Skip to Content

148 Results Found

  • Review
  • Open Access
36 Citations
5,420 Views
20 Pages

23 November 2020

Transplantation of neural stem cells (NSCs) has been proposed as an alternative novel therapy to replace damaged neural circuitry after ischemic stroke onset. Nonetheless, albeit the potential of these cells for stroke therapy, many critical challeng...

  • Review
  • Open Access
49 Citations
7,146 Views
18 Pages

Preconditioned and Genetically Modified Stem Cells for Myocardial Infarction Treatment

  • Kamila Raziyeva,
  • Aiganym Smagulova,
  • Yevgeniy Kim,
  • Saltanat Smagul,
  • Ayan Nurkesh and
  • Arman Saparov

2 October 2020

Ischemic heart disease and myocardial infarction remain leading causes of mortality worldwide. Existing myocardial infarction treatments are incapable of fully repairing and regenerating the infarcted myocardium. Stem cell transplantation therapy has...

  • Article
  • Open Access
19 Citations
5,010 Views
13 Pages

Effect of Different Preconditioning Regimens on the Expression Profile of Murine Adipose-Derived Stromal/Stem Cells

  • Patrick C. Baer,
  • Jürgen M. Overath,
  • Anja Urbschat,
  • Ralf Schubert,
  • Benjamin Koch,
  • Asanke A. Bohn and
  • Helmut Geiger

Stem cell-based therapies require cells with a maximum regenerative capacity in order to support regeneration after tissue injury and organ failure. Optimization of this regenerative potential of mesenchymal stromal/stem cells (MSC) or their conditio...

  • Article
  • Open Access
4 Citations
3,431 Views
16 Pages

Hypoxic preconditioning has been demonstrated to increase the resistance of neural stem cells (NSCs) to hypoxic conditions, as well as to improve their capacity for differentiation and neurogenesis. Extracellular vesicles (EVs) have recently emerged...

  • Article
  • Open Access
10 Citations
2,815 Views
23 Pages

30 August 2022

Intravenous adipose mesenchymal stem cells (ADSCs) attenuate renal ischemia/reperfusion (IR) injury but with major drawbacks, including the lack of a specific homing effect after systemic infusion, cell trapping in the lung, and early cell death in t...

  • Article
  • Open Access
1,004 Views
21 Pages

20 November 2025

Hypoxic-ischemic (HI) brain injury is associated with high mortality and severe long-term neurodevelopmental impairments in term newborns. Intranasal mesenchymal stem cell (MSC) therapy is a promising strategy to boost neurorepair after injury, and o...

  • Article
  • Open Access
18 Citations
4,003 Views
16 Pages

Ethionamide Preconditioning Enhances the Proliferation and Migration of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells

  • Na-Hee Lee,
  • Su Hyeon Myeong,
  • Hyo Jin Son,
  • Jung Won Hwang,
  • Na Kyung Lee,
  • Jong Wook Chang and
  • Duk L. Na

23 September 2020

Mesenchymal stem cells (MSCs) are a useful source for cell-based therapy of a variety of immune-mediated diseases, including neurodegenerative disorders. However, poor migration ability and survival rate of MSCs after brain transplantation hinder the...

  • Article
  • Open Access
1 Citations
1,594 Views
15 Pages

Preconditioning with Rapamycin Improves Therapeutic Potential of Placenta-Derived Mesenchymal Stem Cells in Mouse Model of Hematopoietic Acute Radiation Syndrome

  • Vasilii Slautin,
  • Vladislav Ivanov,
  • Alexandr Bugakov,
  • Anna Chernysheva,
  • Ilya Gavrilov,
  • Irina Maklakova,
  • Vladimir Bazarnyi,
  • Dmitry Grebnev and
  • Olga Kovtun

Acute radiation syndrome (ARS) results from high-dose ionizing radiation (IR) exposure, with bone marrow (BM) being highly susceptible due to its proliferative activity. BM injury causes pancytopenia, leading to infections, anemia, and bleeding. Mese...

  • Article
  • Open Access
9 Citations
3,254 Views
14 Pages

14 December 2020

Oxidative stress associated with neuroinflammation is a key process involved in the pathophysiology of neurodegenerative diseases, and therefore, has been proposed as a crucial target for new therapies. Recently, the therapeutic potential of human ad...

  • Review
  • Open Access
30 Citations
6,025 Views
14 Pages

Pre-Conditioning Methods and Novel Approaches with Mesenchymal Stem Cells Therapy in Cardiovascular Disease

  • Anthony Matta,
  • Vanessa Nader,
  • Marine Lebrin,
  • Fabian Gross,
  • Anne-Catherine Prats,
  • Daniel Cussac,
  • Michel Galinier and
  • Jerome Roncalli

12 May 2022

Transplantation of mesenchymal stem cells (MSCs) in the setting of cardiovascular disease, such as heart failure, cardiomyopathy and ischemic heart disease, has been associated with good clinical outcomes in several trials. A reduction in left ventri...

  • Article
  • Open Access
3 Citations
2,648 Views
15 Pages

The Effects of Hypoxic Preconditioned Murine Mesenchymal Stem Cells on Post-Infarct Arrhythmias in the Mouse Model

  • Beschan Ahmad,
  • Anna Skorska,
  • Markus Wolfien,
  • Haval Sadraddin,
  • Heiko Lemcke,
  • Praveen Vasudevan,
  • Olaf Wolkenhauer,
  • Gustav Steinhoff,
  • Robert David and
  • Ralf Gaebel

Ventricular arrhythmias associated with myocardial infarction (MI) have a significant impact on mortality in patients following heart attack. Therefore, targeted reduction of arrhythmia represents a therapeutic approach for the prevention and treatme...

  • Article
  • Open Access
22 Citations
4,126 Views
15 Pages

The preconditioning of mesenchymal stem cells (MSCs) has been recognized as an attractive tool to improve their regenerative and immunomodulatory capacities based on their paracrine effects. In this study, we examined the potential of an MSC-conditio...

  • Article
  • Open Access
7 Citations
3,333 Views
17 Pages

Conditioned Medium from H2O2-Preconditioned Human Adipose-Derived Stem Cells Ameliorates UVB-Induced Damage to Human Dermal Fibroblasts

  • María Burón,
  • Teodoro Palomares,
  • Patricia Garrido-Pascual,
  • Borja Herrero de la Parte,
  • Ignacio García-Alonso and
  • Ana Alonso-Varona

11 October 2022

Human skin exposure to ultraviolet B (UVB) radiation can result in acute photodamage through oxidative modifications of cellular components and biomolecules involved in the metabolism of dermal cells. Recently, the therapeutic potential of human adip...

  • Article
  • Open Access
1,329 Views
27 Pages

Bidirectional Interaction Between PGE2-Preconditioned Mesenchymal Stem Cells and Myofibroblasts Mediates Anti-Fibrotic Effects: A Proteomic Investigation into Equine Endometrial Fibrosis Reversal

  • Lidice Méndez-Pérez,
  • Yat Sen Wong,
  • Belén O. Ibáñez,
  • Ioanna Martinez-Hormaza,
  • Lleretny Rodríguez-Álvarez and
  • Fidel Ovidio Castro

8 September 2025

Background: Endometrosis is a prevalent fibrotic condition in mares that impairs reproductive efficiency by inducing transdifferentiation of endometrial stromal cells into myofibroblasts, leading to excessive ECM deposition. Methods: To elucidate the...

  • Article
  • Open Access
7 Citations
2,530 Views
15 Pages

13 September 2023

Atherosclerosis (AS) is an inflammatory disease involving multiple factors in its initiation and development. In recent years, the potential application of mesenchymal stem cells (MSCs) for treating AS has been investigated. This study examined the e...

  • Article
  • Open Access
26 Citations
4,520 Views
17 Pages

18 December 2019

To confer further therapeutic potential and prevent some adverse effects by the mesenchymal stem cells (MSCs) transplantation, we explored the effects of locally intrarenal arterial administration of hypoxic preconditioned MSCs in the anti-Thy1.1 ind...

  • Article
  • Open Access
2,422 Views
16 Pages

26 April 2025

Hypoxic preconditioning (HP) is a promising approach to enhance the therapeutic efficacy of mesenchymal stem cells (MSCs) by modulating their oxidative stress response, metabolic activity, and secretome composition. Conditioned media (CM) obtained fr...

  • Comment
  • Open Access
4 Citations
3,234 Views
4 Pages

In the recent review published in Brain Sciences, Othman and Tan suggested several preconditioning strategies to improve stem cell therapy after ischemic brain injury [...]

  • Systematic Review
  • Open Access
7 Citations
3,785 Views
25 Pages

16 May 2024

This systematic review aims to gather evidence on the mechanisms triggered by diverse preconditioning strategies for mesenchymal stem cells (MSCs) and their impact on their potential to treat ischemic and traumatic injuries affecting the nervous syst...

  • Review
  • Open Access
3 Citations
4,564 Views
26 Pages

Stroke is one of the leading causes of death and disability worldwide, so there is an urgent need to find a therapy for the tragic outcomes of this cerebrovascular disease. Stem cells appeared to be a good solution for many conditions, so different e...

  • Review
  • Open Access
1,677 Views
35 Pages

Ex Vivo Preconditioning as a Useful Tool for Modification of the Extracellular Matrix of Multipotent Mesenchymal Stromal Cells

  • Elena Andreeva,
  • Olga Zhidkova,
  • Diana Matveeva,
  • Aleksandra Gornostaeva,
  • Margarita Lobanova and
  • Ludmila Buravkova

Cell technologies have provided promising tools for modulating the properties of multipotent mesenchymal stem/stromal cells (MSCs) to meet the needs of cell therapy as well as tissue engineering and regenerative medicine (TERM). Ex vivo preconditioni...

  • Review
  • Open Access
33 Citations
11,972 Views
26 Pages

An Extra Breath of Fresh Air: Hyperbaric Oxygenation as a Stroke Therapeutic

  • Blaise Cozene,
  • Nadia Sadanandan,
  • Bella Gonzales-Portillo,
  • Madeline Saft,
  • Justin Cho,
  • You Jeong Park and
  • Cesar V. Borlongan

4 September 2020

Stroke serves as a life-threatening disease and continues to face many challenges in the development of safe and effective therapeutic options. The use of hyperbaric oxygen therapy (HBOT) demonstrates pre-clinical effectiveness for the treatment of a...

  • Review
  • Open Access
2 Citations
5,115 Views
31 Pages

Therapeutic and Clinical Potential of Adipose-Derived Stem Cell Secretome for Skin Regeneration

  • Anna Sendera,
  • Hubert Kubis,
  • Anna Pałka and
  • Agnieszka Banaś-Ząbczyk

4 November 2025

Adipose-derived stem cells (AT-MSCs) exhibit great potential for application in stem cell therapy, primarily due to their unique pro-regenerative capabilities, which include supporting skin regeneration. AT-MSCs secrete a variety of biomolecules with...

  • Article
  • Open Access
16 Citations
3,197 Views
12 Pages

Proteomic Assessment of Hypoxia-Pre-Conditioned Human Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles Demonstrates Promise in the Treatment of Cardiovascular Disease

  • Cynthia M. Xu,
  • Catherine Karbasiafshar,
  • Rayane Brinck Teixeira,
  • Nagib Ahsan,
  • Giana Blume Corssac,
  • Frank W. Sellke and
  • M. Ruhul Abid

14 January 2023

Human bone marrow mesenchymal stem cell derived-extracellular vesicles (HBMSC-EV) are known for their regenerative and anti-inflammatory effects in animal models of myocardial ischemia. However, it is not known whether the efficacy of the EVs can be...

  • Article
  • Open Access
21 Citations
5,611 Views
12 Pages

21 November 2018

Several studies have demonstrated the beneficial effect of mesenchymal stem cells (MSCs) on intracerebral hemorrhage (ICH). Enhancement of the therapeutic efficacy of MSCs in ICH is necessary, considering the diseases high association with mortality...

  • Article
  • Open Access
1 Citations
1,884 Views
18 Pages

Objective: Secretory factors, termed the secretome, in the conditioned medium (CM) from dental mesenchymal stem cells (MSCs) have shown anti-inflammatory, anti-apoptotic, and tissue regenerative potential. This cell-free product could be further deve...

  • Article
  • Open Access
10 Citations
4,878 Views
17 Pages

The Decellularized Cell-Derived Extracellular Matrix Enhances the Paracrine Function of Human Mesenchymal Stromal/Stem Cells

  • Roman Ushakov,
  • Andrey Ratushnyy,
  • Ludmila Buravkova,
  • Elena Tolkunova and
  • Elena Burova

19 February 2024

The mesenchymal stromal/stem cells (MSCs) are known to secrete pleiotropic paracrine factors, contributing to tissue regeneration. This unique ability makes MSCs promising therapeutic tools for many diseases, including even those that were previously...

  • Review
  • Open Access
1,933 Views
22 Pages

Unlocking MSC Potential: Metabolic Reprogramming via Synthetic Biology Approaches

  • Natalia Trufanova,
  • Oleh Trufanov and
  • Oleksandr Petrenko

17 September 2025

Metabolic engineering of mesenchymal stem/stromal cells (MSCs) represents a compelling frontier for advanced cellular therapies, enabling the precise tuning of their biological outputs. This feature paper examines the critical role of engineered cult...

  • Review
  • Open Access
15 Citations
5,505 Views
30 Pages

Secretome as a Tool to Treat Neurological Conditions: Are We Ready?

  • Andreia Valente da Silva,
  • Inês Serrenho,
  • Beatriz Araújo,
  • Alexandre Martins Carvalho and
  • Graça Baltazar

20 November 2023

Due to their characteristics, mesenchymal stem cells (MSCs) are considered a potential therapy for brain tissue injury or degeneration. Nevertheless, despite the promising results observed, there has been a growing interest in the use of cell-free th...

  • Review
  • Open Access
46 Citations
7,249 Views
20 Pages

Skin flaps are necessary in plastic and reconstructive surgery for the removal of skin cancer, wounds, and ulcers. A skin flap is a portion of skin with its own blood supply that is partially separated from its original position and moved from one pl...

  • Review
  • Open Access
383 Views
30 Pages

Characterization, Preconditioning, Safety, and Other Issues of MSC-Derived EVs and Secretome

  • Elena V. Alpeeva,
  • Anfisa S. Ryabchenko and
  • Ekaterina A. Vorotelyak

9 February 2026

Recently, a growing number of scientific research and clinical studies have demonstrated the potential of extracellular vesicles (EVs) secreted by cells of different types for treating various diseases. It was shown that most frequently, substances a...

  • Article
  • Open Access
6 Citations
6,856 Views
28 Pages

The Immunoregulatory and Regenerative Potential of Activated Human Stem Cell Secretome Mitigates Acute-on-Chronic Liver Failure in a Rat Model

  • Barbara Cuadra,
  • Veronica Silva,
  • Ya-Lin Huang,
  • Yael Diaz,
  • Claudio Rivas,
  • Cristobal Molina,
  • Valeska Simon,
  • Maria Rosa Bono,
  • Bernardo Morales and
  • Marcelo Ezquer
  • + 4 authors

8 February 2024

Acute-on-chronic liver failure (ACLF) is a syndrome marked by sudden liver function decline and multiorgan failure, predominantly acute kidney injury (AKY), in patients with chronic liver disease. Unregulated inflammation is a hallmark of ACLF; howev...

  • Article
  • Open Access
3 Citations
2,590 Views
25 Pages

Preconditioned Chorionic Villus Mesenchymal Stem/Stromal Cells (CVMSCs) Minimize the Invasive Phenotypes of Breast Cancer Cell Line MDA231 In Vitro

  • Abdullah Al Subayyil,
  • Yasser S. Basmaeil,
  • Hayaa Bin Kulayb,
  • Maha Alrodayyan,
  • Lama Abdulaziz A. Alhaber,
  • Taghreed N. Almanaa and
  • Tanvir Khatlani

Among the newer choices of targeted therapies against cancer, stem cell therapy is gaining importance because of their antitumor properties. Stem cells suppress growth, metastasis, and angiogenesis, and induce apoptosis in cancer cells. In this study...

  • Article
  • Open Access
12 Citations
3,392 Views
15 Pages

Characterization of Extracellular Vesicles from Preconditioned Human Adipose-Derived Stromal/Stem Cells

  • Alec Geßner,
  • Benjamin Koch,
  • Kevin Klann,
  • Dominik C. Fuhrmann,
  • Samira Farmand,
  • Ralf Schubert,
  • Christian Münch,
  • Helmut Geiger and
  • Patrick C. Baer

Cell-free therapy using extracellular vesicles (EVs) from adipose-derived mesenchymal stromal/stem cells (ASCs) seems to be a safe and effective therapeutic option to support tissue and organ regeneration. The application of EVs requires particles wi...

  • Article
  • Open Access
8 Citations
4,878 Views
11 Pages

1 February 2021

Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has b...

  • Article
  • Open Access
64 Citations
7,515 Views
15 Pages

3 December 2018

Periodontitis is a common disease characterized by chronic inflammation and tissue destruction of gums. Human periodontal ligament stem cells (PDLSCs), derived from the periodontium, have stem cell properties similar to those of mesenchymal stem cell...

  • Article
  • Open Access
133 Citations
9,028 Views
14 Pages

Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survi...

  • Article
  • Open Access
2,164 Views
31 Pages

Study of the Therapeutic Effect of Cytokine-Preconditioned Mesenchymal Stem Cells and Their Exosomes in a Mouse Model of Psoriasis

  • Aidar Dairov,
  • Assel Issabekova,
  • Madina Sarsenova,
  • Aliya Sekenova,
  • Miras Shakhatbayev,
  • Symbat Alimbek,
  • Gulshakhar Kudaibergen,
  • Assiya Nurkina,
  • Ilyas Akhmetollayev and
  • Vyacheslav Ogay
  • + 1 author

11 August 2025

Mesenchymal stem cells (MSCs) are a type of multipotent, non-hematopoietic cells of mesodermal origin. Due to their strong immunomodulatory, immunosuppressive, and regenerative potential, MSCs are used in cell therapy for inflammatory, immune-mediate...

  • Article
  • Open Access
64 Citations
6,090 Views
14 Pages

16 February 2022

In the past decade, mesenchymal stem cells (MSCs) have been widely used for the treatment of osteoarthritis (OA), and extracellular vesicles (EVs) may play a major role in the efficacy of this treatment. Hypoxia can change the cargo and biological fu...

  • Article
  • Open Access
8 Citations
4,573 Views
17 Pages

Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis

  • Rachel M. Wise,
  • Mark A. A. Harrison,
  • Brianne N. Sullivan,
  • Sara Al-Ghadban,
  • Sarah J. Aleman,
  • Amber T. Vinluan,
  • Emily R. Monaco,
  • Umberto M. Donato,
  • India A. Pursell and
  • Bruce A. Bunnell

30 September 2020

Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-d...

  • Article
  • Open Access
8 Citations
3,932 Views
16 Pages

Short-Term Autophagy Preconditioning Upregulates the Expression of COX2 and PGE2 and Alters the Immune Phenotype of Human Adipose-Derived Stem Cells In Vitro

  • Rachel M. Wise,
  • Sara Al-Ghadban,
  • Mark A. A. Harrison,
  • Brianne N. Sullivan,
  • Emily R. Monaco,
  • Sarah J. Aleman,
  • Umberto M. Donato and
  • Bruce A. Bunnell

19 April 2022

Human adipose-derived stem cells (hASCs) are potent modulators of inflammation and promising candidates for the treatment of inflammatory and autoimmune diseases. Strategies to improve hASC survival and immunoregulation are active areas of investigat...

  • Article
  • Open Access
70 Citations
5,466 Views
16 Pages

18 April 2019

The aim of this study was to determine the optimal preconditioning regimen for the wound healing therapeutic efficacy of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). To this end, we compared various preconditioning regimens for b...

  • Article
  • Open Access
17 Citations
3,629 Views
12 Pages

Thrombin Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage Induced Neonatal Rats

  • So Yeon Jung,
  • Young Eun Kim,
  • Won Soon Park,
  • So Yoon Ahn,
  • Dong Kyung Sung,
  • Se In Sung,
  • Kyeung Min Joo,
  • Seong Gi Kim and
  • Yun Sil Chang

Severe intraventricular hemorrhage (IVH) remains a major cause of high mortality and morbidity in extremely preterm infants. Mesenchymal stem cell (MSC) transplantation is a possible therapeutic option, and development of therapeutics with enhanced e...

  • Article
  • Open Access
1 Citations
1,484 Views
15 Pages

Exosomes Derived from Mg-Preconditioned Bone Mesenchymal Stem Cells Promote Angiogenesis and Osteogenesis for Osteonecrosis Treatment

  • Long Li,
  • Luyao Cheng,
  • Yuhan Du,
  • Yuyang Zhang,
  • Zetao Wang,
  • Yangyi Nie,
  • Jing Long,
  • Cairong Li,
  • Yuanchi Zhang and
  • Wei Zhang
  • + 1 author

13 October 2025

Steroid-induced osteonecrosis of the femoral head (SONFH) is a common and refractory orthopedic disorder, often resulting from prolonged or high-dose glucocorticoid use that impairs bone repair and vascularization. The critical impact of exosomes der...

  • Article
  • Open Access
32 Citations
5,597 Views
15 Pages

We investigated whether thrombin preconditioning of human Wharton’s jelly–derived mesenchymal stem cells (MSCs) improves paracrine potency and thus the therapeutic efficacy of naïve MSCs against severe hypoxic ischemic encephalopathy...

  • Article
  • Open Access
39 Citations
4,538 Views
13 Pages

We investigated the role of protease-activated receptor (PAR)-mediated signaling pathways in the biogenesis of human umbilical cord blood-derived mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) and the enrichment of their cargo conte...

  • Article
  • Open Access
15 Citations
3,641 Views
26 Pages

Osteogenic Potential of Sheep Mesenchymal Stem Cells Preconditioned with BMP-2 and FGF-2 and Seeded on an nHAP-Coated PCL/HAP/β-TCP Scaffold

  • Sandra Stamnitz,
  • Agnieszka Krawczenko,
  • Urszula Szałaj,
  • Żaneta Górecka,
  • Agnieszka Antończyk,
  • Zdzisław Kiełbowicz,
  • Wojciech Święszkowski,
  • Witold Łojkowski and
  • Aleksandra Klimczak

31 October 2022

Mesenchymal stem cells (MSCs) attract interest in regenerative medicine for their potential application in bone regeneration. However, direct transplantation of cells into damaged tissue is not efficient enough to regenerate large bone defects. This...

  • Article
  • Open Access
33 Citations
4,414 Views
15 Pages

26 April 2020

Mesenchymal stem cells (MSCs) have considerable therapeutic abilities in various disorders, including hepatic fibrosis. They may be affected with different culture conditions. This study investigated, on molecular basics, the effect of pretreatment w...

  • Article
  • Open Access
14 Citations
3,995 Views
16 Pages

Effect of Hypoxia Preconditioned Secretomes on Lymphangiogenic and Angiogenic Sprouting: An in Vitro Analysis

  • Philipp Moog,
  • Rahmin Schams,
  • Alexander Schneidinger,
  • Arndt F. Schilling,
  • Hans-Günther Machens,
  • Ektoras Hadjipanayi and
  • Ulf Dornseifer

Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are two blood-derived autologous growth factor compositions that are being clinically employed as tools for promoting tissue regeneration, and have been extensively examined for their angiogenic act...

  • Article
  • Open Access
14 Citations
5,168 Views
17 Pages

17 October 2018

A combinatorial approach integrating stem cells and capable of exploiting available cues is likely needed to regenerate lost neural tissues and ultimately restore neurologic functions. This study investigates the effects of the subcutaneous maturatio...

of 3