 2022-05-03
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04280-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Modifier pathways in polyglutamine (PolyQ) diseases: from genetic screens to drug targets

    Costa, Marta Daniela / Maciel, Patrícia

    Cellular and molecular life sciences. 2022 May, v. 79, no. 5

    2022  

    Abstract: Polyglutamine (PolyQ) diseases include a group of inherited neurodegenerative disorders caused by unstable expansions of CAG trinucleotide repeats in the coding region of specific genes. Such genetic alterations produce abnormal proteins containing an ... ...

    Abstract Polyglutamine (PolyQ) diseases include a group of inherited neurodegenerative disorders caused by unstable expansions of CAG trinucleotide repeats in the coding region of specific genes. Such genetic alterations produce abnormal proteins containing an unusually long PolyQ tract that renders them more prone to aggregate and cause toxicity. Although research in the field in the last years has contributed significantly to the knowledge of the biological mechanisms implicated in these diseases, effective treatments are still lacking. In this review, we revisit work performed in models of PolyQ diseases, namely the yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and provide a critical overview of the high-throughput unbiased genetic screens that have been performed using these systems to identify novel genetic modifiers of PolyQ diseases. These approaches have revealed a wide variety of cellular processes that modulate the toxicity and aggregation of mutant PolyQ proteins, reflecting the complexity of these disorders and demonstrating how challenging the development of therapeutic strategies can be. In addition to the unbiased large-scale genetic screenings in non-vertebrate models, complementary studies in mammalian systems, closer to humans, have contributed with novel genetic modifiers of PolyQ diseases, revealing neuronal function and inflammation as key disease modulators. A pathway enrichment analysis, using the human orthologues of genetic modifiers of PolyQ diseases clustered modifier genes into major themes translatable to the human disease context, such as protein folding and transport as well as transcription regulation. Innovative genetic strategies of genetic manipulation, together with significant advances in genomics and bioinformatics, are taking modifier genetic studies to more realistic disease contexts. The characterization of PolyQ disease modifier pathways is of extreme relevance to reveal novel therapeutic possibilities to delay disease onset and progression in patients.
    Schlagwörter Caenorhabditis elegans ; Drosophila melanogaster ; Saccharomyces cerevisiae ; bioinformatics ; fruit flies ; genetic engineering ; genomics ; human diseases ; humans ; inflammation ; mutants ; neurons ; therapeutics ; toxicity ; transcription (genetics) ; yeasts
    Sprache Englisch
    Erscheinungsverlauf 2022-05
    Umfang p. 274.
    Erscheinungsort Springer International Publishing
    Dokumenttyp Artikel
    Anmerkung Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-022-04280-8
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  3. Artikel: Anorexia Nervosa and Osteoporosis: A Possible Complication to Remember.

    Rosas Pereira, André / Costa, Marta / Costa, Gustavo G / Carvalho, Ana Sofia

    Cureus

    2024  Band 16, Heft 1, Seite(n) e52670

    Abstract: Anorexia nervosa (AN) belongs to the spectrum of food disorders and affects approximately 2.9 million people worldwide. It is responsible for numerous and serious medical complications. Osteoporosis is a common complication, and the decrease in bone ... ...

    Abstract Anorexia nervosa (AN) belongs to the spectrum of food disorders and affects approximately 2.9 million people worldwide. It is responsible for numerous and serious medical complications. Osteoporosis is a common complication, and the decrease in bone mineral density (BMD) is one of the few potentially irreversible consequences of AN. When associated with AN, it can manifest at a very young age, possibly leading to irreparable damage. We describe the case of a 30-year-old woman with a one-year evolution diagnosis of AN, complaining of back pain. Physical examination revealed a slight elevation of the right shoulder and pain at compression of paravertebral right dorsal musculature with a palpable strained muscle. Full-length X-ray imaging of the dorsal spine revealed a slight dextroconvex dorsolumbar scoliosis. A dorsal spine computerized tomography (CT) was performed, confirming a fracture of the upper platform of the sixth dorsal vertebrae. Osteodensitometry showed lumbar spine osteoporosis and femoral osteopenia. The decrease in BMD and, later on, the development of osteoporosis can occur in both types of AN. It is a severe complication that affects up to 50% of these patients. It can be irreversible and increase the lifetime risk of bone fractures and, therefore, morbimortality. Low body weight and body mass index (BMI) strongly correlate with the decrease in BMD. Treatment of osteoporosis associated with AN is not standardized and clearly labeled. Weight gain is described as the strategy with the most impact in reversing the loss of bone mass and increasing the BMD. The regularization of gonadal function also seems to independently potentiate the increase of BMD. The occurrence of long bone and vertebrae fractures frequently results in a decrease in height and chronic back pain, culminating in greater morbimortality and healthcare costs. This clinical case aims to show theclose relationship between restrictive food disorders and the decrease of BMD and the subsequent development of osteoporosis and its complications. Although rare in young and healthy people, when associated with restrictive food disorders, it should raise a red flag in its clinical evaluation. Preventing osteoporosis development and reduction of fracture risk in this population is essential. The current absence of consistent evidence regarding screening of osteoporosis in this particular group should raise awareness and promote further larger-scale studies to establish standardized recommendations concerning not only screening but also pharmacological treatment of osteoporosis in patients with AN.
    Sprache Englisch
    Erscheinungsdatum 2024-01-21
    Erscheinungsland United States
    Dokumenttyp Case Reports
    ZDB-ID 2747273-5
    ISSN 2168-8184
    ISSN 2168-8184
    DOI 10.7759/cureus.52670
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Longitudinal tracking of diet quality from childhood to adolescence: The Interplay of individual and sociodemographic factors.

    da Costa, Marta Pinto / Severo, Milton / Araújo, Joana / Vilela, Sofia

    Appetite

    2024  Band 196, Seite(n) 107279

    Abstract: This study aimed to examine diet tracking from childhood to adolescence, using 4 time-points, and the influence of socioeconomic and individual characteristics in this transition. The sample included 6893 children from the Portuguese birth cohort ... ...

    Abstract This study aimed to examine diet tracking from childhood to adolescence, using 4 time-points, and the influence of socioeconomic and individual characteristics in this transition. The sample included 6893 children from the Portuguese birth cohort Generation XXI with complete information on Food Frequency Questionnaire in at least one of the considered follow-ups. A Healthy Eating Index (HEI), previously developed to assess adherence to WHO's dietary recommendations, was applied at all ages (4, 7, 10 and 13y). The intraclass correlation coefficient (ICC) was used to analyse the tracking of diet quality. Linear mixed-effect models were performed to estimate the association of the child's socioeconomic and individual characteristics with the HEI score and respective trajectories over time. The overall diet quality decreased from childhood (22.2 ± 3.6 at 4y) to adolescence (18.2 ± 3.9 at 13y), with moderate tracking (ICC = 0.53), showing that children who start a healthy diet earlier might have a better diet quality as time goes by. Children of older mothers (β = 0.079, 95%CI = 0.061-0.097) and with higher education (β = 0.203, 95%CI = 0.178-0.229) and a higher household monthly income (β = 0.024,95%CI = 0.007-0.041) had a higher diet quality over time. Besides family characteristics, the child's sedentary activities (β = -0.009, 95%CI = -0.014--0.003) negatively influence diet quality throughout life. In contrast, being a girl (β = -0.094, 95%CI = -0.132--0.056) and having higher sleep duration (β = 0.039, 95%CI = 0.015-0.064) are associated with a higher diet quality over time. The presence of dietary tracking from childhood to adolescence implies that promoting healthy eating habits during the first years of life is crucial for a healthier diet quality during late childhood and early adolescence, focusing on maternal and individual child characteristics.
    Mesh-Begriff(e) Female ; Child ; Humans ; Adolescent ; Sociodemographic Factors ; Diet ; Diet, Healthy ; Mothers ; Feeding Behavior
    Sprache Englisch
    Erscheinungsdatum 2024-02-22
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 1461347-5
    ISSN 1095-8304 ; 0195-6663
    ISSN (online) 1095-8304
    ISSN 0195-6663
    DOI 10.1016/j.appet.2024.107279
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: May-Thurner Syndrome: The Worst-Case Scenario.

    Costa, Marta / Ferreira, Gonçalo / Gomes, Dora / Oliveira, Catarina / Domingues, Nelson

    Cureus

    2024  Band 16, Heft 3, Seite(n) e55742

    Abstract: May-Thurner syndrome (MTS) is caused by compression of the left common iliac vein by the right common iliac artery against the spinal column. It can range from asymptomatic or present with subtle and unspecific signs and symptoms and rarely exhibit ... ...

    Abstract May-Thurner syndrome (MTS) is caused by compression of the left common iliac vein by the right common iliac artery against the spinal column. It can range from asymptomatic or present with subtle and unspecific signs and symptoms and rarely exhibit severe complications such as pulmonary embolism (PE). The diagnosis is confirmed by typical imaging findings. Treatment may include conservative measures, anticoagulation, endovascular or even surgical options. We report the case of a 20-year-old female who presented with cardiac arrest caused by an acute massive PE. Further study showed partial thrombosis of the internal iliac veins resulting from MTS. She continued anticoagulation therapy with low-molecular-weight heparin and then switched to edoxaban with a good clinical outcome. She was also referred to Vascular Surgery to discuss the possibility of iliac vein stenting. Abdominopelvic vascular compression syndromes include a large spectrum of conditions, and they are rarely considered as an etiology for venous thromboembolism. The clinical presentation of PE varies with several triggering factors and atypical presentation is more common in nonmalignant causes. The combination of noninvasive and invasive imaging modalities might be beneficial to establish a definitive diagnosis. Nevertheless, invasive procedures are often restricted to doubtful cases or to guide endovascular procedures which is the current treatment of choice. There is little evidence using nonvitamin K oral anticoagulants, but there are some case reports detailing their successful use. This case aims to point out the need for a profound understanding of different causes of deep vein and pulmonary thromboembolism; common entities in our practice but with a variety of clinical presentations and potentially caused by rare underlying conditions. MTS can be the origin of serious and deadly complications, hence the importance of early recognition and treatment.
    Sprache Englisch
    Erscheinungsdatum 2024-03-07
    Erscheinungsland United States
    Dokumenttyp Case Reports
    ZDB-ID 2747273-5
    ISSN 2168-8184
    ISSN 2168-8184
    DOI 10.7759/cureus.55742
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: A roadmap towards manufacturing extracellular vesicles for cardiac repair.

    Louro, Ana F / Meliciano, Ana / Alves, Paula M / Costa, Marta H G / Serra, Margarida

    Trends in biotechnology

    2024  

    Abstract: For the past two decades researchers have linked extracellular vesicle (EV)-mediated mechanisms to various physiological and pathological processes in the heart, such as immune response regulation, fibrosis, angiogenesis, and the survival and growth of ... ...

    Abstract For the past two decades researchers have linked extracellular vesicle (EV)-mediated mechanisms to various physiological and pathological processes in the heart, such as immune response regulation, fibrosis, angiogenesis, and the survival and growth of cardiomyocytes. Although use of EVs has gathered momentum in the cardiac field, several obstacles in both upstream and downstream processes during EV manufacture need to be addressed before clinical success can be achieved. Low EV yields obtained in small-scale cultures deter clinical translation, as mass production is a prerequisite to meet therapeutic doses. Moreover, standardizing EV manufacture is critical given the inherent heterogeneity of EVs and the constraints of current isolation techniques. In this review, we discuss the critical steps for the large-scale manufacturing of high-potency EVs for cardiac therapies.
    Sprache Englisch
    Erscheinungsdatum 2024-04-22
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 47474-5
    ISSN 1879-3096 ; 0167-7799
    ISSN (online) 1879-3096
    ISSN 0167-7799
    DOI 10.1016/j.tibtech.2024.03.010
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Mapping of the zebrafish brain takes shape.

    Brooks, Paul / Champion, Andrew / Costa, Marta

    Nature methods

    2022  Band 19, Heft 11, Seite(n) 1345–1346

    Mesh-Begriff(e) Animals ; Zebrafish/metabolism ; Brain/metabolism ; Brain Mapping ; Head ; Zebrafish Proteins/metabolism
    Chemische Substanzen Zebrafish Proteins
    Sprache Englisch
    Erscheinungsdatum 2022-10-22
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-022-01637-6
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Connectomics and the neural basis of behaviour.

    Galili, Dana S / Jefferis, Gregory Sxe / Costa, Marta

    Current opinion in insect science

    2022  Band 54, Seite(n) 100968

    Abstract: Methods to acquire and process synaptic-resolution electron-microscopy datasets have progressed very rapidly, allowing production and annotation of larger, more complete connectomes. More accurate neuronal matching techniques are enriching cell type data ...

    Abstract Methods to acquire and process synaptic-resolution electron-microscopy datasets have progressed very rapidly, allowing production and annotation of larger, more complete connectomes. More accurate neuronal matching techniques are enriching cell type data with gene expression, neuron activity, behaviour and developmental information, providing ways to test hypotheses of circuit function. In a variety of behaviours such as learned and innate olfaction, navigation and sexual behaviour, connectomics has already revealed interconnected modules with a hierarchical structure, recurrence and integration of sensory streams. Comparing individual connectomes to determine which circuit features are robust and which are variable is one key research area; new work in comparative connectomics across development, experience, sex and species will establish strong links between neuronal connectivity and brain function.
    Mesh-Begriff(e) Animals ; Connectome/methods ; Nervous System ; Neurons/physiology ; Smell
    Sprache Englisch
    Erscheinungsdatum 2022-09-13
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2772833-X
    ISSN 2214-5753 ; 2214-5745
    ISSN (online) 2214-5753
    ISSN 2214-5745
    DOI 10.1016/j.cois.2022.100968
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: The effect of non-absorbent hydrophobic sand litter on the urine protein-to-creatinine ratio in feline urine.

    Kennils, Josh M / Maunder, Christina L / Costa, Marta T

    Veterinary clinical pathology

    2022  Band 51, Heft 3, Seite(n) 385–390

    Abstract: Background: Proteinuria can be quantified through the measurement of the urine protein-to-creatinine ratio (UPC). Voided urine samples in cats are often exposed to a non-absorbable litter substrate prior to collection and urinalysis. Little is known ... ...

    Abstract Background: Proteinuria can be quantified through the measurement of the urine protein-to-creatinine ratio (UPC). Voided urine samples in cats are often exposed to a non-absorbable litter substrate prior to collection and urinalysis. Little is known about the effect exposure to such substrates has on pre-analytical variability of UPC measurements.
    Objectives: The aim of this study was to assess agreement between UPC measurements from urine obtained by cystocentesis before and after exposure to non-absorbent hydrophobic sand for 24 hours.
    Methods: UPCs were measured in 40 urine samples obtained by cystocentesis from 39 cats (baselineUPC). Urine was then exposed to non-absorbent hydrophobic sand litter for 24 hours, recovered, and repeat UPCs were measured (litterUPC). Agreement between paired measurements and the presence of any bias or error was evaluated using Bland-Altman analysis Passing-Bablok regression analysis, respectively. Cohen's kappa was used to measure agreement for the International Renal Interest Society (IRIS) proteinuria classification of samples. Observed total error (TE
    Results: Neither proportional nor constant error was identified using Passing-Bablok regression between baselineUPC and litterUPC. Visual inspection of the Bland-Altman plot revealed good agreement, with 95% of paired measures falling within the limits of agreement (LOA). Cohen's kappa demonstrated almost perfect agreement for the IRIS classification of proteinuria between baselineUPC and litterUPC. Absolute percentage changes of paired UPC measurements outside of the LOAs were lower than the inter-assay TE
    Conclusions: Feline urine exposed to non-absorbent hydrophobic sand litter appears acceptable for UPC measurements.
    Mesh-Begriff(e) Animals ; Cat Diseases/urine ; Cats ; Creatinine/urine ; Proteinuria/urine ; Proteinuria/veterinary ; Sand ; Urinalysis/veterinary
    Chemische Substanzen Sand ; Creatinine (AYI8EX34EU)
    Sprache Englisch
    Erscheinungsdatum 2022-04-01
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2114702-4
    ISSN 1939-165X ; 0275-6382
    ISSN (online) 1939-165X
    ISSN 0275-6382
    DOI 10.1111/vcp.13110
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  10. Artikel ; Online: In vitro

    Carvalho, Luísa / de Lima, Fábio Pedroso / Cerqueira, Mónica / Silva, Ana / Pontes, Olívia / Oliveira-Pinto, Sofia / Guerreiro, Sara / Costa, Marta D / Granja, Sara / Maciel, Patrícia / Longatto-Filho, Adhemar / Baltazar, Fátima / Proença, Fernanda / Costa, Marta

    RSC medicinal chemistry

    2024  Band 15, Heft 4, Seite(n) 1362–1380

    Abstract: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the limited therapeutic options show poor efficacy in patients, associated to severe side effects and development of resistance. Considering that chromene-based ... ...

    Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the limited therapeutic options show poor efficacy in patients, associated to severe side effects and development of resistance. Considering that chromene-based scaffolds proved to be attractive candidates for cancer therapy, herein we prepared new chromeno[2,3-
    Sprache Englisch
    Erscheinungsdatum 2024-03-19
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 2632-8682
    ISSN (online) 2632-8682
    DOI 10.1039/d3md00682d
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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