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Commissioning Services
Published in Cathy Laver-Bradbury, Margaret J.J. Thompson, Christopher Gale, Christine M. Hooper, Child and Adolescent Mental Health, 2021
Pathway analysis is a helpful approach for understanding users’ experiences of life or services and highlighting where the most efficient and effective points are for identifying and addressing needs and moving resources. This will help to identify the strategy for early intervention or prevention.
Experimental Protocols for Generation and Evaluation of Articular Cartilage
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
The pathway analysis paradigm includes several steps: applying a stimulus, determining a measurable output, detecting changes in the signaling of target pathway components (usually changes in phosphorylation), and then altering that signaling via inhibition or activation (commonly by pharmacological means) to determine changes in the previously determined output. Through systematic probing, it can be determined if pathway components are sufficient or necessary for a specific stimulus to result in a specific output.
Targeted and Untargeted Metabolomics for Specific Food Intake Assessment
Published in Dale A. Schoeller, Margriet S. Westerterp-Plantenga, Advances in the Assessment of Dietary Intake, 2017
Carl Brunius, Huaxing Wu, Rikard Landberg
We set up an explorative study using untargeted metabolomics and developed an algorithm to discover whole grain rye intake biomarkers as an example. Using that approach, previously known molecules specifically reflecting rye consumption were identified as tentative biomarkers as well as other, not previously associated with rye, showing the great potential of untargeted metabolomics for biomarker discovery as well as other biological applications. With main focus on biostatistics, we have illustrated that studies incorporating metabolomics need to consider and accurately address the entire workflow from experimental design to identification and interpretation. To avoid overfitting and false-positive findings, both prudent within-model statistical validation and permutation analysis are required. These issues were exemplified in detail by the effects of variable selection filters and modeling method on statistical validation performance, variable ranking and final selection for identification, which is an extremely complicated and time consuming task and, in fact, one of the main bottlenecks in metabolomics. Biological interpretation through pathway analysis was not performed in our case, and should otherwise be used with caution, only if allowed through experimental design and methodological choices.
TYK2 as a novel therapeutic target in psoriasis
Published in Expert Review of Clinical Pharmacology, 2023
Sarah Elyoussfi, Shraddha S Rane, Steve Eyre, Richard B Warren
The TYK2 inhibitor deucravacitinib shows significant promise as an effective, potentially long term, oral agent for treating psoriasis to date. It appears that other molecules, also trying to target TYK2 specifically, are struggling to achieve the same advantages deucravacitinib has over the traditional JAK inhibitors. However, TYK2 blockade orally does not achieve the same levels of response of the highest performing injectable therapies, and longer-term data are needed to know if the thrombotic risk and cancer risk are distinct from the JAK inhibitors used for treating other inflammatory conditions. Thus, efforts to optimize the right patient 1st time for this given drug are critical. Pathway analysis by genetic and genomic means will be important in the coming years, especially to ensure the success of drugs that have achieved moderate to high levels of efficacy. Psoriasis is a complex genetic disease for which risk is influenced by both genes and environmental factors. GWAS studies have identified a number of regions of DNA with increased risk of disease.
Mechanism of lily bulb and Rehmannia decoction in the treatment of lipopolysaccharide-induced depression-like rats based on metabolomics study and network pharmacology
Published in Pharmaceutical Biology, 2022
Xiansu Chi, Xiaoyan Xue, Jin Pan, Jiang Wu, Huishan Shi, Yong Wang, Yanting Lu, Zhe Zhang, Ke Ma
In this study, we identified several pathways that may be perturbed in LPS-induced depression-like rats. The 20 most significantly different pathways are as follows: (1) neurotrophin signalling pathway; (2) Kaposi sarcoma-associated herpesvirus infection; (3) gonadotropin-releasing hormone (GnRH) signalling pathway; (4) adipocytokine signalling pathway; (5) Fc gamma R-mediated phagocytosis; (6) advanced glycation end product (AGE)-receptor for AGE (RAGE) signalling pathway in diabetic complications; (7) choline metabolism in cancer; (8) phospholipase D signalling pathway; (9) fat digestion and absorption; (10) sphingolipid signalling pathway; (11) retrograde endocannabinoid signalling; (12) insulin resistance; (13) pathways in cancer; (14) cAMP signalling pathway; (15) glycerophospholipid metabolism; (16) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance; (17) pancreatic cancer; (18) NF-κB signalling pathway; (19) T-helper type 1 (Th1) and T-helper type 2 (Th2) cell differentiation cell differentiation; and (20) glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The detailed results of pathway analysis are shown in Figure 6(C).
Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells: II. Signal Transduction Pathways Involved
Published in Nutrition and Cancer, 2021
Ergül Mutlu Altundağ, Ayşe Mine Yılmaz, Belgin Sert Serdar, Ayşe Tarbın Jannuzzi, Semra Koçtürk, A. Süha Yalçın
Human Signal Transduction Pathway Finder-RT2 PCR Array system (CFX Connect Real Time Detection System, Bio-Rad) was used in investigating various signaling pathways. For each reaction, 5 μg of total RNA was extracted and then submitted to reverse transcription. cDNA synthesis was carried out using the first strand cDNA synthesis kit (iScript™, Bio-Rad). The resulting cDNA was added to the RT2 Real-Time™ SYBR Green/ROX PCR master that contained real-time PCR buffer, a high-performance HotStart DNA Taq polymerase, nucleotides, SYBR Green dye, and the ROX reference dye. Aliquots of the mixture were placed into each well of a 96-well plate that included primer sets for specific genes plus housekeeping genes. Real-time PCR was performed with CFX Real Time PCR Detection System (Bio-Rad). Analysis was based on the ΔΔCt method with normalization of raw data to the average of five housekeeping genes. Data was represented as fold regulation of treatment groups divided by their controls. To analyze and visualize the results of microarray experiments DAVID v6.8, which is a well-known function/annotation method, was used. Also, KEGG pathway database was used for pathway analysis.