LIVIVO - Search results -

Search results

Result 1 - 10 of total 31

Search options

Article ; Online: Gas Chromatography-Mass Spectrometry and Analysis of the Serum Metabolomic Profile Through Extraction and Derivatization of Polar Metabolites.

Rattner, Jodi / Farshidfar, Farshad / Bathe, Oliver F

Methods in molecular biology (Clifton, N.J.)

2019 Volume 1928, Page(s) 235–249

Abstract: Metabolite profiling in complex biological matrices such as serum requires high-throughput technologies capable of accurate and reproducible quantitative analysis and detection of slight differences in metabolite concentrations. Gas chromatography-mass ... ...

Abstract	Metabolite profiling in complex biological matrices such as serum requires high-throughput technologies capable of accurate and reproducible quantitative analysis and detection of slight differences in metabolite concentrations. Gas chromatography-mass spectrometry (GC-MS) is widely used for characterizing the metabolome. This chapter summarizes the necessary preparatory steps required to profile the metabolome using GC-MS. While this chapter focuses on evaluating polar metabolites in serum samples, the methods can be adapted to quantify nonpolar metabolites in other biological matrices.
MeSH term(s)	Biomarkers/blood ; Data Analysis ; Gas Chromatography-Mass Spectrometry ; Humans ; Metabolome ; Metabolomics/methods ; Neoplasms/blood ; Neoplasms/metabolism ; Software
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-02-06
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9027-6_13
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: From genotype to functional phenotype: unraveling the metabolomic features of colorectal cancer.

Bathe, Oliver F / Farshidfar, Farshad

Genes

2014 Volume 5, Issue 3, Page(s) 536–560

Abstract: Much effort in recent years has been expended in defining the genomic and epigenetic alterations that characterize colorectal adenocarcinoma and its subtypes. However, little is known about the functional ramifications related to various subtypes. ... ...

Abstract	Much effort in recent years has been expended in defining the genomic and epigenetic alterations that characterize colorectal adenocarcinoma and its subtypes. However, little is known about the functional ramifications related to various subtypes. Metabolomics, the study of small molecule intermediates in disease, provides a snapshot of the functional phenotype of colorectal cancer. Data, thus far, have characterized some of the metabolic perturbations that accompany colorectal cancer. However, further studies will be required to identify biologically meaningful metabolic subsets, including those corresponding to specific genetic aberrations. Moreover, further studies are necessary to distinguish changes due to tumor and the host response to tumor.
Language	English
Publishing date	2014-07-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes5030536
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: A clinically useful and biologically informative genomic classifier for papillary thyroid cancer.

Craig, Steven / Stretch, Cynthia / Farshidfar, Farshad / Sheka, Dropen / Alabi, Nikolay / Siddiqui, Ashar / Kopciuk, Karen / Park, Young Joo / Khalil, Moosa / Khan, Faisal / Harvey, Adrian / Bathe, Oliver F

Frontiers in endocrinology

2023 Volume 14, Page(s) 1220617

Abstract: Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features, is inaccurate. We applied a machine learning algorithm ( ...

Abstract	Clinical management of papillary thyroid cancer depends on estimations of prognosis. Standard care, which relies on prognostication based on clinicopathologic features, is inaccurate. We applied a machine learning algorithm (
MeSH term(s)	Humans ; Thyroid Cancer, Papillary/diagnosis ; Thyroid Cancer, Papillary/genetics ; Thyroid Neoplasms/diagnosis ; Thyroid Neoplasms/genetics ; Thyroid Neoplasms/pathology ; Carcinoma, Papillary/pathology ; Iodine Radioisotopes ; Proto-Oncogene Proteins B-raf/genetics ; Genomics ; Tumor Microenvironment
Chemical Substances	Iodine Radioisotopes ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1)
Language	English
Publishing date	2023-09-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1220617
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: A Framework for Development of Useful Metabolomic Biomarkers and Their Effective Knowledge Translation.

Marchand, Calena R / Farshidfar, Farshad / Rattner, Jodi / Bathe, Oliver F

Metabolites

2018 Volume 8, Issue 4

Abstract: Despite the significant advantages of metabolomic biomarkers, no diagnostic tests based on metabolomics have been introduced to clinical use. There are many reasons for this, centered around substantial obstacles in developing clinically useful ... ...

Abstract	Despite the significant advantages of metabolomic biomarkers, no diagnostic tests based on metabolomics have been introduced to clinical use. There are many reasons for this, centered around substantial obstacles in developing clinically useful metabolomic biomarkers. Most significant is the need for interdisciplinary teams with expertise in metabolomics, analysis of complex clinical and metabolomic data, and clinical care. Importantly, the clinical need must precede biomarker discovery, and the experimental design for discovery and validation must reflect the purpose of the biomarker. Standard operating procedures for procuring and handling samples must be developed from the beginning, to ensure experimental integrity. Assay design is another challenge, as there is not much precedent informing this. Another obstacle is that it is not yet clear how to protect any intellectual property related to metabolomic biomarkers. Viewing a metabolomic biomarker as a natural phenomenon would inhibit patent protection and potentially stifle commercial interest. However, demonstrating that a metabolomic biomarker is actually a derivative of a natural phenomenon that requires innovation would enhance investment in this field. Finally, effective knowledge translation strategies must be implemented, which will require engagement with end users (clinicians and lab physicians), patient advocate groups, policy makers, and payer organizations. Addressing each of these issues comprises the framework for introducing a metabolomic biomarker to practice.
Language	English
Publishing date	2018-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo8040059
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Targeting HDAC6 to treat heart failure with preserved ejection fraction in mice.

Ranjbarvaziri, Sara / Zeng, Aliya / Wu, Iris / Greer-Short, Amara / Farshidfar, Farshad / Budan, Ana / Xu, Emma / Shenwai, Reva / Kozubov, Matthew / Li, Cindy / Van Pell, Melissa / Grafton, Francis / MacKay, Charles E / Song, Xiaomei / Priest, James R / Argast, Gretchen / Mandegar, Mohammad A / Hoey, Timothy / Yang, Jin

Nature communications

2024 Volume 15, Issue 1, Page(s) 1352

Abstract: Heart failure with preserved ejection fraction (HFpEF) poses therapeutic challenges due to the limited treatment options. Building upon our previous research that demonstrates the efficacy of histone deacetylase 6 (HDAC6) inhibition in a genetic ... ...

Abstract	Heart failure with preserved ejection fraction (HFpEF) poses therapeutic challenges due to the limited treatment options. Building upon our previous research that demonstrates the efficacy of histone deacetylase 6 (HDAC6) inhibition in a genetic cardiomyopathy model, we investigate HDAC6's role in HFpEF due to their shared mechanisms of inflammation and metabolism. Here, we show that inhibiting HDAC6 with TYA-018 effectively reverses established heart failure and its associated symptoms in male HFpEF mouse models. Additionally, in male mice lacking Hdac6 gene, HFpEF progression is delayed and they are resistant to TYA-018's effects. The efficacy of TYA-018 is comparable to a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and the combination shows enhanced effects. Mechanistically, TYA-018 restores gene expression related to hypertrophy, fibrosis, and mitochondrial energy production in HFpEF heart tissues. Furthermore, TYA-018 also inhibits activation of human cardiac fibroblasts and enhances mitochondrial respiratory capacity in cardiomyocytes. In this work, our findings show that HDAC6 impacts on heart pathophysiology and is a promising target for HFpEF treatment.
MeSH term(s)	Animals ; Humans ; Male ; Mice ; Cardiomyopathies ; Heart Failure/drug therapy ; Heart Failure/genetics ; Heart Failure/diagnosis ; Histone Deacetylase 6/genetics ; Myocytes, Cardiac/metabolism ; Stroke Volume/physiology
Chemical Substances	HDAC6 protein, human (EC 3.5.1.98) ; Histone Deacetylase 6 (EC 3.5.1.98) ; Hdac6 protein, mouse (EC 3.5.1.98)
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45440-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Phenotypic screening with deep learning identifies HDAC6 inhibitors as cardioprotective in a BAG3 mouse model of dilated cardiomyopathy.

Yang, Jin / Grafton, Francis / Ranjbarvaziri, Sara / Budan, Ana / Farshidfar, Farshad / Cho, Marie / Xu, Emma / Ho, Jaclyn / Maddah, Mahnaz / Loewke, Kevin E / Medina, Julio / Sperandio, David / Patel, Snahel / Hoey, Tim / Mandegar, Mohammad A

Science translational medicine

2022 Volume 14, Issue 652, Page(s) eabl5654

Abstract: Dilated cardiomyopathy (DCM) is characterized by reduced cardiac output, as well as thinning and enlargement of left ventricular chambers. These characteristics eventually lead to heart failure. Current standards of care do not target the underlying ... ...

Abstract	Dilated cardiomyopathy (DCM) is characterized by reduced cardiac output, as well as thinning and enlargement of left ventricular chambers. These characteristics eventually lead to heart failure. Current standards of care do not target the underlying molecular mechanisms associated with genetic forms of heart failure, driving a need to develop novel therapeutics for DCM. To identify candidate therapeutics, we developed an in vitro DCM model using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) deficient in B-cell lymphoma 2 (BCL2)-associated athanogene 3 (BAG3). With these BAG3-deficient iPSC-CMs, we identified cardioprotective drugs using a phenotypic screen and deep learning. From a library of 5500 bioactive compounds and siRNA validation, we found that inhibiting histone deacetylase 6 (HDAC6) was cardioprotective at the sarcomere level. We translated this finding to a BAG3 cardiomyocyte-knockout (BAG3
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Apoptosis Regulatory Proteins/metabolism ; Cardiomyopathy, Dilated/diagnosis ; Cardiomyopathy, Dilated/drug therapy ; Cardiomyopathy, Dilated/genetics ; Deep Learning ; Disease Models, Animal ; Heart Failure/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/therapeutic use ; Mice ; Myocytes, Cardiac/metabolism ; Stroke Volume ; Ventricular Function, Left
Chemical Substances	Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; Bag3 protein, mouse ; Histone Deacetylase Inhibitors
Language	English
Publishing date	2022-07-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abl5654
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6941: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Deep learning detects cardiotoxicity in a high-content screen with induced pluripotent stem cell-derived cardiomyocytes.

Grafton, Francis / Ho, Jaclyn / Ranjbarvaziri, Sara / Farshidfar, Farshad / Budan, Anastasiia / Steltzer, Stephanie / Maddah, Mahnaz / Loewke, Kevin E / Green, Kristina / Patel, Snahel / Hoey, Tim / Mandegar, Mohammad Ali

eLife

2021 Volume 10

Abstract: Drug-induced cardiotoxicity and hepatotoxicity are major causes of drug attrition. To decrease late-stage drug attrition, pharmaceutical and biotechnology industries need to establish biologically relevant models that use phenotypic screening to detect ... ...

Abstract	Drug-induced cardiotoxicity and hepatotoxicity are major causes of drug attrition. To decrease late-stage drug attrition, pharmaceutical and biotechnology industries need to establish biologically relevant models that use phenotypic screening to detect drug-induced toxicity in vitro. In this study, we sought to rapidly detect patterns of cardiotoxicity using high-content image analysis with deep learning and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). We screened a library of 1280 bioactive compounds and identified those with potential cardiotoxic liabilities in iPSC-CMs using a single-parameter score based on deep learning. Compounds demonstrating cardiotoxicity in iPSC-CMs included DNA intercalators, ion channel blockers, epidermal growth factor receptor, cyclin-dependent kinase, and multi-kinase inhibitors. We also screened a diverse library of molecules with unknown targets and identified chemical frameworks that show cardiotoxic signal in iPSC-CMs. By using this screening approach during target discovery and lead optimization, we can de-risk early-stage drug discovery. We show that the broad applicability of combining deep learning with iPSC technology is an effective way to interrogate cellular phenotypes and identify drugs that may protect against diseased phenotypes and deleterious mutations.
MeSH term(s)	Cardiotoxicity/etiology ; Deep Learning ; Drug Evaluation, Preclinical/methods ; Heart/drug effects ; Induced Pluripotent Stem Cells/metabolism ; Myocytes, Cardiac/metabolism
Language	English
Publishing date	2021-08-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.68714
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: AAV9:PKP2 improves heart function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy.

Wu, Iris / Zeng, Aliya / Greer-Short, Amara / Aycinena, J Alex / Tefera, Anley E / Shenwai, Reva / Farshidfar, Farshad / Van Pell, Melissa / Xu, Emma / Reid, Chris / Rodriguez, Neshel / Lim, Beatriz / Chung, Tae Won / Woods, Joseph / Scott, Aquilla / Jones, Samantha / Dee-Hoskins, Cristina / Gutierrez, Carolina G / Madariaga, Jessie /

Robinson, Kevin / Hatter, Yolanda / Butler, Renee / Steltzer, Stephanie / Ho, Jaclyn / Priest, James R / Song, Xiaomei / Jing, Frank / Green, Kristina / Ivey, Kathryn N / Hoey, Timothy / Yang, Jin / Yang, Zhihong Jane

Communications medicine

2024 Volume 4, Issue 1, Page(s) 38

Abstract: Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Currently, there are no approved treatments that address the ... ...

Abstract	Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Currently, there are no approved treatments that address the underlying genetic cause of this disease, representing a significant unmet need. Mutations in Plakophilin-2 (PKP2), encoding a desmosomal protein, account for approximately 40% of ARVC cases and result in reduced gene expression. Methods: Our goal is to examine the feasibility and the efficacy of adeno-associated virus 9 (AAV9)-mediated restoration of PKP2 expression in a cardiac specific knock-out mouse model of Pkp2. Results: We show that a single dose of AAV9:PKP2 gene delivery prevents disease development before the onset of cardiomyopathy and attenuates disease progression after overt cardiomyopathy. Restoration of PKP2 expression leads to a significant extension of lifespan by restoring cellular structures of desmosomes and gap junctions, preventing or halting decline in left ventricular ejection fraction, preventing or reversing dilation of the right ventricle, ameliorating ventricular arrhythmia event frequency and severity, and preventing adverse fibrotic remodeling. RNA sequencing analyses show that restoration of PKP2 expression leads to highly coordinated and durable correction of PKP2-associated transcriptional networks beyond desmosomes, revealing a broad spectrum of biological perturbances behind ARVC disease etiology. Conclusions: We identify fundamental mechanisms of PKP2-associated ARVC beyond disruption of desmosome function. The observed PKP2 dose-function relationship indicates that cardiac-selective AAV9:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations.
Language	English
Publishing date	2024-03-18
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-024-00450-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Author Correction: Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis.

Nature communications

2022 Volume 13, Issue 1, Page(s) 2704

Language	English
Publishing date	2022-05-10
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-30446-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Integrative molecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis.

Nature communications

2022 Volume 13, Issue 1, Page(s) 898

Abstract: Acral melanoma, the most common melanoma subtype among non-White individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we perform integrative genomic and clinical profiling of acral melanomas from 104 ... ...

Abstract	Acral melanoma, the most common melanoma subtype among non-White individuals, is associated with poor prognosis. However, its key molecular drivers remain obscure. Here, we perform integrative genomic and clinical profiling of acral melanomas from 104 patients treated in North America (n = 37) or China (n = 67). We find that recurrent, late-arising focal amplifications of cytoband 22q11.21 are a leading determinant of inferior survival, strongly associated with metastasis, and linked to downregulation of immunomodulatory genes associated with response to immune checkpoint blockade. Unexpectedly, LZTR1 - a known tumor suppressor in other cancers - is a key candidate oncogene in this cytoband. Silencing of LZTR1 in melanoma cell lines causes apoptotic cell death independent of major hotspot mutations or melanoma subtypes. Conversely, overexpression of LZTR1 in normal human melanocytes initiates processes associated with metastasis, including anchorage-independent growth, formation of spheroids, and an increase in MAPK and SRC activities. Our results provide insights into the etiology of acral melanoma and implicate LZTR1 as a key tumor promoter and therapeutic target.
MeSH term(s)	Genomics ; Humans ; Melanoma/pathology ; Oncogenes ; Skin Neoplasms/pathology ; Transcription Factors/genetics ; Melanoma, Cutaneous Malignant
Chemical Substances	LZTR1 protein, human ; Transcription Factors
Language	English
Publishing date	2022-02-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-28566-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito