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Hypochondrogenesis

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Hypochondrogenesis. Core disease mechanisms, molecular and cellular pathwa...

2026-04-02
Asta MONDO:0019669 Model: Asta Scientific Corpus Retrieval 20 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Hypochondrogenesis. Core disease mechanisms, molecular and cellular pathwa...

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

  • Papers retrieved: 20
  • Snippets retrieved: 20

Relevant Papers

[1] 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: 37
  • 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: 0.453) > 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.

[2] 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: 0.407) > 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.

[3] COL2A1 Gene Mutations: Mechanisms of Spondyloepiphyseal Dysplasia Congenita

  • Authors: R. Nenna, A. Turchetti, G. Mastrogiorgio, F. Midulla
  • Year: 2019
  • Venue: The Application of Clinical Genetics
  • URL: https://www.semanticscholar.org/paper/11570930acf0acf11d460fbedbda787a1c71e000
  • DOI: 10.2147/TACG.S197205
  • PMID: 31824186
  • PMCID: 6900288
  • Citations: 33
  • Influential citations: 2
  • Summary: The COL2A1 gene consists of 54 exons spanning over 31.5 kb and encodes for type II collagen, which is the main component of hyaline cartilage extracellular matrix, nucleus pulposus of intervertebral discus, vitreous humor of the eye and inner ear structure and more.
  • Evidence snippets:
  • Snippet 1 (score: 0.405) > Missense mutations leading to other amino acids than glycine substitution causes generally milder phenotype due to impairment in protein stability, and subsequent damage in helical structure and proper function of type II collagen. > Haploinsufficiency is a mechanism due to non-sense substitutions or out-of-frame deletions, resulting in premature stop codons which cause reduced synthesis of normal collagen. These mutations are associated with milder phenotypes. > Furthermore, phenotypic variation is likely caused by environmental factors and the polymorphisms in diseasemodifying genes and/or regulatory elements. > Type II collagenopathies clinical features show a wide range of severity and complexity. > Moreover, several type II collagenopathies clinical features are shared by other syndromes due to defects in other components of cartilage (eg, otospondylomegaepiphyseal dysplasia caused by COL11A2 mutation, multiple epiphyseal dysplasia principally caused by COMP mutation). 10,11 henotypic overlap in COL2A1-related disorders and wide inter-and intra-familiar phenotypic variation have been commonly reported. > At one end of the spectrum, achondrogenesis type II (ACG2)/hypochondrogenesis and platyspondylic lethal skeletal dysplasia, Torrance type (PLSDT) are perinatally lethal conditions. They are characterized by micromelia, narrow chest with pulmonary hypoplasia, absent ossification of vertebras bodies and sacrum, Pierre Robin sequence and several visceral anomalies. At the other end of the spectrum are listed some conditions typical of adolescent or adult age: avascular necrosis of the femoral head (ANFH), Legg-Calvè-Perthes disease, early-onset osteoarthritis (OA), Strickler syndrome type1 (STL1), vitreoretinopathy with phalangeal epiphyseal dysplasia (VPED). These conditions are characterized by normal stature and early development of arthrosis or ocular defects.

[4] 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: 0.390) > 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.

[5] Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response

  • Authors: P. Mesdom, R. Colle, É. Lebigot, S. Trabado, Eric Deflesselle et al.
  • Year: 2020
  • Venue: Current Neuropharmacology
  • URL: https://www.semanticscholar.org/paper/79368e365458486de96794333613c12a6063bf54
  • DOI: 10.2174/1570159X17666191021141057
  • PMID: 31631822
  • PMCID: 7327943
  • Citations: 12
  • Summary: This review highlights the great and still underused potential of HDF, which stands out as a very promising tool in the understanding of MDD and AD mechanisms of action.
  • Evidence snippets:
  • Snippet 1 (score: 0.379) > Background: Human dermal fibroblasts (HDF) can be used as a cellular model relatively easily and without genetic engineering. Therefore, HDF represent an interesting tool to study several human diseases including psychiatric disorders. Despite major depressive disorder (MDD) being the second cause of disability in the world, the efficacy of antidepressant drug (AD) treatment is not sufficient and the underlying mechanisms of MDD and the mechanisms of action of AD are poorly understood. Objective The aim of this review is to highlight the potential of HDF in the study of cellular mechanisms involved in MDD pathophysiology and in the action of AD response. Methods The first part is a systematic review following PRISMA guidelines on the use of HDF in MDD research. The second part reports the mechanisms and molecules both present in HDF and relevant regarding MDD pathophysiology and AD mechanisms of action. Results HDFs from MDD patients have been investigated in a relatively small number of works and most of them focused on the adrenergic pathway and metabolism-related gene expression as compared to HDF from healthy controls. The second part listed an important number of papers demonstrating the presence of many molecular processes in HDF, involved in MDD and AD mechanisms of action. Conclusion The imbalance in the number of papers between the two parts highlights the great and still underused potential of HDF, which stands out as a very promising tool in our understanding of MDD and AD mechanisms of action

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

  • Authors: R. Ragusa, Pasquale 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: 3
  • 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: 0.376) > 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.

[7] Direct Sarcomere Modulators Are Promising New Treatments for Cardiomyopathies

  • Authors: O. Tsukamoto
  • Year: 2019
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/07467943fe92ce135b52ded5e5dea2bfc2ddf179
  • DOI: 10.3390/ijms21010226
  • PMID: 31905684
  • PMCID: 6982115
  • Citations: 16
  • Summary: The direct inhibition of sarcomere contractility may be able to suppress the development and progression of HCM with hypercontractile mutations and improve clinical parameters in patients with HCM, and direct activation of sar COMs modulators that can positively influence the natural history of cardiomyopathies represent promising treatment options.
  • Evidence snippets:
  • Snippet 1 (score: 0.372) > Hereditary DCM can be caused by single point mutations in sarcomere proteins. However, the link between point mutations and clinical phenotypes in DCM is not thoroughly understood in most cases. Recent advances in biochemical, biophysical, stem cell, and gene editing technologies have provided a better understanding of the molecular mechanisms through which the initial insult in DCM (i.e., mutations in a sarcomere protein) induces alterations in cellular organization and contractility, resulting in disease phenotypes. In particular, hiPSC-CMs and genetically modified animals are excellent models because they can capture the initial molecular phenotype that occurs before major compensatory mechanisms mask it.

[8] 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: 7
  • 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: 0.370) > 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.

[9] 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: 0.369) > 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) [

[10] 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.

[11] Chondroprotective Factors in Osteoarthritis: a Joint Affair

  • Authors: J. Mimpen, Sarah J B Snelling
  • Year: 2019
  • Venue: Current Rheumatology Reports
  • URL: https://www.semanticscholar.org/paper/8e9758d948f6d821fc10bacf365a2bf1e9efd5f4
  • DOI: 10.1007/s11926-019-0840-y
  • PMID: 31227927
  • PMCID: 6588640
  • Citations: 26
  • Influential citations: 1
  • Summary: Chondroprotection requires a whole joint approach, stratification of patient groups, and use of patient-relevant end points, while using modern technologies and recent knowledge to re-visit unsuccessful therapeutics from the past.
  • Evidence snippets:
  • Snippet 1 (score: 0.363) > Cellular or molecular signatures may not have functional effects on cartilage damage or OA pathobiology and may instead simply postcode a disease state or subtype. Therefore, successful delivery of chondroprotection relies on well-conducted functional studies and on the extension of cross-sectional and longitudinal studies of OA endotypes-all informed by clinical signs and risk factors. Tissues across the whole joint plus urine, blood, and synovial fluid should be incorporated. Cellular and molecular signatures of tissues obtained from diseased joints, healthy joints and joints following t herapeutic intervention are also essential. These signatures will enable identification of underlying mechanisms of disease and produce meaningful readouts to assess whether an intervention results in a "healthy" or "effectively treated" signature. The use of the spectrum of relevant tissues and fluids allows more robust endotype identification, while identifying less invasive surrogates for tissuebased signatures. Stratification panels will undergo continuous evolution, changing not only with disease subset but also with the stage of cartilage damage and other clinical readouts and risk-factors. The key stratification categories should be applied to studies of disease development and to pre-clinical and clinical drug development pathways. To refine critical stratification measures and identify relevant end points for pre-clinical and clinical studies, nextgeneration sequencing, "omics", and cytometry approaches should be integrated with risk factors, clinical signs and symptoms. Tissue-based end points and stratification measures should be derived using well-phenotyped healthy and diseased tissues from the joint. Where appropriate, embedding tissue collection and analysis within enrolment and outcome stages of clinical trials would inform future studies across the translational cycle Studies of disease mechanisms, drug target identification, and drug testing rely on in vitro and in vivo methods, supplemented with in silico and mathematical modeling, to identify key drivers, stratification sets, and end points. Functional assays and modeling of identified biomarkers, cell types, and molecular signatures will enable validation of potential targets for chondroprotective agents and testing of therapeutic efficacy. Models and end points used in vitro and in vivo need to account for differing endotypes and changing molecular signatures associated with OA progression or cessation. As with human disease, these models should not be cho

[12] Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis

  • Authors: J. Steinberg, G. R. S. Ritchie, T. Roumeliotis, R. Jayasuriya, M. J. Clark et al.
  • Year: 2016
  • Venue: Scientific Reports
  • URL: https://www.semanticscholar.org/paper/24d776d78df1edd8fdb3ef4094650dfcea0dc4f2
  • DOI: 10.1038/s41598-017-09335-6
  • PMID: 28827734
  • PMCID: 5566454
  • Citations: 112
  • Influential citations: 4
  • Summary: Through integration of genome-wide methylation, gene and protein expression data in human primary chondrocytes, consistent molecular players in OA progression that replicated across independent datasets and that have translational potential are identified.
  • Evidence snippets:
  • Snippet 1 (score: 0.362) > are joint-independent. > Notably, this study is a proof-of-concept for integrative deep molecular phenotyping across methylation, gene expression, and protein abundance. As such, it was not powered to provide an exhaustive list of molecular targets and pathways. Indeed, we estimate that only ~10% of the true differentially expressed genes are statistically significant in this study (Supplementary Fig. S5). The sample size could also affect the degree of overlap and agreement between the methylation, gene expression, and protein abundance (this overlap could also be affected by difficulties in assigning the effects of methylation changes to genes: for example, it is possible that the expression of a gene is affected by methylation changes in a distal enhancer, or that a given gene contains an enhancer region for a different gene, and thus methylation of the first gene also affects the expression of the second). Larger sample sizes will be required for a more powerful characterisation of the molecular changes occurring with disease progression. Moreover, investigations of further OA-relevant cell types (including synoviocytes and adipocytes) will be necessary to identify disease-related changes in other tissues, and the biological mechanisms specific to such tissues. > In summary, the integrative functional genomics approach undertaken here has identified biological changes in disease-relevant tissues, highlighting three genes and several pathways that are involved on all three levels examined. Moreover, the approach identified nine genes with changes on multiple molecular levels that are already targeted by drugs approved for human use, highlighting the potential of discovering targets for intervention. These drugs have established safety profiles and pharmacokinetic data for use in humans, which would shorten the investigative pipeline to clinical use in OA. These agents cover a broad range of mechanisms of action and represent novel investigational targets for 'first in disease' studies of OA progression. Further studies will be necessary to comprehensively characterize the molecular signatures of OA.

[13] 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: 110
  • 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: 0.362) > 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.

[14] Bioinformatics analysis of ferroptosis in frozen shoulder

  • Authors: Hongcui Zhang, Jiahua Zhou, ZhiHua Liu, Kaile Wang, Hexun Jiang
  • Year: 2024
  • Venue: BMC Medical Genomics
  • URL: https://www.semanticscholar.org/paper/add3fea4459c4cf693f0de24972672a849a78bbc
  • DOI: 10.1186/s12920-024-02011-5
  • PMID: 39334338
  • PMCID: 11428309
  • Summary: The results demonstrated that ferroptosis may affect the pathological process of frozen shoulders through these signaling pathways and genes.
  • Evidence snippets:
  • Snippet 1 (score: 0.361) > Frozen shoulder (FS), also known as adhesive capsulitis, is a chronic condition characterized by pain, stiffness, and restricted range of motion of the shoulder joint [1]. This condition can have a significant impact on patients' quality of life, limiting their ability to perform daily activities and causing significant discomfort [2]. The precise etiology of frozen shoulders remains unclear, however, accumulating evidence suggests that dysregulation of cellular processes, including inflammation and oxidative stress, may play a vital role in its pathogenesis [3]. > In recent years, bioinformatics has made significant progress in understanding the molecular mechanisms underlying various diseases [4]. Bioinformatic tools and techniques have enabled the integration of vast amounts of data generated from different experimental platforms, providing valuable insights into the complex biological processes that lead to disease development [5]. Bioinformatics has revealed novel therapeutic targets and potential drug candidates for various diseases by analyzing gene expression profiles, protein networks, and pathway interactions [6]. > Ferroptosis is a regulatory cell death process driven by iron-dependent lipid peroxidation and is involved in the pathological and physiological processes of various diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases [7,8]. In this study, we aim to use bioinformatics analyses to investigate the potential role of ferroptosis in the pathophysiology of frozen shoulders. By integrating transcriptomic data from patients with frozen shoulders, we hope to identify the molecular signatures associated with ferroptosis under these conditions. This approach will enable us to gain a more comprehensive understanding of the underlying mechanisms involved in frozen shoulders and the potential role of ferroptosis in its development and progression. This is the first study to explore the complex relationship between ferroptosis and frozen shoulders, and our research may lead to the discovery of novel therapeutic targets that can effectively manage this musculoskeletal condition. By understanding the underlying mechanisms that drive ferroptosis in frozen shoulders, innovative treatment strategies that target these specific pathways can be designed. Such targeted approaches may offer patients more personalized and effective treatment options, leading to improved outcomes and quality of life. Furthermore, our findings could contribute to a better understanding of the pathogenesis of frozen shoulders.

[15] Landscape analysis for a neonatal disease progression model of bronchopulmonary dysplasia: Leveraging clinical trial experience and real-world data

  • Authors: J. Barrett, Megan Cala Pane, Timothy D. Knab, W. Roddy, J. Beusmans et al.
  • Year: 2022
  • Venue: Frontiers in Pharmacology
  • URL: https://www.semanticscholar.org/paper/1b1552b5a3b6bd9f225ecce6435d9972f160e6b4
  • DOI: 10.3389/fphar.2022.988974
  • PMID: 36313352
  • PMCID: 9597633
  • Citations: 2
  • Summary: A landscape of the data is defined including targeted literature searches and solicitation of neonatal RWD sources for context-of use (COU)-driven models and analysis plans to develop a family of models of BPD in neonates, leveraging previous clinical trial experience and real-world patient data are described.
  • Evidence snippets:
  • Snippet 1 (score: 0.357) > Techniques to measure biological events and mechanisms have not been delineated or deployed at sufficient scale to provide a comprehensive "map" of the condition. Similarly, clinical events have not been defined other than a variety of short-and long-term endpoints. Clinical observations are not informed by the timing or nature of biological processes or mechanisms. In other conditions, information about the stages of pathophysiology (biological processes) and clinical events inform the development of therapeutic options. Data from biological and clinical sources, summarized in Figure 2, can be combined in "disease progression models" (DPM) that capture the stages of disease development, the timing of the stages, and the extent of variation between individuals in the pathway to disease. DPM are a key tool in drug development allowing rational targeting of interventions and evidencebased planning of clinical trials (Fouarge et al., 2021;Barrett et al., 2022). Here we review the DPM concept applied to strategies for the development of a BPD DPM. This manuscript seeks to both prospectively assess the potential of the clinical real-world data to inform BPD (and therefore, other complications of extreme prematurity) definition and also the potential of utilizing such data to construct models that would inform BPD drug development as a context of use. Selected references identified by this search were supplemented by papers from the authors' collections and identification of additional resources among subject matter experts from the INC. The INC BPD working group and modeling and simulation subteam filtered the literature search results into categories that would include one of the following: relevant data from which model priors could be abstracted, published models of various types (e.g., predictive, descriptive, mechanistic, etc.), descriptive and/or quantitative definitions of BPD to be used as comparators for a future definition.

[16] Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

  • Authors: L. Velicki, D. Jakovljevic, A. Preveden, M. Golubovic, M. Bjelobrk et al.
  • Year: 2020
  • Venue: BMC Cardiovascular Disorders
  • URL: https://www.semanticscholar.org/paper/5b4558af699aad557a802ddc5c280ae601c2d56f
  • DOI: 10.1186/s12872-020-01807-4
  • PMID: 33297970
  • PMCID: 7727200
  • Citations: 55
  • Influential citations: 2
  • Summary: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.
  • Evidence snippets:
  • Snippet 1 (score: 0.356) > ]. Technological progress has made it possible to identify new genes associated with HCM-numerous other genes that do not encode sarcomere proteins but rather genes encoding the synthesis of Z-disk proteins and proteins involved in the calcium signaling pathway. With the introduction and implementation of the next-generation sequencing solutions, the identification of nearly 50 gene mutations associated with some form of HCM throughout literature has become possible [12]. > Regardless of the mutation type, the same pathophysiology mechanisms are responsible for the development of typical HCM phenotype and disease progression. Disrupted sarcomere properties due to the mutations cause impaired relaxation and lead to diastolic dysfunction, which is followed by hyperdynamic contractility and hypertrophy of the LV in the later course [9,11]. > Due to variable penetrance and expressivity, the phenotypic characteristics of HCM are multifaceted and may be influenced by other factors beyond single pathogenic mutations [13]. In addition to LV hypertrophy, phenotypic HCM expression also includes myocardial hypercontractivity, myofibril disorganization, fibrosis, as well as the presence of mild myocardial inflammation. Although the clinical phenotype can partially differ depending on the affected gene, no distinctive correlation between disease severity and specific genes has been established. Moreover, clinical features such as disease penetration, hypertrophy severity, and patient prognosis are known to vary depending on different mutations within the same gene [11]. > The precise link between determined underlying gene mutation and the clinical course remains elusive in this heterogeneous condition. The motivation to compile this HCM patient registry was to try to define what patient features are more prevalent with specific gene mutations and to establish whether the level of disease expression might be linked to one of the two most common mutations responsible for HCM. The goal was to reveal and distinguish subtle differences that may exist in clinical presentation and, more importantly, in heart structure and function recorded by cardiac imaging (i.e. echocardiography) between different gene mutations, thus providing essential information for the computational model development. Moreover, data from this study will also complement the clinical trial (NCT03832660 at clinicaltrials.gov) evaluating the effects of pharmacological (sacub

[17] 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: 0.356) > 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.

[18] Knee Osteoarthritis—How Close Are We to Disease-Modifying Treatment: Emphasis on Metabolic Type Knee Osteoarthritis

  • Authors: S. Lambova
  • Year: 2023
  • Venue: Life
  • URL: https://www.semanticscholar.org/paper/40481a4f18e0f7795a5386b8c4b1711d9c98845f
  • DOI: 10.3390/life13010140
  • PMID: 36676089
  • PMCID: 9866724
  • Citations: 5
  • Summary: Osteoarthritis (OA) is a whole-joint disease that affects cartilage, bone, and synovium as well as ligaments, menisci, and muscles [...].
  • Evidence snippets:
  • Snippet 1 (score: 0.355) > The heterogeneous nature of OA regarding localization and its dominant pathogenic mechanism are the major causes for unsatisfactory therapeutic results in relation to slowing of structural progression. The standard pharmacological treatments used in OA are nonsteroidal anti-inflammatory drugs, analgesics, and symptomatic, slow-acting agents with chondroprotective properties (e.g., glucosamine, chondroitin, soy and avocado, and intraarticular hyaluronic acid) [2,3]. > The knee is the most commonly affected joint in OA. The existence of different phenotypes of knee OA has been suggested; however, the precise criteria for their classification are not well-defined. While clinical phenotypes are characterized by common risk factors and can be used to determine progression and predict therapeutic response, the endotypes are disease subtypes characterized by well-defined molecular mechanisms, i.e., cellular and biochemical signaling pathways [4]. > Based on a systematic literature review, Dell'Isola et al. (2016) have proposed the existence of six phenotypes of knee OA related to predominant pathogenic mechanisms, i.e., a chronic pain phenotype, an inflammatory phenotype, phenotypes associated with alterations in bone and cartilage metabolism, with metabolic syndrome, a mechanical phenotype, and minimal joint disease. The chronic pain phenotype is thought to be related to central sensitization and alterations in pain neurophysiology and the psychological profile. Regarding the inflammatory type of knee OA, gene overexpression of inflammatory cytokines was detected, e.g., interleukin (IL)-1β, cyclooxygenase 2, and macrophage-inflammatory proteins. Higher level of pain and faster radiographic progression were observed in these cases compared to those with low cytokine expression. In the metabolic type of knee OA, it has been suggested that metabolic syndrome contributes to the development of knee OA, and this phenotype has been associated with higher levels of leptin and high-sensitivity CRP (hsCRP).

[19] Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies

  • Authors: J. Casanova, M. Conley, S. Seligman, L. Abel, L. Notarangelo
  • Year: 2014
  • Venue: The Journal of Experimental Medicine
  • URL: https://www.semanticscholar.org/paper/6f6b8309ebce06da91e67c72a535694969115597
  • DOI: 10.1084/jem.20140520
  • PMID: 25311508
  • PMCID: 4203950
  • Citations: 235
  • Influential citations: 5
  • Summary: The importance of single-patient genetic studies in the discovery of novel primary immunodeficiencies and insight into the standards and criteria that should accompany these studies are offered.
  • Evidence snippets:
  • Snippet 1 (score: 0.353) > a. A variant in a protein-coding gene can be nonsynonymous (change the amino acid sequence) or, if synonymous, have a proven impact on mRNA structure or amount (e.g., create an abnormal splicing site). A variant in an RNA gene must affect its function (if its expression is detectable). > b. Studies should document whether the variant changes the amount or molecular weight of the gene transcript and of the encoded protein. Ideally, this should be done in control primary cells or iPSC-derived cell lines, and not only in control immortalized cell lines. > c. Computer programs that predict whether a missense variant is damaging are helpful but not conclusive. A variation that is not conservative and that occurs in a region or at a residue of the encoded protein that is highly conserved in evolution provides support for the hypothesis that the amino acid is functionally important. > d. The variants must be loss or gain of function for at least one biological activity. For variants that result in an amino acid substitution, insertion, or deletion, in vitro studies should document a functional change that reveals the mechanism by which the variant causes disease. For example, the protein may be unstable, it may not bind essential cofactors, or it may not localize appropriately. > 3. The causal relationship between the candidate genotype and the clinical phenotype must be established via a relevant cellular or animal phenotype. > a. In all cases, the candidate gene should be known or shown to be normally expressed in cell types relevant to the disease process. These may be cells affected by the disease process, cells which produce factors needed by the affected cells or progenitors of the cell lineage affected by the disease. Some genes are broadly expressed but have a narrow clinical phenotype. > b. For disorders that affect the function of a cell (present in the patient), experimental studies in vitro must indicate that there is a cellular phenotype explained by the candidate genotype (see c). This cellular phenotype should reasonably account for the clinical phenotype because the cell type is known to be involved in the disease process and the clinical phenotype is consistent with it. For example, if the candidate gene can be connected to a known disease-causing gene via a common cellular phenotype (e.g., mutations

[20] Structural, cellular and molecular mechanisms involved in the Epithelial-to-Mesenchymal Transition in Cancer

  • Authors: Moniri Javadhesari, Vaezi Heris
  • Year: 2022
  • Venue: Journal of Cell and Tissue
  • URL: https://www.semanticscholar.org/paper/0e5acf2d67a761fb70d6a28a6f6f60fbe88abcf2
  • DOI: 10.52547/jct.13.2.71
  • Summary: EMT plays a crucial role in cancer progression, crossing the cells through the biological and body barriers, and metastasis that are usually associated with poor prognosis of cancer patients.
  • Evidence snippets:
  • Snippet 1 (score: 0.351) > Epithelial-Mesenchymal Transition, Carcinogenesis, Gene Expression Regulation, Tumor Microenvironment. Intoduction: Cancer as one of the most common genetic diseases is the leading cause of death worldwide. Cancer cells undergo various genetic and phenotypic changes to spread and survive. In the early stages, these changes lead to the development of tumor, while at the advanced stages they can provide a suitable pre-metastatic microenvironment in which various uncontrolled events occur including cell proliferation, traversing through the extracellular matrix, and crossing barriers to enter the bloodstream. Extracellular changes in this microenvironment can induce intracellular changes in primary cancer cells that assist in the sustainability and propagation of these cells. Complicated interactions between the external and internal factors result in the establishment of various regulatory networks between different types of carcinogenesis promoting factors. Identification of these modifications plays a critical role in understanding the mechanisms of disease progression, prognosis and management. Text: Various mutations and differential gene expression trigger metastasis of cancer cells by epithelial to mesenchymal transition (EMT) mechanism, among which the role of chromatin structural changes, intracellular signal transduction pathways, regulation of cell cycle and microRNAs, and genomic instability has been reported. The alterations in gene expression patterns of mentioned pathways lead to potential regulatory complications that faced the management of disease progression and response to therapies with problems. Cancer cells provide their requirements by neutralizing biological barriers, modifying the regulation of inhibiting processes of cancer progression, establishing de novo endogenous mechanisms and providing specialized molecular and structural markers, and various combinations of these methods have been demonstrated in different types of cancer. Furthermore, EMT and Structural, cellular and molecular mechanisms involved in the Epithelial-to-Mesenchymal Transition in Cancer Journal of Cell and Tissue 13(2) (2022) 71-94 cancer stem cells (CSCs) have a mutual relationship in which the presence of one assists the occurrence of the other. Altogether, cancer cells take the advantage of multiple approaches including upregulation of main transcription factors such as snail, slug, Foxc2, Twist and ZEB1/2, benefiting the mechanisms of telomere length protection, production of CD133,CD44 and BMI1 biomark

Notes

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