scholarly journals A Sequential Therapeutic Hydrogel With Injectability and Antibacterial Activity for Deep Burn Wounds’ Cleaning and Healing

2021 ◽  
Vol 9 ◽  
Author(s):  
Sizhen Wang ◽  
Jie Li ◽  
Zhiqiang Ma ◽  
Linhong Sun ◽  
Lei Hou ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Wound Dressing ◽  
Sequential Therapy ◽  
Burn Injuries ◽  
Burn Wounds ◽  
The Core ◽  
Clinical Challenge ◽  
First Time

As a severe clinical challenge, escharotomy and infection are always the core concerns of deep burn injuries. However, a usual dressing without multifunctionality leads to intractable treatment on deep burn wounds. Herein, we fabricated a sequential therapeutic hydrogel to solve this problem. Cross-linked by modified polyvinyl alcohol (PVA-SH/ε-PL) and benzaldehyde-terminated F127 triblock copolymers (PF127-CHO), the hydrogel demonstrated excellent mechanical properties, injectability, tissue adhesiveness, antibacterial activity, biocompatibility, and satisfactory wound cleaning through both in vitro and in vivo assays. Additionally, based on the conception of “sequential therapy,” we proposed for the first time to load bromelain and EGF into the same hydrogel in stages for wound cleaning and healing. This work provides a strategy to fabricate a promising wound dressing for the treatment of deep burn wounds with injectability and improved patients’ compliance as it simplified the process of treatment due to its “three in one” characteristic (antibacterial activity, wound cleaning, and healing effects); therefore, it has great potential in wound dressing development and clinical application.

scholarly journals Fabrication and characterization of an antibacterial chitosan/silk fibroin electrospun nanofiber loaded with a cationic peptide for wound-dressing application

2021 ◽  
Vol 32 (9) ◽  
Author(s):  
Sadjad Khosravimelal ◽  
Milad Chizari ◽  
Behrouz Farhadihosseinabadi ◽  
Mehrdad Moosazadeh Moghaddam ◽  
Mazaher Gholipourmalekabadi
Keyword(s):  
Antibacterial Activity ◽  
Silk Fibroin ◽  
Wound Dressing ◽  
Treatment Strategies ◽  
High Water ◽  
Wound Dressings ◽  
Electrospun Nanofiber ◽  
Cationic Antimicrobial Peptide

AbstractWound infections are still problematic in many cases and demand new alternatives for current treatment strategies. In recent years, biomaterials-based wound dressings have received much attention due to their potentials and many studies have been performed based on them. Accordingly, in this study, we fabricated and optimized an antibacterial chitosan/silk fibroin (CS/SF) electrospun nanofiber bilayer containing different concentrations of a cationic antimicrobial peptide (AMP) for wound dressing applications. The fabricated CS/SF nanofiber was fully characterized and compared to the electrospun silk fibroin and electrospun chitosan alone in vitro. Then, the release rate of different concentrations of peptide (16, 32, and 64 µg/ml) from peptide-loaded CS/SF nanofiber was investigated. Finally, based on cytotoxic activity, the antibacterial activity of scaffolds containing 16 and 32 µg/ml of the peptide was evaluated against standard and multi-drug resistant strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa isolated from burn patients. The peptide-loaded CS/SF nanofiber displayed appropriate mechanical properties, high water uptake, suitable biodegradation rate, a controlled release without cytotoxicity on Hu02 human foreskin fibroblast cells at the 16 and 32 µg/ml concentrations of peptide. The optimized CS/SF containing 32 μg/ml peptide showed strong antibacterial activity against all experimental strains from standard to resistance. The results showed that the fabricated antimicrobial nanofiber has the potential to be applied as a wound dressing for infected wound healing, although further studies are needed in vivo.

119 A Nitric Oxide Releasing Bio-active Wound Dressing for Burn Wound Infection Treatment

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S79-S80
Author(s):  
Jahnabi Roy ◽  
Lori Estes ◽  
Robert J Christy ◽  
Hitesh Handa ◽  
Shanmugasundaram Natesan
Keyword(s):  
Wound Healing ◽  
Wound Infection ◽  
Wound Dressing ◽  
Healing Process ◽  
Fibroblast Proliferation ◽  
Burn Wound ◽  
Burn Wounds ◽  
Log Reduction

Abstract Introduction The future of multi-domain battlefield operation requires wound dressings to prevent infection at the point of injury. Majority of antimicrobial agents only target wound infection while other healing events are left to their natural fates. Nitric oxide (NO) acts against both gram-positive and -negative bacteria and has the potential to positively affect wound healing. In this study we have developed a novel wound dressing integrated with a NO donor - S-nitroso- glutathione (GSNO) in a hybrid formulation of alginate and poly(vinyl alcohol) (PVA) to prevent/treat burn wound infection. Methods The NO releasing wound dressing was fabricated using PVA, alginate, and glycerol, crosslinked with CaCl2 incorporating GSNO. Thereafter, release kinetics were measured up to 4 days. The antibacterial efficacy was determined against both P. aeruginosa and S. aureus. Then the biocompatibility of the NO wound dressing was assessed using in vitro fibroblast proliferation and wound healing assay. Finally, the efficacy of the wound dressing was assessed in vivo using a 3-cm diameter porcine burn wound infection model. Results The Alginate-PVA-GSNO dressing showed a desired physiological level NO flux of 4.42 × 10-10 mol cm-2 min-1 for 72 hours. Alginate−PVA−GSNO dressings showed ~3 log reduction in S. aureus and ~2 log reduction in P. aeruginosa CFU/mg when compared to control. The NO-releasing dressing improved fibroblast proliferation and migration resulting in complete closure of the wound within 48 h in vitro. The safety and efficacy of NO-releasing dressing were successfully established in the both P. aeruginosa and S. aureus infected porcine burn wounds. Histological assessments are carried out to determine the effect of NO-releasing dressing on overall healing process. Conclusions This study shows Alginate−PVA-GSNO wound dressing provides antimicrobial and wound healing properties in vitro. Preliminary in vivo wound healing studies established the safety and efficacy profile of NO-releasing dressing to treat burn wounds. Applicability of Research to Practice An easy to apply, field deployable and effective antimicrobial wound dressing is still a major requisite for combat burn wounds. NO delivering alginate-PVA based wound dressing may be an ideal candidate to inhibit infection as well as promote the wound healing process.

scholarly journals Fluorescence fluctuation spectroscopy reveals differential SUN protein oligomerization in living cells

2018 ◽  
Vol 29 (9) ◽  
pp. 1003-1011 ◽  
Author(s):  
Jared Hennen ◽  
Cosmo A. Saunders ◽  
Joachim D. Mueller ◽  
G. W. Gant Luxton
Keyword(s):  
Nuclear Envelope ◽  
Living Cells ◽  
Protein Oligomerization ◽  
Linc Complex ◽  
Force Transmission ◽  
Fluorescence Fluctuation Spectroscopy ◽  
The Core ◽  
First Time

Linker-of-nucleoskeleton-and-cytoskeleton (LINC) complexes are conserved molecular bridges within the nuclear envelope that mediate mechanical force transmission into the nucleoplasm. The core of a LINC complex is formed by a transluminal interaction between the outer and inner nuclear membrane KASH and SUN proteins, respectively. Mammals encode six KASH proteins and five SUN proteins. Recently, KASH proteins were shown to bind to the domain interfaces of trimeric SUN2 proteins in vitro. However, neither the existence of SUN2 trimers in living cells nor the extent to which other SUN proteins conform to this assembly state have been tested experimentally. Here we extend the application of fluorescence fluctuation spectroscopy to quantify SUN protein oligomerization in the nuclear envelopes of living cells. Using this approach, we demonstrate for the first time that SUN2 trimerizes in vivo and we demonstrate that the in vivo oligomerization of SUN1 is not limited to a trimer. In addition, we provide evidence to support the existence of potential regulators of SUN protein oligomerization in the nuclear envelope. The differential SUN protein oligomerization illustrated here suggests that SUN proteins may have evolved to form different assembly states in order to participate in diverse mechanotransduction events.

scholarly journals Cross Kingdom Functional Conservation of the Core Universally Conserved Threonylcarbamoyladenosine tRNA Synthesis Enzymes

2014 ◽  
Vol 13 (9) ◽  
pp. 1222-1231 ◽  
Author(s):  
Patrick C. Thiaville ◽  
Basma El Yacoubi ◽  
Ludovic Perrochia ◽  
Arnaud Hecker ◽  
Magali Prigent ◽  
...  
Keyword(s):  
Mitochondrial Pathway ◽  
Stem Loop ◽  
Content Type ◽  
E Coli ◽  
Functional Conservation ◽  
The Core ◽  
First Time ◽  
Keops Complex

ABSTRACT Threonylcarbamoyladenosine (t 6 A) is a universal modification located in the anticodon stem-loop of tRNAs. In yeast, both cytoplasmic and mitochondrial tRNAs are modified. The cytoplasmic t 6 A synthesis pathway was elucidated and requires Sua5p, Kae1p, and four other KEOPS complex proteins. Recent in vitro work suggested that the mitochondrial t 6 A machinery of Saccharomyces cerevisiae is composed of only two proteins, Sua5p and Qri7p, a member of the Kae1p/TsaD family (L. C. K. Wan et al., Nucleic Acids Res. 41:6332–6346, 2013, http://dx.doi.org/10.1093/nar/gkt322 ). Sua5p catalyzes the first step leading to the threonyl-carbamoyl-AMP intermediate (TC-AMP), while Qri7 transfers the threonyl-carbamoyl moiety from TC-AMP to tRNA to form t 6 A. Qri7p localizes to the mitochondria, but Sua5p was reported to be cytoplasmic. We show that Sua5p is targeted to both the cytoplasm and the mitochondria through the use of alternative start sites. The import of Sua5p into the mitochondria is required for this organelle to be functional, since the TC-AMP intermediate produced by Sua5p in the cytoplasm is not transported into the mitochondria in sufficient amounts. This minimal t 6 A pathway was characterized in vitro and, for the first time, in vivo by heterologous complementation studies in Escherichia coli . The data revealed a potential for TC-AMP channeling in the t 6 A pathway, as the coexpression of Qri7p and Sua5p is required to complement the essentiality of the E. coli tsaD mutant. Our results firmly established that Qri7p and Sua5p constitute the mitochondrial pathway for the biosynthesis of t 6 A and bring additional advancement in our understanding of the reaction mechanism.

scholarly journals Fabrication and Characterization of an Antibacterial Chitosan/Silk Fibroin Electrospun Nanofiber Loaded with a Cationic Peptide for Wound-dressing Application

2021 ◽  
Author(s):  
Sadjad Khosravimelal ◽  
Milad Chizari ◽  
Behrouz Farhadihosseinabadi ◽  
Mehrdad Moosazadeh Moghaddam ◽  
Mazaher Gholipourmalekabadi
Keyword(s):  
Antibacterial Activity ◽  
Silk Fibroin ◽  
Wound Dressing ◽  
Treatment Strategies ◽  
High Water ◽  
Wound Dressings ◽  
Electrospun Nanofiber ◽  
Cationic Antimicrobial Peptide

Abstract Wound infections are still problematic in many cases and demand new alternatives for current treatment strategies. In recent years, biomaterials-based wound dressings have received much attention due to their potentials and many studies have been performed based on them. Accordingly, in this study, we fabricated and optimized an antibacterial chitosan/silk fibroin (CS/SF) electrospun nanofiber bilayer containing different concentrations of a cationic antimicrobial peptide (AMP) for wound dressing applications. The fabricated CS/SF nanofiber was fully characterized and compared to the electrospun silk fibroin and electrospun chitosan alone in vitro. Then, the release rate of different concentrations of peptide (16, 32, and 64 µg/ml) from peptide-loaded CS/SF nanofiber was investigated. Finally, based on cytotoxic activity, the antibacterial activity of scaffolds containing 16 and 32 µg/ml of peptide was evaluated against standard and multi-drug resistant strains of Staphylococcus aureus and Escherichia coli isolated from burn patients. The peptide-loaded CS/SF nanofiber displayed appropriate mechanical properties, high water uptake, suitable biodegradation rate, a controlled release without cytotoxicity on Hu02 human foreskin fibroblast cells at the 16 and 32 µg/ml concentrations of peptide. The optimized CS/SF containing 32 µg/ml peptide showed strong antibacterial activity against all experimental strains from standard to resistant. The results showed that the fabricated antimicrobial nanofiber has the potential to be applied as a wound dressing for infected wound healing, although further studies are needed in vivo.

scholarly journals Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 819
Author(s):  
Nicolai Rügen ◽  
Timothy P. Jenkins ◽  
Natalie Wielsch ◽  
Heiko Vogel ◽  
Benjamin-Florian Hempel ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Galleria Mellonella ◽  
Systemic Reactions ◽  
Venom Composition ◽  
Assassin Bug ◽  
Molecular Components ◽  
First Time ◽  
Tissue Digestion

Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.

Carbon dots derived from Fusobacterium nucleatum for intracellular determination of Fe3+ and bioimaging both in vitro and in vivo

2021 ◽  
Author(s):  
Lijuan Liu ◽  
Shengting Zhang ◽  
Xiaodan Zheng ◽  
Hongmei Li ◽  
Qi Chen ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Fusobacterium Nucleatum ◽  
Living Cells ◽  
First Time ◽  
Fluorescent Carbon Dots ◽  
Fluorescent Carbon

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.

scholarly journals Fe3O4@Pt nanoparticles to enable combinational electrodynamic/chemodynamic therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tong Chen ◽  
Qiang Chu ◽  
Mengyang Li ◽  
Gaorong Han ◽  
Xiang Li
Keyword(s):  
Fenton Reaction ◽  
Pt Nanoparticles ◽  
Therapeutic Modality ◽  
Ros Generation ◽  
Tumor Treatment ◽  
Superior Efficacy ◽  
Platinum Nanocrystals ◽  
First Time

AbstractElectrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O4@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe3O4@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H2O2 into ROS via Fenton reaction. In addition, Fe3+ ions released from Fe3O4@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.

scholarly journals Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Wei-Li Yang ◽  
Fang-Yuan Yang ◽  
Li Zhang ◽  
Wei-Jin Huang ◽  
...  
Keyword(s):  
Drug Development ◽  
Cathepsin L ◽  
Human Cells ◽  
New Drugs ◽  
Disease Course ◽  
Promising Target ◽  
First Time

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

scholarly journals Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jakob Weglage ◽  
Friederike Wolters ◽  
Laura Hehr ◽  
Jakob Lichtenberger ◽  
Celina Wulz ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Colorectal Carcinogenesis ◽  
Sub Saharan Africa ◽  
Interleukin 4 ◽  
Health Burden ◽  
Sub Saharan ◽  
Considerable Morbidity ◽  
First Time

AbstractSchistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

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