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Disease Prediction and Drug Development
Published in Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam, Introduction to Computational Health Informatics, 2019
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam
The human-body has many types of cell signaling pathways such as: 1) cell-growth; 2) programmed cell-death; 3) cytoskeleton and extracellular matrix; 4) disease drivers, EMT (Epithelial-Mesenchymal Transition for wound healing) and angiogenesis (generation of blood-vessels); 5) epigenetics (changes in the organism due to gene-expression variations); 6) immune cell signaling and 7) neurodegenerative signaling.
JAK-STAT pathway: Testicular development, spermatogenesis and fertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Ligand molecules are the extracellular molecules that cannot cross the membrane but through ligand-receptor interaction have the potential to activate an intracellular cell signaling cascade. Initially, the JAK-STAT pathway was discovered by interferon (IFN)-induced intracellular signaling. But later, a large number of cytokines, interferons and growth hormones were known to induce JAK-STAT signaling. In mammals, these ligand molecules are classified into various families depending on their structural and functional characteristics (10) (Table 15.3). In Drosophila, Upd is the only known ligand molecule for inducing JAK-STAT signaling. The unpaired gene encodes a 47 kDa secretory glycoprotein, localized to an extracellular matrix (ECM) (16). While curating a Drosophila database, other Upd-like genes have also been identified, such as Upd2 (19) and Upd3 (17).
Protein Function As Cell Surface And Nuclear Receptor In Human Diseases
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Urmila Jarouliya, Raj K. Keservani
As discussed above, several cell surface and nuclear receptor that are constituted of proteins have a major role in cell signaling for the transcription of the function genes involved in the various cellular activity. Over-expression or misfunctioning of these receptors causes various diseases in human beings. For the therapeutic purpose, these receptors and their target ligand is the major area of scientific study.
C1q-like 1 is frequently up-regulated in lung adenocarcinoma and contributes to the proliferation and invasion of tumor cells
Published in Journal of Chemotherapy, 2021
Yu-Jun Gao, Feng Chen, Lian-Jun Zhang
All protein expression levels were analyzed by Western blotting analysis. Briefly, protein extraction was executed in RIPA lysis buffer supplemented with protease inhibitor (Roche). Moreover, about 20 µg protein sample was resolved by SDS–PAGE, and then transferred onto a PVDF membrane. After being blocked with 5% defatted milk, the membrane was incubated with primary antibodies for all night at 4 °C and then incubated with secondary antibodies at room temperature for 1 h. Finally, the membrane was visualized by an ECL detection (GE Healthcare). GAPDH was utilized as an internal control. The primary antibodies used in the present study were as follows: C1QL1 (1:1000, ab68528, Abcam), E-cadherin (1:1000, #14472, Cell Signaling Technology (CST), Inc.), N-cadherin (1:1000, #13116, CST), Vimentin (1:1000, #5741, CST), Snail (1:1000, #3879, CST), GAPDH (1:5000, #5174, CST). And the secondary antibodies (1:5000, #7076 and #7074) were obtained from Cell Signaling Technology, Inc.
Effects of hepatocyte growth factor gene-transfected mesenchymal stem cells on dimethylnitrosamine-induced liver fibrosis in rats
Published in Growth Factors, 2019
Soung Hoon Moon, Chang Min Lee, See-Hyoung Park, Myeong Jin Nam
To measure the difference in protein expression between control and H2O2-treated MSCs, 4 × 106 cells were harvested and lysed in a lysis buffer containing 7 M urea and 2 M thiourea with protease inhibitor (Sigma-Aldrich) and phenylmethyl-sulfonyl fluoride (Sigma-Aldrich). The concentration of extracted proteins was determined using a Qubit Flourocytometer (Invitrogen) by loading equal amounts of protein onto each well of the NuPAGE Bis-Tris Gel (Invitrogen). Protein samples were separated using sodium dodecyl-sulfate polyacrylamide gel electrophoresis at 200 V for 1 h and then transferred electrophoretically to a nitrocellulose membrane at 50 V for 2 h. The transferred membranes were blocked by bovine serum albumin (Santa Cruz, CA, USA) and incubated with primary antibody at 4 °C overnight. Secondary antibodies were purchased from Cell Signaling Technology. The membranes were washed again and detected using the Chemi Doc MP imaging system (Bio-Rad, Hercules, CA, USA).
Improving cellular uptake of therapeutic entities through interaction with components of cell membrane
Published in Drug Delivery, 2019
Renshuai Zhang, Xiaofei Qin, Fandong Kong, Pengwei Chen, Guojun Pan
Proteins are the second major components of cell membranes and some of them can mediate cellular uptake termed also receptor-mediated uptake in general describing. In order to profound the understanding of key role of trans-membrane proteins in mediated drug delivery, they were divided into two categories, transporters and receptors in this review. For instance, some trans-membrane proteins are transporters that carry small molecules (e.g. glucose) into the cell. Some other proteins are known as receptors to mediate the cell signaling pathway for growth and proliferation. For transporters, they maintained the normal metabolism of cells via transferring necessary nutrients from the outside to the inside. Meanwhile, some transporters showed high affinity to ligand-drug conjugates and even ligand-drug carrier complexes. Thus, it provided an ideal opportunity for enhancing drug delivery and improving drug targeting. For receptors, they can be especially bound by natural ligands or monoclonal antibodies (mAbs), and thus mediated cellular signal or used in the treatment of disease. To date, lots of mAbs have been conjugated to small molecule drugs or drug carriers for drug delivery. Additionally, some transporters can also be targeted by mAbs, such as folate receptors (FR) which transport folate into cells, and meanwhile as antigens can specially bind anti-FR antibody. Importantly, covalent attachment of small molecule drugs or drug carriers to antibodies did not significantly influence their cell internalization, thus providing another delivery strategy utilizing interaction between antibody and membrane proteins.