Hyaluronic acid and Regenerative medicine: New insights into the stroke therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Maryam Shahi ◽  
Daruosh Mohammadnejad ◽  
Mohammad Karimipour ◽  
Seyed Hossein Rasta ◽  
Reza Rahbarghazi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Regenerative Medicine ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Stroke Therapy ◽  
Therapeutic Approaches ◽  
Normal Tissues ◽  
Inflammatory Processes

: Stroke is known as one of very important public health problems which are related to a societal burden and tremendous economic. It has been showed, there are few therapeutic approaches in the treatment of this disease. In this regard, present therapeutic platforms aim to obtain neuroprotection, reperfusion, and neurorecovery. Among these therapies, regenerative medicine-based therapies have been appeared as new ways in stroke therapy. Hyaluronic acid (HA) is a new candidate which could be applied as regerenative medicine-based therapy in the treatment of stroke. HA is a glycosaminoglycan which is formed of repeating disaccharide units (D-glucuronic acid and N-acetyl-D-glucosamine). Multiple lines evidence demonstrated that HA has critical roles in normal tissues. It can be key players in different physiological and pathophysiological conditions such as water homeostasis, multiple drug resistance, inflammatory processes, tumorigenesis, angiogenesis, and changed viscoelasticity of extracellular matrix. HA has very important physicochemical properties (i.e., availability of reactive functional groups and its solubility which makes it as a biocompatible material for applying in the regenerative medicine. Given that HA-based bioscaffolds and biomaterials do not induce inflammation or allergies and are hydrophilic which have introduced them as soft tissue fillers and injectable dermal. Several studies indicated that HA could be employed as new therapeutic candidate in the treatment of stroke. These studies documented that HA and HA-based therapies exert their pharmacology effects via affecting on stroke-related processes. Herein, we have summarized the role of extracellular matrix in stroke pathogenesis. Moreover, we highlighted the HA-based therapies in the treatment of stroke.

scholarly journals MicroRNA AND TUBERCULOSIS

2018 ◽  
Vol 8 (3) ◽  
pp. 309-315
Author(s):  
V. V. Eremeev ◽  
V. V. Evstifeev ◽  
G. S. Shepelkova ◽  
A. E. Ergeshova ◽  
M. A. Bagirov
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Fine Tuning ◽  
Tuberculosis Infection ◽  
Multiple Drug ◽  
Transcriptional Level ◽  
Genes Encoding ◽  
Mdr Tb ◽  
Inflammatory Processes

In 2015, more than 10% of tuberculosis (TB)-related deaths were attributable to M. tuberculosis with multiple drug-resistance (MDR-TB) and extensively drug-resistance (XDR-TB) (WHO 2016). In combination with insufficient commitment to the treatment regimen, the genetic heterogeneity and clonality of the patient's M. tuberculosis, as well as the poor permeability of the tuberculosis granuloma for the drug, can lead to monotherapy, despite the use of several drugs, which further promotes the spread of MDR and XDR-TB. Of particular concern is the rapid spread of resistance to newly introduced into clinical practice second-line drugs, intended for the treatment of MDR-TB — delamanid and bedaquiline. Thus, the spread of drug resistance to chemotherapy, along with the limited possibilities of chemotherapy in patients with MDR-TB and XDR-TB, dictate the need to supplement canonical chemotherapy with TB treatment methods directed at the host. MicroRNAs (miRs) are short sequences of single-stranded RNA that control up to 60% of genes encoding protein synthesis at a post-transcriptional level. Accumulating data points to the essential role of miRs in fine tuning the host response to infection, primarily by modulating the expression of proteins involved in the reactions of innate and adaptive immune responses. Despite the fact that the established functions of miRs activity are intracellular, a number of studies have discovered highly stable extracellular miRs circulating in blood. Currently, the possibility of using these molecules as biomarkers is being actively investigated. Chronic TB inflammation is characterized by parallel or step-bystep development of regulatory and pro-inflammatory processes that affect the severity and outcome of the disease. Both pro- and anti-inflammatory effects are elements of the bacterial strategy in the struggle for survival in the host organism. In this review we discuss the role of miRs as markers of tuberculosis infection, the nature and prognosis of the course of the disease, the involvement of miRs in the regulation of the innate and adaptive immunity in tuberculosis infection, and the perspectives for clinical usage of miRs as means for diagnosis and treatment of tuberculosis.

Role of integrons in the proliferation of multiple drug resistance in selected bacteria occurring in poultry production

2020 ◽  
Vol 61 (2) ◽  
pp. 122-131
Author(s):  
P. Racewicz ◽  
M. Majewski ◽  
Z. E. Madeja ◽  
A. Łukomska ◽  
M. Kubiak
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Poultry Production

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

2012 ◽  
Author(s):  
Angela Seawright ◽  
Altug Ozcelikkale ◽  
J. Craig Dutton ◽  
Bumsoo Han
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Regenerative Medicine ◽  
Biological Tissues ◽  
Cellular Viability ◽  
Long Term Storage ◽  
Matrix Interactions ◽  
Term Storage

Cryopreservation can provide long-term storage of various biological tissues, which has significant impact on tissue engineering and regenerative medicine. For successful cryopreservation of tissues, tissue functionality must be maintained including physical properties such as mechanical, optical, and transport properties, as well as cellular viability. Such properties are associated with the extracellular matrix (ECM) microstructure. Thus, the preservation of the ECM microstructure may lead to successful cryopreservation [1,2]. Yet, there is still very little known about changes in the ECM microstructure during freezing/thawing.

scholarly journals Overexpression of the insulin-like growth factor I receptor in human pheochromocytomas

2006 ◽  
Vol 36 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Christian Fottner ◽  
Timo Minnemann ◽  
Sarah Kalmbach ◽  
Matthias M Weber
Keyword(s):  
Scatchard Analysis ◽  
Mrna Levels ◽  
Therapeutic Approaches ◽  
Binding Studies ◽  
Single Class ◽  
Normal Tissues ◽  
Igf System ◽  
Igf I ◽  
Polymerase Chain

In order to determine the role of the IGF-I receptor (IGF-IR) in human pheochromocytomas we have compared the expression of the IGF-IR in normal tissues and in pheochromocytomas with regard to the IGF-IR mRNA levels and ligand binding. By semiquantitative reverse transcription polymerase chain reaction (RT-PCR), the mRNA of the IGF-IR could be detected in all samples of normal adrenomedullary cells (n=13) and pheochromocytomas (n=16). However, pheochromocytomas exhibited 2.8-fold higher mean IGF-IR mRNA levels than normal adrenomedullary cells (2.8±0.5×105 molecules/μg RNA vs 7.8±1.2×105 molecules/μg RNA; P < 0.001). This overexpression of the IGF-IR in pheochromocytomas could be confirmed at the protein level by binding studies. Radioligand assays and Scatchard analysis revealed a single class of high affinity IGF-IR binding sites with a similar dissociation constant (Kd: 0.32±0.1 nmol/l vs 0.22±0.08 nmol/l) for both normal adrenomedullary cells and pheochromocytomas. However, specific 125I-labeled IGF-I binding and the calculated receptor concentration were significantly elevated in pheochromocytomas as compared with normal adrenomedullary cells (58.3±5 vs 24.3±12 nmol/kg protein; P < 0.05). In summary, our results demonstrate significant overexpression of the IGF-IR in human pheochromocytomas. This suggests a possible role of the IGF system in the pathogenesis of adrenal neoplasia and thus IGF-IR may be a target for future therapeutic approaches.

scholarly journals Role of NADPH Phagocyte Oxidase in Host Defense against Acute Respiratory Acinetobacter baumannii Infection in Mice

2008 ◽  
Vol 77 (3) ◽  
pp. 1015-1021 ◽  
Author(s):  
Hongyu Qiu ◽  
Rhonda KuoLee ◽  
Greg Harris ◽  
Wangxue Chen
Keyword(s):  
Acinetobacter Baumannii ◽  
Host Defense ◽  
Multiple Drug Resistance ◽  
Bacterial Pathogen ◽  
Inflammatory Cells ◽  
Multiple Drug ◽  
Moderate Increase ◽  
Phagocyte Oxidase ◽  
Bacterial Replication

ABSTRACT Acinetobacter baumannii is an emerging bacterial pathogen that rapidly develops multiple-drug resistance and is responsible for many nosocomial pulmonary infections. This study investigated the role of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (NOS2) in the host defense against respiratory infection with A. baumannii in mouse models of intranasal A. baumannii infection. gp91phox−/− mice showed higher susceptibility to A. baumannii infection than wild-type (WT) C57BL/6 mice, with significantly greater bacterial counts in their lungs (1,000-fold) (P < 0.005) and spleens (10-fold) (P < 0.05). Moreover, all of the gp91phox−/− mice succumbed to infection within 48 h. In contrast, only a moderate increase in bacterial burdens was detected in the lungs of NOS2−/− mice, and all NOS2−/− mice survived infection. Compared to WT mice, the pulmonary influx of inflammatory cells and serum and local inflammatory cytokine/chemokine responses were not obviously impaired at 4 h and were significantly higher at 24 h (P < 0.05) in gp91phox−/− mice, but NADPH-deficient neutrophils were unable to control bacterial replication and extrapulmonary dissemination. Thus, NADPH phagocyte oxidase appears to play a crucial role in the neutrophil-mediated host defense against A. baumannii.

scholarly journals Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens

2019 ◽  
Author(s):  
Sara Pedron ◽  
Gabrielle L. Wolter ◽  
Jee-Wei E. Chen ◽  
Sarah E. Laken ◽  
Jann N. Sarkaria ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Tumor Microenvironment ◽  
Kinase Inhibitor ◽  
Egfr Mutations ◽  
Primary Glioblastoma ◽  
Stat3 Phosphorylation

AbstractTherapeutic options to treat primary glioblastoma (GBM) tumors are scarce. GBM tumors with epidermal growth factor receptor (EGFR) mutations, in particular a constitutively active EGFRvIII mutant, have extremely poor clinical outcomes. GBM tumors with concurrent EGFR amplification and active phosphatase and tensin homolog (PTEN) are sensitive to the tyrosine kinase inhibitor erlotinib, but the effect is not durable. A persistent challenge to improved treatment is the poorly understood role of cellular, metabolic, and biophysical signals from the GBM tumor microenvironment on therapeutic efficacy and acquired resistance. The intractable nature of studying GBM cell in vivo motivates tissue engineering approaches to replicate aspects of the complex GBM tumor microenvironment. Here, we profile the effect of erlotinib on two patient-derived GBM specimens: EGFR+ GBM12 and EGFRvIII GBM6. We use a three-dimensional gelatin hydrogel to present brain-mimetic hyaluronic acid (HA) and evaluate the coordinated influence of extracellular matrix signals and EGFR mutation status on GBM cell migration, survival and proliferation, as well as signaling pathway activation in response to cyclic erlotinib exposure. Comparable to results observed in vivo for xenograft tumors, erlotinib exposure is not cytotoxic for GBM6 EGFRvIII specimens. We also identify a role of extracellular HA (via CD44) in altering the effect of erlotinib in GBM EGFR+ cells by modifying STAT3 phosphorylation status. Taken together, we report an in vitro tissue engineered platform to monitor signaling associated with poor response to targeted inhibitors in GBM.

scholarly journals TISSUE ENGINEERING: FROM RESEARCH TO CLINICAL APPLICATION IN REGENERATIVE MEDICINE

1970 ◽  
pp. 159-192
Author(s):  
Enrico Tognana ◽  
Lanfranco Callegaro
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Regenerative Medicine ◽  
Therapeutic Option ◽  
Cartilage Tissue ◽  
Sequence Of Events ◽  
Benzyl Esters ◽  
Tissue Restoration

Tissue engineering strategies have recently emerged as the most advanced therapeutic option presently available in regenerative medicine. Tissue engineering encompasses the use of cells and their molecules in artificial constructs that compensate for lost or impaired body functions. It is based upon scaffoldguided tissue regeneration and involves the seeding of porous, biodegradable scaffolds with donor cells, which become differentiated and mimic naturally occurring tissues. These tissue-engineered constructs are then implanted into the patient to replace diseased or damaged tissues. Our approach to regenerative medicine is based on hyaluronan derivative polymers. HYAFF® is a class of hyaluronan derivative polymers obtained by coupling reaction. The strategy behind the creation of these polymers was to improve the stability of the polymer by esterifying the free carboxyl group of glucuronic acid, frequently repeated along the hyaluronic acid chain, with different types of alcohols. Once esterification of the polymer has been obtained, the material can easily be processed to produce membranes, fibres, sponges, microspheres and other devices, by extrusion, lyophilization or spray drying. A broad variety of polymers can be subsequently generated either by changing the type of ester group introduced or the extent of the esterification. The benzyl esters of hyaluronan, termed HYAFF®-11, are one of the most characterized HYAFF® polymers, from both the physicochemical and biological viewpoints, produced starting from hyaluronan of about 200 KDa. The ideal scaffold for tissue engineering should provide an immediate support to cells and have mechanical properties matching those of the tissue being repaired. Gradually then the material should be resorbed, as the cells begin secreting their own extracellular matrix, thus allowing for an optimal integration between newformed and existing tissue. Extensive biocompatibility studies have demonstrated the safety of HYAFF® scaffolds and their ability to be resorbed in the absence of an inflammatory response. Moreover, when implanted tend to promote the recapitulation of the events that facilitate tissue repair. HYAFF®-11 three-dimensional matrices support the in vitro growth of highly viable chondrocytes and fibroblasts. Similarly, micro-perforated membrane supports the growth and differentiation of keratinocytes. These cells, previously expanded on plastic and hence seeded into the HYAFF® scaffold, produce a characteristic extracellular matrix rich in proteoglycans expressing the typical markers of the tissues of their origin. Hyaluronan presents a variety of multi-functional activity being both a structural and informational molecule. Investigation of hyaluronan synthesis and degradation, the identification of new receptors and binding proteins and the elucidation of hyaluronan-dependent signaling pathways keep providing novel insights into the true biological functions of this intriguing polymer. The possibility to elaborate this natural polymer in different physical forms, as HYAFF® biopolymers family is allowing to do, has given the opportunity to translate tissue engineering strategies in clinical practice providing a biomaterial that induces and modulates the sequence of events that lead to damage tissue restoration. The following chapter will report how tissue engineering approach and hyaluronic acid technology could improve the biological function of cell transplantation in the treatment of tissue defects, in particular for skin and cartilage tissue restoration.

Role of the MDR-1-Encoded Multiple Drug Resistance Phenotype in Prostate Cancer Cell Lines

1993 ◽  
Vol 150 (5 Part 1) ◽  
pp. 1544-1547 ◽  
Author(s):  
Gerhard Theyer ◽  
Marion Schirmböck ◽  
Therese Thalhammer ◽  
Edward R. Sherwood ◽  
Gerhard Baumgartner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Prostate Cancer Cell Lines ◽  
Mdr 1

The crosstalk of hyaluronan-based extracellular matrix and synapses

2008 ◽  
Vol 4 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Renato Frischknecht ◽  
Constanze I. Seidenbecher
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Hyaluronic Acid ◽  
Chondroitin Sulphate ◽  
Specific Form ◽  
Perineuronal Net ◽  
Chondroitin Sulphate Proteoglycans ◽  
And Function ◽  
Brain Extracellular Space

Many neurons and their synapses are enwrapped in a brain-specific form of the extracellular matrix (ECM), the so-called perineuronal net (PNN). It forms late in the postnatal development around the time when synaptic contacts are stabilized. It is made of glycoproteins and proteoglycans of glial as well as neuronal origin. The major organizing polysaccharide of brain extracellular space is the polymeric carbohydrate hyaluronic acid (HA). It forms the backbone of a meshwork consisting of CNS proteoglycans such as the lectican family of chondroitin sulphate proteoglycans (CSPG). This family comprises four abundant components of brain ECM: aggrecan and versican as broadly expressed CSPGs and neurocan and brevican as nervous-system-specific family members. In this review, we intend to focus on the specific role of the HA-based ECM in synapse development and function.

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