Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Oroya fever. Core disease mechanisms, molecular and cellular pathways, inv...

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

• Papers retrieved: 20
• Snippets retrieved: 20

Relevant Papers

[1] 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: 0.405) > , 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

[2] Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

• Authors: W. Tulalamba, T. Janvilisri
• Year: 2012
• Venue: International Journal of Cell Biology
• URL: https://www.semanticscholar.org/paper/307cb9186444d9dad6e2e3b53763be0de76de186
• DOI: 10.1155/2012/594681
• PMID: 22500174
• PMCID: 3303613
• Citations: 93
• Influential citations: 5
• Summary: The molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression and the important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.
• Evidence snippets:
• Snippet 1 (score: 0.365) > In the pregenomic eras, highly integrated and complex circuitry of molecular signaling in NPC pathogenesis was only partially understood. Over the past decade, the knowledge of the molecular mechanisms in NPC carcinogenesis has been rapidly accumulated. Dysregulation and abnormal protein expression of molecules in certain signaling pathways involved in cellular functions including proliferation, adhesion, survival, and apoptosis has been demonstrated in the NPC cells. Detailed information on the complex network in signaling pathway leading to a coordinated pattern of gene expression and regulation in NPC will undoubtedly provide important clues to develop novel prognostic and therapeutic strategies for this cancer. Refining molecular markers into clinically relevant assays may assist in the detection of NPC in asymptomatic patients, as well as stage classification and monitoring disease progression and treatments. Furthermore, selective regulation of particular proteins targeting cancer cell proliferation, invasion, and apoptosis is a hopeful prospect for future anticancer therapy that slow disease progression and improve survival.

[3] 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: 0.355) > 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.

[4] Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction

• Authors: Yi Liu, Yang Zhang, Huan Wei, Li Wang, Lishang Liao
• Year: 2025
• Venue: Scientific Reports
• URL: https://www.semanticscholar.org/paper/19a91d9c8cabec6a5a186729d545077e252ecb67
• DOI: 10.1038/s41598-025-97642-8
• PMID: 40229542
• PMCID: 11997208
• Summary: The findings not only elucidate the molecular mechanisms underlying SAH but also provide robust bioinformatics and experimental evidence supporting IRN as a promising therapeutic candidate, offering novel insights for future intervention strategies in SAH.
• Evidence snippets:
• Snippet 1 (score: 0.354) > involved in SAH pathology. As a result, our understanding of the cellular composition and microenvironment in SAH remains incomplete 8 . > Advances in bioinformatics provide powerful tools to analyze large-scale gene expression data and understand complex biological processes. By integrating transcriptomic data with immune cell infiltration analysis, we can gain a deeper understanding of the molecular mechanisms underlying SAH and identify potential key genes as therapeutic targets 9,10 . Previous studies have indicated that inflammation, oxidative stress, and cell death play crucial roles in the development of SAH, processes that are often closely associated with changes in specific cell types and immune responses 11 . > The goal of this study is to explore the molecular mechanisms of SAH, with a focus on immune cell infiltration and its role in disease progression. We aim to identify key genes and signaling pathways associated with SAH and investigate potential therapeutic strategies. Specifically, we will examine Isorhynchophylline (IRN) as a potential treatment for SAH and analyze its effects on relevant targets and signaling pathways. Through a comprehensive understanding of the pathological features of SAH, this study aims to provide valuable insights into future clinical interventions and treatment strategies.

[5] Multi-omics approach to COVID-19: a domain-based literature review

• Authors: C. Montaldo, F. Messina, I. Abbate, M. Antonioli, V. Bordoni et al.
• Year: 2021
• Venue: Journal of Translational Medicine
• URL: https://www.semanticscholar.org/paper/0c7804617654881ff5b118da3e412f1a4b3339c4
• DOI: 10.1186/s12967-021-03168-8
• PMID: 34876157
• PMCID: 8649311
• Citations: 17
• Influential citations: 1
• Summary: The analysis revealed that dysregulated pathways of innate immune responses can affect COVID-19 progression and outcomes, and multi-omics approach may help to further investigate unknown aspects of the disease.
• Evidence snippets:
• Snippet 1 (score: 0.353) > Omics data, driven by rapid advances in laboratory techniques, have been generated very quickly during the COVID-19 pandemic. Our aim is to use omics data to highlight the involvement of specific pathways, as well as that of cell types and organs, in the pathophysiology of COVID-19, and to highlight their links with clinical phenotypes of SARS-CoV-2 infection. The analysis was based on the domain model, where for domain it is intended a conceptual repository, useful to summarize multiple biological pathways involved at different levels. The relevant domains considered in the analysis were: virus, pathways and phenotypes. An interdisciplinary expert working group was defined for each domain, to carry out an independent literature scoping review. The analysis revealed that dysregulated pathways of innate immune responses, (i.e., complement activation, inflammatory responses, neutrophil activation and degranulation, platelet degranulation) can affect COVID-19 progression and outcomes. These results are consistent with several clinical studies. Multi-omics approach may help to further investigate unknown aspects of the disease. However, the disease mechanisms are too complex to be explained by a single molecular signature and it is necessary to consider an integrated approach to identify hallmarks of severity.

[6] Role of Transcriptomics in Precision Oncology

• Authors: Ruby Srivastava
• Year: 2024
• Venue: Reports of Radiotherapy and Oncology
• URL: https://www.semanticscholar.org/paper/0bd862558bbb7286336111d9dfd232b5f905d3d9
• DOI: 10.5812/rro-142195
• Citations: 4
• Summary: : Transcriptome profiling is one of the most widely used approaches in the field of multiomics research. It plays a crucial role in the prognostic, diagnostic, and predictive treatment of cancer patients. Novel next-generation sequencing (NGS) technologies permit the identification of cancer biomarkers, gene signatures, and their abnormal expression, affecting oncogenic and molecular targets and novel biomarkers for cancer therapies. Multiomics studies have changed the overall understanding o...
• Evidence snippets:
• Snippet 1 (score: 0.348) > : Transcriptome profiling is one of the most widely used approaches in the field of multiomics research. It plays a crucial role in the prognostic, diagnostic, and predictive treatment of cancer patients. Novel next-generation sequencing (NGS) technologies permit the identification of cancer biomarkers, gene signatures, and their abnormal expression, affecting oncogenic and molecular targets and novel biomarkers for cancer therapies. Multiomics studies have changed the overall understanding of cancer and opened a precise perspective for tumor diagnostics and therapy. The use of these approaches has strengthened our understanding of disease pathophysiology and classifications at the molecular level, including specific interference with drug mechanisms of action. Still, it has limited added value in the clinical setting. The omics data on precision medicine include the application of data from genes, transcripts, and proteins for diagnosis, monitoring of diseases, risk factor determination, counseling, and development of novel therapeutics. Bioinformatics applications have expanded statistics-based analysis toward deriving molecular pathways and process models for characterizing phenotypes and drug action mechanisms. In this review, we will discuss transcriptomics and interference analysis that allows the identification of predictive biomarkers at the molecular level to test drug response and analyze the molecular process interface of disease progression-relevant pathophysiology and mechanism of action to propose predictive biomarkers.

[7] Heat Shock Proteins in Oxidative Stress and Ischemia/Reperfusion Injury and Benefits from Physical Exercises: A Review to the Current Knowledge

• Authors: Jakub Szyller, I. Bil-Lula
• Year: 2021
• Venue: Oxidative Medicine and Cellular Longevity
• URL: https://www.semanticscholar.org/paper/4ec4bee9f1b89cdf5a3c513d847990f3cfc18bb8
• DOI: 10.1155/2021/6678457
• PMID: 33603951
• PMCID: 7868165
• Citations: 114
• Influential citations: 2
• Summary: The latest research focuses on determining the role of H SPs in OS, their antioxidant activity, and the possibility of using HSPs in the treatment of I/R consequences, where reactive oxygen species play a major role.
• Evidence snippets:
• Snippet 1 (score: 0.342) > Heat shock proteins play a cytoprotective role under pathological conditions such as cardiovascular diseases. The knowledge about cellular and molecular mechanisms underlying ROS-mediated modulation of HSP expression can help to better understand the pathophysiology of OS, which is associated with the development of many diseases (cardiovascular, neurodegenerative, etc.). I/R injury is considered a major contributor to tissue damage in multiple clinical situations such as myocardial infarction, stroke, and organ transplantation. Oxidative damage is a key factor in the initiation of I/R. HSP expression is highly sensitive to I/R injury. > Understanding the exact mechanisms of HSP and the structure of the protein interaction network can help to better understand the pathophysiology and treatment of many diseases, as well as to develop new drugs. There is a need to understand the relationship between cell pathways-signaling, metabolism, etc. The relationships between HSP and OS discussed in this work seem to be very complicated and not yet fully understood. Data showed that modulation of HSP expression in reperfusion injuries may result in better treatment of myocardial infarction. This can also help to prepare organs for the transplantation.

[8] Recent Evidences of Epigenetic Alterations in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review

• Authors: R. Ragusa, P. Bufano, A. Tognetti, M. Laurino, Chiara Caselli
• Year: 2025
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/2660cdbbe1f205c631fe890e5c6a3c8d9b81ce5f
• DOI: 10.3390/ijms26062571
• PMID: 40141213
• PMCID: 11942187
• Citations: 6
• Summary: A systematic review of the latest knowledge on epigenetic modifications that characterize COPD, summarizing epigenetic factors that could serve as potential novel biomarkers and therapeutic targets for the treatment of COPD patients.
• Evidence snippets:
• Snippet 1 (score: 0.336) > The papers included were clustered according to epigenetic mechanisms involved in COPD (molecular and cellular processes, as biomarker or therapeutic target). Tables 4-9 describe the extracted information, including the following: Study = name of first author et al., year; Country (Region) = where the study took place; Number of participants = sample size; Type of sample = biological sample employed; Gene affected = gene or group of genes whose expression can be "regulated" by epigenetic mechanisms; Epigenetic alteration = type of epigenetic alteration observed in the presence of disease; Activity in COPD = involvement of epigenetic elements in different molecular and cellular mechanisms associated with COPD; and Role of epigenetic mechanisms = epigenetic modifications that can be used to explain the pathophysiology of COPD or as biomarkers and therapeutic targets.

[9] 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: 0.334) > 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.

[10] From molecular signatures to predictive biomarkers: modeling disease pathophysiology and drug mechanism of action

• Authors: A. Heinzel, P. Perco, G. Mayer, R. Oberbauer, A. Lukas et al.
• Year: 2014
• Venue: Frontiers in Cell and Developmental Biology
• URL: https://www.semanticscholar.org/paper/36d6c03a528c1358c0ae5b667cca5ce73b2fbee5
• DOI: 10.3389/fcell.2014.00037
• PMID: 25364744
• PMCID: 4207010
• Citations: 24
• Summary: This work exemplifies a computational workflow for expanding from statistics-based association analysis toward deriving molecular pathway and process models for characterizing phenotypes and drug mechanism of action, in turn providing precision medicine hypotheses utilizing predictive biomarkers.
• Evidence snippets:
• Snippet 1 (score: 0.333) > In such scenario a biomarker needs to serve as proxy of key mechanistic factors characterizing and driving a disease on a patient-specific level, combined with educating on the specific interference of disease mechanism with drug mechanism of action. For capturing these constraints a detailed molecular map of a clinical phenotype and its interference with a drug mechanism of action is needed, and here integration of Omics profiling adds to identifying such mechanisms (Fechete et al., 2011;Mühlberger et al., 2012). > An a priori stratification of patients based on an appropriately chosen biomarker panel reflecting the pathophysiology of a given patient (group) allowing to determine a match with a specific drug's mechanism of action appears as promising approach. As recently discussed by Himmelfarb et al. fresh approaches are critical in finding therapies to kidney disease benefiting patients, outlining the importance of improving the translational aspect in clinical research (Himmelfarb and Tuttle, 2013). Here, omics technologies have added significantly to the data landscape characterizing chronic kidney disease, however, in a first instance mainly expanding the candidate set of apparently relevant processes and pathways, going in hand with a large number of biomarker candidates, which individually hamper clinically relevant assessment on disease progression (Fechete et al., 2011;Hellemons et al., 2012). > Integrative approaches in the realm of Systems Biology have been proposed for reaching a consensus description of chronic kidney disease pathophysiology, including molecular models of DN as well as of the reno-cardial axis (He et al., 2012;Komorowsky et al., 2012;Mayer et al., 2012;Heinzel et al., 2013). Still, a translation process needs to be followed, joining disease pathophysiology, stratification markers allowing enrichment strategies, combined with on a molecular mechanistic level matching drugs for allowing precision medicine (Mirnezami et al., 2012). In this work we exemplify such procedure on DN being the major clinical presentation leading to end stage renal disease.

[11] 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: 0.331) > 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.

[12] 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: 0.331) > 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.

[13] Recent advances in modelling of cerebellar ataxia using induced pluripotent stem cells

• Authors: M. M. Wong, L. Watson, Esther B. E. Becker
• Year: 2017
• Venue: Journal of neurology & neuromedicine
• URL: https://www.semanticscholar.org/paper/0d962652305116e383ab260b9e82d3a5ffe1722f
• DOI: 10.29245/2572.942X/2017/7.1134
• PMID: 28825058
• PMCID: 5558869
• Citations: 10
• Summary: This review focuses on recent breakthroughs in generating human iPSC-derived Purkinje cells and highlights the future challenges that will need to be addressed in order to fully exploit these models for the modelling of the molecular mechanisms underlying cerebellar ataxias and the development of effective therapeutics.
• Evidence snippets:
• Snippet 1 (score: 0.329) > dominant polyglutamine spinocerebellar ataxias (SCAs) are the most studied forms of ataxias. Despite significant clinical and genetic heterogeneity, emerging evidence points to the existence of common pathogenic mechanisms that may be shared by several genetically distinct forms of cerebellar ataxias (reviewed in5-8). However, it is still unclear how the proposed pathological pathways ultimately result in cerebellar dysfunction and degeneration, predominantly affecting Purkinje cells. > Understanding disease mechanisms is key to treating neurodegenerative disorders. The heterogeneous nature of the cerebellar ataxias combined with the unavailability of human brain tissue and the lack of reliable disease models have, however, hampered our understanding of the molecular disease mechanisms underlying cerebellar ataxias and thus, the development of effective therapies. Although mouse models of several cerebellar ataxias, including FRDA and SCAs, have provided valuable insights into the pathophysiology of these disorders (reviewed in9), many questions remain about the observed species differences in disease phenotypes and the effectiveness of potential drugs in clinical trials. > To help translate research from animal models into novel treatments for ataxia patients, it is essential to validate findings in the relevant affected human cell types, particularly in cerebellar Purkinje cells. The current obstacles might be overcome by exploiting recently developed human induced pluripotent stem cell (iPSC) technology and neuronal differentiation protocols.

[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: 0.329) > 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] 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: 0.327) > 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

[16] Prioritizing Molecular Biomarkers in Asthma and Respiratory Allergy Using Systems Biology

• Authors: Lucía Cremades-Jimeno, M. D. de Pedro, M. López-Ramos, J. Sastre, P. Mínguez et al.
• Year: 2021
• Venue: Frontiers in Immunology
• URL: https://www.semanticscholar.org/paper/d8ca6e130adec2dfa39545eb1763827d9450e4f5
• DOI: 10.3389/fimmu.2021.640791
• PMID: 33936056
• PMCID: 8081895
• Citations: 13
• Influential citations: 1
• Summary: This study has enabled it to prioritize biomarkers depending on the functionality associated with each disease and with specific molecular motifs, which could improve the definition and usefulness of new molecular biomarkers.
• Evidence snippets:
• Snippet 1 (score: 0.326) > Firstly, the molecular characterization of the three pathophysiological processes of interest (respiratory allergy, allergic asthma, and nonallergic asthma) was performed using the Therapeutic Performance Mapping System (TPMS) technology (Anaxomics Biotech, Barcelona, Catalonia, Spain) (31). Briefly, systems biology generates models that are able to reproduce the behavior of a disease in a patient, thus identifying the key genes, proteins, or metabolites in the development of the disease. A dictionary has been created to translate clinical and medical terms into molecular biology data, effectively linking the molecular and the clinical words. This dictionary, called the Biological Effectors Database (BED), relates biological processes (adverse events of drugs, drug indications, diseases, etc.) with the proteins most closely associated with them. Thus, the dictionary acts as a translator of clinical phenotypes into terms comprehensible for protein networks, and conversely allows for the translation of molecular measures toward clinical outcomes. The BED is structured hierarchically, where the biggest level is the entire disease, which is divided into different pathophysiological molecular motifs, which in turn contain the proteins involved in the development of the disease. The motifs are classified into two levels depending on their respective implication, i.e. causal motifs, which are directly related to the onset or pathophysiology of the condition, and symptomatic (manifestative) motifs, which are a consequence of the disease. > In the present study, respiratory allergy, allergic asthma, and non-allergic asthma have been characterized at the molecular level. Therefore, the analysis of high throughput data by means of TPMS allows for identification of those proteins closely associated with the disease of interest and can provide a mechanistic rationale for their involvement. The effector proteins of the manifestative and causal molecular motifs of these three diseases have been identified through bibliographic review and curate data. Figure 1 summarizes the workflow used for this study.

[17] Investigating the role of NPR1 in dilated cardiomyopathy and its potential as a therapeutic target for glucocorticoid therapy

• Authors: Yaomeng Huang, Tongxin Li, Shichao Gao, Shuyu Li, Xiaoran Zhu et al.
• Year: 2023
• Venue: Frontiers in Pharmacology
• URL: https://www.semanticscholar.org/paper/be229f6f2059faab4c97ec0a04bd055adab9dfe1
• DOI: 10.3389/fphar.2023.1290253
• PMID: 38026943
• PMCID: 10662320
• Citations: 4
• Summary: Natriuretic peptide receptor 1 (NPR1) was identified as a core gene associated with DCM through bioinformatics analysis and led to substantial improvements in cardiac and renal function, accompanied by an upregulation of NPR1 expression.
• Evidence snippets:
• Snippet 1 (score: 0.326) > Multiple pathways and molecules are involved in this process; however, the detailed underlying mechanisms remain unclear. In recent years, with the development of high-throughput sequencing and gene chip technologies, the use of bioinformatics technology to explore the occurrence, development, and prognosis of diseases has become a hot topic for scholars worldwide (Hwang et al., 2018;Nayor et al., 2019;Rinschen et al., 2019;Sturm et al., 2019;Montaner et al., 2020). > The present study aimed to use bioinformatics technology to screen for DCM-related genes and investigate their mechanisms, with the purpose of revealing the pathogenesis of DCM and seeking treatment methods. The GSE3586 dataset, containing expression profiles related to DCM, was selected from the Gene Expression Omnibus (GEO) database. This study aimed to predict the core genes that may play crucial roles in disease progression at the molecular level through the enrichment of relevant molecular pathways associated with DCM. Furthermore, the phenotype of the core genes was validated to further support the results of the bioinformatics analysis through basic and clinical experiments. Additionally, the role of glucocorticoids in DCM treatment is discussed in this article with the purpose of providing a theoretical and experimental basis for exploring the pathogenesis of DCM and elucidating therapeutic methods. This study also provides a theoretical reference for the interpretation, early diagnosis, and treatment of DCM.

[18] Role of Recombinant Proteins for Treating Rheumatoid Arthritis

• Authors: Mahboubeh Soleimani Sasani, Y. Moradi
• Year: 2024
• Venue: Avicenna Journal of Medical Biotechnology
• URL: https://www.semanticscholar.org/paper/455e132608b909e67ea29486bb151fb6d4a3ef6c
• DOI: 10.18502/ajmb.v16i3.15739
• PMID: 39132628
• PMCID: 11316508
• Citations: 1
• Summary: The genetic and immunological factors that influence the development of RA, recombinant proteins, methods of using these proteins, approved drugs, and side effects associated with treating RA are discussed.
• Evidence snippets:
• Snippet 1 (score: 0.325) > Rheumatoid Arthritis (RA) is a chronic inflammatory disease that affects synovial joints and leads to pain, stiffness, and reduced mobility. Although the exact cause of this disease is not fully known, it appears to be an autoimmune disease in which the immune system mistakenly attacks the body's tissues. This problem is the result of a combination of genetic factors, the environment, and the immune system. RA is a complex disease involving both resident cells and infiltrating cells in membrane tissue 1 . In this disease, significant amounts of new vessels are formed in the membrane tissue, facilitating invasion by lymphocytes and monocytes and transforming a cell-free, loose cavity membrane into an abnormal, tumor-like invasive tissue. Micro vessels proliferate, forming straight vessels and branching regularly 1 . Studies have shown that the synovial fluid in patients with RA is highly inflamed in all joints and expresses much inflammatory genes 2 . The pathophysiology of RA is heterogeneous and includes defects in the innate and adaptive immune systems, genetic and environmental factors, autoantibodies, cellular changes, signaling pathways, and metabolism 1 . Understanding the role of individual variations in the cellular and molecular mechanisms associated with RA will significantly improve clinical care and patient outcomes. Individualized responses to standard therapy are observed in RA because of pathophysiological heterogeneity, ultimately leading to poor overall prognosis 2 . Key cellular and molecular findings in RA include angiogenesis, B cells, fibroblasts, reduced oxygen levels, synovial tissue, and T cells. Researchers are investigating altered metabolic pathways underlying synovial inflammation in RA 1 . The molecular and cellular heterogeneity of RA is a hot topic, and understanding the underlying mechanisms may lead to therapeutic intervention 3 . RA is currently treated worldwide to reduce inflammation, relieve pain, and slow the progression of joint damage. Conventional treatments include nonsteroidal anti-inflammatory drugs, diseasemodifying antirheumatic drugs, and biological agents, and in recent years, recombinant proteins have emerged as promising biological agents that can target specific proteins or cells involved in the inflammatory response 4 . Recombinant proteins are synthetic proteins that are produced in the laboratory using genetic engineering techniques.

[19] Focus on Achalasia in the Omics Era

• Authors: Anna Laura Pia Di Brina, O. Palmieri, Anna Lucia Cannarozzi, F. Tavano, Maria Guerra et al.
• Year: 2024
• Venue: International Journal of Molecular Sciences
• URL: https://www.semanticscholar.org/paper/650bd88078a05683426d4e086abaa2c68729b07d
• DOI: 10.3390/ijms251810148
• PMID: 39337632
• PMCID: 11431880
• Citations: 2
• Summary: This narrative review of the scientific literature is aimed to provide a comprehensive assessment of the state-of-the-art knowledge on omics of achalasia, with particular attention to those considered relevant to the pathogenesis of the disease.
• Evidence snippets:
• Snippet 1 (score: 0.325) > Basically all diseases, and not just so-called "complex diseases", are multifaceted because countless interconnected biological components contribute to their pathophysiology [8]. Any pathology has an intricate mix of genetic, epigenetic, environmental and behavioral factors that determine their onset and progression. Consequently, it is evident that studying each component of the disease in isolation, although it gives valuable information on any markers or sheds light on the different biological pathways between patients with a disease and a control group, is not sufficient to understand the intricate biological mechanisms at play [9]. For example, analysis of a single gene can reveal mutations associated with a disease, but cannot explain the entire clinical picture without considering the interaction of that gene with other genes, proteins and metabolites within the biological network. > So the need to study all components in a much more comprehensive way has emerged, hence the emphasis on omes and omics, defined, respectively, as the object of study of such field and its analysis. Substantially, omics is intended to improve our understanding of human biology and promote health and well-being through biomedical science and research [10]. Examples of omics disciplines include the identification of genes (genomics), messenger RNA (transcriptomics), epigenetic factors (epigenomics), proteins (proteomics) and finally, metabolites (metabolomics). > Thus ideally, different technologies would be combined to help diagnose disease and to generate effective clinically actionable tools to aid medical decision-making, generating a holistic picture of human phenotypes and disease. Furthermore, the integration of various types of omics data, multi-omics and clinical data, enables the production of more detailed information and is commonly used to discover potential underlying changes that trigger diseases contributing to the understanding of the pathogenic mechanisms or to identify potential targets for treatments. Indeed, it is expected that omics data will help the development of new and effective drugs, aimed at identifying biomarkers, novel molecular or protein targets for disease-modifying therapies useful for early diagnosis, disease staging and prediction progression. The National Cancer Institute defined biomarkers as biological molecules in blood, bodily fluids, or tissues that reveal whether a process, condition, or disease is normal or aberrant.

[20] In Vitro Disease Models of the Endocrine Pancreas

• Authors: Marko Milojević, Jan Rožanc, Jernej Vajda, Laura Činč Ćurić, Eva Paradiž et al.
• Year: 2021
• Venue: Biomedicines
• URL: https://www.semanticscholar.org/paper/607e4baf1df4c1c06656a07d617a408d29b1a3e8
• DOI: 10.3390/biomedicines9101415
• PMID: 34680532
• PMCID: 8533367
• Citations: 9
• Summary: This review provides an overview of in vitro models and focuses specifically on in vitro disease models of the endocrine pancreas and diabetes, with an emphasis on islets of Langerhans and beta cell dysfunction.
• Evidence snippets:
• Snippet 1 (score: 0.324) > The fundamental goal of biomedical research is to decipher the molecular mechanisms of human disease in order to develop more effective or even new models for diagnosis, prevention, and therapeutic approaches.Due to ethical and other concerns, basic research on human (patho)physiology requires in vitro approaches.Current experiments generally rely on cell cultures and animal models (e.g., transgenic mice).While these are useful for certain aspects of disease modelling because they replicate disease phenotypes similar those observed in humans, it is becoming increasingly clear that basic genetic and molecular mechanisms may differ greatly between humans and other animals due to species-specific differences.For example, a recent systematic study of 5554 human genes and 4918 murine analogues showed that, in acute inflammatory stress responses changes in murine gene expression correlate poorly with those observed in humans [1].Moreover, it is difficult to identify and independently vary the crucial molecular and cellular factors that contribute to disease in whole-animal models.This is probably the reason that many drugs fail to show efficacy and safety when translated from animal studies to human clinical trials [2]. > The inadequacies of animal models to adequately recapitulate human disease, coupled with the associated ethical constraints and requirements to study disease pathogenesis under controlled conditions, have given rise to a new field at the interface of tissue engineering and pathophysiology, focused on the development of in vitro models of disease.These are defined as synthetic alternative experimental systems that contain living human cells and mimic tissue-and organ-level pathophysiology in vitro by taking advantage of recent advances in tissue engineering, microfabrication, and microfluidics [3][4][5].When developing an in vitro disease model, some of the basic elements to consider are the source and type of cells, chemical and physical stimuli that promote the simulated cell phenotype, and additionally, when developing a 3D in vitro model, scaffold structure, fabrication process, and building blocks.The micro-and macro-environmental conditions of the in vitro models should be designed to mimic the characteristics of native or pathologically altered tissues.These include nutrient and metabolite concentrations, pH, and gas and mechanical gradients [6,7].

Notes

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