scholarly journals Role of intracellular poroelasticity on freezing-induced deformation of cells in engineered tissues

2016 ◽  
Vol 13 (123) ◽  
pp. 20160480
Author(s):  
Soham Ghosh ◽  
Altug Ozcelikkale ◽  
J. Craig Dutton ◽  
Bumsoo Han
Keyword(s):  
Water Transport ◽  
Biomedical Applications ◽  
Biological Tissues ◽  
Cell Dehydration ◽  
Spatio Temporal ◽  
Cellular Water ◽  
Induced Changes ◽  
Cellular Water Transport ◽  
Insight Into

Freezing of biomaterials is important in a wide variety of biomedical applications, including cryopreservation and cryosurgeries. For the success of these applications to various biomaterials, biophysical mechanisms, which determine freezing-induced changes in cells and tissues, need to be well understood. Specifically, the significance of the intracellular mechanics during freezing is not well understood. Thus, we hypothesize that cells interact during freezing with the surroundings such as suspension media and the extracellular matrix (ECM) via two distinct but related mechanisms—water transport and cytoskeletal mechanics. The underlying rationale is that the cytoplasm of the cells has poroelastic nature, which can regulate both cellular water transport and cytoskeletal mechanics. A poroelasticity-based cell dehydration model is developed and confirmed to provide insight into the effects of the hydraulic conductivity and stiffness of the cytoplasm on the dehydration of cells in suspension during freezing. We further investigated the effect of the cytoskeletal structures on the cryoresponse of cells embedded in the ECM by measuring the spatio-temporal intracellular deformation with dermal equivalent as a model tissue. The freezing-induced change in cell, nucleus and cytoplasm volume was quantified, and the possible mechanism of the volumetric change was proposed. The results are discussed considering the hierarchical poroelasticity of biological tissues.

Role of enkephalins in regulation of basal intestinal water and ion absorption in the rat

1984 ◽  
Vol 246 (4) ◽  
pp. G386-G392
Author(s):  
R. Fogel ◽  
R. B. Kaplan
Keyword(s):  
Receptor Antagonist ◽  
Water Transport ◽  
Opiate Receptor ◽  
Ion Absorption ◽  
Mu Receptors ◽  
Induced Changes ◽  
Delta Receptor ◽  
Mu Opiate Receptor

Intraluminal administration of naloxone (10(-4) M), a mu-opiate receptor antagonist, or diprenorphine (10(-6) M), an opiate receptor antagonist with high affinity for both delta- and mu-receptors, decreased basal in vivo water and electrolyte absorption in the jejunum and ileum but not the colon of the rat. Diprenorphine (10(-5) M) decreased basal colonic water transport. These changes were not due to a reduction in mucosal Na-K-ATPase activity. Intravenous atropine prevented as well as abolished the changes in water transport due to naloxone. The diprenorphine-induced changes were not altered by atropine. Naloxone and diprenorphine acted by different receptors. Pretreatment with naloxone (10(-4) M) prevented the increase in water transport due to morphine, a mu-agonist, whereas a higher concentration of naloxone (10(-3) M) was required to inhibit the increase due to D-Ala-methionine-enkephalinamide, a delta-receptor agonist. In contrast, diprenorphine (10(-6) M) abolished the absorption caused by morphine and D-Ala-methionine-enkephalinamide. Diprenorphine (3 X 10(-7) M) partially prevented the morphine-induced increase in water absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Emerging era of microneedle array for pharmaceutical and biomedical applications: recent advances and toxicological perspectives

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shailesh Dugam ◽  
Rahul Tade ◽  
Rani Dhole ◽  
Sopan Nangare
Keyword(s):  
Biomedical Applications ◽  
Microneedle Array ◽  
Bioavailability Enhancement ◽  
Main Text ◽  
The Past ◽  
Recent Advancement ◽  
Insight Into

Abstract Background Microneedles (MNs) are the utmost unique, efficient, and minimally invasive inventions in the pharmaceutical field. Over the past decades, many scientists around the globe have reported MNs cautious because of their superb future in distinct areas. Concerning the wise use of MNs herein, we deal in depth with the present applications of MNs in drug delivery. Main text The present review comprises various fabrication materials and methods used for MN synthesis. The article also noted the distinctive advantages of these MNs, which holds huge potential for pharmaceutical and biomedical applications. The role of MNs in serving as a platform to treat various ailments has been explained accompanied by unusual approaches. The review also inculcates the pharmacokinetics of MNs, which includes permeation, absorption, and bioavailability enhancement. Besides this, the in vitro/in vivo toxicity, biosafety, and marketed product of MNs have been reviewed. We have also discussed the clinical trials and patents on the pharmaceutical applications of MNs in brief. Conclusion To sum up, this article gives insight into the MNs and provides a recent advancement in MNs, which pave the pathway for future pharmaceutical and biomedical applications. Graphical abstract Pharmaceutical and biomedical applications of MNs

scholarly journals Phosphorylation-induced changes in the PDZ domain of Dishevelled 3

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miroslav Jurásek ◽  
Jitender Kumar ◽  
Petra Paclíková ◽  
Alka Kumari ◽  
Konstantinos Tripsianes ◽  
...  
Keyword(s):  
Pdz Domain ◽  
Phosphorylation Sites ◽  
Pdz Domains ◽  
Recognition Motif ◽  
Regulation Mechanisms ◽  
Binding Groove ◽  
Dynamics Simulations ◽  
Induced Changes ◽  
Insight Into

AbstractThe PDZ domain of Dishevelled 3 protein belongs to a highly abundant protein recognition motif which typically binds short C-terminal peptides. The affinity of the PDZ towards the peptides could be fine-tuned by a variety of post-translation modifications including phosphorylation. However, how phosphorylations affect the PDZ structure and its interactions with ligands remains elusive. Combining molecular dynamics simulations, NMR titration, and biological experiments, we explored the role of previously reported phosphorylation sites and their mimetics in the Dishevelled PDZ domain. Our observations suggest three major roles for phosphorylations: (1) acting as an on/off PDZ binding switch, (2) allosterically affecting the binding groove, and (3) influencing the secondary binding site. Our simulations indicated that mimetics had similar but weaker effects, and the effects of distinct sites were non-additive. This study provides insight into the Dishevelled regulation by PDZ phosphorylation. Furthermore, the observed effects could be used to elucidate the regulation mechanisms in other PDZ domains.

scholarly journals THE ROLE OF HISTAMINE IN THE MECHANISM OF ANTIBIOTIC-INDUCED CHANGES IN COLONIC ION AND WATER TRANSPORT

2015 ◽  
Vol 62 (1) ◽  
pp. 95-101
Author(s):  
T.V. Dovbynchuk ◽  
◽  
T.M. Chervinska ◽  
L.V. Zakordonets ◽  
G.M. Тоlstanova G.M. Тоlstanova ◽  
...  
Keyword(s):  
Water Transport ◽  
Induced Changes

scholarly journals Stromal cues regulate the pancreatic cancer epigenome and metabolome

2017 ◽  
Vol 114 (5) ◽  
pp. 1129-1134 ◽  
Author(s):  
Mara H. Sherman ◽  
Ruth T. Yu ◽  
Tiffany W. Tseng ◽  
Cristovao M. Sousa ◽  
Sihao Liu ◽  
...  
Keyword(s):  
Ductal Adenocarcinoma ◽  
Oncogenic Signaling ◽  
Potential Therapeutic Target ◽  
Key Driver ◽  
Accelerated Growth ◽  
Induced Changes ◽  
Insight Into

A fibroinflammatory stromal reaction cooperates with oncogenic signaling to influence pancreatic ductal adenocarcinoma (PDAC) initiation, progression, and therapeutic outcome, yet the mechanistic underpinning of this crosstalk remains poorly understood. Here we show that stromal cues elicit an adaptive response in the cancer cell including the rapid mobilization of a transcriptional network implicated in accelerated growth, along with anabolic changes of an altered metabolome. The close overlap of stroma-induced changes in vitro with those previously shown to be regulated by oncogenic Kras in vivo suggests that oncogenic Kras signaling—a hallmark and key driver of PDAC—is contingent on stromal inputs. Mechanistically, stroma-activated cancer cells show widespread increases in histone acetylation at transcriptionally enhanced genes, implicating the PDAC epigenome as a presumptive point of convergence between these pathways and a potential therapeutic target. Notably, inhibition of the bromodomain and extraterminal (BET) family of epigenetic readers, and of Bromodomain-containing protein 2 (BRD2) in particular, blocks stroma-inducible transcriptional regulation in vitro and tumor progression in vivo. Our work suggests the existence of a molecular “AND-gate” such that tumor activation is the consequence of mutant Kras and stromal cues, providing insight into the role of the tumor microenvironment in the origin and treatment of Ras-driven tumors.

scholarly journals Role of Cells in Freezing-Induced Cell-Fluid-Matrix Interactions Within Engineered Tissues

2013 ◽  
Vol 135 (9) ◽  
Author(s):  
Angela Seawright ◽  
Altug Ozcelikkale ◽  
Craig Dutton ◽  
Bumsoo Han
Keyword(s):  
Water Transport ◽  
Extracellular Space ◽  
Intracellular Water ◽  
Cell Matrix ◽  
Engineered Tissues ◽  
Matrix Interactions ◽  
Cell Concentrations ◽  
Cellular Water ◽  
Cell Matrix Interactions ◽  
Cellular Water Transport

During cryopreservation, ice forms in the extracellular space resulting in freezing-induced deformation of the tissue, which can be detrimental to the extracellular matrix (ECM) microstructure. Meanwhile, cells dehydrate through an osmotically driven process as the intracellular water is transported to the extracellular space, increasing the volume of fluid for freezing. Therefore, this study examines the effects of cellular presence on tissue deformation and investigates the significance of intracellular water transport and cell-ECM interactions in freezing-induced cell-fluid-matrix interactions. Freezing-induced deformation characteristics were examined through cell image deformetry (CID) measurements of collagenous engineered tissues embedded with different concentrations of MCF7 breast cancer cells versus microspheres as their osmotically inactive counterparts. Additionally, the development of a biophysical model relates the freezing-induced expansion of the tissue due to the cellular water transport and the extracellular freezing thermodynamics for further verification. The magnitude of the freezing-induced dilatation was found to be not affected by the cellular water transport for the cell concentrations considered; however, the deformation patterns for different cell concentrations were different suggesting that cell-matrix interactions may have an effect. It was, therefore, determined that intracellular water transport during freezing was insignificant at the current experimental cell concentrations; however, it may be significant at concentrations similar to native tissue. Finally, the cell-matrix interactions provided mechanical support on the ECM to minimize the expansion regions in the tissues during freezing.

THE ROLE OF SPATIO-TEMPORAL IMAGING CORRELATION (STIC) IN THE PRENATAL DIAGNOSIS OF CONGENITAL HEART DEFECTS

2014 ◽  
Vol 25 (1) ◽  
pp. 59-72
Author(s):  
JIMMY ESPINOZA
Keyword(s):  
Fetal Heart ◽  
Heart Defects ◽  
Beating Heart ◽  
Image Correlation ◽  
Additional Insight ◽  
Spatio Temporal ◽  
And Function ◽  
Anatomical Information ◽  
Insight Into

Spatio-temporal image correlation (STIC) is a feature of four-dimensional ultrasonography (4D US) that allows the acquisition of volume datasets akin to blocks of pathological specimens, where all the anatomical information is contained in the block and the information displayed depends on the level at which the block is cut. STIC has the additional advantages that these planes can be assessed in a virtual beating heart, and that rendering techniques can be used to gain additional insight into the structure and function of the fetal heart.

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