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The Management of Patients with Heart Failure and Diabetes
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
The dipeptidyl peptidase-4 (DPP-4) inhibitors, saxagliptin and alogliptin, have been associated with an increased risk of HF hospitalizations, prompting a statement from the Food and Drug Administration.74–77 The American Heart Association issued a scientific statement stating that saxagliptin may worsen myocardial dysfunction.78 Although DPP-4 inhibitors increase GLP-1, they also increase the expression of stromal cell-derived factor-1, leading to cardiac fibrosis.79
Breast Cancer Stem Cells and Their Niche: Lethal Seeds in Lethal Soil
Published in Brian Leyland-Jones, Pharmacogenetics of Breast Cancer, 2020
Danuta Balicki, Brian Leyland-Jones, Max S. Wicha
Activated, irradiated, mammary fibroblasts are critical to the microenvironment of mammary stem cells as they are required for the successful repopulation of cleared mammary fat pads in immunocompromised mice (102). These epithelial-stromal interactions are also important in malignant transformation and likely to be important with cancer stem cells (11). Fibroblasts secrete matrix metalloproteinases and protease inhibitors and mobilize and activate growth factors such as tumor growth factor-β (TGF-β), which has been shown to promote tumor progression and invasion (103). Carcinoma-associated fibroblasts promote angiogenesis, as well as tumor growth, by secreting stromal cell-derived factor-1 (SDF-1), which interacts with the chemokine receptor CXCR4 on tumor cells and endothelial cells (104). As radiographic breast density correlates with increased breast cancer risk, as well as increased fibroblasts and collagen deposition, this modified niche may promote the transformation of initiated stem cells into cancer stem cells (11,105).
Regulation of fertility and infertility in humans
Published in C. Yan Cheng, Spermatogenesis, 2018
Nahid Punjani, Ryan Flannigan, Peter N. Schlegel
During embryologic development, PGCs arise from the extraembryonic tissues adjacent to the yolk sac. Migration to the gonadal ridge occurs at 3 to 5 weeks, and differentiation to gonocytes occurs via inducible factors mediated by Sertoli cells (SCs).18,19 Gonocytes remain mitotically inactive until birth, where they differentiate into spermatogonia (SPG) within the seminiferous tubules over the following 6 months. This is mediated by a number of factors, including stromal cell derived factor 1 (SDF-1), activator protein-2 (AP-2), stem cell factor (SCF), growth and differentiation factor 3 (GDF3), retinoic acid, estradiol, and DNA methylation changes.20–29 SPGs remain quiescent until 5–7 years of age, where proliferation occurs followed by a combination of proliferation and differentiation during puberty with the onset of spermatogenesis.30,31
Drug loaded implantable devices to treat cardiovascular disease
Published in Expert Opinion on Drug Delivery, 2023
Masoud Adhami, Niamh K. Martin, Ciara Maguire, Aaron J. Courtenay, Ryan F. Donnelly, Juan Domínguez-Robles, Eneko Larrañeta
Growth factors, extracellular vesicles, and microRNAs are some examples of bioactive molecules loaded in these acellular cardiac patches. Growth factors are naturally occurring bioactive molecules that affect the growth of cells, for example, stimulating cell proliferation or cellular differentiation [122]. For instance, a combination of both growth factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were loaded in fibrous scaffolds made from poly(l-lactide-co-caprolactone) (PLCL) and poly(2-ethyl-2-oxazoline) (PEOz) by using electrospinning [123]. The results of this study indicated that cells were able to respond at a molecular level by using the growth factors-loaded scaffolds, which also helped to reduce scar tissue formation [123]. In a different work, the authors manufactured a cardiac patch comprising an electronic mesh including multiple electrodes for different purposes, such as cell and tissue electrical stimulation in combination with the sustained release of bioactive molecules within the cardiac tissue [124]. In this study, stromal cell-derived factor-1 (SDF-1) was released from the performed cardiac patch, which was able to stimulate in vitro cell migration. Furthermore, the release of SDF-1 could promote better vascularization [124].
Novel therapeutic perspectives for crescentic glomerulonephritis through targeting parietal epithelial cell activation and proliferation
Published in Expert Opinion on Therapeutic Targets, 2023
Yanjie Huang, Xueru Zhao, Qiushuang Zhang, Xiaoqing Yang, Gailing Hou, Chaoqun Peng, Mengzhen Jia, Li Zhou, Tatsuo Yamamoto, Jian Zheng
In CrGN, glomerular injury can increase the permeability of the glomerular capillary basement membrane. The infiltrating inflammatory cells, soluble cytokines, and chemokines entered the Bowman’s space, triggering PECs to express adhesion molecules and chemokine receptors (such as C-X-C chemokine receptor 4 (CXCR4)) [10]. Simultaneously, monocytes or macrophages induce an increase in local angiotensin II (AngII) production. AngII activates podocytes to produce stromal cell-derived factor-1 (SDF-1) by binding to angiotensin II type 1 receptor (AT1R). SDF-1 binds to its receptor, CXCR4, which is involved in the activation of PECs in the CrGN [7,10]. In 2019, Nanako et al. showed that in an inflammatory state, CXCR4 binding to SDF-1 led to a change in the chemotactic conformation of CXCR4, which induced the activation of the Ras-Raf-mitogen-activated protein kinase and ERK pathways by the Src tyrosine kinase family (Figure 2) [63]. AngII not only participates in PEC activation through binding of SDF-1 and CXCR4 but also directly affects the activation and proliferation of PECs [64]. In the progressive glomerular injury rat model, AngII induced mitosis in PECs by decreasing the transcription factor C/EBPδ, a cell cycle inhibitor, and eventually led to the activation and proliferation of PECs. Lisinopril, an ACE inhibitor (ACEI), up-regulated the activation of C/EBPδ and inhibited the proliferation and migration of PECs (Figure 2) [65]. Therefore, these findings indicate that PECs are novel cellular targets for ACEI and AT1 receptor blocker (ARB) therapies (Table 1) [66–68].
Current status of drug repositioning in hematology
Published in Expert Review of Hematology, 2021
Although plerixafor was initially investigated as an anti-human immunodeficiency virus (HIV) agent, its clinical development was stopped owing to insufficient efficacy. The action mechanism is the inhibition of CXCL12 binding to CXCR4 as one of the HIV-1 coreceptors [14]. CXCR4, a cognate receptor of stromal cell-derived factor 1 (SDF1/CXCL12), has regulatory roles in CD34+ hematopoietic progenitor cell trafficking [15]. Based on this finding, it has been revealed that plerixafor mobilizes CD34+ and hematopoietic progenitor cells from the bone marrow to peripheral blood [16]. DiPersio et al. conducted a phase III trial comparing plerixafor plus granulocyte colony-stimulating factor (G-CSF) mobilization to placebo plus G-CSF mobilization in patients with non-Hodgkin lymphoma who underwent ASCT [17]. They reported that the percentage of patients for whom at least 5 × 106 CD34+ cells/kg were collected in four or fewer apheresis days was higher in the former group (59% vs. 20%, P < 0 · 001). According to another phase III trial comparing plerixafor/G-CSF and placebo/G-CSF, the percentage of patients with at least 6 × 106 CD34+ cells/kg in two or fewer apheresis sessions was higher in the former group (72% vs. 34%, P < 0 · 001) [18]. Plerixafor was approved by the FDA and European Medicines Agency (EMEA) for ASCT in patients with lymphoma or MM in 2008 and 2009, respectively.