scholarly journals Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels

2019 ◽  
Vol 5 (3) ◽  
pp. eaav1281 ◽  
Author(s):  
Ehsan Shirzaei Sani ◽  
Ahmad Kheirkhah ◽  
Devyesh Rana ◽  
Zhongmou Sun ◽  
William Foulsham ◽  
...  
Keyword(s):  
Low Cost ◽  
Unmet Need ◽  
Defect Model ◽  
Sutureless Repair ◽  
In Vivo Experiments ◽  
High Adhesion ◽  
Common Causes ◽  
Corneal Regeneration

Corneal injuries are common causes of visual impairment worldwide. Accordingly, there is an unmet need for transparent biomaterials that have high adhesion, cohesion, and regenerative properties. Herein, we engineer a highly biocompatible and transparent bioadhesive for corneal reconstruction using a visible light cross-linkable, naturally derived polymer, GelCORE (gel for corneal regeneration). The physical properties of GelCORE could be finely tuned by changing prepolymer concentration and photocrosslinking time. GelCORE revealed higher tissue adhesion compared to commercial adhesives. Furthermore, in situ photopolymerization of GelCORE facilitated easy delivery to the cornea, allowing for bioadhesive curing precisely according to the required geometry of the defect. In vivo experiments, using a rabbit stromal defect model, showed that bioadhesive could effectively seal corneal defects and induce stromal regeneration and re-epithelialization. Overall, GelCORE has many advantages including low cost and ease of production and use. This makes GelCORE a promising bioadhesive for corneal repair.

scholarly journals Enlisting the Ixodes scapularis Embryonic ISE6 Cell Line to Investigate the Neuronal Basis of Tick—Pathogen Interactions

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 70
Author(s):  
Lourdes Mateos-Hernández ◽  
Natália Pipová ◽  
Eléonore Allain ◽  
Céline Henry ◽  
Clotilde Rouxel ◽  
...  
Keyword(s):  
Cell Line ◽  
Peripheral Nerves ◽  
Ixodes Scapularis ◽  
Embryonic Cell ◽  
Cell Subpopulation ◽  
In Vivo Experiments

Neuropeptides are small signaling molecules expressed in the tick central nervous system, i.e., the synganglion. The neuronal-like Ixodes scapularis embryonic cell line, ISE6, is an effective tool frequently used for examining tick–pathogen interactions. We detected 37 neuropeptide transcripts in the I. scapularis ISE6 cell line using in silico methods, and six of these neuropeptide genes were used for experimental validation. Among these six neuropeptide genes, the tachykinin-related peptide (TRP) of ISE6 cells varied in transcript expression depending on the infection strain of the tick-borne pathogen, Anaplasma phagocytophilum. The immunocytochemistry of TRP revealed cytoplasmic expression in a prominent ISE6 cell subpopulation. The presence of TRP was also confirmed in A. phagocytophilum-infected ISE6 cells. The in situ hybridization and immunohistochemistry of TRP of I. scapularis synganglion revealed expression in distinct neuronal cells. In addition, TRP immunoreaction was detected in axons exiting the synganglion via peripheral nerves as well as in hemal nerve-associated lateral segmental organs. The characterization of a complete Ixodes neuropeptidome in ISE6 cells may serve as an effective in vitro tool to study how tick-borne pathogens interact with synganglion components that are vital to tick physiology. Therefore, our current study is a potential stepping stone for in vivo experiments to further examine the neuronal basis of tick–pathogen interactions.

Phosphofructokinase activity and acidosis during short-term tetanic contractions

1991 ◽  
Vol 69 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Lawrence L. Spriet
Keyword(s):  
Glycolytic Enzyme ◽  
Test Tube ◽  
Mammalian Skeletal Muscle ◽  
Short Term ◽  
Short Supply ◽  
In Vivo Experiments ◽  
Anaerobic Energy

Anaerobic energy production is essential for the production of muscular tension when the demand for energy is greater than can be provided aerobically and when oxygen is in short supply. The largest source of anaerobic energy is from the glycolytic pathway. With sustained tetanic contractions, muscle glycolytic activity is high and hydrogen ions (H+) accumulate while tension production decreases. The increasing [H+] and decreasing tension led to the suggestion that H+ inhibits the activity of the regulatory glycolytic enzyme phosphofructokinase (PFK). Early in vitro work confirmed the H+ sensitivity of PFK in the test tube, indicating that little PFK activity should persist at a pH of 6.9–7.0. However, in situ and in vivo experiments suggested that significant PFK activity was maintained during intense contractions when muscle pH decreased to 6.4–6.6. There are several concerns associated with the application of in vitro findings to in vivo exercise situations: (i) there is little in vitro work in mammalian skeletal muscle with substrate and modulator concentrations representative of exercise, (ii) most in vitro analyses of PFK activity are performed following the dilution of the enzyme in mediums with low protein concentration, and (iii) do the modulators identified in vitro exist in high enough in vivo concentrations at rest and during exercise to contribute to the regulation of PFK? More recent in vitro and in situ PFK experiments have overcome some of these concerns. They confirm that during intense, short-term tetanic contractions, PFK activity is well matched to the ATP demand despite decreases in pH to ~6.4–6.5. A combination of decreased inhibitor (ATP) and increased substrate (fructose 6-phosphate) contents coupled with increases in the contents of several positive modulators may be responsible for the maintained PFK activity. This combination reduces the pH-dependent ATP inhibition of PFK and extends the physiological pH range of the enzyme to the range normally measured during this type of muscular activity.Key words: glycolysis, phosphofructokinase, anaerobic metabolism, acidosis.

Antegrade in situ fenestration of aortic stent graft: in-vivo experiments using a pig model

2012 ◽  
Vol 53 (7) ◽  
pp. 754-758 ◽  
Author(s):  
Petri Saari ◽  
Markku Lähteenvuo ◽  
Krista Honkonen ◽  
Hannu Manninen
Keyword(s):  
Stent Graft ◽  
Pig Model ◽  
In Vivo Experiments ◽  
Aortic Stent Graft

scholarly journals Multiphasic construct studied in an ectopic osteochondral defect model

2014 ◽  
Vol 11 (95) ◽  
pp. 20140184 ◽  
Author(s):  
June E. Jeon ◽  
Cédryck Vaquette ◽  
Christina Theodoropoulos ◽  
Travis J. Klein ◽  
Dietmar W. Hutmacher
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Osteochondral Defect ◽  
Low Cost ◽  
Current Model ◽  
Large Animal ◽  
Micro Computed Tomography ◽  
Defect Model ◽  
Osteochondral Repair

In vivo osteochondral defect models predominantly consist of small animals, such as rabbits. Although they have an advantage of low cost and manageability, their joints are smaller and more easily healed compared with larger animals or humans. We hypothesized that osteochondral cores from large animals can be implanted subcutaneously in rats to create an ectopic osteochondral defect model for routine and high-throughput screening of multiphasic scaffold designs and/or tissue-engineered constructs (TECs). Bovine osteochondral plugs with 4 mm diameter osteochondral defect were fitted with novel multiphasic osteochondral grafts composed of chondrocyte-seeded alginate gels and osteoblast-seeded polycaprolactone scaffolds, prior to being implanted in rats subcutaneously with bone morphogenic protein-7. After 12 weeks of in vivo implantation, histological and micro-computed tomography analyses demonstrated that TECs are susceptible to mineralization. Additionally, there was limited bone formation in the scaffold. These results suggest that the current model requires optimization to facilitate robust bone regeneration and vascular infiltration into the defect site. Taken together, this study provides a proof-of-concept for a high-throughput osteochondral defect model. With further optimization, the presented hybrid in vivo model may address the growing need for a cost-effective way to screen osteochondral repair strategies before moving to large animal preclinical trials.

scholarly journals Application of a simple device for "attracting" and "trapping" glioma cells in situ

2021 ◽  
Author(s):  
Haimin Song ◽  
Runwei Yang ◽  
Runbin Lai ◽  
Kaishu Li ◽  
Bowen Ni ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Adult Brain ◽  
Tumor Bed ◽  
In Vivo Experiments ◽  
New Strategy ◽  
New Treatment

Glioblastoma multiforme (GBM) is the most malignant adult brain tumor. The current adjuvant therapies for GBM are disappointing, which are based on cytotoxicity strategy. Thus, other ways should be explored to improve the curative effect. According to the strong invasive ability of GBM cells, we assume a new treatment strategy for GBM by developing a new cell trap device (CTD) with some kind of "attractive" medium loaded in it to attract and capture the tumor cells. The in vitro experiment showed that Hepatocyte Growth Factor（HGF）presented stronger chemotaxis on C6 and U87 cell line than the Epidermal Growth Factor (EGF) and Fibroblast Growth Factor (FGF). A simple in vitro CTD loaded with HGF was made and in vivo experiments results showed that HGF successfully attracted tumor cells from tumor bed in situ into the CTD. This study proposes the new strategy for GBM treatment of "attract and trap" tumor cells is proved to be feasible.

Antitumor activity of osimertinib in NSCLC harboring EGFR exon 20 insertions.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9030-9030 ◽  
Author(s):  
Jonathan Riess ◽  
Nicolas Floch ◽  
Matthew Martin ◽  
Jonathon Orme ◽  
Anna Staniszewska ◽  
...  
Keyword(s):  
Unmet Need ◽  
Tumor Growth Inhibition ◽  
Drug Discontinuation ◽  
Tumor Shrinkage ◽  
In Vivo Experiments ◽  
Activating Mutation ◽  
Exon 20 ◽  
Egfr Tki ◽  
Egfr Tkis

9030 Background: EGFR exon 20 insertions (Ex20Ins), the 3rd most common EGFR activating mutation, are generally unresponsive to 1st and 2nd generation EGFR-TKIs. Development of EGFR-TKIs that effectively target NSCLC with Ex20Ins mutations represents a major unmet need. Osimertinib is an EGFR TKI approved for the treatment of advanced NSCLC harboring EGFR T790M, but the potential of osimertinib remains to be fully assessed in patients (pts) with Ex20Ins NSCLC. Methods: CRISPR engineered Ex20Ins cell line xenografts representing the two most common Ex20Ins (D770_N771InsSVD and V769_D770InsASV) and pt derived xenograft (PDX) of 3 EGFR Ex20Ins (V769_D770InsASV, M766_A767insASV, H773_V774insNPH) were used for in vivo experiments. Xenografts were treated by oral gavage with vehicle, erlotinib (50 mg/kg/day) or afatinib (20 mg/kg/day), osimertinib metabolite AZ5104 (50 mg/kg/day) and osimertinib (25 mg/kg/day) and assessed for tumor growth inhibition (TGI). Immunoblotting was performed for EGFR and relevant signaling pathways. A pt from whom the V769_D770InsASV Ex20ins PDX was derived was treated on a UC Davis IRB approved protocol with osimertinib at 160 mg PO once-daily (QD). Results: At completion of treatment, QD administration of osimertinib or AZ5104 induced significant TGI in xenografts across the 4 EGFR Ex20ins tested (range 60-95% TGI, p < 0.001 compared to control for all models) that was superior to either afatinib or erlotinib. Robust decrease in p-EGFR, p-ERK, p-Akt, p-Stat3 was observed with osimertinib treatment. The patient corresponding to the V769_D770InsASV Ex20ins PDX treated with osimertinib exhibited clinical improvement and tumor shrinkage; unfortunately he was found to have interstitial pneumonitis that necessitated drug discontinuation. Conclusions: Osimertinib at clinically representative doses has in vivo activity across multiple EGFR Ex20ins that comprising the most common Ex20ins detected in patients (~50% prevalence); metabolite AZ5104 may contribute to efficacy. Tumor shrinkage was observed in a patient with lung cancer harboring an Ex20ins treated for a limited time with osimertinib. Based on this in vivo xenograft and pt data, osimertinib warrants further study in pts with EGFR Ex20ins NSCLC.

Ion-pair strategy for enabling amifostine oral absorption: Rat in situ and in vivo experiments

2013 ◽  
Vol 49 (4) ◽  
pp. 499-504 ◽  
Author(s):  
N. Samiei ◽  
V. Mangas-Sanjuan ◽  
I. González-Álvarez ◽  
M. Foroutan ◽  
A. Shafaati ◽  
...  
Keyword(s):  
Oral Absorption ◽  
Ion Pair ◽  
In Vivo Experiments

scholarly journals Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological and pathological disease in a Syrian hamster model of COVID-19

2021 ◽  
Author(s):  
Thomas J Esparza ◽  
Yaozong Chen ◽  
Negin P Martin ◽  
Helle Bielefeldt-Ohmann ◽  
Richard A Bowen ◽  
...  
Keyword(s):  
Syrian Hamster ◽  
Low Cost ◽  
Unmet Need ◽  
Lung Pathology ◽  
Hamster Model ◽  
Angiotensin Converting Enzyme 2 ◽  
In Vitro Characterization ◽  
Pathological Disease

There remains an unmet need for globally deployable, low-cost therapeutics for the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Previously, we reported on the isolation and in vitro characterization of a potent single-domain nanobody, NIH-CoVnb-112, specific for the receptor binding domain (RBD) of SARS-CoV-2. Here, we report on the molecular basis for the observed broad in vitro neutralization capability of NIH-CoVnb-112 against variant SARS-CoV-2 pseudoviruses, including the currently dominant Delta variant. The structure of NIH-CoVnb-112 bound to SARS-CoV-2 RBD reveals a large contact surface area overlapping the angiotensin converting enzyme 2 (ACE2) binding site, which is largely unencumbered by the common RBD mutations. In an in vivo pilot study, we demonstrate effective reductions in weight loss, viral burden, and lung pathology in a Syrian hamster model of COVID-19 following nebulized delivery of NIH-CoVnb-112. These findings support the further development of NIH-CoVnb-112 as a potential adjunct preventative therapeutic for the treatment of SARS-CoV-2 infection.

Computational modelling of maternal interactions with spermatozoa: potentials and prospects

2011 ◽  
Vol 23 (8) ◽  
pp. 976 ◽  
Author(s):  
Mark Burkitt ◽  
Dawn Walker ◽  
Daniela M. Romano ◽  
Alireza Fazeli
Keyword(s):  
Reproductive Tract ◽  
Computational Modelling ◽  
Female Reproductive Tract ◽  
In Vivo Experiments ◽  
Complex Interactions ◽  
Maternal Communication ◽  
In Silico Models

Understanding the complex interactions between gametes, embryos and the maternal tract is required knowledge for combating infertility and developing new methods of contraception. Here we present some main aspects of spermatozoa interactions with the mammalian oviduct before fertilisation and discuss how computational modelling can be used as an invaluable aid to experimental investigation in this field. A complete predictive computational model of gamete and embryo interactions with the female reproductive tract is a long way off. However, the enormity of this task should not discourage us from working towards it. Computational modelling allows us to investigate aspects of maternal communication with gametes and embryos, which are financially, ethically or practically difficult to look at experimentally. In silico models of maternal communication with gametes and embryos can be used as tools to complement in vivo experiments, in the same way as in vitro and in situ models.

scholarly journals A Sparsity-Constrained Preconditioned Kaczmarz Reconstruction Method for Fluorescence Molecular Tomography

2016 ◽  
Vol 2016 ◽  
pp. 1-15
Author(s):  
Duofan Chen ◽  
Jimin Liang ◽  
Yao Li ◽  
Guanghui Qiu
Keyword(s):  
Low Cost ◽  
Biological Tissues ◽  
Reconstruction Method ◽  
Fluorescence Molecular Tomography ◽  
In Vivo Experiments ◽  
Fluorescent Markers ◽  
Ill Posed ◽  
Kaczmarz Method ◽  
Memory Efficient

Fluorescence molecular tomography (FMT) is an imaging technique that can localize and quantify fluorescent markers to resolve biological processes at molecular and cellular levels. Owing to a limited number of measurements and a large number of unknowns as well as the diffusive transport of photons in biological tissues, the inverse problem in FMT is usually highly ill-posed. In this work, a sparsity-constrained preconditioned Kaczmarz (SCP-Kaczmarz) method is proposed to reconstruct the fluorescent target for FMT. The SCP-Kaczmarz method uses the preconditioning strategy to minimize the correlation between the rows of the forward matrix and constrains the Kaczmarz iteration results to be sparse. Numerical simulation and phantom and in vivo experiments were performed to test the efficiency of the proposed method. The results demonstrate that both the convergence and accuracy of the proposed method are improved compared with the classical memory-efficient low-cost Kaczmarz method.

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