scholarly journals The “Vesicular Intelligence” Strategy of Blood Cancers

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 416
Author(s):  
Dorian Forte ◽  
Martina Barone ◽  
Francesca Palandri ◽  
Lucia Catani
Keyword(s):  
Clonal Evolution ◽  
Biological Properties ◽  
Hemopoietic Stem Cell ◽  
Target Cells ◽  
Cancer Cell Growth ◽  
Cell Compartment ◽  
Blood Cancer ◽  
Non Invasive ◽  
Membrane Bound ◽  
Immune Potential

Blood cancers are a heterogeneous group of disorders including leukemia, multiple myeloma, and lymphoma. They may derive from the clonal evolution of the hemopoietic stem cell compartment or from the transformation of progenitors with immune potential. Extracellular vesicles (EVs) are membrane-bound nanovesicles which are released by cells into body fluids with a role in intercellular communication in physiology and pathology, including cancer. EV cargos are enriched in nucleic acids, proteins, and lipids, and these molecules can be delivered to target cells to influence their biological properties and modify surrounding or distant targets. In this review, we will describe the “smart strategy” on how blood cancer-derived EVs modulate tumor cell development and maintenance. Moreover, we will also depict the function of microenvironment-derived EVs in blood cancers and discuss how the interplay between tumor and microenvironment affects blood cancer cell growth and spreading, immune response, angiogenesis, thrombogenicity, and drug resistance. The potential of EVs as non-invasive biomarkers will be also discussed. Lastly, we discuss the clinical application viewpoint of EVs in blood cancers. Overall, blood cancers apply a ‘vesicular intelligence’ strategy to spread signals over their microenvironment, promoting the development and/or maintenance of the malignant clone.

scholarly journals An engineered membrane-bound guanylyl cyclase with light-switchable activity

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuehui Tian ◽  
Georg Nagel ◽  
Shiqiang Gao
Keyword(s):  
Guanylyl Cyclase ◽  
Green Light ◽  
Chemical Properties ◽  
Light Sensitivity ◽  
Cgmp Level ◽  
Volvox Carteri ◽  
Non Invasive ◽  
Cgmp Signaling ◽  
Membrane Bound ◽  
Light Flashes

Abstract Background Microbial rhodopsins vary in their chemical properties, from light sensitive ion transport to different enzymatic activities. Recently, a novel family of two-component Cyclase (rhod)opsins (2c-Cyclop) from the green algae Chlamydomonas reinhardtii and Volvox carteri was characterized, revealing a light-inhibited guanylyl cyclase (GC) activity. More genes similar to 2c-Cyclop exist in algal genomes, but their molecular and physiological functions remained uncharacterized. Results Chlamyopsin-5 (Cop5) from C. reinhardtii is related to Cr2c-Cyclop1 (Cop6) and can be expressed in Xenopus laevis oocytes, but shows no GC activity. Here, we exchanged parts of Cop5 with the corresponding ones of Cr2c-Cyclop1. When exchanging the opsin part of Cr2c-Cyclop1 with that of Cop5, we obtained a bi-stable guanylyl cyclase (switch-Cyclop1) whose activity can be switched by short light flashes. The GC activity of switch-Cyclop1 is increased for hours by a short 380 nm illumination and switched off (20-fold decreased) by blue or green light. switch-Cyclop1 is very light-sensitive and can half-maximally be activated by ~ 150 photons/nm2 of 380 nm (~ 73 J/m2) or inhibited by ~ 40 photons/nm2 of 473 nm (~ 18 J/m2). Conclusions This engineered guanylyl cyclase is the first light-switchable enzyme for cGMP level regulation. Light-regulated cGMP production with high light-sensitivity is a promising technique for the non-invasive investigation of the effects of cGMP signaling in many different tissues.

scholarly journals Isolation, Culture and Comprehensive Characterization of Biological Properties of Human Urine-Derived Stem cells

2021 ◽  
Vol 22 (22) ◽  
pp. 12503
Author(s):  
Martina Culenova ◽  
Andreas Nicodemou ◽  
Zuzana Varchulova Novakova ◽  
Michaela Debreova ◽  
Veronika Smolinská ◽  
...  
Keyword(s):  
Stem Cells ◽  
Low Cost ◽  
Biological Properties ◽  
Cytokine Profile ◽  
Rice Grain ◽  
Differentiation Potential ◽  
Secretory Rate ◽  
Gm Csf ◽  
Non Invasive ◽  
Cell Doubling Time

Mesenchymal stem cells (MSCs) represent an attractive source within the field of tissue engineering. However, their harvesting often requires invasive medical procedures. Urine-derived stem cells (UDSCs) display similar properties to MSCs, and their obtention and further processing is non-invasive for the donors as well as low cost. Here, we offer a comprehensive analysis of their biological properties. The goal of this study was to analyze their morphology, stemness, differentiation potential and cytokine profile. We have successfully isolated UDSCs from 25 urine samples. First colonies emerged up to 9 days after the initial seeding. Cell doubling time was 45 ± 0.24 SD, and when seeded at the density of 100 cells/cm2, they formed 42 ± 6.5 SD colonies within 10 days. Morphological analyzes revealed that two different types of the cell populations have been present. The first type had a rice-grain shape and the second one was characterized by a polyhedral shape. In several cell cultures, dome-shaped cells were observed as well. All examined UDSCs expressed typical MSC-like surface markers, CD73, CD90 and CD105. Moreover, conditioned media from UDSCs were harvested, and cytokine profile has been evaluated showing a significantly higher secretory rate of IL-8, IL-6 and chemokines MCP-1 and GM-CSF. We have also successfully induced human UDSCs into chondrogenic, osteogenic and myogenic cell lineages. Our findings indicate that UDSCs might have immense potential in the regeneration of the damaged tissues.

scholarly journals A 15 amino acid fragment of influenza nucleoprotein synthesized in the cytoplasm is presented to class I-restricted cytotoxic T lymphocytes.

1989 ◽  
Vol 170 (3) ◽  
pp. 1051-1056 ◽  
Author(s):  
K Gould ◽  
J Cossins ◽  
J Bastin ◽  
G G Brownlee ◽  
A Townsend
Keyword(s):  
Cell Clone ◽  
Recombinant Vaccinia Virus ◽  
Class I ◽  
Peptide Transport ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Recombinant Vaccinia ◽  
Acid Fragment ◽  
T Cell Clone ◽  
Membrane Bound

A recombinant vaccinia has been designed to express amino acids 366-379 of influenza nucleoprotein, previously shown to be the minimal epitope recognized by a class I-restricted cytotoxic T cell clone. Target cells infected with the recombinant vaccinia virus expressing this peptide are recognized by CTL as efficiently as target cells expressing the complete nucleoprotein. The results imply the existence of a peptide transport system that constitutively passes the products of degraded proteins from the cytoplasm into a membrane-bound compartment of the cell.

scholarly journals Position of O-Acetylation within the Capsular Repeat Unit Impacts the Biological Properties of Pneumococcal Serotypes 33A and 33F

2017 ◽  
Vol 85 (7) ◽  
Author(s):  
Brady L. Spencer ◽  
Jamil S. Saad ◽  
Anukul T. Shenoy ◽  
Carlos J. Orihuela ◽  
Moon H. Nahm
Keyword(s):  
Cell Wall ◽  
Repeat Unit ◽  
Biological Properties ◽  
Immune Recognition ◽  
Content Type ◽  
Pneumococcal Serotype ◽  
Membrane Bound ◽  
Biochemical Analyses ◽  
Opsonophagocytic Killing ◽  
Small Chemical

ABSTRACT Streptococcus pneumoniae (pneumococcus) produces many capsule types that differ in their abilities to evade host immune recognition. To explain these serotype-dependent protective capacities, many studies have investigated capsular thickness or the interaction of the capsule with complement proteins, but the effects of small chemical modifications of the capsule on its function have not been studied. One small chemical modification found frequently among pneumococcal capsules is O-acetylation. Pneumococcal serotype 33A has two membrane-bound O-acetyltransferase genes, wciG and wcjE. A 33A wcjE-deficient variant, 33F, occurs naturally and is increasing in prevalence in the wake of widespread conjugate vaccine use, but no wciG-deficient variants have been reported. To study the biological consequence of the loss of O-acetylation, we created wciG-deficient variants in both serotypes 33A and 33F, which we named 33X1 (ΔwciG) and 33X2 (ΔwciG ΔwcjE). Serotypes 33X1 and 33X2 express novel capsule types based on serological and biochemical analyses. We found that loss of WcjE-mediated O-acetylation appears not to affect cell wall shielding, since serotypes 33A and 33F exhibit comparable nonspecific opsonophagocytic killing, biofilm production, and adhesion to nasopharyngeal cells, though serotype 33F survived short-term drying better than serotype 33A. Loss of WciG-mediated O-acetylation in serotypes 33X1 and 33X2, however, resulted in a phenotype resembling that of nonencapsulated strains: increased cell wall accessibility, increased nonspecific opsonophagocytic killing, enhanced biofilm formation, and increased adhesion to nasopharyngeal cells. We conclude that WciG-mediated, but not WcjE-mediated, O-acetylation is important for producing protective capsules in 33A and that small chemical changes to the capsule can drastically affect its biological properties.

scholarly journals Targeted Molecular Imaging Using Aptamers in Cancer

2018 ◽  
Vol 11 (3) ◽  
pp. 71 ◽  
Author(s):  
Sorah Yoon ◽  
John Rossi
Keyword(s):  
Wide Spectrum ◽  
Rna Aptamers ◽  
Tissue Imaging ◽  
Live Cells ◽  
Target Cells ◽  
New Class ◽  
Non Invasive ◽  
Resolution Imaging ◽  
Tissue Specimens

Imaging is not only seeing, but also believing. For targeted imaging modalities, nucleic acid aptamers have features such as superior recognition of structural epitopes and quick uptake in target cells. This explains the emergence of an evolved new class of aptamers into a wide spectrum of imaging applications over the last decade. Genetically encoded biosensors tagged with fluorescent RNA aptamers have been developed as intracellular imaging tools to understand cellular signaling and physiology in live cells. Cancer-specific aptamers labeled with fluorescence have been used for assessment of clinical tissue specimens. Aptamers conjugated with gold nanoparticles have been employed to develop innovative mass spectrometry tissue imaging. Also, use of chemically conjugated cancer-specific aptamers as probes for non-invasive and high-resolution imaging has been transformative for in vivo imaging in multiple cancers.

scholarly journals Extracellular Vesicles as Biological Shuttles for Targeted Therapies

2019 ◽  
Vol 20 (8) ◽  
pp. 1848 ◽  
Author(s):  
Stefania Raimondo ◽  
Gianluca Giavaresi ◽  
Aurelio Lorico ◽  
Riccardo Alessandro
Keyword(s):  
Extracellular Vesicles ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Special Focus ◽  
Pathological Conditions ◽  
Critical Issues ◽  
Membrane Bound ◽  
And Function ◽  
Potential Use

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)—specialized membrane-bound nanocarriers for intercellular communication—suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, we will discuss the current developments in the field of animal and plant-derived EVs toward their potential use for delivery of therapeutic agents in different pathological conditions, with a special focus on cancer.

scholarly journals Differences in Shedding of the Interleukin-11 Receptor by the Proteases ADAM9, ADAM10, ADAM17, Meprin α, Meprin β and MT1-MMP

2019 ◽  
Vol 20 (15) ◽  
pp. 3677 ◽  
Author(s):  
Sammel ◽  
Peters ◽  
Lokau ◽  
Scharfenberg ◽  
Werny ◽  
...  
Keyword(s):  
Biologically Active ◽  
Target Cells ◽  
Matrix Metalloprotease ◽  
Bone Homeostasis ◽  
Inflammatory Conditions ◽  
Stat3 Phosphorylation ◽  
Membrane Bound ◽  
The Difference ◽  
Membrane Type ◽  
Interleukin 11

Interleukin-11 (IL-11) has been associated with inflammatory conditions, bone homeostasis, hematopoiesis, and fertility. So far, these functions have been linked to classical IL-11 signaling via the membrane bound receptor (IL-11R). However, a signaling cascade via the soluble IL-11R (sIL-11R), generated by proteolytic cleavage, can also be induced. This process is called IL-11 trans-signaling. A disintegrin and metalloprotease 10 (ADAM10) and neutrophil elastase were described as ectodomain sheddases of the IL-11R, thereby inducing trans-signaling. Furthermore, previous studies employing approaches for the stimulation and inhibition of endogenous ADAM-proteases indicated that ADAM10, but not ADAM17, can cleave the IL-11R. Herein, we show that several metalloproteases, namely ADAM9, ADAM10, ADAM17, meprin β, and membrane-type 1 matrix metalloprotease/matrix metalloprotease-14 (MT1-MMP/MMP-14) when overexpressed are able to shed the IL-11R. All sIL-11R ectodomains were biologically active and capable of inducing signal transducer and activator of transcription 3 (STAT3) phosphorylation in target cells. The difference observed for ADAM10/17 specificity compared to previous studies can be explained by the different approaches used, such as stimulation of protease activity or making use of cells with genetically deleted enzymes.

In Vitro Cytotoxicity Study of the Nano-Hydroxyapatite/Bacterial Cellulose Nanocomposites

2009 ◽  
Vol 610-613 ◽  
pp. 1011-1016 ◽  
Author(s):  
Yan Mei Chen ◽  
Ting Fei Xi ◽  
Yu Dong Zheng ◽  
Yi Zao Wan
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bacterial Cellulose ◽  
Bone Tissue ◽  
Biological Response ◽  
Biological Properties ◽  
In Vitro Cytotoxicity ◽  
National Standard ◽  
Target Cells

The nanocomposite of nano-hydroxyapatite/bacterial cellulose (nHA/BC) obtained by depositing in simulated body fluid (SBF), incorporating their excellent mechanical and biological properties, is expected to have potential applications in bone tissue engineering. However, the biological response evaluation of biomaterials is required to provide useful information to improve their design and application. In this article, the in vitro cytotoxicity of composites nHA/BC as well as its degradation residues was studied. Scanning electron microscopy (SEM) was used to observe the morphology of original materials and their degradation residues. The degree of degradation was evalued by measuring the concentration of reducing sugar (glucose) by ultraviolet spectrophotometer. Bone-forming osteoblasts (OB) and infinite culture cell line L929 fibroblasts were used to measure the cytotocixity of materials with MTT assay. Both kinds of cells in infusion proliferate greatly in a normal form and their relative growth rate (RGR) exceeds by 75%, which shows the cytotoxicity of materials is graded as 0~1, according to the national standard. Nevertheless, bone-forming OB cells, as a kind of target cells, are more susceptive on the cytotoxicity than infinite culture fibroblast cells L929. The results suggest the nanocomposite of nHA/BC without cytotoxicity is greatly promising as a kind of scaffold materials for bone tissue engineering and tissue functional cells are more suited to evaluate the cytotoxicity of biomedical materials.

scholarly journals Antimicrobial resistance, penicillin-binding protein sequences, and pilus islet carriage in relation to clonal evolution of Streptococcus pneumoniae serotype 19A in Russia, 2002–2013

2017 ◽  
Vol 145 (8) ◽  
pp. 1708-1719 ◽  
Author(s):  
N. MAYANSKIY ◽  
T. SAVINOVA ◽  
N. ALYABIEVA ◽  
O. PONOMARENKO ◽  
E. BRZHOZOVSKAYA ◽  
...  
Keyword(s):  
Molecular Detection ◽  
Susceptibility Testing ◽  
Clonal Complex ◽  
Binding Protein ◽  
Clonal Evolution ◽  
Clonal Structure ◽  
Penicillin Binding Protein ◽  
Non Invasive ◽  
Sequence Types

SUMMARYClonal changes of serotype 19A pneumococci have been appreciated in conjunction with growing prevalence of this serotype after implementation of the seven-valent pneumococcal conjugate vaccine (PCV7). In the present study, we characterized serotype 19A pneumococci collected in Russia within a decade preceding the implementation of PCV vaccination and described their clonal evolution. We retrospectively analyzed non-invasive serotype 19A isolates collected in 2002–2013. All isolates were subjected to multilocus sequence typing, antimicrobial susceptibility testing, determination of macrolide resistance genotype, molecular detection of pilus islet (PI) carriage, sequencing of penicillin-binding protein (PBP) genes. A total of 49 serotype 19A isolates represented 25 sequence types, of which 14 were newly described. The majority of isolates were distributed among clonal complex (CC) 663 (28%), CC230 (25%), CC156, and CC320 (14% each). CC663 and CC156 dominated in 2003, but were replaced by CC230 and CC320 later on; CC320 was only evident starting 2010. All isolates of CC663 and CC156 carried PI1; CC320 possessed both PI1 and PI2. The overall rate of altered amino acids in penicillin-nonsusceptible isolates was 13·9%, 7·2%, and 8·7% for PBP1a, PBP2b, and PBP2x, respectively. Our findings demonstrate that the clonal structure of serotype 19A pneumococci may evolve without PCV pressure.

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