Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Babesiosis. Core disease mechanisms, molecular and cellular pathways, invo...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 20
• Snippets retrieved: 20

Relevant Papers

[1] Babesia microti: Pathogen Genomics, Genetic Variability, Immunodominant Antigens, and Pathogenesis

• Authors: Ankit Puri, S. Bajpai, S. Meredith, L. Aravind, P. Krause et al.
• Year: 2021
• Venue: Frontiers in Microbiology
• URL: https://www.semanticscholar.org/paper/2190fcd52b2b7e5a448fccea5b00ac8f1067461a
• DOI: 10.3389/fmicb.2021.697669
• PMID: 34539601
• PMCID: 8446681
• Citations: 40
• Influential citations: 1
• Summary: More than 100 Babesia spp. tick-borne parasites are known to infect mammalian and avian hosts. Babesia belong to Order Piroplasmid ranked in the Phylum Apicomplexa. Recent phylogenetic studies have revealed that of the three genera that constitute Piroplasmida, Babesia and Theileria are polyphyletic while Cytauxzoon is nested within a clade of Theileria. Several Babesia spp. and sub-types have been found to cause human disease. Babesia microti, the most common species that infects humans, is...
• Evidence snippets:
• Snippet 1 (score: 0.448) > The pathogenesis of Babesia spp. infections in humans is multifactorial, complex, and incompletely understood. In particular, molecular processes that underlie pathogenic mechanisms in human babesiosis have not been well researched. Pathogenesis studies are complicated by variation in pathogenic mechanisms for different Babesia spp. and variation in the immunologic status and pathophysiological response of hosts. Three clinical patterns of human babesiosis have been described: acute symptomatic disease which may be mild, moderate or severe, acute asymptomatic infection, and persistent infection (Vannier et al., 2008;Vannier and Krause, 2012). Acute asymptomatic infection is the most common clinical presentation. Asymptomatic infection occurs in about 20% of adults and is characterized by low parasitemia. Persistent infection follows acute symptomatic or asymptomatic infection and may last as long as 2 years (Krause et al., 1998(Krause et al., , 2007;;Raffalli and Wormser, 2016).

[2] Babesiosis: Appreciating the Pathophysiology and Diverse Sequela of the Infection

• Authors: J. Ortíz, Paul W. Millhouse, Álvaro Morillo Cox, Leticia Campoverde, Arveen Kaur et al.
• Year: 2020
• Venue: Cureus
• URL: https://www.semanticscholar.org/paper/a0ce001a737df3fac0d9bd8e77c62d805ec0706a
• DOI: 10.7759/cureus.11085
• PMID: 33224678
• PMCID: 7678756
• Citations: 11
• Influential citations: 1
• Summary: A better appreciation of all potential presentations and complications of Babesia microti infection will help clinicians manage this increasingly common zoonosis and reduce adverse effects.
• Evidence snippets:
• Snippet 1 (score: 0.410) > Babesiosis: Appreciating the Pathophysiology and Diverse Sequela of the Infection

[3] Canine Babesiosis and Therapy Options – A Review

• Authors: Z. Malinovská
• Year: 2024
• Venue: Folia Veterinaria
• URL: https://www.semanticscholar.org/paper/426a70cc0fab66bc533f2aa70665d10bfd6cb36e
• DOI: 10.2478/fv-2024-0017
• Citations: 5
• Summary: The clinical manifestations of babesiosis may vary depending on the particular species and strains, and their specific virulence, but also depending on factors that determine the host’s response to infection, such as age, individual immune status, and the presence of concurrent infections or other diseases.
• Evidence snippets:
• Snippet 1 (score: 0.399) > Abstract Babesiosis is a disease caused by intraerythrocytic protozoal parasites, which occurs in animals and humans. In dogs, babesiosis can be caused by eight species of Babesia gene: i.e., B. canis, B. rossi, B. vogeli, B. coco, B. gibsoni, B. conradae, B., and B. negevi, which are bound to certain geographical areas. The disease has a focal nature and its transmission depends mainly on vectors, which are ticks of various species. Due to transstadial, and transovarial transmission, babesiosis is able to persist in natural foci in several generations of ticks, even without the presence of a susceptible host. Typical clinical signs associated with canine babesiosis are: fever, apathy, weakness, pale mucous membranes, icterus and hemoglobinuria. The disease can have an acute or peracute course, and subclinical and subacute infections have also been described. The clinical manifestations of babesiosis may vary depending on the particular species and strains, and their specific virulence, but also depending on factors that determine the host’s response to infection, such as age, individual immune status, and the presence of concurrent infections or other diseases. Medicines, from the group of antiprotozoans, a selected group of antibiotics, or their combinations are used for therapy. There are differences in the therapy of babesiosis depending on the Babesia species, the animal is often cured of the acute phase, but the parasite remains in the organism.

[4] Critical role of Babesia bovis spherical body protein 3 in ridge formation on infected red blood cells

• Authors: Atefeh Fathi, Hassan Hakimi, M. Sakaguchi, Junya Yamagishi, S. Kawazu et al.
• Year: 2024
• Venue: PLOS Pathogens
• URL: https://www.semanticscholar.org/paper/489ca411819deec14b41b0716cc0408f6bebcea8
• DOI: 10.1371/journal.ppat.1012294
• PMID: 39527619
• PMCID: 11581398
• Citations: 3
• Summary: The vital role of SBP3 in ridge formation and its significance in the pathogenesis of cerebral babesiosis are revealed and light is shed on the molecular mechanism of ridge formation and the pathogenesis of B. bovis.
• Evidence snippets:
• Snippet 1 (score: 0.389) > Babesia is a tick-transmitted intraerythrocytic protozoan parasite infecting a large variety of domestic and wild animals, and sometimes humans [1]. Although more than 100 species of Babesia are known to infect mammalians, bovine Babesia parasites cause serious economic loss to cattle industries around the world [1,2]. Current control measures against bovine babesiosis are limited. Few drugs are available, and there are limitations in the usage of vaccines; moreover, resistance of the vector tick to acaricides has also become apparent recently [1][2][3]. Therefore, exploration of new control and treatment measures for the disease is urgently needed. > The two major species that cause bovine babesiosis are Babesia bovis and B. bigemina. The main clinical symptoms of bovine babesiosis are fever, anemia, and hemoglobinuria. While these symptoms are mainly caused by intravascular hemolysis and are common for B. bigemina infection, B. bovis infection adds an additional complication called cerebral babesiosis. Cytoadhesion of B. bovis-infected red blood cells (iRBCs) to brain microvascular endothelial cells leads to the sequestration of blood flow in the brain vascular system, causing cerebral symptoms and a high fatality rate in infected animals [1,4,5]. > Protrusions called "ridges" on the surface of iRBC are reported as the main sites for cytoadhesion to endothelial cells. Ridges are unique structures for B. bovis-iRBCs, and currently it is known that multiple proteins are exported from the parasites to the cytoplasm and surface of the iRBCs [6][7][8][9][10][11][12][13][14]. Although the function and export mechanisms are unknown for most of these proteins, it is thought that they contribute to enhancement of metabolite exchange, increase of RBC rigidity, and cytoadhesion to the host endothelial cells [4,7,15].

[5] LifeTime and improving European healthcare through cell-based interceptive medicine

• Authors: N. Rajewsky, G. Almouzni, S. Gorski, S. Aerts, I. Amit et al.
• Year: 2020
• Venue: Nature
• URL: https://www.semanticscholar.org/paper/d626a4acb560c1ef16ea394cb4dccf277882d119
• DOI: 10.1038/s41586-020-2715-9
• PMID: 32894860
• PMCID: 7656507
• Citations: 138
• Influential citations: 2
• Summary: The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe over the next decade.
• Evidence snippets:
• Snippet 1 (score: 0.368) > , a major challenge is a lack of understanding of the early events in disease onset to enable the development of disease-modifying therapies. The lack of access to longitudinal samples from patients necessitates the establishment of cohorts of patient-derived disease models to understand the cellular heterogeneity associated with disease. The discovery of pathways and biomarkers that will allow the stratification of patients on the basis of the cellular mechanisms that drive a disease will make it possible to design new clinical trials to reevaluate drugs that were previously tested without such stratification, and to broaden the drug target portfolio. > As seen during the coronavirus disease 2019 (COVID-19) pandemic, it is important to be able to understand infection mechanisms and the host response in order to rapidly identify the most likely effective treatment for an infection. At the same time, the continuous rise of antimicrobial resistance requires the discovery of new therapeutic strategies. A key medical challenge for infectious diseases is to understand the cellular response to infections and to develop precision, immune-based therapeutic strategies to combat infections. > Chronic inflammatory diseases impose a high burden owing to their long-term debilitating consequences, which result from the structural destruction of affected organs or tissues. Current therapies treat the symptoms but do not cure or fully control the chronic inflammatory pathophysiology. While different targeted therapies exist, they are expensive and their success is limited by high rates of non-response to treatment. Consequently, there is an urgent need to explore and understand how cellular heterogeneity contributes to the pathology of inflammatory diseases 61 and how this relates to the predicted course of disease and the response of a patient to one of the numerous available therapies. > Many cardiovascular and metabolic diseases lack effective therapies owing to a lack of knowledge of their underlying causes and the link between abnormal cardiac cell structure or function and pathophysiology. The identified medical priority is to understand the cellular and molecular mechanisms involved, in order to enable early diagnosis and the design of new mechanism-based therapies for precise clinical treatment. > The LifeTime disease roadmaps can be divided broadly into three phases 7 : first, immediate research into the identified medical challenges using established, scaled single-cell technologies, computational tools and disease models; second, the development of new technologies that are required

[6] Acid-base status in canine babesiosis caused by Babesia canis

• Authors: M. Torti, J. Kuleš, V. Matijatko, M. Brkljačić, I. Kiš et al.
• Year: 2020
• Venue: Unknown venue
• URL: https://www.semanticscholar.org/paper/2338148ace14ba6c54fe80dba8922cd464779dd6
• DOI: 10.24099/vet.arhiv.1230
• Citations: 4
• Summary: The objective of this study was to determine the acid-base status, blood gases and electrolyte concentrations in naturally occurring canine babesiosis caused by B. canis, and to compare the results to those in healthy dogs.
• Evidence snippets:
• Snippet 1 (score: 0.365) > Canine babesiosis is a tick-borne disease caused by the hemoprotozoan parasites of the genus Babesia (TABOADA and MERCHANT, 1991). Babesia parasites are classified either as large or small Babesia (KUTTLER, 1988). The large Babesia include four different species, namely, Babesia canis (B. canis), B. rossi, B. vogeli, which were earlier classified as subspecies of B. canis (UILENBERG et al., 1989;SCHETTERS, 2005), and Babesia sp. (Coco) (BIRKENHEUER et al., 2004;LEHTINEN et al., 2008). Thus far, several small Babesia have been identified: B. gibsoni, B. conradae, and "Babesia vulpes", a name suggested depression, splenomegaly, and hyperkinetic pulse (LOBETTI, 1998;KOSTER et al., 2015). The prognosis of the uncomplicated form is good to excellent, if treated properly with antibabesial drugs (MATIJATKO et al., 2005). The complicated form of canine babesiosis is variable in its clinical manifestations, which in turn depend on the particular complications that develop in the course of the disease. Commonly reported complications of canine babesiosis are: acute renal failure, cerebral babesiosis, coagulopathy, icterus and hepatopathy, immune-mediated hemolytic anemia (IMHA), acute respiratory distress syndrome (ARDS), hemoconcentration, shock, and multiple organ dysfunction syndrome (MODS) (MATIJATKO et al., 2005;MATIJATKO et al., 2010;KOSTER et al., 2015). > The many and varied clinical manifestations of canine babesiosis cannot be linked to an organism that is restricted solely to erythrocytes.

[7] Bovine Babesiosis in Turkey: Impact, Current Gaps, and Opportunities for Intervention

• Authors: S. Ozubek, R. Bastos, Heba F. Alzan, A. Inci, M. Aktas et al.
• Year: 2020
• Venue: Pathogens
• URL: https://www.semanticscholar.org/paper/960a224aec3b5038c44ef0c2b6106d4bd6db434c
• DOI: 10.3390/pathogens9121041
• PMID: 33322637
• PMCID: 7763958
• Citations: 46
• Influential citations: 3
• Summary: Development of state-of-the-art research programs in bovine babesiosis to address current gaps in knowledge and implementation of long-term plans to control the disease will surely result in important economic, nutritional, and public health benefits for the country and the region.
• Evidence snippets:
• Snippet 1 (score: 0.364) > Two characteristics that define sensu stricto Babesia parasites are their ability to be transmitted transovarially by tick vectors and exclusively infect red blood cells (RBC) in their vertebrate host. These aspects are particularly important for B. bovis, B. bigemina, and B. divergens, the major causative agents of bovine babesiosis [6,7]. > Growth of asexual stages of Babesia parasites inside the vertebrate host RBC causes severe intravascular hemolytic anemia, which is a pathognomonic sign of the acute disease and highly debilitating for the host. Additionally, fever, prostration, abortion, and temporary infertility are also common clinical findings during acute infection. Hemoglobinuria is also usually present at the peak of the hemolytic crisis in B. bigemina or B. divergens infection and in late stages of the disease caused by B. bovis. In addition, residues and toxic metabolites released as a result of the infection and RBC destruction can negatively affect host organ systems [6][7][8]. Moreover, B. bovis has the unique ability to evade the cattle immune system by expressing proteins that facilitate cytoadhesion of infected RBC to capillaries, such as in the brain, causing neurological symptoms and generalized organ failure, a feature that results in increased virulence. Altogether, these pathological mechanisms frequently lead to rapid death of cattle during the acute stage of the disease, especially when affecting adult naïve animals. > Upon infection, the immune system of the host responds differentially, depending on the age of the animals. While young animals, less than seven months old, are frequently able to control severe acute babesiosis and can survive re-exposures to the parasites, older than one-year-old animals often succumb rapidly to infection. Features associated with resistance in young animals include early and strong activation of the innate and adaptive immune effectors. Briefly, the parasite expresses molecules able to bind pathogen associated molecular patterns (PAMPs) receptors expressed on the surface of dendritic cells (DC), macrophages, neutrophils, and monocytes, especially TLR9 [9,10], and an immune response is initiated.

[8] LC-MS/MS analysis of the dog serum phosphoproteome reveals novel and conserved phosphorylation sites: Phosphoprotein patterns in babesiosis caused by Babesia canis, a case study

• Authors: A. Galán, A. Horvatić, J. Kuleš, Petra Bilić, Jelena Gotić et al.
• Year: 2018
• Venue: PLoS ONE
• URL: https://www.semanticscholar.org/paper/04c4f2552dde9f329a0d7046a9ebb394ece93c90
• DOI: 10.1371/journal.pone.0207245
• PMID: 30485286
• PMCID: 6261647
• Citations: 14
• Summary: The alterations of phosphorylated proteins observed in canine babesiosis caused by Babesia canis suggest new insights into the largely neglected role of extracellular protein phosphorylation in health and disease, encouraging urgent further research on this area.
• Evidence snippets:
• Snippet 1 (score: 0.351) > [33,34]. Cytokines have also been suggested as markers associated to the occurrence of complications in canine babesiosis elicited by several babesial species [35,36]. > Interestingly, a polymorphic membrane phosphoprotein (BrEMA1) has been described on the plasma membrane of Babesia Rossi-infected erythrocytes that is suspected to constitute a major virulence factor [37]. Babesia canis-caused infection could potentially contribute with the parasite's phosphoproteins to the canine serum proteome, acting as biomarkers of the infection. Some other phosphoproteins such as Trypanosoma cruzi's calcineurin B, a phosphatase, are involved in host cell invasion [38] and ecto-kinases have been found to be secreted by Leishmania major [39]. Moreover, phosphorylation of extracellular proteins can operate in signaling pathways responsible for cellular adaptation [5,6], making serum an untapped source of phosphoproteins suitable for better understanding disease pathophysiology and discovery of disease biomarkers [28]. > The present study shows an approach to characterize qualitatively individual serum samples and quantitatively pools containing the same 10 control samples and 10 samples from dogs suffering from babesiosis before the onset of organic dysfunction [40]. In order to test alterations in serum phosphoproteins as potential markers for babesiosis, we have used state-ofthe-art phosphopeptide enrichment procedures and optimized LC-MS/MS protocols to maximize the detection of phosphorylation sites. Combined qualitative and quantitative analyses offer novel data on the alteration of phosphoprotein levels in babesiosis, a hemolytic infection closely related to malaria and sepsis and the concomitant acute systemic inflammation. Variations observed could represent candidate biomarkers for the early detection of babesiosis in dogs and show potential usefulness in clinical applications.

[9] Differential Regulation of Interferon Signaling Pathways in CD4+ T Cells of the Low Type-2 Obesity-Associated Asthma Phenotype

• Authors: Fahd Alhamdan, L. Marsh, F. Pedersen, B. A. Alhamwe, C. Thölken et al.
• Year: 2021
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/64e368bc44d989aa672152b1812fa77c44e3189c
• DOI: 10.3390/ijms221810144
• PMID: 34576307
• PMCID: 8469911
• Citations: 23
• Summary: The specific activation of interferon (IFN)-stimulated genes associated with IFN-related signaling and viral infection pathways might provide a novel view of the molecular mechanisms associated with the development of the low type-2 obesity-associated asthma phenotype, which is a step ahead in theDevelopment of new stratified therapeutic approaches.
• Evidence snippets:
• Snippet 1 (score: 0.343) > Over the last decades, non-communicable diseases (NCDs) have become the major cause of death worldwide, especially after the development of effective anti-infectious measures of prevention (vaccines) and treatment (antibiotics) [1][2][3]. Moreover, they represent a huge burden on the healthcare system and economic situation [4,5]. Prevalence and incidence of NCDs are still further increasing along with ongoing urbanization, industrialization, and globalization of unhealthy diet and lifestyles [6,7]. According to the World Health Organization (WHO), the rapid increase in the NCDs is mainly driven by various risk factors including tobacco, harmful use of alcohol, and obesity [8]. Furthermore, different NCDs and their major risk factors seem to have substantially overlapping underlying mechanisms, often involving immunometabolic alterations [9,10]. Combinations of certain NCDs and associated risk factors can create separate specific disease entities, classified as a clinical subtype or phenotype [11]. > Obesity is a key risk factor underlying a variety of major NCDs, including asthma [10,12]. The comorbidity of obesity and asthma is referred to as obesity-associated asthma [13,14]. Various associated clinical characteristics of obesity and asthma have been described. The major obesity-associated asthma phenotype is characterized as "late-onset, severe and difficult to treat, type-2 low inflammation disease and presenting mostly in women" [15][16][17]. While these detailed clinical characteristics strictly define this particular phenotype of asthma, the specific underlying cellular and molecular mechanisms of this phenotype are still only poorly understood. > Gene expression alterations, especially in cells critically involved in disease development, represent a major molecular contributor to the pathophysiology of chronic inflammatory diseases such as asthma. Subsets of CD4 + T cells, such as Th1, Th2, and Th17 have been shown to differentially contribute to the initiation and perpetuation of specific asthma phenotypes [18,19]. Certain biological pathways and cellular processes play an essential role in the polarization of the CD4 + T cells subtypes [20].

[10] The evolving burden of asthma and contemporary advances in management: Implications for clinical practice in Southern Africa

• Authors: A. Kiboneka
• Year: 2020
• Venue: Unknown venue
• URL: https://www.semanticscholar.org/paper/0ba536bc7dbea898dcaabe247c92c7897c7e059c
• DOI: 10.30574/wjarr.2020.8.3.0315
• Citations: 1
• Summary: The development of novel asthma phenotyping & endo typing plus better classification of patients using machine learning and big data have markedly improved asthma treatment outcomes in both children and Adults, and several research groups have developed cluster analyses of phenotypes in severe asthma.
• Evidence snippets:
• Snippet 1 (score: 0.343) > Research Program (SARP) I and II cohorts to study mechanisms differentiating severe from non-severe asthma. SARP investigators characterized severe asthma as a heterogeneous syndrome with diverse molecular, biochemical, and cellular inflammatory features and structure-function abnormalities. > Adults and children with severe asthma were further categorized by unbiased statistical methods into clusters based on distinguishing clinical features. These studies have not been done in Sub-Sahara Africa. Research performed over the past one to two decades has sought to better understand the heterogeneous clinical nature of asthma. Whereas older attempts at phenotyping asthma emphasized the duality of allergic vs. non-allergic asthma, more recent non-biased analyses have attempted to cluster patients by a multitude of possible features, including age of onset, atopy, severity of airways obstruction, and requirement for medication. Examples of these phenotypes include early-onset mild allergic asthma, later-onset asthma associated with obesity, and severe non-atopic asthma with frequent exacerbations. The elucidation of asthma phenotypes has been further refined by including information regarding pathophysiologic mechanisms present in different groups. These groups, called endo-types, include examples such as aspirin-exacerbated respiratory disease and allergic bronchopulmonary mycosis. > A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different patho-genetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term 'endotype'. > Classification of asthma based on endo-types provides advantages for epidemiological, genetic, and drug-related studies. A successful definition of endo-types should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic-mechanism underlying phenotypes or subgroups within a phenotype is important. > The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care.

[11] Solving the Evidence Interpretability Crisis in Health Technology Assessment: A Role for Mechanistic Models?

• Authors: E. Courcelles, J. Boissel, J. Massol, I. Klingmann, R. Kahoul et al.
• Year: 2022
• Venue: Frontiers in Medical Technology
• URL: https://www.semanticscholar.org/paper/877d5b1b75599745f704a9c8371f74601ff17e2f
• DOI: 10.3389/fmedt.2022.810315
• PMID: 35281671
• PMCID: 8907708
• Citations: 6
• Summary: Light is shed on different stakeholder's contributions and needs in the appraisal phase and how mechanistic modeling strategies and reporting can contribute to this effort to implement mechanistic models central in the evidence generation, synthesis, and appraisal of HTA so that the totality of mechanistic and clinical evidence can be leveraged by all relevant stakeholders.
• Evidence snippets:
• Snippet 1 (score: 0.337) > A second limitation in HTA is the fact that currently population (and sometimes stratified) medicine is pursued during clinical Uncertainty not completely addressed in competent authority assessment report Example use of MIDD relevant to address uncertainty potentially also during HTA What is the optimal dosage in the clinical context? > Physiologically based pharmacokinetic models can investigate dosing-regimens relevant for regulatory review and product labels (9) and can also mimic real-life adherence to prescribed treatment regimens (see also below) or pharmacology-relevant characteristics of special populations as well as drug-drug interactions. > What is the duration of the effectiveness, especially with chronic use of a treatment? > Mechanistic models can predict the long-term disease progression by extrapolation of shorter-term findings under the constraints of how the components of the system function (and these constraints convey biological plausibility by design). An example is the use of a mechanism-based disease progression model for comparison of long-term effects of pioglitazone, metformin, and gliclazide on disease processes underlying Type 2 Diabetes Mellitus (10). Another example is prediction of long-term outcomes by short-term marker data as demonstrated by a semi-mechanistic approach in context of osteoporosis treatment (11). > What is the efficacy for relevant clinical outcomes? > Mechanistic models combined with pharmacometric approaches can translate findings for one outcome to a range of other outcomes. An example of survival modeling on the back of a mechanistic description is the modeling framework for CD19-Specific CAR-T cell immunotherapy using a quantitative systems pharmacology model (12). > What is the size of the clinical effect dependent on patient characteristics and extrinsic factors? > Data-driven modeling techniques can capture correlation within clinical data. Describing the clinical effect of a drug can also be based on mechanistic considerations. Such models either (a) link disease phenotypes to increasingly granular mathematical representations of pathophysiologic processes (top-down approach) or (b) derive functional, computable cellular networks from the molecular building blocks of genes and proteins to elucidate the impact of pathologic or therapeutic alterations on network operating states and hence clinical phenotype (bottom-up) [

[12] Changes in Serum Proteomic Profiles at Different Stages of Pregnancy Toxemia in Goats

• Authors: M. Uzti̇mür, C. N. Ünal, Gurler Akpinar
• Year: 2025
• Venue: Journal of Veterinary Internal Medicine
• URL: https://www.semanticscholar.org/paper/4b9c488b5dbd65d7b26fd2ad9aed70e8c4b59942
• DOI: 10.1111/jvim.70139
• PMID: 40492724
• PMCID: 12150350
• Summary: Understanding the serum proteome profiles of goats with pregnancy toxemia might help identify the proteomes and pathways responsible for the development of this disease and improve diagnosis and treatment.
• Evidence snippets:
• Snippet 1 (score: 0.336) > The pathophysiology and progression of this disease are not fully understood. > Traditional biomedical research has focused on the analysis of single genes, proteins, metabolites, or metabolic pathways in diseases. This molecular reductionist approach is based on the assumption that identifying genetic variations and molecular components will lead to new treatments for diseases [13][14][15][16]. However, many diseases are complex and multifactorial, and in order to determine the phenotype of such diseases, it is necessary to understand the changes that occur in more than one gene, pathway, protein, or metabolite at the cellular, tissue, and organismal levels [17][18][19]. Therefore, in recent years, proteomics, as one field of multi-omics technologies, has helped in evaluating the complex pathogenetic mechanisms of different diseases from a broad perspective and has made substantial contributions [20,21]. In veterinary medicine, proteomic analysis of metabolic diseases such as ketosis [16], hypocalcemia [22], and fatty liver [23] in dairy cows has contributed valuable insights for the definition of new pathophysiological pathways and new diagnosis and treatment protocols for these diseases. The proteomic approach can contribute importantly to a broad and detailed understanding of the changes that occur at the organismal level associated with the increase in BHBA concentration in goats with pregnancy toxemia. Our aim was to evaluate the serum protein profiles of goats with SPT or CPT using proteomic techniques to determine the proteomic profiles of these animals and to identify the relevant pathophysiological mechanisms.

[13] 18O-assisted dynamic metabolomics for individualized diagnostics and treatment of human diseases

• Authors: E. Nemutlu, Song Zhang, N. Juranic, A. Terzic, S. Macura et al.
• Year: 2012
• Venue: Croatian Medical Journal
• URL: https://www.semanticscholar.org/paper/880f053c7f060db4b990e447d0a22c4b69372ddb
• DOI: 10.3325/cmj.2012.53.529
• PMID: 23275318
• PMCID: 3541579
• Citations: 28
• Summary: The potential use of dynamic phosphometabolomic platform for disease diagnostics currently under development at Mayo Clinic is described and discussed briefly.
• Evidence snippets:
• Snippet 1 (score: 0.336) > Living cells represent an integrated and interacting network of genes, transcripts, proteins, small signaling molecules, and metabolites that define cellular phenotype and function. Traditionally the focus of biomedical research was on individual genes, single protein targets, single metabolites, and metabolic or signaling pathways. This "molecular reductionist" paradigm was based on the assumption that identifying genetic variations and molecular components would lead to discovery of cures for human diseases. However, most of diseases are complex and multi-factorial and the disease phenotype is determined by the alterations of multiple genes, pathways, proteins and metabolites (at cellular, tissue, and organismal levels). Therefore, an integrated "omics" approach is more viable direction for uncovering alterations in metabolic networks, disease mechanisms, and mechanisms of drug effects. > Recent advent of large-scale metabolomics and fluxomic (metabolite dynamics and metabolic flux analysis) completed the "omics revolution" (Figure 1), where genomics, transcriptomics, proteomics, metabolomics, and fluxomics all together complement phenotype determination of living organism. Such integrated "omics" cascades provide a framework for advances in system and network biology, integrative physiology, and system medicine as well as system pharmacology and regenerative medicine. Noteworthy is the "reverse omic" approach or "metabolomicsinformed pharmacogenomics, " where discovery of specific metabolite changes have led to discovery of genetic alterations (2). Therefore, bringing new "omics" technologies to clinical practice will improve disease diagnostics and treatment by targeting drugs and procedures for each unique transcriptomic and metabolomic profiles.

[14] Chemotherapy and Mechanisms of Resistance in Breast Cancer

• Authors: A. Oliveira, R. E. Santos, F. F. O. Rodrigues
• Year: 2012
• Venue: Unknown venue
• URL: https://www.semanticscholar.org/paper/502a86d8bcd7208be6f539fcceba631f82f25a7d
• DOI: 10.5772/24629
• Summary: The addition of adjuvant polychemotherapy in advanced breast cancer showed gain by controlling survival of micrometastases in patients with lymph nodes affected by cancer or not.
• Evidence snippets:
• Snippet 1 (score: 0.334) > The main reasons responsible for treatment failure in cancer patients are the mechanisms of drug resistance and emergence of disseminated disease (Terek et al, 2003). We identified two types of resistance most relevant to BC: primary resistance, which corresponds to the clinical situation where the patient showed no response to therapy, and secondary or acquired resistance in which, initially, there is an observed response and a subsequent failure of the treatment regimen (Kroger et al, 1999). Several mechanisms may cause the phenotype of multidrug resistance to chemotherapy drugs and are well characterized in in vitro experiments, including alterations in systemic pharmacology (pharmacokinetics and metabolism), extracellular mechanisms (tumor environment, multicellular drug resistance), and cellular mechanisms (cellular pharmacology, activation and inactivation of drugs, modification of specific targets and regulatory pathways of apoptosis) (Leonessa et al, 2003, Riddick et al, 2005. Identification of factors that affect cell metabolism, which are related to drug resistance, will enable the identification of which patients are at particular risk of treatment failure. Among the biochemical and molecular mechanisms of drug resistance, we stress: changes in the activity of topoisomerase II, alterations in the DNA repair mechanism, overexpression of P-glycoprotein; high intracellular concentrations of enzymes purification of cellular metabolism -among them enzymes the family of glutathione S-transferases (GSTs) and changes in the mechanisms of signaling via c-Jun N-terminal kinase 1 (JNK1) -and "apoptosis signal-regulating kinase (ASK1) required for activation of the" mitogenactivated protein (MAP kinases) in apoptosis and cellular restoration. These pathways are also mediated by proteins encoded by genes of GSTs (O'Brien, Tew, 1996;Burg, Mulder, 2002, L'Ecuyer et al, 2004). Different response rates to particular chemotherapy regimens, as observed in patient groups with the same biological characteristics and stage, suggest the existence of different mechanisms of drug resistance, probably induced by genetic alterations (Hayes, Pulford, 1995;O'Brien , Tew, 1996;Pakunlu et al, 2003). Among the mechanisms of purification of cellular metabolism involved in the

[15] Organoids in gastrointestinal diseases: from bench to clinic

• Authors: Qinying Wang, Fanying Guo, Qinyuan Zhang, Tingting Hu, Yutao Jin et al.
• Year: 2024
• Venue: MedComm
• URL: https://www.semanticscholar.org/paper/9b8880d8b9d45670da950197d7e353794f51d09e
• DOI: 10.1002/mco2.574
• PMID: 38948115
• PMCID: 11214594
• Citations: 12
• Summary: A comprehensive and systematical depiction of organoids models is drawn, providing a novel insight into the utilization of organoids models from bench to clinic and clinical adhibition.
• Evidence snippets:
• Snippet 1 (score: 0.333) > Organoids models offer a robust platform for investigating the potential mechanisms of GI diseases and evaluating potential therapeutic interventions.By culturing organoids derived from patients' tissues or stem cells, researchers can delve into disease-specific cellular and molecular pathways, encompassing aberrant cell signaling, perturbed immune responses, and dysfunctional metabolic processes.These disease-specific phenotypes enable the study of disease progression, screening of prospective therapeutics, as well as identification of novel drug targets and mechanisms of action for GI diseases in a clinically relevant context.

[16] Immunization of Cattle With Recombinant Structural Ectodomains I and II of Babesia bovis Apical Membrane Antigen 1 [BbAMA-1(I/II)] Induces Strong Th1 Immune Response

• Authors: Amarin Rittipornlertrak, Boondarika Nambooppha, Anucha Muenthaisong, Nisachon Apinda, Pongpisid Koonyosying et al.
• Year: 2022
• Venue: Frontiers in Veterinary Science
• URL: https://www.semanticscholar.org/paper/a1ade815ad596ebd9218b29824de2f1239fdfb8e
• DOI: 10.3389/fvets.2022.917389
• PMID: 35812841
• PMCID: 9260583
• Citations: 3
• Summary: The results indicate that immunization of cattle with BbAMA-1(I/II) could induce strong Th1 cell responses and is recognized as a potential candidate vaccine against B. bovis infection.
• Evidence snippets:
• Snippet 1 (score: 0.332) > Most apicomplexans are obligate intracellular parasites. Babesia, an apicomplexan parasite, is a tick-transmitted hemoprotozooan. The most economically relevant bovine babesias are Babesia bovis (B. bovis) and Babesia bigemina (B. bigemina). Presently, a large number of cattle are at risk of exposure to bovine babesiosis. Bovine babesiosis is recognized as a global disease that has been the cause of significant economic losses to the livestock industry (1). Climate change is one of the factors that can influence the control of bovine babesiosis (2). Pathologically, a cyclical asexual replication of Babesia in red blood cells (RBC) that is associated with an excessive immune response has been known to lead to the development of several clinical manifestations. In general, bovine babesiosis can be treated with chemotherapy (1). However, the emergence of drug resistance in B. bovis has been recently documented (3). Although live attenuated vaccines are available in some endemic countries, the applications for wide use of these vaccines are limited for a number of reasons. At present, there are no safe and effective vaccines that protect cattle against the virulent pathogens (4). Thus, novel vaccines are increasingly desirable and urgently needed to control this disease (2). > The host-parasite interaction is of major importance for parasite survival. Without host cells, which supply environment and nutrition, the parasitic protozoa cannot grow and survive. The formation of a moving junction (MJ) between the parasite and host cell membranes is an important conserved mechanism that facilitates the parasitic invasion into host cells during the asexual growth cycle of apicomplexan parasites (5). The apical membrane antigen 1 (AMA-1) has been well characterized and reported to be involved in MJ formation in coordination with the rhoptry neck 2 (RON2) protein in Toxoplasma and Plasmodium (6,7). It is likely directly responsible for reorientation and initiates the junctional contact. AMA-1, a microneme protein (MIC), is a type I integral membrane protein that is composed of three distinct structures (8).

[17] Genomic Study of Babesia bovis Infection Level and Its Association With Tick Count in Hereford and Braford Cattle

• Authors: L. Cavani, C. U. Braz, R. Giglioti, C. Okino, C. C. Gulias-Gomes et al.
• Year: 2020
• Venue: Frontiers in Immunology
• URL: https://www.semanticscholar.org/paper/427b382a8aaac279e7a7739ebba41e6bd62052c0
• DOI: 10.3389/fimmu.2020.01905
• PMID: 33013839
• PMCID: 7493685
• Citations: 10
• Summary: Although the genetic correlation between IB and TC was weak, some candidate genes for IB were also reported in tick infestation studies, and they were also involved in biological resistance processes, suggesting that genomic predictions could be used as a tool to improve genetics for IB, especially if a larger training population is developed.
• Evidence snippets:
• Snippet 1 (score: 0.329) > Figure 2 shows the Manhattan plot with the percentages of additive genetic variance explained by each SNP for the IB trait. The top 10 SNPs (Table 5) explained 5.05% of IB additive genetic variance and identified 42 candidate genes involved in biological mechanisms that may underlie B. bovis resistance in cattle. Defense against parasites is mediated by sequential and coordinated immune responses called innate and adaptative (65), and several of the candidate genes participate in immune system pathways (ATP8A1, LCP1, LRCH1, QSOX1, FGF2, DSC1, DSC3, FGFR2, and CEBPG), which include adaptive and innate immune systems, and cytokine signaling pathways, indicating that genetic variations in these genes can alter the immune response and consequently, influence susceptibility and outcome of babesiosis in cattle. An essential aspect of B. bovis infection is that young calves have strong innate immunity, which lasts until about 6 months of age (66). Animals that survive infection with B. bovis become persistently infected and resistant to the clinical form of the disease, a phenomenon known as concomitant immunity (67). Adaptative immunity mechanisms are responsible for the absence of clinical signs in persistently infected animals. LCP1 is a protein of the plastin family. This family is composed of actin-binding proteins that are conserved evolutionarily and expressed in different types of plants and animals (68). In mammals, three isoforms have been identified: T, I, and L-plastin. This latter group includes LCP1 that is expressed in hematopoietic cell lines, with essential functions in the activation of macrophages (69), lymphocytes, and granulocytes (70). According to Brown (71), the immune response against babesiosis depends on the activation of CD4+ T lymphocytes in the development of acquired protein antigen-specific responses. CD4+ T cells are essential for coordinating high-affinity IgG production and activating macrophages through the production of IFN-È. > LRCH1 also encodes proteins that influence the migration of CD4+ T cells (72).

[18] Targeting Hepatic Stellate Cells for the Prevention and Treatment of Liver Cirrhosis and Hepatocellular Carcinoma: Strategies and Clinical Translation

• Authors: Hao Xiong, Jinsheng Guo
• Year: 2025
• Venue: Pharmaceuticals
• URL: https://www.semanticscholar.org/paper/76e92127053136900f7e3f10e2c9278251ced5d2
• DOI: 10.3390/ph18040507
• PMID: 40283943
• PMCID: 12030350
• Citations: 10
• Summary: HSC-targeted approaches using specific surface markers and receptors may enable the selective delivery of drugs, oligonucleotides, and therapeutic peptides that exert optimized anti-fibrotic and anti-HCC effects.
• Evidence snippets:
• Snippet 1 (score: 0.326) > Significant progress has been made in elucidating the cellular and molecular mechanisms of liver fibrosis; however, only a few findings have been successfully translated into clinical applications. Firstly, the high cost of drug development and target validation necessitates prolonged timelines and substantial financial investment. Secondly, as regulatory requirements become more stringent, there is an increasing demand for drugs with well-defined clinical efficacy and safety profiles. Moreover, the efficacy observed in animal models often fails to fully translate to clinical settings due to differences in pharmacokinetics, extracellular matrix (ECM) cross-linking, and disease pathophysiology. Despite advancements in anti-fibrotic drug development, accurately identifying ideal noninvasive biomarkers for fibrotic activity and establishing consensus on optimal clinical endpoints remain significant challenges [113,114]. > Currently, addressing the underlying cause remains the only proven strategy to halt or reverse liver fibrosis progression, while the development of effective anti-fibrotic therapies continues to pose a major challenge in liver disease management. Over the past few decades, substantial progress has been made in elucidating the cellular and molecular mechanisms underlying liver fibrosis. Liver fibrosis is a complex pathological change involving multiple cells, factors, and pathways, and the study of the cellular and molecular mechanisms of its occurrence and development provides an important theoretical basis and therapeutic target for clinical drug development. It is anticipated that improved animal models and well-designed clinical trials will facilitate the successful translation of anti-fibrotic research into effective clinical treatments in the near future.

[19] New therapeutic targets in rare genetic skeletal diseases

• Authors: M. Briggs, Peter A. Bell, M. Wright, K. A. Pirog
• Year: 2015
• Venue: Expert Opinion on Orphan Drugs
• URL: https://www.semanticscholar.org/paper/1363107f71ae6d2d60abca471cddf3da5d13644b
• DOI: 10.1517/21678707.2015.1083853
• PMID: 26635999
• PMCID: 4643203
• Citations: 38
• Influential citations: 1
• Summary: An overview of disease mechanisms that are shared amongst groups of different GSDs and potential therapeutic approaches that are under investigation are described to generate critical mass for the identification and validation of novel therapeutic targets and biomarkers.
• Evidence snippets:
• Snippet 1 (score: 0.325) > proteins of the cartilage ECM such as type II collagen [50]. However, emerging knowledge suggests that the primary genetic defect may be less important than the cells' response to the expression of the mutant gene product [107]. Moreover, the largely overlooked response of a cell (i.e. chondrocyte) to the abnormal extracellular environment is also important for disease progression as illustrated by several GSDs discussed in this review. > It is important that 'omics'-based approaches and technologies are systematically applied to the study of rare GSDs so that definitive reference profiles and disease signatures are generated for each phenotype. These can then be used in a Systems Biology approach to identify both common and dissimilar pathological signatures and disease mechanisms. This approach is entirely dependent upon relevant in vitro and in vivo models (and also novel 'disease-mechanism phenocopies' [107]) for testing new diagnostic and prognostic tools and for determining the molecular mechanisms that underpin the pathophysiology so that effective therapeutic treatments can be developed and validated. This approach will eventually lead to personalized treatments and care strategies centred on shared disease mechanisms with the use of relevant biomarkers to monitor the efficacy of treatment and disease progression. > It is vital that all relevant stakeholders are involved from the outset in defining the appropriate outcomes of any potential therapeutic regime. The perceptions of a successful therapy can differ widely between the clinical academic community and the relevant patient-support groups and it is vital that there is engagement on all these issues. > In summary, the identification of causative genes and mutations for GSDs over the last 20 years, coupled with the generation and in-depth analysis of a plethora of relevant cell and mouse models, has derived new knowledge on disease mechanisms and suggested potential therapeutic targets. The fast-evolving hypothesis that clinically disparate diseases can share common disease mechanisms is a powerful concept that will generate critical mass for the identification and validation of novel therapeutic targets and biomarkers.

[20] Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

• Authors: H. Breiteneder, Z. Diamant, T. Eiwegger, W. Fokkens, C. Traidl‐Hoffmann et al.
• Year: 2019
• Venue: Allergy
• URL: https://www.semanticscholar.org/paper/e19b0755c4f4903f68377333676edebf9bd73c89
• DOI: 10.1111/all.13851
• PMID: 31056763
• PMCID: 6973012
• Citations: 90
• Influential citations: 3
• Summary: Recent developments in research and patient care and future trends in the discipline are reviewed and topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen‐specific immunotherapy for airway disease are highlighted.
• Evidence snippets:
• Snippet 1 (score: 0.325) > The past decades have witnessed extensive progress in unraveling cellular and molecular mechanisms of immune regulation in asthma, allergic diseases, organ transplantation, autoimmune diseases, tumor biology, and chronic infections. 1,2 Consequently, a better understanding of the functions, the reciprocal regulation, and the counterbalance of subsets of immune and inflammatory cells but also structural cells-for example, epithelial and vascular cells, airway smooth muscle cells, neuroendocrine system-that interact via various intercellular messengers will indicate avenues for immune interventions and novel treatment modalities of allergic diseases and immunological disorders. It is generally expected that drug development in the next decades will show a significant shift from chemicals to biologicals. > After more than 20 years without any breakthrough drug becoming available for patients, several disciplines including allergology are now experiencing extraordinary times with the recent licensing of several major biological drugs and novel allergen-specific immunotherapy (AIT) vaccines. Several biological modifiers of the immune response targeting intracellular messengers or their receptors have been developed to date. [3][4][5][6][7][8] In addition, a number of promising small molecule drugs and vaccines are in the development pipeline. [9][10][11] This new era is now calling for the development of biomarkers and phenoand endotyping of diseases for customized patient care, which is termed stratified medicine, precision medicine, or personalized medicine. 4 Distinguishing phenotypes of a complex disease covers the observable clinically relevant properties of the disease but does not show a direct relationship to disease etiology and pathophysiology. In a complex condition, such as asthma, different pathogenetic mechanisms can induce similar clinical manifestations; however, they may require different treatment approaches. 12,13 These pathophysiological mechanisms underlying disease subgroups are addressed by the term "endotype." [12][13][14] Classification of complex diseases based on the concept of endotypes provides advantages for epidemiological, genetic, and drug-related studies. Accurate endotyping by using reliable biomarkers reflects the natural history of the disease and aims to predict the response to (targeted) treatments. 15 Recent studies have focused on better understanding

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.