Abstract:<b><i>Background:</i></b> Chronic kidney disease (CKD) has become a global public health problem nowadays. As cardiovascular diseases (CVDs) are the primary cause of death in advanced CKD patients, much attention has been paid to resolving their cardiovascular complications. However, managing CKD and cardiovascular complications is still a big challenge for nephrologists, as satisfactory treatments are still lacking. Platelets, the second most abundant cells in the blood, are the major … Show more
“…Previous studies have shown that PMPs transfer their genetic contents, such as miRNAs, to target cells and affect gene expression in vitro [15][16][17][18][19][20][21][22]. In our study, we found that the molecular ndings were consistent with the results of reduced cell proliferation in cell culture.…”
BackgroundThe current understanding emphasizes the intricate interplay between leukemia and its environment. Platelet microparticles play a crucial role in facilitating intercellular communication and contribute to the complex landscape of cancer pathology. This study aimed to investigate the in uence of Platelet microparticles on cell proliferation, apoptosis, and the expression of key genes, including P53, P21, Cyclin D1, Bax, and Bcl-2, within the context of a Chronic Myeloid Leukemia cell line (K562).
Methods and ResultsPlatelet microparticles were obtained through centrifugation at various speeds, and their concentration was quanti ed using the BCA assay. To determine the size and immunophenotypic characteristics of the PMPs, both the DLS technique and ow cytometry were employed. Cell proliferation was assessed using the MTT assay, and cell cycle analysis was conducted through DNA content evaluation. Real-time PCR was utilized for gene expression analysis of Bax, Bcl-2, Cyclin D1, P53, and P21. Flow cytometry was employed to examine cell apoptosis. The ndings revealed that platelet microparticles have the ability to decrease proliferation of the K562 cell line, while not exerting an impact on apoptosis and cell cycle progression. Analysis through real-time PCR indicated an upregulation in the gene expression of P53, P21, and Bcl-2, accompanied by a downregulation in Bax and Cyclin D1.
ConclusionThis investigation sheds light on the intricate relationship between CML and its microenvironment, particularly the involvement of platelet-derived microparticles. The study underscores the potential of PMPs to in uence cell behavior and gene expression, providing a deeper understanding of their role in CML and its therapeutic implications.
“…Previous studies have shown that PMPs transfer their genetic contents, such as miRNAs, to target cells and affect gene expression in vitro [15][16][17][18][19][20][21][22]. In our study, we found that the molecular ndings were consistent with the results of reduced cell proliferation in cell culture.…”
BackgroundThe current understanding emphasizes the intricate interplay between leukemia and its environment. Platelet microparticles play a crucial role in facilitating intercellular communication and contribute to the complex landscape of cancer pathology. This study aimed to investigate the in uence of Platelet microparticles on cell proliferation, apoptosis, and the expression of key genes, including P53, P21, Cyclin D1, Bax, and Bcl-2, within the context of a Chronic Myeloid Leukemia cell line (K562).
Methods and ResultsPlatelet microparticles were obtained through centrifugation at various speeds, and their concentration was quanti ed using the BCA assay. To determine the size and immunophenotypic characteristics of the PMPs, both the DLS technique and ow cytometry were employed. Cell proliferation was assessed using the MTT assay, and cell cycle analysis was conducted through DNA content evaluation. Real-time PCR was utilized for gene expression analysis of Bax, Bcl-2, Cyclin D1, P53, and P21. Flow cytometry was employed to examine cell apoptosis. The ndings revealed that platelet microparticles have the ability to decrease proliferation of the K562 cell line, while not exerting an impact on apoptosis and cell cycle progression. Analysis through real-time PCR indicated an upregulation in the gene expression of P53, P21, and Bcl-2, accompanied by a downregulation in Bax and Cyclin D1.
ConclusionThis investigation sheds light on the intricate relationship between CML and its microenvironment, particularly the involvement of platelet-derived microparticles. The study underscores the potential of PMPs to in uence cell behavior and gene expression, providing a deeper understanding of their role in CML and its therapeutic implications.
“…Uremic toxin accumulation leads to increased oxidative stress, 11 inflammation, 12 , 13 and increased platelet dysfunction, 14 , 15 , 16 whereas phosphate retention contributes to vascular calcification 17 and parathyroid mediated bone problems ( Figure 1 ). 18 , 19 In this section, we will limit our discussion to novel mechanisms pertaining to inflammation and platelet-related pathophysiology in CKD because other mechanisms were extensively reviewed by others, 10 , 20 , 21 , 22 , 23 , 24 and managing immune cells and inflammation is an active area of research that would potentially generate new therapies for CKD management. Figure 1 Mechanisms for excessive CV events in patients with CKD arising from reduced excretion from the kidney or reduced hormone (erythropoietin and calcitriol) production from the kidney.…”
“…Thus, blocking the generation and release of EVs was found to reduce blood pressure in hypertensive rats [ 203 ]. Furthermore, an increase in circulatory EC-EV levels has been found in patients with endothelial dysfunction [ 204 ], obstructive sleep apnea [ 205 ], obesity [ 206 , 207 ], renal failure [ 208 ], coronary artery disease [ 209 ], myocardial infarction [ 210 , 211 , 212 ], β-thalassemia [ 213 ], and stroke [ 214 ]. Nevertheless, it is not clear if the increase in their number contributes to these conditions.…”
Section: Biology Of Extracellular Vesiclesmentioning
Extracellular vesicles (EVs) are nanoparticles released from various cell types that have emerged as powerful new therapeutic option for a variety of diseases. EVs are involved in the transmission of biological signals between cells and in the regulation of a variety of biological processes, highlighting them as potential novel targets/platforms for therapeutics intervention and/or delivery. Therefore, it is necessary to investigate new aspects of EVs’ biogenesis, biodistribution, metabolism, and excretion as well as safety/compatibility of both unmodified and engineered EVs upon administration in different pharmaceutical dosage forms and delivery systems. In this review, we summarize the current knowledge of essential physiological and pathological roles of EVs in different organs and organ systems. We provide an overview regarding application of EVs as therapeutic targets, therapeutics, and drug delivery platforms. We also explore various approaches implemented over the years to improve the dosage of specific EV products for different administration routes.
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